PNEU3 Notes

History Taking & Physical Examination

Dealing with neurology

- Is there a neurological lesion?
- Where is the lesion?
- What is the lesion?
- What investigations can confirm the diagnosis?
- What can be done to treat the symptoms & diseases?

Is there a neurological lesion?

- Minimal anatomical knowledge for clinical neurology
 Anterior & posterior circulation
 Three long tracts (longitudinal & cross-sections)
 Visual pathways
» Retrochiasmatic vs anterochiasmatic
 CSF pathway
 Cranial nerves III/IV/VI, V, VII, VIII
» Physical examination as well
 Median & ulnar nerves
 Femoral & sciatic nerves
» Myopathy?
- Additionally
 Cross-sections of the midbrain, pons & medulla
 Functional organisation of the cerebral cortex, basal ganglia & cerebellum

Where is the lesion?

History
- Description must be chronological
 Onset most important
- Mode of onset
 Hyperacute – abrupt onset: in seconds  minutes
» Vascular
» Trauma
» Seizures
 Acute – rapid onset; in minutes  hours
» Vascular
» Hypoglycaemia
» Intoxication
 Subacute – less brisk than above in hours  days
» Demyelination
» Metabolic coma
» Infections (recruitment of white cells takes time)
» Ciguatoxin intoxication (peripheral paralysis)
 Gradual – slow but apparent progress in months
» Parkinson’s disease
» Tumours
 Insidious – inconspicuous progress in years
» Hereditary
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 » Degenerative disorders
- Course of illness must be traced
 Progressively better
» Recent stroke
» Uncomplicated meningitis
 Progressively worse
» Space-occupying lesion
» Motor neuron lesion
 Intermittent
» Associated with general baseline of worsened condition
» Migraine
» Epilepsy
» Multiple sclerosis (worse after hot bath)
 Persistent
» Tension headache
» Previous trauma
» Old stroke

Examination
- Identify upper motor neuron or lower motor neuron
- Upper motor neuron (cerebral cortex  anterior horn cell)
 Cortex
 Subcortical (basal ganglion)
 Brainstem
 Spinal cord
- Lower motor neuron (anterior horn cell
 muscle)
 Anterior horn cell (spinal cord)
 Nerve root
 Plexus
 Peripheral nerve
 Neuromuscular junction
 Muscle

Analysis of weakness
Site of lesion Signs
Upper motor neuron
Cerebral hemisphere Hemiparesis & sensory impairment
Homonymous hemianopia
Dysphasia (left hemisphere) or hemineglect (right hemisphere)
Brainstem Hemiparesis or tetraparesis & sensory impairment
Often with other brainstem symptoms such as diplopia, vertigo, dysarthria
or dysphagia
Cranial nerve signs which are “crossed”
Spinal cord Bilateral weakness (tetraparesis or paraparesis)
Sensory level
Sphincter disturbance
Lower motor neuron
Anterior horn Segmental weakness (usually multiple & bilateral)
No sensory loss at all
Often with muscle fasciculation
Root or plexus Segmental weakness (multiple for plexus lesion)
Sensory loss in dermatome (but pain in myotome)
Appropriate reflex loss
Peripheral nerve confined Mononeuropathy: weakness & sensory loss the distribution of the affected

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to nerve Polyneuropathy: distal weakness & areflexia; glove & stocking sensory loss
Neuromuscular junction Fatiguable weakness
No sensory loss
Muscle Proximal weakness
No sensory loss

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Headache & facial pain

Facial pain
Cause Site Duration Treatment
Trigeminal neuralgia Unilateral, Occurs in bouts Carbamazepine
maxillary/mandibular Phenytoin
Migrainous neuralgia Unilateral, Occurs in bouts Ergotamine
ocular/cheek/forehead Sumatriptan
Atypical facial pain Bilateral/unilateral Constant Antidepressants
(e.g. amitriptyline)
Temporomandibular Unilateral, angle of jaw, On chewing Prosthetic device
arthritis cheek Surgery

Headache
- Headaches are referred pain to the surface of the head
- May result from pain stimuli arising inside or outside the cranium

Intracranial headache

Headache of meningitis
- Meningitis causes inflammation of all the meninges (pain-sensitive covering
the brain)
- Can cause extreme headache referred over the entire head

Alcoholic headache
- A headache usually follows an alcoholic binge
- Alcohol may directly irritate the meninges

Extracranial headache

Eye disorder
- Difficulty in focusing eyes may cause tonic contraction of ciliary muscles in an attempt to gain clear
vision
 Causes headache behind the eyes (retro-orbital headache)
 May cause reflex spasm in various facial & extraocular muscles that also causes headache

Nasal disorder
- Infection or irritative processes of the nasal structure cause retro-orbital headache or headache to
the frontal surfaces of the forehead & scalp

Muscular spasm
- Emotional tension often causes many of the muscles of the head to become spastic
 Headache may be referred over the entire head

Menstrual cycle
- About 60 percent of women suffer from menstrual headaches
- Can occur prior to or during menstruation
- Related to the ever-fluctuating oestrogen levels during menstrual years
 Sex hormones could influence the activity of neurochemicals important for headache,
including 5-hydroxytryptamine (5-HT)

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Migraine headache
- ~80% common
 No aura
- ~20% classical
 With aura
- Aura is usually a visual disturbance that precedes the
headache e.g. zigzag lines or blind spots

Pathophysiology

Vascular theory
- Biphasic change in cerebral blood flow with ~30%
reduction preceding the premonitory aura, followed by
a highly variable increase of similar magnitude
- Headache often begins before vasodilator phase

Neurogenic theory
- 5-HT receptors important to migraine pathogenesis/treatments
 5-HT2A
 5-HT1D
 5-HT1F

Prophylactic treatment of migraine

5-HT2 antagonist
Drugs Comments
Pizotifen Commonly used
Adverse effects include weight gain, antimuscarinic effects
Cyproheptadine Also has antihistamine & calcium antagonist actions, sometimes used in
refractory cases
Methysergide Effective, but can cause retroperitoneal fibrosis and renal failure, so not generally
used

Non-specific drugs
- -adrenoceptor antagonist: propranolol
- Tricyclic antidepressants: amitriptyline
- Calcium channel blockers: Dihydropyridines
- 2-adrenoreceptor agonists: clonidine

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Treatment for acute attack of migraine

5-HT1 agonists
- Activation of 5-HT1D receptor causes vasoconstriction & helps to restore normal
vascular tone during migraine
- Ergotamine
 Effective but often causes severe side effects
 Nausea, vomiting
 Excessive use may lead to vasospasm & paradoxically, headache
 Contraindicated in
» Pregnancy
» Ischaemic heart disease
» Peripheral vascular disorders
- Sumatriptan
 First selective 5-HT1D receptor agonist specifically designed for the treatment of migraine
 Second-generation triptan drugs include
» Nartriptan
» Eletriptan
» Frovatriptan
» Almotriptan
» Avitriptan
 All are vasoconstrictors, thus contraindicated in patients with vascular disease
 Possible mechanisms of action of triptan drugs
» Direct constriction of intracranial blood vessels (via 5-HT1D receptors)
» Inhibit neuropeptide release from sensory nerve endings (via 5-HT1D and possible 5-
HT1F receptors)
 Inhibit neurogenic
inflammation
 Decrease in the relay of nociceptive
information from the vasculature to the
brainstem (via inhibition of neuropeptide
and/or glutamate release)

Other drugs
- Analgesics such as aspirin, paracetamol, and
ibuprofen are often helpful in controlling the pain
- Rarely, parenteral opioids may be needed in
refractory cases
- Parenteral metoclopramide may be helpful for
patients with very severe nausea & vomiting

Inhibitors of cerebral vascular dilatation

- EP4 antagonists
 CJ-023423 and BGC20-1531
 Block PGE2-induced vasodilatation
- CGRP antagonists
 Olcegepant (BIBN4096)
 Telcagepant (MK-0974)
 Block CGRP-mediated vasodilatation
- Nitric oxide synthase (NOS) inhibitors
 NG-methyl4-arginine hydrocholaride (546C88)
 GW273629
 Block NO-mediated vasodilatation

Inhibitors of cerebral nerve activation

- Glutamate receptor antagonists
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  LY293558, an AMPa/kainite glutamate receptor antagonist
 LY466195, a kainite receptor antagonist
 Inhibit glutamate-mediated excitatory neurotransmission
- Transient receptor potential vanilloid receptor-1 (TRPV-1) antagonists
 SB-705498
 Blocks TRPV1-medicated release of neuropeptides (including CGRP) to prevent pain
transmission & neurogenic vasodilatation & inflammation

Types of chronic headaches

Migraine Chronic tension type Cluster headache
headache (CTTH)
Site, severity, One side (~60%) Mostly both sides One side
character Severe Mild to moderate Periorbital
Pulsatile Dull Severe
Duration 4 – 72 hours 30 minutes – 7 days (may 15 – 120 mins
go on for weeks)
Associated features Aura (e.g. visual, Depression Tears
sensory); duration: 15 –
30 mins
Nausea or vomiting Panic disorder Nasal stuffiness
Photo/phonophobia Insomnia Horner’s syndrome
(sympathetic activation)
Fibromyalgia
Age & gender 10 – 40, F > M >20, F > M Mean age 25, M > F
Family history Common Occasional Rare
Precipitants Foods, stress, rest, Stress Nocturnal
menses

Associated symptoms
Physical findings Differential diagnoses
High temperature Meningitis, encephalitis
High blood pressure Hypertensive encephalopathy
Weight loss Intracranial tumour, chronic infection
Neck stiffness, Kernig’s sign Meningitis
Impaired cognition, confusion Encephalitis, frontal lobe tumour
Oculomotor nerve palsy Posterior-communicating artery aneurysm
Abducens nerve palsy or papilloedema Raised intracranial pressure/hydrocephalus, EBV
Reduced consciousness or asymmetric motor Intracranial pathologies e.g. haemorrhage, space
weakness occupying lesion

Other chronic headache causes

- Sinusitis – pain around maxillary area, worse after cough/sneezing & associated with chornic nasal
discharge
- Dental pain – teeth/gum pain
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 - Analgesic (caffeine withdrawal headache)
- Trigeminal neuralgia – sharp & worse by chewing/eating
- Drugs – e.g. vasodilating drugs (nitrate) in IHD
- Cervical spondylosis – neck pain with radiation to occipital area

Investigations
Provisional diagnoses Investigations
Migraine, CTTH, cluster headache None
Intracranial haemorrhage/tumour/raised ICP Cerebral imaging (CT, MRI)
Meningitis, encephalitis Cerebral imaging
Lumbar puncture
Other septic work-up (blood culture, CXR)
Electroencephalogram
Giant cell arteritis ESR
Temporal artery biopsy
Cervical spondylosis Neck x-ray
Sinusitis X-ray of sinuses

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Neuromuscular Diseases

Upper motor neuron & lower motor neuron weakness

UMN LMN
No muscle wasting (except ‘disuse) Muscle wasting (except myopathy)
No muscle fasciculation Fasciculation (especially anterior horn cell)
Weakness in ‘pyramidal’ pattern: extensor of UL & Weakness in related myotome or nerve innervation
flexors of LL
Tone: spastic (increased) Tone: hypotonic (lax)
Reflex: brisk Reflex: reduced or absent
Plantar reflex: toe upgoing Plantar reflex: toe downgoing
Associated sensory pattern: Associated sensory pattern: according to
‘Hemi’ if cortical dermatome or nerve distribution
Truncal sensory ‘level’ if cord
Gait: hemiplegic if cortical or ‘scissoring’ if cord Gait: ‘high-stepping’ if foot drop of ‘waddling’ if limb-
girdle weakness

Pattern of weakness
- Anterior horn cell
 Prominent fasciculation
 Myotome weakness
 No sensory loss (tongue fasciculation in motor neuron disease)
- Root
 Asymmetrical
 Myotome weakness
 Associated dermatome loss
 Pain common
- Plexus
 Asymmetrical
 Weakness/sensory loss in apparent ‘multiple roots’
 Signs of local causes e.g. trauma, irradiation, tumour
- Nerve
 Asymmetrical
 Weakness/sensory loss in named nerve distribution
- Polyneuropathy
 Symmetrical
 Usually distal worse ‘glove & stocking’ distribution
- Neuromuscular junction
 Proximal
 No wasting
 Fatigable weakness
 Normal tendon reflex
 No sensory loss
- Muscle
 Proximal
 Usually no wasting
 Normal tendon reflex
 No sensory loss

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Dermatomes & Myotomes

Common lesions at each level of lesion

Anterior horn cell Motor neuron disease
Nerve roots Compression by discs
Osteophytes
Plexus Thoracic outlet syndrome,
Injured by trauma,
Post-irradiation injury,
peripartum phases
Peripheral nerves Entrapment
Mononeuritis multiplex
Neuromuscular junction Myasthenia gravis
LETS
Muscles Polymyositis
Myopathy

Neurpathy (distal involvement) Myopathy (proximal involvement)

Clinical features Positive sensory symptoms (burning, No sensory symptoms
parasthesia – tingling/pins & needles,
hyperalgesia
Negative sensory symptoms (impaired sensory Weakness
“numbness”)
Weakness
Physical signs Defomirties (e.g. wrist drop, claw hand, pes Myopathic facies
cavus)
Wasting may be present Wasting – mainly observed in
hereditary conditions
Weakness – usually distal Weakness – usually proximal
[except for certain conditions e.g.
myotonic dystrophy, inclusion body
myositis]
Hyporeflexia Normal tendon reflexes
Pattern of sensory impairment: No sensory loss

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 1. dermatomal-lesion at nerve root(s)
2. Restricted to a particular peripheral nerve
(e.g. median ulnar nerve)
3. Glove & stocking - polyneuropathy
Remarks Fasciculations is not a characteristic
feature of myopathy. Mainly present
in anterior horn cell disease

Investigations for neuromuscular disease

- Nerve conduction study (NCS)
- Electromyography (EMG)

Anterior horn cell disease

Motor neuron disease

- Amyotrophic lateral sclerosis in USA
- Fatal clinical condition of unkonw etiologies in which motor neurons of voluntary muscles die
progressively
- Typically combination of UMN & LMN (in pattern of myotomes) deficits
- No sensory loss
- Usually present with
 Focal limb weakness (limb-onset, ~80% of faces)
 Dysphagia (bulbar onset, ~20%)
 That are progressive & spreading
- Fasciculations of involved muscles (tongue, limbs)
- Extraocular muscles typically spared
- Reflexes are brisk

Neuromuscular junction disorder

Myasthenia Gravis
- Autoimmune disease
- Anti-acetylcholine receptor antibodies – against post-synaptic acetylcholine receptors
 Block the binding of Ach to receptor
 Destruction of Ach-R and postjunctional fold
- Anti-MuSK Ab (Muscle specific tyrosine kinase antibody)
 MuSK protein is a tyrosine kinase receptor
- Clinically manifested as fatigue & weakness with diurnal variation
 More severe in the afternoon or after exercise
- Can be restricted to ocular muscles (ocular MG) or affect other parts of body (generalised MG)
- Diagnosis confirmed with
 Tensilon test (edrophonium – acetylcholinesterase inhibitor)
» Alleviate ptosis or ophthalmoplegia
 Ice pack-test (cooling inhibit acetylcholinesterase activity)
 Repetitive nerve stimulation (>10% reduction in amplitude)
 Anti-bodies assay

Lambert-Eaton Myasthenic Syndrome

- An immune-mediated disorder characterised by reduced release of Ach from the presynaptic
terminal
- Ig-G antibodies directed against presynaptic voltage-gated calcium channel (VGCC-Ab)
- Interfere with calcium-dependent release of Ach
- Resulting in reduced endplate potential on the postsynaptic membrane
- Decreased NMJ transmission failure
- Result in proximal muscle weakness
- Tendon reflexes may be initially reduced, but increased after intense exercise (facilitation)
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 - Etiology
 Autoimmune
 Paraneoplastic (classically small cell carcinoma)
- Diagnosis confirmed with
 Repetitive nerve stimulation
 Antibody assay

Mononeuropathy
- Neuropathy affecting a single peripheral nerve (E.g. median nerve, radial nerve, ulnar nerve)
- Most common condition
 Carpal tunnel syndrome

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 T1

Cranial space occupying lesions

- Mass lesion within the cranium
- Depending on location this may exert mass
effect
 Displacement of normal structures
away from itself T2
 Alteration of shape or contour of
adjacent structures
- Distinguishing cranial SOL 1 2
 T1 weighted sequence
» Fluid is dark (CSF)
 T2 weighted sequence
» Fluid is bright (CSF)
» Globe is bright
- Mass effect
 Effacement of adjacent sulcal spaced by
displacing the CSF in the sulci (1)
» Sulci aphasement – loss of fluid in the
sulci
 Ipsilateral ventricular structures compressed by 3 4
a mass making it smaller than the contralateral
counterpart (2)
 Midline shift (3)
» Normal midline structures shifted
towards the contralateral side
 Hydrocephalus (4)
» Accumulation of CSF in the ventricular
system

Clinical features
- Raised intracranial pressure (ICP)
 Headache
 Nausea/vomiting
 Blurred vision
 Impaired consciousness
- Focal neurological deficits
 Hemiparesis
 Dysphasia
 Patterns of visual field loss (hemianopia)
 Cognitive & memory deficits

Tumours of the CNS

- Not just one tumour
- Histologically benign tumours can potentially damage as a space occupying lesion by raised
intracranial pressure
- Histologically benign tumours can cause functional neurological problems
- Malignant tumours do not metastasise usually outside the brain
- Classification
 Gliomas
» Diffuse astrocytomas
» Pilocytic astrocytoma
» Oligodendrogliomas
» Ependymomas
» Choroid plexus tumours
 Meningiomas
 Primary CNS lymphomas

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  Others

Gliomas
- Except pilocytic astrocytomas, all
gliomas should be treated as potentially
malignant
- Except pilocytic astrocytoma, they all
transform from a low-grade form to a
high-grade lesion within years
Diffuse astrocytoma
Diffuse astrocytoma
- Poor identification tumour
 Infiltrative
- Basis of histologic features, they are stratified into 3 groups
 Well-differentiated astrocytoma (grade II/IV)
 Anaplastic astrocytoma (grade III/IV)
 Glioblastoma (grade IV/IV)
 With increasingly grim prognosis as the grade increases
- Well-differentiated astrocytomas are poorly defined, gray,
Anaplastic astrocytoma
infiltrative tumours that expand & distort the invaded brain
without form a discrete mass
 Infiltration beyond the grossly evident margins is always present
- Glioblastoma multiforme (GBM) is the commonest primary brain tumour
 Prognosis with treatment
GBM at corpus
» GBM: a year
callosum –
» Anaplastic astrocytoma: 2 butterfly lesion
years
» Fibrillary astrocytoma: 5 –
7 years
Glioblastoma
- In glioblastoma, variation in the gross
multiforme – rim
appearance of the tumour from region to GBM - mitosis
enhancement
region is characteristic
 Some areas are firm & white, GBM – extreme pleomorphism
others are soft & yellow (result of
tissue necrosis)
 Still others show regions of cystic
degeneration + haemorrhage
- Glioblastoma has a histologic appearance
similar to that of anaplastic astrocytoma,
as well as either necrosis or vascular GBM - necrosis
proliferation

Pilocytic astrocytomas
- A benign childhood astrocytic tumour
- Well circumscribed
- Cystic change
GBM – glomeruloid endothelial proliferation Pilocytic
Pilocytic astrocytoma – Pilocytic astrocytoma
- Cerebellum astrocytoma
bipolar spindle cells in 3rd ventricle
- Cerebrum
- Third ventricle

Oligodendrogliomas Cerebellar cyst

- Slow growing tumour of adult

cerebrum
 Mostly frontal/temporal
lobes
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 - Characteristic calcification on neuroimaging
- Potentially malignant
- Most cases transform to anaplastic oligodendroglioma within 7 – 10 years
- Patients may have had several years of antecedent neurologic complaint, often Oligodendrogliomas –
including seizures typical calcifications
- Patients with oligodendrogliomas enjoy a better prognosis than that for patients
with astrocytomas of similar grade
- Treatment
 Surgery
 Chemotherapy
 Radiotherapy
- Well-differentiated oligodendrogliomas (WHO grade II/IV) are infiltrative
tumours that form gelatinous, gray masses that may show
 Cysts
 Focal haemorrhage
 Calcification calcification Clear vacuolated
cells
- Well-differentiated oligodendrogliomas on microscopic
examination, composed of
 Sheets of regular cells with spherical nuclei
containing finely granular-appearing chromatin
- Tumour typically contains a delicate network of
anastomosing capillaries
- Anaplastic oligodendroglioma (WHO grade III/IV) is a
more aggressive subtype with
 Higher cell density
 Nuclear anaplasia oligodendrogliomas
 Mitotic activity

Ependymomas Ependymomas – tumour lines

- Tumour of childhood or young people the 4th ventricle
- Spinal cord or IV ventricle
- Low grade malignant
 Most cases transform to
anaplastic ependymoma 5 – 7
Ependymomas – commonest
years
tumour of spinal cord
 Prognosis similar to fibrillary
astrocytoma

Choroid plexus papilloma

Choroid plexus papilloma Choroid plexus papilloma

Hydrocephalus

Papillomatous tumour

Medulloblastoma
- Primitive tumour, commonest brain tumour of childhood
- Brain tumour: commonest solid cancer in children

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 - Cerebellar location
- Tendency to spread via CSF, and
also to bones + extraneural sites
- 60 – 80% survival rate now Hydrocephalus
with combination of
 Surgery
 Chemotherapy Typical
 Radiotherapy location
in vermis
Meningiomas
- Extracerebral (extra-axial) Medulloblastoma
tumour at
 Brain surface Medulloblastoma
 Para-sagittal region
 Spinal cord
 Skull base
- Meningiomas may infiltrate
skull & appear as extracranial
or subcutaneous scalp mass
 This does not make it a
malignant tumour
- Benign tumour
Meningothelial whorls Meningioma at the spinal canal
- About 10 – 15%
recurrence
- Vague non-
localising
symptoms or
with focal findings referable to compression of adjacent brain
- Multiple meningiomas, especially in association with eighth-nerve
schwannomas or glial tumours points towards the diagnosis of
neurofibromatosis type 2 (NF2)

Primary cerebral lymphomas

- Primary CNS lymphoma, occurring mostly as diffuse large B cell
lymphomas, accounts for
 2% of extranodal lymphomas Primary cerebral lymphomas
 1% of intracranial tumours
- Most common CNS neoplasm in immunosuppressed persons
 Tumours are nearly always positive for the oncogenic
Epstein-Barr virus
- Non-immunosuppressed populations, age spectrum is relatively wild
 Incidence increasing after 60 years of age

Germinoma
- Commonest germ cell tumour of the brain
- Same as dysgerminoma of ovary and seminoma of testis
- Tendency to spread via CSF
- Highly sensitive to radiotherapy
 90% cure rate

Pituitary adenoma
- Commonly regarded as a “brain” tumour though in fact it is not
- Produce visual, pressure or endocrinological symptoms
- Non-functioning (produce hypopituitarism)
- Prolactinoma
- Acromegaly

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 - Mixed Growth hormone-prolacin
- Cushing’s disease (microadenoma)
- Others

Other tumours GH – secreting pituitary adenoma in

- Vestibular schwannoma (acoustic acromegaly – looks like the acidophilic
neuroma) at cerebellopontine (CP) cells of normal pituitary gland
angle Metastatic lymphoma/leukaemia
- Arteriovenous malformation Vestibular schwannoma
at meninges
- Cerebellar hemangioblastoma
- Craniopharyngiomas
- Germinoma
- Metastatic lymphoma/leukaemia
at meninges
- Cerebral metastases

Unique of brain tumours Arteriovenous malformation

- Insidious onset
- Progressive (contrast stroke &
head injury)
- Headache
 Worst in the morning
(lying down  venous
congestion)
 Aggravated by coughing
Cerebral metastases
& straining
- Known primary cancer
- Familial syndromes
 Haemangioblastoma
 Neurofibromatosis I & II
 Li-Fraumeni syndrome
 Tuberous sclerosis
 Turcot syndrome
Craniopharyngiomas – heavily calcified,
benign but locally infiltrative tumour
Cerebellar hemangioblastoma
- significant morbidity & recurrence rate

Management
- To acquire a working diagnosis
 Glioma
 Meningioma
 Metastasis
- Role of steroid (dexamethasone 4mg qds)
- Treatment modalities
 Expectant  biopsy  surgical debulking and/or complete excision  adjuvant therapy
(radiotherapy & chemotherapy)
- Investigational treatments
 Gene therapy
 Immunotherapy
 Traditional Chinese Medicine

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Brain abscess
- Pyogenic abscess = cerebritis progressing to focal necrosis with capsular
formation
Brain abscess:
Causes
marked vasogenic
- Haematogenous dissemination oedema
 IV drug abuse
 Generalised septicaemia
 Pneumonia
 UTI
- Direct extension
 Paranasal sinusitis
 Otomastoiditis
- Penetrating trauma or surgery
- Crptogenic/idiopathic

Location
- Haematogenous spread of infective agents & metastases
 Seeds at grey/white junction
- Direct extension
 Around entry site

Features
- Plain CT
 Low attenuation lesion
 Slightly hyperdense rim (capsule forms in 10 –
14 days)
 Surrounding oedema (vasogenic oedema)
 Mass effect

- Contrast enhanced CT
 Ring enhancement Brain abscess: contrast Brain abscess: plain CT
CT
 Oedema & ring enhancement suppressed by
steroid
Brain abscess:
 Smooth, thin wall contrast CT
» Compared with thick wall for
metastases
- MRI
 Central high signal intensity due to liquefaction
on T2W images
 Hypointense rim (collagenous capsule) on T2W
images
 Perifocal oedema with high T2 signal
 Ring enhancement

Brain abscess vs. brain tumour

- Thin smooth capsule
- Thin smooth ring enhancement
- T2W hypointense capsule
- Other MRI techniques
 Diffuse weighted imaging (DWI)

Complications
- Daughter abscesses
- Ventriculitis

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  Rupture of inflammatory contents into ventricular system

Unique of brain abscess

- Very similar to brain tumours
- Fever: only in 50% of the patients
- Convulsions: more common (30 – 50%) than in brain tumours
- Primary focus of infection can be identified in 80%
 Haematogenous versus contiguous spread
 Pyogenic versus granulomatous (e.g. tuberculosis)
 Single bacterium versus mixed growth

Management
- Surgical
 Aspiration of abscess (or excision) to establish tissue &
microbiological diagnosis
 Re-tapping of abscess may have to be carried out
- Role of steroid
- Appropriate antibiotics: 6 – 8 weeks
- Management of primary focus of infection

Hydrocephalus
- Excess CSF due to imbalance between CSF formation & absorption resulting in increased
intraventricular pressure (IVP)
- Normal CSF flow
 Choroid plexus (lateral ventricles)
 3rd ventricle
 Aqueduct of Sylvius
 4th ventricle
 Foramena of Luschka (x2) & Magendie
 Subarachnoid CSF Non-communicating hydrocephalus
 Arachnoid villi Mass lesion in basal ganglia
 Dural venous sinuses compressing 3rd ventricle

Non-communicating hydrocephalus
- Blockade of CSF flow within the ventricular system
with ventricular dilatation proximal to the
obstruction
- Disproportionate dilatation of ventricles up to the
obstructive site
- Example: extrinsic compression by tumour
- Colloid cyst
 Dense on CT Non-communicating
hydrocephalus:
 Developmental lesion colloid cyst
 Block outflow to lateral ventricles
 Patients appear very sick
- Green arrows: Transependymal migration of CSF
into brain parenchyma
 Suggests ACUTE worsening
 Herniatin g into brain parenchyma –
hydrocephalus has occurred suddenly

Communicating hydrocephalus
- Elevated IVP secondary to blockade beyond the 4th
ventricular outlet within the subarachnoid pathways
- Symmetric dilatation of all ventricles
- Example: obstruction at arachnoidal granulation in subarachnoid haemorrhage
19 Joyce Kwan
 Inferior horns of lateral
ventricles prominent
- CSF spaces can be prominent as well - Density in sylvian fissure &
- Types subarachnoid space of the 4th
ventricle & around the brain-
 Obstructive (common) stem
» Reduced CSF absorption at - Due to acute subarachnoid
arachnoid granulations haemorrhage
» Post subarachnoid haemorrhage - Inflammation in lesions or
blood perforating into
» Meningitis
arachnoid granulations
» Protein in CSF from tumours causing obstruction
 Non-obstructive (rare)
» Normal pressure hydrocephalus in
elderly
» CSF overproduction (rare)
 Choroid plexus papilloma
» Impaired venous drainage (rare)
 Previous extensive venous sinus thrombosis
» Congenital absence of arachnoid granulations (very rare)

Unique of hydrocephalus
- Insidious onset
- Non-specific symptoms & lack of focal deficits
- Triad of symptoms
 Dementia
 Gait disturbance
 Incontinence of urine
- Primary causes
 Tumour obstruction
 Inflammation (e.g. SAH, meningitis)
 Idiopathic (e.g. normal pressure hydrocephalus)
 Congenital (e.g. Chiari malformation)

Management
- Obstructive hydrocephalus
 Removal of primary obstructive lesion (e.g. tumour excision)
 Endoscopic III ventriculocisternostomy
 Last resort: VP shunt
- Communicating hydrocephalus
 Repeated LPs
 Lumbo-peritoneal shunt
 Ventriculo-periotneal shunt
 Ventriculo-atrial shunt (last resort)

Investigations
- Review of history & physical exam
- Imaging
 Skull X-ray
 CT
 MRI
- Lumbar puncture
 Indications & more importantly its contraindications
 Safe
» Opening pressure
» Cell counts
» Glucose & protein
» Microbiology

Intra-axial or extra-axial

20 Joyce Kwan
 Intra-axial metastases:
hyperdense masses with
surrounding hypodense
- Intra-axial: within the brain (neural – axis) Vasogenic oedema (spares
expanding it cortical grey matter)
- Extra-axial: outside the brain compressing it - Fluid accumulating in the
sulci
Intra-axial
- Associated skull lesion uncommon
- Brain cortex displaced toward skull
- Gyral broadening Intra-axial haematoma: acute
- Variable post-contrast enhancement haematoma (<1 week):
- Common intra-axial masses hyperdense & surrounding
 Metastases (lung primary cancer commonly vasogenic oedema
associated with the brain) Vasogenic oedema:
 Intracranial haematoma accumulation of fluid within
 Primary intracranial tumours white matter cells

 Brain abscesses
 Infarcts: have mass effects

Extra-axial
- Broad base in contact with dura/bone
- May have bony abnormality
- Brain cortex displaced away from skull &
compressed
Meningioma – hyperdense Dural blood supply – gaining
- Solid masses: typically marked advancing mass
enhancement enhancement from dual blood
supply
 No blood brain
- Dural feeding arteries Extra-axial
- Common meningioma:
overlying skull is
 Extradural/subdural haematoma slightly thickened on
 Meningioma the right
- Less common - hyperdense – mass
 Metastases effect
 Neuroma Vasogenic
 Dermoid/epidermoid cyst oedema
 Subdural empyema (children)

Left MCA infarct Multiple

Location (acute – subacute) meningiomas:
- Many intracranial lesions extra-axial in
location; around
have a definite petrous temporal
Cytotoxic oedema
predilection for specific involves grey & bone & falx
locations white matter: cerebri
- Anatomic location of CNS irreversible cell
lesions is useful in death – associated
with infarcts
suggesting differential - causes necrosis of
diagnosis
Neurocysticerosis
- Example
(old): multiple dense
 Cerebellopontine angle mass (CPA) small intra-axial
» Schwannoma (acoustic neuroma) calcifications with no
» Meningioma mass effect
» Epidermoid - late stage parasitic
infection
- Calcification equal to
Tissue characteristics overlying skull base
- Density (CT)/signal intensity (MRI)
- Calcification
- Cavitation/necrosis

21 Joyce Kwan
 - Haemorrhage
- Enhancement pattern

Mass effect for neurologic emergency

- Brain herniation Subfalcine herniation
 Subfalcine (falx cerebri)
 Transtentorial (through tentorium)
» Compression of midbrain
 Tonsillar (foramen magnum)
- Compression of important anatomical structures Uncal herniation –
 Pituitary tumour with suprasellar extension compressing the compression
optic chiasm with visual loss towards midbrain
- Mass effect causing obstructive hydrocephalus
 Cerebellar medulloblastoma
» Obliterating 4th ventricle/aqueduct causing obstructive hydrocephalus

Coronal MRI Extra-axial

Lateral ventricles haematoma:
(grossly dilated) (T1W)
shallow can
still cause
brain Uncal herniation
herniation
3rd ventricles
Compression
(grossly dilated)
Cerebellar of midbrain
tonsillar
Cerebellar herniation
(can crush Dilatation of temporal horn
medulloblastoma
brainstem of left lateral ventricle
– enhancing mass
causing (hydrocephalus)
death)

22 Joyce Kwan
Infections of CNS
- CNS infection is a neurological emergency
 Delay in diagnosis & treatment can often lead to permanent neurological deficit or death
- CNS infections are suggested by constellation of signs & symptoms
 Supported by laboratory studies
- Classification
 Meningitis (meningeal involvement)
» Purulent
» Lymphocytic
» Granulomatous
 Abscess (focal pus collection in brain parenchyma)
» Brain
» Epidural
» Subdural (empyema)
 Encephalitis/meningoencephalitis (parenchymal  meningeal involvement)
» Mostly viral infection
» Bacterial/TB or fungal infection are uncommon causes
» Consider autoimmune causes
 NMDA encephalitis if occurred in young patients with negative viral workup
 Myelitis
 Spongiform encephalopathy

Entry of organism in CNS

Virus
- Viruses usually gain entrance into the host by penetration of mucosa, skin, gastrointestinal or
urogenital barriers
- Viral replication occur near the site of entry  secondary viraemia
- Access to CNS is achieved by
 Haematogenous spread – cross blood brain barrier
 Neuronal spread – retrograde axonal transmission
» Rabies
» Herpes simple virus
» Varicella-zoster virus
» Poliovirus

Bacteria, TB, Fungal & parasite

- Many organisms responsible for meningitis have a particular ability to adhere to mucus membranes,
thus promoting entry into host’s blood
- Organisms may gain access to CNS by
 Haematogenous dissemination  cross blood brain barrier
 Direct spread of organisms from infected pericranial structures, such as sinuses, middle ear,
mastoid

Clinical features
- General
 Subacute onset of
» Fever
» Headache
» Altered mental state
» Malaise
- Specific features (may overlap)
 Meningitis
» Meningism (classic triad of fever, neck stiffness & altered mental state)
 Though classical; sensitivity is only 44%
» Other features – photophobia
23 Joyce Kwan
  Encephalitis
» Characterized by cerebral dyfunction
» Cognitive impairment (limbic system involvement)
 Acute memory disturbance
» Behavioural changes
 Disorientation
 Hallucination
 Psychosis
 Personality changes
» Focal neurological deficit
 Hemiparesis
 Cerebellar dysfunction
 Aphasia
» Seizures
 Brain abscess
» Depends on location of abscess, may cause focal neurological dysfunction or seizures
 Raised ICP
» Headache
» Nausea
» Vomiting
» Blurred vision (papilloedema)

Relevance of history for risk factors

- Immunocompromised patients – opportunistic infection
 Patients with malignancy
 Patients with immunosuppressive agents (steroid, chemotherapy)
- Occupation
 Butcher – strep. Suis
- Travel history
 China – TB, HIV
 Asia – Dengue fever, Japanese B encephalitis
 USA, Canada – Eastern Equine virus, St. Louis encephalitis, West Nile virus
- Contact history
 TB patients – TB
 Sexually transmitted – HIV, syphilis
 Insect or mosquito bites – Arbovirus, Flavivirus (dengue fever, Jap B)
 Animals – rabies, leptospirosis, lyme disease (rare in HK)

Meningitis
- Meningeal infection involving leptomeninges (arachnoid & pia mater) and subarachnoid space
- Acute meningitis: onset of meningeal symptoms over few hours up to several days
- Chronic meningitis: insidious onset of meningeal signs & symptoms over weeks
 CSF remain abnormal for >4 weeks
- Mostly caused by viral infection
 Most common: enterovirus (e.g. coxsachiviruses)
 Echovirus
 Arboviruses (US)
 Usually less severe as compared to bacterial meningitis
- Can also be caused by
 Bacterial infection
 TB
 Fungal infection
 Usually more clinically severe, higher incidence of
death & complication
 Meningitis caused by S. Pneumoniae
» Results in 20 – 30% of hospital mortality and
up to 40% of intracranial complications (e.g.
24 Joyce Kwan
 hydrocephalus, deafness etc)
» 30 – 50% of survivors have permanent neurological sequelae
Clinical factors Common pathogens
Neonates E. Coli
Group B haemolytic strep.
Listeria monocytogenes
Children < 14 years old H. Influenza
Strep. Pneumoniae
Neisseria Meningitidis
Adults & Young children Strep. Pneumoniae
Neisseria Meningitidis
TB
Elderly immunocompromised Strep. Pneumoniae
Listeria monocytogenes
Gram negative bacilli
Pseudomonas
TB
Cryptococcus
Skull fracture or externally communicating Mixed bacterial infection
dural fistula or parameningeal source of
infection (otitis, sinusitis)
After surgical procedures Enterobacteriaceae
Hospital acquired infection Staphylococci
Gram negative bacilli
Pseudomonas

Symptoms
- Severe headache
- Stiff neck
- Photophobia
- Fever/vomiting
- Drowsy & less responsive/vacant
- Rash (develops anywhere on body)

Acute bacterial meningitis

- Purulent meningitis
- Pyogenic organism
- Spread from bloodsream meninges
- Direct spread from middle ear infection, sinuses, open skull fracture
- Purulent exudate in leptomeninges with acute inflammatory infiltrate (neutrophils)

Epidemiology
- Incidence 2 – 3/100,000
- Peak in infants & adolescents
- Risk groups
 Hereditary immune defects (e.g. complement components)
 Splenic dysfunction
 T-cell defects (e.g. HIV, malignancy)
 Basal skull fracture
 Middle ear disease/chronic otitis media
 Cranial trauma, CSF shunts
- Incidence: 1.27/100,000 population

25 Joyce Kwan
Streptococcus pneumoniae
- Normal resident of human nasopharynx in
~20% of population
- Gram positive cocci in pairs, capsulated
- Polysaccharide capsule is virulence factor
(evade phagocytosis)
- Type specific antibody protective
- > 90 different serotypes in 46 serotypes
based on their polysaccharide capsule
- 10 – 15 serotypes account for most (>80%) paediatric invasive
pneumococcal disease worldwide
- Pneumococcal disease manifestations (highest – lowest)
 Otitis media
 Pneumonia
 Bacteraemia
 Meningitis

Pneumococcal meningitis
- Seen in infancy, elderly & immunosuppressed
- Highest mortality, 15 – 20%
- Associated with
 Sinusitis
 Skull fracture
 Pneumonia
 Otitis media
- Complications
 Cerebral oedema
 Cranial nerve palsies (e.g. deafness, mental
retardation)
- Treatment
 Cefotaxime IV until organism’s sensitive available
 Benzylpenicillin IV if sensitive
 Vancomycin + rifampicin
- Prophylaxis
 Protein conjugate vaccines (PVC-7, -10, - 13)
available

Pneumococcal vaccination risk groups recommendation

- Children < 2 years of age, with or without additional
at-risk conditions
- Persons age > 65 years, with or without additional at-
risk conditions
- Persons age between 2 – 65 with following at-risk
conditions
 History of invasive pneumococcal disease
 Immunocompromised states
» Asplenia, HIV, primary immunodeficiency
» Immunodeficiencies related to malignancies and
transplantation
» Immunodeficiencies related to use of
immunosuppressive drugs/systemic steroid
 Chronic disease
» Chronic cardiac, pulmonary, liver or renal disease
» Diabetes mellitus or CSF leakage
 With cochlear implants

26 Joyce Kwan
Meningococcal infection
- Neisseria meningitides, fastidious gram-negative diplococcus
 Groups A, B, C, Y, W135
- Reservoir from human nasopharynx
- Affects all ages, commonly young adults
- Rapid progression
- Typical presentation
 Abrupt onset
 Very rapid progression
 Meningitis
 Sepsis
 Rash (may appear late)
» Presence of rash means that immediate medical treatment is vital
» Bacteria multiply in blood vessels and release toxins which damage the
vessel wall, resulting in leakage of blood underneath the skin
» Rash starts as purple blood spots, which spread rapidly into bruises
- Complications
 Meningococcaemia with vascular collapse shock & bilateral adrenal
haemorrhages
 Adult respiratory distress syndrome (ARDS)
 Disseminated intravascular coagulation (DIC)
 Acute renal failure (ARF)
 Intestinal bleeding
 Liver failure
 Central nervous system dysfunction
 Acute myocarditis & heart failure
 Death
- Early treatment with 3rd generation cephalosporin or benzylpenicillin can be life-saving
- Treatment
 Benzypenicillin IV, 14 days
 Cefotaxime if resistant
- Prophylaxis
 Rifampicin to eradicate nasopharyngeal organisms in close contacts include
» Household contacts
» Nursery school
» Military camps contacts
 Not necessary for medical personnel unless intimate contact
 Vaccines to serogroups A, C, Y, W135 available

Waterhouse-Friederickson syndrome
- Meningococcaemia
- Overwhelming sepsis
- Endotoxic shock
- Disseminated intravascular coagnulation
- Widespread vasculitis
- Organ necrosis & haemorrhage
- Acute bilateral adrenal glands haemorrhage
- Adrenocortical insufficiency

Haemophilus influenzae meningitis

- Infants 1 month - <3 years
- Pleomorphic gram-negative rod, capsular type b
- Pre-existing
 Otitis media
 Pharyngitis
 Pneumonia

27 Joyce Kwan
 - Complications
 Cerebral oedema
 Hydrocephalus
 Cranial nerve palsies (e.g. deafness: 2 – 3%, mental retardation)
- Treatment
 Cefotaxime IV until organism’s sensitivity available
 Ampicillin IV if sensitive (10 – 30% ampicillin resistant due to plasmid carrying -lactamase
gene)
- Prophylaxis
 Close contacts should be given rifampicin 4 days
 Hiv vaccine available

Streptococcus suis
- Gram positive cocci in short chains
- Butchers, abattoir workers
- Incidence in HK ~0.2/100,000 population
- Serotype 2 or streptococcus group R (or S)
- Manifestations
 Septicaemia
 Meningitis
 Infectious arthritis
- High incidence of deafness associated with meningitis
- Treatment
 High dose IV benzylpenicillin 14 – 21 days

Chronic meningitis
- Insidious onset of meningeal signs & symptoms over weeks
 CSF remains abnormal for > 4 weeks
- Aetiological agents
 Mycobacterium tuberculosis
 Cryptococcus neoformans
 Treponema pallidum
 Amoeba (naegleria fowleri)
 Human immunodeficiency virus

Granulomatous meningitis
- Mycobacterium tuberculosis
- Basal involvement
- Insidious onset of
 Confusion
 Headache
 Fever
- Mononuclear meningeal exudate
- CSF blockage  hydrocephalus
- Often primary TB in lungs

Cryptococcal meningitis
- Cryptococcus neoformans
- Habitat: soil rich in pigeon excreta
- Exogenous infection via inhalation of yeasts
 Yeasts engulfed by alveolar macrophages
- HIV patients, immunocompromised
 Spreads to lymph nodes  bloodborne  organ, CNS
- Space-occupying lesions with granulomas & mucinous exudate
- Grey matter around ventricles and basal ganglia
- Cerebral white matter
28 Joyce Kwan
 - Cerebellar dentate nucleus
- Infection of meninges seed to arachnoid space & CSF

Predisposing factors
- Underlying cellular immunodeficiency (AIDS)
- Malignancy (lymphoma)
- Corticosteroid therapy
- Collagen vascular disease e.g. SLE
- Diabetes mellitus
- Alcoholism

Signs & symptoms

- Indolent & protracted
- Headache – frontal, temporal, retro-orbital
- Weight loss
- Low grade fever
- Mental aberrations
- Evidence of increased intracranial pressure
- Cranial nerve or motor abnormalities
- Cerebellar signs

Diagnosis
- Samples: CSF, blood
- CSF opening pressure increased
- Direct examination
 Yeast with large capsules in India ink
- Culture
 Culture on sabouraud without cycloheximide
- Serology
 Detection of capsule antigen titre in CSF & serum by latex agglutination test
» Monitors treatment response

Treatment
- IV amphotericin B (+ flucytosine)
- Life-long fluconazole prophylaxis following primary treatment (in AIDS patients)

Neuronal injury in meningitis

Nasopharyngeal colonisation

Local invasion & bacteraemia

Meningeal invasion

Bacterial replication in subarachnoid space

Release of bacterial cell wall, LPS

Macrophages
Cerebral microvascular endothelium

Increased blood brain barrier permeability

IL-1, TNF
Subarachnoid space inflammation
Vasogenic oedema Increased CSF outflow resistance
Hydrocephalus Cerebral vasculitis Cytotoxic
Interstitial oedema Cerebral Infarction oedema

29 Joyce Kwan
Differential diagnoses
- Acute meningitis
 Bacterial
Cereb
 Viral ral
 TB blood
 Fungal
- Brain abscess
- Rickettsial infection, leptospirosis, parasitic
causes etc.
- Non-infective e.g. subarachnoid
haemorrhage
- Malignancy

Laboratory investigations for meningitis

- Lumbar puncture for CSF
 Opening pressure
 CSF for cell count, protein & glucose level
 Gram smear  acid fast stain, India ink for Cryptococcus
 Bacterial culture
 Rapid DNA detection of mTB, viral studies
  Latex agglutination for common bacterial antigens
  Latex agglutination for Cryptococcus antigens
  Viral studies & culture
- Plasma glucose
- Blood cultures
- Serology for viral studies, throat swab & stool culture if viral etiology
suspected

Procedure of lumbar puncture

- Perform CT brain before LP to rule out large SOL and extensive odema which
are contraindications for LIP
 Risk of transtentorial herniation
- Aseptic technique
- Site preparation (iodine & alcohol)
- Needle (#18)
- Interspace L4/L5
- Opening pressure
- Appearance
- Collect CSF
- Send immediately to laboratory

CSF Interpretations
Appearance Cells (per ml) Type of cells Protein (g/L) Glucose
(mmol/L)
Normal Clear <4 Lymphocytes 0.15 – 0.45 2.8 – 4.2 (60%
(L) plasma glucose)
Bacterial Cloudy  Polymorphs (P) > 0.5 < 2.2 (usually
<0.1 – 1.1)
Viral Clear  L>P > 0.5 Normal
Tuberculosis Opalescent  L>P > 0.5 < 2.2 (1.1 – 2.2)
Encephalitis Clear  L > 0.5 Normal
Subarachnoid Xanthochromic  Crenated RBCs > 0.5 Normal
haemorrhage (yellow)
: 15 – 100 cells/ml
: 100 – 2000 cells/ml
30 Joyce Kwan
Diagnostic criteria for bacterial meningitis
- Increase cell count > 80% polymononuclear cells strongly suggestive, but not diagnostic
- Increase protein, little diagnostic significance
- Decrease glucose due to increase glucose consumption & decrease glucose transport to brain
- Gram’s stain of CSF sediment
 Meningococcus less commonly seen
 H. Influenzae misread as pneumococcus
- Culture of CSF & blood

Management of meningitis

Bacterial
- Give empirical treatment as soon as possible
 3rd generation cephalosporin
 Benzl penicillin
- High dose needed to penetrate the BBB
- Beta-lactam allergy  vancomycin
- Suspected penicillin—resistant  vancomycin + 3rd generation cephalosporin
- Suspected listerial meningitis  ampicillin + 3rd generation cephalosporin
 Elderlies
 Immunosuppressed
 Signs of brainstem encephalitis
 Pregnant ladies
- Dexamethasone should also be given shortly before/with the first dose of antibiotics
 Reduces neurological complication
- Prophylaxis of bacterial meningitis
 Temporary nasal carriage occurs frequently with N. Meningitidis
 Prophylactic antibiotics should be considered in close contacts of patients with N.
Meningitidis to eliminate nasal carriage
 Choice of antibiotics
» Rifampicin
» Ceftriaxome
» Ciprofloxiacin
» Azithromycin

Viral
- Most common: acyclovir
 Herpes simplex virus
 Varicella zoster virus
- In immunocompromised, consider
 Ganciclovir – cytomegalovirus (CMV)
 HAART (Highly Active Antiretrovirus Therapy) – HIV

Encephalitis/meningoencephalitis
- Encephalitis: inflammation of the brain resulting in decreased mental state e.g. confused or stupor,
early in course of disease with minimal meningeal signs
 Meningoencephalitis: meningeal signs plus altered consciousness (parenchymal  meningeal
involvement)
 Drowsiness
 Confusion
 Abnormal behaviour
 Coma
- Mostly viral infection
- Bacterial/TB or fungal infection are uncommon causes
- Consider autoimmine causes

31 Joyce Kwan
  Anti-NMDA (N-methyl D-aspartate/glutamate) receptor encephalitis if occurred in young
patients with negative viral workup

Aetiological agents
- Virus (most common cause)
 Human-to-human transmission
» HSV (usually type 1, type 2 more common in newborns)
» VZV
» EBV
» Measles
» Mumps
» Rubella
» HIV
 Animal/inset vectors
» Mosquitoes (dengue fever, Jap B encephalitis, West Nile virus, Eastern Equine virus)
» Ticks (Arboviruses)
» Mammals (rabies)
- Bacterial
 Mycoplasma
 Rickettsial infection (rare)
- Parasites
 Toxoplasmosis
 Neurocysticercosis
 Trichinosis
- Spirochetes
 Syphilis
 Leptospirosis
 Lyme disease
- Fungi
 Cryptococcus
 Candidiasis
 Aspergillosis
- Protozoal
 Malaria
 Amoebiasis
 Toxoplasmosis

Herpes Simplex Encephalitis

- Most common cause of sporadic fatal encephalitis
- Mostly caused by HSV-1
 In neonates, can be caused by HSV-1 or 2
- May be due to reactivation of latent HSV in situ within the CNS
- In most cases, necrosis occurs in the temporal lobe, with characteristic MRI & EEG features
- Diagnosis by PCR with CSF
- Anti-viral treatment reduces mortality from 70% - 20%
 Acyclovir
- Nearly 2/3 of survivor shave residual neurological deficit

Skin rash
- Singles
 Cluster of painful vesicles in right T3 dermatome in varicella
zoster virus infection
- Oral herpes
 Most often caused by HSV type 1
 Can also be caused by HSV type 2
- Herpetic whitlow around fingernail by HSV type 1 (60%) or 2 (40%)
32 Joyce Kwan
MRI brain

- Herpes simple encephalitis – right temporal lobe involvement on MRI

Complications of meningoencephalitis
- Transtenorial herniation
 Caused by diffuse swelling of the brain or
hydrocephalus
- Hydrocephalus
 Results from basal obstruction of CSF
- Infarcts
 Caused by inflammatory occlusion of the basal arteries
- Seizure
 Caused by cortical inflammation
- Focal neuronal injury
 E.g. deafness
- Circulatory collapse
 Particularly meningococcaemia
- Hyponatraemia due to SIADH

Myelitis
- Inflammation of the spinal cord
- Occur with/without encephalitis
- Transverse myelitis
 Stimulates acute transection of spinal cord
 Rostral limb weakness
 Sensory loss
 Loss of bowel & bladder control
- Ascending myelitis
 Ascending flaccid paralysis & rising sensory deficit
 Early bowel & bladder involvement
- Poliomyelitis
 Involves anterior horn cells of spinal cord
 Flaccid paralysis & muscular pain without sensory loss or bladder dysfunction

Brain abscess
- Focal pus collection in brain parenchymal
 May have mixed aerobic & anaerobic organisms
- Mostly caused by bacterial, fungal or TB infection
- Usually secondary to trauma or pus collection elsewhere
 Sinusitis
 Dental infection
 Endocarditis
- Lumbar puncture not routinely needed
33 Joyce Kwan
 - Diagnosis based on Toxoplasmosis: Ring-
 Contrast CT enhancing lesion with
 MRI surrounding oedema
 Surgical aspiration
- Empirical treatment
 Combination of
» Pencillin or vancomycin
» Ceftriaxone
» Metronidazole
- Surgical drainage often needed
Neurocysticercosis:
Calcified or cystic
Opportunistic infection in HIV patients lesions with “dot”
- Toxoplasmosis inside  scolex
- Neurocysticercosis & Calcifications in
- Progressive multifocal le koencephalopathy, PML (JC virus) muscles on X-rays
- Cryptococcal meningitis
- CMV encephalitis
- TB meningitis
- Syphilis

Confirm diagnosis of CNS infection

- Bacterial & viral studies
- Blood culture for febrile patients
- Lumbar puncture PML: Periventricular
white matter non-
 Opening pressure
enhancing lesion
 CSF appearance – clear vs. turbid
 Cell count, differential count
 Protein, glucose (compared to serum level)
 Gram stain, bacterial culture, Indian ink
 Viral study may support or rule out major treatable viral infections (i.e. HSV, VZV, CMV, HIV)
» Polymerase chain reaction
» Viral titre
 Fungal culture & detection of cryptococcal antigen for fungal infection
- Optional investigations
 Nasopharyngeal aspirate if seasonal influenza or swine flu suspected
 Serology – cryptococcal antigen
- Imaging
- Electroencephalogram
 If patient present with seizure
 Helpful in diagnosing certain specific infection
» HSV encephalitis
» CJD have characteristic features

CNS findings in lumbar puncture

Normal Viral Bacterial TB/cryptococcal
meningitis/meningoencephalitis meningitis
Colour Clear Clear Often turbid Often turbid
Pressure  18  18  18  18
(cmH2O)
WCC <5 10 – 1000 100 – 10,000 10 – 10,000
(mm3) Lymphocyte predominant Neutrophils Lymphocyte
predominant predominant
Protein 0.2 – 0.45 – 0.8 0.5 – 2.0 0.5 – 3.0
(g/l) 0.45
CSF/serum > 0.5 > 0.5 < 0.5 < 0.5
glucose
34 Joyce Kwan
 - Neutrophilic response to tuberculous meningitis is known with acute onset & in HIV patients
- Lymphocytic pleocytosis in acute bacterial meningitis is seen in cases who
have already been partially treated with antibiotics

Imaging
- Brain imaging (contrast CT brain, MRI brain) to assess extent of CNS
involvement & associated complications
 Meningitis: meningeal enhancement
» TB & cryptococcal meningitis: frequently have skull base HSV encephalitis – temporal
involvement lobe involvement
 Encephalitis in brain parenchyma:
» HSV encephalitis:
increased signal in medial
temporal lobe & inferior
frontal lobe Brain abscesses
» TB encephalitis: presence
of tuberculoma
 Abscess: typically ring-enahncing
lesion with contrast
 Hydrocephalus
 Cerebral oedema
 Cerebral infarction &
haemorrhage
- Chest X-ray – pulmonary TB
- X-ray limbs – calcification of neurocysticercosis

Electroencephalogram
- Used if patient present with seizure Neurocysticercosis:
- Helpful in diagnosing certain specific infection CT brain (right): multiple calcifications
MRI brain (left): cystic lesion with
 HSV encephalitis & CJD have characteristic features surrounding oedema

35 Joyce Kwan
Infections of the Nervous System: Paediatric Aspect
- Prevalence of causative bacterial agent depend on age group
- Streptococcus pneumoniae & H. influenzae are the most common organisms in healthy children
- In neonates, Group B streptococcus is the most common etiological agent
 E. Coli
 Listeria Monocytogenes
 Gram negative organisms
- > 3 months
 S. Pneumoniae
» Mechanism of resistance of S. Pneumoniae to penicillin
 Related to encoding a new penicillin-binding protein (PBP) with reduce
affinity to beta-lactam antibiotics
 PBP is an important enzyme participating in cell wall synthesis by inhibiting
mucopeptide formation
 Resistance mechanism can be overcame by increase the dose of beta-lactam
antibiotics
 H. Influenzae
» Beta-lactamase producing
 N. Meningitidis

Meningitis

Epidemiology
- Incidence
 H. Influenzae: 2/100,000
 N. Meningitidis: 4 – 5/100,000
 S. Pneumoniae: 2.5/100,000
- Overall
 H. Influenzae: 45%
 S. Pneumoniae: 18%
 N. Meningitidis: 14%
- 1 months – 4 years
 H. Influenzae most predominate
- 5 years onward
 N. Meningitidis

Pathogenesis
- Bacterial colonisation in nasopharynx
 3 common meningeal pathogens colonise the nasopharynx mucosa in 5 – 40% of children
- Offending agents enter the CNS through
 Haematogenous route
 Direct invasion
- Generation of inflammation within the subarachnoid space
 Transmigration of neutrophils across the endothelia into the CSF
- Induction of neuronal and auditory cell damages
- Bacterial cell wall and membrane elements stimulate the release of various inflammatory cytokines
- After antibiotic administration, rapid cell lysis causes the release of cell wall and membrane
fragments
- Augment further inflammatory cascades
 Role of corticosteroid in managing bacterial meningitis

Clinical aspects
- Symptoms of bacterial meningitis depend somewhat on the sage of the patients and the duration of
illness
- Young children
 Fever
36 Joyce Kwan
  Irritable (unexplained irritability despite lack of fever)
 Nausea, vomiting
 Seizures
 Lethargy
- Older children
 Fever
 Headache, neck pain
 Vomiting
 Photophobia
 Seizure
 Altered mental status

Signs
- Signs more subtle in young children
- Lethargy, alerted conscious state
- Bulging fontanelle indicating increased ICP (neither highly sensitive nor specific)
- Meningism (more common in children > 12 – 18 months)
 Kernig sign – positive when thigh is bent at the hip & knee at 90 & subsequent extension in
the knee is painful  resistance
 Brudzinski sign – appearance of involuntary lifting of legs when lifting a patient’s off the
examining couch when the patient lying supine
- Cranial nerve palsies
 6th nerve palsy
- Focal neurological signs
 Hemiparesis
 Results of an infarction
- Others
 Petechial or purpuric rash in N. meningitidis meningitis

Lumbar Puncture
- Lumbar puncture remains the most important early diagnostic test
 CSF
» Cell counts & differentials
 WBC: >1000/mm3 with polymorphs predominant
» Gram stain and culture
» Protein
» Glucose (need paired with plasma glucose level)
» Polysaccharide antigen testing by latex agglutination
 CSF in children older than 6 months old contains < 6 WBCs/mm3 with no polymorphs
 CSF in newborn can be up to 22 WBC/mm3 with 60% polymorphs
 Protein concentration elevated (mean 100 – 200 mg/dL)
 CSF-serum glucose ratio <0.6
- Contraindications for lumbar puncture
 Critically ill children with hypotension, respiratory distress
» Positioning for lumbar puncture can further compromise ventilation & circulation
 Profound thrombocytopenia/deranged clotting profile
 Evidence of increased intracranial pressure
 Focal neurological signs
» Increased ICP  CT scan before relieving pressure or else leads to coning of the brain
 Infected overlying skin

Monitoring
- Blood culture
- Complete blood picture
 Differential white cell count
- Acute phase reactant

37 Joyce Kwan
  C-reactive protein
- Electrolytes

 SIADH as a complication of bacterial meningitis

- Clotting profile
 Monitor for DIC

Management
- Bacterial meningitis is a medical emergency
- Neurological morbidity and mortality relate to the timing of the initiation of antibiotics
- Even a few hours’ delay will greatly affect prognosis adversely
- Empirical antibiotic coverage
Patient group Antibiotics
< 1 month Ampicillin + aminoglycoside/broad spectrum cephalosporin
1 – 3 months Ampicillin + broad spectrum cephalosporin
3 months – 18 years Broad spectrum cephalosporin (vancomycin)
 Ampicillin: 200 – 400 mg/kg/day IV Q6H
 Cefotaxime: 200 – 300 mg/kg/day IV Q8H
 Vancomycin: 60 mg/kg/day IV Q6H
- Increasing prevalence of resistant strains of S. Pneumoniae
- 35 – 40% of all isolates recovered from cultures of usually sterile body fluids were resistant to
penicillin
- Vancomycin & cefotaxime/ceftriaxone are recommended as initial treatment for children older than
1 month of age with definite or probable bacterial meningitis
- S. Pneumoniae
 Need to determine the MIC (minimal inhibitory concentration) of pencillin and
cefotaxime/ceftriazone
 Penicillin-susceptible strain (MIC < 0.06g/ml)
» Penicillin G
 Penicillin-nonsusceptible (MIC > 0.1g/ml) but cefotaxime/ceftriazone susceptible (MIC <
0.5g/ml)
» Cefotaxime or ceftriazone
 Penicillin-nonsusceptible (MIC > 0.1g/ml) and cefotaxime/ceftriazone non-susceptible (MIC
> 1g/ml)
» Vancomycin + cefotaxime/ceftriazone
 Second lumbar puncture 24 – 48 hours afterward in all penicillin-nonsusceptible cases
» To document CSF sterility after antibiotic treatment
- H. Influenzae
38 Joyce Kwan
  Cefotaxime or ceftriaxone
- N. Meningitidis
 Penicillin G
- Recommendations for repeat lumbar puncture at 24 – 48 hours
 All neonates
 Penicillin-nonsusceptible S. Pneumoniae meningitis
 Lack of clinical improvement in 24 – 48 hours after starting antibiotics
 Prolonged or secondary fever
 Immunocompromised hosts
- Guideline for duration of antibiotic therapy
 S. Pneumoniae: 10 – 14 days
 H. Influenzae: 7 – 10 days
 N. Meningitidis: 7 – 10 days
- Role of dexamethasone
 Inflammation has an important role in the pathophysiology of bacterial meningitis
 A meta-analysis of randomised controlled trials performed since 1988 showed beneficial
effect of adjunctive dexamethasone in children
» Decrease severe hearing loss in HiB meningitis
» Also effective in decreasing severe hearing loss in S. Pneumoniae meningitis
- In adults
 Early treatment with dexamethasone
» Reduce the risk of unfavourable outcome
» Reduce the risk of death
» Most beneficial groups are the groups with GCS 8 – 11 and GCS 3 – 7 on admission
 Dexamethasone has beneficial effects when given at the same time or slightly before the first
dose of antibiotic

Encephalomyelitis

Etiology
- A 20-year survey of children with encephalitis aged 1 month – 16 years old
- Extensive microbiological investigations
 Viral antigen detection and cultures in CSF
 CSF:serum antibody ratio
 Viral isolation from other sites
 Paired serum antibody titres
- In patients aged 1 – 9 years old
 40% unknown causes
 Direct infections
» Enterovirus infections: 10%
» Herpes simple: 8%
 Post-infection
» Varicella-zoster virus
» Respiratory pathogens
 Influenza A, B
 Parainfluenza 1, 2, 3
 Adenovirus
- HSV encephalitis is a treatable cause
 10% of all cases of viral encephalitis
 HSV type 1 account for 95% of cases
» Primary or reactivation of HSV infections
 Clinical presentation difficult to differentiate from other etiological agents

Investigations
- EEG findings
 Paroxysmal lateralising epileptiform discharges
- Imaging
39 Joyce Kwan
  MRI is more sensitive than CT
» Involvement of temporal lobe
 Oedema associated with focal infection or haemorrhagic necrosis is evident
- Definitive treatment
 Acyclovir 45 mg/kg/day Q8H for 21 days
 Shorter duration of therapy associated with relapse

Conditions mimicking encephalitis

- Toxic encephalopathy
 Reye syndrome
 Acute toxic ingestion
- Inborn error of metabolism
 OTC deficiency
- CNS vasculitis
 SLE
- Tumour
 Brainstem glioma
- Others
 Intracranial haemorrhage

40 Joyce Kwan
 Gunshot Injury

Head Injury
- Types of head injury
 Missile injury
 Penetrating injury
 Crush injury
 Deacceleration injury
Linear fracture
Pathology

Skull fractures
- Linear (“bursting”) fracture
- Depressed (“bending”) fracture
 Usually comminuted fracture
- Fracture of skull base
 Often indicates severe head injury
» Torn dura mater  leakage of CSF
 Otorrhoea
 Rhinorrhoea
 Pneumatocele
 Difficulty of visualisation in plain X-ray
- Fatal head injuries do not always have a fracture Acute
 The brain is more important than the skull subdural
haematoma
Traumatic Haematomas

Subdural Haematoma
- Acute subdural haematoma
 Most common & important
 Haematoma compressing on underlying brain
 Bridging veins on the surface of the brain
ruptures causing accumulation of blood
within the subdural space
- Chronic subdural haematoma
 Cause of dementia
- Complications
 Subfalcine herniation of frontal lobe
 Midline shift Epidural haematoma
 Uncal herniation, compressing brainstem
» Major compression results in coma
 Unresponsive & dilated pupils
due to compression of ciliary
muscle
 Central tentorial herniation, compressing
cerebellum
 Tonsillar herniation through foramen
magnum, compressing medulla
» Unchecked supratentorial pressure 
downward displacement of brainstem
& cerebellum
» Perforating branches of the posterior
circulation of Circle of Willis are stretched

Epidural haematoma
- Lucid interval
- Neurosurgical emergency

41 Joyce Kwan
 - Fracture of temporal bone causing rupture of the
middle meningeal artery
- Blood will accumulate in epidural space causing
emergency

Primary injuries to the brain

Contusions

- Cerebral (contusional) haematoma

 Causes bruises on the surface of
the brain
- “Contrecoup” – opposite the area of
impact
- Contusions usually happen when people
fall backwards thus
 Frontal & temporal lobes
usually affected (contrecoup
area)
Contusions at bases of
- Many bony prominences in the anterior both frontal & temporal
& middle cranial fossa lobes
- Lacerations

Diffuse axonal injuries

- White matter injury
- Commonest cause of prolonged
comatose state in head injury
- Haemorrhagic lesions in torn corpus
callosum and dorsal brain stem
- White mater tracks also torn  small
haemorrhagic lesions in brainstem
- Commoner in rotational type of injury
- Frequent absence of other mass lesions
- Axonal balls histologically

Secondary injuries to the brain

- Cerebral swelling (oedema)
 Raised ICP  impede blood
flow
- Hypoxia/ischaemia
- Associated injuries
- Convulsions

Clinical management
- Assess comatose status: Glasgow coma
scale
- Reduce cerebral swelling
- Evacuate mass lesion
- Prevent hypoxia/hypercapnia
- Close monitoring of raised intracranial pressure

Imaging
Linear fracture
X-ray
- Linear fractures
 Asymmetrical

42 Joyce Kwan
 Depressed
 Straight or abrupt angles fracture
 Do not branch
 No sclerotic margin
 Scalp haematoma
- Depressed fracture
 Bone displaced into cranium
 May appear as an area of sclerosis

CT scan – Multi-detector CT
- Patient supine scan in the axial plane Soft tissue window
- Reconstruct into any plane
 Coronal
 Sagittal
 Oblique
- Different windows to enhance different structures
 Soft tissue window
 Bone window
- Interpretation
 Isodense (gray) Bone
window
» Normal brain parenchyma
 Hypodense (black or dark gray)
» Air, fluid (CSF), fat
» Many pathological processes
 Hyperdense (white)
» Acute haemorrhage
» Bone & calcification
» Foreing bodies
» IV contrast (not usually required for trauma)

Mass effect
- Midline shift
Linear fracture
- Compression of ventricles Depressed
- Brain herniation fracture

Four main pathologies

- Fractures
- Epidural haemorrhage
- Subdural haemorrhage
- Cerebral contusion
- (Subarachnoid haemorrhage)
- (Intracerebral haematomas)

Fractures
- Linear fracture
 Asymmetrical
 Straight
 Scalp haematoma
 Important if they cross
» Middle meningeal artery
» Dural sinus
» Paranasal sinuses
Compound fracture
- Depressed fracture – External
 Bone displaced into the cranim

43 Joyce Kwan
  X-ray not usually done in paediatric
patients since CT has to be done to confirm
anyway
» Thus if clinically suspicious 
directly CT
- Compound fracture
 External Compound fracture –
 Internal internal
» Base of skull fractures
 Axial > coronal Epidural Epidural
» Look for fluid levels in haemorrhage: haemorrhage
 Sphenoid sinus supratentorial
 Middle ears
 Mastoid air cells

Epidural haemorrhage
- 90% associated with a fracture
- Caused by damage to major vessels
 Middle meningeal artery
 Dural sinuses
- Early brain herniation & compression of
brainstem Epidural
haemorrhage:
- Hyperdense
infratentorial
- Biconvex Epidural
- Adjacent to fracture haemorrhage
- Cannot cross the sutures (coronal & lambdoid)
- Can cross falx cerebri & tentorium
- 90 – 95% supratentorial
- 5 – 10% infratentorial
- Worse if >2 cm or > 1.5cm with mid line shift
- Focal hypodense area in the hyperdense
haemorrhage suggest active arterial bleeding
 Fresh blood  fluid (dark)
 Swirling effect (old & new blood mixing)
- Can increase in size so low threshold for repeat
scan

Subdural haemorrhage
- Tears of cortical bridging veins & small venous
sinuses
- Crescent shape
- Can cross the sutures (coronal & lambdoid) but
can not cross the falx & tentorium
- Acute (<1 week)
Acute subdural
 Hyperdense haematoma
- Subacute (1 – 3 weeks)
 Isodense
 Easy to miss
 Beware of patients who are
» Old
» Alcoholics
 They may have no definite history of head
injury
- May be bilateral
 Bifrontal subdural haemorrhage may be Subacute subdural
Subacute haemorrhage
easily missed
subdural
haemorrhage
44 Joyce Kwan
  Bilateral frontal & temporal lobe contusion risk factors
» Liver cirrohosis
» alcoholic
- Chronic (>3 weeks)
 Hypodense Bifrontal
subdural
Cerebral contusion haemorrhage
- Bruises of the brain
- Coup or contracoup
- Most commonly frontal & temporal
 Classically: bifrontal & bitemporal contusions
- Hypotension
- Oedema
- Necrosis
- Mixed
 Hypodense (oedema & necrosis)
 Hyperdense (foci of haeorrage)
- Haemorrhage may be delayed Cerebral Chronic subdural
contusion haemorrhage
Intracerebral haematomas
- Usually caused by penetrating injury such as bullets

Subarachnoid haemorrhage Intracerebral Cerebral

haematomas contusion
- 11%
- Very young & old
- Complication is hydrocephalus
- Beware of patient with a lot of blood, they may have
ruptured an aneurysm and then had the head injury

Diffuse axonal injury

- Diffuse axonal injury
 Trauma the rotational injury
- Axonal disruption may be seen as small haemorrhage on imaging (MRI > CT)
- Damages
 Peripheral white matter
 Corpus callosum
 Upper brain stem
- High morbidity & mortality

Clinical management
Diffuse axonal injury
- Aims
 Concept of 2nd brain insult
 Intracranial pressure (ICP)/Cerebral perfusion pressure (CPP) / Cerebral blood flow (CBF)
» Consequence of raised ICP
 Recognise the main CT pattern of head injury (HI)
 Principles for management of raised ICP
 Principles for management of open HI
 Risk factors in minor HI

Head injury
- Causes
 Road traffic accidents
» Driver
» Passenger
» Pedestrian
» Cyclist
45 Joyce Kwan
  Fell from height
 Slip & fell
 Hit by falling objects
 Assault
 Gun shot
 Sport
- Types of head injury
 Close/open
 Diffused/focal
» Diffuse: diffuse axonal injury
» Focal: brain contusion, epidural/subdural haematoma
 Scalp injury
» Laceration
 Skull: fracture
» Vault, base
» Linea, depressed

Skull base fracture

SXR/CT evidence Clinical features
Direct Indirect Haemorrhage CSF leak Cranial
nerve palsy
Anterior Paranasal Epistaxis, periorbital Rhinorrhoea I, II-IV
fossa sinus fluid bruise (raccoon eyes)
level
Middle Mastoid Intracranial Bleeding from ear, Otorrhoea VII, VIII
fossa Fracture air cell air Haemotypanum,
line fluid level Retromastoid bruise
(battle sign)
Posterior Occipital bruise
fossa

Primary & secondary brain insult

- Primary
 Damage to nervous structure, blood vessels or both at time of injury
 Focal injury Intracranial haematoma Mass effect Focal deficit
» Contusion/laceration
 Diffuse injury
» Diffuse axonal injury Brain oedema  Intracranial Pressure
- Secondary
 Sequel of the primary insult, leading to
further brain damage & neurological  Cerebral Perfusion Brain shift
deterioration Pressure (CPP)
 Intracranial  Cerebral Blood flow Brain herniation
» Haematoma (CBF)
 Epidural
Cerebral Ischaemia Brainstem compression
 Subdural
 Intracerebral
» Brain oedema
» Seizure
» Infection:
meningitis/abscess
» Hydrocephalus
 Extracranial
» Hypoxia
» Hypotension

46 Joyce Kwan
 - Key management in the acute stage of head injury is to prevent/treat secondary brain insult

Intracranial pressure
- Monro-Kellie doctrine
 Rigidity of the cranial vault
 Incompressibility of the intracranial constituents
» Change in volume of the brain  reciprocal change in volume of one of the other
components
- Total craniospinal volume = blood + CSF = parenchyma (intracellular
& extracellular parts)
- Increase in intracranial pressure
 Decrease cerebral blood flow
 Herniation
» Tentorial (uncal herniation)
 Decrease conscious level
 Unequal pupils
 Contralateral UMN signs
» Foramen magnum (tonsil herniation)
 Respiratory failure
 Decerebration
» Subfalxial herniation

Autoregulation
CPP MAP−ICP
- CBF = CVR = CVR
- CPF = cerebral blood flow
- CPP = cerebral perfusion pressure
- MAP = mean arterial pressure (diastolic pressure
1
+ 3 pulse pressure)
- CVR = cerebral vascular resistance
 Vessel diameter
 Viscosity

Initial Management of head injury

- Depends on the severity & speed of recover, a HI patient may go through the following phases:
 Pre-hospital
» At the spot
» Transportation
 Acute hospital
» A&E
» Operation
» ICU/HDU/ward care
 Convalescent/rehabilitation hospital
 Home
- Initial assessment
 A – airway
» Patent
» Risk of aspiration
 B – breathing
» Adequate spontaneous breathing
 C – circulation
» Shock is not typical feature of intracranial pathology
» Look for internal blood loss/spinal injury
 D – disabling neurological deficit
- Active scalp bleeding can lead to shock
 Should be stopped by suture rather than bandage

47 Joyce Kwan
 - Look for multiple injuries especially in unconscious patient

History
- Mechanism of injury
- Precipitating factor
 Convulsion
 Syncope
 Stroke
- Events since the HI
 LOC
 Post-traumatic (retrograde) amnesia
 Lucid interval
 Convulsion
- Neurological symptoms
 Headache
 Vomiting
- Past medical, drug & allergy
- Pre-morbid functional status

Neurological examination
- Conscious level: Glasgow Coma Scale (GCS)
- Pupils & cranial nerves
- Motor power
- Reflex
- Spine injury
 Sensory level
 Anal tone
- Unequal pupil & impaired consciousness suggest transtentorial herniation

Glasgow Coma Scale (GCS)

Adult Infants & Children
Eye opening (E4) Spontaneous ---
(E3) To command To sound
(E2) To pain ---
(E1) None ---
Speech (S5) Oriented Appropriate for age, social smile
(S4) Disoriented Cries but consolable
(S3) Inappropriate Persistently irritable
(S2) Incomprehensible Restless, lethargic
(S1) None ---
Motor (M6) Obeys commands Spontaneous
(M5) Localised pain ---
(M4) Withdraws ---
(M3) Spastic flexion ---
(M2) Extension ---
(M1) None ---
- Severity of head injury
 Minor: > 13/15
 Moderate: 9 – 12/15
 Severe: < 8/15
- Important for progress & communication
- Management strategy guidance and prognosis implication
Intracranial haematoma Mortality
Minor 0.7% 0.4%
Moderate 9% 4%
48 Joyce Kwan
Severe 45% 45%

Investigations
- Depends on the severity & clinical findings
- Blood tests
 CBP
 RFT
 ABG
 Clotting profile
 Cross-match
- Imaging
 X-ray: cervical & skull
 CT brain

Indications for CT brain

- History of LOC
- Post-traumatic amnesia
- Impaired conscious level
- Focal neurological sign
- Neurological symptoms
 Headache
 Nausea
 Vomiting
- Skull fracture or penetrating head injury
- Scalp haematoma in children
- Difficult to assess due to influence of alcohol/medication
- Unknown premorbid condition

Management of closed HI
- Haematoma with mass effect
 Craniotomy
 Evacuation
 ICP monitoring
 ICU care
- Severe HI
 No mass lesion
 Airway protection
 ICP monitoring
 ICU care
- Moderate HI
 Depends on risk factors & prognosis
 May be managed as severe HI if poor prognosis
 Or minor HI if good prognosis
- Minor HI
 Clinical observation
 CT brain

Patients requiring ICP monitoring

- Risk of developing ICP
 Abnormal CT (contusion, intracranial haemorrhage)
- Severe diffuse brain injury  brain oedema
- GCS observation not sensitive enough to check progress
 Severe – moderate HI
 Patient requires sedation
- Risk of ICP monitoring

49 Joyce Kwan
Management of raised ICP in HI
- Intracranial haematoma (hours)
 Delayed haematoma
- Brain oedema (days)
 Related to breakdown of neural tissue
 Impairment of blood-brain barrier
 Loss of vascular autoregulation
 Most commonest cause & difficult to treat
- Hyperaemia (uncommon cause)
- Hydrocephalus (weeks to month)
- Intraventricular ICP monitoring
- External ventricular drainage
- Aim of control:
 ICP < 22 mmHg
 CPP  60 mmHg
- General management
 Avoid venous congestion, head up 30
 Treat pain, control agitation & fever
 Correct hypercapnia
 Maintain adequate blood pressure & volume
 Correct anaemia (Hb > 10 g/dL)
- Surgical evacuation of mass lesion
 Craniotomy
Epidural
» Bone flap is temporarily
haematoma
removed from skull to access
the brain
» Solid haematoma
» Haemorrhagic contusion
- CSF drainage of hydrocephalus
- Brain oedema
 CSF drainage
 Osmotherapy (mannitol)
 Controlled hyperventilation
(caution)
 Barbiturate therapy
 Decompressive craniectomy
» Skull flap is not immediately
replaced, allowing brain to Craniotomy for
swell, thus reducing EDH

intracranial pressure
- Hyperventilation for hyperaemia (caution)

Management of epidural haematoma

- Often associated with fracture
- Focal brain injury with good outcome Acute subdural haematoma
- Craniotomy for evacuation of clot

Management of acute subdural haematoma

- Often associated with brain contusion or
diffuse injury
- Poor outcome
- Can also behave like epidural haematoma in the old age patients
- Craniotomy for evacuation

50 Joyce Kwan
Management of diffuse axonal injury (DAI)
- White matter injury
- Mechanism: rotational/shearing force
- Prolonged comatose state
- Cognitive impairment
- Small haemorrhages in
 Corpus callosum
 Dorsal brain stem
- No mass lesions Diffuse Axonal Injury
- Can develop severe diffuse brain swellings
- May be associated with focal injury

Multitrauma
- Cervical injury: 8% of comatose head injury
patients
- Symptoms: neck pain
- Signs:
 Neck tenderness
 Deformity
 Neurological signs
- Investigations (depends on consciousness, symptoms/signs & initial investigation results)
 Cervical X-ray:
» Open mouth view
» AP view
» Lateral view (C1 – C7/T1 junction)
» Flexion/extension views
 CT cervical spine
 MRI spine

Glasgow outcome scale

- Classical outcome measure for head injury
1. Death
2. Vegetative state
3. Severely disabled
a. Not ADL-independent
4. Moderately disabled
a. Independent in ADL but not returned to work or resume normal socia life
5. Good recovery
a. Returned to work or resume normal social life

51 Joyce Kwan
Disturbance of consciousness

Definitions
- Consciousness
 Perception of inputs
 Processing of information
 Expressions of thoughts
 Verbal output
 Command following
 Eye opening
- Syncope – inability to maintain postural tone and consciousness due to lack of perfusion to the brain
- Seizure – transient occurrence of signs & symptoms due to abnormal excessive or synchronous
neuronal activity of the brain
 Abnormal, paroxysmal discharge of neurons leading to impairment of functions
- Epilepsy – disorder of brain characterized by an enduring predisposition to generate epileptic
seizures & by the neurobiologic, cognitive, psychological and social consequence of this condition
- Confusion – neurobehavioural disorder characterized by an acute mental status change, fluctuating
course and abnormal attention
- Blackout, dizziness, collapse – layman terms without stringent definitions

Syncope Seizure
Previous Cardiac diseases Febrile convulsion
predispositions Cardiac medications Family history of seizures
History of NPC with RT History of head injury
Family history of cardiac disease History of encephalitis
Previous events Yes possibly Yes possibly
Situations & triggers Trigger: Pain Trigger: Sleep deprivation
Prolonged standing, Menstrual cycle
Sudden standing or head- Intercurrent illness
turn
Emotional upheaval Flickering lights
Coughing Video games
Micturition Alcohol
Defaecation
Situation: Hot/crowded Situation: Any
Exercise (cardiac) Even sleep
Preceding symptoms Lightheadedness Aura (epigastric rising for temporal
Nausea lobe epilepsy [TLE], somatosensory
Fainting for neocortical epilepsy)
Blurring of vision
Palpitations
2nd sympathetic activation: sweating,
pallor, cold extremities
Convulsive elements Briefing jerking only Tonic/clonic elements, long
Duration Short (seconds) Long (30s to 2 minutes)
Uprolling eyeball, Less often Often
salivation, vocalization
Injury, incontinence, Less often (e.g. maybe abrasion & Often (e.g. burns injury, bone fracture,
tongue biting bruises) lateral tongue bite)
After math Quick recovery (Seconds) Clouding of consciousness
Todd’s paresis

52 Joyce Kwan
History taking
- Clues from the past
 Febrile convulsion as infant
 Family history
 History of head trauma or encephalitis
 Similar events in the past
- Precipitating events
 Sleep deprivation
 Alcohol
 Catamenial (related to menstruation) exacerbations
 Flickering lights
 Video games
- Preceding events
 Situational elements
» Waiting at bus stop
» Getting up from sitting
 Preceding symptoms
» Nausea
» Feeling o black out
» Light-headedness
» Palpitations
» Sweating
» Feeling of aura e.g epigastric rising sensation
- Event description (may be from witness)
 Up-rolling eyeball
 Tongue biting (lateral)
 Salivation
 Loss of consciousness
 Limb twitching
 Urinary/faecal incontinence
 Injury (fracture, burns)
 Duration
- Aftermath
 Post-event drowsiness
 Neurological signs
» E.g. Todd’s paresis – focal weakness in a part of the body after a seizure and usually
subsides completely within 48 hours
 Post-event headache

Physical Examination
- Higher cerebral functions
- Cranial nerve examination
- Upper limb neurological examination
- Lower limb neurological examination
- Cardiovascular, respiratory, abdominal examination
- Vitals & general observations
 Temperature
 Neurological observation
 GCS

Investigations
- Baseline blood tests
 CBP
 RFT
 LFT
 Glucose

53 Joyce Kwan
  Bone profile
 Thyroid functions
 ECG
- Imaging
 CXR
 CT brain if needed
- Special investigations
 Holter
 Tilt table test
 EEG

Differential diagnoses of transient loss of consciousness

- Blood pressure/perfusion related
 Hypotension ( postural)
 Cardioneurogenic syncope (vasovagal)
- Cardiac rhythm related
 Paroxysmal tachyarrhythmia
 Sick-sinus syndrome with significant long pause
- Drugs
 Negative inotropic or chronotrophic agents
 Blood pressure medications
- Metabolic
 Hypoglycaemia
 Severe anaemia
 Hepatic encephalopathy
 Severe uraemia
- Neurological
 TIA
» Severe posterior circulation ischaemia
 Subarachnoid haemorrhage
 Psychogenic
 Sleep disorders
 Seizures

54 Joyce Kwan
Syncope
Type of syncope Mechanism Investigations
Neurocardiogenic syncope Neutrally-mediated reflex
Vasodilatation Positive TTT with BP
Bradycardia drop > 20 mmHg &
Vasovagal syncope Neurocardiogenic syncope in younger patients bradycardia
Situational syncope When associated with cough, micturition
Carotid sinus syndrome Exaggerated baro-receptor reflexes leading to Carotid massage may
bradycardia & hypotension (older patients) theoretically
reproduce syncope
Orthostatic hypotension Autonomic dysfunction impairs normal Postive TTT with BP
vasoconstriction response to fall in BP drop > 20 mmHg but
normal heart rate
Autonomic function
test abnormal
Cardiac arrhythmia Tachy- or brady-arrhythmia
Brugada syndrome (genetic disease characterized
by abnormal ECG findings & increased risk of
sudden cardiac death) ECG & holter
Long QT syndrome
Sick sinus syndrome
Complete heart block
Structural cardiac lesions Aortic stenosis Echocardiogram
Hypertrophic obstructive cardiomyopathy (HOCM)
Carotid artery stenosis Haemodynamically significant stenosis may cause
syncope with transient hypotension by sudden Perform carotid
standing, hot bath & large meals doppler or computed
Risk factors: co-existing cardiac disease, post –RT tomography
NPC, fibromuscular dysplasia angiography (CTA)
Subclavian steal syndrome Subclavian artery stenosis proximal to ostium of VA
Psychogenic Panic disorder May be precipitated
Conversion disorder by hyperventilation

Seizures

First seizures
- Diagnosis can be difficult but good clinical skill needed
- Misdiagnosis often “revived by”
 Better history taken from carers and other witness accounts (24%)
 Discussion with neurologists (18%)
 Short-term recurrence of seizures – monitoring of patients may be beneficial (47%)
 Obtaining EEG evidence (44%)

Acute symptomatic seizures

- Clinical seizures from history, examination & evaluation
- Clinical seizures are related to underlying acute medical cause thus provoking seizures
- “Provoking” cause is not the same as “precipitating” factor
- Proximity of time to the provoking cause
Head injury 7 days
CVA 7 days
CNS infection During the course
CNS tumour Presenting symptom
Post-op surgery Immediate post-op period
- Multiple seizures within the same admission
55 Joyce Kwan
 - Short-term clusterin of seizures (during admission)
- Multiple causes possible (uraemic patient with acute encephalitis & first seizure)
- Account for up to 50% of patients with first-ever seizure
- High short-term mortality

Causes
- CNS
 Acute ischaemic/haemorrhagic stroke
 Sagittal sinus thrombosis
 Encephalitis
 Head trauma
» Intracranial, subdural or subarachnoid haemorrhage
 Brain tumour/arteriovenous malformation
 Eversible posterior leukoencephalopathy syndrome
- Metabolic
 Severe hyponatraemia (Na+ < 126mmol/L)
 Hypoglycaemia
 Severe drug intoxication or withdrawal
 Uraemic patients with exposure to toxins (cephalosporin or star fruits)
- Toxic
- Withdrawal
Acute condition Clinical clues
Intracranial haemorrhage, subarachnoid Seizure
haemorrhage & subdural haemorrhage Headache
Presence of persistening neurological signs
CNS infection Seizure
Headache
Altered mental state
Fever
Toxic/withdrawal Seizure
History of overdose or withdrawal of drug
Metabolic Seizure
Electrolyte disturbance
CRF + high dose cephalosporin
CRF + ingestion of starfruit (oxalate)
RPLS Seizure
High BP or concurrent use of
cytotoxics/immunosuppressants

Treatment
- Rectifying underlying cause
- Short-term antiepileptic drugs (AED)
- Careful monitoring

Remote symptomatic seizures

- Underlying enduring cause for repeated seizures can be found as a structural lesion

Causes
- Old CVA
- Glioma
- Mesial temporal sclerosis
 Important for temporal lobe epilepsy

56 Joyce Kwan
Treatment
- Need lifestyle modification
- may consider AED if benefit outweighs side effects

Cryptogenic seizures
- Repeated seizures observed in the absence of any structural lesions
- EEG may or may not be normal

Treatment
- May defer AED treatment
- Needs lifestyle modification

Idiopathic generalised seizures

- Underlying enduring cause for repeated seizures
- Found as suggested by electroencephalographic (EEG) evidence
- Juvenile myoclonic epilepsy (polyspike wave)

Treatment
- Needs lifestyle modification
- Seek specialist advice

Psychogenic seizures
- Functional disorder with clinical presentation akin to seizures

Status epilepticus
- Definition: >2 epileptic seizures without full recovery of consciousness between attacks within 30
minutes and/or continuous convulsive seizures > 2 minutes
- Life-threatening condition in which the brain is in a state of persistent seizure
- ABC most important
- Consider IV lorazepam (ativan) in doses of 1 – 4 mg
 Alternatively, IV diazepam 5 – 10 mg
- Consider IV phenytoin
 Loading dose 10 – 15 mg/kg at 25 – 50 mg/min
 Consider 2 – 3 times longer in elderly & consider cardiac monitoring

Epilepsy
- A tendency toward recurrent seizures unprovoked by systemic or neurological insults
- Operationally defined as >2 unprovoked seizures
- Electrophysiological changes underlying seizure onset, spread & cessation remain unclear
57 Joyce Kwan
 - Types of seizures
 Complex partial seizure
 Partial seizure with secondary generalization (generalised tonic clonic seizure)
 Absence seizure
 Myoclonic seizure
- Recurrence after first unprovoked seizure risk factors
 Strong predictors
» Remote symptomatic cause (e.g. old stroke, tumour, trauma)
» Epileptiform discharge on EEG
 Conflicting/weak predictors
» Partial seizure
» Prior provoked seizures
» Prior febrile seizures
» Seizures while asleep
» Status epilepticus
» Todd’s paresis
» Family history of seizures
 No effect
» Age, sex

Treatment
- Treat if high likelihood of recurrence
 CNS structural abnormality
 Specific syndromes
 Other risk factors
 Social consequence of recurrence
- Wait and see if low likelihood of recurrence
 Infrequent seizures
 Precipitating lifestyle factors
 Anticipated poor compliance
- Commence treatment after 2 seizures, starting with one drug
- Choice depends on
 Classification of seizure
 Side effect profile
 Drug-drug interactions
 Chronic complications (including teratogenicity)

Pharmacological treatment
- Usage of anticonvulsants
- Annual recurrence after 1st seizure (if unprovoked) is ~30%
 May be increased to 50% if additional risk factors
- Approximately 60 – 70% patients are rendered seizure-free with 1st or 2nd anti-epileptic drugs
- When the 1st drug fails due to inefficacy, substitution may be considered
- If 1st drug reduces seizures substantially but only not reaching seizure freedom, immediate add-on
can also be contemplated
Add-on & monotherapy Add-on only
Phenobarbital (Pb) Clobazam
Phenytoin (PHT) Clonazepam
Carbamazepine (CBZ) Vigabatrin
Established Valproate (VPA) Lacosamide (LCS)
Lamotrigine (LTG) Retigabine (RTG)
Gabapentine (GBP) Tiagabine
Oxcarbazepine (OXC) Zonisamide
New Topiramate (TPM)
Pregabalin (PGB)
Levetiracetam (LEV)
58 Joyce Kwan
Seizure type “First line” “Second line”
Carbamazepine Valproate
Lamotrigine
Oxcarbazepine
Partial onset Phenytoin Gabapentin
Topiramate
Levetiracetam
Pregabalin
Valproate Lamotrigine
Primary GTCS Carbamazepine Oxcarbazepine
Phenytoin Topiramate
Absence Valproate Ethosuximide
Lamotrigine
Myoclonic Valproate Levetiracetam
Lamotrigine

Adverse reactions
- Skin rash 5 – 10% in
 Carbamazepine: HLA-B 1502
 Phenytoin
 Lamotrigine
 Oxcarbazepine
- Steven-Johnson Syndrome 0.1 – 6% overall
Add-on & monotherapy Side effects Add-on only Side effects
Phenobarbital (Pb) Cognitive side effect Clobazam Dependence
Phenytoin (PHT) Gum hypertrophy Clonazepam Dependence
Carbamazepine (CBZ) Rash Vigabatrin Visual field defects
Hyponatraemia Lacosamide (LCS) QT prolongation
Valproate (VPA) Weight gain Retigabine (RTG) Bladder dysfunction
Lamotrigine (LTG) Rash Pigmentation
Mild cytopenia Tiagabine -Not available in HK-
Gabapentine (GBP) Cognitive side effects Zonisamide
Oxcarbazepine (OXC) Hyponatraemia
Topiramate (TPM) Renal stone
Glaucoma
Numbness
Pregabalin (PGB) Slight oedema
Levetiracetam (LEV) Behavioural problem

Drug-drug interactions
- Mode of elimination
Renal excretion Liver metabolism Mixed elimination
Gabapentin Benzodiazepines Topiramate
Levetiracetam Carbamazepine
Vigabatrin Ethosuximide
Lamotrigine
Oxcarbazepine
Phenobarbital
Phenytoin
Valproate
- Phenytoin, carbamazepine metabolism inhibited by
 Erythromycin
 Cimetidine

59 Joyce Kwan
  Dextropropoxyphene (doloxene, Dologesic)

Anti-epileptics in pregnancy
- PHT: cleft palate
- CBZ: cleft palate
- VPA: neural tube defects & facial clefts
- Pb: cardiac malformations
- To reduce the risk of major congenital malformations, avoid the use of polytherapy during 1 st
trimester, if possible, compared with monotherapy
- Significant dose relationship with valproate and lamotrigine but not with carbamazepine
 Dose cut-off was 10000 mg daily for VPA
- Limiting the dosage of VPA or LTG during the 1st trimester, if possible, should be considered

Placetal/milk passage
- Probably crosses the placenta
 Phenobarbitone
 Phenytoin
 Carbamazepine
 Valproate
 Levetiracetam
- Possibly crosses the placenta
 Gabapentin
 Lamotrigine
 Oxcarbazepine
 Topiramate
- Degree of penetration in milk (highest  lowest)
 Levetiracetam
 Gabapentin
 Lamotrigine
 Topiramate
 Valproate
 Phenobarbitone
 Phenytoin
 Carbamazepine

Non-pharmacological treatment (if drug resistant)

- Surgical resection
- Vagal nerve stimulator
- Ketogenic diet (children)

Surgical treatment
- Selection of potential surgical candidates
 Phase I
» Structural brain imaging
» Video EEG (VEEG) monitoring
» Clinical psychological testing
 Phase II
» Functional imaging: PET/SPECT
» Intracranial EEG/mapping
» Wada test
 Test to determine which side of the brain is responsible for certain vital
cognitive functions, namely speech and memory

Engel classification system

- Engel classification system is a seizure-outcome scale that is usually used to determine the efficacy of
epilepsy surgery
60 Joyce Kwan
 - Class I
 Free of disabling seizures
» Completely seizure free
» Nondisabling, simple partial seizures only
» Some disabling seizures, but free of disabling seizures for at least 2 years
» Generalised convulsion with antiepileptic drug withdrawal only
- Class II
 Rare disabling seizures
» Initially free of disabling seizures, but rare seizures now
» Rare disabling seizures since surgery
» More than rare disabling seizures but rare seizures for at least 2 years
» Nocturnal seizures only
- Class III
 Worthwhile improvement
» Worthwhile seizure reduction
» Prolonged seizure-free intervals amounting to more than half the follow-up period
but not less than 2 years
- Class IV
 No worthwhile improvement
» Significant seizure reduction
» No appreciable change
» Seizures worse

Hong Kong Epilepsy Guideline

- Referral for tertiary centre
 Drug resistant epilepsy
 Individual aged under 2 years
 Unacceptable side-effects from medication
 Unilateral structural lesion
 Psychological/psychiatric co-morbidiy
 Diagnostic doubt as to nature of seizures
 Testable hypothesis for localizing epileptogenic zone
- Risk of major congenital malformations is increased with use of ‘old’ AEDs
- Daily dose of folate 5mg recommended for pregnant women on AEDs
- Epilepsy diagnosis prohibits all professional drivers from driving
 Not mandatory of physicians to report however physicians should encourage patients to
voluntarily report their illness to Transport Department
 Good practice to document that you have discussed this with the patient in the medical
notes

Epilepsy in children
- Increase in susceptibility compared with adults
 Precocious development of excitatory neurotransmission
 Delayed development of inhibition
 Incomplete myelination
 Late maturation of endogenous systems in seizure control
- Underlying aetiology  age of presentation
 Congenital malformations
 Metabolic conditions (IEM)
 Genetic conditions
- Differs from adult epilepsy by
 Electroclinical syndromes
 Epilepsy mimics
 Disease evolution
 Treatment considerations

Electroclinical syndromes
61 Joyce Kwan
 - Neonatal (<44 gestation weeks)
 Benign familial neonatal seizures
 Early myoclonic encephalopathy
 Ohtahara syndrome (Early Infantile Epileptic Encephalopathy with Burst-Suppression
[EIEE])
- Infancy (<2 years)
 Migrating partial epilepsy of infancy
 West syndrome
 Myoclonic epilepsy in infancy (MEI)
 Benign infantile seizures
 Dravet syndrome
 Myoclonic encephalopathy in nonprogressive disorders
- Childhood
 Febrile seizures plus (FS+)
 Panayiotopoulus syndrome
 Epilepsy with myoclonic atonic seizures
 Bening childhood epilepsy with centrotemporal spikes (BCECTS)
 Autosomal dominant nocturnal frontal lobe epilepsy (ADNLFLE)
 Late onset childhood occipital epilepsy (Gastaut type)
 Epilepsy with myoclonic absences
 Lennox Gastaut Syndrome
 Epilepsy encephalopathy with continuous spike-and-wave during sleep (CSWS)
 Landau Kleffner syndrome (LKS)
 Childhood absence epilepsy
- Adolescence – Adult
 Juvenile absence epilepsy (JAE)
 Juvenile myoclonic epilepsy (JME)
 Epilepsy with generalised tonic-clonic seizures alone
 Progressive myoclonic epilepsies (PME)
 Autosomal dominant partial epilepsy with auditory features (ADPEAF)
 Other familial temporal epilepsies

Natural evolution
- Epileptic encephalopathy
 Certain forms of epileptic activities lead to severe cognitive & behavioral impairment
 By suppressing or preventing the epileptic activity may improve the cognitive & behavioural
outlook of the disorder
 Most common & most severe in developing brain
 E.g. West syndrome, Lennox Gastat
- Benign
 Self-limited
 Spontaneous remission
 Defined age of onset

Differential diagnoses
- Jitteriness
- Sleep myoclonus
- Breath-holding
- Syncope
- Hyperventilation
- Gastroesophageal reflux
- Tics
- Dystonia
- Sleep-related disorders
- “Non-epileptic seizures”

62 Joyce Kwan
Physical examination
- Head circumference
- Neurocutaneous stigmata
- Development
- Focal neurological sign

Comorbidities
- ADHD
- Autistic spectrum disorders
- Disrupted sleep
- Failure to thrive
- Drooling of saliva
- Migraine
- Behavioural/mood problems

Treatment
- Ketogenic diet
- Steroid
 Common used in “epileptic encephalopathy”
 E.g. West syndrome, Landau Kleffner Syndrome
 Concern on epileptiform discharges & neurodevelopment
- Epilepsy surgery
 If suitable candidate (epileptogenic zone identified) and technically feasible, the earlier the
better

Childhood absence seizures

- Prognosis: good
- Later the onset of typical absence seizures, the higher is the risk of convulsive seizures
 GTCs developed in 16% of patients with onset of typical absence seizures before 9 years of
age
 Up to 44% for those with onset between 9 – 10 years

Infantile spasm (IS)

- Spasm: symmetrical, bilateral, brief & sudden contractions of
the axial muscle groups
- “Salaam attacks”
 Body bend at the waist & adduction of the upper
extremities
 Soon after awakening or on falling asleep
- In clusters
Infantile spasm
- Treatment
 Refractory
» Prednisolone/ACTH
» Vigabatrin
» Convetional AEDs
» New AEDs
» Ketogenic diet
- Prognosis
 Only ~5 – 12% of patients have normal mental & motor development
» Better if cryptogenic
 ~½ left with motor impairment
 70% to 78% are mentally retarded
 When the spasms stop, many children later develop other kinds of epilepsy

63 Joyce Kwan
Dravet syndrome/SCN1A-related seizure disorders
- A spectrum (common pehnotypes)
 Febrile seizures
 Generalised epilepsy with febrile seizure plus dravet
syndrome (severe myoclonic epilepsy in infancy)
 Intractable childhood epilepsy with GTC (ICE-GTC)
 Infantile partial seizures with variable foci
- Progressive epileptic encephalopathy
- Mostly genetically based
 SCN1A sodium channels has increased sensitivity and
exhibit hyperexcitability
- Seizures
 Early onset of infantile febrile clonic convulsions
 Myoclonic jerks
 Atypical absences
 Complex focal seizures
- Polymorphic seizures
- Resistance to treat ment
- Progressive deterioration
 Mild
» Febrile convulsions
» Status epilepticus
 Aggressive
» Intractable polymorphic seizures
 Static
» Improving seizures but severe deficit
- Diagnosis for
 Prognosis implication
 Investigation strategy
 Therapeutic implication
 Genetic counseling

Therapeutic implication
- Drugs: affect GABA receptors
 Benzodiazepines
 Stiripentol
 Topiramate (TPM)
 Epilim
 Phenobarbitone (PHB)
- Drugs to be avoided
 Carbamazepine
 Lamotrigine
 Vigabatrin
 Phenytoin

Febrile seizures
- Common: 2 – 5%
- Age: 3 months – 5 years
- Tonic-clonic seizures when they have a high fever
- Slight tendency to run in families
- Treatment
 Control the seizures
» Recovery position
» Rectal diazepam
» Midazolam
 Control the temperature

64 Joyce Kwan
 - Prognosis
 Excellent
 First febrile seizure before one, ½ will have at least one more
 First febrile seizure after one, ¼ will have more
 3 – 6% with epilepsy in later life
» especially generalised epilepsies

Benign childhood epilepsy with centrotemporal spikes

(BCECTS)
- Peak: 7 – 8 years old
- Nocturnal generalised seizures of probable focal
onset
- Diurnal partial seizures arising from the lower
rolandic area
- >50%: seizures during sleeping alone
- 15%: during sleep & while awake
- 10 – 20%: in the waking state alone
- Seizures
 Somatosensory stimulation of the oro-buccal cavity (may not complain)
 Speech arrest
 Preservation of consciousness
 Excessive pooling of sliva
 Tonic or tonic-clonic activity of the face
 May spread to arms/legs
- EEG shows midtemporal-central spike focus
- Prognosis
 Remission within 2 – 4 years from onset & before 16 years
 <10% have frequent seizures
 May have linguistic abnormalities
 <2% with generalised epilepsy in adults

B6 related seizures
- Spectrum of “rare” disorders
- Early/refractory epilepsy
- Lumbar puncture for neurotransmitters may aid the diagnosis
- Pyridoxine/pyridoxal phosphate responsive
- Ketogenic diet may help in treatment

65 Joyce Kwan
Diseases of the spinal cord & roots
- Ascending tracts
 Dorsal column
» Proprioception (movement & joint position)
» Discriminative (fine) touch
» Vibration
 Spinothalamic tract
» Pain
» Thermal sensations
» Non-discriminative (coarse) touch
» Pressure
- Spinal shock (caused by trauma) leads to
 Sudden loss of spinal cord function including reflex
however it is transient
 Can recover spontaneously
 To confirm, test bulbocavernosus reflex
 Most key muscle have MRC grading < 3
- Complete cord injury causes permanent damage

Assessment
- Loss of function
 Motor
 Sensory
 Reflexes
 Autonomic
- Pain
 Mechanical
 Inflammatory
 Neuropathic pain

Mechanical pain
- Associated with spinal instability
 Inability of the spine to prevent initial or additional damage to the neural elements,
deformity or pain from structural changes
- Elicited by movement
- Improve with rest
- Somatic sensation
- From joints or fractures
- Local pain and/or referred pain (e.g. sciatica)

Inflammatory pain
- Arthritis and reaction to injury
- Local & referred pain
- Lasts for days
- Relief with anti-inflammatory drugs  local injection of steroid or local anaesthesia

Neuropathic pain
- Inappropriate response caused by a lesion or dysfunction in the peripheral or central nervous
system e.g. injury/compression
- Character
 Burning
 Shooting
 Lancinating
 Electric shock-like pain
 Dysaesthesias
 Hyperalgesia
66 Joyce Kwan
  Allodynia
- Mechanisms
 Central/peripheral sensitization
 Loss of central inhibition
 Reorganization of central A fibres
 Ectopic discharge
- Tests
 Spurling’s test
 Shoulder abduction test
 Supine straight-leg raise test
 Seated straight-leg raise test
 Femoral stretch test

Spinal injury
- Location of injury
 Cervical (40%)
 Thoracic (10%)
 Thoracolumbar (35%)
 Lumbar (3%)
 Others (14%)
- Mechanism of injury
 Hyperextension
 Flexion
 Axial compression
 Horizontal translation
 Rotation
 A combination of the above
- Variable clinical features (one or combination)
 Neurological deficit from spinal cord or nerve damage
 Severe pain at the spine
 Self limitation of movement
 Muscle spasm
 Symptom of spinal instability
- Vertebral column stability
 Depends on the ligaments, facet joint & vertebral body
 Abnormal angles varies with the level of the spine
 Associated vertebral injuries
» Displacement of bone fragments
» Articular process dislocation or fracture
» Disc herniation

Investigations
- To determine the stability of vertebral columns
- To determine any cord compression
- Reversible compression
 Extradural haematoma
 Bone fragment
 Herniated disc
- Plain X-ray often used as initial/only examination
- Computed tomography useful when there is a localizing neurological symptom or sign
- Magnetic resonance imaging for cases with neurological deficit

Cervical spine
- Important measurements in the cervical spine
 Predental space
» < 3 mm
» < 5 mm
67 Joyce Kwan
  Depth of spinal canal
» > 13 mm
 Depth of prevertebral soft tissue
» Above larynx < 7 mm
» Below larynx < 22mm or depth of body
 Overriding of vertebral bodies
» Without fracture
 25% indicates unifacetal dislocation
 50% indicates bifacetal dislocation
» With fracture
 < 3.5 mm indicates instability

C1 rotatory subluxation
- RTA victim or children
- Signs
 Neck pain
 Spasm
 Torticollis deformity
- Investigation
 X-Ray: Open-mouth odontoid view
» Asymmetric distance from the two lateral mass
- Treatment
 Traction Odonotoid fracture
 Cast immobilisation
 Surgery for delayed cases

Odontoid fracture
- High velocity or fall
- 2 types
- Treatment
 Halo immobilisation
 Surgery

Hangman’s fracture
- Fractured pedicles of C2
- Extension & compression or distraction Hangman’s fracture
- Treatment:
 Collar immobilisation for 3 months

Lower cervical spine (C3 – C7)

- Posterior column
 Spinous process avulsion
 Facet fracture & dislocation
- Anterior column
 Compression fracture
 Burst fracture
 Tear drop fracture

Spinal cord injury

- Complete cord syndrome
 No motor or sensory function
 Loss of reflexes at the level of lesion
 Hyperreflexia at level below lesion
- Incomplete cord syndrome
 Anterior spinal cord lesion
 Central spinal cord lesion
68 Joyce Kwan
 » Syringomyelia
» Trauma/contusion especially with concomitant stenosis
» Minor
 Affects anterior horn cells
 Paresthesia felt by the patient
 Anterior column affected
» Major
 Starts to affect corticospinal tract
 Posterior spinal cord lesion
 Brown-Sequard (hemi-cord) syndrome
- Conus medullaris syndrome (UMN affecting cord)
 Bilateral symmetrical sensory loss
 Lower level affected first (saddle distribution)
 Sphincter involve early
 Motor weakness not prominent
- Cauda equina syndrome (LMN affect nerve root)
 Radicular pain
 Motor (LMN) deficit is common
 Sensory deficit is asymmetrical
 Sphincter involvement is late
- Haematomyelia
- Cord oedema
- Axonal injury
- Epidural haematoma
- Subdural haematoma
- Root avulsion
- Isolated root(s) symptom
- Other patterns of deficits

Acute management
- Immobilisation
 Spinal broad & rigid neck collar
 Immobilisation u ntil spine fracture excluded
- Resuscitation
 ABC
 Fluid
- Document neurological deficit
- Investigations
 X-ray
 CT scan
 MRI
- May give decompression, fixation or fusion

Prolonged immobilisation Internal fixation

- Cervical fracture
 Halo jacket brace to facilitate rehabilitation
 Consider internal fixation
- Thoracolumbar spine fracture
 Bed rest
 External brace
 Consider internal fixation
- Fixation
 Process of stopping movement between Halo jacket
pieces of bone using implants (screw, plate,
rod or wire)
» All metal will break with time
- Fusion
69 Joyce Kwan
  Induction of healing process between bone fragments
so that pieces of bone become permanently “fixed”
 Bone graft usually used

Long term problems

- Mobilisation C1-C2 fusion
- Urinary problems
- Muscle spasticity
- Respiration problems
- Cardiovascular problems
- Gastrointestinal problems
- Skin care (bed sores)
- Psychosocial care
- Financial problems

Spinal degeneration
- Dysfunction phase
 Nuclear degeneration
 Annular tears
 Facet arthritis
 Acute disc herniation
- Instability phase
 Reduction in disc height
 Laxity of ligaments & facet capsules
 Degeneration of facet joints
 Increase in motion
- Restabilisation phase
 Osteophyte formation
 Facet hypertrophy
 Desiccation of the disc
 Increase in intradiscal collagent

Symptoms
- Spinal cord compression
 Osteophytes
 Spinal stenosis
 Ossified posterior longitudinal ligament (OPLL)
- Spinal nerve compression
 Prolapsed intervertebral disc
 Facet joint hypertrophy
- Pain
 Facet arthritis
 Instability
 Neuropathic pain (including sciatica, radiculopathy)
 Local referred pain
» Usually around the back & neck
» Seldom extend beyond knee/elbow
» Somatic pain (sharp pain character & control with analgesics)
 Neuropathic pain
» Include sciatica & radiculopathy
» Extend according to distribution of a nerve (e.g. L5 region)
» Neuropathic in character
 Burning & shooting
» Difficult to control with NSAID or analgesic

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Prolapsed disc disease
- Spectrum of disc degeneration
- Desiccation or disc protrusion
- Plain X-ray
 Loss of intervertebral disc height
 End plate osteophytes & vacuum disc
- Annular tear
- Bulge
- Protrusion
- Extrusion
- Sequestration

Treatment of spinal degeneration

- Rest
- Physiotherapy
- Anti-inflammatory drugs
- Drugs for neuropathic pain
- Epidural or corticosteroid
- Decompression of spinal cord or nerve
 Discectomy
 Laminectomy
 Corpectomy
 Formaminotomy
 Medial facetomy
 Laminoplasty
- Fixation of instability

Spinal stenosis
- Lumbar spinal stenosis
 Pain
 Weakness
 Numbness in the legs, calves or buttocks
 Symptoms increase when walking short distances
 Symptoms decrease when sitting, bending forward or lying down
- Cervical spinal stenosis
 Pain
 Weakness
 Numbness in the shoulders, arms or legs
 Hand clumsiness
 Gait & balance distrubances

Investigations
- X-ray Spine
 AP
 Lateral
 Flexion-extension
- MRI scan
- Plain CT scan
- Myelogram & CT myelogram
- Nerve conduction study

Spinal tumours
- Symptoms
 Neck, back or suboccipital pain
 Limb weakness  muscle atrophy
 Numbness and decrease in sensation
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  Limb stiffness, fatigability & spasticity
 Scoliosis/kyphosis
 Sciatica
 Hydrocephalus
» Headache & vomiting
 Bladder dysfunction in the later state

Spinal tumour in adults

- Extramedullary: 2/3
 Nerve sheath tumour (40%)
 Meningioma (40%)
 Filum ependymoma (15%)
 Miscellaneous (5%)
- Intramedullary: 1/3
 Ependymoma (45%)
 Astrocytoma (40%)
 Hemangioblastoma (5%)
 Miscellaneous (10%)

Spinal tumours in children

- Intramedullary (36%)
 Astrocytoma (23%)
 Ganglioglioma (4%)
- Intradural extramedullary (27%)
 Ependymoma (7%)
 Dermoid/epidermoid (6%)
 Schwannoma (4%)
 Lipoma (4%)
- Extradural (24%)
 Neuroblastoma (8%)
 Sarcoma (7%)
 Primary neuroectodermal tumour (4%)

Treatment
- Most are benign tumours
- Primary treatment is surgical excision
- Minimal damage to normal nerves
- Biological aggressive tumour may require adjuvant radiotherapy

Treatment of intramedullary tumour

- Surgical excision achievable in many cases with benign tumour
- Role of excision of malignant tumour is limited
- Need midline myelotomy
- Intraoperative electrophysiological monitoring
- Post-operative radiotherapy for selected cases with malignant or recurrent tumour

Prognosis
- Most spinal tumour are benign
- Prognosis depends on
 Preoperative neurological function
 Location of the lesion
 Surgical technique
- Prognosis for malignant tumour depends on the susceptibility to adjuvant therapy

Arteriovenous malformation
- Location: thoracolumbar region most commonly affected
72 Joyce Kwan
 - Clinical features vary
 Haemorrhage in about 50% of cases
- MRI might show enlarged vessels  haematoma
 Cord can be atrophic
- Spinal angiography for diagnosis

Infection of spine
- Spondylitis
- Discitis
- Epidural abscess
- Cord abscess
- Pattern of involvement
 Children
» Disc space first then vertebrae
 Adults
AVM
» Subchondral vertebral body then disc space

73 Joyce Kwan
 CT

Radiology of the spine

- Plain X-ray CT – Fibrous
 Alignment dysplasia
 Bone defects
 Disc spaces
 Soft tissues
- Computed Tomography (CT)
 Alignment X-ray
 Bone defects
 Disc spaces
MRI
 Soft tissues
 Cross-sectional imaging for bone details
 3-dimensional reconstruction
- Magnetic Resonance Imaging (MRI)
 Commonly used in detection of
» Disc disease
» Infection
» Intraspinal tumour
» Bone metastasis
- Nuclear medicine
 Used in persistent back pain without an
apparent underlying cause
 May be able to detect early metastases
before it is detectable on CT

Investigations of spinal injury

- To determine the stability of vertebral columns MRI
- To determine any cord compression
- Reversible compression
 Extradural hae matoma
 Bone fragment
 Herniated disc

Trauma/fracture
X-ray: C2/3 dislocation
- Plain X-ray & CT assessment of bone
fracture/alignment
- MRI for assessment of associated soft tissue injury
MRI spine: bilateral disc Disc
defect protrusion

CT: burst fracture

MRI spine: cord
contusion

Prolapsed disc disease

- Plain X-ray
 Loss of intervertebral disc height
74 Joyce Kwan
  End plates osteophytes
 Vacuum disc

Investigation of spinal tumours

- Guided by neurological examination
- X-ray of spine
- MRI spine
 Sensitive, but sometimes have artifacts
 Location & characteristic of lesion
- Spinal angiography CT spine: burst fracture
- Aim of investigations
 Determine the level of lesion
 Intramedullary or extramedullary
 Cord compression or not
 Single or multiple lesion
 Any syringomyelia (cyst or cavity within
the spinal cord) Long cervical
 Shape & pattern of enhancement may help schwannoma Bone
Metastases
in differentiation

Extradural tumour
- Erosion of bone
- Loss of normal bone marrow signals
- May have associated pathological fracture
- Compression of spinal cord or nerve roots

Metastasis
- Assessment of extent of bone involvement
 Bone scan
- Assessment of cord/nerve root compression
 Computed Tomography Metrizamide Myelography (CTMM)
 MRI

Nerve Sheath Tumour

- Most common intradural extramedullary tumour
- Usually in middle age adults
- Location variable
- 100% enhancement

Extramedullary tumour
- Iso- or hypo-intense on T1 weighted MRI Meningioma
- Typically enhanced on T1 weighted MRI after Gadolinium contrast injection

- Spinal cord appears thin-out & compressed

- There may be dumbbell extension to extraspinal space

Meningioma
- Usually benign
- Second most common cause of spinal tumour
- Most common site: thoracic spine
- Female > male
- 90% intradural extramedullary

Intramedullary tumour
- Isointense on T1 weighted MRI

75 Joyce Kwan
 - Spinal cord appears thickened
- Hyperintense on T2 weighted MRI
- Much enhancement on T1 weighted MRI after Gadolinium contrast injection
- May be associated with syringomyelia

Spinal astrocytoma
- Hyperintense due to Gadolinium contrast & enlargement of spinal cord
- Erosion of vertebral body
Astrocytoma
Arteriovenous malformation (AVM)
- Location: thoracolumbar region is most commonly Spinal AVM
affected
- Clinical features vary
 Haemorrhage in around 50% of cases
- MRi might show enlarged vessels  haematoma
 Cord can be atrophic
- Spinal angiography is diagnostic
 Gold standard but invasive

Spinal haematoma
- Related to
 Trauma Spinal angiography of AVM
 Vascular malformation
 Bleeding tendency
 Idiopathic
- Clinical features are acute onset
- MRI signal varies according to the onset time
Blood Products T1 Signal T2 Signal
Hyperacute Oxyhaemoglobin/Serum Intermediate Bright
Acute Deoxyhaemoglobin Intermediate Dark
Subacute, Early Intracellular Bright Dark
methemoglobin
Subacute, Late Extracellular Bright Bright
methemoglobin
Chronic Haemosiderin Dark Dark

Myelomeningocele
- Spinal dysraphism with incomplete midline closure elevated maternal serum alpha-fetoprotein
- Lumbar region most commonly affected

Infection of spine
- Spondylitis
- Discitis
- Epidural abscess
- Cord abscess
- Pattern of involvement
 Children: disc space first then vertebrae
 Adults: subchrondral vertebral body  disc space
- Plain X-ray TB spine
 Usually normal for the first 2 weeks after onset of
symptoms
- End plate erosion & disc space narrowing
 Late detection
- MRI
 Narrowed disc space & low signal in adjacent bodies
 Subligamentous or epidural soft tissue masses
76 Joyce Kwan
  Cortical bone erosion

TB spondylitis
- Lower thoracic & lumbar spine most commonly affected
- > 2 vertebral bodies affected
- Skip lesions are common
- Can be associated with paraspinous abscesses

77 Joyce Kwan
Movement Disorders

Parkinsonism
- Bradykinesia +
 Rigidity
 Resting tremor
 Postural instability

Parkinson’s disease
- Bradykinesia
- Rigidity
- Tremor
 75% of PD patients
 Rest tremor, 4- 6 Hz
 Can be action tremor – raise arm, initially no tremor then tremor will reappear
 Starts at hand more commonly than foot
- Postural instability
 Later feature
- Insidious onset
- Asymmetrical presentation
- Rigidity: lead-pipe or cogwheel
- Postural instability
- Non-motor symptoms (may manifest before motor symptoms)
 Hyposmia or anosmia (90%)
 Depression
 Constipation (major symptom)
 REM sleep-behavioural disorders (RBD)
» Usually flaccid paralysis, paradoxically tighten limb tone & have nightmares (fighting
scenes)
 Oily face
 Bradyphrenia (slow thinking)
 Dementia of frontal lobe type (difficulty in multitasking
 Autonomic dysfunction (late)
» Postural hypotension
» Typically after 7 years

Epidemiology
- Incidence: 20 per 100,000 per year
- Prevalence: 200 – 300 per 100,000
- Age
 Both incidence & prevalence increase with age
 Mean age of onset 55 – 60 years old
 Increase steadily up to 9th (incidence) & 10th (prevalence) and then
decline

Pathology
- Presence of Lewy bodies
 Ventral strip develops degeneration first
 Difficulty in removing toxic metabolites & thus neurons attempt to
contain all of them in lewy bodies
- 5 – 25 m
- Core, body & halo
- Brainstem type & cortical type
- Contains
 Protein
 Free fatty acids
78 Joyce Kwan
  Sphingomyelin
 Polysaccharides

Medical treatment
- MAO-B inhibitors Usage of Levodopa
- Anticholinergics
- N-methyl-D-aspartate
inhibitors
- Dopamine agonists
- Levodopa
- COMT-inhibitors
- Adenosine2a
antagonists
- Co-enzyme Q10

Surgical treatment
- Lesional surgery –
stereotatic
thermocoagulation
 Pallidotomy
 Thalamotomy
 Subthalamotomy
- Deep brain stimulation
 Subthalamic nucleus – stops tremor only
 Globus pallidus interna – stops tremor, bradykinesia & rigidity
 VIM thalamus
- Transplantation
 Fetal mesencephalic cells
 Stem cells

Post-op care
- Early post-op
 Resume medication
 Can start DBS in a few days
» “Micro-lesioning”
» Change in tissue impedance
» Adjustment in settings 6 – 8 weeks

Complications
- Surgical complications
 Haemorrhage
 Malposition
- Hardware complications
- Stimulation complications

Parkinsonism-plus syndromes
- Multiple system atrophy (MSA)
- Progressive supranuclear palsy (PSP)
- Cortico-basal degeneration
- Dementia with Lewy Bodies
- Vascular Parkinsonism
- Drug-induced Parkinsonism
- Toxin-induced Parkinsonism

Multiple system atrophy (MSA)

- MSA-P: Autonomic dysfunction + Parkinsonism
79 Joyce Kwan
  Early symptoms
 Male: loss of morning erection
 Female: bladder dysfunction (incontinence)
 Orthrostatic hypotension
 Raynaud’s syndrome
- MSA-C: autonomic dysfunction + cerebellar syndrome

Epidemiology
- Sporadic, progressive
- Incidence 3 – 4 per 100,000
- Prevalence 4.4 per 100,000
- Mean age of onset 55 – 58 years old
- Mean disease duration 7 – 9 years

Clinical features
- Orofacial dystonia
- Disproportionate antecollis
- Camptocormia (severe anterior flexion of the spine) with/without Pisa syndrome (severe lateral
flexion of spine)
- Contractures of hands/feet
- Inspiratory signs
- Severe dysphonia
- Severe dysarthria (soft & low voice
- New/increased snoring
- Cold hands & feet
- Pathological laughing or crying
- Jerky, myoclonic postural or action tremor

Pathology
- Glial cytoplasmic inclusions in oligodendrocytes

MRI changes
- Hot cross bun sign
- Putamen slit sign
Hot-cross bun sign
Management
Putamen slit sign
- Parkinsonism:
 Levodopa (unsustained response)
- Bladdery urgency, incontinence
 Oxybutynin
- Orthostatic hypotension
 Increased salt intake
 Elastic stocking (improve venous return)
 Reverse Trendelenberg position
 Cross leg technique
 Fludrocortisone
 Ephedrine
 Octreotide

Progressive supranuclear palsy (PSP)

- Onset: 60 – 66 years
- Prevalence: 6.4 per 100,000
- Typically presents with axial parkinsonism (hyperextended neck) & tendency to fall backwards

80 Joyce Kwan
Clinical features
- Axial features
 Tendency to fall backwards
 Early loss of postural reflex
 Axial rigidity
- Bradykinesia
- Reptilian stare
 Frontalis overactivity
 Retrocollis
 Markedly reduced blink frequency
» Physiological:
14/min
» PSP: <1/min
- Impaired downgaze
 Later upward & lateral
gazes are affected Neurofibrillary tangles
 Brainstem intact
- Swallowing difficulty Humming bird sign

Pathology
- Neurofibrillary tangles Box-like 4th ventricle
 Hyperphosphorylated tau & Tufted astrocytes
neuropil treads
Oligodendroglial coiled bodies
- Tufted astrocytes
- Oligodendroglial coiled bodies

MRI changes
- Dorsal midbrain atrophy
 Humming bird sign
 Box-like 4th ventricle

Management
- Levodopa (partial & initial response only)
- Botulinum toxin for retrocollis

Cortico-basal degeneration (CBGD)

- Onsent: ~63 years
- Highly asymmetrical progressive akinetic-rigid syndrome
 All concentrate on 1 arm

Clinical manifestations
- Basal ganglia signs
 Akinesia
 Rigidity
 Limb dystonia
 Athetosis
» Semi-purposeful alien movements
» Hyperextension & overpassing pronation
 Alien limb phenomenon
 Dementia (frontal lobe)
 Apraxia
» Cannot carry out normal movements
 Frontal release reflexes
 Dysphasia
- Other manifestations
81 Joyce Kwan
  Postural-action tremor
 Hyperreflexia
 Impaired ocular motility – slow eye movement
 Dysarthria
 Focal reflex myoclonus
 Dysphagia

Neuroimaging
- Asymmetrical fronto-parietal atrophy
- Late representation

Pathology
- Astrocytic plaques
- Neuropil threads

Management
- Parkinsonian features
Astrocytic plaques Neuropil threads
 Levodopa (partial & unsustained response)
- Myoclonus & action tremor
 Clonazepam
- Rigidity & tremor
 Baclofen
- Painful dystonia
 Botulinum toxin

Dementia with Lewy Bodies

- Triad of clinical features
 Atypical parkinsonism
» Postural hand tremor with micro-myoclonus
 Fluctuating cognitive impairment
 Vivid visual hallucination
» Animals & childrens

Pathology
- Cortical & brainstem Lewy Bodies

Management
- Cholinesterase inhibitor
 Rivastigmine
 Donepezil
- Dopaminergic drugs
 May worsen psychosis
 Cannot tolerate high dose  worsen hallucinations
- Neuroleptic
 Will worsen parkinsonism

Vascular Parkinsonism
- Essentially symmetrical parkinsonism features of lower limbs & gait
- Gait
 Initiation hesitation
 Shuffling & terminal hesitation
 Lower limb parkinsonism
- Normal hand function (swinging of arms present)
- Dementia
- Urine incontinence (frontal lobe involvement)
82 Joyce Kwan
 - No tremor

Neuroimaging
- Vascular ischaemic changes
- No hydrocephalus

Management
- Levodopa (partial improvement)
- Physiotherapy
 Gait training
 Fall prevention

Drug-induced Parkinsonism
- Aetiologies
 Dopamine receptor antagonists (classical neuroleptics)
 Anti-dopaminergic anti-emetics
 Presynaptic dopamine depletors
» Reserpine
» Tetrabenazine
 Selective serotonint reuptake inhibitors
 Lithium
 Valproate
 Calcium channel blockers
» Nifedipine
- Subacute after weeks or months of taking medication
- Symmetrical parkinsonism with postural hand tremor
- Less commonly rest tremor
- Usually resolved after stopping the medication for 6 months

Management
- Tail off medication
- Anticholinergics
- If persistent/presence of obvious asymmetry, may be due to underlying
Parkinson’s disease

Toxin-induced Parkinsonism
- Carbon monoxide induced parkinsonism
 Happen 3 weeks after acute CO poisoning
 Symmetrical bradykinesia & rigidity
 Akinetic mutism
 Gait
» Start hesitation
» Short-stepped gait
» Freezing
 Absence of tremor
 Neuroimaging: carbon monoxide poisoning
- Manganism
 Welders, battery workers, miners, chronic accidental
ingestion of potassium permanganate, incorrect
concentration of manganese in parenteral nutrition
 Symmetrical parkinsonism
» Bradykinesia
» Rigidity
 Dystonia
 Cock gait
» Straight back
83 Joyce Kwan
 » Flexed elbow
» Walking on toes
 Manganese madness
 No tremor

Summary
- Multiple System Atrophy (MSA): autonomic dysfunction + parkinsonism/cerebellar syndrome
- Progressive Supranuclear Palsy (PSP): down-gaze palsy + axial parkinsonism
- Cortico-basal Degeneration (CBDG): alien limb + basal ganglia + pyramidal signs
- Dementia with Lewy Bodies: triad of atypical parkinsonism + cognitive fluctuations + visual
hallucinations
- Vascular parkinsonism: lower body parkinsonism
- Drug-induced parkinsonism: symmetrical parkinsonism + preceding relevant drug history
- Carbon monoxide induced parkinsonism: symmetrical parkinsonism with preceding CO
poisoning
- Manganism: parkinsonism + dystonia + cock gait + psychosis

84 Joyce Kwan
Disorders of balance & hearing
- Total >10% of population or over half a million
- Over 1/3 of adults >50 have significant hearing loss
 90% of those who have hearing loss are >50

Symptoms
- Outer ear/middle ear
 Pain
 Discharge
 Deafness
 Blocking
 Tinnitus
- Inner ear:
 Deafness
 Tinnitus
 Communication problems
- Balance symptoms

Examination
- Otoscopy
- Clinical examination of the hearing
system (tuning fork)
- Hearing tests
 Pure tone audiogram
 Speech audiogram
- Vestibular assessment
- Functional evaluation

Conductive hearing loss

- External ear
- Ear canal
- Tympanic membrane (perforations, chronic suppurative otitis media)
- Middle ear (middle ear effusions)
- Ossicular chain
 Due to middle ear infection/trauma
 Congenital
 Otosclerosis

Otitis media
- Otitis media with effusion
 Mucous & serous discharge in middle ear
- Acute suppurative otitis media
- Chronic suppurative otitis media
 Safe
 Unsafe
- Complications of otitis media

Sensorineural hearing loss

- Bilateral hearing loss
 Age-related hearing loss
 Industrial noise-induced hearing loss
 Ototoxic hearing loss
 Asymmetrical bilateral hearing loss
» Weapon firing
» Head injury

85 Joyce Kwan
 » Meniere’s disease
» Bilateral acoustic neuromas
- Unilateral hearing loss
 Trauma & other insults
 Infection
» Pre-natal
» Peri-natal
» Post-natal
 Acoustic neuroma

86 Joyce Kwan
87 Joyce Kwan