Neurology essay – Amyotrophic lateral sclerosis (ALS)

Written by Ariel Sherman

• Diagnosis
• Description of basic characteristics – definition, basic clinical prognosis,
clinical picture, diagnosis and treatment)
• Case report

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, is a

progressive and fatal neurodegenerative disease. It primarily affects nerve cells in
the brain and spinal cord that control voluntary muscle movement. This leads to
muscle weakness, atrophy, and eventually paralysis. ALS affects both upper and
lower motor neurons, resulting in a range of symptoms depending on the specific
neurons involved. There is currently no cure, and treatment focuses on managing
symptoms and slowing disease progression. The disease's cause is largely
unknown, although genetics play a role in some cases. (Grad, 2017)

Clinical prognosis
Early Stage:

Asymmetric muscle atrophy: This typically begins distally, often in the intrinsic
muscles of the hands, making fine motor tasks difficult. Atrophy may also be present
in other muscle groups early on, but is not always widespread initially.

Muscle weakness: Weakness corresponds to the muscle atrophy and can be mild at
first, progressing to more profound weakness over time.

Fasciculations: These are visible, involuntary twitching of muscle fibers. Their

presence, combined with weakness and atrophy, is a strong indicator of ALS. It is
noted that fasciculations can be seen in other neurologic diseases.

Muscle cramps and pain: These are common in ALS.

Later Stage:

Progressive muscle atrophy: The atrophy spreads proximally, affecting larger

muscle groups in the arms, legs, and trunk. This ultimately involves the muscles of
respiration, causing breathing difficulties.

Increased muscle weakness: Weakness becomes more widespread and severe,

leading to significant disability and dependence on others for activities of daily living.

Spasticity: While not always present or prominent early on, spasticity (increased
muscle tone and resistance to passive movement) gradually develops in many
patients, but can remain mild, even in late stages. This contrasts with the early-stage
flaccid weakness.

Hyperreflexia: The intrinsic muscle reflexes (deep tendon reflexes) become

unusually brisk, often more so than would be expected given the degree of muscle
atrophy. This is a key indicator of upper motor neuron involvement, a hallmark of
ALS.

Pyramidal tract signs: These include the presence of Babinski signs (dorsiflexion of
the big toe on plantar stimulation), which confirm upper motor neuron damage.

Bulbar involvement (in approximately 20% of cases): This affects the cranial nerves
that control speech and swallowing, resulting in dysarthria (slurred speech),
dysphagia (difficulty swallowing), and atrophy and fasciculations of the tongue.

Respiratory failure: Due to the progressive weakening of respiratory muscles,

respiratory failure is a common cause of death in ALS. Sometimes, this stage can
progress to a locked-in state.

Other less consistently present, but possible findings:

Distal sensory deficit: In the advanced stage of the disease, a distal sensory deficit
is possible.

Cognitive impairment: frontal dementia is a frequent complication of ALS.

(Mattle & Mumenthaler, 2017)

Clinical picture

I. Disorders Affecting Specific Neurological Systems:

Motor System: Upper motor neuron lesions (affecting the corticospinal and
corticobulbar tracts) cause spastic weakness (increased tone, decreased strength,
impaired fine motor control), hyperreflexia, and pathologic reflexes (Babinski, etc.).
Lower motor neuron lesions (affecting anterior horn cells, nerve roots, peripheral
nerves) cause flaccid weakness (decreased tone and strength), hyporeflexia or
areflexia, muscle atrophy, and fasciculations. Different patterns of weakness (e.g.,
hemiparesis, paraplegia, quadriplegia) help localize the lesion. Cerebellar disorders
manifest as ataxia (incoordination), dysmetria (poor movement control), intention
tremor, and hypotonia.

Sensory System: Sensory disturbances are categorized by location (peripheral vs.

central) and modality (touch, pain, temperature, proprioception, vibration).
Peripheral lesions cause deficits in the distribution of the affected nerve(s) or nerve
root(s), while central lesions (spinal cord, brainstem, thalamus, cortex) cause deficits
with specific patterns (e.g., dissociated sensory loss).

Autonomic Nervous System: disturbances in sweating, bladder/bowel/sexual

function, blood pressure regulation, and the appearance of Horner's syndrome
(ptosis, miosis, anhidrosis). These can be isolated or part of broader neurological
conditions.
II. Specific Neurological Diseases (examples):
 Multiple Sclerosis (MS): Clinical pictures vary depending on the course (relapsing-
remitting, secondary progressive, primary progressive). Common manifestations
include optic neuritis (visual disturbances), oculomotor palsies (diplopia), sensory
disturbances (paresthesia, numbness), pyramidal tract signs (spasticity,
hyperreflexia), cerebellar signs (ataxia), bladder dysfunction, fatigue, and
depression. importance of MRI to demonstrate the characteristic scattered lesions.

Amyotrophic Lateral Sclerosis (ALS): This is characterized by combined upper and

lower motor neuron damage, resulting in progressive weakness, atrophy,
fasciculations, hyperreflexia, and pyramidal tract signs. Bulbar involvement
(affecting speech and swallowing) is common.

Parkinson's Disease: The clinical triad of hypokinesia (slow movement), rigidity, and
tremor (at rest) is described, along with postural instability, impaired olfaction, and
various nonmotor features (autonomic dysfunction, cognitive and psychiatric
problems).

Epilepsy: Generalized seizures (tonic-clonic, absence) and focal seizures (with and
without altered consciousness) are categorized by their clinical manifestations,
including motor, sensory, and autonomic features. Status epilepticus is highlighted as
a life-threatening condition.

III. Pain Syndromes:

Headache: primary headaches (migraine, tension-type, cluster) and secondary

headaches (related to intracranial hemorrhage, tumors, infections, etc.), emphasizing
the importance of recognizing "red flags" suggesting serious underlying conditions.
Key features of each are detailed.

Facial Pain: This covers trigeminal neuralgia (intense, brief attacks of pain), other
facial neuralgias (auriculotemporal, nasociliary, glossopharyngeal), atypical facial
pain, and pain due to temporomandibular joint disorders and dental issues.

Shoulder-Arm and Leg Pain: These sections address conditions involving the
cervical spine, brachial plexus, peripheral nerves, and various musculoskeletal and
vascular causes of arm and leg pain.

IV. Myopathies:

Muscular Dystrophies: This section describes the various types of muscular

dystrophies (Duchenne, Becker, facioscapulohumeral, limb-girdle), detailing their
characteristic progressive muscle weakness, atrophy (sometimes
pseudohypertrophy), and contractures.

Myotonic Syndromes and Periodic Paralyses: This covers the channelopathies

(myotonia congenita, Steinert myotonic dystrophy, periodic paralyses), explaining
their genetic basis and clinical manifestations.
 Metabolic Myopathies: This includes conditions like glycogen storage diseases,
carnitine deficiency, and mitochondrial myopathies, all characterized by exercise-
induced weakness and/or myalgia. Rhabdomyolysis is also discussed.

Myositis: Inflammatory and infectious myopathies (polymyositis, dermatomyositis)

are described, highlighting their clinical features and inflammatory markers.

Myasthenic Syndromes: Myasthenia gravis and Lambert-Eaton syndrome are

discussed, with their differing pathophysiologies (postsynaptic vs. presynaptic
defects in neuromuscular transmission) and clinical features, emphasizing fatigue as
a hallmark symptom. (Mattle & Mumenthaler, 2017)

Diagnosis
I. General Principles:

1. Detailed History-Taking: A complete patient history is crucial, encompassing

current complaints, past medical history, family history, social situation, and lifestyle
factors (including medication use, substance abuse, and occupational exposures).

2. Thorough Neurological Examination: A comprehensive neurological exam, using a

standardized sequence, is considered equally important to the history. This
systematically assesses mental status, cranial nerves, motor function (strength, tone,
coordination), reflexes, sensation, and autonomic function. Specific maneuvers (e.g.,
Romberg test, Lasègue sign, Babinski reflex) are used to localize lesions.

3. Formulation of a Differential Diagnosis: Based on the history and exam, a

clinician creates a list of possible diagnoses, ranked by probability. This list will be
tailored to the patient’s clinical picture.

4. Targeted Ancillary Testing: Ancillary tests (neuroimaging [CT, MRI],

electrophysiology [EEG, EMG, ENG, evoked potentials], laboratory tests [CSF
analysis, blood tests]) are used selectively only when necessary to confirm or refine
the clinical diagnosis and determine etiology, not as a replacement for the initial
clinical assessment.

II. Disease-Specific Diagnostic Approaches (Examples):

The document provides examples of how these general principles are applied to
various diseases:

Multiple Sclerosis (MS): Diagnosis relies on clinical features (disseminated

neurological symptoms over time), MRI (showing scattered lesions), and CSF
analysis (showing oligoclonal bands). The McDonald criteria, which consider both
spatial and temporal dissemination, are mentioned as the current standard.
Differential diagnoses (other inflammatory or demyelinating conditions) are
discussed.

Amyotrophic Lateral Sclerosis (ALS): Diagnosis is primarily clinical, based on a

combination of upper and lower motor neuron signs (weakness, atrophy,
fasciculations, hyperreflexia, Babinski). Ancillary tests are used to rule out other
conditions.

Parkinson's Disease: Diagnosis is made based on the clinical triad (tremor, rigidity,
bradykinesia) and other features, with imaging (CT, MRI) primarily used to rule out
other potential causes (vascular, structural). Olfactory testing might be done to
support a diagnosis of idiopathic Parkinson's disease.

Epilepsy: Diagnosis relies heavily on detailed descriptions of seizure events

(obtained from the patient and witnesses), with the EEG used to detect epileptiform
activity and localize seizure foci. Theres an importance of distinguishing epileptic
seizures from other episodic events (psychogenic seizures, syncope).

Dementia: The diagnostic process emphasizes history-taking (from the patient and
family), a neurological exam, and neuropsychological testing. Imaging studies (MRI,
PET, SPECT) are used to identify possible causes (e.g., Alzheimer's disease,
vascular dementia, Lewy body dementia).

Other conditions: Many other conditions (e.g., specific cranial nerve palsies,
polyneuropathies, myopathies) utilize a similar integrated approach of clinical
assessment followed by targeted ancillary investigations to identify the specific lesion
and determine etiology.

III. Key Ancillary Tests:

Neuroimaging (CT, MRI): Essential for visualizing structural lesions (tumors,

hematomas, infarcts, atrophy), but MRI is often superior for soft tissue detail.
Various MRI sequences (diffusion-weighted, perfusion-weighted, susceptibility-
weighted) are described, providing different information about brain tissue health.

Electroencephalography (EEG): Used to detect epileptiform activity in epilepsy, and

to assess brain activity in altered states of consciousness (coma, delirium).

Electromyography (EMG) and Electroneurography (ENG): These

electrophysiological techniques assess muscle and nerve function, helping
distinguish between myopathies (muscle disease), neuropathies (nerve disease),
and radiculopathies (nerve root disease).

Cerebrospinal Fluid (CSF) Analysis: Provides information about the presence of

inflammation, infection, or bleeding within the CNS. (Mattle & Mumenthaler, 2017)

Treatment

Medical Aspects of ALS:

Pharmacotherapy: Riluzole (glutamate antagonist) prolongs life by 3-6 months;

antioxidants (vitamins E, C, selenium, coenzyme Q, lipoic acid), and creatine
monohydrate may also be used.
Physiotherapy Aspects of ALS:

Maintaining Muscle Strength: The document discusses the ongoing debate about
optimal exercise regimens. It cautions against excessive exertion, which might
accelerate weakness, but also emphasizes the need to prevent atrophy from
inactivity. It recommends a balanced approach involving:

Endurance and Strengthening Exercises: Aerobic conditioning (walking, cycling,

swimming) at submaximal intensity to prevent fatigue. Avoid high-resistance
exercises that excessively fatigue the affected muscles. Progressive overload needs
to be careful.

Neurophysiologically Based Methods: Vojta's reflex locomotion, PNF, and

sensorimotor stimulation are mentioned as useful techniques to activate muscles
and improve coordination, even in cases of significant weakness.

Maintaining Range of Motion: Passive exercises are crucial to prevent contractures,

particularly in the acute stages.

Spasticity Management: Physiotherapy aims to control spasticity through

positioning, passive movements, and the use of neurophysiological techniques to
inhibit spastic patterns. Pharmacological intervention (medication) is considered
only if spasticity significantly hinders rehabilitation.

Management of Secondary Musculoskeletal Changes: Physiotherapy addresses

complications like joint stiffness, muscle contractures, and para-articular ossifications
through mobilization, stretching, and appropriate exercises.

Respiratory Support: Respiratory physical therapy is vital throughout the disease

course, including breathing exercises to improve respiratory function, airway
clearance techniques, and even facilitation of coughing.

Assistive Devices: As the disease progresses, assistive devices such as splints,

orthoses, wheelchairs, and other aids are progressively introduced to compensate
for muscle weakness and maintain independence in activities of daily living.
(Kolář, 2009)

Case report

Patient: A 62-year-old woman is referred to a neurologist by her family physician.

History: The patient has experienced increasing fatigue over several months. More
recently, she has developed muscle cramps and noted difficulty swallowing (food
sometimes "goes down the wrong pipe"). There is no relevant past medical history.

Neurological Examination:

Cranial Nerves: The gag reflex is poorly elicitable. All other cranial nerve findings are
normal.
Speech: Speech is mildly slurred.
Upper and Lower Limbs: Marked, asymmetric muscle atrophy is present in several
muscle groups. Muscle tone is not significantly abnormal. Deep tendon reflexes are
surprisingly brisk, even in the atrophied muscles. Fasciculations are visible. Babinski
signs are weakly present bilaterally. Coordination testing is normal. Sensation is
intact.
Stance and Gait: The patient has significant difficulty standing on her toes and heels
because of weakness.
Other Physical Examination: The patient is in mildly poor overall health with some
nutritional deficits. Blood pressure is slightly elevated. Cardiovascular and other
systemic examinations are otherwise unremarkable.

Diagnostic Reasoning:

The neurologist notes that the patient has muscle atrophy and weakness but no
sensory deficits. This constellation of findings points toward either a myopathy or an
anterior horn cell disease. The presence of fasciculations favors anterior horn cell
disease over myopathy. Diseases of the nerve roots or peripheral nerves would
typically cause both motor and sensory deficits, as well as diminished or absent
reflexes; the brisk reflexes in this patient are inconsistent with those diagnoses. The
combination of anterior horn cell dysfunction (muscle atrophy, weakness,
fasciculations) and upper motor neuron involvement (brisk reflexes, Babinski signs)
is strongly suggestive of amyotrophic lateral sclerosis. Mildly slurred speech points
towards bulbar involvement, which supports the diagnosis further.

Additional Testing (implied but not explicitly described in a single section):

While not explicitly detailed in one place, the diagnostic workup likely would have
included EMG to confirm the presence of denervation and fasciculations and to
distinguish between myopathy and neurogenic disease. Further investigation might
include genetic testing to identify potential hereditary factors. Neuroimaging (MRI)
could have been used to rule out other causes of the symptoms.

Diagnosis: Amyotrophic Lateral Sclerosis (ALS)

(Mattle & Mumenthaler, 2017)

Bibliography:
Grad, L. I., Rouleau, G. A., Ravits, J., & Cashman, N. R. (2017). Clinical Spectrum of
Amyotrophic Lateral Sclerosis (ALS). Cold Spring Harbor Perspectives in
Medicine, 7(1), a024117. https://doi.org/10.1101/cshperspect.a024117

Mattle, H., & Mumenthaler, M. (2017). Fundamentals of neurology: An illustrated

guide (2nd ed.). Thieme.

Kolář, P., Kučera, M., Lewit, K., & Petrášek, J. (2009). Clinical
rehabilitation. Prague, Czech Republic: Alena Kobesová.