IntractableEpilepsy PDF
IntractableEpilepsy PDF
IntractableEpilepsy PDF
EPILEPSY: NEW
OPTIONS IN 2012
Allan Krumholz, MD; Department of
Neurology, University of Maryland School
of Medicine; Baltimore VA Epilepsy Center
of Excellence
EPILEPSY
NATURAL HISTORY OF
EPILEPSY
PREDICTORS OF EPILEPSY
INTRACTABILITY
Total dependence
on others for
support
21%
Sillanp, 1990.
Complete financial
and social
independence
61%
Early remission
3%
Intractable
79%
Begley, 2000.
ANTIEPILEPTIC
MEDICATIONS
EPILEPSY SURGERY
NEURO-STIMULATION
RADIATION THERAPY
IMMUNOTHERAPY
GENETIC THERAPIES
PSYCHOLOGICAL/
SOCIAL
INTERVENTIONS
ANTIEPIELEPTIC
MEDICATIONS
B. Focal Seizures
Without impairment of
consciousness (motor,
sensory, autonomic)
With impairment of
consciousness (evolving to
bilateral convulsive)
D. Unknown
Focal Epilepsy
Antiepileptic
Medications
Phenytoin-Dilantin.
Phenobarbital.
Carbamazepine-Tegretol.
Valproate- Depakote.
Ethosuximide- Zarontin
Primidone - Mysoline.
Benzodiazepines- Klonopin
Acetazolamide-Diamox
Lacosamide Vimpat*
Clobazam Frisium**
Felbamate - Felbatol.
Gabapentin - Neurontin.
Lamotrigine -Lamictal.
Topiramate-Topamax
Tiagabine - Gabatril.
Levetiracetam.- Keppra
Zonisamide-Zonegran
Oxcarbazepine- Trileptal.
Pregabalin - Lyrica
Rufinamide Banzel*
Vigabatrin Sabril*
Ezogabine Potiga**
Third Line
First Line
Second Line
lamotrigine
gabapentin
carbamazepine
oxcarbazepine
levetiracetam
phenytoin
valproate
zonisamide
topiramate
tiagabine
phenobarbital
VNS
felbamate
methsuximide
clonazepam
ethosuximide
ketogenic diet
14
Best
Lamotrigine
Levetiracetam
Valproate
Felbamate
Gabapentin
Lacosamide
Relatively Good
Carbamazepine
Phenytoin
Oxcarbazepine
Intermediate
Tiagabine
Zonisamide
Least Favorable
Phenobarbital
Primidone
Topiramate
EPILEPSY SURGERY
Intractable epilepsy
Present for a substantial duration (usually years)
Refractory to medical therapy
Substantially impairing quality of life
Benefit of surgery should outweigh the risks
HETEROTOPIAS
PET
Depth electrodes
Cortical grids or strips
Ictal SPECT scans
Nuclear magnetic resonance
scans
Magnetoencephalography
Temporal lobectomy
Extratemporal resections (lobar:
frontal, occipital)
Corpus Callosotomy
Hemispherectomy
Multiple subpial transections
20%
10%
0%
Sz-Free
Medical
Surgical
NEUROSTIMUATION
1970s - Cerebellar
stimulation
1990s to today - Vagus
Nerve Stimulation
(VNS)
1980s and perhaps (?)
again Deep Brain
(Thalamic) Stimulation
(DBS)
Reactive Neural
Stimulation (RNS)
Neurostimulation
Desynchronization of EEG
Suppression of spikes
Block ictal rhythmic build-up in a seizure
Release of GABA and Glycine
Effects on limbic and brainstem systems
Investigational Neurostimulation
Responsive Neurostimulation
Sun FT et al. Responsive cortical stimulation for the treatment of epilepsy. Neurotherapeutics 2008;5:68-74.
Responsive Neurostimulation
Responsive Neurostimulation
Seizure Detection - Examples
Stimulation Effect
Sun FT et al. Responsive cortical stimulation for the treatment of epilepsy. Neurotherapeutics 2008;5:68-74.
Responsive Neurostimulation
Gamma
Knife
Target is the
Temporal
Lobe
Neurocysticercosis
Viral encephalitis (herpes, EB,
rotovirus, etc.)
Mycoplasma pneumoniae
Syphilis
Chronic meningitis
Autoimmune
LIMBIC ENCEPAHLITIS
AUTOIMMUNE REFRACTORY
EPILEPSIES
Limbic encephalitis
Anti-NMDA receptor encephalitis
Antiglutamate receptor encephalitis
Voltage Gated Potassium Channel (VGPK) Antibodies
Anti-glycolipid antibody syndrome
Hashimotos encephalopathy (autoimmune thyroid
encephalopathy)
IMMUNSUPPRESSIVE
THERAPIES FOR REFRACTORY
EPILEPSIES
Corticosteroids
Intravenous immunoglobulin
Plasma exchange
Cyclophosphamide
Calcineurin antagonists
INTRACTABLE EPILEPSY:
GENETIC IMPLICATIONS
Epilepsy control
Some genetic epilepsies respond
best to specific AEDs (e.g.
ADNLE to CBZ ; JME to VPA)
21 genes associated with
idiopathic generalized epilepsy
channelopathies- Na , Ca, K, Cl
channels; GABA and Ach
receptors
Neuronal migration disorders
(e.g. Lissencephaly (LIS1, DCX)
POTENTIAL GENETIC
THERAPIES
Diagnose properly
Medical therapy
Education and support
Pyschosocial RX
Epilepsy surgery, etc
Maximize patients
adjustment and coping
strategies
CONCLUSIONS
INTRACTABLE
EPILEPSY: NEW
OPTIONS IN 2012
Allan Krumholz, MD; Department of
Neurology, University of Maryland School
of Medicine; Baltimore VA Epilepsy Center
of Excellence