Autoimmune Epilepsies Azhar Daoud, MD, FRCP Professor and Consultant in Child Neurology, Specialty...
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Transcript of Autoimmune Epilepsies Azhar Daoud, MD, FRCP Professor and Consultant in Child Neurology, Specialty...
Autoimmune EpilepsiesAzhar Daoud, MD, FRCP
Professor and Consultant in Child Neurology, Specialty Hospital, Amman, Jordan
Indications for the role of immunityin epilepsies
Anticonvulsant activity of steroidsFever and infection exacerbate seizuresSeizures frequency in autoimmune
diseasesDetection of autoantibodies in certain
epilepsiesSeizures aggravated by vaccinations
Autoimmune epilepsies
ACTH and steroid in infantile spasmInflammation appear to have a central
mechanism in certain experimental modules of epilepsy.
Inflammation produce cascade of molecules against exogenous pathogen
Autoantibodies also have a role in inflammation, hashimotos encephalopathy
Possible aetiology
Antibodies directed against molecules on the neural surface, e.g. N-methyl-D-aspertate receptor (NMDA-R) or the voltage gated potassium channel(VGKC) complex
Underlying mechanism of Rasmussen syndrome is chronic and progressive inflammation
Acute inflammation and cytokine cascade activation is important in status epileptics
Examples of autoimmune epilepsies
Dravet syndrome where fever trigger long duration of seizures
In some children with sever epilepsies, fever induces periods of seizures freedom
Idiopathic hemiconvulsion-hemiplegia syndrome (IHHS) and FIRES have clear relation to infection.
Epilepsies caused by autoantibodies related conditions
Limbic encephalopathy and temporal lobe seizures (subacute onset of sever memory impairment and mood disturbance with recurrent temporal lobe seizures)
Onconeural antibodies directed against the intracelullar protein Hu,Ma ½,amphiphysin,or CV2 and can be associated with tumors
Antibodies against VGKC
Limbic Encephalopathies
Some time associated or preceded by fasiobrachial dystonic seizures
MRI, medial temporal changesElevated serum VKGC antibody titer
confirm the diagnosisRespond to intravenous immunoglobulin
or corticosteroids
Encephalopathy with NMDAR antibodies
Acute psychiatric disorders(delirium, visual or auditory delusions, aggression and irritability) and epileptic seizures, usually of extratemporal origin, initial phase followed by
Sever phase choreoathetoid movement disorders, dysautonomia and impaired consciousness
Autoantibodies against NMDARs
Epileptic Encephalopathy
Recent data show up to 45% associated with tumors
Brain MRI are normal in 50%CSF show inflammation in 90% of case
with or without oligoclonal bandsEEG abnormal in 90% of caseImmunotherapy is effective in 50%
Epilepsies with inflammationChronic inflammation
Rasmussen’s encephalitis, hemispheric brain inflammation leading to unilateral brain atrophy, viral infections
Pharmacoresistant focal seizures, progressive unilateral motor deficit and cognitive decline
Cell mediated immunity of cytotoxic T cellsImmunosuppressive before surgery
Epilepsies with possible Acute inflammation
IHHS, febrile seizures followed by hemiplesia started as flaccid before becoming progressively spastic
First 2 year of lifeIn preexisting brain disorder, SW, TS,
corpus callosum agenesis but some time in normal healthy children
CSF normal nor oligoclonal banding
IHHS
Fever trigger status epileptics, clonic jerks or head and eye deviation, predominant in one side and last for several hours
EEG high amplitude 2-3Hz rhythmic slow wave activity contra lateral to hemiclonic jerks.
¾ of them have persistent epilepsyMRI, unilateral edematous swelling
followed by hemiatrophy
Conclusion
The finding of inflammatory markers and especially autoantibodies in several epileptic disorders of unknown etiology has open up a group of possible causes and investigations in epilepsies.
New immunosuppressive and immunomodulatoey treatment for certain epilepsies
Concern
This finding raise many questionsHow to classify these disordersThe relationship of antibodies and specific
clinical phenotypesThe mechanism of generation of these
autoantibodies Optimum treatment strategiesKetogenic diet efficacy