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

Thank You