الفهرس 
IntroductionOnly 14 pages are availabe for public view
 |  | from | 163 |  |  |
| | | from | 163 | | |
Abstract
Autoimmunity is increasingly being recognized as a cause of epilepsy. The autoimmune epilepsies are immunologically mediated disorders in which recurrent seizures are a primary and persistent clinical feature. When other etiologies have been excluded, an autoimmune etiology of epilepsy is suggested in the presence of resistance to ASMs. In such patients, immunotherapy may be highly effective, depending on the particular autoimmune epilepsy syndrome present.
The International League Against Epilepsy (ILAE) classification of the epilepsies currently classifies autoimmune epilepsy as “focal epilepsy with immune etiology”. The seizures in autoimmune epilepsy patients may occur as one of a number of other CNS manifestations of an autoimmune encephalitis syndrome which, if recognized, aids diagnosis. However, in some patients, seizures are the primary symptom and other features of encephalitis are lacking, which can cause delays in recognition.
Most patients with autoimmune epilepsy present with seizures of recent onset, and seizure frequency that is characteristically high from their inception and sometimes rapidly escalating to status epilepticus. The seizures in autoimmune epilepsy usually do not respond to ASMs therapy and therefore quickly declare themselves as drug resistant. Given the resistance to ASMs and potential definitive response to immunotherapy, rapid diagnosis is important.
Some cases of AE are associated with specific autoantibodies to a number of structures, including cell surface molecules as well as intracellular targets. However, it is common for antibody testing to return negative, in such case clinicians must make a diagnosis based on a combination of clinical phenotypes and other supportive investigations rather than solely on antibodies testing. So, recognition of the clinical, CSF, EEG and MRI features, and familiarity with diagnostic criteria and clinical scoring systems, facilitates diagnosis and early start of immunotherapy in those patients.
A number of immunotherapy regimens are currently utilized, and most involve corticosteroids, IVIG and plasma exchange as first-line treatments. chronic maintenance immunotherapy with second line immunotherapy is usually recommended for those experiencing a significant response to initial treatment. The goals of chronic immunosuppressant therapies are to augment and sustain the effect of initial immunotherapy, and to prevent relapses, which occur in one-third of patients. The duration for which maintenance immunotherapy should be continued is unresolved at the present time, yet withdrawal of immunotherapy can be considered after 2 years relapse free. Application of therapies targeting specific steps in the immune response will likely play an expanding role in future management.
Although intractability is a common feature in AE, some patients respond to ASMs, and they remain an important aspect of therapy. Some ASMs alone were effective in controlling seizures and resulted in seizure freedom in a few cases of AE patients, particularly those with sodium channel blocking properties. This suggests a potential anti-inflammatory mechanism as a cause of higher efficacy of sodium channel blockers seen in AE. Yet, prospective studies are needed to clarify ASMs selection and to illustrate their immunomodulatory properties in AE
The current study assessed the presence of NMDA-R, AMPA1-R, AMPA2-R, GABAB-R, CASPR-R, LGI-R and GAD65 autoantibodies in a sample of Egyptian patients with new onset drug resistant epilepsy, together with the clinical, cerebrospinal fluid, electroencephalogram, and radiological characteristics of those patients.
Methodology:
This is an observational pilot study that was approved by the Ethical Review Committee, Ain Shams University (FMASU MD 274/2019). The study included a sample of 25 drug resistant epilepsy patients recruited from the department of Neurology at Ain Shams University Hospitals. All were fulfilling the criteria.
Patients were subjected to full clinical assessment including Full history taking regarding age, family and past history including autoimmune diseases and neoplasia, history of present illness including, age at seizure onset, duration of illness, seizure semiology and frequency, seizure associated symptoms, latency from onset to diagnosis and treatment, received ASMs and immunosuppressive therapies and outcome after completion of immunotherapy trial.
All patients underwent serum and CSF antibody testing, samples were sent to the Immunology Unit at the Clinical pathology laboratory of Ain Shams University Hospitals and tested for (Anti-NMDA-R - Anti-AMPA1-R - Anti-AMPA2-R - Anti-CASPR2-R - Anti-LGI1-R - Anti-GABAB-R - Anti-GAD 65) neuronal antibodies using cell-based assay. This is beside routine CSF analysis, EEG and MRI brain.
Results
Demographic data and medical history
The mean age of patients was 31.200 ± 17.229 years. Fifteen (60%) patients were males, while 10 (40%) patients were females.
Sixteen (64%) patients were medically free. Five (20%) patients had history of chronic medical illnesses. Three (12%) patients had history of autoimmune disorders, one patient was diagnosed with behcet’s disease, another was diagnosed as autoimmune thyroiditis and the third had rheumatoid arthritis. One (4%) patient discovered to be Hodgkin lymphoma at follow up, 2 months after being diagnosed anti-GAD 65 positive.
None of the patients had family history of epilepsy, 1 (4%) patient had family history of psoriatic arthritis in mother, and 1 (4%) patient had family history of breast cancer in mother.
Clinical data:
The first presenting symptom was seizures refractory to conventional ASMs in 19 (76%) patients, Seizure-associated symptoms were psychiatric changes in 12 (48%) patients, cognitive dysfunction in 8 (32 %), movement disorder in 5 (20 %) and dysautonomia in 2 (8 %) patients.
Eleven (44%) patients were presented with focal to bilateral tonic clonic seizure, 6 (24 %) patients were presented by generalized seizure type, 5 (20 %) patients had focal motor onset seizures, 3 (12 %) patients had focal seizures with impaired awareness, and only 1 (4 %) patient had focal non motor onset seizure. Patients had high seizure frequency, 14 (56%) patients had seizures daily, 4 (16%) patients developed status epilepticus and 2 (8%) patients had refractory status epilepticus and needed ICU transferal to start anesthesia.
Electroencephalography:
Three (12 %) patients had normal EEG, 12 (48 %) patients had focal epileptiform activity with/without secondary generalization, 6 (24 %) patients had slowing, 4 (16 %) patients had generalized epileptiform activity, 2 (8 %) had PLEDs, 2 (8 %) had extreme delta brush and only 1 had diffuse dysrhythmia.
Radiological data:
MRI brain was normal in 7 (28 %) patients, 9 (36 %) patients had T2/Flair hyperintense lesions in temporal lobe in their MRI, 6 (24 %) patients had hyperintense lesions involving two or more brain regions, while 3 (12 %) patients had non-specific T2/Flair hyperintensities.
Laboratory data:
One (4%) patient tested positive to anti-NMDA antibodies and another one (4%) tested positive to anti-GAD 65 in both serum and CSF. Routine CSF analysis was normal in 8 (32%) patients, while 14 (56%) patients had elevated proteins, 4 (16%) patients had positive oligoclonal bands, 3 (12%) patients had increased IgG index and 2 (8%) patients had elevated lymphocytes.
Antiseizure medications and immunotherapy:
Carbamazepine, Phenytoin, Valproate, Levetiracetam, Lacosamide, Oxcarbazepine, Zonisamide, were the most frequently used ASMs in 16 (64 %), 14 (56 %), 12 (48 %), 8 (32 %), 7 (28 %), 6 (24 %) and 5 (20 %) patients, respectively. And to lesser extent Topiramate, Clonazepam, Eslicarbazepine and Lamotrigine in 4 (16 %), 4 (16 %), 4 (16 %) and 3 (12 %) patients, respectively.
Regarding immune therapy, 20 (80%) patients received IVMP, 6 (24%) patients had plasma exchange, 5 (20%) received IVIg, 2 (8%) patient received oral prednisolone, and 3 (12%) patients didn’t receive any immunomodulatory treatment.
Outcome:
Fourteen (56%) patients achieved seizure freedom and 9 (36%) patients had more than 50% reduction in seizure frequency after a mean of 48.34 ± 13.64 days from the start of ASMs and 19.82 ± 6.14 days from the start of immunotherapy. Also, seizure associated symptoms improved markedly in 84% of the patients.
In conclusion, it is important to consider autoimmunity in the differential diagnosis of new onset refractory epilepsy. Autoimmune epilepsy is a reversible condition with a rapid response to immunotherapy. When clinical, serological and radiological clues suggest an autoimmune basis for medically intractable epilepsy, early initiated immunotherapy is crucial. Besides management, immunotherapy responsiveness plays a major role in the diagnosis of autoimmune epilepsy, especially in seronegative cases.