الفهرس 
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Abstract
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UMMARY
pilepsy is a neurological disorder characterized by sudden recurrent episodes of convulsions, sensory disturbance, or loss of consciousness, resulting from abnormal electrical brain activity. According to The International League against Epilepsy, the condition is defined by at least 2 unprovoked seizures more than 24 hours apart. More than 70 million people worldwide are affected by this disorder.
Epilepsy can have both genetic and acquired causes, with interaction of these factors in many cases. Acquired causes include severe brain trauma, stroke, tumors and problems in the brain as a result of a previous infection. In about 60% of cases the exact cause is unknown. In addition, auto-antibodies against synaptic receptors have been detected in a number of neurological conditions such as anti-NMDA receptor encephalitis and limbic encephalitis.
Anticonvulsant medications are the cornerstone of epilepsy treatment, which may continue for lifetime of the patient. Initially, a single medication is recommended; if control is not achieved, changing to a single other medication is recommended. If the second medication fails, two medications at once are recommended then. Failure of adequate trials of two tolerated and appropriately chosen and used antiepileptic drugs to achieve sustained seizure freedom is known as drug-resistant epilepsy.
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In recent years, three types of synaptic receptors have been the subject of research in regarding their role in the normal physiology of the nervous system, and their involvement in various neurological conditions. These receptors include AMPA receptors, NMDA receptor receptors and GABAB receptors. It is possible that antibodies directed against these receptors maybe the underlying cause of many drug resistant epilepsy cases.
AMPA receptors play an important role in the generation and spread of epileptic seizures. In the early 90s, antibodies against AMPA receptors have been identified in Rasmussen encephalitis. In the following years, more studies have shown that Anti-AMPA antibodies were not exclusive to RE, but found in patients with severe drug resistant epilepsy. Further studies have shown the presence of anti-AMPA antibodies in limbic encephalitis. Promising results over the years have been obtained in a relatively small number of epilepsy patients with anti-AMPA-GluR3 antibodies, with regard to their responses to immunotherapy of various modalities. In such cases, treatment of epilepsy patients that had anti-AMPA-GluR3 antibodies with repeated plasmapheresis, Intravenous Immunoglobulins (IVIG) or long-term selective IgG immunoadsorption, resulted in a transient reduction in seizure frequency and also a marked improvement in neurological function, along with reduced serum titers of the anti-AMPA-GluR3 antibodies.
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The NMDA receptor channels play a key role in synaptic plasticity and synapse formation responsible for memory, learning and formation of neural networks during CNS development. Overactivation of these receptors, causing excessive influx of Ca2+ can result in excitotoxicity which is thought to be involved in various neurodegenerative disorders. Antibodies against NMDA receptors have also been detected in neurological conditions presented by seizures, most importantly Anti-NMDA encephalitis. Many patients with „Anti-NMDA receptor Encephalitis‟, that have anti-NMDA-NR1 antibodies in their serum and CSF were treated with either first-line immunotherapy: Steroids, IVIG, or plasmapheresis/plasma exchange, or with second-line immunotherapy: Rituximab or Cyclophosphamide or both. Many of these cases, these immunotherapies helped achieve marked recovery, and were correlated with a decrease in the titers of the anti-NMDA-NR1 antibodies.
GABA receptors are a class of receptors that bind to the neurotransmitter gamma-amino butyric acid (GABA), the chief inhibitory neurotransmitter in the CNS. Autoimmune encephalitis associated with antibodies against GABAB Receptors in patients with limbic encephalitis was first stated in 2010. Further studies in the following years have demonstrated that patients with anti-GABAB R antibodies develop Limbic Encephalitis with prominent epilepsy, which is usually resistant to multiple anti-epileptic agents and responds to
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immunotherapy. Most patients with anti-GABABR encephalitis present with limbic encephalitis with prominent seizures. Almost all patients respond, completely or partially, to immunotherapy or a combination of immunotherapy and tumor treatment, demonstrating the significance of early diagnosis and treatment.
In our study, we aim to determine whether autoantibodies against AMPA, NMDA and GABAB receptors are present in drug-resistant epilepsy and their correlation with clinical and electrophysiological findings.
The study was conducted in the Immunology unit, Department of Clinical Pathology, Ain Shams University hospital. A total of 17 epilepsy patients were sampled for both CSF and Blood; with 12 males and 5 females. The patient age range was from 13 years up to 63 years, with the median age of 23 years. The duration of the illness ranged from 1 month to 7 months, with the median duration of 3 months. All patients will be subjected to full history taking including age, family history and previous medications, Electroencephalography, Indirect immunofluorescence on serum and cerebrospinal fluid (CSF) for anti-AMPA, anti-NMDA and anti-GABAR antibodies. Each slide slides with 5 test fields contained EU 90 transfected cells with the corresponding Antigen substrate for each antibody. Diluted serum was applied to each reaction field of the reagent tray.
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Regarding Anti-AMPAR antibodies, none of the 17 cases tested for in both serum and CSF were positive. As for Anti-NMDAR antibodies, only one (1) CSF sample tested positive for Anti-NMDAR antibodies, while the serum sample for the same patient tested negative. This patient‟s sample was positive despite 7 sessions of pulse steroid therapy, five sessions of plasmapharesis and intravenous immunoglobulins, after that his condition dramatically improved. This may prove beneficial since the detection of the antibody for diagnostic purposes might not be affected by treatment protocols, even if the general condition improves. Finally regarding Anti-GABABR antibodies, none of our patients demonstrated Anti-GABAB anitbodies in either serum or CSF.
There are various factors which may have contributed to the difference of our results from other similar studies. First of all, the low number of patient sample collected for the study compared to other researches done in this topic. Also, the genetic composition of the cases studied and how autoimmune diseases occur in different ethnic groups. In addition, the indirect immunofluorescence technique used in our study using EU-90 transfected cells is very specific. The high specificity of this technique may attribute to the low outcome of positive cases in our study, since the prevalence of false positive cases is virtually non-existent. Furthermore, the absence of specialized medical centers in Egypt that deal with autoimmune epilepsy cases in particular may be an interfering factor while
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conducting studies in this branch of researches. Finally, the high cost of this test is an obstacle in performing it for a large number of suspected patients.
We recommend a larger number of drug-resistant epilepsy cases to be investigated for a longer period of time to identify the possible significance of detected autoantibodies. Further studies are also recommended to verify the presence of any other autoantibodies such as Anti-LGI1, Anti-CASPR2 and Anti-DPPX. Finally, the establishment of specialized centers for diagnosis and assessment of immune-mediated epilepsy and autoimmune encephalitis may help provide great benefits for patients suffering from such conditions