The Evolving Standard of Care for Autoimmune Neuropsychiatric Illness.

In recent decades, there has been increasing biomedical and public understanding of the role of autoimmunity in neuropsychiatric illness. Popular media have highlighted patients with psychiatric illnesses who were eventually diagnosed with autoimmune neuropsychiatric illnesses such as anti- N-methyl-D-aspartate receptor encephalitis. Coverage of these cases has often drawn attention to the effects of misdiagnosis or delayed diagnosis of such diseases in psychiatric patients. Autoimmune encephalitis can have varied presentations and often involves evaluation and management from multiple medical specialties. As a result, there remains considerable uncertainty regarding how courts might gauge the legal standard of care with regard to psychiatric workup of new-onset psychiatric symptoms, and the degree to which autoimmune encephalitis must be considered. In this article we provide a brief overview of autoimmune encephalitis and autoimmune psychosis, including current diagnostic approaches to these conditions. We review case law regarding the standard of care for psychiatric disorders caused by general medical conditions. Finally, we provide a medicolegal perspective on the responsibilities of psychiatrists and other mental health professionals in the evaluation of possible autoimmune encephalitis.

Reversible encephalitis-like episodes in fragile X-associated tremor/ataxia syndrome: a case report.

BACKGROUND: Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder caused by CGG repeat expansion of FMR1 gene. Both FXTAS and neuronal intranuclear inclusion disease (NIID) belong to polyglycine diseases and present similar clinical, radiological, and pathological features, making it difficult to distinguish these diseases. Reversible encephalitis-like attacks are often observed in NIID. It is unclear whether they are presented in FXTAS and can be used for differential diagnosis of NIID and FXTAS. CASE PRESENTATION: A 63-year-old Chinese male with late-onset gait disturbance, cognitive decline, and reversible attacks of fever, consciousness impairment, dizziness, vomiting, and urinary incontinence underwent neurological assessment and examinations, including laboratory tests, electroencephalogram test, imaging, skin biopsy, and genetic test. Brain MRI showed T2 hyperintensities in middle cerebellar peduncle and cerebrum, in addition to cerebellar atrophy and DWI hyperintensities along the corticomedullary junction. Lesions in the brainstem were observed. Skin biopsy showed p62-positive intranuclear inclusions. The possibilities of hypoglycemia, lactic acidosis, epileptic seizures, and cerebrovascular attacks were excluded. Genetic analysis revealed CGG repeat expansion in FMR1 gene, and the number of repeats was 111. The patient was finally diagnosed as FXTAS. He received supportive treatment as well as symptomatic treatment during hospitalization. His encephalitic symptoms were completely relieved within one week. CONCLUSIONS: This is a detailed report of a case of FXTAS with reversible encephalitis-like episodes. This report provides new information for the possible and rare features of FXTAS, highlighting that encephalitis-like episodes are common in polyglycine diseases and unable to be used for differential diagnosis.

Listeria monocytogenes: a rare cause of rhomboencephalitis in an immunocompetent patient.

We present an unusual case of Listeria monocytogenes rhomboencephalitis in a young, healthy patient. Although L. monocytogenes meningitis is usually associated with immunodeficiency, rhomboencephalitis is more commonly seen in immunocompetent patients. The wide differential for rhomboencephalitis can create a diagnostic challenge. Without prompt pathogen identification and appropriate antibiotic regimen, L. monocytogenes central nervous system infections can be fatal. Cerebro-Spinal Fluid (CSF) Polymerase Chain Reaction (PCR) aided a prompt diagnosis and adjustment of therapy to achieve a good patient outcome.

Cerebellar syndrome as the presenting feature of Hashimoto encephalopathy.

Hashimoto encephalopathy presents with a myriad of neuropsychiatric features in the background of elevated antithyroid antibodies and it may or may not be associated with Hashimoto thyroiditis. It is a diagnosis of exclusion. Here, we present the case of a hypothyroid woman in her 30s, with a 5-year history of chronic progressive gait ataxia along with hand and head tremor, inattention and electroencephalogram (EEG) suggestive of interictal epileptiform discharges without any clinical seizures. The patient had very high titres of anti-thyroid peroxidase antibodies >2000 IU/mL and was on very high-dose levothyroxine replacement therapy. She responded to intravenous pulse corticosteroids. Improvement was noted both clinically and on subsequent EEGs. Pure cerebellar syndrome without frank encephalopathy can also be a rare presentation of Hashimoto encephalopathy. This highlights the importance of antithyroid antibodies testing even in cases of pure cerebellar syndrome to rule out Hashimoto encephalopathy associated ataxia.

Management of Autoimmune Encephalitis in a 7-Year-Old Child With CTLA-4 Haploinsufficiency and AMPA Receptor Antibodies: A Case Report.

OBJECTIVES: We report on the therapeutic management of early-onset severe neurologic symptoms in cytotoxic T lymphocyte antigen-4 haploinsufficiency (CTLA-4h) and the presence of antibodies to the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) as an important finding. METHODS: This is a case report from a Dutch academic hospital. Repeated clinical examinations, repeated brain MRI and extended diagnostics on serum and CSF were performed. We used the CARE checklist. RESULTS: A 7-year-old boy was diagnosed with CTLA-4h based on family screening. On diagnosis, he had mild chronic diarrhea and autism spectrum disorder, but no abnormalities in extensive laboratory screening. Six months later, he presented with sudden-onset autoimmune encephalitis. Repeated brain MRI revealed no abnormalities, but immunohistochemistry analysis on serum and CSF showed the presence of AMPAR antibodies. Treatment was initially focused on immunomodulation and targeted CTLA-4 replacement therapy. Because of the persistent fluctuating cerebellar and neuropsychiatric symptoms and the potential clinical significance of the AMPAR antibodies, treatment was intensified with repetition of first-line immunomodulation and rituximab. This combined therapy resulted in sustained clinical improvement and served as a bridge to curative hematopoietic stem cell transplantation. DISCUSSION: This case illustrates the rare early onset of autoimmune encephalitis and presence of AMPAR antibodies in CTLA-4h. Targeted CTLA-4 replacement therapy resulted in a partial response. However, awaiting its optimal therapeutic effect, refractory CNS symptoms required intensification of immunomodulation. The identification of AMPAR antibodies guided our treatment decisions. CLASSIFICATION OF EVIDENCE: This provides Class IV evidence. It is a single observational study without controls.

Autoimmune encephalitis in glial fibrillary acidic protein astrocytopathy.

Autoimmune encephalitis due to glial fibrillar acidic protein (GFAP) astrocytopathy is a rare cause of subacute neuropsychiatric changes. In this case, a young patient presented with a viral prodrome and meningismus, followed by progressive encephalopathy and movement disorders over the span of 2 weeks. Due to his clinical trajectory, inflammatory cerebrospinal fluid (CSF) analysis, initial normal brain imaging and negative serum autoimmune encephalopathy panel, his initial diagnosis was presumed viral meningoencephalitis. The recurrence and progression of neuropsychiatric symptoms and myoclonus despite antiviral treatment prompted further investigation, inclusive of testing for CSF autoimmune encephalopathy autoantibodies, yielding a clinically meaningful, positive GFAP autoantibody. This case highlights the importance of appropriately testing both serum and CSF autoantibodies when an autoimmune encephalitic process is considered. Through this case, we review the clinical and radiographic manifestations of GFAP astrocytopathy, alongside notable pearls pertaining to this autoantibody syndrome and its management.

Mimickers of autoimmune encephalitis: a literature review.

Autoimmune encephalitis (AIE) is a rapid, progressive neurological disorder characterized by nervous system inflammation. While the Graus criteria are the best known criteria for AIE diagnosis, other differential diagnoses meeting the Graus criteria must be considered before management. This narrative review discusses the most common etiologies that resemble AIE. We suggest routine exclusion of mimickers meeting the Graus criteria before confirming an AIE diagnosis. We reviewed 28 studies including 356 patients. The main initial diagnosis was AIE, then paraneoplastic limbic encephalitis and anti-N-methyl-D-aspartate receptor encephalitis. Only 194 patients met the possible Graus criteria. The most frequent conditions among the total population were dementia, other neurodegenerative diseases, and psychiatric and functional neurological disorders. AIE is often misdiagnosed, leading to unnecessary treatment. Despite publication of the Graus criteria, medical cases mimicking this condition are being published. Many neurological diseases entering the differential diagnosis of AIE could be excluded through a detailed history, neurological examination, laboratory analysis, and other investigations, including cerebrospinal fluid and brain magnetic resonance imaging. However, some differential diagnoses complied with the possible Graus criteria, with some having concurrent antineuronal antibodies, which were considered true mimickers. AIE diagnosis suspicion is primarily clinical, but a definitive diagnosis requires various diagnostic tools.

LGI1-antibody encephalitis: how to approach this highly treatable dementia mimic in memory and mental health services.

Leucine-rich glioma-inactivated 1-antibody-encephalitis is a treatable and potentially reversible cause of cognitive and psychiatric presentations, and may mimic cognitive decline, rapidly progressive dementia and complex psychosis in older patients. This aetiology is of immediate relevance given the alternative treatment pathway required, compared with other conditions presenting with cognitive deficits.

Could Cerebral Inflammatory Lesions be the Cellular Origin of Primary Central Nervous System Lymphoma?

INTRODUCTION: Primary central nervous system lymphoma (PCNSL) presents a diagnostic enigma due to the inherent absence of lymphoid tissue in the central nervous system (CNS). The hypothesis posits that lymphocytes infiltrating the CNS during inflammatory responses could represent a cellular source for PCNSL, challenging traditional understandings of its etiology. PATIENT CONCERNS: In 2 illustrative cases, patients presented with neurological symptoms initially misdiagnosed as encephalitis and demyelinating disease, respectively. These diagnoses were established based on clinical assessments and initial biopsy findings. DIAGNOSIS: Subsequent biopsies, conducted months after the first signs of disease, confirmed the diagnosis of PCNSL in both patients. Identifying CD20-positive tumor cells was pivotal, indicating a B-cell lymphoma origin. INTERVENTIONS: Treatment strategies included high-dose methotrexate chemotherapy for both patients. In addition, the second patient underwent adjuvant whole-brain radiotherapy after the chemotherapy regimen. OUTCOMES: The therapeutic approach significantly reduced tumor size in both cases, with no evidence of recurrence observed during the follow-up period. This outcome underscores the potential efficacy of the chosen interventions. CONCLUSION: In response to inflammatory lesions, lymphocyte infiltration into the CNS may serve as a pivotal origin for tumor cells in PCNSL. These cases highlight the complexity of diagnosing CNS disorders and suggest that various forms of encephalitis in the early stages could influence the prognosis of lymphoma. This insight into the cellular origins and treatment responses of PCNSL contributes to a broader understanding of its pathophysiology and management.

Molecular detection of Sarcocystis sp. in a kept under human care black capuchin monkey (Sapajus nigritus., Goldfuss 1809) with necrotizing encephalitis.

A senile male black capuchin monkey (Sapajus nigritus) kept under human care in a Zoo was found dead after 2 weeks presenting signals of weight loss and hyporexia. Histopathological revealed a necrotizing encephalitis. Although it was not observed microscopically, Sarcocystis sp infection was detected in brain tissue from molecular assays. These infections have been rarely described in neotropical primates, particularly associated with tissue lesions.

Case report: Shingles-associated probable Bickerstaff brainstem encephalitis with IgM anti-sulfatide positivity.

Background: Bickerstaff brainstem encephalitis (BBE) is a rare disease considered caused by acute demyelination of the brainstem, most often resulting from secondary autoimmune responses. To our knowledge, this is the first probable case report of shingles-associated BBE with anti-sulfatide IgM positivity. Case presentation: We report the case of an 83-year-old woman with symptoms of progressive limb weakness, difficulty swallowing food, and disturbed consciousness that occurred 4 weeks following herpes zoster infection. Autoimmune anti-sulfatide antibodies were positive and fluid-attenuated inversion recovery (FLAIR) sequences revealed clear high signal intensity in pons and bilateral thalamus. Our patient's condition improved markedly with glucocorticoid treatment. After 2 months of treatment, our patient was fully recovered. We considered that for her case, BBE is the most appropriate diagnosis. Conclusions: We emphasize the importance of a careful medical history and assessment of clinical symptoms, performing MRI, testing autoimmune antibodies for rapid diagnosis, and ruling out differential diagnoses. Further studies involving more patients with BBE with IgM anti-sulfatide autoantibodies will increase the understanding of the clinical characteristics and advance the diagnosis and treatment of this syndrome. Meanwhile, it is crucial for dermatologists to know about this severe neurological complication following shingles.

Cardiopulmonary Coupling Spectrogram as an Ambulatory Method for Assessing Sleep Disorders in Patients With Autoimmune Encephalitis.

BACKGROUND AND OBJECTIVES: Sleep disorders are a common and important clinical feature in patients with autoimmune encephalitis (AE); however, they are poorly understood. We aimed to evaluate whether cardiopulmonary coupling (CPC), an electrocardiogram-based portable sleep monitoring technology, can be used to assess sleep disorders in patients with AE. METHODS: Patients fulfilling the diagnostic criteria of AE were age- and sex-matched with recruited healthy control subjects. All patients and subjects received CPC testing between August 2020 and December 2022. Demographic data, clinical information, and Pittsburgh Sleep Quality Index (PSQI) scores were collected from the medical records. Data analysis was performed using R language programming software. RESULTS: There were 60 patients with AE (age 26.0 [19.8-37.5] years, male 55%) and 66 healthy control subjects (age 30.0 [25.8-32.0] years, male 53%) included in this study. Compared with healthy subjects, patients with AE had higher PSQI scores (7.00 [6.00-8.00] vs 3.00 [2.00-4.00], p < 0.001), lower sleep efficiency (SE 80% [71%-87%] vs 92% [84%-95%], p < 0.001), lower percentage of high-frequency coupling (25% [14%-43%] vs 45% [38%-53%], p < 0.001), higher percentage of REM sleep (19% ± 9% vs 15% ± 7%, p < 0.001), higher percentage of wakefulness (W% 16% [11%-25%] vs 8% [5%-16%], p = 0.074), higher low-frequency to high-frequency ratio (LF/HF 1.29 [0.82-2.40] vs 0.91 [0.67-1.29], p = 0.001), and a higher CPC-derived respiratory disturbance index (9.78 [0.50-22.2] vs 2.95 [0.40-6.53], p < 0.001). Follow-up evaluation of 14 patients showed a decrease in the PSQI score (8.00 [6.00-9.00] vs 6.00 [5.00-7.00], p = 0.008), an increased SE (79% [69%-86%] vs 89% [76%-91%], p = 0.030), and a decreased W% (20% [11%-30%] vs 11% [8%-24], p = 0.035). Multiple linear regression indicated that SE (-7.49 [-9.77 to -5.21], p < 0.001) and LF/HF ratio (0.37 [0.13-0.6], p = 0.004) were independent factors affecting PSQI scores in patients with AE. DISCUSSION: Sleep disorders with autonomic dysfunction are common in patients with AE. Improvements in the PSQI score and SE precede the restoration of sleep microstructural disruption in the remission stage. CPC parameters may be useful in predicting sleep disorders in patients with AE.

[The diagnostic challenge of autoimmune encephalitis]. / Le défi diagnostique des encéphalites auto-immunes.

Autoimmune encephalitis encompasses a spectrum of neurological disorders characterized by an autoimmune response directed against neurons and glia. Around two-thirds of cases exhibit autoantibodies targeting neuronal or glial antigens in the cerebrospinal fluid and/or serum. The diagnosis is based on specific criteria combining a subacute clinical presentation and complementary test results. However, approximately one-quarter of patients do not present any paraclinical abnormalities, making the diagnosis complex. Testing for anti-antibodies is pivotal for diagnosis, and their interpretation should be contextual. Best practices for anti-neural antibody detection involve appropriate sample collection and confirmation of positive results in relation to the clinical picture.

L'encéphalite auto-immune comprend un spectre de troubles neurologiques caractérisés par une réponse auto-immunitaire dirigée contre les neurones et les cellules gliales. Environ deux tiers des cas présentent des autoanticorps dirigés contre des antigènes neuronaux et gliaux dans le liquide céphalorachidien et/ou le sérum. Le diagnostic repose sur des critères spécifiques combinant une présentation clinique subaiguë et des résultats d'examens complémentaires. Environ un quart des patients ne présente pas d'anomalie paraclinique, rendant le diagnostic complexe. La recherche des autoanticorps est cruciale pour le diagnostic de certitude et son interprétation doit être contextuelle. Les bonnes pratiques pour leur dosage impliquent le prélèvement d'échantillons appropriés et la confirmation des résultats positifs par rapport au tableau clinique.

Predictors and Clinical Characteristics of Relapses in LGI1-Antibody Encephalitis.

BACKGROUND AND OBJECTIVES: Relapses occur in 15%-25% of patients with leucine-rich glioma-inactivated 1 antibody (LGI1-Ab) autoimmune encephalitis and may cause additional disability. In this study, we clinically characterized the relapses and identified factors predicting their occurrence. METHODS: This is a retrospective chart review of patients with LGI1-Ab encephalitis diagnosed at our center between 2005 and 2022. Relapse was defined as worsening of previous or appearance of new symptoms after at least 3 months of clinical stabilization. RESULTS: Among 210 patients, 30 (14%) experienced a total of 33 relapses. The median time to first relapse was 23.9 months (range: 4.9-110.1, interquartile range [IQR]: 17.8). The CSF was inflammatory in 11/25 (44%) relapses, while LGI1-Abs were found in the serum in 16/24 (67%) and in the CSF in 12/26 (46%); brain MRI was abnormal in 16/26 (62%) relapses. Compared with the initial episode, relapses manifested less frequently with 3 or more symptoms (4/30 patients, 13% vs 28/30, 93%; p < 0.001) and had lower maximal modified Rankin scale (mRS) score (median 3, range: 2-5, IQR: 1 vs 3, range: 2-5, IQR: 0; p = 0.001). The median mRS at last follow-up after relapse (2, range: 0-4, IQR: 2) was significantly higher than after the initial episode (1, range: 0-4, IQR: 1; p = 0.005). Relapsing patients did not differ in their initial clinical and diagnostic features from 85 patients without relapse. Nevertheless, residual cognitive dysfunction after the initial episode (hazard ratio:13.8, 95% confidence interval [1.5; 129.5]; p = 0.022) and no administration of corticosteroids at the initial episode (hazard ratio: 4.8, 95% confidence interval [1.1; 21.1]; p = 0.036) were significantly associated with an increased risk of relapse. DISCUSSION: Relapses may occur years after the initial encephalitis episode and are usually milder but cause additional disability. Corticosteroid treatment reduces the risk of future relapses, while patients with residual cognitive dysfunction after the initial episode have an increased relapse risk.

Study on clinical features and factors related to long-term outcomes of antibody-negative autoimmune encephalitis.

OBJECTIVE: To delineate the clinical characteristics of antibody-negative autoimmune encephalitis (AE) and to investigate factors associated with long-term outcomes among antibody-negative AE. METHODS: Patients diagnosed with antibody-negative AE were recruited from January 2016 to December 2022 at the Second Xiangya Hospital of Central South University. The study assessed the long-term outcomes of antibody-negative AE using the modified Rankin scale (mRS) and the Clinical Assessment Scale in Autoimmune Encephalitis (CASE). Predictors influencing long-term outcomes were subsequently analyzed. External validation of RAPID scores (refractory status epilepticus [RSE], age of onset ≥60 years, ANPRA [antibody-negative probable autoimmune encephalitis], infratentorial involvement, and delay of immunotherapy ≥1 month) was performed. RESULTS: In total, 100 (47 females and 53 males) antibody-negative AE patients were enrolled in this study, with approximately 49 (49%) experiencing unfavorable long-term outcomes (mRS scores ≥3). Antibody-negative AE was subcategorized into ANPRA, autoimmune limbic encephalitis (LE), and acute disseminated encephalomyelitis (ADEM). Psychiatric symptoms were prevalent in LE and ANPRA subtypes, while weakness and gait instability/dystonia were predominant in the ADEM subtype. Higher peak CASE scores (odds ratio [OR] 1.846, 95% confidence interval [CI]: 1.163-2.930, p = 0.009) and initiating immunotherapy within 30 days (OR 0.210, 95% CI: 0.046-0.948, p = 0.042) were correlated with long-term outcomes. Receiver operating characteristic (ROC) analysis returned that the RAPID scores cutoff of 1.5 best discriminated the group with poor long-term outcomes (sensitivity 85.7%, specificity 56.9%). INTERPRETATION: The ANPRA subtype exhibited poorer long-term outcomes compared to LE and ADEM subtypes, and early immunotherapy was crucial for improving long-term outcomes in antibody-negative AE. The use of RAPID scoring could aid in guiding clinical decision making.

NORSE seasonality may vary geographically in adults.

The mechanisms causing new onset refractory status epilepticus (NORSE) are often unknown. Recently, a seasonal variation with NORSE peaking during the summer was described in a mixed cohort of adults and children why we here studied the seasonal variation in a Danish status epilepticus (SE) cohort. This retrospective cohort study comprised SE patients aged ≥18 diagnosed and treated 2008-2017 at the Odense University Hospital. Clinical characteristics and seasonality of patients fulfilling the diagnostic criteria for NORSE were compared with patients with refractory SE (RSE) due to other reasons and with the seasonal variation of autoantibodies associated with autoimmune encephalitis in the Danish autoimmune encephalitis register. In this cohort, 26 patients met NORSE criteria. As compared to RSE patients not fulfilling NORSE criteria (n = 152), NORSE patients were more likely to have symptoms of systemic inflammation (C-reactive protein concentrations ≥10 mg/L or fever ≥38°C) at admission; nine fulfilled the criteria for febrile infection related epilepsy syndrome (FIRES). In contrast to the even seasonal distribution of patients with RSE not fulfilling the NORSE criteria, admissions due to NORSE peaked during the winter (46.1%, p = 0.04 as compared to non-NORSE RSE); six out of nine FIRES episodes occurred in the winter season. The seasonal variation was not explained by a seasonal variation of the detection rates of autoantibodies associated with autoimmune encephalitis (incl. NMDAR, LGI1, CASPR2, GABAR, GFAP) in a Danish nationwide register (n = 259). In conclusion, we confirm the seasonality of NORSE in a Danish cohort, however, with a peak during winter suggesting a geographical variation not solely explained by autoimmune encephalitis associated with known autoantibodies. PLAIN LANGUAGE SUMMARY: The study investigated the seasonal patterns of new-onset refractory status epilepticus (NORSE), i.e. severe seizures that occur without an obvious cause and require very intensive treatment. In contrast to the previously observed peak frequency in summer, this Danish study found that NORSE cases peak in winter. Furthermore, the seasonal variation in NORSE cases was not found to be associated with autoimmune encephalitis caused by known autoantibodies. Together with the high rate of patients showing symptoms of systemic inflammation compared to other status epilepticus patients, the data suggest a link between misdirected immune system responses and NORSE. The study can therefore help in the further search for the currently unknown causes of NORSE.

[Clinical characteristics of seizure-predominant autoimmune encephalitis and utility of anti-neuronal antibody scores for early treatment].

We analyzed 20 patients diagnosed with autoimmune neurological diseases with seizure predominance. In these patients, we examined the usefulness of Antibody Prevalence in Epilepsy and Encephalopathy (APE2) score and Antibodies Contributing to Focal Epilepsy Signs and Symptoms (ACES) score in autoimmune encephalitis (AE) for facilitating early treatment. APE2 score was positive in 19 of 20 patients. ACES score was positive in 15 of 20 patients, and 4 of 5 of the patients with negative ACES score did not have AE. Comprehensive assessment including the use of the above scores is desirable in the early stage of AE.

Autoimmune and paraneoplastic seizures.

Seizures are a common feature of autoimmune encephalitis and are especially prevalent in patients with the commonest autoantibodies, against LGI1, CASPR2 and the NMDA, GABAB, and GABAA receptors. In this chapter, we discuss the classification, clinical, investigation, and treatment aspects of patients with these, and other autoantibody-mediated and -associated, illnesses. We highlight distinctive and common seizure semiologies which, often alongside other features we outline, can help the clinical diagnosis of an autoantibody-associated syndrome. Next, we classify these syndromes by either focusing on whether they represent underlying causative autoantibodies or T-cell-mediated syndromes and on the distinction between acute symptomatic seizures and a more enduring tendency to autoimmune-associated epilepsy, a practical and valuable distinction for both patients and clinicians which relates to the pathogenesis. We emphasize the more effective immunotherapy response in patients with causative autoantibodies, and discuss the emerging evidence for various first-, second-, and third-line immunotherapies. Finally, we highlight available clinical rating scales which can guide autoantibody testing and immunotherapy in patients with seizures of unknown etiology. Throughout, we relate the clinical and therapeutic observations to the immunobiology and neuroscience which drive these seizures.