Seizure semiology of anti‐LGI1 antibody encephalitis

Limbic encephalitis associated with anti‐LGI1 antibody (LGI1 encephalitis) presents with a variety of features, the most prominent of which include seizures and progressive disturbance of memory and behaviour. Although varied in semiology, recognition of the pattern of seizures in LGI1 encephalitis is important, as early diagnosis and definitive treatment may prevent subsequent development of cognitive impairment. We present a patient with LGI1 encephalitis and “faciobrachial dystonic seizures‐plus”, which began as classic faciobrachial dystonic seizures and progressed to focal seizures with impaired awareness, dacrystic/gelastic‐like outbursts, ictal speech, manual automatisms, and autonomic signs (tachycardia). Recognition of the broad range of seizure types associated with LGI1 encephalitis is crucial for early diagnosis and definitive treatment. [Published with video sequence on www.epilepticdisorders.com ]     

Three cases of antibody-LGI1 limbic encephalitis and review of literature

Purpose: Antibody-LGI1 limbic encephalitis (LGI1-Ab LE) is an anti-neuronal surface antigen-related autoimmune encephalitis. we report three cases of LGI1-Ab LE, describe the characteristics of clinical manifestation, course of evolution, imaging manifestation and treatment outcomes.

Methods: Data from patients diagnosed with LGI1-Ab LE in the Second Hospital, Hebei Medical University, from June 2016 to July 2017, were retrospectively collected and analyzed. We followed up the patients for 90 days.

Results: Two of the three patients were females, the average age of onset is 53 years old. Epilepsy is the most common clinical manifestations, and one of patients developed faciobrachial dystonic seizures (FBDS), which was recently described as a characteristic feature of LGI1-Ab LE. All patients had cognitive impairment in different degrees and abnormal signal of hippocampus in cranial MRI. All serum LGI1 antibodies were positive, whereas one LGI1 antibodies of CSF were negative. All patients accepted first-line immune therapy and had a good outcome.

Conclusion: LGI1-Ab LE, which is an autoimmune disease, is rare clinically and mostly nonparaneoplastic. We suggest that LGI1-Ab LE be considered in any patient with acute or subacute onset, cognitive dysfunction , various types of seizures, accompanied by mental disorders and hyponatremia, MR showed the involvement of the limbic system. It is necessary to have LE-related antibodies tested. Early immunotherapy can significantly improve the patient's overall prognosis. At the same time, we should also pay attention to the possibility of potential tumors.     

富亮氨酸胶质瘤失活1蛋白抗体阳性边缘叶脑炎临床分析

目的分析富亮氨酸胶质瘤失活1蛋白(leucine-rich glioma inactivated 1,LGi1)抗体相关边缘性脑炎(Limbic encephalitis,LE)的临床特点、诊断及治疗。方法回顾性分析7例LGi1抗体相关LE患者的临床资料、实验室和电生理、影像学检查结果及治疗和预后。结果 7例患者发病年龄22~72岁,男女比例5∶2,7例患者均有精神行为异常、认知功能下降的临床表现。6例患者有癫痫发作,4例出现面臂肌张力障碍(FBDS)。3例脑电图出现慢波或癫痫样波。3例患者MRI检查可见颞叶海马异常信号影。5例患者有低钠血症。6例患者脑脊液氯化物低。所有患者血清LGi1抗体阳性,6例患者脑脊液LGi1抗体阳性。5例合并其他血清自身抗体,所有患者均未发现肿瘤,所有患者经免疫治疗均有效。结论 LGi1抗体相关LE以认知功能障碍、精神行为异常、癫痫发作为主要临床表现,常伴有低钠血症,很少合并肿瘤,头部MRI以颞叶、海马受累为主,免疫治疗有效。     

A case of pediatric anti-leucine-rich glioma inactivated 1 encephalitis with faciobrachial dystonic seizure

BackgroundAnti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis is a rare type of autoimmune encephalitis. A characteristic faciobrachial dystonic seizure (FBDS) is also frequently associated with this disease. Although primarily reported in the adult population, reports of its occurrence in the pediatric population are rare. Here, we describe a case of a 6-year-old girl diagnosed with anti-LGI1 encephalitis that presented with cognitive decline and FBDS.Case presentationThe girl was referred to a pediatric neurology department for uncontrolled seizures and dyskinesia. She initially presented with a memory deficit, abnormal movement of the limbs and trunk, and ataxia. Her cerebrospinal fluid exam was unremarkable, but her brain MRI showed focal T2 high signal intensity in the left anterior putamen and right caudate nucleus. In addition, there were refractory episodes of brief tonic or dystonic movement of the face and arms that were suggestive of FBDS. She was initially treated with intravenous methylprednisolone and phenobarbital, then given another pulse of methylprednisolone and intravenous immunoglobulin as her symptoms persisted. Tests for neuronal autoantibodies revealed the presence of anti-LGI1 antibodies. Subsequent human leukocyte antigen (HLA) typing resulted in the identification of HLA-DRB1 DR7(*07:01 g) DR9(*09:01 g). Screening for thymoma and other neoplasms showed no signs of a tumor. She was treated with rituximab, tocilizumab, and antiseizure medications, including oxcarbazepine, valproic acid, and lamotrigine. Her FBDS and cognitive symptoms showed substantial improvements.ConclusionWhile it is known that anti-LGI1 encephalitis responds well to immunotherapy, our patient showed an incomplete response, requiring further therapy. This is the first report of a pediatric patient with anti-LGI1 encephalitis treated with tocilizumab.     

Adult‐onset drug‐refractory seizure disorder associated with anti–voltage‐gated potassium‐channel antibody

Voltage‐gated potassium channels are widely expressed throughout the entire nervous system. These channels play a critical role in establishing the resting membrane potential and generation of neuronal action potentials. There is mounting evidence that autoantibodies reactive to neuronal cell surface antigens, such as voltage‐gated potassium channels, play a pathogenic role in a wide spectrum of central and peripheral nervous system disorders. We report a case of new‐onset drug‐refractory seizure disorder associated with the presence of high levels of serum anti–voltage‐gated potassium channel antibodies that responded only to immunotherapy. As demonstrated by this case report, anti–voltage‐gated potassium channel antibody associated drug‐refractory seizure disorder, although rare, should be considered in patients with unexplained adult‐onset seizure activity. Once the diagnosis has been established the initiation of immunotherapy should be undertaken without delay.     

Subclinical temporal EEG seizure pattern in LGI1‐antibody–mediated encephalitis

Leucine‐rich glioma inactived‐1 (LGI1) antibodies are associated with limbic encephalitis and distinctive seizure types, which are typically immunotherapy‐responsive. Although nonspecific electroencephalography (EEG) abnormalities are commonly seen, specific EEG characteristics are not currently understood to be useful for suspecting the clinical diagnosis. Based on initial observations in two patients, we analyzed the clinical features and EEG recordings in a larger series of patients (n = 9) and describe a novel ictal pattern that can suggest the diagnosis of LGI1‐antibody–mediated encephalitis, even in the absence of typical clinical features. As expected, psychiatric and cognitive symptoms were common, as were tonic seizures associated with EEG electrodecremental events (often with the so‐called faciobrachial dystonic semiology). Remarkably, in five patients, a near absence of interictal epileptiform discharges contrasted with frequent subclinical temporal lobe seizures, at times triggered by hyperventilation. This latter EEG pattern may facilitate early diagnosis of this serious but potentially treatable condition.     

EEG‐confirmed epileptic activity in a cat with VGKC‐complex/LGI1 antibody‐associated limbic encephalitis

A 5‐year‐old, female client‐owned cat presented with acute onset of focal epileptic seizures with orofacial twitching and behavioural changes. Magnetic resonance imaging showed bilateral temporal lobe hyperintensities and the EEG was consistent with ictal epileptic seizure activity. After antiepileptic and additional corticosteroid treatment, the cat recovered and by 10 months of follow‐up was seizure‐free without any problem. Retrospectively, antibodies to LGI1, a component of the voltage‐gated potassium channel‐complex, were identified. Feline focal seizures with orofacial involvement have been increasingly recognised in client‐owned cats, and autoimmune limbic encephalitis was recently suggested as a possible aetiology. This is the first report of EEG, MRI and long‐term follow‐up of this condition in cats which is similar to human limbic encephalitis.     

Guillain‐Barré syndrome associated with CASPR2 antibodies: two paediatric cases

The pathogenesis of Guillain‐Barré syndrome (GBS) is considered to be, at least in part, mediated by autoantibodies directed against neuronal antigens. Antibodies to contactin‐associated protein‐like 2 (CASPR2), part of the voltage‐gated potassium channel complex (VGKC‐complex), are associated with neurological disease predominantly affecting the peripheral nervous system but are not known to be associated with GBS. We report two cases of ganglioside antibody‐negative paediatric GBS associated with CASPR2 antibodies. Both patients made a complete clinical recovery. The tissue distribution and function of CASPR2 make it a biologically plausible autoimmune target in GBS and its clinical relevance in GBS should be determined in further studies.     

Myoclonic status epilepticus as a presentation of caspr2 antibody‐associated autoimmune encephalitis

We present a case of autoimmune encephalitis associated with antibodies targeting contactin‐associated protein‐like 2. This case is notable because of the presentation with myoclonic status epilepticus and the prolonged clinical course of refractory seizures, which are demonstrated in the accompanying videos, and not previously associated with this condition. Treatment with prednisone, intravenous immunoglobulin, plasma exchange, rituximab, cyclophosphamide, and mycophenolate mofetil resulted in significant functional improvement. Historically, myoclonic status epilepticus is associated with a grave prognosis and minimal chance of meaningful recovery. This case demonstrates that autoimmune encephalitis remains an important differential diagnosis in patients with such a presentation, and that early recognition and the appropriate institution of immunotherapy can result in seizure control and functional recovery. [Published with video sequences]     

Human limbic encephalitis serum enhances hippocampal mossy fiber-CA3 pyramidal cell synaptic transmission

Purpose: Limbic encephalitis (LE) is a central nervous system (CNS) disease characterized by subacute onset of memory loss and epileptic seizures. A well‐recognized form of LE is associated with voltage‐gated potassium channel complex antibodies (VGKC‐Abs) in the patients’ sera. We aimed to test the hypothesis that purified immunoglobulin G (IgG) from a VGKC‐Ab LE serum would excite hippocampal CA3 pyramidal cells by reducing VGKC function at mossy‐fiber (MF)‐CA3 pyramidal cell synapses. Methods: We compared the effects of LE and healthy control IgG by whole‐cell patch‐clamp and extracellular recordings from CA3 pyramidal cells of rat hippocampal acute slices. Results: We found that the LE IgG induced epileptiform activity at a population level, since synaptic stimulation elicited multiple population spikes extracellularly recorded in the CA3 area. Moreover, the LE IgG increased the rate of tonic firing and strengthened the MF‐evoked synaptic responses. The synaptic failure of evoked excitatory postsynaptic currents (EPSCs) was significantly lower in the presence of the LE IgG compared to the control IgG. This suggests that the LE IgG increased the release probability on MF‐CA3 pyramidal cell synapses compared to the control IgG. Interestingly, α‐dendrotoxin (120 nm ), a selective Kv1.1, 1.2, and 1.6 subunit antagonist of VGKC, mimicked the LE IgG‐mediated effects. Conclusions: This is the first functional demonstration that LE IgGs reduce VGKC function at CNS synapses and increase cell excitability.     

PET‐positive extralimbic presentation of anti‐glutamic acid decarboxylase antibody‐associated encephalitis

Anti‐glutamic acid decarboxylase (GAD) antibody‐associated autoimmune encephalitis has been reported mostly as limbic encephalitis. Only few cases with extralimbic involvement are reported with limited investigation. Here, we report an extensive investigation with MRI, PET, and pathological examination. A 66‐year‐old Japanese female with a history of hypothyroidism, colon cancer, pheochromocytoma, and thymoma‐associated myasthenia gravis presented with generalised tonic‐clonic seizures. MRI showed multiple hyperintense lesions and PET showed hypermetabolic lesions in the brain. Biopsy showed non‐specific gliosis, microglial proliferation, and perivascular lymphohistiocytic infiltrates. Various neuronal antibodies were negative, except for anti‐GAD antibody. Anti‐GAD antibody‐associated encephalitis is an increasingly recognised CNS disease. Pathophysiology of this encephalitis is unclear. While PET showed hypermetabolic lesions, the biopsy showed non‐specific changes. The treatments may include immunosuppressants, IVIg, and plasma exchange. One should consider to measure this antibody, in addition to others, when autoimmune encephalitis is suspected [Published with video sequences].     

Epilepsia partialis continua in tick‐borne Russian spring‐summer encephalitis

Objectives – Epilepsia partialis continua (EPC) is characterized by localized continuous jerks, from time to time with spreading Jacksonian seizures and, more rarely, secondarily generalized tonic‐clonic seizures. EPC has numerous possible etiologies. In this paper we describe EPC in the tick‐borne Russian spring‐summer encephalitis (TBRSSE) and compare it with Rasmussen syndrome. Methods – We included patients with EPC in TBRSSE (between 2003 and 2010). The diagnosis was verified by immunology (antibodies against TBRSSE virus). The patients were followed 1–7 (mean 3.4) years. Results – We studied 10 patients (eight males, age 10–21 years) with MRI and video‐EEG. Nine developed EPC after acute TBRSSE (meningoencephalitic form), and one had a tick bite without clinical symptoms of encephalitis, but with subsequent EPC. All patients came from Ural and Siberia. The onset was at age 4–14 (mean 8.6 years). The interval from onset of TBRSSE or the tick bite to seizure onset was 1 day–4 years. We identified three phases of clinical course EPC in TBRSSE: (i) acute (meningoencephalitic/encephalitic); (ii) development of EPC; and (iii) chronic EPC. The effect of antiepileptic drugs differed according to seizure types. Conclusion – EPC caused by TBRSSE is relatively frequent in the Eastern parts of the Russian Federation but not west of the Ural. Unlike Rasmussen encephalitis, EPC with TBRSSE does not progress even in the long term. It appears as disabling but not fatal condition with a time course where three phases can be distinguished.     

A 9-year neuropsychological report of a patient with LGI1-associated limbic encephalitis

Introduction: Anti-leucine-rich glioma-inactivated 1 limbic encephalitis (LGI1-LE) is an autoimmune disorder associated with antibodies to voltage-gated potassium channels (VGKC). It is a non-paraneoplastic and partially reversible encephalitis that can be diagnosed via serological testing. Untreated LGI1-LE can be associated with neurocognitive as well as neuropsychiatric sequelae. Here we report the neuropsychological and clinical profile of a patient with LGI1-LE following three different treatment approaches: plasmapheresis (PA), intravenous immunoglobulin (IVIG), and corticosteroids (CO).

Method: We investigated our patient with 10 neuropsychological evaluations obtained over a 9-year follow-up period. Multiple MRI scans, EEG recordings, neurological examinations, and serum tests were also obtained.

Results: The neurocognitive profile of our patient was characterized by long-term memory impairment (verbal and visual-spatial), and deficits in aspects of executive functioning and language. Neuropsychiatric symptoms of depression and anxiety were noted intermittently.

Conclusions: Non-specific treatment prior to diagnosis had marginal effects on neurocognitive profile, neuropsychiatric symptoms, or control of epileptic seizure. In contrast, specific treatments for LGI1-LE following diagnosis resulted in neurocognitive improvement and epileptic control. Among the three treatments, IVIG and CO had the most beneficial impact on neurocognitive status, likely due to the continuity of administration.     

Altered transporter‐mediated neocortical GABA release in Rasmussen encephalitis

To learn whether epileptic seizures in Rasmussen encephalitis (RE) may be promoted by insufficient γ‐aminobutyric acid (GABA) release. ³H‐GABA was released from neocortical synaptosomes through transporter reversal following intrasynaptosomal Na⁺ accumulation by veratridine that prevents inactivation of Na⁺ channels. Tissues of three RE patients were compared with those of nine non‐RE. In RE, the release was markedly reduced. In non‐RE, the extracellular Ca²⁺ concentration ([Ca²⁺]_e) was inversely related to the amount of release. In RE, the percental decline of additional release upon withdrawal was linked with the presurgical duration of epilepsy. Permanent opening of Na⁺ channels by veratridine resembles maximal frequency of action potentials corresponding to epileptic seizures. These are preceded by a fall in [Ca²⁺]_e. Zero [Ca²⁺]_e increased release through the Na⁺/Ca²⁺ exchanger additionally elevating intrasynaptosomal Na⁺. This enhanced GABA release probably reflects an antiseizure mechanism. In RE, the additional release gets lost over epilepsy duration.     

A 13‐year‐old girl with proximal weakness and hypertrophic cardiomyopathy with danon disease

Danon disease is caused by deficiency of lysosome‐associated membrane protein‐2 (LAMP‐2). It is characterized clinically by cardiomyopathy, myopathy, and mental retardation in boys. Herein we report a 13‐year‐old female patient with Danon disease who presented with early‐onset skeletal myopathy and cardiomyopathy. She had a de novo novel mutation in the LAMP2 gene, and her muscles showed many autophagic vacuoles with sarcolemmal features and complete absence of LAMP‐2 expression. To the best of our knowledge, this girl is one of the earliest‐onset manifesting carriers of Danon disease with typical muscle pathology. Muscle Nerve, 2010