Long-term Effect of Multichannel tDCS Protocol in Patients with Central Cortex Epilepsies Associated with Epilepsia Partialis Continua.

Epilepsia partialis continua (EPC) is a rare type of focal motor status epilepticus that causes continuous muscle jerking in a specific part of the body. Experiencing this type of seizure, along with other seizure types, such as focal motor seizures and focal to bilateral tonic-clonic seizures, can result in a disabling situation. Non-invasive brain stimulation methods like transcranial direct current stimulation (tDCS) show promise in reducing seizure frequency (SF) when medications are ineffective. However, research on tDCS for EPC and related seizures is limited. We evaluated personalized multichannel tDCS in drug-resistant EPC of diverse etiologies for long-term clinical efficacy We report three EPC patients undergoing a long-term protocol of multichannel tDCS. The patients received several cycles (11, 9, and 3) of five consecutive days of stimulation at 2 mA for 2 × 20 min, targeting the epileptogenic zone (EZ), including the central motor cortex with cathodal electrodes. The primary measurement was SF changes. In three cases, EPC was due to Rasmussen's Encephalitis (case 1), focal cortical dysplasia (case 2), or remained unknown (case 3). tDCS cycles were administered over 6 to 22 months. The outcomes comprised a reduction of at least 75% in seizure frequency for two patients, and in one case, a complete cessation of severe motor seizures. However, tDCS had no substantial impact on the continuous myoclonus characterizing EPC. No serious side effects were reported. Long-term application of tDCS cycles is well tolerated and can lead to a considerable reduction in disabling seizures in patients with various forms of epilepsy with EPC.

Rasmussen's syndrome treated with anakinra.

BACKGROUND AND OBJECTIVE: Rasmussen's encephalitis (RE) is a rare chronic neurological disorder, characterized by unilateral inflammation of the cerebral cortex, refractory focal epilepsy or epilepsia partialis continua, hemiparesis, and progressive cognitive decline. Interleukin-1 (IL-1) plays an important role in neuroinflammation as a key element in the activation of the inflammatory IL-1ß-IL-1 receptor type 1 (IL-1R1) axis. Anakinra, an IL-1 inhibitor, is successfully used in patients with new onset refractory status epilepticus and febrile infection-related epilepsy syndrome. METHODS AND RESULTS: We present 38-year-old male with RE having right-sided hemiparesis and continuous spasms being unresponsive to immune modulatory therapies like pulse steroid, intravenous immunoglobulin and anti-seizure drugs. After treatment with anakinra for three weeks, the continuous spasms almost completely subsided, and his muscle strength returned to normal. DISCUSSION: Anakinra may be considered as a treatment option in patients with RE and refractory seizures.

Unilateral Autoimmune Encephalitis: A Case Report on a Rare Manifestation of Myelin Oligodendrocyte Glycoprotein Antibody Disease.

Myelin oligodendrocyte glycoprotein (MOG)-associated disease (MOGAD) is a rare, antibody-mediated inflammatory demyelinating disorder of the central nervous system (CNS) that has varying phenotypes. FLAIR (fluid-attenuated inversion recovery)-hyperintense Lesions in Anti-MOG-associated Encephalitis with Seizures (FLAMES) is a much rarer manifestation of cortical encephalitis encountered in MOGAD. We report a rare case of a nine-year-old girl who presented with a drop in her academic performance and right-sided Epilepsia partialis continua. Magnetic resonance imaging (MRI) of the brain detected evidence for unilateral (left) cortical encephalitis with peri-ictal juxtacortical edema. An electroencephalogram revealed a hemi-generalized poly spike and wave discharges in the left hemisphere, several of which correlated with myoclonic jerks. The cerebrospinal fluid (CSF) analysis was normal. Autoimmune workup resulted in a positive serum MOG-immunoglobulin G (IgG), which confirmed the diagnosis of FLAMES. The child showed an excellent clinical response to intravenous methylprednisolone and intravenous immunoglobulins therapy.

Epilepsia partialis continua and unilateral cortical-subcortical FLAIR-hyperintense lesion in Rasmussen's encephalitis: Is it diagnostic?

OBJECTIVE: Rasmussen encephalitis (RE) is a focal encephalitis, characterized by epilepsia partialis continua (EPC) with or without seizures and progressive unilateral deficits. Imaging characteristics of RE have been rarely described in detail in relation to EPC. So, the study aimed to explore if any relationship exists between the imaging characteristics and the presence or evolution of EPC in patients with RE. METHODS: This retrospective study included 11 patients with RE fulfilling the European consensus statement on RE followed between 2015 and 2020. RESULTS: The mean age for onset of seizures was 12 years (range 2.5-24 years). Seven patients had limb EPCs, two had face EPCs, face, and limb EPC in one, and lingual EPC in one patient. The first MRI was done within 1 day to 1 month of the onset of seizures. It was normal in two patients and showed only cortical atrophy, focal or hemispheric in four patients, caudate atrophy in two, and cortical or subcortical hyperintensity (HI) in six patients. Follow-up MRI, within 3 weeks to 6 months of the onset of EPC (mean 1.6 months) showed paramedian frontal HI with limb EPC in six patients. Insular HI in four patients; two had facial EPCs while lingual EPC and limb EPC with facial EPC was observed in one patient each. SIGNIFICANCE: Fluid-attenuated inversion recovery (FLAIR) HI and focal cortical atrophy on MRI is the most common finding in the early course of RE. T2 and FLAIR hyperintensity in the paramedian frontal or insular cortex may antedate the onset of EPC or may occur simultaneously with EPC.

Clinical characterization of non-ketotic hyperglycemia-related seizures: A systematic review and individual participant data meta-analysis.

New-onset epileptic seizures and status epilepticus (SE) are the most frequent neurological manifestations of non-ketotic hyperglycemia (NKH), an acute complication of diabetes mellitus (DM). Treatment consists of the correction of the underlying metabolic disorder, whereas anti-seizure medications (ASMs) may even worsen seizures. Evidence on NKH-related seizures is currently restricted to case reports and small case-series. We conducted a systematic review of the PubMed, Embase, and Cochrane Library databases to provide a comprehensive description of NKH-related seizures. Statistical analyses were performed to explore possible associations of glycemic and osmolarity levels with clinical variables. We selected 130 publications and 332 patients (186 males, mean age: 61.1 years). DM was newly-diagnosed in 40%. Mean glycemia and osmolarity levels at presentation were 529.7 mg/dL and 309.6 mmol/mol, respectively; 22.6% showed other neurological symptoms besides seizures. Focal motor seizures were the prominent seizure type (49.4%); non-motor focal seizures (23.2%) most commonly manifested as visual symptoms. Reflex seizures occurred in 10.5%. Brain MRI in 48.7% of cases showed focal T2 subcortical hypodensity and/or overlying cortical T2 hyperintensity with DWI restriction. ASMs were administered in 54.2% of cases, achieving seizure control in just 18.3%. Higher osmolarity levels were associated with newly-diagnosed DM (p = 0.002) and other symptoms at presentation (p < 0.001). Glycemic values were higher in patients with focal aware seizures with motor onset compared to those with focal seizures without motor onset (p = 0.0046) or focal seizures with impaired awareness (p = 0.0306). Lower glycemic values were associated with reflex seizures (p = 0.036) and ASM administration (p < 0.001). NKH-related seizures should be suspected in adults with new-onset clustering focal seizures arising from the motor or posterior cortices, even in the absence of a history of DM. Typical focal changes on brain MRI, while not pathognomonic, can drive the clinical diagnosis. Statistical associations suggest a key role of hyperglycemia in the excitability of higher-energy-demanding cortical areas.

Epilepsia Partialis continua secondary to diabetic ketoacidosis.

Epilepsia partialis continua is a rare epileptic syndrome presenting with simple, partial, repetitive motor seizures. It can be a result of structural central nervous system lesion or due to metabolic causes. We report a case of a 65-year-old male patient diagnosed with EPC secondary to diabetic ketoacidosis.

Sporadic Creutzfeldt-Jakob Disease With Status Epilepticus: Molecular Mechanisms and a Scoping Review of the Literature.

Creutzfeldt-Jakob disease (CJD) is a rapidly progressing neurodegenerative disorder and is a spongiform encephalopathy. A 59-year-old male presented with subacute-onset worsening encephalopathy and was found to be in non-convulsive status epilepticus (NCSE) requiring intubation and a midazolam infusion for refractory seizures. Electroencephalogram (EEG) revealed triphasic repeats with focal epileptogenic originating from the left parietal region. The patient continued to have up to 25-40 non-convulsive seizures per day. Cerebrospinal fluid (CSF) analysis revealed elevated 14-3-3 and tau protein. A real-time quaking-induced conversion assay in CSF was positive. The patient was diagnosed with probable sporadic CJD based on criteria from the Centers for Disease Control. Supportive treatment was provided. Cellular prion protein (PrPC) plays an important role in myelination of the peripheral nervous system, regulation of the neuronal membrane, and circadian rhythm. The molecular mechanisms of CJD involve the catalyzation of the physiological PrPC into the pathological prion protein (PrPSc). This post-translational change in conformation leads to the generation of PrPSc and is involved in spongiform encephalopathies. Mechanisms of neurodegeneration include astrocytosis, neuronal apoptosis, and amyloid plaque formation. A scoping literature review was conducted in three databases on cases of CJD with SE. A total of 13 cases are identified that include the type of CJD and the morphology of the seizures. NCSE is the most prevalent form of SE in patients with CJD.

Chronic T Cell Encephalitis Responsive to Immunotherapy.

Chronic encephalitis manifesting as an epilepsy syndrome most commonly presents as Rasmussen's syndrome, usually characterized by epilepsia partialis continua, hemiparesis, and progressive cortical deficits such as aphasia, hemianopia, and cognitive decline. It is characterized by progressive hemispheric cortical atrophy on imaging and is usually seen in childhood. Adult-onset of the syndrome is rare, and only a few cases have been reported with bilateral symptoms. We present a patient with pseudobulbar affect and frontal lobe dysfunction who developed multifocal myoclonic jerks, right hemibody focal motor seizures, and right hemiparesis with bilateral cerebellar signs. Magnetic resonance imaging showed progressive hemispheric atrophy and bilateral features in Positron emission tomography-computed tomography (PET CT). Brain biopsy revealed chronic T-cell infiltrate. We discuss this case as the patient had several features that were atypical for Rasmussen's encephalitis (or syndrome).

Role of diagnostic imaging in Rasmussen's encephalitis - A case report from Nepal.

Rasmussen's encephalitis (RE) is a relatively rare chronic inflammatory neurological disease that usually only affects one hemisphere of the brain. It primarily affects children under the age of 10, although it can also affect teens and adults, causing drug-resistant seizures, progressive hemiparesis, and dementia. RE presents as a challenging diagnosis with MRI as the cornerstone of the evaluation and nuclear imaging as a complementary tool. We'd like to present a case of a 12-year-old girl who was diagnosed with RE after an MRI. In this study, we examine the diagnostic criteria, differential diagnoses, and issues that underpin the diagnostic challenge in great detail.

Rituximab in Rasmussen's encephalitis: A single center experience and review of the literature.

Rasmussen's encephalitis (RE) is a rare chronic inflammatory disease of the brain resulting in unilateral hemispheric atrophy with drug-resistant focal epilepsy associated with a variable degree of progressive hemiparesis and cognitive decline. The precise etiology of RE is unknown but presumed to have a neuroinflammatory pathobiological basis. Only surgery halts progression of the disease, but may occur at the expense of a fixed but otherwise inevitable neurological deficit. Therefore, the question of medical management is an important consideration. Reports of rituximab use in patients with RE were presented at the American Epilepsy Society annual meeting in 2008. Good published evidence for its usage has been very slow to emerge since then. However, rituximab continues to be listed in discussions of treatment options for patients with RE, though other monoclonal antibodies have since been used with comparable outcomes. We describe a series of nine patients including two with adult-onset RE. Rituximab was used early in the disease course (range 1-108 months; mean 32 months). Of nine patients with RE, there was significant benefit in their seizure burden with rituxamab. Seizure freedom occurred in 3 patients. Epilepsia partialis continua (EPC) was present in 4/9 and no focal motor deficit noted in 4/9. No progression of a neurological deficit was present in 2/9 and evidence of progression with neuroimaging was terminated with rituxamab in 5/9 supporting early use of rituxamab in patients with RE.

The importance of timing in epilepsia partialis continua.

INTRODUCTION: Timing is one of the most important modifiable prognostic factors in the management of status epilepticus. Epilepsia partialis continua (EPC) is a status epilepticus subtype of highly variable, occasionally prolonged, duration. The aim of this study was to analyse the relationship between EPC duration and outcomes. METHODS: We performed an observational prospective study of all patients with EPC admitted to our tertiary hospital between 1 September 2017 and 1 September 2018. RESULTS: The sample included 10 patients, of whom 9 were women; median age was 74 years. The most frequent aetiology was cerebrovascular disease (n = 6). EPC onset occurred outside the hospital in 5 patients, with a median time to hospital admission of 4 hours. The median time to treatment onset (TT) for all patients was 12.3 hours. The median time from treatment onset to EPC control (TC) was 30 hours; TC showed a strong positive correlation with TT (Spearman's rho = 0.88). Six patients presented hyperglycaemia at onset; this was positively correlated with TC (rho = 0.71). All 6 patients with hyperglycaemia presented a brain injury explaining the EPC episode. CONCLUSIONS: Delays were observed in different phases of EPC management, which was related to longer duration of the episode. Glycaemia was also related to episode duration, probably acting as a triggering factor rather than as the aetiology.

Epilepsia Partialis Continua (EPC) as an Uncommon Initial Presentation of Cerebral Venous Sinus Thrombosis (CVST).

Cerebral venous sinus thrombosis (CVST) is a rare type of cerebrovascular disease that affects mainly young to middle-aged adults. The main clinical presentation of CVST includes progressive headache, focal neurological deficit, disturbance of conscious level, and epileptic seizures, which can occur early or late in the disease process. Generalized seizure has been recognised as the most common seizure subtype among patients with CVST and epileptic seizures. Epilepsia partialis continua (EPC), a subclass of focal motor status epilepticus, has rarely been reported as the initial presenting feature of CVST. Here, an encounter of CVST with an isolated initial presentation of EPC involving the right hand is presented. The initial discordant clinical and radiological findings prompted further investigations that revealed patchy venous infarction along the precentral gyrus that attributed to the occurrence of EPC.

Epilepsia Partialis Continua a Clinical Feature of a Missense Variant in the ADCK3 Gene and Poor Response to Therapy.

INTRODUCTION: Coenzyme Q10 deficiency can be due to mutations in Coenzyme Q10-biosynthesis genes (primary) or genes unrelated to biosynthesis (secondary). Primary Coenzyme Q10 deficiency-4 (COQ10D4), also known as autosomal recessive spinocerebellar ataxia-9 (SCAR9), is an autosomal recessive disorder caused by mutations in the ADCK3 gene. This disorder is characterized by several clinical manifestations such as severe infantile multisystemic illness, encephalomyopathy, isolated myopathy, cerebellar ataxia, or nephrotic syndrome. METHODS: In this study, whole-exome sequencing was performed in order to identify disease-causing variants in an affected girl with developmental regression and Epilepsia Partialis Continua (EPC). Next, Sanger sequencing method was used to confirm the identified variant in the patient and segregation analysis in her parents. CASE PRESENTATION: The proband is an affected 11-year-old girl with persistent seizures, EPC, and developmental regression including motor, cognition, and speech. Seizures were not controlled with various anticonvulsant drugs despite adequate dosing. Progressive cerebellar atrophy, stroke-like cortical involvement, multifocal hyperintense bright objects, and restriction in diffusion-weighted imaging (DWI) were seen in the brain magnetic resonance imaging (MRI). CONCLUSIONS: A novel homozygous missense variant [NM_020247.5: c.814G>T; (p.Gly272Cys)] was identified within the ADCK3 gene, which is the first mutation in this gene in the Iranian population. Bioinformatics analysis showed this variant is damaging. Based on our patient, clinicians should consider genetic testing earlier to instant diagnosis and satisfactory treatment based on exact etiology to prevent further neurologic sequelae.

Rasmussen's encephalitis: Imaging spectrum on simultaneous FDG-PET and MRI imaging correlation.

Rasmussen encephalitis (RE) is a rare, chronic, idiopathic, progressive, inflammatory, neurodegenerative disease process and typically seen in pediatric cohort. Although primarily a disease affecting children, adult cases with RE have also been reported. It manifests as drug refractory epilepsia partialis continua (EPC). Immunomodulation, although delays progression of disease, seldom influences outcome. Imaging is crucial for early diagnosis, and monitoring disease progression. Magnetic resonance imaging (MRI) is mainstay of imaging with nuclear imaging being a complimentary tool for diagnosing RE. Typical imaging features of RE on MRI are hemispherical atrophy, caudate nucleus atrophy, ex vacuo dilatation of the ventricular system and sulci. We review 5 cases of RE who fulfilled diagnostic criteria proposed by Bien et al. in 2005. One patient had typical imaging pattern of RE while other four patients had atypical imaging features of RE on PET-MRI.

Repetitive transcranial magnetic stimulation (rTMS) as therapy in an infant with epilepsia partialis continua.

Introduction: We present a case of a 10-month-old girl undergoing repetitive TMS (rTMS) for the treatment of drug-resistant epilepsy. Case report: A 10-month-old girl, later diagnosed with pathogenic POLG1 mutations, presented to our institution with chronic progressive EPC (epilepsia partialis continua) manifesting as a frequent, left-sided, synchronous continuous jerking of the arms and legs. The seizures were drug-resistant to multiple antiseizure medications and epilepsy surgery, responding only to continuous anesthesia. rTMS therapy was attempted to interrupt seizures. Results: rTMS therapy, using an activating protocol to introduce a temporary lesion effect, was used to interrupt persistent, ongoing seizures. Conclusion: rTMS can be safely used to abort seizures in patients as young as 10 months old.

Epilepsia partialis continua associated with ketotic hyperglycemia and tuberculous meningoencephalitis: A case report.

We report the case of an 18-year-old girl who presented with several episodes of simple partial motor seizures compatible with the diagnosis of epilepsia partialis continua. In addition to ketotic hyperglycemia, tuberculous meningoencephalitis was diagnosed based on clinical, biological, and brain imaging findings. The seizures ceased after normalization of glycemia.

Temporal subcortical T2 hypointensity on MRI in epilepsia partialis continua, a non ketotic hyperglycemia rather than herpes encephalitis.

PURPOSE: Hyperglycemia can present as many neurological problems, one of them is seizure. Different brain MRI features can be seen in focal seizures associated with nonketotic hyperglycemia that subcortical T2 hypointensity is the only characteristic one. Finding this MRI feature is highly valuable in early diagnosis and treatment. METHODS: Our patient was a 60-year-old female, a case of type 2 diabetes mellitus. She was brought to Emergency Room (ER) with focal colonic status epilepticus of right face and arm associated with confusion and drowsiness progressed over 2 weeks prior to admission. At first, acyclovir was started alongside anti-seizure medication with doubt of herpes encephalitis but antiviral was discontinued after normal LP result and characteristic MRI features. RESULTS: Subcortical T2 hypointensity in left temporal and insular lobe was seen on first MRI that was resolved on follow up MRI after she was treated. CONCLUSION: Epilepsia partialis continua in the setting of non ketotic hyperglycemia should be differentiated from that in herpes encephalitis in a diabetic patient presenting with subacute confusional state and focal status epilepticus considering characteristic MRI finding of subcortical T2 hypointensity.

Epilepsia partialis continua associated with the p.Arg403Cys variant of the DNM1L gene: an unusual clinical progression with two episodes of super-refractory status epilepticus with a 13-year remission interval.

Dynamin-1-like (DNM1L) is a gene located on chromosome 12p11.21 that encodes for dynamin-related protein (DRP1), a GTPase involved in mitochondrial and peroxisomal fusion, which plays a pivotal role in brain development. The missense variant, p.Arg403Cys, is clinically associated with childhood-onset super-refractory status epilepticus, with either subsequent poor neurological outcome or death (described in 13 patients). We present a 20-year-old girl carrying this mutation with a history of two episodes of super-refractory focal myoclonic status epilepticus which manifested as epilepsia partialis continua (EPC) with a 13-year interval, during which she displayed moderate intellectual disability, social and school reintegration, without complete control of myoclonic manifestations. The first status, which occurred at the age of six, was associated with transient left side thalamic involvement and the second episode with right side transient basal ganglia hyperintensity on MRI. After the second status, a persistent vegetative state with both drug-resistant epilepsia partialis continua and reticular myoclonus endured; the MRI showed progressive brain atrophy. In contrast to previous published cases, this new case of childhood-onset DNM1L encephalopathy demonstrated biphasic clinical progression. The main features of our patient were EPC, super-refractory status epilepticus, and transient and migrating subcortical thalamic hyperintensity on MRI at onset. The unusual clinical course is also noticeable, indicating possible epigenetic and/or protective factors, without underestimating the progressive and genetic basis of this encephalopathy. Precise characterization of seizures and whole-exome sequencing are crucial in order to establish early diagnosis.

Epilepsia partialis continua in relapsing-remitting multiple sclerosis: A possible distinct relapse phenotype.

Epilepsia partialis continua (EPC) is a rare phenomenon in multiple sclerosis (MS). We describe a patient with relapsing-remitting MS and three episodes of EPC, with refractoriness to anti-seizure drugs but corticosteroid-responsiveness. No lesions likely attributable to her episodes of EPC were seen on 1.5 Tesla MRI, which we hypothesize was due to the small volume of presumed cortical/juxtacortical lesions involving the primary motor cortex. The association with relapsing-remitting disease, corticosteroid responsiveness, and dissemination of episodes of EPC in both space and time in our patient suggest that EPC may represent a distinct relapse phenotype in MS.