Two cases of DYNC1H1 mutations with intractable epilepsy.

Background: The DYNC1H1 gene encodes the heavy chain of cytoplasmic dynein 1, a core structure of the cytoplasmic dynein complex. Dominant DYNC1H1 mutations are implicated in Charcot-Marie-Tooth disease, axonal, type 20, spinal muscular atrophy, lower extremity-predominant 1, and autosomal dominant mental retardation 13 with neuronal migration defects. We report two patients with DYNC1H1 mutations who had intractable epilepsy and intellectual disability (ID), one with and one without pachygyria.

Surgical strategy for refractory epilepsy secondary to porencephaly: ictal SPECT may obviate the need for intracranial electroencephalography. Patient series.

Background: Surgical treatment of intractable epilepsy caused by porencephaly can be difficult because of poorly localizing or lateralizing electroclinical findings. The authors aimed to determine whether noninvasive evaluations are sufficient in these patients.

Observations: Eleven patients were included in this study.

Mitochondrial complex I abnormalities is associated with tau and clinical symptoms in mild Alzheimer's disease.

Background: Mitochondrial electron transport chain abnormalities have been reported in postmortem pathological specimens of Alzheimer's disease (AD). However, it remains unclear how amyloid and tau are associated with mitochondrial dysfunction in vivo. The purpose of this study is to assess the local relationships between mitochondrial dysfunction and AD pathophysiology in mild AD using the novel mitochondrial complex I PET imaging agent [F]BCPP-EF.

TuberOus SClerosis registry to increAse disease awareness (TOSCA) Post-Authorisation Safety Study of Everolimus in Patients With Tuberous Sclerosis Complex.

This non-interventional post-authorisation safety study (PASS) assessed the long-term safety of everolimus in patients with tuberous sclerosis complex (TSC) who participated in the TuberOus SClerosis registry to increase disease Awareness (TOSCA) clinical study and received everolimus for the licensed indications in the European Union. The rate of adverse events (AEs), AEs that led to dose adjustments or treatment discontinuation, AEs of potential clinical interest, treatment-related AEs (TRAEs), serious AEs (SAEs), and deaths were documented. One hundred seventy-nine patients were included in the first 5 years of observation; 118 of 179 patients had an AE of any grade, with the most common AEs being stomatitis (7.

De novo ATP1A3 variants cause polymicrogyria.

Polymicrogyria is a common malformation of cortical development whose etiology remains elusive. We conducted whole-exome sequencing for 124 patients with polymicrogyria and identified de novo variants in eight patients. Mutated causes functional brain diseases, including alternating hemiplegia of childhood (AHC), rapid-onset dystonia parkinsonism (RDP), and cerebellar ataxia, areflexia, pes cavus, optic nerve atrophy, and sensorineural deafness (CAPOS).

Monoallelic and bi-allelic variants in NCDN cause neurodevelopmental delay, intellectual disability, and epilepsy.

Neurochondrin (NCDN) is a cytoplasmatic neural protein of importance for neural growth, glutamate receptor (mGluR) signaling, and synaptic plasticity. Conditional loss of Ncdn in mice neural tissue causes depressive-like behaviors, impaired spatial learning, and epileptic seizures. We report on NCDN missense variants in six affected individuals with variable degrees of developmental delay, intellectual disability (ID), and seizures.

Semiological differences of focal onset bilateral motor (convulsive) seizure between mesial temporal lobe epilepsy and neocortical epilepsy.

Objective: We investigated the semiology of focal onset bilateral motor (convulsive) seizure (FBMS) in patients with intractable focal epilepsy who underwent epilepsy surgery to understand its value in localizing the origin of the seizure.

Methods: The study included 20 patients who underwent resective surgery after intracranial video-EEG monitoring (iEEG) with a favorable seizure outcome (Engel class I), and had at least one FBMS during iEEG. The diagnosis was mesial temporal lobe epilepsy (MTLE) for 7 patients and neocortical epilepsy (NE) for 13 patients (lateral temporal lobe, 3; posterior cortex, 6; frontal lobe, 3; perirolandic, 1).

Limbic encephalitis in a patient with systemic lupus erythematosus successfully treated with high-dose glucocorticoids and intravenous cyclophosphamide therapy: the potential pathogenicity of anti-glutamate receptor antibodies.

Limbic encephalitis (LE) is a clinically defined syndrome characterised by an acute or subacute impairment of short-term memory, seizures and psychiatric symptoms (i.e. depression, anxiety and hallucination).

Clinical manifestations and epilepsy treatment in Japanese patients with pathogenic CDKL5 variants.

Objective: Patients with pathogenic cyclin-dependent kinase-like-5 gene (CDKL5) variants are designated CDKL5 deficiency disorder (CDD). This study aimed to delineate the clinical characteristics of Japanese patients with CDD and elucidate possible appropriate treatments.

Methods: We recruited patients with pathogenic or likely pathogenic CDKL5 variants from a cohort of approximately 1,100 Japanese patients with developmental and epileptic encephalopathies, who underwent genetic analysis.

Long-term safety and effectiveness of stiripentol in patients with Dravet syndrome: Interim report of a post-marketing surveillance study in Japan.

Background: A post-marketing surveillance study is investigating the safety and effectiveness of stiripentol during real-world clinical use in Japanese patients with Dravet syndrome (DS).

Methods: The safety and effectiveness of stiripentol were prospectively investigated over 104 weeks in all patients with DS who were administered the drug from November 2012 through July 2019 in Japan. Patients administered stiripentol for the first time after its approval were defined as "new patients," and those who continued to take the drug after participating in domestic clinical studies were defined as "continuous-use patients.

Exploratory investigation on antibodies to GluN1 and cognitive dysfunction in patients with chronic autoimmune psychosis.

Introduction: Mild cognitive dysfunction has been implicated in a number of psychiatric diseases and affects social functioning. Although clinical criteria were recently proposed for autoimmune psychosis (AP), biomarkers have not yet been established for the severity and prognosis of cognitive dysfunction. We herein investigated the relationships between 3 types of serum antibodies and cognitive dysfunction in chronic psychiatric patients suspected of AP.

[GABA receptor autoimmune encephalitis presenting as transient epileptic amnesia].

This case was a 50-year-old healthy woman. After repeated transient amnesia, she developed tonic-clonic seizures and was admitted to our hospital. The brain MRI showed FLAIR hyperintensities in the left temporal lobe and EEG showed an epileptic discharge starting from the left temporal region.

An exploratory investigation of antibodies to NMDA-type glutamate receptor subunits in serum and cerebrospinal fluid among psychiatric patients with anti-thyroid antibodies.

Introduction: Hashimoto's thyroiditis, which is characterized by anti-thyroid antibodies such as the anti-thyroglobulin (Tg) antibody and anti-thyroid peroxidase (TPO) antibody, is one of the autoimmune diseases associated with psychiatric illnesses. We previously reported a high prevalence of antibodies to N-terminals of N-methyl-D-aspartate (NMDA) type glutamate receptor (GluR) subunits (GluN1-NT and GluN2B-NT2) among psychiatric patients with anti-thyroid antibodies. However, it remains unclear whether the presence of anti-thyroid antibodies influences antibodies to GluN1-NT or GluN2B-NT2 among psychiatric patients.

Pharmacokinetics, tolerability, and clinical effectiveness of perampanel in Japanese patients with epilepsy.

Objective: We aimed to evaluate the influence of concomitant antiepileptic drugs (AEDs) on serum perampanel concentration and to correlate the concentration with clinical response and tolerability.

Methods: A total of 4224 serum samples were obtained from 763 pediatric, adolescent, and adult patients for routine therapeutic drug monitoring. We compared the extent of enzyme induction between cytochrome P450 3A4 (CYP3A4) inducer regimens and built a statistical model to estimate the serum perampanel concentration that considered use of CYP3A4 inducers and inhibitors.

Characteristics of internalization of NMDA-type GluRs with antibodies to GluN1 and GluN2B.

To characterize internalization of NMDA-type glutamate receptors (GluRs) by antibodies to NMDA-type GluRs, we produced rabbit antibodies to N-terminals of human GluN1 and GluN2B, and examined internalization of NMDA-type GluRs in HEK293T cells using confocal microscopy. Internalization of NMDA-type GluRs occurred from at least 10 min after incubation with antibodies to GluN1 and or GluN2B and was temperature-dependent. These findings confirm that antibodies to N-terminals of GluN1 and GluN2B present in the cerebrospinal fluid of patients with NMDAR encephalitis can mediate prompt internalization of NMDA-type GluR complexes.

Impact of CYP2D6, CYP3A5, and ABCB1 Polymorphisms on Plasma Concentrations of Donepezil and Its Metabolite in Patients With Alzheimer Disease.

Background: Donepezil is one of the most commonly prescribed drugs for the treatment of Alzheimer disease. It is predominantly metabolized through CYP2D6 and to a lesser extent by CYP3A4/5. There are conflicting reports regarding the influence of CYP2D6, CYP3A5, and ABCB1 polymorphisms on the plasma concentration of donepezil.

Renal Manifestations of Tuberous Sclerosis Complex: Key Findings From the Final Analysis of the TOSCA Study Focussing Mainly on Renal Angiomyolipomas.

Renal angiomyolipomas are one of the most common renal manifestations in patients with tuberous sclerosis complex (TSC), with potentially life-threatening complications and a poor prognosis. Despite the considerable progress in understanding TSC-associated renal angiomyolipomas, there are no large scale real-world data. The aim of our present study was to describe in detail the prevalence and outcome of renal angiomyolipomas in patients with TSC, enrolled into the TuberOus SClerosis registry to increase disease Awareness (TOSCA) from 170 sites across 31 countries worldwide.

Retained absolute pitch after selective amygdalohippocampectomy.

This study assessed the pre-operative chronic condition and effect of epilepsy surgery in a 21-year-old Japanese woman with drug-resistant right temporal lobe epilepsy (TLE). For this patient, it was crucially important to preserve language and her music capabilities, including absolute pitch (AP), which is found in the general population at less than 0.1%.

Burden of Illness and Quality of Life in Tuberous Sclerosis Complex: Findings From the TOSCA Study.

Research on tuberous sclerosis complex (TSC) to date has focused mainly on the physical manifestations of the disease. In contrast, the psychosocial impact of TSC has received far less attention. The aim of this study was therefore to examine the impact of TSC on health, quality of life (QoL), and psychosocial well-being of individuals with TSC and their families.

Pyridoxal in the Cerebrospinal Fluid May Be a Better Indicator of Vitamin B6-dependent Epilepsy Than Pyridoxal 5'-Phosphate.

Background: We aimed to demonstrate the biochemical characteristics of vitamin B6-dependent epilepsy, with a particular focus on pyridoxal 5'-phosphate and pyridoxal in the cerebrospinal fluid.

Methods: Using our laboratory database, we identified patients with vitamin B6-dependent epilepsy and extracted their data on the concentrations of pyridoxal 5'-phosphate, pyridoxal, pipecolic acid, α-aminoadipic semialdehyde, and monoamine neurotransmitters. We compared the biochemical characteristics of these patients with those of other epilepsy patients with low pyridoxal 5'-phosphate concentrations.

Therapeutic Monitoring of Lacosamide in Japanese Patients With Epilepsy: Clinical Response, Tolerability, and Optimal Therapeutic Range.

Background: Lacosamide is a novel anticonvulsant that acts by enhancing sodium channel slow inactivation. The aims of this study were to evaluate the influence of concomitant antiepileptic drugs (AEDs) on serum lacosamide concentration and explore the relationship between lacosamide serum concentration and both clinical response and adverse effects.

Methods: The authors analyzed 649 serum samples from 426 Japanese patients with epilepsy.