Biallelic SHQ1 variants in early infantile hypotonia and paroxysmal dystonia as the leading manifestation.

Biallelic SHQ1 variant-related neurodevelopmental disorder is extremely rare. To date, only six affected individuals, from four families, have been reported. Here, we report eight individuals, from seven unrelated families, who exhibited neurodevelopmental disorder and/or dystonia, received whole-genome sequencing, and had inherited biallelic SHQ1 variants. The median age at disease onset was 3.5 months old. All eight individuals exhibited normal eye contact, profound hypotonia, paroxysmal dystonia, and brisk deep tendon reflexes at the first visit. Varying degrees of autonomic dysfunction were observed. One individual had cerebellar atrophy at the initial neuroimaging study, however, three individuals showed cerebellar atrophy at follow-up. Seven individuals who underwent cerebral spinal fluid analysis all had a low level of homovanillic acid in neurotransmitter metabolites. Four individuals who received 99mTc-TRODAT-1 scan had moderate to severe decreased uptake of dopamine in the striatum. Four novel SHQ1 variants in 16 alleles were identified: 9 alleles (56%) were c.997C > G (p.L333V); 4 (25%) were c.195T > A (p.Y65X); 2 (13%) were c.812T > A (p.V271E); and 1 (6%) was c.146T > C (p.L49S). The four novel SHQ1 variants transfected into human SH-SY5Y neuronal cells resulted in a retardation in neuronal migration, suggestive of SHQ1 variant correlated with neurodevelopmental disorders. During the follow-up period, five individuals still exhibited hypotonia and paroxysmal dystonia; two showed dystonia; and one had hypotonia only. The complex interactions among movement disorders, dopaminergic pathways, and the neuroanatomic circuit needs further study to clarify the roles of the SHQ1 gene and protein in neurodevelopment.

Congenital disorders of glycosylation and infantile epilepsy.

Congenital disorders of glycosylation (CDG) are a group of rare inherited metabolic disorders caused by defects in various defects of protein or lipid glycosylation pathways. The symptoms and signs of CDG usually develop in infancy. Epilepsy is commonly observed in CDG individuals and is often a presenting symptom. These epilepsies can present across the lifespan, share features of refractoriness to antiseizure medications, and are often associated with comorbid developmental delay, psychomotor regression, intellectual disability, and behavioral problems. In this review, we discuss CDG and infantile epilepsy, focusing on an overview of clinical manifestations and electroencephalographic features. Finally, we propose a tiered approach that will permit a clinician to systematically investigate and identify CDG earlier, and furthermore, to provide genetic counseling for the family.

Genotype-Phenotype Dissociation in Two Taiwanese Children with Molybdenum Cofactor Deficiency Caused by MOCS2 Mutation.

BACKGROUND: To describe the genotype-phenotype dissociation in two Taiwanese patients with molybdenum cofactor deficiency (MoCoD) caused by MOCS2 gene mutations. PATIENT DESCRIPTION: Patient 1 exhibited early-onset neurological symptoms soon after birth, followed by subsequent myoclonic seizures and movement disorder. The brain magnetic resonance imaging (MRI) showed diffuse brain injury with cystic encephalomalacia along with bilateral globus pallidi involvement, hypoplasia of corpus callosum, and cerebellar atrophy. Patient 2 had a mild phenotype with prominent movement disorder after intercurrent illness, and the brain MRI showed selective injury of the bilateral globus pallidi and the cerebellum. Both patients had markedly low levels of plasma uric acid and harbored the same MOCS2 homozygous c.16C > T mutation. Patient 1 showed chronic regression of developmental milestones and died of respiratory failure at the age of 8 years, whereas patient 2 demonstrated improvement in motor function. CONCLUSION: Genotype-phenotype dissociation could be noted in patients with MoCoD due to MOCS2 mutation. Patients with neonatal seizures, developmental delay, movement disorder, and motor regression after an illness, as well as focal or bilateral involvement of the globus pallidi on the neuroimages, should undergo biochemical testing of plasma uric acid. A pronounced plasma uric acid level is a good indicator of MoCoD. Early diagnosis can allow early provision of adequate genetic counseling.

Risk of SUDEP during infancy.

Risk of sudden unexpected death in epilepsy (SUDEP) in children is influenced by different factors such as etiology, seizure type and frequency, treatment, and environment. A greater severity of epilepsy, in terms of seizure frequency, seizures type, especially with nocturnal generalized tonic-clonic seizures (GTCS), and resistance to anti-seizure medication are predisposing factors to SUDEP. Potential mechanisms of SUDEP might involve respiratory, cardiovascular, and central autonomic dysfunctions, either combined or in isolation. Patients with epilepsy carrying mutations in cardiac channelopathy genes might be disposed to seizure-induced arrhythmias. Other than in channelopathies, SUDEP has been reported in further patients with genetic epilepsies due to mutations of genes such as DEPDC5, TBC1D24, FHF1, or 5q14.3 deletion. Age-related electro-clinical differences in GTCS may therefore be relevant in explaining differences in SUDEP between adults and children. Typical GTCS represent a rare seizure type in infants and toddlers, they are characterized by a shorter tonic phase and, in direct proportion, by shorter postictal generalized EEG suppression (PGES). The presence of night-time supervision has been found to reduce SUDEP risk, likely reducing SUDEP incidence in children. Reconsideration of safety protocols in epilepsy monitoring units with the aim of reducing the risk of SUDEP, and the use of devices for seizure detection, might contribute to reduce the risk of death in patients affected by epilepsy. This article is part of the Special Issue "Severe Infantile Epilepsies".

Diagnostic yield and treatment impact of whole-genome sequencing in paediatric neurological disorders.

AIM: To investigate the diagnostic yield and treatment impact of whole-genome sequencing (WGS) in patients with paediatric neurological disorders. METHOD: From January 2016 to December 2019, paediatric patients who had suspected genetic neurological disorders were assessed using WGS. The phenotypes of eligible patients were divided into four groups: patients with neurodevelopmental disorders; patients with epilepsy; patients with neuromuscular disorders; and patients with movement disorders. RESULTS: A total of 214 consecutive patients (128 males, 86 females) underwent WGS. The mean (SD) age of disease onset was 13.8 (27.6) months (range 1d-15y 5mo). The mean (SD) age at which WGS was performed was 71.7 (58.9) months (range 8d-18y). A molecular diagnosis was reported in 43.9% of patients. The highest diagnostic rate was achieved in 62.5% of patients with neuromuscular disorders, 47.5% of patients with epilepsy, 41.1% of patients with neurodevelopment disorders, and 15.4% of patients with movement disorders. All 94 patients with a WGS diagnosis were given access to genetic counselling and 23.4% of patients had immediate changes in treatment strategies after undergoing WGS. INTERPRETATION: WGS allows paediatric neurologists to integrate genomic data into their diagnosis and adjust management strategies for a range of clinical and genetically heterogeneous disease entities to improve the clinical outcomes of patients. In our cohort, the diagnosis of a significant proportion of patients was reached through WGS (43.9%). Clinicians could use these results to directly guide the management of their patients and improve their clinical outcomes (23.4%). What this paper adds For selected children in our cohort, the diagnostic yield of whole-genome sequencing (WGS) was 43.9%. WGS can be used to expand our knowledge of phenotype-genotype variations.

Urine catecholamines in children with severe Enterovirus A71 infection: comparison with paediatric septic shock.

Purpose: Hypercatecholaminemia-related heart failure has been proposed as the main cause of enterovirus A71-related (EV-A71) early mortality. The purpose of this study was to measure urine catecholamine concentrations in severe EV-A71-infected children. Methods: A total of 35 children, aged 2.5 ± 2.1 years, were divided into three groups. Group I: 15 septic shock patients, group II: 17 EV-A71-stage-2 patients, and group III: 3 EV-A71-stage-4 patients. The laboratory results, cardiac biomarkers and urine catecholamine concentrations were statistically analysed. Results: Group I had the highest C-reactive protein (CRP) levels and group II had the lowest B-type natriuretic peptide (BNP) and its N-terminal prohormone among the groups (p = 0.039, <0.01 and <0.01, respectively). Group III patients had significantly higher urine catecholamine and troponin-I values among the groups. If urine epinephrine (Epi) >134 ug/gCr, norepinephrine (NE) >176 ug/gCr and vanillylmandelic acid (VMA) >11.7 mg/gCr were used as the cutoff points to differentiate groups II and III, the sensitivities and specificity were all 100%. Conclusions: The significantly elevated urine catecholamine concentrations in EV-A71-stage-4 patients support the hypothesis that hypercatecholaminemia-related heart failure is involved in severe EV-A71 infection. Urine catecholamines could be used as reliable biomarkers for differentiation of severe EV-A71 infection with or without heart failure and septic shock.

Antisense oligonucleotides modulate dopa decarboxylase function in aromatic l-amino acid decarboxylase deficiency.

Aromatic l-amino acid decarboxylase deficiency (AADCD), attributed to mutations in the dopa decarboxylase (DDC) gene, is a rare neurometabolic disease resulting from a defect in the biosynthesis of dopamine and serotonin. The DDC c.714+4A>T mutation is the most prevalent mutation among patients with AADCD, and is also a founder mutation among Taiwanese patients. In this study, the molecular consequences and function of this mutation were examined in AADCD patient-derived lymphoblastoid cells. We identified novel DDC mRNA isoforms spliced with a new exon (exon 6a) in normal and c.714+4A>T lymphoblastoid cells. In addition, we identified the SR proteins (SRSF9 and SRSF6), as well as cis-elements involved in modulating the splicing of this mutated transcript. Notably, we demonstrated that antisense oligonucleotides (ASOs) were able to restore the normal mRNA splicing and increase the level of DDC protein, as well as its downstream product serotonin, in lymphoblastoid cells derived from the patient with AADCD, suggesting that these ASOs might represent a feasible alternative strategy for gene therapy of AADCD in patients with the common c.714+4A>T mutation.

Epileptic seizure in primary intracranial sarcoma: a case report and literature review.

PURPOSE: The aim of this study is to describe epileptic seizures in patients with primary intracranial sarcomas. METHODS: We report a 17-year-old girl diagnosed with primary high-grade intracranial sarcoma with initial clinical manifestation of nonconvulsive status epilepticus. Literature reports between 2000 and 2014, relevant to primary intracranial sarcomas in children, were reviewed. The clinical presentations and neurological outcomes were analyzed. RESULTS: Eleven of 29cases (38 %), 8 males and 3 females, who exhibited epileptic seizures as one of the initial symptoms and diagnosed with primary intracranial sarcomas were collected. The median age of disease onset was 5 years. The two most common seizure types were generalized seizures (45 %) and status epilepticus (36 %). Nine of 11 patients (82 %) had tumor growth involving the frontal lobe. Nine cases had the median duration of follow-up 1.7 years, of which 6 cases showed tumor recurrence and 3 cases died during the period of follow-up. CONCLUSIONS: Epileptic seizures as one of the clinical manifestations are uncommon. The two most common seizure types were generalized seizures and status epilepticus. The most frequent location of primary intracranial sarcoma-related seizures was the frontal lobe. The clinical outcome varied.

The Impact of Anti-Epileptic Drugs on Growth and Bone Metabolism.

Epilepsy is a common neurological disorder worldwide and anti-epileptic drugs (AEDs) are always the first choice for treatment. However, more than 50% of patients with epilepsy who take AEDs have reported bone abnormalities. Cytochrome P450 (CYP450) isoenzymes are induced by AEDs, especially the classical AEDs, such as benzodiazepines (BZDs), carbamazepine (CBZ), phenytoin (PT), phenobarbital (PB), and valproic acid (VPA). The induction of CYP450 isoenzymes may cause vitamin D deficiency, hypocalcemia, increased fracture risks, and altered bone turnover, leading to impaired bone mineral density (BMD). Newer AEDs, such as levetiracetam (LEV), oxcarbazepine (OXC), lamotrigine (LTG), topiramate (TPM), gabapentin (GP), and vigabatrin (VB) have broader spectra, and are safer and better tolerated than the classical AEDs. The effects of AEDs on bone health are controversial. This review focuses on the impact of AEDs on growth and bone metabolism and emphasizes the need for caution and timely withdrawal of these medications to avoid serious disabilities.

Targeting New Candidate Genes by Small Molecules Approaching Neurodegenerative Diseases.

Neurodegenerative diseases (NDs) are among the most feared of the disorders that afflict humankind for the lack of specific diagnostic tests and effective treatments. Understanding the molecular, cellular, biochemical changes of NDs may hold therapeutic promise against debilitating central nerve system (CNS) disorders. In the present review, we summarized the clinical presentations and biology backgrounds of NDs, including Parkinson's disease (PD), Huntington's disease (HD), and Alzheimer's disease (AD) and explored the role of molecular mechanisms, including dys-regulation of epigenetic control mechanisms, Ataxia-telangiectasia-mutated protein kinase (ATM), and neuroinflammation in the pathogenesis of NDs. Targeting these mechanisms may hold therapeutic promise against these devastating diseases.

Modality and children's scope understanding.

This study intends to shed light on the inconclusive argument pertaining to children's acquisition of logical form (LF) operation. Specifically, we examined children's interpretations of sentences with the ambiguous modal verb yinggai 'should,' like 'Xiaohua yinggai shangchuang shuijiao le', whose meanings depend on the landing sites of yinggai at LF (root interpretation: Xiaohua is obligated to go to bed now. epistemic interpretation: It is the case that Xiaohua has gone to bed.). The results of truth value judgment task from 15 children (range: 4;8-6;2, mean: 5;4) and 37 adults indicate that both groups tend to interpret the ambiguous yinggai as epistemic readings and that children's interpretation is adult-like. Thus, this study supports (Syrett and Lidz's in Lang Acquis 16:67-81, 2009) view that 5-year-olds have adult-like LF development and their difficulties in interpreting covert movements may be reduced to extra-grammatical factors.

Resolving unsolved whole-genome sequencing data in paediatric neurological disorders: a cohort study.

OBJECTIVE: To resolve unsolved whole-genome sequencing (WGS) data in individuals with paediatric neurological disorders. DESIGN: A cohort study method using updated bioinformatic tools, new analysis targets, clinical information and literature databases was employed to reanalyse existing unsolved genome data. PARTICIPANTS: From January 2016 to September 2023, a total of 615 individuals who aged under 18 years old, exhibited neurological disorders and received singleton WGS were recruited. 364 cases were unsolved during initial WGS analysis, in which 102 consented to reanalyse existing singleton WGS data. RESULTS: Median duration for reanalysis after initial negative WGS results was 2 years and 4 months. The diagnostic yield was 29 of 102 individuals (28.4%) through reanalysis. New disease gene discovery and new target acquisitions contributed to 13 of 29 solved cases (44.8%). The reasons of non-detected causative variants during initial WGS analysis were variant reclassification in 9 individuals (31%), analytical issue in 9 (31%), new emerging disease-gene association in 8 (27.6%) and clinical update in 3 (10.3%). The 29 new diagnoses increased the cumulative diagnostic yield of clinical WGS in the entire study cohort to 45.5% after reanalysis. CONCLUSIONS: Unsolved paediatric WGS individuals with neurological disorders could obtain molecular diagnoses through reanalysis within a timeframe of 2-2.5 years. New disease gene, structural variations and deep intronic splice variants make a significant contribution to diagnostic yield. This approach can provide precise genetic counselling to positive reanalysis results and end a diagnostic odyssey.

Cerebellar atrophy in genetic epileptic encephalopathies: A cohort study and a systematic review.

OBJECTIVE: To analyze cerebellar atrophy in genetic epileptic encephalopathies (EEs). METHODS: This research included a retrospective cohort study conducted from January 2016 to December 2023 and a systematic review on cerebellar atrophy in genetic EEs. Pediatric individuals who were diagnosed with EEs based on electroclinical features, carried causative gene variants, and exhibited cerebellar atrophy were recruited. Electroclinical features, neuroimaging findings, and causative variants of eligible individuals were analyzed. RESULTS: The cohort study showed 10 of 67 pediatric individuals (10/67; 15 %) who were diagnosed with genetic EEs had cerebellar atrophy; and 6 of the 10 individuals (6/10; 60 %) exhibited cerebellar signs. Diagnostic delay between the detection of cerebellar atrophy and the identification of genetic diagnosis existed in 6 individuals (6/10; 60 %) and the median duration was 4.4 years. A total of 32 genes, including 31 genes from the literature review and a newly identified SCN2A gene in this cohort, were reported associated with cerebellar atrophy in genetic EEs. Twenty-six genes (26/32; 81 %) accounted for cerebellar atrophy associated with other brain anomalies and 6 genes (6/32; 19 %) caused isolated cerebellar atrophy. Twenty-five genes (25/32; 78 %) showed late-onset cerebellar atrophy identified after the age of 1 year old. CONCLUSION: Cerebellar atrophy is not uncommon in genetic EEs and may serve as an indicator for molecular diagnosis in clinical practice. To shorten the diagnostic delay, follow-up neuroimaging study is crucial because of high rate of clinico-radiological dissociation and late-onset cerebellar atrophy in this patient group.

Long-Term Outcome of Pediatric Patients with Anti-NMDA Receptor Encephalitis in a Single Center.

BACKGROUND: Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is the most common autoimmune encephalitis in children. There is a high probability of recovery if treated promptly. We aimed to analyze the clinical features and long-term outcomes of pediatric patients with anti-NMDA receptor encephalitis. METHOD: We conducted a retrospective study with definite diagnoses of anti-NMDA receptor encephalitis in 11 children treated in a tertiary referral center between March 2012 and March 2022. Clinical features, ancillary tests, treatment, and outcomes were reviewed. RESULTS: The median age at disease onset was 7.9 years. There were eight females (72.7%) and three males (27.3%). Three (27.3%) patients initially presented with focal and/or generalized seizures and eight (72.7%) with behavioral change. Seven patients (63.6%) revealed normal brain MRI scans. Seven (63.6%) had abnormal EEG results. Ten patients (90.1%) received intravenous immunoglobulin, corticosteroid, and/or plasmapheresis. After a median follow-up duration of 3.5 years, one patient was lost to follow-up at the acute stage, nine (90%) had an mRS ≤ 2, and only one had an mRS of 3. CONCLUSIONS: With the early recognition of anti-NMDA receptor encephalitis based on its clinical features and ancillary tests, we were able to treat patients promptly with first-line treatment and achieve favorable neurological outcomes.

Clinico-Radiological Phenotype of UBTF c.628G>A Pathogenic Variant-Related Neurodegeneration in Childhood: A Case Report and Literature Review

Background: This work aims to describe the clinico-radiological phenotype of UBTF c.628G>A (p.Glu210Lys) pathogenic variant-related neurodegeneration in childhood. Methods: We describe the progress of clinical and neuroimaging features in a male individual who had childhood-onset neuroregression and carried the heterozygous UBTF c.628G>A (p.Glu210Lys) pathogenic variant. Clinical cases reported in the literature are reviewed. Results: Fifteen individuals, from 14 reported cases and the index case, were noted. The median age at onset of neurodegeneration was 3 years. Clinical phenotype was consistent among the affected individuals, with progressive motor, speech, cognitive, and social−emotional regression together with ataxia and prominent pyramidal and extrapyramidal symptoms and signs in early to middle childhood. All individuals had the same brain MRI features in terms of symmetric and diffuse T2 high signal intensity over the bilateral subcortical, periventricular, and peritrigonal white matter and progressive cortical and subcortical supratentorial atrophy. Two individuals were reported to have bilateral thalamic involvement. All individuals had profound intellectual disability with loss of verbal and/or ambulatory functions during follow-up. Conclusions: Individuals with the heterozygous UBTF c.628G>A (p.Glu210Lys) pathogenic variant had consistent clinical progress and neuroimaging features. Familiarity with this clinico-radiological phenotype may allow earlier diagnosis of this rare disease.

Intrafamilial phenotypic variability in TBC1D24-TLDc homozygous pathogenic variant-related developmental and epileptic encephalopathy.

OBJECTIVE: To describe intrafamilial phenotypic variability in rare TBC1D24-TLDc homozygous pathogenic variant-related developmental and epileptic encephalopathy (DEE). METHODS: Four individuals from two unrelated families who had been diagnosed with DEE caused by TBC1D24-TLDc homozygous c.1499C>T (p.A500V) pathogenic variant were recruited. RESULTS: The age of seizure onset ranged from 1 to 7 months. All four individuals exhibited very prolonged multifocal myoclonus or focal clonic fits, and the interictal EEGs were prone to dissociation with clinical seizures. The common precipitating factors for seizures were viral infection and fever. Two individuals from family II had progressive cerebellar atrophy: one had ataxia and the other one had no cerebellar signs clinically. All individuals had pharmaco-resistant epilepsy. However, the younger siblings of the two sibling pairs had normal neurodevelopmental outcomes. CONCLUSION: Intrafamilial phenotypic variability of cerebellar neurodegeneration on neuroimages and neurodevelopmental outcomes might be noted in individuals with TBC1D24-TLDc homozygous c.1499C>T (p.A500V) pathogenic variant-related DEE.

Obscure manifestations of Salmonella subdural empyema in children: case report and literature review.

PURPOSE: Salmonella intracranial infections, including subdural empyema and brain abscess, are rare clinical manifestations in children. The aim of this study is to investigate the clinical course of Salmonella subdural empyema in infants and children. METHODS: We report a 9-month-old female infant diagnosed as Salmonella subdural empyema with clinical features of prolonged fever for more than 2 months and episodic focal seizures. Literature published between 1986 and 2010 relevant to Salmonella subdural empyema in children were reviewed. The clinical presentations and laboratory findings were analyzed. RESULTS: Seventeen cases with Salmonella subdural empyema, including our index case, has been reported with detailed clinical presentation. Fever (17/17; 100%), symptoms and signs of increased intracranial pressure (8/17; 47%), seizures (8/17; 47%), and limb paralysis (8/17; 47%) were the most frequent clinical features. Among these cases, unknown causative organism prior to surgery (11/17; 65%) and prolonged fever for more than 3 weeks (5/17; 29%) were also noticed. Sixteen out of 17 patients (94%) required surgical intervention for treatment. The morbidity rate and mortality rate were 29% (5/17) and 6% (1/17), respectively. CONCLUSION: Subdural empyema is considered to be a disease with rapid progression. However, the cases caused by Salmonella species may present a slow disease course. Surgical intervention is sometimes the only way to detect the pathogen.

SCN8A Encephalopathy: Case Report and Literature Review.

Epileptic encephalopathy is a condition resulting from extreme forms of intractable childhood epilepsy. The disease can cause severe delays in cognitive, sensory, and motor function development, in addition to being fatal in some cases. Missense mutations of SCN8A, which encodes Nav1.6, one of the main voltage-gated sodium channel subunits in neurons and muscles, have been linked to early infantile SCN8A encephalopathy. Herein, we report the case of a 5-month-old girl with SCN8A encephalopathy with a novel missense mutation. Apart from intractable seizures and autistic phenotypes, the results of blood and biochemical tests, electroencephalogram (EEG) results, and brain magnetic resonance imaging (MRI) results were all normal. As the phenotypes caused by these mutations cannot be identified by any clinical, neuroimaging, or electrophysiological features, genetic sequencing should be considered to identify the underlying genetic causes. Although phenytoin is recommended as a last-resort treatment for SCN8A encephalopathy, the administration of the oxcarbazepine, instead of phenytoin, mitigated this patient's intractable seizures.

Clinical Characteristics of Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-Like Episodes.

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome, a maternally inherited mitochondrial disorder, is characterized by its genetic, biochemical and clinical complexity. The most common mutation associated with MELAS syndrome is the mtDNA A3243G mutation in the MT-TL1 gene encoding the mitochondrial tRNA-leu(UUR), which results in impaired mitochondrial translation and protein synthesis involving the mitochondrial electron transport chain complex subunits, leading to impaired mitochondrial energy production. Angiopathy, either alone or in combination with nitric oxide (NO) deficiency, further contributes to multi-organ involvement in MELAS syndrome. Management for MELAS syndrome is amostly symptomatic multidisciplinary approach. In this article, we review the clinical presentations, pathogenic mechanisms and options for management of MELAS syndrome.

Optimal Use of Perampanel in Asian Patients with Epilepsy: Expert Opinion.

Perampanel is a once-daily, first-in-class AMPA receptor antagonist approved for the treatment of epilepsy and exhibits broad-spectrum efficacy in a range of seizure types when used as both monotherapy and adjunctive therapy. Clinical studies and real-world evidence have demonstrated the advantages of initiating perampanel at low doses and utilizing a slow titration strategy. Initiating perampanel at an early stage has also been shown to be associated with better patient outcomes. However, the optimal use and place of perampanel in clinical practice has not yet been clearly defined for the Asian patient population. Use of perampanel in clinical practice varies markedly across the Asia region because of variation in knowledge, attitudes, and practice. There is currently no specific guidance on best practices for prescribing perampanel in Asian patients or how to optimize treatment strategies to maximize adherence. A group of epilepsy experts attended a virtual meeting in September 2020 to discuss their experience with using perampanel in the Asian practice setting, including their views regarding appropriate patient populations, optimal starting and maintenance doses, optimal titration regimens, key barriers to adherence, and prevention and management of adverse events. This article summarizes key clinical and real-world evidence for perampanel and consolidates the experts' opinions on optimization of perampanel prescribing and adherence in real-world practice, providing practical strategies for clinicians to implement to improve outcomes for people with epilepsy in Asia.