Opinions on the nomenclature of familial cortical myoclonic tremor with epilepsy / 中华神经科杂志

Familial cortical myoclonic tremor with epilepsy (FCMTE) is a rare neurological disorder. There were more than 10 different terms of disease name in domestic and international published articles by searching FCMTE from PubMed and Wanfang database (from 1990 to 2022), which indicated the different understanding of the disease. It is necessary to discuss the correct and consentaneous name of the disease to facilitate the professional investigation in the future. The name evolution of FCMTE and the author′s views are described in this article.

Lipofuscinosis ceroidea neuronal 6 (enfermedad Kufs tipo A): Reporte de caso en Colombia / Neuronal ceroid lipofuscinosis 6 (Kufs disease Type A): Case report from Colombia

RESUMEN INTRODUCCIÓN: Las lipofuscinosis ceroideas neuronales (CLN) son un grupo de enfermedades neurodegenerativas de inicio generalmente en la infancia, caracterizadas por acumulación intracelular de material de almacenamiento autofluorescente. En la última década se han identificado 14 formas de CLN con mutaciones en 13 genes (CLN1-CLN14), en la CLN9 no se ha identificado aún el gen. Los pacientes con mutaciones en el gen CLN6 localizado en el cromosoma 15q21-23 presentan tres tipos de variantes clínicas: CLN6 infantil tardía, con presentación entre 18 meses a 8 años, las variantes Kufs tipo A y Kufs tipo B de inicio en adolescentes y adultos. REPORTE DE CASO: Se presenta el caso de un paciente con epilepsia generalizada de inicio en la edad adulta, que ingresa a valoración en primera ocasión, con resonancia magnética cerebral con atrofia cortical leve; la enfermedad se inició a los 14 años con déficit cognitivo lentamente progresivo, sin compromiso visual; con posterior identificación genética de una variante patogénica en el gen CLN6, con un conjunto de la variante clínica Kufs tipo A de lipofuscinosis ceroidea neuronal 6 (CLN6). DISCUSIÓN: Este es el primer reporte de CLN6 con variante clínica Kufs tipo A en Colombia. Con el advenimiento de técnicas genéticas se pueden hacer diagnósticos específicos de CLN6, a partir de la clínica y sospecha diagnóstica; utilizando métodos no invasivos.

ABSTRACT INTRODUCTION: Neuronal ceroid lipofuscinosis (CLN) is a group of neurodegenerative diseases generally with onset in childhood, characterized by intracellular accumulation of autofluorescent storage material. In the last decade, 14 forms of CLN have been identified with mutations in 13 genes (CLN1-CLN14), in CLN9 the gene has not yet been identified. Patients with mutations in the CLN6 gene located on chromosome 15q21-23 present three types of clinical variants: late childhood CLN6, presenting between 18 months to 8 years, the Kufs type A and Kufs type B variants of onset in adolescents and adults. CASE REPORT: We present the case of a male patient with generalized epilepsy of onset in adulthood, who was admitted for evaluation the first time, with brain magnetic resonance imaging with mild cortical atrophy; he started at age 14 with slowly progressive cognitive deficit, without visual compromise; with subsequent genetic identification of a pathogenic variant in the CLN6 gene, jointly presenting the clinical variant Kufs type A of neuronal ceroid lipofuscinosis 6 (CLN6). DISCUSSION: This is the first report of CLN6 with Kufs type A clinical variant in Colombia. With the advent of genetic techniques, specific diagnoses of CLN6 can be made, based on the clinical and suspected diagnoses; using non-invasive methods.

Clinical and electrophysiological study of familial cortical myoclonic tremor with epilepsy with fixation-off sensitivity / 中华神经科杂志

Objective:To discuss the clinical and electrophysiological characteristics of familial cortical myoclonic tremor with epilepsy (FCMTE) with fixation-off sensitivity (FOS).Methods:The clinical and electrophysiological characteristics of four patients diagnosed as FCMTE with FOS in the Electroencephalography (EEG) Monitoring Center of Xijing Hospital from May 2016 to December 2017 were studied and followed up.Results:The four patients were all female. The age was ranged from 29 to 67 years. The course was from six to 30 years, and the follow-up time was at least two years. The tremors and jerks occurred to the four patients frequently when the eyes were closed, which prevented their falling a sleep, and three of them had generalized tonic-clonic seizure occasionally. The FOS was monitored in the all four patients, and the photosensitivity occured to the three of them.Conclusions:The fixation-off sensitive trail during EEG monitoring is helpful to find the FCMTE with FOS. It is necessary to determine the potential clinical significance of FOS and photosensitivity coexisting in patients with FCMTE.

Epilepsia refractaria con convulsiones febriles plus en niños con mutaciones de la subunidad alfa de canales de sodio (SCN1A): un reporte de caso / Refractory epilepsy with febrile seizures in a child with sodium channel alpha subunit mutation (SCN1A): A case report

RESUMEN Se presenta caso de una niña de 10 años con cuadro de epilepsia mioclónica juvenil severa en la infancia, que a los 6 meses de edad debutó con crisis tónico-clónicas generalizadas (TCG) luego de la administración de una dosis de vacuna DPT, con posteriores crisis TCG, mioclónicas y múltiples episodios de estado epiléptico refractarios a fármacos antiepilépticos (FAE) de primera y segunda línea durante los primeros 5 años. Las crisis se asociaron a retraso global en el desarrollo luego del primer episodio. Durante la evolución se realizaron estudios que incluyen resonancia magnética cerebral que fue normal y tomografía por emisión de positrones (PET-CT) que evidenció alteraciones en el metabolismo en región temporal izquierda, además de estudios para inmunodeficiencias y trombofilias sin alteraciones. Los electroencefalogramas iniciales fueron normales, pero video electroencefalograma de 12 horas mostró actividad irritativa en la región central con diseminación bilateral. Los estudios genéticos identificaron una mutación en el marco de lectura de tipo "frameshift" del gen SCN1A mediante secuenciación de la región codificante. Luego de los primeros años de vida, la paciente presenta, atípicamente, remisión progresiva de las crisis con posterior desmonte de FAE y mejoría del neuro-desarrollo en el proceso interdisciplinario de rehabilitación.

SUMMARY We report the case of a 10-year-old female with a history of severe myoclonic epilepsy of infancy who presents with generalized tonic-clonic (GTC) seizures at 6 months of age after administration of a DPT vaccine, who then begins to present frequent and severe GTC seizures, myoclonic seizures and multiple refractory status epilepticus poorly controlled with first and second line anti-epileptic drugs (AEDs). This was accompanied by development delay. Studies performed on the patient included brain MRI which was normal, immunodeficiency and trombophilic studies which were normal and electroencephalographs: studies (EEG) that were at first mostly normal. The most significant findings were seen during a 12-hour video-EEG which reported epileptogenic activity in central region with bilateral dissemination and a PET-CT that showed metabolism alterations in the left temporal region. Due to this presentation a channelopathy was suspected and a coding region sequentiation study was performed which identified a frameshift mutation of the SCN1A gene confirming the diagnosis. Atipically, after 5 years the patient begins to present a favorable evolution with significant seizure remission even allowing the progressive weaning of AEDs and a remarkable stalemate of developmental delay after interdisciplinary rehabilitation process was started.

Clinical features and genetic characteristics of myoclonic-atonic epilepsy caused by SLC6A1 gene mutation / 中国医师杂志

Objective@#To explore the clinical features and genetic characteristics of myoclonic-atonic epilepsy (MAE) caused by SLC6A1 gene mutation.@*Methods@#The clinical data of a patient with SLC6A1 gene mutation from Xiangya Hospital of Central South University was collected. The related literatures were reviewed from Wanfang Data, China National Knowledge Infrastructure, PubMed (until July 2019) by using keywords " SLC6A1" and " myoclonic-atonic epilepsy" . The characteristics of SLC6A1 gene mutation and the clinical phenotype of children with myoclonic-atonic epilepsy were summarized.@*Results@#A 8 year and 8 months old girl was enrolled in the study. Her first attack happened at the age of 19 months, and multiple seizure types including myoclonic-atonic, atonic and absence were observed. The seizures were well controlled by valproate (VPA), but she has mild-moderate intellectual disability. Whole exome-sequencing study identified a de novo nonsense variant of c. 46G>T(p.Glu16*)in SLC6A1 gene. A total of 27 cases including the present case with SLC6A1 gene mutation were analyzed. 22 mutations were identified, including 11 missense mutations, 5 nonsense mutations, 3 frameshift mutations, 2 splicing mutation and 1 with chromosome microdeletion. Among them 26 patients had more one type of seizures, 20 cases had absence seizures, 17 cases had atonic seizures, 14 cases had myoclonic seizures, 11 cases had myoclonic-atonic seizures, 4 cases had generalized tonic-clonic seizures, 3 cases had eyelid myoclonias, 2 cases had nonconvulsive status epilepticus and 2 cases had tonic seizure. 24 patients had described intelligence assessment. Among them, 18 had developmental delay before epilepsy onset, 11 had developmental regression after onset. There were 9 cases with autistic features, 4 cases with attention deficit hyperactivity disorder and 3 cases with ataxia. The seizures of 17 cases were controlled, 4 cases had partial seizure control, 3 cases had no significant improvement, and other 3 cases were unclear.@*Conclusions@#The main clinical feature of MAE patients with SLC6A1 gene mutations is absence and atonic seizures, cognition before epilepsy onset can be impaired, and some patients had behavioral problems, such as autistic features or attention deficit hyperactivity disorders. VPA is recommend as first-line treatment.

Clinical features and genetic characteristics of myoclonic-atonic epilepsy caused by SLC6A1 gene mutation / 中国医师杂志

Objective To explore the clinical features and genetic characteristics of myoclonic-atonic epilepsy (MAE) caused by SLC6A1 gene mutation.Methods The clinical data of a patient with SLC6A1 gene mutation from Xiangya Hospital of Central South University was collected.The related literatures were reviewed from Wanfang Data,China National Knowledge Infrastructure,PubMed (until July 2019) by using keywords "SLC6A1" and "myoclonic-atonic epilepsy".The characteristics of SLC6A1 gene mutation and the clinical phenotype of children with myoclonic-atonic epilepsy were summarized.Results A 8 year and 8 months old girl was enrolled in the study.Her first attack happened at the age of 19 months,and multiple seizure types including myoclonic-atonic,atonic and absence were observed.The seizures were well controlled by valproate (VPA),but she has mild-moderate intellectual disability.Whole exome-sequencing study identified a de novo nonsense variant of c.46G ＞ T(p.Glu16 *)in SLC6A1 gene.A total of 27 cases including the present case with SLC6A1 gene mutation were analyzed.22 mutations were identified,including 11 missense mutations,5 nonsense mutations,3 frameshift mutations,2 splicing mutation and 1 with chromosome microdeletion.Among them 26 patients had more one type of seizures,20 cases had absence seizures,17 cases had atonic seizures,14 cases had myoclonic seizures,11 cases had myoclonic-atonic seizures,4 cases had generalized tonic-clonic seizures,3 cases had eyelid myoclonias,2 cases had nonconvulsive status epilepticus and 2 cases had tonic seizure.24 patients had described intelligence assessment.Among them,18 had developmental delay before epilepsy onset,11 had developmental regression after onset.There were 9 cases with autistic features,4 cases with attention deficit hyperactivity disorder and 3 cases with ataxia.The seizures of 17 cases were controlled,4 cases had partial seizure control,3 cases had no significant improvement,and other 3 cases were unclear.Conclusions The main clinical feature of MAE patients with SLC6A1 gene mutations is absence and atonic seizures,cognition before epilepsy onset can be impaired,and some patients had behavioral problems,such as autistic features or attention deficit hyperactivity disorders.VPA is recommend as first-line treatment.

Electroclinical characteristics of epilepsy children with midline epileptiform discharges related epileptic negative myoclonus as the first symptom / 中华儿科杂志

Objective@#To investigate the electroclinical findings in epilepsy children with epileptic negative myoclonus (ENM) restricted to the lower limb as the first seizure type.@*Methods@#Each retrieved electroencephalogram record performed between March 2011 and March 2018 at the Department of Pediatrics of Peking University First Hospital was searched with "midline" . There were 302 records of 175 patients with "benign" or "functional" midline spikes. A retrospective review of each patient′s hospital record was performed. Thirteen patients had ENM restricted to the lower limb as the first seizure type. The clinical and electroencephalogram characteristics of them were analyzed.@*Results@#Thirteen patients manifested ENM restricted to the lower limb as the first seizure type, diagnosed as benign childhood focal epilepsy with vertex spikes (BEVS). Six patients had ENM as the first and only seizure type during the short-time follow-up. Among them, there were 1 male and 5 females. The age at seizure onset was (2.5±0.7) years. One of them had electrical status epilepticus during sleep (ESES) identified on electroencephalogram at theage of 4 years and 8 months. The last follow-up age was (3.8±1.5) years. The remaining 7 patients developed nocturnal focal motor seizures. Among them, there were 4 males and 3 females. The age at seizure onset was (3.5±0.7) years. Two of them were diagnosed as BEVS evolving into benign childhood epilepsy with centrotemporal spikes (BECTS) and 5 were diagnosed as BEVS concurring with BECTS. The age at focal seizures was (4.1±0.6) years. The interval ranged from 1 month to 1 years. Six of 7 patients had electrical ESES with the age of (5.2±1.0) years. All had developmental regression, further diagnosed as atypical benign partial epilepsy (ABPE). The median age at last follow-up was 5.9 years. Five of 13 patients had repeated electroencephalogram records at our apartment, showing that epileptiform discharges in midline regions were significantly reduced either in frequency or amplitude with the improvement of ENM restricted to the lower limb and that independent epileptiform discharges in Rolandic regions from midline regions were noticed with the onset of nocturnal focal seizures.@*Conclusions@#ENM restricted to the lower limb has a close association with vertex (midline) epileptiform discharges. ENM restricted to the lower limb as the first seizure type is a peculiar phenomenon of BEVS. Some patients could evolve into BECTS or overlap with BECTS, and further into ABPE. The age of seizure onset in BEVS with ENM restricted to the lower limb as the first symptom is a little earlier than in BECTS. Ignorance of the close association between midline spikes and ENM restricted to the lower limb may lead to misdiagnosis of these patients.

Progresses of magnetic resonance spectroscopy in thalamo-cortical network of juvenile myoclonic epilepsy / 中国医学影像技术

Juvenile myoclonic epilepsy (JME) diagnosed with seizure history,semiology and electroencephalography is a syndrome of idiopathic generalized epilepsy.MRS can quantitatively detect the concentration of neurometabolites noninvasively,and assess the metabolic changes in brain.Currently,studies of pathogenesis of JME are focused on the dysfunction of thalamo-cortical network and the neurometabolites and imbalance of Glutamate and γ-aminobutyric acid in the network are alterted.Epilepsy is associated with the imbalance of the ratio of excitatory and inhibitory amino acid,and seizures lead to neuronal lesions which result in altered concentration of neuron related metabolites.This article reviewed MRS studies of JME by combining material metabolism,neural structure and function.

Mutation analysis of CSMD3 gene in a pedigree of familial cortical myoclonic tremor with epilepsy / 中国医师杂志

Objective To investigate mutations of CSMD3 gene in a pedigree of familial cortical myoclonic tremor with epilepsy (FCMTE).Methods Peripheral blood (5 ml) was obtained from FCMTE patients (7 cases),suspected cases,and control individuals.Polymerase chain reaction (PCR) and purification of PCR products for sequencing were used to detect the existence of mutations in 73 exons of gene CSMD3.The resulting products were subjected to agarose gel electrophoresis and gel-imaging system.The PCR amplification products were sequenced.Results The sequencing results of 73 exons were compared with CSMD3gDNA sequence in human GenBank.We neither found any DNA sequence variation nor disease-related mutations.Conclusions The family does not have a mutation in the CSMD3 gene.We need to further find the disease genes and the mutations in this family.

Clinical-electroencephalogram characteristics and its evolutionary process of Dravet syndrome / 中华神经科杂志

Objective To analyze the clinical and electroencephalogram (EEG) characteristics as well as its evolutionary process of Dravet syndrome (DS) in order to improve early diagnosis and appropriate treatment.Methods Fifty patients with DS were studied including onset age, trigger factors, seizure types on different age stages and relationship with EEG characteristics and its evolution process.Results The average age of seizure onset was ( 5.5 ± 1.9 ) months.The fever sensitivity continuously existed in the entire course of disease.In the early stage, generalized tonic-clonic seizures (GTCS) and focal or unilateral seizures were main types.Multi seizure types included myoclonic seizures (MS) and atypical absence occurred later.The onset ages of MS were average (M50) of 16 months.MS never occurred in 26% of the patients.During the first year of life, EEGs were normal in 76% of these patients.The epileptiform discharges only recorded in about 50% of the patients in spite of multi seizure types had presented.After three years ago, both EEG background abnormalities and discharges occurred in more 90% of the all patients.Photosensitivity response with MS occurred in the 28% of 18 patients.Conclusions The clinical and EEG are not parallel progressively process in early stage of DS.The children often express more severe clinical seizures than EEG abnormalities until 2 years of age.Various abnormal EEG manifestation obviously display gradually after 3 years age.Precise recognizing with the clinical and EEG characteristics of DS will help get correct early diagnosis and screen the candidate cases to test SCN1A gene.

De novo sodium channel αl-subuult mutation of monozygotic twins with borderland severe myoclonic epilepsy in infancy / 中华神经科杂志

Objective To study the sodium channel α1-subunit (SCN1A) gene in a pair of monozygotic twins with borderland severe myoclonic epilepsy in infancy (SMEB) and its characteristic of clinical manifestations. Methods The clinical features of 2 monozygotic twins were summarized. All 26 exons of SCNIA genes were screened with denaturing high performance liquid chromatography (DHPLC), and direct sequence analysis was performed on those with abnormal elution peak. Results The proband and her sister showed typical clinical features of SMEB. The same heterozygous mutations on exon 26 which caused the related amino acid change were found among them (c. 5348C > T, A1783E). Conclusion Monozygotic twins with similar clinical phenotype of SMEB have same SCN1A gene mutation.

Features of clinical and therapy in juvenile myoclonic epilepsy: an analysis of 87 cases / 中华神经科杂志

Objective To analyze clinical characteristics of patients with juvenile myoclonic epilepsy in China. Methods Eighty-seven patients were retrospectively studied in the aspects of family history, febrile seizures, clinical features, EEG, treatment effect. Results There was a female preponderance of incidence. In contrast to the earlier studies we found a high incidence of febrile seizures and a low incidence of family history. myoclonic seizures began at age of ( 13.1?3.4) years. That combined with generalized tonoclonic seizures began at age (14.3?3.8) years. Absence seizures began at age (10.0?3.3) years. The correct diagnosis was delayed at a mean of 2.2 years from onset of the disease. The incidence of abnormal EEG discharge could be enhanced by hyperventilation, photic stimulation and sleep. Sixteen patients who had received carbamazepine or phenytoin were experienced aggravation of seizures. Forty-five patients who received monotherapy with sodium valproate remained seizure-free in a follow-up longer than 0.5 years. Conclusions Failure to recognize JME may result in uncontrolled seizures, and even aggravated of seizures by using antiepilepsy drugs. Effective treatment was achieved with small doses of sodium valproate.