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Wolf-Hirschhorn syndrome (WHS) is araredisorderwithan estimated prevalence being around 1 in 50,000 births. The syndrome is caused by the deletion of a critical region (Wolf-Hirschhorn Syndrome Critical region- WHSCR) on chromosome 4p16.3. WHS is clinically characterized by pre-and postnatal growth restriction, hypotonia, intellectual disability, craniofacial dysmorphismand congenital fusion anomalies. The clinical aspects are variable due to the deletion size.Consistently, epilepsy is one of the major concerns for parents and professionals caring for children with WHS. Seizures tend to occur in over 90% of patients, with onset within the first 3 years of life, and a peak incidence at around 6-12 months of age. Approximately 20% of patients had the first seizure onset within the first 6 months of age, almost 50% at 6 to 12 months of age and about 25% later than 12 months of age. The main types of epileptic seizures occurring in patients with WHS were generalized tonic-clonic seizures (around 70%). These were followed by tonic spasms (20%); focal seizures with impaired awareness (12%) and clonicseizures in 7% of patients.Seizures are often triggered by fever, followed by infections of various systems. Particularly, half of WHS patients experience status epilepticus in the first years of life, which can be fatal. Due to limited number of reports on the topic of EEG abnormalities in epilepsy among WHS patients, it is difficult to determine whether there are any characteristic deviations for WHS. Although more than 300 persons with WHS have been reported in the literature, there is sparse knowledge about epilepsy and methods of its anti-seizure medication (ASM) management with an assessment of their effectiveness. The purpose of this systematic review is to briefly summarize achievements and advances in the field of epilepsy in Wolf-Hirschhorn syndrome.
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BACKGROUND: Neuronal autoantibodies and favorable response to immunosuppressive treatment have been described in patients with chronic epilepsy of unknown cause, suggesting autoimmune etiology. Our aim was to identify novel epilepsy-specific autoantibodies reactive with neuronal surface antigens. METHODS: Sera of 172 epilepsy patients with unknown cause and 30 healthy controls were screened with indirect immunofluorescence to identify IgG reacting with primary rat neuronal cultures. Putative target autoantigens were investigated with immunoprecipitation (IP) and liquid chromatography-mass/mass spectrometry (LC-MS/MS) studies using SH-SY5Y cells. Validation of LC-MS/MS results was carried out by IP and immunocytochemistry assays. RESULTS: Antibodies to neuronal cell surface antigens were detected in 18 epilepsy patients. LC-MS/MS analysis identified voltage-gated potassium channel modifier subfamily F member 1 (KCNF1, Kv5.1) as the single common cell surface antigen in 4 patients with Lennox-Gastaut syndrome (n = 2), focal epilepsy of unknown cause (n = 1) and mesial temporal lobe epilepsy with hippocampal sclerosis (n = 1). These patients had the common features of early seizure onset and treatment-resistance. IP assays and co-localization (serum IgG and commercial Kv5.1-antibody) studies done with non-fixed Kv5.1-transfected HEK293 cells and primary neuronal cultures confirmed the presence of Kv5.1-antibody in 4 epilepsy patients identified by LC-MS/MS. Similar findings were not obtained by sera of other patients with epilepsy, patients with autoimmune encephalitis and healthy controls. CONCLUSION: The herein described novel neuronal surface antibody to Kv5.1 appears to be associated with treatment-resistant epilepsy of unknown cause. Exact clinical and pathogenic significance of this antibody remains to be elucidated.
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Epilepsia , Espectrometría de Masas en Tándem , Animales , Autoanticuerpos , Cromatografía Liquida , Células HEK293 , Humanos , Inmunoglobulina G , RatasRESUMEN
BACKGROUND: The genetic and epidemiological features of hereditary ataxias have been reported in several populations; however, Turkey is still unexplored. Due to high consanguinity, recessive ataxias are more common in Turkey than in Western European populations. OBJECTIVE: To identify the prevalence and genetic structure of hereditary ataxias in the Turkish population. METHODS: Our cohort consisted of 1296 index cases and 324 affected family members. Polymerase chain reaction followed by Sanger sequencing or fragment analysis were performed to screen for the trinucleotide repeat expansions in families with a dominant inheritance pattern, as well as in sporadic cases. The expansion in the frataxin (FXN) gene was tested in all autosomal recessive cases and in sporadic cases with a compatible phenotype. Whole-exome sequencing was applied to 251 probands, selected based on the family history, age of onset, and phenotype. RESULTS: Mutations in known ataxia genes were identified in 30% of 1296 probands. Friedreich's ataxia was found to be the most common recessive ataxia in Turkey, followed by autosomal recessive spastic ataxia of Charlevoix-Saguenay. Spinocerebellar ataxia types 2 and 1 were the most common dominant ataxias. Whole-exome sequencing was performed in 251 probands with an approximate diagnostic yield of 50%. Forty-eight novel variants were found in a plethora of genes, suggesting a high heterogeneity. Variants of unknown significance were discussed in light of clinical data. CONCLUSION: With the large sample size recruited across the country, we consider that our results provide an accurate picture of the frequency of hereditary ataxias in Turkey. © 2021 International Parkinson and Movement Disorder Society.
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Atrofia Óptica , Ataxias Espinocerebelosas , Degeneraciones Espinocerebelosas , Humanos , Espasticidad Muscular , Turquía/epidemiologíaRESUMEN
Tuberous sclerosis (TSC) is an autosomal dominantly inherited genetic disorder that chiefly affects the central nervous system, along with the other multiple systems. While phenomenology and symptom severity may vary greatly from one individual to another, the most common neurological presentation is epilepsy, which may be refractory in a considerable number of patients. Convulsive SE is seen frequently in TSC patients due to the high ratio of refractory seizures in well-studied cohorts. Status epilepticus (SE) is a life-threating condition and requires urgent medical care. Non-convulsive status epilepticus (NCSE) is an epileptic state with no convulsive seizures but impaired consciousness and corresponding electrophysiological findings. Due to its heterogeneity of clinical features, it is generally hard to recognize, and thus difficult to treat promptly. The relationship between TSC and NCSE is a relatively less emphasized issue in the literature. Here, we present two cases of TSC with NCSE with a view to increasing clinicians' awareness of the association between refractory epilepsy and NCSE.
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Estado Epiléptico/etiología , Esclerosis Tuberosa/complicaciones , Niño , Humanos , Masculino , Estado Epiléptico/diagnósticoRESUMEN
OBJECTIVE: The long-term follow-up of patients with epilepsy harboring autoantibodies against the glycine receptor (also glycine receptor antibodies or GlyR-Ab) is not well-known. Our aim was to investigate the 5-year prognosis and treatment response of patients with epilepsy who were seropositive for GlyR-Ab. METHODS: Clinical features; electroencephalogram (EEG), neuroradiological, and neuropathological findings; and treatment responses of patients with epilepsy with GlyR-Ab seropositivity were investigated. RESULTS: Thirteen (5.46%) of 238 patients with epilepsy were GlyR-Ab positive: focal epilepsy of unknown cause (FEoUC) was diagnosed in four (7.27%) out of 55 patients, mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) in five (4.5%) out of 111 patients, epileptic encephalopathy (EE) in two (4%) out of 50 patients, and status epilepticus (SE) in two (9.09%) out of 22 patients. None of the patients developed any other neurological symptoms or cancer during the 5-year follow-up. Seven of them had seizures that were resistant to antiepileptic drug (AED). Immunotherapy was used in two patients (with FEoUC and EE) improving seizure control. Three patients with MTLE-HS benefited from epilepsy surgery, and another patient with EE showed spontaneous remission. CONCLUSION: Glycine receptor antibodies are detected in a wide spectrum of epileptic disorders with unclear pathogenic significance. Two GlyR-Ab seropositive patients with AED-resistant epilepsy treated with intravenous immunoglobulin (IVIg) showed clear benefit from immunotherapy. Future studies will be valuable in determining the role of screening patients with drug-resistant epilepsy for GlyR-Ab in order to identify patients who may benefit or respond to immunotherapy.
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Autoanticuerpos/sangre , Epilepsia/sangre , Epilepsia/tratamiento farmacológico , Inmunoglobulinas Intravenosas/uso terapéutico , Receptores de Glicina/sangre , Adulto , Biomarcadores/sangre , Epilepsia Refractaria/sangre , Epilepsia Refractaria/tratamiento farmacológico , Epilepsia Refractaria/fisiopatología , Electroencefalografía/métodos , Epilepsias Parciales/sangre , Epilepsias Parciales/tratamiento farmacológico , Epilepsias Parciales/fisiopatología , Epilepsia/fisiopatología , Epilepsia del Lóbulo Temporal/sangre , Epilepsia del Lóbulo Temporal/tratamiento farmacológico , Epilepsia del Lóbulo Temporal/fisiopatología , Femenino , Estudios de Seguimiento , Células HEK293 , Humanos , Masculino , Persona de Mediana Edad , Estado Epiléptico/sangre , Estado Epiléptico/tratamiento farmacológico , Estado Epiléptico/fisiopatología , Adulto JovenRESUMEN
AIM: Cryptogenic forms of epileptic encephalopathies (EE) with their well-known features of drug-resistance, mental deterioration and partial response to immunotherapies are ideal candidates for screening for neuronal autoantibodies (NAA). METHOD: Fifty consecutive pediatric patients with a diagnosis of EE of unknown cause were included. Nine NAAs were tested by ELISA, RIA or cell-based assays. Clinical features of seronegative and seropositive patients were compared. RESULTS: NAAs were found in 7/50 (14%) patients. They were N-methyl-d-aspartate receptor in two (4%), glycine receptor in two (4%), contactin-associated protein-like 2 in one (2%), glutamic acid decarboxylase in one (2%) and type A gamma aminobutyric acid receptor in one patient (2%). Furthermore, serum IgGs of two patients negative for well-characterized NAAs, showed strong reactivity with the uncharacterized membrane antigens of live hippocampal neurons. There were no significant differences between seropositive and seronegative patients by means of epilepsy duration, anti-epileptic drug resistance, EE type, types of seizures, seizure frequencies, EEG features or coexisting autoimmune diseases. Some seropositive patients gave good-moderate response to immunotherapy. DISCUSSION: Potential clues for the possible role of autoimmunity in seropositive patients with EE were atypical prognosis of the classical EE type, atypical progression and unusual neurological findings like dyskinesia.
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Autoanticuerpos/sangre , Epilepsia/diagnóstico , Epilepsia/inmunología , Proteínas de la Membrana/inmunología , Neuronas/inmunología , Receptores de Neurotransmisores/inmunología , Adolescente , Adulto , Niño , Preescolar , Epilepsia/sangre , Femenino , Estudios de Seguimiento , Humanos , Lactante , Síndrome de Lennox-Gastaut/diagnóstico , Síndrome de Lennox-Gastaut/inmunología , Masculino , Espasmos Infantiles/diagnóstico , Espasmos Infantiles/inmunología , Adulto JovenRESUMEN
OBJECTIVE: To provide an overview of clinical and MRI characteristics of the different variants of the leukodystrophy megalencephalic leukoencephalopathy with subcortical cysts (MLC) and identify possible differentiating features. METHODS: We performed an international multi-institutional, cross-sectional observational study of the clinical and MRI characteristics in patients with genetically confirmed MLC. Clinical information was obtained by questionnaires for physicians and retrospective chart review. RESULTS: We included 204 patients with classic MLC, 187 of whom had recessive mutations in MLC1 (MLC1 variant) and 17 in GLIALCAM (MLC2A variant) and 38 patients with remitting MLC caused by dominant GLIALCAM mutations (MLC2B variant). We observed a relatively wide variability in neurologic disability among patients with classic MLC. No clinical differences could be identified between patients with MLC1 and MLC2A. Patients with MLC2B invariably had a milder phenotype with preservation of motor function, while intellectual disability and autism were relatively frequent. Systematic MRI review revealed no MRI features that distinguish between MLC1 and MLC2A. Radiologic improvement was observed in all patients with MLC2B and also in 2 patients with MLC1. In MRIs obtained in the early disease stage, absence of signal abnormalities of the posterior limb of the internal capsule and cerebellar white matter and presence of only rarefied subcortical white matter instead of true subcortical cysts were suggestive of MLC2B. CONCLUSION: Clinical and MRI features did not distinguish between classic MLC with MLC1 or GLIALCAM mutations. Absence of signal abnormalities of the internal capsule and cerebellar white matter are MRI findings that point to the remitting phenotype.
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Quistes , Enfermedades Desmielinizantes del Sistema Nervioso Central Hereditarias , Proteínas de la Membrana/genética , Mutación/genética , Proteínas/genética , Adolescente , Proteínas de Ciclo Celular , Corteza Cerebral/diagnóstico por imagen , Niño , Preescolar , Estudios Transversales , Quistes/diagnóstico por imagen , Quistes/genética , Quistes/fisiopatología , Femenino , Enfermedades Desmielinizantes del Sistema Nervioso Central Hereditarias/diagnóstico por imagen , Enfermedades Desmielinizantes del Sistema Nervioso Central Hereditarias/genética , Enfermedades Desmielinizantes del Sistema Nervioso Central Hereditarias/fisiopatología , Humanos , Cooperación Internacional , Imagen por Resonancia Magnética , Masculino , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
Charcot-Marie-Tooth (CMT) disease is a hereditary neurologic disease which affects the sensorial and motor fibers of the peripheral nerves. CMTX1 is an X-linked dominantly inherited subtype of CMT and is caused by mutations in gap junction beta 1 gene (GJB1). A small proportion of GJB1 mutations are associated with recurrent central nervous system findings. We describe a 15-year-old male patient with CMTX1 who had stroke-like findings along with foot deformities and peripheral neuropathy. Strokes and stroke-like attacks are rarely seen in children and adolescents. Herein, neurological signs, MRI findings and genetic results of a CMTX1 case are presented and discussed.
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Enfermedad de Charcot-Marie-Tooth/genética , Ataque Isquémico Transitorio , Accidente Cerebrovascular , Adolescente , Conexinas , Humanos , Ataque Isquémico Transitorio/genética , Masculino , MutaciónRESUMEN
OBJECTIVE: Pantothenate kinase-associated neurodegeneration (PKAN) is caused by mutations of the pantothenate kinase 2 (PANK2) gene. The major clinical sign of PKAN is dystonia and the eye-of-the-tiger pattern on the MRI has been a clue for the diagnosis. We aim to discuss clinical and genetic findings of 22 PKAN patients from 13 families. METHODS: Twenty-two patients were clinically diagnosed with PKAN and screened for PANK2 mutations. The patients were classified according to their onset age and progression rate. RESULTS: Mutation screening revealed 5 novel and 7 previously reported sequence variants in PANK2. The variants identified were in the form of missense changes, small exonic deletions and intronic mutations with a probable splicing effect. The presenting features were dystonia and gait disturbance in early onset patients, whereas the presenting symptoms were variable for the late onset group. The progression rate of the disease was not uniform. CONCLUSION: The current report is the first patient series of PKAN from Turkey that expands the clinical and genetic spectrum of the disease.
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Neurodegeneración Asociada a Pantotenato Quinasa/genética , Neurodegeneración Asociada a Pantotenato Quinasa/fisiopatología , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , Edad de Inicio , Progresión de la Enfermedad , Distonía/etiología , Trastornos Neurológicos de la Marcha/etiología , Humanos , Neurodegeneración Asociada a Pantotenato Quinasa/complicaciones , Linaje , TurquíaRESUMEN
PURPOSE: Epilepsy is an important feature for neuropsychiatric involvement in systemic lupus erythematosus (SLE) with unknown mechanism. Our aim was to investigate the presence of neuronal auto-antibodies (NAbs) in neuropsychiatric SLE (NPSLE). METHODS: Eighteen SLE patients (17 females, 1 male) experiencing recurrent seizures were enrolled to this study. Their clinical characteristics, EEG and MRI findings and follow-up information were evaluated from their files. Antibodies against voltage-gated potassium channel (VGKC)-complex antigens, contactin-associated protein-like 2 (CASPR-2), leucine-rich, glioma inactivated 1 (LGI1), glutamic acid decarboxylase (GAD), N-methyl-d-aspartate receptor (NMDA-R), alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid receptor (AMPA-R) and type B gamma aminobutyric acid receptors (GABAB-R) were screened in the sera of these patients. Moreover, indirect immunohistochemistry and immunocytochemistry tests were performed to reveal neuropil antibodies. RESULTS: Six out of 18 patients (33.3%) had various forms of NAbs. Among them, one patient had antibodies against GAD, one patient with hippocampal sclerosis on MRI was CASPR-2 antibody positive, whereas the remaining four patients showed hippocampal neuropil staining. We could not find a significant difference between seropositive and seronegative groups, regarding the clinical characteristics, EEG and MRI findings. CONCLUSION: This study is the first to show hippocampal neuronal staining (4/18) reflecting antibodies against unknown neuronal cell surface antigens in SLE patients with epilepsy, besides the rare occurrence of GAD and CASPR2 antibodies. Further prospective studies are needed to search for new NAbs and uncover their pathogenic role in SLE associated with epilepsy.
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Autoanticuerpos/sangre , Epilepsia/complicaciones , Epilepsia/inmunología , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/inmunología , Adulto , Animales , Biomarcadores/sangre , Encéfalo/diagnóstico por imagen , Encéfalo/inmunología , Encéfalo/patología , Células Cultivadas , Epilepsia/sangre , Epilepsia/patología , Femenino , Estudios de Seguimiento , Humanos , Inmunohistoquímica , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Neuronas/inmunología , Neuronas/patología , Ratas , Estudios RetrospectivosRESUMEN
OBJECTIVES: Such neuropsychiatric symptoms as autism spectrum disorders, attention-deficit/hyperactivity disorder (ADHD), intellectual disability, aggression, and epilepsy are very common in patients with tuberous sclerosis complex (TSC). Everolimus, a mammalian target of rapamycin (mTOR) inhibitor, is a recent and effective treatment for TSC patients with giant cell astrocytomas and renal angiomyolipoma, and it has been shown to have a potential to reduce tumor volume. However, there is a paucity of studies on the effects of everolimus on neuropsychiatric symptoms. The aim of the present study is to describe the effects of everolimus on emotional and behavioral symptoms and refractory epilepsy in a group of patients with TSC. METHODS: Four boys and two girls (median age 16.5; range 7.5-23 years) were included in the study. Information on the clinical and treatment characteristics of the patients was gathered from the medical records. RESULTS: Median everolimus dose was 10 mg/day (range 5-20 mg) and median time for follow-up was 17.5 (range 7-26) months. The drug was well tolerated with mild adverse effects, including stomatitis (three cases), increase in triglycerides and cholesterol (two cases), and constipation (one case). The adverse effects encountered during the course of treatment did not make it necessary to discontinue the drug or decrease its dose. All cases experienced very good to moderate response for controlling epileptic seizures. Besides, improvements in social contact, language, repetitive behavior, inattention, hyperactivity, and depression were observed in some patients. CONCLUSIONS: Everolimus was well tolerated without severe adverse effects. It was helpful in controlling seizures and additional improvements were noted in autistic, ADHD, and depressive symptoms.
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Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológico , Trastorno Autístico/tratamiento farmacológico , Everolimus/uso terapéutico , Inmunosupresores/uso terapéutico , Esclerosis Tuberosa , Adolescente , Epilepsia/tratamiento farmacológico , Everolimus/efectos adversos , Femenino , Humanos , Inmunosupresores/efectos adversos , MasculinoAsunto(s)
Brucelosis/diagnóstico por imagen , Infecciones Bacterianas del Sistema Nervioso Central/diagnóstico , Imagen por Resonancia Magnética , Médula Espinal/diagnóstico por imagen , Adolescente , Adulto , Antibióticos Antituberculosos/uso terapéutico , Brucelosis/líquido cefalorraquídeo , Brucelosis/tratamiento farmacológico , Brucelosis/patología , Infecciones Bacterianas del Sistema Nervioso Central/líquido cefalorraquídeo , Infecciones Bacterianas del Sistema Nervioso Central/tratamiento farmacológico , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Persona de Mediana EdadRESUMEN
PURPOSE: We aimed to investigate juvenile myoclonic epilepsy (JME) patients complaining of tremor unrelated to valproate (VPA) treatment and evaluate if there were differences between JME patients with and without tremor and essential tremor (ET) patients to exclude comorbidity. METHODS: Fifteen JME cases with the complaint of tremor, 14 JME patients without tremor, 14 patients with ET and 14 healthy subjects (HS) were included. Regularity, frequency and amplitude of the tremor and superimposed myoclonia were assessed by accelerometric analysis. Cortical SEPs evoked by the stimulation of the median nerve were recorded bilaterally. Clinical and neurophysiologic features were statistically compared between the groups. FINDINGS: Amplitude of postural tremor of the left hand was significantly increased in the ET group compared to JME patients with tremor, but there were no differences regarding to frequency. Strikingly, there were superimposed irregular, low-amplitude inconstant myoclonic jerks located to distal part of the fingers in JME group with tremor. Initial frequency of myoclonic seizures was also significantly higher in this group compared to JME patients without tremor but this difference disappeared after treatment. The group of JME with tremor had the highest N20-P25 and P25-N35 amplitudes, followed by JME without tremor, ET and HS, respectively. CONCLUSION: Tremulous hand movements in JME resembled ET, but their amplitude was lower and characterized with accompanying irregular myoclonic jerks. The presence of tremor in JME patients should be taken into consideration to create more homogeneous groups in genetic and pathophysiological studies of JME.
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Epilepsia Mioclónica Juvenil/fisiopatología , Temblor/fisiopatología , Acelerometría , Adulto , Encéfalo/fisiopatología , Electroencefalografía , Electromiografía , Endofenotipos , Potenciales Evocados Somatosensoriales , Femenino , Estudios de Seguimiento , Mano/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Músculo Esquelético/fisiopatología , Mioclonía/fisiopatología , Reflejo/fisiología , Adulto JovenAsunto(s)
Ceramidasa Ácida/genética , Mutación , Epilepsias Mioclónicas Progresivas/genética , Estado Epiléptico/genética , Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatología , Niño , Párpados/fisiopatología , Femenino , Humanos , Atrofia Muscular Espinal/complicaciones , Atrofia Muscular Espinal/diagnóstico por imagen , Atrofia Muscular Espinal/genética , Atrofia Muscular Espinal/fisiopatología , Epilepsias Mioclónicas Progresivas/complicaciones , Epilepsias Mioclónicas Progresivas/diagnóstico por imagen , Epilepsias Mioclónicas Progresivas/fisiopatología , Fenotipo , Estado Epiléptico/complicaciones , Estado Epiléptico/diagnóstico por imagen , Estado Epiléptico/fisiopatología , Grabación en VideoRESUMEN
OBJECTIVES: Transcranial direct current stimulation (tDCS) is a non-invasive and safe method tried in drug-resistant epilepsies, in recent years. Our aim was to evaluate the effect of tDCS in patients diagnosed with mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) which is a well-known drug-resistant focal epilepsy syndrome. PATIENTS AND METHODS: Twelve MTLE-HS patients diagnosed with their typical clinical, EEG and MRI findings fulfilling the criteria for drug-resistance as suggested by the ILAE commission were included after Ethics Committee approval and their signed consent. All patients received modulated cathodal stimulation; 2mA for 30min on 3 consecutive days. All patients also received sham stimulation with the same electrode positions; designed as 60s stimulation gradually decreasing in 15s with placement of the electrodes for 30min over the stimulation side. They were followed up by standard seizure diaries and their medical treatment was not changed during the study period. Their seizure frequencies both before and after cathodal tDCS and sham stimulation were compared statistically. Adverse effects were also questioned. RESULTS: Mean age of our study group was 35.42±6.96 (6 males; median: 35.50). The mean seizure frequency was 10.58±9.91 (median=8; min-max=2-30) at the baseline and significantly decreased to 1.67±2.50 (median=0.5; min-max=0-8) after cathodal tDCS application (p=0.003). Ten patients (83.33%) had more than 50% decrease in their seizure frequencies after cathodal tDCS. Two patients (16.67%) also showed positive sham effect. Six patients (50%) were seizure-free in the post-cathodal tDCS period of one month. No adverse effect has been reported except tingling sensation during cathodal stimulation. CONCLUSION: Our small series suggested that cathodal tDCS may be used as an additional treatment option in MTLE-HS. It may be tried in TLE-HS patients waiting for or rejecting epilepsy surgery or even with ineffective surgery results. More studies are needed with large series of patients to investigate the effects of tDCS in drug resistant epilepsies.
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Epilepsia del Lóbulo Temporal/terapia , Hipocampo/patología , Evaluación de Resultado en la Atención de Salud , Estimulación Transcraneal de Corriente Directa/métodos , Adulto , Epilepsia del Lóbulo Temporal/patología , Femenino , Humanos , Masculino , Esclerosis/patologíaRESUMEN
Rasmussen's encephalitis (RE) is a rare disease with unknown pathophysiology. To disclose whether anti-neuronal autoimmunity participates in the aetiology of RE, various neuronal autoantibodies (NAAbs) were investigated in sera of patients with RE and controls. The study included five patients who fulfilled the RE diagnostic criteria (clinical, EEG, and MRI findings) as the patient group, and 50 multiple sclerosis patients and 50 healthy subjects as the control groups. Sera were evaluated for various NAAbs by radioimmunoassay or cell-based assays. All sera were also screened for uncharacterized antibodies to neuronal cell surface or synapse antigens by indirect immunofluorescence using hippocampal cell cultures. The mean age at onset of seizures was 8.3±3.4 years (range: 4-13.5) and mean follow-up time was 11.2±5.4 years (range: 5-19). All patients had unihemispheric atrophy of the cerebral cortex and epilepsia partialis continua. Two of the patients had moderate cognitive impairment, while the others were severely affected, as shown by neuropsychological testing. NAAb positivity was not detected in any of the patients. Immune aetiology is thought to have a role in RE, but the responsible players have not yet been elucidated. Our extensive antibody screening in a small number of patients does not support the presence of antigen-specific anti-neuronal autoimmunity in RE pathophysiology.
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Autoanticuerpos , Corteza Cerebral/inmunología , Encefalitis/inmunología , Epilepsia Parcial Continua/inmunología , Neuronas/inmunología , Adolescente , Atrofia/diagnóstico por imagen , Atrofia/inmunología , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/patología , Niño , Preescolar , Encefalitis/diagnóstico por imagen , Encefalitis/patología , Epilepsia Parcial Continua/diagnóstico por imagen , Epilepsia Parcial Continua/patología , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Neuronas/patología , Pruebas Neuropsicológicas , Adulto JovenRESUMEN
PURPOSE: The SCN1A gene is one of the most commonly mutated human epilepsy genes associated with a spectrum of phenotypes with variable degrees of severity. Despite over 1200 distinct mutations reported, it is still hard to draw clear genotype-phenotype relationships, since genetic and environmental modifiers contribute to the development of a particular disease caused by an SCN1A mutation. We aimed to initiate mutational screening of the SCN1A gene in Turkey and advance further our understanding of the relationship between the SCN1A sequence alterations and disease phenotypes such as GEFS+, DS and related epileptic encephalopathies. METHODS: Mutational analysis of the SCN1A gene was carried out in 46 patients with DS, late-onset DS, GEFS+ and unspecified EE using either direct Sanger sequencing of the coding regions and exon/intron boundaries or massively parallel sequencing. RESULTS: Nineteen point mutations, 12 of which were novel were identified, confirming the clinical diagnosis of the patients. Patients with a mutation (either truncating or missense) on linker regions had significantly later disease onset than patients with mutations in homology regions. The presence of SCN1A mutations in two clinically unclassified patients supported the association of SCN1A mutations with a wide range of phenotypes. CONCLUSION: The conventional Sanger sequencing method was successfully initiated for the detection of SCN1A point mutations in Turkey in epilepsy patients. Furthermore, a modified strategy of massively parallel pyro-sequencing was also established as a rapid and effective mutation detection method for large genes as SCN1A.
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Epilepsia/genética , Canal de Sodio Activado por Voltaje NAV1.1/genética , Preescolar , Análisis Mutacional de ADN , Epilepsias Mioclónicas/genética , Epilepsia Generalizada/genética , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Convulsiones Febriles/genética , TurquíaRESUMEN
Pantothenate kinase-associated neurodegeneration (PKAN) is a rare neurodegenerative condition. Major clinical features include progressive dystonia, pigmentary retinopathy, spasticity, and cognitive decline. The typical MRI sign of the disease, known as "eye-of-the-tiger", is what makes differential diagnosis possible. We here describe a 16-year-old male patient with PKAN presenting with severe and sustained jaw-opening dystonia which may be due to heterogeneous etiologies showing poor response to treatment. Herein, long-term follow-up and genetic results of a PKAN case who experienced severe jaw-opening dystonia are presented and discussed.
Asunto(s)
Neurodegeneración Asociada a Pantotenato Quinasa/genética , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , Adolescente , Adulto , Encéfalo/diagnóstico por imagen , Diagnóstico Diferencial , Estudios de Seguimiento , Humanos , Masculino , Movimiento/fisiología , Neurodegeneración Asociada a Pantotenato Quinasa/diagnóstico por imagen , Neurodegeneración Asociada a Pantotenato Quinasa/tratamiento farmacológico , Neurodegeneración Asociada a Pantotenato Quinasa/fisiopatología , Índice de Severidad de la Enfermedad , Grabación en Video , Adulto JovenRESUMEN
Rasmussen encephalitis is associated with severe seizures that are unresponsive to antiepileptic drugs, as well as immunosuppressants. Transcranial direct current stimulation (t-DCS) is a non-invasive and safe method tried mostly for focal epilepsies with different aetiologies. To date, there is only one published study with two case reports describing the effect of t-DCS in Rasmussen encephalitis. Our aim was to investigate the effect of t-DCS on seizures in Rasmussen encephalitis and to clarify its safety. Five patients (mean age: 19; three females), diagnosed with Rasmussen encephalitis were included in this study. Patients received first cathodal, then anodal (2 mA for 30 minutes on three consecutive days for non-sham stimulations), and finally sham stimulation with two-month intervals, respectively. Three patients received classic (DC) cathodal t-DCS whereas two patients received cathodal stimulation with amplitude modulation at 12 Hz. Afterwards, all patients received anodal stimulation with amplitude modulation at 12 Hz. In the last part of the trial, sham stimulation (a 60-second stimulation with gradually decreasing amplitude to zero in the last 15 seconds) was applied to three patients. Maximum current density was 571 mA/m2 using 70 mm x 50 mm wet sponge electrodes with 2-mA maximum, current controlled stimulator, and maximum charge density was 1028 C/m2 for a 30-minute stimulation period. After cathodal stimulation, all but one patient had a greater than 50% decrease in seizure frequency. Two patients who received modulated cathodal t-DCS had better results. The longest positive effect lasted for one month. A second trial with modulated anodal stimulation and a third with sham stimulation were not effective. No adverse effect was reported with all types of stimulations. Both classic and modulated cathodal t-DCS may be suitable alternative methods for improving seizure outcome in Rasmussen encephalitis patients.