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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 Espinocerebelares , Degenerações Espinocerebelares , Humanos , Espasticidade Muscular , Turquia/epidemiologiaRESUMO
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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Autoanticorpos/sangue , Epilepsia/sangue , Epilepsia/tratamento farmacológico , Imunoglobulinas Intravenosas/uso terapêutico , Receptores de Glicina/sangue , Adulto , Biomarcadores/sangue , Epilepsia Resistente a Medicamentos/sangue , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Epilepsia Resistente a Medicamentos/fisiopatologia , Eletroencefalografia/métodos , Epilepsias Parciais/sangue , Epilepsias Parciais/tratamento farmacológico , Epilepsias Parciais/fisiopatologia , Epilepsia/fisiopatologia , Epilepsia do Lobo Temporal/sangue , Epilepsia do Lobo Temporal/tratamento farmacológico , Epilepsia do Lobo Temporal/fisiopatologia , Feminino , Seguimentos , Células HEK293 , Humanos , Masculino , Pessoa de Meia-Idade , Estado Epiléptico/sangue , Estado Epiléptico/tratamento farmacológico , Estado Epiléptico/fisiopatologia , Adulto JovemRESUMO
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/etiologia , Esclerose Tuberosa/complicações , Criança , Humanos , Masculino , Estado Epiléptico/diagnósticoRESUMO
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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Doença de Charcot-Marie-Tooth/genética , Ataque Isquêmico Transitório , Acidente Vascular Cerebral , Adolescente , Conexinas , Humanos , Ataque Isquêmico Transitório/genética , Masculino , MutaçãoRESUMO
Cytochrome c oxidase (COX) deficiency is a frequent biochemical abnormality in mitochondrial disorders, but a large fraction of cases remains genetically undetermined. Whole-exome sequencing led to the identification of APOPT1 mutations in two Italian sisters and in a third Turkish individual presenting severe COX deficiency. All three subjects presented a distinctive brain MRI pattern characterized by cavitating leukodystrophy, predominantly in the posterior region of the cerebral hemispheres. We then found APOPT1 mutations in three additional unrelated children, selected on the basis of these particular MRI features. All identified mutations predicted the synthesis of severely damaged protein variants. The clinical features of the six subjects varied widely from acute neurometabolic decompensation in late infancy to subtle neurological signs, which appeared in adolescence; all presented a chronic, long-surviving clinical course. We showed that APOPT1 is targeted to and localized within mitochondria by an N-terminal mitochondrial targeting sequence that is eventually cleaved off from the mature protein. We then showed that APOPT1 is virtually absent in fibroblasts cultured in standard conditions, but its levels increase by inhibiting the proteasome or after oxidative challenge. Mutant fibroblasts showed reduced amount of COX holocomplex and higher levels of reactive oxygen species, which both shifted toward control values by expressing a recombinant, wild-type APOPT1 cDNA. The shRNA-mediated knockdown of APOPT1 in myoblasts and fibroblasts caused dramatic decrease in cell viability. APOPT1 mutations are responsible for infantile or childhood-onset mitochondrial disease, hallmarked by the combination of profound COX deficiency with a distinctive neuroimaging presentation.
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Proteínas Reguladoras de Apoptose/genética , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Leucoencefalopatias/genética , Leucoencefalopatias/patologia , Proteínas Mitocondriais/genética , Mutação/genética , Adolescente , Adulto , Células Cultivadas , Criança , Pré-Escolar , Deficiência de Citocromo-c Oxidase , Complexo IV da Cadeia de Transporte de Elétrons/genética , Feminino , Fibroblastos/metabolismo , Fibroblastos/patologia , Humanos , Lactente , Leucoencefalopatias/enzimologia , Imageamento por Ressonância Magnética , Masculino , Mitocôndrias/metabolismo , Mioblastos/metabolismo , Mioblastos/patologiaRESUMO
BACKGROUND AND PURPOSE: Burning mouth syndrome is a chronic and persistent painful condition characterized by burning sensation in the oral mucosa. We investigated the etiological factors of patients presented with the history of burning in the mouth who admitted our outpatient clinics over the 8-years period and who had no underlying identifiable local factors. We also tried to determine their demographic and clinical characteristics. Our aim was to investigate the association between burning mouth and psychiatric disorders such as depression and anxiety, chronic diseases like diabetes mellitus (DM) and other laboratory studies in patients complaining of solely burning in the mouth. METHODS: The study included patients with the history of burning in mouth who presented in our outpatient clinic between 2005 and 2012. They were evaluated by a neurologist, a psychiatrist, an internist, and a dentist. Complete blood counts, biochemical analysis and cranial magnetic resonance imaging (MRI) were performed for all patients. RESULTS: A total of 26 (22 (84%) females, 4 (15%) males; mean age 55.9 years) patients were enrolled in this study. Five (19.2%) of the patients had depression, 2 (7.7%) had anxiety disorder, 2 (7.7%) had diabetes mellitus, 8 (30%) had B12 vitamin deficiency, 3 (11.5%) had decreased ferritin levels in blood, and 1 (3.8%) had folic acid deficiency. Cranial MRI of all patients were normal. Nine patients (34.6%) had no etiological causes. CONCLUSION: A multidisciplinary approach in the management of burning mouth and establishment of common criteria for the diagnosis would provide insight into the underlying pathophysiological mechanism.
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Síndrome da Ardência Bucal/diagnóstico , Síndrome da Ardência Bucal/etiologia , Adulto , Idoso , Ansiedade/epidemiologia , Depressão/epidemiologia , Diabetes Mellitus/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Deficiência de Vitamina B 12/epidemiologiaRESUMO
OBJECTIVE: To examine the incidence of restless legs syndrome (RLS) among children with iron deficiency, or iron deficiency anemia, or both, and the relationship between RLS prevalence and serum ferritin levels. METHODS: This prospective, cross-sectional, case controlled study was carried out between January and June 2013, and included 98 iron deficiency and/or iron deficiency anemia, and 102 healthy children referred to the Neurology and Pediatric Departments of the Medical Faculty of Bezmialem Vakif University, Istanbul, Turkey. Both groups were evaluated according to the International Restless Legs Syndrome Study Group diagnostic criteria. RESULTS: The range of ferritin levels was 0.01-12 mg/ml in patients while it was 12.3-91.8 mg/mL in the control group. Restless legs syndrome was detected in 61.2% of children with iron deficiency anemia, and in 37.3% of children with normal biochemistry values. A statistically significant correlation was found between serum ferritin levels and frequency of RLS. In patients with serum ferritin levels higher than 50 ng/ml, 92.3% had no RLS, while 55.2% of patients with serum ferritin levels lower than 50 ng/ml had RLS. The patients with serum ferritin levels of > 50 ng/ml had a significantly higher incidence of RLS. Serum ferritin levels were significantly different between the 2 groups. CONCLUSION: The incidence of RLS, also known as Willis-Ekbom Disease, is high in children aged between 8-18 years with iron deficiency, or iron deficiency anemia, or both. This finding supports the importance of iron replacement therapy especially during the growth and development of children.
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Anemia Ferropriva/complicações , Ferritinas/sangue , Síndrome das Pernas Inquietas/sangue , Síndrome das Pernas Inquietas/epidemiologia , Adolescente , Estudos de Casos e Controles , Criança , Estudos Transversais , Feminino , Humanos , Imunoensaio , Incidência , Medições Luminescentes , Masculino , Estudos Prospectivos , Turquia/epidemiologiaRESUMO
Autoimmunity has aroused interest in the last years as a contributory mechanism of epilepsy, especially in epilepsies with unknown cause or therapy resistance. Since the relationship of absence epilepsy (AE) with calcium channels is well established, we aimed to investigate related antibodies in patients diagnosed with AE. Consecutive patients with typical absence seizures having either childhood absence epilepsy (CAE) or juvenile absence epilepsy (JAE) with generalized spike and wave discharges on electroencephalography (EEG) were included after their consent. The patients were diagnosed according to the International League Against Epilepsy (ILAE) 2010 criteria. Antibodies against P-Q type voltage gated calcium channels (VGCC) and T-type VGCC subunit Cav3.2 (encoded by the CACNA1H gene) were investigated by RIA and ELISA, respectively. We searched for these antibodies in 32 patients with AE and 53 patients with focal epilepsy of unknown cause (FEOUC) as the disease control group; furthermore, 30 healthy persons served as the healthy controls. Eleven patients (34.3%) with AE had CAE and the remaining patients had JAE. Only a 47-year-old female FEOUC patient, who also had systemic lupus erythematosus with normal MRI scans showed antibodies against P-Q type VGCC, whereas no antibody positivity could be found in other FEOUC and AE patients and healthy controls. Our results might suggest that calcium channel antibodies do not play an important role in the pathophysiology of AE. Further studies with larger groups of other epileptic syndromes are needed to confirm our results.
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Autoanticorpos/sangue , Canais de Cálcio/imunologia , Epilepsia Tipo Ausência/imunologia , Adolescente , Adulto , Criança , Epilepsia Tipo Ausência/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
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 , Espectrometria de Massas em Tandem , Animais , Autoanticorpos , Cromatografia Líquida , Células HEK293 , Humanos , Imunoglobulina G , RatosRESUMO
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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Autoanticorpos/sangue , Epilepsia/diagnóstico , Epilepsia/imunologia , Proteínas de Membrana/imunologia , Neurônios/imunologia , Receptores de Neurotransmissores/imunologia , Adolescente , Adulto , Criança , Pré-Escolar , Epilepsia/sangue , Feminino , Seguimentos , Humanos , Lactente , Síndrome de Lennox-Gastaut/diagnóstico , Síndrome de Lennox-Gastaut/imunologia , Masculino , Espasmos Infantis/diagnóstico , Espasmos Infantis/imunologia , Adulto JovemRESUMO
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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Cistos , Doenças Desmielinizantes Hereditárias do Sistema Nervoso Central , Proteínas de Membrana/genética , Mutação/genética , Proteínas/genética , Adolescente , Proteínas de Ciclo Celular , Córtex Cerebral/diagnóstico por imagem , Criança , Pré-Escolar , Estudos Transversais , Cistos/diagnóstico por imagem , Cistos/genética , Cistos/fisiopatologia , Feminino , Doenças Desmielinizantes Hereditárias do Sistema Nervoso Central/diagnóstico por imagem , Doenças Desmielinizantes Hereditárias do Sistema Nervoso Central/genética , Doenças Desmielinizantes Hereditárias do Sistema Nervoso Central/fisiopatologia , Humanos , Cooperação Internacional , Imageamento por Ressonância Magnética , Masculino , Estudos Retrospectivos , Índice de Gravidade de Doença , Adulto JovemRESUMO
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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Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno Autístico/tratamento farmacológico , Everolimo/uso terapêutico , Imunossupressores/uso terapêutico , Esclerose Tuberosa , Adolescente , Epilepsia/tratamento farmacológico , Everolimo/efeitos adversos , Feminino , Humanos , Imunossupressores/efeitos adversos , MasculinoRESUMO
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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Autoanticorpos/sangue , Epilepsia/complicações , Epilepsia/imunologia , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/imunologia , Adulto , Animais , Biomarcadores/sangue , Encéfalo/diagnóstico por imagem , Encéfalo/imunologia , Encéfalo/patologia , Células Cultivadas , Epilepsia/sangue , Epilepsia/patologia , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Neurônios/imunologia , Neurônios/patologia , Ratos , Estudos RetrospectivosRESUMO
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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Neurodegeneração Associada a Pantotenato-Quinase/genética , Neurodegeneração Associada a Pantotenato-Quinase/fisiopatologia , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Idade de Início , Progressão da Doença , Distonia/etiologia , Transtornos Neurológicos da Marcha/etiologia , Humanos , Neurodegeneração Associada a Pantotenato-Quinase/complicações , Linhagem , TurquiaRESUMO
This study evaluated the EEG findings of patients whose seizures were associated with a possible autoimmune etiology. Our aim was to find clues to distinguish patients with antineuronal antibodies (Ab) through EEG studies. We reviewed our database and identified antineuronal Ab positive epilepsy patients with or without autoimmune encephalitis. These patients had Abs to N-methyl-d-aspartate receptor (NMDAR) (n = 5), glycine receptor (GLY-R) (n = 5), contactin-associated protein-like 2 (CASPR-2) (n = 4), uncharacterized voltage-gated potassium channel complex (VGKC) antigens (n = 2), glutamic acid decarboxylase (GAD) (n = 2), Hu (n = 1), and amphiphysin (n = 1). The control group consisted of 21 seronegative epilepsy or encephalopathy patients with similar clinical features. EEG findings were compared between the groups in a blindfolded design. We did not find any significant difference in EEG findings between antineuronal Ab positive epilepsy patients and seronegative control group. It was remarkable that four seropositive but none of the seronegative patients presented with nonconvulsive status epilepticus (NCSE) or focal motor status epilepticus. Continuous theta and delta rhythms were observed in 5 (71%) seropositive patients with autoimmune encephalitis and 2 (25%) seronegative patients. Eight (40 %) seropositive patients showed a frontal intermittent rhythmic delta activity (FIRDA) pattern as opposed to 5 (24%) seronegative patients. Two patients with NMDAR Ab positivity showed rhythmic delta waves superimposed with beta frequency activity resembling "delta brush" pattern. EEG seems as a limited diagnostic tool in differentiating epilepsy and/or encephalopathy patients with a possible autoimmune etiology from those without. However, antineuronal Abs associated with encephalitis should be considered in the etiology of status epilepticus forms. A possible autoimmune etiology for seizures may be considered in the presence of continuous slow waves, FIRDA, and delta brush pattern in the EEG.
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Autoanticorpos/imunologia , Eletroencefalografia/métodos , Encefalite/diagnóstico , Encefalite/imunologia , Epilepsia/diagnóstico por imagem , Epilepsia/imunologia , Doença de Hashimoto/diagnóstico , Doença de Hashimoto/imunologia , Adulto , Idoso , Encéfalo/imunologia , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto JovemRESUMO
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.
Assuntos
Autoanticorpos , Córtex Cerebral/imunologia , Encefalite/imunologia , Epilepsia Parcial Contínua/imunologia , Neurônios/imunologia , Adolescente , Atrofia/diagnóstico por imagem , Atrofia/imunologia , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/patologia , Criança , Pré-Escolar , Encefalite/diagnóstico por imagem , Encefalite/patologia , Epilepsia Parcial Contínua/diagnóstico por imagem , Epilepsia Parcial Contínua/patologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Neurônios/patologia , Testes Neuropsicológicos , Adulto JovemRESUMO
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.
Assuntos
Neurodegeneração Associada a Pantotenato-Quinase/genética , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Adolescente , Adulto , Encéfalo/diagnóstico por imagem , Diagnóstico Diferencial , Seguimentos , Humanos , Masculino , Movimento/fisiologia , Neurodegeneração Associada a Pantotenato-Quinase/diagnóstico por imagem , Neurodegeneração Associada a Pantotenato-Quinase/tratamento farmacológico , Neurodegeneração Associada a Pantotenato-Quinase/fisiopatologia , Índice de Gravidade de Doença , Gravação em Vídeo , Adulto JovemRESUMO
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.