Clinical variability of early-onset congenital myasthenic syndrome due to biallelic RAPSN mutations in Brazil.

Mutations in RAPSN are an important cause of congenital myasthenic syndrome (CMS), leading to endplate acetylcholine receptor deficiency. We present three RAPSN early-onset CMS patients (from a Brazilian cohort of 61 CMS patients). Patient 1 and patient 2 harbor the mutation p.N88K in homozygosity, while patient 3 harbors p.N88K in compound heterozygosity with another pathogenic variant (p.V165M; c.493G ≥ A). At onset, patient 3 presented with more severe symptoms compared to the other two, showing generalized weakness and repeated episodes of respiratory failure in the first years of life. During adolescence, she became gradually less symptomatic and does not require medication anymore, presenting better long-term outcomes than patients 1 and 2. This case series illustrates the variability of RAPSN early-onset CMS, with patient 3, despite severe onset, revealing an almost complete reversal of myasthenic symptoms, not limited to apneic episodes. Moreover, it suggests that RAPSN CMS may be underdiagnosed in non-European countries.

A common CHRNE mutation in Brazilian patients with congenital myasthenic syndrome.

The most common causes of congenital myasthenic syndromes (CMS) are CHRNE mutations, and some pathogenic allelic variants in this gene are especially frequent in certain ethnic groups. In the southern region of Brazil, a study found the c.130dupG CHRNE mutation in up to 33% of families with CMS. Here, we aimed to verify the frequency of this mutation among individuals with CMS in a larger cohort of CMS patients from different areas of Brazil and to characterize clinical features of these patients. Eighty-four patients with CMS, from 72 families, were clinically evaluated and submitted to direct sequencing of the exon 2 of CHRNE. The c.130dupG mutation was found in 32 patients (23 families), with 26 patients (19 families, 26.3%) in homozygosis, confirming its high prevalence in different regions of Brazil. Among the homozygous patients, the following characteristics were frequent: onset of symptoms before 2 years of age (92.3%), little functional restriction (92.3%), fluctuating symptoms (100%), ocular muscle impairment (96.1%), ptosis (100%), limb weakness (88.4%), response to pyridostigmine (100%), facial involvement (77%), and bulbar symptoms (70.8%). The pretest probability of finding at least one allele harbouring the c.130dupG mutation was 38.1%. Selecting only patients with impaired eye movement together with limb weakness and improvement with pyridostigmine, the probability increases to 72.2%. This clinical pre-selection of patients is likely a useful tool for regions where CHRNE mutations have a founder effect. In conclusion, the CHRNE mutation c.130dupG leads to fairly benign natural course of the disease with relative homogeneity.

Effects of structural integration Rolfing® method and acupuncture on fibromyalgia / Efeitos do método Rolfing® de integração estrutural e da acupuntura na fibromialgia

ABSTRACT BACKGROUND AND OBJECTIVES: Considering that a single approach does not encompass all symptoms of fibromyalgia syndrome and so indicated therapy is multidisciplinary, this study aimed at observing the efficacy of Structural Integration Rolfing method, of acupuncture, and of the combination of both techniques for relieving pain, anxiety and depression and for improving quality of life of fibromyalgia patients. METHODS: Participated in the study sixty patients of the Multidisciplinary Pain Center, Neurological Clinic, Clinicas Hospital, School of Medicine, University of São Paulo, who were randomly distributed in three groups: group A – submitted to 10 acupuncture sessions; group B – 10 Rolfing sessions; and group C – 10 Rolfing and 10 acupuncture sessions. All patients have maintained their routine outpatient treatment and were evaluated according to Fibromyalgia Impact Questionnaire, Pain Numeric Verbal Scale and Beck Anxiety and Depression Inventories, applied during initial interview, after the last session and three months after treatment completion. RESULTS: There has been statistically significant improvement in the three groups with regard to all evaluated items. CONCLUSION: Both techniques, individually or in association, were beneficial during the three months of follow up. .

RESUMO JUSTIFICATIVA E OBJETIVOS: Considerando-se que um único tratamento não abrange todos os sintomas apresentados no quadro da síndrome fibromiálgica e que, portanto, a conduta terapêutica indicada é multidisciplinar, o objetivo deste estudo foi verificar a eficácia do método Rolfing de Integração Estrutural, da acupuntura e da combinação das duas técnicas no alívio da dor, nos estados de ansiedade e depressão e na melhora da qualidade de vida dos fibromiálgicos. MÉTODOS: Sessenta pacientes do Centro Multidisciplinar de Dor da Clínica Neurológica do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo foram randomizados em três grupos: grupo A: submetidos a 10 sessões de acupuntura, grupo B 10 sessões de Rolfing e grupo C 10 sessões de Rolfing e 10 de acupuntura. Todos mantiveram o tratamento ambulatorial de rotina e foram avaliados de acordo com o Questionário de Impacto da Fibromialgia, a Escala Verbal Numérica de Dor e os Inventários de Ansiedade e de Depressão Beck, aplicados durante a entrevista inicial, após a última sessão e três meses após o término do tratamento. RESULTADOS: Houve melhora estatisticamente significativa nos pacientes dos três grupos em relação a todos os quesitos avaliados. CONCLUSÃO: As duas técnicas foram benéficas tanto individual quanto associadamente, durante os três meses de acompanhamento. .

Psychogenic non-epileptic seizures and psychoanalytical treatment: results / Crises não epilépticas psicogênicas e tratamento psicanalítico: resultados.

Background: the occurrence of psychogenic non-epileptic seizures (PNES) is estimated to be between 2 to 33 cases in every 100,000 inhabitants. The number of patients with PNES reaches 19% of those treated as epileptics. Patients with PNES are treated as if they had intractable epilepsy, with unsatisfactory results even after medication treatment is used to its maximum. The aim of this study is to present the effects of individual psychoanalytical treatment in patients with PNES, assessing its impact in the evolution of the clinical picture and its association with sex, time of disease, social, psychological and professional harm, as well as going through with treatment. Methods: The case base was composed of 37 patients with PNES. The diagnosis was reached with video-EEG monitoring. Psychoanalytical treatment was carried out through 12 months of weekly sessions timed for around 50-minutes each, in a total of 48 individual sessions. Results: This study found a high rate of success in the treatment of PNES patients. 29.7% (n=11) of patients had cessation or cure of symptoms and 51.4% (n=19) had a decrease in the number of episodes. There is an association between cessation or decrease in the number of episodes and sex (p<0.01), religion (p<0.01) and concluding treatment (p<0.01). Conclusion: Individual psychoanalytical treatment applied to patients with PNES is considered effective and can be an essential form of assistance for the reduction or cessation of episodes. .

Introdução: estima-se que o número de casos de pacientes com crises não epilépticas psicogênicas (CNEP) seja de 2 a 33 por 100 mil habitantes. O índice de CNEP corresponde ainda a, aproximadamente, 19% dos pacientes tratados como epilépticos. Os pacientes com CNEP são tratados como portadores de epilepsia refratária, chegando ao limite máximo do tratamento medicamentoso e sem a obtenção de resultados satisfatórios. Objetivo: relatar os efeitos do tratamento psicanalítico individual em pacientes com CNEP de forma a avaliar a evolução do quadro clínico de CNEP e verificar sua associação com gênero, tempo de crise, prejuízos sociais, afetivos e profissionais, bem como término do tratamento. Métodos: a casuística foi composta por 37 pacientes com diagnóstico de CNEP feito por meio da monitoração por vídeo-EEG. Foram realizadas sessões de tratamento psicanalítico: atendimento clínico individual com frequência semanal, com duração aproximada de 50 minutos e duração total de 48 sessões em 12 meses. Resultados: este estudo constatou elevado índice de sucesso no tratamento dos pacientes com CNEP: 29,7% (n = 11) de cessação/cura dos sintomas e 51,4% (n = 19) de redução das crises convulsivas. Foi constatada associação entre cessar ou reduzir as crises e gênero (p<0,01), religião (p<0,01) e término do tratamento (p<0,01). Conclusão: este estudo apontou eficácia do tratamento psicanalítico individual realizado com pacientes com CNEP, podendo ser considerada uma forma de assistência essencial para que haja decréscimo ou cessação das crises. .

Existence of a potential neurogenic system in the adult human brain.

BACKGROUND: Prevailingly, adult mammalian neurogenesis is thought to occur in discrete, separate locations known as neurogenic niches that are best characterized in the subgranular zone (SGZ) of the dentate gyrus and in the subventricular zone (SVZ). The existence of adult human neurogenic niches is controversial. METHODS: The existence of neurogenic niches was investigated with neurogenesis marker immunostaining in histologically normal human brains obtained from autopsies. Twenty-eight adult temporal lobes, specimens from limbic structures and the hypothalamus of one newborn and one adult were examined. RESULTS: The neural stem cell marker nestin stained circumventricular organ cells and the immature neuronal marker doublecortin (DCX) stained hypothalamic and limbic structures adjacent to circumventricular organs; both markers stained a continuous structure running from the hypothalamus to the hippocampus. The cell proliferation marker Ki-67 was detected predominantly in structures that form the septo-hypothalamic continuum. Nestin-expressing cells were located in the fimbria-fornix at the insertion of the choroid plexus; ependymal cells in this structure expressed the putative neural stem cell marker CD133. From the choroidal fissure in the temporal lobe, a nestin-positive cell layer spread throughout the SVZ and subpial zone. In the subpial zone, a branch of this layer reached the hippocampal sulcus and ended in the SGZ (principally in the newborn) and in the subiculum (principally in the adults). Another branch of the nestin-positive cell layer in the subpial zone returned to the optic chiasm. DCX staining was detected in the periventricular and middle hypothalamus and more densely from the mammillary body to the subiculum through the fimbria-fornix, thus running through the principal neuronal pathway from the hippocampus to the hypothalamus. The column of the fornix forms part of this pathway and appears to coincide with the zone previously identified as the human rostral migratory stream. Partial co-labeling with DCX and the neuronal marker ßIII-tubulin was also observed. CONCLUSIONS: Collectively, these findings suggest the existence of an adult human neurogenic system that rises from the circumventricular organs and follows, at minimum, the circuitry of the hypothalamus and limbic system.

Serial and prolonged EEG monitoring in anti-N-Methyl-d-Aspartate receptor encephalitis.

OBJECTIVE: To describe serial electroencephalographic (EEG) findings of three patients with anti-NMDAR encephalitis. METHODS: Three women (age 15-34years) with confirmed anti-NMDAR encephalitis underwent serial EEG recordings. Continuous EEG for 72h was performed in one case and 3-day video-EEG monitoring was obtained in two cases. RESULTS: Generalized rhythmic delta activity (GRDA) was found in all patients. GRDA persisted for hours, but was not continuous on a 24-h EEG recording, disclosed no frequency, voltage or field evolution, and was not seen on the first EEG of two patients. Extreme delta brush was noted in two patients who presented more severe disease. One patient presented seizures, which were electrographically and clinically different from the GRDA pattern and from dyskinetic movements. CONCLUSIONS: Serial or continuous EEG may be necessary to detect GRDA in anti-NMDAR patients. To avoid unnecessary treatment, this pattern should not be interpreted as indicative of ictal activity, unless there is evidence of its ictal nature. SIGNIFICANCE: Our findings may contribute to the diagnosis of anti-NMDAR encephalitis in cases with characteristic clinical picture.

Psychogenic non-epileptic seizures and psychoanalytical treatment: results.

BACKGROUND: the occurrence of psychogenic non-epileptic seizures (PNES) is estimated to be between 2 to 33 cases in every 100,000 inhabitants. The number of patients with PNES reaches 19% of those treated as epileptics. Patients with PNES are treated as if they had intractable epilepsy, with unsatisfactory results even after medication treatment is used to its maximum. The aim of this study is to present the effects of individual psychoanalytical treatment in patients with PNES, assessing its impact in the evolution of the clinical picture and its association with sex, time of disease, social, psychological and professional harm, as well as going through with treatment. METHODS: The case base was composed of 37 patients with PNES. The diagnosis was reached with video-EEG monitoring. Psychoanalytical treatment was carried out through 12 months of weekly sessions timed for around 50-minutes each, in a total of 48 individual sessions. RESULTS: This study found a high rate of success in the treatment of PNES patients. 29.7% (n=11) of patients had cessation or cure of symptoms and 51.4% (n=19) had a decrease in the number of episodes. There is an association between cessation or decrease in the number of episodes and sex (p<0.01), religion (p<0.01) and concluding treatment (p<0.01). CONCLUSION: Individual psychoanalytical treatment applied to patients with PNES is considered effective and can be an essential form of assistance for the reduction or cessation of episodes.

Unilateral central retinal artery occlusion as the sole presenting sign of Susac syndrome in a young man: case report.

We report the case of a 24-year-old man presenting with sudden visual loss in the left eye from a central retinal artery occlusion. An extensive clinical investigation revealed no etiology. Three weeks later, however, the patient developed hearing loss followed by encephalopathy and multiple branch retinal artery occlusions in the right eye. Fluorescein angiography confirmed retinal vascular occlusions with no sign of vasculitis. The neurological examination revealed a diffuse encephalopathy while the MRI scan disclosed several small areas of infarcts in the brain. Bilateral sensorineural hearing loss was confirmed on audiometry. The patient was diagnosed with Susac syndrome and treated with methylprednisolone and cyclophosphamide, resulting in slight improvement and stabilization. This case shows that Susac syndrome may be diagnosed late due to the absence at onset of one or more of the symptoms of the classic triad (encephalopathy, multiple branch retinal artery occlusions and hearing loss). This case also serves to emphasize that Susac syndrome should be considered in the differential diagnosis of central retinal artery occlusion, even in apparently healthy young men.

Unilateral central retinal artery occlusion as the sole presenting sign of Susac syndrome in a young man: case report / Oclusão unilateral da artéria central da retina como único sinal de apresentação da síndrome de Susac em jovem do sexo masculino: relato de caso

We report the case of a 24-year-old man presenting with sudden visual loss in the left eye from a central retinal artery occlusion. An extensive clinical investigation revealed no etiology. Three weeks later, however, the patient developed hearing loss followed by encephalopathy and multiple branch retinal artery occlusions in the right eye. Fluorescein angiography confirmed retinal vascular occlusions with no sign of vasculitis. The neurological examination revealed a diffuse encephalopathy while the MRI scan disclosed several small areas of infarcts in the brain. Bilateral sensorineural hearing loss was confirmed on audiometry. The patient was diagnosed with Susac syndrome and treated with methylprednisolone and cyclophosphamide, resulting in slight improvement and stabilization. This case shows that Susac syndrome may be diagnosed late due to the absence at onset of one or more of the symptoms of the classic triad (encephalopathy, multiple branch retinal artery occlusions and hearing loss). This case also serves to emphasize that Susac syndrome should be considered in the differential diagnosis of central retinal artery occlusion, even in apparently healthy young men.

Descrevemos um paciente de 24 anos, sexo masculino, que se apresentou com perda súbita da visão do olho esquerdo causado por oclusão da artéria central da retina. Ele foi submetido à investigação clínica detalhada sem encontrar uma causa. Três semanas depois, no entanto, desenvolveu surdez, encefalopatia e múltiplas oclusões de ramo arterial da retina no olho direito. Angiofluoresceinografia confirmou as oclusões de ramo arterial no OD e oclusão da artéria central da retina no OE, sem qualquer sinal de vascutile. O exame neurológico revelou encefalopatia difusa, enquanto que o estudo efetuado por ressonância nuclear magnética mostrou várias áreas de enfarte do cérebro e a audiometria demonstrou perda auditiva neurosensorial bilateral. A síndrome de Susac foi diagnosticada e tratamento com metilprednisolona e ciclofosfamida instituido com melhora discreta, seguida de estabilização clínica. Este caso é importante para chamar a atenção de que nem todos os três critérios diagnósticos (encefalopatia, oclusão de ramo arterial retiniano e surdez) para a síndrome de Susac precisam estar presentes de início, o que pode causar confusão diagnóstica. O diagnóstico deve portanto ser incluído no diferencial de oclusão da artéria central da retina mesmo quando ocorre em homem sem outros sintomas associados.

Cerebral Embolic Activity in a Patient during Acute Crisis of Takayasu's Arteritis.

Takayasu's arteritis is a disease that affects large vessels and may cause neurological symptoms either by stenoses/occlusions or embolisms from vessels with an inflammatory process. Transcranial Doppler (TCD) ultrasound can provide useful information for diagnosis and monitoring during the active phase of the disease. Cerebral embolic signals can be detected by TCD and have been considered a risk factor for vascular events. We report a patient in whom TCD ultrasound was used to monitor cerebral embolic signals during the active phase of the disease. This case report suggests that embolic activity in Takayasu's arteritis may represent disease activity, and its monitoring may be useful for evaluating the response to therapy.

Multiple endocrine neoplasia type 1 presenting as refractory epilepsy and polyneuropathy--a case report.

Hypoglycemia is a well recognized cause of acute symptomatic seizures. The fact that hypoglycemia can cause peripheral neuropathy is less appreciated. We describe a case of insulinoma associated peripheral neuropathy. A 17 year-old previously healthy man was referred for investigation of refractory epilepsy. A history of recurrent seizures, slowly progressive weakness of his feet and hands, and weight gain was obtained. Physical examination showed signs of a chronic sensory-motor polyneuropathy. He was diagnosed with insulinoma and primary hyperparathyroidism, characterizing multiple endocrine neoplasia, type 1 syndrome. Cases of insulinoma associated peripheral neuropathy are very rare. The more characteristic clinical picture appears to be distal weakness, worse in the intrinsic hand and feet muscles, and no or mild sensory signs. Peripheral nervous system symptoms may not completely resolve, despite removal of the cause of hyperinsulinism/hypoglycemia and full reversion of central nervous system symptoms. Mechanisms underlying hypoglycemic neuropathy are still poorly understood.

Cor pulmonale in a patient with Brown-Vialetto-Van Laere syndrome: a case report.

Brown-Vialetto-Van Laere syndrome (BVVLS) is a rare neurological disease characterized by sensorineural hearing loss and multiple cranial nerve palsies, usually involving the VIIth and IXth to XIIth cranial nerves. We describe the clinical and pathological features of a 33-year-old woman with BVVLS. The patient developed progressive exertional dyspnea, with clinical and laboratory findings of right-sided heart failure and pulmonary hypertension. She developed status epilepticus in the setting of cardiac deterioration and respiratory infection, and died of cardiogenic and septic shock. Autopsy disclosed bilateral neuronal loss and gliosis in the inferior colliculi, locus coeruleus and facial and vestibular nuclei. Cor pulmonale is a complication of hypoventilation-induced hypoxia and hypercapnia and had not yet been reported in BVVLS.

Interhemispheric asymmetry of corticomotor excitability after chronic cerebellar infarcts.

Early after stroke, there is loss of intracortical facilitation (ICF) and increase in short-interval intracortical inhibition (SICI) in the primary motor cortex (M1) contralateral to a cerebellar infarct. Our goal was to investigate intracortical M1 function in the chronic stage following cerebellar infarcts (>4 months). We measured resting motor threshold (rMT), SICI, ICF, and ratios between motor-evoked potential amplitudes (MEP) and supramaximal M response amplitudes (MEP/M; %), after transcranial magnetic stimulation was applied to the M1 contralateral (M1(contralesional)) and ipsilateral (M1(ipsilesional)) to the cerebellar infarct in patients and to both M1s of healthy age-matched volunteers. SICI was decreased in M1(contralesional) compared to M1(ipsilesional) in the patient group in the absence of side-to-side differences in controls. There were no significant interhemispheric or between-group differences in rMT, ICF, or MEP/M (%). Our results document disinhibition of M1(contralesional) in the chronic phase after cerebellar stroke.