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Introdução. A forma autossômica dominante de miopatia centronuclear devido a mutações no gene dinamina 2 pode ser de gravidade variável Objetivo. Caracterizar os achados clínicos e eletrodiagnósticos de uma família portadora da mutação da dinamina 2 (c.1393C>T, p.Arg465Trp). Método. Estudo descritivo, realizado no Hospital Universitario Walter Cantídio, Fortaleza, Ceará. Resultados. Paciente apresentou desenvolvimento normal até os 9 anos, quando progrediu para fraqueza nos membros, quedas frequentes e piora da marcha, confinada aos 42 anos a uma cadeira de rodas. A eletroneuromiografia mostrou padrão miopático. Conclusão. O caso evoluiu para um fenótipo grave, demonstrando a variabilidade clínica quanto a progressão dos sintomas.

Introduction. Alemtuzumab is a humanized monoclonal antibody against the CD52 antigen. It is a highly efficacious drug for the treatment of relapsing remitting multiple sclerosis (MS). The treatment protocol consists in 2 treatment cycles: 12mg/day i.v. infusions for 5 consecutive days and after one-year 12mg/day infusions for 3 days. To our knowledge, there is a single case series in the literature detailing MS remission after a single cycle of Alemtuzumab. Here, we report a similar experience. Case report. A 48-year-old woman with fluctuating right leg weakness for three years and burning pain in the right foot was diagnosed with MS. She was started on Betaferon©. Her condition progressed and in less than one year, she was switched to glatiramer and after new MS relapses to fingolimod. Disease progressed to Expanded Disability Status Scale (EDSS) of 7.0. She was started on Alemtuzumab (five-day course of 12mg i.v. on 6/2018). A second Alemtuzumab cycle was not given since she failed to follow monitoring guidelines. She had no signs of disease activity after four years. Conclusions. It is possible that MS remission may be achieved with a single cycle of Alemtuzumab.

TANK-binding kinase 1 (TBK1) gene mutations cause ALS and frontotemporal dementia (FTD). We report a novel TBK1 mutation in a Brazilian patient with ALS. Symptoms started at age 44 (lower-limb onset). Despite treatment with riluzole, his condition progressed over 5 years to aphemia, dysphagia, gastrostomy and tracheostomy. A diagnostic test panel for neurodegenerative disorders disclosed a novel likely pathogenic heterozygous intronic mutation in the TBK1 gene: c.1189 + 1G gt; T (Splice donor), intron 9. This mutation is expected to disrupt RNA splicing and lead to loss of protein function. Disruption of this splice site has been observed in patients with TBK1-related disorders. Separate and additional C9ORFF72 testing was negative. To our knowledge, this is the second patient with a TBK1 mutation (novel splice donor intronic mutation) reported in Brazil, and the first to include a full description of the clinical course. Further studies are necessary to establish the frequency of TBK1 mutations in Brazilian ALS patients (and worldwide) and to evaluate the possible different clinical phenotypes and the disease course.

CONTEXT: Spinal-generated movement disorders are a complex group of medical conditions, frequently misdiagnosed, originating in the spinal cord or from combined peripheral and central nervous system involvement. In this case report, we describe a novel form of position-dependent dyskinesia due to severe craniocervical malformation. FINDINGS: An 83-year-old woman with basilar invagination at the C2 vertebra above the line of Chamberlain, occipitocervical lordosis, platybasia with a short clivus, ankylosis of the C1–C2 complex and fusion of the C1 arch developed an unusual pattern of position-dependent left arm dyskinesia triggered by bending her neck forward with simultaneous contact of the flexed elbow with a flat surface. Symptoms did not improve with anticonvulsants and she progressed and died suddenly. CONCLUSION/CLINICAL RELEVANCE: A newly described form of position-dependent arm dyskinesia can be associated with severe craniocervical malformation.

A síndrome de Guillain–Barré (SGB) é uma doença imunomediada rara, mas potencialmente fatal, dos nervos periféricos e das raízes nervosas, que é geralmente desencadeada por infecções. A incidência da SGB pode, portanto, aumentar durante surtos de doenças infecciosas, como foi observado durante a epidemia do vírus Zika em 2013 na Polinésia Francesa e em 2015 na América Latina. O diagnóstico e manejo da SGB podem ser complicados visto que sua apresentação clínica e o curso da doença são heterogêneos e não existem atualmente diretrizes clínicas internacionais disponíveis. Para auxiliar os médicos, especialmente em um cenário de surto, desenvolvemos uma diretriz globalmente aplicável para o diagnóstico e manejo da SGB. A diretriz se baseia no consenso de especialistas e na literatura atual e tem uma estrutura de dez etapas para facilitar seu uso na prática clínica. Primeiro fornecemos uma introdução aos critérios diagnósticos, às variantes clínicas e aos diagnósticos diferenciais da SGB. A seguir, as dez etapas abrangem o reconhecimento e o diagnóstico precoces da SGB, a internação na unidade de terapia intensiva, a indicação e seleção do tratamento, o monitoramento e tratamento da progressão da doença, o prognóstico do curso e resultado clínico e o manejo das complicações e sequelas.

Peripheral neuropathies (PN) and primary headaches (PH) are common comorbidities in inflammatory bowel disease (IBD) patients. We aimed to evaluate whether PN and PH affect the same subgroups of IBD patients. Since 2004, we established a cohort study to evaluate neurological diseases in IBD patients. Over 2 years, all consecutive (N = 155) IBD patients (either Crohn’s disease (CD) or ulcerative colitis (UC) were evaluated for the presence of PN and PH. PH were also evaluated in dyspeptic patients (N = 84) and IBD relatives (controls, N = 101). After neurological evaluation, symptomatic patients underwent skin wrinkling test to evaluate small fiber function and/or electromyography. Headaches and migraine were more prevalent in IBD than control patients: 52.3 and 34.2% vs. 40.6 and 20.8% (P 0.05). Multivariate regression analysis disclosed that headaches were more prevalent in women, co-existing psychiatric disease, IBD, CD, and UC. After age, gender distribution, and prevalence of hypertension and psychiatric diseases were matched among the groups, there were still differences in the prevalence of headaches and migraine among IBD, CD, and UC versus control patients. In summary, PH and PN are common in IBD and do not affect the same subgroups of patients.

Background: Bleeding in hemophiliacs can cause complications in the central and peripheral nervous system (CNS and PNS). The incidence of intracranial hemorrhage has reduced after the introduction of prophylactic treatment with factor VIII or IX, but the benefits of this therapy have not yet been evaluated on PNS complications. Objective: The aim of this study was to determine the prevalence of neurological complications in hemophiliacs and verify the effect of prophylactic therapy in these patients, including PNS disorders. Methods: We retrospectively evaluated the prevalence of CNS and PNS disorders caused by bleeding in hemophiliacs seen at the Hemocentro Regional Norte, Ceará, Brazil, from 1992 to 2018, and we compared the incidence in different periods (before and after the introduction of prophylactic treatment in 2011). Results: Of 75 hemophilia A patients evaluated (4.61/100.000 population), 13.3% (n=10) had either CNS (n=5) or PNS (n=5) disorders secondary to bleeding. Patients submitted to factor VIII replacement prophylactic therapy were less likely to have CNS events: from 1992 to 2011, 5 of 63 patients had CNS disease, while from 2011 to 2018, there were no new cases (p=0.0181). From 2011 to 2018, 5 PNS events occurred in patients without prophylactic therapy, whereas none occurred in those covered by prophylactic therapy (5/20 versus 0/29, p=0.0081). Conclusions: The prevalence of neurological complications in hemophiliacs in our cohort is similar to other studies. Similar to CNS, prophylactic therapy also reduces the risk of PNS complications. This is the first report in the literature showing this benefit. RESUMO Antecedentes: O sangramento em hemofílicos causa complicações no sistema nervoso central e periférico (SNC e SNP). A incidência de hemorragia intracraniana diminuiu após a introdução da profilaxia com fator VIII ou IX, entretanto esse benefício ainda não foi avaliado no SNP. Objetivo: O objetivo deste estudo foi determinar a prevalência de complicações neurológicas em hemofílicos, verificando o efeito da terapia profilática também no SNP. Métodos: Avaliamos retrospectivamente a prevalência de complicações neurológicas causadas por sangramentos em hemofílicos atendidos no Hemocentro Regional Norte, Ceará, Brasil, de 1992 a 2018, comparando a incidência em diferentes períodos (antes e depois da introdução do tratamento profilático em 2011). Resultados: Foram avaliados 75 pacientes com hemofilia A (4,61/100 mil habitantes). Deles, 13,3% (n=10) tinham distúrbios do SNC (n=5) ou do SNP (n=5) secundários a hemorragias. Os pacientes submetidos à terapia profilática com fator VIII apresentaram menor probabilidade de eventos do SNC: de 1992 a 2011, cinco de 63 pacientes apresentaram hemorragia no SNC, enquanto de 2011 a 2018 não ocorreram novos casos (p=0,0181). De 2011 a 2018, cinco eventos no SNP ocorreram entre pacientes sem terapia profilática, e nenhum ocorreu entre aqueles cobertos pela profilaxia (5/20 × 0/29, p=0,0081). Conclusões: A prevalência de complicações neurológicas em hemofílicos em nossa coorte é similar à de outros estudos. Assim como no SNC, a terapia profilática também reduz o risco de complicações no SNP. Este é o primeiro relato na literatura a mostrar esse benefício.

The Scientific Department of Neuroimmunology of the Brazilian Academy of Neurology (DCNI/ABN) and Brazilian Committee for Treatment and Research in Multiple Sclerosis and Neuroimmunological Diseases (BCTRIMS) provide recommendations in this document for vaccination of the population with demyelinating diseases of the central nervous system (CNS) against infections in general and against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes COVID-19. We emphasize the seriousness of the current situation in view of the spread of COVID-19 in our country. Therefore, reference guides on vaccination for clinicians, patients, and public health authorities are particularly important to prevent some infectious diseases. The DCNI/ABN and BCTRIMS recommend that patients with CNS demyelinating diseases (e.g., MS and NMOSD) be continually monitored for updates to their vaccination schedule, especially at the beginning or before a change in treatment with a disease modifying drug (DMD). It is also important to note that vaccines are safe, and physicians should encourage their use in all patients. Clearly, special care should be taken when live attenuated viruses are involved. Finally, it is important for physicians to verify which DMD the patient is receiving and when the last dose was taken, as each drug may affect the induction of immune response differently.

Guillain-Barré syndrome (GBS) is a rare, but potentially fatal, immune-mediated disease of the peripheral nerves and nerve roots that is usually triggered by infections. The incidence of GBS can therefore increase during outbreaks of infectious diseases, as was seen during the Zika virus epidemics in 2013 in French Polynesia and in 2015 in Latin America. Diagnosis and management of GBS can be complicated as its clinical presentation and disease course are heterogeneous, and no international clinical guidelines are currently available. To support clinicians, especially in the context of an outbreak, we have developed a globally applicable guideline for the diagnosis and management of GBS. The guideline is based on current literature and expert consensus, and has a ten-step structure to facilitate its use in clinical practice. We first provide an introduction to the diagnostic criteria, clinical variants and differential diagnoses of GBS. The ten steps then cover early recognition and diagnosis of GBS, admission to the intensive care unit, treatment indication and selection, monitoring and treatment of disease progression, prediction of clinical course and outcome, and management of complications and sequelae.El síndrome de Guillain-Barré (SGB) es una enfermedad inmunológica del nervio periférico y las raíces nerviosas, poco frecuente, potencialmente mortal y que suele desencadenarse por infecciones. La incidencia del SGB puede aumentar durante el brote de enfermedades infecciosas, tal como se observó en las epidemias del virus Zika en la Polinesia Francesa en 2013 y en América Latina en 2015. El diagnóstico y el manejo clínico del SGB pueden ser complicados ya que su presentación y el curso de la enfermedad son heterogéneos, y actualmente no se cuenta con guías clínicas internacionales. Para respaldar a los médicos, especialmente en el contexto de un brote de una enfermedad infecciosa, hemos desarrollado una guía clínica aplicable en todo el mundo para el diagnóstico y el tratamiento del SGB. La guía se basa en literatura actualizada y el consenso de expertos, y tiene una estructura de diez pasos para facilitar su uso en la práctica clínica. Inicialmente, brindamos una introducción a los criterios de diagnóstico, variantes clínicas y diagnósticos diferenciales del SGB. Los diez pasos luego abordan el reconocimiento y el diagnóstico temprano del SGB, la admisión a la unidad de cuidados intensivos, indicación y selección de tratamiento, seguimiento y tratamiento de la progresión de la enfermedad, predicción del curso clínico, resultados y tratamiento de complicaciones y secuelas.

Guillain–Barré syndrome (GBS) is a rare, but potentially fatal, immune-mediated disease of the peripheral nerves and nerve roots that is usually triggered by infections. The incidence of GBS can therefore increase during outbreaks of infectious diseases, as was seen during the Zika virus epidemics in 2013 in French Polynesia and 2015 in Latin America. Diagnosis and management of GBS can be complicated as its clinical presentation and disease course are heterogeneous, and no international clinical guidelines are currently available. To support clinicians, especially in the context of an outbreak, we have developed a globally applicable guideline for the diagnosis and management of GBS. The guideline is based on current literature and expert consensus, and has a ten-step structure to facilitate its use in clinical practice. We first provide an introduction to the diagnostic criteria, clinical variants and differential diagnoses of GBS. The ten steps then cover early recognition and diagnosis of GBS, admission to the intensive care unit, treatment indication and selection, monitoring and treatment of disease progression, prediction of clinical course and outcome, and management of complications and sequelae., In this Consensus Statement, Leonhard et al. provide a globally applicable guideline for the diagnosis and management of Guillain–Barré syndrome, including information on early recognition of the disease, prediction of clinical course and outcome, and management of complications and sequelae., Key points Classic Guillain–Barré syndrome (GBS) is an acute-onset ascending sensorimotor neuropathy, but the disease can present atypically or as a clinical variant.Abnormal results in electrophysiological studies and a combination of an increased protein level and normal cell count in cerebrospinal fluid are classic features of GBS, but patients with GBS can have normal results in both tests, especially early in the disease course.Respiratory function should be monitored in all patients as respiratory failure can occur without symptoms of dyspnoea.Intravenous immunoglobulin and plasma exchange are equally effective in treating GBS; no other treatments have been proven to be effective.The efficacy of repeat treatment in patients who have shown insufficient clinical response is uncertain; nevertheless, this practice is common in patients who show deterioration after an initial treatment response.Clinical improvement is usually most extensive in the first year after disease onset and can continue for >5 years.

The Zika virus (ZIKV) epidemic in Brazil in 2015‐2016 was followed by an increase in the incidence of patients with Guillain‐Barré syndrome (GBS). With this national survey study, we aimed to gain a better understanding of how neurologists in Brazil are currently diagnosing and treating patients with GBS, and how this increase in incidence has impacted the management of the disease. The questionnaire consisted of 52 questions covering: personal profile of the neurologist, practice of managing GBS during and outside of the ZIKV epidemic, and limitations in managing GBS. All 3264 neurologists that were member of the Brazilian Academy of Neurology at the time of the study were invited to participate. The questionnaire was fully answered by 171 (5%) neurologists. Sixty‐one percent of neurologists noticed an increase in patients with GBS during the ZIKV epidemic, and 30% experienced an increase in problems in managing GBS during this time. The most important limitations in the diagnosis and management of GBS included the availability of nerve conduction studies (NCS), beds in the Intensive Care Unit (ICU) and referral to rehabilitation centers. Most neurologists did not use a protocol for treating patients with GBS and the treatment practice varied. Increasing availability of NCS and beds in the ICU and rehabilitation centers, and the implementation of (inter)national guidelines, are critical in supporting Brazilian neurologist in their management of GBS, and are especially important in preparing for future outbreaks.

Transthyretin familial amyloidosis is the most common form of inherited systemic amyloidosis worldwide. The condition develops secondary to more than 100 different point mutations in the transthyretin gene (18q12.1). The mutations lead to abnormal amyloid deposits, mainly in the heart and peripheral nerves. Leptomeningeal and mainly ocular involvement is common. Although there are several different types of treatment available, ocular involvement, which occurs also in liver transplant recipients, remains a major challenge, progressing even in liver transplant recipients. Patients with ocular involvement require efficient ophthalmological follow-up to prevent vision loss. In this review, different forms of ocular involvement characterizing the subtypes of transthyretin mutations were described, and the effects of different treatments were summarized. Further research is necessary to fully elucidate these issues. RESUMO A amiloidose familiar por transtirretina é a forma mais comum de amiloidose sistêmica hereditária mundialmente. A condição é secundária a mais de 100 mutações ponto diferentes no gene da transtirretina (18q12.1). Mutações levam a depósitos anormais de amilóide principalmente no coração e nos nervos periféricos. O envolvimento leptomeníngeo, e principalmente ocular também é comum. Apesar do advento de várias formas diferentes de tratamento, o envolvimento ocular ainda é um grande problema, progredindo mesmo em pacientes submetidos à transplante hepático. Nesta revisão, avaliamos as diferentes formas de envolvimento ocular presentes entre os subtipos de mutações da transtirretina e os efeitos dos diferentes tratamentos disponíveis. O envolvimento ocular é desafiador na amiloidose familiar por transtirretina, exigindo acompanhamento oftalmológico eficiente para mitigar a perda de visão. Mais pesquisas são necessárias para auxiliar na resolução dessas questões.

In the history of Christianity, veneration of the Virgin Mary reached its greatest intensity in the XIII century. Her perceived impact on daily life was tremendous and not surprisingly this extended to the spheres of disease and healing. The purpose of this study is to compare the medical and neuropsychiatric findings in two XIII century Spanish texts of Marian miracles, both examples of the popular Catholicism (vs. official catholic doctrine). We analyzed the medical and neuropsychiatric events in the Cantigas de Santa Maria (Canticles of St. Mary, CSM), composed at the court of Alfonso X and the Milagros de Nuestra Señora (The Miracles of Our Lady, MNS), written by Gonzalo de Berceo. Among the 25 miracles reported in the MNS, medically relevant facts were addressed in 19 miracles with a total of 23 recorded events (including resurrection or escape from death in five) and demonic possession in three (one with witchcraft/deicide). The most common medical subjects were ergotism, obstetric-gynecological, sudden death, intellectual disability/illiteracy, encephalopathy/alcohol intoxication, suicide (with self-mutilation/castration), infanticide, infections, and absence of body decomposition after death. The 427 canticles in the CSM contain 270 medically relevant facts. Neuropsychiatric conditions were alluded to in 98 songs. Blindness and dystonia/weakness/deformities were the most common phenomena. Illuminations detailed many of the medical facts in the CSM, but not in the MNS. Medically relevant facts were described in both texts, but with more details in the CSM. Neurological conditions were more often described in the CSM, psychiatric conditions in the MNS.

Dificuldades no diagnóstico de Síndrome da Taquicardia Postural Ortostática (POTS) numa adolescente de 16 anos, com hipotireoidismo a 10 anos, apresenta sudorese, palidez, calor, taquicardia, fadiga e tontura. Após seis meses, houve recidiva pós-prandial, revertida com manobra de Trendelenburg. Tilt Test demonstrou em decúbito dorsal pressão arterial (PA) 106/71mmHg e frequência cardíaca (FC) 72bpm. Após terceiro minuto, PA 101/70mmHg e FC 99bpm. Além hipotireoidismo, não detectou-se outros fatores de risco para disautonomia. Propranolol (10mg, 12/12h) controlou sintomas. Diagnóstico de POTS é difícil em adolescentes, confundindo com Epilepsia e Síncope Neurocardiogênica. Nesse caso, hipotireoidismo parece ser fator causal da POTS.

Introduction: The septum pellucidum (SP) is formed by separated neural laminae, that subsequently merge. When there is no complete fusion of the laminae, there is persistence of the embryological Cavum, that can be named Cavum Septum pellucidum (CSP), Cavum Vergae or Cavum Septum pellucidum et Vergae (CSP et Vergae) according to its anterior-posterior length. Embryologically, CSP is related to the development of the corpus callosum and other cerebral structures. The SP belongs to the limbic system, and thus, it is possible that Cava persistence may lead to neuropsychiatry dysfunction. Objective: To review the literature about development and clinical significance of CSP. Methods: A review of literature of articles published on the database PUBMED. The following descriptors were used: “Cavum”, “Brain Cava” and “Cavum Septum Pellucidum”. The select articles had much information about development and clinical significance of CSP. Results and Discussion: Vestigial CSP are considered normal variants. However, several studies suggest that their persistence in adults may represent a form of midline cerebral dysgenesis. Studies attempted to link CSP to multiple neuropsychiatric disturbances, especially schizophrenia. There is relative agreement about the idea that large CSP are more likely to have pathological meanings, but their symptoms are not well recognized. Conclusion: There is evidence that persistent CSP, if large, may exhibit neuropsychic disorder, of unknown magnitude. Studies in the general population are scarce and with variable prevalence. Further comprehensive studies are necessary to better understand their clinical meaning. Introdução: O septo pelúcido (SP) é formado por duas lâminas neurais separadas, que se fundem após o nascimento. Quando não há fusão completa, tem-se a persistência do Cavum embriológico, que pode ser chamado Cavum Septum pellucidum (CSP), Cavum Vergae ou Cavum Septum pellucidum et Vergae (CSP et Vergae), dependendo da extensão anteroposterior. Embriologicamente, o CSP está relacionado à formação do corpo caloso e de outras estruturas cerebrais. O SP faz parte do sistema límbico, por isso há possibilidade de que Cava persistentes tenham repercussão nas funções neuropsíquicas. Objetivo: revisar a literatura sobre a formação e o significado clínico da persistência do CSP em adultos. Métodos: foi realizada revisão da literatura de artigos publicados na base de dados PUBMED, utilizando os descritores: “Cavum”, “Brain Cava” e “Cavum Septum Pellucidum”. Os artigos selecionados continham considerações sobre formação e possível significado clínico do CSP. Resultados e Discussão: CSP vestigiais são considerados como variantes da normalidade. Porém, vários estudos sugerem que a persistência de CSP com grandes dimensões pode representar uma disgenesia cerebral na linha média. Estudos tentam relacionar o CSP com múltiplos distúrbios neuropsiquiátricos, especialmente com esquizofrenia. De maneira geral, há relativo consenso de que os CSP alargados têm maior chance de representar significado patológico, embora suas manifestações não sejam bem reconhecidas. Conclusão: existem indícios de que CSP persistentes, quando alargados, podem manifestar-se como distúrbio neuropsíquico, de espectro ainda indefinido. Estudos em população geral ainda são escassos e com prevalências variadas. Trabalhos mais abrangentes são necessários para melhor entendimento de seu significado clínico.

Background The repetitive ElectroMagnetic Stimulation (rEMS) is an innocuous method applied to modulate neurocircuits in real-time to study the physiology of the central nervous system and treat neuropsychiatric conditions. Preliminary data suggest that spinal rEMS induces behavioral changes in awake rats. However, the mechanisms behind this phenomenon remain largely unknown. Methods Twenty-five male Wistar rats were divided into five subgroups of five animals each: one subgroup was drug-free, two subgroups received Levodopa + Benserazide 250 + 25 mg/kg for two or seven days, and the remaining two subgroups received Haloperidol 0.1 or 0.3 mg/kg for two days. The animals were restrained during sham rEMS (day 1) followed by real rEMS of the cervicothoracic region at a different day (day 2 or 7, depending on subgroup). Four behavioral parameters were quantified: Walking , Climbing , Grooming , and Cornering . Results rEMS reduced Walking and increased Cornering duration when applied over the cervicothoracic region of drug-free animals. A pretreatment with Levodopa + Benserazide for two or seven days induced an additional decrease in Walking after rEMS. This reduction was maximum after the treatment for seven days and associated with extinction of Climbing and increase in Cornering . A pretreatment with Haloperidol 0.1 mg/kg reduced Grooming after rEMS, but did not prevent the reduction in Walking . Conclusions Cervicothoracic rEMS induced complex immobility responses that are in part modulated by dopaminergic pathways in rats. Further studies are necessary to determine the specific mechanisms involved.

Dominant intermediate Charcot-Marie-Tooth neuropathy subtype C (DI-CMTC) was associated with mutations in the YARS gene, encoding tyrosyl-tRNA synthetase, in two large unrelated Bulgarian and US pedigrees and one sporadic case. Here for the first time we describe the clinical, neurophysiological and histopathological features, and phenotypic differences between these two DI-CMTC families. Twenty-one affected individuals from the US family and 27 from the Bulgarian family were evaluated. The mean age of onset in US subjects was 10.7 years in men and 7.3 years in women, while in the Bulgarian participants it was 18.2 years in men and 33.7 years in women. The course was slowly progressive. Extensor digitorum brevis atrophy was uniform. Atrophy and/or weakness of upper and lower limb muscles were found in over 50 % of the subjects. Nerve conduction studies (NCS) were abnormal in all US adults and five of six children and all Bulgarian patients except one asymptomatic 25-year-old man. Median motor NCS were in the range of 29.545.6 m/s in the US family and 24.757.8 m/s in the Bulgarian family. Sural sensory nerve action potentials were absent in 14/21 and 4/12 NCS from adult US and Bulgarian participants, respectively. Analysis of sural nerve biopsies from US patients revealed age-dependent morphological changes of axonal degeneration, absence of onion bulbs, and

Transthyretin familial amyloid polyneuropathy is an autosomal dominant inherited sensorimotor and autonomic polyneuropathy, which if untreated, leads to death in approximately 10 years. In Brazil, liver transplant and tafamidis are the only disease-modifying treatments available. This review consists of a consensus for the diagnosis, management and treatment for transthyretin familial amyloid polyneuropathy from the Peripheral Neuropathy Scientific Department of the Brazilian Academy of Neurology. The first and last authors produced a draft summarizing the main views on the subject and emailed the text to 10 other specialists. Relevant literature on this subject was reviewed by each participant and used for the individual review of the whole text. Each participant was expected to review the text and send a feedback review by e-mail. Thereafter, the 12 panelists got together at the city of Fortaleza, discussed the controversial points, and reached a consensus for the final text.

Objectives Investigate the acute effects of non-invasive ventilation (NIV) on cerebral blood flow (CBF) and on cognitive functions in COPD. Methods Nine non-hypercapnic stable COPD and twelve healthy controls were enrolled. CBF (transcranial Doppler), cognitive tests and cardiorespiratory response were performed at baseline, during one hour of NIV and after 30 min. Results Both groups had an increase in tidal volume and reduction in respiratory rate during NIV, but only controls showed PaCO2 reductions (41.2 ± 4.6 to 36.5 ± 7.3 in controls vs. 40.9 ± 4.5 to 42.9 ± 5.9 in COPD). During NIV CBF was significantly reduced in healthy controls and COPD, although this effect was less pronounced in the latter. At the same time, healthy controls demonstrated an improvement in cognitive executive function compared to COPD in the Trail Making Test part B (90.5 vs. 180s; respectively). Conclusion NIV application for one hour reversibly reduced CBF in healthy controls and non-hypercapnic stable COPD patients, despite no significant reductions of the PaCO2 in the latter group. It was associated with minor cognitive improvements in the executive function in healthy volunteers, but not in COPD.

Objective: To discuss the neuropsychiatric phenomena described in Cantigas de Santa Maria ( Canticles of St. Mary [ CSM ]). Background: CSM is a collection of 427 canticles composed in Galician-Portuguese between 1252 and 1284 at the Court of King Alfonso X the Wise of Spain (1221–1284). The canticles (of which 9 are repeated) include devotional and liturgical poems and 353 narrative stories consisting mainly of depictions of Marian miracles. Most are set to music and many are illustrated. Methods: We reviewed the canticles for description of miracles and other neuropsychiatric phenomena. Two neurologists reached a consensus about the descriptions. Results: Of the 353 miracles, 279 medically relevant facts (from 187 canticles) and 25 instances of resurrection were reported. Possible neuropsychiatric conditions were described in 98 canticles. Physicians were mentioned in 16 narratives. The most common neurologic conditions detailed were blindness (n = 17), dystonia, weakness, and deformities (n = 20). Other common conditions included psychosis (n = 15), speech disorder/deaf-mutism (n = 12), infections (n = 15), sexual dysfunction/infertility/obstetrical-gynecologic issues (n = 18), head trauma (n = 5), ergotism/St. Anthony9s fire (n = 7), and others. There were 9 instances of prodromic mystical experiences/hallucinations heralding death. Conclusions: While limited by retrospection and interpretation of neuropsychiatric phenomena in the medieval context, these short accounts are among the first descriptions of neuropsychiatric conditions in early Portuguese/Galician. They reflect how medieval societies used rational and irrational approaches to understand occurrences in their lives.

Co-morbid auto-immune disorders may affect 0.2% of the population. We present the clinical and electrodiagnostic findings of 2 patients with inflammatory bowel disease and myasthenia gravis from a Brazilian cohort of 218 inflammatory bowel disease patients. Patient 1: A 40 year-old man was diagnosed with ulcerative colitis at age 37 and underwent total colectomy 3 years later. After prednisone was tapered, he experienced a clinical relapse and was diagnosed with Crohn’s disease. He then developed quadriparesis, bilateral ptosis, dysphagia and dysarthria. Patient 2: A 41 year-old woman (diagnosed with ulcerative colitis and primary sclerosing cholangitis at age 35) developed speech impairment and ptosis. On both patients, symptoms quickly progressed over few weeks. Myasthenia gravis was diagnosed and confirmed by abnormal repetitive nerve stimulation and elevated anti-acetylcholine receptor antibody titers. Pyridostigmine and prednisone successfully treated both patients. Myasthenia gravis prevalence over 9 years was 0.9%. Myasthenia gravis clinical course was not significantly modified by inflammatory bowel disease relapses and should be suspected with new onset weakness.

Objective: Patients with Wilson’s disease (WD) may develop a wide variety of neuropsychiatric symptoms, but there are few reports of autonomic dysfunction. Here, we described evidence of small fiber and/or autonomic dysfunction in 4 patients with WD and levodopa-responsive parkinsonism. Method: We reviewed the charts of 4 patients with WD who underwent evaluation for the presence of neuromuscular dysfunction and water-induced skin wrinkling test (SWT). Results: Two men and 2 women (33±3.5 years) with WD were evaluated. They all had parkinsonism at some point during their disease course. Parkinsonism on patient 4 almost completely subsided with treatment of WD. Two patients had significant sensory and 2 significant autonomic complaints, including syncopal spells. NCS/EMG was normal in all but SWT was abnormal in half of them (mean 4-digit wrinkling of 0.25 and 1). Discussion: A subset of patients with WD exhibit evidence of abnormal skin wrinkling test (small fiber neuropathy).

Introduction. The Charcot-Marie-Tooth Disease (CMT) comprises a genetic heterogeneous group of motor and sensory inherited neuropathies, with autosomal dominant, recessive and X-linked forms. Objective. The aim of this study is to review the available medical literature about the main types of CMT4 (autosomal recessive demyelinating CMT forms). Method. We conducted an extensive literature review searching for articles written in English (or at least with abstracts in English), with description about the clinical characteristics, ethnic and geographic distribution of CMT4 using NCBI’s OMIM and pubmed database. Results. We identified and described the genes, clinical characteristics, ethnic and geographic distribution of 12 variants of CMT4: A, B1, B2, B3, C, D, E, F, G, H, J and “L” (SURF gene mutation, with undefined nomenclature and here named as “CMT4L”). Conclusion. We conclude that CMT4, due to its autosomal recessive inheritance, is more commonly localized in restricted ethnic and geographic regions, contrasting with other forms of CMT. Despite extreme varaibility, there is a tendency towards more severe phenotypes in CMT, and overlap with diseases such as Dejerine-Sottas syndrome (CMT3) and congenital hypomyelinating neuropathy (CHN).

Chikungunya virus is an alphavirus transmitted by the mosquito Aedes, mainly Aedes aegypti and Aedes albopictus, that can cause acute illness, mostly self-limited, characterized by fever, maculopapular rash, and disabling polyarthritis/arthralgia, with an incubation period of 1 to 12 days. Chikungunya was largely regarded as a non-fatal and self-limited disease, but recently, serious cases have been reported including some with severe involvement of the nervous system, such as meningoencephalitis, myelitis, polyradiculitis, and polyradiculoneuropathy. In this report, we describe the clinical and laboratory findings of two patients with encephalitis associated with chikungunya in a northeastern city in Brazil, who exhibited a good outcome, with improvement after treatment with i.v. immunoglobulin (IVIg).

Disorders of laughter and crying (DLC) are seen in several neuropsychiatric conditions. Their nomenclature remains under debate.We present the clinical and imaging findings of 17 patients with DLC and introduce a new classification based on phenomenology and pathogenesis. According to intensity and frequency of laughter and crying (observed behavioral output), patients were divided into hypoactive or hyperactive DLC and subdivided into 5 subtypes: sensory (positive and negative), motor (positive and negative), and mixed. The sensory subtype is represented by disorders of "feeling processing," whereas the motor subtype is represented by disorders of "emotion processing." "Positive" and "negative" describe elicitation by irritative vs destructive lesions, respectively.Among the patients studied, DLC resulted from ischemic stroke (n = 12), intracerebral hemorrhage (n = 2), gunshot wound (n = 1), amyotrophic lateral sclerosis (n = 1), or vestibular migraine (n = 1). Ten patients had lesions in the brainstem, 4 in the cerebral hemispheres, and 2 in sub-cortical-diencephalic structures. Six patients had negative motor DLC, 5 had positive sensory DLC, 4 had negative sensory DLC, and 2 had positive motor DLC. Phenomenology changed or progressed to mixed DLC in 7 patients.This novel phenomenological and pathomechanistic nomenclature explains all subtypes of DLC in neurologic, medical, and psychiatric conditions. Future studies are needed to validate it prospectively.

Spinal cord injury (SCI) is associated with severe autonomic dysfunction in both the acute and chronic phases. Upper gastrointestinal (GI) motor dysfunction has been previously reported in humans and rats. Gastric emptying (GE) of a solid meal--as measured by the [(13)C]-octanoic acid breath test--is delayed in the first 3 weeks after either spinal cord transection (SCT) or contusion (SCC) in rats. This is one of the main findings of a new paper by Qualls-Creekmore et al. in the current issue of this journal. Previous studies in rats only reported impairment of GE, intestinal and GI transit of liquid after SCI, but the authors observed that the delay of the GE of solid was more prominent after SCT than SCC. Recovery of the delay of GE of solid occurred at 6 weeks after SCC, but not after SCT. However, gastric motility changes persisted despite the functional normalization of the GE in rats with SCC. Bowel dysfunction is a major physical and psychological burden for SCI patients. Collaborative efforts, like the development of international standards to evaluate autonomic function after SCI will likely clarify the mechanisms of dysfunction and lead to the development of new therapeutic strategies.

The distinction of non-epileptic from epileptic events is difficult even for experienced neurologists. We retrospectively evaluated 59 dialeptic events from 27 patients admitted for video EEG monitoring to check whether heart rate (HR) analysis could help in differentiating dialeptic complex partial temporal lobe seizures (TLS) from dialeptic simple partial TLS, and non-epileptic dialeptic events. Baseline HR was increased in the simple partial TLS in comparison to complex partial TLS and non-epileptic groups (p

Background Several neurological diseases, especially different types of peripheral neuropathy (PN) are common in inflammatory bowel disease (IBD). Methods We prospectively evaluated the presence of PN in 121 patients with IBD (51 with Crohn's disease [CD] and 70 with ulcerative colitis [UC]) and 50 controls (gastritis and dyspepsia) over 3.5 years. Results A total of 15 patients (12.4%) with small-fiber neuropathy and IBD (7 CD and 8 UC) and 24 patients (19.8%) with large-fiber PN (12 CD and 12 UC) were diagnosed. Small-fiber neuropathy affected 6% and large-fiber PN affected 4% of the control patients. Patients with CD with PN were older, had more metabolic complications and more severe motor involvement than patients with UC with PN. Carpal tunnel syndrome was more common in patients with UC. Sural and median sensory nerves were the most commonly and severely affected sensory responses. Tibial, peroneal, median, and ulnar compound muscle action potential amplitudes were also significantly decreased in patients with CD and UC. In general, sensory and motor amplitudes were a more sensitive marker for PN in patients with IBD than conduction velocities. Conclusions In summary, PN is common in patients with IBD. It may be primarily related to IBD, phenotypically modified by metabolic complications. Its phenotype is diverse (most commonly small to predominantly axonal sensory large-fiber), but usually more severe in CD. It also includes ataxic and demyelinating forms. Results from our 10-year follow-up will elucidate the PN clinical course and the real impact of the comorbidities and new therapies.