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Congenital myasthenic syndromes (CMS) associated with pathogenic variants in the DOK7 gene (DOK7-CMS) have phenotypic overlap with other neuromuscular disorders associated with limb-girdle muscular weakness (LGMW). Genetic analysis of the most common mutation (c.1124_1127dupTGCC) in DOK7 was performed in 34 patients with "unexplained" LGMW associated with non-specific changes in muscle biopsy. Of the 34 patients, one patient showed the DOK7 c.1124_1127dupTGCC variant in homozygousity. Our study estimates the minimum prevalence of undiagnosed DOK7-CMS to be 2.9% in southern Brazilian patients from our centre. Our data confirm that clinicians should look for DOK7-CMS patients when the clinical manifestation is an 'unexplained' LGMW, mainly if associated with non-specific changes in muscle biopsy.

Left ventricular systolic dysfunction (LVSD) is a common finding in patients with Duchenne (DMD) and Becker (BMD) muscular dystrophies. Novel echocardiographic techniques have been used for the detection of LVSD in several heart diseases. We aim to compare cardiac anatomic and functional data studied by three-dimensional (3DE) and two-dimensional (2DE) echocardiography and to analyze the myocardial strain for the detection of early LVSD in DMD and BMD patients. We performed a cross-sectional study of 46 DMD and 14 BMD patients. We measured left atrium volume and left ventricle volumes and ejection fraction using 3DE and 2DE techniques. Myocardial strain analysis was derived from global longitudinal strain (GLS) measurements. GLS was measured by 2DE with the speckle tracking technique. The correlation between 3DE and 2DE for the measurement of left atrium volume as well as left ventricle diastolic and systolic volumes was strong. 2DE presented larger left atrium and left ventricle volumes. Left ventricle ejection fraction was similar between the two techniques. Myocardial strain analysis was able to detect early LVSD in 50.0% of DMD patients and in 9.1% of BMD patients. In conclusion, two-dimensional echocardiography appears to be a good alternative for the anatomical and functional evaluation of the left heart chambers in DMD and BMD patients. Myocardial strain analysis detects early LVSD in a sizable portion of patients with dystrophinopathies.

HIV-associated motor neuron disease (MND), or amyotrophic lateral sclerosis (ALS)-like syndrome associated with HIV infection, is a rare manifestation of HIV infection. HIV-associated MND has only been identified in few cases to date. We analysed two Brazilian patients with HIV infection who developed MND. The diagnosis of HIV infection was concomitant with diagnosis of MND in one patient and it occurred eight years before the MND symptoms in another patient. The manifestation of MND in our patients with HIV infection was similar to classic ALS. The antiretroviral therapy improves their HIV infection. However, slow progression of MND occurred in the two patients despite their antiretroviral therapy or HIV viral load (undetectable). We revised the international literature (PubMed database) of the patients reported with MND and HIV infection.

The relationship between myasthenia gravis (MG) and epilepsy has been rarely reported. As consequence, there are no specific guidelines for the management of these conditions when they mutually occur. We reported on three patients in whom epilepsy and MG are coexisting, but in different clinical settings. Two patients were treated with antiepileptic drugs which improved their symptoms. One patient has controlled the seizures after a successful anterior temporal lobectomy with no appreciable consequences to her MG. We discuss the difficulties in the management of epilepsy in patients with MG. In addition, we report on the first epileptic surgery in a MG patient, indicating that this surgical procedure as a safe option for the treatment of intractable epilepsy in patients with MG.

This study aimed to analyze the outcome and impact of pregnancy in women with myasthenia gravis (MG). Obstetric and clinical data were retrospectively analyzed before, during and after pregnancy. Predictors of outcome were studied. We included 35 pregnancies from 21 MG patients. In the course of MG symptoms in 30 pregnancies with live births, 50% deteriorated (mainly during the second trimester, p = 0.028), 30% improved, and 20% remained unchanged. The deterioration group had more frequent abnormal repetitive nerve stimulation (RNS) (p = 0.028) and lower myasthenia gravis composite (MGC) scores (p = 0.045) before pregnancy. The improvement group was associated with higher MGC scores (p = 0.012) before pregnancy. The no-change group was associated with longer duration of MG (p = 0.026) and normal RNS (p = 0.008) before pregnancy. The course of MG in the second pregnancy was different from that in the previous pregnancy in 65.3% of cases. Obstetric complications were reported in 20 pregnancies; the most common was preterm premature rupture of membranes (PPROM) (25.8%), and the most severe were abortion (11.4%) and fetal death (2.9%). Most of the patients delivered via caesarean section (66.7%). Spinal anesthesia was performed in 73.3%. Transient neonatal myasthenia gravis occurred in 12.9% of live-born infants, and no predictors were found. In conclusion, severity and duration of MG, RNS and treatment influence MG and pregnancy. Pregnant MG patients have greater rates of PPROM and caesarean delivery. Our data suggest that duration of MG, MGC and RNS before pregnancy may be useful in helping to predict the course of MG during pregnancy.

Background Because MS-related fatigue could be associated with enhanced proinflammatory cytokine production, drugs with immunomodulatories properties, such as salbutamol, may represent an alternative treatment. We aimed to evaluate the effect of salbutamol on MS-related fatigue. Methods Thirty patients with relapsing-remitting MS who were between 18 and 69 years old, and suffering from fatigue, were evaluated with the Fatigue Severity Scale (FSS) and the Brazilian version of the neurological fatigue index for multiple sclerosis (NFI/MS-BR). They received salbutamol 2 mg twice a day or a placebo in a pilot randomized, double-masked placebo-controlled trial. The primary outcome was the change in the FSS score at the end of 90 days. The secondary outcome was the efficacy, represented by changes in their scores on the NFI/MS-BR subdomains (in the same period) and the Expanded Disability Status Scale (EDSS) at the end of 90 days. Results Thirty subjects were allocated to receive either salbutamol (14) or a placebo (16). There was no superiority of salbutamol over the placebo in the FSS outcome at 30 (p ==0.498), 60 (p = 0.854) and 90 (p = 0.240) days. There was no a significant decrease in the proportion of patients with severe or moderate fatigue in the salbutamol group at the end of the follow-up. The scores on the NFI/MS-BR and its subscales did not improve significantly with treatment. No significant difference was observed in the EDSS outcome (p = 0.313). No serious adverse events were found. An increase in heart rate was evident in the salbutamol group only in the first 30 days, but without statistical significance in relation to placebo (p = 0.077). Conclusion : Treatment with salbutamol does not improve fatigue in patients with relapsing-remitting MS.

The most common idiopathic inflammatory myopathies in children include juvenile dermatomyositis, juvenile polymyositis, and myositis associated with another autoimmune disease (overlap myositis). Idiopathic inflammatory myopathies manifest different characteristics affecting children. Only a few investigations of childhood idiopathic inflammatory myopathies were reported, involving 27 patients. In addition, clinical findings, serum muscular enzyme levels, results of electromyography studies, muscle biopsy features, and treatment responses were studied. Seventeen female and 10 male were classified as exhibiting juvenile dermatomyositis (n = 19), juvenile polymyositis (n = 6), or overlap myositis (n = 2). Overlap myositis was associated with systemic sclerosis and systemic erythematous lupus. The mean age at onset was 6.1 years for juvenile dermatomyositis, 4.9 years for juvenile polymyositis, and 8.5 years for overlap myositis. The most common signs included proximal weakness and myalgia. The serum creatine kinase level was increased in 48.2% of patients. An electromyography study revealed myopathic features in 85% of patients. Muscle biopsies led to observations of inflammatory infiltrates with preferential perivascular involvement in the juvenile dermatomyositis group, and endomysial involvement in the juvenile polymyositis group. Fiber atrophy was predominantly perifascicular in the juvenile dermatomyositis group. Treatment with prednisone improved the findings in 81.5% of children.

BACKGROUND: Long-term data on the clinical follow-up and the treatment effectiveness of Wilson's disease are limited because of the low disease frequency. This study evaluated a retrospective cohort of Wilson's disease patients from southern Brazil during a 40-year follow-up period. METHODS: Thirty-six Wilson's disease patients, diagnosed from 1971 to 2010, were retrospectively evaluated according to their clinical presentation, epidemiological and social features, response to therapy and outcome. RESULTS: Examining the patients' continental origins showed that 74.5% had a European ancestor. The mean age at the initial symptom presentation was 23.3 ± 9.3 years, with a delay of 27.5 ± 41.9 months until definitive diagnosis. At presentation, hepatic symptoms were predominant (38.9%), followed by mixed symptoms (hepatic and neuropsychiatric) (30.6%) and neuropsychiatric symptoms (25%). Kayser-Fleischer rings were identified in 55.6% of patients, with a higher frequency among those patients with neuropsychiatric symptoms (77.8%). Eighteen patients developed neuropsychiatric features, most commonly cerebellar syndrome. Neuroradiological imaging abnormalities were observed in 72.2% of these patients. Chronic liver disease was detected in 68% of the patients with hepatic symptoms. 94.2% of all the patients were treated with D-penicillamine for a mean time of 129.9 ± 108.3 months. Other treatments included zinc salts, combined therapy and liver transplantation. After initiating therapy, 78.8% of the patients had a stable or improved outcome, and the overall survival rate was 90.1%. CONCLUSION: This study is the first retrospective description of a population of Wilson's disease patients of mainly European continental origin who live in southern Brazil. Wilson's disease is treatable if correctly diagnosed, and an adequate quality of life can be achieved, resulting in a long overall survival.

Objective To investigate the etiologic diagnoses of parkinsonism, underlining aspects of each form and comparing our findings with those published in a similar setting, 10 years before. Methods A large cohort of 1528 patients with parkinsonism was analyzed, gathering data on demography, motor and non-motor characteristics, as well as the final etiologic diagnoses based on established criteria. Results Parkinson's disease (PD) was the most common diagnosis representing 74.7%, followed by drug-induced parkinsonism (DIP) in 7.9%, vascular parkinsonism (VP) in 3.9%, other neurodegenerative disorders in 10%, and rare sporadic causes, divided as genetic, infectious and others, that summed 3.5%. Comparative analysis of these groups showed that each has particularities that extend beyond their diagnostic criteria. Conclusions The main conclusions are that the most important causes of parkinsonism in this setting are typical, with PD been the most common diagnosis, although other causes were frequent, encompassing one fourth of all cases. Although DIP was identified in a particularly large part of this cohort, this proportion is smaller than demonstrated previously in a Brazilian study conducted in the 90s. This decrease probably reflects higher awareness regarding the risk of this motor complication and the more widely used newer antipsychotics.

Background and purpose Patent foramen ovale (PFO) can be diagnosed by contrast-enhanced transcranial Doppler (cTCD), but no definitive criteria exist to correlate the results obtained from cTCD with diagnoses of PFO obtained by contrast-enhanced transesophageal echocardiography (cTEE). The aim of the present study was to analyze markers in the positive RLS by cTCD that confirm the PFO by cTEE. Methods Twenty-six stroke patients who had previously submitted to cTEE, 16 with PFO (PFO group) and 10 without PFO (no-PFO group), were evaluated for three markers based on a positive cTCD test. The number of microembolic signs (MES), the latency time (LT) to the first MES and the duration time (DT) of MES were evaluated to look for a difference between the PFO and no-PFO group. Results The PFO group had higher MES (80.9±124.5 vs. 10.2±25.6, p p =0.02) and longer DT (21.4±17.4 vs. 11.7±12.5, p =0.013) compared with the no-PFO group. Considering only MCA tests with more than 9 MES and LT shorter than 9s, 30% of patients from the PFO group had positive tests compared with no patients from the no-PFO group. This cutoff demonstrates a specificity and positive predictive value of 100%. Conclusions The rule of nine (>9 MES and LT

Paracoccidioidomycosis (PCM) is a chronic granulomatous infectious disease, whose etiologic agent is the fungus Paracoccidioides brasiliensis. The central nervous system (CNS) involvement with paracoccidioidomycosis (NPCM) occurs more frequently than has been admitted in the past. There are some major histocompatibility complex antigen association studies with systemic paracoccidioidomycosis. Some indicate a positive association with HLA antigens, but there is no study with the involvement of the CNS. To investigate why not all cases of systemic PCM show the involvement of the CNS and whether genetic factors are involved, we studied 6 patients with NPCM, from the neuroinfection outpatient clinic. The patients were typed for class I and class II antigens by a microlymphocytoxity standard test. The HLA antigen frequencies found in this study in patients with NPCM were not different from the alleles frequencies observed in the Paraná population.

Introduction Salbutamol is a selective B2-adrenergic agonist, which has previously been described to be associated with partial improvement of myasthenia gravis and congenital myasthenic syndromes (CMS). In this study, we analyzed the effect of salbutamol in five patients with Dok-7 CMS. Methods We studied 5 patients (2 male and 3 female), with a mean age of 27 ± 11.06 years, who harbored c.1124_1127dupTGCC, p.G64R and/or p.S45L mutations in DOK7 gene. Salbutamol was given at a dose of 2 mg three times daily (6 mg/day) to all patients. The response was assessed by QMG score at baseline, 3, 6, 9 and 12 months; ADL-MG score and 6 minute walk test at baseline and after 12 months during follow-up clinic visits. Side effect profile of salbutamol was also evaluated. Results We noted an increasingly positive response as measured by the QMG score after 3 months of salbutamol treatment. Improvement in specific subcomponents of the QMG score such as leg outstretched in 45° supine was most marked. In ADL-MG scores and 6 minute walk test, comparison between baseline and after 12 months revealed a clear beneficial response. Salbutamol was well tolerated in all patients. Conclusions Salbutamol is an effective treatment in Dok-7 CMS. This study provides class IV evidence that salbutamol given at a dose 6 mg/day improves function as measured by the QMG score, ADL-MG score and 6 minute walk test.

Stiff person syndrome (SPS) is a rare immune-mediated disorder of the central nervous system characterized by muscle rigidity and episodic muscle spasms. The diagnosis of SPS is based on electrophysiological studies. We analyzed the electrophysiological features in four patients from Brazil who fulfilled the clinical criteria for SPS. The most common electrophysiological abnormalities were continuous motor unit activity, co-contracting, and the presence of the cutaneomuscular reflex. Despite all patients having clinical characteristics of SPS during the disease, no patient met all the electrophysiological criteria for SPS even after repeat electrophysiological studies. This shows that a diagnosis of SPS should not be restricted to patients with all the classic electrophysiological changes but should be considered in the presence of one or some of those changes.

Acute organophosphate (OP) poisoning is commonly seen in emergency medicine. Neurologists must be alert to detect neuromuscular transmission failure and other neurological complications that follow OP poisoning. We report a 37-year-old male with acute OP poisoning to emphasize the electrophysiological abnormalities during the intermediate syndrome (IMS). Motor nerve conduction studies revealed that a single nerve stimulation evoked a repetitive compound muscle action potential, whereas repetitive nerve stimulation resulted in a combination of a decrement-increment pattern and a repetitive fade response. Thus, electrophysiological studies can be used to monitor patients with IMS, and these test results correlate well with clinical findings in acute OP poisoning.

Objective Spinocerebellar ataxia type 8 (SCA 8) is an autosomal dominant disorder characterized by cerebellar ataxia with additional features, such as upper motor neuron signs, urinary incontinence and dysphagia. From a clinical standpoint, SCA 8 and the cerebellar form of multiple system atrophy (MSA-C) share several common features. Methods We studied the presence of expanded SCA 8 alleles in 10 sporadic patients with probable MSA-C. Results We found 1 patient with a heterozygous CTA/CTG repeat expansion in the pathological range. Clinically this subject presented no features that differed from the other subjects carrying smaller repeat sizes. Conclusions We believe that the association of SCA 8 repeat expansions with sporadic, atypical and heterogeneous phenotypes is debatable and should be interpreted with caution. Our personal conclusion is that testing in such patients may become a source of diagnostic confusion.

Here we report on a 44-year old woman presenting with both myasthenia gravis (MG) and neuromyelitis optica (NMO). MRI showed transverse myelitis extending from C2 to T4, multifocal demyelinating lesions in the supratentorial white matter, and left optic neuritis. Serological analysis demonstrated antibodies to acetylcholine receptors as well as NMO-IgG. To our knowledge, this is the first case of NMO-IgG positive NMO in a patient with MG but no history of thymectomy or immunosuppression.

Background: Although no causal linkage between hypothyroidism and Parkinson's disease (PD) has been demonstrated so far, both share common manifestations and coexistence can be a source of diagnostic delay and confusion. Purpose: To assess thyroid function in patients with PD. Scope. Ninety-five PD patients and 102 age-matched controls were assessed for hypothyroidism through clinical evaluation and laboratory screening. Results: In the PD group 13.7% were hypothyroid versus 10.8% in the control group. Statistical analysis did not show a significant difference (p=0.3681). Conclusion. Although hypothyroidism was not more prevalent in our PD patients in comparison with the control group, we believe that given the potential overlap of symptoms and signs, thyroid function should be assessed in patients showing worsening of symptoms that cannot be explained by disease progression or resistance to therapy adjustment; screening should take into account the particular acute effect of levodopa on serum TSH levels.

Spinocerebellar ataxia type 10 is an autosomal dominant neurodegenerative disorder. It was initially described in Mexican families presenting with ataxia and epilepsy, with or without polyneuropathy, pyramidal signs and cognitive symptoms. The authors report three patients from the same family who were asymptomatic until gestation and puerperium, when they developed symptoms and signs suggestive of the syndrome. Genetic diagnosis was made in the three patients. The authors hypothesize that hormonal changes are likely to influence the manifestation of the condition.