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Background Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects the upper and lower motor neurons. The correct diagnosis at the onset of the disease is sometimes very difficult, due to the symptoms being very similar to those of other neurological syndromes. Objective This study aimed to analyze the initial manifestations, the specialty of the first physician visited due the initial complaint, the misdiagnoses, as well as the unnecessary surgical interventions in a new ALS Brazilian population. Methods The medical records of 173 patients with typical ALS were reviewed. Results The present study demonstrated that other symptoms, besides weakness, were very frequent as initial presentation of ALS, and orthopedics was the medical specialty most sought by patients at the onset of symptoms. Our frequency of misdiagnoses was 69.7%, and in 7.1% of them, an unnecessary surgical intervention was performed. Conclusions Amyotrophic lateral sclerosis presents a very large pool of signs and symptoms; therefore, there is an urgent need of increasing the disease awareness to other specialties due to the high frequency of misdiagnoses observed in clinical practice. Resumo Antecedentes A esclerose lateral amiotrófica (ELA) é uma doença neurodegenerativa que afeta os neurônios motores superior e inferior. O diagnóstico correto no início da doença é, às vezes, muito difícil, pois os sintomas de início são muito semelhantes aos de outras síndromes neurológicas. Objetivo Este estudo teve como objetivo analisar as manifestações iniciais, a especialidade do primeiro médico visitado devido à queixa inicial, os diagnósticos errôneos, bem como as intervenções cirúrgicas desnecessárias em uma nova população brasileira acometida por ELA. Métodos Os prontuários médicos de 173 pacientes com ELA típica foram revisados. Resultados O presente estudo demonstrou que outros sintomas, além da fraqueza, foram muito frequentes como apresentação inicial da ELA, sendo a ortopedia a especialidade médica mais procurada pelos pacientes no início dos sintomas. Nossa frequência de diagnósticos errôneos foi de 69,7%, e em 7,1% deles foi realizada intervenção cirúrgica desnecessária. Conclusões A ELA apresenta um conjunto amplo de sinais e sintomas; portanto, há necessidade urgente de uma melhor educação de outras especialidades devido à alta frequência de diagnósticos equivocados observada na prática clínica.

© 2020 Elsevier Ltd. All rights reserved., Background: Hereditary transthyretin-mediated amyloidosis is a rare, inherited, progressive disease caused by mutations in the transthyretin (TTR) gene. We assessed the safety and efficacy of long-term treatment with patisiran, an RNA interference therapeutic that inhibits TTR production, in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy. Methods: This multicentre, open-label extension (OLE) trial enrolled patients at 43 hospitals or clinical centres in 19 countries as of Sept 24, 2018. Patients were eligible if they had completed the phase 3 APOLLO or phase 2 OLE parent studies and tolerated the study drug. Eligible patients from APOLLO (patisiran and placebo groups) and the phase 2 OLE (patisiran group) studies enrolled in this global OLE trial and received patisiran 0·3 mg/kg by intravenous infusion every 3 weeks with plans to continue to do so for up to 5 years. Efficacy assessments included measures of polyneuropathy (modified Neuropathy Impairment Score +7 [mNIS+7]), quality of life, autonomic symptoms, nutritional status, disability, ambulation status, motor function, and cardiac stress, with analysis by study groups (APOLLO-placebo, APOLLO-patisiran, phase 2 OLE patisiran) based on allocation in the parent trial. The global OLE is ongoing with no new enrolment, and current findings are based on the interim analysis of the patients who had completed 12-month efficacy assessments as of the data cutoff. Safety analyses included all patients who received one or more dose of patisiran up to the data cutoff. This study is registered with ClinicalTrials.gov, NCT02510261. Findings: Between July 13, 2015, and Aug 21, 2017, of 212 eligible patients, 211 were enrolled: 137 patients from the APOLLO-patisiran group, 49 from the APOLLO-placebo group, and 25 from the phase 2 OLE patisiran group. At the data cutoff on Sept 24, 2018, 126 (92%) of 137 patients from the APOLLO-patisiran group, 38 (78%) of 49 from the APOLLO-placebo group, and 25 (100%) of 25 from the phase 2 OLE patisiran group had completed 12-month assessments. At 12 months, improvements in mNIS+7 with patisiran were sustained from parent study baseline with treatment in the global OLE (APOLLO-patisiran mean change -4·0, 95 % CI -7·7 to -0·3; phase 2 OLE patisiran -4·7, -11·9 to 2·4). Mean mNIS+7 score improved from global OLE enrolment in the APOLLO-placebo group (mean change from global OLE enrolment -1·4, 95% CI -6·2 to 3·5). Overall, 204 (97%) of 211 patients reported adverse events, 82 (39%) reported serious adverse events, and there were 23 (11%) deaths. Serious adverse events were more frequent in the APOLLO-placebo group (28 [57%] of 49) than in the APOLLO-patisiran (48 [35%] of 137) or phase 2 OLE patisiran (six [24%] of 25) groups. The most common treatment-related adverse event was mild or moderate infusion-related reactions. The frequency of deaths in the global OLE was higher in the APOLLO-placebo group (13 [27%] of 49), who had a higher disease burden than the APOLLO-patisiran (ten [7%] of 137) and phase 2 OLE patisiran (0 of 25) groups. Interpretation: In this interim 12-month analysis of the ongoing global OLE study, patisiran appeared to maintain efficacy with an acceptable safety profile in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy. Continued long-term follow-up will be important for the overall assessment of safety and efficacy with patisiran.

Myelin oligodendrocyte glycoprotein-immunoglobulin G (IgG)-associated optic neuritis has been established as a new entity of immune-mediated optic neuropathy. Patients usually present with recurrent optic neuritis, often bilaterally with initially severe vision loss and optic disc edema. However, in contrast to aquaporin 4-IgG-seropositive neuromyelitis optica spectrum disorder, visual recovery tends to be more favorable, with good response to steroid treatment. Another important differential diagnosis of myelin oligodendrocyte glycoprotein-IgG--associated optic neuritis is multiple sclerosis. Close monitoring for signs of relapse and long-term immunosuppression may be considered to maintain optimal visual function. The diagnosis can be made on the basis of the presence of a specific, usually serological, antibody against myelin oligodendrocyte glycoprotein (IgG; cell-based assay), and a demyelinating event (optic neuritis, myelitis, brainstem syndrome, or cortical lesions with seizures). The clinical spectrum of this newly recognized inflammatory demyelinating disease is expanding rapidly. We briefly review the epidemiological characteristics, clinical manifestations, diagnostic considerations, and treatment options of myelin oligodendrocyte glycoprotein-IgG-associated optic neuritis. RESUMO A neurite óptica associada à glicoproteína de oligodendrócito de mielina-IgG foi estabelecida como uma nova entidade de neuropatia óptica imunomediada. Tipicamente os pacientes apresentam neurite óptica recorrente, muitas vezes bilateral, com perda de visão frequentemente severa e alta prevalência de edema do disco óptico na fase aguda. No entanto, em contraste com neuromyelitis optica spectrum disorder associada com presença de anticorpo contra aquaporina 4, a recuperação visual tende a ser mais favorável e responde bem ao tratamento com corticoide em altas doses. A esclerose múltipla representa outro importante diagnóstico diferencial de glicoproteína de oligodendrócito de mielina-IgG. O diagnóstico pode ser feito com base na presença de um anticorpo específico, geralmente sorológico contra glicoproteína de oligodendrócito de mielina (IgG, ensaio baseado em células), e presença de evento desmielinizante (neurite óptica, mielite, síndrome do tronco cerebral, lesões corticais com convulsões). O espectro clínico desta doença desmielinizante inflamatória recém-reconhecida está se expandindo rapidamente. Faremos uma breve revisão das características epidemiológicas, manifestações clínicas, considerações diagnósticas e opções de tratamento da neurite óptica associada à glicoproteína de oligodendrócito de mielina-IgG.

Background: The “1/3″ brain magnetic resonance imaging (MRI) criteria including 1) a lesion adjacent to the lateral ventricle and in the inferior temporal lobe, or 2) a juxtacortical lesion, or 3) a Dawson finger-type lesion were shown to distinguish multiple sclerosis (MS) from antibody-mediated conditions. In this large multicentre study, we aimed to assess how the criteria perform 1) in different onset phenotypes, 2) distinct ethnic groups, 3) when the absence of myelin oligodendrocyte glycoprotein antibody (MOG-Ab)-associated disease (MOGAD)-typical fluffy infratentorial (FIT) lesions and longitudinally extensive transverse myelitis (LETM) lesions are added as features (“2/4″ and 3/5″ criteria, respectively). Methods: 577 patients with MS (n = 332), aquaporin-4 antibody (AQP4-Ab) neuromyelitis optica spectrum disorder (NMOSD) (n = 196) and MOGAD (n = 49) were recruited from 6 international centres (Buenos Aires, Sao Paolo, Maracaibo, Goyang, Oxford and Milan). Imaging scans were obtained at disease onset or relapse. Results: Adding the absence of FIT lesions increased the specificity of the “1/3″ criteria vs. AQP4-Ab NMOSD from 84.7% to 87.2% and vs. MOGAD from 85.7% to 93.9% without compromising their sensitivity (86%). In particular, for those presenting with brain/brainstem attacks “2/4″ had significantly higher specificity than “1/3″ (85% vs. 80% against AQP4-Ab NMOSD, 88.9% vs. 72.2% against MOGAD). Positive predictive values of the “1/3″ criteria for MS were lowest for Asian patients (84.8 vs. 99.1% for White) but were significantly increased by adding further criteria (94.1% for “3/5″). Conclusion: The “1/3″ criteria perform well in discriminating MS from NMOSD and MOGAD regardless of ethnic background and clinical scenario. Adding the absence of FIT lesions increases the specificity in those presenting with brain/brainstem symptoms.

Disability in leprosy is a direct consequence of damage to the peripheral nervous system which is usually worse in patients with no skin manifestations, an underdiagnosed subtype of leprosy known as primary neural leprosy. We evaluated clinical, neurophysiological and laboratory findings of 164 patients with definite and probable primary neural leprosy diagnoses. To better understand the disease progression and to improve primary neural leprosy clinical recognition we compared the characteristics of patients with short (≤12 months) and long (>12 months) disease duration. Positive and negative symptoms mediated by small-fibres were frequent at presentation (∼95%), and symptoms tend to manifest first in the upper limbs (∼68%). There is a consistent phenotypic variability between the aforementioned groups. Deep sensory modalities were spared in patients evaluated within the first 12 months of the disease, and were only affected in patients with longer disease duration (∼12%). Deep tendon reflexes abnormalities were most frequent in patients with longer disease duration (P < 0.001), as well as motor deficits (P = 0.002). Damage to large fibres (sensory and motor) is a latter event in primary neural leprosy. Grade-2 disability and nerve thickening was also more frequent in cases with long disease duration (P < 0.001). Primary neural leprosy progresses over time and there is a marked difference in clinical phenotype between patients with short and long disease duration. Patients assessed within the first 12 months of symptom onset had a non-length-dependent predominant small-fibre sensory neuropathy, whilst patients with chronic disease presented an asymmetrical all diameter sensory-motor neuropathy and patchily decreased/absent deep tendon reflexes.

Multiple sclerosis (MS) management presently aims to reach a state of no (or minimal) evidence of disease activity. The development and commercialization of new drugs has led to a renewed interest in family planning, since patients with MS may face a future with reduced (or no) disease-related neurological disability. The advice of neurologists is often sought by patients who want to have children and need to know more about disease control at conception and during pregnancy and the puerperium. When MS is well controlled, the simple withdrawal of drugs for patients who intend to conceive is not an option. On the other hand, not all treatments presently recommended for MS are considered safe during conception, pregnancy and/or breastfeeding. The objective of the present study was to summarize the practical and evidence-based recommendations for family planning when our patients (women and men) have MS. Funding TEVA Pharmaceutical Brazil.

In answer to the call for improved accessibility of neuropsychological services to the international community, the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS; MS) was validated in multiple, non-English-speaking countries. It was created to monitor processing speed and learning in MS patients, including abbreviated versions of the Symbol Digit Modalities Test, California Verbal Learning Test, 2nd Edition, and the Brief Visuospatial Memory Test, Revised. The objective of the present study was to examine whether participant nationality impacts performance above and beyond common demographic correlates.We combined published data-sets from Argentina, Brazil, Czech Republic, Iran, and the U.S.A. resulting in a database of 1,097 healthy adults, before examining the data via multiple regression.Nationality significantly predicted performance on all three BICAMS tests after controlling for age and years of education. Interactions among the core predictor variables were non-significant.We demonstrated that nationality significantly influences BICAMS performance and established the importance of the inclusion of a nationality variable when international norms for the BICAMS are constructed.

We aimed to assess the clinical, paraclinical, imaging and prognostic features of patients with late-onset neuromyelitis optica spectrum disorder (LO-NMOSD; ≥ 50 years at disease onset) LO-NMOSD, compared with early onset-NMOSD (EO-NMOSD, ≤ 49 years at disease onset), in Latin American (LATAM). We retrospectively reviewed the medical records of patients with NMOSD, as defined using the 2015 validated diagnostic criteria. We included patients from Argentina, Brazil and Venezuela. They were divided into: LO-NMOSD and EO-NMOSD and comparison among the groups were performed. Among these 140 NMOSD patients, 24 (17.1%) were LO-NMOSD; 64% were positive for aquaporin-4 antibodies; and 41.5% of this population cohort was non-Caucasian. Severe disability [expanded disability status scale (EDSS) ≥ 6] at the last follow-up and presence of comorbidities were significantly associated with LO-NMOSD, compared with EO-NMOSD. LO-NMOSD patients had a shorter median time to EDSS ≥ 4 than EO-NMOSD patients (46 vs. 60 months; log-rank test p = 0.0006). Furthermore, we observed a positive correlation between age at onset and EDSS score at the last follow-up (Spearman r = 0.34, p

Made available in DSpace on 2018-11-26T22:40:49Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-08-01. Added 1 bitstream(s) on 2019-10-09T18:27:56Z : No. of bitstreams: 1 S0004-282X2018000800539.pdf: 336862 bytes, checksum: 861f2018734ed5dc938f69878cf50b6e (MD5) Biogen Idec Genzyme Merck Novartis Rocha Teva Roche Sanofi-Genzyme World Federation of Neurology European Committee on Treatment and Research in Multiple Sclerosis Biogen Schering Biogen Indec Merck-Serono Teva (EMOCEMP Study-NCT) Euroimmun AG Shire Quest/Athena Diagnostics Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Bayer Partners MS Center, Harvard Medical School Distrito Federal Research Foundation (FAP-DF) Libbs Sanofi Serono Teva Pharmaceuticals Sonofi-Genzyme Novartis-PPD Merck Serono Bayer Health Care Ipsen Sanofi Genzyme The expanding therapeutic arsenal in multiple sclerosis (MS) has allowed for more effective and personalized treatment, but the choice and management of disease-modifying therapies (DMTs) is becoming increasingly complex. In this context, experts from the Brazilian Committee on Treatment and Research in Multiple Sclerosis and the Neuroimmunology Scientific Department of the Brazilian Academy of Neurology have convened to establish this Brazilian Consensus for the Treatment of MS, based on their understanding that neurologists should be able to prescribe MS DMTs according to what is better for each patient, based on up-to-date evidence and practice. We herein propose practical recommendations for the treatment of MS, with the main focus on the choice and management of DMTs, as well as present a review of the scientific rationale supporting therapeutic strategies in MS. Univ Sao Paulo, Fac Med Ribeirao Preto, Hosp Clin Ribeirao Preto, Ribeirao Preto, SP, Brazil Pontificia Univ Catolica Rio Grande do Sul, Porto Alegre, RS, Brazil Univ Sao Paulo, Fac Med, Hosp Clin, Sao Paulo, SP, Brazil Univ Fed Minas Gerais, Ctr Invest Esclerose Multipla Minas Gerais, Belo Horizonte, MG, Brazil Univ Jose Rosario Vellano, Belo Horizonte, MG, Brazil Univ Fed Estado Rio de Janeiro, Rio De Janeiro, RJ, Brazil Hosp Restauracao, Recife, PE, Brazil Clin Goncalves Dias, Curitiba, Parana, Brazil Univ Estadual Campinas, Campinas, SP, Brazil Clin Privada, Cuiaba, MT, Brazil Hosp Sao Rafael, Salvador, BA, Brazil Univ Fed Fluminense, Niteroi, RJ, Brazil Fundacac Ctr Integrado Apoio Portador Deficiencia, Joao Pessoa, Paraiba, Brazil Univ Brasilia, Brasilia, DF, Brazil Univ Catolica Brasilia, Brasilia, DF, Brazil Santa Casa Misericordia Londrina, Londrina, PR, Brazil Univ Fed Goias, Fac Med, Goiania, Go, Brazil Clin Neurol & Endocrinol, Brasilia, DF, Brazil Univ Estadual Paulista, Sao Paulo, SP, Brazil Inst Neurol Curitiba, Curitiba, Parana, Brazil Univ Regiao Joinville, Joinville, SC, Brazil Univ Fed Amazonas, Hosp Univ Getulio Vargas, Manaus, Amazonas, Brazil Pontificia Univ Catolica Sao Paulo, Sorocaba, SP, Brazil Senne Liquor Diagnost, Sao Paulo, SP, Brazil Hosp Cruz Azul, Sao Paulo, SP, Brazil Fac Sao Leopoldo Mandic, Campinas, SP, Brazil Hosp Israelita Albert Einstein, Sao Paulo, SP, Brazil Univ Fed Uberlandia, Uberlandia, MG, Brazil Hosp Base Dist Fed, Brasilia, DF, Brazil Imperial Hosp Caridade, Florianopolis, SC, Brazil Escola Bahiana Med & Saude Publ, Salvador, BA, Brazil Univ Estadual Paulista, Sao Paulo, SP, Brazil Teva (EMOCEMP Study-NCT): 61080516.4.1001.5336

To investigate the reliability and validity of a Brazilian-Portuguese adaptation of the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS).A Brazilian sample of 58 multiple sclerosis (MS) patients and 58 healthy controls (HC) were administered the Brazilian-Portuguese BICAMS test battery, comprising the Symbol Digit Modalities Test (SDMT), California Verbal Learning Test Second Edition (CVLT2), and the Brief Visuospatial Memory Test Revised (BVMTR). Mean differences between groups on BICAMS tests were assessed using analysis of covariance (ANCOVA), controlling for age, gender, education, anxiety, and depression. Test-retest data were obtained from 49 of the MS patients, two weeks after the initial assessment.The MS patient group scored significantly lower on all BICAMS tests (CVLT2 F1,110 = 28.99, p .001; BVMTR F1,110 = 7.77, p .01; SDMT F1,110 = 21.09, p .001). Mixed-factor ANCOVAs tested differences in learning curves across trials for CVLT2 and BVMTR. HCs had significantly steeper learning curves on both CVLT2 (F1,111 = 10.82, p .01) and BVMTR (F1,110 = 7.816, p .01). These findings support diagnostic validity of the Brazilian-Portuguese adaptation. Test-retest reliability was satisfactory for SDMT, CVLT2, and BVMTR (.86, .84, and .77, respectively).The results suggest that this Brazilian version of the BICAMS will be a valid and reliable measure once complete normative data become available.

Multiple Sclerosis (MS) is an inflammatory neurodegenerative disease that affects approximately 2.5 million people globally. Even though the etiology of MS remains unknown, it is accepted that it involves a combination of genetic alterations and environmental factors. Here, after performing whole exome sequencing, we found a MS patient harboring a rare and homozygous single nucleotide variant (SNV; rs61745847) of the G-protein coupled receptor (GPCR) galanin-receptor 2 (GALR2) that alters an important amino acid in the TM6 molecular toggle switch region (W249L). Nuclear magnetic resonance imaging showed that the hypothalamus (an area rich in GALR2) of this patient exhibited an important volumetric reduction leading to an enlarged third ventricle. Ex vivo experiments with patient-derived blood cells (AKT phosphorylation), as well as studies in recombinant cell lines expressing the human GALR2 (calcium mobilization and NFAT mediated gene transcription), showed that galanin (GAL) was unable to stimulate cell signaling in cells expressing the variant GALR2 allele. Live cell confocal microscopy showed that the GALR2 mutant receptor was primarily localized to intracellular endosomes. We conclude that the W249L SNV is likely to abrogate GAL-mediated signaling through GALR2 due to the spontaneous internalization of this receptor in this patient. Although this homozygous SNV was rare in our MS cohort (1:262 cases), our findings raise the potential importance of impaired neuroregenerative pathways in the pathogenesis of MS, warrant future studies into the relevance of the GAL/GALR2 axis in MS and further suggest the activation of GALR2 as a potential therapeutic route for this disease.

Made available in DSpace on 2018-12-11T17:23:08Z (GMT). No. of bitstreams: 0 Previous issue date: 2016-08-01 High dose immunosuppression followed by autologous hematopoietic stem cell transplantation (AHSCT) induces prolonged clinical remission in multiple sclerosis (MS) patients. However, how patient immune profiles are associated with clinical outcomes has not yet been completely elucidated. In this study, 37 MS patients were assessed for neurological outcomes, thymic function and long-term immune reconstitution after AHSCT. Patients were followed for a mean (SD) of 68.5 (13.9) months post-transplantation and were retrospectively clustered into progression- and non-progression groups, based on Expanded Disease Status Scale (EDSS) outcomes at last visit. After AHSCT, both patient groups presented increased regulatory T-cell subset counts, early expansion of central- and effector-memory CD8+ T-cells and late thymic reactivation. However, the non-progression group presented early expansion of PD-1+CD8+ T-cells and of PD-1-expressing CD19+ B-cells. Here, we suggest that along with increased numbers of regulatory T-cell subsets, PD-1 inhibitory signaling is one possible immunoregulatory mechanism by which AHSCT restores immune tolerance in MS patients. Center for Cell-based Therapy Regional Blood Center of Ribeir�o Preto Ribeir�o Preto Medical School University of S�o Paulo Department of Biochemistry and Immunology Ribeir�o Preto Medical School University of S�o Paulo Department of Neuroscience and Behavioral Science Ribeir�o Preto Medical School University of S�o Paulo Department of Internal Medicine Ribeir�o Preto Medical School University of S�o Paulo Universidade Estadual Paulista UNESP Department of Clinical Toxicological and Bromatological Analysis School of Pharmaceutical Sciences of Ribeir�o Preto University of S�o Paulo Universidade Estadual Paulista UNESP

The hereditary neuropathy with liability to pressure palsies (HNPP) is an autossomal dominant disorder manifesting recurrent mononeuropathies. Objective Evaluate its clinical and nerve conduction studies (NCS) characteristics, searching for diagnostic particularities. Method We reviewed the neurological manifestations of 39 and the NCS of 33 patients. Results Family history was absent in 16/39 (41%). The onset complaints were weakness in 24, pain in 6, sensory deficit in 5 and paresthesias in 4. Pain was seen in 3 other patients. The following neuropathy patterns were found: multiple mononeuropathy (26), mononeuropathy (7), chronic sensorimotor polyneuropathy (4), chronic sensory polyneuropathy (1) and unilateral brachial plexopathy (1). NCS showed a sensorimotor neuropathy with focal conduction slowing in 31, two had mononeuropathy and another brachial plexopathy. Conclusion HNPP presentation is variable and may include pain. The most frequent pattern is of an asymmetrical sensory and motor neuropathy with focal slowing at specific topographies on NCS. RESUMO A neuropatia hereditária com susceptibilidade à pressão (HNPP) é uma doença autossômica dominante que manifesta mononeuropatias recorrentes. Objetivo Avaliar as características clínicas e os estudos da condução nervosa (ECN) procurando particularidades diagnósticas. Método Revisamos as características clínicas de 39 e os ECN de 33 pacientes. Resultados História familiar ausente em 16/39 (41%). As manifestações iniciais foram: fraqueza em 24, dor em 6, déficit sensitivo em 5 e parestesias em 4. Dor foi referida por outros 3 pacientes. Os seguintes padrões de neuropatia foram observados: mononeuropatia múltipla (26), mononeuropatia (6), polineuropatia sensitivo-motora (4), polineuropatia sensitiva (1) e plexopatia braquial unilateral (1). Os ECN mostraram uma neuropatia sensitivo-motora com redução focal da velocidade de condução em 31, dois tinham mononeuropatia e outro plexopatia braquial. Conclusão A apresentação da HNPP é variável e pode incluir dor. O padrão mais frequente é o de uma neuropatia sensitivo-motora assimétrica com alentecimentos focais da condução em topografias específicas nos ECN.

Background Fampridine is a broad-spectrum voltage-dependent potassium channel blocker that enhances synaptic transmission. The drug has been shown to be able to ameliorate conduction in demyelinated axons, thereby leading to improved gait in patients with multiple sclerosis (MS). Objective To assess the "real-life" efficacy and safety of fampridine prescribed for gait disorders in MS. This was an observational and prospective study carried out at MS Units participating in the Brazilian Multiple Sclerosis Study Group. Methods Patients with MS and gait disorders were prescribed fampridine (10 mg twice a day), irrespectively of the degree of disability determined by MS. Neurological disability determined by MS was assessed with the expanded disability scale score (EDSS). Outcomes for efficacy and safety of the drug were evaluated by the 25 foot-walk test and by the adverse events of fampridine. Results The time taken to walk 25 feet decreased by 20% or more in 62 patients (70%). Twenty-five patients were considered to be non-responders to this treatment. Improvement in walking speed was independent of improvement of disability. Mild or moderate adverse events were reported in 8% of patients. Conclusion Fampridine is an efficient and safe therapeutic option for patients with MS and gait disorders.

Background There have been no clinical trials for approval of medications for treating multiple sclerosis in patients younger than age 18 years. All treatments are based on personal experience and data from open observational studies. Fingolimod is an oral drug for multiple sclerosis that has been shown to be efficient and safe in adults. The aim of our study is to describe patients with multiple sclerosis who started treatment with fingolimod before the age of 18 years. Participants and methods Seventeen patients treated with fingolimod were identified in the Brazilian database of children and adolescents with multiple sclerosis. The average time of use of the drug was 8.6 months. Results Fingolimod showed a good safety and efficacy profile in these patients, all of whom had very active multiple sclerosis. After starting treatment with fingolimod, only one patient had a relapse and a new lesion on magnetic resonance imaging. The patients' degree of disability did not progress. No major adverse events were reported in relation to the first dose of the drug, nor in the short- and medium-term treatment. No patient has been followed for longer than 18 months, thus limiting long-term conclusions. Conclusions Off-label use of fingolimod in patients younger than age 18 years may be a good therapeutic option for multiple sclerosis control.

The familial amyloidotic polyneuropathies (FAP) are autosomal dominant, length-dependent, axonal neuropathies first described in Portugal in 19581. They were later shown to be heterogeneous, resulting from tissue deposition of abnormal variants of physiological proteins, including transthyretin (TTR), apolipoprotein-A1 and gelsolin1,2 […] Clinical and electrophysiological correlates of TTRala71 amyloid neuropathy

Uniform conduction slowing has been considered a characteristic of inherited demyelinating neuropathies. We present an 18-year-old girl, born from first cousins, that presented a late motor and psychological development, cerebellar ataxia, facial diplegia, abnormal eye movement, scoliosis, and corpus callosum agenesis, whose compound muscle action potentials were slowed and dispersed. A mutation was found on KCC3 gene, confirming Andermann syndrome, a disease that must be included in the differential diagnosis of inherited neuropathies with non-uniform conduction slowing.

The spinal muscular atrophies (SMA) or hereditary motor neuronopathies result from the continuous degeneration and death of spinal cord lower motor neurons, leading to progressive muscular weakness and atrophy. We describe a large Brazilian family exhibiting an extremely rare, late-onset, dominant, proximal, and progressive SMA accompanied by very unusual manifestations, such as an abnormal sweating pattern, and gastrointestinal and sexual dysfunctions, suggesting concomitant involvement of the autonomic nervous system. We propose a new disease category for this disorder, 'hereditary motor and autonomic neuronopathy', and attribute the term, 'survival of motor and autonomic neurons 1' (SMAN1) to the respective locus that was mapped to a 14.5 cM region on chromosome 20q13.2-13.3 by genetic linkage analysis and haplotype studies using microsatellite polymorphic markers. This locus lies between markers D20S120 and D20S173 showing a maximum LOD score of 4.6 at D20S171, defining a region with 33 known genes, including several potential candidates. Identifying the SMAN1 gene should not only improve our understanding of the molecular mechanisms underlying lower motor neuron diseases but also help to clarify the relationship between motor and autonomic neurons.

Embasamento: A Esclerose Múltipla (EM) é uma doença desmielinizante inflamatória restrita ao sistema nervoso central, caracterizada pela ocorrência de inflamação focal com distribuição perivenular. Os critérios diagnósticos da doença foram revisados em 2017, sendo conhecidos como critérios de McDonald e se baseiam nos princípios de dissociação temporal e espacial das lesões. Apesar de ser conhecido que a doença acomete virtualmente qualquer porção do SNC, sendo predominante na substância branca (SB), porém, não exclusiva, envolvendo também córtex e substância cinzenta (SC) profunda. A identificação de recorrência da doença se baseia na identificação de focos macroscópicos de desmielinização, conhecidos como placas. In vivo, o diagnóstico das placas depende da sua identificação em exames de imagem ressonância magnética (MRI). Os pacientes com EM são submetidos a exames de MRI do encéfalo com o intuito de se identificar lesões novas ou aumento do volume total de lesões. A lesão aparece no exame de MRI como uma imagem de hiperintensidade de sinal em sequências T2, que pode ser isolada, medindo mais que 3 a 5 mm, ovaladas, com realce após administração de contraste paramagnético intravenoso na fase aguda. Cronicamente as placas se tornam menos delimitáveis, coalescentes, formando aglomerados dismórficos com predomínio no corpo caloso e região de SB periventricular. A detecção de novas lesões entre dois exames de MRI é critério para a definição de estabilidade ou progressão de doença, bem como o sucesso ou fracasso terapêutico. Em pacientes com alta carga lesional, a detecção de uma nova e pequena lesão não é tarefa trivial para o médico radiologista. Objetivo: Para aumentar a sensibilidade e especificidade do exame é a proposta deste trabalho o desenvolvimento de um algoritmo computacional para volumetria de lesões e comparação entre diferentes tempos de estudo a fim de identificar lesões novas. Casuística e Método: Foram analisadas retrospectivamente as imagens de 99 pacientes com diagnóstico confirmado de Esclerose Múltipla e acompanhados clinicamente no HCFMRP-USP no período de 2013 a 2020 com imagens adquiridas um equipamento de 3T (Philips, Achieva). A imagem volumétrica FLAIR de dois exames consecutivos foram segmentadas e corregistradas. Uma ferramenta para detecção de novas lesões foi implementada, comparando exames prévios e recentes por software de detecção automática de lesões. Resultados: Foi observada uma sensibilidade de 95% e especificidade de 31%. Somente houve um falso negativo entre os 99 exames avaliados. Conclusão: o algoritmo desenvolvido foi considerado efetivo, com alta sensibilidade e funcionando de forma totalmente automática. A prática diária demonstrou que houve um auxílio real na rotina de avaliação dos exames, aumentando a rapidez e confiabilidade da avaliação. A baixa especificidade não compromete a eficiência, sendo os falsos positivos rapidamente descartados pelo médico radiologista. Background: Multiple Sclerosis (MS) is an inflammatory demyelinating disease restricted to the central nervous system, characterized by the occurrence of focal inflammation with perivenular distribution. The diagnostic criteria for the disease were revised in 2017, known as McDonald\'s criteria and are based on the principles of temporal and spatial dissociation of injuries. Although it is known that the disease affects virtually any portion of the CNS, being predominant in white matter (SB), however, not exclusive, also involving cortex and deep gray matter (SC). The identification of disease recurrence is based on the identification of macroscopic foci of demyelination, known as plaques. In vivo, the diagnosis of plaques depends on their identification in magnetic resonance imaging (MRI) exams. Patients with MS are submitted to brain MRI exams in order to identify new lesions or increase the total lesion volume. The lesion appears on the MRI exam as an image of signal hyperintensity in T2 sequences, which can be isolated, measuring more than 3 to 5 mm, oval, with enhancement after intravenous paramagnetic contrast in the acute phase. Chronically, the plaques become less delimitable, coalescent, forming dysmorphic clusters with predominance in the corpus callosum and periventricular SB region. The detection of new lesions between two MRI exams is a criterion for defining disease stability or progression, as well as therapeutic success or failure. In patients with a high lesion load, the detection of a new and small lesion is not a trivial task for the radiologist. Objective: To increase the sensitivity and specificity of the exam, the purpose of this work is to develop a computational algorithm for lesion volumetry and to compare different study times in order to identify new lesions. Casuistic and Method: The images of 99 patients with confirmed diagnosis of Multiple Sclerosis were retrospectively analyzed and followed up clinically at HCFMRP-USP in the period from 2013 to 2020 with images acquired from a 3T equipment (Philips, Achieva). The volumetric FLAIR image of two consecutive exams was segmented and registered. A tool for detecting new injuries was implemented, comparing previous and recent exams using automatic injury detection software. Results: A sensitivity of 95% and specificity of 31% were observed. There was only one false negative among the 99 tests evaluated. Conclusion: the developed algorithm was considered effective, with high sensitivity and working in a fully automatic way. Daily practice demonstrated that there was a real help in the routine of exam assessment, increasing the speed and reliability of the assessment. Low specificity does not compromise efficiency, and false positives are quickly discarded by the radiologist.

A Esclerose Múltipla (EM) é uma patologia caracterizada pela presença de lesões desmielinizantes no sistema nervoso central (SNC), multifatorial, que afeta cerca de 2-3 milhões de pessoas no mundo e que acarreta grande impacto na funcionalidade e qualidade de vida desses pacientes (18). Múltiplas possíveis causas se correlacionam com essa condição como meio ambiente, fatores genéticos e epigenéticos que potencialmente interagem com fatores de risco modificáveis com obesidade, fumo, dieta e deficiência de vitamina D. Do ponto de vista imunológico, os estudos mostram que o sistema imunológico adaptativo é a peça chave na patogênese da EM. Acredita-se que as células T e C são recrutadas por antígenos específicos do SNC levando à perda axono-neuronal, desmielinização e gliose (18). Na prática clínica, a maioria dos pacientes são submetidos a Ressonâncias Magnéticas (RM) contrastadas para controle radiológico da doença, o que causa preocupação tendo em vista que estudos recentes demonstram o aumento de sinal espontâneo T1W (sequências ponderadas em T1) no globo pálido (GP) e núcleo denteado (ND) em pacientes submetidos a injeções repetidas de meio de contraste a base de gadolínio (Gd) (2,5,8). Objetivo: Correlacionar o aumento da intensidade de sinal na sequência T1 pré-contraste no globo pálido e núcleo denteado em pacientes com EM e sua relação com a injeções repetidas de meio de contraste a base de gadolíneo. Método: Foram analisados retrospectivamente, os casos de 100 pacientes acompanhados no HCFMRP-USP com diagnóstico de esclerose múltipla, no período de 2013 a 2018 e de 61 casos de pacientes normais que foram utilizados como grupo controle, os quais nunca foram submetidos a estudos com contraste paramagnético até aquele momento, cujos exames foram realizados na mesma instituição no período de 2009 a 2013. A análise das imagens de RM foi realizada por dois observadores independentes, que avaliaram a sequência volumétrica T1W e constataram ou não visualmente o aumento da intensidade de sinal no globo pálido (GP) e núcleo denteado(ND) em relação ao tálamo ( T) e ponte (P), respectivamente, utilizando o programa Osirix (Pixmeo - Genebra - Suiça). Após essa análise, foi realizada de maneira automatizada a relação da intensidade de sinal entre o GP/T e ND/P de maneira, após padronização em plataforma Standard. Resultados: Não houve diferença estatisticamente significativa (p < 0,05) entre o aumento da intensidade de sinal GP/T e ND/P nos pacientes do grupo teste e do grupo controle. A única diferença significativa entre os grupos se deu na variável idade (p= 0,004), notando-se aumento dessas relações no grupo de pacientes doentes. Conclusão: O aumento da intensidade de sinal do GP e do ND é objeto de estudo recente na literatura, com trabalhos mostrando correlação entre o aumento dos mesmos e o número de exames com uso do Gadolínio. Este estudo não confirmou esse achado, o que leva ao questionamento se os pacientes encurtam o sinal T1W com o uso repetido do gadolínio ou se o mesmo é ocasionado pela degeneração progressiva resultante da doença de base (EM), hipóteses que necessitam ser testadas através de estudos futuros. Multiple sclerosis (MS) is a pathology characterized by the presence of demyelinating lesions in the central nervous system (CNS), multifactorial, which affects about 2-3 million people worldwide and has a great impact on the functionality and quality of life of these patients. (18). Multiple possible causes correlate with this condition such as the environment, genetic and epigenetic factors that potentially interact with modifiable risk factors with obesity, smoking, diet and vitamin D deficiency. From an immunological point of view, studies show that the adaptive immune system it is the key piece in the pathogenesis of MS. It is believed that T and C cells are recruited by specific CNS antigens leading to axono-neuronal loss, demyelination and gliosis (18). In clinical practice, most patients are submitted to contrasted magnetic resonance imaging (MRI) for radiological control of the disease, which is a cause for concern since recent studies demonstrate an increase in spontaneous T1W signal (T1-weighted sequences) in the pale globe ( GP) and dentate core (ND) in patients undergoing repeated injections of gadolinium-based contrast medium (Gd) (2,5,8). Objective: Correlate the increase in signal intensity in the pre-contrast T1 sequence in the pale globe and dentate nucleus in patients with MS and its relationship with repeated injections of gadolinium-based contrast medium. Methods: We retrospectively analyzed the cases of 100 patients followed up at HCFMRP-USP with a diagnosis of multiple sclerosis, from 2013 to 2018 and 61 cases of normal patients who were used as a control group, who were never submitted to studies with paramagnetic contrast until that moment, whose exams were performed at the same institution from 2009 to 2013. The analysis of MRI images was performed by two independent observers, who evaluated the T1W volumetric sequence and whether or not they visually verified the increase in signal intensity. in the pale globe (GP) and dentate nucleus (ND) in relation to the thalamus (T) and bridge (P), respectively, using the Osirix program (Pixmeo - Geneva - Switzerland). After this analysis, the signal intensity relationship between the GP / T and ND / P was performed in an automated manner, after standardization on a Standard platform. Results: There was no statistically significant difference (p

Tremor essencial é uma síndrome de tremor de ação de membros superiores com duração de ao menos 3 anos, que pode vir acompanhada de tremor em outras localizações e de outros sinais neurológicos sutis. Por muito tempo considerado benigno, sua associação a sintomas não motores e a doenças neurodegenerativas foi demonstrada na literatura. Ademais, ganha força a percepção de heterogeneidade no comportamento da doença, com características distintas entre pacientes com início do tremor precoce e tardio. É conhecido um aumento no risco de Doença de Parkinson entre os pacientes com Tremor Essencial. O diagnóstico da Doença de Parkinson é fundado em sintomas motores, sendo reconhecida uma fase prodrômica da doença, para a qual foram publicados critérios diagnósticos baseados em fatores de risco da doença e em marcadores prodrômicos. No entanto, carece na literatura maior exploração do comportamento da fase prodrômica da Doença de Parkinson e de seus sintomas em pacientes com Tremor Essencial. Objetivo: Avaliar e comparar a prevalência de fatores de risco e marcadores prodrômicos da Doença de Parkinson e realizar o diagnóstico de sua fase prodrômica em grupos de pacientes idosos com Tremor Essencial de início tardio e de início precoce, avaliando se pacientes com TE de início tardio apresentarão maior prevalência de sintomas e de Doença de Parkinson prodrômica. Método: Realizado estudo transversal analítico tipo caso-controle, no qual foram incluídos pacientes em seguimento no Ambulatório de Doenças Extrapiramidais do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto com diagnóstico de Tremor Essencial e Tremor Essencial Plus com idade a partir dos 60 anos, sem parkinsonismo e com desempenho cognitivo dentro dos padrões normatizados no Mini Exame do Estado Mental. 43 pacientes foram divididos em dois grupos, um de pacientes com Tremor Essencial de início precoce (antes dos 60 anos) e outro de pacientes com início tardio dos sintomas (após os 60 anos). Os grupos foram compostos, respectivamente, por 30 e por 13 pacientes. Foi realizada avaliação para coleta de dados sociodemográficos, clínicos gerais e quanto à presença de fatores de risco e marcadores prodrômicos da Doença de Parkinson. Os dados foram posteriormente analisados quanto à presença de Doença de Parkinson prodrômica de acordo com metodologia proposta pela Movement Disorders Society. Resultados: O grupo de pacientes com Tremor Essencial de início tardio foi composto de pacientes mais velhos (p=0,039) com menor tempo de duração média do tremor (p