Pablo Brea Winckler

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an acquired autoimmune disorder that leads to progressive motor and sensory impairment, resulting in significant morbidity. While the incidence rates vary, CIDP remains a challenging condition requiring a standardized and optimized approach to diagnosis and management. In Brazil, a middle-income country with substantial regional disparities in healthcare access, the availability of specialized neuromuscular centers is uneven, creating obstacles to timely and effective treatment. To address these challenges, the Brazilian Academy of Neurology (Academia Brasileira de Neurologia, ABN, in Portuguese) has developed national recommendations for the diagnosis, management, and treatment of CIDP, tailored to the country's healthcare resources. This consensus outlines standardized diagnostic criteria that incorporate electrophysiological and imaging findings, and it emphasizes key differential diagnoses to enhance diagnostic accuracy. The recommendations were developed through expert panel discussions and a non-systematic review of the literature. The recommended treatment strategies include first-line therapies such as corticosteroids, intravenous immunoglobulin (IVIg), and plasmapheresis, with guidance on escalation and titration of immunosuppressive therapy in refractory cases. By emphasizing early intervention to prevent axonal degeneration and disability, these guidelines aim to improve clinical outcomes and support public health policies within the Brazilian National Health System (Sistema Único de Saúde, SUS, in Portuguese), ensuring equitable and effective CIDP management across the country.

Background Epilepsy surgery is recognized for its effectiveness in controlling seizures in a significant number of patients with drug-resistant epilepsy. Despite this, there remains a notable deficiency in referring these patients for video-electroencephalogram (EEG) monitoring and surgical evaluation. Addressing this gap, the Canadian Appropriateness of Epilepsy Surgery (CASES), an online tool for epilepsy surgery evaluation (www.epilepsycases.com), was developed to aid physicians in the referral process of patients with refractory epilepsy to surgical assessments. Objective The present study aimed to evaluate the utility of CASES in identifying candidates for epilepsy surgery, thereby facilitating clinical decision-making for patients with drug-resistant epilepsy. Methods A cross-sectional analysis was conducted using the CASES platform to assess surgical candidacy among individuals with epilepsy. Participants were selected among those receiving care at the Epilepsy Clinic of the Neurology Service, Hospital de Clínicas de Porto Alegre, Brazil, over a 3-month period. The study cohort included 211 patients. Data were systematically extracted from patient medical records or collected during clinical appointments. Results Of the evaluated cohort, 59.6% were identified as potential candidates for video-EEG monitoring and subsequent surgical evaluation. Factors significantly associated with recommendations for video-EEG and surgical assessment included seizure frequency, the number of antiseizure medications (ASMs) trialed, and the occurrence of drug-related adverse effects. Conclusion The CASES showed significant potential in guiding recommendations for video-EEG monitoring and facilitating referrals for epilepsy surgery. This tool may not only enhance patient treatments and outcomes but also contribute to cost savings in epilepsy management in both the short and long term.

Introduction: The Hereditary Spastic Paraplegias (HSP) are a group of genetic diseases that lead to slow deterioration of locomotion. Clinical scales seem to have low sensitivity in detecting disease progression, making the search for additional biomarkers a paramount task. This study aims to evaluate the role of evoked potentials (EPs) as disease biomarkers of HSPs. Methods: A single center cross-sectional case-control study was performed, in which 18 individuals with genetic diagnosis of HSP and 21 healthy controls were evaluated. Motor evoked potentials (MEP) obtained with transcranial magnetic stimulation and somatosensory evoked potentials (SSEP) were performed in lower (LL) and upper limbs (UL). Results: Central motor conduction time in lower limbs (CMCT-LL) was prolonged in HSP subjects, with marked reductions in MEP-LL amplitudes when compared to the control group (p<0.001 for both comparisons). CMCT-UL was 3.59ms (95% CI: 0.73 to 6.46; p = 0.015) prolonged and MEP-UL amplitudes were reduced (p = 0.008) in the HSP group. SSEP-LL latencies were prolonged in HSP subjects when compared to controls (p<0.001), with no statistically significant differences for upper limbs (p = 0.147). SSEP-UL and SSEP-LL latencies presented moderate to strong correlations with age at onset (Rho = 0.613, p = 0.012) and disease duration (Rho = 0.835, p<0.001), respectively. Similar results were obtained for the SPG4 subgroups of patients. Conclusion: Motor and somatosensory evoked potentials can adequately differentiate HSP individuals from controls. MEP were severely affected in HSP subjects and SSEP-LL latencies were prolonged, with longer latencies being related to more severe disease. Future longitudinal studies should address if SSEP is a sensitive disease progression biomarker for HSP.

Myasthenia Gravis (MG) is an autoimmune disease. The characteristic symptoms of the disease are muscle weakness and fatigue. These symptoms affect de oral muscles causing dysarthria, affecting abou...

We investigated the cognitive performance of patients with Myasthenia Gravis (MG) through a cross-sectional study. A battery of cognitive assessments and self-report questionnaires regarding quality of life (QoL), sleep, and depression were applied. The sample consisted of 39 patients diagnosed with MG. The scores showed a predominance of cognitive impairment in the Montreal Cognitive Assessment screening test (MoCA) (66.7%) and in the immediate (59.0%) and recent memory (56.4%) tests. However, after the Poisson regression analysis with robust variance, it was found that patients diagnosed with depression had a prevalence ratio (PR) of 1,887 (CI 1,166‒3,054) for lower MoCA scores, PR=9,533 (CI 1,600‒56,788) for poorer phonemic verbal fluency scores, and PR=12,426 (CI 2,177‒70,931) for the Semantic Verbal Fluency test. Moreover, concerning a decline in short-term memory retention, patients using glucocorticosteroids (GC) and with Beck Depression Inventory scores indicating depression showed PR=11,227 (CI 1,736‒72,604) and PR=0.35 (CI 0.13‒0.904), respectively. No correlation was found between the QoL questionnaire and performance in cognitive tests. We found worse performance in tasks of memory and executive functions in MG patients. These are not associated with the length and severity of the disease. However, a significant prevalence ratio was found for poorer memory performance in patients diagnosed with depression and in those using GC.

Diagnostic yield of genetic studies for Charcot‐Marie‐Tooth disease (CMT) is little known, with a lack of epidemiological data to build better diagnostic strategies outside the United States and Europe. We aimed to evaluate the performance of two molecular diagnostic strategies for patients with CMT, and to characterize epidemiological findings of these conditions in southern Brazil. We performed a single‐center cross‐sectional study, in which 94 patients (55 families) with CMT suspicion were evaluated. Overall, the diagnostic yield of the combined strategy of Multiplex‐ligation‐dependent‐probe‐amplification (MLPA) of PMP22/GJB1/MPZ and GJB1/MPZ/PMP22 Sanger sequencing was 63.6% (28/44) for index cases with demyelinating/intermediate CMT suspicion (21 CMT1A‐PMP22, 5 CMTX1‐GJB1 and 2 with probably CMT1B‐MPZ diagnosis). Five of the 11 index cases (45.4%) with axonal CMT had at least a possible diagnosis with next generation sequencing (NGS) panel of 104 inherited neuropathies‐related genes (one each with CMT1A‐PMP22, CMT2A‐MFN2, CMT2K‐GDAP1, CMT2U‐MARS, CMT2W‐HARS1). Detailed clinical, neurophysiological and molecular data of families are provided. Sequential molecular diagnosis strategies with MLPA plus target Sanger sequencing for demyelinating/intermediate CMT had high diagnostic yield, and almost half of axonal CMT families had at least a possible diagnosis with the comprehensive NGS panel. Most frequent subtypes of CMT in our region are CMT1A‐PMP22 and CMTX1‐GJB1.

Limb‐girdle muscular dystrophies (LGMD) are a group of genetically heterogeneous disorders characterized by predominantly proximal muscle weakness. We aimed to characterize epidemiological, clinical and molecular data of patients with autosomal recessive LGMD2/LGMD‐R in Brazil. A multicenter historical cohort study was performed at 13 centers, in which index cases and their affected relatives' data from consecutive families with genetic or pathological diagnosis of LGMD2/LGMD‐R were reviewed from July 2017 to August 2018. Survival curves to major handicap for LGMD2A/LGMD‐R1‐calpain3‐related, LGMD2B/LGMD‐R2‐dysferlin‐related and sarcoglycanopathies were built and progressions according to sex and genotype were estimated. In 370 patients (305 families) with LGMD2/LGMD‐R, most frequent subtypes were LGMD2A/LGMD‐R1‐calpain3‐related and LGMD2B/LGMD‐R2‐dysferlin‐related, each representing around 30% of families. Sarcoglycanopathies were the most frequent childhood‐onset subtype, representing 21% of families. Five percent of families had LGMD2G/LGMD‐R7‐telethonin‐related, an ultra‐rare subtype worldwide. Females with LGMD2B/LGMD‐R2‐dysferlin‐related had less severe progression to handicap than males and LGMD2A/LGMD‐R1‐calpain3‐related patients with truncating variants had earlier disease onset and more severe progression to handicap than patients without truncating variants. We have provided paramount epidemiological data of LGMD2/LGMD‐R in Brazil that might help on differential diagnosis, better patient care and guiding future collaborative clinical trials and natural history studies in the field.

Objective: ANO5‐related myopathy is an important cause of limb‐girdle muscular dystrophy (LGMD) and hyperCKemia. The main descriptions have emerged from European cohorts, and the burden of the disease worldwide is unclear. We provide a detailed characterization of a large Brazilian cohort of ANO5 patients.Methods: A national cross‐sectional study was conducted to describe clinical, histopathological, radiological, and molecular features of patients carrying recessive variants in ANO5. Correlation of clinical and genetic characteristics with different phenotypes was studied.Results: Thirty‐seven patients from 34 nonrelated families with recessive mutations of ANO5 were identified. The most common phenotype was LGMD, observed in 25 (67.5%) patients, followed by pseudometabolic presentation in 7 (18.9%) patients, isolated asymptomatic hyperCKemia in 4 (10.8%) patients, and distal myopathy in a single patient. Nine patients presented axial involvement, including one patient with isolated axial weakness. The most affected muscles according to MRI were the semimembranosus and gastrocnemius, but paraspinal and abdominal muscles, when studied, were involved in most patients. Fourteen variants in ANO5 were identified, and the c.191dupA was present in 19 (56%) families. Sex, years of disease, and the presence of loss‐of‐function variants were not associated with specific phenotypes.Interpretation: We present the largest series of anoctaminopathy outside Europe. The most common European founder mutation c.191dupA was very frequent in our population. Gender, disease duration, and genotype did not determine the phenotype.