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Cerebrotendinous xanthomatosis (CTX) is a rare metabolic disorder caused by mutations in the CYP27A1 gene, leading to cholestanol accumulation in various tissues, including peripheral nerves. Polyneuropathy is an underrecognized feature with considerable variability in clinical presentation and neurophysiological findings in CTX. This review assesses the prevalence, clinical manifestations, and diagnostic methodologies of polyneuropathy in CTX, exploring its underlying mechanisms and potential treatment outcomes. A literature review was conducted using PubMed, Embase, and the Virtual Health Library databases with search terms related to CTX and polyneuropathy. A total of 892 articles were initially identified, with 59 selected for in-depth analysis. The review focused on studies examining peripheral nerve involvement in CTX, including nerve conduction studies, electromyography, and nerve ultrasound. Polyneuropathy in CTX was observed in 50% to 77.7% of patients across multiple case series. Neurophysiological findings varied, with reports of axonal, demyelinating, and mixed polyneuropathies. Clinical presentation included lower limb atrophy, pes cavus, and distal weakness, with sensory symptoms less frequently reported. Treatment with chenodeoxycholic acid (CDCA) showed potential in improving nerve conduction parameters, although the response was variable and dependent on the timing of intervention. Polyneuropathy in CTX presents significant diagnostic challenges due to its heterogeneous presentation and varying neurophysiological findings. Early recognition and intervention are crucial for improving patient outcomes. Peripheral nerve ultrasound is a promising diagnostic tool, complementing traditional neurophysiological assessments. Further research is needed to standardize protocols and explore the full therapeutic potential of CDCA in managing CTX-related polyneuropathy. [ABSTRACT FROM AUTHOR]

Dystrophinopathies are muscle diseases caused by pathogenic variants in DMD, the largest gene described in humans, representing a spectrum of diseases ranging from asymptomatic creatine phosphokinase elevation to severe Duchenne muscular dystrophy (DMD). Several therapeutic strategies are currently in use or under development, each targeting different pathogenic variants. However, little is known about the genetic profiles of northeast Brazilian patients with dystrophinopathies. We describe the spectrum of pathogenic DMD variants in a single center in northeast Brazil. This is an observational, cross-sectional study carried out through molecular-genetic analysis of male patients diagnosed with dystrophinopathies using Multiplex Ligation-dependent Probe Amplification (MLPA) followed by Next-Generation Sequencing (NGS)-based strategies. A total of 94 male patients were evaluated. Deletions (43.6%) and duplications (10.6%) were the most recurring patterns of pathogenic variants. However, small variants were present in 47.1% of patients, most of them nonsense variants (27.6%). This is the largest South American single-center case series of dystrophinopathies to date. We found a higher frequency of treatment-amenable nonsense single-nucleotide variants than most previous studies. These findings may have implications for diagnostic strategies in less-known populations, as a higher frequency of nonsense variants may mean a higher possibility of treating patients with disease-modifying drugs. [ABSTRACT FROM AUTHOR]

The letter to the editor discusses a case of slowly progressive amyotrophic lateral sclerosis (ALS) in a Brazilian family with a homozygous p.Val120Leu (c.358G > C) SOD1 mutation. The patient described in the letter was tetraparetic six years after disease onset, while another patient from the same region with heterozygosis for the same mutation had a very slowly progressive disease, still able to walk independently 21 years after onset. The report highlights the milder phenotype associated with this SOD1 variant in a monoallelic state, emphasizing the need for further studies to assess the frequency of ALS due to this variant in northeast Brazil. [Extracted from the article]

Hereditary Ataxias (HAs) comprise a wide spectrum of genetically determined neurodegenerative diseases with progressive ataxia as the main symptom. Few studies have evaluated nutritional profile in HA patients and most of these focused on specific ataxia subtypes. The objectives of this study were: (1) to investigate whether hereditary ataxias were associated with changes in energy expenditure, body composition and dietary intake; (2) to verify differences in these variables according to ataxia subtype, sex, age, and disease severity. Thirty-eight hereditary ataxia patients from two neurology centers in Northeastern Brazil and 38 controls were evaluated. Body composition was assessed with bio-impedance analysis and dietary intake was estimated with a validated questionnaire (24-hour dietary recall). Mean body mass index (BMI) was lower in HA compared to controls (p = 0.032). Hereditary ataxia patients showed lower protein intake, higher frequency of dysphagia and higher incidence of nausea and diarrhea. The difference in average estimated caloric intake did not reach statistical significance (2359kcal ± 622 in patients × 2713kcal ± 804 in controls, p = 0.08). Disease severity measured by the SARA scale was not associated with BMI, nor was ataxia subtype (autosomal dominant × non-autosomal dominant ataxias). Hereditary ataxia patients have lower BMI compared to healthy controls. There was no difference in this cohort between dominant or non-dominant ataxia regarding BMI. Weight loss may be a common finding among hereditary ataxias and may affect the quality of life in these patients. [ABSTRACT FROM AUTHOR]

Background: Congenital myopathy-13 (CMYP13), also known as Bailey-Bloch congenital myopathy and Native American myopathy (NAM), is a condition caused by biallelic missense pathogenic variants in STAC3, which encodes an important protein necessary for the excitation-relaxation coupling machinery in the muscle. Patients with biallelic pathogenic variants in STAC3 often present with congenital weakness and arthrogryposis, cleft palate, ptosis, myopathic facies, short stature, kyphoscoliosis, and susceptibility to malignant hyperthermia provoked by anesthesia. We present two unrelated cases of Bailey-Bloch congenital myopathy descendants of non-consanguineous parents, which were investigated for delayed psychomotor development and generalized weakness. To the best of our knowledge, these are the first descriptions of CMYP13 in Brazil. In both patients, we found the previously described pathogenic missense variant p.Trp284Ser in homozygosity. Conclusion: We seek to highlight the need for screening for CMYP13 in patients expressing the typical phenotype of the disease even in the absence of Lumbee Native American ancestry, and to raise awareness to possible complications like malignant hyperthermia in Bailey-Bloch congenital myopathy. [ABSTRACT FROM AUTHOR]

Biallelic loss of function of IMPA1 causes autosomal recessive intellectual developmental disorder 59 (MRT59, OMIM #617323). MRT59 has been reported to present with significant intellectual disability and disruptive behavior, but little is known about the neurocognitive pattern of those patients. Thus, the aims of this study were: (1) to assess the cognitive profile of these patients, and (2) to evaluate their functional dependence levels. Eighteen adults, aged 37 to 89 years, participated in this study: nine MRT59 patients, five heterozygous carriers and four non-carrier family members. All of them were from a consanguineous family living in Northeast Brazil. All IMPA1 patients had the (c.489_493dupGGGCT) pathogenic variant in homozygosis. For cognitive assessment, the WASI battery was applied in nine MRT59 patients and compared to heterozygous carriers and non-carrier family members. Functional dependence was evaluated using the functional independence measure (FIM). Patients showed moderate to severe intellectual disability and severe functional disabilities. Heterozygous carriers did not differ from non-carriers. MRT59 patients should be followed up by health professionals in an interdisciplinary way to understand their cognitive disabilities and functional needs properly. [ABSTRACT FROM AUTHOR]

Cerebrotendinous xanthomatosis (CTX) is an autosomal recessive disorder caused by pathogenic variants in CYP27A1, leading to a deficiency in sterol 27-hydroxylase. This defect results in the accumulation of cholestanol and bile alcohols in various tissues, including the brain, tendons and peripheral nerves. We conducted this review to evaluate lipid profile abnormalities in patients with CTX. A search was conducted in PubMed, Embase and the Virtual Health Library in January 2023 to evaluate studies reporting the lipid profiles of CTX patients, including the levels of cholestanol, cholesterol and other lipids. Elevated levels of cholestanol were consistently observed. Most patients presented normal or low serum cholesterol levels. A decrease in chenodeoxycholic acid (CDCA) leads to increased synthesis of cholesterol metabolites, such as bile alcohols 23S-pentol and 25-tetrol 3-glucuronide, which may serve as surrogate follow-up markers in patients with CTX. Lipid abnormalities in CTX have clinical implications. Cholestanol deposition in tissues contributes to clinical manifestations, including neurological symptoms and tendon xanthomas. Dyslipidemia and abnormal cholesterol metabolism may also contribute to the increased risk of atherosclerosis and cardiovascular complications observed in some CTX patients. [ABSTRACT FROM AUTHOR]

Background and purpose: Krabbe disease (KD), or globoid cell leukodystrophy (Online Mendelian Inheritance in Man #245200), is an autosomal recessive lysosomal storage disease caused by mutations in GALC leading to galactocerebrosidase deficiency. Age at onset can vary from early infancy (3–6 months of age) to adulthood, which has rarely been reported. Little is known about the natural history and early manifestations of adult onset KD (AOKD). Methods: Here, we report a patient with an incidental diagnosis of AOKD and discuss management options in this scenario. Results: A 32‐year‐old woman came to medical attention because of headache and had brain magnetic resonance imaging findings compatible with AOKD, two pathogenic variants in GALC, and reduced activity of galactocerebrosidase. The jury is still out about the best management of such cases, and clinicians should be aware of this diagnosis, as AOKD is a potentially treatable condition. Conclusions: AOKD is a rare and potentially treatable condition. More studies on natural history of AOKD are urgently needed to guide the best management of this disease. [ABSTRACT FROM AUTHOR]

This editorial discusses a special issue of the journal Brain Sciences that focuses on neurogenetic disorders across the lifespan, from infancy to adulthood. The issue includes papers that cover various aspects of these disorders, such as their natural history, epidemiology, diagnosis, and treatment approaches. The authors highlight the importance of studying rare presentations, expanded phenotypes, and treatment specificities for neurogenetic diseases. The editorial also mentions the underrepresentation of Latin American and Indian patients in genetic disorder studies and the need for a comprehensive understanding of these diseases to improve diagnostic procedures and identify unmet therapeutic needs. [Extracted from the article]

This article discusses a case of neuropathic tremor in a 13-year-old boy who developed the tremor after Guillain-Barré syndrome (GBS). The patient initially received treatment with propranolol, but did not respond significantly. However, when pregabalin was introduced, the tremor improved. The article suggests that pregabalin may be an effective treatment option for neuropathic tremor after GBS, while propranolol may have limited efficacy. The authors note that there are few reports on this topic and further research is needed. [Extracted from the article]

Autoimmune encephalitis is an increasingly recognized cause of encephalitis. The majority of case series report patients residing in developed countries in the northern hemisphere. The epidemiologic features of autoimmune encephalitis in Latin America are still unclear. The aim of the study was to perform a review of the clinical presentation of autoimmune encephalitis in Latin America and compare to world literature. References were identified by an in-depth literature search and selected on the basis of relevance to the topic and authors' judgment. We selected clinical studies and case reports published from 2007 to July, 2020 including patients from Latin American countries. Of the 379 patients included, the majority were cases of anti-NMDA receptor encephalitis (93.14%), followed by anti-VGKC-complex encephalitis (N = 17; 4.48%), anti-GAD encephalitis (N = 9; 2.37%), anti-AMPA receptor encephalitis (N = 1; 0.26%), anti-GABA receptor encephalitis (N = 1; 0. 26%), anti-mGluR5 encephalitis (N = 1; 0. 26%), and anti-mGluR1 encephalitis (N = 1; 0. 26%). Reported cases of Anti-NMDA encephalitis in Latin-America had a very slight female predominance, lower prevalence of associated tumors and a lower incidence of extreme delta brush on electroencephalogram. Autoimmune encephalitis is possibly underdiagnosed in underdeveloped countries. Its outcome after treatment, however, appears to be similarly favorable in Latin American patients as has been reported in developed countries based on available case reports and case series. Regional specificities in the manifestation of autoimmune encephalitis could be related to epidemiologic factors, such as the presence of different triggers and different genetic and immunologic background, that need to be studied by future research. [ABSTRACT FROM AUTHOR]

Acute encephalitis is a debilitating neurological disorder associated with brain inflammation and rapidly progressive encephalopathy. Autoimmune encephalitis (AE) is increasingly recognized as one of the most frequent causes of encephalitis, however signs of inflammation are not always present at the onset which may delay the diagnosis. We retrospectively assessed patients with AE associated with antibodies against neuronal surface diagnosed in reference centers in Northeast of Brazil between 2014 to 2017. CNS inflammatory markers were defined as altered CSF (pleocytosis >5 cells/mm3) and/or any brain parenchymal MRI signal abnormality. Thirteen patients were evaluated, anti-NMDAR was the most common antibody found (10/13, 77%), followed by anti-LGI1 (2/13, 15%), and anti-AMPAR (1/13, 7%). Median time to diagnosis was 4 months (range 2–9 months). Among these 13 patients, 6 (46.1%) had inflammatory markers and when compared to those who did not present signs of inflammation, there were no significant differences regarding the age of onset, time to diagnosis and modified Rankin scale score at the last visit. Most of the patients presented partial or complete response to immunotherapy during follow-up. Our findings suggest that the presence of inflammatory markers may not correlate with clinical presentation or prognosis in patients with AE associated with antibodies against neuronal surface. Neurologists should be aware to recognize clinical features of AE and promptly request antibody testing even without evidence of inflammation in CSF or MRI studies. [ABSTRACT FROM AUTHOR]

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Medical students are at higher risk for depression, affecting not only their lives but also patient care. This article studied a population of medical students engaged in lecture-based learning regarding the presence of depressive symptoms and its relation to morningness-eveningness. Depressive symptoms were assessed by the Beck Depressive Inventory scale (BDI>10), and diurnal preference was assessed by the Horne & Östberg Morningness/Eveningness Questionnaire (MEQ). Family history of depression and involvement in regular physical activity were also investigated. A total of 161 students, 77 (47.8%) males, aged 19 to 30 yrs (22.1±2.1) living in a city close to the equator were evaluated. Fifty-three individuals (32.9%) had depressive symptoms. Depressive individuals showed a trend to be female (p=0.07). Also, female gender showed a non-significant shift toward morningness. Fifty-eight (36.0%) subjects participated in regular physical activity. In 57 cases (35.4%), there was a history of depression in the family. Fifteen individuals (9.3%) were definitely evening type, 42 (26.1%) were moderately evening type, 44 (27.3%) were indifferent, 42 (26.1%) were moderately morning type, and 18 (11.2%) were definitely morning type. Family history of depression (OR=0.29, 95% CI=1.37-6.12) and sedentary life (OR=0.28, 95% CI=0.12-0.65) were associated with depressive symptoms. Eveningness was associated with depressive symptoms (OR=0.66, 95% CI=0.50-0.88), and this association remained significant after adjusting for the presence of familial depression and physical activity (OR=0.71, 95% CI=0.52-0.95). In conclusion, depressive symptoms are independently associated with "eveningness" in medical students. These results should be confirmed by future studies involving a larger number of subjects. [ABSTRACT FROM AUTHOR]

A 34-year-old man developed severe envenomation after being bitten by a Crotalus durissus (rattlesnake), which was treated with anticrotalic serum. Three weeks later, the patient reported paresthesia and neuropathic pain in the left hand, which had progressed to all four limbs. Electroneuromyography revealed asymmetric axonal sensorimotor multiple mononeuropathy. The patient was treated with prednisone, and six months later there was significant improvement in sensorimotor conduction. This is the first reported case of multiple mononeuropathy associated with C. durissus envenomation. Post-snake envenomation peripheral neuropathy is a rare complication requiring prompt recognition and treatment to optimize nerve function and enhance patient outcomes.

Objectives: Pathogenic variants in presenilin 1 (PSEN1) are related to early-onset Alzheimer disease (AD) and may occur as de novo variants. In comparison with sporadic forms, it can present with psychiatric manifestations, seizures, myoclonus, and focal presentation. Because PSEN1 can occur in young patients who lack a family history of neurologic disorders and because these symptoms are also frequent in autoimmune encephalitis (AE), diagnosis may be overlooked. Our aim was to demonstrate the challenge in diagnosing young patients with neurodegenerative diseases that simulate AE., Methods: We describe a case of a young patient with insidious progressive dementia, myoclonus, seizures, and aphasia, with no family history of dementia, along with signs suggestive of neuroinflammation on brain MRI and CSF examination., Results: She was initially misdiagnosed as having AE. Further investigation was performed, leading to the discovery of a novel and de novo pathogenic variant in PSEN1., Discussion: This case demonstrates the importance of considering PSEN1 in young patients with insidious progressive dementia with atypical clinical and neuroimaging features, even in patients without a family history of neurologic disorders. Not adhering to published criteria of possible and probable AE and overinterpretation of subtle inflammatory findings in CSF and MRI contribute to misdiagnosis.

Background:  Autoimmune encephalitis (AIE) is a group of inflammatory diseases characterized by the presence of antibodies against neuronal and glial antigens, leading to subacute psychiatric symptoms, memory complaints, and movement disorders. The patients are predominantly young, and delays in treatment are associated with worse prognosis., Objective:  With the support of the Brazilian Academy of Neurology (Academia Brasileira de Neurologia, ABN) and the Brazilian Society of Child Neurology (Sociedade Brasileira de Neurologia Infantil, SBNI), a consensus on the diagnosis and treatment of AIE in Brazil was developed using the Delphi method., Methods:  A total of 25 panelists, including adult and child neurologists, participated in the study., Results:  The panelists agreed that patients fulfilling criteria for possible AIE should be screened for antineuronal antibodies in the serum and cerebrospinal fluid (CSF) using the tissue-based assay (TBA) and cell-based assay (CBA) techniques. Children should also be screened for anti-myelin oligodendrocyte glucoprotein antibodies (anti-MOG). Treatment should be started within the first 4 weeks of symptoms. The first-line option is methylprednisolone plus intravenous immunoglobulin (IVIG) or plasmapheresis, the second-line includes rituximab and/or cyclophosphamide, while third-line treatment options are bortezomib and tocilizumab. Most seizures in AIE are symptomatic, and antiseizure medications may be weaned after the acute stage. In anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis, the panelists have agreed that oral immunosuppressant agents should not be used. Patients should be evaluated at the acute and postacute stages using functional and cognitive scales, such as the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), the Modified Rankin Scale (mRS), and the Clinical Assessment Scale in Autoimmune Encephalitis (CASE)., Conclusion:  The present study provides tangible evidence for the effective management of AIE patients within the Brazilian healthcare system., Competing Interests: LAD reports that she has received a grant for the Brazilian Autoimmune Encephalitis Network (Rede Brasileira de Encefalites Autoimunes), from Laboratório Fleury., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/).)