Differential Diagnosis or Etiology: A Case Report on Amyotrophic Lateral Sclerosis-like Neuropathy Associated with HIV Infection.

BACKGROUND: Retroviruses are described as a risk factor for chronic neuropathy. However, it is still unknown if they can work as amyotrophic lateral sclerosis triggers. Over the years, some cases of this association have been described with heterogenous disclosures. CASE REPRESENTATION: This study aimed to report a case of HIV and ALS-like neuropathy and briefly discuss peculiarities of clinical aspects, such as physiopathology and treatment options. The patient underwent neurological examination associated with blood tests, electromyography, analysis of cerebrospinal fluid, and imaging studies. DISCUSSION: A non-systematic review was performed in major databases regarding the topic. The case presented mixed upper and lower motor neuron signs and was framed as a probable case of ALS following the present criteria. CONCLUSION: After a short follow-up and viral load cleansing, neurological stabilization was achieved.

Brazilian registry of patients with porphyria: REBRAPPO study.

BACKGROUND: Porphyrias are a rare group of disease due to inherited defects of heme synthesis with important systemic manifestations and great burden of disease for patients and families due to the exceptional course of disease with disabling chronic symptoms interposed by life-threatening acute attacks. Unfortunately, the porphyrias are usually underrecognized reflecting a lack of medical and disease awareness as well as few studies about natural history in large cohorts of patients. The main aim of this article is present consistent data about natural history and burden of disease in a large Brazilian cohort. METHODS: We conducted a national cross-sectional registry with retrospective clinical data of Brazilian patients with porphyria collected with Brazilian patients Association with Porphyria in collaboration with a tertiary care center for rare diseases. RESULTS: A cohort of 172 patients was analyzed in which 148 (86%) patients had the diagnosis of acute hepatic porphyria [AHP] that needed a mean of 62.04 medical visits and 9.6 years to achieve a definitive diagnosis. About AHP cohort, the most common first clinical manifestation were abdominal pain in 77 (52%) patients and acute muscle weakness in 23 (15.5%) with 73 (49.3%) patients presenting only one attack during disease course and 37 (25%) exhibiting 4 or more attacks in the last year. Of note, 105 patients with AHP reported chronic manifestations and the scores for quality of life are lower when compared with general healthy population. CONCLUSIONS: Brazilian patients with AHP had a higher prevalence of chronic disabling manifestations and a poor quality of life like other cohorts and a higher proportion of patients with recurrent attacks than previously reported.

A multinational study of acute and long-term outcomes of Type 1 galactosemia patients who carry the S135L (c.404C > T) variant of GALT.

Patients with galactosemia who carry the S135L (c.404C > T) variant of galactose-1-P uridylyltransferase (GALT), documented to encode low-level residual GALT activity, have been under-represented in most prior studies of outcomes in Type 1 galactosemia. What is known about the acute and long-term outcomes of these patients, therefore, is based on very limited data. Here, we present a study comparing acute and long-term outcomes of 12 patients homozygous for S135L, 25 patients compound heterozygous for S135L, and 105 patients homozygous for two GALT-null (G) alleles. This is the largest cohort of S135L patients characterized to date. Acute disease following milk exposure in the newborn period was common among patients in all 3 comparison groups in our study, as were long-term complications in the domains of speech, cognition, and motor outcomes. In contrast, while at least 80% of both GALT-null and S135L compound heterozygous girls and women showed evidence of an adverse ovarian outcome, prevalence was only 25% among S135L homozygotes. Further, all young women in this study with even one copy of S135L achieved spontaneous menarche; this is true for only about 33% of women with classic galactosemia. Overall, we observed that while most long-term outcomes trended milder among groups of patients with even one copy of S135L, many individual patients, either homozygous or compound heterozygous for S135L, nonetheless experienced long-term outcomes that were not mild. This was true despite detection by newborn screening and both early and life-long dietary restriction of galactose. This information should empower more evidence-based counseling for galactosemia patients with S135L.

MR imaging of inherited myopathies: a review and proposal of imaging algorithms.

PURPOSE OF REVIEW: The aims of this review are to discuss the imaging modalities used to assess muscle changes in myopathies, to provide an overview of the inherited myopathies focusing on their patterns of muscle involvement in magnetic resonance imaging (MR), and to propose up-to-date imaging-based diagnostic algorithms that can help in the diagnostic workup. CONCLUSION: Familiarization with the most common and specific patterns of muscular involvement in inherited myopathies is very important for radiologists and neurologists, as imaging plays a significant role in diagnosis and follow-up of these patients. KEY POINTS: • Imaging is an increasingly important tool for diagnosis and follow-up in the setting of inherited myopathies. • Knowledge of the most common imaging patterns of muscle involvement in inherited myopathies is valuable for both radiologists and neurologists. • In this review, we present imaging-based algorithms that can help in the diagnostic workup of myopathies.

Should we investigate mitochondrial disorders in progressive adult-onset undetermined ataxias?

BACKGROUND: Despite the broad development of next-generation sequencing approaches recently, such as whole-exome sequencing, diagnostic workup of adult-onset progressive cerebellar ataxias without remarkable family history and with negative genetic panel testing for SCAs remains a complex and expensive clinical challenge. CASE PRESENTATION: In this article, we report a Brazilian man with adult-onset slowly progressive pure cerebellar ataxia, which developed neuropathy and hearing loss after fifteen years of ataxia onset, in which a primary mitochondrial DNA defect (MERRF syndrome - myoclonus epilepsy with ragged-red fibers) was confirmed through muscle biopsy evaluation and whole-exome sequencing. CONCLUSIONS: Mitochondrial disorders are a clinically and genetically complex and heterogenous group of metabolic diseases, resulting from pathogenic variants in the mitochondrial DNA or nuclear DNA. In our case, a correlation with histopathological changes identified on muscle biopsy helped to clarify the definitive diagnosis. Moreover, in neurodegenerative and neurogenetic disorders, some symptoms may be evinced later during disease course. We suggest that late-onset and adult pure undetermined ataxias should be considered and investigated for mitochondrial disorders, particularly MERRF syndrome and other primary mitochondrial DNA defects, together with other more commonly known nuclear genes.

Hereditary Spastic Paraplegia: Clinical and Genetic Hallmarks.

Hereditary spastic paraplegia comprises a wide and heterogeneous group of inherited neurodegenerative and neurodevelopmental disorders resulting from primary retrograde dysfunction of the long descending fibers of the corticospinal tract. Although spastic paraparesis and urinary dysfunction represent the most common clinical presentation, a complex group of different neurological and systemic compromise has been recognized recently and a growing number of new genetic subtypes were described in the last decade. Clinical characterization of individual and familial history represents the main step during diagnostic workup; however, frequently, few and unspecific data allows a low rate of definite diagnosis based solely in clinical and neuroimaging basis. Likewise, a wide group of neurological acquired and inherited disorders should be included in the differential diagnosis and properly excluded after a complete laboratorial, neuroimaging, and genetic evaluation. The aim of this review article is to provide an extensive overview regarding the main clinical and genetic features of the classical and recently described subtypes of hereditary spastic paraplegia (HSP).

Non-motor and Extracerebellar Features in Spinocerebellar Ataxia Type 2.

Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant degenerative disease. Pathological studies have demonstrated not only cerebellar and brainstem atrophy, but substantia nigra, motoneurons, basal ganglia, thalamus, and peripheral nerves involvement. These findings may explain non-motor and extra-cerebellar features in SCA2. We accessed the non-motor symptoms and extra-cerebellar signs in SCA2 patients in order to provide a better understanding on pathophysiological mechanisms and natural history of brain degeneration in the disease. Thirty-three SCA2 patients were evaluated and compared with 26 healthy subjects. We investigated the following variables: sleep disorders, cognitive deficit, olfactory impairment, urinary dysfunction, psychiatric symptoms, cramps, pain, movement disorders, and weight loss. SCA2 had a high frequency of REM sleep behavior disorder (48.48 %, N = 16) as well as excessive daytime sleepiness (42.42 %, N = 14). Chorea was present in 15.15 % (N = 5), dystonia in 27.27 % (N = 9), and parkinsonism in 27.27 % (N = 9). Slow saccadic pursuit was present in 87.87 % (N = 29) and ophtalmoparesis in 78.78 % (N = 26) of patients. Regarding sleep disorders, 18.18 % (N = 6) of patients had restless leg syndrome. Dysphagia was present in 39.39 % (N = 13), weight loss 24.24 % (N = 8), and urinary dysfunction 27.27 % (N = 9). Cramps was present in only 6 % of patients (N = 2). This study highlighted the high frequency of non-motor symptoms and extra-cerebellar signs in SCA2. Our findings demonstrate the widespread of nervous system involvement in SCA2 patients and contribute to better understand the natural history of brain degeneration in this genetic condition.

Normal muscle structure, growth, development, and regeneration.

Knowledge about biochemical, structural and physiological aspects, and properties regarding the skeletal muscle has been widely obtained in the last decades. Muscle disorders, mainly represented in neuromuscular clinical practice by acquired and hereditary myopathies, are well-recognized and frequently diagnosed in practice. Most clinical complaints and biochemical characterizations of each myopathy depends on the appropriate knowledge and interpretation of pathological findings and their comparison with normal muscle findings. Great improvement has been obtained in the last decades mainly involving the mechanisms of normal muscle architecture and physiological function in the healthy individuals. Genetic mechanisms have also been widely studied. We provide an extensive literature review involving current knowledge regarding muscle cell structure and function and embryological and regenerative processes linked to muscle lesion. An updated comprehensive description involving the main nuclear genomic regulatory mechanisms of muscle regeneration and embryogenesis is provided in this review.