-
Frontiers in Neurology 2023Sleep represents a major frontier both in clinical myology and as a new possibility for delivering treatment to neuromuscular patients since various neuromuscular cases... (Review)
Review
Sleep represents a major frontier both in clinical myology and as a new possibility for delivering treatment to neuromuscular patients since various neuromuscular cases present a variable degree of disordered sleep and such conditions should be diagnosed and prevented, i.e., sleep apnea and hypoxemia. These sleep disorders are present in dystrophinopathies and in various types of limb-girdle muscular dystrophies (LGMD). Excessive daytime sleepiness (EDS) is found in patients affected by spastic paraparesis or cerebellar ataxia but is rather common in both myotonic dystrophy type 1 and 2, and the correction of sleep disorders is therefore important to improve their daily quality of life (QoL) and consequent daily functioning. Other types of sleep dysfunction such as insomnia, a reduction in rapid eye movement (REM) sleep, loss of normal REM, or sleep-disordered breathing are found in other disorders including myasthenia, ataxias, spastic paraparesis, Charcot-Marie-Tooth disease, and neurogenic disorders, including polyneuropathies, and need appropriate treatment. Research done on this topic aims to incorporate a variety of nuances in metabolic disorders such as those in late-onset Pompe disease and are such as those in late-onset Pompe disease who are susceptible to enzyme replacement therapy (ERT). The overarching goal is to explore both the diagnosis and methodology of sleep-related problems in both genetic and acquired neuromuscular disorders. We also review the type of available treatment opportunities utilized to improve neuromuscular patients' QoL.
PubMed: 37456652
DOI: 10.3389/fneur.2023.1195302 -
Bioactive Materials Mar 2024Spinal cord injury (SCI) causes severe axon damage, usually leading to permanent paraparesis, which still lacks effective regenerative therapy. Recent studies have...
Spinal cord injury (SCI) causes severe axon damage, usually leading to permanent paraparesis, which still lacks effective regenerative therapy. Recent studies have suggested that exosomes derived from neural stem cells (NSCs) may hold promise as attractive candidates for SCI treatment. Epidermal Growth Factor Receptor positive NSC (EGFRNSC) is a subpopulation of endogenous NSCs, showing strong regenerative capability in central nervous system disease. In the current study, we isolated exosomes from the EGFRNSCs (EGFRNSCs-Exos) and discovered that local delivery of EGFRNSCs-Exos can effectively promote neurite regrowth in the injury site of spinal cord-injured mice and improve their neurological function recovery. Using the miRNA-seq, we firstly characterized the microRNAs (miRNAs) cargo of EGFRNSCs-Exos and identified miR-34a-5p which was highly enriched in EGFRNSCs derived exosomes. We further interpreted that exosomal miR-34a-5p could be transferred to neurons and inhibit the HDAC6 expression by directly binding to its mRNA, contributing to microtubule stabilization and autophagy induction for aiding SCI repair. Overall, our research demonstrated a novel therapeutic approach to improving neurological functional recovery by using exosomes secreted from a subpopulation of endogenous NSCs and providing a precise cell-free treatment strategy for SCI repair.
PubMed: 38059122
DOI: 10.1016/j.bioactmat.2023.11.013 -
Acta Neurologica Taiwanica Jun 2023A 20-month-old female, not immunized with Bacillus Calmette-Guérin (BCG) vaccine, was admitted due to a four-day history of fever and cough. In the past three months,...
A 20-month-old female, not immunized with Bacillus Calmette-Guérin (BCG) vaccine, was admitted due to a four-day history of fever and cough. In the past three months, she presented respiratory infections, weight loss and enlarged cervical lymph nodes. On day two of admission, she displayed drowsiness and positive Romberg's sign; cerebrospinal fluid (CSF) workout revealed 107/ul cells, low glucose and high protein levels. Ceftriaxone and acyclovir were initiated, and she was transferred to our tertiary hospital. Brain magnetic resonance imaging showed punctiform focal areas of restricted diffusion in left capsular lenticular region suggestive of vasculitis secondary to infection. Tuberculin skin test and interferon-gamma release assay were positive. She started tuberculostatic therapy, but two days later she presented tonic-clonic seizures and impaired consciousness. Cerebral computed tomography (CT) revealed tetrahydrocephalus (Figure 1), needing external ventricular derivation. She had a slow clinical improvement, requiring several neurosurgical interventions and developing a syndrome of inappropriate antidiuretic secretion alternating with cerebral salt wasting. Positive results for Mycobacterium tuberculosis were obtained by CSF culture and by polymerase chain reaction in CSF, bronchoalveolar lavage and gastric aspirate specimens. Repeated brain CT showed a large-vessel vasculitis with basal meningeal enhancement, typical of central nervous system (CNS) tuberculosis (Figure 2). She completed one month of corticosteroids and maintained antituberculosis treatment. At two years of age, she has spastic paraparesis and no language skills. Portugal had 1836 cases of tuberculosis (17.8 per 100000) in 2016 and was considered a low-incidence country; consequently, BCG vaccination is not universal (1). We present a severe case of CNS tuberculosis with intracranial hypertension, vasculitis and hyponatremia, associated with poorer outcomes (2). A high index of suspicion allowed prompt start of antituberculosis treatment. Diagnosis was corroborated by microbiological positivity and a typical triad in neuroimaging (hydrocephalus, vasculitis and basal meningeal enhancement) (3), which we wish to emphasize.
Topics: Humans; Female; Infant; BCG Vaccine; Tuberculosis, Central Nervous System; Tuberculosis; Neuroimaging; Antitubercular Agents; Vasculitis; Tuberculosis, Meningeal
PubMed: 37198514
DOI: No ID Found -
Arquivos de Neuro-psiquiatria Nov 2023Hereditary or familial spastic paraplegias (SPG) comprise a group of genetically and phenotypically heterogeneous diseases characterized by progressive degeneration... (Review)
Review
BACKGROUND
Hereditary or familial spastic paraplegias (SPG) comprise a group of genetically and phenotypically heterogeneous diseases characterized by progressive degeneration of the corticospinal tracts. The complicated forms evolve with other various neurological signs and symptoms, including movement disorders and ataxia.
OBJECTIVE
To summarize the clinical descriptions of SPG that manifest with movement disorders or ataxias to assist the clinician in the task of diagnosing these diseases.
METHODS
We conducted a narrative review of the literature, including case reports, case series, review articles and observational studies published in English until December 2022.
RESULTS
Juvenile or early-onset parkinsonism with variable levodopa-responsiveness have been reported, mainly in SPG7 and SPG11. Dystonia can be observed in patients with SPG7, SPG11, SPG22, SPG26, SPG35, SPG48, SPG49, SPG58, SPG64 and SPG76. Tremor is not a frequent finding in patients with SPG, but it is described in different types of SPG, including SPG7, SPG9, SPG11, SPG15, and SPG76. Myoclonus is rarely described in SPG, affecting patients with SPG4, SPG7, SPG35, SPG48, and SPOAN (spastic paraplegia, optic atrophy, and neuropathy). SPG4, SPG6, SPG10, SPG27, SPG30 and SPG31 may rarely present with ataxia with cerebellar atrophy. And autosomal recessive SPG such as SPG7 and SPG11 can also present with ataxia.
CONCLUSION
Patients with SPG may present with different forms of movement disorders such as parkinsonism, dystonia, tremor, myoclonus and ataxia. The specific movement disorder in the clinical manifestation of a patient with SPG may be a clinical clue for the diagnosis.
Topics: Humans; Spastic Paraplegia, Hereditary; Mutation; Tremor; Dystonia; Movement Disorders; Ataxia; Parkinsonian Disorders; Proteins
PubMed: 38035585
DOI: 10.1055/s-0043-1777005 -
Brain : a Journal of Neurology Aug 2023ATP1A3 encodes the α3 subunit of the sodium-potassium ATPase, one of two isoforms responsible for powering electrochemical gradients in neurons. Heterozygous pathogenic...
ATP1A3 encodes the α3 subunit of the sodium-potassium ATPase, one of two isoforms responsible for powering electrochemical gradients in neurons. Heterozygous pathogenic ATP1A3 variants produce several distinct neurological syndromes, yet the molecular basis for phenotypic variability is unclear. We report a novel recurrent variant, ATP1A3(NM_152296.5):c.2324C>T; p.(Pro775Leu), in nine individuals associated with the primary clinical features of progressive or non-progressive spasticity and developmental delay/intellectual disability. No patients fulfil diagnostic criteria for ATP1A3-associated syndromes, including alternating hemiplegia of childhood, rapid-onset dystonia-parkinsonism or cerebellar ataxia-areflexia-pes cavus-optic atrophy-sensorineural hearing loss (CAPOS), and none were suspected of having an ATP1A3-related disorder. Uniquely among known ATP1A3 variants, P775L causes leakage of sodium ions and protons into the cell, associated with impaired sodium binding/occlusion kinetics favouring states with fewer bound ions. These phenotypic and electrophysiologic studies demonstrate that ATP1A3:c.2324C>T; p.(Pro775Leu) results in mild ATP1A3-related phenotypes resembling complex hereditary spastic paraplegia or idiopathic spastic cerebral palsy. Cation leak provides a molecular explanation for this genotype-phenotype correlation, adding another mechanism to further explain phenotypic variability and highlighting the importance of biophysical properties beyond ion transport rate in ion transport diseases.
Topics: Humans; Mutation; Syndrome; Intellectual Disability; Cerebellar Ataxia; Phenotype; Muscle Spasticity; Cations; Sodium-Potassium-Exchanging ATPase
PubMed: 37043503
DOI: 10.1093/brain/awad124 -
Frontiers in Neurology 2023Hereditary spastic paraplegias (HSPs) are a group of inheritance diseases resulting in gait abnormalities, which may be detected using instrumented gait analysis. The...
BACKGROUND
Hereditary spastic paraplegias (HSPs) are a group of inheritance diseases resulting in gait abnormalities, which may be detected using instrumented gait analysis. The aim of this systematic review was 2-fold: to identify specific gait analysis patterns and interventions improving gait in HSP subjects.
METHODS
A systematic review was conducted in PubMed, Cochrane Library, REHABDATA, and PEDro databases, in accordance with reporting guidelines of PRISMA statement and Cochrane's recommendation. The review protocol was recorded on the PROSPERO register. Patients with pure and complicated HSP of any age were included. All types of studies were included. Risk of bias, quality assessment, and meta-analysis were performed.
RESULTS
Forty-two studies were included: 19 were related to gait analysis patterns, and 24 were intervention studies. The latter ones were limited to adults. HSP gait patterns were similar to cerebral palsy in younger subjects and stroke in adults. Knee hyperextension, reduced range of motion at knee, ankle, and hip, reduced foot lift, and increased rapid trunk and arm movements were reported. Botulinum injections reduced spasticity but uncovered weakness and improved gait velocity at follow-up. Weak evidence supported intrathecal baclofen, active intensive physical therapy (i.e., robot-assisted gait training, functional exercises, and hydrotherapy), and functional electrical stimulation. Some improvements but adverse events were reported after transcranial magnetic stimulation, transcutaneous spinal direct current stimulation, and spinal cord stimulation implant.
CONCLUSION
Knee hyperextension, non-sagittal pelvic movements, and reduced ROM at the knee, ankle, and hip represent the most peculiar patterns in HSP, compared to diplegic cerebral palsy and stroke. Botulinum improved comfortable gait velocity after 2 months. Nonetheless, interventions reducing spasticity might result in ineffective functional outcomes unveiling weakness. Intensive active physical therapy and FES might improve gait velocity in the very short term.
PubMed: 37799279
DOI: 10.3389/fneur.2023.1256392 -
Virulence Dec 2023Human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropic spastic paraparesis (HAM/TSP) is an insidiously progressive spinal cord disease for which...
Human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropic spastic paraparesis (HAM/TSP) is an insidiously progressive spinal cord disease for which there is no effective treatment. There is great interest in developing potential biomarkers to predict the pathogenesis of HAM/TSP disease. In this study, Illumina Massive Parallel Sequencing (MPS) technology was used to investigate the cellular global noncoding RNAome expression profile in HAM/TSP patients ( = 10), asymptomatic HTLV-1-infected carriers (ASP, = 8), and a second group of healthy controls ( = 5). Various bioinformatics tools were used to align, annotate, and profile the sRNA-MPS reads. Among the 402 sRNAs detected, 251 were known and 50 were potentially novel sRNAs in the HAM and ASP groups compared with the HC group. Sixty-eight known sRNAs were significantly different between the ASP and HAM groups. Eighty-eight mature miRNAs were downregulated in subjects from HAM compared with ASP. Three of these miRs (hsa-miR-185-5p, 32-5p, and 192-5p) have the potential to be used as biomarkers for predicting the pathogenesis of HAM/TSP. The seven most deregulated miRs target genes have been associated with a variety of biological processes and molecular functions. The reactome pathways relevant to our findings provide a rich source of data and offer the opportunity to better understand sRNA regulation and function in HTLV-1 pathophysiology. To the best of our knowledge, this study is the first to demonstrate evaluates sRNAs in HTLV-1 patients with HAM/TSP.
Topics: Humans; Prognosis; Paraparesis, Tropical Spastic; Human T-lymphotropic virus 1; MicroRNAs; Biomarkers
PubMed: 37394816
DOI: 10.1080/21505594.2023.2230015 -
European Journal of Case Reports in... 2024Hyperargininemia is a rare inherited metabolic disorder of the urea cycle with an autosomal recessive transmission. It occurs due to a deficiency of the enzyme arginase...
BACKGROUND
Hyperargininemia is a rare inherited metabolic disorder of the urea cycle with an autosomal recessive transmission. It occurs due to a deficiency of the enzyme arginase I and causes progressive neurological damage. Very few cases are diagnosed in adulthood, with the majority being diagnosed before the age of 4. Currently, this condition is diagnosed by a mass spectrometry technique in neonatal screening, which has been implemented in Portugal since 2007; births before that were not screened for this entity.
CASE DESCRIPTION
We present a case of a 23-year-old woman referred to the internal medicine and neurology departments with a history of two hospital admissions for rhabdomyolysis at the age of 18, consanguineous parents, learning difficulties and multiple falls since the age of 8. In addition, the patient also had behavioural changes so she had psychological counselling at school, but lacked family support. Neurological examination showed mild proximal paraparesis, and spastic and paraparetic gait. The aetiological study revealed a pathological variant in homozygosity and increased blood levels of arginine. Therefore, the diagnosis of hyperargininemia was confirmed.
CONCLUSIONS
Compared to other urea cycle disorders, hyperargininemia is the rarest one. It is important to recognise the characteristic clinical features and diagnose it early because a favourable outcome can be achieved with appropriate treatment. This case shows a delayed diagnosis of hyperargininemia and highlights the importance of the internist's role in diagnosing rare diseases.
LEARNING POINTS
Hyperargininemia is a rare hereditary metabolic disease of the urea cycle and the rarest of the disorders affecting this cycle.The diagnosis is almost always made within the first four years of life and very few are diagnosed in adulthood.Early diagnosis is essential to reduce the progression of neurological damage, through appropriate treatment.
PubMed: 38584907
DOI: 10.12890/2024_004379 -
Frontiers in Immunology 2023Extracellular vesicles and particles (EVPs) are released from virtually all cell types, and may package many inflammatory factors and, in the case of infection, viral...
BACKGROUND AND OBJECTIVES
Extracellular vesicles and particles (EVPs) are released from virtually all cell types, and may package many inflammatory factors and, in the case of infection, viral components. As such, EVPs can play not only a direct role in the development and progression of disease but can also be used as biomarkers. Here, we characterized immune signatures of EVPs from the cerebrospinal fluid (CSF) of individuals with HTLV-1-associated myelopathy (HAM), other chronic neurologic diseases, and healthy volunteers (HVs) to determine potential indicators of viral involvement and mechanisms of disease.
METHODS
We analyzed the EVPs from the CSF of HVs, individuals with HAM, HTLV-1-infected asymptomatic carriers (ACs), and from patients with a variety of chronic neurologic diseases of both known viral and non-viral etiologies to investigate the surface repertoires of CSF EVPs during disease.
RESULTS
Significant increases in CD8+ and CD2+ EVPs were found in HAM patient CSF samples compared to other clinical groups ( = 0.0002 and = 0.0003 compared to HVs, respectively, and = 0.001 and = 0.0228 compared to MS, respectively), consistent with the immunopathologically-mediated disease associated with CD8+ T-cells in the central nervous system (CNS) of HAM patients. Furthermore, CD8+ ( < 0.0001), CD2+ ( < 0.0001), CD44+ ( = 0.0176), and CD40+ ( = 0.0413) EVP signals were significantly increased in the CSF from individuals with viral infections compared to those without.
DISCUSSION
These data suggest that CD8+ and CD2+ CSF EVPs may be important as: 1) potential biomarkers and indicators of disease pathways for viral-mediated neurological diseases, particularly HAM, and 2) as possible meditators of the disease process in infected individuals.
Topics: Humans; Paraparesis, Tropical Spastic; Central Nervous System; Extracellular Vesicles; Nervous System Diseases; CD40 Antigens; Chronic Disease
PubMed: 37622115
DOI: 10.3389/fimmu.2023.1235791