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The Israel Medical Association Journal... Jun 2013
Topics: Compartment Syndromes; Humans; Paraparesis; Posture; Rhabdomyolysis; Sleep
PubMed: 23882908
DOI: No ID Found -
American Journal of Human Genetics Apr 2023The vast majority of human genes encode multiple isoforms through alternative splicing, and the temporal and spatial regulation of those isoforms is critical for...
The vast majority of human genes encode multiple isoforms through alternative splicing, and the temporal and spatial regulation of those isoforms is critical for organismal development and function. The spliceosome, which regulates and executes splicing reactions, is primarily composed of small nuclear ribonucleoproteins (snRNPs) that consist of small nuclear RNAs (snRNAs) and protein subunits. snRNA gene transcription is initiated by the snRNA-activating protein complex (SNAPc). Here, we report ten individuals, from eight families, with bi-allelic, deleterious SNAPC4 variants. SNAPC4 encoded one of the five SNAPc subunits that is critical for DNA binding. Most affected individuals presented with delayed motor development and developmental regression after the first year of life, followed by progressive spasticity that led to gait alterations, paraparesis, and oromotor dysfunction. Most individuals had cerebral, cerebellar, or basal ganglia volume loss by brain MRI. In the available cells from affected individuals, SNAPC4 abundance was decreased compared to unaffected controls, suggesting that the bi-allelic variants affect SNAPC4 accumulation. The depletion of SNAPC4 levels in HeLa cell lines via genomic editing led to decreased snRNA expression and global dysregulation of alternative splicing. Analysis of available fibroblasts from affected individuals showed decreased snRNA expression and global dysregulation of alternative splicing compared to unaffected cells. Altogether, these data suggest that these bi-allelic SNAPC4 variants result in loss of function and underlie the neuroregression and progressive spasticity in these affected individuals.
Topics: Paraparesis, Spastic; Humans; Alternative Splicing; DNA-Binding Proteins; Transcription Factors; HeLa Cells; Protein Isoforms; RNA-Seq; Male; Female; Pedigree; Alleles; Infant; Child, Preschool; Child; Adolescent; Protein Structure, Secondary; RNA, Small Nuclear
PubMed: 36965478
DOI: 10.1016/j.ajhg.2023.03.001 -
Cureus Mar 2022Coronavirus disease 2019 (COVID-19) is primarily a disease of the respiratory system but severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may cause several...
Coronavirus disease 2019 (COVID-19) is primarily a disease of the respiratory system but severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may cause several immune-related complications including different neurological disorders, such as myelopathy with paraparesis.In this atypical case a female patient with progressive spastic paraparesis after COVID-19 infection, brisk reflexes and positive Babinski sign, reduced vibratory sensation to the thoracic level, elevated immunoglobulin levels (IgG) in cerebrospinal fluid, but negative magnetic resonance imaging (MRI) of the brain and spine, is presented. A 57-year-old woman with spastic paraparesis and inability to walk was admitted to our neurological department. About four months before hospitalization, she started feeling numbness and tingling in the feet and lumbar spine area. Gradually, numbness and tingling ascended to the thoracic spine level Th7/8, and she developed weakness mostly in her legs. In the neurological exam she had spastic paraparesis. MRI of the brain, cervical and thoracic spine did not reveal any signal abnormality. Serological testing for SARS-CoV-2 was performed and results were highly positive IgG and IgM+IgA levels. The lumbar puncture finding confirmed the suspicion of immune-related complications after SARS-CoV-2 infection (intrathecal IgG synthesis). This case draws attention to spastic paraparesis or progressive MRI-negative myelitis after SARS-CoV-2 infection, which obviously has immune-mediated pathogenesis that happen in response to the virus or its antibodies. Similarities in spastic paraparesis after human T-lymphotropic virus (HTLV-1) or human immunodeficiency virus (HIV-1) and SARS-CoV-2 infections were observed. The patient had a good response to corticosteroid therapy and had good recovery.
PubMed: 35419244
DOI: 10.7759/cureus.23054 -
Medicine Feb 2022Here, we describe a series of 7 patients who presented with acute paraparesis due to anterior communicating artery aneurysm rupture. This study aimed to assess the...
Here, we describe a series of 7 patients who presented with acute paraparesis due to anterior communicating artery aneurysm rupture. This study aimed to assess the clinical and radiological factors associated with acute paraparesis syndrome caused by subarachnoid hemorrhage (SAH).Between June 2005 and December 2012, our institution consecutively treated 210 patients with anterior communicating aneurysm rupture within 24 hours after ictus. We divided the patients into 2 groups based on the presence (n = 7) and absence (n = 203) of acute paraparesis after anterior communicating aneurysm rupture.Diffusion-weighted magnetic resonance imaging revealed high intensity in the medial aspects of the bilateral frontal lobes in 3 patients. The mean third ventricular distance at the time of admission was 9.2 mm (range, 8-12.5 mm), and the mean bicaudate distance was 33.9 mm (range, 24-39 mm). There was a significant difference in the bicaudate distance (P = .001) and third ventricle distance (P = .001) between the 2 groups. Acute hydrocephalus and global cerebral edema (GCE) were confirmed radiologically in all patients in the acute paraparesis group. The presence of acute hydrocephalus (P = .001) and GCE (P = .003) were significantly different between the groups.Acute paraparesis syndrome after SAH is transient and gradually improves if the patient does not develop severe vasospasm. The present study demonstrates that acute paraparesis after SAH is associated with acute hydrocephalus and GCE.
Topics: Aneurysm, Ruptured; Humans; Hydrocephalus; Intracranial Aneurysm; Paraparesis; Stroke; Subarachnoid Hemorrhage; Syndrome
PubMed: 35119048
DOI: 10.1097/MD.0000000000028792 -
Journal of Veterinary Diagnostic... Jul 2022Protothecosis, an infectious disease caused by the green algae and , occurs sporadically in domestic animals and humans. Diagnosis of CNS protothecosis is based on...
Protothecosis, an infectious disease caused by the green algae and , occurs sporadically in domestic animals and humans. Diagnosis of CNS protothecosis is based on neurologic signs that indicate multifocal nervous system lesions and that follow a period of chronic diarrhea and weight loss, cytologic observation of algae in fecal culture or histopathology, and detection of the agent by PCR assay of infected tissues. Here, we report a case of a paraparetic dog with CNS protothecosis that was diagnosed definitively antemortem using CSF cytology, PCR, and DNA sequencing. A 4-y-old mixed-breed dog developed progressive paraparesis that followed weight loss and diarrhea. CSF analysis revealed marked eosinophilic pleocytosis. organisms were detected by microscopic examination of the CSF, and speciated as by CSF PCR and DNA sequencing. Other possible causes of paraparesis were ruled out using computed tomography, serology, and CSF PCR. The dog's condition deteriorated despite treatment, developing forebrain and central vestibular system clinical signs, and it was euthanized at the owner's request. Postmortem examination was declined. Our findings indicate that when CNS protothecosis is suspected, antemortem diagnosis can be made using CSF analysis and a PCR assay.
Topics: Animals; Diarrhea; Dog Diseases; Dogs; Infections; Paraparesis; Plant Breeding; Prototheca; Skin Diseases, Infectious; Spinal Cord; Weight Loss
PubMed: 35459409
DOI: 10.1177/10406387221093048 -
BMC Musculoskeletal Disorders Feb 2021To explore the therapeutic effect of early surgical intervention for active thoracic spinal tuberculosis (TB) patients with paraparesis and paraplegia.
BACKGROUND
To explore the therapeutic effect of early surgical intervention for active thoracic spinal tuberculosis (TB) patients with paraparesis and paraplegia.
METHODS
Data on 118 active thoracic spinal TB patients with paraparesis and paraplegia who had undergone surgery at an early stage (within three weeks of paraparesis and paraplegia) from January 2008 to December 2014 were retrospectively analyzed. The operation duration, blood loss, perioperative complication rate, VAS score, ASIA grade and NASCIS score of neurological status rating, Erythrocyte Sedimentation Rate (ESR), C-reactive protein (CRP), kyphotic Cobb's angle, and duration of bone graft fusion were analyzed to evaluate the therapeutic effects of surgery.
RESULTS
The mean operating time was 194.2 minutes, and the mean blood loss was 871.2 ml. The perioperative complication rate was 5.9 %. The mean preoperative VAS score was 5.3, which significantly decreased to 3.2 after the operation and continued decreasing to 1.1 at follow up (P<0.05). All cases achieved an increase of at least one ASIA grade after operation. The rate of full neurological recovery for paraplegia (ASIA grade A and B) was 18.0 % and was significantly lower than the rate (100 %) for paraparesis (ASIA grade C and D) (P<0.05). On the NASCIS scale, the difference in the neurological improvement rate between paraplegia (22.2 % ± 14.1 % in sensation and 52.2 % ± 25.8 % in movement) and paraparesis (26.7 % ± 7.5 % in sensation and 59.4 % ± 7.3 % in movement) was remarkable (P<0.05). Mean preoperative ESR and CRP were 73.1 mm /h and 82.4 mg/L, respectively, which showed a significant increase after operation (P>0.05), then gradually decreased to 11.5 ± 1.8 mm/h and 2.6 ± 0.82 mg/L, respectively, at final follow up (P<0.05). The mean preoperative kyphotic Cobb's angle was 21.9º, which significantly decreased to 6.5º after operation (P<0.05) while kyphotic correction was not lost during follow up (P>0.05). The mean duration of bone graft fusion was 8.6 ± 1.3 months.
CONCLUSIONS
Early surgical intervention may be beneficial for active thoracic spinal TB patients with paraparesis and paraplegia, with surgical intervention being more beneficial for recovery from paraparesis than paraplegia.
Topics: Debridement; Humans; Lumbar Vertebrae; Paraparesis; Paraplegia; Retrospective Studies; Spinal Fusion; Thoracic Vertebrae; Treatment Outcome; Tuberculosis, Spinal
PubMed: 33612112
DOI: 10.1186/s12891-021-04078-y -
Virology Jan 2013
Review
Topics: Adolescent; Antigens, Viral, Tumor; HLA Antigens; HTLV-I Infections; Human T-lymphotropic virus 1; Humans; Immunity, Innate; Killer Cells, Natural; Leukemia, T-Cell; Lymphoma, T-Cell; Paraparesis, Tropical Spastic; Receptors, KIR; T-Lymphocytes, Cytotoxic
PubMed: 23217623
DOI: 10.1016/j.virol.2012.09.028 -
European Journal of Physical and... Aug 2018Spastic paresis is a common feature of an upper motor neuron impairment caused by stroke, brain injury, multiple sclerosis and other central nervous system (CNS)... (Review)
Review
Spastic paresis is a common feature of an upper motor neuron impairment caused by stroke, brain injury, multiple sclerosis and other central nervous system (CNS) disorders. Existing national and international guidelines for the treatment of adult spastic paresis tend to focus on the treatment of muscle overactivity rather than the comprehensive approach to care, which may require life-long management. Person-centered care is increasingly adopted by healthcare systems in a shift of focus from "disease-oriented" towards "person-centered" medicine. The challenge is to apply this principle to the complex management of spastic paresis and to include an educative process that engages care providers and patients and encourages them to participate actively in the long-term management of their own disease. To address this issue, a group of 13 international clinicians and researchers used a pragmatic top-down methodology to evaluate the evidence and to formulate and grade the strength of recommendations for applying the principles of person-centered care to the management of spastic paresis. There is a distinct lack of clinical trial evidence regarding the application of person-centered medicine to the rehabilitation setting. However, the current evidence base supports the need to ensure that treatment interventions for spastic paresis should be centered on as far as reasonable on the patient's own priorities for treatment. Goal setting, negotiation and formal recording of agreed SMART goals should be an integral part of all spasticity management programs, and goal attainment scaling should be recorded alongside other standardized measures in the evaluation of outcome. When planning interventions for spastic paresis, the team should consider the patient and their family's capacity for self-rehabilitation, as well as ways to enhance this approach. Finally, the proposed intervention and treatment goals should consider the impact of any neuropsychological, cognitive and behavioral deficits on rehabilitation. These recommendations support a person-centric focus in the management of spastic paresis.
Topics: Adult; Botulinum Toxins, Type A; Combined Modality Therapy; Consensus; Disability Evaluation; Disease Management; Exercise Therapy; Female; Humans; Male; Paraparesis, Spastic; Patient-Centered Care; Practice Guidelines as Topic; Prognosis; Risk Assessment; Severity of Illness Index; Treatment Outcome
PubMed: 29265792
DOI: 10.23736/S1973-9087.17.04808-0 -
Journal of Neurochemistry Feb 2008Pedigrees with familial Alzheimer's disease (AD) show considerable phenotypic variability. Spastic paraparesis (SP), or progressive spasticity of the lower limbs is... (Review)
Review
Pedigrees with familial Alzheimer's disease (AD) show considerable phenotypic variability. Spastic paraparesis (SP), or progressive spasticity of the lower limbs is frequently hereditary and exists either as uncomplicated (paraparesis alone) or complicated (paraparesis and other neurological features) disease subtypes. In some AD families, with presenilin-1 (PSEN1) mutations, affected individuals also have SP. These PSEN1 AD pedigrees frequently have a distinctive and variant neuropathology, namely large, non-cored plaques without neuritic dystrophy called cotton wool plaques (CWP). The PSEN1 AD mutations giving rise to CWP produce unusually high levels of the amyloid beta peptide (Abeta) ending at position 42 or 43, and the main component of CWP is amino-terminally truncated forms of amyloid beta peptide starting after the alternative beta-secretase cleavage site at position 11. This suggests a molecular basis for the formation of CWP and an association with both SP and AD. The SP phenotype in some PSEN1 AD pedigrees also appears to be associated with a delayed onset of dementia compared with affected individuals who present with dementia only, suggesting the existence of a protective factor in some individuals with SP. Variations in neuropathology and neurological symptoms in PSEN1 AD raise the prospect that modifier genes may underlie this phenotypic heterogeneity.
Topics: Alzheimer Disease; Animals; Humans; Mutation; Paraparesis, Spastic; Pedigree; Phenotype; Plaque, Amyloid; Presenilin-1
PubMed: 17995932
DOI: 10.1111/j.1471-4159.2007.05038.x -
Rheumatology International Nov 2020Spondyloenchondrodysplasia (SPENCD) is a rare skeletal dysplasia characterized with platyspondyly and metaphyseal lesions of the long bones mimicking enchondromatosis,... (Review)
Review
Spondyloenchondrodysplasia (SPENCD) is a rare skeletal dysplasia characterized with platyspondyly and metaphyseal lesions of the long bones mimicking enchondromatosis, resulting in short stature. SPENCD often coexists with neurologic disorders and immune dysregulation. Spasticity, developmental delay and intracranial calcification are main neurologic abnormalities. Large spectrum of immunologic abnormalities may be seen in SPENCD, including immune deficiencies and autoimmune disorders with autoimmune thrombocytopenia and systemic lupus erythematosus as the most common phenotypes. SPENCD is caused by loss of tartrate-resistant acid phosphatase (TRAP) activity, due to homozygous mutations in ACP5, playing a role in non-nucleic acid-related stimulation/regulation of the type I interferon pathway. We present two siblings, 13-year-old girl and 25-year-old boy with SPENCD, from consanguineous parents. Both patients had short stature, platyspondyly, metaphyseal changes, spastic paraparesis, mild intellectual disability, and juvenile-onset SLE. The age at disease-onset was 2 years for girl and 19 years for boy. Both had skin and mucosa involvement. The age at diagnosis of SLE was 4 years for girl, and 19 years for boy. The clinical diagnosis of SPENCD was confirmed by sequencing of ACP5 gene, which revealed a homozygous c.155A > C (p.K52T), a variant reported before as pathogenic. Juvenile-onset SLE accounts for about 15-20% of all SLE cases. But, the onset of SLE before 5-years of age and also monogenic SLE are rare. Our case report and the literature review show the importance of multisystemic evaluation in the diagnosis of SPENCD and to remind the necessity of investigating the monogenic etiology in early-onset and familial SLE cases.
Topics: Adolescent; Adult; Age of Onset; Antirheumatic Agents; Autoimmune Diseases; Brain Diseases; Calcinosis; Female; Humans; Immunologic Deficiency Syndromes; Intellectual Disability; Lupus Erythematosus, Systemic; Male; Osteochondrodysplasias; Paraparesis, Spastic; Siblings; Tartrate-Resistant Acid Phosphatase
PubMed: 32691099
DOI: 10.1007/s00296-020-04653-x