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Case Reports in Genetics 2023Genetic variants in are the most common cause of hereditary spastic paraplegia (HSP), entitled spastic paraplegia type 4 (SPG4). Inheritance is autosomal dominant, and...
Genetic variants in are the most common cause of hereditary spastic paraplegia (HSP), entitled spastic paraplegia type 4 (SPG4). Inheritance is autosomal dominant, and age of onset can vary from childhood to adulthood. Pathogenic variants are often observed in isolated cases, likely due to reduced penetrance and clinical variability. We report an isolated case of SPG4 associated with a novel likely pathogenic variant in . A 38-year-old woman presented with an eight-year history of progressive difficulty walking. Neurological examination revealed spastic paraparesis in the absence of upper motor neuron dysfunction, sensory deficits, or intellectual disability. Magnetic resonance imaging (MRI) of the brain and spinal cord was normal. No family members had similar complaints. Genetic analysis revealed a novel heterozygous sequence variant in , c.1751A > G p.(Asp584Gly) (NM_014946.4). The affected amino acid is highly conserved among orthologue and paralogue species. Four other nucleotide substitutions predicted to affect the same amino acid, a "hot spot", have been reported previously in adult-onset HSP. This report describes a novel variant in a female with HSP without a known family history of the disorder.
PubMed: 38186854
DOI: 10.1155/2023/4553365 -
Surgical Neurology International 2024Congenital, acquired, and iatrogenic spinal epidermoid cysts (EC) are very rare.
BACKGROUND
Congenital, acquired, and iatrogenic spinal epidermoid cysts (EC) are very rare.
METHODS
A 62-year-old female patient presented with a 5-month history of progressive paraparesis leading to paraplegia secondary to a posterior compressive intradural extramedullary lesion at the T7 level. The patient underwent a laminectomy/durotomy for gross total tumor excision.
RESULTS
Histopathology confirmed the lesion was an epidermoid cyst. Although her spasticity improved within 5 weeks, she only regained partial lower extremity motion (i.e., 3/5 motor function).
CONCLUSION
Patients presenting with the acute/subacute onset of paraparesis secondary to spinal EC should undergo timely gross total cyst resections to optimize neurological outcomes.
PubMed: 38840622
DOI: 10.25259/SNI_280_2024 -
Clinical Case Reports Jul 2023TBM has a very high rate of adverse sequelae if not treated immediately. Diagnosing can be challenging due to overlapping symptoms with other disease processes, and...
KEY CLINICAL MESSAGE
TBM has a very high rate of adverse sequelae if not treated immediately. Diagnosing can be challenging due to overlapping symptoms with other disease processes, and diagnostic tests are often inconclusive.
ABSTRACT
A 20-year-old man experienced progressive paraplegia and urinary retention. After extensive laboratory and imaging evaluation for tuberculous meningitis and alternative diagnoses, spinal MRI showed features suggestive of arachnoiditis. He was treated empirically with anti-tuberculosis drugs and corticosteroids. This led to significant improvement and eventual recovery.
PubMed: 37476602
DOI: 10.1002/ccr3.7698 -
Infectious Agents and Cancer May 2024Human T-cell Lymphotropic virus type 1 (HTLV-1) belongs to retroviridae which is connected to two major diseases, including HTLV-1-associated myelopathy/tropical spastic...
INTRODUCTION
Human T-cell Lymphotropic virus type 1 (HTLV-1) belongs to retroviridae which is connected to two major diseases, including HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and Adult T-cell leukemia/lymphoma (ATLL). This study aims to investigate the mRNA expressions of key proteins correlated to T-cell activation in asymptomatic carriers (ACs) HTLV-1 infected patients, shedding light on early molecular events and T-cell activation following HTLV-1 infection.
MATERIAL AND METHODS
The study involved 40 participants, including 20 ACs and 20 healthy subjects. Blood samples were collected, ELISA assessment for screening and confirmation with PCR for Trans-activating transcriptional regulatory protein (Tax) and HTLV-1 basic leucine zipper factor (HBZ) of the HTLV-1 were done. mRNA expressions of C-terminal Src kinase (CSK), Glycogen Synthase Kinase-3 Beta (GSK3β), Mitogen-Activated Protein Kinase 14 (MAP3K14 or NIK), Phospholipase C Gamma-1 (PLCG1), Protein Tyrosine Phosphatase non-Receptor Type 6 (PTPN6) and Mitogen-Activated Protein Kinase Kinase Kinase-7 (SLP-76) and Mitogen-Activated Protein Kinase14 (MAP3K7 or TAK1) were assayed using RT-qPCR. Statistical analyses were performed using PRISM and SPSS software.
RESULTS
While there were no significant upregulation in CSK and PTPN6 in ACs compared to healthy individuals, expression levels of GSK3β, MAP3K14, PLCG1, SLP-76, and TAK1 were significantly higher in ACs compared to healthy subjects which directly contributes to T-cell activation in the HTLV-1 ACs.
CONCLUSION
HTLV-1 infection induces differential mRNA expressions in key proteins associated with T-cell activation. mRNAs related to T-cell activation showed significant upregulation compared to PTPN6 and CSK which contributed to T-cell regulation. Understanding these early molecular events in ACs may provide potential markers for disease progression and identify therapeutic targets for controlling viral replication and mitigating associated diseases. The study contributes novel insights to the limited literature on T-cell activation and HTLV-1 pathogenesis.
PubMed: 38734673
DOI: 10.1186/s13027-024-00584-5 -
Isolated Tuberculous Transverse Myelitis Without Meningitis Among Patients With AIDS: A Case Report.Cureus Dec 2023Acute transverse myelitis is an inflammatory disorder of the spinal cord, characterized by acute or subacute onset of paraparesis, bilateral sensory deficit, and...
Acute transverse myelitis is an inflammatory disorder of the spinal cord, characterized by acute or subacute onset of paraparesis, bilateral sensory deficit, and impaired urinary bladder and sphincter tone function. , a very rare cause of transverse myelitis, especially tuberculous myelitis without meningitis, is extremely rare. The main etiologic mechanism consists of an abnormal activation of the immune system against the spinal cord as well as the direct invasion by the bacillus. We present a 30-year-old Thai woman with AIDS, presenting with paraplegia for two days. Her MRI of the whole spine showed nodular enhancing intramedullary lesions involving the spinal cord at the T11-T12 level, and intramedullary enhancing lesion along the T12 spinal cord to the conus medullaris. Cerebrospinal fluid (CSF) examination revealed only a few white blood cells without hypoglycorrhachia or elevated CSF protein. CSF polymerase chain reaction (PCR) and culture for produced negative results. Other investigations did not demonstrate other organ involvement. Spinal cord biopsy at T12 was performed and exhibited diffuse epithelioid histiocytic proliferation admixed with small lymphocytes and plasma cells with numerous acid-fast bacilli (AFB)-positive bacilli organisms. PCR for was also detected in spinal cord tissue. Thus, acute transverse myelitis caused by isolated tuberculous myelitis without meningeal involvement was diagnosed. She had marked clinical improvement and neurologic recovery after treatment with anti-tuberculosis and intravenous steroid pulses. Isolated spinal tuberculous myelitis without meningitis is exceptionally uncommon and should be carefully considered, particularly in severely immunocompromised individuals residing in regions with a high tuberculosis burden.
PubMed: 38229805
DOI: 10.7759/cureus.50650 -
American Journal of Human Genetics Dec 2023Hereditary spastic parapareses (HSPs) are clinically heterogeneous motor neuron diseases with variable age of onset and severity. Although variants in dozens of genes...
Hereditary spastic parapareses (HSPs) are clinically heterogeneous motor neuron diseases with variable age of onset and severity. Although variants in dozens of genes are implicated in HSPs, much of the genetic basis for pediatric-onset HSP remains unexplained. Here, we re-analyzed clinical exome-sequencing data from siblings with HSP of unknown genetic etiology and identified an inherited nonsense mutation (c.523C>T [p.Arg175Ter]) in the highly conserved RAB1A. The mutation is predicted to produce a truncated protein with an intact RAB GTPase domain but without two C-terminal cysteine residues required for proper subcellular protein localization. Additional RAB1A mutations, including two frameshift mutations and a mosaic missense mutation (c.83T>C [p.Leu28Pro]), were identified in three individuals with similar neurodevelopmental presentations. In rescue experiments, production of the full-length, but not the truncated, RAB1a rescued Golgi structure and cell proliferation in Rab1-depleted cells. In contrast, the missense-variant RAB1a disrupted Golgi structure despite intact Rab1 expression, suggesting a dominant-negative function of the mosaic missense mutation. Knock-down of RAB1A in cultured human embryonic stem cell-derived neurons resulted in impaired neuronal arborization. Finally, RAB1A is located within the 2p14-p15 microdeletion syndrome locus. The similar clinical presentations of individuals with RAB1A loss-of-function mutations and the 2p14-p15 microdeletion syndrome implicate loss of RAB1A in the pathogenesis of neurodevelopmental manifestations of this microdeletion syndrome. Our study identifies a RAB1A-related neurocognitive disorder with speech and motor delay, demonstrates an essential role for RAB1a in neuronal differentiation, and implicates RAB1A in the etiology of the neurodevelopmental sequelae associated with the 2p14-p15 microdeletion syndrome.
Topics: Child; Humans; Haploinsufficiency; Mutation; Mutation, Missense; rab GTP-Binding Proteins; Golgi Apparatus; Spastic Paraplegia, Hereditary
PubMed: 37924809
DOI: 10.1016/j.ajhg.2023.10.009 -
Frontiers in Veterinary Science 2023A 15-year-old spayed female domestic shorthaired cat was evaluated for chronic progressive paraparesis and proprioceptive ataxia. Neurological examination was consistent...
A 15-year-old spayed female domestic shorthaired cat was evaluated for chronic progressive paraparesis and proprioceptive ataxia. Neurological examination was consistent with a T3-L3 myelopathy. Plain thoracolumbar vertebral column radiographs and CT without intravenous contrast or myelography performed at another facility did not highlight any abnormalities. MRI of the thoracolumbar spinal cord identified an intraparenchymal space-occupying lesion extending from T10-T12. Surgery was performed to remove as much of the mass as possible, and to submit samples for histopathology. A dorsal laminectomy was performed over T9-T13. A midline myelotomy provided access to the mass, which was debrided with an intraoperative estimate of 80% removal. Histopathologic examination was consistent with a diagnosis of an astrocytoma. Post-operative treatment consisted of amoxicillin clavulanic acid, prednisolone, gabapentin, and additional analgesic medications in the direct post-operative period. Over the following 4 months, slow recovery of motor function was seen with continued physiotherapy. During the following 2 months, renal and cardiopulmonary disease were diagnosed and treated by other veterinarians. The cat was also reported to have lost voluntary movement in the pelvic limbs during this period, suggesting regression to paraplegia. Finally, 6 months post-surgery, the owner elected humane euthanasia. This is the second documentation of surgical treatment and outcome of an astrocytoma in the spinal cord of a cat.
PubMed: 37941813
DOI: 10.3389/fvets.2023.1264916 -
Cureus Apr 2024Spinal epidural abscess (SEA) can lead to a subacute onset of neurological deficits of the extremities and is commonly accompanied by spondylodiscitis if located...
Spinal epidural abscess (SEA) can lead to a subacute onset of neurological deficits of the extremities and is commonly accompanied by spondylodiscitis if located anterior to the dura. is a fish pathogen that is occasionally found in poultry, cattle, and swine. It is a rare cause of infection in humans. Most commonly it is associated with endocarditis. Until 2019, less than 30 cases of human infection have been published. To the best of our knowledge, we present the second reported case of SEA with spondylodiscitis caused by . How caused SEA, remains unclear in this case.
PubMed: 38721209
DOI: 10.7759/cureus.57827 -
Revista de La Facultad de Ciencias... Mar 2024Simultaneous spinal stenosis in three regions of the spine is an unusual condition that demands proper clinical evaluation and imaging. Currently, there are no... (Review)
Review
INTRODUCTION
Simultaneous spinal stenosis in three regions of the spine is an unusual condition that demands proper clinical evaluation and imaging. Currently, there are no established guidelines for its diagnostic and therapeutic approach.
OBJECTIVE
The objective of this study is to describe, based on a case report, the clinical presentation, treatment, and patient progression concerning triple stenosis, contrasting it with available evidence through a narrative review of the literature.
CASE PRESENTATION
A 69-year-old woman presented with a progressive paraparesis accompanied by right sciatica and positive signs of upper motor neuron involvement. Imaging confirmed triple stenosis: cervical, dorsal, and lumbar. Dorsal decompression and tumor resection were performed in association with conservative treatment for cervical and lumbar stenosis, resulting in a favorable evolution one year post-surgery.
CONCLUSION
Symptomatic triple-region spinal stenosis is an unusual condition. Proper clinical and radiological assessments will enable accurate diagnosis and timely management.
Topics: Humans; Spinal Stenosis; Retrospective Studies
PubMed: 38537092
DOI: 10.31053/1853.0605.v81.n1.43229 -
Genes Dec 2023Fatty acid hydroxylase-associated neurodegeneration (FAHN/SPG35) is caused by pathogenic variants in and has been linked to a continuum of specific motor and non-motor...
Fatty acid hydroxylase-associated neurodegeneration (FAHN/SPG35) is caused by pathogenic variants in and has been linked to a continuum of specific motor and non-motor neurological symptoms, leading to progressive disability. As an ultra-rare disease, its mutational spectrum has not been fully elucidated. Here, we present the prototypical workup of a novel variant, including clinical and in silico validation. An 18-year-old male patient presented with a history of childhood-onset progressive cognitive impairment, as well as progressive gait disturbance and lower extremity muscle cramps from the age of 15. Additional symptoms included exotropia, dystonia, and limb ataxia. Trio exome sequencing revealed a novel homozygous c.75C>G (p.Cys25Trp) missense variant in the gene, which was located in the cytochrome b5 heme-binding domain. Evolutionary conservation, prediction models, and structural protein modeling indicated a pathogenic loss of function. Brain imaging showed characteristic features, thus fulfilling the complete multisystem neurodegenerative phenotype of FAHN/SPG35. In summary, we here present a novel variant and provide prototypical clinical findings and structural analyses underpinning its pathogenicity.
Topics: Male; Humans; Adolescent; Mixed Function Oxygenases; Magnetic Resonance Imaging; Mutation; Heredodegenerative Disorders, Nervous System; Spastic Paraplegia, Hereditary
PubMed: 38275596
DOI: 10.3390/genes15010014