ABSTRACT
OBJECTIVE: Recessive mutations in the CAPN1 gene have recently been identified in spastic paraplegia 76 (SPG76), a complex hereditary spastic paraplegia (HSP) that is combined with cerebellar ataxia, resulting in an ataxia-spasticity disease spectrum. This study aims to assess the influence of CAPN1 variants on the occurrence of SPG76 and identify factors potentially contributing to phenotypic heterogeneity. METHODS: We screened a cohort of 240 unrelated HSP families for variants in CAPN1 using high-throughput sequencing analysis. We described in detail the clinical and genetic features of the SPG76 patients in our cohort and summarized all reported cases. RESULTS: Six unreported CAPN1-associated families containing eight patients with or without cerebellar ataxia were found in our cohort of HSP cases. These patients carried three previously reported homozygous truncating mutations (p.V64Gfs* 103, c.759+1G>A, and p.R285* ), and three additional novel compound heterozygous missense mutations (p.R481Q, p.P498L, and p.R618W). Lower limbs spasticity, hyperreflexia, and Babinski signs developed in about 94% of patients, with ataxia developing in 63% of cases. In total, 33 pathogenic mutations were distributed along the three reported functional domains of calpain-1 protein, encoded by CAPN1, with no hotspot region. A comparison of gender distribution between the two groups indicated that female SPG76 patients were significantly more likely to present with complicated HSP than male patients (P = 0.015). INTERPRETATION: Our study supports the clinically heterogeneous inter- and intra-family variability of SPG76 patients, and demonstrates that gender and calpain-1 linker structure may contribute to clinical heterogeneity in SPG76 cases.
Subject(s)
Calpain/genetics , Cerebellar Ataxia/genetics , Mutation/genetics , Phenotype , Spastic Paraplegia, Hereditary/genetics , Ataxia/genetics , Female , Humans , Intellectual Disability/virology , Male , Muscle Spasticity/virology , Optic Atrophy/virology , Paraplegia/genetics , Pedigree , Spinocerebellar Ataxias/virologyABSTRACT
We investigate the possible effects of acupuncture on the improvement of neurological problems in HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP)disease. Twenty patients with HAM/TSP were studied in this pre and post-test clinical trial. Urinary incontinence, global motor disability, spasticity, and pain severity were evaluated before, one month, and three-month after the intervention. Analyses demonstrated a significant reduction of urinary symptoms one month after acupuncture (P = 0.023). A significant improvement was observed in patients' pain and the spasticity at the upper extremity joints, one and three-month after the intervention (P < 0.05). This study suggests that body acupuncture can be used as a complementary treatment to improve HAM/TSP neurological symptoms.
Subject(s)
Acupuncture Therapy/methods , HTLV-I Infections/therapy , Human T-lymphotropic virus 1/pathogenicity , Muscle Spasticity/therapy , Pain Management/methods , Paraparesis, Tropical Spastic/therapy , Urinary Incontinence/therapy , Adult , Female , HTLV-I Infections/physiopathology , HTLV-I Infections/virology , Human T-lymphotropic virus 1/growth & development , Humans , Male , Middle Aged , Muscle Spasticity/physiopathology , Muscle Spasticity/virology , Pain/physiopathology , Pain/virology , Paraparesis, Tropical Spastic/physiopathology , Paraparesis, Tropical Spastic/virology , Severity of Illness Index , Treatment Outcome , Urinary Incontinence/physiopathology , Urinary Incontinence/virologySubject(s)
Paraparesis, Tropical Spastic/pathology , Paraparesis, Tropical Spastic/physiopathology , Spinal Cord/pathology , Spinal Cord/physiopathology , Afferent Pathways/pathology , Afferent Pathways/physiopathology , Afferent Pathways/virology , Antigens, Viral/immunology , Disease Progression , Female , Gait Disorders, Neurologic/pathology , Gait Disorders, Neurologic/physiopathology , Gait Disorders, Neurologic/virology , Humans , Magnetic Resonance Imaging , Middle Aged , Muscle Spasticity/pathology , Muscle Spasticity/physiopathology , Muscle Spasticity/virology , Sensation Disorders/pathology , Sensation Disorders/physiopathology , Sensation Disorders/virology , Spinal Cord/virology , Urinary Bladder, Neurogenic/pathology , Urinary Bladder, Neurogenic/physiopathology , Urinary Bladder, Neurogenic/virology , Viral Load/immunologySubject(s)
HIV Infections/complications , HIV-1/immunology , Motor Neuron Disease/genetics , Motor Neuron Disease/virology , Adult , Disease Progression , Dysarthria/genetics , Dysarthria/physiopathology , Dysarthria/virology , Gait Disorders, Neurologic/genetics , Gait Disorders, Neurologic/physiopathology , Gait Disorders, Neurologic/virology , HIV-1/genetics , Humans , Immunocompromised Host/genetics , Immunocompromised Host/immunology , Male , Middle Aged , Motor Cortex/immunology , Motor Cortex/physiopathology , Motor Cortex/virology , Motor Neuron Disease/physiopathology , Motor Neurons/immunology , Motor Neurons/virology , Muscle Spasticity/genetics , Muscle Spasticity/physiopathology , Muscle Spasticity/virology , Paraparesis/genetics , Paraparesis/physiopathology , Paraparesis/virology , Pyramidal Tracts/immunology , Pyramidal Tracts/physiopathology , Pyramidal Tracts/virologyABSTRACT
People with human T-cell lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) develop spasticity. The authors examined 34 patients with HAM/TSP in Perú using a device that measures tone in the gastroc-soleus-Achilles tendon unit and provides a quantitative spasticity assessment (QSA). Tone in the 34 patients was more than double that of women with asymptomatic HTLV-I infection. The device may help to track progression in HTLV-I infection.
Subject(s)
HTLV-I Infections/complications , Muscle Spasticity/physiopathology , Muscle Spasticity/virology , Paraparesis, Tropical Spastic/physiopathology , Paraparesis, Tropical Spastic/virology , Adult , Female , Human T-lymphotropic virus 1 , Humans , Male , Middle AgedABSTRACT
The pathogenesis of AIDS-associated vacuolar myelopathy (VM) may be related to abnormality of transmethylation mechanisms in the nervous system. To evaluate the safety and potential efficacy of the methyl-group donor L-methionine in AIDS-associated VM, we conducted a pilot clinical trial in 12 patients with VM. Seven of the nine patients who completed the study had clinical and electrophysiologic improvement. Controlled studies may be indicated to assess the efficacy and safety of L-methionine in AIDS-associated VM.
Subject(s)
Acquired Immunodeficiency Syndrome/complications , Metabolic Diseases/virology , Methionine/administration & dosage , Spinal Cord Diseases/drug therapy , Spinal Cord Diseases/etiology , Acquired Immunodeficiency Syndrome/metabolism , Adult , Erectile Dysfunction/virology , Evoked Potentials , Female , Humans , Male , Metabolic Diseases/drug therapy , Metabolic Diseases/enzymology , Methionine/metabolism , Middle Aged , Muscle Spasticity/diagnosis , Muscle Spasticity/drug therapy , Muscle Spasticity/virology , Pilot Projects , Spinal Cord Diseases/pathology , Urination , Vacuoles/pathologyABSTRACT
DNA from Epstein-Barr virus (EBV) Types A, B and Herpesvirus-6 (HHV-6) Variants A and B was detected by the Polymerase chain reaction (PCR) in the saliva of 51 non-immunocompromised donor patients and in the blood of seventy non-immunocompromised donor patients with specific signs and symptoms. The minimum selection criteria for each patient included acute or recurrent upper respiratory infection, unilateral thoracolumbar muscle spasm and fatigue. PCR DNA detection in the saliva of selected donors revealed 80% of the donors had either Type A or B EBV (41 of 51), 34.1% Type B EBV only (14 of 41), 9% Type A only (4 of 41), and 56.1% Type A and B EBV (23 of 41). HHV-6 DNA was detected in 45.0% (23 of 51). PCR for EBV in blood of selected donors revealed 68.5% Type A or B EBV (48 of 70), 0% type B EBV alone, 64.8% Type A EBV only (31 of 48) and 35.4% both Type A and B EBV (17 of 48). HHV-6 was detected in 96.4% (64 of 70). The association of Type B EBV in the pathogenesis of these patients is explored based on the PCR quantitation of B type EBV DNA present in the samples.