Novel CAPN1 mutations extend the phenotypic heterogeneity in combined spastic paraplegia and ataxia.

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.

Acupuncture in the treatment of HTLV-I-associated myelopathy / tropical spastic Paraparesis.

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.

Quantitative assessment of spasticity in human T-cell lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis.

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.

A pilot study of L-methionine for the treatment of AIDS-associated myelopathy.

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.

Epstein-Barr virus (herpesvirus 4) types A, B and herpesvirus-6 variants A and B in patients presenting with recurrent upper respiratory inflammation, persistent paravertebral thoraco-lumbar muscle spasm and fatigue by polymerase chain reaction (PCR).

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.