Hypertension, cerebral Amyloid, aGe Associated Known neuroimaging markers of cerebral small vessel disease Undertaken with stroke REgistry (HAGAKURE) prospective cohort study: Baseline characteristics and association of cerebral small vessel disease with prognosis in an ischemic stroke cohort.

Introduction: Cerebral small vessel disease (SVD) is one of the leading causes of stroke; each neuroimaging marker of SVD is correlated with vascular risk factors and associated with poor prognosis after stroke. However, longitudinal studies investigating the association between comprehensive SVD burden scoring system, "total SVD score" - which encompasses the established neuroimaging markers of lacunae, cerebral microbleeds (CMBs), white matter hyperintensities (WMH) including periventricular hyperintensities, and perivascular spaces in basal ganglia- and clinical outcomes are limited. The aim of this study is to determine the association between SVD burden and long-term prognosis in patients with ischemic stroke. Methods and design: This prospective, single-center, observational study enrolled patients with acute ischemic stroke, including cerebral infarction and transient ischemic attack. Magnetic resonance imaging scans were performed, and then total SVD score (range, 0-4) was calculated. We recorded baseline characteristics and evaluated the relationships of long-term outcomes to SVD neuroimaging markers and total SVD score. Stroke recurrence was thought as primary outcome. Hazard ratios (HRs) of events during follow-up were calculated using Cox proportional hazards modeling with adjustments for age, sex, hypertension, dyslipidemia, diabetes mellitus, atrial fibrillation, and smoking. Cumulative event rates were estimated using the Kaplan-Meier method. Results: Consecutive 564 acute ischemic stroke patients were enrolled according to inclusion and exclusion criteria. A total of 467 participants with first-ever ischemic stroke were analyzed (median age 75.0 [interquartile range, 64.0-83.0] years, 59.3% male). Total SVD score was 0 point in 47 individuals (12.0%), 1 point in 83 (21.2%), 2 points in 103 (26.3%), 3 points in 85 (21.7%), and 4 points in 73 (18.7%). Twenty-eight recurrent stroke events were identified during follow-up. Total SVD score ≥ 2, presence of CMBs, and moderate-to-severe WMH were associated with increased risk of recurrent stroke events (HR 9.31, 95% confidence interval [CI] 2.33-64.23; HR 2.81, 95% CI 1.08-7.30; HR 2.90, 95% CI 1.22-6.88, respectively). Conclusion: The accumulation of SVD biomarkers as determined by total SVD score offered a reliable predictor of stroke recurrence. This study established a firm understanding of SVD prognosis in clinical settings.

Incidence and clinical significances of human T-cell lymphotropic virus type I-associated myelopathy with T2 hyperintensity on spinal magnetic resonance images.

OBJECTIVE: To clarify the incidence and clinical significance of HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP) showing T2 hyperintensity in the spinal cord on magnetic resonance images (MRI). PATIENTS AND METHODS: We reviewed the spinal cord MRI of 38 HAM/TSP patients and analyzed them in relation to clinical and laboratory findings. Analyzed data were: age at onset, disease duration, disability status, responsiveness to interferon therapy, brain abnormalities on MRI, serum anti-HTLV-I titers, and cerebrospinal fluid (CSF) findings. RESULTS: MRI findings of the spinal cord were classified into 3 types, "normal" (n=22, 57.9%), "atrophy" (n=13, 34.2%) and "T2-hyperintensity" (n=3, 7.9%). Patients in the normal and atrophy types showed slowly progressive paraparesis. Significant differences were not found between the normal and atrophy types in any clinical or laboratory data, including disease duration, disability status and responsiveness to interferon-alpha therapy. Meanwhile, all patients showing T2-hyperintensity had severe paraparesis of a rapid progressive nature, with CSF IgG elevation. CONCLUSION: HAM/TSP with T2-hyperintensity on spinal MRI shows a rapid progressive clinical course with severe motor impairment. The incidence of this malignant form of HAM/TSP is estimated to be around 7.9%.

[Clinical characteristics, diagnostic criteria and treatment of progressive multifocal leukoencephalopathy].

The clinical characteristics, diagnostic criteria and treatment of progressive multifocal leukoencephalopathy (PML) are reviewed. PML is characterized by rapid progression and poor outcome, and therefore requires the diagnosis and treatment as early as possible. Diffusion-weighted and diffusion tensor MRI were reported to be useful for the evaluation of disease activity of PML. The detection of JCV-DNA in the cerebrospinal fluid by PCR has replaced the brain biopsy. Highly active antiretroviral therapy has improved both the survival rate and the neurological functions in HIV-associated PML. However, the treatment for immune reconstitution inflammatory syndrome, which often deteriorates neurological functions, has never been solved.

Diffuse cranial nerve and cauda equina lesions associated with breast cancer.

We report on the case of a patient with breast cancer with diffuse cranial nerve and cauda equina lesions. Magnetic resonance imaging of the patient's brain and spinal cord showed diffuse abnormal enhancement and slight enlargement of the cranial nerves and cauda equina. Although the results of subsequent testing for two antineural antibodies were negative, paraneoplastic sensorimotor neuropathy associated with breast cancer was considered to be the most likely clinical diagnosis.

Four mutations of the spastin gene in Japanese families with spastic paraplegia.

Hereditary spastic paraplegia (HSP) is a group of genetically heterogeneous neurodegenerative disorders characterized by slowly progressive spasticity and weakness of the lower limbs. HSP is caused by failure of development or selective degeneration of the corticospinal tracts, which contain the longest axons in humans. The most common form of HSP is caused by mutations of the spastin gene (SPAST), located on chromosome 2p21-p22, which encodes spastin, one of the ATPases associated with diverse cellular activities (AAA). In this study, we detected four causative mutations of SPAST among 14 unrelated patients with spastic paraplegia. Two missense mutations (1447A-->G, 1207C-->G) and two deletion mutations (1465delT, 1475-1476delAA) were located in the AAA cassette region. Three of these four mutations were novel. Previous reports and our results suggest that the frequency of SPAST mutations is higher among Japanese patients with autosomal dominant HSP, although SPAST mutations are also observed in patients with sporadic spastic paraplegia.