A prospective, observational study on conversion of clinically isolated syndrome to multiple sclerosis during 4-year period (MS NEO study) in Taiwan.

IMPORTANCE: CIS to MS conversion rates vary depending on population cohorts, initial manifestations, and durations of follow-up. OBJECTIVE: To investigate conversion rate of patients from CIS to MS and the prognostic significance of demographic and clinical variables in Taiwanese population. DESIGN: Nationwide, prospective, multi-centric, observational study from November 2008 to November 2014 with 4 years follow-up. SETTING: Multi-centre setting at 5 institutions in Taiwan. PARTICIPANTS: 152 patients having single clinical event potentially suggestive of MS in last 2 years were enrolled as consecutive sample. 33 patients were lost to follow-up and 16 patients did not complete the study.103 patients completed the study. INTERVENTION(S) (FOR CLINICAL TRIALS) OR EXPOSURE(S) (FOR OBSERVATIONAL STUDIES): Natural progression from first episode of CIS to MS or NMO was observed. MAIN OUTCOME(S) AND MEASURE(S): Variables analysed were 'proportion of patients converting to MS or NMO after first episode of CIS', 'duration between first episode of neurological event and diagnosis of MS', 'status of anti-AQP4 IgG' and 'length of longest contiguous spinal cord lesion in MS patients'. Association between baseline characteristics and progression to MS from CIS was analyzed using multiple logistic regression. Multivariate time dependent effect of baseline characteristics on progression to MS was plotted. RESULTS: 14.5% patients with CIS converted to MS after 1.1 ± 1.0 years with greater predisposition (18.8%) in those having syndromes referable to the cerebral hemispheres. Conversion rate from ON to MS was 9.7%. 90.9% patients had mild disease course. 46.7% patients had abnormal MRIs at baseline, with 0.6±0.5 contrast enhanced lesions. 'Below normal BMI' and 'MRI lesion load (≥ 4 lesions)' were identified as risk indicators for the development of MS. Amongst the patients who developed NMO as diagnosed by modern criteria, 80% were positive for anti-AQP4 IgG antibody. CONCLUSIONS AND RELEVANCE: 'Below normal BMI' and 'number of demyelinating lesions (≥4)' are significant predictors of conversion from CIS to MS. A low conversion rate to MS in Taiwanese CIS patients and majority of them having a mild course and minimal disability suggest the roles of geographic, genetic and ethnic factors. TRIAL REGISTRATION: Non-trial observational study.

Multiple sclerosis increases the risk of venous thromboembolism: a nationwide cohort analysis.

OBJECTIVES: The purpose of this study was to evaluate the effects of multiple sclerosis (MS) on the risk of venous thromboembolism (VTE) development. METHODS: We identified patients diagnosed with MS in Taiwan between 1998 and 2010 using the National Health Insurance Research Database and the Catastrophic Illness Patient Database (RCIPD). Each MS patient was frequency matched to 4 controls according to age, sex and the year of MS registration to the RCIPD. Patients with a history of VTE and incomplete information of age and sex were excluded. All patients were followed up from the index year until VTE diagnosis, loss to follow-up or the end of 2010. We calculated the hazard ratios (HRs) and 95% confidence intervals (CIs) of VTE in the MS and comparison cohorts using Cox proportional hazards regression models. RESULTS: We followed up 1238 MS patients and 4952 comparison patients for approximately 6437 and 27 595 person-years, respectively. After adjusting for age, sex and comorbidities, the MS patients exhibited a 6·87-fold increased risk of VTE compared with the control patients. Women with MS were associated with an 11·1-fold increased risk of VTE development compared with the non-MS women (95% CI: 2·70-45·5). The MS patients aged < 50 years exhibited a 14·8-fold increased risk of developing VTE compared with age-matched patients in the comparison cohort (95% CI: 2·99-73·4). The risk of VTE development increased with the duration of hospitalization stay. CONCLUSION: MS patients are associated with significantly greater risk of developing VTE compared with non-MS patients.

Clinical presentation and electrophysiological findings of porphyric neuropathies: a follow-up study.

INTRODUCTION: A case series of acute intermittent porphyria (AIP) is described that focuses on the clinical course of the disease with regard to neurological manifestations of the peripheral nervous system. METHODS: Eight patients were diagnosed with AIP on the basis of characteristic clinical findings, erythrocyte porphobilinogendeaminase activity, neuropathic patterns, serial changes in nerve conduction studies (NCS), and temporal relationship of central nervous system involvement. RESULTS: Six patients diagnosed with AIP<2 months after symptom onset had neuropathy that was predominantly upper extremity, motor, and proximal. NCS recovery rates were slower in the lower than the upper limbs. Two patients diagnosed >2 months after symptom onset had distal sensorimotor polyneuropathy. CONCLUSIONS: The findings from this case series suggest that the peripheral nerves may be differentially and selectively involved in different diagnostic stages of porphyric neuropathy.

Confusion or delirium in patients with posterior cerebral arterial infarction.

OBJECTIVE: To identify the possible anatomic sites and risk factors for the development of confusion or delirium in patients with posterior cerebral arterial (PCA) infarction. MATERIALS AND METHODS: Twenty-nine patients aged 34-86 years with PCA infarction were divided into two groups: one with and the other without perturbed mentation. The clinical and laboratory data, including neuroimages, were retrospectively reviewed. Student-t, chi-square and Fisher's exact tests were performed for data analysis. RESULTS: Confusion or delirium tended to develop in the left (10/13) or bilateral (5/5) PCA infarction as compared to the right PCA infarction (3/15) (P< 0.05) and medial occipital-temporal gyri involvement was crucial for its development (P< 0.05). The results were also noted in the patients with first-ever stroke. Diabetes mellitus was the sole biochemical factor to be associated with confusion or delirium (P< 0.01). CONCLUSIONS: The involvement of the medial occipito-temporal gyri, especially on the left side was the pivotal factor for the development of confusion or delirium in patients with PCA infarction. Higher prevalence of diabetes mellitus was also observed in the group with mental perturbation.

Acute hearing loss in a patient with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS).

The mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome is a rare congenital disorder of mitochondrial DNA. Patients with this syndrome may present acute onset of sensorineural hearing loss, which is genetic in origin. An impression of the MELAS syndrome is favored because hearing loss is part of the syndrome for some patients with epilepsy. We report a 20-year-old man who suffered from acute onset of bilateral hearing loss with epilepsy and two stroke-like events which recovered without any sequela. Epilepsy with complex partial seizures was controlled by antiepileptic drugs. Brain magnetic resonance images showed high signal lesions in bilateral temporal lobes. Serum levels of pyruvate and lactate were elevated. Muscle biopsy showed ragged-red fibers and molecular genetic study showed a point mutation of the mitochondrial A3243G gene. Mitochondrial disease with the MELAS syndrome was diagnosed and then he was treated with Co-enzyme Q10 and carnitine. The symptoms recovered gradually.

Characterization of MTM1 mutations in 31 Japanese families with myotubular myopathy, including a patient carrying 240 kb deletion in Xq28 without male hypogenitalism.

X-linked myotubular myopathy is a congenital muscle disorder due to MTM1 mutation, and is characterized clinically by generalized muscle weakness and hypotonia at birth usually resulting in early death. We newly identified 26 unrelated Japanese patients with MTM1 mutations by genomic DNA and transcript analysis, including 12 novel mutations. Among 31 patients, including our previously reported five patients, the c.1261-10A>G splice site mutation was the most frequent mutation. Three mutations, one missense and two splice site, were associated with milder phenotype. Of particular interest, one boy had a 240 kb deletion in Xq28 encompassing CXorf6 (formerly F18), MTM1 and MTMR1 but was not accompanied by hypogenitalism. CXorf6, which have been implicated in male sexual development, was not entirely deleted in this boy, resulting in the fusion with the MTMR1 gene. A chimeric fusion transcript was detected in patient's muscle by RT-PCR, suggesting this fusion gene product avoids the phenotype. This deletion led us to refine the critical region of CXorf6 for the development of male genitalia.