Onset of progressive phase is an age-dependent clinical milestone in multiple sclerosis.

BACKGROUND: It is unclear if all patients with relapsing-remitting multiple sclerosis (RRMS) ultimately develop progressive MS. Onset of progressive disease course seems to be age- rather than disease duration-dependent. Some forms of progressive MS (e.g. primary progressive MS (PPMS)) are uncommon in population-based studies. Ascertainment of patients with PPMS from clinic-based populations can facilitate a powerful comparison of age at progression onset between secondary progressive MS (SPMS) and PPMS but may introduce unclear biases. OBJECTIVE: Our aim is to confirm that onset of progressive disease course is more relevant to the patient's age than the presence or duration of a pre-progression relapsing disease course in MS. METHODS: We studied a population-based MS cohort (n=210, RRMS n=109, progressive MS n=101) and a clinic-based progressive MS cohort (n=754). Progressive course was classified as primary (PPMS; n=322), single attack (SAPMS; n=112) and secondary progressive (SPMS; n=421). We studied demographics (chi(2) or t-test), age-of-progression-onset (t-test) and time to Expanded Disability Status Scale of 6 (EDSS6) (Kaplan-Meier analyses). RESULTS: Sex ratio (p=0.58), age at progression onset (p=0.37) and time to EDSS6 (p=0.16) did not differ between the cohorts. Progression had developed before age 75 in 99% of patients with known progressive disease course; 38% with RRMS did not develop progression by age 75. Age at progression onset did not differ between SPMS (44.9±9.6), SAPMS (45.5±9.6) and PPMS (45.7±10.8). In either cohort, only 2% of patients had reached EDSS6 before onset of progression. CONCLUSIONS: Patients with RRMS do not inevitably develop a progressive disease course. Onset of progression is more dependent on age than the presence or duration of a pre-progression symptomatic disease course. Moderate disability is sustained predominantly after the onset of a progressive disease course in MS.

Alpha-lipoic acid may improve symptomatic diabetic polyneuropathy.

OBJECTIVE: In patients with symptomatic diabetic polyneuropathy, is oral alpha-lipoic acid (ALA) effective in improving neuropathic symptoms compared with placebo? METHODS: The question was addressed with a structured evidence-based clinical neurologic practice review via videoconferencing between 3 academic institutions. Participants included consultant and resident neurologists, clinical epidemiologists, medical librarians, and clinical content experts. A critically appraised topic format was employed, with a clinical scenario, structured question, search strategy, appraisal, results, summary of evidence, commentary, and bottom-line conclusions. RESULTS: A single modestly valid randomized controlled trial demonstrated that oral ALA in doses of 600 mg, 1200 mg, and 1800 mg was effective in reducing neuropathic symptoms of diabetic distal symmetric polyneuropathy (DSP) at 5 weeks, as assessed by the Total Symptom Score (>or=50% reduction), with number needed to treat (NNT) (95% CI) of 2.7 (1.8 to 5.8), 4.1 (2.3 to 20.2), and 3.2 (2.0 to 8.6), respectively. Adverse events, including nausea, vomiting, and vertigo, were identified but occurred most frequently with ALA doses of 1200 mg and 1800 mg. Overall, treatment emergent adverse events for ALA 600 mg were not significantly different than placebo, but ALA 1200 mg and 1800 mg had number needed to harm (95% CI) of 4.5 (2.4 to 31.0) and 3.0 (1.9 to 7.1), respectively. CONCLUSION: Oral ALA may improve neuropathic symptoms in diabetic DSP. A single modestly valid RCT demonstrated that 600 mg was an effective and well-tolerated dose, with NNT 2.7 to significantly reduce neuropathic pain symptoms over a 5-week period. ALA's role and place in an algorithm among other commonly prescribed oral treatments for symptomatic relief of neuropathic pain in diabetic DSP remains unclear.

Acute demyelinating disorders: emergencies and management.

Central nervous system (CNS) inflammatory demyelinating diseases are a group of disorders that include multiple sclerosis, acute disseminated encephalomyelitis, and neuromyelitis optica. These conditions may result in emergencies because of severe inflammatory destruction of CNS tissues or complications thereof. Most of these conditions are responsive to appropriate therapy and early diagnosis and treatment leads to better outcomes. We discuss the spectrum of emergencies associated with these disorders, as well as clinical features, investigations, and management.

Major basic protein homolog (MBP2): a specific human eosinophil marker.

Human eosinophil granule major basic protein (MBP1) is an exceedingly basic (isoelectric point >11) 14-kDa protein, comprising the core of the secondary eosinophil granule. Recently, a less cationic homolog of MBP, termed MBPH or simply, MBP2, has been discovered. We prepared a panel of mAbs to MBP2 and used these Abs to localize and quantitate this molecule in leukocytes and biological fluids. Specific mAbs for MBP2 were selected using slot-blot analyses and used in a two-site immunoassay, Western blotting, and immunofluorescence microscopy. The sensitivity of the immunoassay was markedly improved by reduction and alkylation of MBP2. MBP1 is more abundant than MBP2 in lysates of eosinophils and their granules, as judged by immunoassay and Western blotting. By immunofluorescence, MBP1 is present in eosinophils, basophils, and a human mast cell line (HMC1), whereas MBP2 is only detected in eosinophils. Neither MBP1 nor MBP2 could be detected in any other peripheral blood leukocyte. MBP2 levels measured in plasma and serum were essentially identical. In contrast to past measurements for MBP1, MBP2 was not detected above normal levels in sera from pregnant donors. However, measurement of serum MBP2 discriminated patients with elevated eosinophils from normal subjects, and MBP2 was also detectable in other biological specimens, such as bronchoalveolar lavage, sputum, and stool. These results indicate that MBP2 is present only in eosinophils and that it may be a useful biomarker for eosinophil-associated diseases.