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.

Lambert-Eaton myasthenic syndrome associated with alemtuzumab administration.

BACKGROUND: Alemtuzumab administration is known to cause secondary autoimmune disease but has not been associated with the development of neurologic autoimmune conditions. Lambert-Eaton myasthenic syndrome (LEMS) is caused by autoantibodies directed against calcium channels on the neuromuscular junction. CASE REPORT: We report a case of a patient with relapsing-remitting multiple sclerosis (RRMS) treated with alemtuzumab who develop generalized weakness initially attributed to progression of MS but eventually determined to be due to LEMS. CONCLUSION: Alemtuzumab treatment can result in the development of neurologic autoimmune conditions that could mimic MS progression.

Acute inflammatory demyelinating optic neuritis: evidence-based visual and neurological considerations.

BACKGROUND: Optic neuritis (ON) is an acute inflammatory demyelinating disorder of the optic nerve that occurs most often in young adults. It can be a monophasic or polyphasic disease isolated to the optic nerve(s) or can be associated with a more widespread demyelinating disorder of the central nervous system such as multiple sclerosis (MS) or neuromyelitis optica. Advances in therapeutics that modify the risk of progression to MS have emphasized accurate diagnosis and risk assessment of patients with ON. REVIEW SUMMARY: ON usually presents with acute unilateral visual loss associated with ocular pain exacerbated by eye movements. Similar to results found in studies assessing corticosteroid used in MS relapses, intravenous methylprednisolone accelerates visual recovery from ON but has no impact on long-term visual outcome. A clinically isolated syndrome (CIS), such as ON, is a clinical demyelinating event that is often the initial attack of relapsing-remitting MS. Disease modifying drugs, in particular interferons-beta, have been shown to reduce the risk of MS conversion in high-risk patients presenting with a CIS. The exact timing and patient selection for the initiation of treatment remain controversial. CONCLUSION: ON is the best studied CIS. The visual prognosis is excellent in most cases regardless of whether the patient is treated with corticosteroids or not. Three recently completed prospective, randomized, double-blinded, placebo-controlled studies have shown that starting a disease-modifying drug at the time of a CIS can reduce the rate of development of MS. However, better diagnostic tools are needed to precisely predict the conversion to MS and the factors influencing disease severity to determine the most appropriate therapeutic paradigm and avoid unnecessary treatment.