Multiple sclerosis (MS) is a chronic inflammatory demyelinating central nervous system disease that typically strikes young adults, especially women. The pathobiology of MS includes inflammatory and neurodegenerative mechanisms that affect both white and gray matter. These mechanisms underlie the relapsing, and often eventually progressive, course of MS, which is heterogeneous; confident prediction of long-term individual prognosis is not yet possible. However, because revised MS diagnostic criteria that incorporate neuroimaging data facilitate early diagnosis, most patients are faced with making important long-term treatment decisions, most notably the use and selection of disease-modifying therapy (DMT). Currently, there are 10 approved MS DMTs with varying degrees of efficacy for reducing relapse risk and preserving neurological function, but their long-term benefits remain unclear. Moreover, available DMTs differ with respect to the route and frequency of administration, tolerability and likelihood of treatment adherence, common adverse effects, risk of major toxicity, and pregnancy-related risks. Thorough understanding of the benefit-risk profiles of these therapies is necessary to establish logical and safe treatment plans for individuals with MS. We review the available evidence supporting risk-benefit profiles for available and emerging DMTs. We also assess the place of individual DMTs within the context of several different MS management strategies, including those currently in use (sequential monotherapy, escalation therapy, and induction and maintenance therapy) and others that may soon become feasible (combination approaches and "personalized medicine"). We conducted this review using a comprehensive search of MEDLINE, PubMed, EMBASE, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials, from January 1, 1990, to August 31, 2013. The following search terms were used: multiple sclerosis, randomized controlled trials, interferon-beta, glatiramer acetate, mitoxantrone, natalizumab, fingolimod, teriflunomide, dimethyl fumarate, BG-12, alemtuzumab, rituximab, ocrelizumab, daclizumab, neutralizing antibodies, progressive multifocal leukoencephalopathy.

Misdiagnosis of MS leads to unnecessary and potentially harmful risks to patients. Misinterpretation and misapplication of MS clinical and radiographic diagnostic criteria are important contemporary contributors to misdiagnosis.

We provide an overview of general competencies and specialty specific recommendations to serve as a foundation for medical schools to develop robust 4th-year curricula and for medical students to plan their 4th-year schedules.

No abstract

No abstract

Hemidiaphragms were removed from rats at various times after intrathoracic transection of the left phrenic nerve and were incubated in organ baths containing 1.5 ml of oxygenated, buffered physiologic saline solution, with added glucose and bovine serum albumin. After incubation, the acetylcholinesterase (AChE: EC 3.1.1.7) activities of the bath fluid and of the muscle were determined. Innervated left hemidiaphragms were found to release 107 units of AChE over a 3-h period, corresponding to 1.9% of their total AChE activity. Denervation led to a rapid loss of AChE from the muscle coincident with a transient increase in the outpouring of enzyme activity into the bath fluid. Thus, 1 day after nerve transection the left hemidiaphragm contained only 68% of the control amounts of AChE activity, but released 140% as much as control. After 3 or 4 days of denervation, the AChE activity of the diaphragm stabilized at 35% of the control value. Release also fell below control by this time, but not as far. One week after denervation the release, 69 units per 3 hr, correspond to 3.3% of the reduced content of AChE activity in the muscle, indicating that denervation caused an increase in the proportion of AChE released. Sucrose density gradient ultracentrifugation showed that 10S AChE accounted for more than 80% of the released enzyme activity at all times. The results did not rule out the possibility, however, that the released enzyme originally stemmed from 4S or 16S AChE in the diaphragms.

The role of VEPs in evaluating patients with neurologic disease has evolved in an era of advanced neuroimaging techniques. MRI is clearly superior in sensitivity and specificity to VEPs in detecting retrochiasmatic lesions. However, in patients with lesions involving the optic nerve and anterior chiasm, VEPs have several important advantages: (1) VEPs are objective and reproducible and may demonstrate a functional abnormality that is not evident on physical examination or with neuroimaging studies; (2) VEP abnormalities may persist over time even when there is clinical resolution of visual symptoms; (3) VEPs may be a more reliable indicator of disease than MRI (MRI may reveal nonspecific abnormalities that do not represent a pathologic process, such as nonspecific white matter signal changes in the cerebral hemispheres); (4) VEPs may be more sensitive than MRI for detecting abnormalities in optic nerves; and (5) VEP studies are less expensive than MRI studies and can be used in situations where MRI studies are contraindicated (i.e., pacemakers, aneurysm clips, etc).

Although multiple sclerosis primarily affects myelin within the central nervous system, both pathologic and physiological studies suggest that mild deficits in peripheral nervous system myelin may be common. To evaluate this question further, we performed near nerve studies on sural nerves of 14 patients with multiple sclerosis. Peak-to-peak amplitude and maximum conduction velocity were normal in 9 of 14 patients, while minimum conduction velocity, or the velocity of the slowest-conducting component of the sensory action potential, was abnormally reduced in 9 patients. In addition, the supernormal period was evaluated for patients and compared with a control sample; multiple sclerosis patients showed a significant reduction in the amplitude of supernormality. Both the reduction in minimum conduction velocity and the alteration in the supernormal period are consistent with a mild defect in peripheral myelin.