Faculty Bibliography

BACKGROUND AND OBJECTIVES: Diagnosis of multiple sclerosis (MS) requires exclusion of diseases that could better explain the clinical and paraclinical findings. A systematic process for exclusion of alternative diagnoses has not been defined. An International Panel of MS experts developed consensus perspectives on MS differential diagnosis. METHODS: Using available literature and consensus, we developed guidelines for MS differential diagnosis, focusing on exclusion of potential MS mimics, diagnosis of common initial isolated clinical syndromes, and differentiating between MS and non-MS idiopathic inflammatory demyelinating diseases. RESULTS: We present recommendations for 1) clinical and paraclinical red flags suggesting alternative diagnoses to MS; 2) more precise definition of "clinically isolated syndromes" (CIS), often the first presentations of MS or its alternatives; 3) algorithms for diagnosis of three common CISs related to MS in the optic nerves, brainstem, and spinal cord; and 4) a classification scheme and diagnosis criteria for idiopathic inflammatory demyelinating disorders of the central nervous system. CONCLUSIONS: Differential diagnosis leading to MS or alternatives is complex and a strong evidence base is lacking. Consensus-determined guidelines provide a practical path for diagnosis and will be useful for the non-MS specialist neurologist. Recommendations are made for future research to validate and support these guidelines. Guidance on the differential diagnosis process when MS is under consideration will enhance diagnostic accuracy and precision.

Multiple sclerosis is a common demyelinating disorder of the central nervous system, and neuro-ophthalmologic manifestations occur in the majority of patients. This article provides a review of the pathogenesis, epidemiology, and classification of multiple sclerosis. Neuro-ophthalmologic abnormalities associated with multiple sclerosis, including acute demyelinating optic neuritis and internuclear ophthalmoplegia, are described in detail. Current and emerging technologies designed to assess visual function in multiple sclerosis are discussed. A summary presents the appropriate evaluation and management of patients with optic neuritis and other first demyelinating events (also referred to as clinically isolated syndromes).

PURPOSE: Obesity and weight gain are known risk factors for idiopathic intracranial hypertension (IIH; or pseudotumor cerebri). The authors examined profiles of body mass index (BMI) and patterns of weight gain associated with IIH. They also examined vision-specific health-related quality of life (HRQOL) in newly diagnosed IIH patients and explored the relative contribution of obesity and weight gain to overall HRQOL in this disorder. DESIGN: Matched case-control study. METHODS: Female patients with newly diagnosed IIH (n = 34) and other neuro-ophthalmologic disorders (n = 41) were enrolled in a case-control study to assess patterns of self-reported weight gain. The HRQOL was examined using the 25-Item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) and the SF-36 Health Survey (Physical Components Summary and Mental Components Summary [MCS]). RESULTS: Higher BMIs were associated with greater risk of IIH (P = .003, logistic regression analysis adjusting for case-control matching), as were higher percentages of weight gain during the year before symptom onset (P = .004). Moderate weight gain (5% to 15%) was associated with a greater risk of IIH among both obese and nonobese patients. Obesity and weight gain influenced the relation between HRQOL and IIH only for subscale scores reflecting mental health (SF-36 MCS). The NEI-VFQ-25 and SF-36 subscale scores were lower in IIH compared with other neuro-ophthalmologic disorders and published norms. CONCLUSIONS: Higher levels of weight gain and BMI are associated with greater risk of IIH. Even nonobese patients (BMI <30) are at greater risk for IIH in the setting of moderate weight gain. Vision-specific and overall HRQOL are affected to a greater extent in IIH than in other neuro-ophthalmologic disorders.

OBJECTIVE: To report the relationship between disease activity and health-related quality of life (HRQoL) in relapsing multiple sclerosis, and the impact of natalizumab. METHODS: HRQoL data were available from 2,113 multiple sclerosis patients in natalizumab clinical studies. In the Natalizumab Safety and Efficacy in Relapsing Remitting Multiple Sclerosis (AFFIRM) study, patients received natalizumab 300 mg (n = 627) or placebo (n = 315); in the Safety and Efficacy of Natalizumab in Combination with Interferon Beta-1a in Patients with Relapsing Remitting Multiple Sclerosis (SENTINEL) study, patients received interferon beta-1a (IFN-beta-1a) plus natalizumab 300 mg (n = 589), or IFN-beta-1a plus placebo (n = 582). The Short Form-36 (SF-36) and a subject global assessment visual analog scale were administered at baseline and weeks 24, 52, and 104. Prespecified analyses included changes from baseline to week 104 in SF-36 and visual analog scale scores. Odds ratios for clinically meaningful improvement or worsening on the SF-36 Physical Component Summary (PCS) and Mental Component Summary were calculated. RESULTS: Mean baseline SF-36 scores were significantly less than the general US population and correlated with Expanded Disability Status Scale scores, sustained disability progression, relapse number, and increased volume of brain magnetic resonance imaging lesions. Natalizumab significantly improved SF-36 PCS and Mental Component Summary scores at week 104 in AFFIRM. PCS changes were significantly improved by week 24 and at all subsequent time points. Natalizumab-treated patients in both studies were more likely to experience clinically important improvement and less likely to experience clinically important deterioration on the SF-36 PCS. The visual analog scale also showed significantly improved HRQoL with natalizumab. INTERPRETATION: HRQoL was impaired in relapsing multiple sclerosis patients, correlated with severity of disease as measured by neurological ratings or magnetic resonance imaging, and improved significantly with natalizumab.

Papilledema is an uncommon presentation of spinal cord processes. Spinal subdural abscess (SSA) is a rare site of post-operative infection. We report a patient who developed papilledema as the primary manifestation of a post-operative lumbar subdural abscess. A spinal abscess should be considered in the post-operative spinal surgery patient who develops papilledema in the setting of persistent back pain. The increased intracranial pressure associated with lumbar spinal cord abscess most likely results from a markedly elevated cerebrospinal fluid (CSF) protein or the disruption of CSF flow in the spinal cul-de-sac.

Supranuclear gaze palsies are an uncommon feature of Creutzfeldt-Jakob disease (CJD). Most reported cases of CJD with features of supranuclear gaze palsy are familial. We report 2 patients with supranuclear vertical gaze abnormalities associated with spongiform changes in the midbrain. Both patients were found to have sporadic CJD after genetic testing. Distinguishing familial from sporadic CJD in this setting has important genetic and epidemiological implications.