Rebecca Spain

Body-worn motion sensors detect balance and gait deficits in people with multiple sclerosis who have normal walking speed.

While balance and gait limitations are hallmarks of multiple sclerosis (MS), standard stopwatch-timed measures practical for use in the clinic are insensitive in minimally affected patients. This prevents early detection and intervention for mobility problems. The study sought to determine if body-worn sensors could detect differences in balance and gait between people with MS with normal walking speeds and healthy controls. Thirty-one MS and twenty-eight age- and sex-matched control subjects were tested using body-worn sensors both during quiet stance and gait (Timed Up and Go test, TUG). Results were compared to stopwatch-timed measures. Stopwatch durations of the TUG and Timed 25 Foot Walk tests were not significantly different between groups. However, during quiet stance with eyes closed, people with MS had significantly greater sway acceleration amplitude than controls (p=0.02). During gait, people with MS had greater trunk angular range of motion in roll (medio-lateral flexion, p=0.017) and yaw (axial rotation, p=0.026) planes. Turning duration through 180° was also longer in MS (p=0.031). Thus, body-worn motion sensors detected mobility differences between MS and healthy controls when traditional timed tests could not. This portable technology provides objective and quantitative mobility data previously not obtainable in the clinic, and may prove a useful outcome measure for early mobility changes in MS.

Optical coherence tomography angiography of optic nerve head and parafovea in multiple sclerosis

Aims To investigate swept-source optical coherence tomography (OCT) angiography in the optic nerve head (ONH) and parafoveal regions in patients with multiple sclerosis (MS). Methods Fifty-two MS eyes and 21 healthy control (HC) eyes were included. There were two MS subgroups: 38 MS eyes without an optic neuritis (ON) history (MS −ON), and 14 MS eyes with an ON history (MS +ON). The OCT images were captured by high-speed 1050 nm swept-source OCT. The ONH flow index (FI) and parafoveal FI were quantified from OCT angiograms. Results The mean ONH FI was 0.160±0.010 for the HC group, 0.156±0.017 for the MS−ON group, and 0.140±0.020 for the MS+ON group. The ONH FI of the MS+ON group was reduced by 12.5% compared to HC eyes (p=0.004). A higher percentage of MS+ON eyes had abnormal ONH FI compared to HC patients (43% vs 5%, p=0.01). Mean parafoveal FIs were 0.126±0.007, 0.127±0.010, and 0.129±0.005 for the HC, MS−ON, and MS +ON groups, respectively, and did not differ significantly among them. The coefficient of variation (CV) of intravisit repeatability and intervisit reproducibility were 1.03% and 4.53% for ONH FI, and 1.65% and 3.55% for parafoveal FI. Conclusions Based on OCT angiography, the FI measurement is feasible, highly repeatable and reproducible, and it is suitable for clinical measurement of ONH and parafoveal perfusion. The ONH FI may be useful in detecting damage from ON and quantifying its severity.

Inflammatory neurological disease in patients treated with tumor necrosis factor alpha inhibitors

Background: TNF alpha inhibitor (TNFAI) therapy has been associated with inflammatory neurological syndromes. Objectives: To present 10 new cases of TNFAI associated neurological disease and a review of the literature. Methods: The design and methods were based on case series collected from Oregon Health & Sciences University and the Department of Veterans Affairs Hospital in Portland, Oregon and PubMed review. Results: We describe eight demyelinating central nervous system syndromes and two peripheral nervous system syndromes associated with TNFAI therapy. Characteristics from these cases are analyzed with data from 141 additional cases from the literature. Onset was between the ages of 36 and 65 years in 84% of CNS cases, distinguishing TNFAI-associated disease from sporadic multiple sclerosis. Symptoms occurred within one year of TNFAI therapy in 71%. Etanercept therapy was reported in the majority of cases of CNS syndromes and infliximab therapy in the majority of neuromuscular syndromes. Significant disability remained in 67% of cases although 82% had been followed for less than one year. Conclusions: Our case series and literature review demonstrates an association between TNFAI therapy and inflammatory neurological disease. While a causal relationship is suggested, this remains uncertain. TNFAI-associated neurological syndromes are associated with significant disability and longer follow-up is needed to better determine natural history and evaluate appropriate treatment interventions.

The contemporary spectrum of multiple sclerosis misdiagnosis: A multicenter study

Objective: To characterize patients misdiagnosed with multiple sclerosis (MS). Methods: Neurologists at 4 academic MS centers submitted data on patients determined to have been misdiagnosed with MS. Results: Of 110 misdiagnosed patients, 51 (46%) were classified as “definite” and 59 (54%) “probable” misdiagnoses according to study definitions. Alternate diagnoses included migraine alone or in combination with other diagnoses 24 (22%), fibromyalgia 16 (15%), nonspecific or nonlocalizing neurologic symptoms with abnormal MRI 13 (12%), conversion or psychogenic disorders 12 (11%), and neuromyelitis optica spectrum disorder 7 (6%). Duration of misdiagnosis was 10 years or longer in 36 (33%) and an earlier opportunity to make a correct diagnosis was identified for 79 patients (72%). Seventy-seven (70%) received disease-modifying therapy and 34 (31%) experienced unnecessary morbidity because of misdiagnosis. Four (4%) participated in a research study of an MS therapy. Leading factors contributing to misdiagnosis were consideration of symptoms atypical for demyelinating disease, lack of corroborative objective evidence of a CNS lesion as satisfying criteria for MS attacks, and overreliance on MRI abnormalities in patients with nonspecific neurologic symptoms. Conclusions: 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.

Mind-Body Medicine for Multiple Sclerosis: A Systematic Review

Background. Mind-body therapies are used to manage physical and psychological symptoms in many chronic health conditions. Objective. To assess the published evidence for using mind-body techniques for symptom management of multiple sclerosis. Methods. MEDLINE, PsycINFO, and Cochrane Clinical Trials Register were searched from inception to March 24, 2012. Eleven mind-body studies were reviewed (meditation, yoga, biofeedback, hypnosis, relaxation, and imagery). Results. Four high quality trials (yoga, mindfulness, relaxation, and biofeedback) were found helpful for a variety of MS symptoms. Conclusions. The evidence for mind-body medicine in MS is limited, yet mind-body therapies are relatively safe and may provide a nonpharmacological benefit for MS symptoms.

Body-worn sensors capture variability, but not decline, of gait and balance measures in multiple sclerosis over 18 months.

Gait and balance deficits are a frequent complaint in MS but poorly captured by stopwatch-timed tests or rating scales. Body-worn accelerometers and gyroscopes are able to detect gait and balance abnormalities in people with MS who have normal walking speeds. Few longitudinal studies exist using this technology to study the evolution of mobility deficits. The purpose of this study was to determine if body-worn sensors detected any decline in gait and balance measures in people with MS over time. Twenty-seven people with MS (13 mildly disabled, self-rated expanded disability status scale 0-3.5; 14 moderately disabled, SR-EDSS 4.0-5.5) who had normal walking speeds and 18 matched control subjects underwent gait and balance testing using body-worn sensors every 6 months for 18 months. While no parameter worsened over time, the moderately disabled MS cohort performed more poorly than the mildly disabled MS cohort who, in turn, was worse than control subjects for both objective and subjective walking and balance measures. Furthermore, the moderately disabled MS cohort demonstrated greater variation in between-visit performance than did the less disabled MS cohort or controls (Bonferroni-corrected p<0.05). Variability may be a key indicator of worsening gait and balance disability in MS.

Postural response latencies are related to balance control during standing and walking in patients with multiple sclerosis

OBJECTIVE To understand and examine the relation between postural response latencies obtained during postural perturbations and representative measures of balance during standing (sway variables) and walking (trunk motion). DESIGN Cross-sectional. SETTING University medical center. PARTICIPANTS Persons with multiple sclerosis (MS) (n=40) were compared with similar aged control subjects (n=20). There were 20 subjects with MS in the normal walking velocity group and 20 subjects with MS who had slow walking velocity based on a timed 25-foot walk (T25FW) of <5 seconds. INTERVENTIONS None. MAIN OUTCOME MEASURES Postural response latency, sway variables, trunk motion variables. RESULTS We found that subjects with MS with both slow or normal walking velocities had significantly longer postural response latencies than the healthy control group. Postural response latency was not correlated with the T25FW. Postural response latency was significantly correlated with center of pressure sway variables during quiet standing (root mean square: ρ=.334, P=.04; range: ρ=.385, P=.017; mean velocity: ρ=.337, P=.038; total sway area: ρ=.393, P=.015). Postural response latency was also significantly correlated with motion of the trunk during walking (sagittal plane range of motion: ρ=.316, P=.05; SD of transverse plane range of motion: ρ=-.43, P=.006). CONCLUSIONS These findings clearly indicate that slow postural responses to external perturbations in patients with MS contribute to disturbances in balance control during both standing and walking.

When metals compete: a case of copper-deficiency myeloneuropathy and anemia.

Background A 47-year-old woman with an otherwise unremarkable medical history was referred to the multiple sclerosis clinic by her primary neurologist for evaluation of a 2–3 year history of progressive knee and back pain, weakness, paresthesias, sensory loss, ataxia, and falls. During the same period, she had received blood transfusions for unexplained anemia and leukopenia. She had been wearing dentures for many years.Investigations Physical examination, neurological examinations (assessments of reflexes, gait, proprioception, and sensitivity to temperature, pinprick and vibration), neurophysiological studies (visual and brainstem somatosensory evoked potentials, nerve conduction studies and electromyography), T2-weighted MRI of the brain and spine, cerebrospinal fluid analysis and serum evaluations.Diagnosis Myeloneuropathy and anemia due to copper deficiency, secondary to zinc overload associated with long-term use of denture cream with a high zinc content.Management Change to a low-zinc denture cream and oral copper replacement.

Recent developments in multiple sclerosis therapeutics.

Multiple sclerosis, the most common neurologic disorder of young adults, is traditionally considered to be an inflammatory, autoimmune, demyelinating disease of the central nervous system. Based on this understanding, the initial therapeutic strategies were directed at immune modulation and inflammation control. These approaches, including high-dose corticosteroids for acute relapses and long-term use of parenteral interferon-β, glatiramer acetate or natalizumab for disease modification, are at best moderately effective. Growing evidence supports that, while an inflammatory pathology characterizes the early relapsing stage of multiple sclerosis, neurodegenerative pathology dominates the later progressive stage of the disease. Multiple sclerosis disease-modifying therapies currently in development attempt to specifically target the underlying pathology at each stage of the disease, while avoiding frequent self-injection. These include a variety of oral medications and monoclonal antibodies to reduce inflammation in relapsing multiple sclerosis and agents intended to promote neuroprotection and neurorepair in progressive multiple sclerosis. Although newer therapies for relapsing MS have the potential to be more effective and easier to administer than current therapies, they also carry greater risks. Effective treatments for progressive multiple sclerosis are still being sought.

A randomized controlled phase II trial of riluzole in early multiple sclerosis

We evaluated the effect of riluzole versus placebo added to weekly IM interferon beta‐1a in early multiple sclerosis (MS).