John H. Pula

Mobility, Balance and Falls in Persons with Multiple Sclerosis

Background There is a lack of information concerning the relation between objective measures of gait and balance and fall history in persons with MS (PwMS). This investigation assessed the relation between demographic, clinical, mobility and balance metrics and falls history in persons with multiple sclerosis (MS). Methods 52 ambulatory persons with MS (PwMS) participated in the investigation. All persons provided demographic information including fall history over the last 12 months. Disease status was assessed with Expanded Disability Status Scale (EDSS). Walking speed, coordination, endurance and postural control were quantified with a multidimensional mobility battery. Results Over 51% of the participants fell in the previous year with 79% of these people being suffering recurrent falls. Overall, fallers were older, had a greater prevalence of assistive devices use, worse disability, decreased walking endurance, and greater postural sway velocity with eyes closed compared to non-fallers. Additionally, fallers had greater impairment in cerebellar, sensory, pyramidal, and bladder/bowel subscales of the EDSS. Conclusions The current observations suggest that PwMS who are older, more disabled, utilize an assistive device, have decreased walking coordination and endurance and have diminished balance have fallen in the previous year. This suggests that individuals who meet these criteria need to be carefully monitored for future falls. Future research is needed to determine a prospective model of falls specific to PwMS. Additionally, the utility of interventions aimed at reducing falls and fall risk in PwMS needs to be established.

Quantitative video-oculography to help diagnose stroke in acute vertigo and dizziness: Toward an ECG for the eyes

Background and Purpose— Strokes can be distinguished from benign peripheral causes of acute vestibular syndrome using bedside oculomotor tests (head impulse test, nystagmus, test-of-skew). Using head impulse test, nystagmus, test-of-skew is more sensitive and less costly than early magnetic resonance imaging for stroke diagnosis in acute vestibular syndrome but requires expertise not routinely available in emergency departments. We sought to begin standardizing the head impulse test, nystagmus, test-of-skew diagnostic approach for eventual emergency department use through the novel application of a portable video-oculography device measuring vestibular physiology in real time. This approach is conceptually similar to ECG to diagnose acute cardiac ischemia. Methods— Proof-of-concept study (August 2011 to June 2012). We recruited adult emergency department patients with acute vestibular syndrome defined as new, persistent vertigo/dizziness, nystagmus, and (1) nausea/vomiting, (2) head motion intolerance, or (3) new gait unsteadiness. We recorded eye movements, including quantitative horizontal head impulse testing of vestibulo-ocular-reflex function. Two masked vestibular experts rated vestibular findings, which were compared with final radiographic gold-standard diagnoses. Masked neuroimaging raters determined stroke or no stroke using magnetic resonance imaging of the brain with diffusion-weighted imaging obtained 48 hours to 7 days after symptom onset. Results— We enrolled 12 consecutive patients who underwent confirmatory magnetic resonance imaging. Mean age was 61 years (range 30–73), and 10 were men. Expert-rated video-oculography–based head impulse test, nystagmus, test-of-skew examination was 100% accurate (6 strokes, 6 peripheral vestibular). Conclusions— Device-based physiological diagnosis of vertebrobasilar stroke in acute vestibular syndrome should soon be possible. If confirmed in a larger sample, this bedside eye ECG approach could eventually help fulfill a critical need for timely, accurate, efficient diagnosis in emergency department patients with vertigo or dizziness who are at high risk for stroke.

Small strokes causing severe vertigo Frequency of false-negative MRIs and nonlacunar mechanisms

Objective: Describe characteristics of small strokes causing acute vestibular syndrome (AVS). Methods: Ambispective cross-sectional study of patients with AVS (acute vertigo or dizziness, nystagmus, nausea/vomiting, head-motion intolerance, unsteady gait) with at least one stroke risk factor from 1999 to 2011 at a single stroke referral center. Patients underwent nonquantitative HINTS “plus” examination (head impulse, nystagmus, test-of-skew plus hearing), neuroimaging to confirm diagnoses (97% by MRI), and repeat MRI in those with initially normal imaging but clinical signs of a central lesion. We identified patients with diffusion-weighted imaging (DWI) strokes ≤10 mm in axial diameter. Results: Of 190 high-risk AVS presentations (105 strokes), we found small strokes in 15 patients (median age 64 years, range 41–85). The most common vestibular structure infarcted was the inferior cerebellar peduncle (73%); the most common stroke location was the lateral medulla (60%). Focal neurologic signs were present in only 27%. The HINTS “plus” battery identified small strokes with greater sensitivity than early MRI-DWI (100% vs 47%, p < 0.001). False-negative initial MRIs (6–48 hours) were more common with small strokes than large strokes (53% [n = 8/15] vs 7.8% [n = 7/90], p < 0.001). Nonlacunar stroke mechanisms were responsible in 47%, including 6 vertebral artery occlusions or dissections. Conclusions: Small strokes affecting central vestibular projections can present with isolated AVS. The HINTS “plus” hearing battery identifies these patients with greater accuracy than early MRI-DWI, which is falsely negative in half, up to 48 hours after onset. We found nonlacunar mechanisms in half, suggesting greater risk than might otherwise be assumed for patients with such small infarctions.

Clinically meaningful performance benchmarks in MS Timed 25-Foot Walk and the real world

Objective: Identify and validate clinically meaningful Timed 25-Foot Walk (T25FW) performance benchmarks in individuals living with multiple sclerosis (MS). Methods: Cross-sectional study of 159 MS patients first identified candidate T25FW benchmarks. To characterize the clinical meaningfulness of T25FW benchmarks, we ascertained their relationships to real-life anchors, functional independence, and physiologic measurements of gait and disease progression. Candidate T25FW benchmarks were then prospectively validated in 95 subjects using 13 measures of ambulation and cognition, patient-reported outcomes, and optical coherence tomography. Results: T25FW of 6 to 7.99 seconds was associated with a change in occupation due to MS, occupational disability, walking with a cane, and needing “some help” with instrumental activities of daily living; T25FW ≥8 seconds was associated with collecting Supplemental Security Income and government health care, walking with a walker, and inability to do instrumental activities of daily living. During prospective benchmark validation, we trichotomized data by T25FW benchmarks (<6 seconds, 6–7.99 seconds, and ≥8 seconds) and found group main effects on 12 of 13 objective and subjective measures (p < 0.05). Conclusions: Using a cross-sectional design, we identified 2 clinically meaningful T25FW benchmarks of ≥6 seconds (6–7.99) and ≥8 seconds. Longitudinal and larger studies are needed to confirm the clinical utility and relevance of these proposed T25FW benchmarks and to parse out whether there are additional benchmarks in the lower (<6 seconds) and higher (>10 seconds) ranges of performance.

Posterior reversible encephalopathy syndrome

Purpose of review The ophthalmologist may be called upon to evaluate visual loss in a patient with posterior reversible encephalopathy syndrome. Familiarity with presentation and clinical management is imperative, as visual loss is often reversible with prompt treatment directed at causative factors. Recent findings Since its initial description in 1996, the predisposing factors, clinical presentation and radiographic variation of posterior reversible encephalopathy syndrome continue to expand. Case reports of newly uncovered associations of the syndrome appear frequently. Originally considered a subcortical disease of the posterior cerebrum, posterior reversible encephalopathy syndrome has been shown to affect gray matter and can involve both the anterior and posterior cortex, brainstem, cerebellum or even the spinal cord. The pathophysiologic basis of cerebral edema and molecular mechanisms of edema underlying the syndrome are currently being revealed. Summary Acute hypertension, eclampsia, immunosuppressive medication, infection or autoimmune diseases can all result in the clinical syndrome of vasogenic edema in the central nervous system leading to headache, seizure, confusion and frequent visual loss. The biologic basis for the syndrome is likely an insult to cerebral vascular autoregulation. MRI is essential in diagnosing a cerebral cause for visual loss. The ophthalmologist may have the initial opportunity to diagnose the syndrome. Treatment may reverse clinical deficits, and is based on eliminating the etiologic causation.

Walking and Thinking in Persons With Multiple Sclerosis Who Vary in Disability

OBJECTIVE To examine the effect of a cognitive task on spatiotemporal parameters of gait in persons with multiple sclerosis (MS) with varying disability. DESIGN Cohort. SETTING Testing occurred at a local hospital. PARTICIPANTS Community-living persons (N=78) with MS participated in this investigation. They were divided into 3 groups based on Expanded Disability Status Scale (EDSS) scores: mild (2.0-3.5 EDSS; n=21); moderate (4.0-5.5 EDSS; n=25); and severe (6.0-6.5 EDSS; n=32). INTERVENTIONS Not applicable. MAIN OUTCOME MEASURES Participants walked at a self-selected pace on an electronic pathway, which recorded spatiotemporal parameters of gait, in 4 separate trials and completed a cognitive task in the last 2 trials. The effect of the cognitive task was quantified as the change in spatiotemporal parameters of gait. RESULTS There was an overall decline in gait with the additive cognitive task. The magnitude of the adverse changes ranged from 1.8% for step length (P=.02) to 12% for gait velocity (P<.001). Moreover, adverse changes in gait function were greatest in the severe and moderate disability group (P<.05). CONCLUSIONS Persons with MS have impaired walking while doing a cognitive task, and the adverse effect of a cognitive task on walking function is greatest in persons with severe and moderate disability. Difficulty walking while thinking has implications for everyday life and may be related to the risk of falls. Further work is needed to determine whether the adverse effect of an additive cognitive task can be minimized with rehabilitative interventions.

Accelerometry as a measure of walking behavior in multiple sclerosis

Accelerometry has been identified as a possible ecologically valid and objective approach for measuring community ambulation in multiple sclerosis (MS). This study provides a validation of accelerometer output based on associations with Expanded Disability Status Scale (EDSS), Patient Determined Disease Steps (PDDS) Scale, and Multiple Sclerosis Walking Scale‐12 (MSWS‐12) scores, timed 25‐foot walk (T25FW) and 6‐min walk (6MW) performance, oxygen cost (O2 cost) of walking, and spatial and temporal parameters of gait.

Postural control in multiple sclerosis: Effects of disability status and dual task

Persons with Multiple Sclerosis (PwMS) have postural control impairments. The simultaneous performance of a cognitive task while maintaining an upright posture (i.e. dual task) negatively influences postural control in PwMS with mild disability. This investigation compares the effect of simultaneous cognitive task performance on postural control in PwMS with mild and moderate disability. Forty-five PwMS were divided into groups based on Expanded Disability Status Scale (EDSS) scores: mild (EDSS: 2.0-3.5) and moderate (EDSS: 4.0-6.5) disbaility. Each participant underwent posturography testing during a quiet baseline condition and a cognitive task condition (i.e. dual task). The cognitive task was a word list generation (WLG) task. Median sway velocity, root mean square displacement, and sway area were calculated for each condition. The moderate disability group had significantly worse postural control than the mild disability group. There was an increase in postural sway in the dual task condition. There were no significant task-by-group interactions on postural control. Postural control declines with disability status and is negatively affected by a concurrent cognitive task in PwMS. The dual task cost during a balance task is not different between disability levels and this conflicts with findings for the effect of dual tasking during walking in PwMS.

Further validation of multiple sclerosis walking scale-12 scores based on spatiotemporal gait parameters.

OBJECTIVE To examine the association between Multiple Sclerosis Walking Scale-12 (MSWS-12) scores and spatiotemporal parameters of gait as indicators of gait quality among ambulatory persons with multiple sclerosis (MS). DESIGN Cross-sectional study. SETTING University research laboratory. PARTICIPANTS Community-residing persons with MS (N=268). INTERVENTION Not applicable. MAIN OUTCOME MEASURES Main outcome measures included the MSWS-12 and spatial and temporal gait parameters (walking speed, cadence, step length, step time, base of support [ie, the distance between 1 footfall and the line of progression of the opposing foot], and percentage of gait cycle spent in double support). Secondary outcomes included the timed 25-foot walk (T25FW), 6-minute walk (6MW), and Patient-Determined Disease Steps scale. RESULTS MSWS-12 scores were significantly correlated with walking speed (r=-.59), cadence (r=-.50), step length (r=-.53), step time (r=.46), base of support (r=.29), and percentage of the gait cycle spent in double support (r=.54). MSWS-12 scores further were significantly correlated with T25FW (r=.57) and 6MW (r=-.75) scores. CONCLUSIONS Such findings suggest that the MSWS-12 captures aspects of walking quality, assessed as spatiotemporal parameters of gait, in addition to walking speed and endurance in persons with MS.

Gait variability and disability in multiple sclerosis

Gait variability is clinically relevant in some populations, but there is limited documentation of gait variability in persons with multiple sclerosis (MS). This investigation examined average and variability of spatiotemporal gait parameters in persons with MS and healthy controls and subsequent associations with disability status. 88 individuals with MS (age 52.4±11.1) and 20 healthy controls (age 50.9±8.7) performed two self-paced walking trials on a 7.9-m electronic walkway to determine gait parameters. Disability was indexed by the Expanded Disability Status Scale (EDSS) and ranged between 2.5 and 6.5. Gait variability was indexed by standard deviation (SD) and coefficient of variation (CV=SD/mean) of step time, step length, and step width. Average gait parameters were significantly correlated with EDSS (ρ=0.756-0.609) and were significantly different in individuals with MS compared to controls (p≤0.002). Also, step length (p<0.001) and step time (p<0.001) variability were both significantly greater in MS compared to controls. EDSS was positively correlated with step length variability and individuals with MS who used assistive devices to walk had significantly greater step length variability than those who walked independently (ps<.05). EDSS was correlated with step time and length variability even when age was taken into account. Additionally, Fishers z test of partial correlations revealed that average gait parameters were more closely related to disability status than gait variability in individuals with MS. This suggests that focusing on average gait parameters may be more important than variability in therapeutic interventions in MS.