Parkinsonism is a Phenotypical Signature of Amyloidopathy in Patients with Gait Disorders.

BACKGROUND: Central neurological gait abnormalities (CNGA) are frequently associated with parkinsonism in older adults. However, the neuropathological substrates and the clinical impact of parkinsonism have been not described in CNGA. OBJECTIVE: This cross-sectional study aims to compare the CSF total tau, Aß1-42, and phosphorylated tau levels in non-Parkinson's disease (PD) patients with CNGA with and without parkinsonism and to study the clinical impact of parkinsonism on gait and cognition. METHODS: CSF biomarkers were measured by ELISA in 49 non-PD patients with CNGA (77.7±6.6 years; 32.7% women). Gait was quantified with an optoelectronic system and cognition with a comprehensive neuropsychological assessment. Parkinsonism was defined by presence of bradykinesia and at least one of the following signs among muscular rigidity, rest tremor, or postural instability. RESULTS: Parkinsonism was identified in 14 CNGA patients (28.6% ). CSF Aß1-42 level was decreased in CNGA patients with parkinsonism (ß: - 189.4; 95% CI [- 352.3; - 26.6]; p = 0.024) even after adjusting for age, gender, comorbidities, and total white matter burden; while CSF total tau and phosphorylated tau levels were similar between CNGA patients with and without parkinsonism. CNGA patients with parkinsonism presented decreased attentional and executive performances but similar gait parameters than those without parkinsonism. CONCLUSION: Parkinsonism represents a phenotype related with amyloidopathy-decreased CSF Aß1-42 level-in non-PD patients with CNGA. This phenotype is clinically associated with impaired cognition, but similar quantitative gait parameters in comparison to CNGA patients without parkinsonism.

Apathy in idiopathic normal pressure hydrocephalus: A marker of reversible gait disorders.

OBJECTIVE: Apathy-the most common behavioral disturbance in idiopathic normal pressure hydrocephalus (iNPH)-is associated with poor gait, but the role of apathy on gait improvement after cerebrospinal fluid (CSF) tapping has not been studied yet. This study aims to compare gait improvement after CSF tapping in iNPH patients with and without apathy. METHODS: Stride time variability (STV), a marker of higher level of gait control, was measured in 33 iNPH patients (78.4 ± 5.7 years; 36.4% women) with an optoelectronic system during usual walking (single task) and during walking while dual tasking of counting and verbal fluency before and 24 hours after CSF tapping. Apathy was defined by a score ≥14 on the Starkstein apathy scale. RESULTS: Apathy was present in 60.6% of patients. Cerebrospinal fluid tapping led to greater improvement of STV (ie, decrease) during dual-task walking (and more specifically categorical verbal fluency) in apathetic compared to nonapathetic patients (-44.7 ± 58.1% versus +4.24 ± 67.6%, respectively; P = .040), even after adjusting for age and depressive symptoms. More severe apathy was correlated with better STV improvement while dual tasking (categorical verbal fluency) after CSF tapping (r = -0.412; P-value = 0.021), while it was not correlated with improvement on executive tests. CONCLUSIONS: Our findings suggest that the presence of apathy is a predictor of better outcomes of gait disorders after CSF tapping in patients with iNPH.

Does fear of falling predict gait variability in multiple sclerosis?

BACKGROUND: Behavioural symptoms and gait disorders are very common in patients with multiple sclerosis. OBJECTIVE: To evaluate the association between fear of falling and gait instability at one year in patients with multiple sclerosis. METHODS: Thirty-five multiple sclerosis patients were included. Fear of falling was assessed by the Fall Efficacy Scale-International and gait variability with stride time variability under single and dual-task conditions at baseline and at one year. RESULTS: Baseline fear of falling score was associated with increased stride time variability at one year during dual-task condition even after adjustment on covariates. CONCLUSION: Fear of falling is associated with gait variability at one year, especially under dual-task condition.

CSF tapping also improves mental imagery of gait in normal pressure hydrocephalus.

This study aims to compare the changes of Timed Up and Go (TUG) and its imagined version (iTUG) after CSF tapping between patients with idiopathic normal pressure hydrocephalus (iNPH) and its mimics. TUG and iTUG were performed before and 24 h after CSF tapping in 117 patients (75.8 ± 6.9 years; 35% female) with suspicion of iNPH (68 iNPH and 49 mimics). Mental imagery of locomotion was modified after CSF tapping in iNPH patients, but not in the mimics.

Upper limb movement analysis during gait in multiple sclerosis patients.

PURPOSE: Gait disorders in multiple sclerosis (MS) are well studied; however, no previous study has described upper limb movements during gait. However, upper limb movements have an important role during locomotion and can be altered in MS patients due to direct MS lesions or mechanisms of compensation. The aim of this study was to describe the arm movements during gait in a population of MS patients with low disability compared with a healthy control group. METHODS: In this observational study we analyzed the arm movements during gait in 52 outpatients (mean age: 39.7±9.6years, female: 40%) with relapsing-remitting MS with low disability (mean EDSS: 2±1) and 25 healthy age-matched controls using a 3-dimension gait analysis. RESULTS: MS patients walked slower, with increased mean elbow flexion and decreased amplitude of elbow flexion (ROM) compared to the control group, whereas shoulder and hand movements were similar to controls. These differences were not explained by age or disability. CONCLUSION: Upper limb alterations in movement during gait in MS patients with low disability can be characterized by an increase in mean elbow flexion and a decrease in amplitude (ROM) for elbow flexion/extension. This upper limb movement pattern should be considered as a new component of gait disorders in MS and may reflect subtle motor deficits or the use of compensatory mechanisms.

A combined cognitive and gait quantification to identify normal pressure hydrocephalus from its mimics: The Geneva's protocol.

OBJECTIVES: Idiopathic normal pressure hydrocephalus (iNPH) is very prevalent in aging, underdiagnosed, and represents a rare cause of reversible neurological condition. The clinical triad of iNPH - gait, cognitive and urinary symptoms - and its neuroradiological features (i.e. ventriculomegaly) are not specific and found a various neurodegenerative and/or vascular conditions. We present our iNPH standardized protocol at the Geneva University Hospitals involving a multispecialty team of behavioral neurologists, neurosurgeons, neuropsychologists, engineers, and physical therapists. Based on a pragmatic approach, the goal of this protocol is to improve the identification of older patients with iNPH from its mimics (i.e. vascular dementia or other parkinsonian syndromes). PATIENTS AND METHODS: We used a novel standardized paradigm with a simultaneous quantification of cognition and gait (dual task gait assessment and mental imagery of locomotion) before and 24h after CSF tapping. RESULTS: We assessed 125 patients with suspicion of iNPH (age: 75.9±7.4years; 34.4% female) in 5 years: 54.4% of probable/possible iNPH and 45.6% of mimics. Among the mimics, vascular dementia (24.6%) and patients with multifactorial conditions (19.9%) were the two most common diagnoses. A total of 27 patients with iNPH (39.7%) accepted the neurosurgical shunt procedure. CONCLUSION: This report shows that a quantified gait and cognitive assessment - using dual-task paradigms - before and after CSF tapping is feasible among older adults with suspicion of iNPH and that this multidisciplinary approach contributes to the identification of patients with iNPH from its mimics.

Apathy and higher level of gait control in normal pressure hydrocephalus.

Apathy represents the most common behavioral disturbance in patients with suspicion of idiopathic normal pressure hydrocephalus (iNPH) and has a major impact on quality of life. However, its impact on gait -the hallmark motor disturbance of iNPH - has never been studied yet. This study aims to evaluate the impact of apathy on higher level of gait control in patients with suspicion of iNPH. Stride time variability (STV), a marker of higher level of gait control, was quantified during usual walking (single task) and during walking while performing simultaneously cognitive tasks (dual task) of counting and verbal fluency. Among 46 patients with suspicion of iNPH (77.6±6.7years; 34.8% women), 30 (65.2%) presented apathy (defined by a score≥14 on the Starkstein apathy scale). Backward counting induced more important worsening of STV (i.e. increasing STV) in apathetic compared to non-apathetic patients (14.8±25.1% versus 9.0±20.4%; p=0.005), while both groups presented similar executive functioning. These findings suggest that apathy contributes to gait disorders in iNPH. Apathy is easy to monitor and should be considered as a target symptom of treatment.

Gait Profile Score in multiple sclerosis patients with low disability.

BACKGROUND: Gait abnormalities are subtle in multiple sclerosis (MS) patients with low disability and need to be better determined. As a biomechanical approach, the Gait Profile Score (GPS) is used to assess gait quality by combining nine gait kinematic variables in one single value. This study aims i) to establish if the GPS can detect gait impairments and ii) to compare GPS with discrete spatiotemporal and kinematic parameters in low-disabled MS patients. METHOD: Thirty-four relapsing-remitting MS patients with an Expanded Disability Status Scale (EDSS) score ≤2 (mean age 36.32±8.72 years; 12 men, 22 women; mean EDSS 1.19±0.8) and twenty-two healthy controls (mean age 36.85±7.87 years; 6 men, 16 women) matched for age, weight, height, body mass index and gender underwent an instrumented gait analysis. RESULTS: No significant difference in GPS values and in spatiotemporal parameters was found between patients and controls. However patients showed a significant alteration at the ankle and pelvis level. CONCLUSION: GPS fails to identify gait abnormalities in low-disabled MS patients, although kinematic analysis revealed subtle gait alterations. Future studies should investigate other methods to assess gait impairments with a gait score in low-disabled MS patients.

Stride time variability as a marker for higher level of gait control in multiple sclerosis: its association with fear of falling.

Fear of falling (FOF) and gait disorders represent both prevalent symptoms in patients with multiple sclerosis (MS); however, the association between FOF and higher level of gait control (HLGC) has not been studied in MS. This study aims to assess the association between FOF and HLGC in patients with MS. HLGC was assessed by stride time variability (STV) during single and dual-tasks (forward counting, backward counting, categorical verbal fluency and literal verbal fluency) and FOF was quantified by the falls efficacy scale-international (FES-I). Seventy-one patients (age: 39.27 ± 9.77 years; 63 % female) were included in this cross-sectional study (Expanded Disability Status Scale (median): 2.00) with a low prevalence of FOF (FES-I: 21.52 ± 8.37). The mean gait speed was 1.19 ± 0.23 m/s with a STV of 2.35 ± 1.68 % during single walking task. STV during single task and the dual tasks of forward counting and backward counting were associated with the FES-I in the univariable linear regression models (p ≤ 0.001), but only STV while backward counting (ß: 0.42, [0.18;0.66]) was associated with FOF in the multivariable model (adjusted for age, gender, previous fall, Expanded Disability Status Scale and gait speed). These findings indicate that FOF is associated with STV while backward counting, a marker of HLGC in relationship with working memory in a MS population including a majority of low disabled patients.

Gait variability in multiple sclerosis: a better falls predictor than EDSS in patients with low disability.

This longitudinal study aims to compare the role of stride time variability (STV) and EDSS for predicting falls in 50 patients with multiple sclerosis with low disability. 21.7 % developed falls (follow-up: 22 months). STV (IRR: 1.73, 95 % CI: 1.23-2.41, p = 0.001) and EDSS (IRR: 2.29, 95 % CI: 1.35-3.90, p = 0.002) were associated with the number of falls. Adding STV to EDSS improves the predictive power of the model from 21 to 26 %, but not adding EDSS to STV.

Gait and physical impairments in patients with acute ankle sprains who did not receive physical therapy.

OBJECTIVE: To assess ankle function 4 weeks after conservative management and to examine the correlation of function with gait. DESIGN: A prospective comparison study. PATIENTS: Thirty patients with grade I or II acute ankle sprains were followed up after 4 weeks of conservative management not involving physical therapy. METHODS: Participants underwent a clinical assessment and had to walk at a normal self-selected walking speed. Their results were compared with the data of 15 healthy subjects. MAIN OUTCOME MEASURES: Participants' joint swelling, muscle strength, passive mobility, and pain were assessed. In addition, patients' temporal-spatial, kinematic, and kinetic gait data were measured while walking. RESULTS: Muscle strength and passive mobility were significantly reduced on the injured side compared with the noninjured side (P < .001). During gait analysis, patients with ankle sprains showed slower walking speed, shorter step length, shorter single support time, reduced and delayed maximum plantar flexion, decreased maximum power, and decreased maximum moment (P < .050) compared with healthy persons. Decreased walking speed was mainly correlated with pain (R = -0.566, P = .001) and deficits in muscle strength of dorsiflexors (R = 0.506, P = .004). CONCLUSION: Four weeks after an ankle sprain, patients who did not receive physical therapy showed physical impairments of the ankle that were correlated with gait parameters. These findings might help fine-tune rehabilitation protocols.

Dual-task assessment in natalizumab-treated multiple sclerosis patients.

BACKGROUND: To study the 1-year evolution of quantitative dual-task gait parameters in comparison with single-task gait parameters and detailed neuropsychological assessment in patients with multiple sclerosis (MS) treated with natalizumab. METHODS: Walking speed, stride length and stride time during a dual task (walking while forward counting, backward counting, semantic fluency, and phonemic fluency), a single walking task, and a detailed neuropsychological assessment were prospectively measured and assessed twice at the 1-year interval in 9 consecutive patients with MS treated with natalizumab. RESULTS: Dual-task-related gait changes (walking speed, stride length and stride time while performing semantic fluency and walking speed, and stride time while performing phonemic fluency) showed a significant improvement after 1 year of treatment with natalizumab. The single walking task and detailed neuropsychological assessment did not present any modification. CONCLUSIONS: Dual-task-related gait changes using a cognitive task with a specific executive demand represent an interesting marker of disease-modifying therapy in patients with MS.

Dual-task related gait changes after CSF tapping: a new way to identify idiopathic normal pressure hydrocephalus.

BACKGROUND: Gait disturbances found in patients with idiopathic normal pressure hydrocephalus (iNPH) are unspecific to the diagnosis and commonly occur in neurodegenerative or vascular conditions (iNPH-like conditions). This current retrospective pre-post intervention study aims to determine whether changes in quantitative gait parameters during dual task condition differed between iNPH and iNPH-like conditions before and after cerebrospinal fluid (CSF) tapping. METHODS: 49 patients assessed before and after CSF tapping were included in this study (27 with iNPH and 22 with iNPH-like conditions). Gait analysis during single and dual task conditions (walking and backward counting) was performed before and after a CSF spinal tap of 40 ml. Gait parameters were compared between iNPH and iNPH-like conditions patients. Logistic regressions were used to examine the association between iNPH and gait parameters. RESULTS: Improvements of step width (-9.03 (20.75)% for iNPH group; +0.28 (21.76)% for iNPH-like conditions group), stride length (+7.82 (20.71)% for iNPH group; -0.62 (19.22)% for iNPH-like conditions group), walking speed (+12.20 (29.79)% for iNPH group; +2.38 (32.50)% for iNPH-like conditions group) and stance duration (-1.23 (4.03)% for iNPH group; +0.49 (5.12)% for iNPH-like conditions group) during dual task, after CSF spinal tapping, were significant in patients with iNPH compared to patients with iNPH-like conditions. No between group difference was observed for the single walking task evaluation. The multiple logistic regression revealed that among these four gait parameters, only the improvement in step width was associated with the diagnosis of iNPH. CONCLUSION: Dual-task related changes in spatio-temporal gait parameters before and after CSF tapping might be a novel and discriminative method of identifying iNPH patients from other similar conditions.