Verbal Fluencies and Fampridine Treatment in Multiple Sclerosis.

BACKGROUND/AIMS: Fampridine is sometimes reported to improve cognition and especially the information-processing speed. Motor improvement might be a confounding factor. The aim of this study was to evaluate the effects of fampridine on verbal fluencies in patients with multiple sclerosis (MS). METHODS: Fifty MS patients were included in a prospective monocentric open label trial with a mean Expanded Disability Status Scale of 5.3 ± 1.1. Assessments of verbal phonological and semantic fluencies were repeated twice (within 1 week) before fampridine treatment and twice after fampridine treatment in order to have the maximal practice effect. Gait velocity and fatigue (visual analogical scale) were also assessed. Distribution into gait responders, gait non-responders, fluency responders and fluency non-responders, was described. RESULTS: Verbal fluencies were significantly higher after fampridine treatment. No correlation was observed between phonological fluency improvement and semantic fluency improvement. Gait responders and gait non-responders did not present significant differences in verbal fluency performance and fatigue score. No correlation between gait velocity improvement and fatigue improvement compared with verbal fluency improvement was observed. CONCLUSION: Our results suggest that fampridine could have a selective procognitive effect on phonological fluency in MS, even in the gait non-responder patients.

High beta activity in the subthalamic nucleus and freezing of gait in Parkinson's disease.

OBJECTIVE: Oscillatory activity in the beta band is increased in the subthalamic nucleus (STN) of Parkinson's disease (PD) patients. Rigidity and bradykinesia are associated with the low-beta component (13-20Hz) but the neurophysiological correlate of freezing of gait in PD has not been ascertained. METHODS: We evaluated the power and coherence of the low- and high-beta bands in the STN and cortex (EEG) of PD patients with (p-FOG) (n=14) or without freezing of gait (n-FOG) (n=8) in whom electrodes for chronic stimulation in the STN had been implanted for treatment with deep brain stimulation. RESULTS: p-FOG patients showed higher power in the high-beta band (F=11.6, p=0.002) that was significantly reduced after l-dopa administration along with suppression of FOG (F=4.6, p=0.042). High-beta cortico-STN coherence was maximal for midline cortical EEG electrodes, whereas the low-beta band was maximal for lateral electrodes (χ(2)=20.60, p<0.0001). CONCLUSIONS: The association between freezing of gait, high-beta STN oscillations and cortico-STN coherence suggests that this oscillatory activity might interfere in the frontal cortex-basal ganglia networks, thereby participating in the pathophysiology of FOG in PD.

Clinical and single-photon emission computed tomography study of pure akinesia with freezing of gait.

The clinical syndrome of pure akinesia (PA) is considered the third phenotype of progressive supranuclear palsy (PSP), and is characterized by freezing of gait and prominent speech disturbance without rigidity or tremor. It is frequently considered one of the dopamine resistant motor syndromes, and its pathophysiology remains unclear. We report a patient followed in the Department of Neurology of Razi Hospital, Tunisia, with PA with gait freezing (PAGF) with a frontal hypoperfusion on single photon emission CT and non-responsive dopa therapy. We discuss the clinical features of PAGF and efficiency of treatment options.

Bloqueos de la marcha sin respuesta al estímulo dopaminérgico con apomorfina en pacientes parkinsonianos graves / Freezing of gait unresponsive to dopaminergic stimulation in patients with severe Parkinsonism

ntroducción: Los episodios de congelación de la marcha (CDM) normalmente aparecen durante el "off" y en general mejoran con tratamiento dopaminérgico a la par que mejoran otros síntomas parkinsonianos. Pacientes y métodos: Presentamos un grupo de 10 pacientes con enfermedad de Parkinson de larga evolución con episodios de CDM. Todos los pacientes presentaban las complicaciones motrices habituales tras años de enfermedad y tratamiento. En todos los pacientes, el síntoma más incapacitante era la aparición de episodios de CDM (freezing) durante el "on". Los pacientes fueron sometidos a un test agudo de apomorfina por vía subcutánea; se consideró dosis eficaz la que inducía la reducción de al menos un 60% en la escala de motricidad de la UPDRS. Resultados: La UPDRS-III basal fue de 61,3 ± 4,7, que se reducía a 21 ± 4,3 tras la inyección de apomorfina s.c. a una dosis media de 5,5 mg (intervalo, 3-7 mg). Durante el "on" inducido por la inyección s.c. de apomorfina mejoraron los parámetros de la marcha relacionados con la bradicinesia, así como el tapping, también en extremidades inferiores, pero los episodios de CDM no variaron de forma significativa. Conclusiones: Presentamos un grupo de 10 pacientes con enfermedad de Parkinson de larga evolución con episodios de CDM que persistían durante el "on", sin respuesta al estímulo dopaminérgico (AU)

Introduction: Freezing of gait unresponsive to dopaminergic stimulation in patients with severe Parkinsonism. The freezing of gait episodes (FOG) normally appear during the “off” period and generally improve with dopaminergic stimulus, at the same time as improving other Parkinsonian symptoms. Patients and methods: We report a group of 10 patients with severe Parkinson’s disease. All patients suffered motor fluctuations, dyskinesias and episodes of FOG during the “on” and “off” state. The patients received a subcutaneous apomorphine bolus, without other dopaminergic medication; an effective dose of apomorphine was considered as one that induced a reduction of at least a 60% in the UPDRS motor scale. Results: The baseline motor UPDRS was 61.3 ± 4.7, which dropped to 21 ± 4.3 after the apomorphine injection. The mean dose of apomorphine was 5.5 mg (3-7 mg). The bolus of apomorphine improved the parameters of the gait related to bradykinesia and the tapping tests of the limbs, but the episodes of FOG did not vary significantly between the “off” and “on” state. Conclusions: We present a group of 10 patients with freezing of gait episodes that did not improve with treatment and persisted during the “on” period induced by dopaminergic stimulus with apomorphine (AU)

Gait apraxia in multiple sclerosis.

BACKGROUND: Gait apraxia is a gait disorder not attributable to motor, cerebellar, or sensory dysfunction. Gait impairment is common in Multiple Sclerosis (MS), but is mostly attributed to spasticity and ataxia. Impairment ratings scales are designed accordingly and do not separately evaluate apraxia. OBJECTIVE: To describe 15 patients with gait apraxia resulting from MS as their major functional impairment. METHODS: The Mayo Clinic database (1994-2007) was searched for the terms MS and gait apraxia. INCLUSION CRITERIA: Definite MS, significant gait apraxia. EXCLUSION CRITERIA: alternative disorder causing apraxia, predominantly spastic/ataxic gait disorder. RESULTS: 9 (60%) of the patients were women, and 12 (80%) had a progressive MS course. Gait apraxia was evident at a median of 8 years (range 0-34) following MS onset. Median EDSS at recognition of gait apraxia was 6.5 (range 5-8). Cognitive dysfunction was present in 11 (73%) and neurogenic bladder dysfunction in 14 (93%). The commonest MRI findings were confluent periventricular T2 lesions, T1 hypointensity and generalized cerebral atrophy with symmetrical ex vacuo ventricular enlargement. CONCLUSION: Gait apraxia can cause significant functional impairment in MS patients, and may be underrecognized. The natural course of the neurological deficit in such patients is unknown, and may differ from that of MS patients with other ambulatory disabilities.

Characterizing gait, locomotor status, and disease severity in children and adolescents with Friedreich ataxia.

BACKGROUND AND PURPOSE: The purpose of this study was to describe gait parameters in children and adolescents with a diagnosis of Friedreich ataxia (FA) and examine the relationship between disease severity, measured by the Friedreich Ataxia Rating Scale (FARS) and gait parameters. The study examined whether FARS scores can discriminate between those who walk independently and those who require assistance. METHODS: Thirty-eight children (aged 5-11 years) and adolescents (aged 12-17 years) with genetically confirmed FA were divided into two groups based on locomotor status: group 1, subjects who were able to walk independently, and group 2, subjects who required assistance for walking. Temporal and spatial gait parameters were collected using the Stride Analyzer computerized foot switch system and compared with age-matched normative data. The FARS was used to measure disease severity. Correlation coefficients and the Mann-Whitney U test of differences were used to evaluate associations and discern differences between groups. RESULTS: In subjects with FA, gait parameters of velocity and cadence were slower and stride length was shorter compared with age-matched children without disabilities. These parameters were significantly correlated with FARS score (r = 0.696, 0.667, 0.537; respectively, all P values <0.001). Total FARS scores were correlated with locomotor status (ç value r = 0.623; P < 0.01) and could categorize subjects into groups based on independent walking or need for assistance, 73% and 87% of the time, respectively. DISCUSSION AND CONCLUSION: Subjects with FA exhibited specific abnormal gait characteristics relative to age-matched individuals. Disease severity, as measured by the FARS, was associated with gait velocity, stride length, and cadence. FARS scores can be used to categorize subjects by locomotor status and may be a useful screening tool to identify those requiring assistance.

The sequence effect and gait festination in Parkinson disease: contributors to freezing of gait?

Festination and freezing of gait (FOG) are poorly understood gait disorders that cause disability and falls in people with Parkinson disease (PD). In PD, basal ganglia malfunction leads to motor set deficits (hypokinesia), while altered motor cue production leads to a sequence effect, whereby movements becomes progressively smaller as in festination. We suggest both factors may contribute to FOG. Disturbance of set maintenance by the basal ganglia in PD has previously been examined in gait, but limited systematic evaluation of the sequence effect exists. In this study, we investigated the step-to-step amplitude relationship in 10 PD subjects with clinical evidence of festination and FOG. Four conditions were examined: off levodopa, off with attentional strategies, off with visual cues, and on levodopa. Participants demonstrated a sequence effect (F = 6.24; P = 0.001), which was reversed only by use of visual cues. In contrast, medication, attentional strategies, and visual cues all improved hypokinesia. Variability was marked both within and between participants in all conditions. The variability of FOG is suggested to relate to a combination of factors, including the sequence effect and its variability, as well as the severity of hypokinesia and its response to medications.