Split-belt locomotion in Parkinson's disease with and without freezing of gait.

BACKGROUND: Parkinson's disease (PD) patients have an increased gait asymmetry and variability, which is most pronounced in patients with freezing of gait (FOG). We examined if stride time variability and deficits in interlimb coordination between the upper and lower limbs would increase during split-belt locomotion in PD, and particularly so in patients with FOG. METHODS: Fourteen PD patients (seven with FOG, matched for disease severity with the seven non-freezers) and 10 healthy controls walked on a treadmill with split belts at different speeds (2 versus 3km/h). Gait was recorded by means of a video motion analysis system. Outcome measures were stride length asymmetry and variability, stride time asymmetry and variability, ipsilateral and contralateral interlimb coordination, and phase coordination index. RESULTS: Both PD subjects and controls were able to adapt to split-belt walking by modulating their stride length. However, freezers showed a larger increase in stride time asymmetry and stride time variability due to split-belt walking compared to non-freezers. Furthermore, contralateral interlimb coordination improved in control subjects during split-belt walking, but not in PD patients (freezers and non-freezers). Phase coordination index did not change differently across the three groups. CONCLUSIONS: The ability to walk under split-belt conditions was preserved in PD. Non-freezers and controls compensated for the experimentally increased stride length asymmetry by decreasing their stride time asymmetry. This ability was lost in freezers, who in fact increased their stride time asymmetry during split-belt walking. As a result, stride time variability also increased in freezers. These findings support the hypothesis that FOG is related to gait asymmetries and to gait timing deficits.

"On" state freezing of gait in Parkinson disease: a paradoxical levodopa-induced complication.

OBJECTIVE: To describe the phenotype of levodopa-induced "on" freezing of gait (FOG) in Parkinson disease (PD). METHODS: We present a diagnostic approach to separate "on" FOG (deterioration during the "on state") from other FOG forms. Four patients with PD with suspected "on" FOG were examined in the "off state" (>12 hours after last medication intake), "on state" (peak effect of usual medication), and "supra-on" state (after intake of at least twice the usual dose). RESULTS: Patients showed clear "on" FOG, which worsened in a dose-dependent fashion from the "on" to the "supra-on" state. Two patients also demonstrated FOG during the "off state," of lesser magnitude than during "on." In addition, levodopa produced motor blocks in hand and feet movements, while other parkinsonian features improved. None of the patients had cognitive impairment or a predating "off" FOG. CONCLUSIONS: True "on" FOG exists as a rare phenotype in PD, unassociated with cognitive impairment or a predating "off" FOG. Distinguishing the different FOG subtypes requires a comprehensive motor assessment in at least 3 medication states.

Walking patterns in Parkinson's disease with and without freezing of gait.

The pathophysiology underlying freezing of gait (FOG) in Parkinson's disease remains incompletely understood. Patients with FOG ("freezers") have a higher temporal variability and asymmetry of strides compared to patients without FOG ("non-freezers"). We aimed to extend this view, by assessing spatial variability and asymmetry of steps and interlimb coordination between the upper and lower limbs during gait. Twelve freezers, 15 non-freezers, and 15 age-matched controls were instructed to walk overground and on a treadmill. Kinematic data were recorded with a motion analysis system. Both freezers and non-freezers showed an increased spatial variability of leg movements compared to controls. In addition, both patient groups had a deficit in interlimb coordination, not only between ipsilateral arms and legs, but also between diagonally positioned limbs. The only difference between freezers and non-freezers was a decreased step length during treadmill walking. We conclude that parkinsonian gait-regardless of FOG-is irregular, not only in the legs, but also with respect to interlimb coordination between the arms and legs. FOG is reflected by abnormal treadmill walking, presumably because this provides a greater challenge to the defective supraspinal control than overground walking, hampering the ability of freezers to increase their stride length when necessary.

Motor imagery of foot dorsiflexion and gait: effects on corticospinal excitability.

OBJECTIVE: We examined how corticospinal excitability was affected by motor imagery of foot dorsiflexion and motor imagery of gait. METHODS: Transcranial magnetic stimulation was applied over the primary motor cortex of 16 young healthy subjects while they performed imaginary foot dorsiflexions (Experiment I) and imaginary walking (Experiment II). Motor-evoked potentials (MEPs) were recorded from the tibialis anterior (TA) and first dorsal interosseus (FDI). MEPs recorded during motor imagery were compared to those recorded during a matched visual imagery task. RESULTS: Imagined foot dorsiflexions increased MEP areas in both TA and FDI. The increase in TA was stronger than in FDI. Overall, imagined walking did not change MEP areas. However, subjects with larger increases in TA during imagined foot dorsiflexion also showed larger increases in TA during imagined walking. CONCLUSIONS: Imagined foot dorsiflexions increase corticospinal excitability in both a task-related muscle (TA) and a task-unrelated muscle (FDI), with larger increases in the task-related muscle. Imagined gait only increases corticospinal excitability in those subjects with the largest increments during imagined foot dorsiflexion. SIGNIFICANCE: Imagery of a simple lower extremity movement evokes increases in corticospinal excitability. Furthermore, corticospinal effects of a simple motor imagery task can predict corticospinal effects of a more complex motor imagery task involving the same muscle.

Assessing the interplay between cognition and gait in the clinical setting.

In this review, we outline how the influence of cognitive processes on gait or balance can be appreciated in a clinical setting. Careful history taking of the patient or direct carer provides information about multiple task problems in daily life and the presence of cognitive impairment, depression or fear of falling. Physical examination may reveal abnormalities such as an inappropriately high walking speed or an inability to handle secondary tasks while walking. Assessment of frontal executive function helps to understand the nature of these multiple task problems and to detect "risky" behaviour caused by frontal disinhibition. Examples of clinically useable techniques include pressure-sensitive insoles or an electronic walkway (to record strides) or accelerometers (to measure body motion while walking). Combining these assessments may lead to a better appreciation of the fascinating but complex interplay between cognition and gait.

[Gait disorders due to neurological conditions]. / Loopstoornissen door neurologische aandoeningen.

Gait disorders are seen frequently and often have a neurological cause. The clinical management of patients presenting with a gait disorder is often complicated due to the large number of diseases that can cause a gait disorder and to the difficulties in interpreting a specific gait disorder properly. In addition, the currently available classification systems are confusing. Gait disorders can be classified into the following categories: antalgic, paretic-hypotonic, spastic, vestibular, ataxic, hypokinetic-rigid, cautious, or functional. A correct interpretation of the gait disorder is important as this determines the diseases to be considered, the auxilliary investigations that have to be carried out, and the selection of rational therapeutic options.

Beck Depression Inventory is a useful screening tool for major depressive disorder in Gilles de la Tourette syndrome.

This study determined the prevalence of and factors associated with comorbid major depressive disorder (MDD) in patients with Gilles de la Tourette syndrome (GTS). How a simple self-report instrument, the Beck Depression Inventory (BDI), correlates with clinical assessment of comorbid MDD in this population was assessed. In a continuous sample of 114 adult patients with GTS, assessed clinically using the Diagnostic and Statistical Manual of Mental Disorders-IV criteria, 26 (23%) patients met criteria for MDD; more severe tics as measured with the Yale Global Tic Severity Scale, conduct disorder in childhood or higher age at the time of assessment were associated with MDD. The BDI score had a high negative predictive value for diagnosis of MDD, but a low positive predictive value. Using the BDI as a screening tool for comorbid MDD in patients with GTS is suggested.

Subthreshold rTMS over pre-motor cortex has no effect on tics in patients with Gilles de la Tourette syndrome.

OBJECTIVE: A previous study showed no effect of 1Hz repetitive transcranial magnetic stimulation (rTMS) on tics in Gilles de la Tourette Syndrome (GTS). We modified the rTMS protocol in order to investigate some of the possible methodological reasons for the negative outcome in that study. METHODS: In a single blinded placebo-controlled cross-over study in five GTS patients without obsessive compulsive disorder we probed whether longer trains (1800 stimuli) of 1 Hz pre-motor cortex rTMS at 80% of active motor threshold and application to both hemispheres can improve tics in GTS. This was measured with the Yale Global Tic severity rating scale, the MOVES self-rating scale and video analysis. RESULTS: We found no significant effect of either left pre-motor cortex stimulation alone, or left pre-motor followed by right pre-motor cortex stimulation. CONCLUSIONS: These results suggest that the rTMS protocol used in this study is not useful for the treatment of tics in GTS. SIGNIFICANCE: rTMS protocols need to be modified substantially in order to explore their potential for the treatment of tics in GTS.

[Repetitive transcranial magnetic stimulation in depression; stimulation of the brain in order to cure the psyche]. / Repetitieve transcraniële magnetische stimulatie bij depressie; stimulatie van het brein om de psyche te genezen.

Transcranial magnetic stimulation (TMS) is a non-invasive approach to briefly stimulate or inhibit cortical brain areas. A novel approach entails the delivery of repetitive TMS pulses (rTMS) at a fixed frequency. In rTMS cortical activity is altered beyond the period of actual stimulation. The changes occur locally as well as at a distance in functionally connected brain areas. These features render rTMS a suitable tool to study normal brain functions and the pathophysiology of brain diseases. Furthermore, it is expected that rTMS could be used as a novel therapy for neurological or psychiatric diseases characterised by abnormal cortical activation. This possibility has been studied mostly in patients suffering from depression, where rTMS has been used to restore normal activity in the hypoactive prefrontal cortex. Despite statistically significant therapeutic effects in small sized trials, the clinical implications are still limited.

The variability of intracortical inhibition and facilitation.

OBJECTIVE: To assess the variability of transcranial magnetic stimulation paired pulse measurements of cortical excitability between subjects, between sessions and within subjects within sessions. METHODS: In experiment 1, intracortical inhibition and facilitation were assessed with a fixed conditioning stimulus intensity (CSI) of 80% of active motor threshold (AMT) whereas in experiment 2, the effect of different CSIs (60-110% of AMT) was investigated. RESULTS: Experiment 1 revealed that subjects differed significantly in the degree of inhibition and facilitation. Between sessions the variability was substantial as predicted by high within session variability. Experiment 2 allowed determination of individual thresholds for inhibition and facilitation. These thresholds were the best predictor of the amount of inhibition or facilitation at a given CSI. Across subjects we observed a high correlation of the threshold for inhibition (expressed in terms of maximum stimulator output) with AMT (r=0.93). Results for facilitation were more variable. CONCLUSIONS: The variability was high if a single CSI was used to compare the percent intracortical inhibition or facilitation between subjects, or between sessions. Much less variable was the threshold for intracortical inhibition/facilitation, which was highly correlated to AMT. We suggest that the ratio of CSI:AMT is a robust and useful additional measure of the integrity of neuronal circuits underlying intracortical inhibition/facilitation.