High-level gait and balance disorders in the elderly: a midbrain disease?

The pathophysiology of gait and balance disorders in elderly people with 'higher level gait disorders' (HLGD) is poorly understood. In this study, we aimed to identify the brain networks involved in this disorder. Standardised clinical scores, biomechanical parameters of gait initiation and brain imaging data, including deep white matter lesions (DWML) and brain voxel-based morphometry analyses, were assessed in 20 HLGD patients in comparison to 20 age-matched controls. In comparison to controls, HLGD patients presented a near-normal preparatory phase of gait initiation, but a severe alteration of both locomotor and postural parameters of first-step execution, which was related to 'axial' hypokinetic-rigid signs. HLGD patients showed a significant grey matter reduction in the mesencephalic locomotor region (MLR) and the left primary motor cortex. This midbrain atrophy was related to the severity of clinical and neurophysiologically determined balance deficits. HLGD patients also showed a reduction in speed of gait, related to 'appendicular' hypokinetic-rigid signs and frontal-lobe-like cognitive deficits. These last two symptoms were correlated with the severity of DWML, found in 12/20 HLGD patients. In conclusion, these data suggest that the gait and balance deficits in HLGD mainly result from the lesion or dysfunction of the network linking the primary motor cortex and the MLR, brain regions known to be involved in the control of gait and balance, whereas cognitive and 'appendicular' hypokinetic-rigid signs mainly result from DWML that could be responsible for a dysfunction of the frontal cortico-basal ganglia loops.

Gait and balance disorders in Parkinson's disease: impaired active braking of the fall of centre of gravity.

Gait and balance disorders are common in Parkinson's disease (PD), but its pathophysiology is still poorly understood. Step length, antero-posterior, and vertical velocities of the center of gravity (CG) during gait initiation were analyzed in 32 controls and 32 PD patients, with and without levodopa, using a force platform. Brain volumes and mesencephalic surface area were measured in PD patients. During the swing limb period, controls showed a fall in the CG, which was reversed before foot-contact indicating active braking of the CG fall. In PD patients, without levodopa, step length and velocity were significantly reduced and no braking occurred before foot-contact in 22 patients. With levodopa, step length and velocity increased in all patients and 7 patients improved their braking capacity. PD patients with normal braking (n = 17) had significantly lower gait and balance disorder scores and higher normalized-mesencephalic surface areas compared to patients with impaired braking (n = 15). The decreased step length and velocity, characteristic of PD, mainly result from degeneration of central dopaminergic systems. The markedly decreased braking capacity observed in half the PD patients contributes to their gait disorders and postural instability, perhaps as a result of nondopaminergic lesions, possibly at the mesencephalic level.

Phasic activation of substantia nigra and the ventral tegmental area by chemical stimulation of the superior colliculus: an electrophysiological investigation in the rat.

The source of short-latency visual input to midbrain dopaminergic (DA) neurons is not currently known; however, the superior colliculus (SC) is a subcortical visual structure which has response latencies consistently shorter than those recorded for DA neurons in substantia nigra and the ventral tegmental area. To test whether the SC represents a plausible route by which visual information may gain short latency access to the ventral midbrain, the present study examined whether experimental stimulation of the SC can influence the activity of midbrain DA neurons. In urethane-anaesthetized rats, 63 pairs of extracellular recordings were obtained from neurons in the SC and ipsilateral ventral midbrain, before and after local disinhibitory injections of the GABA antagonist bicuculline (20-40 ng/200-400 nL saline) into the SC. Neurons recorded from substantia nigra and the ventral tegmental area were classified as putative DA (25/63, 39.7%) or putative non-DA (38/63, 60.3%). In nearly half the cases (27/63, 42.8%), chemical stimulation of the SC evoked a corresponding increase in neural activity in the ventral midbrain. This excitatory effect did not distinguish between DA and non-DA neurons. In 6/63 cases (9.5%), SC activation elicited a reliable suppression of activity, while the remaining 30/63 cases (47.6%) were unaffected. In almost a third of cases (16/57, 28.1%) intense phasic activation of the SC was associated with correlated phasic activation of neurons in substantia nigra and the ventral tegmental area. These data suggest that the SC is in a position to play an important role in discriminating the appropriate stimulus qualities required to activate DA cells at short latency.