Midbrain Ataxia: An Introduction to the Mesencephalic Locomotor Region and the Pedunculopontine Nucleus

Department of Radiology, Geffen School of Medicine, University of California-Los Angeles Medical Center, Los Angeles, CA 90095, USA.
American Journal of Roentgenology (Impact Factor: 2.73). 04/2005; 184(3):953-6. DOI: 10.2214/ajr.184.3.01840953
Source: PubMed

ABSTRACT OBJECTIVE: Although gait ataxia is usually associated with cerebellar lesions, we review a less familiar cause. We present three patients with dorsal midbrain lesions and correlate these presentations with recent findings in the functional anatomy of the midbrain. CONCLUSION: We suggest that these lesions involve a well-studied but generally unfamiliar area of the dorsal midbrain known as the mesencephalic locomotor region. More specifically, we hypothesize that involvement of the pedunculopontine nucleus, a major component of the mesencephalic locomotor region, may be at least partially responsible for producing midbrain ataxia.

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    • "This finding fits with the observation that longer disease duration increases the likelihood of developing FOG (Macht et al., 2007), with the mesencephalic locomotor region becoming more affected as Parkinson's disease progresses (Braak et al., 2000). Third, ischaemic lesions in the dorsomedial mesencephalic locomotor region cause gait ataxia, but not a hypokinetic-rigid gait (Hathout and Bhidayasiri, 2005). However, if gait-related activity in the mesencephalic locomotor region of patients with FOG were exclusively pathological in nature, then how could patients with FOG have solved the task as adequately as patients without FOG and controls, despite their altered cortical responses during imagery of gait? "
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    ABSTRACT: Freezing of gait is a common, debilitating feature of Parkinson's disease. We have studied gait planning in patients with freezing of gait, using motor imagery of walking in combination with functional magnetic resonance imaging. This approach exploits the large neural overlap that exists between planning and imagining a movement. In addition, it avoids confounds introduced by brain responses to altered motor performance and somatosensory feedback during actual freezing episodes. We included 24 patients with Parkinson's disease: 12 patients with freezing of gait, 12 matched patients without freezing of gait and 21 matched healthy controls. Subjects performed two previously validated tasks--motor imagery of gait and a visual imagery control task. During functional magnetic resonance imaging scanning, we quantified imagery performance by measuring the time required to imagine walking on paths of different widths and lengths. In addition, we used voxel-based morphometry to test whether between-group differences in imagery-related activity were related to structural differences. Imagery times indicated that patients with freezing of gait, patients without freezing of gait and controls engaged in motor imagery of gait, with matched task performance. During motor imagery of gait, patients with freezing of gait showed more activity than patients without freezing of gait in the mesencephalic locomotor region. Patients with freezing of gait also tended to have decreased responses in mesial frontal and posterior parietal regions. Furthermore, patients with freezing of gait had grey matter atrophy in a small portion of the mesencephalic locomotor region. The gait-related hyperactivity of the mesencephalic locomotor region correlated with clinical parameters (freezing of gait severity and disease duration), but not with the degree of atrophy. These results indicate that patients with Parkinson's disease with freezing of gait have structural and functional alterations in the mesencephalic locomotor region. We suggest that freezing of gait might emerge when altered cortical control of gait is combined with a limited ability of the mesencephalic locomotor region to react to that alteration. These limitations might become particularly evident during challenging events that require precise regulation of step length and gait timing, such as turning or initiating walking, which are known triggers for freezing of gait.
    Brain 01/2011; 134(Pt 1):59-72. DOI:10.1093/brain/awq324 · 9.20 Impact Factor
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    • "cantly altered in healthy old people. Gait parameters are mainly modulated at subcortical locomotor centers (e.g., subthalamic nucleus, pedunculopontine nucleus), as has been suggested by electrical stimulation experiments in the cat (Armstrong, 1988; Armstrong et al., 1988; Shik and Orlovsky, 1976), and by patients with bilateral brainstem lesions (Hathout and Bhidayasiri, 2005; Masdeu et al., 1994). The subcortical locomotor centers are, in an evolutionary sense, old structures; consequently, they may be less prone to atrophy or dysfunction during aging. "
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    ABSTRACT: Standing, walking, and running are sensorimotor tasks that develop during childhood. Thereafter they function automatically as a result of a supraspinal network that controls spinal pattern generators. The present study used functional magnetic resonance imaging (fMRI) to investigate age-dependent changes in the supraspinal locomotor and postural network of normal subjects during mental imagery of locomotion and stance. Sixty healthy subjects (ages: 24-78 years), who had undergone a complete neurological, neuro-ophthalmological, and sensory examination to rule out disorders of balance and gait, were trained for the conditions lying, standing, walking, and running in order to imagine these conditions on command in 20-second sequences with the eyes closed while lying supine in an magnetic resonance imaging (MRI) scanner. The following blood oxygen level-dependent (BOLD) signal changes during locomotion and stance were found to be independent of age: (1) prominent activations in the supplementary motor areas, the caudate nuclei, visual cortical areas, vermal, and paravermal cerebellum; (2) significant deactivations in the multisensory vestibular cortical areas (posterior insula, parietoinsular vestibular gyrus, superior temporal gyrus), and the anterior cingulate during locomotion. The following differences in brain activation during locomotion and stance were age-dependent: relative increases in the cortical BOLD signals in the multisensory vestibular cortices, motion-sensitive visual cortices (MT/V5), and somatosensory cortices (right postcentral gyrus). In advanced age this multisensory activation was most prominent during standing, less during walking, and least during running. In conclusion, the functional activation of the basic locomotor and postural network, which includes the prefrontal cortex, basal ganglia, brainstem, and cerebellar locomotor centers, is preserved in the elderly. Two major age-dependent aspects of brain activation during locomotion and stance were found: the mechanism of cortical inhibitory reciprocal interaction between sensory systems during locomotion and stance declines in advanced age; and consequently, multisensory cortical control of locomotion and stance increases with age. These findings may indicate a more conscious locomotor and postural strategy in the elderly.
    Neurobiology of aging 11/2010; 33(6):1073-84. DOI:10.1016/j.neurobiolaging.2010.09.022 · 5.01 Impact Factor
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    • "Parkinson's disease and progressive supranuclear palsy, both characterized by a gait disturbance including problems with starting locomotion , are associated with reduced cell counts in the MLR, namely the pedunculopontine nucleus (Zweig et al., 1987; 1989; Pahapill and Lozano, 2000). Anecdotal reports on single patients with vascular midbrain lesions support the view that the MLR also mediates gait initiation in humans (Masdeu et al., 1994; Hathout and Bhidayasiri, 2005). Bilateral stroke in the pedunculopontine area caused freezing of gait in a single patient (Kuo et al., 2008). "
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    ABSTRACT: Patients with neurological gait disorders often present to their doctor with the key symptoms of dizziness and gait unsteadiness (e.g. cerebellar ataxia, progressive supranuclear palsy). In vestibular syndromes, on the other hand, the gait disturbance is a leading sign and many aspects of the syndrome can be recognized from the analysis of posture and gait (e.g. direction of falls). For therapy in particular it is important to better understand the physiological control of posture and gait to adapt rehabilitation programs. We recently succeeded in visualizing the hierarchic network for postural control in humans by means of functional imaging techniques. Growing evidence suggests that so-called "locomotor regions", groups of neurons able to initiate or modulate spinal stepping in the cat in response to electrical or chemical stimulation, also exist in humans. The most important locomotor regions are the mesencephalic, the subthalamic, and the cerebellar locomotor regions. Locomotor signals are transmitted from the midbrain to the spinal cord via the ponto-medullary reticular formation and integrate multisensory input at different levels. Functional imaging also demonstrated that the multisensory cortical areas are inhibited during locomotion, which is relevant for physical therapy of vestibular disorders which therefore should include exercises with different gait patterns and different speeds. The supraspinal network for locomotion is just beginning to be recognized as an important factor in the pathophysiology of common gait disorders. In Parkinson's disease, for example, low-frequency stimulation of the mesencephalic locomotor region (pedunculopontine nucleus) is already used to treat freezing and gait disturbance in selected patients. In this review we summarize different attempts to visualize human supraspinal locomotor control using functional neuroimaging techniques, both in healthy subjects and in patients suffering from balance disorders.
    Restorative neurology and neuroscience 01/2010; 28(1):105-14. DOI:10.3233/RNN-2010-0506 · 2.49 Impact Factor
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