Rigid and Akinetic Forms of Huntington's Chorea

Bittenbender, J. B.; Quadfasel, F. A.

doi:10.1001/archneur.1962.04210040027003

Cited by 99 publications

(37 citation statements)

References 22 publications

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“…The motor nerves to these two types of muscle fibres can be distinguished from one another by their diameter (Pilar and Hess, 1966), as well as by their physiological properties (Bach-y-Rita and Ito, 1966), but the central nervous system structures controlling these two neuromuscular systems are not known. The loss of saccades in the patients with Huntington's chorea presented in this study and previous description of impaired or slowed conjugate gaze in this same illness (Bender, 1960;Bittenbender and Quadfasel, 1962) raises the possibility that the caudate nucleus which is predominantly affected in Huntington's chorea may be intimately related to the neural system regulating rapid eye movements. This interpretation receives indirect support from animal experiments in which "wide and vacuous eyes" with a "paucity of eye movements" were the consequence of bilateral caudate lesions (Mettler, 1964), while stimulation of the head of the caudate evoked orienting eye movements to the opposite side (Laursen, 1963).…”

Section: Discussionsupporting

confidence: 72%

“…The difference between the six patients with normal eye movements and the three patients with an absence of saccades might be due to biotypes among individuals with Huntington's chorea, based on genetically determined variations in the central nervous system lesions. Such a concept has been proposed as the basis for the rigid and hypotonic forms of Huntington's chorea (Bittenbender and Quadfasel, 1962). Alternatively, since the motor manifestations of Huntington's chorea change during the course of the illness (Denny-Brown, 1962), the disorder of rapid eye movements may not yet have become manifest in these six patients and should become evident on subsequent examinations.…”

Section: Discussionmentioning

confidence: 99%

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A Disorder of Rapid Eye Movements in Huntington's Chorea

Starr

1967

Brain

276

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Section: Discussionsupporting

confidence: 72%

Section: Discussionmentioning

confidence: 99%

A Disorder of Rapid Eye Movements in Huntington's Chorea

Starr

1967

Brain

276

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“…The resulting polyglutamine (polyQ) expansion in the 350 kDa cytosolic protein huntingtin (Htt) is associated with typical adult onset disease for repeat lengths of 40 -55, whereas more extreme expansions cause juvenile onset and a distinct clinical presentation (Bittenbender and Quadfasel, 1962;van Dijk et al, 1986;Brinkman et al, 1997). Neuronal loss is most severe among the medium-sized spiny neurons (MSNs) of the neostriatum (Vonsattel et al, 1985), whereas Htt expression is widespread (Strong et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial Sensitivity and Altered Calcium Handling Underlie Enhanced NMDA-Induced Apoptosis in YAC128 Model of Huntington's Disease

Fernandes

Baimbridge²,

Church³

et al. 2007

J. Neurosci.

108

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Expansion of a CAG repeat in the Huntington's disease (HD) gene results in progressive neuronal loss, particularly of striatal mediumsized spiny neurons (MSNs). Studies in human HD autopsy brain tissue, as well as cellular and animal models of HD, suggest that increased activity of NMDA-type glutamate receptors and altered mitochondrial function contribute to selective neuronal degeneration. In this regard, the YAC128 mouse model, expressing full-length human huntingtin with 128 glutamine repeats, has been the focus of much interest. Although NMDA-induced apoptosis is enhanced in YAC128 MSNs, here we report that the initial steps in the death signaling pathway, including NMDA receptor (NMDAR) current and cytosolic Ca 2ϩ loading, are similar to those observed in wild-type MSNs. In contrast, we found that the NMDAR-mediated Ca 2ϩ load triggered a strikingly enhanced loss of mitochondrial membrane potential in YAC128 MSNs, suggesting that NMDAR signaling via the mitochondrial apoptotic pathway is altered. This effect was accompanied by impaired cytosolic Ca 2ϩ clearance after removal of NMDA, a difference that was not apparent after high potassium-evoked depolarization-mediated Ca 2ϩ entry. Inhibition of the mitochondrial permeability transition (mPT) reduced peak cytosolic Ca 2ϩ and mitochondrial depolarization evoked by NMDA in YAC128 MSNs but not wild-type MSNs. Hence, in contrast to YAC models with moderate CAG expansions, the enhanced NMDA-induced apoptosis in YAC128 MSNs is predominantly determined by augmented mitochondrial sensitivity to Ca 2ϩ -induced activation of the mPT. These results suggest that the CAG repeat length influences the mechanism by which mHtt enhances NMDAR-mediated excitotoxicity.

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“…These involuntary movements are seen first in the fingers and toes, then in the trunk. Approximately 10% of all patients with HD may, however, have the juvenile onset or Westphal variant of HD with symptoms of hypokinesia and rigidity similar to Parkinson's disease (Bittenbender & Quadfasel, 1962;Bruyn, 1962). Difficulties with balance occur, with exaggerated, fidgeting motor action and a tendency to violent involuntary movements.…”

Section: Motor Symptomsmentioning

confidence: 99%