Reversible Huntington's Disease—lesion to the globus pallidus?

Abstract

Authors' reply Sir—We agree with Eric Altschuler that a stereotactic lesion in the globus pallidus could ameliorate the choreatic symptoms caused by striatal degeneration. Indeed, there is evidence to indicate that patients with hemiballism and dystonia (symptoms closely linked to chorea) may benefit from globus pallidus internus pallidotomy,1Suarez JI Metman LV Reich SG et al.Pallidotomy for hemiballism: efficacy and characteristics of neuronal activity.Ann Neurol. 1997; 42: 807-811Crossref PubMed Scopus (104) Google Scholar although the underlying mechanism is as yet unclear. Moreover, Joel and colleagues,2Joel D Ayalon L Tarrasch R et al.Electrolytic lesion of globus pallidus ameliorates the behavioural and neurodegenerative effects of quinolinic acid lesion of the striatum: a potential novel treatment in a rat model of Huntington's disease.Brain Res. 1998; 787: 143-148Crossref PubMed Scopus (27) Google Scholar cited by Altschuler, reported that in the rat model of Huntington's disease, stereotactic lesions in the globus pallidus externus may ameliorate the behavioural performance in the animal model and might even slow down the progressive striatal degeneration. Given these findings, we would put the globus pallidus in concrete terms, although we believe that the degeneration of other basal ganglia structures could also have caused the cessation of Huntington's disease chorea in our patient. But this is not the place to go into further detail. However, the current model of basal ganglia function is unable to explain the beneficial effects of pallidotomy in hyperkinetic movement disorders. According to this model, globus pallidus internus is one of the major basal ganglia output nuclei.3Alexander GE Basal ganglia—thalamocortical circuits: their role in control of movements.J Clin Neurophysiol. 1994; 11: 420-431Crossref PubMed Scopus (142) Google Scholar Globus pallidus internus exerts a tonic GABAergic inhibitory effect on the ventrolateral motor thalamus. Destruction of the inhibitory structure would, according to this model, induce an excess of excitatory influences on the frontocortical regions such as the motor cortex, which would result in a hyperkinetic syndrome rather than ameliorating it. In agreement with this model, globus pallidus internus is currently used as a target for treatment of hypokinetic movement disorders as seen in Parkinson's disease.3Alexander GE Basal ganglia—thalamocortical circuits: their role in control of movements.J Clin Neurophysiol. 1994; 11: 420-431Crossref PubMed Scopus (142) Google Scholar Since patients with hyperkinetic movement disorders including dystonia and hemiballism can also benefit from globus pallidus internus pallidotomy,1Suarez JI Metman LV Reich SG et al.Pallidotomy for hemiballism: efficacy and characteristics of neuronal activity.Ann Neurol. 1997; 42: 807-811Crossref PubMed Scopus (104) Google Scholar recent reports emphasise the insufficiency of the current model of basal ganglia organisation.4Parent A Cicchetti F The current model of basal ganglia organisation under scrutiny.Mov Disord. 1998; 13: 199-202Crossref PubMed Scopus (146) Google Scholar In fact, the most constant benefit observed after lesions of the posteroventral globus pallidus internus is a reduction of L-dopa-induced dyskinesias,5Dogali M Fazzini E Koldony E et al.Stereotactic ventral pallidotomy for Parkinson's disease.Neurology. 1995; 45: 753-761Crossref PubMed Scopus (385) Google Scholar an occurrence not explicable by the current model. Dysfunctional patterns of activity rather than the rate of neuronal firing in the globus pallidus have been implicated in the genesis of hypokinetic and hyperkinetic movement disorders. In turn, abolishing this aberrant pattern of activity by globus pallidus internus pallidotomy could account for the beneficial effects of this procedure in the setting of hypokinetic and hyperkinetic movement disorder.1Suarez JI Metman LV Reich SG et al.Pallidotomy for hemiballism: efficacy and characteristics of neuronal activity.Ann Neurol. 1997; 42: 807-811Crossref PubMed Scopus (104) Google Scholar With respect to our patient, cranial MRI scans obtained in 1991 and 1996 did not show globus pallidus internus and globus pallidus externus lesions. To definitively solve this intriguing question, we need new MRI scans of our patient so that we can closely scrutinise possible basal ganglia alterations. These examinations are currently in progress and this important discussion can be continued only with those results. Reversible Huntington's Disease—lesion to the globus pallidus?Raphael Bonelli and colleagues (Nov 7, p 1520)1 describe a remarkable case of possibly reversible Huntington's disease. The patient presented at age 63 years in 1991 with chorea. Subsequent genetic testing, done twice, showed that the patient had 42 [CAG]n-repeats in the gene associated with Huntington's disease (the cutoff for disease is ≥38 repeats). The patient was placed on cyanamide, dosulepin, and diazepam without improvement. He was readmitted in 1992 and his medications were changed to tiapride, citalopram, and diazepam, with slight improvement in symptoms. Full-Text PDF