Dystonia and chorea in acquired systemic disorders

Abstract

Dystonia and chorea are uncommon abnormal movements which can be seen in a wide array of disorders. One quarter of dystonias and essentially all choreas are symptomatic or secondary, the underlying cause being an identifiable neurodegenerative disorder, hereditary metabolic defect, or acquired systemic medical disorder. Dystonia and chorea associated with neurodegenerative or heritable metabolic disorders have been reviewed frequently.1 Here we review the underlying pathogenesis of chorea and dystonia in acquired general medical disorders (table 1), and discuss diagnostic and therapeutic approaches. The most common aetiologies are hypoxia-ischaemia and medications. [2][3][4] Infections and autoimmune and metabolic disorders are less frequent causes. Not uncommonly, a given systemic disorder may induce more than one type of dyskinesia by more than one mechanism.The areas of the brain associated with particular movement disorders have been determined by cerebral imaging and necropsies of patients, and by animal lesioning studies. 5-7Based on such data, chorea seems to result from hypofunction of the indirect pathway from the putamen to the internal globus pallidus, and dystonia correlates more strongly with hyperfunction of the direct relative to the indirect pathway between the putamen and internal globus pallidus, both resulting in inappropriate disinhibition of thalamic projections to the premotor and motor cortex (figure). Chorea has been most consistently associated with lesions in the caudate nucleus or putamen, resulting in disinhibition of the external globus pallidus. Lesions of the subthalamointernal pallidal pathway also result in chorea.Associated neurotransmitter abnormalities include deficient striatal GABA-ergic function and striatal cholinergic interneuron activity, and dopaminergic hyperactivity in the nigrostriatal pathway. Dystonia has been correlated with lesions of the contralateral putamen, external globus pallidus, posterior and posterior lateral thalamus, red nucleus, or subthalamic nucleus, or a combination of these structures. The result is decreased activity in the pathways from the medial pallidus to the ventral anterior and ventrolateral thalamus, and from the substantia nigra reticulata to the brainstem, culminating in cortical disinhibition. Altered sensory input from the periphery may also produce cortical motor overactivity and dystonia in some cases. 8 To date, the changes found in striatal neurotransmitter concentrations in dystonia include an increase in noradrenaline and a decrease in dopamine concentrations. Hypoxic-ischaemic causes MECHANISMSChorea and dystonia may result from hypoxiaischaemia due to global cerebral hypoperfusion or cellular hypoxia, such as in toxic mitochondrial dysfunction. Two hypotheses have been put forward to explain hypoxic-ischaemic injury to the basal ganglia: selective hypoperfusion of certain vascular territories and an intrinsic metabolic susceptibility of the striatum to hypoxia-ischaemia due to its high oxidative metabolism. 7 The internal segm...

Proton Magnetic Resonance Spectroscopy in Huntington's Disease Accompanying Neuroborreliosis

“…Vasculitis was reported as the main pathogenetic mechanism of basal ganglia ischaemia related to neuroborreliosis. Other proposed mechanisms include vasculopathy due to direct basal ganglia invasion by the organism, neuronal injury by an cytotoxin, antibiodies cross-reactivity with basal ganglia epitopes (Janavs et al 1998). The selective pathophysiology that occurs in HD is still unknown.…”

“…The ability of 1H-MRS to track spectral changes makes it potentially useful for diagnostics and prognostics or as a tool to monitor the effects of treatment when Janavs et al 1998). Too few cases of movement disorders such as chorea and dystonia were described during the course of neuroborreliosis (Piccolo et al 1998).…”

TAK-063, a Novel Phosphodiesterase 10A Inhibitor, Protects from Striatal Neurodegeneration and Ameliorates Behavioral Deficits in the R6/2 Mouse Model of Huntington’s Disease

“…In fact, a cataleptic response induced by activation of the indirect pathway by haloperidol was canceled by excessive activation of the direct pathway by a D 1 receptor agonist SKF82958 in rats . Moreover, several reports have suggested that excessive activation of the direct pathway MSNs is involved in the production of dystonia, one of the major clinical features of HD (Janavs and Aminoff, 1998;Louis et al, 1999;Burbaud, 2012). It is not known whether the indirect pathway MSN-biased activation pattern by TAK-063 would translate to therapeutic benefit in humans.…”

Pallido-luysio-nigral atrophy revealed by rapidly progressive hemidystonia: A clinical, radiologic, functional, and neuropathologic study

“…1,2 Hemidystonia is almost always secondary to a structural lesion localized in the striatal, pallidal, thalamic, or subthalamic areas. [3][4][5] Unilateral dystonic symptoms may also occur in the course of neurodegenerative diseases such as corticobasal degeneration, progressive supranuclear palsy, or other parkinsonian syndromes.…”