Disorders of Movement in Leigh Syndrome

Macaya, Alfons; Munell, Francina; Burke, Robert E.; Vivo, Darryl C. De

doi:10.1055/s-2008-1071515

Cited by 56 publications

(21 citation statements)

References 37 publications

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“…No metabolic abnormalities were identified, however, despite extensive pre‐diet investigations. Consistent with the possibility of an inborn error of energy metabolism, the radiographic and movement abnormalities that appeared in our patient after diet initiation resemble those of Leigh syndrome and familial striatal necrosis, disorders caused by genetic defects in mitochondrial metabolism 7, 8. Our patient corresponds best with a group of patients with familial striatal necrosis, described by Aicardi, who developed neurological deterioration after an acute systemic illness or other metabolic stressor 8…”

Section: Discussionsupporting

confidence: 87%

Basal ganglia injury as a complication of the ketogenic diet

2002

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Movement disorders or basal ganglia injury have not been reported as complications of the ketogenic diet, an alternative treatment for intractable epilepsy. We report on a novel complication of the ketogenic diet manifesting as a severe extrapyramidal movement disorder and bilateral putaminal lesions. A single case is described. A video demonstrating the movement disorder is included. A 5-year-old girl with a cryptogenic epileptic encephalopathy developed focal dystonia, diffuse chorea, and ataxia after starting the ketogenic diet. Cranial magnetic resonance imaging (MRI) demonstrated bilateral putaminal lesions that were not present before starting the diet. MR spectroscopy showed a lactate peak in the basal ganglia, suggesting a failure of mitochondrial energy metabolism as the mechanism of cerebral injury. The radiographic abnormalities resolved after stopping the diet, although the movement disorder persisted. Basal ganglia injury and extrapyramidal movement abnormalities are potential complications of the ketogenic diet. Concomitant use of valproate or a latent inborn error of metabolism may be risk factors for these rare complications.

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Section: Discussionsupporting

confidence: 87%

Basal ganglia injury as a complication of the ketogenic diet

2002

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“…Parkinsonism, dystonia, myoclonus, and less frequently, chorea have been described as classical movement disorders in MiD patients, often associated with nonspecific white matter and basal ganglia abnormalities on MRI . Ataxia has been repeatedly described as one of the most frequent symptoms of MiD, although its precise prevalence has not been established .…”

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confidence: 99%

Movement disorders in genetically confirmed mitochondrial disease and the putative role of the cerebellum

et al. 2017

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Background: Mitochondrial disease can present as a movement disorder. Data on this entity's epidemiology, genetics, and underlying pathophysiology, however, is scarce. Objective: The objective of this study was to describe the clinical, genetic, and volumetric imaging data from patients with mitochondrial disease who presented with movement disorders. Methods: In this retrospective analysis of all genetically confirmed mitochondrial disease cases from three centers (n = 50), the prevalence and clinical presentation of video‐documented movement disorders was assessed. Voxel‐based morphometry from high‐resolution MRI was employed to compare cerebral and cerebellar gray matter volume between mitochondrial disease patients with and without movement disorders and healthy controls. Results: Of the 50 (30%) patients with genetically confirmed mitochondrial disease, 15 presented with hypokinesia (parkinsonism 3/15), hyperkinesia (dystonia 5/15, myoclonus 3/15, chorea 2/15), and ataxia (3/15). In 3 patients, mitochondrial disease presented as adult‐onset isolated dystonia. In comparison to healthy controls and mitochondrial disease patients without movement disorders, patients with hypo‐ and hyperkinetic movement disorders had significantly more cerebellar atrophy and an atrophy pattern predominantly involving cerebellar lobules VI and VII. Conclusion: This series provides clinical, genetic, volumetric imaging, and histologic data that indicate major involvement of the cerebellum in mitochondrial disease when it presents with hyper‐ and hypokinetic movement disorders. As a working hypothesis addressing the particular vulnerability of the cerebellum to energy deficiency, this adds substantially to the pathophysiological understanding of movement disorders in mitochondrial disease. Furthermore, it provides evidence that mitochondrial disease can present as adult‐onset isolated dystonia. © 2017 International Parkinson and Movement Disorder Society

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“…Another metabolic abnormality found in the caudate nucleus of HD patients was a reduction in oxygen utilization, as well as in the activity of mitochondrial complexes II (succinate dehydrogenase), III (cytochrome be 1 complex), and IV (cytochrome e oxidase) (Brennan et al, 1985;Gu et al, 1996), whereas complex I (NADH dehydrogenase) activity was decreased in platelet mitochondria (Parker et al, 1990). In addition, mitochondrial DNA mutations resulting in Leigh's syndrome and Leber's disease can involve basal ganglia degeneration (Novotny et al, 1986;Bruyn et al, 1991;Macaya et al, 1993), and administration of mitochondrial poisons, such as blockers of succinate dehydrogenase, selectively induces striatal degeneration in a pattern similar to that seen in HD (Beal et al, 1993a).…”

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confidence: 99%

Energetic Dysfunction in Quinolinic Acid‐Lesioned Rat Striatum

Bordelon¹,

Chesselet

Nelson³

et al. 1997

Journal of Neurochemistry

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Impairment of mitochondrial energy metabolism may contribute to the selective neuronal degeneration observed in Huntington's disease and other neurodegenerative disorders. Intrastriatal injection of the excitotoxin, quinolinic acid, produces a pattern of neuronal death similar to that seen in Huntington's disease. However, little is known about the effects of quinolinic acid on striatal energetics. In the present work, time-dependent changes in energy metabolism caused by injection of quinolinic acid into rat striatum were examined. Oxygen consumption by free and synaptic mitochondria was quantified and correlated with the concentrations of nucleotides and amino acids at different times after injection. Compared with saline-treated controls, a decrease in ADP-stimulated (state 3) to basal (state 4) oxygen consumption (respiratory control ratio) by free mitochondria was apparent in quinolinic acid-injected striata as early as 6 h after treatment. No significant changes were seen in nucleotide concentrations at this time. By 12 h after injection, the decline in the respiratory control ratio was more pronounced (45%), and reductions in ATP, NAD, aspartate, and glutamate (30-60%) were also observed. These results show that injection of quinolinic acid in vivo produces progressive mitochondrial dysfunction, which may be a common and critical event in the cell death cascade initiated in Huntington's disease and in animal models of this neurodegenerative disorder. The indicators of mitochondrial function examined in this study, therefore, may be useful in evaluating the efficacy of neuroprotective agents.

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Disorders of Movement in Leigh Syndrome

Cited by 56 publications

References 37 publications

Basal ganglia injury as a complication of the ketogenic diet

Basal ganglia injury as a complication of the ketogenic diet

Movement disorders in genetically confirmed mitochondrial disease and the putative role of the cerebellum

Energetic Dysfunction in Quinolinic Acid‐Lesioned Rat Striatum

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