Parkinson syndrome, neuropathy, and myopathy caused by the mutation A8344G (MERRF) in tRNA(Lys)

Ruhr-Universität Bochum, Bochum, North Rhine-Westphalia, Germany
Neurology (Impact Factor: 8.3). 02/2007; 68(1):56-8. DOI: 10.1212/01.wnl.0000250334.48038.7a
Source: PubMed

ABSTRACT We describe a patient who presented with parkinsonism associated with the A8344G myoclonus epilepsy, ataxia, and myopathy with ragged red fibers mutation in the tRNA(Lys) gene. In addition, neurogenic changes and mitochondrial myopathy with ragged red fibers were observed. Neither myoclonus epilepsy nor other clinical signs described in association with A8344G were noted. Similar to previously reported patients with parkinsonism and mtDNA deletions, the symptoms of our patient responded favorably to levodopa therapy.

  • [Show abstract] [Hide abstract]
    ABSTRACT: The cerebellum is responsible for refining ocular movements, thereby guaranteeing the best possible visual acuity and clarity despite changes in body or head positions or movement of the object of interest. The cerebellum is involved in the control of all eye movements, in their real-time, immediate modulation, and in their long-term adaptive calibration. The flocculus-paraflocculus complex and the caudal vermis (nodulus and uvula) together constitute the vestibulocerebellum. Lesions affecting these different regions give rise to 3 principal clinical cerebellar syndromes. This article discusses the various neuro-ophthalmic manifestations of various cerebellar disorders, as well as some therapeutic options for oscillopsia. Copyright © 2014 Elsevier Inc. All rights reserved.
    Neurologic Clinics 10/2014; 32(4). DOI:10.1016/j.ncl.2014.07.002 · 1.61 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: As the second most common age related neurodegenerative disease after Alzheimer's disease, the health, social and economic impact resulting from Parkinson's disease will continue to increase alongside the longevity of the population. Ageing remains the biggest risk factor for developing idiopathic Parkinson's disease. Although research into the mechanisms leading to cell death in Parkinson's disease has shed light on many aspects of the pathogenesis of this disorder, we still cannot answer the fundamental question, what specific age related factors predispose some individuals to develop this common neurodegenerative disease. In this review we focus specifically on the neuronal population associated with the motor symptoms of Parkinson's disease, the dopaminergic neurons of the substantia nigra, and try to understand how ageing puts these neurons at risk to the extent that a slight change in protein metabolism or mitochondrial function can push the cells over the edge leading to catastrophic cell death and many of the symptoms seen in Parkinson's disease. We review the evidence that ageing is important for the development of Parkinson's disease and how age related decline leads to the loss of neurons within this disease, before describing exactly how advancing age may lead to substantia nigra neuronal loss and Parkinson's disease in some individuals.
    Ageing research reviews 02/2014; DOI:10.1016/j.arr.2014.01.004 · 7.63 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We describe a child with dyslexia and difficulty in school who, at the age of 13 years, began to suffer from several head injuries resulting from falls of uncertain cause. Two years later, the patient developed symptoms of a severe mitochondrial disorder (involving bulbar-pyramidal paralysis, ophthalmoplegia, and hyperlactatemia) that coincided with VPA administration. Brain MR imaging revealed rapidly developing Leigh syndrome (LS), and muscle biopsy showed ragged blue fibres (RBF). A diminished expression of the E1 subunit of pyruvate dehydrogenase was found in muscle homogenate (signal 28.7% of normal). The accurate diagnosis of mitochondrially inherited LS (MILS) and the identification of an almost homoplasmic m.8344G>A mutation in the MTTK gene was delayed due to an initial incorrect diagnosis of epilepsy, misdiagnosis of neuroinfection, and failure to note LS on the first brain MRI. Periods of exacerbation or improvement were observed in association with the administration of certain drugs or procedures (VPA administration or intensive rehabilitation associated with worsening; ketogenic diet associated with remission). However, the random association of these factors with natural disease fluctuations cannot be excluded. Conclusions: 1) To improve the early detection of mitochondrial disorder, we recommend screening for mtDNA (and nDNA) mutations in all patients with LS present on brain MRI. 2) Brain MRI protocols should include diffusion-weighted and T2-weighted imaging, and LS-like changes should be analysed by a neuroradiologist experienced in the field. 3) Additional controlled studies are urgently needed to assess the causal relationship between management strategies and the natural history of the disease. Until the association between VPA and disease exacerbation can be ruled out, VPA should be avoided in patients with these symptoms unless the mitochondrial disorder has been excluded.
    01/2013; 51(4):347-54. DOI:10.5114/fn.2013.39726