Theme #1: Case Studies

Case studies were reported beginning in 1962 when analysis of a hypermetabolic patient indicated increased mitochondria. This is the first case study in the literature and therefore becomes clinically relevant at this time. The authors noted an insufficiency of the mitochondria in adjusting to a dysfunctional metabolic state of non-thyroid origin. 1 At the first Child Neurological Society meeting, mitochondrial encephalomyopathy was introduced as “a group of neuromuscular disorders with defects in the oxidative pathways of energy production.” It presented with encephalomyopathy accompanied by many other symptoms.2  

One case reports a 16- year-old boy with progressive dementia and elevated lactic acid levels whose sister died of a similar condition at 18 years old; the lactic acid levels were higher in the CSF, suggesting defective mitochondrial function in the brain cells. Findings of low oxygen consumption indicated dysfunction of the oxidative pathways as the underlying cause of their disease processes. Whether abnormal mitochondria are present in the brain tissue at this time required a brain biopsy which would have been high invasive.3 Physicians reported two unrelated 9-year-old boys with lactic acidosis who were short in stature, and experienced focal cerebral seizures followed by transient hemiparesis. Histochemistry analysis of their muscle biopsies showed “ragged-red” fibers, containing clusters of mitochondria that lost the typical crisp delineation of crista membranes and contained amorphous inclusion material and parallel-packed cristae and sometimes paracrystalline inclusions. Mitochondrial defect was suspected, as abnormalities were able to be recreated in muscle cells cultured from the patients.4 Two patients, in particular, had clinical features including convulsions, mental deterioration, and muscular atrophy. These case studies of myoclonus epilepsy syndrome were also associated with ragged-red fibres that are known to be related to mitochondrial encephalomyopathies.5

Figure 1. This image was obtained from: “MELAS Pathology.” Accessed April 26, 2019. https://neuromuscular.wustl.edu/pathol/melas.htm. This figure compares scattered fibers with a clear rim (left) to ragged-red muscle fibers of MELAS.

Although many cases appear in the younger years, there are several reported studies in patients over the age of 40. A 63-year-old Chinese female was initially suspected of ischemic infarction but was ultimately diagnosed with MELAS. She was notably short in stature, had auditory and visual hallucinations, as well as disorganized speech and elevated lactic acid upon resting. To prevent delays in treatment, MELAS should be considered in patients with recurrent stroke-like episodes, psychotic symptoms, and cognitive dysfunction.7

References:

  1. Luft, R., Ikkos, D., Palmieri, G., Ernster, L. & Afzelius, B. A Case of Severe Hypermetabolism of Nonthyroid Origin with a Deficit in the Maintenance of Mitochondrial Respiratory Control: A Correlated Clinical, Biochemical, and Morphological Study. J. Clin. Invest. 41, 1776–1804 (1962).
    https://www.jci.org/articles/view/104637
  2. Hart, Z. H., Chang, C.-H., Perrin, E. V. D., Neerunjun, J. S. & Ayyar, R. Familial Poliodystrophy, Mitochondrial Myopathy, and Lactate Acidemia. Arch. Neurol. 34, 180–185 (1977).
    https://jamanetwork.com/journals/jamaneurology/fullarticle/575349
  3. Askanas, V., Engel, W. K., Britton, D. E., Adornato, B. T. & Eiben, R. M. Reincarnation in Cultured Muscle of Mitochondrial Abnormalities: Two Patients With Epilepsy and Lactic Acidosis. Arch. Neurol. 35, 801–809 (1978).
    https://jamanetwork.com/journals/jamaneurology/fullarticle/577058
  4. Fukuhara, N., Tokiguchi, S., Shirakawa, K. & Tsubaki, T. Myoclonus epilepsy associated with ragged-red fibres (mitochondrial abnormalities): Disease entity or a syndrome?: Light- and electron-microscopic studies of two cases and review of literature. J. Neurol. Sci. 47, 117–133 (1980). https://doi.org/10.1016/0022-510X(80)90031-3
  5. Mitochondrial Disorders Overview – GeneReviews® – NCBI Bookshelf. Available at: https://www.ncbi.nlm.nih.gov/books/NBK1224/. (Accessed: 12th April 2019).
    https://www.ncbi.nlm.nih.gov/books/NBK1224/
  6. Melas Syndrome – StatPearls – NCBI Bookshelf. Available at:
    https://www.ncbi.nlm.nih.gov/books/NBK532959/
  7. Fang, Gao-Li, Yang Zheng, and Yin-Xi Zhang. “Mitochondrial Encephalomyopathy with Lactic Acidosis and Stroke-like Episodes in an Older Adult Mimicking Cerebral Infarction: A Chinese Case Report.” Clinical Interventions in Aging, November 27, 2018. https://doi.org/10.2147/CIA.S186636.