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Leigh Syndrome


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Leigh Syndrome / Leigh's Disease

Published in: Health & Medicine

Leigh Syndrome

  1. 1. A D E W I J A Y A , M D – A U G U S T 2 0 1 8 Leigh Syndrome
  2. 2. Outline:  Introdcution  Characteristic  Diagnosis  LS in adulthood  Differential Diagnosis  Treatment  Summary
  3. 3. Introduction  Leigh syndrome (LS)  Subacute necrotising encephalopathy,  First described by the British psychiatrist and neuropathologist Denis Archibald Leigh in 1951 Leigh D. Subacute necrotizing encephalomyelopathy in an infant. J Neurol Neurosurg Psychiatry1951;14:216- 21
  4. 4. Characteristic  Neurodegenerative disease with variable symptoms  Mitochondrial dysfunction caused by a hereditary genetic defect  Bilateral CNS lesions that can be associated with further abnormalities in diagnostic imaging If partially met  Leigh-like syndrome Dahl HH. Getting to the nucleus of mitochondrial disorders: identification of respiratory chain-enzyme genes causing Leigh syndrome. Am J Hum Genet 1998;63:1594–7. Finsterer J. Leigh and Leigh-like syndrome in children and adults. Pediatr Neurol2008;39:223–35.
  5. 5. Diagnosis Baertling F, et al. J Neurol Neurosurg Psychiatry 2013; 0:1–9. doi:10.1136/jnnp-2012-304426
  6. 6. LS in Adulthood  Rare, diagnostic challenge  Some atypical features: intellectual decline, vertical gaze palsies, headache, memory loss, visual hallucination  mtDNA mutation Kelvie P, Infeld B, Marotta R, et al. Late-adult onset Leigh syndrome. J Clin Neurosci 2012;19:195–202. Gray F, Louarn F, Gherardi R, et al . Adult form of Leigh’s disease: a clinicopathological case with CT scan examination. J Neurol Neurosurg Psychiatry 1984;47:1211–15.
  7. 7. Differential Diagnosis  Neonatal / perinatal asphyxia  Kernicterus  Wernicke encephalopathy  Methylmalonic acidemia, propionic acidemia and glutaric acidemia type I.  Wilson’s disease  Methanol, carbon monoxyde, or cyanide poisoning  Biotin-responsive basal ganglia disease (BBGD) Baertling F, et al. J Neurol Neurosurg Psychiatry 2013; 0:1–9. doi:10.1136/jnnp-2012-304426
  8. 8. Treatment  Genetic counselling  a high dose of biotin treatment (10 up to 20 mg/kg) and thiamine (100–300 mg) should be given immediately, since BBGD can clinically imitate LS and this treatment is potentially life saving. In addition, recent studies underline the specific benefit of thiamine in LS patients.  Nutraceuticals / vitamin cocktails : coenzyme Q10, L-carnitine,α-lipoic acid, creatine-monohydrate, biotin, thiamine, riboflavin and others.  Dietary treatment Baertling F, et al. J Neurol Neurosurg Psychiatry 2013; 0:1–9. doi:10.1136/jnnp-2012-304426
  9. 9. Treatment  Treatment of lactic academia with bicarbonate or dichloroacetate after careful assessment of the clinical situation.  Interdisciplinary palliative care  Swallowing problems: NGT, PEG, or tracheostoma  Respiratory dysrhythmias and central hypoventilation with apnoea might require homecare ventilatory support devices or CPAP and should be monitored by polysomnography  Physiotherapy  Seizure management but avoid valproic acid and barbiturates that impair mitochondrial function, also tetracyclines  Opthalmologist and audiologist Horvath R, Gorman G, Chinnery PF. How can we treat mitochondrial encephalomyopathies? Approaches to therapy. Neurotherapeutics 2008;5:558–68 Stacpoole PW, Kerr DS, Barnes C, et al. Controlled clinical trial of dichloroacetate for treatment of congenital lactic acidosis in children. Pediatrics 2006; 117:1519– 31.
  10. 10. Summary  Leigh syndrome is a rare devastating neurodegenerative disease, typically manifesting in infancy or early childhood.  Adult onset Leigh syndrome.  Hallmarks of the disease are symmetrical lesions in the basal ganglia or brain stem on MRI, and a clinical course with rapid deterioration of cognitive and motor functions.  Numerous causative mutations in mitochondrial and nuclear genes, encoding components of the oxidative phosphorylation system have been described in the past years.  Dysfunctions in pyruvate dehydrogenase complex or coenzyme Q10 metabolism.  No cure and unsatisfactory treatment options.  Treatment: biotin and thiamine + (Coenzyme-Q10) , maybe other nutraceuticals / vitamin cocktails.
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