Leigh syndrome is a rare neurodegenerative disease caused by mitochondrial dysfunction from a genetic defect. It is characterized by bilateral brain lesions seen on imaging and variable symptoms. While it typically presents in infancy, it can occasionally present in adulthood. The diagnosis involves identifying characteristic brain lesions. Treatment focuses on nutritional supplementation like biotin and thiamine, as well as managing symptoms, but there is no cure for the underlying genetic condition.
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. 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.
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. 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. 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. 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. 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.
