Therapy of complex I deficiency: Peripheral neuropathy during dichloroacetate therapy

Abstract

A therapeutic trial with polyvitamins and dichloroacetate (DCA) in combination with thiamine in a 13-year-old girl with complex I deficiency is reported. The polyvitamin therapy included thiamine, riboflavin, ascorbate, coenzyme Q 10 and carnitine. This therapeutic regine was used over a period of 17 months without any effect. Although DCA lowered the lactate concentration in blood and CNS--measured by magnetic resonance spectroscopy--no clinical benefit was achieved. After 20 weeks of DCA therapy a distal polyneuropathy with areflexia developed although 100 mg thiamine daily as comedication was given from the beginning of DCA therapy. Nerve conduction velocity of the peroneal nerve was not detectable, sensible evoked potentials of the tibialis posterious nerve were normal. This side-effect resolved completely within 6 months after omission of DCA. Our observation suggests a direct toxic effect of DCA only on the peripheral nervous system in our patient since several cerebral MRI and magnetic resonance spectroscopy studies showed no abnormalities. CONCLUSION. DCA lowers the lactate concentration in children with complex I deficiency of the respiratory chain in a dose of 100 mg/kg body weight without clinical benefit. Reversible peripheral polyneuropathy may develop under DCA therapy despite thiamine medication.

Magnetic resonance spectroscopy in patients with MELAS

“…Similar observations were made in other cases of mitochondrial disease phenotypes [10,45] underlining the potential of MRS for monitoring treatment response on a quantitative level. Treatment with oral Cr supplementation was monitored in both GM lesions and NAGM in patient 5, in this case without consistent indicators of a beneficial effect [18].…”

Treatment options for lactic acidosis and metabolic crisis in children with mitochondrial disease

“…In general, dichloroacetate therapy is tolerated well in most cases and may lead to short-term improvement. However, long-term use may induce peripheral neuropathy, and there have been no studies showing clear benefits of long term DCA usage on the overall disease prognosis (Kurlemann et al 1995;Kaufmann et al 2006). A promising future option could be phenylbuytrate, which has a comparable mode of action but potentially less side effects (Ferriero et al 2013).…”

Cardiac Metabolism and its Interactions With Contraction, Growth, and Survival of Cardiomyocytes

“…116,117 In a recent study examining hyperthyroidism and cardiac hypertrophy in rats, DCA administration completely reversed reductions in PDH flux, and significantly reduced cardiac hypertrophy without affecting cardiac output. 118 Although human data are limited due to the chronic neurotoxicity of DCA, 119-121 one study in patients with angina and coronary artery disease revealed that infusion of DCA during left heart catheterization was associated with increased stroke volume and myocardial efficiency index (LV work/myocardial oxygen consumption). 122 …”