Abstract
The organ most frequently affected in mitochondrial disorders, particularly respiratory
chain diseases (RCDs), in addition to the skeletal muscle, is the central nervous
system (CNS). CNS manifestations of RCDs comprise stroke-like episodes, epilepsy,
migraine, ataxia, spasticity, movement disorders, psychiatric disorders, cognitive
decline, or even dementia (mitochondrial dementia). So far mitochondrial dementia
has been reported in MELAS, MERRF, LHON, CPEO, KSS, MNGIE, NARP, Leigh syndrome, and
Alpers–Huttenlocher disease. Mitochondrial dementia not only results from mutations
in the mitochondrial genome but also from mutations in nuclear genes, such as POLG,
thymidine kinase 2, or DDP1. Often mitochondrial dementia starts with specific cognitive
deficits, particularly in visual construction, attention, abstraction, or flexibility
but without a general intellectual deterioration. Cognitive impairment in RCDs is
diagnosed upon neuropsychological testing, imaging studies, such as MRI, PET, or MR-spectroscopy,
CSF-investigations, or electroencephalography. Therapy of mitochondrial dementia relies
on symptomatic measures. Only single patients profit from cholinesterase inhibitors
or memantine, antioxidants, vitamins, coenzyme-Q, or other substitutes. Overall, mitochondrial
dementia is an important differential of dementias and should be considered in patients
with multi-system disease.
Abbreviations:
AAT (Achener Aphasia Test), AHS (Alpers–Huttenlocher disease), CNS (central nervous system), CPEO (chronic progressive external ophthalmoplegia), ECGF1 (thymidine kinase 2), EEG (electroencephalography), IOSCA (infantile onset spino-cerebellar ataxia), KSS (Kearns Sayre syndrome), LHON (Leber's hereditary optic neuropathy), LS (Leigh syndrome), MAS (Digit Span Memory Assessment Scale), MELAS (mitochondrial encephalomyopathy, lactacidosis, stroke-like episodes), MERRF (myoclonic epilepsy with ragged red fibres), MID (mitochondrial disorder), MILS (maternally inherited Leigh syndrome), MNGIE (mitochondrial neuro-gastro-intestinal encephalomyopathy), mtDNA (mitochondrial DNA), MRS (magnetic resonance spectroscopy), MTS (Mohr–Tranebjaerg syndrome), NARP (neurogenic weakness, ataxia and retinitis pigmentosa), nDNA (nuclear DNA), OXPHOS (oxidative phosphorylation), PDC (pyruvat-dehydrogenase complex), PET (positron-emission tomography), POLG (polymerase gamma), PS (Pearson syndrome), RCD (respiratory chain disorder), SANDO (sensory ataxia with neuropathy, dysarthria and ophthalmoparesis), SCAE (spinocerebellar ataxia and epilepsy), SLE (stroke-like episode), SPECT (single-photon-emission computed tomography), VEPs (visually-evoked potentials), WAIS (Wechsler Adult Intelligence Scale), WS (Wolfram syndrome)Keywords
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Published online: March 09, 2009
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© 2009 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
