Leukoencephalopathy with thalamus and brainstem involvement and high lactate (LTBL)
Leukoencephalopathy with brainstem and spinal cord involvement and high lactate (LBSL)
Mitochondrial neurogastrointestinal encephalopathy (MNGIE): TYMP gene recessive mutation (required for mitochondrial DNA replication)
Mitochondrial dysfunction has been associated with myriad clinical pathologies, ranging from autism to Alzheimer dementia to normal aging
This chapter addresses some of those primarily affecting brain, presenting in childhood, and not covered elsewhere
New mutations and phenotypes are constantly being discovered
Many other metabolic diseases primarily affect mitochondria but are not typically considered ME
Neurodegeneration with brain iron accumulation (NBIA), glutaric aciduria type 1, trichothiodystrophy are examples
Classification
Multiple classification schemes for metabolic diseases of mitochondria have been proposed
Clinical phenotype
Longest recognized syndromes are classified by their clinical/pathologic/radiologic presentation
LS is defined in this manner
Locale of genetic defect
Mutation in mitochondrial DNA (mtDNA) or nuclear DNA (nDNA)
Segment of metabolic pathway affected
Respiratory chain (RC) subunits: Complexes I-V
mtDNA transcription defects: POLG-RD
Pyruvate metabolism disorders: PDH and PC deficiency
All have strengths and weaknesses, reflecting complexity of structure and function of organelle
IMAGING
General Features
CT Findings
MR Findings
Imaging Recommendations
DIFFERENTIAL DIAGNOSIS
PATHOLOGY
General Features
CLINICAL ISSUES
Presentation
Demographics
Natural History & Prognosis
Treatment
DIAGNOSTIC CHECKLIST
Image Interpretation Pearls
Selected References
Shelkowitz E et al: Serial magnetic resonance imaging (MRI) in pyruvate dehydrogenase complex deficiency. J Child Neurol. 35(2):137-45, 2020
Gramegna LL et al: Cerebral mitochondrial microangiopathy leads to leukoencephalopathy in mitochondrial neurogastrointestinal encephalopathy. AJNR Am J Neuroradiol. 39(3):427-34, 2018
Sofou K et al: Phenotype-genotype correlations in Leigh syndrome: new insights from a multicentre study of 96 patients. J Med Genet. 55(1):21-7, 2018
Baertling F et al: The many faces of paediatric mitochondrial disease on neuroimaging. Childs Nerv Syst. 32(11):2077-83, 2016
Gerards M et al: Leigh syndrome: resolving the clinical and genetic heterogeneity paves the way for treatment options. Mol Genet Metab. 117(3):300-12, 2016
Bindu PS et al: Magnetic resonance imaging correlates of genetically characterized patients with mitochondrial disorders: a study from south India. Mitochondrion. 25:6-16, 2015
Bindu PS et al: Electro-clinical features and magnetic resonance imaging correlates in Menkes disease. Brain Dev. 35(5):398-405, 2013
Lebre AS et al: A common pattern of brain MRI imaging in mitochondrial diseases with complex I deficiency. J Med Genet. 48(1):16-23, 2011
Diogo L et al: Value of brain magnetic resonance imaging in mitochondrial respiratory chain disorders. Pediatr Neurol. 42(3):196-200, 2010
Friedman SD et al: The use of neuroimaging in the diagnosis of mitochondrial disease. Dev Disabil Res Rev. 16(2):129-35, 2010
Kumakura A et al: Diffusion-weighted imaging in preclinical Leigh syndrome. Pediatr Neurol. 41(4):309-11, 2009
Lee HF et al: Leigh syndrome: clinical and neuroimaging follow-up. Pediatr Neurol. 40(2):88-93, 2009
Abe K et al: Comparison of conventional and diffusion-weighted MRI and proton MR spectroscopy in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like events. Neuroradiology. 46(2):113-7, 2004
Rossi A et al: Leigh Syndrome with COX deficiency and SURF1 gene mutations: MR imaging findings. AJNR Am J Neuroradiol. 24(6):1188-91, 2003
Schon EA et al: Neuronal degeneration and mitochondrial dysfunction. J Clin Invest. 111:303-12, 2003
Flemming K et al: MR spectroscopic findings in a case of Alpers-Huttenlocher syndrome. AJNR Am J Neuroradiol. 23(8):1421-3, 2002
Related Anatomy
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Related Differential Diagnoses
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References
Tables
Tables
KEY FACTS
Terminology
Imaging
Pathology
TERMINOLOGY
Abbreviations
Mitochondrial encephalopathies (MEs)
Synonyms
Mitochondrial encephalomyelopathies
Definitions
Genetically based disorders of mitochondrial function resulting in progressive or intermittent brain injury
Leigh syndrome (LS)
a.k.a. subacute necrotizing encephalomyelopathy
Defined by its characteristic clinical and pathologic presentation rather than by specific enzymatic deficiency
Characteristic imaging appearance
Myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS)
Leukoencephalopathy with thalamus and brainstem involvement and high lactate (LTBL)
Leukoencephalopathy with brainstem and spinal cord involvement and high lactate (LBSL)
Mitochondrial neurogastrointestinal encephalopathy (MNGIE): TYMP gene recessive mutation (required for mitochondrial DNA replication)
Mitochondrial dysfunction has been associated with myriad clinical pathologies, ranging from autism to Alzheimer dementia to normal aging
This chapter addresses some of those primarily affecting brain, presenting in childhood, and not covered elsewhere
New mutations and phenotypes are constantly being discovered
Many other metabolic diseases primarily affect mitochondria but are not typically considered ME
Neurodegeneration with brain iron accumulation (NBIA), glutaric aciduria type 1, trichothiodystrophy are examples
Classification
Multiple classification schemes for metabolic diseases of mitochondria have been proposed
Clinical phenotype
Longest recognized syndromes are classified by their clinical/pathologic/radiologic presentation
LS is defined in this manner
Locale of genetic defect
Mutation in mitochondrial DNA (mtDNA) or nuclear DNA (nDNA)
Segment of metabolic pathway affected
Respiratory chain (RC) subunits: Complexes I-V
mtDNA transcription defects: POLG-RD
Pyruvate metabolism disorders: PDH and PC deficiency
All have strengths and weaknesses, reflecting complexity of structure and function of organelle
IMAGING
General Features
CT Findings
MR Findings
Imaging Recommendations
DIFFERENTIAL DIAGNOSIS
PATHOLOGY
General Features
CLINICAL ISSUES
Presentation
Demographics
Natural History & Prognosis
Treatment
DIAGNOSTIC CHECKLIST
Image Interpretation Pearls
Selected References
Shelkowitz E et al: Serial magnetic resonance imaging (MRI) in pyruvate dehydrogenase complex deficiency. J Child Neurol. 35(2):137-45, 2020
Gramegna LL et al: Cerebral mitochondrial microangiopathy leads to leukoencephalopathy in mitochondrial neurogastrointestinal encephalopathy. AJNR Am J Neuroradiol. 39(3):427-34, 2018
Sofou K et al: Phenotype-genotype correlations in Leigh syndrome: new insights from a multicentre study of 96 patients. J Med Genet. 55(1):21-7, 2018
Baertling F et al: The many faces of paediatric mitochondrial disease on neuroimaging. Childs Nerv Syst. 32(11):2077-83, 2016
Gerards M et al: Leigh syndrome: resolving the clinical and genetic heterogeneity paves the way for treatment options. Mol Genet Metab. 117(3):300-12, 2016
Bindu PS et al: Magnetic resonance imaging correlates of genetically characterized patients with mitochondrial disorders: a study from south India. Mitochondrion. 25:6-16, 2015
Bindu PS et al: Electro-clinical features and magnetic resonance imaging correlates in Menkes disease. Brain Dev. 35(5):398-405, 2013
Lebre AS et al: A common pattern of brain MRI imaging in mitochondrial diseases with complex I deficiency. J Med Genet. 48(1):16-23, 2011
Diogo L et al: Value of brain magnetic resonance imaging in mitochondrial respiratory chain disorders. Pediatr Neurol. 42(3):196-200, 2010
Friedman SD et al: The use of neuroimaging in the diagnosis of mitochondrial disease. Dev Disabil Res Rev. 16(2):129-35, 2010
Kumakura A et al: Diffusion-weighted imaging in preclinical Leigh syndrome. Pediatr Neurol. 41(4):309-11, 2009
Lee HF et al: Leigh syndrome: clinical and neuroimaging follow-up. Pediatr Neurol. 40(2):88-93, 2009
Abe K et al: Comparison of conventional and diffusion-weighted MRI and proton MR spectroscopy in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like events. Neuroradiology. 46(2):113-7, 2004
Rossi A et al: Leigh Syndrome with COX deficiency and SURF1 gene mutations: MR imaging findings. AJNR Am J Neuroradiol. 24(6):1188-91, 2003
Schon EA et al: Neuronal degeneration and mitochondrial dysfunction. J Clin Invest. 111:303-12, 2003
Flemming K et al: MR spectroscopic findings in a case of Alpers-Huttenlocher syndrome. AJNR Am J Neuroradiol. 23(8):1421-3, 2002
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