Bookmarks
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 & pathologic presentation rather than by specific enzymatic deficiency
- Characteristic imaging appearance
- Myopathy, encephalopathy, lactic acidosis, & stroke-like episodes (MELAS)
- Kearns-Sayre syndrome (KSS)
- DNA polymerase γ-related disorders (POLG-RD)
- Disorders of pyruvate metabolism
- Pyruvate dehydrogenase (PDH) deficiency
- Pyruvate carboxylase (PC) deficiency
- Mitochondrial aminoacyl tRNA synthetase deficiencies
- Leukoencephalopathy with thalamus & brainstem involvement & high lactate (LTBL)
- Leukoencephalopathy with brainstem & spinal cord involvement & high lactate (LBSL)
- Leigh syndrome (LS)
- Mitochondrial dysfunction has been associated with myriad clinical pathologies, ranging from autism to Alzheimer dementia to normal aging
- This document addresses some of those primarily affecting brain, presenting in childhood, & not covered elsewhere
- New mutations & phenotypes are constantly being discovered
- This document addresses some of those primarily affecting brain, presenting in childhood, & not covered elsewhere
- 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
- Genetically based disorders of mitochondrial function resulting in progressive or intermittent brain injury
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
- Longest recognized syndromes are classified by their clinical/pathologic/radiologic presentation
- 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 & PC deficiency
- Clinical phenotype
- All classifications have strengths & weaknesses, reflecting complexity of structure & function of organelle
- Multiple classification schemes for metabolic diseases of mitochondria have been proposed
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
- Gonçalves FG et al: Primary mitochondrial disorders of the pediatric central nervous system: neuroimaging findings. Radiographics. 40(7):2042-67, 2020
- Mohammad SS et al: Magnetic resonance imaging pattern recognition in childhood bilateral basal ganglia disorders. Brain Commun. 2(2):fcaa178, 2020
- Alves CAPF et al: Neuroimaging of mitochondrial cytopathies. Top Magn Reson Imaging. 27(4):219-40, 2018
- Finsterer J et al: Cerebral imaging in paediatric mitochondrial disorders. Neuroradiol J. 31(6):596-608, 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
Loading...
Related Differential Diagnoses
Loading...
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 & pathologic presentation rather than by specific enzymatic deficiency
- Characteristic imaging appearance
- Myopathy, encephalopathy, lactic acidosis, & stroke-like episodes (MELAS)
- Kearns-Sayre syndrome (KSS)
- DNA polymerase γ-related disorders (POLG-RD)
- Disorders of pyruvate metabolism
- Pyruvate dehydrogenase (PDH) deficiency
- Pyruvate carboxylase (PC) deficiency
- Mitochondrial aminoacyl tRNA synthetase deficiencies
- Leukoencephalopathy with thalamus & brainstem involvement & high lactate (LTBL)
- Leukoencephalopathy with brainstem & spinal cord involvement & high lactate (LBSL)
- Leigh syndrome (LS)
- Mitochondrial dysfunction has been associated with myriad clinical pathologies, ranging from autism to Alzheimer dementia to normal aging
- This document addresses some of those primarily affecting brain, presenting in childhood, & not covered elsewhere
- New mutations & phenotypes are constantly being discovered
- This document addresses some of those primarily affecting brain, presenting in childhood, & not covered elsewhere
- 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
- Genetically based disorders of mitochondrial function resulting in progressive or intermittent brain injury
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
- Longest recognized syndromes are classified by their clinical/pathologic/radiologic presentation
- 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 & PC deficiency
- Clinical phenotype
- All classifications have strengths & weaknesses, reflecting complexity of structure & function of organelle
- Multiple classification schemes for metabolic diseases of mitochondria have been proposed
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
- Gonçalves FG et al: Primary mitochondrial disorders of the pediatric central nervous system: neuroimaging findings. Radiographics. 40(7):2042-67, 2020
- Mohammad SS et al: Magnetic resonance imaging pattern recognition in childhood bilateral basal ganglia disorders. Brain Commun. 2(2):fcaa178, 2020
- Alves CAPF et al: Neuroimaging of mitochondrial cytopathies. Top Magn Reson Imaging. 27(4):219-40, 2018
- Finsterer J et al: Cerebral imaging in paediatric mitochondrial disorders. Neuroradiol J. 31(6):596-608, 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
