link
Bookmarks
Mitochondrial Encephalopathies
Blaise V. Jones, MD; Surjith Vattoth, MD, FRCR
To access 4,300 diagnoses written by the world's leading experts in radiology, please log in or subscribe.Log inSubscribe
0
12
2
0

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)
            • 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 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

                              1. Shelkowitz E et al: Serial magnetic resonance imaging (MRI) in pyruvate dehydrogenase complex deficiency. J Child Neurol. 35(2):137-45, 2020
                              2. Gramegna LL et al: Cerebral mitochondrial microangiopathy leads to leukoencephalopathy in mitochondrial neurogastrointestinal encephalopathy. AJNR Am J Neuroradiol. 39(3):427-34, 2018
                              3. 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
                              4. Baertling F et al: The many faces of paediatric mitochondrial disease on neuroimaging. Childs Nerv Syst. 32(11):2077-83, 2016
                              5. 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
                              6. 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
                              7. Bindu PS et al: Electro-clinical features and magnetic resonance imaging correlates in Menkes disease. Brain Dev. 35(5):398-405, 2013
                              8. 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
                              9. Diogo L et al: Value of brain magnetic resonance imaging in mitochondrial respiratory chain disorders. Pediatr Neurol. 42(3):196-200, 2010
                              10. Friedman SD et al: The use of neuroimaging in the diagnosis of mitochondrial disease. Dev Disabil Res Rev. 16(2):129-35, 2010
                              11. Kumakura A et al: Diffusion-weighted imaging in preclinical Leigh syndrome. Pediatr Neurol. 41(4):309-11, 2009
                              12. Lee HF et al: Leigh syndrome: clinical and neuroimaging follow-up. Pediatr Neurol. 40(2):88-93, 2009
                              13. 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
                              14. 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
                              15. Schon EA et al: Neuronal degeneration and mitochondrial dysfunction. J Clin Invest. 111:303-12, 2003
                              16. 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 and pathologic presentation rather than by specific enzymatic deficiency
                                            • Characteristic imaging appearance
                                        • Myopathy, encephalopathy, lactic acidosis, and 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 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

                                                          1. Shelkowitz E et al: Serial magnetic resonance imaging (MRI) in pyruvate dehydrogenase complex deficiency. J Child Neurol. 35(2):137-45, 2020
                                                          2. Gramegna LL et al: Cerebral mitochondrial microangiopathy leads to leukoencephalopathy in mitochondrial neurogastrointestinal encephalopathy. AJNR Am J Neuroradiol. 39(3):427-34, 2018
                                                          3. 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
                                                          4. Baertling F et al: The many faces of paediatric mitochondrial disease on neuroimaging. Childs Nerv Syst. 32(11):2077-83, 2016
                                                          5. 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
                                                          6. 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
                                                          7. Bindu PS et al: Electro-clinical features and magnetic resonance imaging correlates in Menkes disease. Brain Dev. 35(5):398-405, 2013
                                                          8. 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
                                                          9. Diogo L et al: Value of brain magnetic resonance imaging in mitochondrial respiratory chain disorders. Pediatr Neurol. 42(3):196-200, 2010
                                                          10. Friedman SD et al: The use of neuroimaging in the diagnosis of mitochondrial disease. Dev Disabil Res Rev. 16(2):129-35, 2010
                                                          11. Kumakura A et al: Diffusion-weighted imaging in preclinical Leigh syndrome. Pediatr Neurol. 41(4):309-11, 2009
                                                          12. Lee HF et al: Leigh syndrome: clinical and neuroimaging follow-up. Pediatr Neurol. 40(2):88-93, 2009
                                                          13. 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
                                                          14. 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
                                                          15. Schon EA et al: Neuronal degeneration and mitochondrial dysfunction. J Clin Invest. 111:303-12, 2003
                                                          16. Flemming K et al: MR spectroscopic findings in a case of Alpers-Huttenlocher syndrome. AJNR Am J Neuroradiol. 23(8):1421-3, 2002