Parayil Sankaran Bindu1, Kothari Sonam2, Shwetha Chiplunkar2, Periyasamy Govindaraj1, Madhu Nagappa1, Chetan Chandrakanth Vekhande3, Hanumanthapura R Aravinda4, Jn Jessiena Ponmalar5, Anita Mahadevan6, Narayanappa Gayathri6, Mm Srinivas Bharath7, Sanjib Sinha3, Arun B Taly8. 1. Departments of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India; Neuromuscular Lab, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India. 2. Clinical Neurosciences, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India; Neuromuscular Lab, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India. 3. Departments of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India. 4. Neuroimaging and Interventional Radiology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India. 5. Neuromuscular Lab, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India. 6. Neuropathology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India; Neuromuscular Lab, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India. 7. Neurochemistry, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India. 8. Departments of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India; Neuromuscular Lab, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India. Electronic address: abtaly@yahoo.com.
Abstract
BACKGROUND: There is emerging evidence implicating mitochondrial dysfunction in the pathogenesis of acquired demyelinating disorders such as multiple sclerosis. On the other hand, some of the primary mitochondrial disorders such as mitochondrial leukoencephalopathies exhibit evidence of neuroinflammation on MRI. The inter-relationship between mitochondrial disorders and episodic CNS inflammation needs exploration because of the therapeutic implications. OBJECTIVE: We sought to analyze the clinical course and MRI characteristics in a cohort of patients with mitochondrial leukoencephalopathy to determine features, if any, that mimic primary demyelinating disorders. Therapeutic implications of these findings are discussed. PATIENTS AND METHODS: Detailed analysis of the clinical course, magnetic resonance imaging findings and therapeutic response was performed in 14 patients with mitochondrial leukoencephalopathy. The diagnosis was ascertained by clinical features, histopathology, respiratory chain enzyme assays and exome sequencing. RESULTS: Fourteen patients [Age at evaluation: 2-7 yrs, M: F-1:1] were included in the study. The genetic findings included variations in NDUFA1 (1); NDUFV1 (4); NDUFS2 (2); LYRM (2);MPV17(1); BOLA3(2); IBA57(2). Clinical Features which mimicked acquired demyelinating disorder included acute onset focal deficits associated with encephalopathy [10/14, 71%], febrile illness preceding the onset [7/14, 50%] unequivocal partial or complete steroid responsiveness [11/11], episodic/ relapsing remitting neurological dysfunction [10/14, 71%] and a subsequent stable rather than a progressive course [12/14, 85%]. MRI characteristics included confluent white matter lesions [14/14, 100%], diffusion restriction [11/14,78.5%], contrast enhancement [13/13,100%], spinal cord involvement [8/13,61.5%], lactate peak on MRS [13/13] and white matter cysts [13/14, 92.8%]. CONCLUSION: Clinical presentations of mitochondrial leukoencephalopathy often mimic an acquired demyelinating disorder. The therapeutic implications of these observations require further exploration.
BACKGROUND: There is emerging evidence implicating mitochondrial dysfunction in the pathogenesis of acquired demyelinating disorders such as multiple sclerosis. On the other hand, some of the primary mitochondrial disorders such as mitochondrial leukoencephalopathies exhibit evidence of neuroinflammation on MRI. The inter-relationship between mitochondrial disorders and episodic CNS inflammation needs exploration because of the therapeutic implications. OBJECTIVE: We sought to analyze the clinical course and MRI characteristics in a cohort of patients with mitochondrial leukoencephalopathy to determine features, if any, that mimic primary demyelinating disorders. Therapeutic implications of these findings are discussed. PATIENTS AND METHODS: Detailed analysis of the clinical course, magnetic resonance imaging findings and therapeutic response was performed in 14 patients with mitochondrial leukoencephalopathy. The diagnosis was ascertained by clinical features, histopathology, respiratory chain enzyme assays and exome sequencing. RESULTS: Fourteen patients [Age at evaluation: 2-7 yrs, M: F-1:1] were included in the study. The genetic findings included variations in NDUFA1 (1); NDUFV1 (4); NDUFS2 (2); LYRM (2);MPV17(1); BOLA3(2); IBA57(2). Clinical Features which mimicked acquired demyelinating disorder included acute onset focal deficits associated with encephalopathy [10/14, 71%], febrile illness preceding the onset [7/14, 50%] unequivocal partial or complete steroid responsiveness [11/11], episodic/ relapsing remitting neurological dysfunction [10/14, 71%] and a subsequent stable rather than a progressive course [12/14, 85%]. MRI characteristics included confluent white matter lesions [14/14, 100%], diffusion restriction [11/14,78.5%], contrast enhancement [13/13,100%], spinal cord involvement [8/13,61.5%], lactate peak on MRS [13/13] and white matter cysts [13/14, 92.8%]. CONCLUSION: Clinical presentations of mitochondrial leukoencephalopathy often mimic an acquired demyelinating disorder. The therapeutic implications of these observations require further exploration.
Authors: Marisa W Friederich; Francisco A Perez; Kaz M Knight; Roxanne A Van Hove; Samuel P Yang; Russell P Saneto; Johan L K Van Hove Journal: Mol Genet Metab Date: 2019-12-30 Impact factor: 4.797
Authors: Quynh-Chi L Dang; Duong H Phan; Abigail N Johnson; Mukund Pasapuleti; Hind A Alkhaldi; Fang Zhang; Steven B Vik Journal: Life (Basel) Date: 2020-11-20