A clinicopathological and brain MRI study in Egyptian children with mitochondrial disorders

Article type: Research Article

Authors: Selim, Laila A. | Ghaffar, Hadeer A. | Hamdi, Maha M. | Hagras, Amal M. | Nakhla, Gina A. | Kamel, Ahmed M.

Affiliations: Department of Pediatrics Cairo University, Children Hospital, Egypt | Department of Pathology Cairo University, Kasr El Eini Hospital, Egypt | Department of Radiology, Cairo University, Kasr El Eini Hospital, Egypt

Note: [] Correspondence: Laila A. Selim, MD, Department of Pediatrics, Division of Neuropediatrics, Cairo University Children Hospital, Egypt. Tel.: +20 35963650, +20 7509155; E-mail: lailaselim@hotmail.com

Abstract: This prospective study was undertaken to focus on the clinicopathological aspects as well as the value of brain magnetic resonance imaging (MRI) in children suffering from mitochondriopathies. Thirty-one patients [15 males (48.4%) and 16 females (51.6%)] gathered from the neuropediatric and metabolic clinic of Cairo University Children Hospital were included in this study. All patients were subjected to a thorough history and a meticulous clinical examination, computerized tomography and (MRI), electromyography and nerve conduction velocity. Muscle biopsies were performed in 18/31 patients and were subjected to both cytochrome c oxidase (COX) staining and electron microscopic (EM) examination. Laboratory tests including serum lactate and pyruvate, serum creatine kinase (CK), urine and plasma aminogram, urine organic acid profile, acyl carnitine profile, enzymatic analysis for arylsulfatase, galactocerebrosidase, very long chain fatty acids, acetyl aspartase were also performed when needed. Patients were classified according to their clinical phenotypes into: mitochondrial leukoencephalopathy (3/31), Leigh syndrome (7/31), neuropathy, ataxia and retinitis pigmentosa (2/31), mitochondrial encephalomyopathy (6/31), Leber's hereditary opticneuropathy (4/31), mitochondrial encephalopathy, red ragged fibers (MERRF) (1/31). Mitochondrial encephalopathy, lactic acidosis (MELAS) (1/31), familial dystonia (4/31), and mitochondrial myopathy (3/31). The main neurological manifestations in their order of frequency were global developmental delay (20; 64.5%), spasticity (16; 51.6%), hypotonia (12; 38.7%), convulsions (10; 32.3%), sensory neural deafness (7; 22.6%), dystonia (7; 22.6%) optic atrophy (5; 16.1%), proximal muscle weakness (3; 9.7%), retinitis pigmentosa (2; 6.5%) and ataxia (2; 6.5%). Electromyography and nerve conduction study were normal in 18/31 (58%), myopathic in 7/31 (22.6%) and neuropathic in 6/31 (19.4%) patients. CK was significantly increased in only 3/31 (9.7%) patients. The main MRI findings were basal ganglia abnormalities appearing as bilateral and symmetrical high signal intensity lesions on T2 weighted MRI (11/28; 39.3%). Magnetic resonance spectroscopy (MRS) was performed in 7 patients and all were showing an increase lactate peak. EM examination revealed a subsarcolemmal aggregation of mitochondria in (12/18; 66.7%) and or a large and bizarre shaped mitochondria in (8/18; 44.4%), nonspecific myopathic changes in (3/18; 16.7%). Histochemical analysis of muscle biopsies using COX staining revealed a COX- vein (5/11; 45.5%), COX +vein (6/11; 54.5%), and myopathic changes in (3/18; 16.7%) patients. In conclusion, MRI and MRS are proved a promising tool in the diagnosis of mitochondrial cytopathies. MRS is a sensitive, non-invasive tool to evaluate the pathological lactate production in metabolic brain disease with disturbed energy production.

Keywords: Mitochondrial cytopathies, brain MRI, MRS, muscle biopsy, cytochrome c oxidase, electron microscopy

Journal: Journal of Pediatric Neurology, vol. 3, no. 4, pp. 207-215, 2005