Early Spinal Cord and Brainstem Involvement in Infantile Leigh Syndrome Possibly Caused by a Novel Variant

Abstract

Leigh syndrome, due to a dysfunction of mitochondrial energy metabolism, is a genetically heterogeneous and progressive neurologic disorder that usually occurs in infancy and childhood. Its clinical presentation and neuroimaging findings can be variable, especially early in the course of the disease. This report presents a patient with infantile Leigh syndrome who had atypical radiologic findings on serial neuroimaging studies with early and severe involvement of the cervical spinal cord and brainstem and injury to the thalami and basal ganglia occurring only late in the clinical course. Postmortem microscopic examination supported this timing of injury within the central nervous system. In addition, mitochondrial deoxyribonucleic acid sequencing showed a novel homoplasmic variant that could be responsible for this unique lethal form of Leigh syndrome.

Involvement of the Spinal Cord in Mitochondrial Disorders

“…In some cases, spinal cord affection may be the initial manifestation of a MID, as in LS. [ 21 ] Some cases may present with features of a motor neuron disease, thus mimicking spinal muscular atrophy or amyotrophic lateral sclerosis. [ 4 5 ] Rarely, spinal cord involvement may manifest as sensory or motor transverse syndrome.…”

“…[ 3 ] In a 6-month-old Hispanic male with early-onset LS, involvement of the cervical spinal cord and brainstem were responsible for the initial clinical presentation. [ 21 ] At age 2 months, the cerebral MRI was normal. Repeat MRI of the cerebrum and the cervical spine at age 3.5 months showed abnormal signal intensity and restricted diffusion involving the brainstem (pons and medulla) and upper cervical spinal cord.…”

“…Repeat MRI of the cerebrum and the cervical spine at age 3.5 months showed abnormal signal intensity and restricted diffusion involving the brainstem (pons and medulla) and upper cervical spinal cord. [ 21 ] In a 3-year-old female with the clinical diagnosis of LS who died suddenly and unexplained, autopsy showed symmetrical, necrotizing lesions scattered within the spinal cord's gray matter. [ 22 ] In a series of 5 children with LS, isolated affection of the spinal cord without brain abnormalities was described in a 17-month-old female at autopsy.…”

Spatiotemporal mapping of interictal epileptiform discharges in human absence epilepsy: A MEG study

“…Functional MRI (fMRI) studies confirmed not only a focal cortical driving origin, but also demonstrated that SWDs propagate to distinct cortical regions (Aghakhani et al, 2004;Blumenfeld, 2007;Carney et al, 2010;David et al, 2008;Gotman et al, 2005;Moeller et al, 2013a; http://dx.doi.org/10.1016/j.eplepsyres.2015.11.013 0920-1211/© 2015 Elsevier B.V. All rights reserved. Tenney et al, 2013). In addition, high-resolution EEG and MEG studies in children and adults with various types of absence seizures in combination with advanced signal analytical techniques have confirmed the existence of a preferential cortical origin of SWDs.…”

“…In addition, high-resolution EEG and MEG studies in children and adults with various types of absence seizures in combination with advanced signal analytical techniques have confirmed the existence of a preferential cortical origin of SWDs. Focal cortical regions with increased connectivity were detected either in the frontal cortex, orbito-frontal, medial temporal or parietal lobe (Amor et al, 2009;Holmes et al, 2004;Tenney et al, 2013;Westmijse et al, 2009). It is obvious that this challenges the dichotomy between focal and generalized epilepsy.…”