Involvement of the Spinal Cord in Mitochondrial Disorders

Abstract

This review aims at summarising and discussing the current status concerning the clinical presentation, pathogenesis, diagnosis, and treatment of spinal cord affection in mitochondrial disorders (MIDs). A literature search using the database Pubmed was carried out by application of appropriate search terms and their combinations. Involvement of the spinal cord in MIDs is more frequent than anticipated. It occurs in specific and non-specific MIDs. Among the specific MIDs it has been most frequently described in LBSL, LS, MERRF, KSS, IOSCA, MIRAS, and PCH and only rarely in MELAS, CPEO, and LHON. Clinically, spinal cord involvement manifests as monoparesis, paraparesis, quadruparesis, sensory disturbances, hypotonia, spasticity, urinary or defecation dysfunction, spinal column deformities, or as transverse syndrome. Diagnosing spinal cord involvement in MIDs requires a thoroughly taken history, clinical exam, and imaging studies. Additionally, transcranial magnetic stimulation, somato-sensory-evoked potentials, and cerebro-spinal fluid can be supportive. Treatment is generally not at variance compared to the underlying MID but occasionally surgical stabilisation of the spinal column may be necessary. It is concluded that spinal cord involvement in MIDs is more frequent than anticipated but may be missed if cerebral manifestations prevail. Spinal cord involvement in MIDs may strongly determine the mobility of these patients.

Spinal cord involvement in Kearns-Sayre syndrome: a neuroimaging study

“…These findings support the potential involvement of the spinal cord in mitochondrial disorders, such as LBSL (leukoencephalopathy with the brainstem, spinal cord involvement, and lactate elevation) syndrome due to DARS2 mutation where the posterior white matter columns are predominately involved [4,20,21]. However, as observed in our patients with KSS, the disease may also extend to other regions [6,22]. Pathologic analysis of demyelinated areas from spinal nerve roots in KSS described the presence of glial bundles [16], an unspecific finding shared by multiple conditions, including degenerative and inflammatory disorders [23,24].…”

“…Later, autoptic reports confirmed this evidence, supporting the idea of spinal cord lesions being more common than previously thought. In fact, other mitochondrial leukodystrophies show variable spinal cord involvement, supporting the possibility of similar findings for KSS [6].…”

“…Our findings in vivo support these observations. Compared with previous reports [6], in the population included in the study, spinal cord involvement was not limited to the cervical segment but often (4 cases) involved the thoracic and lumbar segment with a more extended pattern of injury. On the axial plane, we identified four radiological patterns of spinal disease: exclusive gray matter ("H" pattern), gray matter and white matter of the posterior columns ("H" plus pattern), exclusive posterior columns (posterior pattern), or anterior columns (anterior pattern) ( Fig.…”

ISCA2 mutations manifest differentially from DARS2 mutations

“…The spinal cord may not only be involved in patients with LBSL or patients carrying a ISAC2 mutation (Finsterer and Zarrouk-Mahjoub 2018). Among the specific MIDs spinal cord involvement has been additionally described in Leighsyndrome, MERRF, KSS, IOSCA, MIRAS, PCH6, MELAS, CPEO, and LHON (Finsterer and Zarrouk-Mahjoub 2018).…”

“…The spinal cord may not only be involved in patients with LBSL or patients carrying a ISAC2 mutation (Finsterer and Zarrouk-Mahjoub 2018). Among the specific MIDs spinal cord involvement has been additionally described in Leighsyndrome, MERRF, KSS, IOSCA, MIRAS, PCH6, MELAS, CPEO, and LHON (Finsterer and Zarrouk-Mahjoub 2018). Additionally, non-specific MIDs due to mutations in SURF1, tRNA(Glu), or POLG1, may present with spinal cord involvement (Finsterer and Zarrouk-Mahjoub 2018).…”