Spinal cord involvement in adult-onset metabolic and genetic diseases

Abstract

In adulthood, spinal cord MRI abnormalities such as T2-weighted hyperintensities and atrophy are commonly associated with a large variety of causes (inflammation, infections, neoplasms, vascular and spondylotic diseases). Occasionally, they can be due to rare metabolic or genetic diseases, in which the spinal cord involvement can be a prominent or even predominant feature, or a secondary one. This review focuses on these rare diseases and associated spinal cord abnormalities, which can provide important but over-ridden clues for the diagnosis. The review was based on a PubMed search (search terms: 'spinal cord' AND 'leukoencephalopathy' OR 'leukodystrophy'; 'spinal cord' AND 'vitamin'), further integrated according to the authors' personal experience and knowledge. The genetic and metabolic diseases of adulthood causing spinal cord signal alterations were identified and classified into four groups: (1) leukodystrophies; (2) deficiency-related metabolic diseases; (3) genetic and acquired toxic/metabolic causes; and (4) mitochondrial diseases. A number of genetic and metabolic diseases of adulthood causing spinal cord atrophy without signal alterations were also identified. Finally, a classification based on spinal MRI findings is presented, as well as indications about the diagnostic work-up and differential diagnosis. Some of these diseases are potentially treatable (especially if promptly recognised), while others are inherited as autosomal dominant trait. Therefore, a timely diagnosis is needed for a timely therapy and genetic counselling. In addition, spinal cord may be the main site of pathology in many of these diseases, suggesting a tempting role for spinal cord abnormalities as surrogate MRI biomarkers.

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].…”

“…Despite multiple reports of brain involvement on MRI in the literature, spinal cord disease is poorly described on imaging, and spine MRI evaluation is seldom performed in the clinical routine of patients affected by KSS [4]. Kearns and Sayre described cervical spinal cord involvement in their first post-mortem autoptic report of the disease, attributing the finding to possible post-mortem artifacts [5].…”

Hereditary spastic paraplegia: from diagnosis to emerging therapeutic approaches

“…Other rare genetic and metabolic causes associated with T2-weighted abnormalities in the spinal cord were recently reviewed by Marelli and colleagues. 39 MRI of the brain can help differentiate SPG types, although there are very few pathognomonic changes. Cerebellar atrophy is seen in 39-95% of SPG7 cases, mostly as mild atrophy of the cerebellar vermis (figure 1), 23,25 however this has also been reported other rarer HSPs.…”

Cross sign T2 hyperintensities in atrophic spinal cord of hereditary spastic paraplegia type 5

“…T2 hyperintensities in spinal cord MRI are commonly associated with a large variety of causes (in ammation, infections, neoplasms, vascular, and spondylotic diseases), but it is rarely caused by HSP, except as reported for hereditary spastic paraplegias type 2 (SPG2), due to PLP1 gene mutations (13).…”