Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (LBSL): assessment of the involved white matter tracts by MRI.

BACKGROUND AND PURPOSE: Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation (LBSL) is a recently identified autosomal recessive disorder with early onset of symptoms and slowly progressive pyramidal, cerebellar and dorsal column dysfunction. LBSL is characterized by distinct white matter abnormalities and selective involvement of brainstem and spinal cord tracts. The purpose of this study is to assess the imaging features of the involved white matter tracts in cases of LBSL by MRI. PATIENTS AND METHODS: We retrospectively reviewed the imaging features of the selectively involved white matter tracts in sixteen genetically proven cases of leukoencephalopathy with brainstem and spinal cord involvement and elevated brain lactate (LBSL). All patients presented with slowly progressive cerebellar sensory ataxia with spasticity and dorsal column dysfunction. MRI of the brain and spine using 1.5 T machine and proton magnetic resonance spectroscopy (1H MRS) on the abnormal white matter were done to all patients. The MRI and MRS data sets were analyzed according to lesion location, extent, distribution and signal pattern as well as metabolite values and ratios in MRS. Laboratory examinations ruled out classic leukodystrophies. RESULTS: In all cases, MRI showed high signal intensity in T2-weighted and FLAIR images within the cerebral subcortical, periventricular and deep white matter, posterior limbs of internal capsules, centrum semiovale, medulla oblongata, intraparenchymal trajectory of trigeminal nerves and deep cerebellar white matter. In the spine, the signal intensity of the dorsal column and lateral cortico-spinal tracts were altered in all patients. The subcortical U fibers, globi pallidi, thalami, midbrain and transverse pontine fibers were spared in all cases. In 11 cases (68.8%), the signal changes were inhomogeneous and confluent whereas in 5 patients (31.2%), the signal abnormalities were spotty. MRI also showed variable signal abnormalities in the sensory and pyramidal tracts in addition to the brainstem and cerebellar connections. Proton MRS showed consistent elevation of the lactate within the abnormal white matter. CONCLUSION: Distinct MRI findings in the form of selective affection of subcortical and deep white matter tracts of the brain (involving the posterior limb of internal capsules and sparing the subcortical U fibers), dorsal column and lateral cortico-spinal tracts of the spinal cord should lead to the diagnosis of LBSL supported by the presence of lactate peak in 1H MRS. The disease can be confirmed by the analysis of the disease gene DARS2.

Case control series of intrathecal autologous bone marrow mesenchymal stem cell therapy for chronic spinal cord injury.

BACKGROUND: Autologous bone marrow mesenchymal cells that include stem cells (MSCs) are a clinically attractive cellular therapy option to try to treat severe spinal cord injury (SCI). OBJECTIVE: To study the possible value of MSCs injected intrathecally to enhance rehabilitation. METHODS: This case control, convenience sample included 64 patients, at a mean of 3.6 years after SCI. Forty-four subjects received monthly intrathecal autologous MSCs for 6 months and 20 subjects, who would not agree to the procedures, served as controls. All subjects received rehabilitation therapies 3 times weekly. Subjects were evaluated at entry and at 12 months after completing the 6-months intervention. By the ASIA Impairment Scale, ASIA grading of completeness of injury, Ashworth Spasticity Scale, Functional Ambulation Classification, and bladder and bowel control questionnaire. RESULTS: No differences were found in baseline measures and descriptors between the MSC group and control group. Although a higher percentage of the MSC group increased motor scores by 1-2 points and changed from ASIA A to B, no significant between-group improvements were found in clinical measures. Adverse effects of cells included spasticity and, in 24 out of the 43 patients developed neuropathic pain. One subject with a history of post-infectious myelitis developed encephalomyelitis after her third injection. CONCLUSION: Autologus MSCs may have side effects and may be contraindicated in patients with a history of myelitis. Their utility in treating chronic traumatic SCI needs further study in pre-clinical models and in randomized controlled trials before they should be offered to patients.