Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation (LBSL) has recently been defined based on a highly characteristic constellation of abnormalities observed by magnetic resonance imaging and spectroscopy. LBSL is an autosomal recessive disease, most often manifesting in early childhood. Affected individuals develop slowly progressive cerebellar ataxia, spasticity and dorsal column dysfunction, sometimes with a mild cognitive deficit or decline. We performed linkage mapping with microsatellite markers in LBSL families and found a candidate region on chromosome 1, which we narrowed by means of shared haplotypes. Sequencing of genes in this candidate region uncovered mutations in DARS2, which encodes mitochondrial aspartyl-tRNA synthetase, in affected individuals from all 30 families. Enzyme activities of mutant proteins were decreased. We were surprised to find that activities of mitochondrial complexes from fibroblasts and lymphoblasts derived from affected individuals were normal, as determined by different assays.

Recently, a novel leukoencephalopathy syndrome was described in eight patients with a distinct pattern of MRI abnormalities. Here we describe the clinical, laboratory, and MRI findings in five new, unrelated patients. The clinical picture was homogeneous with onset in childhood, a slowly progressive course, variable mental deficits, signs of pyramidal and cerebellar dysfunction and sometimes dorsal column dysfunction. In two patients, a minor head trauma was followed by neurological deterioration and fever. No underlying metabolic defect was found. In two patients serum lactate was elevated, but no evidence of a mitochondrial defect was found. MRI showed variably extensive, diffuse, or spotty cerebral white matter abnormalities and a selective involvement of particular brainstem tracts. The tracts involved included the pyramidal tracts, sensory tracts, superior and inferior cerebellar peduncles, and intraparenchymal trajectories of the trigeminal nerve. In four patients spinal MRI was performed and revealed involvement of tracts over the entire length depicted. Single voxel proton MRS in three patients revealed increased lactate within the abnormal white matter. The uniform and highly characteristic MRI findings, in combination with the similarities in clinical and MRS findings, provide evidence for a distinct nosological entity.

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Differential diagnosis of incurable and potentially curable neurological diseases is an urgent problem of modern neurology. The authors present a case report of subacute herpes virus myelitis, a rare complication of herpes infection by Varicella-Zoster virus. The differential diagnosis with amyotrophic lateral sclerosis is described.