Clinical, Imaging and Histopathological Features of Adult Onset Leukoencephalopathy with Neuroaxonal Spheroids and Pigmented Glia: A Report of 4 Cases (P02.149)

Abstract

Objective: To report on a series of 4 patients with Adult onset Leukoencephalopathy with Neuroaxonal Spheroids and Pigmented glia (ALSP). Background ALSP is a rare adult onset leukodystrophy, encompassing hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) and pigmentary orthochromatic leukodystrophy (POLD), which had previously been considered separate entities. Design/Methods: Retrospective chart review. Results: Four previously healthy women presented with a rapidly progressive neurological disorder with insidious onset at age 39, 37, 40, and 30 respectively, and were initially diagnosed as multiple sclerosis (MS). One patient had a sister who was diagnosed with MS and died 18 months later, and another had multiple female family members spanning four generations that died soon after being diagnosed with MS or dementia. The other 2 did not have a family history. The clinical courses of the 4 patients were stereotypical with progressive spastic quadriparesis and progressive neurological decline. The major features seen on brain MRI included diffuse cerebral atrophy with corpus callosal atrophy evident at an early stage, diffuse T2 hyperintensities in the subcortical and periventricular white matter with no gadolinium enhancing lesions, and involvement of pyramidal tracts from motor cortex to the brainstem in two patients who had late stage MRIs. Cerebrospinal fluid was normal in all cases. The correct diagnosis of ALSP was established by biopsy (2 cases) and autopsy (2 cases). Histopathology showed the presence of neuroaxonal spheroids in all cases and pigmented glia in two. Conclusions: ALSP may be suspected in adults with rapid to subacute progression of neurological disease, when (i) MRI shows corpus callosal atrophy on a background of generalized brain atrophy, diffuse white matter disease without postcontrast enhancement, (ii) CSF studies are normal, and (iii) studies for systemic inflammatory diseases and specific leukodystrophies are normal. However, despite suggestive MRI changes reported in our series, a brain biopsy remains essential for definitive diagnosis. Disclosure: Dr. Kleinfeld has nothing to disclose. Dr. Mobley has nothing to disclose. Dr. Wegner has nothing to disclose. Dr. Pawate has nothing to disclose.