Neurocognitive Decline and Motor Regression in a 34-Year-Old Woman

Sumaira Nabi, MBBS; Zakir Jan, MBBS, FCPS Neurology; Muhammad Irshad, MBBS, FCPS Neurology


April 23, 2018

Due to its high sensitivity, MRI of the brain is the primary neuroimaging strategy used for the diagnosis of MLD, detection of the extent and etiology of white-matter involvement, and monitoring of the disease's progression.[11] Some leukodystrophies like MLD have typical MRI patterns. Brain MRI reveals demyelination, predominantly within the centrum semiovale.[12,13] The demyelination is most severe in the periventricular white matter, diminishing in regions closer to the cortex. The subcortical U fibers tend to be spared early in the course of the disease. Variable degrees of cerebral atrophy may be present. The prevalent region of demyelination in the late-onset group is a posterior one involving the occipital lobes more than the frontal lobes, as seen in this patient.[14] MR spectroscopy reveals reduced N-acetylaspartate, increased myoinositol, and increased lactate.[11]

In addition to the MRI changes, typical histopathologic findings can be demonstrated on biopsy of a peripheral nerve. Metachromatic granules are found within glial cells and macrophages.[4] In addition, sulfatides are also periodic acid-Schiff (PAS) positive in frozen section. The diagnostic laboratory findings include elevated CSF protein, marked increase in sulfatide in urine levels,[15] and an absence of arylsulfatase A in white blood cells, serum, and cultured fibroblasts.[1,5] In this patient, due to unavailability, tests to assess her enzyme and urine sulfatide levels were not performed.

MLD is currently considered to be incurable. Hematopoietic stem cell transplantation, gene therapy and enzyme replacement therapy have shown positive results in animal models and have been investigated in clinical trials. The benefit of hematopoietic stem cell/bone marrow transplantation has not been consistently demonstrated or shown to be sustained. This is likely related to the rapid progression of the disease. A presymptomatic or early symptomatic individual is the most appropriate candidate.[16,17,18,19,20,21,22,23] Restoration of arylsulfatase A activity via retroviral vector-mediated gene transfer is also being investigated. Little is known about the symptomatic treatment of psychotic symptoms and dementia in MLD, although atypical antipsychotics have been tried for the psychotic features.[4]

This case highlights an organic disease as a cause of what initially appeared to be a fairly straightforward case of schizophrenia. It demonstrates that, in cases of psychosis with associated cognitive decline and motor deterioration, an organic cause must be ruled out.


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