Progressive Neuropsychiatric Symptoms and Motor Impairment

Abstract

Insights into the dynamics of hereditary diffuse leukoencephalopathy with axonal spheroids. Neurology. 2008;71(12): 925-929. 23. Keegan BM, Giannini C, Parisi JE, Lucchinetti CF, Boeve BF, Josephs KA. Sporadic adult-onset leukoencephalopathy with neuroaxonal spheroids mimicking cerebral MS.

Mendelian adult-onset leukodystrophy genes in Alzheimer's disease: critical influence of CSF1R and NOTCH3

“…Second, T2-weighted MRI, available for 2 patients, showed symmetric patchy periventricular hyperintensities, mainly pronounced in the frontal lobe (patient E) and bilateral lesions localized to the centrum semiovale (patient F) ( Fig. 4 B), that represent common MRI findings in HDLS patients ( Ghadiri et al., 2014 ), ( Rademakers et al., 2011 ) ( Boissé et al., 2010 ) ( Mateen et al., 2010 ). Finally, senile plaques, amyloid angiopathy, and tau tangles have been reported also in the cortex and hippocampus of 2 familial and 1 sporadic HDLS patients ( Baba et al., 2006 ) ( Browne et al., 2003 ).…”

“…In our discovery and validation cohorts, we detected 3 rare coding variants in the TK domain of CSF1R in 3 LOAD cases, one of these neuropathologically confirmed. Moreover, we report 2 cases harboring rare mutations in the TK flanking regions (aa 538–580 and aa 911–972, encoded by exon 12 and 22, respectively), where an additional causative mutation for HDLS has been recently described (c.1736G>A, p.R579Q) ( Ghadiri et al., 2014 ). These variants are very likely pathogenic: they cluster to highly conserved domains among different species (average PhyloP and PhastCons scores = 2.2 and 0.6, respectively) ( Fig.…”