Sporadic adult-onset leukoencephalopathy with neuroaxonal spheroids mimicking cerebral MS

Keegan, B. Mark; Giannini, Caterina; Parisi, Joseph E.; Lucchinetti, C. F.; Boeve, B. F.; Josephs, K.

doi:10.1212/01.wnl.0000304045.99153.8f

Cited by 52 publications

(62 citation statements)

References 22 publications

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“…DISCUSSION Our report describes the MRI pattern of HDLS in patients with CSF1R gene mutations. MRI findings in patients with HDLS have been described previously in 20 reports, 5,[12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] however, without knowledge of the CSF1R gene mutation carrier status. 4 We developed an HDLS MRI severity scoring system, modified from those devised for X-ALD, Krabbe disease, and MLD.…”

Section: Resultsmentioning

confidence: 81%

MRI characteristics and scoring in HDLS due to CSF1R gene mutations

Sundal¹,

Gerpen²,

Nicholson³

et al. 2012

Neurology

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Objective: To describe the brain MRI characteristics of hereditary diffuse leukoencephalopathy with spheroids (HDLS) with known mutations in the colony-stimulating factor 1 receptor gene (CSF1R) on chromosome 5. Methods:We reviewed 20 brain MRI scans of 15 patients with autopsy-or biopsy-verified HDLS and CSF1R mutations. We assessed sagittal T1-, axial T1-, T2-, proton density-weighted and axial fluid-attenuated inversion recovery images for distribution of white matter lesions (WMLs), gray matter involvement, and atrophy. We calculated a severity score based on a point system (0Ϫ57) for each MRI scan. Results:Of the patients, 93% (14 of 15) demonstrated localized WMLs with deep and subcortical involvement, whereas one patient revealed generalized WMLs. All WMLs were bilateral but asymmetric and predominantly frontal. Fourteen patients had a rapidly progressive clinical course with an initial MRI mean total severity score of 16.7 points (range 10Ϫ33.5). Gray matter pathology and brainstem atrophy were absent, and the corticospinal tracts were involved late in the disease course. There was no enhancement, and there was minimal cerebellar pathology. Conclusion:Recognition of the typical MRI patterns of HDLS and the use of an MRI severity score might help during the diagnostic evaluation to characterize the natural history and to monitor potential future treatments. Indicators of rapid disease progression were symptomatic disease onset before 45 years, female sex, WMLs extending beyond the frontal regions, a MRI severity score greater than 15 points, and mutation type of deletion. Neurology ® 2012;79:566-574 GLOSSARY CI ϭ confidence interval; CSF1R ϭ colony-stimulating factor 1 receptor; FLAIR ϭ fluid-attenuated inversion recovery; HDLS ϭ hereditary diffuse leukoencephalopathy with spheroids; MLD ϭ metachromatic leukodystrophy; MS ϭ multiple sclerosis; SI ϭ signal intensity; WM ϭ white matter; WNL ϭ white matter lesion; X-ALD ϭ X-linked adrenoleukodystrophy.

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Section: Resultsmentioning

confidence: 81%

MRI characteristics and scoring in HDLS due to CSF1R gene mutations

Sundal¹,

Gerpen²,

Nicholson³

et al. 2012

Neurology

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“…The lack of a family history does not preclude the possibility of HDLS, as several sporadic patients who fulfill the clinical and neuropathological criteria for HDLS have been reported (4,5,8,21). Furthermore, the occurrence of HDLS due to a de novo CSF1R mutation has hitherto been confirmed in two families in which the parents of the patient had no mutations of interest (1,8), and one such family was newly added in this study (patient 6).…”

Section: Discussionmentioning

confidence: 84%

Corpus Callosum Atrophy in Patients with Hereditary Diffuse Leukoencephalopathy with Neuroaxonal Spheroids: An MRI-based Study

et al. 2014

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Objective Hereditary diffuse leukoencephalopathy with neuroaxonal spheroids (HDLS) is an adult-onset white matter disease that presents clinically with cognitive, mental and motor dysfunction. Several autopsy reports have indicated that the corpus callosum (CC), the largest bundle of white matter, is severely affected in patients with HDLS. The aim of this study was to evaluate corpus callosum atrophy (CCA) quantitatively in HDLS patients. Methods We assessed CCA in six genetically-proven HDLS patients (HDLS group), in comparison with that observed in 20 patients with vascular dementia (VaD group) and 24 age-matched patients without organic central nervous system (CNS) disease (non-CNS group). Using midsagittal MR images, five measurements of the CC were obtained: the width of the rostrum (aa'), body (bb') and splenium (cc'), the anterior to posterior length (ab) and the maximum height (cd). Next, the corpus callosum index (CCI) was calculated as (aa' + bb' + cc')/ab. Results All HDLS patients had white matter lesions in the CC and frontoparietal lobes on the initial MRI scans. Compared with that observed in the VaD and age-matched non-CNS groups, the CCI was significantly decreased in the HDLS group (with VaD group, p<0.01; with non-CNS group, p<0.01). Conclusion This study showed significant atrophy of the CC in all HDLS patients on the initial MRI scans obtained 6-36 months after onset. We propose that the early appearance of CCA, frequently accompanied by high-intensity in the genu and/or splenium, on T2 images is an important diagnostic clue to HDLS.Key words: hereditary diffuse leukoencephalopathy with neuroaxonal spheroids (HDLS), colony stimulating factor 1 receptor (CSF1R), white matter lesions (WMLs), corpus callosum atrophy (CCA), corpus callosum index (CCI)

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“…2 Currently, eight HDLS families worldwide have been identified in Sweden, Japan, the Netherlands, Australia, and the United States. [1][2][3][4][5][6][7][8] Occasionally, sporadic patients have been reported with a similar disease, [9][10][11][12][13][14] and some have found that the pathology of HDLS is indistinguishable from that of the pigmentary type of orthochromatic leukodystrophy (POLD). 4,15 The non-hereditary cases have been labeled variably, including as leukoencephalopathy with neuroaxonal spheroids (LENAS) 11 and neuroaxonal leukodystrophy (NAL).…”

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confidence: 99%

Insights into the dynamics of hereditary diffuse leukoencephalopathy with axonal spheroids

et al. 2008

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Objective: To report a new American family with hereditary diffuse leukoencephalopathy with spheroids (HDLS), including serial, presymptomatic and symptomatic, cranial MRIs from the proband. Methods:We report clinical and genealogic investigations of an HDLS family, sequential brain MRIs of the proband, and autopsy slides of brain tissue from the proband's father. Results:We identified seven affected family members (five deceased). The mean age at symptomatic disease onset was 35 years (range: 20 -57), and the mean disease duration was 16 years (range: 3-46). Five affected individuals initially manifested memory disturbance and behavioral changes, whereas two experienced a mood disorder as their presenting symptom. Our proband's father had been diagnosed clinically with vascular dementia, but his brain autopsy was consistent with HDLS. The proband had a cranial MRI prior to symptom onset, with two subsequent MRIs performed during follow-up. These serial images reveal a progressive, confluent, frontalpredominant leukoencephalopathy with symmetric cortical atrophy. Conclusions:The proband of our newly identified hereditary diffuse leukoencephalopathy with spheroids (HDLS) kindred had subtle evidence of an incipient leukoencephalopathy on a presymptomatic cranial MRI. Conceivably, MRI may facilitate identifying affected presymptomatic individuals within known HDLS kindreds, increasing the likelihood of isolating the causative genes.

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Sporadic adult-onset leukoencephalopathy with neuroaxonal spheroids mimicking cerebral MS

Cited by 52 publications

References 22 publications

MRI characteristics and scoring in HDLS due to CSF1R gene mutations

MRI characteristics and scoring in HDLS due to CSF1R gene mutations

Corpus Callosum Atrophy in Patients with Hereditary Diffuse Leukoencephalopathy with Neuroaxonal Spheroids: An MRI-based Study

Insights into the dynamics of hereditary diffuse leukoencephalopathy with axonal spheroids

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