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Comprehensive diagnostics in a case of hereditary diffuse leukodystrophy with spheroids.

Meyer-Ohlendorf M, Braczynski A, Al-Qaisi O, Gessler F, Biskup S, Weise L, Steinbach JP, Wagner M, Mittelbronn M, Bähr O - BMC Neurol (2015)

Bottom Line: After a comprehensive diagnostic workup and exclusion of other leukoencephalopathies, stereotactic biopsy and genetic testing confirmed the diagnosis.This might help to identify more patients with this underdiagnosed disease.Moreover, the rapid clinical course in our patient raises the question whether the relatively pronounced areas of restricted diffusion are indicative of a more acute progression of the disease.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Goethe University Hospital, Frankfurt, Germany. Marie.Meyer-Ohlendorf@kgu.de.

ABSTRACT

Background: Hereditary diffuse leukodystrophy with spheroids is a rare type of leukoencephalopathy. Mutations in the colony stimulating factor 1 receptor have recently been identified to be the cause of this microgliopathy. Clinical and radiological presentation can often misguide physicians during the diagnosis of patients with this underdiagnosed disease.

Case presentation: We present a 29 year-old woman with a rapid course of hereditary diffuse leukodystrophy with spheroids. She mainly showed cognitive impairment and severe motor dysfunctions. Her MRI showed spotted and confluent hyperintensities of the white matter on T2-weighted images involving the corticospinal tract as well as the corpus callosum. Further, those lesions showed striking restricted diffusion. As this restricted diffusion in all areas showing signs of leukoencephalopathy was so impressive we searched Medline for these terms and got hereditary diffuse leukodystrophy with spheroids as one of the first results. After a comprehensive diagnostic workup and exclusion of other leukoencephalopathies, stereotactic biopsy and genetic testing confirmed the diagnosis.

Conclusion: This case points out at two important features of hereditary diffuse leukodystrophy with spheroids being spotted and/or confluent leukoencephalopathy with areas of restricted diffusion. This might help to identify more patients with this underdiagnosed disease. Moreover, the rapid clinical course in our patient raises the question whether the relatively pronounced areas of restricted diffusion are indicative of a more acute progression of the disease.

No MeSH data available.


Related in: MedlinePlus

Electron microscopy. Electron microscopy showing brain tissue with regularly myelinated axons (arrow heads, a + b). Intra-axonal globular inclusions (asterisk, b) were observed reflecting the pathological findings of axon spheroids seen in the light microscopic examination
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Fig5: Electron microscopy. Electron microscopy showing brain tissue with regularly myelinated axons (arrow heads, a + b). Intra-axonal globular inclusions (asterisk, b) were observed reflecting the pathological findings of axon spheroids seen in the light microscopic examination

Mentions: Biopsy specimens from the stereotactic biopsy showed CNS tissue with signs of reactive gliosis and extensive infiltration with CD68-positive macrophages. Furthermore, many axonal spheroids were seen which stained positive for neurofilament (NF) and amyloid precursor protein (APP). The Ki67 proliferation rate was not increased. The myelin was mainly preserved (Fig. 3). In summary, we did not observe hints for an inflammatory or a primary demyelinating disease. JC-virus in situ hybridization to exclude the possibility of a progressive multifocal encephalopathy was negative. The brain biopsy specimens were also negative for CMV, EBV, HSV1/2, as well as VZV. CSF1R immunohistochemistry was negative while control samples revealed positive staining results (Fig. 4). Electron microscopy revealed regularly myelinated axons however several axonal globular inclusions (Fig. 5).Fig. 3


Comprehensive diagnostics in a case of hereditary diffuse leukodystrophy with spheroids.

Meyer-Ohlendorf M, Braczynski A, Al-Qaisi O, Gessler F, Biskup S, Weise L, Steinbach JP, Wagner M, Mittelbronn M, Bähr O - BMC Neurol (2015)

Electron microscopy. Electron microscopy showing brain tissue with regularly myelinated axons (arrow heads, a + b). Intra-axonal globular inclusions (asterisk, b) were observed reflecting the pathological findings of axon spheroids seen in the light microscopic examination
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4491230&req=5

Fig5: Electron microscopy. Electron microscopy showing brain tissue with regularly myelinated axons (arrow heads, a + b). Intra-axonal globular inclusions (asterisk, b) were observed reflecting the pathological findings of axon spheroids seen in the light microscopic examination
Mentions: Biopsy specimens from the stereotactic biopsy showed CNS tissue with signs of reactive gliosis and extensive infiltration with CD68-positive macrophages. Furthermore, many axonal spheroids were seen which stained positive for neurofilament (NF) and amyloid precursor protein (APP). The Ki67 proliferation rate was not increased. The myelin was mainly preserved (Fig. 3). In summary, we did not observe hints for an inflammatory or a primary demyelinating disease. JC-virus in situ hybridization to exclude the possibility of a progressive multifocal encephalopathy was negative. The brain biopsy specimens were also negative for CMV, EBV, HSV1/2, as well as VZV. CSF1R immunohistochemistry was negative while control samples revealed positive staining results (Fig. 4). Electron microscopy revealed regularly myelinated axons however several axonal globular inclusions (Fig. 5).Fig. 3

Bottom Line: After a comprehensive diagnostic workup and exclusion of other leukoencephalopathies, stereotactic biopsy and genetic testing confirmed the diagnosis.This might help to identify more patients with this underdiagnosed disease.Moreover, the rapid clinical course in our patient raises the question whether the relatively pronounced areas of restricted diffusion are indicative of a more acute progression of the disease.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Goethe University Hospital, Frankfurt, Germany. Marie.Meyer-Ohlendorf@kgu.de.

ABSTRACT

Background: Hereditary diffuse leukodystrophy with spheroids is a rare type of leukoencephalopathy. Mutations in the colony stimulating factor 1 receptor have recently been identified to be the cause of this microgliopathy. Clinical and radiological presentation can often misguide physicians during the diagnosis of patients with this underdiagnosed disease.

Case presentation: We present a 29 year-old woman with a rapid course of hereditary diffuse leukodystrophy with spheroids. She mainly showed cognitive impairment and severe motor dysfunctions. Her MRI showed spotted and confluent hyperintensities of the white matter on T2-weighted images involving the corticospinal tract as well as the corpus callosum. Further, those lesions showed striking restricted diffusion. As this restricted diffusion in all areas showing signs of leukoencephalopathy was so impressive we searched Medline for these terms and got hereditary diffuse leukodystrophy with spheroids as one of the first results. After a comprehensive diagnostic workup and exclusion of other leukoencephalopathies, stereotactic biopsy and genetic testing confirmed the diagnosis.

Conclusion: This case points out at two important features of hereditary diffuse leukodystrophy with spheroids being spotted and/or confluent leukoencephalopathy with areas of restricted diffusion. This might help to identify more patients with this underdiagnosed disease. Moreover, the rapid clinical course in our patient raises the question whether the relatively pronounced areas of restricted diffusion are indicative of a more acute progression of the disease.

No MeSH data available.


Related in: MedlinePlus