The field of leukoencephalopathy received a great boost in interest after the role of microglia-related genes became elucidated. Even still being very rare, they are now more commonly detected in countries where genetic testing is available, usually in the Northern Hemisphere. CSF1R-related leukoencephalopathy has been commoner in Japan. It may add up to 10% of all cases of leukoencephalopathies, and may be misdiagnosed as multiple sclerosis.

Takuya Konno and colleagues – Neurology 2018, 91:1092-1104 – reviewed the field. They found that the CSF1R-related leukoencephalopathy starts in the 40s, earlier in women, and lasts 7 years, in average. Neuropsychiatric and motor symptoms are relentless progressive, with apathy, irritability and cognitive decline on one side, parkinsonian, pyramidal, bulbar and cerebelar signs on the other. The clinical picture resembles frontotemporal dementia. MRI shows white matter involvement, and progressive anterior atrophy, with large ventricles. Calcifications are ubiquitous and better demonstrated on CT. Thinning of the corpus callosum accompanies disease progression, and white matter abnormalities become confluent, always more predominant anteriorly.

Axonal spheroids and pigmented macrophages are the pathologic hallmarks of this type of leukoencephalopathy. Because lesions are multifocal, one biopsy specimen may fail to clarify the disease.

Symptomatic therapies are of some help, but only one case treated with hematopoietc stem cell transplantation stopped to progress. That is also the case in metabolic leukoencephalopathy. The disease is autossomic dominant, but sporadic cases have been described, indicating mosaicism and incomplete penetrance.

Dr Paulo Bittencourt

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