Journal of Movement Disorders

Review Article

Adult-Onset Genetic Leukoencephalopathies With Movement Disorders: Mu-Hui Fu, Yung-Yee Chang; J Mov Disord. 2023;16(2):115-132. Published online March 7, 2023; DOI: https://doi.org/10.14802/jmd.22127

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Abstract PDF: Genetic leukoencephalopathies (GLEs) are a group of white matter abnormalities with heterogeneous radiological and phenotypic features. Although these conditions have mostly been described in children, adult-onset cases are increasingly recognized owing to the widespread use of neuroimaging and advances in molecular genetic testing. The disease course is often progressive with a varied spectrum of presentations, trapping neurologists in the dilemma of differential diagnosis. Movement disorders are among the most common symptoms, and their diversity makes diagnosis challenging. In this review, we focus on adult-onset GLEs with movement disorders and offer a step-by-step diagnostic approach by clarifying the phenomenology of movement, advising investigations for acquired causes, describing the clinical and radiological clues to each disease, emphasizing the limitations of advanced molecular testing, and discussing the future application of artificial intelligence. We provide a list summarizing the leukoencephalopathies associated with different categories of movement disorders. In addition to guiding clinicians on how to narrow the list of differential diagnoses with the tools currently available, another aim of this review is to emphasize the inevitable trend toward applying advanced technology in diagnosing these difficult diseases.

Case Reports

Extensive Leukoencephalopathy in Spastic Paraplegia Type 4: Possible Role of Cerebral Autosomal Arteriopathy With Subcortical Infarcts and Leukoencephelopathy: Jin Ho Jung, Jung Hwa Seo, Sukyoon Lee, Young Jin Heo, Donghyun Kim, Eun Joo Chung, Seong-il Oh; J Mov Disord. 2022;15(1):71-74. Published online December 24, 2021; DOI: https://doi.org/10.14802/jmd.21091

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Despite recent advances in next-generation sequencing, the underlying etiology of adult-onset leukoencephalopathy has been difficult to elucidate. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a representative hereditary adult-onset leukoencephalopathy associated with vasculopathy. Leukoencephalopathy in spastic paraplegia type 4 (SPG4) is known to be rare, but it might be underestimated because most spastic paraplegia with leukoencephalopathy is rarely considered. We report a case of co-occurring SPG4 and CADASIL. A 61-year-old male presented with sudden visual impairment after a headache. He showed a spastic gait and had a family history with similar symptoms. An SPG4 gene mutation and a pathogenic variant in the NOTCH3 gene were found. This case shows that the diverse and complex clinical manifestations of patients with extensive leukoencephalopathy are related to more than one gene mutation. We also suggest the necessity for relevant genetic tests in the diagnosis of adult-onset leukoencephalopathy.

Citations

Citations to this article as recorded by

Clinical and genetic characteristics in a Chinese cohort of complex spastic paraplegia type 4
Li Yao, Yuwen Cao, Chao Zhang, Xiaojun Huang, Wotu Tian, Li Cao
Clinical Genetics.2024;[Epub] CrossRef

Suspected Perinatal Depression Revealed to be Hereditary Diffuse Leukoencephalopathy with Spheroids: Josefine Blume, Robert Weissert; J Mov Disord. 2017;10(1):59-61. Published online December 27, 2016; DOI: https://doi.org/10.14802/jmd.16050

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Abstract PDF Supplementary Material

Early motor symptoms of neurodegenerative diseases often appear in combination with psychiatric symptoms, such as depression or personality changes, and are in danger of being misdiagnosed as psychogenic in young patients. We present the case of a 32-year-old woman who presented with rapid-onset depression, followed by a hypokinetic movement disorder and cognitive decline during pregnancy. Genetic testing revealed a mutation in the colony-stimulating factor 1 receptor gene, which led to the diagnosis of hereditary diffuse leukoencephalopathy with spheroids. Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is probably an under-recognized disease. HDLS should be considered in patients with rapidly progressing parkinsonian symptoms and dementia accompanied by white matter lesions.

Citations

Citations to this article as recorded by

Modeling CSF‐1 receptor deficiency diseases – how close are we?
Violeta Chitu, Şölen Gökhan, E. Richard Stanley
The FEBS Journal.2022; 289(17): 5049. CrossRef
Neuroimaging phenotypes of CSF1R‐related leukoencephalopathy: Systematic review, meta‐analysis, and imaging recommendations
Goda‐Camille Mickeviciute, Monika Valiuskyte, Michael Plattén, Zbigniew K. Wszolek, Oluf Andersen, Virginija Danylaité Karrenbauer, Benjamin V. Ineichen, Tobias Granberg
Journal of Internal Medicine.2022; 291(3): 269. CrossRef
A Novel Missense Mutation of the CSF1R Gene Causes Incurable CSF1R-Related Leukoencephalopathy: Case Report and Review of Literature
Jie Chen, Shiying Luo, Ning Li, Huimin Li, Jinming Han, Li Ling
International Journal of General Medicine.2020; Volume 13: 1613. CrossRef
CSF1R -related leukoencephalopathy
Takuya Konno, Koji Kasanuki, Takeshi Ikeuchi, Dennis W. Dickson, Zbigniew K. Wszolek
Neurology.2018; 91(24): 1092. CrossRef

A Cerebellar Tremor in a Patient with Human Immunodeficiency Virus-1 Associated with Progressive Multifocal Leukoencephalopathy: Hee-Jin Kim, Jae-Jung Lee, Phil Hyu Lee; J Mov Disord. 2009;2(2):88-90.; DOI: https://doi.org/10.14802/jmd.09024

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Abstract PDF

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system (CNS) caused by JC virus infection in oligodendrocytes, especially in patients with acquired immunodeficiency syndrome (AIDS). Movement disorders associated with PML are very rare. Here, we report a case of PML in an AIDS patient who presented with a cerebellar tremor, caused by lesions in the cerebellar outflow tract. A cerebellar tremor can be a rare clinical manifestation in patients with PML.

Citations

Citations to this article as recorded by

Holmes tremor in progressive multifocal leukoencephalopathy: A video case report
Takako Matsushima, Ryotaro Ikeguchi, Mutsumi Iijima, Ayato Shimomura, Shuntaro Takahashi, Kazuo Nakamichi, Yuko Shimizu, Kazuo Kitagawa
Clinical and Experimental Neuroimmunology.2023;[Epub] CrossRef
Holmes tremor caused by a natalizumab-related progressive multifocal leukoencephalopathy: a case report and brief review of the literature
Luca Magistrelli, Domizia Vecchio, Paola Naldi, Cristoforo Comi, Roberto Cantello
Neurological Sciences.2019; 40(9): 1943. CrossRef

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