Journal of Movement Disorders

Brief communication

Hematopoietic Stem Cell Transplantation for CSF1R-Related Disorder: A Longitudinal Study of Efficacy and Safety: Tomasz Chmiela, Kamila Żur-Wyrozumska, Patrycja Mensah-Glanowska, Audrey J. Strongosky, Erik H. Middlebrooks, Ernesto Ayala, Zbigniew K. Wszolek; J Mov Disord. 2026;19(3):322-326. Published online February 27, 2026; DOI: https://doi.org/10.14802/jmd.26005

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Objective
This longitudinal study evaluated the long-term efficacy and safety of hematopoietic stem cell transplantation (HSCT) in slowing the progression of CSF1R-related disorder (CSF1R-RD).
Methods
Six symptomatic patients (mean follow-up, 6.6 years) were compared with six matched, untreated controls. The CSF1R Clinical Severity Score (CCSS), Montreal Cognitive Assessment, and Sundal radiological score were used for evaluation.
Results
Post-HSCT clinical progression slowed significantly from 14.1 to 3.7 CCSS/year, compared with 15.2 CCSS/year in the control group (p<0.01). Cognitive decline was substantially reduced (-1.5 points/year vs. -7.6 points/year), and radiological deterioration slowed (0.4 per year vs. 3.9 per year). Notably, during the observation period, all HSCT patients survived, whereas 50% of the patients in the control group died. No serious transplant-related complications were observed.
Conclusion
HSCT is a potent disease-modifying therapy for CSF1R-RD that drastically improves survival and slows deterioration. These findings underscore the necessity of early intervention during the symptomatic phase to maximize the preservation of quality of life for affected individuals.

Citations

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The path to clinical application of human microglia transplantation for the treatment of CSF1R-related disorder
Tomasz Chmiela, Robert C. Spitale, Zbigniew K. Wszolek
Expert Review of Neurotherapeutics.2026; 26(7): 653. CrossRef
CSF1R-related leukoencephalopathy: experimental models and potential for treatment
David A. Hume, Katharine M. Irvine
Disease Models & Mechanisms.2026;[Epub] CrossRef

Original Article

Clinical and Pathological Features of CSF1R-Related Disorder Associated With the p.R777Q Pathogenic Variant: Tomasz Chmiela, Delaney Liskey, Audrey J. Strongosky, Stuart J. McCarter, Paula Sandroni, Dennis W. Dickson, Zbigniew K. Wszolek; J Mov Disord. 2026;19(2):135-144. Published online November 14, 2025; DOI: https://doi.org/10.14802/jmd.25247

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Abstract PDF

Objective
Colony-stimulating factor-1 receptor (CSF1R)-related disorder (CSF1R-RD) is a rapidly progressive neurodegenerative disease with a median onset of 43 years. More than 200 CSF1R pathogenic variants have been identified. Patients develop rapidly progressive dementia and motor symptoms, with a median disease duration of 6.8 years. The p.R777Q variant causes CSF1R-RD; it is deleterious to protein function. We describe the clinical and pathological features of CSF1R-RD associated with p.R777Q and report a new family carrying this variant. We compare the neuropathological findings of an index patient (with short-duration disease) with those of a patient with long-duration CSF1R-RD.
Methods
We present clinical and imaging data from a new family with p.R777Q. We also describe the neuropathology of an index patient and contrast these findings with features of a patient with CSF1R-RD with an 11-year disease course caused by the c.2656_2657insC variant.
Results
We reviewed the literature on 13 individuals from 8 families with the p.R777Q variant from Asia, Europe, and North America. The mean age at onset was 41±14 years, ranging from 22 to 63 years, and the mean survival was 3.3±2.5 years. Neuropathologic studies of our index patient (10-month disease duration) revealed features consistent with CSF1R-RD. Axonal and myelin pathology was severe in the periventricular white matter. Compared with the patient with an 11-year disease duration, the index patient had less severe white matter lesions.
Conclusion
Compared with CSF1R-RD associated with other variants, the p.R777Q variant has an aggressive course. Compared with the patient with a long disease duration, the index patient had milder neuropathological findings. These differences may be specific to p.R777Q or associated with rapid clinical progression.

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The path to clinical application of human microglia transplantation for the treatment of CSF1R-related disorder
Tomasz Chmiela, Robert C. Spitale, Zbigniew K. Wszolek
Expert Review of Neurotherapeutics.2026; 26(7): 653. CrossRef

Brief communication

CSF1R-Related Adult-Onset Leukoencephalopathy With Axonal Spheroids: A Case Series of Four Asian Indian Patients: Divyani Garg, Abhishek Vaingankar, Anu Gupta, Roopa Rajan, Ajay Garg, Ayush Agarwal, Farsana Mustafa, Divya M Radhakrishnan, Awadh Kishor Pandit, Venugopalan Y Vishnu, Mamta Bhushan Singh, Rohit Bhatia, Achal Kumar Srivastava; J Mov Disord. 2025;18(2):170-174. Published online February 17, 2025; DOI: https://doi.org/10.14802/jmd.25004

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Abstract PDF Supplementary Material

Objective
Colony-stimulating factor 1 receptor-related leukoencephalopathy (CSF1R-L) is a rare adult-onset leukoencephalopathy. Reports of CSF1R-L patients from the Indian subcontinent remain limited. We aimed to report four patients with genetically confirmed CSF1R-L from four Asian Indian families and described their clinical, molecular, and radiological features.
Methods
All patients underwent clinical examination, brain magnetic resonance imaging, and whole-exome sequencing to identify causative variants in the CSF1R gene. We also reviewed published reports of Indian patients with CSF1R-L.
Results
The age at enrollment ranged from 34 to 40 years. The duration of symptoms ranged from 11 months to 2 years. The chief clinical phenotype in three patients was a rapidly evolving cognitive-behavioral syndrome combined with atypical parkinsonism, and asymmetrical spastic tetraparesis was observed in one patient. We identified four different variants (three missense variants and one in-frame deletion). Radiological findings revealed white matter involvement and diffusion restriction involving the subcortical white matter and pyramidal tracts.
Conclusion
We expand the literature on CSF1R-L patients from India by reporting four new cases.

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A novel mutation in colony-stimulating factor 1 receptor (CSF1R) causing CSF1R-related disorder (CSF1R-RD)
Anup N. Sonti, Elizabeth Joe, Jillian V. Berry, Michelle McDonnell, Seyed Ahmad Sajjadi, Nasim Sheik-Bahaei, Lilyana Amezcua, Danielle Feigenbaum, Mark F. Lew, Matthew Blurton-Jones, Elizabeth Head, John M. Ringman
Neurocase.2026; 32(1): 13. CrossRef
Movement Disorders in CSF1R-Related Leukoencephalopathy: A Case Series
Nitish Kamble, RS Harishma, Vikram V Holla, Shweta Prasad, Jitender Saini, Pramod K Pal
Annals of Indian Academy of Neurology.2025; 28(4): 596. CrossRef

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.

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A rare case of adult-onset vanishing white matter leukoencephalopathy with movement disorder, expressing homozygous EIF2B3 and PRKN pathogenic variants
Bashar Kamal Ali Douden, Yazan Mohammad Abdullah Abufara, Mahmood Fayez Ali Aldrabeeh, Naela Ramadan Mohammad Tell, Ismail Abudaya
BMC Neurology.2025;[Epub] CrossRef

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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Abstract PDF Supplementary Material

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; 106(1): 56. CrossRef
Most common NOTCH3 mutations causing CADASIL or CADASIL-like cerebral small vessel disease: A systematic review
Georgina Boston, Dan Jobson, Toshiki Mizuno, Masafumi Ihara, Raj N Kalaria
Cerebral Circulation - Cognition and Behavior.2024; 6: 100227. CrossRef
Investigating the genetic basis of hereditary spastic paraplegia and cerebellar Ataxia in Pakistani families
Arfa Azeem, Asif Naveed Ahmed, Niamat Khan, Nikol Voutsina, Irfan Ullah, Nishanka Ubeyratna, Muhammad Yasin, Emma L. Baple, Andrew H. Crosby, Lettie E. Rawlins, Shamim Saleha
BMC Neurology.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

Late-onset CSF1R-related Disorder: A Case Report
Lixue Chen, Haoyou Xu, Zhifu Lu
Cognitive and Behavioral Neurology.2025; 38(1): 16. CrossRef
Suspected Postpartum Depression Revealed to be CSF1R-Related Leukoencephalopathy: A Case Report
Masahiko Mikuni, Kazuhiro Horiuchi, Ayako Ishikura, Soichiro Kimura, Sho Masutani, Shinya Watanabe, Akihiro Mikami, Shuhei Ishikawa, Hisashi Narita, Ichiro Kusumi, Hidenao Sasaki
Case Reports in Neurology.2024; 16(1): 281. CrossRef
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.2024; 15(2): 101. 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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