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PubMed This is a summary of 50 peer-reviewed journal articles Updated
Neurology

Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP): A Patient Guide

At a Glance

ALSP is a rare inherited brain disorder usually caused by a CSF1R gene variant. It progressively damages brain white matter, causing cognitive, behavioral, movement, and communication changes; diagnosis combines brain imaging with genetic testing, while care focuses on personalized symptom support.

Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is an ultra-rare, progressive genetic condition that fundamentally changes how the brain maintains its internal wiring. At the heart of the disease is a pathogenic variant (often called a mutation) in the CSF1R gene, which provides instructions for the brain’s primary immune cells, known as microglia [1]. When these cells fail to function correctly, the brain’s “white matter”—the protective insulation that allows nerve signals to travel—begins to break down, leading to a complex array of cognitive, behavioral, and physical symptoms that typically emerge in a person’s 40s [2][3].

For you and your family, the journey often begins with a long period of uncertainty. Most cases of ALSP are inherited in an autosomal dominant pattern. This means if you carry a pathogenic variant, each of your children has a 50% chance of inheriting it. However, because of age-dependent penetrance and variable expressivity, the exact onset and severity are unpredictable. Because the early signs of ALSP—such as subtle personality changes, memory lapses, or a slightly unsteady gait—closely mimic more common conditions, families frequently navigate years of misdiagnoses, frequently being told they have Multiple Sclerosis (MS), Frontotemporal Dementia (FTD), or early-onset Alzheimer’s disease [3][4]. Reaching a definitive diagnosis requires specialized expertise, combining characteristic findings on brain imaging with a confirmatory genetic test to identify the CSF1R pathogenic variant [2][5].

Once a diagnosis is confirmed, the focus shifts to managing a disease that is both progressive and highly variable. No two people experience ALSP in exactly the same way, even within the same family, which means that care must be deeply individualized to your specific needs [6]. While there is currently no universal cure that can reverse the underlying damage, the path forward is built on proactive, multidisciplinary support. A team of specialists—including neurologists, psychiatrists, and therapists—can work together to manage symptoms like movement stiffness, mood changes, and communication difficulties, helping to maintain quality of life for as long as possible [7][8].

In some carefully selected cases, experimental and highly investigational interventions like Hematopoietic Stem Cell Transplant (HSCT) or participation in clinical trials for emerging therapies may be options to discuss [9][10]. Navigating these choices requires a partnership with a medical team that understands the unique challenges of leukodystrophies. While the diagnosis is life-changing, the growing recognition of ALSP in the medical community is leading to better resources, more accurate testing, and a dedicated network of specialists committed to supporting you and your family through every stage of the condition [11][7].

In this guide

6 chapters

01

Understanding Your ALSP Diagnosis

Learn what an ALSP diagnosis means, including CSF1R genetics, MRI and CT clues, inheritance, misdiagnosis, and questions to ask your care team about next steps.

02

Symptoms and Common Misdiagnoses

Learn how ALSP symptoms mimic MS, FTD, early-onset Alzheimer’s, Parkinsonism, and CADASIL, and what disease progression may look like for you and your family.

03

MRI Scans and Genetic Testing

Learn how adult-onset leukoencephalopathy (ALSP) is diagnosed with MRI patterns, CT calcifications, and comprehensive CSF1R testing, including next steps.

04

Symptom Management and Team Care

Learn how ALSP symptoms are managed with a multidisciplinary care team, therapy for movement and swallowing, and guidance on investigational treatment options.

05

The Investigational Role of Stem Cell Transplantation (HSCT)

Learn about investigational HSCT for adult-onset leukoencephalopathy with axonal spheroids and pigmented glia, including eligibility, outcomes, and risks.

06

Daily Life, Monitoring, and Emergencies

Learn how adult-onset leukoencephalopathy (ALSP) affects daily life, with monitoring tips, emergency warning signs, seizure safety, and future care planning.

Common questions in this guide

What causes adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP)?
ALSP is usually caused by a disease-causing change in the CSF1R gene, which affects microglia, the brain’s immune-support cells. Most cases follow a dominant inheritance pattern, meaning a person who carries the gene change can pass it to each child.
What symptoms can ALSP cause?
Symptoms often begin in adulthood and may include personality or mood changes, memory and thinking problems, an unsteady gait, stiffness, and communication difficulties. Early symptoms can resemble multiple sclerosis, frontotemporal dementia, or early-onset Alzheimer disease, so diagnosis may take time.
How is ALSP diagnosed?
Doctors combine characteristic brain-imaging findings with genetic testing for a disease-causing CSF1R variant. Because ALSP can resemble more common conditions, evaluation by a neurologist or a center experienced with leukodystrophies may help confirm the diagnosis.
If I have ALSP, what is the chance my child will inherit it?
When a parent carries the ALSP-related CSF1R variant, each child has a 50% chance of inheriting it. The age when symptoms begin and how severe they become can vary, so genetic counseling is recommended before testing family members.
Is there a cure or treatment for ALSP?
There is currently no universal cure that reverses the underlying brain damage. Individualized care may include medicines, physical or speech therapy, and support from neurology, psychiatry, and other specialists; hematopoietic stem cell transplant and clinical trials remain investigational options for selected patients.
What kind of care team is helpful for someone with ALSP?
Care is usually coordinated by a multidisciplinary team that may include a neurologist, psychiatrist, genetic counselor, and physical or speech therapist. The team can tailor symptom management, monitor changes, and help the patient and family plan daily support and future care.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.What specific medical specialty will lead our multidisciplinary care team?
  2. 2.Is there a nearby center of excellence with experience in managing CSF1R-related leukodystrophies?
  3. 3.Can you help us coordinate genetic counseling and testing for other adult family members who may be at risk?
  4. 4.How do we distinguish between symptoms that can be managed with medication and those that require physical or speech therapy?
  5. 5.Are there any current clinical trials or research registries our family should consider joining?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

References

References (11)
  1. 1

    Insights Into the Role of CSF1R in the Central Nervous System and Neurological Disorders.

    Hu B, Duan S, Wang Z, et al.

    Frontiers in aging neuroscience 2021; (13()):789834 doi:10.3389/fnagi.2021.789834.

    PMID: 34867307
  2. 2

    Identification and functional characterization of novel mutations including frameshift mutation in exon 4 of CSF1R in patients with adult-onset leukoencephalopathy with axonal spheroids and pigmented glia.

    Miura T, Mezaki N, Konno T, et al.

    Journal of neurology 2018; (265(10)):2415-2424 doi:10.1007/s00415-018-9017-2.

    PMID: 30136118
  3. 3

    Clinical presentation and diagnosis of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia: a literature analysis of case studies.

    Papapetropoulos S, Gelfand JM, Konno T, et al.

    Frontiers in neurology 2024; (15()):1320663 doi:10.3389/fneur.2024.1320663.

    PMID: 38529036
  4. 4

    Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP): Integrating the literature on hereditary diffuse leukoencephalopathy with spheroids (HDLS) and pigmentary orthochromatic leukodystrophy (POLD).

    Adams SJ, Kirk A, Auer RN

    Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia 2018; (48()):42-49 doi:10.1016/j.jocn.2017.10.060.

    PMID: 29122458
  5. 5

    Evaluation of CSF1R-related adult onset leukoencephalopathy with axonal spheroids and pigmented glia diagnostic criteria.

    Ayrignac X, Carra-Dallière C, Codjia P, et al.

    European journal of neurology 2022; (29(1)):329-334 doi:10.1111/ene.15115.

    PMID: 34541732
  6. 6

    Clinical and genetic characterization of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia associated with CSF1R mutation.

    Konno T, Yoshida K, Mizuno T, et al.

    European journal of neurology 2017; (24(1)):37-45 doi:10.1111/ene.13125.

    PMID: 27680516
  7. 7

    Adult-Onset Leukoencephalopathy With Axonal Spheroids and Pigmented Glia: Review of Clinical Manifestations as Foundations for Therapeutic Development.

    Papapetropoulos S, Pontius A, Finger E, et al.

    Frontiers in neurology 2021; (12()):788168 doi:10.3389/fneur.2021.788168.

    PMID: 35185751
  8. 8

    Movement Disorders in CSF1R -Related Leukoencephalopathy: A Case Series.

    Kamble N, Harishma RS, Holla VV, et al.

    Annals of Indian Academy of Neurology 2025; (28(4)):596-598 doi:10.4103/aian.aian_51_25.

    PMID: 40503581
  9. 9

    Hematopoietic Stem Cell Transplantation in CSF1R-Related Leukoencephalopathy: Retrospective Study on Predictors of Outcomes.

    Dulski J, Heckman MG, White LJ, et al.

    Pharmaceutics 2022; (14(12)) doi:10.3390/pharmaceutics14122778.

    PMID: 36559271
  10. 10

    Rescue of in vitro models of CSF1R-related adult-onset leukodystrophy by iluzanebart: mechanisms and therapeutic implications of TREM2 agonism.

    Larson KC, Gergits FW, Renoux AJ, et al.

    Journal of neuroinflammation 2025; (22(1)):26 doi:10.1186/s12974-025-03346-1.

    PMID: 39891235
  11. 11

    Mapping the journey of patients and care partners living with adult-onset leukoencephalopathy with axonal spheroids and pigmented glia: developing a framework for improvements in care.

    Rutherford HA, Rush BK, Smith A, et al.

    Neurodegenerative disease management 2024; (14(5)):161-172 doi:10.1080/17582024.2024.2404378.

    PMID: 39363647

This ALSP page is for informational purposes only and does not constitute medical advice. Your neurologist, genetic counselor, and multidisciplinary team can interpret CSF1R results and discuss care options for your situation.

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