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Axonal spheroids

MedGen UID:
479704
•Concept ID:
C3278074
•
Finding
HPO: HP:6000717

Definition

During neurodegeneration, bubble-like swellings form along the length of the axon, a primary and early effect of dynamic axonal deformation. These varicosities, spheroids, or swellings have been described as beads on a string and branches bearing fruit, and they frequently appear on degenerating axons. [from HPO]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVAxonal spheroids

Professional guidelines

PubMed

Evaluation of CSF1R-related adult onset leukoencephalopathy with axonal spheroids and pigmented glia diagnostic criteria.
Ayrignac X, Carra-Dallière C, Codjia P, Mouzat K, Castelnovo G, Ellie E, Etcharry-Bouyx F, Belliard S, Marelli C, Portet F, Le Ber I, Durand-Dubief F, Mathey G, Stankoff B, Dorboz I, Drunat S, Boespflug-Tanguy O, Menjot de Champfleur N, Lumbroso S, Mochel F, Labauge P
Eur J Neurol 2022 Jan;29(1):329-334. Epub 2021 Sep 28 doi: 10.1111/ene.15115. PMID: 34541732
Diagnostic criteria for adult-onset leukoencephalopathy with axonal spheroids and pigmented glia due to CSF1R mutation.
Konno T, Yoshida K, Mizuta I, Mizuno T, Kawarai T, Tada M, Nozaki H, Ikeda SI, Onodera O, Wszolek ZK, Ikeuchi T
Eur J Neurol 2018 Jan;25(1):142-147. Epub 2017 Oct 19 doi: 10.1111/ene.13464. PMID: 28921817Free PMC Article
Amyotrophic lateral sclerosis brain banking: a proposal to standardize protocols and neuropathological diagnostic criteria.
Cruz-Sánchez FF, Moral A, de Belleroche J, Rossi ML
J Neural Transm Suppl 1993;39:215-22. PMID: 8360661

Recent clinical studies

Etiology

Hematopoietic stem cell transplantation in leukodystrophies.
Sevin C, Mochel F
Handb Clin Neurol 2024;204:355-366. doi: 10.1016/B978-0-323-99209-1.00017-X. PMID: 39322389
Validation Study of the MDS Criteria for the Diagnosis of Multiple System Atrophy in the Mayo Clinic Brain Bank.
Sekiya H, Koga S, Murakami A, Kawazoe M, Kim M, Martin NB, Uitti RJ, Cheshire WP, Wszolek ZK, Dickson DW
Neurology 2023 Dec 12;101(24):e2460-e2471. Epub 2023 Oct 10 doi: 10.1212/WNL.0000000000207905. PMID: 37816641Free PMC Article
An update on clinical, pathological, diagnostic, and therapeutic perspectives of childhood leukodystrophies.
Ashrafi MR, Amanat M, Garshasbi M, Kameli R, Nilipour Y, Heidari M, Rezaei Z, Tavasoli AR
Expert Rev Neurother 2020 Jan;20(1):65-84. Epub 2019 Dec 12 doi: 10.1080/14737175.2020.1699060. PMID: 31829048
Adulthood leukodystrophies.
Köhler W, Curiel J, Vanderver A
Nat Rev Neurol 2018 Feb;14(2):94-105. Epub 2018 Jan 5 doi: 10.1038/nrneurol.2017.175. PMID: 29302065Free PMC Article
Neurodegeneration with brain iron accumulation.
Wiethoff S, Houlden H
Handb Clin Neurol 2017;145:157-166. doi: 10.1016/B978-0-12-802395-2.00011-0. PMID: 28987166

Diagnosis

Validation Study of the MDS Criteria for the Diagnosis of Multiple System Atrophy in the Mayo Clinic Brain Bank.
Sekiya H, Koga S, Murakami A, Kawazoe M, Kim M, Martin NB, Uitti RJ, Cheshire WP, Wszolek ZK, Dickson DW
Neurology 2023 Dec 12;101(24):e2460-e2471. Epub 2023 Oct 10 doi: 10.1212/WNL.0000000000207905. PMID: 37816641Free PMC Article
Diffusion-Weighted Imaging is Key to Diagnosing Specific Diseases.
Tokumaru AM, Saito Y, Murayma S
Magn Reson Imaging Clin N Am 2021 May;29(2):163-183. doi: 10.1016/j.mric.2021.02.001. PMID: 33902901
Distinctive diffusion-weighted imaging features in late-onset genetic leukoencephalopathies.
De Cocker LJL, Castillo M
Neuroradiology 2021 Jan;63(1):153-156. Epub 2020 Sep 3 doi: 10.1007/s00234-020-02543-4. PMID: 32879996
An update on clinical, pathological, diagnostic, and therapeutic perspectives of childhood leukodystrophies.
Ashrafi MR, Amanat M, Garshasbi M, Kameli R, Nilipour Y, Heidari M, Rezaei Z, Tavasoli AR
Expert Rev Neurother 2020 Jan;20(1):65-84. Epub 2019 Dec 12 doi: 10.1080/14737175.2020.1699060. PMID: 31829048
Adulthood leukodystrophies.
Köhler W, Curiel J, Vanderver A
Nat Rev Neurol 2018 Feb;14(2):94-105. Epub 2018 Jan 5 doi: 10.1038/nrneurol.2017.175. PMID: 29302065Free PMC Article

Therapy

Dopamine Pathway and Parkinson's Risk Variants Are Associated with Levodopa-Induced Dyskinesia.
Sosero YL, Bandres-Ciga S, Ferwerda B, Tocino MTP, Belloso DR, Gómez-Garre P, Faouzi J, Taba P, Pavelka L, Marques TM, Gomes CPC, Kolodkin A, May P, Milanowski LM, Wszolek ZK, Uitti RJ, Heutink P, van Hilten JJ, Simon DK, Eberly S, Alvarez I, Krohn L, Yu E, Freeman K, Rudakou U, Ruskey JA, Asayesh F, Menéndez-Gonzàlez M, Pastor P, Ross OA, Krüger R; NCER‐PD Consortium, Corvol JC, Koks S, Mir P, De Bie RMA, Iwaki H, Gan-Or Z; International Parkinson's Disease Genomic Consortium
Mov Disord 2024 Oct;39(10):1773-1783. Epub 2024 Aug 12 doi: 10.1002/mds.29960. PMID: 39132902Free PMC Article
Specific Biomarkers in Spinocerebellar Ataxia Type 3: A Systematic Review of Their Potential Uses in Disease Staging and Treatment Assessment.
Soto-Piña AE, Pulido-Alvarado CC, Dulski J, Wszolek ZK, Magaña JJ
Int J Mol Sci 2024 Jul 24;25(15) doi: 10.3390/ijms25158074. PMID: 39125644Free PMC Article
Toxic leukoencephalopathy with axonal spheroids caused by chemotherapeutic drugs other than methotrexate.
Lim KY, Kim SI, Kim H, Kang J, Park JW, Won JK, Shin DY, Park SH
BMC Neurol 2022 Aug 3;22(1):288. doi: 10.1186/s12883-022-02818-8. PMID: 35922754Free PMC Article
Pathology of toxic leucoencephalopathy in drug abuse supports hypoxic-ischemic pathophysiology/etiology.
Alturkustani M, Ang LC, Ramsay D
Neuropathology 2017 Aug;37(4):321-328. Epub 2017 Mar 9 doi: 10.1111/neup.12377. PMID: 28276094
Parkinsonian features in hereditary diffuse leukoencephalopathy with spheroids (HDLS) and CSF1R mutations.
Sundal C, Fujioka S, Van Gerpen JA, Wider C, Nicholson AM, Baker M, Shuster EA, Aasly J, Spina S, Ghetti B, Roeber S, Garbern J, Tselis A, Swerdlow RH, Miller BB, Borjesson-Hanson A, Uitti RJ, Ross OA, Stoessl AJ, Rademakers R, Josephs KA, Dickson DW, Broderick D, Wszolek ZK
Parkinsonism Relat Disord 2013 Oct;19(10):869-77. Epub 2013 Jun 17 doi: 10.1016/j.parkreldis.2013.05.013. PMID: 23787135Free PMC Article

Prognosis

Hematopoietic stem cell transplantation in leukodystrophies.
Sevin C, Mochel F
Handb Clin Neurol 2024;204:355-366. doi: 10.1016/B978-0-323-99209-1.00017-X. PMID: 39322389
Validation Study of the MDS Criteria for the Diagnosis of Multiple System Atrophy in the Mayo Clinic Brain Bank.
Sekiya H, Koga S, Murakami A, Kawazoe M, Kim M, Martin NB, Uitti RJ, Cheshire WP, Wszolek ZK, Dickson DW
Neurology 2023 Dec 12;101(24):e2460-e2471. Epub 2023 Oct 10 doi: 10.1212/WNL.0000000000207905. PMID: 37816641Free PMC Article
Adulthood leukodystrophies.
Köhler W, Curiel J, Vanderver A
Nat Rev Neurol 2018 Feb;14(2):94-105. Epub 2018 Jan 5 doi: 10.1038/nrneurol.2017.175. PMID: 29302065Free PMC Article
Mitochondrial membrane protein-associated neurodegeneration (MPAN).
Hartig M, Prokisch H, Meitinger T, Klopstock T
Int Rev Neurobiol 2013;110:73-84. doi: 10.1016/B978-0-12-410502-7.00004-1. PMID: 24209434
Pantothenate kinase-associated neurodegeneration (Hallervorden-Spatz syndrome).
Gordon N
Eur J Paediatr Neurol 2002;6(5):243-7. doi: 10.1053/ejpn.2002.0606. PMID: 12374576

Clinical prediction guides

Therapeutic potential of human microglia transplantation in a chimeric model of CSF1R-related leukoencephalopathy.
Chadarevian JP, Hasselmann J, Lahian A, Capocchi JK, Escobar A, Lim TE, Le L, Tu C, Nguyen J, Kiani Shabestari S, Carlen-Jones W, Gandhi S, Bu G, Hume DA, Pridans C, Wszolek ZK, Spitale RC, Davtyan H, Blurton-Jones M
Neuron 2024 Aug 21;112(16):2686-2707.e8. Epub 2024 Jun 18 doi: 10.1016/j.neuron.2024.05.023. PMID: 38897209
Systematic rare variant analyses identify RAB32 as a susceptibility gene for familial Parkinson's disease.
Hop PJ, Lai D, Keagle PJ, Baron DM, Kenna BJ, Kooyman M, Shankaracharya, Halter C, Straniero L, Asselta R, Bonvegna S, Soto-Beasley AI; Project MinE ALS Sequencing Consortium, Wszolek ZK, Uitti RJ, Isaias IU, Pezzoli G, Ticozzi N, Ross OA, Veldink JH, Foroud TM, Kenna KP, Landers JE
Nat Genet 2024 Jul;56(7):1371-1376. Epub 2024 Jun 10 doi: 10.1038/s41588-024-01787-7. PMID: 38858457Free PMC Article
Axonal spheroids in neurodegeneration.
Yong Y, Hunter-Chang S, Stepanova E, Deppmann C
Mol Cell Neurosci 2021 Dec;117:103679. Epub 2021 Oct 19 doi: 10.1016/j.mcn.2021.103679. PMID: 34678457Free PMC Article
Neurodegeneration with brain iron accumulation.
Wiethoff S, Houlden H
Handb Clin Neurol 2017;145:157-166. doi: 10.1016/B978-0-12-802395-2.00011-0. PMID: 28987166
Mitochondrial membrane protein-associated neurodegeneration (MPAN).
Hartig M, Prokisch H, Meitinger T, Klopstock T
Int Rev Neurobiol 2013;110:73-84. doi: 10.1016/B978-0-12-410502-7.00004-1. PMID: 24209434

Recent systematic reviews

Specific Biomarkers in Spinocerebellar Ataxia Type 3: A Systematic Review of Their Potential Uses in Disease Staging and Treatment Assessment.
Soto-Piña AE, Pulido-Alvarado CC, Dulski J, Wszolek ZK, Magaña JJ
Int J Mol Sci 2024 Jul 24;25(15) doi: 10.3390/ijms25158074. PMID: 39125644Free PMC Article
Brain abnormalities, neurodegeneration, and dysosteosclerosis (BANDDOS): new cases, systematic literature review, and associations with CSF1R-ALSP.
Dulski J, Souza J, Santos ML, Wszolek ZK
Orphanet J Rare Dis 2023 Jun 22;18(1):160. doi: 10.1186/s13023-023-02772-9. PMID: 37349768Free PMC Article
Neuroimaging phenotypes of CSF1R-related leukoencephalopathy: Systematic review, meta-analysis, and imaging recommendations.
Mickeviciute GC, Valiuskyte M, Plattén M, Wszolek ZK, Andersen O, Danylaité Karrenbauer V, Ineichen BV, Granberg T
J Intern Med 2022 Mar;291(3):269-282. Epub 2021 Dec 22 doi: 10.1111/joim.13420. PMID: 34875121
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
J Clin Neurosci 2018 Feb;48:42-49. Epub 2017 Nov 6 doi: 10.1016/j.jocn.2017.10.060. PMID: 29122458
Neurohistopathological findings at the electrode-tissue interface in long-term deep brain stimulation: systematic literature review, case report, and assessment of stimulation threshold safety.
DiLorenzo DJ, Jankovic J, Simpson RK, Takei H, Powell SZ
Neuromodulation 2014 Jul;17(5):405-18; discussion 418. Epub 2014 Jun 20 doi: 10.1111/ner.12192. PMID: 24947418

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