Adult-onset leukodystrophies: a practical guide, recent treatment updates, and future directions
Adult-onset leukodystrophies though individually rare are not uncommon. This group includes several disorders with isolated adult presentations, as well as several childhood leukodystrophies with attenuated phenotypes that present at a later age. Misdiagnoses often occur due to the clinical and radi...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-07-01
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| Series: | Frontiers in Neurology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fneur.2023.1219324/full |
| _version_ | 1797772104443101184 |
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| author | Karthik Muthusamy Ajith Sivadasan Luke Dixon Sniya Sudhakar Maya Thomas Sumita Danda Zbigniew K. Wszolek Klaas Wierenga Radhika Dhamija Ralitza Gavrilova |
| author_facet | Karthik Muthusamy Ajith Sivadasan Luke Dixon Sniya Sudhakar Maya Thomas Sumita Danda Zbigniew K. Wszolek Klaas Wierenga Radhika Dhamija Ralitza Gavrilova |
| author_sort | Karthik Muthusamy |
| collection | DOAJ |
| description | Adult-onset leukodystrophies though individually rare are not uncommon. This group includes several disorders with isolated adult presentations, as well as several childhood leukodystrophies with attenuated phenotypes that present at a later age. Misdiagnoses often occur due to the clinical and radiological overlap with common acquired disorders such as infectious, immune, inflammatory, vascular, metabolic, and toxic etiologies. Increased prevalence of non-specific white matter changes in adult population poses challenges during diagnostic considerations. Clinico-radiological spectrum and molecular landscape of adult-onset leukodystrophies have not been completely elucidated at this time. Diagnostic approach is less well-standardized when compared to the childhood counterpart. Absence of family history and reduced penetrance in certain disorders frequently create a dilemma. Comprehensive evaluation and molecular confirmation when available helps in prognostication, early initiation of treatment in certain disorders, enrollment in clinical trials, and provides valuable information for the family for reproductive counseling. In this review article, we aimed to formulate an approach to adult-onset leukodystrophies that will be useful in routine practice, discuss common adult-onset leukodystrophies with usual and unusual presentations, neuroimaging findings, recent advances in treatment, acquired mimics, and provide an algorithm for comprehensive clinical, radiological, and genetic evaluation that will facilitate early diagnosis and consider active treatment options when available. A high index of suspicion, awareness of the clinico-radiological presentations, and comprehensive genetic evaluation are paramount because treatment options are available for several disorders when diagnosed early in the disease course. |
| first_indexed | 2024-03-12T21:46:16Z |
| format | Article |
| id | doaj.art-69fe0cc3850640e493d9a0edebafc3c1 |
| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-03-12T21:46:16Z |
| publishDate | 2023-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neurology |
| spelling | doaj.art-69fe0cc3850640e493d9a0edebafc3c12023-07-26T10:54:04ZengFrontiers Media S.A.Frontiers in Neurology1664-22952023-07-011410.3389/fneur.2023.12193241219324Adult-onset leukodystrophies: a practical guide, recent treatment updates, and future directionsKarthik Muthusamy0Ajith Sivadasan1Luke Dixon2Sniya Sudhakar3Maya Thomas4Sumita Danda5Zbigniew K. Wszolek6Klaas Wierenga7Radhika Dhamija8Ralitza Gavrilova9Department of Clinical Genomics, Mayo Clinic, Jacksonville, FL, United StatesDepartment of Neurological Sciences, Christian Medical College, Tamil Nadu, Vellore, IndiaDepartment of Radiology, Imperial College, NHS Trust, London, United KingdomDepartment of Radiology, Great Ormond Street Hospital, London, United KingdomDepartment of Neurological Sciences, Christian Medical College, Tamil Nadu, Vellore, IndiaDepartment of Medical Genetics, Christian Medical College, Vellore, Tamil Nadu, IndiaDepartment of Neurology, Mayo Clinic, Jacksonville, FL, United StatesDepartment of Clinical Genomics, Mayo Clinic, Jacksonville, FL, United StatesDepartment of Clinical Genomics and Neurology, Mayo Clinic, Phoenix, AZ, United StatesDepartment of Clinical Genomics and Neurology, Mayo Clinic, Rochester, MN, United StatesAdult-onset leukodystrophies though individually rare are not uncommon. This group includes several disorders with isolated adult presentations, as well as several childhood leukodystrophies with attenuated phenotypes that present at a later age. Misdiagnoses often occur due to the clinical and radiological overlap with common acquired disorders such as infectious, immune, inflammatory, vascular, metabolic, and toxic etiologies. Increased prevalence of non-specific white matter changes in adult population poses challenges during diagnostic considerations. Clinico-radiological spectrum and molecular landscape of adult-onset leukodystrophies have not been completely elucidated at this time. Diagnostic approach is less well-standardized when compared to the childhood counterpart. Absence of family history and reduced penetrance in certain disorders frequently create a dilemma. Comprehensive evaluation and molecular confirmation when available helps in prognostication, early initiation of treatment in certain disorders, enrollment in clinical trials, and provides valuable information for the family for reproductive counseling. In this review article, we aimed to formulate an approach to adult-onset leukodystrophies that will be useful in routine practice, discuss common adult-onset leukodystrophies with usual and unusual presentations, neuroimaging findings, recent advances in treatment, acquired mimics, and provide an algorithm for comprehensive clinical, radiological, and genetic evaluation that will facilitate early diagnosis and consider active treatment options when available. A high index of suspicion, awareness of the clinico-radiological presentations, and comprehensive genetic evaluation are paramount because treatment options are available for several disorders when diagnosed early in the disease course.https://www.frontiersin.org/articles/10.3389/fneur.2023.1219324/fulladult-onset leukodystrophyleukodystrophyleukoencephalopathyneurogeneticsneurometabolic disorder |
| spellingShingle | Karthik Muthusamy Ajith Sivadasan Luke Dixon Sniya Sudhakar Maya Thomas Sumita Danda Zbigniew K. Wszolek Klaas Wierenga Radhika Dhamija Ralitza Gavrilova Adult-onset leukodystrophies: a practical guide, recent treatment updates, and future directions Frontiers in Neurology adult-onset leukodystrophy leukodystrophy leukoencephalopathy neurogenetics neurometabolic disorder |
| title | Adult-onset leukodystrophies: a practical guide, recent treatment updates, and future directions |
| title_full | Adult-onset leukodystrophies: a practical guide, recent treatment updates, and future directions |
| title_fullStr | Adult-onset leukodystrophies: a practical guide, recent treatment updates, and future directions |
| title_full_unstemmed | Adult-onset leukodystrophies: a practical guide, recent treatment updates, and future directions |
| title_short | Adult-onset leukodystrophies: a practical guide, recent treatment updates, and future directions |
| title_sort | adult onset leukodystrophies a practical guide recent treatment updates and future directions |
| topic | adult-onset leukodystrophy leukodystrophy leukoencephalopathy neurogenetics neurometabolic disorder |
| url | https://www.frontiersin.org/articles/10.3389/fneur.2023.1219324/full |
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