ArticleNeurology2021
Systematic Analysis of Brain MRI Findings in Adaptor Protein Complex 4-Associated Hereditary Spastic Paraplegia.
Article in Neurology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 28 citations in OpenAlex.
- CRISPR/Cas9 loss-of-function screen in a neuronal model of AP-4 deficiency identifies ATG9A trafficking modulators.JCI insight · 2026Article
- Diagnostic Utility of the ATG9A Ratio in AP-4-Associated Hereditary Spastic Paraplegia.Annals of clinical and translational neurology · 2026Article
- Hereditary Spastic Paraplegy Associated with the AP4S1 Gene: A Case Series Highlighting Diagnostic Pitfalls and Phenotypic Variability.Molecular syndromology · 2025Article
- Fetal and Perinatal Brain MRI Findings in Adaptor Protein Complex 4-Associated Hereditary Spastic Paraplegia.Annals of the Child Neurology Society · 2025Article
- "Ears of the Lynx" Sign on Brain MRI in Siblings With Spastic Paraplegia: A Case Report.Annals of the Child Neurology Society · 2025Article
- Heterozygous variants in AP4S1 are not associated with a neurological phenotype.Annals of clinical and translational neurology · 2025Article
- Altered tubulin detyrosination due to SVBP malfunction induces cytokinesis failure and senescence, underlying a complex hereditary spastic paraplegia.Aging cell · 2025Article
- An update on autophagy disorders.Journal of inherited metabolic disease · 2025Review
- Pre-clinical development of AP4B1 gene replacement therapy for hereditary spastic paraplegia type 47.EMBO molecular medicine · 2024Article
- Imaging Findings and MRI Patterns in a Cohort of 18q Chromosomal Abnormalities.AJNR. American journal of neuroradiology · 2024Article
- AAV gene therapy for hereditary spastic paraplegia type 50: a phase 1 trial in a single patient.Nature medicine · 2024Article
- High-content screening identifies a small molecule that restores AP-4-dependent protein trafficking in neuronal models of AP-4-associated hereditary spastic paraplegia.Nature communications · 2024Article
- Plasma Neurofilament Light Chain Is Elevated in Adaptor Protein Complex 4-Related Hereditary Spastic Paraplegia.Movement disorders : official journal of the Movement Disorder Society · 2023Article
- Exome Sequencing and the Identification of New Genes and Shared Mechanisms in Polymicrogyria.JAMA neurology · 2023Article
- Intrathecal AAV9/AP4M1 gene therapy for hereditary spastic paraplegia 50 shows safety and efficacy in preclinical studies.The Journal of clinical investigation · 2023Article
- The clinical and molecular spectrum of ZFYVE26-associated hereditary spastic paraplegia: SPG15.Brain : a journal of neurology · 2023Article
- Putative founder effect of Arg338* AP4M1 (SPG50) variant causing severe intellectual disability, epilepsy and spastic paraplegia: Report of three families.Clinical genetics · 2023Article
- Lunapark deficiency leads to an autosomal recessive neurodevelopmental phenotype with a degenerative course, epilepsy and distinct brain anomalies.Brain communications · 2023Article
- Blended Phenotype of Prader-Willi Syndrome and HSP-Neurology. Genetics · 2022Article
- Phenotypic Variability with Two Novel Variants in SPG15: Catching the Lynx by its Ears.Movement disorders clinical practice · 2022Article
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
BACKGROUND AND
objectivesAP-4-associated hereditary spastic paraplegia (AP-4-HSP: SPG47, SPG50, SPG51, SPG52) is an emerging cause of childhood-onset hereditary spastic paraplegia and mimic of cerebral palsy. This study aims to define the spectrum of brain MRI findings in AP-4-HSP and to investigate radioclinical correlations.
methodsWe performed a systematic qualitative and quantitative analysis of 107 brain MRI studies from 76 individuals with genetically confirmed AP-4-HSP and correlation with clinical findings including surrogates of disease severity.
resultsWe define AP-4-HSP as a disorder of gray and white matter and demonstrate that abnormal myelination is common and that metrics of reduced white matter volume correlate with severity of motor symptoms. We identify a common diagnostic imaging signature consisting of (1) a thin splenium of the corpus callosum, (2) an absent or thin anterior commissure, (3) characteristic signal abnormalities of the forceps minor ("ears of the grizzly sign"), and (4) periventricular white matter abnormalities. The presence of 2 or more of these findings has a sensitivity of ∼99% for detecting AP-4-HSP; the combination of all 4 is found in ∼45% of cases. Compared to other HSPs with a thin corpus callosum, the absent anterior commissure appears to be specific to AP-4-HSP. Our analysis identified a subset of patients with polymicrogyria, underscoring the role of AP-4 in early brain development. These patients displayed a higher prevalence of seizures and status epilepticus, many at a young age. DISCUSSION: Our findings define the MRI spectrum of AP-4-HSP, providing opportunities for early diagnosis, identification of individuals at risk for complications, and a window into the role of the AP-4 complex in brain development and neurodegeneration.
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Registered trials
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