The Clinical Concept of LTDpathy: Is Dysregulated LTD Responsible for Prodromal Cerebellar Symptoms?
Abstract
:1. Introduction
2. Dysregulated LTD and Immune-Mediated Cerebellar Ataxia
3. Dysregulated LTD and Degenerative Cerebellar Ataxia
3.1. Prodromal Stage in SCA
3.2. SCA1
3.3. SCA3
3.4. SCA6
3.5. Dysregulated LTD Preceding Cell Death
4. Conclusions: Definition of LTDpathy and its Clinical Significance
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- LTDpathy is a clinical spectrum comprising etiologies characterized by impairments of the PF-PC LTD and related to adaptative behaviors such as VOR, blink reflex, and prism adaptation;
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- LTDpathy includes CA of immune origin associated with anti-VGCC, anti-mGluR1, and anti-GluR delta Abs as well as of genetic origins such as SCA1, 3, and 6.
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- In paraneoplastic IMCAs or SCA characterized by persistent impairments of a wide range of molecular mechanisms, these functional disorders are followed by degenerative cell processes;
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- In such cases, PF-PC LTD-related maladaptive symptoms are one of the prodromal symptoms. However, these adaptive behavior disorders are difficult to notice for clinicians (subtle symptoms) in routine neurological examinations;
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- In such conditions, impairment of PF-PC LTD and related adaptative behaviors can be promising biomarkers for early intervention. Early intervention is necessary during the period when cerebellar reserve, defined as the capacity for compensation and restoration pathologies, is preserved [43].
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Anti-VGCC | Anti-mGluR1 | Anti-GluR Delta | |
---|---|---|---|
Prevalence in IMCAs | Sometimes | Rare | Rare |
Trigger of autoimmunity | Mainly with paraneoplasia (SCLC, prostate adenocarcinoma, non-Hodgkin’s lymphoma). A few without associated cancer | Some with paraneoplasia (Hodgkin’s lymphoma, prostate adenocarcinoma). Others infrction or without paraneoplasia | Infection, vaccination |
Median age, predominant sex | 60s, Male (>95%) | 50s, Male (57%) | Children |
Features of CAs | Pan-cerebellar ataxias | Gait and limb ataxias | Gait ataxia, sometimes associated with limb ataxia and dysarthria |
MRI | Variable: From none to mild atrophy | Variable: From none to mild atrophy | No atrophy |
Therapeutic outcomes | Paraneoplasia: Variable. From good to poor response to IVIg, prednisone, and mycophenolate mofetil (Full or partial recovery 8%, stabilization 50%, and persistent worsening 42%). Without paraneoplasia: Improvement reported. | Paraneoplasia: Variable. From good to poor response to IVIg, PE. Without paraneoplasia: Generally good response to IVIg, steroid, mycophenolate, and rituximab. (Full recovery 40%, mild recovery and stabilization 52%, and persistent worsening 8%). | Generally good response to IVIg or IVMP (Full or partial recovery 67%, stabilization 33%, and persistent worsening 0%). |
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Mitoma, H.; Yamaguchi, K.; Honnorat, J.; Manto, M. The Clinical Concept of LTDpathy: Is Dysregulated LTD Responsible for Prodromal Cerebellar Symptoms? Brain Sci. 2022, 12, 303. https://doi.org/10.3390/brainsci12030303
Mitoma H, Yamaguchi K, Honnorat J, Manto M. The Clinical Concept of LTDpathy: Is Dysregulated LTD Responsible for Prodromal Cerebellar Symptoms? Brain Sciences. 2022; 12(3):303. https://doi.org/10.3390/brainsci12030303
Chicago/Turabian StyleMitoma, Hiroshi, Kazuhiko Yamaguchi, Jerome Honnorat, and Mario Manto. 2022. "The Clinical Concept of LTDpathy: Is Dysregulated LTD Responsible for Prodromal Cerebellar Symptoms?" Brain Sciences 12, no. 3: 303. https://doi.org/10.3390/brainsci12030303
APA StyleMitoma, H., Yamaguchi, K., Honnorat, J., & Manto, M. (2022). The Clinical Concept of LTDpathy: Is Dysregulated LTD Responsible for Prodromal Cerebellar Symptoms? Brain Sciences, 12(3), 303. https://doi.org/10.3390/brainsci12030303