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Published on: August 9, 2024
Cerebellar Transcranial Magnetic Stimulation Improves Ataxia in Minamata Disease
Masaaki Nakamura1, Masafumi Bekki2, Youko Miura1
1Department of Clinical Medicine, National Institute for Minamata Disease, Kumamoto, Japan.
Abstract:
Minamata disease (MD) is a form of intoxication involving the central nervous system and is caused by ingesting seafood from methylmercury-contaminated areas in Japan. In MD, cerebellar ataxia is a cardinal feature observed in approximately 80% of MD patients. Although cerebellar transcranial magnetic stimulation (TMS) has recently been used for treating cerebellar ataxia, the optimal stimulation conditions remain unclear. Here, we report the first case of cerebellar ataxia in an MD patient that was significantly improved after high-frequency cerebellar TMS. To determine the optimal stimulation conditions, we examined the excitability of the primary motor cortex (M1) using resting-state functional magnetic resonance imaging (rs-fMRI). rs-fMRI revealed M1 hyperconnectivity, which was indicative of activation of the dentato-thalamo-cortical (DTC) pathway. Thus, high-frequency cerebellar TMS was applied to inhibit the DTC pathway. Improvement of cerebellar ataxia was only observed after real TMS, not sham stimulation. As this effect was consistent with inhibition of hyperconnectivity of M1, the effectiveness of high-frequency cerebellar TMS for cerebellar ataxia was thought to be caused by inhibition of the DTC pathway. Therefore, we suggest that the evaluation of M1 excitability using rs-fMRI can be effective for determining the optimal TMS stimulation conditions for cerebellar ataxia.
Insights
High-frequency cerebellar transcranial magnetic stimulation (TMS) significantly improved Minamata disease (MD) related cerebellar ataxia. This treatment appears to work by inhibiting the dentato-thalamo-cortical pathway, as confirmed by brain imaging.
Area of Science:
- Neuroscience
- Neurology
- Toxicology
Background:
- Minamata disease (MD) is a severe central nervous system intoxication caused by methylmercury poisoning, often leading to cerebellar ataxia in about 80% of patients.
- Cerebellar ataxia is a debilitating condition affecting motor control and coordination.
- Current treatments for cerebellar ataxia, including cerebellar transcranial magnetic stimulation (TMS), lack clearly defined optimal stimulation parameters.
Observation:
- This study reports the first case of significant improvement in cerebellar ataxia in a Minamata disease patient following high-frequency cerebellar TMS.
- Resting-state functional magnetic resonance imaging (rs-fMRI) was used to assess primary motor cortex (M1) excitability.
- rs-fMRI revealed M1 hyperconnectivity, suggesting activation of the dentato-thalamo-cortical (DTC) pathway.
Findings:
- High-frequency cerebellar TMS was applied to specifically inhibit the identified hyperactive DTC pathway.
- Significant improvement in cerebellar ataxia was observed exclusively with real TMS, not sham stimulation.
- The observed clinical improvement correlated with the inhibition of M1 hyperconnectivity, supporting the proposed mechanism of action.
Implications:
- High-frequency cerebellar TMS shows promise as an effective treatment for cerebellar ataxia in Minamata disease patients.
- Using rs-fMRI to evaluate M1 excitability may help personalize and optimize TMS treatment protocols for cerebellar ataxia.
- This approach could potentially be extended to other conditions involving cerebellar dysfunction and ataxia.
