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Lorazepam for post-operative pediatric cerebellar mutism syndrome: A case report
Son Nguyen1, Denesh Ratnasingam2, Kimberly C Hartman2
1University of Missouri - Kansas City School of Medicine, Kansas City, Missouri, USA.
Abstract:
Case DiagnosisAn 11-year-old male with medulloblastoma underwent gross total resection of a posterior fossa tumor, complicated by post-operative pediatric cerebellar mutism syndrome (ppCMS), exhibiting mutism, emotional dysregulation, impaired volitional movement initiation, and ataxia.Case DescriptionWhile ppCMS's pathophysiology remains incompletely understood, prevailing hypotheses implicate cerebellothalamocortical dysregulation, functional diaschisis, and inhibitory-excitatory network imbalance. This case explores the use of lorazepam, a benzodiazepine that enhances GABA-A receptor activity, as a potential neuromodulator to facilitate recovery in ppCMS.SettingTertiary care children's hospital.Assessments/ResultsPharmacologic trials with bromocriptine, risperidone, and gabapentin yielded minimal benefit. However, administration of intranasal midazolam (5 mg) during radiation simulation resulted in transient resolution of mutism and improved initiation of movement. Based on this response, lorazepam (2 mg daily, 0.06 mg/kg) was initiated, leading to sustained improvements in speech, motor function, and therapy participation. Functional outcome assessments, including the WeeFIM, revealed a 40-unit gain within one week of lorazepam initiation compared to a 1-unit gain in the preceding week. Immediate regression was noted upon medication discontinuation and reintroduction resulted in subsequent recovery.Discussion/RelevanceThe differential response to benzodiazepines compared to other medications suggests potential for inhibitory-excitatory network imbalances. Future research should explore whether less sedating benzodiazepines, such as clobazam, or other GABAergic modulators could provide similar benefits without the cognitive side effects associated with lorazepam.ConclusionsThere is compelling evidence that benzodiazepine-mediated GABAergic modulation may facilitate CMS recovery by restoring cerebellothalamocortical network function. The observed improvements in motor initiation and speech fluency underscore the potential for pharmacologic neuromodulation as an adjunct to traditional rehabilitative therapies.An 11-year-old male with medulloblastoma underwent gross total resection of a posterior fossa tumor, complicated by ppCMS, exhibiting mutism, emotional dysregulation, impaired volitional movement initiation, and ataxia. Amid ongoing neurorehabilitation, a pharmacologic trial with lorazepam led to a reproducible improvement in speech and engagement. Though transient, the response suggested reversible disruption within functional circuits rather than fixed structural damage. This case report uncovers latent functional capacity in ppCMS, which can help distinguish ppCMS from other overlapping neurologic or psychiatric conditions throughout the course of rehabilitation.
Insights
Lorazepam effectively treated pediatric cerebellar mutism syndrome (ppCMS) in an 11-year-old, improving speech and motor function. This suggests benzodiazepines may restore network function for ppCMS recovery.
Area of Science:
- Neuroscience
- Pediatric Neurology
- Pharmacology
Background:
- Post-operative pediatric cerebellar mutism syndrome (ppCMS) is a complex condition following posterior fossa tumor resection, characterized by mutism, emotional dysregulation, and motor deficits.
- The exact pathophysiology of ppCMS is not fully understood but is hypothesized to involve cerebellothalamocortical pathway dysregulation and network imbalances.
Purpose of the Study:
- To investigate the potential of lorazepam, a benzodiazepine, as a neuromodulator to facilitate recovery in a case of ppCMS.
- To explore the role of GABAergic modulation in addressing the neurobiological underpinnings of ppCMS.
Main Methods:
- A case study of an 11-year-old male with medulloblastoma and subsequent ppCMS.
- Pharmacologic trials including bromocriptine, risperidone, gabapentin, and benzodiazepines (midazolam and lorazepam).
- Assessment of functional outcomes using the WeeFIM scale and clinical observation of speech and motor function.
Main Results:
- Initial trials with other medications showed minimal benefit.
- Intranasal midazolam provided transient improvement in mutism and motor initiation.
- Lorazepam administration led to sustained improvements in speech, motor function, and therapy participation, with a significant gain on the WeeFIM scale.
- Medication withdrawal resulted in regression, while reintroduction led to recovery, indicating a reproducible effect.
Conclusions:
- Benzodiazepine-mediated GABAergic modulation may be a viable therapeutic strategy for ppCMS by potentially restoring cerebellothalamocortical network function.
- Pharmacologic neuromodulation with lorazepam can serve as an adjunct to traditional rehabilitation therapies for ppCMS.
- This case highlights the potential for reversible functional disruption in ppCMS and the utility of targeted pharmacologic interventions.
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