Lorazepam-Induced GABAergic Modulation in Postoperative Pediatric Cerebellar Mutism Syndrome

Case Diagnosis: An 11-year-old male with medulloblastoma developed Postoperative Pediatric Cerebellar Mutism Syndrome (ppCMS) following gross total resection presented with mutism, emotional dysregulation, impaired volitional movement initiation, and ataxia.

Case Description or Program Description: Postoperatively, the patient presented with severe speech and motor deficits. Although no improvement was appreciated with bromocriptine, risperidone, and gabapentin, a transient improvement in mutism and motor initiation was noted following intranasal midazolam (5 mg) during radiation simulation prompted initiation of oral lorazepam (2 mg daily, 0.06 mg/kg). Sustained improvements in speech fluency, spontaneous motor activity, and therapy engagement were observed. Functional assessments revealed a 40-unit gain on WeeFIM within one week, compared to a 1-unit gain the preceding week. Symptom regression following lorazepam discontinuation and recovery upon reintroduction suggested underlying GABAergic dysfunction as a mechanistic factor in ppCMS.

Setting: Pediatric inpatient rehabilitation service.

Assessment/Results: Following lorazepam initiation, significant improvements in speech fluency, motor initiation, and therapy participation occurred with a 40-unit increase in WeeFIM scores within one week, exceeding prior functional improvements. Regression upon medication cessation further validated lorazepam’s therapeutic efficacy. Postoperative MRI showed no residual tumor nor structural lesions, reinforcing the hypothesis of a pathophysiologic basis for ppCMS involving disrupted cerebellothalamocortical networks rather than structural damage. These clinical observations highlight lorazepam’s potential role as a neuromodulatory agent for ppCMS.

Discussion (relevance): This case underscores the therapeutic potential of benzodiazepine-mediated GABAergic modulation in ppCMS management. Lorazepam’s efficacy suggests disrupted inhibitory-excitatory cerebellothalamocortical networks, rather than dopaminergic or serotonergic pathways alone, underpin ppCMS symptomatology. Recognizing ppCMS as a network dysfunction supports pharmacologic interventions targeting inhibitory-excitatory balance. Future research should explore less-sedating benzodiazepines, integrate advanced neuroimaging, and consider neuromodulation strategies, shifting paradigms toward individualized, network-based neurorehabilitation.

Conclusions: Lorazepam-induced GABAergic modulation significantly facilitated recovery of speech and motor function in ppCMS, underscoring its potential as a targeted adjunctive therapy within precision neurorehabilitation for ppCMS.