Objective: To report baclofen-associated worsening of parkinsonism in a patient with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and recent brainstem infarction, highlighting the need for caution when prescribing baclofen in patients with vulnerable dopaminergic systems.

Background: CADASIL is a hereditary small-vessel disease that can lead to vascular parkinsonism through progressive subcortical damage. Baclofen, a GABA-B receptor agonist commonly used for spasticity and hiccups, has central inhibitory effects that may worsen motor symptoms in patients with impaired dopaminergic pathways.

Method: We describe a 68-year-old man with genetically confirmed CADASIL and baseline vascular parkinsonism who developed a pontine infarction complicated by intractable hiccups. Baclofen was initiated for symptomatic control after other treatments failed. Clinical progression of parkinsonian symptoms was monitored using the Unified Parkinson’s Disease Rating Scale (UPDRS) and Hoehn and Yahr staging. The temporal relationship between baclofen exposure, symptom worsening, and subsequent drug withdrawal was analyzed to assess a possible medication-associated exacerbation of parkinsonism.

Results: A 68-year-old man with CADASIL and baseline vascular parkinsonism, ambulatory with a walker and stable motor symptoms (Unified Parkinson’s Disease Rating Scale [UPDRS] 77, Hoehn and Yahr stage 4), suffered a pontine infarct with new hemiparesis, ophthalmoparesis, and intractable hiccups. Baclofen (10 mg twice a day) was initiated after failed trials of metoclopramide and pregabalin. Within one week, his parkinsonism markedly worsened (UPDRS 84, stage 5), with increased rigidity, bradykinesia, and loss of bed mobility. Discontinuation of baclofen led to partial improvement over five days (UPDRS 80, stage 4). No other etiologies were identified, supporting a probable drug-induced worsening based on temporal association.

Conclusion: This case suggests a probable baclofen-associated worsening of parkinsonism in a patient with CADASIL and recent pontine infarction. The temporal relationship between baclofen initiation and motor deterioration, with partial improvement after withdrawal, supports a drug-related effect. Clinicians should exercise caution when prescribing baclofen in patients with secondary parkinsonism or significant cerebrovascular disease.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/baclofen-induced-worsening-of-parkinsonism-in-a-patient-with-cadasil-and-brainstem-stroke/