Baclofen Neurotoxicity: A Metabolic Encephalopathy Susceptible to Exacerbation by Benzodiazepine Therapy (P6.356)

Background: Baclofen, a gamma-aminobutyric acid derivative, is commonly used in the treatment of spasticity. Baclofen toxicity can produce an encephalopathy sometimes associated with myoclonus and seizures. Associated EEG abnormalities include generalized slowing, and periodic triphasic complexes and sharp waves that have been reported as non-convulsive status epilepticus (NCSE). Methods: Baclofen toxicity was defined as an encephalopathy in the setting of baclofen use and without other identifiable cause. Patients with baclofen toxicity were identified from an EEG database, and their clinical and EEG findings analysed. Results: 13 patients were identified, aged 29 to 81 years. All were receiving oral baclofen in doses ranging from 10mg to 200mg daily, most commonly for spasticity (10 patients). All patients were confused, 11 with reduced consciousness and 4 requiring intubation. 5 patients had myoclonus, 2 of whom also had tonic-clonic seizures. All patients had abnormal EEGs. 12 patients had moderate-to-severe generalized slowing. 8 patients had generalized, bisynchronous triphasic sharp waves occurring at 1-2 Hz , sometimes with an anterior to posterior phase lag. Three patients received small doses of intravenous midazolam or diazepam, in all cases resulting in marked depression of consciousness and respiration, and without any subsequent improvement in the conscious state. Suppression of periodic complexes and all EEG activity following intravenous midazolam was confirmed in one patient, having continuous EEG monitoring. Baclofen was discontinued in all patients. Serial plasma Baclofen levels were measured in 2 patients. Falling levels mirrored clinical and electrophysiological improvement. Conclusions: Baclofen toxicity can produce an acute encephalopathy even at modest doses. When present, periodic sharp triphasic complexes on EEG are a manifestation of a toxic encephalopathy rather than NCSE. These patients exhibit a marked vulnerability to the depressant effects of benzodiazepines, even at small doses. Improvement follows a time course consistent with the period required for baclofen clearance. Disclosure: Dr. Triplett has nothing to disclose. Dr. Lawn has nothing to disclose. Dr. Dunne has nothing to disclose.