Case Presentation: A 64-year-old male with a medical history of left-occipital stroke and alcohol use disorder presented with progressively worsening dizziness & weakness of his extremities ongoing for six months. The complaints were associated with numbness of fingertips and toes with gait instability resulting in repeated falls. He correlated the symptoms with starting baclofen (taking 160-200mg/day). He endorsed drinking 3-4 glasses of wine daily (for 30 years) with a recent increase in intake. On examination, he had a wide-based gait, his initial labs, urine-toxicology and neurological imaging were unremarkable.On admission, the differential diagnosis for the weakness was Wernicke’s Encephalopathy (WE) vs. Alcohol Withdrawal (AW). Suspicion for WE was low, given lack of oculomotor dysfunction, no T2 FLAIR hyperintensities on MRI, and normal thiamine levels. On day 3, he was somnolent, confused, and disoriented, with periodic checks revealing waxing and waning pattern of alertness.Repeat imaging studies and electroencephalogram did not reveal mass effect, infarct or seizures. Electromyography was not suggestive of Acute Inflammatory demyelinating polyneuropathy.The possibility of withdrawal from baclofen was considered, and the medication was reintroduced. On day 7, although the patient’s mental status improved significantly, he spiked fevers to 101F. Lab work revealed markedly elevated ESR and CRP with negative blood & urine cultures. Lumbar puncture revealed elevated protein 204.8 mg/dL (0-40 mg/dL). The rest of the parameters, including cultures and viral panel, were negative, suggesting aseptic meningitis (ASM). In the absence of other etiologies, ASM due to baclofen use was considered, and the baclofen was gradually tapered and discontinued. The patient’s mental status progressively improved, and his presenting complaints resolved.

Discussion: Baclofen, an analog of the neurotransmitter gamma-aminobutyric acid (GABA), acts at the level of the brain and spinal cord. It is approved by the FDA for the treatment of spasticity from spinal cord lesions and multiple sclerosis. Baclofen is used off-label to maintain alcohol abstinence and treatment of AW, with numerous studies that support and contradict the rationale behind it.Acute baclofen toxicity manifests as delirium, hallucinations, impaired consciousness, autonomic disorders, neuromuscular and respiratory depression, whereas chronic toxicity can manifest as hallucinations, impaired memory, catatonia and acute mania.Baclofen withdrawal can present with visual, auditory, tactile hallucinations, delusions, fluctuating consciousness, fever, and hyperthermia.Although cases of aseptic meningitis after intrathecal administration of baclofen have been reported, cases of aseptic meningitis after oral baclofen use are rare. Our patient presented with symptoms consistent with baclofen toxicity and developed manifestations of withdrawal during the hospital course with evidence of ASM on CSF studies. A comprehensive evaluation for nutritional, infectious, and inflammatory causes was negative, and the diagnosis was established with observed clinical improvement on restarting the baclofen and slowly tapering it.

Conclusions: It is important to consider withdrawal from off-label medications and identify clinical presentations early. Although rare, ASM from oral baclofen should be included among the differentials in cases such as the one presented above.