Baclofen-induced Encephalopathy Research Articles

Low-Dose Baclofen-Induced Encephalopathy in a Patient with End-Stage Renal Disease: A Case Report

Baclofen, a gamma-aminobutyric acid-B receptor agonist, is commonly used for central-origin muscle spasticity and spasm and neuropathic pain. Baclofen toxicity has been reported to cause a range of symptoms including drowsiness, confusion, respiratory depression, seizures, and even coma, particularly with dosage significantly exceeding therapeutic levels. Given that the baclofen is predominantly eliminated through the kidneys, patients with renal failure are at substantial risk for neurotoxic effects. We report a case of baclofen-induced encephalopathy in a patient with end-stage renal disease, characterized by an altered mental state with myoclonus following the consumption of a low dose of baclofen.

Baclofen-induced Encephalopathy in Patients with End-stage Kidney Disease – A Case Series

Introduction/Background: Baclofen is a centrally acting GABA B receptor agonist, widely used for the treatment of neurological diseases ranging from hiccups to multiple sclerosis. As the drug is mainly renally excreted, intoxication can rapidly develop in those patients with a reduced glomerular filtration rate. A strong index of clinical suspicion is essential to correctly diagnose the condition. Case Presentation: We report a case series of patients with advanced kidney disease and baclofen-induced encephalopathy that settled with discontinuation of the drug and hemodialysis sessions. Conclusion: We report this cluster of patients with baclofen toxicity to highlight the common occurrence of neurotoxicity after its use in patients with end-stage renal disease and its resolution after cessation of the drug and hemodialysis sessions.

Baclofen Induced Encephalopathy in Patients with Chronic Kidney Disease

Hiccups are manifestation of uremic syndrome. Baclofen had been used in uremic hiccups, but its usage has been described in literature with development of neurotoxicity in patients with renal failure. The case series reports three patients of Chronic Kidney Disease (CKD) that were on haemodialysis. All of them had intractable hiccups, for which Baclofen was administered. They developed encephalopathy within 24-48 hours of ingestion of Baclofen. The drug was discontinued and the patients improved within 36-48 hours. They were finally discharged with no residual neurological deficit.

Baclofen-induced neurotoxicity in patients with compromised renal function: Review

Baclofen is a centrally-acting γ-amino butyric acid agonist used mainly in the symptomatic management of spasticity originating from the spinal cord. It is absorbed completely from the gastrointestinal tract, metabolized by the liver to a minor degree, and excreted unchanged by the kidneys. Baclofen is moderately lipophilic and can cross the blood-brain barrier easily. At the usual dosage, it acts mainly at the spinal level without central nervous system (CNS) side effects. During renal failure, however, the elimination of the drug will decrease with a prolonged half-life, resulting in a larger area-under-the-curve exposure and disproportionate CNS toxicity. Clinically, these patients with renal failure may present with a variety of toxic symptoms manifesting at therapeutic/sub-therapeutic doses of baclofen. In cases of unexplained mental status changes in a patient receiving baclofen therapy, a careful assessment of renal function and a high suspicion of baclofen-induced encephalopathy will be key to the diagnosis. .

Baclofen-induced encephalopathy in overdose – Modeling of the electroencephalographic effect/concentration relationships and contribution of tolerance in the rat

Baclofen, a γ-amino-butyric acid type-B receptor agonist with exponentially increased use at high-dose to facilitate abstinence in chronic alcoholics, is responsible for increasing poisonings. Baclofen overdose may induce severe encephalopathy and electroencephalographic (EEG) abnormalities. Whether prior prolonged baclofen treatment may influence the severity of baclofen-induced encephalopathy in overdose has not been established. We designed a rat study to characterize baclofen-induced encephalopathy, correlate its severity with plasma concentrations and investigate the contribution of tolerance.Baclofen-induced encephalopathy was assessed using continuous EEG and scored based on a ten-grade scale.Following the administration by gavage of 116 mg/kg baclofen, EEG rapidly and steadily impaired resulting in the successive onset of deepening sleep followed by generalized periodic epileptiform discharges and burst-suppressions. Thereafter, encephalopathy progressively recovered following similar phases in reverse. Periodic triphasic sharp waves, non-convulsive status epilepticus and even isoelectric signals were observed at the most critical stages. Prior repeated baclofen administration resulted in reduced severity (peak: grade 7 versus 9; peak effect length: 382 ± 40 versus 123 ± 14 min, P = 0.008) and duration of encephalopathy (18 versus > 24 h, P = 0.0007), supporting the acquisition of tolerance. The relationship between encephalopathy severity and plasma baclofen concentrations fitted a sigmoidal Emax model with an anticlockwise hysteresis loop suggesting a hypothetical biophase site of action. The baclofen concentration producing a response equivalent to 50% of Emax was significantly reduced (8947 μg/L, ±11.3% versus 12,728 μg/L, ±24.0% [mean, coefficient of variation], P = 0.03) with prior prolonged baclofen administration.In conclusion, baclofen overdose induces early-onset and prolonged marked encephalopathy that is significantly attenuated by prior repeated baclofen treatment. Our findings suggest a possible role for the blood-brain barrier in the development of tolerance; however, its definitive involvement remains to be demonstrated.

Baclofen-Induced Encephalopathy in End Stage Renal Disease.

Baclofen is a highly used centrally acting GABA agonist that continues to be an effective therapy for spasticity and chronic hiccups. The renally dependent excretion determines the circulating concentrations and guides effective dosing to decrease adverse reactions. Caution should be considered in administering baclofen to patients with decreased renal function. We present a patient with end stage renal disease on hemodialysis with recent baclofen ingestion who presented with toxic encephalopathy that was resolved with additional dialysis sessions.

Two Cases of Baclofen-Induced Encephalopathy in Hemodialysis and Peritoneal Dialysis Patients

Hiccups are a spasmodic contraction of the diaphragm and usually transient phenomenon that affects nearly everyone. When hiccups develop, the patients are administrated antispastic agent, such as balcofen. Baclofen is widely used for the treatment of this spastic movement disorders. Also, baclofen is a gamma-aminobutyric acid (GABA) derivative that induces presynaptic motor neuron inhibition and produces a central antispastic response. Baclofen toxicity is rare and has been reported with intrathecal pump and orally administered baclofen, particularly in patients with poor renal function. Herein, we report two cases of encephalopathy in hemodialysis and peritoneal dialysis patients who received low doses of baclofen for persistent hiccups. We suggest that, in patients with chronic kidney disease (CKD), baclofen should be avoided or started at a low dose. If the renal insufficiency patient develops toxic baclofen-induced encephalopathy, hemodialysis may be the proper treatment to improve clinical symptoms.

Two Cases of Baclofen-Induced Encephalopathy in Hemodialysis and Peritoneal Dialysis Patients

Two Cases of Baclofen-Induced Encephalopathy in Hemodialysis and Peritoneal Dialysis Patients

Baclofen-induced encephalopathy in patient with end stage renal disease: Two case reports

We report two end stage renal disease (ESRD) patients, who rapidly developed neurotoxicity after taking baclofen, a centrally acting gamma-aminobutyric acid agonist. They presented to our hospital in a state of confusion. On physical examination, there were no focal neurological deficits and the remainder of the examination was also not diagnostic. Laboratory data were unremarkable. The consciousness improved with supportive treatment and intensive hemodialysis over 3-4 days. In conclusion, physicians should be aware of the possibility of baclofen-induced neurotoxicity in patients with renal disease, especially in ESRD patients and it is necessary to avoid or reduce baclofen dosage in these patients.

Electroencephalographic abnormalities in baclofen-induced encephalopathy

We report a patient in whom the characteristic electroencephalographic features of baclofen intoxication are highlighted and emphasize the role of electrographic abnormalities in the diagnosis of this condition.