Frontal Lobe Syndrome Following Baclofen Use in a Patient with Chronic Kidney Disease on Hemodialysis

Abstract How to cite this article:
Tharakan A. Frontal Lobe Syndrome Following Baclofen Use in a Patient with Chronic Kidney Disease on Hemodialysis. Saudi J Kidney Dis Transpl 2022;33:216-7
How to cite this URL:
Tharakan A. Frontal Lobe Syndrome Following Baclofen Use in a Patient with Chronic Kidney Disease on Hemodialysis. Saudi J Kidney Dis Transpl [serial online] 2022 [cited 2023 Jan 17];33:216-7. Available from: https://www.sjkdt.org/text.asp?2022/33/1/216/367819

To the Editor,

A 65-year-old female with chronic kidney disease, on regular maintenance hemodialysis (HD), was prescribed tablet baclofen 10 mg orally three times daily for intractable hiccups by a physician. After three days, she presented to the emergency department with altered sensorium and quadriparesis. She had taken five tablets by that time which came to a total of 50 mg of baclofen. She had a power of 2/5 in all limbs and hypotonia with absent reflexes. She had fluent aphasia with perseveration of speech and confabulation. She kept repeating a particular phase and described events that her family members refuted. She did not have respiratory distress. Her blood pressure was 160/90 mm Hg, heart rate 70/min, and SpO2s 96%. Baseline investigations, including hemoglobin, total white cell count, blood sugar, and serum electrolytes were normal. Considering the sequence of events, she was suspected to have baclofen-induced neurotoxicity. Baclofen was withheld, and she was given two sessions of HD on consecutive days following which her sensorium and power returned to normal, and she was discharged to continue HD on a regular basis. Since she improved with HD further investigations, including brain imaging, electroencephalogram and baclofen drug levels were not done.

Baclofen is a centrally acting gammaaminobutyric acid agonist generally used for relieving muscle spasticity and intractable hiccups. It is primarily excreted by the renal route[1] and there is dose accumulation in renal failure. Therefore it comes as no surprise that its toxicity becomes manifest in patients with worsening renal failure, especially those on dialysis. The therapeutic dosage range of baclofen is between 15 mg and 60 mg per day, but there have been reports of baclofen toxicity in patients with severe renal failure at dosages as low as 5 mg/day.[2] Acute baclofen toxicity presents with encephalopathy, respiratory depression, muscle hypotonia, hyporeflexia, and cardiac conduction abnormalities. Baclofen has a low molecular weight with relatively low protein binding and volume of distribution. Hence HD has been found to be effective in removing baclofen from the body.[3]

The frontal lobes are required for higher-functioning processes such as language, speech, behavior, planning, and motivation. Frontal lobe impairment causes various features such as abulia, lack of insight, inappropriate jocularity, confabulation, perseveration, memory disturbances, sexual disinhibition, and akinetic mutism.[4] Some of the causes of frontal lobe syndrome are trauma, tumor, infection, cerebrovascular events, and degenerative disorders. Liu et al[5] described a patient with baclofen toxicity manifesting with frontal lobe syndrome who developed paraphasia, euphoric mood, and prominent perseverative behavior with flaccid paraplegia after taking seven doses of 10 mg of baclofen thrice daily. Our case had somewhat similar manifestations.

Baclofen should be given very cautiously in patients with renal impairment and preferably avoided in patients with end-stage renal disease, as even low doses have been reported to precipitate neurotoxicity in these susceptible patients.

Conflict of interest: None declared.

References

1.Wuis EW, Dirks MJ, Termond EF, Vree TB, Van der Kleijn E. Plasma and urinary excretion kinetics of oral baclofen in healthy subjects. Eur J Clin Pharmacol 1989;37:181-4.

2.Chen KS, Bullard MJ, Chien YY, Lee SY. Baclofen toxicity in patients with severely impaired renal function. Ann Pharmacother 1997;31:1315-20.

3.Wu VC, Lin SL, Lin SM, Fang CC. Treatment of baclofen overdose by haemodialysis: A pharmacokinetic study. Nephrol Dial Transplant 2005;20:441-3.

4.Reber J, Tranel D. Frontal lobe syndromes. In: D'Esposito M, Grafman JH, Editors. Handbook of Clinical Neurology. Vol. 163.: Elsevier; 2019. p. 147-64.