Department of Neurology, Thanjavur Medical College, Thanjavur, Tamil Nadu, India

*Corresponding author:Ramachandran Mohan Raj, Department of Neurology, Thanjavur Medical College, Thanjavur, Tamil Nadu, India. E-mail Id: mrama248@gmail.com

Article Information:Submission: 09/01/2025; Accepted: 10/02/2025; Published: 15/02/2025

Copyright: © 2025 MohanRaj R, et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Neurological manifestations of chronic kidney disease are due to various reasons and one among them is inefficient elimination of toxins by the kidneys. The neurological manifestations can involve both central and peripheral nervous systems. It ranges from severe encephalopathy, coma to sensorimotor peripheral neuropathy. However, cerebellar manifestations in CKD per se is rare, though it can occur if any predisposing factors are there. Here, we report a case of acute pan-cerebellar syndrome in newly diagnosed CKD patient who took isoniazid prophylaxis for contact with open tuberculosis.

Keywords:Chronic Kidney Disease; Cerebellar Syndrome; Isoniazid

Chronic Kidney Disease is associated with several neurological manifestations. It includes progressive cognitive decline, peripheral neuropathy, movement disorders, sleep disturbance, delirium, seizures,and metabolic encephalopathy leading to coma and death. Postulated mechanisms for these manifestations are due to accumulation of toxic organic acids in the CNS or to direct effects on the CNS of parathyroid hormone. But there are no direct cerebellar manifestations in CKD unless there are some predisposing factors.

Among anti-tubercular drugs, Isoniazid is known for its neurotoxicity and hepatotoxicity. Neurotoxicity generally manifests as peripheral neuropathy which is usually mild and reversible. In this report, we present a newly diagnosed CKD patient who developed rare central nervous system complication following isoniazid prophylaxis.

A 60-year-old-woman admitted in our intensive care unit with history of giddiness for 2 days followed by vomiting and acute onset of slurring of speech, unsteadiness while sitting and walking with excessive sleepiness since the night before the day of admission. There was no history of fever, diarrhea, headache, visual disturbance, and motor weakness. No history of seizures altered sensorium and loss of consciousness. She didn’t have any significant past medical and surgical history. She took isoniazid prophylaxis for 5days, started to her because her husband was recently diagnosed to have sputum positive pulmonary tuberculosis.

On examination, patient was drowsy, arousable to call and oriented to time, place, and person. She obeyed all commands. Her vitals were stable with mild hypertension (admission BP was 150/90mmHg). On neurological examination, she was drowsy

and arousable to call and oriented to time, place, and person. Her language was normal with cerebellar type of dysarthria.Cranial nerve examinations showed normal fundus with no extra-ocular movement abnormalities. Motor power was normal and sensory examinations were also normal. No evidence of extra-pyramidal and autonomic involvement. She had gross stance and gait ataxia with impaired rapid alternative movements and incoordination in both upper and lower limbs.There were no generalized lymphadenopathies, pedal edema, or hepatosplenomegaly. Breast examination was normal. Clinically she was suspected to have posterior circulation stroke with localisation to pancerebellar involvement and hence the treatment was started for the same.

She was evaluated for above mentioned complaints and findings. Her complete blood count showed hemoglobin of 9.5g/ dl, total leucocyte count of 10,930/cu.mm and platelet count of 2.23L/cu.mm. The renal function tests revealed serum urea of 75mg/dl and creatinine of 2.9mg/dl with creatinine clearance of 16ml/min and eGFR of 18ml/min/1.73m2. The serum sodium was 142mmol/l and serum potassium were 3.7mmol/l. Ultrasound abdomen showed bilateral contracted kidney. CT abdomen showed also showed bilateral contracted kidney. CT chest was normal. Electrocardiogram and Echocardiogram was normal. Her CSF analysis were unremarkable with JE negative. Serum JE, IgM dengue, IgM Scrub typhus and CBNAAT were also negative.

Neuroimaging namely MRI of Brain was carried out which showed bilateral symmetrical T2/FLAIR hyperintensities in dentate nucleus and thalamus with mild diffusion restrictions and rest of the brain parenchyma was normal. MR angiogram and venogram was also normal. Carotid-vertebral artery doppler was also normal.

As there were no other etiologies for acute onset pancerebellar syndrome, patient was re-questioned about the count of tablets of INH taken and she broke the ice with history of intake of isoniazid tablets of 100mg each for 3times a day for 5days prior to admission. Through the process of diagnosis of exclusion, we made the possible diagnosis of isoniazid induced cerebellar toxicity, which is also described in literature especially in CKD patients. Patient improved in a week time after treatment with high dose pyridoxine [1-5].

Isoniazid is the first line anti-tubercular drug with bactericidal activity. The usual dose in the fixed dose combination of current ATT regimen is 75mg. INH interferes with pyridoxine metabolism resulting in deficiency of this vitamin. Adverse effects due to INH occur in 5% of patients even with adequate dose of pyridoxine supplementation. The most common Neurological Adverse Drug reaction of INH is that of sensorimotor peripheral neuropathy which is mild and usually reversible. Due to its metabolism in liver, no dosage adjustment is needed for patients with renal disease. It is well tolerated in CKD patients and when toxicity occurs, it is related to hepatotoxicity.

CNS toxicity due to INH and its metabolite isonicotinylhydrazide, causing encephalopathy and seizures has been documented, but cerebellar manifestations are very rare. Cerebellar toxicity occurs due to reduced GABA and down regulation of NMDA receptors, with resultant edema of the dentate nucleus. Since the main route of elimination of INH is through kidneys, in CKD patients, there is high chance of accumulation of its toxic metabolite and causing neurotoxicity.

Neuroimaging findings in INH induced cerebellitis include bilateral symmetrical T2/FLAIR hyperintensities in dentate nucleus because of edema. Similar imaging findings are document in metronidazole toxicity, arboviral and enteroviral infections, maple syrup urine disease and metabolic disorders like Wernicke’s encephalopathy and hypoparathyroidism. In our patient, it is not isolated involvement of dentate nucleus but also thalamus and midbrain involved which rare in INH toxicity.

Association between initiation of therapy and onset of symptoms should give us the diagnosis of INH toxicity related cerebellitis.

INH induced cerebellar toxicity should be kept in differential diagnosis in the case of bilateral dentate nucleus hyperintensities, though metronidazole is the common one. In the background of renal impairment, INH can cause cerebellar syndrome apart from other CNS manifestations. Early diagnosis and intervention like dose modification and pyridoxine supplementations will preventive morbidity.