Bilateral dentate hyperintensities: Isoniazid-induced toxicity

Clinical History

42-year-old male patient with chronic kidney disease and abdominal tuberculosis presented to emergency with tremors and ataxia. The patient had a history of intake of Anti Tubercular Therapy (ATT) including rifampicin, isoniazid, ethambutol and pyrizinamide for abdominal tuberculosis for 3 months. On neurological examination, the patient had an ataxic gait with dysdiadochokinesia.

Imaging Findings

Magnetic resonance imaging brain revealed symmetric hyperintensity involving bilateral dentate nuclei of the cerebellum on T2 (Fig. 1) and T2 Fluid attenuated inversion recovery (FLAIR) (Fig. 2) sequences. Hyperintensity was seen on diffusion-weighted sequence (Fig. 3) without corresponding restriction on ADC image (Fig. 4). Bilateral dentate nuclei appeared isointense on T1-weighted sequence. No blooming was seen on susceptibility-weighted images to suggest any haemorrhage. There were no tuberculomas, abscesses or hydrocephalus to suggest central nervous system tuberculosis. Mild cerebral atrophic changes were seen with prominence of the cortical sulci and the fissural spaces. A diagnosis of isoniazid-induced cerebellar toxicity was considered and isoniazid (INH) was withdrawn. The patient was started on pyridoxine and ATT regime was modified to include rifampicin, pyrazinamide and levofloxacin. Within two weeks, the patient improved clinically without any neurodeficit. Repeat MRI after 4 weeks revealed complete resolution of bilateral dentate hyperintensities (Fig. 5).

Discussion

INH (Isoniazid) is an antitubercular drug that is known to cause hepatotoxicity as well as neurotoxicity, however, it is considered safe in patients with kidney disease. Neurotoxicity due to INH usually manifests with seizures, encephalopathy and/or peripheral neuropathy. Cerebellar ataxia due to INH is rare [1]. Cerebellitis may occur in patients with chronic kidney disease due to reduced clearance of INH.
The mechanism for INH toxicity is due to energy deprivation and deficiency of Vitamin B complex. There is interruption of pathways responsible for pyridoxine phosphorylation resulting in decreased production of pyridoxal 5-phosphate required for neurotransmission via gamma aminobutyric acid (GABA). GABA is an inhibitory neurotransmitter in the central nervous system. Deficiency of GABA results in cerebellar signs.

On MRI, INH causes symmetrical hyperintensities involving bilateral dentate nuclei [2] due to its toxicity-induced oedema. The diagnosis of INH-induced cerebellitis should be made after ruling out other causes of dentate hyperintensities. Bilateral dentate involvement may occur in patients with enteroviral infections, metronidazole toxicity, methyl bromide toxicity, maple syrup urine disease and atypical Wernicke’s encephalopathy [3, 4, 5].

The role of imaging lies in establishing the diagnosis of cerebellitis in patients taking INH and to distinguish it from neurodeficit due to CNS tuberculosis. The possibility of INH-induced toxicity should be considered in patients on ATT presenting with cerebellar symptoms like ataxia and tremors.

Differential Diagnosis List

Final Diagnosis

Bilateral dentate hyperintensity due to isoniazid toxicity.

URL:	https://www.eurorad.org/case/13907
DOI:	10.1594/EURORAD/CASE.13907
ISSN:	1563-4086