TACROLIMUS OR SOMETHING MORE? A DIAGNOSTIC CHALLANGE REVEALING PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY

The clinical spectrum of neurological problems in HIV-positive individuals is broad and includes viral neurotropism, opportunistic infections, cancers, and the immunosuppressive condition brought on by HIV and its therapy. Progressive multifocal leukoencephalopathy (PML), a silent invader of the central nervous system, frequently presents as vague neurocognitive decline or motor impairment, is caused by reactivation of the JCV. In most cases, JCV remains latent in the kidneys and lymphoid organs but can reactivate on the background of immunosuppression. The combination of opportunistic virus, iatrogenic immunosuppression and HIV infection creates ideal condition where the dormant virus finds fertile grounds to infiltrate the brain, and undermine the integrity of the nervous system.

 A middle-aged man had a history of Pelvico-Ureteric Junction Obstruction complicated by a malfunction kidney and secondary FSGS 10 years ago, for which he underwent LRRTX (Live Related Renal Transplant from his brother). Triple immunosuppressants were initiated, including a Calcineurin Inhibitor (CNI), Mycophenolate Mofetil, and low-dose steroids (from 2016-2023), resulting in stable graft function with a creatinine level of 1.1mg/dl. In 2024, Mycophenolate Mofetil was shifted to Azathioprine due to repeated non-infectious diarrhoea. He presented with a flu-like illness followed by a 2-week history of slurred speech, ataxia, and nystagmus, with neurological evaluation showing cerebellar impairment, characterised by dysarthria and dysdiadochokinesia, dysmetria, and slow saccades. An impression of CNI-induced cerebellar dysfunction was made. Deep tendon reflexes were intact, and the plantar response was downgoing. However, he exhibited a striking inability in tandem walking.An MRI of the brain with contrast was done showing T2 hyperintensity involving the pons extending into superior cerebellar peduncles, and right cerebellar hemisphere. Findings that were suggestive of tacrolimus-induced encephalopathy with a differential diagnosis of infratentorial progressive multifocal leukoencephalopathy. CSF analysis revealed lymphocytosis.

 Consequently, CNI was discontinued, and tacrolimus levels were assessed, which were found to be within the therapeutic range. A multidisciplinary team (MDT) meeting was conducted, and Tacrolimus was changed to Everolimus (a kinase inhibitor). Further evaluation revealed positive HIV- 1 (RNA)PCR with a viral load of 910,000 IU/ml with CD4 count of 404 cells/mm3 and also detected CMV DNA An MRI of the brain with contrast was done, showing T2 hyperintensity involving the pons extending into superior cerebellar peduncles, and right cerebellar hemisphere. Findings that were suggestive of tacrolimus-induced encephalopathy with a differential diagnosis of infratentorial progressive multifocal leukoencephalopathy. CSF analysis revealed lymphocytosis. PCR for which CMVIR was started. He was managed as a case of Acute Cerebellar Ataxia with HIV infection on a background of immunosuppressive therapy, substance abuse, and homosexual orientation. He was started on antiretroviral therapy with NRTI (Abacavir), an integrase inhibitor (dolutegravir), NRTI (Lamivudine), and Valganciclovir. For comparative analysis MRI of the brain with contrast was done on 26 May 2025, showing features more in favour of infratentorial progressive leukoencephalopathy (PML). Additional workup included PCR for BK/JC Virus, which was initially negative but later turned positive on repeat testing due to high clinical suspicion. The patient is currently receiving palliative care.

Atypical neurological symptoms such as cerebral ataxia can be a symptom of HIV, particularly in immunocompromised people like recipients of renal transplants. Imaging and laboratory workup are still necessary to rule out opportunistic infections such as PML, cryptococcus, and toxoplasmosis, even with adequate CD4 levels. It is important to perform routine HIV, hepatitis B, and hepatitis C screening prior to starting immunosuppressive therapy. Even in unusual situations, neurological impairments can still be reversed with early detection and prompt antiretroviral therapy.