Bruce J. Brew
Immunology/HIV/Infectious Diseases Clinical Services Unit and Department of Neurology, St Vincent’s Hospital, Sydney NSW
Zachary J. Webb-Harvey
Immunology/HIV/Infectious Diseases Clinical Services Unit, St Vincent’s Hospital, Sydney NSW
When evaluating neurological presentations in context of HIV (Human immunodeficiency virus) the differential diagnosis is determined by the stage of HIV infection, previous treatment history, medication compliance, and objective evidence of involvement of the central and/or peripheral nervous system. This case study illustrates several diagnostic and management issues in approaching neurological symptoms in people living with HIV (PLWH). Details of the underlying conditions will be elucidated in the following section ‘Neurological disorders in HIV infection’.
| Case study – Neurological symptoms in an immunodeficient PLWH |
| Sebastian is a 58-year-old married man with HIV-1 infection. He has partially adhered to combined antiretroviral therapy (cART) and has progressed through multiple cART regimens, including nucleoside reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI) and protease inhibitors (PI) due to intolerable adverse drug reaction or virological failure. Sebastian is currently taking an antiretroviral drug regimen of tenofovir disoproxil fumarate, emtricitabine, and darunavir boosted with ritonavir. His most recent CD4 cell count is 70 cells/μL and HIV viral load is 79,432 (4.9 log10) HIV RNA copies/mL. Sebastian has been poorly adherent to trimethoprim/sulfamethoxazole prophylaxis, evidenced by infrequently filled prescriptions. He is up to date with regular vaccinations. Sebastian has no known tuberculosis risk factors in terms of contacts or travel to endemic areas. He thinks he had syphilis treatment many years ago but cannot remember the details. He has a family history of myocardial infarction. He continues to smoke though is trying to quit. He has used methamphetamine in the past but not for several years.
Sebastian is referred to a HIV physician after his husband reported that he has had difficulty walking and recently ‘isn’t quite himself’. On review, he reports subjective cognitive slowness and gait disturbance. He and his husband confirm poor adherence to cART due to significant nausea with his current regimen. A directed history reveals he has experienced intermittent headaches and possibly fevers, although no rigors. He drinks a modest amount of alcohol and does not take illicit drugs or non-prescribed medications. Examination reveals a well appearing, overweight, normotensive, afebrile man with reduced pinprick and light touch sensation to the ankles bilaterally with preservation of bilateral ankle jerks. Heel-toe gait is impaired, with a tendency to fall to the left. The serum Toxoplasma gondii immunoglobin G antibody assay was negative and syphilis serology was non-reactive when last performed 2 years ago. Biochemical tests reveal normal serum electrolytes and renal function. Serum B12, folate and thyroid-stimulating-hormone levels are normal. HBA1c is not elevated at 5.5%. Hepatitis B surface antigen and hepatitis C serology is negative. Treponemal syphilis serology is non-reactive, with positive non-treponemal serology in keeping with previous infection. CMV serology demonstrates a negative IgM, a positive IgG, and the CMV viral load is undetectable. MRI brain scan with spectroscopy (MRS) with gadolinium demonstrates diffuse T2 hyperintensies in periventricular and deep white matter with increased choline, myo-inositol and decreased n-acetyl aspartate (Figure 1) and no evidence of a mass lesion. Lumbar puncture (LP) reveals an opening pressure of 14 cm of water and the cerebrospinal fluid (CSF) appears clear and colourless. CSF biochemistry reveals a normal glucose concentration and a raised protein concentration of 0.57 g/L (normal range 0.15-0.45 g/L). Microscopy of CSF reveals a mononuclear cell pleocytosis of 10/mm3, and no organisms are seen on Gram stain or India ink stain. Tests for CSF and serum cryptococcal antigen reveal titres of less than 1:4. Toxoplasma, HSV and VZV PCR testing is negative. CSF mycobacterial culture is pending. The CSF HIV viral load is 11,000 (4.04 log10) HIV RNA copies/mL and the CSF beta 2-microglobulin concentration is 4 mg/L (0.2 – 1.5) and the neopterin level was 27 nmol/L (0 – 13). Formal neuropsychometric testing reveals deficits in attention and psychomotor processing speed. Given the absence of an alternative cause for the neurological manifestations and the consistent clinical and laboratory findings, the physician makes a diagnosis of concurrent HIV associated neurocognitive disorder (HAND) and HIV sensory neuropathy. Serum and CSF genotypic HIV resistance assays demonstrate no evidence of resistance of NRTIs or integrase inhibitors. Following the availability of these results the HIV physician switches Sebastian’s cART regimen to dolutegravir and tenofovir alafenamide/emtricitabine to improve tolerability, reduce pill burden thereby improving compliance and improving CNS penetration. |
| Table 1: Approach to the diagnosis of persistent headache, seizures, altered level of consciousness or focal neurological symptoms or signs in the immunodeficient patient with HIV infection |
| Initial assessment
History
Examination
Investigations
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| PICTURE OF MRS |
| Source: Bruce Brew, Immunology/HIV/Infectious Diseases Clinical Services Unit and Department of Neurology, St Vincent’s Hospital, Sydney NSW. Used with permission. |