Differential Diagnosis of Chorea—HIV Infection Delays Diagnosis of Huntington’s Disease by Years

Abstract

Background: There is a broad range of potential differential diagnoses for chorea. Besides rare, inherited neurodegenerative diseases such as Huntington’s disease (HD) chorea can accompany basal ganglia disorders due to vasculitis or infections, e.g., with the human immunodeficiency virus (HIV). The clinical picture is complicated by the rare occurrence of HIV infection and HD. Methods: First, we present a case suffering simultaneously from HIV and HD (HIV/HD) focusing on clinical manifestation and disease onset. We investigated cross-sectional data regarding molecular genetic, motoric, cognitive, functional, and psychiatric disease manifestation of HIV/HD in comparison to motor-manifest HD patients without HIV infection (nonHIV/HD) in the largest cohort of HD patients worldwide using the registry study ENROLL-HD. Data were analyzed using ANCOVA analyses controlling for covariates of age and CAG repeat length between groups in IBM SPSS Statistics V.25. Results: The HD diagnosis in our case report was delayed by approximately nine years due to the false assumption that the HIV infection might have been the cause of chorea. Out of n = 21,116 participants in ENROLL-HD, we identified n = 10,125 motor-manifest HD patients. n = 23 male participants were classified as suffering from HIV infection as a comorbidity, compared to n = 4898 male non-HIV/HD patients. Except for age, with HIV/HD being significantly younger (p < 0.050), we observed no group differences regarding sociodemographic, genetic, educational, motoric, functional, and cognitive parameters. Male HIV/HD patients reported about a 5.3-year-earlier onset of HD symptoms noticed by themselves compared to non-HIV/HD (p < 0.050). Moreover, patients in the HIV/HD group had a longer diagnostic delay of 1.8 years between onset of symptoms and HD diagnosis and a longer time regarding assessment of first symptoms by the rater and judgement of the patient (all p < 0.050). Unexpectedly, HIV/HD patients showed less irritability in the Hospital Anxiety and Depression Scale (all p < 0.05). Conclusions: The HD diagnosis in HIV-infected male patients is secured with a diagnostic delay between first symptoms noticed by the patient and final diagnosis. Treating physicians therefore should be sensitized to think of potential alternative diagnoses in HIV-infected patients also afflicted by movement disorders, especially if there is evidence of subcortical atrophy and a history of hyperkinesia, even without a clear HD-family history. Those patients should be transferred for early genetic testing to avoid further unnecessary diagnostics and improve sociomedical care.

Another Perspective on Huntington’s Disease: Disease Burden in Family Members and Pre-Manifest HD When Compared to Genotype-Negative Participants from ENROLL-HD

“…All sites are required to obtain and maintain local ethical approval. We investigated the periodic dataset five (PDS5), as described previously [ 33 , 34 ] Ethics approval was obtained by the local ethics committee of Ruhr-University Bochum (No. 4941-14).…”

Diagnostic Uncertainties: Chorea

“…The authors recommend a careful family history and strong consideration of HD testing to be included in any case of suspected HIV-associated chorea. 53 Despite its reputation as the great mimicker, neurosyphilis appears to be a rare cause of chorea, at least in the modern era, and is usually concomitant with HIV infection. One case report of a 70-year-old HIV-negative man who presented with 10 years of chorea and a positive CSF Venereal Disease Research Laboratory (VDRL) and Fluorescent treponemal antibody absorption (FTA-ABS) test was reported in 2009.…”

“…55 Due to this nonspecific presentation, there is clinical overlap between HIV-associated chorea and early HD, which can delay diagnosis of the latter. 53 It is also suggested that the concomitant HAD and HD will result in earlier onset of symptoms and a more severe phenotype. One study using data from the ENROLL-HD database found that of 10,000 HD manifest patients, the 25 patients who were also HIV positive had a longer lag time, on average about 2 years, between onset of symptoms and HD diagnosis when compared with their HIV-negative counterparts.…”

Role of Autophagy in HIV-1 and Drug Abuse-Mediated Neuroinflammaging

“…The authors further demonstrated that the p75ntr supports Purkinje neuron survival in the presence of trophic factors but promotes autophagy and death of Purkinje neurons in the absence of trophic stimuli [ 173 ]. Emerging studies suggest that HIV +ve /HD patients exhibit an earlier onset of HD symptoms than HIV −ve /HD patients [ 174 , 175 , 176 ]. Studies also demonstrated that in these patients, dysregulation of neuronal autophagy was associated with HIV-1 dementia and encephalitis [ 167 , 168 ].…”