Parkinsonism and prolonged cognitive decline as a manifestation of cryptococcal meningitis in a renal transplant patient

Abstract

We report a case of a 67-year-old male recipient of a second renal allograft, presenting with a 9-month history of progressive cognitive and physical decline with features of Parkinsonism. He was HIV-negative. Serum and cerebrospinal fluid (CSF) cryptococcal antigen was positive though CSF culture was sterile. He had progressive deterioration despite induction and consolidation antifungal treatment. Postmortem brain examination confirmed a large burden of yeast forms in the substantia nigra with widespread chronic meningitis. The significant delay in presentation and diagnosis owing to the atypical, subacute neurocognitive features serves as a timely reminder of the variety of neurological presentations that may be associated with cryptococcal infection in solid organ transplant recipients.

Infections of Cryptococcus species induce degeneration of dopaminergic neurons and accumulation of α-Synuclein in Caenorhabditis elegans

“…Moreover, we found that infections of C. neoformans and C. gattii induced the degeneration of DA neurons and accelerated aging similarly to the 6-OHDA treatment ( Figure 1C ). These observations have led to the suggestion that invasive cryptococcal infections can induce cellular cytotoxicity and CNS tissue compression leading to the death of DA neurons as seen our present study and in patients with cryptococcal meningoencephalitis associated with prominent features of Parkinsonism ( Wszolek et al., 1988 ; Pedroso and Barsottini, 2012 ; Nelles et al., 2022 ). Therefore, C. elegans can be used as a model to investigate the pathogenesis of cryptococcal infection that induces DA neuronal degeneration related to Parkinsonian symptoms.…”

“…Patients with cryptococcal-induced Parkinsonism are often presented with prominent clinical characteristics including bradykinesia, tremor, rigidity, and postural instability. Postmortem brain examination has confirmed the fungal burden located at the substantia nigra and in basal ganglia suggesting the root-cause of Parkinsonism (Wszolek et al, 1988;Pedroso and Barsottini, 2012;Nelles et al, 2022). Degeneration of dopaminergic (DA) neurons of the substantia nigra and a-synucleinopathies are the common denominators of Parkinsonism during aging (Dickson, 2012).…”

Cryptococcal Meningitis in Kidney Transplant Recipients: A Two-Decade Cohort Study in France

“…For CM, studies dedicated to non-human immunodeficiency virus (HIV) patients have further highlighted some of the specific aspects of cryptococcosis in this population, including risk factors associated with neurological involvement [7], the role of plasma and/or cerebrospinal fluid (CSF) cryptococcal antigen (Ag) for prognostic evaluation [8], and the neurological complications of the disease [9]. However, CM outcomes-as well as its clinical features, radiological characteristics, and laboratory findings-have not been analyzed in a large cohort in this particular population [10][11][12].…”