Neurocandidiasis results from disseminated infection of the central nervous system by the fungus Candida albicans, usually manifesting as cerebral micro-abscesses and meningitis.
CNS disease is thought to occur in up to 52% of patients with disseminated candidiasis, but predominates in immunocompromised individuals 1,2.
Risk factors include 1,2:
- prolonged high-dose corticosteroid use
- neutropaenia, especially in the setting of haematological malignancies
- graft-vs-host disease after allogeneic bone marrow transplantation
- neonates with recent neurosurgery
- patients with CNS shunts and other devices
Patients with neurocandidiasis have a varied presentation, but most commonly exhibit symptoms akin to an acute or chronic bacterial meningitis, however these symptoms may be subtle or absent in neonates or severely neutropaenic patients 1,2. Furthermore, in patients with multiple cerebral micro-abscesses, a diffuse encephalopathy may be the predominant clinical presentation, however this is also often subtle 1.
Neurocandidiasis most commonly results from disseminated haematogenous infection of Candida albicans, but can rarely also be due to other Candida spp. such as Candida parapsilosis, Candida tropicalis, and Candida glabrate 3. In addition to haematogenous spread to the CNS, Candida may also be introduced to the CNS during craniotomy or through the presence of a CNS shunt 3.
Once in the CNS, and due to their small size, Candida has a predilection for the microcirculation, classically resulting in multiple cerebral micro-abscesses and leptomeningitis 4. However, Candida can also uncommonly cause the development of mycotic aneurysms resulting in intracerebral haemorrhage or subarachnoid haemorrhage, thrombosis in small perforating arterioles resulting in ischaemic stroke, cerebral macro-abscesses, and cerebral vasculitis 1,2.
The disease can have a variety of radiographic features, but the main two findings are 1,2:
- multiple micro-abscesses
CT findings can often be subtle and non-specific 1. The most common reported feature is secondary communicating hydrocephalus reflective of leptomeningitis, however this is still an uncommon finding seen in only 20% of cases 1,2. Micro-abscesses are very rarely appreciated on CT 1.
Micro-abscesses are the hallmark radiographic feature of neurocandidiasis 1,2. They are less than 3mm in size, multiple, and most commonly located at the gray-white matter junction, basal ganglia, and/or cerebellum 1,5-9. These micro-abscesses have MR signal characteristics that are identical to other brain abscesses, those being classic ring-enhancing lesions with striking high signal intensity on DWI 1,5-9. Small haemorrhagic components are also commonly observed, which may demonstrate low signal intensity on T2-weighted images and may be better appreciated on GRE or SWI images 1,2,5.
In addition to secondary communicating hydrocephalus, MRI may reveal non-specific leptomeningeal enhancement on post-gadolinium images 1. However, this enhancement does not occur in any specific distribution making it therefore indistinguishable from bacterial leptomeningitis, and is also uncommonly reported 1.
As aforementioned, rarely neurocandidiasis can present with other clinico-radiological features:
- intracerebral haemorrhage or subarachnoid haemorrhage with or without identifiable mycotic aneurysms 1,2
- ischaemic stroke, especially in the territories of perforating arteries such as the basal ganglia 1,2
- cerebral macro-abscesses, usually located in the parieto-occipital region 1,2
- cerebral vasculitis 2
Treatment and prognosis
Neurocandidiasis is treated with intravenous antifungal agents such as liposomal amphotericin B and flucytosine 1. Neurosurgical opinion and intervention may also be sought if CNS shunt infection is suspected 1. Mortality of neurocandidiasis is reported to be up to 30% 9.
General imaging differential considerations include:
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- 2. Jain KK, Mittal SK, Kumar S, Gupta RK. Imaging features of central nervous system fungal infections. Neurology India. 55 (3): 241-50. Pubmed
- 3. Chiou CC, Wong TT, Lin HH, Hwang B, Tang RB, Wu KG, Lee BH. Fungal infection of ventriculoperitoneal shunts in children. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 19 (6): 1049-53. Pubmed
- 4. Gavito-Higuera J, Mullins CB, Ramos-Duran L, Olivas Chacon CI, Hakim N, Palacios E. Fungal Infections of the Central Nervous System: A Pictorial Review. Journal of clinical imaging science. 6: 24. doi:10.4103/2156-7514.184244 - Pubmed
- 5. Lai PH, Lin SM, Pan HB, Yang CF. Disseminated miliary cerebral candidiasis. AJNR. American journal of neuroradiology. 18 (7): 1303-6. Pubmed
- 6. Lin DJ, Sacks A, Shen J, Lee TC. Neurocandidiasis: a case report and consideration of the causes of restricted diffusion. Journal of radiology case reports. 7 (5): 1-5. doi:10.3941/jrcr.v7i5.1319 - Pubmed
- 7. Huang CC, Chen CY, Yang HB, Wang SM, Chang YC, Liu CC. Central nervous system candidiasis in very low-birth-weight premature neonates and infants: US characteristics and histopathologic and MR imaging correlates in five patients. Radiology. 209 (1): 49-56. doi:10.1148/radiology.209.1.9769811 - Pubmed
- 8. Pendlebury WW, Perl DP, Munoz DG. Multiple microabscesses in the central nervous system: a clinicopathologic study. Journal of neuropathology and experimental neurology. 48 (3): 290-300. Pubmed
- 9. Voice RA, Bradley SF, Sangeorzan JA, Kauffman CA. Chronic candidal meningitis: an uncommon manifestation of candidiasis. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 19 (1): 60-6. Pubmed
Infections of the central nervous system
- classification by aetiology
- eastern equine encephalitis
- enterovirus rhomboencephalitis
- flavivirus encephalitis
herpes virus family
- herpes simplex virus 1 (HSV-1) encephalitis
- herpes simplex virus 2 (HSV-2) encephalitis
- varicella zoster virus (VZV) encephalitis
- Epstein-Barr virus (EBV) encephalitis
- cytomegalovirus (CMV) encephalitis
- human herpesvirus 6 (HHV-6) encephalitis
- HIV CNS manifestations
- HTLV-1-associated myelopathy
- JC virus
- measles encephalitis
- Nipah virus (NiV) encephalitis
- rabies encephalitis
- CNS listeriosis (Listeria monocytogenes)
- CNS nocardiosis (Nocardia spp)
- CNS tuberculosis (Mycobacterium tuberculosis)
- Lyme disease (Borrelia burgdorferi)
- neurosyphilis (Treponema pallidum)
- Rocky Mountain spotted fever (Rickettsia rickettsii)
- cerebral amoebiasis
- cerebral malaria (Plasmodium falciparum)
- cerebral sparganosis (Spirometra mansonoides)
- neurocysticercosis (Taenia solium)
- neurohydatidosis (Echinococcus spp)
- neurotoxoplasmosis (Toxoplasma gondii)
- others or those with possible infectious aetiologies
- classification by location
- meninges and ventricular system
- brain parenchyma, brainstem, and spinal cord
- classification by aetiology