CNS aspergillosis

CNS aspergillosis results from angioinvasive infection of the central nervous system by the fungus Aspergillus spp. Along with CNS cryptococcosis, it is one of the most common fungal opportunistic infections of the central nervous system.

The disease predominates in immunocompromised individuals, such as those with:

  • AIDS
  • prolonged high-dose corticosteroid use
  • neutropaenia
  • graft-vs-host disease after allogeneic bone marrow transplantation 1-4

Patients with CNS aspergillosis have a very varied, and often subtle, presentation, making initial diagnosis difficult 1,2. However, the most common presenting features, with or without fever, are 1,2:

  • altered mental status
  • headache
  • focal neurological signs (e.g. hemiparesis, dysarthria)
  • lethargy
  • seizures

There are two mechanisms of spread of Aspergillus spp to the CNS 1-3. Firstly, as per the pathogenesis of angioinvasive aspergillosis, spores of a variety of Aspergillus spp, most commonly Aspergillus fumigatus, are inhaled and proliferate in the alveoli, where the hyphae invade pulmonary arteries and gain access to the systemic circulation in 25-50% of cases 4. Once in the systemic circulation, spores can haematogenously spread to the CNS 1-4. Additionally, aspergillosis can also directly spread to the CNS via the paranasal sinuses, where it may manifest as invasive fungal rhinosinusitis 1-3.

Once in the CNS, the Aspergillus hyphae invade the walls of both small and large blood vessels 1,2. This either results in initial thrombosis leading to infarction, often followed by haemorrhage (in 25%), or development of mycotic aneurysms which can haemorrhage 1-3. This haemorrhage may lead to further parenchymal seeding of Aspergillus, resulting in infectious cerebritis and eventual brain abscess formation, often multiple in nature 3.

The disease can have a variety of radiographic presentations, but the main three findings are:

  • brain abscess, often multiple, in a random distribution 1-3
  • cerebral infarction(s) with or without associated haematoma(s) in a random distribution, although more likely to affect perforating artery territories 1-3
  • invasive paranasal rhinosinusitis, either acute or chronic, with secondary intracranial dural enhancement consistent with intracerebral extension from the sinuses 1-3

CT findings can be often non-specific but in keeping with at least one of the main three aforementioned findings that are characteristic of CNS aspergillosis 1-2. Detecting multiple such lesions in an immunosuppressed patient should prompt further investigation with MRI.

Abscesses (and prior regions of cerebritis) are often multiple, present in a random distribution, and appear radiologically identical to other brain abscesses as classic ring-enhancing lesions with striking high signal intensity on DWI 1-3,5. However, Aspergillus abscesses may also have peripheral low signal intensity on T2-weighted images 2. This is better appreciated on GRE or SWI images, and is likely due to surrounding haemorrhage around the abscess 2.

In cases where CNS aspergillosis is secondary to paranasal sinus disease, associated invasive rhinosinusitis (either acute or chronic), osteomyelitis, local dural enhancement and subdural empyema may also be present 3.  

Again, infarcts are often multiple, present in a random distribution, and are radiologically identical to other ischaemic strokes 1-3,5, especially those of perforating artery territories 3. Haemorrhage is present in up to 25%, and mycotic aneurysms may or may not be identified 1. Infarction and associated haemorrhage have a variety of appearances on MRI depending on their age (see ischaemic stroke and ageing blood on MRI).

Rarely, CNS aspergillosis can also present with a granulomatous tumour-like mass lesion 6,7. These, as described in case reports, are often hypo-to-isointense on T1-weighted images, hypointense on T2-weighted images, and demonstrate contrast enhancement on post-gadolinium T1-weighted images, but there is thought to be considerable variation 7,8.

CNS aspergillosis is treated with intravenous voriconazole 1-3,9,10, possibly in combination with caspofungin or liposomal amphotericin B 9. Neurosurgical opinion and intervention may also be sought 9. In immunocompromised hosts, which encompasses nearly all cases, it has a mortality approaching 100% if left untreated 1,2,10.

General imaging differential considerations include:

Infections of the central nervous system
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Article information

rID: 53818
Synonyms or Alternate Spellings:
  • Central nervous system aspergillosis
  • Angioinvasive CNS aspergillosis
  • Angioinvasive central nervous system aspergillosis

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Cases and figures

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    Case 1: with cerebral abscess
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    Case 2: with cerebral abscesses
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    Case 3: with extension from invasive sinusitis
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    Case 4: possible, with cerebral abscesses
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