How does Cryptococcus cause cranial hypertension?

Mechanism of Cryptococcal Cranial Hypertension

Cryptococcus causes cranial hypertension primarily through reduced CSF outflow due to increased outflow resistance from high fungal burden in the CSF, not through prominent cerebral edema. 1, 2

Primary Pathophysiologic Mechanism

The elevated intracranial pressure in cryptococcal meningitis is directly linked to the high burden of yeast organisms in the CSF, which impairs normal CSF drainage pathways. 1 This mechanism operates through:

• Impaired CSF absorption: The massive fungal load physically obstructs arachnoid granulations and CSF outflow pathways, increasing outflow resistance rather than causing significant cerebral edema 2
• Prevalence: Approximately 50-75% of patients with cryptococcal meningitis develop elevated intracranial pressure (≥200 mm H₂O), making this an extremely common complication 3
• Severity correlation: One-half of HIV-infected patients have baseline pressures >25 cm CSF, and one-fourth have pressures >35 cm CSF 1

Secondary Mechanisms in Different Patient Populations

HIV-negative patients may develop elevated CSF pressure through additional inflammatory mechanisms:

• Robust inflammatory responses in the meninges leading to meningeal thickening 1
• Cryptococcomas (fungal mass lesions) causing mass effect 3
• Communicating or obstructive hydrocephalus from inflammatory debris 3
• Cerebral vasculitis with potential for herniation risk 1

HIV-positive patients typically present with:

• Minimal inflammatory response despite high fungal burden 1
• Cerebral atrophy without classic hydrocephalus on imaging 1
• Normal or unremarkable radiographic findings in most cases 1

Clinical Consequences of the Mechanism

The elevated pressure directly causes:

• Early mortality: Patients who died within the first 2 weeks of therapy had baseline pressures ≥25 cm CSF 1
• Neurologic morbidity: Papilledema (29% in high-pressure group), impaired mentation (18%), visual loss, hearing loss, and cranial nerve palsies 1, 3, 4
• Immediate symptoms: Severe headaches that often resolve immediately after CSF drainage 1

Critical Clinical Pitfall

Medical therapies targeting cerebral edema are ineffective and potentially harmful because the mechanism is obstructive rather than vasogenic:

• Corticosteroids showed no benefit and potentially increased mortality in a study of 41 HIV-infected patients 1
• Acetazolamide caused severe metabolic acidosis and a randomized trial in Thailand was stopped prematurely 1
• Mannitol has not been shown effective for cryptococcal-related intracranial hypertension 3, 5

Management Implications Based on Mechanism

Since the mechanism is mechanical obstruction from fungal burden, treatment must focus on:

• Physical CSF drainage to reduce pressure by 50% or to <20 cm CSF 1, 3
• Fungicidal antifungal therapy to reduce the yeast burden causing obstruction 1
• Serial lumbar punctures until CSF sterilization reduces the obstructive load 1, 3
• Temporary or permanent shunting when conservative drainage fails to overcome the outflow resistance 1, 3

The understanding that this is an obstructive rather than inflammatory mechanism explains why aggressive CSF drainage is the cornerstone of management and why anti-inflammatory medications fail. 1, 2