Cryptococcal meningitis

Cryptococcosis is a fungal infection caused by Cryptococcus spp. that enters the body via inhalation, which mainly invades the lungs and central nervous system.

Two types of fungus can cause cryptococcal meningitis (CM). They are called Cryptococcus neoformans (C. neoformans) and Cryptococcus gattii (C.gattii). This disease is rare in healthy people. CM is more common in people who have compromised immune systems, such as people who have AIDS.

Cryptococcal meningitis may have long-term morbidity and requires a permanent cerebrospinal fluid shunt.

see Cryptococcus neoformans ventriculoperitoneal shunt infection.

see Cryptococcal choroid plexitis.

Cryptococcal meningitis are usually subacute or chronic in nature. HIV-infected patients may have minimal or nonspecific symptoms. Common symptoms are as follows:

Headache

Confusion

Lethargy

Obtundation

Coma

Normal or mildly elevated temperature

Nausea and vomiting (with increased intracranial pressure)

Fever and stiff neck (with an aggressive inflammatory response; less common)

Blurred vision, photophobia, and diplopia

Hearing defects, seizures, ataxia, aphasia, and choreoathetoid movements

After lung and CNS infection, the next most commonly involved organs in disseminated cryptococcosis include the skin, the prostate, and the medullary cavity of bones. Cutaneous manifestations (10-15% of cases) are as follows:

Papules, pustules, nodules, ulcers, or draining sinuses

Umbilicated papules in patients with AIDS

Cellulitis with necrotizing vasculitis in organ transplant recipients

Other less common forms of cryptococcosis include the following:

Optic neuritis or endophthalmitis

Myocarditis

Chorioretinitis

Hepatitis

Peritonitis

Renal abscess

Myositis

Adrenal involvement

The workup in patients with suspected cryptococcosis includes the following:

Cutaneous lesions: Biopsy with fungal stains and cultures

Blood: Fungal culture, cryptococcal serology, and cryptococcal antigen testing

Cerebrospinal fluid: India ink smear, fungal culture, and cryptococcal antigen testing

Urine and sputum cultures, even if renal or pulmonary disease is not clinically evident

In AIDS patients with cryptococcal pneumonia, culture of bronchoalveolar lavage washings

With possible CNS cryptococcosis, especially in patients who present with focal neurologic deficits or a history compatible with slowly progressive meningitis, consider obtaining a computed tomography or magnetic resonance imaging scan of the brain prior to performing a lumbar puncture. If a mass lesion is identified, do not perform a lumbar puncture to obtain spinal fluid; rather, consult a neurosurgeon for an alternative procedure.

With pulmonary cryptococcosis, radiographic findings in patients who are asymptomatic and immunocompetent may include the following:

Patchy pneumonitis

Granulomas ranging from 2-7 cm

Miliary disease similar to that in tuberculosis.

Current management involves a sequential, longitudinal regimen of antifungals; despite a significant improvement in survival compared to uniform mortality without treatment, this drug paradigm has not led to a consistent cure. NeurapheresisTM therapy, extracorporeal filtration of yeasts from cerebrospinal fluid (CSF) in infected hosts, is presented here as a novel, one-time therapy for CM. In vitro filtration of CSF through this platform yielded a five-log reduction in concentration of the yeast and a one-log reduction in its polysaccharide antigen over 24 hours. Additionally, an analogous closed-loop system achieved 97% clearance of yeasts from the subarachnoid space in a rabbit model over 4-6 hours. This is the first publication demonstrating the direct ability to rapidly clear, both in vitro and in vivo, the otherwise slowly-removed fungal pathogen that directly contributes to the morbidity and mortality seen in CM ¹⁾.

Treatment of cryptococcal meningitis consists of three phases: induction, consolidation, and maintenance. Effective induction therapy requires potent fungicidal drugs (amphotericin B and flucytosine), which are often unavailable in low-resource, high-endemicity settings. As a consequence, mortality is unacceptably high. Wider access to effective treatment is urgently required to improve outcomes. For human immunodeficiency virus-infected patients, judicious management of asymptomatic cryptococcal antigenemia and appropriately timed introduction of antiretroviral therapy are important ²⁾.

A study aimed to evaluate the risk factors and create a predictive model for permanent shunt treatment in cryptococcal meningitis patients. This was a retrospective analytical study conducted at Khon Kaen University. The study period was from January 2005 to December 2015.

They enrolled all adult patients diagnosed with cryptococcal meningitis. Risk factors predictive for permanent shunting treatment were analyzed by multivariate logistic regression analysis. There were 341 patients diagnosed with cryptococcal meningitis. Of those, 64 patients (18.7%) were treated with permanent shunts. There were three independent factors associated with permanent shunt treatment. The presence of hydrocephalus had the highest adjusted OR at 56.77. The resulting predictive model for permanent shunt treatment (y) is (-3.85) + (4.04 × hydrocephalus) + (2.13 × initial CSF opening pressure (OP) > 25 cm H2O) + (1.87 × non-HIV). In conclusion, non-HIV status, initial CSF OP greater than or equal to 25 cm H2O, and the presence of hydrocephalus are indicators of the future necessity for permanent shunt therapy ³⁾.

In Japan, most cases of cryptococcosis are caused by Cryptococcus neoformans(C. neoformans). Until now, only three cases which the infectious agent was Cryptococcus neoformans var. gattii(C. gattii)have been reported. As compared with cryptococcosis caused by C. neoformans, which is often observed in immunocompromised hosts, cryptococcosis caused by C. gattii occurs predominantly in immunocompetent hosts and is resistant to antifungal drugs. Here, we report a case of refractory cerebral cryptococcoma that was successfully treated by surgical resection of the lesions. A 33-year-old man with no medical history complained of headache, hearing disturbance, and irritability. Pulmonary CT showed a nodular lesion in the left lung. Cerebrospinal fluid examination with Indian ink indicated cryptococcal meningitis, and PCR confirmed infection with C. gattii. C. gattii is usually seen in the tropics and subtropics. Since this patient imported trees and soils from abroad to feed stag beetles, parasite or fungal infection was, as such, suspected. Although he received 2 years of intravenous and intraventricular antifungal treatment, brain cryptococcomas were formed and gradually increased. Because of the refractory clinical course, the patient underwent surgical resection of the cerebral lesions. With continuation of antifungal drugs for 6 months after the surgeries, Cryptococcus could not be cultured from cerebrospinal fluid, and no lesions were seen on MR images. If cerebral cryptococcosis responds poorly to antifungal agents, surgical treatment of the cerebral lesion should be considered. ⁴⁾.