Cryptococcal Meningitis in a Patient with Hepatitis C Cirrhosis Presenting with Acute Demyelinating Polyneuropathy of the Guillian-Barré Type

Al Ani M.A., Mubarak A.A., Al Azawi A. and Al Qahtani A.
Department of Medicine, Hamad Medical Corporation, Doha, Qatar

Abstract:

Key words: Cryptococcal Meningitis, Liver cirrhosis

Introduction:

Cryptococcal meningitis is caused by Cryptococcus neoformans, a ubiquitous encapsulated yeast of which two varieties are significant in man, C. neoformans var. neoformans and C. neoformans var. gatti^[1] . The organism has been found in dried pigeon droppings, contaminated soil and leaf and bark samples from various gum trees growing in tropical and subtropical regions. The organism can also be detected in air samples when the trees are flowering^[1] (Ellis and Pfeiffer 1990). Meningitis is the most common presentation of cryptococcosis. Patients with liver cirrhosis are at increased risk of fungal infection because of decreased opsonin function, impaired complement and leukocyte dysfunction^[2].

Case Report :

A fifty-four year old Egyptian male presented with one-week history of progressive weakness of the lower limbs. He was unable to climb the stairs or to stand up from sitting position. There was no history of fever, headache, nausea, vomiting or change in bowel habits. He was a known case of hepatitis C cirrhosis complicated by gastric and oesophageal varices for the last three years.

Laboratory Investigations:

Blood count revealed a white cell count of 3.09 cells/mm³, Hb 9.25 g/dl, platelets 39.8 /mm³, International normalised ratio 1.4. CD3 and CD4, alpha-fetoprotein, thyroid function tests, urea and electrolytes, liver function tests, CT of brain were all normal, and he was HIV negative. An MRI of the thoraco-lumbar spine did not show any evidence of cord compression. Nerve conduction studies showed a slight delay in motor latency of the left median nerve, slight reduction of conduction of the left peronius profundus nerve, delayed f-wave latency of the left peronius profundus with conduction block; findings consistent with early demyelinating neuropathy. Sensory conduction was normal. Lumbar puncture examination was suggestive of meningitis, WBC 2200/mm³. lymphocytes 15%, polymorphs 85%. Grams stain, Bacterial latex test, and stain for AFB’s were all negative. Culture produced a growth of Cryptococcus neoformans. The patient was started on amphotericin B but developed renal failure after the second dose and treatment was changed to fluconazole 400 mg orally once daily. After four weeks, the lumbar puncture was repeated. A cell count was not done because of contamination with extraneous blood. After centrifugation, cytology showed numerous lymphocytes. Culture produced no fungal growth. Treatment continued for ten weeks with remarkable increasing strength of the patient who is now doing well 18 months after discharge from the hospital.

Discussion:

Cryptococcosis is a life-threatening systemic fungal infection caused by monomorphic yeast Cryptococcus neoformans^[3]. Despite the high prevalence of the organism in the environment, human cryptococcal infection is rare except in patients with disorders of cell-mediated immunity such as AIDS, immuno-suppression and lympho-reticular malignancies.

Our patient was known to have hepatitis C cirrhosis and portal hypertension and he presented with progressive proximal lower limb weakness with areflexia and neurophysiological findings consistent with the diagnosis of Guillian-Barré syndrome, a presentation reported before^[4]. Patients with liver cirrhosis due to elevated levels of chemotactic inhibitors and reduced complement level are at higher risk of bacterial and fungal infections. ^[5]. One study found liver cirrhosis to be the underlying cause of cryptococcal illness in 6.3%. (third commonest cause)^[2]. Rare case reports of cryptococcal peritonitis ^[2] , arthritis and myositis[6] have been described in patients with hepatic dysfunction.

Meningitis is the most common presentation of cryptococcal infection, and CNS disease may be accompanied by infection in extra-cranial sites, particularly the lungs which may be the primary site of infection^[1,7]. In one of the most comprehensive studies of the clinical features of cryptococcosis, the CNS was involved in 76% of 171 patients with similar rates for immunocompetent and immunosuppressed with or without AIDS^[8].

A myriad of neurological symptoms has been reported. Headache and fever being the most common followed by neck stiffness (75%), nausea and vomiting (50%)^{[ 9]}. The signs of meningeal irritation may take weeks to develop ^[10]. The early diagnosis and treatment in our patient might explain the absence of these signs.

Diagnosis is established by demonstrating Cryptococcus neoformans during the active disease state. This may be done by direct microscopic examination of CSF using an Indian ink preparation, by isolation in culture or by detection of cryptococcal antigen. Culture yields the organism in 87 to 100%^[10]. CSF culture was positive in our patient and treatment with amphotericin B was initiated but the renal function deteriorated after the second dose and treatment was changed to fluconazole. The CSF was sterile after four weeks of treatment but fluconazole was continued for ten weeks.

Recent studies that have identified optimal treatment strategies for cryptococcal infections have been of patients with AIDS. These studies suggest initial treatment with amphotericin B with or without flucytocine which allows more rapid sterilization of CSF than fluconazole[6], Fluconaxole 400 mg daily for ten weeks has been used as an alternative to amphotericin B in treating cryptococcal meningitis in AIDS^[11]

In a study of meningeal and extra-meningeal cryptococcosis in HIV-negative patients treated with amphotericin B (43 patients) or fluconazole (40 patients), a cure rate of 77% was achieved in both groups of patients and fluconazole appears as effective as amphotericine B^[12].

Acknowledgements:

References: