Introduction

Background and objectives: the incidence of crytococcal meningitis (cm), formerly a relatively rare disease, has markedly increased in recent years due to the frequent occurrence of the opportunistic infection in human immunodeficiency virus (hiv)-positive patients₁ mainly in places where protease inhibitor, nucleoside reverse transcriptase, and non-nucleoside reverse transcriptase drugs remains unavailable. The fungus is acquired by inhalation and causes the initial lesion in the lungs; the pulmonary stage of infection is usually a symptomatic. The fungus disseminates in debilitated patients, usually involving the meninges. In hiv-negative patient's incidence of cm is related to immunosuppressive drugs used to prevent allograft rejection in organ transplanted recipients, and particularly steroids therapy seems to be associated with an increased risk factor for cm₂

Neuropsychiatry manifestations (npm) may be conditions that are directly attributed to hiv infection but sometimes these conditions existed before a person becomes hiv-positive and both contribute to increase level of unemployment, poverty, homeless and unhappiness. Patients presenting these conditions (npm-hiv) are more prompt to develop complications because most of them have limited access to health care, hiv primary care, new antiretroviral medications and poor compliance therefore they will have shortened hiv-related survival, severely impaired quality of life and worst prognosis compared with hiv patients without npm₁. In places where traditional believes and stigmas are strong enough to modify the environment of these patients the prognosis is even worst. We recognize that despite all the scientific progress observed in the last century, the npm, epilepsies, and cognitive disorders are still surrounded by a mysterious mist for the majority of the population, mainly in developing countries,₃,₄,₅,₆ we also agree that it is abominable see at the beginning of the third millennium; npm and epilepsy are still being considered as symptom of devilish possession by some alternative therapists, adherent to distinct creeds in many societies around the world₇

Based on our previous knowledge of this problem we selected a number of record from patients diagnosed as cm and hiv/aids with the aim to identify their npm and to determine any possible correlation between npm, complications, and clinical prognosis.

Material And Method

A total of 142 patients with cm presenting npm, admitted in medical wards of Umtata general hospital between December 09, 2003 and December 09, 2004 were selected retrospectively. The detailed clinical history of the patients regarding age, sex, clinical diagnosis, and drug therapy were recorded.

All patients were diagnosed as hiv/aids by Elisa test for HIV and all of them were in a late stage of hiv/aids being their cd4 count ranged between 97 and 2 cell/mm³. As a routine procedure, the purpose of each investigation or medical procedure was explained to each patient before consent was requested.

Most patients were treated with 400mg to 800mg of fluconazol, mannitol and acetazolamide; and nobody was on antiretroviral treatment; when was necessary lp to remove out from 15 to 30 ml of cerebrospinal fluid (CSF) on daily basis or alternating day was performed. From all patients, samples of CSF were sent to the laboratory for cytochemical tests, cryptococcal capsular polysaccharide antigen, gram's stain, fungal culture, and India ink smear.

Patients under suspicion of hiv-1 encephalitis, hiv-1 associated dementia, tuberculous meningitis, aseptic meningitis, partially treated meningitis, syphilis, or neurocysticercosis were excluded. Other exclusion criteria were: pregnancy, previous history of npm, cognitive problems, mood disturbances, history of panic or obsessive-compulsive disorder with or without personality disorders. Patients reported with previous or current history of stroke, alcoholism, electrolyte disturbances, were not selected for this study. Personal identification details written on their outpatient cards were omitted to ensure anonymity. To increase the confidentially of the selected patients the first page from in-patient documents regarding personal information was omitted during data collection. Correlation between symptoms of delirium (D), mania (M), depression (De), anxiety (A), psychosis (P), dementia (Dem), and hydrocephalus (H), stupor (S), coma (C), bilateral blindness (BB), abducens palsy (AP), and prognosis were done.

Clinical criteria used for identification of D: irritability, disorganized speech, inability to maintain a coherent stream of thought or action, acute changes in perception, impairment of attention or arousal, acute or sub-acute onset (unlike dementia) and be associated with disruptions of the sleep-wake cycles (i.e. diurnal fluctuations) and evidence of a general medical condition causing the condition. Illusions may be present. Clinical criteria used for identification of M: excessively elevated and/or irritable mood or at least 1 week of profound mood disturbance characterized by elation, irritability, or expansiveness, grandiosity, diminished need for sleep, excessive talking or pressured speech, racing thoughts or flight of ideas, clear evidence of distractibility, increased level of goal-focused activity at home, at work, or sexually, excessive pleasurable activities, often with painful consequences. Clinical criteria used for identification of De: for the same 2 weeks, if the person experiences 5 or more of the following symptoms, with at least 1 of them being either a depressed mood or characterized by a loss of pleasure or interest: depressed mood, markedly diminished pleasure or interest in nearly all activities, significant weight loss or gain or significant loss or increase in appetite, hypersomnia or insomnia, psychomotor retardation or agitation, loss of energy or fatigue, decreased concentration ability or marked indecisiveness, feeling of worthlessness or guilty, poor concentration, preoccupation with death or suicide. The symptoms caused significant impairment and distress. Clinical criteria used for identification of A: feeling of apprehension caused by anticipation of danger, expressions of tense, panicky, terrified, jittery, nervous, apprehensive, palpitations, tremors, twitching, hot and cold flashes, sweating, dry mouth, chest tightness, hypervigilance, and fears of losing control or of going crazy. Clinical criteria used for identification of P: inability to distinguish reality from fantasy; impaired reality testing, with the creation of the new reality, delusions, hallucinations, and confusion. Clinical criteria used for identification of Dem: acquired organic and global deterioration of intellectual functioning without clouding the consciousness, (diagnosis of exclusion), impairment of abstract thinking and judgment, not readily reversible abnormal perceptions, attention, and memory that are more or less untreatable, and prominent behavioural or language disturbance and personality changes. Clinical criteria used for identification of H: dilation of the ventricular system on ct scan of the brain. Clinical criteria used for identification of S: decreased level of consciousness responding only to pain and/or nociceptive stimulation. Clinical criteria used for identification of C: decreased level of consciousness no responding to any stimulation. Clinical criteria used for identification of BB: bilateral lost of vision. Clinical criteria used for identification of AP: paralysis or paresis of the lateral rectus and adduction of the eye.

Results

In 2 patients without manifestation of sarcoidosis hiv test was negative and cm was confirmed by the identification of numerous encapsulated yeasts and positive cryptococcal antigen in CSF. The commonest npm on this series was D (37 females and 30 males, 47%) and M episodes (26 females and 21 males, 33%) followed by De (18 females and 10 males, 19%) and A (15 females and 9 males, 16%) while P manifestations were less common (6%) and Dem was not identified. (Table I). One patient presented a bipolar disorder.

Figure 1

Figure 2

Thirty-two patients presenting M developed conscious level disorder (S/C) and 29 presenting D had similar complications. H was confirmed by ct scan of the brain in 18 patients with M and/or d (see Table II). Most of patients with CM and NPM improved after serial LP was done however those presenting with D or/and M and S/C for more than 48 hours (n=62) or an associated H (n=37) had fatal prognosis (p<0.001) while others presenting AP secondary to intracranial hypertension or bb had better prognosis (see Table III) although their npm does not improved to much after serial LP. Hearing loss was not clinically identified on this series.

Figure 3

Comments

Conclusion

The positive rates of cryptococci in the CSF as shown by India ink stain and positive crytococcal antigen were very high. Delirium and mania were the commonest npm. Hydrocephalus and S/C associated with D and M show higher mortality rate. Appropriate management of raised intracranial pressure in patients with D or M may reduce mortality rate.