Candida meningitis in an infant after abdominal surgery successfully treated with intrathecal and intravenous amphotericin B: A case report.

RATIONALE: Studies on Candida infections in the central nervous system, especially in infants and young children that did or did not have postoperative surgery, are rarely reported. Thus far, intrathecal (i.t.) amphotericin B (AmB) is not routinely recommended as a therapy for Candida meningitis. We report the first case of Candida meningitis in an infant who underwent abdominal surgery and was successfully treated with i.t. and intravenous (i.v.) AmB in the mainland of China. PATIENT CONCERNS: Candida meningitis was confirmed by culture and immunoserological tests in a 1-day-old girl after surgery. She was treated with fluconazole for 1 month, but the patient's symptoms showed no improvement. DIAGNOSES: After surgery, the infant started having recurrent attacks of fever, and laboratory tests of the cerebrospinal fluid (CSF) revealed antigens of Candida tropicalis. CSF tests revealed a high total protein level and a low glucose level. She was diagnosed with a secondary Candida meningitis. INTERVENTIONS: After azole therapy failure, intrathecal and intravenous AmB therapy were used as rescue therapies. OUTCOMES: After nearly 2 months of AmB treatment, all repeat CSF cultures were negative, the infant was deemed stable and was discharged home, and she continued taking voriconazole orally as an outpatient. LESSONS: The combination of i.t. and i.v. administration of AmB can provide a safe and effective alternative to managing this rare but severe disease.

Isolated central nervous system histoplasmosis in an immunocompetent patient: 53-month hiatus to diagnosis and treatment.

Chronic meningitis may result from a wide range of etiologies, both infectious and noninfectious, and is often diagnostically challenging. In most series, tuberculosis remains the most common recognized cause. Of the fungal diseases resulting in chronic meningitis, Cryptococcus is the most common. When untreated, the infectious meningitides typically exhibit an inexorably progressive course with high morbidity and mortality. We report a patient with chronic meningitis due to Histoplasma capsulatum who exhibited a remarkably benign course despite being untreated for the disorder for more than 4 years.

Acute symptomatic seizures in CNS infection.

To determine the frequency and aetiology of acute symptomatic seizures in central nervous system (CNS) infections and to assess the clinical factors predicting the occurrence of the seizures, we retrospectively reviewed the medical records of patients diagnosed with CNS infections from 2000 to 2005. One hundred and forty-seven patients were included in the study. The clinical variables between those with and without acute symptomatic seizures were compared. Of the 147 patients, 23% (34/147) had acute symptomatic seizures. A significant relation between clinical variables and the occurrence of acute symptomatic seizures was found: encephalitis as the aetiology of the CNS infection, Glasgow Coma Scale (GCS) < or =12, and neurological deficits. By multiple logistic regression analysis, age of onset >42 years, encephalitis, and GCS < or =12 were found to be independently significant clinical variables for predicting the occurrence of acute symptomatic seizures. Encephalitis and GCS < or =12 are significant clinical variables for predicting the occurrence of acute symptomatic seizures in CNS infection, suggesting that patients with a greater extent of parenchymal damage are more vulnerable to acute symptomatic seizures.

Diagnostic MR imaging features of craniocerebral Aspergillosis of sino-nasal origin in immunocompetent patients.

BACKGROUND: Craniocerebral invasive Aspergillosis of sino-nasal origin has been reported with a very high mortality due to a peculiarly fulminant clinical course. Early diagnosis based on clinical radiological imaging may have an impact on final clinical outcome. This retrospective study focuses on characteristic MR imaging features of Aspergillosis (of sinonasal origin) in immunocompetent patients. METHODS: Medical records of patients were reviewed retrospectively during the period from 1991 to 2003 in the two tertiary care hospitals. All the patients had radiological evidence of disease in the paranasal sinuses with or without intracranial extension. Immunocompetence of patients was assessed on clinical and radiological data. MRI scans (n=20) were reviewed by both clinical neurosurgeons and neuroradiologists separately. MRI was done on 1.5 tesla scanners and both T2-weighted and T1 weighted sequences were obtained followed gadolinium enhanced images. Patients were categorized into three types based on their anatomical location on MRI scans; type-1 being intracerebral, type-2 as intracranial extradural and type-3 invading orbit and/or skull base only. All these patient had the epicenter of disease in the nose and/or paranasal sinuses as evident on MR imaging. All patients underwent standard surgical intervention followed by antifungal therapy. Clinical outcome was assessed on Glasgow outcome scale with mean duration of clinical follow up of 13.9 months. FINDINGS: Mean age of patents (n=20) was 31.1 years with male preponderance (3:1). MRI scans showed evidence of disease in paranasal sinuses including mucosal thickening (n=11) and complete filling of sinuses (n=9). T2-weighted images showed extremely hypo-intense fungal mass (n=19) while T1-weighted images had iso-intense signals (n=18). Gadolinium-enhanced images showed bright homogenous contrast enhancement (n=18) and peripheral ring enhancement pattern (n=2). All patients underwent appropriated surgical procedures depending upon anatomical location followed by standard antifungal therapy. Tissue diagnoses were established by histopathology (n=20) and culture growth (n=5). Overall mortality remained 15 percent. INTERPRETATION: Craniocerebral Aspergillosis of sinonasal origin has typical MR imaging features. These features include a mass lesion producing hypo-to-iso-intense signals on T1-weighted, extremely low signals (hypo-intense) on T2-weighted images, with bright homogenous enhancement on post-gadolinium T1-weighted imaging. These features in the clinical background may be helpful in early diagnosis and management of Aspergillosis of sino-nasal origin in immunocompetent hosts. Prospective clinical study is required to make firm clinical therapeutic recommendations.

Levels of matrix metalloproteinase-9 within cerebrospinal fluid in a rabbit model of coccidioidal meningitis and vasculitis.

Matrix metalloproteinase (MMP)-9 is produced by the central nervous system and inflammatory cells in a variety of inflammatory conditions in both animals and humans. MMP-9 promotes inflammation, breakdown of the blood-brain barrier, and vasculitis. Because vasculitis is seen frequently in patients with coccidioidal meningitis (CM), this study evaluated the presence of MMP-9 within the cerebrospinal fluid (CSF) of rabbits infected intracisternally with Coccidioides immitis arthroconidia. Infected rabbits demonstrated systemic and neurological sequelae to infection, including CSF pleocytosis. Levels of MMP-9 within CSF were assayed by use of zymography and compared with MMP-2 levels, which served as an internal control. Elevated levels of MMP-9 were detectable by day 3, continued to increase through day 10, and declined by day 15 after infection. MMP-9 may contribute to inflammation and vasculitis in this animal model. Future work can focus on evaluation of MMP inhibitors, to gain a better perspective of the role of this MMP in CM.

Candidal meningitis in neonates: a 10-year review.

Candidal meningitis may complicate systemic candidiasis in the premature neonate. We conducted a 10-year retrospective review of 106 cases of systemic candidiasis in neonates to define the incidence, clinical features, laboratory findings, treatment, and outcome of candidal meningitis. Twenty-three of the 106 neonates had candidal meningitis (0.4% of admissions to the neonatal intensive care unit). The median gestational age was 26.2 weeks, the median birth weight was 820 g, and the median age at the onset of illness was 8 days. Clinical disease was severe and commonly was manifested by respiratory decompensation. Findings of cerebrospinal fluid (CSF) analyses varied: pleocytosis was inconsistent, hypoglycorrhachia was common, gram staining was uniformly negative, and Candida was isolated from 17 neonates (74%). Each infant was treated with amphotericin B (median cumulative dose, 30 mg/kg); 5 also received flucytosine therapy. In conclusion, initial clinical features of candidal meningitis are indistinguishable from those of other causes of systemic infection in premature neonates, and normal CSF parameters do not exclude meningitis. Timely initiation of amphotericin B monotherapy was associated with an excellent outcome.

Coccidioides immitis: Infección primaria del sistema nervioso central. Informe de un caso y revisión de la literatura / Case report and literature review of primary coccidioidal meningitis

Se presenta un caso de meningitis primaria (sin afección pulmonar, ósea o dérmica) por el hongo Coccidioides immitis en un hombre de 27 años de edad que acudió por un síndrome de cráneo hipertensivo de un mes de evolución atendido en nuestra institución. El paciente provenía del norte de California y era previamente sano, sin antecedentes para sospechar inmunodeficiencia. La punción lumbar mostró glucosa 22 mg/dL, proteínas totales 62 mg/dL, leucocitos 110 células/mm3 97 por ciento polimorfonucleares, 3 por ciento mononucleares. La tomografía axial computada de cráneo evidenció dilatación ventricular bilateral. Se hizo el diagnóstico de meningitis por coccidioides immitis mediante la detección de anticuerpos (IgM 6.8 mg/dL e IgG 4.9 mg/dL; normal < 2 mg/dL) y cultivo de líquido cerebroespinal. La radiografía de tórax no mostró alteración alguna. La detección de anticuerpos contra el virus de la inmunodeficiencia humana fue negativa. Se colocó una válvula de derivación ventrículo-peritoneal y se manejó con anfotericina B intravenosa e intratecal a través de un reservorio de Ommaya. A pesar de este tratamiento, el paciente se deterioró neurológicamente y falleció dos semanas después de su egreso en su lugar de origen

Cryptococcal meningitis in human immunodeficiency virus-infected patients in Harare, Zimbabwe.

A prospective observational study was conducted over a 10-month period to determine the clinical and laboratory manifestations of cryptococcal meningitis in Zimbabwe, a country where antifungal agents are not widely available. Eighty-nine patients with cryptococcal meningitis (median age, 34 years; range, 11-63 years; 56 males) were identified from 406 patients for whom a clinical diagnosis of meningitis had been made. All patients tested were positive for antibody to human immunodeficiency virus. Cryptococcal meningitis was the first AIDS-defining illness in 88% of patients. Typical presentations were headache, mental impairment, and meningism (median duration, 14 days; range, 1-180 days). The median CD4+ cell count was 70/microL (range, 0-651/microL). The cumulative median survival from the time of diagnosis was 14 days (range, 0-233 days); 22% of patients survived for >30 days. Independent indicators of a good prognosis were not identified. This study provides a unique basis for the development of novel management strategies for patients with cryptococcal meningitis who reside in resource-poor countries.

Transcranial Doppler sonography at the early stage of acute central nervous system infections in adults.

Transcranial Doppler sonography (TCD) of the middle, anterior and posterior cerebral arteries and of the basilar artery was used to evaluate the mean blood velocity (V mean) and the pulsatility index [PI = (V systolic-V diastolic)/V mean] as a vascular resistance index in 63 patients (male 40, female 23, mean age 43 +/- 19 y) with bacterial meningitis (n = 33, including 2 patients with fungal meningitis) and viral meningitis (n = 30) within 12 h after admission of the patients. The findings were similar for all intracranial arteries. Compared with reference values of 69 healthy volunteers [V mean of middle cerebral artery [MCA] 57 +/- 13 cm/s, MCA-PI 0.83 +/- 0.15], MCA-V mean was increased in patients with Glasgow coma scale (GCS) scores of 14 and 15 (71 +/- 18 cm/s; t-test: p < 0.001), not significantly different in the patients with GCS scores of 10-13 (55 +/- 21 cm/s) and decreased in those with GCS scores of 3-9 (42 +/- 21 cm/s, p < 0.01). The MCA-PI increased from 0.93 +/- 0.22 in the patients with GCS scores of 14-15 to 2.81 +/- 2.06 in those with GCS scores of 3-9 (p < 0.001 vs. controls). By regression analysis, MCA-V mean decreased and MCA-PI increased with decreasing GCS scores (p < 0.001). Only in patients with bacterial meningitis was the Glasgow outcome scale (GOS) score lower the more the MCA-PI was increased (regression analysis p < 0.001). We conclude that in patients with bacterial and viral meningitis, and in a good clinical state, the cerebral blood flow seems increased by hyperemia; with clinical deterioration the cerebral haemodynamics worsen. However, the early assessment of the cerebral blood flow by TCD seems useful for predicting outcome in bacterial meningitis only.