Five pediatric patients (including three female and two male) with ages ranged from 2 to 17 years old (average 9-years old). At admission all the patients presented hydrocephalus, and a ventriculoperitoneal shunt (VPS) was subsequently placed. Physical examination revealed low weight in one subject and moderate malnutrition in two cases [Table 1].
All patients showed signs of endocranial hypertension on admission. Sixth nerve palsy was identified in three children and central facial palsy in one case. Seizures were documented in one child, while in another case the patient developed ataxic gait. Three children debuted with hemiparesis; two patients had Parinaud's sign and meningeal signs on admission. Papilledema was found in three patients on fundoscopy. Fever was recorded in only three cases [Table 2].
Preoperative CT scan showed an Evans  index greater than postoperative control MRI (average of 0.39, ranges 0.31-0.58, and 0.30, ranges 0.15-0.31, respectively). Three cases presented asymmetric hydrocephalus (AH) [Figure 1] and abnormalities in the fourth ventricle morphology (cases 2, 4-5). Case 2 developed a isolated fourth ventricle (IFV) [Figure 2]. Case 5 developed compression and displacement of the fourth ventricle secondary to tonsillar displacement and Chiari II malformation [Figure 2c]. In control MRI studies, two children presented cerebral vasculitis (case 2-3). Postsurgical control MRI showed leptomeningeal enhancement (5/5) and basal arachnoiditis (4/5) (involving perimesencephalic cisterns and medial portion of the Sylvian cisterns).
Serological tests in CSF revealed IgG levels from 0.150 to 0.495 D.0. (mean 0.845 D.0. across subjects) while in serum IgG titers ranged from 0.005 to 2.16 D.0. (mean 0.8344). Children with CM diagnosed by serology presented serum IgG levels against Coccidioides >0.500 D.0 with an upper limit of 2.16 D.0. (case 1, 3-4). In contrast, in patients diagnosed by histopathology (cases two and five) titers were <0.150 D.0. and therefore considered negative for systemic coccidiomycosis. Only two patients, with serological diagnosis of CM, presented positive serum IgM titers for Coccidioides (>=0.150 D.0)*.
Mean IgE levels ranged from 25 to 173.UI/ml (mean 0.845 D.0.). Case 5 (patient with Chiari II malformation, who underwent myelomeningocele repair at birth), presented high levels of IgE but did not meet the criteria for Job Syndrome. One patient presented high levels of IgM and in 40% (n = 2) high levels of IgG were observed. The average IgG titers ranged from 1219 to 1858 mg/dl (mean 1522.4 mg/dl). Despite having the highest serum IgG titers, Case 4 antibodies against Coccidioides were not increased (negative test). Hyper or hypogammaglobulinemia was not detected in the rest of cases. T lymphocyte counts were normal in the tested case. No patient presented with eosinophilia or lymphopenia. Serology tests for HIV, hepatitis B and C were negative in all cases.
CSF cytology was positive in two children [Figure 3]. All leptomeningeal biopsies showed inflammation signs, but no spherules were identified. CSF analysis revealed no abnormalities in four subjects; only in one case low glucose levels and mild pleocytosis was detected (see Annex I). All CSF cultures were negative for fungi. Case 2 presented growth for on the distal shunt catheter.
Fluconazole at doses of 6-12 mg/kg/day was prescribed as life-long antifungal therapy. Corticosteroids were indicated in case of cerebral vasculitis, or signs of serious illness. Case 2 was treated with caspofungin and cephalosporins initially due to a positive culture for Pseudomonas aeruginosa in the distal shunt. The child presented neurological deterioration and poor evolution and MRI showed HA, cerebral vasculitis, and IFV. After a month of hospitalization and multiple shunt replacements, C. immitis was isolated in ventricular CSF [Figure 3a] and treatment with Fluconazole 800 mg/day was started. However, the patient presented cardiorespiratory arrest and evolved to a persistent vegetative state.
VPS placement was performed in all subjects. In case of bacterial superinfection, external ventricular drains were also placed (case 2). An average of three surgeries was performed per subject (range 1-9). Case 2 developed IFV and it was therefore decided to place a shunt of the fourth ventricle into the subarachnoid space.
Case 2 presented hyponatremia secondary to transient syndrome of inappropriate antidiuretic hormone secretion (SIHAD), with spontaneous resolution. Cases one and three were initially treated as tuberculous meningitis, but CSF PCR was negative for tuberculosis, and CM was later diagnosed by positive IgG serology against Coccidioides in ventricular CSF. These two children developed rash and drug related hepatitis due to the interaction of fluconazole and the initial antifimic therapy. The average follow-up was 8 months after discharge. Serum IgG and IgM titers against Coccidioides and liver function tests were periodically requested. Control serological tests were reported as negative (<0.150 D.0.). Clinical outcomes were satisfactory in four cases, without evidence of long-term neurological compromise. However, one child (case two) developed a persistent vegetative state. One year after discharge none of the subjects died.