Glenn F. Billman

Acute disseminated encephalomyelitis in childhood: epidemiologic, clinical and laboratory features.

Background: Acute disseminated encephalomyelitis (ADEM) is a central nervous system demyelinating disease that usually follows an apparently benign infection in otherwise healthy young persons. The epidemiology, infectious antecedents and pathogenesis of ADEM are poorly characterized, and some ADEM patients are subsequently diagnosed with multiple sclerosis (MS). Methods: We retrospectively (1991–1998) and prospectively (1998–2000) studied all persons aged < 20 years diagnosed with ADEM from the 3 principal pediatric hospitals in San Diego County, CA, during 1991–2000. Acute neurologic abnormalities and imaging evidence of demyelination were required for study inclusion. Epidemiologic variables, risk factors, clinical course, laboratory and radiographic findings, neuropathology and treatment data were analyzed. Interleukin (IL)-12, interferon-γ(IFN-γ) and IL-10 were assayed in blinded manner on cerebrospinal fluid (CSF) obtained prospectively from a subset of ADEM cases and compared with CSF from patients with enteroviral (EV) meningoencephalitis confirmed by polymerase chain reaction (PCR) and controls without pleocytosis. Results: Data were analyzed on 42 children and adolescents diagnosed with ADEM during 1991–2000, and CSF IL-12, IFN-γ and IL-10 levels were compared among ADEM (n = 14), EV meningoencephalitis (n = 14) and controls without pleocytosis (n = 28). Overall incidence of ADEM was 0.4/100,000/year; incidence quadrupled during 1998–2000 compared with earlier years. No gender, age stratum, ethnic group or geographic area was disproportionately affected. A total of 4 (9.5%) patients initially diagnosed with ADEM were subsequently diagnosed with MS after multiple episodes of demyelination. Although most children eventually recovered, 2 died, including 1 of the 3 ultimately diagnosed with MS. Magnetic resonance imaging was required for diagnosis among 74% of patients; computerized tomography findings were usually normal. Patients with EV had significantly higher mean CSF IFN-γ (P = 0.005) and IL-10 (P = 0.05) than patients with ADEM and controls without CSF pleocytosis. CSF from ADEM patients had CSF cytokine values statistically similar to those of 3 patients subsequently diagnosed with MS. Conclusions: ADEM is a potentially severe demyelinating disorder likely to be increasingly diagnosed as more magnetic resonance imaging studies are performed on patients with acute encephalopathy. Further characterization of the central nervous system inflammatory response will be needed to understand ADEM pathogenesis, to improve diagnostic and treatment strategies and to distinguish ADEM from MS.

Successful treatment of Balamuthia amoebic encephalitis: presentation of 2 cases.

Case histories are presented of 2 individuals (a 5-year-old girl and 64-year-old man) who developed encephalitis caused by the free-living amoeba Balamuthia mandrillaris. Both individuals survived after diagnosis and initiation of effective antimicrobial therapy. Immunostaining for Balamuthia-specific antibody levels identified the causative agent of the infections. Antimicrobial therapy with flucytosine, pentamidine, fluconazole, sulfadiazine, and a macrolide antibiotic (azithromycin or clarithromycin) was initiated. Phenothiazines (thioridazine and trifluoperazine) were also used. Both patients recovered, and there was no evidence of recrudescence of the disease at 2 and 6 years after onset of symptoms. Awareness of Balamuthia as the causative agent of encephalitis and early initiation of antimicrobial therapy were critical to the recovery of both patients. Although optimal antimicrobial therapy for Balamuthia amoebic encephalitis has yet to be determined, the antimicrobials used in these 2 cases effectively controlled the disease. These 2 individuals are the only known survivors of this otherwise fatal type of amoebic encephalitis.

Sudden death in Williams syndrome: Report of ten cases☆☆☆★

Williams syndrome (WS) is a recognizable pattern of malformation with mental retardation, mild growth deficiency, characteristic facies and temperament, and cardiovascular disease. Sudden death is a recognized complication of WS; however, it is thought to be rare. The clinical features of 10 children with WS who died suddenly are reported here, doubling the number of unexpected deaths reported in the literature. We suggest that sudden death is a more common complication than has been assumed previously. Pathologic findings on the seven autopsy cases implicate two anatomic abnormalities that predispose individuals with WS to sudden death: coronary artery stenosis and severe biventricular outflow tract obstruction. The mechanisms for sudden death for both anatomic subgroups include myocardial ischemia, decreased cardiac output, and arrhythmia. We believe these observations warrant the development of strategies for monitoring patients with WS in an attempt to identify those at increased risk of sudden death.

Apparent coagulopathy caused by infusion of shed mediastinal blood and its prevention by washing of the infusate

We found that reinfusion of shed mediastinal blood (SMB) after a cardiac operation was associated with laboratory evidence of disseminated intravascular coagulation. In view of this, we compared the effect of infusing washed or unwashed SMB on the coagulation profiles and blood use of two serial groups of patients undergoing cardiopulmonary bypass. We found that the results of testing for fibrin degradation products converted from negative to positive in 17 of 20 patients who received unwashed SMB versus 1 of 14 patients who received washed SMB (p less than 0.0001). Other coagulation studies did not reveal disseminated intravascular coagulation in either group, nor were there differences in blood use between the two groups. The unwashed SMB contained high titers of fibrin degradation products (mean reciprocal titer = 354 +/- 161) compared with washed SMB (mean reciprocal titer = 34 +/- 18) (p less than 0.01). Based on the volume of SMB infused, the amount of fibrin degradation products in unwashed SMB was sufficient to account for the positive fibrin degradation product assays after infusion in this group. We conclude that infusion of unwashed SMB may confuse the interpretation of tests for disseminated intravascular coagulation or fibrinolysis. As this could lead to unnecessary blood component use and is preventable by washing before infusion, we recommend that the routine infusion of unwashed SMB no longer be employed.

Adenovirus myocarditis: Retrospective diagnosis by gene amplification from formalin-fixed, paraffin-embedded tissues

Understanding the pathogenesis of viral myocarditis is linked to the availability of sensitive assays to detect viruses in clinical material. Recent advances in molecular techniques permit direct detection of viral-specific nucleic acid in tissue samples. This report describes a protocol for DNA extraction and amplification of adenovirus genome from formalin-fixed, paraffin-embedded human tissues that detects as little as 10 copies of viral genome in a background of 0.5 micrograms of human DNA. This sensitive assay permitted the examination of archived tissues to establish a retrospective diagnosis of adenoviral myocarditis in two pediatric patients.

Subcutaneous granuloma annulare: recognition and treatment.

Subcutaneous granuloma annulare (SGA) is a benign inflammatory disorder that occurs in children. The profiles of 12 children with SGA who were diagnosed and treated at our institution were reviewed. The patients presented with a rapidly growing, painless soft-tissue mass of the extremities or scalp. Parental concerns of malignancy and lack of recognition of this condition by the physician led to excessive diagnostic testing and, on occasion, inappropriate therapy. The mean age at presentation was 3.9 years, and the mean follow-up after biopsy study was 3.4 years. The lesions were most commonly located about the elbow, knee, and scalp. While complete blood count, erythrocyte sedimentation rate, and plain radiographs were helpful in ruling out other conditions, no ancillary test was specific for this disorder. In all cases, definitive diagnosis required a biopsy sample. Excisional biopsy was diagnostic but not therapeutic, because 75% of the children had one or more recurrences of this condition at either local or distant sites. Two of the subsequent lesions resolved spontaneously, and no child within the study group has progressed to any recognized systemic illness or connective-tissue disorder.

Nasal hamartoma: case report and review of the literature

Nasal masses in the pediatric population present with nasal obstruction, epistaxis and chronic rhinorrhea. We report on a 6-year-old boy with long-standing nasal obstruction. A large left nasal mass was evident on physical examination and CT scan. Techniques of functional endoscopic sinus surgery were used to resect the mass, which, on pathologic examination, proved to be a hamartoma. Hamartomas are non-neoplastic malformations, or inborn errors of tissue development. They are characterized by an abnormal mixture of tissues indigenous to that area of the body. Review of the literature revealed 5 previously reported cases of nasal hamartomas, only 2 of these in children. Our case is unique in that the hamartoma arose from the ethmoid and maxillary sinuses; previously reported cases arose from the septum and vestibule. This is the first reported case treated using a functional endoscopic sinus surgery approach.

Chondroid hamartoma presenting as a neonatal nasal mass

We present a case of a 3-month-old female with a right nasal mass. Upon evaluation with computed tomography, magnetic resonance imaging and angiography, a large right intranasal mass extending through the cribiform plate, displacing the dura, was noted. The patient underwent a combined midfacial degloving and bifrontal craniotomy for complete resection of the tumor mass. Pathologic evaluation demonstrated a mesenchymal tumor with spindle and stellate cells from which islands of immature cartilage emerged. The spectrum of histologic features closely resembled a mesenchymal chondroid hamartoma typically located in the chest wall. It is the first reported case of a chondroid hamartoma of the head and neck in the literature to date. We examine the characteristics and treatment of this unusual tumor.

Comparison of the Hormonal Response After Bidirectional Glenn and Fontan Procedures

Fluid retention is a frequent complication after the bidirectional Glenn and Fontan procedures. It was our hypothesis that this fluid retention may have a hormonal basis. To test this hypothesis, we made serial determinations of antidiuretic hormone, cortisol, aldosterone, angiotensin, and renin before and after operation in patients undergoing a bidirectional Glenn (n = 15) or Fontan (n = 18) procedure. Patients undergoing a bidirectional Glenn procedure had elevations in antidiuretic hormone, cortisol, and aldosterone immediately after operation. However, none of the hormonal elevations persisted by the fifth postoperative day. In contrast, patients undergoing a Fontan procedure had elevations in antidiuretic hormone, cortisol, aldosterone, renin, and angiotensin II in the immediate postoperative period. Five days postoperatively, the renin and angiotensin II levels remained elevated compared with the preoperative values. The data demonstrate that patients undergoing a bidirectional Glenn procedure and those undergoing a Fontan procedure have different patterns of hormonal response. These results suggest that hormonal factors may contribute to fluid retention after these operations.

Suppression of the Pituitary Thyroid Axis After Cardiopulmonary Bypass in the Neonate

Thyroid hormone has numerous effects on cardiovascular function in the adult. The present study was undertaken to evaluate the effects of cardiopulmonary bypass and deep hypothermia on thyroid function in the neonate. Ten newborns were studied preoperatively and postoperatively. The total and free triiodothyronine, total and free thyroxine, thyroid-stimulating hormone, and thyroglobulin levels were measured by immunoassays. The data demonstrated a transient rise in the free thyroxine level associated with and followed by significant reductions in the free and total triiodothyronine, total thyroxine, thyroid-stimulating hormone, and thyroglobulin levels in the early postoperative period. By the fifth postoperative day, the free and total triiodothyronine and total thyroxine levels were returning toward the preoperative levels under the influence of an elevated thyroid-stimulating hormone level. These results suggest that the combination of cardiopulmonary bypass and deep hypothermia can result in a transient suppression of the pituitary-thyroid axis in the neonate.