Elizabeth Ford-Jones

Etiology of Acute Childhood Encephalitis at The Hospital for Sick Children, Toronto, 1994–1995

Of 145 patients admitted to our hospital because of encephalitis-like illness, 50 patients hospitalized for > or =72 hours underwent standardized microbiological investigations. A confirmed or probable etiologic agent was identified in 20 cases (40%), including Mycoplasma pneumoniae (9 cases). M. pneumoniae and enterovirus (2), herpes simplex virus (4), Epstein-Barr virus (1), human herpes-virus 6 (HHV-6) (1), HHV-6 and influenza virus type A (1), influenza virus type A (1), and Powassan virus (1). In 13 cases (26%), a possible pathogen was identified, including M. pneumoniae in nine cases. Presenting features included fever (80% of patients), seizures (78%), focal neurological findings (78%), and decreased consciousness (47%). The frequency of findings at the time of admission vs. later in hospitalization was as follows: pleocytosis, 59% vs. 63%; electroencephalogram abnormalities, 87% vs. 96%; and neuroimaging abnormalities, 37% vs. 69%, respectively. The outcomes at the time of discharge were as follows: normal results of physical examination, 32% (16) of the patients; death, 2% (1); motor difficulties, 26% (13); global neurological deficits, 16% (severe, 6; mild, 2); mental status changes, 14% (7); visual defects, 8% (4); and hearing impairment, 2% (1).

Acute Childhood Encephalitis and Mycoplasma pneumoniae

In a prospective 5-year study of children with acute encephalitis, evidence of Mycoplasma pneumoniae infection was demonstrated in 50 (31%) of 159 children. In 11 (6.9%) of these patients, M. pneumoniae was determined to be the probable cause of encephalitis on the basis of its detection in cerebrospinal fluid (CSF) by polymerase chain reaction (PCR) or by positive results of serologic tests for M. pneumoniae and detection of the organism in the throat by PCR. CSF PCR positivity correlated with a shorter prodromal illness (P=.015) and lack of respiratory symptoms (P=.06). Long-term neurologic sequelae occurred in 64% of probable cases. Thirty children (18.9%) who were seropositive for M. pneumoniae but did not have the organism detected by culture or PCR had convincing evidence implicating other organisms as the cause of encephalitis, suggesting that current serologic assays for M. pneumoniae are not sufficiently specific to establish a diagnosis of M. pneumoniae encephalitis.

A 12-Year Prospective Study of Childhood Herpes Simplex Encephalitis: Is There a Broader Spectrum of Disease?

OBJECTIVE. The purpose of this study was to review the experience with herpes simplex encephalitis at the Hospital for Sick Children over the past 12 years. METHODS. All patients who were admitted to our institution with acute encephalitis between January 1994 and December 2005 were enrolled prospectively in an encephalitis registry. Children from the registry with herpes simplex encephalitis were included in this study; we detailed the clinical presentations, laboratory findings, electroencephalographic findings, diagnostic imaging findings, treatments, and outcomes for all cases. RESULTS. Of 322 cases of acute encephalitis, 5% were caused by herpes simplex virus. Initially negative herpes simplex virus cerebrospinal fluid polymerase chain reaction results were found in 2 cases (13%), but results became positive in repeat cerebrospinal fluid analyses. Classic clinical presentations were seen in 75% of cases, cerebrospinal fluid pleocytosis was found in 94%, elevated cerebrospinal fluid protein levels were found in 50%, electroencephalographic changes were observed in 94%, and diagnostic imaging abnormalities were noted in 88%. All patients were treated with intravenous acyclovir. Neurologic sequelae occurred in 63% of cases, including seizures in 44% and developmental delays in 25%. There were no deaths in this study group. CONCLUSIONS. Herpes simplex encephalitis continues to be associated with poor long-term neurologic outcomes despite appropriate therapy. Cerebrospinal fluid polymerase chain reaction results may be negative early in the course of herpes simplex encephalitis; therefore, repeat cerebrospinal fluid analysis should be considered if herpes simplex encephalitis is suspected. Atypical forms of herpes simplex virus central nervous system disease may occur in children.

Acute childhood encephalitis and encephalopathy associated with influenza: a prospective 11-year review.

Background: Influenza virus infection has been associated with a variety of neurologic complications. The objective of this study was to evaluate prospectively the role of influenza viruses in acute childhood encephalitis/encephalopathy (ACE). Methods: All children admitted to the Hospital for Sick Children, Toronto, during an 11-year period with ACE and evidence of acute influenza virus infection were included. Acute influenza virus infection was defined by detection of the organism in the nasopharynx by direct immunofluorescence microscopy or viral culture and/or by a 4-fold or greater rise in complement fixation titer. Results: A total of 311 children with ACE were evaluated; evidence of influenza infection was detected in 7% (22 of 311). Eight were excluded from the main analysis because of evidence implicating other potential pathogens. Eleven of the 14 included subjects were <5 years of age. A respiratory prodrome was documented in 93% of subjects. In 64% neurologic manifestations developed within 5 days of onset of respiratory symptoms. Neuroimaging abnormalities were more common in children <2 years of age. Neurologic sequelae occurred in more than one-half of subjects. Conclusions: In this prospective registry, influenza virus infection was associated with 5% of ACE cases. The majority of children were <5 years of age and the prevalence of neuroimaging abnormalities was higher in children <2 years of age suggesting that younger children are predisposed to the neurologic complications of influenza. An acute rather than a postinfectious process was suggested by the briefness of the respiratory prodrome in most cases.

Measles Inclusion-Body Encephalitis Caused by the Vaccine Strain of Measles Virus

We report a case of measles inclusion-body encephalitis (MIBE) occurring in an apparently healthy 21-month-old boy 8.5 months after measles-mumps-rubella vaccination. He had no prior evidence of immune deficiency and no history of measles exposure or clinical disease. During hospitalization, a primary immunodeficiency characterized by a profoundly depressed CD8 cell count and dysgammaglobulinemia was demonstrated. A brain biopsy revealed histopathologic features consistent with MIBE, and measles antigens were detected by immunohistochemical staining. Electron microscopy revealed inclusions characteristic of paramyxovirus nucleocapsids within neurons, oligodendroglia, and astrocytes. The presence of measles virus in the brain tissue was confirmed by reverse transcription polymerase chain reaction. The nucleotide sequence in the nucleoprotein and fusion gene regions was identical to that of the Moraten and Schwarz vaccine strains; the fusion gene differed from known genotype A wild-type viruses.

Surveillance for Influenza Admissions Among Children Hospitalized in Canadian Immunization Monitoring Program Active Centers, 2003-2004

OBJECTIVES. Influenza is a common childhood infection that may result in hospitalization. Our objectives were to (1) determine characteristics of children hospitalized for influenza and disease manifestations and (2) obtain baseline data before implementation of new recommendations for routine immunization of young children and their caretakers against influenza. METHODS. All of the children hospitalized with laboratory-confirmed influenza at 9 Canadian tertiary care hospitals during the 2003–2004 influenza season were identified from virology laboratory reports, and their charts were reviewed. RESULTS. There were 505 children admitted because of influenza. Fifty-seven percent were <2 years old. Previously healthy children accounted for 58% of all of the cases. Pulmonary and neurologic disorders were the most common underlying chronic conditions. Fever and cough were the most frequent manifestations. Seizures occurred in 9% of cases. Serious complications included myocarditis (2), encephalopathy (6), and meningitis (1). There were 3 influenza-related deaths. Mean duration of hospitalization was 5.3 days. Twelve percent of children required ICU admission, and 6% required mechanical ventilation. Antibiotic therapy was administered in 77% of cases, and 7% received anti-influenza drugs. Information on influenza vaccination was available for 84 of 154 children identified as vaccine candidates. Twenty two had received vaccine, but only 7 children had been fully immunized >14 days before the onset of illness. CONCLUSIONS. Healthy young children and children with chronic conditions are at risk for serious illness with influenza. Ongoing surveillance is needed to evaluate the impact of changing immunization recommendations on the burden of influenza illness in children.

Community-associated MRSA: Superbug at our doorstep

While the potential for a devastating influenza pandemic has captured the imagination of the medical community and the population at large, another epidemic is currently raging in the United States and has already made inroads in Canada.[1][1] Clones of community-associated methicillin-resistant

Time course of juvenile onset recurrent respiratory papillomatosis caused by human papillomavirus.

Background: With the recent licensure of a new quadrivalent vaccine, many diseases caused by human papillomavirus (HPV) can now be prevented, including recurrent respiratory papillomatosis (RRP). The purpose of this study was to describe the burden and time course of juvenile onset RRP. Methods: A retrospective chart review was conducted of children with airway papillomatosis at the Hospital for Sick Children in Toronto, Canada, between 1994 and 2004. Statistical methods included descriptive statistics of the cohort, a repeated events survival model, and nonlinear modeling equations to describe the time course of illness. Results: Nine hundred twenty-six surgical procedures in 67 patients were identified through a review of surgical records. The median age at diagnosis was 3.2 years (range, 0.1–14.8 years) and the most common presenting symptom was hoarseness (75%). Adjuvant pharmacologic therapy (interferon or cidofovir) was used in 13 cases (19%). HPV types 6 or 11 were identified most commonly as the etiologic agent. Nonlinear modeling equations (exponential and quadratic) fit the observed data well, and were superior to linear models. Repeated events survival analysis identified significant prognostic variables: surgeon, adjuvant therapy, and anatomic score. A decision rule is presented that allows the time to next surgery to be predicted based on the previous surgery and the anatomic score. Conclusions: Most patients have a decelerating rate of debulking surgeries over time, well described by our nonlinear modeling equations. Factors affecting the time course of RRP include: intersurgeon variability, the extent and severity of papillomas at the time of laryngoscopy, and the use of adjuvant medical therapies.

VACCINE-STRAIN VARICELLA ZOSTER VIRUS CAUSING RECURRENT HERPES ZOSTER IN AN IMMUNOCOMPETENT 2-YEAR-OLD

Varivax III is a live attenuated vaccine against varicella zoster virus (VZV). We report a case of recurrent vaccine-strain herpes zoster in an immunocompetent 2-year-old child. Vaccine-strain VZV was identified through polymerase chain reaction. This report aims to alert physicians that recurrent vaccine-strain herpes zoster can be a rare complication of VZV vaccination in apparently immunocompetent hosts.

A qualitative study of interphysician telephone consultations: Extending the opinion leader theory

Introduction: It has been suggested that the use of opinion leaders in the dissemination of information may be an effective method of changing clinical practice. Recent reviews on this topic, however, have found mixed results and have concluded that further research is needed to explore the circumstances that effectively utilize opinion leaders. We studied the interphysician telephone consultation, a situation in medical practice in which we see opinion leaders at work, to generate a grounded theory of opinion leader activity. Methods: Data were collected and triangulated among 3 sources: documentation of 129 telephone consultations received, 51 hours of field observations of consultants, and in‐depth interviews of 12 callers and 12 consultants. Analysis was performed using grounded theory methods. Results: A rich description of the context and mechanisms of opinion leader activity emerged. The results describe that opinion leader activity is effective in an informal context in which the practicing physician initiates the exchange. Valuable elements of opinion leader activity that emerged included the provision of a personal touch, reassurance, and advice that blends clinical experience with published evidence. Discussion: Our results suggest that key to effective opinion leader activity is an informal practitioner‐initiated context. Formal didactic sessions led by opinion leaders, therefore, may not be an effective format. In addition to evidence‐based medicine, practicing physicians value “experience‐based medicine” and the personal touch and reassurance that contact with an opinion leader can provide. Using opinion leaders as a means of balancing these 2 paradigms may be a useful model for continuing medical education in this domain.