Stratification of risk for emergent intracranial abnormalities in children with headaches: a Pediatric Emergency Care Applied Research Network (PECARN) study protocol.

INTRODUCTION: Headache is a common chief complaint of children presenting to emergency departments (EDs). Approximately 0.5%-1% will have emergent intracranial abnormalities (EIAs) such as brain tumours or strokes. However, more than one-third undergo emergent neuroimaging in the ED, resulting in a large number of children unnecessarily exposed to radiation. The overuse of neuroimaging in children with headaches in the ED is driven by clinician concern for life-threatening EIAs and lack of clarity regarding which clinical characteristics accurately identify children with EIAs. The study objective is to derive and internally validate a stratification model that accurately identifies the risk of EIA in children with headaches based on clinically sensible and reliable variables. METHODS AND ANALYSIS: Prospective cohort study of 28 000 children with headaches presenting to any of 18 EDs in the Pediatric Emergency Care Applied Research Network (PECARN). We include children aged 2-17 years with a chief complaint of headache. We exclude children with a clear non-intracranial alternative diagnosis, fever, neuroimaging within previous year, neurological or developmental condition such that patient history or physical examination may be unreliable, Glasgow Coma Scale score<14, intoxication, known pregnancy, history of intracranial surgery, known structural abnormality of the brain, pre-existing condition predisposing to an intracranial abnormality or intracranial hypertension, head injury within 14 days or not speaking English or Spanish. Clinicians complete a standardised history and physical examination of all eligible patients. Primary outcome is the presence of an EIA as determined by neuroimaging or clinical follow-up. We will use binary recursive partitioning and multiple regression analyses to create and internally validate the risk stratification model. ETHICS AND DISSEMINATION: Ethics approval was obtained for all participating sites from the University of Utah single Institutional Review Board. A waiver of informed consent was granted for collection of ED data. Verbal consent is obtained for follow-up contact. Results will be disseminated through international conferences, peer-reviewed publications, and open-access materials.

Patient-reported outcomes of neurologic and neuropsychiatric symptoms in mild COVID-19: a prospective cohort study.

BACKGROUND: Various neurologic manifestations have been reported in patients with COVID-19, mostly in retrospective studies of patients admitted to hospital, but there are few data on patients with mild COVID-19. We examined the frequency and persistence of neurologic/neuropsychiatric symptoms in patients with mild COVID-19 in a 1-year prospective cohort study, as well as assessment of use of health care services and patient-reported outcomes. METHODS: Participants in the Alberta HOPE COVID-19 trial (hydroxychloroquine v. placebo for 5 d), managed as outpatients, were prospectively assessed 3 months and 1 year after their positive test result. They completed detailed neurologic/neuropsychiatric symptom questionnaires, the telephone version of the Montreal Cognitive Assessment (T-MoCA), the Kessler Psychological Distress Scale (K10) and the EuroQol EQ-5D-3L (measure of quality of life). Close informants completed the Mild Behavioural Impairment Checklist (MBI-C) and the Informant Questionnaire on Cognitive Decline in the Elderly. We also tracked use of health care services and neurologic investigations. RESULTS: The cohort consisted of 198 participants (87 female [43.9%] median age 45 yr, interquartile range 37-54 yr). Of the 179 participants with symptom assessments, 139 (77.6%) reported at least 1 neurologic symptom, the most common being anosmia/dysgeusia (99 [55.3%]), myalgia (76 [42.5%]) and headache (75 [41.9%]). Forty patients (22.3%) reported persistent symptoms at 1 year, including confusion (20 [50.0%]), headache (21 [52.5%]), insomnia (16 [40.0%]) and depression (14 [35.0%]); 27/179 (15.1%) reported no improvement. Body mass index (BMI), a history of asthma and lack of full-time employment were associated with the presence and persistence of neurologic/neuropsychiatric symptoms; female sex was independently associated with both (presence: odds ratio [OR] adjusted for age, race, BMI, history of asthma and neuropsychiatric history 5.04, 95% confidence interval [CI] 1.58 to 16.10). Compared to participants without persistent symptoms, those with persistent symptoms had more hospital admissions and family physician visits, and worse MBI-C scores and less frequent independence for instrumental activities at 1 year (83.8% v. 97.8%, p = 0.005). Patients with any or persistent neurologic symptoms had worse psychologic distress (K10 score ≥ 20: adjusted OR 12.1, 95% CI 1.4 to 97.2) and quality of life (median EQ-5D-3L visual analogue scale rating 75 v. 90, p < 0.001); 42/84 (50.0%) had a T-MoCA score less than 18 at 3 months, as did 36 (42.9%) at 1 year. Participants who reported memory loss were more likely than those who did not report such symptoms to have informant-reported cognitive-behavioural decline (1-yr MBI-C score ≥ 6.5: adjusted OR 15.0, 95% CI 2.42 to 92.60). INTERPRETATION: Neurologic/neuropsychiatric symptoms were commonly reported in survivors of mild COVID-19, and they persisted in 1 in 5 patients 1 year later. Symptoms were associated with worse participant- and informant-reported outcomes. Trial registration: ClinicalTrials.gov, no. NCT04329611.

Evaluation of Autonomic Nervous System Dysfunction in Childhood Obesity and Prader-Willi Syndrome.

The autonomic nervous system (ANS) may play a role in the distribution of body fat and the development of obesity and its complications. Features of individuals with Prader-Willi syndrome (PWS) impacted by PWS molecular genetic classes suggest alterations in ANS function; however, these have been rarely studied and presented with conflicting results. The aim of this study was to investigate if the ANS function is altered in PWS. In this case-control study, we assessed ANS function in 20 subjects with PWS (6 males/14 females; median age 10.5 years) and 27 body mass index (BMI) z-score-matched controls (19 males/8 females; median age 12.8 years). Standardized non-invasive measures of cardiac baroreflex function, heart rate, blood pressure, heart rate variability, quantitative sudomotor axon reflex tests, and a symptom questionnaire were completed. The increase in heart rate in response to head-up tilt testing was blunted (p < 0.01) in PWS compared to controls. Besides a lower heart rate ratio with Valsalva in PWS (p < 0.01), no significant differences were observed in other measures of cardiac function or sweat production. Findings suggest possible altered sympathetic function in PWS.

A randomized trial of ketorolac and metoclopramide for migraine in the emergency department.

OBJECTIVE: The objective of this study was to assess the efficacy and safety of a common monotherapy (intravenous [iv] metoclopramide) compared to a combination strategy (adding iv ketorolac to metoclopramide) in children presenting for acute treatment of migraine headache in the emergency department (ED). METHODS: Children aged 5-17 years presenting for acute treatment of migraine headache at two pediatric EDs were enrolled in a double-blind randomized controlled trial. Children were randomly assigned to receive iv metoclopramide 0.2 mg/kg) and placebo or iv metoclopramide (0.2 mg/kg) and ketorolac (0.5 mg/kg). The primary outcome was a mean change in pain from baseline to 120 min via a 100 mm Visual Analog Scale (VAS). Follow-up was conducted 24-h after discharge. RESULTS: Fifty-three children were randomized and included in the analysis (monotherapy group [metoclopramide + placebo], n = 27; and ketorolac group [metoclopramide + ketorolac], n = 26); mean age was 12.9 ± 2.7 years and baseline pain severity on VAS was 67.3 ± 2.7 mm. The mean change in pain intensity at 120 min was -44 mm (SD: 24; 95% confidence interval [CI]: 32-57) for the monotherapy group and -36 mm (SD: 24; 95% CI: 23-49) for the ketorolac group, with a mean difference between groups of 8 mm (95% CI: -9-25; p = 0.360). Seventeen percent of the children (9/53; 95% CI: 7-27%) were pain-free at discharge. There was no difference in headache recurrence or adverse events between groups. CONCLUSIONS: The approach of combining iv metoclopramide with ketorolac failed to improve pain scores in children presenting for acute treatment of migraine headache in the ED compared to metoclopramide monotherapy. Most patients were discharged with residual pain. Further comparative studies are needed to test alternative ED treatments for migraine in children or adolescents.

Familial recurrence of cerebral palsy with multiple risk factors.

The recurrence of cerebral palsy in the same family is uncommon. We, however, report on two families with two or more affected siblings. In both families, numerous potential risk factors were identified including environmental, obstetric, and possible maternal effects. We hypothesize that multiple risk factors may lead to the increased risk of recurrence of cerebral palsy in families. Intrinsic and maternal risk factors should be investigated in all cases of cerebral palsy to properly counsel families on the risk of recurrence. Recent studies of genetic polymorphisms associated with cerebral palsy are considered with reference to our observations in these two families.

Treatment of children with migraine in emergency departments: national practice variation study.

OBJECTIVE: Children with migraine may present to an emergency department (ED) when outpatient management has failed; however, only limited research has examined migraine-abortive medications among children. METHODS: A retrospective chart review of ED presentations for migraine or headache between July 1, 2004, and June 30, 2005, in 10 Canadian pediatric EDs was conducted. A priori, evidence-based treatments were defined as any treatment that was based on high-quality evidence and an absence of opioids as first-line agents. RESULTS: A total of 2515 records were screened, and 1694 (67.4%) met inclusion criteria. The average age of patients was 12.1 years, 14.5% (95% confidence interval [CI]: 12.1%-17.2%) of patients experienced headache >15 days per month, and 62.6% (95% CI: 55.7%-68.9%) had already used migraine-abortive therapy. Significant variations in practice for all classes of migraine-abortive medications were observed. Dopamine receptor antagonists (prochlorperazine, metoclopramide, or chlorpromazine) (39% [95% CI: 28.4%-50.8%]) and orally administered analgesics (acetaminophen and ibuprofen) (24.5% [95% CI: 23.9%-46.8%]) were prescribed most commonly. Predictors for the use of evidence-based treatment included older age (odds ratio: 1.15 [95% CI: 1.07-1.24]) and a discharge diagnosis of migraine (odds ratio: 1.84 [95% CI: 1.11-3.05]). CONCLUSIONS: Children presenting to EDs for treatment often have frequent attacks and have experienced failure of outpatient, migraine-abortive efforts. Practice variations were impressive for the care of children with migraine in these Canadian EDs.

Tuberous sclerosis with open lipped schizencephaly.

Tuberous sclerosis is a multisystem disorder that is transmitted in an autosomal dominant fashion. It affects approximately 1 in 10,000 live births. A growing body of evidence implicates a defect of cell maturation and migration in the pathogenesis of many of the lesions in tuberous sclerosis affecting the central nervous system. There have been numerous case reports of various abnormalities of neuronal migration associated with tuberous sclerosis. To our knowledge, there has only been one case of schizencephaly reported in a patient with tuberous sclerosis. The present report describes a male with tuberous sclerosis and an extensive open lipped schizencephalic cleft affecting his right frontoparietal lobe. This case supports the hypothesis that the cerebral lesions in tuberous sclerosis are secondary to a defect in neuronal maturation and migration.

Neuroimaging features of acute disseminated encephalomyelitis in childhood.

Acute and disseminated demyelination of the central nervous system in children may have many causes. This study reports a retrospective cohort of 10 consecutive pediatric cases (5 to 17 years; mean [S.D.] 12.1 [4.3] years) with a presenting diagnosis of acute disseminated encephalomyelitis and the clinical and radiologic follow-up. The evolution of magnetic resonance imaging abnormalities was determined from serial studies in nine patients with a mean (S.D.) follow-up of 334.2 (312.8) days. Resolution of magnetic resonance imaging T(2) prolongation (i.e., demyelination) within 6 months of presentation was associated most commonly with a final clinical diagnosis of acute disseminated encephalomyelitis (including the multiphasic form), but failed to meet statistical significance (Fisher's exact test; P = 0.083). Incomplete resolution of the magnetic resonance imaging signal abnormalities yielded a statistically significant association (Fisher's exact test; P = 0.048) with an abnormal neurologic outcome. In summary, we conclude that early resolution of magnetic resonance imaging signal abnormalities or recurrent demyelination within 6 months of an acute and disseminated demyelinating event suggests the diagnosis of acute disseminated encephalomyelitis in children, although this association failed to meet statistical significance. However, a statistically significant association between complete resolution of magnetic resonance imaging signal abnormalities and a normal neurologic outcome was observed.

Pediatric meralgia paresthetica.

Meralgia paresthetica is a focal peripheral neuropathy involving the lateral femoral cutaneous nerve and is rarely observed in pediatric practice. Previous reports have highlighted its occurrence within the context of a regional bony malignancy. We present here three patients less than 18 years of age with idiopathic meralgia paresthetica.

Epileptiform abnormalities in children with attention-deficit-hyperactivity disorder.

The proportion of children with attention-deficit-hyperactivity disorder and epileptiform abnormalities is compared with an historic control group of normal school-aged children. The medical records of 655 children 5-16 years of age referred to a single pediatric neurologist (M.S.) from January 1991 to December 1999 with school problems, behavior problems, or hyperactivity were retrospectively reviewed. Clinical criteria for attention-deficit-hyperactivity disorder were satisfied in 476 of these children. An electroencephalogram was obtained from 347 patients and coded as epileptiform in 6.1 +/- 1.3%, which is significantly higher (chi-square test, P < 0.025) than the prevalence rate of 3.5 +/- 0.6% observed in a study of 3,726 normal school-aged children. The epileptiform abnormality was present only with activation procedures in six of our patients (hyperventilation [n = 2] and photic stimulation [n = 4]). Only three of the 21 children with epileptiform abnormalities developed a seizure disorder in our cohort. We conclude that the prevalence rate of epileptiform abnormalities is greater in children with attention-deficit-hyperactivity disorder compared with that observed in normal school-aged children when hyperventilation and photic stimulation are used. However, the clinical utility of routine electroencephalography in the diagnosis of a comorbid seizure disorder in children with attention-deficit-hyperactivity disorder is limited.