Geoffrey L. Heyer

Consensus Statement on Diagnostic Criteria for PHACE Syndrome

OBJECTIVES: A subgroup of patients with infantile hemangiomas have associated structural anomalies of the brain, cerebral vasculature, eyes, sternum, and/or aorta in the neurocutaneous disorder known as PHACE syndrome. The diagnosis has been broadly inclusive by using a case definition of a facial hemangioma plus ≥1 extracutaneous features, leading to numerous reports of potential associated disease features, many of uncertain significance. This consensus statement was thus developed to establish diagnostic criteria for PHACE syndrome. METHODS: A multidisciplinary group of specialists with expertise in PHACE syndrome drafted initial diagnostic criteria on the basis of review of published, peer-reviewed medical literature and clinical experience. The group then convened in both executive and general sessions during the PHACE Syndrome Research Conference held in November 2008 for discussion and used a consensus method. All conflicting recommendations were subsequently reconciled via electronic communication and teleconferencing. RESULTS: These criteria were stratified into 2 categories: (1) PHACE syndrome or (2) possible PHACE syndrome. Major and minor criteria were determined for the following organ systems: cerebrovascular, structural brain, cardiovascular, ocular, and ventral/midline. Definite PHACE requires the presence of a characteristic segmental hemangioma or hemangioma >5 cm on the face or scalp plus 1 major criterion or 2 minor criteria. Possible PHACE requires the presence of a hemangioma >5 cm on the face or scalp plus 1 minor criterion. The group recognized that it may be possible to have PHACE syndrome with a hemangioma affecting the neck, chest, or arm only or no cutaneous hemangioma at all. In such cases, fulfillment of additional required criteria would also lead to a possible PHACE diagnosis. CONCLUSIONS: These criteria represent current knowledge and are expected to enhance future assessments of PHACE syndrome. It is understood that modifications are to be expected over time to incorporate new research findings.

Predictors of Cerebral Arteriopathy in Children With Arterial Ischemic Stroke Results of the International Pediatric Stroke Study

Background— Cerebral arteriopathies, including an idiopathic focal cerebral arteriopathy of childhood (FCA), are common in children with arterial ischemic stroke and strongly predictive of recurrence. To better understand these lesions, we measured predictors of arteriopathy within a large international series of children with arterial ischemic stroke. Methods and Results— Between January 2003 and July 2007, 30 centers within the International Pediatric Stroke Study enrolled 667 children (age, 29 days to 19 years) with arterial ischemic stroke and abstracted clinical and radiographic data. Cerebral arteriopathy and its subtypes were defined using published definitions; FCA was defined as cerebral arterial stenosis not attributed to specific diagnoses such as moyamoya, arterial dissection, vasculitis, or postvaricella angiopathy. We used multivariate logistic regression techniques to determine predictors of arteriopathy and FCA among those subjects who received vascular imaging. Of 667 subjects, 525 had known vascular imaging results, and 53% of those (n=277) had an arteriopathy. The most common arteriopathies were FCA (n=69, 25%), moyamoya (n=61, 22%), and arterial dissection (n=56, 20%). Predictors of arteriopathy include early school age (5 to 9 years), recent upper respiratory infections, and sickle cell disease, whereas prior cardiac disease and sepsis reduced the risk of arteriopathy. The only predictor of FCA was recent upper respiratory infection. Conclusions— Arteriopathy is prevalent among children with arterial ischemic stroke, particularly those presenting in early school age, and those with a history of sickle cell disease. Recent upper respiratory infection predicted cerebral arteriopathy and FCA in particular, suggesting a possible role for infection in the pathogenesis of these lesions.

The Cerebral Vasculopathy of PHACES Syndrome

Background and Purpose— PHACES syndrome is a neurocutaneous disorder of unknown etiology. We studied the spectrum of associated congenital and progressive cerebral vascular anomalies. Methods— The medical records of 7 patients with PHACES syndrome were reviewed and combined with an additional 108 PHACES cases identified from the literature. We reviewed the clinical characteristics, calculated the relative frequencies of each type of vascular anomaly, and assessed site of vessel involvement relative to hemangioma location. Results— Among a total of 115 PHACES cases, 89 (77.4%) had congenital and/or progressive cerebral vascular anomalies. The most commonly detected congenital arterial anomalies included dysplasia, aberrant origin or course, hypoplasia, and absence or agenesis. Arterial occlusions and stenoses were detected in 24 (20.9%) and 21 (18.3%) cases, respectively. Twenty (17.4%) had persistent embryonic arteries; 15 (13%) had saccular aneurysms. There appears to be a close relation between the regional distributions of cervicofacial hemangiomas and the locations of intracranial and extracranial vascular (and cardiac) anomalies. Conclusion— The vasculopathy of PHACES chiefly comprises a spectrum of congenital and progressive large artery lesions. Based on known embryology and the relative frequencies of specific congenital vascular anomalies, we can predict that the initial cerebral vascular changes occur early in embryogenesis, by the fifth gestational week or earlier. There appears to be both a temporal and a regional link between the arterial anomalies of PHACES and the cutaneous infantile hemangioma.

The Diagnosis and Management of Concussion in Children and Adolescents

BACKGROUND Concussion is a complex brain injury that results in more than 100,000 emergency department visits for school-aged children each year in the United States. All 50 US states have passed concussion legislation designed to promote safety in youth sports. Most of these laws require medical clearance by a licensed health care provider before returning to sport, which may have contributed to an increase in pediatric subspecialty referrals, particularly referrals to the child neurologist. METHODS We reviewed the literature on pediatric concussion. RESULTS This review summarizes the current knowledge and recommendations for concussion diagnosis and management in children and adolescents, athletes and nonathletes. It highlights concussion epidemiology, pathophysiology, advances in neuroimaging, and potential health risks including second impact syndrome and chronic traumatic encephalopathy. It also underscores clinical areas where evidence is lacking. CONCLUSIONS The diagnosis and management of concussion requires specific considerations in children. Further concussion research must be done to minimize injury risk and to optimize medical care for this common problem.

How long is too long? The lack of consensus regarding the post-concussion syndrome diagnosis

Abstract Background/aim: A standard definition of Post-concussion Syndrome (PCS) does not exist. The objective was to determine consensus regarding the definition of PCS among physician members of the American College of Sports Medicine (ACSM). Methods: Physician members of the ACSM were sent an electronic survey to determine opinions regarding the PCS diagnosis. Results: Five hundred and ninety-seven physicians completed the survey. When asked the minimum duration of symptoms required to diagnose PCS, respondents answered: <2 weeks (26.6%), 2 weeks to 1 month (20.4%), 1–3 months (33%) and >3 months (11.1%). Physicians who see ≥10% concussion patients in their practise, as well as physicians whose concussion population consists of >50% paediatric patients, were more likely to require >1 month of symptoms (p < 0.001). When asked the minimum number of symptoms required to diagnose PCS, responses varied: one symptom (55.9%), two symptoms (17.6%), three symptoms (14.6%) and four or more symptoms (3.2%). Respondents from the US were more likely than non-US respondents to require only one symptom for the PCS diagnosis (p = 0.01). Conclusions: There is a lack of consensus regarding the definition of PCS among physician members of the ACSM. A standard definition would improve consistency in concussion research and in clinical practise.

Orthostatic Intolerance and Autonomic Dysfunction in Youth With Persistent Postconcussion Symptoms: A Head-Upright Tilt Table Study.

Objective:To explore head-upright tilt table (HUT) signs of autonomic dysfunction in a cohort of youth with persistent postconcussion symptoms (PCSs) that include light-headedness and to correlate repeat tilt table results with symptom improvements for those patients found to have postural tachycardia syndrome (POTS) on initial testing. Design:Prospective cohort design. Setting:Nationwide Childrens Hospital, Neurology Clinic. Participants:Thirty-four patients (13-18 years of age) with persistent PCSs. Main Outcome Measures:All patients underwent at least 1 tilt table test. The PCS Interview (PCS-I) and patient ratings of light-headedness and vertigo were used to measure symptom burden. Patients found to have POTS were asked to repeat tilt table testing when PCSs improved or 3 to 6 months after the initial test if symptoms persisted. Results:Twenty-four of the 34 (70.6%) patients had abnormal tilt table results with patients categorized as normal (n = 10), isolated syncope (n = 10), and POTS (n = 14). Patients with POTS had higher PCS-I scores than normal patients (P < 0.001) and higher ratings of light-headedness than both normal patients (P = 0.015) and syncope patients (P = 0.04). Twelve POTS patients underwent repeat tilt table testing, and 9 of 12 (75%) no longer met POTS diagnostic criteria. All patients with resolution of POTS had corresponding improvements in PCSs, including light-headedness and vertigo. Conclusions:Our study demonstrates a high rate of tilt table abnormalities among youth with persistent PCSs. Several patients with POTS had normalization of tilt table testing when PCSs improved. These findings warrant further research of autonomic dysfunction related to concussion. Clinical Relevance:Our study is the first to prospectively characterize autonomic dysfunction in patients with persistent PCSs using HUT testing and to show that the tilt test abnormalities normalize in some patients as PCSs improve.

Comparing patient and parent recall of 90-day and 30-day migraine disability using elements of the PedMIDAS and an Internet headache diary

Aim The aim of this article is to compare 90-day and 30-day recall of Pediatric Migraine Disability Assessment (PedMIDAS) elements and headache frequency against daily entries from an Internet headache diary among pediatric patients and their parents. Methods In a prospective cohort study, patients aged 10–18 years with episodic migraine or probable migraine completed a 90-day Internet-based headache diary that incorporated PedMIDAS questions. Following the 90-day diary period, patients and parents completed modified PedMIDAS instruments to assess 90-day and 30-day recall. Intraclass correlation coefficients (ICC) were calculated to measure recall reliability. The Kruskal-Wallis and Jonckheere-Terpstra tests were used to explore recall accuracy as it relates to each participant’s self-reported confidence in recall and to patient age. Results Fifty-two subjects completed 90 consecutive diary entries. Comparing 30-day to 90-day recall of PedMIDAS elements, ICC scores improved by 26.2% (patients) and 17.5% (parents). Patients had better recall than their parents for all study measures. Self-reported confidence in recall and patient age had limited and inconsistent effects on recall accuracy. Conclusion The optimal recall interval to assess migraine disability must balance recall accuracy with generalizability across a range of headache frequencies. When compared to daily diary entries, recall accuracy of PedMIDAS elements and headache frequency improves at 30 days compared to 90 days. Parent report of migraine disability should not be used as a replacement for patient report.

The diagnostic role for susceptibility-weighted MRI during sporadic hemiplegic migraine

Background Hemiplegic migraine is a rare form of migraine with aura that includes motor weakness. Diagnosis during the first episode can be difficult to make and costly, especially with the sporadic form. Cases Our study evaluates the ictal magnetic resonance imaging (MRI) features of four sequential pediatric patients during a first-time, sporadic hemiplegic migraine. Susceptibility-weighted imaging (SWI) revealed cerebral venous prominence and increased magnetic susceptibility affecting brain regions that corresponded with each patient’s neurologic deficits. Repeat MRI (performed in three patients) following migraine recovery demonstrated resolution of all susceptibility abnormalities. Conclusion When combined with conventional MRI sequences, SWI has diagnostic value in the acute setting of motor weakness and with clinical features consistent with hemiplegic migraine. The sequence may help to further characterize ictal cerebral blood flow changes during the hemiplegic migraine aura.

Specific Headache Factors Predict Sleep Disturbances Among Youth With Migraine

BACKGROUND There is a paucity of pediatric data addressing the complex relationship between primary headaches and sleep disturbances. Our study objective was to explore headache-related factors that predict sleep disturbance and to compare sleep complaints with other forms of headache-related disability among youth with migraines. METHODS A prospective cohort study was conducted in patients 10-18 years old with migraine or probable migraine and without daily sleep complaints. The patients completed a 90-day internet-based headache diary. On headache days, patients rated headache intensity, answered Pediatric Migraine Disability Assessment-based questions modified for daily scoring, and reported sleep disturbances that resulted as a direct effect of proximate headaches. RESULTS Fifty-two patients generated 4680 diary entries, 984 patients (21%) involved headaches. Headache intensity (P = 0.009) and timing of headache onset (P < 0.001) were predictive of sleep disturbances. Three Pediatric Migraine Disability Assessment-based items were also associated with sleep disturbances: partial school-day absence (P = 0.04), recreational activities prevented (P < 0.001), and decreased functioning during recreational activities (P < 0.001). Sleep disturbances correlated positively and significantly with daily headache disability scores (rpb = 0.35; P < 0.01). CONCLUSION We conclude that specific headache factors predict sleep disturbances among youth with primary headaches.

Role of Methylenetetrahydrofolate Reductase Gene (MTHFR) 677C>T Polymorphism in Pediatric Cerebrovascular Disorders

Homozygosity for the methylenetetrahydrofolate reductase (MTHFR) 677C>T mutation (MTHFR TT) has been linked to an increased risk for stroke, coronary artery disease, and migraine headaches. The authors analyzed the potential link between MTHFR 677C>T homozygosity and childhood stroke. A true association might facilitate screening, recurrence risk stratification, and treatment in patients with cerebrovascular disease. They performed a retrospective chart review of children tested for the MTHFR 677C>/T mutation; 533 patients underwent MTHFR testing, and 8% were homozygous for the MTHFR 677C>T mutation. There was no difference in the cohort compared with the prevalence in the general population. This suggests that the MTHFR 677 C>T polymorphism played a minimal role or no role in stroke risk. However, the data suggest that the MTHFR TT genotype may influence migraine susceptibility in children because there was a higher proportion of migraine patients (28.6%) with the MTHFR TT homozygous genotype.