Lori Billinghurst

Canadian Guidelines for the Evidence-Based Treatment of Tic Disorders: Pharmacotherapy:

This article seeks to provide the practising clinician with guidance on the pharmacological management of tic disorders in children and adults. We performed a systematic review of the literature on the treatment of tic disorders. A multi-institutional group of 14 experts in psychiatry, child psychiatry, neurology, pediatrics, and psychology engaged in a consensus meeting. The evidence was presented and discussed, and nominal group techniques were employed to arrive at consensus on recommendations. A strong recommendation is made when the benefits of treatment clearly outweigh the risks and burdens, and can apply to most patients in most circumstances without reservation. With a weak recommendation, the benefits, risks, and burdens are more closely balanced, and the best action may differ depending on the circumstances. Based on these principles, weak recommendations were made for the use of pimozide, haloperidol, fluphenazine, metoclopramide (children only), risperidone, aripiprazole, olanzapine, quetiapine, ziprasidone, topiramate, baclofen (children only), botulinum toxin injections, tetrabenazine, and cannabinoids (adults only). Strong recommendations were made for the use of clonidine and guanfacine (children only). While the evidence supports the efficacy of many of the antipsychotics for the treatment of tics, the high rates of side effects associated with these medications resulted in only weak recommendations for these drugs. In situations where tics are not severe or disabling, the use of a medication with only a weak recommendation is not warranted. However, when tics are more distressing and interfering, the need for tic suppression to improve quality of life is stronger, and patients and clinicians may be more willing to accept the risks of pharmacotherapy.

Cerebral Venous Sinus (Sinovenous) Thrombosis in Children

Cerebral venous sinus (sinovenous) thrombosis (CSVT) in childhood is a rare, but underrecognized, disorder, typically of multifactorial etiology, with neurologic sequelae apparent in up to 40% of survivors and mortality approaching 10%. There is an expanding spectrum of perinatal brain injury associated with neonatal CSVT. Although there is considerable overlap in risk factors for CSVT in neonates and older infants and children, specific differences exist between the groups. Clinical symptoms are frequently nonspecific, which may obscure the diagnosis and delay treatment. While morbidity and mortality are significant, CSVT recurs less commonly than arterial ischemic stroke in children. Appropriate management may reduce the risk of recurrence and improve outcome, however there are no randomized controlled trials to support the use of anticoagulation in children. Although commonly employed in many centers, this practice remains controversial, highlighting the continued need for high-quality studies. This article reviews the literature pertaining to pediatric venous sinus thrombosis.

Canadian Guidelines for the Evidence-Based Treatment of Tic Disorders: Behavioural Therapy, Deep Brain Stimulation, and Transcranial Magnetic Stimulation:

This clinical guideline provides recommendations for nonpharmacological treatments for tic disorders. We conducted a systematic literature search for clinical trials on the treatment of tics. One evidence-based review (including 30 studies) and 3 studies on behavioural interventions, 3 studies on deep brain stimulation (DBS), and 3 studies on transcranial magnetic stimulation (TMS) met our inclusion criteria. Based on this evidence, we have made strong recommendations for the use of habit reversal therapy and exposure and response prevention, preferably embedded within a supportive, psychoeducational program, and with the option to combine either of these approaches with pharmacotherapy. Although evidence exists for the effcacy of DBS, the quality of this evidence is poor and the risks and burdens of the procedure are fnely balanced with the perceived benefts. Our recommendation is that this intervention continues to be considered an experimental treatment for severe, medically refractory tics that have imposed severe limitations on quality of life. We recommend that the procedure should only be performed within the context of research studies and by physicians expert in DBS programming and in the management of tics. There is no evidence to support the use of TMS in the treatment of tics. However, the procedure is associated with a low rate of known complications and could continue to be evaluated within research protocols. The recommendations we provide are based on current knowledge, and further studies may result in their revision in future.

Quality improvement in neurology: Child neurology quality measure set: Executive summary

Childhood neurologic disorders, as a group, include relatively common conditions such as migraine (prevalence between 3% and 10.6% in children 3–15 years of age1,2), transient tic disorders (TDs) (3%),3 and specifically Tourette syndrome (TS) (0.8%),3 and rarer disorders such as infantile spasms that may occur in only about 1,200 infants each year in the United States. These disorders account for a disproportionately higher number of emergency department visits, intensive care admissions, deaths, and higher costs when compared to other childhood illness.4 Generally, delivery of quality care should improve outcomes and result in decreased unnecessary utilization of health services.4

Cerebral sinus venous thrombosis in a child with hyperthyroidism.

To the Editor: The influence of thyroid dysfunction on hemostasis has been suggested [1]. Evidence for this association is provided by recent larger adult studies showing an increased risk of venous thrombosis and pulmonary embolism with hyperthyroidism [2,3]. We report a novel finding of cerebral sinus venous thrombosis (CSVT) in a child with symptomatic hyperthyroidism and heterozygosity for factor V Leiden. An 8-year-old previously healthy female presented with a 3-week history of weight loss, intermittent vomiting, headaches, and photophobia; the body mass index was 10 kg/m (<5th percentile). A head CT scan showed an extensive CSVT (Fig. 1A,B). Treatment with low molecular weight heparin (Enoxaparin) was initiated, but was changed to unfractionated heparin due to interval propagation of the thrombus (Fig. 1C). Potential predisposing factors for developing CSVT included, dehydration, elevated coagulation factors VIII (2.5 IU/ml), IX (1.66 IU/ml), XI (1.97 IU/ml), fibrinogen (6.3 g/L) and confirmed heterozygosity for factor V Leiden. Levels for protein C, protein S, antithrombin, lipoprotein (a), lupus anticoagulant, anticardiolipin antibodies, and the prothrombin and MTHFR gene analysis were normal. An episode of tachycardia

Attention and executive functioning profiles in children following perinatal arterial ischemic stroke

ABSTRACT Perinatal arterial ischemic stroke (PAIS) is a form of childhood stroke; the majority of those affected experience neurologic sequelae, including motor, language and neurocognitive impairments. This study examines the attention and executive functioning (EF) profiles of children following PAIS, as well as the impact of age and sex. In this single-center cross-sectional study, 40 children aged 3 to 16 years (median age 7.2 years; 58% male) who have suffered a PAIS underwent a comprehensive neuropsychological battery to assess attention and EF. Parents completed behavioral questionnaires regarding real-world functioning. Composite scores were calculated for seven attention and EF domains (Attention, Working Memory, Verbal Retrieval, Inhibitory Control, Flexibility/Shifting, Planning/Organization, and Processing Speed). The results for all measured domains of attention and EF are significantly lower in the participants compared to the normative samples (p < .001), with the exception of Working Memory. However, increasing difficulty with Working Memory is associated with developing age. Older age at time of testing is also associated with a higher incidence of clinically-elevated attention deficit hyperactivity disorder (ADHD) symptoms. Sex is not associated with performance measures or parental report of functioning. The participants demonstrate mild-to-moderate attention and EF impairment compared to the normative population. Clinicians, families, and educators should be informed about the neurocognitive sequelae of PAIS and the need for close developmental surveillance in this population to identify vulnerable children and initiate appropriate therapeutic interventions in a timely fashion.

Incidence and predictors of epilepsy after pediatric arterial ischemic stroke.

Objective: To determine the cumulative incidence and clinical predictors of remote symptomatic seizures and epilepsy after pediatric arterial ischemic stroke (AIS). Methods: We performed a retrospective analysis of 218 participants with neonatal AIS (NAIS), presumed perinatal AIS (PPAIS), and childhood AIS (CAIS) from a single-center prospective consecutive cohort enrolled from 2006 to 2014. Medical records were reviewed for timing, semiology, and treatment of acute symptomatic seizures, remote symptomatic seizures (RSS), and epilepsy. Cumulative incidence of RSS and epilepsy were assessed using survival analysis. Results: Acute symptomatic seizures occurred in 94% of NAIS (n = 70/74) and 17% of CAIS (n = 18/105). Younger children were more likely to present with seizures at stroke ictus, and acute symptomatic seizures were predictive of later RSS and epilepsy in CAIS. Median follow-up for the entire cohort was 34 months, interquartile range 44.9 months (16.3–61.2). Estimated cumulative incidence of RSS at 2 years was 19% in NAIS, 24% in PPAIS, and 7% in CAIS. Estimated cumulative incidence of epilepsy at 2 years was 11% in NAIS, 19% in PPAIS, and 7% in CAIS. The median time to these outcomes was <2 years in all stroke subtypes. Among participants developing epilepsy (n = 34), seizures were often well-controlled at last follow-up with median Engel class of ≤2 (<1 seizure/month). Conclusions: RSS and epilepsy are important neurologic sequelae of pediatric AIS. Children with perinatal stroke and CAIS with acute symptomatic seizures are at increased risk of these outcomes. These cohorts need further study to identify biomarkers and potential therapeutic targets for epileptogenesis.

Degos disease mimicking primary vasculitis of the CNS.

A 4-year-old boy developed a headache. Initial evaluation revealed a normal neurologic examination and a right subdural hygroma on CT. Worsening headaches led to hospitalization at an outside institution. MRI showed leptomeningeal enhancement; magnetic resonance angiography (MRA) was normal. Infectious, rheumatologic, hematologic, and CSF studies were unrevealing. He then developed a left-sided hemiparesis. Imaging showed increased leptomeningeal enhancement with punctate infarcts in the right hemisphere. CT angiography demonstrated irregularity involving branches of the circle of Willis suggestive of vasculitis. Methylprednisolone (30 mg·kg−1·d−1 × 5 days) was administered for presumed CNS vasculitis.

Incidence of Recurrence in Posterior Circulation Childhood Arterial Ischemic Stroke

Importance Childhood arterial ischemic stroke (CAIS) affects approximately 1.6 per 100 000 children per year, while stroke recurs in up to 20% of patients at 5 years. Factors determining the risk of recurrence are incompletely understood. Objective To investigate the incidence of the recurrence of CAIS in the posterior and anterior circulations to determine if the risk differs between the 2 locations. Design, Setting, and Participants A retrospective analysis of CAIS was conducted among children enrolled in a single-center prospective consecutive cohort at The Children’s Hospital of Philadelphia between January 1, 2006, and January 1, 2015. Children with confirmed CAIS occurring between 29 days and 17.99 years were evaluated for inclusion. Patients were excluded if infarcts were located in both the anterior and posterior distributions or if CAIS occurred as a complication of intracranial surgery or brain tumor. Main Outcomes and Measures Stroke recurrence. Results The study population included 107 patients (75 boys [70.1%] and 32 girls [29.9%]; median age at AIS, 7.7 years [interquartile range, 3.1-13.6 years]). Sixty-one children had anterior circulation CAIS (ACAIS) and 46 had posterior circulation CAIS (PCAIS). Median follow-up was 20.9 months (interquartile range, 8.7-40.4 months). For ACAIS, recurrence-free survival was 100% at 1 month and 96% (95% CI, 85%-99%) at 1 and 3 years. For PCAIS, recurrence-free survival was 88% (95% CI, 75%-95%) at 1 month and 81% (95% CI, 66%-90%) at 1 and 3 years. The hazard ratio for recurrence after PCAIS compared with ACAIS was 6.4 (95% CI, 1.4-29.8; P = .02) in univariable analysis and 5.3 (95% CI, 1.1-26.4; P = .04) after adjusting for sex and cervical dissection. Conclusions and Relevance We identified a subgroup of patients that comprise more than 80% of recurrences of CAIS. Three years after incident stroke, 19% of children with PCAIS had a recurrence compared with 4% of patients with ACAIS. Different mechanisms of stroke may account for this difference. Children with PCAIS may warrant increased monitoring. This study highlights the necessity for further research focused on recurrence prevention.

Drugs for treating acute migraine headaches in children and adolescents

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To describe and assess the evidence from controlled trials on the efficacy and tolerability of pharmacological interventions by any route of administration versus placebo or other drug treatments for acute attacks of migraine in children.