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Arterial ischemic strokes (AIS) are the most frequent neurologic sequela encountered in patients with cardiac myxomas. Although most of these AIS are thrombotic in nature, occasionally embolized tumor fragments may be responsible for the ischemic damage.1 Most patients with cardiac myxoma are women between the third and the sixth decade of life, who present with one or more symptoms of the classic triad (hemodynamic instability due to intracardiac obstruction, systemic embolization, and constitutional symptoms).1 Carney complex is an inherited disorder characterized by myxomas that often present earlier in life. We present a 12-year-old girl who developed a pediatric AIS (PAIS) due to the direct embolization of cardiac myxomatous tissue fragments in the setting of Carney complex. We discuss the clinical presentation, case-specific differential diagnosis, and workup, followed by epidemiology, pathophysiology, treatment, and prognosis of AIS resulting from cardiac myxomas.

BACKGROUND Although the genetic load is high in early-onset Parkinson's disease, thorough investigation of the genetic diagnostic yield has yet to be established. The objectives of this study were to assess variants in known genes for PD and other movement disorders and to find new candidates in 50 patients with early-onset PD. METHODS We searched for variants either within genes listed by the International Parkinson and Movement Disorder Society Task Force on Genetic Nomenclature or rare homozygous variants in novel candidate genes. Further, exome data from 1148 European PD patients (International Parkinson Disease Genomics Consortium) were used for association testing. RESULTS Seven patients (14%) carried pathogenic or likely pathogenic variants in Parkin, PLA2G6, or GBA. In addition, rare missense variants in DNAJC13:p.R1830C and in PPM1K:p.Y352C were detected. SPG7:p.A510V and PPM1K:p.Y352C revealed significant association with PD risk (P

Objective: The objective of this exploratory study is to describe communication between physicians and the actor parent of a standardized 8-year-old patient in respiratory distress who was nearing the end of life. Methods: Thirteen pediatric emergency medicine and pediatric critical care fellows and attendings participated in a high-fidelity simulation to assess physician communication with an actor-parent. Results: Fifteen percent of the participants decided not to initiate life-sustaining technology (intubation), and 23% of participants offered alternatives to life-sustaining care, such as comfort measures. Although 92% of the participants initiated an end-of-life conversation, the quality of that discussion varied widely. Conclusion: Findings indicate that effective physician–parent communication may not consistently occur in cases involving the treatment of pediatric patients at the end of life in emergency and critical care units. Practice Implications: The findings in this study, particularly that physician–parent end-of-life communication is often unclear and that alternatives to life-sustaining technology are often not offered, suggest that physicians need more training in both communication and end-of-life care.

The objective of this study was to characterize the changes in adverse events, seizure severity, and frequency in response to a pharmaceutical formulation of highly purified cannabidiol (CBD; Epidiolex®) in a large, prospective, single-center, open-label study. We initiated CBD in 72 children and 60 adults with treatment-resistant epilepsy (TRE) at 5 mg/kg/day and titrated it up to a maximum dosage of 50 mg/kg/day. At each visit, we monitored treatment adverse events with the adverse events profile (AEP), seizure severity using the Chalfont Seizure Severity Scale (CSSS), and seizure frequency (SF) using seizure calendars. We analyzed data for the enrollment and visits at 12, 24, and 48 weeks. We recorded AEP, CSSS, and SF at each follow-up visit for the weeks preceding the visit (seizures were averaged over 2-week periods). Of the 139 study participants in this ongoing study, at the time of analysis, 132 had 12-week, 88 had 24-week, and 61 had 48-week data. Study retention was 77% at one year. There were no significant differences between participants who contributed all 4 data points and those who contributed 2 or 3 data points in baseline demographic and AEP/SF/CSSS measures. For all participants, AEP decreased between CBD initiation and the 12-week visit (40.8 vs. 33.2; p 0.0001) with stable AEP scores thereafter (all p ≥ 0.14). Chalfont Seizure Severity Scale scores were 80.7 at baseline, decreasing to 39.2 at 12 weeks (p 0.0001) and stable CSSS thereafter (all p ≥ 0.19). Bi-weekly SF decreased from a mean of 144.4 at entry to 52.2 at 12 weeks (p = 0.01) and remained stable thereafter (all p ≥ 0.65). Analyses of the pediatric and adult subgroups revealed similar patterns. Most patients were treated with dosages of CBD between 20 and 30 mg/kg/day. For the first time, this prospective, open-label safety study of CBD in TRE provides evidence for significant improvements in AEP, CSSS, and SF at 12 weeks that are sustained over the 48-week duration of treatment.

Objective: We report a child presenting with spinal myelopathy secondary to H3K27M mutant diffuse midline glioma. Case Report: A 4-year-old boy presented with a 3-week history of progressive gait difficulty. Examination revealed bilateral hand and lower extremity weakness, left leg hypertonia with ankle clonus, and a right hemisensory deficit. Magnetic resonance imaging of neuroaxis showed cervical and thoracic spinal cord with expansion and irregular areas of enhancement. Serum and cerebrospinal fluid studies were unremarkable for infectious, autoimmune, inflammatory, and neoplastic causes but showed mild cerebrospinal fluid pleocytosis, hypoglycorrhachia, and high protein level. A thoracic cord biopsy revealed a diffuse midline glioma (World Health Organization grade IV). Consequently, the tumor involved intracranial structures and patient died within 4 months after diagnosis. Conclusion: High-grade spinal cord gliomas are very rare but should be considered in the differential diagnosis of pediatric myelopathy. Tissue biopsy is recommended in indeterminate cases to facilitate diagnosis and to guide management.

Mirror movements usually seen in the Klippel-Feil syndrome are most commonly appreciated in the upper extremities. Lower extremity involvement is seen rarely and when observed, is found in conjunction with upper extremity mirror movements. We report what we believe to be the first case of mirror movements found exclusively in the lower extremities in a female patient presenting with tethered cord syndrome. Our hopes are that this report will help elucidate mechanisms involved with these anomalous movements, as currently there is no commonly accepted etiology.

Paroxysmal dyskinesias are rare movement disorders. The onset of paroxysmal dyskinesias in childhood are typically idiopathic (sporadic or familial), whereas those in adulthood are usually secondary to an identifiable cause. Paroxysmal dyskinesias are classified according to precipitating factors, and these include paroxysmal kinesigenic dyskinesia, paroxysmal nonkinesigenic dyskinesia, paroxysmal exertion-induced dyskinesia, and paroxysmal hypnogenic dyskinesia. The pathophysiology remains unknown; however, there is increasing evidence that channelopathies may play a role, which explains the response to anticonvulsant medications in certain kindreds. Pharmacologic treatment with anticonvulsant medications, clonazepam, tetrabenazine, trihexyphenidyl, or levodopa is reviewed herewith. Paroxysmal dyskinesias go by many names, but a rational classification does exist. Of those that respond to medications, the majority of paroxysmal dyskenesias respond to anticonvulsant medications. Channelopathies have been implemented as a cause in paroxysmal dyskinesias.

A 13-year-old girl presented with abnormal movements occurring during sleep, consisting of stiffening of the limbs bilaterally and random flailing of the arms and legs lasting less than 1 minute several times per night (video on the Neurology ® Web site at [Neurology.org][1]). Daytime episodes were reported, but rare. After workup, she was given a diagnosis of paroxysmal hypnogenic dyskinesia (PHD), was started on oxcarbazepine, and became free of episodes. PHD typically occurs during non-REM sleep1; spells are short in duration but may cause fragmented sleep. There is no established treatment and medical management is based on treatment of other more common paroxysmal dyskinesias. [1]: http://www.neurology.org/

This chapter describes the experiences of a multidisciplinary clinic specializing in the diagnosis and management of Chiari 1 malformations (C1M). Data were collected regarding reasons for referral and outcomes and indicate that approximately half of referred patients were appropriately diagnosed radiographically with CIM. Moreover, of patients who actually had consistent imaging, only about one-third reported symptoms attributable to C1M. These findings illustrate pertinent issues relating to health-care resources and delivery of multidisciplinary care.

Previous work has shown that medication errors related to anticonvulsants are common during the transition into the hospital for pediatric patients. The purpose of this work was to evaluate whether children with epilepsy admitted for reasons other than epilepsy experience nonoptimal care in anticonvulsant medication management preceding the occurrence of seizures. Using a retrospective cohort of children with epilepsy admitted for reasons other than epilepsy, we created timelines from data in the medical record for the children who experienced seizures. These timelines included the timing and concentration of anticonvulsant administration and seizure occurrence. Three child neurologists independently identified whether nonoptimal care preceded the occurrence of seizures and potentially contributed to the occurrence of the seizure. Of 120 children, 18 experienced seizures and 12 experienced nonoptimal care in anticonvulsant management preceding seizure occurrence. Nonoptimal care that occurred during the transition into the hospital included missed doses of anticonvulsants, delays in administration during which seizures occurred, and patients inadvertently not receiving their home dosing of medication. Anticonvulsant medication errors are known to occur during the transition into the hospital. Here we present a case series of children who experienced nonoptimal care in anticonvulsant medication management who subsequently experienced seizures. Further work to identify how likely the outcome of seizures is following anticonvulsant medication errors, specifically focusing on timing as well as interventions to change the system issues that lead to these errors, is indicated.

Three neurodegenerative diseases, Huntington's disease (HD), Kennedy's disease (hereditary spinobulbar muscular atrophy, SBMA), and type 1 spinocerebellar ataxia (SCA-1) have been found to share a common genetic defect: an unstable region of repeated CAG trinucleotides which are thought to be translated into a polyglutamine moiety. The unstable repeat regions occur near the N-termini of the predicted proteins for HD and SBMA, but the location of the CAG repeat region is not known for SCA-1. Each disease is notable for a relatively circumscribed region of central nervous system pathology, and the lack of predicted similarity of the abnormal proteins makes a common mechanism related to the function of each protein unlikely. In order to reconcile the similar genetic abnormalities with the disparities in phenotypes, we suggest a common thread with regard to the pathogenesis of neuronal death. We hypothesize that the mechanism of neurotoxicity in these diseases occurs not through the production of abnormal proteins, but by the generation of abnormal posttranslational cleavage products. These products, in part consisting of abnormally large polyglutamine moieties, act to disturb the cellular and mitochondrial milieu such that energy metabolism is impaired, rendering specific regions of the nervous system vulnerable, and resulting in the clinical phenotypes of HD, SBMA, and SCA-1. We offer this interpretation of recent genetic findings from a neurobiologic perspective, in addition to suggesting testable hypotheses concerning potential disease mechanisms.

Juvenile neuronal ceroid lipofuscinosis (JNCL; CLN3 disease; Batten disease) is an autosomal recessive neurodegenerative disease of childhood. Symptoms typically present at school age with vision loss followed by progressive cognitive decline, motor dysfunction, seizures, and behavior problems. Studies on sex differences in JNCL have yielded mixed results, but parent anecdotes suggest that females experience a more precipitous disease course. Therefore, we sought to determine if sex-based differences exist in JNCL. We used data from the Unified Batten Disease Rating Scale (UBDRS), the Batten Disease Support and Research Association (BDSRA) database, and the PedsQL quality of life (QoL) survey to evaluate sex-based differences in functional independence and time from symptom onset to death. On average, females had JNCL symptom onset one year later and death one year earlier than did males. Despite a later age at onset, females had lower functional capability, earlier loss of independent function, and lower physical QoL. Future research in sex differences in JNCL may help to further understand the biological mechanisms underpinning the disease course and may point to targeted therapies.

Objective The objective of this blinded, prospective, longitudinal study was to determine whether new group A β hemolytic streptococcal (GABHS) infections are temporally associated with exacerbations of tic or obsessive-compulsive (OC) symptoms in children who met published criteria for pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). A group of children with Tourette syndrome and/or OC disorder without a PANDAS history served as the comparison (non-PANDAS) group. Method Consecutive clinical ratings of tic and OC symptom severity were obtained for 31 PANDAS subjects and 53 non-PANDAS subjects. Clinical symptoms and laboratory values (throat cultures and streptococcal antibody titers) were evaluated at regular intervals during a 25-month period. Additional testing occurred at the time of any tic or OC symptom exacerbation. New GABHS infections were established by throat swab cultures and/or recent significant rise in streptococcal antibodies. Laboratory personnel were blinded to case or control status, clinical (exacerbation or not) condition, and clinical evaluators were blinded to the laboratory results. Results No group differences were observed in the number of clinical exacerbations or the number of newly diagnosed GABHS infections. On only six occasions of a total of 51 (12%), a newly diagnosed GABHS infection was followed, within 2 months, by an exacerbation of tic and/or OC symptoms. In every instance, this association occurred in the non-PANDAS group. Conclusions This study provides no evidence for a temporal association between GABHS infections and tic/OC symptom exacerbations in children who meet the published PANDAS diagnostic criteria.

Tremor in childhood is not commonly described in the literature; but it is also likely underappreciated. The etiology of childhood tremor encompasses a wide variety of pathologic processes. Tremor may occur in isolation, or in association with other neurologic findings or systemic disorders. This article aims to provide an overview of tremorogenic mechanisms with respect to neuroanatomy and neurophysiology, particularly as they relate to children. Classification of tremors, diagnostic entities in childhood, and treatment will also be discussed. With improved recognition and characterization of childhood tremors, we may gain a better understanding of the pathophysiology of the disease and determine more age-appropriate treatment strategies.

The authors describe a pediatric patient with repaired hypoplastic left heart syndrome developing protein-losing enteropathy, hypocalcemia, vitamin D deficiency, and hemichorea. After correction of nutritional vitamin D deficiency with calcium and vitamin D supplementation, the chorea resolved. Hypoalbuminemia also improved after the correction of vitamin D deficiency without requiring albumin infusions. This report also raises the possible role of calcium or vitamin D in the intestinal loss of albumin in protein-losing enteropathy.

MECP2 mutations mainly occur in females with Rett syndrome. Mutations have been described in 11 boys with progressive encephalopathy: seven of nine with affected sisters and two de novo. The authors report four de novo occurrences: three pathogenic and one potentially pathogenic. Common features include failure to thrive, respiratory insufficiency, microcephaly, and abnormal motor control. MECP2 mutations should be assessed in boys with progressive encephalopathy and one or more of respiratory insufficiency, abnormal movements or tone, and intractable seizures.

We obtained information about the behavioral, psychiatric, and functional status of 26 children (13 males, 13 females) with juvenile neuronal ceroid lipofuscinosis (JNCL; mean age 12y 3mo [SD 3y 4mo]; range 6y 9mo to 18y 8mo). Twenty-five children had visual impairment and 18 were known to have a positive seizure history before enrollment. Parents completed the Child Behavior Checklist, Scales of Independent Behavior - Revised, and a structured interview to assess obsessive-compulsive symptoms. Participants exhibited a broad range of behavioral and psychiatric problems, rated as occurring frequently and/or as severe in more than half of the sample. Males and females did not differ with regard to the number of behavioral and psychiatric problems. Children were also limited in their ability to perform activities of daily living, including self-care, hygiene, socialization, and other age-appropriate tasks. Results provide a quantitative baseline for behavioral and psychiatric problems and functional level in JNCL, against which further decline can be measured. Longitudinal assessment of behavioral and psychiatric symptoms and functional abilities is continuing and will provide much-needed data on the natural history of JNCL.

Approximately 5% of new essential tremor (ET) cases arise during childhood. The goal of the current report was to examine the possible association between male gender and pediatric ET, using data from 95 pediatric ET cases seen at three medical centers (two in the United States and one in Spain). The odds of ET in our sample of cases were threefold higher in boys compared to girls. Whether this association between male gender and pediatric ET represents a selection bias or a true gender-mediated biological difference in disease expression is not known, although some data support the latter possibility.

With prospects improving for experimental therapeutics aimed at postponing the onset of illness in preclinical carriers of the Huntington's disease (HD) gene, we assessed agreement among experienced clinicians with respect to the motor manifestations of HD, a relevant outcome measure for preventive trials in this population. Seventy-five clinicians experienced in the evaluation of patients with early HD and six non-clinicians were shown a videotape compiled from the film archives of the United States–Venezuela Collaborative HD Research Project. Observers were asked to rate a 2–3-minute segment of the motor examination for each of 17 at-risk subjects. The rating scale ranged from 0 (normal) to 4 (unequivocal extrapyramidal movement disorder characteristic of HD). As measured by a weighted κ statistic, there was substantial agreement among the 75 clinicians in the judgment of unequivocal motor abnormalities comparing scale ratings of 4 with ratings that were not 4 (weighted κ = 0.67; standard error (SE) = 0.09). Agreement among the non-clinicians was only fair (weighted κ = 0.28; SE = 0.10). Even under the artificial conditions of a videotape study, experienced clinicians show substantial agreement about the signs that constitute the motor manifestations of illness in subjects at risk for HD. We expect these findings to translate to a similar level of interobserver agreement in the clinical trial setting involving experienced investigators examining live patients. © 2005 Movement Disorder Society

The authors present a case of a child with epilepsy who developed choreoathetotic movements coinciding with the development of epilepsia partialis continua. His abnormal movements and seizures resolved after successful management of his epilepsia partialis continua with intravenous immunoglobulin and steroid therapy. The authors propose that the chorea was an unusual manifestation of epilepsia partialis continua.

Purpose To emphasize that papilledema and other ophthalmic manifestations may occur in the syndrome of headache, neurologic deficits, and cerebrospinal fluid lymphocytosis (HaNDL). Design Two interventional case reports. Methods Two patients were seen with ophthalmologic findings, including decreased vision, papilledema, sixth nerve palsy, and a variety of neurologic deficits. Each underwent cerebrospinal fluid analysis and intracranial pressure measurement by spinal tap and neuroimaging studies to confirm the diagnosis of HaNDL. Results Both patients received acetazolamide to lower intracranial pressure. The first patient had complete resolution of signs and symptoms. The second, who was also given systemic corticosteroids, was left with diminished visual acuity in the right eye with nasal visual field loss and optic atrophy. Conclusions The diagnosis of HaNDL is one of exclusion, which must be made in conjunction with a neurologist. HaNDL may be accompanied by elevated intracranial pressure and papilledema. As in other disorders causing papilledema, these patients may have permanent visual sequelae. Recognition by the ophthalmologist of this rarely reported syndrome will facilitate prompt patient diagnosis and treatment.

We report medullary injury during adenoidectomy in two children who received injections of local anesthetic agents into the operative bed. Initial manifestations included hemiparesis, nystagmus, and ataxia. Magnetic resonance imaging showed hemorrhagic, paramedian medullary lesions in both patients. The mechanism of injury is likely to be injection of fluid into the medulla.

Bartonella quintana is a fastidious Gram-negative bacillus first identified as a cause of a febrile illness, trench fever, among troops engaged in World War I.1 Infection with this agent in immunocompetent hosts, after an incubation period of 5 to 20 days, may result in one of four clinical patterns: 1) 4- to 5-day febrile illness, 2) periodic febrile illness with three to eight episodes lasting 4 to 5 days each, 3) prolonged febrile illness, or 4) afebrile bacteremia.2 Associated symptoms are nonspecific and include headache, conjunctivitis, maculopapular rash, organomegaly, arthralgias, myalgias, and bone pain (shin bone fever). The infection is globally endemic, and outbreaks are associated with poor sanitation and hygiene. There is no known nonhuman reservoir, and the body louse Pediculus humanus is the only known vector.1Infection of immunocompromised hosts with B quintana or B henselae has been associated with angioproliferative disease of the skin and internal organs, including cutaneous bacillary angiomatosis3-6 and bacillary peliosis of the spleen, liver, bone marrow, and central nervous system (CNS).7-10Endocarditis has also been reported in this population.11-13 We report two cases of CNS disease associated with B quintana . The patient in case 1 presented with a granulomatous process involving the right thalamus and surrounding tissues, and in case 2 with encephalopathy without evidence of focal involvement. B quintana was identified from the cerebrospinal fluid (CSF) by polymerase chain reaction (PCR), with nucleotide sequencing demonstrating >99% homology with a segment of the B quintana citrate synthase gene segment. These two cases represent distinctive CNS pathology and broaden the clinical spectrum of B quintana infection. ### Case 1 A 19-year-old male presented to the emergency room with a complaint of frontal headache, left-side weakness, and slurred speech. Over a period of several weeks, the patient had developed clumsiness and …

The Cooperative Huntington Observational Research Trial (COHORT) is an observational study designed to collect information in order to learn more about Huntington disease (HD), potential treatments, and to plan future research studies of experimental drugs aimed at postponing the onset or slowing the progression of HD. The study includes both adults and children who have been clinically diagnosed with HD and adults who are part of an HD family. Study visits occur once a year and typically include a neurological examination, family history information, a blood draw for genotyping, and the collection of biological samples for future HD research. There is increasing interest in enrolling older teenagers (age 15-17 years) who are at risk for HD into COHORT. In order to gauge interest in this change in protocol, a survey was designed to gather information about attitudes toward this expansion of COHORT on the part of the members of the Huntington Study Group (HSG), many of whom are currently participating in the COHORT study. The survey was posted online, and HSG members were invited to complete the survey. Answers to questions were collected on a five point Likert scale that ranged as follows: Strongly Disagree, Disagree, Neutral, Agree, Strongly Agree. Respondents were asked whether it was important for affected individuals, unaffected members of HD families, and children to participate in research. They were also asked to imagine that they were members of a family affected with HD and whether they would agree to their own child's participation in an observational trial that included (1) a neurological exam and (2) a blood sample draw for the purposes of DNA analysis for research. Respondents were also asked what their major concerns might be concerning their own or their child's participation. Results of this survey will be presented.

In a double-blind study of influenza in a population of college students in 1984, ribavirin small-particle aerosol treatment of 38 patients (18 treated, 20 control) infected with a new antigenic variant, influenza virus strain A/Victoria/7/83 (H1N1), was associated with statistically significant reductions in the height and duration of fever, systemic symptoms, and virus shedding. Patients received a total of 2.4 g of ribavirin over 42 h during 68 h of hospitalization without any side effects. In addition, in a study of patients infected with influenza virus strain B/Texas/1/84 (seven treated, eight control) treated with ribavirin aerosol showed a trend of more rapid recovery than control patients.

We reviewed the recent experience at Texas Children's Hospital by examining the records of 11 children who underwent suboccipital decompression for symptomatic Chiari type I malformation. Presenting complaints included neck pain (1 child), scoliosis (4 children), back pain (1 child), torticollis (1), motor dysfunction (1), and apnea (3 children). Neurologic findings were normal in 7 of the 11 children. The craniocervical junction and medulla were studied by magnetic resonance imaging, which revealed anatomy consistent with Chiari type I malformation in all cases. At surgery, all patients had tonsillar herniation to the first cervical vertebra or below. Three patients had syringomyelia. Postoperatively, either the patients were symptom free or, in the cases of scoliosis and torticollis, there was no progression. Our experience suggests that Chiari type I malformation may occur in childhood with varied and unusual clinical findings. Magnetic resonance imaging was essential to the diagnosis; the presence of tonsillar herniation was confirmed at surgery. The results of suboccipital decompression were favorable in this series.

The treatment of children with attention deficit hyperactivity disorder (ADHD) and Tourette syndrome (TS) has been problematic because methylphenidate (MPH)--the most commonly used drug to treat ADHD--has been reported to worsen tics and because clonidine (CLON)--the most commonly prescribed alternative--has unproven efficacy.The authors conducted a multicenter, randomized, double-blind clinical trial in which 136 children with ADHD and a chronic tic disorder were randomly administered CLON alone, MPH alone, combined CLON + MPH, or placebo (2 x 2 factorial design). Each subject participated for 16 weeks (weeks 1-4 CLON/placebo dose titration, weeks 5-8 added MPH/placebo dose titration, weeks 9-16 maintenance therapy).Thirty-seven children were administered MPH alone, 34 were administered CLON alone, 33 were administered CLON + MPH, and 32 were administered placebo. For our primary outcome measure of ADHD (Conners Abbreviated Symptom Questionnaire--Teacher), significant improvement occurred for subjects assigned to CLON (p0.002) and those assigned to MPH (p0.003). Compared with placebo, the greatest benefit occurred with combined CLON + MPH (p0.0001). CLON appeared to be most helpful for impulsivity and hyperactivity; MPH appeared to be most helpful for inattention. The proportion of individual subjects reporting a worsening of tics as an adverse effect was no higher in those treated with MPH (20%) than those being administered CLON alone (26%) or placebo (22%). Compared with placebo, measured tic severity lessened in all active treatment groups in the following order: CLON + MPH, CLON alone, MPH alone. Sedation was common with CLON treatment (28% reported moderate or severe sedation), but otherwise the drugs were tolerated well, including absence of any evident cardiac toxicity.Methylphenidate and clonidine (particularly in combination) are effective for ADHD in children with comorbid tics. Prior recommendations to avoid methylphenidate in these children because of concerns of worsening tics are unsupported by this trial.