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1.
J Clin Neurosci ; 79: 137-143, 2020 Sep.
Article in English | MEDLINE | ID: mdl-33070883

ABSTRACT

Moyamoya is a progressive cerebrovascular arteriopathy that affects children of any age. The goal of this study was to determine imaging and clinical outcomes as well as complication rates in a pediatric cohort undergoing either a combined direct/indirect or indirect-only revascularization approach. Patients with moyamoya disease or syndrome ≤ 18 years of age at the time of initial surgery were identified, and clinical data were collected retrospectively. Over a 12-year period, 26 patients underwent revascularization procedures on 49 hemispheres with a median follow-up of 2.6 years from surgery. Median age at surgery was 7.3 years (range 1.4-18.0 years). Thirty-three hemispheres (67.3%) underwent combined revascularization with a direct bypass and encephalomyosynangiosis, and sixteen hemispheres (32.7%) underwent indirect-only revascularization. The rate of 30-day perioperative complication was 10.2%, and the rate of postoperative clinical stroke by end of follow-up was 10.2% by hemisphere. There was a 5.7% rate of intraoperative bypass failure requiring conversion to an indirect revascularization approach. On follow-up imaging, 96.9% of direct bypasses remained patent. On multivariate analysis, higher preoperative Pediatric Stroke Outcome Measure (PSOM) scores were associated with lower rates of good clinical outcome on follow-up (unit OR 0.03; p = 0.03). Patients with age < 5.4 years had lower rates of good clinical outcome on follow-up. In this North American cohort, both combined direct/indirect and indirect only revascularization techniques were feasible. However, younger children < 5.4 years of age have worse outcomes than older children, similar to east Asian cohorts.


Subject(s)
Cerebral Revascularization/methods , Moyamoya Disease/surgery , Treatment Outcome , Adolescent , Cerebral Revascularization/adverse effects , Child , Child, Preschool , Cohort Studies , Female , Humans , Infant , Male , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Retrospective Studies , Stroke/epidemiology , Stroke/etiology , Syndrome
2.
Curr Pain Headache Rep ; 22(3): 17, 2018 Feb 23.
Article in English | MEDLINE | ID: mdl-29476266

ABSTRACT

PURPOSE OF REVIEW: Headache phenotypes can differ between adults and children. While most headaches are due to primary headache disorders, in a small population, they can be an indication of a potentially life-threatening neurologic condition. The challenge lies in identifying warning signs that warrant further workup. This article reviews different types of pediatric headaches and headache evaluation in children and teens, and focuses on the approach for diagnosis of secondary headaches. RECENT FINDINGS: Common thought is that increased frequency and severity of headache may reflect secondary pathology; however, headache phenotype may not be fully developed and can evolve in adolescence or adulthood. Headache location, particularly occipital headache alone, does not necessarily signify secondary intracranial pathology. Certain warning signs warrant neuroimaging, but others only warrant imaging in certain clinical contexts. Brain MRI is the neuroimaging modality of choice, though there is a high rate of incidental findings and often does not change headache management. A stepwise approach is essential to avoid missing secondary headaches. There are several differences between adults and children in clinical manifestations of headache. Evaluation and diagnosis of pediatric headache starts with a thorough headache and medical history, family and social history, and identification of risk factors. A thorough physical and neurologic exam is important, with close attention to features that could suggest secondary headache pathology. Neuroimaging and other testing should only be performed if there is concern for secondary headache.


Subject(s)
Headache/diagnosis , Adolescent , Child , Female , Headache/etiology , Humans , Male
3.
Neuropharmacology ; 77: 285-93, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24157491

ABSTRACT

Adolescence is a sensitive developmental period for limbic and dopamine systems that coincides with the typical age for onset of tobacco use. We have previously shown that a 4-day, low-dose nicotine (0.06 mg/kg) pretreatment enhances locomotor and penile response to the D2-like agonist, quinpirole (0.4 mg/kg), in adolescent but not adult rats. The present study is designed to determine mechanisms underlying this effect. Nicotine enhancement of adolescent quinpirole-induced locomotion was mediated by D2 receptors (D2Rs) since it was blocked by the D2R antagonist, L-741,626, but not by the D3R and D4R antagonists, NGB 2904 and L-745,870. Enhancement of quinpirole-induced erectile response was blocked by both L-741,626 and NGB 2904, indicating involvement of D3Rs. Whereas D2R binding was unaffected by adolescent nicotine pretreatment, effector coupling in the striatum was increased, as determined by GTPγS binding. Nicotine pretreatment enhanced quinpirole-induced c-fos mRNA expression in the hypothalamic paraventricular and supraoptic nuclei in adolescents only. Adolescent nicotine pretreatment enhanced c-fos mRNA expression in corticotropin releasing factor (CRF) cells of the paraventricular nucleus, and enhancement of penile erection was blocked by the CRF-1 receptor antagonist, CP 376,396. These findings suggest that adolescent dopamine and CRF systems are vulnerable to alteration by nicotine. This is the first evidence for a role of CRF in adolescent erectile response.


Subject(s)
Dopamine Agonists/pharmacology , Hypothalamus/drug effects , Nicotine/pharmacology , Quinpirole/pharmacology , Receptors, Dopamine D2/metabolism , Animals , Dopamine Antagonists/pharmacology , Dose-Response Relationship, Drug , Hypothalamus/metabolism , Male , Motor Activity/drug effects , Penile Erection/drug effects , Proto-Oncogene Proteins c-fos/metabolism , Rats , Rats, Sprague-Dawley
4.
Neuropsychopharmacology ; 36(7): 1319-31, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21412223

ABSTRACT

Epidemiological studies have shown that adolescent smoking is associated with health risk behaviors, including high-risk sexual activity and illicit drug use. Using rat as an animal model, we evaluated the behavioral and biochemical effects of a 4-day, low-dose nicotine pretreatment (60 µg/kg; intravenous) during adolescence and adulthood. Nicotine pretreatment significantly increased initial acquisition of cocaine self-administration, quinpirole-induced locomotor activity, and penile erection in adolescent rats, aged postnatal day (P)32. These effects were long lasting, remaining evident 10 days after the last nicotine treatment, and were observed when nicotine pretreatment was administered during early adolescence (P28-31), but not late adolescence (P38-41) or adulthood (P86-89). Neurochemical analyses of c-fos mRNA expression, and of monoamine transmitter and transporter levels, showed that forebrain limbic systems are continuing to develop during early adolescence, and that this maturation is critically altered by brief nicotine exposure. Nicotine selectively increased c-fos mRNA expression in the nucleus accumbens shell and basolateral amygdala in adolescent, but not adult animals, and altered serotonin markers in these regions as well as the prefrontal cortex. Nicotine enhancement of cocaine self-administration and quinpirole-induced locomotor activity was blocked by co-administration of WAY 100 635 (N-{2-[4-(2-methoxyphenyl)-1-piperazinyl] ethyl}-N-(2-pyridinyl)cyclohexanecarboxamide), a selective serotonin 1A (5-HT1A) receptor antagonist. Early adolescent pretreatment with the mixed autoreceptor/heteroceptor 5-HT1A receptor agonist, 8-OH-DPAT, but not the autoreceptor-selective agonist, S-15535, also enhanced quinpirole-induced locomotor activation. Nicotine enhancement of quinpirole-induced penile erection was not blocked by WAY 100 635 nor mimicked by 8-OH-DPAT. These findings indicate that early adolescent nicotine exposure uniquely alters limbic function by both 5-HT1A and non-5-HT1A receptor mechanisms.


Subject(s)
Limbic System/drug effects , Nicotine/pharmacology , Nicotinic Agonists/pharmacology , Receptor, Serotonin, 5-HT1A/metabolism , 3,4-Dihydroxyphenylacetic Acid/metabolism , 8-Hydroxy-2-(di-n-propylamino)tetralin/pharmacology , Age Factors , Analysis of Variance , Animals , Animals, Newborn , Autoradiography/methods , Catecholamines/metabolism , Dopamine Agonists/pharmacology , Drug Administration Schedule , Drug Interactions , Gene Expression Regulation/drug effects , Locomotion/drug effects , Male , Piperazines/pharmacology , Protein Binding/drug effects , Quinpirole/pharmacology , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Receptor, Serotonin, 5-HT1A/genetics , Reward , Self Administration/methods , Serotonin Plasma Membrane Transport Proteins/genetics , Serotonin Plasma Membrane Transport Proteins/metabolism , Serotonin Receptor Agonists/pharmacology , Time Factors
5.
Pharmacol Biochem Behav ; 96(1): 82-90, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20423718

ABSTRACT

Since adolescence is a critical period for the initiation of tobacco use, we have systematically compared behavioral and endocrine responses to nicotine in Sprague-Dawley rats of both sexes at early adolescence (postnatal day (P) 28), mid- adolescence (P38) and adulthood (P90). Locomotion and center time in a novel open field were evaluated for 30min following intravenous injection of saline or nicotine (60microg/kg), followed by measurement of plasma corticosterone. Complex age and sex differences in behavioral and endocrine response were observed, which were dependent on the functional endpoint examined. Whereas there were age differences in nicotine effects on all functional measures, sex differences were largely restricted to adult stress-related corticosterone and center-time responses. Although significant drug effects were detected at P28 and P90, there was no effect of nicotine at P38 on any measure examined. In saline-treated males, but not females, there were significant positive correlations across age between initial ambulatory counts and both initial vertical counts and total center time. Nicotine treatment increased correlations in both sexes, and yielded a significant negative interaction between initial ambulatory counts and plasma corticosterone. The unique responses of adolescents to nicotine are consistent with an immature function of nicotinic acetylcholine receptors at this age.


Subject(s)
Motor Activity/drug effects , Motor Activity/physiology , Nicotine/pharmacology , Stress, Psychological/blood , Age Factors , Animals , Corticosterone/blood , Female , Male , Rats , Rats, Sprague-Dawley
6.
Psychopharmacology (Berl) ; 207(1): 143-52, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19727678

ABSTRACT

RATIONALE: Epidemiological evidence of early adolescent tobacco use, prior to that of marijuana and other illicit drugs, has led to the hypothesis that nicotine is a "gateway" drug that sensitizes reward pathways to the addictive effects of other psychostimulants. OBJECTIVE: To test this hypothesis, we have compared the effect of a brief, low-dose nicotine pretreatment of adolescent and adult rats on subsequent locomotor response to acute and chronic cocaine. MATERIALS AND METHODS: Adolescents, aged postnatal day (P) 28, and adults, aged P86, were given four daily injections of saline or nicotine (0.06 mg/kg, i.v.). At P32 and P90, rats were given acute injections of cocaine (0, 0.4 or 1.0 mg/kg, i.v.) and monitored for locomotor activity in either a habituated or novel test environment. To examine cocaine sensitization, rats were treated for 3 days with saline or cocaine (0.4 mg/kg, i.v.), and, after 1 day of withdrawal, were given a challenge dose of cocaine (0.4 mg/kg, i.v.). RESULTS: Nicotine pretreatment did not affect acute, drug-induced locomotor activity at either age. However, age differences in cocaine response were observed, with adolescent animals showing enhanced locomotor activity in the novel environment. Adolescent controls did not exhibit cocaine-induced locomotor sensitization, whereas adults did. Nicotine pretreatment during adolescence promoted the development and expression of a sensitized response to repeated cocaine exposure similar to that observed in saline-pretreated adult controls. CONCLUSIONS: These findings show that brief pretreatment with nicotine, in a low dose comparable to that inhaled in 2-4 cigarettes, enhances cocaine-induced behavioral plasticity in adolescent rats.


Subject(s)
Adaptation, Physiological/drug effects , Aging , Cocaine/pharmacology , Dopamine Uptake Inhibitors/pharmacology , Nicotine/pharmacology , Nicotinic Agonists/pharmacology , Analysis of Variance , Animals , Animals, Newborn , Dose-Response Relationship, Drug , Exploratory Behavior/drug effects , Locomotion/drug effects , Male , Rats , Rats, Sprague-Dawley
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