Neurology October 2009 Volume 73 Issue 16

Background: A causal relationship of common streptococcal infections and childhood neuropsychiatric disorders has been postulated.Objective: To test the hypothesis of an increased rate of streptococcal infections preceding the onset of neuropsychiatric disorders.Methods: Case-control study of a large primary care database comparing the rate of possible streptococcal infections in patients aged 2-25 years with obsessive-compulsive disorder (OCD), Tourette syndrome (TS), and tics with that in controls matched for age, gender, and practice (20 per case). We also examined the influence of sociodemographic factors.Results: There was no overall increased risk of prior possible streptococcal infection in patients with a diagnosis of OCD, TS, or tics. Subgroup analysis showed that patients with OCD had a slightly higher risk than controls of having had possible streptococcal infections without prescription of antibiotics in the 2 years prior to the onset of OCD (odds ratio 2.59, 95% confidence interval 1.18, 5.69; p = 0.02). Cases with TS or tics were not more likely to come from more affluent or urban areas, but more cases lived in areas with a greater proportion of white population (p value for trend = 0.05).Conclusions: The present study does not support a strong relationship between streptococcal infections and neuropsychiatric syndromes such as obsessive-compulsive disorder and Tourette syndrome. However, it is possible that a weak association (or a stronger association in a small susceptible subpopulation) was not detected due to nondifferential misclassification of exposure and limited statistical power. The data are consistent with previous reports of greater rates of diagnosis of Tourette syndrome or tics in white populations.(C)2009AAN Enterprises, Inc.

Objective: To describe the characteristics of children enrolled in treatment trials for neurofibromatosis type 1 (NF1)-related plexiform neurofibroma (PN), PN tumor burden, PN-related complications, and treatment outcomes and to highlight the differences between characteristics of children with NF1 vs children with cancers entered on early phase drug trials.Methods: Pre-enrollment characteristics and complications of PN were retrospectively analyzed in a cohort of 59 children with NF1-related PN treated on 1 of 7 clinical trials at the NIH between 1996 and 2007. Outcome was analyzed in a subset of 19 patients enrolled in phase I trials. Comparisons to children with cancer were made from a similar analysis performed recently.Results: The median age at enrollment was 8 years. The median PN volume was 555 mL. Most patients had no prior chemotherapy or radiation, but nearly half had previous surgery for PN. PN-associated complications and NF1 manifestations were common, including pain (53%), other tumors (18%), and hypertension (8%). Investigational drug therapy was well tolerated. A median of 10 treatment cycles was administered. Patients with NF1-related PN were younger, had better performance score, had less prior therapy, and remained on study longer than cancer patients.Conclusions: Children with NF1-related plexiform neurofibroma (PN) enrolled in clinical trials had large tumors with substantial morbidity. Clinical trials in these children provide information about drug tolerance, cumulative toxicity, and pharmacokinetics in a younger population than early phase pediatric cancer trials. This report may aid in the evaluation of the applicability of traditional pediatric cancer trial designs and endpoints for NF1-related PN.(C)2009AAN Enterprises, Inc.

Background: Co-occurrence of Parkinson disease (PD) and melanoma has been reported in numerous studies. If this was due to common genetic mechanisms, a positive family history of melanoma would be associated with an excessive PD risk, independent of environmental risk factors for PD.Methods: We prospectively examined associations between a family history of melanoma and PD among 157,036 men and women free of PD at baseline (1990 for men and 1982 for women) who participated in 2 ongoing US cohorts: the Health Professional Follow-up Study and the Nurses' Health Study. Information on family history of melanoma in parents or siblings was assessed via questionnaire. Relative risks and 95% confidence intervals were estimated using Cox proportional hazards models and pooled using a fixed-effects model.Results: During 14-20 years follow-up, we identified 616 incident PD cases. A family history of melanoma in a first-degree relative was associated with a higher risk of PD (multivariate relative risk = 1.85; 95% confidence interval: 1.2, 2.8; p = 0.004), after adjusting for smoking, ethnicity, caffeine intake, and other covariates. In contrast, we did not observe significant associations between a family history of colorectal, lung, prostate, or breast cancer and PD risk. Interactions between melanoma family history and age, smoking, or caffeine intake were not significant and subgroup analyses according to these factors generated similar results.Conclusions: Our findings support the notion that melanoma and Parkinson disease (PD) share common genetic components. The genetic determinants of melanoma could therefore be explored as susceptibility candidate genes for PD.(C)2009AAN Enterprises, Inc.

Objective: To determine whether high-sensitivity C-reactive protein (hsCRP) and serum amyloid A (SAA) predict stroke, vascular events, and mortality in a prospective cohort study.Background: Markers of inflammation have been associated with risk of myocardial infarction (MI). Their association with stroke is controversial.Methods: The Northern Manhattan Study includes a stroke-free community-based cohort study in participants aged >=40 years (median follow-up 7.9 years). hsCRP and SAA were measured using nephelometry. Cox proportional hazards models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for the association of markers with risk of ischemic stroke and other outcomes after adjusting for demographics and risk factors.Results: hsCRP measurements were available in 2,240 participants (mean age 68.9 +/- 10.1 years; 64.2% women; 18.8% white, 23.5% black, and 55.1% Hispanic). The median hsCRP was 2.5 mg/L. Compared with those with hsCRP <1 mg/L, those with hsCRP >3 mg/L were at increased risk of ischemic stroke in a model adjusted for demographics (HR = 1.60, 95% CI 1.06-2.41), but the effect was attenuated after adjusting for other risk factors (adjusted HR = 1.20, 95% CI 0.78-1.86). hsCRP >3 mg/L was associated with risk of MI (adjusted HR = 1.70, 95% CI 1.04-2.77) and death (adjusted HR = 1.55, 95% CI 1.23-1.96). SAA was not associated with stroke risk.Conclusion: In this multiethnic cohort, high-sensitivity C-reactive protein (hsCRP) was not associated with ischemic stroke, but was modestly associated with myocardial infarction and mortality. The value of hsCRP and serum amyloid A may depend on population characteristics such as age and other risk factors.(C)2009AAN Enterprises, Inc.

Background: Sleep-related breathing disturbances (SDB) and sleep-wake disturbances (SWD) are often neglected in stroke patients. Recent studies suggest that they are frequent and have an impact on stroke outcome.Methods: We review current knowledge about frequency, clinical presentation, and consequences of poststroke SDB and SWD, and discuss treatment options.Results: SDB, presenting with obstructive, central, or mixed apneas, is present in 50%-70% of stroke patients. We recommend screening for SDB in all stroke patients by respirography. Continuous positive airway pressure (CPAP) is the treatment of choice for obstructive SDB, which reverses the vascular risk of the patients. In the absence of controlled trials, CPAP treatment should be reserved for patients with severe obstructive SDB, daytime symptoms (e.g., sleepiness), or high cardiovascular risk profile. Oxygen and adaptive servoventilation may be used for central SDB. SWD including insomnia, disturbances of wakefulness (hypersomnia, excessive daytime sleepiness, fatigue), sleep-related movement disorders (restless legs syndrome, periodic limb movements during sleep), and parasomnias (REM sleep behavior disorder) are found in 10%-50% of patients. SWD are associated with cognitive disturbances and may compromise neurologic recovery. Hypnotics and sedative antidepressants may aggravate SDB and neurologic recovery and should be used with caution. For disturbances of wakefulness, dopaminergic drugs, modafinil, or activating antidepressants may be considered. Poststroke sleep-related movement disorders can be treated with dopaminergic drugs; REM sleep behavior disorder with clonazepam.Conclusions: Sleep-related breathing disturbances and sleep-wake disturbances are frequent conditions that affect stroke outcome. In view of existing treatment options, these conditions deserve the neurologist's awareness.(C)2009AAN Enterprises, Inc.

(C)2009AAN Enterprises, Inc.