Methods: The study included 305,468 participants of the NIH-AARP Diet and Health cohort, of whom 1,662 had a PD diagnosis after 1995. We estimated odds ratios (OR) and 95% confidence intervals from multivariate logistic regression models.

Results: Compared with never smokers, the multivariate ORs were 0.78 for past smokers and 0.56 for current smokers. Among past smokers, a monotonic trend toward lower PD risk was observed for all indicators of more smoking. Stratified analyses indicated that smoking duration was associated with lower PD risk within fixed intensities of smoking. For example, compared with never smokers, the ORs among past smokers who smoked >20 cigarettes/day were 0.96 for 1–9 years of smoking, 0.78 for 10–19 years, 0.64 for 20–29 years, and 0.59 for 30 years or more (p for trend = 0.001). In contrast, at fixed duration, the typical number of cigarettes smoked per day in general was not related to PD risk. Close examination of smoking behaviors in early life showed that patients with PD were less likely to be smokers at each age period, but if they smoked, they smoked similar numbers of cigarettes per day as individuals without PD.

Conclusions: This large study suggests that long-term smoking is more important than smoking intensity in the smoking–Parkinson disease relationship.

Methods: PET with ¹⁸fluorodopa (FDOPA), N-¹¹C-methyl-4-piperidyl acetate (MP4A), and ¹⁸fluorodeoxyglucose (FDG) was performed in 8 patients with PDD, 6 patients with DLB, and 9 patients with PD without dementia vs age-matched controls. Data were analyzed with voxel-based statistical parametric mapping and region of interest–based statistics.

Results: We found a reduced FDOPA uptake in the striatum and in limbic and associative prefrontal areas in all patient groups. Patients with PDD and patients with DLB showed a severe MP4A and FDG binding reduction in the neocortex with increasing signal diminution from frontal to occipital regions. Significant differences between PDD and DLB were not found in any of the radioligands used. Patients with PD without dementia had a mild cholinergic deficit and no FDG reductions vs controls.

Conclusions: Patients with dementia with Lewy bodies and Parkinson disease dementia share the same dopaminergic and cholinergic deficit profile in the brain and seem to represent 2 sides of the same coin in a continuum of Lewy body diseases. Cholinergic deficits seem to be crucial for the development of dementia in addition to motor symptoms. The spatial congruence of cholinergic deficits and energy hypometabolism argues for cortical deafferentation due to the degeneration of projection fibers from the basal forebrain.

Methods: Twenty-nine consecutive patients with atraumatic convexal subarachnoid hemorrhage were identified using International Classification of Diseases–9 code from 460 patients with subarachnoid hemorrhage evaluated at our institution over a course of 5 years. Retrospective review of patient medical records, neuroimaging studies, and follow-up data was performed.

Results: There were 16 women and 13 men between the ages of 29 and 87 years. Two common patterns of presentations were observed. The most frequent presenting symptom in patients ≤60 years (n = 16) was a severe headache (n = 12; 75%) of abrupt onset (n = 9; 56%) with arterial narrowing on conventional angiograms in 4 patients; 10 (p = 0.003) were presumptively diagnosed with a primary vasoconstriction syndrome. Patients >60 years (n = 13) usually had temporary sensory or motor symptoms (n = 7; 54%); brain MRI scans in these patients showed evidence of leukoaraiosis and/or hemispheric microbleeds and superficial siderosis (n = 9; 69%), compatible with amyloid angiopathy (n = 10; p < 0.0001). In a small group of patients, the presentation was more varied and included lethargy, fever, and confusion. Four patients older than 60 years had recurrent intracerebral hemorrhages in the follow-up period with 2 fatalities.

Conclusion: Convexal subarachnoid hemorrhage is an important subtype of nonaneurysmal subarachnoid bleeding with diverse etiologies, though a reversible vasoconstriction syndrome appears to be a common cause in patients 60 years or younger whereas amyloid angiopathy is frequent in patients over 60. These observations require confirmation in future studies.

Methods: We analyzed our database of all patients with MS followed up at the Marshfield Multiple Sclerosis Center.

Results: Among the 1,078 patients, there were 2,587 relapses (mean of 2.4 per patient, with a range of 1–11 attacks over 1–15 years). Only 7 patients had a relapse resulting in EDSS ≥6 that did not recover. Genetic analysis showed no difference in HLA-DR or NOS2A loci between these patients and other MS populations, nor were there any clinical factors that identified high risk. Two of these patients were on interferon treatment at the time of their disabling attack.

Conclusions: The fear of a sudden irreversible disability should not influence therapeutic decisions because such attacks are very rare and can occur whether or not patients are treated with interferons.

Background: Early-onset cases of neurologic diseases often reflect increased biologic predisposition, specific risk factors, or both.

Methods: Of 2,173 children identified as the target sample, consents were obtained from 1,870 (86.0%), and analyzable data were provided by 1,547 (71.2%). Parents and children were interviewed using a questionnaire consisting of 97 questions, with a validated headache module (10 questions). Crude and adjusted prevalences of HFEH (10–14 headache days per month) and CDH (15 or more headache days per month) were calculated.

Results: The prevalence of CDH was 1.68% (girls 2.09%, boys 1.33%). The overall prevalence of HFEH was 2.52% (girls 2.8%, boys 2.3%). After adjusting for gender, age, parental history of headaches, income, and school of origin, the prevalence of CDH was higher in girls than in boys (2.2% vs 1.1%, p < 0.01) and in nonwhite vs white children (2.2% vs 1.2%, p < 0.01). Similar differences were seen for HFEH (girls 3.1%, boys 2.0%, p < 0.01), (nonwhite 3.1%, white 1.9%, p < 0.01). Income significantly contributed to the model.

Conclusion: High-frequency episodic headaches and chronic daily headaches are common in the preadolescent pediatric population. Health care providers and educators should be aware of the magnitude of the problem to properly identify and treat children with headaches.

Methods: The Rare Disease Consortium Research Network for RTT is an NIH-funded project to characterize the clinical spectrum and natural history of RTT in advance of clinical trials. Evaluations include clinical status (classic vs atypical RTT), MECP2 mutations, clinical severity, and presence, frequency, and treatment of seizures.

Results: Enrollment as of June 2008 is 602; 528 (88%) meet clinical criteria for classic RTT. Of these, 493 (93%) have MECP2 mutations. Age range was 8 months to 64 years. A total of 360 (60%) were reported to have seizures, including 315 (60%) classic and 45 (61%) atypical RTT. Physician assessment of the 602 indicated that 48% had seizures. There was no significant difference in seizure occurrence by race/ethnicity. A significant age impact for seizures was seen and seizures were infrequent before age 2 years. MECP2 mutations most frequently associated with epilepsy were T158M (74%) and R106W (78%), and less frequently R255X and R306C (both 49%). Individuals with seizures had greater overall clinical severity, and greater impairment of ambulation, hand use, and communication.

Discussion: Seizures are common in Rett syndrome, have an age-related onset and occurrence, vary by mutation, and are associated with greater clinical severity. This information represents a key consideration for designing clinical trials.

Methods: We performed a case–control study of patients with AL amyloidosis with associated AN and compared them to a large matched cohort without AN who also underwent ASCT.

Results: We identified 13 patients with AN who underwent ASCT and a matched control group of 95 patients without AN. Patients with AN had more organs involved (median 2.5 vs 1, p < 0.001) and the conditioning dose of melphalan was often reduced by 30% compared to controls without AN (p = 0.0015). Median duration of hospitalization was similar for both cohorts, as were engraftment kinetics. Atrial fibrillation occurred in all patients with AN but in only 1 control patient (p < 0.0001). Median overall survival (OS) for patients with AN was 29 months but >60 months for controls (p < 0.0001). On univariate analysis, cardiac involvement (p = 0.0132), AN (p = 0.0011), glomerular filtration rate (p = 0.038), number of organs involved (p = 0.0064), and NT-pro-BNP (p = 0.039) all had an impact on OS. On multivariate analysis, AN retained an independent adverse impact on OS.

Conclusions: Patients with autonomic neuropathy secondary to AL amyloidosis can undergo autologous stem cell transplantation with relative safety. Autonomic neuropathy is an independent, adverse determinant of survival in these patients.

Methods: A literature search of MEDLINE, EMBASE, and Science Citation Index was performed to identify clinical trials in patients with nonmotor symptoms of PD published between 1966 and August 2008. Articles were classified according to a 4-tiered level of evidence scheme and recommendations were based on the level of evidence.

Results and Recommendations: Sildenafil citrate (50 mg) may be considered to treat erectile dysfunction in patients with Parkinson disease (PD) (Level C). Macrogol (polyethylene glycol) may be considered to treat constipation in patients with PD (Level C). The use of levodopa/carbidopa probably decreases the frequency of spontaneous nighttime leg movements, and should be considered to treat periodic limb movements of sleep in patients with PD (Level B). There is insufficient evidence to support or refute specific treatments for urinary incontinence, orthostatic hypotension, and anxiety (Level U). Future research should include concerted and interdisciplinary efforts toward finding treatments for nonmotor symptoms of PD.