Neurology August 2009 Volume 73 Issue 6

Objective: To assess the long-term outcome of a community-based adolescent cohort with chronic daily headache (CDH).Methods: A field sample of 122 adolescents aged 12-14 years with CDH was established in 2000 (baseline) with short-term follow-up studies in 2001 and 2002. In 2008, the cohort was re-interviewed by physicians via telephone to determine the headache profile for the past year, including Migraine Disability Assessment (MIDAS), a headache disability questionnaire. Presence of CDH was defined as >=15 headache days/month, average >=4 hours/day for >3 months. Outcome measures included headache frequency, MIDAS score, and presence of CDH in 2008.Results: A total of 103 subjects (26 male/77 female, mean age 21.6 +/- 0.9 years) completed the study (response rate 84.4%). The average monthly headache frequency was 4.7 +/- 6.0 (0-30) days. Twenty-eight (27.2%) subjects had moderate or severe headache disability (MIDAS >=11). Twelve (12%) subjects met CDH criteria, with chronic migraine (n = 10, 83%) as the most common subtype. Two (2%) subjects overused medications. From 2000 to 2008, the frequencies of migraine diagnoses were fairly consistent in this cohort. Presence of migraine at baseline predicted poorer outcome of all 3 measures. Additionally, CDH onset <13 years old, duration >=2 years, and medication overuse predicted either higher headache frequencies or presence of CDH in 2008.Conclusions: This long-term follow-up study revealed a marked decline in the frequency of chronic daily headache (CDH). However, one fourth of patients still had significant headache disability. Migraine history was a major factor in evolution of CDH into young adulthood. Early onset and longer duration of CDH implied a protracted disease course.(C)2009AAN Enterprises, Inc.

Objective: To describe the phenotype of adult patients with variant and classic ataxia-telangiectasia (A-T), to raise the degree of clinical suspicion for the diagnosis variant A-T, and to assess a genotype-phenotype relationship for mutations in the ATM gene.Methods: Retrospective analysis of the clinical characteristics and course of disease in 13 adult patients with variant A-T of 9 families and 6 unrelated adults with classic A-T and mutation analysis of the ATM gene and measurements of ATM protein expression and kinase activity.Results: Patients with variant A-T were only correctly diagnosed in adulthood. They often presented with extrapyramidal symptoms in childhood, whereas cerebellar ataxia appeared later. Four patients with variant A-T developed a malignancy. Patients with classic and variant A-T had elevated serum [alpha]-fetoprotein levels and chromosome 7/14 rearrangements. The mildest variant A-T phenotype was associated with missense mutations in the ATM gene that resulted in expression of some residual ATM protein with kinase activity. Two splicing mutations, c.331 + 5G>A and c.496 + 5G>A, caused a more severe variant A-T phenotype. The splicing mutation c.331 + 5G>A resulted in less ATM protein and kinase activity than the missense mutations.Conclusions: Ataxia-telangiectasia (A-T) should be considered in patients with unexplained extrapyramidal symptoms. Early diagnosis is important given the increased risk of malignancies and the higher risk for side effects of subsequent cancer treatment. Measurement of serum [alpha]-fetoprotein and chromosomal instability precipitates the correct diagnosis. There is a clear genotype-phenotype relation for A-T, since the severity of the phenotype depends on the amount of residual kinase activity as determined by the genotype.(C)2009AAN Enterprises, Inc.

Background: In gliomatosis cerebri (GC), defined as a diffuse neoplastic glial cell infiltration of the brain, upfront chemotherapy is often proposed as an alternative to radiotherapy. GC invades both white matter and gray matter in varying proportions, as reflected by the gray matter index (GMI), i.e., the estimated percentage of gray matter involvement.Methods: The GMI was estimated in 71 patients with GC (42 men and 29 women; median age, 47 years) treated with upfront chemotherapy (7 PCV, 64 temozolomide).Results: Median GMI was 30%. Patients were separated into 2 groups according to this median GMI. Compared to the 33 patients with GMI >30% (group B), the 38 patients from group A (defined as GMI <=30%) had better performance status (p = 0.03), higher response rate to chemotherapy (30/38 vs only 5/33; p < 0.0001), longer progression-free survival (21.2 vs 11.7 months, p = 0.005), and longer overall survival (56.1 vs 26.4 months; p = 0.003). There was no significant correlation with histologic subtype (oligodendroglial vs astrocytic or mixed GC), grading, tumor localization (particularly basal nuclei involvement), or laterality. The deletion of chromosomes 1p and 19q tended to be more frequent in group A (8/17 [47%] vs 1/9 [11%] in group B [p = 0.057]).Conclusion: These data suggest that gray matter index is a prognostic and predictive marker in gliomatosis cerebri that may in part depend on the 1p/19q status.(C)2009AAN Enterprises, Inc.

Objective: To evaluate the spatial pattern and regional rates of neocortical atrophy from normal aging to early Alzheimer disease (AD).Methods: Longitudinal MRI data were analyzed using high-throughput image analysis procedures for 472 individuals diagnosed as normal, mild cognitive impairment (MCI), or AD. Participants were divided into 4 groups based on Clinical Dementia Rating Sum of Boxes score (CDR-SB). Annual atrophy rates were derived by calculating percent cortical volume loss between baseline and 12-month scans. Repeated-measures analyses of covariance were used to evaluate group differences in atrophy rates across regions as a function of impairment. Planned comparisons were used to evaluate the change in atrophy rates across levels of disease severity.Results: In patients with MCI-CDR-SB 0.5-1, annual atrophy rates were greatest in medial temporal, middle and inferior lateral temporal, inferior parietal, and posterior cingulate. With increased impairment (MCI-CDR-SB 1.5-2.5), atrophy spread to parietal, frontal, and lateral occipital cortex, followed by anterior cingulate cortex. Analysis of regional trajectories revealed increasing rates of atrophy across all neocortical regions with clinical impairment. However, increases in atrophy rates were greater in early disease within medial temporal cortex, whereas increases in atrophy rates were greater at later stages in prefrontal, parietal, posterior temporal, parietal, and cingulate cortex.Conclusions: Atrophy is not uniform across regions, nor does it follow a linear trajectory. Knowledge of the spatial pattern and rate of decline across the spectrum from normal aging to Alzheimer disease can provide valuable information for detecting early disease and monitoring treatment effects at different stages of disease progression.(C)2009AAN Enterprises, Inc.

Vibration therapy is currently used in diverse medical specialties ranging from orthopedics to urology to sports medicine. The celebrated 19th-century neurologist, J.-M. Charcot, used vibratory therapy to treat Parkinson disease (PD). This study analyzed printed writings by Charcot and other writers on vibratory therapy and accessed unpublished notes from the Salpetriere Hospital, Paris. Charcot lectured on several occasions on vibratory therapy and its neurologic applications. He developed a vibration chair for patients with PD after he observed that patients were more comfortable and slept better after a train or carriage ride. He replicated this experience by having patients undergo daily 30-minute sessions in the automated vibratory chair (fauteuil trepidant). His junior colleague, Gilles de la Tourette, extended these observations and developed a helmet that vibrated the head on the premise that the brain responded directly to the pulsations. Although after Charcot's death vibratory therapy was not widely pursued, vibratory appliances are reemerging in 21st century medicine and can be retested using adaptations of Charcot's neurologic protocols.(C)2009AAN Enterprises, Inc.