Neurology January 2009 Volume 72 Issue 4

Objective: To compare the characteristics of idiopathic intracranial hypertension (IIH) in men vs women in a multicenter study.Methods: Medical records of all consecutive patients with definite IIH seen at three university hospitals were reviewed. Demographics, associated factors, and visual function at presentation and follow-up were collected. Patients were divided into two groups based on sex for statistical comparisons.Results: We included 721 consecutive patients, including 66 men (9%) and 655 women (91%). Men were more likely to have sleep apnea (24% vs 4%, p < 0.001) and were older (37 vs 28 years, p = 0.02). As their first symptom of IIH, men were less likely to report headache (55% vs 75%, p < 0.001) but more likely to report visual disturbances (35% vs 20%, p = 0.005). Men continued to have less headache (79% vs 89%, p = 0.01) at initial neuro-ophthalmologic assessment. Visual acuity and visual fields at presentation and last follow-up were significantly worse among men. The relative risk of severe visual loss for men compared with women was 2.1 (95% CI 1.4-3.3, p = 0.002) for at least one eye and 2.1 (95% CI 1.1-3.7, p = 0.03) for both eyes. Logistic regression supported sex as an independent risk factor for severe visual loss.Conclusion: Men with idiopathic intracranial hypertension (IIH) are twice as likely as women to develop severe visual loss. Men and women have different symptom profiles, which could represent differences in symptom expression or symptom thresholds between the sexes. Men with IIH likely need to be followed more closely regarding visual function because they may not reliably experience or report other symptoms of increased intracranial pressure.(C)2009AAN Enterprises, Inc.

Objective: We examined the effect of aerobic exercise in patients with spinal and bulbar muscular atrophy (SBMA). SBMA is caused by a defect androgen receptor. This defect causes motor neuron death, but considering the important function of androgens in muscle, it is possible that muscle damage in SBMA also occurs independently of motor neuron damage.Methods: Eight patients with SBMA engaged in regular cycling exercise for 12 weeks. Maximum oxygen uptake (Vo2max), maximal work capacity (Wmax), muscle morphology, citrate synthase (CS) activity, body composition, EMG, static strength measurements, lung function, plasma proteins, and hormones were evaluated before and after training. Evaluation of improvements in activities of daily living (ADL) was conducted after training.Results: Wmax increased by 18%, and CS activity increased by 35%. There was no significant change in Vo2max or any of the other variables examined before and after training, and the patients with SBMA did not feel improvements in ADL.Conclusions: Frequent, moderate-intensity aerobic conditioning is of little beneficial effect in patients with spinal and bulbar muscular atrophy (SBMA). High levels of plasma creatine kinase and muscle regeneration indicate a primary myopathic affection, which, in parallel with the motor neuron deficiency, may attenuate the response to exercise training in patients with SBMA.(C)2009AAN Enterprises, Inc.

Background: Functional single nucleotide polymorphisms (SNP) in codon 72 of TP53 have been shown to be a risk factor, a prognostic marker, and related factor to age at onset in various cancers.Methods: We investigated blood samples from 254 patients with glioblastoma and 238 healthy controls.Results: TP53 codon 72 status was not correlated with prognosis and did not differ between glioblastoma and control populations. However, the Pro/Pro genotype was overrepresented in patients <45 years (20.6% vs 6.4% in patients with glioblastoma >45 years, p = 0.002, vs 5.9% in control group, p = 0.001). We then confirmed this result on an independent series of young patients with glioblastoma. Finally, the analysis of tumor DNA found the Pro allele associated with occurrence of TP53 somatic mutation.Conclusion: Our data suggest that TP53 functional variation is particularly critical for oncogenesis of glioblastoma in young patients.(C)2009AAN Enterprises, Inc.

Background: Cluster headache is a primary headache involving repeated attacks of excruciatingly severe headache usually occurring several times a day. Most patients with chronic cluster headache (CCH) have an unremitting illness requiring daily preventive therapy for years.Objective: To describe the clinical outcome of occipital nerve stimulation (ONS) for 14 patients with intractable CCH.Methods: Fourteen patients with medically intractable CCH were implanted with bilateral electrodes in the suboccipital region for ONS and a retrospective assessment of their clinical outcome obtained.Results: At a median follow-up of 17.5 months (range 4-35 months), 10 of 14 patients reported improvement and 9 of these recommend ONS. Three patients noticed a marked improvement of 90% or better (90%, 90%, and 95%), 3 a moderate improvement of 40% or better (40%, 50%, and 60%), and 4 a mild improvement of 20-30% (20%, 20%, 25%, and 30%). Improvement occurred within days to weeks for those who responded most and patients consistently reported their attacks returned within hours to days when the device was off. One patient found that ONS helped abort acute attacks. Adverse events of concern were lead migrations and battery depletion.Conclusion: Intractable chronic cluster headache (CCH) is a devastating, disabling condition that has traditionally been treated with cranially invasive or neurally destructive procedures. ONS offers a safe, effective option for some patients with CCH. More work is required to evaluate and understand this novel therapy.GLOSSARY: CCH = chronic cluster headache; DBS = deep brain stimulation; DHE = dihydroergotamine; ONS = occipital nerve stimulation.(C)2009AAN Enterprises, Inc.

Background: Autopsy series have shown that some elderly people remain with normal cognitive function during life despite having high burdens of pathologic lesions associated with Alzheimer disease (AD) at death. Understanding why these individuals show no cognitive decline, despite high AD pathologic burdens, may be key to discovery of neuroprotective mechanisms.Methods: A total of 36 subjects who on autopsy had Braak stage V or VI and moderate or frequent neuritic plaque scores based on Consortium to Establish a Registry for Alzheimer's Disease (CERAD) standards were included. Twelve had normal cognitive function and 24 a diagnosis of AD before death. Demographic characteristics, clinical and pathologic data, as well as antemortem brain volumes were compared between the groups.Results: In multiple regression analysis, antemortem hippocampal and total brain volumes were significantly larger in the group with normal cognitive function after adjusting for gender, age at MRI, time from MRI to death, Braak stage, CERAD neuritic plaque score, and overall presence of vascular disease.Conclusion: Larger brain and hippocampal volumes were associated with preserved cognitive function during life despite a high burden of Alzheimer disease (AD) pathologic lesions at death. A better understanding of processes that lead to preservation of brain volume may provide important clues for the discovery of mechanisms that protect the elderly from AD.GLOSSARY: AD = Alzheimer disease; CDR = Clinical Dementia Rating Scale; CERAD = Consortium to Establish a Registry for Alzheimer's Disease; CIRS = Cumulative Illness Rating Scale; ICV = intracranial volume; LB = Lewy bodies; MMSE = Mini-Mental State Examination; NCSE = Neurobehavioral Cognitive Status Examination; NFT = neurofibrillary tangle; NIA = National Institute on Aging; NP = neuritic plaques; OHSU = Oregon Health & Science University; Ref = reference; SES = socioeconomic status; UPDRS = Unified Parkinson's Disease Rating Scale.(C)2009AAN Enterprises, Inc.

In recent years, accumulating evidence has suggested that vascular risk factors contribute to Alzheimer disease (AD). Vascular dementia had been traditionally considered secondary to stroke and vascular disease. It has been traditionally distinguished from AD, considered to be a purely neurodegenerative form of dementia. However, in light of this more recent literature, it appears that there is a spectrum: ranging from patients with pure vascular dementia to patients with pure AD and including a large majority of patients with contributions from both Alzheimer and vascular pathologies. In this article, we discuss the impact of vascular risk factors on AD and its consequences at the individual level and at the population level by highlighting the concept of attributable risk. We then discuss the key questions and next steps involved in designing a therapeutic trial to control vascular risk factors for the prevention of dementia.(C)2009AAN Enterprises, Inc.

Objective: To survey adult neurology program directors (ANPD) to identify their most pressing needs at a time of dramatic change in neurology resident education.Methods: All US ANPD were surveyed in 2007 using an instrument adjusted from a 1999 survey instrument. The goal was to characterize current program content, the institution and evaluation of the core competencies, program director characteristics, program director support, the institution of work duty hour requirements, resident support, and the curriculum needs of program directors and programs.Results: A response rate of 82.9% was obtained. There is a significant disconnect between administration time spent by ANPD and departmental/institutional support of this, with ANPD spending approximately 35% of a 50-hour week on administration with only 16.7% salary support. Rearrangement of rotations or services has been the most common mode for ANPD to deal with work duty hour requirements, with few programs employing mid level providers. Most ANPD do not feel work duty hour reform has improved resident education. More residents are entering fellowships following graduation than documented in the past. Curriculum deficiencies still exist for ANPD to meet all Neurology Program Requirements, especially for nontraditional neurology topics outside the conventional bounds of clinical neurology (e.g., practice management). Nearly one quarter of neurology residency programs do not have a meeting or book fund for every resident in the program.Conclusions: Adult neurology program directors (ANPDs) face multiple important financial and organizational hurdles. At a time of increasing complexity in medical education, ANPDs need more institutional support.(C)2009AAN Enterprises, Inc.