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Pirko et al. found that gray matter (GM) involvement is detected even in the earliest stages of MS and GM atrophy occurs at a faster rate than WM atrophy early in the disease course. Studies published to date establish that 1) GM involvement and in particular cortical demyelination can be extensive in MS; 2) GM pathology may occur in part independent of WM lesion formation; 3) a primarily GM-related process may be the earliest manifestation of MS; 4) GM involvement is associated with physical disability, fatigue, and cognitive impairment in MS; and 5) GM disease might help explain the observed dissociation between markers of inflammatory demyelination (relapses, WM gadolinium enhancement, WM lesion burden) and disease progression. It remains likely that GM damage is related to WM damage. However, continued studies of GM pathology, as well as neuronal and axonal involvement in MS and related experimental models, are necessary in order to better understand the etiology and pathogenesis of the degenerative components.
see page 634
See the Patient Page at www.neurology.org.
Age, expertise independently predict pilot performance
Taylor et al. tested 118 pilots aged 40 to 69 years annually in a flight simulator to address aging workforce issues. Compared to younger pilots, older pilots initially performed worse, yet they did not show steeper declines. Highly trained pilots showed remarkably stable performance over time.
see page 648
The editorial by Sirven and Morrow notes that recently, the International Civil Aviation Organization, which sets world aviation standards, implemented a policy change. Because it could not find evidence that pilots in their 60s were more prone to mistakes than younger pilots, they issued a change in retirement age to 65 years. With this change, only the United States, France, Pakistan, and Columbia will maintain the age 60 retirement rule. They also note that the findings from Taylor et al. have an applicability that extends well beyond to the general issue of aging in the workplace. They argue that it is now time to reconsider fixed age limits for the workplace and consider transitioning to competency-based evaluations of performance. Better simulation techniques need to be developed not only in aviation, but also in medicine and other careers where public safety is at risk.
see page 630
MRI and serial 18FDG-PET in childhood partial epilepsy
Thirty-eight children had serial 18FDG-PET scans over 3 years after partial epilepsy onset. Gaillard et al. found no evidence for progression of PET hypometabolism. Consistently abnormal PET was associated with poor seizure control. A model combining MRI and initial PET was strongly predictive of clinical course.
see page 655
Serum lipid profiles in stroke and TIA
On admission, Smith et al. determined that 27% of patients with stroke/TIA have serum LDL levels above recommended guidelines. The data suggest that serum lipids should be measured in all patients with stroke/TIA, even those with known dyslipidemia or who were already on lipid-lowering agents prior to the index stroke/TI.
see page 660
CSF Ab: Biomarker for AD doubles in hours
CSF Ab is a specific biomarker of amyloid deposition in the brain and may be useful as a predictive test for AD. Bateman et al. studied hourly Ab levels in human CSF and found levels fluctuated by 200% or more within a few hours. The dynamic nature of these changes suggests CSF Ab may be influenced by neuronal activity.
see page 666
Serum 
-tocopherol and mild cognitive impairment
In a cross-sectional analysis of 525 women age 60+, Dunn et al. found lowest quartile of serum -tocopherol to be associated with nearly twofold increased odds of memory and mixed-domain mild cognitive impairment, when adjusting for age, education, and reading ability.
see page 670
Muscles and nerves in familial partial lipodystrophy (FPLD)
Muscle hypertrophy, pain, and nerve entrapments were prominent clinical findings in patients with FPLD. Myostatin mRNA expression was reduced while SMAD molecules adhered to the nuclear membrane from FPLD myocytes. Spuler et al. hypothesize that in FPLD, LMNA mutations interfere with SMAD nuclear trafficking, rendering myostatin signaling ineffective.
see page 677
APP promoter revisited
The recent discovery that APP locus duplication causes AD and cerebral amyloid angiopathy strengthens the hypothesis that DNA polymorphisms affecting gene expression might confer risk to AD. Guyant-Maréchal et al. describe an association between a polymorphism in the promoter region of the APP gene and AD.
see page 684
The editorial by Hardy and Myers notes that while Guyant-Maréchal et al. demonstrate that common genetic variability near the proximal promoter of the APP gene may contribute to the risk of AD in their sample French population, their study does not address whether further common genetic variability elsewhere at the APP locus also contributes to disease risk or whether rare genetic variability contributes more substantively to the risk of disease in specific families.
see page 632
Priming and the occipital cortex of the blind
Kupers et al. applied rTMS over the occipital cortex in the blind. After rTMS, participants made more errors and showed reduced reading speed improvement following repetitive presentation of the same Braille list, suggesting a role of the visual cortex in repetition priming.
see page 691
CT and MRI select the same stroke patients for acute treatment
PCT/CTA and MRI perform similarly in characterizing infarct size, cortical involvement, penumbra/infarct ratio, and ICA occlusion in a series of 42 patients with stroke. Wintermark et al. found that relying on MRI or PCT/CTA would have led to the same treatment decisions in all but one case.
see page 694
Long-term temozolomide is safe in high-grade gliomas
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Hau et al. surveyed neuro-oncologists regarding patients treated with temozolomide for at least 12 cycles or 12 months. Patients receiving first-line temozolomide for a median 13 cycles had a median progression-free survival of 14 months. Patients with recurrent disease receiving a median 14 cycles had a median progression-free survival of 15.5 months. A small percentage of patients experienced grade 3/4 toxicity. These results suggest that long-term treatment with temozolomide is feasible and well tolerated.
see page 688
A clinical case with surprising genetics
Well-established clinical classifications are being challenged by progress in molecular genetics. Horn et al. describes the phenotype of a patient with adult Refsum disease, who carries a gene defect that should have predicted rhizomelic chondrodysplasia punctata type-1, an altogether different clinical disorder.
see page 698
Related articles in Neurology:
-tocopherol, concurrent and past vitamin E intake, and mild cognitive impairment
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