From the publishers of The New England Journal of Medicine July 2008 Vol. 10 No. 7 Amyloid Plaques Are reinforce the notion that amyloid plaques the 40-odor University of Pennsylvania are dynamic, again suggesting that Smell Identification Test (UPSIT) and Surprisingly Dynamic they do not result from an unstoppable an average of 2.9 years later (range, 3 he amyloid hypothesis of Alzheimer march of amyloid accretion but, rather, months to 24 years) with the 40-odor T disease predicts that amyloid plaques from a process wherein plaques may UPSIT or a 12-odor version. (One of the are a precursor of neuronal damage. come and (with manipulation) go. Un- study authors is a shareholder in the However, researchers recently proposed doubtedly, the kinetics are different in company that manufactures the smell that neuronal damage may precede humans, but again, overturning conven- test used.) plaque formation. In this study, the tional wisdom enables the contemplation From baseline to follow-up, 11.3% of authors used a novel imaging technique of therapeutic opportunities that might anosmic and 23.3% of hyposmic patients to provide insights into the chronology heretofore have been discarded out regained their age-adjusted sense of of amyloid deposition in the brains of of hand. smell (although significant improvement transgenic mice bred to overexpress — Sam Gandy, MD, PhD occurred in 56.7% and 42.7%, respec- human amyloid precursor protein. Meyer-Luehmann M et al. Rapid appear- tively). Age, initial severity of smell loss, The authors monitored brain paren- ance and local toxicity of amyloid-β and time from onset to baseline signifi- chyma of these transgenic mice weekly plaques in a mouse model of Alzheimer’s cantly predicted the degree of recovery; disease. Nature 2008 Feb 7; 451:720. and then daily. They observed that fully the cause of initial impairment, elapsed morphologically typical amyloid plaques time between tests, gender, and initial could appear within a single day, and smoking habit did not. The authors em- develop to their final size within 1 week. Predicting Recovery phasize the value of quantitative assess- Evidence of neuritic dystrophy appeared ment of smell loss, as 87 of the study after the plaques appeared. from Smell Loss participants had no smell loss on testing. Comment: his was a longitudinal study of pre- Comment: dictors of recovery in 542 people The development of methods for visual- T Smell identification was undertaken who complained of smell loss due to izing amyloid plaques in vivo has led to by two different methods. The authors various causes, including trauma, infec- ongoing revision of our understanding acknowledge the possibility, but con- tion, surgery, and medical treatments. of the biology of these structures. The sider it unlikely, that the loss of sensitiv- Testing was conducted at baseline (mean first surprise, from 3 years ago, was that ity inherent in comparing the two time since smell loss, 1.08 years) with antibodies against amyloid-β could clear away both deposits and the accompany- ing neuritic dystrophy in mice (Nat Med TABLE OF CONTENTS 2001; 7:369). This was quite unexpected, because experimental solubilization of Amyloid Plaques Are New Brain Tumor Therapies, deposits has required denaturing con- Surprisingly Dynamic ........................49 New Recurrence Patterns ................. 53 centrations of guanidine. The relevance Predicting Recovery from Smell Loss .... 49 SOX1 Antibodies and Paraneoplastic Lambert-Eaton of rapid plaque turnover in mice to Does the Vitamin D Emperor Have Clothes? ..................... 50 Myasthenic Syndrome ....................... 53 what is certainly a slower process in Cortical Demyelination in MS Distinguishing Polymyositis humans remains unclear. But upending and Progressive Multifocal from Inclusion Body Myositis ............54 the conventional wisdom led many in Leukoencephalopathy ........................51 Restless Legs Syndrome Is Associated the field to contemplate amyloid clear- Epilepsy and Mental Retardation with Cardiovascular Disease .............54 ance as a serious therapeutic possibility. in Females: Unusual Inheritance ........51 Diaphragm Shrinkage in Mechanically The current findings indicate that Effects of Vagus Nerve Stimulation Ventilated Patients .............................55 plaque deposition can occur just as on Cardiovascular Regulation ........... 52 Predicting Outcome in Vestibular Neuritis ......................... 55 rapidly as can plaque clearance. This Platelet Aggregometry as a Marker of Risk for Vascular Events: Not Yet ......52 Surgery Beneficial study has become an instant classic, Venous Sinus Stenting for Idiopathic for Lumbar Spinal Stenosis ................56 nicknamed the “popcorn plaque” paper Intracranial Hypertension .................52 among the cognoscenti. The findings Journal Watch (and its design) is a registered trademark of the Massachusetts Medical Society. An editorially independent literature-surveillance newsletter summarizing articles from major medical journals. ©2008 Massachusetts Medical Society. All rights reserved. Disclosure information about our authors can be found at http://neurology.jwatch.org/misc/board_disclosures.dtl Page 50 JOURNAL WATCH NEUROLOGY Volume 10 Number 7 EDITOR-IN-CHIEF different procedures weakens the over- other clinical chemistry assays in the Martin A. Samuels, MD, FAAN, MACP, DSc (hon) all conclusion; if so, the 12-odor test 23 patients with MS and in 23 healthy Professor of Neurology, Harvard Medical School; should have been used on both occasions. laboratory workers (controls). Neurologist-in-Chief and Chairman, Department of Neurology, Although the analysis suggests that The authors state that half of all par- Brigham and Women’s Hospital, Boston original etiology is unimportant, there ticipants had S-25(OH)D levels at or were just two major initial causes (upper below 37 nmol/L (considered deficient) DEPUTY EDITOR respiratory infection and head trauma). at some point during the year. Levels Galen V. Henderson, MD Neurologist, Division of Cerebrovascular Diseases, Idiopathic cases would be difficult to of 25(OH)D were lower and levels of Department of Neurology, include in an etiology-based analysis. intact parathyroid hormone (iPTH) were Brigham and Women’s Hospital, Boston The findings are still useful, but arguably higher during relapses than during re- EXECUTIVE EDITOR they cannot be applied to all cases of missions. The abstract also states, “All Christine Sadlowski smell loss. Intuitively, it would be re- 21 relapses during the study occurred Massachusetts Medical Society markable if all causes of anosmia had at serum iPTH levels >20 ng/L. where- ADVISORY BOARD the same outlook when matched for as 38% of patients in remission had Clive Hawkins, MD, DM initial severity. Given that improvements iPTH levels ≤20 ng/L. There is an in- Professor of Clinical Neurology, Keele University Medical School; University Hospital of North in smell can occur in as little as 3 months, verse relationship between serum vita- Staffordshire, Stoke-on-Trent, United Kingdom the long intervals between the initial min D level and MS clinical activity.” smell loss and baseline for most study Bryan M. Kies, MD Comment: Associate Professor, Neurology Division, Faculty of participants might explain the apparent Health Sciences, University of Cape Town; Senior prognostic similarity for the different This simple clinician had some difficulty Specialist, Groote Schuur Hospital, Cape Town, following the authors’ presentation. The South Africa etiologies. The patients who improved after baseline might have been those who supplementary figure published online Jun Kimura, MD plotted vitamin D levels and relapses Professor, Emeritus, Kyoto University, Kyoto, were tested earlier in their condition’s Japan; Professor, Department of Neurology, evolution than those who fared badly. over a 1-year interval for 12 patients. Iowa University Health Care, Iowa City, IA This is the largest study of smell re- Relapses did not occur any more often Edward H. Koo, MD covery so far and provides guidance during the presumed high-risk months Professor, Department of Neurosciences, (8 in December through May, when University of California at San Diego, La Jolla, CA in a hitherto poorly defined area. The findings are clearly valuable in counsel- vitamin D levels are lowest) than during Alberto Portera-Sanchez, MD the other months (11 relapses). Professor of Neurology, Emeritus, ing patients and plaintiffs in lawsuits. Complutense University, Madrid, Spain They counter the widely held belief that Figure 2 of the article is a scatter plot of S-25(OH)D and iPTH levels from Amy A. Pruitt, MD olfactory loss is largely irreversible and Department of Neurology, University of are consistent with the theory that origi- patient specimens drawn during relapse Pennsylvania Medical Center, Philadelphia nal cause determines outlook. These (21) or remission (122). All values for Thomas D. Sabin, MD results are of value in assessing olfactory the relapses fit well within calculable Professor and Vice Chair, confidence intervals for the remission Department of Neurology, Tufts University disturbance due to trauma and infection. School of Medicine, Boston I suspect the prognosis estimate will values: Mean vitamin D levels and standard deviations (SDs) were Thomas R. Swift, MD be less accurate for anosmia related to Professor and former Chair, Department of Neurology, neurosurgical and neurodegenerative 47.4±14.4 nmol/L