Academy Continues to Push Congress on NIH and STOP Stroke Act

Background: Inferences about long-term effects of therapies in multiple sclerosis (MS) have been based on surrogate markers studied in short-term trials. Preventing progressive disability is the key therapeutic goal but there remains no validated definition for its measurement in a trial context. Meanwhile, MS trials continue to shorten and to depend on unvalidated surrogates. Since there have been no treatment claims for improving unremitting disability, worsening of disability in the placebo/control arm must occur for effectiveness on this outcome to be shown.Methods: We examined widely-used clinical surrogates of long-term disability progression in individual patients with MS within a unique database from the placebo arms of 31 randomized clinical trials.Results: Detection of treatment effects in secondary progressive MS trials is undermined by noise in disability measurement. Whereas existing measures can be partially validated in secondary progressive MS, this is not the case in relapsing-remitting MS. Here, examination of widely used definitions of treatment failure demonstrated that disability progression was no more likely than similarly defined improvement. Existing definitions of disease progression in short-term intervention trials in relapsing-remitting patients reflect random variation, measurement error, and remitting relapses.Conclusion: Clinical surrogates of unremitting disability used in trials of relapsing-remitting multiple sclerosis cannot be validated. Trials have been too short or degrees of disability change too small to measure the key outcomes. These analyses highlight the difficulty in determining effectiveness of therapy in chronic diseases.(C)2008AAN Enterprises, Inc.

Background: Chronic, excess zinc intake can result in copper deficiency and profound neurologic disease. However, when hyperzincemia is identified, the source often remains elusive. We identified four patients, one previously reported, with various neurologic abnormalities in the setting of hypocupremia and hyperzincemia. Each of these patients wore dentures and used very large amounts of denture cream chronically.Objective: To determine zinc concentration in the denture creams used by the patients as a possible source of excess zinc ingestion.Methods: Detailed clinical and laboratory data for each patient were compiled. Tubes of denture adhesives were analyzed for zinc content using dynamic reaction cell-inductively coupled plasma-mass spectrometry. Patients received copper supplementation. Copper and zinc levels were obtained post-treatment at varying intervals.Results: Zinc concentrations ranging from about 17,000 to 34,000 [mu]g/g were identified in Fixodent and Poli-Grip denture creams. Serum zinc levels improved in three patients following cessation of denture cream use. Copper supplementation resulted in mild neurologic improvement in two patients who stopped using denture cream. No alternative source of excess zinc ingestion or explanation for hypocupremia was identified.Conclusion: Denture cream contains zinc, and chronic excessive use may result in hypocupremia and serious neurologic disease.(C)2008AAN Enterprises, Inc.

Imaging for headaches is one of the most frequent and at times challenging decisions a neurologist has to make in the clinical practice of neurology and is complicated by today's medical-legal milieu and overseeing regulatory organizations. Although the final decision should always be made by the treating physician, the American Academy of Neurology has developed practice parameters for the imaging of headaches. One strong criticism of the overzealous use of neuroimaging in patients with headache is the frequency of incidental findings, which may in turn increase a patient's anxiety and potentially cause an exacerbation of symptoms. This may subsequently lead to unnecessary testing as well as neurosurgical intervention. The clinical interpretation of incidental findings and headaches is best made by a neurologist who is able to correlate the imaging findings with the patient's symptoms and examination. One of the principal precepts in medicine, "primum nil nocere" or "first, do no harm" to patients, should be considered in the interpretation of these so-called abnormalities. The development of programs to certify competence in physicians who have completed accredited training programs in neuroimaging as well as headache medicine by the United Council for Neurologic Subspecialties is an important advancement that allows clinicians the opportunity to enhance quality of patient care.(C) 2008 American Academy of Neurology

Structural brain imaging with CT or MRI should be performed in any patient with progressive cognitive impairment to rule out a reversible cause, such as a benign brain tumor, a subdural hematoma, or hydrocephalus. But imaging can also help separate the various types of degenerative dementia and facilitates the prognosis of these disorders. Medial temporal atrophy is an early finding in Alzheimer disease (AD). Early in AD, metabolism is decreased in the parietotemporal association cortex and retrosplenial region. When these imaging findings are present in mild cognitive impairment, it is more likely to evolve to AD. Amyloid deposition in AD and Lewy body dementia can now be imaged, differentiating these disorders from dementias without amyloid deposition, such as frontotemporal dementia and corticobasal degeneration. Atrophy or the decrease in brain metabolic activity associated with the dementias could be used as surrogate markers of response to new therapies in clinical trials.(C) 2008 American Academy of Neurology