The following research from NewYork-Presbyterian Hospital/ Columbia University Medical Center is being presented at the 64th annual meeting of the American Academy of Neurology (AAN), April 21-26, 2012, in New Orleans.
Dynamic Cerebral Autoregulation Is Transiently Impaired after Large-Vessel Acute Ischemic Stroke
Authors: Nils Petersen, Santiago Ortega-Gutierrez, Andres Reccius, Amy Huang, Arjun Masurkar, and Randolph Marshall
Background/Significance: Dynamic cerebral autoregulation (DCA) is the continuous early counter-regulation of cerebral blood vessels in response to changes in systemic blood pressure. DCA can become impaired after acute stroke, but it is unclear to what extent or how the impairment progresses over time. Data from this study suggest that DCA is impaired in the brain's affected hemisphere in the first week after large-vessel ischemic stroke and then normalizes by week two. These findings may have important implications for acute blood pressure management after stroke.
Session Information: S19.002, Ischemic Cerebrovascular Disease and Subarachnoid
Presentation Time: Tuesday, April 24, 3:15 pm
Increased Regional Expression of Lingo-1 in the Essential Tremor Cerebellum: A Postmortem, Case-Control Study
Authors: Sheng-Han Kuo, Guomei Tang, Karen Ma, Rachel Babij, Ai Yamamoto, Jean-Paul G Vonsattel, Phyllis L Faust, David Sulzer, and Elan D Louis
Background/Significance: A sequence variant (rs9652490) in the Lingo-1 gene has been associated with essential tremor (ET) in an initial genome-wide association study and several follow-up studies. However, how Lingo-1 contributes to the development of ET is not well understood. In this study, researchers show that Lingo-1 expression seems to be increased in the ET cerebellum, but not in the ET occipital cortex. A higher expression of Lingo-1 protein in ET could contribute to the abnormal PC axonal pathology that has been observed in this disorder.
Session Information: S32.003, Hyperkinetic Disorders: Essential Tremor, Tourette's Syndrome, and Huntington's Disease
Presentation Time: Wednesday, April 25, 4:30 pm
Clinical and Genetic Characteristics of Participants with Juvenile PD: the CORE-PD study
Authors: Roy Alcalay, Llency Rosado, Helen Mejia-Santana, Martha Orbe-Reilly, Elise Caccappolo, Mingxin Tang, Diana Ruiz, Barbara Ross, Miguel Verbitsky, Sergey Kisselev, Elan Louis, Cynthia Comella, Amy Colcher, Danna Jennings, Martha Nance, Susan Bressman, William Scott, Caroline Tanner, Howard Andrews, Cheryl Waters, Stanley Fahn, Lucien Cote, Steven Frucht , Blair Ford, Michael Rezak, Kevin Novak, Joseph Friedman, Ronald Pfeiffer, Laura Marsh, Bradley Hiner, Andrew Siderowf, Haydeh Payami, Eric Molho, John Nutt, Stewart Factor, Ruth Ottman, Lorraine Clark, and Karen Marder
Background/Significance: Parkinson disease (PD) is largely a disease of the elderly, although it can begin before age 50 (early-onset PD) and in very rare cases before age 21 (juvenile PD). In this multicenter study, possibly the largest of its kind, researchers analyzed the clinical and genetic characteristics of 20 patients with juvenile PD. Among the findings were that patients with juvenile PD fare quite well despite long disease duration and that the disease progresses more slowly when it begins at a younger age. Several genetic mutations that had been previously linked to PD were identified in these patients, most commonly a gene called PRKN. The ongoing study will help identify new risk factors for juvenile PD. It will also help researchers gain a better understanding of PD in general, by distinguishing those symptoms that are related to the disease from those that are related to aging.
Session Information: S42.002, Epidemiology of Parkinson's Disease
Presentation Time: Thursday, April 26, 1:15 pm
New MPV17 Mutations Associated with Multiple Deletions in Skeletal Muscle
Authors: Caterina Garone, Juan Carlos Rubio, Sarah E. Calvo, Ali Naini, Kurenai Tanji, Salvatore DiMauro, Vamsi K. Mootha, and Michio Hirano
Background/Significance: Mitochondrial DNA (mtDNA) depletion syndrome is defined by significant reduction of mtDNA in affected tissues, which can lead to respiratory chain complex deficiencies and severe childhood (hepato) encephalomyopathies. In this study, next-generation exome sequencing, along with a mitochondrial gene library, was applied to identify new mtDNA mutations in an adult with motor neuropathy, ptosis (eyelid drooping), diabetes, and exercise intolerance, among other symptoms. The mutations were found to involve the MPV17 gene, which codes for an inner mitochondrial membrane protein. The findings confirm the researchers' previous hypothesis that MPV17 plays a role in mtDNA maintenance and broadens the clinical spectrum of MPV17 mutations to include adult, as well as neonatal, onset.
Session Information: S55.002, Muscle Disorders
Presentation Time: Thursday, April 26, 3:15 pm
Congenital Megaconial Myopathy Due to a Novel Defect in the Choline Kinase beta (CHKB) Gene
Background/Significance: Mutations in the choline kinase beta (CHKB) gene have been described in 15 children with congenital muscular dystrophy and mental retardation. The morphologic hallmark was the presence in muscle of giant mitochondria displaced to the periphery of the fibers. This study describes the first American patient with CHKB mutations, confirming the phenotype (clinical presentation) of CHKB mutations. Further, the researchers propose that this disorder affects the mitochondria-associated membrane (MAM) and that impaired phospholipid metabolism in MAM causes both the abnormal size and the displacement of muscle mitochondria.
Authors: Purificacion Gutierrez Rios, Arun Asha Kalra, Jon Wilson, Kurenai Tanji, H. Akman, Estela Area, Eric Schon, and Salvatore DiMauro
Session Information: P01.116, Neurologic Manifestations of Systemic Disease: Clinical
Presentation Time:, Monday, April 23, 2:00-6:30 pm
Comparison between Institutionally-Defined Clinical Criteria and CDC-Criteria for the Diagnosis of Ventriculostomy-Related Infection
Background/Significance: Diagnosis of infections related to ventriculostomy (a neurosurgical procedure that involves creating a hole within a cerebral ventricle for drainage) is commonly based on clinical impressions rather than specific criteria, often resulting in misdiagnoses and overuse of antibiotics. In this study, most patients diagnosed with ventriculostomy-related infection (VRI) did not meet criteria established by the Centers for Disease Control and Prevention. According to the researchers, improved clinical parameters for defining VRI must be developed for more precise patient management.
Authors: Barry Czeisler, H. Alex Choi, KuangHa Guo, Paul Bernstein, Mary Presciutti, Hector Lantigua, Amanda Carpenter, John Zhang, Sang-Bae Ko, J. Michael Schmidt, Jan Claassen, Stephan Mayer, Kiwon Lee, E. Sander Connolly, and Neeraj Badjatia
Session Information: P02.220, Subarachnoid Hemorrhage and Intracerebral Hemorrhage
Presentation Time: Tuesday, April 24, 7:30 am-12 pm
Falls and Spinal Muscular Atrophy (SMA): Exploring Cause and Prevention
Background/Significance: Falls can lead to injury and compromise function of patients with neuromuscular disorders. Weakness is an obvious contributing factor. Gait variability is associated with falls in other neurological disorders and may be associated with falls in patients with spinal muscular atrophy (SMA). Fatigue has been well documented in SMA, but an association between fatigue and falls has never been investigated. In this study, stride-length variability was associated with falls in SMA and may be related to selective weakness in hip flexor and knee extensor muscles. Future studies with larger samples are planned to examine the causal relationship between gait disturbances and falls. These studies anticipate rehabilitative interventions targeting factors that put this vulnerable population at risk for injury-causing falls.
Authors: Jacqueline Montes, Tara McIsaac, Sally Dunaway, Shirit Kamil-Rosenberg, Douglas Sproule, Carol Garber, Darryl De Vivo, and Ashwini Rao
Session Information: P03.177, Anterior Horn: Spinal Muscular Atrophy and TDP43
Presentation Time: Tuesday, April 24, 2:00-6:30 pm
Screen Failures in an Idiopathic Neuropathy Pain Clinical Trial
Background/Significance: Researchers evaluated the reason why patients were excluded from a clinical trial of a medication for painful idiopathic (of unknown cause) peripheral neuropathy. A major reason for exclusion was that patients were taking a similar medication or other medications that, if combined with the medication under study, could result in serious side effects. Other patients were excluded because their disease was found to have a specific cause; i.e., it was not idiopathic. These findings could help in designing future studies in terms of inclusion/exclusion criteria.
Authors: Khosro Farhad, Stacy-Ann Mano, and Thomas Brannagan
Session Information: P03.206, Peripheral Nerve: Small Fiber and Pain
Presentation Time: Tuesday, April 24, 2:00-6:30 pm
Severe Infantile Encephaloneuromyopathy and Defective Mitochondrial Translation Due to a New Molecular Defect
Background/Significance: Little is known about the mechanisms involved in the synthesis of mitochondrial proteins. Defects in this process can lead to metabolic disorders, which are common and mostly untreatable. In this study, researchers identified a genetic mutation that is responsible for a new disease phenotype (clinical presentation) associated with impaired mitochondrial protein synthesis. Overexpression of the wild-type (normal) protein normalizes levels of mitochondrial respiratory chain proteins. These finding will help elucidate the mechanisms that regulate mitochondrial protein synthesis and contribute to the development of rational therapeutic approaches for mitochondria-related disease.
Authors: Catarina M. Quinzii, Mario H. Barros, Simone Sanna-Cherchi, Valentina Emmanuele, Beatriz Lopez Garcia, Asan O. Akman, Rita Horvath, Claudia Ferreiro-Barros, Nader El Gharably, Darryl De Vivo, Aly Shokr, and Michio Hirano
Session Information: IN7-1.003, Poster Rounds, Integrated Neuroscience Session: Mitochondrial Diseases in Neurology
Presentation Time: Tuesday, April 24, 3:00-4:00 pm
Increased Prevalence of Migraine in Patients with Celiac Disease and Inflammatory Bowel Disease Compared to Controls: A Multicenter Prospective Study
Background/Significance: In this study, the first of its kind in the U.S., migraine headaches were found to be common in patients with celiac disease. Such headaches may be the most common neurologic manifestation of gluten intolerance. Future studies are needed to screen migraine patients for gluten sensitivity/celiac disease, particularly those with treatment-resistant headaches, as well as to assess the long-term effect of a gluten-free diet on migraine headache.
Authors: Alexandra Dimitrova, Ryan Ungaro, Benjamin Lebwohl, Mark Green, Mark Babyatsky, and Peter Green
Session Information: P04.237, Headache II
Presentation Time: Wednesday, April 25, 7:30 am-12 pm
MitoExome Sequencing Reveals a Mutation in the Mitochondrial MRPL51 Gene Causing Infantile Encephalopathy
Background/Significance: This study describes a new genetic mutation associated with infantile encephalopathy. The mutation involves the MRPL51 gene, which encodes a large mitochondrial ribosomal protein. Mutations to this gene lead to impaired mitochondrial respiratory enzyme activities in muscle, brain, and liver. The study also demonstrated the accuracy of MitoExome sequencing in identifying molecular causes of infantile mitochondrial disorders. MitoExome sequencing uses new technologies known as next-generation sequencing to decode all of the mitochondrial genes in patients, which helps pinpoint genetic abnormalities that cause disease.
Authors: Caterina Garone, Sarah Calvo, Valentina Emmanuele, H. Orhan Akman, Paige Kaplan, Sindu Krishna, Vamsi Mootha, Salvatore DiMauro, and Michio Hirano
Session Information: P05.139, Child Neurology/Developmental Neurobiology: Genetics
Presentation Time:, Wednesday, April 25, 2:00-7:00 pm
Changes on Dynamic Cerebral Autoregulation are Associated with Delayed Cerebral Ischemia in Patients with Aneurysmal Subarachnoid Hemorrhage
Background/Significance: Early identification of vasospasm prior to symptom onset would allow for proactive treatment to prevent delayed cerebral ischemia (DCI) in subarachnoid hemorrhage (SAH). This study demonstrates that dynamic cerebral autoregulation (DCA) -- a noninvasive means of assessing cerebral blood flow regulation by determining the independence of low-frequency temporal oscillations of systemic blood pressure and cerebral flow velocities -- may be useful for early detection of symptomatic vasospasm. A larger cohort study of SAH patients is currently underway.
Authors: Santiago Ortega-Gutierrez, Nils Petersen, Andres Reccius, Amy Huang, Guillermo Linares-Tapia, Randolph Marshall, and Neeraj Badjatia
Session Information: P06.257, Critical Care/Emergency Neurology/Trauma
Presentation Time: Thursday, April 26, 7:30 am:00 pm
MERRF and Kearns-Sayre Overlap Syndrome Due to the Mitochondrial DNA M.3291T>C Mutation
Background/Significance: This study describes the first case of MERRF-KSS overlap syndrome (an overlap of two distinct mitochondrial disorders) associated with the m.3291T>C mutation in the tRNALeu(UUR) gene. This is a new phenotype-genotype association in mitochondrial disorders. The mechanisms by which mutations in transfer RNA affect mitochondrial respiratory chain activities and how this correlates with the clinical presentation are still largely unknown. The study data reinforce the well-established concept that in mitochondrial DNA-related disorders, the same genetic abnormality can be associated with a wide spectrum of phenotypes (clinical presentations), as well as the observation that tRNALeu(UUR) is a hotspot for mitochondrial DNA mutations.
Authors: Valentina Emmanuele, David Silvers, Evangelia Sotiriou, Kurenai Tanji, Salvatore DiMauro, and Michio Hirano
Session Information: P07.209, Mitochondrial Myopathies
Presentation Time: Thursday, April 26, 2:00-6:30 pm
EMBARGO NOTE: The embargo for all abstracts to be presented at the 64th Annual Meeting is in effect until the date and time of the presentation unless otherwise noted on the abstract and/or press release. If there are questions, please contact the AAN media and public relations team.