progetto NEU- NEUROLOGIA EMERGENZA URGENZA

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Il Gruppo di Lavoro Intersocietario sulla Neurologia dell’Emergenza-Urgenza di SIN e SNO, con il coordinamento di G. Micieli, D. Toni, R. Sterzi, F. De Falco, G. Tedeschi, D. Consoli, D. Inzitari, A. Cavallini composto da 10 gruppi di studio a cui contribuiscono oltre 40 neurologi italiani attivi in differenti aree terapeutiche, ha ideato il “Progetto NEU” con l'obiettivo di diventare un punto di riferimento per tutti gli specialisti del settore. 

10 algoritmi decisionali,destinati a supportare lo specialista nel percorso diagnostico in situazioni di urgenza neurologica, nonché un valido strumento di formazione e aggiornamento.

I contenuti del Progetto NEU sono stati sviluppati in modo originale dal Gruppo di Lavoro Intersocietario sulla Neurologia di Emergenza- Urgenza di SIN e SNO e si basano sulla esperienza clinica degli specialisti del Gruppo di Lavoro. In nessun caso i contenuti del Progetto NEU sono sostitutivi delle Linee Guida di riferimento.

Il Progetto NEU consentirà agli specialisti che operano nella neurologia di emergenza/urgenza la consultazione online degli algoritmi decisionali per i quadri clinici neurologici che si presentano. In nessun caso gli algoritmi decisionali possono sostituirsi alla decisione diagnostico-terapeutica dello specialista che rimane l’unico responsabile delle proprie scelte, sia diagnostiche che terapeutiche.

Discovering POTS syndrome

http://circ.ahajournals.org/content/127/23/2336.long

Circulation. 2013; 127: 2336-2342

Discovering strange syndromes: AAA and Aladyn

Endocr Res. 2004 Nov;30(4):891-9.

The triple A syndrome is due to mutations in ALADIN, a novel member of the nuclear pore complex.

Huebner A, Kaindl AM, Knobeloch KP, Petzold H, Mann P, Koehler K.

Source

Children's Hospital, Technical University, Dresden, Germany. Angela.Huebner@mailbox.tu-dresden.de

Abstract

The triple A syndrome (MIM#231550) is a rare autosomal recessive disorder characterized by adrenocorticotropic hormone (ACTH) resistant adrenal failure, achalasia, alacrima, and a variety of neurological and dermatological features. The triple A syndrome is caused by mutations in the AAAS gene, which encodes a protein known as ALADIN (ALacrima Achalasia aDrenal Insufficiency Neurologic disorder). ALADIN is a new WD-repeat protein that has no significant homology to any previously identified WD-repeat protein. It has been shown that it colocalizes with nuclear pore complexes (NPCs), a finding that strongly suggests an involvement of ALADIN in nucleocytoplasmic transport. An investigation of 110 families with triple A syndrome disclosed mutation hot spots including Q15K (exon 1), and S293P (exon 8), which occur in 17 and 21 families from different geographical regions, respectively. The variable phenotype of all patients cannot be correlated with the localization and the nature of the ALADIN mutations. Thus, modifying genes/factors may be involved in the progression of this neurodegenerative disease. The lack of AAAS mutations in eight patients and negative linkage to chromosome 12q13 in three families are suggestive of genetic heterogeneity. To examine the cellular localization of ALADIN mutants causing triple A syndrome, we investigated nine different ALADIN-mutants: 2 nonsense (W84X, Q456X), 2 frameshift (F157fsX171, G397fsX414) and 5 point mutations (Q15K, L25P, H160R, S263P, L381R) by transfection experiments with green fluorescence protein. Mutants were predominantly localized in the cytoplasm, but also found in the nucleus indicating that ALADIN is essential for NPC targeting. To investigate physiological functions of ALADIN in vivo, we generated and analysed Aaas-/- knockout mice by homologous recombination in embryonic stem cells. Surprisingly, required animals lack any gross abnormality in adrenal and nervous system function. Further studies have to investigate the role of ALADIN at NPCs and to identify interacting proteins. Functional analyses of ALADIN may permit further understanding of its role for adrenocortical function and neurodevelopment.

Discovering strange cases: Harlequin Syndrome

Harlequin syndrome - one face of many etiologies

Gunnar Wasner*, Rainer Maag, Janne Ludwig, Andreas Binder, Jörn Schattschneider, Robert Stingele and Ralf Baron

Background A 55-year-old woman presented to hospital with a 3-month history of asymmetric facial flushing of the skin during exertion, and an 18-month history of left-sided ptosis and miosis. Detailed medical history analysis revealed that a palpable node measuring 0.8  1.2  1.2 cm (volume 1.1 ml) had been discovered 2 years previously, within the left lobe of an otherwise uncomplicated goiter that had been successfully managed for 20 years. Otherwise, the patient was healthy.

Investigations Neurological examination, autonomic testing, duplex ultrasonography, scintigraphy and MRI.

Diagnosis Harlequin syndrome following a lesion of the preganglionic sympathetic efferents, caused by neurovascular compression of the sympathetic chain between the stellate and superior cervical ganglion brought about by an elongated inferior thyroid artery.

Management Explanation of pathophysiology and benign nature of the condition.

Nature Clinical Practice Neurology (2005) 1, 54-59

http://www.nature.com/nrneurol/journal/v1/n1/full/ncpneuro0040.html

Clopidogrel with Aspirin in Acute Minor Stroke or Transient Ischemic Attack

Yongjun Wang, M.D., Yilong Wang, M.D., Ph.D., Xingquan Zhao, M.D., Ph.D., Liping Liu, M.D., Ph.D., David Wang, D.O., F.A.H.A., F.A.A.N., Chunxue Wang, M.D., Ph.D., Chen Wang, M.D., Hao Li, Ph.D., Xia Meng, M.D., Ph.D., Liying Cui, M.D., Ph.D., Jianping Jia, M.D., Ph.D., Qiang Dong, M.D., Ph.D., Anding Xu, M.D., Ph.D., Jinsheng Zeng, M.D., Ph.D., Yansheng Li, M.D., Ph.D., Zhimin Wang, M.D., Haiqin Xia, M.D., and S. Claiborne Johnston, M.D., Ph.D. for the CHANCE Investigators

June 26, 2013DOI: 10.1056/NEJMoa1215340

BACKGROUND

Stroke is common during the first few weeks after a transient ischemic attack (TIA) or minor ischemic stroke. Combination therapy with clopidogrel and aspirin may provide greater protection against subsequent stroke than aspirin alone.

METHODS

In a randomized, double-blind, placebo-controlled trial conducted at 114 centers in China, we randomly assigned 5170 patients within 24 hours after the onset of minor ischemic stroke or high-risk TIA to combination therapy with clopidogrel and aspirin (clopidogrel at an initial dose of 300 mg, followed by 75 mg per day for 90 days, plus aspirin at a dose of 75 mg per day for the first 21 days) or to placebo plus aspirin (75 mg per day for 90 days). All participants received open-label aspirin at a clinician-determined dose of 75 to 300 mg on day 1. The primary outcome was stroke (ischemic or hemorrhagic) during 90 days of follow-up in an intention-to-treat analysis. Treatment differences were assessed with the use of a Cox proportional-hazards model, with study center as a random effect.

RESULTS

Stroke occurred in 8.2% of patients in the clopidogrel–aspirin group, as compared with 11.7% of those in the aspirin group (hazard ratio, 0.68; 95% confidence interval, 0.57 to 0.81; P<0.001). Moderate or severe hemorrhage occurred in seven patients (0.3%) in the clopidogrel–aspirin group and in eight (0.3%) in the aspirin group (P=0.73); the rate of hemorrhagic stroke was 0.3% in each group.

CONCLUSIONS

Among patients with TIA or minor stroke who can be treated within 24 hours after the onset of symptoms, the combination of clopidogrel and aspirin is superior to aspirin alone for reducing the risk of stroke in the first 90 days and does not increase the risk of hemorrhage. (Funded by the Ministry of Science and Technology of the People's Republic of China; CHANCE ClinicalTrials.gov number, NCT00979589.)

NEJM 2013

Anti MOG

The spectrum of MOG autoantibody-associated demyelinating diseases

Markus Reindl, Franziska Di Pauli, Kevin Rostásy & Thomas Berger  

of page

Abstract

Myelin oligodendrocyte glycoprotein (MOG) has been identified as a target of demyelinating autoantibodies in animal models of inflammatory demyelinating diseases of the CNS, such as multiple sclerosis (MS). Numerous studies have aimed to establish a role for MOG antibodies in patients with MS, although the results have been controversial. Cell-based immunoassays using MOG expressed in mammalian cells have demonstrated the presence of high-titre MOG antibodies in paediatric patients with acute disseminated encephalomyelitis, MS, aquaporin-4-seronegative neuromyelitis optica, or isolated optic neuritis or transverse myelitis, but only rarely in adults with these disorders. These studies indicate that MOG antibodies could be associated with a broad spectrum of acquired human CNS demyelinating diseases. This Review article discusses the current literature on MOG antibodies, their potential clinical relevance, and their role in the pathogenesis of MOG antibody-associated demyelinating disorders.

Nature Reviews Neurology, advance online publication, Published online 25 June 2013 |doi:10.1038/nrneurol.2013.118

SCA 37

Importance  To provide clinical and genetic diagnoses for patients' conditions, it is important to identify and characterize the different subtypes of spinocerebellar ataxia (SCA).

Objective  To clinically and genetically characterize a Spanish kindred with pure SCA presenting with altered vertical eye movements.

Design  Family study of ambulatory patients. Electro-oculographic and genetics studies were performed in 2 referral university centers.

Setting  Primary care institutional center in Spain.

Participants  Thirty-six participants from a large Spanish kindred were clinically examined, and 33 family members were genetically examined. Detailed clinical data were obtained from 9 affected relatives. Two ataxic siblings and 2 asymptomatic family members were examined using an enhanced clinical protocol for a follow-up period of 7 years.

Main Outcomes and Measures  High-density genome-wide single-nucleotide polymorphism arrays, along with microsatellite analysis, and genetic linkage studies were performed. Whole-exome sequencing was used for 2 affected relatives. For most patients, the initial symptoms included falls, dysarthria, or clumsiness followed by a complete cerebellar syndrome. For all 9 affected relatives, we observed altered vertical eye movements, as initial ocular signs for 3 of them and for the 2 asymptomatic family members, all having inherited the risk haplotype. Neuroimaging showed isolated cerebellar atrophy.

Results  Initial genome-wide linkage analysis revealed suggestive linkage to chromosome 1p32. Multipoint analysis and haplotype reconstruction further traced this SCA locus to a 0.66-cM interval flanked by D1S200 and D1S2742 (zmax = 6.539; P < .0001). The causative mutation was unidentified by exome sequencing.

Conclusions and Relevance  We report a new subtype of SCA presenting in patients as slow progressing ataxia with altered vertical eye movements linked to a 11-megabase interval on 1p32. The Human Genome Nomenclature Committee has assigned this subtype of ataxia the designation SCA37.

JAMA Neurol. 2013;70(6):764-771. doi:10.1001/jamaneurol.2013.2311.

Nature Reviews Neurology June 2013