Lancet Neurol. 2013 Aug;12(8):822-38. doi: 10.1016/S1474-4422(13)70124-8.

Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration.

Wardlaw JM, Smith EE, Biessels GJ, Cordonnier C, Fazekas F, Frayne R, Lindley RI, O'Brien JT, Barkhof F, Benavente OR, Black SE,Brayne C, Breteler M, Chabriat H, Decarli C, de Leeuw FE, Doubal F, Duering M, Fox NC, Greenberg S, Hachinski V, Kilimann I, Mok V,Oostenbrugge Rv, Pantoni L, Speck O, Stephan BC, Teipel S, Viswanathan A, Werring D, Chen C, Smith C, van Buchem M, Norrving B,Gorelick PB, Dichgans M; STandards for ReportIng Vascular changes on nEuroimaging (STRIVE v1).

Source

Neuroimaging Sciences, University of Edinburgh, Edinburgh, UK; Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK; Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK. Electronic address: joanna.wardlaw@ed.ac.uk.

Abstract

Cerebral small vessel disease (SVD) is a common accompaniment of ageing. Features seen on neuroimaging include recent small subcortical infarcts, lacunes, white matter hyperintensities, perivascular spaces, microbleeds, and brain atrophy. SVD can present as a stroke or cognitive decline, or can have few or no symptoms. SVD frequently coexists with neurodegenerative disease, and can exacerbate cognitive deficits, physical disabilities, and other symptoms of neurodegeneration. Terminology and definitions for imaging the features of SVD vary widely, which is also true for protocols for image acquisition and image analysis. This lack of consistency hampers progress in identifying the contribution of SVD to the pathophysiology and clinical features of common neurodegenerative diseases. We are an international working group from the Centres of Excellence in Neurodegeneration. We completed a structured process to develop definitions and imaging standards for markers and consequences of SVD. We aimed to achieve the following: first, to provide a common advisory about terms and definitions for features visible on MRI; second, to suggest minimum standards for image acquisition and analysis; third, to agree on standards for scientific reporting of changes related to SVD on neuroimaging; and fourth, to review emerging imaging methods for detection and quantification of preclinical manifestations of SVD. Our findings and recommendations apply to research studies, and can be used in the clinical setting to standardise image interpretation, acquisition, and reporting. This Position Paper summarises the main outcomes of this international effort to provide the STandards for ReportIng Vascular changes on nEuroimaging (STRIVE).

Discovering rare diseses: King Denborough Syndrome

Neuromuscul Disord. 2011 Jun;21(6):420-7. doi: 10.1016/j.nmd.2011.03.006. Epub 2011 Apr 22.

King-Denborough syndrome with and without mutations in the skeletal muscle ryanodine receptor (RYR1) gene.

Dowling JJ, Lillis S, Amburgey K, Zhou H, Al-Sarraj S, Buk SJ, Wraige E, Chow G, Abbs S, Leber S, Lachlan K, Baralle D, Taylor A,Sewry C, Muntoni F, Jungbluth H.

Source

Division of Pediatric Neurology, Pediatric Neuromuscular Clinic, 5328 BSRB, 109 Zina Pitcher Place, Ann Arbor, MI, USA.

Abstract

King-Denborough syndrome (KDS), first described in 1973, is a rare condition characterised by the triad of dysmorphic features, myopathy, and malignant hyperthermia susceptibility (MHS). Autosomal dominant inheritance with variable expressivity has been reported in several cases. Mutations in the skeletal muscle ryanodine receptor (RYR1) gene have been implicated in a wide range of myopathies such as central core disease (CCD), the malignant hyperthermia (MH) susceptibility trait and one isolated patient with KDS. Here we report clinical, pathologic and genetic features of four unrelated patients with KDS. Patients had a relatively uniform clinical presentation but muscle biopsy findings were highly variable. Heterozygous missense mutations in RYR1 were uncovered in three out of four families, of which one mutation was novel and two have previously been reported in MH. Further RyR1 protein expression studies performed in two families showed marked reduction of the RyR1 protein, indicating the presence of allelic RYR1 mutations not detectable on routine sequencing and potentially explaining marked intrafamilial variability. Our findings support the hypothesis that RYR1 mutations are associated with King-Denborough syndrome but that further genetic heterogeneity is likely.

Discovering rare diseases: Schwartz Jampell disease

Spec Care Dentist. 2012 Jun;32(3):105-11. doi: 10.1111/j.1754-4505.2012.00249.x. Epub 2012 Apr 26.

Schwartz-Jampel syndrome: a review of the literature and case report.

Mallineni SK, Yiu CK, King NM.

Source

Faculty of Dentistry, University of Hong Kong, Hong Kong SAR, China.

Abstract

Schwartz-Jampel syndrome (SJS) is a rare autosomal recessive skeletal dysplasia associated with myotonia. The manifestations of SJS include short stature, blepharophimosis, and skeletal anomalies. The combination of skeletal and muscular abnormalities may result in oro-dental manifestations such as atypical facies, with micrognathia, microstomia, pursed lips, crossbite, cleft palate, as well as mandibular hypoplasia, the risk of dentigerous cysts, and impacted teeth. The use of general anesthesia in patients with SJS is dangerous, as there is a risk of malignant hyperthermia. The purpose of this paper is to describe a 3-year-old Chinese boy diagnosed with SJS at birth. His intra-oral examination revealed significant dental findings such as dentin defects with generalized attrition and hypodontia of the permanent dentition. Comprehensive dental treatment was provided at the same time as lower right limb surgery to reduce the potential complications with general anesthesia.

Autoimmune disease preceding amyotrophic lateral sclerosis

Objective: To study whether the risk of amyotrophic lateral sclerosis (ALS) is increased in people with prior autoimmune disease.

Methods: An all-England hospital record-linkage dataset spanning 1999–2011 was used. Cohorts were constructed of people with each of a range of autoimmune diseases; the incidence of ALS in each disease cohort was compared with the incidence of ALS in a cohort of individuals without prior admission for the autoimmune disease.

Results: There were significantly more cases than expected of ALS associated with a prior diagnosis of asthma, celiac disease, younger-onset diabetes (younger than 30 years), multiple sclerosis, myasthenia gravis, myxedema, polymyositis, Sjögren syndrome, systemic lupus erythematosus, and ulcerative colitis.

Conclusions: Autoimmune disease associations with ALS raise the possibility of shared genetic or environmental risk factors.

Neurology 10.1212/WNL.0b013e3182a6cc13

Late-onset anti–NMDA receptor encephalitis

Objective: To describe the clinical features and outcome of anti–NMDA receptor (NMDAR) encephalitis in patients ≥45 years old.

Method: Observational cohort study.

Results: In a cohort of 661 patients with anti-NMDAR encephalitis, we identified 31 patients ≥45 years old. Compared with younger adults (18–44 years), older patients were more often male (45% vs 12%, p < 0.0001), had lower frequency of tumors (23% vs 51%, p = 0.002; rarely teratomas), had longer median time to diagnosis (8 vs 4 weeks, p= 0.009) and treatment (7 vs 4 weeks, p = 0.039), and had less favorable outcome (modified Rankin Scale score 0–2 at 2 years, 60% vs 80%, p < 0.026). In multivariable analysis, younger age (odds ratio [OR] 0.15, confidence interval [CI] 0.05–0.39, p = 0.0001), early treatment (OR 0.60, CI 0.47–0.78, p < 0.0001), no need for intensive care (OR 0.09, CI 0.04–0.22, p < 0.0001), and longer follow-up (p < 0.0001) were associated with good outcome. Rituximab and cyclophosphamide were effective when first-line immunotherapies failed (OR 2.93, CI 1.10–7.76, p = 0.031). Overall, 60% of patients older than 45 years had full or substantial recovery at 24 months follow-up.

Conclusions: Anti-NMDAR encephalitis is less severe in patients ≥45 years old than in young adults, but the outcome is poorer in older patients. In this age group, delays in diagnosis and treatment are more frequent than in younger patients. The frequency of underlying tumors is low, but if present they are usually carcinomas instead of teratomas in younger patients. Early and aggressive immunotherapy will likely improve the clinical outcome.

Neurology 10.1212/WNL.0b013e3182a4a49c

An index to identify stroke-related vs incidental patent foramen ovale in cryptogenic stroke

Objective: We aimed to create an index to stratify cryptogenic stroke (CS) patients with patent foramen ovale (PFO) by their likelihood that the stroke was related to their PFO.

Methods: Using data from 12 component studies, we used generalized linear mixed models to predict the presence of PFO among patients with CS, and derive a simple index to stratify patients with CS. We estimated the stratum-specific PFO-attributable fraction and stratum-specific stroke/TIA recurrence rates.

Results: Variables associated with a PFO in CS patients included younger age, the presence of a cortical stroke on neuroimaging, and the absence of these factors: diabetes, hypertension, smoking, and prior stroke or TIA. The 10-point Risk of Paradoxical Embolism score is calculated from these variables so that the youngest patients with superficial strokes and without vascular risk factors have the highest score. PFO prevalence increased from 23% (95% confidence interval [CI]: 19%–26%) in those with 0 to 3 points to 73% (95% CI: 66%–79%) in those with 9 or 10 points, corresponding to attributable fraction estimates of approximately 0% to 90%. Kaplan-Meier estimated stroke/TIA 2-year recurrence rates decreased from 20% (95% CI: 12%–28%) in the lowest Risk of Paradoxical Embolism score stratum to 2% (95% CI: 0%–4%) in the highest.

Conclusion: Clinical characteristics identify CS patients who vary markedly in PFO prevalence, reflecting clinically important variation in the probability that a discovered PFO is likely to be stroke-related vs incidental. Patients in strata more likely to have stroke-related PFOs have lower recurrence risk.

Neurology 2013

FDA Drug Safety Communication: FDA requires label changes to warn of risk for possibly permanent nerve damage from antibacterial fluoroquinolone drugs taken by mouth or by injection

http://www.fda.gov/downloads/Drugs/DrugSafety/UCM365078.pdf

Safety Announcement

[8-15-2013] The U.S. Food and Drug Administration (FDA) has required the drug labels and Medication. Guides for all fluoroquinolone antibacterial drugs be updated to better describe the serious side effect  of peripheral neuropathy. This serious nerve damage potentially caused by fluoroquinolones may occur soon after these drugs are taken and may be permanent. The risk of peripheral neuropathy occurs only with fluoroquinolones that are taken by mouth or by  injection. Approved fluoroquinolone drugs include levofloxacin (Levaquin), ciprofloxacin (Cipro),  moxifloxacin (Avelox), norfloxacin (Noroxin), ofloxacin (Floxin), and gemifloxacin (Factive). The topical  formulations of fluoroquinolones, applied to the ears or eyes, are not known to cause this risk.  If a patient develops symptoms of peripheral neuropathy, the fluoroquinolone should be stopped, and  the patient should be switched to another, non-fluoroquinolone antibacterial drug, unless the benefit of continued treatment with a fluoroquinolone outweighs the risk. Peripheral neuropathy is a nerve  disorder occurring in the arms or legs. Symptoms include pain, burning, tingling, numbness, weakness, 

 r a change in sensation to light touch, pain or temperature, or the sense of body position. It can occur  at any time during treatment with fluoroquinolones and can last for months to years after the drug is stopped or be permanent. Patients using fluoroquinolones who develop any symptoms of peripheral  neuropathy should tell their health care professionals right away.  FDA will continue to evaluate the safety of drugs in the fluoroquinolone class and will communicate with  the public again if additional information becomes available