Tardive and idiopathic oromandibular dystonia: a clinical comparison

OBJECTIVE: Most patients with tardive dystonia have a focal onset involving the cranial-cervical region. Because of its resemblance to idiopathic cranial dystonia, a common form of dystonia, it often poses a diagnostic problem. To compare clinical features and response to botulinum toxin (BTX) injections between patients with tardive and idiopathic oromandibular dystonia (OMD). METHODS: Patients seen in a movement disorder clinic who satisfied the inclusion criteria for tardive or idiopathic OMD were studied. The clinical variables and responses to BTX between the two groups of patients were compared. In the tardive group, we also compared the clinical variables between those with oro-facial-lingual stereotypies, and those without. RESULTS: Twenty four patients with tardive OMD and 92 with idiopathic OMD were studied. There were no differences in the demographic characteristics. Most were women, with duration of symptoms longer than 8 years. The mean duration of neuroleptic exposure was 7.1 (SD 7.9) years. Jaw closure was the most frequent subtype of OMD (tardive=41.7%, idiopathic=51.1%). Idiopathic patients were more likely to have coexistent cervical dystonia (p<0.05), whereas isolated OMD was significantly higher in tardive patients (p<0.05). Limb stereotypies, akathisia, and respiratory dyskinesia were seen only in the tardive OMD. Frequency of oro-facial-lingual stereotypy was significantly higher in the tardive than the idiopathic group (75.0% v 31.5%, p<0.0001). The peak effect of BTX was similar in both groups. CONCLUSIONS: Oro-facial-lingual stereotypies were significantly more frequent in the tardive than the idiopathic group. Presence of stereotypic movements in the limbs, akathisia, and respiratory dyskinesias in patients with OMD strongly suggests prior neuroleptic exposure. Dystonia in tardive OMD is more likely to be restricted to the oromandibular region, whereas in patients with idiopathic OMD, there is often coexistent cervical dystonia. BTX is equally effective in both groups of patients.     

Harmful at non-cytotoxic concentrations: SiO2-SPIONs affect surfactant metabolism and lamellar body biogenesis in A549 human alveolar epithelial cells

The pulmonary delivery of nanoparticles (NPs) is a promising approach in nanomedicine. For the efficient and safe use of inhalable NPs, understanding of NP interference with lung surfactant metabolism is needed. Lung surfactant is predominantly a phospholipid substance, synthesized in alveolar type II cells (ATII), where it is packed in special organelles, lamellar bodies (LBs). In vitro and in vivo studies have reported NPs impact on surfactant homeostasis, but this phenomenon has not yet been sufficiently examined. We showed that in ATII-like A549 human lung cancer cells, silica-coated superparamagnetic iron oxide NPs (SiO₂-SPIONs), which have a high potential in medicine, caused an increased cellular amount of acid organelles and phospholipids. In SiO₂-SPION treated cells, we observed elevated cellular quantity of multivesicular bodies (MVBs), organelles involved in LB biogenesis. In spite of the results indicating increased surfactant production, the cellular quantity of LBs was surprisingly diminished and the majority of the remaining LBs were filled with SiO₂-SPIONs. Additionally, LBs were detected inside abundant autophagic vacuoles (AVs) and obviously destined for degradation. We also observed time- and dose-dependent changes in mRNA expression for proteins involved in lipid metabolism. Our results demonstrate that non-cytotoxic concentrations of SiO₂-SPIONs interfere with surfactant metabolism and LB biogenesis, leading to disturbed ability to reduce hypophase surface tension. To ensure the safe use of NPs for pulmonary delivery, we propose that potential NP interference with LB biogenesis is obligatorily taken into account.     

Animal Models of Parkinson’s Disease: A Gateway to Therapeutics?

Parkinson’s disease (PD) is a progressive, neurodegenerative disorder of unknown etiology, although a complex interaction between environmental and genetic factors has been implicated as a pathogenic mechanism of selected neuronal loss. A better understanding of the etiology, pathogenesis, and molecular mechanisms underlying the disease process may be gained from research on animal models. While cell and tissue models are helpful in unraveling involved molecular pathways, animal models are much better suited to study the pathogenesis and potential treatment strategies. The animal models most relevant to PD include those generated by neurotoxic chemicals that selectively disrupt the catecholaminergic system such as 6-hydroxydopamine; 1-methyl-1,2,3,6-tetrahydropiridine; agricultural pesticide toxins, such as rotenone and paraquat; the ubiquitin proteasome system inhibitors; inflammatory modulators; and several genetically manipulated models, such as α-synuclein, DJ-1, PINK1, Parkin, and leucine-rich repeat kinase 2 transgenic or knock-out animals. Genetic and nongenetic animal models have their own unique advantages and limitations, which must be considered when they are employed in the study of pathogenesis or treatment approaches. This review provides a summary and a critical review of our current knowledge about various in vivo models of PD used to test novel therapeutic strategies.     

Malassezia yeasts activate the NLRP3 inflammasome in antigen‐presenting cells via Syk‐kinase signalling

Although being a normal part of the skin flora, yeasts of the genus Malassezia are associated with several common dermatologic conditions including pityriasis versicolour, seborrhoeic dermatitis (SD), folliculitis, atopic eczema/dermatitis (AE/AD) and dandruff. While Malassezia spp. are aetiological agents of pityriasis versicolour, a causal role of Malassezia spp. in AE/AD and SD remains to be established. Previous reports have shown that fungi such as Candida albicans and Aspergillus fumigatus are able to efficiently activate the NLRP3 inflammasome leading to robust secretion of the pro‐inflammatory cytokine IL‐1β. To date, innate immune responses to Malassezia spp. are not well characterized. Here, we show that different Malassezia species could induce NLRP3 inflammasome activation and subsequent IL‐1β secretion in human antigen‐presenting cells. In contrast, keratinocytes were not able to secrete IL‐1β when exposed to Malassezia spp. Moreover, we demonstrate that IL‐1β secretion in antigen‐presenting cells was dependent on Syk‐kinase signalling. Our results identify Malassezia spp. as potential strong inducers of pro‐inflammatory responses when taken up by antigen‐presenting cells and identify C‐type lectin receptors and the NLRP3 inflammasome as crucial actors in this process.     

The many faces of hemifacial spasm: Differential diagnosis of unilateral facial spasms

Hemifacial spasm is defined as unilateral, involuntary, irregular clonic or tonic movement of muscles innervated by the seventh cranial nerve. Most frequently attributed to vascular loop compression at the root exit zone of the facial nerve, there are many other etiologies of unilateral facial movements that must be considered in the differential diagnosis of hemifacial spasm. The primary purpose of this review is to draw attention to the marked heterogeneity of unilateral facial spasms and to focus on clinical characteristics of mimickers of hemifacial spasm and on atypical presentations of nonvascular cases. In addition to a comprehensive review of the literature on hemifacial spasm, medical records and videos of consecutive patients referred to the Movement Disorders Clinic at Baylor College of Medicine for hemifacial spasm between 2000 and 2010 were reviewed, and videos of illustrative cases were edited. Among 215 patients referred for evaluation of hemifacial spasm, 133 (62%) were classified as primary or idiopathic hemifacial spasm (presumably caused by vascular compression of the ipsilateral facial nerve), and 4 (2%) had hereditary hemifacial spasm. Secondary causes were found in 40 patients (19%) and included Bell's palsy (n = 23, 11%), facial nerve injury (n = 13, 6%), demyelination (n = 2), and brain vascular insults (n = 2). There were an additional 38 patients (18%) with hemifacial spasm mimickers classified as psychogenic, tics, dystonia, myoclonus, and hemimasticatory spasm. We concluded that although most cases of hemifacial spasm are idiopathic and probably caused by vascular compression of the facial nerve, other etiologies should be considered in the differential diagnosis, particularly if there are atypical features. © 2011 Movement Disorder Society     

Determinants of progression of coronary artery calcification in type 2 diabetes role of glycemic control and inflammatory/vascular calcification markers.

OBJECTIVES: This study prospectively evaluated the relationship between cardiovascular risk factors, selected biomarkers (high-sensitivity C-reactive protein [hs-CRP], interleukin [IL]-6, and osteoprotegerin [OPG]), and the progression of coronary artery calcification (CAC) in type 2 diabetic subjects. BACKGROUND: Coronary artery calcification is pathognomonic of coronary atherosclerosis. Osteoprotegerin is a signaling molecule involved in bone remodeling that has been implicated in the regulation of vascular calcification and atherogenesis. METHODS: Three hundred ninety-eight type 2 diabetic subjects without prior coronary disease or symptoms (age 52 +/- 8 years, 61% male, glycated hemoglobin [HbA(1)c] 8 +/- 1.5) were evaluated serially by CAC imaging (mean follow-up 2.5 +/- 0.4 years). Progression/regression of CAC was defined as a change > or =2.5 between the square root transformed values of baseline and follow-up volumetric CAC scores. Demographic data, risk factors, glycemic control, medication use, serum hs-CRP, IL-6, and plasma OPG levels were measured at baseline and follow-up. RESULTS: Two hundred eleven patients (53%) had CAC at baseline. One hundred eighteen patients (29.6%) had CAC progression, whereas 3 patients (0.8%) had regression. Age, male gender, hypertension, baseline CAC, HbA(1)c >7, waist-hip ratio, IL-6, OPG, use of beta-blockers, calcium channel antagonists, angiotensin-converting enzyme (ACE) inhibitors, statins, and Framingham/UKPDS (United Kingdom Prospective Diabetes Study) risk scores were univariable predictors of CAC progression. In the multivariate model, baseline CAC (odds ratio [OR] for CAC >400 = 6.38, 95% confidence interval [CI] 2.63 to 15.5, p < 0.001), HbA(1)c >7 (OR 1.95, CI 1.08 to 3.52, p = 0.03), and statin use (OR 2.27, CI 1.38 to 3.73, p = 0.001) were independent predictors of CAC progression. CONCLUSIONS: Baseline CAC severity and suboptimal glycemic control are strong risk factors for CAC progression in type 2 diabetic subjects.     

Effectiveness of primary percutaneous coronary intervention for acute ST-elevation myocardial infarction from a 5-year single-center experience

Primary percutaneous coronary intervention (PCI) is currently viewed as the preferred reperfusion strategy in patients with ST-elevation acute myocardial infarction (STEMI). This method was introduced in our hospital in 2000. From January 1, 2000, to December 31, 2004, a total of 2,393 consecutive patients with STEMI were admitted (27% transferred from 9 non-PCI hospitals and 31 prehospital emergency units/outpatient clinics). Of these patients, 1,666 (70%) underwent urgent coronary angiography and primary PCI. Platelet glycoprotein llb/llla inhibitors were used in 40% and stent placement, in 78%. Postprocedural Thrombolysis In Myocardial Infarction (TIMI) 3 flow was documented in 86%. Intra-aortic balloon counterpulsation was used in 6%; mechanical ventilation, in 8.6%; and inotropic drugs/vasopressors, in 15.8%. Mortality rates in patients with Killip's class I or II ranged from 1% to 4.9% without negative influence of ischemic time. In patients with Killip's class III or IV, mortality rates increased from 18% to 54% with increasing ischemic delay up to 6 hours (p = 0.06) and remained at around 40% afterward. Independent predictors of mortality were age (odds ratio [OR] 1.29, 95% confidence interval [CI] 1.01 to 1.64, p = 0.04), resuscitated cardiac arrest (OR 2.44, 95% CI 1.18 to 5.05, p = 0.02), and postprocedural TIMI flow (OR 0.31, 95% CI 0.16 to 0.59). Overall mortality rates of patients who underwent a primary PCI strategy from 2000 to 2004 were significantly lower than in the control group of 152 consecutive patients who underwent thrombolysis from 1995 to 1996 (6.2% vs 16.4%; p <0.001). In conclusion, introduction of a primary PCI strategy significantly decreased hospital mortality in our unselected group of patients with STEMI compared with the thrombolytic era. Our study further emphasized the importance of shortening myocardial ischemic time, particularly in the presence of severe heart failure on admission.