The first reported familial case of statin-induced immune-mediated necrotizing myopathy associated with anti-hydroxy-3-methylglutaryl-CoA reductase autoantibodies and HLA DRB1*11:01.

Immune-mediated necrotizing myopathy (IMNM) is a rare type of auto-immune myositis, characterized by symmetric muscle pain, proximal weakness, elevated serum CK levels and pathologic findings of necrotized muscle fibers. IMNM may be seronegative, associated with anti-signal recognition particle (SRP) antibodies or anti-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) antibodies, the last widely related with statin use. This last entity affects only 2 to 3 of 100,000 patients under statins.

Case report: Coexistence of myotonia congenita and Brugada syndrome in one family.

Myotonia congenita is a rare neuromuscular disorder caused by mutations resulting in delayed muscle relaxation. Extramuscular manifestations are not considered to be present in chloride skeletal channelopathies, although recently some cardiac manifestations have been described. We report a family with autosomal dominant myotonia congenita and Brugada syndrome.

Electrochemical Skin Conductance Alterations during Spinal Cord Stimulation: An Experimental Study.

Despite the well-known clinical effects of spinal cord stimulation (SCS), the mechanisms of action have not yet been fully unraveled. The primary aim of this study was to measure whether electrochemical skin conductance, as a measure of peripheral sympathetic autonomic function, is altered by SCS. A second aim was to compare skin conductance levels of patients with failed back surgery syndrome (FBSS) with age- and sex-matched healthy controls.

Bilateral low frequency rTMS of the primary motor cortex may not be a suitable treatment for levodopa-induced dyskinesias in late stage Parkinson's disease.

Background: In late stage Parkinson patients there is an unmet need for new treatments to adequately control motor complications, especially dyskinesias. In several preliminary studies, it has been suggested that applying unilateral low-frequency repetitive transcranial magnetic stimulation (LF rTMS), delivered at the primary motor cortex (MC) or the supplementary motor area (SMA), may reduce levodopa-induced dyskinesias (LID), either in a single or a multiple session stimulation protocol. In our current clinical research, we examined whether single or multiple (accelerated) sham-controlled bilateral LF rTMS session(s) applied to the primary motor cortices are able to reduce levodopa-induced dyskinesias in patients with advanced Parkinson's disease.

Headache associated with cough: a review.

Headache only triggered by coughing is a rather uncommon condition. The aim of the present review is to present an overview of the diagnosis, clinical characteristics, pathophysiology and treatment of both primary and symptomatic cough headache and discuss other relevant headache disorders affected by coughing. The diagnosis of primary cough headache is made when headache is brought on and occurs only in association with coughing, straining or a Valsalva manoeuvre and in the absence of any abnormalities on neuro-imaging.

Pre-stroke use of statins on stroke outcome: a meta-analysis of observational studies.

Background: Animal pre-clinical studies suggest that statins may have neuroprotective effects in acute ischaemic stroke. Statins might also increase the risk of developing haemorrhagic transformation after thrombolytic treatment.

Methods: We performed a systematic review and included studies that compared good functional outcome, defined as a modified Rankin Scale (mRS) score < or = 2 at 3 months, in-hospital mortality and risk of symptomatic haemorrhagic transformation, between pre -stroke statin users and non users with acute ischaemic stroke.

Small molecules enhance autophagy and reduce toxicity in Huntington's disease models.

The target of rapamycin proteins regulate various cellular processes including autophagy, which may play a protective role in certain neurodegenerative and infectious diseases. Here we show that a primary small-molecule screen in yeast yields novel small-molecule modulators of mammalian autophagy. We first identified new small-molecule enhancers (SMER) and inhibitors (SMIR) of the cytostatic effects of rapamycin in Saccharomyces cerevisiae.

Lithium induces autophagy by inhibiting inositol monophosphatase.

Macroautophagy is a key pathway for the clearance of aggregate-prone cytosolic proteins. Currently, the only suitable pharmacologic strategy for up-regulating autophagy in mammalian cells is to use rapamycin, which inhibits the mammalian target of rapamycin (mTOR), a negative regulator of autophagy. Here we describe a novel mTOR-independent pathway that regulates autophagy.

Neisseria meningitidis-induced death of cerebrovascular endothelium: mechanisms triggering transcriptional activation of inducible nitric oxide synthase.

The intense host response to meningococcus reflects marked functional and morphological alterations in blood-brain barriers. We showed previously that mouse-derived cerebrovascular endothelium responded to meningococcal lysates with a robust nitric oxide (NO) response, resulting in the loss of cell viability. To understand how the NO synthase-2 gene in endothelium is activated by meningococcus, we investigated upstream roles for specific protein kinases.