Sacral neuromodulation for neurogenic lower urinary tract dysfunction: systematic review and meta-analysis

Context Treatment of neurogenic lower urinary tract dysfunction (LUTD) is a challenge, because conventional therapies often fail. Sacral neuromodulation (SNM) has become a well-established therapy for refractory non-neurogenic LUTD, but its value in patients with a neurologic cause is unclear. Objective To assess the efficacy and safety of SNM for neurogenic LUTD. Evidence acquisition Studies were identified by electronic search of PubMed, EMBASE, and ScienceDirect (on 15 April 2010) and hand search of reference lists and review articles. SNM articles were included if they reported on efficacy and/or safety of tested and/or permanently implanted patients suffering from neurogenic LUTD. Two reviewers independently selected studies and extracted data. Study estimates were pooled using Bayesian random-effects meta-analysis. Evidence synthesis Of the 26 independent studies (357 patients) included, the evidence level ranged from 2b to 4 according to the Oxford Centre for Evidence-Based Medicine. Half (n = 13) of the included studies reported data on both test phase and permanent SNM; the remaining studies were confined to test phase (n = 4) or permanent SNM (n = 9). The pooled success rate was 68% for the test phase (95% credibility interval [CrI], 50–87) and 92% (95% CrI, 81–98%) for permanent SNM, with a mean follow-up of 26 mo. The pooled adverse event rate was 0% (95% CrI, 0–2%) for the test phase and 24% (95% CrI, 6–48%) for permanent SNM. Conclusions There is evidence indicating that SNM may be effective and safe for the treatment of patients with neurogenic LUTD. However, the number of investigated patients is low with high between-study heterogeneity, and there is a lack of randomised, controlled trials. Thus, well-designed, adequately powered studies are urgently needed before more widespread use of SNM for neurogenic LUTD can be recommended.

The prevalence of endothelial dysfunction in patients with and without coronary artery disease

Endothelial dysfunction (ED) is frequently present in patients presenting with acute or stable coronary artery disease (CAD), but it is also found in patients presenting with chest pain without angiographic coronary lesions.

Nerve excitability studies characterize Kv1.1 fast potassium channel dysfunction in patients with episodic ataxia type 1

Episodic ataxia type 1 is a neuronal channelopathy caused by mutations in the KCNA1 gene encoding the fast K(+) channel subunit K(v)1.1. Episodic ataxia type 1 presents with brief episodes of cerebellar dysfunction and persistent neuromyotonia and is associated with an increased incidence of epilepsy. In myelinated peripheral nerve, K(v)1.1 is highly expressed in the juxtaparanodal axon, where potassium channels limit the depolarizing afterpotential and the effects of depolarizing currents. Axonal excitability studies were performed on patients with genetically confirmed episodic ataxia type 1 to characterize the effects of K(v)1.1 dysfunction on motor axons in vivo. The median nerve was stimulated at the wrist and compound muscle action potentials were recorded from abductor pollicis brevis. Threshold tracking techniques were used to record strength-duration time constant, threshold electrotonus, current/threshold relationship and the recovery cycle. Recordings from 20 patients from eight kindreds with different KCNA1 point mutations were compared with those from 30 normal controls. All 20 patients had a history of episodic ataxia and 19 had neuromyotonia. All patients had similar, distinctive abnormalities: superexcitability was on average 100% higher in the patients than in controls (P < 0.00001) and, in threshold electrotonus, the increase in excitability due to a depolarizing current (20% of threshold) was 31% higher (P < 0.00001). Using these two parameters, the patients with episodic ataxia type 1 and controls could be clearly separated into two non-overlapping groups. Differences between the different KCNA1 mutations were not statistically significant. Studies of nerve excitability can identify K(v)1.1 dysfunction in patients with episodic ataxia type 1. The simple 15 min test may be useful in diagnosis, since it can differentiate patients with episodic ataxia type 1 from normal controls with high sensitivity and specificity.

S100A1 genetically targeted therapy reverses dysfunction of human failing cardiomyocytes

This study investigated the hypothesis whether S100A1 gene therapy can improve pathological key features in human failing ventricular cardiomyocytes (HFCMs).

[Dysfunction of the chemical senses smell and taste]

Dysfunction of the senses of taste and smell may strongly affect our lives. During the last years reliable techniques for the standardized investigation of the 2 senses have been introduced to clinical routine. These techniques are highly standardized and can be easily used, for example, for quality control before and after surgery. Although there are proven therapeutic approaches to taste or smell loss, by far not all patients can be helped. New ideas need to tested within rigorous double-blind studies. The regenerative capacity within the chemical senses provides a major basis for hopes on therapeutic success.

Gustatory dysfunction after mandibular zoster

Varicella zoster, limited to the mandibular nerve, is rare. Classical symptoms are pain, hypesthesia and vesicular eruption restricted to the third trigeminal segment (V3). Little is known on taste affection after mandibular nerve zoster. We report two cases of patients suffering from mandibular zoster associated with subjective taste disorder. In both cases, gustatory measures confirmed ipsilateral hemiageusia of the anterior two-thirds of the tongue. After 2 months, the symptoms regressed and psychophysical measures came back to normal values, whereas post-zoster neuralgia lasted for more than 1 year. Gustatory dysfunction is a possible symptom after mandibular nerve zoster. In contrast to post-zoster neuralgia, taste function seems to recover quickly.

Developmental Brain Dysfunction: Revival and Expansion of Old Concepts Based on New Genetic Evidence

Neurodevelopmental disorders can be caused by many different genetic abnormalities that are individually rare but collectively common. Specific genetic causes, including certain copy number variants and single-gene mutations, are shared among disorders that are thought to be clinically distinct. This evidence of variability in the clinical manifestations of individual genetic variants and sharing of genetic causes among clinically distinct brain disorders is consistent with the concept of developmental brain dysfunction, a term we use to describe the abnormal brain function underlying a group of neurodevelopmental and neuropsychiatric disorders and to encompass a subset of various clinical diagnoses. Although many pathogenic genetic variants are currently thought to be variably penetrant, we hypothesise that when disorders encompassed by developmental brain dysfunction are considered as a group, the penetrance will approach 100%. The penetrance is also predicted to approach 100% when the phenotype being considered is a specific trait, such as intelligence or autistic-like social impairment, and the trait could be assessed using a continuous, quantitative measure to compare probands with non-carrier family members rather than a qualitative, dichotomous trait and comparing probands with the healthy population. Copyright 2013 Elsevier Ltd. All rights reserved.

Systemic vascular dysfunction in patients with chronic mountain sickness

Chronic mountain sickness (CMS) is a major public health problem characterized by exaggerated hypoxemia and erythrocytosis. In more advanced stages, patients with CMS often present with functional and structural changes of the pulmonary circulation, but there is little information on the systemic circulation. In patients with diseases associated with chronic hypoxemia at low altitude, systemic vascular function is altered. We hypothesized that patients with CMS have systemic vascular dysfunction that may predispose them to increased systemic cardiovascular morbidity.

Membrane dysfunction in Andersen-Tawil syndrome assessed by velocity recovery cycles

Andersen-Tawil syndrome (ATS) due to Kir2.1mutations typically manifests as periodic paralysis, cardiac arrhythmias and developmental abnormalities but is often difficult to diagnose clinically. This study was undertaken to determine whether sarcolemmal dysfunction could be identified with muscle velocity recovery cycles (MVRCs).

A mouse model of Schwartz-Jampel syndrome reveals myelinating Schwann cell dysfunction with persistent axonal depolarization in vitro and distal peripheral nerve hyperexcitability when perlecan is lacking

Congenital peripheral nerve hyperexcitability (PNH) is usually associated with impaired function of voltage-gated K(+) channels (VGKCs) in neuromyotonia and demyelination in peripheral neuropathies. Schwartz-Jampel syndrome (SJS) is a form of PNH that is due to hypomorphic mutations of perlecan, the major proteoglycan of basement membranes. Schwann cell basement membrane and its cell receptors are critical for the myelination and organization of the nodes of Ranvier. We therefore studied a mouse model of SJS to determine whether a role for perlecan in these functions could account for PNH when perlecan is lacking. We revealed a role for perlecan in the longitudinal elongation and organization of myelinating Schwann cells because perlecan-deficient mice had shorter internodes, more numerous Schmidt-Lanterman incisures, and increased amounts of internodal fast VGKCs. Perlecan-deficient mice did not display demyelination events along the nerve trunk but developed dysmyelination of the preterminal segment associated with denervation processes at the neuromuscular junction. Investigating the excitability properties of the peripheral nerve suggested a persistent axonal depolarization during nerve firing in vitro, most likely due to defective K(+) homeostasis, and excluded the nerve trunk as the original site for PNH. Altogether, our data shed light on perlecan function by revealing critical roles in Schwann cell physiology and suggest that PNH in SJS originates distally from synergistic actions of peripheral nerve and neuromuscular junction changes.