Enhancement of K+ conductance improves in vitro the contraction force of skeletal muscle in hypokalemic periodic paralysis

An abnormal ratio between Na+ and K+ conductances seems to be the cause for the depolarization and paralysis of skeletal muscle in primary hypokalemic periodic paralysis. Recently we have shown that the k+ channel opener cromakalim hyperpolarizes mammalian skeletal muscle fibers. Now we have studied the effects of this drug on the twitch force of muscle biopsies from normal and diseased human skeletal muscle. Cromakalim had little effect on the twitch force of normal muscle whereas it strongly improved the contraction force of fibers from patients suffering from hypokalemic periodic paralysis. Recordings of intracellular K+ and Cl- activities in human muscle and isolated rat soleus muscle support the view that cromakalim enhances the membrane K+ conductance (gK+). These data indicate that K+ channel openers may have a beneficial effect in primary hypokalemic periodic paralysis

Studies of intercellular invasion in vitro using rabbit peritoneal neutrophil granulocytes (PMNS). I. Role of contact inhibition of locomotion.

Intercellular invasion is the active migration of cells on one type into the interiors of tissues composed of cells of dissimilar cell types. Contact paralysis of locomotion is the cessation of forward extension of the pseudopods of a cell as a result of its collision with another cell. One hypothesis to account for intercellular invasion proposes that a necessary condition for a cell type to be invasive to a given host tissue is that it lack contact paralysis of locomotion during collision with cells of that host tissue. The hypothesis has been tested using rabbit peritoneal neutrophil granulocytes (PMNs) as the invasive cell type and chick embryo fibroblasts as the host tissue. In organ culture, PMNs rapidly invade aggregates of fibroblasts. The behavior of the pseudopods of PMNs during collision with fibroblasts was analyzed for contact paralysis by a study of time-lapse films of cells in mixed monolayer culture. In monolayer culture, PMNs show little sign of paralysis of the pseudopods upon collision with fibroblasts and thus conform in their behavior to that predicted by the hypothesis

Recovery from acidosis is a robust trigger for loss of force in murine hypokalemic periodic paralysis.

Periodic paralysis is an ion channelopathy of skeletal muscle in which recurrent episodes of weakness or paralysis are caused by sustained depolarization of the resting potential and thus reduction of fiber excitability. Episodes are often triggered by environmental stresses, such as changes in extracellular K+, cooling, or exercise. Rest after vigorous exercise is the most common trigger for weakness in periodic paralysis, but the mechanism is unknown. Here, we use knock-in mutant mouse models of hypokalemic periodic paralysis (HypoKPP; NaV1.4-R669H or CaV1.1-R528H) and hyperkalemic periodic paralysis (HyperKPP; NaV1.4-M1592V) to investigate whether the coupling between pH and susceptibility to loss of muscle force is a possible contributor to exercise-induced weakness. In both mouse models, acidosis (pH 6.7 in 25% CO2) is mildly protective, but a return to pH 7.4 (5% CO2) unexpectedly elicits a robust loss of force in HypoKPP but not HyperKPP muscle. Prolonged exposure to low pH (tens of minutes) is required to cause susceptibility to post-acidosis loss of force, and the force decrement can be prevented by maneuvers that impede Cl- entry. Based on these data, we propose a mechanism for post-acidosis loss of force wherein the reduced Cl- conductance in acidosis leads to a slow accumulation of myoplasmic Cl- A rapid recovery of both pH and Cl- conductance, in the context of increased [Cl]in/[Cl]out, favors the anomalously depolarized state of the bistable resting potential in HypoKPP muscle, which reduces fiber excitability. This mechanism is consistent with the delayed onset of exercise-induced weakness that occurs with rest after vigorous activity

Andersen-Tawil syndrome: report of 3 novel mutations and high risk of symptomatic cardiac involvement.

IntroductionAndersen-Tawil syndrome (ATS) is a potassium channelopathy affecting cardiac and skeletal muscle. Periodic paralysis is a presenting symptom in some patients, whereas, in others, symptomatic arrhythmias or prolongation of QT in echocardiographic recordings will lead to diagnosis of ATS. Striking intrafamilial variability of expression of KCNJ2 mutations and rarity of the syndrome may lead to misdiagnosis.MethodsWe report 15 patients from 8 Polish families with ATS, including 3 with novel KCNJ2 mutations.ResultsAll patients had dysmorphic features; periodic paralysis affected males more frequently than females (80% vs. 20%), and most attacks were normokalemic. Two patients (with T75M and T309I mutations) had aborted sudden cardiac death. An implantable cardioverter-defibrillator was utilized in 40% of cases.ConclusionsKCNJ2 mutations cause a variable phenotype, with dysmorphic features seen in all patients studied, a high penetrance of periodic paralysis in males and ventricular arrhythmia with a risk of sudden cardiac death

Familial paroxysmal hypokalaemic paralysis (hypoKPP)

Case Summary: Demographic Details: Mr. SF, male, South African was referred by his general practitioner A 26-year-old South African gentleman was referred to the Neurology Outpatient department due to occasional episodes of bilateral muscle weakness in the lower limbs. The attacks last for approximately 1 hour and may result in complete muscle paralysis. The severe attacks of bilateral lower limb paralysis are uncommon. The most severe attack he had ever experienced lasted for 19 hours when he was 19 years of age. Mr. SF noticed that stress, carbohydrate-rich meals and exercise triggered recurrent attacks of muscle weakness. The patient’s grandfather, father and sister have been diagnosed with ‘Familial Paroxysmal Hypokalaemic Paralysis’ (hypoKPP). The father had a positive genetic diagnosis from a muscle biopsy. Mr. SF believes that he has inherited the genetic condition, however, he was never tested for the mutation. When the patient suffers an attack of muscle weakness, he takes potassium supplements and rests at home and symptoms resolve.peer-reviewe

A rare cause of peripheral facial paralysis in childhood in our country: lyme disease

Lyme disease is a zoonosis caused by Spirochetes called Borrelia burgdorferi, involving several areas, such as the skin, heart and central nervous system. In this case report, we present a 10-year-old male who had complaints of fever, extensive oral aphthae, perioral dried sores, rash, blurred vision and peripheral facial paralysis, and was diagnosed with Lyme disease. In this report, we want to emphasize that Lyme disease should be kept in mind for differential diagnosis in patients with fever and peripheral facial paralysis

Has wild poliovirus been eliminated from Nigeria?

Wild poliovirus type 3 (WPV3) has not been seen anywhere since the last case of WPV3-associated paralysis in Nigeria in November 2012. At the time of writing, the most recent case of wild poliovirus type 1 (WPV1) in Nigeria occurred in July 2014, and WPV1 has not been seen in Africa since a case in Somalia in August 2014. No cases associated with circulating vaccine-derived type 2 poliovirus (cVDPV2) have been detected in Nigeria since November 2014. Has WPV1 been eliminated from Africa? Has WPV3 been eradicated globally? Has Nigeria interrupted cVDPV2 transmission? These questions are difficult because polio surveillance is based on paralysis and paralysis only occurs in a small fraction of infections. This report provides estimates for the probabilities of poliovirus elimination in Nigeria given available data as of March 31, 2015. It is based on a model of disease transmission that is built from historical polio incidence rates and is designed to represent the uncertainties in transmission dynamics and poliovirus detection that are fundamental to interpreting long time periods without cases. The model estimates that, as of March 31, 2015, the probability of WPV1 elimination in Nigeria is 84%, and that if WPV1 has not been eliminated, a new case will be detected with 99% probability by the end of 2015. The probability of WPV3 elimination (and thus global eradication) is >99%. However, it is unlikely that the ongoing transmission of cVDPV2 has been interrupted; the probability of cVDPV2 elimination rises to 83% if no new cases are detected by April 2016. Added July 10, 2015: On June 26, a cVDPV2 case was confirmed by the Global Polio Laboratory Network. The date of paralysis was May 16. The case provides new information about cVDPV2 prevalence that is useful for assessing the accuracy of previous predictions and informing an updated forecast for the time to cVDPV2 elimination.Comment: Added model validation section and updated cVDPV2 forecast in response to new case data; expanded material on surveillance sensitivity; additional minor edits; and references added. 24 pages, 4 figure

Surgical Treatment of Facial Paralysis

The management of facial paralysis is one of the most complex areas of reconstructive surgery. Given the wide variety of functional and cosmetic deficits in the facial paralysis patient, the reconstructive surgeon requires a thorough understanding of the surgical techniques available to treat this condition. This review article will focus on surgical management of facial paralysis and the treatment options available for acute facial paralysis (<3 weeks duration), intermediate duration facial paralysis (3 weeks to 2 yr) and chronic facial paralysis (>2 yr). For acute facial paralysis, the main surgical therapies are facial nerve decompression and facial nerve repair. For facial paralysis of intermediate duration, nerve transfer procedures are appropriate. For chronic facial paralysis, treatment typically requires regional or free muscle transfer. Static techniques of facial reanimation can be used for acute, intermediate, or chronic facial paralysis as these techniques are often important adjuncts to the overall management strategy

Opening Access by Overcoming Zeno's Paralysis

Open Access (OA) means free access for all would-be users webwide to all articles published in all peer-reviewed research journals across all scholarly and scientific disciplines. 100% OA is optimal for research, researchers, their institutions, and their funders because it maximizes research access and usage. It is also 100% feasible: authors just need to deposit ("self-archive") their articles on their own institutional websites. Hence 100% OA is inevitable. Yet the few keystrokes needed to reach it have been paralyzed for a decade by a seemingly endless series of phobias (about everything from piracy and plagiarism to posterity and priorities), each easily shown to be groundless, yet persistent and recurring. The cure for this "Zeno's Paralysis" is for researchers' institutions and funders to mandate the keystrokes, just as they already mandate publishing, and for the very same reason: to maximize research usage, impact and progress. 95% of researchers have said they would comply with a self-archiving mandate; 93% of journals have already given self-archiving their blessing; and those institutions that have already mandated it are successfully and rapidly moving toward 100% OA