Effects of S906T polymorphism on the severity of a novel borderline mutation I692M in Nav 1.4 cause periodic paralysis.

Hyperkalemic periodic paralysis (HyperPP) is a dominantly inherited muscle disease caused by mutations in SCN4A gene encoding skeletal muscle voltage gated Nav 1.4 channels. We identified a novel Nav 1.4 mutation I692M in 14 families out of the 104 genetically identified HyperPP families in the Neuromuscular Centre Ulm and is therefore as frequent as I693T (13 families out of 14 HyperPP families) in Germany. Surprisingly, in 13 families, a known polymorphism S906T was also present. It was on the affected allele in at least 10 families compatible with a possible founder effect in central Europe. All affected members suffered from episodic weakness; myotonia was also common. Compared with I692M patients, I692M-S906T patients had longer weakness episodes, more affected muscles, CK elevation and presence of permanent weakness. Electrophysiological investigation showed that both mutants had incomplete slow inactivation and a hyperpolarizing shift of activation which contribute to membrane depolarization and weakness. Additionally, I692M-S906T significantly enhanced close-state fast inactivation compared with I692M alone, suggesting a higher proportion of inactivated I692M-S906T channels upon membrane depolarization which may facilitate the initiation of weakness episodes and therefore clinical manifestation. Our results suggest that polymorphism S906T has effects on the clinical phenotypic and electrophysiological severity of a novel borderline Nav 1.4 mutation I692M, making the borderline mutation fully penetrant.

Contractile elements in muscular fascial tissue - implications for in-vitro contracture testing for malignant hyperthermia.

Malignant hyperthermia is a dreaded complication of general anaesthesia. Predisposed individuals can be identified using the standardised caffeine/halothane in-vitro contracture test on a surgically dissected skeletal muscle specimen. Skeletal muscle is composed of muscle fibres and interwoven fascial components. Several malignant hyperthermia-associated neuromuscular diseases are associated with an altered connective tissue composition. We analysed adjacent fascial components of skeletal muscle histologically and physiologically. We investigated whether the fascial tissue is sensitive to electrical or pharmacological stimulation in a way similar to the in-vitro contracture test for diagnosing malignant hyperthermia. Using immunohistochemical staining, α-smooth muscle actin-positive cells (myofibroblasts) were detected in the epi-, endo- and perimysium of human fascial tissue. Force measurements on isolated fascial strips after pharmacological challenge with mepyramin revealed that myofascial tissue is actively regulated by myofibroblasts, thereby influencing the biomechanical properties of skeletal muscle. Absence of electrical reactivity and insensitivity to caffeine and halothane suggests that, reassuringly, the malignant hyperthermia diagnostic in-vitro contracture test is not influenced by the muscular fascial tissue.

Characterization of hyperkalemic periodic paralysis: a survey of genetically diagnosed individuals.

This exploratory study aims to create an evidence-based comprehensive characterization of hyperkalemic periodic paralysis (hyperPP). HyperPP is a rare genetic disorder that causes episodes of flaccid paralysis. Disease descriptions in the literature are based upon isolated clinical encounters and case reports. We describe the experience of a large cohort of genetically diagnosed individuals with hyperPP. We surveyed genetically characterized individuals age 18 and over to assess disease comorbidities, diagnostic testing, management, and quality of life issues relevant to hyperPP. Myotonia was reported by 55.8 % of subjects and paramyotonia by 45.3 %. There is a relative risk of 3.6 (p < 0.0001) for thyroid dysfunction compared to the general population. Twenty-five percent of subjects experienced their sentinel attack in the second decade of life. It took an average of 19.4 years and visits to four physicians to arrive at the diagnosis of hyperPP. In addition to limbs and hands being affected during attacks, 26.1 % of subjects reported their breathing musculature was affected and 62.0 % reported their facial muscles were affected. There was a lifelong trend of increasing attack frequency, which was particularly common during childhood and adolescence. Approximately one-third of individuals experienced progressive myopathy. Permanent muscle weakness was evident and worsened during childhood and after age 40. Those with no chronic treatment regimen have a RR of 2.3 for inadequate disease control compared to those taking long-term medications. This study revealed a multitude of heretofore unidentified characteristics of hyperPP, in addition to providing a different perspective on some previously held notions regarding the condition.

In vitro muscle contracture investigations on the malignant hyperthermia like episodes in myotonia congenita.

BACKGROUND: A common form of congenital myotonia, myotonia congenita (MC), is caused by mutations in the skeletal muscle Cl(-) channel gene type 1 (CLCN1). Due to the reduced Cl(-) conductance of the mutated channels, the patients may develop generalized muscle rigidity and hypermetabolism during general anaesthesia. The clinical symptoms resemble malignant hyperthermia (MH), which may lead to mistreatment of the patient. METHODS: Muscle specimens of ADR mice (an animal model of MC) as well as of human individuals were used and exposed to potent ryanodine receptor type 1 (RyR1) activators and increasing K(+) concentration. Muscle force was monitored by a standardized diagnostic method for MH, the so-called in vitro contracture test. RESULTS: Neither muscle of ADR mice nor MC muscle (murine and human myotonic muscle) showed pathological contractures after exposure to the potent RyR1 agonists caffeine and halothane. Increasing concentrations of K(+) had a dose-dependent preventive effect on myotonic stiffness. CONCLUSION: We conclude that the adverse anaesthetic MH-like episodes observed in MC patients do not primarily originate from an altered Ca(2+) release in skeletal muscle. In MC muscle, this hypermetabolism is facilitated by a (pharmacologically induced) sustained depolarization due to an instable membrane potential. The in vitro results suggest that these patients benefit from tight K(+) monitoring because of the membrane potential stabilizing effect of K(+) .

Permanent muscular sodium overload and persistent muscle edema in Duchenne muscular dystrophy: a possible contributor of progressive muscle degeneration.

To assess the presence and persistence of muscular edema and increased myoplasmic sodium (Na(+)) concentration in Duchenne muscular dystrophy (DMD). We examined eight DMD patients (mean age 9.5 ± 5.4 years) and eight volunteers (mean age 9.5 ± 3.2 years) with 3-tesla proton ((1)H) and (23)Na density-adapted 3D-radial MR sequences. Seven DMD patients were re-examined about 7 months later without change of therapy. The eighth DMD patient was re-examined after 5 and 11 months under medication with eplerenone. We quantified muscle edema on STIR images with background noise as reference and fatty degeneration on T1-weighted images using subcutaneous fat as reference. Na(+) was quantified by a muscular tissue Na(+) concentration (TSC) sequence employing a reference containing 51.3 mM Na(+) with 5 % agarose. With an inversion-recovery (IR) sequence, we determined mainly the myoplasmic Na(+). The normalized muscular (23)Na IR signal intensity was higher in DMD than in volunteers (n = 8, 0.75 ± 0.07 vs. 0.50 ± 0.05, p < 0.001) and persisted at second measurement (n = 7, 1st 0.75 ± 0.07, 2nd 0.73 ± 0.06, p = 0.50). When compared to volunteers (25.6 ± 2.0 mmol/l), TSC was markedly increased in DMD (38.0 ± 5.9 mmol/l, p < 0.001) and remained constant (n = 7, 1st 37.9 ± 6.4 mmol/l, 2nd 37.0 ± 4.0 mmol/l, p = 0.49). Muscular edema (15.6 ± 3.5 vs. 6.9 ± 0.7, p < 0.001) and fat content (0.48 ± 0.08 vs. 0.38 ± 0.01, p = 0.003) were elevated in DMD when compared to volunteers. This could also be confirmed during follow-up (n = 7, p = 0.91, p = 0.12). Eplerenone slightly improved muscle strength and reduced muscular sodium and edema. The permanent muscular Na(+) overload in all DMD patients is likely osmotically relevant and responsible for the persisting, mainly intracellular muscle edema that may contribute to the progressive muscle degeneration.

A novel N440K sodium channel mutation causes myotonia with exercise-induced weakness--exclusion of CLCN1 exon deletion/duplication by MLPA.

We report a 4-generation Turkish family with 10 affected members presenting with myotonia and potassium- and exercise-induced paralytic attacks. The clinical presentation was neither typical for the chloride channel myotonias Thomsen and Becker nor for the separate sodium channel myotonia entities potassium-aggravated myotonia, paramyotonia congenita, and hyperkalemic periodic paralysis. It is best described by a combination of potassium-aggravated myotonia and hyperkalemic periodic paralysis. We excluded exonic chloride channel mutations including CLCN1 exon deletion/duplication by MLPA. Instead we identified a novel p.N440K sodium channel mutation that is located at the inner end of segment S6 of repeat I. We discuss the genotype phenotype relation.

Sodium (23Na) MRI detects elevated muscular sodium concentration in Duchenne muscular dystrophy.

OBJECTIVE: In boys with Duchenne muscular dystrophy (DMD), (1)H MRI suggested muscular edema before fatty degeneration. Using specific (23)Na MRI sequences, we tested the hypothesis that the edema is caused by an osmotic effect due to increased myoplasmic Na(+) content rather than inflammation that would lead to extracellular edema. METHODS: Eleven patients with DMD (mean age, 10 ± 5 years) and 16 healthy volunteers of similar age were examined on a 3-T system with (1)H MRI and (23)Na density-adapted 3-dimensional radial MRI sequences. The muscle edema was quantified on short-tau inversion recovery images using background noise as reference. Fatty degeneration was quantified on T1-weighted images using subcutaneous fat as reference. Na(+) was quantified by a muscular tissue sodium concentration (TSC) sequence. A novel inversion recovery (IR) sequence allowed us to determine mainly the myoplasmic Na(+) by suppression of the extracellular (23)Na signal from vasogenic edema. A reference tube containing 51.3 mmol/L Na(+) with agarose gel was used for standardization. RESULTS: The normalized muscular signal intensity of (23)Na as assessed by the IR sequence was significantly higher for patients with DMD than for volunteers. TSC was markedly increased at 38.4 ± 6.8 mmol/L in patients with DMD compared with 25.4 ± 2.1 mmol/L in volunteers. The muscular edema-like changes were much more prominent in patients with DMD than in volunteers. In addition, the muscular fat content was significantly higher in patients with DMD than in volunteers. CONCLUSIONS: The elevated myoplasmic Na(+) concentration in DMD is osmotically relevant and causes a mainly intracellular muscle edema that contributes to the pathogenesis of DMD.

A randomized trial of 4-aminopyridine in EA2 and related familial episodic ataxias.

OBJECTIVE: The therapeutic effects of 4-aminopyridine (4AP) were investigated in a randomized, double-blind, crossover trial in 10 subjects with familial episodic ataxia with nystagmus. METHODS: After randomization, placebo or 4AP (5 mg 3 times daily) was administered for 2 3-month-long treatment periods separated by a 1-month-long washout period. The primary outcome measure was the number of ataxia attacks per month; the secondary outcome measures were the attack duration and patient-reported quality of life (Vestibular Disorders Activities of Daily Living Scale [VDADL]). Nonparametric tests and a random-effects model were used for statistical analysis. RESULTS: The diagnosis of episodic ataxia type 2 (EA2) was genetically confirmed in 7 subjects. Patients receiving placebo had a median monthly attack frequency of 6.50, whereas patients taking 4AP had a frequency of 1.65 (p = 0.03). Median monthly attack duration decreased from 13.65 hours with placebo to 4.45 hours with 4AP (p = 0.08). The VDADL score decreased from 6.00 to 1.50 (p = 0.02). 4AP was well-tolerated. CONCLUSIONS: This controlled trial on EA2 and familial episodic ataxia with nystagmus demonstrated that 4AP decreases attack frequency and improves quality of life. LEVEL OF EVIDENCE: This crossover study provides Class II evidence that 4AP decreases attack frequency and improves the patient-reported quality of life in patients with episodic ataxia and related familial ataxias.

[Muscle channelopathies. Myotonias and periodic paralyses]. / Muskuläre Kanalopathien. Myotonien und periodische Paralysen.

The myotonias and familial periodic paralyses are muscle channelopathies. They have in common an impaired muscle excitation that is caused by mutations in voltage-gated Na(+), K(+), Ca(2+), and Cl(-) channels. Membrane hyperexcitability usually results in myotonic stiffness; with increasing membrane depolarization hyperexcitability can be transiently turned into hypoexcitability causing transient weakness as in severe myotonia. Hypoexcitability due to long-lasting depolarization that inhibits action potential generation is the common mechanism for the periodic paralyses. Interictally, the ion channel malfunction may be compensated, so that specific exogenous or endogenous provocative factors are required to produce symptoms in the patients. An especially obvious triggering agent is the level of serum potassium, the ion decisive for resting membrane potential and degree of excitability. Periodic paralysis mutations for which the ion channel malfunction is not fully compensated interictally cause progressive myopathy.

Recovery of mechano-electrical transduction in rat cochlear hair bundles after postnatal destruction of the stereociliar cross-links.

Mechano-electrical transduction (MET) in the stereocilia of outer hair cells (OHCs) was studied in newborn Wistar rats using scanning electron microscopy to investigate the stereociliar cross-links, Nomarski laser differential interferometry to investigate stereociliar stiffness and by testing the functionality of the MET channels by recording the entry of fluorescent dye, FM1-43, into stereocilia. Preparations were taken from rats on their day of birth (P0) or 1-4 days later (P1-P4). Hair bundles developed from the base to the apex and from the inner to outer OHC rows. MET channel responses were detected in apical coil OHCs on P1. To study the possible recovery of MET after disrupting the cross-links, the same investigations were performed after the application of Ca(2+) chelator 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) and allowing the treated samples to recover in culture medium for 0-20 h. We found that the structure and function were abolished by BAPTA. In P0-P1 samples, structural recovery was complete and the open probability of MET channels reached control values. In P3-P4 samples, complete recovery only occurred in OHCs of the outermost row. Although our results demonstrate an enormous recovery potential of OHCs in the postnatal period, the structural component restricts the potential for therapy in patients.

Comparative analysis of brain structure, metabolism, and cognition in myotonic dystrophy 1 and 2.

OBJECTIVE: Myotonic dystrophy type 1 and 2 (DM1/DM2) are multisystemic diseases with common cognitive deficits beside the cardinal muscular symptoms. We performed a comprehensive analysis of cerebral abnormalities to compare the neuropsychological defects with findings in different imaging methods in the same cohort of patients. METHODS: Neuropsychological investigations, structural cerebral MRI including brain parenchymal fraction (BPF) and voxel-based morphometry (VBM), and (18)F-deoxy-glucose PET (FDG-PET) were performed in patients (20 DM1 and 9 DM2) and matched healthy controls, and analyzed using statistical parametric mapping (SPM2). RESULTS: DM1 and DM2 patients showed typical neuropsychological deficits with a pronounced impairment of nonverbal episodic memory. Both patient groups showed a reduction of the global gray matter (measured by BPF), which could be localized to the frontal and parietal lobes by VBM. Interestingly, VBM revealed a bilateral hippocampal volume reduction that was correlated specifically to both a clinical score and episodic memory deficits. VBM also revealed a pronounced change of thalamic gray matter. White matter lesions were found in >50% of patients and their extent was correlated to psychomotor speed. FDG-PET revealed a frontotemporal hypometabolism, independent of the decrease in cortical gray matter. All abnormalities were similar in both patient groups but more pronounced for DM1. CONCLUSIONS: Our results suggest that 1) some of the characteristic cognitive deficits of these patients are linked to specific structural cerebral changes, 2) decreases in gray matter and metabolism are independent processes, and 3) the widespread brain abnormalities are more pronounced in DM1.

State of the art in hereditary muscle channelopathies.

A combination of electrophysiological and genetic studies has resulted in the identification of several skeletal muscle disorders to be caused by pathologically functioning ion channels and has led to the term channelopathies. Typical hereditary muscle channelopa thies are congenital myasthenic syndromes, non-dystrophic myotonias, periodic paralyses, malignant hyperthermia, and central core disease. Most muscle channelopathies are commonly considered to be benign diseases. However, life-threatening weakness episodes or progressive permanent weakness may make these diseases severe, particularly the periodic paralyses (PP). Even in the typical PP forms characterized by episodic occurrence of weakness, up to 60% of the patients suffer from permanent weakness and myopathy with age. In addition, some PP patients present with a predominant progressive muscle weakness phenotype. The weakness can be explained by strongly depolarized fibers that take up sodium and water and that are electrically inexcitable. Drugs that repolarize the fiber membrane can restore muscle strength and may prevent progression.

Episodic ataxia type 2 showing ictal hyperhidrosis with hypothermia and interictal chronic diarrhea due to a novel CACNA1A mutation.

Autosomal dominant episodic ataxia type 2 (EA2) results from mutations of the CACNA1A gene. We describe EA2 with unusual features in a father and daughter with a novel CACNA1A mutation coding for Y248C. Both patients showed severe cerebellar atrophy in MRI and clinical signs of progressive spinocerebellar atrophy type 6. Most disabling were the very frequent episodes of ataxia with migraine (with aura in the father and without aura in the daughter) and nystagmus in our patients. Additionally, they suffered from ictal hyperhidrosis with acute hypothermia of the extremities. Lastly, the father presented with interictal chronic diarrhea not associated to a known primary gastrointestinal disorder. Both ictal hyperhidrosis and interictal diarrhea ameliorated upon acetazolamide intake, the typical treatment for EA2. The significance of these findings is discussed and the phenotype correlated to previously reported cases.

Diagnostics and therapy of muscle channelopathies--Guidelines of the Ulm Muscle Centre.

This article is dedicated to our teacher, Prof. Erich Kuhn, Heidelberg, on the occasion of his 88th birthday on 23rd November 2008. In contrast to muscular dystrophies, the muscle channelopathies, a group of diseases characterised by impaired muscle excitation or excitation-contraction coupling, can fairly well be treated with a whole series of pharmacological drugs. However, for a proper treatment proper diagnostics are essential. This article lists state-of-the-art diagnostics and therapies for the two types of myotonic dystrophies, for recessive and dominant myotonia congenita, for the sodium channel myotonias, for the primary dyskalemic periodic paralyses, for central core disease and for malignant hyperthermia susceptibility in detail. In addition, for each disorder a short summary of aetiology, symptomatology, and pathogenesis is provided.

Peripheral nerve hyperexcitability due to dominant-negative KCNQ2 mutations.

BACKGROUND: Peripheral nerve hyperexcitability (PNH) is characterized by muscle overactivity due to spontaneous discharges of lower motor neurons usually associated with antibodies against voltage-gated potassium channels. PNH may also occur in combination with episodic ataxia or epilepsy caused by mutations in K(V)1.1 or K(V)7.2 channels. Only one PNH-associated mutation has been described so far in K(V)7.2 (R207W), in a family with both PNH and neonatal seizures. METHODS: PNH was characterized by video and electromyography. The KCNQ2 gene was sequenced and K(V)7.2 channels were functionally characterized using two-microelectrode voltage-clamping in Xenopus oocytes. RESULTS: In a patient with PNH without other neurologic symptoms, we identified a novel KCNQ2 mutation predicting loss of a charged residue within the voltage sensor of K(V)7.2 (R207Q). Functional analysis of both PNH-associated mutants revealed large depolarizing shifts of the conductance-voltage relationships and marked slowing of the activation time course compared to wild type (WT) channels, less pronounced for R207Q than R207W. Co-expression of both mutant with WT channels revealed a dominant negative effect reducing the relative current amplitudes after short depolarizations by >70%. The anticonvulsant retigabine, an activator of neuronal K(V)7 channels, reversed the depolarizing shift. CONCLUSIONS: Mutations in KCNQ2 can cause idiopathic PNH alone and should be considered in sporadic cases. Both K(V)7.2 mutants produce PNH by changing voltage-dependent activation with a dominant negative effect on the WT channel. This distinguishes them from all hitherto examined Kv7.2 or K(V)7.3 mutations which cause neonatal seizures by haploinsufficiency. Retigabine may be beneficial in treating PNH.

Muscle Na+ channelopathies: MRI detects intracellular 23Na accumulation during episodic weakness.

BACKGROUND: Muscle channelopathies such as paramyotonia, hyperkalemic periodic paralysis, and potassium-aggravated myotonia are caused by gain-of-function Na+ channel mutations. METHODS: Methods: Implementation of a three-dimensional radial 23Na magnetic resonance (MR) sequence with ultra-short echo times allowed the authors to quantify changes in the total muscular 23Na signal intensity. By this technique and T2-weighted 1H MRI, the authors studied whether the affected muscles take up Na+ and water during episodes of myotonic stiffness or of cold- or exercise-induced weakness. RESULTS: A 22% increase in the 23Na signal intensity and edema-like changes on T2-weighted 1H MR images were associated with cold-induced weakness in all 10 paramyotonia patients; signal increase and weakness disappeared within 1 day. A 10% increase in 23Na, but no increase in the T2-weighted 1H signal, occurred during cold- or exercise-induced weakness in seven hyperkalemic periodic paralysis patients, and no MR changes were observed in controls or exercise-induced stiffness in six potassium-aggravated myotonia patients. Measurements on native muscle fibers revealed provocation-induced, intracellular Na+ accumulation and membrane depolarization by -41 mV for paramyotonia, by -30 mV for hyperkalemic periodic paralysis, and by -20 mV for potassium-aggravated myotonia. The combined in vivo and in vitro approach showed a close correlation between the increase in 23Na MR signal intensity and the membrane depolarization (r = 0.92). CONCLUSIONS: The increase in the total 23Na signal intensity reflects intracellular changes, the cold-induced Na+ shifts are greatest and osmotically relevant in paramyotonia patients, and even osmotically irrelevant Na+ shifts can be detected by the implemented 23Na MR technique.

A possible role of the junctional face protein JP-45 in modulating Ca2+ release in skeletal muscle.

We investigated the functional role of JP-45, a recently discovered protein of the junctional face membrane (JFM) of skeletal muscle. For this purpose, we expressed JP-45 C-terminally tagged with the fluorescent protein DsRed2 by nuclear microinjection in myotubes derived from the C2C12 skeletal muscle cell line and performed whole-cell voltage-clamp experiments. We recorded in parallel cell membrane currents and Ca(2+) signals using fura-2 during step depolarization. It was found that properties of the voltage-activated Ca(2+) current were not significantly changed in JP-45-DsRed2-expressing C2C12 myotubes whereas the amplitude of depolarization-induced Ca(2+) transient was decreased compared to control myotubes expressing only DsRed2. Converting Ca(2+) transients to Ca(2+) input flux using a model fit approach to quantify Ca(2+) removal, the change could be attributed to an alteration in voltage-activated Ca(2+) permeability rather than to altered removal properties or a lower Ca(2+) content of the sarcoplasmic reticulum (SR). Determining non-linear capacitive currents revealed a reduction of Ca(2+) permeability per voltage-sensor charge. The results may be explained by a modulatory effect of JP-45 related to its reported in vitro interaction with the dihydropyridine receptor and the SR Ca(2+) binding protein calsequestrin (CSQ).

Andersen-Tawil syndrome: new potassium channel mutations and possible phenotypic variation.

OBJECTIVE: To evaluate clinical, genetic, and electrophysiologic features of patients with Andersen-Tawil syndrome (ATS) in the United Kingdom. METHODS: Clinical and neurophysiologic evaluation was conducted of 11 families suspected to have ATS. Molecular genetic analysis of each proband was performed by direct DNA sequencing of the entire coding region of KCNJ2. Control samples were screened by direct DNA sequencing. The electrophysiologic consequences of several new mutations were studied in an oocyte expression system. RESULTS: All 11 ATS families harbored pathogenic mutations in KCNJ2 with six mutations not previously reported. Some unusual clinical features including renal tubular defect, CNS involvement, and dental and phonation abnormalities were observed. Five mutations (T75M, D78G, R82Q, L217P, and G300D) were expressed, all of which resulted in nonfunctional channels when expressed alone, and co-expression with wild-type (WT) KCNJ2 demonstrated a dominant negative effect. CONCLUSION: Six new disease-causing mutations in KCNJ2 were identified, one of which was in a PIP2 binding site. Molecular expression studies indicated that five of the mutations exerted a dominant negative effect on the wild-type allele. KCNJ2 mutations are an important cause of ATS in the UK.

Active fascial contractility: Fascia may be able to contract in a smooth muscle-like manner and thereby influence musculoskeletal dynamics.

Dense connective tissue sheets, commonly known as fascia, play an important role as force transmitters in human posture and movement regulation. Fascia is usually seen as having a passive role, transmitting mechanical tension which is generated by muscle activity or external forces. However, there is some evidence to suggest that fascia may be able to actively contract in a smooth muscle-like manner and consequently influence musculoskeletal dynamics. General support for this hypothesis came with the discovery of contractile cells in fascia, from theoretical reflections on the biological advantages of such a capacity, and from the existence of pathological fascial contractures. Further evidence to support this hypothesis is offered by in vitro studies with fascia which have been reported in the literature: the biomechanical demonstration of an autonomous contraction of the human lumbar fascia, and the pharmacological induction of temporary contractions in normal fascia from rats. If verified by future research, the existence of an active fascial contractility could have interesting implications for the understanding of musculoskeletal pathologies with an increased or decreased myofascial tonus. It may also offer new insights and a deeper understanding of treatments directed at fascia, such as manual myofascial release therapies or acupuncture. Further research to test this hypothesis is suggested.