Studies on Neuromuscular Blocking Agents and Their Antagonists During Anaesthesia

Neuromuscular blocking agents (NMBAs) are widely used in clinical anaesthesia and emergency medicine. Main objectives are to facilitate endotracheal intubation and to allow surgery by reducing muscle tone and eliminating sudden movements, which may otherwise lead to trauma and complications. The most commonly used NMBAs are non-depolarizing agents with a medium duration of action, such as rocuronium and cisatracurium. They bind to the acetylcholine receptors in the neuromuscular junction, thus inhibiting the depolarization of the postsynaptic (muscular) membrane, which is a prerequisite for muscle contraction to take place. Previously, it has been assumed that nitrous oxide (N2O), which is commonly used in combination with volatile or intravenous anaesthetics during general anaesthesia, has no effect on NMBAs. Several studies have since claimed that N2O in fact does increase the effect of NMBAs when using bolus administration of the relaxant. The effect of N2O on the infusion requirements of two NMBAs (rocuronium and cisatracurium) with completely different molecular structure and pharmacological properties was assessed. A closed-loop feedback controlled infusion of NMBA with duration of at least 90 minutes at a 90% level of neuromuscular block was used. All patients received total intravenous anaesthesia (TIVA) with propofol and remifentanil. In both studies the study group (n=35) received N2O/Oxygen and the control group (n=35) Air/Oxygen. There were no significant differences in the mean steady state infusion requirements of NMBA (rocuronium in Study I; cisatracurium in Study II) between the groups in either study. In Study III the duration of the unsafe period of recovery after reversal of rocuronium-induced neuromuscular block by using neostigmine or sugammadex as a reversal agent was analyzed. The unsafe period of recovery was defined as the time elapsed from the moment of no clinical (visual) fade in the train-of-four (TOF) sequence until an objectively measured TOF-ratio of 0.90 was achieved. The duration of these periods were 10.3 ± 5.5 and 0.3 ± 0.3 min after neostigmine and sugammadex, respectively (P < 0.001). Study IV investigated the possible effect of reversal of a rocuronium NMB by sugammadex on depth of anaesthesia as indicated by the bispectral index and entropy levels in thirty patients. Sugammadex did not affect the level of anaesthesia as determined by EEG-derived indices of anaesthetic depth such as the bispectral index and entropy.

Late-onset spinal motor neuronopathy- a new neuromuscular disease

The aim of this study was to clarify the clinical phenotype of late-onset spinal motor neuronopathy (LOSMoN), an adult-onset autosomal dominant lower motor neuron disorder identified first in two families in Eastern Finland, in order to clarify its genetic background. Motor neuron disorders (MNDs) are characterized by dysfunction and premature death of motor neurons in the brain and spinal cord. MNDs can manifest at any age of the human lifespan, ranging from pre- or neonatal forms such as spinal muscular atrophy type I (SMA I) to those preferentially affecting the older age groups exemplified by sporadic amyotrophic lateral sclerosis (ALS). With a combination of genetic linkage analysis and genome sequencing using DNA from a total of 55 affected members of 17 families and a whole genome scan, we were able to show that LOSMoN is caused by the c.197G>T p.G66V mutation in the gene CHCHD10. This study showed that LOSMoN has very characteristic features that help to differentiate it from other more malignant forms of motor neuron disease, such as ALS, which was erroneously diagnosed in many patients in our cohort. Lack of fibrillations in the first dorsal interosseus muscle on EMG and extensive grouping of non-atrophic type IIA/2A fibers on muscle biopsy were shown to be common findings in LOSMoN, but rare or absent in ALS patients. The results of this study will help clinicians recognize the characteristic phenotype of LOSMoN disease and thus improve their diagnostic accuracy, and will also allow physicians to provide adequate genetic counseling for patients.

Neck Muscle Function and Adolescent Headache

Muscular function of the neck region may be of importance for the etiology of headache, especially of tension-type headache. However, very few data exist on the association of neck muscle function with different types of headache in adolescents. The main aim of the study was to examine the association of neck muscle function with adolescent headache. The associations between leisure time activities, endurance strength of the upper extremities (UE endurance) and mobility of the neck-shoulder region and adolescent headache were studied. In addition, the associations of force production, EMG/force ratio, co-activation and fatigue characteristics, and cross-sectional area (CSA) of neck muscles with adolescent headache were studied. The study is part of a population-based cohort study of 12-year-old children with and without headache. The study had five phases (years 1998-2003). At the age of 13 years, a sample of 183 adolescents (183/311) participated in endurance strength and mobility measurements of the neck-shoulder region. In addition, the type and level of physical and other leisure activity were elicited with open and structured questions. At the age of 17 years, a random sample of 89 adolescents (89/202) participated in force and EMG measurements of the neck-shoulder muscles. In addition, at the age of 17 years, a sample of 65 adolescents (65/89) participated in CSA measurements of the neck muscles. At the age of 13 years, intensive participation in overall sports activity was associated with migraine. Frequent computer use was associated both with migraine and tension-type headache. The type of sports or other leisure activity classified them on the basis of body loading was not associated with headache type. In girls, low UE endurance of both sides, and low cervical rotation of the dominant side, were associated with tension-type headache, and low UE endurance of non-dominant side with migraine. In boys, no associations occurred between UE endurance and mobility variables and headache types. At the age of 17 years, in girls, high EMG/force ratios between the EMG of the left agonist sternocleidomastoid muscle (SCM) and maximal neck flexion and neck rotation force to the right side as well as high co-activation of right antagonist cervical erector spinae (CES) muscles during maximal neck flexion force were associated with migraine-type headache. In girls, neck force production was not associated with headache types but low left shoulder flexion force was associated with tension-type headache. In boys, no associations were found between EMG and force variables and headache. Increased SCM muscles fatigue of both sides was associated with tension-type headache. In boys, the small CSA of the right SCM muscle and, in girls, of combined right SCM and scalenus muscles was associated with tension-type headache. Similarly, in boys, the large CSA of the right SCM muscle, of the combined right SCM and scalenus muscles, of the left semispinalis capitis muscle, of the combined left semispinalis and splenius muscles was associated with migraine. No other differences in the CSA of neck flexion or extension muscles were found. Differences in the neuromucular function of the neck-shoulder muscles were associated with adolescent headache, especially in girls. Differences in the cross-sectional area of unilateral neck muscles were associated with headache, especially in boys. Differences in the neuromuscular function and in the cross-sectional area of the neck muscles also occurred between different types of headache. It remains to be established whether the findings are primary or secondary to adolescent migraine and tension headache. Keywords: adolescent, cross-sectional area, electromyography, endurance strength, fatigue, force, headache, leisure time activity, migraine, mobility, neck muscles, tension-type headache

Minkä nuorena hallitsee sen aikuisena taitaa? Liikehallinnan pysyvyys kouluiästä aikuisikään – 24 vuoden seurantatutkimus

Tässä 24 vuoden pitkittäistutkimuksessa tutkitaan liikehallinnan kehitystä ja pysyvyyttä kouluiästä aikuisikään. Lisäksi ennustetaan ja selitetään aikuisiän liikehallintaa kouluiän liikehallinnan perusteella. Tutkimukseen osallistui 44 miestä ja 44 naista eri puolilta Suomea, joiden liikehallintaa mitattiin kouluiässä 1985 ja 1988 (9–16-vuotiaina) sekä aikuisiässä 2009 (33−39-vuotiaina). Liikehallintaa mitattiin kuudella liiketehtävämittarilla (flamingoseisonta, tarkkuusheittokiinniotto, kahdeksikkokuljetus, edestakaisinhyppely, vauhditon 5-loikka ja kärrynpyörä) sekä niistä lasketulla summamuuttujalla. Miesten ja naisten liikehallintaa vertailtiin varianssianalyysilla. Kouluiässä pojat menestyivät välineenkäsittelytehtävissä ja tytöt tasapaino- ja voimistelutehtävissä, mutta kokonaisuutena sukupuolten välillä ei ollut eroa. Aikuisena miehet olivat naisia parempia lähes kaikissa tehtävissä. Kovarianssianalyysissä havaittiin, että kehonrakenteeltaan (BMI) erilaisten ryhmien liikehallinnassa oli vain yksittäisiä eroja koulu- ja aikuisiässä. Toistettujen mittausten varianssianalyysissa ilmeni, että kouluiässä molempien sukupuolten liikehallinnan kehitys oli samanlaista. Kouluiän jälkeen kevyiden ja keskipainoisten poikien liikehallinta parani, mutta painavien tulokset eivät muuttuneet. Kevyiden tyttöjen tuloksissa ei tapahtunut muutosta, mutta keskipainoisten ja painavien tulokset heikkenivät. Koululiikunnan tehostus- ja vertailuryhmien välille kouluiässä muodostuneet erot kaventuivat tai katosivat aikuisena. Kouluiän liikehallinnaltaan eritasoisten ryhmien väliset erot kaventuivat, mutta eivät poistuneet kouluiän jälkeen. Klusterianalyysissa tutkittavat jakaantuivat kouluiässä neljään liikehallintatyyppiin (yleishyvät, tasapainoiset, pallotaitajat ja yleisheikot), jotka säilyivät myös aikuisiässä, mutta niiden väliset erot kaventuivat. Ristiintaulukointi ja khiin neliö -testi osoittivat, että tasoryhmän ja liikehallinnan monipuolisuuden pysyvyys oli vahvaa kouluiästä aikuisikään. Koulu- ja aikuisiän liikehallintatulosten välinen korrelaatio oli naisilla (0.69) vahvempaa kuin miehillä (0.48). Yksittäiset mittaustulokset kouluiässä selittivät keskimäärin 33 % aikuisiän tuloksista (korrelaation neliö). Regressioanalyysissa miesten aikuisiän liikehallintaa selittivät kouluiän muuttujista parhaiten liikehallinnan monipuolisuus sekä liikkuvuus (61 %), mutta naisilla vain liikehallinnan monipuolisuus (37 %). Miesten ja naisten erot liikehallinnassa syntyivät kouluiän jälkeen, mikä johtunee erilaisista liikuntatavoista ja -harrastuksista. Kouluiän liikehallinta määritti vahvasti varsinkin tytöillä aikuisiän liikehallintaa sekä yksilö- että ryhmätasolla, mikä korostaa monipuolisen koululiikunnan merkitystä. Yksilölliset muutokset olivat mahdollisia. Kouluiän jälkeen erityisesti naiset ja kehonrakenteeltaan painavat tarvitsisivat hermolihasjärjestelmää monipuolisesti kuormittavaa ja liikesuunniltaan moniulotteista liikuntaa liikehallinnan kehittämiseksi ja ylläpitämiseksi. Naisten liikehallinnan taantuminen varsinkin tasapainotehtävissä voi altistaa kaatumistapaturmille ja rajoittaa fyysistä toimintakykyä.