Nově vzniklá svalová slabost kriticky nemocných (ICUAW) je častou komplikací intenzivní péče s dalekosáhlým dopadem, především na její dlouhodobý výsledek. ICUAW je asociována se syndromem systémové zánětlivé odpovědi (SIRS) a lze na ni nahlížet jako na projev multiorgánové dysfunkce na úrovni periferního nervu a svalu. Na úrovni periferního nervu dochází k hyperpolarizaci membrány a poruše vedení vzruchu díky snížení počtu a změně vlastností Na+ kanálů. Ve svalových vláknech je porušena fluk - tuace intracelulární koncentrace Ca2+ v průběhu cyklu kontrakce-relaxace. Snižuje se též obsah kontraktilních bílkovin (proteolýza), jader (apoptóza) i mitochondrií, které jsou funkčně defektní (bioenergetické selhání). Postižení svalu u kriticky nemocného tedy zahrnuje jak funkční defekt (myopatii), tak úbytek tkáně (sarkopenii). Klinická diagnostika ICUAW je v podmínkách JIP/ARO obtížná a často opožděná, přesné určení podílu postižení nervové a svalové tkáně na svalové slabosti má spíše akademický význam, neboť specifickou terapii v současnosti neznáme. Prevence a terapie je individualizovaná a spočívá v minimalizaci vyvolávajících faktorů, adekvátní nutrici (prevence sarkopenie) a co nejčasnější mobilizaci kriticky nemocného.

Intensive Care Unit-Acquired Weakness (ICUAW) is a common complication of intensive care that places significant impact on the long-term outcome. ICUAW is associated with systemic inflammatory response syndrome (SIRS) and is now considered an aspect of the multiple-organ failure syndrome at the level of peri - pheral nerves and muscles. The membrane of the peripheral nerve is hyperpolarized and is inexcitable at least in part due to the changes of both the number and features of the Na+ channels. Within the muscles, the intracellular Ca2+ fluctuation pattern flattens during the cycle of contraction-relaxation. There is also a decrease in the contractile protein content, and in the reduction of the number of both the nuclei and mitochondria. Thus, the muscle involvement in ICUAW includes both functional changes (myopathy) and a net loss of muscle tissue (sarcopenia). The diagnosis of ICUAW is difficult and often delayed. Direct assessment of the extent to which the muscles and nerves contribute to weakness is often not worthy, as no specific therapy is yet available. The prevention and management of ICUAW now consist of avoiding risk factors, providing adequate nutrition and encouraging the culture of early mobilization of ICU patients.

• Keywords
• SIRS, polyneuromyopatie,
• MeSH
• Critical Illness therapy   MeSH
• Humans MeSH
• Neuromuscular Diseases etiology   prevention & control   therapy   MeSH
• Critical Care methods   MeSH
• Sarcopenia physiopathology   prevention & control   MeSH
• Muscle Weakness diagnosis   physiopathology   prevention & control   MeSH
• Muscles physiopathology   pathology   MeSH
• Systemic Inflammatory Response Syndrome complications   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

Funkční poruchy hybnosti jsou významným zdrojem disability. Diagnóza funkčních poruch hybnosti je založená na průkazu inkonzistence hybných projevů a na inkompatibilitě s jiným organickým onemocněním, a nikoliv na vyloučení jiného onemocnění či průkazu psychopatologie. Role neurologa spočívá v předání pozitivní diagnózy a vysvětlení, že funkční symptomy jsou skutečné, časté a potenciálně reverzibilní, a také v dlouhodobém sledování vývoje neurologických příznaků. Narůstající evidence svědčí pro účinnost fyzioterapie a psychoterapeutických intervencí buď samostatně, nebo v kombinaci. Úkolem psychiatrů je diagnostika a léčba psychiatrických komorbidit, zejména úzkosti a deprese. Farmakologické intervence cílené na motorické symptomy nejsou indikované.

Functional movement disorders are important source of disability. Diagnosis of functional movement disorders should be based on positive signs of inconsistency of motor symptoms and their incompatibility with an organic disorder and not on exclusion of other conditions. The role of neurologist involves the delivery of a positive diagnosis and an explanation that functional symptoms are genuine, common, and potentially reversible, and a long-term follow-up. Increasing evidence supports the efficacy of physiotherapy and psychotherapy alone or in combination. Psychiatrists should evaluate and treat psychiatric comorbidities such as anxiety and/or depression. Pharmacological treatments directed at motor symptoms are not appropriate.

• Keywords
• funkční poruchy pohybu, Hooverovo znamení, funkční slabost,
• MeSH
• Humans MeSH
• Motor Disorders * diagnosis   physiopathology   therapy   MeSH
• Movement Disorders * diagnosis   physiopathology   therapy   MeSH
• Muscle Weakness * diagnosis   physiopathology   therapy   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

BACKGROUND: Mitochondrial damage occurs in the acute phase of critical illness, followed by activation of mitochondrial biogenesis in survivors. It has been hypothesized that bioenergetics failure of skeletal muscle may contribute to the development of ICU-acquired weakness. The aim of the present study was to determine whether mitochondrial dysfunction persists until protracted phase of critical illness. METHODS: In this single-centre controlled-cohort ex vivo proof-of-concept pilot study, we obtained vastus lateralis biopsies from ventilated patients with ICU-acquired weakness (n = 8) and from age and sex-matched metabolically healthy controls (n = 8). Mitochondrial functional indices were measured in cytosolic context by high-resolution respirometry in tissue homogenates, activities of respiratory complexes by spectrophotometry and individual functional capacities were correlated with concentrations of electron transport chain key subunits from respiratory complexes II, III, IV and V measured by western blot. RESULTS: The ability of aerobic ATP synthesis (OXPHOS) was reduced to ~54% in ICU patients (p<0.01), in correlation with the depletion of complexes III (~38% of control, p = 0.02) and IV (~26% of controls, p<0.01) and without signs of mitochondrial uncoupling. When mitochondrial functional indices were adjusted to citrate synthase activity, OXPHOS and the activity of complexes I and IV were not different, whilst the activities of complexes II and III were increased in ICU patients 3-fold (p<0.01) respectively 2-fold (p<0.01). CONCLUSIONS: Compared to healthy controls, in ICU patients we have demonstrated a ~50% reduction of the ability of skeletal muscle to synthetize ATP in mitochondria. We found a depletion of complex III and IV concentrations and relative increases in functional capacities of complex II and glycerol-3-phosphate dehydrogenase/complex III.

• MeSH
• Adenosine Triphosphate metabolism   physiology   MeSH
• Organelle Biogenesis MeSH
• Quadriceps Muscle metabolism   MeSH
• Energy Metabolism physiology   MeSH
• Glycerolphosphate Dehydrogenase metabolism   MeSH
• Intensive Care Units MeSH
• Cohort Studies MeSH
• Muscle, Skeletal metabolism   MeSH
• Critical Illness MeSH
• Middle Aged MeSH
• Humans MeSH
• Mitochondria metabolism   pathology   MeSH
• Oxidative Stress physiology   MeSH
• Pilot Projects MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Muscle Weakness etiology   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Obstructive sleep apnoea syndrome (OSAS) is a common disorder associated with upper airway muscle dysfunction. Agents that improve respiratory muscle performance may have considerable therapeutic value. We examined the effects of acute exposure to sustained and intermittent hypoxia on rat pharyngeal dilator muscle function. Additionally, we sought to test the efficacy of antioxidant treatment in ameliorating or preventing hypoxia-related muscle dysfunction. Isometric contractile and endurance properties of isolated rat sternohyoid muscle bundles were examined at 35 °C in vitro. Muscle bundles were exposed to one of four gas treatments: hyperoxia (control), sustained hypoxia (SH), intermittent hypoxia (IH) or hypoxia/re-oxygenation (HR), in the absence or presence of the superoxide scavenger--Tempol (10 mM). Stress-frequency relationship was determined in response to electrical stimulation (10-100 Hz in increments of 10-20 Hz, train duration: 300 ms). Muscle performance was also assessed during repetitive muscle stimulation (40 Hz, 300 ms every 2 s for 2.5 min). Compared to control, IH and HR treatments significantly decreased sternohyoid muscle force. The negative inotropic effect of the two gas protocols was similar, but both were of lesser magnitude than the effects of SH. SH, but not IH and HR, increased muscle fatigue. Tempol significantly increased sensitivity to stimulation in all muscle preparations and caused a leftward shift in the stress-frequency relationship of IH and SH treated muscles. Tempol did not ameliorate sternohyoid muscle fatigue during SH. We conclude that Tempol increases upper airway muscle sensitivity to stimulation but only modestly ameliorates respiratory muscle weakness during intermittent and sustained hypoxic conditions in vitro. Respiratory muscle fatigue during sustained hypoxia appears unrelated to oxidative stress.

• MeSH
• Cyclic N-Oxides therapeutic use   MeSH
• Respiratory Muscles physiopathology   MeSH
• Hypoxia physiopathology   MeSH
• Data Interpretation, Statistical MeSH
• Isometric Contraction drug effects   MeSH
• Rats MeSH
• Rats, Wistar MeSH
• Free Radical Scavengers therapeutic use   MeSH
• Spin Labels MeSH
• Superoxides metabolism   MeSH
• Muscle Weakness physiopathology   MeSH
• In Vitro Techniques MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Funkční (psychogenní) poruchy hybnosti jsou v ambulancích neurologů časté. Jejich patofyziologie je ovšem stále málo známa a také v klinických názorech na jejich dia­gnostiku a léčbu dosud existuje řada nejasností. Klinicky jsou funkční poruchy hybnosti charakterizovány především měnlivými a obvykle nestálými příznaky, které se neshodují s typickými projevy hybné poruchy způsobené organickým neurologickým onemocněním. V tomto přehledu uvádíme terminologii, definice, výskyt a typické projevy funkčních poruch hybnosti i jejich jednotlivých forem a dia­gnostická klinická kritéria. Dále přinášíme nové poznatky o jejich patofyziologii, které zpochybňují v minulosti zdůrazňovanou kauzální roli psychických faktorů a nasvědčují neurobio­logickému modelu vzniku příznaků. Dia­gnóza funkčních poruch hybnosti by měla spočívat na nálezu charakteristických klinických projevů a nikoliv pouze na vyloučení organických příčin. Z hlediska prognózy je rozhodující časné stanovení dia­gnózy a její přijetí pacientem. Léčebné postupy zahrnují multimodální přístup s dominantní úlohou neurologa, jenž stanovuje a sděluje dia­gnózu a řídí léčebný postup.

Functional (psychogenic) movement disorders are frequently seen in neurology outpatient clinics. However, the underlying pathophysiology is still poorly understood and from the clinical perspective, there can be many uncertainties regarding their diagnosis and treatment. Functional movement disorders are clinically characterized by variability and inconsistency of symptoms that are incongruent with movement disorders known to be caused by an organic neurological disease. Here we review the terminology, definitions, epidemiology and typical presentations of functional movement disorders and their individual forms and clinical dia­gnostic criteria. Furthermore, we review advances in our knowledge of the pathophysiology that question the formerly emphasized causal role of psychological factors, and proposes a neurobiological model of the symptom development. Diagnosis of functional movement disorders should be based on the presence of characteristic clinical features and not on exclusion of an organic cause only. Early diagnosis and its acceptance by the patient are crucial for the prognosis. Management of functional movement disorders involves a multimodal approach with a dominant role of a neurologist, who establishes and communicates the diagnosis and determines treatment. Key words: functional movement disorders – psychogenic movement disorders – inconsistency – incongruence – Hoover test The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manu­script met the ICMJE “uniform requirements” for biomedical papers.

• Keywords
• psychogenní poruchy hybnosti, Hooverův test, inkongruence, inkonzistence,
• MeSH
• Medical History Taking methods   MeSH
• Chorea diagnosis   etiology   physiopathology   MeSH
• Gait MeSH
• Diagnostic Techniques, Neurological MeSH
• Diagnosis, Differential MeSH
• Dystonia diagnosis   etiology   physiopathology   MeSH
• Conversion Disorder diagnosis   etiology   MeSH
• Humans MeSH
• Myoclonus diagnosis   etiology   physiopathology   MeSH
• Parkinsonian Disorders diagnosis   etiology   physiopathology   MeSH
• Movement Disorders * diagnosis   etiology   physiopathology   therapy   MeSH
• Signs and Symptoms MeSH
• Psychotherapy methods   MeSH
• Somatoform Disorders * diagnosis   etiology   physiopathology   therapy   MeSH
• Muscle Weakness diagnosis   etiology   physiopathology   MeSH
• Physical Therapy Modalities MeSH
• Terminology as Topic MeSH
• Tremor diagnosis   etiology   physiopathology   MeSH
• Symptom Assessment MeSH
• Physician-Patient Relations MeSH
• Check Tag
• Humans MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH

Skeletal muscle is a highly adaptable organ, and its amount declines under catabolic conditions such as critical illness. Aging is accompanied by a gradual loss of muscle, especially when physical activity decreases. Intensive care unit-acquired weakness is a common and highly serious neuromuscular complication in critically ill patients. It is a consequence of critical illness and is characterized by a systemic inflammatory response, leading to metabolic stress, that causes the development of multiple organ dysfunction. Muscle dysfunction is an important component of this syndrome, and the degree of catabolism corresponds to the severity of the condition. The population of critically ill is aging; thus, we face another negative effect-sarcopenia-the age-related decline of skeletal muscle mass and function. Low-grade inflammation gradually accumulates over time, inhibits proteosynthesis, worsens anabolic resistance, and increases insulin resistance. The cumulative consequence is a gradual decline in muscle recovery and muscle mass. The clinical manifestation for both of the above conditions is skeletal muscle weakness, with macromolecular damage, and a common mechanism-mitochondrial dysfunction. In this review, we compare the molecular mechanisms underlying the two types of muscle atrophy, and address questions regarding possible shared molecular mechanisms, and whether critical illness accelerates the aging process.

• MeSH
• Intensive Care Units MeSH
• Muscle, Skeletal MeSH
• Critical Illness MeSH
• Humans MeSH
• Muscular Diseases * complications   MeSH
• Sarcopenia * complications   MeSH
• Muscular Atrophy complications   MeSH
• Muscle Weakness etiology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

Deficit transportu riboflavinu (RTD), známý také jako Brown-Vialetto-van Laere syndrom, je vzácné onemocnění, které na základě poruchy oxidativního metabolizmu vede k úbytku neuronů v jádrech hlavových i periferních nervů. Projevy jsou ztráta svalové síly, ptóza očního víčka, bulbární syndrom a respirační potíže doprovázené těžkou postsynaptickou sluchovou neuropatií. Je-li projeven v dětském věku, vede k úmrtí pro respirační selhání v řádu měsíců až let. Na prezentovaném případu familiárního výskytu u sourozenců je demonstrována nutnost rychlého zahájení substituční léčby riboflavinem, která může předejít rozvoji onemocnění nebo alespoň zmírnit jeho projevy a zvýšit šanci na úspěšnou rehabilitaci sluchu. Při záchytu sluchové neuropatie u dětí doporučujeme vyšetření multigenového NGS/MPS panelu, který zahrnuje i vzácnější příčiny vrozené poruchy sluchu. V případě výskytu jakéhokoli dalšího příznaku onemocnění je třeba neprodleně zahájit substituční léčbu.

Riboflavin transporter deficiency (RTD) is rare disease characterized by progressive loss of cranial and somatic nerve function. Typically ptosis, bulbar syndrome, muscle weakness, and auditory neuropathy are manifested. Without treatment, this leads to death caused by respiratory failure, especially when it starts in childhood. In this paper, we present two siblings with RTD and demonstrate the necessity of early diagnosis and riboflavin substitution treatment. Riboflavin substitution can prevent hearing loss and increase the chance for successful hearing rehabilitation. Comparison with other existing literature is given. We recommend to test every child with captured auditory neuropathy spectrum disorder for a multi-gene NGS/MPS panel and provide substitution treatment before genetic test results, especially when other symptoms are manifested.

• MeSH
• Child MeSH
• Genetic Testing MeSH
• Cochlear Implants MeSH
• Infant MeSH
• Humans MeSH
• Riboflavin Deficiency * diagnosis   genetics   therapy   MeSH
• Hearing Disorders etiology   therapy   MeSH
• Riboflavin therapeutic use   MeSH
• Family MeSH
• Check Tag
• Child MeSH
• Infant MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Case Reports MeSH
• Review MeSH

BACKGROUND: Intensive care unit (ICU)-acquired weakness is the most important cause of failed functional outcome in survivors of critical care. Most damage occurs during the first week when patients are not cooperative enough with conventional rehabilitation. Functional electrical stimulation-assisted cycle ergometry (FES-CE) applied within 48 h of ICU admission may improve muscle function and long-term outcome. METHODS: An assessor-blinded, pragmatic, single-centre randomized controlled trial will be performed. Adults (n = 150) mechanically ventilated for < 48 h from four ICUs who are estimated to need > 7 days of critical care will be randomized (1:1) to receive either standard of care or FES-CE-based intensified rehabilitation, which will continue until ICU discharge. PRIMARY OUTCOME: quality of life measured by 36-Item Short Form Health Survey score at 6 months. SECONDARY OUTCOMES: functional performance at ICU discharge, muscle mass (vastus ultrasound, N-balance) and function (Medical Research Council score, insulin sensitivity). In a subgroup (n = 30) we will assess insulin sensitivity and perform skeletal muscle biopsies to look at mitochondrial function, fibre typing and regulatory protein expression. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02864745. Registered on 12 August 2016.

• MeSH
• Time Factors MeSH
• Bicycling * MeSH
• Electric Stimulation Therapy * adverse effects   MeSH
• Ergometry * MeSH
• Intensive Care Units MeSH
• Muscle, Skeletal innervation   MeSH
• Critical Illness MeSH
• Quality of Life MeSH
• Humans MeSH
• Recovery of Function MeSH
• Pragmatic Clinical Trials as Topic MeSH
• Muscle Contraction * MeSH
• Muscle Strength * MeSH
• Muscle Weakness diagnosis   physiopathology   rehabilitation   MeSH
• Treatment Outcome MeSH
• Exercise Test MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial Protocol MeSH
• Geographicals
• Czech Republic MeSH

BACKGROUND: Functional mitochondria in skeletal muscle of patients with protracted critical illness and intensive care unit-acquired weakness are depleted, but remaining mitochondria have increased functional capacities of respiratory complexes II and III. This can be an adaptation to relative abundancy of fatty acid over glucose caused by insulin resistance. We hypothesized that the capacity of muscle mitochondria to oxidize fatty acid is increased in protracted critical illness. METHODS: We assessed fatty acid oxidation (FAO) and mitochondrial functional indices in vitro by using extracellular flux analysis in cultured myotubes obtained by isolating and culturing satellite cells from vastus lateralis muscle biopsy samples from patients with ICU-acquired weakness (n = 6) and age-matched healthy controls (n = 7). Bioenergetic measurements were performed at baseline and after 6 days of exposure to free fatty acids (FFAs). RESULTS: Mitochondrial density in myotubes from ICU patients was 69% of healthy controls ( P = .051). After adjustment to mitochondrial content, there were no differences in adenosine triphosphate (ATP) synthesis or the capacity and coupling of the respiratory chain. FAO capacity in ICU patients was 157% of FAO capacity in controls ( P = .015). In myotubes of ICU patients, unlike healthy controls, the exposure to FFA significantly ( P = .009) increased maximum respiratory chain capacity. CONCLUSION: In an in vitro model of skeletal muscle of patients with protracted critical illness, we have shown signs of adaptation to increased FAO. Even in the presence of glucose and insulin, elevation of FFAs in the extracellular environment increased maximal capacity of the respiratory chain.

• MeSH
• Quadriceps Muscle MeSH
• Energy Metabolism * MeSH
• Adaptation, Physiological MeSH
• Insulin blood   MeSH
• Insulin Resistance MeSH
• Intensive Care Units * MeSH
• Muscle Fibers, Skeletal MeSH
• Muscle, Skeletal cytology   physiopathology   MeSH
• Blood Glucose metabolism   MeSH
• Critical Illness * MeSH
• Fatty Acids, Nonesterified metabolism   MeSH
• Middle Aged MeSH
• Humans MeSH
• Lipolysis MeSH
• Electron Transport Complex II metabolism   MeSH
• Aged MeSH
• Muscle Weakness etiology   metabolism   physiopathology   MeSH
• Mitochondria, Muscle physiology   MeSH
• Electron Transport MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

PURPOSE: Functional electrical stimulation-assisted cycle ergometry (FESCE) enables in-bed leg exercise independently of patients' volition. We hypothesised that early use of FESCE-based progressive mobility programme improves physical function in survivors of critical care after 6 months. METHODS: We enrolled mechanically ventilated adults estimated to need >7 days of intensive care unit (ICU) stay into an assessor-blinded single centre randomised controlled trial to receive either FESCE-based protocolised or standard rehabilitation that continued up to day 28 or ICU discharge. RESULTS: We randomised in 1:1 ratio 150 patients (age 61±15 years, Acute Physiology and Chronic Health Evaluation II 21±7) at a median of 21 (IQR 19-43) hours after admission to ICU. Mean rehabilitation duration of rehabilitation delivered to intervention versus control group was 82 (IQR 66-97) versus 53 (IQR 50-57) min per treatment day, p<0.001. At 6 months 42 (56%) and 46 (61%) patients in interventional and control groups, respectively, were alive and available to follow-up (81.5% of prespecified sample size). Their Physical Component Summary of SF-36 (primary outcome) was not different at 6 months (50 (IQR 21-69) vs 49 (IQR 26-77); p=0.26). At ICU discharge, there were no differences in the ICU length of stay, functional performance, rectus femoris cross-sectional diameter or muscle power despite the daily nitrogen balance was being 0.6 (95% CI 0.2 to 1.0; p=0.004) gN/m2 less negative in the intervention group. CONCLUSION: Early delivery of FESCE-based protocolised rehabilitation to ICU patients does not improve physical functioning at 6 months in survivors. TRIAL REGISTRATION NUMBER: NCT02864745.

• MeSH
• Time Factors MeSH
• Electric Stimulation MeSH
• Ergometry methods   MeSH
• Intensive Care Units * MeSH
• Critical Illness rehabilitation   MeSH
• Quality of Life * MeSH
• Middle Aged MeSH
• Humans MeSH
• Follow-Up Studies MeSH
• Prospective Studies MeSH
• Muscle Strength physiology   MeSH
• Muscle Weakness physiopathology   rehabilitation   MeSH
• Exercise Therapy methods   MeSH
• Respiration, Artificial methods   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Randomized Controlled Trial MeSH