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Rationale: Tetanus is usually caused by wound infection with Clostridium tetani after acute injuries. Skin cancer wound is a rarely reported cause of tetani infection. It is difficult to be diagnosed and mistaken for other brain lesions., Patient Concerns: A 49-year-old man presenting with the only symptom of repeated convulsions was admitted to our department. He had an ulcerated skin cancer on the right buttock that had been excised in another hospital 1 month before admission, leaving the wound unhealed. He was suspected of having a metastatic brain tumor early, but exhibited a negative cranial CT-scan., Diagnosis: Tetanus was diagnosed when he was observed to have sudden convulsions after sensory stimulation such as noise, light, or touch., Interventions: Despite administration of a high dose of diazepam and phenobarbitone, continuous generalized rigidity with laryngospasm still occurred. Instead, when propofol was intravenously infused, the spastic convulsion completely stopped. Tracheotomy and mechanical ventilation were performed., Outcomes: The patient gradually recovered in 2 weeks., Lessons: Tetanus is rarely infected through the wound of an ulcerated skin cancer. Early diagnosis can only be based on accurate assessment of clinical manifestations, and propofol infusion appears to be more effective in anti-convulsion management for patients with tetanus. Routine vaccination to prevent tetanus in patients with ulcerated skin cancer should be considered in the future clinical work.

Autonomic nervous system dysfunction (ANSD) is a significant cause of mortality in tetanus. Currently, diagnosis relies on nonspecific clinical signs. Heart rate variability (HRV) may indicate underlying autonomic nervous system activity and represents a potentially valuable noninvasive tool for ANSD diagnosis in tetanus. HRV was measured from three 5-minute electrocardiogram recordings during a 24-hour period in a cohort of patients with severe tetanus, all receiving mechanical ventilation. HRV measurements from all subjects-five with ANSD (Ablett Grade 4) and four patients without ANSD (Ablett Grade 3)-showed HRV was lower than reported ranges for healthy individuals. Comparing different severities of tetanus, raw data for both time and frequency measurements of HRV were reduced in those with ANSD compared with those without. Differences were statistically significant in all except root mean square SD, indicating HRV may be a valuable tool in ANSD diagnosis.

A large number of bacterial toxins consist of active and cell binding protomers linked by an interchain disulfide bridge. The largest family of such disulfide-bridged exotoxins is that of the clostridial neurotoxins that consist of two chains and comprise the tetanus neurotoxins causing tetanus and the botulinum neurotoxins causing botulism. Reduction of the interchain disulfide abolishes toxicity, and we discuss the experiments that revealed the role of this structural element in neuronal intoxication. The redox couple thioredoxin reductase-thioredoxin (TrxR-Trx) was identified as the responsible for reduction of this disulfide occurring on the cytosolic surface of synaptic vesicles. We then discuss the very relevant finding that drugs that inhibit TrxR-Trx also prevent botulism. On this basis, we propose that ebselen and PX-12, two TrxR-Trx specific drugs previously used in clinical trials in humans, satisfy all the requirements for clinical tests aiming at evaluating their capacity to effectively counteract human and animal botulism arising from intestinal toxaemias such as infant botulism., (© 2019 The Authors Cellular Microbiology Published by John Wiley & Sons Ltd.)

Background: In many countries, in-hospital survival from tetanus is increasing, but long-term outcome is unknown. In high-income settings, critical illness is associated with muscle wasting and poor functional outcome, but there are few data from resource-limited settings. In this study we aimed to assess muscle wasting and long-term functional outcome in adults with tetanus., Methods: In a prospective observational study involving 80 adults with tetanus, sequential rectus femoris ultrasound measurements were made at admission, 7 days, 14 days and hospital discharge. Functional outcome was assessed at hospital discharge using the Timed Up and Go test, Clinical Frailty Score, Barthel Index and RAND 36-item Short Form Health Survey (SF-36) and 3 and 6 months after discharge using the SF-36 and Barthel Index., Results: Significant muscle wasting occurred between hospital admission and discharge (p<0.01), particularly in severe disease, where a median 23.49% (interquartile range 10.01-26.07) reduction in rectus femoris cross-sectional area occurred in those with severe (Ablett grades 3 and 4) disease. Muscle mass at discharge was related to objective and subjective measures of physical and emotional function at discharge and 3 and 6 months after discharge. In patients >70 y of age, functional recovery at 6 months was reduced compared with younger patients. Hospital-acquired infection and age were risk factors for muscle wasting., Conclusions: Significant muscle wasting during hospitalization occurred in patients with tetanus, the extent of which correlates with functional outcome., (© The Author(s) 2019. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Approximately 20% of the nationally reported tetanus infections in children aged 0 to 14 years that occurred in the United States between 2005 and 2015 were treated at Penn State Children's Hospital. With an electronic medical record search, we identified 5 cases of pediatric tetanus; 100% of these cases occurred in unimmunized children. Their median length of stay was 10 days, and the costs were significant., (© The Author(s) 2018. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background/aims: In this study, we evaluated the functional impact of facilitatory presynaptic adenosine A2A and muscarinic M1 receptors in the recovery of neuromuscular tetanic depression caused by the blockage of high-affinity choline transporter (HChT) by hemicholinium-3 (HC-3), a condition that mimics a myasthenia-like condition., Methods: Rat diaphragm preparations were indirectly stimulated via the phrenic nerve trunk with 50-Hz frequency trains, each consisting of 500-750 supramaximal intensity pulses. The tension at the beginning (A) and at the end (B) of the tetanus was recorded and the ratio (R) B/A calculated., Results: Activation of A2A and M1 receptors with CGS21680 (CGS; 2 nmol/L) and McN-A-343c (McN; 3 μmol/L) increased R values. Similar facilitatory effects were obtained with forskolin (FSK; 3 μmol/L) and phorbol 12-myristate 13-acetate (PMA; 10 μmol/L), which activate adenylate cyclase and protein kinase C respectively. HC-3 (4 μmol/L) decreased transmitter exocytosis measured by real-time videomicroscopy with the FM4-64 fluorescent dye and prevented the facilitation of neuromuscular transmission caused by CGS, McN, and FSK, with a minor effect on PMA. The acetylcholinesterase inhibitor, neostigmine (NEO; 0.5 μmol/L), also decreased transmitter exocytosis. The paradoxical neuromuscular tetanic fade caused by NEO (0.5 μmol/L) was also prevented by HC-3 (4 μmol/L) and might result from the rundown of the positive feedback mechanism operated by neuronal nicotinic receptors (blocked by hexamethonium, 120 μmol/L)., Conclusion: Data suggest that the recovery of tetanic neuromuscular facilitation by adenosine A2A and M1 receptors is highly dependent on HChT activity and may be weakened in myasthenic patients when HChT is inoperative., (© 2018 S. Karger AG, Basel.)

Research on bacterial toxins is closely linked to the birth of immunology. Our understanding of the interaction of bacterial protein toxins with immune cells has helped to decipher immunopathology, develop preventive and curative treatments for infections, and propose anti-cancer immunotherapies. The link started when Behring and Kitasato demonstrated that serotherapy was effective against 'the strangling angel', namely diphtheria, and its dreadful toxin discovered by Roux and Yersin. The antitoxin treatment helped to save thousands of children. Glenny demonstrated the efficacy of the secondary immune response compared to the primary one. Ramon described anatoxins that allowed the elaboration of effective vaccines and discovered the use of adjuvant to boost the antibody response. Similar approaches were later made for the tetanus toxin. Studying antitoxin antibodies Ehrlich demonstrated, for the first time, the transfer of immunity from mother to newborns. In 1989 Marrack and Kappler coined the concept of 'superantigens' to characterize protein toxins that induce T-lymphocyte proliferation, and cytokine release by both T-lymphocytes and antigen presenting cells. More recently, immunotoxins have been designed to kill cancer cells targeted by either specific antibodies or cytokines. Finally, the action of IgE antibodies against toxins may explain their persistence through evolution despite their side effect in allergy.

Blood serum from immunized humans or animals (e.g., horses) contains relevant antibodies and has been used as serum therapy to treat many diseases or envenomation events. The effectiveness of blood serum was initially discovered in 1890 when Kitasato and von Behring observed the effectiveness of this type of therapy against diphtheria and tetanus. Serum therapies played an important role in the advancement of modern medicine prior to the development of penicillin and steroids. At present, several types of serum therapy remain in clinical use. However, some physicians have a limited understanding of the nature and the benefits of serum therapy and the factors that require particular attention. In this review, we set out to clarify the benefits, cautions, and potential applications of serum therapy in the context of conditions such as gas gangrene, diphtheria, botulism, and tetanus and bites from three snake species (mamushi, habu, and yamakagashi) and the redback spider. It is hoped that this review will help clinicians to learn about clinical serum therapies and become familiar with their applications.

Tetanus is a disease characterized by spastic paralysis and spasms. It is a serious pathology that requires treatment in the ICU. Mortality rate is primarily due to neurodegenerative and infectious complications. Thromboembolic complications are rare. To the best of our knowledge, pulmonary embolism has never occorred and been confirmed in patients with generalized tetanus. Our study reports the case of a patient with generalized tetanus complicated by fibrin, cruoric pulmonary embolism., Competing Interests: Les auteurs ne déclarent aucun conflit d’intérêts.

We test the hypothesis that cytosolic inorganic phosphate (P i ) can account for the contraction-induced reductions in twitch duration which impair summation and cause force to decline (sag) during unfused tetanic contractions of fast-twitch muscle. A five-state model of crossbridge cycling was used to simulate twitch and unfused tetanic contractions. As P i concentration ([P i ]) was increased from 0 to 30 mmol·L -1 , twitch duration decreased, with progressive reductions in sensitivity to P i as [P i ] was increased. When unfused tetani were simulated with rising [P i ], sag was most pronounced when initial [P i ] was low, and when the magnitude of [P i ] increase was large. Fast-twitch extensor digitorum longus (EDL) muscles (sag-prone, typically low basal [P i ]) and slow-twitch soleus muscles (sag-resistant, typically high basal [P i ]) were isolated from 14 female C57BL/6 mice. Muscles were sequentially incubated in solutions containing either glucose or pyruvate to create typical and low P i environments, respectively. Twitch duration was greater (P < 0.05) in pyruvate than glucose in both muscles. Stimuli applied at intervals approximately three times the time to peak twitch tension resulted in sag of 35.0 ± 3.7% in glucose and 50.5 ± 1.4% in pyruvate in the EDL (pyruvate > glucose; P < 0.05), and 3.9 ± 0.3% in glucose and 37.8 ± 2.7% in pyruvate in the soleus (pyruvate > glucose; P < 0.05). The influence of P i on crossbridge cycling provides a tenable mechanism for sag. Moreover, the low basal [P i ] in fast-twitch relative to slow-twitch muscle has promise as an explanation for the fiber-type dependency of sag., (© 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

A 1-week-old infant was brought to a regional hospital with a history of recurrent seizures following lower abdominal septic skin infection. She was found to have neonatal tetanus, and a spatula test was positive. The tetanus infection was associated with a superficial skin infection, common in neonates. Treatment included sedatives (diazepam, chlorpromazine, phenobarbitone and morphine), muscle relaxants, antibiotics and ventilation in the neonatal intensive care unit. Intrathecal and intramuscular immunoglobulin were given, and the wound was treated. The infant recovered, with no seizures by the 16th day from admission, and was off the ventilator by the 18th day. This was shorter than the usual 3 - 4 weeks for neonates with tetanus at the hospital. The question arises whether tetanus immunisation should be considered in infants with skin infections, which frequently occur in the neonatal period.

Despite clear consensus and strong recommendations, vaccination rates of kidney transplant (KT) recipients have remained below targets. As vaccination is most effective if it is given prior to transplantation and the initiation of immunosuppression, patients should ideally have their vaccination status assessed and optimized in the pre-transplant period. We performed a retrospective chart review to characterize vaccination rates and factors associated with gaps in vaccination in a single-center population of waitlisted patients being evaluated for kidney transplantation. We evaluated 362 KT patients. Three-quarters were receiving dialysis at the time of evaluation. Immunization rates were low with 35.9% of patients having completed vaccination for Pneumococcus, 55% for influenza, 6.9% for zoster, and 2.5% for tetanus. On multivariable analysis, patients who received other vaccines, including influenza, tetanus, or zoster vaccine (odds ratio [OR] 10.55, 95% confidence interval [CI] 5.65-19.71) were more likely to receive pneumococcal vaccine. Blacks (OR 0.24, 95% CI 0.12-0.47) were less likely to receive pneumococcal vaccine compared to whites. Patients on dialysis, and those active on the waiting list were more likely to receive pneumococcal vaccine than other groups (OR 2.81, 95% CI 1.44-5.51, and OR 1.84, 95% CI 1.08-3.14, respectively). We found that the overall immunization rate against common vaccine-preventable infections was low among patients evaluated for kidney transplantation. A significant gap remains between recommendations and vaccine uptake in clinical practice among this high-risk population., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Tetanus is a preventable infectious disease caused by tetanus toxin (tetanospasmin) produced by Clostridium tetani. Tetanus is still an important health problem in low- and middle-income countries (LMICs). Botulinum toxin administration is a treatment approach that has been used in recent years to reduce rigidity and spasms in tetanus patients. This case report focuses on its efficacy., (© The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Two cases of focal tetanus in the cat are described. Clinical findings included severe muscular spasms of the pelvic limbs in one cat, and involvement of the thoracic limbs and muscles of the neck and face in the other. Electromyography in both cats showed spontaneous activity characterised by the presence of motor unit potentials. F waves, never previously reported in focal tetanus in animals, showed significantly increased F/M amplitude ratio in both cats and increased F wave duration in one cat. The electrodiagnostic findings provided relevant diagnostic and, possibly, prognostic information.

Access to critical care is rapidly growing in areas of the world where it was previously nonexistent and where infectious diseases often comprise the largest disease burden. Additionally, with crowding, mass migrations, and air travel, infectious diseases previously geographically confined are quickly spread across the planet, often in shorter time frames than disease incubation periods. Hence, critical care practitioners must be familiar with infectious diseases previously confined to the developing world. This article reviews selected tropical diseases that are seen in diverse locales and often require critical care services., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Tetanus toxin, the product of Clostridium tetani, is the cause of tetanus symptoms. Tetanus toxin is taken up into terminals of lower motor neurons and transported axonally to the spinal cord and/or brainstem. Here the toxin moves trans-synaptically into inhibitory nerve terminals, where vesicular release of inhibitory neurotransmitters becomes blocked, leading to disinhibition of lower motor neurons. Muscle rigidity and spasms ensue, often manifesting as trismus/lockjaw, dysphagia, opistotonus, or rigidity and spasms of respiratory, laryngeal, and abdominal muscles, which may cause respiratory failure. Botulinum toxin, in contrast, largely remains in lower motor neuron terminals, inhibiting acetylcholine release and muscle activity. Therefore, botulinum toxin may reduce tetanus symptoms. Trismus may be treated with botulinum toxin injections into the masseter and temporalis muscles. This should probably be done early in the course of tetanus to reduce the risk of pulmonary aspiration, involuntary tongue biting, anorexia and dental caries. Other muscle groups are also amenable to botulinum toxin treatment. Six tetanus patients have been successfully treated with botulinum toxin A. This review discusses the use of botulinum toxin for tetanus in the context of the pathophysiology, symptomatology, and medical treatment of Clostridium tetani infection.

Background: Tetanus is now a rare disease in the Western world, but not so in developing countries. Cephalic tetanus, unlike some other local forms of the disease, is likely to be fatal., Methods: We describe the clinical presentation of a case of fatal cephalic tetanus complicating an unattended open non-severe head injury with a review of the literature on the disease., Results: Few cases of cephalic tetanus complicating head injury are found in the world literature, and many were diagnosed late. Cephalic tetanus from open or compound depressed skull fracture is even more rare. Our patient was a young male with an uncertain tetanus immunization history who sustained mild head injury (scalp laceration) and an unattended open depressed skull fracture in a motorcycle crash. He developed cephalic tetanus seven days later, presented late to our service, and died while being prepared for surgical debridement of his cranial wounds. At the immediate post-trauma medical contact, in an across-the-street "clinic," he had received suboptimal care for his head wound and inadequate tetanus prophylaxis., Conclusion: Cephalic tetanus is a rare form of the disease. Although it is preventable easily by well-established medical and surgical treatment paradigms, it continues to catch many clinicians disastrously unaware.

Background: Tetanus is an infection that can be associated with a high mortality especially in developing countries. Critical care which may include artificial control of respiration is crucial in survival, but cardiovascular complications from autonomic instability remains an important cause of death. The objective of this report is to highlight this important cause of mortality despite artificial control of ventilation to prevent respiratory arrest., Method: The medical record of the patient and relevant literature were reviewed., Result: A 29-year old male following a wound on the lower limb presented with clinical features suggestive of tetanus. Incubation period was short and immunization history was uncertain. Basic treatment directed at removing source of infection and neutralisation of unbound toxin was however commenced. Following signs of imminent respiratory failure due to severe uncontrollable spasms, controlled mechanical ventilation was instituted in the critical care unit (CCU). However, the patient succumbed to cardiac arrest as a result of severe autonomic instability, despite aggressive cardiopulmonary resuscitation., Conclusion: Cardiovascular arrest from severe autonomic instability remains an important cause of mortality in tetanus despite artificial ventilation. Early management with appropriate therapy is advisable to prevent its occurrence.

A 79 year old farmer was referred to the University Hospital with a three days history of difficulty in opening his mouth. On examination, both masseters were seen to be stiff, suggesting tetanus or jaw-subluxation. An attempt to reduce the joint was made, but failed. He subsequently developed progressive respiratory difficulties requiring intubation. The farmer had recently cut his finger on barbed wire. He had not received tetanus immunization for years and it was not clear whether primary immunization had been completed. Tetanus immunoglobulin and antibiotics were administered. He proceeded to develop autonomic instability and critical illness polyneuropathy requiring 45 days of ICU care. He was finally discharged eight months later. The farmer has gradually improved and is now living unaided at home. In this article we will review this case and the literature on tetanus.

Two men developed severe tetanus after the 2010 Haitian earthquake. They were admitted to the United States Naval Ship Comfort, a hospital ship sent to provide humanitarian relief. Severe masseter and intercostal muscle spasm impaired airway access and ventilation. Propofol and sevoflurane relieved the tetany, allowing airway control and ventilation without intubation or neuromuscular blocking drugs during wound debridement. Presynaptic impairment of inhibitory neurotransmitter release by tetanospasmin toxin is countered by enhancement of spinal cord postsynaptic inhibitory receptor activity by general anesthetics. Avoidance of tracheal intubation and mechanical ventilation during anesthesia may be desirable in the settings of limited resources in which tetanus usually presents.

The characterisation of oral-motor movements and speech of patients with tetanus were investigated to determine the existence of possible signs that are characteristic of this pathology. Thirteen patients clinically diagnosed with tetanus (10 with severe tetanus and three with very severe tetanus) and admitted to an intensive care unit underwent clinical evaluation of oral-motor movements and speech. Statistical analysis indicated significant between-group differences for speech motor functions, suggesting that individuals with very severe tetanus present rigidity as a characteristic interfering in articulatory precision (P = 0·035) and movement rate (P = 0·038). For lip closure, tongue movement, palatal elevation, gag reflex and voice quality, no between-group differences were identified for the specific abnormal characteristics. The observed abnormal results indicate that muscle strength and functional status of the oral-motor system presented by most of the participants of the study did not ensure the necessary integrity for satisfactory performance. The characterisation of the oral myofunctional aspects of patients with tetanus provides medical teams, patients and families with a wider and better description of the clinical situation, giving support to the diagnosis, prognostics and treatment., (© 2010 Blackwell Publishing Ltd.)

Tetanus is rare in a country with a national vaccination program. When it does occur, the associated autonomic dysfunction is a challenge for physicians. We report here a case of an unvaccinated 5-year-old boy who suffered from tetanus complicated by autonomic dysfunction, which was successfully controlled by the infusion of magnesium sulfate. This is the first case that demonstrated the therapeutic effect of magnesium sulfate in a child with tetanus. This case highlights the importance of implementing a vaccination program., (Copyright © 2011. Published by Elsevier B.V.)

Neonatal tetanus (NNT) remains among the leading causes of morbidity and mortality in Nigeria and a huge challenge in achieving the fourth goal of the Millennium Development Goals. We reviewed the morbidity and mortality pattern among neonates with NNT admitted to the District General Hospital in north-east Nigeria from 2006 to 2009. Half of the patients were from rural areas and were delivered at home by untrained traditional birth attendants with no prior antenatal health care. Razor blades and scissors were the instruments used to cut the cord in nonhygienic conditions. Spasticity, lack of sucking, trismus, fever, omphalitis, risus sardonicus and opisthotonus were the most common presenting signs and symptoms. Overall, mortality was 56%. Health education of mothers and traditional birth attendants, the promotion of hospital delivery and antenatal tetanus immunization of all pregnant women, particularly in rural areas, are recommended if NNT is to be prevented.

Neuromyotonia, or Isaac's syndrome, is a rare neuromuscular disorder of peripheral nerve hyperexcitability characterized by muscle stiffness, muscle hypertrophy, pseudomyotonia, myokymia and electromyographic evidence of myokymic or neuromyotonic discharges. A young boy with neuromyotonia is presented who was diagnosed with tetanus for severe muscle spasms, trismus and ophisthotonos. We discuss differentiation of neuromyotonia from tetanus and other disorders with similar features on clinical and electrophysiological examination., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Tetanus is a deadly disease of warm blooded animals and humans caused by an exotoxin called tetanospasmin or tetanus neurotoxin (TeNT) produced by anaerobic bacterium named Clostridium tetani TeNT is an A-B toxin; each molecule consists of a heavy chain (HC) containing cellular receptor binding domain and a light chain (LC) with zinc metalloprotease activity. TeNT produced in the infected tissue by the bacteria grown under anaerobic condition binds to ganglioside receptors of peripheral nerve, and endocytosed. The A subunit exits from the endosome and undergoes a retrograde transport via the nerve axon to the spinal cord. This highly toxic enzyme specifically cleaves one of the nerve cell SNARE proteins, i.e., synaptobrevin, resulting in inhibition of the release of neurotransmitters (glycine and GABA) from inhibitory interneuron causing spastic paralysis, the characteristic of tetanus. Current treatment mainstay of human tetanus is by passively administering anti-tetanus toxin produced from animals immunized with adjuvanted tetanus toxoid (TT). There are several obstacles in production and use of the animal derived therapeutic antibody especially the allergic reaction and serum sickness induced by the host immune response to the foreign protein. The animal antibody, mainly IgG, blocks nerve cell entry of the TeNT but does not neutralize the TeNT protease activity per se and cannot reverse the tetanus symptoms. In this study, fully human single chain antibody fragments (HuScFv) were produced from a human antibody phage display library. TT was used as antigen in a single round phage bio-panning to select phage clones that display TT bound-HuScFv from the library. HuScFv from 4 selected huscfv-phagemid transformed E. coli clones inhibited binding of the native TeNT to retinoic acid pulsed human neuroblastoma cells when used at the molecular TeNT:HuScFv ratio of 1:100. HuScFv from one of the 4 clones also inhibited the TeNT mediated cleavage of recombinant synaptobrevin. Further investigation is needed for identification of epitope specificity of these HuScFv and HuScFv effector mechanisms towards the TeNT. Cell penetrating version of the HuScFv that inhibited the TeNT zinc metalloprotease activity should be made. The HuScFv produced in this study either singly or in their suitable combination warrant developing further to a real use in humans as a surrogate of the animal antibody for treatment of tetanus.

Cross-bridges properties were measured under different experimental conditions by applying fast stretches to activated skeletal frog muscle fiber to -forcibly detach the cross-bridge ensemble. This allowed to measure the tension needed to detach the cross-bridges, P(c), and the sarcomere elongation at the rupture force, L(c). These two parameters are expected to be correlated with cross-bridges number (P(c)) and their mean extension (L(c)). Conditions investigated were: tetanus rise and plateau under normal Ringer and Ringer containing different BDM -concentrations, hyper (1.4T) and hypotonic (0.8T) solutions, 5 and 14 degrees C temperature. P(c) was linearly correlated with the tension (P) developed by the fibers under all the conditions examined, however the ratio P(c)/P changed depending on conditions being greater at low temperature and higher tonicity. These results indicate that, (a) P(c) can be used as a measure of attached cross-bridge number and (b) the force developed by the individual cross-bridge increases at high temperature and low tonicity. L(c) was not affected by tension developed, however it changed under different conditions, being greater at low temperature and high tonicity. These findings, suggests, in agreement with P(c) data, that cross-bridge extension is smaller at low temperature and high tonicity. By comparing these data with tetanic tension we concluded that potentiation or depression induced on tetanic force by tonicity or temperature changes are entirely accounted for by changes of the force developed by the individual cross-bridge.

Domoic acid (DOM) is known to cause hippocampal neuronal damage and produces amnesic effects. We examined synaptic plasticity changes induced by DOM exposure in rat hippocampal CA1 region. Brief bath application of DOM to hippocampal slices produces a chemical form of long-term potentiation (LTP) of CA1 field synaptic potentials. The potentiation cannot be blocked by NMDA receptor antagonist MK-801 but can be blocked by the calcium-calmodulin-dependent protein kinase II (CaMKII) inhibitor KN-62 or cAMP-dependent protein kinase (PKA) inhibitor H-89. DOM-potentiated slices show decreased autophosphorylated CaMKII (p-Thr286), an effect that is also dependent on the activity of CaMKII and PKA. Increased phosphorylation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor subunit GluR1 (p-Ser831) was seen in DOM-potentiated slices. Therefore, aberrant regulation of CaMKII and GluR1 phosphorylation occurs after DOM application. In addition, tetanus-induced LTP as well as the increase of phosphorylation of CaMKII (p-Thr286) were reduced in DOM-potentiated slices. Compared with brief exposure, slices recovering from prolonged exposure did not show potentiation or altered levels of CaMKII (p-Thr286) or GluR (p-Ser831). However, decreased phosphorylation of GluR1 at Ser845 was seen. These results describe a new chemical form of LTP and uncover novel molecular changes induced by DOM. The observed impairment of tetanus LTP and misregulation of CaMKII and GluR1 phosphorylation may partially account for DOM neurotoxicity and underlie the molecular basis for DOM-induced memory deficit.

Purpose: Few anesthesiologists have expertise in the diagnosis and treatment of tetanus, a disease that remains prevalent in developing countries. We report on a series of four cases of tetanus cases recently encountered in Rwanda. We review the clinical epidemiology, pathophysiology, diagnosis and the treatment of tetanus, and provide implications for anesthesiologists and critical care physicians., Clinical Features: We report four cases, two involving adults who were inadequately vaccinated and experienced injuries, and two involving neonates, both of whom underwent umbilical cord transection using unsterilized equipment. All patients required tracheal intubation, and were mechanically ventilated when equipment was available. One adult and one neonate succumbed to the disease. These cases highlight the difficulties of diagnosis and management of complicated diseases in the resource-challenged health care setting of developing countries., Conclusions: The differential diagnosis of tetanus may be confusing, and survival depends on the rapidity of treatment with antitoxin, as well as adequate supportive care. High doses of sedatives and muscle relaxants, as well as prolonged mechanical ventilation, are usually necessary. Mortality remains high, usually resulting from late respiratory failure and cardiovascular collapse, associated with autonomic instability. Anesthesiologists and critical care physicians have an important role to play in the management of these patients. Increased involvement in humanitarian health organizations, immigration from developing countries, and emergence of high risk groups in developed countries will likely result in more exposure of anesthesiologists to the complexities of this disease.

We report a 7-year-old boy with very severe tetanus treated with continuous infusion of magnesium sulphate for the control of spasms and severe autonomic dysfunction which was refractory to deep sedation and mechanical ventilation. The infusion was not associated with any adverse effects and he made an uneventful recovery. We recommend the use of intravenous magnesium sulphate infusion as an inexpensive and highly effective modality in severe tetanus.

Tetanus is endemic in many developing countries. Although propofol has been proposed for sedation in tetanus, the routine use of this drug has not been clearly documented in published reports. A few studies have reported its beneficial effects but no randomized studies are available. We describe the case of a five-year-old boy who presented with severe tetanus in East Africa. The antispastic therapy consisted of benzodiazepine infusion with the addition of titrated boluses of propofol. Intubation and mechanical ventilation were avoided.

This review summarizes the microbiology, management and prevention of tetanus. Tetanus is an acute toxemic illness caused by Clostridium tetani infection at a laceration or break in the skin. It can also occur as a complication of burns, puerperal infections, umbilical stumps (tetanus neonatorum) and surgical-site infection. Tetanus is an intoxication, manifested mostly by neuromuscular dysfunction, caused by tetanal exotoxin (tetanospasmin), a potent exotoxin produced by C. tetani. It starts with tonic spasms of the skeletal muscles and is followed by paroxysmal contractions. The muscle stiffness initially involves the jaw (lockjaw) and neck and later becomes generalized. Treatment goals include interrupting the production of toxin, neutralizating the unbound toxin, controlling muscle spasms, managing dysautonomia and appropriate supportive management. Specific therapy includes intramuscular administration of tetanus immunoglobulin to neutralize circulating toxin before it binds to neuronal cell membranes. The disease can be prevented by immunization with tetanal toxoid and appropriate wound care.

Purpose: To examine force generation and duration of effect of botulinum toxin pretreatment, followed by injection of ricin-mAb35 in extraocular muscle., Methods: In normal adult rabbits, one superior rectus muscle was injected with either 5 units botulinum toxin or 1/50 maximally tolerated dose for rats (rMTD) of ricin-mAb35. Additional rabbits were first injected with 5 units botulinum toxin, and after 1, 2, or 4 weeks the same muscle was injected with either 1/10 or 1/50 rMTD ricin-mAb35. In each treatment group, the contralateral muscle was injected with an equal volume of saline. After 12 weeks (1/50 rMTD) or 6 months (1/10 rMTD), the rabbits were euthanized. Both SR muscles were removed and assayed physiologically, using an in vitro apparatus., Results: Twelve weeks after treatment with either botulinum toxin or immunotoxin alone, only ricin-mAb35-treated muscles were weaker than control muscles at tetanic stimulation frequencies. Pretreatment with botulinum toxin prior to injection with immunotoxin, especially at shorter intervals between injections, resulted in significant decreases in twitch and tetanic force generation compared with controls and muscles treated with ricin-mAb35 only or botulinum toxin only. At 6 months, force generation was decreased from control only in muscles treated with the higher dose of ricin-mAb35. Botulinum toxin pretreatment did not augment this effect at 6 months., Conclusions: Upregulation of postsynaptic nicotinic acetylcholine receptors caused by botulinum toxin pretreatment amplifies the reduction of force generation in extraocular muscle following secondary injection of the immunotoxin ricin-mAb35 within 3 months of treatment.

Maternal and neonatal tetanus are important causes of maternal and neonatal mortality, claiming about 180 000 lives worldwide every year, almost exclusively in developing countries. Although easily prevented by maternal immunisation with tetanus toxoid vaccine, and aseptic obstetric and postnatal umbilical-cord care practices, maternal and neonatal tetanus persist as public-health problems in 48 countries, mainly in Asia and Africa. Survival of tetanus patients has improved substantially for those treated in hospitals with modern intensive-care facilities; however, such facilities are often unavailable where the tetanus burden is highest. The Maternal and Neonatal Tetanus Elimination Initiative assists countries in which maternal and neonatal tetanus has not been eliminated to provide immunisation with tetanus toxoid to women of childbearing age. The ultimate goal of this initiative is the worldwide elimination of maternal and neonatal tetanus. Since tetanus spores cannot be removed from the environment, sustaining elimination will require improvements to presently inadequate immunisation and health-service infrastructures, and universal access to those services. The renewed worldwide commitment to the reduction of maternal and child mortality, if translated into effective action, could help to provide the systemic changes needed for long-term elimination of maternal and neonatal tetanus.

We report a case of 11 years old male who developed trismus associated with left infranuclear facial palsy following injury over forehead. Cephalic tetanus was diagnosed. Rarity of the case as well as mild course it ran, though the incubation period was less than seven days, is the reason for this case report.

The case records of 20 dogs that were treated for tetanus between 1988 and 2004 were reviewed. Young, large-breed dogs were most commonly affected. Twelve dogs had a likely source of infection identified. All dogs were treated with intravenous antibiotics and supportive care, such as muscle relaxants and sedation for muscle tremors and rigidity. Sixteen dogs received tetanus antitoxin. The mortality rate was 50%. Complete recovery in survivors required approximately 1 month.

As a result of the advances in the control of pulmonary insufficiency in tetanus, the cardiovascular system has increasingly been shown to be a determining factor in morbidity and mortality but detailed knowledge of the cardiovascular complications in tetanus is scanty. The 24h-Holter was carried out in order to detect arrhythmias and sympathetic overactivity in 38 tetanus patients admitted to an ICU. The SDNN Index (standard deviation from the normal R-to-R intervals), was useful in detecting adrenergic tonus, and ranged from 64.1 +/- 27 in the more severe forms of tetanus to 125 +/- 69 in the milder ones. Sympathetic overactivity occurred in 86.2% of the more severe forms of the disease, but was also detected in 33% of the milder forms. Half the patients had their sympathetic overactivity detected only by the Holter. The most frequent arrhythmias were isolated supraventricular (55.2%) and ventricular (39.4%) extrasystoles. There was no association of the arrhythmias with the clinical form of tetanus or with the presence of sympathetic overactivity. The present study demonstrated that major cardiovascular dysfunction, particularly sympathetic overactivity, occurs in all forms of tetanus, even in the milder ones. This has not been effectively detected with traditional monitoring in ICU and may not be properly treated.

Background: The most common cause of death in individuals with severe tetanus in the absence of mechanical ventilation is spasm-related respiratory failure, whereas in ventilated patients it is tetanus-associated autonomic dysfunction. Our aim was to determine whether continuous magnesium sulphate infusion reduces the need for mechanical ventilation and improves control of muscle spasms and autonomic instability., Methods: We did a randomised, double blind, placebo controlled trial in 256 Vietnamese patients over age 15 years with severe tetanus admitted to the Hospital for Tropical Medicine, Ho Chi Minh City, Vietnam. Participants were randomly assigned magnesium sulphate (n=97) or placebo solution (n=98) intravenously for 7 days. The primary outcomes were requirement of assisted ventilation and of drugs to control muscle spasms and cardiovascular instability within the 7-day study period. Analyses were done by intention to treat. This trial is registered as an International Standard Randomised Clinical Trial, number ISRCTN74651862., Findings: No patients were lost to follow-up. There was no difference in requirement for mechanical ventilation between individuals treated with magnesium and those receiving placebo (odds ratio 0.71, 95% CI 0.36-1.40; p=0.324); survival was also much the same in the two groups. However, compared with the placebo group, patients receiving magnesium required significantly less midazolam (7.1 mg/kg per day [0.1-47.9] vs 1.4 mg/kg per day [0.0-17.3]; p=0.026) and pipecuronium (2.3 mg/kg per day [0.0-33.0] vs 0.0 mg/kg per day [0.0-14.8]; p=0.005) to control muscle spasms and associated tachycardia. Individuals receiving magnesium were 4.7 (1.4-15.9) times less likely to require verapamil to treat cardiovascular instability than those in the placebo group. The incidence of adverse events was not different between the groups., Interpretation: Magnesium infusion does not reduce the need for mechanical ventilation in adults with severe tetanus but does reduce the requirement for other drugs to control muscle spasms and cardiovascular instability.

Introduction: Autonomic disturbances in tetanus are traditionally associated with adrenergic variations and/or cardiac dysfunction, based on case report data. The objective of this study was to measure catecholamines, (TNF)-alpha and troponin T relative to and left ventricular ejection fraction (LVEF) in patients with severe tetanus., Methods: This prospective study was carried out at two general Intensive Care Units and included 21 patients consecutively admitted with severe tetanus. Catecholamines (dopamine, norepinephrine, epinephrine and total catecholamines), tumor necrosis factor (TNF)-alpha and LVEF were assessed during the first week of autonomic instability and following tetanus recovery. Troponin T was measured during autonomic instability only., Results: Mean age of patients was 46 +/- 17 years, median Acute Physiology and Chronic Health Evaluation II (APACHE II) score was 8 (range 1-23). All patients had both blood pressure and heart rate instability. Two patients were recuperated from cardiac arrest. Intensive Care Unit mortality was 14% (3 cases). No increase in total catecholamines or in TNF-alpha levels was observed during autonomic instability or in the recovery period. Six patients had troponin T > 0.01 ng/ml and six had > 0.1 ng/ml. Mean LVEF was similar during autonomic instability and after tetanus recovery, 67 +/- 7% and 65 +/- 7%, respectively. Troponin T levels correlated with pressoric instability during autonomic instability., Conclusion: Our study demonstrated that in patients with severe tetanus no significant increased levels of catecholamines or TNF-alpha or evidence of cardiac systolic dysfunction was observed either during autonomic instability or in the recovery period. Elevated values of troponin T detected during autonomic instability were not associated with left ventricular dysfunction. Our data do not support the hypothesis that autonomic disturbances in tetanus are associated with adrenergic variations or cardiac dysfunction.

Patients with tetanus complaining of common signs such as lockjaw, voice disturbance, and difficulty in swallowing, etc, should never be forgotten. A 71-year old woman complained of dyspnea and difficulty in swallowing. She had lockjaw with tongue bite soon after a tracheostomy, and she was diagnosed as having tetanus. She showed the redundant gag reflex even to a slight stimulus and limited mobility of bilateral vocal cords, which improved following intravenous administration of diazepam. This case suggests that the mobility of the vocal cords and the movement of the larynx could be limited in tetanus because even a slight stimulus caused a strong gag reflex, resulting in dyspnea or difficulty in swallowing.

Tetanus is characterized by tetanic convulsions related to the actions of tetanospasmin produced by Clostridium tetani. Another important characteristic of tetanus is the instability of the cardiovascular system related to sympathetic hyperactivity in the autonomic nervous system, and it may be an important prognostic factor. We report a patient with tetanus in whose unstable circulatory kinetics made circulation management difficult. A 77-year-old woman who injured in a fall, 11 days after trismus appeared and 3 day after convulsion appeared. It was not severe case in the acuity classification. However, repeated generalized convulsions and autonomic imbalance involving the cardiovascular system were observed clinically, suggesting a severe case. Because of the unstable circulatory kinetics, the patient was carefully managed was performed in the intensive care unit (ICU), and she improved. ICU management may be essential for treating severe tetanus with cardiovascular complications. Acquired immunity is not achieved after the onset of tetanus, and since elderly people, in particular, as in our own caset, are easily injured when they fall, we recommend vaccination.

Background: This review covers the pathogenesis and treatment of the disease along with the reexamination of the current recommendations for prophylaxis against tetanus in the United States. Although tetanus is still a major problem worldwide, the incidence in North America has become almost negligible because of the highly effective primary immunization program. Recently, there have been no deaths reported attributable to tetanus in the United States in trauma patients who had received the primary childhood immunization. However, tetanus immunization and prophylaxis in the acute injury setting is frequently misused and misunderstood., Methods: A review of the literature regarding tetanus., Results: After review, the authors recommend tetanus toxoid in adults only if it has been more than 10 years since their last immunization. There is no urgency for the administration of tetanus toxoid in the acute setting, as it provides protection against the next injury and not the current injury. Tetanus-diphtheria toxoid is not required unless there are plans for the injured patient to travel to diphtheria-prone countries in the future, as the incidence of diphtheria is negligible in the United States., Conclusion: The review of reported cases of tetanus demonstrates that it is not possible to clinically determine which wounds are tetanus prone, as tetanus can occur after minor, seemingly innocuous injuries, yet is rare after severely contaminated wounds. Tetanus immunoglobulin should be reserved for patients with wounds who had never received primary immunization against tetanus.

Movement disorders may present acutely, and failure to recognize and exclude important differential diagnoses can result in significant morbidity or mortality. Unfortunately, much of the literature pertaining to this topic is scattered and not easily accessible. This review aims to address this deficit. Movement disorder emergencies are discussed according to their most likely mode of presentation. Diagnostic considerations and early management principles are reviewed, along with appropriate pathophysiology where relevant., (2004 Movement Disorder Society.)