-
The Journal of Pharmacology and... Nov 2019In December 2018, the Centers for Disease Control declared fentanyl the deadliest drug in America. Opioid overdose is the single greatest cause of death in the United... (Review)
Review
In December 2018, the Centers for Disease Control declared fentanyl the deadliest drug in America. Opioid overdose is the single greatest cause of death in the United States adult population (ages 18-50), and fentanyl and its analogs [fentanyl/fentanyl analogs (F/FAs)] are currently involved in >50% of these deaths. Anesthesiologists in the United States were introduced to fentanyl in the early 1970s when it revolutionized surgical anesthesia by combining profound analgesia with hemodynamic stability. However, they quickly had to master its unique side effect. F/FAs can produce profound rigidity in the diaphragm, chest wall and upper airway within an extremely narrow dosing range. This clinical effect was called wooden chest syndrome (WCS) by anesthesiologists and is not commonly known outside of anesthesiology or to clinicians or researchers in addiction research/medicine. WCS is almost routinely fatal without expert airway management. This review provides relevant clinical human pharmacology and animal data demonstrating that the significant increase in the number of F/FA-induced deaths may involve -adrenergic and cholinergic receptor-mediated mechanical failure of the respiratory and cardiovascular systems with rapid development of rigidity and airway closure. Although morphine and its prodrug, heroin, can cause mild rigidity in abdominal muscles at high doses, neither presents with the distinct and rapid respiratory failure seen with F/FA-induced WCS, separating F/FA overdose from the slower onset of respiratory depression caused by morphine-derived alkaloids. This distinction has significant consequences for the design and implementation of new pharmacologic strategies to effectively prevent F/FA-induced death. SIGNIFICANCE STATEMENT: Deaths from fentanyl and F/FAs are increasing in spite of availability and awareness of the opioid reversal drug naloxone. This article reviews literature suggesting that naloxone may be ineffective against centrally mediated noradrenergic and cholinergic effects of F/FAs, which clinically manifest as severe muscle rigidity and airway compromise (e.g., wooden chest syndrome) that is rapid and distinct from respiratory depression seen with morphine-derived alkaloids. A physiologic model is proposed and implications for new drug development and treatment are discussed.
Topics: Adrenergic Neurons; Analgesics, Opioid; Drug Overdose; Fentanyl; Humans; Muscle Rigidity; Naloxone; Narcotic Antagonists; Opioid Epidemic; Respiratory Insufficiency; Time-to-Treatment
PubMed: 31492824
DOI: 10.1124/jpet.119.258566 -
Journal of Neurology, Neurosurgery, and... Feb 1993
Review
Topics: Humans; Muscle Cramp; Muscle Rigidity; Muscles; Osteochondrodysplasias; Peripheral Nerves; Spasm; Spinal Cord; Stiff-Person Syndrome
PubMed: 8436998
DOI: 10.1136/jnnp.56.2.121 -
Neuroscience Bulletin Feb 2012Parkinson's disease (PD) is a chronic progressive neurodegenerative disease that is clinically manifested by a triad of cardinal motor symptoms - rigidity, bradykinesia... (Review)
Review
Parkinson's disease (PD) is a chronic progressive neurodegenerative disease that is clinically manifested by a triad of cardinal motor symptoms - rigidity, bradykinesia and tremor - due to loss of dopaminergic neurons. The motor symptoms of PD become progressively worse as the disease advances. PD is also a heterogeneous disease since rigidity and bradykinesia are the major complaints in some patients whereas tremor is predominant in others. In recent years, many studies have investigated the progression of the hallmark symptoms over time, and the cardinal motor symptoms have different rates of progression, with the disease usually progressing faster in patients with rigidity and bradykinesia than in those with predominant tremor. The current treatment regime of dopamine-replacement therapy improves motor symptoms and alleviates disability. Increasing the dosage of dopaminergic medication is commonly used to combat the worsening symptoms. However, the drug-induced involuntary body movements and motor complications can significantly contribute to overall disability. Further, none of the currently-available therapies can slow or halt the disease progression. Significant research efforts have been directed towards developing neuroprotective or disease-modifying agents that are intended to slow the progression. In this article, the most recent clinical studies investigating disease progression and current progress on the development of disease-modifying drug trials are reviewed.
Topics: Animals; Disease Progression; Dopaminergic Neurons; Humans; Hypokinesia; Movement; Muscle Rigidity; Parkinson Disease; Tremor
PubMed: 22233888
DOI: 10.1007/s12264-012-1050-z -
Toxins Jan 2013Tetanus 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... (Review)
Review
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.
Topics: Animals; Botulinum Toxins, Type A; Humans; Models, Animal; Neuromuscular Agents; Spasm; Tetanus; Trismus
PubMed: 23299659
DOI: 10.3390/toxins5010073 -
Frontiers in Neuroscience 2016Parkinson disease (PD) is a chronic and progressive movement disorder classically characterized by slowed voluntary movements, resting tremor, muscle rigidity, and... (Review)
Review
Parkinson disease (PD) is a chronic and progressive movement disorder classically characterized by slowed voluntary movements, resting tremor, muscle rigidity, and impaired gait and balance. Medical treatment is highly successful early on, though the majority of people experience significant complications in later stages. In advanced PD, when medications no longer adequately control motor symptoms, deep brain stimulation (DBS) offers a powerful therapeutic alternative. DBS involves the surgical implantation of one or more electrodes into specific areas of the brain, which modulate or disrupt abnormal patterns of neural signaling within the targeted region. Outcomes are often dramatic following DBS, with improvements in motor function and reductions motor complications having been repeatedly demonstrated. Given such robust responses, emerging indications for DBS are being investigated. In parallel with expansions of therapeutic scope, advancements within the areas of neurosurgical technique and the precision of stimulation delivery have recently broadened as well. This review focuses on the revolutionary addition of DBS to the therapeutic armamentarium for PD, and summarizes the technological advancements in the areas of neuroimaging and biomedical engineering intended to improve targeting, programming, and overall management.
PubMed: 27199637
DOI: 10.3389/fnins.2016.00173 -
Medicina (Kaunas, Lithuania) 2002The neuroleptic malignant syndrome (NMS) is a rare but potentially lethal form of neuroleptic drug-induced hyperthermia, altered level of consciousness, extrapyramidal... (Review)
Review
The neuroleptic malignant syndrome (NMS) is a rare but potentially lethal form of neuroleptic drug-induced hyperthermia, altered level of consciousness, extrapyramidal effects, autonomic instability and muscle rigidity. The present review describes pathophysiology, frequency, course, outcome, mortality and management of NMS in prehospital care and emergency department care. Review discusses clinical features, diagnosis differentiation of this hyperpyretic-rigidity syndrome from other disorders and prevention of this serious iatrogenic condition as life-threatening disorder.
Topics: Acute Kidney Injury; Adult; Amantadine; Bromocriptine; Carbidopa; Contraindications; Dantrolene; Diagnosis, Differential; Dopamine Agents; Dopamine Agonists; Female; Humans; Intensive Care Units; Levodopa; Male; Muscle Relaxants, Central; Neuroleptic Malignant Syndrome; Prognosis; Rhabdomyolysis
PubMed: 12474710
DOI: No ID Found -
Postgraduate Medical Journal Sep 2001Hyperekplexia (startle disease) is a rare non-epileptic disorder characterised by an exaggerated persistent startle reaction to unexpected auditory, somatosensory and... (Review)
Review
Hyperekplexia (startle disease) is a rare non-epileptic disorder characterised by an exaggerated persistent startle reaction to unexpected auditory, somatosensory and visual stimuli, generalised muscular rigidity, and nocturnal myoclonus. The genetic basis is a mutation usually of the arginine residue 271 leading to neuronal hyperexcitability by impairing glycinergic inhibition. Hyperekplexia is usually familial, most often autosomal dominant with complete penetrance and variable expression. It can present in fetal life as abnormal intrauterine movements, or later at any time from the neonatal period to adulthood. Early manifestations include abnormal responses to unexpected auditory, visual, and somatosensory stimuli such as sustained tonic spasm, exaggerated startle response, and fetal posture with clenched fists and anxious stare. The tonic spasms may mimic generalised tonic seizures, leading to apnoea and death. Consistent generalised flexor spasm in response to tapping of the nasal bridge (without habituation) is the clinical hallmark of hyperekplexia. Electroencephalography may show fast spikes initially during the tonic spasms, followed by slowing of background activity with eventual flattening corresponding to the phase of apnoea bradycardia and cyanosis. Electromyography shows a characteristic almost permanent muscular activity with periods of electrical quietness. Nerve conduction velocity is normal. No specific computed tomography findings have been reported yet. Clonazepam, a gamma aminobutyric acid (GABA) receptor agonist, is the treatment of choice for hypertonia and apnoeic episodes. It, however, may not influence the degree of stiffness significantly. A simple manoeuvre like forced flexion of the head and legs towards the trunk is known to be life saving when prolonged stiffness impedes respiration.
Topics: Diagnosis, Differential; Humans; Infant, Newborn; Muscle Rigidity; Reflex, Abnormal; Reflex, Startle
PubMed: 11524514
DOI: 10.1136/pmj.77.911.570 -
European Journal of Neurology Oct 2018Antibodies to glycine receptors (GlyR-Abs) were first defined in progressive encephalopathy with rigidity and myoclonus (PERM) but were subsequently identified in other... (Review)
Review
BACKGROUND AND PURPOSE
Antibodies to glycine receptors (GlyR-Abs) were first defined in progressive encephalopathy with rigidity and myoclonus (PERM) but were subsequently identified in other clinical presentations. Our aim was to assess the clinical associations of all patients identified with GlyR-Abs in Queensland, Australia, between April 2014 and May 2017 and to compare these to cases reported in the literature.
METHODS
A literature review identified the clinical features of all published GlyR-Ab-positive cases through online databases. A case series was undertaken via collection of clinical information from all patients diagnosed or known to immunology, pathology or neurological services in Queensland during the study period of 3 years.
RESULTS
In all, 187 GlyR-Ab-positive cases were identified in the literature. The majority (47.6%) had PERM, 22.4% had epilepsy, but the remaining 30% included mixed phenotypes consisting of cerebellar ataxia, movement disorders, demyelination and encephalitis/cognitive dysfunction. By contrast, in our series of 14 cases, eight had clinical presentations consistent with seizures and epilepsy and only three cases had classical features of PERM. There was one case each of global fatiguable weakness with sustained clonus, laryngeal dystonia and movement disorder with hemiballismus and tics. The rate of response to immune therapy was similar in all groups.
CONCLUSION
Antibodies to glycine receptors are linked to a spectrum of neurological disease. The results of the literature review and our case series suggest a greater relationship between GlyR-Abs and epilepsy than previously reported.
Topics: Adolescent; Adult; Aged; Australia; Autoantibodies; Child; Child, Preschool; Encephalitis; Female; Humans; Infant; Male; Middle Aged; Movement Disorders; Muscle Rigidity; Myoclonus; Phenotype; Receptors, Glycine; Young Adult
PubMed: 29904974
DOI: 10.1111/ene.13721 -
Journal of Physical Therapy Science Nov 2019[Purpose] We investigated the occurrence of delayed-onset muscle soreness and the suppression of muscle rigidity by ultrasound irradiation before high-load exercise....
[Purpose] We investigated the occurrence of delayed-onset muscle soreness and the suppression of muscle rigidity by ultrasound irradiation before high-load exercise. [Participants and Methods] The study was a randomized crossover controlled trial. The participants were 28 healthy university students (12 males, 16 females). Delayed-onset muscle soreness was induced in the biceps brachii muscle; ultrasound (3 MHz, 1.5 W/cm, 10 min) was applied before high-load exercise. Pain during elbow motion was evaluated on a visual analog scale. Muscle rigidity was evaluated using a muscle rigidity meter. [Results] After exercise on the second day, the ultrasound group showed significantly less muscle rigidity. [Conclusion] The heat stimulus of ultrasound therapy before high-load exercise reduces muscle rigidity.
PubMed: 31871378
DOI: 10.1589/jpts.31.922 -
Journal of Neurology, Neurosurgery, and... Jun 1994Three patients with antibiotic induced meningitis, one following penicillin with seven episodes, are reported on--the first well documented description of penicillin... (Review)
Review
Three patients with antibiotic induced meningitis, one following penicillin with seven episodes, are reported on--the first well documented description of penicillin induced meningitis. In this patient episodes of headache and nuchal rigidity appeared with and without CSF pleocytosis. Two patients had a total of five episodes of antibiotic induced meningitis after trimethoprim-sulphamethoxazole (co-trimoxazole) administration. The features common to all three patients were myalgia, confusion and low CSF glucose. CSF analysis was not a reliable method to differentiate antibiotic induced meningitis from partially treated bacterial meningitis.
Topics: Adolescent; Aged; Aged, 80 and over; Cerebrospinal Fluid; Confusion; Diagnosis, Differential; Female; Glucose; Headache; Humans; Male; Meningitis; Muscle Rigidity; Neck Muscles; Penicillins; Recurrence; Trimethoprim, Sulfamethoxazole Drug Combination
PubMed: 8006651
DOI: 10.1136/jnnp.57.6.705