Materiały źródłowe

• #1 Paralysis | Causes, Symptoms & Treatment | Britannica

  https://www.britannica.com/science/paralysis

  paralysis, loss or impairment of voluntary muscular movement caused by structural abnormalities of nervous or muscular tissue or by metabolic disturbances in neuromuscular function. […] Most diseases that cause paralysis can be divided into two main groups depending on whether they entail structural alterations in nervous or muscular tissue, or lead to metabolic disturbances in neuromuscular function. […] The most common cause of hemiplegia is damage to the corticospinal tracts and associated motor tracts in one hemisphere of the brain from obstruction (blood clot or thrombosis) or rupture (cerebral hemorrhage) of a major cerebral artery. […] Bilateral hemiplegia with pseudobulbar palsy results from diffuse, bilateral brain diseases such as occurs in severe cerebral arteriosclerosis or cerebral vascular syphilis.

• #2 Paralysis: What It Is, Causes, Symptoms, Management & Types

  https://my.clevelandclinic.org/health/diseases/15345-paralysis

  Paralysis occurs when you’re unable to make voluntary muscle movements. A nervous system problem causes paralysis. Nerves send signals to your muscles. Those signals make your muscles move. When you’re paralyzed, or have paralysis, you can’t move certain parts of your body. […] A problem with your nervous system causes paralysis. Your nervous system is your body’s command and communication system. It sends signals from your brain throughout your body, telling it what to do. If something damages your nervous system, messages can’t get through to your muscles. […] Most often, a traumatic injury or medical condition damages muscle and nerve function. Strokes and spinal cord injuries are the most common causes of paralysis. Other causes include: Birth defects like spina bifida. Autoimmune diseases, including multiple sclerosis (MS) and Guillain-Barr syndrome. Brain injuries, including conditions like traumatic brain injury and cerebral palsy. Neurological diseases, like amyotrophic lateral sclerosis (ALS).

• #3 Muscular Weakness (Paresis and Paralysis) – Signs and Symptoms – McMaster Textbook of Internal Medicine

  https://empendium.com/mcmtextbook/chapter/B31.I.1.21.

  Muscular weakness is one of the most common neurologic presentations. […] Paresis is a reduction in muscle strength with a limited range of voluntary movement. Paralysis (-plegia) is a complete inability to perform any movement. […] Dysfunction may be of the upper motor neurons (cerebral motor cortex, subcortical structures, brainstem, and corticospinal tracts) or lower motor neurons (motor nuclei of the cranial nerves or motor neurons of the ventral horn of the spinal cord; or peripheral nerve, muscle, or neuromuscular junction). […] Spastic weakness: Upper motor neuron dysfunction. Commonly caused by stroke (ischemic or hemorrhagic), mass lesions (tumor, abscess), demyelination, or trauma. […] Flaccid weakness: Lower motor neuron dysfunction. Caused by neuropathy (Guillain-Barr syndrome, heavy metal poisoning, adverse effects of drugs [vincristine, isoniazid], neuropathy in patients with autoimmune diseases or diabetes, acute intermittent porphyria, nerve compression, critical illness myopathy, critical illness neuropathy), neuromuscular junction disorders (myasthenia gravis, botulism, effects of muscle relaxants, organophosphate poisoning), or muscle disorders (inflammatory myopathy: polymyositis, inclusion body myositis, dermatomyositis), muscular dystrophy, electrolyte abnormalities (among others, periodic paralysis in patients with hypokalemia or hyperkalemia, hypomagnesemia, hypercalcemia).

• #4 Muscular Weakness (Paresis and Paralysis) – Signs and Symptoms – McMaster Textbook of Internal Medicine

  https://empendium.com/mcmtextbook/chapter/B31.I.1.21.

  Muscular weakness is one of the most common neurologic presentations. […] Paresis is a reduction in muscle strength with a limited range of voluntary movement. Paralysis (-plegia) is a complete inability to perform any movement. […] Dysfunction may be of the upper motor neurons (cerebral motor cortex, subcortical structures, brainstem, and corticospinal tracts) or lower motor neurons (motor nuclei of the cranial nerves or motor neurons of the ventral horn of the spinal cord; or peripheral nerve, muscle, or neuromuscular junction). […] Spastic weakness: Upper motor neuron dysfunction. Commonly caused by stroke (ischemic or hemorrhagic), mass lesions (tumor, abscess), demyelination, or trauma. […] Flaccid weakness: Lower motor neuron dysfunction. Caused by neuropathy (Guillain-Barr syndrome, heavy metal poisoning, adverse effects of drugs [vincristine, isoniazid], neuropathy in patients with autoimmune diseases or diabetes, acute intermittent porphyria, nerve compression, critical illness myopathy, critical illness neuropathy), neuromuscular junction disorders (myasthenia gravis, botulism, effects of muscle relaxants, organophosphate poisoning), or muscle disorders (inflammatory myopathy: polymyositis, inclusion body myositis, dermatomyositis), muscular dystrophy, electrolyte abnormalities (among others, periodic paralysis in patients with hypokalemia or hyperkalemia, hypomagnesemia, hypercalcemia).

• #5 Paralysis | Causes, Symptoms & Treatment | Britannica

  https://www.britannica.com/science/paralysis

  The spinal cord is rarely the site of vascular obstruction or hemorrhage. Common causes of damage to the corticospinal tracts in the cord include deformities of the spinal column from bone and joint disease and from fracture or dislocation of the spine, spinal cord tumours, multiple sclerosis, strokes, and a number of inflammatory and degenerative diseases associated with pernicious anemia. […] Of the diseases that attack lower motor neurons and result in paralysis with muscular wasting, the most common are poliomyelitis and polyneuritis, the former affecting the cell bodies or the bulbar and spinal motor neurons and the latter affecting their peripheral processes. […] Diseases that result in paralysis through primary changes in muscle tissue are fewer than the above. […] Muscular weakness without structural alteration in nerve or muscle tissue may be a symptom of disturbances in metabolism arising from a wide variety of causes. Among such conditions are diseases of the endocrine glands, certain intoxications, and several metabolic defects.

• #6 Flaccid vs Spastic Paralysis: Causes, Differences, and Treatment Options

  https://www.flintrehab.com/spastic-vs-flaccid-paralysis/?srsltid=AfmBOop1ybk8JyE9ZW5CwcKjqhtJ-0C2DZ0eY0VJ0fgHnGkBi7_vISl6

  Paralysis refers to the complete or partial loss of muscle function. A neurological injury such as stroke or spinal cord injury can cause different types of paralysis, including spastic paralysis (caused by increased muscle tone) and flaccid paralysis (caused by reduced muscle tone). […] When certain parts of this neural pathway become damaged, spastic or flaccid paralysis may occur. […] For example, when upper motor neurons sustain damage, spasticity (muscle stiffness) or spastic paralysis may occur. On the other hand, damage to lower motor neurons may result in weakness, loss of muscle, twitching, or flaccid paralysis. […] Paralysis after a spinal cord injury occurs when the spinal cord is damaged, and nerves can no longer send signals from the brain to your muscles. This can cause paraplegia (paralysis in the lower limbs) or quadriplegia (paralysis in all four limbs).

• #7 Flaccid vs Spastic Paralysis: Causes, Differences, and Treatment Options

  https://www.flintrehab.com/spastic-vs-flaccid-paralysis/?srsltid=AfmBOop1ybk8JyE9ZW5CwcKjqhtJ-0C2DZ0eY0VJ0fgHnGkBi7_vISl6

  One key difference is that in spastic paralysis, the muscles remain in constant contraction and become rigid and immobile. On the other hand, in flaccid paralysis, the muscles cannot contract and, as a result, become floppy and immobile. […] Spastic paralysis can occur when the upper motor neurons become damaged, resulting in a loss of voluntary control over the affected muscles. […] Flaccid paralysis can occur when motor neurons become damaged, not allowing nerve impulses to reach the intended muscles. […] If flaccid paralysis is left untreated, the muscles can begin to atrophy (reduce in size and waste away). […] If spastic paralysis is left untreated, it can lead to frozen joints, shortened tendons and stiff muscles that can no longer be stretched. […] More serious complications, such as contractures or pressure sores on the skin, can also develop if paralysis is neglected. […] To reduce the chances of spastic or flaccid paralysis worsening or developing serious complications, its crucial to have a suitable rehabilitation exercise plan. […] Orthotic devices, electrical stimulation and electroacupuncture are most effective when combined with therapy exercises.

• #8 Paralysis | Causes, Symptoms & Treatment | Britannica

  https://www.britannica.com/science/paralysis

  paralysis, loss or impairment of voluntary muscular movement caused by structural abnormalities of nervous or muscular tissue or by metabolic disturbances in neuromuscular function. […] Most diseases that cause paralysis can be divided into two main groups depending on whether they entail structural alterations in nervous or muscular tissue, or lead to metabolic disturbances in neuromuscular function. […] The most common cause of hemiplegia is damage to the corticospinal tracts and associated motor tracts in one hemisphere of the brain from obstruction (blood clot or thrombosis) or rupture (cerebral hemorrhage) of a major cerebral artery. […] Bilateral hemiplegia with pseudobulbar palsy results from diffuse, bilateral brain diseases such as occurs in severe cerebral arteriosclerosis or cerebral vascular syphilis.

• #9 Paralysis: Symptoms, Causes, and Treatment

  https://www.verywellhealth.com/paralysis-5224673

  Paralysis describes complete or partial weakness of the body or part of the body. It can occur suddenly or gradually as a result of conditions that affect the brain, spinal cord, or nerves. […] Many different conditions can cause paralysis, including: Stroke: An interruption of blood flow in an artery in the brain can affect areas of the brain that control motor movement. Heart disease, high blood pressure, high cholesterol, and uncontrolled diabetes are common risk factors. […] Generally, paralysis or paresis of the face or the whole arm or leg will only involve one side of the body, and this is usually caused by a health condition affecting the brain or spinal cord. […] These issues may cause permanent paralysis, but prompt treatment can lessen the long-term severity of the weakness.

• #10

  https://resou.osaka-u.ac.jp/en/research/2012/20120402_1

  Clarification of mechanism of spontaneous recovery from paralysis after brain damage […] The impairment of neural networks by brain damage such as cerebral vascular disease or brain injury causes severe neurological symptoms such as limb paralysis. […] Through the use of mice, this group demonstrated that even after brain damage in major areas, the formation of new neural networks brings about a degree of spontaneous recovery of neural function and clarified mechanisms for such. […] It was long believed that central nerves such as the brain and spinal cord could not be regenerated once they were damaged, therefore, spontaneous functional recovery after injuries to the central nervous system gained little publicity and not been clarified scientifically. […] Clarification of the voluntary recovery mechanism of the brain will greatly contribute to the development of treatment methods for aftereffects following brain damage.

• #11

  https://resou.osaka-u.ac.jp/en/research/2012/20120402_1

  These experiment results show that the cerebral cortex on the undamaged side compensate for the functions of the damaged side and the paralyzed forefoot became capable of movement. […] It demonstrated that the new neural circuits formed in the cervical cord contributed to spontaneous recovery of motor function. […] From this evidence, it was clarified that BDNF-TrkB signaling is needed for the formation of new circuits after brain injury. […] This discovery will lead to the clarification of a mechanism of recovery of neural symptoms caused by cerebral vascular disorder and brain injury in humans and monkeys possessing higher neural network. […] Progress in this research will clarify the mechanism of self-recovery of the brain.

• #12 Chapter 18: Poliomyelitis | Pink Book | CDC

  https://www.cdc.gov/pinkbook/hcp/table-of-contents/chapter-18-poliomyelitis.html

  The virus enters through the mouth and multiplies in the oropharynx and gastrointestinal tract. […] Poliovirus-induced destruction of motor neurons of the anterior horn of the spinal cord and brain stem cells results in distinctive paralysis.

• #13 Poliomyelitis – Infectious Diseases – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/infectious-diseases/enteroviruses/poliomyelitis

  Poliovirus is shed in feces and saliva, and is transmitted via the fecal-oral or respiratory route. It then replicates in oropharyngeal and lower gastrointestinal tract mucosa and enters the cervical and mesenteric lymph nodes. A primary (minor) viremia follows with spread of virus to the reticuloendothelial system. Infection may be contained at this point, or the virus may further multiply and cause several days of secondary viremia, culminating in the development of symptoms and antibodies. […] In paralytic infections, poliovirus enters the central nervous system either via secondary viremia or retrograde migration through peripheral nerves. Significant damage occurs in the spinal cord and brainstem, particularly in the areas controlling motor and autonomic function. Inflammation compounds the damage produced by primary viral invasion. Factors predisposing to serious neurologic damage include increasing age, recent tonsillectomy or intramuscular injection, pregnancy, humoral immunodeficiency, and physical exertion concurrent with onset of the central nervous system phase. […] In paralytic poliomyelitis, about two thirds of patients have residual permanent weakness.

• #14 Chapter 18: Poliomyelitis | Pink Book | CDC

  https://www.cdc.gov/pinkbook/hcp/table-of-contents/chapter-18-poliomyelitis.html

  The virus enters through the mouth and multiplies in the oropharynx and gastrointestinal tract. […] Poliovirus-induced destruction of motor neurons of the anterior horn of the spinal cord and brain stem cells results in distinctive paralysis.

• #15 Poliomyelitis – Infectious Diseases – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/infectious-diseases/enteroviruses/poliomyelitis

  Poliovirus is shed in feces and saliva, and is transmitted via the fecal-oral or respiratory route. It then replicates in oropharyngeal and lower gastrointestinal tract mucosa and enters the cervical and mesenteric lymph nodes. A primary (minor) viremia follows with spread of virus to the reticuloendothelial system. Infection may be contained at this point, or the virus may further multiply and cause several days of secondary viremia, culminating in the development of symptoms and antibodies. […] In paralytic infections, poliovirus enters the central nervous system either via secondary viremia or retrograde migration through peripheral nerves. Significant damage occurs in the spinal cord and brainstem, particularly in the areas controlling motor and autonomic function. Inflammation compounds the damage produced by primary viral invasion. Factors predisposing to serious neurologic damage include increasing age, recent tonsillectomy or intramuscular injection, pregnancy, humoral immunodeficiency, and physical exertion concurrent with onset of the central nervous system phase. […] In paralytic poliomyelitis, about two thirds of patients have residual permanent weakness.

• #16 Paralysis | Causes, Symptoms & Treatment | Britannica

  https://www.britannica.com/science/paralysis

  The spinal cord is rarely the site of vascular obstruction or hemorrhage. Common causes of damage to the corticospinal tracts in the cord include deformities of the spinal column from bone and joint disease and from fracture or dislocation of the spine, spinal cord tumours, multiple sclerosis, strokes, and a number of inflammatory and degenerative diseases associated with pernicious anemia. […] Of the diseases that attack lower motor neurons and result in paralysis with muscular wasting, the most common are poliomyelitis and polyneuritis, the former affecting the cell bodies or the bulbar and spinal motor neurons and the latter affecting their peripheral processes. […] Diseases that result in paralysis through primary changes in muscle tissue are fewer than the above. […] Muscular weakness without structural alteration in nerve or muscle tissue may be a symptom of disturbances in metabolism arising from a wide variety of causes. Among such conditions are diseases of the endocrine glands, certain intoxications, and several metabolic defects.

• #17 Bell’s palsy – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/bells-palsy/symptoms-causes/syc-20370028

  Bell’s palsy also is known as acute peripheral facial palsy of unknown cause. […] Experts think it’s caused by swelling and irritation of the nerve that controls the muscles on one side of the face. Bell’s palsy could be caused by a reaction that occurs after a viral infection. […] In Bell’s palsy, that nerve becomes inflamed and swollen usually related to a viral infection. Besides affecting facial muscles, the nerve affects tears, saliva, taste and a small bone in the middle of the ear.

• #18 Vocal Cord Paralysis: Pathophysiology, Etiologies, and Evaluation

  https://www.ijhns.com/abstractArticleContentBrowse/IJHNS/27529/JPJ/fullText

  Vocal fold paralysis often leads to significant morbidity including dysphonia, dysphagia and aspiration. […] An appropriate understanding of the pathophysiology, etiologies, and a systematic method of evaluation are essential for discussing prognosis and offering patients appropriate treatments. […] Damage or injury to these nerves may result in vocal fold paresis or paralysis. […] Vocal fold paralysis implies complete vocal fold immobility due to neurological injury. […] It is important to differentiate between nerve conduction block and presence of axonal injury for prognostication purposes when possible. […] Most surgically induced nerve injuries are the result of pressure, crushing or heating intraoperatively, leaving the nerve macroscopically intact. […] Neuropraxia is the mildest form of injury, in which the Schwann cells are injured but the axon integrity is maintained, often resulting in a conduction block lasting for 6-8 weeks whilst the Schwann cells repair.

• #19 Vocal Cord Paralysis: Pathophysiology, Etiologies, and Evaluation

  https://www.ijhns.com/abstractArticleContentBrowse/IJHNS/27529/JPJ/fullText

  Axonotmesis is when axonal injury is present, leading to possible neuron death or reinnervation with variable functional outcomes. […] Acute unilateral paralysis of one RLN will cause denervation and loss of function to the TA, LCA, PCA, and IA muscles, with the IA being less affected due to additional nervous supply. […] The summation of these effects, seen in acute complete paralysis of one RLN, is the loss of vocal fold mass, abduction, and adduction resulting in glottic incompetence. […] The motor axons of the RLN contain four times as many adductor axons as there are abductor axons, and when nerve injury is followed by regeneration, these axons maintain their adductor and abductor affinity, however may regenerate inappropriately with distal axons of the opposite type. […] Laryngeal synkinesis is a form of defective healing where severed nerve sheaths do not accurately regenerate to their preinjury counterpart, causing uncoordinated muscle contraction.

• #20 Vocal Cord Paralysis: Pathophysiology, Etiologies, and Evaluation

  https://www.ijhns.com/abstractArticleContentBrowse/IJHNS/27529/JPJ/fullText

  Vocal fold paralysis often leads to significant morbidity including dysphonia, dysphagia and aspiration. […] An appropriate understanding of the pathophysiology, etiologies, and a systematic method of evaluation are essential for discussing prognosis and offering patients appropriate treatments. […] Damage or injury to these nerves may result in vocal fold paresis or paralysis. […] Vocal fold paralysis implies complete vocal fold immobility due to neurological injury. […] It is important to differentiate between nerve conduction block and presence of axonal injury for prognostication purposes when possible. […] Most surgically induced nerve injuries are the result of pressure, crushing or heating intraoperatively, leaving the nerve macroscopically intact. […] Neuropraxia is the mildest form of injury, in which the Schwann cells are injured but the axon integrity is maintained, often resulting in a conduction block lasting for 6-8 weeks whilst the Schwann cells repair.

• #21 Vocal Cord Paralysis: Pathophysiology, Etiologies, and Evaluation

  https://www.ijhns.com/abstractArticleContentBrowse/IJHNS/27529/JPJ/fullText

  Axonotmesis is when axonal injury is present, leading to possible neuron death or reinnervation with variable functional outcomes. […] Acute unilateral paralysis of one RLN will cause denervation and loss of function to the TA, LCA, PCA, and IA muscles, with the IA being less affected due to additional nervous supply. […] The summation of these effects, seen in acute complete paralysis of one RLN, is the loss of vocal fold mass, abduction, and adduction resulting in glottic incompetence. […] The motor axons of the RLN contain four times as many adductor axons as there are abductor axons, and when nerve injury is followed by regeneration, these axons maintain their adductor and abductor affinity, however may regenerate inappropriately with distal axons of the opposite type. […] Laryngeal synkinesis is a form of defective healing where severed nerve sheaths do not accurately regenerate to their preinjury counterpart, causing uncoordinated muscle contraction.

• #22 Diaphragmatic Paralysis: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/298200-overview

  The diaphragm, the most important muscle of ventilation, develops negative intrathoracic pressure to initiate ventilation. Innervated by cervical motor neurons C3-C5 via the phrenic nerves, these two nerves provide both sensory and motor function to the diaphragm. […] Diaphragmatic paralysis is an uncommon, yet underdiagnosed cause of dyspnea. […] Diaphragmatic paralyses encompass a spectrum of diseases involving a single leaflet, known as unilateral diaphragmatic paralysis (UDP), and that involving both leaflets, known as bilateral diaphragmatic paralysis (BDP). […] In bilateral diaphragmatic paralysis, accessory muscles assume some or all of the work of breathing by contracting more intensely. An increased effort in the struggle to breathe may fatigue the accessory muscles and lead to ventilatory failure.

• #23 Diaphragmatic paralysis pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Diaphragmatic_paralysis_pathophysiology

  It is thought that diaphragmatic paralysis is the result of paralysis of cervical nerve roots( C3-C5 ). […] Diaphragmatic paralysis can be unilateral or bilateral according to involvemnet of one or two leaflets of diaphragm. […] Diaphragmatic paralysis is an uncommon cause of dyspnea. […] It is understood that diaphragmatic paralysis is the result of paralysis of cervical nerve roots (C3-C5 ). […] In bilateral diaphragmatic paralysis, accessory muscles do all of the work of breathing and finally it may lead to ventilatory failure. […] Bilateral diaphragmatic paralysis is usually seen with generalized muscle weakness. In some cases, the diaphragm is the only muscle involved.

• #24 Diaphragmatic Paralysis: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/298200-overview

  The diaphragm, the most important muscle of ventilation, develops negative intrathoracic pressure to initiate ventilation. Innervated by cervical motor neurons C3-C5 via the phrenic nerves, these two nerves provide both sensory and motor function to the diaphragm. […] Diaphragmatic paralysis is an uncommon, yet underdiagnosed cause of dyspnea. […] Diaphragmatic paralyses encompass a spectrum of diseases involving a single leaflet, known as unilateral diaphragmatic paralysis (UDP), and that involving both leaflets, known as bilateral diaphragmatic paralysis (BDP). […] In bilateral diaphragmatic paralysis, accessory muscles assume some or all of the work of breathing by contracting more intensely. An increased effort in the struggle to breathe may fatigue the accessory muscles and lead to ventilatory failure.

• #25 Diaphragmatic Paralysis: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/298200-overview

  The most common causes are secondary to motor neuron disease, including amyotrophic lateral sclerosis and postpolio syndrome. […] The prognosis depends on the nature of the underlying disease. Patients with bilateral diaphragmatic paralysis are usually symptomatic and, when symptoms are severe or in the presence of underlying lung pathology, may develop ventilatory failure without medical intervention.

• #26 Hyperkalemic periodic paralysis – Wikipedia

  https://en.wikipedia.org/wiki/Hyperkalemic_periodic_paralysis

  Hyperkalemic periodic paralysis (HYPP, HyperKPP) is an inherited autosomal dominant disorder that affects sodium channels in muscle cells and the ability to regulate potassium levels in the blood. It is characterized by muscle hyperexcitability or weakness which, exacerbated by potassium, heat or cold, can lead to uncontrolled shaking followed by paralysis. […] The mutation causing this disorder is autosomal dominant on the SCN4A gene with linkage to the sodium channel expressed in muscle. The mutation causes single amino acid changes in parts of the channel which are important for inactivation. These mutations impair „ball and chain” fast inactivation of SCN4A following an action potential. […] Mutations altering the usual structure and function of this sodium channel therefore disrupt regulation of muscle contraction, leading to episodes of severe muscle weakness or paralysis. Mutations have been identified in residues between transmembrane domains III and IV which make up the fast inactivation gate of Nav1.4.

• #27 Hyperkalemic periodic paralysis – Wikipedia

  https://en.wikipedia.org/wiki/Hyperkalemic_periodic_paralysis

  Hyperkalemic periodic paralysis (HYPP, HyperKPP) is an inherited autosomal dominant disorder that affects sodium channels in muscle cells and the ability to regulate potassium levels in the blood. It is characterized by muscle hyperexcitability or weakness which, exacerbated by potassium, heat or cold, can lead to uncontrolled shaking followed by paralysis. […] The mutation causing this disorder is autosomal dominant on the SCN4A gene with linkage to the sodium channel expressed in muscle. The mutation causes single amino acid changes in parts of the channel which are important for inactivation. These mutations impair „ball and chain” fast inactivation of SCN4A following an action potential. […] Mutations altering the usual structure and function of this sodium channel therefore disrupt regulation of muscle contraction, leading to episodes of severe muscle weakness or paralysis. Mutations have been identified in residues between transmembrane domains III and IV which make up the fast inactivation gate of Nav1.4.

• #28 Hyperkalemic periodic paralysis – UpToDate

  https://www.uptodate.com/contents/hyperkalemic-periodic-paralysis

  Hyperkalemic PP is an autosomal dominant condition with nearly complete penetrance. The cause of hyperkalemic PP is a change in a gene that regulates the production of a protein (SCN4A) in the sodium channel of skeletal muscle. The gene is located in chromosome 17q23, and is known as SCN4A. […] At least nine different mutations in this gene have been identified that can cause hyperkalemic PP.

• #29 Hyperkalemic periodic paralysis – Wikipedia

  https://en.wikipedia.org/wiki/Hyperkalemic_periodic_paralysis

  The pathological mechanism of SCN4A mutations in hyperkalemic periodic paralysis is complex, but explains the autosomal dominant and hyperkalemia-related aspects of the disease. In patients with mutations in SCN4A, not all copies of the channel inactivate following the action potential. This results in a sodium leak and failure to return to the original resting membrane potential. In the presence of hyperkalemia, which causes an additional chronic depolarization of the membrane potential, this sodium leak raises the membrane potential to the point that all sodium channels, including channels produced from the wild-type allele and mutant channels that did inactivate, fail to be release from inactivation (enter depolarization block). Since the motor end plate is depolarised, further signals to contract have no effect (paralysis).

• #30 Mechanism of Thyrotoxic Periodic Paralysis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3358768/

  The pathogenesis of thyrotoxic periodic paralysis has long been thought related to increased Na+K+ ATPase activity stimulated by thyroid hormone and/or hyperadrenergic activity and hyperinsulinemia. […] Recent findings that loss of function mutations of the skeletal muscle-specific inward rectifying K+ (Kir) channel, Kir2.6, associate with thyrotoxic periodic paralysis provide new insights into how reduced outward K+ efflux in skeletal muscle, from either channel mutations or inhibition by hormones (adrenalin or insulin), can lead to a vicious cycle of hypokalemia and paradoxical depolarization, which in turn, inactivates Na+ channels and causes muscle unexcitability and paralysis. […] The important role of Na+K+ ATPase pumps in the pathogenesis of TPP is supported by the finding that their activity in the skeletal muscle is significantly increased.

• #31

  https://journals.lww.com/jasn/fulltext/2012/06000/mechanism_of_thyrotoxic_periodic_paralysis.8.aspx

  The pathogenesis of thyrotoxic periodic paralysis has long been thought related to increased Na+K+ ATPase activity stimulated by thyroid hormone and/or hyperadrenergic activity and hyperinsulinemia. […] This mechanism alone, however, cannot adequately explain how hypokalemia occurs during acute attacks or the associated paradoxical depolarization of the resting membrane potential. […] Recent findings that loss of function mutations of the skeletal muscle-specific inward rectifying K+ (Kir) channel, Kir2.6, associate with thyrotoxic periodic paralysis provide new insights into how reduced outward K+ efflux in skeletal muscle, from either channel mutations or inhibition by hormones (adrenalin or insulin), can lead to a vicious cycle of hypokalemia and paradoxical depolarization, which in turn, inactivates Na+ channels and causes muscle unexcitability and paralysis.

• #32 Mechanism of Thyrotoxic Periodic Paralysis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3358768/

  The pathogenesis of thyrotoxic periodic paralysis has long been thought related to increased Na+K+ ATPase activity stimulated by thyroid hormone and/or hyperadrenergic activity and hyperinsulinemia. […] Recent findings that loss of function mutations of the skeletal muscle-specific inward rectifying K+ (Kir) channel, Kir2.6, associate with thyrotoxic periodic paralysis provide new insights into how reduced outward K+ efflux in skeletal muscle, from either channel mutations or inhibition by hormones (adrenalin or insulin), can lead to a vicious cycle of hypokalemia and paradoxical depolarization, which in turn, inactivates Na+ channels and causes muscle unexcitability and paralysis. […] The important role of Na+K+ ATPase pumps in the pathogenesis of TPP is supported by the finding that their activity in the skeletal muscle is significantly increased.

• #33

  https://journals.lww.com/jasn/fulltext/2012/06000/mechanism_of_thyrotoxic_periodic_paralysis.8.aspx

  The pathogenesis of thyrotoxic periodic paralysis has long been thought related to increased Na+K+ ATPase activity stimulated by thyroid hormone and/or hyperadrenergic activity and hyperinsulinemia. […] This mechanism alone, however, cannot adequately explain how hypokalemia occurs during acute attacks or the associated paradoxical depolarization of the resting membrane potential. […] Recent findings that loss of function mutations of the skeletal muscle-specific inward rectifying K+ (Kir) channel, Kir2.6, associate with thyrotoxic periodic paralysis provide new insights into how reduced outward K+ efflux in skeletal muscle, from either channel mutations or inhibition by hormones (adrenalin or insulin), can lead to a vicious cycle of hypokalemia and paradoxical depolarization, which in turn, inactivates Na+ channels and causes muscle unexcitability and paralysis.

• #34 Mechanism of Thyrotoxic Periodic Paralysis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3358768/

  Thyroid hormone can stimulate Na+K+ ATPase in skeletal muscle by genomic mechanism, acting on the thyroid hormone responsive elements to upregulate the transcription of the gene encoding Na+K+ ATPase, and through nongenomic mechanisms by enhancing the intrinsic activity or promoting membrane insertion of the pump. […] Hyperinsulinemia is also observed in acute attack of TPP, and the release of insulin in response to oral glucose challenge is exaggerated in TPP patients, supporting the idea that insulin participates in the pathogenesis of hypokalemia in TPP. […] Two recent studies report that mutations in the gene encoding Kir2.6, a skeletal muscle-specific Kir channel, are associated with TPP and predispose these patients to acute paralytic attacks. […] Overall, these two recent papers provide compelling support for the role of genetic mutations in Kir2.6 channel in the pathogenesis of TPP.

• #35 Mechanism of Thyrotoxic Periodic Paralysis

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3358768/

  Thyroid hormone can stimulate Na+K+ ATPase in skeletal muscle by genomic mechanism, acting on the thyroid hormone responsive elements to upregulate the transcription of the gene encoding Na+K+ ATPase, and through nongenomic mechanisms by enhancing the intrinsic activity or promoting membrane insertion of the pump. […] Hyperinsulinemia is also observed in acute attack of TPP, and the release of insulin in response to oral glucose challenge is exaggerated in TPP patients, supporting the idea that insulin participates in the pathogenesis of hypokalemia in TPP. […] Two recent studies report that mutations in the gene encoding Kir2.6, a skeletal muscle-specific Kir channel, are associated with TPP and predispose these patients to acute paralytic attacks. […] Overall, these two recent papers provide compelling support for the role of genetic mutations in Kir2.6 channel in the pathogenesis of TPP.

• #36 Thyrotoxic Periodic Paralysis: An Update | Chakraborty | Journal of Endocrinology and Metabolism

  https://jofem.org/index.php/jofem/article/view/662/284284456

  According to evidences available at present that the combined defect of both inward K+ channel (Na+-K+ ATPase) and inward rectifier K+ channel (Kir2.6) present in some patients of thyrotoxicosis gives rise to episodes of TPP. The combined gain and loss function mutations in these two channels may be the cause. Gain of function mutation causes hyper-polarization and impaired action potential discharge in Kir2.6 channel (KCNJ18). […] The ethnic variation of TPP has been well recognized but underlying cause is yet to be unveiled. Ethnic variation of Na+-K+ ATPase activity or Kir2.6 inward rectifier channel may be the underlying cause. Though there are chances of other ion channels underlying the disorder. As only up to 33% of TPP cases have shown Kir2.6 mutations in United States, France and Brazil genetic study. Ethnic variation of red cell Na+-K+ ATPase activity has been seen, but no similar study on muscle Na+-K+ ATPase on TTP patients undertaken. So there is scope for future research in this field. […] We are sure that further genetic study would tell us the cause of higher susceptibility of Asians for TPP. Moreover male preponderance could be due to any role of androgen receptor or its downstream interactions with muscle ion channels.

• #37 Thyrotoxic Periodic Paralysis: An Update | Chakraborty | Journal of Endocrinology and Metabolism

  https://jofem.org/index.php/jofem/article/view/662/284284456

  According to evidences available at present that the combined defect of both inward K+ channel (Na+-K+ ATPase) and inward rectifier K+ channel (Kir2.6) present in some patients of thyrotoxicosis gives rise to episodes of TPP. The combined gain and loss function mutations in these two channels may be the cause. Gain of function mutation causes hyper-polarization and impaired action potential discharge in Kir2.6 channel (KCNJ18). […] The ethnic variation of TPP has been well recognized but underlying cause is yet to be unveiled. Ethnic variation of Na+-K+ ATPase activity or Kir2.6 inward rectifier channel may be the underlying cause. Though there are chances of other ion channels underlying the disorder. As only up to 33% of TPP cases have shown Kir2.6 mutations in United States, France and Brazil genetic study. Ethnic variation of red cell Na+-K+ ATPase activity has been seen, but no similar study on muscle Na+-K+ ATPase on TTP patients undertaken. So there is scope for future research in this field. […] We are sure that further genetic study would tell us the cause of higher susceptibility of Asians for TPP. Moreover male preponderance could be due to any role of androgen receptor or its downstream interactions with muscle ion channels.

• #38 Tick Paralysis in Animals – Nervous System – Merck Veterinary Manual

  https://www.merckvetmanual.com/nervous-system/tick-paralysis/tick-paralysis-in-animals

  Tick paralysis is unique among toxicoses because it is due to pulsed toxin flow associated with repeated tick feeding over a set period of time. […] The potential to induce tick paralysis has been demonstrated, described, or suspected in 64 species of ticks belonging to 7 ixodid and 8 argasid genera. […] The severity of this neurotoxicosis does not necessarily relate directly to tick size, number, or duration of attachment. […] The toxin is presumed to travel from the attachment site via the lymph to the systemic circulation and then to all areas of the body, where it has a direct effect on cellular potassium channels and thus on intracellular calcium levels. […] Systemic toxicosis follows injection of toxin into the host, especially during periods of rapid engorgement, although large numbers of larval or nymphal ticks may also cause paralysis.

• #39 Tick Paralysis in Animals – Nervous System – Merck Veterinary Manual

  https://www.merckvetmanual.com/nervous-system/tick-paralysis/tick-paralysis-in-animals

  Tick paralysis is unique among toxicoses because it is due to pulsed toxin flow associated with repeated tick feeding over a set period of time. […] The potential to induce tick paralysis has been demonstrated, described, or suspected in 64 species of ticks belonging to 7 ixodid and 8 argasid genera. […] The severity of this neurotoxicosis does not necessarily relate directly to tick size, number, or duration of attachment. […] The toxin is presumed to travel from the attachment site via the lymph to the systemic circulation and then to all areas of the body, where it has a direct effect on cellular potassium channels and thus on intracellular calcium levels. […] Systemic toxicosis follows injection of toxin into the host, especially during periods of rapid engorgement, although large numbers of larval or nymphal ticks may also cause paralysis.

• #40 Tick paralysis – Wikipedia

  https://en.wikipedia.org/wiki/Tick_paralysis

  Tick paralysis is believed to be due to toxins found in the engorged female tick’s saliva that enter the bloodstream while the tick is feeding. […] Tick paralysis occurs when an engorged and gravid (egg-laden) female tick produces a neurotoxin in its salivary glands and transmits it to its host during feeding. […] Experiments have indicated that the greatest amount of toxin is produced between the fifth and seventh day of attachment (often initiating or increasing the severity of symptoms), although the timing may vary depending on the species of tick. […] Unlike Lyme disease, ehrlichiosis, and babesiosis, which are caused by the systemic proliferation and expansion of microbes after the offending tick is gone, tick paralysis is chemically induced by the tick and therefore usually only continues in its presence. Once the tick is removed, symptoms usually diminish rapidly. However, in some cases, profound paralysis can develop and even become fatal before anyone becomes aware of a tick’s presence.

• #41 Tick paralysis – Wikipedia

  https://en.wikipedia.org/wiki/Tick_paralysis

  Tick paralysis is believed to be due to toxins found in the engorged female tick’s saliva that enter the bloodstream while the tick is feeding. […] Tick paralysis occurs when an engorged and gravid (egg-laden) female tick produces a neurotoxin in its salivary glands and transmits it to its host during feeding. […] Experiments have indicated that the greatest amount of toxin is produced between the fifth and seventh day of attachment (often initiating or increasing the severity of symptoms), although the timing may vary depending on the species of tick. […] Unlike Lyme disease, ehrlichiosis, and babesiosis, which are caused by the systemic proliferation and expansion of microbes after the offending tick is gone, tick paralysis is chemically induced by the tick and therefore usually only continues in its presence. Once the tick is removed, symptoms usually diminish rapidly. However, in some cases, profound paralysis can develop and even become fatal before anyone becomes aware of a tick’s presence.

• #42 Tick paralysis – Wikipedia

  https://en.wikipedia.org/wiki/Tick_paralysis

  The neurotoxin structure and gene, at least for the tick species Ixodes holocyclus have since been identified and are called holocyclotoxins after the species. At least three members (HT-1, HT-3, and HT-12) trigger paralysis by presynaptic inhibition of neurotransmitter release via a calcium dependent mechanism resulting in a reduction of quantal content, and loss of effective neuromuscular synaptic transmission.

• #43 Tick holocyclotoxins trigger host paralysis by presynaptic inhibition | Scientific Reports

  https://www.nature.com/articles/srep29446

  The decrease in EPP amplitudes with maintained amplitude of MEPPs indicates the HTs act via a presynaptic mechanism. The holocyclotoxins likely change a stage between depolarisation and the calcium dependent release of vesicles, without affecting the release mechanism since MEPP frequency was unaffected. […] The findings of the present study further this observation and strongly support those of Cooper and co-worker, which proposed the inhibition of transmitter release due to a reduction in quantal content, but not quantal size. Our findings suggest that HTs reduction of quantal transmitter release is mediated via a reduction in calcium entry into the nerve terminal, likely achieved by an inhibitory effect on VGCCs. […] In this study, we have presented functional evidence indicating that members of the holocyclotoxin family inhibit neurotransmitter release via a calcium dependent mechanism resulting in a reduction of quantal content, and loss of effective neuromuscular synaptic transmission.

• #44 Tick holocyclotoxins trigger host paralysis by presynaptic inhibition | Scientific Reports

  https://www.nature.com/articles/srep29446

  Ticks are important vectors of pathogens and secreted neurotoxins with approximately 69 out of 692 tick species having the ability to induce severe toxicoses in their hosts. The Australian paralysis tick (Ixodes holocyclus) is known to be one of the most virulent tick species producing a flaccid paralysis and fatalities caused by a family of neurotoxins known as holocyclotoxins (HTs). The paralysis mechanism of these toxins is temperature dependent and is thought to involve inhibition of acetylcholine levels at the neuromuscular junction. However, the target and mechanism of this inhibition remain uncharacterised. […] Here, we report that three members of the holocyclotoxin family; HT-1 (GenBank AY766147), HT-3 (GenBank KP096303) and HT-12 (GenBank KP963967) induce muscle paralysis by inhibiting the dependence of transmitter release on extracellular calcium.

• #45 Tick holocyclotoxins trigger host paralysis by presynaptic inhibition | Scientific Reports

  https://www.nature.com/articles/srep29446

  The decrease in EPP amplitudes with maintained amplitude of MEPPs indicates the HTs act via a presynaptic mechanism. The holocyclotoxins likely change a stage between depolarisation and the calcium dependent release of vesicles, without affecting the release mechanism since MEPP frequency was unaffected. […] The findings of the present study further this observation and strongly support those of Cooper and co-worker, which proposed the inhibition of transmitter release due to a reduction in quantal content, but not quantal size. Our findings suggest that HTs reduction of quantal transmitter release is mediated via a reduction in calcium entry into the nerve terminal, likely achieved by an inhibitory effect on VGCCs. […] In this study, we have presented functional evidence indicating that members of the holocyclotoxin family inhibit neurotransmitter release via a calcium dependent mechanism resulting in a reduction of quantal content, and loss of effective neuromuscular synaptic transmission.

• #46 Tick Paralysis in Animals – Nervous System – Merck Veterinary Manual

  https://www.merckvetmanual.com/nervous-system/tick-paralysis/tick-paralysis-in-animals

  Tick paralysis is unique among toxicoses because it is due to pulsed toxin flow associated with repeated tick feeding over a set period of time. […] The potential to induce tick paralysis has been demonstrated, described, or suspected in 64 species of ticks belonging to 7 ixodid and 8 argasid genera. […] The severity of this neurotoxicosis does not necessarily relate directly to tick size, number, or duration of attachment. […] The toxin is presumed to travel from the attachment site via the lymph to the systemic circulation and then to all areas of the body, where it has a direct effect on cellular potassium channels and thus on intracellular calcium levels. […] Systemic toxicosis follows injection of toxin into the host, especially during periods of rapid engorgement, although large numbers of larval or nymphal ticks may also cause paralysis.

• #47

  https://link.springer.com/article/10.1007/BF00783470

  Using the crossed phrenic phenomenon as a test, the authors demonstrated that respiratory paralysis in botulism was caused by depression of motor innervation function of respiratory muscles and not by the exclusion activity of the respiratory center. […] Disturbances of respiration in tetanus and diphtheria are due to another, more complicated mechanism.

• #48 Pathophysiology and Treatment of Functional Paralysis: Insight from Transcranial Magnetic Stimulation

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9954472/

  Functional paralysis (FP) or limb weakness is a common presentation of functional movement disorders (FMD), accounting for 18.1% of the clinical manifestations of FMD. The pathophysiology of FP is not known, but imaging studies have identified changes in structural and functional connectivity in multiple brain networks. […] To date, the pathophysiology of FP is not known, and laboratory tests to adequately support clinical diagnosis are lacking. Imaging studies have identified changes in structural and functional connectivity in multiple brain areas, including the supplementary motor area and the temporoparietal junction. […] Evidence from neuroimaging studies suggests that noninvasive brain stimulation techniques may play a key role in the understanding of the pathophysiology of FMD and may represent a possible therapeutic option.

• #49 Pathophysiology and Treatment of Functional Paralysis: Insight from Transcranial Magnetic Stimulation

  https://www.mdpi.com/2076-3425/13/2/352

  Functional paralysis (FP) or limb weakness is a common presentation of functional movement disorders (FMD), accounting for 18.1% of the clinical manifestations of FMD. […] To date, the pathophysiology of FP is not known, and laboratory tests to adequately support clinical diagnosis are lacking. […] Imaging studies have identified changes in structural and functional connectivity in multiple brain areas, including the supplementary motor area and the temporoparietal junction. […] Evidence from neuroimaging studies suggests that noninvasive brain stimulation techniques may play a key role in the understanding of the pathophysiology of FMD and may represent a possible therapeutic option. […] Previous explanations for FP have proposed that it may be caused by inhibitory influence over the primary motor area (M1) by the orbitofrontal and cingulate cortex, despite physiological activity in premotor areas.

• #50 Pathophysiology and Treatment of Functional Paralysis: Insight from Transcranial Magnetic Stimulation

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9954472/

  Functional paralysis (FP) or limb weakness is a common presentation of functional movement disorders (FMD), accounting for 18.1% of the clinical manifestations of FMD. The pathophysiology of FP is not known, but imaging studies have identified changes in structural and functional connectivity in multiple brain networks. […] To date, the pathophysiology of FP is not known, and laboratory tests to adequately support clinical diagnosis are lacking. Imaging studies have identified changes in structural and functional connectivity in multiple brain areas, including the supplementary motor area and the temporoparietal junction. […] Evidence from neuroimaging studies suggests that noninvasive brain stimulation techniques may play a key role in the understanding of the pathophysiology of FMD and may represent a possible therapeutic option.

• #51 Pathophysiology and Treatment of Functional Paralysis: Insight from Transcranial Magnetic Stimulation

  https://www.mdpi.com/2076-3425/13/2/352

  Functional paralysis (FP) or limb weakness is a common presentation of functional movement disorders (FMD), accounting for 18.1% of the clinical manifestations of FMD. […] To date, the pathophysiology of FP is not known, and laboratory tests to adequately support clinical diagnosis are lacking. […] Imaging studies have identified changes in structural and functional connectivity in multiple brain areas, including the supplementary motor area and the temporoparietal junction. […] Evidence from neuroimaging studies suggests that noninvasive brain stimulation techniques may play a key role in the understanding of the pathophysiology of FMD and may represent a possible therapeutic option. […] Previous explanations for FP have proposed that it may be caused by inhibitory influence over the primary motor area (M1) by the orbitofrontal and cingulate cortex, despite physiological activity in premotor areas.

• #52 Pathophysiology and Treatment of Functional Paralysis: Insight from Transcranial Magnetic Stimulation

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9954472/

  Functional paralysis (FP) or limb weakness is a common presentation of functional movement disorders (FMD), accounting for 18.1% of the clinical manifestations of FMD. The pathophysiology of FP is not known, but imaging studies have identified changes in structural and functional connectivity in multiple brain networks. […] To date, the pathophysiology of FP is not known, and laboratory tests to adequately support clinical diagnosis are lacking. Imaging studies have identified changes in structural and functional connectivity in multiple brain areas, including the supplementary motor area and the temporoparietal junction. […] Evidence from neuroimaging studies suggests that noninvasive brain stimulation techniques may play a key role in the understanding of the pathophysiology of FMD and may represent a possible therapeutic option.

• #53 Pathophysiology and Treatment of Functional Paralysis: Insight from Transcranial Magnetic Stimulation

  https://www.mdpi.com/2076-3425/13/2/352

  Functional paralysis (FP) or limb weakness is a common presentation of functional movement disorders (FMD), accounting for 18.1% of the clinical manifestations of FMD. […] To date, the pathophysiology of FP is not known, and laboratory tests to adequately support clinical diagnosis are lacking. […] Imaging studies have identified changes in structural and functional connectivity in multiple brain areas, including the supplementary motor area and the temporoparietal junction. […] Evidence from neuroimaging studies suggests that noninvasive brain stimulation techniques may play a key role in the understanding of the pathophysiology of FMD and may represent a possible therapeutic option. […] Previous explanations for FP have proposed that it may be caused by inhibitory influence over the primary motor area (M1) by the orbitofrontal and cingulate cortex, despite physiological activity in premotor areas.

• #53 Pathophysiology and Treatment of Functional Paralysis: Insight from Transcranial Magnetic Stimulation

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9954472/

  Functional paralysis (FP) or limb weakness is a common presentation of functional movement disorders (FMD), accounting for 18.1% of the clinical manifestations of FMD. The pathophysiology of FP is not known, but imaging studies have identified changes in structural and functional connectivity in multiple brain networks. […] To date, the pathophysiology of FP is not known, and laboratory tests to adequately support clinical diagnosis are lacking. Imaging studies have identified changes in structural and functional connectivity in multiple brain areas, including the supplementary motor area and the temporoparietal junction. […] Evidence from neuroimaging studies suggests that noninvasive brain stimulation techniques may play a key role in the understanding of the pathophysiology of FMD and may represent a possible therapeutic option.

• #54 Pathophysiology and Treatment of Functional Paralysis: Insight from Transcranial Magnetic Stimulation

  https://www.mdpi.com/2076-3425/13/2/352

  Functional paralysis (FP) or limb weakness is a common presentation of functional movement disorders (FMD), accounting for 18.1% of the clinical manifestations of FMD. […] To date, the pathophysiology of FP is not known, and laboratory tests to adequately support clinical diagnosis are lacking. […] Imaging studies have identified changes in structural and functional connectivity in multiple brain areas, including the supplementary motor area and the temporoparietal junction. […] Evidence from neuroimaging studies suggests that noninvasive brain stimulation techniques may play a key role in the understanding of the pathophysiology of FMD and may represent a possible therapeutic option. […] Previous explanations for FP have proposed that it may be caused by inhibitory influence over the primary motor area (M1) by the orbitofrontal and cingulate cortex, despite physiological activity in premotor areas.

• #55 Pathophysiology and Treatment of Functional Paralysis: Insight from Transcranial Magnetic Stimulation

  https://www.mdpi.com/2076-3425/13/2/352

  Functional paralysis (FP) or limb weakness is a common presentation of functional movement disorders (FMD), accounting for 18.1% of the clinical manifestations of FMD. […] To date, the pathophysiology of FP is not known, and laboratory tests to adequately support clinical diagnosis are lacking. […] Imaging studies have identified changes in structural and functional connectivity in multiple brain areas, including the supplementary motor area and the temporoparietal junction. […] Evidence from neuroimaging studies suggests that noninvasive brain stimulation techniques may play a key role in the understanding of the pathophysiology of FMD and may represent a possible therapeutic option. […] Previous explanations for FP have proposed that it may be caused by inhibitory influence over the primary motor area (M1) by the orbitofrontal and cingulate cortex, despite physiological activity in premotor areas.

• #56 Pathophysiology and Treatment of Functional Paralysis: Insight from Transcranial Magnetic Stimulation

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9954472/

  A relevant contribution to the understanding of the pathophysiology of FP has been made by TMS studies. […] The first paper investigating M1 excitability using TMS in a patient with functional hemiparesis was published in 2008 by Geraldes and colleagues, and it showed asymmetric resting motor threshold (RMT) with higher values in the affected hemisphere. […] Because of the normal F wave and abnormal M1 excitability on the affected side, the authors proposed that increased inhibitory activation of M1 could be the most likely cause of FP. […] The largest study on M1 excitability in FP has been performed recently by Benussi and colleagues, who measured RMT, SICI and ICF in 21 patients affected by acute onset flaccid FP in the affected and non-affected M1. Findings included increased RMT in the affected M1, compared both to the unaffected side and healthy controls.

• #57 Pathophysiology and Treatment of Functional Paralysis: Insight from Transcranial Magnetic Stimulation

  https://www.mdpi.com/2076-3425/13/2/352

  In the past two decades, significant advances have been made in understanding the pathophysiology of FP, showing evidence of several deranged neural mechanisms, including those implicated in motor control and preparation. […] A relevant contribution to the understanding of the pathophysiology of FP has been made by TMS studies. […] The largest study on M1 excitability in FP has been performed recently by Benussi and colleagues, who measured RMT, SICI and ICF in 21 patients affected by acute onset flaccid FP in the affected and non-affected M1. Findings included increased RMT in the affected M1, compared both to the unaffected side and healthy controls. […] The asymmetry/imbalance of SICI between the affected and unaffected motor cortex could represent a disease-specific electrophysiological finding. […] In conclusion, rTMS appears to have a potential role as a safe and viable option for the treatment of FP; however, more studies are needed to investigate optimal stimulation parameters and clarify its role in the context of other therapeutical options.

• #58 Pathophysiology and Treatment of Functional Paralysis: Insight from Transcranial Magnetic Stimulation

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9954472/

  A relevant contribution to the understanding of the pathophysiology of FP has been made by TMS studies. […] The first paper investigating M1 excitability using TMS in a patient with functional hemiparesis was published in 2008 by Geraldes and colleagues, and it showed asymmetric resting motor threshold (RMT) with higher values in the affected hemisphere. […] Because of the normal F wave and abnormal M1 excitability on the affected side, the authors proposed that increased inhibitory activation of M1 could be the most likely cause of FP. […] The largest study on M1 excitability in FP has been performed recently by Benussi and colleagues, who measured RMT, SICI and ICF in 21 patients affected by acute onset flaccid FP in the affected and non-affected M1. Findings included increased RMT in the affected M1, compared both to the unaffected side and healthy controls.

• #59 Pathophysiology and Treatment of Functional Paralysis: Insight from Transcranial Magnetic Stimulation

  https://www.mdpi.com/2076-3425/13/2/352

  In the past two decades, significant advances have been made in understanding the pathophysiology of FP, showing evidence of several deranged neural mechanisms, including those implicated in motor control and preparation. […] A relevant contribution to the understanding of the pathophysiology of FP has been made by TMS studies. […] The largest study on M1 excitability in FP has been performed recently by Benussi and colleagues, who measured RMT, SICI and ICF in 21 patients affected by acute onset flaccid FP in the affected and non-affected M1. Findings included increased RMT in the affected M1, compared both to the unaffected side and healthy controls. […] The asymmetry/imbalance of SICI between the affected and unaffected motor cortex could represent a disease-specific electrophysiological finding. […] In conclusion, rTMS appears to have a potential role as a safe and viable option for the treatment of FP; however, more studies are needed to investigate optimal stimulation parameters and clarify its role in the context of other therapeutical options.

• #60 Pathophysiology and Treatment of Functional Paralysis: Insight from Transcranial Magnetic Stimulation

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9954472/

  The asymmetry/imbalance of SICI between the affected and unaffected motor cortex could represent a disease-specific electrophysiological finding. […] In conclusion, rTMS appears to have a potential role as a safe and viable option for the treatment of FP; however, more studies are needed to investigate optimal stimulation parameters and clarify its role in the context of other therapeutical options.

• #61 Pathophysiology and Treatment of Functional Paralysis: Insight from Transcranial Magnetic Stimulation

  https://www.mdpi.com/2076-3425/13/2/352

  In the past two decades, significant advances have been made in understanding the pathophysiology of FP, showing evidence of several deranged neural mechanisms, including those implicated in motor control and preparation. […] A relevant contribution to the understanding of the pathophysiology of FP has been made by TMS studies. […] The largest study on M1 excitability in FP has been performed recently by Benussi and colleagues, who measured RMT, SICI and ICF in 21 patients affected by acute onset flaccid FP in the affected and non-affected M1. Findings included increased RMT in the affected M1, compared both to the unaffected side and healthy controls. […] The asymmetry/imbalance of SICI between the affected and unaffected motor cortex could represent a disease-specific electrophysiological finding. […] In conclusion, rTMS appears to have a potential role as a safe and viable option for the treatment of FP; however, more studies are needed to investigate optimal stimulation parameters and clarify its role in the context of other therapeutical options.

• #62 The Science Behind Sleep Paralysis – President’s Writing Awards

  https://www.boisestate.edu/presidents-writing-awards/the-science-behind-sleep-paralysis/

  Sleep paralysis (SP) is a feeling of being conscious but unable to move. It occurs when a person passes between stages of wakefulness and sleep. […] The pathophysiology, or the physiological processes associated with SP, has shown that sleep paralysis occurs at the sleep-onset REM (rapid eye movement) period of sleep. Evidence suggests that sleep paralysis is caused by an overlap of REM sleep and wakefulness. […] Sleep paralysis is a haunting sleep disorder that can affect many people, and is caused by a simple overlap of waking up and rapid eye movement.

• #63 The Science Behind Sleep Paralysis – President’s Writing Awards

  https://www.boisestate.edu/presidents-writing-awards/the-science-behind-sleep-paralysis/

  Sleep paralysis (SP) is a feeling of being conscious but unable to move. It occurs when a person passes between stages of wakefulness and sleep. […] The pathophysiology, or the physiological processes associated with SP, has shown that sleep paralysis occurs at the sleep-onset REM (rapid eye movement) period of sleep. Evidence suggests that sleep paralysis is caused by an overlap of REM sleep and wakefulness. […] Sleep paralysis is a haunting sleep disorder that can affect many people, and is caused by a simple overlap of waking up and rapid eye movement.

• #64 How sleep paralysis works | University of Toronto

  https://www.utoronto.ca/news/how-sleep-paralysis-works

  New University of Toronto research shows that two powerful brain chemical systems work together to paralyze skeletal muscles during rapid eye movement (REM) sleep. […] Understanding the precise mechanism behind these chemicals role in REM sleep disorder is particularly important because about 80 percent of people who have it eventually develop a neurodegenerative disease, such as Parkinsons disease, said study author John Peever, PhD, a U of T neuroscientist. […] „We showed that GABA and glycine shut off motor neurons during REM sleep and that’s what triggers REM paralysis,” said Peever. […] The data suggest the two neurotransmitters must both be present together to maintain motor control during sleep, rather than working separately. […] By identifying the neurotransmitters and receptors involved in sleep-related paralysis, this study points us to possible molecular targets for developing treatments for sleep-related motor disorders, which can often be debilitating, McGinty said.

• #65 How sleep paralysis works | University of Toronto

  https://www.utoronto.ca/news/how-sleep-paralysis-works

  New University of Toronto research shows that two powerful brain chemical systems work together to paralyze skeletal muscles during rapid eye movement (REM) sleep. […] Understanding the precise mechanism behind these chemicals role in REM sleep disorder is particularly important because about 80 percent of people who have it eventually develop a neurodegenerative disease, such as Parkinsons disease, said study author John Peever, PhD, a U of T neuroscientist. […] „We showed that GABA and glycine shut off motor neurons during REM sleep and that’s what triggers REM paralysis,” said Peever. […] The data suggest the two neurotransmitters must both be present together to maintain motor control during sleep, rather than working separately. […] By identifying the neurotransmitters and receptors involved in sleep-related paralysis, this study points us to possible molecular targets for developing treatments for sleep-related motor disorders, which can often be debilitating, McGinty said.

• #66 Paralysis | Hemiplegia | MedlinePlus

  https://medlineplus.gov/paralysis.html

  Paralysis is the loss of muscle function in part of your body. It happens when something goes wrong with the way messages pass between your brain and muscles. Paralysis can be complete or partial. It can occur on one or both sides of your body. It can also occur in just one area, or it can be widespread. Paralysis of the lower half of your body, including both legs, is called paraplegia. Paralysis of the arms and legs is quadriplegia. […] Most paralysis is due to strokes or injuries such as spinal cord injury or a broken neck. Other causes of paralysis include: […] Nerve diseases such as amyotrophic lateral sclerosis […] Autoimmune diseases such as Guillain-Barre syndrome […] Bell’s palsy, which affects muscles in the face.

• #67 Paralysis of the cytotoxic granule machinery is a new cancer immune evasion mechanism mediated by chitinase 3-like-1 | Journal for ImmunoTherapy of Cancer

  https://jitc.bmj.com/content/9/11/e003224

  Paralysis of the cytotoxic granule machinery is a new cancer immune evasion mechanism mediated by chitinase 3-like-1. […] Natural killer (NK) cells require a functional lytic granule machinery to mediate effective antitumor responses. […] We demonstrate that recombinant CHI3L1 inhibits both ADCC and innate NK cell cytotoxicity. Mechanistically, CHI3L1 prevents the correct polarization of the microtubule-organizing center along with the lytic granules to the IS by hindering the receptor of advanced glycation end-products and its downstream JNK signaling. […] Our work highlights a new paradigm of tumor immune escape mediated by CHI3L1 which acts on the cytotoxic machinery and prevents granule polarization. […] Here, we show that CHI3L1 impairs NK cell cytotoxicity by limiting the polarization of lytic granules and inducing a dysfunctional IS.

• #68 Paralysis of the cytotoxic granule machinery is a new cancer immune evasion mechanism mediated by chitinase 3-like-1 | Journal for ImmunoTherapy of Cancer

  https://jitc.bmj.com/content/9/11/e003224

  Paralysis of the cytotoxic granule machinery is a new cancer immune evasion mechanism mediated by chitinase 3-like-1. […] Natural killer (NK) cells require a functional lytic granule machinery to mediate effective antitumor responses. […] We demonstrate that recombinant CHI3L1 inhibits both ADCC and innate NK cell cytotoxicity. Mechanistically, CHI3L1 prevents the correct polarization of the microtubule-organizing center along with the lytic granules to the IS by hindering the receptor of advanced glycation end-products and its downstream JNK signaling. […] Our work highlights a new paradigm of tumor immune escape mediated by CHI3L1 which acts on the cytotoxic machinery and prevents granule polarization. […] Here, we show that CHI3L1 impairs NK cell cytotoxicity by limiting the polarization of lytic granules and inducing a dysfunctional IS.

• #69 Paralysis of the cytotoxic granule machinery is a new cancer immune evasion mechanism mediated by chitinase 3-like-1 | Journal for ImmunoTherapy of Cancer

  https://jitc.bmj.com/content/9/11/e003224

  Paralysis of the cytotoxic granule machinery is a new cancer immune evasion mechanism mediated by chitinase 3-like-1. […] Natural killer (NK) cells require a functional lytic granule machinery to mediate effective antitumor responses. […] We demonstrate that recombinant CHI3L1 inhibits both ADCC and innate NK cell cytotoxicity. Mechanistically, CHI3L1 prevents the correct polarization of the microtubule-organizing center along with the lytic granules to the IS by hindering the receptor of advanced glycation end-products and its downstream JNK signaling. […] Our work highlights a new paradigm of tumor immune escape mediated by CHI3L1 which acts on the cytotoxic machinery and prevents granule polarization. […] Here, we show that CHI3L1 impairs NK cell cytotoxicity by limiting the polarization of lytic granules and inducing a dysfunctional IS.

• #70 Paralysis of the cytotoxic granule machinery is a new cancer immune evasion mechanism mediated by chitinase 3-like-1 | Journal for ImmunoTherapy of Cancer

  https://jitc.bmj.com/content/9/11/e003224

  The inhibitory effect exerted by CHI3L1 on both, ADCC and natural cytotoxicity of NK cells, was independent of modulating cytotoxicity receptors or the amount of degranulation. […] These results indicate that CHI3L1 does not affect the formation of the IS but inhibits the correct polarization of the MTOC and consequently of the lytic granules. […] Together, these results indicate that CHI3L1 binds to RAGE and acts as an inhibitor of its downstream JNK signaling, an essential step for MTOC polarization. […] Our data demonstrate a new role of CHI3L1 as a functionally distinct soluble immune checkpoint molecule that acts by impairing the cytotoxic machinery.

• #71 Paralysis of the cytotoxic granule machinery is a new cancer immune evasion mechanism mediated by chitinase 3-like-1 | Journal for ImmunoTherapy of Cancer

  https://jitc.bmj.com/content/9/11/e003224

  The inhibitory effect exerted by CHI3L1 on both, ADCC and natural cytotoxicity of NK cells, was independent of modulating cytotoxicity receptors or the amount of degranulation. […] These results indicate that CHI3L1 does not affect the formation of the IS but inhibits the correct polarization of the MTOC and consequently of the lytic granules. […] Together, these results indicate that CHI3L1 binds to RAGE and acts as an inhibitor of its downstream JNK signaling, an essential step for MTOC polarization. […] Our data demonstrate a new role of CHI3L1 as a functionally distinct soluble immune checkpoint molecule that acts by impairing the cytotoxic machinery.

• #72 Paralysis of the cytotoxic granule machinery is a new cancer immune evasion mechanism mediated by chitinase 3-like-1 | Journal for ImmunoTherapy of Cancer

  https://jitc.bmj.com/content/9/11/e003224

  The inhibitory effect exerted by CHI3L1 on both, ADCC and natural cytotoxicity of NK cells, was independent of modulating cytotoxicity receptors or the amount of degranulation. […] These results indicate that CHI3L1 does not affect the formation of the IS but inhibits the correct polarization of the MTOC and consequently of the lytic granules. […] Together, these results indicate that CHI3L1 binds to RAGE and acts as an inhibitor of its downstream JNK signaling, an essential step for MTOC polarization. […] Our data demonstrate a new role of CHI3L1 as a functionally distinct soluble immune checkpoint molecule that acts by impairing the cytotoxic machinery.

• #73 Paralysis of the cytotoxic granule machinery is a new cancer immune evasion mechanism mediated by chitinase 3-like-1 | Journal for ImmunoTherapy of Cancer

  https://jitc.bmj.com/content/9/11/e003224

  The inhibitory effect exerted by CHI3L1 on both, ADCC and natural cytotoxicity of NK cells, was independent of modulating cytotoxicity receptors or the amount of degranulation. […] These results indicate that CHI3L1 does not affect the formation of the IS but inhibits the correct polarization of the MTOC and consequently of the lytic granules. […] Together, these results indicate that CHI3L1 binds to RAGE and acts as an inhibitor of its downstream JNK signaling, an essential step for MTOC polarization. […] Our data demonstrate a new role of CHI3L1 as a functionally distinct soluble immune checkpoint molecule that acts by impairing the cytotoxic machinery.

• #74 Paralysis caused by “nagging” | The Medical Journal of Australia

  https://www.mja.com.au/journal/2007/187/6/paralysis-caused-nagging

  A woman in her 20s presented to the emergency department, malnourished and dehydrated, and with acute paralysis of the lower limbs. […] The nitrous oxide misuse combined with the malnutrition, with low vitamin B12 levels, apparently resulted in subacute combined degeneration of the spinal cord a rare complication of nitrous oxide misuse. […] Subacute combined degeneration of the spinal cord is a recognised complication of vitamin B12 deficiency or of nitrous oxide exposure (with or without pre-existing normal vitamin B12 levels). […] Nitrous oxide inhibits the active form of vitamin B12, rendering it unavailable to form the myelin sheath proteins, resulting in axonal swelling and eventual axonal loss. […] The mechanism of action is the inactivation of vitamin B12 (cobalamin) from its monovalent, active cobalt form (Co+) to the inactive, bivalent cobalt form (Co2+).

• #75 Paralysis caused by “nagging” | The Medical Journal of Australia

  https://www.mja.com.au/journal/2007/187/6/paralysis-caused-nagging

  A woman in her 20s presented to the emergency department, malnourished and dehydrated, and with acute paralysis of the lower limbs. […] The nitrous oxide misuse combined with the malnutrition, with low vitamin B12 levels, apparently resulted in subacute combined degeneration of the spinal cord a rare complication of nitrous oxide misuse. […] Subacute combined degeneration of the spinal cord is a recognised complication of vitamin B12 deficiency or of nitrous oxide exposure (with or without pre-existing normal vitamin B12 levels). […] Nitrous oxide inhibits the active form of vitamin B12, rendering it unavailable to form the myelin sheath proteins, resulting in axonal swelling and eventual axonal loss. […] The mechanism of action is the inactivation of vitamin B12 (cobalamin) from its monovalent, active cobalt form (Co+) to the inactive, bivalent cobalt form (Co2+).

• #76 Paralysis caused by “nagging” | The Medical Journal of Australia

  https://www.mja.com.au/journal/2007/187/6/paralysis-caused-nagging

  A woman in her 20s presented to the emergency department, malnourished and dehydrated, and with acute paralysis of the lower limbs. […] The nitrous oxide misuse combined with the malnutrition, with low vitamin B12 levels, apparently resulted in subacute combined degeneration of the spinal cord a rare complication of nitrous oxide misuse. […] Subacute combined degeneration of the spinal cord is a recognised complication of vitamin B12 deficiency or of nitrous oxide exposure (with or without pre-existing normal vitamin B12 levels). […] Nitrous oxide inhibits the active form of vitamin B12, rendering it unavailable to form the myelin sheath proteins, resulting in axonal swelling and eventual axonal loss. […] The mechanism of action is the inactivation of vitamin B12 (cobalamin) from its monovalent, active cobalt form (Co+) to the inactive, bivalent cobalt form (Co2+).

• #77 Paralysis caused by “nagging” | The Medical Journal of Australia

  https://www.mja.com.au/journal/2007/187/6/paralysis-caused-nagging

  The irreversibly inactivated vitamin B12 (Co2+) results in failure of methylation of proteins in the myelin sheaths and a loss of nerve cell axon integrity. […] Another contributing factor to the toxicity of nitrous oxide is the role of vitamin B12 as a cofactor of the methionine synthase reaction. […] Thus, nitrous oxide has a direct effect on DNA synthesis, as well as nerve axon integrity. […] The neuropathological changes observed in the affected spinal cord include initial swelling and irregularity of the myelin sheath surrounding the nerve cell axons (reversible), followed by frank demyelination and loss of axons (irreversible). […] A diagnosis of subacute combined degeneration of the spinal cord can be confirmed by MRI, in association with low serum vitamin B12 levels, but in some cases MRI scans show no abnormality. […] Treatment involves ceasing nitrous oxide use and giving vitamin B12 replacement therapy.

• #78 Paralysis caused by “nagging” | The Medical Journal of Australia

  https://www.mja.com.au/journal/2007/187/6/paralysis-caused-nagging

  The irreversibly inactivated vitamin B12 (Co2+) results in failure of methylation of proteins in the myelin sheaths and a loss of nerve cell axon integrity. […] Another contributing factor to the toxicity of nitrous oxide is the role of vitamin B12 as a cofactor of the methionine synthase reaction. […] Thus, nitrous oxide has a direct effect on DNA synthesis, as well as nerve axon integrity. […] The neuropathological changes observed in the affected spinal cord include initial swelling and irregularity of the myelin sheath surrounding the nerve cell axons (reversible), followed by frank demyelination and loss of axons (irreversible). […] A diagnosis of subacute combined degeneration of the spinal cord can be confirmed by MRI, in association with low serum vitamin B12 levels, but in some cases MRI scans show no abnormality. […] Treatment involves ceasing nitrous oxide use and giving vitamin B12 replacement therapy.

• #79 Paralysis caused by “nagging” | The Medical Journal of Australia

  https://www.mja.com.au/journal/2007/187/6/paralysis-caused-nagging

  The irreversibly inactivated vitamin B12 (Co2+) results in failure of methylation of proteins in the myelin sheaths and a loss of nerve cell axon integrity. […] Another contributing factor to the toxicity of nitrous oxide is the role of vitamin B12 as a cofactor of the methionine synthase reaction. […] Thus, nitrous oxide has a direct effect on DNA synthesis, as well as nerve axon integrity. […] The neuropathological changes observed in the affected spinal cord include initial swelling and irregularity of the myelin sheath surrounding the nerve cell axons (reversible), followed by frank demyelination and loss of axons (irreversible). […] A diagnosis of subacute combined degeneration of the spinal cord can be confirmed by MRI, in association with low serum vitamin B12 levels, but in some cases MRI scans show no abnormality. […] Treatment involves ceasing nitrous oxide use and giving vitamin B12 replacement therapy.

• #80 Paralysis caused by “nagging” | The Medical Journal of Australia

  https://www.mja.com.au/journal/2007/187/6/paralysis-caused-nagging

  The irreversibly inactivated vitamin B12 (Co2+) results in failure of methylation of proteins in the myelin sheaths and a loss of nerve cell axon integrity. […] Another contributing factor to the toxicity of nitrous oxide is the role of vitamin B12 as a cofactor of the methionine synthase reaction. […] Thus, nitrous oxide has a direct effect on DNA synthesis, as well as nerve axon integrity. […] The neuropathological changes observed in the affected spinal cord include initial swelling and irregularity of the myelin sheath surrounding the nerve cell axons (reversible), followed by frank demyelination and loss of axons (irreversible). […] A diagnosis of subacute combined degeneration of the spinal cord can be confirmed by MRI, in association with low serum vitamin B12 levels, but in some cases MRI scans show no abnormality. […] Treatment involves ceasing nitrous oxide use and giving vitamin B12 replacement therapy.

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