Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026838 (spasticity)
 6,471 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The development of neuroprotective agents for the prevention of neuronal loss in acute conditions such as stroke and epilepsy or chronic neurodegenerative disorders including Parkinson's disease, Alzheimer's disease, Huntington's chorea, and motor neuron disease is currently focusing on drugs that inhibit excitatory amino acid neurotransmission or exhibit antioxidant properties. Unfortunately, potent antagonists at the N-methyl-D-aspartate (NMDA) type glutamate receptor, which is thought to mediate excitotoxic neuronal injury, e.g., MK-801 or phencyclidine (PCP), share a high probability of inducing psychotomimetic side effects. Further, these drugs have been associated with acute neurotoxicity in vitro and in vivo, precluding their clinical use. In contrast, low affinity NMDA receptor antagonists like amantadine and its dimethyl derivative, memantine, have been administered clinically for the management of Parkinson's disease, dementia, neuroleptic drug-induced side effects, and spasticity. These agents have only rarely induced significant psychotomimetic side effects. Recent pharmacologic advances have helped to elucidate how high drug affinity for the PCP binding site of the NMDA receptor may enhance psychotogenicity. Low affinity and associated fast voltage-dependent channel unblocking kinetics are likely to be responsible for the better tolerance of amantadine and memantine compared with MK-801 and PCP. Further factors apparently modulating psychotogenicity of glutamate receptor antagonists include differential actions on neuronal populations in various brain regions and interactions with neurotransmitter receptors other than the NMDA type glutamate receptor.
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PMID:Psychotogenicity and N-methyl-D-aspartate receptor antagonism: implications for neuroprotective pharmacotherapy. 901 83

Motor neurone disease is a rapidly progressive neurodegenerative disorder, characterized by muscular weakness and wasting with fasciculation and by spasticity. While most cases are sporadic, approximately 10% are inherited in an autosomal dominant mode. Recently, mutations in the gene encoding the free-radical scavenging enzyme superoxide dismutase-1 have been found to segregate with the disorder in 20% of familial cases. This is an exciting development, as free radical damage has long been implicated in the pathogenesis of motor neurone disease and it raises the possibility of novel therapeutic approaches in this otherwise fatal condition.
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PMID:Mechanisms in motor neurone disease: clues from genetic studies. 941 57

Amyotrophic lateral sclerosis (ALS) is a motor neuron disease with evidence of both anterior horn cell and corticospinal tract degeneration. The incidence of ALS is 1 to 2.5 cases per 100,000 population and the disease occurs primarily in adult life. The etiology of sporadic ALS remains unknown, although 5 to 10% of cases are familial. The diagnosis of ALS requires the presence of both upper and lower motor neuron findings and progressive motor dysfunction. Several theories regarding the pathogenesis of ALS have emerged including glutamate excitotoxicity, free radical oxidative stress, neurofilament accumulation, and autoimmunity. Clinical trials involving antiglutamate agents, antioxidants, immunosuppressants, and growth factors have shown no substantial benefit in slowing progression, with death usually occurring 2 to 5 years following the onset of symptoms. The management of ALS patients requires a multidisciplinary team that can provide the numerous medical and physical interventions necessary to treat weakness and fatigue, bulbar dysfunction, spasticity and pain, depression, and respiratory failure.
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PMID:Amyotrophic lateral sclerosis. 956 65

The autopsy findings of a 78-year-old man mimicking primary lateral sclerosis (PLS) are reported. He showed slowly progressive spasticity, pseudobulbar palsy and character change, and died 32 months after the onset of symptoms. Autopsy revealed severe atrophy of the frontal and temporal lobes, remarkable neuronal loss and gliosis in the precentral gyrus, left temporal lobe pole and amygdala, mild degeneration of the Ammon's horn, degeneration of the corticospinal tract, and very mild involvement of the lower motor neurons. The anterior horn cells only occasionally demonstrated Bunina body by cystatin-C staining, and skein-like inclusions by ubiquitin staining. This is a peculiar case with concomitant involvement in the motor cortex and temporal lobe in motor neuron disease predominantly affecting the upper motor neuron.
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PMID:Upper motor neuron predominant degeneration with frontal and temporal lobe atrophy. 982 19

Spastic paretic stiff-legged gait is a frequently encountered gait problem in patients with traumatic brain injury, as well as in many other patients with upper motor neuron disease. Formerly, spasticity of the quadriceps was considered to be the sole cause of stiff-legged gait. Quantitative gait analysis, however, may implicate hip flexor weakness or poor ankle mechanics as the cause of stiff-legged gait. We discuss the use of an algorithm to evaluate stiff-legged gait in traumatic brain injury using a quantitative gait analysis system such that the specific etiology of stiff-legged gait can be identified and can serve as the basis of a treatment plan.
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PMID:An algorithm to assess stiff-legged gait in traumatic brain injury. 1019 72

Adult motor neuron disease (amyotrophic lateral sclerosis [ALS]) is a neurodegenerative disorder characterized by loss of motor neurons in the cortex, brain stem, and spinal cord, manifested by upper and lower motor neuron signs and symptoms affecting bulbar, limb, and respiratory musculature. Clinically, the disease course is characterized by progressive weakness, atrophy, spasticity, dysarthria, dysphagia, and respiratory compromise, ultimately resulting in death or mechanical ventilation in the vast majority of patients. Patterns of presentation and pathological features of the disease, along with clinical and electrophysiologic criteria for diagnosis, are discussed in this review. Since 8% to 22% of patients survive more than 10 years without ventilator use, meticulous medical and rehabilitation management is extremely important to ensure optimal health and quality of life in these patients. Major issues in the care of individuals with ALS include weakness and spasticity, impairments in activities of daily living and mobility, communication deficits and dysphagia in those with bulbar involvement, respiratory compromise, fatigue and sleep disorders, pain, and psychosocial distress. Research in ALS changes rapidly, but is currently focused on potential etiologic factors such as glutamate excitotoxicity, role of oxidative stress, autoimmunity to calcium channels, and cytoskeletal abnormalities, as well as related treatment initiatives including glutamate modulators, neurotrophic factors, antioxidants, antiapoptotic factors, and gene therapy. Recently, mutations in the gene encoding Cu/Zn superoxide dismutase were identified in a subset of familial ALS patients. Riluzole, a glutamate antagonist and Na-channel blocker, became the only drug currently approved for treatment of ALS after studies showed a small positive effect on survival. Until a definitive treatment or cure for ALS is found, the multifaceted rehabilitation team approach remains the best hope for improving health and survival in this devastating illness.
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PMID:Evaluation and rehabilitation of patients with adult motor neuron disease. 1045 74

Hermann from Reichenau--Hermannus contractus--apparently suffered from a disease which led to considerable physical handicap leaving his outstanding intellectual talents undamaged. Various statements about his condition--an epileptic, suffering from spasticity, afflicted by poliomyelits--have never been reconsidered. Using the biography written by this disciple Berthold, the most important contemporary source about Hermanns' life, an approach to a correct diagnosis from a neurologists point of view was the aim of this study. By unbiased analysis of the symptoms described by Berthold a neurologic syndrome is worked out: it comprised a flaccid tetraparesis involving the bulbar area. The sensory as well as the autonomic nervous system were apparently not involved. Intellectual functions were unaffected. Considering this syndrome and other details of Hermanns' life as well as the beginning and course of his illness, a traumatic birth injury, an early childhood disease and a central nervous as well as an infectious disease are ruled out. Muscle disease is considered possible, but motor neuron disease--either amyotrophic lateral sclerosis or spinal muscular atrophy--seems to be the most convincing diagnosis.
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PMID:[Thoughts on the illness of Hermann von Reichenau (1019-1054)]. 1070 10

Primary lateral sclerosis as a nosological entity distinct from amyotrophic lateral sclerosis has been the subject of controversy since it was first described in the nineteenth century. Primary lateral sclerosis has been defined as a rare, non-hereditary disease characterized by highly progressive spinobulbar spasticity, related to the exclusive loss of precentral pyramidal neurons, with secondary pyramidal tract degeneration and preservation of anterior horn motor neurons. We carried out a study in nine patients with a diagnosis of primary lateral sclerosis. Our clinical, electrophysiological and pathological investigations provide evidence that the disease has a heterogeneous clinical presentation and that degeneration is not restricted to the central motor system but also affects the lower motor neuron. In view of this similarity with amyotrophic lateral sclerosis, primary lateral sclerosis may represent a slowly progressive syndrome closely related to motor neuron disease and amyotrophic lateral sclerosis.
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PMID:[What's new in primary lateral sclerosis?]. 1079 13

Amyotrophic lateral sclerosis (ALS) is the most common form of degenerative motor neuron disease in adulthood. The clinical picture was accurately described by Charcot over 125 years ago and consists of generalized fasciculations, progressive atrophy and weakness of the skeletal muscles, spasticity and pyramidal tract signs, dysarthria, dysphagia, and dyspnea. Pseudobulbar affect is common. Disease-specific treatment options are still unsatisfactory. However, therapeutic nihilism is not justified as a large array of palliative measures is available to enhance the quality of life of patients and their families. Palliative care in ALS is a multidisciplinary effort requiring careful coordination. An open and frank disclosure of the diagnosis is of paramount importance. Nutritional deficiency due to pronounced dysphagia can be relieved by a percutaneous endoscopic gastrostomy. Respiratory insufficiency can be effectively treated by noninvasive home mechanical ventilation. The terminal phase of the disease should be discussed, at the latest, when symptoms of dyspnea appear in order to prevent unwarranted fears of "choking to death." Collaboration with hospice and completion of advance directives can be of invaluable help in the terminal phase.
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PMID:Clinical characteristics and management of ALS. 1144 24

Amyotrophic lateral sclerosis (ALS) is the most common degenerative motor neuron disease in adults. The clinical picture consists of generalized fasciculations, progressive atrophy and weakness of the skeletal muscles, spasticity and pyramidal tract signs, dysarthria, dysphagia, and dyspnea. Pseudobulbar affect is common. Disease-specific treatment options are still unsatisfactory. Therapeutic nihilism is not justified as a large array of palliative measures available to enhance the quality of life of patients and their families. Because of its clinical characteristics, ALS represents a paradigm for palliative care in neurological diseases. Numerous projects are being undertaken worldwide in an effort to enlarge the evidence base for palliative interventions in ALS. Palliative care in ALS is a multidisciplinary effort requiring careful coordination. An open and empathic disclosure of the diagnosis is essential. Nutritional deficiency caused by dysphagia can be relieved by a percutaneous endoscopic gastrostomy. Respiratory insufficiency can be effectively treated by non-invasive home mechanical ventilation. The terminal phase of the disease should be discussed at the latest when symptoms of dyspnea appear, in order to prevent unwarranted fears of "choking to death." Psychological and spiritual care of patients and families are important. Collaboration with hospice institutions and completion of advance directives can be of invaluable help in the terminal phase.
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PMID:Palliative care in amyotrophic lateral sclerosis. 1185 2


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