Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011168 (dysphagia)
 15,644 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Botulinum toxin is a dreaded biological toxin elaborated by Clostridium botulinum. The action of this toxin is to cause paralysis of both voluntary and involuntary muscles. The unique property of paralysing capability of muscles has been used for the benefit of human beings. Dr Allan Scot, an ophthalmologist, first used the toxin in a patient with squint in 1981 and since then the botulinum toxin is being used in various disorders characterised by muscle overactivity such as spasticity in both children and adult, dystonic conditions such as blepharospasm, cervical dystonia, spasmodic dysphonia, writer's cramp, etc, hemifacial spasm and headache. Its main action is at the terminal nerve endings of myoneural junction and it prevents release of acetylcholine from vesicles thus causing chemical denervation. Its action persists for 3 to 4 months on an average. Its side effects such as drooping, diplopia, dysphagia, depending on the sites of injection, are few and usually transient. Generalised anaphylaxis is almost unknown. Now botulinum toxin is being used in non-neurological conditions where muscles are under spasmodic state such as achalasia cardia, anal fissure, spasm of urethral sphincter, etc. Because of wider safety range and fewer complications, botulinum toxin has been an important therapeutic armamentarium in different branches of medicine and surgery.
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PMID:Botulinum toxin: a dreaded toxin for use in human being. 1245 15

Patients with amyotrophic lateral sclerosis (ALS) have symptoms of progressive muscle weakness, of disturbed speech and swallowing, and in the terminal phase those of respiratory weakness. Treatment options, in particular those for excessive weight loss and respiratory weakness, should be introduced to the patients and their families when the patient is emotionally capable and before dysarthria severely hampers communication. Special equipment for keeping the patient as mobile as possible should be made available much earlier than in the case of other diseases of the muscles as in ALS progression is much faster. Cramps, pathological crying or laughter, spasms, and spasticity can all be treated by medication. When speech can no longer be understood, adaptive strategies such as sign language, mime, posture and communication apparatus varying from a note pad to advanced computer systems can be used. Sialorrhoea, caused by difficulty swallowing with its accompanying danger of aspiration can be halted by the use of medication, by radiotherapy and by the injection into the salivary glands of botulin A toxin. Weight loss, also a result of dysphagia, can be avoided by eating frequent small meals or if necessary performing a percutaneous endoscopic or radiological gastroscopy. Excess mucus in the respiratory tract can be treated with anticholinergics. Difficulty in coughing up thick and sticky mucus cannot always be adequately helped. Respiratory weakness is treatable by external respiratory supportive therapy using a nasal mask, as well as invasive respiratory support via a trachcostoma and by treating the symptoms of respiratory weakness. The latter form of treatment is palliative and forms part of terminal care. During the terminal phase restlessness, anxiety, pain, and dyspnoea require the most attention. Treatment requires careful multidisciplinary cooperation.
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PMID:[The symptomatic treatment of amyotrophic lateral sclerosis]. 1519 69

Botulinum toxin type B (BTX-B) has been approved by the Food and Drug Administration for the treatment of cervical dystonia. However, as with botulinum toxin type A (BTX-A) it has off-label uses, such as for hyperhidrosis, focal dystonias, spasticity, and facial wrinkles. BTX-B has also been shown to be a safe and effective alternative for patients who are resistant to BTX-A. The most commonly reported side effects include dry mouth and dysphagia. To date, there have been few reports of visual disturbances associated with BTX-B use. In this study, we report on three individual patients who received BTX-B and who subsequently developed parasympathetic dysfunction of the visual system after injections of BTX-B at remote sites.
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PMID:Visual system side effects caused by parasympathetic dysfunction after botulinum toxin type B injections. 1580 68

Primary lateral sclerosis (PLS) is a rare progressive paralytic disorder that results from dysfunction of the upper motoneurons. Although PLS is a sporadic disorder of adult middle age, it has also been described in children as juvenile PLS or JPLS. The causative gene for JPLS was found to be ALS2, which is also responsible for a recessive form of amyotrophic lateral sclerosis, for infantile onset ascending hereditary spastic paralysis (IAHSP) and for a form of complicated hereditary spastic paraplegia (cHSP). ALS2 gene encodes a protein termed alsin, containing multiple guanine nucleotide exchange factor domains, specifically binding to small GTPase Rab5 and acting as a GEF for Rab5. In vitrostudies performed with full-length and truncating forms of alsin protein support its role in endosomal dynamics and trafficking of mitochondria. All ALS2 mutations so far reported generate alsin protein truncation. Here, we describe the first homozygous missense mutation in ALS2, p.G540E. The mutation, which falls within the RCC1 domain, was identified in a 34-year-old patient with typical signs of JPLS such as ascending generalized and severe spasticity involving the limbs and the bulbar region, dysphagia, limb atrophy, preserved cognition and sensation. The father and two proband's sisters were found to be heterozygous carriers of the mutation with no signs of the disease. Studies in the neuronal cell line SK-N-BE indicated that the known subcellular localization of wild-type alsin with the early endosome antigen 1, in enlarged endosomal structures, and transferrin receptor is completely lost by the mutant protein, thus indicating that this mutation leads to protein delocalization. Mutant alsin induced neuronal death itself and also significantly enhanced the apoptogenic effect of NMDA and staurosporine. This effect was associated with decreased Bcl-xL : Bax ratio. In contrast, wild-type alsin was neuroprotective and increased Bcl-xL : Bax ratio. Our results provide the first demonstration that a missense mutation in alsin is cytotoxic. In addition, the identification of Bcl-xL/Bax as target of protection by alsin and of cytotoxicity by the mutant form provides a new signalling event regulated by alsin protein that may be important to define its role in neuronal physiology and neurodegeneration. Finally, the phenotype-genotype correlation in our patient, in view of all other ALS2 mutant cases reported previously, suggests a functional interplay of long and short forms of alsin in relation to disease onset and progression.
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PMID:The first ALS2 missense mutation associated with JPLS reveals new aspects of alsin biological function. 1667 Jan 79

Cervicothoracic kyphotic deformity may inhibit horizontal gaze function, impede activities of daily living, and induce disabling pain. Eventually, some patients develop a chin-on-chest deformity that limits their ability to eat and drink; in the end stage, a few patients also may have difficulty breathing. Progressive kyphosis can stretch the spinal cord leading to myelopathy with progressive lower extremity spasticity and weakness. Indications for surgery include myelopathy, pain, dysphagia or dyspnea owing to kyphosis, and difficulty maintaining a functional horizontal gaze. Patients with unstable cervicothoracic fractures also require surgical fixation. For these patients, surgical goals include deformity correction with restoration of an acceptable forward gaze, re-establishment of sagittal balance, decompression of the spinal cord (if myelopathic), and stable fixation.
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PMID:Cervicothoracic kyphosis. 1687 28

About 30% of patients with chronic upper motor neuron syndrome (UMNS) suffer from disabling spasticity-related pain not sufficiently correctable by conventional treatment. Delta9-tetrahydrocannabinol (Delta(9)-THC) was reported to add benefit in the treatment of pain in patients with multiple sclerosis (MS). The question arose whether synthetic cannabinoids with lower potential for psychotropic side effects could be effective as well. To evaluate the safety and efficacy of low dose treatment with the synthetic cannabinoid Nabilone (1 mg per day) on spasticity-related pain a placebo-controlled double-blind crossover trial was performed.11 out of 13 included patients completed the study. The 11-Point-Box-Test showed a significant decrease of pain under Nabilone (p < 0.05), while spasticity, motor function and activities of daily living did not change. 5 patients reported side effects: one moderate transient weakness of the lower limbs (Nabilone phase, drop out), three mild drowsiness (two Nabilone, one placebo) and one mild dysphagia (placebo). One patient was excluded from the study due to an acute relapse of multiple sclerosis (Nabilone phase, drop out). Nabilone 1 mg per day proved to be a safe and easily applicable option in the care of patients with chronic UMNS and spasticity-related pain otherwise not controllable.
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PMID:Low dose treatment with the synthetic cannabinoid Nabilone significantly reduces spasticity-related pain : a double-blind placebo-controlled cross-over trial. 1698 92

Many people with MS suffer from severe and disabling symptoms that restrict their social and private lives, and hence affect their quality of life; it is, therefore, essential that any symptoms that they experience are reduced effectively. Symptomatic treatment should also aim to prevent secondary complications that may result from existing disabilities. Since many MS patients are unaware that some of their complaints may be attributable to MS, e.g. fatigue, sexual dysfunction, pain or dysphagia, all patients should be thoroughly questioned about all healthcare issues and the results must be documented. In recent months, several studies about the treatment of important MS symptoms--like spasticity, pain, fatigue, bladder and sexual dysfunction, depression and cognitive impairment--have been published; this article will briefly summarize and discuss some of these treatments.
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PMID:What is new in symptom management? 1750 49

The case of a term, male neonate (birthweight 3785g) with cephalic presentation, Caesarean-section (C-section) delivery, and failure to thrive is reported. The infant presented with generalized hypotonia and respiratory failure immediately following birth. An initial diagnosis of hypoxic-ischemic encephalopathy was made. However, ventilator dependency and slow recovery of generalized tonus over the following weeks could not be explained. Late cervical magnetic resonance imaging showed extensive syringomyelia from C2 to C7. To the authors' knowledge, this is the first report of syringomyelia after a C-section delivery following cephalic presentation without any associated abnormalities. Follow-up at 2 years of age revealed no improvement on neurological examination: poor head control, difficulty swallowing, flaccid paralysis of upper limbs, and spasticity of lower limbs with exacerbated deep reflexes and spontaneous clonus. Difficulties in establishing the diagnosis and managing the case are discussed.
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PMID:Syringomyelia and chronic respiratory failure in a term infant delivered by Caesarean section. 1759 28

Digestive surgeons should form part of the multidisciplinary team managing patients with oropharyngeal dysphagia. These patients can be diagnosed through clinical methods and complementary investigations such as videofluoroscopy and pharyngoesophageal manometry. These techniques also allow specific treatment to be selected. Up to one-third of patients with dysphagia suffer from malnutrition as a result of alterations in food bolus transport. Furthermore, up to two-thirds show alterations in swallowing safety (penetrations and aspirations, especially when swallowing liquids), as well as a high risk of respiratory infections and aspiration pneumonia. Increasing food bolus viscosity to 3500-4000 mPas (pudding viscosity) improves the effectiveness of swallowing and reduces the risk of aspirations. Botulinic toxin injection in the upper esophageal sphincter is indicated in patients with spasticity of neuromuscular origin. Cricopharyngeal myotomy is the basis of treatment for Zenker's diverticulum and is also indicated in patients with alterations in the upper esophageal sphincter and preserved oropharyngeal motor response.
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PMID:[Diagnosis and treatment of functional oropharyngeal dysphagia. Features of interest to the digestive surgeon]. 1778 40

Deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT) activity is an inborn error of purine metabolism associated with uric acid overproduction and a continuum spectrum of neurological manifestations depending on the degree of the enzymatic deficiency. The prevalence is estimated at 1/380,000 live births in Canada, and 1/235,000 live births in Spain. Uric acid overproduction is present inall HPRT-deficient patients and is associated with lithiasis and gout. Neurological manifestations include severe action dystonia, choreoathetosis, ballismus, cognitive and attention deficit, and self-injurious behaviour. The most severe forms are known as Lesch-Nyhan syndrome (patients are normal at birth and diagnosis can be accomplished when psychomotor delay becomes apparent). Partial HPRT-deficient patients present these symptoms with a different intensity, and in the least severe forms symptoms may be unapparent. Megaloblastic anaemia is also associated with the disease. Inheritance of HPRT deficiency is X-linked recessive, thus males are generally affected and heterozygous female are carriers (usually asymptomatic). Human HPRT is encoded by a single structural gene on the long arm of the X chromosome at Xq26. To date, more than 300 disease-associated mutations in the HPRT1 gene have been identified. The diagnosis is based on clinical and biochemical findings (hyperuricemia and hyperuricosuria associated with psychomotor delay), and enzymatic (HPRT activity determination in haemolysate, intact erythrocytes or fibroblasts) and molecular tests. Molecular diagnosis allows faster and more accurate carrier and prenatal diagnosis. Prenatal diagnosis can be performed with amniotic cells obtained by amniocentesis at about 15-18 weeks' gestation, or chorionic villus cells obtained at about 10-12 weeks' gestation. Uric acid overproduction can be managed by allopurinol treatment. Doses must be carefully adjusted to avoid xanthine lithiasis. The lack of precise understanding of the neurological dysfunction has precluded development of useful therapies. Spasticity, when present, and dystonia can be managed with benzodiazepines and gamma-aminobutyric acid inhibitors such as baclofen. Physical rehabilitation, including management of dysarthria and dysphagia, special devices to enable hand control, appropriate walking aids, and a programme of posture management to prevent deformities are recommended. Self-injurious behaviour must be managed by a combination of physical restraints, behavioural and pharmaceutical treatments.
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PMID:Hypoxanthine-guanine phosophoribosyltransferase (HPRT) deficiency: Lesch-Nyhan syndrome. 1806 74


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