Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0013362 (dysarthria)
 3,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Autonomic dysfunction, neuropsychiatric problems, axial signs and sleep disorders are common complications of advanced Parkinson's disease (PD). Urinary disturbance due to detrusor hyperreflexia and iatrogenic orthostatic hypotension are prominent dysautonomic signs. Depression and anxiety are frequent but can occur exclusively during off periods. A fronto-sub cortical dementia occurs in 30% of PD patients, but anti-parkinsoniens drugs (APD) can cause hallucinations even in non demented PD patients. Axial signs, such as freezing, postural instabily or dysarthria become doparesistant. Insomnia, REM sleep disorders. At least, pain is very frequent. Exact analysis of these signs is important for an adequate treatement: most of them are improved by APD but some of them, like orthostatic hypotension or hallucinations, are increased by these drugs.
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PMID:[Other symptoms of advanced stage Parkinson's disease]. 1091 48

A 60-year-old man who has suffered dysarthria since 1999. He had noticed twitching of right upper extremity and orbicularis oris muscle since August 2000. The bulbar type of amyotrophic lateral sclerosis was diagnosed. He was admitted for evaluation of sleep disorder with respiratory distress on November 20, 2000. Arterial blood gas analysis on admission showed marked hypercapnea (PaCO2:51.6 Torr). Nocturnal hypoxia index, which was calculated using the nocturnal oximetry monitoring, was elevated. Non-invasive positive pressure ventilation started during sleep at night, although it was earlier than to start for mechanical ventilation. After one week, both hypercapnea and his nocturnal hypoxia index, together with symptoms, improved markedly. Respiratory insufficiency due to progressive fatigue of respiratory muscles, such as diaphragm and intercostal muscles, is a major cause of death in amyotrophic lateral sclerosis. In general mechanical ventilation is introduced when marked hypercapnea and dyspnea become clinically overt. However, the exact time to introduce noninvasive methods of ventilatory support for amyotrophic lateral sclerosis has not been established. Based on the observation in this patient, we would suggest that earlier introduction of non-invasive mechanical support for ventilation (nocturnal hypoxia index > 70) would be useful to improve the symptoms and to prolong the life of patients with ALS. The nocturnal hypoxia index is useful to decide the time of the introduction of non-invasive mechanical support for ventilation.
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PMID:[Early treatment with non-invasive positive pressure ventilation a successful case of bulbar type amyotrophic lateral sclerosis]. 1177 29

Alexander disease (AD) in its typical form is an infantile lethal leucodystrophy, characterized pathologically by Rosenthal fibre accumulation. Following the identification of glial fibrillary acidic protein (GFAP) gene as the causative gene, cases of adult-onset AD (AOAD) are being described with increasing frequency. AOAD has a different clinical and neuroradiological presentation with respect to early-onset AD, as abnormalities are mainly concentrated in the brainstem-spinal cord junction. We report detailed clinical and genetic data of 11 cases of AOAD, observed over a 4-year period, and a review of the previously reported 25 cases of genetically confirmed AOAD. In our series, onset occurred as late as age 62, and up to 71 in an affected deceased relative. Most cases appeared sporadic, but family history may be misleading. The most frequent symptoms were related to bulbar dysfunction-with dysarthria, dysphagia, dysphonia (seven patients)-, pyramidal involvement (seven patients) and cerebellar ataxia (seven patients). Four patients had palatal myoclonus. Sleep disorders were also observed (four cases). Bulbar symptoms, however, were infrequent at onset and two symptomatic patients had an almost pure pyramidal involvement. Two subjects were asymptomatic. Misdiagnosis at presentation was frequent and MRI was instrumental in suggesting the correct diagnosis by showing, in all cases, mild to severe atrophy of the medulla oblongata extending caudally to the cervical spinal cord. In ten patients, molecular studies revealed six novel missense mutations and three previously reported changes in GFAP. The last typical patient carried no definitely pathogenic mutation, but a missense variant (p.D157N), supposedly a rare polymorphism. Revision of the literature and the present series indicate that the clinical picture is not specific, but AOAD must be considered in patients of any age with lower brainstem signs. When present, palatal myoclonus is strongly suggestive. Pyramidal involvement, cerebellar ataxia and urinary disturbances are common. Less frequent findings include sleep disorders and dysautonomia. Fluctuations may occur. The course is variable, usually slowly progressive and less severe than the AD forms with earlier onset. AOAD is more common than previously thought and might even be the most common form of AD. The diagnosis is strongly suggested by MRI and confirmed by GFAP gene analysis.
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PMID:Adult-onset Alexander disease: a series of eleven unrelated cases with review of the literature. 1868 70

No validated biomarker is yet available for Parkinson's disease (PD). Clinical PD symptoms include dopa-responsive motor symptoms and dopa-resistant non motor symptoms. Some of the non motor symptoms begin during the premotor stage, like constipation, hyposmia or REM-sleep disorders. Dementia, gait disorders and dysarthria occur in later stages of the disease. PD pathology extends well beyond the substantia nigra. It affects autonomic and non autonomic nuclei in the brainstem and in the medulla, the olfactory bulb and the peripheral autonomic nervous system. Alpha-synuclein aggregates, called Lewy bodies and Lewy neurites, are detectable in these structures at early stages. The study of the enteric nervous system (ENS) displays the Lewy pathology in living patients through the digestive biopsies. Minor salivary glands analysis could be a good marker as well, but this needs confirmation. An anatomopathologic PD biomarker would be interesting at different stages of PD: for the positive diagnosis, to follow the progression and to develop neuroprotective treatments.
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PMID:[Autonomic nervous system as a source of biomarkers in Parkinson's disease]. 2228 42