Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002736 (amyotrophic lateral sclerosis)
 19,048 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Parkinson's disease (PD) is classically defined as a motor disorder resulting from decreased dopamine production in the basal ganglia circuit. In an attempt to better diagnose and treat PD before the onset of severe motor dysfunction, recent attention has focused on the early, non-motor symptoms, which include but are not limited to sleep disorders such as excessive daytime sleepiness (EDS) and REM behavioral disorder (RBD). However, few animal models have been able to replicate both the motor and non-motor symptoms of PD. Here, we present a progressive rat model of parkinsonism that displays disturbances in sleep/wake patterns. Epidemiological studies elucidated a link between the Guamanian variant of Amyotrophic Lateral Sclerosis/Parkinsonism Dementia Complex (ALS/PDC) and the consumption of flour made from the washed seeds of the plant Cycas micronesica (cycad). Our study examined the effects of prolonged cycad consumption on sleep/wake activity in male, Sprague-Dawley rats. Cycad-fed rats exhibited an increase in length and/or number of bouts of rapid eye movement (REM) sleep and Non-REM (NREM) sleep at the expense of wakefulness during the active period when compared to control rats. This hypersomnolent behavior suggests an inability to maintain arousal. In addition, cycad-fed rats had significantly fewer orexin cells in the hypothalamus. Our results reveal a novel rodent model of parkinsonism that includes an EDS-like syndrome that may be associated with a dysregulation of orexin neurons. Further characterization of this early, non-motor symptom, may provide potential therapeutic interventions in the treatment of PD.
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PMID:Sleep alterations in an environmental neurotoxin-induced model of parkinsonism. 2071 46

Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease inevitably leading to generalized muscle weakness and premature death. Sleep disturbances are extremely common in patients with ALS and substantially add to the burden of disease for both patients and caregivers. Disruption of sleep can be caused by physical symptoms, such as muscle cramps, pain, reduced mobility, spasticity, mucus retention, and restless legs syndrome. In addition, depression and anxiety may lead to significant insomnia. In a small subset of patients, rapid eye movement (REM) sleep behavioral disorder may be present, reflecting neurodegeneration of central nervous system pathways which are involved in REM sleep regulation. With regard to overall prognosis, sleep-disordered breathing (SDB) and nocturnal hypoventilation (NH) are of utmost importance, particularly because NH precedes respiratory failure. Timely mechanical ventilation is one of the most significant therapeutic measures to prolong life span in ALS, and transcutaneous capnometry is superior to pulse oxymetry to detect NH early. In addition, it has been shown that in patients on home ventilatory support, survival time depends on whether normocapnia, normoxia, and elimination of apneic events during sleep can be reliably achieved. Several studies have investigated sleep patterns and clinical determinants of sleep disruption in ALS, but exact prevalence numbers are unknown. Thus, constant awareness for sleep-related symptoms is appropriate. Since no curative treatment can be offered to affected patients, sleep complaints should be thoroughly investigated in order to identify any treatable etiology and improve or stabilize quality of life as much as possible. The use of hypnotics should be confined to palliation during the terminal phase and refractory insomnia in earlier stages of the disease, taking into account that most compounds potentially aggravate SDB.
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PMID:Sleep disturbances in patients with amyotrophic lateral sclerosis: current perspectives. 3149 52

Rapid eye movement sleep behavior disorder (RBD) is a sleep behavior disorder characterized by abnormal behaviors and loss of muscle atonia during rapid eye movement (REM) sleep. RBD is generally considered to be associated with synucleinopathies, such as Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), and usually precedes years before the first symptom of these diseases. It is believed that RBD predicts the neurodegeneration in synucleinopathy. However, increasing evidences have shown that RBD is also found in non-synucleinopathy neurodegenerative diseases, including Alzheimer's disease (AD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), etc. Sleep disturbance such as RBD may be an early sign of neurodegeneration in these diseases, and also serve as an assessment of cognitive impairments. In this review, we updated the clinical characteristics, diagnosis, and possible mechanisms of RBD in neurogenerative diseases. A better understanding of RBD in these neurogenerative diseases will provide biomarkers and novel therapeutics for the early diagnosis and treatment of the diseases.
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PMID:Rapid Eye Movement Sleep Behavior Disorder and Neurodegenerative Diseases: An Update. 3225 44

Neuropsychiatric syndromes and symptoms play increasingly important roles in research diagnostic criteria for neurodegenerative disorders. Diagnostic criteria were reviewed including those for dementia, Alzheimer's disease, mild cognitive impairment, mild behavioral impairment, prodromal Alzheimer's disease, dementia with Lewy bodies, prodromal dementia with Lewy bodies, Parkinson's disease, multiple system atrophy, frontotemporal dementia, primary progressive aphasia, progressive supranuclear palsy, corticobasal degeneration, traumatic encephalopathy syndrome, Huntington' disease, amyotrophic lateral sclerorsis. All contemporary research diagnostic criteria for neurodegenerative disorders expect those for Parkinson's disease, primary progressive aphasia, multisystem atrophy and amyotrophic lateral sclerosis include neuropsychiatric phenomena as core diagnostic criteria. There are no disease-specific neuropsychiatric symptoms; apathy and disinhibition are common in tauopathies, and rapid-eye-movement sleep behavioral disorder occurs almost exclusively in synucleinopathies. Neuropsychiatric symptoms and syndromes are increasingly integrated into research diagnostic criteria for neurodegenerative disorders; they require clinician skills for recognition; their biology is better understood as their relationships to cognitive, motor, and autonomic symptoms of neurodegenerative disorders are studied.
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PMID:The Role of Neuropsychiatric Symptoms in Research Diagnostic Criteria for Neurodegenerative Diseases. 3281 25