Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917801 (insomnia)
 10,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Isaacs' syndrome is an antibody-mediated potassium channel disorder. Clinical symptoms of Isaacs' syndrome are characterized by muscle cramp, slow relaxation following muscle contraction, and hyperhidrosis. Hyperexcitability of the peripheral nerve cause these symptoms, which are relieved by administration of Na channel blockers and immunotherapy.The target channel proteins are voltage-gated potassium channels (VGKCs). The suppression of voltage-gated outward K(+) current by antibodies induces hyperexcitability of the peripheral nerve. Electrophysiological findings show that antibodies may not directly block the kinetics of VGKCs, but may decrease channel density. From the electrophysiological, pharmacologic and immunologic view points, the site of origin of spontaneous discharges is located principally in the distal portion of the motor nerve."VGKC antibodies" are also detected in Morvan syndrome (severe insomnia with neuromyotonia and various autonomic disorders) and in a form of autoimmune limbic encephalitis. Recent studies indicated that the "VGKC antibodies" are mainly directed toward associated proteins (for example LGI-1, CASPR-2) that complex with VGKCs themselves. The "VGKC antibodies" are now usually known as VGKC-complex antibodies. In general, LGI-1 antibodies are most common in limbic encephalitis with SIADH. CASPR-2 antibodies are present in the majority of patients with Morvan syndrome.
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PMID:[Isaacs's syndrome and associated diseases]. 2429 81

Voltage-gated potassium channel (VGKC) complex antibodies are auto-antibodies, initially identified in acquired neuromyotonia (aNMT; Isaacs' syndrome), which cause muscle cramps and difficulty in opening the palm of the hands. Subsequently, these antibodies were found in patients presenting with aNMT along with psychosis, insomnia, and dysautonomia, collectively termed Morvan's syndrome (MoS), and in a limbic encephalopathy (LE) patient with prominent amnesia and frequent seizures. Typical LE cases have a distinctive adult-onset, frequent, brief dystonic seizure semiology that predominantly affects the arms and ipsilateral face. It has now been termed faciobrachial dystonic seizures (FBDS). The VGKC complex is a group of proteins that are strongly associated in situ and after extraction in the mild detergent digitonin. Recent studies indicated that the VGKC complex antibodies are mainly directed toward associated proteins (for example LGI1, Caspr2) that complex with VGKCs themselves. Patients with aNMT or MoS are most likely to have Caspr2 antibodies, whereas LGI1 antibodies are found characteristically in patients with FBDS and LE. We systematically identified and quantified autoantibodies in patient sera with VGKC-complex antibody associated encephalopathy and showed the relationship between individual antibodies and patient's symptoms. Furthermore, we revealed how autoantibodies disrupt the physiological functions of target proteins. LGI1 antibodies neutralize the interaction between LGI1 and ADAM22, reducing the synaptic AMPA receptors.
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PMID:[Voltage-Gated Potassium Channel-Complex Antibodies Associated Encephalopathy and Related Diseases]. 2766 87

Chronic kidney disease (CKD) predisposes one to either deficiency or toxic excess of different micronutrients. The knowledge on micronutrients-specifically water-soluble vitamins and trace elements-in CKD is very limited. Consequently, current guidelines and recommendations are mostly based on expert opinions or poor-quality evidence. Abnormalities of micronutrient resources in CKD develop for several reasons. Dietary restrictions and anorexia lead to an insufficient micronutrient intake, while diuretics use and renal replacement therapy lead to their excessive losses. Absorption is unpredictable, and metabolism impaired. Better understanding of the micronutrient needs of CKD patients could have an impact on many complications linked to vitamin and trace element disorders, including high mortality, increased risk of atherosclerosis, inflammation, oxidative stress, anemia, polyneuropathy, encephalopathy, weakness and fragility, muscle cramps, bone disease, depression, or insomnia. Here, we summarize the up-to-date knowledge on micronutrient resources in different stages of CKD, and share our experience with the assessment of micronutrient status.
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PMID:Vitamins and Microelement Bioavailability in Different Stages of Chronic Kidney Disease. 2829 76

Opioids are one of the commonly abused substances in India. Opioid withdrawal symptoms classically include severe muscle cramps, bone aches, autonomic symptoms, anxiety, restlessness, insomnia, and temperature dysregulation. However, reports of cases with delirium during withdrawal are few. A 25-year-old male with severe opioid withdrawal symptoms developed delirium. Investigations were normal. There were no comorbidities, no significant past history and family history. Patient treated for opioid dependence with tapering doses of lorazepam and clonidine. He was discharged with naltrexone. Patient lapsed 3 months later with similar presentation. Complications such as convulsions and delirium are recognized in alcohol withdrawal. However, these are rare as a feature of opioid withdrawal. This case illustrates the need for psychiatrists and physicians to be aware of the possibilities of delirium with opioid withdrawal and monitoring for the same is important because of its complications.
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PMID:A Rare Case of Complicated Opioid Withdrawal in Delirium Without Convulsions. 2851 58

Voltage-gated potassium channel (VGKC) complex auto-antibodies were initially identified in Isaacs' syndrome (IS), which is characterized by muscle cramps and neuromyotonia. These antibodies were subsequently identified in patients with Morvan's syndrome (MoS), which includes IS in conjunction with psychosis, insomnia, and dysautonomia. The antibodies have also been detected in a patient with limbic encephalopathy (LE) presenting with prominent amnesia and frequent seizures. Typical cases of LE have adult-onset, with frequent, brief dystonic seizures that predominantly affect the arms and ipsilateral face, and has recently been termed faciobrachial dystonic seizures. Autoantibodies against the extracellular domains of VGKC complex proteins, leucine-rich glioma-inactivated 1 (LGI1), and contactin-associated protein-2 (Caspr2), occur in patients with IS, MoS, and LE. However, routine testing has detected VGKC complex antibodies without LGI1 or Caspr2 reactivities (double-negative) in patients with other diseases, such as Creutzfeldt-Jakob disease and amyotrophic lateral sclerosis. Furthermore, double-negative VGKC complex antibodies are often directed against cytosolic epitopes of Kv1 subunits. Therefore, these antibodies should no longer be classified as neuronal-surface antibodies and lacking pathogenic potential. Novel information has been generated regarding autoantibody disruption of the physiological functions of target proteins. LGI1 antibodies neutralize the interaction between LGI1 and ADAM22, thereby reducing the synaptic AMPA receptors. It may be that the main action is on inhibitory neurons, explaining why the loss of AMPA receptors causes amnesia, neuronal excitability and seizures.
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PMID:[Current Perspective on Voltage-gated Potassium Channel Complex Antibody Associated Diseases]. 2963 80

Individuals receiving in-center maintenance hemodialysis bear a high burden of both physical and mood symptoms. More than half of patients on hemodialysis report sleep disturbance, muscle cramps, and fatigue. Patients describe symptoms as having a deleterious effect on their quality of life, suggesting that symptom alleviation may meaningfully improve patient-reported outcomes. Moreover, patients on hemodialysis have identified symptom management as a key area for research and innovation, prioritizing symptom alleviation over other health outcomes such as mortality and biochemical indices. Despite the importance of symptoms to patients, there has been little research explicitly geared toward improving patient symptoms, and therefore minimal innovation in symptom management. In general, the physiologic underpinnings of symptoms are poorly understood, hampering the development of targeted therapies. In fact, there have been few drugs or devices approved by the US Food and Drug Administration for the indication of improving any patient-reported outcomes for patients on hemodialysis. Recognizing this gap in innovation, the Kidney Health Initiative, a public-private partnership between the American Society of Nephrology and US Food and Drug Administration, convened a workgroup to first prioritize symptoms for the development of therapeutic interventions, and then identify near-term actionable research goals for the prioritized physical symptoms of insomnia, muscle cramps, and fatigue. This paper summarizes the pathophysiology of the three prioritized symptoms, identifies key knowledge gaps, acknowledges factors that challenge development of new therapies, and offers the nephrology community actionable research goals for insomnia, muscle cramps, and fatigue.
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PMID:Fostering Innovation in Symptom Management among Hemodialysis Patients: Paths Forward for Insomnia, Muscle Cramps, and Fatigue. 3039 26

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

Hyponatremia can be asymptomatic or have a wide range of clinical presentations such as headaches, muscle cramps, nausea, seizures, coma, cerebral edema and may even result in death. Despite it has been suggested that duloxetine has a relatively less risk of hyponatraemia, the number of case reports are increasing. A 45- year old female patient with complaints of fear, anxiety, sleeplessness and headache was started on duloxetine (30 mg/day). In the first week of the treatment, she was admitted to the emergency service with dizziness, dry mouth, polyuria and polydipsia. She had to be transferred to the intensive care unit because of agitation, loss of consciousness and a generalized tonic-clonic seizure. Blood levels of Sodium (Na+), Potassium (K+) and Chlorine (Cl-) were, respectfully, 121 mmol/L, 2.7 mmol/L and 87 mmol/L. Brain imaging displayed cerebral edema. Electrolyte levels were regulated with saline infusions. Amitriptyline was initiated for the ongoing headache and anxiety. In outpatient visits, hyponatremia did not recur in the following 3 months. Low dose duloxetine was associated with severe hyponatremia signs and symptoms in an individual who was not previously considered as high risk for hyponatraemia. The patient's history did not reveal any complaints related to hyponatremia when she was treated with sertraline two years ago. Based on these, we discussed the risk factors for hyponatremia and risky antidepressant classes.
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PMID:Duloxetine Induced Hyponatremia. 3259 91

Donepezil (DPZ) is an acetylcholinesterase inhibitor used for the clinical treatment of mild cognitive impairment. However, DPZ has been reported to have adverse effects, including causing abnormal cardiac rhythm, insomnia, vomiting, and muscle cramps. However, the existence of these effects in subjects without Dementia is unknown. In this study, we use zebrafish to conduct a deeper analysis of the potential adverse effects of DPZ on the short-term memory and behaviors of normal zebrafish by performing multiple behavioral and biochemical assays. Adult zebrafish were exposed to 1 ppm and 2.5 ppm of DPZ. From the results, DPZ caused a slight improvement in the short-term memory of zebrafish and induced significant elevation in aggressiveness, while the novel tank and shoaling tests revealed anxiolytic-like behavior to be caused by DPZ. Furthermore, zebrafish circadian locomotor activity displayed a higher reduction of locomotion and abnormal movement orientation in both low- and high-dose groups, compared to the control group. Biomarker assays revealed that these alterations were associated with an elevation of oxytocin and a reduction of cortisol levels in the brain. Moreover, the significant increases in reactive oxygen species (ROS) and malondialdehyde (MDA) levels in muscle tissue suggest DPZ exposure induced muscle tissue oxidative stress and muscle weakness, which may underlie the locomotor activity impairment. In conclusion, we show, for the first time, that chronic waterborne exposure to DPZ can severely induce adverse effects on normal zebrafish in a dose-dependent manner. These unexpected adverse effects on behavioral alteration should be carefully addressed in future studies considering DPZ conducted on zebrafish or other animals.
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PMID:Evaluation of the Adverse Effects of Chronic Exposure to Donepezil (An Acetylcholinesterase Inhibitor) in Adult Zebrafish by Behavioral and Biochemical Assessments. 3296 60


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