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Orphanet Journal of Rare Diseases Jun 2019Satoyoshi syndrome is a multisystemic rare disease of unknown etiology, although an autoimmune basis is presumed. Its main symptoms are: painful muscle spasms, diarrhea,... (Review)
Review
BACKGROUND
Satoyoshi syndrome is a multisystemic rare disease of unknown etiology, although an autoimmune basis is presumed. Its main symptoms are: painful muscle spasms, diarrhea, alopecia and skeletal abnormalities. Clinical course without treatment may result in serious disability or death. A review of treatment and its response is still pending.
RESULTS
Sixty-four cases of Satoyoshi syndrome were published between 1967 and 2018. 47 cases described the treatment administered. Drugs used can be divided into two main groups of treatment: muscle relaxants/anticonvulsants, and corticosteroids/immunosuppressants. Dantrolene improved muscle symptoms in 13 out of 15 cases, but not any other symptoms of the disease. Other muscle relaxants or anticonvulsant drugs showed little or no effect. 28 out of 30 cases responded to a regimen that included costicosteroids. Other immunosuppressive drugs including cyclosporine, mycophenolate mofetil, azathioprine, methotrexate, tacrolimus and cyclophosphamide were used to decrease corticosteroid dose or improve efficacy. Immunoglobulin therapy was used in nine patients and four of them obtained a favorable response.
CONCLUSION
Corticosteroids was the most widely treatment employed with the best results in Satoyoshi syndrome. Further studies are needed to determine optimal dose and duration of corticosteroids as well as the role of other immunosuppressants and immunoglobulin therapy. Genetic or autoimmune markers will be useful to guide future therapies.
Topics: Adrenal Cortex Hormones; Alopecia; Animals; Anticonvulsants; Bone and Bones; Dantrolene; Diarrhea; Female; Humans; Immunization, Passive; Immunosuppressive Agents; Male; Rare Diseases; Spasm
PubMed: 31217029
DOI: 10.1186/s13023-019-1120-7 -
Anesthesiology Jan 2019Although dantrolene effectively treats malignant hyperthermia (MH), discrepant recommendations exist concerning dantrolene availability. Whereas Malignant Hyperthermia...
BACKGROUND
Although dantrolene effectively treats malignant hyperthermia (MH), discrepant recommendations exist concerning dantrolene availability. Whereas Malignant Hyperthermia Association of the United States guidelines state dantrolene must be available within 10 min of the decision to treat MH wherever volatile anesthetics or succinylcholine are administered, a Society for Ambulatory Anesthesia protocol permits Class B ambulatory facilities to stock succinylcholine for airway rescue without dantrolene. The authors investigated (1) succinylcholine use rates, including for airway rescue, in anesthetizing/sedating locations; (2) whether succinylcholine without volatile anesthetics triggers MH warranting dantrolene; and (3) the relationship between dantrolene administration and MH morbidity/mortality.
METHODS
The authors performed focused analyses of the Multicenter Perioperative Outcomes Group (2005 through 2016), North American MH Registry (2013 through 2016), and Anesthesia Closed Claims Project (1970 through 2014) databases, as well as a systematic literature review (1987 through 2017). The authors used difficult mask ventilation (grades III and IV) as a surrogate for airway rescue. MH experts judged dantrolene treatment. For MH morbidity/mortality analyses, the authors included U.S. and Canadian cases that were fulminant or scored 20 or higher on the clinical grading scale and in which volatile anesthetics or succinylcholine were given.
RESULTS
Among 6,368,356 queried outcomes cases, 246,904 (3.9%) received succinylcholine without volatile agents. Succinylcholine was used in 46% (n = 710) of grade IV mask ventilation cases (median dose, 100 mg, 1.2 mg/kg). Succinylcholine without volatile anesthetics triggered 24 MH cases, 13 requiring dantrolene. Among 310 anesthetic-triggered MH cases, morbidity was 20 to 37%. Treatment delay increased complications every 10 min, reaching 100% with a 50-min delay. Overall mortality was 1 to 10%; 15 U.S. patients died, including 4 after anesthetics in freestanding facilities.
CONCLUSIONS
Providers use succinylcholine commonly, including during difficult mask ventilation. Succinylcholine administered without volatile anesthetics may trigger MH events requiring dantrolene. Delayed dantrolene treatment increases the likelihood of MH complications. The data reported herein support stocking dantrolene wherever succinylcholine or volatile anesthetics may be used.
Topics: Humans; Dantrolene; Databases, Factual; Malignant Hyperthermia; Muscle Relaxants, Central; Neuromuscular Depolarizing Agents; Succinylcholine
PubMed: 30550426
DOI: 10.1097/ALN.0000000000002490 -
Frontiers in Physiology 2018Dementia has a significant impact on quality of life of older individuals. Impaired proteostasis has been implicated as a potential cause of dementia, that can be...
Dementia has a significant impact on quality of life of older individuals. Impaired proteostasis has been implicated as a potential cause of dementia, that can be therapeutically targeted to improve patient outcomes. This review aimed to collate all current evidence of the potential for targeting proteostasis with repurposed drugs as an intervention for age-related dementia and cognitive decline. PubMed, Web of Science and Embase databases were searched from inception until 4th July 2017 for studies published in English. Interventional studies of repurposed proteostasis-modifying drugs in Alzheimer's disease (AD), Parkinson's disease (PD), Lewy Body disease, vascular dementia, and cognitive aging, in either animal models or humans with change in cognition as the outcome were included. The SYRCLE and Cochrane tools were used to assess risk of bias for included studies. Overall 47 trials, 38 animal and 9 human, were isolated for inclusion in this review. Drugs tested in animals and humans included lithium, rapamycin, rifampicin, and tyrosine kinase inhibitors. Drugs tested only in animals included Macrophage and Granulocyte-Macrophage Colony Stimulating Factors, methylene blue, dantrolene, geranylgeranylacetone, minocycline and phenylbutyric acid. Lithium ( = 10 animal, = 6 human) and rapamycin ( = 12 animal, = 1 human) were the most studied proteostasis modifying drugs influencing cognition. Nine of ten animal studies of lithium showed a statistically significant benefit in Alzheimer's models. Rapamycin demonstrated a significant benefit in models of vascular dementia, aging, and Alzheimer's, but may not be effective in treating established Alzheimer's pathology. Lithium and nilotinib had positive outcomes in human studies including Alzheimer's and Parkinson's patients respectively, while a human study of rifampicin in Alzheimer's failed to demonstrate benefit. Microdose lithium showed a strongly significant benefit in both animals and humans. While the risk of bias was relatively low in human studies, the risk of bias in animal studies was largely unclear. Overall, the collective findings support the hypothesis that targeting proteostasis for treatment of dementia may be beneficial, and therefore future studies in humans with repurposed proteostasis modifying drugs are warranted. Larger human clinical trials focusing on safety, efficacy, tolerability, and reproducibility are required to translate these therapeutics into clinical practice.
PubMed: 30425653
DOI: 10.3389/fphys.2018.01520 -
Developmental Medicine and Child... Dec 2017To evaluate the actual evidence of efficacy of oral pharmacological treatments in the management of dyskinetic cerebral palsy (CP). (Review)
Review
AIM
To evaluate the actual evidence of efficacy of oral pharmacological treatments in the management of dyskinetic cerebral palsy (CP).
METHOD
A systematic review was performed according to the American Academy for Cerebral Palsy and Developmental Medicine (AACPDM) and Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology. Articles were searched for in PubMed/MEDLINE, Scopus, Web of Science, Cochrane Library, Database of Reviews of Effectiveness, OTSeeker, Physiotherapy Evidence Database, REHABDATA, and ClinicalTrials.gov.
RESULTS
Sixteen articles met the eligibility criteria. Eight studies on trihexyphenidyl and two on levodopa showed contradictory results. Low efficacy was reported for diazepam, dantrolene sodium, perphenazine, and etybenzatropine. Tetrabenazine, gabapentin and levetiracetam should be studied in more detail. The updated available evidence does not support any therapeutic algorithm for the management of dyskinetic CP.
INTERPRETATION
This lack of evidence is partially owing to the inconsistency of classifications of patients and of outcome measures used in the reviewed studies. Further randomized, double-blind, placebo-controlled pharmacological trials, optimized for different age groups, based on valid, reliable, and disease-specific rating scales are strongly needed. Outcome measures should be selected within the framework of the International Classification of Functioning, Disability and Health.
WHAT THIS PAPER ADDS
Evidence to prove (or disprove) the efficacy of oral drugs in dyskinetic cerebral palsy is low. The most investigated drugs, trihexyphenidyl and levodopa, show contradictory results. Tetrabenazine, levetiracetam, and gabapentin efficacy should be studied in more detail. Lack of evidence is partially due to the inconsistency of classifications and outcome measures used. Outcome measures should be selected within the framework of the International Classification of Functioning, Disability and Health in next clinical trials.
Topics: Anticonvulsants; Cerebral Palsy; Dyskinesias; Humans; Neurotransmitter Agents; Outcome Assessment, Health Care
PubMed: 28872668
DOI: 10.1111/dmcn.13532 -
The Cochrane Database of Systematic... Nov 2014Background McArdle disease (Glycogen Storage Disease type V) is caused by an absence of muscle phosphorylase leading to exercise intolerance,myoglobinuria rhabdomyolysis... (Meta-Analysis)
Meta-Analysis Review
Background McArdle disease (Glycogen Storage Disease type V) is caused by an absence of muscle phosphorylase leading to exercise intolerance,myoglobinuria rhabdomyolysis and acute renal failure. This is an update of a review first published in 2004.Objectives To review systematically the evidence from randomised controlled trials (RCTs) of pharmacological or nutritional treatments for improving exercise performance and quality of life in McArdle disease.Search methods We searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE and EMBASE on 11 August 2014.Selection criteria We included RCTs (including cross-over studies) and quasi-RCTs. We included unblinded open trials and individual patient studies in the discussion. Interventions included any pharmacological agent or nutritional supplement. Primary outcome measures included any objective assessment of exercise endurance (for example aerobic capacity (VO2) max, walking speed, muscle force or power and fatigability). Secondary outcome measures included metabolic changes (such as reduced plasma creatine kinase and a reduction in the frequency of myoglobinuria), subjective measures (including quality of life scores and indices of disability) and serious adverse events.Data collection and analysis Three review authors checked the titles and abstracts identified by the search and reviewed the manuscripts. Two review authors independently assessed the risk of bias of relevant studies, with comments from a third author. Two authors extracted data onto a specially designed form.Main results We identified 31 studies, and 13 fulfilled the criteria for inclusion. We described trials that were not eligible for the review in the Discussion. The included studies involved a total of 85 participants, but the number in each individual trial was small; the largest treatment trial included 19 participants and the smallest study included only one participant. There was no benefit with: D-ribose,glucagon, verapamil, vitamin B6, branched chain amino acids, dantrolene sodium, and high-dose creatine. Minimal subjective benefit was found with low dose creatine and ramipril only for patients with a polymorphism known as the D/Dangiotens in converting enzyme(ACE) phenotype. A carbohydrate-rich diet resulted in better exercise performance compared with a protein-rich diet. Two studies of oral sucrose given at different times and in different amounts before exercise showed an improvement in exercise performance. Four studies reported adverse effects. Oral ribose caused diarrhoea and symptoms suggestive of hypoglycaemia including light-headedness and hunger. In one study, branched chain amino acids caused a deterioration of functional outcomes. Dantrolene was reported to cause a number of adverse effects including tiredness, somnolence, dizziness and muscle weakness. Low dose creatine (60 mg/kg/day) did not cause side-effects but high-dose creatine (150 mg/kg/day) worsened the symptoms of myalgia.Authors' conclusions Although there was low quality evidence of improvement in some parameters with creatine, oral sucrose, ramipril and a carbohydrate rich diet, none was sufficiently strong to indicate significant clinical benefit.
Topics: Creatine; Dietary Carbohydrates; Dietary Proteins; Dietary Supplements; Glycogen Storage Disease Type V; Humans; Physical Endurance; Ramipril; Randomized Controlled Trials as Topic; Sucrose
PubMed: 25391139
DOI: 10.1002/14651858.CD003458.pub5