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BMJ Open Jan 2020Essential tremor (ET), a tremor disorder, is one of the most common movement disorders. Only oral drugs (propranolol, primidone, topiramate, etc)are still the...
INTRODUCTION
Essential tremor (ET), a tremor disorder, is one of the most common movement disorders. Only oral drugs (propranolol, primidone, topiramate, etc)are still the first-line treatment recommended by the Food and Drug Administration. Propranolol is thought to potentially reduce upper limb action tremor. However, it has a poor effect on axial tremor symptoms, such as essential head tremor and voice tremor. Studies have shown that tremor severity develops over time, possibly producing other clinical tremors and neurological soft signs (such as memory loss, gait abnormalities, balance disorders, etc), which further increases the difficulty of treating tremors. However, some recent studies provide emerging evidence for oral propranolol on subgroups of ET, which is based on the anatomical distribution of ET (lower extremities, head, sound, tongue, etc). This systematic review aims to synthesise these new data to improve the efficacy of propranolol in ET subgroups.
METHODS AND ANALYSIS
We will search for randomised controlled trials from the PubMed, MEDLINE, EMBASE, Cochrane Library, UptoDate and PEDro databases from inception to June 2019. All data will be extracted independently by two reviewers and compared at the end of the review. The two reviewers will screen the study quality, and the Cochrane Collaboration's tool in Review Manager (RevMan) V.5.3.3 will be used to evaluate risk of bias. Our primary outcome will be the functional disability component related to tremors, as measured by the Fahn-Tolosa-Marin Tremor Rating Scale subscales B and C. Secondary outcomes will include severity of tremors and quality of life. Narrative and meta-analytical syntheses are planned.
ETHICS AND DISSEMINATION
Published aggregated data will be used in this review analysis and therefore no ethical approval is required. The results will be published in peer-reviewed journals, and proliferation activities will include diverse social stakeholders, non-academic groups and patients.
PROSPERO REGISTRATION NUMBER
CRD42018112580.
Topics: Humans; Administration, Oral; Adrenergic beta-Antagonists; Essential Tremor; Gait; Propranolol; Quality of Life; Treatment Outcome; Meta-Analysis as Topic; Systematic Reviews as Topic
PubMed: 31948986
DOI: 10.1136/bmjopen-2019-032096 -
Clinical Epidemiology 2021To determine the risk of hip fracture in persons with Alzheimer´s disease (AD) who initiated antiepileptic drugs (AEDs).
OBJECTIVE
To determine the risk of hip fracture in persons with Alzheimer´s disease (AD) who initiated antiepileptic drugs (AEDs).
METHODS
In the Medication use and AD (MEDALZ) cohort of 70,719 Finnish community dwellers with clinically verified incident AD diagnosis in 2005-2011, we identified all incident users of AEDs using national Prescription register. AEDs were classified as older (valproate, carbamazepine, clonazepam, phenytoin, levetiracetam, primidone) or newer (pregabalin, gabapentin, oxcarbazepine, lamotrigine, topiramate). We matched each user to 2 non-users. Incident hip fractures until 2015 were identified from the Care register for health care. We calculated inverse probability of treatment weighted hazard ratios (HR), with 95% confidence intervals, using Cox regression.
RESULTS
Altogether 5522 incident users were identified and matched to 11,044 non-users (in both groups, women: 65%; median age: 81 years). Altogether 53.3% of users initiated with newer AEDs (pregabalin 79.8%, gabapentin 10.2%) while 46.7% initiated with older AEDs (valproate 67.6%, carbamazepine 13.0%). Age- and sex-adjusted IR of hip fracture per 100 person-years was 1.8 (95% CI 1.6-1.9) in non-users and 2.0 (95% CI 1.8-2.2) in users. Increased risk of hip fracture was observed in users (HR 1.17, 95% CI 1.05-1.30) compared with non-users. The risk was higher for short duration of use (<14 weeks, HR 3.64, 95% CI 2.90-4.58) than for medium duration (14 to <64 weeks, HR 1.74, 95% CI 1.48-2.05) or ≥64 weeks' use (HR 1.23, 95% CI 1.08-1.40), compared to non-users with same follow-up time. Older AEDs had HR of 1.46 (1.03-2.08) compared with newer AEDs.
CONCLUSION
Our results imply that AED use is associated with an increased risk of hip fracture in people with AD. These findings prompt careful consideration before prescribing AEDs to persons with AD. Persons with AD treated with antiepileptics should be carefully monitored due to their increased risk of falling and fractures.
PubMed: 33911901
DOI: 10.2147/CLEP.S278306 -
Molecules (Basel, Switzerland) Nov 2023The objective of the present report was to develop and validate a simple, selective, and reproducible high-performance liquid chromatography method with UV detection...
The objective of the present report was to develop and validate a simple, selective, and reproducible high-performance liquid chromatography method with UV detection suitable for routine therapeutic drug monitoring of the most commonly used antiepileptic drugs and some of their metabolites. Simple precipitation of plasma proteins with acetonitrile was used for sample preparation. 10,11-dihydrocarbamazepine was used as an internal standard. Chromatographic separation of the analytes was achieved by gradient elution on a Phenyl-Hexyl column at 40 °C, using methanol and potassium phosphate buffer (25 mM; pH 5.1) as a mobile phase. The method was validated according to the FDA guidelines for bioanalytical method validation. It showed to be selective, accurate, precise, and linear over the concentration ranges of 1-50 mg/L for phenobarbital, phenytoin, levetiracetam, rufinamide, zonisamide, and lacosamide; 0.5-50 mg/L for lamotrigine, primidone, carbamazepine and 10-monohydroxycarbazepine; 0.2-10 mg/L for carbamazepine metabolites: 10,11-trans-dihydroxy-10,11-dihydrocarbamazepine and carbamazepine-10,11-epoxide; 0.1-10 mg/L for oxcarbazepine; 2-100 mg/L for felbamate and 3-150 mg/L for ethosuximide. The suitability of the validated method for routine therapeutic drug monitoring was confirmed by quantification of the analytes in plasma samples from patients with epilepsy on combination antiepileptic therapy.
Topics: Humans; Anticonvulsants; Chromatography, High Pressure Liquid; Drug Monitoring; Carbamazepine; Oxcarbazepine
PubMed: 38067559
DOI: 10.3390/molecules28237830 -
Molecules (Basel, Switzerland) May 2019In this work, primidone, a high persistent pharmacological drug typically found in urban wastewaters, was degraded by different ozone combined AOPs using TiO P25 and...
In this work, primidone, a high persistent pharmacological drug typically found in urban wastewaters, was degraded by different ozone combined AOPs using TiO P25 and commercial WO as photocatalyst. The comparison of processes, kinetics, nature of transformation products, and ecotoxicity of treated water samples, as well as the influence of the water matrix (ultrapure water or a secondary effluent), is presented and discussed. In presence of ozone, primidone is rapidly eliminated, with hydroxyl radicals being the main species involved. TiO was the most active catalyst regardless of the water matrix and the type of solar (global or visible) radiation applied. The synergy between ozone and photocatalysis (photocatalytic ozonation) for TOC removal was more evident at low O doses. In spite of having a lower band gap than TiO P25, WO did not bring any beneficial effects compared to TiO P25 regarding PRM and TOC removal. Based on the transformation products identified during ozonation and photocatalytic ozonation of primidone (hydroxyprimidone, phenyl-ethyl-malonamide, and 5-ethyldihydropirimidine-4,6(1H,5H)-dione), a degradation pathway is proposed. The application of the different processes resulted in an environmentally safe effluent for .
Topics: Animals; Catalysis; Daphnia; Hydroxyl Radical; Kinetics; Oxidation-Reduction; Oxides; Ozone; Photochemical Processes; Primidone; Sunlight; Titanium; Tungsten; Ultraviolet Rays; Water; Water Pollutants, Chemical; Water Purification
PubMed: 31058864
DOI: 10.3390/molecules24091728 -
Iranian Journal of Child Neurology 2017Anticonvulsant drugs can cause various forms of skin drug reactions, ranging from exanthema to severe blistering reactions. An association between HLA-B*1502 allele and...
OBJECTIVE
Anticonvulsant drugs can cause various forms of skin drug reactions, ranging from exanthema to severe blistering reactions. An association between HLA-B*1502 allele and severe skin reactions have been reported.
MATERIALS & METHODS
Fifteen patients with severe skin reactions following treatment with anticonvulsant drugs (Carbamazepine, lamotrigine, phenobarbital, primidone) and 15 controls (age-matched epileptic patients taking similar anticonvulsants without drug eruption) were included. They were referred to Mofid Children's Hospital in Tehran, Iran, between Jan 2012 to Jan 2014. Genomic DNA was extracted from peripheral blood of all patients and HLA- B*1502 genotype was detected by real-time PCR.
RESULTS
None of the patients was positive for HLA- B*1502, but two patients in control group had positive HLA- B*1502.
CONCLUSION
The HLA- B*1502 is not correlated with severe anticonvulsant drugs -induced skin reactions in Iranian children.
PubMed: 28698724
DOI: No ID Found -
BMC Psychiatry Jul 2015With aging of society the absolute number and the proportion of patients with cognitive deficits increase. Multiple disorders and diseases can foster cognitive...
BACKGROUND
With aging of society the absolute number and the proportion of patients with cognitive deficits increase. Multiple disorders and diseases can foster cognitive impairment, e.g., Alzheimer's disease (AD), depressive disorder, or polypharmacy.
CASE PRESENTATION
A 74 year old man presented to the Old Age Psychiatry Service with cognitive deficits while being treated for recurrent depressive episodes and essential tremor with Venlafaxine, Lithium, and Primidone. Neuropsychological testing revealed a medio-temporal pattern of deficits with pronounced impairment of episodic memory, particularly delayed recall. Likewise, cognitive flexibility, semantic fluency, and attention were impaired. Positron emission tomography (PET) with fluorodeoxyglucose was performed and revealed a pattern of glucose utilization deficit resembling AD. On cessation of treatment with Lithium and Primidone, cognitive performance improved, particularly episodic memory performance and cognitive flexibility. Likewise, glucose metabolism normalized. Despite normalization of both, clinical symptoms and glucose utilization, the patient remained worried about possible underlying Alzheimer's disease pathology. To rule this out, an amyloid-PET was performed. No cortical amyloid was observed.
CONCLUSION
Pharmacological treatment of older subjects may mimic glucose metabolism and clinical symptoms of Alzheimer's disease. In the present case both, imaging and clinical findings, reversed to normal on change of treatment. Amyloid PET is a helpful tool to additionally rule out underlying Alzheimer's disease in situations of clinical doubt even if clinical or other imaging findings are suggestive of Alzheimer's disease.
Topics: Aged; Alzheimer Disease; Anticonvulsants; Antidepressive Agents; Attention; Cognition Disorders; Depressive Disorder, Major; Diagnosis, Differential; Drug Therapy, Combination; Essential Tremor; Fluorodeoxyglucose F18; Glucose Metabolism Disorders; Humans; Lithium Compounds; Male; Memory Disorders; Memory, Episodic; Mental Recall; Neuropsychological Tests; Positron-Emission Tomography; Primidone; Radiopharmaceuticals; Recurrence; Venlafaxine Hydrochloride
PubMed: 26163145
DOI: 10.1186/s12888-015-0531-9 -
Journal of Clinical Movement Disorders 2015Essential tremor (ET) is a common condition associated with significant physical and psychosocial disability. "Classic" ET is a clinical syndrome of action tremor in the...
BACKGROUND
Essential tremor (ET) is a common condition associated with significant physical and psychosocial disability. "Classic" ET is a clinical syndrome of action tremor in the upper limbs and less commonly the head, jaw, voice, trunk, or lower limbs. Current diagnostic criteria for ET exclude isolated vocal tremor (IVT). Failure to recognize IVT as a form of ET may contribute to misdiagnosis and missed opportunities for treatment.
METHODS
We conducted a retrospective review of cases referred for voice disturbance. Patients with a primary diagnosis of vocal tremor were included while those with a diagnosis of spasmodic dysphonia where excluded.
RESULTS
19 cases of vocal tremor were identified, of which 17 patients (89%) were female. The average age of vocal symptom onset was 64 (SD 8.0) and patients had been symptomatic an average of 6 years (SD 4) at their initial visit. 8 patients had IVT while 11 also had evidence of subtle head or limb tremor. 8 patients (42%) had a family history of ET, with vocal tremor specifically identified in 5 of those cases (26%). 11 patients (58%) noted transient tremor improvement after alcohol consumption. Primidone and propranolol were the most common medications prescribed to these patients prior to consultation. 7 patients were given a trial of 1 gm of sodium oxybate in the office as part of a clinical trial, with at least mild improvement in vocal tremor noted by qualitative assessment.
CONCLUSIONS
ET may present as vocal tremor with little or no associated limb tremor. It may be a more common manifestation of ET in women. A family history of tremor and improvement in tremor after consuming alcohol can often be elicited on history. We propose that IVT may be part of the spectrum of ET.
PubMed: 26788340
DOI: 10.1186/s40734-015-0016-5 -
Journal of Clinical Movement Disorders 2014Task specific tremors in musicians have been mainly described as primary bowing tremor in string instrumentalists in relatively small sample sizes. Our aim was to...
BACKGROUND
Task specific tremors in musicians have been mainly described as primary bowing tremor in string instrumentalists in relatively small sample sizes. Our aim was to describe epidemiology, risk factors, phenomenology and treatment options of this disorder in 23 musicians of different instruments.
METHODS
We included 23 professional musicians (4 female, 19 male; mean age 51.5 ± 11.4 years) with a TSTM. During anamnesis, clinical examination, by mail or via telephone patients were asked for epidemiological, phenomenological information, risk factors and treatments. We then compared our findings to primary writing tremor, the most common task specific tremor.
RESULTS
Age at onset of the TST was 44.6 ± 13.6 years and tremor appeared 35.1 ± 13.5 years after beginning to play the instrument. The majority of patients were string instrumentalists, followed by woodwind instrumentalists. Other instrumentalists were a guitarist, pianist and percussionist respectively. In contrast to primary writing tremor, we also found proximal muscles of the upper extremity involved in tremor. A positive family history was found in Prior trauma was more common than in primary writing tremor. Treatment with a positive effect on tremor were in order of efficacy: Botulinumtoxin, Primidone, Propranolol, Trihexyphenidyl. No patient had undergone deep brain stimulation.
CONCLUSION
Task specific tremor in musicians is a heterogeneous disorder with a male gender predominance that shares many commonalities with PWT. The onset age as well as the time between starting to play the instrument and tremor onset has a wide range. Because previous trauma and overuse appear to be risk factors, preventive measures against playing related injuries are necessary. There appears to be a genetic predisposition for TST. No single beneficial medication exists and treatment of patients remains highly individual. It should be discussed, whether deep brain stimulation should be offered not only to patients that do not respond to any other medication but early in the course of the disease.
PubMed: 26788331
DOI: 10.1186/2054-7072-1-5 -
SAGE Open Medical Case Reports 2023Canavan disease is a rare fetal inherited leukodystrophy, caused by accumulation of N-acetyl-aspartate in the brain. Here, we report a child presented with frequent...
Canavan disease is a rare fetal inherited leukodystrophy, caused by accumulation of N-acetyl-aspartate in the brain. Here, we report a child presented with frequent intractable seizures and visual impairment. A 14-month-old female infant with a complaint of the absence of neck holding and generalized tonic-clonic seizures was referred to our hospital. Macrocephaly, setting sun eyes, tremor, and hypotonia were observed. Funduscopy showed optic atrophy. Our patient's flash visual evoked potential showed blindness. Her brain magnetic resonance imaging showed diffuse white matter in subcortical, basal ganglia, and dorsal pons. Electroencephalography showed diffuse slow and sharp waves. The genetic study detected a hemizygous mutation in the aspartoacylase gene. Our patient was diagnosed with Canavan disease and began anticonvulsant treatment. However, seizures were not under control. Then, her medications were discontinued, and clobazam and primidone were administered. In conclusion, starting clobazam and primidone may help prevent frequently intractable seizures in Canavan disease patients.
PubMed: 36968992
DOI: 10.1177/2050313X231160885 -
Journal of Pharmacy & Pharmaceutical... 2016The importance of HLA-B*15:02 genotyping to avoid carbamazepine induced SJS/TEN and molecular modeling to predict the role of HLA-B*15:0 and AEDs induced SJS/TEN are...
Coupling Genotyping and Computational Modeling in Prediction of Anti-epileptic Drugs that cause Stevens Johnson Syndrome and Toxic Epidermal Necrolysis for Carrier of HLA-B*15:02.
PURPOSE
The importance of HLA-B*15:02 genotyping to avoid carbamazepine induced SJS/TEN and molecular modeling to predict the role of HLA-B*15:0 and AEDs induced SJS/TEN are investigated.
METHODS
DNA was extracted from eighty-six patients. The patients were genotyped by AS-PCR. Computational modeling of the HLA-B*15:02 followed by docking studies were performed to screen 26 AEDs that may induce ADR among HLA-B*15:02 carriers.
RESULTS
Odd ratio for CBZ induced SJS/TEN and HLA-B*15:02 was 609.0 (95% CI: 23-15873; p=0.0002). Molecular modeling studies showed that acetazolamide, ethosuxiamide, lamotrigine, oxcarbazepine, phenobarbital, phenytoin, primidone and sodium-valproate may induce ADR in HLA-B*15:02 carriers alike CBZ. Conclusion. We confirmed HLA-B*15:02 as a predictor of SJS/TEN and recommend pre-screening. Computational prediction of DIHR is useful in personalized medicine.
Topics: Adolescent; Adult; Anticonvulsants; Carbamazepine; Female; Genotype; HLA-B Antigens; Heterozygote; Humans; Male; Middle Aged; Molecular Docking Simulation; Stevens-Johnson Syndrome; Young Adult
PubMed: 27096699
DOI: 10.18433/J38G7X