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Neurotherapeutics : the Journal of the... Oct 2020Essential tremor is one of the most common tremor syndromes. According to the recent tremor classification, tremor as a symptom is defined as an involuntary, rhythmic,... (Review)
Review
Essential tremor is one of the most common tremor syndromes. According to the recent tremor classification, tremor as a symptom is defined as an involuntary, rhythmic, oscillatory movement of a body part and is classified along two axes: axis 1-defining syndromes based on the clinical features such as historical features, tremor characteristics, associated signs, and laboratory tests; and axis 2-classifying the etiology (Bhatia et al., Mov Disord 33:75-87, 2018). The management of this condition has two major approaches. The first is to exclude treatable etiologies, as particularly during the onset of this condition the presentation of a variety of etiologies can be with monosymptomatic tremor. Once the few etiologies with causal treatments are excluded, all further treatment is symptomatic. Shared decision-making with enabling the patient to knowledgeably choose treatment options is needed to customize the management. Mild to moderate tremor severity can sometimes be controlled with occupational treatment, speech therapy of psychotherapy, or adaptation of coping strategy. First-line pharmacological treatments include symptomatic treatment with propranolol, primidone, and topiramate. Botulinum toxin is for selected cases. Invasive treatments for essential tremor should be considered for severe tremors. They are generally accepted as the most powerful interventions and provide not only improvement of tremor but also a significant improvement of life quality. The current standard is deep brain stimulation (DBS) of the thalamic and subthalamic region. Focused ultrasound thalamotomy is a new therapy attracting increasing interest. Radiofrequency lesioning is only rarely done if DBS or focused ultrasound is not possible. Radiosurgery is not well established. We present our treatment algorithm.
Topics: Behavior Therapy; Botulinum Toxins; Deep Brain Stimulation; Diagnosis, Differential; Disease Management; Essential Tremor; Humans; Occupational Therapy; Radiosurgery; Treatment Outcome
PubMed: 32915385
DOI: 10.1007/s13311-020-00899-2 -
Epilepsy Research Jul 2020Brivaracetam is an antiepileptic drug (AED) indicated for the treatment of focal seizures, with improved safety and tolerability vs first-generation AEDs. Brivaracetam... (Review)
Review
Brivaracetam is an antiepileptic drug (AED) indicated for the treatment of focal seizures, with improved safety and tolerability vs first-generation AEDs. Brivaracetam binds with high affinity to synaptic vesicle protein 2A in the brain, which confers its antiseizure activity. Brivaracetam is rapidly absorbed and extensively biotransformed, and exhibits linear and dose-proportional pharmacokinetics at therapeutic doses. Brivaracetam does not interact with most metabolizing enzymes and drug transporters, and therefore does not interfere with drugs that use these metabolic routes. The favorable pharmacokinetic profile of brivaracetam and lack of clinically relevant drug-drug interactions with commonly prescribed AEDs or oral contraceptives allows administration without dose adjustment, and avoids potential untoward events from decreased efficacy of an AED or oral contraceptive due to a drug-drug interaction. Few agents have been reported to affect the pharmacokinetics of brivaracetam. The strong enzyme-inducing AEDs carbamazepine, phenytoin and phenobarbital/primidone have been shown to moderately lower brivaracetam plasma concentrations, with no adjustment of brivaracetam dose needed. Dose adjustment should be considered when brivaracetam is coadministered with the more potent CYP inducer, rifampin. Additionally, caution should be used when adding or ending treatment with the strong enzyme inducer, St. John's wort. In summary, brivaracetam (50-200 mg/day) has a favorable pharmacokinetic profile and is associated with few clinically relevant drug-drug interactions.
Topics: Anticonvulsants; Brain; Carbamazepine; Drug Interactions; Humans; Pyrrolidinones; Seizures
PubMed: 32361205
DOI: 10.1016/j.eplepsyres.2020.106327 -
ELife Apr 2020Transient Receptor Potential Melastatin 3 (TRPM3) is a Ca permeable non-selective cation channel activated by heat and chemical agonists such as pregnenolone sulfate and...
Transient Receptor Potential Melastatin 3 (TRPM3) is a Ca permeable non-selective cation channel activated by heat and chemical agonists such as pregnenolone sulfate and CIM0216. TRPM3 mutations in humans were recently reported to be associated with intellectual disability and epilepsy; the functional effects of those mutations, however, were not reported. Here, we show that both disease-associated mutations in the human TRPM3 render the channel overactive, but likely via different mechanisms. The Val to Met substitution in the S4-S5 loop induced a larger increase in basal activity and agonist sensitivity at room temperature than the Pro to Gln substitution in the extracellular segment of S6. In contrast, heat activation was increased more by the S6 mutant than by the S4-S5 segment mutant. Both mutants were inhibited by the TRPM3 antagonist primidone, suggesting a potential therapeutic intervention to treat this disease.
Topics: Calcium; Cells, Cultured; Ganglia, Spinal; HEK293 Cells; Humans; Mutation; Pregnenolone; TRPM Cation Channels
PubMed: 32343227
DOI: 10.7554/eLife.55634 -
Therapie 2020Pitch perception modifications are among the little-known adverse effects observed with antiepileptics, mainly affecting patients treated with carbamazepine (CBZ). Here,...
Pitch perception modifications are among the little-known adverse effects observed with antiepileptics, mainly affecting patients treated with carbamazepine (CBZ). Here, we describe an original French case of pitch perception modification due to CBZ resulting in perfect pitch loss. We also reviewed the literature as well as French and world health organisation global pharmacovigilance database. The case report concerns a 22-year-old patient with perfect pitch with untreated left temporal partial epilepsy. Following a generalized seizure, the introduction of CBZ prolonged release (200mg twice a day) is decided. As soon as CBZ is introduced, the patient notices a change in pitch perception, about a semitone lower. This adverse effect persisted despite a gradual decrease in doses. The patient reported a total recovery of his perfect pitch when CBZ stopped completely 11 years later. In the French pharmacovigilance database, only one other case of pitch perception modification under CBZ was recorded (no cases were found with oxcarbazepine, lacosamide, sodium valproate, lamotrigine, levetiracetam, phenobarbital, phenytoin, primidone, ethosuximide, vigabatrine, felbamate, gabapentin, tiagabine and topiramate). In the literature, 27 cases of pitch perception modification have been published with CBZ, 1 case with oxcarbazepine and 1 case with lacosamide. Pitch perception modification is a very rare adverse effect of CBZ, oxcarbazepine and lacosamide, identified in the literature mainly in the Japanese population, in experienced musicians. A rapid onset after the introduction of treatment, a complete resolution of symptoms, in most cases upon discontinuation of treatment, is observed, with no sequelae reported. Due to the impact on quality of life, especially in patients whose profession is related to music, knowledge of this adverse event seems important to evoke this diagnosis.
Topics: Adult; Anticonvulsants; Epilepsy; Humans; Pharmacovigilance; Pitch Perception; Quality of Life; Young Adult
PubMed: 32204934
DOI: 10.1016/j.therap.2020.02.017 -
British Journal of Pharmacology Jun 2020The transient receptor potential (TRP) ion channel TRPM3 functions as a noxious heat sensor, plays a key role in acute pain sensation and inflammatory hyperalgesia in...
BACKGROUND AND PURPOSE
The transient receptor potential (TRP) ion channel TRPM3 functions as a noxious heat sensor, plays a key role in acute pain sensation and inflammatory hyperalgesia in rodents. Despite its potential as a novel analgesic drug target, little is known about the expression, function and modulation in the humans.
EXPERIMENTAL APPROACH
We studied TRPM3 in freshly isolated human dorsal root ganglion (hDRG) neurons and human stem cell-derived sensory (hSCDS) neurons. Expression was analysed at the mRNA level using RT-qPCR. Channel function was assessed using Fura-2-based calcium imaging and whole-cell patch-clamp recordings.
KEY RESULTS
TRPM3 was detected at the mRNA level in both hDRG and hSCDS neurons. The TRPM3 agonists pregnenolone sulphate (PS) and CIM0216 evoked robust intracellular Ca responses in 52% of hDRG and 58% of hSCDS neurons. Whole-cell patch-clamp recordings in hSCDS neurons revealed pregnenolone sulphate (PS)- and CIM0216-evoked currents exhibiting the characteristic current-voltage relation of TRPM3. PS-induced calcium responses in hSCDS neurons were reversed in a dose-dependent manner by the flavonoid isosakuranetin and by antiseizure drug primidone. Finally, the μ-opioid receptor agonist DAMGO and the GABA receptor agonist baclofen inhibited PS-evoked TRPM3 responses in a subset of hSCDS neurons.
CONCLUSION AND IMPLICATIONS
These results provide the first direct evidence of functional expression of the pain receptor TRPM3 in human sensory neurons, largely mirroring the channel's properties observed in mouse sensory neurons. hSCDS neurons represent a valuable and readily accessible in vitro model to study TRPM3 regulation and pharmacology in a relevant human cellular context.
Topics: Animals; Ganglia, Spinal; Humans; Hyperalgesia; Mice; Patch-Clamp Techniques; Sensory Receptor Cells; TRPM Cation Channels
PubMed: 31985045
DOI: 10.1111/bph.14994 -
Current Neuropharmacology 2020Essential Tremor (ET) is likely the most frequent movement disorder. In this review, we have summarized the current pharmacological options for the treatment of this... (Review)
Review
BACKGROUND
Essential Tremor (ET) is likely the most frequent movement disorder. In this review, we have summarized the current pharmacological options for the treatment of this disorder and discussed several future options derived from drugs tested in experimental models of ET or from neuropathological data.
METHODS
A literature search was performed on the pharmacology of essential tremors using PubMed Database from 1966 to July 31, 2019.
RESULTS
To date, the beta-blocker propranolol and the antiepileptic drug primidone are the drugs that have shown higher efficacy in the treatment of ET. Other drugs tested in ET patients have shown different degrees of efficacy or have not been useful.
CONCLUSION
Injections of botulinum toxin A could be useful in the treatment of some patients with ET refractory to pharmacotherapy. According to recent neurochemical data, drugs acting on the extrasynaptic GABAA receptors, the glutamatergic system or LINGO-1 could be interesting therapeutic options in the future.
Topics: Adrenergic beta-Antagonists; Animals; Anticonvulsants; Botulinum Toxins, Type A; Electrical Synapses; Essential Tremor; Humans; Neuropharmacology; Primidone; Propranolol
PubMed: 31976837
DOI: 10.2174/1570159X18666200124145743 -
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 -
Seizure Nov 2019Adverse cutaneous reactions caused by mostly aromatic antiepileptic drugs (AED) affect 50.000 people a year in the United Kingdom (UK; incidence 75.7/100.000). Optimal... (Review)
Review
Adverse cutaneous reactions caused by mostly aromatic antiepileptic drugs (AED) affect 50.000 people a year in the United Kingdom (UK; incidence 75.7/100.000). Optimal management of these cases is often difficult, as the patient may report symptoms to a general practitioner, attend Accident & Emergency or inform a specialist over the telephone or via email. When clinical assessment is limited it is thought safest to withdraw offending medication and inform the patient of a new drug allergy. This may unjustifiably restrict future treatment choices, and increase cost. Most frequent offenders are aromatic AEDs: carbamazepine, oxcarbazepine, eslicarbazepine, phenytoin, lamotrigine, phenobarbitone, primidone (recently licensed lacosamide associated with lower risk) and the sulpha-derivative zonisamide. Our study provides a summary of severe delayed allergic reactions and offers a pragmatic management pathway for patients suffering a suspected drug-induced rash. We include UK pretreatment screening guidelines, step by step clinical assessment of rash and associated symptoms aiding early identification of patients at risk of developing severe allergic reactions. At the same time our manuscript reviews published data informing best choice and titration of alternative medication when allergy confirmed. Finally we summarize current knowledge on genetic predisposition and other personalized risks of AED allergies identifying gaps in our current understanding.
Topics: Adult; Ambulatory Care; Anticonvulsants; Disease Management; Drug Hypersensitivity; Drug-Related Side Effects and Adverse Reactions; Epilepsy; Humans; Risk Factors; Stevens-Johnson Syndrome
PubMed: 31708349
DOI: 10.1016/j.seizure.2019.07.003 -
Revista de Neurologia Jul 2019In clinical practice, it is common to find cases of epileptic women being treated with antiepileptic drugs (AEDs) whom we have to advise on the compatibility of these... (Review)
Review
INTRODUCTION
In clinical practice, it is common to find cases of epileptic women being treated with antiepileptic drugs (AEDs) whom we have to advise on the compatibility of these AEDs with breastfeeding.
AIMS
In order to offer correct guidance, we must be well informed about the pharmacokinetic characteristics of the different AEDs, in addition to being aware of the clinical experience in this regard. This review stems from the paucity of information on this topic.
DEVELOPMENT
The World Health Organisation recommends that breastfeeding should be the norm for all women, even in epileptic mothers that are taking AEDs, who must always be given special attention in order to watch for the appearance of adverse effects in the infant, and always avoiding sudden weaning in order to avoid withdrawal symptoms.
CONCLUSIONS
Very few AEDs are incompatible with breastfeeding. The decision to breastfeed should take into account not only the AED, but also its number, dose, serum levels, transmission and elimination rates in the infant, and the conditions of the newborn infant. Ethosuximide and felbamate are probably high risk and incompatible with breastfeeding. Lamotrigine, phenobarbital, pregabalin, primidone, tiagabine, eslicarbazepine, brivaracetam, perampanel, zonisamide, lacosamide or the sporadic use of benzodiazepines in low doses are considered quite safe, with a low risk for breastfeeding. The other AEDs present a very low risk for breastfeeding.
Topics: Anticonvulsants; Breast Feeding; Epilepsy; Humans; Infant, Newborn
PubMed: 31287150
DOI: 10.33588/rn.6902.2019037