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Practical Neurology Oct 2021Trigeminal neuralgia (TN) is a highly disabling disorder characterised by very severe, brief and electric shock like recurrent episodes of facial pain. New diagnostic... (Review)
Review
Trigeminal neuralgia (TN) is a highly disabling disorder characterised by very severe, brief and electric shock like recurrent episodes of facial pain. New diagnostic criteria, which subclassify TN on the basis of presence of trigeminal neurovascular conflict or an underlying neurological disorder, should be used as they allow better characterisation of patients and help in decision-making regarding medical and surgical treatments. MR imaging, including high-resolution trigeminal sequences, should be performed as part of the diagnostic work-up. Carbamazepine and oxcarbazepine are drugs of first choice. Lamotrigine, gabapentin, pregabalin, botulinum toxin type A and baclofen can be used either alone or as add-on therapy. Surgery should be considered if the pain is poorly controlled or the medical treatments are poorly tolerated. Trigeminal microvascular decompression is the first-line surgery in patients with trigeminal neurovascular conflict while neuroablative surgical treatments can be offered if MR imaging does not show any neurovascular contact or where patients are considered too frail for microvascular decompression or do not wish to take the risk.
Topics: Anticonvulsants; Carbamazepine; Humans; Magnetic Resonance Imaging; Oxcarbazepine; Trigeminal Neuralgia
PubMed: 34108244
DOI: 10.1136/practneurol-2020-002782 -
Behavioural Neurology 2019Neuropathic pain is a chronic secondary pain condition, which is a consequence of peripheral or central nervous (somatosensory) system lesions or diseases. It is a... (Review)
Review
Neuropathic pain is a chronic secondary pain condition, which is a consequence of peripheral or central nervous (somatosensory) system lesions or diseases. It is a devastating condition, which affects around 7% of the general population. Numerous etiological factors contribute to the development of chronic neuropathic pain. It can originate from the peripheral part of the nervous system such as in the case of trigeminal or postherpetic neuralgia, peripheral nerve injury, painful polyneuropathies, or radiculopathies. Central chronic neuropathic pain can develop as a result of spinal cord or brain injury, stroke, or multiple sclerosis. As first-line pharmacological treatment options, tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors, and gabapentinoids are recommended. In trigeminal neuralgia, carbamazepine and oxcarbazepine are the first-choice drugs. In drug-refractory cases, interventional, physical, and psychological therapies are available. This review was structured based on a PubMed search of papers published in the field from 2010 until May 2019.
Topics: Antidepressive Agents, Tricyclic; Chronic Pain; Humans; Neuralgia; Prevalence; Quality of Life; Radiculopathy; Selective Serotonin Reuptake Inhibitors
PubMed: 31871494
DOI: 10.1155/2019/8685954 -
Molecular Pain 2020The trigeminal nerve (V) is the fifth and largest of all cranial nerves, and it is responsible for detecting sensory stimuli that arise from the craniofacial area. The... (Review)
Review
The trigeminal nerve (V) is the fifth and largest of all cranial nerves, and it is responsible for detecting sensory stimuli that arise from the craniofacial area. The nerve is divided into three branches: ophthalmic (V1), maxillary (V2), and mandibular (V3); their cell bodies are located in the trigeminal ganglia and they make connections with second-order neurons in the trigeminal brainstem sensory nuclear complex. Ascending projections via the trigeminothalamic tract transmit information to the thalamus and other brain regions responsible for interpreting sensory information. One of the most common forms of craniofacial pain is trigeminal neuralgia. Trigeminal neuralgia is characterized by sudden, brief, and excruciating facial pain attacks in one or more of the V branches, leading to a severe reduction in the quality of life of affected patients. Trigeminal neuralgia etiology can be classified into idiopathic, classic, and secondary. Classic trigeminal neuralgia is associated with neurovascular compression in the trigeminal root entry zone, which can lead to demyelination and a dysregulation of voltage-gated sodium channel expression in the membrane. These alterations may be responsible for pain attacks in trigeminal neuralgia patients. The antiepileptic drugs carbamazepine and oxcarbazepine are the first-line pharmacological treatment for trigeminal neuralgia. Their mechanism of action is a modulation of voltage-gated sodium channels, leading to a decrease in neuronal activity. Although carbamazepine and oxcarbazepine are the first-line treatment, other drugs may be useful for pain control in trigeminal neuralgia. Among them, the anticonvulsants gabapentin, pregabalin, lamotrigine and phenytoin, baclofen, and botulinum toxin type A can be coadministered with carbamazepine or oxcarbazepine for a synergistic approach. New pharmacological alternatives are being explored such as the active metabolite of oxcarbazepine, eslicarbazepine, and the new Nav1.7 blocker vixotrigine. The pharmacological profiles of these drugs are addressed in this review.
Topics: Animals; Anticonvulsants; Baclofen; Botulinum Toxins, Type A; Carbamazepine; Facial Pain; Gabapentin; Humans; Lamotrigine; Oxcarbazepine; Pain Management; Phenytoin; Pregabalin; Quality of Life; Trigeminal Neuralgia
PubMed: 31908187
DOI: 10.1177/1744806920901890 -
Deutsches Arzteblatt International Apr 2020Recent research findings have improved the understanding of the diagnosis, pathophysiology, genetics, etiology, and treatment of peripheral, central, and functional... (Review)
Review
BACKGROUND
Recent research findings have improved the understanding of the diagnosis, pathophysiology, genetics, etiology, and treatment of peripheral, central, and functional vestibular vertigo syndromes.
METHOD
A literature search, with special attention to the current classification, treatment trials, Cochrane analyses, and other meta-analyses.
RESULTS
There are internationally accepted diagnostic criteria for benign positional paroxysmal vertigo, Menière's disease, bilateral vestibulopathy, vestibular paroxysmia, and functional dizziness. Whether an acute vestibular syndrome is central or peripheral can usually be determined rapidly on the basis of the history and the clinical examination. "Cere - bellar vertigo" is a clinically important entity. For bilateral vestibulopathy, balance training is an effective treatment. For Menière's disease, preventive treatment with betahistine (48 mg and 144 mg per day) is not superior to placebo. For vestibular paroxysmia, oxcarbazepine has been shown to be effective. Treatments that are probably effective for functional dizziness include vestibular rehabilitation, cognitive behavioral therapy, and serotonin reuptake inhibitors.
CONCLUSION
The diagnostic assessment of vestibular syndromes is much easier for clinicians now that it has been internationally standardized. There is still a lack of randomized, controlled trials on the treatment of, for example, Menière's disease, vestibular migraine, and "cerebellar vertigo."
Topics: Humans; International Classification of Diseases; Meta-Analysis as Topic; Randomized Controlled Trials as Topic; Vestibular Diseases
PubMed: 32530417
DOI: 10.3238/arztebl.2020.0300 -
Therapeutic Advances in Neurological... 2022Women with epilepsy (WWE) wishing for a child represent a highly relevant subgroup of epilepsy patients. The treating epileptologist needs to delineate the epilepsy... (Review)
Review
Women with epilepsy (WWE) wishing for a child represent a highly relevant subgroup of epilepsy patients. The treating epileptologist needs to delineate the epilepsy syndrome and choose the appropriate anti-seizure medication (ASM) considering the main goal of seizure freedom, teratogenic risks, changes in drug metabolism during pregnancy and postpartum, demanding for up-titration during and down-titration after pregnancy. Folic acid or vitamin K supplements and breastfeeding are also discussed in this review. Lamotrigine and levetiracetam have the lowest teratogenic potential. Data on teratogenic risks are also favorable for oxcarbazepine, whereas topiramate tends to have an unfavorable profile. Valproate needs special emphasis. It is most effective in generalized seizures but should be avoided whenever possible due to its teratogenic effects and the negative impact on neuropsychological development of exposed children. Valproate still has its justification in patients not achieving seizure freedom with other ASMs or if a woman decides to or cannot become pregnant for any reason. When valproate is the most appropriate treatment option, the patient and caregiver must be fully informed of the risks associated with its use during pregnancies. Folate supplementation is recommended to reduce the risk of major congenital malformations. However, there is insufficient information to address the optimal dose and it is unclear whether higher doses offer greater protection. There is currently no general recommendation for a peripartum vitamin K prophylaxis. During pregnancy most ASMs (e.g. lamotrigine, oxcarbazepine, and levetiracetam) need to be increased to compensate for the decline in serum levels; exceptions are valproate and carbamazepine. Postpartum, baseline levels are reached relatively fast, and down-titration is performed empirically. Many ASMs in monotherapy are (moderately) safe for breastfeeding and women should be encouraged to do so. This review provides a practically oriented overview of the complex management of WWE before, during, and after pregnancy.
PubMed: 35706844
DOI: 10.1177/17562864221101687 -
Biomedicines Sep 2023This umbrella review aimed to determine the various drugs used to treat trigeminal neuralgia (TN) and to evaluate their efficacies as well as side effects by surveying... (Review)
Review
This umbrella review aimed to determine the various drugs used to treat trigeminal neuralgia (TN) and to evaluate their efficacies as well as side effects by surveying previously published reviews. An online search was conducted using PubMed, CRD, EBSCO, Web of Science, Scopus, and the Cochrane Library with no limits on publication date or patients' gender, age, and ethnicity. Reviews and meta-analyses of randomized controlled trials pertaining to drug therapy for TN, and other relevant review articles added from their reference lists, were evaluated. Rapid reviews, reviews published in languages other than English, and reviews of laboratory studies, case reports, and series were excluded. A total of 588 articles were initially collected; 127 full-text articles were evaluated after removing the duplicates and screening the titles and abstracts, and 11 articles were finally included in this study. Except for carbamazepine, most of the drugs had been inadequately studied. Carbamazepine and oxcarbazepine continue to be the first choice for medication for classical TN. Lamotrigine and baclofen can be regarded as second-line drugs to treat patients not responding to first-line medication or for patients having intolerable side effects from carbamazepine. Drug combinations using carbamazepine, baclofen, gabapentin, ropivacaine, tizanidine, and pimozide can yield satisfactory results and improve the tolerance to the treatment. Intravenous lidocaine can be used to treat acute exaggerations and botulinum toxin-A can be used in refractory cases. Proparacaine, dextromethorphan, and tocainide were reported to be inappropriate for treating TN. Anticonvulsants are successful in managing trigeminal neuralgia; nevertheless, there have been few studies with high levels of proof, making it challenging to compare or even combine their results in a statistically useful way. New research on other drugs, combination therapies, and newer formulations, such as vixotrigine, is awaited. There is conclusive evidence for the efficacy of pharmacological drugs in the treatment of TN.
PubMed: 37892981
DOI: 10.3390/biomedicines11102606 -
JAMA Neurology Jun 2023Prenatal antiseizure medication (ASM) exposure has been associated with adverse early neurodevelopment, but associations with a wider range of psychiatric end points...
IMPORTANCE
Prenatal antiseizure medication (ASM) exposure has been associated with adverse early neurodevelopment, but associations with a wider range of psychiatric end points have not been studied.
OBJECTIVE
To examine the association between prenatal exposure to ASM with a spectrum of psychiatric disorders in childhood and adolescence in children of mothers with epilepsy.
DESIGN, SETTING, AND PARTICIPANTS
This prospective, population-based register study assessed 4 546 605 singleton children born alive in Denmark, Finland, Iceland, Norway, and Sweden from January 1, 1996, to December 31, 2017. Of the 4 546 605 children, 54 953 with chromosomal disorders or uncertain birth characteristics were excluded, and 38 661 children of mothers with epilepsy were identified. Data analysis was performed from August 2021 to January 2023.
EXPOSURES
Prenatal exposure to ASM was defined as maternal prescription fills from 30 days before the first day of the last menstrual period until birth.
MAIN OUTCOMES AND MEASURES
The main outcome measure was diagnosis of psychiatric disorders (a combined end point and 13 individual disorders). Estimated adjusted hazard ratios (aHRs) using Cox proportional hazards regression and cumulative incidences with 95% CIs are reported.
RESULTS
Among the 38 661 children of mothers with epilepsy (16 458 [42.6%] exposed to ASM; 19 582 [51.3%] male; mean [SD] age at the end of study, 7.5 [4.6] years), prenatal valproate exposure was associated with an increased risk of the combined psychiatric end point (aHR, 1.80 [95% CI, 1.60-2.03]; cumulative risk at 18 years in ASM-exposed children, 42.1% [95% CI, 38.2%-45.8%]; cumulative risk at 18 years in unexposed children, 31.3% [95% CI, 28.9%-33.6%]), which was driven mainly by disorders within the neurodevelopmental spectrum. Prenatal exposure to lamotrigine, carbamazepine, and oxcarbazepine was not associated with an increased risk of psychiatric disorders, whereas associations were found for prenatal exposure to topiramate with attention-deficit/hyperactivity disorder (aHR, 2.38; 95% CI, 1.40-4.06) and exposure to levetiracetam with anxiety (aHR, 2.17; 95% CI, 1.26-3.72) and attention-deficit/hyperactivity disorder (aHR, 1.78; 95% CI, 1.03-3.07).
CONCLUSIONS AND RELEVANCE
Findings from this explorative study strengthen the evidence for the warning against the use of valproate in pregnancy and raise concern of risks of specific psychiatric disorders associated with topiramate and levetiracetam. This study provides reassuring evidence that lamotrigine, carbamazepine, and oxcarbazepine are not associated with long-term behavioral or developmental disorders but cannot rule out risks with higher doses.
Topics: Pregnancy; Child; Female; Male; Adolescent; Humans; Child, Preschool; Valproic Acid; Lamotrigine; Incidence; Levetiracetam; Topiramate; Prenatal Exposure Delayed Effects; Prospective Studies; Anticonvulsants; Epilepsy; Oxcarbazepine; Carbamazepine; Attention Deficit Disorder with Hyperactivity
PubMed: 37067807
DOI: 10.1001/jamaneurol.2023.0674 -
Seizure Dec 2020Epilepsy is one of the most common neurological disorders, affecting approximately 50 million people worldwide. Despite a dramatic increase in treatment options over the... (Review)
Review
Epilepsy is one of the most common neurological disorders, affecting approximately 50 million people worldwide. Despite a dramatic increase in treatment options over the past 30 years, it still ranks fourth in the world's disease burden. There are now close to 30 antiepileptic drugs (AEDs), with more than two thirds introduced to the market after carbamazepine (CBZ) and one third after its derivative, oxcarbazepine (OXC). Following the introduction of these newer AEDs, the role of CBZ and OXC in the therapeutic armamentarium for seizure control and effective epilepsy management needs to be reviewed. The main guidelines list both CBZ and OXC as first-line options or second-line alternatives for the treatment of focal-onset epilepsy and primary generalized tonic-clonic seizures. While evidence suggests that overall AEDs have similar efficacy, some newer AEDs may be better tolerated than CBZ. In line with this, there have been changes in treatment patterns, with many variations across different countries. However, CBZ remains among the two or three most prescribed drugs for focal epilepsy in many countries, and is widely used across Europe, Africa, South America, and Asia, where it represents a good compromise between cost, availability, and effectiveness. OXC is among the first-choice options for the initial treatment of focal-onset seizures in several countries, including the US and China, where the oral suspension is commonly prescribed. This review provides guidance on the optimal use of these two drugs in clinical practice, including in children, the elderly, and in pregnancy.
Topics: Anticonvulsants; Carbamazepine; Epilepsy; Epilepsy, Generalized; Humans; Oxcarbazepine; Topiramate
PubMed: 33334546
DOI: 10.1016/j.seizure.2020.10.018 -
Antiepileptic drug monotherapy for epilepsy: a network meta-analysis of individual participant data.The Cochrane Database of Systematic... Apr 2022This is an updated version of the original Cochrane Review published in 2017. Epilepsy is a common neurological condition with a worldwide prevalence of around 1%.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an updated version of the original Cochrane Review published in 2017. Epilepsy is a common neurological condition with a worldwide prevalence of around 1%. Approximately 60% to 70% of people with epilepsy will achieve a longer-term remission from seizures, and most achieve that remission shortly after starting antiepileptic drug treatment. Most people with epilepsy are treated with a single antiepileptic drug (monotherapy) and current guidelines from the National Institute for Health and Care Excellence (NICE) in the United Kingdom for adults and children recommend carbamazepine or lamotrigine as first-line treatment for focal onset seizures and sodium valproate for generalised onset seizures; however, a range of other antiepileptic drug (AED) treatments are available, and evidence is needed regarding their comparative effectiveness in order to inform treatment choices.
OBJECTIVES
To compare the time to treatment failure, remission and first seizure of 12 AEDs (carbamazepine, phenytoin, sodium valproate, phenobarbitone, oxcarbazepine, lamotrigine, gabapentin, topiramate, eventrate, zonisamide, eslicarbazepine acetate, lacosamide) currently used as monotherapy in children and adults with focal onset seizures (simple focal, complex focal or secondary generalised) or generalised tonic-clonic seizures with or without other generalised seizure types (absence, myoclonus).
SEARCH METHODS
For the latest update, we searched the following databases on 12 April 2021: the Cochrane Register of Studies (CRS Web), which includes PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Epilepsy Group Specialised Register and MEDLINE (Ovid, 1946 to April 09, 2021). We handsearched relevant journals and contacted pharmaceutical companies, original trial investigators and experts in the field.
SELECTION CRITERIA
We included randomised controlled trials of a monotherapy design in adults or children with focal onset seizures or generalised onset tonic-clonic seizures (with or without other generalised seizure types).
DATA COLLECTION AND ANALYSIS
This was an individual participant data (IPD) and network meta-analysis (NMA) review. Our primary outcome was 'time to treatment failure', and our secondary outcomes were 'time to achieve 12-month remission', 'time to achieve six-month remission', and 'time to first seizure post-randomisation'. We performed frequentist NMA to combine direct evidence with indirect evidence across the treatment network of 12 drugs. We investigated inconsistency between direct 'pairwise' estimates and NMA results via node splitting. Results are presented as hazard ratios (HRs) with 95% confidence intervals (CIs) and we assessed the certainty of the evidence using the CiNeMA approach, based on the GRADE framework. We have also provided a narrative summary of the most commonly reported adverse events.
MAIN RESULTS
IPD were provided for at least one outcome of this review for 14,789 out of a total of 22,049 eligible participants (67% of total data) from 39 out of the 89 eligible trials (43% of total trials). We could not include IPD from the remaining 50 trials in analysis for a variety of reasons, such as being unable to contact an author or sponsor to request data, data being lost or no longer available, cost and resources required to prepare data being prohibitive, or local authority or country-specific restrictions. No IPD were available from a single trial of eslicarbazepine acetate, so this AED could not be included in the NMA. Network meta-analysis showed high-certainty evidence that for our primary outcome, 'time to treatment failure', for individuals with focal seizures; lamotrigine performs better than most other treatments in terms of treatment failure for any reason and due to adverse events, including the other first-line treatment carbamazepine; HRs (95% CIs) for treatment failure for any reason for lamotrigine versus: eventrate 1.01 (0.88 to 1.20), zonisamide 1.18 (0.96 to 1.44), lacosamide 1.19 (0.90 to 1.58), carbamazepine 1.26 (1.10 to 1.44), oxcarbazepine 1.30 (1.02 to 1.66), sodium valproate 1.35 (1.09 to 1.69), phenytoin 1.44 (1.11 to 1.85), topiramate 1.50 (1.23 to 1.81), gabapentin 1.53 (1.26 to 1.85), phenobarbitone 1.97 (1.45 to 2.67). No significant difference between lamotrigine and eventrate was shown for any treatment failure outcome, and both AEDs seemed to perform better than all other AEDs. For people with generalised onset seizures, evidence was more limited and of moderate certainty; no other treatment performed better than first-line treatment sodium valproate, but there were no differences between sodium valproate, lamotrigine or eventrate in terms of treatment failure; HRs (95% CIs) for treatment failure for any reason for sodium valproate versus: lamotrigine 1.06 (0.81 to 1.37), eventrate 1.13 (0.89 to 1.42), gabapentin 1.13 (0.61 to 2.11), phenytoin 1.17 (0.80 to 1.73), oxcarbazepine 1.24 (0.72 to 2.14), topiramate 1.37 (1.06 to 1.77), carbamazepine 1.52 (1.18 to 1.96), phenobarbitone 2.13 (1.20 to 3.79), lacosamide 2.64 (1.14 to 6.09). Network meta-analysis also showed high-certainty evidence that for secondary remission outcomes, few notable differences were shown for either seizure type; for individuals with focal seizures, carbamazepine performed better than gabapentin (12-month remission) and sodium valproate (six-month remission). No differences between lamotrigine and any AED were shown for individuals with focal seizures, or between sodium valproate and other AEDs for individuals with generalised onset seizures. Network meta-analysis also showed high- to moderate-certainty evidence that, for 'time to first seizure,' in general, the earliest licensed treatments (phenytoin and phenobarbitone) performed better than the other treatments for individuals with focal seizures; phenobarbitone performed better than both first-line treatments carbamazepine and lamotrigine. There were no notable differences between the newer drugs (oxcarbazepine, topiramate, gabapentin, eventrate, zonisamide and lacosamide) for either seizure type. Generally, direct evidence (where available) and network meta-analysis estimates were numerically similar and consistent with confidence intervals of effect sizes overlapping. There was no important indication of inconsistency between direct and network meta-analysis results. The most commonly reported adverse events across all drugs were drowsiness/fatigue, headache or migraine, gastrointestinal disturbances, dizziness/faintness and rash or skin disorders; however, reporting of adverse events was highly variable across AEDs and across studies.
AUTHORS' CONCLUSIONS
High-certainty evidence demonstrates that for people with focal onset seizures, current first-line treatment options carbamazepine and lamotrigine, as well as newer drug eventrate, show the best profile in terms of treatment failure and seizure control as first-line treatments. For people with generalised tonic-clonic seizures (with or without other seizure types), current first-line treatment sodium valproate has the best profile compared to all other treatments, but lamotrigine and eventrate would be the most suitable alternative first-line treatments, particularly for those for whom sodium valproate may not be an appropriate treatment option. Further evidence from randomised controlled trials recruiting individuals with generalised tonic-clonic seizures (with or without other seizure types) is needed.
Topics: Adult; Anticonvulsants; Child; Epilepsies, Partial; Epilepsy; Humans; Network Meta-Analysis; Phenytoin
PubMed: 35363878
DOI: 10.1002/14651858.CD011412.pub4