Trigeminal neuralgia is characterized by severe, lightning-like attacks of pain, which are mandatory for the diagnosis. The pain typically occurs on one side and is often triggered by simply touching the face, chewing or talking. In acute exacerbations, this can also hinder food and fluid intake, resulting in a life-threatening clinical picture. A distinction is made between classical, secondary and idiopathic trigeminal neuralgia. For the diagnosis of trigeminal neuralgia, the medical history and imaging procedures are key for classification. The only active substances approved for the treatment of trigeminal neuralgia in Germany are carbamazepine and phenytoin, which is why off-label drugs often need to be used if there is no or insufficient effect or inacceptable side effects. Cooperation between research and clinical practice to improve the care of affected patients is therefore essential.
UNASSIGNED: Die Trigeminusneuralgie ist durch heftige, blitzartige Schmerzattacken gekennzeichnet, die für die Diagnose obligatorisch sind. Typischerweise treten die Schmerzen einseitig auf, oft werden sie durch einfache Berührungen des Gesichts, Kauen oder Sprechen ausgelöst. Dies kann bei akuten Exazerbationen auch die Nahrungs- und Flüssigkeitsaufnahme behindern, sodass es zu einem lebensbedrohlichen Krankheitsbild kommen kann. Es wird zwischen der klassischen, der sekundären und der idiopathischen Trigeminusneuralgie unterschieden. Für die Diagnose der Trigeminusneuralgie ist die Anamnese entscheidend, für die Einteilung sind es bildgebende Verfahren. Die einzigen in Deutschland zugelassenen Wirkstoffe zur Behandlung der Trigeminusneuralgie sind Carbamazepin und Phenytoin, weshalb häufig bei fehlendem oder unzureichendem Wirkeffekt bzw. bei inakzeptablen Nebenwirkungen Off-label-Medikamente eingesetzt werden müssen. Eine Zusammenarbeit von Forschung und klinischer Praxis zur Verbesserung der Versorgung betroffener Patienten ist daher essenziell.

By developing evidence-based pharmacogenetics guidelines to optimize pharmacotherapy, the Dutch Pharmacogenetics Working Group (DPWG) aims to advance the implementation of pharmacogenetics (PGx). This guideline outlines the gene-drug interaction of CYP2C9 and HLA-B with phenytoin, HLA-A and HLA-B with carbamazepine and HLA-B with oxcarbazepine and lamotrigine. A systematic review was performed and pharmacotherapeutic recommendations were developed. For CYP2C9 intermediate and poor metabolisers, the DPWG recommends lowering the daily dose of phenytoin and adjust based on effect and serum concentration after 7-10 days. For HLA-B*15:02 carriers, the risk of severe cutaneous adverse events associated with phenytoin, carbamazepine, oxcarbazepine, and lamotrigine is strongly increased. For carbamazepine, this risk is also increased in HLA-B*15:11 and HLA-A*31:01 carriers. For HLA-B*15:02, HLA-B*15:11 and HLA-A*31:01 positive patients, the DPWG recommends choosing an alternative anti-epileptic drug. If not possible, it is recommended to advise the patient to report any rash while using carbamazepine, lamotrigine, oxcarbazepine or phenytoin immediately. Carbamazepine should not be used in an HLA-B*15:02 positive patient. DPWG considers CYP2C9 genotyping before the start of phenytoin \"essential\" for toxicity prevention. For patients with an ancestry in which the abovementioned HLA-alleles are prevalent, the DPWG considers HLA-B*15:02 genotyping before the start of carbamazepine, phenytoin, oxcarbazepine, and lamotrigine \"beneficial\", as well as genotyping for HLA-B*15:11 and HLA-A*31:01 before initiating carbamazepine.

BACKGROUND: There is practice heterogeneity in the use, type, and duration of prophylactic antiseizure medications (ASMs) in patients with moderate-severe traumatic brain injury (TBI).
METHODS: We conducted a systematic review and meta-analysis of articles assessing ASM prophylaxis in adults with moderate-severe TBI (acute radiographic findings and requiring hospitalization). The population, intervention, comparator, and outcome (PICO) questions were as follows: (1) Should ASM versus no ASM be used in patients with moderate-severe TBI and no history of clinical or electrographic seizures? (2) If an ASM is used, should levetiracetam (LEV) or phenytoin/fosphenytoin (PHT/fPHT) be preferentially used? (3) If an ASM is used, should a long versus short (> 7 vs. ≤ 7 days) duration of prophylaxis be used? The main outcomes were early seizure, late seizure, adverse events, mortality, and functional outcomes. We used Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology to generate recommendations.
RESULTS: The initial literature search yielded 1998 articles, of which 33 formed the basis of the recommendations: PICO 1: We did not detect any significant positive or negative effect of ASM compared to no ASM on the outcomes of early seizure, late seizure, adverse events, or mortality. PICO 2: We did not detect any significant positive or negative effect of PHT/fPHT compared to LEV for early seizures or mortality, though point estimates suggest fewer late seizures and fewer adverse events with LEV. PICO 3: There were no significant differences in early or late seizures with longer versus shorter ASM use, though cognitive outcomes and adverse events appear worse with protracted use.
CONCLUSIONS: Based on GRADE criteria, we suggest that ASM or no ASM may be used in patients hospitalized with moderate-severe TBI (weak recommendation, low quality of evidence). If used, we suggest LEV over PHT/fPHT (weak recommendation, very low quality of evidence) for a short duration (≤ 7 days, weak recommendation, low quality of evidence).

Seizures are common in neonates, but there is substantial management variability. The Neonatal Task Force of the International League Against Epilepsy (ILAE) developed evidence-based recommendations about antiseizure medication (ASM) management in neonates in accordance with ILAE standards. Six priority questions were formulated, a systematic literature review and meta-analysis were performed, and results were reported following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 standards. Bias was evaluated using the Cochrane tool and risk of Bias in non-randomised studies - of interventions (ROBINS-I), and quality of evidence was evaluated using grading of recommendations, assessment, development and evaluation (GRADE). If insufficient evidence was available, then expert opinion was sought using Delphi consensus methodology. The strength of recommendations was defined according to the ILAE Clinical Practice Guidelines development tool. There were six main recommendations. First, phenobarbital should be the first-line ASM (evidence-based recommendation) regardless of etiology (expert agreement), unless channelopathy is likely the cause for seizures (e.g., due to family history), in which case phenytoin or carbamazepine should be used. Second, among neonates with seizures not responding to first-line ASM, phenytoin, levetiracetam, midazolam, or lidocaine may be used as a second-line ASM (expert agreement). In neonates with cardiac disorders, levetiracetam may be the preferred second-line ASM (expert agreement). Third, following cessation of acute provoked seizures without evidence for neonatal-onset epilepsy, ASMs should be discontinued before discharge home, regardless of magnetic resonance imaging or electroencephalographic findings (expert agreement). Fourth, therapeutic hypothermia may reduce seizure burden in neonates with hypoxic-ischemic encephalopathy (evidence-based recommendation). Fifth, treating neonatal seizures (including electrographic-only seizures) to achieve a lower seizure burden may be associated with improved outcome (expert agreement). Sixth, a trial of pyridoxine may be attempted in neonates presenting with clinical features of vitamin B6-dependent epilepsy and seizures unresponsive to second-line ASM (expert agreement). Additional considerations include a standardized pathway for the management of neonatal seizures in each neonatal unit and informing parents/guardians about the diagnosis of seizures and initial treatment options.

BACKGROUND: Concomitant administration of enteral nutrition (EN) and phenytoin decreases phenytoin absorption. Concerns over impaired nutrition, however, may prevent EN from being held surrounding phenytoin administration. This study aimed to evaluate whether EN holding guidelines impacted nutrition goal achievement in patients taking phenytoin.
METHODS: Adult patients administered enteral phenytoin for acute or chronic seizures while receiving EN during a neurocritical care admission 6 months before and after EN holding guideline implementation were eligible. Patients without phenytoin concentrations or a clinical registered dietitian assessment were excluded. The primary outcome was the percentage of nutrition daily goals attained before and after implementation. Secondary end points included the incidence of hypoglycemia, differences in measured phenytoin concentrations, and rates of therapeutic (10-20 mcg/ml) and high-therapeutic (15-20 mcg/ml) concentration attainment. Concentrations were adjusted for hypoalbuminemia using the Winter-Tozer equation.
RESULTS: Fifty-five patients representing 412 patient days and 1110 phenytoin administrations were included with 29 preimplementation and 26 postimplementation patients. Median percent attainment of daily EN goals was consistent preimplementation and postimplementation (86% vs 83%, P = 0.48). No significant change in rates of days with hypoglycemia was observed. Adjusted phenytoin concentrations were similar before and after implementation (14.1 vs 15.2 mcg/ml, P = 0.45), but the preimplementation cohort had a lower proportion of high-therapeutic concentrations (23% vs 36%, P = 0.018).
CONCLUSIONS: Holding EN for phenytoin did not impact attainment of daily nutrition goals and was not associated with increased rates of hypoglycemia. This is the first study to evaluate the effect of EN holding on nutrition goals in patients receiving phenytoin.

BACKGROUND: Neurocysticercosis (NCC) is a significant problem in India and other developing countries; however, several aspects of this disease have no clear, practical guidelines. There is a need for pragmatic guidelines, summarizing the available evidence, and filling in the gaps in evidence with expert advice to manage children with neurocysticercosis.
METHODS: An expert group (16 members) and a writing group (8 members) was constituted, consisting of members with varied expertise. It included pediatric neurologists (18), neurologist (1), Neuroradiologists (4), and a parasitologist (1). The writing group divided the six topics and reviewed the literature on the topics individually to determine the clinical questions for which no clear guidance was available from the literature. The experts were then contacted and opinions were obtained online. The Delphi consensus method was adopted to arrive at a general consensus regarding various questions, with both the experts and the writing group members contributing. The final guidelines were then drafted by the writing group.
CONCLUSIONS: Diagnosis of NCC should be based on clinical history and neuroimaging. Contrast-enhanced magnetic resonance imaging of the brain is the modality of choice. For single enhancing lesion, albendazole therapy for 10-14 days is recommended, and it should be combined with praziquantel for 10-14 days for more than one ring-enhancing lesions. For persistent lesion, the same dose and duration of albendazole or concurrent administration of albendazole and praziquantel should be given. Pulse intravenous steroids should be used to reduce the acute symptomatic edema in children with cysticercal encephalitis. Carbamazepine or oxcarbazepine are best suited for seizure prophylaxis for those who present with seizures; phenytoin and levetiracetam are the other alternatives. In the case of NCC presenting with symptoms other than seizures, there appears to be no role for routine anti-seizure medication prophylaxis. For a single ring-enhancing lesion, six months of anti-seizure medication is sufficient if the lesion resolves on follow-up. Those with persistent lesions, calcification, or multiple lesions, require a longer treatment duration of at least 24 months.

Phenytoin is an antiepileptic drug with a narrow therapeutic index and large interpatient pharmacokinetic variability, partly due to genetic variation in CYP2C9. Furthermore, the variant allele HLA-B*15:02 is associated with an increased risk of Stevens-Johnson syndrome and toxic epidermal necrolysis in response to phenytoin treatment. We summarize evidence from the published literature supporting these associations and provide therapeutic recommendations for the use of phenytoin based on CYP2C9 and/or HLA-B genotypes (updates on cpicpgx.org).

Trigeminal neuralgia (TN) is an extremely painful condition which can be difficult to diagnose and treat. In Europe, TN patients are managed by many different specialities. Therefore, there is a great need for comprehensive European guidelines for the management of TN. The European Academy of Neurology asked an expert panel to develop recommendations for a series of questions that are essential for daily clinical management of patients with TN.
A systematic review of the literature was performed and recommendations was developed based on GRADE, where feasible; if not, a good practice statement was given.
The use of the most recent classification system is recommended, which diagnoses TN as primary TN, either classical or idiopathic depending on the degree of neurovascular contact, or as secondary TN caused by pathology other than neurovascular contact. Magnetic resonance imaging (MRI), using a combination of three high-resolution sequences, should be performed as part of the work-up in TN patients, because no clinical characteristics can exclude secondary TN. If MRI is not possible, trigeminal reflexes can be used. Neurovascular contact plays an important role in primary TN, but demonstration of a neurovascular contact should not be used to confirm the diagnosis of TN. Rather, it may help to decide if and when a patient should be referred for microvascular decompression. In acute exacerbations of pain, intravenous infusion of fosphenytoin or lidocaine can be used. For long-term treatment, carbamazepine or oxcarbazepine are recommended as drugs of first choice. Lamotrigine, gabapentin, botulinum toxin type A, pregabalin, baclofen and phenytoin may be used either alone or as add-on therapy. It is recommended that patients should be offered surgery if pain is not sufficiently controlled medically or if medical treatment is poorly tolerated. Microvascular decompression is recommended as first-line surgery in patients with classical TN. No recommendation can be given for choice between any neuroablative treatments or between them and microvascular decompression in patients with idiopathic TN. Neuroablative treatments should be the preferred choice if MRI does not demonstrate any neurovascular contact. Treatment for patients with secondary TN should in general follow the same principles as for primary TN. In addition to medical and surgical management, it is recommended that patients are offered psychological and nursing support.
Compared with previous TN guidelines, there are important changes regarding diagnosis and imaging. These allow better characterization of patients and help in decision making regarding the planning of medical and surgical management. Recommendations on pharmacological and surgical management have been updated. There is a great need for future research on all aspects of TN, including pathophysiology and management.

Phenytoin is a widely used antiepileptic drug with a narrow therapeutic index and large interpatient variability, partly due to genetic variations in the gene encoding cytochrome P450 (CYP)2C9 (CYP2C9). Furthermore, the variant allele HLA-B*15:02, encoding human leukocyte antigen, is associated with an increased risk of Stevens-Johnson syndrome and toxic epidermal necrolysis in response to phenytoin treatment. We summarize evidence from the published literature supporting these associations and provide recommendations for the use of phenytoin based on CYP2C9 and/or HLA-B genotype (also available on PharmGKB: http://www.pharmgkb.org). The purpose of this guideline is to provide information for the interpretation of HLA-B and/or CYP2C9 genotype tests so that the results can guide dosing and/or use of phenytoin. Detailed guidelines for the use of phenytoin as well as analyses of cost-effectiveness are out of scope. Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines are periodically updated at http://www.pharmgkb.org.

BACKGROUND: Management of a patient with pressure ulcer sore(s) must associate local and general treatment.
OBJECTIVE: To determine which medical devices other than supports and which treatments may be used for pressure sore healing (granulation tissue and epithelization/epidermidalization) as of 2012.
METHODS: Systematic review of the literature querying the databases: PASCAL Biomed, PubMed, and Cochrane library from 2000 through 2010.
RESULTS: Data in the literature on granulation tissue and epithelisation/epidermidalization in pressure sore healing are poor. The level of evidence regarding the relative effectiveness of one modern dressing compared to another has remained low. However, the study data on the interest of hydrocolloid dressing compared with impregnated gases are more significant.
CONCLUSIONS: Studies with heterogeneous results and populations have shown low power. Meta-analyses are difficult due to the wide range of therapeutic aims. Further clinical studies with adequate methodology are needed prior to elaboration of more specific recommendations.
CONCLUSIONS: The use of hydrocolloid dressing may be recommended to improve granulation tissue development and epithelization/epidermidalization in pressure sore (Level B).