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Clinical Chemistry and Laboratory... Jun 2024
PubMed: 38905355
DOI: 10.1515/cclm-2024-0665 -
Cureus May 2024Phenytoin is a commonly prescribed antiepileptic medication for the prevention and treatment of tonic-clonic or partial seizures. Thrombocytopenia is a rare and serious...
Phenytoin is a commonly prescribed antiepileptic medication for the prevention and treatment of tonic-clonic or partial seizures. Thrombocytopenia is a rare and serious adverse effect of phenytoin. This case report presents the case of a patient with severe thrombocytopenia induced by phenytoin for the treatment of tonic-clonic seizures. A 63-year-old male received 300 mg/day of phenytoin for the treatment of tonic-clonic seizures. Seven days after receiving the first dose of phenytoin, he was diagnosed with severe thrombocytopenia (platelet count 44 x 10/L) without hemorrhage. Phenytoin was discontinued, and seizures were controlled with levetiracetam. Seven days after stopping phenytoin, his daily platelet count improved from 44 to 177 x 10/L. The Naranjo algorithm score of 7 was at a probable level for phenytoin-induced thrombocytopenia. Thrombocytopenia is a serious adverse drug reaction that can result in life-threatening bleeding. Phenytoin-induced thrombocytopenia commonly begins 1-90 days after administration, and the recovery time is 3-21 days. The potential mechanism of phenytoin-induced thrombocytopenia is drug-induced immune thrombocytopenia. Drugs that enhance the concentration of phenytoin epoxide may be a contributing factor in phenytoin-induced thrombocytopenia. Phenytoin-induced thrombocytopenia is a rare but serious hematological complication. It should be recognized early, particularly in patients with a high risk of hemorrhage or concurrently with medications that increase phenytoin epoxide. Regularly consecutive complete blood count tests may be essential in order to detect an early decrease in platelet count in these patients.
PubMed: 38899236
DOI: 10.7759/cureus.60669 -
Mikrochimica Acta Jun 2024Ultrathin molecularly imprinted polymer (MIP) films were deposited on the surfaces of ZnO nanorods (ZNRs) and nanosheets (ZNSs) by electropolymerization to afford...
Ultrathin molecularly imprinted polymer (MIP) films were deposited on the surfaces of ZnO nanorods (ZNRs) and nanosheets (ZNSs) by electropolymerization to afford extended-gate field-effect transistor sensors for detecting phenytoin (PHT) in plasma. Molecular imprinting efficiency was optimized by controlling the contents of functional monomers and the template in the precursor solution. PHT sensing was performed in plasma solutions with various concentrations by monitoring the drain current as a function of drain voltage under an applied gate voltage of 1.5 V. The reliability and reproducibility of the fabricated sensors were evaluated through a solution treatment process for complete PHT removal and PHT adsorption-removal cycling, while selectivity was examined by analyzing responses to chemicals with structures analogous to that of PHT. Compared with the ZNS/extracted-MIP sensor and sensors with non-imprinted polymer (NIP) films, the ZNR/extracted-MIP sensor showed superior responses to PHT-containing plasma due to selective PHT adsorption, achieving an imprinting factor of 4.23, detection limit of 12.9 ng/mL, quantitation limit of 53.0 ng/mL, and selectivity coefficients of 3-4 (against tramadol) and ~ 5 (against diphenhydramine). Therefore, we believe that the MIP-based ZNR sensing platform is promising for the practical detection of PHT and other drugs and evaluation of their proper dosages.
Topics: Anticonvulsants; Molecularly Imprinted Polymers; Transistors, Electronic; Limit of Detection; Zinc Oxide; Phenytoin; Humans; Molecular Imprinting; Nanotubes; Adsorption; Reproducibility of Results; Polymers
PubMed: 38879615
DOI: 10.1007/s00604-024-06487-x -
Journal of Pharmacy Practice Jun 2024Phenytoin (PHT) has been approved for the treatment of epilepsy. It belongs to the category of medications with a limited therapeutic window and requires therapeutic...
Phenytoin (PHT) has been approved for the treatment of epilepsy. It belongs to the category of medications with a limited therapeutic window and requires therapeutic drug monitoring (TDM). PTH has been observed to induce a variety of Adverse drug reactions (ADRs) including ataxia, dystonia, nystagmus, dyskinesia, etc. Phenytoin-induced ataxia is an uncommonly observed ADR of Phenytoin whose reports are extremely limited. Herein, we present a case report of a 16-year-old Asian patient with a past history of epilepsy that was admitted to a tertiary care hospital due to the development of ataxia, giddiness, and vomiting when taking Phenytoin in addition to Oxcarbazepine, Clobazam, and Levetiracetam to treat seizures. On admission, Magnetic resonance imaging (MRI) findings revealed bilateral variable cerebrospinal fluid (CSF) lesions in the parieto-occipital region of the periventricular area (periventricular leukomalacia). Additionally, serum Phenytoin levels were observed to be in the toxic range (40 μg/mL) due to which physicians confirmed the ADR to be due to Phenytoin toxicity. Thus, the Phenytoin drug was discontinued in the patient gradually and he was continued on clobazam, oxcarbazepine, and brivaracetam which led to reversal of the ADR in the patient. In this case, ataxia resulted from Phenytoin overdose, as confirmed by MRI and serum tests suggesting that TDM of Phenytoin is essential to prevent ADRs. Given the scarcity of ataxia cases caused by Phenytoin, awareness is lacking within the scientific community. Our aim is to provide insights to promote better monitoring and patient-centered treatment outcomes for epileptic patients.
PubMed: 38871356
DOI: 10.1177/08971900241262379 -
Experimental and Therapeutic Medicine Jul 2024Phenytoin (PHT)-induced gingival overgrowth is caused by the increased proliferation and reduced apoptosis of gingival fibroblasts in inflammatory gingiva. Licorice has...
Phenytoin (PHT)-induced gingival overgrowth is caused by the increased proliferation and reduced apoptosis of gingival fibroblasts in inflammatory gingiva. Licorice has long been used as a component of therapeutic preparations. It inhibits cell proliferation, induces cell apoptosis and has anti-inflammatory effects. 18-α-glycyrrhetinic acid (18α-GA), the active compound in licorice, promotes apoptosis in various types of cells. The present study determined whether 18α-GA affects apoptosis in gingival fibroblasts exposed to PHT. The present study aimed to establish a basis for the therapeutic application of 18α-GA to treat the gingival overgrowth induced by PHT. Human gingival fibroblasts from healthy donors were cultured to semi-confluence and then stimulated in serum-free DMEM containing PHT with or without 18α-GA for subsequent experiments. Apoptotic cells were detected by ELISA. Analysis of the distribution of cell cycle phases and the apoptotic cell population was performed by flow cytometry. The expression levels of mRNAs and proteins of apoptotic regulators were measured using reverse transcription-quantitative PCR and western blotting, respectively. Caspase (CASP) activities were assessed by an ELISA. Treatment with 18α-GA markedly increased the number of apoptotic cells, reduced BCL2 mRNA expression, increased CASP2 and receptor (TNFRSF)-interacting serine-threonine kinase 1 (RIPK1) domain containing adaptor with death domain, Fas (TNFRSF6)-associated via death domain, RIPK1, tumor necrosis factor receptor superfamily; member 1A, TNF receptor-associated factor 2, CASP2, CASP3 and CASP9 mRNA expression, and also upregulated the protein expression levels and activities of caspase-2, caspase-3 and caspase-9. These results demonstrated that 18α-GA induced apoptosis through the activation of the Fas and TNF pathways in the death receptor signaling pathway in gingival fibroblasts treated with PHT. 18α-GA exhibited therapeutic potential for the treatment of PHT-induced gingival overgrowth.
PubMed: 38868612
DOI: 10.3892/etm.2024.12586 -
Developmental Medicine and Child... Jun 2024Sturge-Weber syndrome (SWS) is a rare neurocutaneous syndrome, frequently associated with pharmaco-resistant, early-onset epilepsy. Optimal seizure control is paramount...
AIM
Sturge-Weber syndrome (SWS) is a rare neurocutaneous syndrome, frequently associated with pharmaco-resistant, early-onset epilepsy. Optimal seizure control is paramount to maximize neurodevelopment.
METHOD
A single-centre case series of 49 infants explored early SWS care. Ninety-two per cent of children developed seizures aged 0 to 3 years; 55% of cases were before diagnostic magnetic resonance imaging (MRI) or tertiary referral. Delay in SWS diagnosis affected 31% of infants because of a lack of gadolinium enhancement for initial MRI. First seizures were frequently prolonged, with phenytoin administration necessary in 46%. Presymptomatic antiseizure medication prophylaxis (n = 8/49) decreased seizure burden. No patients on antiseizure medication prophylaxis suffered status epilepticus for longer than 30 minutes, and half of them (n = 4) had not developed seizures at last follow-up (aged 2-10 years).
RESULTS
A parental survey enabled further service evaluation. Eighty-three per cent of parents considered local clinicians' understanding of SWS inadequate: 61% felt insufficiently informed about SWS and 81% received no epilepsy education before seizures.
INTERPRETATION
To overcome the identified shortfalls, guidelines towards improving and standardizing SWS management are proposed.
PubMed: 38867438
DOI: 10.1111/dmcn.15983 -
Cureus May 2024Sodium channel 8 alpha (SCN8A) mutations encompass a spectrum of epilepsy phenotypes with diverse clinical manifestations, posing diagnostic challenges. We present a...
Sodium channel 8 alpha (SCN8A) mutations encompass a spectrum of epilepsy phenotypes with diverse clinical manifestations, posing diagnostic challenges. We present a case of a nine-year-old male with SCN8A gene-associated developmental and epileptic encephalopathies (DEEs), characterized by generalized tonic-clonic seizures (GTCS) since infancy. Despite treatment with multiple antiepileptic drugs (AEDs), including phenytoin, valproate, levetiracetam, carbamazepine, and clobazam, seizure control remained elusive, prompting genetic testing. Whole exome sequencing confirmed a heterozygous mutation (p.Phe210Ser) in SCN8A exon 6, indicative of DEE-13. Functional studies revealed a gain-of-function mechanism in SCN8A variants, resulting in heightened ion channel activity and altered voltage dependence of activation. Despite treatment adjustments, the patient's seizures persisted until topiramate was introduced, offering partial relief. SCN8A, encoding Nav1.6 sodium channels, modulates neuronal excitability, with mutations leading to increased persistent currents and hyperexcitability. Early seizure onset and developmental delays are hallmarks of SCN8A-related DEE. This case highlights the significance of genetic testing in refractory epilepsy management, guiding personalized treatment strategies. Sodium channel blockers like phenytoin and carbamazepine are often first-line therapies, while topiramate presents as a potential adjunctive option in SCN8A-related DEE. Overall, this case underscores the diagnostic and therapeutic complexities of managing SCN8A-related epileptic encephalopathy, emphasizing the importance of long-term monitoring and personalized treatment approaches for optimizing outcomes in refractory epilepsy.
PubMed: 38846250
DOI: 10.7759/cureus.59775 -
Neurologia Jun 2024Status epilepticus is an important cause of pediatric neurological emergency. Immediate treatment is essential to prevent definitive neurological damage. Several...
INTRODUCTION
Status epilepticus is an important cause of pediatric neurological emergency. Immediate treatment is essential to prevent definitive neurological damage. Several antiepileptic drugs are available for the management of status epilepticus.
METHODS
Retrospective study of patients admitted at the emergency department of a tertiary hospital for 5 years (2014-2019). We analyzed the compliance to the treatment guidelines for pediatric status epilepticus.
RESULTS
One hundred and seventeen admissions were identified, 23.9% of these were febrile status epilepticus. Among the other cases, the most frequent cause was genetic (22.2%). The majority were convulsive status epilepticus (93.1%), 58.7% of which were generalized tonic-clonic seizures. Benzodiazepines were the most used first and second line drug (98.2% and 94.8%). The most frequent third drug used was diazepam (56.4%) followed by phenytoin (18.2%). An infra-therapeutic antiepileptic drug dose was given in 48.7% of cases. 49.6% presented with a prolonged status epilepticus and 6.8% needed intensive care. Incorrect sequence of drugs and infra-therapeutic doses were associated with prolonged status (p<0.001 and p<0.05) and an increased number of antiepileptic drugs used (p<0.001 and p<0.05).
CONCLUSIONS
Benzodiazepines were the most frequently first and second line drugs used for status epilepticus management. Surprisingly, the most frequently third line drugs used were also benzodiazepines. These findings were partially explained by the misuse of infra-therapeutic doses of these drugs. Noncompliance with the implemented guidelines was associated with unfavorable outcomes.
Topics: Humans; Status Epilepticus; Anticonvulsants; Retrospective Studies; Female; Male; Emergency Service, Hospital; Child; Child, Preschool; Infant; Benzodiazepines; Guideline Adherence; Adolescent; Diazepam
PubMed: 38830721
DOI: 10.1016/j.nrleng.2021.09.014 -
Continuum (Minneapolis, Minn.) Jun 2024Status epilepticus is a neurologic emergency that can be life- threatening. The key to effective management is recognition and prompt initiation of treatment. Management... (Review)
Review
OBJECTIVE
Status epilepticus is a neurologic emergency that can be life- threatening. The key to effective management is recognition and prompt initiation of treatment. Management of status epilepticus requires a patient-specific-approach framework, consisting of four axes: (1) semiology, (2) etiology, (3) EEG correlate, and (4) age. This article provides a comprehensive overview of status epilepticus, highlighting the current treatment approaches and strategies for management and control.
LATEST DEVELOPMENTS
Administering appropriate doses of antiseizure medication in a timely manner is vital for halting seizure activity. Benzodiazepines are the first-line treatment, as demonstrated by three randomized controlled trials in the hospital and prehospital settings. Benzodiazepines can be administered through IV, intramuscular, rectal, or intranasal routes. If seizures persist, second-line treatments such as phenytoin and fosphenytoin, valproate, or levetiracetam are warranted. The recently published Established Status Epilepticus Treatment Trial found that all three of these drugs are similarly effective in achieving seizure cessation in approximately half of patients. For cases of refractory and super-refractory status epilepticus, IV anesthetics, including ketamine and γ-aminobutyric acid-mediated (GABA-ergic) medications, are necessary. There is an increasing body of evidence supporting the use of ketamine, not only in the early phases of stage 3 status epilepticus but also as a second-line treatment option.
ESSENTIAL POINTS
As with other neurologic emergencies, "time is brain" when treating status epilepticus. Antiseizure medication should be initiated quickly to achieve seizure cessation. There is a need to explore newer generations of antiseizure medications and nonpharmacologic modalities to treat status epilepticus.
Topics: Humans; Status Epilepticus; Anticonvulsants; Male; Female; Disease Management; Electroencephalography
PubMed: 38830068
DOI: 10.1212/CON.0000000000001445