Drug-induced aseptic meningitis

Aseptic meningitis is a rare but well-recognized complication of drug therapy. The clinical presentation of drug-induced aseptic meningitis (DIAM) is distinct. Symptoms typically include fever, neck stiffness, headache, confusion, nausea and vomiting. The major categories of causative agents are non-steroidal anti-inflammatory drugs, antimicrobials and also intravenous immunoglobulins, monoclonal antibodies and vaccines. These drugs most commonly implicated as causes of aseptic meningitis act more likely through an immunological mechanisms. However, the exact pathogenetic mechanism of DIAM is still unknown. The diagnosis of drug-induced aseptic meningitis is difficult and infectious etiologies must be excluded. In some cases the diagnosis has been confirmed by rechallenging the patient with the suspected agent. In this case, informed written consent is necessary and rechallenge must be medically supervised both to document the response and to offer medical care and advice, if required. The outcome of DIAM is generally good, usually without long term sequelae.     

Drug-induced aseptic meningitis

Drug-induced aseptic meningitis (DIAM) is an important entity. This article reviews the literature on this rare idiosyncratic event which may occur after local or systemic drug administration. The data on this adverse reaction is predominantly collated from anecdotal case reports and case series.     

Levetiracetam induced acute reversible psychosis in a patient with uncontrolled seizures

Levetiracetam (LEV) is a relatively newer antiepileptic drug with novel mechanism of action. It was introduced to the market in the year 2000. Pre-marketing clinical trials of the drug reported good tolerability with a wide safety margin. On post-marketing updates, there are few reports of psychosis after treatment with the drug. Here, we report a case of 52-year-old epileptic man who developed acute, reversible psychosis within 3 days of initiation of treatment. The drug was prescribed at a dose of 500 mg per day. After 3 days of treatment, the patient developed visual hallucinations, mood swings, withdrawal and suspicious behavior. Delirium was ruled out as there was no fluctuation in his sensorium or focal neurological deficits. His lab investigations for electrolytes, renal function test, thyroid, liver function and other related tests levels were within normal limits. A diagnosis of LEV induced psychosis was reached based on clinical judgment and causality assessment.KEY WORDS: Adverse drug reaction, antiepileptic drugs, anti-seizure drug, levetiracetam, psychosis     

Drug-induced aseptic meningitis: diagnosis and management.

Drug-induced aseptic meningitis (DIAM) has been reported as an uncommon adverse reaction with numerous agents. It is a diagnosis of exclusion, and clinical signs and CSF findings vary greatly. The body of evidence regarding DIAM is largely in the form of anecdotal case reports and must be interpreted carefully bearing this in mind. The major categories of causative agents are nonsteroidal anti-inflammatory drugs, antimicrobials, intravenous immunoglobulin, intrathecal agents, vaccines and a number of other less frequently reported agents. There appears to be an association between DIAM and connective tissue disease, particularly systemic lupus erythematosus, and ibuprofen. There are 2 major proposed mechanisms for DIAM. The first involves direct irritation of the meninges by intrathecal administration of the drug, and the second involves immunological hypersensitivity to the drug, most likely type III and type IV hypersensitivity. Recognition and diagnosis of DIAM is important, as it is treatable by withdrawal of the drug and recurrence is prevented. The outcome of DIAM is generally good, usually without long term sequelae. This article describes the case reports of DIAM in the current literature and discusses the diagnosis and management of this rare complication.     

组织细胞性坏死性淋巴结炎合并无菌性脑膜炎 1例并文献回顾

目的探讨组织细胞性坏死性淋巴结炎(菊池病)合并无菌性脑膜炎病人的临床特点。方法回顾分析 2022年 6月 10日南京市第二医院收治的 1例以发热、头痛、呕吐为首发临床表现的菊池病病人的临床资料。结果该病人不明原因高热,头痛、呕吐,颈部淋巴结多发肿大,外院结核感染 T细胞斑点试验为阳性,怀疑为结核性脑膜炎转入该院,入院后血清学、脑脊液化验无结核感染依据,予经验性抗病毒、抗感染、降颅压治疗后未见好转,后经颈部淋巴结穿刺活检病理检查明确诊断为菊池病,予糖皮质激素口服后体温降至正常,头痛症状缓解,随访了解到病人颈部肿大淋巴结缩小,未有复发。结论菊池病合并无菌性脑膜炎临床上有些医生认知不足,容易误诊误治,对于有发热、颈部淋巴结肿大伴有无菌性脑膜炎表现的病人要注意考虑菊池病可能,尽早行淋巴结穿刺活检可及早明确诊断。     

Tuberculous meningitis presenting with unusually severe hyponatremia

We report a patient with tuberculous meningitis who presented with unusually severe hyponatremia, an electrolyte disorder that may cause symptoms similar to those of tuberculous meningitis. The hyponatremia was probably due to the syndrome of inappropriate antidiuretic hormone secretion, and resolved after instituting water restriction and antituberculous medication.     

Delayed Initiation of Remdesivir in a COVID-19-Positive Patient

We present a case of late initiation of remdesivir antiviral therapy in the successful treatment of a patient with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a mixed medical intensive care unit of a community teaching hospital. A previously healthy 40-year-old man was admitted to the hospital 3 days after the onset of coronavirus disease 2019 (COVID-19) symptoms including dry cough, fever, and shortness of breath progressing to intubation and increased mechanical ventilator support. A request for compassionate use remdesivir was submitted on the same hospital day as the positive COVID-19 polymerase chain reaction result. Supportive measures, in addition to a 5-day course of hydroxychloroquine, were maintained until remdesivir could be supplied on day 9 of hospitalization, 13 days after symptom onset. Sixty hours after initiating remdesivir, the patient was successfully extubated and able to transition to room air within 24 hours of extubation. Late initiation of remdesivir may be effective in treating SARS-CoV-2, unlike antivirals utilized for different disease states, such as oseltamivir, that are most effective when started as soon as possible following symptom onset. Urgent action is needed by regulatory agencies to work with drug manufacturers to expedite the study and approval of investigational agents targeting SARS-CoV-2 as well as to meet manufacturing demands.     

341 例癫痫患儿用药特点分析

目的：探讨癫痫患儿临床用药特点,为临床合理应用抗癫痫药物提供参考。方法：回顾性分析2018年2月至2018年8月西北妇女儿童医院和西安交通大学第二附附属医院收治的341例癫痫患儿临床资料,对其用药方案选择及发作控制率进行统计分析。结果：341例癫痫患儿中,男女比例1.04∶1,年龄9个月~19岁,其中1~3岁患儿占比最大,为32.55%。经抗癫痫药物治疗,341例患儿Ⅲ级以上总体发作控制率为84.45%。单药治疗、双药治疗和三种及以上联合治疗Ⅱ级以上控制率分别为94.45%、69.63%和45.56%。单药治疗中使用率前3位的药物分别为左乙拉西坦、苯巴比妥和卡马西平;多药治疗中使用率前3位的药物分别为左乙拉西坦、丙戊酸钠和托吡酯。单药治疗以左乙拉西坦为主,联合治疗主要以左乙拉西坦＋丙戊酸钠或托吡酯为主。结论：儿童癫痫发病以婴幼儿期最多,药物治疗总体控制率较高,新型抗癫痫药和传统抗癫痫药在治疗选择中使用率相当,新型抗癫痫药物左乙拉西坦在各发作类型及各种治疗方案中使用率最高。治疗药物选择主要为左乙拉西坦、苯巴比妥和卡马西平,抗癫痫药物联合治疗方案主要为丙戊酸钠+左乙拉西坦和丙戊酸钠+氯硝西泮+左乙拉西坦。     

Suspected allopurinol-induced aseptic meningitis.

Drug-induced aseptic meningitis is a syndrome with symptoms similar to those of infectious meningitis. A 60-year-old man with a history of recurrent renal stones was admitted to the hospital with fever, chills, and mental status changes after taking levofloxacin, allopurinol, and acetazolamide. No infectious source was identified. Once home, he resumed allopurinol, and within 2 hours, he experienced the same symptoms, requiring rehospitalization. He was diagnosed with suspected meningitis from an adverse drug reaction that we believe was due to allopurinol. It is important to remember, when all other causes are ruled out, that a patient's symptoms may be a drug-induced adverse effect. Drug-induced aseptic meningitis should be considered when patients with symptoms similar to those of infectious meningitis appear without infectious etiologies or cerebrospinal fluid pleocytosis, a suspected agent was recently started, and resolution of adverse effects occurs when the agent is withdrawn.     

左乙拉西坦相关血小板减少

左乙拉西坦(LEV)引起的血液系统不良反应包括白细胞减少、中性粒细胞减少、血小板减少及全血细胞减少,发生率为0.01%～0.13%。LEV相关血小板减少出现或加重的时间最短为用药后3 d,最长则可达到用药后60 d,同时还可伴有血红蛋白减少,或出现全血细胞减少。不良反应严重者血小板计数可降至1×109/L以下。除实验室检查发现的血小板计数减少外,临床还可出现黏膜出血、皮肤瘀斑、血尿等症状。LEV相关血小板减少的机制尚不清楚,骨髓抑制、免疫复合物形成、非免疫性直接破坏都有可能是LEV致血小板减少的机制。临床应用LEV后应密切观察相关症状和体征,定期检查血常规。一旦出现与血小板减少相关症状应及时停药,症状较轻者停药1周后可自行恢复,较重者可输注血小板,有严重出血症状者可短期给予糖皮质激素治疗。     

综合干预措施在清洁手术围手术期预防使用抗菌药管理中的效果

目的：评价综合干预措施在清洁手术围手术期预防应用抗菌药管理中的效果,提高使用抗菌药物的合理性。方法：随机抽取干预前2014年已出院清洁手术病历528例为对照组、干预后2017年已出院清洁手术614例为干预组,采用回顾性分析方法,从预防使用抗菌药物比例、预防用药时机合理性、抗菌药物品种选择、用药适应症合理性、疗程合理性、联合用药合理性、住院费用以及住院天数等方面进行统计,对比干预前、后围手术期预防应用抗菌药物上述各项的效果。结果：两组在预防使用抗菌药物比例、预防给药时机合格率、品种选择合格率、无适应症用药合格率、疗程合理性、联合用药、抗菌药物人均费用、住院药品人均费用、平均住院天数以及人均用药天数等,均有显著性差异（P＜0.05）。结论：我院清洁手术围手术期预防使用抗菌药物在综合干预措施后合理性得到大幅度提升,综合干预措施有力,效果明显。     

526例癫痫患儿用药情况调查

目的 了解我院癫痫患儿抗癫痫药物的使用情况,为临床用药及个体化给药提供参考。方法 对我院门诊526例癫痫患儿的抗癫痫药物的药品品种、血药浓度、症状控制情况进行统计、归纳和讨论。结果 我院抗癫痫药物以丙戊酸钠和卡马西平使用最多,两药对血药浓度控制较好,86%患儿的症状得到控制。结论 我院抗癫痫药物的使用基本合理,在用药过程中还应该加强药学服务和个体化给药。     

Serum concentrations of Levetiracetam in epileptic patients: the influence of dose and co-medication

Levetiracetam (LEV) is a new antiepileptic drug approved as add-on therapy. Previous studies indicated that LEV has no relevant interactions with other antiepileptic drugs. The aim of this study was to investigate the influence of LEV dose, age, and co-medication on the serum concentration of LEV. In total, 363 samples of 297 inpatients who fulfilled the inclusion criteria (e.g., trough concentration, body weight available) were investigated. A patient was considered twice only if his co-medication had been changed. The LEV serum concentration in relation to LEV dose/body weight [level-to-dose ratio, LDR, (microgram/mL)/(mg/kg)] was calculated and compared for the most frequent drug combinations. Analysis of covariance (using age as covariate) carried out on the log-transformed data showed that co-medication had a highly significant (P < 0.001) effect on LEV serum concentrations. The median LDR of LEV was 0.32 for LEV + phenytoin, 0.32 for LEV + carbamazepine, 0.34 LEV + oxcarbazepine, 0.45 for LEV + lamotrigine, 0.46 for LEV + phenobarital, 0.52 for LEV monotherapy, 0.53 for LEV + valproic acid, and 0.54 LEV + valproic acid + lamotrigine. In co-medication with phenytoin (P < 0.001), carbamazepine (P < 0.001), and oxcarbazepine (P < 0.004), the LDR of LEV was significantly lower than it was with LEV monotherapy, whereas the LDR of LEV of patients on co-medication with valproic acid or lamotrigine did not differ significantly from the LDR of LEV of patients on LEV monotherapy (P > 0.05). Regression analysis including all 363 samples confirmed that other drugs (e.g., phenytoin, carbamazepine) lower LEV concentrations. In addition to co-medication, age had a significant effect on clearance of LEV. Children had lower LEV concentrations than adults on the same LEV dose per body weight. In contrast to other studies, our data point out that other enzyme-inducing antiepileptic drugs (e.g., phenytoin, carbamazepine) can moderately decrease LEV serum concentrations (by 20-30%). However, our observations should be confirmed by prospective pharmacokinetic studies.     

Adverse effects of intravenous immunoglobulin therapy.

A growing body of literature documents that intravenous immunoglobulin prophylaxis and therapy is becoming applied to a steadily growing list of new indications. Some of these new indications have led to the use of intravenous immunoglobulin therapy in doctors offices, far from the hospital environment. Being stable products purified from blood or plasma donations, intravenous immunoglobulins must be considered as biological products in addition to their status as pharmaceutical products. This makes the study of adverse reactions reach beyond a mere drug safety surveillance programme into the realms of good manufacturing procedures guaranteeing not only intravenous tolerance but also sterility with regard to transfusion transmitted agents. The initially perceived adverse effects, stemming from complement activating aggregated immunoglobulin G, had the effect of slowing down widespread introduction of intravenous immunoglobulin therapy in the late 1970s. These adverse effects have now been eliminated with amendment of the appropriate manufacturing steps. However, new adverse effects, such as hyperviscosity, aseptic meningitis or renal insufficiency, have been observed which can be assigned to certain comnpounds of intravenous immunoglobulin, to administration regimens or to special patient characteristics. Adverse effects can be divided into 3 types: immediate adverse effects (those that occur during the infusion, e.g. anaphylactoid reactions); delayed adverse effects (those that occur hours to days after initiation of the infusion, e.g. renal, pulmonary, dermatological adverse effects, hyperviscosity, aseptic meningitis, arthritis, cerebral infarction, haemolysis and leucopenia) and; late adverse effects (e.g. transmission of infectious agents). We conclude from our analysis, that in general, intravenous immunoglobulin may be considered a well tolerated medical agent provided the indication for use is chosen carefully and use is monitored by a physician familiar with contraindications, risks, adverse effects and their appropriate management.     

Pregabalin-associated stuttering and frequent blepharospasm: case report and review.

Herpes zoster is an acute, painful, herpes skin disease caused by varicella-zoster virus, which may cause viral meningitis. Pregabalin has been shown to be efficacious in the treatment of pain in patients with herpes zoster. However, it has the side effects of neurotoxicity. We describe a 68-year-old female patient with herpes zoster, and she was treated with pregabalin. The patient presented with stuttering and frequent blepharospasm after 3 days of pregabalin treatment. Pregabalin was discontinued, the symptoms of stuttering and frequent blepharospasm completely resolved without any special treatment after one week. In this case, the etiology of stuttering and frequent blepharospasm may be related to pregabalin. Clinicians should be alert to the rare symptoms associated with the use of pregabalin.Graphical abstractOpen in a separate window.     

左乙拉西坦对癫痫患儿骨代谢影响的临床观察

目的:探讨抗癫痫药左乙拉西坦(LEV)对癫痫患儿骨代谢的影响。方法:选择2008年1月—2010年2月期间在唐山市妇幼保健院首发初诊的原发性癫痫患儿30例,予口服LEV治疗。于治疗前和治疗后6个月、12个月分别测定骨密度(BMD)、骨碱性磷酸酶(BAP)、血钙(Ca2+)、血磷(P)、血中碱性磷酸酶(ALP)。对照组为30例未治疗的原发性癫痫患儿,同期检测上述指标。对上述骨代谢指标进行评价。结果:左乙拉西坦治疗前后骨代谢指标差异无显著性(P>0.05)。左乙拉西坦治疗前、治疗后6个月、12个月BMD、BAP、Ca、P、ALP与对照组比较差异无显著性(P>0.05)。结论:短期服用左乙拉西坦(LEV)对癫痫患儿骨代谢无明显影响。     

Enteroviral meningitis. Cost of illness and considerations for the economic evaluation of potential therapies

With limited financial resources available, it is now becoming more acceptable to evaluate medical innovations in terms of incremental economic value. The purpose of this paper is to provide an overview of enteroviral meningitis and to summarise the economic literature to identify relevant costs and outcomes. Enteroviral meningitis is the most common cause of aseptic meningitis, and occurs in 4.5 to 30 per 100,000 population annually with a duration of illness lasting between 1 and 2 weeks after onset of initial symptoms. The major resource categories that contribute to the overall direct costs of management of enteroviral meningitis include physician visits, hospital admissions, emergency room visits, medications, procedures such as lumbar puncture and computed tomography scans, re-hospitalizations and follow-up physician visits. Indirect costs are incurred in terms of school or work days missed or restrictions in daily activities. The total direct costs of an episode of enteroviral meningitis range from $US450 for outpatients to $US5093 for inpatient management (1996 values). The total indirect costs of an episode of enteroviral meningitis are estimated to be equivalent to 5 to 7 activity-restricted days. Interventions that improve early diagnosis or decrease the duration and need for hospitalisation will significantly affect the cost of managing enteroviral meningitis. Additional prospective studies are needed to study the impact of interventions on the burden of enteroviral meningitis.     

Early‐Onset 5‐Fluorouracil Toxicity in a Patient Negative for Dihydropyrimidine Dehydrogenase Mutations: The Clinical Course of Reversal with Uridine Triacetate

An antimetabolite pyridine analog, 5‐fluorouracil (5‐FU), is used to treat solid tumors. Early toxicities may occur at standard doses of 5‐FU due to dihydropyrimidine dehydrogenase (DPD) deficiency. Uridine triacetate, approved by the Food and Drug Administration in 2015, is an oral prodrug of uridine, a pharmacologic antidote for 5‐FU toxicity. To our knowledge, this is the first case report that documents the clinical course of a patient treated with uridine triacetate to reverse early‐onset 5‐FU toxicity negative for DPD mutations. We describe the case of a 73‐year‐old man with anal cancer treated with standard‐of‐care chemotherapy and radiation. Two days after completion of his initial 5‐FU infusion, the patient developed severe mucositis and extreme fatigue, followed by a rapid decline in his blood cell counts and fevers. The patient was initiated on uridine triacetate 86 hours after completion of his 5‐FU infusion. Over a 10‐day hospital length of stay, the patient's absolute neutrophil count recovered to within normal limits, and his mucositis significantly improved. At follow‐up visits, the patient denied any residual symptoms of 5‐FU toxicity. We describe the patient's clinical course from hospital presentation to 31 days after initiation of uridine triacetate.     

Efficacy and safety of levetiracetam in pediatric epilepsy

ObjectiveTo evaluate the efficacy and tolerability of Levetiracetam (LEV) as an adjunctive therapy in pediatric patients with different generalized epilepsies.DesignChart review of 22 consecutive children age 4–19 years who were treated with LEV for at least 1 year was observed retrospectively. The mean dose rang of LEV was from 250 to 2000 mg. Data were collected on epilepsy type, seizure frequency, concomitant antiepileptic drug and adverse effect.ResultsOf the 22 patient reviewed, 13 (59%) were boys and 9 (41%) were girls. Predominant seizure types were generalized tonic–clonic seizures 13 (59%) and tonic seizure 6 (27%). Other seizure types included myoclonic seizures 2 (9%) and focal seizure 3 (5%). The results showed 10 (45%) had become free of seizure for almost 7 months to 1 year. Eight of these 10 patients (80%) had normalized EEG. Seizure frequency was reduced in 9 (41%) patients and 3 (14%) patients still had seizure. No side effects were reported related to LEV treated patients except for 1 patient.ConclusionOur results confirm that LEV may be an effective adjunctive therapy in treatment of childhood epilepsy, especially tonic–clonic seizure, with possible no evident side effect.     

Bacterial meningitis associated with infliximab

We report an episode of bacterial meningitis in a 45 year-old woman, who was treated with infliximab for Wegener’s granulomatosis. This patient presented with the classic clinical presentation of acute meningitis: the triad of fever, neck stiffness, and an altered mental state that appeared 6 months after the infliximab initiation. A computed tomographic (CT) scan of the head showed cerebral edema and Streptococcus peumoniae was isolated from blood and CSF cultures. Prompt diagnosis and early treatment improved the outcome of this patient.