Discontinuation Of Levetiracetam Research Articles

Discontinuation of Levetiracetam and Valproic Acid Due to Adverse Effects in Early Post-traumatic Seizure Prophylaxis.

Levetiracetam (LEV) and valproic acid (VPA) are two anti-epileptic drugs (AEDs) routinely used for post-traumatic seizure (PTS) prophylaxis at our institution. In our practice, VPA is used for its beneficial effects on behavioral agitation and headaches, but it is also associated with abnormal liver function tests (LFTs). Both medications may be associated with thrombocytopenia. There is less literature comparing the adverse effect profiles and discontinuation rates of LEV and VPA in the context of PTS prophylaxis. We conducted a quality improvement (QI) analysis to determine the safety of LEV and VPA for traumatic brain injury (TBI) patients at our institution. In particular, our QI analysis involved calculating the rates of discontinuation or change of drug regimen due to the adverse effects. Our QI analysis focused on patients treated for TBI at our institution during a six-year period. We recorded the AED usedand if the AED was discontinued or switched due to thrombocytopenia, behavioral agitation, headaches, or elevated LFTs (including elevated aspartate aminotransferase or alanine aminotransferase values). We also recorded the incidence of early PTS, defined as seizures within seven days of the TBI. Our QI analysis included patients with a mean age of approximately 49 years with nearly 75% males. The mean Glasgow Coma Scale (GCS) score was 12.88, with 73.11% of patients having a mild GCS. The three leading injury mechanisms were fall, assault, and motor vehicle collision. The three leading types of TBI were traumatic subarachnoid hemorrhage, subdural hematoma, and cerebral contusion. Among patients with no prior history of seizures, we found an early PTS incidence of 7.28%. For patients administered LEV and VPA, 0.11% (1/898) and 3.85% (4/104)had the medication discontinued or changed because of thrombocytopenia (p < 0.001), respectively. For patients on LEV, 4.01% (36/898) and 1.78% (16/898) had the medication discontinued or changed because of behavioral agitation and headaches, respectively. For patients on VPA, 2.88% (3/104) had the medication discontinued or changed because of hepatotoxicity. In total, 5.90% versus 6.73% (p > 0.5) of patients on LEV and VPA, respectively, had their medication regimens changed due to the adverse effects. The incidence of early PTS in our patients is within the range of what has been reported in the literature. The rate of discontinuation of LEV and VPA on account of adverse events is low in the context of PTS prophylaxis. Both medications had similar overall rates of discontinuation. VPA was discontinued more frequently than LEV due to thrombocytopenia, but discontinuation was not common in either case. LEV is associated with behavioral agitation and headaches, which makes VPA a desirable alternative for patients suffering from these symptoms.

Management of epilepsy in Alzheimer’s disease in Down syndrome

AbstractIntroductionDown syndrome (DS) is a genetically determined form of Alzheimer’s disease (AD) and a specific form of epilepsy is strongly associated with AD in DS (DSAD), late onset myoclonic epilepsy (LOMEDs), but, there are no clinical trials evaluating the efficacy and tolerability of antiseizure medications in this epilepsyAimsTo describe our experience in the treatment of LOMEDs.Material and MethodsWe recruited patients with symptomatic AD (prodromal –pAD‐ or AD dementia –dAD‐ stages) in the context of a health plan for adult population with DS between January 2013 and November 2021. This health plan included semiannual follow‐ups (or as clinically needed) and an anamnesis and structured questionnaire including the personal history of epilepsy (duration of epilepsy, semiology, frequency, efficacy and tolerability of ASM).ResultsThe study included 72 patients with pAD (48.6% females) and 257 with dAD (50.6% females). Bilateral tonic‐clonic seizures (BTCS) were the most frequent type (85.7% in pAD and 70.7% in dDS) and frequentlly coexisted with myoclonic seizures (16.7% and 57.6% in pDS and dAD respectively). The most frequent treatment after the first seizure was levetiracetam (LEV) (61.5%) followed by valproate (VPA) (19.6%). During follow‐up, 75.8% were on monotherapy with LEV (56.3%), VPA (25.5%) or brivaracetam (BRV) (8.2%). LEV was discontinued due to irritability in 21.9% of patients (interestingly 48% tolerated BRV after LEV discontinuation).VPA was abandoned in 14% due to motor worsening. Seizure control at one year was achieved in 65.9%, when considering BTCS, but only 30.2% were free of of myoclonic seizures.DiscussionLOMEDs is a very common comorbidity in DSAD that responds partially to treatment. BTCS seem to have a better response to treatment compared to myoclonic seizures.

Acute rhabdomyolysis due to levetiracetam in a two-year-old girl

Levetiracetam is one of the safest drugs which is used for the treatment of focal and generalized seizures during childhood. Until now, few patients have been reported with the diagnosis of acute rhabdomyolysis due to levetiracetam and our case is the youngest patient in the literature. Two-year old girl followed with atypical Rett syndrome (CDKL 5 deficiency) was admitted to our hospital with pneumonia and respiratory insufficiency. She was receiving intravenous antibiotics and levetiracetam therapy. During follow-up, the increase of creatine kinase levels continued, intravenous hydration and alkalinization was added on therapy. As we could not find any etiology explaining the raising creatine kinase levels in our patient, levetiracetam was thought to be the cause of rhabdomyolysis and withdrawn. After discontinuation of levetiracetam, creatine kinase levels began to decline within 24 h and returned to normal levels in one week. Levetiracetam-induced rhabdomyolysis is quite rare but is a life-threatening condition and should be kept in mind especially during childhood. The creatine kinase levels and renal function tests of all patients should be followed in the first week of levetiracetam therapy. Early diagnosis and supportive therapy is very important in order to prevent acute kidney injury. CDKL 5 deficiency can be a protective factor which might prevent acute kidney injury in our patient but more research is needed about this topic.

Brivaracetam for the treatment of refractory epilepsy in patients with prior exposure to levetiracetam: A retrospective outcome analysis

PurposeTo determine whether brivaracetam (BRV) provides an evident improvement in treatment efficacy and a reduction in treatment-emergent adverse events (TEAEs) in patients with refractory epilepsy, who previously failed treatment with levetiracetam (LEV). DesignRetrospective analysis of data extracted from electronic patient files at Epilepsy Centre Kempenhaeghe (Heeze, the Netherlands) from the year 2000 until October 2020. MethodsThe inclusion criteria were met by 407 patients >18 years of age. During data collection, 26 patients were excluded due to too little follow-up information on the use of either LEV or BRV, and two more due to poor medication compliance, leaving a total of 379 patients for further analyses. All had used LEV before they started treatment with BRV. For every patient, data were collected including demographic information, efficacy (positive responder or non-responder) of LEV and BRV, and TEAEs occurring during LEV and BRV treatment. ResultsA total of 121 (29.8%) patients had discontinued BRV treatment before the end of data collection. At time of data collection the mean time since first seizure was 25.4 years. Of the 379 patients, 82.8% were diagnosed with focal epilepsy and 9.8% with generalized epilepsy. The median duration of treatment was 39 months for LEV and 20 months for BRV, the mean maximum dose was 1749.9 mg/day for LEV and 144.2 mg/day for BRV, and the mean number of concomitant AEDs was 1.4 at the start of LEV treatment and 2.0 at the start of BRV treatment. LEV was switched directly to BRV in 208 (54.9%) patients; 171 (45.1%) patients had an interval between discontinuation of LEV and the start of BRV. The mean duration of interval was 77.7 months. Of the patients who discontinued BRV, 30 (24.8%) switched back to LEV. Discontinuation of initial LEV treatment was due to TEAEs in 63.6% of patients, including 55.1% because of behavioural TEAEs. Discontinuation of BRV was due to inadequate efficacy in 24.0% of patients, to TEAEs in 47.1% and to both inadequate efficacy and TEAEs in 22.3%. Concerning efficacy, the analysis showed no significant difference between the positive responder rate of LEV and BRV (72.0% vs 69.1%, p>0.05). Of the patients who were positive responders to LEV treatment, 78.0% also had a positive response to BRV treatment. Of the non-responders to LEV treatment, 46.2% did have a positive response to BRV treatment. In comparison to LEV, patients reported significantly fewer TEAEs during BRV treatment (86.5% vs 61.7%, p<0.05). The most substantial difference was seen in the category ‘behaviour’ (55.1% vs 22.4%, p<0.05). Newly found behavioural TEAEs after switching from LEV to BRV were found in 7.1% of patients. ConclusionOverall BRV was better tolerated than LEV, especially regarding the behavioural TEAEs. Efficacy analyses showed that patients are likely to have a positive response to BRV when they had a positive response to LEV. However, this is not always guaranteed. Lack of response to LEV does not preclude a positive response to BRV. All in all, BRV seems to be an interesting treatment option in patients previously treated with LEV.

Analysis of the clinical characteristics of the liver injury induced by levetiracetam.

Levetiracetam (LEV) has a low risk of hepatotoxicity due to low liver metabolism. Knowledge regarding the association between LEV exposure and liver injury is based mainly on case reports. The purpose of this study is to summarize the clinical features of LEV-induced liver injury. We collected literature on liver injury induced by LEV for retrospective analysis from 1999 to April 2021 in Chinese and English. The median age of 21 patients (13 males and 8 females) was 31 years (range 0.13-76). The median time for liver injury was 19 days (range 3-120). The clinical manifestations of patients ranged from asymptomatic elevated liver enzymes in 5 patients (23.8%) to fever, digestive system symptoms and skin rash in 16 patients (76.2%). The median values of alanine aminotransferase and aspartate aminotransferase were 773 IU/L (range 60-4800) and 667.5 IU/L (range 53-10 387), respectively. Liver biopsy demonstrated hepatocellular necrosis. The liver function returned to normal at a median time of 9 days (range 2-270) after discontinuation of LEV. LEV-induced liver injury is a rare adverse reaction, ranging from asymptomatic elevated transaminases to fulminant liver failure. Patients receiving long-term treatment with LEV should consider monitoring liver function.

Safety and Tolerability of Rapid Administration Undiluted Levetiracetam.

Levetiracetam (LEV) is an antiepileptic drug used widely in patients with a favorable safety profile. Studies evaluating the safety and efficacy of intravenous (IV) LEV included volumes of at least 100mL. Minimally diluted doses administered over 5-6min were found to be both safe and effective. Given the complexities of admixing, this practice can be impractical and result in delays in antiepileptic therapy. This study aimed to retrospectively review the safety and tolerability of rapid administration of undiluted LEV doses ≤ 1000mg. This was a retrospective study evaluating adverse drug reactions associated with undiluted LEV from January 1, 2018-June 1, 2018. Patients were included if they received at least one dose of undiluted LEV and were ≥ 18years old. Safety endpoints were reviewed and collected from the time administration until hospital discharge. Endpoints included injection site pain and discomfort, injection site erythema, extravasation, IV line replacement, and any documented adverse effect leading to IV LEV discontinuation. Descriptive statistics were used to analyze the data. A total of 199 patients were included in the study totaling 1626 doses of LEV. Most patients were administered LEV 1000mg (60.8%), through a peripheral line (64.3%), and were prescribed LEV for seizure prophylaxis (58.3%). Patients received a mean of 8.1 ± 8 doses for a mean duration of therapy of 5 ± 4.5days. About 98.5% of patients did not experience an adverse effect, whereas 1.5% of patients experienced agitation, delirium, confusion, and/or lethargy, which is well known to LEV therapy. Rapid administration of undiluted LEV doses ≤ 1000mg were well tolerated with no concentration-related side effects. Further prospective research is needed to confirm this observation as well as the safety of higher doses.

Levetiracetam‐induced thrombocytopenia in a patient with status epilepticus

Levetiracetam has broad-spectrum activity in epilepsy. In contrast to phenytoin, levetiracetam has an ideal pharmacokinetic profile without any severe haemodynamic side effects and therefore intravenous loading of levetiracetam is commonly used in adult patients with status epilepticus, especially those who have medical problems. However, levetiracetam-induced serious adverse effects, such as thrombocytopenia and pancytopenia, have been reported in the literature. Here, we describe a case of status epilepticus after cardiac arrest treated with levetiracetam in which severe thrombocytopenia developed and was successfully managed by discontinuation of levetiracetam. Our report aims to increase awareness of this rare cause of thrombocytopenia among clinicians and provide a review of the literature.

The Application of Density Spectral Array Monitoring in Digital Electroencephalography for Levetiracetam-Induced Non-Convulsive Status Epilepticus in a Patient with Lennox-Gastaut Syndrome

Objective: To analyze the density spectral array (DSA) on the digital electroencephalography (EEG) in a patient with Lennox-Gastaut syndrome (LGS) who developed non-convulsive status epilepticus (NCSE) after initiation of oral levetiracetam (LEV). Methods: Digital EEG was performed on the patient for a 30 min period during the daytime while he was asleep status without hypnotic drugs. The DSA, which incorporated a conventional program of the digital EEG, was sequentially evaluated. Result: The DSA demonstrated that the continuous and periodic high voltages and broad ranges of oscillation, reflecting epileptic activity and the clinical conditions. The EEG demonstrated obvious bilateral frontopolar and/or diffuses 2-3 Hz slow spike-and-wave complex activities, which were not evident before initiation of LEV. Development of LEV-induced NCSE was suspected. Discontinuation of LEV and increasing the dose of clobazam resulted in recovery from NCSE, followed by gradual restoration of the original DSA and EEG findings. Conclusion: On administering of LEV for patients with LGS, the occurrence of NCSE should be carefully monitored. The DSA based on digital EEG was useful for both the diagnosis of NCSE as a drug side-effect and the recovery from its epileptic status.

Efficacy of levetiracetam as first add-on therapy to carbamazepine and valproate sodium for children with epilepsy

We examined the effectiveness of levetiracetam (LEV) as add-on therapy after failed treatment with a first anti-epileptic drug in a prospective cohort of children with epilepsy. Eligible patients with epilepsy experienced uncontrolled seizures with the first anti-epileptic drug and were 1-15-year-old. Afte ra3m obaseline period, patients were administered LEV at an initial dose of 10 mg/kg/d, which, if needed, was incrementally increased by 5 mg/kg/d weekly up to a maximum dose of 60 mg/kg/d. Seizure frequency was defined as the mean seizure frequency per month. Clinical response to LEV over the following period of at least 6 mo was divided into five categories. A total of 37 patients were enrolled. The majority of patients (97.30%) had localization-related epilepsy. The responder rate (rate of patients with ≥50% reduction in seizure frequency) was 30/37 (81.08%). In addition, 20 of 37 (54.05%) patients showed complete seizure cessation. Mean percentage reduction in seizure frequency (all types of seizures) during the first 6 mo treatment period compared to baseline was 89.28% in responders, compared with 25.22% in non-responders. This proportion remained stable during the second 6 mo period (90.17%). Significant changes in seizure frequency were seen between before LEV administration and both the first 6 mo (P < 0.01) and second 6 mo (P < 0.01) in responders, but not in non-responders. Mean effective dose of LEV was 27.51 mg/kg/d. Somnolence was the only reported individual adverse event (5.41%), and was mild in all cases, so LEV discontinuation was not needed. LEV appears useful as a first add-on treatment in children with localization-related epilepsy.

Possible levetiracetam induced encephalopathy presenting as electrical status epilepticus: An unknown occurrence

Levetiracetam is a novel, broad spectrum anti-epileptic drug with proven efficacy in generalized as well as focal onset seizures. It has renal elimination with no hepatic metabolism. Levetiracetam induced encephalopathy is rarely reported in literature. Triphasic waves in the electroencephalogram are seen in toxic-metabolic encephalopathies of various aetiology like hepatic encephalopathy, uraemia. We report a patient who was on levetiracetam for acute symptomatic seizures and developed encephalopathy with electroencephalogram showing generalised triphasic waves. These triphasic waves disappeared with intravenous lorazepam but without clinical improvement in sensorium. The electroencephalographic abnormality appeared as electrical status epilepticus which got normalised on discontinuation of levetiracetam. This is the first report of levetiracetam induced encephalopathy presenting as electrical status epilepticus and also depicts electroencephalographic correlate of levetiracetam induced encephalopathy.

Creatine phosphokinase elevation exacerbated by levetiracetam therapy.

A 19-year-old muscular male with a history of epilepsy presented following two convulsive events. Levetiracetam (LEV) was given as an additional therapy, resulting in a marked boost in creatine phosphokinase (CPK) that could not easily be explained by renal dysfunction or rhabdomyolysis alone. Levetiracetam discontinuation caused CPK levels to quickly normalize and should be considered in patients with persisting CPK elevations postconvulsive seizure.

Acute pancreatitis and elevated liver transaminases after rapid titration of oral levetiracetam

We report a 25-year-old woman with new onset convulsive episodes. The patient initially failed to respond to phenytoin and was switched to levetiracetam (LEV) which was rapidly titrated to 3000mg daily over 1week. At initiation of LEV therapy, she developed mild nausea and decrease in appetite. This was rapidly followed by severe digestive symptoms consistent with acute pancreatitis. She was also found to have elevated liver transaminases. An extensive work-up failed to reveal an organic cause for her symptoms, suggesting a direct relationship to LEV. Clinical symptoms and laboratory abnormalities normalized after LEV discontinuation, along with supportive therapy.

Continuation rates of levetiracetam in children from the EULEVp cohort study

BackgroundSince indication extension to children data regarding the effectiveness of levetiracetam in paediatric patients remains limited. AimsInvestigate the real-life effectiveness of levetiracetam in paediatric patients. MethodsEpileptic children (<16 years) who had initiated levetiracetam between the 1 October 2006 and the 31 March 2007 were included and followed for 1 year by hospital or non-hospital neurologists practising in France. ResultsAmong the 156 identified children, 147 were analysed: 51.7% were female, and mean (SD) age was 9.2 years (4.2). Most patients had either partial symptomatic (30.6%) or partial cryptogenic (26.5%) epilepsy, 92.5% experienced seizures during the 6 months preceding levetiracetam initiation, and 19.2% were on levetiracetam alone at initiation. One-year levetiracetam continuation rate was estimated to be 72.0% (95%CI [63.8; 78.6]). Of the 104 children continuing levetiracetam treatment at end of study, 31.7% were seizure-free during the last six months of follow-up, and 23.1% on levetiracetam alone. Discontinuation of levetiracetam (n = 41) was mainly for insufficient efficacy (58.5% of those concerned). ConclusionsIn real-life clinical practice important treatment retention and non-negligible reduction of seizure frequency may be expected.

Efficacy and safety of add-on levetiracetam in refractory childhood epilepsy

Purpose: The purpose of the present study was to evaluate the efficacy and safety of levetiracetam (LEV) in refractory epileptic children. Methods: The study group included 61 outpatients (7 generalized, 48 localization-related, 3 undetermined, 3 unclassified) aged between 16months and 18years. LEV was given twice daily at a total dose of 10mg/kg/day. The final mean dose was 50.7mg/kg/day. The mean number of prior anti-epileptic drugs was 5.2. The entire treatment period was more than 6months after LEV administration. Results: Fifteen children (24.6%) became seizure-free for 6months after starting LEV, and 18 (29.5%) had a seizure reduction of more than 50% for the entire 6months. The response rate was 33/61 (54.1%). Responders included 2/3 of patients (66.7%) with epilepsy with continuous spikes and waves during slow sleep and 13/19 (68.4%) with frontal lobe epilepsy. The effective dosage of LEV in the responders demonstrated a wide range (mean, 46.1mg/kg/day; range, 19.4–59.1mg/kg/day), and showed bimodal distribution. Adverse events occurred in only two patients who did not require LEV discontinuation. Conclusion: LEV represents an important addition to the treatments available for refractory epileptic children.

The EULEV cohort study: rates of and factors associated with continuation of levetiracetam after 1 year

Levetiracetam has shown good safety/tolerability and efficacy in regulatory trials. This was confirmed in observational investigations performed soon after marketing by using continuation or retention rates as a composite measure. When an anti-epileptic drug first becomes available; however, there is evidence of channelling to more severe patients than thereafter. This study was performed several years after marketing of levetiracetam and found high rates of continuation. It also further explores this measure by determining the continuation in the absence of initiation of additional anti-epileptic drugs. To investigate real-life effectiveness of levetiracetam in patients initiating treatment in a stable market situation. Epileptic adults who had initiated levetiracetam between 1 January and 31 August in 2005 or 2006 were included and followed for 1 year by hospital or nonhospital neurologists practising in France. One-year continuation rates were estimated using Kaplan-Meier analysis. Among those still treated at end of study, treatment goals were investigated. Factors associated with discontinuation were investigated using Cox proportional hazards regression. A total of 794 subjects were included in the cohort, and 753 subjects were followed up and included in the analysis. Among these, mean (SD) age was 42.6 (±17.0) years, 51.1% were female, 76.6% had partial epilepsy, 93.5% had seizures in the 6 months preceding levetiracetam initiation and 82.9% had at least one concomitant anti-epileptic drug when starting levetiracetam. One-year levetiracetam continuation rate was 83.5% (95% confidence interval, 80.5-86.0%). Of the 579 patients still using levetiracetam at end of study, 46.8% were seizure free during the last 6 months, and 24% were on levetiracetam monotherapy. Reasons for discontinuation (n= 122) were adverse events (45%), lack of efficacy (38%) or both (9%). Levetiracetam discontinuation was most strongly associated with previous exposure to more than four anti-epileptic drugs, whereas continuation was most strongly associated with presence of seizure-related falls in the 6 months preceding levetiracetam initiation. This population-based cohort study in a stable market situation found a high 1 year levetiracetam continuation rate compared with previous studies done sooner after market introduction.

Levetiracetam in Childhood Epilepsy

Levetiracetam is an antiepileptic drug that has been shown to be effective in various types of seizures, both partial and generalized. Although it is not yet well established because of the small number of studies, levetiracetam as both add-on therapy and monotherapy can be considered as an alternative to valproic acid in some pediatric patients. We have reviewed the available data on the efficacy, tolerability, and safety of levetiracetam in children with epilepsy. The efficacy of levetiracetam as an adjunctive therapy and as monotherapy for generalized and partial childhood epilepsies and for some types of specific epileptic syndromes of infancy and childhood (such as juvenile myoclonic epilepsy, benign rolandic epilepsy, and Jeavon syndrome) has been demonstrated in some studies. Moreover, levetiracetam may be a valuable option for children with refractory epilepsy. The reported tolerability of levetiracetam and its safety profile are favorable. Among the side effects reported, behavioral changes and even psychotic reactions seem to occur more frequently in younger patients (under 4 years of age). The onset of signs/symptoms usually occurs early, even during the titration phase, and, in many cases, at a low dosage (<20 mg/kg/day). These side effects were always observed to be reversible after discontinuation of levetiracetam. In conclusion, results from clinical trials to date suggest that levetiracetam has a full spectrum of efficacy as well as a favorable safety profile, and this drug can be considered a valuable option in the treatment of epilepsy in pediatric patients.

Generalized seizures aggravated by levetiracetam in an adult patient with phenylketonuria

Phenylketonuria (PKU) is one of the most common inherited metabolic disorders, which is characterized by excessive accumulation of phenylalanine (Phe) in tissues. Generalized seizures occur in 25% of the patients. Little is known about seizures and their treatment in adult PKU patients, and information with newer antiepileptic drugs is lacking. Here we report an adult patient who developed generalized seizures later in life, despite strict dietary control, and whose seizures were aggravated by levetiracetam (LEV). Convulsions ceased after discontinuation of LEV and the patient has been seizure free on topiramate 125 mg/day.

Pancytopenia Associated with Levetiracetam Treatment

Levetiracetam is a pyrrolidine derivate that is approved for the treatment of seizures. It has a favourable pharmacokinetic profile, no clearly established pharmacological interactions, good tolerability and offers the possibility of rapid treatment. We describe a case of pancytopenia and multiple infections observed in the context of levetiracetam treatment. A 65-year-old woman who underwent surgical removal of a meningioma developed progressive pancytopenia complicated by pneumonia and multiple liver abscesses after starting levetiracetam therapy. Bone marrow aspiration and biopsy confirmed the diagnosis. A gradual spontaneous recovery of normal haematopoiesis followed discontinuation of levetiracetam.

Levetiracetam Induced Interstitial Nephritis and Renal Failure

A 17-year-old girl who had started on levetiracetam because of new onset partial complex seizures developed acute renal failure and biopsy-confirmed interstitial nephritis 10 days after starting the drug. She made a complete and rapid recovery after discontinuation of levetiracetam and administration of oral corticosteroids. Levetiracetam, known to be predominantly excreted by the kidneys, has not previously been reported to cause significant renal complications in children. Children taking levetiracetam who present with abdominal pain, malaise, vomiting, oliguria, rash, or urticaria may require screening laboratory evaluation for potential renal adverse effects.

Encephalopathy induced by levetiracetam added to valproate

We report on the manifestation of a levetiracetam (LEV)-induced encephalopathy. A 28-year-old man suffering from idiopathic epilepsy with generalized seizures was treated with LEV (3000 mg) added to valproate (VPA) (2000 mg). Frequency of generalized tonic-clonic seizures increased from one per 6 months to two per month. Neuropsychological testing showed impaired word fluency, psychomotor speed and working memory. The interictal electroencephalogram (EEG) showed a generalized slowing to 5 per second theta rhythms with bilateral generalized high-amplitude discharges. Following discontinuation of LEV, EEG and neuropsychological findings improved and seizure frequency decreased.