Rates of Adverse Events and Outcomes among Stroke Patients Admitted to Primary Stroke Centers.

BACKGROUND AND PURPOSE: To identify the beneficial effects of primary stroke centers (PSCs) certification by Joint Commission (JC), we compared the rates of in-hospital adverse events and discharge outcomes among ischemic stroke patients admitted to PSCs and those admitted to non-PSC hospitals in the United States. METHODS: We obtained the data from the Nationwide Inpatient Sample from 2010 and 2011. The analysis was limited to states that publicly reported hospital identity. PSCs were identified by matching the Nationwide Inpatient Sample hospital files with the list provided by JC. The analysis was limited to patients (age ≥18 years) discharged with a principal diagnosis of ischemic stroke (International Classification of Disease, 9th Revision, codes 433.x1, 434.x1). RESULTS: We identified a total of 123,131 ischemic stroke patients from 28 states. A total of 72,982 (59.3%) patients were admitted to PSCs. After adjusting for age, gender, race or ethnicity, comorbidities, All Patients Refined Diagnosis Related Groups (APR-DRG)-based disease severity, and hospital teaching status, patients admitted to PSCs were at lower risk of in-hospital adverse events complications: pneumonia (odds ratio [OR], .8; 95% confidence interval [CI], .7-.8) and sepsis (OR, .7; 95% CI, .6-.8). Patients admitted to PSCs were more likely to receive thrombolysis (OR, 1.6; 95% CI, 1.5-1.7). The mean cost of hospitalization (95% CI) of the patients was significantly higher in patients admitted at PSCs compared with those admitted at non PSC hospitals $47621 (47099-48144) vs. $35229 (34803-35654), P < .0001). The patients admitted to PSCs had lower inpatient mortality (OR, .8; 95% CI, .8-.9) and were more likely to be discharged with none to minimal disability (OR, 1.1; 95% CI, 1.0-1.1). CONCLUSIONS: Compared with non-PSC admissions, patients admitted to PSCs are less likely to experience hospital adverse events and more likely to experience better discharge outcomes.

Neuroprotective effect of asiatic acid in rat model of focal embolic stroke.

Asiatic acid (AA) is a pleiotropic neuroprotective agent that has been shown to attenuate infarct volume in mouse and rat models of focal ischemia and has a long clinically relevant therapeutic time-window. Because in a future trial AA would be administered with tissue-plasminogen activator (t-PA), the only approved acute stroke therapy, we sought to determine the effect of AA when co-administered with t-PA in a rat focal embolic stroke model. Male rats were treated with AA (75 mg/kg) alone, low-dose t-PA (2.5 mg/kg) alone, or a combination of AA and low-dose t-PA at 3 h after inducing embolic stroke. AA significantly reduced infarct volume whereas low-dose t-PA alone did not reduce infarct volume compared with vehicle. Significantly, combination treatment further enhanced reduction of infarct volume versus AA alone. Treatment with AA reduced cytochrome c (CytoC) and apoptosis-inducing factor (AIF) release from brain mitochondria after ischemia. AA was also neuroprotective against L-glutamate-induced toxicity in primary cortical neurons. In summary, combination treatment with AA and low-dose t-PA at 3 h after embolic stroke reduces infarct volume, improves neurological outcome, and provides neuroprotection. The neuroprotective effects of AA were partially associated with reduction of AIF and CytoC release.

Medicolegal considerations with intravenous tissue plasminogen activator in stroke: a systematic review.

Background. Intravenous tPA (tissue plasminogen activator) therapy remains underutilized in patients with Acute Ischemic Stroke (AIS). Anecdotal data indicates that physicians are increasingly liable for administering and for failure to administer tPA. Methods. An extensive search of Medline, Embase, Westlaw, LexisNexis Legal, and Google Scholar databases was performed. Case studies that involved malpractice litigation in ischemic stroke and thrombolytic therapy were analyzed systematically. Results. We identified 789 ischemic stroke litigation cases, of which 46 cases were related to intravenous tPA and stroke litigation. Case descriptions of 40 cases were available. Data for verdicts were available for 38 patients. The most frequent plaintiff claim was related to failure to administer intravenous tPA (38, 95%). Only 2 (5.0%) claim involved complications of treatment with tPA. Hospitals were defendants in majority of the 36 cases. Physicians were involved in 33 cases. While ED physicians were involved in 25 (60.52%) cases, neurologists were involved in 8 (20.0%) cases. There were 26 (65%) defendant-favored and 12 (30%) plaintiff-favored verdicts. Conclusion. Physicians and hospitals are at an increased risk of litigation in patients with AIS when in IV-tPA is being considered for treatment. While majority of the cases litigated were cases where tPA was not administered, only about 1 in 20 cases was litigated when complications occurred.

Lymphocyte cell kinase activation mediates neuroprotection during ischemic preconditioning.

The molecular mechanisms underlying preconditioning (PC), a powerful endogenous neuroprotective phenomenon, remain to be fully elucidated. Once identified, these endogenous mechanisms could be manipulated for therapeutic gain. We investigated whether lymphocyte cell kinase (Lck), a member of the Src kinases family, mediates PC. We used both in vitro primary cortical neurons and in vivo mouse cerebral focal ischemia models of preconditioning, cellular injury, and neuroprotection. Genetically engineered mice deficient in Lck, gene silencing using siRNA, and pharmacological approaches were used. Cortical neurons preconditioned with sublethal exposure to NMDA or oxygen glucose deprivation (OGD) exhibited enhanced Lck kinase activity, and were resistant to injury on subsequent exposure to lethal levels of NMDA or OGD. Lck gene silencing using siRNA abolished tolerance against both stimuli. Lck-/- mice or neurons isolated from Lck-/- mice did not exhibit PC-induced tolerance. An Lck antagonist administered to wild-type mice significantly attenuated the neuroprotective effect of PC in the mouse focal ischemia model. Using pharmacological and gene silencing strategies, we also showed that PKCε is an upstream regulator of Lck, and Fyn is a downstream target of Lck. We have discovered that Lck plays an essential role in PC in both cellular and animal models of stroke. Our data also show that the PKCε-Lck-Fyn axis is a key mediator of PC. These findings provide new opportunities for stroke therapy development.

Asiatic acid attenuates infarct volume, mitochondrial dysfunction, and matrix metalloproteinase-9 induction after focal cerebral ischemia.

BACKGROUND AND PURPOSE: Asiatic acid (AA) has been shown to attenuate cerebral infarction in a mouse model of focal ischemia and shows promise as a neuroprotective stroke therapy. To facilitate translation of these findings to clinical studies, we determined pharmacokinetics, a dose-response relationship, the therapeutic time window, and efficacy using multiple stroke models. We also explored potential mechanisms of action. METHODS: Escalating doses of intravenous AA were administered and serum concentrations were measured at multiple time points for the pharmacokinetic studies. Subsequently, a dose-response relationship was determined followed by administration at different intervals after the onset of ischemia to establish a therapeutic time window for neuroprotection. Outcome measurements included both histological and behavioral. Mitochondrial function and matrix metalloproteinase activity in controls and treated rats were also determined. RESULTS: The pharmacokinetic studies showed that AA (75 mg/kg) has a half-life of 2.0 hours. AA significantly decreased infarct volume and improved neurological outcome even when administration was at time points up to 12 hours after the onset of ischemia. Infarct volume was also significantly decreased in female rats and spontaneously hypertensive rats. AA attenuated mitochondrial dysfunction and reduced matrix metalloproteinase-9 induction. CONCLUSIONS: Our study shows AA is effective against multiple models of focal ischemia, has a long therapeutic time window, and is also effective in females and hypertensive animals. AA may mediate neuroprotection by protecting mitochondria and inhibiting matrix metalloproteinase-9 induction and activation. Taken together these data suggest that AA is an excellent candidate for development as a stroke therapy.

ABCD2 Score and Large-Artery Atherosclerosis.

BACKGROUND AND PURPOSE: Extracranial stenosis (ECS) or intracranial stenosis (ICS) are independent risk factors for stroke after transient ischemic attack (TIA). We examined the association of the age, blood pressure, clinical features, duration of symptoms and diabetes (ABCD2) score, a validated risk prediction model for stroke after TIA, and the presence of ICS or ECS. METHODS: Vascular imaging and ABCD2 scores were obtained in a retrospective cohort of 77 consecutive patients diagnosed with TIA in a single center emergency department. The association between vascular stenosis and ABCD2 scores and how each related to clinical outcome was examined. RESULTS: In all, 30 (39.2%) TIA patients had 37 stenotic lesions; 15 (40.5%) stenotic lesions were ICS and 22 (59.5%) stenotic lesions were ECS. A total of 7 patients (9.5%) had both ECS and ICS lesions. Patients with ABCD2 > 3 were more likely to have ICS (odds ratio [OR] = 6.25, confidence interval [CI] 1.39-32.44, P = .009) and ECS (OR = 5.25, CI = 1.56-17.66, P = .005). Of the 37 stenotic lesions, 21 (56.7%) were symptomatic; 4 (19.2%) of these had an ABCD2 ≤ 3. At 7 days, there were 4 ischemic strokes, 3 had previously demonstrated symptomatic stenotic lesions, and all had ABCD2 scores > 3. CONCLUSIONS: Compared to patients in the low-risk ABCD2 scores, the patients with medium- to high-risk ABCD2 scores are more likely to have symptomatic and asymptomatic vascular stenotic lesions. However, 1 in 5 patients with low-risk ABCD2 score has symptomatic stenotic lesions, indicating ABCD2 score does not identify all patients with symptomatic stenotic lesions.

Neuroprotective effect of cyanidin-3-O-glucoside anthocyanin in mice with focal cerebral ischemia.

The present study sought to determine the neuroprotective effect of anthocyanin cyanidin-3-O-glucoside (CG), isolated and purified from tart cherries, against permanent middle cerebral artery occlusion (pMCAO) in mice and its potential mechanisms of neuroprotection. C57BL/6 mice subjected to pMCAO were treated with CG orally. Twenty-four hours after pMCAO, neurological scoring was used to evaluate functional outcome. The brains were then excised for measuring infarct volume and brain superoxide levels were determined. In a separate set of experiments, the influence of CG on cytochrome c (cyt c) and apoptosis-inducing factor (AIF) release from mitochondria under oxidative stress were assessed in isolated cortical neurons from adult mouse brains. Infarction volume was attenuated by 27% in mice pre-treated with 2mg/kg of CG compared to vehicle-treated mice. Delayed treatment with 2mg/kg of CG also showed 25% reduction in infarct size. Neurological functional outcome was significantly improved in mice pre- or post-treated with CG. Compared to vehicle treated mice CG treated mice had lower levels of brain superoxide. CG also blocked the release of AIF from mitochondria under oxidative stress, but did not inhibit the release of cyt c. Our data show that CG is neuroprotective against pMCAO in mice, and this beneficial effect may be mediated by attenuation of brain superoxide levels after ischemia. CG may also exert its neuroprotective effect by blocking AIF release in mitochondria.

Wallenberg's syndrome with extradural-extracranial origin of the posterior inferior cerebellar artery.

We report a case of lateral medullary syndrome (LMS) with extradural origin of the posterior inferior cerebellar artery (PICA). A 45-year-old construction worker presented with acute signs and symptoms of typical LMS. Prolonged work-related neck extension was reported just prior to the onset of symptoms. Cerebral angiography revealed a patent vertebrobasilar tree with an extradural origin of an otherwise normal appearing PICA ipsilaterally. Workup did not show evidence for cardioembolic or atheroembolic source. The presence of an extradural origin of PICA may be considered a predisposing factor for non-traumatic LMS associated with head and neck movement.

Predictors of occult paroxysmal atrial fibrillation in cryptogenic strokes detected by long-term noninvasive cardiac monitoring.

Background and Purpose. Paroxysmal Atrial fibrillation/Flutter (PAF) detection rates in cryptogenic strokes have been variable. We sought to determine the percentage of patients with cryptogenic stroke who had PAF on prolonged non-invasive cardiac monitoring. Methods and Results. Sixty-two consecutive patients with stroke and TIA in a single center with a mean age of 61 (+/- 14) years were analyzed. PAF was detected in 15 (24%) patients. Only one patient reported symptoms of shortness of breath during the episode of PAF while on monitoring, and 71 (97%) of these 73 episodes were asymptomatic. A regression analysis revealed that the presence of PVCs (ventricular premature beats) lasting more than 2 minutes (OR 6.3, 95% CI, 1.11-18.92; P = .042) and strokes (high signal on Diffusion Weighted Imaging) (OR 4.3, 95% CI, 5-36.3; P = .041) predicted PAF. Patients with multiple DWI signals were more likely than solitary signals to have PAF (OR 11.1, 95% CI, 2.5-48.5, P < .01). Conclusion. Occult PAF is common in cryptogenic strokes, and is often asymptomatic. Our data suggests that up to one in five patients with suspected cryptogenic strokes and TIAs have PAF, especially if they have PVCs and multiple high DWI signals on MRI.

Clinical significance of serum zinc levels in cerebral ischemia.

Background. Zinc mediates several vital physiological, enzymatic and cellular functions. The association between serum zinc and stroke outcome has not been previously evaluated. Methods. This single center retrospective study was conducted on consecutive stroke (n = 158) and TIA (n = 74) patients. We sought to determine whether serum zinc concentrations in patients with acute ischemic strokes were associated with stroke severity and poor functional status at discharge, respectively. Results. Overall, out of the 224 patients analyzed (mean age 67 years), 35.7% patients had low zinc levels (65 mcg/dL). Patients with stroke (n = 152) were more likely to have low zinc levels (OR = 2.62, CI 1.92-3.57, P < .003) compared to patients with TIA (n = 72). For patients with stroke (n = 152), multivariate analysis showed that low serum zinc levels (OR 2.82, CI 1.35-5.91, P = .035) and strokes with admission severe strokes (NIHSS > 8) (OR 2.68, CI 1.1-6.5, P = .03) were independently associated with poor functional status (MRS > 3) at discharge from the hospital. Conclusion. Low serum zinc concentrations are associated with more severe strokes on admission and poor functional status at discharge.

Peripheral neuropathy: differential diagnosis and management.

Peripheral neuropathy has a variety of systemic, metabolic, and toxic causes. The most common treatable causes include diabetes mellitus, hypothyroidism, and nutritional deficiencies. The diagnosis requires careful clinical assessment, judicious laboratory testing, and electrodiagnostic studies or nerve biopsy if the diagnosis remains unclear. A systematic approach begins with localization of the lesion to the peripheral nerves, identification of the underlying etiology, and exclusion of potentially treatable causes. Initial blood tests should include a complete blood count, comprehensive metabolic profile, and measurement of erythrocyte sedimentation rate and fasting blood glucose, vitamin B12, and thyroid-stimulating hormone levels; specialized tests should be ordered if clinically indicated. Lumbar puncture and cerebrospinal fluid analysis may be helpful in the diagnosis of Guillain-Barré syndrome and chronic inflammatory demyelinating neuropathy. Electrodiagnostic studies, including nerve conduction studies and electromyography, can help in the differentiation of axonal versus demyelinating or mixed neuropathy. Treatment should address the underlying disease process, correct any nutritional deficiencies, and provide symptomatic treatment.

Elevated levels of pre-procedural high-sensitivity C-reactive protein is associated with midterm restenosis after extra- and intracranial stenting.

BACKGROUND AND PURPOSE: High-sensitivity C-reactive protein (hsCRP) is an inflammatory marker associated with subsequent coronary events and neointimal hyperplasia after coronary artery stent placement. We sought to determine if elevated levels of hsCRP are associated with restenosis after placement of extra- and intracranial stents. METHODS: We retrospectively reviewed 73 consecutive patients at Michigan State University from July 2006 until June 2007 who underwent treatment with carotid artery stent placement or intracranial stent placement. Data were collected in regards to demographics, pre-procedural hsCRP, and LDL levels, and angiographic variables characterizing the lesion before and after treatment. A binary logistic regression model was constructed to determine independent predictors of restenosis. RESULTS: A total of 73 patients with a mean age of 69 +/- 11 years were studied. A total of 57 patients were treated with extracranial carotid stenting, 22 (38%) of whom were symptomatic, while 16 patients underwent intracranial stenting (all were symptomatic). There were 9 patients (4 intracranial stents [25%] and 5 carotid stents [8.8%]) who developed a restenosis of >50%. In binary logistic regression modeling, the following variables were found to be independently predictive of developing restenosis: smaller vessel diameter (OR .49, 95% CI .23-.98, P-value .046) and elevated hsCRP (OR 2.2, 95% CI 1.29-6.66, P-value .018). CONCLUSIONS: Elevated levels of pre-procedural hsCRP may be predictive of the development of neointimal hyperplasia in patients treated with extra- or intracranial stenting procedures. Future prospective multicenter studies will be required to confirm these findings.

Cardiovascular complications of the Guillain-Barré syndrome.

The Guillain-Barré syndrome (GBS) is the most common cause of acute flaccid paralysis in young adults and the elderly and an important cause of admission to intensive care units. Manifestations of the GBS vary from monoparesis to life-threatening paralysis of the respiratory muscles. The latter is often punctuated by the presence of cardiac involvement. This ranges from variations in blood pressure to involvement of the myocardium and potentially fatal arrhythmias. This review addresses some of the common cardiovascular complications of the GBS, with their myriad presentations and therapeutic options, as well as potential preventive measures that can be helpful in the management of patients admitted to intensive care units. In conclusion, it is necessary to recognize the potentially fatal cardiovascular complications associated with the GBS and treat them accordingly.

Blood pressure changes after intravenous fosphenytoin and levetiracetam in patients with acute cerebral symptoms.

PURPOSE: To study the incidence and extent of the occasionally noted hypotension after intravenous (IV) infusions of fosphenytoin (FOS) and levetiracetam (LEV) in patients presenting with acute cerebral symptoms. METHODS: Retrospective data collection of consecutive patients with acute cerebral symptoms who received IV infusions of a single dose of 750 mg or more of either fosphenytoin or levetiracetam and had documented blood pressure values in the 2h prior and the 2h after their IV infusion. RESULTS: More than 10 mmHg drop in the systolic, diastolic and MBP was observed in the FOS group following the IV infusion (-16.82 mmHg, -11.60 mmHg, and 13.34 mmHg, respectively). However, there was not a significant change in the MBP after LEV infusion (1.54 mmHg, 1.84 mmHg, and 1.74 mmHg for systolic, diastolic and MBP change, respectively). The difference in the systolic, diastolic and MBP changes between the two groups was statistical significant (all p values are <0.0001) after adjusting for age, clinical presentations of the patients and if they were on any antihypertensive medication in the hospital. Sixty two percent of patients who received FOS had >10 mmHg decrease in their MBP. In the LEV group, only 2 of the 50 patients (4%) had >10 mmHg decrease in their MBP. The difference in proportion of the patients with >10 mmHg drop in MBP between the two study groups is also statistically significant (p<0.001) for age, clinical presentations of the patients and if they were on any antihypertensive medication in the hospital. CONCLUSIONS: IV infusion of FOS in subjects presenting with acute cerebral symptoms may cause significant decreases in their blood pressure. This was not seen in patients receiving IV LEV infusions. Since maintaining adequate cerebral perfusion pressure is a key point in the management of patients with acute cerebral symptoms, the results of this study may carry a clinical impact on the management of this subgroup of patients.

Diffusion-weighted imaging: not all that glitters is gold.

Diffusion-weighted imaging (DWI) is a sophisticated magnetic resonance imaging (MRI) technique with rapid acquisition time and high sensitivity for depicting acute cerebral ischemia. It is currently part of the routine workup in most medical centers when ischemic stroke is in the differential diagnosis. DWI helps establish a diagnosis of acute ischemic infarct even in cases where the clinical presentation is not typical for ischemic stroke. However, contrary to popular belief, not every hyperintensity on DWI is an ischemic stroke. Consequently, DWI with high intensity signals, commonly called "positive" DWI, is sometimes misinterpreted and leads to incorrect medical management. In this report, we briefly discuss some of the essential, technical aspects of DWI and report various clinical scenarios, which may lead to "positive" DWI findings but are not ischemic strokes. Although the sensitivity of DWI for ischemic stroke is very high, the specificity is not as high, and a "positive" DWI does not exclude other diagnoses that should be considered based on each patient's clinical history and examination, and the appearance of other sequences of MRI scans.

Extent of intra-arterial calcification on head CT is predictive of the degree of intracranial atherosclerosis on digital subtraction angiography.

BACKGROUND: Intracranial intra-arterial calcifications (ICAC) are a common finding on head CT examinations, but their significance is not known. The aim of this study is to determine if a relationship exists between ICAC on head CT and the presence of a high-grade atherosclerotic stenosis on cerebral angiography. METHODS: This was a retrospective study of 108 consecutive patients admitted to the stroke service at Parkland Hospital in Dallas, Tex., USA. Each patient had undergone a head CT and catheter-based angiographic study to meet the inclusion criteria. Demographic information was recorded along with CT imaging data in regards to the amount of calcification. Angiographic images were reviewed independently, and a comparison was made to determine if calcification was predictive of finding a high-grade stenosis on angiography. RESULTS: A total of 108 consecutive patients with a mean age of 56 +/- 12 years were studied. Of the 540 vessels studied, 65 (12%) were found to have a stenosis of >or=50% on angiography, and 71 (13.1%) were found to have a calcium grade of 3 or 4 on head CT. ICAC appeared to be more common in the anterior circulation compared to the posterior circulation. Patients with grade 3 or 4 calcification of an intracranial vessel on head CT were more likely to have a stenosis of >or=50% on cerebral angiography. CONCLUSIONS: The presence of ICAC on head CT appears to correlate with the presence of an underlying intracranial stenosis on angiography. Further study is required to validate these preliminary findings.

Cardiac dysfunction after left permanent cerebral focal ischemia: the brain and heart connection.

BACKGROUND AND PURPOSE: Stroke can lead to cerebrogenic cardiac arrhythmias. We sought to investigate the effect of ischemic stroke on cardiac function in a mouse model of permanent middle cerebral artery occlusion (pMCAO). METHODS: Twenty-four hours after the induction of focal ischemia, cardiac function was measured in mice by endovascular catheterization of the heart. Immediately after hemodynamic measurements, mice were euthanized and brains were excised and sectioned to measure infarct volume and the severity of insular cortex injury. Myocardial damage was evaluated by hematoxylin-eosin staining. Serum and heart levels of norepinephrine (NE) were also determined. RESULTS: Cardiac dysfunction occurred in 9 out of 14 mice that underwent left pMCAO. In these 9 mice, the severity of left insular cortex lesion was greater than the mice with normal heart function. The serum and heart levels of NE were significantly higher in left pMCAO mice with heart dysfunction. Liner regression analysis indicates significant inverse correlation between the severity of left insular cortex damage and heart dysfunction. Mice that underwent right pMCAO did not exhibit cardiac dysfunction. CONCLUSIONS: This study shows that left focal cerebral ischemia can produce cardiac dysfunction, which is associated with the extent of left insular cortex damage. Furthermore, mice exhibiting cardiac dysfunction had elevated levels of NE in the serum and heart.

Asiatic acid, a pentacyclic triterpene from Centella asiatica, is neuroprotective in a mouse model of focal cerebral ischemia.

Asiatic acid, a triterpenoid derivative from Centella asiatica, has shown biological effects such as antioxidant, antiinflammatory, and protection against glutamate- or beta-amyloid-induced neurotoxicity. We investigated the neuroprotective effect of asiatic acid in a mouse model of permanent cerebral ischemia. Various doses of asiatic acid (30, 75, or 165 mg/kg) were administered orally at 1 hr pre- and 3, 10, and 20 hr postischemia, and infarct volume and behavioral deficits were evaluated at day 1 or 7 postischemia. IgG (blood-brain barrier integrity) and cytochrome c (apoptosis) immunostaining was carried out at 24 hr postischemia. The effect of asiatic acid on stress-induced cytochrome c release was examined in isolated mitochondrial fractions. Furthermore, its effects on cell viability and mitochondrial membrane potential were studied in HT-22 cells exposed to oxygen-glucose deprivation. Asiatic acid significantly reduced the infarct volume by 60% at day 1 and by 26% at day 7 postischemia and improved neurological outcome at 24 hr postischemia. Our studies also showed that the neuroprotective properties of asiatic acid might be mediated in part through decreased blood-brain barrier permeability and reduction in mitochondrial injury. The present study suggests that asiatic acid may be useful in the treatment of cerebral ischemia.

Levetiracetam for managing neurologic and psychiatric disorders.

PURPOSE: The role of levetiracetam in different epileptic, nonepileptic, neurologic, and psychiatric disorders is discussed. SUMMARY: Levetiracetam, an antiepileptic drug (AED), was first approved as an adjunctive therapy for the treatment of partial epilepsy in adults. It is currently being used in the treatment of multiple seizure disorders, including generalized tonic-clonic; absence; myoclonic, especially juvenile myoclonic; Lennox-Gastaut syndrome; and refractory epilepsy in children and adults. Data are emerging on possible uses of levetiracetam outside the realm of epilepsy because of its unique mechanisms of action. There is preliminary evidence about the efficacy of levetiracetam in the treatment of different psychiatric disorders, including anxiety, panic, stress, mood and bipolar, autism, and Tourette's syndrome. The most serious adverse effects associated with levetiracetam use are behavioral in nature and might be more common in patients with a history of psychiatric and neurobehavioral problems. CONCLUSION: Levetiracetam is an effective AED with potential benefits in other neurologic and psychiatric disorders. The benefit-risk ratio in an individual patient with a specific condition should be used to determine its optimal use. Levetiracetam's use in nonepileptic conditions is not recommended until more data become available from larger trials.