Piero Perucca

Publications (13)97.38 Total impact

• Article: The adverse effects of antiepileptic drugs differ in patients with migraine - Authors' reply.

  Frank G Gilliam, Piero Perucca
  The Lancet Neurology 11/2012; 11(11):935. · 23.46 Impact Factor
• Article: Adverse effects of antiepileptic drugs.

  Piero Perucca, Frank G Gilliam
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  ABSTRACT: More than 150 years after bromide was introduced as the first antiepileptic drug, adverse effects remain a leading cause of treatment failure and a major determinant of impaired health-related quality of life in people with epilepsy. Adverse effects can develop acutely or many years after starting treatment and can affect any organ or structure. In the past two decades, many efforts have been made to reduce the burden of antiepileptic drug toxicity. Several methods to screen and quantify adverse effects have been developed. Patient profiles associated with increased risk of specific adverse effects have been uncovered through advances in the areas of epidemiology and pharmacogenomics. Several new-generation antiepileptic drugs with improved tolerability profiles and reduced potential for drug interaction have been added to the therapeutic armamentarium. Overall, these advances have expanded the opportunities to tailor treatment with antiepileptic drugs, to enhance effectiveness and minimise the risk of toxic effects.
  The Lancet Neurology 09/2012; 11(9):792-802. · 23.46 Impact Factor
• Article: The adverse event profile of pregabalin across different disorders: a meta-analysis.

  Gaetano Zaccara, Piero Perucca, Pier Franco Gangemi
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  ABSTRACT: In a recent meta-analysis of 38 double-blind randomized controlled trials (RCTs) comparing pregabalin (PGB) to placebo, we found 20 adverse events (AEs) to be significantly associated with PGB treatment. In the present study, we evaluated whether the incidence of these 20 AEs differs across distinct disorders in which PGB was investigated. Among the 38 previously identified RCTs of PGB, we selected only those including a PGB 600 mg/day arm and subsequently classified them into four distinct groups according to the disorder in which PGB was investigated: (1) drug-resistant partial epilepsy, (2) psychiatric disorders, (3) fibromyalgia, and (4) neuropathic pain. We used risk differences (RDs) to quantify the placebo-corrected proportion of subjects discontinuing PGB due to intolerable AEs and to determine the placebo-corrected incidence of each of the 20 PGB AEs across the four disorders. Twenty-two RCTs were included in this study. Neither the proportion of subjects discontinuing PGB due to intolerable AEs nor the incidence of PGB AEs (with the exception of ataxia) differed significantly across the four disorders. Ataxia was more common in drug-resistant partial epilepsy compared to fibromyalgia. When limiting analyses to subjects on placebo, most vestibulo-cerebellar AEs (ataxia, diplopia, and blurred vision) were found to be more common in drug-resistant partial epilepsy compared to all other disorders. Diplopia and blurred vision were more common in epilepsy than in neuropathic pain; and ataxia had a higher incidence in epilepsy than in anxiety disorder and fibromyalgia. Among other CNS AEs, somnolence was more common in epilepsy compared to neuropathic pain and in anxiety disorders alone compared to neuropathic pain and fibromyalgia. Asthenia was also more common in epilepsy than in neuropathic pain and fibromyalgia. Although drug-resistant partial epilepsy is associated with a higher probability of developing vestibulo-cerebellar AEs, the risk for PGB toxicity does not differ across distinct disorders.
  European Journal of Clinical Pharmacology 01/2012; 68(6):903-12. · 2.85 Impact Factor
• Article: Response to first antiepileptic drug trial predicts health outcome in epilepsy.

  Piero Perucca, Dale C Hesdorffer, Frank G Gilliam
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  ABSTRACT: Failure to respond to the initial antiepileptic drug (AED) is a predictor of increased risk of pharmacoresistant epilepsy. Whether response to the first AED also predicts adverse health outcomes is unknown. This longitudinal study compared rates of major adverse health outcomes (loss of driving privileges, unemployment, divorce/separation, injury, emergency room admission, hospitalization, and death) in 33 patients who failed the first AED (cases) and 30 patients who became seizure-free with the first AED (controls). Patient data were obtained by chart review and confirmed through a structured interview with each subject at 5-7 years after starting AED treatment. We also assessed between-group differences in quality of life, depression, and adverse AED effects by using standardized instruments completed by each subject at the end of follow-up. The number of major adverse health outcomes was similarly high during the first year of AED treatment [mean ± standard deviation (SD) 2.64 ± 0.99 for cases and 2.50 ± 1.14 for controls], but thereafter decreased to a greater extent in controls than in cases (p < 0.001). Controls had a higher cumulative probability of experiencing ≥1 year free from major adverse health outcomes compared to cases (p = 0.002). Two cases died during the follow-up, both of sudden unexpected death. Cases had worse quality of life ratings than controls, whereas no significant between-group differences were found for measures of depression and adverse AED effects. In a post hoc analysis limited to cases, patients who became seizure-free with subsequent AED treatments showed for the first 4 years major adverse health outcome rates similar to those recorded in patients with persisting seizures. After 4 years, however, cases who achieved late seizure freedom tended to show a more favorable outcome. Patients with epilepsy failing the initial AED trial are at increased risk of experiencing adverse health outcomes, at least for the first 4 years after diagnosis. Incorporating these findings into clinical decision making may aid in reducing delays in surgical referrals for pharmacoresistant epilepsy.
  Epilepsia 12/2011; 52(12):2209-15. · 3.96 Impact Factor
• Article: Status epilepticus migrainosus: clinical, electrophysiologic, and imaging characteristics.

  Pasquale Striano, Vincenzo Belcastro, Pasquale Parisi, Piero Perucca, Michele Terzaghi, Raffaele Manni
  Neurology 02/2011; 76(8):761; author reply 761. · 8.31 Impact Factor
• Article: The adverse event profile of pregabalin: a systematic review and meta-analysis of randomized controlled trials.

  Gaetano Zaccara, Pierfranco Gangemi, Piero Perucca, Luigi Specchio
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  ABSTRACT: Despite the widespread use of antiepileptic drugs (AEDs) across different neurologic and psychiatric disorders, no study has systematically reviewed all available randomized controlled trials (RCTs) of a given AED to fully uncover its tolerability profile. We aimed at identifying treatment emergent adverse events (AEs) associated with pregabalin through a systematic review and meta-analysis of all available RCTs. We also assessed the association between serious AEs and pregabalin, and investigated whether pregabalin AEs display a dose-response relationship. We searched MEDLINE, EMBASE, and Cochrane CENTRAL to February 2010 for RCTs. Additional studies were identified from reference lists of retrieved papers and from online clinical databases. We selected placebo-controlled, double-blind RCTs investigating the therapeutic effects of pregabalin in adults with any condition. Studies had to include at least 20 subjects per arm and have a duration of at least 4 weeks. AEs were assessed for their association with pregabalin after identification/exclusion of synonyms, rare AEs, and nonassessable AEs due to methodologic limitations. We used relative risks (RRs) to assess the association of any [99% confidence intervals (CIs)] or serious AEs (95% CIs) with pregabalin, and risk differences (RDs, 95% CIs) to investigate dose-response relationships of pregabalin AEs. Thirty-eight RCTs were included in our study. Of 39 AEs, 20 (51%) were significantly associated with pregabalin (dizziness, vertigo, incoordination, balance disorder, ataxia, diplopia, blurred vision, amblyopia, tremor, somnolence, confusional state, disturbance in attention, thinking abnormal, euphoria, asthenia, fatigue, edema, peripheral edema, dry mouth, constipation). The highest RRs were found for cognition/coordination AEs. There was no significant association between serious AEs and pregabalin. There was a selective dose-response pattern in the onset of pregabalin AEs, with certain AEs appearing at lower doses than others. Individuals starting treatment with pregabalin are at increased risk for several AEs, particularly those affecting cognition/coordination. Pregabalin AEs appear according to a selective dose-response pattern, possibly reflecting the severity of dysfunction of distinct anatomic structures. These findings may aid clinicians in providing better patient management, and support the value of including in meta-analyses of AED tolerability profiles RCTs performed in different conditions.
  Epilepsia 02/2011; 52(4):826-36. · 3.96 Impact Factor
• Article: Status epilepticus migrainosus: clinical, electrophysiologic, and imaging characteristics.

  Piero Perucca, Michele Terzaghi, Raffaele Manni
  Neurology 07/2010; 75(4):373-4. · 8.31 Impact Factor
• Source

  Available from: actaneurologica.be

  Article: Broad screening for human herpesviridae DNA in multiple sclerosis cerebrospinal fluid and serum.

  Diego Franciotta, Arabella Bestetti, Serena Sala, Piero Perucca, Sven Jarius, Richard W Price, Anna Luisa Di Stefano, Paola Cinque
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  ABSTRACT: Members of the human herpesviridae family are candidates for representing the macroenvironmental factors associated with multiple sclerosis (MS) pathogenesis. Real-time PCR was used to search for DNA of herpes simplex virus type-1/-2, varicella-zoster virus, cytomegalovirus, Epstein-Barr virus (EBV), human herpesvirus 6 type A/B in paired cerebrospinal fluid (CSF) and serum samples from 54 patients with MS, 34 of whom with active disease, 10 patients with other non-infectious neurological diseases, and 15 healthy individuals. All the CSF and serum samples were negative for the examined herpesviruses DNA, except one CSF sample from an MS patient, which was positive for EBV DNA. These findings do not support a role for the here-studied herpesviruses replication, whether in systemic or in the intrathecal compartment, as co-pathogenetic factors, nor as inducers of relapses, in MS.
  Acta neurologica Belgica 12/2009; 109(4):277-82. · 0.54 Impact Factor
• Article: Migralepsy: a call for a revision of the definition.

  Grazia Sances, Elena Guaschino, Piero Perucca, Marta Allena, Natascia Ghiotto, Raffaele Manni
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  ABSTRACT: Migralepsy is an ill-defined nosologic entity, with only a few cases described in the literature. In the 2004 International Classification for Headache Disorders (ICHD-II), the International Headache Society proposed that the following diagnostic criteria should be met: (1) migraine fulfilling criteria for 1.2 Migraine with aura (MA) and (2) a seizure fulfilling diagnostic criteria for one type of epileptic attack occurs during or within 1 h after a migraine aura. Herein, by presenting a case with symptoms suggestive of migralepsy and by reviewing all previous cases described in the literature, we discuss the challenges of differentiating this condition from epileptic seizures, as well as the inaccuracy of the current ICHD-II definition.
  Epilepsia 09/2009; 50(11):2487-96. · 3.96 Impact Factor
• Article: Seizure frequency and sex steroids in women with partial epilepsy on antiepileptic therapy.

  Giovanni Murialdo, Flavia Magri, Gianluca Tamagno, Pietro Ameri, Antonella Camera, Silvia Colnaghi, Piero Perucca, Giambattista Ravera, Carlo Andrea Galimberti
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  ABSTRACT: Neuroactive sex steroids influence neuron excitability, which is enhanced by estradiol (E2) and decreased by progesterone (Pg). In epilepsy, the production, metabolism, biologic availability, and activity of sex hormones may be affected by seizures themselves or by antiepileptic drugs (AEDs). This cross-sectional observational study was aimed at evaluating the relationships between sex steroids, seizure frequency, and other clinical parameters in women with partial epilepsy (PE) on AED treatments. Serum E2, Pg, sex hormone binding globulin (SHBG) levels, free E2 (fE2), and E2/Pg ratios were determined during the follicular and luteal phases in 72 adult women with PE, and in 30 healthy controls. Hormonal data were correlated with seizure frequency, age, body weight, body mass index (BMI), disease onset and duration, and AED therapies. In patients, E2, fE2, and Pg levels were lower in both ovarian phases, whereas those of SHBG were higher than in controls. No significant changes in hormone levels and in prevalence of anovulatory cycles were observed between patients grouped according to their seizure frequency. However, when compared with those in healthy controls, luteal fE2 and Pg levels were chiefly impaired in women with more frequent seizures, mostly undergoing AED polytherapies, but not in those with absent or rarer seizures. The actual changes in sex steroid levels and E2/Pg ratios did not explain an increased seizure frequency in adult women with AED-treated PE, but patients with more severe disease showed more relevant changes in their sex hormone profile and impaired Pg levels during the luteal phase.
  Epilepsia 07/2009; 50(8):1920-6. · 3.96 Impact Factor
• Article: Epilepsy treatment as a predeterminant of psychosocial ill health.

  Piero Perucca, Frank G Gilliam, Bettina Schmitz
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  ABSTRACT: Epilepsy is a chronic disorder with complex effects on social, vocational, physical, and psychological well-being. Patient-oriented research has demonstrated that recurrent seizures have a strong adverse effect on health-related quality of life, but also that seizure rate in persons with pharmacoresistant epilepsy has only a modest correlation with quality of life. Although treatment side effects have received limited attention in epilepsy research, available evidence indicates that adverse medication effects may explain more variance in quality of life than any other clinical variable in persons with pharmacoresistant epilepsy. Furthermore, systematic screening for adverse effects has been shown to be associated with significant reduction in subjective toxicity and improvement in quality of life. There has been only limited research on the relative contribution of specific adverse effects to impaired health-related quality of life. The relative importance of reduction of medication burden after resective epilepsy surgery or vagal nerve stimulation has similarly received sparse attention. Existing deficiencies in the available published research present challenges and opportunities to perform further investigations to define and improve best clinical practices in epilepsy care.
  Epilepsy & Behavior 05/2009; 15 Suppl 1:S46-50. · 2.34 Impact Factor
• Article: Adverse antiepileptic drug effects: toward a clinically and neurobiologically relevant taxonomy.

  Piero Perucca, Jewell Carter, Victoria Vahle, Frank G Gilliam
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  ABSTRACT: Adverse effects (AEs) of antiepileptic drugs (AEDs) are a major impediment to optimal dosing for seizure control. Better understanding of clinical properties of AEs is a prerequisite for systematic research of their neurobiological underpinnings. This study aimed to define specific patterns of AE occurrence and determine their clinical relevance based on their association with subjective health status. Two hundred subjects with epilepsy completed validated self-report health assessments, including the Adverse Event Profile (AEP) and Quality of Life in Epilepsy Inventory (QOLIE)-89. Factor analysis was performed on the 19 AEP items to identify distinct classes of AEs. Correlations between AE class scores and QOLIE-89 scores were evaluated. Multivariate analysis was used to assess contributions of AE class scores to QOLIE-89 scores after controlling for depression and seizure frequency. Relationships between changes in AE class scores and changes in QOLIE-89 scores were also investigated in a subgroup of 62 subjects enrolled in a randomized trial. The mean number of AEs per subject was 6.5. AEs were segregated into five classes: Cognition/Coordination, Mood/Emotion, Sleep, Weight/Cephalgia, and Tegument/Mucosa. Higher scores in each AE class were associated with lower QOLIE-89 scores. Cognition/Coordination scores were the strongest predictor of QOLIE-89 scores. Improvements in Cognition/Coordination, Mood/Emotion, and Tegument/Mucosa scores were associated with improvements in QOLIE-89 scores. Improved Cognition/Coordination was the only predictor of improved QOLIE-89. Adverse effects (AEs) of antiepileptic drugs can be classified in five biologically plausible factors. When specific classes of AEs are identified and attempts are made to reduce them, quality of life is significantly improved.
  Neurology 05/2009; 72(14):1223-9. · 8.31 Impact Factor
• Article: Changes in sex steroid levels in women with epilepsy on treatment: relationship with antiepileptic therapies and seizure frequency.

  Carlo Andrea Galimberti, Flavia Magri, Francesco Copello, Carla Arbasino, Spyridon Chytiris, Massimo Casu, Pietro Ameri, Piero Perucca, Giovanni Murialdo
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  ABSTRACT: Reproductive dysfunction in epilepsy is attributed to the seizures themselves and also to antiepileptic drugs (AEDs), which affect steroid production, binding, and metabolism. In turn, neuroactive steroids may influence neuronal excitability. A previous study in this cohort of consecutive women with epilepsy showed that patients with more frequent seizures had higher cortisol and lower dehydroepiandrosterone sulfate levels than those with rare or absent seizures. The present study was aimed at evaluating, in these same women, the possible relationship between some clinical parameters, seizure frequency, AED therapies, and sex hormone levels. Estradiol (E2), progesterone (Pg), sex hormone-binding globulin (SHBG), and free estrogen index (FEI) were measured during the luteal phase in 113 consecutive females, 16-47 years old, with different epilepsy syndromes on enzyme-inducing AED (EIAED) and/or non-enzyme-inducing AED (NEIAED) treatments, and in 30 age-matched healthy women. Hormonal data were correlated with clinical parameters (age, epilepsy syndrome, disease onset, and duration), seizure frequency assessed on the basis of a seizure frequency score (SFS), and AED therapies. E2, Pg, and FEI were lower, whereas SHBG levels were higher in the epilepsy patients than in the controls. However, sex steroid and SHBG levels were not different between groups of patients categorized according to SFS. Therapies with EIAEDs accounted for changes in E2 levels and FEI. Despite globally decreased sex steroid levels in serum, actual hormone titers were not significantly correlated with SFS in consecutive epilepsy women; rather, these hormonal changes were explained by AED treatments, mainly when EIAED polytherapies were given.
  Epilepsia 02/2009; 50 Suppl 1:28-32. · 3.96 Impact Factor