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Biomedical subjects

S Arroyo

Publications and source records attributed to S Arroyo.

At least 19 recordsLinked to original sources
PubMed2005

A randomised open-label study of tiagabine given two or three times daily in refractory epilepsy.

Efficacy and tolerability of tiagabine was evaluated in patients with non-controlled partial seizures in a multicentre, open-label, parallel group study. Tiagabine was administered either two (b.i.d.) or three times daily (t.i.d.) as adjunctive therapy and titrated stepwise to a target of 40 mg/day during a 12-week, fixed-schedule titration period; this was followed by a 12-week flexible continuation period. The primary efficacy endpoint was the proportion of patients completing the fixed-schedule titration period. A total of 243 patients were randomised and received treatment, 123 to b.i.d. and 120 to t.i.d. dosing. Fewer patients in the b.i.d. (76 and 62%) than in the t.i.d. (87 and 72%) group completed the fixed-schedule titration period (OR: 0.562; 95% CI: 0.309-1.008; P=0.0532). The median percentage decrease in all types of seizure (excluding status epilepticus) during the fixed schedule titration period was 33.4% for the b.i.d. and 23.8% for the t.i.d. groups (P=0.9634; Van Elteren's test). The proportion of responders was similar for the b.i.d. and t.i.d. groups. There were no significant differences between dosage regimens in the change in median seizure rates from baseline. Adverse events were more frequent during the titration than the continuation period. Most events were mild and related to the central nervous system. Although their incidence was similar between treatment groups, severity was more frequent in the b.i.d. group. Our results suggest that during titration tiagabine is better tolerated with t.i.d. dosing, but during long-term maintenance, a t.i.d. schedule is as effective and well tolerated as b.i.d.

Anticonvulsants↗
PubMed2005

Randomized dose-controlled study of topiramate as first-line therapy in epilepsy.

OBJECTIVES: To evaluate the efficacy and tolerability of topiramate as monotherapy, using a dose-controlled study design. MATERIALS AND METHODS: We conducted a multinational, randomized, double-blind trial in adults and children (> or =6 years old) with epilepsy that was not being treated when randomized to 400 or 50 mg/day topiramate as target maintenance dosages. In addition to > or =2 lifetime unprovoked seizures, patients had to have one or two partial-onset seizures or generalized-onset tonic-clonic seizures in the 3-month retrospective baseline. The primary efficacy end point was time to first seizure; a secondary efficacy measure was the seizure-free rate at 6 months and 1 year. Double-blind treatment continued until 6 months after the last patient was randomized. RESULTS: Kaplan-Meier survival analyses for time to first seizure (intent-to-treat, n = 470) favored 400 mg/day over 50 mg/day (P = 0.0002) as a target maintenance dosage. The first evaluation point with a significant difference (P = 0.046) favoring the higher dose was at day 14 when patients were receiving 100 or 25 mg/day. The probability of being seizure-free at 6 months was 83% in patients randomized to 400 mg/day and 71% in those randomized to 50 mg/day (P = 0.005). Seizure-free rates at 12 months were 76% and 59%, respectively (P = 0.001). Differences favoring the higher dose were significant in patients with partial-onset seizures (P = 0.009) and in those with generalized-onset tonic-clonic seizures (P = 0.005). The most common dose-related adverse events were paresthesia, weight loss, and decreased appetite. Discontinuations due to cognitive-related adverse events were 2% in the 50-mg group and 7% in the 400-mg group. Overall, 7% and 19%, respectively, discontinued with adverse events during the median treatment duration of 9 months. CONCLUSION: Topiramate is effective as monotherapy in adults and children. Because a therapeutic effect emerges during titration, clinicians should adjust dosages in step-wise fashion with intermediate stopping points, e.g., 100 mg/day, to evaluate patient response and achieve the optimal maintenance dosage.

Adolescent↗
PubMed2004

Phenotype characterization and natural history of spondylothoracic dysplasia syndrome: a series of 27 new cases.

Spondylothoracic dysplasia (STD, MIM#277300) is an autosomal recessive disorder with high prevalence in the Puerto Rican population. It is generally regarded as a lethal condition. Since Jarcho and Levin described it in 1938, it has been referred to as spondylocostal dysplasia, costovertebral dysplasia, Jarcho-Levin syndrome and STD. We have prospectively characterized 27 patients with STD by detailed physical examination, pedigree analysis, thoracic CT scans, and pulmonary function tests (PFTs). Diagnoses were established using spinal radiographs and 3-D reconstructive CT scans to demonstrate fusion of the ribs at the costo-vertebral junction with a fan-like (crab-like) configuration of the thorax. Vertebral segmentation and formation defects were seen throughout the spine with a decrease in the number of vertebral bodies. Characteristic vertebral shape consisted of a decrease in antero-posterior diameter and an increase in lateral length, giving the vertebra a sickle shape. Eight out of 18 prospectively follow patients died within the first 6 months of life, a 44% mortality rate. Cause of death was respiratory insufficiency secondary to pneumonia and pulmonary restriction. This is an important finding since the vast majority of STD syndrome patients cited in the medical literature have died in the newborn and early childhood periods. Age of the remaining patients ranged from 4 months to 47 years. This represents the largest collection of patients with STD reported and it has allowed us to determine a detailed phenotype. Given 56% survival at 6 months, we show that STD is not a lethal syndrome.

Abnormalities, Multiple↗
PubMed2004

Can the Wada test evaluate mesial temporal function? A SPECT study.

OBJECTIVE: To assess the value of SPECT during intracarotid amobarbital procedure (IAP) to discriminate which patients performed the test with the hippocampus inactivated and correlate it with the risk of amnesia after anterior temporal lobectomy (ATL). METHODS: The authors studied 40 consecutive patients undergoing ATL for refractory epilepsy. SPECT was performed after IV injection of 99mTc-HMPAO during the IAP (IAP-SPECT). Interictal SPECT and IAP-SPECT were realigned to obtain the perfusion change percentage (PCP), allowing a quantitative measurement. Wechsler Memory Scale Revised (WMS-R) before and during the first year of follow-up was used to assess memory impairment after surgery. RESULTS: A decrease between 10 and 12% of the mean PCP values was observed in the frontal, parietal, and lateral temporal lobes of the injected side and in the contralateral cerebellum. However, no significant PCP changes were observed in the occipital or mesial temporal lobes. Thirty-eight passed the memory evaluation of the IAP and in 6 of those 38 patients a decline in memory was demonstrated 1 year after ATL. However, high preoperative neuropsychological score (in two patients) and IAP asymmetry scores (in other three patients) predicted postoperative memory risk in five of these six patients. Fourteen of the 38 patients (40%) had hypoperfusion of the hippocampus during the IAP-SPECT (i.e., the hippocampus was inactivated) and only 1 of these 14 patients (2.5%) developed memory impairment after temporal lobectomy. On the other hand, 5 of the 24 patients (13%) who had a functional hippocampus on IAP-SPECT developed memory impairment. CONCLUSIONS: The results suggest that the combination of SPECT, intracarotid amobarbital procedure, and neuropsychological testing predicted risk for all patients who had postoperative memory decline, indicating that risk prediction should be based on multiple factors. IAP-SPECT results demonstrated that the hippocampus is not inactivated in over 60% of patients and that the lack of accuracy of the IAP alone in predicting the risk of amnesia is probably related to an insufficient inactivation of the ipsilateral hippocampus during the test.

Adolescent↗
PubMed2002

A crossover, add-on trial of talampanel in patients with refractory partial seizures.

The authors report a double-blind, placebo-controlled, crossover study of talampanel in 49 patients with refractory partial seizures. Three doses of talampanel were investigated based on differences in patients' concomitant antiepileptic drug usage. Talampanel showed efficacy in reducing seizure frequency (p = 0.001) with a median seizure reduction of 21%. Eighty percent of patients had fewer seizures on talampanel than on placebo. Dizziness (52%) and ataxia (26%) were the only significant adverse events.

Adult↗
PubMed2001

Nocturnal paroxysmal dystonia related to a prerolandic dysplasia.

Nocturnal paroxysmal dystonia (NPD) is a rare disorder characterized by attacks of short-lived dystonic, tonic and choreoatetoid movements occurring mainly during sleep. Although seizures are believed to arise from the frontal lobe, their localization is, however, uncertain due to the lack of ictal clinical-EEG correlations. Two patients are reported with episodes clinically compatible with NPD who also experienced occasional generalized tonic-clonic seizures in which there was a frontal (prerolandic) dysplasia detected by MRI. In one patient interictal/ictal SPECTs suggested that the seizure focus was over the area of dysplasia. Both patients support the notion that NPD is a type of epilepsy arising from the frontal lobe, possibly originating in the prerolandic region.

Adult↗
PubMed2001

Life-threatening adverse events of antiepileptic drugs.

Treating a patient with antiepileptic drugs (AEDs) may give rise to unexpected life-threatening adverse events. Despite extensive experimental and clinical testing to ensure safety, most AEDs on the market have been associated with cases of severe cutaneous reactions, serious hematological disorders, or hepatic failure. Most of these disorders emerge as idiosyncratic immune-mediated disease or are related to toxic metabolic products of the AEDs. Early diagnosis is the only means of reducing the harmful, potentially fatal effects of these reactions. A high degree of suspicion, knowledge of risk factors, and close physician-patient contact increases the likelihood of early diagnosis and treatment. When diagnosed, severe reactions must be fully documented and reported to health authorities. The very rare occurrence of life threatening events should not, in general, limit treatment decision-making. Future epidemiological, chemical, and genetic research might provide methods for ascertaining which patients are at risk, so undue exposure can be avoided.

Anticonvulsants↗
PubMed2001

Recommendations on the clinical use of oxcarbazepine in the treatment of epilepsy: a consensus view.

Extensive clinical use and a series of clinical trials have shown that oxcarbazepine is a valuable antiepileptic drug for the treatment of adults and children with partial onset seizures both in initial monotherapy, for conversion to monotherapy and as adjunctive therapy. The clinically recommended titration scheme for all forms of therapy in adults is to start with 150 mg/day at night and to increase by 150 mg/day every second day until a target dose of 900-1200 mg/day is reached. If necessary, one can go faster and start with up to 600 mg/day and titrate with weekly increments of up to 600 mg/day. In children, treatment can be initiated with 8-10 mg/kg/day body weight in two to three divided doses. Dosage can be increased by 8-10 mg/kg/day in weekly increments if necessary for seizure control. Hyponatremia (serum sodium <125 mmol/l) can develop gradually during the first months of oxcarbazepine therapy in approximately 3% of patients with a previously normal serum sodium. However, there is no need to measure baseline serum sodium concentrations unless the patient has renal disease, is taking medication which may lower serum sodium levels (such as diuretics, oral contraceptives or nonsteroidal anti-inflammatory drugs) or--in rare cases--has clinical symptoms of hyponatremia. During oxcarbazepine maintenance therapy measurement of serum sodium levels should also be considered if medications known to decrease sodium levels are added or symptoms of hyponatremia develop. Oxcarbazepine does not appear to have any clinically notable effects on other safety parameters such as renal and liver function or haematological test results. In summary, oxcarbazepine is a safe and well tolerated antiepileptic drug for partial epilepsy.

Anticonvulsants↗
PubMed2001

Treating epilepsy in the elderly: safety considerations.

The incidence of epilepsy increases with advancing age. Epilepsy in the elderly has different aetiologies from that in younger populations, cerebrovascular disease being the most common condition associated with seizures. Partial seizures are the predominant seizure type in older patients. A diagnosis of epilepsy in the elderly is based mainly on the history and is frequently delayed. In addition, seizure imitators are especially frequent. In many cases ancillary tests for diagnosis may show normal age-related variants, sometimes making results difficult to interpret. Treating epilepsy in the elderly is problematic due to a number of issues that relate to age and comorbidity. The physical changes associated with increasing age frequently lead to changes in the pharmacokinetics of many anticonvulsants. The treatment of epilepsy in the elderly is also complicated by the existence of other diseases that might affect the metabolism or excretion of anticonvulsants and the presence of concomitant medications that might interact with them. Moreover, specific trials of anticonvulsants in the aged population are scarce. General guidelines for treatment include starting at lower doses, slowing the titration schedule, individualising the choice of anticonvulsant to the characteristics of the patient, avoiding anticonvulsants with important cognitive or sedative adverse effects, and where possible, treating with monotherapy.

Aged↗
PubMed2001

[Oxcarbazepine].

Oxcarbazepine (OXC) is a new antiepileptic drug derived from carbamazepine (CBZ). OXC has shown efficacy in partial and secondarily generalized seizures in children and adults. It is not indicated in myoclonic epilepsies or absences. OXC has a high bioavailability and is 40% protein-bound. Its metabolism is different from that of CBZ. There is no epoxy derivative, but a monohidroxy derivative (MHD) that is responsible from its clinical efficacy. In several clinical trials OXC has demonstrated efficacy in partial seizures both as add-on and in monotherapy. In these trials, OXC has been found to be as efficacious as CBZ, valproic acid or phenytoin, but with fewer adverse events and better tolerability. The most frequent adverse events of OXC are sedation, somnolence, headache, dizziness, and nausea. Most frequently, adverse events are transient and are minimized with dose reduction. OXC has not been associated with severe hematological, renal, or hepatic adverse events. Aymptomatic hyponatremia has been observed in patients undergoing treatment with OXC, most frequently in patients with diseases or medications predisposing to hyponatremia.

Adult↗
PubMed2000

No evidence of linkage to 6p markers in spanish families with juvenile myoclonic epilepsy.

Juvenile myoclonic epilepsy (JME) is a common subtype of hereditary generalized epilepsy with an uncertain pattern of inheritance. Different studies in multiple families have provided evidence for and against linkage of the disease to chromosome 6p. We performed linkage analysis using microsatellite markers from 6p (D6S109, D6S248, D6S291, D6S426, D6S272, D6S466, D6S294, D6S257) and from centromeric 6q region (D6S402) in seven small families of Spanish origin. The highest LOD scores were obtained under an autosomal dominant inheritance model with a penetrance of 70% but a significant positive LOD score (Z>3) was not reached. LOD scores<-2 were obtained at different markers in three of our families. These results support the concept of genetic heterogeneity in the disease.

Adult↗
PubMed2000

Zinc-rich synaptic boutons in human temporal cortex biopsies.

The distribution of zinc-rich synaptic boutons in biopsies of the temporal cortex from epileptic patients who had undergone surgery is described. Unfixed cryostat sections were exposed to H(2)S vapour to precipitate endogenous zinc, which was subsequently shown by silver enhancement. In the temporal cortex, the stain for zinc was arranged in bands: stain was heavy in layers II and VI, moderate-to-heavy in layers I, III and V, and low in layer IV. The white matter was virtually devoid of staining. At the electron microscope level, labelling was found in synaptic boutons that made asymmetric synaptic contacts. Immunohistochemical staining for glutamate receptor subunits GluR2/3 was observed in cell bodies in layers II, III, V and VI, coincident with the layers that showed heavy staining for zinc. Immunostaining for glutamate receptor subunit GluR1 was prominent in non-pyramidal neurons in deep cortical layers. These results support findings in other mammals and indicate that the human neocortex may contain an extensive system of zinc-rich cortico-cortical connections. This system may be altered in pathological conditions.

Biopsy↗
PubMed2000

Reliability and clinical usefulness of the short-forms of the Wechsler memory scale (revised) in patients with epilepsy.

PURPOSE: The Wechsler Memory Scale-R (WMS-R) is often used for the evaluation of patients with epilepsy, but is time consuming. Two shortened forms of the WMS-R have been published in an effort to reduce the time involved in the test. The purpose of this study is to cross-validate these abbreviated forms in patients with epilepsy. METHODS: We assessed 103 consecutive patients with drug-resistant partial epilepsy being treated in our epilepsy unit. The WMS-R was administered to all patients. The reliability of two shortened versions of the WMS-R were evaluated. The appraisal was performed taking into account the side of the epileptogenic region. The statistical analyses were carried out with the Pearson's correlation and with the intraclass correlation coefficient. RESULTS: Both shortened formulas showed good reliability coefficients for predicting the General Memory and Delayed Recall Indices. In the overall accuracy of the predictions by both short forms no significant differences were found among the three study. groups (right, left or bilateral). However, when considering the predictive error only the three-subtest formulas comprising logical memory, verbal paired associates and visual reproduction efficiently predicted performance, regardless of the side of the epileptogenic region. Of the predicted scores in the overall sample, 92 and 97% fell below the standard error of measurement for general and delayed memory index, respectively. Both short forms correctly classified 89-94% of the performances at the average or impaired level. CONCLUSIONS: The short form of the M-MS-R using three subtests (logical memory, verbal paired associates and visual reproduction) is reliable and time-efficient for estimating the General and Delayed Recall Memory indexes in patients with drug-resistant partial epilepsy.

Adult↗
PubMed2000

Optimized procedure for lamotrigine analysis in serum by high-performance liquid chromatography without interferences from other frequently coadministered anticonvulsants.

The authors have developed a simple isocratic high-pressure liquid chromatographic (HPLC) assay for the simultaneous determination of lamotrigine and other frequently coadministered antiepileptic drugs in serum samples. Lamotrigine extraction was performed on a reversed-phase Oasis HBL preparation column. The eluates containing butalbital as internal standard were separated with a 7-microm Chromsystems C18 250 x 4.0 mm I.D. reversed-phase column at a temperature of 40 degrees C using a mobile phase consisting of pH 3.8 phosphate-acetonitrile buffer (55:45, v/v), at a flow rate of 0.8 mL/min. Ultraviolet detection was carried out at 210 nm. Measurement of the peak:height ratio allowed quantitative determination of the samples. The method was linear over a concentration range of 0.2 to 20 microg/mL for lamotrigine. Recovery was >90%. Within-day and between-day coefficients of variation ranged from 1.8% to 6.7%. The mean lamotrigine concentration was 8.01 +/- 5.63 microg/mL. After studying sera from 130 patients treated with lamotrigine the authors confirmed that associated antiepileptic therapy affected the serum lamotrigine levels, which were significantly higher in patients under valproic acid treatment.

Adolescent↗
PubMed2000

Does neuroticism influence cognitive self-assessment after epilepsy surgery?

PURPOSE: To examine how cognitive, personality, and seizure outcome variables influence the subjective cognitive functioning of patients with refractory temporal lobe seizures after epilepsy surgery. METHODS: Thirty-three consecutive patients with drug-resistant partial epilepsy who underwent surgical treatment at a tertiary referral university epilepsy center were tested before surgery and 1 year after surgery. Objective cognitive and subjective cognitive functioning tests were used, and personality was assessed. Seizure control was operationalized as a dichotomous variable. RESULTS: A significant inverse relationship was found between neuroticism and subjective cognitive functioning. None of the other pre- and postoperative cognitive and surgery outcome variables were significant predictors of subjective cognitive functioning, even after controlling for the effect of neuroticism. CONCLUSIONS: Subjective and objective memory functioning are independent in patients with epilepsy after surgical treatment. Subjective memory functioning appears to be related not to seizure relief but to neuroticism. These data suggest that psychological factors such as personality traits predisposing to emotional distress should be taken into consideration in the clinical management and counseling of patients undergoing epilepsy surgery.

Adult↗
PubMed2000

Cost minimization analysis of antiepileptic drugs in newly diagnosed epilepsy in 12 European countries.

A recent United Kingdom cost minimization analysis (CMA) of four antiepileptic drugs (AEDs) used to treat newly diagnosed adult epilepsy demonstrated that a new drug, lamotrigine (LTG), incurred higher costs than carbamazepine (CBZ), phenytoin (PHT), and valproate (VPA), whose costs were similar. This analysis took account of each drug's side-effect and tolerability profile. The present analysis investigated the costs of treatment with LTG, CBZ, PHT, and VPA in 12 European countries. Data were derived from published sources and from a panel of locally based experts. When no published data were available, estimates were obtained using expert opinion by a consensus method. These data were incorporated into a treatment pathway model, which considered the treatment of patients during the first 12 months after diagnosis. The primary outcome considered was seizure freedom. Randomized controlled trials demonstrate that the drugs considered are equally effective in terms of their ability to achieve seizure freedom, and thus the most appropriate form of economic evaluation is a CMA. These trials provided data on the incidence of side effects, dosages, and retention rates. The economic perspective taken was that of society as a whole and the analysis was calculated on an "intent-to-treat" basis. Only direct medical costs were considered. In each country considered, LTG was twofold to threefold more expensive than the other drugs considered. A sensitivity analysis demonstrated that varying each of the assumptions (range defined by expert panels) did not significantly alter the results obtained.

Anticonvulsants↗
PubMed1999

Carbamazepine in comparative trials: pharmacokinetic characteristics too often forgotten.

OBJECTIVES: To compare the use of carbamazepine (CBZ) in comparative monotherapy trials with its use in practice. BACKGROUND: CBZ is often the drug of first choice for partial onset seizures and is frequently used as the reference drug in comparative trials with newly developed antiepileptic compounds. There are several issues related to CBZ that may have an impact on the final outcome of these trials. CBZ has nonlinear time-dependent kinetics due to autoinduction, and this may cause adverse reactions on starting treatment; somnolence and rash usually occur in the first weeks and may be related to the dose and titration schedule. Total daily dose or the serum levels of the drug do not correlate with therapeutic efficacy. METHODS: Review of the current literature on the pharmacokinetics properties of CBZ and of comparative trials of new antiepileptic drugs that used CBZ as the reference drug. CONCLUSIONS: The use of CBZ differed in comparative clinical trials and in clinical practice, with slower and lower titration rates used in the latter. This may be disadvantageous for CBZ because its pharmacokinetics peculiarities are ignored. If CBZ is to be used in these trials, titration rates and dosages should resemble those used in clinical practice because this is likely to improve efficacy and tolerability. Otherwise, the results of these trials may support regulatory applications but have little relevance to clinical practice. We suggest an initial CBZ dose of 100 mg/d and a slow titration schedule with dose incremental steps of 100 mg/d every week up to 600 mg/d. Blood levels should determine the initial target dose, but after this has been achieved titration should be based on seizure control and tolerability rather than by blood levels.

Carbamazepine↗