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Biomedical subjects

Raj D Sheth

Publications and source records attributed to Raj D Sheth.

17 recordsLinked to original sources
PubMed2006

Pathological fractures in epilepsy.

Fracture rates in epilepsy are two to three times that for the general population, although the influence of gender and age is not well defined. We examined, over a 7-year period at a single health care center, 750 patients with epilepsy who sustained the fractures. Among these patients, 293 (39%) had pathological fractures and 457 (61%) had traumatic/seizure-related fractures. Pathological fractures accounted for 71% of the 146 patients >60 years, a group traditionally at risk for pathological fractures (P<0.02). Fractures in epilepsy are distributed with bimodal peaks in the fifth and eighth decades of life, although pathological fractures are a significant contributor across the life span, accounting for 20 to 40% of patients traditionally thought not to be at risk for involutional osteoporotic fractures. Together these findings suggest that epilepsy, and/or its treatment, is a dominant influence in the pathogenesis of fractures and may exacerbate the effects of aging-related involutional osteoporosis.

Adolescent↗
PubMed2006

Protracted ictal confusion in elderly patients.

BACKGROUND: Ictal confusion, particularly if protracted, often presents a diagnostic challenge. OBJECTIVES: To define protracted ictal confusion in elderly patients and to characterize its features and outcome. DESIGN: Case series. SETTING: Neurology outpatient and emergency departments at 2 tertiary care centers. PATIENTS: Consecutive series of 22 ambulatory patients with acute ictal confusion. MAIN OUTCOME MEASURES: Duration of ictal confusion was correlated with age and lesions noted on cerebral images and videoelectroencephalographic studies. RESULTS: The ictal basis underlying confusion was not recognized for up to 5 days in 22 patients (mean +/- SD age, 70 +/- 8.5 years). Twenty patients had partial complex status epilepticus, and 2 patients had newly diagnosed primary generalized status epilepticus. Motor movements were not present in either group, although reduced mood states and ictal neglect were noted in some patients. Fifteen patients had previous episodes (2-10) of protracted ictal confusion. Once identified, treatment reversed confusion, and eventually patients were discharged to home, although a few patients sustained persistent reduction in baseline cognition. CONCLUSIONS: Protracted ictal confusion is often not considered in the ambulatory elderly patient, with resulting delay in diagnosis. Electroencephalographic and videoelectroencephalographic studies performed while the patient is experiencing symptoms are crucial to early diagnosis and timely management.

Age Factors↗
PubMed2006

Optimizing epilepsy management in teenagers.

Optimal epilepsy management in teenage patients represents a particular challenge. These patients are often likely to respond more positively to a regimen that least disrupts their activities. In addition, as a patient group, they are more sensitive to peer perception. Current perceptions of older antiepilepsy drugs do not take into account frequent undesirable side effects or potential adverse interactions with other drugs. Furthermore, they often do not completely control seizures. Recent data suggest that not only do the newer antiepileptic drugs appear to be as efficacious as the older drugs, they also often have more favorable cognitive, cosmetic, and teratogenic side-effect profiles. In addition, newer antiepileptic drugs are being used more often in monotherapy. Successful management of epilepsy in teenagers requires that physicians not only understand the advantages that the newer antiepileptic drugs appear to provide but also consider the social impact of treatment on their patients.

Adolescent↗
PubMed2005

Oral absorption kinetics of levetiracetam: the effect of mixing with food or enteral nutrition formulas.

BACKGROUND: Levetiracetam (LEV) is an antiepileptic drug with a favorable pharmacokinetic profile, including negligible protein binding and linear elimination kinetics. Because LEV is likely to be used in populations that include children and the elderly, alternative techniques of administration, such as crushing the tablet and mixing its contents with semisolid food or enteral nutrition formulas (ENFs), may be required in some clinical settings. Although previous studies have suggested that administration with food does not affect the overall absorption of LEV, there is a lack of data regarding concomitant administration with ENFs. OBJECTIVE: The objective of this study was to evaluate the oral absorption of LEV after concomitant administration with food or ENFs. METHODS: This was an unblinded, 3-way crossover study. After an overnight fast, subjects received a single dose of LEV 500 mg administered either as an intact tablet with 120 mL water (control, treatment A) or crushed and mixed with 4 oz applesauce (treatment B) or 120 mL of a common ENF (treatment C). All subjects received each treatment in a randomized sequence; there was a 7-day washout period between treatments. Serial blood samples were obtained over 24 hours for determination of the LEV serum concentration-time profile using gas chromatography with nitrogen phosphorus detection. AUC(0-24), C(max), and T(max) were calculated using noncompartmental methods and analyzed using analysis of variance. RESULTS: Ten healthy adult volunteers (6 men, 4 women) participated in the study (mean [SD] age, 28.9 [6.5] years; mean body weight, 78.6 [12.9] kg). No significant differences were noted between control and any other study treatment. Mean AUC values were 191.9 (50.2), 165.7 (43.4), and 168.3 (43.9) microg/mL . h for treatments A, B, and C, respectively. Mean T(max) values were 1.08 (0.65), 1.32 (0.75), and 1.62 (0.73) hours, respectively. Mean C(max) values were 14.8 (5.6), 12.1 (2.8), and 10.8 (2.0) microg/mL for the respective treatments. Mean LEV serum concentrations at 12 hours after dosing were similar for all study treatments (3.9, 4.1, and 4.0 microg/mL). The long-term stability of LEV in the various combinations was not assessed. CONCLUSIONS: In these healthy volunteers, the overall rate and extent of absorption of oral LEV were not significantly impaired after crushing and mixing of the tablet with either a food vehicle or a typical ENF product. The data suggest that peak serum concentrations of LEV may be slightly reduced after mixing with ENFs, although the difference was not significant compared with control values.

Administration, Oral↗
PubMed2005

Nonpharmacological treatment options for epilepsy.

Approximately one third of children with epilepsy have persistent seizures despite trials of multiple antiepileptic medications. For some of these patients, epilepsy surgery may provide freedom from seizures. However, in many cases, epilepsy surgery is not a viable treatment option. Nonpharmacological approaches are a useful adjunct to help manage seizures in these children. This review examines the role of vagus nerve stimulation, the ketogenic diet, and various forms of EEG biofeedback therapy in children with intractable epilepsy. Although the mechanism of action is not known precisely for any of these adjunctive therapies, they add an important and evolving dimension to the management of difficult to control epilepsy in children. In addition, pyridoxine-dependent seizures are discussed as an example of an etiology of refractory seizures that responds well to replacement therapy.

Allylamine↗
PubMed2005

Sleep architecture in children with idiopathic generalized epilepsy.

PURPOSE: Children with epilepsy experience sleep disturbances, behavioral and attentional problems at higher rates than their peers. However, the relation between sleep disturbances and the observed behavioral and attentional abnormalities is poorly defined. METHODS: Children with primary generalized epilepsy who were seizure free and between the ages of 5 and 18 years were matched with age- and gender-matched healthy controls and underwent two consecutive nights of nocturnal polysomnography with extended electroencephalography. Connor's Continuous Performance Test (CPT) was administered to assess daytime attentional function. Parents completed the Child Behavior Checklist (CBCL) to assess their emotional-behavioral status. Two sample t tests were used to examine group differences. Spearman correlations were used to examine the relation between sleep variables and behavior and attention variables. Multiple regression analysis was used to identify independent predictors of abnormal behavior and attention among patients. RESULTS: Eleven children with primary generalized epilepsy and eight age- and sex-matched controls participated in the study. Children with epilepsy had longer stage 1 sleep percentage (7.19 +/- 3.2 vs. 4.8 +/- 3.5; p = 0.05) and latency to rapid-eye-movement (REM) sleep (123.5 +/- 40.1 vs. 101.75 +/- 24.3; p = 0.018) compared with controls. Children with epilepsy had worse attention (CPT index, 10.94 +/- 6.55 vs. 3.42 +/- 4.04; p = 0.004) and exhibited significantly higher CBCL Total Behavior and Internalizing Behavior Problem scales. Whereas regression analysis showed no independent predictors of abnormal behavior and attention, a tendency toward association between CBCL total behavior scale and REM percentage (r= 0.55; p = 0.07), and between CPT overall index and stage 1 sleep percentage (r= 0.40; p = 0.10) was noted. CONCLUSIONS: Sleep architecture is abnormal in children with primary generalized epilepsy. Further studies are needed to determine whether abnormalities in sleep architecture contribute to poor daytime behavior and attention.

Adolescent↗
PubMed2004

Metabolic concerns associated with antiepileptic medications.

Because treatment with antiepileptic drugs (AEDs) is often for years or lifelong, physicians should be aware of the metabolic changes that can be associated with AED use and the potential effects of these changes during long-term therapy. Alterations of bone metabolism leading to decreased bone mineral density, associated particularly but not exclusively with the hepatic enzyme-inducing AEDs, can worsen the risk for fractures, which is already increased in patients with epilepsy by factors such as seizure-related falls and trauma. Some AEDs are associated with weight gain, an effect that is not only distressing to many patients but may be sufficient to increase the risk for cardiovascular disease and other disorders associated with excessive body weight. The carbonic anhydrase-inhibiting properties of some AEDs can lead to metabolic acidosis. The AEDs that inhibit carbonic anhydrase are also associated with an increase in risk for renal stones, as is the ketogenic diet. Awareness of the potential metabolic disturbances associated with AED use is particularly important because many of them are subtle and may take years to become clinically apparent.

Acidosis↗
PubMed2004

Bone health in pediatric epilepsy.

Childhood and adolescence are critical periods of skeletal mineralization. Peak bone mineral density achieved by the end of adolescence determines the risk for later pathological fractures and osteoporosis. Chronic disease and medication often adversely affect bone health. Epilepsy is one of the most common neurological conditions occurring in persons under the age of 21. Epilepsy may affect bone in a number of ways. Restrictions of physical activity imposed by seizures; limitations on physical activity resulting from cerebral palsy, frequently present in patients with symptomatic epilepsy; and medications used to treat seizures can all adversely affect bone health. It has long been observed that treatment with phenytoin and phenobarbital can be associated with rickets. More recently, established agents such as carbamazepine and valproate have been shown to be associated with a lowering of bone mineral density. The literature related to bone health in pediatric epilepsy is reviewed, although it should be noted that these data are limited.

Adolescent↗
PubMed2003

Levetiracetam does not alter body weight: analysis of randomized, controlled clinical trials.

INTRODUCTION: Increases in body weight gain are important, and clinically significant adverse effects of several antiepileptic drugs (AED) including valproate and gabapentin. Weight gain may contribute to medication non-compliance, discontinuation, and importantly, may have secondary medical implications as well. Levetiracetam (LEV) is indicated for adjunctive treatment of partial seizures. The objective of the present evaluation was to examine the effects of LEV treatment on body weight in adult patients. METHODS: We analyzed data derived from four prospective, placebo-controlled randomized, clinical trials conducted in both in the US and Europe. Patients included in the present analysis were both men and women, greater than 16 years old, and who had LEV exposure for at least 1 month. Body weight was measured at baseline and at the final LEV study visit. Data are analyzed for all patients, by gender, body mass index (BMI), duration of LEV exposure and by concomitant AED treatment. Wilcoxan Signed Rank, or Rank Sum test used where appropriate, with significance assigned at P<0.05. Data are presented as mean values+/-1 S.D. RESULTS: Nine-hundred and seventy patients (age=37.5 years, 54% men/46% women) were evaluated. There were no significant differences in baseline demographics between LEV (n=631) or placebo (n=339) treated patient groups. Mean LEV dose and duration of treatment were 2053 mg/day (maximum dose of 4000 mg/day) and 125 days (maximum=181 days), respectively. Concomitant AED therapy included CBZ, PHT, VPA, PB, GBP, LTG, and VGB. For LEV-treated patients, no significant changes in body weight were noted. Mean body weight at baseline versus final study visit for LEV was 74.3+/-16.6 kg and 74.3+/-16.6 kg, respectively. For placebo-treated patients, baseline versus end of treatment weight was 72.4+/-15.4 kg and 72.7+/-15.9 kg, respectively, representing a slight, yet clinically trivial increase. Clinically significant weight change as defined as >7% change from baseline weight, occurred in 9% of LEV-treated patients (4.5% had increase in weight/4.5% decrease) versus 9.4% (5.9% had increase/3.5% decrease) in placebo-treated patients. Weight changes were not significantly different between groups. Neither baseline BMI, gender, or background AEDs, appeared to predispose to significant weight change for LEV-treated patients. CONCLUSIONS: We conclude that treatment with LEV at clinically relevant dosages is not associated with significant weight change. LEV would, therefore, appear to be a weight neutral AED.

Adult↗
PubMed2003

Extratemporal quantitative MR volumetrics and neuropsychological status in temporal lobe epilepsy.

Neuropsychological studies of temporal lobe epilepsy have focused heavily on the nature and extent of memory dysfunction and its relationship to the neuropathological status of the hippocampus and related mesial temporal lobe structures. In this study, we examined whole brain and lobar quantitative MRI volumes and comprehensive neuropsychological performance in 58 patients with temporal lobe epilepsy and 62 healthy controls in order to determine (1) the nature and degree of extratemporal structural abnormalities in localization-related temporal lobe epilepsy: (2) the nature and degree of cognitive abnormalities outside of anterograde memory function; and (3) the relationship of volumetric abnormalities to neuropsychological status. Temporal lobe epilepsy patients exhibited significant reduction in the volume of adjusted (age, gender, height) total cerebral tissue (-5.8%), more evident in white (-9.8%) compared to gray matter (-3.0%) tissue volumes. Significant volumetric reductions were evident across frontal, temporal and parietal but not occipital lobe regions. Subarachnoid but not total ventricular CSF was significantly increased in epilepsy patients. Neuropsychological abnormality was generalized in nature, consistent with the generalized nature of the morphometric abnormalities, and reductions in cerebral tissue volumes were directly associated with poorer cognitive performance. In summary, patients with temporal lobe epilepsy exhibited clinically significant structural and functional abnormalities that extended outside the epileptogenic temporal lobe. The degree to which these structural and cognitive abnormalities are due to factors that cause the epilepsy, as opposed to reflecting the consequences of chronic epilepsy (e.g., duration and severity of epilepsy), remain to be determined.

Adolescent↗
PubMed2002

Epilepsy surgery. Presurgical evaluation.

The presurgical evaluation should result in a clear understanding of whether surgery can be undertaken and its associated risks and potential for benefit. The results of surgery are best when there is congruence in the seizure semiology, the irritative zone on interictal EEG, and the ictal onset zone with the epileptogenic lesion as defined on MRI and PET, and when there is a clear understanding of the ictal onset zone's relationship to eloquent cortex as defined by neuropsychologic evaluation, the intracarotid amobarbital test, and cortical functional mapping.

Brain↗
PubMed2002

Intractable pediatric epilepsy: vagal nerve stimulation and the ketogenic diet.

The KD has been proven an effective alternative epilepsy treatment in children refractory to standard anticonvulsants. Children to be placed on the diet must be carefully selected, monitored, and followed. The diet is to be regarded as a strict medical regimen and requires a comprehensive medical team approach in concert with intensive parental involvement. With better understanding of the scientific principles underlying brain ketosis, we should be able to optimize the KD to achieve even better results.

Brain↗
PubMed2002

Adolescent issues in epilepsy.

Approximately one third of new cases of epilepsy have their onset before age 20 years. Many children will enter adolescence with epilepsy or have an onset of seizures during adolescence. Adolescence is a time of dramatic change in growth, hormonal, psychologic, and social situations. Seizure frequency, teenage pregnancy, driving, and alcohol and drug use often become major issues during the adolescent years. Furthermore, adolescents often have difficulty accepting the chronicity of epilepsy and complying with medications, which can result in physical injury and perceived or real obstacles to employment, thereby contributing to low morale. Both pediatricians and neurologists should be aware of adolescent issues in epilepsy.

Adaptation, Psychological↗