Bio

Clinical Focus


  • Epilepsy
  • Epilepsy Device Therapy
  • Neurology

Academic Appointments


Professional Education


  • Board Certification: Epilepsy, American Board of Psychiatry and Neurology (2013)
  • Residency:University of Pennsylvania School of Medicine (1988) PA
  • Medical Education:Stanford University School of Medicine (1984) CA
  • Fellowship:Graduate Hospital (1990) PA
  • Board Certification: Neurology, American Board of Psychiatry and Neurology (1989)
  • Internship:University of Pennsylvania School of Medicine (1985) PA

Publications

Journal Articles


  • Responsive cortical stimulation for the treatment of medically intractable partial epilepsy NEUROLOGY Morrell, M. J. 2011; 77 (13): 1295-1304

    Abstract

    This multicenter, double-blind, randomized controlled trial assessed the safety and effectiveness of responsive cortical stimulation as an adjunctive therapy for partial onset seizures in adults with medically refractory epilepsy.A total of 191 adults with medically intractable partial epilepsy were implanted with a responsive neurostimulator connected to depth or subdural leads placed at 1 or 2 predetermined seizure foci. The neurostimulator was programmed to detect abnormal electrocorticographic activity. One month after implantation, subjects were randomized 1:1 to receive stimulation in response to detections (treatment) or to receive no stimulation (sham). Efficacy and safety were assessed over a 12-week blinded period and a subsequent 84-week open-label period during which all subjects received responsive stimulation.Seizures were significantly reduced in the treatment (-37.9%, n = 97) compared to the sham group (-17.3%, n = 94; p = 0.012) during the blinded period and there was no difference between the treatment and sham groups in adverse events. During the open-label period, the seizure reduction was sustained in the treatment group and seizures were significantly reduced in the sham group when stimulation began. There were significant improvements in overall quality of life (p < 0.02) and no deterioration in mood or neuropsychological function.Responsive cortical stimulation reduces the frequency of disabling partial seizures, is associated with improvements in quality of life, and is well-tolerated with no mood or cognitive effects. Responsive stimulation may provide another adjunctive treatment option for adults with medically intractable partial seizures. Classification of evidence: This study provides Class I evidence that responsive cortical stimulation is effective in significantly reducing seizure frequency for 12 weeks in adults who have failed 2 or more antiepileptic medication trials, 3 or more seizures per month, and 1 or 2 seizure foci.

    View details for DOI 10.1212/WNL.0b013e3182302056

    View details for Web of Science ID 000295253800019

    View details for PubMedID 21917777

  • Normal vitamin D and low free estradiol levels in women on enzyme-inducing antiepileptic drugs EPILEPSY & BEHAVIOR Pack, A. M., Morrell, M. J., McMahon, D. J., Shane, E. 2011; 21 (4): 453-458

    Abstract

    Relationships between reproductive hormone levels, bone turnover marker levels, bone mineral density, and rates of bone loss were evaluated in premenopausal women with epilepsy taking enzyme-inducing antiepileptic drugs (EIAEDs: phenytoin or carbamazepine) or lamotrigine. Calciotropic and reproductive hormone levels, bone turnover marker levels, and bone mineral density were measured at baseline and 1 year. Bone mineral density did not differ between groups. Serum calcium (P<0.001) and estrone (P<0.001) levels were lower in the EIAED group. Sex hormone-binding globulin levels were higher (P<0.001) and percentage free estradiol levels were lower (P<0.001) in the EIAED group. We detected no relationship between bone mineral density change and calciotropic hormone or bone turnover marker levels. Women with higher sex hormone-binding globulin and lower free estradiol levels sustained more bone loss at the total hip (P=0.04 and P=0.02) and a trend toward more bone loss at the lumbar spine (P=0.07 and P=0.08). These findings suggest that lower estrogen levels may contribute to bone loss in premenopausal women with epilepsy.

    View details for DOI 10.1016/j.yebeh.2011.05.001

    View details for Web of Science ID 000294104900024

    View details for PubMedID 21704565

  • Intracranial Stimulation Therapy for Epilepsy NEUROTHERAPEUTICS Skarpaas, T. L., Morrell, M. J. 2009; 6 (2): 238-243

    Abstract

    Epilepsy is a common chronic neurological disorder effecting 1 to 2% of the population. Despite advances in anti-epileptic drug therapy, epilepsy surgery, and vagus nerve stimulation, approximately 30% of patients continue to have seizures. Intracranial stimulation is currently under investigation as an adjunctive treatment to anti-epileptic medications in adults with medically intractable epilepsy. Several different approaches are now being investigated. Specifically, acute and long-term clinical studies have delivered stimulation either to inhibitory regions outside the seizure focus or directly to the seizure focus. These studies have demonstrated the safety of intracranial stimulation and proof of principle in epilepsy patients. In addition to the different locations tested, clinical studies have also used different temporal patterns of stimulation. The majority of studies have used open-loop or scheduled stimulation, in which, stimulation is delivered on a fixed schedule and is independent of electrographic activity. In contrast, a number of recent investigations have demonstrated the feasibility of closed-loop or responsive stimulation, which is stimulation that is contingent upon the detection of epileptiform activity. This chapter will review the acute and long-term clinical studies of intracranial stimulation, including focal, and nonfocal, and open-loop and responsive stimulation. We will also discuss the optimization and safety of therapeutic parameters used in neurostimulation for epilepsy.

    View details for Web of Science ID 000264659900004

    View details for PubMedID 19332315

  • Hyperandrogenism, ovulatory dysfunction, and polycystic ovary syndrome with valproate versus lamotrigine ANNALS OF NEUROLOGY Morrell, M. J., Hayes, F. J., Sluss, P. M., Adams, J. M., Bhatt, M., Ozkara, C., Warnock, C. R., Isojarvi, J. 2008; 64 (2): 200-211

    Abstract

    To evaluate development of components of polycystic ovary syndrome (PCOS) and PCOS in women with epilepsy initiating valproate or lamotrigine therapy.Female individuals with epilepsy and regular menstrual cycles were eligible for this prospective study. Participants were randomized to 12 months of valproate (n = 225) or lamotrigine (n = 222) therapy. Serum androgen levels were measured every 3 months. Urinary pregnanediol glucuronide levels were measured weekly for two 3-month periods. The primary end point was development of PCOS components (ie, hyperandrogenism or ovulatory dysfunction). A post hoc analysis was conducted in women more than 2 years after menarche (177 lamotrigine, (HA) 186 valproate) to exclude OD the confounding effect of puberty.More women in the valproate group than the lamotrigine group developed (OD) in the prospective (54% valproate, 38% lamotrigine; p = 0.010) and the post hoc (HA) analyses (36% valproate, 23% lamotrigine; p = 0.007). More women in the valproate group than the lamotrigine group developed PCOS (9 vs 2%; p = 0.007). Development of HA was more frequent with OD valproate than lamotrigine among those initiating treatment at age younger than 26 years (44% valproate, 23% lamotrigine; p = 0.002) but was similar if treatment was started at age 26 years or older (24% valproate, 22% lamotrigine).Development of HA occurred more frequently with valproate than lamotrigine, especially if medication was started at age younger than 26 years.

    View details for DOI 10.1002/ana.21411

    View details for Web of Science ID 000258921800011

    View details for PubMedID 18756476

  • Bone health in young women with epilepsy after one year of antiepileptic drug monotherapy NEUROLOGY Pack, A. M., Morrell, M. J., Randall, A., McMahon, D. J., Shane, E. 2008; 70 (18): 1586-1593

    Abstract

    Antiepileptic drugs (AEDs) may have adverse effects on bone mineral density (BMD) and metabolism. We previously reported biochemical evidence of increased bone turnover in premenopausal women with epilepsy on phenytoin monotherapy compared with those on carbamazepine, lamotrigine, and valproate. We therefore hypothesized that rates of bone loss would be higher in young women treated with phenytoin.Ninety-three premenopausal women with epilepsy receiving a single AED (carbamazepine, lamotrigine, phenytoin, or valproate) participated. Subjects completed nutritional and physical activity questionnaires. Biochemical indices of bone and mineral metabolism and BMD of the proximal femur and lumbar spine were measured at baseline and 1 year.Participants reported high calcium intake (>1,000 mg/day) and were physically active. Significant loss (2.6%) was seen at the femoral neck in the phenytoin group. BMD remained stable in the other AED groups. Bone turnover markers and calciotropic hormones were unchanged after 1 year in all groups except for a significant decline in urine N-telopeptide in the phenytoin group. In women receiving phenytoin, lower serum 25-hydroxyvitamin D concentrations were associated with higher parathyroid hormone, bone alkaline phosphatase, and urine N-telopeptide levels, a biochemical pattern consistent with secondary hyperparathyroidism and increased remodeling.In this study, young women treated with phenytoin had significant femoral neck bone loss over 1 year. In contrast, those treated with carbamazepine, lamotrigine, and valproate did not have detectable adverse effects on bone turnover or bone mineral density. These results raise concerns about the long-term effects of phenytoin monotherapy on bone in young women with epilepsy.

    View details for Web of Science ID 000256706900003

    View details for PubMedID 18443309

  • Responsive cortical stimulation for the treatment of epilepsy NEUROTHERAPEUTICS Sun, F. T., Morrell, M. J., Wharen, R. E. 2008; 5 (1): 68-74

    Abstract

    Epilepsy is a common chronic neurological disorder affecting approximately 1-2% of the population. Despite the available treatment options (pharmacotherapy, surgery, and vagus nerve stimulation), a large percentage of patients continue to have seizures. With the success of deep brain stimulation for treatment of movement disorders, brain stimulation has received renewed attention as a potential treatment option for epilepsy. Responsive stimulation aims to suppress epileptiform activity by delivering stimulation directly in response to electrographic activity. Animal and human data support the concept that responsive stimulation can abort epileptiform activity, and this modality may be a safe and effective treatment option for epilepsy. Responsive stimulation has the advantage of specificity. In contrast to the typically systemic administration of pharmacotherapy, with the concomitant possibility of side effects, electrical stimulation can be targeted to the specific brain regions involved in the seizure. In addition, responsive stimulation provides temporal specificity. Treatment is provided as needed, potentially reducing the likelihood of functional disruption or habituation due to continuous treatment. Here we review current animal and human research in responsive brain stimulation for epilepsy and then discuss the NeuroPace RNS System, an investigational implantable responsive neurostimulator system that is being evaluated in a multicenter, randomized, double-blinded trial to assess the safety and efficacy of responsive stimulation for the treatment of medically refractory epilepsy.

    View details for Web of Science ID 000252532300008

    View details for PubMedID 18164485

  • Treatment of epilepsy in adults: expert opinion, 2005 EPILEPSY & BEHAVIOR Karceski, S., Morrell, M. J., Carpenter, D. 2005; 7: S1-S64

    Abstract

    Over the past decade, there has been a proliferation of new therapies for the treatment of epilepsy. Faced with this growing list of options, clinicians must decide what therapy, or combination of therapies, is best for a given individual. Although controlled clinical trials exist for each treatment option, the answer to these questions may remain unclear. In 2000, a survey of expert opinion was done to address questions concerning which treatment options might be best in a number of clinical situations. We surveyed a group of US epileptologists again in 2004 and compared the results of the two surveys.We sent a questionnaire on the treatment of adolescent and adult epilepsy syndromes to a group of opinion leaders in the field of epilepsy. The questions were formatted to simulate real-world clinical situations in the treatment of symptomatic localization related epilepsy (SLRE) and idiopathic generalized epilepsy (IGE). The experts were asked to rate treatment options based on a modified RAND 9-point scale (with "9" most appropriate and "1" least appropriate). Statistical analysis of data was performed as defined by the expert consensus method. The results were used to develop user-friendly recommendations concerning overall treatment strategies and choice of specific medications.Of the 48 experts to whom the survey was sent, 43 (90%) responded; 29 (67%) of the respondents had also participated in the first survey. For initial monotherapy for IGE (generalized tonic-clonic [GTC], absence, and myoclonic seizures), valproate was rated as treatment of choice. For IGE-GTC seizures, lamotrigine and topiramate were also identified as usually appropriate for initial monotherapy. For IGE-absence seizures, ethosuximide was also a treatment of choice, and lamotrigine was usually appropriate. For SLRE, the experts were again asked to rate treatment options based on seizure type: simple partial seizures (SPS), complex partial seizures (CPS), and secondarily generalized tonic-clonic seizures (SGTC). In SLRE-SPS and SLRE-SGTC, carbamazepine and oxcarbazepine were treatments of choice, with lamotrigine and levetiracetam also usually appropriate. In SLRE-CPS, carbamazepine, lamotrigine. and oxcarbazepine were treatments of choice, while levetiracetam was also usually appropriate. For women who are pregnant or trying to conceive, lamotrigine was treatment of choice for both syndrome types. In the elderly, whether medically stable or ill, the treatment of choice was lamotrigine, while levetiracetam was also usually appropriate (along with gabapentin for persons with comorbid medical illness). In persons with HIV and epilepsy, lamotrigine and levetiracetam were usually appropriate. In people with both epilepsy syndromes who have depression, lamotrigine was treatment of choice. In a person with seizures and renal disease, lamotrigine was usually appropriate for both syndromes, with valproate also usually appropriate for IGE. In patients with hepatic disease, levetiracetam and lamotrigine were usually appropriate for IGE; in SLRE, levetiracetam was treatment of choice, with gabapentin also usually appropriate.Although the panel of experts reached consensus on many treatment options, there are limitations to these types of data. Despite this, the expert consensus method concisely summarizes expert opinion, and this opinion may be helpful in situations in which the medical literature is scant or lacking. The information in this report should be evaluated in conjunction with evidence-based findings.

    View details for DOI 10.1016/j.yebeh.2005.06.001

    View details for Web of Science ID 000231545500001

    View details for PubMedID 16102515

  • Sexual dysfunction, sex steroid hormone abnormalities, and depression in women with epilepsy treated with antiepileptic drugs EPILEPSY & BEHAVIOR Morrell, M. J., Flynn, K. L., Done, S., Flaster, E., Kalayjian, L., Pack, A. M. 2005; 6 (3): 360-365

    Abstract

    Women with epilepsy are believed to be at risk for sexual dysfunction. Disorders of sexual desire and sexual arousal, including dyspareunia, vaginismus, and lack of lubrication, affect an estimated 30 to 60% of women with epilepsy. In this study, 57 reproductive-aged women with either localization related (LRE) or primary generalized epilepsy (PGE) on antiepileptic drug (AED) monotherapy and 17 nonepileptic controls completed questionnaires examining sexual experience, arousability, anxiety, and symptoms, as well as an inventory of depression. An endocrine assessment was performed during the early follicular phase of the menstrual cycle. Sexual dysfunction was more common in women with LRE, in women receiving phenytoin, in women with low levels of estradiol and dehydroepiandrosterone sulfate, and in women with self-reported symptoms of mild depression. The mechanisms of sexual dysfunction in women with epilepsy are multifactorial, but AED choice appears to be one cause that is modifiable.

    View details for DOI 10.1016/j.yebeh.2005.01.004

    View details for Web of Science ID 000228626300011

    View details for PubMedID 15820344

  • Sex-steroid hormones in women with epilepsy. American journal of electroneurodiagnostic technology Jette, N., Morrell, M. J. 2005; 45 (1): 36-48

    Abstract

    Women with epilepsy face unique challenges, in part related to changes in the seizure threshold at various times in the menstrual cycle or during their reproductive life. Ovarian sex-steroid hormones alter the excitability of the central nervous system (CNS) and alter the frequency and severity of seizures. By understanding the effects of hormones on seizures, clinicians are better equipped to treat hormonally mediated epilepsy.

    View details for PubMedID 15832673

  • Bone mass and turnover in women with epilepsy on antiepileptic drug monotherapy ANNALS OF NEUROLOGY Pack, A. M., Morrell, M. J., Marcus, R., Holloway, L., Flaster, E., Done, S., Randall, A., Seale, C., Shane, E. 2005; 57 (2): 252-257

    Abstract

    Antiepileptic drugs, particularly cytochrome P450 enzyme inducers, are associated with disorders of bone metabolism. We studied premenopausal women with epilepsy receiving antiepileptic drug monotherapy (phenytoin, carbamazepine, valproate, and lamotrigine). Subjects completed exercise and nutrition questionnaires and bone mineral density studies. Serum was analyzed for indices of bone metabolism including calcium, 25-hydroxyvitamin D, parathyroid hormone, insulin growth factor I, insulin binding protein III, and bone formation markers, bone-specific alkaline phosphatase, and osteocalcin. Urine was analyzed for cross-linked N-telopeptide of type I collagen, a bone resorption marker. Calcium concentrations were significantly less in subjects receiving carbamazepine, phenytoin, and valproate than in those receiving lamotrigine (p = 0.008). Insulin growth factor-I was significantly reduced in subjects receiving phenytoin compared with those receiving lamotrigine (p = 0.017). Subjects receiving phenytoin had significantly greater levels of bone-specific alkaline phosphatase (p = 0.007). Our results demonstrate that phenytoin is associated with changes in bone metabolism and increased bone turnover. The lower calcium concentrations in subjects taking carbamazepine or valproate compared with those taking other antiepileptic drugs suggest that these antiepileptic drugs may have long-term effects. Subjects receiving lamotrigine had no significant reductions in calcium or increases in markers of bone turnover, suggesting this agent is less likely to have long-term adverse effects on bone.

    View details for DOI 10.1002/ana.20378

    View details for Web of Science ID 000226633800013

    View details for PubMedID 15668966

  • Correlating lamotrigine serum concentrations with tolerability in patients with epilepsy NEUROLOGY Hirsch, L. J., Weintraub, D., Buchsbaum, R., Spencer, H. T., Hager, M., Strake, T., Bazil, C. W., Adams, D. J., Resor, S. R., Morrell, M. J. 2004; 63 (6): 1022-1026

    Abstract

    To correlate lamotrigine (LTG) serum concentrations (levels) with tolerability in patients with epilepsy.The charts of 811 outpatients with epilepsy who had received LTG and were seen at the Columbia Comprehensive Epilepsy Center after January 1, 2000, were reviewed. Data gathered included levels, dosage, duration of use, concomitant antiepileptic drugs (AEDs), clinical toxicity, specific side effects, and efficacy. Rates of toxicity, specific side effects, and efficacy were calculated and correlated with serum levels.In total, 3,731 LTG levels were recorded. A regimen was categorized as toxic if the patient experienced side effects that led to a dosage change or discontinuation of LTG. Of 3,919 AED regimens, 9.4% were toxic and 30.7% of patients had at least one toxic regimen. Toxicity increased with increasing LTG levels (p < 0.0001): With levels <5.0 microg/mL, 7% of patients were toxic; with levels of 5 to 10 microg/mL, 14%; with 10 to 15 microg/mL, 24%; with 15 to 20 microg/mL, 34%; and with >20 microg/mL, 59%. The correlation between levels and tolerability was independent of concurrent medication. Increasing efficacy, as measured by seizure freedom for a 6-month period, occurred up to levels of >20 microg/mL.There is a correlation between LTG serum level and tolerability, independent of the use of other AEDs. Adverse effects requiring a dose change are uncommon with the most frequently encountered LTG concentrations (<10 microg/mL) and occur in only 7.4% of patients at levels obtained during the majority of clinical trials (<5 microg/mL). An initial target range of 1.5 to 10 microg/mL is suggested, though higher levels, up to >20 microg/mL, are often tolerated and can lead to additional efficacy in refractory patients.

    View details for Web of Science ID 000224128500015

    View details for PubMedID 15452293

  • Epilepsy and bone health in adults EPILEPSY & BEHAVIOR Pack, A. M., Morrell, M. J. 2004; 5: S24-S29

    Abstract

    Adults taking antiepileptic drugs (AEDs) have an augmented risk for osteopenia and osteoporosis because of abnormalities of bone metabolism associated with AEDs. The increased fracture rates that have been described among patients with epilepsy may be related both to seizures and to AEDs. The hepatic enzyme-inducing AEDs phenytoin, phenobarbital, and primidone have the clearest association with decreased bone mineral density (BMD). Carbamazepine, also an enzyme-inducing drug, and valproate, an enzyme inhibitor, may also adversely affect bone, but further study is needed. Little information is available about specific effects of newer AEDs on bone. Physicians are insufficiently aware of the association between AEDs and bone disease; a survey found that fewer than one-third of neurologists routinely evaluated AED-treated patients for bone disease, and fewer than 10% prescribed prophylactic calcium and vitamin D. Physicians should counsel patients taking AEDs about good bone health practices, and evaluation of bone health by measuring BMD is warranted after 5 years of AED treatment or before treatment in postmenopausal women.

    View details for DOI 10.1016/j.yebeh.2003.11.029

    View details for Web of Science ID 000220350200004

    View details for PubMedID 15123008

  • Reproductive disturbances in patients with epilepsy. Cleveland Clinic journal of medicine Morrell, M. J., Montouris, G. D. 2004; 71: S19-24

    Abstract

    In persons with epilepsy, both seizures and antiepileptic drugs can disturb reproductive health. For example, seizures can alter the release of hypothalamic and pituitary hormones, while some antiepileptic drugs alter concentrations of sex steroid hormones. Women with epilepsy are at increased risk for polycystic ovary syndrome and disorders of the menstrual cycle. Studies have found reduced fertility rates among men and women with epilepsy. The reasons for this reduction in fertility are likely to be both psychosocial and physiologic, and again, both epilepsy itself and antiepileptic drugs are implicated. Sexual dysfunction is common among patients with epilepsy and can have a somatic, psychological, or social basis. To provide the best care for patients with epilepsy, particularly women of reproductive age, clinicians must consider both the gender-based biology of epilepsy and the effects of antiepileptic drugs on reproductive health.

    View details for PubMedID 15379296

  • Use of levetiracetam in a population of patients aged 65 years and older: a subset analysis of the KEEPER trial EPILEPSY & BEHAVIOR Ferrendelli, J. A., French, J., Leppik, I., Morrell, M. J., Herbeuval, A., Han, J., Magnus, L. 2003; 4 (6): 702-709

    Abstract

    Levetiracetam (Keppra) was evaluated in a subset of patients aged >/=65 years (n=78) enrolled in a large (n=1030) open-label, phase IV trial (the KEEPER trial). A 4-week dose adjustment was followed by a 12-week evaluation period. An overall median reduction in partial seizures of 80.1% (n=65) was observed. Overall, 76.9% of patients were >/=50% responders, 56.9% were >/=75% responders, and 40.0% were 100% responders. Levetiracetam was well tolerated, with 42.3% of patients reporting one or more adverse events. A total of 15 patients (19.2%) experienced an adverse event that led to discontinuation. Somnolence (n=13,16.7%) and dizziness (n=7,9.0%) were the most commonly reported adverse events. Despite the limitations of the open-label study design, these data provide information regarding the use of levetiracetam as add-on therapy for the treatment of partial-onset seizures in patients >/=65 years of age, including those requiring concomitant medications.

    View details for DOI 10.1016/j.yebeh.2003.09.007

    View details for Web of Science ID 000187243300015

    View details for PubMedID 14698704

  • Working toward an epilepsy cure. Current neurology and neuroscience reports Morrell, M. J. 2003; 3 (4): 323-324

    View details for PubMedID 12930702

  • Higher androgens and weight gain with valproate compared with lamotrigine for epilepsy EPILEPSY RESEARCH Morrell, M. J., Isojarvi, J., Taylor, A. E., Dam, M., Ayala, R., Gomez, G., O'Neill, F., Tennis, P., Messenheimer, J. 2003; 54 (2-3): 189-199

    Abstract

    Valproate is used widely for the treatment of epilepsy but has been associated with hyperandrogenism, hyperinsulinemia, and dyslipidemia. The mechanism for these associations is unknown, but they have been hypothesized to be secondary to valproate-associated weight gain. This study was conducted to test the hypothesis that the antiepileptic drug lamotrigine, which also has a broad spectrum of anti-seizure efficacy, would not be associated with endocrine abnormalities and would not cause weight gain.This open-label, cross-sectional study compared (1) endocrine and lipid measures during the early follicular phase of the menstrual cycle; (2) prevalence of menstrual disorders (from patient diaries recorded over three cycles); and (3) body weight of women with epilepsy on lamotrigine monotherapy (n=119) with those on valproate monotherapy (n=103) for <5 years.Mean total serum testosterone and androstenedione levels were higher (P<0.02) in the valproate group compared with the lamotrigine group. More lamotrigine patients (87%) than valproate patients (77%) reported regular menstrual cycles at the Screening Visit. The prevalence of anovulation did not differ between lamotrigine and valproate. Mean HDL cholesterol levels were higher (P<0.01) with lamotrigine compared with valproate as were LDL and total cholesterol levels (P<0.05). Mean total insulin levels did not significantly differ between the groups. Whereas mean body weight in lamotrigine patients did not differ between the time lamotrigine treatment was initiated and the Study Visit, mean weight in valproate patients increased by 3.7 kg.Compared with lamotrigine monotherapy, valproate monotherapy was associated with weight gain and higher androgen levels in women with epilepsy. These data suggest that the hyperandrogenism observed in some women using valproate for epilepsy may be secondary to drug therapy. Lamotrigine monotherapy may be more appropriate than valproate for women in whom reproductive endocrine or metabolic abnormalities are potential concerns, i.e. women with concerns about weight gain, diabetes, hirsutism, polycystic ovary syndrome, menstrual dysfunction or infertility.

    View details for DOI 10.1016/S0920-1211(03)00085-8

    View details for Web of Science ID 000184223500012

    View details for PubMedID 12837570

  • The KEEPER (TM)(1) trial: levetiracetam adjunctive treatment of partial-onset seizures in an open-label community-based study EPILEPSY RESEARCH Morrell, M. J., Leppik, I., French, J., Ferrendelli, J., Han, J., Magnus, L. 2003; 54 (2-3): 153-161

    Abstract

    Three randomized, placebo-controlled trials have demonstrated the safety and efficacy of levetiracetam, a new antiepileptic medication, as add-on therapy for partial-onset seizures. The purpose of this study was to gather additional safety and efficacy data on levetiracetam in the real-world setting of community-based practice.This was a phase IV prospective, open-label, multicenter, community-based trial. A total of 1030 patients (intent-to-treat (ITT) population) at least 16 years old (mean, 42.2 years) with partial-onset seizures were enrolled by over 300 investigators. Patients whose partial-onset seizures were inadequately controlled on their current medications had levetiracetam 500 mg bid added to their regimens. The levetiracetam dose was increased by 500 mg bid at the end of weeks 2 and 4 to a maximum dose of 1500 mg bid, unless the patient had been seizure-free during the preceding 2-week period. The dose was then to remain the same for 12 weeks. The main outcome measures were reduction in seizure frequency, global evaluation scale (GES), and adverse events.During the 16 weeks of the trial, 57.9% (542/936) experienced at least a 50% reduction in the frequency of partial-onset seizures, 40.1% (375/936) experienced at least a 75% reduction, and 20% (187/936) demonstrated a 100% seizure reduction. During the last 6 weeks of the study, 66.7% (500/750) experienced at least a 50% reduction in the frequency of partial seizures, 52.4% (393/750) experienced at least a 75% reduction, and 42.1% (316/750) demonstrated a 100% seizure reduction. On the investigator-completed clinical impression rating (GES), 74.3% (734/988) of patients were considered improved, with 37% of patients showing marked improvement. The most common adverse events were somnolence, dizziness, asthenia, and headache; these events were predominantly mild-to-moderate in nature.These results provide further evidence regarding the efficacy and safety of levetiracetam as adjunctive treatment for partial-onset seizures.

    View details for DOI 10.1016/S0920-1211(03)00080-9

    View details for Web of Science ID 000184223500008

    View details for PubMedID 12837566

  • Bone mineral density in an outpatient population receiving enzyme-inducing antiepileptic drugs EPILEPSY & BEHAVIOR Pack, A. M., Olarte, L. S., Morrell, M. J., Flaster, E., Resor, S. R., Shane, E. 2003; 4 (2): 169-174

    Abstract

    Antiepileptic drug (AED) use is identified as being associated with increased fracture risk. AEDs commonly associated with osteopathies are inducers of the hepatic cytochrome p450 enzyme system (EIAEDs). We performed a retrospective cross-sectional study assessing bone mineral density (BMD) in an adult outpatient population receiving EIAEDs. Patients were routinely referred for dual-energy X-ray absorptiometry to evaluate BMD. BMD was measured at the femoral neck of hip and lumbar spine. Results were presented as absolute BMD (g/cm(2)), T score, and Z score. T and Z scores were used in this analysis. As a group, those with BMD measurements represent people with intractable epilepsy. There were no statistically significant differences found in the T or Z scores by gender; therefore all analyses combined both men and women. Significant reductions in both T and Z scores were present in men and women <50 and >or=50.

    View details for DOI 10.1016/S1525-5050(03)00036-2

    View details for Web of Science ID 000182633900013

    View details for PubMedID 12697142

  • Review of lamotrigine and its clinical applications in epilepsy EXPERT OPINION ON PHARMACOTHERAPY Choi, H., Morrell, M. J. 2003; 4 (2): 243-251

    Abstract

    Lamotrigine is an anti-epileptic agent with broad efficacy. Lamotrigine works at voltage-sensitive sodium channels, thereby stabilising the neuronal membrane and inhibiting the release of excitatory neurotransmitters such as glutamate and aspartate. Early preclinical animal studies indicate its broad-spectrum efficacy, which was later confirmed in clinical trials. Multiple randomised, placebo-controlled and comparative trials demonstrate its efficacy against partial and secondarily generalised seizures. Open-label trials show its efficacy against generalised seizures, especially absence seizures of childhood absence epilepsy and generalised seizures of juvenile myoclonic epilepsy. Lamotrigine has a wide clinical dose range and possesses favourable pharmacokinetic properties. It has a good tolerability and safety profile, which enhance compliance. Its small risk of serious skin rash should be weighed against its potential benefits when choosing lamotrigine on an individual basis. Lamotrigine is an excellent therapeutic option in epilepsy.

    View details for Web of Science ID 000183860400013

    View details for PubMedID 12562315

  • Reproductive and metabolic disorders in women with epilepsy EPILEPSIA Morrell, M. J. 2003; 44: 11-20

    Abstract

    Epilepsy is a common neurologic disorder affecting women during the reproductive years. Seizures and some antiepileptic drugs (AEDs) can compromise reproductive health, and some AEDs can adversely affect carbohydrate and bone metabolism. Women with epilepsy have lower birth rates and more frequent anovulatory menstrual cycles. This appears to be related to seizure- and AED-associated reproductive endocrine disturbances. Carbamazepine (CBZ), phenytoin (PHT), and phenobarbital (PB) induce hepatic cytochrome P450 enzymes and lower endogenous estrogens, adrenal and ovarian androgens, and contraceptive steroids. Valproate (VPA) inhibits steroid hormone metabolism, elevates androgens, and predisposes to phenotypic signs of hyperandrogenism-hirsutism, obesity, acne, and frequent anovulatory cycles. VPA is associated with weight gain, probably by altering insulin metabolism. CBZ, PHT, and VPA, but not lamotrigine (LTG), are associated with lower levels of calcium. PHT, but not VPA or LTG, appears to accelerate bone turnover. AED effects on bone mineral metabolism may explain the elevated risk of fracture described in women with epilepsy. Prospective pregnancy registries are beginning to provide information about AED-associated teratogenesis. The North American Antiepileptic Drug Pregnancy Registry reports a 12% rate of major malformations after first trimester exposure to PB and an 8.6% rate after first trimester exposure to VPA. A prospective LTG-specific registry reports a 1.8% chance of major malformations after the first trimester. The registries will continue to release information as data become significant. In the meantime, practitioners can be alert to signs and symptoms of reproductive or metabolic health disturbances and participate in pregnancy registry efforts.

    View details for Web of Science ID 000184150600003

    View details for PubMedID 12823565

  • Predictors of ovulatory failure in women with epilepsy ANNALS OF NEUROLOGY Morrell, M. J., Giudice, L., Flynn, K. L., Seale, C. G., Paulson, A. J., Done, S., Flaster, E., Ferin, M., Sauer, M. V. 2002; 52 (6): 704-711

    Abstract

    Women with epilepsy (WWE) are at increased risk for reproductive disorders. This study was designed to evaluate whether WWE are more likely to have anovulatory cycles and to assess the relative association of the epilepsy syndrome category and antiepileptic drugs (AEDs) to ovulatory dysfunction. Subjects included women aged 18 to 40 years not receiving hormones. Women without epilepsy (23 controls) and women with localization-related epilepsy (LRE, n = 59) or idiopathic (primary) generalized epilepsy (IGE, n = 35) receiving either a cytochrome P450 enzyme (cP450) inducing AED (carbamazepine, phenytoin, and phenobarbital), a cP450 inhibiting AED (valproate), or an AED that does not alter cP450 enzymes (lamotrigine and gabapentin) in monotherapy for 6 months or more were followed for three menstrual cycles. A transvaginal ovarian ultrasound was obtained. Endocrine and metabolic variables were measured and luteinizing hormone sampled over 8 hours on days 2 to 5 of one cycle. Anovulatory cycles occurred in 10.9% of cycles in controls, 14.3% of cycles with LRE, and 27.1% of cycles with IGE. Of women using valproate currently or within the preceding 3 years, 38.1% had at least one anovulatory cycle in contrast with 10.7% of women not using valproate within the preceding 3 years. Predictors of ovulatory failure included IGE syndrome, use of valproate currently or within 3 years, high free testosterone, and fewer numbers of luteinizing hormone pulses, but not polycystic-appearing ovaries. WWE are more likely to experience anovulatory menstrual cycles and the effects of epilepsy syndrome, and AED therapy may be additive. Women with IGE receiving valproate were at highest risk for anovulatory cycles, polycystic-appearing ovaries, elevated body mass index, and hyperandrogynism. WWE with anovulatory cycles may have no other signs of reproductive dysfunction. Therefore, clinicians must be alert to this potential complication of epilepsy.

    View details for DOI 10.1002/ana.10391

    View details for Web of Science ID 000179500500004

    View details for PubMedID 12447923

  • Epilepsy in women AMERICAN FAMILY PHYSICIAN Morrell, M. J. 2002; 66 (8): 1489-1494

    Abstract

    Epilepsy in women raises special reproductive and general health concerns. Seizure frequency and severity may change at puberty, over the menstrual cycle, with pregnancy, and at menopause. Estrogen is known to increase the risk of seizures, while progesterone has an inhibitory effect. Many antiepileptic drugs induce liver enzymes and decrease oral contraceptive efficacy. Women with epilepsy also have lower fertility rates and are more likely to have anovulatory menstrual cycles, polycystic ovaries, and sexual dysfunction. Irregular menstrual cycles, hirsutism, acne, and obesity should prompt an evaluation for reproductive dysfunction. Children who are born to women with epilepsy are at greater risk of birth defects, in part related to maternal use of antiepileptic drugs. This risk is reduced by using a single antiepileptic drug at the lowest effective dose and by providing preconceptional folic acid supplementation. Breastfeeding is generally thought to be safe for women using antiepileptic medications.

    View details for Web of Science ID 000178868300012

    View details for PubMedID 12408423

  • Women with epilepsy: current treatment strategies. The journal of gender-specific medicine : JGSM : the official journal of the Partnership for Women's Health at Columbia Karceski, S., Morrell, M. J. 2002; 5 (5): 22-26

    Abstract

    Despite an ever-growing body of medical literature on epilepsy and its treatment, there are many clinical situations in which the best approach is unclear. In these situations, physicians may turn to expert opinion for guidance. Several methods exist for summarizing expert opinion. The least biased method is also the newest: the expert consensus method. When this method is used to analyze opinion regarding the treatment of women with epilepsy, it is clear that the selection of therapy is influenced by the sex of the patient.

    View details for PubMedID 12380197

  • Treatment of women with epilepsy SEMINARS IN NEUROLOGY Pack, A. M., Morrell, M. J. 2002; 22 (3): 289-297

    Abstract

    Epilepsy is equally prevalent in men and women. However, for women there are unique concerns related to hormone effects on seizures and the effects of seizures and antiepileptic drugs (AEDs) on reproductive health. Steroid hormones affect neuronal excitability and seizure frequency. Some AEDs reduce the efficacy of oral contraceptive agents, increasing the probability of unplanned pregnancies. AEDs affect bone density. AEDs may alter reproductive hormones resulting in polycystic-appearing ovaries, anovulatory cycles, and infertility. Seizure frequency may change during pregnancy, seizures may cause pregnancy complications, some AEDs are teratogenic, and many cross into breast milk. The treatment of a woman with epilepsy must consider all these issues.

    View details for Web of Science ID 000180122600008

    View details for PubMedID 12528054

  • Antiepileptic medications for the treatment of epilepsy SEMINARS IN NEUROLOGY Morrell, M. J. 2002; 22 (3): 247-258

    Abstract

    Epilepsy is one of the most common neurological conditions encountered worldwide. The development of newer antiepileptic drugs (AEDs) has expanded over recent years, and the use of such drugs for indications other than epilepsy has also broadened. These factors insure that the majority of health care providers will be using an increasing number of AEDs in the care of their patients. Contained herein is a review of the mechanism of action of AEDs, individual drugs and their potential drug interactions, and general principles to guide the clinician in selection, implementation, and long-term monitoring of AEDs.

    View details for Web of Science ID 000180122600004

    View details for PubMedID 12528050

  • Stigma and epilepsy. Epilepsy & behavior : E&B Morrell, M. J. 2002; 3 (6S2): 21-25

    Abstract

    For individuals with epilepsy in the United States and other countries, stigma can be one of the most distressing consequences of having seizures, along with the unpredictability of future seizures and the inability to drive. The impact of stigma on the lives of epilepsy patients is far reaching, frequently including effects on interpersonal relationships, general health, employment opportunities, and overall quality of life. Education about epilepsy directed at the broader community, as well as at the individual with epilepsy, is the most effective means of addressing misperceptions and fear. Epilepsy advocacy organizations, such as the Epilepsy Foundation, are important allies in this effort.

    View details for PubMedID 12609302

  • Folic Acid and Epilepsy. Epilepsy currents / American Epilepsy Society Morrell, M. J. 2002; 2 (2): 31-34

    Abstract

    Folic acid has been a topic of discussion within the epilepsy community for several decades. Folic acid was initially suspected to be epileptogenic (1), but that concern has been resolved, as research has demonstrated that folic acid in less than supraphysiologic concentrations does not promote seizures. Epileptologists are now concerned that folic acid may be too low in persons with epilepsy taking some antiepileptic drugs (AEDs). Low serum and red blood cell levels of folic acid in women of childbearing potential increase the risk of fetal birth defects. For men and women, low levels of folic acid are associated with elevated homocysteine and an increased risk for cardiovascular disease. A convincing argument now develops that routine folic acid supplementation is important for women and men receiving AEDs.

    View details for PubMedID 15309159

  • The Expert Consensus Guideline Series Treatment of Epilepsy EPILEPSY & BEHAVIOR Karceski, S., Morrell, M., Carpenter, D. 2001; 2 (6): A1-A50
  • Future directions for epilepsy research NEUROLOGY Jacobs, M. P., Fischbach, G. D., Davis, M. R., Dichter, M. A., Dingledine, R., Lowenstein, D. H., Morrell, M. J., Noebels, J. L., Rogawski, M. A., Spencer, S. S., Theodore, W. H. 2001; 57 (9): 1536-1542

    Abstract

    The authors propose that epilepsy research embark on a revitalized effort to move from targeting control of symptoms to strategies for prevention and cure. The recent advances that make this a realistic goal include identification of genes mutated in inherited epilepsy syndromes, molecular characterization of brain networks, better imaging of sites of seizure origin, and developments in seizure prediction by quantitative EEG analysis. Research directions include determination of mechanisms of epilepsy development, identification of genes for common epilepsy syndromes through linkage analysis and gene chip technology, and validation of new models of epilepsy and epileptogenesis. Directions for therapeutics include identification of new molecular targets, focal methods of drug delivery tied to EEG activity, gene and cell therapy, and surgical and nonablative therapies. Integrated approaches, such as coupling imaging with electrophysiology, are central to progress in localizing regions of epilepsy development in people at risk and better seizure prediction and treatment for people with epilepsy.

    View details for Web of Science ID 000172161300004

    View details for PubMedID 11706087

  • Reproductive dysfunction in women with epilepsy: antiepileptic drug effects on sex-steroid hormones. CNS spectrums Morrell, M. J., Flynn, K. L., Seale, C. G., Done, S., Paulson, A. J., Flaster, E. R., Ferin, M. 2001; 6 (9): 771-?

    Abstract

    Women with epilepsy are at risk for reproductive health dysfunction. Sex-steroid hormone abnormalities have been reported in women with epilepsy, but it has been difficult to determine whether these abnormalities are due to epilepsy-related hypothalamic-pituitary axis dysfunction, or to pharmacokinetic actions of antiepileptic drugs (AEDs). Sex-steroid hormones were evaluated in 84 reproductive-aged women with epilepsy receiving an AED in monotherapy, and in 20 nonepileptic controls. Estrone, free testosterone, and androstenedione were significantly lower in subjects receiving enzyme-inducing AEDs than in nonepileptic controls. Free testosterone was significantly elevated in subjects receiving valproate compared to nonepileptic controls. Subjects with epilepsy receiving gabapentin or lamotrigine were no different from the nonepileptic controls in any of the endocrine variables. Subjects with epilepsy who are receiving AEDs that alter cytochrome P450 enzymes are at risk for significant abnormalities in sex-steroid hormones. In contrast, subjects receiving AEDs that do not alter cytochrome P450 enzymes show no differences in sex-steroid hormones compared with nonepileptic controls. With new AEDs available that do not alter cytochrome P450 enzymes, physician selection of therapy should consider not only seizure control, but also potential effects on reproductive physiology.

    View details for PubMedID 15492730

  • Epilepsy: diagnosis and treatment in the 21st century. CNS spectrums Morrell, M. J. 2001; 6 (9): 749-?

    View details for PubMedID 15489823

  • Pregnancy and antiepileptic drugs. Current neurology and neuroscience reports Morrell, M. J. 2001; 1 (4): 359-360

    View details for PubMedID 11898542

  • Adverse effects of antiepileptic drugs on bone structure - Epidemiology, mechanisms and therapeutic implications CNS DRUGS Pack, A. M., Morrell, M. J. 2001; 15 (8): 633-642

    Abstract

    Antiepileptic drugs (AEDs) were first associated with disorders of bone in both adults and children in the late 1960s. The most severe manifestations of these disorders are osteopenia/osteoporosis, osteomalacia and fractures. Bone disease has been described in several groups of patients receiving AEDs. Groups identified as being more vulnerable to AED-associated bone disease include institutionalised patients, postmenopausal women, older men and children. Radiological and histological evidence of bone disease is found in patients taking AEDs. Numerous biochemical abnormalities of bone metabolism have also been described. The severity of bone and biochemical abnormalities is thought to correlate with the duration of AED exposure and the number of AEDs used. In monotherapy, the AEDs most commonly associated with altered bone metabolism are phenytoin, primidone and phenobarbital (phenobarbitone). To date there have been no reports of altered bone metabolism in individuals receiving the newer anticonvulsants (specifically lamotrigine, topiramate, vigabatrin and gabapentin). The mechanisms of AED-associated bone disease are not clearly elucidated; however, several theories have been proposed to explain the link. No definitive guidelines for evaluation or treatment have yet been determined.

    View details for Web of Science ID 000171163600006

    View details for PubMedID 11524035

  • Health issues for women with epilepsy: A descriptive survey to assess knowledge and awareness among healthcare providers JOURNAL OF WOMENS HEALTH & GENDER-BASED MEDICINE Morrell, M. J., Sarto, G. E., Shafer, P. O., Borda, E. A., Herzog, A., Callanan, M. 2000; 9 (9): 959-965

    Abstract

    The American Academy of Neurology and the American College of Obstetricians and Gynecologists recently issued practice parameters for women with epilepsy. These parameters suggest optimal care practices. To assess knowledge of the issues covered in the parameters and to facilitate educational efforts to promote best care, the Epilepsy Foundation conducted a survey of healthcare professionals likely to provide care to women with epilepsy. The survey sampled 3535 healthcare professionals across a wide range of specialties. Most respondents did not know the specific effects of estrogen and progesterone on the seizure threshold, were not aware of menstrual-associated seizure patterns, and could not identify which antiepileptic drugs interfere with oral contraceptives. The majority of respondents did not know that women with epilepsy have higher rates of infertility, reproductive endocrine disorders, and sexual dysfunction. Most respondents did not know the frequency of birth defects in children born to women with epilepsy. Providers seeing the largest number of persons with epilepsy were more likely to have correct answers. By specialty, neurologists provided the highest number of correct responses, followed (in descending order) by endocrinologists, obstetricians/gynecologists, internal medicine physicians, family practice physicians, and pediatricians. These results suggest that women with epilepsy are not receiving adequate counseling and that care practices may not conform to those recommended.

    View details for Web of Science ID 000165592300006

    View details for PubMedID 11103095

  • Achieving best care for women with epilepsy. Epilepsy & behavior Morrell, M. J. 2000; 1 (5): 299-300

    View details for PubMedID 12609160

  • Assessment of ganaxolone's anticonvulsant activity using a randomized, double-blind, presurgical trial design EPILEPSIA Laxer, K., Blum, D., Abou-Khalil, B. W., Morrell, M. J., Lee, D. A., Data, J. L., Monaghan, E. P. 2000; 41 (9): 1187-1194

    Abstract

    A double-blind, randomized, placebo-controlled clinical trial to examine the safety, tolerability, and antiepileptic activity of ganaxolone in patients after withdrawal from other antiepileptic drugs during presurgical evaluations was performed.Fifty-two eligible patients were withdrawn from antiepileptic drugs and randomized to receive ganaxolone (24 patients) or placebo (28 patients) for up to 8 days. Ganaxolone was administered at a dose of 1500 mg/d on day 1 and 1875 mg/d on days 2 to 8. Dosing occurred three times per day: immediately after breakfast, lunch, and dinner.The primary measure of antiepileptic activity was duration of treatment before withdrawal from the trial. Kaplan-Meier curves depicted a clear separation between treatment groups, with 50% of the ganaxolone-treated patients completing the entire study, compared with 25% of patients treated with placebo. Intent-to-treat survival analyses revealed a trend toward efficacy with ganaxolone (p = 0.0795, log rank test). Covariate analyses revealed a significant treatment effect on survival time in men (p = 0.03). Post-hoc chi2 probe analyses focusing on patients who completed the entire study revealed a significant difference (p = 0.04) between treatment groups. The tolerability of ganaxolone was similar to that of placebo, with adverse events being reported by 79% of patients in the ganaxolone group and 68% of patients in the placebo group.Ganaxolone monotherapy was well tolerated for the duration of this clinical trial, and the results provide preliminary evidence that ganaxolone does have antiepileptic activity.

    View details for Web of Science ID 000089128200013

    View details for PubMedID 10999558

  • Efficacy of gabapentin as adjunctive therapy in a large, multicenter study SEIZURE-EUROPEAN JOURNAL OF EPILEPSY Morrell, M. J., McLean, M. J., Willmore, L. J., Privitera, M. D., Faught, R. E., Holmes, G. L., Magnus, L., Bernstein, P., Rose-Legatt, A. 2000; 9 (4): 241-248

    Abstract

    The objective of this study was to determine the efficacy of gabapentin as adjunctive therapy in doses required to achieve the most effective seizure control. There were 2016 patients with partial seizures requiring adjunctive therapy who received gabapentin at doses up to 3600 mg/day in this open-label, multicenter, 16-week study. Of the 1055 patients evaluable for efficacy, 573 received gabapentin < or =1800 mg/day and 482 received > 1800 mg/day as the highest dose received. For the overall efficacy evaluable population, the percentage of patients achieving at least a 50% reduction in seizure frequency was 76.0%; 46.4% of the patients were seizure free. Patients whose highest gabapentin dose did not require > 1800 mg/day had, at baseline, fewer seizures and were receiving fewer concomitant antiepileptic drugs (AEDs) at baseline than those patients requiring > 1800 mg/day. This suggests that patients requiring higher doses of gabapentin were more refractory to drug treatment at the start of the study. Gabapentin was well tolerated at all doses in this study. The results of the study demonstrate that gabapentin is effective as adjunctive therapy in patients with partial seizures whose seizures are inadequately controlled by traditional AEDs.

    View details for Web of Science ID 000087953900001

    View details for PubMedID 10880282

  • "The Scarlet E" - Epilepsy is still a burden NEUROLOGY Morrell, M. J., Pedley, T. A. 2000; 54 (10): 1882-1883

    View details for Web of Science ID 000087088000001

    View details for PubMedID 10822421

  • The role of the intracarotid amobarbital procedure in evaluation of patients for epilepsy surgery EPILEPSIA Spencer, D. C., Morrell, M. J., Risinger, M. W. 2000; 41 (3): 320-325

    Abstract

    To examine the role of the intracarotid amobarbital procedure (IAP) in the presurgical evaluation of patients with medically refractory localization-related epilepsy.We retrospectively studied 111 patients who underwent cortical resective surgery at our center between 1991 and 1996. In patients with mesial temporal lobe epilepsy (mTLE), a presurgical determination of the epileptogenic zone was compared with localization based on IAP memory asymmetry scores, and with ultimate localization after resective surgery. In patients with neocortical or mesial frontal epilepsy, the IAP was evaluated for evidence of unilateral or bilateral poor memory performance.Of 68 patients with mTLE localized by noninvasive tests, 60 had concordant lateralized memory deficits on IAP. Eight patients had lateralized memory deficits on IAP that were discordant with noninvasive tests and with localization as determined by surgical outcome. All 11 mTLE patients requiring invasive EEG monitoring were correctly lateralized by IAP, including one patient in whom the noninvasive evaluation otherwise provided false lateralization. Of 32 patients with neocortical or mesial frontal lobe epilepsy, 21 displayed memory deficits on IAP. Of 10 patients with bilateral deficits, five had mesial frontal lobe epilepsy. In 13 patients with lateralized memory deficits, seven underwent electrode implantation in the mesial temporal lobe, and four ultimately underwent resection of an epileptogenic mesial temporal lobe in addition to a neocortical resection.In patients with mTLE, lateralized memory deficits on IAP usually confirm localization provided by noninvasive tests. However, in mTLE not well lateralized by the noninvasive evaluation, and in neocortical or mesial frontal epilepsy, the IAP may provide information regarding localization that ultimately alters surgical management.

    View details for Web of Science ID 000085665200009

    View details for PubMedID 10714404

  • Qualitative block design performance in epilepsy patients ARCHIVES OF CLINICAL NEUROPSYCHOLOGY Zipf-Williams, E. M., Shear, P. K., Strongin, D., Winegarden, B. J., Morrell, M. J. 2000; 15 (2): 149-157

    Abstract

    Broken configuration errors on the WAIS-R Block Design subtest have been associated with right hemisphere brain damage. This study examined whether pre-surgical epilepsy patients with seizure foci restricted to the right hemisphere would break configuration more frequently than those with left hemisphere foci. Subjects included 38 patients with unilateral right or left hemisphere epilepsy of frontal or temporal lobe origin. The left and right hemisphere groups did not differ significantly in demographic or disease variables, IQ, or Block Design standard scores. Right hemisphere patients made more broken configurations than did those with left hemisphere foci. In the right hemisphere group, more broken configurations were associated with a lower Block Design Scaled Score and Full Scale IQ. These results suggest that the observation of broken configurations in the Block Design can assist in corroborating the seizure focus and highlight the importance of qualitative Block Design analysis.

    View details for Web of Science ID 000084900600005

    View details for PubMedID 14590558

  • Caring for People with Epilepsy: Resources for the Healthcare Provider. Epilepsy & behavior : E&B Morrell, M. J. 2000; 1 (4): S21-S24

    Abstract

    Epilepsy, a condition that affects all age groups, can have life-altering effects. The psychosocial effects of epilepsy are often as detrimental as the seizures themselves. Unfortunately, healthcare professionals often find themselves providing more care in less time and may be unable to thoroughly address these psychosocial needs. Therefore, national organizations and electronic media resources are prepared to provide information and support. For example, the Epilepsy Foundation has a broad range of educational materials available on the Internet and provides patient-to-patient support through on-line chat rooms and through a new initiative entitled the HOPE (Helping Other People with Epilepsy) Mentor Program, a program that trains individuals with epilepsy and their family members to provide education and support. Directing patients toward available reliable resources can help the time-constrained professional ensure that patients' needs for education and psychosocial support are met.

    View details for PubMedID 12609458

  • Discriminating between epileptic and nonepileptic events: The utility of hypnotic seizure induction EPILEPSIA Barry, J. J., Atzman, O., Morrell, M. J. 2000; 41 (1): 81-84

    Abstract

    To determine the validity of the Hypnotic Induction Profile (HIP) followed by seizure induction during continuous video-electroencephalographic (EEG) monitoring to discriminate between epileptic (EE) and nonepileptic events (NEE).Eighty-two patients admitted to the Stanford Comprehensive Epilepsy Center for differential diagnosis of seizure-like events were evaluated. Exclusion criteria included inability or refusal to complete the HIP, lack of a "typical" event, an IQ <70, present evidence of psychosis, or a physiological cause for NEE. Sixty-nine patients met these criteria. While undergoing continuous video-EEG monitoring, the patient completed an HIP, an inventory designed to measure the degree of hypnotizability. An attempt was then made to induce the patient's typical events under hypnosis by using a split-screen technique. An event without an EEG correlate was thought to represent an NEE. A diagnosis of NEE was made independently by the neurology team and was compared with results obtained with the hypnotic evaluation.Results for patients with EE were compared with those with NEE and a group consisting of both EE/NEE. All patients with NEE were then contrasted with the EE group. HIP scores for the EE patients indicated lower hypnotizability than the NEE group and were statistically significant when NEE patients and those with NEE/EE were combined. The sensitivity of seizure induction in the diagnosis of NEE was 77%, with a specificity of 95%.The HIP coupled with seizure induction is a useful technique to aid in the diagnosis of patients with NEE. It is sensitive and specific, and it may provide the patient with a useful behavioral tool to control NEEs. It may also furnish a conduit for long-term treatment.

    View details for Web of Science ID 000084703400014

    View details for PubMedID 10643928

  • Fenfluramine-Phentermine (Fen-Phen) and Seizures: Evidence for an Association. Epilepsy & behavior : E&B Spencer, D. C., Hwang, J., Morrell, M. J. 2000; 1 (6): 448-452

    Abstract

    Fenfluramine-phentermine combination therapy ("fen-phen") became a popular treatment for obesity in the 1990s. Although this treatment causes cardiac toxicity, use of these medications has not previously been associated with seizures. We report five cases with apparent association between use of fenfluramine-phentermine and occurrence of seizures. Three patients with a history of childhood-onset idiopathic generalized epilepsy in remission experienced a recrudescence of seizures following treatment with fenfluramine-phentermine. Two patients presented with new-onset seizures in midlife following use of fenfluramine-phentermine, and seizures persisted following discontinuation of this therapy. One of these patients restarted fenfluramine-phentermine months later, and experienced recurrent seizures. The nature of the association between fenfluramine-phentermine and seizures is uncertain from this preliminary report. There may be a specific association with idiopathic generalized epilepsies, which appeared to be overrepresented in this case series. An effect of fen-phen on seizure threshold appears most likely; however, an epileptogenic effect cannot be excluded.

    View details for PubMedID 12737835

  • Safety and tolerability of gabapentin as adjunctive therapy in a large, multicenter study EPILEPSIA McLean, M. J., Morrell, M. J., Willmore, L. J., Privitera, M. D., Faught, R. E., Holmes, G. L., Magnus-Miller, L., Bernstein, P., Rose-Legatt, A. 1999; 40 (7): 965-972

    Abstract

    To evaluate the tolerability and safety of gabapentin (GBP) as add-on therapy for seizure control.Conducted in an outpatient setting and reflecting usual practice, this study compared tolerability of GBP dosages < or = 1,800 versus >1,800 mg/day, when these doses were required to achieve the most effective seizure control. Two analyses of adverse events are presented: tolerability and safety. In the tolerability analysis, each patient served as his or her own control to compare the occurrence of adverse events at GBP < or =1,800 versus >1,800 mg/day. The safety analysis required patients to receive at least one dose of GBP and have a follow-up contact.A total of 2,216 patients enrolled in this open-label, 16-week study and were evaluable for safety. Of these, 74.0% completed the 16-week study, and 281 met the tolerability criteria. Within these 281 patients, two mutually exclusive groups were compared (a) those reporting adverse events at only < or =1,800 mg/day (low dose); and (b) those reporting adverse events at only >1,800 mg/day (high dose). Three adverse events (asthenia, headache, and dizziness) were observed in a statistically significantly larger number of patients at only the low dose than in the group reporting these same adverse events at only the high dose, suggesting that patients who tolerated GBP at < or = 1,800 mg/day did not experience a significant increase in adverse events with dosages >1,800 mg/day. Overall, 10.6% of the 2,216 patients in the safety population prematurely withdrew because of adverse events, and 3.5% discontinued because of lack of efficacy. Safety and tolerability of GBP was rated as excellent or good for 78.5% of all patients.Gabapentin doses >1,800 mg/day were as well tolerated as doses < or =1,800 mg/day and were not associated with more adverse events.

    View details for Web of Science ID 000081247200019

    View details for PubMedID 10403221

  • Guidelines for the care of women with epilepsy NEUROLOGY Morrell, M. J. 1998; 51 (5): S21-S27

    Abstract

    Antiepileptic drug (AED) selection in women of reproductive age should consider efficacy, tolerability, interactions with contraceptive medications, and teratogenicity. Women planning a pregnancy should be counseled regarding the need for compliance with therapy and the risk for birth defects. All women with epilepsy who are of childbearing potential should receive folate supplementation. Vitamin K supplementation is recommended during the final month of pregnancy. Withdrawal of AED therapy in seizure-free women can be considered before conception. Women who require AED therapy should receive AED monotherapy rather than polytherapy when at all possible. Medication changes post conception do not significantly reduce the risk for major fetal malformations and may compromise seizure control. Breastfeeding is generally safe for women taking AEDs. Menstrual disorders, reproductive endocrine disorders, ovulatory dysfunction, and infertility appear to be relatively common in women with epilepsy.

    View details for Web of Science ID 000076957500005

    View details for PubMedID 9818920

  • Analysis of prenatal and gestational care given to women with epilepsy NEUROLOGY Seale, C. G., Morrell, M. J., Nelson, L., Druzin, M. L. 1998; 51 (4): 1039-1045

    Abstract

    To assess past care practices of neurologists and obstetricians to identify areas in which practice patterns differ from currently accepted optimal care.Retrospective chart review of 155 women identified as having a diagnosis of epilepsy (or seizure disorder) who had been pregnant any time between January 1988 and December 1995 and were admitted to Stanford University Hospital for delivery. A total of 161 pregnancies (132 women) were selected for study.An obstetrician was seen at some point during the pregnancy in 99% of the pregnancies, whereas a neurologist was seen at least once in only 64% of the pregnancies. In the 3 months before conception, an obstetrician was seen in 5% of the pregnancies and a neurologist was seen in 15%. Seventy-five percent of the patients taking antiepileptic medication and 65% of the untreated patients had documentation of folate supplementation at any time during pregnancy. Vitamin K supplementation in the final month of pregnancy was documented for only 41% of those receiving antiepileptic drugs. In over one-third of the pregnancies the mother did not have a maternal serum alpha-fetoprotein measure documented and a similar percentage did not receive genetic counseling. Monitoring of the maternal serum concentration of the non-protein-bound fraction of the prescribed antiepileptic drugs was not documented.We identified specific omissions of appropriate vitamin supplementation, genetic counseling, and drug level monitoring. Educational efforts should be targeted to improve the management of pregnancy in women with epilepsy.

    View details for Web of Science ID 000076399100024

    View details for PubMedID 9781526

  • Management issues for women with epilepsy - A review of the literature NEUROLOGY Zahn, C. A., Morrell, M. J., Collins, S. D., Labiner, D. M., Yerby, M. S. 1998; 51 (4): 949-956

    Abstract

    A review of literature referable to management issues for women with epilepsy (WWE) was undertaken for the development of a practice parameter.Epilepsy is a common neurologic condition with gender-related management implications. Although reviews of this topic often focus on pregnancy-related issues for WWE, specific health concerns for WWE are present throughout all phases of reproductive life.An OVID MEDLINE literature search was conducted for 1965 to 1997 using the following key words/phrases and cross referencing: epilepsy/ seizures and pregnancy, anticonvulsants, antiepileptic drugs (AEDs), teratogenesis, oral contraceptives, birth defects, folate/folic acid, vitamin K, metabolic bone disease, and breast-feeding.Pregnancy outcome literature for WWE spans several decades. Methodology varies and interpretation is complicated by modern management strategies. Contributions of socioeconomic factors, AEDs, maternal epilepsy, and seizures during pregnancy to adverse pregnancy outcomes have not been clearly delineated. There is a biologic basis for recommendations concerning contraception, folate supplementation, vitamin K use in pregnancy, breast-feeding, metabolic bone disease, catamenial epilepsy, and reproductive endocrine disorders, but no outcome studies afford a strong evidence base for practice recommendation.WWE face health issues for which there is no available outcome literature to guide decision making. The urgent need for studies in many of these areas is highlighted by expanded treatment options with new AEDs and epilepsy surgery.

    View details for Web of Science ID 000076399100009

    View details for PubMedID 9781511

  • Issues for women with epilepsy WESTERN JOURNAL OF MEDICINE Morrell, M. J. 1998; 168 (4): 266-267

    View details for Web of Science ID 000073259300011

    View details for PubMedID 9584670

  • Issues for women in antiepileptic drug development. Advances in neurology Morrell, M. J. 1998; 76: 149-159

    View details for PubMedID 9408472

  • Effects of epilepsy on women's reproductive health EPILEPSIA Morrell, M. J. 1998; 39: S32-S37

    Abstract

    Reproductive dysfunctions are common and wide-ranging in women with epilepsy. Menstrual cycle disruption, anovulatory cycles, disturbances in hypothalamic and/or pituitary hormones, and disturbances in gonadal steroids are more common among women with epilepsy. Sexual dysfunction can present as either disorders of desire or physiologic arousal, but the most common dysfunction appears to be an inadequate initial physiologic arousal response. Reproductive dysfunctions may be due to psychologic, pharmacologic, or physiologic factors. Physicians should routinely question all women with epilepsy regarding their reproductive and sexual health. A full history, a complete physical, and laboratory evaluations with endocrinologic work-up should be performed in any woman who reports a reproductive dysfunction. Treatment and/or referral to a gynecologist or endocrinologist should be initiated as appropriate.

    View details for Web of Science ID 000078030000006

    View details for PubMedID 9915618

  • Intracranial ictal recordings in mesial frontal lobe epilepsy JOURNAL OF CLINICAL NEUROPHYSIOLOGY Toczek, M. T., Morrell, M. J., Risinger, M. W., Shuer, L. 1997; 14 (6): 499-506

    Abstract

    Localization of ictal onset in patients with medically refractory frontal lobe epilepsy is challenging even with intracranial monitoring. We present a series of nine patients with presumed mesial frontal lobe epilepsy in whom successful localization of ictal onset was achieved in most cases. Intracranial electrodes were placed over cingulate and supplementary motor cortex bilaterally, with additional electrodes placed over lateral and inferior frontal lobes as part of an evaluation for epilepsy surgery. Localization of the ictal onset was clearly defined in seven of nine patients and was characterized by a pattern of lower amplitude beta/gamma range frequencies noted in one to four adjacent electrodes arising from cingulate cortex or supplementary motor cortex in six patients. In the remaining patient, ictal onset was characterized by periodic high amplitude spike and slow-wave discharges evolving into a higher voltage faster rhythm. Electrographic onset occurred coincident with or preceded clinical findings. Ictal pattern also did not demonstrate a widespread propagation pattern in most of the recordings in which ictal onset was well localized. Precise localization of ictal onset within the mesial frontal lobe is possible. Rapid propagation to regions within and outside the frontal lobe does not always occur.

    View details for Web of Science ID 000077365900006

    View details for PubMedID 9458056

  • Gabapentin monotherapy .1. An 8-day, double-blind, dose-controlled, multicenter study in hospitalized patients with refractory complex partial or secondarily generalized seizures NEUROLOGY Bergey, G. K., MORRIS, H. H., Rosenfeld, W., Blume, W. T., Penovich, P. E., Morrell, M. J., Leiderman, D. B., Crockatt, J. G., Lamoreaux, L., Garofalo, E., Pierce, M. 1997; 49 (3): 739-745

    Abstract

    We evaluated the efficacy and safety of gabapentin administered as monotherapy in an 8-day, randomized, double-blind, dose-controlled, parallel-group, multicenter study comparing dosages of 300 and 3,600 mg/d gabapentin in 82 hospitalized patients whose antiepileptic medications had been discontinued for seizure monitoring. Seizures under study were complex partial seizures with or without secondary generalization. Patients exited the study if they experienced a protocol-defined exit event indicating lack of efficacy. Time to exit was significantly longer (p = 0.0001) and completion rate was significantly higher (53% versus 17%; p = 0.002) for patients receiving 3,600 mg/d gabapentin. Gabapentin was well tolerated by patients in both dosage groups, and no patients exited the study due to adverse events, despite rapid initiation of full dose within 24 hours. These results demonstrate that gabapentin has anticonvulsant activity and is well tolerated when administered as monotherapy in patients with refractory partial seizures.

    View details for Web of Science ID A1997XX77400019

    View details for PubMedID 9305334

  • Cortical and hippocampal volume deficits in temporal lobe epilepsy EPILEPSIA Marsh, L., Morrell, M. J., Shear, P. K., SULLIVAN, E. V., Freeman, H., Marie, A., Lim, K. O., Pfefferbaum, A. 1997; 38 (5): 576-587

    Abstract

    To use quantitative magnetic resonance imaging (MRI) methods to examine the extent of volume abnormalities in the hippocampus and in extrahippocampal brain regions in localization-related epilepsy of temporal lobe origin (TLE).Hippocampal, temporal lobe, and extratemporal lobe volumes were examined with 3-mm spin-echo coronal MRI scans in patients with unilateral TLE who were candidates for temporal lobe resection. Measures were adjusted for normal variation due to intracranial volume and age based on 72 healthy male controls. Group differences between 14 male TLE [7 left TLE (LTLE), 7 right TLE (RTLE)] patients and a subset of 49 age range-matched controls were examined with analysis of variance (ANOVA).As compared with controls, patients with TLE had smaller temporal lobe and frontoparietal region gray matter volumes, bilaterally, smaller temporal lobe white matter volumes bilaterally, and larger ventricular volumes. In contrast to these bilateral tissue volume deficits, hippocampal volume deficits in TLE were ipsilateral to the epileptogenic temporal lobe.Extrahippocampal volume abnormalities were bilateral and occurred in both temporal and extra-temporal cortical regions in TLE, whereas hippocampal deficits were related to the side of the epileptogenic focus. These data suggest that brain abnormalities in TLE are not limited to the epileptogenic region.

    View details for Web of Science ID A1997WX71900011

    View details for PubMedID 9184604

  • Maximizing the health of women with epilepsy: Science and ethics in new drug development EPILEPSIA Morrell, M. J. 1997; 38: S32-S41

    Abstract

    Issues of unique concern to women with epilepsy largely arise from gender-based physiological differences. Female sex steroid hormones may alter the expression of epilepsy and the efficacy of antiepileptic drugs (AEDs). Seizures and AEDs in turn affect the hypothalamic-pituitary axis and can adversely impact reproductive function and bone health. Maternal seizures and exposure to AEDs may compromise fetal development. At this time, women with epilepsy and their medical caretakers do not have access to all the information necessary to formulate a treatment plan that will have the least impact on reproductive and general health. In part, this is because reproductive aged women are excluded from the earliest phases of drug testing and pregnant and lactating women are excluded from all aspects of new drug development. Therefore, as new AEDs enter the marketplace, women with epilepsy must decide whether a new AED is appropriate for therapy based on very limited information. Postmarketing surveillance of gender-specific adverse effects, as with all adverse effects, depends on voluntary reporting. Only a small percentage of significant adverse events are believed to be captured by the present system. Consumers, ethicists, and some physician groups are now arguing that women should be included in all aspects of the development of drugs they will ultimately use-even pregnant and lactating women. Some of the issues of concern for women with epilepsy regarding epilepsy treatment, reproductive function and general health will be reviewed, followed by a discussion of the drug development process and how it does, and could better, address the concerns of women.

    View details for Web of Science ID A1997XM93100007

    View details for PubMedID 9240239

  • Self-reported sexual function and sexual arousability in women with epilepsy EPILEPSIA Morrell, M. J., Guldner, G. T. 1996; 37 (12): 1204-1210

    Abstract

    Women with epilepsy are at risk for sexual dysfunction but the frequency and types of dysfunction have not been well characterized.Self-reported sexual function was evaluated in 116 women aged 18-65 years with epilepsy and no concomitant medical or psychiatric illness, including 99 with localization-related epilepsy (LRE) and 17 with primary generalized epilepsy (PGE). Variables evaluated included seizure frequency, age of seizure onset, and antiepileptic drug (AED) exposure. Standardized inventories assessed sexual functioning, sexual arousability and anxiety, sexual behavior, and depression.Although sexual experience was not reduced, women with PGE and LRE reported significantly less sexual arousability and women with LRE reported significantly more sexual anxiety. Women with LRE experienced significantly more dyspareunia, vaginismus, arousal insufficiency, and sexual dissatisfaction, whereas women with PGE experienced anorgasmia and sexual dissatisfaction. Sexual symptoms were not associated with seizure frequency, AED exposure, sexual experience, depression, or prepubertal seizure onset.In contrast to subjects of previous research, the women in our study did not have a disorder of sexual desire, but more than one third experienced disorders of sexual arousal, implying a physiological deficit. Although the etiology for these arousal phase dysfunctions has not been defined, such conditions are treatable and warrant referral to a gynecologist versed in the treatment of sexual disorders.

    View details for Web of Science ID A1996VW83000009

    View details for PubMedID 8956853

  • Nocturnal penile tumescence and rigidity evaluation in men with epilepsy EPILEPSIA Guldner, G. T., Morrell, M. J. 1996; 37 (12): 1211-1214

    Abstract

    Men with epilepsy appear to have an approximately fivefold increase in risk of erectile dysfunction (ED). We attempted to determine whether ED in men with epilepsy was due to a physiological basis and whether erectile function could be adequately evaluated with an ambulatory nocturnal penile tumescence and rigidity monitor.The physiologic integrity of the sexual response in men with epilepsy and ED was assessed with an ambulatory nocturnal penile tumescence and rigidity monitor (NPTR). Six men with localization-related epilepsy of temporal lobe origin (TLE) and ED, 2 men with TLE and normal sexual function, and 1 man with nonepileptic seizures (NES) and ED underwent evaluation of nocturnal erections for at least 2 nights.Five of 6 men with TLE and complaints of ED had abnormal ambulatory NPTR evaluations. All others had normal ambulatory NPTR. All abnormal evaluations showed reduced levels of rigidity, often with normal levels of tumescence.Previous studies have shown this abnormal ambulatory NPTR pattern to be associated with neurogenic rather than vasogenic ED. Therefore, epilepsy-related ED may have a substantial neurophysiologic component.

    View details for Web of Science ID A1996VW83000010

    View details for PubMedID 8956854

  • Cerebellar hemorrhage complicating temporal lobectomy - Report of four cases JOURNAL OF NEUROSURGERY Toczek, M. T., Morrell, M. J., Silverberg, G. A., Lowe, G. M. 1996; 85 (4): 718-722

    Abstract

    Four cases of cerebellar hemorrhage complicating temporal lobectomy are presented. A case of postoperative hemorrhage located remote from the operative site as a complication of intracranial surgery is rare, especially when it involves the cerebellum after supratentorial craniotomy. In a review of the literature, the authors identified only 12 such cases, none of which was described in the setting of a temporal lobectomy. The possible etiologies for cerebellar hemorrhage in the four cases presented are examined, including the role of epidural suction drains and the position of the head during surgery. The mechanism of cerebellar hemorrhage in this series of patients is probably multifactorial. Special attention throughout the perioperative course must be given to hemodynamic, anatomical, and physiological factors that together can affect the patient negatively.

    View details for Web of Science ID A1996VJ24700033

    View details for PubMedID 8814184

  • Linear scleroderma and intractable epilepsy: Neuropathologic evidence for a chronic inflammatory process - Reply ANNALS OF NEUROLOGY Horoupian, D. S., Morrell, M., Chung, M., Sum, J. 1996; 39 (2): 278-278
  • Functional MRI measurement of language lateralization in Wada-tested patients BRAIN Desmond, J. E., Sum, J. M., Wagner, A. D., Demb, J. B., Shear, P. K., Glover, G. H., Gabrieli, J. D., Morrell, M. J. 1995; 118: 1411-1419

    Abstract

    In this study the use of functional MRI (fMRI) for measuring language lateralization non-invasively was examined. The subjects were seven patients with histories of temporal lobe epilepsy who had undergone Wada testing for pre-surgical evaluation. Four patients were left-hemisphere-dominant and three were right-hemisphere-dominant for language. They received fMRI scans while they made semantic or perceptual judgments about visually presented words. Regions of the inferior frontal gyrus (pars triangularis and pars orbitalis) and neighbouring orbital cortex, corresponding to portions of Brodmann areas 45, 46 and 47, exhibited significant increases in activation during semantic relative to perceptual judgments. Lateralization of the increases in activation were consistent with the Wada test assessments of hemispheric language dominance in each of the seven patients. These results suggest that, in addition to providing a tool for investigating human cognitive processes, fMRI has significant clinical potential as a non-invasive measure of language lateralization.

    View details for Web of Science ID A1995TQ33300004

    View details for PubMedID 8595473

  • PREDICTIVE VALUE OF THE FIRST ICTAL RECORDING IN DETERMINING LOCALIZATION OF THE EPILEPTOGENIC REGION BY SCALP SPHENOIDAL EEG EPILEPSIA Sum, J. M., Morrell, M. J. 1995; 36 (10): 1033-1040

    Abstract

    The number of seizures recorded during a noninvasive evaluation for epilepsy surgery varies across centers. We retrospectively studied the accuracy of the first recorded seizure in predicting the final localization of the epileptogenic region. Sixty-six consecutive patients undergoing continuous EEG monitoring with scalp and sphenoidal electrodes were studied. The first recorded seizure was determined to be either well localized or nonlocalized and was compared with the ultimate localization after multiple seizures were recorded. The first seizure was well localized in 28 and nonlocalized in 38 patients. In the localized group, the first seizure correctly predicted the final localization of the EEG monitoring study in 26 patients, whereas 2 patients had bilateral independent temporal seizures. In the nonlocalized group, ictal onset remained nonlocalized in 34 patients despite recording of multiple (median of five) seizures. This gave a sensitivity of 87% and specificity of 94% for the first recorded seizure to predict the final results of noninvasive EEG monitoring. We conclude that the first recorded seizure is highly predictive of the final results of prolonged noninvasive ictal EEG recordings but it cannot exclude the possibility of multiple epileptogenic foci.

    View details for Web of Science ID A1995RW17400012

    View details for PubMedID 7555954

  • INTRACEREBRAL INVOLVEMENT IN SCLERODERMA EN COUP DE SABRE - REPORT OF A CASE WITH NEUROPATHOLOGIC FINDINGS ANNALS OF NEUROLOGY Chung, M. H., Sum, J., Morrell, M. J., Horoupian, D. S. 1995; 37 (5): 679-681

    Abstract

    Linear scleroderma en coup de sabre (LScs) is a rare disorder not infrequently associated with neurologic symptoms, notably epilepsy. However, histopathologic documentation of intracerebral lesions in LScs is very limited and the etiology of the central nervous system symptoms has therefore never been convincingly established. We describe a 27-year-old woman with LScs and a longstanding history of epilepsy. Radiographic studies demonstrated a focal, intraparenchymal lesion in the left frontal lobe directly subjacent to the area of scleroderma on the forehead and scalp. The resected cerebral lesion revealed localized band-like sclerosis of the leptomeninges and associated vessels, as well as intraparenchymal calcifications and anomalous, ectatic vessels. These findings suggest that LScs may represent a neurocutaneous syndrome of vascular dysplasia similar to the Sturge-Weber syndrome, rather than a localized form of collagen vascular disease, as suggested by some.

    View details for Web of Science ID A1995RF06900018

    View details for PubMedID 7755364

  • OVULATORY FUNCTION IN EPILEPSY EPILEPSIA CUMMINGS, L. N., Giudice, L., Morrell, M. J. 1995; 36 (4): 355-359

    Abstract

    Women with epilepsy have lower fertility rates than women without epilepsy. We hypothesized that limbic dysfunction in temporal lobe epilepsy (TLE) alters the release of hypothalamic trophic hormones that secondarily affect release of the pituitary gonadotropins, causing ovulatory failure. We assessed ovulatory function over three consecutive menstrual cycles in 17 women with partial seizures arising from the temporal lobe (TLE), 7 women with primary generalized epilepsy (PGE), and 12 controls. We devised scores to reflect ovulatory function that were based on daily basal body temperature and monthly serum progesterone levels. Seizure frequency, antiepileptic drugs (AEDs), and depressive symptomatology were also evaluated. Anovulation was more frequent in subjects with TLE (35.3%) than in subjects with PGE (0%) or in controls (8.3%). Anovulatory cycles tended to occur more frequently in subjects with TLE who were treated with polytherapy than in those receiving monotherapy, but this result was not statistically significant. Seizure frequency and symptoms of depression did not affect ovulatory function. Although AED polytherapy may increase the likelihood of anovulation, our results suggest a mechanism of infertility related to temporal lobe dysfunction.

    View details for Web of Science ID A1995QQ26400006

    View details for PubMedID 7607113

  • CONTRIBUTIONS OF ANTERIOR CINGULATE CORTEX TO BEHAVIOUR BRAIN Devinsky, O., Morrell, M. J., Vogt, B. A. 1995; 118: 279-306

    Abstract

    Assessments of anterior cingulate cortex in experimental animals and humans have led to unifying theories of its structural organization and contributions to mammalian behaviour. The anterior cingulate cortex forms a large region around the rostrum of the corpus callosum that is termed the anterior executive region. This region has numerous projections into motor systems, however, since these projections originate from different parts of anterior cingulate cortex and because functional studies have shown that it does not have a uniform contribution to brain functions, the anterior executive region is further subdivided into 'affect' and 'cognition' components. The affect division includes areas 25, 33 and rostral area 24, and has extensive connections with the amygdala and periaqueductal grey, and parts of it project to autonomic brainstem motor nuclei. In addition to regulating autonomic and endocrine functions, it is involved in conditioned emotional learning, vocalizations associated with expressing internal states, assessments of motivational content and assigning emotional valence to internal and external stimuli, and maternal-infant interactions. The cognition division includes caudal areas 24' and 32', the cingulate motor areas in the cingulate sulcus and nociceptive cortex. The cingulate motor areas project to the spinal cord and red nucleus and have premotor functions, while the nociceptive area is engaged in both response selection and cognitively demanding information processing. The cingulate epilepsy syndrome provides important support of experimental animal and human functional imaging studies for the role of anterior cingulate cortex in movement, affect and social behaviours. Excessive cingulate activity in cases with seizures confirmed in anterior cingulate cortex with subdural electrode recordings, can impair consciousness, alter affective state and expression, and influence skeletomotor and autonomic activity. Interictally, patients with anterior cingulate cortex epilepsy often display psychopathic or sociopathic behaviours. In other clinical examples of elevated anterior cingulate cortex activity it may contribute to tics, obsessive-compulsive behaviours, and aberrent social behaviour. Conversely, reduced cingulate activity following infarcts or surgery can contribute to behavioural disorders including akinetic mutism, diminished self-awareness and depression, motor neglect and impaired motor initiation, reduced responses to pain, and aberrent social behaviour. The role of anterior cingulate cortex in pain responsiveness is suggested by cingulumotomy results and functional imaging studies during noxious somatic stimulation. The affect division of anterior cingulate cortex modulates autonomic activity and internal emotional responses, while the cognition division is engaged in response selection associated with skeletomotor activity and responses to noxious stimuli. Overall, anterior cingulate cortex appears to play a crucial role in initiation, motivation, and goal-directed behaviours.(ABSTRACT TRUNCATED AT 400 WORDS)

    View details for Web of Science ID A1995QP97200022

    View details for PubMedID 7895011

  • SEXUAL DYSFUNCTION IN PARTIAL EPILEPSY - A DEFICIT IN PHYSIOLOGICAL SEXUAL AROUSAL NEUROLOGY Morrell, M. J., Sperling, M. R., Stecker, M., Dichter, M. A. 1994; 44 (2): 243-247

    Abstract

    Men and women with epilepsy frequently complain of sexual dysfunction. We studied the sexual response in men and women with partial epilepsy of temporal lobe origin (TLE) by measuring genital blood flow (GBF) during sexual arousal. Nine women and eight men with TLE and 12 women and seven men as controls completed inventories for symptoms of depression, sexual experience, and sexual attitude and underwent measurement of digital pulse and GBF during alternating segments of sexually neutral and erotic videotape. Subjective ratings of arousal to the videotape were obtained. We calculated digital pulse and GBF response as the percentage increase in pulse amplitude during the erotic compared with the preceding sexually neutral film. No subject group reported symptoms of significant depression on the inventory. However, men and women with epilepsy had fewer sexual experiences than subjects without epilepsy, and women with epilepsy imagined specific sexual activities to be more anxiety-producing and less arousing than did women without epilepsy. Men and women with TLE had a diminished GBF response. The mean increase in GBF in men with TLE was 184% versus 660% for controls (p = 0.01). Women with TLE had a mean increase of 117% versus 161% for controls (p < 0.01). Digital pulse did not vary across stimulus conditions. Subjective ratings for all groups indicated moderate sexual arousal. We conclude that there is a diminution in one aspect of physiologic sexual arousal in some men and women with TLE.

    View details for Web of Science ID A1994MW89000009

    View details for PubMedID 8309566

  • DIFFERENTIAL-DIAGNOSIS OF SEIZURES NEUROLOGIC CLINICS Morrell, M. J. 1993; 11 (4): 737-754

    Abstract

    Distinguishing epileptic events from nonepileptic paroxysmal neurologic events represents a common diagnostic challenge. Syncope, either cardiac or noncardiac, can appear similar to atonic and even convulsive seizures. Breath holding and benign paroxysmal vertigo in children may be confused with epilepsy. Classic migraine, transient global amnesia, and transient ischemic attacks may resemble epileptic seizures. Sleep disorders, including nocturnal movements, parasomnias, and narcolepsy also may resemble epileptic seizures. Most movement disorders are distinguished easily from epilepsy; however, paroxysmal dyskinesias may resemble atonic or reflex seizures. The correct diagnosis can be established and appropriate treatment can be instituted by relying on routine and prolonged EEG, EKG, and sleep studies, when appropriate.

    View details for Web of Science ID A1993MG91400002

    View details for PubMedID 8272029

  • A NONINVASIVE PROTOCOL FOR ANTERIOR TEMPORAL LOBECTOMY NEUROLOGY Sperling, M. R., OCONNOR, M. J., Saykin, A. J., Phillips, C. A., Morrell, M. J., BRIDGMAN, P. A., French, J. A., GONATAS, N. 1992; 42 (2): 416-422

    Abstract

    We report the results of a protocol for choosing candidates for temporal lobectomy using a standard battery of objective tests without intracranial electrodes. We assigned each test a level of importance, and an algorithm was used to determine whether temporal lobectomy could be performed. Fifty-one patients (total pool, 103 patients) met protocol requirements and had an anterior temporal lobectomy with a mean follow-up of 39.4 months (range, 21 to 64 months), most remaining on anticonvulsant therapy. Eighty percent are seizure free, 12% have less than 3 seizures per year or only nocturnal seizures, and 8% have greater than 80% reduction in seizure frequency. One-third of patients who failed protocol criteria did not have temporal lobe seizures when studied with intracranial electrodes. We analyzed and modified the algorithm after comparing these patients with others who were poor candidates for temporal lobectomy. We conclude that this protocol is effective and recommend using such an objective algorithm.

    View details for Web of Science ID A1992HD79200028

    View details for PubMedID 1736176

  • SPEECH DURING PARTIAL SEIZURES - INTRACRANIAL EEG CORRELATES EPILEPSIA Morrell, M. J., Phillips, C. A., OCONNOR, M. J., Sperling, M. R. 1991; 32 (6): 886-889

    Abstract

    Vocalization during a seizure may help predict the location of seizure onset or identify structures ultimately involved in the seizure. Spontaneous vocalization during seizures was studied retrospectively in 22 patients with refractory complex partial seizures evaluated with bilateral intracranial electrodes. Of 22 patients, 12 vocalized during seizures. Seizures were as likely to originate from language-dominant (6/12) as from language-nondominant mesial temporal cortex (6/12). Fluent speech frequently occurred as seizure activity was recorded from language-dominant temporal lobe neocortex (6/12 seizures). Of the patients with well-localized seizure onsets who did not speak (6/10), seizures arose from both language-dominant and -nondominant mesial temporal cortex. We conclude that the presence or absence of vocalizations during a seizure does not reliably indicate the anatomic regions in which the seizure begins or spreads.

    View details for Web of Science ID A1991GU51700018

    View details for PubMedID 1743161

  • SEXUAL DYSFUNCTION IN EPILEPSY EPILEPSIA Morrell, M. J. 1991; 32: S38-S45

    Abstract

    Sexual dysfunction may arise more frequently in men and women with epilepsy than with other chronic illnesses, manifesting primarily as diminished sexual desire and potency. Studies using retrospective self-report of sexual attitude and behavior find an incidence of sexual dysfunction ranging from 14-66%. Sexual dysfunction may be more common in partial than in generalized epilepsies. Sexual dysfunction in epilepsy may result from a disturbance in social or psychological factors affecting sexual responsiveness. Alternatively, epileptiform discharges may disrupt the function of structures mediating sexual behavior, particularly the limbic cortex, or alter the release of hypothalamic or pituitary hormones. Antiepileptic drugs modulate hormone release from the hypothalamic-pituitary-gonadal axis and may have direct inhibitory effects on sexual behavior. Evidence both supports and refutes each of these etiologies in the sexual dysfunction seen with epilepsy. Specific evaluation and treatment protocols for patients with sexual dysfunction are available.

    View details for Web of Science ID A1991GU43200007

    View details for PubMedID 1959511

  • THE INFLUENCE OF AGE AND CYCLING STATUS ON SEXUAL AROUSABILITY IN WOMEN AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY Morrell, M. J., DIXEN, J. M., Carter, C. S., DAVIDSON, J. M. 1984; 148 (1): 66-71

    Abstract

    The effects of age and hormonal status on sexual response were quantitatively assessed by the use of a vaginal photoplethysmograph to measure changes in pulse amplitude in response to erotic film and fantasy. In young, regularly cycling women (mean age, 31 years) there were no significant differences in sexual response between the follicular, ovulatory, and luteal phases. The older premenopausal women (mean age, 51 years) showed responses not significantly different from those of the young cycling women. However, both the younger cycling women and older premenopausal women had significantly higher responses to erotic film than the postmenopausal women (mean age, 57 years). It was concluded that the menopause does result in a decrease in sexual response as assessed by vaginal pulse amplitude. However, it was not established that the magnitude of change noted is sufficient to cause any sexual dysfunction.

    View details for Web of Science ID A1984RZ07900013

    View details for PubMedID 6691383

Conference Proceedings


  • Epilepsy in women: the science of why it is special Morrell, M. J. LIPPINCOTT WILLIAMS & WILKINS. 1999: S42-S48

    Abstract

    Epilepsy is a common neurological disorder that may be affected by reproductive hormones and may complicate reproductive health. Many women with epilepsy experience changes in seizure frequency and severity with changes in reproductive cycles, including at puberty, over the menstrual cycle, with pregnancy and at menopause. Ovarian steroids alter neuronal excitability at the membrane and in the genome. Altered protein synthesis as a consequence of changes in RNA mediated gene transcription is one mechanism for steroid mediated effects on excitability. These genomic effects are delayed and sustained. In contrast, membrane effects are immediate and short duration. These effects are mediated at both the GABA-A and NMDA receptors. Estrogen also dynamically alters synaptic connectivity. Estrogen enhances excitability and lowers the seizure threshold, whereas progesterone enhances inhibition and increases the seizure threshold. In experimental models of epilepsy, estrogen is proconvulsant and progesterone is anticonvulsant. The net effect of these steroid actions is to alter neuronal excitability over physiological cycles. Some epilepsy syndromes are expressed or worsened at puberty. One third to one half of women with epilepsy have catamenial seizure patterns, with seizures most likely to occur in the perimenstrual period and at ovulation. More research is needed to understand the effects of menopause on epilepsy. Antiepileptic drugs may exacerbate the risk of reproductive endocrine disorders in women with epilepsy. Fertility rates are lower for women with epilepsy. Women with epilepsy are more likely to have anovulatory menstrual cycles, abnormal pituitary LH release and altered ovarian steroid concentrations. Polycystic ovaries are detected more often in women with epilepsy, particularly those on valproate. Treatment of hormone sensitive seizures relies on standard AEDs. Small trials suggest that adjunctive progesterone therapy is sometimes helpful. The newer AEDs, gabapentin and lamotrigine may have some advantages for women with epilepsy. These drugs do not alter levels of steroid hormones and do not interfere with effectiveness of hormonal contraception. Experience in pregnancy is limited. The dynamic effects of hormones on seizure expression and of seizures on reproductive health complicate the management of epilepsy in women. Newer AEDs may offer advantages for women with epilepsy in the reproductive years.

    View details for Web of Science ID 000082545600010

    View details for PubMedID 10487515

  • Dosing to efficacy with neurontin: The STEPS trial Morrell, M. J. BLACKWELL PUBLISHING. 1999: S23-S26

    Abstract

    The STEPS (Study of Titration to Effect Profile of Safety) trial, a 16-week, open-label, postmarketing multicenter study, assessed the efficacy of gabapentin as adjunctive therapy in patients with inadequately controlled partial seizures. Inclusion criteria were less restrictive than for Phase III studies, to include a population more representative of the patient population treated in clinical practice. Gabapentin was titrated up to a maximal dosage of 3600 mg/day to achieve seizure control or to tolerability. The efficacy analysis included compliant patients who had completed approximately 16 weeks of therapy (n = 1055); 573 received < or = 1800 mg/day and 482 received > or = 1800 mg/day. The average decrease in seizure frequency was 61%, the percentage of seizure-free patients was 46.35%, and the percentage of patients with a > or = 50% decrease in seizure frequency was 76.05%. The cumulative percentage of responders and of patients who were seizure free increased with each dosage increase. The results confirm that titration to efficacy is appropriate for adjunctive therapy with gabapentin in patients with partial epilepsy treated in clinical practice.

    View details for Web of Science ID 000083169700006

    View details for PubMedID 10530679

  • The new antiepileptic drugs and women: Efficacy, reproductive health, pregnancy, and fetal outcome Morrell, M. J. BLACKWELL PUBLISHING. 1996: S34-S44

    Abstract

    As new antiepileptic drugs (AEDs) become available, physicians will define their appropriate use in particular patient populations. For women, the issues include gender-specific efficacy and tolerability, including the impact of the AED on reproductive health. Women with epilepsy who are treated with established AEDs appear to be at risk for compromised bone health, for disturbances in fertility, menstrual cyclicity, ovulatory function, and sexuality and, with some AEDs, for failure of hormonal contraception. Finally, pregnancy outcome may be adversely affected by the established AEDs, all of which are human teratogens. Felbamate (FBM), gabapentin (GBP), lamotrigine (LTG), oxcarbazepine (OCBZ), tiagabine (TGB), topiramate (TPM), and vigabatrin (VGB) were reviewed. The preclinical development process had not addressed all the issues of concern to women. Although gender-specific efficacy is routinely evaluated, impact on reproductive health is not. FBM, GBP, LTG, TGB, TPM, and VGB have similar efficacy in women and men. It is not known whether the new AEDs will affect bone health, fertility, the menstrual cycle, and sexuality. FBM, GBP, LTG, TGB, and probably VGB do not interfere with hormonal contraception. Whether these new AEDs are good choices for the pregnant woman with epilepsy awaits further experience in human pregnancy. However, animal reproductive toxicology studies appear promising. The limited number of human pregnancy exposures do not, thus far, signal a significant number or particular type of adverse outcomes. However, only with improved postmarketing surveillance can essential information about teratogenic effects by acquired in an acceptably short time.

    View details for Web of Science ID A1996VU00200006

    View details for PubMedID 8941040

  • HORMONES AND EPILEPSY THROUGH THE LIFETIME Morrell, M. J. LIPPINCOTT-RAVEN PUBL. 1992: S49-S61

    Abstract

    Hormones influence brain function from gestation throughout life and may affect the seizure threshold by altering neuronal excitability. Estrogen enhances and progesterone diminishes neuronal excitability experimentally, whereas testosterone and corticosteroids have less consistent effects. Hormonal effects in the CNS also depend on the region of brain in which the hormone acts. Sites of action for most steroid hormones include the hypothalamus and limbic cortex, providing a mechanism for modulating behavior and endocrine function. Seizure patterns may change at certain life stages, perhaps as a result of alterations in hormones. At puberty, epilepsy and benign rolandic epilepsy often remit, while juvenile myoclonic and photosensitive epilepsy may arise. Other types of epilepsy do not respond predictably to events in the reproductive life or to advancing age. In some women, fluctuations in hormones over the menstrual cycle appear to increase seizure vulnerability, probably reflecting changes in relative amounts of estrogen and progesterone. Seizure patterns can be altered, for better or worse, during pregnancy. Whether this reflects the effects of hormones or changes in levels of antiepileptic drugs is not resolved. More information is needed about changes in established epilepsy at menopause and in the elderly. Better understanding of endocrine effects on seizures over a lifetime should lead to more effective epilepsy therapies.

    View details for Web of Science ID A1992KA42800008

    View details for PubMedID 1425494

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