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Biomedical subjects

Edward B Bromfield

Publications and source records attributed to Edward B Bromfield.

At least 19 recordsLinked to original sources
PubMed2006

Clinical characteristics of psychogenic nonepileptic seizure status in the long-term monitoring unit.

Patients with psychogenic nonepileptic seizures (PNES) mimicking status epilepticus (PNES-status) are at risk of iatrogenic complications. Our aim was to assess whether the population of patients with PNES who develop PNES-status are distinguishable. Retrospectively, we identified patients with PNES-status and compared them with patients with PNES without status and with patients with electroclinical status epilepticus (SE). Of 49 patients with PNES, 9 had PNES-status (18.2%) and 40 had PNES only. Compared with patients with PNES, subjects with PNES-status had taken fewer than three antiepileptic medications (P=0.016), had more than one event per week (P=0.026), were more likely to be admitted emergently to the monitoring unit (P=0.007), had shorter long-term monitoring (LTM) stays (P=0.003), and tended to be diagnosed sooner after initial presentation (P=0.058). Use of fewer than three antiepileptic drugs and emergent admission were independent predictors of PNES-status classification on logistic regression. Of 154 patients with epilepsy, 8 had SE during LTM (5.2%), significantly fewer than the proportion with PNES-status relative to PNES (P=0.008); the only clinical variable distinguishing these two groups was a baseline lower seizure frequency among the patients with epileptic seizures (P=0.045). Our results suggest that patients with PNES-status have features that differentiate them from patients with PNES without status and, to a lesser extent, from patients with epileptic seizures.

Adult↗
PubMed2006

Postictal psychosis: presymptomatic risk factors and the need for further investigation of genetics and pharmacotherapy.

BACKGROUND: Postictal psychosis (PIP), an episode of psychosis occurring after a cluster of seizures, is common and may be associated with profound morbidity, including chronic psychosis. Symptoms are often pleomorphic, involving a range of psychotic symptoms, including hallucinations and disorders of thought. PIP is treatable and may be averted if presymptomatic risk factors are considered in susceptible patients and treatment is initiated. CASE PRESENTATION: In this report, we present an illustrative case of PIP. The patient, Mr. R, presented to our emergency room with delusions and disordered thought process following a cluster of seizures. He recovered after admission, sedation and treatment with antipsychotic medication. DISCUSSION: A list of presymptomatic risk factors is established based on review of current literature. Identification of such risk factors may potentially help with prophylactic treatment; however, little empirical research exists in this area and treatment guidelines are thus far largely based on expert opinion. Further, while the neurobiology of schizophrenia is advancing at a rapid pace, largely due to advances in genetics, the pathophysiology of PIP remains largely unknown. Considering the progress in schizophrenia research in the context of the clinical features of PIP and existing studies, potential neurobiological mechanisms for PIP are herein proposed, and further genetic analyses, which may help identify those susceptible, are warranted. CONCLUSION: While PIP is an important problem that may present first to general hospital psychiatrists, as in the case presented, this topic is under-represented in the medical psychiatry literature. As discussed in this article, further research is needed to develop presymptomatic screens and treatment pathways to help prevent morbidity.

Journal Article↗
PubMed2006

Hippocampal and neocortical gamma oscillations predict memory formation in humans.

Functional magnetic resonance imaging (fMRI) of the human brain has shown that the hippocampus and the left temporal and frontal cortices play a key role in the formation of new verbal memories. We recorded electrical activity from 2349 surgically implanted intracranial electrodes in epilepsy patients while they studied and later recalled lists of common words. Using these recordings, we demonstrate that gamma oscillations (44-64 Hz) in the hippocampus and the left temporal and frontal cortices predict successful encoding of new verbal memories. This increase in gamma oscillations was not seen in other frequency bands, whose activity generally decreased during successful memory formation. These findings identify a role for gamma oscillations in verbal memory formation with the hippocampus and the left temporal and frontal cortices, the same regions implicated using noninvasive fMRI recording methods.

Adaptation, Physiological↗
PubMed2006

A clinical score for prognosis of status epilepticus in adults.

The authors derived a clinical score to predict mortality in status epilepticus (SE) from analysis of a retrospective SE cohort, using four variables available at presentation: history of seizures, age, seizure type, and consciousness impairment. Validation on a small prospective SE series (34 patients) resulted in sensitivity, 1.000; specificity, 0.643; negative predictive value, 1.000; and unweighted accuracy, 0.822. This simple clinical score may reliably identify patients surviving after SE.

Adult↗
PubMed2006

Human neocortical oscillations exhibit theta phase differences between encoding and retrieval.

We analyzed intracranial brain activity recorded from human participants during the performance of a working-memory task. We show that 6-13 Hz activity exhibits consistent phase across trials following experimental stimuli, and that this phase significantly differs between study and test stimuli. These findings suggest that oscillatory phase reflects the encoding-retrieval state of neural networks, supporting predictions of recent models of memory.[Hasselmo, M.E., Wyble, B.P., and Bodelon, C., 2002. A proposed function for hippocampal theta rhythm: Separate phases of encoding and retrieval enhance reversal of prior learning. Neural Comput. 14 793-817.; Judge, S.J., Hasselmo, M.E., 2004. Theta rhythmic stimulation of stratum lacunosum-moleculare in rat hippocampus contributes to associative LTP at a phase offset in stratum radiatum. J. Neurophys. 92 1516-1624.].

Adolescent↗
PubMed2006

Determinants of success in the use of oral levetiracetam in status epilepticus.

The use of new antiepileptic drugs for treatment of status epilepticus (SE) has not been studied systematically, particularly with respect to response predictors, the possibility of a dose-response relationship, and the efficacy of administration through a nasogastric tube. We analyzed 23 patients with SE treated with levetiracetam (LEV). The median daily dose of LEV was 2000 mg (range: 750-9000 mg). Ten patients (43%) responded; all had received LEV within 4 days after the beginning of their SE episode (P=0.019 vs nonresponders), and were administered less than 3000 mg LEV/day (P=0.046). No demographic or etiological variable was predictive. Among 16 patients given LEV through a nasogastric tube, administration was successful in 5; blood levels in 2 nonresponders were within or above the range 5-30 microg/mL. These data suggest that LEV may be a useful alternative in SE if administered early, even in intubated patients, and that escalating the dosage beyond 3000 mg/day will unlikely provide additional benefit.

Administration, Oral↗
PubMed2006

Complex inheritance and parent-of-origin effect in juvenile myoclonic epilepsy.

BACKGROUND: Juvenile myoclonic epilepsy (JME) is an idiopathic generalized epilepsy (IGE) with complex inheritance. Previous studies have suggested maternal inheritance and female excess in IGEs but have not been specific for JME. We investigated evidence for maternal inheritance, female excess and patterns of familial seizure risk in a well-characterized sample of JME families. METHODS: We ascertained 89 families through a JME proband and 50 families through a non-JME IGE proband. JME families were divided into those with and without evidence of linkage to the EJM1 susceptibility locus on chromosome 6. We analyzed transmission in 43 multigenerational families, calculated the adjusted sex ratio for JME, and looked for evidence of seizure specific risk in 806 family members. RESULTS: We found evidence for preferential maternal transmission in both EJM1-linked and unlinked families (2.7:1), evidence even more marked when potential selection factors were excluded. The adjusted female: male risk ratio was very high in JME (RR=12.5; 95% CI: 1.9-83.7). Absence seizures in JME probands increased the overall risk of seizures in first degree relatives (15.8% vs. 7.0%, P=0.011), as well as first-degree relatives' specific risk of absence seizures (6% vs. 1.6%, P=0.01), but not myoclonic seizures. CONCLUSIONS: We have confirmed the finding of maternal inheritance in JME, which is not restricted to JME families linked to the EJM1 locus. The striking female excess in JME may relate to anatomical and/or endocrine sexual dimorphism in the brain. Evidence for independent inheritance of absence and myoclonic seizures in JME families reinforces a model in which combinations of loci confer susceptibility to the component seizure types of IGE.

Chromosomes, Human, Pair 6↗
PubMed2006

Differential effects of antiepileptic drugs on neuroactive steroids in men with epilepsy.

PURPOSE: To compare serum levels of neuroactive steroids among men with epilepsy who take various antiepileptic drugs, untreated men with epilepsy and normal controls (NC). METHODS: Subjects were 85 men with localization-related epilepsy [unmedicated >6 months (No Rx)-10, carbamazepine (CBZ)-25, phenytoin (PHT)-25, lamotrigine (LTG)-25] and 25 NC. Sexual function scores (S-Score), hormone levels [dehydroepiandrosterone sulfate (DHEAS), bioactive (BA) testosterone (T), estradiol (BAE), and androstanediol (BAL)] and the ratios of inhibitory to excitatory neuroactive metabolites of T, i.e., BAL/BAE, were compared among groups. RESULTS: S-scores, DHEAS, and bioactive testosterone (BAT) were significantly (p < 0.05) lower and BAL and BAL/BAE were significantly higher among CBZ and PHT groups than among NC and LTG groups. LTG did not differ from NC in any of these measures. BAT correlated significantly with BAL/BAE for PHT (r = 0.44, p = 0.02) and CBZ (r = 0.42, p = 0.03) but not for NC (r = 0.03, p = NS) and LTG (r = 0.06, p = NS) groups. CONCLUSIONS: In comparison to LTG, enzyme inducing AEDs (CBZ, PHT) are associated with a more favorable neuroactive steroid balance (lower DHEAS and higher BAL/BAE) for seizure management, but at the expense of reduced serum bioavailable testosterone levels and sexual function.

Adolescent↗
PubMed2005

Levetiracetam in the treatment of status epilepticus in adults: a study of 13 episodes.

Treatment of status epilepticus (SE) has changed little over the last two decades, but the burden of this condition remains important. There is thus a need for alternative pharmacological therapies. Levetiracetam (LEV) has a wide spectrum of action and a favorable pharmacokinetic profile; however, little data exist regarding its use in SE. We identified patients with SE who received LEV, in a database comprising 127 SE episodes. Demographic, clinical and pharmacological data were analyzed, and compared to a control group consisting of 2 subjects from the database for each LEV patient, matched for age and sex. We identified 13 SE episodes occurring in 12 patients (10% of the database). Demographic, etiologic and clinical characteristics and outcome did not differ between the groups. Daily LEV dose ranged between 1,000-6,000 mg. Three patients were probable responders (23%), 1 responded to the treatment but subsequently died (8%), 4 were non-responders (31%, 1 died), and 5 had an undetermined response (38%). LEV may represent a useful alternative in the treatment of SE, particularly if a parenteral form of administration becomes available; to better define its role in this setting, prospective studies are needed.

Adult↗
PubMed2005

Refractory status epilepticus: effect of treatment aggressiveness on prognosis.

BACKGROUND: Administration of antiepileptic drugs for coma induction in refractory status epilepticus (RSE) has not been widely studied. Moreover, the effect on outcome of electroencephalographic (EEG) burst suppression remains unclear. OBJECTIVE: To investigate whether various coma-inducing options are associated with different prognoses after RSE. DESIGN: Retrospectively assessed case series. SETTING: Two tertiary referral hospitals in Boston, Mass. PATIENTS: Among 127 consecutive episodes (107 patients) of status epilepticus, we identified episodes that were refractory to first-line and second-line antiepileptic drugs, needing induced coma with barbiturates, propofol, or midazolam for clinical management. MAIN OUTCOME MEASURES: Short-term mortality and prevalence of return to functional baseline after the acute episode of status epilepticus were analyzed in relation to demographic and clinical variables and to treatment option (antiepileptic agents and EEG burst suppression). RESULTS: Forty-nine episodes of RSE (47 patients) were found, occurring more frequently in incident than in recurrent episodes of status epilepticus (P = .06). Mortality was 23% for patients with RSE and 8% for those without RSE (P = .05). Return to baseline occurred more often in the non-RSE group (P = .04). In 20 (61%) of 33 monitored episodes, EEG burst suppression was achieved. Demographic data, clinical variables, and outcome did not differ significantly with the various coma-inducing agents or between episodes with and without EEG burst suppression. CONCLUSIONS: Refractory status epilepticus is more prevalent in incident than in recurrent status epilepticus and is associated with higher mortality; clinical status is less likely to return to baseline than with non-RSE. Outcome was independent of the specific coma-inducing agents used and the extent of EEG burst suppression, suggesting that the underlying cause represents its main determinant.

Aged↗
PubMed2005

Simple partial seizures with hemisensory phenomena and dysgeusia: an insular pattern.

Insular seizures are rarely described, in part owing to the complex anatomy of this brain region. We present a patient with simple partial seizures, recorded intracranially, originating in the right insula and characterized by dysgeusia and contralateral somatosensory phenomena. This rare clinical pattern seems to be characteristic of the insula and may be undetectable with surface EEG.

Adult↗
PubMed2005

Characteristics of male veterans with psychogenic nonepileptic seizures.

PURPOSE: To describe male patients (pts) with psychogenic nonepileptic seizures (PNESs) followed up in a Veteran's Administration (VA) seizure clinic and to compare them with those with epileptic seizures (ESs) by using clinical, and psychosocial variables. METHODS: Adult male veterans seen between 1997 and 2000 with ESs were compared with those with PNESs with respect to clinical history (head trauma, antiepileptic drug exposure, depression, anxiety, substance abuse, seizure description), documented chronic pain, posttraumatic stress disorder (PTSD), compensation for diagnosis, neurologic examination, and test results including imaging and EEG data. RESULTS: Men with PNESs were younger and reported more frequent events, and diagnoses of chronic pain, anxiety, and PTSD were significantly greater. Neuroimaging [computed tomography (CT) or magnetic resonance imaging (MRI) of the brain] and neurologic examination were significantly more likely to be normal or nonspecific in pts with PNESs, although history of ictal urinary incontinence or service-connected compensation for diagnosis did not distinguish the groups. CONCLUSIONS: Male veterans with PNESs have characteristics similar to those reported in the literature, even though younger women have dominated previously studied populations. Compared with men with ESs, those with PNESs are more likely to have chronic pain, anxiety, and PTSD, as well as normal examinations and brain imaging.

Adult↗
PubMed2004

Malic enzyme 2 may underlie susceptibility to adolescent-onset idiopathic generalized epilepsy.

Idiopathic generalized epilepsy (IGE) is a class of genetically determined, phenotypically related epilepsy syndromes. Linkage analysis identified a chromosome 18 locus predisposing to a number of adolescent-onset IGEs. We report a single-nucleotide polymorphism (SNP) association analysis of the region around the marker locus with the high LOD score. This analysis, which used both case-control and family-based association methods, yielded strong evidence that malic enzyme 2 (ME2) is the gene predisposing to IGE. We also observed association among subgroups of IGE syndromes. An ME2-centered nine-SNP haplotype, when present homozygously, increases the risk for IGE (odds ratio 6.1; 95% confidence interval 2.9-12.7) compared with any other genotype. Both the linkage analysis and the association analysis support recessive inheritance for the locus, which is compatible with the fact that ME2 is an enzyme. ME2 is a genome-coded mitochondrial enzyme that converts malate to pyruvate and is involved in neuronal synthesis of the neurotransmitter gamma-aminobutyric acid (GABA). The results suggest that GABA synthesis disruption predisposes to common IGE and that clinical seizures are triggered when mutations at other genes, or perhaps other insults, are present.

Adolescent↗
PubMed2004

Day/night patterns of focal seizures.

PURPOSE: In many patients with epilepsy seizures occur with a day/night pattern. Our aims were to compare day/night patterns in seizure frequency among patients with different epileptogenic regions. METHODS: We analyzed video-EEG recordings in 15 patients with temporal lobe (TLE) and 11 with extratemporal lobe epilepsy (XTLE). Each seizure was classified according to subject group (TLE vs XTLE), sleep/wake state, and time of day of seizure occurrence (grouped into 6 x 4-hour "bins"). RESULTS: Of 90 seizures, 41 occurred in TLE and 49 in XTLE patients. There were day/night patterns of seizure occurrence in each group, with differences in the patterns between groups. In TLE, 50% of seizures occurred between the hours of 15:00 and 19:00 (17% would be expected by chance in each 4-hour "bin": F=3.59, P<0.006). In XTLE, there was a peak between 19:00 and 23:00 (47%: F=4.72, P<0.0018). The effect of time on seizures was least pronounced in the XTLE patients who had more than one epileptogenic region. The proportion of seizures occurring from sleep was significantly less in TLE (19%) than in XTLE patients (41%) [P<0.04, Fisher's exact test]. CONCLUSIONS: There are clear day/night patterns of seizure occurrence in epilepsy, with differences in the patterns between TLE and XTLE. There is an additional interaction with sleep/wake state, with relatively few seizures occurring from sleep in TLE compared with XTLE. Thus, it appears that both sleep/wake state and day/night or circadian rhythms may affect seizure proclivity, with different effects depending on the location of the epileptogenic region.

Adult↗
PubMed2004

Differential effects of antiepileptic drugs on sexual function and reproductive hormones in men with epilepsy: interim analysis of a comparison between lamotrigine and enzyme-inducing antiepileptic drugs.

PURPOSE: We compared sexual function and reproductive hormone levels among men with localization-related epilepsy (LRE) taking various antiepileptic drugs (AEDs) and normal controls (NC). METHODS: Subjects were 63 men with LRE [enzyme-inducing (EI) AEDs, 36; lamotrigine (LTG), 18; no AEDs, 9] and 18 NC. Sexual interest and function (S-score), hormone levels [bioactive testosterone (BAT) and estradiol (BAE)], hormone ratios [BAT/BAE], and gonadal efficiency [BAT/luteinizing hormone (LH)] were compared among the groups. RESULTS: S-scores, BAT levels, BAT/BAE, and BAT/LH were significantly lower in the EIAED group than in NC or LTG groups. Sex hormone-binding globulin (SHBG) was significantly higher in the EIAED group than in all other groups. Of men with LRE, 23.8% had abnormally low S-scores: 33.3% taking EIAEDs, 5.5% taking LTG, and 22.2% taking no AEDs (p < 0.01). BAT was low in 55.6% taking EIAEDs as compared with 33.3% taking LTG and 33.3% taking no AEDs (p < 0.05). Among men with low S-scores, 86.7% had low BAT as compared with 33.3% of men with normal scores (p < 0.01). BAT decline with age was greater among men with LRE than in controls (3.75 vs. 1.80 ng/dl/yr). The slope showed no significant difference among LRE groups. However, 89% of 40- to 50-year-old men taking EIAEDs had low BAT as compared with 33% taking LTG and 33% taking no AED (p < 0.01). CONCLUSIONS: Sexual function, BAT levels, BAT/BAE, and gonadal efficiency are greater with LTG than with EIAED. Abnormally low BAT levels are reached at an earlier age with EIAEDs than with LTG.

Adolescent↗
PubMed2004

Epilepsy in patients with brain tumors and other cancers.

Epilepsy is common among patients with supratentorial, especially slow-growing tumors. Several newer antiepileptic drugs have fewer side effects and drug interactions than do older drugs. Seizure control, however, may require complete lesion resection, with or without removal of an additional "epileptogenic zone." Among patients with systemic cancer, parenchymal or leptomeningeal metastases can cause epilepsy, and potentially reversible medical and neurologic perturbations can lead to acute symptomatic seizures.

Anticonvulsants↗
PubMed2002

Intraoperative magnetic resonance for the surgical treatment of lesions producing seizures.

Seizures are a major presenting feature of several non-neoplastic cerebral lesions. We reviewed the experience at the Brigham and Women's Hospital, Boston, on the surgical management of benign intracerebral lesions presenting with seizures with intraoperative magnetic resonance imaging (iMRI) guidance. Our aim was to demonstrate that this is an effective and efficient treatment for these lesions. The histories of thirteen patients who presented with seizures secondary to benign intraaxial lesions treated by craniotomy and resection within the iMRI unit at our institution were reviewed. The surgical results, histology and clinical outcomes were reviewed. The mean follow-up was 22.1 months (range 2-48). In all cases, lesions were accurately located with iMRI. After initial macroscopic resection, 5 cases were found to have residual lesion. All had complete radiological resection at the end of the procedure. At follow-up, five patients had no seizures, 5 had rare seizures and the remaining 3 had worthwhile improvement in seizure frequency. Intraoperative MRI is a safe and effective adjunct for the surgical treatment of benign intracerebral lesions presenting with seizures. It provides effective and efficient intraoperative guidance for planning and approach to the lesion and the assurance that the lesion is totally removed. Surgical resection with iMRI may, therefore, provide a useful approach to these lesions.

Adolescent↗