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Susan S Spencer

Publications and source records attributed to Susan S Spencer.

At least 19 recordsLinked to original sources
PubMed2006

On the use of bipolar montages for time-series analysis of intracranial electroencephalograms.

OBJECTIVE: Bipolar montages are routinely employed for the interpretation of scalp and intracranial EEGs (icEEGs). In this manuscript we consider the assumptions that support the use of a bipolar montage and question the universal appropriateness of bipolar representation of icEEGs for the time-series analysis of these signals. Bipolar montages introduce an element of spatial processing into the observed time-series. In the case of icEEGs, we argue ambiguity may be introduced in some settings through this operation because of a lack of certifiability of local differentiability and continuity of the spatial structure of icEEGs, and their suboptimal spatial sampling. METHODS: Example icEEGs were collected from three patients being studied for possible resective epilepsy surgery. Referential and bipolar representations of these signals were subjected to different visual and time-series analysis. The time-series measures calculated were the power spectral density and magnitude squared coherence. RESULTS: Visual analysis and time-series measures revealed that the icEEG time-series was altered by the use of a bipolar montage. The changes resulted from either the introduction of unrelated information from the two referential time-series into the bipolar time-series, or from the removal or alteration of information common to the two referential time-series in the bipolar time-series. The changes could not be predicted without prior knowledge of the relationship between measurement sites that form the bipolar montage. CONCLUSIONS: In certain settings, bipolar montages alter icEEGs and can confound the time-series analysis of these signals. In such settings, bipolar montages should be used with caution in the time-series analysis of icEEGs. SIGNIFICANCE: This manuscript addresses the representation of the intracranial EEG for time-series analysis. There may be contexts where the assumptions underpinning correct application of the bipolar montage to the intracranial EEG are not satisfied.

Brain↗
PubMed2006

GAT1 and GAT3 expression are differently localized in the human epileptogenic hippocampus.

The gamma amino butyric acid (GABA) transporters GAT-1 and GAT-3 were localized by immunohistochemistry in hippocampi removed for the control of medically intractable temporal lobe epilepsy (TLE). The study aimed to determine the relationship of GABA transporter expression to known patterns of hippocampal hyperexcitability and extracellular GABA levels. GAT-1 was localized in axon terminals and small neuronal cell bodies, and in non-sclerotic hippocampi was strongly expressed throughout all regions of the hippocampal formation. In the epileptogenic hippocampus exhibiting Ammon's horn sclerosis, immunoreactivity was reduced in the sclerotic regions CA3 and CA1, and around the cell bodies of dentate granule cells, but was increased along granule cell dendrites. GAT-3 was weakly expressed, if at all, in non-sclerotic hippocampi, but more prominently expressed in sclerotic hippocampi. GAT-3 expression was confined to cells resembling protoplasmic astrocytes, which were located in regions of relative neuronal sparing such as the dentate gyrus and hilus of the sclerotic hippocampus. The reduction in GAT-1 around granule cells in the sclerotic hippocampus could explain the prolonged GABA responses in this region. The loss of GAT-1 (a marker of GABAergic terminals) would also suggest a reduced GABAergic input to the granule cells, thus facilitating hyperexcitability. The increased GAT-3 expression in astrocytes in regions of relative neuronal sparing in the sclerotic hippocampus may be related to the overall low levels of extracellular GABA observed in the sclerotic hippocampus and their increased excitability.

Adolescent↗
PubMed2006

Reduction of AEDs in postsurgical patients who attain remission.

PURPOSE: Little evidence guides practice regarding the reduction of antiepileptic drugs (AEDs) in individuals who achieve significant periods of remission after resective surgery. METHODS: In a prospective study of 396 individuals who underwent resective surgery for intractable seizures, the impact of reducing AEDs on relapse and predictors of relapse were examined. RESULTS: Of 301 study subjects who attained a 1-year seizure remission after surgery, 129 reduced from two to one or from one to no AEDs after achieving remission, and 162 did not reduce drugs. Ten patients who stopped all AEDs before attaining remission were excluded from analysis. In all, 114 (39%) patients relapsed: 73 (45%) of 162 in the nonreduction group and 41 (32%) of 129 in the reduction group (p = 0.02). Patients who reduced drugs were more likely to have remitted immediately after hospital discharge (p<0.0001). After adjustment for this factor, little or no apparent impact of drug reduction on the rate of relapse was noted [rate ratio (RR), 1.1; 95% CI, 0.72-1.71; p=0.64 for reducing from two to one AED, and RR, 0.85; 95% CI, 0.50-1.45; p=0.56 for reducing from one to no AEDs]. Within the 129 patients who reduced AEDs, only delayed remission after hospital discharge was significantly associated with an increased rate of relapse (RR, 2.26; 95% CI, 1.15- 4.48; p=0.02). Continued auras had a marginally significant association with relapse (RR, 2.06; p=0.07) CONCLUSIONS: Although many relapses in this cohort of postsurgical patients who achieved remission occurred in the context of reducing or completely eliminating AEDs, the risk was no higher than in those who continued AEDs. Randomized studies are needed to test the impact of drug reduction in seizure-free postsurgical patients.

Adult↗
PubMed2006

Differential glutamate dehydrogenase (GDH) activity profile in patients with temporal lobe epilepsy.

PURPOSE: Pathophysiologic mechanisms underlying temporal lobe epilepsy (TLE) are still poorly understood. One major hypothesis links alterations in energy metabolism to glutamate excitotoxicity associated with seizures in TLE. The purpose of this study was to determine whether changes in the activities of enzymes critical in energy and neurotransmitter metabolism contributed to the alterations in metabolic status leading to the excitotoxic effects of glutamate. METHODS: Activities of four key enzymes involved in energy metabolism and glutamate cycling in the brain [aspartate aminotransferase (AAT), citrate synthase (CS), glutamate dehydrogenase (GDH), and lactate dehydrogenase (LDH)] were measured in anterolateral temporal neocortical and hippocampal tissues obtained from three different groups of medically intractable epilepsy patients having either mesial, paradoxical, or mass lesion-associated temporal lobe epilepsy (MTLE, PTLE, MaTLE), respectively. RESULTS: We found that GDH activity was significantly decreased in the temporal cortex mainly in the MTLE group. A similar trend was recognized in the hippocampus of the MTLE. In all three patient groups, GDH activity was considerably lower, and AAT and LDH activities were higher in cortex of MTLE as compared with the corresponding activities in hippocampus (p<0.05). In the MTLE cortex and hippocampus, GDH activities were negatively correlated with the duration since the first intractable seizure. CONCLUSIONS: Our results support the hypothesis suggesting major alteration in GDH activity mainly in the MTLE group. It is proposed that significant alterations in the enzyme activities may be contributing to decreased metabolism of glutamate, leading to its accumulation.

Adolescent↗
PubMed2006

Epilepsy in North America: a report prepared under the auspices of the global campaign against epilepsy, the International Bureau for Epilepsy, the International League Against Epilepsy, and the World Health Organization.

In North America, overall epilepsy incidence is approximately 50/100,000 per year, highest for children below five years of age, and the elderly. The best data suggest prevalence of 5-10/1000. Potential effects of gender, ethnicity, access to care and socioeconomic variables need further study. Studies of epilepsy etiology and classification mainly were performed without modern imaging tools. The best study found an overall standardized mortality ratio (SMR) for epilepsy relative to the general population of 2.3. There is evidence to suggest a greater increase in patients with symptomatic epilepsy, particularly children. People with epilepsy are more likely to report reduced Health-related Quality of Life than controls. They have reduced income, and are less likely to have full-time employment. They suffer from persistent stigma throughout the region, in developed as well as developing countries. Poor treatment access and health care disparities for people with epilepsy may be related to insufficient economic resources, rural isolation, gender, ethnicity, and lack of public and physician knowledge of modern approaches to epilepsy care. Despite high costs and severe disability, epilepsy may attract somewhat less research funding from public and private sources than other less common chronic neurological disorders. A Plan for Epilepsy in North America should address: basic and clinical research; primary prevention research; translation to care; stigma, quality of life, and self-management; industry relations; government and regional relations; and regional integration and resource sharing.

Epilepsy↗
PubMed2005

Localizing value of ictal-interictal SPECT analyzed by SPM (ISAS).

PURPOSE: The goal of neuroimaging in epilepsy is to localize the region of seizure onset. Single-photon emission computed tomography with tracer injection during seizures (ictal SPECT) is a promising tool for localizing seizures. However, much uncertainty exists about how to interpret late injections, or injections done after seizure end (postictal SPECT). A widely available and objective method is needed to interpret ambiguous ictal and postictal scans, with changes in multiple brain regions. METHODS: Ictal or postictal SPECT scans were performed by using [99mTc]-labeled hexamethyl-propylene-amine-oxime (HMPAO), and images were analyzed by comparison with interictal scans for each patient. Forty-seven cases of localized epilepsy were studied. We used methods that can be implemented anywhere, based on freely downloadable software and normal SPECT databases (http://spect.yale.edu). Statistical parametric mapping (SPM) was used to localize a single region of seizure onset based on ictal (or postictal) versus interictal difference images for each patient. We refer to this method as ictal-interictal SPECT analyzed by SPM (ISAS). RESULTS: With this approach, ictal SPECT identified a single unambiguous region of seizure onset in 71% of mesial temporal and 83% of neocortical epilepsy cases, even with late injections, and the localization was correct in all (100%) cases. Postictal SPECT, conversely, with injections performed soon after seizures, was very poor at localizing a single region based on either perfusion increases or decreases, often because changes were similar in multiple brain regions. However, measuring which hemisphere overall had more decreased perfusion with postictal SPECT, lateralized seizure onset to the correct side in approximately 80% of cases. CONCLUSIONS: ISAS provides a validated and readily available method for epilepsy SPECT analysis and interpretation. The results also emphasize the need to obtain SPECT injections during seizures to achieve unambiguous localization.

Adolescent↗
PubMed2004

Positive and negative network correlations in temporal lobe epilepsy.

Temporal lobe seizures are accompanied by complex behavioral phenomena including loss of consciousness, dystonic movements and neuroendocrine changes. These phenomena may arise from extended neural networks beyond the temporal lobe. To investigate this, we imaged cerebral blood flow (CBF) changes during human temporal lobe seizures with single photon emission computed tomography (SPECT) while performing continuous video/EEG monitoring. We found that temporal lobe seizures associated with loss of consciousness produced CBF increases in the temporal lobe, followed by increases in bilateral midline subcortical structures. These changes were accompanied by marked bilateral CBF decreases in the frontal and parietal association cortex. In contrast, temporal lobe seizures in which consciousness was spared were not accompanied by these widespread CBF changes. The CBF decreases in frontal and parietal association cortex were strongly correlated with increases in midline structures such as the mediodorsal thalamus. These results suggest that impaired consciousness in temporal lobe seizures may result from focal abnormal activity in temporal and subcortical networks linked to widespread impaired function of the association cortex.

Adolescent↗
PubMed2004

An approach to the evaluation of a patient for seizures and epilepsy.

Epilepsy affects approximately 1 percent of the population and is characterized by recurrent unprovoked seizures. A careful clinical history is often helpful in diagnosis, classification of seizure and epilepsy types, selection of appropriate ancillary studies, selection of anti-epileptic drugs, and formulation of a long-term management plan. This article provides directions and guidelines both for the family practice physician and the specialist in evaluating this patient population in the clinics.

Diagnosis, Differential↗
PubMed2003

Temporal lobe tumoral epilepsy: characteristics and predictors of surgical outcome.

OBJECTIVE: To review the clinical and neurophysiologic features and surgical outcome in patients with intractable temporal lobe tumoral epilepsy. METHODS: Patients with intractable temporal lobe epilepsy who underwent resection of temporal lobe tumors, confirmed by surgical pathology, seen between 1985 and 2000 at Yale University School of Medicine Epilepsy Center, were selected. Medical records were reviewed for age at diagnosis, age at onset of seizures, delay between seizure onset and tumor diagnosis, types and frequencies of seizures, EEG results, use of anticonvulsants, extent of surgery, and pathologic diagnosis. RESULTS: Sixty-eight patients were identified, 94.1% of them with low-grade tumors. Complex partial seizure was the most common seizure type. All patients underwent at least one surgical procedure with average follow-up of 9 years after surgical intervention. Eighty-seven percent of patients had significant postoperative seizure improvement (Engel's classes I and II). Gross total tumor resection predicted postoperative seizure freedom (p = 0.002), whereas patients with early surgical intervention, auras, and simple partial seizures had a tendency toward better seizure outcome. CONCLUSIONS: Long-term follow-up of patients with intractable temporal lobe tumoral epilepsy suggests good response of seizures to surgery, which is unrelated to age at diagnosis, EEG, or pathology. Extent of tumor resection was significantly predictive of outcome, whereas early intervention and presence of simple partial seizures showed trends as predictive factors.

Adolescent↗
PubMed2003

Selective frontal, parietal, and temporal networks in generalized seizures.

Are "generalized" seizures truly generalized? Generalized tonic-clonic seizures are classified as either secondarily generalized with local onset or primarily generalized, without known focal onset. In both types of generalized seizures widespread regions of the nervous system engage in abnormally synchronous and high-frequency neuronal firing. However, emerging evidence suggests that all neurons are not homogeneously involved; specific nodes within the network may be crucial for the propagation and behavioral manifestations of generalized tonic-clonic seizures. Study of human tonic-clonic seizures has been limited by problems with patient movement and variable seizure types. To circumvent these problems, we imaged generalized tonic-clonic seizures during electroconvulsive therapy, in which seizure type and timing are well controlled. (99m)Tc-hexamethylpropylene amine oxime injections during seizures provide a "snapshot" of cerebral blood flow that can be imaged by single photon emission computed tomography (SPECT) after seizure termination. Here we show that focal regions of frontal and parietal association cortex show the greatest relative signal increases. Involvement of the higher-order association cortex may explain the profound impairment of consciousness seen in generalized seizures. In addition, focal involvement of the dominant temporal lobe was associated with impaired retrograde verbal memory. Similar focal increases were also seen in imaging of spontaneous secondarily generalized tonic-clonic seizures. Relative sparing of many brain regions during both spontaneous and induced seizures suggests that specific networks may be more important than others in so-called generalized seizures.

Adult↗
PubMed2003

Hypothalamic hamartomas: seven cases and review of the literature.

Hypothalamic hamartomas constitute rare developmental lesions associated with gelastic epilepsy and/or precocious puberty (PP). We elected to review cases encountered at our center (7 patients) and the existing literature (277 patients) to obtain a better understanding of the clinical aspects, pathogenesis, and treatment of this entity. Evidence suggests that gelastic seizures are due to intrinsic epileptogenicity. The cause of the subsequent development of other seizure types, cognitive decline, and diffuse spike-and-wave pattern remains unresolved and is addressed. Anticonvulsants often fail to control seizures and different surgical options are available. Available evidence suggests that a resection through a subtemporal approach is best for lesions that are pedunculated or with a significant prepontine component, while a transcallosal approach is more appropriate for sessile lesions with an intraventricular component. Gamma knife surgery may be especially useful for small sessile lesions, failed partial resections, or patients not appropriate or refusing open surgery.

Adolescent↗
PubMed2003

The multicenter study of epilepsy surgery: recruitment and selection for surgery.

PURPOSE: Multiple studies have examined predictors of seizure outcomes after epilepsy surgery. Most are single-center series with limited sample size. Little information is available about the selection process for surgery and, in particular, the proportion of patients who ultimately have surgery and the characteristics that identify those who do versus those who do not. Such information is necessary for providing the epidemiologic and clinical context in which epilepsy surgery is currently performed in the United States and in other developed countries. METHODS: An observational cohort of 565 surgical candidates was prospectively recruited from June 1996 through January 2001 at six Northeastern and one Midwestern surgical centers. Standardized eligibility criteria and protocol for presurgical evaluations were used at all seven sites. RESULTS: Three hundred ninety-six (70%) study subjects had resective surgery. Clinical factors such as a well-localized magnetic resonance imaging (MRI) abnormality and consistently localized EEG findings were most strongly associated with having surgery. Of those who underwent intracranial monitoring (189, 34%), 85% went on to have surgery. Race/ethnicity and marital status were marginally associated with having surgery. Age, education, and employment status were not. Demographic factors had little influence over the surgical decision. More than half of the patients had intractable epilepsy for >/=10 years and five or more drugs had failed by the time they initiated their surgical evaluation. During the recruitment period, eight new antiepileptic drugs were approved by the Food and Drug Administration for use in the United States and came into increasing use in this study's surgical candidates. Despite the increased availability of new therapeutic options, the proportion that had surgery each year did not fluctuate significantly from year to year. This suggests that, in this group of patients, the new drugs did not provide a substantial therapeutic benefit. CONCLUSIONS: Up to 30% of patients who undergo presurgical evaluations for resective epilepsy surgery ultimately do not have this form of surgery. This is a group whose needs are not currently met by available therapies and procedures. Lack of clear localizing evidence appears to be the main reason for not having surgery. To the extent that these data can address the question, they suggest that repeated attempts to control intractable epilepsy with new drugs will not result in sustained seizure control, and eligible patients will proceed to surgery eventually. This is consistent with recent arguments to consider surgery earlier rather than later in the course of epilepsy. Postsurgical follow-up of this group will permit a detailed analysis of presurgical factors that predict the best and worst seizure outcomes.

Adolescent↗
PubMed2003

Levetiracetam efficacy in refractory partial-onset seizures, especially after failed epilepsy surgery.

PURPOSE: We conducted a retrospective study to evaluate the efficacy of levetiracetam as adjunctive therapy in patients with localization-related epilepsy, and specifically in the subset of patients for whom epilepsy surgery failed. METHODS: Eighty-two patients with uncontrolled partial-onset seizures treated with levetiracetam were identified; epilepsy surgery had failed for 21 (25.6%; group I), and 61 (74.4%) had no prior surgery (group II). Group I and group II patients were comparable in age (mean, 40.7 vs. 41.5 years) and age at seizure onset (mean, 14.4 vs. 18.2 years). Patients who had >/=50% reduction in seizure frequency were considered responders; the remaining patients were considered nonresponders. RESULTS: In patients (group I) for whom surgery had failed, responder rate was 76.1% (16 of 21), including 10 (47.6%) patients who became seizure free. In nonsurgical patients (group II), responder rate was 34.3% (21 of 61), including nine (14.7%) patients who became seizure free. In group I, 11 (91.6%) of 12 temporal resection patients were responders, of whom eight were seizure free; of the remaining nine operated (extratemporal) patients, five (55.5%) were responders, and two were seizure free. In three responders, all in group I, a severe, delayed psychotic syndrome developed 4 to 9 months after levetiracetam introduction, leading to its discontinuation. CONCLUSIONS: These findings suggest that adjunctive levetiracetam therapy should be considered early after failed epilepsy surgery, especially after temporal resection, and may have implications for its use before surgical intervention. Patients should be under close psychiatric observation in this clinical setting.

Adolescent↗
PubMed2003

A retrospective analysis of hippocampal pathology in human temporal lobe epilepsy: evidence for distinctive patient subcategories.

PURPOSE: This study is a retrospective analysis of the pathology of the hippocampus from patients with medically intractable temporal lobe epilepsy. We attempted to relate neuronal density, immunohistochemistry, electrophysiologic data, and surgical outcome. METHODS: Immunostaining patterns for neuropeptide Y, somatostatin, substance P, and dynorphin defined the immunohistochemical characteristics of the hippocampi. Neuronal densities were determined by microscopic cell counts. Sharp electrode recordings from dentate granule cells determined measures of inhibition and excitation. RESULTS: Patient hippocampi without evidence of sclerosis generally resembled autopsy controls on the basis of neuronal densities of hippocampal subfields and patterns of immunostaining. The nonsclerotic hippocampi were divisible into two subgroups on the basis of neuronal density correlations between hippocampal subfields, the excitability of dentate granule cells, etiology, and surgical outcome. Hippocampi with sclerosis were divisible into those with significant neuronal loss confined to area CA1 and those with neuronal loss throughout the hippocampus and dentate gyrus. In the former, the dentate gyrus resembled in morphology the nonsclerotic hippocampi but with slightly increased excitability of the dentate granule cells. The hippocampi with more extensive neuronal loss had changes in immunostaining patterns associated with the dentate gyrus, correlated with significant hyperexcitability of dentate granule cells. The surgical outcome, with the exception of one group, was good in approximately 70-90%. CONCLUSIONS: Hippocampi from patients with intractable temporal lobe epilepsy can be assigned to several groups on the basis of pathophysiology. Different pathologies may represent differing causative mechanisms of intractable temporal lobe epilepsy and be predictive of surgical outcome.

Adult↗
PubMed2003

Surgical management of parietal lobe epilepsy.

Parietal lobe seizure foci are difficult to localize unless there is an MRI lesion or contralateral sensory aura. Rapid network projection often makes scalp EEG and semiology misleading. However, seizure control can be achieved with reasonable success when concordant information guides the physician to a parietal ictal onset. Perhaps the most important messages that this small surgical series provides is that of neurologic outcome. The parietal lobe is a highly convergent cortical region and a major network way station. Except for primary sensory phenomena and language, one cannot temporarily ablate parietal cortical association area within a presumed epileptogenic region and predict the visuospatial, cognitive, and neurologic outcome. Therefore, data demonstrating that one can resect regions of parietal cortex and not cause serious dysfunction are helpful. The mild morbidity encountered in this group of patients would not be necessarily predicted if the same region of normal parietal lobe was resected. Therefore, one must consider cortical plasticity and functional redistribution as possible reasons for this, particularly when most of these substrates are of developmental origin.

Adolescent↗
PubMed2002

When should temporal-lobe epilepsy be treated surgically?

Our current knowledge of mesial-temporal-lobe epilepsy (MTLE) is extensive, yet still insufficient to draw final conclusions on the optimal approach to its therapy. MTLE has been well characterised and can usually be identified with noninvasive studies including scalp electroencephalography (EEG) and video monitoring with ictal recording, magnetic resonance imaging, single-photon-emission computed tomography, positron emission tomography, neuropsychological assessment, and historical and clinical data. Sometimes, invasive EEG is needed to confirm mesial-temporal-lobe seizure onset, which, combined with the underlying pathological abnormality (the substrate) of mesial temporal sclerosis (hippocampal neuronal loss and gliosis), defines MTLE. This disorder is the most common refractory partial epilepsy, and also the one most often treated surgically, because medical treatment fails in 75% of cases, and surgical treatment succeeds in a similar percentage. Despite the recent publication of the first randomised trial of surgical treatment for MTLE, questions remain about the neurological consequences of both medical and surgical treatment, the ultimate gains in quality of life parameters, and the precise predictors of success. Long-term follow-up and analyses of multiple factors in large groups of contemporary patient populations will be necessary to fully answer the question, "is temporal lobe epilepsy a surgical disease?" Right now it should be considered one in most cases.

Anticonvulsants↗
PubMed2002

Interrater reliability among epilepsy centers: multicenter study of epilepsy surgery.

PURPOSE: To measure the interrater reliability of presurgical testing and surgical decisions among epilepsy centers. METHODS: Seven centers participating in an ongoing, prospective multicenter study of resective epilepsy surgery agreed to conform to a detailed protocol regarding presurgical evaluation and surgery. To assess quality assurance, each center independently reviewed 21 randomly selected surgical cases for preoperative study lateralization and localization, and surgical decisions. Interrater reliability was assessed by using intraclass correlation coefficients (ICCs), validated for use with multiple raters, and calculated in a two-way random model based on absolute agreement. RESULTS: Agreement for ICC values: > or = 0.75, excellent; 0.60-0.74, good; 0.40-0.59, fair; < or = 0.39, poor. One center was excluded for missing data. Agreement was excellent for extracranial EEG lateralization (0.8039), magnetic resonance imaging (MRI) lateralization (0.9521) and localization (0.9130), Wada lateralization (0.9453), and intracranial EEG localization (0.7905). Agreement was good for extracranial EEG localization (0.7384) and neuropsychological testing lateralization (0.7178) and localization (0.6891). Consensus about the decision to perform intracranial monitoring was fair (0.5397), in part reflecting one center's tendency toward intracranial monitoring. Overall agreements on whether to perform surgery (0.8311) and specific surgery recommended (0.8164) were excellent. CONCLUSIONS: High interrater reliability among six epilepsy centers was present for interpretation of most components of presurgical testing. Although consensus for the decision to perform intracranial monitoring was only fair, agreements for the ultimate decision about resective surgery and specific choice of resection were excellent. We believe that this study demonstrates the feasibility of implementing multicenter protocols for neurologic management, especially those involving localization, as well as protocols combining study results with clinical decision making.

Electroencephalography↗