An empirically based proposal to identify a short battery to detect neuropsychological impairment in a general adult practice.

Objectives: To demonstrate that 1) models based on small numbers of tests can be statistically developed to identify neuropsychological impairment in a general adult neuropsychology clinic and 2) those models show strong predictive validity on replication in a slightly different sample. Method: Latent Class Analyses (LCA) were used to determine neuropsychological classification in 231 patients referred to general adult neuropsychology services. A clinical rating scale was also used to approximate clinical decision-making. Regression models were constructed in a training sample (n = 127) drawn from an adult neuropsychology clinic using test scores from seven different a priori test battery combinations to predict group membership or clinical rating. The utility of the seven models was assessed in a testing sample (n = 104) from another independent adult neuropsychology clinic. Results: The LCA yielded a two class solution characterized by impaired versus non-impaired performance on neuropsychological tests. A seven test battery provided the best balance of accuracy and length in predicting LCA group with a sensitivity of 84.4% and a specificity of 90%. Sensitivity and specificity were slightly attenuated using the clinical rating scale as the criterion, but the seven test battery still provided good accuracy (AUC=.906). Conclusions: Test protocols based on only five to eight test scores can accurately identify most patients with clinical impairment in a diverse adult neuropsychology clinic. Development of short protocols with adequate sensitivity and specificity will become increasingly important to address long waiting lists in light of the COVID pandemic against the general backdrop of increasing demand for neuropsychological services.

Hope language in patients undergoing epilepsy surgery.

Candidates for epilepsy surgery often use the word "hope" to express their attitudes and beliefs about surgery. However, studies suggest that hope has a multiplicity of meanings that are not well understood. The goal of this analysis was to evaluate whether Candidates for epilepsy surgery use hope language to express a traditional, expected optimism during presurgery interviews. We examined patients' uses of the word "hope" and its derivatives (hoping, hopeful, hopefully) through a secondary analysis of 37 interviews of adult patients prior to epilepsy surgery. Approximately 1/3 of all hope statements were coded as expressions of optimism, while 1/3 were not optimistic, and 1/3 had unclear meanings. In addition to traditionally optimistic uses of the term, other themes surrounding use of this word included ideas of dread, worry, uncertainty, and temporizing language. This information may help clinicians communicate more effectively with patients, enhancing the informed consent process for epilepsy surgery.

Effects of dual pathology on cognitive outcome following left anterior temporal lobectomy for treatment of epilepsy.

The objective of this retrospective study was to determine if dual pathology [DUAL - focal cortical dysplasia (FCD) and mesial temporal sclerosis (MTS)] in patients with left temporal lobe epilepsy is associated with greater risk for cognitive decline following temporal lobectomy than single pathology (MTS only). Sixty-three adults (Mage=36.5years, female: 52.4%) who underwent left anterior temporal lobectomy for treatment of epilepsy (MTS=28; DUAL=35) completed preoperative and postoperative neuropsychological evaluations. The base rate of dual pathology was 55.5%. Repeated measures ANOVAs yielded significant 2-way interactions (group×time) on most measures of language and memory with generally moderate effect sizes. Specifically, patients with MTS only demonstrated postoperative declines, while those with dual pathology remained unchanged or improved. Results suggest that dual pathology may be associated with better cognitive outcome following epilepsy surgery than MTS alone, possibly reflecting limited functionality of the resected tissue or intrahemispheric reorganization of function in the context of a developmental lesion.

Beyond Mere Symptom Relief in Deep Brain Stimulation: An Ethical Obligation for Multi-faceted Assessment of Outcome.

Assessment of outcome following Deep Brain Stimulation (DBS) has traditionally focused on symptom specific and quality of life measures. Greater attention needs to be paid to the diversity of patient goals and values, as well as recognition of the shifting nature of those goals over the course of DBS therapy. We report preliminary data from an empirical study examining patients' goals with respect to DBS in the treatment of Parkinson disease. We argue that a multifaceted assessment of outcome over time, including well validated symptom measures, quality of life, functional and patient specific metrics, is ethically necessary in order to fulfill fiduciary and professional responsibilities. These assessments should be augmented with a deliberative multi-disciplinary process of review and evaluation. Such an approach will lead to improved inform consent, promote better clinical research, and facilitate good patient care by providing a systematic mechanism for capturing and acting on important patient insights. These processes become increasingly critical as DBS begins to be applied to neuropsychiatric disorders.

Role of cortisol in mood and memory in patients with intractable temporal lobe epilepsy.

OBJECTIVE: This study prospectively examined the relationships among late night salivary cortisol (NSC) levels and depressive symptoms, memory performance, and hippocampal volumes in patients with medically intractable temporal lobe epilepsy (TLE) and the potential mediating effects of cortisol in the relationships between these variables. METHODS: Participants included 24 adults with well-characterized medically refractory TLE (right = 11; left = 12; bitemporal = 1). All patients provided saliva samples and completed measures of mood, anxiety, and memory (objective and subjective). MRI-based volumetric analyses of the hippocampi were also conducted. RESULTS: As hypothesized, cortisol was found to be negatively related to several memory measures such that patients with higher cortisol levels demonstrated lower memory performance. However, unexpectedly, cortisol was not related to current symptoms of depression or anxiety, subjective memory ratings, or hippocampal volumes. Consistent with previous findings in the literature, a number of other relationships among the study variables were observed (objective memory and hippocampal volume; subjective memory and mood/anxiety). Results of mediator analyses suggested that cortisol does not mediate the relationship between depression and memory dysfunction or the relationship between depression and hippocampal atrophy. CONCLUSIONS: While cortisol may play a role in memory performance in patients with TLE, it does not fully explain the relationship between depression and mesial temporal dysfunction, likely reflecting the complex and multifactorial relationships among these variables. Results confirm the relationship between memory performance and structural brain integrity and provide further support for a role of depression in subjective memory complaints.

Deep brain stimulation of the ventral internal capsule/ventral striatum for obsessive-compulsive disorder: worldwide experience.

Psychiatric neurosurgery teams in the United States and Europe have studied deep brain stimulation (DBS) of the ventral anterior limb of the internal capsule and adjacent ventral striatum (VC/VS) for severe and highly treatment-resistant obsessive-compulsive disorder. Four groups have collaborated most closely, in small-scale studies, over the past 8 years. First to begin was Leuven/Antwerp, followed by Butler Hospital/Brown Medical School, the Cleveland Clinic and most recently the University of Florida. These centers used comparable patient selection criteria and surgical targeting. Targeting, but not selection, evolved during this period. Here, we present combined long-term results of those studies, which reveal clinically significant symptom reductions and functional improvement in about two-thirds of patients. DBS was well tolerated overall and adverse effects were overwhelmingly transient. Results generally improved for patients implanted more recently, suggesting a 'learning curve' both within and across centers. This is well known from the development of DBS for movement disorders. The main factor accounting for these gains appears to be the refinement of the implantation site. Initially, an anterior-posterior location based on anterior capsulotomy lesions was used. In an attempt to improve results, more posterior sites were investigated resulting in the current target, at the junction of the anterior capsule, anterior commissure and posterior ventral striatum. Clinical results suggest that neural networks relevant to therapeutic improvement might be modulated more effectively at a more posterior target. Taken together, these data show that the procedure can be successfully implemented by dedicated interdisciplinary teams, and support its therapeutic promise.

Impulsivity and risk-taking behavior in focal frontal lobe lesions.

Frontal lobe dysfunction may underlie excessively impulsive and risky behavior observed in a range of neurological disorders. We devised a gambling task to examine these behavior tendencies in a sample of patients who had sustained focal damage to the frontal lobes or nonfrontal cortical regions as well as in a matched sample of healthy control subjects. The main objectives of the study were: (1) to behaviorally dissociate impulsivity and risk-taking; (2) to examine potential associations between specific frontal lesion sites and impulsivity or risk-taking; (3) to investigate the influence of reinforcement and trial timing on both behaviors. Our results indicated that patients and controls were equally likely to perform impulsively. Risk-taking performance strategies, however, were related to left ventrolateral and orbital lesion sites. Moreover, risk-taking was also associated with blunted response alteration following a nonrewarded trial. Patients and control subjects showed identical responses to reward-timing manipulations consistent with formal decision-making theory. These findings suggest that ventrolateral and orbital lesions are related to the reward-based aspects of decision-making (risk-taking) rather than to simple response disinhibition (impulsivity). Reduced reaction to the negative consequences of one's actions may underlie this behavior pattern.

Hippocampal electrical stimulation in mesial temporal lobe epilepsy.

BACKGROUND: Adjustable, reversible therapies are needed for patients with pharmacoresistant epilepsy. Electrical stimulation of the hippocampus has been proposed as a possible treatment for mesial temporal lobe epilepsy (MTLE). METHODS: Four patients with refractory MTLE whose risk to memory contraindicated temporal lobe resection underwent implantation of a chronic stimulating depth electrode along the axis of the left hippocampus. The authors used continuous, subthreshold electrical stimulation (90 microsec, 190 Hz) and a double blind, multiple cross-over, randomized controlled design, consisting of three treatment pairs, each containing two 1-month treatment periods. During each treatment pair the stimulator was randomly turned ON 1 month and OFF 1 month. Outcomes were assessed at monthly intervals in a double blind manner, using standardized instruments and accounting for a washout period. The authors compared outcomes between ON, OFF, and baseline periods. RESULTS: Hippocampal stimulation produced a median reduction in seizures of 15%. All but one patient's seizures improved; however, the results did not reach significance. Effects seemed to carry over into the OFF period, and an implantation effect cannot be ruled out. The authors found no significant differences in other outcomes. There were no adverse effects. One patient has been treated for 4 years and continues to experience substantial long-term seizure improvement. CONCLUSION: The authors demonstrate important beneficial trends, some long-term benefits, and absence of adverse effects of hippocampal electrical stimulation in mesial temporal lobe epilepsy. However, the effect sizes observed were smaller than those reported in non-randomized, unblinded studies.

Does the intracarotid amobarbital procedure predict global amnesia after temporal lobectomy?

PURPOSE: The intracarotid amobarbital procedure (IAP) is widely used to help predict who might be at risk for postoperative amnesia after unilateral temporal lobectomy for intractable seizures. We describe the memory outcome in 10 patients who underwent standard temporal lobectomy, including mesial temporal structures, despite failing the memory portion of the IAP after injections both ipsilateral and contralateral to the resected seizure focus. METHODS: Data for seven of the study subjects were obtained through a retrospective review of patients assessed on a surgical epilepsy unit during a 15-year period who failed the Montreal Neurological Institute IAP memory protocol after both ipsilateral and contralateral injections and subsequently underwent unilateral temporal lobectomy. More recently, we have studied temporal lobectomy patients who failed the Medical College of Georgia memory protocol after both ipsilateral and contralateral injections (n = 3). Preoperative and postoperative memory test scores were compared, and data regarding seizure outcome and self-perception of postoperative memory were collected. RESULTS: At follow-up, none of the patients presented with a pattern indicative of a global amnesia, and 80% demonstrated >90% improvement in their seizure disorder or were seizure-free. CONCLUSIONS: These findings indicate that bilateral memory failure on the IAP does not preclude the removal of an epileptogenic temporal lobe or a successful surgical outcome. In addition, the findings raise questions regarding the validity of the IAP and the possibility that memory may be reorganized in patients with a long history of temporal lobe epilepsy.

Neuropsychological assessment for temporal lobe epilepsy surgery.

Neuropsychological assessment consists of a comprehensive evaluation of cognitive functioning and most often some evaluation of motor skills and sensory status also. Cognitive functions sampled typically include "intelligence" (IQ tests), attention, language skills, visuospatial abilities, "executive skills" and other abilities associated with frontal-lobe function, and learning and memory. Thus, the assessment samples vary widely among a variety of functions, providing a comprehensive picture of an individual's strengths and weaknesses. The resulting pattern points to the probable site of epileptic focus. Neuropsychological findings also serve to predict the risk for postsurgical cognitive decline and, when performance before and after operation is compared, they provide data on the impact of surgery upon cognitive functioning. Comprehensive evaluation of learning and memory is particularly important in this context, because of the frequency of temporal lobe epilepsy and the prominence of memory dysfunction associated with it. In addition, patients slated for elective surgery may also undergo an intracarotid amobarbital procedure (IAP), which is performed to determine the side of cerebral dominance for language and to test the memory capabilities of each hemisphere alone. All of these specialized neuropsychological tools are discussed in this paper.

Cognitive outcome following pallidotomy: the influence of side of surgery and age of patient at disease onset.

OBJECT: The authors studied the neuropsychological correlates of stereotactically guided lesioning of the right and left posteroventral globus pallidus internus (GPi) in a prospective series of patients suffering from Parkinson's disease (PD). METHODS: Eighteen patients with PD who underwent stereotactically guided lesioning of the GPi (left side in 10 patients and right side in eight) completed neuropsychological evaluations before and after surgery. Patients served as their own controls. Multiple two-by-two repeated-measures analyses of variance were used to assess neuropsychological changes as a function of the side in which lesioning was performed (lesioning on the left side compared with that on the right) and surgery (presurgery compared with postsurgery). Relationships between cognitive variables and patient age at disease onset, age at surgery, and disease duration were examined using a linear regression model. The most striking findings were evident from results of a phonemic word fluency test in which patients in whom a left-sided pallidotomy had been performed achieved a mean performance score that was lower than the score of patients in whom a right-sided pallidotomy had been performed; this score declined even more as a result of surgery. Change in performance on the word fluency test across pre- and postoperative assessments was also related to patient age at onset of PD in those who had undergone left-sided pallidotomy, with patients of an older age at disease onset showing the greatest decline in performance. CONCLUSIONS: These preliminary findings indicate that the side on which surgery was performed and patient age at onset of PD are important in the prediction of postoperative cognitive outcome. The findings also indicate that stereotactically guided lesioning of the GPi presents a relatively mild cognitive risk.

MR in temporal lobe epilepsy: analysis with pathologic confirmation.

PURPOSE: We evaluated the MR findings in patients with temporal lobe epilepsy to determine the predictive value of MR imaging in assessing patient outcome. METHODS: MR studies from 186 of 274 consecutive patients who underwent temporal lobectomy for intractable epilepsy were reviewed retrospectively. Images were interpreted by an experienced neuroradiologist, who was blinded to the side of seizure activity and to pathologic findings. RESULTS: MR imaging exhibited 93% sensitivity and 83% specificity in detecting hippocampal/amygdalar abnormalities (n = 121), and 97% sensitivity and 97% specificity in detecting abnormalities in the rest of the temporal lobe (n = 60). Abnormal high signal of the hippocampus on T2-weighted images had a sensitivity of 93% and specificity of 74% in predicting mesial temporal sclerosis (n = 115). The presence of hippocampal atrophy on MR correlated with the duration of seizures. Sensitivity and specificity of MR imaging in detecting temporal lobe tumors (n = 42) were 83% and 97%, respectively, based on abnormal signal and mass effect. After surgery, 63% of patients were seizure free and 28% had a significant reduction of seizure frequency at an average of 24 months (range, 12 to 78 months) after surgery. Patients with a single lesion in the anterior temporal lobe or hippocampus/amygdala had a better outcome than patients with multiple lesions (n = 22). Interrater agreement varied from 0.4 to 0.93, with best agreement for tumors or abnormal hippocampal signal on T2-weighted images. CONCLUSION: MR imaging is highly sensitive in detecting and locating abnormalities in the temporal lobe and the hippocampus/amygdala in patients with temporal lobe epilepsy. Hippocampal atrophy appears to correspond to the duration of seizure disorder.

Propofol sedation during awake craniotomy for seizures: patient-controlled administration versus neurolept analgesia.

This prospective study evaluated the safety and efficacy of patient-controlled sedation (PCS) using propofol during awake seizure surgery performed under bupivacaine scalp blocks. Thirty-seven patients were randomized to receive either propofol PCS combined with a basal infusion of propofol (n = 20) or neurolept analgesia using an initial bolus dose of fentanyl and droperidol followed by a fentanyl infusion (n = 17). Both groups received supplemental fentanyl and dimenhydrinate for intraoperative pain and nausea, respectively. Comparisons were made between groups for sedation, memory, and cognitive function, patient satisfaction, and incidence of complications. Levels of intraoperative sedation and patient satisfaction were similar between groups. Memory and cognitive function were well preserved in both groups. The incidence of transient episodes of ventilatory rate depression (<8 bpm) was more frequent among the propofol patients (5 vs 0, P = 0.04), particularly after supplemental doses of opioid. Intraoperative seizures were more common among the neurolept patients (7 vs 0, P = 0.002). PCS using propofol represents an effective alternative to neurolept analgesia during awake seizure surgery performed in a monitored care environment.

Prospective neuropsychological assessment of nondemented patients with biopsy proven senile plaques.

Senile plaques are characteristic of Alzheimer's disease but also occur as an age-related change in some neurologically normal individuals at autopsy. The significance of these "incidental" senile plaques, with regard to the development of dementia, is unknown and cannot be assessed by postmortem studies. Patients with biopsy proven senile plaques offer an important opportunity for prospective followup. We identified senile plaques in temporal lobectomy specimens, removed in the surgical treatment of intractable epilepsy, from 11 patients. Review of preoperative neuropsychological test results showed no suggestion of dementia in any of the patients with senile plaques and no significant difference compared with controls. Postoperative followup ranged from 2 to 7 years (mean, 3.7 yr). There was no evidence of generalized cognitive deterioration in any of the study patients. These findings indicate that an abundance of senile plaques may be present without associated dementia and without cognitive deterioration for at least several years.

Characteristics and mechanisms of epilepsy spectrum disorder: an explanatory model.

Recently, a complex neurobehavioral disorder with paroxysmal affective, psychosensory, and cognitive symptoms has been described by a number of different neuropsychiatric and neuropsychological practitioners. Although a variety of different terms have been used to characterize this clinical entity, the recently coined term epilepsy spectrum disorder (ESD) will be used for the purposes of this article. The clinical identification, neuropsychological characteristics, differential diagnosis, etiology, and treatment response of such patients will be reviewed. The possible neuropathological and neurophysiological mechanisms underlying ESD and implications for future research will also be discussed It is argued that neuropsychologists should be more familiar with this syndrome because such patients are frequently referred for neuropsychological assessment when practitioners from medical disciplines are confused by the atypical and polysymptomatic clinical presentations of ESD patients.

Neuropsychologic dysfunction in women following leuprolide acetate induction of hypoestrogenism.

OBJECTIVE: The study investigated the neuropsychological status of women with induced hypoestrogenism. DESIGN: An ABA design was employed in which neuropsychological measures were repeated prior to, during, and after induction of hypoestrogenism with leuprolide acetate. SETTING: The study took place in a medical school affiliated in vitro fertilization clinic. INTERVENTIONS: Leuprolide acetate was administered to all subjects as part of in vitro fertilization. METHODS: Eighteen women receiving in vitro fertilization treatment underwent neuropsychological testing before, during, and after treatment with leuprolide acetate and gonadotrophins. The neuropsychological test battery was selected on the basis of previous patients' symptomatic complaints during periods of hypoestrogenism with leuprolide acetate. RESULTS: Depending upon the tests administered, some individuals showed significant cognitive deficits during therapy particularly in the areas of memory, fine motor coordination, and two-point discrimination. Two of the 18 subjects showed very substantial neuropsychological sequelae including memory gaps and disturbances in a variety of neuropsychological test performances. However, in terms of group statistics, only two-point discrimination and delayed recall memory test performance proved significant. Not all measures were sensitive for the group, as many tests displayed a balance between individuals who showed practice effects and those who showed detrimental effects. CONCLUSIONS: For a substantial portion of individuals, hypoestrogenism can result in statistically significant or clinically noteworthy problems with memory, dexterity, and two-point discrimination.