Long-Term Efficacy of Posterior Neurectomy in Anterior Cutaneous Nerve Entrapment Syndrome.

Objective: To analyze long-term treatment outcomes of a posterior neurectomy in a large cohort of patients with anterior cutaneous nerve entrapment syndrome (ACNES). Summary Background Data: The current step-up treatment approach for ACNES involves abdominal wall tender point injections, pulsed radiofrequency, and neurectomy. If an anterior neurectomy fails or pain reoccurs, a posterior neurectomy is considered as a final surgical option. Data on posterior neurectomy treatment outcomes are scarce. Methods: ACNES patients who underwent a unilateral posterior neurectomy between 2012 and 2022 in a single institution completed a questionnaire regarding their current pain status. Primary outcomes were short- and long-term treatment success, defined as ≥50% pain relief. Patients were stratified whether the operative indication was recurrent pain (>3 months) after an initially successful anterior neurectomy or ongoing pain after an anterior neurectomy. Results: Data from 260 of 379 patients (77% female, mean age 42 years) were analyzed (68.6% response rate). Sensitivity analysis found that short-term outcomes were similar between responders and non-responders. The recurrent pain group demonstrated significantly better treatment outcomes compared to the ongoing pain group, both in the short-term (7 weeks; treatment success 79.2% vs. 53.2%, p < 0.001) and long-term (58 months; treatment success 61.1% vs. 42.0%, p = 0.001). Sixteen (minor) complications (6.2%) were reported, resulting in three surgical re-interventions (1.2%). Conclusion: A posterior neurectomy is long-term beneficial in approximately half of patients although treatment success is better for recurrent pain than ongoing pain. These findings aid in optimizing preoperative patient counseling.

A positive scratch collapse test in anterior cutaneous nerve entrapment syndrome indicates its neuropathic character.

OBJECTIVES: Chronic abdominal pain is occasionally caused by an abdominal wall entity such as anterior cutaneous nerve entrapment syndrome (ACNES). This syndrome is thought to occur due to intercostal nerve branches (T7-12) that are entrapped in the rectus abdominis muscles. The diagnosis is largely based on subjective clues in patient history and physical examination. A test referred to as the scratch collapse test (SCT) is used as an additional diagnostic tool in peripheral nerve entrapment syndromes such as the carpal tunnel syndrome. The aim of the present study is to investigate whether an SCT was positive in patients with suspected ACNES. If so, this finding may support its hypothesized neuropathic character. METHODS: A prospective, case-control study was performed among patients with ACNES (n = 20) and two control groups without ACNES (acute intra-abdominal pathology n = 20; healthy n = 20), all were consecutively included. ACNES was diagnosed based on previously published criteria. The SCT test was executed at the painful abdominal area in both patient groups and at a corresponding area in healthy controls. Predictive values, sensitivity, and specificity were calculated. Videos of tests were evaluated by blinded observers. RESULTS: SCT was judged positive in 19 of 20 ACNES patients but not in any of the 40 controls. A 95% sensitivity (confidence interval [CI]: 75-99) and optimal specificity (100%; CI: 83-100) were calculated. CONCLUSIONS: The positive SCT supports the hypothesis that ACNES is an entrapment neuropathy. A positive SCT should be considered a major diagnostic criterion for ACNES.

Neuropsychological characteristics of drug resistant epilepsy patients with and without comorbid functional seizures.

INTRODUCTION: Neuropsychological testing is a mandatory component in the evaluation of drug resistant epilepsy. The results of testing may assist with both the localization of an epilepsy as well as assessment of surgical risk. Previous studies have demonstrated differences in the neuropsychological performance of patients with epilepsy and functional seizures. We hypothesized that comorbid functional seizures could potentially influence neuropsychological test performance. Therefore, we evaluated whether there is a difference in the neuropsychological test results between drug resistant epilepsy patients with and without comorbid functional seizures. METHOD: Neuropsychological test results were compared between 25 patients with drug resistant focal epilepsy and 25 patients that also had documented functional seizures. Univariate analyses and multiple logistic regression models were used to both assess performance differences between the groups and to assess whether test results could be used to accurately identify which patients had comorbid functional seizures. RESULTS: Epilepsy patients with comorbid functional seizures performed significantly worse on the FAS Verbal Fluency Test compared to ES patients (p = 0.047). Digit Span Backwards (p = 0.10), Digit Span Forwards (p = 0.14) and Working Memory Index (p = 0.10) tended to be lower in the epilepsy and functional seizures group but was not statistically significant. A multiple logistic regression model using the results of four neuropsychological tests was able to identify patients with comorbid functional seizures with 83.33% accuracy. CONCLUSIONS: There are appeared to be some differences in the neuropsychological performance among drug resistant epilepsy patients based on whether they have comorbid functional seizures. These findings may have relevant implications for the interpretation of neuropsychological test results.

Visceral symptoms in patients with anterior cutaneous nerve entrapment syndrome (ACNES): expression of viscerosomatic reflexes?

PURPOSE: Anterior cutaneous nerve entrapment (ACNES) is characterized by neuropathic pain in a predictable, circumscript abdominal area. The diagnostic delay is long, with half of ACNES-affected individuals reporting nausea, bloating, or loss of appetite mimicking visceral disease. The aim of this study was to describe these phenomena and to determine whether treatment could successfully reverse the visceral symptoms. METHODS: This prospective observational study was conducted between July 2017 and December 2020 at SolviMáx, Center of Excellence for Chronic Abdominal Wall and Groin Pain, Máxima Medical Center, Eindhoven. Adult patients who fulfilled published criteria for ACNES and reported at least one visceral symptom at intake were eligible for the study. A self-developed Visceral Complaints ACNES Score (VICAS) questionnaire that scores several visceral symptoms (minimum 1 point, maximum 9 points) was completed before and after therapy. The success of treatment was defined as at least 50% reduction in pain. RESULTS: Data from 100 selected patients (86 females) aged 39 ± 5 years were available for analysis. Frequently reported symptoms were abdominal bloating (78%), nausea (66%) and altered defecation (50%). Successful treatment significantly reduced the number of visceral symptoms, with a VICAS before of 3 (range 1-8) and after of 1 (range 0-6) (p < 0.001). A low baseline VICAS was associated with successful treatment outcome (OR 0.738, 95% CI 0.546-0.999). CONCLUSION: Patients with ACNES may report a variety of visceral symptoms. Successful treatment substantially reduces these visceral symptoms in selected patients.

The Scratch Collapse Test in patients diagnosed with Anterior Cutaneous Nerve Entrapment Syndrome (ACNES): A report of three cases.

INTRODUCTION AND IMPORTANCE: The Scratch Collapse Test (SCT) is currently used as a supportive tool diagnosing peripheral nerve neuropathies including carpal tunnel syndrome or peroneal nerve entrapment. Some patients with chronic abdominal pain suffer from entrapment of terminal branches of intercostal nerves (anterior cutaneous nerve entrapment syndrome, ACNES). ACNES is characterized by a severe disabling pain at a predictable area of the anterior abdomen. Clinical examination shows altered skin sensation and painful pinching at the area of pain. However, these findings may be subjective. CASE PRESENTATION: In three female patients aged 71, 33, and 43 years with suspected ACNES, the SCT was positive when scratching over the skin of the affected nerve-ending at the abdominal wall. The diagnosis ACNES was confirmed with a local abdominal wall infiltration at the tenderpoint in all three patients. In case three, the SCT turned negative after lidocaine infiltration. CLINICAL DISCUSSION: ACNES was hitherto a clinical diagnosis just based on clues in medical history and physical examination. Performing a SCT in patients possibly having ACNES may additionally contribute to the diagnosis. CONCLUSION: The SCT may serve as an additional tool for diagnosing patients with possible ACNES. A positive SCT in patients with ACNES supports the hypothesis that ACNES is indeed a peripheral neuropathy of terminal branches of the lower thoracic intercostal nerves. Controlled research is necessary to confirm the role of a SCT in ACNES.

Epilepsy with anterior temporal encephaloceles: Baseline characteristics, post-surgical outcomes, and comparison to mesial temporal sclerosis.

OBJECTIVE: To review clinical and neuropsychological characteristics and natural history of a series of patients with temporal lobe epilepsy (TLE) and anterior temporal encephaloceles (ATE) and compare them to a similar series of TLE patients with mesial temporal sclerosis (MTS) to identify characteristics suggestive of ATE-related epilepsy. METHODS: Patients with epilepsy and ATE were identified via clinic encounters and consensus epilepsy surgery conference at a Level 4 epilepsy center. The drug-resistant subset of these patients who underwent epilepsy surgery (twenty-two of thirty-five) were compared to age- and laterality-matched patients with MTS. Clinical, neuropsychological, electrophysiologic, and surgical data were abstracted through chart review. RESULTS: In comparison with MTS, ATE patients were more often female, had significantly later onset of epilepsy, and did not have prior febrile seizures. In addition, ATE patients were more likely to have chronic headaches and other historical features consistent with idiopathic intracranial hypertension (IIH). Failure to identify ATE on initial imaging was common. Most patients had limited temporal cortical resections sparing mesial structures. Of the twenty ATE patients who had a long-term postsurgical follow-up, seventeen (85%) had International League Against Epilepsy (ILAE) Class 1 or 2 outcomes. SIGNIFICANCE: A shorter duration of epilepsy, female gender, and lack of history of febrile seizures may suggest ATE as an etiology of refractory TLE in adults. Targeted encephalocele resections can result in seizure freedom, underscoring the importance of encephalocele identification.

Albumin Glycation Affects the Delivery of C-Peptide to the Red Blood Cells.

Serum albumin is a prominent plasma protein that becomes modified in hyperglycemic conditions. In a process known as glycation, these modifications can change the structure and function of proteins, which decrease ligand binding capabilities and alter the bioavailability of ligands. C-peptide is a molecule that binds to the red blood cell (RBC) and stimulates the release of adenosine triphosphate (ATP), which is known to participate in the regulation of blood flow. C-peptide binding to the RBC only occurs in the presence of albumin, and downstream signaling cascades only occur when the albumin and C-peptide complex contains Zn2+. Here, we measure the binding of glycated bovine serum albumin (gBSA) to the RBC in conditions with or without C-peptide and Zn2+. Key to these studies is the analytical sample preparation involving separation of BSA fractions with boronate affinity chromatography and characterization of the varying glycation levels with mass spectrometry. Results from this study show an increase in binding for higher % glycation of gBSA to the RBCs, but a decrease in ability to deliver C-peptide (0.75 ± 0.11 nM for 22% gBSA) compared to samples with less glycation (1.22 ± 0.16 nM for 13% gBSA). A similar trend was measured for Zn2+ delivery to the RBC as a function of glycation percentage. When 15% gBSA or 18% gBSA was combined with C-peptide/Zn2+, the derived ATP release from the RBCs significantly increased to 113% or 36%, respectively. However, 26% gBSA with C-peptide/Zn2+ had no significant increase in ATP release from RBCs. These results indicate that glycation of BSA interferes in C-peptide and Zn2+ binding to the RBC and subsequent RBC ATP release, which may have implications in C-peptide therapy for people with type 1 diabetes.

Prediction of Naming Outcome With fMRI Language Lateralization in Left Temporal Epilepsy Surgery.

BACKGROUND AND OBJECTIVES: Naming decline after left temporal lobe epilepsy (TLE) surgery is common and difficult to predict. Preoperative language fMRI may predict naming decline, but this application is still lacking evidence. We performed a large multicenter cohort study of the effectiveness of fMRI in predicting naming deficits after left TLE surgery. METHODS: At 10 US epilepsy centers, 81 patients with left TLE were prospectively recruited and given the Boston Naming Test (BNT) before and ≈7 months after anterior temporal lobectomy. An fMRI language laterality index (LI) was measured with an auditory semantic decision-tone decision task contrast. Correlations and a multiple regression model were built with a priori chosen predictors. RESULTS: Naming decline occurred in 56% of patients and correlated with fMRI LI (r = -0.41, p < 0.001), age at epilepsy onset (r = -0.30, p = 0.006), age at surgery (r = -0.23, p = 0.039), and years of education (r = 0.24, p = 0.032). Preoperative BNT score and duration of epilepsy were not correlated with naming decline. The regression model explained 31% of the variance, with fMRI contributing 14%, with a 96% sensitivity and 44% specificity for predicting meaningful naming decline. Cross-validation resulted in an average prediction error of 6 points. DISCUSSION: An fMRI-based regression model predicted naming outcome after left TLE surgery in a large, prospective multicenter sample, with fMRI as the strongest predictor. These results provide evidence supporting the use of preoperative language fMRI to predict language outcome in patients undergoing left TLE surgery. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that fMRI language lateralization can help in predicting naming decline after left TLE surgery.

Ultrasound-guided abdominal wall infiltration versus freehand technique in anterior cutaneous nerve entrapment syndrome (ACNES): randomized clinical trial.

BACKGROUND: The optimal technique of abdominal wall infiltration for chronic abdominal wall pain due to anterior cutaneous nerve entrapment syndrome (ACNES) is unknown. The aim of this study was to compare pain reduction after an abdominal wall anaesthetic injection by use of an ultrasound-guided technique (US) or given freehand (FH). METHODS: In this multicentre non-blinded randomized trial, adult patients with ACNES were randomized (1:1) to an US or a FH injection technique. Primary outcome was the proportion of injections achieving a minimum of 50 per cent pain reduction on the Numeric Rating Scale (range 0-10) 15-20 min after abdominal wall infiltration ('successful response'). Secondary outcomes were treatment efficacy after 6 weeks and 3 months, and the influence of the subcutaneous tissue thickness on treatment outcome. RESULTS: Between January 2018 and April 2020, 391 injections (US = 192, FH = 199) were administered in 117 randomized patients (US = 55, FH = 62; 76.0 per cent female, mean age 45 years). The proportion of successful responses did not significantly differ immediately after the injection regimen (US 27.1 per cent versus FH 33.2 per cent; P = 0.19) or after 3 months (US 29.4 per cent versus FH 30.5 per cent; P = 0.90). Success was not determined by subcutaneous tissue thickness. CONCLUSION: Pain relief following abdominal wall infiltration by a US or FH technique in ACNES is similar and not influenced by subcutaneous tissue thickness. REGISTRATION NUMBER: Dutch Clinical Trial Register NL8465.

Persistent pain relief following a single injection of a local anesthetic for neuropathic abdominal wall and groin pain.

OBJECTIVES: It is our experience that a small portion of patients with neuropathic abdominal wall pain syndromes such as the anterior cutaneous nerve entrapment syndrome (ACNES) have a long term beneficial response following just one single tender point injection (TPI) with a local anesthetic agent. This report focuses on the phenomenon of ongoing pain relief following a single local anesthetic injection in neuropathic abdominal wall and groin pain syndromes. METHODS: This report is an overview based on earlier studies from a center of expertise for neuropathic abdominal wall and groin pain syndromes. All studies on neuropathic abdominal wall and groin pain syndromes reporting on efficacy of a diagnostic TPI using a local anesthetic agent were included. RESULTS: A total of 10 studies including 834 patients fulfilled study criteria. Each of these 10 studies found that approximately 10% (range, 4-25%) of the cases experienced persistent pain relief after a single TPI with lidocaine 1%. CONCLUSIONS: Persistent pain relief after a single TPI using a local anesthetic agent may be observed in approximately one of 10 patients suffering from neuropathic abdominal wall or groin pain syndromes. When a patient is suspected of having a neuropathic abdominal wall or groin pain syndrome, a single TPI using a local anesthetic agent should be administered as long term pain relief may occasionally occur.

Resting-state hippocampal networks related to language processing reveal unique patterns in temporal lobe epilepsy.

OBJECTIVE: Patients with temporal lobe epilepsy (TLE) commonly experience a broad range of language impairments. These deficits are thought to arise from repeated seizure activity that damages language regions. However, connectivity between the seizure onset region in the hippocampus and regions related to language processing has rarely been studied, and could also have a strong impact on language function. The purpose of this study was to use resting-state functional connectivity (FC) measures to assess hippocampal network patterns and their relation to language abilities in patients with right TLE (RLTE), left TLE (LTLE), and healthy controls. METHODS: Presurgical resting-state 3T functional MRI data were acquired from 40 patients with mesial TLE (27 RTLE, 13 LTLE) and 54 controls. The regions of interest were the anterior and posterior bilateral hippocampi and eleven regions grouped by frontal or temporo-parietal locations, including large areas of language-related cortex. FC values were computed with the right/left anterior and posterior hippocampi as the seeds and frontal and temporo-parietal regions as targets. Resting-state lateralization indices were also calculated (LI-Rest), and all FC measures were correlated to neuropsychological language scores and measures related to manifestation of epilepsy including age of onset, duration of disease, monthly seizure frequency, and hippocampal volume. RESULTS: We found significant group differences between the anterior hippocampi and temporo-parietal regions closest to the seizure focus, in which RTLE and LTLE showed stronger connectivity to their contralateral hippocampus, while controls showed similar connectivity to both hippocampi. In addition, LI-Rest demonstrated significantly more right lateralization in LTLE compared to RTLE for temporo-parietal regions only. In LTLE, we found significant associations between stronger hippocampal network resting-state FC and later age of onset and decreased left anterior hippocampal volume. SIGNIFICANCE: The results of our study indicate that the presence of TLE impacts hippocampal-temporo-parietal networks relevant to language processing.

Baseline neuropsychological characteristics in patients with epilepsy with left temporal lobe encephaloceles compared with left mesial temporal sclerosis.

BACKGROUND: Temporal lobe encephaloceles (TE) are increasingly recognized as a cause of drug-resistant temporal lobe epilepsy. Improved recognition of these lesions offers an opportunity to treat them with a limited resection sparing the hippocampus. However, as they can be difficult to identify on imaging, additional clues pointing to the diagnosis can be helpful. We sought to understand the baseline cognitive/neuropsychological profile in patients with left temporal lobe epilepsy caused by encephaloceles compared with that caused by mesial temporal sclerosis (MTS), a common entity in the differential diagnosis. METHODS: Neuropsychological testing, including language (semantic and phonemic fluency and naming), verbal memory, intelligence quotient (IQ), and executive function measures were compared across two groups (five patients with left TE and five age- and gender-matched patients with left MTS). Other clinical variables related to cognition, including patient age, electroencephalographic characteristics, epilepsy duration, and factors related to antiseizure medication dosing, were also compared between groups. RESULTS: More patients with left MTS had atypical language lateralization (3/5 with right-sided language in the group with MTS compared with 0/5 in the group with TE). Patients with MTS had significantly worse scores on the Verbal Comprehension Index (VCI) subscore of the Wechsler Adult Intelligence Scale (WAIS; p = 0.026). General IQ was also worse in patients with MTS (p = 0.028). There was a trend towards worse executive function in patients with MTS as measured on Trails B (p = 0.096). Other measures related to language and verbal memory did not differ significantly between the groups nor did other relevant clinical variables, except epilepsy duration, which was significantly longer in patients with MTS (p = 0.0001). CONCLUSIONS: This pilot study demonstrates few significant differences between the groups with left MTS and TE surveyed. A higher rate of atypical language lateralization was noted in patients with left MTS. The higher baseline global IQ and VCI scores in patients with left TE compared with patients with MTS may be attributable to longer duration of epilepsy in patients with left MTS. Future work with a larger sample size will focus on establishing a unique neuropsychological profile related to epilepsy due to TE.

Temporal lobe regions essential for preserved picture naming after left temporal epilepsy surgery.

OBJECTIVE: To define left temporal lobe regions where surgical resection produces a persistent postoperative decline in naming visual objects. METHODS: Pre- and postoperative brain magnetic resonance imaging data and picture naming (Boston Naming Test) scores were obtained prospectively from 59 people with drug-resistant left temporal lobe epilepsy. All patients had left hemisphere language dominance at baseline and underwent surgical resection or ablation in the left temporal lobe. Postoperative naming assessment occurred approximately 7 months after surgery. Surgical lesions were mapped to a standard template, and the relationship between presence or absence of a lesion and the degree of naming decline was tested at each template voxel while controlling for effects of overall lesion size. RESULTS: Patients declined by an average of 15% in their naming score, with wide variation across individuals. Decline was significantly related to damage in a cluster of voxels in the ventral temporal lobe, located mainly in the fusiform gyrus approximately 4-6 cm posterior to the temporal tip. Extent of damage to this region explained roughly 50% of the variance in outcome. Picture naming decline was not related to hippocampal or temporal pole damage. SIGNIFICANCE: The results provide the first statistical map relating lesion location in left temporal lobe epilepsy surgery to picture naming decline, and they support previous observations of transient naming deficits from electrical stimulation in the basal temporal cortex. The critical lesion is relatively posterior and could be avoided in many patients undergoing left temporal lobe surgery for intractable epilepsy.

A novel 3D-printed centrifugal ultrafiltration method reveals in vivo glycation of human serum albumin decreases its binding affinity for zinc.

Plasma proteins are covalently modified in vivo by the high-glucose conditions in the bloodstreams of people with diabetes, resulting in changes to both structure and function. Human Serum Albumin (HSA) functions as a carrier-protein in the bloodstream, binding various ligands and tightly regulating their bioavailability. HSA is known to react with glucose via the Maillard reaction, causing adverse effects on its ability to bind and deliver certain ligands, such as metals. Here, the binding between in vivo glycated HSA and zinc (Zn2+) was determined using a novel centrifugal ultrafiltration method that was developed using a 3D-printed device. This method is rapid (90 minutes), capable of high-throughput measurements (24 samples), low-cost (<$1.00 USD per device) and requires lower sample volumes (200 µL) compared to other binding techniques. This device was used to determine an equilibrium dissociation constant between Zn2+ and a commercially obtained normal HSA (nHSA) with a glycation level of 11.5% (Kd = 2.1 (±0.5) × 10-7 M). A glycated fraction of the nHSA sample was enriched (gHSA, 65.5%) and isolated using boronate-affinity chromatography, and found to have a 2.3-fold decrease in Zn2+ binding-affinity (Kd = 4.8 (±0.8) × 10-7 M) when compared to the nHSA sample. The level of glycation of HSA in control plasma (13.0% ± 0.8, n = 3 donors) and plasma from people with diabetes (26.9% ± 6.6, n = 5 donors) was assessed using mass spectrometry. Furthermore, HSA was isolated from plasma obtained in-house from a person with type 1 diabetes and found to have a glycation level of 24.1% and Kd = 3.3 (± 0.5) × 10-7 M for Zn2+, revealing a 1.5-fold decrease in binding affinity compared to nHSA. These findings suggest that increased levels of glycated HSA result in reduced binding to Zn2+, which may have implications in complications associated with diabetes.

Chronic Abdominal Pain After Previous Bariatric Surgery: Consider the Abdominal Wall.

BACKGROUND: Up to 30% of patients who undergo bariatric surgery experience recurrent abdominal pain within 3 years after the operation. Although some causes for persisting discomfort are well known, a small portion of patients may suffer from an abdominal wall pain associated with Anterior Cutaneous Nerve Entrapment Syndrome (ACNES). Aim of the present study is to discuss incidence, clinical presentation, and treatment outcome in patients with ACNES after bariatric surgery. METHODS: This retrospective observational cohort study analyzed electronically stored data of patients with ACNES having a history of bariatric surgery. All were treated for ACNES between 2011 and 2017 in a Dutch center of excellence for abdominal wall and groin pain. Success after treatment was defined as a minimal 50% drop in pain level using a Numeric Rating Scale. RESULTS: A total of 49 patients (female n = 44, median age 45 (25-63) years) were identified. Four (8%) experienced long-term pain relief after just one abdominal wall infiltration with lidocaine. Ten additional patients reported success after 2-5 injections. A total of 35 unresponsive patients chose to undergo a neurectomy that was successful in 27. Therefore, this step-up approach conferred an 84% success rate. Occurrence of ACNES after bariatric surgery was estimated at 1 in 100 patients. CONCLUSION: ACNES should be considered in the differential diagnosis of ongoing pain following previous bariatric surgery. A treatment regimen including abdominal wall infiltrations using an anesthetic agent or a neurectomy is successful in a vast majority of these patients.

Changes in description naming for common and proper nouns after left anterior temporal lobectomy.

Numerous studies have shown that surgical resection of the left anterior temporal lobe (ATL) is associated with a decline in object naming ability (Hermann et al., 1999). In contrast, few studies have examined the effects of left ATL surgery on auditory description naming (ADN) or category-specific naming. Compared with object naming, which loads heavily on visual recognition processes, ADN provides a more specific measure of concept retrieval. The present study examined ADN declines in a large group of patients who were tested before and after left ATL surgery, using a 2 × 2 × 2 factorial manipulation of uniqueness (common vs. proper nouns), taxonomic category (living vs. nonliving things), and time (pre- vs. postsurgery). Significant declines occurred across all categories but were substantially larger for proper living (PL) concepts, i.e., famous individuals. The disproportionate decline in PL noun naming relative to other conditions is consistent with the notion that the left ATL is specialized not only for retrieval of unique entity concepts, but also plays a role in processing social concepts and person-specific features.

Brainstem Functional Connectivity Disturbances in Epilepsy may Recover After Successful Surgery.

BACKGROUND: Focal seizures in temporal lobe epilepsy (TLE) are associated with widespread brain network perturbations and neurocognitive problems. OBJECTIVE: To determine whether brainstem connectivity disturbances improve with successful epilepsy surgery, as recent work has demonstrated decreased brainstem connectivity in TLE that is related to disease severity and neurocognitive profile. METHODS: We evaluated 15 adult TLE patients before and after (>1 yr; mean, 3.4 yr) surgery, and 15 matched control subjects using magnetic resonance imaging to measure functional and structural connectivity of ascending reticular activating system (ARAS) structures, including cuneiform/subcuneiform nuclei (CSC), pedunculopontine nucleus (PPN), and ventral tegmental area (VTA). RESULTS: TLE patients who achieved long-term postoperative seizure freedom (10 of 15) demonstrated increases in functional connectivity between ARAS structures and fronto-parietal-insular neocortex compared to preoperative baseline (P = .01, Kruskal-Wallis), with postoperative connectivity patterns resembling controls' connectivity. No functional connectivity changes were detected in 5 patients with persistent seizures after surgery (P = .9, Kruskal-Wallis). Among seizure-free postoperative patients, larger increases in CSC, PPN, and VTA functional connectivity were observed in individuals with more frequent seizures before surgery (P < .05 for each, Spearman's rho). Larger postoperative increases in PPN functional connectivity were seen in patients with lower baseline verbal IQ (P = .03, Spearman's rho) or verbal memory (P = .04, Mann-Whitney U). No changes in ARAS structural connectivity were detected after successful surgery. CONCLUSION: ARAS functional connectivity disturbances are present in TLE but may recover after successful epilepsy surgery. Larger increases in postoperative connectivity may be seen in individuals with more severe disease at baseline.

Unsolicited Patient Complaints Identify Physicians with Evidence of Neurocognitive Disorders.

OBJECTIVES: Determine whether words contained in unsolicited patient complaints differentiate physicians with and without neurocognitive disorders (NCD). METHODS: We conducted a nested case-control study using data from 144 healthcare organizations that participate in the Patient Advocacy Reporting System program. Cases (physicians with probable or possible NCD) and two comparison groups of 60 physicians each (matched for age/sex and site/number of unsolicited patient complaints) were identified from 33,814 physicians practicing at study sites. We compared the frequency of words in patient complaints related to an NCD diagnostic domain between cases and our two comparison groups. RESULTS: Individual words were all statistically more likely to appear in patient complaints for cases (73% of cases had at least one such word) compared to age/sex matched (8%, p < 0.001 using Pearson's χ2 test, χ2 = 30.21, df = 1) and site/complaint matched comparisons (18%, p < 0.001 using Pearson's χ2 test, χ2 = 17.51, df = 1). Cases were significantly more likely to have at least one complaint with any word describing NCD than the two comparison groups combined (conditional logistic model adjusted odds ratio 20.0 [95% confidence interval 4.9-81.7]). CONCLUSIONS: Analysis of words in unsolicited patient complaints found that descriptions of interactions with physicians with NCD were significantly more likely to include words from one of the diagnostic domains for NCD than were two different comparison groups. Further research is needed to understand whether patients might provide information for healthcare organizations interested in identifying professionals with evidence of cognitive impairment.

Relating structural and functional brainstem connectivity to disease measures in epilepsy.

OBJECTIVE: While epilepsy studies rarely examine brainstem, we sought to examine the hypothesis that temporal lobe epilepsy (TLE) leads to subcortical arousal center dysfunction, contributing to neocortical connectivity and neurocognitive disturbances. METHODS: In this case-control study of 26 adult patients with TLE and 26 controls, we used MRI to measure structural and functional connectivity of the cuneiform/subcuneiform nuclei (CSC), pedunculopontine nucleus, and ventral tegmental area. Ascending reticular activating system connectivity patterns were related to neuropsychological and disease measures. RESULTS: Compared to controls, patients with TLE demonstrated reductions in ascending reticular activating system structural and functional connectivity, most prominently to neocortical regions (p < 0.05, unpaired t tests, corrected). While reduced CSC structural connectivity was related to impaired performance IQ and visuospatial memory, diminished CSC functional connectivity was associated with impaired verbal IQ and language abilities (p < 0.05, Spearman ρ, t tests). Finally, CSC structural connectivity decreases were quantitatively associated with consciousness-impairing seizure frequency (p < 0.05, Spearman ρ) and the presence of generalized seizures (p < 0.05, unpaired t test), suggesting a relationship to disease severity. CONCLUSIONS: Connectivity perturbations in brainstem arousal centers are present in TLE and may contribute to neurocognitive problems. These studies demonstrate the underappreciated role of brainstem networks in epilepsy and may lead to novel neuromodulation targets to treat or prevent deleterious brain network effects of seizures in TLE.

Functional connectivity disturbances of the ascending reticular activating system in temporal lobe epilepsy.

OBJECTIVE: Seizures in temporal lobe epilepsy (TLE) disturb brain networks and lead to connectivity disturbances. We previously hypothesised that recurrent seizures in TLE may lead to abnormal connections involving subcortical activating structures including the ascending reticular activating system (ARAS), contributing to neocortical dysfunction and neurocognitive impairments. However, no studies of ARAS connectivity have been previously reported in patients with epilepsy. METHODS: We used resting-state functional MRI recordings in 27 patients with TLE (67% right sided) and 27 matched controls to examine functional connectivity (partial correlation) between eight brainstem ARAS structures and 105 cortical/subcortical regions. ARAS nuclei included: cuneiform/subcuneiform, dorsal raphe, locus coeruleus, median raphe, parabrachial complex, pontine oralis, pedunculopontine and ventral tegmental area. Connectivity patterns were related to disease and neuropsychological parameters. RESULTS: In control subjects, regions showing highest connectivity to ARAS structures included limbic structures, thalamus and certain neocortical areas, which is consistent with prior studies of ARAS projections. Overall, ARAS connectivity was significantly lower in patients with TLE than controls (p<0.05, paired t-test), particularly to neocortical regions including insular, lateral frontal, posterior temporal and opercular cortex. Diminished ARAS connectivity to these regions was related to increased frequency of consciousness-impairing seizures (p<0.01, Pearson's correlation) and was associated with impairments in verbal IQ, attention, executive function, language and visuospatial memory on neuropsychological evaluation (p<0.05, Spearman's rho or Kendell's tau-b). CONCLUSIONS: Recurrent seizures in TLE are associated with disturbances in ARAS connectivity, which are part of the widespread network dysfunction that may be related to neurocognitive problems in this devastating disorder.