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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Performance discrepancies on the California Verbal Learning Test: Second Edition (CVLT-II) after traumatic brain injury.

One hundred fourteen patients with traumatic brain injury (TBI), selected from a 5-year series of consecutive rehabilitation referrals, completed the California Verbal Learning Test -- Second Edition (CVLT-II) within 1 year after injury. Various performance contrasts (i.e., proactive interference, retroactive interference, rapid forgetting, and retrieval problems) were evaluated. Initial analyses revealed higher rates of rapid forgetting in the TBI group as compared to the standardization sample. Follow-up analyses between those patients with and without unusual degrees of rapid forgetting did not reveal any significant differences between these groups on demographic or neurological variables (p>0.10 for all variables). It is concluded that performance discrepancies on the CVLT-II should never be used in isolation to determine the presence or absence of acquired cerebral or memory impairment. However, regardless of the cause, such discrepancies may still be relevant for clinical treatment recommendations.

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.

Criterion validity of the California Verbal Learning Test-Second Edition (CVLT-II) after traumatic brain injury.

The California Verbal Learning Test-Second Edition (CVLT-II) was performed by 200 participants, divided into moderate-severe traumatic brain injury (n=43), mild traumatic brain injury (n=57) and demographically matched control (n=100) groups. Participants with complicating premorbid histories or who scored below 15/16 on the CVLT-II forced choice recognition trial were excluded. There were statistically significant (p<.0001) effects of group status on the CVLT-II total recall discriminability and recognition discriminability indices. Logistic regression revealed that, in the classification of control versus moderate-severe traumatic brain injury, CVLT-II variables were accurate 66-71% overall, but false positive rates ranged from 49 to 54%. In conclusion, average scores on the CVLT-II differ meaningfully between patients with various degrees of severity of traumatic brain injury and controls, but this test should not be used in isolation to determine the presence or absence of acquired memory impairment.