Differentiating Epileptic and Psychogenic Non-Epileptic Seizures Using Machine Learning Analysis of EEG Plot Images.

The treatment of epilepsy, the second most common chronic neurological disorder, is often complicated by the failure of patients to respond to medication. Treatment failure with anti-seizure medications is often due to the presence of non-epileptic seizures. Distinguishing non-epileptic from epileptic seizures requires an expensive and time-consuming analysis of electroencephalograms (EEGs) recorded in an epilepsy monitoring unit. Machine learning algorithms have been used to detect seizures from EEG, typically using EEG waveform analysis. We employed an alternative approach, using a convolutional neural network (CNN) with transfer learning using MobileNetV2 to emulate the real-world visual analysis of EEG images by epileptologists. A total of 5359 EEG waveform plot images from 107 adult subjects across two epilepsy monitoring units in separate medical facilities were divided into epileptic and non-epileptic groups for training and cross-validation of the CNN. The model achieved an accuracy of 86.9% (Area Under the Curve, AUC 0.92) at the site where training data were extracted and an accuracy of 87.3% (AUC 0.94) at the other site whose data were only used for validation. This investigation demonstrates the high accuracy achievable with CNN analysis of EEG plot images and the robustness of this approach across EEG visualization software, laying the groundwork for further subclassification of seizures using similar approaches in a clinical setting.

The Gartland classification for expediting supracondylar humerus fracture triage: a collaborative approach to structured reporting between pediatric radiologists and orthopedists.

BACKGROUND: The modified Gartland classification is an important tool for evaluation of pediatric supracondylar humerus fractures (SCHF) because it can direct treatment decisions. Gartland type I can be managed outpatient, while emergent surgical consult occurs with type II and III. This study assesses the interobserver reliability of the Gartland classification between pediatric radiologists and orthopedic providers. METHODS: A retrospective review of 320 children diagnosed with a SCHF at a single tertiary children's hospital during 2022 was conducted. The Gartland classification documented in the radiographic report by a pediatric radiologist and the classification documented in the first encounter with an orthopedic provider was collected. Kappa value was used to assess interobserver reliability of classifications between radiologists and orthopedic providers. A second group of 76 Gartland type I SCHF from 2015, prior to our institution's implementation of structured reporting, was reviewed for comparison of unnecessary orthopedic consults at initial presentation. RESULTS: The Gartland classification has excellent interobserver reliability between radiologists and orthopedic providers with 90 % (289/320) agreement and kappa of 0.854 (confidence interval: 0.805-0.903). The most frequent disagreement that occurred was fractures classified as type II by radiology and type III by orthopedics. There were similar rates of consults for the 2015 and 2022 cohorts (p = 0.26). CONCLUSION: The Gartland classification system is a reliable and effective tool for communication between radiologists and orthopedic providers. Implementing a structured reporting system has the potential to improve triage efficiency for SCHF.

Speech and Swallowing Outcomes of Surgically Managed Cervical Chordoma: A Case Series.

OBJECTIVES: Cervical chordoma is a rare, low-grade primary bone tumor occurring in the axial skeleton. Due to challenges in surgical exposure caused by anatomic location, patients may experience dysfunction in speech and swallowing. The objective of this study was to characterize speech and swallowing outcomes for patients undergoing surgical resection of cervical chordoma. Moreover, we detail in-depth two cases with similar initial presentations to compare prognostic factors and management strategies. METHODS: Eleven patients with histologically confirmed cervical chordoma treated between 1993 and 2020 were included in this retrospective case series. Outcomes measured included overall survival, disease-free survival, need for enteral feeds, as well as results of modified barium swallow study (MBSS) and fiberoptic laryngoscopy. RESULTS: The mean age at diagnosis was 55.9 years. The patient population was 81.8% male. Mean survival after diagnosis was 96 months. Four (36.4%) patients required post-operative MBSS and demonstrated aspiration. All four of these patients presented with tumors in the superior cervical spine and received surgeries utilizing anterior approaches. Of the four, 2 required enteral feeds long-term. Four (36.4%) patients endorsed dysphonia. One patient developed post-operative right vocal fold paresis. The remaining three patients experienced stable dysphonia pre- and post-operatively. Additionally, three (27%) patients required tracheostomy placement, two of which remained in place long-term. CONCLUSIONS: Dysphagia is a common side effect of cervical chordoma resection. It is associated with the use of an anterior approach during resection and with tumors located in the superior cervical spine. Patients with postoperative dysphagia should receive early multidisciplinary swallow rehabilitation. LEVEL OF EVIDENCE: 4 Laryngoscope, 2024.

Anticancer effects of thymoquinone in head and neck squamous cell carcinoma: A scoping review.

Objective: Thymoquinone (TQ), the active constituent of Nigella sativa, has been shown to have anticancer effects in head and neck squamous cell carcinoma (HNSCC). This review aims to outline the properties of TQ, the known drivers in HNSCC formation, and summarize the anticancer effects of TQ in SCC. Data Sources: Three databases (PubMed, Embase, and Google Scholar) were queried for the key words "thymoquinone squamous cell carcinoma." Review Methods: Publications that were not original research and publications that did not have full-text available for review were excluded. Results: Sixteen research articles met the inclusion criteria. Our review demonstrates that TQ-induced cytotoxicity is associated with increased expression and activity of the tumor suppressor p53, proapoptotic proteins Bax and caspases, as well as decreased expression and activity of antiapoptotic proteins Bcl-2 and Mdm2. Additionally, TQ modulates cell-survival pathways such as the PI3k/Akt pathway. TQ synergizes with therapeutics including cisplatin and radiation. Early TQ administration may prevent carcinogenesis via upregulation of antioxidant enzymes, and TQ administration in the presence of cancer can result in disease mitigation via induction of oxidative stress. Conclusion: TQ acts as an upregulator of proapoptotic pathways and downregulator of antiapoptotic pathways, modulates the oxidative stress balance in tumor development, and works synergistically alongside other chemotherapeutics to increase cytotoxicity. TQ has the potential to prevent carcinogenesis in patients who are at high-risk for SCC and adjuvant treatment for SCC patients undergoing conventional treatments. Future studies should aim to identify specific populations in which TQ's effects would be the most beneficial. Level of Evidence: Not available.

Current status of sinonasal cancer survivorship care.

Sinonasal cancer is a heterogeneous orphan disease of diverse histologies, each with distinct clinical, oncologic, and toxicity profiles. Because of the comparative rarity of these cancers, sinonasal cancers are treated as a grouped diagnosis despite their clinical and biological heterogeneity. Multimodality treatment with a combination of surgery, chemotherapy, and/or radiotherapy is the standard-of-care for advanced-stage patients but there are few surveillance or follow-up practice guidelines or formalized survivorship care pathways. A scoping literature review was conducted via PubMed, EMBASE, and Google Scholar. A total of 112 studies were included, which were grouped along the following topics: surveillance, second primary tumors, quality of life, and symptom burden. Sinonasal cancer tends to exhibit a higher rate of local failure and occur in a delayed fashion compared to mucosal malignancies of the head and neck. Moreover, the site of failure and time-varying risk of recurrence is histology-specific. Following multimodality treatment of the skull base, patients may experience endocrine, visual, auditory, sinonasal, olfactory, and neurocognitive deficits, as well as psychosocial impairments that impact multiple physical and neuropsychological domains, resulting in diminished quality of life. Sinonasal cancer patients would benefit from tailored, histology-specific survivorship programs to address the recurrence, second primary, and functional impairments resulting from disease and treatment toxicity.

Does American Society of Anesthesiologist classification effect hospital course and postoperative complications following oral and maxillofacial surgical procedures?

OBJECTIVE: The purpose of the present study was to assess the duration of operative time and outcomes related to patients with an increased American Society of Anesthesiologists (ASA) Physical Status classification in the setting of hospital-based maxillofacial surgical procedures. STUDY DESIGN: The study was a retrospective multi-institutional cohort study using the American College of Surgeons National Surgical Quality Improvement Program database to enroll patients who underwent maxillofacial procedures between 2012 and 2019. The primary independent variable was ASA Physical Status Classification (I, II, III, IV). Descriptive, univariate, and multiple logistic regression statistics were used to evaluate the relationship between ASA classification, body mass index (BMI), operative time, and perioperative complications. RESULTS: The study cohort was comprised of 1807 patients, with 946 males and 861 females. The ASA Physical Status Classification ranged from class I to IV. On bivariate analysis, patients classified as ASA III (286 [IQR 152-503], P < .001) and ASA IV (412 [IQR 156.5-547.5], P = .003) were associated with longer operative times. The risk of perioperative complications was 2.6% for ASA I patients (n = 19), 6.3% for ASA II (n = 48; P = .005), 24.5% for ASA III (n = 76; P < .001), and 55.0% for ASA IV (n = 11; P < .001). On multivariate-adjusted analysis, using ASA I as the reference, ASA III (ß +53.2 minutes, 95% CI +28.6 to +77.8, P < .001) and ASA IV (ß +81.5 minutes, 95% CI +21.0 to +141.9, P = .008) were variables associated with longer operative time. CONCLUSIONS: Increased ASA Physical Status Classification was associated with increased operative time and perioperative complications.

Is lobectomy sufficient for multifocal papillary thyroid microcarcinoma?

IMPORTANCE: Multifocal papillary thyroid microcarcinoma (PTMC) has been associated with a higher incidence of lymph node involvement, bilateral involvement, and extrathyroidal extension compared to unifocal papillary thyroid cancer (PTC). OBJECTIVE: To describe the incidence and determinants of survival for patients with multifocal PTMC using the Surveillance, Epidemiology, and End Result (SEER) database. DESIGN, SETTING, PARTICIPANTS: The SEER registry was utilized to calculate survival trends for patients with PTMC between 2010 and 2015. Patient data was then analyzed with respect to age, sex, race, multifocality, and types of surgery rendered. MAIN OUTCOMES AND MEASURES: Overall Survival (OS) and Disease Specific Survival (DSS). RESULTS: 22,283 cases of papillary thyroid microcarcinoma (T1a N0 M0) were identified. The cohort was composed of 82.6 % females, and about 82 % of patients were of white race. The mean age at diagnosis was 51.9 years. Multifocal PTMC was present in 32.2 % of the tumors (n = 7186). 73.9 % of patients underwent total thyroidectomy and 23.0 % received lobectomy. OS at 2 and 5 years was 98 % and 95 %, respectively. Multivariate analysis revealed that age, sex, and multifocality were determinants of OS. Only age was a determinant of DSS. Kaplan-Meier survival analysis revealed that multifocal PTMC had similar mean OS between lobectomy and total thyroidectomy patients (69.59 months versus 69.82 months). CONCLUSIONS AND RELEVANCE: PTMC has a good prognosis. Our analysis revealed that age was a determinant of OS and DSS; sex and multifocality were also prognosticators for OS. The type of surgery, whether lobectomy or total thyroidectomy, was not a determinant of survival in multifocal PTMC.

Anaplastic Transformation of Differentiated Thyroid Carcinoma.

OBJECTIVES: Anaplastic thyroid carcinoma (ATC) is a rare but highly aggressive form of thyroid cancer. Increasingly, patients with ATC present with concurrent foci of well-differentiated thyroid carcinoma (WDTC); however, the significance of these pathologic findings remains unclear. The objective of this study is to determine whether the presence of WDTC within anaplastic tumors is a prognosticator of survival. METHODS: A retrospective cohort study of all cases of biopsy-proven ATC managed at a tertiary care academic medical center from 2002 to 2020 was performed. Mean age at diagnosis, median survival time, and locations of distant metastases were assessed. The impact of clinical markers such as presence of differentiation, demographic variables, and oncologic information on overall survival was also determined via univariate and multivariate analysis. RESULTS: Forty-five patients were included in this study. The mean age at diagnosis was 69.1 years. Median survival time was 6.1 months after diagnosis. The most common location of distant metastases was the lung (40%). The presence of limited areas of WDTC in patients with predominantly anaplastic thyroid tumors was not significantly associated with improved outcomes (p = 0.509). Smaller tumor size and use of chemotherapy in ATC patients were significantly associated with prolonged survival (p = 0.026 and 0.010, respectively). CONCLUSIONS: Clinical outcomes for ATC remain poor. The presence of foci of differentiation within anaplastic thyroid tumors does not appear to improve overall survival-the anaplastic component evidently drives outcomes. Further studies into novel therapies are needed to improve survival in ATC. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:437-442, 2023.

Stage-Specific Survival in Young Patients With Oral Tongue Squamous Cell Carcinoma.

OBJECTIVE: To determine demographic factors and clinicopathologic characteristics associated with survival in young patients (age <45 years) with early- (I-II) or late-stage (III-IV) oral tongue squamous cell carcinoma (OTSCC). STUDY DESIGN: Retrospective database review. SETTING: National Cancer Database. METHODS: A retrospective review of 3262 OTSCC cases in young patients between 2005 and 2014 was performed by using data from the National Cancer Database. Factors affecting 2-year survival in patients with early- and late-stage disease were evaluated via univariate and multivariate analyses. RESULTS: Overall, 1899 patients with early-stage OTSCC and 1363 with late-stage OTSCC were analyzed. In multivariate analysis of early-stage OTSCC, high tumor grade (hazard ratio, 2.08 [95% CI, 1.45-2.99]), local metastasis (2.85 [1.37-5.95]), and tumor size (1.04 [1.02-1.07]) were predictors of mortality. In late-stage OTSCC, African American race (2.79 [1.40-5.56]), positive surgical margins (1.77 [1.07-2.93]), local metastasis (2.20 [1.03-4.72]), distant metastasis (11.66 [2.10-64.73]), depth of invasion (1.03 [1.01-1.05]), and tumor size (1.01 [1.003-1.01]) were predictors of mortality. Subset analysis of clinical N0-stage tumors revealed that treatment with surgery alone was associated with improved survival (P < .001). CONCLUSION: Positive lymph nodes, high tumor grade, and larger tumor size were associated with increased mortality risk in early- and late-stage young OTSCC. More aggressive up-front treatment, including extirpative surgery and elective neck dissection, may be associated with improved outcomes and should be considered in early-stage cases with high-risk features.

A Rare Case of Laryngeal Non-IgM Lymphoplasmacytic Lymphoma.

Laryngeal lymphoplasmacytic lymphoma has been previously reported only a handful of times in the literature. It can be difficult to diagnose without significant histologic workup and proper methodology. Here, we demonstrate the first known case of laryngeal lymphoplasmacytic lymphoma with non-immunoglobulin M (IgM) features. In this case report, a 79-year-old female with seropositive rheumatoid arthritis presented with five months of dysphonia and dyspnea on exertion. Lab studies revealed high levels of serum IgA and IgG. Flexible laryngoscopy and computed tomography of the neck showed a left supraglottic submucosal mass, which was surgically excised with a carbon dioxide laser. The histology of the mass confirmed the diagnosis of lymphoplasmacytic lymphoma. The patient was treated with 30.6 Gy of radiation therapy and eight cycles of rituximab with successful remission of her lymphoma and no evidence of disease recurrence six months after treatment completion. Lymphoplasmacytic lymphoma without corresponding IgM gammopathy is unusual and has been shown to have a higher frequency of extramedullary involvement. This is the first known manifestation of non-IgM lymphoplasmacytic lymphoma in the larynx.

Sinonasal Papillomas: 10-Year Retrospective Analysis of Etiology, Epidemiology, and Recurrence.

OBJECTIVES: To examine the epidemiology, subtypes, trends over time, and predictive factors for recurrence and malignant transformation of sinonasal papillomas. METHODS: A retrospective chart review of 118 patients with sinonasal papillomas from 2009 to 2019 was conducted at the University of California, Los Angeles. This study is a follow-up to a previously published study from 2000 to 2009 at the same academic center. RESULTS: The mean age was at presentation was 58.5 years, with a 2:1 male to female ratio, and average follow-up of 30.1 months. The rate of recurrence after complete resection was 19% with an average of 32.6 months to recurrence. The time to recurrence followed a bimodal distribution with 57% of cases recurring within 24 months (mean = 10) and 43% from 40 to 103 months (mean = 61). The proportion of the inverted papillomas rose from 38% in 2000-2004 to 89.6% in 2015-2019. Patients presenting at a younger age had a higher chance of recurrence (mean age 52 with recurrence vs. 61 without recurrence). Age did not correlate with histopathologic transformation in surgical pathology. Furthermore, histopathological transformation did not raise the chance of recurrence. Smoking, alcohol use, chronic rhinosinusitis, and allergic rhinitis were not associated with any of the outcome measures in this study. The most significant factor predicting recurrence, beside age at presentation, was the history of two or more prior sinus surgeries for papillomas or other reasons (OR = 3.52 and 5.81). CONCLUSION: This study explored the features of sinonasal papillomas as well as the risk factors for recurrence and transformation. Younger age at presentation and two or more prior surgeries for papillomas were associated with recurrence. Time to recurrence followed a bimodal distribution, with late recurrences happenning from 40 to 103 months after surgery, emphasizing the importance of long-term follow-up for timely resection of tumors and prevention of malignancy.

Label-free, real-time detection of perineural invasion and cancer margins in a murine model of head and neck cancer surgery.

Surgical management of head and neck cancer requires a careful balance between complete resection of malignancy and preservation of function. Surgeons must also determine whether to resect important cranial nerves that harbor perineural invasion (PNI), as sacrificing nerves can result in significant morbidity including facial paralysis. Our group has previously reported that Dynamic Optical Contrast Imaging (DOCI), a novel non-invasive imaging system, can determine margins between malignant and healthy tissues. Herein, we use an in vivo murine model to demonstrate that DOCI can accurately identify cancer margins and perineural invasion, concordant with companion histology. Eight C3H/HeJ male mice were injected subcutaneously into the bilateral flanks with SCCVIISF, a murine head and neck cancer cell line. DOCI imaging was performed prior to resection to determine margins. Both tumor and margins were sent for histologic sectioning. After validating that DOCI can delineate HNSCC margins, we investigated whether DOCI can identify PNI. In six C3H/HeJ male mice, the left sciatic nerve was injected with PBS and the right with SCCVIISF. After DOCI imaging, the sciatic nerves were harvested for histologic analysis. All DOCI images were acquired intraoperatively and in real-time (10 s per channel), with an operatively relevant wide field of view. DOCI values distinguishing cancer from adjacent healthy tissue types were statistically significant (P < 0.05). DOCI imaging was also able to detect perineural invasion with 100% accuracy compared to control (P < 0.05). DOCI allows for intraoperative, real-time visualization of malignant and healthy tissue margins and perineural invasion to help guide tumor resection.

Solitary Fibrous Tumors of the Head and Neck: A Single-Institution Study of 52 Patients.

Objective: To evaluate the clinicopathologic characteristics of head and neck solitary fibrous tumors and features that may predict tumor recurrence. Study Design: Retrospective review. Setting: University of California-Los Angeles Medical Center. Methods: A single-center retrospective study was conducted on pathologically confirmed cases of head and neck solitary fibrous tumors between 1996 and 2021. Patient demographics, clinical course, and histopathologic features were evaluated. Recurrence-free survival was estimated via Kaplan-Meier analysis. Results: A total of 52 patients were reviewed. The average patient age was 54.7 years (range, 15-89). The most common subsite was the orbit (53.8%, n = 28), but other involved areas included the nasopharynx, paranasal sinuses, and scalp. The median tumor size was 2.95 cm (range, 1.3-11.2). Strong STAT6 (100%) and CD34 (97.9%) expression was observed on immunohistochemistry. Almost all patients were initially managed with wide local excision; 82% of patients (n = 14) had positive margins on pathologic review; and 15% (n = 4) had recurrence at a median 28.5 months (range, 10-113). White patient race was the only significant predictor of tumor recurrence. Patient age (≥55 years), tumor size (≥4), high mitotic rate, and disease subsite were not associated with recurrence. Conclusion: Head and neck solitary fibrous tumors demonstrate a significantly larger local recurrence rate as compared with their rate of metastasis. They can recur many years following initial therapy, warranting long-term surveillance and follow-up to assess for tumor recurrence.

Secondary syphilis of the oropharynx and cervical lymph nodes: a case report.

Secondary syphilis rarely affects the head and neck including the oropharynx and cervical lymph nodes. These patients present with throat pain, cystic/necrotic lymphadenopathy, and mucosal swelling. Sometimes this constellation of symptoms can be mistaken for head and neck cancer. We report a case of an enlarging throat and painless cystic neck mass in a transgender woman in her forties who was initially suspected to have oropharyngeal squamous cell carcinoma. A subsequent workup revealed the presence of spirochetes without cellular atypia consistent with secondary syphilis. We include the ultrasonography images as well as an endoscopic photograph of the oropharyngeal manifestation in this report.

Intractable Hiccups Caused by Diaphragmatic Eventration.

Intractable hiccups are a rare yet debilitating pathology with a broad differential and often indicate a more serious underlying pathology, which can range from neoplasms to structural abnormalities. In this case report, we present a 64-year-old male with seven months of intractable hiccups determined to be caused by eventration of the right hemidiaphragm. The patient was treated with baclofen to treat the hiccups pharmacologically. He was also prescribed voice therapy to establish rescue breathing techniques and reduce laryngospasm. Finally, he was referred to thoracic surgery for further evaluation and potential surgical intervention should his diaphragmatic eventration worsen or cause hypoxemia. To our knowledge, this is the first reported case of an association between diaphragmatic eventration and intractable hiccups. It is important to highlight this addition to the broad differential of intractable hiccups and to emphasize an interdisciplinary approach to workup and treatment of intractable hiccups.

Predictors of Nodal Metastasis in Cutaneous Head and Neck Cancers.

PURPOSE OF REVIEW: The complex and varied drainage patterns in the head and neck present a challenge in the regional control of cutaneous neoplasms. Lymph node involvement significantly diminishes survival, often warranting more aggressive treatment. Here, we review the risk factors associated with lymphatic metastasis, in the context of the evolving role of sentinel lymph node biopsy. RECENT FINDINGS: In cutaneous head and neck melanomas, tumor thickness, age, size, mitosis, ulceration, and specific histology have been associated with lymph node metastasis (LNM). In head and neck cutaneous squamous cell carcinomas, tumor thickness, size, perineural invasion, and immunosuppression are all risk factors for nodal metastasis. The risk factors for lymph node involvement in Merkel cell carcinoma are not yet fully defined, but emerging evidence indicates that tumor thickness and size may be  associated with regional metastasis. The specific factors that predict a greater risk of LNM for cutaneous head and neck cancers generally include depth of invasion, tumor size, mitotic rate, ulceration, immunosuppression, and other histopathological factors.

Modular polymer platform as a novel approach to head and neck cancer therapy.

Head and neck cancer is the sixth most common cancer in the world, with more than 300,000 deaths attributed to the disease annually. Aggressive surgical resection often with adjuvant chemoradiation is the cornerstone of treatment. However, the necessary chemoradiation treatment can result in collateral damage to adjacent vital structures causing a profound impact on quality of life. Here, we present a novel polymer of poly(lactic-co-glycolic) acid and polyvinyl alcohol that can serve as a versatile multidrug delivery platform as well as for detection on cross-sectional imaging while functioning as a fiduciary marker for postoperative radiotherapy and radiotherapeutic dosing. In a mouse xenograft model, the dual-layered polymer composed of calcium carbonate/thymoquinone was used for both polymer localization and narrow-field infusion of a natural therapeutic compound. A similar approach can be applied in the treatment of head and neck cancer patients, where immunotherapy and traditional chemotherapy can be delivered simultaneously with independent release kinetics.

Ex vivo hypercellular parathyroid gland differentiation using dynamic optical contrast imaging (DOCI).

Primary hyperparathyroidism, often caused by a single adenoma (80-85%) or four-gland hyperplasia (10-15%), can lead to elevated parathyroid hormone (PTH) levels and resultant hypercalcemia. Surgical excision of offending lesions is the standard of care, as the removal of pathologic adenomas reduces PTH and calcium values to baseline. The small size, variable location, and indistinct external features of parathyroid glands can make their identification quite challenging intraoperatively. Our group has developed the dynamic optical contrast imaging (DOCI) technique, a novel realization of dynamic temporally dependent measurements of tissue autofluorescence. In this study, we evaluated the efficacy of using the DOCI technique and normalized steady-state fluorescence intensity data for differentiating types of human parathyroid and thyroid tissues. We demonstrate that the DOCI technique has the capability to distinguish normal parathyroid tissue from diseased parathyroid glands as well as from adjacent healthy thyroid and adipose tissue across 8 different spectral channels between 405nm-600nm (p<0.05). Patient tissue DOCI data was further analyzed with a logistic regression classifier trained across the 8 spectral channels. After computer training, the computer-aided identification was able to accurately locate hypercellular parathyroid tissue with 100% sensitivity and 98.8% specificity within the captured DOCI image.

Brain Stimulation Using Responsive Neurostimulation Improves Verbal Memory: A Crossover Case-Control Study.

BACKGROUND: The effects of brain stimulation on memory formation in humans have shown conflicting results in previous studies. We hypothesized that direct cortical stimulation using an implanted responsive neurostimulation (RNS) system will improve memory. OBJECTIVE: To evaluate whether direct cortical stimulation using RNS improves memory as measured with recall scores of a list-learning task. METHODS: During outpatient visits, a list-learning task (Hopkins Verbal Learning Test-Revised) was administered to 17 patients with RNS implants. Patients were read a list of 12 semantically related words and asked to recall the list after 3 different learning trials. True or sham stimulations were performed for every third word presented for immediate recall. Most patients had frontotemporal network stimulation-one patient each had insular and parietal stimulations. After a 20-min delay, they were asked to recall the list again, first freely and then through a "yes/no" recognition paradigm. A crossover design was used in which half the patients had true stimulation during the initial visit and half had sham stimulation-followed by crossover to the other group at the next visit. RESULTS: The Hopkins Verbal Learning Test-Revised delayed recall raw score was higher for the stimulation condition compared with the nonstimulation condition (paired t -test, P = .04, effect size d = 0.627). CONCLUSION: Verbal memory improves by direct cortical stimulation during a list-learning task. The RNS system can be effectively used in memory research using direct cortical stimulation. This study has implications in the development of neurostimulation devices for cognitive enhancement in conditions such as epilepsy, dementia, and traumatic brain injury.