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Efficacy of deep brain stimulation for the treatment of anorexia nervosa: a systematic review and network meta-analysis of patient-level data

Annabelle Shaffer, Anant Naik, Maria Bederson, Paul M. Arnold, and Wael Hassaneen

OBJECTIVE

Deep brain stimulation (DBS) has been approved as a therapy for movement disorders and obsessive-compulsive disorder. Recently, DBS has been studied in patients with anorexia nervosa (AN), which is a debilitating and life-threatening psychiatric disorder. Several stimulation locations have been tested without a clear indication of the best region. In this systematic review and network meta-analysis, the authors used patient-level data to identify stimulation targets with the greatest evidence for efficacy in increasing body mass index (BMI).

METHODS

A systematic search was performed on or before August 4, 2022, using PubMed/MEDLINE, Ovid, and Scopus. Articles were included if patient-level data were presented, patients were diagnosed with AN and treated with DBS, and 6 months or more of postoperative follow-up data were reported. Quality and risk of bias were assessed with the NIH assessment tools. Patient data were collected and stratified by stimulation location. A network meta-analysis was performed. This review was written in accordance with PRISMA guidelines for systematic reviews.

RESULTS

Eleven studies consisting of 36 patients were included. The mean age and BMI at the time of surgery were 38.07 (SD 11.64) years and 12.58 (SD 1.4) kg/m2, respectively. After 6 months of DBS, a significant difference in percentage change in BMI was found between the nucleus accumbens and subcallosal cingulate cortex (SCC) (SMD 0.78; 95% CI 0.10, 1.45) and between the SCC and ventral anterior limb of the internal capsule (SMD −1.51; 95% CI −2.39, −0.62). Similarly, at 9–12 months, a significant difference in percentage change in BMI was found between the SCC and ventral anterior limb of the internal capsule (SMD −1.18; 95% CI −2.21, −0.15). With hierarchical ranking, this study identified SCC as the most supported stimulation location for BMI change at 6 and 9–12 months (P-scores 0.9449 and 0.9771, respectively).

CONCLUSIONS

Several DBS targets have been tested for AN, and this study identified the SCC as the most supported region for BMI change. However, further studies with blinded on/off periods are necessary to confirm this finding.

In Neurosurgical Focus Volume 54 (2023): Issue 2 (Feb 2023): Neurosurgical Management of Psychiatric Disease

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Intracranial subsecond dopamine measurements during a “sure bet or gamble” decision-making task in patients with alcohol use disorder suggest diminished dopaminergic signals about relief

Brittany Liebenow, Angela Jiang, Emily DiMarco, Thomas Wilson, Mustafa S. Siddiqui, Ihtsham ul Haq, Adrian W. Laxton, Stephen B. Tatter, and Kenneth T. Kishida

OBJECTIVE

To the authors’ knowledge, no data have been reported on dopamine fluctuations on subsecond timescales in humans with alcohol use disorder (AUD). In this study, dopamine release was monitored in 2 patients with and 2 without a history of AUD during a “sure bet or gamble” (SBORG) decision-making task to begin to characterize how subsecond dopamine responses to counterfactual information, related to psychological notions of regret and relief, in AUD may be altered.

METHODS

Measurements of extracellular dopamine levels were made once every 100 msec using human voltammetric methods. Measurements were made in the caudate during deep brain stimulation electrode implantation surgeries (for treatment of movement disorders) in patients who did (AUD, n = 2) or did not (non-AUD, n = 2) have a history of AUD. Participants performed an SBORG decision-making task in which they made choices between sure bets and 50%-chance monetary gamble outcomes.

RESULTS

Fast changes were found in dopamine levels that appear to be modulated by “what could have been” and by patients’ AUD status. Positive counterfactual prediction errors (related to relief) differentiated patients with versus without a history of AUD.

CONCLUSIONS

Dopaminergic encoding of counterfactual information appears to differ between patients with and without AUD. The current study has a major limitation of a limited sample size, but these data provide a rare insight into dopaminergic physiology during real-time decision-making in humans with an addiction disorder. The authors hope future work will expand the sample size and determine the generalizability of the current results.

In Neurosurgical Focus Volume 54 (2023): Issue 2 (Feb 2023): Neurosurgical Management of Psychiatric Disease

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Introduction. Neurosurgical neuroscience

Sameer A. Sheth, G. Rees Cosgrove, and Nicole C. R. McLaughlin

In Neurosurgical Focus Volume 54 (2023): Issue 2 (Feb 2023): Neurosurgical Management of Psychiatric Disease

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Letter to the Editor. The life and death of Thierry de Martel

Romain Carron

In Neurosurgical Focus Volume 54 (2023): Issue 2 (Feb 2023): Neurosurgical Management of Psychiatric Disease

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Neurosurgery for psychiatric disorders: reviewing the past and charting the future

Luke Bauerle, Charles Palmer, Claudia A. Salazar, Thomas Larrew, Suzanne E. Kerns, E. Baron Short, Mark S. George, and Nathan C. Rowland

Surgical techniques targeting behavioral disorders date back thousands of years. In this review, the authors discuss the history of neurosurgery for psychiatric disorders, starting with trephination in the Stone Age, progressing through the fraught practice of prefrontal lobotomy, and ending with modern neurosurgical techniques for treating psychiatric conditions, including ablative procedures, conventional deep brain stimulation, and closed-loop neurostimulation. Despite a tumultuous past, psychiatric neurosurgery is on the cusp of becoming a transformative therapy for patients with psychiatric dysfunction, with an ever-increasing evidence base suggesting reproducible and ethical therapeutic benefit.

In Neurosurgical Focus Volume 54 (2023): Issue 2 (Feb 2023): Neurosurgical Management of Psychiatric Disease

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Novel psychiatric disorders following mild traumatic brain injury: a retrospective multivariable analysis with screening recommendations

Alexander M. Ballatori, Ariana Zargarian, Alison Haddad, and Shane Shahrestani

OBJECTIVE

Concussions are a form of mild traumatic brain injury (mTBI) that most commonly occur after blunt trauma to the head and may result in temporary loss of consciousness. These patients are typically comanaged by neurocritical care specialists, neurologists, and neurosurgeons depending on the severity of disease. The purpose of this study was twofold: 1) evaluate how patient demographic characteristics impact the development of novel psychiatric disorders (NPDs) after mTBI; and 2) develop screening recommendations to identify patients with NPDs.

METHODS

The authors used data from the 2010–2019 National Readmissions Database of the Healthcare Cost and Utilization Project. Patients who were readmitted for mTBI within a year of their first admission between 2010 and 2019 were identified (n = 206,070). The association between patient demographic characteristics and the emergence of NPDs after mTBI was examined using multivariable binomial regression analysis. Density plots were used to examine diagnostic patterns for NPDs.

RESULTS

The mean ± SD age of all patients was 50.9 ± 26.2 years, and 43.9% of patients were female. Overall, an additional 818 (0.40%) patients were reported to have novel suicidal ideation (SI), 3866 (1.9%) novel depression, 3449 (1.7%) novel anxiety, and 88 (0.043%) novel homicidal ideation (HI) after mTBI. Younger age (OR 0.9775, 95% CI 0.9705–0.9848, p < 0.0001) and reduced Charlson Comorbidity Index (CCI) score (OR 0.9155, 95% CI 0.8539–0.9774, p = 0.010) may predict novel SI, and female sex (OR 0.7464, 95% CI 0.6026–0.9214, p = 0.0069) may be inversely related to novel SI after mTBI. Also, multivariable analysis found that female sex (OR 1.1774, 95% CI 1.0654–1.3016, p = 0.0014) and Medicare/Medicaid insurance type (OR 0.9381, 95% CI 0.8983–0.9797, p = 0.0039) may predict novel anxiety after mTBI. Similarly, younger age (OR 0.9956, 95% CI 0.9923–0.9989, p = 0.0096), higher CCI score (OR 1.0363, 95% CI 1.0099–1.0629, p = 0.0062), and Medicare/Medicaid insurance type (OR 0.9386, 95% CI 0.8998–0.9789, p = 0.0032) may predict novel depression. Lastly, female sex (OR 0.3271, 95% CI 0.1467–0.6567, p = 0.0031) and increased median income (OR 0.8829, 95% CI 0.7930–0.9944, p = 0.049) were inversely proportional to novel HI after mTBI. The median time to diagnosis of NPD was 69.5 days for depression, 66.5 days for anxiety, 70.0 days for SI, and 66.5 days for HI.

CONCLUSIONS

Numerous patient demographic factors are significant predictors of the development of NPDs after mTBI and concussion. Screening for NPDs within 3 weeks and 3 months after mTBI may identify most patients at risk for developing novel postconcussive psychiatric conditions, including anxiety, depression, HI, and SI. Further studies are warranted to understand how patient demographic characteristics should dictate medical management and screening after mTBI and concussion.

In Neurosurgical Focus Volume 54 (2023): Issue 2 (Feb 2023): Neurosurgical Management of Psychiatric Disease

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Schizophrenia and neurosurgery: systematic review and theories

Rajeev R. Dutta, Bryce Picton, Nolan J. Brown, Chenyi Yang, Maxwell Lee, Hana Sung, Alexander M. Lopez, and Michelle Paff

OBJECTIVE

Despite its relatively low prevalence, schizophrenia has a high burden of illness due to its lifelong effects and the fact that it is often refractory to psychotropic treatment. This review investigated how neurosurgical interventions, primarily neuromodulation through deep brain stimulation (DBS), can mitigate treatment-refractory schizophrenia. Pathophysiological data and ongoing clinical trials were reviewed to suggest which targets hold promise for neurosurgical efficacy.

METHODS

A systematic review of the literature was conducted via an electronic search of the PubMed, Scopus, and Web of Science databases. Included papers were human or animal studies of neurosurgical interventions for schizophrenia conducted between 2012 and 2022. An electronic search of ClinicalTrials.gov and the International Clinical Trials Registry Platform was conducted to find ongoing clinical trials. The ROBINS-I (Risk of Bias in Nonrandomized Studies of Interventions) assessment tool was used to evaluate risk of bias in the study.

RESULTS

Eight human and 2 rat studies were included in the review. Of the human studies, 5 used DBS targeting the nucleus accumbens, subgenual anterior cingulate cortex, habenula, and substantial nigra pars reticulata. The remaining 3 human studies reported the results of subcaudate tractotomies and anterior capsulotomies. The rat studies investigated DBS of the nucleus accumbens and medial prefrontal cortex. Overall, human studies demonstrated long-term reduction in Positive and Negative Syndrome Scale scores in many participants, with a low incidence of surgical and psychological side effects. The rat studies demonstrated improved prepulse and latent inhibition in the targeted areas after DBS.

CONCLUSIONS

As identified in this review, recent studies have investigated the potential effects of therapeutic DBS for schizophrenia, with varying results. DBS targets that have been explored include the hippocampus, subgenual anterior cingulate cortex, habenula, substantia nigra pars reticulata, and medial prefrontal cortex. In addition to DBS, other neuromodulatory techniques such as neuroablation have been studied. Current evidence suggests that neuroablation in the subcaudate tract and anterior capsulotomy may be beneficial for some patients. The authors recommend further exploration of neuromodulation for treatment-refractory schizophrenia, under the condition that rigorous standards be upheld when considering surgical candidacy for these treatments, given that their safety and efficacy remain to be determined.

In Neurosurgical Focus Volume 54 (2023): Issue 2 (Feb 2023): Neurosurgical Management of Psychiatric Disease

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Stereotactic electroencephalography in epilepsy patients for mapping of neural circuits related to emotional and psychiatric behaviors: a systematic review

Christian G. Lopez Ramos, Hao Tan, Erin A. Yamamoto, Daniel R. Cleary, David J. Mazur-Hart, Maryam N. Shahin, and Ahmed M. Raslan

OBJECTIVE

Stereotactic electroencephalography (sEEG) is an increasingly utilized method for identifying electrophysiological processes underlying sensorimotor, cognitive, and emotional behaviors. In this review, the authors outline current research using sEEG to investigate the neural activity underlying emotional and psychiatric behaviors. Understanding the current structure of intracranial research using sEEG will inform future studies of psychiatric disease and therapeutics for effective neuromodulation.

METHODS

The authors conducted a comprehensive systematic review of studies according to PRISMA guidelines to investigate behaviors related to psychiatric conditions in patients with epilepsy undergoing monitoring with sEEG. Articles indexed on PubMed between 2010 and 2022 were included if they studied emotions or affective behaviors or met the National Institute of Mental Health Research Domain Criteria positive and negative valence domains. Data extracted from articles included study sample size, paradigms and behavioral tasks employed, cortical and subcortical targets, EEG analysis methods, and identified electrophysiological activity underlying the studied behavior. The Newcastle-Ottawa Scale was used to assess bias risk.

RESULTS

Thirty-two primary articles met inclusion criteria. Study populations ranged from 3 to 39 patients. The most common structures investigated were the amygdala, insula, orbitofrontal cortex (OFC), hippocampus, and anterior cingulate cortex (ACC). Paradigms, stimuli, and behavioral tasks widely varied. Time-frequency analyses were the most common, followed by connectivity analyses. Multiple oscillations encoded a variety of behaviors related to emotional and psychiatric conditions. High gamma activity was observed in the amygdala and anterior insula in response to aversive audiovisual stimuli and in the OFC in response to reward processing. ACC beta band power increases and hippocampal-amygdala beta coherence variations were predictive of worsening mood states. Insular and amygdalar theta oscillations encoded social pain and fear learning, respectively. Most studies performed passing recordings, allowing for the decoding of affective states and depression symptoms, while other studies utilized direct stimulation, such as in the OFC to improve mood symptoms.

CONCLUSIONS

Stereotactic EEG in epilepsy has identified multiple corticolimbic structures with specific oscillatory and synchronization activity underlying a diverse range of behaviors related to emotions and affective conditions. Given the heterogeneity of psychiatric conditions, sEEG provides an opportunity to study these neural correlates to develop personalized effective neuromodulatory treatments. Future studies should focus on optimizing paradigms and tasks to investigate a broad range of behavioral phenotypes that overlap across psychiatric conditions.

In Neurosurgical Focus Volume 54 (2023): Issue 2 (Feb 2023): Neurosurgical Management of Psychiatric Disease

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The Surgeon, or The Extraction of the Stone of Madness, by Jan Sanders van Hemessen (c 1500–1566)

Eric J. Chalif

The Surgeon, or The Extraction of the Stone of Madness is one of the most striking representations of neurosurgery in art. The focus of the painting is occupied by a surgeon who, with a concentrated gaze and wry smile, attempts to remove a stone from the forehead of an anguished young man who is tied to a chair, crying in agony. The artist of this dramatic work is the relatively obscure Jan Sanders van Hemessen (c 1500–1566). Hemessen lived in a time of artistic ferment in the Netherlands as conservative local traditions gave way to new ideas imported from Italy, which marked the beginning of the Romanism period. Romanists were aspiring young Netherlandish artists who traveled to Rome, Florence, Milan, and Venice to study the works of High Renaissance masters such as Michelangelo, Raphael, and Leonardo da Vinci. With these lessons in mind, they combined the typical features of early Netherlandish painting—a high degree of realism, the use of symbolic iconography, and a focus on genre painting and still life—with the dramatic gestures, heroic postures, chiaroscuro, space and volume, and grand humanistic themes of the Italian Renaissance. Hemessen’s interpretation of the allegory of the stone of madness reveals these Italian influences while also retaining the early Netherlandish tradition of realism and iconography, in which the objective world represents a realm of symbolic implication carrying allegorical moralistic messages. The predominant interpretation of The Surgeon, or The Extraction of the Stone of Madness is as a metaphor for stupidity and gullibility, a common theme in Netherlandish art of this time. As such, Hemessen’s painting symbolizes the limits of the medical profession and underscores the persistent hope for neurosurgery to treat psychiatric disease in the future.

In Neurosurgical Focus Volume 54 (2023): Issue 2 (Feb 2023): Neurosurgical Management of Psychiatric Disease

Open access

Cerebral tumor embolism from thyroid cancer treated by mechanical thrombectomy: illustrative case

Yuta Fujiwara, Kentaro Hayashi, Yohei Shibata, Tatsuya Furuta, Tomohiro Yamasaki, Kazuhiro Yamamoto, Masahiro Uchimura, Fumio Nakagawa, Mizuki Kambara, Hidemasa Nagai, and Yasuhiko Akiyama

BACKGROUND

Development in mechanical thrombectomy is progressing dramatically. Tumor embolism has been rarely reported on the basis of pathological study of the retrieved thrombus. Herein, the authors report a case of cerebral tumor embolism from advanced thyroid cancer, which was successfully treated with mechanical thrombectomy.

OBSERVATIONS

A 57-year-old man was diagnosed with thyroid cancer with multiple lung metastases and chemotherapy was planned. He experienced left hemiparesis and was bought to the emergency section of the authors’ hospital. Magnetic resonance angiography revealed right internal carotid artery occlusion and endovascular treatment was performed. Using a combination of aspiration catheter and stent retriever, white jelly-like embolus was retrieved. The pathological study demonstrated thyroid cancer embolism. Pulmonary vein invasion following lung metastasis of thyroid cancer was most presumably the cause of the tumor embolism.

LESSONS

Lung metastasis invading the pulmonary vein may be a cause of tumor embolism. Mechanical thrombectomy using a combination of stent retriever and aspiration catheter is effective in removing the tumor embolus and the pathological examination of the embolus is essential.

In Journal of Neurosurgery: Case Lessons Volume 5 (2023): Issue 5 (Jan 2023)