Differential Cognitive Effects of Unilateral Subthalamic Nucleus Deep Brain Stimulation for Parkinson's Disease.

OBJECTIVE: The aim of this study was to investigate the cognitive effects of unilateral directional versus ring subthalamic nucleus deep brain stimulation (STN DBS) in patients with advanced Parkinson's disease. METHODS: We examined 31 participants who underwent unilateral STN DBS (left n = 17; right n = 14) as part of an National Institutes of Health (NIH)-sponsored randomized, double-blind, crossover study contrasting directional versus ring stimulation. All participants received unilateral DBS implants in the hemisphere more severely affected by motor parkinsonism. Measures of cognition included verbal fluency, auditory-verbal memory, and response inhibition. We used mixed linear models to contrast the effects of directional versus ring stimulation and implant hemisphere on longitudinal cognitive function. RESULTS: Crossover analyses showed no evidence for group-level changes in cognitive performance related to directional versus ring stimulation. Implant hemisphere, however, impacted cognition in several ways. Left STN participants had lower baseline verbal fluency than patients with right implants (t [20.66 = -2.50, p = 0.02]). Verbal fluency declined after left (p = 0.013) but increased after right STN DBS (p < 0.001), and response inhibition was faster following right STN DBS (p = 0.031). Regardless of hemisphere, delayed recall declined modestly over time versus baseline (p = 0.001), and immediate recall was unchanged. INTERPRETATION: Directional versus ring STN DBS did not differentially affect cognition. Similar to prior bilateral DBS studies, unilateral left stimulation worsened verbal fluency performance. In contrast, unilateral right STN surgery increased performance on verbal fluency and response inhibition tasks. Our findings raise the hypothesis that unilateral right STN DBS in selected patients with predominant right brain motor parkinsonism could mitigate declines in verbal fluency associated with the bilateral intervention. ANN NEUROL 2024;95:1205-1219.

Cognitive Dysfunction in Non-CNS Metastatic Cancer: Comparing Brain Metastasis, Non-CNS Metastasis, and Healthy Controls.

Limited research has compared cognition of people with non-central nervous system metastatic cancer (NCM) vs. metastatic brain cancer (BM). This prospective cross-sectional study was comprised 37 healthy controls (HC), 40 NCM, and 61 BM completing 10 neuropsychological tests. The NCM performed below HCs on processing speed and executive functioning tasks, while the BM group demonstrated lower performance across tests. Tasks of processing speed, verbal fluency, and verbal memory differentiated the clinical groups (BM < NCM). Nearly 20% of the NCM group was impaired on at least three neuropsychological tests whereas approximately 40% of the BM group demonstrated the same level of impairment.

Neuropsychological Functioning in Primary Dystonia: Updated and Expanded Multidomain Meta-Analysis.

BACKGROUND: Primary dystonia is conventionally considered as a motor disorder, though an emerging literature reports associated cognitive dysfunction. OBJECTIVES: Here, we conducted meta-analyses on studies comparing clinical measures of cognition in persons with primary dystonia and healthy controls (HCs). METHODS: We searched PubMed, Embase, Cochrane Library, Scopus, and PsycINFO (January 2000-October 2020). Analyses were modeled under random effects. We used Hedge's g as a bias-corrected estimate of effect size, where negative values indicate lower performance in dystonia versus controls. Between-study heterogeneity and bias were primarily assessed with Cochran's Q, I2 , and Egger's regression. RESULTS: From 866 initial results, 20 studies met criteria for analysis (dystonia n = 739, controls n = 643; 254 effect sizes extracted). Meta-analysis showed a significant combined effect size of primary dystonia across all studies (g = -0.56, P < 0.001), with low heterogeneity (Q = 25.26, P = 0.15, I2  = 24.78). Within-domain effects of primary dystonia were motor speed = -0.84, nonmotor speed = -0.83, global cognition = -0.65, language = -0.54, executive functioning = -0.53, learning/memory = -0.46, visuospatial/construction = -0.44, and simple/complex attention = -0.37 (P-values <0.01). High heterogeneity was observed in the motor/nonmotor speed and learning/memory domains. There was no evidence of publication bias. Moderator analyses were mostly negative but possibly underpowered. Blepharospasm samples showed worse performance than other focal/cervical dystonias. Those with inherited (ie, genetic) disease etiology demonstrated worse performance than acquired. CONCLUSIONS: Dystonia patients consistently demonstrated lower performances on neuropsychological tests versus HCs. Effect sizes were generally moderate in strength, clustering around -0.50 SD units. Within the speed domain, results suggested cognitive slowing beyond effects from motor symptoms. Overall, findings indicate dystonia patients experience multidomain cognitive difficulties, as detected by neuropsychological tests. © 2022 International Parkinson and Movement Disorder Society.

Developmental innervation of cranial dura mater and migraine headache: A narrative literature review.

INTRODUCTION: Migraine headache prevalence, etiology, and clinical presentations change from childhood to adulthood. Dural innervation plays a role in headache symptomatology, but the changes in innervation during development have not been fully explored in the literature. METHODS: A narrative literature review on developmental innervation of cranial dura mater in the context of migraine headache. RESULTS: Dural structures, nerve distributions, and pain attributed to migraine headache at varying stages of development are discussed herein with a focus on clinical findings and presentations. CONCLUSIONS: There are many differences in migraine presentation throughout development. Notably, the nervus spinosus and nervus tentorii may play a role in developmental differences in migraine headache presentations between children and adults.

Clinical correlates of the ability to consent to research participation in brain metastasis.

OBJECTIVE: Impairment in the ability to provide informed consent is common in persons with brain metastasis. However, little is known about what factors contribute to this impairment in the patient group. Our objective is to determine if the associations between demographic, cognitive, and clinical variables correlate with the ability to provide informed consent in persons with brain metastasis. METHODS: We administered a comprehensive neuropsychological battery to a group of 61 persons with brain metastasis. Demographic and clinical information was also collected. All diagnoses were made by board-certified oncologists and were verified histologically. Statistical analyses included Pearson's product-moment correlations, point biserial correlations, and linear regression. RESULTS: Results indicated that combinations of education, verbal memory, executive function, whole brain radiation therapy, and chemotherapy affected various aspects of the ability to provide informed consent. Subsequent regression models demonstrated that these variables contributed a significant amount of shared variance to the ability to provide informed consent. CONCLUSION: We found that the ability of persons with brain metastasis to provide informed consent is a cognitively complex ability that is also affected by education and treatment variables. This information can help clinical researchers in identifying persons with brain metastasis at risk of an impaired ability to provide informed consent and aid in the consenting process.

Using cognition to predict the ability to understand medical treatment in brain and metastatic cancer.

OBJECTIVE: To determine if cognition can be used to identify persons with cancer at high risk for the impaired ability to understand treatment decisions. METHODS: The association between understanding treatment decisions and cognition was examined using data from 181 participants across four groups: 67 with brain metastasis, 41 with metastatic cancer that has not spread to the brain, 27 with malignant glioma, and 46 healthy controls. All diagnoses were made by board-certified oncologists and were verified histologically. RESULTS: Results indicated that numerous cognitive functions were associated with the ability to understand treatment decisions in persons with cancer. The following proportion of participants demonstrated impaired understanding of treatment decisions in our three patient groups: approximately 51% malignant glioma, approximately 46% brain metastasis, and approximately 24% metastatic cancer. In a combined brain cancer group, we were able to use cognitive performance to predict the impaired ability to understand treatment decisions. CONCLUSIONS: An impaired ability to understand treatment decisions is prevalent in persons with brain cancer and persons with metastatic cancer. Performance on a brief cognitive battery can be used to help clinicians identify patients at particular risk for impaired medical decision making.

Relationship between cognitive functioning, mood, and other patient factors on quality of life in metastatic brain cancer.

OBJECTIVE: Neurocognitive functioning (NCF), mood disturbances, physical functioning, and social support all share a relationship with health-related quality of life (HRQOL). However, investigations into these relationships have not been conducted in persons with brain metastases (BM). PATIENTS AND METHODS: Ninety-three newly diagnosed persons with BM were administered various cognitive batteries. Data were collected across a wide range of categories (ie, cognitive, demographic, disease/treatment, mood, social support, physical functioning). The Functional Assessment of Cancer Treatment (FACT) scale was used to measure HRQOL. RESULTS: Mood and physical function correlated with lower HRQOL in every measured domain. Verbal learning and memory correlated with every FACT subscale except emotional quality of life. Social support also correlated with several HRQOL domains. Stepwise linear regression revealed that mood predicted general well-being and several FACT subscales, including physical, emotional and cognitive well-being. Social support and physical health were predictive of general well-being. Verbal learning and memory predicted cognitive well-being. CONCLUSION: HRQOL is a complex construct affected by numerous variables. In particular, mood, physical functioning, and learning and memory were important predictors of HRQOL, and clinicians are encouraged to obtain information in these areas during baseline assessments in persons with BM.

Reappraisal of the anatomy of the frontotemporal branches of the facial nerve.

OBJECTIVE: The anatomy of the temporal branches of the facial nerve (FN) has been widely described in the neurosurgical literature because of its relevance in anterolateral approaches to the skull base and implication in frontalis palsies from these approaches. In this study, the authors attempted to describe the anatomy of the temporal branches of the FN and identify whether there are any FN branches that cross the interfascial space of the superficial and deep leaflets of the temporalis fascia. METHODS: The surgical anatomy of the temporal branches of the FN was studied bilaterally in 5 embalmed heads (n = 10 extracranial FNs). Exquisite dissections were performed to preserve the relationships of the branches of the FN and their relationship to the surrounding fascia of the temporalis muscle, the interfascial fat pad, the surrounding nerve branches, and their final terminal endpoints near the frontalis and temporalis muscles. The authors correlated their findings intraoperatively with 6 consecutive patients with interfascial dissection in which neuromonitoring was performed to stimulate the FN and associated twigs that were observed to be interfascial in 2 of them. RESULTS: The temporal branches of the FN stay predominantly superficial to the superficial leaflet of the temporal fascia in the loose areolar tissue near the superficial fat pad. As they course over the frontotemporal region, they give off a twig that anastomoses with the zygomaticotemporal branch of the trigeminal nerve, which crosses the superficial layer of the temporalis muscle, spanning the interfascial fat pad, and then pierces the deep temporalis fascial layer. This anatomy was observed in 10 of the 10 FNs dissected. Intraoperatively, stimulation of this interfascial segment yielded no facial muscle response up to 1 mA in any of the patients. CONCLUSIONS: The temporal branch of the FN gives off a twig that anastomoses with the zygomaticotemporal nerve, which crosses the superficial and deep leaflets of the temporal fascia. Interfascial surgical techniques aimed at protecting the frontalis branch of the FN are safe in their efforts to protect against frontalis palsy with no clinical sequelae when executed properly.

Differential cognitive effects of unilateral left and right subthalamic nucleus deep brain stimulation for Parkinson disease.

Objective: To investigate hemispheric effects of directional versus ring subthalamic nucleus (STN) deep brain stimulation (DBS) surgery on cognitive function in patients with advanced Parkinson's disease (PD). Methods: We examined 31 PD patients (Left STN n = 17; Right STN n = 14) who underwent unilateral subthalamic nucleus (STN) DBS as part of a NIH-sponsored randomized, cross-over, double-blind (ring vs directional) clinical trial. Outcome measures were tests of verbal fluency, auditory-verbal memory, and response inhibition. First, all participants were pooled together to study the effects of directional versus ring stimulation. Then, we stratified the groups by surgery hemisphere and studied the longitudinal changes in cognition post-unilateral STN DBS. Results: Relative to pre-DBS cognitive baseline performances, there were no group changes in cognition following unilateral DBS for either directional or ring stimulation. However, assessment of unilateral DBS by hemisphere revealed a different pattern. The left STN DBS group had lower verbal fluency than the right STN group (t(20.66 = -2.50, p = 0.02). Over a period of eight months post-DBS, verbal fluency declined in the left STN DBS group (p = 0.013) and improved in the right STN DBS group over time (p < .001). Similarly, response inhibition improved following right STN DBS (p = 0.031). Immediate recall did not significantly differ over time, nor was it affected by implant hemisphere, but delayed recall equivalently declined over time for both left and right STN DBS groups (left STN DBS p = 0.001, right STN DBS differ from left STN DBS p = 0.794). Conclusions: Directional and ring DBS did not differentially or adversely affect cognition over time. Regarding hemisphere effects, verbal fluency decline was observed in those who received left STN DBS, along with the left and right STN DBS declines in delayed memory. The left STN DBS verbal fluency decrement is consistent with prior bilateral DBS research, likely reflecting disruption of the basal-ganglia-thalamocortical network connecting STN and inferior frontal gyrus. Interestingly, we found an improvement in verbal fluency and response inhibition following right STN DBS. It is possible that unilateral STN DBS, particularly in the right hemisphere, may mitigate cognitive decline.

Resection of Brainstem Arteriovenous Malformations: Pearls and Pitfalls for Minimizing Complications.

BACKGROUND: The decision-making process surrounding resection of arteriovenous malformations (AVMs) in proximity to vital brainstem structures is a complex topic. Intricate vasculature in the setting of exquisite brainstem eloquence creates a high-risk operative landscape with the potential for devastating complications. Effective resections are driven by mastery of the relevant operative anatomy, preservation of pertinent vasculature, and technical experience and acumen. METHODS: This article provides a narrative literature review on the resection of brainstem AVMs. RESULTS: Operative anatomy and approaches to AVMs of the midbrain (anterior/posterior), pons (anterior/lateral), and medulla (anterior/lateral) are discussed herein, with a focus on pearls and pitfalls for minimizing complications during resection. CONCLUSIONS: Careful consideration of the patient's clinical background, the natural history of the lesion, and expertise of the treating surgeon are paramount for improving the natural course of brainstem AVMs.

Resection of Brainstem Cavernous Malformations: Pearls and Pitfalls for Minimizing Complications.

BACKGROUND: Surgical management of brainstem cavernous malformations (CMs) is a controversial topic in the field of neurosurgery. These lesions have a propensity to hemorrhage, thereby disrupting surrounding brainstem eloquence. METHODS: This article provides the personal reflections of the senior author and a narrative literature review on resection of brainstem CMs. RESULTS: Here we discuss the indications for microsurgery, microsurgical techniques and nuances, and perioperative management considerations necessary to minimize complications during resection of brainstem CMs, which are lesions of venous origin. CONCLUSIONS: The natural history of the lesion, risk of future hemorrhage, and potential for symptom resolution should be carefully considered when planning to resect brainstem CMs. Nuanced microsurgical techniques with minimal disruption of normal tissues provide the best chance of satisfactory outcomes.

Leveraging the Power of the Internet for Neurosurgical Education: A Standardized Survey for the Pursuit of Educational Excellence.

OBJECTIVE: Our goal was to investigate the presence of surveys to assess neurosurgical educational content and to propose a novel standardized Neurosurgical Education Outcomes Survey (NEOS) with compatible statistical analyses. METHODS: Google Scholar and PubMed were used to conduct a structured literature review for articles published between January 2000 and July 2021 and containing standardized methodology for assessing neurosurgical educational content. RESULTS: Fifteen studies identified during the search assessed virtual and in-person educational content; however, the literature lacked a standardized assessment. A standardized NEOS was proposed before a comprehensive discussion of compatible statistical analyses. CONCLUSIONS: The NEOS may offer a viable option for comparing in-person and virtual content with respect to learner preferences and subjective and objective feedback. Future studies are needed to explore practical utility in enhancing the quality of neurosurgical educational content.

Magnesium Levels and Diastolic Blood Pressure (DBP) as a Vasospasm Prediction Metric in Patients With Aneurysmal Subarachnoid Hemorrhage (SAH).

Introduction Vasospasm is a significant cause of morbidity and mortality in patients with aneurysmal subarachnoid hemorrhage (SAH). The purpose of this study is to evaluate a possible link between vasospasm in patients with aneurysmal SAH and magnesium and blood pressure levels. Methods Subjects were selected based on chart review of patients presenting to a comprehensive stroke center in Southern California with aneurysmal SAH. 27 were included based on the following criteria: patients greater than 18 years of age, aneurysmal SAH, clinically symptomatic vasospasms and at least one diagnostic confirmation - either from a transcranial doppler (TCD) or digital subtraction angiogram (DSA). The following exclusion criteria also applied: 1) incomplete documentation in the medical record; 2) patients <18 years of age; and 3) patients without TCD measurements. Results In an overall analysis of all patients with or without vasospasm, it was found that the presence of vasospasm was significantly correlated with diastolic blood pressures (DBPs) on day of vasospasm with an r value of 0.418 and p<0.001. Average daily DBPs throughout hospital stay were also correlated with vasospasm with an r-value of 0.455 and p<0.001. Changes in magnesium overall were also significantly related to left Lindegaard ratios with an r value of -0.201 and p value of 0.032. Lindegaard ratios were significantly correlated with age with r values of 0.510, p<0.001, and r=-0.482, p<0.001 for left and right, respectively. A change in magnesium was inversely correlated to the left Lindegaard ratio with an n of 31 and p value of 0.014 (r= -0.439) in patients with vasospasm. We also found a lower incidence of vasospasm in patients older than 65. Conclusion Monitoring magnesium and increases in DBP might be effective as a prophylactic adjunct method in patients with SAH in an effort to predict clinical vasospasm.

Do social determinants of health impact access to neurosurgical care in the United States? A workforce perspective.

OBJECTIVE: This study attempts to use neurosurgical workforce distribution to uncover the social determinants of health that are associated with disparate access to neurosurgical care. METHODS: Data were compiled from public sources and aggregated at the county level. Socioeconomic data were provided by the Brookings Institute. Racial and ethnicity data were gathered from the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research. Physician density was retrieved from the Health Resources and Services Administration Area Health Resources Files. Catchment areas were constructed based on the 628 counties with neurosurgical coverage, with counties lacking neurosurgical coverage being integrated with the nearest covered county based on distances from the National Bureau of Economic Research's County Distance Database. Catchment areas form a mutually exclusive and collectively exhaustive breakdown of the entire US population and licensed neurosurgeons. Socioeconomic factors, race, and ethnicity were chosen as independent variables for analysis. Characteristics for each catchment area were calculated as the population-weighted average across all contained counties. Linear regression analysis modeled two outcomes of interest: neurosurgeon density per capita and average distance to neurosurgical care. Coefficient estimates (CEs) and 95% confidence intervals were calculated and scaled by 1 SD to allow for comparison between variables. RESULTS: Catchment areas with higher poverty (CE = 0.64, 95% CI 0.34-0.93) and higher prime age employment (CE = 0.58, 95% CI 0.40-0.76) were significantly associated with greater neurosurgeon density. Among categories of race and ethnicity, catchment areas with higher proportions of Black residents (CE = 0.21, 95% CI 0.06-0.35) were associated with greater neurosurgeon density. Meanwhile, catchment areas with higher proportions of Hispanic residents displayed lower neurosurgeon density (CE = -0.17, 95% CI -0.30 to -0.03). Residents of catchment areas with higher housing vacancy rates (CE = 2.37, 95% CI 1.31-3.43), higher proportions of Native American residents (CE = 4.97, 95% CI 3.99-5.95), and higher proportions of Hispanic residents (CE = 2.31, 95% CI 1.26-3.37) must travel farther, on average, to receive neurosurgical care, whereas people living in areas with a lower income (CE = -2.28, 95% CI -4.48 to -0.09) or higher proportion of Black residents (CE = -3.81, 95% CI -4.93 to -2.68) travel a shorter distance. CONCLUSIONS: Multiple factors demonstrate a significant correlation with neurosurgical workforce distribution in the US, most notably with Hispanic and Native American populations being associated with greater distances to care. Additionally, higher proportions of Hispanic residents correlated with fewer neurosurgeons per capita. These findings highlight the interwoven associations among socioeconomics, race, ethnicity, and access to neurosurgical care nationwide.

Steroid-Resistant Double-Seronegative Optic Neuritis Responds Favorably to Plasma Exchange.

The clinical presentation of optic neuritis is quite characteristic, and the epidemiology, differential diagnosis, and treatment protocol are well established. However, when the presentation of optic neuritis is atypical, bilateral, and intravenous steroid-resistant, the treatment guidelines are quite nebulous. We present a case of bilateral severe double-seronegative optic neuritis with catastrophic vision loss and intravenous steroid resistance. After an exhaustive investigation, we empirically treated our patient with plasma exchange therapy and obtained a dramatic recovery of vision. When an immune etiology is suspected, this case is instructive vis-a-vis the utility of plasma exchange in refractory cases of optic neuritis despite seronegativity.

Isolated Double-Positive Optic Neuritis: A Case of Aquaporin-4 and Myelin Oligodendrocyte Glycoprotein Antibody Seropositivity.

Optic neuritis (ON) causes acute vision loss with typical and atypical profiles, serological markers, imaging findings, and clinical outcomes depending on the associated underlying pathophysiology. Neuromyelitis optica (NMO) and myelin oligodendrocyte glycoprotein antibody disease (MOGAD) are the usual causes of acute severe sequential or simultaneous bilateral optic neuritis. These conditions are usually accompanied by multi-level spinal cord demyelination, and notably, they are typically positive for either NMO or Myelin oligodendrocyte glycoprotein (MOG) autoantibodies, but rarely both. We present a case of isolated sequential bilateral optic neuritis that was seropositive for both NMO and MOG antibodies.

Atypical Neuroleptic Malignant Syndrome in the Setting of Quetiapine Overdose: A Case Report and Review of the Literature.

Neuroleptic malignant syndrome (NMS) is a rare and life-threatening emergency. The condition is largely iatrogenic and is often precipitated by medications such as antipsychotics. First-generation antipsychotics are more likely to cause NMS than second-generation antipsychotics. The literature lacks an objective measure for NMS diagnosis. Instead, the diagnosis relies largely on the recognition of characteristic symptoms in the presence of an inciting medication. Additional challenges exist with concomitant disease processes and toxicities that may distort the clinical picture. Here, we report a case of a 44-year-old Caucasian man who presented with atypical NMS in the setting of quetiapine overdose. The patient remained uncharacteristically afebrile throughout his admission. Although the patient recovered, extended delays in identification and management can contribute to an increased risk of morbidity and mortality.

Malignant lymphomatous invasion of Meckel's cave: pathoanatomical considerations of the petrous apex.

Secondary central nervous system lymphoma is rare, occurring in up to 10% of non-Hodgkin's lymphoma patients and in 5% of diffuse large B-cell lymphoma patients. The prognosis is poor, even rarer is metastasis of large B-cell lymphomas into Meckel's cave and the trigeminal nerve roots. We describe a relapsing case of a large B-cell lymphoma that migrated into Meckel's cave, the mandibular branch of the trigeminal nerve and the adjacent cavernous sinus. We review petrous apex anatomy, review the literature of metastatic spread into Meckel's cave and analyse existing pathoanatomical studies that explain the conduits and barriers of tumour spread. Understanding this pathoanatomical relationship is critical for neurologists and neurosurgeons alike to effectively correlate patient signs and symptoms to intracranial pathology and identify origins and sites of metastatic dispersion in similar rare clinical scenarios.

Myeloneuropathy in the Setting of Hypocupremia: An Overview of Copper-Related Pathophysiology.

A posterior cord or dorsal column myelopathy due to neurosyphilis presenting as a tabetic gait is a classic neurological vignette and is taught to all medical students. Its clinical presentation is so graphic that its simulacrum with diseases other than neurosyphilis is labeled as pseudotabes. The latter can be seen with vitamin B12 deficiency as a subacute combined degeneration (SCD) of the spinal cord, another neurology classic. However, not all cases of pseudotabes are due to posterior cord myelopathy as some can arise with other deafferentation syndromes such as polyganglioneuropathies as seen with paraneoplastic syndromes, Sjogren's syndrome, idiopathic autoimmune diseases, and post-viral neuronopathies. A unique and interesting cause of pseudotabes is due to copper deficiency; copper being a metallic trace element that is fundamental to cellular life. Herein, we present a case of copper deficiency manifesting as pseudotabes and review the biochemical properties of copper and its effects on the nervous system.

Nonmissile penetrating head injury with a wooden table leg: An illustrative case.

Penetrating head injuries are relatively uncommon and require a unique approach. This report highlights a previously unreported mechanism of injury with a table leg and the steps required to evaluate and promptly treat the patient.