Causal network localization of brain stimulation targets for trait anxiety.

Transcranial magnetic stimulation (TMS) and deep brain stimulation (DBS) can treat some neuropsychiatric disorders, but there is no consensus approach for identifying new targets. We localized causal circuit-based targets for anxiety that converged across multiple natural experiments. Lesions (n=451) and TMS sites (n=111) that modify anxiety mapped to a common normative brain circuit (r=0.68, p=0.01). In an independent dataset (n=300), individualized TMS site connectivity to this circuit predicted anxiety change (p=0.02). Subthalamic DBS sites overlapping the circuit caused more anxiety (n=74, p=0.006), thus demonstrating a network-level effect, as the circuit was derived without any subthalamic sites. The circuit was specific to trait versus state anxiety in datasets that measured both (p=0.003). Broadly, this illustrates a pathway for discovering novel circuit-based targets across neuropsychiatric disorders.

Resting State Functional Magnetic Resonance Imaging Elucidates Neurotransmitter Deficiency in Autism Spectrum Disorder.

Resting-state functional magnetic resonance imaging provides dynamic insight into the functional organization of the brains' intrinsic activity at rest. The emergence of resting-state functional magnetic resonance imaging in both the clinical and research settings may be attributed to recent advancements in statistical techniques, non-invasiveness and enhanced spatiotemporal resolution compared to other neuroimaging modalities, and the capability to identify and characterize deep brain structures and networks. In this report we describe a 16-year-old female patient with autism spectrum disorder who underwent resting-state functional magnetic resonance imaging due to late regression. Imaging revealed deactivated networks in deep brain structures involved in monoamine synthesis. Monoamine neurotransmitter deficits were confirmed by cerebrospinal fluid analysis. This case suggests that resting-state functional magnetic resonance imaging may have clinical utility as a non-invasive biomarker of central nervous system neurochemical alterations by measuring the function of neurotransmitter-driven networks. Use of this technology can accelerate and increase the accuracy of selecting appropriate therapeutic agents for patients with neurological and neurodevelopmental disorders.

Locked-in Intact Functional Networks in Children with Autism Spectrum Disorder: A Case-Control Study.

Resting-state functional magnetic resonance imaging (rs-fMRI) has the potential to investigate abnormalities in brain network structure and connectivity on an individual level in neurodevelopmental disorders, such as autism spectrum disorder (ASD), paving the way toward using this technology for a personalized, precision medicine approach to diagnosis and treatment. Using a case-control design, we compared five patients with severe regressive-type ASD to five patients with temporal lobe epilepsy (TLE) to examine the association between brain network characteristics and diagnosis. All children with ASD and TLE demonstrated intact motor, language, and frontoparietal (FP) networks. However, aberrant networks not usually seen in the typical brain were also found. These aberrant networks were located in the motor (40%), language (80%), and FP (100%) regions in children with ASD, while children with TLE only presented with aberrant networks in the motor (40%) and language (20%) regions, in addition to identified seizure onset zones. Fisher's exact test indicated a significant relationship between aberrant FP networks and diagnosis (p = 0.008), with ASD and atypical FP networks co-occurring more frequently than expected by chance. Despite severe cognitive delays, children with regressive-type ASD may demonstrate intact typical cortical network activation despite an inability to use these cognitive facilities. The functions of these intact cognitive networks may not be fully expressed, potentially because aberrant networks interfere with their long-range signaling, thus creating a unique "locked-in network" syndrome.

Microvascular Transposition Without Teflon: A Single Institution's 17-Year Experience Treating Trigeminal Neuralgia.

BACKGROUND: Trigeminal neuralgia (TN) refractory to medical management is often treated with microvascular decompression (MVD) involving the intracranial placement of Teflon. The placement of Teflon is an effective treatment, but does apply distributed pressure to the nerve and has been associated with pain recurrence. OBJECTIVE: To report the rate of postoperative pain recurrence in TN patients who underwent MVD surgery using a transposition technique with fibrin glue without Teflon. METHODS: Patients were eligible for our study if they were diagnosed with TN, did not have multiple sclerosis, and had an offending vessel that was identified and transposed with fibrin glue at our institution. All eligible patients were given a follow-up survey. We used a Kaplan-Meier (KM) model to estimate overall pain recurrence. RESULTS: A total of 102 patients met inclusion criteria, of which 85 (83%) responded to our survey. Overall, 76 (89.4%) participants responded as having no pain recurrence. Approximately 1-yr pain-free KM estimates were 94.1% (n = 83), 5-yr pain-free KM estimates were 94.1% (n = 53), and 10-yr pain-free KM estimates were 83.0% (n = 23). CONCLUSION: Treatment for TN with an MVD transposition technique using fibrin glue may avoid some cases of pain recurrence. The percentage of patients in our cohort who remained pain free at a maximum of 17 yr follow-up is on the high end of pain-free rates reported by MVD studies using Teflon. These results indicate that a transposition technique that emphasizes removing any compression near the trigeminal nerve root provides long-term pain-free rates for patients with TN.

Identifying and Addressing Barriers to Systemic Thrombolysis for Acute Ischemic Stroke in the Inpatient Setting: A Quality Improvement Initiative.

OBJECTIVES: To identify barriers to inpatient alteplase administration and implement an interdisciplinary program to reduce time to systemic thrombolysis. PATIENTS AND METHODS: Compared with patients presenting to the emergency department with an acute ischemic stroke (AIS), inpatients are delayed in receiving alteplase for systemic thrombolysis. Institutional AIS metrics were extracted from the electronic medical records of patients presenting as an inpatient stroke alert. All patients who received alteplase for AIS were included in the analysis. A gap analysis was used to assess institutional deficiencies. An interdisciplinary intervention was initiated to address these deficiencies. Efficacy was measured with pre- and postintervention surveys and institutional AIS metric analysis. Statistical significance was determined using the Student t test. We identified 5 patients (mean age, 73 years; 100% (5/5) male; 80% (4/5) white) who met inclusion criteria for the preintervention period (January 1, 2017, to December 31, 2017) and 10 patients (mean age, 71 years; 50% male; 80% white) for the postintervention period (October 31, 2018, to July 1, 2020). RESULTS: We found barriers to rapid delivery of thrombolytic treatment to include alteplase availability and comfort with bedside reconstitution. Interdisciplinary intervention strategies consisted of stocking alteplase on additional floors as well as structured education and hands-on alteplase reconstitution simulations for resident physicians. The mean time from stroke alert to thrombolysis was shorter postintervention than preintervention (57.4 minutes vs 77.8 minutes; P=.03). CONCLUSION: A coordinated interdisciplinary approach is effective in reducing time to systemic thrombolysis in patients experiencing AIS in the inpatient setting. A similar program could be implemented at other institutions to improve AIS treatment.

Clinical Characteristics of Moyamoya Angiopathy in a Pediatric Cohort.

Moyamoya angiopathy is a rare cerebral vasculopathy characterized by a progressive stenosis of the terminal portion of the internal carotid arteries and the development of abnormal collateral vessels. Children with moyamoya angiopathy become symptomatic because of cerebral ischemic complications, and many patients eventually need revascularization. In most pediatric patients with this disease, the etiology is likely genetic. We aim to report clinical characteristics of a single-center cohort of pediatric patients with moyamoya. We performed a retrospective chart review of patients <18 years with angiographically confirmed moyamoya disease evaluated at our institution. An in-house text search tool, Advanced Cohort Explorer, was used to filter electronic medical records for patients with a diagnosis of moyamoya angiopathy from January 1999 to December 2018. The inclusion criteria were age <18 years at the time of onset of disease and a diagnosis confirmed at Mayo clinic. Fifty-one patients met the inclusion criteria. Fifty-five percent of our cohort were male, and the median age was 9 years. Three patients had a family history of moyamoya disease. Approximately half of our patients had bilateral disease. Sixteen patients had a genetic or chromosomal diagnosis (Down syndrome and NF1 being most common). Congenital anomalies like heart defects and renal dysplasia were also noted. This study is unique in that it was a large study on pediatric patients with moyamoya angiopathy. It also highlights the importance of considering genetic syndromes as an underlying cause when moyamoya angiopathy starts early in life.

Onyx embolization of skull base paragangliomas: a single-center experience.

BACKGROUND: Skull base paragangliomas are highly vascular tumors that are often embolized before surgical resection; however, the safety and efficacy of preoperative embolization using an ethylene vinyl alcohol copolymer (Onyx; Medtronic, Dublin, Republic of Ireland) in these tumors is unknown. This retrospective cohort study evaluated patient outcomes after preoperative embolization of skull base paragangliomas using Onyx. METHODS: We retrospectively analyzed data from all patients with skull base paragangliomas who underwent preoperative Onyx embolization at our institution (January 01, 2005-December 31, 2017). Patient, tumor, embolization, and outcomes data were extracted by reviewing inpatient and outpatient clinical and imaging records. RESULTS: Seven patients were studied (5/7 [71%] female), 6 with glomus jugulares and 1 with a glomus vagale. The median age was 52 years, and the most common presenting symptom was cranial neuropathy (6/7 [86%]). The tumor vascular supply was from the ascending pharyngeal artery in all 7 cases (100%) with additional feeders including the occipital artery in 5 (71%); internal carotid artery in 3 (43%); middle meningeal, vertebral, and internal maxillary artery each in 2 (29%); and posterior auricular artery in 1 (14%). The median postembolization tumor devascularization was 80% (range, 64-95%). The only postembolization complication was a facial palsy in 1 patient. CONCLUSION: Preoperative embolization with Onyx affords excellent devascularization for the majority of skull base paragangliomas, and it may facilitate resection of these hypervascular lesions. The advantages provided by Onyx with respect to penetration of intratumoral vessels must be weighed against the risk of cranial neuropathy.

Nonconvulsive status epilepticus secondary to acute porphyria crisis.

Both variegate and acute intermittent porphyria can manifest with various neurological symptoms. Although acute symptomatic seizures have been previously described, they are typically tonic-clonic and focal impaired awareness seizures. Convulsive status epilepticus and epilepsia partialis continua are rare and have been described on a case report basis. To our knowledge, there are no previously reported cases describing non-convulsive status epilepticus (NCSE) with electroencephalogram (EEG) documentation in the setting of acute porphyria crisis. We report a unique presentation of NCSE, which resolved after administering levetiracetam in a patient with variegate porphyria, without a known seizure disorder.

A Prognosis for Health Systems Science Courses: Observations From Current Students.

Certain medical schools have begun teaching courses in health systems science (HSS) to train medical students in skills aimed to improve health care in the United States. Although substantial research has been done on the potential benefit of HSS courses, reactions from students have not been reported. In this Invited Commentary, five medical students who have completed the first year of a longitudinal HSS course at the Arizona campus of the Mayo Clinic School of Medicine offer their observations of how early exposure to HSS affected their reactions to subsequent course work and current events in health care. The authors describe the HSS course and outline three benefits they have observed from their experience so far: (1) thinking more critically about health care delivery during all educational experiences, (2) gaining a better understanding of the complexity of the health care system, and (3) having a greater consideration for the many facets of health care delivery. The HSS course helped the authors identify health systems problems, develop solutions that incorporated diverse domains of health care delivery, and recognize the role and responsibility of the physician as an agent of change in a health care system.

Assessment of the Interrater Reliability of the Congress of Neurological Surgeons Microanastomosis Assessment Scale.

BACKGROUND: The potential for simulation-based learning in neurosurgical training has led the Congress of Neurosurgical Surgeons to develop a series of simulation modules. The Northwestern Objective Microanastomosis Assessment Tool (NOMAT) was created as the corresponding assessment tool for the Congress of Neurosurgical Surgeons Microanastomosis Module. The face and construct validity of the NOMAT have been previously established. OBJECTIVE: To further validate the NOMAT by determining its interrater reliability (IRR) between raters of varying levels of microsurgical expertise. METHODS: The NOMAT was used to assess residents' performance in a microanastomosis simulation module in 2 settings: Northwestern University and the Society of Neurological Surgeons 2014 Boot Camp at the University of Indiana. At Northwestern University, participants were scored by 2 experienced microsurgeons. At the University of Indiana, participants were scored by 2 postdoctoral fellows and an experienced microsurgeon. The IRR of NOMAT was estimated by computing the intraclass correlation coefficient using SPSS v22.0 (IBM, Armonk, New York). RESULTS: A total of 75 residents were assessed. At Northwestern University, 21 residents each performed microanastomosis on 2 model vessels of different sizes, one 3 mm and one 1 mm. At the University of Indiana, 54 residents performed a single microanastomosis procedure on 3-mm vessels. The intraclass correlation coefficient of the total NOMAT scores was 0.88 at Northwestern University and 0.78 at the University of Indiana. CONCLUSION: This study indicates high IRR for the NOMAT. These results suggest that the use of raters with varying levels of expertise does not compromise the precision or validity of the scale. This allows for a wider adoption of the scale and, hence, a greater potential educational impact.