Deep brain stimulation of the amygdala for treatment-resistant combat post-traumatic stress disorder: Long-term results.

Deep brain stimulation (DBS) holds promise for neuropsychiatric conditions where imbalance in network activity contributes to symptoms. Treatment-resistant Combat post-traumatic stress disorder (TR-PTSD) is a highly morbid condition and 50% of PTSD sufferers fail to recover despite psychotherapy or pharmacotherapy. Reminder-triggered symptoms may arise from inadequate top-down ventromedial prefrontal cortex (vmPFC) control of amygdala reactivity. Here, we report long-term data on two TR-PTSD participants from an investigation utilizing high-frequency amygdala DBS. The two combat veterans were implanted bilaterally with quadripolar electrodes targeting the basolateral amygdala. Following a randomized staggered onset, patients received stimulation with adjustments based on PTSD symptom severity for four years while psychiatric and neuropsychiatric symptoms, neuropsychological performance, and electroencephalography were systematically monitored. Evaluation of vmPFC-Amygdala network engagement was assessed with 18FDG positron emission tomography (PET). CAPS-IV scores varied over time, but improved 55% from 119 at baseline to 53 at 4-year study endpoint in participant 1; and 44%, from 68 to 38 in participant 2. Thereafter, during 5 and 1.5 years of subsequent clinical care respectively, long-term bilateral amygdala DBS was associated with additional, clinically significant symptomatic and functional improvement. There were no serious stimulation-related adverse psychiatric, neuropsychiatric, neuropsychological, neurological, or neurosurgical effects. In one subject, symptomatic improvement was associated with an intensity-dependent reduction in amygdala theta frequency power. In our two participants, FDG-PET findings were inconclusive regarding the hypothesized mechanism of suppression of amygdala hyperactivity. Our findings encourage further research to confirm and extend our preliminary observations.

The effect of older age on outcomes of rTMS treatment for treatment-resistant depression.

Clinical outcomes of repetitive transcranial magnetic stimulation (rTMS) for treatment of treatment-resistant depression (TRD) vary widely and there is no mood rating scale that is standard for assessing rTMS outcome. It remains unclear whether TMS is as efficacious in older adults with late-life depression (LLD) compared to younger adults with major depressive disorder (MDD). This study examined the effect of age on outcomes of rTMS treatment of adults with TRD. Self-report and observer mood ratings were measured weekly in 687 subjects ages 16-100 years undergoing rTMS treatment using the Inventory of Depressive Symptomatology 30-item Self-Report (IDS-SR), Patient Health Questionnaire 9-item (PHQ), Profile of Mood States 30-item, and Hamilton Depression Rating Scale 17-item (HDRS). All rating scales detected significant improvement with treatment; response and remission rates varied by scale but not by age (response/remission ≥ 60: 38%-57%/25%-33%; <60: 32%-49%/18%-25%). Proportional hazards models showed early improvement predicted later improvement across ages, though early improvements in PHQ and HDRS were more predictive of remission in those < 60 years (relative to those ≥ 60) and greater baseline IDS burden was more predictive of non-remission in those ≥ 60 years (relative to those < 60). These results indicate there is no significant effect of age on treatment outcomes in rTMS for TRD, though rating instruments may differ in assessment of symptom burden between younger and older adults during treatment.

Bilateral Cerebellar Repetitive Transcranial Magnetic Stimulation for Chronic Ataxia After Hemorrhagic Stroke: a Case Report.

There are insufficient treatment options available for recovery related to cerebellar ataxia. Limited data using repetitive transcranial magnetic stimulation (rTMS) have demonstrated reduction of symptom burden, though associated with nonuniform cerebellar ataxia etiologies and differing rTMS treatment protocols. Additionally, there are limited available data for use of rTMS in individuals suffering from stroke-related symptoms. We present the case of a patient with chronic cerebellar ataxia following a hemorrhagic stroke who underwent inhibitory rTMS to bilateral cerebellar targets with demonstrated improvement in symptoms.

Evolution of flash visual evoked potentials to monitor visual pathway integrity during tumor resection: illustrative cases and literature review.

Flash visual evoked potentials (fVEPs) provide a means to interrogate visual system functioning intraoperatively during tumor resection in which the optic pathway is at risk for injury. Due to technical limitations, fVEPs have remained underutilized in the armamentarium of intraoperative neurophysiological monitoring (IONM) techniques. Here we review the evolution of fVEPs as an IONM technique with emphasis on the enabling technological and intraoperative improvements. A combined approach with electroretinography (ERG) has enhanced feasibility of fVEP neuromonitoring as a practical application to increase safety and reduce error during tumor resection near the prechiasmal optic pathway. The major advance has been towards differentiating true cases of damage from false findings. We use two illustrative neurosurgical cases in which fVEPs were monitored with and without ERG to discuss limitations and demonstrate how ERG data can clarify false-positive findings in the operating room. Standardization measures have focused on uniformity of photostimulation parameters for fVEP recordings between neurosurgical groups.

Stimulated Raman histology facilitates accurate diagnosis in neurosurgical patients: a one-to-one noninferiority study.

OBJECTIVE: Stimulated Raman histology (SRH) offers efficient and accurate intraoperative neuropathological tissue analysis without procedural alteration to the diagnostic specimen. However, there are limited data demonstrating one-to-one tissue comparisons between SRH and traditional frozen sectioning. This study explores the non-inferiority of SRH as compared to frozen section on the same piece of tissue in neurosurgical patients. METHODS: Tissue was collected over a 1-month period from 18 patients who underwent resection of central nervous system lesions. SRH and frozen section analyses were compared for diagnostic capabilities as well as assessed for quality and condition of tissue via a survey completed by pathologists. RESULTS: SRH was sufficient for diagnosis in 78% of specimens as compared to 94% of specimens by frozen section of the same specimen. A Fisher's exact test determined there was no significant difference in diagnostic capability between the two groups. Additionally, both quality of SRH and condition of tissue after SRH were deemed to be non-inferior to frozen section. CONCLUSIONS: This study provides further evidence for the non-inferiority of SRH techniques. It is also the first study to demonstrate SRH accuracy using one-to-one tissue analysis in neuropathological specimens.

Transcranial magnetic stimulation for post-operative neurorehabilitation in neuro-oncology: a review of the literature and future directions.

INTRODUCTION: Transcranial magnetic stimulation (TMS) is a neuromodulation technology capable of targeted stimulation and inhibition of cortical areas. Repetitive TMS (rTMS) has demonstrated efficacy in the treatment of several neuropsychiatric disorders, and novel uses of rTMS for neurorehabilitation in patients with acute and chronic neurologic deficits are being investigated. However, studies to date have primarily focused on neurorehabilitation in stroke patients, with little data supporting its use for neurorehabilitation in brain tumor patients. METHODS: We performed a review of the current available literature regarding uses of rTMS for neurorehabilitation in post-operative neuro-oncologic patients. RESULTS: Data have demonstrated that rTMS is safe in the post-operative neuro-oncologic patient population, with minimal adverse effects and no documented seizures. The current evidence also demonstrates potential effectiveness in terms of neurorehabilitation of motor and language deficits. CONCLUSIONS: Although data are overall limited, both safety and effectiveness have been demonstrated for the use of rTMS for neurorehabilitation in the neuro-oncologic population. More randomized controlled trials and specific comparisons of contralateral versus ipsilateral rTMS protocols should be explored. Further work may also focus on individualized, patient-specific TMS treatment protocols for optimal functional recovery.

New-Onset Neurologic Symptoms and Related Neuro-Oncologic Lesions Discovered After COVID-19 Vaccination: Two Neurosurgical Cases and Review of Post-Vaccine Inflammatory Responses.

A global effort is underway to distribute coronavirus disease 2019 (COVID-19) vaccines to limit the crisis. Although adverse events related to vaccination are rare, there have been cases of new-onset neurologic symptoms following vaccination. We present two cases of new-onset neurologic symptoms post-vaccination that, upon further workup, revealed two different neuro-oncologic processes requiring neurosurgical intervention and further treatment. We hypothesize that despite these processes being unrelated to vaccination, the COVID-19 vaccines may induce an inflammatory cascade with the ability to uncover underlying sinister pathology. Our report therefore emphasizes the need for careful evaluation in the setting of new-onset neurologic symptoms after COVID-19 vaccination.

Large Adult Spinal Diffuse Midline Histone H3 Lysine27-to-Methionine-Mutant Glioma With Intramedullary and Extramedullary Components Presenting With Progressive Hydrocephalus: A Case Report Highlighting Unique Imaging Findings and Treatment.

Diffuse midline glioma with histone H3 lysine27-to-methionine mutation (H3 K27M mutation) is a rare, aggressive tumor that is designated as World Health Organization (WHO) grade IV regardless of histologic features. Preoperative diagnosis remains challenging due to limited evidence regarding distinctive clinical and imaging characteristics. We describe the case of a young woman who presented with progressively worsening headaches due to communicating hydrocephalus. MR imaging with contrast of the cervical and thoracic spine revealed diffuse leptomeningeal enhancement with focal areas of intramedullary and subarachnoid T2 hyperintensity and enhancement, suggestive of a potential infectious process. Intraoperatively, no epidural pathology was identified, and with the differential diagnosis remaining broad, a second procedure was conducted involving intradural exploration and biopsy of a lesion. This was then identified as a diffuse midline glioma with H3 K27M mutation. The nonfocal clinical presentation in the setting of communicating hydrocephalus as well as the significant exophytic tumor growth and imaging findings made the initial diagnosis unique and challenging. This case, therefore, emphasizes the rare presentation of this tumor, and the need for further understanding of the clinical and imaging characteristics of this disease as well as the need for effective therapeutics.

Multiple Brain Abscesses Due to Nocardia otitidiscaviarum: Case Report and Treatment Implications.

Nocardia infections typically present in immunocompromised hosts. Brain abscesses caused by species such as Nocardia  asteroides, farcinica, and abscessus are well-documented in the literature. We present a rare case of an immunocompetent patient with multiple brain abscesses due to Nocardia otitidiscaviarum requiring a decompressive fronto-temporoparietal craniectomy due to symptomatic intracranial hypertension. The patient was treated with intrathecal amikacin in addition to standard antibiotics with the resolution of the disease and good neurologic outcome. This is one of few case reports overall involving this species within the brain, and the second to report favorable outcomes. This case describes implications for treatment and adds to sparse literature regarding this particular pathogen.

Synthetic cannabinoid-associated coagulopathy secondary to long-acting anticoagulant rodenticides: Observational case series and management recommendations.

Synthetic cannabinoids have become increasingly popular drugs of abuse due to low cost and inability to detect these substances on routine drug screenings. In the United States, incidence of synthetic cannabinoid contamination with long-acting anticoagulant rodenticides (LAARs) resulting in coagulopathy and bleeding complications has been described.We sought to describe the natural history, management approach, and outcomes of bleeding secondary to synthetic cannabinoid-associated LAAR toxicity in an observational case series of patients evaluated at an urban academic medical system.We conducted an observational study of patients with suspected exposure to LAAR-contaminated synthetic cannabinoids and associated bleeding treated within the Johns Hopkins Health System.In this 16 subject cohort, hematuria was the most common bleeding symptom at presentation. The majority of the cohort (75%) had international normalized ratio (INR) > 9.6 at presentation. Of the 13 patients with brodifacoum testing, 12/13 (92%) were positive. Twelve patients (75%) had at least 1 INR value below 2 within 24 hours of the first INR measurement. Of this cohort, 1/16 (6%) died in hospital. The median length of hospital stay was 4 days, (interquartile range = 3-6). The average cost of pharmacological treatment for coagulopathy during inpatient hospitalization was $5300 (range, $2241-$8086).In patients presenting with unexplained coagulopathy it is important for emergency department providers to consider LAAR intoxication and consider formal testing for brodifacoum to assist with treatment planning. Use of a standardized management algorithm including intravenous/oral vitamin K, judicious use of blood products and close laboratory monitoring is essential to optimizing outcomes.

What Influences Mental Illness? Discrepancies Between Medical Education and Conception.

OBJECTIVE: This preliminary study examined the differences between what was taught during a formal medical education and medical students' and psychiatry residents' conceptions of notions regarding the causes and determinants of mental illness. METHODS: The authors surveyed 74 medical students and 11 residents via convenience sampling. The survey contained 18 statements which were rated twice based on truthfulness in terms of a participant's formal education and conception, respectively. Descriptive statistics and a Wilcoxon signed rank test determined differences between education and conception. RESULTS: Results showed that students were less likely to perceive a neurotransmitter imbalance to cause mental illness, as opposed to what was emphasized during a formal medical education. Students and residents also understood the importance of factors such as systemic racism and socioeconomic status in the development of mental illness, which were factors that did not receive heavy emphasis during medical education. Furthermore, students and residents believed that not only did mental illnesses have nonuniform pathologies, but that the Diagnostic and Statistical Manual of Mental Disorders also had the propensity to sometimes arbitrarily categorize individuals with potentially negative consequences. CONCLUSIONS: If these notions are therefore part of students' and residents' conceptions, as well as documented in the literature, then it seems appropriate for medical education to be further developed to emphasize these ideas.

Anomalous Origin of the Left Vertebral Artery from the Aortic Arch.

Anatomic anomalies of the aortic arch have implications for clinical practice if their significance is understood. Our case study involves a cadaveric finding of the left vertebral artery originating directly from the aortic arch. Although this anatomical variation has been documented, the prevalence of this anomaly may be generally underestimated. After noting this anomaly, we analyzed 27 cases and found that four female cadavers had the left vertebral artery originating from the aortic arch rather than the left subclavian artery. With a prevalence rate of 14.8%, it would seem that this anomaly is more significant than previously thought, which could have implications for surgical practice.