Nociceptive neuropeptide increases and periorbital allodynia in a model of traumatic brain injury.

OBJECTIVE: This study tests the hypothesis that injury to the somatosensory cortex is associated with periorbital allodynia and increases in nociceptive neuropeptides in the brainstem in a mouse model of controlled cortical impact (CCI) injury. METHODS: Male C57BL/6 mice received either CCI or craniotomy-only followed by weekly periorbital von Frey (mechanical) sensory testing for up to 28 days post-injury. Mice receiving an incision only and naïve mice were included as control groups. Changes in calcitonin gene-related peptide (CGRP) and substance P (SP) within the brainstem were determined using enzyme-linked immunosorbent assay and immunohistochemistry, respectively. Activation of ionized calcium-binding adaptor molecule-1-labeled macrophages/microglia and glial fibrillary acidic protein (GFAP)-positive astrocytes were evaluated using immunohistochemistry because of their potential involvement in nociceptor sensitization. RESULTS: Incision-only control mice showed no changes from baseline periorbital von Frey mechanical thresholds. CCI significantly reduced mean periorbital von Frey thresholds (periorbital allodynia) compared with baseline and craniotomy-only at each endpoint, analysis of variance P \u3c .0001. Craniotomy significantly reduced periorbital threshold at 14 days but not 7, 21, or 28 days compared with baseline threshold, P \u3c .01. CCI significantly increased SP immunoreactivity in the brainstem at 7 and 14 days but not 28 days compared with craniotomy-only and controls, P \u3c .001. CGRP levels in brainstem tissues were significantly increased in CCI groups compared with controls (incision-only and naïve mice) or craniotomy-only mice at each endpoint examined, P \u3c .0001. There was a significant correlation between CGRP and periorbital allodynia (P \u3c .0001, r = -0.65) but not for SP (r = 0.20). CCI significantly increased the number of macrophage/microglia in the injured cortex at each endpoint up to 28 days, although cell numbers declined over weeks post-injury, P \u3c .001. GFAP(+) immunoreactivity was significantly increased at 7 but not 14 or 28 days after CCI, P \u3c .001. Craniotomy resulted in transient periorbital allodynia accompanied by transient increases in SP, CGRP, and GFAP immunoreactivity compared with control mice. There was no increase in the number of macrophage/microglia cells compared with controls after craniotomy. CONCLUSION: Injury to the somatosensory cortex results in persistent periorbital allodynia and increases in brainstem nociceptive neuropeptides. Findings suggest that persistent allodynia and increased neuropeptides are maintained by mechanisms other than activation of macrophage/microglia or astrocyte in the injured somatosensory cortex

Salmonella Infection After Craniotomy.

Salmonella is an uncommon cause of meningitis, especially after neurosurgery. Here, we present a case of Salmonella meningitis after craniotomy, likely due to physical contact with a snake after surgery, with contiguous spread from the patient's hand to her wound. The purpose of this report is to serve as a reminder that patients undergoing neurosurgery should avoid contact with pets, including snakes and other reptiles, in the postoperative period and practice good hand hygiene

Acute management of poor condition subarachnoid hemorrhage patients

Poor condition subarachnoid hemorrhage (SAH) patients present a high mortality and morbidity. In this study, we reviewed the acute interventional (surgical and endovascular) management of 109 SAH-poor condition patients, who were treated as early as logistically possible after confirming stable circulation parameters. Patients over the age of 70 years, without clinical response to painful stimulation were excluded. We recognized at least 3 different postinterventional therapeutic approaches: (1) Norm- or hypovolemic, normotensive hemodilution in 30 patients with space-occupying intracranial hematomas as well as in 31 cases with acute cerebro-spinal-fluid obstruction. (2) Normovolemic, hypertensive hemodilution after unilateral decompressive craniotomy in 23 surgical- and 2 endovascular-treated patients with focalized space occupying lesions and reduced cerebral perfusion. (3) Hypovolemic, normo-, or hypertensive hemodilution after bilateral decompressive craniotomy in 23 cases with massive brain-swelling. We observed a reduced mortality (21%). The overall late outcome was favorable in 56% and unfavorable in 23%. Selective aggressive treatment adapted to increase the cerebral perfusion, seems to be an effective therapy to improve the survival and outcome of several poor condition SAH-patients

Comparison of Outcomes in Level I vs Level II Trauma Centers in Patients Undergoing Craniotomy or Craniectomy for Severe Traumatic Brain Injury.

BACKGROUND: Traumatic brain injury (TBI) carries a devastatingly high rate of morbidity and mortality. OBJECTIVE: To assess whether patients undergoing craniotomy/craniectomy for severe TBI fare better at level I than level II trauma centers in a mature trauma system. METHODS: The data were extracted from the Pennsylvania Trauma Outcome Study database. Inclusion criteria were patients \u3e 18 yr with severe TBI (Glasgow Coma Scale [GCS] score less than 9) undergoing craniotomy or craniectomy in the state of Pennsylvania from January 1, 2002 through September 30, 2017. RESULTS: Of 3980 patients, 2568 (64.5%) were treated at level I trauma centers and 1412 (35.5%) at level II centers. Baseline characteristics were similar between the 2 groups except for significantly worse GCS scores at admission in level I centers (P = .002). The rate of in-hospital mortality was 37.6% in level I centers vs 40.4% in level II centers (P = .08). Mean Functional Independence Measure (FIM) scores at discharge were significantly higher in level I (10.9 ± 5.5) than level II centers (9.8 ± 5.3; P \u3c .005). In multivariate analysis, treatment at level II trauma centers was significantly associated with in-hospital mortality (odds ratio, 1.2; 95% confidence interval, 1.03-1.37; P = .01) and worse FIM scores (odds ratio, 1.4; 95% confidence interval, 1.1-1.7; P = .001). Mean hospital and ICU length of stay were significantly longer in level I centers (P \u3c .005). CONCLUSION: This study showed superior functional outcomes and lower mortality rates in patients undergoing a neurosurgical procedure for severe TBI in level I trauma centers

Lifespan extension and the doctrine of double effect

Recent developments in biogerontology—the study of the biology of ageing—suggest that it may eventually be possible to intervene in the human ageing process. This, in turn, offers the prospect of significantly postponing the onset of age-related diseases. The biogerontological project, however, has met with strong resistance, especially by deontologists. They consider the act of intervening in the ageing process impermissible on the grounds that it would (most probably) bring about an extended maximum lifespan—a state of affairs that they deem intrinsically bad. In a bid to convince their deontological opponents of the permissibility of this act, proponents of biogerontology invoke an argument which is grounded in the doctrine of double effect. Surprisingly, their argument, which we refer to as the ‘double effect argument’, has gone unnoticed. This article exposes and critically evaluates this ‘double effect argument’. To this end, we first review a series of excerpts from the ethical debate on biogerontology in order to substantiate the presence of double effect reasoning. Next, we attempt to determine the role that the ‘double effect argument’ is meant to fulfil within this debate. Finally, we assess whether the act of intervening in ageing actually can be justified using double effect reasoning

Medical Malpractice of Vestibular Schwannoma: A 40-Year Review of the United States Legal Databases.

OBJECTIVES:To analyze medical malpractice lawsuit trends pertaining to cases of vestibular schwannomas (VS). METHODS:Two major computerized legal databases (LexisNexis and WestLaw) were queried and reviewed for evaluation of all the US state and federal court records from civil trials alleging malpractice between 1976 and 2016. RESULTS:A total of 32 VS cases were identified. Allegations were divided into four categories: misdiagnosis/delayed diagnosis (47%), postoperative complications (44%), failure of informed consent or information sharing (16%), and other (3%). Postoperative complications included facial nerve paralysis, myocardial infarction, meningitis, and intracranial hemorrhage. Judgment amounts ranged from $300,000 to$2,000,000. The specialist type was specified for 24 of the 32 cases (75%): neurosurgeons (n = 9; 37%), neurotologists (n = 6; 25%), general otolaryngologists (n = 5; 21%), primary care physicians (n = 4; 17%), neurologists (n = 3; 12%), radiologists (n = 3; 12%), anesthesiologists (n = 2; 8%), radiation oncologists (n = 1; 4%), and general surgeon (n = 1; 4%). Of these 24 cases, (n = 9; 37%) two or more physicians were named as defendants in the lawsuit. CONCLUSIONS:Enhanced physician-patient communication, ensuring proper and adequate patient consent procedures, and proper documentation are good practices that may decrease the likelihood of lawsuits

Continuous volumetric imaging via an optical phase-locked ultrasound lens

In vivo imaging at high spatiotemporal resolution is key to the understanding of complex biological systems. We integrated an optical phase-locked ultrasound lens into a two-photon fluorescence microscope and achieved microsecond-scale axial scanning, thus enabling volumetric imaging at tens of hertz. We applied this system to multicolor volumetric imaging of processes sensitive to motion artifacts, including calcium dynamics in behaving mouse brain and transient morphology changes and trafficking of immune cells

Symptomatic CNS Radiation Necrosis Requiring Neurosurgical Resection During Treatment with Lorlatinib in ALK-Rearranged NSCLC: A Report of Two Cases.

Central nervous system (CNS) metastasis carries a significant morbidity and mortality in anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC). Next-generation ALK tyrosine kinase inhibitors (TKIs) are highly CNS-penetrant and have demonstrated remarkable intracranial activity across clinical studies, and yet radiation remains the mainstay of treatment modality against CNS metastasis. We have previously reported alectinib can induce CNS radiation necrosis even after a remote history of radiation (7 years post-radiation). Lorlatinib is another potent next-generation ALK TKI that can overcome many ALK resistance mutations and has been shown to have excellent activity in patients with baseline CNS metastasis. Here we report two ALK-rearranged NSCLC patients who developed radiation necrosis shortly after initiating lorlatinib following progression on the sequential treatment of crizotinib, alectinib, and brigatinib. In both cases, radiation necrosis is evidenced by serial MRI images and histological examination of the resected CNS metastasis that had previously been radiated. Our cases highlight the importance of recognizing CNS radiation necrosis that may mimic disease progression in ALK-rearranged NSCLC treated with and potentially precipated by next-generation ALK TKIs