Pharmacogenetic activation of parvalbumin interneurons in the prefrontal cortex rescues cognitive deficits induced by adolescent MK801 administration.

The cognitive symptoms of schizophrenia (SZ) present a significant clinical burden. They are treatment resistant and are the primary predictor of functional outcomes. Although the neural mechanisms underlying these deficits remain unclear, pathological GABAergic signaling likely plays an essential role. Perturbations with parvalbumin (PV)-expressing fast-spiking (FS) interneurons in the prefrontal cortex (PFC) are consistently found in post-mortem studies of patients with SZ, as well as in animal models. Our studies have shown decreased prefrontal synaptic inhibition and PV immunostaining, along with working memory and cognitive flexibility deficits in the MK801 model. To test the hypothesized association between PV cell perturbations and impaired cognition in SZ, we activated prefrontal PV cells by using an excitatory DREADD viral vector with a PV promoter to rescue the cognitive deficits induced by adolescent MK801 administration in female rats. We found that targeted pharmacogenetic upregulation of prefrontal PV interneuron activity can restore E/I balance and improve cognition in the MK801 model. Our findings support the hypothesis that the reduced PV cell activity levels disrupt GABA transmission, resulting in the disinhibition of excitatory pyramidal cells. This disinhibition leads to an elevated prefrontal excitation/inhibition (E/I) balance that could be causal for cognitive impairments. Our study provides novel insights into the causal role of PV cells in cognitive function and has clinical implications for understanding the pathophysiology and management of SZ.

Mycotic aneurysm presenting as subdural empyema: illustrative case.

BACKGROUND: Mycotic aneurysms (MAs) are rare intracranial pathologies. They are associated with spontaneous rupture, which is often the first presenting sign. Subarachnoid hemorrhage and intraparenchymal hemorrhage are the most common sequelae of ruptured MAs, with subdural hematoma being an atypical presentation. The presentation of an MA as a subdural empyema has not yet been reported in the literature. OBSERVATIONS: The authors discussed a 68-year-old man who presented with subdural empyema and received surgery for evacuation. He was found to have a ruptured mycotic aneurysm intraoperatively. LESSONS: This case demonstrated a rare and atypical presentation of an MA.

Bilateral pallidal DBS for blepharospasm: A case report and review of the literature.

Background: Deep brain stimulation (DBS) of the globus pallidus internus (GPi) in the treatment of craniocervical dystonia often requires an extended period of stimulation parameter manipulations. Case Description: We present a patient suffering from debilitating blepharospasm treated with bilateral DBS of the GPi alongside 7 years of stimulation parameter manipulations and a literature review of comparable patients. Conclusion: Our literature review suggests that a patient's specific dystonic symptoms can guide stimulation parameter manipulations. Further research regarding trends in stimulation parameters being used in the field for different dystonic symptoms may expedite the stimulation parameter manipulation process.

It's not always the shunt: Microthombi formation in venous collaterals causing symptoms of shunt failure in the setting of shunted hydrocephalus.

We present a patient with a history of shunted hydrocephalus due to neonatal iatrogenic thoracic venous occlusion with subsequent interval development of spontaneous thoracic venous collateral occlusion as a young adult presenting with symptoms of ventriculoperitoneal shunt failure. Though the patient's presenting symptoms were suggestive of shunt failure in the setting of known shunt dependent hydrocephalus, specific ophthalmologic findings, including venous engorgement, retinal and subconjunctival hemorrhages as well as periorbital edema in conjunction with papilledema, led to the correct diagnosis of cranio-orbital congestion secondary to microthrombi formation in the venous collateral anomalies of her chest wall. This pathology was successfully managed with warfarin.

Acute myeloid leukemia presenting as horizontal diplopia.

Acute myeloid leukemia (AML) accounts for 16% of all leukemias in children. Prognosis in the pediatric population is better than that of older populations, with a younger age at diagnosis being a favorable prognostic factor [1]. Diplopia is a rare first presenting sign of AML. We present a 15 year old male complaining of diplopia and unilateral orbital swelling. Workup in the emergency department found normal neuroimaging but revealed a markedly elevated leukocytosis with anemia and thrombocytopenia. Peripheral smear showed increased blast cells >10%. This patient was ultimately diagnosed with AML. This case demonstrates an atypical presentation of AML and urges a thorough work up for patients presenting with unexplained diplopia.

The DOWN Questionnaire: A Novel Screening Tool for Cervical Spondylotic Myelopathy.

STUDY DESIGN: Case-control study. OBJECTIVES: Cervical spondylotic myelopathy (CSM) is the most common cause of spinal cord injury in adults aged over 55 years. However, since the onset is typically insidious, accurately diagnosing CSM can be challenging, often requiring referral to a subspecialist and advanced imaging. To help identify patients at risk for CSM, this case-control study compared responses to a series of 4 questions (DOWN questionnaire) in myelopathic and non-myelopathic patients. METHODS: Ninety-two patients, 46 with and 46 without myelopathy, were recruited for the study. Each patient answered 4 questions encompassing common symptoms associated with CSM. Responses between patient groups were compared, and Cohen's κ was used to assess for agreement between responses and the diagnosis of myelopathy. RESULTS: We found a sensitivity of 91% and a κ of 0.54 to 3 positive responses and a sensitivity of 72% and a κ of 0.61 to 4 positive responses. CONCLUSIONS: Positive responses to 3 or more DOWN questions has high sensitivity and moderate agreement with the diagnosis of myelopathy based on history, physical exam, and review of advanced imaging by an orthopedic or neurological surgeon. The DOWN questionnaire is a potentially useful screening tool to identify patients at risk for CSM.

Prospective clinical validation of a meningioma consistency grading scheme: association with surgical outcomes and extent of tumor resection.

OBJECTIVEThe present study aims to assess the clinical utility of a previously validated intraoperative meningioma consistency grading scale and its association with extent of resection (EOR) and various surgical outcomes.METHODSThe previously validated grading system was prospectively assessed in 127 consecutive patients undergoing open craniotomy for meningioma by multiple neurosurgeons at two high-volume academic hospitals from 2013 to 2016. Consistency grading scores ranging from 1 (soft) to 5 (firm/calcified) were retrospectively analyzed to test for association with surgical outcomes and EOR, categorized as gross-total resection (GTR) or subtotal resection, defined by postoperative MRI.RESULTSOne hundred twenty-seven patients were included in the analysis with a tumor consistency distribution as follows: grade 1, 3.1%; grade 2, 14.2%; grade 3, 44.1%; grade 4, 32.3%; and grade 5, 6.3%. The mean tumor diameter was 3.6 ± 1.7 cm. Tumor consistency grades were grouped into soft (grades 1 and 2), average (grade 3), and firm (grades 4 and 5) groups for statistical analysis with distributions of 17.3%, 44.1%, and 38.6%, respectively. There was no association between meningioma consistency and maximal tumor diameter, or location. Mean duration of surgery was longer for tumors with higher consistency: grades 1 and 2, 186 minutes; grade 3, 219 minutes; and grades 4 and 5, 299 minutes (p = 0.000028). There was a trend toward higher perioperative complication rates for tumors of increased consistency: grades 1 and 2, 4.5%; grade 3, 7.0%; and grades 4 and 5, 20.8% (p = 0.047). The proportion of GTR for each consistency group was as follows: grades 1 and 2, 77%; grade 3, 68%; and grades 4 and 5, 43% (p = 0.0062).CONCLUSIONSIn addition to other important meningioma characteristics such as invasiveness, tumor consistency is a key determinant of surgical outcomes, including operative duration and EOR. Future studies predicting tumor consistency based on preoperative neuroimaging will help considerably with preoperative planning for meningiomas.

Paraplegic patients: how to measure balance and what is normal or functional?

PURPOSE: To review the current understanding and data of sagittal balance and alignment considerations in paraplegic patients. METHODS: A PubMed literature search was conducted to identify all relevant articles relating to sagittal alignment and sagittal balance considerations in paraplegic and spinal cord injury patients. RESULTS: While there are numerous studies and publications on sagittal balance in the ambulatory patient with spinal deformity or complex spine disorders, there is paucity of the literature on "normal" sagittal balance in the paraplegic patients. Studies have reported significantly alterations of the sagittal alignment parameters in the non-ambulatory paraplegic patients compared to ambulatory patients. The variability of the alignment changes is related to the differences in the level of the spinal cord injury and their differences in the activations of truncal muscles to allow functional movements in those patients, particularly in optimizing sitting and transferring. Surgical goal in treating paraplegic patients with complex pathologies should not be solely directed to achieve the "normal" radiographic parameters of sagittal alignment in the ambulatory patients. The goal should be to maintain good coronal balance to allow ideal sitting position and to preserve motion segment to optimize functions of paraplegia patients. CONCLUSION: Current available literature data have not defined normal sagittal parameters for paraplegic patients. There are significant differences in postural sagittal parameters and muscle activations in paraplegic and non-spinal cord injury patients that can lead to differences in sagittal alignment and balance. Treatment goal in spine surgery for paraplegic patients should address their global function, sitting balance, and ability to perform self-care rather than the accepted radiographic parameters for adult spinal deformity in ambulatory patients.

Identification and repair of intraoperative cerebrospinal fluid leaks in endonasal transsphenoidal pituitary surgery: surgical experience in a series of 1002 patients.

OBJECTIVE Cerebrospinal fluid (CSF) rhinorrhea is among the most common complications following transsphenoidal surgery for sellar region lesions. The aim of this study was to review the authors' institutional experience in identifying, repairing, and treating CSF leaks associated with direct endonasal transsphenoidal operations. METHODS The authors performed a retrospective review of cases involving surgical treatment of pituitary adenomas and other sellar lesions at the University of Southern California between December 1995 and March 2016. Inclusion criteria included all pathology of the sellar region approached via a direct microscopic or endoscopic endonasal transsphenoidal approach. Demographics, pathology, intraoperative and postoperative CSF leak rates, and other complications were recorded and analyzed. A literature review of the incidence of CSF leaks associated with the direct endonasal transsphenoidal approach to pituitary lesions was conducted. RESULTS A total of 1002 patients met the inclusion criteria and their cases were subsequently analyzed. Preoperative diagnoses included pituitary adenomas in 855 cases (85.4%), Rathke's cleft cyst in 94 (9.4%), and other sellar lesions in 53 (5.2%). Lesions with a diameter ≥ 1 cm made up 49% of the series. Intraoperative repair of an identified CSF leak was performed in 375 cases (37.4%) using autologous fat, fascia, or both. An additional 92 patients (9.2%) underwent empirical sellar reconstruction without evidence of an intraoperative CSF leak. Postoperative CSF leaks developed in 26 patients (2.6%), including 13 (1.3% of the overall group) in whom no intraoperative leak was identified. Among the 26 patients who developed a postoperative CSF leak, 13 were noted to have intraoperative leak and underwent sellar repair while the remaining 13 did not have an intraoperative leak or sellar repair. No patients who underwent empirical sellar repair without an intraoperative leak developed a postoperative leak. Eight patients underwent additional surgery (0.8% reoperation rate) for CSF leak repair, and 18 were successfully treated with lumbar drainage or lumbar puncture alone. The incidence of postoperative CSF rhinorrhea in this series was compared with that in 11 other reported series that met inclusion criteria, with incidence rates ranging between 0.6% and 12.1%. CONCLUSIONS In this large series, half of the patients who developed postoperative CSF rhinorrhea had no evidence of intraoperative CSF leakage. Unidentified intraoperative CSF leaks and/or delayed development of CSF fistulas are equally important sources of postoperative CSF rhinorrhea as the lack of employing effective CSF leak repair methods. Empirical sellar reconstruction in the absence of an intraoperative CSF leak may be of benefit following resection of large tumors, especially if the arachnoid is thinned out and herniates into the sella.

Endoscopic-Assisted Median Aperture Approach for Resection of Fourth Ventricular Tumor and Confirmation of Patency of Cerebral Aqueduct Using an Adjustable-Angle Endoscope: Technical Case Report.

BACKGROUND AND IMPORTANCE: Open microsurgical approaches to the roof of the fourth ventricle via a telovelar approach typically require cerebellar retraction and/or splitting of the vermis and may be associated with postoperative neurological morbidities. In this case report and technical note, we describe the use of an adjustable-angle endoscope inserted into the median aperture via suboccipital craniotomy, resulting in enhanced visualization of the roof of the fourth ventricle and cerebral aqueduct and maximal safe tumor resection. CLINICAL PRESENTATION: A 49-yr-old woman with obstructive hydrocephalus and a fourth ventricular mass that was not fully visible with the use of an operative microscope. CONCLUSION: Direct visualization of the roof of the fourth ventricle, including the superior medullary velum and cerebral aqueduct, can be facilitated with an adjustable angle endoscope inserted into the median aperture via suboccipital craniotomy to minimize the degree of telovelar dissection and vermis splitting.

Effect of mental health on post-operative infection rates following cervical spine fusion procedures.

PURPOSE: The aim of this study was to determine whether having an existing psychiatric disorder is a risk factor for developing post-operative infection following anterior cervical discectomy with fusion (ACDF) and posterior cervical fusion (PCF). RESULTS: A total of 34,007 patients within Humana database was included in this study. Patients with mental disorders had post-operative infection rates of 3.2% and 4.4% within 1 and 3months, compared to 2.5% and 3.5% in patients without a psychiatric disorder (p < 0.05). CONCLUSIONS: Patients with mental disorders had significantly higher rates of post-operative infection compared to patients who were never diagnosed with a psychiatric disorder.

Space Available for Cord, Motion, and disc degeneration at the adjacent segments level of degenerative cervical spondylolisthesis using kinematic MRI.

The objective was to evaluate motion, disc degeneration and Space Available for Cord (SAC) at the adjacent segments of degenerative cervical spondylolisthesis (DCS) using kinematic Magnetic Resonance Imaging (kMRI). The cervical spine kMRI of sixty-one DCS spinal levels (38 anterolisthesis and 23 retrolisthesis) were analyzed at the listhesis level and its adjacent segments in three position using kMRI. MRAnalyzer3 was used to analyze translation, angular motion and SAC. The caudad level had significantly less translation motion than the listhesis level in overall DCS or grade 2 anterolisthesis group (P<0.05). The cephalad level had significant more translational motion than the caudad level in overall DCS or grade 1 retrolisthesis group (P<0.05). For disc degeneration, the cephalad level had the least disc degeneration and showed significant difference with the listhesis level in overall DCS or overall anterolisthesis or overall retrolisthesis or grade 2 anterolisthesis or grade 1 or 2 retrolisthesis (P<0.05). For SAC, the listhesis level had the narrowest space in overall DCS groups. In neutral position, grade 1 anterolisthesis had significantly larger SAC at the listhesis and the cephalad level than grade 1 retrolisthesis (P<0.05). In conclusion, DCS affected cervical spine motion and kinematics. Grade 1 retrolisthesis showed tendency of narrower SAC at the cephalad level more than the same grade anterolisthesis. The likelihood of the adjacent segment disease and spinal cord compression are higher in both grade 2 anterolisthesis and retrolisthesis.

Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines on the Management of Patients With Nonfunctioning Pituitary Adenomas: Executive Summary.

BACKGROUND: Nonfunctioning pituitary adenomas (NFPAs) are the most frequent pituitary tumors. OBJECTIVE: To create evidence-based guidelines for the initial management of NFPAs. METHODS: A multidisciplinary task force composed of physician volunteers and evidence-based medicine-trained methodologists conducted a systematic review of the literature relevant to the management of NFPAs. To ascertain the class of evidence for the posttreatment follow-ups, the task force used the Clinical Assessment evidence-based classification. RESULTS: Seven topics of importance were chosen for detailed evaluation. The topics addressed include preoperative evaluation, primary treatment, treatment options for residual tumors after surgery, and postoperative patient management. For preoperative patient evaluation, the guideline task force focused on preoperative imaging, preoperative laboratory evaluation, and preoperative ophthalmologic evaluation. For primary treatment, this guideline addresses surgical resection, medical therapy, radiation therapy, the natural history of untreated tumors, surgical methodologies, such as endoscopy, microscopy, or craniotomy, and intraoperative adjuncts like neuronavigation, cerebrospinal fluid diversion, or intraoperative imaging. For residual tumor treatment, the guideline task force evaluated radiation vs observation. Additional topics addressed in this guideline regarding postoperative patient management include the frequency of postoperative imaging, postoperative endocrine evaluation, and postoperative ophthalmologic evaluation. CONCLUSION: Although there is clearly a need for more randomized trials generating higher levels of evidence to help guide physicians managing NFPAs, the existing evidence provided valuable data upon which the guidelines described in the 7 articles generated from this effort are based. The full guidelines document can be located at https://www.cns.org/guidelines/guidelines-management-patients-non-functioning-pituitary-adenomas. ABBREVIATION: NFPA, nonfunctioning pituitary adenoma.

Congress of Neurological Surgeons Systematic Review and Evidence-Based Guideline on Primary Management of Patients With Nonfunctioning Pituitary Adenomas.

BACKGROUND: Nonfunctioning pituitary adenomas (NFPAs) are among the most common pituitary lesions and may present clinically with vision loss and hypopituitarism. OBJECTIVE: To characterize the existing literature as it pertains to the initial management of NFPAs. METHODS: A systematic literature review was conducted to identify and screen articles assessing primary treatment options (surgical, medical, radiation based, or observation) for NFPAs. Outcomes assessed included vision-, endocrine-, and headache-related symptoms, as well as tumor response to therapy. Twenty-five studies met inclusion criteria for analysis. RESULTS: A considerable amount of class II evidence (14 studies) was identified supporting primary surgical intervention in patients with symptomatic NFPA macroadenomas, resulting in immediate tumor volume reduction in nearly all patients and a residual tumor rate of 10% to 36%. One prospective, observational cohort study and multiple retrospective studies showed improved visual function in 75% to 91% of surgically treated patients and improved hypopituitarism in 35% to 50% of patients. Limited class II evidence showed inconsistent benefits for observation alone (1 study), primary radiation-based treatment (3 studies), or primary medical treatment (8 studies) for improving vision, headaches, hypopituitarism, or tumor volume. One retrospective study implementing observation alone showed tumor progression in 50% of patients and a requirement for surgery in 21% of patients. Eight studies assessing primary medical therapy for NFPAs showed inconsistent tumor response rates using somatostatin analogs (12%-40% response rate), dopamine agonist therapy (0%-61% response rate), or combination therapy (60% response rate). Three studies reporting primary radiosurgery for NFPAs showed decreased tumor size in 38% to 60% of patients. CONCLUSION: Multiple retrospective and some prospective studies have demonstrated consistent effectiveness of primary surgical resection of symptomatic NFPAs with acceptable morbidity rates. Limited and inconsistent reports are available for alternative treatment strategies, including radiation, medical treatment, and observation alone; these modalities may, however, play a valid role in patients who are not surgical candidates. Based on the available evidence, the authors recommend surgical resection as the preferred primary intervention for symptomatic NFPAs. The full guidelines document for this chapter can be located at https://www.cns.org/guidelines/guidelines-management-patients-non-functioning-pituitary-adenomas/Chapter_5. ABBREVIATION: NFPA, nonfunctioning pituitary adenoma.

Endoscopic Endonasal and Keyhole Surgery for the Management of Skull Base Meningiomas.

The resection of anterior skull base meningiomas has traditionally been performed via pterional or unilateral/bilateral subfrontal craniotomies. The supraorbital keyhole approach and the endoscopic endonasal approach, techniques in which the endoscope is used to aid visualization, were developed to provide alternative, less-invasive approaches to aid the resection of these tumors. The individual characteristics of each tumor, such as location and size, are the main determinants guiding the choice of approach. In this article, the advantages and disadvantages of each approach are discussed, along with complications specific to each technique. Furthermore, a detailed procedural description of each surgical approach is described.

Ectopic ACTH-secreting pituitary adenoma of the sphenoid sinus: case report of endoscopic endonasal resection and systematic review of the literature.

Ectopic pituitary adenomas are exceedingly rare entities that are often misdiagnosed. The resulting delay in diagnosis may be particularly concerning in the case of Cushing syndrome caused by an ectopic adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma. Although the total resection of ectopic adenomas results in rapid and durable remission, persistent Cushing syndrome is often associated with permanently damaging invasive procedures and significantly higher risk of mortality. The authors report the case of a 48-year-old man with ACTH-dependent Cushing syndrome. On the morning before surgery, his serum cortisol measured 51 µg/dl, his ACTH level was 195.7 pg/ml, and his urinary free cortisol level was 2109 µg/day. Serum cortisol was not suppressed with the administration of high-dose dexamethasone. Imaging showed separate masses in both the sphenoid sinus and the pituitary gland, complicating the diagnostic process and requiring pathological assessment of both masses. No other abnormalities were found on thoracic, abdominal, or pelvic scans. Gross-total resection of both lesions was accomplished via an endoscopic endonasal transsphenoidal approach. Pathology confirmed an ectopic ACTH pituitary adenoma of the sphenoid sinus and a Crooke hyaline change of the pituitary gland. The patient achieved stable hormonal remission without significant postoperative complications, returned to full activity within 3 months, and remained disease free nearly 1 year after tumor resection. In a systematic literature review, the authors identified 41 cases of ectopic ACTH-secreting pituitary adenomas, including 18 arising in the sphenoid sinus without direct involvement of the sella. Including the case described here, the total number of ectopic ACTH pituitary adenomas arising in the sphenoid sinus was 19, and the total number of ectopic ACTH pituitary adenomas without regard to location was 42. For the 19 patients with adenomas found in the sphenoid sinus, ages ranged from 16 to 76 years, and there were 15 women and 4 men. The mean and median diameters of the resected sphenoid masses were 13.9 and 8 mm, respectively, with a range of 3-55 mm. Seven were microadenomas (< 1 cm). Fifteen of the 19 cases reported serum ACTH and morning cortisol levels, the means of which were 106.7 pg/ml and 32.5 µg/dl, respectively. Gross-total tumor resection was achieved in all patients except one, and in all of them durable hormonal remission of Cushing syndrome was achieved (mean follow-up time 20 months). Ectopic pituitary adenomas are rare but important causes of Cushing syndrome and related endocrinopathies, particularly because of the rapid onset and severity of symptoms with atypical presentation. Ectopic pituitary adenomas, especially those in the nasal cavity, nasopharynx, or paranasal sinuses, are easily misidentified. Any patient presenting with signs and symptoms of Cushing syndrome without any obvious pituitary adenoma or other sources of hypercortisolemia should be thoroughly screened for an ectopic adenoma. However, as with the case presented here, the coincident existence of a sellar mass should not preclude the possibility of an ectopic source. There should be a high degree of clinical suspicion for any mass in the general area surrounding the sella when evaluating Cushing syndrome.

Endoscopic extended transsphenoidal resection of craniopharyngiomas: nuances of neurosurgical technique.

Endoscopic approaches to the midline ventral skull base have been extensively developed and refined for resection of cranial base tumors over the past several years. As these techniques have improved, both the degree of resection and complication rates have proven comparable to those for transcranial approaches, while visual outcomes may be better via endoscopic endonasal surgery and hospital stays and recovery times are often shorter. Yet for all of the progress made, the steep learning curve associated with these techniques has hampered more widespread implementation and adoption. The authors address this obstacle by coupling a thorough description of the technical nuances for endoscopic endonasal craniopharyngioma resection with detailed illustrations of the important steps in the operation. Traditionally, transsphendoidal approaches to craniopharyngiomas have been restricted to lesions mostly confined to the sella. However, recently, endoscopic endonasal resections are more frequently employed for extrasellar and purely third ventricle craniopharyngiomas, whose typical retrochiasmatic location makes them ideal candidates for endoscopic transnasal surgery. The endonasal endoscopic approach offers many advantages, including direct access to the long axis of the tumor, early tumor debulking with minimal manipulation of the optic apparatus, more precise visualization of tumor planes, particularly along the undersurface of the chiasm and the roof of the third ventricle, and a minimal-access corridor that obviates the need for brain retraction. Although much emphasis has been placed on technical tenets of exposure and "how to get there," this article focuses on nuances of tumor resection "when you are there." Three operative videos illustrate our discussion of technical tenets.