Eyebrow supraorbital keyhole craniotomy for olfactory groove meningiomas with endoscope assistance: case series and systematic review of extent of resection, quantification of postoperative frontal lobe injury, anosmia, and recurrence.

BACKGROUND: Olfactory groove meningiomas (OGMs) are commonly treated with open craniotomy. Endonasal approaches have also been described. OBJECTIVE: To present clinical and radiographic outcomes for the minimally invasive eyebrow incision supraorbital keyhole approach with endoscopic assistance for OGMs. METHODS: We performed a retrospective single-center cohort study and a systematic literature review. RESULTS: Fifteen patients were identified, all with Grade I meningiomas. Radiographic gross total resection of enhancing tumor was achieved in all patients. Mean frontal lobe fluid-attenuated inversion recovery volume decreased from 11.1 ± 18.3 cm3 preoperatively to 9.9 ± 11.4 cm3 immediately postoperatively, and there was minimal new restricted diffusion (3.2 ± 2.2 cm3; max 7.5 cm3). Median length of stay was 3 days (range 2-8). Vision was improved in 4 (80%) and stable in 1 (20%) of 5 patients with a preoperative deficit. New postoperative anosmia occurred in 3 (23%) of 13 patients with any preoperative olfaction. All patients were satisfied with their cosmetic result at 3 months. After a median follow-up of 32.2 months, there were 2 (13.3%) asymptomatic radiographic recurrences, 1 treated with radiosurgery and the other with endoscopic endonasal approach (EEA). No patients required further craniotomy. Systematic review revealed the present series to be the largest to date reporting disaggregated outcomes for the eyebrow approach to OGM. CONCLUSION: The eyebrow incision supraorbital keyhole craniotomy with endoscopic assistance is a safe and effective approach to OGM with tumor control rates similar to more invasive open approaches and better than the endonasal approach. Rates of frontal lobe injury, CSF leak and anosmia are comparatively low.

Endonasal endoscopic transsphenoidal resection of intrinsic third ventricular craniopharyngioma: surgical results.

OBJECTIVEIntrinsic third ventricular craniopharyngiomas (IVCs) have been reported by some authors to "pose the greatest surgical challenge" of all craniopharyngiomas (CPAs). A variety of open microsurgical approaches have historically been used for resection of these tumors. Despite increased utilization of the endoscopic endonasal approach (EEA) for resection of CPAs in recent years, many authors continue to recommend against use of the EEA for resection of IVCs. In this paper, the authors present the largest series to date utilizing the EEA to remove IVCs.METHODSThe authors reviewed a prospectively acquired database of the EEA for resection of IVCs over 14 years at Weill Cornell Medical College, NewYork-Presbyterian Hospital. Preoperative MR images were examined independently by two neurosurgeons and a neuroradiologist to identify IVCs. Pre- and postoperative endocrinological, ophthalmological, radiographic, and other morbidities were determined from retrospective chart review and volumetric radiographic analysis.RESULTSBetween January 2006 and August 2017, 10 patients (4 men, 6 women) ranging in age from 26 to 67 years old, underwent resection of an IVC utilizing the EEA. Preoperative endocrinopathy was present in 70% and visual deterioration in 60%. Gross-total resection (GTR) was achieved in 9 (90%) of 10 patients, with achievement of near-total (98%) resection in the remaining patient. Pathology was papillary in 30%. Closure incorporated a "gasket-seal" technique with nasoseptal flap coverage and either lumbar drainage (9 patients) or a ventricular drain (1 patient). Postoperatively, complete anterior and posterior pituitary insufficiency was present in 90% and 70% of patients, respectively. In 4 patients with normal vision prior to surgery, 3 had stable vision following tumor resection. One patient noted a new, incongruous, left inferior homonymous quadrantanopsia postoperatively. In the 6 patients who presented with compromised vision, 2 reported stable vision following surgery. Each of the remaining 4 patients noted significant improvement in vision after tumor resection, with complete restoration of normal vision in 1 patient. Aside from the single case (10%) of visual deterioration referenced above, there were no instances of postoperative neurological decline. Postoperative CSF leakage occurred in 1 morbidly obese patient who required reoperation for revision of closure. After a mean follow-up of 46.8 months (range 4-131 months), tumor recurrence was observed in 2 patients (20%), one of whom was treated with radiation and the other with chemotherapy. Both of these patients had previously undergone GTR of the IVC.CONCLUSIONSThe 10 patients described in this report represent the largest number of patients with IVC treated using EEA for resection to date. EEA for resection of IVC is a safe and efficacious operative strategy that should be considered a surgical option in the treatment of this challenging subset of tumors.

Stereotactic laser induced thermotherapy (LITT): a novel treatment for brain lesions regrowing after radiosurgery.

Since the inception of radiosurgery, the management of brain metastases has become a common problem for neurosurgeons. Although the use of stereotactic radiosurgery and/or whole brain radiation therapy serves to control the majority of disease burden, patients who survive longer than 6-8 months sometimes face the problem of symptomatic radiographically regrowing lesions with few treatment options. Here we investigate the feasibility of use of MRI-guided stereotactic laser induced thermotherapy (LITT) as a novel treatment option for these lesions. Six patients who had previously undergone gamma knife stereotactic radiosurgery for brain metastases were selected. All patients had an initial favorable response to radiosurgery but subsequently developed regrowth of at least one lesion associated with recurrent edema and progressive neurological symptoms requiring ongoing steroids for symptom control. All lesions were evaluated for craniotomy, but were deemed unresectable due to deep location or patient's comorbidities. Stereotactic biopsies were performed prior to the thermotherapy procedure in all cases. LITT was performed using the Visualase system and follow-up MRI imaging was used to determine treatment response. In all six patients biopsy results were negative for tumor and consistent with adverse radiation effects also known as radiation necrosis. Patients tolerated the procedure well and were discharged from the hospital within 48 h of the procedure. In 4/6 cases there was durable improvement of neurological symptoms until death. In all cases steroids were weaned off within 2 months. One patient died from systemic causes related to his cancer a month after the procedure. One patient had regrowth of the lesion 3 months after the procedure and required re-initiation of steroids and standard craniotomy for surgical resection. There were no complications directly related to the thermocoagulation procedure. Stereotactic laser induced thermotherapy is a feasible alternative for the treatment of symptomatic regrowing metastatic lesions after radiosurgery. The procedure carries minimal morbidity and, in this small series, shows some effectiveness in the symptomatic relief of edema and neurological symptoms paralleled by radiographic lesional control. Further studies are necessary to elucidate the safety of this technology.

Proenkephalin mediates the enduring effects of adolescent cannabis exposure associated with adult opiate vulnerability.

BACKGROUND: Marijuana use by teenagers often predates the use of harder drugs, but the neurobiological underpinnings of such vulnerability are unknown. Animal studies suggest enhanced heroin self-administration (SA) and dysregulation of the endogenous opioid system in the nucleus accumbens shell (NAcsh) of adults following adolescent Δ(9)-tetrahydrocannabinol (THC) exposure. However, a causal link between proenkephalin (Penk) expression and vulnerability to heroin has yet to be established. METHODS: To investigate the functional significance of NAcsh Penk tone, selective viral-mediated knockdown and overexpression of Penk was performed, followed by analysis of subsequent heroin SA behavior. To determine whether adolescent THC exposure was associated with chromatin alteration, we analyzed levels of histone H3 methylation in the NAcsh via chromatin immunoprecipitation at five sites flanking the Penk gene transcription start site. RESULTS: Here we show that regulation of the Penk opioid neuropeptide gene in NAcsh directly regulates heroin SA behavior. Selective viral-mediated knockdown of Penk in striatopallidal neurons attenuates heroin SA in adolescent THC-exposed rats, whereas Penk overexpression potentiates heroin SA in THC-naïve rats. Furthermore, we report that adolescent THC exposure mediates Penk upregulation through reduction of histone H3 lysine 9 (H3K9) methylation in the NAcsh, thereby disrupting the normal developmental pattern of H3K9 methylation. CONCLUSIONS: These data establish a direct association between THC-induced NAcsh Penk upregulation and heroin SA and indicate that epigenetic dysregulation of Penk underlies the long-term effects of THC.

The kappa-opioid agonist U69,593 blocks cocaine-induced enhancement of brain stimulation reward.

BACKGROUND: Increasing evidence indicates that brain kappa-opioid receptors (KORs) are involved in regulation of mood states. In animal models often used to study psychiatric illness, KOR agonists produce depressive-like effects (e.g., anhedonia), whereas KOR antagonists produce antidepressant- and anxiolytic-like effects. The ability of KOR agonists to produce anhedonia-like signs in laboratory animals raises the possibility that this class of drugs might be useful to ameliorate states characterized by excess reward or motivation, such as mania or stimulant intoxication. METHODS: We examined how the selective KOR agonist U69,593 affects cocaine-induced facilitation of intracranial self-stimulation (ICSS), a model of the abnormally increased reward function that characterizes mania and stimulant intoxication. Rats with stimulating electrodes implanted in the medial forebrain bundle (MFB) were tested with intraperitoneal injections of U69,593 (.063-.5 mg/kg) alone, cocaine (1.25-10 mg/kg) alone, and combinations of the drugs. RESULTS: Cocaine dose-dependently decreased ICSS thresholds, indicating that it enhanced the rewarding impact of MFB stimulation. In contrast, U69,593 dose-dependently increased ICSS thresholds, indicating that it decreased the rewarding impact of the stimulation. Pretreatment with U69,593 blocked cocaine-induced decreases in ICSS thresholds at doses that had negligible effects on their own. CONCLUSIONS: Activation of KORs reduces the reward-related effects of cocaine. Inasmuch as cocaine-induced behavioral stimulation in rodents may model key aspects of enhanced mood in humans, these findings raise the possibility that KOR agonists might ameliorate symptoms of conditions characterized by increased motivation and hyperfunction of brain reward systems, such as mania and stimulant intoxication.

Sensitivity of the five-choice serial reaction time task to the effects of various psychotropic drugs in Sprague-Dawley rats.

BACKGROUND: Attentional deficits accompany many psychiatric disorders, underscoring the need for rodent models of attention to screen novel therapeutic agents and characterize the biological basis of attention. The five-choice serial reaction time task (5CSRTT) is one such model. Here, we characterized the effects of four standard psychotropic agents on performance in the 5CSRTT. METHODS: Male Sprague-Dawley rats were trained in the 5CSRTT (5-sec inter-trial interval and .5-sec stimulus duration) until they reliably performed at > 60% accuracy and < 20% omissions. They were then treated systemically with the stimulant methylphenidate (MPH) (.063-2.0 mg/kg), the N-methyl-D-aspartate antagonist dizocilpine (MK-801) (.008-.25 mg/kg), the norepinephrine reuptake inhibitor desipramine (DMI) (.63-10 mg/kg), or the kappa-receptor agonist U69,593 (.25-2.0 mg/kg) 30 min before testing. RESULTS: Methylphenidate (.5 mg/kg) increased accuracy. Dizocilpine impaired accuracy (.25 mg/kg), increased premature responses (.063-.25 mg/kg), and increased omissions (.25 mg/kg). Desipramine decreased premature responses (5.0 mg/kg) but increased omissions (10 mg/kg), correct response latencies (5.0-10.0 mg/kg), and reward latencies (5.0-10.0 mg/kg). The kappa-opioid agonist U69,593 (1.0-2.0 mg/kg) increased omissions and correct response latencies. CONCLUSIONS: In Sprague-Dawley rats, psychotropic drugs with distinct pharmacological profiles produced distinguishable effects in the 5CSRTT. The effects of these classes of drugs under our testing conditions are qualitatively similar to their effects in humans.

Behavioral effects of short-term administration of lithium and valproic acid in rats.

Lithium and valproic acid are mood-stabilizing agents that are often used to manage the episodes of mania and depression that characterize bipolar disorder. These agents develop clinical efficacy with chronic treatment, but the neurobiological actions that contribute to their therapeutic effects remain unclear. The present work was designed to study and compare various behavioral effects of short-term administration of lithium chloride (LiCl) and valproic acid (VPA) in rats. Specifically, we examined the effects of acute and sub-acute injections of these agents on locomotor activity, behavior in the forced swim test (FST), and intracranial self-stimulation (ICSS) thresholds. Locomotor activity studies were used to identify the range of doses with gross behavioral effects in rats. At doses below those that suppressed activity (total distance traveled, in cm) in 1-h test sessions, LiCl had prodepressant-like effects: it increased immobility in the FST, an effect opposite to that typically seen with standard antidepressants, and it increased ICSS thresholds, an effect similar to that typically seen during withdrawal from drugs of abuse. In contrast, VPA had no effects in the FST or on ICSS thresholds. This work identifies potentially important characteristics that distinguish the drugs at doses below those that produce non-specific behavioral effects, and thus serves as a basis for designing and interpreting studies of long-term treatment.

Antidepressant-like effects of cranial stimulation within a low-energy magnetic field in rats.

BACKGROUND: Evidence suggests that a novel type of magnetic resonance imaging (MRI) scan called echo planar magnetic resonance spectroscopic imaging (EP-MRSI) has mood-elevating actions in humans during the depressive phases of bipolar disorder. We examined whether a low-energy component of EP-MRSI (low-field magnetic stimulation [LFMS]) has antidepressant-like, locomotor-stimulating, or amnestic effects in rats. METHODS: We examined the effects of LFMS on immobility in the forced swim test (FST) and activity within an open field in separate groups of rats. After exposure to forced swimming, rats received LFMS (three 20-min sessions at 1.5 G/cm and .75 V/m) before behavioral testing. We also examined the effects of LFMS on fear conditioning (FC), a learning paradigm that also involves exposure to stressful conditions. RESULTS: Low-field magnetic stimulation reduced immobility in the FST, an antidepressant-like effect qualitatively similar to that of standard antidepressants. Low-field magnetic stimulation did not alter locomotor activity or FC. CONCLUSIONS: Low-field magnetic stimulation has antidepressant-like effects in rats that seem unrelated to locomotor-activating or amnestic effects. These findings raise the possibility that electromagnetic fields can affect the brain biology and might have physiologic consequences that offer novel approaches to therapy for psychiatric disorders. These same consequences might render MRI-based scans more invasive than previously appreciated.

Antidepressant-like effects of kappa-opioid receptor antagonists in the forced swim test in rats.

We showed previously that cAMP response element-binding protein (CREB) within the nucleus accumbens (NAc) of rats regulates immobility in the forced swim test (FST), an assay used to study depression. Because CREB regulates expression of dynorphin (which acts at kappa-opioid receptors) in NAc neurons, these findings raised the possibility that kappa-receptors mediate immobility behaviors in the FST. Here, we report that i.c.v. administration of the kappa-antagonist nor-binaltorphimine dose dependently decreased immobility in the FST, suggesting that it has antidepressant-like effects. Implicating a specific effect at kappa-receptors, similar antidepressant-like effects were seen after treatment with either of two novel, structurally dissimilar kappa-antagonists: 5'-guanidinonaltrindole, which was effective after i.c.v. but not systemic treatment, and 5'-acetamidinoethylnaltrindole (ANTI), which was potent and effective after systemic treatment. The behavioral effects of the kappa-antagonists resembled those of tricyclic antidepressants (desipramine) and selective serotonin reuptake inhibitors (fluoxetine and citalopram). Conversely, systemic administration of the kappa-agonist [5alpha,7alpha,8beta]-N-methyl-N-[7-[1-pyrrolidinyl]-1-oxaspiro[4.5]dec8-yl]-benzenacetamide (U-69593) dose dependently increased immobility in the FST, consistent with prodepressant-like effects. The effects of the kappa-ligands in the FST were not correlated with nonspecific effects on locomotor activity. Furthermore, the most potent and effective kappa-antagonist (ANTI) did not affect the rewarding impact of lateral hypothalamic brain stimulation at a dose with strong antidepressant-like effects. These findings are consistent with the hypothesis that CREB-mediated induction of dynorphin in the NAc "triggers" immobility behavior in the FST. Furthermore, they raise the possibility that kappa-antagonists may have efficacy as antidepressants, but lack stimulant or reward-related effects.