A Purkinje cell to parabrachial nucleus pathway enables broad cerebellar influence over the forebrain.

In addition to its motor functions, the cerebellum is involved in emotional regulation, anxiety and affect. We found that suppressing the firing of cerebellar Purkinje cells (PCs) rapidly excites forebrain areas that contribute to such functions (including the amygdala, basal forebrain and septum), but that the classic cerebellar outputs, the deep cerebellar nuclei, do not directly project there. We show that PCs directly inhibit parabrachial nuclei (PBN) neurons that project to numerous forebrain regions. Suppressing the PC-PBN pathway influences many regions in the forebrain and is aversive. Molecular profiling shows that PCs directly inhibit numerous types of PBN neurons that control diverse behaviors that are not involved in motor control. Therefore, the PC-PBN pathway allows the cerebellum to directly regulate activity in the forebrain, and may be an important substrate for cerebellar disorders arising from damage to the posterior vermis.

Infarctive Apoplexy of Previously Healthy Pituitary Glands: A Small Case Series and Literature Review.

Introduction We present two cases of suspected pituitary apoplexy found instead to be infarcted pituitary glands without histopathologic evidence of neoplastic cells, likely resulting from spontaneous infarction of previously healthy pituitary glands. Case Presentations The first case is a 55-year-old man who presented with a pulsating headache, nausea, and several months of decreased libido, polyuria, and polydipsia. Magnetic resonance imaging (MRI) revealed a rim-enhancing sellar/suprasellar mass with evidence of recent hemorrhage on the right. Testosterone, follicle-stimulating hormone, and luteinizing hormone levels were suppressed. Analysis of the resected specimen showed fibrocollagenous tissue with evidence of old hemorrhage and microscopic focus of necrotic tissue. The second case is a 56-year-old man who presented with a throbbing headache, associated nausea, and 6 weeks of polyuria and polydipsia. Testosterone levels were found to be low, and 8-hour water deprivation test showed evidence for partial diabetes insipidus. MRI revealed a mass on the right side of the pituitary gland, with evidence of likely hemorrhage on the left. Analysis of the resected specimen showed necrotic tissue without neoplastic cells. Conclusion When evaluating small pituitary lesions in patients presenting with indolent onset of pituitary insufficiency, there should be a high degree of suspicion for an infarcted pituitary gland.

High-Grade Ectopic Pituitary Adenoma within the Cerebellopontine Angle: A Case Report.

Ectopic pituitary tumors are neoplasms with no connection to the pituitary gland and are commonly deposited in other areas of the anterior skull base. A 32-year-old woman presented with a 3-month history of right-sided facial weakness, sensorineural hearing loss, diplopia, and severe headaches. Physical examination revealed a mid-dilated sluggishly reactive right pupil with slight limitation in all gazes, as well as right-sided orbicularis weakness, lagophthalmos, and decreased facial sensation. A magnetic resonance imaging (MRI) of the head without contrast revealed a 3.7 × 1.8 × 2.6 cm mildly enhancing mass in the right internal acoustic meatus and along the petrous ridge. The case was brought before the institution's tumor board, where concern for higher grade pathology, such as hemangiopericytoma, was discussed. Per patient preference, surgical biopsy of the tumor was performed. Immunohistochemical staining revealed a World Health Organization (WHO) grade II neuroendocrine tumor, with cells staining positive for synaptophysin, chromogranin, and CD56, with a K i -67 index of 8%. In addition to the ectopic location, this pituitary tumor was noted to be aggressive in nature based on its high K i -67 index. Surgical excision and radiologic therapy of tumors involving the CPA are appropriate treatments in most cases.

Medical malpractice and intracranial hemorrhages in the U.S.: An analysis of 121 cases over 35 years.

Introduction: Though all physicians are at risk for medical malpractice litigation, those in surgical specialties, particularly neurosurgeons, are at increased risk. Because intracranial hemorrhages are a life-threatening and commonly misdiagnosed condition, the aim of this study is to identify and increase awareness of factors associated with litigation in cases of intracranial hemorrhages. Methods: The online legal database Westlaw was utilized to query public litigation cases related to the management of intracranial hemorrhages between 1985 and 2020. Various search terms were used to identify cases, and the following variables were extracted: plaintiff demographics, defendant specialty, trial year, court type, location, reason for litigation, plaintiff medical complaints, trial outcomes, and payouts for both verdicts and settlements. Comparative analysis was performed between cases decided in favor of the plaintiff and in favor of the defendant. Results: A total of 121 cases met inclusion criteria. The most common type of hemorrhage was subarachnoid (65.3%), and the most common cause of hemorrhage was cerebral aneurysm/vascular malformation (37.2%). Most cases were brought against a hospital or healthcare system (60.3%), followed by emergency medicine physicians (33.1%), family medicine physicians (10.7%), and neurosurgeons (6.6%). Failure to diagnose was the most common reason for litigation (84.3%). Cases most frequently resulted in verdicts favoring the defense (48.8%), followed by settlements (35.5%). Plaintiffs were found to be significantly younger in cases ruled in favor of the plaintiff than in cases ruled in favor of the defense (p = 0.014). Cases ruled in favor of the plaintiff were also significantly more likely to involve a neurologist (p = 0.029). Conclusions: Most cases of intracranial hemorrhage resulting in malpractice litigation were classified as subarachnoid hemorrhages and caused by aneurysm/vascular malformation. Most cases were brought against hospital systems, and failure to diagnose was the most common reason for litigation. Cases resulting in verdicts in favor of the plaintiff were significantly more likely to involve younger plaintiffs and neurologists.

Cerebellum-Specific Deletion of the GABAA Receptor δ Subunit Leads to Sex-Specific Disruption of Behavior.

Granule cells (GCs) of the cerebellar input layer express high-affinity δ GABAA subunit-containing GABAA receptors (δGABAARs) that respond to ambient GABA levels and context-dependent neuromodulators like steroids. We find that GC-specific deletion of δGABAA (cerebellar [cb] δ knockout [KO]) decreases tonic inhibition, makes GCs hyperexcitable, and in turn, leads to differential activation of cb output regions as well as many cortical and subcortical brain areas involved in cognition, anxiety-like behaviors, and the stress response. Cb δ KO mice display deficits in many behaviors, but motor function is normal. Strikingly, δGABAA deletion alters maternal behavior as well as spontaneous, stress-related, and social behaviors specifically in females. Our findings establish that δGABAARs enable the cerebellum to control diverse behaviors not previously associated with the cerebellum in a sex-dependent manner. These insights may contribute to a better understanding of the mechanisms that underlie behavioral abnormalities in psychiatric and neurodevelopmental disorders that display a gender bias.

Cerebellar Purkinje cell activity modulates aggressive behavior.

Although the cerebellum is traditionally associated with balance and motor function, it also plays wider roles in affective and cognitive behaviors. Evidence suggests that the cerebellar vermis may regulate aggressive behavior, though the cerebellar circuits and patterns of activity that influence aggression remain unclear. We used optogenetic methods to bidirectionally modulate the activity of spatially-delineated cerebellar Purkinje cells to evaluate the impact on aggression in mice. Increasing Purkinje cell activity in the vermis significantly reduced the frequency of attacks in a resident-intruder assay. Reduced aggression was not a consequence of impaired motor function, because optogenetic stimulation did not alter motor performance. In complementary experiments, optogenetic inhibition of Purkinje cells in the vermis increased the frequency of attacks. These results suggest Purkinje cell activity in the cerebellar vermis regulates aggression, and further support the importance of the cerebellum in driving affective behaviors that could contribute to neurological disorders.

Silk Fibroin Films Facilitate Single-Step Targeted Expression of Optogenetic Proteins.

Optical methods of interrogating neural circuits have emerged as powerful tools for understanding how the brain drives behaviors. Optogenetic proteins are widely used to control neuronal activity, while genetically encoded fluorescent reporters are used to monitor activity. These proteins are often expressed by injecting viruses, which frequently leads to inconsistent experiments due to misalignment of expression and optical components. Here, we describe how silk fibroin films simplify optogenetic experiments by providing targeted delivery of viruses. Films composed of silk fibroin and virus are applied to the surface of implantable optical components. After surgery, silk releases the virus to transduce nearby cells and provide localized expression around optical fibers and endoscopes. Silk films can also be used to express genetically encoded sensors in large cortical regions by using cranial windows coated with a silk/virus mixture. The ease of use and improved performance provided by silk make this a promising approach for optogenetic studies.