Classics in Chemical Neuroscience: Selegiline, Isocarboxazid, Phenelzine, and Tranylcypromine.

The discovery of monoamine oxidase inhibitors (MAOIs) in the 1950s marked a significant breakthrough in medicine, creating a powerful new category of drug: the antidepressant. In the years and decades that followed, MAOIs have been used in the treatment of several pathologies including Parkinson's disease, Alzheimer's disease, and various cancers and as anti-inflammatory agents. Despite once enjoying widespread use, MAOIs have dwindled in popularity due to side effects, food-drug interactions, and the introduction of other antidepressant drug classes such as tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs). The recently published prescriber's guide for the use of MAOIs in treating depression has kindled a resurgence of their use in the clinical space. It is therefore timely to review key aspects of the four "classic" MAOIs: high-dose selegiline, isocarboxazid, phenelzine, and tranylcypromine. This review discusses their chemical synthesis, metabolism, pharmacology, adverse effects, and the history and importance of these drugs within the broader field of chemical neuroscience.

Minimally invasive pericranial flap harvest through a supraorbital eyebrow craniotomy: Technical note in salvage skull base reconstruction.

BACKGROUND AND IMPORTANCE: The supraorbital eyebrow craniotomy is a minimally invasive approach that provides access to pathologies of the anterior and middle cranial fossae. Vascularized flaps are preferred when considering reconstructive options, however, small incisions may not provide adequate access to vascularized tissue. We present two cases demonstrating a modified technique for harvesting pericranium through an eyebrow supraorbital craniotomy for reconstruction of large skull base defects. CLINICAL PRESENTATION: The first case is of a 62-year-old woman with an invasive esthesioneuroblastoma. Multiple resections and reconstructions, including a large frontal craniectomy and titanium mesh cranioplasty, resulted in refractory tension pneumocephalus. A supraorbital craniotomy was performed with endoscope-assisted harvesting of a pericranial flap through a coronal plane stab incision for definitive repair. The second case is a 44-year-old woman with a high-grade neuroendocrine tumor transgressing the anterior cranial fossa. Resection was achieved via combined supraorbital eyebrow craniotomy and endoscopic endonasal approach. A multilayered reconstruction including a pericranial flap from above and a nasoseptal flap from below was used to reconstruct the defect. The pericranial flap was again harvested with endoscope assistance through a coronal plane stab incision. Both cases had excellent outcomes with no post-operative cerebrospinal fluid leak. CONCLUSION: Repair of large anterior cranial fossa defects with a vascularized pericranial flap can be performed through a supraorbital eyebrow craniotomy. Utilizing small, strategically placed transverse (coronal plane) incisions behind the hairline allows for the endoscope-assisted harvesting of a highly customized flap. This modified technique increases the flexibility of the minimally invasive supraorbital craniotomy.

Neuropathology of COVID-19 (neuro-COVID): clinicopathological update.

Coronavirus disease 2019 (COVID-19) is emerging as the greatest public health crisis in the early 21stcentury. Its causative agent, Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), is an enveloped single stranded positive-sense ribonucleic acid virus that enters cells via the angiotensin converting enzyme 2 receptor or several other receptors. While COVID-19 primarily affects the respiratory system, other organs including the brain can be involved. In Western clinical studies, relatively mild neurological dysfunction such as anosmia and dysgeusia is frequent (~70-84%) while severe neurologic disorders such as stroke (~1-6%) and meningoencephalitis are less common. It is unclear how much SARS-CoV-2 infection contributes to the incidence of stroke given co-morbidities in the affected patient population. Rarely, clinically-defined cases of acute disseminated encephalomyelitis, Guillain-Barré syndrome and acute necrotizing encephalopathy have been reported in COVID-19 patients. Common neuropathological findings in the 184 patients reviewed include microglial activation (42.9%) with microglial nodules in a subset (33.3%), lymphoid inflammation (37.5%), acute hypoxic-ischemic changes (29.9%), astrogliosis (27.7%), acute/subacute brain infarcts (21.2%), spontaneous hemorrhage (15.8%), and microthrombi (15.2%). In our institutional cases, we also note occasional anterior pituitary infarcts. COVID-19 coagulopathy, sepsis, and acute respiratory distress likely contribute to a number of these findings. When present, central nervous system lymphoid inflammation is often minimal to mild, is detected best by immunohistochemistry and, in one study, indistinguishable from control sepsis cases. Some cases evince microglial nodules or neuronophagy, strongly supporting viral meningoencephalitis, with a proclivity for involvement of the medulla oblongata. The virus is detectable by reverse transcriptase polymerase chain reaction, immunohistochemistry, or electron microscopy in human cerebrum, cerebellum, cranial nerves, olfactory bulb, as well as in the olfactory epithelium; neurons and endothelium can also be infected. Review of the extant cases has limitations including selection bias and limited clinical information in some cases. Much remains to be learned about the effects of direct viral infection of brain cells and whether SARS-CoV-2 persists long-term contributing to chronic symptomatology.

Procurement and Storage of Surgical Biospecimens.

A biobank is an important nexus between clinical and research aspects of pathology. The collection and storage of high quality surgical samples is essential for diagnosis post-surgery, and can also be used to create vaccines, identify therapeutic targets or establish eligibility of cancer patients in a clinical trial. Therefore, personnel handling surgical tissues should follow standard operating procedures (SOP) to maximize efficiency and preserve tissue quality. This chapter is intended to familiarize novice biobank personnel with the issues associated with different steps of surgical tissue collection including patient consent, sample collection, tissue storage, quality control, and distribution.