Schizophrenia is a chronic and severe mental illness associated with substantial morbidity and mortality. Antipsychotics primarily rely on direct dopamine blockade, leading to potential life-interfering adverse events. The purpose of this review is to describe the safety and efficacy of xanomeline-trospium (CobenfyTM ), a Food and Drug Administration approved treatment for schizophrenia in adults. Xanomeline has a novel mechanism of action for the treatment of schizophrenia acting as a dual muscarinic-1 and muscarinic-4 preferring receptor agonist. Two phase 3 trials with a xanomeline-trospium up to 125 mg/30 mg 2 times daily for patients with schizophrenia saw significant reductions in PANSS positive and negative subscales, PANSS Marder negative factors, and CGI-S scale scores compared to placebo. The Cohen’s d effect for the primary endpoint was around 0.60 in both trials. The medication was well-tolerated in all clinical trials with the most common adverse events being rated as mild-to-moderate. Two long-term, open-label studies with xanomeline-trospium showed that after 52 weeks of treatment more than 75% of participants achieved a ＞ 30% improvement on PANSS total score with a mean decrease in score by 33.3 points. Other improvements were reductions in PANSS positive and negative subscales, PANSS Marder negative factor score, and CGI-S score. In both long-term studies, patients previously in the placebo groups during either phase 2 or phase 3 trials achieved a statistically significant improvement on all efficacy measures starting at week 2. These data suggest that xanomeline-trospium is an effective and well tolerated treatment for schizophrenia with a novel mechanism of action.

Schizophrenia is a chronic and severe mental illness associated with substantial morbidity and mortality. Antipsychotics primarily rely on direct dopamine blockade, leading to potential life-interfering adverse events. The purpose of this review is to describe the safety and efficacy of xanomeline-trospium (CobenfyTM ), a Food and Drug Administration approved treatment for schizophrenia in adults. Xanomeline has a novel mechanism of action for the treatment of schizophrenia acting as a dual muscarinic-1 and muscarinic-4 preferring receptor agonist. Two phase 3 trials with a xanomeline-trospium up to 125 mg/30 mg 2 times daily for patients with schizophrenia saw significant reductions in PANSS positive and negative subscales, PANSS Marder negative factors, and CGI-S scale scores compared to placebo. The Cohen’s d effect for the primary endpoint was around 0.60 in both trials. The medication was well-tolerated in all clinical trials with the most common adverse events being rated as mild-to-moderate. Two long-term, open-label studies with xanomeline-trospium showed that after 52 weeks of treatment more than 75% of participants achieved a ＞ 30% improvement on PANSS total score with a mean decrease in score by 33.3 points. Other improvements were reductions in PANSS positive and negative subscales, PANSS Marder negative factor score, and CGI-S score. In both long-term studies, patients previously in the placebo groups during either phase 2 or phase 3 trials achieved a statistically significant improvement on all efficacy measures starting at week 2. These data suggest that xanomeline-trospium is an effective and well tolerated treatment for schizophrenia with a novel mechanism of action.

Schizophrenia is a chronic and severe mental illness associated with substantial morbidity and mortality. Antipsychotics primarily rely on direct dopamine blockade, leading to potential life-interfering adverse events. The purpose of this review is to describe the safety and efficacy of xanomeline-trospium (CobenfyTM ), a Food and Drug Administration approved treatment for schizophrenia in adults. Xanomeline has a novel mechanism of action for the treatment of schizophrenia acting as a dual muscarinic-1 and muscarinic-4 preferring receptor agonist. Two phase 3 trials with a xanomeline-trospium up to 125 mg/30 mg 2 times daily for patients with schizophrenia saw significant reductions in PANSS positive and negative subscales, PANSS Marder negative factors, and CGI-S scale scores compared to placebo. The Cohen’s d effect for the primary endpoint was around 0.60 in both trials. The medication was well-tolerated in all clinical trials with the most common adverse events being rated as mild-to-moderate. Two long-term, open-label studies with xanomeline-trospium showed that after 52 weeks of treatment more than 75% of participants achieved a ＞ 30% improvement on PANSS total score with a mean decrease in score by 33.3 points. Other improvements were reductions in PANSS positive and negative subscales, PANSS Marder negative factor score, and CGI-S score. In both long-term studies, patients previously in the placebo groups during either phase 2 or phase 3 trials achieved a statistically significant improvement on all efficacy measures starting at week 2. These data suggest that xanomeline-trospium is an effective and well tolerated treatment for schizophrenia with a novel mechanism of action.

Schizophrenia is a chronic and severe mental illness associated with substantial morbidity and mortality. Antipsychotics primarily rely on direct dopamine blockade, leading to potential life-interfering adverse events. The purpose of this review is to describe the safety and efficacy of xanomeline-trospium (CobenfyTM ), a Food and Drug Administration approved treatment for schizophrenia in adults. Xanomeline has a novel mechanism of action for the treatment of schizophrenia acting as a dual muscarinic-1 and muscarinic-4 preferring receptor agonist. Two phase 3 trials with a xanomeline-trospium up to 125 mg/30 mg 2 times daily for patients with schizophrenia saw significant reductions in PANSS positive and negative subscales, PANSS Marder negative factors, and CGI-S scale scores compared to placebo. The Cohen’s d effect for the primary endpoint was around 0.60 in both trials. The medication was well-tolerated in all clinical trials with the most common adverse events being rated as mild-to-moderate. Two long-term, open-label studies with xanomeline-trospium showed that after 52 weeks of treatment more than 75% of participants achieved a ＞ 30% improvement on PANSS total score with a mean decrease in score by 33.3 points. Other improvements were reductions in PANSS positive and negative subscales, PANSS Marder negative factor score, and CGI-S score. In both long-term studies, patients previously in the placebo groups during either phase 2 or phase 3 trials achieved a statistically significant improvement on all efficacy measures starting at week 2. These data suggest that xanomeline-trospium is an effective and well tolerated treatment for schizophrenia with a novel mechanism of action.

Background: Nonaneurysmal perimesencephalic subarachnoid hemorrhage (NAPH) is a form of subarachnoid hemorrhage (SAH) occurring predominantly in the perimesencephalic region, in the absence of an aneurysm or other source of bleeding on diagnostic angiography. The underlying cause of NAPH remains unclear. Case report: Herein, we describe three patients who developed NAPH during strenuous activity in the absence of trauma after traveling to an altitude of approximately 7,500 feet. The patients were treated conservatively without any residual neurological deficits. Conclusions This case series suggests that hypoxia and vigorous exercise could be risk factors for NAPH. Patients traveling to higher altitudes should be counseled to increase their exercise intensity gradually.

The fifth edition of the World Health Organization (WHO) Classification of Central Nervous System (CNS) Tumors was released in 2021, just five years following the updated fourth edition. Advanced molecular testing such as next-generation sequencing, RNA fusion analysis, and DNA methylation profiling has led to more precise grading and classification of pre-existing tumor types as well as the recognition of new ones. Herein, we outline the major updates of the 2021 WHO Classification of CNS tumors, with emphasis on the expanded molecular characterization of CNS tumors.

Background: Nonaneurysmal perimesencephalic subarachnoid hemorrhage (NAPH) is a form of subarachnoid hemorrhage (SAH) occurring predominantly in the perimesencephalic region, in the absence of an aneurysm or other source of bleeding on diagnostic angiography. The underlying cause of NAPH remains unclear. Case report: Herein, we describe three patients who developed NAPH during strenuous activity in the absence of trauma after traveling to an altitude of approximately 7,500 feet. The patients were treated conservatively without any residual neurological deficits. Conclusions This case series suggests that hypoxia and vigorous exercise could be risk factors for NAPH. Patients traveling to higher altitudes should be counseled to increase their exercise intensity gradually.

The fifth edition of the World Health Organization (WHO) Classification of Central Nervous System (CNS) Tumors was released in 2021, just five years following the updated fourth edition. Advanced molecular testing such as next-generation sequencing, RNA fusion analysis, and DNA methylation profiling has led to more precise grading and classification of pre-existing tumor types as well as the recognition of new ones. Herein, we outline the major updates of the 2021 WHO Classification of CNS tumors, with emphasis on the expanded molecular characterization of CNS tumors.

Background: Nonaneurysmal perimesencephalic subarachnoid hemorrhage (NAPH) is a form of subarachnoid hemorrhage (SAH) occurring predominantly in the perimesencephalic region, in the absence of an aneurysm or other source of bleeding on diagnostic angiography. The underlying cause of NAPH remains unclear. Case report: Herein, we describe three patients who developed NAPH during strenuous activity in the absence of trauma after traveling to an altitude of approximately 7,500 feet. The patients were treated conservatively without any residual neurological deficits. Conclusions This case series suggests that hypoxia and vigorous exercise could be risk factors for NAPH. Patients traveling to higher altitudes should be counseled to increase their exercise intensity gradually.

The fifth edition of the World Health Organization (WHO) Classification of Central Nervous System (CNS) Tumors was released in 2021, just five years following the updated fourth edition. Advanced molecular testing such as next-generation sequencing, RNA fusion analysis, and DNA methylation profiling has led to more precise grading and classification of pre-existing tumor types as well as the recognition of new ones. Herein, we outline the major updates of the 2021 WHO Classification of CNS tumors, with emphasis on the expanded molecular characterization of CNS tumors.