Therapeutic effects of 7- to 14-day subanesthetic ketamine infusions for chronic pain on standardized psychiatric measures.

Background: We have previously shown that subanesthetic ketamine infusions effectively reduce refractory pain. However, the effects of ketamine infusions on comorbid conditions of depression and anxiety have not been explored in this patient population. Methods: We investigated the effects of ketamine on mood and anxiety in patients with refractory chronic pain treated with 7-14 days of subanesthetic continuous intravenous ketamine infusions, using well-validated clinical scales. Results: There was a significant 52% reduction in pain severity and 33% reduction in pain interference scores following ketamine treatment. Ketamine treatment also reduced scores on the depression module of the Patient Health Questionnaire (PHQ-9) by 28% and scores on the Generalised Anxiety and Depression Assessment (GAD-7) by 36%. Conclusion: Multiday subanesthetic ketamine infusions effectively reduce pain, anxiety and depression in patients with complex chronic pain.

What questions did we seek to answer? Chronic pain is a common problem with limited effective treatments. We have previously shown that supervised, multiday ketamine treatments given in the hospital can effectively reduce pain levels, with benefit for months for patients with persistent chronic pain. However, pain is quite complex and often co-occurs with other conditions, particularly depression and anxiety. We aimed to investigate how our ketamine infusions would impact these two important classes of disorder. We assessed our patients with chronic pain undergoing ketamine treatments using thoroughly researched clinical measures of pain, mood and anxiety before and after the infusions. What were the results? Patients had significant reductions in the standardized measures of pain and anxiety, and improvements in mood. We statistically checked whether these reductions were related, and found that reduced pain levels did not correlate with improvements in mood and anxiety levels. What do the results suggest? Ketamine treatments given in a carefully monitored hospital setting are effective in reducing anxiety and improving mood in patients undergoing treatment for chronic pain. The absence of a correlation between the change in pain levels and the change in anxiety and depression levels suggests that ketamine might affect different parts of the brain to achieve these independent effects.

Primary lateral sclerosis.

Like motor neuron diseases (MNDs) refer to a constellation of primarily sporadic neurodegenerative diseases characterized by a progressive loss of upper and/or lower motor neurons. Primary lateral sclerosis (PLS) is considered a neurodegenerative disorder that is characterized by a gradually progressive course affecting the central motor systems, designated by the phrase "upper motor neurons." Despite significant development in neuroimaging, neurophysiology, and molecular biology, there is a growing consensus that PLS is of unknown etiology. Currently there is no disease-modifying treatment for PLS, or prospective randomized trials being carried out, partly due to the rarity of the disease and lack of significant understanding of the underlying pathophysiology. Consequently, the approach to treatment remains largely symptomatic. In this chapter we provide an overview of primary lateral sclerosis including clinical and electrodiagnostic considerations, differential diagnosis, updates in genetics and pathophysiology, and future directions for research.

Assessment of Neurology Residency Program Websites across North America during COVID-19.

With virtual interviews for residency applications, residency program websites have become increasingly important resources for applicants. We evaluated the comprehensiveness of US and Canadian neurology residency program website, comparing this to published rankings of the best neurology and neurosurgery hospitals (for US programs) and number of residency positions (for US and Canadian programs). US program websites were found to be largely more comprehensive than Canadian websites, more extensive websites were associated with better program rankings and fewer residency seats in the US, and US regional differences in comprehensiveness were present. We recommend standardized guidelines to increase website comprehensiveness across programs.

Vertebral to Basilar Thrombus Migration Post Intravenous Thrombolysis.

Recombinant tissue plasminogen activator improves outcomes in acute ischemic stroke. Alteplase may result in thrombus migration (TM) distally to a critical arterial supply that can worsen perfusion to eloquent brain tissue. Alteplase-related stroke recanalization and clot migration in vertebral artery (VA) occlusion whereby the clot migrates to the basilar artery (BA) may be harmful. We identified seven subjects with isolated symptomatic vertebral occlusion. Two cases suffered early neurologic deterioration due to TM from VA to BA following alteplase. Precautionary transfer to thrombectomy centers may be warranted in alteplase-treated symptomatic VA occlusions in case of migration to basilar occlusion.

Clinical Reasoning: A 72-Year-Old Woman With Rapidly Progressive Bilateral Hearing Loss.

A 72-year-old woman presented with rapidly progressive hearing loss and neuropsychiatric symptoms without other focal neurologic symptoms. Progressive sequential sensorineural hearing loss (SNHL) was demonstrated on serial audiology. A diagnostic approach to SNHL is reviewed. Lumbar puncture revealed elevated protein, low glucose, and pleocytosis with poorly differentiated cells, and a differential diagnosis is discussed. MRI of the brain revealed gadolinium enhancement within the internal auditory canals bilaterally as well as the left cochlea. Zic4 antibodies were present in serum and CSF. A malignancy workup revealed right axillary lymphadenopathy. Biopsy revealed poorly differentiated breast adenocarcinoma, with identical cells to those in the CSF. The patient was treated with intrathecal methotrexate with no effect on the patient's hearing. In this case, rapidly progressive SNHL was the presenting feature of widely metastatic breast adenocarcinoma with leptomeningeal carcinomatosis, highlighting the need to search for a central cause for this presentation.

Orbital Apex Syndrome Due to Mucormycosis - Missed on Initial MRI.

A 64-year-old man with a history of diabetes mellitus and end stage renal disease presented with a several day history of cognitive decline, reduced right eye visual acuity accompanied with a complete right ophthalmoplegia in keeping with orbital apex syndrome. Initial MRI was unremarkable other than mucosal thickening in the frontal sinuses. He continued to clinically decline and repeat MRI revealed an edematous right optic nerve and a lack of enhancement within the sinuses was suspicion for invasive fungal infection. Given his history of diabetes, he was started on anti-fungal treatment and taken for debridement but passed away several days later. This case illustrates the importance of the orbital apex syndrome as a localization. Mucormycosis should be considered in acute onset ophthalmoplegia particularly in patients with diabetes and diabetic ketoacidosis. Empiric anti-fungal therapy should be started early for suspected rhino-orbital cerebral mucormycosis, although mortality remains high despite treatment.

The effects of a multiday (10-14 days) subanesthetic dose IV ketamine infusion in the treatment of refractory chronic pain.

Aim: Ketamine is an anesthetic agent that at lower doses can be a potent analgesic. There has been an interest in the use of low dose ketamine in treatment of chronic pain syndromes. Patients & methods: We report the results of a retrospective observational study for patients diagnosed with a chronic noncancer pain syndrome receiving a 2-week continuous subanesthetic IV ketamine infusion. Results & conclusion: We conclude that a 10-14 days of subanesthetic ketamine infusion in chronic patients results in clinically significant lowering of patients' numerical pain score. Further studies looking at subanesthetic ketamine infusion in a prospective trial of multi-day IV ketamine infusion in chronic refractory chronic neuropathic pain are needed to further assess the efficacy of ketamine.

Ketamine is a pharmacological agent that was developed in the 1960s. There has been an increase in interest in the use of ketamine at low doses in the treatment of chronic pain syndromes. In this study, we report the results of a study that investigated patients diagnosed with a chronic noncancer pain syndrome that received a 2-week continuous ketamine infusion. We hypothesized that patients receiving IV ketamine infusion will experience acute and chronic lowering of pain intensity on the numerical rating pain level scale and reduce patient's opioid requirements. We concluded that a 10­14 day of subanesthetic ketamine infusion in chronic patients results in clinically significant lowering of patients' numerical pain score during the ketamine infusion.

Immune checkpoint inhibitor-induced encephalitis with dostarlimab in two patients: Case series.

Immune checkpoint inhibitors (ICIs) are being used increasingly in the treatment of several cancers and have been associated with neurological complications including immune checkpoint inhibitor-induced encephalitis (ICI-iE). We present two cases of ICI-iE with the novel agent dostarlimab, which to our knowledge are the first reported with this agent. These cases add to the growing body of literature on ICI-iE, demonstrating two cases of meningoencephalitis associated with the novel agent dostarlimab treated successfully with prednisone. As imaging studies may be unrevealing, clinicians must maintain a high index of suspicion for ICI-iE in any patient who develops altered mental status on ICI therapy, with low threshold to obtain lumbar puncture for evidence of inflammatory CSF and to exclude other causes. It is important to note that many neurological presentations of ICIs can also be secondary to tumor metastasis and other paraneoplastic syndromes, making the diagnosis challenging. Prognosis can be good with early recognition and treatment with corticosteroids. Whether patients can be rechallenged with ICI is to be determined in larger studies given the rarity of this complication.

Tardive neurotoxicity of anticholinergic drugs: A review.

The cholinergic system is a complex neurotransmitter system with functional involvement at multiple levels of the nervous system including the cerebral cortex, spinal cord, autonomic nervous system, and neuromuscular junction. Anticholinergic medications are among the most prescribed medications, making up one-third to one-half of all medications prescribed for seniors. Recent evidence has linked long-term use of anticholinergic medications and dementia. Emerging evidence implicates the cholinergic system in the regulation of cerebral vasculature as well as neuroinflammation, suggesting that anticholinergic medications may contribute to absolute risk and progression of neurodegenerative diseases. In this review, we explore the involvement of the cholinergic system in various neurodegenerative diseases and the possible detrimental effects of anticholinergic medications on the onset and progression of these disorders. We identified references by searching the PubMed and Cochrane database between January 1990 and September 2019 for English-language animal and human studies including randomized clinical trials (RCTs), meta-analyses, systematic reviews, and observational studies. In addition, we conducted a manual search of reference lists from retrieved studies. Long-term anticholinergic medication exposure may have detrimental consequences beyond well-documented short-term cognitive effects, through a variety of mechanisms either directly impacting cholinergic neurotransmission or through receptors expressed on the vasculature or immune cells, providing a pathophysiological framework for complex interactions across the entire neuroaxis.

Therapeutic Hypothermia in Acute Ischemic Stroke-a Systematic Review and Meta-Analysis.

PURPOSE OF REVIEW: Therapeutic hypothermia (TH) in stroke demonstrates robust neuroprotection in animals but clinical applications remain controversial. We assessed current literature on the efficacy of TH in ischemic stroke. RECENT FINDINGS: We conducted a meta-analysis comparing TH versus controls in studies published until June 2019. Controlled studies reporting on ≥ 10 adults with acute ischemic stroke were included. Primary outcome was functional independence (modified Rankin Scale [mRS] ≤ 2). Twelve studies (n = 351 TH, n = 427 controls) were included. Functional independence did not differ between groups (RR 1.17, 95% CI 0.93-1.46, random-effects p = 0.2). Five studies reported individual mRS outcomes and demonstrated a shift toward better outcome with TH (unadjusted cOR 1.57, 95% CI 1.01-2.44, p = 0.05). Overall complications were higher with TH (RR 1.18, 95% CI 1.06-1.32, p < 0.01). We did not observe an overall beneficial effect of TH in this analysis although some studies showed a shift toward better outcome. TH was associated with increased complications.

Outcome of stroke patients on clopidogrel plus proton-pump inhibitors: a single-center cohort study.

BACKGROUND: Recent studies suggest a higher risk of adverse cardiovascular outcome and mortality in patients co-prescribed clopidogrel with proton pump inhibitors (PPI). OBJECTIVE: Investigate the impact of concomitant prescription of clopidogrel and PPI on 30-day unplanned readmission and one-year all-cause mortality. DESIGN: Retrospective longitudinal cohort study. SETTING: Single academic tertiary center. PATIENTS AND METHODS: The study included patients admitted with a diagnosis of ischemic or hemorrhagic stroke between 2010 and 2014. Demographic and outcome data were collected and compared for patients on clopidogrel plus PPI vs those on clopidogrel plus H2blockers and those not on clopidogrel. MAIN OUTCOME MEASURES: One-year mortality and 30-day unplanned readmissions were compared among different patient groups using multivariable logistic regression modeling. SAMPLE SIZE: 464 patients. RESULTS: Out of 464 patients, 175 (37.7%) were discharged on clopidogrel. The concomitant prescription of clopidogrel and PPI was noted in 107 (24.4%) and clopidogrel and H2 blockers in 36 patients (7.8%). The one-year all-cause mortality in the entire cohort was 22.2%. Patients on clopidogrel plus PPI did not have a higher risk of one-year mortality compared to the non-PPI cohort (6.2% vs. 4.8%, p 0.7). There was a non-significant suggestion of lower one-year mortality in patients on clopidogrel plus PPI vs those not on clopidogrel (6.2% vs. 10.1%, p 0.23). In multivariable logistic regression, the use of clopidogrel plus PPI did not predict higher one-year mortality (odds ratio 0.6, P=0.6). The risk of unplanned 30-day readmission was lower in those with clop-idogrel plus PPI (odds ratio 0.6, P=.03). CONCLUSION: The use of clopidogrel plus PPI resulted in lower readmission rates and was not associated with higher mortality compared with the non-PPI cohorts. LIMITATIONS: Single center study, not generalizable. Given the retrospective nature of this study, we did not collect data on duration of treatments or patient compliance. CONFLICT OF INTEREST: None.