Global uncertainty in the diagnosis of neurological complications of SARS-CoV-2 infection by both neurologists and non-neurologists: An international inter-observer variability study.

INTRODUCTION: Uniform case definitions are required to ensure harmonised reporting of neurological syndromes associated with SARS-CoV-2. Moreover, it is unclear how clinicians perceive the relative importance of SARS-CoV-2 in neurological syndromes, which risks under- or over-reporting. METHODS: We invited clinicians through global networks, including the World Federation of Neurology, to assess ten anonymised vignettes of SARS-CoV-2 neurological syndromes. Using standardised case definitions, clinicians assigned a diagnosis and ranked association with SARS-CoV-2. We compared diagnostic accuracy and assigned association ranks between different settings and specialties and calculated inter-rater agreement for case definitions as "poor" (κ ≤ 0.4), "moderate" or "good" (κ > 0.6). RESULTS: 1265 diagnoses were assigned by 146 participants from 45 countries on six continents. The highest correct proportion were cerebral venous sinus thrombosis (CVST, 95.8%), Guillain-Barré syndrome (GBS, 92.4%) and headache (91.6%) and the lowest encephalitis (72.8%), psychosis (53.8%) and encephalopathy (43.2%). Diagnostic accuracy was similar between neurologists and non-neurologists (median score 8 vs. 7/10, p = 0.1). Good inter-rater agreement was observed for five diagnoses: cranial neuropathy, headache, myelitis, CVST, and GBS and poor agreement for encephalopathy. In 13% of vignettes, clinicians incorrectly assigned lowest association ranks, regardless of setting and specialty. CONCLUSION: The case definitions can help with reporting of neurological complications of SARS-CoV-2, also in settings with few neurologists. However, encephalopathy, encephalitis, and psychosis were often misdiagnosed, and clinicians underestimated the association with SARS-CoV-2. Future work should refine the case definitions and provide training if global reporting of neurological syndromes associated with SARS-CoV-2 is to be robust.

Ureteroscopy in Patients Taking Anticoagulant or Antiplatelet Therapy: Practice Patterns and Outcomes in a Surgical Collaborative.

PURPOSE: AUA guidelines recommend ureteroscopy as first line therapy for patients on anticoagulant or antiplatelet therapy and advocate using a ureteral access sheath. We examined practice patterns and unplanned health care use for these patients in Michigan. MATERIALS AND METHODS: Using the Michigan Urological Surgery Improvement Collaborative (MUSIC) clinical registry we identified ureteroscopy cases from 2016 to 2019. We assessed outcomes and adherence to guidelines based on therapy at time of ureteroscopy: 1) anticoagulant: continuous warfarin or novel oral agent therapy; 2) antiplatelet: continuous clopidogrel or aspirin therapy; 3) control: not on anticoagulant/antiplatelet therapy. We fit multivariate models to assess anticoagulant or antiplatelet therapy association with emergency department visits, hospitalization and ureteral access sheath use. RESULTS: In total, 9,982 ureteroscopies were performed across 31 practices with 3.1% and 7.8% on anticoagulant and antiplatelet therapy, respectively. There were practice (0% to 21%) and surgeon (0% to 35%) variations in performing ureteroscopy on patients on anticoagulant/antiplatelet therapy regardless of volume. After adjusting for risk factors, anticoagulant or antiplatelet therapy was not associated with emergency department visits. Hospitalization rates in anticoagulant, antiplatelet and control groups were 4.3%, 5.5% and 3.2%, respectively, and significantly increased with antiplatelet therapy (OR 1.48, 95% CI 1.02-2.14). Practice-level ureteral access sheath use varied (23% to 100%) and was not associated with anticoagulant/antiplatelet therapy. Limitations include inability to risk stratify between type/dosage of anticoagulant/antiplatelet therapy. CONCLUSIONS: We found practice-level and surgeon-level variation in performing ureteroscopy while on anticoagulant/antiplatelet therapy. Ureteroscopy on anticoagulant is safe. However, antiplatelet therapy increases the risk of hospitalization. Despite guideline recommendations, ureteral access sheath use is not associated with anticoagulant/antiplatelet therapy.

Acute Cytotoxic and Vasogenic Edema after Subarachnoid Hemorrhage: A Quantitative MRI Study.

BACKGROUND AND PURPOSE: The mechanism of early brain injury following subarachnoid hemorrhage is not well understood. We aimed to evaluate if cytotoxic and vasogenic edema are contributing factors. MATERIALS AND METHODS: A retrospective analysis was conducted in patients with SAH undergoing diffusion-weighted MR imaging within 72 hours of onset. Apparent diffusion coefficient values derived from DWI were evaluated by using whole-brain histograms and 19 prespecified ROIs in patients with SAH and controls with normal findings on MRI. Cytotoxic edema observed outside the ROIs was assessed in patients with SAH. The average median ADC values were compared between patients with SAH and controls and patients with SAH with mild (Hunt and Hess 1-3) versus severe early brain injury (Hunt and Hess 4-5). RESULTS: We enrolled 33 patients with SAH and 66 controls. The overall average median whole-brain ADC was greater for patients with SAH (808 × 10-6 mm2/s) compared with controls (788 × 10-6 mm2/s, P < .001) and was higher in patients with SAH across ROIs after adjusting for age: cerebral gray matter (826 versus 803 × 10-6 mm2/s, P = .059), cerebral white matter (793 versus 758 × 10-6 mm2/s, P = .023), white matter tracts (797 versus 739 × 10-6 mm2/s, P < .001), and deep gray matter (754 versus 713 × 10-6 mm2/s, P = .016). ADC values trended higher in patients with Hunt and Hess 4-5 versus those with Hunt and Hess 1-3. Early cytotoxic edema was observed in 13 (39%) patients with SAH and was more prevalent in those with severe early brain injury (87.5% of patients with Hunt and Hess 4-5 versus 24.0% of those with Hunt and Hess 1-3, P = .001). CONCLUSIONS: Age-adjusted ADC values were globally increased in patients with SAH compared with controls, even in normal-appearing brain regions, suggesting diffuse vasogenic edema. Cytotoxic edema was also present in patients with SAH and correlated with more severe early brain injury.

Neurologic complications of acute environmental injuries.

Environmental injuries can result in serious neurologic morbidity. This chapter reviews neurologic complications of thermal burns, smoke inhalation, lightning strikes, electric injury, near drowning, decompression illness, as well as heat stroke and accidental hypothermia. Knowing the pathophysiology and clinical presentation of such injuries is essential to proper management of primary and secondary medical complications. This chapter highlights the most frequently encountered neurologic injuries secondary to common environmental hazards, divided into the topics: injuries related to fire, electricity, water, and the extremes of temperature.

Neural regeneration dynamics of Xenopus laevis olfactory epithelium after zinc sulfate-induced damage.

Neural stem cells (NSCs) of the olfactory epithelium (OE) are responsible for tissue maintenance and the neural regeneration after severe damage of the tissue. In the normal OE, NSCs are located in the basal layer, olfactory receptor neurons (ORNs) mainly in the middle layer, and sustentacular (SUS) cells in the most apical olfactory layer. In this work, we induced severe damage of the OE through treatment with a zinc sulfate (ZnSO4) solution directly in the medium, which resulted in the loss of ORNs and SUS cells, but retention of the basal layer. During recovery following injury, the OE exhibited increased proliferation of NSCs and rapid neural regeneration. After 24h of recovery, new ORNs and SUS cells were observed. Normal morphology and olfactory function were reached after 168h (7 days) of recovery after ZnSO4 treatment. Taken together, these data support the hypothesis that NSCs in the basal layer activate after OE injury and that these are sufficient for complete neural regeneration and olfactory function restoration. Our analysis provides histological and functional insights into the dynamics between olfactory neurogenesis and the neuronal integration into the neuronal circuitry of the olfactory bulb that restores the function of the olfactory system.

Degree of Collaterals and Not Time Is the Determining Factor of Core Infarct Volume within 6 Hours of Stroke Onset.

BACKGROUND AND PURPOSE: Growth of the core infarct during the first hours of ischemia onset is not well-understood. We hypothesized that factors other than time from onset of ischemia contribute to core infarct volume as measured by MR imaging. MATERIALS AND METHODS: Prospectively collected clinical and imaging data of consecutive patients with stroke presenting between March 2008 and April 2013 with anterior circulation large-vessel occlusion and MR imaging performed within 6 hours from the time of onset were reviewed. The association of time from onset, clinical, and radiographic features with DWI volume was assessed by using χ(2) and Mann-Whitney U tests. RESULTS: Of 91 patients, 21 (23%) underwent MR imaging within 0-3 hours from onset, and 70 (76%), within 3-6 hours. Median MR imaging infarct volume was similar in both timeframes, (24.7 versus 29.4 mL, P = .906), and there was no difference in the proportion of patients with large infarct volumes (≥70 mL, 23.8% versus 22.8%, P = .928). Using receiver operating characteristic analysis, we detected no association between the time from onset and MR imaging infarct volume (area under the curve = 0.509). In multivariate analysis, CTA collaterals (>50% of the territory) (adjusted OR, 0.192; 95% CI, 0.04-0.9; P = .046), CTA ASPECTS (adjusted OR, 0.464; 95% CI, 0.3-0.8; P = .003), and a history of hyperlipidemia (adjusted OR, 11.0; 95% CI, 1.4-88.0; P = .023) (but not time from stroke onset to imaging) were independent predictors of MR imaging infarct volume. CONCLUSIONS: Collateral status but not time from stroke onset to imaging was a predictor of the size of core infarct in patients with anterior circulation large-vessel occlusion presenting within 6 hours from onset.

One-year monitoring of an oligonucleotide fluorescence in situ hybridization probe panel laboratory-developed test for bladder cancer detection.

BACKGROUND: Previously, we had developed and manufactured an oligonucleotide fluorescence in situ hybridization (OligoFISH) probe panel based on the most clinically sensitive chromosomes found in a reference set of bladder carcinoma cases. The panel was clinically validated for use as a diagnostic and monitoring assay for bladder cancer, reaching 100% correlation with the results of the UroVysion test. After 1 year of using this probe panel, we present here the comparison of cytology, cystoscopy, and pathology findings to the OligoFISH probe panel results to calculate its clinical performance. MATERIALS AND METHODS: In order to calculate clinical performance, we compared the OligoFISH results to the cytology and cystoscopy/pathology findings for 147 initial diagnoses and 399 recurrence monitorings. Finally, we compared clinical performance to published values for the UroVysion test, including both low- and high-grade tumors. RESULTS: Chromosomes 3, 6, 7, and 20 were highly involved in bladder carcinoma aneuploidy. At the initial diagnosis, we obtained 90.5% (95% confidence interval [CI]: 84.5%-94.7%) accuracy, 96.8% sensitivity (95% CI: 91.0%-99.3%), 79.2% specificity (95% CI: 65.9%-87.8%), 89.2% positive predictive value (PPV; 95% CI: 81.5%-94.5%), and 93.3% negative predictive value (NPV; 95% CI: 81.7%-97.3%). When monitoring for recurrence, we obtained 85.2% accuracy (95% CI: 81.3%-88.5%), 82.0% sensitivity (95% CI: 76.0%-87.1%), 88.4% specificity (95% CI: 83.2%-92.5%), 87.7% PPV (95% CI: 82.1%-92.0%), and 83.0% NPV (95% CI: 77.3%-87.8%). When looking at low- and high-grade tumors, the test showed 100% sensitivity for high-grade tumors (95% CI: 92.5%-100%) and 87.5% sensitivity (95% CI: 68.8%-95.5%) for low-grade tumors. All the clinical parameters for the OligoFISH panel were higher than the UroVysion test's published performance. We found significantly higher clinical sensitivity and NPV at initial diagnosis and significantly higher specificity and PPV for recurrence. CONCLUSION: The OligoFISH probe panel is a fast, easy, and reproducible test for bladder cancer diagnosis and monitoring, with excellent clinical performance and utility.

Pediatric idiopathic transverse myelitis presenting as an anterior cord syndrome: a case report.

OBJECTIVES: Describe the case of an Anterior Cord Syndrome secondary to transverse myelitis. ANTERIOR CORD SYNDROME: Anterior Cord syndrome (ACS) is characterized by a lesion that affects the anterior two thirds of the spinal cord while preserving the posterior columns. TRANSVERSE MYELITIS: Transverse myelitis (TM) is an inflammatory disorder with a heterogeneous pathogenesis affecting the spinal cord at one or more segments, resulting in motor, sensory, and autonomic dysfunction in the absence of a preexisting neurological disease or spinal cord compression. TREATMENT: The patient was treated with methylprednisolone, IV Antibiotics, acyclovir, and inpatient rehabilitation. REHABILITATION: The patient significantly improved her function throughout inpatient rehabilitation and was discharged after achieving modified independent level with ambulation and all activities of daily living. The patient also gained independence with an intermittent catheterization program and a nightly bowel program, which included suppository and digital stimulation. CONCLUSIONS: This case illustrates the first documented pediatric patient with a unique case of Anterior Cord Syndrome caused by idiopathic transverse myelitis.

Seizures after Onyx embolization for the treatment of cerebral arteriovenous malformation.

Onyx embolization of cerebral arteriovenous malformations (AVM) has become increasingly common. We explored the risk of seizures after Onyx use.A retrospective review was conducted of 20 patients with supratentorial brain arteriovenous malformation (AVM) who received Onyx embolization between 2006 and 2009. Baseline demographics, clinical history, seizure history, AVM characteristics and treatment were compared between those who developed post-onyx seizure and those who did not. MRIs were reviewed for edema following Onyx treatment.Of 20 patients who underwent Onyx embolization, the initial AVM presentation was hemorrhage in 40% (N=8). The median number of embolizations was two (range 1-4) and the median final obliteration amount was 90% (range 50-100%). A history of seizure was present in 50% (N=10) of patients pre-embolization and 12 (60%) patients received seizure medications (treatment or prophylaxis) prior to embolization. Seizur post-Onyx embolization occurred in 45% (N=9). The median time to seizur post-Onyx was seven days (range 0.3-210). Four patients (20%) with seizures post-Onyx had no seizure history. Two of these patients (10%) had no other identifiable cause for seizure other than recent Onyx embolization. Seizures in these two patients occurred within 24 hours of Onyx administration. Among patients with post-Onyx seizures, there was a trend toward larger AVM size (P=0.091) and lower percent obliteration (P=0.062). Peri-AVM edema was present in 75% of MRIs performed within one month of Onyx treatment and may represent a possible etiology for seizures.New onset seizures post-Onyx embolization are not uncommon. Further study of seizure prevention is warranted.

Electrographic seizures and periodic discharges after intracerebral hemorrhage.

OBJECTIVE: To determine the frequency and significance of electrographic seizures and other EEG findings in patients with intracerebral hemorrhage (ICH). METHODS: We reviewed 102 consecutive patients with ICH who underwent continuous electroencephalographic monitoring (cEEG). Demographic, clinical, radiographic, and cEEG findings were recorded. Using multivariate logistic regression analysis, we determined factors associated with 1) electrographic seizures, 2) periodic epileptiform discharges (PEDs), and 3) poor outcome (death, vegetative or minimally conscious state) at hospital discharge. RESULTS: Seizures occurred in 31% (n = 32) of patients with ICH, prior to cEEG in 19 patients. Eighteen percent (n = 18) of patients had electrographic seizures; only one of these patients also had clinical seizures while on cEEG. After controlling for demographic and clinical predictors, only an increase in ICH volume of 30% or more between admission and 24-hour follow-up CT scan was associated with electrographic seizures (33% vs 15%; OR 9.5, 95% CI 1.7 to 53.8). PEDs were less frequently seen in those with hemorrhages located at least 1 mm from the cortex (8% vs 29%; OR 0.2, 95% CI 0.1 to 0.7). PEDs were independently associated with poor outcome (65% vs 17%; OR 7.6, 95% CI 2.1 to 27.3). In patients with electrographic seizures, the first seizure was detected within the first hour of cEEG monitoring in 56% and within 48 hours in 94%. CONCLUSIONS: Seizures occurred in one third of patients with intracerebral hemorrhage (ICH) and over half were purely electrographic. Electrographic seizures were associated with expanding hemorrhages, and periodic discharges with cortical ICH and poor outcome. Further research is needed to determine if treating or preventing seizures or PEDs might lead to improved outcome after ICH.

Cerebrovascular reactivity and vasospasm after subarachnoid hemorrhage: a pilot study.

The authors performed serial transcranial Doppler (TCD) and carbon dioxide reactivity (CO2R) testing in 20 aneurysmal subarachnoid hemorrhage patients to determine whether impaired cerebrovascular reactivity was associated with symptomatic vasospasm. Symptomatic vasospasm occurred in 9 of 14 patients with abnormal CO2R and in none of 6 patients with preserved reactivity (p = 0.011). Abnormal CO2R preceded the onset of vasospasm in 7 of 9 patients. Abnormal standard TCD testing was not associated with vasospasm.

Effect of crown ethers on structure, stability, activity, and enantioselectivity of subtilisin Carlsberg in organic solvents.

Colyophilization or codrying of subtilisin Carlsberg with the crown ethers 18-crown-6, 15-crown-5, and 12-crown-4 substantially improved enzyme activity in THF, acetonitrile, and 1,4-dioxane in the transesterification reactions of N-acetyl-L-phenylalanine ethylester and 1-propanol and that of (+/-)-1-phenylethanol and vinylbutyrate. The acceleration of the initial rate, V(0), ranged from less than 10-fold to more than 100-fold. All crown ethers activated subtilisin substantially, which excludes a specific macrocyclic effect from being responsible. The secondary structure of subtilisin was studied by Fourier-transform infrared (FTIR) spectroscopy. 18-Crown-6 and 15-crown-5 led to a more nativelike structure of subtilisin in the organic solvents employed when compared with that of the dehydrated enzyme obtained from buffer alone. However, the high level of activation with 12-crown-4 where this effect was not observed excluded overall structural preservation from being the primary cause of the observed enzyme activation. The conformational mobility of subtilisin was investigated by performing thermal denaturation experiments in 1,4-dioxane. Although only a small effect of temperature on subtilisin structure was observed for the samples prepared with or without 12-crown-4, both 18-crown-6 and 15-crown-5 caused the enzyme to denature at quite low temperatures (38 degrees C and 56 degrees C, respectively). No relationship between this property and V(0) was evident, but increased conformational mobility of the protein decreased its storage stability. The possibility of a "molecular imprinting" effect was also tested by removing 18-crown-6 from the subtilisin-18-crown-6 colyophilizate by washing. V(0) was only halved as a result of this procedure, an effect insignificant compared with the ca. 80-fold rate enhancement observed prior to washing in THF. This suggests that molecular imprinting is likely the primary cause of subtilisin activation by crown ethers, as recently suggested.

[Erotic hallucinations associated with the use of propofol]. / Alucinaciones eróticas asociadas al uso de propofol.

A 42-year-old woman underwent outpatient surgery to remove vocal cord polyps. She had a history of depressive syndrome and had previously undergone surgery without complications. Before surgery she received 3.5 mg of midazolam orally. General anesthesia was provided with propofol: one initial bolus of 1 mg/kg followed by an infusion of 6 mg/kg/h. Surgery was uneventful. Upon arrival in the postanesthetic recovery ward, the patient, greatly agitated, accused the orderlies pushing the gurney of forcing her to touch his genitals. Twenty-four hours after surgery she did not remember the incident. Since 1987 various cases of postoperative sexual hallucination have been associated with the use of propofol. Usually the patients are women undergoing minor gynecological procedures and involve male health-care providers in the surgical area. The incidents are characteristically followed by amnesia. This clinical picture has also been described for midazolam and nitrous oxide, but the frequency is higher for propofol owing to its pharmacodynamic and pharmacokinetic properties (rapidly recovered awareness and lowering of inhibition). Given the legal implications, the presence of someone of the same sex as the patient is recommended when the patient awakens.

Right-side endocarditis in injection drug users: review of proposed mechanisms of pathogenesis.

Infective endocarditis of the right-side heart valves occurs commonly in injection drug users. Although a variety of hypotheses have been put forward to explain this clinical observation, no single hypothesis is adequate. In this article, basic scientific, clinical, and microbiological data on this topic are presented. It is apparent that no clear unifying mechanism emerges to explain the well-documented clinical predilection for the infection of the right-side heart valves in this population. Further investigation of this topic utilizing large international clinical registries may help to clarify matters further.

[Accidental catheterization of the subdural space. Confirmation by radiological study]. / Cateterización accidental del espacio subdural. Confirmación por estudio radiológico.

We report two cases of accidental subdural blockade after peridural anesthesia. The blockade was detected postoperatively in both cases, two hours after start of continuous perfusion in one patient and eight hours afterwards in the other. Subdural diffusion was confirmed after injection of a radiopaque contrast medium. Subdural blockade usually manifests as an extensive neural block that is disproportionate to the amount of anesthetic injected. We discuss the need for frequent monitoring of metameric, sensory and motor levels to detect possible catheter misplacement, in addition to routine monitoring of heart rate, arterial pressure and oxygen saturation. When subdural blockade is suspected, epidural perfusion should be discontinued in order to prevent extensive sensory and motor blocks. A firm diagnosis can only be made by X-ray. A simple radiograph may adequately demonstrate subdural placement in some cases, although computed axial tomography should be performed when doubt arises.

Immediate primary realignment of prostatomembranous urethral disruptions using endourologic techniques.

OBJECTIVES: A new technique is described for primary realignment of prostatomembranous urethral disruptions using endourologic techniques. METHODS: Realignment was achieved in 3 patients on the day of injury. Primary urethral realignment is achieved by passing a council-tip catheter over a guidewire inserted during antegrade flexible cystourethroscopy. RESULTS: Three patients underwent successful realignment on the day of injury. With an average follow-up of 6 months, 2 patients are voiding spontaneously without evidence of a urethral stricture; 1 patient developed a structure necessitating delayed urethroplasty. All patients have retained their potency and continence. CONCLUSIONS: Our technique provides an expeditious, simple, and atraumatic means of obtaining primary realignment of acute prostatomembranous urethral disruptions.

Cayo Santiago and the laboratory of perinatal physiology: recollections.

Interest in comparative vertebrate neuroanatomy moved the author's plea for the continuation of the Cayo Santiago monkey colony when it was put for sale in 1947. Grants from the National Institutes of Health permitted its precarious subsistence until the mid 1950s, when a casual meeting with the Director of the Laboratory of Neuroanatomical Sciences in Bethesda aroused the latter's interest. Through his efforts the National Institute of Neurological Diseases and Blindness solved the macaques' plight and established the Laboratory of Perinatal Physiology in collaboration with the University of Puerto Rico School of Medicine. Events of this venture are narrated from the author's participation and additional information in his file. Anecdotes are related as a background of the growth and development of the project until the early 1960s when the author's association with it came to an end.