Brain and Lung Imaging Correlation in Patients with COVID-19: Could the Severity of Lung Disease Reflect the Prevalence of Acute Abnormalities on Neuroimaging? A Global Multicenter Observational Study.

PURPOSE: Our aim was to study the association between abnormal findings on chest and brain imaging in patients with coronavirus disease 2019 (COVID-19) and neurologic symptoms. MATERIALS AND METHODS: In this retrospective, international multicenter study, we reviewed the electronic medical records and imaging of hospitalized patients with COVID-19 from March 3, 2020, to June 25, 2020. Our inclusion criteria were patients diagnosed with Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) infection with acute neurologic manifestations and available chest CT and brain imaging. The 5 lobes of the lungs were individually scored on a scale of 0-5 (0 corresponded to no involvement and 5 corresponded to >75% involvement). A CT lung severity score was determined as the sum of lung involvement, ranging from 0 (no involvement) to 25 (maximum involvement). RESULTS: A total of 135 patients met the inclusion criteria with 132 brain CT, 36 brain MR imaging, 7 MRA of the head and neck, and 135 chest CT studies. Compared with 86 (64%) patients without acute abnormal findings on neuroimaging, 49 (36%) patients with these findings had a significantly higher mean CT lung severity score (9.9 versus 5.8, P < .001). These patients were more likely to present with ischemic stroke (40 [82%] versus 11 [13%], P < .0001) and were more likely to have either ground-glass opacities or consolidation (46 [94%] versus 73 [84%], P = .01) in the lungs. A threshold of the CT lung severity score of >8 was found to be 74% sensitive and 65% specific for acute abnormal findings on neuroimaging. The neuroimaging hallmarks of these patients were acute ischemic infarct (28%), intracranial hemorrhage (10%) including microhemorrhages (19%), and leukoencephalopathy with and/or without restricted diffusion (11%). The predominant CT chest findings were peripheral ground-glass opacities with or without consolidation. CONCLUSIONS: The CT lung disease severity score may be predictive of acute abnormalities on neuroimaging in patients with COVID-19 with neurologic manifestations. This can be used as a predictive tool in patient management to improve clinical outcome.

Temporal changes in brain volume and cognition in a randomized treatment trial of vascular dementia.

OBJECTIVE: To measure changes in brain and ischemic volume over time by magnetic resonance imaging (MRI) as part of a randomized treatment trial of vascular dementia. METHODS: Participants who met criteria for vascular dementia underwent comprehensive neurological and neuropsychological testing on entrance, during, and at completion of the 1-year study. For those centers who had easily available MRI, MRI of the brain was to be performed on entry and completion of the study. Image analysis was performed on all balanced and T2-weighted MR films to determine ventricular, sulcal, ischemic, and hemispheric brain volumes. RESULTS: Of the 105 patients who met the criteria for vascular dementia, 40 had a baseline MRI study that met protocol requirements and was of excellent image quality. The baseline ventricular volume in these 40 patients with high-quality MR correlated with most measures of cognitive and behavioral function, including the total Alzheimer's Disease Assessment Score (ADAS) (r = 0.51, P = .0024), as well as activities of daily living (r = 0.61, P = .0002). The baseline ischemic brain volume correlated well only with the gait and postural stability scale (r = 0.74, P = .009). Of the 40 participants, 25 had MRI studies at baseline and at completion of the study that were comparable and of excellent image quality. For these 25 patients, the mean ventricular volumes increased by 9% over the study year (P = .001) and the mean ischemic brain volume increased by 18% (P = .01). Temporal changes in the sulcal and nonischemic brain volume did not reach significance. None of the 14 clinical score measures changed significantly between baseline and completion of the study in these 25 patients. CONCLUSION: In summary, ventricular volume correlated well with cognitive measures in patients with vascular dementia and was a more sensitive marker for change during the study year than the clinical scales used in this study. This study also points out the practical limitations of brain imaging as a surrogate measure of clinical outcome in multicenter randomized treatment trials of brain disease.

Pathophysiology and treatment of enuresis in adults.

Monosymptomatic nocturnal enuresis (MNE) in children is partly the result of inadequate reduction in the rate of urine output at night. This nocturnal polyuria is due to the lack of a rise in the anti-diuretic hormone, arginine vasopressin (AVP), and can be reduced or eliminated by treatment with desmopressin at bedtime. Since there is a 1% incidence of MNE among adults, this study investigated the circadian pattern of solute and water balance in nine young adult enuretics before and during desmopressin therapy and compared the results with nine-age- and sex-matched, healthy controls. Before treatment, enuretics and controls had similar total fluid intake, urine output, urine osmolality, plasma osmolality, plasma total protein, mean arterial pressure and plasma AVP. The circadian pattern of fluid intake was also normal in enuretics. This abnormality could not be attributed to a deficiency of plasma AVP or an increase in solute excretion, since both variables were similar to controls. Rather, their nocturnal polyuria appeared to be due to a marked nocturnal reduction in renal sensitivity to the antidiuretic effect of vasopressin. In seven enuretics, restudied during treatment with desmopressin (10-30 micrograms o.d.), circadian urine output was normal and enuresis was absent. These results indicate that: (i) The circadian pattern of urine output in healthy adults is largely due to a nocturnal decrease in solute excretion rather than a rise in plasma AVP; (ii) The subset of adults with persistent MNE also have nocturnal polyuria as a result of insensitivity to the antidiuretic action of AVP; (iii) These defects can be corrected by treatment with desmopressin.

A novel mutation (R97C) in the neurophysin moiety of prepro-vasopressin-neurophysin II associated with autosomal-dominant neurohypophyseal diabetes insipidus.

Autosomal-dominant familial neurohypophyseal diabetes insipidus (adFNDI) is caused by heterozygous mutations in the gene encoding vasopressin-neurophysin II (AVP-NPII) on chromosome 20p13. We analyzed the AVP-NP II gene in a family with adFNDI by direct sequencing. A novel C to T transition (289C-->T in the cDNA, resulting in the substitution of Arg 97 by Cys (R97C) in the prepro-AVP-NPII precursor molecule) was identified in the gene region encoding neurophysin II in the index patient. This amino acid change is thought to result in the formation of an incorrectly folded hormone precursor, which may lead to chronic neurotoxicity and explain the dominant inheritance of the disease.

Volumetric measurement of multifocal brain lesions. Implications for treatment trials of vascular dementia and multiple sclerosis.

This pilot study examined the reproducibility of serial magnetic resonance (MR) measurements of brain, ventricular, sulcal, and lesion volumes in patients with ischemic brain disease using an image analysis protocol designed at the University of Cincinnati. Five patients with a clinical history of brain ischemia had two separate MR brain imaging studies using the standard clinical MR imaging protocol at the University of Cincinnati Medical Center. The MR images on both film and tape were digitized and then analyzed according to the standardized image analysis protocol. Based on tape data, variability in volume measurements between the two MR studies, as measured by the coefficient of variation, ranged from 1% for intracranial volume to 8% for ventricular volume. Variability based on film data was slightly greater, ranging from 2% for intracranial volume to 12% for lesion volume. As part of a multicenter treatment trial of vascular dementia, this method was then used to analyze MR films in 13 patients with vascular dementia who all had an MR study at baseline and at 1 year. The mean annual change in lesion volume was 4 +/- 5 cm3 (a 24% increase from the baseline lesion volume); in ventricular volume, 7 +/- 8 cm3 (a 10% increase from baseline); and in sulcal volume, 13 +/- 25 cm3 (a 5% increase from baseline). This method of image analysis, using MR film or tape-generated data, can provide reproducible serial measurements of brain, ventricular, sulcal, and ischemic lesion volumes. This method, if applied in randomized treatment trials of vascular dementia or multiple sclerosis, can be used to monitor disease progression and to evaluate the effectiveness of a given therapy.

Adaptive resetting of the volume control of vasopressin secretion during sustained hypovolemia.

To determine the effect of sustained hypovolemia on vasopressin secretion, we studied rats after 1-32 h of diuretic therapy. We found that an injection of furosemide (10 mg/kg) produced a transient marked increase in urine output, a moderate 7-10% reduction in blood volume, and a three- to fourfold rise in plasma vasopressin from 1.6 +/- 0.2 to 5.6 +/- 1.0 pmol/l. When the hypovolemia was maintained by repeated injections of the diuretic, plasma vasopressin remained elevated for > or = 8 h but returned almost to normal by 32 h, even though plasma electrolytes, blood pressure, hematocrit, and the other measures of hypovolemia were unchanged. At this time, pituitary vasopressin was undiminished, and plasma vasopressin rose normally or even supranormally when an acute hypovolemic or osmotic stimulus (intraperitoneal polyethylene glycol or hypertonic saline) was superimposed. However, the lines describing the relationship of log plasma vasopressin to plasma volume and plasma sodium in the rats treated with furosemide for 32 h lay to the left of the same relationships in the rats treated for 8 h or the sham-treated controls. We conclude that, in rats, the vasopressin response to sustained hypovolemia persists for > or = 8 h but is markedly diminished by 32 h. The decline in plasma vasopressin during this interval appears to be due to adaptive resetting of the volume control mechanism.

The effect of the nonselective opioid antagonist diprenorphine on vasopressin secretion in the rat.

Although endogenous opioids are thought to be involved in the regulation of vasopressin secretion, their precise role is unclear. We studied the effect of the potent nonselective opioid antagonist diprenorphine on the vasopressin response to osmotic (hypertonic saline, ip), hypovolemic (polyethylene glycol, ip), and hypotensive (sodium nitroprusside, sc) stimuli in male rats. We found that diprenorphine sc produced a time- and dose-dependent inhibition of the plasma vasopressin response to the hypovolemic stimulus. This inhibition was greatest 30 min after injection of the drug, but lasted for at least 4 h, was evident at doses as low as 0.0022 mumol/kg, and reached a maximum of about 85% of the stimulated control at a dose of 2.2 mumol/kg. Diprenorphine also inhibited the vasopressin response to an osmotic or a hypotensive stimulus, but the effect was less complete (approximately 50%), required 100-fold higher doses of the drug, and appeared to be bimodal. The potent kappa 1-selective opioid agonist U-50,488H also suppressed the vasopressin response to these stimuli, but the effect was not selective for hypovolemia, and the doses required (0.135-13.5 mumol/kg) were about 10- to 100-fold higher than those of diprenorphine. We postulate, therefore, that diprenorphine potently and preferentially inhibits the vasopressin response to an acute hypovolemic stimulus by antagonizing the effect of some endogenous opioidergic system critical in the volume control system.

The effect of selective opioid antagonists on vasopressin secretion in the rat.

We have shown previously that the nonselective opioid antagonist diprenorphine inhibits the vasopressin response to an acute hypovolemic stimulus in rats. To elucidate the type of endogenous opioid receptor at which this inhibition occurs, we investigated whether more selective antagonists, administered alone or in combination with diprenorphine, also inhibited the vasopressin response to hypovolemia induced by ip injection of polyethylene glycol. We found that the rise in plasma vasopressin was inhibited by the kappa-antagonist Mr 2266 BS at doses 30- to 300-fold higher than those of diprenorphine. Over the same dose range (0.003-100 mumol/kg), the kappa 1-selective antagonist norbinaltorphimine and the mu-selective antagonist naloxone had no effect or enhanced the vasopressin response, whereas the delta-antagonist ICI 154,129 had no effect. By augmenting the vasopressin response to hypovolemia, higher doses of naloxone or nor-binaltorphimine offset the inhibitory effect of concurrently administered diprenorphine. Mr 2266 BS did not facilitate, inhibit, or offset the action of diprenorphine. The results support the hypothesis that the inhibition of vasopressin by diprenorphine is due to antagonism of an opioid receptor and suggest that it is one of the recently discovered kappa-subtypes. They also suggest that the vasopressin response to acute hypovolemia is normally restrained by simultaneous activation of a distinct inhibitory pathway that is blocked by kappa 1- or mu-antagonists.

Opioid antagonist diprenorphine microinjected into parabrachial nucleus selectively inhibits vasopressin response to hypovolemic stimuli in the rat.

Subcutaneous injection of the potent, nonselective opioid antagonist diprenorphine inhibits the vasopressin response to acute hypovolemia. To determine if this inhibition is due to antagonism of opioid receptors in brain pathways that mediate volume control, we determined the vasopressin response to different stimuli when diprenorphine or other opiates were injected into the cerebral ventricles, the nucleus tractus solitarius (NTS), or the lateral parabrachial nucleus (PBN) of rats. We found that the vasopressin response to hypovolemia was inhibited by injection of diprenorphine into the cerebral ventricles at a dose too low to be effective when given subcutaneously. This response also was inhibited when a 20-fold lower dose of diprenorphine was injected into the PBN but not when it was injected into the NTS. The inhibitory effect of diprenorphine in the PBN was not attributable to a decrease in osmotic or hypovolemic stimulation and did not occur with osmotic or hypotensive stimuli. Injecting the PBN with equimolar doses of the mu antagonist naloxone, the delta antagonist ICI-154,129 or the kappa-1 agonist U-50,488H had no effect on basal or volume-stimulated vasopressin. We conclude that the inhibition of vasopressin by diprenorphine is due partially to action at a novel class of opioid receptors that transmit volume stimuli through the PBN.

Familial neurohypophyseal diabetes insipidus associated with a signal peptide mutation.

We studied the pathophysiology, natural history, and genetic basis of familial neurohypophyseal diabetes insipidus (FNDI) in a caucasian kindred. Twelve members had polyuria and a deficiency of plasma vasopressin (AVP), which progressed in severity over time. Another had normal urine volumes and plasma AVP when first tested at age 3 yr, but developed severe FNDI a year later. For unknown reasons, one man had a normal urine volume despite severe AVP deficiency and a history of polyuria in the past. When the AVP-neurophysin-II gene was amplified and sequenced, exon 2/3 was normal, but 7 of 12 clones of exon 1 contained a base substitution (G-->A) predicting a substitution of threonine for alanine at the -1 position of the signal peptide. Restriction analysis found the mutation in all 14 affected members, but in none of the 41 controls or 19 adult members with normal urine volumes and plasma or urinary AVP (lod score = 5.7). The mutation was also found in 2 infants in whom AVP was normal when tested at 6 and 9 months of age. We hypothesize that a mutation in exon 1 of the AVP-neurophysin-II gene causes FNDI in this kindred by making an abnormally processed precursor that gradually destroys vasopressinergic neurons.

Innovative desktop learning tools. Implications for rural hospitals and physicians.

Innovative methods of providing workplace education for health care professionals may be a key to the survival of rural hospitals in America. Such methods must overcome time, distance, cost and organizational constraints, and take into account the structure of the learning experience. The Texas Hospital Education and Research Foundation has recently been involved in two programs that tested new approaches to worker education using distance-learning strategies. The projects--resource sharing among rural directors of nursing and training for cancer tumor registrars--used computer-conferencing technology. A new model using existing satellite, audio-conferencing, and computer-based instruction augmented by computer conferencing is proposed. The Computer-Related Assisted Distance Learning Enhancement (CRADLE) model integrates existing technologies to provide education to health care workers at their desktop. The Cancer Learning Center (CLC) tested peer collaboration, the primary component of the model. The ultimate goal is to have the system available to all tumor registrars in Texas, and to secure funding to implement rural nursing and rural high-school health occupations education projects. Current projects from set-up through results are presented.

Midline anterior atlas clefts: CT findings.

Anterior atlas clefts (AACs) are rare developmental variants that may mimic fractures. Due to the potential severe implications of craniocervical junction trauma, expeditious differentiation between a Jefferson burst fracture and a congenital cleft is essential in trauma patients. Three cases of AAC are presented. Two cases demonstrated incidental AACs; the third case was associated with a Jefferson burst injury. Computed tomography is most helpful in evaluating the integrity of the atlas; however, plain radiography or pluridirectional tomography are best for evaluating displacement of the lateral masses of C1 in relation to C2.

Emergency care. Texas hospitals to the rescue.

An average of 17 Texans die every day as a result of accidental injuries. Our ability to respond to trauma in Texas will be a high priority issue in the upcoming Legislative session. In the meantime, metropolitan areas and remote rural locations across Texas have had to come up with ways to handle what is often a trauma crisis. Efforts are also underway to reduce the number of accidents and injuries in the first place. This month, HealthTexas takes a look at these trauma issues.

Lumbar disc disease and stenosis.

In recent years MR has been the major advancement in the imaging of lumbar disc disease. Its advantages include multiplanar imaging, excellent resolution, and absence of ionizing radiation. Although CT remains an efficient and accurate method of evaluating the spine, we currently recommend MR imaging as the best initial examination. Myelography with follow-up CT scans should be reserved for specific patients in whom additional information is needed after MR images or CT scans.