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Sickle cell disease (SCD) is the most common genetic blood disorder, characterized by red cell hemolysis, anemia, and corresponding increased compensatory cerebral blood flow (CBF). SCD patients are at high risk for cerebral infarcts and CBF quantification is likely critical to assess infarct risk. Infarcts primarily localize to white matter (WM), yet arterial spin labeling (ASL) MRI, the most common non-invasive CBF approach, has poor WM CBF sensitivity owing to low WM CBF and long WM bolus arrival time (BAT). We hypothesize that anemia, and associated cerebral hyperemia, in SCD leads to improved WM detection with ASL. We performed 3-Tesla multi-delay pulsed ASL in SCD (n = 35; age = 30.5 ± 8.3 years) and control (n = 15; age = 28.7 ± 4.5 years) participants and applied t-tests at each inversion time within different flow territories, and determined which regions were significantly above noise floor (criteria: one-sided p < 0.05). Total WM CBF-weighted signal was primarily detectable outside of borderzone regions in SCD (CBF = 17.7 [range = 12.9-25.0] mL/100 g/min), but was largely unphysiological in control (CBF = 8.1 [range = 7.6-9.9)] mL/100 g/min) participants. WM BAT was reduced in SCD versus control participants (ΔBAT = 37 [range = 46-70] ms) and BAT directly correlated with hematocrit (Spearman's-ρ = 0.62; p < 0.001). Findings support the feasibility of WM CBF quantification using ASL in SCD participants for appropriately parameterized protocols., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: MJD receives research related support from the National Institutes of Health (NINDS, NCI, NIA, NCCIH, NINR, and NHLBI), Philips Healthcare, Pfizer Inc and is a paid consultant for Graphite Bio, Pfizer Inc, Global Blood Therapeutics, Woolsey Pharmaceuticals, Alterity Pharmaceuticals, and LymphaTouch. He is a paid advisory board member for Pfizer Inc, Novartis and bluebird bio and is the CEO of Biosight Inc which operates as a clinical research organization. These agreements have been approved by Vanderbilt University Medical Center in accordance with its conflict of interest policy.

Background: Peri-sinus structures such as arachnoid granulations (AG) and the parasagittal dural (PSD) space have gained much recent attention as sites of cerebral spinal fluid (CSF) egress and neuroimmune surveillance. Neurofluid circulation dysfunction may manifest as morphological changes in these structures, however, automated quantification of these structures is not possible and rather characterization often requires exogenous contrast agents and manual delineation., Methods: We propose a deep learning architecture to automatically delineate the peri-sinus space (e.g., PSD and intravenous AG structures) using two cascaded 3D fully convolutional neural networks applied to submillimeter 3D T 2 -weighted non-contrasted MRI images, which can be routinely acquired on all major MRI scanner vendors. The method was evaluated through comparison with gold-standard manual tracing from a neuroradiologist (n = 80; age range = 11-83 years) and subsequently applied in healthy participants (n = 1,872; age range = 5-100 years), using data from the Human Connectome Project, to provide exemplar metrics across the lifespan. Dice-Sørensen and a generalized linear model was used to assess PSD and AG changes across the human lifespan using quadratic restricted splines, incorporating age and sex as covariates., Results: Findings demonstrate that the PSD and AG volumes can be segmented using T 2 -weighted MRI with a Dice-Sørensen coefficient and accuracy of 80.7 and 74.6, respectively. Across the lifespan, we observed that total PSD volume increases with age with a linear interaction of gender and age equal to 0.9 cm 3 per year (p < 0.001). Similar trends were observed in the frontal and parietal, but not occipital, PSD. An increase in AG volume was observed in the third to sixth decades of life, with a linear effect of age equal to 0.64 mm 3 per year (p < 0.001) for total AG volume and 0.54 mm 3 (p < 0.001) for maximum AG volume., Conclusions: A tool that can be applied to quantify PSD and AG volumes from commonly acquired T 2 -weighted MRI scans is reported and exemplar volumetric ranges of these structures are provided, which should provide an exemplar for studies of neurofluid circulation dysfunction. Software and training data are made freely available online ( https://github.com/hettk/spesis )., (© 2024. The Author(s).)

Impulsive-compulsive behaviours manifest in a substantial proportion of subjects with Parkinson's disease. Reduced ventral striatum dopamine receptor availability, and increased dopamine release is noted in patients with these symptoms. Prior studies of impulsivity suggest that midbrain D2 autoreceptors regulate striatal dopamine release in a feedback inhibitory manner, and in healthy populations, greater impulsivity is linked to poor proficiency of this inhibition. This has not been assessed in a Parkinson's disease population. Here, we applied 18F-fallypride PET studies to assess striatal and extrastriatal D2-like receptor uptake in a placebo-controlled oral dextroamphetamine sequence. We hypothesized that Parkinson's disease patients with impulsive-compulsive behaviours would have greater ventral striatal dopaminergic response to dextroamphetamine, and that an inability to attenuate ventral striatal dopamine release via midbrain D2 autoreceptors would underlie this response. Twenty patients with Parkinson's disease (mean age = 64.1 ± 5.8 years) both with (n = 10) and without (n = 10) impulsive-compulsive behaviours, participated in a single-blind dextroamphetamine challenge (oral; 0.43 mg/kg) in an OFF dopamine state. All completed PET imaging with 18F-fallypride, a high-affinity D2-like receptor ligand, in the placebo and dextroamphetamine state. Both voxelwise and region of interest analyses revealed dextroamphetamine-induced endogenous dopamine release localized to the ventral striatum, and the caudal-medial orbitofrontal cortex. The endogenous dopamine release observed in the ventral striatum correlated positively with patient-reported participation in reward-based behaviours, as quantified by the self-reported Questionnaire for Impulsivity in Parkinson's disease Rating Scale. In participants without impulsive-compulsive behaviours, baseline midbrain D2 receptor availability negatively correlated with ventral striatal dopamine release; however, this relationship was absent in those with impulsive-compulsive behaviours. These findings emphasize that reward-based behaviours in Parkinson's disease are regulated by ventral striatal dopamine release, and suggest that loss of inhibitory feedback from midbrain autoreceptors may underlie the manifestation of impulsive-compulsive behaviours., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Impulsivity is inherent to behavioral disorders such as substance abuse and binge eating. While the role of dopamine in impulse behavior is well established, γ-aminobutyric acid (GABA) therapies have promise for the treatment of maladaptive behaviors. In Parkinson disease (PD), dopaminergic therapies can result in the development of impulsive and compulsive behaviors, and this clinical syndrome shares similar pathophysiology to that seen in addiction, substance abuse, and binge-eating disorders. We hypothesized that impulsive PD patients have a reduced thalamic GABAergic response to dopamine therapy. To test this hypothesis, we employed GABA magnetic resonance spectroscopy, D2-like receptor PET imaging, and clinical and quantitative measures of impulsivity in PD patients (n = 33), before and after dopamine agonist administration. We find a blunted thalamic GABA response to dopamine agonists in patients with elevated impulsivity (p = 0.027). These results emphasize how dopamine treatment differentially augments thalamic GABA concentrations, which may modify behavioral impulsivity., (© 2022. The Author(s).)

Voxel-based morphometry is an established technique to study focal structural brain differences in neurologic disease. More recently, texture-based analysis methods have enabled a pattern-based assessment of group differences, at the patch level rather than at the voxel level, allowing a more sensitive localization of structural differences between patient populations. In this study, we propose a texture-based approach to identify structural differences between the cerebellum of patients with Parkinson's disease (n = 280) and essential tremor (n = 109). We analyzed anatomical differences of the cerebellum among patients using two features: T1-weighted MRI intensity, and a texture-based similarity feature. Our results show anatomical differences between groups that are localized to the inferior part of the cerebellar cortex. Both the T1-weighted intensity and texture showed differences in lobules VIII and IX, vermis VIII and IX, and middle peduncle, but the texture analysis revealed additional differences in the dentate nucleus, lobules VI and VII, vermis VI and VII. This comparison emphasizes how T1-weighted intensity and texture-based methods can provide a complementary anatomical structure analysis. While texture-based similarity shows high sensitivity for gray matter differences, T1-weighted intensity shows sensitivity for the detection of white matter differences., (© 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Objective: To describe a case of mannitol overdose associated with acute kidney injury (AKI), hypertonic hyponatremia, and neurologic abnormalities in a dog., Case Summary: A 10-year-old intact male Shiba Inu dog was referred to the emergency service of a veterinary teaching hospital for inappetence and acute onset of seizures. The dog had received 2 IV boluses of 3 g/kg of mannitol in less than 24 hours for a glaucoma crisis. Twelve hours after the second injection, the dog became inappetant and developed 2 generalized seizures. Seizure activity was treated with diazepam (0.5 mg/kg IV). Serum biochemistry profile showed severe hyponatremia and hypochloremia, mild hypokalemia, marked increased creatinine (381 µmol/L [44-133 µmol/L]) and moderately increased BUN (13.8 mmol/L [1.6-10.9 mmol/L]). Urinalysis revealed a urine specific gravity of 1.018, glucosuria, proteinuria, pigmenturia and the presence of vacuolized tubular epithelial cells. A presumptive diagnosis of mannitol intoxication was made based on the high dose of mannitol, severe hyponatremia, neurological abnormalities suggestive of intracranial disease, AKI, and urine cytology. Initial calculated plasma osmolality was 263.4 mOsm/kg and measured plasma osmolality was 332 mOsm/kg with an osmolal gap of 68.6 mOsm/kg, confirming the presence of an unmeasured solute attributed to mannitol. Treatment consisted of fluid therapy and supportive care. On day 3, osmolal gap had resolved and serum creatinine concentration returned to normal within 12 days., New or Unique Information Provided: Mannitol intoxication has been reported in human medicine. This case report is, to our knowledge, the first to describe AKI, hypertonic hyponatremia, and neurological abnormalities secondary to mannitol overdose in a dog., (© Veterinary Emergency and Critical Care Society 2019.)

A domestic shorthair cat was referred for progressive muscle weakness and dyspnoea. The cat had a 2-month history of severe weight loss, small intestinal diarrhoea, polyphagia and polyuria/polydipsia. Biochemical analysis and venous blood gas evaluation revealed severe hypokalaemia [1.7 mmol/l; reference interval (RI): 3.5-5.1 mmol/l] and hypoventilation (partial pressure of carbon dioxide = 68 mmHg; RI: 34-38 mmHg). Aggressive potassium supplementation was initiated. The cat was manually ventilated until serum potassium increased to 3 mmol/l. A diagnosis of exocrine pancreatic insufficiency (EPI) was made based on clinical signs and serum feline trypsin-like immunoreactivity (0.1 μg/l; RI: 12-82 μg/l). Medical management of the EPI resulted in clinical recovery.

Background: The buccal mucosal bleeding time (BMBT) evaluates primary hemostasis in vivo. Three different-sized lancet devices designed for people, Adult (A), Junior (J), and Newborn (N), can be used to perform the BMBT in dogs., Objectives: The aim was to compare BMBT using 3 different-sized human lancet devices in dogs with varying platelet counts and hematocrits., Methods: The BMBT was measured in 46 client-owned dogs (2 healthy, 44 suffering from various disorders) with varying platelet (Plt) counts and hematocrits, using the 3 devices successively in each dog, in a randomly determined order, over a 10- to 30-minute period. Statistical analysis (ANOVA, Mann-Whitney U-test) was performed using commercial software., Results: BMBTs were significantly different between devices (P < .00001), and shorter with devices N and J compared with device A (P < .01). The BMBT was prolonged (> 210 s) in 10 dogs with device A and in 7 dogs each with devices J and N, respectively. Sixteen dogs had a Plt count < 200 × 10(9) /L (Reference interval 200-500 × 10(9) /L). Nine of these dogs had prolonged BMBT with device A, and 6 dogs with device J and device N, respectively. BMBT was longer in thrombocytopenic dogs with devices A and J (P < .016). Anemia without thrombocytopenia did not affect BMBT with any device., Conclusions: The BMBT is influenced by the size of the used device, with A resulting in the longest BMBT. Therefore, the type of device used to obtain the BMBT has to be specified for standardized results., (© 2013 American Society for Veterinary Clinical Pathology.)

Objective: To describe a case of cerebral babesiosis and acute respiratory distress syndrome (ARDS) in a dog., Case Summary: A 5-year-old male neutered Scottish Terrier was referred to the emergency department of the Ecole Nationale Vétérinaire de Toulouse for evaluation of progressive dyspnea and clinical signs suggestive of central neurological disease. Thoracic radiographs showed a diffuse and heavy interstitial/alveolar lung pattern. Babesiosis was diagnosed based on blood smear evaluation. The dog died of cardiopulmonary arrest 6 hours after presentation. Cerebral babesiosis and ARDS were confirmed at necropsy. Major pathological findings included erythrocyte aggregation in the lungs, liver, and brain., New or Unique Information Provided: This case report describes an unusual clinical presentation of Babesia canis canis infection, the most common species associated with babesiosis in Europe. In addition, this is to our knowledge the first case of Babesia-associated ARDS confirmed by histopathology in a dog., (© Veterinary Emergency and Critical Care Society 2013.)

Rationale: Dopamine systems vary through development in a manner that can impact drugs acting on those systems. Dietary factors can also impact the effects of drugs acting on dopamine systems., Objectives: This study examined whether eating high fat chow alters locomotor effects of cocaine (1-56 mg/kg) in adolescent and adult female rats., Methods: Cocaine was studied in rats (n = 6/group) with free access to standard (5.7% fat) or high fat (34.3%) chow or restricted access to high fat chow (body weight matched to rats eating standard chow)., Results: After 1 week of eating high fat chow (free or restricted access), sensitivity to cocaine was significantly increased in adolescent and adult rats, compared with rats eating standard chow. Sensitivity to cocaine was also increased in adolescent rats with restricted, but not free, access to high fat chow for 4 weeks. When adolescent and adult rats that previously ate high fat chow ate standard chow, sensitivity to cocaine returned to normal. In adolescent and adult female rats eating high fat chow, but not those eating standard chow, sensitivity to cocaine increased progressively over once weekly tests with cocaine (i.e., sensitization) in a manner that was not statistically different between adolescents and adults., Conclusions: These results show that eating high fat chow alters sensitivity of female rats to acutely administered cocaine and also facilitates the development of sensitization to cocaine. That the type of food consumed can increase drug effects might have relevance to vulnerability to abuse cocaine in the female population.

Central venous pressure (CVP), an estimate of right atrial pressure, has been used to assess cardiac preload and volume status in critically ill patients, assist in the diagnosis of right-sided heart failure, and guide fluid resuscitation. It is determined by the interaction between cardiac function and venous return. CVP measurements are relatively easy to obtain; however, because of the complex relationship between CVP, cardiac output, and the vascular system, they may be difficult to interpret. This article reviews the physiologic principles of CVP, indications for its use, technical aspects and pitfalls of CVP measurements, and interpretation of the information obtained.

Objective: To review the topic of ventilator waveforms analysis with emphasis on interpretation of ventilator waveforms and their use in the management and monitoring of mechanically ventilated small animal patients., Data Sources: Human clinical studies, scientific reviews, and textbooks, as well as veterinary textbooks and clinical examples of ventilator waveforms in mechanically ventilated dogs., Summary: Ventilator waveforms are graphic representations of data collected from the ventilator and reflect patient-ventilator interactions. The 4 parameters pressure, volume, flow, and time are most descriptive of mechanical ventilation. Typically, 3 different graphs, also referred to as scalars, consisting of pressure versus time, volume versus time, and flow versus time, with time always plotted on the x-axis, are used. Changes in the ventilator settings as well as in the characteristics of the lungs such as airway resistance (R(aw)) and respiratory system compliance (C(rs)) can be recognized from specific variations in the waveforms. Flow-volume and pressure-volume loops provide additional information about changes in lung function. Patient-ventilator dyssynchrony is a common problem during mechanical ventilation and can lead to patient discomfort and an increased work of breathing. Ventilator waveforms are helpful to identify dyssynchrony, which can be divided into trigger, flow, cycle, and expiratory dyssynchrony. Ventilator waveforms allow the clinician to assess changes in respiratory mechanics, and can be useful in monitoring the progression of disease pathology and response to therapy. Adjustments in ventilator settings based on proper analysis and interpretation of these waveforms can help the clinician to optimize ventilation therapy., Conclusions: Ventilator waveforms are graphic representations of patient-ventilator interactions. Proper interpretation of ventilator waveforms affords the critical care clinician a better understanding of the patient's respiratory function, response to therapy, and causes for patient-ventilator dyssynchrony. Ventilator waveform interpretation is an important tool in the assessment and management of mechanically ventilated small animal patients., (© Veterinary Emergency and Critical Care Society 2011.)

Lung lobe torsion is a rare pulmonary disorder in small animals and in humans. Torsion occurs when the lung lobe rotates around the bronchus and vascular supply and remains in that position. Lung lobe torsion is a life-threatening condition. The patient may present in an acute, fulminant respiratory crisis; however, more subtle clinical signs have also been reported. Lung lobe torsion may be secondary to an underlying pathology or spontaneous and idiopathic. Surgical resection of the affected lung lobe is the treatment of choice. The prognosis depends on the underlying cause. This article reviews the incidence, pathophysiology, clinical signs, diagnostic approach, and treatment of lung lobe torsion in dogs and cats.

Xylitol, a sugar substitute used in sugar-free gum, oral care products, and baked goods, is gaining popularity in the United States. Xylitol consumption is considered harmless to people but is known to cause life-threatening toxicoses in dogs. Dogs that ingest doses of >0.1 g/kg of xylitol are at risk for developing hypoglycemia, while dogs that ingest >0.5 g/kg may develop acute liver failure. Treatment includes dextrose supplementation for hypoglycemia and aggressive monitoring, treatment, and supportive care for dogs experiencing hepatotoxicosis. The prognosis for dogs with uncomplicated hypoglycemia is good, whereas the prognosis for dogs that develop severe hepatotoxicosis is guarded to poor.

The plasma concentrations of isosorbide dinitrate (ISDN) and its two pharmacologically active metabolites isosorbide 2-mononitrate (IS-2-MN) and isosorbide 5-mononitrate (IS-5-MN) were determined after oral administration of 20 mg ISDN and 20 mg of each of the mononitrates. The mean concentration-time curve of ISDN showed a peak of 51.6 ng/ml 15 min after drug intake, and declined bi-exponentially with a terminal half-life of 36.5 min. The mean concentrations of the simultaneously measured metabolic products IS-2-MN and IS-5-MN reached a maximum of 40.5 ng/ml and 144.4 ng/ml, respectively. In contrast, after the direct ingestion of isosorbide mononitrates, peaks of 409.1 ng/ml (IS-2-MN) and 483.2 ng/ml (IS-5-MN) were observed in the corresponding mean curves. Mean half-lives of 1.72 h for IS-2-MN and 4.20 h for IS-5-MN were calculated. The mean apparent volumes of distribution were 44.5 l (IS-2-MN) and 34.4 l (IS-5-MN), suggesting that the isosorbide mononitrates are distributed throughout the whole body fluid. After ISDN administration, it was estimated that 3.0 mg IS-2-MN and 7.8 mg IS-5-MN reached the systemic circulation. This corresponds to 63% of the ISDN dose being converted to isosorbide mononitrates by metabolic processes.