Severity of myxomatous mitral valve disease in dogs may be predicted using neutrophil-to-lymphocyte and monocyte-to-lymphocyte ratio.

OBJECTIVE: To investigate the neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) in dogs with myxomatous mitral valve disease (MMVD). ANIMALS: 106 dogs with MMVD and 22 healthy dogs were included in the study. PROCEDURES: CBC data were obtained retrospectively, and NLR, MLR, and PLR were compared between dogs with MMVD and healthy dogs. The ratios were also analyzed according to MMVD severity. RESULTS: NLR and MLR were significantly higher in dogs with MMVD C and D (NLR of 4.99 [3.69-7.27]; MLR of 0.56 [0.36-0.74]) than in healthy dogs (NLR: 3.05 [1.82-3.37], P < .001; MLR: 0.21 [0.14-0.32], P < .001), MMVD stage B1 (NLR: 3.15 [2.15-3.86], P < .001; MLR: 0.26 [0.20-0.36], P < .001), and MMVD stage B2 dogs (NLR: 3.22 [2.45-3.85], P < .001; MLR: 0.30 [0.19-0.37], P < .001). The area under the receiver operating characteristic curves of the NLR and MLR to distinguish dogs with MMVD C and D from those with MMVD B were 0.84 and 0.89, respectively. The optimal cutoff value for NLR was 4.296 (sensitivity, 68%; specificity, 83.95%), and the MLR value was 0.322 (sensitivity, 96%; specificity, 66.67%). NLR and MLR were significantly decreased after treatment in dogs with congestive heart failure (CHF). CLINICAL RELEVANCE: NLR and MLR can be used as adjunctive indicators of CHF in dogs.

Investigation of canine caudal articular process dysplasia of thoracic vertebrae using computed tomography: Prevalence and characteristics.

Caudal articular process (CAP) dysplasia is a congenital vertebral malformation that results from the failure of ossification center of articular process located in vertebrae, which includes aplasia or hypoplasia. In previous studies, it was reported to be common in small and chondrodystrophic dogs however, investigated in limited breeds. So we aimed to confirm the prevalence and the characteristics of CAP dysplasia in various breeds, and also to investigate the association of CAP dysplasia and spinal cord myelopathy in neurologically abnormal dogs. In this multicenter, retrospective study, the clinical records and thoracic vertebral column computed tomographic (CT) images of 717 dogs between February 2016 and August 2021 were included and 119 dogs which also underwent magnetic resonance imaging (MRI) examination were evaluated. Overall, 337 of 717 dogs (47.0%) had at least one thoracic CAP dysplasia and the prevalence of CAP dysplasia was significantly higher in dogs with a lower body weight (P < 0.0001). A total of 66.4% of toy breeds, 39.0% of small breeds, 20.2% of medium breeds, and 6.0% of large breeds were affected by at least one CAP dysplasia. The most affected vertebra was T4 in toy (48.1%) and small breeds (20.8%), and T5 in medium (20.8%) and large breeds (5.0%). In all groups, prevalence of CAP dysplasia between T1 and T9 was higher than post-diaphragmatic vertebrae (T10-T13). Fifty nine of 119 dogs which underwent both CT and MRI examination had symptoms of spinal cord myelopathy of T3-L3 and twenty-five of 59 dogs (42.3%) had at least one thoracic CAP dysplasia. In that 25 neurologically abnormal dogs, 41 sites of intervertebral disc disease (IVDD) were detected. However, only one dog had both CAP dysplasia and herniated disc at the same level. Also, CAP dysplasia associated non-compressive spinal myelopathy at the same level was found in the other dog. Association CAP dysplasia with spinal myelopathy is speculated but is not confirmed by this study.

18F-fluorodeoxyglucose positron emission tomography findings of peripheral nerve sheath tumour of the nasal cavity in a dog.

An 8-year-old Miniature Poodle presented with chronic sneezing and unilateral epistaxis. A left-sided intranasal mass was identified on computed tomography. 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) was performed to evaluate the metabolic activity of the mass. The intranasal mass showed mildly increased 18F-FDG uptake. The maximal and mean standardized uptake values (SUVs) of the mass were 3.4 and 2.6, respectively. The maximal SUV of the mass/mean SUV of the normal liver was 2.5. The 7-cm soft, pink mass was easily removed through rhinoscopy, with subsequent dramatic improvement in clinical signs. Histopathological and immunohistochemical analyses determined that the mass was an intermediate-grade malignant peripheral nerve sheath tumour (PNST). This is the first report of 18F-FDG PET findings in a PNST in dogs.

Can CT texture analysis parameters be used as imaging biomarkers for prediction of malignancy in canine splenic tumors?

Splenic hemangiosarcoma has morphological similarities to benign nodular hyperplasia. Computed tomography (CT) texture analysis can analyze the texture of images that the naive human eye cannot detect. Recently, there have been attempts to incorporate CT texture analysis with artificial intelligence in human medicine. This retrospective, analytical design study aimed to assess the feasibility of CT texture analysis in splenic masses and investigate predictive biomarkers of splenic hemangiosarcoma in dogs. Parameters for dogs with hemangiosarcoma and nodular hyperplasia were compared, and an independent parameter that could differentiate between them was selected. Discriminant analysis was performed to assess the ability to discriminate the two splenic masses and compare the relative importance of the parameters. A total of 23 dogs were sampled, including 16 splenic nodular hyperplasia and seven hemangiosarcoma. In each dog, total 38 radiomic parameters were extracted from first-, second-, and higher-order matrices. Thirteen parameters had significant differences between hemangiosarcoma and nodular hyperplasia. Skewness in the first-order matrix and GLRLM_LGRE and GLZLM_ZLNU in the second, higher-order matrix were determined as independent parameters. A discriminant equation consisting of skewness, GLZLM_LGZE, and GLZLM_ZLNU was derived, and the cross-validation verification result showed an accuracy of 95.7%. Skewness was the most influential parameter for the discrimination of the two masses. The study results supported using CT texture analysis to help differentiate hemangiosarcoma from nodular hyperplasia in dogs. This new diagnostic approach can be used for developing future machine learning-based texture analysis tools.

Development of three-dimensional canine hepatic tumor model based on computed tomographic angiography for simulation of transarterial embolization.

Introduction: Transarterial embolization (TAE) is one of the treatment options for liver masses that are not suitable for surgery and they have been applied in veterinary medicine for about 20 years, but surgical resection is considered as the first treatment option, and only a few case reports and articles about TAE in dogs have been published. Although understanding of vascular anatomy for the procedure is important, previous studies lack of the information about hepatic artery anatomy in small and toy-breed dogs. Due to the introduction of 3D print in veterinary medicine, it is now possible to make 3D models for preoperative planning. The purpose of this study is to understand the hepatic arterial vascular structure of various sizes and breeds of dogs, and to develop 3D-printed canine artery models with and without hepatic tumors to simulate TAE procedure. Methods: CT images of a total of 84 dogs with normal hepatic arteries were analyzed, and the mean value and standard deviation of body weight, celiac artery size, and hepatic artery size were 6.47 ± 4.44 kg, 3.28 ± 0.77 mm, and 2.14 ± 0.43 mm, respectively. Results: It was established that type 2-2-1, which has two separate hepatic branches-the right medial and left branch and the right lateral branch that runs to the right lateral lobe and caudate process-is the most prevalent of the hepatic artery branch types, as it was in the previous study. The review of 65 CT images of dogs with hepatic tumors showed that 44.6% (29/65) had multifocal lesions in multiple lobes, for which TAE can be recommended. Discussion: Based on the result, a 3D model of the normal canine hepatic artery and the hepatic tumor was made using one representative case from each group, and despite the models having some limitations in reflecting the exact tactile and velocity of blood vessels, TAE procedure was successfully simulated using both models.

Case Report: 18F-Fluoro-L-Phenylalanine Positron Emission Tomography Findings and Immunoreactivity for L-Type Amino Acid Transporter 1 in a Dog With Meningioma.

A 12-year-old intact female Miniature Pinscher dog weighing 5.4 kg presented with a history of seizures. On neurological examination, postural reactions were decreased in the left-sided limbs, and menace responses were bilaterally absent. Magnetic resonance imaging (MRI) of the brain was performed, and a solitary amorphous mass (2.7 × 1.9 × 2.2 cm) was observed on the right side of the frontal lobe. Based on the signalment, clinical signs, and MRI findings, a brain tumor was tentatively diagnosed, and meningioma was suspected. The dog was treated with hydroxyurea, prednisolone, and other antiepileptic drugs. One week after the treatment began, postural reactions returned to normal, and the menace response improved. At 119 days after treatment, 18F-fluoro-L-phenylalanine (18F-FDOPA) positron emission tomography (PET) was performed. Marked 18F-FDOPA uptake was observed in the lesion. The mean and maximal standardized uptake values of the lesion were 2.61 and 3.72, respectively, and the tumor-to-normal tissue ratio was 1.95. At 355 days after the initial treatment, a second MRI scan was performed and the tumor size had increased to 3.5 × 2.8 × 2.9 cm. The dog died 443 days after the initial treatment and was definitively diagnosed with grade 1 meningioma by histopathological examination. Immunohistochemical staining for Ki67 and L-type amino acid transporter 1 was positive and negative for p53, respectively. The labeling index of Ki67 was 2.4%. This is the first case to demonstrate 18F-FDOPA PET findings in a clinical case of a dog histologically diagnosed with a meningioma.

18F-FDG PET/CT image findings of a dog with adrenocortical carcinoma.

BACKGROUND: In human medicine, 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) has been used to differentiate between benign and malignant adrenal tumors and to identify metastases. However, canine adrenocortical carcinomas identified by 18F-FDG PET/computed tomography (CT) have not been reported. CASE PRESENTATION: A 13-year-old, castrated male, Cocker Spaniel dog with severe systolic hypertension exhibited an adrenal mass approximately 3.6 cm in diameter on ultrasonography. There was no evidence of pulmonary metastasis or vascular invasion on thoracic radiography and abdominal ultrasonography, respectively. 18F-FDG PET/CT was performed to identify the characteristics of the adrenal mass and the state of metastasis. One hour after injection of 5.46 MBq/kg 18F-FDG intravenously, the peripheral region of the adrenal mass visually revealed an increased 18F-FDG uptake, which was higher than that of the liver, and the central region of the mass exhibited necrosis. The maximal standardized uptake value (SUV) of the adrenal mass was 3.24; and relative SUV, calculated by dividing the maximal SUV of the adrenal tumor by the mean SUV of the normal liver, was 5.23. Adrenocortical carcinoma was tentatively diagnosed and surgical adrenalectomy was performed. Histopathologic examination of the resected adrenal mass revealed the characteristics of an adrenocortical carcinoma. After adrenalectomy, systolic blood pressure reduced to below 150 mmHg without any medication. CONCLUSION: This is the first case report of 18F-FDG PET/CT findings in a dog with suspected adrenocortical carcinoma and may provide valuable diagnostic information for adrenocortical carcinoma in dogs.

Characteristics of 18F-FDG and 18F-FDOPA PET in an 8-year-old neutered male Yorkshire Terrier dog with glioma: long-term chemotherapy using hydroxyurea plus imatinib with prednisolone and immunoreactivity for PDGFR-ß and LAT1.

An 8-year-old neutered male Yorkshire Terrier dog presented with head pressing, vestibular ataxia, neck tenderness, and no oculocephalic reflex. A demarcated lesion in the pons was identified on MRI. The patient was tentatively diagnosed with a glioma and was treated with hydroxyurea plus imatinib and prednisolone. After 30 days of therapeutic treatment, the patient showed a clear improvement in neurological signs, which lasted for 1117 days. On day 569 after the initiation of treatment, 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) was performed with no significant findings on visual analysis. The average and maximal standardized uptake values (SUVs) were 1.92 and 2.29, respectively. The tumor-to-normal-tissue (T/N) ratio was 0.97. The first evidence of clinical deterioration was noticed on day 1147. On day 1155, 3,4-dihydroxy-6-[18F]-fluoro-l-phenylalanine (18F-FDOPA)-PET was performed. High uptake of 18F-FDOPA was observed in the intracranial lesion. The mean and maximal SUVs of the tumor were 1.59 and 2.29, respectively. The T/N ratio was 2.22. The patient was euthanized on day 1155 and histopathologic evaluations confirmed glioma (astrocytoma). This case shows that chemotherapy with hydroxyurea plus imatinib may be considered in the treatment of canine glioma. Furthermore, this is the first case describing the application of 18F-FDG and 18F-FDOPA in a dog with glioma.

CT and radiographic evaluation of bronchial collapsibility at forced expiration in asymptomatic brachycephalic dogs.

Bronchial collapse due to bronchomalacia is an important cause of chronic coughing in dogs. Radiographic and CT evidence of bronchial collapse has previously been reported in healthy Beagle dogs under forced expiration. However, published studies in brachycephalic dog breeds that are prone to bronchial collapse are currently lacking. In the present prospective analytical experimental study, CT and radiography were used to measure the bronchial diameter and collapsibility of each pulmonary bronchus during end-expiratory, 5 mL/kg forced-expiratory, and 10 mL/kg forced-expiratory phases in 17 asymptomatic brachycephalic dogs and six healthy Beagle dogs. Bronchial collapsibility was significantly greater during forced expiration, than that at the end of expiration in both groups (P < .001). Bronchial collapsibility measurements of the left lung lobes and the right cranial, middle, and accessory lobes were significantly higher in asymptomatic brachycephalic dogs than those in healthy Beagle dogs, during all expiratory phases (P < .05). The higher bronchial collapsibility of brachycephalic dogs was also supported using CT multiplanar reconstruction images and radiography. In conclusion, radiographic and CT measures of bronchial collapsibility in asymptomatic brachycephalic dogs are higher than measures in healthy Beagle dogs. Therefore, measures of bronchial collapse in brachycephalic dogs should not be evaluated using the same baseline measures as those used for healthy Beagle dogs.

Computed tomographic and radiographic bronchial collapse may be a normal characteristic of forced expiration in dogs.

Tracheobronchomalacia has been diagnosed using radiography or bronchoscopy to confirm bronchial changes in luminal diameter during the respiratory cycle. However, studies in healthy humans suggest that some degree of bronchial collapse may be observed during the normal respiratory cycle. In this analytical study, the luminal diameter of the bronchus to each of the six pulmonary lobes and the mean percentage of expiratory collapse from end inspiratory, end expiratory, and two forced expiratory phases (10 and 15 ml/kg) were determined via computed tomography (CT) and radiography in 22 healthy Beagle dogs. The bronchial collapsibility was significantly greater during the forced expiration than the end expiration (P < 0.001); the same results were observed in dorsal and sagittal CT images and radiographs (P < 0.001). Median collapsibility values associated with 15 ml/kg forced expiratory collapse determined via cross-sectional CT images were measured as 16.6-45.5% and differed according to the pulmonary lobe. Median collapsibilities on radiography with 15 ml/kg forced expiration were 57.8% and 62.1% in the right cranial lobe and right caudal lobe, respectively. In conclusion, bronchial diameter may change during the respiratory cycle, and some degree of reduction in bronchial diameter may be an incidental finding in healthy dogs. More rigorous criteria are needed with regards to bronchial collapsibility during normal respiration for the diagnosis of bronchomalacia in order to avoid false-positive diagnoses.

Effects of neural stem cells and 5-fluorocytosine in canine metastatic lung tumor.

This is the first case report to describe the tumor regressive effect of systemic human neural stem cell (NSC)/5-fluorocytosine (5-FC) therapy on canine metastatic lung tumor. The therapeutic effects appeared approximately two weeks after 5-FC administration. Thoracic radiographs revealed a reduced number of lung nodules and decreased nodule size. However, there were no significant antitumor effects on primary lesions in abdominal organs. In conclusion, human NSC/5-FC prodrug therapy can secure patient quality of life with the same or more therapeutic effects and fewer side effects than other recommended chemotherapies.

Evaluation of computed tomographic enterography with an orally administered lactulose solution in clinically normal dogs.

OBJECTIVE: To determine optimal techniques for CT enterography in clinically normal dogs and to evaluate luminal distention after oral administration of lactulose solution as a contrast agent. ANIMALS: 15 healthy dogs. PROCEDURES: CT was performed in a control group (2 dogs that underwent CT to evaluate metastasis and 5 other dogs). In a bolus administration group (5 dogs from the control group), lactulose solution (1.34 g/mL) was administered (60 mL/kg) rapidly via gastric tube to anesthetized dogs, and CT was performed every 10 minutes for 1 hour. In a continuous administration group of 8 other dogs, lactulose solution (60 mL/kg) was administered slowly via nasoesophageal tube over a period of 45 minutes. Then, 15 minutes after anesthetic induction, CT was performed every 10 minutes for 1 hour. Luminal distention of the small intestines was evaluated qualitatively by use of a 3-point scale. RESULTS: All small intestinal segments had poor luminal distention in the control group. The terminal ileum had poor luminal distention for the bolus administration group. Nearly all segments had good luminal distention for the continuous administration group with mild adverse effects. Luminal distention scores from 0 to 20 minutes after lactulose administration were significantly higher than scores from 30 to 60 minutes. Interobserver reproducibility was high for all intestinal segments. CONCLUSIONS AND CLINICAL RELEVANCE: CT performed between 0 and 20 minutes after continuous administration of lactulose solution (60 mL/kg) may reveal adequate luminal distention for examination of small intestinal segments in dogs.

High-resolution fluorodeoxyglucose positron emission tomography and magnetic resonance imaging findings of a pituitary microtumor in a dog.

A 16-year-old, castrated, male English cocker spaniel dog was presented due to generalized alopecia. Routine clinical pathology, endocrine and abdominal ultrasonography results were consistent with a diagnosis of pituitary-dependent hyperadrenocorticism. The adenohypophyseal lesion was clearly visualized on both 3 T and 7 T magnetic resonance imaging (MRI) of the pituitary gland. Although biochemical and MRI findings were consistent with a functional pituitary microtumor, a pituitary lesion was not detected using (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET). This report firstly describes the application of high-resolution FDG-PET to a spontaneous pituitary microtumor in a dog.

Basosquamous carcinoma with systemic metastasis in a miniature Pinscher.

Basosquamous carcinoma (BSCC) is a rare malignancy, primarily composed of basal cells with foci of squamous differentiation. It is considered to be histologically an intermediate type between basal cell carcinoma and squamous cell carcinoma, and is known to have aggressive behaviors. BSCC occurred in a 17-year-old female minipin with a history of surgical excision for a mammary tumor. The right upper hindlimb was severely enlarged to 8 x 5 cm. Cross-section showed a homogenous white to yellow-white mass compressing the surrounding muscular tissues. The tumor metastasized also to the lungs, heart, abdominal cavity, liver and salivary gland. Microscopically, basaloid cells were crowded into solid nests or lobules separated by well-developed fibrous tissues with occasional keratinizations. Since there was no skin lesions, the tumor is assumed to be originated from the formerly present tumor in mammary gland. To our literature review, this case is the first BSCC with systemic metastasis in a dog.

Treatment of hydrocephalus with high-pressure valve ventriculoperitoneal shunt in a dog.

A 5-month-old male Maltese with right-sided circling, deafness, and blindness was presented. A diagnosis of communicating hydrocephalus was made. A ventriculoperitoneal shunt was implanted and the cerebrospinal fluid was drained by using an adjustable valve type (Medtronic Strata). The valve was set at 2.5 (135-155 mmH2O). This was done to prevent the possibility of an overdrainage-induced collapse of the brain parenchyma, which can occur rarely when canine hydrocephalus is treated by using a low-pressure valve. Computed tomography performed 6 weeks and 1 year after surgery revealed the ventricles had decreased in size. Thus, a high-pressure valve used during the treatment of hydrocephalus was able to maintain normal intracranial pressure.

What is your diagnosis? Ascites fluid from an 11-year-old dog with epigastric bulging.

An 11-year-old, intact female, Yorkshire Terrier dog was presented with epigastric bulging. Results of a CBC included mild neutrophilia and thrombocytopenia. Radiographic examination and abdominal ultrasonography revealed abundant ascites and a well-circumscribed mass in the caudal region of the spleen. Abdominocentesis revealed bloody fluid. Cytologic analysis of the fluid revealed numerous clustered and individual large cells with moderate anisocytosis and anisokaryosis. The spleen was surgically resected. An imprint smear of a white nodular tumor on the caudal pole of the spleen contained a bimorphic population of small and large lymphocytes. The cytologic diagnosis was lymphoma. Histologically, large lymphocytes with distinct borders and single nucleoli formed multiple neoplastic follicles. The final diagnosis was primary splenic lymphoma. Immunocytochemical staining results on buffy coat smears prepared from the ascites fluid showed the lymphocytes were negative for CD3 and positive for CD79a, indicating B-cell origin. Further investigation of the cell clusters using semiquantitative reverse transcriptase-PCR showed that ICAM-1, a cell-cell adhesion molecule, was overexpressed in the tumor cells, likely contributing to the clustering of neoplastic lymphocytes in the ascites fluid. Usually, round cells are not adherent; however, spontaneously detached round cells may form clusters, as in this case, and must be differentiated from epithelial tumors.

The "no-drill" technique of anterior clinoidectomy: a cranial base approach to the paraclinoid and parasellar region.

INTRODUCTION: A high-speed power-drilling technique of anterior clinoidectomy has been advocated in all publications on paraclinoid region surgery. The entire shaft of the power drill is exposed in the operative field; thus, all neurovascular structures in proximity to any portion of the full length of the rotating drill bit are at risk for direct mechanical and/or thermal injury. Ultrasonic bone removal has recently been developed to mitigate the potential complications of the traditional power-drilling technique of anterior clinoidectomy. However, ultrasound-related cranial neuropathies are recognized complications of its use, as well as the increased cost of device acquisition and maintenance. METHODS: A retrospective review of a cerebrovascular/cranial base fellowship-trained neurosurgeon's 45 consecutive cases of anterior clinoidectomy using the "no-drill" technique is presented. Clinical indications have been primarily small to giant aneurysms of the proximal internal carotid artery; however, in addition to ophthalmic segment aneurysms, selected internal carotid artery-posterior communicating artery aneurysms and internal carotid artery bifurcation aneurysms, and other large/giant/complex anterior circulation aneurysms, this surgical series of "no-drill" anterior clinoidectomy includes tuberculum sellae meningiomas, clinoidal meningiomas, cavernous sinus lesions, pituitary macroadenomas with significant suprasellar extension, other perichiasmal lesions (sarcoid), and fibrous dysplasia. A bony opening is made in the mid-to posterior orbital roof after the initial pterional craniotomy. Periorbita is dissected off the bone from inside the orbital compartment. Subsequent piecemeal resection of the medial sphenoid wing, anterior clinoid process, optic canal roof, and optic strut is performed with bone rongeurs of various sizes via the bony window made in the orbital roof. RESULTS: No power drilling was used in this surgical series of anterior clinoidectomies. Optimal microsurgical exposure was obtained in all cases to facilitate complete aneurysm clippings and lesionectomies. There were no cases of direct injury to surrounding neurovascular structures from the use of the "no-drill" technique. The surgical technique is presented with illustrative clinical cases and intraoperative photographs, demonstrating the range of applications in anterior and central cranial base neurosurgery. CONCLUSION: Power drilling is generally not necessary for removal of the anterior clinoid process, optic canal roof, and optic strut. Rigorous study of preoperative computed tomographic scans/computed tomographic angiography scans, magnetic resonance imaging scans, and angiograms is essential to identify important anatomic relationships between the anterior clinoid process, optic strut, optic canal roof, and neighboring neurovascular structures. The "no-drill" technique eliminates the risks of direct power-drilling mechanical/ thermal injury and the risks of ultrasound-associated cranial neuropathies. The "no-drill" technique provides a direct, time-efficient, and efficacious approach to the paraclinoid/ parasellar/pericavernous area, using a simplified mechanical route. This technique is applicable to any neurosurgical diagnosis and approach in which anterior clinoidectomy is necessary. It is arguably the gentlest and most efficient method for exposing the paraclinoid/parasellar/pericavernous region.

Chronic hypopituitarism after traumatic brain injury: risk assessment and relationship to outcome.

OBJECTIVE: Chronic pituitary dysfunction is increasingly recognized as a sequela of traumatic brain injury. We sought to define the incidence, risk factors, and neurobehavioral consequences of chronic hormonal deficiencies after complicated mild, moderate, or severe traumatic brain injury. METHODS: Patients aged 14 to 80 years were prospectively enrolled at the time of injury and assessed at 3 and 6 to 9 months after injury for hormonal function and neurobehavioral consequences. Major and minor (subclinical) hormonal deficiencies, including growth hormone deficiency (GHD) and growth hormone insufficiency (GHI), were identified. Acute injury characteristics, neurobehavioral, and quality of life measures were compared in patients with and without major hormonal deficits by the use of multivariate analysis. RESULTS: Out of 70 patients (mean age, 32 yr; median Glasgow Coma Scale score, 7; 19% women) tested at 6 to 9 months after injury, 15 (21%) had at least one major hormonal deficiency, 20 (29%) had minor deficiencies, and 30 (43%) had major and/or minor deficiencies. Patients with major deficiencies included 16% with GHD or GHI, 10.5% with hypogonadism, and 1.4% with diabetes insipidus. None of the patients required adrenal or thyroid replacement. At 6 to 9 months after injury, patients with major hormonal deficits had more abnormal acute computed tomographic findings (P = 0.014), greater acute and chronic body mass index (P < 0.01), and a worse Disability Rating Scale score (multivariate P = 0.04). Compared with the 59 growth hormone-sufficient patients, the 11 patients with GHD or GHI had worse Disability Rating Scale scores (multivariate P = 0.04), greater rates of depression, (90 versus 53%; multivariate P = 0.06), and worse quality of life in the Short Form-36 domains of energy and fatigue (multivariate P = 0.03), emotional well-being (multivariate P = 0.02), and general health (multivariate P = 0.07). CONCLUSION: Chronic hypopituitarism warranting hormone replacement occurs in approximately 20% of patients after complicated mild, moderate, or severe traumatic brain injury and is associated with more severe brain injuries and increased disability. GHD and GHI are also associated with increased disability, poor quality of life, and a greater likelihood of depression. The clinical significance of minor hormonal deficits, which occur in almost 30% of patients, warrants further study. Given that major deficiencies are readily treatable, routine pituitary hormonal testing within 6 months of injury is indicated for this patient population.

Gene expression in blood changes rapidly in neutrophils and monocytes after ischemic stroke in humans: a microarray study.

Ischemic brain and peripheral white blood cells release cytokines, chemokines and other molecules that activate the peripheral white blood cells after stroke. To assess gene expression in these peripheral white blood cells, whole blood was examined using oligonucleotide microarrays in 15 patients at 2.4+/-0.5, 5 and 24 h after onset of ischemic stroke and compared with control blood samples. The 2.4-h blood samples were drawn before patients were treated either with tissue-type plasminogen activator (tPA) alone or with tPA plus Eptifibatide (the Combination approach to Lysis utilizing Eptifibatide And Recombinant tPA trial). Most genes induced in whole blood at 2 to 3 h were also induced at 5 and 24 h. Separate studies showed that the genes induced at 2 to 24 h after stroke were expressed mainly by polymorphonuclear leukocytes and to a lesser degree by monocytes. These genes included: matrix metalloproteinase 9; S100 calcium-binding proteins P, A12 and A9; coagulation factor V; arginase I; carbonic anhydrase IV; lymphocyte antigen 96 (cluster of differentiation (CD)96); monocarboxylic acid transporter (6); ets-2 (erythroblastosis virus E26 oncogene homolog 2); homeobox gene Hox 1.11; cytoskeleton-associated protein 4; N-formylpeptide receptor; ribonuclease-2; N-acetylneuraminate pyruvate lyase; BCL6; glycogen phosphorylase. The fold change of these genes varied from 1.6 to 6.8 and these 18 genes correctly classified 10/15 patients at 2.4 h, 13/15 patients at 5 h and 15/15 patients at 24 h after stroke. These data provide insights into the inflammatory responses after stroke in humans, and should be helpful in diagnosis, understanding etiology and pathogenesis, and guiding acute treatment and development of new treatments for stroke.