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Ultrasound-guided cervical centesis has gained popularity as a method for collecting cerebrospinal fluid (CSF) from standing horses. There are anecdotal reports of neck stiffness, regional swelling, sensitivity to palpation, and fever after the procedure. We report 2 horses with complications that occurred within days of C1-C2 centesis and ultimately resulted in euthanasia. Both C1-C2 centesis were performed routinely, with CSF cytologic analysis providing no evidence of blood contamination. Post-mortem examination revealed equine degenerative myeloencephalopathy as the primary disorder causing Horse 1's initial neurologic deficits, whereas Horse 2 did not have a distinct lesion explaining the horse's deficits. Both horses had evidence of subarachnoid hemorrhage at or near the centesis site with Wallerian axonal degeneration in the cranial cervical spinal cord. Although hemorrhage with associated axonal degeneration at the cervical centesis site appears to be rare, this complication of C1-C2 centesis should be considered as this technique gains popularity.

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Brain aneurysm ruptured subarachnoid hemorrhages (SAH) are extremely rare except in humans. This study described a SAH caused by a ruptured anterior communication artery aneurysm and concurrent myocardial infarction, along with pneumonia and intestinal obstruction in a rhesus monkey, which is rather rare in animal experiments.

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BACKGROUND: Concepts that showed substantial efficacy in animal models of subarachnoid hemorrhage (SAH) often failed to improve outcome in humans with aneurysmal SAH. The concept of "comparative medicine," an open-minded comparison across species, might offer an alternative to the "constructed" animal models' approach. Naturally occurring diseases in animals might bear more similarity to human diseases than models. In this context, the question arises whether spontaneous intracranial aneurysms exist in animals or not, and whether they cause SAH or not. METHODS: A systematic literature search was performed. Only articles dealing with natural aneurysms and/or SAH of mammals other than man were included. All articles dealing with induced aneurysms and/or SAH were removed. RESULTS: Of 2812 screened articles, 9 articles describing natural intracranial aneurysms and/or SAH were found. In total 1979 individual animals of 29 species were examined. Natural intracranial aneurysms were described in 7 individual animals of 6 species. Spontaneous SAH was described in 3 species. In 1 chimpanzee, a ruptured intracranial aneurysm caused an SAH. Histological descriptions of the aneurysms were strikingly similar to those of humans. CONCLUSIONS: Although interesting and innovative, the concept of "comparative medicine" seems to be impracticable due to the seemingly ultralow incidence of natural aneurysmal SAH in mammals other than man. The answer to the question "why intracranial aneurysms are less common in animals despite the strong histological similarity of cerebral arteries" might be a key issue. Last but not least, primates likely matter in SAH-related research, as aneurysmal SAH occurs in primates.

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Objective: Cerebral vasospasm, one of the main complications of subarachnoid hemorrhage (SAH), is characterized by arterial constriction and mainly occurs from day 4 until the second week after the event. Urotensin-II (U-II) has been described as the most potent vasoconstrictor peptide in mammals. An analysis is made of the serum U-II concentrations and mRNA expression levels of U-II, urotensin related peptide (URP) and urotensin receptor (UT) genes in an experimental murine model of SAH. Design: An experimental study was carried out. Setting: Experimental operating room of the Biomedicine Institute of Seville (IBiS), Virgen del Rocío University Hospital (Seville, Spain). Participants: 96 Wistar rats: 74 SAH and 22 sham intervention animals. Interventions: Day 1: blood sampling, followed by the percutaneous injection of 100μl saline (sham) or blood (SAH) into the subarachnoid space. Day 5: blood sampling, followed by sacrifice of the animals. Main variables of interest: Weight, early mortality, serum U-II levels, mRNA values for U-II, URP and UT. Results: Serum U-II levels increased in the SAH group from day 1 (0.62pg/mL [IQR 0.36-1.08]) today 5 (0.74pg/mL [IQR 0.39-1.43]) (p<0.05), though not in the sham group (0.56pg/mL [IQR 0.06-0.83] day 1; 0.37pg/mL [IQR 0.23-0.62] day 5; p=0.959). Between-group differences were found on day 5 (p<0.05). The ROC analysis showed that the day 5 serum U-II levels (AUC=0.691), URP mRNA (AUC=0.706) and UT mRNA (AUC=0.713) could discriminate between sham and SAH rats. The normal serum U-II concentration range in rats was 0.56pg/mL (IQR 0.06-0.83). Conclusion: The urotensinergic system is upregulated on day 5 in an experimental model of SAH (AU)

Objetivo: El vasoespasmo cerebral, una de las principales complicaciones secundarias a hemorragia subaracnoidea (HSA), se caracteriza por una constricción arterial que tiene lugar principalmente entre el día 4 y la segunda semana. La urotensina-II (U-II) ha sido definida como el péptido con mayor capacidad vasoconstrictora en mamíferos. Quisimos analizar los niveles séricos de U-II, así como los niveles de expresión de los genes de U-II, péptido relacionado con urotensina y receptor de urotensina, en un modelo murino experimental de HSA. Diseño: Estudio experimental. Ámbito: Quirófano experimental del Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío. Participantes: Noventa y seis ratas Wistar: 74 con inyección percutánea de sangre (HSA), 22 con inyección percutánea de 100μL de salino (Sham). Intervenciones: Día 1: extracción de muestras de sangre. Posteriormente, inyección percutánea de 100μL de salino (Sham) o de sangre (HSA) en el espacio subaracnoideo. Día 5: extracción de muestras de sangre y sacrificio del animal. Principales variables de interés: Peso, mortalidad precoz, niveles séricos de U-II, valores de ARNm de U-II, péptido relacionado con urotensina y receptor de urotensina. Resultados: Observamos un incremento en los niveles de U-II sérica en el grupo HSA desde el día 1 (0,62pg/mL [RI 0,36-1,08]) al día 5 (0,74pg/mL [RI 0,39-1,43]) (p<0,05); pero no observamos tal diferencia en el grupo Sham (0,56pg/mL [RI 0,06-0,83] día 1; 0,37pg/mL [RI 0,23-0,62] día 5) (p=0,959). Se encontraron diferencias en los niveles de U-II entre ambos grupos al quinto día (p<0,05). El análisis de curvas ROC demostró que la U-II sérica al quinto día (AUC=0,691), ARNm de péptido relacionado con urotensina (AUC=0,706) y ARNm de receptor de urotensina (AUC=0,713) podían discriminar entre ratas Sham y HSA. Además, definimos un rango de normalidad para los niveles de U-II séricos en ratas: 0,56pg/mL (RI 0,06-0,83). Conclusión: Este estudio demuestra por primera vez que el sistema urotensinérgico ve incrementada su expresión en el quinto día en un modelo de HSA (AU)

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A 13-year-old, female spayed, crossbreed dog of 32 kg was presented for evaluation of peracute onset of non-ambulatory tetraparesis after chewing an electrical wire. Neurological examination was consistent with a C1-C5 myelopathy. Magnetic resonance imaging revealed a focal intramedullary lesion over the C2-C3 vertebral bodies, which was confirmed to be an acute focal necrotising poliomyelopathy with subarachnoid and subdural haemorrhages on postmortem examination. This report describes the clinical, imaging and histopathological findings of this unusual type of spinal cord injury, and the effects of electrocution in the central nervous system of dogs.

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OBJECTIVE: To measure concentrations of glutamate, aspartate, γ-aminobutyric acid (GABA), and glycine in CSF of dogs with experimentally induced subarachnoid hemorrhage (SAH) and to assess effects of cyclosporine and simvastatin on these concentrations. SAMPLE: CSF samples from 13 dogs. PROCEDURES: In a previous study, SAH was induced in dogs via 2 injections of autologous blood into the cerebellomedullary cistern 24 hours apart. Dogs were untreated (control; n = 5) or received simvastatin alone (4) or simvastatin in combination with cyclosporine (4). Samples of CSF were collected before the first blood injection (baseline; time 0), before the second blood injection, and on days 3, 7, and 10. For the study reported here, neurotransmitter concentrations in CSF were analyzed via high-performance liquid chromatography. Data were analyzed with a repeated-measures model with adjustments for multiple comparisons by use of the Tukey method. RESULTS: In control dogs, the glutamate concentration peaked on day 3 and there was a significant increase in GABA and glutamate concentrations. Glutamate concentrations were significantly lower and glycine concentrations significantly higher on day 3 after administration of simvastatin alone or simvastatin in combination with cyclosporine, compared with concentrations for the control group. No significant differences in GABA and aspartate concentrations were detected among treatment groups at any time point. CONCLUSIONS AND CLINICAL RELEVANCE: Glutamate concentrations were increased in the CSF of dogs with SAH. Simvastatin administration attenuated high glutamate concentrations. A combination of immunosuppression and upregulation of nitric oxide synthase may be useful in lowering high glutamate concentrations in ischemic CNS conditions.

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Rotational inertial forces are thought to be the underlying mechanism for most severe brain injuries. However, little is known about the effect of head rotation direction on injury outcomes, particularly in the pediatric population. Neonatal piglets were subjected to a single non-impact head rotation in the horizontal, coronal, or sagittal direction, and physiological and histopathological responses were observed. Sagittal rotation produced the longest duration of unconsciousness, highest incidence of apnea, and largest intracranial pressure increase, while coronal rotation produced little change, and horizontal rotation produced intermediate and variable derangements. Significant cerebral blood flow reductions were observed following sagittal but not coronal or horizontal injury compared to sham. Subarachnoid hemorrhage, ischemia, and brainstem pathology were observed in the sagittal and horizontal groups but not in a single coronal animal. Significant axonal injury occurred following both horizontal and sagittal rotations. For both groups, the distribution of injury was greater in the frontal and parietotemporal lobes than in the occipital lobes, frequently occurred in the absence of ischemia, and did not correlate with regional cerebral blood flow reductions. We postulate that these direction-dependent differences in injury outcomes are due to differences in tissue mechanical loading produced during head rotation.

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OBJECTIVE: Cerebral vasospasm remains a major cause of morbidity and mortality. Milrinone, a bipyridine phosphodiesterase III inhibitor, is a potent member of the inodilator class of cardiac agents for vasospasm and is injected intra-arterially or intracisternally. There have been no studies investigating the duration of action (context-sensitive half-life) of milrinone for vasospasm or the most effective route of administration (intra-arterial versus intracisternal). We examined the effects of intracisternal and intra-arterial injection of milrinone on chronic cerebral vasospasm in dogs. METHODS: A double-hemorrhage canine model was used. In a preliminary isometric tension study of canine vasospastic basilar arteries, the vasodilatory effects of milrinone were examined 7 days after an initial injection of blood. Milrinone was injected intracisternally (0.1 mg, 0.47 mmol/L) or intra-arterially (0.3 mg/kg, 1.2 mmol/L), and angiograms were performed 30, 60, 120, 180, 240, 300, and 360 minutes later on day 7. RESULTS: Milrinone produced concentration-dependent vasodilation and was effective intracisternally, resulting in significant dilation until 180 minutes after injection and a tendency for dilation until 240 minutes. The effect of intra-arterial injection was not as significant compared with an intracisternal injection, resulting in significant dilation only at 180 minutes after intra-arterial injection. CONCLUSION: Intracisternal injection of milrinone was more effective than intra-arterial injection for chronic cerebral vasospasm in dogs because intracisternal injection produced a higher concentration in vasospastic arteries (0.034-0.068 mmol/L intracisternally versus 0.016 mmol/L intra-arterially).

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Intracranial subarachnoid hemorrhage is a rare but serious complication of lumbar puncture in humans. Possible sequelae include increased intracranial pressure, cerebral vasospasm, or mass effect, which can result in dysfunction or brain herniation. We describe two dogs that developed intracranial subarachnoid hemorrhage following lumbar myelography. In both dogs, myelography was performed by lumbar injection of iohexol (Omnipaque). Both the dogs underwent uneventful ventral decompressive surgery for disk herniation; however, the dogs failed to recover consciousness or spontaneous respiration following anesthesia. Neurologic assessment in both dogs postoperatively suggested loss of brain stem function, and the dogs were euthanized. There was diffuse subarachnoid hemorrhage and leptomeningeal hemorrhage throughout the entire length of the spinal cord, brain stem, and ventrum of brain. No evidence of infectious or inflammatory etiology was identified. The diagnosis for cause of brain death was acute subarachnoid hemorrhage. Our findings suggest that fatal subarachnoid hemorrhage is a potential complication of lumbar myelography in dogs. The cause of subarachnoid hemorrhage is not known, but may be due to traumatic lumbar tap or idiosyncratic response to contrast medium. Subsequent brain death may be a result of mass effect and increased intracranial pressure, cerebral vasospasm, or interaction between subarachnoid hemorrhage and contrast medium.

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OBJECT: Increased cerebrospinal fluid (CSF) levels of asymmetric dimethyl L-arginine (ADMA), an endogenous inhibitor of endothelial nitric oxide synthase (eNOS), are associated with delayed vasospasm after subarachnoid hemorrhage (SAH); however, the source, cellular mechanisms, and pharmacological inhibition of ADMA production following SAH are unknown. METHODS: In an in vitro experiment involving human umbilical vein endothelial cells (HUVECs), the authors examined mechanisms potentially responsible for increased ADMA levels during vasospasm and investigated whether this increase can be inhibited pharmacologically. In a second study, an in vivo experiment, the authors used probucol, which effectively inhibited ADMA increase in HUVEC cultures in vitro, in a randomized double-blind placebo-controlled experiment in a primate model of delayed cerebral vasospasm after SAH. Oxidized low-density lipids (OxLDLs; positive control; p < 0.02) and bilirubin oxidation products (BOXes; p < 0.01), but not oxyhemoglobin (p = 0.74), increased ADMA levels in HUVECs. Probucol inhibited changes in ADMA levels evoked by either OxLDLs (p < 0.001) or BOXes (p < 0.01). Comparable changes were observed in cell lysates. In vivo probucol (100 mg/kg by mouth daily) did not alter serum ADMA levels on Days 7, 14, and 21 after SAH compared with levels before SAH, and these levels were not different from those observed in the placebo group (p = 0.3). Despite achieving therapeutic levels in plasma and measurable levels in CSF, probucol neither prevented increased CSF ADMA levels nor the development of vasospasm after SAH. Increased CSF ADMA and decreased nitrite levels in both groups were strongly associated with the degree of delayed vasospasm after SAH (correlation coefficient [CC] 0.5, 95% confidence interval [CI] 0.19-0.72, p < 0.002 and CC -0.43, 95% CI -0.7 to -0.05, p < 0.03, respectively). CONCLUSIONS: Bilirubin oxidation products, but not oxyhemoglobin, increased ADMA levels in the HUVEC. Despite its in vitro ability to lower ADMA levels, probucol failed to inhibit increased CSF ADMA and decreased nitrite levels, and it did not prevent delayed vasospasm in a primate SAH model.

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OBJECT: Results of prior studies in rats and rabbits show that the alteration of vasomotor tone in vasospasm following periadventitial blood exposure may be reversed, at least in part, by the administration of compounds releasing nitric oxide (NO). The authors have now generalized this finding to nonhuman primates. METHODS: Ten cynomolgus monkeys underwent cerebral angiography before and 7 days following the induction of subarachnoid hemorrhage (SAH) by the placement of 2 to 3 ml clotted autologous blood around the supraclinoid carotid, proximal anterior cerebral, and proximal middle cerebral arteries. An ethylene vinyl acetate copolymer, either blank (five animals) or containing 20% w/w (Z)-1-[2-(2-aminoethyl)-N-(2-aminoethyl)amino]diazen-1-ium-1,2-diolate (DETA/NO, 4.3 mg/kg; five animals) was placed adjacent to the vessels at the time of surgery. Animals were killed on Day 7 post-SAH following repeated cerebral angiography. The mean percentage of control vascular areal fraction was calculated from angiograms. Cerebral vessels were sectioned and the mean percentage of lumen patency was calculated. One animal that had received the DETA/NO polymer died prior to repeated angiography. In the remaining animals, DETA/NO caused a significant decrease in vasospasm compared with controls, according to both angiographic (84.8 +/- 8.6 compared with 56.6 +/- 5.2%, respectively, p < 0.05) and histological studies (internal carotid artery 99.3 +/- 1.8 compared with 60.1 +/- 4.4%, respectively, p < 0.001; middle cerebral artery 98.4 +/- 3 compared with 56.1 +/- 3.7%, respectively, p < 0.001; and anterior cerebral artery 89.2 +/- 8.5 compared with 55.8 +/- 6.3%, respectively, p < 0.05). CONCLUSIONS: The controlled release of DETA/NO is effective in preventing delayed cerebral vasospasm in an SAH model in nonhuman primates. The death of one animal in the treatment group indicates that the present dosage is at the threshold between therapeutic efficacy and toxicity.

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OBJECT: The aim of this project was to study the perturbations of four smooth-muscle proteins and an extracellular protein, type I collagen, after subarachnoid hemorrhage (SAH) and to examine the possible preventive effects of dexamethasone. METHODS: Using a one-hemorrhage rabbit model, the authors first examined the effects of SAH on the expression of alpha-actin, h-caldesmon, vimentin, smoothelin-B, and type I collagen; second, they studied whether post-SAH systemic administration of dexamethasone (three daily injections) corrected the induced alterations. Measurements were obtained at Day 7 post-SAH. The proteins were studied by performing immunohistochemical staining and using a laser-scanning confocal microscope. Compared with control (sham-injured) arteries, the density of the media of arteries subjected to SAH was reduced for alpha-actin (-11%, p = 0.01) and h-caldesmon (-15%, p = 0.06) but increased for vimentin (+15%, p = 0.04) and smoothelin-B (+53%, p = 0.04). Among animals in which SAH was induced, arteries in those treated with dexamethasone demonstrated higher values of density for alpha-actin (+13%, p = 0.05) and h-caldesmon (+20%, p = 0.01), lower values for vimentin (-55%, p = 0.05), and nonsignificantly different values for smoothelin-B. The density of type I collagen in the adventitia decreased significantly after SAH (-45%, p = 0.01), but dexamethasone treatment had no effect on this decrease. CONCLUSIONS: The SAH-induced alterations in the density of three of four smooth-muscle proteins were prevented by dexamethasone treatment; two of these proteins--alpha-actin and h-caldesmon--are directly related to contraction. This drug may potentially be useful to prevent certain morphological and functional changes in cerebral arteries after SAH.

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Marginal siderosis is recognized in humans as an uncommon clinicopathologic entity characterized by degeneration of neural tissue at the surface of the brain and spinal cord, in association with the accumulation of hemosiderin, and resulting from chronic subarachnoid hemorrhage. The sources of hemorrhage are various and include neoplasms, malformations, cysts, and vasculopathy. Marginal siderosis of the spinal cord due to a myxopapillary ependymoma was diagnosed in a 19-year-old Dutch Warm Blood horse with clinical signs of myelopathy. There is only one previous report of marginal siderosis in the veterinary literature, also in a horse with clinical myelopathy.

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Angiographic spasm of cerebral arteries was produced in dogs by successive injections of cisternal blood 48 hours apart. Angiograms were taken before and after each cisternal injection. There was progressively greater angiographic vasospasm of the basilar artery. Intravenous aminophylline, 10 mg/kg/hr, reversed vessel constriction on the 1st and 3rd day after one injection of cisternal blood. On the 5th day after two blood injections (on Day 1 and Day 3), intravenous aminophylline, nifedipine (1 mg/kg), and intra-arterial bolus injection of 2 mg/kg papaverine failed to reverse the constriction. The intractable constriction produced in this model resembles that found in patients. The calcium antagonist, nifedipine, is as ineffective as the more traditional vasodilators in reversing vasospasm in this model.

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The effect of iopamidol on the leptomeninges was tested and compared with that of metrizamide and normal saline solution in 18 dogs. Pathologic and clinical effects were evaluated at 24 hours and 14 days after cisternal injection of iopamidol, metrizamide, or normal saline solution. Pathologic changes were evaluated by microscopic examination of serial CSF samples and of sections of brain and spinal cord with the leptomeninges intact. Clinical changes were subjectively evaluated. Electromyograms and EEG were performed on each dog after physical and neurologic examination. There were no changes seen in neurologic status, electromyogram, or EEG in any of the dogs immediately after subarachnoid injection nor at 24 hours or 14 days later. Pathologic changes were limited to mild, moderate, or severe patchy hemorrhagic leptomeningitis seen at 24 hours after iopamidol or metrizamide was injected. The severity of changes were judged to be similar with both these agents. The CSF analysis and histologic evaluation of brain and spinal cord sections revealed a neutrophilic response to iopamidol and a mononuclear response to metrizamide. These findings indicate that iopamidol has minimal neurotoxicologic effect on the leptomeninges and therefore has merit as a myelographic agent.

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A high frequency of meningeal lesions was found at autopsy in foals dying perinatally. Such lesions are considered an index of injury to the fetal central nervous system, from trauma and/or hypoxia during birth. Their incidence in the sample examined (26 foals) is similar to that observed in the perinatal mortality of lambs and calves.

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