There are two reasons why non-traumatic vascular lesions in veterinary neurology are not as important as in human neurology: 1) atherosclerosis is a rare familial or endocrine finding; and 2) recovery of central vascular disorders in animals is probably more spectacular because animals have a less prominent pyramidal system. However, the incidence of central nervous system (CNS) vascular disorders in dogs and cats is probably more common than what is found in the literature as a large number make a partial or total recovery and are never diagnosed by necropsy.
Vascularization of the CNS
Basic anatomy is necessary to understand the consequences of vascular disorders of the brain and spinal cord. In dogs, the internal carotids and the basilar artery supply the brain; they anastomose at the level of the arterial circle within the cavernous sinus. A number of vessels arise from the arterial circle, all of which are terminal. The rostral, middle and caudal cerebral arteries vascularize the hemispheres. The cerebellar arteries supply the cerebellum and the brainstem. In cats, numerous branches from the maxillary artery arising from the external carotid arteries replace the internal carotids.
Two dorsal spinal arteries per spinal cord segment run within the dorsolateral sulci and supply blood through the anastomosing arterial rings and the radial arteries, to the dorsal aspect of the white matter parenchyma. One ventral spinal artery runs in the ventral fissure. It supplies the ventral white matter by joining the anastomosing arterial rings and the central gray matter through vertical or central arteries. These continuous spinal arteries are supplied by a variable number of dorsal and ventral radicular arteries fed by the aorta and by the vertebral arteries in the cervical region. An anastomotic intrinsic network draining within the fissures as well as the sulci, provides venous return. The extrinsic veins communicate with the longitudinal vertebral sinuses that course along the floor of the epidural space throughout the length of the vertebral canal. Venous sinuses are connected to the extra vertebral venous system by intervertebral veins and to the basivertebral veins through osseous channels in the vertebrae.
pathophysiology of vascular CNS disorders
Any central nervous system disorder may at some point cause vascular compromise. A growing tumor may induce vascular collapse because of mass effect or it may bleed spontaneously because of fragile neovascularization. An acute disc herniation may induce a sinus rupture and extensive hematorrachia. These are considered secondary vascular disorders. Primary vascular disorders are either traumatic or spontaneous. Non-traumatic vascular lesions may be occlusive (embolization) or hemorrhagic (rupture of vascular integrity). They may be difficult to differentiate because the result is often a mixed lesion, both lesions inducing tissue infarction, mass effect from edema, and various degrees of ischemia.
Clinical presentation
Clinical consequences of vascular disorders depend on vessel involvement (type and size), degree and duration of ischemia, and parenchymal susceptibility to anoxia. Neurons are the most sensitive cell type to ischemia, followed by oligodendrocytes, astrocytes, and microglia. Vascular endothelium is the most resistant. In vascular lesions, edema is both vasogenic in origin, because of abnormal blood/parenchyma barrier permeability, and cytotoxic, because of cell hypoxia.
Deficits may vary from simple temporary dysfunction to death because of cardio-respiratory arrest. Clinical signs generally appear acutely (“apoplexia”), which is one of the diagnostic criteria from other diseases in which onset is usually progressive over a few days or weeks (infection, neoplasm). Clinical signs due to vascular impairment usually stabilize and regress after 24 to 72 hours; this is attributable to diminution of the mass effect secondary to hemorrhage and reorganization or edema resorption. A non-progressive sign is a criterion of vascular disease.
Location of a vascular lesion is important to explain clinical presentation. With brainstem involvement, neurological examination of the cranial nerves will define the exact location and extent of the lesion. With a prosencephalic vascular lesion, clinical signs may vary from simple disorientation to brain death. A unilateral lesion will induce ipsilateral circling, hemi-inattention syndrome, contralateral amaurosis, contralateral hemiparesia/plegia, and hypo/anesthesia (face and body). Cortical neuronal functional or structural lesions may induce seizures from focal to grand mal or status epilepticus. The size of the vascular lesion is not directly related to the intensity of the neurological signs or deficits. However, the destruction of lower motor neuron cell bodies has a poorer prognosis. Neurolocalization may be difficult because of increased intracranial pressure in which conscious state deterioration, abnormal pupillary reflexes, and papillary edema may be present.
With spinal cord involvement, the clinical presentation will be dependent on the cord segment damaged. With C1-C5 and T3-L3 involvement, the presentation will be UMN in all four limbs or in the rear respectively. With C6-T2 and L4-S2 involvement, the presentation will be LMN, respectively in the front limb or in the rear limbs. The presentation may be asymmetric if the lesion is asymmetric. In such a case, the deficits will be ipsilateral to the lesion.
Diagnostic tools
Blood tests that assess coagulation deficits or specific infectious diseases causing coagulopathy are indicated, including CBC, platelet count, coagulation panel, rickettsial serology, Coombs, and liver function tests, as well as lipid panel and thyroid function test.
Tomodensitometry is a non-invasive imaging technique. Initially, an acute infarct produces a subtle hypodense area caused by edema after three to six hours. A mass effect on the falx and ventricular collapse may also be visible especially after three to five days. Some infarcts may be isodense and are visible only after iodine injection. The enhancement appears after 24 to 48 hours and is most evident after one or two weeks especially in the periphery where neovascularization exists. Because a lesion that is hypodense before contrast becomes isodense after contrast (and thus poorly visible), both pre- and post-contrast images must be examined. After two to three weeks, the edema disappears and the lesion becomes isodense. After four to eight weeks, necrosis induces cavitation with a density equally dense to the ventricular system. Parenchymal atrophy can also be visible. Hemorrhage within the lesion will cause an immediate decrease in density, which becomes more marked over several days as the clot organizes and retracts. Hematomas become isodense after one month.
Magnetic resonance imaging is more sensitive than tomodensitometry. Abnormalities are visible within hours because of water content changes. An infarct will be hypointense in T1 and hyperintense in T2. Enhancement will be identical to tomodensitometry. Gadolinium enhances infarcts because of vascular rupture but does not enhance ischemia or edema. Hemoglobin reacts as a paramagnetic molecule. In case of hemorrhage, the intensity of the image is secondary to the form of hemoglobin present, its location (intra or extraerythrocytic), and the setting of the machine (variation in TE and TR values). MR is also suited for evaluation of vascular structures because of its sensitivity to a variety of flow-related phenomena. High quality MRAngiography can be achieved and be displayed like conventional arteriograms whilst being acquired in a totally non-invasive fashion.
Tomodensitometric and MR images (location, size, density/intensity, mass effect, blood brain barrier disruption) of vascular lesions are not sensitive enough to exclude with certainty inflammatory or neoplasic lesions. These findings must be interpreted in the clinical context. In case of difficulty, repeating the images and assessing their changes may help for final diagnosis. The definitive diagnostic method remains a biopsy of the lesion.
Cerebral and medullary non-traumatic vascular disease
Fibrocartilaginous embolism (FCE) of the spinal cord is a syndrome of acute spinal cord infarction caused by embolization of fibrocartilage. The source of emboli is presumed to be extruded intervertebral disc material. FCE has been described in man, dogs and cats. Histopathologic evaluation is necessary to establish a definitive diagnosis of FCE. Arterial or venous intrinsic or extrinsic vasculature may be involved. Based on a literature review of histologically confirmed cases in dogs, this acute non-progressive spinal cord infarction appears to have a high incidence in large and giant breeds of dogs and a high predilection for the spinal intumescences. In addition to histologically confirmed cases, neurology referral centers see many suspected cases of FCE that are based on the elimination of other causes of transverse myelopathy. These cases have similar clinical signs of acute non-progressive dysfunction, often associated with trauma and exercise. However, the suspected group includes fewer giant breeds and more of these dogs have upper motor neuron involvement and intact nociception. Dog size and severity of clinical signs probably contribute to the owner choosing euthanasia in dogs which have had confirmed lesions.
Ischemic neuromyopathy, secondary to embolism of the caudal aorta, occurs in cats with cardiomyopathy and atrial thrombus formation. Although this is a more peripheral nervous vascular disease, occasionally the thrombus can be located very high in the caudal aorta inducing renal and medullar ischemia.
Feline ischemic syndrome is a unilateral cerebral (especially cortical) infarction in cats of any age. The clinical signs are acute and non-progressive and most of them resolve completely. The middle cerebral artery seems to be most often involved. The brain stem is occasionally involved, either concomitantly or separately. CT or MRI may show signs of infarction. The lesion is an ischemic necrosis, sometimes hemorrhagic, bilateral, or multifocal. The cause of ischemia is unclear; cardiomyopathy is definitely not a key factor. Cuterebra migration has been suspected.
Vasculitis, adventitial proliferation and perivascular infiltration, are encountered with inflammatory diseases of infectious (viral, bacterial, protozoan, rickettsial) or non-infectious origin. Thrombophlebitis of bacterial origin, common in large animals, is rare in pets. With rickettsial (Ehrlichiosis, Borreliosis) vasculitis, neurological signs may appear secondary to coagulopathy and disseminated intravascular coagulation. Non-infectious meningo-encephalo-myelitis (granulomatous, breed specific, arteritis or steroid responsive) may show infarctions due to extreme proliferative vasculitis or spontaneous hemorrhage due to vascular rupture.
Coagulopathies of diverse origin may induce spontaneous bleeding of the brain or the cord. Immune mediated thrombocytopenia, hereditary hemophilia, and vitamin K antagonistic intoxication are the most commonly encountered.
Degenerative vascular diseases are uncommon in pets. Thiamine deficiency, rarely encountered today because of industrial food usage, induces spontaneous hemorrhage of the diencephalons. Arteriosclerosis described in pets is of the non-lipidic form. The lipidic form of arteriosclerosis, named atherosclerosis, is common in humans and may be encountered in hypothyroid dogs. Coronary and renal arteries are generally involved. Hypercholesterolemia, lipemia and hypothyroidism are the three most common laboratory findings. The gross lesions are atherosclerosis, thrombus formation, and obstruction of cerebral circle arteries associated with hemispheric infarction. Idiopathic hyperlipoproteinemia in Miniature Schnauzers also increases the prevalence of atherosclerosis. This is due to the presence of a larger fraction of low-density lipoproteins. Non lipidic arteriosclerosis shows fibrosis especially in the aged animal associated with amyloidosis and mineralization. Arteriosclerosis secondary to systemic hypertension explains central signs encountered in endocrinopathies (hypo-and hyperthyroidism, hyperadrenocorticism, renal insufficiency). Spontaneous hemorrhage may occur secondary to arterial weakening in these diseases. Hyperlipoproteinemia or hyperviscosity could potentially lead to parenchymal ischemia of the CNS.
Some congenital or acquired vascular abnormalities may acutely decompensate and induce large hemorrhages in the brain or the cord. This can be found in aneurysms or cavernous malformations, telangiectasic hemartomas and arterio-venous malformations associated with systemic hypertension or minor trauma.
Some CNS neoplasms may induce acute deterioration because of significant hemorrhage. Pituitary macroadenoma is one example (pituitary apoplexia).
Treatment possibilities
Oxygen and assisted ventilation is mandatory to maintain cerebral blood flow especially if the intracranial pressure is increased. Lowering pCO2 by ventilation induces vasoconstriction of normal brain regions and increases perfusion to ischemic regions. The impairment of cerebral blood flow autoregulation may induce brain hypoperfusion or, conversely, increase intracranial pressure. Emergency treatment against edema and ischemia has to be started as soon as possible. It is important to determine if bleeding is still active, because the use of mannitol would not be indicated if bleeding is persistent. Its osmotic effect may increase the actual size of the hemorrhage although it may, at the same time, decrease the size of the parenchymal edema and increase cerebral blood flow. If the imaging technique does not show bleeding, or if such images cannot be acquired but deterioration is progressive, mannitol should be given at 1.0 g/Kg within 30 minutes IV in case of brain herniation, or more slowly to prolong its beneficial effect. It should be followed by 0.7 mg/Kg of Furosemide IV.
Methyl prednisolone must be started within less than eight hours to protect spinal cord parenchyma against ischemia and free radical formation (30 mg/Kg and then 5.4 mg/Kg/h during 24 hours) if it is to be beneficial. Short acting steroids at an anti-inflammatory dosage are suitable against edema.
Because of lowered immunity and autonomic digestive impairment that is often seen with central nervous system diseases, antibiotic protection, antacid and prostaglandin use is recommended. Diazepam, Midazolam and Phenobarbital are recommended to control seizure activity. Decompressive surgery is recommended in case of large hemorrhage.
At the same time, once the cause of the vascular accident has been determined, the treatment of the underlying disease must be initiated.
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