Nonsurgical Disorders of the Brain and Spine

Chapter 43


Nonsurgical Disorders of the Brain and Spine


There are a number of nonsurgical disorders of the brain and spine that neurosurgeons need to be familiar with because (1) these disorders can mimic surgical disorders and are often presented as such for diagnosis and possible surgery and (2) some of these disorders require imminent diagnosis and treatment for a positive outcome. If presented with such patients, it is incumbent on the neurosurgeon to either be comfortable in diagnosing and treating these animals or to quickly recognize the nature of the disease process and arrange for care with the appropriate specialist. In some cases a biopsy will be required for diagnosis. Although currently done infrequently, the use of stereotactic brain biopsy equipment that interfaces with both magnetic resonance imaging (MRI) and computed tomography (CT) is increasingly being used in veterinary neurosurgery. The distinction between surgical and nonsurgical disease of the brain and spine is not always clear; diskospondylitis is usually considered to be solely a medical disorder; however, some patients will develop compressive lesions (e.g., infected epidural fat) and/or vertebral instability, either of which may require surgical intervention.



Specific Diseases



Cognitive Dysfunction Syndrome




General Considerations and Clinically Relevant Pathophysiology


Cognitive dysfunction syndrome (CDS) is an age-related disorder similar to Alzheimer’s disease (AD) in people that occurs in elderly dogs and cats. Cognitive dysfunction syndrome is best described for the dog, and this species appears to be the best animal model available for human AD. Similar to AD in people, the pathophysiology of CDS is uncertain. There are pathologic similarities between the brains of humans with AD and dogs and cats with CDS. Cerebral vascular changes, meningeal thickening, gliosis, and ventricular dilatation occur in brains of both AD and CDS patients. More specifically, progressive accumulation of a neurotoxic protein called beta-amyloid (Aβ) in the brain (in and around neurons) is a consistent feature in both AD and CDS. These accumulations coalesce to form plaques (neuritic plaques) and are most prominent in the frontal cerebral cortex and hippocampus in both human and veterinary disorders. In both disorders, the degree of Aβ accumulation correlates with the extent of cognitive impairment. In addition to the accumulation of neurotoxic Aβ (protein in the aged canine and feline brain, intraneuronal accumulation of a hyperphosphorylated microtubular-associated protein (tau protein) has also been demonstrated. Tau protein is the precursor to neurofibrillary tangles (NFTs), another prominent histopathologic feature of human AD. The absence of mature NFTs in the brains of dogs and cats with CDS has been argued as evidence against CDS of dogs and cats being analogous to human AD. However, the absence of NFTs in dogs and cats has a number of potential explanations. It is possible that dogs and cats do not live long enough for the tau proteins to develop into NFTs as they do in people. Although the amino acid sequence of Aβ protein is identical in humans and dogs, this is not the case for tau protein. The amino acid sequence of dogs and cats differs from that in people; this different sequence may affect the ability of tau protein to form NFTs. Other structural abnormalities found in the aging canine brain that are similar to those in humans include cerebral atrophy, ventricular enlargement, blood vessel wall fibrosis, and amyloid deposition (meningeal and parenchymal), microhemorrhages and infarcts, axonal degeneration with myelin loss, astroglial hypertrophy and hyperplasia, and intraneuronal accumulation of several substances (lipofuscin, polyglucosan bodies, and ubiquitin).


The pathophysiology of CDS and AD is multifactorial and complex. There is evidence in both diseases that increased oxygen-free radical mediated cellular damage, decreased endogenous antioxidant defenses, inflammation (from various processes), decreased mitochondrial function, DNA damage, vascular compromise, and neurotransmitter imbalance are all interrelated processes that are involved in progressive cognitive impairment. Neurochemical changes that occur in the aging brain are thought to contribute to progressive cognitive impairment. An age-associated decline in the brain neurotransmitter levels of acetylcholine, dopamine, norepinephrine, and gamma–aminobutyric acid (GABA) has been documented in CDS and AD. Of these abnormalities, cholinergic dysfunction appears to have the highest and most consistent correlation with age-related cognitive impairment. Other neurochemical abnormalities identified in brains of CDS and AD patients include increased acetylcholinesterase levels (associated with cholinergic decline), increased monoamine oxidase B (catalyzes the breakdown of dopamine, with subsequent formation of free radicals), and elevated cerebrospinal fluid (CSF) levels of lactate, pyruvate, and potassium.



Diagnosis



Clinical Presentation






Diagnostic Imaging


The only imaging modality of use for the diagnosis of CDS is MRI. Brain imaging of AD patients can be normal or may reveal brain atrophy, ventricular enlargement, and lesions in the medial temporal lobes of the cerebral cortex (Fig. 43-1). Age-related changes appreciated on MR imaging of the brain in CDS patients are primarily reflective of brain atrophy and include ventricular enlargement, widened and well-demarcated cerebral sulci, and diffuse and scattered areas of T2-hyperintensity in periventricular white matter. Although these are consistent findings associated with the aging brain, they may be found in older patients without evidence of CDS. The thickness of the interthalamic adhesion as measured on transaxial T1- and T2-weighted MR images was found to be significantly smaller in dogs with CDS compared with dogs without CDS (Fig. 43-2); an interthalamic adhesion thickness of 5 mm or less was found to be consistent with a diagnosis of CDS in dogs (Hasegawa et al, 2005).







Medical Management


There are numerous proposed therapeutic approaches to CDS, with variable evidence of efficacy in improving cognitive function and/or delaying progression of cognitive decline. The use of oral l-deprenyl (selegiline; Anipryl, Atapryl, Carbex, Eldepryl, Zelapar), an irreversible inhibitor of monoamine oxidase B (MAOB), has been purported to improve cognitive function and slow progression of the disease in the majority of dogs and cats with CDS. There is considerable variability in the degree of response achieved among patients, however. l-deprenyl is thought to exert its beneficial effects in the brain by restoring dopaminergic balance as well as enhancing catecholamine levels and decreasing levels of damaging free radical species. The dosage for dogs is 0.5 to 1 mg/kg every 24 hours. Cats are administered 0.5 mg/kg every 24 hours. Most patients will exhibit a positive response within the first month of therapy. Despite apparent positive responses of both canine and feline CDS patients to selegiline, there is evidence that this drug does not have a significant effect on cognitive function in these patients or in people with AD. The clinical efficacy studies supporting selegiline use in CDS are based primarily on owner response to questionnaires rather than on standardized comparative cognitive testing procedures of treated and untreated patients. Because selegiline may produce nonspecific low-level hyperactivity by increasing brain catecholamine levels, the “response” observed by owners may not truly be representative of improved cognitive ability. Selegiline is not considered an effective drug for human AD, because of variable responses and overall minimum improvement of cognitive function. The acetylcholinesterase inhibitor phenserine has exhibited efficacy in improving cognitive function in both dogs with CDS and humans with AD in clinical trials; to the author’s knowledge, this drug is not yet commercially available for dogs. Behavioral changes in CDS patients may be alleviated with the use of GABA-ergic drugs, such as gabapentin or pregabalin. Because inflammatory changes have been identified in the brains of CDS dogs, the use of anti-inflammatory drugs (e.g., carprofen) has also been proposed. Some naturally occurring phytochemicals (e.g., curcumin, resveratrol, green tea catechins) may hold some promise as treatment options for CDS. Oral S-adenosylmethionine (SAMe) has been shown to be effective in improving clinical signs of mental decline in CDS dogs in one study (Reme et al, 2008). Finally, a large number of complimentary therapies have been suggested for the treatment of CDS, with the primary goals of calming the patient, reducing anxiety, and normalizing the sleep-wake cycle. These include melatonin, valerian root, dog-appeasing pheromone (DAP), phosphatidylserine, ginkgo biloba, DHA (an omega 3 fatty acid), and various antioxidants and mitochondrial cofactors. The evidence for efficacy of these complimentary therapies is entirely anecdotal. There is convincing evidence that providing a diet fortified with antioxidants, mitochondrial cofactors, and essential fatty acids improves cognitive function and delays cognitive decline in dogs with CDS. This commercially available diet (Hills b/d) contains a mixture of fruits and vegetables, in addition to vitamins C and E, and mitochondrial cofactors (L-carnitine, DL-α-lipoic acid). Environmental enrichment, such as regular exercise and introduction of new toys, has also been demonstrated to improve cognitive function and delay cognitive decline in dogs with CDS. Progression of CDS appears to be more rapid in castrated versus intact male dogs, suggesting a potential role for hormone replacement therapy in this disease.






Degenerative Myelopathy




General Considerations and Clinically Relevant Pathophysiology


Degenerative myelopathy (DM) is a heritable (presumed autosomal recessive) progressive degeneration of axons and myelin in all funiculi of the spinal cord, primarily in the thoracolumbar region. Recent evidence (Awano et al, 2009) suggests that DM is the canine analog of human amyotrophic lateral sclerosis (ALS). A genetic mutation in the superoxide dismutase 1 (SOD 1) gene has been identified in dogs with DM; this mutation leads to intraneuronal accumulation of cytotoxic cytoplasmic aggregates that stain with anti-SOD 1 antibodies. Loss of axons with secondary demyelination has been demonstrated in both the central nervous system (CNS) and peripheral nervous system (PNS) of affected dogs. Dogs that are homozygous for the gene mutation are at risk for developing DM.



Diagnosis



Clinical Presentation













Ischemic/Vascular Disease




General Considerations and Clinically Relevant Pathophysiology


There are multiple potential causes for brain infarcts, including systemic hypertension (primary/essential hypertension or secondary to underlying disease such as chronic renal failure, hyperadrenocorticism, or pheochromocytoma), cardiac disease, hypercoagulability, increased blood viscosity (e.g., polycythemia vera, multiple myeloma), intravascular neoplasia (e.g., lymphoma, hemangiosarcoma), infectious disease, and atherosclerosis (e.g., associated with hypothyroidism, diabetes mellitus, or hyperlipidemia). In people with strokes, an underlying cause is not identified in about 40% of cases; these infarcts are termed “cryptogenic.” The percentage of cryptogenic strokes in dogs is believed to be similar to that in people. In contrast to humans, atherosclerosis appears to be rarely associated with canine brain infarcts; when it does occur in dogs, it is most likely to be associated with hypothyroidism. Brain infarcts in dogs are typically nonhemorrhagic and are most common in the cerebellum, cerebrum, and thalamic/midbrain regions. Multifocal brain infarcts have been reported but are comparatively uncommon. Cerebellar and cerebral infarcts tend to be territorial, involving the territories of large arteries such as the rostral cerebellar artery and middle cerebral artery, respectively. These territorial infarcts tend to primarily involve the gray matter with variable levels of white matter involvement. Thalamic/midbrain infarcts tend to be smaller lacunar lesions involving the smaller perforating arteries of this brain region. In one report, over half of the dogs with brain infarcts had an underlying metabolic disorder that could potentially lead to thromboembolic disease, the most common being chronic renal disease and hyperadrenocorticism (Garosi et al, 2005). Systemic hypertension was documented in nearly 30% of those dogs whose blood pressure was documented. In another study of cerebellar infarcts in dogs, systemic hypertension was identified in over 40% of those patients in which blood pressure was measured (Darrin et al, 2006). In the author’s experience there is usually an underlying disease present that could potentially explain the presence of hypertension in these dogs, with chronic renal disease and hyperadrenocorticism being the most common disorders.


Fibrocartilaginous embolic myelopathy is a common syndrome caused by the embolization of arterial and/or venous supply to an area of the spinal cord. The embolizing material has been identified as fibrocartilage and is believed to originate from the nucleus pulposus of the intervertebral disk. The mechanism or mechanisms by which this material reaches the spinal cord vasculature from the disk are unknown. Theories center either around venous entry of disk material (e.g., extrusion either directly into a venous sinus or venous system of vertebral bone marrow—a Schmorl’s node) with retrograde movement into the spinal arterial system (Fig. 43-3), or direct entry to the spinal cord arterial system (e.g., into normal surrounding vasculature or neovascularization over the annulus fibrosus associated with concomitant type II disk degeneration).


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Sep 11, 2016 | Posted by in SMALL ANIMAL | Comments Off on Nonsurgical Disorders of the Brain and Spine

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