Cognitive Dysfunction Syndrome

References

Definitions

Degenerative myelopathy is an inherited degenerative disorder of the spinal cord, primarily affecting the thoracolumbar region (T3-L3 segments).

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

Differential Diagnosis

Major differential diagnoses for DM are chronic type II disk protrusion and spinal neoplasia.

Medical Management

No proved effective therapies are available for DM. Treatment is supportive care. Intensive daily physiotherapy may improve survival time in DM dogs.

Surgical Treatment

This is a nonsurgical disorder; there is no surgical treatment for DM.

Prognosis

The disease usually progresses over a 6- to 12-month period, eventually reaching a point at which the patient is nonambulatory in the pelvic limbs. The disease can progress to involve the thoracic limbs and eventually the brainstem in dogs kept alive after this degree of deterioration. This happens infrequently because most patients are euthanized once they reach the stage of nonambulatory paraparesis or paraplegia.

References

Definitions

Infarct and stroke are synonymous terms used to denote a focal interruption of blood supply to a region of the CNS. In the brain, infarcts are often referred to as lacunar (small, from interruption of small vessel tributaries) or territorial (large, from interruption of a major vessel). They are also described as hemorrhagic or nonhemorrhagic, depending on whether or not there is an associated bleed around the region of vascular disruption. In the spinal cord, most infarcts are due to a disorder called fibrocartilaginous embolic myelopathy (FCE), in which the material causing the infarct has been shown to be identical to nucleus pulposus fibrocartilage.

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).