Neurology

History and clinical signs

A 4.5-year-old, male neutered Chihuahua-cross dog was referred to the ophthalmology service of Western Veterinary Specialist and Emergency Centre with a history of acute onset of disorientation with intermittent episodes of impaired vision and right-sided head tilt over the past 3 d. The owners reported that the dog appeared completely blind in the left eye with limited vision from the right eye. The dog was lethargic, listless and had a diminished appetite 2 d prior to the onset of his vision problems. He was receiving oral meloxicam, 0.08 mg/kg, PO, q24h of 8 mo duration for back pain and arthritis. Neuro-ophthalmic examination revealed absence of a menace response of the left eye, and of the medial visual field of the right eye and a positive menace response from the lateral visual field of the right eye. The dog’s pupils were equal in size and were of normal size in both ambient light and scotopic conditions. Direct and consensual (indirect) pupillary light reflexes (PLRs) and dazzle reflexes were normal from both eyes. Ocular diagnostic testing (Color Bar Schirmer Tear Test Standardized Sterile Strips; EagleVision, Memphis, Tennessee, USA) revealed values were 20 mm/min from the right eye and 21 mm/min from the left eye. Following instillation of 1 drop of topical 0.5% proparacaine (Alcaine; Alcon Canada, Mississauga, Ontario) on each eye, applanation tonometry (Tono-Pen Vet; Medtronic Ophthalmics, Jacksonville, Florida, USA) was performed and revealed intraocular pressures (IOPS) of 14 mmHg in the right eye and 11 mmHg in the left eye [mean +/− standard deviation (s); normal IOP = 19.2 ± 5.9 mmHg (1)]. Neither cornea retained fluorescein stain (Fluorets Fluorescein Sodium Ophthalmic Strips USP; Bausch & Lomb Canada, Vaughan, Ontario). Transilluminator and slit lamp biomicroscopic (Kowa SL-15; Kowa, Tokyo, Japan) examinations revealed mild medioventral entropion bilaterally. Indirect ophthalmoscopy (Heine Omega 500 Binocular Indirect Ophthalmoscope; Heine Instruments, Kitchener, Ontario), following pupillary dilation using topical 1% tropicamide (Mydriacyl; Alcon Canada, Mississauga, Ontario), failed to identify any abnormalities. A maze test revealed that the dog failed to navigate through the obstacle course in both bright light (photopic) and dim light (scotopic) conditions. In particular, the dog was observed to move tentatively and bumped into objects while in the obstacle course and while walking in the clinic.

Physical and neurologic examinations were unremarkable with the exception of the aforementioned deficits in the menace response. Although significant changes in demeanour were reported in the 2 d prior to presentation (listlessness and lethargy), no obvious changes, other than the aforementioned vision deficits, were noted during the neurological examination possibly due to the overstimulation and excitement often observed in dogs in an unfamiliar environment. In particular, no other cranial nerve deficits were detected and no significant changes were noted on examination of the gait and posture, postural reactions and spinal reflexes.

Where is the neuroanatomic lesion localization for this dog’s vision loss, and what are your plans for further diagnostic work-up?

Discussion

Based on the history of listlessness and lethargy, bumping into objects and moving tentatively, along with the abnormality in the menace response, appropriately sized pupils, and normal direct and indirect PLRs in both eyes, the lesion was localized to the right thalamocortex involving likely the right visual cortex (right-sided cortical blindness). The presence of a dazzle reflex from each eye, a subcortical reflex that does not require an intact cerebral cortex, further supported cortical blindness.

In order to explain the abnormalities detected on the right eye, a brief discussion of the neuroanatomical structures involved in this pathway will be discussed and illustrated.

In the dog, decussation at the level of the optic chiasm of the optic nerve fibers originating from the medial portion of the retina accounts for approximately 75% of these fibers. The remaining optic nerve fibers, originating from the lateral/ temporal aspect of the retina, tend to remain on the side ipsilateral to the eye. When performing the “menace response” gesture, it is important to cover the eye not being tested and to menace the other eye from both its medial and lateral sides. The deficit will be more pronounced from the lateral side (visual field) when there are contralateral lesions in the central visual pathway. The dog in this case had an absent menace response from the left eye (from both medial and lateral visual fields) suggesting a contralateral lesion in the right visual cortex. When the right lateral visual field was stimulated (when a menacing hand gesture was performed from the lateral aspect of the right eye, thereby stimulating the medial aspect of the retina), a blink was generated, suggesting integrity of the left visual cortex (right medial retina → optic nerve fibers decussate → left cerebral cortex; Figure 1). However, when the right medial visual field was stimulated (when a menacing hand gesture was performed from the medial aspect of the right eye, thereby stimulating the lateral aspect of the retina), no blinking response was generated, suggesting an ipsilateral lesion affecting the right cerebral cortex (visual cortex).

Figure 1.

Diagram illustrating the canine afferent portion of the menace response [visual pathway (blue and grey)] and the efferent neural pathways making up the menace response (green and purple). It is important to note that the menace response is a learned response and not a reflex. Note the pattern of decussation of the optic nerve fibers at the level of the optic chiasm.

We advised further diagnostic work-up in the forms of an electroretinogram (ERG) to evaluate retinal function to completely rule-out the possibility of sudden acquired retinal degeneration syndrome (SARDS), and blood-work [complete blood cell count (CBC); biochemistry profile] and urinalysis to evaluate metabolic and other systemic causes of cortical blindness including hypoglycemia, hepatic encephalopathy, and uremic encephalopathy. The ERG revealed an a-wave and a b-wave for both eyes confirming the presence of retinal function, and eliminating the possibility of SARDS. The CBC was unremarkable. The biochemistry profile revealed mild elevations in serum alkaline phosphatase (ALP = 155 U/L; normal range: 20 to 150 U/L), alanine transaminase (ALT = 162 U/L; normal range: 10 to 118 U/L) and glucose (glucose = 7.1 mmol/L; normal range: 3.3 to 6.1 mmol/L), and hypophosphatemia (phosphorus = 0.7 mmol/L; normal range: 0.93 to 2.13 mmol/L). Urinalysis revealed a urine specific gravity of 1.047 with trace protein. The elevations in the hepatic enzymes were considered mild. Magnetic resonance (MR) imaging of the brain and a cerebrospinal fluid (CSF) collection were advised, and were performed to help determine the cause of the suspected right cerebrocortical lesion. MR imaging revealed a large peripheral zone of abnormal cerebral cortex of the right cerebral hemisphere that extended from the level adjacent to the level of the lateral ventricular system caudally to the supratentorial region (the region of the brain located rostral to the tentorium cerebelli) (2). The abnormal signal was hyperintense compared to surrounding brain tissue on both fluid-attenuated inversion recovery (FLAIR) and T2-weighted imaging (Figure 2). There was no mass effect associated with the abnormal signal (for example, no evidence of midline shift). Both white and gray matter were involved. The pre-contrast T1-weighted imaging revealed that this region was hypointense relative to normal white and gray matter with slight hyperintense inner margination. Contrast enhancement images showed enhancement of both the white and gray matter with meningeal enhancement within the sulci and gyri of this region. The optic nerves, remainder of the brain parenchyma, brainstem, and cerebellum appeared normal. The pattern of lesion distribution was supportive of a large vascular insult, most likely an infarct with associated inflammation and edema. Other possible causes included infectious or inflammatory encephalopathy. A CSF analysis revealed no evidence of infectious agents or cytological abnormalities; hence, a diagnosis of right-sided cerebrocortical infarct was made.

Figure 2.

Fluid-attenuated inversion recovery (FLAIR) axial MR image demonstrating an abnormal hyperintense signal in the right caudal half of the occipital lobe (*; area of the primary visual cortex) compared to the surrounding brain tissue. There is no mass effect associated with the abnormal signal (for example, no evidence of midline shift). Both white and gray matter are involved.

An infarct is an area of dead tissue resulting from reduced oxygen supply. In the brain, infarcts occur due to an ischemic event secondary to a local vascular obstruction (thrombus) or a vascular obstruction transported to the brain from a site elsewhere in the body (thromboembolism) (3,4). Cerebrovascular disease is the term used to describe an abnormality of the brain that arises due to a pathologic process affecting its blood supply (3,4). Stroke or cerebrovascular accident (CVA) is the clinical manifestation of cerebrovascular disease. A CVA is characterized by an acute onset of nonprogressive focal signs of brain dysfunction secondary to cerebrovascular disease (3,4). There are 2 main types of CVAs: 1) ischemic stroke (with or without infarction) caused by occlusion of the lumen of a vessel by a thrombus or an embolus, and 2) hemorrhagic stroke caused by rupture of a blood vessel wall (5). During a CVA, if adequate cerebral perfusion pressure is not rapidly re-established in the brain, delivery of glucose and oxygen is compromised when cerebral perfusion pressure falls below threshold value resulting in subsequent ischemia which progresses to necrosis of neurons and glial elements (infarction) (3,4).

In the present case, ischemic stroke with infarction was diagnosed, based upon the acute and nonprogressive neurological signs, ophthalmic findings, MR imaging findings, lack of abnormalities in CSF, and other clinicopathological findings. In humans, ischemic strokes and infarction can be classified based on: 1) the vascular territory involved, 2) the size of the affected vessels, 3) the suspected underlying etiology, and 4) the numbers of red blood cells that are detected in the necrotic tissue dividing infarcts into pallid (pale infarct) or hemorrhagic (red infarct) (3). Strokes have been previously reported to be uncommon in small animals with the true prevalence of strokes in dogs being unknown. Recently, strokes are being recognized with increased frequency in veterinary medicine with the advent of increased accessibility of MR imaging (3,4,6–9). As well, new functional MR imaging sequences used commonly in humans such as diffusion-weighted imaging (DWI) have increased the sensitivity and specificity for the diagnosis of acute stroke compared with those of conventional MR imaging (3,10).

The specific neurologic deficit linked with brain infarction depends on the size and location of the infarct. Brain infarction may be associated with disease affecting large-diameter blood vessels or small intraparenchymal, penetrating arteries causing territorial (larger) and lacunar (smaller) infarcts, respectively. In this case, a right-sided supratentorial infarct was observed within the territory of the middle cerebral artery (11). In humans, the territory of the middle cerebral artery is one of the most common locations for territorial infarcts [cited in (3)]. A recent retrospective study reviewing the medical records of 40 dogs diagnosed with suspected brain infarction using MR imaging revealed territorial infarcts in half of the dogs with the most common location being the cerebellum within the territory of the rostral cerebellar artery (3).

Histopathologically identified and confirmed suspected causes of brain infarction in dogs include septic thromboemboli (12), atherosclerosis associated with primary hypothyroidism (13–15), hyperadrenocorticism (13), embolic metastatic neoplastic cells (13), parasitic (Dirofilaria immitis) emboli or migration (16), chronic renal disease (13), intravascular lymphoma (17), and fibrocartilaginous embolism (18). A recent retrospective study reported detection of a concurrent systemic condition in 18/33 dogs with brain infarcts, with chronic renal disease (8/33) and hyperadrenocorticism (6/33) being most commonly encountered (4). Additional systemic work-up of the dog in this case was advised to help determine the cause of the brain infarction. In particular, systemic blood pressure measurements, CBC, biochemistry profile including cholesterol and triglycerides, and a urine protein/creatinine ratio were performed. Multiple blood pressure measurements were taken via indirect (Doppler) measurement throughout the day while the dog was hospitalized, and there was no evidence of systemic hypertension with a mean systolic blood pressure reading of 123 mmHg. The CBC revealed mild neutrophilia (14.53 × 10⁹/L; normal range: 3.0–10 × 10⁹/L), mild lymphopenia (0.67 × 10⁹/L; normal range: 1.2 to 5.0 × 10⁹/L) and mild monocytosis (1.17 × 10⁹/L; normal range: 0.08 to 1.0 × 10⁹/L) consistent with a stress leukogram. The biochemistry profile was repeated to help establish a trend in the hepatic enzyme elevations detected on initial screening. The mild elevations in ALP and ALT persisted but had not worsened. The serum cholesterol and triglycerides, and urine protein-to-creatinine ratio were normal. Given the dog’s currently stable systemic status and nonprogressive neurological signs, the owner opted not to pursue further diagnostic work-up.

This case illustrates the importance of a thorough neurologic examination, including neuro-ophthalmic examination, in localizing blindness-associated lesions. In particular, the presence of the PLRs and dazzle reflex of both eyes (subcortical reflexes), and pupils of normal size in both eyes were key findings that supported cortical blindness.