History
A 1-year-old 23.5-kg mixed-breed wether was presented to the University of Florida Large Animal Hospital for neurologic evaluation and imaging. The sheep was presented 5 months earlier as a rescue from an animal hoarding case to the university hospital for evaluation and management of a mildly comminuted, transverse fracture of the right proximal metatarsus, as well as left hindlimb paresis and stifle laxity. On initial evaluation, the sheep was noted to demonstrate a bilaterally absent menace response and a tendency to turn to the left when stimulated. Further neurologic evaluation was not pursued by the rescue while the fracture and limb laxity were treated. Once obtained by a new owner, further evaluation of the neurologic deficits was elected.
On physical examination, the sheep was bright, alert, and responsive. All vital parameters were within species-accepted limits. Cardiothoracic auscultation was normal, with no adventitious lung sounds, murmurs, or arrhythmias. Abdominal auscultation revealed 2 strong rumen contractions per minute. Rumen stratification palpated normally with no signs of bloat. All externally palpable lymph nodes were within normal limits. The remainder of the physical examination was within normal limits. He was seen ruminating and chewing cud during the examination.
Neurologic evaluation of the patient revealed intermittent circling to the left, an absent menace response in the left eye, and an intermittent menace response in the right eye. Bilateral pupillary light reflexes (direct and consensual) were present but delayed. Bilateral palpebral reflexes were normal. The remainder of the cranial nerve examination was unremarkable. No obvious ataxia or proprioceptive deficits were noted on gait exam. Neuroanatomic localization was consistent with a forebrain lesion.
Complete blood count and serum biochemical analysis were performed. All values were within normal accepted reference ranges. A lumbosacral centesis was performed to collect cerebrospinal fluid, which revealed a WBC count of 1/μL (reference range, 0 to 5/μL), RBC count of 1/μL (reference range, 0 to 2/μL), and total protein of 34.9 mg/dL (reference range, 8 to 70 mg/dL), with no cytologic abnormalities noted.
Based on the suspicion of a forebrain structural lesion, MRI of the brain was performed under general anesthesia (Toshiba Titan 1.5-T unit; Canon Medical Systems Inc). The sheep was positioned in sternal recumbency. Imaging sequences included T2-weighted, FLAIR, T2* weighted gradient echo (GRE), T1-weighted (pre- and postcontrast) transverse plane images; T2W and T1W (pre- and postcontrast) sagittal plane images; and T1W postcontrast dorsal plane images (+/− fat saturation). Postcontrast T1W images were initiated within 3 minutes following intravenous administration of gadolinium-based contrast medium, gadodiamide (Omniscan; GE Healthcare) via manual jugular venous injection. (Figures 1 and 2).
Transverse T2W (A) and FLAIR (B) images of the brain.
Citation: Journal of the American Veterinary Medical Association 260, 11; 10.2460/javma.22.03.0117
Same images as in Figure 1. Transverse plane T2W (A) and FLAIR (B) images of the brain. Severe CSF accumulation within the lateral ventricles is depicted, indicative of hydrocephalus indicated by the asterisks.
Citation: Journal of the American Veterinary Medical Association 260, 11; 10.2460/javma.22.03.0117
Diagnostic Imaging Findings and Interpretation
Magnetic resonance imaging revealed severe dilation of the lateral and third ventricles, causing marked thinning of the surrounding cerebral cortex. At the mid-cranial aspect of the mesencephalic aqueduct, there was focal stenosis (1.2-mm-diameter) (Figures 3 and 4) compared to the caudal aspect (2.4-mm-diameter). The interthalamic adhesion was moderately atrophied and irregularly shaped. On the FLAIR sequence, large, multifocal, incompletely null regions were identified within the ventricles as well as within the globes, bilaterally. There was no evidence of abnormal contrast enhancement. The final diagnosis was severe hydrocephalus, most likely congenital and partially attributed to mesencephalic aqueduct stenosis.
T2W sagittal plane image of the brain, brainstem, and cerebellum.
Citation: Journal of the American Veterinary Medical Association 260, 11; 10.2460/javma.22.03.0117
Same image as Figure 3. T2W sagittal plane. Black arrow designates the focal stenosis of the mesencephalic aqueduct (likely congenital), which was suspected to be an underlying cause of obstructive hydrocephalus in this case. Severe dilation of the lateral ventricles is also seen.
Citation: Journal of the American Veterinary Medical Association 260, 11; 10.2460/javma.22.03.0117
Treatment and Outcome
The owner reported that the sheep demonstrated bruxism and was uncomfortable 48 hours after the MRI. Therefore, he was started on a 7-day course of subcutaneous pantoprazole (1 mg/kg, q 24 h), which resolved these clinical signs. The sheep has remained comfortable since discontinuation of this medication. Ventriculoperitoneal shunts are often performed in small animal and human medicine to shunt CSF away from the brain.1 However, this procedure was not recommended at the time of discharge given the clinically comfortable and stable appearance of the sheep, due to the highly experimental nature of such a procedure in an ovine clinical patient and the high rate of complications associated with these procedures.1
Comments
Magnetic resonance imaging was the key diagnostic tool used to investigate the presumptive forebrain lesion in this patient. Though CT was discussed due to shortened anesthesia time compared to MRI, MRI was chosen for its superior contrast resolution and thus more thorough evaluation of the brain and associated structures. In this case, differential diagnoses prior to MRI included congenital lesions, metabolic diseases (polioencephalomalacia), a space-occupying mass, and traumatic brain injury.
Hydrocephalus is an active distension of the ventricular system of the brain that results from inadequate movement of CSF from the point of production within the ventricles to its point of absorption.2 Congenital hydrocephalus typically occurs because of an interruption of CSF flow or defective CSF absorption. Hydrocephalus can be differentiated into congenital and acquired forms. There are several types of congenital hydrocephalus (internal hydrocephalus, external hydrocephalus, communicating hydrocephalus, and compensatory hydrocephalus) that are characterized based on the location of the CSF accumulation. In this case, there was congenital hydrocephalus caused by a stenosis of the mesencephalic aqueduct restricting CSF flow out of the ventricles.
Congenital hydrocephalus, as was presumed in this case, is reported intermittently in lambs and sheep and may be caused by genetic or environmental factors. Affected animals often are stillborn or die shortly after birth. Cases of congenital hydrocephalus have been reported in a Comasina sheep and in lambs exposed to viral (Bluetongue, Akabane, Cache Valley, Border disease, and Schmallenberg) etiologies in utero3 but otherwise the condition and its long-term prognosis is underreported. In this case, geographic location would make bluetongue virus infection the only potential viral etiology. Further investigation of bluetongue virus as the cause of this sheep’s congenital hydrocephalus was not pursued. In this patient, congenital mesencephalic aqueduct stenosis was suspected to be an underlying or contributing cause of hydrocephalus. Mesencephalic aqueduct stenosis has been previously documented as a cause of congenital hydrocephalus in small animals, but this is the first case, to the authors’ knowledge, of this phenomenon occurring in sheep. Congenital hydrocephalus is also reported in the human literature, where sheep are used as models of hydrocephalus for the development of interventions in human medicine, with a variety of models of inducing hydrocephalus reported.4
This case highlights the importance of the use of advanced diagnostic imaging when localizing lesions to the forebrain. The use of MRI in this case not only helped to ascertain a diagnosis but also helped to direct treatment and prognosis of the patient by ruling out a space-occupying mass or trauma as the cause of the sheep’s clinical signs. MRI additionally helped to confirm the congenital cause of the hydrocephalus (stenotic mesencephalic aqueduct) found in this sheep. The diagnosis of hydrocephalus helped to guide clinical treatment when the patient experienced presumed adverse effects of this disease process. Omeprazole has been documented to reduce CSF production in small animals and humans.5 Pantoprazole was used instead in this case due to concerns regarding the oral bioavailability of omeprazole in a ruminant. Dogs and cats with congenital hydrocephalus may have signs from birth; however, it is more common for signs to become apparent in the first few months of life. The recent history of rescue in the sheep of this report makes a clear timeline of clinical signs difficult to ascertain; however, during the 5 months of follow-up at our hospital, his neurologic abnormalities appeared to improve mildly, with a reduction in frequency of circling to the left. The rate of clinical progression of congenital hydrocephalus is variable, and some animals may not develop clinical signs of encephalopathy until adulthood.5 In this case, the owner was given a good short-term prognosis and guarded long-term prognosis, based on literature in dogs and cats, as well as a perceived improvement of clinical signs which can be presumptively attributed to improving orthopedic status and learned compensation for neurologic deficits.
References
- 1. ↑
Johnston MG, Del Bigio MR, Drake JM, Armstrong D, Di Curzio DL, Bertrand J. Pre- and post-shunting observations in adult sheep with kaolin-induced hydrocephalus. Fluids Barriers CNS. 2013;10:24. doi:10.1186/2045-8118-10-24
- 2. ↑
Varela MF, Miyabe MM, Oria M. Fetal brain damage in congenital hydrocephalus. Childs Nerv Syst. 2020;36(8):1661–1668. doi:10.1007/s00381-020-04657-9
- 3. ↑
Edwards JF, Livingston CW, Chung SI, Collisson EC. Ovine arthrogryposis and central nervous system malformations associated with in utero Cache Valley virus infection: spontaneous disease. Vet Pathol. 1989;26(1):33–39. doi:10.1177/030098588902600106
- 4. ↑
Emery SP, Greene S, Murdoch G, Wiley CA. Histologic appearance of iatrogenic obstructive hydrocephalus in the fetal lamb model. Fetal Diagn Ther. 2020;47(1):7–14. doi:10.1159/000497360
