A 13-year-old 6.3-kg (13.9-lb) spayed female Norwich Terrier was evaluated because of a 1-week history of progressive neurologic signs characterized by balance upset, circling, listlessness, and episodic head twitching. The dog had fallen into the owners' pool (neurologic signs had preceded this event). The dog had cutaneous indolent T-zone lymphoma with regional lymph node metastasis, which was managed with prednisone and chlorambucil and was reportedly static (8 months following diagnosis). Prednisone treatment had been discontinued 6 days prior to the evaluation. The dog had bilateral iris atrophy, a grade 2/6 systolic heart murmur, bilateral grade III/IV medial patellar luxation, and mild prescapular and popliteal lymph node enlargement. Neurologic examination revealed bright mentation, mild left head tilt, propulsive pacing gait (circling left), bilaterally enlarged pupils with reduced to absent pupillary light reflexes (attributed at the time to iris atrophy), and a few beats of slow vertical nystagmus when the dog was in right lateral recumbency. Postural reactions were delayed on the left side only. Pelvic limb reflexes were increased bilaterally, but muscle tone was subjectively normal in all 4 limbs.
What is the problem? Where is the lesion? What are the most probable causes of this problem? What is your plan to establish a diagnosis? Please turn the page.
Assessment
Anatomic diagnosis
| Problem | Rule out location |
|---|---|
| Propulsive pacing and circling left | Prosencephalon (left side more likely than right side) |
| Bilateral mydriasis with reduced to absent pupillary light reflexes (normal menace responses) | Iris sphincter, bilateral oculomotor nerve, Edinger-Westphal nuclei, or pretectal nuclei |
| Left head tilt (subtle), positional vertical nystagmus, and difficulty with gaze adjustment | Caudal fossa (vestibular nuclei of medulla and cerebellum), left cranial nerve VIII, or vestibular-sensitive areas of thalamus and parieto-insular cerebral cortex |
| Delayed hopping on the left side (thoracic and pelvic limbs) | Right-sided prosencephalon, left-sided caudal fossa, or left-sided C1-C5 region |
| Increased reflexes in the pelvic limbs | T3-L3 myelopathy |
Likely location of 1 lesion
| A single right-sided thalamic lesion was considered versus multifocal or diffuse brain disease. An underlying T3-L3 myelopathy was also considered as a cause of the increased pelvic limb reflexes. |
Etiologic diagnosis—Differential diagnoses considered for a lesion causing progressive central vestibular and prosencephalic signs included neoplasia, an infectious or inflammatory disease process, or a degenerative disease. Given the dog's history of lymphoma, neoplasia was considered far more likely than alternative differential diagnoses. Vascular disease was considered possible but unlikely because of the dog's progressive signs. The initial diagnostic plan included a CBC, serum biochemical analysis, and noninvasive blood pressure measurement. Assessment of all thyroid hormone concentrations was recommended but not performed. A 3-view thoracic radiographic series was obtained by the referring veterinarian 2 days prior to the evaluation. The dog had undergone abdominal ultrasonography 8 months prior to the evaluation at the time of diagnosis of cutaneous lymphoma; repeated ultrasonographic examination was considered but not performed. Magnetic resonance imaging of the brain and CSF sample analysis were planned to follow the initial preanesthetic diagnostic investigation.
Diagnostic test findings—The CBC revealed no notable abnormalities. The serum biochemical analysis revealed mildly high total protein concentration consistent with hemoconcentration. Results of noninvasive blood pressure measurement were normal. On the thoracic radiographic views obtained at the referring hospital, there was a progressive diffuse bronchial pattern and underlying mild interstitial pattern compared with radiographic findings from 8 months prior. A radiographic diagnosis of bronchitis was made.
The dog was anesthetized, and MRI of the head was performed with a 1.5-T scanner.a Sagittal (T2-weighted), transverse (T2-weighted, fluid-attenuated inversion recovery [FLAIR], T1-weighted, T1-weighted with contrast agentb administration, T2*-weighted gradient echo, diffusion-weighted imaging, and apparent diffusion coefficient), and dorsal (T1-weighted and T1-weighted with contrast agentb administration) plane images of the brain were obtained for review.
A T2-weighted hyperintense, T1-weighted hypointense intra-axial mass was found in the region of the right brainstem (Figure 1). A very mild amount of peripheral contrast enhancement was seen around the mass on T1-weighted images following IV administration of contrast agent.b The mass was hyperintense on diffusion-weighted imaging and isointense on the apparent diffusion coefficient images. The mass caused a mild leftward midline shift; it extended from the level of the interthalamic adhesion rostrally to the level of the caudal colliculus caudally. The T2-weighted hyperintensity included the following major anatomic structures on the right side: the ventral thalamic nuclei, the medial geniculate nucleus (and to a lesser extent, the lateral geniculate nucleus), and the rostral and caudal colliculi. Multiple punctate T2*-weighted gradient echo signal voids were seen throughout the cerebral white matter and bilaterally within the caudate nuclei; these were consistent with prior small hemorrhagic infarctions, although a neoplastic cause was not completely excluded.1 Moderate leukoaraiosis was also present on the FLAIR images. These lesions were considered to be incidental and unrelated to the dog's clinical signs. No abnormalities of either middle ear or the regions in the caudal fossa containing the vestibular nuclei were identified. A sample of CSF was collected from the cerebellomedullary cistern. Microscopic examination of the sample revealed no cytologic abnormalities (0 nucleated cells/μL, 0 RBCs/μL, and 24 mg of protein/dL).
T2-weighted MR images obtained from a 13-year-old dog that was evaluated because of progressive neurologic signs characterized by balance upset, circling, listlessness, and episodic head twitching of 1 week's duration. A—In the right parasagittal image, the lines indicate the location at which the corresponding axial images (B through D) were obtained. A hyperintense intra-axial mass is present in the region of the right brainstem. B—The rostral aspect of the mass lesion predominantly involves the ventral thalamic nuclei. C—At the level of medial and lateral geniculate nuclei, there is some hyperintensity associated with the hippocampus. D—The caudal extent of the mass primarily involves the caudal colliculus and its associated brachium.
Citation: Journal of the American Veterinary Medical Association 253, 11; 10.2460/javma.253.11.1409
T2-weighted MR images obtained from a 13-year-old dog that was evaluated because of progressive neurologic signs characterized by balance upset, circling, listlessness, and episodic head twitching of 1 week's duration. A—In the right parasagittal image, the lines indicate the location at which the corresponding axial images (B through D) were obtained. A hyperintense intra-axial mass is present in the region of the right brainstem. B—The rostral aspect of the mass lesion predominantly involves the ventral thalamic nuclei. C—At the level of medial and lateral geniculate nuclei, there is some hyperintensity associated with the hippocampus. D—The caudal extent of the mass primarily involves the caudal colliculus and its associated brachium.
Citation: Journal of the American Veterinary Medical Association 253, 11; 10.2460/javma.253.11.1409
T2-weighted MR images obtained from a 13-year-old dog that was evaluated because of progressive neurologic signs characterized by balance upset, circling, listlessness, and episodic head twitching of 1 week's duration. A—In the right parasagittal image, the lines indicate the location at which the corresponding axial images (B through D) were obtained. A hyperintense intra-axial mass is present in the region of the right brainstem. B—The rostral aspect of the mass lesion predominantly involves the ventral thalamic nuclei. C—At the level of medial and lateral geniculate nuclei, there is some hyperintensity associated with the hippocampus. D—The caudal extent of the mass primarily involves the caudal colliculus and its associated brachium.
Citation: Journal of the American Veterinary Medical Association 253, 11; 10.2460/javma.253.11.1409
Despite the dog's prior history of lymphoma, MRI signal characteristics and lack of CSF abnormalities were more consistent with a primary brain neoplasm, such as a glioma. Thalamic infarction was not completely excluded, although the distribution of change was inconsistent with previously described thalamic infarcts and the described progression of signs made a vascular cause less likely from a clinical standpoint.
Following tentative diagnosis of the intra-axial neoplasm, the dog was restarted on an anti-inflammatory dose of prednisone (0.8 mg/kg [0.3 mg/lb], PO, q 24 h). Treatment with phenobarbital (2.4 mg/kg [1.1 mg/lb], PO, q 12 h) was also started because of concerns that the described head tremor and twitching episodes represented focal seizure activity. Radiation therapy was recommended but not pursued by the owners. The dog was given a poor long-term prognosis. The owners reported progressive deterioration in mentation and development of a pleurothotonus (right or left head turn not specified) in the days following the dog's discharge from the hospital and opted for euthanasia 4 days following diagnosis. The dog did not undergo a necropsy.
Comments
The mass lesion in the dog of the present report was interesting in that it was almost exclusively confined to the right side of the thalamus. As a 2-way relay station between the cerebral cortex and the rest of the CNS, the thalamus has an integral role in the most basic (ie, maintenance of consciousness) to the more refined (ie, cerebral integration of polysensory data) tasks of the CNS.2 Accordingly, thalamic lesions may cause a wide range of neurologic deficits.
For the dog of the present report, most if not all the neurologic deficits could be ascribed to changes related to a thalamic lesion. Contralateral proprioceptive deficits are common with unilateral prosencephalic lesions. With regard to the thalamus, contralateral postural deficits should be expected with lesions involving the ventrolateral nucleus or associated cortical projections.2 Propulsive pacing and circling are also common with a prosencephalic lesion. When a patient circles toward the same side as its proprioceptive deficits and the neurolocalization is the prosencephalon, one should carefully review the postural reaction deficits to determine the laterality of the lesion because circling and head aversion are unreliable indicators of laterality in the face of prosencephalic signs.2 For this reason, a right-sided prosencephalic lesion was suspected for the dog of the present report, despite the fact that its observed circling was to the left.
Interestingly, this dog also had subtle vestibular signs including a mild left head tilt, slow positional nystagmus, and superfluous saccadic eye movement during adjustment of gaze. Convention describes the vestibular system as limited to the vestibular organs of the inner ear, the vestibular nerve, and corresponding vestibular nuclei in the medulla and cerebellum.3 However, an extensive thalamocortical vestibular system interfaces with the vestibular nuclei of the caudal fossa.4 Vestibular disease is reported in cases of thalamic infarction, and head tilting to the side contralateral to the lesion is common in the event of infarction involving the caudal perforating arteries and paramedian branches of the caudal cerebral artery.5 In the case described in the present report, a right-sided thalamic lesion was thought to be associated with a left-sided head tilt. Although MRI findings indicated no evidence of structural disease affecting the caudal fossa, an undetectable vascular event in this region (given the evidence of previous multifocal hemorrhagic infarcts) or idiopathic vestibular disease were alternative explanations for the concurrent vestibular signs identified on examination. Dogs with putative cerebral microbleeds are known to be at increased risk of development of vestibular dysfunction, although a causal relationship between putative cerebral microbleeds and vestibular signs has not been established.6 Postmortem examination is lacking in this case, but the tentative diagnosis of neoplasia is at odds with previous notions that only peracute thalamic disease (ie, infarction) should result in vestibular upset.7
For the dog of the present report, the head twitching episodes described by the owners (but not witnessed by hospital staff) were suspected to be partial seizure activity given the location of the lesion. For this reason, phenobarbital initiation was recommended. It is unclear to what extent the phenobarbital contributed to the owners' perceived decline in the patient's mentation in the days following discharge from the hospital. With that said, the development of pleurothotonus would not be consistent with initiation of phenobarbital treatment alone and was more concerning for progression of disease.
Other signs associated with thalamic lesions in animals that are frequently reported include contralateral hemianopsia or hemianesthesia, pupillary light reflex deficits, and reduced consciousness.2 The fact that the lateral geniculate nucleus appeared to be relatively spared in the case described in the present report may account for the absence of an appreciable menace response or visual deficit on examination; however, the owners did report that the dog appeared to not see the swimming pool at its left side before falling in and that it normally kept a large distance from the pool. The dog's bright mentation at the time of diagnosis may also be explained by the fact that the lesion did not appear to affect the central or intralaminar thalamic nuclei, the final relay in the ascending reticular activating system.2
The diversity of neurologic signs in the dog of the present report has highlighted the fundamental role of the thalamus in CNS functioning. A thalamic lesion should be considered as an alternative diagnosis to multifocal brain disease processes in cases wherein vestibular problems accompany primarily prosencephalic signs.
Footnotes
GE LX 1.5 Tesla MR scanner, GE Healthcare, Milwaukee, Wis.
Magnevist (gandopentate dimeglumine), Bayer HealthCare Pharmaceuticals, Wayne, NJ.
References
1. Fulkerson CV, Young BD, Jackson ND, et al. MRI characteristics of cerebral microbleeds in four dogs. Vet Radiol Ultrasound 2012;53:389–393.
2. King AS. Physiological and clinical anatomy of the domestic mammals. Vol. 1: Central nervous system. New York: Oxford University Press, 1987.
3. DeLahunta A, Glass E. Chapter 12: Vestibular system: special proprioception. In: Veterinary neuroanatomy and clinical neurology. 3rd ed. St Louis: Elsevier, 2009;319–328.
4. Lopez C, Blanke O. The thalamocortical vestibular system in animals and humans. Brain Res Rev 2011;67:119–146.
5. Gonçalves R, Carrera I, Garosi L, et al. Clinical and topographic magnetic resonance imaging characteristics of suspected thalamic infarcts in 16 dogs. Vet J 2011;188:39–43.
6. Kerwin SC, Levine JM, Budke CM, et al. Putative cerebral microbleeds in dogs undergoing magnetic resonance imaging of the head: a retrospective study of demographics, clinical associations, and relationship to case outcome. J Vet Intern Med 2017;31:1140–1148.
7. Dewey CW, da Costa RC. Chapter 7: Encephalopathies. In: Practical guide to canine and feline neurology. 3rd ed. Ames, Iowa: Wiley-Blackwell, 2015;212–213.
