History
An 11-month-old spayed female Labrador Retriever was presented for a 2-month history of nonprogressive right-side circling, right head tilt, and right facial paresis along with intermittent episodes of closed-mouth panting. The level of activity at home was considered normal. Prior to presentation, the dog had received 1 month of clindamycin (13 mg/kg, q 12 h) for suspicion of right otitis media/interna by the primary care veterinarian, with no clinical improvement. The patient was referred for further investigations.
Upon presentation, the dog showed an atypical, closed-mouth panting respiratory pattern with tachypnea (180 breaths/min) and hyperpnea. The remainder of the physical examination was unremarkable. On neurological examination, the dog was quiet but alert and responsive. The dog was ambulatory with a strong tendency to circle to the right. Mild proprioceptive ataxia of the pelvic limbs was noted. Cranial nerve examination findings included a right facial nerve paresis characterized by right ptosis and right lip contraction, right-sided head tilt, ventral positional strabismus of the right eye and right eye retinal vessel rotation, evident on fundoscopic examination. Postural reactions and spinal reflexes were unremarkable. The remainder of the neurologic examination was within reference limits. Neuroanatomic localization was consistent with right brainstem (ie, nuclei of right cranial nerves IV, VII, and VIII and potentially the pontine respiratory groups) and right thalamo-cortex, with involvement of the latter explaining the right-sided circling.
Results of a CBC and serum biochemical analyses were within reference range. Blood testing for tick-borne diseases was negative. Arterial blood gas analysis revealed a mild respiratory alkalosis (pH, 7.556 [reference range, 7.35 to 7.45]; PCO2, 26.0 mmHg [reference range, 34 to 40 mm Hg]; HCO3–, 23 mmol/L [reference range, 20 to 24 mmol/L]; Cl–, 108 mmol/L [reference range, 106 to 127 mmol/L]).
MRI (1.5-T Signa Excite; General Electric Medical Systems) of the brain was performed with the dog under general anesthesia using a knee coil (Figure 1). MRI sequence acquisition included T2-weighted (T2W) fast spin echo, T2W fluid-attenuated inversion recovery (FLAIR), pre– and post–contrast administration T1W FLAIR, T2* gradient recalled echo, single-shot fast spin echo, and diffusion-weighted imaging with the addition of apparent diffusion coefficient and exponential apparent diffusion coefficient maps. Transverse T1W FLAIR images were acquired before (T0) and at 5 (T5), 10 (T10), and 15 minutes (T15) following gadolinium administration, applying fat saturation to the sequence acquired at T10. Sagittal and dorsal plane T1W FLAIR images were obtained following acquisition of transverse images at T0 and T15, respectively. Next, CSF was collected from the cerebello-medullary cistern. White blood cell count (0 cells/µL; reference range, < 3 cells/µL) and CSF proteins (0.14 g/L; reference range, < 0.25 g/L) were within reference range values.
Transverse T2-weighted (T2W; A), T2W fluid-attenuated inversion recovery (FLAIR); B), T1W FLAIR precontrast (C), and T1W FLAIR postcontrast (D) MRI images at the level of the mesencephalic aqueduct of an 11-month-old female spayed Labrador Retriever evaluated for circling to the right side, right head tilt, right facial paresis, and episodes of closed-mouth panting.
Citation: Journal of the American Veterinary Medical Association 261, 2; 10.2460/javma.22.08.0362
Diagnostic Imaging Findings and Interpretation
An ill-defined lesion extended from the mid aspect of the right thalamus and right subthalamus to the ipsilateral pons and rostral cerebellar peduncle, encompassing the right midbrain tegmentum. The intra-axial portion of the lesion was heterogeneously hyperintense to the contralateral parenchyma on T2W sequences without signal suppression on FLAIR, compatible with edema or gliosis. The periaqueductal gray matter located ventrolateral to the mesencephalic aqueduct is hyperintense (R > L). The lesion was also faintly hypointense compared with the contralateral parenchyma on precontrast T1W FLAIR images. No mass effect was observed. Postcontrast T1W FLAIR images revealed focal meningeal contrast enhancement along the right lateral margins of the midbrain, extending slightly into the adjacent nervous tissue and dorsorostral margins of the pons, sparing the cortical and cerebellar parenchyma (Figure 2). Enhancement was most intense at T5, progressively decreasing in intensity and edge sharpness at T10 and T15. The right mandibular lymph nodes were slightly increased in size compared with the contralateral side. The remaining structures on MRI were within reference limits. MRI findings were compatible with a meningo-encephalitis of infectious or immune-mediated causes. However, CSF analysis was not in favor of inflammation. Other differentials included a round cell tumor or a meningeal malformation such as meningioangiomatosis. A primary intracranial neoplasia was considered less likely since meningeal involvement is uncommon with intra-axial tumors, and the absence of a mass effect in the presence of intra-axial extension of the lesion was also not consistent with extra-axial tumors.
Same MRI images as in Figure 1. An intra-axial lesion, heterogeneously hyperintense on T2W sequences compared with the surrounding parenchyma and with ill-defined margins, not suppressing on T2W FLAIR, and faintly hypointense on T1W FLAIR images, is present in the right mesencephalon (arrows). The lesion extends to the periaqueductal gray matter, which is hyperintense (R > L). Meningeal enhancement with slight parenchymal enhancement is noted after contrast administration (arrowhead). Note the absence of a mass effect on the surrounding structures including left mesencephalon. L = Left.
Citation: Journal of the American Veterinary Medical Association 261, 2; 10.2460/javma.22.08.0362
Treatment and Outcome
Cytology of the right mandibular lymph node revealed a nonspecific reactive lymphoid hyperplasia. Biopsy could not be performed due to the anatomic localization of the lesion. Based on a presumptive diagnosis of meningo-encephalitis, a course of clindamycin (13 mg/kg, PO, q 12 h) and prednisone (1.5 mg/kg, PO, q 24 h) was initiated. After 2 weeks of treatment, clinical signs worsened. A course of trimethoprim-sulfamethoxazole (15 mg/kg, PO, q 12 h) and doxycycline (5 mg/kg, PO, q 12 h every 12h) were instated, without subsequent clinical improvement. Immunosuppressive drug therapy was attempted with cytosine arabinoside injections at a 3-week interval (275 mg/m2 divided in 4 SC injections, q 2 h), followed by azathioprine (2.25 mg/kg, PO, q 24 h). Episodes of closed-mouth breathing initially decreased in frequency after the first round of cytosine arabinoside injections, but not following the second round. Five months following the initial presentation, neurological deficits had worsened with increased right-sided circling and more frequent episodes of closed-mouth breathing. Owners elected for humane euthanasia and consented to a necropsy. On gross examination, the right side of the brainstem showed an irregular grayish discoloration over approximately 3 X 1 X 1 cm. The changes extended minimally to the left side in a few brainstem sections. Adjacent leptomeninges had a gray-black coloration multifocally. Histopathologic examination revealed thickening of the leptomeninges by loose cords of bland fusiform cells supported by a fibrous stroma expanding into the underlying neuroparenchyma via the Virchow Robin spaces. These lesions were centered on several blood vessels, mainly arterioles (Figure 3 and 4). These findings are consistent with meningioangiomatosis, a rare benign proliferative disorder of the meninges and underlying neuroparenchyma.
Photomicrograph of the right side of the brainstem stained with hematoxylin eosin phloxine saffron. Leptomeninges are thickened by an ill-defined, mildly cellular process that dissects into the leptomeninges and extends into the underlying neuroparenchyma via the Virchow Robin spaces. Histopathological changes are characterized by loose anastomosed cords of bland fusiform cells supported by fibrous tissue and centered on several blood vessels, especially arterioles. These changes are consistent with meningioangiomatosis. Note that freezing artifacts are present on the section. Bar = 600 µm.
Citation: Journal of the American Veterinary Medical Association 261, 2; 10.2460/javma.22.08.0362
Closer magnification of Figure 3 stained with hematoxylin eosin phloxine saffron. Note that freezing artifacts are present on the section. Bar = 300 µm.
Citation: Journal of the American Veterinary Medical Association 261, 2; 10.2460/javma.22.08.0362
Comments
Meningioangiomatosis is a rare proliferative disorder of the CNS that remains of uncertain etiology. The few reports1–4 of this condition in dogs have described a leptomeningeal plaque of proliferating cells extending from the subarachnoid space along the perivascular spaces into the adjacent parenchyma. Young dogs are more frequently affected than older dogs, a demographic feature shared with humans, among whom children and young adults are more likely to develop meningioangiomatosis.1,3,5 While meningioangiomatosis mainly affects the cerebral cortex in humans, a variety of localization has been reported in dogs, including cerebrum, brainstem, spinal cord, and cerebellum.1,2,5
Definitive diagnosis of meningioangiomatosis relies on histopathology through surgical excision. However, lesion biopsy may be limited in inaccessible brain regions. Since clinical signs overlap with other conditions, antemortem diagnosis relies heavily on advanced imaging such as CT or MRI in both dogs and humans.3,5 There are no pathognomonic MRI features of meningioangiomatosis in humans. The most commonly reported lesions in humans with meningioangiomatosis include T1W hypointensity and heterogenous hyper- and hypointense signal on T2W sequences of the brain parenchyma. Contrast enhancement is also commonly described with meningioangiomatosis, especially in the meninges, along with an absence of mass effect.5 The present case shared common MRI characteristics of meningioangiomatosis as reported in humans. The T1W hypointense signal, as seen in this case, has been associated with edema, hemosiderin as a consequence of brain hemorrhage, or calcifications. The presence of calcifications and low signal intensity on T2W images are the most specific features of meningioangiomatosis in humans.5 Calcifications were not identified in the present case, similar to other reports of dogs with meningioangiomatosis.1–4 If present, calcifications may be more easily detected on CT scan of the brain.
On MRI, meningeal enhancement associated with adjacent parenchymal T2W hyperintensity, T1W FLAIR hypointensity, and maximal intra-axial enhancement at T5, in the absence of a mass effect, should lead to the inclusion of meningioangiomatosis in the list of differential diagnoses in a young dog with clinical signs consistent with an ipsilateral brainstem and thalamocortex lesion. This is especially true if CSF analysis is not consistent with inflammation. These findings, combined with an absence of response to infectious, anti-inflammatory, and immunosuppressive drugs, should also raise suspicion of meningioangiomatosis in dogs. As observed in the present case, these drugs have not demonstrated clinical benefits in humans with meningioangiomatosis. Treatment of meningioangiomatosis may remain symptomatic (ie, antiseizure medication), especially if lesions are inaccessible for surgical resection. When feasible, surgical resection may be curative, as described in 1 veterinary patient with an excellent reported outcome.2
References
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Roux A, Zanello M, Mancusi RL, et al. Meningioangiomatosis: multimodal analysis and insights from a systematic review. Neurology. 2021;96(6):274–286. doi:10.1212/WNL.0000000000011372
