@article{asakawa_mackillop_olby_robertson_cullen_2010, title={Imaging diagnosis-neuronal ceroid lipofuscinosis with a chronic subdural hematoma}, volume={51}, number={2}, journal={Veterinary Radiology & Ultrasound}, author={Asakawa, M. G. and Mackillop, E. and Olby, N. J. and Robertson, I. D. and Cullen, J. M.}, year={2010}, pages={155–158} }
 @article{leigh_mackillop_robertson_hudson_2008, title={Clinical anatomy of the canine brain using magnetic resonance imaging}, volume={49}, ISSN={["1740-8261"]}, DOI={10.1111/j.1740-8261.2008.00336.x}, abstractNote={The purpose of this study was to produce an magnetic resonsnce (MR) image atlas of clinically relevant brain anatomy and to relate this neuroanatomy to clinical signs. The brain of a large mixed breed dog was imaged in transverse, sagittal, and dorsal planes using a 1.5 T MR unit and the following pulse sequences: Turbo (fast) spin echo (TSE) T2, T1, and T2‐ weighted spatial and chemical shift‐encoded excitation sequence. Relevant neuroanatomic structures were identified using anatomic texts, sectioned cadaver heads, and previously published atlases. Major subdivisions of the brain were mapped and the neurologic signs of lesions in these divisions were described. TSE T2‐weighted images were found to be the most useful for identifying clinically relevant neuroanatomy. Relating clinical signs to morphology as seen on MR will assist veterinarians to better understand clinically relevant neuroanatomy in MR images.}, number={2}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={Leigh, Edmund J. and Mackillop, Edward and Robertson, Ian D. and Hudson, Lola C.}, year={2008}, pages={113–121} }
 @article{mackillop_thrall_ranck_linder_munana_2007, title={Imaging diagnosis-synchronous primary brain tumors in a dog}, volume={48}, ISSN={["1058-8183"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-35448932842&partnerID=MN8TOARS}, DOI={10.1111/j.1740-8261.2007.00294.x}, abstractNote={Four-year-old, neutered male, Bassett Hound. The dog was referred for progressive neurologic dysfunction of approximately 1 month. He would occasionally circle to the right and had developed behavior changes. Two weeks before evaluation the dog began drifting to the left when ambulating and would fall over after shaking his head. Signs of vestibular disequilibrium progressed to falling and rolling to the left. There was mild dehydration (<5%), markedly depressed mentation, and moderate vestibular ataxia with a tendency to stumble to the left. When supported, the dog would circle aimlessly to the right. Menace response was absent in the left eye. Vertical and occasional beats of horizontal nystagmus with a fast-phase to the right were noted in both eyes upon neck extension. Postural reactions were decreased in the left thoracic and pelvic limbs and dysmetric in the right thoracic and pelvic limbs. Neuroanantomic localization was multifocal: right forebrain and caudal fossa. A solitary caudal fossa mass with secondary obstructive hydrocephalus was also considered. Vestibular signs were thought to be consistent with a right-sided paradoxical central vestibular lesion although multifocal cerebellovestibular disease could not be excluded. The differential diagnosis included meningoencephalitis, neoplasia, brain abscess or congenital anomaly. Magnetic resonance (MR) imaging of the brain was performed using a 1.5 T magnet. Two anatomically distant brain masses with disparate features were identified (1, 3). T2-weighted transverse spin echo magnetic resonance image (4000/91) of a cerebellar primitive neuroectodermal tumor. The tumor is mildly T2 hyperintense with a large cystic region in the right dorsolateral aspect. That the hyperintense region is cystic is based on its hypointense appearance in fluid-attenuated inversion recovery images (not shown). T2-weighted transverse spin echo magnetic resonance image (4000/91) of the pilocytic astrocytoma in the right thalamus. Note the ill-defined mass effect, moderate T2-intensity, and peritumoral edema tracking along cerebral white matter (arrow). The first was an approximately 1.5–2.0 cm, mildly T2-hyperintense, ill defined, partially cystic, mass in the right cerebellar hemisphere that was causing mild compression of the brainstem (Fig. 1). In a T2*-weighted gradient echo sequence there were multiple susceptibility artifacts consistent with intralesional hemorrhage (Fig. 2). There was faint, wispy contrast enhancement of this mass. The mass caused overcrowding of the caudal fossa, and faint T2-hyperintensity was present in the cervical spinal cord at the C2 level, consistent with syringohydromyelia. T2*-weighted transverse gradient echo magnetic resonance image (875/26/20°), of the cerebellar primitive neuroectodermal tumor. This image was acquired 5 mm rostral to the image in Fig. 1. There are multiple signal voids (arrow head) representing susceptibility artifact from intratumoral hemorrhage. There was a second similarly sized mass located in the right, ventral aspect of the thalamus at the level of the sella turcica with extension into the right frontal lobe. The imaging characteristics of this mass were different from the cerebellar mass as it had greater T2 intensity, marked adjacent T2 hyperintensity consistent with vasogenic edema, and no evidence of intralesional hemorrahge (Fig. 3). Following contrast medium administration there was faint enhancement of the forebrain mass itself, as well as wispy peripheral enhancement suggestive of peripheral neovascularization. The different imaging characteristics of these masses suggested disparate etiologies. The characteristics of the cerebellar mass suggested it might be associated with a vascular event with resultant necrosis and hemorrhage while the features of the forebrain mass were more consistent with a glial tumor. However, the imaging features were not specific and other etiologies for these lesions included metastatic neoplasia, inflammatory disease or multifocal primary brain tumors. Following MR imaging mannitol was administered intravenously and CSF was collected from the cerebellomedullary cistern. CSF analysis was within the normal reference range. Progressive neurological signs prompted a CT-guided brain biopsy. In CT images, the forebrain mass did not contrast enhance and there was a subtle hypoattenuating focus within the mass, consistent with edema. The cerebellar mass was hyperattenuating relative to adjacent neuropil and contained a central hypoattenuating focus consistent with cystic fluid, necrosis, or chronic hemorrhage. Samples of the forebrain mass were obtained with a core biopsy needle using CT guidance and submitted for stat frozen section histologic assessment. Despite sampling from the apparent epicenter of the mass, the biopsy was interpreted as mild gliosis without evidence of inflammation or neoplasia. The dog failed to adequately ventilate following anesthesia and was euthanized based on the poor prognosis for recovery. The right cerebral hemisphere was swollen with moderate subdural hemorrhage. The caudal aspect of the cerebellum was herniated into the fourth ventricle and compressed the associated segment of brain stem, which had moderate patchy hemorrhage. There was no evidence of transtentorial brain herniation. Following transverse sectioning of the brain, a poorly defined, slightly expansile pale mass, with fine stippling was centered in the right thalamus. There was a more discrete, spheroid mass in the cerebellum that was mottled dark brown-red and effaced approximately 70% of the right hemisphere. Microscopically, the forebrain mass was composed of elongated fascicles of slender spindle cells with a fibrillary cytoplasm and thin oval nuclei (Fig. 4A). This mass had diffuse, strong immunoreactivity for glial fibrillary acidic protein (GFAP) and mild to moderate regional immunoreactivity for vimentin but staining was negative for cytokeratin, neuron-specific enolase (NSE), neurofilament, and synaptophysin. The histological diagnosis was astrocytoma with pilocytic features. Photomicrographs of two primary brain tumors in a dog. (A) Thalamus, astrocytoma with pilocytic features composed of discrete fascicles of long slender spindle cells with hyperchromatic elongated nuclei and pale abundant fibrillary cytoplasm. (B) Cerebellum, primitive neuroectodermal tumor, consistent with medullobastoma, formed by sheets of densely packed round to angular small cells with scant cytoplasm and round nuclei. Hematoxylin and eosin, 200 × . The cerebellar mass was distinctly different from the forebrain mass, being composed of dense sheets of small, round to angular cells, with hyperchromatic round nuclei (Fig. 4B). Scattered tumor cells had increased amounts of eosinophilic cytoplasm. Occasionally small cells arranged in rosette-like aggregates. Pyknotic debris was scattered throughout the mass, and there were multiple foci of hemorrhage. Small patchy areas of neoplastic cells exhibited mild immunoreactivity for vimentin but cells lacked specific staining for cytokeratin, GFAP, NSE, neurofilament, synaptophysin, CD3 or CD79a. Individual cells distributed throughout the mass stained for GFAP and were consistent with reactive astrocytes. Morphology supported a primitive neuroectodermal tumor (PNET) in the cerebellum, consistent with a medulloblastoma. We conclude that our patient developed two independent synchronous brain tumors. Multifocal brain lesions may occur from inflammatory, neoplastic, vascular, metabolic, or degenerative etiologies. Cerebrospinal fluid analysis is often used to distinguish inflammatory disease from tumors, although some tumors may be associated with pleocytosis. A multifocal distribution of intracranial masses is suggestive of metastatic neoplasia; however, multiple primary brain tumors or a combination of primary and secondary brain tumors should be considered when brain masses have disparate MR imaging characteristics, as seen here. Multiple intracranial tumors are found in humans with brain metastasis but may also be found with certain heritable neurocutaneous syndromes (syn. phakomatoses) such as neurofibromatosis types 1 and 2 (NF1 and NF2).1,2 For example, people with NF1 are prone to optic nerve gliomas and/or juvenile pilocytic astrocytomas whereas NF2 is associated with either bilateral vestibulocochlear nerve (acoustic) schwannomas or an acoustic schwannoma and another primary brain tumor.2 In one study in dogs, 39/170 (23%) of dogs with a primary brain tumor had at least one other unrelated tumor.3 Interestingly, six of 170 (3.5%) had a second unrelated intracranial neoplasm. In most of these animals (4/6) the second tumor was a pituitary adenoma, although one dog had a meningioma and an astrocytoma. In contrast, multiple menginiomas may be found in as many as 17% of cats with meningioma.4 We found two reports of multiple histologically distinct brain tumors in dogs; one dog had an oligodendroglioma and a meningioma while the other had an oligodendroglioma and metastatic mammary carcinoma.1,5 Both patients were Boxer dogs, a breed predisposed to glioma.1 Multiple histologically distinct brain tumors are a rare occurrence in people without phakomatosis or exposure to ionizing radiation.6,7 Anatomically distant brain tumors, such as in our dog, may reflect coincidental tumorigenesis; alternatively, a genetic abnormality or exposure to a carcinogen may predispose to multifocal neoplasia. It has been speculated that adjacent or collision tumors may result from neoplastic transformation of peritumoral tissue because of chronic inflammation.6 In many instances of multifocal primary intracranial neoplasia, the second tumor is an incidental finding. Therapy is initially directed at the symptomatic tumor unless both tumors can be removed through the same surgical approach.7 Primary brain tumors usually occur in older dogs.8 There are, however, a number of reports of astrocytomas in young dogs such as this animal and gliomas are one of the most common malignancies in children.9 On MR imaging, canine astrocytomas are usually ill-defined intraparenchymal space-occupying masses that are hyperintense on T2-weighted images and hypointense on T1-weighted images.10 Astrocytomas may be associated with mild to marked peritumoral edema and as in this dog extensive peritumoral edema may obscure tumor boundaries. Astrocytomas have variable enhancement patterns but are often heterogenous.10 In our dog, faint contrast enhancement and extensive peritumoral edema made biopsy of the mass difficult and samples were mostly composed of rarefied neuropil with reactive gliosis. Primitive neuroectodermal tumors are rare and thought to arise from neoplastic transformation of embryonal neuroectoderm. The World Health Organization (WHO) for classification of nervous system tumors in domestic animals defines PNET as a generic term for brain tumors that are histologically indistinguishable from medulloblastoma—which is the common term used for this tumor type in the cerebellum.11 MR imaging and CT characteristics of the cerebellar tumor in this dog support the diagnosis of medulloblastoma. PNETs are primarily found in adult dogs (range 3–10 years old) but there are reports of medulloblastoma in dogs ≤2 years of age.12 In our dog, lack of association with the ventricular system argues against another primitive neoplasm, such as an anaplastic ependymal tumor. Medulloblastoma and pilocytic astrocytoma are the two most common brain tumors in children and the simultaneous occurrence of both tumors in this relatively young dog is extremely unusual.2,13 Medulloblastoma is a malignant embryonal tumor that is thought to be derived from either the external germinal layer of the cerebellum or subependymal matrix cells.14 On MR imaging, human medulloblastomas are predominantly isointense to grey matter on T2-weighted and fluid-attenuated inversion recovery (FLAIR) sequences and hypointense or isointense to grey matter on T1-weighted sequences. Though in our dog the cerebellar tumor was not T2-isointense to brain, its T2-intensity was lower than the forebrain astrocytoma. In people, it is not uncommon for there to be regions of heterogeneity in medulloblastomas because of tumor hemorrhage, necrosis, or cavitation.2,15 Contrast enhancement is usually mild to moderate. One reported canine medulloblastoma had similar MR imaging characteristics to the cerebellar tumor in our dog.12 Complete neuraxial MR imaging has been recommended in the presurgical evaluation of people with suspected medulloblastoma because intrathecal or drop metastasis may be found in approximately 40% of patients.15 Diffusion-weighted imaging (DWI) is used in people to help distinguish PNETs from other brain tumors. DWI has historically been used in the diagnosis of stroke because of its capacity to identify the restricted movement of water protons, a characteristic feature of acute stroke. Of 12 human PNETs, including nine medulloblastomas, tumors were characterized as having restricted water diffusion.15 Medulloblastomas are densely cellular and have a high nuclear:cytoplasmic ratio which may restrict the motion of both extra- and intracellular water protons.15 These same tumor characteristics are thought to be the reason that medulloblastomas are hyperattenuating on CT images and predominantly isointense on T2-weighted and FLAIR sequences.2 In our dog, the combination of a densely cellular neoplasm along with intratumoral hemorrhage may explain the hyperattenuation on CT images. Although uncommon, multiple histologically distinct intracranial tumors should be considered in dogs that have multifocal brain masses with disparate MR imaging characteristics. A heterogeneous, slightly T2 hyperintense cerebellar mass lesion should raise the index of suspicion for a medulloblastoma. The authors would like to thank Drs. Talmage Brown, Brian Summers, Tom Van Winkle, Jim Cooley, and Jon Patterson for their histopathologic review of tissue from this dog.}, number={6}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={MacKillop, Edward and Thrall, Donald E. and Ranck, Rose S. and Linder, Keith E. and Munana, Karen R.}, year={2007}, pages={550–553} }
 @article{mackillop_olby_linder_brown_2007, title={Intramedullary cavernous malformation of the spinal cord in two dogs}, volume={44}, ISSN={["1544-2217"]}, DOI={10.1354/vp.44-4-528}, abstractNote={ Intramedullary cavernous malformations (CVMs) of the spinal cord were diagnosed in 2 adult dogs that presented for paraparesis. An intramedullary spinal cord lesion was identified on a myelogram in the first dog, and expansion of the vertebral canal was evident on radiographs in the second. Extensive intraparenchymal hemorrhage was found on gross postmortem examination in both dogs, and a distinct lobulated intramedullary mass was evident in the second dog. Microscopically, both lesions were composed of dilated, thin-walled vascular channels with little-to-no intervening neural parenchyma. Both dogs had evidence of channel thrombosis along with perilesional hemorrhage and hemosiderin accumulation. The second dog had additional degenerative changes, including thickened fibrous channel walls with hyalinization, foci of mineralization, and occasional tongues of entrapped gliotic neuropil. CVMs appear to be an uncommon cause of both acute and chronic spinal cord disease in the dog. }, number={4}, journal={VETERINARY PATHOLOGY}, author={Mackillop, E. and Olby, N. J. and Linder, K. E. and Brown, T. T.}, year={2007}, month={Jul}, pages={528–532} }
 @article{mackillop_schatzberg_lahunta_2006, title={Intracranial epidermoid cyst and syringohydromyelia in a dog}, volume={47}, ISSN={["1740-8261"]}, DOI={10.1111/j.1740-8261.2006.00150.x}, abstractNote={A 5‐year‐old female Cocker Spaniel dog had a sudden onset of vestibular disease that localized to the caudal fossa. Upon computed tomography of the brain, a large, hypoattenuating mass with a slight peripheral ring enhancement pattern was detected ventral to the cerebellum. A hypoattenuating region was also identified in the center of the C2 spinal cord segment, consistent with syringohydromyelia. Postmortem examination of the brain revealed a fluid filled, cystic mass located dorsal to medulla oblongata that caused severe compression of the overlying cerebellum. The histopathologic diagnosis was an epidermoid cyst. Extensive syringohydromyelia and obstructive hydrocephalus were identified, both thought to be secondary to overcrowding of the caudal fossa.}, number={4}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={MacKillop, Edward and Schatzberg, Scott J. and Lahunta, Alexander}, year={2006}, pages={339–344} }