Ronaldo C. da Costa

Intrathecal administration of recombinant human N-acetylgalactosamine 4-sulfatase to a MPS VI patient with pachymeningitis cervicalis.

In mucopolysaccharidosis VI, or Maroteaux-Lamy syndrome, deficiency of N-acetylgalactosamine 4-sulfatase leads to storage of glycosaminoglycans (GAGs) and MPS VI patients often develop spinal cord compression during the course of the disease due to GAG storage within the cervical meninges, requiring neurosurgical intervention, as intravenous (IV) enzyme replacement therapy (ERT) is not expected to cross the blood-brain barrier. We report the use of intrathecal (IT) recombinant human N-acetylgalactosamine 4-sulfatase (arylsulfatase B, or ASB) in a MPS VI child with spinal cord compression whose parents initially refused the surgical treatment. Assessments were performed at baseline, with clinical, neurological and biochemical evaluations, urodynamic studies and MRI of the CNS. Changes on these parameters were evaluated after IT infusions of ASB administered monthly via lumbar puncture (LP) in a IV ERT naive patient. To our knowledge, this was the first MPS VI patient who received IT ERT. Despite significant urodynamic improvement and some neurological amelioration, the patient developed worsening of walking capacity. After IV ERT was started, the patient presented with a generalized hypotonia and a life-saving surgical fixation of the neck was then performed. The results observed on this MPS VI patient suggest that instability of the cervical vertebrae could be unmasked by IV ERT as joint storage is reduced, and the decrease in neck stiffness and stability could confound the expected improvement of SCC manifestations following IT ERT. The study of further patients, if possible in a clinical trial setting, is needed to evaluate the potential of a non-surgical IT ERT treatment of SCC for MPS VI.

Advanced Imaging of the Spine in Small Animals

Computed tomography (CT) and magnetic resonance imaging (MRI) are extremely valuable techniques in the diagnosis of spinal disorders. This article reviews the fundamentals, indications, key technical aspects, and advantages and disadvantages of each modality. The CT and MRI features of common spinal diseases are discussed and illustrated. Comparative studies using advanced and nonadvanced imaging modalities are also presented.

Outcome of medical and surgical treatment in dogs with cervical spondylomyelopathy : 104 cases (1988-2004)

OBJECTIVE To compare outcomes and survival times for dogs with cervical spondylomyelopathy (CSM; wobbler syndrome) treated medically or surgically. DESIGN Retrospective case series. ANIMALS 104 dogs. PROCEDURES Medical records of dogs were included if the diagnosis of CSM had been made on the basis of results of diagnostic imaging and follow-up information (minimum, 6 months) was available. Ordinal logistic regression was used to compare outcomes and the product-limit method was used to compare survival times between dogs treated surgically and dogs treated medically. RESULTS 37 dogs were treated surgically, and 67 were treated medically. Owners reported that 30 (81%) dogs treated surgically were improved, 1 (3%) was unchanged, and 6 (16%) were worse and that 36 (54%) dogs treated medically were improved, 18 (27%) were unchanged, and 13 (19%) were worse. Outcome was not significantly different between groups. Information on survival time was available for 33 dogs treated surgically and 43 dogs treated medically. Forty of the 76 (53%) dogs were euthanized because of CSM. Median and mean survival times were 36 and 48 months, respectively, for dogs treated medically and 36 and 46.5 months, respectively, for dogs treated surgically. Survival times did not differ significantly between groups. CONCLUSIONS AND CLINICAL RELEVANCE In the present study, neither outcome nor survival time was significantly different between dogs with CSM treated medically and dogs treated surgically, suggesting that medical treatment is a viable and valuable option for management of dogs with CSM.

COMPUTED TOMOGRAPHY MYELOGRAPHIC FINDINGS IN DOGS WITH CERVICAL SPONDYLOMYELOPATHY

Computed tomography (CT) myelography is used occasionally in the diagnosis of cervical spondylomyelopathy, but the type of lesion found in large- versus giant-breed dogs using this modality has not been characterized. Our purpose was to report the frequency of compressive lesions in large- and giant-breed dogs with cervical spondylomyelopathy and imaged using CT myelography. Fifty-eight dogs were retrospectively studied, 23 large-breed and 35 giant-breed dogs. Multiple sites of compression were found in 12 large-breed dogs (52.2%) compared to 30 (85.8%) giant-breed dogs. The main site of compression was at C5-6 and C6-7 in both large-breed (91.3%) and giant-breed (72.4%) dogs. The main cause and direction of compression was disc-associated and ventral in 19 (82.6%) of the large-breed dogs while osseous changes were the primary cause of compression in 27 (77.2%) of the giant-breed dogs, with most compressions being lateral (51.4%), followed by dorsolateral (14.2%). Osseous compression was observed at C7-T1 in eight giant-breed dogs (22.8%), and at T1-T2 or T2 only in five dogs (14.3%). Four of 23 large-breed dogs (17.4%), and seven (20%) of 35 giant-breed dogs had spinal cord atrophy. Therefore, giant-breed dogs often have multiple compressions, usually caused by osseous changes causing lateralized compressions. In large-breed dogs most compressions are disc-associated and located ventrally. Considering the number of giant-breed dogs with compressions at C7-T1, T1-2, and T2, it is important to include the cranial thoracic region when imaging dogs suspected of having cervical spondylomyelopathy.

A CLN8 nonsense mutation in the whole genome sequence of a mixed breed dog with neuronal ceroid lipofuscinosis and Australian Shepherd ancestry

The neuronal ceroid lipofuscinoses (NCLs) are hereditary neurodegenerative diseases characterized by seizures and progressive cognitive decline, motor impairment, and vision loss accompanied by accumulation of autofluorescent lysosomal storage bodies in the central nervous system and elsewhere in the body. Mutations in at least 14 genes underlie the various forms of NCL. One of these genes, CLN8, encodes an intrinsic membrane protein of unknown function that appears to be localized primarily to the endoplasmic reticulum. Most CLN8 mutations in people result in a form of NCL with a late infantile onset and relatively rapid progression. A mixed breed dog with Australian Shepherd and Blue Heeler ancestry developed neurological signs characteristic of NCL starting at about 8months of age. The signs became progressively worse and the dog was euthanized at 21months of age due to seizures of increasing frequency and severity. Postmortem examination of the brain and retinas identified massive accumulations of intracellular autofluorescent inclusions characteristic of the NCLs. Whole genome sequencing of DNA from this dog identified a CLN8:c.585G>A transition that predicts a CLN8:p.Trp195* nonsense mutation. This mutation appears to be rare in both ancestral breeds. All of our 133 archived DNA samples from Blue Heelers, and 1481 of our 1488 archived Australian Shepherd DNA samples tested homozygous for the reference CLN8:c.585G allele. Four of the Australian Shepherd samples tested heterozygous and 3 tested homozygous for the mutant CLN8:c.585A allele. All 3 dogs homozygous for the A allele exhibited clinical signs of NCL and in 2 of them NCL was confirmed by postmortem evaluation of brain tissue. The occurrence of confirmed NCL in 3 of 4 CLN8:c.585A homozygous dogs, plus the occurrence of clinical signs consistent with NCL in the fourth homozygote strongly suggests that this rare truncating mutation causes NCL. Identification of this NCL-causing mutation provides the opportunity for identifying dogs that can be used to establish a canine model for the CLN8 disease (also known as late infantile variant or late infantile CLN8 disease).

Kinematic Motion Patterns of the Cranial and Caudal Canine Cervical Spine

OBJECTIVE To define the kinematic motion patterns of the canine cervical spine, with a particular emphasis on identifying differences between the cranial (C(2)-C(4)) and caudal (C(5)-C(7)) segments, and to determine the significance of coupled motions (CM) in the canine cervical spine. STUDY DESIGN Cadaveric biomechanical study. SAMPLE POPULATION Cervical spines of 8 Foxhounds. METHODS Spinal specimens were considered free of pathology based on radiographic, computed tomography, and magnetic resonance imaging examinations. All musculature was removed without damaging ligaments or joint capsules. Spines were mounted in a customized pure-moment spine testing jig, and data were collected using an optoelectronic motion capture system. Range of motion, neutral zone and CM in flexion/extension, left/right lateral bending and left/right axial rotation were established. Data were analyzed using mixed-effects maximum likelihood regression models. RESULTS Total flexion/extension did not change across the 4 levels. There was no difference between flexion and extension, and no CM was identified. Lateral bending was not different across levels, but tended to be greater in the cranial spine. Axial rotation was ∼2.6 times greater in the caudal segments. Lateral bending and axial rotation were coupled. CONCLUSIONS Kinematics of the cranial and caudal cervical spine differed markedly with greater mobility in the caudal cervical spine.

Incidence of and risk factors for seizures after myelography performed with iohexol in dogs: 503 cases (2002-2004)

OBJECTIVE To establish the incidence of and risk factors for seizures following myelography performed with iohexol in dogs. DESIGN Retrospective case series. ANIMALS 503 dogs. PROCEDURES Medical records were searched for dogs that underwent myelography between April 2002 and December 2004. Data extracted included body weight, breed, age, sex, volume and dose of iohexol, site of injections, location of lesion, duration of anesthesia, surgical procedures immediately after myelography, use of acepromazine, and presence or absence of seizures. RESULTS 15 (3%) dogs had postmyelographic seizures. Risk factors significantly associated with seizures were size of dogs (large dogs were 35.35 times as likely to have seizures as were small dogs), location of contrast medium injection (dogs in which iohexol was injected into the cerebellomedullary cistern were 7.4 times as likely to have seizures as were dogs in which iohexol was injected into the lumbar cistern), location of lesion (dogs with lesions at the level of the cervical portion of the vertebral column were 4.65 times as likely to develop seizures as were dogs with lesions in other regions), and total volume of iohexol. Mean ± SD total volume of iohexol was 11.73 ± 5.52 mL (median, 10.5 mL [range, 3.0 to 21.0 mL]) for dogs that had seizures and 4.57 ± 4.13 mL (median, 3.5 mL [range, 0.75 to 45.0 mL]) for those that did not. CONCLUSIONS AND CLINICAL RELEVANCE Large-breed dogs with cervical lesions and large volumes of iohexol injected into the cerebellomedullary cistern had the highest risk of seizures. The use of contrast medium volumes > 8 mL in large dogs should be avoided, with preference given to injections into the lumbar cistern.

Time-of-flight magnetic resonance angiography of the canine brain at 3.0 Tesla and 7.0 Tesla.

OBJECTIVE To evaluate the ability of 2-D time-of-flight (ToF) magnetic resonance angiography (MRA) to depict intracranial vasculature and compare results obtained with 3.0- and 7.0-T scanners in dogs. ANIMALS 5 healthy Beagles. PROCEDURES 2-D ToF-MRA of the intracranial vasculature was obtained for each dog by use of a 3.0-T and a 7.0-T scanner. Quantitative assessment of the images was obtained by documentation of the visibility of major arteries comprising the cerebral arterial circle and their branches and recording the number of vessels visualized in the dorsal third of the brain. Qualitative assessment was established by evaluation of overall image quality and image artifacts. RESULTS Use of 3.0- and 7.0-T scanners allowed visualization of the larger vessels of the cerebral arterial circle. Use of a 7.0-T scanner was superior to use of a 3.0-T scanner in depiction of the first- and second-order arterial branches. Maximum-intensity projection images had a larger number of vessels when obtained by use of a 7.0-T scanner than with a 3.0-T scanner. Overall, image quality and artifacts were similar with both scanners. CONCLUSIONS AND CLINICAL RELEVANCE Visualization of the major intracranial arteries was comparable with 3.0- and 7.0-T scanners; the 7.0-T scanner was superior for visualizing smaller vessels. Results indicated that ToF-MRA is an easily performed imaging technique that can be included as part of a standard magnetic resonance imaging examination and should be included in the imaging protocol of dogs suspected of having cerebrovascular disease.

Differential diagnosis of spinal diseases.

Preparation of a logical list of differential diagnoses is a key step in the diagnostic approach for dogs and cats with spinal disorders. This article presents the main differential diagnoses for patients with spinal diseases grouped according to lesion localization. The differential diagnoses are divided primarily according to the 4 classic spinal cord divisions, but other important spinal subdivisions are also discussed.

Clinical and MRI Findings in Three Dogs with Polycystic Meningiomas

One spayed female Labrador retriever and two castrated male golden retrievers were evaluated for chronic (i.e., ranging from 3 wk to 24 wk) neurologic signs localizable to the prosencephalon. Signs included seizures, circling, and behavior changes. MRI demonstrated extra-axial, contrast-enhancing, multiloculated, fluid-filled, cyst-like lesions with a mass effect, causing compression and displacement of brain parenchyma. Differential diagnoses included cystic neoplasm, abscess or other infectious cyst (e.g., alveolar hydatid cyst), or fluid-filled anomaly (e.g., arachnoid cyst). The cyst-like lesions were attached to the rostral falx cerebri in all cases. In addition, case 2 had a second polycystic mass at the caudal diencephalon. Surgical biopsy (case 3 with a single, rostral tumor via transfrontal craniectomy) and postmortem histology (in cases 1 and 2) confirmed polycystic meningiomas. Tumor types were transitional (cases 1 and 3) and fibrous (case 2), with positive immunohistochemical staining for vimentin. Case 3 was also positive for E-cadherin, s100, and CD34. In all cases, staining was predominantly negative for glial fibrillary acid protein and pancytokeratins, supporting a diagnosis of meningioma. This report describes the first cases of polycystic meningiomas in dogs. Polycystic meningiomas are a rare, but important, addition to the differential diagnoses for intracranial cyst-like lesions, significantly affecting planning for surgical resection and other therapeutic interventions.