The effect of oral zonisamide treatment on serum phenobarbital concentrations in epileptic dogs.

Zonisamide is used in dogs for the treatment of epileptic seizures. It is predominantly metabolised by CYP450 hepatic enzymes. When used concurrently with phenobarbital (PB), zonisamide clearance is increased and its elimination half-life decreases. However, the effect that zonisamide may have on serum PB concentrations in dogs has not been previously described. Eight dogs diagnosed with idiopathic epilepsy and two dogs with structural epilepsy commenced zonisamide at 8.0 mg/kg/12 h [7.4-10 mg/kg/12 h] following an increase in the frequency of epileptic seizures. Nine dogs were receiving PB every 12 h (4.2 mg/kg/12 h [3.8-6 mg/kg/12 h]), and one dog was receiving PB every 8 h (6 mg/kg/8 h). Following the addition of zonisamide and despite no increase in PB dosage, an increase in phenobarbital serum PB concentration was observed in 9 out of 10 dogs in subsequent measurements. In five dogs, phenobarbital serum concentrations were raised to concentrations higher than the reported hepatotoxic concentrations (trough>35 mg/L). This required a reduction in daily doses of PB. This case series suggests that zonisamide affects the metabolism of PB and causes an increase in PB serum concentrations over time.

Clinical, magnetic resonance imaging, surgical features and comparison of surgically treated intervertebral disc extrusion in French bulldogs.

Intervertebral disc (IVD) extrusion (IVDE) is the most reported neurological condition in French bulldogs (FBD). The aim of this study was to retrospectively evaluate neurological grade, magnetic resonance imaging (MRI), surgical findings and short-term recovery in surgically treated FBD diagnosed with IVDE referred to a single institution between January 2020 and March 2022 and to compare cervical and thoracolumbar IVDE. Data was gathered from medical records and analysed via Fischer's Exact-Test and Kruskal Wallis-tests. Statistical significance was assumed when p < 0.05. Thirty-nine FBD were diagnosed with IVDE. Cervical IVDE (C-IVDE) was diagnosed in 11/39 cases; the C3-C4 IVD space was the most commonly affected site (5/11). Thoracolumbar IVDE (TL-IVDE) was diagnosed in 28 cases; the L3-L4 IVD space was the most commonly affected site (7/28). At admission, C-IVDE was significantly associated with less severe neurological grade (grade 1-2) compared to TL-IVDE (grade 2-5) (p < 0.001). The extruded IVD material (EIVDM) was hypointense in T2w images in 11/11C-IVDE vs. 2/28TL-IVDE, and hypointense in T1w images in 10/11C-IVDE vs. 1/28TL-IVDE. The EIVDM was hyperintense in T2w images in 0/11C-IVDE vs. 26/28TL-IVDE and iso-to-hypointense in T1w images in 1/11C-IVDE vs. 27/28TL-IVDE (p < 0,001). The EIVDM extended over ≥2 IVD spaces in 0/11C-IVDE vs. 19/28TL-IVDE (p < 0,001). 10/11C-IVDE underwent single ventral slot, 1/11C-IVDE underwent unilateral cervical hemilaminectomy. All TL-IVDE underwent unilateral hemilaminectomy and 19/28TL-IVDE underwent unilateral hemilaminectomy over ≥2 IVD spaces (p < 0,001). Haemorrhagic EIVDM was noticed intraoperatively in 1/11C-IVDE vs. 28/28TL-IVDE (p < 0,001). Spinal cord compression was mild in 2/11C-IVDE and 3/28TL-IVDE; moderate in 9/11C-IVDE and 16/28TL-IVDE; severe in 0/11C-IVDE and 8/28TL-IVDE. There was no spinal cord compression in 1/28TL-IVDE with foraminal IVDE. There was no statistical difference between spinal cord compression and IVDE location (p = 0.112). The mean time to improvement was 1.1 day in C-IVDE (range 1-2 days). 90.1% of C-IVDE improved within the first 24 h. The mean time to improvement was 2.1 days in TL-IVDE (range from 1 day to 4 days). All dogs that did not improve (5/39) were grade 5 TL-IVDEs at presentation. In FBD, TL-IVDE tended to cause higher grade of neurological dysfunction, tended to result in compression of neural structures over multiple IVD spaces and required more extensive surgical treatment than C-IVDE.

Case Report: A Novel Lateral Approach to the C7, C8, and T1 Intervertebral Foramina for Resection of Malignant Peripheral Nerve Sheath Neoplasia, Followed by Adjunctive Radiotherapy, in Three Dogs.

This case report describes the diagnosis, management and outcome of three dogs with peripheral nerve sheath tumors (PNSTs) involving the brachial plexus, C7 (case 1), C8 (case 2), and C8 and T1 (case 3) spinal nerves and nerve roots with intrathoracic invasion. Surgical resection required thoracic limb amputation and removal of the first rib, facilitating a novel lateral approach to the spinal nerves and foramina in all cases. This was followed by hemilaminectomy and rhizotomy in cases 1 and 2. Adjunctive radiotherapy was then performed in all dogs. All three dogs regained a good quality of life in the short-term following surgery. Two were euthanased after 3 and 10 months, following detection of a pulmonary mass in one case and multiple thoracic and abdominal masses in the other. The third dog was alive and well at the time of writing (7 months post-surgery). This surgical approach facilitated good access and allowed gross neoplastic tissue to be resected. The ease of surgical access was dependent, to a degree, on the size of the patient. This surgical approach can be considered in cases of PNSTs involving the caudal cervical or cranial thoracic spinal nerves and nerve roots. Adjunctive radiotherapy should be considered as part of a multi-modal approach to these challenging tumors due to the difficulty of achieving clean margins, particularly proximally, even with optimal surgical access.

Case Report: Ventriculoperitoneal Shunting and Radiation Therapy Treatment in a Cat With a Suspected Choroid Plexus Tumor and Hypertensive Hydrocephalus.

A 14-year-old male neutered domestic short-hair cat was presented for a history of behavioral changes and episodes of urinary retention. Neurological examination was consistent with a multifocal intracranial neuroanatomical localization, with suspected right sided lateralisation and suspected raised intracranial pressure (ICP). Brain magnetic resonance imaging (MRI) revealed an intraventricular multilobulated well-defined T2W-hyperintense and T1W-isointense, markedly contrast enhancing mass lesion within the dorsal aspect of the III ventricle extending into the left lateral ventricle, causing hypertensive obstructive hydrocephalus. A ventriculoperitoneal shunt (VPS) was placed within the left lateral ventricle, followed by a radiation therapy (RT) course of 45 Gy total dose in 18 daily fractions. Six-months post-RT, computed tomography revealed mild reduction in mass size and resolution of the hydrocephalus. The patient was neurologically normal with no medical treatment. Raised ICP causes severe clinical signs, can lead to brain ischaemia and herniation, and significantly increases anesthetic risk during RT. Placement of a VPS in cats with hypertensive obstructive hydrocephalus may allow improvement of neurological signs due to raised ICP, and therefore making the patient a more stable candidate for anesthesia and radiation therapy.

Dogs and cats with presumed or confirmed intracranial abscessation have low apparent diffusion coefficient values.

Intracranial abscessation is a life-threatening condition in dogs and cats, and rapid diagnosis is important for prognosis and treatment planning. The aims of this retrospective, single-center, case series study were to describe clinical and MRI diffusion-weighted imaging characteristics in three dogs and three cats with presumed or confirmed intracranial abscessation. All lesions appeared hyperintense on b1000 trace diffusion-weighted images, hypointense on apparent diffusion coefficient (ADC) map, with mean ADC values ranging from 0.37 to 1.24 × 10-3  mm2 /s. The majority (5/6) of the obtained mean ADC values were low (<1.10 × 10-3  mm2 /s), as previously reported in the human literature.

Effects of an immunosuppressive treatment in the GRMD dog model of Duchenne muscular dystrophy.

The GRMD (Golden retriever muscular dystrophy) dog has been widely used in pre-clinical trials targeting DMD (Duchenne muscular dystrophy), using in many cases a concurrent immune-suppressive treatment. The aim of this study is to assess if such a treatment could have an effect on the disease course of these animals. Seven GRMD dogs were treated with an association of cyclosporine A (immunosuppressive dosage) and prednisolone (2 mg/kg/d) during 7 months, from 2 to 9 months of age. A multi-parametric evaluation was performed during this period which allowed us to demonstrate that this treatment had several significant effects on the disease progression. The gait quality as assessed by 3D-accelerometry was dramatically improved. This was consistent with the evolution of other parameters towards a significant improvement, such as the clinical motor score, the post-tetanic relaxation and the serum CK levels. In contrast the isometric force measurement as well as the histological evaluation argued in favor of a more severe disease progression. In view of the disease modifying effects which have been observed in this study it should be concluded that immunosuppressive treatments should be used with caution when carrying out pre-clinical studies in this canine model of DMD. They also highlight the importance of using a large range of multi-parametric evaluation tools to reliably draw any conclusion from trials involving dystrophin-deficient dogs, which reproduce the complexity of the human disease.

Electrophysiological features in dogs with peripheral nerve sheath tumors: 51 cases (1993-2010).

OBJECTIVE: To determine the electrophysiological changes in dogs with peripheral nerve sheath tumors (PNSTs), evaluate the prevalence of these changes, assess the correlation between spontaneous activity in epaxial muscles and proximal invasion by the tumor, and evaluate whether knowledge of electrophysiological changes could be helpful in the imaging diagnosis via CT or MRI. DESIGN: Retrospective case series. ANIMALS: 51 dogs with a histologic (n = 18) or a suspected (33) diagnosis of PNST. PROCEDURES: Clinical, postmortem, and histologic reports and details of electrodiagnostic procedures and CT or MRI reports were studied. Twenty-four CT and 6 MRI reports for dogs with PNSTs were reviewed by a single observer blinded to the diagnosis. RESULTS: Only 2 of the 51 dogs had no electrophysiological changes. The most commonly affected muscles were those innervated by the radial, ulnar, median, tibial-sciatic, and peroneal nerves. Abnormal spontaneous epaxial muscle activity was significantly more frequent in the group with foraminal or spinal invasion by the tumors. Knowledge of the electrophysiological changes increased diagnostic accuracy of CT. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that electrophysiological studies may be sensitive for the detection of PNST and helpful in the imaging diagnosis. Epaxial electromyographic abnormalities appeared to be predictive for intervertebral or vertebral canal invasion by PNSTs in dogs.

Longitudinal ambulatory measurements of gait abnormality in dystrophin-deficient dogs.

BACKGROUND: This study aimed to measure the gait abnormalities in GRMD (Golden retriever muscular dystrophy) dogs during growth and disease progression using an ambulatory gait analyzer (3D-accelerometers) as a possible tool to assess the effects of a therapeutic intervention. METHODS: Six healthy and twelve GRMD dogs were evaluated twice monthly, from the age of two to nine months. The evolution of each gait variable previously shown to be modified in control and dystrophin-deficient adults was assessed using two-ways variance analysis (age, clinical status) with repeated measurements. A principal component analysis (PCA) was applied to perfect multivariate data interpretation. RESULTS: Speed, stride length, total power and force significantly already decreased (p<0.01) at the age of 2 months. The other gait variables (stride frequency, relative power distributions along the three axes) became modified at later stages. Using the PCA analysis, a global gait index taking into account the main gait variables was calculated, and was also consistent to detect the early changes in the GRMD gait patterns, as well as the progressive degradation of gait quality. CONCLUSION: The gait variables measured by the accelerometers were sensitive to early detect and follow the gait disorders and mirrored the heterogeneity of clinical presentations, giving sense to monitor gait in GRMD dogs during progression of the disease and pre-clinical therapeutic trials.

Surgical treatment and radiation therapy of frontal lobe meningiomas in 7 dogs.

The cases of 7 adult dogs with generalized seizures managed by surgical excision and radiation therapy for frontal lobe meningiomas were reviewed. The neurological examination was unremarkable in 6 of the 7 dogs. Five dogs were operated on using a bilateral transfrontal sinus approach and 2 using a unilateral sinotemporal approach to the frontal lobe. One dog was euthanized 14 d after surgery; radiation therapy was initiated 3 wk after surgery in the remaining 6 dogs. Long-term follow-up consisted of neurological examination and magnetic resonance imaging (MRI) and/or computed tomography (CT) scan after radiation therapy. The mean survival time for dogs that had surgery and radiation therapy was 18 mo after surgery. Frontal lobe meningiomas have been associated with poor prognosis. However, the surgical approaches used in these cases, combined with radiation therapy, allow a survival rate for frontal lobe meningiomas similar to that for meningiomas located over the cerebral convexities.

Botulism in 2 urban dogs.

Two dogs from the same owner were referred for ascending weakness and paresis of 2 to 3 days duration. Electromyography and electroneurography determined that there were normal F-waves, decreased compound action potential, and decreased activity on repetitive nerve stimulation. These findings were valuable in diagnosing botulism in the dogs.

Gait analysis using accelerometry in dystrophin-deficient dogs.

Dogs affected with Golden Retriever Muscular Dystrophy (GRMD) exhibit striking clinical similarities with patients suffering from Duchenne muscular dystrophy (DMD), particularly gait impairments. The purpose of this study was to describe the use and reliability of accelerometry in gait assessment of dogs with muscular dystrophy. Eight healthy and 11 GRMD adult dogs underwent three gait assessment sessions, using accelerometry. Three-axial recordings of accelerations were performed, and gait variables calculated. Total power, force and regularity of accelerations, stride length and speed, normalized by height at withers, stride frequency, and cranio-caudal power were significantly decreased, whereas medio-lateral power was significantly increased in GRMD dogs. Moreover, these variables were repeatable within and between sessions. Accelerometry provides reliable variables which highlight specific gait patterns of GRMD dogs, describing objectively and quantitatively their slow, short-stepped, and swaying gait. As it is easy to set-up, quick to perform and inexpensive, accelerometry represents a useful tool, to assess locomotion during pre-clinical trials.