Cortical motor threshold determination in dogs.

In humans, determining the cortical motor threshold (CMT) is a critical step in successfully applying a transcranial magnetic stimulation (TMS) treatment. Stimulus intensity, safety and efficacy of a TMS treatment are dependent of the correct assessment of the CMT. Given that TMS in dogs could serve as a natural animal model, an accurate and reliable technique for the measurement of the CMT should be available for dogs. Using a visual descending staircase paradigm (Rossini paradigm), the CMT repeatability was assessed and compared to the electromyographic (EMG) variant. The influence of a HF-rTMS treatment on the CMT was examined. Subsequently, the CMT was measured under sedation and general anaesthesia. Finally, the coil-cortex distance was associated with the CMT, weight, age and gender. During one year the CMT was measured three times, during which it remained constant, although a higher CMT was measured (40% higher machine output) when using EMG (P-value < .001) and under general anaesthesia (P-value = .005). On average, a 40% and 12% higher machine output were registered. An aHF-rTMS protocol does not influence the CMT. Males have on average a 5.2 mm larger coil cortex distance and an 11.81% higher CMT. The CMT was positively linearly associated (P-value < .05) with the weight and age of the animals. Only within female subjects, a positive linear association was found between the CMT and the coil-cortex distance (P-value = .02). Using the visual Rossini paradigm, the CMT can be reliably used over time and during a TMS treatment. It has to be kept in mind that when using EMG or assessing the CMT under general anaesthesia, a higher CMT is to be expected. As in humans, every parameter that influences the coil-cortex distance may also influence the CMT.

Changes in canine cerebral perfusion after accelerated high frequency repetitive transcranial magnetic stimulation (HF-rTMS): A proof of concept study.

Repetitive transcranial magnetic stimulation (rTMS) has been proposed as a treatment for several neuropsychiatric disorders in human beings, but the neurobiological effects of rTMS in dogs have not been investigated to date. A proof of concept study was designed to evaluate the effect of rTMS on cerebral perfusion, measured with single photon emission computed tomography (SPECT), in dogs. An accelerated high frequency (aHF)-rTMS (20Hz) protocol was applied to the canine left frontal cortex. To accurately target this area, eight dogs underwent a 3 Tesla magnetic resonance imaging (MRI) scan before stimulation. The left frontal cortex was subjected to five consecutive aHF-rTMS sessions with a figure-of-eight coil designed for human beings at an intensity of 110% of the motor threshold. The dogs underwent 99mTc-d,1 hexamethylpropylene amine oxime (HMPAO) SPECT scans 1 week prior to and 1day after the stimulations. Perfusion indices (PIs) were determined semi-quantitatively; aHF-rTMS resulted in significantly increased PIs in the left frontal cortex and the subcortical region, whereas no significant differences were noted for the other regions. Behaviour was not influenced by the stimulation sessions. As has been observed in human beings, aHF-rTMS applied to the left frontal cortex alters regional cerebral perfusion in dogs.

Biodistribution and tolerance of intravenous iodine-131-labelled hypericin in healthy dogs.

Hypericin (Hyp) is a necrosis-avid compound that can be efficiently labelled with radioiodine for both diagnostic and therapeutic purposes. Before 131 I-Hyp can be considered as a clinically useful drug in a combination therapy for canine cancer patients, evaluation of its toxicity is necessary. The aim of this study was to investigate the biodistribution and tolerance of a single dose administration of 131 I-Hyp. Three healthy dogs were included. 131 I-Hyp at a dose of 0.2 mg/kg and an activity of 185 MBq was intravenously injected. The effects on physical, haematological and biochemical parameters were characterized and the biodistribution and elimination pattern, the effective half-life and dose rate were assessed. Drug-related adverse events were limited to mild gastrointestinal signs, resolving within 48 hours. No significant differences were found in blood haematology and serum biochemistry before and after treatment. Following administration, highest percentage of injected dose (%ID ± SD) was found in the liver (5.5 ± 0.33), the lungs (4.17 ± 0.14) and the heart (3.11 ± 0.78). After 24 hours, highest %ID was found in colon (4.25 ± 1.45) and liver (3.45 ± 0.60). Clearance from all organs was effective within 7 days. Effective half-life was established at 80 hours, and the dose rate fell below <20 µSv/h at 1 m within 1 day. The current study reveals that single dose treatment with 131 I-Hyp at the described dose is well tolerated by healthy dogs and supports the use of radioiodinated hypericin in a combination therapy for canine cancer patients.