Clinical efficacy and tolerability of zonisamide monotherapy in dogs with newly diagnosed idiopathic epilepsy: Prospective open-label uncontrolled multicenter trial.

BACKGROUND: Zonisamide (ZNS) is a newer generation antiseizure medication (ASM) used to treat epilepsy in dogs and cats. However, scientific and clinical information, particularly regarding monotherapy, is limited. OBJECTIVES: To evaluate the antiseizure efficacy and tolerability of ZNS monotherapy in dogs with newly diagnosed idiopathic epilepsy (IE). ANIMALS: Study included 56 client-owned dogs newly diagnosed with IE. METHODS: This was a prospective multicenter, open-label, uncontrolled study. All dogs were ASM-naïve and had ≥2 seizures within 12 weeks. Dogs were administered 2.7-14.4 mg/kg ZNS PO q12h and followed up for ≥12 weeks. Data from the 12-week maintenance treatment period were compared with those from the 4- to 12-week pretreatment period for efficacy evaluation. Data from the entire ZNS administration period were used to assess tolerability. RESULTS: Fifty-six dogs were included in our study. Of the dogs, 53 were assessed for efficacy; 40 (76%) had a ≥ 50% reduction in seizure frequency, and 29 (55%) achieved seizure freedom. For 90% of the dogs with ≥50% reduction in seizure frequency, the mean ZNS dose was 4.8 (range, 2.7-8.6) mg/kg q12h and the mean trough plasma ZNS concentration was 18.9 (range, 8.0-48.0) µg/mL. In 7 of the 56 dogs (13%), reduced activity, decreased appetite, vomiting, hindlimb weakness, soft stools, or constipation was observed, albeit mild and temporary. Laboratory tests revealed no relevant changes. CONCLUSIONS AND CLINICAL IMPORTANCE: Our study suggests that ZNS monotherapy is effective and well-tolerated in dogs with newly diagnosed IE.

Somatosensory evoked potentials of the tibial nerve during the surgical decompression of thoracolumbar intervertebral disk herniation in dogs.

This study aimed to identify the impact on spinal cord integrity and determine the electrophysiological safety level during surgery for thoracolumbar intervertebral disk herniation in dogs. A total of 52 dogs diagnosed with thoracolumbar intervertebral disk herniation were enrolled. The tibial nerve somatosensory evoked potential elicited on the scalp by stimulation of the tibial nerve was recorded before and during hemilaminectomy. Both the amplitude and latency of the somatosensory evoked potential were periodically registered, and the percentage changes from the pre-operative control values (amplitude rate and latency rate) were calculated. When the multifidus muscles were retracted after removal from the spinous processes and vertebrae, the somatosensory evoked potential amplitude rate decreased in all dogs, while the latency rate increased in 33 dogs examined. The amplitude rate remained unchanged during the halting procedure, loosening retraction, and hemilaminectomy. After removing the disc material from the spinal canal, the amplitude rate was increased. The somatosensory evoked potential latency increased when the multifidus muscles were retracted and shortened after multifidus muscles closure in four cases. The outcome of all cases showed improvement in clinical signs 7 days after operation. Spinal cord conduction is impaired by retraction of the multifidus muscles and improved by removal of disk materials. Maintaining intraoperative SEP amplitudes above 50% of control may help avoid additional spinal cord injury during surgery. Since we have no case that worsened after the surgery, however, further studies are necessary to confirm this proposal.

F-wave parameters for the tibial nerve in Miniature Dachshunds with and without naturally acquired thoracolumbar intervertebral disk herniation.

OBJECTIVE: To determine values of F-wave parameters for the tibial nerve in clinically normal Miniature Dachshunds and those with thoracolumbar intervertebral disk herniation (IVDH). ANIMALS: 53 Miniature Dachshunds (10 clinically normal and 43 with various clinical grades of thoracolumbar IVDH). PROCEDURES: F-waves were elicited in the interosseous muscles of 1 hind limb in each dog by stimulation of the tibial nerve. F-wave parameters were measured for 32 stimuli/dog, and mean values were calculated. Linear regression was performed to assess correlations between F-wave parameters and clinical severity of IVDH. RESULTS: For clinically normal dogs, mean ± SD values of shortest F-wave latency, mean F-wave conduction velocity, mean F-wave duration, and ratio of the mean F-wave amplitude to M response amplitude were 8.6 ± 0.6 milliseconds, 83.7 ± 6.1 m/s, 6.6 ± 1.5 milliseconds, and 9.8 ± 8.5%, respectively. F-wave persistence was 100%. Mean F-wave duration was positively correlated with clinical grade of IVDH. Linear regression yielded the following regression equation: F-wave duration (milliseconds) = 6.0 + 2.7 × IVDH grade. One dog with grade 2 IVDH had a mean F-wave duration shorter than that of all 5 dogs with grade 1 IVDH; 1 dog with grade 3 IVDH had a longer duration than that of all 10 dogs with grade 4 IVDH. CONCLUSIONS AND CLINICAL RELEVANCE: Mean F-wave duration was correlated with the severity of inhibitory motor tract dysfunction in the spinal cord of dogs. F-wave examination may be useful for objective functional evaluation of upper motor neurons in the spinal cord.

Electroacupuncture improves neuronal function by stimulation of ascending peripheral nerve conduction in rats with spinal cord injury.

OBJECTIVE: To establish a method of transient sciatic nerve blockade and to examine the involvement of the ascending peripheral nerve pathway in the therapeutic effect of electroacupuncture at Zusanli (ST 36) in rats with spinal cord injury (SCI). METHODS: We examined the transient effect of daily lidocaine administration into the posteromedial part of the greater trochanter on sciatic nerve function using electrophysiological examination and histopathology of the sciatic nerve. Rats were divided into three groups: an SCI group (SCI without treatment), an SCI with electroacupuncture treatment (SCI-EA) group, and an SCI with nerve block and electroacupuncture (SCI-NB-EA) group (nerve block was achieved by lidocaine administration to transiently block the ascending peripheral nerve pathway). Behavioral tests and electrophysiological examinations were performed to evaluate recovery of neurological function. RESULTS: Sciatic nerve conduction was normal immediately before daily lidocaine administration. Histopathological analysis also indicated normal sciatic nerve, confirming that lidocaine nerve blockade was suitable and reversible for transiently eliminating nerve transmission. Neurological function in the SCI-EA group was superior to that in the SCI group, while no differences were found between the SCI and SCI-NB-EA groups. CONCLUSION: Electroacupuncture treatment can promote recovery of neurological function. Facilitation of nerve conduction may play an important role in this recovery.

Electrophysiological and histopathological findings of muscular disease suspected as myotonic dystrophy in a Shiba dog.

An 8-year-old male Japanese Shiba exhibited muscle wasting and a stiff gait. A low-amplitude myotonic discharge was recorded by needle electromyography (EMG). A histopathological examination on a tru-cut biopsy sample from the muscle revealed myofiber size variations. Internal nuclei and cytoplasmic vacuoles were observed in many fibers. A type 1 fiber predominance and many hybrid type fibers were observed immunohistochemically. On the basis of these EMG and histopathological findings, myotonic dystrophy (DM) was suspected as tentative diagnosis. The cytoplasm around the vacuoles was immunopositive for cytochrome c, tom 20, and SOD-1, suggesting that these vacuoles might occur within mitochondria. Collectively, these results indicate that a mitochondrial abnormality partly play the role on the pathogenesis of present case.

Establishment of a method to measure length of the ulnar nerve and standardize F-wave values in clinically normal beagles.

We designed a new method of measuring the length of the ulnar nerve and determining standard values for F-wave parameters of the ulnar nerve in clinically normal beagles. Nerve length must be precisely measured to determine F-wave latency and conduction velocity. The length of the forelimb has served as the length of the ulnar nerve for F-wave assessments, but report indicates that F-wave latency is proportional to the length of the pathway traveled by nerve impulses. Therefore, we measured the surface distance from a stimulus point to the spinous process of the first thoracic vertebra (nerve length 1) and the anterior horn of the scapula (nerve length 2) as landmarks through the olecranon and the shoulder blade acromion. The correlation coefficients between the shortest F-wave latency and the length of nerves 1, 2 or the forelimb were 0.61, 0.7 and 0.58. Nerve length 2 generated the highest value. Furthermore, the anterior horn of the scapula was easily palpated in any dog regardless of well-fed body. We concluded that nerve length 2 was optimal for measuring the length of the ulnar nerve.

F-wave conduction velocity, persistence, and amplitude for the tibial nerve in clinically normal cats.

OBJECTIVE: To establish a method of F-wave evaluation and to determine normative values of F-wave parameters, including F-wave conduction velocity, persistence, and amplitude for the tibial nerve in cats. ANIMALS: 30 clinically normal cats. PROCEDURES: F-waves elicited in the interosseous muscles by stimulation of the tibial nerve were recorded, and linear regression analyses of the shortest latency versus the length of the tibial nerve and the limb length were performed. F-wave persistence was calculated by dividing the number of recorded F-waves by the number of stimuli. RESULTS: The correlation coefficient between F-wave latency and nerve length was 0.92, and that between F-wave latency and limb length was 0.58. Mean +/- SD F-wave conduction velocity of the tibial nerve was calculated to be 97.1 +/- 5.0 m/s. Linear regression analysis yielded the regression equation as follows: F-wave latency (milliseconds) = 2.60 + (0.02 x nerve length [mm]). Mean F-wave persistence and amplitude were 98.7 +/- 2.3% and 1.01 +/- 0.62 mV, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that nerve length should be used for nerve conduction studies of F-waves in felids. The regression equation for F-wave latency, conduction velocity, persistence, and amplitude may contribute to the diagnosis of nervous system diseases or injury in cats, such as trauma to the spinal cord or diabetic neuropathy.

Clinicopathological features of canine neuroaxonal dystrophy and cerebellar cortical abiotrophy in Papillon and Papillon-related dogs.

Neuroaxonal dystrophy (NAD) was examined in two Papillon dogs and a mix breed dog between Papillon and Chihuahua. In addition, cerebellar cortical abiotrophy (CCA) in a Papillon dog, which had similar clinical and magnetic resonance imaging (MRI) features to those of NAD, was also investigated. The common clinical symptoms of all dogs affected with NAD and CCA, were pelvic limb ataxia and cerebellar ataxia including intention tremor, head tremor, and hypermetria in the early onset. These clinical signs were progressed rapidly, and two dogs with NAD were euthanized by owner's request and the other two died by aspiration pneumonia. MRI examinations and gross observations at necropsy revealed moderate to severe cerebellar atrophy in all cases of NAD and CCA. The most typical histological change of NAD was severe axonal degeneration with marked spheroid-formation in the dorsal horn of the spinal cords, the nuclei gracilis, cuneatus, olivalis and its circumference in the medulla oblongata. The spheroids were characterized as large eosinophilic or granular globes within the enlarged myelin sheaths, sometimes accompanied by moderate accumulation of microglias and/or macrophages. In contrast, such spheroid formation was minimal in the brain of CCA. In the cerebellum, mild to moderate loss of the Purkinje and granular cells were recognized in three dogs with NAD, whereas these changes were more prominent in a dog with CCA. Although the clinical signs and MRI findings relatively resembled between NAD and CCA, the histopathological features considered to be quite differ, suggesting distinct pathogenesis and etiology. Since both NAD and CCA are proposed as the autosomal recessive hereditary disorders, careful considerations might be needed for the breeding of Papillon and Chihuahua dogs.

Effectiveness of intraoperative somatosensory evoked potential monitoring during cervical spinal operations on animals with spinal cord dysfunction.

We conducted somatosensory evoked potential (SEP) monitoring on 3 dogs with cervical spinal cord dysfunction caused by various diseases throughout operative procedures to examine whether the intraoperative SEP monitoring was effective for prediction of spinal cord conductive function. The SEP was recorded on the scalp via stimulation of the ulnar nerve. Stable SEP was recorded in all animals examined. Its amplitude was decreased by surgical manipulations of the regio vertebralis, but the amplitude gradually recovered once the manipulations were halted. The latency showed small variation throughout the operations. This evidence suggests that intraoperative SEP monitoring may provide continuous and instantaneous information regarding the functional integrity of the central nervous system.

Usefulness of combined electrophysiological examinations for detection of neural dysfunction in cats with lumbar hematomyelia.

We conducted combined electrophysiological examinations including F-wave, motor nerve conduction velocity (MNCV), spinal cord-evoked potential (SCEP), and needle electromyography (EMG) in two cats involved in traffic accidents that consequently developed hind limb paralysis caused by lumbar hematomyelia. F-wave could no longer be elicited within 3 days after the accident, and the MNCV and compound muscle action potential (CMAP) amplitude decreased in a time-dependent manner, with CMAP no longer being evoked after 7 or 8 days. EMG showed abnormalities such as fibrillation and positive sharp waves after 6 to 8 days. These results suggest that such combined electrophysiological examinations may provide objective, quantitative data for motor nerve dysfunction in cats with lumbar hematomyelia.

F-wave latency and F-wave conduction velocity for the tibial nerve in clinically normal dogs.

OBJECTIVE: To establish a method of F-wave examinations and to determine values of F-wave conduction velocity (FWCV) and F-wave latency for the tibial nerve of clinically normal dogs. ANIMALS: 21 clinically normal dogs. PROCEDURE: The F-waves were elicited from the interosseous muscles via stimulation of the tibial nerve. The FWCV was determined by using the F-wave shortest value and the surface distance corresponding to the tibial nerve length. Correlation between the smallest latency value of the F-wave and the length of the tibial nerve and between the FWCV and rectal temperature were closely examined. RESULTS: F-wave latency was proportional to the length of the tibial nerve (correlation coefficient, 0.929). Mean +/- SD FWCV was 77.98 +/- 8.62 m/s. Regression equation was as follows: F-wave latency = 2.799 + (0.029 X length of the tibial nerve). The FWCV was increased when the measured rectal temperature was high. Correlation coefficient between FWCV and rectal temperature was 0.665. CONCLUSIONS AND CLINICAL RELEVANCE: In the study reported here, we established a reliable method for clinical evaluation of the F-wave. When assessing nerve conduction velocity, it is essential to measure nerve length along the pathway that the nerve impulse travels. This method of F-wave examination is a useful diagnostic tool for the evaluation of suspected dysfunction of the peripheral nervous system.