Metronidazole-induced neurotoxicity in 26 dogs.

BACKGROUND: Metronidazole is an antibacterial, antiprotozoal and anthelmintic medication commonly used in veterinary medicine. We describe cases of neurotoxicity associated with the drug's administration. METHODS: Medical records between 2004 and 2017 from four veterinary referral hospitals were reviewed. Inclusion criteria were the presence of neurological signs compatible with metronidazole toxicity, clinical history supporting recent metronidazole therapy and resolution of clinical signs upon discontinuation of metronidazole administration. RESULTS: A total of 26 dogs were identified with clinical signs supporting a diagnosis of metronidazole toxicity. Median age at presentation was 7.2 years (range, 0.1-12 years); median duration of treatment was 35 days (range, 5-180 days); median treatment dosage was 21 mg/kg BID (range, 13-56 mg/kg every 12 h); median resolution of the clinical signs upon discontinuation of metronidazole was 3 days (range, 1-26 days). Magnetic resonance imaging (MRI) of the brain was performed in 19 cases and only one dog had brain lesions affecting the dentate nuclei, which resembled the MRI appearance of this disease in humans. CONCLUSIONS: We found evidence of neurotoxicity in dogs at much lower doses than previously reported and we suggest caution when administering metronidazole at doses > 40 mg/kg every 24 h, regardless of the duration of the treatment.

Dorsal laminectomy for treatment of cervical vertebral stenotic myelopathy in an alpaca.

CASE DESCRIPTION: An 11-year-old male breeding alpaca was evaluated for a 2-day history of lowered head carriage and lethargy. CLINICAL FINDINGS: On initial examination, the alpaca had signs of lethargy and lowered carriage of the head and neck, but no specific neurologic deficits. Medical management improved the clinical signs, but 8 months later, the alpaca developed acute, progressive general proprioceptive ataxia affecting all 4 limbs and was referred for further evaluation and treatment. Magnetic resonance imaging and CT identified disruption of the normal osseous architecture of C7 and T1. Medical management was attempted, but because of a lack of improvement, the patient underwent surgery 14 months after initial examination. TREATMENT AND OUTCOME: A dorsal laminectomy of C7 and T1 via a dorsal midline approach was performed, and the spinous processes of both vertebrae were removed prior to removal of the overlying lamina. Free dorsal expansion of the spinal cord was ensured by resection of the ligamentum flavum. Six months after surgery, the alpaca had returned to successful breeding with 7 hembra bred in the first year after surgery, producing 6 crias, and 4 crias in the second year. The patient was eventually euthanized 28 months after surgery because of neurologic deterioration but was still ambulatory at that time. CONCLUSIONS AND CLINICAL RELEVANCE: A good outcome with adequate alleviation of clinical signs and breeding soundness for > 2 years following dorsal laminectomy was achieved in this camelid patient. The surgical approach was similar to that in other species and was associated with mild postoperative morbidity. Veterinarians treating camelids should be aware of the initial clinical signs and treatment options for cervical vertebral stenotic myelopathy. In acute cases, the signs of reduced cervical mobility and pain on manipulation should prompt investigation including appropriate diagnostic imaging. Timely surgical intervention should be considered in patients that respond poorly to medical treatment to avoid irreversible spinal cord injury and optimize outcome.

An update on the pathogenesis of syringomyelia secondary to Chiari-like malformations in dogs.

Syringomyelia (SM) is a spinal cord disease that can cause neuropathic pain in dogs. The pathogenesis of SM secondary to Chiari-like malformation (CM) has been the focus of intense research in recent years. The gulf in our understanding of CM/SM in dogs relative to the analogous human condition has progressively narrowed. CM is primarily a disease of abnormal geometric morphometry affecting the caudal cranial fossa and the brain parenchyma contained within it. This review describes how advanced imaging techniques have revealed a series of morphometric abnormalities associated with CM/SM. The series is presented in a logical order to help describe the pathogenesis of CM and the subsequent formation of syringes, with particular reference to the concepts of craniospinal compliance and cerebrospinal fluid pulse pressure timing.

Assessment of cerebellar pulsation in dogs with and without Chiari-like malformation and syringomyelia using cardiac-gated cine magnetic resonance imaging.

Canine Chiari-like malformation (CM) is characterised by herniation of part of the cerebellum through the foramen magnum. In humans with Chiari type I malformation (CM-I), abnormal pulsation of the cerebellum during the cardiac cycle has been documented and is pivotal to theories for the pathogenesis of syringomyelia (SM). In this retrospective study, cardiac-gated cine balanced fast field echo (bFEE) magnetic resonance imaging (MRI) was used to assess pulsation of the brain in dogs and to objectively measure the degree of cerebellar pulsation with the neck in a flexed position. Overall, 17 Cavalier King Charles Spaniels (CKCS) with CM, including eight with SM and nine without SM, were compared with six small breed control dogs. Linear regions of interest were generated for the length of cerebellar herniation from each phase of the cardiac cycle and the degree of cerebellar pulsation was subsequently calculated. Age, bodyweight and angle of neck flexion were also compared. CKCS with CM and SM had significantly greater pulsation of the cerebellum than control dogs (P=0.003) and CKCS with CM only (P=0.031). There was no significant difference in age, bodyweight and angle of neck flexion between the three groups. Cardiac-gated cine bFEE MRI permitted the dynamic visualisation of cerebellar pulsation in dogs. These findings support the current theories regarding the pathogenesis of SM secondary to CM and further highlight the similarities between canine CM and human CM-I.

The association between Chiari-like malformation, ventriculomegaly and seizures in cavalier King Charles spaniels.

Cavalier King Charles spaniels (CKCSs) with Chiari-like malformation (CM) and associated seizures are frequently diagnosed with idiopathic epilepsy. There could be an association between ventriculomegaly (V) or caudal fossa overcrowding (CCFP) and seizures. A retrospective case-control study was performed using MRI to investigate the possible association between these morphological abnormalities and seizures. Seizure semiology and, where possible, electroencephalographic (EEG) abnormalities were documented. Eighty-five CKCS with CM were included, 27 with seizures. There was no association between V or CCFP and seizures (P=0.10 and 0.71, respectively). Seizures were classified as having partial onset in 61% of individuals in the study population (95% CI 42.41-76.43%). Another cause of recurrent seizures in CKCS (such as familial epilepsy) is suspected, as previously reported.

Intra-abdominal blockage of a ventriculoperitoneal shunt by a suspected mesenteric pseudocyst in a dog.

BACKGROUND: There are few reports of abdominal complications following ventriculoperitoneal (VP) shunt placement for the treatment of hydrocephalus in dogs. CASE REPORT: A 3-year-old dog underwent successful VP shunting for the treatment of hydrocephalus, but re-presented 10 months later with progressive central vestibular syndrome. Magnetic resonance imaging of the brain suggested VP catheter obstruction. The dog was euthanased and on postmortem examination the abdominal tip of the VP catheter was ensheathed and blocked by fibrous mesentery, possibly a pseudocyst. CONCLUSIONS: Abdominal complications are common in humans, with pseudocysts reported in up to 4.5% of cases. This diagnosis should be considered for dogs re-presenting following VP shunt surgery.

Long-term outcome of Cavalier King Charles spaniel dogs with clinical signs associated with Chiari-like malformation and syringomyelia.

The disease complex Chiari-like malformation (CM) and syringomyelia (SM) has been associated with the development of neuropathic pain (NeP), and commonly affects Cavalier King Charles spaniels (CKCS). This prospective cohort study followed 48 CKCSs with CM and/or SM and clinical signs suggestive of NeP for a period of 39 (±14.3) months from diagnosis. At the end of the study, 36 dogs were still alive; five dogs died of an unrelated or unknown cause, and seven were euthanased due to severe clinical signs suggestive of NeP. During the follow-up period, the clinical signs of scratching, facial rubbing behaviour, vocalisation and exercise ability were evaluated. Nine out of 48 dogs stopped scratching (P<0.001), but there was no statistically significant change in the number of dogs exhibiting exercise intolerance, vocalisation or facial rubbing behaviour. The overall severity of clinical signs based on a visual analogue scale (VAS) (0 mm: no clinical signs 100 mm: severe clinical signs) increased (from median 75 mm (interquartile ranges (IQR) 68-84) to 84 mm (IQR 71.5-91), P<0.001). A quarter of the dogs were static or improved. In general, the majority of the owners felt that the quality of life of their dogs was acceptable. Medical treatments received were gabapentin or pregabalin and/or intermittently, carprofen. The owner's perception of their animal's progress, and progress based on VAS, had strong positive correlation (Spearman's rank correlation (s(r)) 0.74, P<0.001). Overall, this study suggests that clinical signs suggestive of NeP progress in three-quarters of CKCSs with CM and/or SM.

Influence of head positioning on the assessment of Chiari-like malformation in Cavalier King Charles spaniels.

Chiari-like malformation (CM) is almost omnipresent in the Cavalier King Charles spaniels (CKCS), often leading to syringomyelia (SM). Morphometric studies have produced variable results concerning relationship between the brain parenchyma within the caudal cranial fossa (CCF) and SM. The present study assesses the effect of head position, one potential confounder. Magnetic resonance images of CKCS with CM were reviewed in extended and flexed head positions. Volumes were calculated from transverse T2-weighted brain images. Mid-sagittal images were used for measurement of cerebellar herniation and CSF space between cerebellum and brainstem. Fourteen CKCS were included into the study, seven dogs with CM and seven with CM/SM. There was no difference between the relative brain parenchyma within the CCF in extended position and flexed position, or the brain parenchyma within the rostral and middle cranial fossae proportion. Cerebellar herniation and CSF space between cerebellum and brainstem were significantly increased in the flexed position. Cerebellar herniation and CSF space differed significantly between CM and CM/SM in a flexed head position. Volumetric measurements did not vary with head position. Cerebellar herniation and CSF space between the cerebellum and the brainstem were larger in a flexed head position.

Relationship of brain parenchyma within the caudal cranial fossa and ventricle size to syringomyelia in cavalier King Charles spaniels.

OBJECTIVES: To assess if the volumes of the caudal cranial fossa (CCF), parenchyma within the caudal cranial fossa (CCFP) or ventricles (V) are associated with syringomyelia (SM) in cavalier King Charles spaniels (CKCS) with Chiari-like malformation (CM). To evaluate if volumes are associated with transverse syrinx width. METHODS: Magnetic resonance images of 59 CKCS with CM were retrospectively reviewed and grouped with or without SM. Three-dimensional images were created and volumes of the fossae, brain parenchyma and ventricular system were calculated from which percentages of CCF, CCFP and V were created. If present, syrinx size was measured from its maximal transverse width. The percentages were statistically compared between groups, and correlation between percentages and syrinx dimensions was made. RESULTS: CKCS with SM had significantly higher CCFP (P=0.0001) and V (P=0.0002) to those without but no significant difference in CCF (P=0.925). There was a positive correlation between CCFP and syrinx width (Pearson r=0.437) and ventricle size to syrinx width (Spearman r=0.627). CLINICAL SIGNIFICANCE: A more marked overcrowding of the CCF is associated with SM, which may explain the high incidence of SM in CKCS with CM. The association between ventricle and syrinx dimensions supports the theory that SM development is the result of altered cerebrospinal fluid dynamics.

Apparent retardation of aging in Drosophila melanogaster by inhibitors of reverse transcriptase.

It is proposed that aging is induced by somatic replication of transposable elements (TEs). Most transposable elements in Drosophila reproduce by reverse transcription. Therefore inhibitors of reverse transcriptase were tested for their ability to retard aging in Drosophila melanogaster. Two inhibitors, phosphonoformic acid (PFA) and dideoxyinosine (ddI), were capable of prolonging life span when administered for the first half of the adult life. PFA was investigated further. It also produced a reduction in the rate of decline of behavior. PFA appeared not to act on an infectious agent in these experiments, nor did it alter the food intake. Analogues unable to inhibit RT had no life span prolonging effect at similar concentrations to that of PFA.

Transposable elements as a factor in the aging of Drosophila melanogaster.

We have considered the hypothesis that transposable elements may contribute to the aging process through somatic mutation. We have presented evidence to suggest that at least two elements, Copia and 412, are capable of somatic activity in adult Drosophila tissue. A strain harboring a third transposable element, P, was produced that showed eye color mosaicism and reversion to wild phenotype (red eyes) as a result of somatic and germ line transposition. A high-fat diet, known to accelerate aging, increased the frequency of eye color mosaicism and red eyes. We induced life span shortening by artificially activating somatic transposition of P elements, and the extent of reduction in life span was similar in both sexes. These data are consistent with the notion that some aspects of the age phenotype may be caused by mutational activity of transposable elements in somatic tissues. The hypothesis is readily tested in other organisms, including humans. It offers new dimensions in the understanding and management of age-associated changes.

The effect of meal composition on the degree of satiation following a test meal and possible mechanisms involved.

1. Possible links between metabolism and satiation were investigated using volunteer subjects given test meals based on milk solids. Satisfaction was rated by the subjects on a six-point scale and the course of metabolism was followed by measurement of the respiratory quotient (RQ). 2. The time-course of satiation was the same for a high-carbohydrate, a high-fat and a high-protein meal, in spite of the very different time-course of metabolism. The degree of satiation was reduced by added sodium chloride, without affecting the RQ rise. On the other hand, calcium chloride produced a suppression of the RQ rise without altering the satiation. 3. It is proposed that the results indicate that the primary receptors responsible for post-prandial satiation lie within the gut wall and that there is probably a number of receptor types. Likely candidates for these receptors are the gut hormone-secreting cells. 4. Although very-low-protein meals produce less satiation than meals containing 220 g protein/kg dry weight, there is no additional satiation obtained by increasing the protein level further. This is not inconsistent with the possibility of a protein hunger separate from an energy hunger.

Is a fat metabolite the major diet dependent accelerator of aging?

Previous work with a high fat/low carbohydrate diet indicated that Drosophila melanogaster aged faster on that diet than on a high carbohydrate/low fat diet. This could be due to one of eight possibilities enumerated. Oxygen consumption of flies on the high fat/low carbohydrate diet is initially the same as that on the control diet. Subsequently the oxygen consumption falls to below control levels at older ages. No increased rate of living is indicated. A starvation resistant strain is described. The male eats less food, and yet maintains a body fat level indistinguishable from the parent strain. The lifespan and most physiological indices of aging used indicate that the process of aging is unchanged. Nutrient dilution produces a nearly compensatory increase in food intake with a reduced body fat and body energy reserves. The indices of aging used indicate that the rate of aging is reduced under these circumstances. These results are consistent with the possibility that fat or a fat metabolite alters the rate of aging. It is argued from previous data that body fat itself is not likely to be the important factor, rather a metabolite is probably involved.

The effect of methyl parathion on susceptibility of bobwhite quail (Colinus virginianus) to domestic cat predation.

Bobwhite quail (Colinus virginianus) that received either 0, 2, 4, or 8 mg/kg methyl parathion (O,O-dimethyl o-p-nitrophenyl phosphorothioate) treatment were investigated as to their susceptibility to predation by a cat (Felis domesticus) predator. Four hours after receiving methyl parathion (MP), physical activity levels were monitored in quail and included the number of seconds spent still, walking, running, or flying before and after a cat was introduced into an experimental arena. The cholinesterase (ChE) activity for each quail on experiment was determined. Quail that were captured exhibited significantly greater inhibition of brain ChE activity and spent significantly more time being still than noncaptured birds. Birds receiving MP at 8 mg/kg spent more seconds being still than those in other treatment groups and had ChE activity reduced to 42.8% of normal activity. There was a tendency for quail at increasing treatment levels to be more susceptible to capture by the cat predator. The neurological and behavioral effects of methyl parathion may have important ecological ramifications.