Association between estrus and onset of seizures in dogs with idiopathic epilepsy.

BACKGROUND: Catamenial epilepsy in humans is defined as changes in seizure frequency over the course of the menstrual cycle. Three hormonally based patterns of seizure exacerbation have been determined. OBJECTIVES: The aim of this study was to evaluate whether there is an association between onset of seizures and the estrous cycle in intact bitches with presumptive idiopathic epilepsy and whether a pattern to the onset of seizures could be recognized. ANIMALS: Forty-five intact female dogs from a hospital population with a presumptive diagnosis of idiopathic epilepsy. METHODS: In a retrospective study, the database of a small animal hospital in Sweden was searched for medical records of intact female dogs diagnosed with epilepsy or seizures. The stage of the estrous cycle as reported either by the owner or the veterinarian at the time of the first seizure was noted. RESULTS: Of the 45 dogs with idiopathic epilepsy, 17 (38%) had their first seizure when in heat and six dogs (13%) had their first seizure 1-3 months after heat. Nine dogs (20%) had seizures reoccurring in relation to their estrous cycle. CONCLUSIONS AND CLINICAL IMPORTANCE: These findings suggest an association between estrus and onset of seizures in intact bitches with presumptive idiopathic epilepsy. Two hormonally based patterns could be recognized: one during heat and one during a specific time point at the end of diestrus. This could be explained by the proconvulsive effects of estrogen or loss of protective effect against seizures of progesterone, respectively.

Comparison between symptomatic treatment and lomustine supplementation in 71 dogs with intracranial, space-occupying lesions.

Brain neoplasia is diagnosed in an increasing number of dogs. Consequently, there is a higher need for an effective treatment. Chemotherapy is considered in cases where surgery or radiation is not optional. The objective of this retrospective study was to evaluate the difference in median survival time (MST) of dogs with intracranial masses, treated symptomatically with corticosteroids and anti-epileptic drugs, compared with the same symptomatic treatment supplemented with lomustine. The records of 71 dogs with intracranial masses were retrospectively evaluated. Fifteen dogs were treated symptomatically with corticosteroids and anti-epileptics, and 56 dogs received additional therapy with lomustine. There was no statistically significant difference in MST between both groups, being 60 and 93 days, respectively. Age, duration of symptoms, intracranial localization of the mass and intra- or extra-axial localization had no influence on survival time. However, female dogs survived significantly longer than male dogs.

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.

Current insights and controversies in the pathogenesis and diagnosis of disc-associated cervical spondylomyelopathy in dogs.

Disc-associated cervical spondylomyelopathy (DA-CSM) is the most common cause of cervical spondylomyelopathy in dogs. In this condition, progressive caudal cervical spinal cord compression is typically caused by protrusion of one or more intervertebral discs. This disc-associated compression is sometimes seen in combination with mild vertebral abnormalities and dorsal compression resulting from ligamentum flavum hypertrophy. The intervertebral disc space between the sixth (C6) and seventh (C7) cervical vertebrae is most commonly affected. Although several large breed dogs can be affected, the adult to older dobermann is overrepresented. Clinical signs vary from cervical hyperaesthesia to tetraplegia. Dogs can present with a chronic progressive or an acute onset of clinical signs. Many aspects of this multifactorial neurological syndrome are not completely understood and are the subject of controversy and debate. Although several factors have been proposed, the underlying pathology and aetiology remain unknown. Recently, new insights have been gained in the pathogenesis, diagnosis and treatment of this challenging neurological syndrome. This review outlines current controversies and new developments concerning the pathogenesis and diagnosis of DA-CSM.

Bilateral obturator neuropathy caused by an intrapelvic fibrosarcoma with myofibroblastic features in a dog.

A nine-year-old female Rottweiler presented with a 6-week history of progressive impairment of hindlimb adduction. Clinical examination showed abduction of both hind legs when walking on a smooth surface, pain at the medial surface of the left thigh, and an intrarectal palpable mass at the pelvic floor. Electromyography demonstrated fibrillation potentials in the adductor muscles on both sides. Pelvic radiographs showed severe osteolysis of the ischium. Gross post-mortem examination following euthanasia disclosed a large retroperitoneal mass, invading the obturator foramina and compressing both obturator nerves. Histopathological examination revealed a high-grade anaplastic sarcoma. Immunohistochemically, the tumour cells labelled positively for vimentin and alpha-smooth muscle actin, hence the tumour was considered a "myofibroblastic fibrosarcoma". This unique case report describes a novel cause of obturator neuropathy in veterinary medicine. To date, clinical descriptions of obturator nerve lesions have been limited to pelvic fractures in small animals and following difficult labour in large animals.

Neuromyotonia in a dachshund with clinical and electrophysiological signs of spinocerebellar ataxia.

A 10-month-old dachshund was presented with a recent history of episodic muscle rippling and generalised stiffness. An uncoordinated gait was present since eight weeks of age. On presentation the dog showed cerebellar-like ataxia and poor menace responses. Myokymic contractions were visible in the appendicular and truncal muscles and neuromyotonic discharges were detected by electromyography. Central components of the brain auditory evoked potentials were absent and the onset latencies of the tibial sensory-evoked potentials recorded at the lumbar intervertebral level were delayed. Response to slow-release phenytoin was temporary. The clinical picture together with the electrophysiological findings in this dachshund are identical to the findings in Jack Russell terriers with hereditary ataxia and neuromyotonia. This is the first description of neuromyotonia associated with clinical and electrophysiological signs of spinocerebellar ataxia in a breed other than the Jack Russell terrier. This case also strengthens the theory that spinocerebellar ataxia and neuromyotonia are related. An ion channel dysfunction is presumed to link both disorders.

Muscle potentials evoked by magnetic stimulation of the sciatic nerve in unilateral sciatic nerve dysfunction.

Magnetic stimulation of the sciatic nerve and subsequent recording of the muscle-evoked potential (MEP) was performed in eight dogs and three cats with unilateral sciatic nerve dysfunction. Localisation of the lesion in the sciatic nerve was based on the history, clinical neurological examination and on results of electromyography examination. Aetiology of the sciatic nerve lesion was diverse. A significant difference was found in MEP between the normal and the affected limbs. In addition, absence of conscious pain sensation, absence of voluntary motor function and a poor outcome seemed associated with the inability to evoke an MEP in the affected limb.

Inspiratory stridor secondary to palatolingual myokymia in a Maltese dog.

A nine-year-old male Maltese dog was presented with an eight-month history of inspiratory stridor leading to exertional dyspnoea and cyanosis. Myokymic contractions in the palatolingual muscles were noticed and confirmed by electromyography. Brain computer tomography-scan showed ventricular dilatation. Cerebrospinal fluid analysis revealed a slightly elevated protein level. Treatment with slow-release phenytoin was unsuccessful and symptoms gradually worsened over the next nine months. At post-mortem examination a small pituitary adenoma was found. Apart from a single canine report of facial myokymia, this is the only other description of spontaneous focal myokymia in animals. Palatolingual myokymia has only been reported in one human being. Although the co-occurrence with a pituitary adenoma might be incidental, a paraneoplastic pathogenetic mechanism is proposed. Its unique clinical presentation adds a new, albeit uncommon, syndrome to the differential diagnosis of upper airway complaints in dogs.

Clinical evaluation of 51 dogs treated conservatively for disc-associated wobbler syndrome.

OBJECTIVES: To evaluate the clinical evolution and potential risk factors of 51 dogs treated conservatively for disc-associated wobbler syndrome. METHODS: Medical records of dogs treated conservatively for disc-associated wobbler syndrome were reviewed, and owners were contacted regarding clinical evolution and survival of their animals. Relationships between age, treatment before diagnosis, type of neurological signs, results of medical imaging and outcome were determined. RESULTS: Fifty-one dogs underwent conservative treatment for disc-associated wobbler syndrome. A successful outcome was achieved in 45 per cent (23 of 51) of the patients. Median follow-up period was 18.5 months, and median survival time was 47 months. In 85 per cent of the dogs in which euthanasia was performed because of disc-associated wobbler syndrome, this was carried out in the first year after diagnosis. Outcome score was influenced by type of neurological signs and additional radiographic and/or myelographic abnormalities. Outcome score was not significantly associated with age, number of protruded intervertebral discs, occurrence, type and results of treatment before diagnosis. CLINICAL SIGNIFICANCE: Conservative treatment of disc-associated wobbler syndrome is associated with a guarded prognosis. It can be considered in cases where all four limbs are not affected and no additional radiographic and/or myelographic abnormalities are detected.

Hemifacial spasm associated with an intracranial mass in two dogs.

Two dogs were presented with hemifacial spasm. Computed tomography images of both the dogs revealed an intracranial mass. In the first dog, a lesion at the level of the medulla oblongata was thought to cause primary irritation of the facial nucleus, with consequently permanent contraction of the ipsilateral facial muscles. In the second dog, a mass seemingly arising from the middle cranial fossa presumably isolated the facial motor neurons from upper motor neuron control, which resulted in hemifacial spasm as a result of loss of inhibitory interneuronal activity.

Adenohypophyseal function in bitches treated with medroxyprogesterone acetate.

The aim of this study was to investigate the effects of treatment with medroxyprogesterone acetate (MPA) on canine adenohypophyseal function. Five Beagle bitches were treated with MPA (10mg/kg, every 4 weeks) and their adenohypophyseal function was assessed in a combined adenohypophyseal function test. Four hypophysiotropic hormones (CRH, GHRH, GnRH, and TRH) were administered before and 2, 5, 8, and 11 months after the start of MPA treatment, and blood samples for determination of the plasma concentrations of ACTH, cortisol, GH, IGF-1, LH, FSH, prolactin, alpha-MSH, and TSH were collected at -15, 0, 5, 10, 20, 30, and 45 min after suprapituitary stimulation. MPA successfully prevented the occurrence of estrus, ovulation, and a subsequent luteal phase. MPA treatment did not affect basal and GnRH-induced plasma LH concentrations. The basal plasma FSH concentration was significantly higher at 2 months after the start of MPA treatment than before or at 5, 8, and 11 months after the start of treatment. The maximal FSH increment and the AUC for FSH after suprapituitary stimulation were significantly higher before treatment than at 5, 8, and 11 months of MPA treatment. Differences in mean basal plasma GH concentrations before and during treatment were not significant, but MPA treatment resulted in significantly elevated basal plasma IGF-1 concentrations at 8 and 11 months. MPA treatment did not affect basal and stimulated plasma ACTH concentrations, with the exception of a decreased AUC for ACTH at 11 months. In contrast, the maximal cortisol increment and the AUC for cortisol after suprapituitary stimulation were significantly lower during MPA treatment than prior to treatment. MPA treatment did not affect basal plasma concentrations of prolactin, TSH, and alpha-MSH, with the exception of slightly increased basal plasma TSH concentrations at 8 months of treatment. MPA treatment did not affect TRH-induced plasma concentrations of prolactin and TSH. In conclusion, the effects of chronic MPA treatment on adenohypophyseal function included increased FSH secretion, unaffected LH secretion, activation of the mammary GH-induced IGF-I secretion, slightly activated TSH secretion, suppression of the hypothalamic-pituitary-adrenocortical axis, and unaffected secretion of prolactin and alpha-MSH.

Treatment of growth hormone excess in dogs with the progesterone receptor antagonist aglépristone.

Acromegaly or hypersomatotropism in dogs is almost always due to progestin-induced hypersecretion of GH originating from the mammary gland. The aim of this study was to investigate whether aglépristone, a progesterone receptor antagonist, can be used to treat this form of canine acromegaly. In five Beagle bitches hypersomatotropism was induced by administration of MPA for over 1 year. Subsequently, aglépristone was administered. Blood samples were collected before MPA administration, immediately before, during, and 3.5 and 5.5 weeks after the last administration of aglépristone for determination of the plasma concentrations of GH and IGF-I. In addition, blood samples for the determination of the 6-h plasma profile of GH were collected before MPA administration, before aglépristone administration, and 1 week after the last aglépristone treatment. MPA administration resulted in a significant increase of the mean plasma IGF-I concentration, whereas analysis of the pulsatile plasma profile demonstrated a trend (P=0.06) for a higher mean basal plasma GH concentration and a higher mean AUC(0) for GH. Treatment with aglépristone resulted in a significant decrease of the mean plasma GH and IGF-I concentrations. Analysis of the pulsatile plasma profile showed a trend (P=0.06) for a lower mean basal plasma GH concentration and a lower mean AUC(0) for GH 1 week after the last aglépristone treatment compared with these values before aglépristone administration. Three and a half and 5.5 weeks after the last aglépristone administration the mean plasma IGF-I concentration increased again. In conclusion, aglépristone can be used successfully to treat dogs with progestin-induced hypersomatotropism.

Ghrelin-stimulation test in the diagnosis of canine pituitary dwarfism.

This study investigated whether ghrelin, a potent releaser of growth hormone (GH) secretion, is a valuable tool in the diagnosis of canine pituitary dwarfism. The effect of intravenous administration of ghrelin on the release of GH and other adenohypophyseal hormones was investigated in German shepherd dogs with congenital combined pituitary hormone deficiency and in healthy Beagles. Analysis of the maximal increment (i.e. difference between pre- and maximal post-ghrelin plasma hormone concentration) indicated that the GH response was significantly lower in the dwarf dogs compared with the healthy dogs. In none of the pituitary dwarfs, the ghrelin-induced plasma GH concentration exceeded 5 microg/l at any time. However, this was also true for 3 healthy dogs. In all dogs, ghrelin administration did not affect the plasma concentrations of ACTH, cortisol, TSH, LH and PRL . Thus, while a ghrelin-induced plasma GH concentration above 5 microg/l excludes GH deficiency, false-negative results may occur.

Sufentanil and nitrous oxide anaesthesia for the recording of transcranial magnetic motor evoked potentials in dogs.

Transcranial magnetic motor evoked potentials were recorded from the extensor carpi radialis muscle of the forelimbs and from the cranial tibial muscle of the hindlimbs of anaesthetised dogs. The dogs were premedicated with droperidol and fentanyl and a light plane of anaesthesia was induced and maintained with sufentanil and nitrous oxide. The potentials recorded under sufentanil and nitrous oxide anaesthesia were suppressed in comparison with baseline recordings under droperidol and fentanyl sedation: their latencies were significantly increased and their amplitudes significantly decreased (P < 0.05). However, the potentials could be recorded reliably in all the dogs and with very good reproducibility. This narcotic anaesthesia also allowed sensory evoked potentials to be recorded reliably.

Comparison of two techniques of narcotic-induced anesthesia for use during recording of magnetic motor evoked potentials in dogs.

OBJECTIVE: To compare 2 types of narcotic-induced anesthesia for recording of transcranial magnetic motor evoked potentials (TMMEP) in dogs. DESIGN: The effect of different doses of sufentanil and midazolam and of sufentanil and nitrous oxide on onset latencies and peak-to-peak, amplitudes of TMMEP was evaluated and compared. ANIMALS: 18 neurologically normal dogs. PROCEDURE: Premedication with droperidol and fentanyl. Induction and maintenance of anesthesia either with sufentanil and midazolam or with sufentanil and nitrous oxide. Recording of TMMEP from the extensor carpi radialis muscle of the forelimb and from the cranial tibial muscle of the hind limb. RESULTS: Both types of narcotic anesthesia induced dose-dependent suppression of TMMEP; compared with baseline recordings, latencies increased, amplitudes decreased, and reproducibility became poorer with increasing dose of the anesthetics. Using surgical-depth doses of the anesthetics, TMMEP could still be recorded in all dogs with sufentanil and nitrous oxide, but not with sufentanil and midazolam anesthesia. CONCLUSIONS: Sufentanil and nitrous oxide anesthesia was superior to sufentanil and midazolam anesthesia for TMMEP recording. CLINICAL RELEVANCE: In small animal medicine, and in dogs in particular, spinal cord diseases are among the most frequently encountered neurologic disorders. The development of techniques for recording TMMEP in anesthetized dogs allows noninvasive evaluation of transmission along descending motor pathways of the spinal cord.

Molecular analysis and nucleotide sequence of finQ, a transcriptional inhibitor of the F plasmid transfer genes.

We report the cloning of finQ, a gene coding for fertility inhibition of the F plasmid, from the IncI R factor R820a. The finQ gene was mapped precisely within a 1.24 kb region by ptac-transposase + min-kan mutagenesis and its product, FinQp, identified as a single polypeptide by means of SDS-polyacrylamide gel electrophoresis. Nucleotide sequencing of the finQ region allowed elucidation of the FinQp amino acid sequence and determination of its precise molecular weight as 39,895 Da. Analysis of the predicted amino acid sequence indicated that FinQp is a positively charged protein possessing a helix-turn-helix DNA binding motif. We propose a possible model for the mechanism by which FinQp terminates transcription within the F plasmid tra region. DNA-DNA hybridization established that all FinQ+ R factors examined have an homologous finQ gene.

Transcriptional analysis of the F plasmid surface exclusion region: mapping of traS, traT, and traD transcripts.

Transcription of the surface exclusion genes, traS and traT, of the F plasmid of Escherichia coli K-12 has been analyzed using S1 nuclease protection experiments. The results show that both genes possess functional promoters in vivo and that a strong transcriptional termination signal lies immediately downstream of traT. Moreover, the adjacent downstream gene, traD, is expressed from its own promoter and appears not to lie within the major transfer operon. RNA stability experiments indicate that the products of traS and traT are translated from a stable RNA message. We propose that the traS and traT promoters serve to supplement the expression of these genes from the major tra promoter, PY.

Nucleotide sequence of the F plasmid transfer gene, traH: identification of a new gene and a promoter within the transfer operon.

The nucleotide sequence of the F plasmid transfer gene traH, which is involved in F-pilus assembly in Escherichia coli K-12, has been determined. From the sequence data, it would appear that traH encodes a 38,897-dalton precursor polypeptide which is processed to give a periplasmic protein. Furthermore, a new gene, trbF, has been located immediately upstream of traH and shown to be expressed by means of a translational fusion to lacZ. Using galK fusion and S1 nuclease protection studies, a weak traJ-dependent promoter, P trbF, has been mapped upstream and adjacent to trbF. Transcription of trbF and traH from P trbF may well serve to complement transcription from the major tra operon promoter PY located some 16 kb upstream of these genes.

Surface exclusion genes traS and traT of the F sex factor of Escherichia coli K-12. Determination of the nucleotide sequence and promoter and terminator activities.

The DNA encoding the surface exclusion genes traS and traT of the F sex factor of Escherichia coli K-12 has been sequenced and the biological activity of the various terminators and promoters determined. The data show that traS encodes a 16,861 Mr protein with no apparent signal sequence, as expected for its cytoplasmic membrane location. The protein is extremely hydrophobic. traS has its own promoter and a weak terminator region follows the gene. After the traS termination loop there is a small intergenic region before the traT promoter. The traT gene encodes a 25,932 Mr precursor for the 23,709 Mr mature protein. The amino-terminal signal peptide is 21 amino acid residues, consistent with it being an outer membrane lipoprotein. A very strong termination loop follows the gene and adjacent to this a further loop can be predicted from the sequence. These secondary structures would be expected to enhance the stability of the mRNA in the presence of 3' specific ribonucleases accounting for the apparent long half-life of the messenger. The amino acid sequence of the mature product of traT of F differs from that of R100 by only a single amino acid substitution (Gly for Ala at position 119), whereas that of pED208 (Folac) differs at 40 positions. traT lies in a region of heteroduplex homology between F and R100, and the nucleotide sequence confirms this and demonstrates that this homology breaks down immediately preceding and following the coding region. Sequence analysis shows that this is also so for pED208. Thus the entire traS of F, R100 and pED208 are very different at the DNA level. An open reading frame, preceded by a typical promoter sequence and a weak and poorly located Shine-Dalgarno sequence, follows traT and corresponds to the start of traD. Alone, this promoter appears to be inactive.