George M. Strain

Aetiology, prevalence and diagnosis of deafness in dogs and cats.

Peripheral deafness may be inherited or acquired, congenital or later-onset, and sensorineural or conductive. The most commonly observed forms are inherited congenital sensorineural, acquired later-onset sensorineural (ototoxicity, presbycusis) and acquired later-onset conductive (chronic otitis externa/media). In most dog and cat breeds inherited congenital sensorineural deafness results from perinatal degeneration of the stria vascularis, the vascular bed of the outer wall of the cochlear duct, which leads to hair cell degeneration. The strial degeneration appears to result from the absence of melanocytes, but their function in this structure is unknown. Ototoxicity may result from any of a large number of drugs and chemicals that directly or indirectly destroy cochlear hair cells. The effects are dose-dependent and in rare cases reversible. The most commonly recognized ototoxic drugs are the aminoglycoside antibiotics. Presbycusis, the ageing-related progressive hearing loss unattributable to other causes, is sensorineural but may also include mechanical changes in the tympanum and ossicles. Hearing aids may be accepted by some dogs as long as some residual function remains. Breeds reported to have been affected by congenital sensorineural deafness are listed and those with the highest prevalence are noted. Methods for diagnosis of deafness are described.

Deafness prevalence and pigmentation and gender associations in dog breeds at risk

Hearing function was tested in dogs from breeds at risk for pigment-associated congenital sensorineural deafness - Dalmatian, English setter (ES), English cocker spaniel (ECS), bull terrier (BT), Australian cattle dog (ACD), whippet, Catahoula leopard dog, and Jack Russell terrier. Deafness prevalence was highest in Dalmatians and lowest in ECS. Phenotype correlation studies were performed in breeds with >100 brainstem auditory evoked responses (BAER) tested subjects. No gender differences were observed. No differences were seen between black- and liver-spotted Dalmatians, among the ES roan colour varieties, among the ECS parti varieties, or among the ACD colour varieties. Blue eyes were positively associated and patches were negatively associated with deafness in the Dalmatian. Blue eyes were also associated with deafness in the ES and ECS. White BT were more likely than coloured BT to be deaf. Having one or more parents ear deaf was positively associated with deafness in Dalmatians, ES, and ECS.

Congenital Deafness and its Recognition

Congenital deafness in dogs and cats is primarily of the hereditary sensorineural form associated with white pigmentation genes, although acquired forms of deafness are possible. Highest prevalence is seen in white cats, especially those with blue eyes, and the Dalmatian, with many other dog breeds affected to some extent. This deafness results from degeneration of the cochlear blood supply at age 3-4 weeks, presumably resulting from suppression of melanocytes by the white (cat) or merle or piebald (dog) genes. Mechanism of inheritance is not understood for most breeds. Such animals should not be bred and may present liabilities for their owners. Objective diagnosis of deafness, especially when unilateral, relies on the brainstem auditory evoked response, an electrodiagnostic test where electrical activity in response to a click stimulus is recorded from the scalp using needle electrodes and a special purpose computer. Client counseling guidelines are presented.

A sample and hold amplifier system for stimulus artifact suppression

A sample and hold amplifier system has been described which is capable of eliminating stimulus artifacts from a variety of biological recordings which would otherwise be impossible to interpret during electrical stimulation. Factors contributing to the prolongation of stimulus artifact are discussed in relation to the design requirements of this system. The application of this artifact suppression circuit to monitoring EEG seizures during electrical stimulation is demonstrated.

Heritability and Segregation Analysis of Deafness in U.S. Dalmatians

Hereditary loss of hearing affects many breeds of the domestic dog, but the Dalmatian has the highest prevalence. Approximately 30% are affected in the United States (U.S.) population. It is widely accepted that a relationship exists between deafness and pigmentation in the dog and also in other animals. While the Dalmatian exemplifies this relationship, the genetic origin and mode of inheritance of deafness in this breed are unknown. The goals of this study were to: (1) estimate the heritability of deafness in an extended kindred of U.S. Dalmatians and (2) determine, through complex segregation analysis, whether there is a major segregating locus that has a large effect on the expression of deafness. A kindred of 266 Dalmatians was assembled, of which 199 had been diagnosed using the brainstem auditory evoked response to determine auditory status. Of these, 74.4% (N = 148) had normal hearing, 18.1% (N = 36) were unilaterally deaf, and 7.5% (N = 15) were bilaterally deaf. A heritability of 0.73 was estimated considering deafness a dichotomous trait and 0.75 considering it as a trichotomous trait. Although deafness in the Dalmatian is clearly heritable, the evidence for the presence of a single major gene affecting the disorder is not persuasive.

Flash and pattern reversal visual evoked potentials in C57BL/6J and B6CBAF1/J mice

Visual system responses (visual evoked potentials) to flash (FVEP) and pattern reversal (PRVEP) stimuli were recorded in mice. Two strains were used: black C57BL/6J mice and agouti B6CBAF1/J mice (first generation offspring of C57BL/6J females and CBA/J males.) Subjects were sedated with ketamine and xylazine. Flash rate (FVEP) and stimulus spatial frequency and pattern reversal rate (PRVEP) were varied to determine optimum stimulus parameters. Normative FVEP and PRVEP data were collected from mice of both strains after determination of optimum parameters. Five positive and four negative alternating peaks were routinely observed in the FVEP, while three positive and three negative alternating peaks were seen with the PRVEP. Varying the flash rate, the pattern reversal rate, and spatial frequency significantly affected nearly all amplitude and latency measures in the responses. Significant differences between strains were seen on some, but not all, latency and amplitude measures when the stimulus parameters were varied.

Chronic alumina temporal lobe seizures in monkeys.

Abstract Chronic temporal lobe seizures were induced in 11 monkeys by bilateral implantation of aluminum hydroxide into the hippocampi. With unilateral temporal lobe implants of alumina little or no epileptic activity was found; however, with bilateral alumina implants clinical seizures similar to human psychomotor attacks were initiated in either of the affected temporal lobes. Spread of alumina through the ventricles and/or tissue in some animals resulted in other seizure types, most of which could be controlled by phenobarbital, without eliminating the temporal lobe seizures. The alumina temporal lobe seizures recurred spontaneously for indefinitely long periods; however, no monkey was studied longer than 14 months. The onset of seizure activity was followed by transient anorexia and adipsia which, with large alumina volumes or other debilitating factors, could progress to fatal status epilepticus. Histology revealed that tissue reactions to the alumina included cell loss, gliosis, and neovascularization, with the most severe reaction occurring adjacent to the alumina mass. Alumina which had leaked into the ventricles in some animals reentered the brain tissue at remote sites through the choroid plexus, resulting in multiple foci.

Antibodies to the neural cell adhesion molecule disrupt functional recovery in injured nerves

Tubes containing specific monoclonal antibodies to the neural cell adhesion molecule (N-CAM) were applied to transected sciatic nerves to attempt to perturb the recovery of muscle function. Physiological recordings were used to estimate the return of function. The decline of implanted antibody over 28 days was estimated and negatively correlated with the degree of functional recovery. No significant immune responses were detected in response to the implanted material. The data implicated N-CAM as a significant component of nerve regeneration.

Prevalence of Deafness in Dogs Heterozygous or Homozygous for the Merle Allele

BACKGROUND Deafness in dogs is frequently associated with the pigment genes piebald and merle. Little is known about the prevalence of deafness in dogs carrying the merle allele. OBJECTIVE To determine the prevalence of deafness in dogs heterozygous and homozygous for the merle allele of the mouse Silver pigment locus homolog (SILV) gene. ANIMALS One hundred and fifty-three privately owned merle dogs of different breeds and both sexes. METHODS Hearing was tested by brainstem auditory-evoked response and classified as bilaterally hearing, unilaterally deaf, or bilaterally deaf. DNA from buccal cells was genotyped as either heterozygous or homozygous for the merle allele. Deafness association tests among merle genotype, eye color, and sex were performed by the chi(2) test. RESULTS Deafness prevalence in merles overall was 4.6% unilaterally deaf and 4.6% bilaterally deaf. There was a significant association between hearing status and heterozygous versus homozygous merle genotype. For single merles (Mm), 2.7% were unilaterally deaf and 0.9% were bilaterally deaf. For double merles (MM), 10% were unilaterally deaf and 15% were bilaterally deaf. There was no significant association with eye color or sex. CONCLUSIONS Deafness prevalence in merle dogs was greater than that in some dog breeds homozygous for the piebald gene, such as the English Cocker Spaniel, but comparable to, or lower than, that in the Dalmatian and white Bull Terrier. Dogs homozygous for the merle allele were significantly more likely to be deaf than heterozygotes.

Brain-stem auditory evoked potentials in the alligator. Effects of temperature and hypoxia ☆

Brain-stem auditory evoked potentials (BAEPs) were recorded from young alligators (Alligator mississippiensis), and the effects of hypothermia, hyperthermia and hypoxia on the wave forms were determined. The wave form shape was similar to the human BAEP, although extra waves were routinely seen. The responses were highly repeatable and varied in a predictable manner as a function of stimulus frequency, polarity, intensity, and body temperature. Rarefaction clicks produced longer wave form latencies than condensation clicks. BAEPs were present over the entire temperature range studied (0-36 degrees C). In contrast, mammalian BAEPs disappear over the temperature range of 20-27 degrees C, and seizures occur at 20-21 degrees C. At temperatures below 20 degrees C, the alligator BAEP peak amplitudes decreased with decreased temperature, but latencies only decreased slightly. At temperatures above 20 degrees C the peak amplitudes increased, and the latencies decreased with temperature. Peak I was largely unaffected by temperature change, while peaks IIIa and V increased 0.015 and 0.018 msec/degree C, respectively, at temperatures above 24 degrees C. Transient brain hypoxia, achieved by inverting the alligator, produced a progressive decrease in BAEP waves to an isoelectric amplitude without greatly altered latencies. The reverse sequence of changes was seen during recovery. Postural effects on blood flow were documented in two alligators with implanted flow probes. Carotid artery blood flow decreased 43% with body inversion, in both anesthetized and unanesthetized alligators, but no sequelae from the hypoxia could be detected. Metabolic differences between mammals and the alligator may account for the alligators resistance to hypothermia, hyperthermia and hypoxia.