RESUMEN
A 4 yr old, intact female cocker spaniel was presented for investigation of acute, progressive lethargy/hypersomnia; vestibular signs; and cataplexy. A narcolepsy-cataplexy episode with associated hypertension and bradycardia was triggered during examination. There was no evidence of arrhythmia on electrocardiography during the episode. Hematology, serum biochemistry, and thoracic and abdominal imaging were unremarkable. MRI of the brain and cerebrospinal fluid analysis were compatible with meningoencephalitis of unknown origin affecting the mesencephalon, pons and rostral medulla oblongata. The dog was started on immunosuppressive treatment with prednisolone and cytosine arabinoside, which was subsequently switched to cyclosporine. Narcolepsy-cataplexy episodes could initially still be triggered by offering food; however, they gradually became shorter and less frequent until they completely subsided along with all other clinical signs after 3 wk. No relapse occurred over a 32 mo follow-up period from the diagnosis. Repeated MRI revealed marked reduction in the lesion size; cerebrospinal fluid analysis revealed no abnormalities. Although very rare, symptomatic narcolepsy/cataplexy can occur in dogs and can be secondary to brainstem encephalitis. Cardiovascular changes can occur in association with narcolepsy/cataplexy and should be considered when dealing with patients presenting with these specific clinical signs.
Asunto(s)
Tronco Encefálico/patología , Cataplejía/veterinaria , Enfermedades de los Perros/patología , Meningoencefalitis/veterinaria , Narcolepsia/veterinaria , Animales , Cataplejía/etiología , Perros , Femenino , Inmunosupresores/uso terapéutico , Meningoencefalitis/complicaciones , Narcolepsia/etiologíaRESUMEN
BACKGROUND: Acquired narcolepsy has rarely been reported in veterinary medicine. OBJECTIVE: To describe the presentation, clinicopathological features, diagnostic imaging findings, and management of dogs with suspected-acquired narcolepsy. ANIMALS: Eight dogs with clinical features consistent with acquired narcolepsy. METHODS: A call for suspected cases of acquired narcolepsy was made online, followed by a retrospective review of detailed medical records of potential cases. Dogs were included if episodes consistent with cataplexy were present during examination by a board-certified veterinary neurologist and diagnostic work-up included magnetic resonance imaging of the brain and analysis of cerebrospinal fluid. RESULTS: Seven French Bulldogs and 1 Chihuahua (age range, 9-66 months) were included. Meningoencephalitis of unknown origin was diagnosed in 2 dogs, extracranial foci of inflammation were identified in 2 dogs (aspiration pneumonia, esophagitis, otitis media), and no abnormalities were found on diagnostic investigations in 4 dogs. Prednisolone was used in the management of all dogs, 6 dogs received imipramine, and 2 received cytosine arabinoside. An initial remission of signs was observed in all dogs, but a subsequent relapse of clinical signs was recorded for 4 dogs, of which 3 responded to adjustment or resumption of treatment. CONCLUSIONS AND CLINICAL IMPORTANCE: The presence of cataplexy episodes should prompt a thorough diagnostic work-up to exclude the presence of intracranial (and extracranial) pathology. The potential for both remission and relapse of signs in suspected acquired cases is important for clinicians and owners to be aware of.
Asunto(s)
Cataplejía , Enfermedades de los Perros , Meningoencefalitis , Narcolepsia , Animales , Cataplejía/veterinaria , Enfermedades de los Perros/diagnóstico por imagen , Enfermedades de los Perros/tratamiento farmacológico , Perros , Meningoencefalitis/diagnóstico , Meningoencefalitis/tratamiento farmacológico , Meningoencefalitis/veterinaria , Narcolepsia/diagnóstico , Narcolepsia/tratamiento farmacológico , Narcolepsia/veterinaria , Prednisolona/uso terapéutico , Estudios RetrospectivosAsunto(s)
Péptidos y Proteínas de Señalización Intracelular/farmacología , Péptidos y Proteínas de Señalización Intracelular/fisiología , Neuropéptidos/farmacología , Neuropéptidos/fisiología , Receptores Acoplados a Proteínas G/fisiología , Receptores de Neuropéptido/fisiología , Sueño REM/efectos de los fármacos , Animales , Cataplejía/genética , Cataplejía/veterinaria , Enfermedades de los Perros/genética , Perros , Humanos , Narcolepsia/genética , Narcolepsia/veterinaria , Receptores de Orexina , Orexinas , Ratas , Receptores Acoplados a Proteínas G/deficiencia , Receptores de Neuropéptido/deficienciaRESUMEN
Familial narcolepsy secondary to breed-specific mutations in the hypocretin receptor 2 gene and sporadic narcolepsy associated with hypocretin ligand deficiencies occur in dogs. In this report, a pituitary mass is described as a unique cause of narcolepsy-cataplexy in a dog. A 6-year-old male neutered Dachshund had presented for acute onset of feeding-induced cataplexy and was found to have a pituitary macrotumor on magnetic resonance imaging (MRI). Cerebral spinal fluid hypocretin-1 levels were normal, indicating that tumor effect on the ventral lateral nucleus of the hypothalamus was not the cause of the dog's narcolepsy-cataplexy. The dog was also negative for the hypocretin receptor 2 gene mutation associated with narcolepsy in Dachshunds, ruling out familial narcolepsy. The Dachshund underwent stereotactic radiotherapy (SRT), which resulted in reduction in the mass and coincident resolution of the cataplectic attacks. Nine months after SRT, the dog developed clinical hyperadrenocorticism, which was successfully managed with trilostane. These findings suggest that disruptions in downstream signaling of hypocretin secondary to an intracranial mass effect might result in narcolepsy-cataplexy in dogs and that brain MRI should be strongly considered in sporadic cases of narcolepsy-cataplexy.
Asunto(s)
Cataplejía/veterinaria , Enfermedades de los Perros/etiología , Narcolepsia/veterinaria , Neoplasias Hipofisarias/veterinaria , Animales , Cataplejía/etiología , Enfermedades de los Perros/radioterapia , Perros , Angiografía por Resonancia Magnética/veterinaria , Masculino , Narcolepsia/etiología , Neoplasias Hipofisarias/complicaciones , Neoplasias Hipofisarias/radioterapiaRESUMEN
Cataplexy in the narcoleptic canine has been shown to increase after local administration of carbachol into the pontine reticular formation. Rapid eye movement sleep has also been shown to increase after local administration of carbachol in the pontine reticular formation, and furthermore, acetylcholine release in the pontine tegmentum was found to increase during rapid eye movement sleep in rats. Therefore, in the present study we have investigated acetylcholine release in the pontine reticular formation during cataplexy in narcoleptic canines. Extracellular acetylcholine levels were measured in the pontine reticular formation of freely moving narcoleptic and control Doberman pinschers using in vivo microdialysis probes. Cataplexy was induced by the Food-Elicited Cataplexy Test and monitored using recordings of electroencephalogram, electrooculogram and electromyogram. Basal levels of acetylcholine in the microdialysis perfusates were approximately 0.5 pmol/10 min in both control and narcoleptic canines. Local perfusion with tetrodotoxin (10(-5) M) or artificial cerebrospinal fluid without Ca2+ produced a decrease, while intravenous injections of physostigmine (0.05 mg/kg) produced an increase in acetylcholine levels, indicating that the levels of acetylcholine levels measured are derived from neuronal release. During cataplexy induced by the Food-Elicited Cataplexy Test, acetylcholine levels increased by approximately 50% after four consecutive tests in narcoleptic canines, but did not change after four consecutive tests in control canines. Motor activity and feeding behavior, similar to that occurring during a Food-Elicited Cataplexy Test, had no effect on acetylcholine levels in the narcoleptic canines.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Acetilcolina/metabolismo , Cataplejía/veterinaria , Enfermedades de los Perros , Narcolepsia/veterinaria , Formación Reticular/fisiopatología , Animales , Cataplejía/fisiopatología , Colina/metabolismo , Perros , Femenino , Masculino , Microdiálisis , Narcolepsia/fisiopatología , Fisostigmina/farmacología , Valores de Referencia , Formación Reticular/efectos de los fármacos , Formación Reticular/fisiología , Tetrodotoxina/farmacologíaRESUMEN
Cataplexy in the narcoleptic canine has been shown to increase after systemic administration of cholinergic agonists. Furthermore, the number of cholinergic receptors in the pontine reticular formation of narcoleptic canines is significantly elevated. In the present study we have investigated the effects of cholinergic drugs administered directly into the pontine reticular formation on cataplexy, as defined by brief episodes of hypotonia induced by emotions, in narcoleptic canines. Carbachol and atropine were perfused through microdialysis probes implanted bilaterally in the pontine reticular formation of freely moving, narcoleptic and control Doberman pinschers. Cataplexy was quantified using the Food-Elicited Cataplexy Test, and analysed using recordings of electroencephalogram, electrooculogram and electromyogram. Cataplexy was characterized by a desynchronized electroencephalogram and a drop in electromyogram and electrooculogram activity. In narcoleptic canines, both unilateral and bilateral carbachol (10(-5) to 10(-3) M) produced a dose-dependent increase in cataplexy, which resulted in complete muscle tone suppression at the highest concentration. In control canines, neither bilateral nor unilateral carbachol (10(-5) to 10(-3) M) produced cataplexy, although bilateral carbachol, did produce muscle atonia at the highest dose (10(-3)). The increase in cataplexy after bilateral carbachol (10(-4) M) was rapidly reversed when the perfusion medium was switched to one containing atropine (10(-4) M). Bilateral atropine (10(-3) to 10(-2) M) alone did not produce any significant effects on cataplexy in narcoleptic canines; however, bilateral atropine (10(-2) M) did reduce the increase in cataplexy produced by systemic administration of physostigmine (0.05 mg/kg, i.v.). These findings demonstrate that cataplexy in narcoleptic canines can be stimulated by applying cholinergic agonists directly into the pontine reticular formation. The ability of atropine to inhibit locally and systemically stimulated cataplexy indicates that the pontine reticular formation is a critical component in cholinergic stimulation of cataplexy. Therefore, it is suggested that the pontine reticular formation plays a significant role in the cholinergic regulation of narcolepsy.
Asunto(s)
Atropina/farmacología , Carbacol/farmacología , Cataplejía/veterinaria , Enfermedades de los Perros , Narcolepsia/veterinaria , Formación Reticular/fisiopatología , Análisis de Varianza , Animales , Atropina/administración & dosificación , Carbacol/administración & dosificación , Cataplejía/tratamiento farmacológico , Cataplejía/fisiopatología , Perros , Electroencefalografía/efectos de los fármacos , Electromiografía/efectos de los fármacos , Electrooculografía/efectos de los fármacos , Femenino , Lóbulo Frontal/efectos de los fármacos , Lóbulo Frontal/fisiología , Lóbulo Frontal/fisiopatología , Lateralidad Funcional , Masculino , Narcolepsia/fisiopatología , Fisostigmina/farmacología , Valores de Referencia , Formación Reticular/efectos de los fármacos , Formación Reticular/fisiología , Técnicas EstereotáxicasRESUMEN
Multisystemic chromatolytic neuronal degeneration, a newly recognized disease of Cairn Terriers, is described in a second affected North American puppy. In this puppy, the early onset of hind limb weakness at 11 weeks and rapid development of signs of diffuse CNS involvement were distinctive. Signs of cerebellar dysfunction were prominent, but bouts of cataplectic collapse in this puppy constituted the most distinguishing clinical feature. Although electroencephalograph (EEG) recordings lacked a true rapid eye movement (REM) pattern during cataplectic episodes, cervical electromyograph (EMG) potentials ceased or diminished, and imipramine injection was associated with arousal. Postmortem studies revealed that chromatolytic degeneration was very widespread, affecting many neuronal populations in the brain and spinal cord as well as neurons in sensory ganglia. Although the pattern of chromatolysis varied among affected perikarya, chromatolysis was consistently related to dispersion and loss of ribosomes. In this puppy, as opposed to six studied previously, thoracolumbar myelomalacia also occurred symmetrically in the dorsal horns and adjoining funicular white matter. The metabolic derangement underlying this chromatolytic neuronal degeneration and myelomalacia remains unknown.
Asunto(s)
Cataplejía/veterinaria , Enfermedades de los Perros/patología , Degeneración Nerviosa , Animales , Encéfalo/patología , Cruzamiento , Cataplejía/patología , Perros , Femenino , Ganglios/patología , Neuronas Motoras/patología , Médula Espinal/patologíaRESUMEN
A 1-year-old female Rottweiler with a history of narcolepsy and cataplexy lost weight and became worse when given cholinergic agents and/or prednisolone over a 12-day period. The dog was then treated with imipramine HCl, and has been almost clinically normal for 2 years.
Asunto(s)
Cataplejía/veterinaria , Enfermedades de los Perros/tratamiento farmacológico , Imipramina/uso terapéutico , Animales , Cataplejía/complicaciones , Cataplejía/tratamiento farmacológico , Perros , Electrocardiografía , Femenino , Narcolepsia/complicaciones , Narcolepsia/tratamiento farmacológico , Narcolepsia/veterinaria , Parasimpaticomiméticos/uso terapéuticoAsunto(s)
Cataplejía/veterinaria , Enfermedades de los Caballos/tratamiento farmacológico , Narcolepsia/veterinaria , Animales , Atropina/uso terapéutico , Cataplejía/diagnóstico , Cataplejía/tratamiento farmacológico , Femenino , Enfermedades de los Caballos/diagnóstico , Caballos , Humanos , Imipramina/uso terapéutico , Narcolepsia/diagnóstico , Narcolepsia/tratamiento farmacológico , Neostigmina/uso terapéutico , Parasimpatolíticos/uso terapéutico , Fisostigmina/análogos & derivadosAsunto(s)
Enfermedades de los Perros , Enfermedades de los Caballos , Narcolepsia/veterinaria , Animales , Cataplejía/diagnóstico , Cataplejía/veterinaria , Enfermedades de los Perros/diagnóstico , Enfermedades de los Perros/genética , Perros , Electroencefalografía/veterinaria , Femenino , Enfermedades de los Caballos/diagnóstico , Caballos , Humanos , Masculino , Narcolepsia/diagnóstico , Narcolepsia/genética , Sueño REM , VigiliaRESUMEN
Cataplexy is the abrupt loss of muscle tone experienced by narcoleptics. It is usually precipitated by strong emotions or athletic activity. It has been hypothesized that cardiovascular variables have a role in the triggering of cataplexy. In the present study, we have utilized the narcoleptic canine model to directly investigate changes in heart rate and blood pressure in relation to cataplectic episodes. We found that heart rate increased 18% on average in the 20 s preceding cataplexy onset and then fell during cataplexy. Thus, from a cardiovascular standpoint, cataplexy can be subdivided into two very different periods, the cataplexy onset period with very high and declining heart rate, and the period greater than or equal to 10 s after onset, with greatly reduced heart rate. Heart rate at cataplexy onset was significantly higher than heart rate in rapid-eye-movement (REM) sleep, non-REM sleep, and quiet waking. Blood pressure did not markedly change before the onset of spontaneous cataplexies but decreased significantly during cataplexy. Although blood pressure increases did not precede spontaneous cataplexies, sudden increases in blood pressure, induced pharmacologically or by obstruction of the descending aorta, triggered cataplexy in the most severely affected subjects. A hypothesized role for cataplexy as a homeostatic reflex, triggered by interactions between blood flow, central chemoreceptors, and atonia control mechanisms in the medial medulla, is discussed.
Asunto(s)
Presión Sanguínea , Cataplejía/fisiopatología , Frecuencia Cardíaca , Narcolepsia/fisiopatología , Sueño/fisiología , Animales , Cataplejía/veterinaria , Enfermedades de los Perros/fisiopatología , Perros , Femenino , Masculino , Narcolepsia/veterinaria , Nitroprusiato/farmacología , Norepinefrina/farmacologíaRESUMEN
This is a review of the more common diseases of the spinal cord and various areas of the brain of horses. The results of a two and one-half year study of spinal cord disease are emphasized. After a description of the lesion the salient clinical signs are described and the features that differentiate them from other similar diseases. In the seminar, films of case and slides of lesions will be shown to document these diseases.
Asunto(s)
Enfermedades de los Caballos/diagnóstico , Enfermedades del Sistema Nervioso/veterinaria , Animales , Ataxia/veterinaria , Encefalopatías/veterinaria , Cataplejía/veterinaria , Cauda Equina , Cerebelo/anomalías , Parálisis Facial/veterinaria , Infecciones por Herpesviridae/veterinaria , Caballos , Humanos , Narcolepsia/veterinaria , Neuritis/veterinaria , Infecciones Protozoarias en Animales , Enfermedades de la Médula Espinal/veterinariaRESUMEN
Pharmacological studies using a canine model of narcolepsy have demonstrated that adrenergic rather than serotonergic or dopaminergic uptake inhibition is the primary mode of action of antidepressants on cataplexy, a pathological manifestation of rapid eye movement (REM) sleep atonia that occurs in narcolepsy. This result is in line with the known involvement of adrenergic systems in the regulation of REM sleep. However, the lack of anticataplectic effects of selective serotonergic compounds was puzzling as serotonergic neurons of the dorsal raphe nuclei are known to decrease activity during the REM sleep in a manner similar to the adrenergic neurons of the locus coeruleus. To further explore the role of serotonergic systems, we tested the effect on canine cataplexy of six 5-HT1A agonists and five 5-HT1A antagonists. Results indicate that 5-HT1A agonists significantly suppress cataplexy in correlation with their in vitro affinities to the canine central 5-HT1A receptors. Anticataplectic effects were, however, accompanied by various behavioral changes, such as flattened body posture, increased panting and agitation. In contrast, the selective 5-HT1A antagonist did not aggravate cataplexy, although a 5-HT1A antagonist was able to block the anticataplectic effect of a 5-HT1A agonist. These results suggest that the anticataplectic effects of 5-HT1A agonists are truly mediated by 5-HT1A receptor stimulation. It is, however, likely that anticataplectic effects occur due to the behavioral side effects rather than the direct involvement of this receptor subtype in the regulation of cataplexy. Further studies are therefore necessary to address the question of whether these 5-HT1A agonists hold promise in the pharmacological treatment of human cataplexy.
Asunto(s)
Cataplejía/veterinaria , Enfermedades de los Perros/fisiopatología , Receptores de Serotonina/efectos de los fármacos , Antagonistas de la Serotonina/farmacología , Agonistas de Receptores de Serotonina/farmacología , Animales , Cataplejía/tratamiento farmacológico , Cataplejía/genética , Cataplejía/fisiopatología , Perros , Ensayo de Unión Radioligante , Receptores de Serotonina/metabolismo , Receptores de Serotonina 5-HT1 , Agonistas de Receptores de Serotonina/metabolismo , Agonistas de Receptores de Serotonina/uso terapéuticoRESUMEN
Narcolepsy associated with localized brain lesions is described in a 10-month-old Argentine Dogo. Neurological examination and MRI study suggested an inflammatory lesion of the left frontal lobe. Postmortem examination revealed diffuse encephalitis in the forebrain and marked necrotic lesions in the ventral pontine area. Immunohistochemistry for distemper virus antigen showed positive staining of the cytoplasm of many neurones of the pons and cerebral cortex. The pathological pattern was suggestive of post-vaccinal distemper encephalitis and the localization of the lesions was consistent with the neurological syndrome shown by the animal. At any event, the possibility of coincidental findings of distemper encephalitis and idiopathic narcolepsy must be accounted for.
Asunto(s)
Cataplejía/veterinaria , Enfermedades Desmielinizantes/veterinaria , Moquillo/complicaciones , Enfermedades de los Perros/patología , Encefalitis Viral/veterinaria , Narcolepsia/veterinaria , Animales , Antígenos Virales/análisis , Encéfalo/patología , Encéfalo/virología , Cataplejía/complicaciones , Cataplejía/patología , Enfermedades Desmielinizantes/complicaciones , Enfermedades Desmielinizantes/patología , Moquillo/patología , Virus del Moquillo Canino/aislamiento & purificación , Virus del Moquillo Canino/patogenicidad , Enfermedades de los Perros/etiología , Perros , Encefalitis Viral/complicaciones , Encefalitis Viral/patología , Resultado Fatal , Femenino , Técnicas para Inmunoenzimas/veterinaria , Narcolepsia/complicaciones , Narcolepsia/patologíaRESUMEN
The responses of apparently healthy newborn foals to neurologic testing differ significantly from those of adult horses. These responses and the diagnostic techniques pertinent to neurologic problems are reviewed as a basis for evaluation of the compromised neonatal foal. The more frequently encountered neurologic diseases are discussed in a problem-oriented format. These clinical problems include behavioral abnormalities, convulsions, changes in consciousness, blindness, ataxia without loss of strength, ataxia with weakness and paralysis, and the floppy foal.