Adult-Onset Neuronal Ceroid Lipofuscinosis in a Shikoku Inu.

A two-year-and-eleven-month-old male Shikoku Inu was referred for evaluation of progressive gait abnormality that had begun three months prior. Neurological examination revealed ventral flexion of the neck, a wide-based stance in the hindlimb, wide excursions of the head from side to side, tremor in all four limbs, hypermetria in all four limbs, proprioceptive deficits in all four limbs, reduced patellar reflex in both hindlimbs, and postural vertical nystagmus. Later, behavioral and cognitive dysfunction, ataxia, and visual deficits slowly progressed. Magnetic resonance imaging revealed symmetrical progressive atrophy of the whole brain and cervical spinal cord. Bilateral retinal degeneration was observed, and both flush and flicker electroretinograms were bilaterally non-recordable at the age of five years and eight months, and the dog was euthanized. Histopathologically, faint-to-moderate deposition of light-brown pigments was frequently observed in the cytoplasm of neurons throughout the cerebrum, cerebellum, and nuclei of the brainstem. The pigments were positive for Luxol fast blue, periodic acid-Schiff, and Sudan black B, and exhibited autofluorescence. Electron microscopic examination revealed the accumulation of membranous material deposition in the neuronal cytoplasm. Small foci of pigment-containing macrophages were frequently observed around the capillary vessels. Based on these clinical and pathological findings, the animal was diagnosed with adult-onset neuronal ceroid lipofuscinosis.

Effects in cats of atipamezole, flumazenil and 4-aminopyridine on stress-related neurohormonal and metabolic responses induced by medetomidine, midazolam and ketamine.

This study aimed to investigate the antagonistic effects of a fixed dose of atipamezole (ATI), flumazenil (FLU) and 4-aminopyridine (4AP), both alone and in various combinations, on key stress-related neurohormonal and metabolic changes induced by medetomidine (MED), midazolam (MID) and ketamine (KET) in healthy cats. Seven cats were used consistently in eight investigation groups. Cats were administered a mixture of 0.05 mg/kg MED and 0.5 mg/kg MID followed 10 mins later by 10 mg/kg KET intramuscularly. Twenty minutes after KET injection, the cats were intravenously injected with either a physiological saline solution at 0.1 ml/kg (control) or one of the seven variations of experimental drugs, alone or in combination: ATI, FLU, 4AP, ATI + FLU, FLU + 4AP, ATI + 4AP and ATI + FLU + 4AP. Blood samples were collected 10 times during the 24 h test period. Plasma glucose, insulin, cortisol, epinephrine, norepinephrine and non-esterified fatty acid levels were measured. The administration of MED + MID + KET resulted in hyperglycaemia and decreases in epinephrine, norepinephrine, cortisol and non-esterified fatty acid levels. FLU or 4AP alone or FLU + 4AP did not effectively antagonise the effects induced by MED + MID + KET but enhanced the hyperglycaemia. ATI alone was effective in antagonising these effects. Compared with non-ATI regimens, combinations with ATI were more effective in antagonising the effects induced by MED + MID + KET; however, ATI + FLU + 4AP caused large increases in cortisol, epinephrine and norepinephrine concentrations. ATI, both alone and in combination, is effective in antagonising the neurohormonal and metabolic effects of MED + MID + KET in cats. However, ATI + FLU + 4AP is not suitable because of large stress-related hormonal responses.

Neuronal ceroid-lipofuscinosis in longhaired Chihuahuas: clinical, pathologic, and MRI findings.

Neuronal ceroid-lipofuscinosis (NCL) is a rare group of inherited neurodegenerative lysosomal storage diseases characterized histopathologically by the abnormal accumulation of ceroid- or lipofuscin-like lipopigments in neurons and other cells throughout the body. The present article describes the clinical, pathologic, and magnetic resonance imaging (MRI) findings of the NCL in three longhaired Chihuahuas between 16 mo and 24 mo of age. Clinical signs, including visual defects and behavioral abnormalities, started between 16 mo and 18 mo of age. Cranial MRI findings in all the dogs were characterized by diffuse severe dilation of the cerebral sulci, dilated fissures of diencephalons, midbrain, and cerebellum, and lateral ventricular enlargement, suggesting atrophy of the forebrain. As the most unusual feature, diffuse meningeal thickening was observed over the entire cerebrum, which was strongly enhanced on contrast T1-weighted images. The dogs' conditions progressed until they each died subsequent to continued neurologic deterioration between 23 mo and 24 mo of age. Histopathologically, there was severe to moderate neuronal cell loss with diffuse astrogliosis throughout the brain. The remaining neuronal cells showed intracytoplasmic accumulation of pale to slightly yellow lipopigments mimicking ceroid or lipofuscin. The thickened meninges consisted of the proliferation of connective tissues with abundant collagen fibers and mild infiltration of inflammatory cells suggesting neuroimmune hyperactivity. Although the etiology of this neuroimmune hyperactivity is not currently known, MRI findings such as meningeal thickening may be a useful diagnostic marker of this variant form of canine NCL.

Antagonistic effects of atipamezole, flumazenil and 4-aminopyridine against anaesthesia with medetomidine, midazolam and ketamine combination in cats.

Antagonistic effects of atipamezole (ATI), flumazenil (FLU) and 4-aminopyridine (4AP) alone and in various combinations after administration of medetomidine-midazolam-ketamine (MED-MID-KET) were evaluated in cats. Animals were anaesthetised with MED (50 microg/kg), MID (0.5 mg/kg) and KET (10 mg/kg) given intramuscularly. Twenty minutes later, physiological saline, ATI (200 microg/kg), FLU (0.1 mg/kg), 4AP (0.5 mg/kg), ATI-FLU, FLU-4AP, ATI-4AP or ATI-FLU-4AP was administered intravenously. FLU, 4AP alone, or FLU-4AP did not effectively antagonise the anaesthesia, hypothermia, bradycardia, and bradypnoea induced by MED-MID-KET. ATI alone was effective. ATI-FLU, ATI-4AP and ATI-FLU-4AP combinations produced an immediate and effective recovery from anaesthesia. The combination of ATI-FLU-4AP was the most effective in antagonising the anaesthetic effects, but was associated with tachycardia, tachypnoea, excitement, and muscle tremors. Combinations with ATI are more effective for antagonising anaesthesia, but ATI-FLU-4AP is not suitable.