Introduction

• Download Figure
• Download figure as PowerPoint slide

View Full Size

• Download Figure
• Download figure as PowerPoint slide

• Download Figure
• Download figure as PowerPoint slide

An 18-year-old 3.63-kg neutered male domestic shorthair cat was presented to the Cornell University Hospital for Animals Emergency Service and transferred to the Internal Medicine Service for evaluation because of hyporexia, lethargy, and reported hypersensitivity to “sharp sounds.” Past pertinent history included a possible seizure episode 2 years earlier; this episode was characterized by the owner as circling and trouble breathing for 3 to 4 minutes. The patient had been presented to the Cornell University Hospital for Animals Neurology Service at that time, and neurologic evaluation revealed only mild signs of head and cervical spinal pain. Results of brain MRI and a CSF examination done at that time revealed no clinically relevant findings. The patient was not prescribed any medications, and the signs reportedly did not recur.

On physical examination for the current presentation, the cat was determined to be 5% dehydrated and had a left apical, systolic, grade 3/6 heart murmur. The kidneys were bilaterally small, firm, and irregularly shaped. During the hospital stay, the patient exhibited intermittent, exaggerated, “startle-like” myoclonic jerks in response to various sounds, such as opening the cage door, clicking a pen, and clapping, and occasionally to bright lights, necessitating consultation with the Neurology Service.

Assessment

Diagnostic Test Findings

Hematologic abnormalities consisted of high total protein concentration (9.8 g/dL; reference range, 5.9 to 7.5 g/dL) with mild anemia (Hct, 30% [reference range, 31% to 48%]; hemoglobin, 10.1 g/dL [reference range, 10.9 to 15.7 g/dL]; RBC count, 6.4 X 10⁶ RBCs/μL [reference range, 6.9 to 10.1 X 10⁶ RBCs/μL). Serum biochemical abnormalities consisted of mild hypokalemia (2.6 mEq/L; reference range, 3.8 to 5.5 mEq/L), mild hypochloremia (107 mEq/L; reference range, 111 to 124 mEq/L), low bicarbonate concentration (11 mEq/L; reference range, 14 to 20 mEq/L), high anion gap (35 mEq/L; reference range, 18 to 29 mEq/L), high creatinine (8.0 mg/dL; reference range, 0.8 to 2.1 mg/dL) and BUN (154 mg/dL; reference range, 17 to 35 mg/dL) concentrations, severe hyperphosphatemia (9.7 mg/dL; reference range, 2.6 to 5.5 mg/dL), and mild to moderate hypermagnesemia (2.7 mEq/L; reference range, 1.7 to 2.2 mEq/L). These findings were consistent with advanced renal disease but did not provide a definitive cause for the myoclonic seizures. It is possible that advanced renal disease could predispose to a vascular event and vestibular signs, but this could not be definitively determined without MRI of the brain.

Urinalysis revealed a low specific gravity (1.010; reference range, > 1.030) and proteinuria (100 mg/dL [2+ on a urine dipstick]), indicating that the patient had an abnormal ability to concentrate urine. Bacterial culture of a urine sample did not yield any growth. Total thyroxine concentration was 2.18 μg/dL (reference range, 2 to 5 μg/dL).

Results of echocardiography were indicative of hypertrophic obstructive cardiomyopathy. Radiography revealed moderate, diffuse gastroenteropathy with nonobstructive gastric foreign material. In comparison with thoracic radiographs obtained 2 years earlier, there was progressive, severe, bilateral elbow osteoarthrosis, unchanged, healed fractures of the 11th through 13th ribs, and mildly progressive, multifocal thoracic spondylosis deformans. There was no evidence of metastasis in the lungs. Abdominal ultrasonography showed bilateral, chronic renal degeneration with mild to severe renal pelvic dilation. There was moderate segmented right hydroureter and minimal left ureteral dilation.

An MRI and CSF analysis were not pursued because the patient was deemed a poor candidate for general anesthesia owing to advanced renal disease and hypertrophic obstructive cardiomyopathy.

Treatment

Supportive treatment for advanced renal disease and hydroureter was instituted, which included eventual placement of a subcutaneous ureteral bypass device. The patient was also treated with levetiracetam (30 mg/kg, PO or IV, q 8 h) while in the hospital because of the suspected myoclonic seizures, and the “startle” episodes completely resolved with administration of this medication. When levetiracetam was discontinued briefly during the patient's hospitalization, myoclonic seizures immediately returned, but resolved again following reinitiation of levetiracetam. Given the patient's characteristic myoclonic jerks in response to sound that resolved with levetiracetam, feline audiogenic reflex seizures (FARS) were suspected. This was further supported by the return of the sound-induced myoclonic jerks when levetiracetam was discontinued.

Comments

The condition known as FARS is typically nonprogressive and characterized by myoclonic seizures that are triggered by loud, sudden sounds; most frequently, affected cats are > 15 years of age.¹ Myoclonic seizures are sudden, brief contractions that may be generalized or confined to individual muscle groups.¹ Although FARS syndrome is typically considered nonprogressive, repetitive sound stimulation can result in seizure progression from myoclonic seizures to generalized tonic-clonic seizures.¹ Generalized tonic-clonic seizures are characterized by a loss of consciousness with a sustained contraction of all muscles, known as the tonic phase, and paddling and rhythmic jerking of the animal's limbs, known as the clonic phase. Generalized tonic-clonic seizures can range from seconds to minutes and are often coupled with autonomic signs such as salivation, urination, or defecation. This is followed by a postictal period that may manifest as disorientation, restlessness, ataxia, or blindness. This period can range from a few minutes to a few days.²

The intensity of FARS can increase on the basis of the intensity of the sound that induces them, meaning that higher amplitudes of sound may lead to more severe seizures, regardless of seizure type.¹ Triggers include sounds such as those generated from crinkling tin foil, dropping metallic objects, or clicking a computer mouse.¹ Approximately a third of cats with FARS have concurrent diseases, which is most likely attributable to the geriatric age of onset rather than a causal relationship.¹ Notably, the cat described in the present report had advanced kidney disease as well as hypertrophic obstructive cardiomyopathy. There appears to be no sex bias for FARS; however, there may be a breed predisposition, in that 31% of affected cats reportedly are Birman.¹ Importantly, there are no expected abnormal findings on advanced imaging of the brain in cats with FARS. In the 2016 study by Lowrie et al,¹ 32 cats underwent MRI, and 2 cats underwent CT, and results in all cats were unremarkable. A CSF analysis was performed in 18 cats, and the results were also unremarkable, making this a disease of exclusion on the basis of clinical signs, a lack of findings with advanced imaging, and alleviation with levetiracetam.

The study of sound-induced seizures in animals has shown that the caudal colliculus, where auditory reflexes are relayed, is critical for the initiation of audiogenic seizures.³ A seizure is described as an abnormal electrical discharge in the brain, and when referring to audiogenic seizures, this abnormal discharge moves from the caudal colliculus to other brainstem nuclei.³ Repetitive audible noises allow these brainstem and midbrain electrical stimulations to manifest as limbic stimulations, where forebrain manifestations occur, resulting in epileptic formation and resultant seizures.³

A seizure medication is deemed effective when it reduces seizure frequency by ≥ 50%, and a study⁴ of the treatment of FARS has shown that levetiracetam is more effective than phenobarbital in management of these myoclonic seizures. The 2017 study by Lowrie et al¹ showed that levetiracetam reduced seizure frequency by at least 50%/wk in all cats, whereas a remarkable half of the studied population achieved freedom from myoclonic seizures. In this same study, only 1 of 29 cats had a 50% reduction in myoclonic seizure frequency with the use of phenobarbital, and no cats were free from seizures. Thus, levetiracetam appears to be the treatment of choice, rather than phenobarbital, for geriatric cats with FARS.

In summary, FARS syndrome is typically characterized as a nonprogressive clinical disorder that affects geriatric cats (median age, 15 years) and presents as sound-induced myoclonic seizures. These seizures appear as brief, startle-like episodes in response to typically high-pitched sounds, can progress to generalized tonic-clonic seizures with repeated sound simulation, and are responsive to levetiracetam treatment.