What is the likely diagnosis and treatment for a 6-year-old cat with a history of two seizures, one 4 months ago and another today, with no other behavioral changes or neurological signs?

Differential Diagnosis and Management of Recurrent Seizures in a 6-Year-Old Cat

In a 6-year-old cat with two isolated seizures separated by 4 months and no interictal neurological signs, the most likely diagnoses are structural brain disease (particularly inflammatory disease or neoplasia) or idiopathic epilepsy, and immediate diagnostic workup with MRI and CSF analysis is essential before initiating antiepileptic therapy.

Age-Related Diagnostic Considerations

• Cats with secondary seizure disorders (structural or metabolic causes) have a mean age of approximately 8 years, while cats with idiopathic epilepsy average 3.5 years at onset 1
• At 6 years old, this cat falls in an intermediate zone where both structural disease and idiopathic epilepsy remain possible, though structural causes become increasingly likely with advancing age 1, 2
• The 4-month interval between seizures suggests a slowly progressive process rather than acute metabolic derangement 2

Primary Differential Diagnoses

Structural Brain Disease (Most Likely)

Inflammatory disease is the most common structural cause of feline seizures, with many cases being non-FIP viral in origin 3:

• Inflammatory CNS disease accounts for the majority of structural seizure causes in cats 3, 4
• Toxoplasmosis, FIP, FeLV, and FIV are actually rare causes despite common perception 3
• Non-FIP viral inflammatory diseases are the predominant etiology but often remain unidentified 3

Neoplasia becomes increasingly important in middle-aged to older cats 4:

• Brain tumors (meningioma, lymphoma, glioma) are common structural causes in cats over 5 years 4
• Meningiomas are the most frequent primary brain tumor in cats and can present with isolated seizures 4

Vascular disease and previous traumatic brain injury 4:

• Ischemic events can create seizure foci that manifest months to years later 4
• Remote head trauma may leave epileptogenic lesions 4

Idiopathic Epilepsy (Less Likely but Possible)

• Idiopathic epilepsy is uncommon in domestic cats relative to dogs, but should be considered if no structural or metabolic cause is identified 3, 4
• The incidence of primary epilepsy in cats is unknown and may be underdiagnosed 3
• Diagnosis requires exclusion of structural and metabolic causes through comprehensive workup 2

Metabolic Causes (Less Likely Given Clinical Presentation)

• Hypoglycemia, hepatic encephalopathy, hypocalcemia, and uremia can cause seizures but typically present with additional systemic signs 5, 4
• The absence of behavioral changes or interictal neurological signs makes active metabolic disease less likely 2

Essential Diagnostic Workup

Immediate Laboratory Evaluation

Complete metabolic screening is mandatory to exclude secondary causes 5, 2:

• Complete blood count, comprehensive metabolic panel (including glucose, calcium, electrolytes, liver and kidney function) 5
• Feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) testing 3
• Toxoplasma gondii serology 3
• Thyroid function testing (hyperthyroidism can lower seizure threshold) 2

Advanced Neuroimaging

MRI with contrast is the gold standard for identifying structural brain lesions in cats with seizures 2:

• MRI is superior to CT for detecting inflammatory lesions, small tumors, and subtle cortical abnormalities 2
• Contrast enhancement helps differentiate inflammatory disease from neoplasia 2
• CT may be considered if MRI is unavailable, but has lower sensitivity for many feline brain pathologies 2

Cerebrospinal Fluid Analysis

CSF analysis is critical for diagnosing inflammatory CNS disease, the most common structural cause 3, 2:

• Perform CSF collection at the time of MRI under the same anesthetic episode 2
• CSF analysis can reveal inflammatory, infectious, or neoplastic processes 2
• Avoid lumbar puncture if increased intracranial pressure is suspected based on imaging 6

Treatment Approach

When to Initiate Antiepileptic Therapy

Antiepileptic drug (AED) therapy should be initiated after two or more seizures, particularly when seizures are severe, occur in clusters, or when there is concern for progressive disease 7, 2:

• Two seizures in 4 months meets criteria for treatment initiation 7
• Delaying treatment risks cluster seizures or status epilepticus, which occur commonly in cats 3

First-Line Antiepileptic Drug

Phenobarbital is the first-line antiepileptic drug for cats with recurrent seizures 1, 7:

• Start phenobarbital at 2-3 mg/kg PO every 12 hours 7
• Approximately 40-50% of cats become seizure-free with phenobarbital monotherapy 7
• An additional 20-30% achieve good-to-moderate control (1-10 seizures per year) 7
• Monitor serum phenobarbital levels and liver enzymes regularly 7

Second-Line and Add-On Therapies

For cats refractory to phenobarbital monotherapy, levetiracetam or zonisamide can be added 1:

• Levetiracetam is increasingly used as add-on therapy in refractory feline seizures 1
• Zonisamide and pregabalin are alternative add-on options 1
• Approximately 30% of cats remain poorly controlled despite combination therapy 7

Critical Pitfalls to Avoid

• Do not assume idiopathic epilepsy without comprehensive diagnostic workup including MRI and CSF analysis 3, 2
• Do not delay treatment after a second seizure, as cats commonly develop severe cluster seizures and status epilepticus 3
• Do not discontinue antiepileptic therapy even after years of seizure freedom, as most cats will experience seizure recurrence 7
• Do not overlook non-convulsive seizures—more than 50% of cats with epilepsy experience mild generalized or partial complex seizures that may be subtle 3
• Do not rely solely on seizure severity to predict outcome, as many cats with severe seizures respond well to treatment 3

Prognosis and Quality of Life

• With appropriate treatment, approximately 70% of cats achieve seizure freedom or good-to-moderate control 7
• Duration and subjective severity of seizures typically decrease with treatment 7
• Most treated cats (approximately 72%) maintain good quality of life 7
• Prognosis depends heavily on identifying and treating the underlying cause 4, 2