Comparing Dog to Human Temporal Lobe Epilepsy

Temporal lobe epilepsy (TLE) is a specific form of epilepsy that has specific pathology. As you might imagine, the pathology is found in the temporal lobe and consists of given cellular degeneration, loss of neurons and sprouting of mossy fibers (what a great term for a fiber). Clinically, TLE often shows facial automatisms (focal seizures) and is commonly drug resistant. As a result, patients with TLE may under go radiation or surgical intervention to manage their epilepsy. A group from the University of Wisconsin Neurology service recently investigated a cohort of 7 dogs with clinical seizures suggestive of TLE to determine if the same pathology was represented in dogs.

Materials and Methods

Seven dogs with focal facial seizures who were euthanized due to progressive disease were included.

Key neuropathologic findings

·         No significant hilar neuron loss was identified in any dog. Cell counts fell within a relatively narrow range, and no hippocampus showed neuron numbers >2 SD below the group mean.

·         No hippocampal asymmetry was detected in neuronal counts between left and right hippocampi.

·         Mossy fiber sprouting was mild in all dogs (median score ~1.1/5), with no cases showing extensive sprouting typical of TLE.

·         No asymmetry in mossy fiber sprouting was found between hippocampi.

·         Overall, none of the dogs met human neuropathologic criteria for TLE, despite having focal seizure semiology.

What does this mean?

These findings indicate that focal seizures in dogs with idiopathic epilepsy are not necessarily associated with TLE-like hippocampal pathology, contrasting with humans. The mild hippocampal changes observed may reflect seizure-related or age-related alterations rather than a distinct epileptogenic lesion. Importantly, previously reported MRI hippocampal asymmetry in some epileptic dogs may be a consequence of focal seizure activity, not evidence of true TLE. This data does not support pursuit of radiation therapy or surgery in dogs with resistant epilepsy, however there may be specific individual differences that warrant considering these treatments on a case-by-case basis.

I thought this article was worth discussing even though the results were negative. Maybe because the results were negative? We always think we could or should be doing more for some pets who are suffering from refractory seizures – and we should keep trying – but this study did not support similarities between human TLE and canine focal seizures. Therefore, without similar pathology, we cannot pursue similar treatments.

Hope you have survived the January vortex and are beginning to get out and enjoy all that winter has to offer in Wisconsin (or wherever you live!). If you enjoy reading the TidBits, please tell associates, new graduates and your veterinary friends. Thanks for reading. I look forward to seeing you soon. 

Reference: https://avmajournals.avma.org/view/journals/ajvr/aop/ajvr.25.07.0260/ajvr.25.07.0260.xml

What is Temporal Lobe Epilepsy?

Temporal lobe epilepsy (TLE) is a newly emerging term in feline seizure discussions and one worth becoming acquainted with. TLE is not an etiology, but rather a specific seizure phenotype (appearance) caused by epileptic seizures in a specific part of the brain (hippocampus) resulting from multitudes of causes.

What does TLE look like?

Cats with TLE have 6 specific stages or appearances. Not all cats go through all 6 stages, nor are all 6 stages apparent. The stages are:

Stage 1: looking around, sniffing, attention

Stage 2: Immobility and staring (arrest)

Stage 3:Orofacial automatism (lip smacking, facial twitching, swallowing, blinking) hypersalivation, mydraisis

Stage 4: Masticatory movement, facial twitching

Stage 5: Head turning, head nodding

Stage 6: Generalized convulsive tonic-clonic seizure

Most cats are observed in stage 2 or 3, and may progress to stage 4 and 5 but stage 6 is rarely observed.

What causes TLE?

Because TLE is not an etiology, but a description of a seizure syndrome located in one part of the brain, any cause of non-TLE seizures can cause TLE seizures as well. This list could include vascular causes, neoplasia, meningoencephalitis (infectious or non-infectious), or idiopathic.

How is TLE diagnosed?

When orofacial automatisms are observed, TLE should be suspected. To confirm TLE, an MRI with changes in the hippocampus is needed. There may be evidence of the seizure etiology such as neoplasia, or vascular disease as well, but the hippocampus must show specific MRI changes. Histopathology can reveal hippocampal sclerosis or necrosis. Some authors think sclerosis precedes necrosis but this sequence isn’t fully established. I won’t bore you with the detailed differences between sclerosis and necrosis, especially since the difference is detected on necropsy.

Can we treat TLE?

Yes! Treat seizures with antiepileptic drugs (AED) as you would any feline or canine seizure disorder. Any 1 seizure more than every 3 months, or longer than 3 minutes warrants a discussion of starting AEDs. Recently, hippocampectomy (removal of part of the hippocampus) has bene published in a cat as a treatment for TLE. This is a well-established treatment for human TLE (a common form of AED-resistant epilepsy in humans) and it carries an extremely high success rate for seizure elimination. Unfortunately, the procedure in cats needs a bit more work before we start considering it standard treatment. The hippocampus is the memory storehouse therefore loss of the hippocampus can cause difficulty with motivation, spatial memory, and learned behavior. Some researchers have described the effect to be similar to feline cognitive disorder in geriatric cats. Hippocampectomy was extensively performed in the 1960s during the time of rapid, although sometimes perhaps unethical, knowledge acquisition of how the brain works in animals and humans. We must acknowledge this work, even if we might find it ethically repulsive today.

Key Points

·         Temporal lobe epilepsy is a syndrome, resulting in damage to the hippocampus and a classic seizure presentation.

·         Temporal lobe epilepsy can be treated, but may be progressive and unresponsive to treatment once the necrosis stage has been reached. How do we know we reached this stage? No one knows antemortem….stay tuned!

·         Cats should take phenobarbital or levetiracetam. These are currently (2023) the only two drugs with enough literature to support their use and predict a reasonable efficacy. (Sorry my zonisamide-using friends.)