Epilepsy is more than a simple seizure disorder: Parallels between human and canine cognitive and behavioural comorbidities.

Psychiatric and cognitive comorbidities have been known to play a major role in human epilepsy for a long time. People with epilepsy (PWE) frequently express signs of varying psychiatric and cognitive disorders affecting their quality and quantity of life (QoL/QaoL). Over the last few years, research on behavioural comorbidities and their effect on the underlying disease have been performed in canine epilepsy. The following article reviews manifestations of comorbidities in canine epilepsy with an emphasis on patterns of clinical signs and their effects on QoL and QaoL. Cognitive and behavioural alterations in epileptic dogs are mainly represented by fear-/anxiety related behaviour and cognitive impairment (CI). Reduced trainability and altered reactions to daily situations are common results of comorbid changes posing obstacles in everyday life of owners and their dog. In addition, clinical signs similar to attention deficit hyperactivity disorder (ADHD) in humans have been reported. Canine attention-deficit-hyperactivity-disorder-like (c-ADHD-like) behaviour should, however, be evaluated critically, as there are no official criteria for diagnosis of ADHD or ADHD-like behaviour in dogs, and some of the reported signs of c-ADHD-like behaviour could be confused with anxiety-associated behaviour. Many intrinsic and extrinsic factors could potentially influence the development of behavioural and cognitive comorbidities in canine epilepsy. In particular, seizure frequency/severity, signalment and factors concerning disease management, such as pharmacotherapy and nutrition, are closely linked with the presence of the aforementioned comorbid disorders. Further studies of behavioural alterations in epileptic dogs are needed to comprehend the complexity of clinical signs and their multifactorial origin.

Epilepsy is more than a simple seizure disorder: Causal relationships between epilepsy and its comorbidities.

This review draws connections between the pathogenesis of canine epilepsy and its most commonly recognised comorbidities: cognitive impairment (CI), attention deficit hyperactivity disorder (ADHD)-like behaviour, fear and anxiety. Uni/bidirectional causalities and the possibility of a common aetiology triggering both epilepsy and the associated diseases are considered. Research on this topic is sparse in dogs, so information has been gathered and assessed from human and laboratory animal studies. Anatomical structures, functional connections, disrupted neurotransmission and neuroinflammatory processes collectively serve as a common foundation for epilepsy and its comorbidities. Specific anatomical structures, especially parts of the limbic system, such as the amygdala and the hippocampus, are involved in generating seizures, as well as cognitive- and behavioural disorders. Furthermore, disturbances in inhibitory and excitatory neurotransmission influence neuronal excitability and networks, leading to underlying brain dysfunction. Functional magnetic resonance imaging (fMRI), interictal epileptiform discharges (IEDs), and electroencephalography (EEG) have demonstrated functional brain connections that are related to the emergence of both epilepsy and its various comorbidities. Neuroinflammatory processes can either cause or be a consequence of seizures, and inflammatory mediators, oxidative stress and mitochondrial dysfunction, can equally evoke mood disorders. The extensive relationships contributing to the development and progression of seizures and comorbid cognitive and behavioural conditions illustrate the complexity of the disease that is epilepsy.