Structural epilepsy is caused by a known and identifiable structural forebrain disorder such as vascular, inflammatory/infectious, traumatic, anomalous/developmental, neoplastic and degenerative diseases. Reported prevalence of structural epilepsy in dogs and cats varies among studies ranging from 25–38% in dogs and 34–87% in cats (Quesnel et al., 1997; Bateman and Parent, 1999; Platt and Haag, 2002; Pákozdy et al., 2008; Schriefl et al., 2008; Zimmermann et al., 2009; Steinmetz et al., 2013). Dogs and cats with structural epilepsy usually present with neurological signs (other than seizures) interictally. However, focal lesions in particular areas of the brain (‘clinically silent regions’), such as olfactory bulb, frontal, and pyriform lobes can result in seizure activity without any other neurological signs. In addition, seizures may be the first clinical sign or the only abnormality the pet owner recognizes, at least initially. The signalment, history, disease onset and course and neuroanatomic localization can help to formulate the most appropriate differential diagnosis list. Diagnostic investigations (see Chapter 10) are aimed at identifying the underlying aetiology of the seizures and, if present, of the other neurological signs. Treatment is aimed at the underlying aetiology of the structural brain disease and seizure control with antiepileptic medications (AEMs). Commonly used first-line AEMs are phenobarbital (PB) and potassium bromide (KBr) (see Chapters 12, 13 and 14). Loading or combination with other AEMs with shorter half-lives (such as levetiracetam or zonisamide, see Chapters 15 and 16) may be required to obtain timely clinical efficacy. New generation AEMs may also be used as first-line monotherapy when PB- or Br-related excessive sedation is a concern (e.g. dogs with brain tumours). The choice and dose of the most appropriate AEM is influenced not only by the underlying disease but also by its possible systemic manifestations or concurrent disorders (e.g. PB is contraindicated in animals with hepatic dysfunction; dose reduction of renally excreted AEMs is necessary in animals with impaired renal function). In addition, interactions between AEMs and treatment of the underlying cause of structural epilepsy have to be considered (e.g. in dogs, PB can alter the pharmacokinetics and as a consequence may decrease therapeutic effect of corticosteroids, cyclosporine, metronidazole and other medications) (see Chapter 13). Animals with structural epilepsy may present with cluster seizures or status epilepticus (Bateman and Parent, 1999; Zimmermann et al., 2009). Detailed information on pathophysiology and management of cluster seizures and status epilepticus are presented in Chapter 23 and 24, respectively.
Disease groups resulting in structural epilepsy are presented in order according to the acronym VITAMIN D.
Vascular
Cerebrovascular accidents (ischaemic, haemorrhagic)
Cerebrovascular accidents (CVAs) result from cerebrovascular disease which involves any pathological process of the blood vessels supplying the brain (Wessmann et al., 2009). CVA, also termed stroke, is characterized by non-progressive (or rapidly progressive) intracranial neurological signs with peracute (6 h) to acute (7–24 h) onset and duration of at least 24 h (Victor and Ropper, 2001). When the neurological signs last less than 24 h, the event is referred to as a transient ischaemic attack (TIA) (Victor and Ropper, 2001). TIAs may precede a CVA.
CVAs can be broadly classified as:
• Ischaemic (resulting from occlusion of a cerebral blood vessel by a thrombus or embolism, causing ischaemic necrosis or infarction); and
• Haemorrhagic (resulting from rupture of an intracranial blood vessel wall, causing haemorrhage into or around the brain) (Wessmann et al., 2009; Garosi, 2010).
Ischaemic CVA can be classified by the territory that the affected blood vessel supplies, the size of the vessel (e.g. territorial infarct with large arterial vessel disease, Fig. 5.1a–e; and lacunar infarct with small perforating arterial vessel disease, Fig. 5.2a–e), the age of the infarct (e.g. recent, organizing), the presence of secondary haemorrhage, the pathogenesis of the stroke (e.g. thrombotic, embolic, haemodynamic) and the suspected underlying aetiology.
Haemorrhagic CVA can be classified according to the anatomical site of the haemorrhage (e.g. epidural, subdural, Fig. 5.3a–d; subarachnoid; intraparenchymal, Fig. 5.4a–f; intraventricular), size of the lesion (e.g. small, large) and the age of the lesion or the suspected underlying aetiology (Wessmann et al., 2009). Several disorders can predispose to ischaemic or haemorrhagic CVA (Box 5.1).
The most commonly reported concurrent medical conditions in dogs with ischaemic CVA include hyperadrenocorticism, chronic renal disease, hypothyroidism and hypertension (Garosi et al., 2005a). Reported concurrent medical conditions in dogs with haemorrhagic CVA include Angiostrongylus vasorum infection, primary or secondary brain tumours, hypertension, hyperadrenocorticism, chronic renal disease and hypothyroidism (Lowrie et al., 2012). A concurrent medical condition has been identified in approximately 50% and 44% of dogs with ischaemic and haemorrhagic strokes, respectively (Garosi et al., 2005a; Lowrie et al., 2012).
Reports of ischaemic or haemorrhagic strokes in cats are limited (Cherubini et al., 2007; Altay et al., 2011). Reported concurrent medical conditions include hyperthyroidism, hypertrophic cardiomyopathy, hepatic and renal disease (Altay et al., 2011). The term feline ischemic encephalopathy has been used to describe cases of peracute onset of neurological signs (including seizures) consistent with a unilateral (focal) forebrain lesion caused by ischaemia associated with Cuterebra larval migration through the cerebrum. It has been suggested that the migrating parasite or the host response leads to vasospasm in the cerebral vasculature, typically the middle cerebral artery, resulting in focal cerebral ischaemia (Glass et al., 1998; Williams et al., 1998).
Clinical signs
Neurological signs in animals with CVA have typically a peracute (6 h) to acute (7–24 h) onset and are nonprogressive or rapidly progressive and subsequently regressive in their evolution. Progression of neurological signs for 24 to 72 h can occur due to worsening cerebral oedema and haemorrhage. Once the neurological signs plateau, they gradually improve in most cases but CVA can be fatal. In animals with ischaemic CVA neurological signs commonly refer to a focal and unilateral intracranial anatomic neuro-localization (Garosi, 2010). In animals with haemorrhagic strokes, neurological signs may refer to more than one intracranial neuroanatomic localization (e.g. forebrain, brainstem or cerebellum) as the haemorrhage usually involves the territory of more than one artery and intracranial pressure (ICP) may be increased. In animals with CVA affecting the forebrain, seizures can occur immediately or several weeks later and are often recurrent (see section on poststroke seizures and epilepsy) (Garosi et al., 2005a; Lowrie et al., 2012). Ocular fundic examination should be performed in all animals with suspected CVA as it may reveal tortuous retinal vessels (suggestive of systemic hypertension) haemorrhage (suggestive of coagulopathy or systemic hypertension) or papilledema (suggestive of increased ICP) (Garosi, 2010).
