2013). Stroke severity is a major risk factor for the developement of PSS and PSE (Arntz et al., 2013; Conrad et al., 2013; Graham et al., 2013; Jungehulsing et al., 2013).
Data on incidence of PSS and PSE in veterinary medicine are limited. In one study including 33 dogs with brain infarction, two (6%) dogs with forebrain ischaemic infarcts developed recurrent generalized seizures at 10 and 31 weeks after the diagnosis of brain infarction (Garosi et al., 2005a). In another study including 27 dogs with a clinical diagnosis of cerebral ischaemic stoke (Gredal et al., 2013), seizures were reported as part of the acute symptomatology in 15 dogs (56%). Seven of these 15 dogs developed PSE. PSE has also been reported in four of five dogs (Paul et al., 2010), 1 of 16 dogs (Gonçalves et al., 2011) with ischaemic or haemorrhagic strokes affecting the prosencephalon. In addition, recurrent seizures have been reported in 20% (15/75) of dogs with an MRI diagnosis of intracranial haemorrhage (Lowrie et al., 2012).
PSE develops more often in people with initial late PSS than in those with initial early PSS. This may be due to different pathophysiology of early and late PSS. Early PSS may be due to acute cellular biochemical disturbances either in the brain or systemically, such as altered electrolyte and acid–base balance, brain oedema, and release of excitatory neurotransmitters secondary to cerebral hypoxia or metabolic changes, whereas late PSS and PSE may result from gliotic scarring causing persistent changes in the cell networks (Slapo et al., 2006; Menon and Shorvon, 2009).
Acute ischaemia has been shown to lead to increased extracellular concentrations of glutamate and reduced GABA-ergic function, and also to functional or structural impairment of GABA-ergic interneurons. The ischaemic penumbra of a stroke (Fig. 5.5) can contain electrically irritable tissue that provides a focus for seizure activity. The area has been shown to exhibit enhanced release of excitotoxic glutamate, ionic imbalances, breakdown of membrane phospholipids and release of free fatty acids. Epileptogenesis may result from selective neuronal cell death and apoptosis, changes in cellular membrane properties, mitochondrial changes, receptor changes (e.g. loss of GABA-ergic receptors), deafferentation and collateral sprouting (both at the site of ischaemia as well as in remote areas) and inflammatory changes. Experimental data also suggest that epileptogenesis is enhanced by hyperglycaemia at the time of ischaemia (Menon and Shorvon, 2009). Further studies are needed to clarify the pathophysiology of PSS and PSE. PSS may also occur due to recurrent strokes.
Fig. 5.5. Illustration of the core and penumbra of an ischaemic infarct in the brain. In the core of the ischaemic infarct, hypoperfusion is severe and results in necrosis rapidly. The degree of ischaemia and subsequent cellular damage is less severe and potentially reversible in the penumbra (which is the area surrounding the core). The brain tissue within the penumbra may recover normal cellular function if perfusion is restored promptly or may become permanently damaged if ischaemia persists.
There are no evidence-based guidelines for the treatment of PSS and PSE in people and animals. In general, early PSS and particularly status epilepticus are treated aggressively (see Chapter 24). In people, recurrent early seizures are commonly treated with AEM for 3–6 months only, whereas PSE treatment is prolonged similarly to other causes of structural epilepsy (Menon and Shorvon, 2009). The choice of the AEM is influenced by the presence of concurrent disorders (e.g. renal or hepatic dysfunction), pharmacokinetic interactions with other treatments, tolerability and potential adverse effects. To date, no AEM has been identified to be clearly superior in the treatment of PSS and PSE. In people, levetiracetam is considered both safe and effective against post-stroke seizures, and may have neuroprotective effect in brain ischaemia (Belcastro et al., 2011). The benefits of neuroprotective and prophylactic antiepileptic treatment for PSE require further investigations.
Diagnostic investigations
Imaging studies of the brain such as computed tomography (CT) and magnetic resonance imaging (MRI) are necessary to support the diagnosis of CVA, to differentiate between ischaemic and haemorrhagic CVA, and to determine the location and extent of the lesion. CT is very sensitive at detecting acute haemorrhage which appears hyperdense, but it may not detect acute ischaemia in the brain (Garosi, 2010). Conventional MRI can help detecting both ischaemic and haemorrhagic CVA, however differentiation between CVA and other intracranial diseases may be challenging in some cases (Cervera et al., 2011; Wolff et al., 2012). Sensitivity and specificity of routine (not including T2* gradient echo sequences and diffusion weighted images) high-field MRI (with or without provision of clinical data) in overall lesion detection and differentiation of CVAs from neoplastic and inflammatory brain disorders in dogs are 39% and 98%, respectively. Sensitivity and specificity of routine high-field MRI (with knowledge of clinical data) are 33% and 89%, respectively, in the diagnosis of haemorragic CVAs, and 67% and 100%, respectively, in the diagnosis of ischaemic CVAs (Wolff et al., 2012). MRI pulse sequences such as T2* gradient echo (for haemorrhagic CVAs), diffusion and perfusion weighted images (for ischaemic CVAs) and magnetic resonance angiography improve the sensitivity and specificity of the diagnosis of peracute and acute CVA (Garosi, 2010; Cervera et al., 2011).
The MRI features of ischaemic CVA include an intraparenchymal lesion within a vascular territory which:
• is well demarcated from the surrounding normal brain tissue;
• involves primarily the grey matter;
• causes minimal or no mass effect;
• compared to normal grey matter, appears:
• hyperintense on T2-weighted, fluid-attenuated inversion recovery (FLAIR) and diffusion-weighted images (DWIs) (Fig. 5.1a, b, e; 5.2a, b, e);
• hypointense on a synthesized apparent diffusion coefficient (ADC) map derived from two or more diffusion-weighted images;
• iso- to hypointense on T1-weighted images (Fig. 5.1c; 5.2c);
• shows variable contrast-enhancement (usually minimal, peripheral or heterogeneous) 7 to 10 days after onset of neurological signs.
The MRI features of haemorrhagic CVA vary depending on several intrinsic (time from ictus, oxygenation state of haemoglobin, source, size and location of haemorrhage) and extrinsic (pulse sequence and field strength) factors (Table 5.1) (Bradley, 1993; Thomas et al., 1997). Haemorrhage in areas with high ambient oxygen (ventricles; epidural, subdural and subarachnoid space) ‘ages’ more slowly than parenchymal haemorrhage, with a resultant change in time course of haemoglobin degradation. Contrast enhancement due to neovascularization in the surrounding brain tissue can occur 7–14 days after intraparenchymal haemorrhagic CVA and may be minimal, heterogenous or peripheral to ring-like.
Cerebrospinal fluid (CSF) analysis in animals with CVA is either normal, or shows aspecific changes such as mild mononuclear or neutrophilic pleocytosis, elevated
