Читать книгу Canine and Feline Epilepsy - Luisa De Risio - Страница 257

Seizures can occur during the active stage of cerebral inflammation, disappear after the inflammation/infection has resolved, they may persist, or they may first manifest in the post-encephalitic period after the inflammation/infection has resolved (see Schwartz-Porsche and Kaiser, 1989; Michael and Solomon, 2012; Chapter 3). The exact risks of developing encephalitis-associated seizures are poorly understood, but appear to relate to the pathogen, the degree of cortical involvement and the cytokine-mediated inflammatory response (Michael, 2012).

Acute post-encephalitic seizures (PES), defined by the International League Against Epilepsy (ILAE) as seizures occurring within 7 days of an acute central nervous system (CNS) infection, have been reported in 2–67% of patients with encephalitis. Late (>7 days) PES usually develop within the first 5 years following encephalitis, but can occur up to 20 years later. The pathogen causing the encephalitis appears important in predicting the likelihood of later developing post-encephalitic epilepsy (PEE). Studies from Western industrialized countries show that patients with encephalitis are overall about 16 times more likely than the general population to develop late PES (Michael and Solomon, 2012). Data on incidence and risk factors for encephalitis-associated seizures are unavailable in veterinary medicine.

Several potential pathophysiologic mechanisms can explain the development of seizures in patients with encephalitis. Experimental evidence indicates a significant role for inflammatory and immune mediators in initiation of seizures and epileptogenesis (Friedman and Dingledine, 2011; Kramer et al., 2012). The inflammatory response and in particular inflammatory mediators (including cytokines such as interleukins (IL), chemokines, prostaglandins and complement factors) produced by astrocytes and microglia are increasingly recognized to promote excitatory neurotransmitter release and consequent depolarization. These inflammatory mediators can have both acute and long-term effects on seizure threshold (Vezzani et al., 2011; Michael and Solomon, 2012). Glial cells, as well as neurons, can over-express receptors for inflammatory molecules, including receptors for proinflammatory cytokines (e.g. IL-1β, IL-6 and tumour necrosis factor-α), as well as toll-like receptors. Cytokines or prostaglandins can induce post-translational changes in receptor-coupled or voltage-dependent ion channels leading to increased glutamatergic neurotransmission or reduced GABA-mediated effects. Proinflammatory cytokines also can decrease glutamate reuptake by astrocytes and can increase the release of excitatory gliotransmitters by activated glial cells, possibly also contributing to neuronal network hyperexcitability. Long-term effects of inflammatory mediators involve gene transcription of proinflammatory genes, which may perpetuate inflammation in brain tissue, and play a role in alterations in blood–brain barrier (BBB) permeability properties. A compromised BBB in turn contributes to decrease seizure threshold by inducing ionic imbalance in the extracellular milieu, as well as astrocytes and microglia dysfunctions. In addition, recent data suggest that cytotoxic T-cells and antibody-mediated complement activation may have a role in neural tissue degeneration and subsequently epileptogenesis (Bauer et al., 2012).

In people, there is currently no evidence to support prophylactic anti-epileptic treatment in all patients with encephalitis. Patients with encephalitis should be closely monitored and administed AEMs promptly if seizures occur. PEE should be treated similarly to other types of structural epilepsy. People with PEE are frequently refractory to AEMs and may require combination therapy or neurosurgery to attempt to control seizures (Michael and Solomon, 2012).