**4. Neurological examination, electroencephalography, and imaging findings**

#### **4.1 Neurological examination**

Post-stroke epilepsy is common among the elderly. Nonconvulsive seizures are common in elderly patient with epilepsy, and clinical presentation of elderly patients with epilepsy differs considerably from younger patients; less common and nonspecific auras (e.g. dizziness); less frequent automatisms; prolonged post-ictal confusion; common complaints with altered mental status, confusion, and memory disturbance [114].

These characteristics hinder and delay the diagnosis of epilepsy in the elderly. Co-morbid diseases such as hypertension, dementia, transient ischemic attack (TIA), and cardiac diseases can mislead to attribute these symptoms as one of the manifestations of pre-existing conditions in an elderly patient with new-onset epilepsy [114]. It is necessary and important, for example, to evaluate stroke or TIA immediately for patient with new-onset motor aphasia with brain imaging examinations; however, the symptom can be of aphasic seizures per se or in association with various neurological emergencies, especially if the duration of aphasia is brief, severity of aphasia is fluctuating, or other concomitant neurological findings exist. Clinical presentation of elderly patients with new-onset epilepsy is commonly nonspecific, and thus, EEG should be utilized for the diagnosis of epilepsy in the elderly.

Status epilepticus occurs in 9–19% of patients with post-stroke seizures, while status epilepticus following stroke accounted for 14–27% of all status epilepticus in adults [115]. Tomari et al. reported that 24% of post-stroke seizures with status epilepticus are nonconvulsive status epilepticus [115]. The initiation of treatments for nonconvulsive status epilepticus is commonly delayed compared with convulsive status epilepticus because the diagnosis is often difficult without EEG. The evaluation with EEG is mandatory for patients with nonspecific symptoms such as depressed level of consciousness. Subtle neurological manifestations (e.g. myoclonus, rigidity/spasticity, saccadic eye movement, eye/head turning, abnormal reflexes), their fluctuation, and repetitions of their combination (e.g. myoclonus - > rigidity/spasticity - > paresis - > hyperreflexia, tachypnea - > eyelid twitch - > eye open - > pupil dilation - > eye/head turning) are worthwhile to further evaluation for status epilepticus.

#### **4.2 Electroencephalography**

Epileptiform discharges (spikes and sharp waves) in conventional EEG are highly specific to seizure recurrence but not sensitive enough in adult patients (sensitivity 17.3%, specificity 94.7%) [116]. Therefore, lack of epileptiform discharges does not simply exclude the possibility of epileptic seizures. Other nonspecific findings represent both neuronal damage and epileptic activities; amplitude decrease of background activities (e.g. posterior dominant rhythm, fast waves, sleep spindles) and presence of focal slow activities should be serially evaluated.

Recently, long-term, continuous EEG monitoring with video record is increasingly utilized in intensive care unit for early diagnosis of nonconvulsive status epilepticus. Besides conventional EEG seizure patterns (i.e. rhythmic activities with evolution in frequency and amplitude), lateralized periodic discharges, evolving/ fluctuating activities, and abnormal rhythmic fast activities superimposed to rhythmic/periodic activities should be evaluated [117–119]. The Salzburg EEG criteria for diagnosis of nonconvulsive status epilepticus include improvement of EEG after intravenous antiepileptic drugs [120].

#### **4.3 Brain imaging**

Brain computer tomography is a well-established measure to evaluate intracranial hemorrhage, edema, and mass lesions, and has been utilized for deciding the indication of thrombolytic therapy in acute ischemic stroke.

Initial use of brain magnetic resonance imaging is useful not only to detect cerebrovascular disorders and other neurological conditions but also to evaluate seizure foci and spread of seizures via neural network. Hyperintensity of diffusionweighted imaging especially in the cortex and hyperperfusion of arterial spin labeling can help early diagnosis of nonconvulsive status epilepticus [118, 119, 121, 122].

### **5. Treatment strategy: adults in general, and in elderly**

#### **5.1 Prevention of post-stroke seizures and epilepsy**

The prevalence of post-stroke early seizure is high; 4.8% for ischemic stroke and 7.9% for hemorrhagic stroke [5]. Current clinical guidelines recommend against the routine use of prophylactic antiepileptic drugs for spontaneous intracerebral hemorrhage [64], because primary prevention of seizures with antiepileptic drugs does not improve neurological function during follow up (up to 90 days) [65]. For SAH, guidelines state that a short course (3 to 7 days) of prophylaxis with antiepileptic drugs may be started in the immediate post-bleeding period, although this prophylaxis has a low level of evidence [70]. PHT, which can cause worse cognitive

#### *Cerebrovascular Disease; A Leading Cause of Epilepsy DOI: http://dx.doi.org/10.5772/intechopen.95119*

outcomes, vasospasm, and infarctions, should be avoided to use for prophylaxis after SAH, and LEV is increasingly being used [70].

The prevalence of post-stroke late seizure is 3.8% for ischemic stroke and 2.6% for hemorrhagic stroke [5]. As the risk of recurrence after a first unprovoked late seizure can be as high as 71.5% over the next 10 years, the occurrence of a single late post-stroke seizure is consistent with a diagnosis of epilepsy. The risk factors for seizures after ischemic stroke were cortical involvement of infarction and stroke disability. For hemorrhagic stroke, the risk factor of seizures was cortical location. The risk factors in general for post-stroke early seizures during the first 48 hours include advanced age, confusional syndrome, hemorrhagic stroke, large lesions, involvement of parietal and temporal lobes, and occurrence of neurologic and medical complications [6].

None of the currently available antiepileptic medication has been shown to prevent PSE [123–125]. Immediate initiation of continuous antiepileptic medication treatment of the first early seizure after cerebral infarctions decreased the risk of recurrent seizure during the first 2 years but has no influence on the development of recurrent seizures after discontinuing antiepileptic medication in 2 years [124].

As mentioned in Chapter 4, anti-inflammatory therapy is the most expected strategy in order to prevent epileptogenesis. Statins, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, which are approved for cholesterol reduction, may also be beneficial in the treatment of inflammatory diseases. In animal experiment, atorvastatin reverses paralysis in central nervous system autoimmune disease via suppressing secretion of type 1 helper T cell (Th1) cytokines (IL-2, IL-12, interferon-Γ, and TNF-α) and promoting secretion of Th2 cytokines (IL-4, IL-5 and IL-10) and transform of growth factor-β, in Th1-mediated central nervous system demyelinating disease model of multiple sclerosis [126]. In patients with epilepsy, statin use, especially in the acute phase of ischemic stroke, may reduce the risk of post-stroke early-onset seizures [127]. Adequate statin treatment after ischemic stroke may lower the risk of PSE [128].

In the future, periodic measurement of inflammatory biomarker in the stroke patients having the risk factors as mentioned above and evaluation of the effect of anti-inflammatory agents such as statin to epileptogenicity are warranted.

#### **5.2 Treatment of post-stroke seizures and epilepsy**

The decision to initiate antiepileptic medication treatment after a first unprovoked seizure should be individualized and based on age, preference of a patient, and clinical, legal, and socio-cultural factors [129]. Upon commencement of treatment with antiepileptic medication, monotherapy is recommended, among various kinds of antiepileptic medication available. For patients with PSE especially with cerebral infarction, possible adverse event of lipid abnormalities should be avoided to prevent recurrent stroke. High tolerability, which is associated with minimum side effects such as sleepiness or dizziness, is important in elderly patients in terms of safety against falling as well as adherence improvement. In addition, drug interaction is a matter of concern in patients undergoing polypharmacy.

Patients who are treated with enzyme-inducing antiepileptic drugs such as carbamazepine (CBZ), PHT, and phenobarbital (PB) show higher levels of total cholesterol, triglycerides and LDL-cholesterol, although the effects of valproate (VPA) on lipid profiles remain unclear [130]. On the other hand, patients who are treated with enzyme-inhibiting antiepileptic drugs and non-enzyme-inducing antiepileptic drugs are not significantly affected their lipid profile, whereas several reports showed LEV could be associated with higher LDL-cholesterol levels [130]. Due to the side effects of antiepileptic drugs, treatment with non-enzyme-inducing antiepileptic drugs such as lamotrigine (LTG) and LEV is a reasonable treatment strategy in terms of lipid control [130]. In post-stroke seizures and epilepsy, LEV and LTG show higher tolerability than controlled-release CBZ [131].

Weight gain and obesity are associated with hypertension and atherosclerosis. It is well known that VPA, CBZ, PHT, gabapentin, vigabatrin, and pregabalin are associated with weight gain [132–134] while LTG and LEV are not [135, 136], and felbamate, topiramate (TPM), and zonisamide cause weight loss [137, 138].

Carotid-artery intima media thickness (CA-IMT) is an early marker of cerebral atherosclerosis [139]. The old-generation antiepileptic drugs such as CBZ, PHT and VPA are associated with significant increase of CA-IMT in adult patients with epilepsy [139, 140]. On the other hand, the new-generation antiepileptic drugs such as LTG and oxcarbazepine (OXC) have no effects on CA-IMT in adults and children [140, 141].

Hyperhomocysteinemia is an independent risk factor for stroke [142]. OXC, TPM, CBZ, and PB are associated with higher plasma total homocysteine level; adult epilepsy patients treated with LTG and LEV as monotherapy had normal total homocysteine level [143].

Currently, patients with PSE are rarely underwent pre-surgical evaluation even though their seizures are intractable. Good seizure outcome is reported in young generation under 50 years old whose epilepsy onset is at age 20 years or younger, who underwent tailored hemispherectomy based on the findings of stereoelectroencephalography recordings [144]. Approximately 3% of patients with cerebral dural arteriovenous fistula experience seizures [45]. Although status epilepticus is not common among patients with cerebral dural arteriovenous fistula, there is a case report that endovascular intervention improved the seizure control of patients with cerebral dural arteriovenous fistula who present with status epilepticus [145].
