From a clinical perspective, seizures are more frequently associated with hemorrhagic strokes (HS) than ischemic strokes. Rare cases develop into long-term epilepsy [11]. Post-stroke ischemic seizures can often be characterized as either early onset or late onset. There are no fixed criteria, but some authors made this definition based on whether the post-stroke seizure occurs before or after day 7. Early onset seizures are more common with HS, and can result in prolonged hospital stay as well as increased mortality. On the other hand, late onset seizures have higher likelihood of developing into chronic epilepsy [12]. There are multiple hypothesis for the mechanism of post-stroke seizures including cortical fibrosis, lack of inhibitory neurotransmission after stroke, inadequate or suboptimal reinnervation pattern during recovery, or vascular dysgenesis during later healing phases of stroke. Research is underway and an established mechanism is yet to be determined. Understanding the mechanism of post-stroke seizures may impact how long the treatment with Antiepileptic Drugs (AEDs) is required, which is important from a patient management standpoint.

The incidence of seizure as a complication of ischemic stroke is approximately 2–4 % [13]. In the Oxfordshire Community Stroke project, the calculated actuarial risk of seizure after ischemic stroke was 4.2 % at 1 year, and approximately 10 % at 5 years. Stroke accounts for approximately one-third of all newly diagnosed seizures in patients more than 60 years old. The Oxfordshire Community Stroke project includes intracerebral hemorrhage cases. One recent study in young adults estimated the incidence of epilepsy in ischemic stroke patients to be around 15 % and the numbers are even higher in intracerebral hemorrhage [14] ranging in one study to be as high as 31 % [15]. Epidemiological and imaging data show that characteristics associated with higher risk of seizures post-stroke include cortical infarcts, involvement of the temporal lobe, and higher NIHSS scores can put the patient at higher risk of seizures in the post-stroke life [12, 16]. There is no randomized trial data to accurately guide physicians in the use of antiepileptic treatments to prevent post-stroke seizures. Physicians should balance the benefits of treatment with AEDs, considering the fact that seizures in ischemic stroke patients hinder recovery and are associated with increased morbidity and mortality, with the potential negative effects of AEDs in recovery and cognition. A North American multi-center cohort study highlighted this risk by reporting increased resource utilization, and decreased 1 month and 1 year survival in patients with post-stroke seizures. The development of safer AEDs opens the possibility for lowering the risks of treating these patients. In the past, prophylactic AED use with combined HS and ischemic stroke patients was not advised because the side effect profile of drugs like Dilantin was considerably high. With newer, safer drugs like Levetiracetam and Lamotrigine available, physicians and pharmacists feel safer in using them in stroke population. The recent debate regarding prophylactic use of AEDs in stroke patients especially after small trials confirmed increased morbidity, mortality for the patient and sizable resource utilization due to seizure in stroke patients, has resulted on the practice of starting patients with HS on AED as a reflex management plan in some emergency rooms [17, 18]. However, there is no evidence supporting this practice and it is not supported by guidelines. In contrast, ischemic stroke patients are less likely to be placed on AEDs until they have a seizure. Some experts advise long term AED only in patients who have late onset post-stroke seizures, as there is higher risk of recurrent seizures in that subgroup. Overall, decisions regarding AED use should be individualized. Factors to consider in that decision include location and size of the ischemic stroke, type of seizure, other metabolic or infectious findings, baseline functional status, EEG findings, age and gender of the patient, and other similar demographics [12, 19, 20]. For example, a young female with gestation potential and a small ischemic stroke may not be the best candidate for AEDs. Similarly, a patient with mild and simple partial seizures can be treated more conservatively compared to a patient with generalized tonic–clonic seizures. Gabapentin, Lamotrigine, and Levetiracetam are considered safer drugs by most neurologists. The first two have Level A evidence in favor of their use in stroke patients [13, 14].

Ischemic stroke frequently leads to depression [21], with an estimated 20–30 % of patients experiencing depression as a complication of ischemic stroke. Some studies have reported the prevalence as high as 65 % [22]. The prevalence of post-stroke depression (PSD) varies depending on the criteria used for diagnosing depression. Some studies classified any patient started on an antidepressant as being depressed, while others required fulfillment of a stricter Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria, which reflects this wide range of prevalence reports [22]. In any case, neurologists and general practitioners who follow stroke patients in both the inpatient and clinic setting would agree that depression is a common complication that adversely affects the long-term outcome [23]. There is a strong rationale to screen for depression in stroke patients, since untreated PSD can negatively impact survival, compliance with medications and rehabilitation, functional outcome, and quality of life. In order to identify stroke patients with depression early and improve the long-term outcome, dedicated stroke centers typically use a nursing depression screening scoring system. The most commonly utilized is thePHQ-9 depression screening form. Interestingly, PSD can be identified as late as 6 months and can persist up to 2 years after stroke. Hence, screening for depression should continue even in the outpatient and home nursing setting.

Today’s commonly used antidepressants (AD) have improved safety profiles resulting in increased AD utilization. There have been several trials depicting better outcome with timely antidepressant use in stroke patients compared with placebo. Initially, tricyclic antidepressants (TCA) showed benefit in stroke patients from a mood and recovery standpoint, but anticholinergic side effects were the limiting factor in some cases. If tolerated, TCAs can still be a good option, as one study demonstrated that moderate to high dose TCAs are slightly more effective than a Selective Serotonin Reuptake inhibitor (SSRI) [24]. Recent research has paid more attention to SSRIs with most studies showing improvement in depressive symptoms [25]. One placebo controlled randomized trial reported 60–75 % reduction in depression symptoms in PSD patients with Fluoxetine. Paroxetine has more anticholinergic side effects than other SSRIs, and hence, cautious use is advised in the elderly. Fluoxetine for PSD has been tried and tested in multiple RCTs with proven benefit in treating depression and improving long-term outcome. A randomized placebo controlled trial called FLAME (Fluoxetine for motor recovery after acute ischemic stroke) reported that early use of fluoxetine with physiotherapy enhanced motor recovery after 3 months in patients with moderate to severe motor deficits from ischemic stroke [26]. The concept of modulation of spontaneous brain plasticity by pharmaco-therapeutics as the mechanism was endorsed by this study. One study supported the prophylactic use of Duloxetine for depression prevention and improved long-term recovery [27], but has not been replicated. SSRI side effects include dry mouth, insomnia, nausea, somnolence, agitation, cardiac conduction abnormalities, and hyponatremia. Patients with low sodium who are discharged on SSRIs should be advised to recheck a sodium level a few weeks after discharge as a precautionary measure [19, 28].

Pain related symptoms are common in stroke patients and can hinder not only rehabilitation therapy but also the overall lifestyle of patients. Due to the highly variable inclusion criteria used by different studies, the prevalence of pain that includes articular pain, musculoskeletal pain, pain related to muscle spasms, headache, and central post-stroke pain syndrome (CPSP), ranges from 8 to 74 % [29]. Comparatively, CPSP as a diagnosis is a more straightforward stroke complication and its estimated prevalence ranges from 1 to 12 %. One prospective study reported the incidence of post-stroke pain at 6 months as the following: shoulder pain 16 %, other joint pain 12 %, other pain 20 %, headache 13 %, hyperesthesia 8 %, possible CPSP 11 %, with a total of approximately 46 % of the total ischemic stroke patients followed up [30]. Another interesting study showed post-stroke chronic pain complaints among 39 % of the stroke patients, only slightly higher than the 30 % in the control group [31].

Among patients complaining of musculoskeletal pain, shoulder pain is the most commonly reported symptom and mostly occurs on the paralyzed side, but can occur on either side depending on the patient’s ambulatory or postural dynamics. Headache was another complaint, but no particular type has been identified. CPSP typically occurs a few weeks to months after a thalamic stroke; however, any other location can trigger CPSP for reasons not completely understood. Epidemiological studies show remission of the pain symptoms with time, with one study reporting prevalence of 21 % 12 months after stroke [32, 33].

Management of post-stroke pain, like other chronic pain syndromes, can be challenging. Treatment can vary and should be individualized to the patient. The presence of spasticity in the paretic side should be evaluated as it could influence treatment choices. The type of pain (e.g., musculoskeletal vs. hyperesthesia) and severity can influence treatment choices. Hyperesthesia can theoretically be managed with gabapentin and pregabalin, but no major clinical studies have confirmed its efficacy. Topical creams may be considered for benign, mild superficial pain symptoms. For musculoskeletal post-stroke pain, some experts recommend amitriptyline and lamotrigine (class IIB) as mainstay of treatment and mexiletine, fluvoxamine, and gabapentin as second-line choices. Refractory patients require expert consultation in a pain clinic and some may even go for repetitive transcranial magnetic stimulation (rTMS), typically reserved as a treatment for patients refractory to more conservative treatments [34, 35]. CPSP, which can be a refractory and debilitating problem, is managed with nor-adrenergic inhibitors, antiepileptics and GABAergics like lamotrigine, gabapentin, and pregabalin [34, 35]. Recently, pain cognitive therapy is also being tried.

Spasticity after stroke is a well-documented complication interfering with functional recovery of stroke patients. It is often accompanied by stiffness-related muscle pain, which limits the motor activity in patients in addition to weakness. After acute ischemic stroke, there is an acute phase of flaccidity after which the muscle tone reemerges, in some instances, pathologically to more than its pre-stroke level, leading to spasticity. Spasticity after stroke is reported to reach its peak in 1–3 months after stroke. However, as experience has shown, patients can experience spasticity many months after their stroke.

One study reported 19 % of all stroke patients were found to have spasticity 3 months after stroke [36]. Another small study in the UK might have overestimated this prevalence, reporting 23 of their 59 studied stroke patients (39 %) were spastic a year after stroke [37]. However, most studies document the prevalence to be around 20–30 %. One comprehensive study that only included EMG confirmed cases in the results, reported 21 % patients had spasticity 13 months post stroke [38]. In general, upper extremities are more prone to being spastic than lower extremities in stroke patients.

Modified Ashworth Scale (MAS) is one of the many tools utilized to assess the severity and ranges of spasticity in patients with various neurological diseases mostly affecting the upper limbs. Rehabilitation therapists have depended on this tool for years due to its bedside convenience and inter-rater reliability in wrist and elbow flexors [39, 40].

Medications that have been tried for managing spasticity secondary to ischemic stroke include diazepam, dantrolene, baclofen, tizanidine, clonidine, and gabapentin. The first three are the more commonly used oral agents [41–43]. Botulinum toxin is now used widely to counter spasticity and improve functional outcome. One study compared botulinum toxin type A (BoNT A) to Tizanidine with BoNT A inferred to be superior in that randomized trial [44]. Trials for spasticity in lower extremities also showed BoNT A to be effective than placebo [45, 46]. Intrathecal administration of baclofen has been successfully tried in a series of cases [47]. Other effective interventions include physical therapy, occupational therapy, aquatics, splints, and biofeedback. Most of the physicians taking care of post-stroke patients would agree that combination techniques of both pharmacological and non-pharmacological therapies together play an effective role in managing post-stroke spasticity [48]. Table 7.2 summarizes conservative and non-conservative approach to PSS.