Posts Tagged Epilepsy

[WEB SITE] Epileptic Disorders – How to diagnose and treat post-stroke seizures and epilepsy – Educational


Stroke is one of the commonest causes of seizures and epilepsy, mainly among the elderly and adults. This seminar paper aims to provide an updated overview of post-stroke seizures and post-stroke epilepsy (PSE) and offers clinical guidance to anyone involved in the treatment of patients with seizures and stroke. The distinction between acute symptomatic seizures occurring within seven days from stroke (early seizures) and unprovoked seizures occurring afterwards (late seizures) is crucial regarding their different risks of recurrence. A single late post-stroke seizure carries a risk of recurrence as high as 71.5% (95% confidence interval: 59.7-81.9) at ten years and is diagnostic of PSE. Several clinical and stroke characteristics are associated with increased risk of post-stroke seizures and PSE. So far, there is no evidence supporting the administration of antiepileptic drugs as primary prevention, and evidence regarding their use in PSE is scarce.


Neurologists frequently encounter seizures related to stroke. Given that post-stroke epilepsy (PSE) is the most common form of acquired epilepsy, it is quite surprising that it has attracted little academic interest and that, so far, only scarce evidence is available to guide clinical practice. The scenario is, however, changing and both basic science researchers and clinical investigators have started to address highly relevant issues, including pathophysiology, prevalence and incidence, diagnosis, prevention, treatment, and prognosis.

When should PSE be diagnosed? When should treatment start? Which is the most effective treatment? Which antiepileptic drug (AED) should be preferred? Not all seizures occurring after stroke are necessarily stroke-related. So, when should PSE be diagnosed? Only an adequate knowledge and correct diagnosis may spare patients the anxiety, stigma, and side effects of unnecessary treatments.

In recent years, interesting developments in the field of epileptogenesis also suggests that the risk of PSE may be modified through pharmacological intervention. In addition, the association found between PSE and risk of vascular events highlights the importance of secondary stroke prophylaxis.

This seminar paper aims to provide an updated overview of PSE and offers clinical guidance to professionals involved in the treatment of patients with post-stroke seizures.



A distinction between early and late post-stroke seizures is mandatory in the field of seizures and stroke since it underscores different pathophysiological mechanisms. Early post-stroke seizures reflect an acute, and perhaps reversible cerebral injury (i.e. acute symptomatic, provoked) whereas late seizures arise from long-lasting changes in the post-stroke brain (i.e. remote symptomatic, unprovoked). In this article, we will use the terms “early and late post-stroke seizures” throughout. The distinction between early and late seizures is closely linked to the theoretical concept of epileptogenesis -the hereto incompletely characterized process by which the brain acquires an enduring predisposition to seizures. Epileptogenesis does not simply represent a process that starts at stroke onset and manifests with seizures at a later stage, but should be considered within the frame of a threshold model in which individual predisposition, stroke characteristics, and subsequent reactions to the primary injury converge with PSE.

The temporal limit to consider a seizure as a “late-seizure” ranges mostly between one and two weeks after stroke, in analogy with the concept of early and late post-traumatic seizures. A pivotal study in Rochester, Minnesota demonstrated that a seizure within seven days of a stroke carries a ten-year risk of a subsequent unprovoked seizure of 33% (95% confidence interval [CI]: 20.7-49.9), whereas a seizure occurring seven days after a stroke carries a ten-year risk of 71.5% (95% CI: 59.7-81.9) (Hesdorffer et al., 2009). Based on such differences in patient prognosis, seven days is currently the recommended cut-off for considering a post-stroke seizure as early or late (Beghi et al., 2010). According to the most recent diagnostic criteria, epilepsy can be diagnosed after a single seizure and with a recurrence risk >60% within the next ten years (Fisher et al., 2014). As shown by the Rochester study, patients presenting with a single late seizure after a stroke carry such a risk. Therefore, one late unprovoked post-stroke seizure can be diagnosed as PSE.

However, it is important to recognize the pitfalls of the seven-day cut-off in order to distinguish between early and late seizures (see below under: “When and how to clinically diagnose post-stroke epilepsy”). The risk of PSE is substantially higher in patients who have presented with an early post-stroke seizure than in patients who have not had any seizure. The occurrence of early seizures is, indeed, an independent risk factor for PSE and weighs heavily in the SeLECT score. The SeLECT score is a recently developed and validated clinical tool to predict late seizures/epilepsy after ischaemic stroke. In addition to the occurrence of an early seizure, it takes into account the severity of stroke, aetiology of stroke, and cortical and arterial territory involved (Ferlazzo et al., 2016; Galovic et al., 2018). An early seizure, not considered epilepsy, should therefore not convey the message that the patient is at no risk of PSE. Clinical risk models and biomarkers must be incorporated in the future to help identify the mechanisms of PSE and refine the diagnosis of PSE in some patients with early seizures and reassure those at low risk of recurrence.


Much of the pathophysiology underlying seizures after stroke remains elusive. Experimental stroke studies have mapped a number of reactions following brain injury, which are common to other models of acquired epilepsy and include inflammatory response, changes in the expression of proteins involved in neuronal signalling, and remodelling of cytoskeleton, but causal links have not been clearly established. Increased blood-brain barrier permeability could also play a pathogenic role (Pitkänen et al., 2016).

Early post-stroke seizures should be regarded as a reaction of the neuronal cells to the acute cerebrovascular injury. They reflect transient cellular biochemical dysfunctions, including -among others- the increased release of excitatory neurotransmitter glutamate, ionic imbalance, breakdown of membrane phospholipids, and release of free fatty acids with oxidative stress (Tanaka and Ihara, 2017). Homeostatic or systemic disturbances, such as electrolyte imbalance, acid-base disturbances and hyperglycaemia, may also play a role in the development of early post-stroke seizures (Tanaka and Ihara, 2017). Conversely, late post-stroke seizures reflect a structural change of neuronal networks following the cerebrovascular injury to the brain (Trinka and Brigo, 2014). They are usually attributed to epileptogenic gliotic scarring with changes in membrane properties, neuronal deafferentation, selective neuronal loss or collateral sprouting (Tanaka and Ihara, 2017). Late post-stroke seizures after a primary cerebral haemorrhage or secondary haemorrhagic transformation of an ischemic stroke are thought to be the consequence of haemosiderin deposits leading to increased neuronal excitability. During post-stroke epileptogenesis, the brain undergoes molecular and cellular alterations, which increase its excitability and eventually lead to the occurrence of recurrent spontaneous seizures. These progressive neuronal changes include selective neuronal cell death and apoptosis, changes in membrane properties, mitochondrial and receptor changes (e.g. loss of GABAergic receptors), deafferentation, and collateral sprouting (Pitkänen et al., 2016). Disruption of the brain-blood barrier following endothelial damage causes extravasation of albumin which in turns activates astrocytes and microglial cells; this leads to changes in the extracellular milieu with increased glutamate levels, release of inflammatory cytokines, and further increase in brain-blood barrier permeability (Tanaka and Ihara, 2017). Thrombin, a major component of the coagulation cascade, and its protease-activated receptor 1 (PAR1), may further contribute to maladaptive plasticity leading to permanent structural changes in the brain with altered neuronal firing and circuit dysfunctions (Altman et al., 2019). This complex cascade of events directly enhances neuronal excitability and could explain epileptogenesis after a stroke. Alterations in gene expression after a stroke can also play a role in epileptogenesis, as they can be associated with impaired neuroprotection, aberrant synaptic plasticity, upregulation of neuronal excitability, and enhanced gliotic scarring formation (Pitkänen et al., 2016). Of note, these pathophysiological mechanisms interact with each other and eventually lead to structural and functional alterations of neuronal networks, leading to recurrent spontaneous seizures (Tanaka and Ihara, 2017).

Remarkably, the current pathophysiological perspective of acquired epilepsy favours a threshold model, which also involves individual predisposition. For instance, individuals with a first-degree relative suffering with epilepsy are at higher risk of developing PSE (hazard ratio: 1.18; 95% CI: 1.09-1.28) although this was associated with a small effect size (Eriksson et al., 2019). Lesion characteristics may be more important in most cases such as size of the lesion, cortical involvement and presence of intralesional blood products (see below under “Neuroimaging of post-stroke seizures: pitfalls and differential diagnosis”).

Until now, the early treatment of stroke patients with AEDs during the acute phase has not been effective in reducing the risk of developing PSE (Gilad et al., 2011; Sheth et al., 2015). On the other hand, statins appear to be the only medication to decrease the risk of PSE (Etminan et al., 2010), and to a greater extent in patients who present with early seizures and are considered a high-risk group (Guo et al., 2015). However, causality and mechanisms of the effect of statins are not yet well-established.


The rates of early post-stroke seizures and PSE vary across stroke populations. For ischaemic stroke, the prevalence of early seizures is generally 3-6% (Beghi et al., 2011; Labovitz et al., 2001; Guo et al., 2015; Serafini et al., 2015) but can be up to 15% in selected cohorts (Labovitz et al., 2001; Lamy et al., 2003; Bentes et al., 2017). There is no converging evidence about the risk of early seizures in patients treated with reperfusion therapies, either intravenous thrombolysis or endovascular thrombectomy (Belcastro et al., 2020; Brigo et al., 2020a; Feher et al., 2019). The risk of intracerebral haemorrhage is somewhat higher (Qian et al., 2014), with early seizures occurring in approximately 10-16% of patients (Naess et al., 2004; Beghi et al., 2011; Procaccianti et al., 2012). However, the methodology adopted to ascertain and diagnose early post-stroke seizures can greatly affect the results. For instance, a study using video-EEG recording performed in the first 72 hours following an acute anterior circulation ischaemic stroke revealed early seizures in 14.6% and non-convulsive status epilepticus (SE) in 2.6% of patients; of note, almost a quarter (22.7%) of early seizures were exclusively electrographic (Bentes et al., 2017).

Data on PSE prevalence also depend on the study population and methodology used to collect data. Based on nationwide registers in Sweden, the cumulative incidence of PSE was 6.4% following ischaemic stroke and 12.4% following haemorrhagic stroke after a follow-up of almost five years (Zelano et al., 2016); the latter finding has been replicated in a population-based investigation in a Finnish region (Lahti et al., 2017). In a video-EEG study, 15.2% of patients suffering with an anterior ischemic stroke met the diagnostic criteria for epilepsy at 12 months (Bentes et al., 2017).

A diagnosis of PSE (after ischaemic and haemorrhagic stroke) increases the risk of mortality after adjusting for stroke severity (Zelano et al., 2016) and, unsurprisingly, vascular disease is the major cause of death. These findings call for concerted efforts to prioritise and optimize secondary vascular prophylaxis (Hansen et al., 2017), and AEDs that do not interfere with concomitant medications, such as anti-hypertensives and anticoagulants, should be preferentially chosen.

The main risk factors for early post-ischaemic stroke seizures are cortical involvement, severe stroke, haemorrhagic transformation, age younger than 65 years, a large lesion and atrial fibrillation (Feher et al., 2019). The main risk factors for PSE following ischaemic stroke are cortical involvement, haemorrhage, and early seizures (Ferlazzo et al., 2016).


The concept of early and late seizures and PSE is straightforward to apply in clinical practice in most cases. If a patient has a seizure within a week of stroke, it is an early seizure and considered acute symptomatic. Although such a seizure carries a risk of subsequent epilepsy, this risk does not warrant the diagnosis of PSE. In contrast, a seizure occurring more than one week after stroke is considered an unprovoked late seizure. This infers a >60% risk of seizure recurrence and the patient meets the diagnostic criteria for epilepsy.

In some circumstances, the distinction between early and late seizures may not be unequivocal. The clinical situation may have been unstable, and the exact time of the latest cerebral insult may not be clear. As per the definition of epilepsy recommended by the International League Against Epilepsy, the diagnosis requires a risk of seizure recurrence exceeding 60%, however, the exact risk in each case is hard to estimate with precision. If there is doubt whether a seizure has occurred within the acute symptomatic phase, then there is no clear evidence of a >60% recurrence risk. In this scenario, the diagnosis of PSE should not be made. A similar approach can be suggested if there is doubt whether a paroxysmal post-stroke event is actually a seizure. In the presence of uncertainty, it is probably better not to diagnose a late seizure/PSE, but rather adopt a wait-and-watch approach. It is important to emphasize, however, that whether a patient is or is not diagnosed with PSE, the decision to initiate treatment with AEDs will depend on clinical characteristics of individual patients.


In the early phase following an ischaemic or haemorrhagic stroke, electroencephalogram (EEG) is an essential diagnostic tool that aims to detect purely electrographic seizures. It can also detect specific patterns, such as lateralized periodic discharges (LPDs), that are independently associated with early seizures (Mecarelli et al., 2011).

Interestingly, brain single-photon emission computed tomography (SPECT) imaging can reveal focal hypermetabolism with increased cerebral blood flow in association with LPDs in patients with post-stroke seizures; such findings support the view that – at least in some patients – this EEG pattern may correspond to an ictal phenomenon (Ergün et al., 2006; Hughes, 2010).

The lack of a systematic electrophysiological assessment with video-EEG can lead to an underestimation of seizures, particularly in the case of focal unaware or non-convulsive seizures (Belcastro et al., 2014; Bentes et al., 2017; Brigo et al., 2020a, 2020b). Neurologists and health personnel working in stroke units should promptly request an EEG recording for patients with sudden onset of unexplained behavioural changes or impairment of consciousness. A continuous EEG lasting ≥24 hours should be recorded as soon as possible in patients with acute supratentorial brain injury presenting with altered mental status or with clinical paroxysmal events suspected to be seizures. In addition, in comatose patients, patients with periodic discharges, or patients who are pharmacologically sedated, a more prolonged EEG (≥48 hours) may lead to the detection of non-convulsive seizures (Herman et al., 2015). The main indications for continuous EEG in patients with acute stroke, to identify non-convulsive seizures and non-convulsive status epilepticus, are presented in table 1.

EEG recordings may also have implications in the prediction of functional outcome, mortality and post-stroke cognitive decline, with different levels of evidence (Doerrfuss et al., 2020).

Only few studies have, so far, assessed EEG as a predictive tool for post-stroke seizures and epilepsy. Abnormalities on EEG can predict the development of epilepsy in the first year after stroke, independently of clinical and imaging-based infarct severity. A retrospective study of 110 patients with ischaemic stroke-related seizures found LPDs in 5.8% of patients, whereas the 275 stroke patients who did not suffer an early and/or a late seizure did not present with LPDs (De Reuck et al., 2006). Diffuse EEG slowing and frontal intermittent rhythmic delta activities also occurred more frequently among patients with post-stroke seizures compared to controls (21.7% versus 5.1% and 24.6% versus 1.1%, respectively) (De Reuck et al., 2006). A prospective video-EEG study enrolled 151 patients with anterior circulation ischaemic stroke and no previous seizures. Asymmetric background activity and interictal epileptiform activity detected on EEG performed during the first 72 hours after stroke were independent predictors of PSE during the first year following the index event (Bentes et al., 2018).

These findings suggest how EEG recorded in the acute stroke phase may not only detect subclinical seizures, but also may provide useful information to predict the development of PSE. Further studies are warranted to assess whether the inclusion of EEG findings with existing scores (e.g. SeLECT [Galovic et al., 2018]) could improve their predictive accuracy (Doerrfuss et al., 2020).

Most studies available in the literature refer to the use of EEG in the acute phase as a predictor of unprovoked late post-stroke seizures. In patients with PSE, EEG usually shows multifocal or focal slowing, typically with a normal background alpha rhythm (Mecarelli and Vicenzini, 2019). Epileptiform abnormalities can be detected, usually as sharp waves, sometimes with a quasiperiodic pattern of recurrence, particularly in PSE associated with large cortical cerebrovascular lesions (Brigo and Mecarelli, 2019; Mecarelli and Vicenzini, 2019).


Seizures are an expression of sudden depolarization of neurons that transiently disrupts ionic and metabolic homeostasis. There are different proposed pathophysiological mechanisms for early and late seizures, which include critically reduced local blood flow, abnormal release of neurotransmitters, metabolic dysfunction, presence of gliotic scarring and aberrant synaptic connectivity (Pitkänen et al., 2016). Of note, only a minority of stroke patients will develop seizures and there is still scarce understanding of magnetic resonance imaging (MRI) signatures that can identify the patients at higher risk. Some studies have identified the following MRI predictors: watershed infarctions, middle cerebral arterial territory strokes, cortical involvement, haemorrhagic strokes and haemorrhagic transformation of ischaemic stroke (Ferlazzo et al., 2016; Galovic et al., 2018).

Caution is, however, necessary in considering a post-stroke seizure as stroke related. In such cases, neuroimaging is fundamental in providing a differential diagnosis.

In acute settings, cranial computed tomography (CCT) is the gold standard to rapidly image patients presenting with seizures. It also represents the only available neuroimaging tool in patients who cannot undergo MRI. Besides standard CCT, perfusion CT (PCT) can be helpful in differentiating between stroke, stroke mimics and status epilepticus (Strambo et al., 2018). Ongoing seizure activity or SE are characterized by regions of hyperperfusion that usually involve atypical vascular territories, whereas strokes typically correspond to hypoperfused areas in a precise arterial territory (Payabvash et al., 2015). PCT can also be helpful to differentiate postictal versus stroke related focal neurological deficits: the former are characterized by transient iso- to hyperperfusion and the latter by areas of hypoperfusion in a vascular territory (Brigo and Lattanzi, 2020). Notably, PCT must be performed within a strict interval from seizure onset (< three hours) to improve its sensitivity (Payabvash et al., 2015).

MRI remains the most sensitive non-invasive diagnostic tool to image the brain, and conventional MR sequences suffice in most cases of suspected post-stroke seizures. The most common conventional sequences are listed in table 2. Diffusion-weighted imaging (DWI) is an informative sequence and is now routinely used in clinical settings. It is fast (acquisition requires less than a minute) and demonstrates high sensitivity for areas of water restriction, making it a very commonly used sequence to differentiate stroke from stroke mimics. Nonetheless, timing of acquisition is extremely important to avoid pitfalls. Lesions can be falsely positive (those containing a very high water content, also known as “T2 shine-through” artefact) or falsely negatively (MRI scans acquired too late after symptom onset) (Agarwal et al., 2017; Shono et al., 2017). Restricted signal on DWI due to seizure activity is mostly reversible (figure 1), whereas it may last three to four days in stroke, unless cerebral tissue has been reperfused earlier. Other lesions that may present with DWI positive signal include subacute haematomas, hypercellular tumours and abscesses (figure 2). Recently, Koksel et al. proposed the acronym “CRUMPLED” as a helpful way to remember the most important DWI-restricted lesions that are cortically based and have an atypical vascular distribution. The acronym stands for C = Creutzfeldt-Jakob disease; R = reversible cerebral vasoconstriction syndrome; U = urea cycle disorders and uraemia; M = mitochondrial disorders; P = prolonged seizures and posterior reversible encephalopathy syndrome (PRES); L = laminar necrosis (hypoxic-ischaemic encephalopathy) and liver-related (acute hepatic or hyperammonaemic encephalopathy); E=encephalitis (infectious meningoencephalitis) and D = diabetes mellitus (hypoglycaemia) (Koksel et al., 2018) (figure 2).

Intravenous gadolinium-based imaging can be particularly useful to: a) identify areas of disrupted blood-brain barrier; b) provide evidence of reperfusion or presence of collateral flow; and c) identify stroke mimics.

Advanced imaging can provide additional and more accurate information for the differential diagnosis.

Perfusion weighted imaging (PWI) can reliably identify tissue at risk of infarct, defined as an area with a blood flow of less than 50 mL per 100 mL of brain tissue per minute (Jahng et al., 2014). Signal changes in PWI are related to electrographic ictal activity: hyperperfusion is likely to be seen in pre-ictal and ictal phases, whereas hypoperfusion is more common in the post-ictal phase (Takahara et al., 2018). Early seizures are more likely to present as areas of hyperperfusion due to the underlying pathophysiological mechanisms, including metabolic dysfunction and abnormal release of neurotransmitters, whereas late seizures are likely to show a mixed pattern of perfusion as they are more related to gliotic changes and loss of neuronal tissue (Yoo et al., 2017). Hyperperfusion may also precede DWI signal changes as a compensatory mechanism to support the abnormally increased depolarization of neurons (Takahara et al., 2018). Susceptibility weighted imaging (SWI) and gradient-echo (GRE) sequences can be highly informative and detect punctuate microbleeds and areas of iron-laden products in patients with subarachnoid haemorrhage, chronic subdural haematoma, cerebral amyloid angiopathy or superficial siderosis. Extracellular haemosiderin is considered epileptogenic and may cause focal cerebral irritation and initiate seizures, even though the mechanisms are not yet well-established (O’Connor et al., 2014).


Due to the rather low risk of early, acute-symptomatic post-stroke seizures, ranging from 3-6% in cases of cerebral ischaemia to 16% in primary cerebral haemorrhage (Labovitz et al., 2001; Naess et al., 2004; Beghi et al., 2011; Procaccianti et al., 2012; Guo et al., 2015; Serafini et al., 2015), primary prophylaxis with an AED is not recommended. This is also true for those patients who have cerebral haemorrhage involving cortical structures and a risk of early post-stroke seizures of around 35%. If physicians decide to introduce primary AED prophylaxis despite the evidence-based recommendations, an AED that can be titrated very quickly, administered intravenously, and which lacks significant drug-drug interactions should be preferred. One of the most commonly prescribed AEDs that meets these characteristics is levetiracetam (LEV). One randomized controlled trial compared valproate to placebo in 36 patients, both of which were administered directly after intracerebral haemorrhage (Gilad et al., 2011). The groups did not differ with respect to prevention of early post-stroke seizures (defined in that study as occurring within the first 14 days), but the trial was underpowered, and prevention of early seizures was not the primary endpoint.

After the occurrence of one early post-stroke seizure, the risk of developing a second acute symptomatic seizure within the acute phase is only 10-20% (De Herdt et al., 2011; Leung et al., 2017). Due to the low risk of recurrence, guidelines generally do not recommend secondary AED prophylaxis after an early post-stroke seizure (Holtkamp et al., 2017). However, many clinicians prefer to administer an AED to reduce the likelihood of clinical worsening in the acute setting. Conceptually, this approach likely relies on pathophysiological considerations including increased neuronal excitotoxicity, peri-infarct depolarisations, and inflammatory responses in the first hours and days after stroke (Dirnagl et al., 1999), all of which can be risk factors for acute recurrence of epileptic seizures. The criteria used to choose the AED for acute secondary prophylaxis are similar to those for primary prophylaxis.

If patients without or after an early post-stroke seizure have been administered an AED, physicians are encouraged to withdraw it after the acute phase – at best, at discharge from the stroke unit – as the vast majority of these patients will not experience any future seizures (Holtkamp et al., 2017). The risk of a first unprovoked post-stroke seizure within eight years (which would define epilepsy) after cerebral infarct is 8% and 15% after cerebral haemorrhage (Merkler et al., 2018), and the risk of an unprovoked seizure after one early post-stroke seizure with 10 years is 30 to 35% (Hesdorffer et al., 2009; Galovic et al., 2018). Two studies developed scores to estimate the long-term risk of unprovoked seizures after acute cerebrovascular events. The CAVE score indicates a five-year seizure risk of 46.2% in patients after intracerebral haemorrhage based on the following four variables: early post-stroke seizure(s), cortical involvement, bleeding volume of more than 10 mL, and age of less than 65 years (Haapaniemi et al., 2014). The SeLECT score indicates a five-year seizure risk of more than 50% in patients after ischaemic stroke based on the following four or five criteria: early post-stroke seizure(s), severe stroke (NIHSS ≥11), cortical involvement, and large-artery atherosclerosis and/or involvement of the middle cerebral artery territory (Galovic et al., 2018). In these individual risk constellations, long-term secondary AED prophylaxis may be indicated.


AED treatment is advised based on guidelines when PSE is diagnosed (Holtkamp et al., 2017). As always, there may be individual reasons not to start treatment -for instance, in cases with very mild semiology. Regarding the selection of drugs, two underpowered randomized, open-label studies compared controlled-release carbamazepine (CBZ-CR) to lamotrigine (LTG) (Gilad et al., 2007) and LEV (Consoli et al., 2012). The 12-month seizure freedom rates were 44% and 85% for CBZ-CR and 72% and 94% for LTG and LEV, without significant differences. LTG and LEV were better tolerated than CBZ-CR. A network meta-analysis of these trials showed no difference between LEV and LTG for seizure freedom (OR: 0.86; 95% CI: 0.15-4.89), but demonstrated greater occurrence of adverse events for LEV than LTG (OR: 6.87; 95% CI: 1.15-41.1) (Brigo et al., 2018). A randomized double-blinded trial on AEDs in epileptic patients, aged 60 years and older (two thirds had cerebrovascular aetiology), demonstrated higher one-year retention rates for LEV (62%) compared to CBZ-CR (46%; p=0.02), while LTG (56%) was intermediate (Werhahn et al., 2015). The SANAD trial, a non-blinded randomized controlled study comparing five standard and new AEDs in focal epilepsy, found LTG to have the best retention rate as compared to carbamazepine (CBZ), gabapentin, oxcarbazepine, and topiramate (Marson et al., 2007). Although data were not stratified according to the underlying aetiology, the findings can likely be extrapolated to PSE. The non-blinded, randomized, 52-week KOMET study compared the effectiveness of LEV as monotherapy to extended-release sodium valproate (VPA-ER) or CBZ-CR after the physician had decided which of the two AEDs best suited the individual patient (Trinka et al., 2013). In a post-hoc subgroup analysis of patients aged ≥60 years with newly diagnosed epilepsy (most of which were likely to have cerebrovascular aetiology), the 12-month retention rates in the VPA-ER stratum were 90% in the LEV group and 77% in the VPA-ER group; the corresponding rates in the CBZ-CR stratum were 75% and 53% in the LEV and CBZ-CR treatment arms, respectively (Pohlmann-Eden et al., 2016). In summary, the findings from clinical studies argue in favour of the newer AEDs for PSE due to their better tolerability profiles.

In focal epilepsy, the underlying aetiology does not usually determine the choice of AED. The decision regarding the most suitable compound has to be individualized according to the patient’s age, sex, comorbidities and comedications. Patients with PSE likely carry some burden of cardiovascular risk factors. Accordingly, AEDs such as CBZ, phenytoin, phenobarbital and primidone, which can increase biochemical markers of vascular disease, including total cholesterol, lipoprotein, C-reactive protein and homocysteine (Mintzer et al., 2009), should be avoided. Being strong enzyme-inducers, these AEDs may also increase the metabolism, and thus decrease serum concentrations, of drugs that are concomitantly administered for stroke management, such as warfarin. Post-stroke depression is common, and the detrimental effects of LEV on behaviour (Josephson et al., 2019) may further fuel psychiatric comorbidity, rendering this AED less appropriate in patients with post-stroke depression.

The question to withdrawal the antiepileptic treatment at some time point after the onset of PSE is difficult to address. The overall risk of seizure recurrence within five years after AED tapering is roughly 50%. A meta-analysis on seizure recurrence rate after AED withdrawal, based on 10 retrospective, prospective and randomized-controlled trials involving more than 1,700 patients, allowed the development of a prediction tool for seizure relapse (Lamberink et al., 2017). This tool can be accessed online (Epilepsy Prediction and Tool., 2019) and can assist physicians, but the decision to withdraw the treatment needs to be tailored to each patient individually.


Several issues of PSE remain open to further research and investigation. Studies are warranted to elucidate the mechanisms of epileptogenesis after stroke and identify reliable biomarkers associated with the development of PSE. The role of EEG in predicting the occurrence of post-stroke seizures and epilepsy requires additional evaluation. The duration of EEG recording should be further evaluated in order to establish whether prolonged video-EEG monitoring during the first 72 hours after stroke is cost-effective and can offer advantages over routine, short-lasting EEG to identify post-stroke seizures (Grillo, 2015). The association of systemic thrombolysis and mechanical revascularization procedures with the development of early and late post-stroke seizures is still a matter of debate (Bentes et al., 2020). Similarly, there remain uncertainties about the most efficacious and safe AED to manage PSE.

Long-term, prospective, multicentric, high-quality studies with large cohorts of patients and stroke registries are needed to elaborate a practice guideline on diagnosis and treatment of PSE.


Summary didactic slides are available on the website.




Dr. Brigo received travel support from Eisai; acted as consultant for Eisai, LivaNova, and UCB Pharma; and was one of the organizers of the “Seizures & Stroke” Congress, held in Gothenburg from 20th to 22nd February 2019.

Dr Zelano has received consultancy fees from the Swedish Medial Product agency; speaker honoraria from UCB, was one of the organizers of the “Seizures & Stroke” Congress, held in Gothenburg from 20th to 22nd February 2019; and as an employee of Sahlgrenska university hospital (no personal compensation) is, and has been, an investigator in clinical trials sponsored by GW Pharma, SK life science, UCB, and Bial.

Dr. Holtkamp received speaker’s honoraria and/or consultancy fees from Bial, Desitin, Eisai, GW Pharmaceuticals, LivaNova, Novartis, and UCB (within the last three years).

Dr. Trinka received speaker honoraria from Eisai, UCB Pharma, LivaNova, Sandoz, Novartis, Biogen, Everpharma, BIAL-Portela &C, Newbridge, GL Pharma, Boehringer; grants from Biogen, UCB Pharma, Bayer, Novarti, Eisai, Merck, and Red Bull; grants from the European Union, FWF Österreichischer Fond zur Wissenschaftsforderung, Bundesministerium für Wissenschaft und Forschung, and Jubiläumsfond der Österreichischen Nationalbank outside the submitted work; and is a member of the following ILAE Task forces: Medical Therapies, Nosology, Terminology, Congresses, Driving, Regulatory affairs, and Telemedicine.

Dr. Agarwal and Dr. Lattanzi have no conflicts of interest to disclose.

via John Libbey Eurotext – Epileptic Disorders – How to diagnose and treat post-stroke seizures and epilepsy

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[BLOG POST] Driving and Epilepsy

For people with epilepsy, driving is a complex issue. Losing your license, trying to get it reinstated, and deciding whether it’s safe to drive can be frustrating and stressful. Some of us with epilepsy are unable to drive at all. It can help to talk about it with other people going through the same thing.

On MyEpilepsyTeam, the social network and online support group for those living with epilepsy, members talk about a range of personal experiences and struggles. Driving is one of the top 10 topics most discussed.

Here are some question-and-answer threads about driving:

• Do you guys drive?

• Does anyone have their license back after a year clear of tonic-clonic seizures?

• Do all types of seizures affect your ability to drive? Does anyone else still have their driver’s license?

Here are some conversations about driving:

• Birthdays are supposed to be cheerful, right? I feel epilepsy has held back my independence and my freedom to drive.

• A month ago I was in a near death auto accident because of a seizure.

• No seizures at all today. My hope is for one day I’ll be able to drive my first car. If it means not endangering myself and others I’ll be okay with never driving.

• I get really bad anxiety when someone mentions me driving. Have any of you had this problem? Is there anything that can be done about it?

Can you relate?

Have another topic you’d like to discuss or explore? Go to MyEpielpsyTeam today and start the conversation. You’ll be surprised just how many others may share similar stories.

Feel free to ask a question here.

Source: Mdpi


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[ARTICLE] Enhancing epilepsy self-management and quality of life for adults with epilepsy with varying social and educational backgrounds using PAUSE to Learn Your Epilepsy – Full Text


•PAUSE is a personalized epilepsy self-management (SM) education program.

•PAUSE was implemented in diverse and mostly underserved adults with epilepsy.

•Self-efficacy, frequency of SM behaviors, and QOL significantly improved over time.

•Personal negative impact of epilepsy significantly reduced over time.

•Greater improvement was seen in those with lower scores at baseline.



People with epilepsy (PWE) come from a wide variety of social backgrounds and educational skillsets, making self-management (SM) education for improving their condition challenging. Here, we evaluated whether a mobile technology-based personalized epilepsy SM education intervention, PAUSE to Learn Your Epilepsy (PAUSE), improves SM measures such as self-efficacy, epilepsy SM behaviors, epilepsy outcome expectations, quality of life (QOL), and personal impact of epilepsy in adults with epilepsy.


Recruitment for the PAUSE study occurred from October 2015 to March 2019. Ninety-one PWE were educated using an Internet-enabled computer tablet application that downloads custom, patient-specific educational programs from Validated self-reported questionnaires were used for outcome measures. Participants were assessed at baseline (T0), the first follow-up at completion of the PWE-paced 8–12-week SM education intervention (T1), and the second follow-up at least 3 months after the first follow-up (T2). Multiple linear regression was used to assess within-subject significant changes in outcome measures between these time points.


The study population was diverse and included individuals with a wide variety of SM educational needs and abilities. The median time for the first follow-up assessment (T1) was approximately 4 months following the baseline (T0) and 8 months following baseline for the second follow-up assessment (T2). Participants showed significant improvement in all SM behaviors, self-efficacy, outcome expectancy, QOL, and personal impact of epilepsy measures from T0 to T1. Participants who scored lower at baseline tended to show greater improvement at T1. Similarly, results showed that participant improvement was sustained in the majority of SM measures from T1 to T2.


This study demonstrated that a mobile technology-based personalized SM intervention is feasible to implement. The results provide evidence that epilepsy SM behavior and practices, QOL, outcome expectation for epilepsy treatment and management, self-efficacy, and outcome expectation and impact of epilepsy significantly improve following a personalized SM education intervention. This underscores a greater need for a pragmatic trial to test the effectiveness of personalized SM education, such as PAUSE to Learn Your Epilepsy, in broader settings specifically for the unique needs of the hard-to-reach and hard-to-treat population of PWE.

1. Introduction

Epilepsy, characterized by spontaneous recurrent seizures with unpredictable frequency, is a common and complex neurological disorder that affects the health and quality of life (QOL) of people with epilepsy (PWE) [1]. It is the fourth most common chronic neurological disorder after migraines, Alzheimer’s disease, and Parkinson’s disease in terms of 1-year prevalence per 1000 in the general population [2]. In 2015, approximately 1.2% of American adults reported living with epilepsy; 68.5% had seen a neurologist or epilepsy specialist; 93% were taking antiseizure medication (ASM), and, among those taking medication to control seizures, only 42.4% were seizure-free in the past year [3]. Epilepsy, especially with uncontrolled seizures, poses an immense burden to the people who have it, caregivers, and the society due to a number of factors including associated developmental, cognitive, and psychiatric comorbidities; ASM side effects; higher injury and mortality rates; poorer QOL; and increased financial burden. An estimated 3.0% of global disability-adjusted life years (DALYs) were from neurological disorders in 2010, a quarter of which were from epilepsy; epilepsy was the second-most burdensome chronic neurologic disorder worldwide in terms of DALYs [4].

Self-management (SM) education has shown to improve SM skills & behaviors and QOL in many chronic diseases including heart disease, diabetes, asthma, and arthritis [5,6]. Barlow defines self-management as an individual’s ability to manage the symptoms, treatments, physical and psychological consequences, and life style changes inherent in living with a chronic condition [7]. However, successful SM requires sufficient knowledge of the condition, its treatment, and necessary skills to perform SM activities. Like other chronic conditions, day-to-day management of epilepsy shifts from healthcare professionals to PWE. Epilepsy care demands active involvement of PWE in keeping up with the health effects of epilepsy and coping with social (e.g., family/friends, stigma, hobbies), health (e.g., seizure response/tracking, comorbidities such as depression/anxiety, sleep, safety, health literacy), employment (e.g., transportation, disability, absenteeism), and economic (e.g., cost of healthcare and medication) challenges. One can only self-manage their disease if they have the tools to do so, including knowledge, access to information relevant to their specific healthcare needs, and the ability to carry out the SM tasks needed for their condition. Evidence shows that many PWE are not knowledgeable about their disorder or often not educated about the risks of epilepsy, injury, and mortality [1,8]. Education needs also vary between individuals and subgroups of PWE. Women, in particular, may seek information on bone health and the effect of ASM on pregnancy or contraception, while older adults’ priorities may relate to fall safety and interactions of ASM with other medications. Existing evidence also reveals that, while patients with chronic diseases are willing to receive SM education materials, perceived information overload (i.e., too much or complex information) negatively influences their usage willingness [9]. Patients with low health literacy are even more susceptible to information overload [10]. The Institute of Medicine recognized SM education gaps for PWE and recommended (Recommendation 9) in its 2012 report, “Epilepsy Across the Spectrum: Promoting Health and Understanding,” to improve and expand educational opportunities for PWE and their families, as well as to ensure that all PWE and their families have access to accurate, clearly communicated educational materials and information [1].

Several studies have reported contradictory results after examining the efficacy of SM education interventions in improving PWE’s knowledge and understanding of epilepsy and QOL. The Modular Service Package Epilepsy study (MOSES) reported significant improvements in ASM tolerability, epilepsy knowledge, coping with epilepsy, and seizure frequency after 6 months following a 2-day SM education program [11]. Self-management education for people with poorly controlled epilepsy [SMILE (UK)] adapted MOSES for use in the United Kingdom and did not find the 2-day course to be effective in improving QOL or secondary outcome measures (anxiety and depression), after 12 months [12]. Though both MOSES and SMILE were randomized control trials (RCTs), MOSES included all adults with epilepsy whereas SMILE included only adults with chronic epilepsy who had two or more seizures in the prior 12 months. Another RCT compared the effectiveness of a multicomponent SM intervention consisting of five weekly, 2-hour group sessions each followed by a 2-hour group session after three weeks with usual care; they found no difference in measures of self-efficacy, though did find improvements in some epilepsy QOL domains and decreases in measures of ASM side effects [13]. Other studies examining the efficacy of in-person, group-based, online or phone/internet SM interventions, including the Centers for Disease Control and Prevention-supported Managing Epilepsy Well (MEW) network programs, did show improvement in epilepsy SM and QOL [[14][15][16][17][18]].

In addition to existing group-based programs, which require permission to use and specialized training, there is a greater need for patient-centered and patient-specific individualized education interventions for epilepsy SM that are publicly available, cost-effective, and easily disseminated to clinics or in community. The PAUSE to Learn Your Epilepsy (hereafter referred to as “PAUSE”), a MEW network collaboration center, was developed and implemented to address the needs of all PWE, especially those in underserved populations. This program uses publicly available education information from the Epilepsy Foundation (EF) website,, linked to a mobile technology-based PAUSE application to provide patient-centered personalized epilepsy SM lesson plan to PWE. Detailed information about PAUSE including study design, recruitment, intervention, and assessments has been published previously [19,20]. We reported significantly lower epilepsy SM practices and behaviors among PWE from an underserved population as compared to all PWE. In this paper, we sought to determine whether the PAUSE intervention significantly improves self-efficacy, SM behavior & skills, QOL, personal impact of epilepsy, and epilepsy outcome expectancies over time in adults with epilepsy. We also assessed whether perceived depression symptoms influence longitudinal changes in SM measures following the PAUSE intervention.[…]


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[WEB PAGE] Mozart may reduce seizure frequency in people with epilepsy

June 10, 2020. Source: University Health Network


A new clinical research study has found that a Mozart composition may reduce seizure frequency in patients with epilepsy.

A new clinical research study by Dr. Marjan Rafiee and Dr. Taufik Valiante of the Krembil Brain Institute at Toronto Western Hospital, part of University Health Network, has found that a Mozart composition may reduce seizure frequency in patients with epilepsy.

The results of the research study, “The Rhyme and Rhythm of Music in Epilepsy,” was recently published in the international journal Epilepsia Open. It looks at the effects of the Mozart melody, “Sonata for Two Pianos in D Major, K. 448” on reducing seizures, as compared to another auditory stimulus — a scrambled version of the original Mozart composition, with similar mathematical features, but shuffled randomly and lacking any rhythmicity.

“In the past 15 to 20 years, we have learned a lot about how listening to one of Mozart’s compositions in individuals with epilepsy appears to demonstrate a reduction in seizure frequency,” says Dr. Marjan Rafiee, lead author on the study. “But, one of the questions that still needed to be answered was whether individuals would show a similar reduction in seizure frequency by listening to another auditory stimulus — a control piece — as compared to Mozart.”

The researchers recruited 13 patients to participate in the novel, year-long study. After three months of a baseline period, half of the patients listened to Mozart’s Sonata once daily for three months, then switched to the scrambled version for three months. The others started the intervention by listening to the scrambled version for three months, then switched to daily listening of Mozart.

Patients kept “seizure diaries” to document their seizure frequency during the intervention. Their medications were kept unchanged during the course of the study.

“Our results showed daily listening to the first movement of Mozart K.448 was associated with reducing seizure frequency in adult individuals with epilepsy,” says Dr. Rafiee. “This suggests that daily Mozart listening may be considered as a supplemental therapeutic option to reduce seizures in individuals with epilepsy.”

Epilepsy is the most common serious neurological disorder in the world, affecting approximately 300,000 Canadians and 50 million people worldwide.

Many experience debilitating seizures. The treatment is often one or more anti-seizure medications. But for 30 per cent of patients, the medications are not effective in controlling their seizures.

“As a surgeon, I have the pleasure of seeing individuals benefit from surgery, however I also know well those individuals for whom surgery is not an option, or those who have not benefitted from surgery, so, we are always looking for ways to improve symptom control, and improve quality of life for those with epilepsy,” says Dr. Taufik Valiante, senior author of the study and the Director of the Surgical Epilepsy Program at Krembil Brain Institute at UHN and co-Director of CRANIA.

“Like all research, ours raises a lot of questions that we are excited to continue to answer with further research and support from the epilepsy community.”

While these results are promising, the next step is to conduct larger studies with more patients, over a longer period of time.

Story Source:

Materials provided by University Health NetworkNote: Content may be edited for style and length.

Journal Reference:

  1. Marjan Rafiee, Kramay Patel, David M. Groppe, Danielle M. Andrade, Eduard Bercovici, Esther Bui, Peter L. Carlen, Aylin Reid, Peter Tai, Donald Weaver, Richard Wennberg, Taufik A. Valiante. Daily listening to Mozart reduces seizures in individuals with epilepsy: A randomized control studyEpilepsia Open, 2020; 5 (2): 285 DOI: 10.1002/epi4.12400

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[Survey] Driving with an intracranial tumor

EAN Scientific Panel Neuro-oncology invites you to take part in their survey

Meningeomas and brain tumors may interfere with the ability to drive a vehicle in a number of ways. Seizures, cognitive impairment, motor dysfunction and visual field defects may all impair safe driving. Intracranial tumors are highly heterogenous, ranging from benign meningeomas that nevertheless may cause seizures, to high grade gliomas and brain metastasis. The clinician always considers seizure frequency, compliance and focal deficits when assessing the ability to drive for neurological patients. However, oncological prognosis, risk of recurrence and effects of treatment are factors unique to patients with intracranial tumors. These factors must be evaluated when deciding if or when a patient with a brain tumor or a meningeoma may drive. In addition, different medical professions may differ in awareness of the driving dilemma as well as in practice policy concerning this issue.

Clinical studies and reviews that address driving ability in patients with brain tumors are sparse. Most countries do not have national guidelines concerning this issue, and general as well as specific driving legislations vary between countries. In the absence of guidelines or legislation, most clinicians probably prohibit or allow driving on a case-by-case basis, or by adhering to legislation concerning epilepsy or neoplastic disease in general. The use of neuro-psychological evaluation or practical testing is unknown.

The EAN Scientific Panel of neuro-oncology wants to address this issue by performing a survey of national legislations and practice patterns among European neurologists. As a start, we aim to do a survey among the members of the Scientific Panels of Neuro-Oncology and Epilepsy.

The answers will be a guidance for whether there are inconsistences in clinical practice and reason to do a more extensive survey.


Thomas S1Mehta MPKuo JSIan Robins HKhuntia D. Current practices of driving restriction implementation for patients with brain tumors.
J Neurooncol.
 2011l;103(3):641-7. doi: 10.1007/s11060-010-0439-7.

Louie AV, D’Souza DP, Palma DA, Bauman GS, Lock M, Fisher B, Patil N, Rodrigues GB.

Fitness to drive in patients with brain tumours: the influence of mandatory reporting legislation on radiation oncologists in Canada.

Curr Oncol. 2012;19(3):e117-22. 

Chan E, Louie AV, Hanna M, Bauman GS, Fisher BJ, Palma DA, Rodrigues GB, Sathya A, D’Souza DP.

Multidisciplinary assessment of fitness to drive in brain tumour patients in southwestern Ontario: a grey matter.

Curr Oncol. 2013;20(1):e4-e12. doi: 10.3747/co.20.1198

Louie AV, Chan E, Hanna M, Bauman GS, Fisher BJ, Palma DA, Rodrigues GB, Warner A, D’Souza DP. Assessing fitness to drive in brain tumour patients: a grey matter of law, ethics, and medicine. Curr Oncol. 2013;20(2):90-6.

Mansur A1,2Desimone A2Vaughan S2Schweizer TA1,2,3Das S. To drive or not to drive, that is still the question: current challenges in driving recommendations for patients with brain tumours. J Neurooncol. 2018;137(2):379-385. doi: 10.1007/s11060-017-2727-y.

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[ARTICLE] Cognition and epilepsy. Cognitive screening test – Full Text PDF


Cognitive: deficits often occur in people with epilepsy (PWE). However, in Brazil, PWE might not undergo neurocognitive evaluation due to the low number of validated tests available and lack of multidisciplinary teams in general epilepsy outpatient clinics.

Objective: To correlate Brief Cognitive Battery-Edu (BCB-Edu) scores with epilepsy characteristics of 371 PWE.

Methods: Clinical and cognitive assessment (MMSE, BCB-Edu) of 371 PWE aged >18 years was performed. The clinical aspects of epilepsy were correlated with BCB-Edu data. Cognitive data of PWE were compared against those of 95 healthy individuals (NC), with p-<0.05.

Results: People with epilepsy had lower cognitive performance than individuals in the NC group. Cognitive aspects also differed according to epilepsy characteristics. Predictive factors for impairment in multiple cognitive domains were age and use of more than one antiepileptic drug (logistic regression; R2 Nagelkerke=0.135).

Conclusion: Worse cognitive performance was found in PWE on different domains. There was a relationship between cognitive impairment and the aspects of epilepsy. BCB-Edu proved to be effective as a cognitive assessment screening test for epilepsy in adults. Key words: epilepsy, Brief Cognitive Battery-Edu, cognition[…]

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[Abstract + References] Antidepressant effect of vagal nerve stimulation in epilepsy patients: a systematic review



Vagal nerve stimulation (VNS) is an effective palliative therapy in drug-resistant epileptic patients and is also approved as a therapy for treatment-resistant depression. Depression is a frequent comorbidity in epilepsy and it affects the quality of life of patients more than the seizure frequency itself. The aim of this systematic review is to analyze the available literature about the VNS effect on depressive symptoms in epileptic patients.

Material and methods

A comprehensive search of PubMed, Medline, Scopus, and Google Scholar was performed, and results were included up to January 2020. All studies concerning depressive symptom assessment in epileptic patients treated with VNS were included.


Nine studies were included because they fulfilled inclusion criteria. Six out of nine papers reported a positive effect of VNS on depressive symptoms. Eight out of nine studies did not find any correlation between seizure reduction and depressive symptom amelioration, as induced by VNS. Clinical scales for depression, drug regimens, and age of patients were broadly different among the examined studies.


Reviewed studies strongly suggest that VNS ameliorates depressive symptoms in drug-resistant epileptic patients and that the VNS effect on depression is uncorrelated to seizure response. However, more rigorous studies addressing this issue are encouraged.


  1. 1.Chen Z, Brodie MJ, Liew D, Kwan P (2018) Treatment outcomes in patients with newly diagnosed epilepsy treated with established and new antiepileptic drugs a 30-year longitudinal cohort study. JAMA Neurol 75:279–286. PubMed Google Scholar 
  2. 2.Spencer S, Huh L (2008) Outcomes of epilepsy surgery in adults and children. Lancet Neurol 7:525–537Article Google Scholar 
  3. 3.De Tisi J, Bell GS, Peacock JL et al (2011) The long-term outcome of adult epilepsy surgery, patterns of seizure remission, and relapse: a cohort study. Lancet 378:1388–1395. PubMed Google Scholar 
  4. 4.Rathore C, Radhakrishnan K (2015) Concept of epilepsy surgery and presurgical evaluation. In: Epileptic disorders
  5. 5.Benbadis SR, Geller E, Ryvlin P, Schachter S, Wheless J, Doyle W, Vale FL (2018) Putting it all together: options for intractable epilepsy. Epilepsy Behav 88:33–38. Google Scholar 
  6. 6.Ben-Menachem E, Mañon-Espaillat R, Ristanovic R et al (1994) Vagus nerve stimulation for treatment of partial seizures: 1. A controlled study of effect on seizures. Epilepsia 35:616–626. Article PubMed Google Scholar 
  7. 7.George R, Salinsky M, Kuzniecky R et al (1994) Vagus nerve stimulation for treatment of partial seizures: 3. Long-term follow-up on first 67 patients exiting a controlled study. Epilepsia.
  8. 8.Elliott RE, Morsi A, Kalhorn SP, Marcus J, Sellin J, Kang M, Silverberg A, Rivera E, Geller E, Carlson C, Devinsky O, Doyle WK (2011) Vagus nerve stimulation in 436 consecutive patients with treatment-resistant epilepsy: long-term outcomes and predictors of response. Epilepsy Behav 20:57–63. PubMed Google Scholar 
  9. 9.Orosz I, McCormick D, Zamponi N, Varadkar S, Feucht M, Parain D, Griens R, Vallée L, Boon P, Rittey C, Jayewardene AK, Bunker M, Arzimanoglou A, Lagae L (2014) Vagus nerve stimulation for drug-resistant epilepsy: a European long-term study up to 24 months in 347 children. Epilepsia 55:1576–1584. PubMed Google Scholar 
  10. 10.Helmers SL, Wheless JW, Frost M, Gates J, Levisohn P, Tardo C, Conry JA, Yalnizoglu D, Madsen JR (2001) Vagus nerve stimulation therapy in pediatric patients with refractory epilepsy: retrospective study. J Child Neurol 16:843–848. Article PubMed Google Scholar 
  11. 11.Boylan LS, Flint LA, Labovitz DL, Jackson SC, Starner K, Devinsky O (2004) Depression but not seizure frequency predicts quality of life in treatment-resistant epilepsy. Neurology 62:258–261. Article PubMed Google Scholar 
  12. 12.Kim M, Kim Y-S, Kim D-H, Yang TW, Kwon OY (2018) Major depressive disorder in epilepsy clinics: a meta-analysis. Epilepsy Behav 84:56–69. PubMed Google Scholar 
  13. 13.Ajinkya S, Fox J, Lekoubou A (2020) Trends in prevalence and treatment of depressive symptoms in adult patients with epilepsy in the United States. Epilepsy Behav 105:106973. PubMed Google Scholar 
  14. 14.Tombini M, Assenza G, Quintiliani L, Ricci L, Lanzone J, Ulivi M, di Lazzaro V (2020) Depressive symptoms and difficulties in emotion regulation in adult patients with epilepsy: association with quality of life and stigma. Epilepsy Behav 107:107073Article Google Scholar 
  15. 15.Yuan T-F, Li A, Sun X, Arias-Carrión O, Machado S (2016) Vagus nerve stimulation in treating depression: a tale of two stories. Curr Mol Med 16:33–39. Article PubMed Google Scholar 
  16. 16.Harden CL, Pulver MC, Ravdin LD, Nikolov B, Halper JP, Labar DR (2000) A pilot study of mood in epilepsy patients treated with vagus nerve stimulation. Epilepsy Behav 1:93–99. PubMed Google Scholar 
  17. 17.Elger G, Hoppe C, Falkai P, Rush AJ, Elger CE (2000) Vagus nerve stimulation is associated with mood improvements in epilepsy patients. Epilepsy Res 42:203–210. Article PubMed Google Scholar 
  18. 18.Rush AJ, Marangell LB, Sackeim HA, George MS, Brannan SK, Davis SM, Howland R, Kling MA, Rittberg BR, Burke WJ, Rapaport MH, Zajecka J, Nierenberg AA, Husain MM, Ginsberg D, Cooke RG (2005) Vagus nerve stimulation for treatment-resistant depression: a randomized, controlled acute phase trial. Biol Psychiatry 58:347–354. PubMed Google Scholar 
  19. 19.Rush AJ, George MS, Sackeim HA, Marangell LB, Husain MM, Giller C, Nahas Z, Haines S, Simpson RK Jr, Goodman R (2000) Vagus nerve stimulation (VNS) for treatment-resistant depressions: a multicenter study∗∗See accompanying Editorial, in this issue. Biol Psychiatry 47:276–286. Article PubMed Google Scholar 
  20. 20.Rush AJ, Sackeim HA, Marangell LB, George MS, Brannan SK, Davis SM, Lavori P, Howland R, Kling MA, Rittberg B, Carpenter L, Ninan P, Moreno F, Schwartz T, Conway C, Burke M, Barry JJ (2005) Effects of 12 months of vagus nerve stimulation in treatment-resistant depression: a naturalistic study. Biol Psychiatry 58:355–363. PubMed Google Scholar 
  21. 21.Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JPA, Clarke M, Devereaux PJ, Kleijnen J, Moher D (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin Epidemiol 62:e1–e34. PubMed Google Scholar 
  22. 22.Klinkenberg S, van den Bosch CNCJ, Majoie HJM, Aalbers MW, Leenen L, Hendriksen J, Cornips EMJ, Rijkers K, Vles JSH, Aldenkamp AP (2013) Behavioural and cognitive effects during vagus nerve stimulation in children with intractable epilepsy–a randomized controlled trial. Eur J Paediatr Neurol 17:82–90. PubMed Google Scholar 
  23. 23.Ryvlin P, Gilliam FG, Nguyen DK, Colicchio G, Iudice A, Tinuper P, Zamponi N, Aguglia U, Wagner L, Minotti L, Stefan H, Boon P, Sadler M, Benna P, Raman P, Perucca E (2014) The long-term effect of vagus nerve stimulation on quality of life in patients with pharmacoresistant focal epilepsy: the PuLsE (Open Prospective Randomized Long-term Effectiveness) trial. Epilepsia 55:893–900. Article PubMed Google Scholar 
  24. 24.Radloff LS (1977) The CES-D Scale. Appl Psychol Meas 1:385–401. Google Scholar 
  25. 25.Gilliam FG, Barry JJ, Hermann BP, Meador KJ, Vahle V, Kanner AM (2006) Rapid detection of major depression in epilepsy: a multicentre study. Lancet Neurol 5:399–405. PubMed Google Scholar 
  26. 26.Klinkenberg S, Majoie HJM, Van Der Heijden MMAA et al (2012) Vagus nerve stimulation has a positive effect on mood in patients with refractory epilepsy. Clin Neurol Neurosurg 114:336–340. Article PubMed Google Scholar 
  27. 27.Chavel SM, Westerveld M, Spencer S (2003) Long-term outcome of vagus nerve stimulation for refractory partial epilepsy. Epilepsy Behav 4:302–309. PubMed Google Scholar 
  28. 28.Hoppe C, Helmstaedter C, Scherrmann J, Elger CE (2001) Self-reported mood changes following 6 months of vagus nerve stimulation in epilepsy patients. Epilepsy Behav 2:335–342. Article PubMed Google Scholar 
  29. 29.Hallböök T, Lundgren J, Stjernqvist K, Blennow G, Strömblad LG, Rosén I (2005) Vagus nerve stimulation in 15 children with therapy resistant epilepsy; its impact on cognition, quality of life, behaviour and mood. Seizure 14:504–513. PubMed Google Scholar 
  30. 30.Spindler P, Bohlmann K, Straub H-B, Vajkoczy P, Schneider UC (2019) Effects of vagus nerve stimulation on symptoms of depression in patients with difficult-to-treat epilepsy. Seizure 69:77–79. PubMed Google Scholar 
  31. 31.Ettinger AB, Weisbrot DM, Nolan EE, Gadow KD, Vitale SA, Andriola MR, Lenn NJ, Novak GP, Hermann BP (1998) Symptoms of depression and anxiety in pediatric epilepsy patients. Epilepsia 39:595–599. Article PubMed Google Scholar 
  32. 32.Kerr MP, Mensah S, Besag F, de Toffol B, Ettinger A, Kanemoto K, Kanner A, Kemp S, Krishnamoorthy E, LaFrance WC Jr, Mula M, Schmitz B, van Elst L, Trollor J, Wilson SJ, International League of Epilepsy (ILAE) Commission on the Neuropsychiatric Aspects of Epilepsy (2011) International consensus clinical practice statements for the treatment of neuropsychiatric conditions associated with epilepsy. Epilepsia 52:2133–2138. PubMed Google Scholar 
  33. 33.Tombini M, Assenza G, Quintiliani L, Ricci L, Lanzone J, de Mojà R, Ulivi M, di Lazzaro V (2019) Epilepsy-associated stigma from the perspective of people with epilepsy and the community in Italy. Epilepsy Behav 98:66–72. PubMed Google Scholar 
  34. 34.Dussaule C, Bouilleret V (2018) Psychiatric effects of antiepileptic drugs in adults. Gériatrie Psychol Neuropsychiatr du Viellissement 16:181–188. Google Scholar 
  35. 35.Pisani LR, Nikanorova M, Landmark CJ, Johannessen SI, Pisani F (2018) Specific patient features affect antiepileptic drug therapy decisions: focus on gender, age, and psychiatric comorbidities. Curr Pharm Des 23:5639–5648. Article Google Scholar 
  36. 36.Assenza G, Lanzone J, Dubbioso R et al (2020) Thalamic and cortical hyperexcitability in juvenile myoclonic epilepsy. Clin Neurophysiol
  37. 37.Pellegrino G, Mecarelli O, Pulitano P, Tombini M, Ricci L, Lanzone J, Brienza M, Davassi C, di Lazzaro V, Assenza G (2018) Eslicarbazepine acetate modulates EEG activity and connectivity in focal epilepsy. Front Neurol 9.
  38. 38.Rolle CE, Fonzo GA, Wu W, Toll R, Jha MK, Cooper C, Chin-Fatt C, Pizzagalli DA, Trombello JM, Deckersbach T, Fava M, Weissman MM, Trivedi MH, Etkin A (2020) Cortical connectivity moderators of antidepressant vs placebo treatment response in major depressive disorder. JAMA Psychiatry 94305:397. Google Scholar 
  39. 39.Vecchio F, Miraglia F, Curcio G, Della Marca G, Vollono C, Mazzucchi E, Bramanti P, Rossini PM (2015) Cortical connectivity in fronto-temporal focal epilepsy from EEG analysis: a study via graph theory. Clin Neurophysiol 126:1108–1116. PubMed Google Scholar 
  40. 40.Vecchio F, Miraglia F, Curcio G, Altavilla R, Scrascia F, Giambattistelli F, Quattrocchi CC, Bramanti P, Vernieri F, Rossini PM (2015) Cortical brain connectivity evaluated by graph theory in dementia: a correlation study between functional and structural data. J Alzheimers Dis 45:745–756. PubMed Google Scholar 
  41. 41.Parker CS, Clayden JD, Cardoso MJ, Rodionov R, Duncan JS, Scott C, Diehl B, Ourselin S (2018) Structural and effective connectivity in focal epilepsy. NeuroImage Clin 17:943–952. PubMed Google Scholar 
  42. 42.Saletu B, Anderer P, Saletu-Zyhlarz GM (2010) EEG topography and tomography (LORETA) in diagnosis and pharmacotherapy of depression. Clin EEG Neurosci 41:203–210CAS Article Google Scholar 
  43. 43.Zhdanov A, Atluri S, Wong W, Vaghei Y, Daskalakis ZJ, Blumberger DM, Frey BN, Giacobbe P, Lam RW, Milev R, Mueller DJ, Turecki G, Parikh SV, Rotzinger S, Soares CN, Brenner CA, Vila-Rodriguez F, McAndrews MP, Kleffner K, Alonso-Prieto E, Arnott SR, Foster JA, Strother SC, Uher R, Kennedy SH, Farzan F (2020) Use of machine learning for predicting escitalopram treatment outcome from electroencephalography recordings in adult patients with depression. JAMA Netw Open 3:e1918377–e1918377Article Google Scholar 
  44. 44.Romero-Osorio Ó, Gil-Tamayo S, Nariño D, Rosselli D (2018) Changes in sleep patterns after vagus nerve stimulation, deep brain stimulation or epilepsy surgery: systematic review of the literature. Seizure 56:4–8. PubMed Google Scholar 
  45. 45.Murray BJ, Matheson JK, Scammell TE (2001) Effects of vagus nerve stimulation on respiration during sleep. Neurology 57:1523–1524CAS Article Google Scholar 
  46. 46.Benca RM, Obermeyer WH, Thisted RA, Gillin JC (1992) Sleep and psychiatric disorders: a meta-analysis. Arch Gen Psychiatry 49:651–668CAS Article Google Scholar 
  47. 47.Wu JC, Bunney WE (1990) The biological basis of an antidepressant response to sleep deprivation and relapse: review and hypothesis. Am J Psychiatry
  48. 48.Tononi G, Cirelli C (2012) Time to be SHY? Some comments on sleep and synaptic homeostasis. Neural Plast 2012:1–12. Google Scholar 
  49. 49.Assenza G, Pellegrino G, Tombini M, di Pino G, di Lazzaro V (2013) Delta waves increase after cortical plasticity induction during wakefulness. Clin Neurophysiol 124:e71–e72. Google Scholar 
  50. 50.Assenza G, Di Lazzaro V (2015) A useful electroencephalography (EEG) marker of brain plasticity: delta waves. Neural Regen Res 10:1216–1217. PubMed Google Scholar 
  51. 51.Wolf E, Kuhn M, Normann C, Mainberger F, Maier JG, Maywald S, Bredl A, Klöppel S, Biber K, van Calker D, Riemann D, Sterr A, Nissen C (2016) Synaptic plasticity model of therapeutic sleep deprivation in major depression. Sleep Med Rev 30:53–62Article Google Scholar 
  52. 52.Sanacora G, Zarate CA, Krystal JH, Manji HK (2008) Targeting the glutamatergic system to develop novel, improved therapeutics for mood disorders. Nat Rev Drug Discov 7:426–437CAS Article Google Scholar 
  53. 53.Di Pino G, Pellegrino G, Capone F et al (2016) Val66Met BDNF polymorphism implies a different way to recover from stroke rather than a worse overall recoverability. Neurorehabil Neural Repair 30:3–8. PubMed Google Scholar 
  54. 54.Sen S, Duman R, Sanacora G (2008) Serum brain-derived neurotrophic factor, depression, and antidepressant medications: meta-analyses and implications. Biol Psychiatry 64:527–532CAS Article Google Scholar 
  55. 55.Goldschmied JR, Gehrman P (2019) An integrated model of slow-wave activity and neuroplasticity impairments in major depressive disorder. Curr Psychiatry Rep 21:30Article Google Scholar 
  56. 56.O’Leary OF, Ogbonnaya ES, Felice D et al (2018) The vagus nerve modulates BDNF expression and neurogenesis in the hippocampus. Eur Neuropsychopharmacol 28:307–316. Article PubMed Google Scholar 
  57. 57.Lang UE, Bajbouj M, Gallinat J, Hellweg R (2006) Brain-derived neurotrophic factor serum concentrations in depressive patients during vagus nerve stimulation and repetitive transcranial magnetic stimulation. Psychopharmacology 187:56–59. Article PubMed Google Scholar 
  58. 58.Hays SA, Rennaker RL, Kilgard MP (2013) Targeting plasticity with vagus nerve stimulation to treat neurological disease. Progress in brain research. Elsevier, In, pp 275–299Google Scholar 
  59. 59.Capone F, Assenza G, Di Pino G et al (2015) The effect of transcutaneous vagus nerve stimulation on cortical excitability. J Neural Transm 122:679–685. PubMed Google Scholar 
  60. 60.Kimberley TJ, Prudente CN, Engineer ND, Pierce D, Tarver B, Cramer SC, Dickie DA, Dawson J (2019) Study protocol for a pivotal randomised study assessing vagus nerve stimulation during rehabilitation for improved upper limb motor function after stroke. Eur Stroke J 4:363–377Article Google Scholar 


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[ARTICLE] Prediction of the Recurrence Risk in Patients With Epilepsy After the Withdrawal of Antiepileptic Drugs – Full Text PDF


Many seizure-free patients who consider withdrawing from antiepileptic drugs (AEDs) hope to discontinue treatment to avoid adverse effects. However, withdrawal has certain risks that are difficult to predict. In this study, we performed a literature review, summarized the causes of significant variability in the risk of postwithdrawal recurrent seizures, and reviewed study data on the age at onset, cause, types of seizures, epilepsy syndrome, magnetic resonance imaging (MRI) abnormalities, epilepsy surgery, and withdrawal outcomes of patients with epilepsy. Many factors are associated with recurrent seizures after AED withdrawal. For patients who are seizure-free after treatment, the role of an electroencephalogram (EEG) alone in ensuring safe withdrawal is limited. A series of prediction models for the postwithdrawal recurrence risk have incorporated various potentially important factors in a comprehensive analysis. We focused on the populations of studies investigating five risk prediction models and analyzed the predictive variables and recommended applications of each model, aiming to provide a reference for personalized withdrawal for patients with epilepsy in clinical practice.

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[Abstract] Epilepsy after severe traumatic brain injury: frequency and injury severity



To estimate national frequency of posttraumatic epilepsy (PTE) after severe traumatic brain injury (TBI) and assess injury severity (Glasgow Coma Scale (GCS) and posttraumatic amnesia (PTA)) as prognostic factors for PTE.


Data on patients ≥18 years surviving severe TBI 2004–2016 were retrieved from the Danish Head Trauma Database (n = 1010). The cumulative incidence proportion (CIP) was estimated using death as competing event. The association between injury severity and PTE was assessed using multivariable competing risk regressions.


CIP of PTE 28 days and one year post-TBI was 6.8% (95% confidence interval (CI) 5.4–8.5) and 18.5% (95% CI 16.1–21.1%), respectively. Injury severity was not associated with PTE within 28 days post-TBI but indicated higher PTE-rates in less severely injured patients. PTA-duration >70 days was associated with PTE 29–365 days post-TBI (Adjusted sub-hazard ratio 4.23 (95% CI 1.79–9.99)). GCS was not associated with PTE 29–365 days post-TBI.


The PTE frequency was higher compared to previous estimates. Increasing injury severity was associated with PTE 29–365 days post-TBI when measured with PTA, but not with GCS. Though nonsignificant, the increased PTE-risk within 28 days in lower severity suggests an underdiagnosing of PTE.


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[Infographic] What to Expect During VNS Implantation

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