**2.1 Definition of NCSE and AMS**

*Epilepsy - Advances in Diagnosis and Therapy*

Lethargy and confusion attributed to a postictal state Ictal confusion mistaken for metabolic encephalopathy Unresponsiveness and catalepsy presumed to be psychogenic Obtundation thought to be due to alcohol or drug intoxication Hallucinations and agitation mistaken for psychosis or delirium

Lethargy presumed secondary to hypoglycemia

Laughing and crying ascribed to emotional lability

*Examples of delayed or missed NCSE diagnosis; from Kaplan [48].*

Mutism attributed to aphasia

**Table 1.**

symptoms associated with underlying pathology such as posthypoxic, metabolic or septic encephalopathies, and the effects of sedative drugs. Furthermore, the diagnosis of NCSE is frequently delayed, with patients in the ICU having often other serious medical conditions. To diagnose NCSE a high degree of suspicion is required [2], and consequently NCSE remains unrecognized. **Table 1** shows how frequently the

In the United States, the estimated incidence of status epilepticus (SE) is 15–20/100,000 cases per year [3], and NCSE is representing 63% of all SE [4]. Both nonconvulsive seizures (NCS) and NCSE occur very frequently in the ICU and emergency department (ED): NCSs/NCSE is recorded in 8% to 48% in ICU patients

Prevalence of NCSE is reported from different geographical areas of the world in patients with AMS [12–16]; However, to our knowledge, there is no study reporting the frequency of NCSE in the Middle East and North Africa (MENA) region; in this vast geographic area, the only NCSE incidence/prevalence is described from the MENA's neighboring countries like Pakistan, India, Turkey, and Israel [17–21]. There is a need for studies regarding the prevalence and morbidity of NCSE in MENA countries [22]. There is also a lack of consensus regarding the EEG monitoring duration when looking for NCSE in ICU patients with AMS; the authors dealing with this issue report a considerable variation in the duration of cEEG monitoring [23–26].

a.Know the rate of occurrence of NCSE in patients with AMS admitted to Hamad

b.Describe the clinical and EEG findings, causes, head CT/MRI, as well as the treatment and outcomes of NCSE in patients with AMS, and compare the results to a matched control group with similar clinical presentations of AMS.

c.Highlight and discuss the lack of consensus in the literature regarding the duration of cEEG monitoring while looking for NCSs/NCSE in patients with AMS.

This clinical study was performed according to the Good Clinical Practice (GCP)

Committee and Institutional Review Board (IRB). All subjects/relative(s) (caregivers)

guidelines. Approval was obtained from Hamad Medical Corporation Ethical

General Hospital (HGH) Doha, Qatar, using cEEG monitoring.

diagnosis of NCSE could be missed in the emergency room.

[5–8], many of which are fatal [9–11].

The aims of this chapter are multiple:

provided consent before participating.

**46**

**2. Methods**

NCSE was defined as an AMS with diminished responsiveness, a positive EEG. and a response to anti-seizure drug (ASD) therapy; as a status, NCSE should be present for a minimum of 30 minutes of continuous nonconvulsive seizure activity or after repeated seizures without recovery of consciousness between events [1]; recently shorter durations have been reported.

Young's criteria [27] of electrographic SE and modified criteria of Chong and Hirsch [28] were used to diagnose NCSE; In addition, the International League against Epilepsy (ILAE) definition and classification of Status Epilepticus [29] and EEG Salzburg Consensus Criteria for NCSE [30] were used to recognize NCSE; NCSE was diagnosed in the presence of continuous generalized spike wave discharges with changes in intensity or frequency, epileptiform activity with ictal patterns that wax and wane, rhythmic and periodic discharges, and subtle and discrete electrographic seizures, when lasting for 30 minutes [10, 13, 15]. In comatose patients, epileptiform discharges faster than 2.5 Hz or generalized periodic discharges (GPDs), lateralized periodic discharges (LPDs) and continuous 2/s GPDs with triphasic morphology [31] of less than 2.5 Hz, as well as rhythmic discharges (RDs) faster than 0.5 Hz were also taken into consideration as NCSE if they responded to benzodiazepine treatment with improvement in the EEG or in patient mental status [13, 15, 29, 32].

Two EEG specialists agreed independently that the patient condition and EEG findings represent NCSE particularly when an EEG pattern did not meet above criteria; finally NCSE was considered if the EEG/or level of consciousness responded to an ASD trial.

Unexplained confusional state, change in behavior, mild to moderate obtundation, alteration in cognition and behavior from baseline, and unexplained decrease in level of consciousness including after convulsive status epilepticus treatment [2, 33] were considered AMS; in elderly patients, delirium (altered level of consciousness, with a fluctuating course, disorganized thinking, and inattention) was also included [15].

### **2.2 Patient selection for cEEG monitoring**

All patients with AMS, from the Emergency Department and from ICUs, aged 12 years or above, had a cEEG monitoring [2, 33]. Not included were patients with open head injury, those whose relatives did not sign the consent form and patients with suspected brain death and an isoelectric EEG. In addition, patients treated for convulsive status epilepticus (CSE) who did not develop later NCSs/NCSE on cEEG monitoring were excluded.

### **2.3 Patients with NCSE and control group**

Patients with AMS and those whose EEG was not compatible with NCSE during 3 days of cEEG monitoring recording were taken as controls. The NCSE and control groups were compared: this included the clinical presentation and medical condition, AMS etiology, neuroimaging, laboratory findings, length of stay, recovery, and outcome

### **2.4 cEEG monitoring and duration**

### *2.4.1 cEEG recording*

The following EEG recording system was used: international 10/20 system with 21 silver/silver chloride cup electrodes. Digital EEG signal stored electronically was filtered for display. High-pass filter and low-pass filter were 0.5–1 and 70 Hz. For

extraneous electrical artifact, 50 Hz notch filter was used; impedance was 100 and 5000 ohms. cEEG was done by EEG technologists and monitored at least twice a day by an EEG specialist.

## *2.4.2 EEG duration*

The duration of cEEG monitoring was determined by the response to treatment of NCSs/NCSE, the presence of other EEG features like rhythmic and periodic discharges, and their responses to treatment.

### **2.5 Laboratory investigations and Neuroimaging**

The following investigations were performed in most NCSE cases and controls: complete blood count, electrolytes, liver and renal functions, brain MRI, and/or CT head; imaging was performed either before or after cEEG monitoring

### **2.6 NCSs/NCSE treatment**

Benzodiazepines (lorazepam or diazepam) were used when NCSs/NCSE was suspected. If seizures persisted, European Federation of Neurological Sciences (EFNS) Guidelines and Glauser et al. report on NCSE treatment were followed: IV diazepam or lorazepam first and then second-line ASDs were initiated—valproic acid, phenytoin, or levetiracetam. If no results, continuous infusions of propofol, midazolam, and barbiturates were used [34, 35].

Many patients received more than one ASD. refractory NCSE was treated with anesthetic agents; same treatment protocol was followed in comatose NCSE. ASDs were not used in control group.

### **2.7 Outcome parameters**

Seizure control and survival/death were considered as primary outcome parameters, while complete recovery and length of stay were secondary outcome parameters.

### **2.8 Statistical methods**

Descriptive statistics (mean with standard deviation) for continuous variables, frequency, and percentages for categorical variables was used; differences between mean levels of NCSE and controls, outcome and morbidity, and Student's t-test were calculated; to detect associations between categorical variables and NCSE vs controls, outcome, and morbidity, chi-square tests or Fisher's exact tests were used. For independent variables at univariate analysis, NCSE logistic regressions were performed using a significance level of 0.05. A P value of 0.05 (two tailed) was considered a statistically significant level. For statistical analysis, an SPSS 22.0 statistical software was used.
