**3.8 EEG patterns and location**

EEG patterns recorded in the NCSE patients (n = 65): focal spike/sharp and wave >3/s in 43% (n = 28), generalized spike/sharp and wave >3/s in 28% (n = 18), GDPs, LPDs, continuous 2/s GPDs with triphasic morphology in 25% (n = 16), and multifocal spikes in 4% (n = 3); **Figures 1–5** show NCSE EEGs cases before and after ASD treatment.

**57**

**4. Discussion**

**Figure 5.**

**4.1 NCSE prevalence**

**4.2 NCSE outcome**

*Nonconvulsive Status Epilepticus in Patients with Altered Mental Status Admitted to Hamad…*

EEG in NCSE patients who ultimately died (n = 20): 40% periodic patterns (n = 8), 30% continuous generalized spike/sharp and waves (n = 6), and 30% with focal spike/sharp and waves (n = 6). Fifty-two percent (n = 34) showed a continuous ictal pattern, and forty-three percent (n = 28) an intermittent/recurrent ictal pattern; five percent (n = 3) were not classified; forty-six percent (n = 30) showed a focal onset and 29% (n = 19) a generalized onset; twenty-five percent (n = 16) showed a periodic pattern; focal seizures originated from the temporal areas (55%) and from the frontal areas (31%). In the control group (n = 185), focal/generalized slowing was seen in 43% (n = 80) and slowing with some spike/sharp wave activity in 2% (n = 4).

*(a) (Comatose focal NCSE) 67 years old male comatose, following head injury. EEG shows abnormal fast activity starting in right fronto-temporal leads accompanied by abnormal eye movements and facial twitching. (b) The ictal fast activity spreads to the contralateral fronto-temporal leads; patient shows same clinical manifestations (discrete twitching of the left face); the abnormal electrical activity was continuous for more than 30 mn. (c) 1 minute following 2 mg of lorazepam IV; patient remains comatose; EEG shows diffuse generalized slowing; no epileptiform activity; no clinical manifestations; survived with memory impairment and left hemiplegia.*

In the current longitudinal prospective hospital-based study, we investigated the frequency of NCSE in patients with AMS admitted to Hamad Hospital, Doha, Qatar. The prevalence of NCSE among patients with AMS was 26% at our center that is compatible with previous similar studies (prevalence = 16–37%) (**Table 6**); these researchers used a similar design, with a parallel control group; however, most were retrospective, the cEEG recording duration often shorter or not mentioned. Five other authors from MENA' s neighboring countries (mentioned in Section 1) also reported the prevalence of NCSE in patients with AMS; however, they used different study designs, and therefore, those studies cannot be compared with our study.

NCSE is often associated with a poor outcome and a high mortality rate [9, 12, 13, 38]. In the current study, the mortality rate among patients with AMS and

*DOI: http://dx.doi.org/10.5772/intechopen.83580*

*Nonconvulsive Status Epilepticus in Patients with Altered Mental Status Admitted to Hamad… DOI: http://dx.doi.org/10.5772/intechopen.83580*

### **Figure 5.**

*Epilepsy - Advances in Diagnosis and Therapy*

Thirty-two percent of patients with NCSE (n = 21, m 13, f 8) suffered from refractory NCSE, defined as seizures lasting more than 60 minutes with failure of two ASDs [37]; they received the following treatment: midazolam IV (n = 10), propofol (n = 5), thiopental (n = 4), and fentanyl (n = 2). Fifty-seven percent (n = 12, m 8, f 4) survived; forty-three percent (n = 9, m 5, f 4) died with the following reasons: cardiac arrest (3), sepsis (3), ischemia (1), subarachnoid hemorrhage (1),

EEG patterns recorded in the NCSE patients (n = 65): focal spike/sharp and wave >3/s in 43% (n = 28), generalized spike/sharp and wave >3/s in 28% (n = 18), GDPs, LPDs, continuous 2/s GPDs with triphasic morphology in 25% (n = 16), and multifocal spikes in 4% (n = 3); **Figures 1–5** show NCSE EEGs cases before and after ASD treatment.

and cerebral abscess (1). Only 33% (n = 7, m 4, f 3) recovered completely.

**3.7 Refractory NCSE**

**3.8 EEG patterns and location**

**56**

*(a) (Comatose focal NCSE) 67 years old male comatose, following head injury. EEG shows abnormal fast activity starting in right fronto-temporal leads accompanied by abnormal eye movements and facial twitching. (b) The ictal fast activity spreads to the contralateral fronto-temporal leads; patient shows same clinical manifestations (discrete twitching of the left face); the abnormal electrical activity was continuous for more than 30 mn. (c) 1 minute following 2 mg of lorazepam IV; patient remains comatose; EEG shows diffuse generalized slowing; no epileptiform activity; no clinical manifestations; survived with memory impairment and left hemiplegia.*

EEG in NCSE patients who ultimately died (n = 20): 40% periodic patterns (n = 8), 30% continuous generalized spike/sharp and waves (n = 6), and 30% with focal spike/sharp and waves (n = 6). Fifty-two percent (n = 34) showed a continuous ictal pattern, and forty-three percent (n = 28) an intermittent/recurrent ictal pattern; five percent (n = 3) were not classified; forty-six percent (n = 30) showed a focal onset and 29% (n = 19) a generalized onset; twenty-five percent (n = 16) showed a periodic pattern; focal seizures originated from the temporal areas (55%) and from the frontal areas (31%). In the control group (n = 185), focal/generalized slowing was seen in 43% (n = 80) and slowing with some spike/sharp wave activity in 2% (n = 4).

### **4. Discussion**

### **4.1 NCSE prevalence**

In the current longitudinal prospective hospital-based study, we investigated the frequency of NCSE in patients with AMS admitted to Hamad Hospital, Doha, Qatar. The prevalence of NCSE among patients with AMS was 26% at our center that is compatible with previous similar studies (prevalence = 16–37%) (**Table 6**); these researchers used a similar design, with a parallel control group; however, most were retrospective, the cEEG recording duration often shorter or not mentioned. Five other authors from MENA' s neighboring countries (mentioned in Section 1) also reported the prevalence of NCSE in patients with AMS; however, they used different study designs, and therefore, those studies cannot be compared with our study.

### **4.2 NCSE outcome**

NCSE is often associated with a poor outcome and a high mortality rate [9, 12, 13, 38]. In the current study, the mortality rate among patients with AMS and


### **Table 6.**

*Current and previous studies on NCSE prevalence and outcome.*


*Note: Variables significant at univariate analysis and having adequate numbers were used for multivariate analysis.*

### **Table 7.**

*Multivariate logistic regression for mortality in NSCE.*

NCSE was 31%, while the mortality rate among those with AMS and without NCSE was only 19%; NCSE carried a poor prognosis. Only one author reported similar outcome in NCSE and controls [9]; however death was more common in NCSE (37%) than in controls (23%). As previously reported by Young et al. [27], the length of stay and age were statistically significantly associated with mortality in the NCSE group (**Table 7**). In addition, in the current study, among patients with AMS and NCSE, head injury and stroke were associated with bad clinical outcomes with regard to recovery (**Table 8**). Also, we observed a longer hospitalization for NCSE group than that in the controls that is compatible with previous reports [13, 15].

We agree with Claassen [14] that most patients showing early NCSE EEG features (n = 13, =65%) did not achieve good outcome; we did not find any association between acute symptomatology and outcome as highlighted by Kang [39].

Patients with "periodic discharges" did not completely meet the EEG criteria for NCSE. In ICUs and cEEG monitoring units, these periodic EEG patterns are described as lying along an ictal–interictal continuum. There are convincing studies that these PDs, especially GPDs and LPDs, are strongly associated with NCSE and may be ictal [13, 15, 32, 40–45]; in fact, these EEG patterns have been found in patients with AMS,

**59**

*Nonconvulsive Status Epilepticus in Patients with Altered Mental Status Admitted to Hamad…*

**Variable OR 95% C.I. P value** Age 1.0 0.96–1.05 0.74 Length of stay 1.10 0.90–1.34 0.36 Cardiac arrest 4.22 0.64–27.9 0.14 Stroke 26.30 3.24–213 0.03 Head injury 19.5 1.30–293 0.002 *Note: Variables significant at univariate analysis and having adequate numbers were used for multivariate analysis.*

some were evolving and some responded to benzodiazepines, as shown in **Figures 1–4**. Many studies reported that PDs carry a bad prognosis, and the final outcome depends mainly on the etiology of AMS [8, 18–20, 39]; in our study, 50% of patients with PDs died; they suffered from stroke, cardiac arrest, sepsis, or head injury. However, in multivariate logistic regression analysis, we did not find a correlation between these etiologies and mortality in patients with AMS and NCSE (**Table 7**). It seems that prognosis in NCSE depends on several factors (e.g., age, etiology, level of conscious-

Finally, the outcome of refractory NCSE was very poor in our study; 9 out of 21 patients (43%) with refractory NCSE died; this is much higher than that reported in a previous study (25%) [46]. However, in that study, 17% of refractory NCSE

As reported previously, history of epilepsy/seizures could be a risk factor for

The optimal length of cEEG monitoring in critically ill ICU patients with AMS is a controversial issue in the literature. In our study, majority (66%) of NCSE cases were detected during the first 3 hours of cEEG monitoring; this detection rate reached to 90% by 48 hours of monitoring. Various required cEEG monitoring durations have been suggested in the literature; 12–24 hours [8, 12, 19, 22], 72 hours [16, 18, 47], and finally 7–10 days [23]. A recent study reported that 1/5 of patients without early EEG epileptiform features develop them during 72 hours of cEEG monitoring [25]; Claassen et al. concluded that seizures are detected only in 87% of comatose patients compared to non-comatose patients (98%) in the first 48 hours

Based on the results from our study and review of the literature, and also considering the challenges and costs associated with cEEG monitoring, we suggest that 3 days of cEEG monitoring is optimal in ICUs and in patients with AMS to detect the

To our knowledge, this is the first prospective study reporting the prevalence of NCSE in Qatar, a small country in the MENA region. This figure (26%) was in the middle range. Patients with NCSE did not do better than the controls, the result being disappointing regarding comatose NCSE. NCSE is an emerging condition requiring rapid diagnosis and rapid treatment. Regarding the duration of cEGG monitoring to diagnose the majority of NCSE cases, 3 days of cEEG monitoring could accomplish this task.

ness, etc.) and cannot be based on EEG or any one factor alone [20, 42].

*DOI: http://dx.doi.org/10.5772/intechopen.83580*

*Multivariate logistic regression for morbidity in NSCE.*

patients were in a vegetative state.

**4.3 cEEG monitoring duration**

NCSs/NCSE [12, 13, 38].

**Table 8.**

of cEEG monitoring [14].

**5. Conclusion**

majority of cases of NCSs/NCSE [14, 25].

*Nonconvulsive Status Epilepticus in Patients with Altered Mental Status Admitted to Hamad… DOI: http://dx.doi.org/10.5772/intechopen.83580*


### **Table 8.**

*Epilepsy - Advances in Diagnosis and Therapy*

**Methods Duration** 

**of EEG recording**

Retrospective ? (154) NCSE/NCSs

**Patients with AMS (n)** **Patients with NCSE (n) (%)**

Prospective 72 hs (250) 65 (26) Response to ASDs: NCSE 45/65

Prospective >24hs (170) 36 (21) Mortality 31% NCSE vs 14% in

24 (16), PEDs 45(29)

Retrospective 20mn (124) 22 (18) NCSE significant association with

Prospective 30mn (198) 74 (37) Death was more common in NCSE

**Outcome**

controls

(23%)

(69%); death: NCSE 20/65 (31%); death in controls: 35/185 (19%); complete recovery: NCSE 26/65 (40%); controls 98/185 (53%); NCSE longer hospital stay than controls p < 0.02 (**Table 5**)

NCSs/NCSE independently associated with poor outcome 20% vs 3% controls, p = 0.039

mortality, longer hospitalization

(37%) compared to controls

and poor outcome

**Author (year)**

Mesraoua et al. (2017) Current study

Laccheo et al. [38] (2015)

Kurtz et al. [12] (2014)

Bottaro et al. [13] (2007)

Privitera et al. [9] (1994)

**Table 6.**

NCSE was 31%, while the mortality rate among those with AMS and without NCSE was only 19%; NCSE carried a poor prognosis. Only one author reported similar outcome in NCSE and controls [9]; however death was more common in NCSE (37%) than in controls (23%). As previously reported by Young et al. [27], the length of stay and age were statistically significantly associated with mortality in the NCSE group (**Table 7**). In addition, in the current study, among patients with AMS and NCSE, head injury and stroke were associated with bad clinical outcomes with regard to recovery (**Table 8**). Also, we observed a longer hospitalization for NCSE group than that in the controls that is compatible with previous reports [13, 15]. We agree with Claassen [14] that most patients showing early NCSE EEG features (n = 13, =65%) did not achieve good outcome; we did not find any association

**Variable OR 95% CI P value** Age 1.16 1.0–1.34 0.05 Length of stay 2.03 1.29–3.20 0.002 Cardiac arrest 3.27 0.07–153 0.55 Stroke 35.0 0.33–3629 0.14 Head injury 30.1 0.02–56,392 0.38 *Note: Variables significant at univariate analysis and having adequate numbers were used for multivariate analysis.*

between acute symptomatology and outcome as highlighted by Kang [39].

Patients with "periodic discharges" did not completely meet the EEG criteria for NCSE. In ICUs and cEEG monitoring units, these periodic EEG patterns are described as lying along an ictal–interictal continuum. There are convincing studies that these PDs, especially GPDs and LPDs, are strongly associated with NCSE and may be ictal [13, 15, 32, 40–45]; in fact, these EEG patterns have been found in patients with AMS,

**58**

**Table 7.**

*Multivariate logistic regression for mortality in NSCE.*

*Current and previous studies on NCSE prevalence and outcome.*

*Multivariate logistic regression for morbidity in NSCE.*

some were evolving and some responded to benzodiazepines, as shown in **Figures 1–4**. Many studies reported that PDs carry a bad prognosis, and the final outcome depends mainly on the etiology of AMS [8, 18–20, 39]; in our study, 50% of patients with PDs died; they suffered from stroke, cardiac arrest, sepsis, or head injury. However, in multivariate logistic regression analysis, we did not find a correlation between these etiologies and mortality in patients with AMS and NCSE (**Table 7**). It seems that prognosis in NCSE depends on several factors (e.g., age, etiology, level of consciousness, etc.) and cannot be based on EEG or any one factor alone [20, 42].

Finally, the outcome of refractory NCSE was very poor in our study; 9 out of 21 patients (43%) with refractory NCSE died; this is much higher than that reported in a previous study (25%) [46]. However, in that study, 17% of refractory NCSE patients were in a vegetative state.

As reported previously, history of epilepsy/seizures could be a risk factor for NCSs/NCSE [12, 13, 38].

### **4.3 cEEG monitoring duration**

The optimal length of cEEG monitoring in critically ill ICU patients with AMS is a controversial issue in the literature. In our study, majority (66%) of NCSE cases were detected during the first 3 hours of cEEG monitoring; this detection rate reached to 90% by 48 hours of monitoring. Various required cEEG monitoring durations have been suggested in the literature; 12–24 hours [8, 12, 19, 22], 72 hours [16, 18, 47], and finally 7–10 days [23]. A recent study reported that 1/5 of patients without early EEG epileptiform features develop them during 72 hours of cEEG monitoring [25]; Claassen et al. concluded that seizures are detected only in 87% of comatose patients compared to non-comatose patients (98%) in the first 48 hours of cEEG monitoring [14].

Based on the results from our study and review of the literature, and also considering the challenges and costs associated with cEEG monitoring, we suggest that 3 days of cEEG monitoring is optimal in ICUs and in patients with AMS to detect the majority of cases of NCSs/NCSE [14, 25].

## **5. Conclusion**

To our knowledge, this is the first prospective study reporting the prevalence of NCSE in Qatar, a small country in the MENA region. This figure (26%) was in the middle range. Patients with NCSE did not do better than the controls, the result being disappointing regarding comatose NCSE. NCSE is an emerging condition requiring rapid diagnosis and rapid treatment. Regarding the duration of cEGG monitoring to diagnose the majority of NCSE cases, 3 days of cEEG monitoring could accomplish this task.

*Epilepsy - Advances in Diagnosis and Therapy*
