Online ISSN : 1687-8329

    




Quick Search 
 
Author  
Year    
Title  
Vol:  

 
 
July2014 Vol.51 Issue:      3 (Supp.) Table of Contents
Full Text
PDF


Value of Continuous EEG Monitoring, Emergent IV Benzodiazepines Administration in the Diagnosis of Nonconvulsive Status Epilepticus in Adults

Ehab Shaker1, Husam Salah1, Heba Raafat2

Departments of Neurology1, Clinical Neurophysiology Unit2, Cairo University; Egypt



ABSTRACT

Background: Nonconvulsive Status Epilepticus (NCSE) is much more common than generally appreciated. It is certainly underdiagnosed. NCSE may be one of the most frequently missed diagnoses in patients with altered neurologic function. The diagnosis of NCSE is important to make because NCSE impairs the patient’s health significantly and it is in most cases a treatable and completely reversible condition. Objective: The aim of the present study is to propose unified diagnostic criteria of NCSE in adults including a combination of three: Clinical suspicion, continuous EEG (cEEG) monitoring and emergent I.V benzodiazepines administration during cEEG monitoring. Methods: The study was conducted on 15 adult patients with pre-existing controlled epileptic syndrome and others with altered conscious level without any known cause. Thorough history taking, neurological examination, cEEG monitoring, and emergent IV benzodiazepines administration during cEEG were done to the patients. Results: Frequent and continuous generalized spike-and wave discharges were found in 46.66% of previously well-controlled epileptic patients, frequent and continuous focal discharges were found in 20% of previously known epileptic patients, frequent continuous generalized discharges without a prior history of epileptic syndrome were found in 13.33%, and periodic complexes were recorded in 20% of patients with coma. Upon emergent IV administration of Benzodiazepines during cEEG monitoring, all of them showed immediate EEG improvement and sometimes with clinical improvement (20%). Conclusion: This study concluded that cEEG monitoring and the simultaneous improvement of the cEEG criteria with or without clinical improvement after emergent IV administration of Benzodiazepines added unified diagnostic criteria of clinically suspected NCSE in adults. [Egypt J Neurol Psychiat Neurosurg.  2014; 51(3): 337-344]

Key Words:  NCSE; ICU; coma; cEEG; IV benzodiazepines.

Correspondence to Heba Raafat, Clinical Neurophysiology Unit, Faculty of Medicine, Cairo University; Egypt. Email: raafatheba@kasralainy.edu.eg

 






INTRODUCTION

 

The diagnosis of nonconvulsive status epilepticus is challenging as it is commonly underdiagnosed and missed although it is very common among patients with disturbed neurologic function. It may be mistaken for many other conditions as it causes disturbance in alertness and cognitive function up to confusion and in some cases coma, but fortunately, it is usually a treatable and reversible illness especially if not associated with severe encephalopathy.1

Nonconvulsive status epilepticus may occur up to 50% in patients with coma or convulsive status epilepticus. It also occurs in about 8-37% of the general ICU population2

 

Nonconvulsive status epilepticus should be suspected in patients with generalized tonic-clonic seizures with prolonged postictal period, unexplained stupor or confusion in the elderly especially those taking neuroleptic medication, and finally in patients with altered mental status in whom no other cause can explain this situation3

Absence and complex partial status epilepticus are characterized by prolonged confusion varying from clouding of consciousness to stupor. In classical cases coma is unlikely to occur. In cases of in complex partial status epilepticus, this disturbed mental function or altertness and confusion is termed “epileptic twilight state”. Absence status epilepticus can be associated with minimal motor manifestations in the form of intermittent blinking or myoclonus of the face and lips lasting for hours to days while complex partial status epilepticus can be associated by motor automatisms as aversion of the head and eyes and often consists of prolonged or repetitive complex partial seizures. However, there is a clear overlapping of syndromes especially when nonconvulsive status epilepticus arises after a convulsive seizure with minimal motor manifestations and no obvious focal automatism4

Confused or comatose patients with continuous or frequent rhythmic epileptiform discharges on the EEG should be involved in this type of status epilepticus1

The mortality rate in those comatose patients can exceed 30% if the seizure duration is greater than 60 minutes5.

 Nonconvulsive status epilepticus typically occurs following supposedly well-controlled seizures, but with persistent disturbance in alertrness1

Many authors tried to define electroencephalography (EEG) characteristics of NCSE without a universally accepted definition6,7.

Finally, criteria for diagnosis of NCSE should include all of the following three: Clinically suspected NCSE, continuous or frequent EEG discharges and immediate EEG improvement upon emergent I.V benzodiazepines administration while cEEG recording with or without clinical improvement1

 

SUBJECTS AND METHODS

 

        This study included 15 adult patients. It included 11 females and 4 males. These cases were recruited from the Neurology ICU of Kasr Al-Aini, Manial, and Kasr Al-Aini New Teaching Hospitals.

 

Inclusion Criteria:

-        Adult patients with pre-existing epilepsy and controlled seizures but with persistent neurological dysfunction despite adequate treatment

-        Patients with altered consciousness and behavior without any obvious cause

-        Adult patients with no prior epilepsy “de novo status epilepticus” with history of drug withdrawal.

 

Exclusion Criteria:

-        Patients with previously diagnosed metabolic disturbances: Electrolyte abnormalities, hypoglycemia, renal failure, sepsis

-        Patients with central nervous system infection: meningitis, encephalitis

-        Stroke: Ischemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage

-        Head trauma with or without subdural hematoma

-              Non-compliance with AEDs

-              Hypertensive encephalopathy

-              Children and adolescents with suspected NCS.

 

The diagnostic work up included:

-              Rich history taking from one of the relatives

-              Thorough general and neurological examination

-              Finger stick glucose test

-              CT brain scan

-              Laboratory tests:

   Blood glucose level

   Complete blood picture

   Basic metabolic panel

   Calcium (total and ionized), magnesium level

-              cEEG Monitoring:

Portable digital 32 channel-EEG machine was used with special settings for EEG machine in the ICU

  Sensitivity: no less than 2 µV/mm

  Low frequency cut off : no higher than 2 Hz

  High frequency cut off: no lower than 50 Hz

  60 Hz notch filter to reduce interference

  Interelectrode impedance: below 10.000 but above 1.000 ohms

  Duration of recording: not less than 1 hour unless the appearance of continuous discharges which disappeared upon I.V Midazolam administration

  Timing:  cEEG was performed within few hours of suspected NCSE

-        Emergent I.V. Benzodiazepines Initial Therapy:

I.V Benzodiazepines (Midazolam) was administrated immediately upon the appearance of electroencephalographic criteria of NCSE with a dose of 0.15 mg/kg IV up to 10 mg per dose, which may be repeated in 5 minutes. Midazolam was sometimes used with an interrupted dose of 0.5 mg/1 min till a maximum dose of 8 mg or electrographic improvement with or without clinical improvement.

 

RESULTS

 

Ten cases (66.67%) out of the 15 studied patients had a previous history of primary epilepsy, two patients (13.33%) had history of drug withdrawal. Typical absence status epilepticus was clinically suspected in eight cases (53.33%), complex partial status epilepticus in two cases (13.33%), late adulthood denovo nonconvulsive status epilepticus in two cases (13.33%) and coma with epileptic EEG changes in three cases (20%) as shown in Table (1).

The clinical features of absence status epilepticus were in the form of confusion found in all eight cases (53.33%), minimal motor manifestations in the form of blinking or occasional myoclonus of the face and lips in 6 cases (46.15%), prior existing seizures in all 8 cases (53.33%). All patients suspected to have nonconvulsive status epilepticus had the attack lasting for days (Table 2).

The clinical features of complex partial status epilepticus were in the form of confusion to unresponsiveness “epileptic twilight state” with fluctuating mental status found in both cases with complex partial status epilepticus (100%). They also showed recurrent focal seizures in the form of automatism. Both of them had a prior history of epilepsy (Table 3).

The clear-cut criteria of EEG characteristics in the studies patients were in the form of frequent or continuous generalized spike-and wave discharges observed in seven cases (46.66%), frequent or continuous focal discharges observed in three cases (20%) One patient who was clinically suspected to have absence status epilepticus showed continuous focal temporal epileptiform discharges upon cEEG monitoring which therefore shifted the diagnosis to complex partial status epilepticus. These generalized and focal spike-wave discharges occurred in patients with prior history of epilepsy. Frequent or continuous generalized spike-and wave discharges without a prior history of epileptic syndrome occurred in 2 cases (13.33%), and finally periodic discharges in patients with coma were found in 3 cases (20%) as shown in Table (4).

The EEG features in NCSE were shown in Table (5) which included spike-slow complexes in 12 cases (80%) and periodic discharges in three cases (20%). Their location was generalized in 12 cases (80%) and lateralized in three cases (20%). Frequency of the discharges were > 2.5 Hz in 12 cases (80%) and < 2.5 Hz in three cases (20%). All EEG changes were spontaneously induced.

All studied patients showed immediate EEG improvement (Table 6.) upon emergent I.V. Midazolam administration, while only three cases (20%) showed immediate clinical improvement together with the EEG improvement.

The sensitivity of cEEG monitoring in clinically suspected NCSE in this study was 100%, while the sensitivity of I.V. benzodiazepines as recording EEG improvement was 100% and as regarding clinical improvement alone was 20%.

Improvement of the EEG picture of NCSE was in the form of gradual disappearance of the continuous or frequent EEG discharges and return to normal background observed in all studied patients, as shown in Table (7).


 

Table 1. Types of  NCSE without encephalopathy.

 

 

Typical Absence Status Epilepticus

N(8)

Complex Partial Status Epilepticus

N (2)

Late Adult

de novo

N(2)

Boundary syndrome

(coma with epileptic EEG changes)

N(3)

Percentage

53.33%

13.33%

13.33%

20%

N=number 

   

Table 2. Clinical features in Absence status Epilepticus N(8).

 

 

Confusion

N(8)

Blinking or occasional myoclonus

N(6)

Prior Absence, myoclonic or convulsive seizures

N(8)

Lasting days

N(8)

Percentage

53.33%

46.15%

53.33%

53.33%

N=number

 

Table 3. Clinical features in complex partial status epilepticus N (2).

 

 

Confusion to unresponsiveness "twilight state" with fluctuating mental status

N(2)

Recurrent complex partial seizures

N(2)

Prior Epilepsy

 

N(2)

Percentage

100%

100%

100%

N=number

 

Table 4. Clear-cut criteria of EEG picture in NCSE (According to Drislane, 2000).

 

 

Frequent or continuous generalized spike – and wave discharges

N(7)

Frequent or continuous focal discharges

N(3)

Frequent or continuous generalized spike- and wave discharges without a prior history of epileptic syndrome

N(2)

Periodic discharges in patients with coma

N(3)

Percentage

46.66%

20%

13.33%

20%

N=number

Table 5. EEG Features in NCSE.

 

Name of the Patten

·                  Spike – slow wave complexes

·                  Periodic discharges

 

N(12)

N(3)

 

80%

20%

Location

·                  Generalized

·                  Lateralized

 

N(12)

N(3)

 

80%

20%

Time – related features

·                  Frequency > 2.5Hz

·                  Frequency < 2.5 Hz

 

N(12)

N(3)

 

80%

20%

Modulation

·                  Spontaneous

·                  Stimulus – induced

 

N(15)

N (0)

 

100%

0%

 

Table 6. Immediate improvement after emergent I.V Benzodiazepines administration.

 

              

N(15)

Percentage

Improvement of EEG picture

N(15)

100%

Improvement of both clinical and EEG picture

N(3)

20%

N=number

 

Table 7. Forms of improvement of EEG picture in NCSE.

 

 

N(15)

Percentage

Return to normal background

N(15)

100%

Gradual disappearance of continuous or frequent EEG discharges

N(15)

100%

N=number

 

 

 

Fig (1a)

 

 

Fig (1b)

 

Fig (1c)

 

Figure 1. cEEG  monitoring example of  absence status epilepticus in a patient known of be epileptic with apparently well controlled seizures showing continuous generalized 3 Hz frequency discharges (a,b) which disappeared totally after 2-3 minutes of emergent I.V. administration of Midazolam (c).

 

Fig. (2a)

 

Fig. (2b)

 

Figure 2. cEEG monitoring example of complex partial status epilepticus in a patient known to be epileptic with previously well controlled complex partial seizures showing continuous focal 3 Hz frequency discharges (a) which was abolished significantly after 2 minutes of emergent I.V. administration of Midazolam (b).

 

 


DISCUSSION

 

The diagnosis of nonconvulsive status epilepticus (NCSE) should be much more appreciated as it very common among patients with altered neurologic function and often missed in diagnosis. The diagnosis of NCSE is crucial to make because NCSE impairs the patient’s health significantly and increases the mortality rate among ICU patients, while it is often a treatable and completely reversible condition when diagnosed properly1.

Many authors tried to define the electroencephalography (EEG) characteristics of NCSE without finding a universally accepted definition6,7.

We conducted this study to propose unified diagnostic criteria of NCSE in adults including a combination of three: Clinical suspicion, cEEG monitoring, and emergent I.V benzodiazepines administration during cEEG monitoring.

The clinical features of absence status epilepticus were in the form of confusion (53.33%), blinking or occasional myoclonus (46.15%), prior existing seizures (53.33%). All patients had nonconvulsive status epilepticus lasting for days.

This agrees with the study of Drsilane1 that showed almost the same clinical features of absence status epilepticus

 

The clinical features of complex partial status epilepticus were in the form of confusion to unresponsiveness “twilight state” with fluctuating mental status found in both cases clinically suspected to be complex partial status epilepticus.

They also showed recurrent complex partial seizures in the form of automatism. Both of them had a prior history of epilepsy, which agrees with the clinical features of complex partial status epilepticus studied by Drislane1

The clear-cut criteria of EEG characteristics in the studied patients were in the form of frequent or continuous generalized spike-and wave discharges (46.66%), frequent or continuous focal discharges (20%), frequent or continuous generalized spike-and wave discharges without a prior history of epileptic syndrome (13.33%), and finally periodic discharges in patients with coma (20%).

This agrees with the unified EEG terminology and criteria for nonconvulsive status epilepticus stated by Beniczky et al.7

Snodgrass and colleagues8 considered periodic discharges to be a risk factor for more seizures and the “terminal phase of status epilepticus” which was proven by the poor outcome observed in our three studied patients with periodic discharges. These patients were presented with coma, but unfortunately EEG monitoring wasn’t done before 60 minutes of clinical suspicion of nonconvulsive status epilepticus and the outcome was poor supported by Chang and Shinnar5 reporting that the mortality rate can exceed 30% in comatose patients if the seizure persists for more than 60 minutes and wasn’t managed emergently5

The continuous spike-slow wave discharges were generalized (absence status epilepticus) in 80% of cases and lateralized (complex partial status epilepticus) in 20% of cases. Frequency of the discharges were > 2.5 Hz in 13 cases (80%) and < 2.5 Hz (20%). All continuous EEG discharges were spontaneously induced.

This agrees with the study performed by Frank1 that stated that absence status epilepticus are much more common than complex partial status epilepticus.

The fact that complex partial seizures are far more common than absence seizures in overall adult life lead many authors to the conclusion that there is overlapping of both NCSE syndromes and that these two types cannot be differentiated on clinical basis only and therefore confused the classification of NCSE when classified on clinical or cEEG monitoring alone4

This was applied to one of our studied patients who was formerly suspected to be absence status epilepticus on clinical background while cEEG monitoring proved it to be complex partial status epilepticus.

Moreover, many NCSE patients with continuous generalized EEG discharges had focal discharges on interictal EEGs8,9.

Immediate EEG improvement upon emergent I.V. Midazolam administration was observed in all studied patients, while only 20% of cases showed immediate clinical improvement in addition to the EEG improvement.

This agrees with Drislane1, who stated EEG improvement in all his studied cases after emergent I.V. Benzodiazepines administration.

Improvement of the EEG picture of NCSE was in the form of gradual disappearance of the continuous or frequent EEG discharges and return to normal background matching with the study of Drislane1

Sensitivity of cEEG monitoring of clinically suspected NCSE when combined with emergent IV benzodiazepines-immediate EEG improvement was 100%.

In conclusion, the diagnosis of NCSE should include clinical suspection of NCSE, cEEG monitoring and emergent I.V. benzodiazepines administration during CEEG monitoring whenever the diagnosis is suspected as these diagnostic criteria are critical for the proper management and reduction of the mortality rate of NCSE patients among ICU patients.

 

[Disclosure: Authors report no conflict of interest]

 

REFERENCES

 

1.        Drislane FW. Presentation, Evaluation and Treatment of nonconvulsive status epilepticus Epilepsy Behav. 2000 Oct;1(5):301-14.

2.        Shah AM, Vashi A, Jagoda A. Review article: convulsive and nonconvulsive status epilepticus: an emergency medicine perspective. Emerg Med Australas. 2009 Oct; 21(5): 352-66.

3.        Meierkord H, Holtkamp M. Nonconvulsive status epilepticus in adults: clinical forms and treatment. Lancet Neurol. 2007 Apr; 6(4): 329-39.

4.        Tomson T, Lindbom U, Nilsson BY. Nonconvulsive status epilepticus in adults: thirty-two consecutive patients from a general hospital population. Epilepsia. 1992 Sep-Oct;33(5):829-35.

5.        Chang AK, Shinnar S. Nonconvulsive status epilepticus. Emerg Med Clin North Am. 2011 Feb; 29(1):65-72.

6.        Sutter R, Kaplan PW. Electroencephalopgraphic criteria for nonconvulsive status epilepticus: synopsis and comprehensive survey. Epilepsia. 2012; 53 (3): 1-51.

7.        Beniczky S, Hirsch LJ, Kaplan PW, Pressler R, Bauer G, Aurlien H et al. Unified EEG terminology and criteria for nonconvulsive status epilepticus. Epilepsia. 2013; 54 (6): 28-9

8.        Snodgrass SM, Tsuburaya K, Ajmone-Marsan C. Clinical significance of periodic lateralized epileptiform discharges: relationship with status epilepticus. J Clin Neurophysiol. 1989 Apr; 6(2):159-72.

9.        Granner MA, Lee SI. Nonconvulsive status epilepticus. EEG analysis in a large series. Epilepsia. 1994 Jan-Feb;35(1):42-7

10.     Bauer G, Trinka E. Nonconvulsive status epilepticus and coma. Epilepsia. 2010 Feb; 51(2):177-90.

11.     Kaplan PW. EEG criteria for nonconvulsive status epilepticus. Epilepsia 2007; 48(8):39-41.


 

 

الملخص العربى

 

قيمة رسم المخ المستمر والبنزودايازبين الوريدي مدخل لتشخيص

الحالة الصرعية اللااختلاجية في البالغين

 

الخلفية: الحالة الصرعية اللااختلاجية أكثر شيوعا مما هو مقدر إذ إنها تفتقر إلى التشخيص وأنها تمثل أكثر التشخيصات غيابا في المرضي الذين يعانون من تغيير في وظائفهم العصبية. تشخيص الحالة الصرعية اللااختلاجية له أهمية إذ انه يؤثر سلبا على صحة المريض فضلا عن انه يمكن علاجه. الهدف: هو اقتراح معايير مراقبة موحدة لرسم المخ المستمر للحالة الصرعية اللااختلاجية يتم فيها المزج بين ثلاثة عوامل: الشك الاكلينيكى، التخطيط المستمر للمخ وإعطاء عقار البنزودايازبين بالوريد أثناء التخطيط. الطرق: تم إجراء الدراسة على ١٥ مريض منهم من يعاني من مرض الصرع المستجيب على الأدوية ومنهم من يعاني من اضطراب في درجة الوعي بدون سبب ظاهر. تم عمل الآتي لجميع المرضي: تاريخ مرضي كامل كشف سريري تخطيط مخ مستمر وإعطاء عقار البنزودايازبين بالوريد أثناء التخطيط. النتائج: شوكات وموجات حادة معممة متكررة ومستمرة تم العثور عليها في ٤٦٫٦٦٪ من مرضي الصرع المستجيبين سابقا على العلاج وتم العثور على شوكات وموجات حادة بؤرية متكررة ومستمرة فى ٢٠٪ من مرضي الصرع، كما تم العثور على تفريغات مستمرة ومتكررة في المرضي الذين لا يعانون من تاريخ سابق للصرع وذالك في ١٣٫٣٣٪ ومجموعات دورية تم تسجيلها في٢٠٪ من مرضي الغيبوبة وبعد إعطاء عقار البنزودايازبين تحسن التخطيط فيهم جميعا وصاحبه تحسن إكلينيكي في ٢٠٪. الاستنتاج: هذه الدراسة توضح ان تخطيط المخ المستمر وتزامن تحسنه سواء صاحبه تحسن إكلينيكي أو لم يصاحبه بعد إعطاء عقار البنزودايازبين الوريدي أضاف معيار تشخيصي للاشتباه الإكلينيكي في الحالة الصرعية اللااختلاجية في البالغين.

 



2008 � Copyright The Egyptian Journal of Neurology,
Psychiatry and Neurosurgery. All rights reserved.

Powered By DOT IT