JOURNAL OF EVIDENCE BASED MEDICINE AND HEALTHCARE

Table of Contents

2019 Month : November Volume : 6 Issue : 46 Page : 2945-2949

Evaluation of the Role of Electro-Encephalography in the Early Diagnosis of Minimal Hepatic Encephalopathy in Patients with Cirrhosis of Liver

Arunabha Dasgupta1, Atul Debbarma2, Saroj Kumar Choudhury3

1. Associate Professor and I/C HOD, Department of General Medicine, Agartala Government Medical College, Agartala, Tripura.
2. Assistant Professor, Department of General Medicine, Department of General Medicine, Agartala Government Medical College, Agartala, Tripura.
3. DM Scholar, Department of Cardiology, SCB Medical College, Cuttack, Odissa.

Corresponding Author:
Dr. Arunabha Dasgupta,
Associat Professor and I/C HOD,
Departmnt of General Medicine,
#22, East Thana Road, Banamalipur,
Agartala, Tripura.
E-mail: drarunabhadasgupta@gmail.com
DOI: 10.18410/jebmh/2019/614

ABSTRACT
BACKGROUND
Hepatic encephalopathy is a serious complication of cirrhosis of liver carrying high mortality rates. Two important prognostic indicators for cirrhosis are Child-Turcotte-Pugh Class (CTP-Class) & Model for Endstage Liver disease (MELD) score. Cirrhotic subjects in advanced CTP-Class & higher MELD scores have worse prognosis. Hepatic encephalopathy is one of the causes of mortality. We wanted to evaluate the role of electroencephalography in diagnosis of minimal hepatic encephalopathy in cirrhotic individuals.

METHODS
This is a case control study where 100 cirrhotic individuals who were normal in standard clinical neurological examination procedure and without any cognitive defect were included along with 100 controls selected from patient’s attendants matching with age, sex and ethnicity. All were investigated with electroencephalography and biochemical parameters for liver function tests, INR & blood ammonia. Statistical analysis was studied to identify significant correlation existing between abnormal EEG tracing suggestive of encephalopathy with CTP-Class, MELD Scores and blood ammonia level. A p value of p<0.05 was considered significant. Calculations were done with Fisher exact test.

RESULTS
Study revealed that 33% of cirrhotic individuals having electroencephalographic changes suggestive of encephalopathy as demonstrated by grading of Parson Smith et al. EEG abnormalities were correlated to advanced CTP-Class & higher MELD scores and the results are statistically significant. Estimation of blood ammonia showed a positive correlation with higher MELD scores and individuals with abnormal EEG findings too documented high blood ammonia level. Mean blood ammonia in controls is 31.1 and cirrhotic individuals with normal EEG tracing is 39.2 and with abnormal EEG of Pattern A is 45.7 and Pattern B is 49.5. With p=0.036 significant statistical correlation was documented in cirrhotic individuals with abnormal EEG and high blood ammonia level (>45). The mean MELD score in individuals with normal EEG is 12.45 and abnormal EEG is 20.36 & p=0.006. Statistically significant association was seen between EEG changes suggestive of encephalopathy and advanced MELD scores.

CONCLUSIONS
Electroencephalography is a simple diagnostic tool of low cost and easily performed which can be employed in cirrhotic individuals for diagnosis of minimal hepatic encephalopathy for adoption of preventive approaches.

KEYWORDS
Minimal hepatic encephalopathy, cirrhosis of liver, electroencephalography, blood ammonia level, CTP-Class, MELD Score

How to cite this article

Dasgupta A, Debbarma A, Choudhury SK. Evaluation of the role of electro-encephalography in the early diagnosis of minimal hepatic encephalopathy in patients with cirrhosis of liver. J. Evid. Based Med. Healthc. 2019; 6(46), 2945-2949. DOI: 10.18410/jebmh/2019/614

BACKGROUND

Electroencephalography is the recording of electrical activity of the ionic current flows within the neurons of the brain from the scalp. It measures the voltage fluctuations due to current transmission within the neurons. In clinical context electroencephalography is the recording of brain’s spontaneous electrical activity over a period of time and the recording is performed by placing multiple electrodes on the scalp.1 Routine EEG comprises of 20-30 mins. recording during awake & resting stage using a standard array of electrodes attached over the scalp, the conventional 10-20 system. The procedure includes activation by over breathing for 3 minutes & photic stimulation.2 EEG is described in terms of rhythmic activity & is studied by means of four bands-

  1. Delta waves (<4 Hz) occur during sleep.
  2. Theta waves (4-7 Hz) occur during deep relaxation, sleep & visualization.
  3. Alpha waves (8-13 Hz) occur during calm & relaxed stage.
  4. Beta waves (13-38 Hz) occur during active thinking & problem solving.1

 

Abnormal EEG is of three types-

  1. Interictal epileptic form discharges
  2. Ictal electrographic activity
  3. Non-epileptic changes2

 

There is a qualitative classification of non-epileptic EEG changes as documented in hepatic encephalopathy described by Van der Rijt et al in 19843 and it is depicted as below-

 

Score

EEG

Description

0

Normal EEG

Well-structured in between > 8 to< 13 Hz, symmetrical & has medium amplitude. No slow activities are present. Reactive to eye opening

1

Normal Limit EEG

Unstable waves.

Suppressed alpha rhythm & replaced by diffuse beta rhythm

2

Mild signs of encephalopathy

Low frequency alpha rhythm disturbed by waves of theta range

3

Distinctive encephalopathy

Background activity in the theta range. Random appearance of high waves in delta range

4

Severe encephalopathy

Severe disorganisation without any normal waves

Diffuse asynchronous theta & delta waves with/without triphasic waves

 

Hence in encephalopathy there is a general decrease in wave frequency and increase in wave amplitude. First the alpha waves reduce & become unstable. Theta waves then predominate and are later on committed by delta waves predominance with more severe encephalopathy. The early abnormalities are found in cirrhotic patients even without overt encephalopathy.4 Parson-Smith et al first introduced the grading system of hepatic encephalopathy based on EEG characteristics.5 The term encephalopathy refers to an acute reaction of the brain to noxious agents without inflammation, or a worsening of brain function or structure compared to a previous state.6 Minimal hepatic encephalopathy (MHE) is a condition in which patients with cirrhosis of liver those who have normal mental and neurological status on standard clinical examination exhibit a number of neuropsychiatric and neurophysiological defects7 & is characterized by subtle motor and cognitive deficits impairing health related quality of life.8 MHE is present in 25-80% of cirrhotic patients without overt hepatic encephalopathy.9 Although termed minimal this state does have far reaching consequences in everyday life as there is deterioration in patient’s life style status, increased chances of accidents in any form including road traffic and to carry out professional activities that needs precision.8 MHE patients though have normal neurological examination might have problems and can be symptomatic with disturbances in sleep, memory, attention, concentration & areas of cognition.10 MHE is a marker for future development of overt hepatic encephalopathy.11 Assessment of MHE could be done with a comprehensive neurological examination which includes cognitive and motor functions evaluation.10

 

Grade of Hepatic Encephalopathy

EEG Characteristics

0

Normal regular alpha rhythm

A

Suppression of alpha rhythm, low frequency alpha rhythm, frequent replacement by faster potentials

B

Alpha rhythm unstable disturbed by random waves at 5-7 c/s

C

Random waves of 5- 6c/s in runs

D

Random waves of 5-6 c/s constant

E

2 c/s waves predominant

 

            The tests that are employed for diagnosis of MHE are-

  1. Neuropsychological tests which includes psychometric test batteries ought to examine the fields of cognition: visual perception, concentration, visual orientation, attention & memory.12 Example: number connection test; digit symbol test; circle dotting.13
  2. Neurophysiological tests –
  3. Simple electroencephalogram3
  4. Evoked potentials: auditory; visual & somatosensory14
  • P30015
  1. Computerized psychometric test: critical flicker frequency16
  2. Magnetic resonance spectroscopy.17

 

Child-Turcotte- Pugh (CTP) and MELD scores have been used widely for assessment of prognosis in liver cirrhosis.18 Studies report mortality rates associated with different class of CTP documenting higher mortality rates with class B & C in comparison to class A indicating poorer prognosis with class B & C. Meld score is objective ranges from 6 to 40 points and is validated by various studies. Patients with higher scores are having poorer prognosis and it is generally accepted that MELD score <15 have a better survival rate.19

The present study was conceptualized with an aim to identify EEG abnormalities present in cases of cirrhotic patients classified by CTP-Class & MELD Scoring who were otherwise normal neurologically on clinical evaluation and with an aim of early adoption of therapeutic preventive measures on those cases with EEG abnormalities; so that development of overt hepatic encephalopathy can be dealt with.

 

METHODS

Cases were selected from liver clinic and ward that were confirmed cases of cirrhosis of liver, confirmation done by clinical examination & ultrasonography (coarsened echo texture of liver, shrunken size, presence of regenerative nodules in liver along with splenomegaly and ascites). The patients were screened clinically for presence of overt hepatic encephalopathy by detailed history and neurological examination. Only those cases without any evidence of overt hepatic encephalopathy and having a normal neurological examination were selected by systemic random sampling as cases and were subjected to electroencephalography. Serum samples were obtained from the cases for biochemical tests and were analysed for blood sugar, haemogram, liver function tests, kidney function tests and serum electrolytes: Na+, K+ & Ca+. INR and blood ammonia were also evaluated in all the cases. EEG was performed in all cases using standardized techniques. 21 electrodes were used attaching over the scalp at conventional positions according to the international 10-20 system. Electrode impedance was kept lower than 5k. EEG was recorded for 20 minutes with eyes closed in a state of relaxed wakefulness. All controls were also investigated accordingly with liver function tests, INR & blood ammonia level. The controls underwent electroencephalography using identical techniques. Results obtained are analysed & statistical associations are documented thereafter.

Statistical analysis was performed using the Statistical Package for the Social Science (SPSS) version 16 IBM Corporation. A p value of <0.05 was considered statistically significant.

 

RESULTS

There were 100 cases of patients of cirrhosis of liver who were having normal neurological examination clinically and were simultaneously evaluated for presence of minimal hepatic encephalopathy. The cases were evaluated by classifying them into CTP-Class, MELD scoring, and blood ammonia levels with INR. Electroencephalography was performed and an attempt was made to evaluate if any significant statistical co-relation exists in between changes in electroencephalogram with blood ammonia level, CTP-Class & MELD scoring.

The maximum percentage of patients belonged to 51-70 yrs. (50%) and the youngest patient was of 21 yrs. old and the eldest was 84 yrs. old. The mean age of patients having cirrhosis was 58.96±14.2 yrs. and there was a male preponderance- male 56% and females 44%. Child-Turcotte-Pugh (CTP) Score was calculated for each patient and the results showed that 47% of the patients belonged to CTP-A Class and 28% were in CTP-B class and 25% in CTP-C class.

 

 

CTP Class

Number of Patients

A

47

B

28

C

25

Table 1. Distribution of Cirrhotic Cases with CTP-Class

 

The calculation of Model for End Stage Liver Disease (MELD) Score among the 100 patients revealed the following distribution-

 

MELD Score

Number of Patients

6-10

29

11-15

26

16-20

24

21-25

13

26-30

6

31-35

2

Table 2. Distribution of Cirrhotic Cases with MELD Scores

 

The results showed that 29% of patients scored MELD score of 6-10; followed by 26% of score 11-15 & 24% scored 16-20.13% of cases had MELD score of 21-25. The frequency of patients in higher scores dropped after that & we have no patients with score above 35. The classification of hepatic encephalopathy based on EEG findings was done by Parson-Smith et al5 and our study revealed that 67% of the patients had a normal EEG & the rest 33% had abnormal findings in EEG.

 

Hepatic Encephalopathy Grade (Parson-Smith Grading)

EEG Status

Number of Patients

p

O

Normal

67

 

< 0.0001

A

Abnormal

17

B

Abnormal

16

Table 3. Grading of Hepatic Encephalopathy with EEG Changes

 

Out of the 100 controls only 6 subjects had abnormal EEG findings and statistical correlation revealed significant association of abnormal EEG recordings in patients of cirrhosis of liver who were otherwise normal on clinical neurological evaluation (p<0.0001). The distribution of blood ammonia level among the patients showed the following result-

 

Blood Ammonia Level in mcg/dl

Number of Patients

11-20

8

21-30

13

31-40

12

41-50

19

51-60

17

61-70

22

71-80

9

Table 4. Distribution of Blood Ammonia Level among the Cases

 

Most of the literatures opine that in adults the reference range for normal ammonia level is 10-80 mcg/dl20 & in this study all cases had blood ammonia level within the reference range. The mean blood ammonia level in cases was 44.03±12.2 & in controls was 31±13.4 and estimation of p value showed this result being statistically significant and blood ammonia levels were significantly different in both the groups and they are higher in cirrhotic individuals.

 

Blood Ammonia Level

Cases (n=100)

Controls (n=100)

p

44.03±12.2

31.1±13.4

<0.00001

Table 5. Statistical Analysis of Blood Ammonia Levels in Cases & Controls

 

EEG Changes

Blood Ammonia Level (mcg/dl)

 

Frequency

Mean

S.D.

p

Normal

Pattern O

67

39.2

11.1

0.036

Abnormal

Pattern A

17

45.7

8.6

Pattern B

16

49.5

10.3

Table 6. Statistical Analysis of EEG Changes with Estimation

of Blood Ammonia in Cirrhotics

 

Of the 33 case-subjects who had abnormal EEG findings an attempt was made to identify any correlation existing between blood ammonia level and the study revealed: in abnormal EEG changes of Pattern A the mean blood ammonia value was 45.7 whereas in Pattern B it was 49.5 and when compared with cases who had normal EEG tracing (Pattern O) the value for blood ammonia was 39.2. So, in abnormal EEG tracing the value for blood ammonia was higher and 2 tailed unpaired t- test showed a p= 0.036 which is statistically significant. The study for correlating abnormal EEG findings with CTP Class (A, B & C) showed the following distribution-

 

CTP Class

EEG Changes

 

p value

Normal EEG

Abnormal EEG

A

41

6

 

p= 0.000012

B

18

10

C

8

17

Table 7. EEG Changes in CTP-Class

 

This statistically significant finding p= 0.000012, revealed cases in CTP Class B & C were having more number of cases with abnormal EEG findings as against cases of CTP Class A where more subjects had normal EEG tracing. The correlation of EEG tracings and MELD Scores showed the following status-

 

EEG Changes

MELD Score

Frequency

Mean

S.D.

p value

Normal

Pattern O

67

12.45

5.08

 

p=0.006

Abnormal

Pattern A

17

18.47

3.77

Pattern B

16

22.38

4.12

Table 8. EEG Changes with MELD Scoring

 

The mean MELD score among cases with normal EEG finding was 12.45 & mean MELD score among abnormal EEG tracing was 20.36 and it was significantly higher among cases with abnormal EEG findings (p= 0.006).

DISCUSSION

The study was conducted with a view to observe electroencephalographic changes present in 100 cirrhotic subjects sampled from liver clinic of our hospital who have been evaluated by CTP-Class & MELD scoring and did not had any evidences of overt hepatic encephalopathy and neither any neurological or psychiatric ailments which influences the cognitive functions. The observation of correlation of CTP-Class with MELD scoring showed a positive relationship. CTP-Class B & C has higher MELD scores and hence both having poor prognosis. The mean MELD score of cases in CTP-Class A is 10.36±2.95 much lower than the MELD score of CTP-Class B which is 15.96±3.16 whereas for CTP-Class C the score is much higher 22.88±4.30 Estimation of blood ammonia level also revealed significant statistical difference (p<0.00001) in between cirrhotic groups and controls with a mean value of blood ammonia of 44.03±12.2 in cases and 31.1±13.4 in controls. Along with there is a positive correlation of blood ammonia with MELD scores (r = +0.09) which signifies that as the MELD scores increases the mean blood ammonia level too increases. While studying the correlation of blood ammonia with EEG findings a statistically significant correlation was documented (p=0.036) showing that cirrhotic subjects with higher level of blood ammonia (mean value of blood ammonia >47.8±10.1) have EEG changes suggestive of encephalopathy by Parson-Smith grading system.

The study of EEG changes with CTP-Class demonstrated in CTP- Class- A 6 subjects had EEG changes suggestive of encephalopathy and in CTP-Class B 10 subjects and in CTP-Class C 17 subjects have demonstrated EEG abnormalities. The Fisher Exact test showed p=0.000012 implying a highly significant result that higher the CTP grades more are the chances of developing EEG changes suggestive of encephalopathy in cirrhotics. While exploring the correlation of MELD scores & EEG changes it was demonstrated that higher the MELD score more are the chances of EEG changes. The mean MELD scores of cases with normal EEG is 12.45±5.08 as against those with abnormal EEG was 20.36±4.5. And this result is statistically significant (p=0.006). Of the 33 subjects who demonstrated abnormal EEG 17 showed changes of Pattern A & rest 16 revealed changes of Pattern B type as per Parson-Smith grading. This result is also statistically significant (p<0.0001). Electroencephalographic changes suggestive of encephalopathy are present in cirrhotic subjects with higher blood ammonia levels and advanced grade of CTP-Class & higher MELD scores even though they may not demonstrate neurological deficits on clinical examination and history.

CONCLUSIONS

The study showed statistically significant association of EEG changes suggestive of encephalopathy with advanced CTP-Class of B & C and higher level of MELD scoring above 15. EEG changes were also documented with higher blood ammonia level which was also associated with advanced CTP-Class and MELD score. All results are statistically significant (p<0.05). So, electroencephalography can be used as a diagnostic tool to identify encephalopathic changes in cirrhotic population even though the subjects might not demonstrate symptoms suggestive of overt encephalopathy and early therapeutic approaches can be adopted for prevention.

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