EFFECTS OF HYPERVENTILATION ON ELECTROENCEPHALOGRAM OF NORMAL AND EPILEPTIC PATIENTS.

 Srinivasulu Naidu.S*, Shashikala K.T* , Rajeev Sharma**,  Srinivasa R***                                           

* Assistant professor of Physiology,Bangalore Medical College & Research Institute,Bangalore.

 Corresponding Author –  

Dr.Srinivasulu Naidu. S,No 37,5th B Cross,Sarakki Main Road,

J.P.Nagar I st Phase,Bangalore 560078,

Karnataka,INDIA.

Mobile 9880656516,

E-Mail(srnvslnaidu@yahoo.co.in)

ABSTRACT

Purpose of the study

Voluntary hyperventilation (HV) has been widely used in clinical EEG laboratories as “activation method” to enhance preexisting abnormalities and / or induce abnormal findings in an otherwise normal electroencephalogram(EEG).The present work was done to,

a. compare  the incidence of epileptiform activity during hyperventilation test on the EEGs of  normal and epilepitics.

b. Quantification of Changes in different seizure categories like

            (a) Absent, (b) Focal and (c) Generalized.

Methods: EEGs were recorded using hyperventilation test as activation procedures in 50 patients, who were proven cases of epilepsy with different seizure categories and compared with 50 age and sex matched normal subjects. Effects of hyperventilation test on EEG were recorded and changes were analyzed statistically.

Results: Hyperventilation test had a moderately significance result in activation of Interictal epileptiform discharges (IEDs) (P=0.012).

Effect of activation was seen maximally in patients of generalized seizures especially in GTCS and Absence seizures (40%).

Interpretation and Conclusion: This work suggests that Hyperventilation test provoke epileptiform changes in EEGs Of epileptic patients and hence increase the yield of EEG recordings.

Keywords:. Electroencephalogram, Hyperventilation, Interictal Epileptiform discharges.

 

INTRODUCTION

The EEG is the most common neurodiagnostic test performed to evaluate patients with suspected seizures and for seizure management.

EEG provides a continuous measure of cortical function with excellent time resolution and is relatively inexpensive,noninvasive and safe as compared to newer brain imaging techniques.

Several activation techniques like hyperventilation, intermittent photic stimulation, sleep, and sleep deprivation have been used in clinical EEG laboratories to enhance preexisting abnormalities and / or induce abnormal findings in an otherwise normal EEGs . However, despite being utilized in routine clinical EEGs for decades, a number of differing views on the usefulness and indications for these procedures exist.(1)(2)

There has been considerable variability in the literature reported regarding EEG abnormalities in normal adult and epileptics using “hyperventilation test”. Therefore, the present work was undertaken by using “hyperventilation test” to,

a. compare the incidence of epileptiform activity during hyperventilation test on the EEGs of  normal and epilepitics.

b. Quantification of Changes in different seizure categories like

(a) Absent,  (b) Focal and (c) Generalized.

 METHODS:

The sample used in this study consisted of 50 epileptic patients and 50 age matched normal subjects.Our study was a comparative study in which 50 Rt handed proven epileptic patients between the age group of 10-30 yrs, attending outpatient departments at M. S. Ramaiah Medical and Teaching Hospital were studied and further compared with age matched normal healthy subjects from the general population.

Ethical clearance was obtained from the M. S. Ramaiah Medical College ethical committee for human research to conduct the study.Patients with a history of Neurological diseases, Head injury ,Migraine ,Drug abuse, Severe cardiopulmonary disease, Left handed Men, Uncontrolled hypertension,Sickle cell anemia were excluded from the study..

Data was collected from 50 males with known history of seizures and  proven cases were taken as epileptic subjects who satisfied the inclusion and exclusion criteria were recruited from M.S. Ramaiah Medical and Teaching Hospital.

In epileptics,25 patients had partial seizures and 25 patients had generalized seizures.

Age and sex matched normal volunteers without a history of seizures were taken from the general population. The study extended over a period of two years.

PROCEDURES AND EQUIPMENT

EEGs were recorded on a 21-channel EEG Nihon Kohden Neurofax Electroencephalograph EEG-1100.

EEGs were recorded from 21scalp sites based on the international 10-20 system (1), using silver/silver chloride electrodes with a ground electrode at the forehead, and use of referential, longitudinal bipolar and transverse bipolar montages.

It was explained that hyperventilation (“deep breathing test”) might bring on attacks. The consent form was signed at this stage.

Before the commencement of HV, the technologist explained and demonstrated the rate and depth of HV effort and asked the patient to hyperventilate continuously with the eyes closed. HV was performed in the supine position for 5 minutes.

Hyperventilation protocol (1) includes for 5 minutes of maximum effort from the subject. EEG activity will be recorded in the baseline condition for 1 minute with eyes closed condition and for 5 minutes during HV when they are asked to breath deeply with eyes closed.

EEG findings during HV and baseline condition were  tabulated as showing

a) No changes.

b) Clinical seizures that included ictal EEG patterns.

c) An increase inter ictal epileptiform discharges(IED’s).

All EEGs were interpreted by neurolist.

Difference in the 2 groups will be statistically analysed using

1) Analysis of variance          2) Chi-Square chart.

Investigations and interventions conducted on patients :

Study involved non-invasive EEG recordings for both cases and controls in the department of neurology  as described earlier with no financial liability on them.

 RESULTS AND ANALYSIS

This  Case control study consisted  of 50 normal and 50 epileptic patients were  undertaken to study and compare the incidence of epileptiform activity seen in EEG of normal, and epileptic patients during hyperventilation, Quantification of Changes in different seizure categories like (a) Absent,  (b) Focal.

Hyperventilation test had a moderately significance result in activation of IEDs. P=0.012. (Table-1)

In our selected series of 50 epileptic  patients with different categories,

epileptiform EEG changes was observed  in 24% of the epileptic patients during HV. (Table-2, Figure-1,Figure-2).

Hyperventilation could not produce any epileptiform changes or clinical seizures  in the EEGs of normal controls.

A clinical seizure occurred  during HV only in 1 patient with absence seizures.( Figure-2)

IEDs, in turn, were increased in 24% and 1% of the patients with generalized and partial epilepsies, respectively. (Table-1, Figure-1).

Effect of activation was seen maximally in patients of generalized seizures especially in GTCS and Absence seizures(40%).(Table-2, Figure-2)

Statistical Methods: Chi-square and Fisher exact test have been used to test the significance of changes in IEDs in different tests comparing between Epileptic and Normal. 95% confidence Interval has been used to find the clinical significance generalized seizures. 

The Statistical software namely SPSS 11.0 and Systat 8.0 were used for the analysis of the data and Microsoft word and Excel have been used to generate graphs, tables etc.

 

 

HyperventilationTest Results Epileptic patients(N=50) Normal subjects(n=50) P value
Fresh IED 2 (4.0%) 0.495
Increased IED 5 (10.0%) 0.056+
Fresh/Increased IED 7(14%)   0.012*
No changes 43 (86.0%) 50 0.012*

 

Table 1 : Effect of Hyperventilation on IED in Epileptic and Normal

+ Suggestive of significance * Moderately significance  ** Strongly significant.

 

 

 

 

 

 

 

 

 

 

Type of epilepsy Number Activation during hyperventilation

A. Generalized seizures

Total-(25) Total- 6 (24.0%)
1)GTCS 10 4 (40.0%)
2)Absence 5 2(40.0%)
3)JME 3
4)Tonic 2
    B.Partial seizures Total(25) Total- 1(4.0%)
1)SPS 13
2)CPS 10 1(10.0%)
3)PS with SG 2

Table 2: Effects of hyperventilation test in different seizure category.

 DISCUSSION

This study was done to test the hypothesis that the activation test such as hyperventilation enhance preexisting abnormalities and / or induce abnormal findings in an otherwise normal EEGs (1). However, hyperventilation test, despite being utilized in routine clinical EEGs for decades, a number of differing views on the usefulness and indications for these procedures exist(1),(2),(3).

In this study, we gathered evidence suggesting that HV is useful activation method, which increase the yield of EEGs  in EEG units.

Hyperventilation test had a significance result in activation of IEDs in epileptics. (P=0.012).

Hyperventilation test could not produce any epileptiform changes or clinical seizures in the EEGs of normal controls.

Our results are consistent with previous findings where hyperventilation test, has shown a great provocative effect in generalized seizures.(2),(4),(5).

Hyperventilation could not produce any epileptiform changes or clinical seizures  in the EEGs of normal controls.

In previous studies also effects of hyperventilation on the EEGs of asymptomatic middle aged adult subjects showed , the incidence of epileptiform activity, is less than 1%.(6).

In our study hyperventilation test showed provocative effect of increased IEDS  in  24% and 1% of the patients with generalized and partial epilepsies, respectively.

If we consider the specific type of epilepsy in our study, effect of hyperventilation was seen maximally in patients of generalized seizures especially in GTCS and absence seizures(40%).Our findings are consistent with the previous studies, where hyperventilation has showed a very good  provocative effect in generalized seizure patients(2),(6),(4),(5),especially absence seizures.

Hyperventilation is the most effective method for activating ictal and interictal epileptiform activity associated with typical absence seizures.

According to Dalby et al (7), hyperventilation will activate seizures in over 80% of untreated children with absence seizures.  As demonstrated by Adams and Lueders (8) hyperventilation is more effective than a 6-hour passive recording in detecting the typical 3-Hz spike-and-wave pattern in children with absence seizures.

In contrary to above findings,a study done by Holmes et al(3), to asses the effectiveness of voluntary hyperventilation (HV) in eliciting seizures in patients with proven epilepsy concluded that, their findings “provide compelling evidence that both localization-related and generalized epilepsies are relatively resistant to routine HV activation in adults and adolescents.

More recently even higher rates of activation in patients with partial seizures have been reported during hyperventilation.(9)(10), which was not the case in our study.

A  study was done to asses effectiveness of HV in  focal seizures during video-EEG monitoring, showed that  HV is an effective method of seizure activation even in focal seizures especially in temporal  lobe epilepsies.(29.5% of patients showed activation).(11)

Blume et al (12)  found out that with routine hyperventilation approximately 50% of those patients with generalized slow spike-and-wave patterns who are able to perform hyperventilation demonstrate activation of epileptiform patterns.

 

In a prospective study, comparision was done between the  hyperventilation (HV), with the recently presented new activational technique of transcranial magnetic stimulation (TMS) in 10 patients with drug-resistant partial epilepsies revealed HV  was a better than TMS in causing activation of the epileptogenic foci .(13)

A recent study revealed that the hyperventilation test has good provocative effect on EEG,s of Jeavons syndrome patients.(14)

In our study Clinical seizure occured in only one epileptic patient(2%) ,which is less as compared to text book concepts and previous studies. (1),(4),(5)  This result can be due to  the effect of antiepileptic drugs and the adult age group of our study as compared to children, where the effects of hyperventilation test are maximal.(1)

 Our data clearly supported the hypothesis that the hyperventilation test enhance preexisting abnormalities and / or induce abnormal findings in an otherwise normal EEGs.

The limitations in our current study was that the effects of hyperventilation tests can be assessed more accurately using sub dural depth electrode EEG recordings taken  in conjunction with  Brain imaging techniques like f MRI scan,  SPECT scan,PET scan.

With study done after discontinuing antiepileptic drugs and standardization of hyperventilation  using blood gas monitoring,results could have been more accurate.

We could not withdraw the antiepileptic drugs because of fear of recurrence of seizures among the epileptic patients and the also because of ethical constraints.

Conclusion

With this study it can be concluded that the hyperventilation test exacerbate or precipitate the epileptiform changes in EEGs and thus avoid missing abnormalities in EEG recordings and increase the yield of EEGs  in epilepsy patients.

When a diagnosis of non-epileptic and epileptic seizures is missed,it may lead to failure to implement appropriate treatment and also unnecessary use of anti-epileptic drugs etc., carry significant risks. 

Correct diagnosis of non-epileptic seizures and epileptic seizures using hyperventilation test is associated with a reduction in health care costs and invasive procedures to diagnose epilepsy can be avoided.

Effects of hyperventilation tests can be assessed more accurately using sub dural depth electrode EEG recordings taken  in conjunction with  Brain imaging techniques

 

ACKNOWLEDGEMENT

The authors would like to thank and acknowledge the immense support of Dr.S.Kumar,Principal and  Dean  M.S.Ramaiah Medical College and Research Hospital.

The authors also acknowledge Dr. K. P. Suresh,Statistician, Animal Nutrition and Physiology for his contribution to work. 

Conflict of Interest-NIL
 

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