HABILIDADES PEDAGÓGICAS Y DIDÁCTICAS, 1.1-1

Cardiac sympathetic and parasympathetic function tests were conducted under standardized conditions, with measurements taken in a silent room at a temperature of 22±2^oC. ECG recording from lead II was carried out during the parasympathetic tests.

Subjects had been requested during recruitment to abstain from food on the day of the tests and to take only the regular dose of their anti-epileptic medications. The tests were done from 8 - 10 a.m. in order to ensure that the adrenergic response to hunger did not interfere with the test results. The procedure was first demonstrated to each subject and it was ascertained that the method had been mastered before commencement of testing. A standardized interval of 2 minutes was maintained between each test to allow for recovery of baseline parameters before continuation to other tests.

The sympathetic tests included blood pressure (BP) responses to sustained isometric handgrip and standing, while the parasympathetic tests included heart rate response to deep breathing, valsalva manoeuvre and standing.

3.9.1 HEART RATE CHANGE WITH DEEP BREATHING

In the supine position each subject was requested to breathe at the rate of 6 cycles per minute i.e each inspiration and expiration lasting 5 seconds. Continuous ECG recording was conducted during this test and periods of inspiration and expiration were distinctly marked off with a pen. The deep breathing difference (ΔHR) which is

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the difference between the maximum heart rate and the minimum heart rate was determined for each subject. The test was done twice and the higher ΔHR was selected for each participant.

3.9.2 HEART RATE CHANGE DURING VALSALVA MANOEUVRE

Each participant was asked to blow into the empty barrel of a 20mL syringe (serving as mouthpiece) connected to the tubing of a standard mercury manometer until a pressure of 40 mmHg was attained. The subject was requested to maintain this pressure for 15 seconds and the strain was then discontinued while continuing to record the ECG tracing from lead II for up to 20 seconds thereafter. This test was done 3 times in succession for each subject.

The Valsalva ratio was determined for each subject on the 3 occasions indicated, using the following formula: maximum RR interval after release of strain /minimum RR interval during strain. The highest of the three ratios was taken as the representative ratio.

3.9.3 HEART RATE AND BLOOD PRESSURE CHANGES WITH STANDING The heart rate response to postural change (i.e rising from the supine position) was determined with ECG recorded from the lead II. The ratio of the longest RR interval at 30 seconds after standing to the shortest RR interval at 15 seconds after postural change was determined. This ratio was regarded as the 30/15 ratio.

The blood pressure of each subject at baseline was noted. After requesting the subject to stand, the blood pressure was then measured at 2 minutes, 5 minutes and 7 minutes.

The difference between the baseline blood pressure and the lowest blood pressure after standing was determined.

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3.9.4 BLOOD PRESSURE RESPONSE TO SUSTAINED ISOMETRIC HAND GRIP

Each subject was taught how to contract a hand grip dynamometer with maximal effort using the dominant hand. The maximum voluntary contraction (MVC) was thereby determined, and following a 1 minute relaxation the subject was then asked to contract the dynamometer at 30% of MVC for 4 minutes. Blood pressure was measured after contraction at 1, 2 and 4 minutes in the contralateral arm. The change in diastolic blood pressure from baseline, just before the release of isometric work was determined.

3.9.5 INTERPRETATION OF CARDIAC AUTONOMIC FUNCTION TESTS The cardiac autonomic function tests were interpreted as normal, borderline or abnormal based on the values earlier identified by Ewing et al ⁹⁹. The grade of cardiac autonomic neuropathy was then determined according to the recommendations of Ewing et al as follows:

1) Normal: all five tests normal or one borderline.

2) Early: one of HR/BP based tests abnormal or two tests borderline.

3) Definitive: two or more HR based tests abnormal.

4) Severe: two or more HR based tests are abnormal with one or both BP based tests abnormal.

Table 12 shows a representation of the reference ranges for bedside cardiac autonomic function tests.

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Table 12: An interpretive scheme for cardiac autonomic function tests Test Parameter Value Category Score Deep breathing

test

∆ HR(beats per minute)

>15 11-14

≤ 10

Normal Borderline Abnormal

0 1 2 Valsalva

manoeuvre

Valsalva Ratio

≥1.21 1.11-1.20

≤ 1.10

Normal Borderline Abnormal

0 1 2 Lying to standing

ECG

Lying to standing BP

30:15 ratio ≥ 1.04 1.01-1.03

≤1.00

Normal Borderline Abnormal

0 1 2 Fall in

systolic pressure (mmHg)

≤ 10 11-20

>20

Normal Borderline Abnormal

0 1 2

Handgrip test Change in diastolic blood pressure (mmHg)

≥16 11-15

≤ 10

Normal Borderline Abnormal

0 1 2

Key: BP- Blood Pressure, ECG- electrocardiogram, ∆HR (deep breathing difference), mmHg (millimetres of mercury).

80 3.10 STATISTICAL ANALYSIS

Statistical analysis was carried out with the Statistical Package for Social Sciences software version 17 (SPSS 17.0). Characteristics of the subjects such as age, body mass index (BMI), resting heart rates and blood pressures were expressed using means and standard deviations. Seizure variables such as age of onset, duration of epilepsy, seizure frequency and treatment duration as well as the results of the autonomic function tests of patients and controls were similarly expressed using means and standard deviations. Gender categories were expressed as frequencies and percentages as were seizure variables like seizure type, seizure periodicity and anti-epileptic drug type.

Chi square cross-tabulation was done to determine the difference in occurrence of autonomic symptoms between epilepsy patients and healthy controls and to determine the association between autonomic symptoms and cardiac autonomic neuropathy in epilepsy patients. The occurrence of CAN was dichotomized into present or absent and its association with seizure variables was tested using chi-square cross-tabulation statistics. The means of the autonomic function test results of patients and controls were compared using parametric independent samples t-test. Seizure variables that had a statistically significant association with CAN were further tested by binary logistic regression to determine the independent predictors of CAN. Statistical significance was consistently defined by a P-value ≤ 0.05.

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CHAPTER FOUR 4.0 RESULTS

There were eighty epilepsy patients and eighty age- and sex-matched healthy controls involved in this study.

4.1 DEMOGRAPHIC CHARACTERISTICS OF THE STUDY POPULATION