CEYLON J. MED. SCI. (D) Vol. XII, Pt. 1, (Dec. 1963) A Study o f the Electroencephalographic Changes in Subjects Suffering f rom Very Severe Anaemia by DBS. R. S. WATSON, M.B.B.S., PH.D. (lOND.), M. S. NESARAJAH, M.B.B.S. AND S. A. N. PERERA Department of Physiology, University of Geylon. In our study we were interested to find out whether in cases of very severe anaemia, the electrical activity of the brain showed any significant changes. I t is well known that chronic cerebral anaemia could give rise to neuralgic headache, faintness, giddiness, tinnitus and disinclination for effort. Some cases also show somno­ lence, mental apathy, depression, anxiety, excitability, hallucinations and delusions. We were also interested in the study as these cases with very low haemoglobin percentages (40%Hb) would serve as useful subjects for the study of the influence (if any) of anaemic anoxia on the electroencephalograms. Davis, Davis et al (1938) recorded the electroencephalograms of eleven normal men. breathing gas mixtures containing 7-8 to 11-4 percent oxygen. The typical sequence of changes in the E.E.G. was: 1. The average voltage increased slightly and alpha (10/sec.) waves appeared in those records which originally showed none. 2. Alpha voltage decreased, the trains of alpha waves became shorter and the inter­ vals between trains lengthened. 3. Groups of waves a t 8 and 7/sec. appeared at the vertex, while 10/sec. waves continued at the occiput. 4. Irregular delta waves (0-25 or longer) appeared at the vertex and almost immedi­ ately thereafter at the occiput, alternating with the 10/sec. waves. At this stage slight cyanosis was observed, and subjective changes were first reported. Hill and Parr (1950) give a fairly comprehensive review of the work done on the influence of anaemic anoxia on the electroencephalogram. Anaemic anoxia may result from deficient oxygen carrying power of the blood, due either to the lack of sufficient haemoglobin or to fixation of the latter, as in carbon-monoxide poisoning. The following is a summary of the findings in cases of anaemic anoxia:— Slow rhythms have been observed in a few instances of patients with anaemia, but the degree of slow rhythm abnormality seems to depend more on the type of anaemia, than on the haemoglobin value or the red blood cell count. Thus a patient with pernicious anasmia (Hb 7-12 gm/lOOc.c. and R.B.C. 2,090,000/cu.m.m.) was found to have a gene­ ralised abnormality in the E.E.G. of 3-7 cycles/sec. rhythms, of moderate voltage and with or no normal rhythms to be seen; while another patient with severe and chronic anaemia (Hb 2-5 gm/100 c.c. and R.B.C. 630,000/cu.m.m.) had only a mildly abnormal record. 44 WATSON, NBSAKAJAH AND PERERA In general, it appears that in many animal species during extreme anoxia, the electrical activity of the cortex is abolished. In man, the studies deal with less severe degrees of anoxia and the more general finding is the appearance of slow rhythms, widespread delta activity being the most abnormal condition observed. In some instances, a slight increase in frequency of cortical rhythms has been noticed, before tho onset of slow rhythms or arrythmias. Meyer et al (1954) studied the E.E.G. changes in 28 cats and 24 monkeys, on nitrogen breathing. They noticed that the E.E.G. showed decreasing amplitude and slowing of fast activity. Further reduction of the oxygen levels, resulted in flattening of the E.E.G. record except for bursts of slow waves similar to the so called pentobarbital bursts. Re- administration of oxygen recapitulated the sequence of changes. They also noticed that when a zone of cortex was rendered totally anoxic, the alpha rhythm disappeared when the oxygen availability had been reduced by 80%. When the vessel was released, slow, low amplitude activity in the E.E.G. reappeared. after 20% increase in oxygen availability. The E.E.G. was restored to normal when the polarograph reading rose to 80%. Longheed et al (1955) noticed tha t dogs ventilated with 100% nitrogen do not develop E.E.G. changes for 6-8 minutes when hypothermic, but develop electrical silence quickly at normal body temperature. According to them, the electrical silence is not the result of the anoxia, but of the accumulation of waste products, especially carbon dioxide. Method All our 38 subjects wore selected from the Colombo Group of Hospitals and consisted of 28 males (age group 25-65 years) and 10 females (age group 19-35 years). Of the 28 males 5 were in the age group of 65-70 years. In our selection of these 38 cases, special care was taken to see that the subjects were not suffering from any other serious disorder tha t could affect the electroencephalogram. We were mainly concerned with very severe anaemic subjects. Our main criteria for the selection of very severe anaemic subjects was the haemo­ globin percentage of their blood as determined by a photometric method, using the M.R.C. photometer (King et al, 1948). All subjects with haemoglobin percentages of 40 and under were included in our investigation. Of our 38 cases, 9 had a haemoglobin percentage of 16 to 20%; 13 cases 21 to 25%; 2 cases 26 to 30%; 8 cases 31 to 35% and 6 cases of 36 to 40%. The other haematological investigations included the following:— The packed cell volume, the mean corpuscular diameter; the mean corpuscular haemoglobin con­ centration and the red blood cell count. The more reliable index of the degree of anaemia would be the mean corpuscular haemoglobin concentration. In addition to the above invostigations, the oxygen saturation of the bloodinthe vessels of the ear was determined with the use of a Stanco Oximeter. (Stanley Cox Limited, England). I n all our subjects, a complete case history was taken, a general clinical examination was done and this was followed by an E.E.G. examination under identical conditions for each case. For the E.E.G. examination the subject was made to rest on a couch and relax with the eyes closed. Tho records were taken on an eight channel Grass E.E.G. machine using needle electrodes, and both scalp-to-ear and scalp-to-scalp techniques were used, in all cases. Recordings wero made from the frontal, parietal, occipital and temporal areas. Analysis of the records wero made by studying the amplitude and frequency of the recordings. As the control group, we used the same 75 (55 males and 20 females) Ceylonese adults drawn from the ELECTROENCEPHALOGRAPH!- CHANGES IN SUBJECTS 45 Ceylon University, who were used as the controls, for our study ofthe E.E.G. changes in Ceylonese boxers. (Nesarajah et al, 1961). Results The mamfin(lingsinthe 38 cases are tabulatedin the table which includesthe follow­ ing data on each case. Age, Sex, Haemoglobin percentage, Red blood cell count, Packed, cell volume, Mean corpuscular haemoglobin concentration, E.E.G. findings and the results of oximetry. In considering the degree of anaemia, we were guided by two main values— the haemoglobin percentage and the mean corpuscular haemoglobin concentration. The 38 cases selected had haemoglobin percentages less than 40%. On studying these tracings.the most significant change was that in 24 of these cases i.e. 63-2%, a marked diminution in the amplitude of the potentials appeared in most leads. (Fig. I). Tho amplitude of the potentials was in the region of 5-25 microvolts, with an average value of approximately 10-15 microvolts. I t is known that tracings taken from apparently normal individuals may show a marked diminution in amplitude, but the number occurring in a series of controls is never so large. In our controls (75 cases), only eight cases (10-6%) showed a similar fall in the amplitude of the potentials. These diminished amplitude potentials appeared for prolonged periods in most ofthe leads, unlike the controls. 5_> Vn-OrOvoll* — V > Fig. I. Shows the calibration signals of 50 microvolts, and the marked diminished amplitude potentials in all leads. Of the 38 cases selected, 33 cases had a mean corpuscular haemoglobin concentra­ tion le3S than 32. Of these 33 cases. 20 cases i.e. 60-6% showed similar diminished ampli­ tude E.E.G. potentials. 46 WATSON, NESARAJAH AND PERERA These findings seem to suggest some relationship between the E.E.G. patterns and the haemoglobin levels, in the subjects examined. However, it must also be pointed out. that 4 out of the 5 cases with M.C.H.C. values in the range of 32-3S also showed diminished amplitude E.E.G. potentials. These latter cases may represent those cases where dimi­ nished amplitude potentials would have been recorded, even without the severe anaemia, (just like our 10-6% normal controls) I t is therefore highly probable that in very severe cases of anaemia, there is a significant change in the E.E.G. pattern. I t is probable that in these cases of very severe anaemia with low haemoglobin concentrations and diminished number of circulating red blood cells, the biochemical equilibrium inside the neurones is altered, resulting in these changes of electrical activity. I t was not possible to follow these cases after suitable treatment, to see the changes (if any) in the E.E.G. after the blood picture was restored to normal limits. These low amplitude potentials may have some relation to the mental apathy and other changes commonly noticed in clinical cases of very severe anaemia. Our findings agree with the findings of Meyer et al (1954) where in cats and monkeys under nitrogen breathing, decreasing amplitude potentials were noticed. SUMMARY 38 very severe cases of anaemia were examined with a view to studying the influence (if any) of severe anaemia on the E.E.G. changes in the adult. 75 normal adults were used as controls. 24 of the 38 cases (63-2%) showed a significant decline in the amplitude of the E.E.G. potentials as compared to the normals. I t is suggested that E.E.G the changes are probably due to the altered biochemical equilibrium within cerebral neurones and this may be responsible for the clinical changes noticed in these cases of very severe anaemia. ACKNOWLEDGEMENTS We were extremely grateful to the Visiting Physicians and Obstetricians of the General Hospital, Colombo, for allowing us to transport these very severe cases of anaemia to the Department of Physiology. REFERENCES DAVIS, P. A., DAVIS, H. AND THOMPSON, J. 1938.—Progressive changes in Imuran electroencephalogram under low oxygen tension. American J. Pltysiol., 123, 51—52. HILL, D. AND PARR, G. 1950 .—Electroencephalography. Macdonald Press. KINC, E. J., GILCHRIST, M., WOTTON, I. D. P., DONALDSON, R., SISSON, R. B., MACFARLANE, R. G., JOPE, H. M., O'BRIEN, J. R. P., PETERSON, J. M. AND STRANGEWAYS, D. H. 1948.—Determination of Haemoglobin. Precision of Calorimetric Methods. Lancet, 2, 563—566. • LONGHEED, M. W., SWEET, W. H., WHITE, J. C. AND BREWSTER, W. R. 1955.—The use of hypothermia in surgical treatment of vascular lesions. J. of Neurosurgery. 12, 240—255. MEYER, J. S., FANG, H. C. AND DENNY-BROWN, D. 1954.—Polarographic study of cerebral collateral circulation. Archive, of Neurology and Psychiatry. 72, 296—312. NESARAJAH, M. S., SENEVIRATNB. K. N. AND WATSON, R. S. 1961.—Elcctroencephalographic changes in Ceylonese Roxers, Brit Med. Journ. March 25 Vol. 1, p. 866. ELECTROENCEPHALOGRAPHIC CHANGES IN SUBJECTS 47 TABLE Hb% Hb. gm. R.B.C./ P.C.K iVf.C. Oximeter Summary of E.E.C. Findings. lOOc.f. ai.m.m. H.C. Readings% 25 3.7 3,480,000 23 16 81 Diminished amplitude poten­ tials 8-13/scc. of 5-15 micro­ volts amplitude. 25 3.7 2,230,000 20 18.5 87 Within the limits of normal variation 8-13/scc. of 30-50 microvolts amplitude. 25 • 3.7 2,640,000 19 19.5 — Within the limits of normal variation 8-13/scc. of 30-50 microvolts amplitude. 20 2.96 2,290,000 21 14.1 90 Within the limits of normal variation 8-13/sec. of 30-50 microvolts amplitude. 25 3.4 1,350,000 19 17.9 85 Within the limits of normal variation 8-13/sec. of 30-50 microvolts amplitude. 32 4.74 2,740,000 21 22.6 86 Diminished amplitude poten­ tials 8-13/sec. of 5-20 micro­ volts amplitude. 32 4.74 3,710,000 22 21.5 86 Diminished amplitude poten­ tials 8-13/sec. of 5-20 micro­ volts amplitude. 32 4.74 1,350,000 22 21.5 88 Within the limits of normal variation 8-13/scc. of 30-50 •~"~-«iicrovolts amplitude. 32 4.74 2,350,000 18 26.3 83 Diminished amplitude poten­ tials 8-13/scc. of 5-20 micro­ volts amplitude. 40 5.92 2,610,000 23 25.7 82 Within the limits of normal variation 8-13/scc. of 30-50 microvolts amplitude. 40 5.92 2,670,000 19 31.1 82 Widiin the limits of normal variation 8-13/sec. of 30-50 microvolts amplitude. 20 2.% 1,700,000 12 24.7 83 Diminished amplitude poten­ tials 8-13/sec. of 5-20 micro- vols amplitude. 20 2.96 1,260,000 9 32.9 UN Diminished amplitude poten­ tials 8-15 microvolts ampli­ tude. 20 2.96 2,140,000 9 32.9 84 Within the limits of normal variation 8-13/scc. of 30-50 microvolts amplitude. 22 3.25 1,850,000 9 36.1 87 Diminished amplitude poten­ tials 8-13/sec. of 5-20 micro­ volts amplitude. 22 3.25 1,090,000 10 32.5 80 Diminished amplitude poten­ tials 8-13/sec. of 5-20 micro­ volts amplitude. 48 WATSON, NESARAJAH AND PERERA 17. 19 F 22 3.25 1,910,000 11 29.5 84 Within the limits of normal variation 8-13/sec. of 30-50 microvolts amplitude. 18. 32 F 21 3.10 2,210,000 16 19.5 86 Diminished amplitude poten­ tials 8-13/sec. of 5-20 micro­ volts amplitude. 19. 29 F 20 2.96 830,000 10 29.6 85 Diminished amplitude poten­ tials 8-13/sec. of 5-15 micro­ volts amplitude. 20. 30 F 22 3.25 1,610,000 13 25 82 Diminished amplitude poten­ tials 8-13/sec. of 5-15 micro­ volts amplitude. 21. 26 F 40 5.92 2,210,000 22 26.9 88 Within the limits of normal variation 8-13/sec. of 30-50 microvolts amplitude. 22. 30 F 25 3.70 2,370,000 18 20.5 86 Within'the limits of normal variation 8-13/sec. of 30-50 microvolts amplitude. 23. 23 F 35 5.18 2,030,000 18 28.8 80 Within the limits of normal variation 8-13/sec. of 30-50 microvolts amplitude. 24. 27 F 18 2.66 1,000,000 14 19 84 Diminished amplitude poten­ tials 8-13/sec. of 5-15 micro­ volts amplitude. 25. 66 M 30 4.44 2,060,000 16 27.8 84 Diminished amplitude poten­ tials 8-13/sec. of 5-15 micro­ volts amplitude. 26. 35 F 40 5.92 2,350,000 21 28.2 86 Diminishsd amplitude poten­ tials 8-13/sec. of 5-15 micro­ volts amplitude. 27. 60 M 20 2.92 2,230,000 12 24.7 84 Diminished amplitude poten­ tials 8-13/sec. of 5-15 micro- 28. 60 M 31 4.59 2,290,000 17 27 88 Diminished amplitude poten­ tials 8-13/sec. of 5-15 micro­ volts amplitude. 29. 55 M 35 5.18 3,040,000 19 27.2 88 Within the limits of normal variation 8-13/sec. of 30-50 microvolts amplitude. 30. 35 M 35 5.18 2,360,000 19 27.2 91 Diminished amplitude poten­ tials 8-13/sec. of 5-15 micro­ volts amplitude. 31. 35 M 25 3.7 1,480,000 14 26.4 89 Within the limits of normal variation 8-13/sec. of 30-50 microvolts amplitude. 32. 40 M 25 3.7 1,820,000 19 19.5 85 Diminished amplitude poten­ tials 8-13/sec. of 5-15 micro­ volts amplitude. 33. 50 M 20 2:96 2,350,000 16 18.5 90 Diminished amplitude poten­ tials 8-13/sec. of 5-15 micro­ volts amplitude. 34. 51 M 25 3.7 2,370,000 21 17.6 89 Diminished amplitude poten­ tials 8-13/sec. of 5-15 micro- BLECTROENCEPHALOGRAPHIC CHANGES IN SUBJBCTS 49 38 5.62 30 4.44 20 2.96 40 5.92 2,380.000 18 2,760,000 15 1,420,000 11 2,110,000 18 31.2 87 29.6 81 26.9 84 32.9 82 Diminished amplitude poten­ tials 8-13/sec. of 5-15 micro­ volts amplitude. Diminished amplitude poten­ tials 8-13/sec. of 5-15 micro­ volts amplitude. Diminished amplitude poten­ tials 8-13/sec. of 5-15 micro­ volts amplitude. Diminished amplitude poten­ tials 8-13/sec. of 5-15 micro­ volts amplitude.