결핵성 뇌막염에 있어서 뇌척수액내 Adenosine Deaminase 활성도의 진단적 가치에 관한 연구

Abstract

[한글]

결핵상 뇌막염은 우리나라에서 비교적 흔한 중추신경계의 염증성 질환으로서 그 예후는 치료를 시작하는 시기와 밀접한 관계가 있기 때문에 조기진단이 무엇보다도 중요하지만 대부분의 경우 결핵성 뇌막염의 진단은 임상적인 소견에 의존할 수 밖에 없는 실정이다.

본 연구에서는 세균학적 검사나 임상상 결핵성 뇌막염으로 진단된 환자 25예와 무균성 뇌막염으로 진단된 27예, 기타 다양한 신경계의 기질적 병변 이 있는 49예 및 신경계에 병변이 없으며 정상 뇌척수액 소견을 보였던 정상 대조군 27예를 대상으로 뇌척수액 Adenosine deaminase(ADA) 활성도를 측정하여 다음과 같은 결과를 얻었다.

결핵성 뇌막염군, 무균성 뇌막염군, 기타 신경계 질환군 및 정상 대조군에서의 뇌척수액 ADA 활성도는 각각 평균 11,16 ± 0.83unit/L(범위 2.2-34.8unit/L), 2.96 ± 1.75unit/L (0.2-7.5unit/L), 2.14 ± 1.79unit/L(0.1-7.3unit/L), 1.09 ± 0.53unit/L(0.4-2.2unit/L)로 각 군 사이에 통계학적으로 유의한 차이가 있었고 특히 결핵성 뇌막염군에서 다른 경우보다 더욱 현저하였다. 반복 검사를 제외한 첫번째 뇌척수액에서의 ADA 활성도만

을 보면 결핵성 뇌막염에서는 분포가 4.5-34.8unit/L로서 모두 4unit/l 이상이었으며 6unit/L 이상은 25예중 22예(88%), 8unit/L 이상은 17예(68%)에서 관찰되었다. 이에 비하여 무균성 뇌막염의 뇌척수액 ADA 활성도는 모두 6unit/L 이하였지만 4unit/L 이상인 환자가 27예중 3예(11%)였으며 기타 질환군에서는 모두 8unit/L 이하로서 6unit/L 이상의 환자가 45예중 4예(8%)였는데 다형성 교아종, 중주신경계 낭창, 시신경염 및 당뇨병성 동안신경마비 환자에서 비교적 높이 증가되어 있었다. 각 군에서 일반 뇌척수액 검사시 흔히 측정하는 매개변수들(단백양, 총백혈구수, 단핵백혈구수, 당치)과 뇌척수액 ADA활성도와는 뚜fut한 상관관게를 보이지 않았다. 결핵성 뇌막염의 치료경과에 따른 뇌척수액 ADA 활성도의 변화를 보면 16예중 7예(43.8%)애서 처음 검사시 보다 약 2-14일 후에 시행한 두 번째 검사에서 오히려 증가하는 양상을 보였는데 그 이후 점차 감소하는 경향이 있었고 치료 3주 후부터 그 감소가 뚜렷하여졌다.

이상의 결과에서 뇌척수액 ADA 활성도는 신경계의 여러 질환에서 비 특이적으로 증가 하지만 특히 결핵성 뇌막염에서 현저한 증가를 보이는 바 무균상 뇌막염과의 감별진단에 큰도움을 줄 것으로 생각된다.

A Study on the Diagnostic Value of Cerebrospinal Fluid Adenosine Deaminase Activity

in Tuberculous Meningitis

Ji Hoe Heo

Department of Medical Science The Graduate School Yonsei University

(Directed by Professor Ki Whan Kim, M.D.)

Tuberculous meningitis is still relatively common infectious disease of central

nervous system in Korea. The early diagnosis of tuberculous meningitis is crucial

because its prognosis is closely linked to the stage at which treatment is

initiated. The diagnosis however, will of ten have to be made on purely

circumferential evidences due to unsuccessful bacteriological proof. Cerebrospinal

fluid adenosine deaminase(ADA) activities were measured in 25 cartes of tuberculous

meningitis, 27 cases of asepic meningitis, 49 cartes of miscellaneous neurologic

conditions and 2f cages of normal control. The mean CSF ADA activities in

tuberculous meningitis, aseptic meningitis, miscellaneous neurologic conditions and

normal controls were 11.16 ± 6.83 unit/L(range 2.2-34.8 unit/L), 2.96 ±

1.75unit/L(0.2-7.5unit/7), 2.14 ± 1.79unit/L(0.1- 7.3unit/L), and 1.09 ±

0.53unit/L(0.4-2.2unit/L) respectively, which show statistically significant

differences in each others. CSF ADA activity was most prominently increased in

tuberculous meningitis especially in its initial measurement. Of 25 patients with

tuberculous meningitis, all had initial ADA 4unit/L 22 cases(88%) above 6unit/L,

and 17cases(68%) above 8unit/L. In contrast, most patients with aseptic meningitis

had activities below 4unit/L, but in 3 of 27 patients(11%) the activity was in the

range of 4-6unit/L. ADA activities in most patients with miscellaneous neurologic

conditions were also below 4unit/L except 4 of 49 patients(8%) in the range of

6-8unit/L. There were no statistically significant correlation between ADA activity

and routine parameters in spianl fluid analysis. CSF ADA activitis were relatively

high till 2 weeks after treatment in tuberculous meningitis and were preceded by

initial rise on fellow-up ADA measurements in 7 of 16 patients(43.8%). CSF ADA

activities were relatively high in glioblastoma multiforme, central nervous system

lupus, optic neuritis and diabetic oculomotor nerve palsy.

From these results, even though CSF ADA is nonspecifically increased in various

neurologic diseases, most prominent increment is seen in the patients with

tuberculous meningitis. And ADA measurement in CSF seems to be valuable in

differentiating tuberculous meningitis from aseptic meningitis.

[영문]

Tuberculous meningitis is still relatively common infectious disease of central nervous system in Korea. The early diagnosis of tuberculous meningitis is crucial because its prognosis is closely linked to the stage at which treatment is initiated. The diagnosis however, will of ten have to be made on purely

circumferential evidences due to unsuccessful bacteriological proof. Cerebrospinal fluid adenosine deaminase(ADA) activities were measured in 25 cartes of tuberculous meningitis, 27 cases of asepic meningitis, 49 cartes of miscellaneous neurologic

conditions and 2f cages of normal control. The mean CSF ADA activities in tuberculous meningitis, aseptic meningitis, miscellaneous neurologic conditions and normal controls were 11.16 ± 6.83 unit/L(range 2.2-34.8 unit/L), 2.96 ± 1.75unit/L(0.2-7.5unit/7), 2.14 ± 1.79unit/L(0.1- 7.3unit/L), and 1.09 ± 0.53unit/L(0.4-2.2unit/L) respectively, which show statistically significant differences in each others. CSF ADA activity was most prominently increased in tuberculous meningitis especially in its initial measurement. Of 25 patients with

tuberculous meningitis, all had initial ADA 4unit/L 22 cases(88%) above 6unit/L, and 17cases(68%) above 8unit/L. In contrast, most patients with aseptic meningitis had activities below 4unit/L, but in 3 of 27 patients(11%) the activity was in the range of 4-6unit/L. ADA activities in most patients with miscellaneous neurologic conditions were also below 4unit/L except 4 of 49 patients(8%) in the range of 6-8unit/L. There were no statistically significant correlation between ADA activity

and routine parameters in spianl fluid analysis. CSF ADA activitis were relatively high till 2 weeks after treatment in tuberculous meningitis and were preceded by initial rise on fellow-up ADA measurements in 7 of 16 patients(43.8%). CSF ADA

activities were relatively high in glioblastoma multiforme, central nervous system lupus, optic neuritis and diabetic oculomotor nerve palsy.

From these results, even though CSF ADA is nonspecifically increased in various neurologic diseases, most prominent increment is seen in the patients with tuberculous meningitis. And ADA measurement in CSF seems to be valuable in differentiating tuberculous meningitis from aseptic meningitis.