Clinical
Utility of CSF and Serum CRP in Children Clinically Diagnosed as
Cases of Meningitis.
INTRODUCTION :
Literature shows various studies on behavioural problems in
epilepsy with contradictory & sometimes inconclusive results.
Association of behavioural problems with epilepsy varies with
-
- Age of onset,
- Frequency of seizures
- Type of seizure
- Duration of epilepsy
There is paucity of information where several of these factors
are studied simultaneously so that the true effect of each could
be ascertained by partialling out the influence of other
confounding variable.
In the present study we have attempted to study effect of
these variables of epilepsy on behavioral disorders by using Conners
Parent Rating scale – 48.
OBJECTIVE :
To compare the behavioural disorders in children with epilepsy
with controls and to determine the effect of high risk factors
such as :
- Age of onset of epilepsy.
- Duration of epilepsy
- No. of seizures since onset of epilepsy and
- Clinical type of seizure on behavioral disorders in
children with epilepsy aged 3 – 17 years.
DESIGN : CASE CONTROL STUDY :
MATERIAL AND METHODS :
Study sample : 80 children with epilepsy
Control : 80 children without epilepsy
Age group, SE Status and literacy of parents were comparable.
LEARNING disorder was studied in 65 children with epilepsy and
65 controls whose age was more than 6 years.
INCLUSION CRITERIA FOR CASES :
- Age group 3 – 17 years.
- Those having recurrent i.e., 3 or more
seizures episodes.
- Those having normal family background
i.e.,
-
- both parent alive
- No divorce of parents and
- No family h/o psychiatric
disorders.
- No MR according to WHO criteria.
SCALES USED :
- Conners Parent rating scale – 48.
- Socio-economic scale : modified Kuppuswamy
scale.
STATISTICAL ANALYSIS :
By using Chi Square test and Fischer exact
test.
INTRODUCTION :
Prompt and precise differentiation between
various forms of CNS infection is critical and difficult problem
for treating clinician. A number of studies have strongly
suggested that either Serum or CSF measurement CRP could reliably
discriminate between various forms of CNS infections.
The present study was designed to evaluate the
clinical utility of CSF and serum CRP in children clinically
diagnosed as cases of meningitis.
MATERIAL & METHODS :
Age : Neonates and children below the
age of 12 years.
Patients were categorised into 4 groups
(Pyogenic Meningitis, Tuberculous Meningitis, Viral Meningitis
& /or Encephalitis & No-Meningitis) based on clinical and
laboratory findings.
CRITERIA FOR DIAGNOSIS :
- PYOGENIC MENINGITIS(PM) (n = 86)
Criteria used: >2 of the following
- Turbid / Purulent CSF
- CSF cell count above the
prescribed norms for age with
predominant Polymorphonuclear leucocytosis.
- CSF protein raised above the
prescribed norms for age and reduced CSF sugar.
- Identification of bacteria on Gram
stain or culture.
- TUBERCULOUS MENINGITIS (n = 10)
Diagnostic critera used: Essential + >2 Supportive criteria
ESSENTIAL :
CSF showing :
- Predominant lymphocytic
pleocytosis > 50 cells / mm 3
- Protein > 60 mg / dl
- Sugar < 2 / 3 of blood sugar
SUPPORTIVE :
- History of fever of > 2
weeks
- Positive family history of
tuberculosis, either sputum positive or
radiology positive and sputum negative or
both positive.
- Positive tuberculin test.
- Superficial adenitis of
tuberculous etiology proved by FNAC /
histopathology.
- Positive radiological
evidence of tuberculosis in chest.
- CT scan evidence of basal
exudate and / or ventricular dilatation.
- VIRAL MENINGITIS / VIRAL
ENCEPHALITIS (VM/VE) (n=8)
All the following criteria were essential :
- Short history
- Clinical evidence of
associated viral infection in other parts
of the body like sore throat,
gastroenteritis, conjunctivitis, rash,
etc.
- Normal cytology or
pleocytosis with Iymphocytic predominance
and sugar > 45 mg / dl and marginal
rise of proteins (50 – 200 mg / dl).
- Negative CSF gram stain or
culture.
Viral cultures could not be done.
OBSERVATIONS :
- Conners Scale T-score > 50 % and < 70 % = Mild
behavioral disorder.
May not need t/t.
- T score > 70 % = Severe behavioral disorder
Need T/T for behavioral disorders.
TABLE I : SHOWING THE INCIDENCE AND SEVERITY
OF BEHAVIOURAL DISORDERS IN CHILDREN WITH EPILEPSY AND CONTROLS.
| Behavioural
disorders |
Cases
T-Score
|
Control
T-Score
|
P –VALUE
|
50 to 70%
|
> 70%
|
Total
|
50 to 70%
|
> 70%
|
Total
|
50 to 70%
|
> 70%
|
| 1) Conduct
Disorder |
27
|
13
|
40
|
18
|
1
|
19
|
< 0.0001
|
< 0.05
|
| 2)
Learning Disorder |
33
|
6
|
39
|
11
|
0
|
11
|
< 0.0001
|
> 0.05
|
| 3)
Psychosomatic |
41
|
7
|
48
|
29
|
3
|
32
|
< 0.05
|
> 0.05
|
| 4)
Impulsive Hyperactive |
33
|
4
|
37
|
16
|
0
|
16
|
< 0.01
|
> 0.05
|
| 5) Anxiety
Disorder |
34
|
4
|
38
|
24
|
1
|
25
|
> 0.05
|
> 0.05
|
TABLE II : SHOWING THE EFFECT OF AGE
OF ONSET OF EPILEPSY ON BEHAVIOURAL DISORDER
| Clinical Type of seiz-ures
|
Behavioural Disorders
(T-Score)
|
Conduct
|
Learning
|
Psychomatic
|
Impulsive –
Hyperactive
|
Anxiety
|
50to70 %
|
>70 %
|
Abs-ent
|
50to70 %
|
>70 %
|
Abs-ent
|
50to70 %
|
>70 %
|
Abs-ent
|
50to70 %
|
>70 %
|
Absent
|
50to70 %
|
>70 %
|
Abs-ent
|
< 5 Yrs
|
8
|
10
|
19
|
14
|
6
|
3
|
15
|
5
|
17
|
20
|
4
|
13
|
19
|
2
|
16
|
> 5 Yrs.
|
19
|
3
|
21
|
19
|
0
|
23
|
26
|
2
|
15
|
13
|
0
|
30
|
15
|
2
|
26
|
P Value
|
>50%
|
>70%
|
|
>50%
|
>70%
|
|
>50%
|
>70%
|
|
>50%
|
>70%
|
|
>50%
|
>70%
|
|
| |
>0.05
|
<0.05
|
|
<0.05
|
=0.01
|
|
>0.05
|
>0.05
|
|
<0.01
|
>0.05
|
|
>0.05
|
>0.05
|
|
TABLE III : SHOWING THE EFFECT OF
NUMBER OF SEIZURES SINCE ONSET OF EPILEPSY ON BEHAVIOURAL
DISORDERS
| |
BEHAVIOURAL DISORDERS
(T-Score)
|
Conduct
|
Learning
|
Psychomatic
|
Impulsive –
Hyperactive
|
Anxiety
|
No. of seizure
|
50 to 70%
|
>70%
|
Absent
|
50 to 70%
|
>70%
|
Absent
|
50 to 70%
|
>70%
|
Absent
|
50 to 70%
|
>70%
|
Absent
|
50 to 70%
|
>70%
|
Absent
|
3-6
|
18
|
3
|
35
|
16
|
2
|
26
|
28
|
4
|
24
|
17
|
2
|
37
|
23
|
2
|
21
|
> 6 .
|
9
|
10
|
5
|
17
|
4
|
0
|
13
|
3
|
8
|
16
|
2
|
6
|
11
|
2
|
11
|
P Value
|
>50%
|
>70%
|
|
>50%
|
>70%
|
|
>50%
|
>70%
|
|
>50%
|
>70%
|
|
>50%
|
>70%
|
|
| |
<0.001
|
<0.05
|
|
=0.0001
|
>0.05
|
|
>0.05
|
>0.05
|
|
<0.001
|
>0.05
|
|
>0.05
|
>0.05
|
|
TABLE IV : SHOWING THE EFFECT OF DURATION OF
EPILEPSY ON BEHAVIOURAL DISORDERS
Durat-ion of epile-psy
|
BEHAVIOURAL DISORDERS
(T-SCORES)
|
Conduct
|
Learning
|
Psychomatic
|
Impulsive –
Hyperactive
|
Anxiety
|
50 to 70 %
|
>70%
|
Absent
|
50 to 70 %
|
>70%
|
Absent
|
50 to 70 %
|
>70%
|
Absent
|
50 to 70 %
|
>70%
|
Absent
|
50 to 70 %
|
>70%
|
Absent
|
< 2 yrs
|
6
|
3
|
24
|
6
|
0
|
17
|
18
|
1
|
19
|
12
|
0
|
21
|
15
|
0
|
18
|
> 2 yrs
|
22
|
9
|
16
|
28
|
5
|
9
|
23
|
6
|
13
|
21
|
4
|
22
|
19
|
4
|
24
|
P Value
|
>50%
|
>70%
|
|
>50%
|
>70%
|
|
>50%
|
>70%
|
|
>50%
|
>70%
|
|
>50%
|
>70%
|
|
| |
<0.001
|
>0.05
|
|
<0.001
|
=12.1
|
|
>0.05
|
>0.05
|
|
>0.05
|
>0.05
|
|
>0.05
|
>0.05
|
|
TABLE V : COMPARING THE EFFECT OF
GENERALISED SEIZURES AND PARTIAL SEIZURES ON BEHAVIOURAL
DISORDERS
Clinical
Type of seizure
|
BEHAVIOURAL DISORDERS
(T-SCORES)
|
Conduct
|
Learning
|
Psychosomatic
|
Impulsive –
Hyperactive
|
Anxiety
|
50 to 70 %
|
>70%
|
Absent
|
50 to 70 %
|
>70%
|
Absent
|
50 to 70 %
|
>70%
|
Absent
|
50 to 70 %
|
>70%
|
Absent
|
50 to 70 %
|
>70%
|
Absent
|
General-ised Seizure
|
19
|
11
|
20
|
26
|
3
|
21
|
27
|
4
|
19
|
24
|
3
|
23
|
20
|
3
|
27
|
Partial Seizures
|
8
|
2
|
20
|
7
|
3
|
20
|
14
|
3
|
13
|
9
|
1
|
20
|
14
|
1
|
15
|
P Value
|
>50%
|
>70%
|
|
>50%
|
>70%
|
|
>50%
|
>70%
|
|
>50%
|
>70%
|
|
>50%
|
>70%
|
|
| |
<0.05
|
>0.05 |
|
>0.05
|
>0.05
|
|
>0.05
|
>0.05
|
|
>0.05
|
>0.05
|
|
>0.05
|
>0.05
|
|
RESULTS :
- Relation of Behavioural disorders &
epilesy:
-
- Conduct-----------Highly
significant
- Learning----------- Highly
significant
- Psychosomatic-----Significant
- Impulsive
hyperactive-----Significant
- Anxiety------------Not significant
- High risk factors for increase in
incidence of : conduct & learning were:
- Age of onset of epilepsy < 5
years.
Total number of
seizures > 6
Duration of epilepsy > 2
years.
- High risk factors for increase in
incidence of impulsive hyperactivity :
- There was no effect of these epileptic
variables on psychosomatic and anxiety disorders.
- Irrespective of clinical type of seizure
the incidence of behavioural disorders doesn’t vary.
CONCLUSION :
- THE BEHAVIOURAL DISORDERS IN CHILDREN WITH
EPILEPSY WERE SIGNIFICANTLY MORE AS COMPARED TO CONTROL
GROUPS. (P < 0.05).
- BEHAVIORAL DISORDERS WERE MORE SEVERE
REQUIRING INTERVENTION WHEN
-
- AGE ONSET OF EPILEPSY
WAS< 5 YEARS AND
- TOTAL NUMBER OF SEIZURES
> 6.
- CHILDREN WITH EPILEPSY SHOULD BE ASSESSED
FOR BEHAVIOURAL DISORDERS BEFORE STARTING ANTI-EPILEPTIC
MEDICATION.
D) NO MENINGITIS GROUP (n =
25) :
This group included patients of febrile
convulsions undergoing lumbar puncture for suspected meningitis.
Diagnostic Criteria used were :
- First convulsion experienced by the child
associated with temperature more than 38 0 C.
- Child is less than 6 years.
- No evidence o f CNS infection or
inflammation.
- The child has no acute systemic or
metabolic disorder.
CSF – CRP (qualitative) and serum CRP
(qualitative &semiquantitative) test was done at diagnosis in
86 children with Pyogenic meningitis, 10 children with TBM, 8
children with VM / VE and 25 children with no-meningitis group
using latex agglutination test.(Sensitivity of the kit was
6ug/ml). Serial doubling dilution of the serum was done with 0.9%
saline Statistical analysis was done using students
t-test.
RESULTS :
TABLE-1 QUALITATIVE SERUM & CSF TEST IN
VARIOUS GROUPS :
Sr. No.
|
Dis.groups
|
No. of cases
|
Serum CRP Test
|
CSF – CRP Test
|
Positive
|
Negative
|
Positive
|
Negative
|
1
|
PM
|
86
|
86 (100%)
|
0 (00%)
|
43 (50%)
|
43 (50)
|
2
|
TBM
|
10
|
10 (100%)
|
0 (00%)
|
0 (00%)
|
0 (00)
|
3
|
VM / VE
|
8
|
6 (75%)
|
2 (25%)
|
0 (00%)
|
0 (00)
|
4
|
No
meningitis
|
25
|
16 (64%)
|
9 (36%)
|
0 (00%)
|
0 (00)
|
-
- Qualitative serum CRP test could
detect all cases of PM but could not
differentiate it from other groups.
- Qualitative CSF CRP test was
positive in 50 % cases of PM & negative in
all other groups.
- Qualitative CSF CRP test could
differentiate PM from other groups with - 50 %
sensitivity,
100 % specificity &
positive predictive value- 50 % negative predictive
value.
TABLE – 2 : SEMIQUANTATIVE SERUM CRP LEVELS IN
DIFFERENT GROUPS ON ADMISSION
| |
Group
|
Range
(mg/l)
|
Mean
(mg/L)
|
SD
(mg/L)
|
A
|
PM
|
96 –
768
|
297.81
|
134.55
|
B
|
TBM
|
24 –
96
|
55.20
|
22.77
|
C
|
VM / VE
|
0 –
24
|
11.25
|
9.32
|
D
|
No
meningitis
|
0 –
24
|
7.68
|
7.25
|
- Serum CRP levels ³ 96 mg/L Ü In
100 % patients of PM.
- Serum CRP levels ³ 192 mg/l Ü In
93.03 % of patients of PM.
- A cut off limit of 96 mg/L can
differentiate PM from other groups with
-
- 100 % sensitivity and
negative predictive value,
- 95.35 % specificity
- 97.72 % positive
predictive value.
TABLE-3: SIGNIFICANCE OF VARIATIONS OF MEAN SEMIQUANTATIVE
SERUM CRP LEVELS IN DIFFERENT GROUPS.
S. No.
|
Compared
groups
|
P
– value
|
Sgnificance
of difference
|
1
|
A : B
|
P <
0.001
|
H.S.
|
2
|
A : C
|
P <
0.001
|
H.S.
|
3
|
A : D
|
P <
0.001
|
H.S.
|
A – PM B – TBM C – VM / VE D
– No Meningitis HS – Highly
significant
The mean semiquantative serum CRP levels
in PM was significantly high compared to
other groups. (P < 0.001).
CONCLUSION :
IN A CHILD WITH CLINICAL SUSPICION OF MENINGITIS :
- POSITIVE QUALITATIVE CSF–CRP TEST IS DIAGNOSTIC OF
PYOGENIC MENINGITIS.
- NEGATIVE QUALITATIVE SERUM CRP TEST EXCLUDES BACTERIAL
MENINGITIS.
- SERUM CRP LEVEL >96 mg/L CAN DIFFERENTIATE PYOGENIC
MENINGITIS FROM OTHER GROUPS WITH
-
- 100 % SENSITIVITY & NEGATIVE PREDICTIVE
VALUE.
- 95.35 % SPECIFICITY &
- 97.72 % POSITIVE PREDICTIVE VALUE.
- CRP TEST IS A DIAGNOSIS OF CHEAP AND RAPID
BEDSIDE TEST FOR PYOGENIC MENINGITIS.
