A twelve -year-old girl with fever and chronic headache

Prepared by....... Kamornwan Katanyuwong M.D
Virat Sirisanthana M.D..
CC : Low grade fever and throbbing headache for one month.
PI : One month PTA, the patient developed low grade fever and headache. The fever had been noticed in the evening and at night time. She also had throbbing headache during febrile periods. She had no vomiting, blurred vision, nor ataxia. She was treated at a District Hospital with several courses of antibiotics including, amoxicillin, roxithromycin and doxycycline. Because of her persistent headache, she finally was refered to CMU hospital for further investigation and management.
PH : was unremarkable
Significant PE

Temp 38 C, PR 98/min , RR 26/ min , BP 120/7/ mmHg
Neurological exam
Good consciousness
No cranial nerve palsy, no weakness, no cerebellar signs
Normal sensation
Hypereflexia 3+
Blurred disc both eyes, no spontaneous venous pulsation.
No stiffness of neck on admission
Other physical exam appeared normal

Summary of problems

1. low grade fever
2. chronic headache
3. papilledema of both eyes

Laboratory investigation
1. CBC : Hb 13 g/dL , Hct 35 % , WBC 7,700 /cumm (N=62 , L=28 , M=9 ,E=1 ) Plt 373,000 /cumm
2. Electrolyte: Na = 138 mEq/L , K= 4 mEq/Ll , Cl =112 mEq/L, TCO2= 20 mEq/L
3. Chest X- ray: unremarkable study
4. ESR = 54 mm/hr
5. Tuberculin test: 0 mm.
6. Lumbar puncture (done on day 37 of chronic headache) : pressure O/C 30/20 cm.Hg, WBC 194/cumm (P12/L88), no RBC, protein 187 mg/dl, sugar 31mg/dl (Bl. sugar 85 mg/dl), India ink preperation was negative.
7. MRI (done on day 36 of chronic headache): hypointensity of temporal lobe on T1 and patchy hyperintensities in lt temporal lobe, lt thalamus on T2 , FLAIR. Abnormal enhancement after contrast (figure 1 and 2)
Figure 1 MRI 13/11/01 (on day 36 of chronic headache)
Figure 2 MRI 13/11/01 (on day 36 of chronic headache)
Course in the hospital:
Because of above findings she was treated with antituberculous drugs and dexamethasone for 2 weeks. The headache and low grade fever persisted. The repeated MRI (Figure 3) and repeated lumbar were done. The repeated LP demonstrated persistent high pressure, increased protein and low CSF sugar as shown in table 1
Table 1
data \ date
14/11/01 (before anti tuberculous drugs)
20/11/01
27/11/01
29/11/01
pressure O/C (cmHg)
30/20
14/11
29/26
36/18
WBC /cumm(PMN/MONO)
194(12/88)
138(18/82)
72(24/76)
26
RBC cumm
0
0
0
0
protein mg/dl
187
64
108
56
CSFsugar/Bl-sugar mg/dl
31/85
47/-
23/106
28/109
Gram stain
neg.
neg.
neg.
neg.
AFB stain
neg.
neg.
neg.
neg.
PCR for TB
neg.
India ink preperation
neg.
neg.
neg.
pos (figure 4)
CSF cryptococcus titer (Latex)
-
-
pos
pos 1:100
CSF cryptococcus culture
-
-
pos
-
Figure 3 The repeated MRI ( 27/11/01 ) showed a new hyperintensity lesion in the right globus pallidus, right thalamus on T2, could be from subacute hemorrhage.
Figure 4 India ink preperation shows bugging yeasts

Other immunologic investigations:
AntiHIV negative
C3 1066 ug/ml (550-1200 )
CH50 31.8 u/ml ( 20-40 )
IgG 1322 mg/dl 639-1349 )
IgA 138 mg/dl ( 70-312 )
IgM 262 mg/dl (56-352 )

Immunophenotyping: (Before starting antifungal therapy)

 
Normal value
 
% Lymphocytes
25
-
 
% NK
14
-
 
% B cells
25
7-23
 
% T cells (CD3)
59
56-81
 
% T helper (CD4)
28
31-55
 
% T suppressor (CD8)
29
17-38
 
CD4 / CD8 ratio
0.97
0.84-3.05
 
Abs. Lymphocytes
1,258/ cu.mm.
>1,500/cu.mm.
 
Abs. T cells
742/cu.mm.
558-1,948/cu.mm.
 
Abs. T helper
352/cu.mm.
350-1334/cu.mm.
 
Abs. T suppressor
365/cu.mm.
147-812/cu.mm.
 
( WBC count
5,030/cu.mm.)
-


Further course in the hospital:

After the finding of budding-yeast cells and positive cryptococcal titer in the CSF, the treatment was switched to antifungal drug (amphotericin 0.7-1MKD). Two weeks after starting amphotericin B, her CSF culture was negative. Her headache slowly subsided. The repeated MRI is shown in figure 5

Figure 5 MRI after 4 weeks of amphotericin B: showed decrease of abnormal hyperintensity of left termporal and decrease in leptomeningeal enhancement.

The repeated c.s.f. findings show gradual improvement (as in Table 2 and 3)

Table 2
data \ date
6/12/01
(D7 of ampho. B)
11/12/01
(D12 of ampho. B)
14/12/01
(D15 of ampho. B)
pressure O/C (cmHg)
12/10
50/18
41/24
WBC /cumm(PMN/MONO)
-
100(20/80)
26
RBC cumm
trauma
0
0
protein mg/dl
208
159
168
CSFsugar/Bl-sugar mg/dl
31/101
10/101
11
India ink preperation
pos
-
neg
CSF cryptococcus titer (Latex)
1:100
pos 1:100
pos 1:100
CSF cryptococcus culture
-
no growth
no growth
Table 3
data \ date
17/12/01
(D18 of ampho. B)
20/12/01
(D21 of ampho. B)
9/01/02
(last day of ampho. B)
pressure O/C (cmHg)
-
-
-
WBC /cumm(PMN/MONO)
125(20/80)
-
52(4/96)
RBC cumm
-
trauma
1
protein mg/dl
226
292
40
CSFsugar/Bl-sugar mg/dl
10
10
38/135
India ink preperation
pos
-
neg
CSF cryptococcus titer (Latex)
pos 1:100
pos 1:100
pos 1:10
CSF cryptococcus culture
no growth
no growth
no growth

The repeated CBCs show persistent lymphopenia:

Date
Hb (gm%)
Hct( %)
WBC
(/cu.mm)
N (%)
L (%)
M (%)
plt.
Abs. Lymph.
Admission (Nov7)
13.5
36
7,700
62
28
8
373,000
2,156
Prior to antifungal Rx (Nov13)
12.7
38
2,440
63
23
8
260,000
561
Nov 14 (Immuno Lab)
5,030
25
 
1,258
Nov 22
12.6
38
7,500
73
13
12
261,000
1,125
Dec 14
9.8
30
4,560
65
24
9
319,000
1,094
Jan 7 (beforeD/C from hosp.)
9.3
28
6,900
79
12
5
166,000
828
She will be followed up in the OPD.
Diagnosis : Cryptococcal meningitis
What did we learn from this case?

1. Patients with cryptococcosis of the CNS may present as meningitis, meningoencephalitis, and space-occupying lesion.
2. Initial symptoms may be non-specific and physical examination, such as nuchal rigidity was found only 22-44% due to less meningeal reaction.
3. Regarding the CSF examination, an India ink stain for budding yeast yeilds nearly 80 %, whereas positive CSF cryptococcal titer is detected in 93-99%.
4. Imaging studies
> a CT scan maybe normal or non-specific.
> MRI T1 Images show low density lesions in the basal ganglia , hyperdense on T2 and may enhance with godolinium.

BACK to Interesting  Case List