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【Presentation of a
Case】
A 29-year-old man was admitted because
of intermittent headache and dizziness for one month. He
had been otherwise well before until three months before admission,
when he began to experience frequent episodes of oral
ulcer. One month earlier prior to admission, fever and lassitude
developed, which were associated with intermittent dizziness,
neck soreness, and mild headache. The headache lasted
two or three minutes, at a frequency of about three times
daily, and there was no predisposing factors, such as cough
or posture change. He was seen at another hospital without
benefit after taking some medicine. Two weeks before this
admission, dizziness and near-fainting occurred when he returned
from work, followed by tinnitus, for which he sought medical
help at the emergency department (ED). Examinations at ED
showed no fever, vertigo, focal neurological signs, meningeal
signs, or abnormality in the ENT field. He developed nausea
and vomiting after discharge from ER, and the medications
(acetaminophen and NSAIDs) failed to relieve his
headache. He went to a neurology outpatient clinic of another
hospital two days later, when an EEG study showed abnormal
findings suggestive of lesions involving both cerebral
hemispheres. The headache was fullness in sensation and
localized at the parietal region, with an increasing frequency
and duration, lasting for two or three hours, and it was
associated with blurred vision and tinnitus. Over the past
month, he also felt migratory headache. Because of worsening
headache, he underwent a brain CT at another hospital, which
was reported to be negative 4 days before this admission. He
was admitted to our ED again because of worsening headache.
On admission, his consciousness
was clear and oriented. The body temperature was 36.0℃. The
pulse rate was 55 bpm. The respiratory rate was 20/min. The
blood pressure was 123/84 mmHg. His conjuctiva was pink and
his sclera was not icteric. The pupil was isocoric with prompt
light reflex. The throat was mildly injected without ulcer or
enlarged tonsils. The neck was mildly stiff, with negative
Kernig's and Brudzenski's signs. The chest wall expansion was
symmetric and breath sounds were clear bilaterally. The heart
beats were regular without murmur. The abdomen was soft and
flat, with normoactive bowel sound. Neither local tenderness
nor rebound tenderness was found. The liver was not palpable
and the estimated span was 10 cm along the right middle
clavicular line by percussion. The spleen was impalpable.
Extremities were freely movable without purpura, petechia or
edema. The neurological examinations revealed findings within
normal limits (include higher cortex function, cranial nerve,
motor, sensory and autonomic systems, cerebellum functions).
There was no diplopia.
The results of the laboratory
tests are as follows:
1. CBC/DC
|
|
WBC
K/μL |
RBC
M/μL |
Hb
g/dL |
Hct
% |
MCV
FL |
PLT
K/μL |
Seg
% |
Eos
% |
Baso
% |
Mono
% |
Lym
% |
|
911008 |
3.82 |
5.01 |
14.3 |
42.7 |
85.2 |
140.0 |
88 |
0.8 |
0.5 |
3.1 |
7.6 |
2. Biochemistry and electrolytes
| |
T/D-Bil
mg/dL |
Alb
g/dL |
TP
g/dL |
AST
U/L |
ALT
U/L |
ALP
U/L |
GGT
U/L |
GLU
mg/dL |
| 911011 |
0.4/0.2 |
3.5 |
6.7 |
16 |
46 |
150 |
44 |
|
| |
LDH
U/L |
BUN
mg/dL |
Cre
mg/dL |
UA
mg/dL |
Na
mmol/L |
K
mmol/L |
Cl
mmol/L |
Ca
mmol/L |
| 911008 |
|
9.6 |
0.76 |
|
137 |
3.79 |
|
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At ED, the head CT showed no
definite abnormality. Lumbar puncture was performed that
showed a very high opening pressure (>600 mmH2
O) and positive India ink smear in the
CSF. The CSF cell count was 0 /μL,
glucose 41 mg/dL and the total
protein 50.7 mg/dL. Following the diagnosis of
cryptococcal meningitis, amphotericin B and fluconazole were prescribed. Mannitol was given to
relieve increased intracranial pressure. MRI of the head disclosed
leptomeningeal process without space-occupying lesions.Anti- HIV antibody was positive.
Blood and CSF cultures performed
at ED subsequently yielded Cryptococcus
neoformans. CSF cryptococcal antigen titer was 1,024.
Anti-HIV antibody was tested positive, and HIV infection was
further confirmed by Western blot. His CD4+ count was 18/mm3
. Amphotericin-B
(50 mg qd) was continued for 30 days and switched
to fluconazole (400 mg qd) because of impairment
of renal function. Repeat lumbar puncture
(about three times a week) was performed
because of persistently high ICP. A lumbar drainage tube was
inserted for large-volume drainage of CSF in order to
control IICP. The procedure was complicated with CSF leakage, and repeat
lumbar puncture was performed.
His headache and diplopia
improved gradually. Antiretroviral therapy was started with
zidovudine, lamivudine and abacavir. Fluconazole was changed
to oral 200 mg qd after completion of an 8-week course. The
latest lumbar puncture before his discharge showed an open
pressure of 300 mmH2O and negative India ink smear.
 病案分析
本病患原本身體健康，在就診前一個月來，逐漸出現慢性的頭痛、嘔吐、發燒等病症。患者並無慢性耳鼻喉部位疾患；而且，病程逐日惡化。由這些表現，我們必須高度懷疑病患可能發生了腦壓上升、慢性腦膜腦炎、顱內腫瘤、或是顱內血管的病變。因此，電腦斷層或核磁共振的檢查，有助於鑑別診斷。
在排除顱內腫瘤或血管異常之後，對於這位年輕病患，我們必須考慮慢性腦膜炎的可能性。顱內或顱底膿瘍也可藉核磁共震或斷層排除慢性感染所致的腦膜炎。在台灣地區的流行病學看來，以結核菌和隱球菌（Cryptococcus
neoformans）所致的最為常見。但是，要分別其病因和病原，必須倚賴腦脊液檢驗。腦脊髓液的常規檢查，包括：細胞計數、分類、葡萄糖和蛋白質含量等，都能做為病因判斷的參考，至於病原種類，則有賴染色和微生物培養。染色中最重要的，包括：格蘭氏（Gram
stain）、抗酸染色（acid-fast stain）和India ink smear等。India ink
染色是診斷隱球菌腦膜炎最重要的方法之一，微生物培養能彌補染色的缺憾，惟所需時間較長，而且容易受經驗投予的抗生素影響，造成敏感度下降。要診斷隱球菌腦膜炎的另一利器是抗原檢驗（cryptococcal
antigen），這項檢驗可適用於血液、脊髓液和其他體液，它具有很高的敏感度和特異性，是診斷腦膜炎不可忘記的檢驗之一。
隱球菌藉由呼吸道進入肺部，可能造成肺部感染的病灶。肺部X光的變化，相當多樣化，可以從正常、間質性（interstitial
pneumonitis）、實質化（consolidation），到肋膜積水或開洞（cavitation）。由肺部擴展到血液，而後全身性感染，包括皮膚、淋巴腫，攝護腺、肝、脾等，和神經系統的感染。神經系統的感染，主要是腦膜炎，部分可能造成腦瘤或膿瘍般的變化。腦膜炎的特徵，往往是漸進惡化的頭痛和顱神經（cranial
nerves）的障礙，特別是第三、六、和八對顱神經。因此，患者容易出現複視和聽覺、平衡等障礙。另外，由於感染後造成腦脊髓液的吸收，受到影響，造成腦壓逐漸增加，因此，病患往往以頭痛、嘔吐表現。持續性的腦壓高，也會造成視神經乳突浮腫（papilledema）和視力障礙，甚至失明等。
隱球菌腦膜炎好發於T細胞功能障礙或數目不足的病患。這些包括：淋巴腫瘤、長期接受類固存醇等免疫抑制劑者、器官移植者，愛滋病患等。因此，針對原先健康的年輕人，發生了隱球菌腦膜炎，應檢查是否有上述的疾病，並特別是愛滋病。另外，和其他疾病相較，愛滋病患者可能更容易在併有腦模炎時，發生隱球菌血症。
治療隱球菌腦膜炎，必須投予適當的抗黴菌藥物與降低腦壓，雙管齊下，前者是以amphotericin B
(0.7 mg/kg/d)為首選藥物，在治療2-3周後，改成fluconazole
(6
mg/kg/d)。而降低腦壓的部分，則必須積極地施行脊椎穿刺或引流脊髓液，以降低腦壓。
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Case Discussion
繼續教育考題