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Inflammatory reaction after subarachnoid haemorrhage

Pathogen:None
Cause:Mostly the rupture of an intracranial aneurysm
Geographical range:Worldwide, predominantly in wealthy countries
Incidence:Approximately 100,000 per year

Case history

A 57-year-old woman suddenly experienced a severe headache. She was also disoriented and her neck was a bit stiff, so she went to the emergency department. On account of her symptoms, the physician suspected that the woman had suffered a life-threatening subarachnoid haemorrhage (SAH) and he immediately ordered a computed tomography (CT) scan. The CT scan results were negative, but the neuroradiologist still strongly suspected recent bleeding in the brain. A lumbar puncture was thus performed and cerebrospinal fluid (CSF) sent to the laboratory to investigate a possible subarachnoid haemorrhagic event.

Subarachnoid haemorrhage pathophysiology and diagnostics

A subarachnoid haemorrhage (SAH) is bleeding into the subarachnoid space – the area between the arachnoid membrane and the pia mater surrounding the brain. In most cases, SAH occurs spontaneously due to a ruptured cerebral aneurysm – An enlarged weakness in the wall of one of the arteries in the brain. They are usually located in the circle of Willis and its branches. SAH may also result from head injury, arteriovenous malformations, disorders of the blood vessels in the spinal cord and bleeding caused by various tumours (1). Furthermore, SAH may be triggered by cocaine abuse, sickle cell anaemia and (rarely) problems with blood clotting due to anticoagulant therapy.

About 10% of people admitted to the emergency department with a thunderclap (i.e. severe and sudden-onset) headache have suffered an SAH. Other possible causes considered for differential diagnosis are meningitis, migraine, cerebral venous sinus thrombosis and intracerebral haemorrhage (2). The misdiagnosis can sometimes lead to a delay in performing a CT scan, which may lead to a worse outcome (3). In some cases, the headache resolves itself and no other symptoms are present. This type of headache is referred to as a sentinel headache because it is presumed to result from a small “warning” leak from an aneurysm. A sentinel headache still warrants proper investigations with a CT scan and lumbar puncture since further bleeding may occur in the following weeks (4).

The diagnosis of a subarachnoid haemorrhage typically results from a strong clinical suspicion combined with confirmation (CT scan without contrast). CT scans are very sensitive in the first six hours after the onset of bleeding (close to 100%). However, the sensitivity decreases as time progresses: sensitivity is 93% within 24 hours of onset, 80% after 3 days, and 50% after 1 week (5). A lumbar puncture followed by cerebrospinal fluid analysis is generally regarded as mandatory in people with suspected SAH and negative CT scans (1). Although an elevated number of red blood cells in the CSF suggests a subarachnoid haemorrhage, damage to a small blood vessel during the lumbar puncture procedure (known as a “traumatic tap”) has to be excluded as the cause. The CSF sample is also often examined for xanthochromia – the yellow discolouration of centrifuged fluid determined by spectrophotometry. Xanthochromia remains a reliable way to detect older SAH events several days after the onset of the headache.

Laboratory results

 

Case interpretation

The XN high-sensitivity research mode for CSF revealed a severe leukocytosis (870 WBC/µL) in the WDF scattergram with high relative numbers of neutrophils (NEUT = 87.2%) and monocytes (MONO = 6.0%). The WDF scattergram also revealed high cell counts in those areas where activated monocytes and various macrophages were detected, when present (yellow).

Apart from the very high WBC count in this CSF sample, the RBC count from the RET scattergram showed a clearly pathological value (RBC = 362,300/µL). A high RBC count detected in the CSF may be caused either by a haemorrhage or by RBC contamination due to a traumatic tap. It is often difficult to differentiate between these two possible causes without further examination of the CSF, for example through the detection of xanthochromia or ferritin level measurements. In the case of this 57-year-old woman, the combination of a high RBC count and the high number of activated monocytes (erythrophages and siderophages) in the WDF channel clearly indicated a haemorrhage of an older origin. Therefore, a traumatic tap could be ruled out as a possible cause of the high RBC count in this sample. The diagnosis of subarachnoid haemorrhage was subsequently confirmed by the morphological review of a cytospin smear, where both erythrophages and siderophages were present. Further confirmation came from spectrophotometrical detection of xanthochromia in the cell-free fraction of the CSF.

References

  1. van Gijn J, Kerr RS, Rinkel GJ (2007): Subarachnoid haemorrhage. Lancet. Jan 27;369(9558):306-18.
  2. Longmore M, Wilkinson I, Turmezei T, Cheung CK (2007): Oxford Handbook of Clinical Medicine, 7th edition. Oxford University Press. p. 841. ISBN 0-19-856837-1.
  3. Kowalski RG, Claassen J, Kreiter KT, Bates JE, Ostapkovich ND, Connolly ES, Mayer SA (2004): Initial misdiagnosis and outcome after subarachnoid hemorrhage. JAMA. Feb 18;291(7):866-9.
  4. Suarez JI, Tarr RW, Selman WR (2006): Aneurysmal subarachnoid hemorrhage. N Engl J Med. Jan 26;354(4):387-96.
  5. Perry JJ, Stiell IG, Sivilotti ML, Bullard MJ, Emond M, Symington C, Sutherland J, Worster A, Hohl C, Lee JS, Eisenhauer MA, Mortensen M, Mackey D, Pauls M, Lesiuk H, Wells GA (2011): BMJ. Jul 18;343:d4277.

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