a splitting headache…

the case.

39 year old female presents to your Emergency Department with a four day history of a gradually worsening headache. Whilst she has a past history of migraines, this headache is much more severe and of different character to any migraine she has had previously.

Her husband has bought her in with the concern that she isn’t as ‘alert’ as normal and she ‘isn’t behaving quite right’. The patient continually requests that you “take this splitting headache away!”

She takes regular triptans for her migraines & also has a contraceptive vaginal ring in situ. She has no known allergies.

On examination she is slightly drowsy, has difficulty following commands & is unable to form complete sentences. Her observations are as follows; P 110, BP 140/88, afebrile, SaO2 98% (RA). Cardiorespiratory examination is unremarkable. She has no focal neurological deficits, specifically unremarkable cranial nerves & full limb strength with intact reflexes and sensation. Her gait is not assessed because of her drowsiness.

[DDET What are your differential diagnoses in this case ??]

• Space occupying lesion [tumour, abscess, other…]
• Meningoencephalitis [viral vs bacterial vs other…]
• Subarachnoid haemorrhage or other intracranial haemorrhage [extradural, subdural, intraparenchymal…]
• Primary headache
• Carotid or vertebral artery dissection
• Vasculitis
• Endocrine or metabolic [less likely…]

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[DDET What are you doing to do next ??]

Basic laboratory investigations are unremarkable.

• BSL 7.2 mmol/L
• FBC normal
• Na 142 / K 4.3 / Ur 8.4 / Creat 76.
• CRP 21

Given the atypical nature of her headache and her altered mental state, you decide that she needs CNS imaging & send her for a CT…

[DDET Her non-contrast CTB…]

Non-contrast (axial) CT brain.

Non-contrast (coronal) CT brain.

[DDET The report…]

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[DDET the case continues…]

Upon returning from the radiology department, our patient has had an obvious deterioration in her neurological state. She is now obtunded with fluctuating periods of agitation.

Within minutes she has a generalised tonic-clonic seizure !!

Despite several doses of midazolam she continues to have short-lived seizure activity and requires intubation for airway protection and optimisation of ventilation.

With her airway secure, she returns to CT for further advanced imaging…

[DDET Here is her CT-venogram…]

CT-Venogram (axial).

CT-Venogram (coronal).

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[DDET CT report…]

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[DDET The diagnosis ?]

CEREBRAL VENOUS THROMBOSIS.

Thrombosis of the dural sinus and/or cerebral veins (CVT) is an uncommon form of stroke, usually affecting young individuals. Despite advances in the recognition of CVT in recent years, diagnosis and management can be difficult because of the diversity of underlying risk factors and the absence of a uniform treatment approach.

It represents ~0.5-1% of all strokes.

• 78% occur in patients < 50 years
• 34% will have an inherited or acquired prothrombotic condition

RISK FACTORS.

• Thrombophilias
  • Antithrombin III, Protein C & S deficiencies
  • Antiphospholipid & anticardiolipin antibodies
  • Factor V Leiden
  • Hyperhomocysteinaemia
• Pregnancy & post-partum period (~6-8 weeks)
• Oral contraceptive use
• Malignancy
  • Local affects
  • Hypercoagulable state
  • Medications (eg. Tamoxifen)
• Infection
  • Para-meningeal infections (ear, sinuses, dental, head & neck)
• Dehydration
• Substance abuse especially ecstasy
• Haematologic
  • Nephrotic syndrome, polycythaemia, thrombocytosis, Fe-deficiency
• Mechanical
  • Head trauma
  • Neurosurgery
  • Lumbar puncture
• Systemic diseases
  • SLE
  • Thyroid disease
  • Inflammatory bowel disease
  • Sarcoidosis

CLINICAL FEATURES.

Two major categories of clinical findings resulting from;

1. Increased intracranial pressure (2* to impaired venous drainage)
2. Focal brain injury from venous ischaemia/infarction or haemorrhage.

Patients typically present with a combination of these features.

1. Headache is the most common symptom in CVT (~90%).
   • Typically diffuse and progresses in severity over days to weeks
   • Can be sudden & severe (“thunderclap”) or migraine-like.
   • Isolated headache (without neurology or papilloedema) occurs in ~25% of cases.
2. Altered consciousness
3. Altered vision
   • 6th nerve palsy
   • Cavernous sinus involvement
4. Nausea & vomiting
5. Seizures (focal or generalised, ~40% of cases)

Clinical features are often dependent upon the location of the thrombus (see table below).

INVESTIGATIONS.

Bloods:

• Routinely: FBC, biochemistry & baseline coagulation profile
• Screening for potential prothrombotic conditions may have a role (but won’t help you acutely…)

Lumbar puncture:

• There are no specific CSF abnormalities in CVT.
• Opening pressure is elevated in >80% of cases.
• Elevated cell count & protein is also often seen.

D-dimer:

• A normal D-dimer may be considered to help identify patients with low probability for CVT.
• However, a normal D-dimer should not preclude further evaluation in patients with high-suspicion for CVT.
• Evidence limited to small prospective data (~400 patients)

IMAGING.

CT:

• Non-contrast CT scans are abnormal in only ~30% of cases.
• The primary abnormality on a non-contrast CTB is hyperdensity of a cortical vein or dural sinus.

• Thrombosis of the posterior part of the superior sagittal sinus may result in a dense (or filled) delta sign (see below).

• An ischaemic lesion that crosses usual arterial boundaries (or within proximity to a venous sinus) is suggestive of sinus thrombosis.
• Intracerebral haemorrhage occurs in up to 30-40% of patients with CVT. They often have prodromal headache or bilateral parenchymal abnormalities.

CT Venography:

• This may demonstrate a filling defect within the cerebral veins or sinuses known as the empty delta sign (see below).

• A rapid & reliable method of diagnosing CVT
• More useful in subacute & chronic disease states.
• Equivalent to MR-venography.

MRI + MR-Venography:

• More sensitive than CT at each stage after thrombosis.
• Findings are variable depending on the age of the thrombus.

MANAGEMENT.

(1) Admit to a Stroke Unit.

(2) Anticoagulation.

• Aim: prevent thrombus extension, facilitate recanalisation & prevent DVT/PE.
• Initially: 
  • Unfractionated heparin vs Low-molecular weight heparin
  • No data to support one over the other for Mx of CVT.
• Longer term:
  • Vitamin-K antagonists
  • Aiming for INR 2.0 – 3.0 for 3-6 months in most cases.
• For advanced interventions – see below.

(3) Seek + Treat Precipitating Causes.

• This includes bacterial infection (mastoiditis, meningitis etc) with management focusing on antibiotic therapy & surgical drainage of purulent collections.
• If hormonal therapy if thought to be the culprit; remove the source if able.
• Thrombophilia screening.

(4) Detect + Correct Complications.

• Raised intracranial pressure + Hydrocephalus:
  • Consider this with increasing visual symptoms (or deteriorating visual acuity)
  • Management may include medical therapy (eg. acetazolamide), lumbar puncture, optic nerve decompression or shunts.
  • Decompressive craniectomy may be required in the setting of neurological deterioration due to severe mass effect or intracranial haemorrhage refractory to medical therapy.
• Seizures:
  • Occur in up to 37% of adults (& ~50% of children) with CVT.
  • Anti-epileptic drugs are recommended following a single seizure (without parenchymal lesions).

(5) Advanced Interventions.

• Fibrinolytic therapy.
  • 9-13% of patients w/ CVT have poor outcomes despite anticoagulation.
  • Recanalisation rates may be higher with thrombolysis, however this is reserved for cases of ongoing deterioration despite anticoagulation (or with increasing ICPs).
• Direct catheter thrombolysis.
  • One small systematic review (169 patients) showed possible benefit of localised thrombolysis in severe CVT.
  • Carries a higher rate (17%) of intracerebral haemorrhage.
• Mechanical Thrombectomy/Thrombolysis.
  • Various devices available; evidence is largely anecdotal.
• Decompressive craniectomy.
  • Reserved for cases of refractory intracranial hypertension.

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[DDET Case conclusion]

With her CT demonstrating extensive sinus thrombosis, our patient is commenced on a heparin infusion before heading to Intensive Care for ongoing management.

Following extensive thrombophilia screening it is thought that her contraceptive ring was the culprit.

Despite having a rocky inpatient course she is eventually discharged home without neurological deficit with ongoing anticoagulation (warfarin) and levetiracetam for seizure control.

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[DDET References]

1. Saposnik, G., et al. Diagnosis and management of cerebral venous thrombosis: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2011; 42: 1158-1192 doi:10.1161/STR.0b013e31820a8364
2. Piazza, G. Cerebral venous thrombosis. Circulation, 125(13), 1704–1709. doi:10.1161/CIRCULATIONAHA.111.067835
3. Dural venous sinus thrombosis – Radiopaedia.org

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