Headache in adults

Pathophysiology

• Structures in head capable of causing pain
  • Extracranial skin, mucosae, blood vessels, nerves, muscles, fascia
  • Main arteries at base of skull
  • Great venous sinuses
  • Basal dura and dural arteries
• Pathological processes that lead to headache
  • Tension: Contraction of muscles of head/neck
  • Traction: Stretching of intracranial structures due to mass effect. Typically constant.
  • Vascular: Dilatation/distension. Typically throbbing
  • Inflammation: Involves dura at base of skull or nerves or soft tissues of head/neck

Introduction

• 4% of presentations are due to high-risk causes 
• 10-14% of thunderclap headaches are from high-risk causes

Features associated with high-risk causes

• Age >50 with new or worsening headache
• Sudden onset
• Onset during exertion – SAH or arterial dissection
• Onset with valsalva – intracranial abnormality
• Headache quality – change in severity, pattern, frequency, quality or intensity (workup as if first presentation)
• Fever – absence does not rule out infectious cause however (esp. if elderly or immunosuppressed)
• Medication – Anticoagulants, antiplatelets, recent antibiotics, chronic steroid use or immunosuppressants (eculizumab increases risk of meningococcal disease)
• Chronic use of analgesics/anti-inflammatories may result in medication overuse headache/withdrawal/rebound headache
  • Use >10 times per month. Notable for ergots, triptans and opioids
• Prior headache history may obviate need for extensive workup
• Substance use
  • Cocaine, amphetamines increases risk of ICH and reversible cerebral vasoconstriction syndrome
  • Alcohol abuse risks ICH, trauma
• FHx
  • Aneurysm or sudden death in first-degree relative (3-5x risk)
  • Personal or FHx of autosomal dominant polycystic kidney disease
  • Migraine in first-degree relative increases risk of migraine 2-4x
• Associated conditions
  • Pregnancy/post-partum, SLE, Behcet’s, vasculitis, sarcoidosis, cancer
• Vital signs
  • Fever
    • Headache seen in 60% of URTI
    • Persistent of headache once temperature normalised  suggests further evaluation for CNS infection
    • Fever + neck stiffness + ALOC = classic triad of meningitis
    • 95% of meningitis patients present with at least 2/4 of classic triad + headache
  • Severe HTN
    • May be cause of headache (PRES, RCVS, hypertensive emergency) or a sign of ICH
• Meningismus
• ENT examination for sinusitis +- intracranial extension
• Temporal artery
• Eye – acute angle closure glaucoma, scleritis, endophthalmitis
• Papilloedema seen in raised ICP – need CT before LP (benign ICH or mass lesion)
• Neurological examination crucial

Causes of thunderclap headache

• Haemorrhage
  • Intracranial haemorrhage
  • Sentinel aneurysmal haemorrhage
  • Spontaneous intracerebral haemorrhage
• Vascular
  • Carotid or vertebrobasilar dissection
  • Reversible cerebral vasoconstriction syndrome (RCVS)
  • Cerebral venous thrombosis
  • Posterior Reversible Encephalopathy Syndrome (PRES)
  • Pre-eclampsia
  • Acute posterior circulation stroke
  • Giant cell arteritis
  • Transient global amnesia
• Other
  • Coital headache
  • Ice-pick headache
  • Valsalva-associated headache
  • Spontaneous intracranial HYPOtension
  • Acute hydrocephalus
  • Pituitary apoplexy
  • Meningitis or encephalitis

Clinical features suggestive of migraine

• Prior history of migraine
• Younger age
• Multiple prior episodes
• Family history
• Aura (before or during)
• History of motion sickness
• Moderate/severe intensity
• Unilateral, throbbing
• Nausea/vomiting
• Photophobia/phonophobia
• Lasts hours

Clinical features of cluster headache

• 5 attacks that are:
  • Severe
  • Unilateral
  • Last 15-180min (without treatment)
  • Circadian/circannual pattern
• Associated ipsilateral (at least one):
  • Lacrimation
  • Conjunctival injection
  • Nasal congestion/rhinorrhoea
  • Ptosis/miosis
  • Oedema of eyelid/face
  • Sweating of forehead/face

Lumbar puncture

• Both diagnostic and therapeutic
• If suspicious of space occupying lesion, must CT first
• Cumulative evidence suggests if no history of immunosuppression, normal sensorium and no focal neurology – safe for LP without prior CT
• Risk of an abnormal CT (not necessarily herniation) in meningitis increased by:
  • Deteriorating or altered GCS (<=11)
  • Brainstem signs (pupillary changes, abnormal breathing, posturing)
  • Focal neurological deficit
  • Hx of pre-existing neurological disorder
  • Hx of seizure
  • Immunocompromised state

Meningitis

• Need high index of suspicion
• Always consider if immunosuppressed (HIV, cancer, chemotherapy, chronic steroids) as may have more insidious onset e.g. cryptococcus
• Administer antibiotics +- steroids immediately if any delay in LP

Subarachnoid haemorrhage

• SAH from intracranial aneurysm rupture carries 50% 30-day mortality rate
• 50% of survivors have some degree of neurological impairment
• 1% of patients presenting to ED have SAH
• 10-14% of thunderclap presentations (Cameron says 25% of sudden severe headache)
• 50% have sentinel bleed in hours to weeks prior
• Acute onset severe headache is SAH until proven otherwise
  • Typically crescendo within minutes and resolves over days
• Headaches associated with LOC, seizure, diplopia, focal neurology all raise suspicion
• 20-33% present after developing symptoms during exercise, intercourse, defecation
• 75% due to aneurysmal rupture (85% in Cameron); 10% perimesencephalic non-aneurysmal and 5% from rare causes
• 20% of patients with one aneurysm have another one making identification of the first one important
• 2% of family members of patients with SAH will develop the same disease
  • Risk rises with increased number of family members and ADPKD
• Early diagnosis is imperative as early occlusion of aneurysm shows reduced early re-bleeding and improved outcomes
• >5-10mm aneurysms more commonly rupture than those <5mm
• In the absence of trauma, subhyaline retinal haemorrhage is pathognomonic of SAH (Terson syndrome)
• Missed diagnosis – Those that are misdiagnosed on initial presentation to ED have poorer outcomes
• Misdiagnosis associated with normal LOC (50% of patients with SAH), smaller size of haemorrhage
• Complications of missed diagnosis include repeat haemorrhage, obstructive hydrocephalus
• Symptomatic improvement with analgesics does not rule out sinister cause for headache
• 50% present in coma and 2/3 with impaired LOC on ED arrival
• Meningism in 75% of patients but may develop over hours
• Focal neurological signs in 25% of patients secondary to associated intracranial haemorrhage, cerebral vasospasm, local compression of cranial nerve by aneurysm (e.g. oculomotor nerve palsy by posterior communicating artery aneurysm or bilateral lower limb weakness due to anterior communicating artery aneurysm) or raised ICP (6^th nerve palsy)
• Systemic features include severe hypertension, hypoxia (neurogenic pulmonary oedema) and ECG changes (may mimic STEMI)
• Small proportion present in cardiac arrest. 50% of survivors regain independent function so resuscitation is crucial

• Rare causes (5%)
  • Rupture of mycotic aneurysm
  • Intracranial arterial dissection
  • AV malformation
  • Vasculitis
  • Central venous thrombosis
  • Bleeding diatheses
  • Tumours
  • Drugs (cocaine, amphetamines, anticoagulants)

• Aneurysms
  • Not congenital
  • Develop over lifetime
  • 2.3% prevalence in population and proportion increases with age
  • Paradoxically, most aneurysms that rupture are small (as most are small) but risk does increase with size
  • Posterior rupture more readily than anterior if comparable size
• Non-aneurysmal perimesencephalic haemorrhage
  • Classic distribution of blood in cisterns around midbrain with normal angiographic studies

• Risk factors (Cameron)
  • Non-modifiable
    • Hx of previous aneurysmal SAH, FHx of first-degree relative with SAH, inherited connective tissue disorder (PKD, neurofibromatosis), sickle cell disease and alpha-1 AT disease
  • Modifiable
    • Cigarette smoking, HTN, sympathomimetic use, alcohol
• Risk factors (Tintinalli)
  • HTN
  • Smoking
  • Alcohol
  • Polycystic kidney disease
  • FHx of SAH
  • Coarctation of the aorta
  • Marfan syndrome
  • Ehlers-Danlos type IV
  • Alpha-1 AT deficiency

Diagnosis

• Pathway
  • Non-contrast CT head
    • Negative within 6 hours of onset -> Rule out SAH
    • Positive -> Rule in SAH -> Carry on to CT-A
    • Negative >6 hours from onset ->
      • Need to then decide either LP at 12 hours for xanthochromia OR CT-A (see below)
• Imaging
  • Non-contrast CT head
    • Sensitivity approaches 100% within 6 hours of onset
    • Sensitivity 98% within 6-12 hours of symptom onset
    • 91-93% at 24 hours
    • 50% at 1 week
    • Can help to identify site of haemorrhage in anterior or AComm arteries
    • MRI not as sensitive
  • CTA/MRA
    • Options after a negative head CT
    • 2/116 patients had an aneurysm on CTA after negative CT head and LP
    • The probability of excluding SAH after a negative CT/CTA is 99.4%
    • Importantly, may detect incidental aneurysms (2-6% background rate)

• Lumbar puncture
  • Most authorities recommend this after negative CT
  • 3-5% of patients with SAH will have normal head CT (this is overall and perhaps a negative scan within 6 hours is sufficienct – depends on pre-test probability)
  • Another advantage is identification of alternative diagnosis (meningitis, IIH or cerebral venous thrombosis)
  • Xanthochromia
    • Visual inspection or spectrophotometry (superior sensitivity but only 75% specificity – therefore generates false positives). Visual inspection not sensitive enough though.
    • Takes 12 hours to develop xanthochromia and is present in all patients with SAH from 12 hours to 2 weeks
    • Sample exposure to sunlight reduces level of xanthochromia
    • Delayed testing of sample increases xanthochromia in traumatic tap via oxyhaemoglobin (false positives)
  • RBC count
    • RBC <100 in final tube effectively rules out SAH
    • RBC > 10000 in final tube increases OR of SAH by 6

• In general:
  • Normal head CT, no xanthochromia and <5×10^6 RBC/L reliably excludes SAH
  • Normal head CT with positive xanthochromia = SAH
  • Normal head CT, negative xanthochromia and >5×10^6 RBC/L = maybe SAH (precise cut-off not known). Needs CTA

Grading scales

• Hunt and Hess
• WFNS
• Fisher scale
  • I – No blood
  • II – Diffuse deposition of SAH without clots or layers >1mm
  • III – Localised clots and/or vertical layers of blood >1mm
  • IV – Diffuse or no subarachnoid blood but intracerebral or intraventricular clots
  • Predicts likelihood of vasospasm

Complications

• Early
  • Re-bleeding: 15% within hours and overall 40% within first 4 weeks. 60% mortality rate and 50% of survivors remain disabled. Prevented by good BP control
  • Subdural haematoma or large intracerebral haematoma: May require drainage
  • Global cerebral ischaemia: Likely secondary to marked rise in ICP at time of aneurysm rupture
  • Cerebral vasospasm: Clinically significant spasm occurs in 20% of SAH and is major cause of death and morbidity Tends to occur day 3-15 with peak at day 6-8. Should be suspected in any drop in GCS or new neurological deficit. 
  • Hydrocephalus: 20% of patients. Can occur within 24 hours
  • Seizures
  • SIADH or cerebral salt wasting
  • Hyperglycaemia and hyperthermia
  • Medical complications: Neurogenic pulmonary oedema, cardiac arrhythmia, sepsis, VTE and respiratory failure
• Late complications
  • Late re-bleeding: From new aneurysm or re-growth of treated aneurysm. 1.3% in 4 years for coiling and 2-3% in 10 years for clipping
  • Anosmia in 30%
  • Epilepsy in 5-7%
  • Cognitive deficits and personality change in 60%
  • Delayed cerebral ischaemia related to hyperglycaemia and poor temperature control
• A drop in GCS by 1 point can herald complications

Blood pressure control

• If known, maintain pre-morbid blood pressure with sedation/analgesia
• Antihypertensive therapy should be reserved for severe HTN (MAP >130) or evidence of progressive end-organ dysfunction
• Titratable labetalol or nicardipine infusions are preferred
  • Labetalol 10mg IV over 1-2min then infusion 2-8mg/min
• Avoid nitroprusside and GTN as increase cerebral blood volume and intracranial pressure
• Analgesics and antiemetics may also play a role in BP control
• Controversial targets but MAP <130 and SBP <160 is probably sufficient

Vasospasm

• Most common 2 days to 3 weeks after bleed
• Nimodipine 60mg PO q4h should be initiated within 96 hours unless contraindicated due to allergy, non-functioning GI tract or hepatic disease
• Maintain euglycaemia and normal temperature, sodium homeostasis, VTE prophylaxis (compression only initially) and treatment of hydrocephalus

Seizures

• 5-20% of patients suffer at least one seizure
• Routine use of long-acting phenytoin prophylaxis is associated with unfavourable function and cognitive outcomes
• Discuss prophylactic agents with neurosurgeons taking over care

Prevention of re-bleeding

• Obliteration of ruptured aneurysm should be performed as soon as possible to prevent re-bleeding, remove clot, reduce incidence of early complications and improve outcomes
• Endovascular occlusion (coiling)
  • Not suitable for all aneurysms
  • Better outcomes at 4 years than clipping but higher aneurysm recurrence rates and re-bleeding rates
• Surgical clipping (second-line)
  • Usually within 3 days (preferably within 24 hours)

Prevention of delayed cerebral ischaemia

• Nimodipine 60mg q4h PO for 3 weeks improves clinical outcome with relative RR of 18% and absolute RR of 5.1%
  • Should be commenced within 48 hours
• Treatment of vasospasm
  • Induced HTN is an option
  • If unresponsive to medical therapy, emergency cerebral angiography with intra-arterial vasodilator therapy or transluminal balloon angioplasty may be considered

Prognosis

• 40-60% mortality rate
• 1/3 of survivors have neurological deficit
• Most important prognostic factor is clinical condition at time of presentation
• Survival rates
  • Grade I – 70%
  • Grade II – 60%
  • Grade III – 50%
  • Grade IV – 40%
  • Grade V – 10%

Disposition and Follow-up

• Patients with normal head CT and CSF findings within 2 weeks of initial symptoms can be safely discharged from ED
  Consider consultation with neurosurgery if presents >2 weeks from onset of severe headache if initial workup is unremarkable as further vascular imaging may be warranted
  

Investigation of thunderclap headache after previous aneurysm treatment

• Differential includes alternative cause of headache (common after aneurysm treatment), bleed from original aneurysm (failed coiling/clipping), bleed from de novo aneurysm (new aneurysms are more common in those that have had one previously) or perimesencephalic haemorrhage
• It is crucial to identify failure of original therapy or de novo aneurysm formation
• Previous highly sensitive post-interventional/operative monitoring scans (e.g. MRA/DSA) will give some guide as to the likelihood of either of these events
  • For example, if recent monitoring scan showed secure aneurysm and no new aneurysms then likelihood of a change in this is low

CT-A vs. DSA for aneurysm detection

• CTA is 83-98% sensitive for identification of ruptured aneurysms in SAH as compared to DSA
  • Probably >97% for modern multidetector scanners
  • Aneurysms <3mm are not reliably identified (although more likely in modern multidetector scanners)
  • Although small aneurysms rupture less frequently, they are more common and therefore are more likely to be a cause in a confirmed SAH
  • This is why DSA should be performed if CT-A is negative for aneurysms in a confirmed SAH
  • In the case of a negative DSA, this should be repeated in several weeks due to the 14% risk of subsequent identification of an aneurysm (may have been in vasospasm or clotted on the original DSA)
  • There may be a situation where a classic perimesencephalic haemorrhage pattern combined with a negative CT-A is adequate for ruling out aneurysmal SAH but this should be in liaison with Neurosurgery
  • DSA also provides better resolution for interventional planning

Perimesencephalic subarachnoid haemorrhage

• Blood in the cisterns around the midbrain reflects perimesencephalic haemorrhage
• This accounts for about 10% of SAH and a majority of non-aneurysmal SAH
• Long-term follow-up suggests rebleeding is exceptional and life-expectancy is NOT altered

Intracerebral haemorrhage

Introduction

• Spontaneous ICH constitutes 8-11% of all strokes
• Twice as common as SAH
• 7-day mortality is 30%, 1 year mortality 55% and 10-year mortality 80%
• Of survivors, 80% have disability at one year
• Anticoagulation with warfarin is a significant risk factor with annual incidence of 0.3-0.6%
• Warfarin plays a role in 6-16% of all spontaneous ICH
• Risk of sICH doubles for each 0.5 increase in INR above 4.5
• Occurs in 3-9% of stroke thrombolysis patients
• Direct thrombin inhibitors seem to carry similar risk to warfarin

Risk factors

• Long-standing HTN
• Arteriovenous malformations
• Arterial aneurysm
• Anticoagulant therapy
• Sympathomimetic abuse
• Intracranial tumors
• Amyloid angiopathy in the elderly
• Current smoking

Causes

• Primary
  • Hypertensive vascular disease (85%)
    • Lipohyalinosis causes rupture of small penetrating vessels in the putamen, thalamus, upper brainstem and cerebellum
  • Amyloid angiopathy
    • Mostly seen in elderly patients with lobar haemorrhages
• Secondary
  • Ruptured cerebral aneurysm
  • AV malformation
  • Haemorrhage into underlying lesions
  • Drug toxicity from sympathomimetics
  • Anticoagulation/bleeding diatheses
  • Post-infarct haemorrhage

Presentation

• Most commonly hypertension-induced small vessel disease in basal ganglia, thalamus and cerebellum
• Berry aneurysms mostly around Circle of Willis, hence ICH found in that area
• Classic presentation is sudden onset neuro deficit, headache, collapse/transient LOC, vomiting, hypertension
• Headache usually precedes neurological deficits and is more insidious in onset compared to SAH
• CT and MRI equivalent in identifying ICH
  • CTA can identify underlying aneurysm/AVM/vasculitis

Prognosis

• 35-50% mortality with half in first 2 days + very high risk of disability
• 12-39% functionally independent at 12 months
• Poor prognostic factors
  • Age over 80
  • High NIHSS
  • GCS 3-4
  • Volume of blood >30mL
  • Infratentorial
  • Intraventricular extension of haemorrhage

• Hypertensive ICH
  • Bleeding usually in putamen, thalamus, pons or cerebellum (in decreasing order)
  • Cerebellar haemorrhage often presents with nausea, vomiting, truncal ataxia, gaze palsies and reduced LOC
  • Cerebellar haemorrhages often have precipitous decline and need urgent intervention

• Diagnosis
  • CT is optimal for identifying extension of haemorrhage into ventricles
  • MRI superior for demonstrating underlying structural lesions
  • Non-contrast CT is first-line. Addition of contrast may identify masses or aneurysms.
  • Cerebral angiography may be suitable for stable patients who do not require urgent surgery, particularly in:
    • Those in whom no obvious source of bleeding is found
    • Under 45 without hypertension

• Treatment
  • Close monitoring, euglycaemia, TTM
  • Anticonvulsants if seizures occur
  • Treatment of raised ICP
  • Blood pressure control
    • INTERACT2 study showed no reduction in death or severe disability in the rapid reduction in BP group (<1 hour to <140mmHg) but did show better functional outcomes
  • Reversal of coagulopathy (if present)

• Coagulopathy reversal
  • Unfractionated heparin – Protamine 1mg/100U of heparin adjusted based on time of last heparin dose (max 50mg – add up last 3 hours of dosing)
  • Warfarin – Reverse nomatter what the INR. FFP 300mL + 50U/kg prothrombinex + vitamin K 10mg IV
  • Aspirin and ADP receptor agonists
    • Platelets likely result in increased rate of death and disability (PATCH)
    • Desmopressin in consultation with neurosurgery and haematology
      • Frontera et al. (2016) in Neurocrit. Care recommended this + platelets if undergoing neurosurgical procedure or desmopressin alone if no neurosurgical procedure planned
  • LMWH
    • If dosed within last 8 hours; 1mg protamine/1mg LMWH Up to 50mg
    • If dosed 8-12 hours age – 0.5mg protamine/1mg LMWH up to 50mg
    • If dosed >12 hours ago – No protamine
  • Dabigatran – 5g idarucizumab (Praxbind)
  • Apixaban – Prothrombinex 50U/kg
  • Rivaroxaban – Prothrombinex 50U/kg
  • Consider activated charcoal if airway controlled 50g OG if oral anticoagulant

• Post-thrombolysis
  • Stop lysis infusion
  • FFP 2U q6h
  • Cryoprecipitate 10U
  • Tranexamic acid 1g IV
  • Platelets 1 bag
  • DDAVP 0.3mcg/kg
  • Protamine for any heparin administered

• Blood pressure control
  • BP >200/>150
    • Consider aggressive reduction with continuous IV labetalol infusion to <140 systolic or drop by 10-15%
  • BP >180/>130 and suspicion of raised ICP
    • Consider ICP monitoring and continuous IV labetalol to maintain CPP >60-80mmHg
  • BP >180/>130 without suspicion of raised ICP
    • Consider modest MAP target <110 or BP <160/90 using IV labetalol infusion
  • INTERACT trial of intensive BP reduction within 6 hours showed reduction in haematoma growth
  • INTERACT 2
    • No significant reduction in primary outcome of death or severe disability but ordinal analysis showed improved functional outcomes with intensive lowering of SBP <140mmHg (current AHA/ASA guideline)

• Anticonvulsant prophylaxis is common but not mandatory
• Reverse any coagulopathy
  • Platelets not recommended if on antiplatelets (PATCH trial) but desmopressin may be of benefit

• Surgical drainage
  • High-level evidence of benefit in supratentorial haemorrhages is lacking
    • Strongly encouraged in those with lobar clots within 1cm of surface
    • Best if:
      • Refractory intracranial HTN
      • Non-dominant hemisphere
      • Not obtunded (poor prognosis regardless)
      • Deteriorating
  • EVD’s indicated if hydrocephalus develops
  • Cerebellar haematomas need urgent drainage to prevent brainstem compression

Subdural haematoma and ICH

• In prospective trial of blunt head trauma, 12% of those on clopidogrel and 5% of those on warfarin had acute ICH on initial CT
• Risk of delayed ICH 0% in clopidogrel group and 4/687 in warfarin group
• Acute headache with vestibular symptoms = cerebellar haemorrhage until proven otherwise
  • Make up 10% of ICH and need prompt evacuation to prevent death/disability

Brain tumour

• Suggested by focal neurology, headache worse with Valsalva, headache waking from sleep, seizures, recent cancer diagnosis or mental status change
• Most patients do NOT have neurological findings at diagnosis
• MRI is the study of choice
• Non-contrast CT will rule out larger masses and associated oedema but cannot rule out small masses

Cerebral venous thrombosis

• Consider in new headaches with risk factors
  • Women
  • Peripartum
  • Recent surgery
  • Hypercoagulable states
  • COCP
• May present as progressive headache, thunderclap, seizures, stroke or coma. Can be benign through to severe on presentation
• Multiplex CT-A will usually show venous thrombosis or secondary signs i.e. convexal subarachnoid haemorrhage without dedicated venography
• If initial CT/MRI abnormal, focal neurology exists or ALOC – diagnosis confirmed by MR venogram
• Elevated LP opening pressure should raise suspicion
• LP can be safely performed in these patients
• CT venogram reported to be 95% sensitive

PRES

• Posterior reversible encephalopathy syndrome
• Aka Reversible posterior leukoencephalopathy syndrome (PRLS)
• Names are unsatisfactory as not always reversible, nor confined to white matter or posterior regions
• Described in the setting of hypertensive encephalopathy, eclampsia, cytotoxic and immunosuppressive drugs
• Typically involves subcortical white matter in posterior hemispheres
• Pathogenesis
  • Autoregulatory failure
  • Cerebral ischaemia from focal vasoconstriction
  • Endothelial dysfunction
• Severe persistent headache, altered consciousness, visual changes, seizures and encephalopathy with marked blood pressure rise
• Other focal neurological findings are rare
• Most common in those on immunosuppression or chemotherapy or ESRD
• Non-contrast CT
  • White matter oedema in both cerebral hemispheres is common
    • Calcarine and paramedian parts of occipital lobe are spared to distinguish from bilateral posterior cerebral infarctions
  • Cortex and basal ganglia may be involved
  • Distribution usually not confined to single vascular territory
• MRI
  • Symmetrical vasogenic oedema in occipital region (increased signal on T2-weighted images)
  • Hypo- or isointense signal on DWI (vs. hyperintense in top-of-basilar stroke)
• Complications
  • Ischaemia
  • ICH in up to 20%
• Follow-up imaging showing resolution confirms diagnosis
• DDx
  • Hypertensive encephalopathy (significant overlap and Rx of HTN is key in both)
  • Eclampsia
  • RCVS (usually thunderclap headache with less visual changes, seizures or MRI abnormalities and show vasoconstriction on vascular imaging – there is considerable overlap here)
  • Cerebral venous thrombosis
  • Autoimmune, paraneoplastic or infectious encephalitis
  • Acute demyelinating encephalomyelitis (ADEM) (usually post-infectious or post-vaccination; seizures are uncommon)
  • CNS lymphoma
  • Acute toxic leukoencephalopathy (heroin, CO, hydrocarbons, acute lead poisoning, cranial irradiation)
• Treatment
  • Manage HTN aggressively (SBP <140, DBP <105 within 2-6 hours with maximum initial drop <25% of total – UpToDate)
  • Treat seizures +- urgent EEG for possible non-convulsive status if ALOC
  • Cease immunosuppressive therapy
• Prognosis
  • Usually benign and vast majority reversible within days to weeks
  • Death and permanent disability do rarely occur
  • Recurrence is rare (<10%)

Reversible cerebral vasoconstriction syndrome (RCVS)

• Mimics subarachnoid haemorrahge
• One or more thunderclap headaches with diffuse cerebral vasospasm
  • The presence of multiple thunderclap headaches over days is almost 100% sensitive and specific for RCVS
• HTN is common but may be due to pain, disease itself or associated condition e.g. pregnancy/eclampsia, cocaine use
• Incidence greater in women and mostly >40yo
• Vasoconstrictive triggers
  • Pregnancy-related: Third trimester and postpartum, eclampsia and pre-eclampsia
  • Headache disorder: Migraine, primary thunderclap headache, benign headache with exertion, benign headache associated with sexual activity, primary headache associated with cough
  • Physiologic: High altitude, cold and heat exposure, reaction to grief
  • Substances: Sympathomimetics, serotonergic agents, immunosuppressants, immunomodulators, hormonal medications (oestrogen, ovarian stimulation, levonorgestrel), cocaine, ecstasy, amphetamines, marijuana, LSD
  • Procedure-related: Carotid artery, open neurosurgical procedures, tonsillectomy, dural puncture
• Often occurs with orgasm, physical exertion, acute emotional/stressful scenarios, Valsalva manoeuvres, bathing and/or swimming
• Often quite different to previous migraines described by patients with a history of this
• May also have seizure or focal neurological deficit owing to ischaemic stroke, ICH or reversible cerebral oedema
• Visual deficits are usually seen if concomitant RPLS/PRES
• Cerebral angiography shows multiple area of cerebral vasoconstriction, usually around circle of Willis
  • Described as strings on a sausage
• Rate of permanent neurological disability is 6-20%
• Initial imaging
  • May show non-aneurysmal SAH, ischaemic stroke or ICH
  • Non-contrast head CT
    • Most often normal on presentation (30-70%)
    • 75% eventually develop parenchymal lesions with ischaemic stroke or cortical surface non-aneurysmal subarachnoid haemrrhage followed by vasogenic oedema and parenchymal haemorrhage
    • Infarcts are often bilateral, symmetrical and located in watershed areas
• CT/MR angiography
  • May show smooth-tapered vasoconstriction around CoW with abnormally dilated downstream branches
  • May be normal early in course and often worth repeating scan in 3-5 days if high suspicion
• Treatment
  • Manage pain and seizures
  • BP management carries significant risk of relative hypoperfusion
  • Some patients may benefit from vasodilators and/or intra-arterial vasodilation if progressive course
• Prognosis
  • <20% have residual deficits
  • <5% of severe disability
  • Timecourse of symptoms is usually days to weeks with resolution in most
• Scoring system
  • Score of 5 or higher = 99% specificity and 90% sensitivity for RCVS
  • Score of 2 or lower = 100% specificity and 85% sensitivity for ruling out RCVS

Moyamoya

• Specific angiographic findings of unilateral or bilateral stenosis/occlusion of CoW arteries with prominent arterial collateral circulation (that looks like a puff of smoke)
• Seen predominantly in Japanese/Asian individuals
• Most commonly presents as ischaemic stroke/TIA
• Haemorrhagic complications of ischaemia are common

Temporal arteritis

• Incidence increases with age >50 (almost exclusive)
• Most common systemic vasculitis and most common vasculitis above age 50
• 1% lifetime risk for women and 0.5% for men
• 80% over 70yo
• 50% have PMR while 15% of PMR have GCA
• Aortic and other large vessel involvement is more common than previously thought but does have predilection for carotids and branches
  • Perhaps up to 50% of cases have aortic involvement in some fashion
• Headache + fatigue, fever, proximal weakness, jaw claudication (50%), TIA symptoms (esp. transient visual loss)
  • Do not NEED To have headache and in these patients jaw claudication may be predominant
• 3 of 5 criteria must be met (93% sensitivity; 91% specificity)
  • Age >50
  • New headache
  • Temporal artery abnormality (enlarged, tenderness, reduced pulsation)
  • ESR >50
  • Abnormal biopsy
• ESR <50 negative likelihood ratio of 0.2
• Sensitivity of unilateral temporal artery biopsy is 90%
• Begin Rx with methylprednisolone 1g IV then prednisolone 60mg daily to reduce visual impairment and stroke risk and refer to ophthal + rheumatology

Visual loss

• Transient monocular amaurosis fugax is most common
  • Usual partial visual field defect or temporary curtain
  • Can be harbinger of more severe/permanent visual loss
• Permanent partial or complete visual loss is seen in up to 20% of cases
• Within 1 week, other eye suffers vision loss in 25-50%
• If vision intact at time of steroid initiation, risk of loss if virtually abolished and prevents further deterioration

Large-vessel GCA

• Refers to involvement of aorta and proximal branches
• Up to 50% of GCA patients have involvement on CT-A/FDG-PET
• Typically younger, less likely to have headaches and may have arm claudication
• 10-20% show aortic aneurysms (esp. thoracic)
• 1-6% suffer aortic dissection/rupture

Migraine

• Usually start in childhood and peak around age 40
  • Rare to have first episode over 55yo
• Prevalence 5% in males and 15-17% in females
• Idiopathic recurring headache with attacks lasting 4-72 hours
• Typically unilateral, pulsating, moderate-sever intensity and aggravated by routine activity +- nausea, photophobia and phonophobia
• May have preceding aura: Visual disturbance, paraesthesia, diplopia, weakness
  • Develop over 5-20 minutes and last <60 minutes
• Chronic migraine = 5 or more migraine headache days per month for 3 months

Migraine classification

 – International Headache Society

• Migraine without aura
  • A – At least 5 attacks of B
  • B – Headache lasting 4-72 hours
  • C – At least 2 of:
    • Unilateral
    • Throbbing
    • Moderate to severe intensity
    • Aggravated by physical activity
  • D – At least 1 of:
    • Nausea/vomiting
    • Photophobia and phonophobia
  • E – Not attributable to any other cause

• Migraine with aura
  • A – At least 2 attacks of B
  • B – Aura of one of 6 forms
  • C – No other attributable cause
• Aura forms
  • Typical aura with migraine headache
  • Typical aura with non-migraine headache
  • Typical aura without headache
  • Familial hemiplegic migraine
  • Sporadic hemiplegic migraine
  • Basilar-type migraine

• Typical aura with migraine headache
  • A – At least 2 attacks fulfilling B-D
  • B – Aura with at least 1 of the following, but no motor weakness
    • Fully reversible visual symptoms
    • Fully reversible sensory symptoms
    • Fully reversible dysphasia
  • C – At least 2 of:
    • Homonymous visual &/or unilateral sensory symptoms
    • Aura develops gradually over >5 min
    • Symptoms <60 min
  • D – Headache begins during or within 60 minutes of aura
  • E – Not attributed to any other disorder

• Typical aura with migraine headache
  • Visual auras most common – Fortification spectra, zigzags, scotoma +- scintillating
  • Sensory changes next – Pins and needles, numbness
  • Speech disturbance least frequent
  • Can progress visual —> sensory —> speech

• Basilar type migraine
  • A – At least 2 attacks fulfilling B-D
  • B – Aura with at least 2 of the following without motor disturbance
    • Dysarthria
    • Vertigo
    • Tinnitus
    • Hyperacusis
    • Diplopia
    • Visual symptoms in both temporal and nasal fields both eyes
    • Ataxia
    • Reduced LOC
    • Simultaneous bilateral paraesthesia
  • C – At least one of the following
    • Aura symptom onset gradual over >5 min
    • Aura symptoms offset within 60 minutes
  • D – Headache within 60 minutes
  • E – Not attributable to another disorder

Migraine variants

• Ophthalmoplegic
  • Headache associated with paralysis of EOM +- Horner’s syndrome
  • Rare cause
• Abdominal
  • Recurrent abdominal pain with no other cause
• Hemiplegic
  • Stroke mimic
• Retinal
  • Recurrent retinal ischaemia leading to bilateral optic atrophy

Migraine pathophysiology

• Aura
  • Brief excitation followed by prolonged cortical spreading depression of regional blood flow due to glutamate release
• Brain stem disturbance
  • Serotonergic system changes lead to vascular phase
• Vascular phase
  • Epiphenomenon i.e. not primary cause of headache
  • Constriction and dilatation of intra- and extracranial vessels
• Trigeminal response
  • Nociceptive trigeminal vascular system activated
  • Release of vasoactive peptides i.e. serotonin —> substance P

Triggers

• Missing meals
• Sleep deprivation
• Prior to or during menstruation
• Stress
• SSRI/oestrogens/PPI

Sequence of events

• Prodrome —> Aura —> Headache —> Resolution
• Prodrome
  • 50-80% of cases usually within 1 hour but up to 24 hours prior
  • Osmophobia, photophobia, phonophobia
  • Yawning, drowsiness
  • Irritability
  • Thirst, hunger
  • Lacrimation

• Aura
  • 10-20% of cases
  • 90% of cases with aura have visual symptoms
• Headache
  • Unilateral in 60%
  • Median time to peak intensity is 60 minutes
  • Bilateral more common in children
  • Usually frontotemporal or occipital (occipital rare in children)
  • Classically throbbing (50%) but 30% of tension headaches are throbbing
  • 90% worse with movement

Diagnosis

• POUNDing
  • Pulsating
  • Duration 4-72 hours
  • Unilateral
  • Nausea
  • Disabling
• 4 criteria = +LR 24
• 3 criteria = +LR 3.5
• <3 criteria = +LR 0.41

Red flags

• 20% of SAH occur in those with history of migraine
• Sudden onset
• First episode >55yo
• Exertional or with intercourse
• Worst ever
• Different from usual pattern
• Subacute onset and worsening
• Reduced LOC, speech disturbance
• Fever
• Meningism
• Papilloedema

Migraine management (NICS guidelines)

• Initial therapy
  • First-line abortive therapy = triptans (80% past this by time get to ED)
  • Triptans contraindicated in IHD, uncontrolled HTN or concomitant ergot use
• Mild
  • Aspirin 900mg + Metoclopramide 10mg PO
• Moderate
  • Above 
  • Metoclopramide 10mg IM or Prochlorperazine 12.5mg IM or Sumatriptan 6mg SC 
• Severe/vomiting
  • Chlorpromazine (largactil – has M in it) 12.5-25mg IV in 1L N/saline over an hour OR
  • Prochlorperazine 12.5mg IV in 1L N/S over an hour OR
  • Sumatriptan 6mg SC
• >50% of patients have residual headache on d/c from ED and there is an increased rate of recurrence of headache within first 3 days of d/c
  • Recurrence rates reduced by 26% with dexamethasone IV 10mg
• Prescription for abortive agents is useful
• Migraine-specific agents (triptans) are best kept for moderate-severe headaches as have higher rate of adverse events than non-specific analgesics/metoclopramide

Prochlorperazine vs. Chlorpromazine

• Prochlorperazine (Stemetil)
  • 12.5mg IV with IV fluids 
  • Less hypotensive and sedating but also less effective

Migraine in pregnancy

• Most women improve in pregnancy
• No effect on pregnancy outcome
• First line: Paracetamol + Metoclopramide 10mg
• Second line: Aspirin 900mg (safest in second trimester)
  • Use limited to 48 hours in third trimester and weak evidence of harm in first trimester
• Third line: Opioids or sumatriptan (B3)
• Drugs to avoid
  • Chlorpromazine (Class D)
  • Ergotamine absolutely contraindicated

Trigeminal neuralgia

• Lightning or hot poker pain in trigeminal distribution lasting seconds but recurrently
• Can be triggered by light touching, eating, drinking, shaving or wind
• Common in middle to older age men
• Thought to be due to demyelination of sensory fibres in CNS portion of nerve root or brainstem most often due to compression by overlying vessel
• May be classic or secondary to another condition
• 15% of cases have a structural cause -> Consider MS and cerebellopontine angle tumors/acoustic neuromas
• Vascular compression may be amenable to microvascular decompression by neurosurgeons
• Treatment
  • Carbamazepine 200-400mg/day in divided doses increased by 200mg/day until relief up to 1200mg/day
  • If fails, lamotrigine or baclofen are alternatives
  • Refer to neurology
  • Consider MRA and neurosurgical referral if vascular compression thought to be causative

Occipital neuralgia

• Paroxysms of lancinating pain at back of head + hypersensitivity
• Mostly due to chronic neck tension or unclear
• Sometimes related to chronic degenerative cervical spine disease
• Occipital nerve block produces dramatic improvement and benefits can persist for weeks

Occipital nerve block

• Midpoint along nuchal ridge between occipital protuberance and mastoid process
• Greater occipital nerve runs medially to this and lesser occipital nerve runs laterally to this
• Angle slightly upwards, hit periosteum, aspirate, inject 1mL each side to get each nerve
• Bupivacaine 0.5% without adrenaline ideal

Idiopathic intracranial hypertension

• Most common in obese women
• 19.3/100 000 obese women between 20 and 44yo
• Headache (84%), transient visual obscurations (68%), back pain (53%) and pulsatile tinnitus (52%)
• 32% of patients report visual loss
• Untreated can lead to permanent visual impairment
• Tetracyclines are a leading cause
• Diagnostic criteria
  • Papilloedema (blurred disc margin)
  • No focal neurology
  • Elevated opening pressure >25cmH20 (>28 in children)
  • Normal CSF composition
  • Normal imaging

• A variant presents without papilloedema but has abducens nerve palsy (CN VI)
• In the absence of papilloedema or CN VI palsy, can make diagnosis if at least 3 neuroimaging findings present:
  • Empty sella
  • Flattening of posterior aspect of globe
  • Distension of perioptic subarachnoid space with or without tortuous optic nerve
  • Transverse sinus stenosis
• Knees should be extended for pressure measurement with manometer at level of right atrium
• Remove CSF until pressure 15-20cmH20 (1mL should lower CSF pressure by 1cmH20)

• Treatment
  • Oral acetazolamide lowers ICP and reduces symptoms
  • 250-500mg BD increased up to 4g/day
  • Dose escalation carries risk of paraesthesias, fatigue, decreased libido and metallic taste
  • Need ophthal follow-up of papilloedema and visual field testing
  • Long-term management can include CSF shunting, optic nerve fenestration for failing vision and weight loss

Intracranial hypotension

• Low-pressure headache seen post-LP, epidural or open dural procedures
• Non-cutting needle reduces the risk
• Can occur spontaneously, with Valsalva or following head or spine trauma
• May see CSF collection outside of epidural space (usually around the spinal cord), pituitary hypertrophy, sagged appearance of midbrain and brainstem
• Headache increases with upright posture and resolves in supination
• Associated symptoms include changes in hearing, vision, nausea, vomiting, diplopia
• LP has opening pressure <6cmH20
• Most patients symptoms spontaneously resolve but epidural blood patch can be performed

Carcinomatous meningitis

• 5-10% of cancer patients suffer leptomeningeal metastases
• Headache, CN deficits
• Risk factors include aggressive lymphoma and uncontrolled systemic disease
• MRI is diagnostic for meningeal enhancement (perform before LP as this can cause false-positive)
• LP may show raised opening pressure >20
• CSF flow cytometry (haematological) and cytology (solid tumors)

Cluster headache

• 0.4% of general population
• Mostly men, start in adulthood and occur in clusters with circadian or circannual rhythm typically
  • Daily for more than a week and remitting for at least 4 weeks
• Episodes typically unilateral, excruciating but self-limited
• 10% will suffer chronic form
• Typically pace around with ipsilateral autonomic features
• Treatment includes 100% O2 for 15 minutes and sumatriptan

Hypertensive headache

• Not associated with mild or moderate HTN
• Severe HTN >180mmHg/>120 may cause headache, especially if rapid and marked rise
• Consider aggressive treatment of both pain (fentanyl) and hypertension (IV hydralazine), especially if coexistent confusion/delirium/visual disturbance
• DDx
  • Aortic dissection
  • Hypertensive pulmonary oedema
  • MI
  • ICH
  • Cocaine
  • Pre-eclampsia
  • Phaeo/Conn’s
  • Urinary obstruction
  • RCVS (30% have HTN)
  • PRES

Coital headache

• Orgasmic headache
• Thunderclap but benign and no specific treatment required
• Diagnosis of exclusion as presents as SAH or reversible cerebral vasoconstriction syndrome
• Need imaging to rule out alternative diagnoses

Pituitary apoplexy

• Spontaneous haemorrhage or infarction of pre-existing pituitary adenoma
• Sudden, severe headache + ophthalmoplegia, reduced visual acuity, visual field defects, ALOC, meningismus, nausea, vomiting
• CT non-contrast and MRI show sellar mass and haemorrhage
• In first 1-2 hours, hyperacute haemorrhage may be best seen on non-contrast CT than MRI
• Pituitary adenomas and cerebral aneurysms have co-occurrence rate of 7%
• Rx – Immediate corticosteroids, neurosurgical consult + endocrine, ophthal, neuro, ICU consult

Third ventricular colloid cysts

• Rare cause of acute neurological deterioration and death
• Usually congenital, slow growing and benign
• Severe paroxysmal/episodic attacks of severe frontal headache with nausea and vomiting though to be due to intermittent obstruction of CSF flow

Sinusitis

• Purulent nasal discharge, nasal or facial congestion, hyposomia or anosmia with/without fever with headache, ear pain/fullness, halitosis or dental pain
• Treatment with antibiotics is beneficial

Tension headache

• Unclear cause but increased tension of head/neck muscles is a prominent feature
• FHx of headache often evident
• Associated with injury in childhood
• Most common precipitants are stress or poor sleep
• Ibuprofen 400mg > aspirin 600-1000mg > paracetamol >1g
  • All 50-70% successful

• International Headache Society
  • 30min to 7 days
  • At least 2 of:
    • Bilateral
    • Pressing and non-pulsatile
    • Mild to moderate severity
    • Not aggravated by usual activity
  • Need both of:
    • No nausea/vomiting
    • Only one of photophobia/phonophobia

Headache in pregnancy

• In women over 20 weeks with new headache
  • 1/3 have pre-eclampsia
  • Can essentially be excluded if not hypertensive but do need close follow-up (as HTN not always first presenting feature)
• Cause of headache in pre-eclampsia may be due to PRES, cerebral ischaemia from vasoconstriction, hypertensive encephalopathy or cerebral oedema
• Red flags
  • Headache + seizure/ALOC/papilloedema/visual disturbance/stiff neck/focal neurology
  • Sudden onset worse headache ever
  • New-onset migraine
  • Immunosuppressed
  • Change from usual pattern
  • Headache precipitated by exertion/valsalva
  • Unrelieved by analgesia
  • New headache that wakes her from sleep

• Imaging protocols remain relatively unchanged as compared to non-pregnant female
• If indicated, can perform MR or CT with contrast
  • Gadolinium may have adverse effects on fetus and should be avoided if possible
  • Iodinated contrast may have transient effects on fetal thyroid but no adverse clinical sequelae have been reported and should be used if indicated
  • CT head does not expose fetus to significant radiation

Last Updated on September 5, 2024 by Andrew Crofton