Table 2

Differential diagnoses in hemiplegic migraine

Differential diagnosisMain featuresClue for differentialExaminations required
Cerebrovascular disease (ie, transient ischaemic attack (TIA) and ischaemic or haemorrhagic stroke)Sudden onset of neurological deficits
  • Sudden onset (TIA and stroke) vs gradual progressive spread (HM).

  • Prevalence of negative symptoms in TIAs and strokes.

  • Timing of the headache: after motor symptoms in HM and before them in haemorrhagic strokes.

CT, MRI, carotid ultrasound, transthoracic echocardiogram, special coagulation profiles, antiphospholipid antibody panel.
Cerebral amyloid angiopathy, even in absence of bleedingTransient episodes of focal neurological deficits known as amyloid spells
  • Recurrent and stereotyped episodes of paraesthesias, focal weakness or dysphasia, usually lasting several minutes.

  • Cortical superficial siderosis and microbleeds on brain MRI.

MRI including blood-sensitive sequences.
Epilepsy with hemiparesisLimb jerking, head-turning and loss of consciousness at seizure onsetProlonged migratory progression of aura over 30 min to hours vs short duration of seizures (sudden and usually <1 min).Electroencephalogram, MRI.
Brain tumoursProgressive neurological symptoms; neuroimaging and pathological examination are required
  • Precipitation of headache over Valsalva manoeuvre and bending over.

  • Headache is typical occipital or frontal.

CT, MRI, proton MR spectroscopy.
Stroke-like migraine attacks after radiation therapyHistory of radiation therapy
  • Typical neuroimaging features (thick cortical gyral enhancement).

  • History of remote irradiation (even after 20–30 years).

MRI with contrast.
Transient headache with neurological deficits and cerebrospinal fluid lymphocytosis (HaNDL)Spinal fluid lymphocytosis
  • Viral-like premonitory symptoms before one-third of HaNDL attacks.

  • Monophasic course, with resolution in 3 months.

  • Rare visual symptoms in HaNDL.

MRI, CSF examination.
Alternating hemiplegia of childhoodDystonia, epilepsy and cognitive impairment
  • Onset before 18 months.

  • Paroxysmal spells of hemiplegia, quadriplegia, choreoathetotic movements and nystagmus that disappear immediately after sleep.

  • Attacks may resume soon after awakening.

CT or MRI, electroencephalogram (preferably prolonged in order to capture an episode), ATP1A3 gene sequencing.
Central nervous system infectionsCerebrospinal fluid analysis and neuroimaging consistent with infection
  • Presence of systemic symptoms (in particular fever), nuchal rigidity and a variety of psychiatric and behavioural disturbances (ie, hallucinations and psychosis).

Complete blood count, erythrocyte sedimentation rate, CSF examination, MRI.
Hereditary and metabolic disorders (MELAS, CADASIL, hereditary haemorrhagic telangiectasias)Characteristic genetic mutations, lactate elevation, maternal or autosomal inheritance
  • Typical findings in MELAS: episodes of migrainous headache, stroke-like focal deficits, increased lactate in serum and CSF during the attack, MRI abnormalities, especially in the posterior cerebral cortex.

  • Cognitive impairment and sudden-onset focal neurological deficits are associated with CADASIL.

Lactate, CSF examination, electroencephalogram, CT and/or MRI, muscle biopsy, genetic testing.
  • CADASIL, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy; HM, hemiplegic migraine; MELAS, mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes syndrome.