ISCHEMIC STROKE

Stroke mimics

Created 24/05/2023, last revision 02/06/2023

• stroke is a medical emergency presenting with focal neurological deficits; stroke mimics are non-vascular conditions that present with symptoms similar to those of stroke.
• incidence of stroke mimics is ~3-10% [Okano, 2018]   [Winkler, 2009]   [Scott, 2003]   [Tsivgoulis, 2011]
  • most common are epileptic seizures, migraine, brain tumors, functional disorders, TGA, hypoglycemia and other metabolic disorders, syncope, or intoxication
• the existence of mimics causes troubles in the acute setting (should we initiate thrombolysis?) but also in the chronic stage (was it a recurrent stroke? Should we change secondary prevention? Is CEA indicated for carotid stenosis?)
  • incorrectly administered IVT may harm the patient, although available data show the relative safety of thrombolysis in stroke mimics [Tsivgoulis, 2011]
  • on the other hand, failure to provide adequate treatment to unrecognized stroke patients reduces their chances of recovery
• it is essential to consider stroke mimics in the differential diagnosis of every patient with suspected stroke; however, potential candidates for thrombolytic therapy should not be excluded based on the sole concern that their neurological symptoms may be due to stroke mimics
• several features (red flags) may help differentiate the stroke mimics from an actual stroke (see table)

• a rare cause of transient symptoms
• more commonly occurring in older patients (> 60 years) [Beitzke, 2011]
• MRI confirms the diagnosis (with almost 100% sensitivity); thin-sliced multiplanar CT is also a valuable emergency diagnostic tool (however, MRI remains crucial and mandatorily and has to be completed within the next 24–72 hours)  [Ertl, 2014]

→ more here

• stroke mimic that is associated with ↑risk of ICH after IVT administration

→ cerebral amyloid angiopathy (CAA)

• an epileptic seizure may mimic a stroke, and the patient may be mistakenly treated with thrombolysis after the seizure
  • the real problem is posed by conditions such as Todd’s hemiparesis, complex partial seizures mimicking symbolic dysfunction, etc.
    
  • epileptic seizures can also occur in the terrain of previous ischemia (poststroke epilepsy) and transiently worsen the previous deficit
• however, epileptic seizures can also occur during an acute stroke (~1-6%), and the patient may not receive appropriate recanalization therapy if misdiagnosed as an isolated seizure  [Sylaja, 2006]  [Killpatrick, 1990]
  • an epileptic seizure at the onset of stroke is not a contraindication to thrombolytic therapy, provided that imaging demonstrates stroke (occlusion on CTA, perfusion mismatch, etc.)
    

• a frequent stroke mimic
• migraine aura without the headache and the first attack of basilar or hemiplegic migraine represent the main problem
• symptoms usually develop more slowly, spread or migrate, and are typically followed by headache with nausea/vomiting and photo/phonophobia (see table)
• migraine is likely:
  • in younger patients with a history of similar recurrent attacks and absence of vascular risk factors
  • with positive symptoms developing within minutes or tens of minutes (gradual onset)
    • flashes, bright lines, and scintillations that begin in part or half of the visual field and may extend to the entire visual field or often move across the visual field
    • paresthesias, usually spreading or moving over half the body (march), including the head, over minutes to tens of minutes
  • with subsequent development of headaches
• history of repeated uniform attacks with a slow onset may be helpful
• if symptoms resolve quickly, DDx of TIA can be problematic (mainly if the condition occurs for the first time)
• imaging, including MR-DWI or CT perfusion, is normal
• dissection should be ruled out in new-onset hemicrania with focal findings!

• stroke-like migraine attacks after radiation therapy (SMART) syndrome is a delayed complication of brain radiotherapy (usually associated with doses of 50 Gy or more)
• onset of symptoms varies widely from 1 to 40 years after initial radiation therapy
• symptoms last from several hours to several weeks and typically consist of:
  • recurrent headaches with migraine-like aura
  • seizures
  • stroke-like symptoms referable to a unilateral cortical region (motor deficits, paresthesia, aphasia, and visual disturbances)
• full recovery in most patients was reported
• imaging findings may include unilateral increased T2 signal with associated gyral thickening and transient cortical enhancement in the temporal, parietal, and occipital lobes; the process spares the white matter
• the pathogenesis is not as well understood as with other complications of radiation, such as leukoencephalopathy and radiation necrosis
  • proposed endothelial dysfunction may lead to disruption of the blood-brain barrier with subsequent marked cortical enhancement
  • some case reports have reported nonspecific gliosis without inflammation or no identifiable histopathologic abnormality

• mental status changes and epileptic seizures with possible Todd’s hemiparesis predominate in the majority of encephalopathies (renal, hepatic failure)
  • impaired level of consciousness may progress
  • complications may occur even after hemodialysis (see below)
• neuroglycopenia and Wernicke’s encephalopathy, in particular, may present with focal symptoms, posing the greatest difficulty in distinguishing a true stroke

• may accompany decompensated hypertension (usually with SBP > 220 mmHg/DBP  > 120 mmHg)   → hypertensive crisis
  • the rate of BP increase seems to be more important than its absolute value
• failure of autoregulation leads to cerebral edema
• clinical presentation:
  • confusion, headache, nausea/vomiting, visual disturbances, focal symptoms
  • papilledema and hypertonic retinopathy on ophthalmoscopy
  • reversible posterior hypertensive encephalopathy (PRES) may occur

• DDx of a first attack of multiple sclerosis (MS) from a stroke and recognition of the coincidence of MS and acute stroke may pose problems
  • the most difficult decision is whether administer TL or not
    
  • age and the presence or absence of risk factors cannot be relied upon (stroke is increasingly seen in young patients without vascular risk factors)
  • in addition, MS can manifest at older ages (40-50 years) when patients may already have multiple vascular risk factors present
• findings of occlusion on CTA, perfusion disturbances on CTP, or early signs of ischemia (ASPECTS<10) are helpful
• MR DWI
  • even in acute plaque, there may be diffusion restriction on DWI ⇒ small lesions cannot be reliably distinguished radiologically from lacunar infarct  
  • the demonstration of postcontrast lesion enhancement may help
  • in larger ischemic lesions can be distinguished by the typical shape and localization corresponding to some arterial territory

• typical association with change of position → see here
• provocation of dizziness and nystagmus during positional tests (Dix-Hallpike, Seemont, Log-roll, etc.)

• a sudden, temporary (< 24h) episode of memory loss with the absence of other neurological signs that can’t be attributed to a more common neurological condition, such as epilepsy or stroke  → more here

• tetany is usually manifested by involuntary muscle cramps or spasms due to abnormal alterations in the body’s electrolytes (especially calcium)
• difficulties can cause isolated paresthesia associated with tetany → see here

• these disorders can be differentiated by neuroimaging (CT/MRI)
• intracerebral or spinal hemorrhage
  • differentiate hemorrhagic infarction (arterial and venous) 
• tumor – acute deterioration may be caused by bleeding into the tumor due to decompensation of edema or epileptic seizure
• neuroinfectious diseases    
  • fever, cephalea, the elevation of inflammatory markers, alteration of mental status, epileptic seizures
• autoimmune encephalopathy
  • gradual onset
  • typical MRI presentation with a predilection to temporal lobes
  • EEG finding
  • autoantibodies (not available in the acute stage)
• PRES

• first attack and conversion disorders with a focal deficit (paresis, etc.) pose the biggest problem; the situation is easier with anxiety disorders
• a simplified classification can be made:
  • panic attacks, anxiety
  • conversion somatomorphic disorders
  • simulation
• in the first attack, an organic cause must always be carefully ruled out (negative imaging, incl. DWI)
• how to proceed during clinical examination:
  • assess the signs while distracting the patient’s attention (fluctuations in the severity of paresis)
  • objectify the findings using EMG, EP, brain imaging
  • look for discrepancies and fluctuations in motor impairment (e.g., rapid fall in Minagazzini in a walking patient, seeing a paretic patient walking in a hospital park, etc.)
  • investigate the exact borders in hemihypesthesia (in psychosomatic disorders the border is usually in the middle)
  • search for the provoking moment and potential benefit of the current condition (partner’s interest, financial motivation, etc.)
  • note emotional inertia to severe deficits (e.g., a smiling patient who has suddenly “gone blind”)
    • exclude rare Anton (denies blindness) and inverse Anton syndrome (sees but thinks he is blind)!
  • look for psychiatric history
• clinical presentation
  • in somatomorphic disorder or simulation, it is not uncommon to have impaired mobility of one or more limbs, impaired hearing or blindness, and bizarre gait
  • there is a long history of difficulties, repeated hospitalizations in various departments with negative findings
  • a vivid depiction of polymorphic difficulties, extensive documentation, keeping a diary of difficulties, etc.
  • absence of pyramidal phenomena, trophic changes in paresis, etc.