Stroke And All Its Friends

By Malaika Jindal

CASE PRESENTATION

History

65-year-old female
Past medical history of type 2 diabetes mellitus, hyperlipidemia, hypertension, depression, malnutrition, alcohol use disorder and anemia
Presented to the emergency department (ED) for an urgent stroke evaluation due to 24 hours of worsening left-sided weakness and altered mental status (AMS).
She denied any dysarthria, dysphasia, acute visual changes, syncope, falls, palpitations, chest pain, shortness of breath, abdominal pain, nausea and vomiting, fevers or chills, or anticoagulant use.

Physical Exam

Vitals on arrival: BP 120/80, Pulse 91, temperature 36.4 °C, respiratory rate 22, SpO2 100%
NIHSS score on admission was 10, indicating a moderate stroke score
- Level of consciousness = 1
- Motor left arm = 2
- Motor left leg = 2
- Motor right leg = 2
- Limb ataxia = 2
- Sensation = 1
Constitutional: ill-appearing and toxic-appearing (Cachectic)
HEENT: normocephalic, no nuchal rigidity, normal sclera without injection, normal pinnae, no nasal deformity, no sinus drainage
Respiratory: breathing comfortably
Cardiology: normal heart sounds, regular pulse
Musculoskeletal: warm extremities without joint deformities
Skin: no rashes or jaundice

	R	L
Arm abduction	5	3
Elbow flexion	5	2
Elbow extension	5	1
Wrist extension	5	0
Finger exertion	5	0
Grip	5	1
Knee flexion	5	4
Knee extension	5	4
Ankle dorsiflexion	5	4
Ankle plantarflexion	5	5
Big toe extension	5	5
Cranial nerves	Normal
Reflexes and clonus	Normal

ED course + significant findings after admission

Urgent evaluation for stroke on arrival- no thrombolysis indicated, no large vessel occlusion on CT head
CT head findings: No ischemic core on noncontract CT or CT perfusion evaluation. Slightly diminished caliber of distal right MCA vessels, related to chronic right MCA infarct.
Found to be anaemic with haemoglobin 5.2 mg/dL – transfused in ED, 2 units of packed red blood cells
ECG, toxicology screen, urinalysis, prothrombin time and INR, troponin, ethanol, creatinine kinase, B12, folate, blood glucose – normal
Admitted to neurosciences ICU
EEG in ICU - no seizure activity but does show slight right slowing
MRI head in ICU 2 days after arrival - Multifocal late acute to early subacute ischemic right MCA territory infarcts, superimposed on large right MCA territory chronic infarct.

Figure 1: MRI head Figure 2: CT head Figure 3: normal ECG

What are the atypical stroke presentations? How can we minimize the chances of missing a stroke which presents with atypical features?

SUMMARY OF EVIDENCE

In the patient above, an initial CT scan exclude the possibility of acute stroke; however, an MRI scan done several days later confirmed a likely acute MCA infarct. This raises the clinical question - What are the atypical stroke presentations? How can we minimize the chances of missing a stroke which presents with atypical features?

A stroke chameleon is when a patient with a stroke displays atypical symptoms and is erroneously assigned an alternative diagnosis (i.e. a false negative) (1). Reassuringly, the rates of false negatives are lower than false positives (2–26% VS 30–43%) (2). However, majority of the research in this field involves retrospective studies, and hence the data reflect only those cases which were later found to have a stroke, which may underestimate false negative rates. Moreover, discerning a stroke chameleon has significant therapeutic and prognostic implications (3), due to delayed or missed acute management (thrombolysis and/or thrombectomy) and secondary preventative measures. The most common stroke chameleons are dizziness, headache, and AMS.

Dizziness is a subjective presenting complaint. One study found that patients’ description of their dizziness changed almost 50% of the time when they were asked similar questions repeatedly within 10 mins (4). However, dizziness is an important and relatively common (47–75 % patients) (1,2)sign of posterior circulation strokes and should raise concern for this in a patient with other stroke risk factors. Indeed, posterior-inferior cerebellar artery strokes can often present with isolated vertigo and vertebrobasilar TIAs can manifest as transient vertigo (5,6). In a meta-analysis reporting a false negative rate of 9%, isolated dizziness accounted for roughly 15 % of these (7). The main challenge lies in differentiating central and peripheral causes of dizziness. The TiTrATE tool has been suggested to overcome this. It focuses on timing, trigger, and targeted examination of dizziness to classify dizziness into triggered or spontaneous episodic and acute vestibular syndromes (8). The HINTs examination, including head impulse test, evaluation of nystagmus, and a test of skew, can then further help clinicians recognise central causes of dizziness in a patient with acute vestibular syndromes. Sensitivity and specificity of HINTs in diagnosing a central cause of vertigo have been reported to be as high as 95% and 97% respectively(2).

The relationship between headaches and stroke is complex. Other than the thunderclap headache for subarachnoid haemorrhage, the sensitivity and specificity of headaches for cerebrovascular accidents is low. Headache attributed to ischemic stroke (HAIS), which is common with vertebrobasilar strokes, can be recognised through a thorough headache and past medical history (5). A headache which develops in parallel with other symptoms/signs of stroke and evolves as these do is more likely to be HAIS. Additionally, a previous headache with altered characteristics or a new headache within 24 hours of other signs/symptoms is strongly suggestive of HAIS. Lastly, a history of cardioembolic events and large vessel occlusion make HAIS likely. Neurological examination in a patient with a headache should also include fundoscopy to establish papilledema as a sign of raised intracranial pressure associated with haemorrhagic strokes (3).

Bilateral thalamic infarcts and brainstem ischaemia can often cause AMS(5). One of the main challenges in a patient presenting with AMS is obtaining an accurate history. Without a collateral, toxic, metabolic or infectious causes may be considered instead, and signs like mild limb weakness and gaze palsy might be missed (3). However, the content and fluency of speech can help; delirium leads to normal fluency and tangential speech patterns. Contrastingly, aphasia due to a stroke tends to present with either sensible but non-fluent speech or non-sensical fluent speech. Additionally, clarifying symptom onset, duration, and fluctuation can also help with differentiation, as can presence of abnormal movements on examination.

Recommendations

Stroke chameleons present significant diagnostic challenges in ED due to their atypical presentation.
A detailed history and comprehensive and even extended neurological examination are key in identifying stroke chameleons.
Although CT and MRI imaging can often diagnose a stroke, as we saw in our patient these modalities cannot always be relied upon, particularly with prior strokes and early-on in symptom development.
CTs are not as sensitive as MRIs especially for detecting vertebrobasilar infarcts[7], however MRIs are expensive and more time-consuming to obtain.
Posterior circulation/vertebrobasilar strokes pose significant challenges while identifying stroke chameleons; neurology consultations should be considered early on when this is suspected.
Separating central causes of dizziness from peripheral pathology using the TiTrATE history and HINTs examination can be invaluable in preventing false negatives.
Although headaches are more common with haemorrhagic strokes, they can appear with ischaemic strokes too hence ED physicians should consider a cerebrovascular aetiology for atypical headaches.

References

Huff JS. Stroke mimics and chameleons. Emerg Med Clin North Am. 2002 Aug;20(3):583–95.
Liberman AL, Prabhakaran S. Stroke Chameleons and Stroke Mimics in the Emergency Department. Curr Neurol Neurosci Rep. 2017 Feb 22;17(2):15.
Moulin S, Leys D. Stroke mimics and chameleons. Curr Opin Neurol. 2019 Feb;32(1):54–9.
Newman-Toker DE, Cannon LM, Stofferahn ME, Rothman RE, Hsieh YH, Zee DS. Imprecision in patient reports of dizziness symptom quality: a cross-sectional study conducted in an acute care setting. Mayo Clin Proc. 2007 Nov;82(11):1329–40.
Candelaresi P, Di Monaco C, Pisano E. Stroke chameleons: Diagnostic challenges. Eur J Radiol Open. 2023 Dec;11:100533.
Wallace EJC, Liberman AL. Diagnostic Challenges in Outpatient Stroke: Stroke Chameleons and Atypical Stroke Syndromes. Neuropsychiatr Dis Treat. 2021;17:1469–80.
Tarnutzer AA, Lee SH, Robinson KA, Wang Z, Edlow JA, Newman-Toker DE. ED misdiagnosis of cerebrovascular events in the era of modern neuroimaging: A meta-analysis. Neurology. 2017 Apr 11;88(15):1468–77.
Newman-Toker DE, Edlow JA. TiTrATE. Neurol Clin. 2015 Aug;33(3):577–99.