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[CUHK Medical Grand Rounds] Stroke mimics and thrombolytic therapy: Diagnostic challenges and clinical approach

Dr. Yannie Soo
Division of Neurology, Department of Medicine and Therapeutics, Prince of Wales Hospital, Hong Kong
Dr. Jill Abrigo
Division of Imaging and Interventional Radiology, Prince of Wales Hospital, Hong Kong
Prof. George Wong
Division of Neurosurgery, Department of Surgery, Prince of Wales Hospital, Hong Kong
13 Mar 2017

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Introduction

Ischaemic stroke is characterized by abrupt focal neurological dysfunction due to loss of blood supply to the brain resulting from thrombotic or embolic occlusion of supplying vessels. Clinical manifestation varies depending on vascular territories involved, with the most common presentation being sudden onset hemiparesis, slurred speech and facial asymmetry. However, a number of other conditions (eg, migraine, metabolic disorders, etc) can give rise to symptoms mimicking stroke. Differentiating ischaemic stroke from stroke mimics can be challenging in the hyperacute phase when thrombolytic therapy has to be considered in patients with nearly normal CT brain within a narrow therapeutic time window (ie, <4.5 hours from symptom onset, and a door-to-needle time <60 minutes).

In this article, we report a case of stroke mimic presenting as hyperacute stroke, which may have devastating outcome if thrombolytic therapy was given. 

Presentation and management

A 64-year-old lady with known diabetes mellitus and hypertension attended the hospital because of sudden onset of right upper limb and lower limb weakness. Prior to admission, she did sit-ups at home at 6:30 am.  After a few minutes of exercising, she experienced neck pain, which was soon followed by sudden onset of weakness affecting her right upper and lower limbs. She denied any neck sprain or trauma during her exercise. There was no headache, slurred speech, facial weakness or visual disturbance.

The patient attended the Accident and Emergency Department at 7:50 am. As she presented within the therapeutic time window with right hemiparesis, thrombolytic call was triggered and she was attended promptly by a neurologist and a stroke nurse. Upon physical examination, she was conscious and alert. First blood pressure documented was 234/114 mm Hg. She was in sinus rhythm and body temperature was normal. Neck stiffness was present. She had normal tone over the limbs. There was right hemiparesis. Medical Research Council grading of muscle power was grade 3 out of 5 over the right upper and lower limbs initially, which soon deteriorated to grade 0 with repeated examination 15 minutes later. Limb power was normal over the left side. Pinprick sensation and proprioception were normal. Reflexes and plantar response were normal. There were no cerebellar and cortical signs. Cranial nerves and speech were normal on serial examinations. H’stix was 7.0 mmol/L. Urgent brain CT was unremarkable, with no obvious early ischaemic change or acute haemorrhage. (Figure 1) 

StrokeMimicsCase_fig1

As her neck pain was precipitated by exercise, urgent CT angiography was performed to rule out dissection, which did not show any steno-occlusive disease. However, on further review of the CT angiogram source image, a hyperdense right intraspinal focus spanning from C2 to C7 levels was noted. It was extradural in location and 8–9 mm in thickness, causing significant spinal cord compression at C2 to C7. Contrast enhancement was also noted within the lesion at C3 to C4 levels, suggestive of active bleeding component. (Figure 2) The findings were highly indicative of acute epidural haematoma measuring 8 cm long with significant cervical cord compression. 

StrokeMimicsCase_fig2

The patient was referred to a neurosurgeon for emergency laminectomy, clot evacuation and decompression. Intraoperatively, a type 1 dural arterial venous fistula (AVF) was identified at C3/4 level. The spinal dural AVF was excised, and laminoplasty was performed. After surgery, the patient showed improvement in right limb power from grade 0 to grade 4. Postoperative MRI of cervical spine on day 2 showed no evidence of residual epidural haematoma. A focal T2-hyperintense intramedullary signal was noted at the right side of the cervical cord at C4/5 level, suspicious of cord oedema secondary to previous compression by epidural haematoma. (Figure 3) The patient continued to recover slowly with limb power and functional level normalized after 2 years.
StrokeMimicsCase_fig3

Discussion

Stroke mimics account for about 24 percent of cases admitted to stroke units and 4 percent of patients treated with intravenous thrombolysis.1,2 The most common diagnoses were headache, seizure, syncope and decompensation of previous medical or neurological conditions. Other less common conditions include vestibular disorder, psychiatric illness, mononeuropathy, metabolic disturbance (eg, severe hyperglycaemia or hypoglycaemia), sepsis, encephalopathy, neuromuscular disorder, other space-occupying brain lesions, etc.1,3 Differentiating mimics from ischaemic stroke may be difficult during the first few hours of symptom onset before the full-blown clinical picture is well manifested. Hence, many of these patients are managed as having ischaemic stroke initially until an alternative diagnosis can be confirmed at a later stage with repeated brain imaging and additional investigations. In the hyperacute phase, management is particularly challenging when decision for thrombolysis has to be made promptly during the time-critical triage. When stroke mimics are suspected and risk of thrombolysis is of concern, advanced imaging such as CT angiography or MR angiography, perfusion study or MRI brain may be needed.  Although the risk of symptomatic intracerebral haemorrhage with thrombolytic therapy is lower in stroke mimics than ischaemic stroke (0.5 percent in mimics vs 5.2 percent in stroke; risk ratio, 0.33; p=0.01), the outcome can be devastating or even fatal if thrombolysis is offered to patients with stroke mimics due to underlying bleeding pathology such as spinal dural AVF in this case.2

Spinal dural AVF is a rare disease, accounting for approximately 70 percent of spinal arteriovenous malformations. The lesions are thought to be acquired and affect predominantly middle-aged men. The symptoms are usually insidious in onset, with only 5 percent of patients having initial acute presentation. Clinical features can be nonspecific and diverse. The majority of patients develop progressive myelopathic symptoms, including lower limb weakness, gait disturbance and sensory symptoms, which may be worsened by activities that increase venous pressure (eg, exercise, valsalva maneuver, etc).4,5 In general, haemorrhage is uncommon due to the slow-flow nature. However, cervicomedullary dural AVFs have a much higher risk of haemorrhage as presenting symptoms.6 Surgical or endovascular treatment is needed for all patients. Fifty percent of untreated patients will be severely disabled within 3 years of lower limb weakness onset.

When differentiating stroke from mimics, localization of lesion by clinical features is of utmost importance. Although hemiparesis is a common stroke feature, it can be due to lesions in the spinal cord or other stroke mimics. Presence of localizing signs, such as dysphasia, hemi-neglect, cranial nerve or cerebellar involvement, can help localize the lesion to a single vascular territory and assist in diagnosis of stroke. The recently developed FABS clinical scoring system also helps stratify stroke mimics from cerebral ischaemia among patients with unremarkable brain CT. (Table)

StrokeMimicsCase_table

 In FABS, one score is given to each variable, with a total score of 6.  A score of
3 could identify patients with stroke mimcis with 90 percent sensitivity and 91 percent specificity.7 In this case, the patient’s FABS score was only 2. However, the absence of cranial nerve involvement despite dense hemiparesis and the presence of neck pain after exercise were red flags suggestive of cervical spine pathology. This highlights the importance of clinical localization and clinical-radiological correlation.

Distinguishing ischaemic stroke from stroke mimics can be challenging during the hyperacute phase when symptoms are dynamic and brain imaging is mostly normal. When stroke mimics are suspected, advanced imaging should be considered to guide treatment decision. Although adverse outcomes are uncommon with thrombolytic therapy in most patients with stroke mimics, it can lead to severe disabilities or even fatal events in those with underlying bleeding pathology. Clinical localization of lesion and cautious exclusion of acute haemorrhage is the key to safe thrombolysis in acute stroke.

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05 Nov 2019
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