CME INDIA Presentation by Dr. Manan Mehta, MD, DM Neurology, Mehta Neurology Center, Vadodara.
Stroke stands as the fifth leading cause of death. In US it presents as two primary subtypes: hemorrhagic, constituting 17%, and ischemic, making up 83% of cases. Cryptogenic strokes, accounting for 15-40% of all strokes, add complexity to the landscape.
Notably, women face a higher lifetime risk of stroke compared to men. Additionally, racial disparities emerge, with Blacks and Hispanics experiencing a greater incidence of ischemic strokes than Caucasians. Historically, cryptogenic stroke incidence skewed towards older patients, but recent findings from the Northern Manhattan Stroke Study (NOMASS) challenge this trend, suggesting a higher incidence. Here we present few eye-opening cases of cryptogenic stroke.
First see this case
- 65/F
- HTN – Well controlled
- No cardiac Illness
- Normal Lipids
- Acute onset altered sensorium – with quadriparesis (right > left)
- RBS – 200
- ECG – Sinus rhythm, Normal
What happened later?
- Holter – WNL
- Negative ANA
- Transesophageal ECHO – normal
- DSA – normal Angio and Veno
Diagnosis
- Embolic Stroke of Undetermined Source
- Treatment with Antiplatelet and statin
- Patient is doing very well
Need to know 3 terms
- Etiology
- Risk factors
- Mechanism
Toast Classification
Classifying Ischemic Stroke, from TOAST to CISS. Courtesy: Chen PH, Gao S, Wang YJ, Xu AD, Li YS, Wang D. Classifying Ischemic Stroke, from TOAST to CISS. CNS Neurosci Ther. 2012 Jun;18(6):452-6
(A) Large Vessel Occlusion
- ICA, MCA(M1) or Vertebro-Basilar
- More deficits
- Poor outcome
- Smoking, DM, Hyperhomocystenemia
- Thrombolysis and Mechanical Thrombectomy
Brain MRI findings. (A) MR angiography demonstrates loss of flow distal to the right middle cerebral artery bifurcation. (B) Axial diffusion-weighted image showing hyperintensity in the territory of right middle cerebral artery
(B) Cardio Embolic
- Atrial Fibrillation
- Valvular Heart Disease
- Severe LV dysfunction
- LAA thrombus/ LV clot
- Infective endocarditis
- Anticoagulation is the treatment of choice
(C) Small Vessel Arteriosclerosis
- Lacunar strokes – Basal ganglia, Internal Capsule and Pons
- Hypertension
- Dyslipidemia
- DM
- Double Antiplatelets and Statins
- Risk Factor Modifications
Lacunar infarct MRI
D) Stroke of Other determined Etiology
- Vasculitis
- Dissection
- Drug Abuse
- Arteritis
- Vasospasm
(E) Brain infarction – not attributable to
- Any source of definite cardio-embolism
- Large artery atherosclerosis
- Small artery disease
- Despite a standard vascular, cardiac, and serologic evaluation
- Embolic stroke of undetermined source — (ESUS) represents a subset of cryptogenic stroke
- 20-30%
Possible Mechanisms for Cryptogenic Stroke
| Paroxysmal AF |
| Aortic Arch Atheromas |
| Hypercoagulable States (Occult malignancy, Post Pregnancy, Genetic) |
| Paradoxical Embolism (PFO, ASD) |
| Sub stenotic (<50%) Atherosclerotic vessels |
| Others |
Paroxysmal AF
| Usually missed on ECG and short-term cardiac monitor |
| Requires at least 72 hours of Holter |
| Loop Recorder devices – 7-30 days (ambulatory) |
| Anticoagulation is a reasonable choice once AF detected |
| Usually missed on ECG and short-term cardiac monitor |
| Requires at least 72 hours of Holter |
| Loop Recorder devices – 7-30 days (ambulatory) |
| Anticoagulation is a reasonable choice once AF detected |
Arch of Aorta – Plaques
- Common source of Embolus
- Complex plaque – Ulcerated or > 4mm
Courtsey:https://www.stroke-manual.com/aortic-arch-atherosclerosis/
Paradoxical Embolism
- PFO, ASD
- Determined mainly on TEE and Bubble study
- RoPE score
Courtsey: https://www.stroke-manual.com/patent-foramen-ovale-pfo/
- The RoPE score evaluates the likelihood that a detected PFO in the context of an otherwise cryptogenic stroke is causally linked to the stroke rather than being an incidental discovery. The RoPE score has a scale of 0 to 10, where scores of 0 to 3 suggest a minimal likelihood of the stroke being attributed to the PFO, and a score of 10 indicates an approximately 90% probability of the stroke being linked to the PFO.
- PASCAL integrates the RoPE score with the presence or absence of high-risk PFO features to assess the probability of the PFO being causally associated with the index stroke.
Courtesy: The RoPE Score and PASCAL Classifications. Available from: https://www.ncbi.nlm.nih.gov/books/NBK592989/table/tbl001
ASA, atrial septal aneurysm; LS, large shunt; PASCAL, PFO-Associated Stroke Causal Likelihood; PFO, patent foramen ovale; RoPE, Risk of Paradoxical Embolism.
SCOPE Study (2023): It showed that among patients aged 18 to 60 years with PFO-associated stroke, risk reduction for recurrent stroke with device closure varied across groups classified by their probabilities that the stroke was causally related to the PFO.
Sub-Stenotic Atherosclerosis
- < 50% stenosis
- But – Unstable plaque, Intraplaque hemorrhage, > 3mm, Rupture of Plaque
- Vessel Wall Imaging
VW-MR imaging to differentiate among causes of intracranial arterial stenosis when angiography findings are inconclusive. This patient had multiple recent infarcts in the pons. MR angiogram
Courtsey: American Journal of Neuroradiology February 2017, 38 (2) 218-229; DOI: https://doi.org/10.3174/ajnr.A4893
Others
- Occult Malignancy
- Elderly, Raised D-Dimer, constitution symptoms
- Hypercoagulable state
- APLA, hyperhomocytenemia, other genetic
- RVCS
- Eclampsia, Vasospasm, Drugs (tacrolimus, vincristine, cocaine)
- Dissection
- Neck Manipulation, Trauma
- Vasculitis
- Lupus, Takayasus, Primary CNS vasculitis
See this case
- Orthopedic Resident
- Sudden jerk during Fracture reduction
- Heard an abnormal sound in the neck
- Acute Ataxia with vomiting
- Smoked very occasionally
- No family history of stroke
- All traditional work up was negative
Right Cerebellar Infarct – Right VA Dissection
Case
- Post Renal Transplant
- Day 18
- Sudden Confusion and vision loss
- On Tacrolimus
- S. Tac level – 22 ng/ml
- Post Renal Transplant
- Day 18
- Sudden Confusion and vision loss
- On Tacrolimus
- S. Tac level – 22 ng/ml
RCVS – Reversible Vasoconstriction Syndrome
Case
- 18-year-old Boy
- DOI – 7 Months
- Failed in 12th
- Depression – suicidal attempts
- Headache
- Change of Personality
Acute right Hemiparesis – 3 days
Primary CNS Vasculitis
- Raised ESR, CRP
- Normal Routine profile
- Normal ECHO
- Normal TEE
- Negative ANA
- DSA – Classical Stenosis and Ballooning (Beaded Appearance)
Work up in Cryptogenic Stroke
| Traditional Work up: DM, HTN, Lipids, ECG, Echo, Doppler |
| High suspicion of embolism |
| Holter or Long-term Ambulatory Recorders |
| Transesophageal ECHO with Bubble study |
| Atheromatous Plaques |
| Arch of Aorta |
| Vessel Wall Imaging (unstable Plaques) |
| Other depending on the history |
| ANA, APLA, Homocysteine, Sickle cell, Look for dissection, Drugs |
Treatment for Cryptogenic Stroke
- Acute Therapy remains same – IV TPA/TNK and Mechanical Thrombectomy
- For long term
- Depends on the etiology that we establish
- Also – BASICS remain the same
- Smoking, Tobacco, Sugar, BP and Lipids
- ESUS/Cryptogenic – Single stroke – Antiplatelet > Anticoagulation
- ESUS/Cryptogenic – Recurrent – Anticoagulation (DOAC)
- Presence of AF – Anticoagulation (DOAC)
- PFO – Closure
- Compared with other stroke subtypes, cryptogenic stroke tends to have a better prognosis and lower long-term risk of recurrence.
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References:
- Chen PH, Gao S, Wang YJ, Xu AD, Li YS, Wang D. Classifying Ischemic Stroke, from TOAST to CISS. CNS Neurosci Ther. 2012 Jun;18(6):452-6. doi: 10.1111/j.1755-5949.2011.00292.x. Epub 2012 Jan 24. PMID: 22268862; PMCID: PMC6493455.
- Kent DM, Saver JL, Kasner SE, et al. Evaluating Therapies to Prevent Future Stroke in Patients with Patent Foramen Ovale-Related Strokes — The SCOPE Study [Internet]. Washington (DC): Patient-Centered Outcomes Research Institute (PCORI); 2023 Apr. Table 1, The RoPE Score and PASCAL Classifications. Available from: https://www.ncbi.nlm.nih.gov/books/NBK592989/table/tbl001/ doi: 10.25302/04.2023.RS.SCOPE2019001
- Kent DM, Saver JL, Kasner SE, et al. Evaluating Therapies to Prevent Future Stroke in Patients with Patent Foramen Ovale-Related Strokes — The SCOPE Study [Internet]. Washington (DC): Patient-Centered Outcomes Research Institute (PCORI); 2023 Apr. Available from: https://www.ncbi.nlm.nih.gov/books/NBK592989/ doi: 10.25302/04.2023.RS.SCOPE2019001
- Benjamin EJ, Muntner P, Alonso A, et al. Heart disease and stroke statistics-2019 update: a report from the American Heart Association. Circulation 2019;139:e56-e528.
- White H, Boden-Albala B, Wang C, et al. Ischemic stroke subtype incidence among whites, blacks, and hispanics: the Northern Manhattan Study. Circulation 2005;111:1327-31.
- Williams LS, Garg BP, Cohen M, Fleck JD, Biller J. Subtypes of ischemic stroke in children and young adults. Neurology 1997;49:1541.
- American Journal of Neuroradiology February 2017, 38 (2) 218-229; DOI: https://doi.org/10.3174/ajnr.A4893
- Acampa, M., Lazzerini, P.E., Lattanzi, S. et al. Cryptogenic stroke as a working diagnosis: the need for an early and comprehensive diagnostic work-up. BMC Neurol 23, 153 (2023). https://doi.org/10.1186/s12883-023-03206-6
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