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Year : 2020  |  Volume : 6  |  Issue : 2  |  Page : 126-129

A case of recurrent stroke with underlying adenocarcinoma: Pseudo-cryptogenic stroke

1 Department of Neurology, Himalayan Institute of Medical Sciences, Swami Ram Himalayan University, Dehradun, Uttarakhand, India
2 Department of Neurology, Max Institute of Neurosciences, Dehradun, Uttarakhand, India
3 Department of Radiology, Max Institute of Neurosciences, Dehradun, Uttarakhand, India
4 Department of Neuro-Critical Care, Max Institute of Neurosciences, Dehradun, Uttarakhand, India

Date of Submission04-Nov-2019
Date of Decision24-Feb-2020
Date of Acceptance17-Mar-2020
Date of Web Publication26-Jun-2020

Correspondence Address:
Dr. Deepak Goel
Department of Neurology, Himalayan Institute of Medical Sciences, Swami Ram Himalayan University, Doiwala, Dehradun - 248 016, Uttarakhand
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/bc.bc_49_19

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Stroke is the most common neurological disorders leading to early death. Early recognition of underlying mechanisms and etiology of stroke is important to prevent recurrence, mortality and disability. The term cryptogenic stroke or embolic stroke of undetermined sources is used where no etiology could be detected. We are describing this rare case of “recurrent stroke with undetermined etiology” finally proved to have an uncommon underlying etiology.

Keywords: Cryptogenic stroke, paraneoplastic stroke, recurrent stroke

How to cite this article:
Goel D, Sharma V, Pran MM, Gupta R, Keshri T, Shettigar U. A case of recurrent stroke with underlying adenocarcinoma: Pseudo-cryptogenic stroke. Brain Circ 2020;6:126-9

How to cite this URL:
Goel D, Sharma V, Pran MM, Gupta R, Keshri T, Shettigar U. A case of recurrent stroke with underlying adenocarcinoma: Pseudo-cryptogenic stroke. Brain Circ [serial online] 2020 [cited 2023 Jun 6];6:126-9. Available from: http://www.braincirculation.org/text.asp?2020/6/2/126/287742

  Introduction Top

Stroke is leading cause of death and disability among all medical condition. Cryptogenic stroke (undermined etiology) is challenging condition for the stroke physicians and prevention of recurrence is often based on antiplatelates. Through our case report we are presenting the same challenge and recommend that searching for the underlying cause in stroke patients is important for prognosis.

  Case Report Top

This 62-year nonsmoker female admitted with us in October 2017 with sudden onset right hemianopia caused by left parieto-occipital infarction in posterior cerebral artery (PCA) territory [Figure 1]. She was not having any old medical history of any systemic disease like diabetes, hypertension or coronary artery disease. She was investigated and found to have normal echocardiography, normal brain and neck angiography by computerized tomography (CT) and 24 h holter monitoring. Her glycoselated hemoglobin, lipid profile and thyroid profile was normal. Her erythrocyte sedimentation rate (ESR) was 56 mm/h and X-ray chest posteroanterior (PA) view was normal. Then she was put on antiplatelates and rosuvastatin and discharged with diagnosis of cryptogenic PCA stroke. About 2 months later this female had sudden speech arrest and found to have left middle cerebral artery infarction in superior division [Figure 2]. This time we put on double antiplatelates and checked for thrombophilia profile that also came negative. Within 1 week of dual antiplatelates therapy patient had developed third stroke in right PCA territory and became blind now she was put on enoxaparin 0.6 mg subcutaneous twice a day. Another new infarction occurred in right middle cerebral artery infarction on all treatment [Figure 3] and [Figure 4]. Now our focus was to do trans-esophageal echo for persistent foramen ovale and aorta screening for any plaque. Trans-esophageal echo done outside was normal. CT Aortography was done which was also normal but accidently we found splenic and right renal infarction [Figure 5]. Additional finding was suspected and lung nodules were seen in the basal areas bilaterally [Figure 6]. X-ray chest PA view was repeated which was again normal. We sent vasculitis and para neoplastic profile of the patient and planned for biopsy. Her vasculitis profile was negative and her CEA and CA 125 were highly positive. Her biopsy from chest nodule showed anaplastic adenocarcinoma. Finally the patient proved to have recurrent stroke with underlying anaplastic adenocarcinoma. Even after extensive investigations exact mechanism of stroke could not be established, although we have ruled out prothrombotic state (negative) but we have not estimated D-dimer level.
Figure 1: Diffusion weighted imaging – Magnetic resonance imaging showing left posterior circulation stroke

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Figure 2: Diffusion weighted imaging – Magnetic resonance imaging showing left middle cerebral artery stroke

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Figure 3: Diffusion weighted imaging – Magnetic resonance imaging showing right posterior circulation stroke

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Figure 4: Diffusion weighted imaging - Magnetic resonance imaging showing right middle cerebral artery stroke

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Figure 5: Computerized tomography abdomen showing spleen infarction

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Figure 6: Computerized tomography chest showing lung nodule

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  Discussion Top

In Indian literature 20%–27% patients suffers from stroke due to undetermined etiology classified as cryptogenic stroke (CS).[1],[2] The rate of CS has been quoted rather more frequently (26%–40%) in patients of recurrent embolic stroke.[3],[4],[5],[6] The current stroke guidelines recommended antiplatelates for secondary stroke prophylaxis in patients with undetermined etiology. But there is no specific guidance for those patients who have recurrent stroke (cryptogenic) on antiplatelates. One nonsystemic review suggests long duration holter recording (72 h) to rule out paroxysmal atrial fibrillation.[7] Our case was difficult to manage for us as she had recurrent episodes in-spite of all treatment and we could not find the etiology initially so labeled as CS. In TOAST classification system, stroke with undetermined etiology also includes patients of stroke with incomplete work-up.[8] In year 2014, the term embolic stroke of undetermined sources (ESUS) was coined by CS/ESUS international working group.[9] ESUS term can be used with nonlacunar stroke in absence of; (1) intracranial/extracranial atherosclerosis causing more than 50% luminal stenosis supplying to symptomatic zone; (2) major cardio-embolic sources including permanent/paroxysmal atrial fibrillation; and (3) no other specific cause of stroke. The specific investigations for long list of uncommon causes of stroke are very costly and not available everywhere especially in countries like India therefore, CS/ESUS is commonly used after common causes have been ruled out in clinical practice. In our cases infarctions were bilateral and were in both anterior as well as posterior circulation territories. This multifocal distribution is only possible when embolization occurs from either heart or arch of aorta. We planned for trans-thoracic echocardiography and CT aortography. It was accidental detection of pleural nodules during arotography which led to accurate diagnosis of the case.

Stroke in cancer can be divided into three categories; (1) those who have typical vascular risk factors for stroke with cancer; (2) those who have no other risk factor but only malignancy that diagnosed prior to the stroke and (3) those who diagnosed as CS initially and later found to have underlying malignancy. Therefore, many cases with unknown malignancy presenting with stroke can be classified as CS/ESUS. Till date several studies have tried to correlate the specific cancer type having strong association with stroke. In one study, among 1,274 patients of stroke 12% had additional diagnosis of cancer, with uro-genital, gastrointestinal and breast being the most common.[10] In other studies patients with lung, pancreas, colorectal, breast, and prostate had higher incidence of stroke.[11]

Multiple mechanisms may be linked in stroke with cancer like hypercoagulability, paradoxical emboli, nonbacteriral thrombotic endocarditis (NBTE), and direct tumor effects. In one study 8 of 24 patients with cancer were found to have NBTE which was frequently associated with adenocarcinoma.[12] It is common to presume a diagnosis of hyper-coagulability in patient with recurrent stroke of undetermined etiology till they found underlying cancer as etiology.[12],[13] In NBTE, sterile vegetations develop on aortic and/or mitral valve. Transesophageal echocardiography (TEE) is thought to be more sensitive for diagnosis.[14] We could not found any evidence of NBTE on TEE done in our patient. Systemic emboli occur in nearly 50% of patients with NBTE with cerebral emboli being quite common.[14],[15] The diffusion magnetic resonance imaging pattern in patients with NBTE was uniformly found to have multiple widely distributed small and large strokes while those with bacterial endocarditis had more varied stroke patterns.[16]

As such it is unclear that which subset of patients should be considered for screening of cancer in CS. Existing reports indicates that elderly patients with (1) recurrent embolic stroke without stroke related risk factors, (2) patients with cerebral and systemic emboli, (3) patients with stroke in presence of “B” symptoms such as unexplained fever, weight loss and malaise, (4) high serum markers known to correlate with the diagnosis of cancer (such as D-Dimer, Ferritin and ESR of >100).

Our patient had continued to have new strokes while getting antiplatelates and low molecular heparin. In patients with cancer and stroke, having classical risk factors for stroke like hypertension, diabetes, atrial fibrillation, or carotid artery disease follow same protocols for disease modification as in without cancer. It remains to be seen whether there is a role for antiplatelates or anticoagulants in the secondary prevention of cancer related stroke. Based on limited data available it can be assumed that anticoagulation is superior for the prevention of hyper-coagulability induced stroke in cancer patients if associated with high D-dimer level. D-dimer level was not estimated in our case so again we can't associate the results of failed anticoagulation in our case.

The case presented here convey the important message that any elderly patient presenting with new onset or recurrent stroke without known risk factors of stroke underlying malignancy should be ruled out before labeling the case as cryptogenic.

  Conclusions Top

Our case present the diagnostic and therapeutic challenges related so called “cryptogenic stroke” with underlying occult malignancy. Systemic and cerebral embolic stroke in short duration without classical risk factors of stroke needs detail evaluation for underlying malignancy.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Kaul S, Sunitha P, Suverna A, Meena AK, Uma M, Reddy JM. Subtypes of ischemic stroke in a metropolitan city of South India (One year data from hospital based stroke registry). Neurol India 2002;50:S8-14.  Back to cited text no. 1
Dalal PM. Burden of stroke: Indian perspective. Int J Stroke 2006;1:164-6.  Back to cited text no. 2
Grau AJ, Weimar C, Buggle F, Heinrich A, Goertler M, Neumaier S, et al. Risk factors, outcome, and treatment in subtypes of ischemic stroke: The German stroke data bank. Stroke 2001;32:2559-66.  Back to cited text no. 3
Kolominsky-Rabas PL, Weber M, Gefeller O, Neundoerfer B, Heuschmann PU. Epidemiology of ischemic stroke subtypes according to TOAST criteria: Incidence, recurrence, and long-term survival in ischemic stroke subtypes: A population-based study. Stroke 2001;32:2735-40.  Back to cited text no. 4
Petty GW, Brown RD Jr., Whisnant JP, Sicks JD, O'Fallon WM, Wiebers DO. Ischemic stroke subtypes: A population-based study of incidence and risk factors. Stroke 1999;30:2513-6.  Back to cited text no. 5
Sacco RL, Ellenberg JH, Mohr JP, Tatemichi TK, Hier DB, Price TR, et al. Infarcts of undetermined cause: The NINCDS Stroke Data Bank. Ann Neurol 1989;25:382-90.  Back to cited text no. 6
Hariri E, Hachem A, Sarkis G, Samer N. Optimal duration of monitoring for atrial fibrilation in cryptogenic stroke: A non-systemic review. Biomed Res Int 2016;2016:1-0.  Back to cited text no. 7
Adams HP Jr., Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, et al. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in acute stroke treatment. Stroke 1993;24:35-41.  Back to cited text no. 8
Hart RG, Diener HC, Coutts SB, Easton JD, Granger CB, O'Donnell MJ, et al. Embolic strokes of undetermined source: The case for a new clinical construct. Lancet Neurol 2014;13:429-38.  Back to cited text no. 9
Stefan O, Vera N, Otto B, Heinz L, Wolfgang G. Stroke in cancer patients: A risk factor analysis. J Neurooncol 2009;94:221-6.  Back to cited text no. 10
Navi BB, Reiner AS, Kamel H, Iadecola C, Elkind MS, Panageas KS, et al. Association between incident cancer and subsequent stroke. Ann Neurol 2015;77:291-300.  Back to cited text no. 11
Taccone FS, Jeangette SM, Blecic SA. First-ever stroke as initial presentation of systemic cancer. J Stroke Cerebrovasc Dis 2008;17:169-74.  Back to cited text no. 12
Uemura J, Kimura K, Sibazaki K, Inoue T, Iguchi Y, Yamashita S. Acute stroke patients have occult malignancy more often than expected. Eur Neurol 2010;64:140-4.  Back to cited text no. 13
Dutta T, Karas MG, Segal AZ, Kizer JR. Yield of transesophageal echocardiography for nonbacterial thrombotic endocarditis and other cardiac sources of embolism in cancer patients with cerebral ischemia. Am J Cardiol 2006;97:894-8.  Back to cited text no. 14
El-Shami K, Griffiths E, Streiff M. Nonbacterial thrombotic endocarditis in cancer patients: Pathogenesis, diagnosis, and treatment. Oncologist 2007;12:518-23.  Back to cited text no. 15
Singhal AB, Topcuoglu MA, Buonanno FS. Acute ischemic stroke patterns in infective and nonbacterial thrombotic endocarditis: A diffusion-weighted magnetic resonance imaging study. Stroke 2002;33:1267-73.  Back to cited text no. 16


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]

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