Accepted Manuscript Acute Supratentorial Ischemic Stroke with Ipsilateral Hemiparesis: Pathomechanism and Management Challenges Devi Prasad Patra, MD, M.Ch, Vinayak Narayan, MD, M.Ch, Amey Savardekar, MD, M.Ch, Rimal Hanif Dossani, MD, Christian Cajavilca, MD, Vijaykumar Javalkar, MD, Eduardo Gonzalez-Toledo, MD, Hugo H. Cuellar, MD, PhD PII: S1878-8750(18)31650-4 DOI: 10.1016/j.wneu.2018.07.172 Reference: WNEU 8737 To appear in: World Neurosurgery Received Date: 24 January 2018 Revised Date: 18 July 2018 Accepted Date: 20 July 2018 Please cite this article as: Patra DP, Narayan V, Savardekar A, Dossani RH, Cajavilca C, Javalkar V, Gonzalez-Toledo E, Cuellar HH, Acute Supratentorial Ischemic Stroke with Ipsilateral Hemiparesis: Pathomechanism and Management Challenges, World Neurosurgery (2018), doi: 10.1016/ j.wneu.2018.07.172. This is a PDF file of an unedited manuscript that has been accepted for publication. 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ACCEPTED MANUSCRIPT P age |1 Case report Acute Supratentorial Ischemic Stroke with Ipsilateral Hemiparesis: Pathomechanism and Management Challenges Authors RI PT Devi Prasad Patra1, MD, M.Ch; Vinayak Narayan1 MD, M.Ch; Amey Savardekar1, MD, M.Ch; Rimal Hanif Dossani1, MD; Christian Cajavilca2, MD; Vijaykumar Javalkar2, MD; Eduardo Gonzalez-Toledo3, MD; Hugo H Cuellar1,3, MD, PhD Department of Neurosurgery1, Neurology2, Radiology3 SC Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA Dr. Hugo Cuellar Associate Professor Department of Neurosurgery M AN U Corresponding Author Louisiana State Health Sciences Center – Shreveport 1501 Kings Highway TE D Shreveport, LA 71130-3932 Phone: (318) 655-3888 Fax: (318) 675-6867 EP Email: hcuell@lsuhsc.edu Running Head: Acute supratentorial ischemic stroke with ipsilateral hemiparesis AC C Key words: Stroke, supratentorial, hemiparesis, ipsilateral, thrombectomy, pathomechanism, Management Abstract word count: 210; Text word count: 1806; References: 17; Figures: 2 This article or any part of it has neither been published earlier nor been presented in any conference or seminar. We have not received any financial or other support from any source. There are no conflicts of interest with respect to this publication. ACCEPTED MANUSCRIPT P age |2 Acute Supratentorial Ischemic Stroke with Ipsilateral Hemiparesis: Pathomechanism and Management Challenges RI PT Abstract Introduction: Supratentorial stroke presenting as ipsilateral hemiparesis is rare. Multiple pathophysiological mechanisms are possible for this unusual phenomenon and has been previously described. However, its implication in therapeutic decision making in an acute emergency patient has never SC been discussed. We describe our experience with a patient with such unusual presentation where management decision was complex. M AN U Case Report: A 44 year old female presented with acute onset right hemiparesis and left facial weakness and evaluation with computed tomogram angiogram (CTA) showed right M3 segment occlusion. Her NIHSS score upon arrival was 9. To further clarify the situation, urgent magnetic resonance imaging was performed which showed ongoing ischemia in the right fronto-temporal cortex. Patient was taken for endovascular thrombectomy and complete revascularization was achieved. TE D Post operatively, patient completely improved neurologically. Further diffusion tractography imaging showed near complete non-decussation of corticospinal fibres. Conclusion: Discordance between clinical and initial CTA findings in an acute ischemic stroke patient poses EP a management challenge. Additional imaging to correlate clinical findings in equivocal cases may help in decision making, but may significantly delay intervention, and therefore its utility AC C during the short therapeutic window period needs careful consideration. Considering the risks and benefits ‘timely intervention’ should be balanced judiciously against ‘appropriate intervention’ to achieve a positive patient outcome. ACCEPTED MANUSCRIPT P age |3 Acute Supratentorial Ischemic Stroke with Ipsilateral Hemiparesis: Pathomechanism and Management Challenges Introduction: Sudden onset of unilateral limb weakness or facial droop represents the hallmark of acute RI PT supratentorial stroke and is attributed to ischemia or infarction of contralateral projection of corticospinal tracts supplying the ipsilateral face and limbs. However, hemiparesis due to the involvement of ipsilateral hemisphere is rare. In addition to a few prior individual case reports, the largest series has been reported by Inatomi et al., recently analyzing 14 such cases.1-12 All of SC the above studies have described patients with already developed ischemic stroke and have focused on their possible mechanism. However, its implication in an acute stroke patient with a M AN U potential for urgent therapeutic intervention has never been discussed. Such encounters are distinctly rare and present a great management dilemma in an emergency setting. We describe our experience with a patient with such unusual presentation where management decision for emergent thrombectomy was complex. We include a short review of literature for a better understanding of this phenomenon. Case Description: TE D A 44 year old left handed lady without any significant past medical history was brought to the emergency with acute onset of right sided hemiparesis and left facial weakness. The exact time of onset was uncertain but was less than 7 hours. Upon arrival the patient had right hemiparesis (MRC scale 3/5 in right upper and lower limbs) and the NIHSS score was 9. Urgent CT scan did EP not show any ischemic lesion. However, hyper dense MCA dot sign was evident in the right insular cistern (Figure 1A). Computed tomogram angiography (CTA) was done which showed AC C occlusion in one of the M3 branch of right MCA (Figure 1B). There was no evidence of any occlusion of any of the branches of left MCA or in the posterior circulation. In view of the discordance in the clinical and radiological findings, an urgent MRI with diffusion study was performed which showed a small focus of restricted diffusion in the right frontal cortex (Figure 1C). With the evidence of on-going ischemia in the ipsilateral cortex, we proceeded with urgent endovascular thrombectomy. On initial angiogram, there was a complete occlusion of the superior division of right M3 segment (Figure 1D). Successful thrombectomy using the 3Max aspiration catheter was done and a TICI 3 reperfusion was achieved (Figure 1E). Post thrombectomy, the patient improved completely in her neurological status. The post-operative ACCEPTED MANUSCRIPT P age |4 MRI did not show any infarct in the FLAIR images (Figure 1F). We performed the functional MRI with tractography which showed predominantly non-decussation of corticospinal tracts at the level of medulla (Figure 1G). The patient was discharged home on the third post-operative day without any residual deficit. RI PT Discussion: The organization of the cortical white matter fibres is highly complex especially when correlated with their functional laterality. Historically, anatomical studies have described a predominant contralateral innervation by the corticospinal tract and is due to decussation of the tract at the SC level of the medulla. However, further studies could demonstrate that a significant proportion of the fibres (nearly upto 30%) does not decussate and run in the ipsilateral spinal cord supplying the ipsilateral face and limbs.13 Some patients (especially with syndromic association) there is a M AN U high possibility of complete non-decussation of the fibers.4-6,9 Recent evidences suggest that the functional laterality of the corticospinal fibers are dynamic and change with time and bodily needs. Overall, multiple and possible overlapping mechanisms are possible to explain this rare expression of ipsilateral motor deficits caused by insult to corticospinal fibres in its supratentorial location. Inatomi et al have previously classified the patients into three groups TE D based on their possible pathomechanism.12 In this paper, we have added two another possibilities and have divided them into 5 groups as discussed below (Figure 2). Pathomechanism of ipsilateral motor deficit. (Figure 2) 1. Group A: Congenital non-decussation of fibres EP This the best possible explanation for an ipsilateral motor deficit but unfortunately have been documented in a small group of patients.2,4,6-9 Most of the patients with uncrossed fibres are associated with some form of congential abnormality including Dandy-Walker syndrome, AC C Joubert syndrome, Mobius syndrome, Occipital encephaloceles etc.4-6,9 However, nondecussation of fibres can occur sporadically and in normal individuals such as in our case. Although, our patient was left handed, it is still unclear whether dexterity has any association with decussation of fibres. 2. Group B: Predominant involvement of non-decussated fibres In humans, uncrossed fibers comprise a small yet significant proportion of the corticospinal tract that is also called as ventral corticospinal tract. The clinical significance of these fibres are rarely recognized, but at times a careful and detailed examination of an acute stroke patient reveal a ACCEPTED MANUSCRIPT P age |5 subtle weakness on the ipsilateral side. However, it is unclear if the uncrossed fibers can serve as the major supply to the ipsilateral limbs causing predominant ipsilateral hemiparesis. In one of the patient reported by Inatomi et al., the patient developed an acute stroke with ipsilateral hemiparesis and functional imaging showed contralateral activation of precentral gyrus RI PT suggesting crossed fiber anatomy.12 Such a case can only be explained by the selective involvement of uncrossed fibers of the ipsilateral side which are located closely but clearly separated from the crossed fibers. 3. Group C: Involvement of re-organized ipsilateral fibers: SC Although least understood, this is the most common proposed mechanism and involves the dynamic nature of the cortical fibers in their functional laterality.1,3,7,8,10-13 Almost all of the M AN U patients have a prior insult to the contralateral crossing fibers which with time recruits ipsilateral uncrossed fibers for the activity of the paretic limbs. Overtime, a lot of the function of the paretic limb is regained by predominant activity of ipsilateral uncrossed fibers. With the onset of the second insult which involves the ipsilateral uncrossed fibers results in worsening of the paresis in the ipsilateral side. 4. Group D: Involvement of ipsilateral fibres with double decussation: TE D This mechanism has not previously described in the patients with ipsilateral hemiparesis, although it represents similar non-decussation of fibres. Chang et al, have described a patient with schizencephaly, who presented with congenital hemiparesis and they found a group of neurons in the ipsilateral corticospinal tract which double decussated at the level of the brain EP stem.14 Although, the described patient did not have any stroke, our aim of discussing this patient is to have an understanding that double decussation although very rare but is possible and can AC C give rise to varying degree of clinical deficits when involved at different levels. 5: Group E: Involvement of supplemental motor areas: The organization of the supplemental motor areas and their functional significance is still not completely understood, however, many of the animal and human studies have confirmed their bilateral activity.15,16 Stimulation of these sites may evoke movement in all four limbs to variable extent and can be one of the possible mechanism for ipsilateral involvement. Lesions in the precentral insular cortex, cingulate sulcus, pre-frontal cortex are few sites which may give rise to such deficits. Although, none of the reported patients in the literature have clearly described this pathomechanism in their patients, one of the patients of Inatomi et al., with infarction near ACCEPTED MANUSCRIPT P age |6 cingulate gyrus and corpus callosum might have involved SMA giving rise to ipsilateral hemiparesis.12 Yamamoto et al. evaluated 12 patients with ataxic hemiparesis [AH] caused by lacunar infarct using SPECT perfusion imaging and attributed the incidence of ipsilateral ataxia in hemiparetic patients [with capsular infarct] to ipsilateral red nucleus dysfunction secondary to RI PT cortico-rubral pathway disruption at the internal capsule. They also noted the reduced ipsilateral red nucleus blood flow in AH patients and increased flow in pure motor hemiparesis patients.17 Encounter with ipsilateral ischemic stroke: Management challenges: Emergent endovascular thrombectomy has emerged as the gold standard intervention in acutely SC presenting ischemic stroke patients with large vessel occlusion (LVO). In stroke centers with thrombectomy capabilities, any acute ischemic stroke patient with focal deficits is immediately M AN U evaluated with CT angiogram to look for LVO on the contralateral side. Those patients with corroborating CT angiogram for LVO (occlusion contralateral to side of hemiparesis) or with negative CT angiogram fall into corresponding management plans, i.e urgent thrombectomy and medical management respectively. However, the situation is less straight forward when the CTA shows occlusion on the ipsilateral circulation. Such atypical patient have deficit ipsilateral to the occlusion seen in the initial angiogram without any evidence of infarct in the CT. In this context, TE D there are two possible explanations, one that the patient has one of the above described anatomical orientation of the fibres (figure2) with a true manifestation of the vessel occlusion, or else, the deficit is due to lacunar microembolic infarct to the contralateral side (which has not yet manifested in the CT scan) with an acute or chronic occlusion of the ipsilateral side which is EP asymptomatic (due to good collateral circulation). In the former situation, urgent thrombectomy is judiciously indicated whereas the latter situation can be managed conservatively. One AC C argument here is to take the patient for thrombectomy or thrombolysis directly irrespective of the side of occlusion. However, the benefits should be weighed against the risk associated with thrombectomy or thrombolysis in a patient with equivocal diagnosis. Our patient presented similarly, although one of her symptoms (left facial paresis) could be explained by the right MCA occlusion. We performed urgent MRI to correlate right MCA occlusion to the presence of any ongoing ischemia in that territory, and a positive correlation made our decision less ambiguous. However, usefulness of such ‘time-consuming’ imaging studies is questionable during the short therapeutic window period. While analyzing this case retrospectively, we feel an emergent thrombectomy was worthwhile and was duly indicated, as it is difficult to establish the ACCEPTED MANUSCRIPT P age |7 laterality of the white matter tracts in an acute patient who needs urgent intervention. Another important point that worth mentioning here is that, given the rarity of such occurrences, it is not unusual to miss an ipsilateral vessel occlusion when the smaller branches (M2, M3) are involved which can potentially be treated with thrombectomy. In most centres, pre-procedural RI PT tractography evaluation may not be feasible, like in our case. Therefore, one needs to have a high index of suspicion to look for any occlusion in the ipsilateral circulation when the contralateral circulation does not show any. Although, unusual anatomical configuration is possible sporadically, certain group of patients should be more carefully evaluated which includes encephaloceles and dandy-walker syndrome etc. M AN U Conclusion: SC patients with previous strokes, congenital anomalies like posterior fossa malformation, occipital Supratentorial stroke presenting as ipsilateral hemiparesis is rare. Confronting such a patient within the “window period” for thrombectomy in a level one stroke center may pose a management challenge. Additional imaging in equivocal cases may help in decision making but may significantly delay intervention, therefore its utility during the early therapeutic window period needs careful consideration. Considering the risks and benefits ‘timely intervention’ outcome. References 1. TE D should be balanced judiciously against ‘appropriate intervention’ to achieve a positive patient Ago T, Kitazono T, Ooboshi H, et al. Deterioration of pre-existing hemiparesis brought EP about by subsequent ipsilateral lacunar infarction. J Neurol Neurosurg Psychiatry. 2. Alurkar A, Sudha P Karanam L, Atre A, Nirhale S, Nayak S, Oak S. Ipsilateral stroke with 3. AC C 2003;74(8):1152-1153. uncrossed pyramidal tracts and underlying right internal carotid artery stenosis treated with percutaneous transluminal angioplasty and stenting. A rare case report and review of the literature. Neuroradiol J. 2012;25(2):237-242. Hebant B, Vaschalde Y, Cochin J-P, Hardy C, Lefaucheur R. Hemiparesis due to ipsilateral supratentorial stroke: Report of two cases. J Neurol Sci. 2016;365:121-123. 4. Hosokawa S, Tsuji S, Uozumi T, Matsunaga K, Toda K, Ota S. Ipsilateral hemiplegia caused by right internal capsule and thalamic hemorrhage: demonstration of predominant ipsilateral innervation of motor and sensory systems by MRI, MEP, and SEP. Neurology. ACCEPTED MANUSCRIPT P age |8 1996;46(4):1146-1149. 5. Kang K, Choi N-C. Ipsilateral hemiparesis and spontaneous horizontal nystagmus caused by middle cerebral artery territory infarct in a patient with agenesis of the corpus callosum. Neurol Sci. 2012;33(5):1165-1168. Ng ASL, Sitoh Y-Y, Zhao Y, Teng EWL, Tan EK, Tan LCS. Ipsilateral stroke in a patient RI PT 6. with horizontal gaze palsy with progressive scoliosis and a subcortical infarct. Stroke. 2011;42(1):e1-3. 7. Saada F, Antonios N. Existence of ipsilateral hemiparesis in ischemic and hemorrhagic 8. SC stroke: two case reports and review of the literature. Eur Neurol. 2014;71(1-2):25-31. Song Y-M, Lee J-Y, Park J-M, Yoon B-W, Roh J-K. Ipsilateral hemiparesis caused by a 2005;62(5):809-811. 9. M AN U corona radiata infarct after a previous stroke on the opposite side. Arch Neurol. Terakawa H, Abe K, Nakamura M, Okazaki T, Obashi J, Yanagihara T. Ipsilateral hemiparesis after putaminal hemorrhage due to uncrossed pyramidal tract. Neurology. 2000;54(9):1801-1805. 10. Xu Y, Liu L. Ipsilateral hemiparesis and contralateral lower limb paresis caused by 11. TE D anterior cerebral artery territory infarct. Neurosciences. July 2016:256-259. Yamamoto S, Takasawa M, Kajiyama K, Baron J-C, Yamaguchi T. Deterioration of hemiparesis after recurrent stroke in the unaffected hemisphere: Three further cases with possible interpretation. Cerebrovasc Dis. 2007;23(1):35-39. Inatomi Y, Nakajima M, Yonehara T, Ando Y. Ipsilateral hemiparesis in ischemic stroke EP 12. patients. Acta Neurol Scand. 2017;136(1):31-40. Kobayashi Z, Akaza M, Endo H, Numasawa Y, Tomimitsu H, Shintani S. Deterioration of AC C 13. pre-existing hemiparesis due to an ipsilateral internal capsule infarction after a contralateral stroke. J Neurol Sci. 2015;354(1-2):140-141. 14. Chang WH, Kim Y-B, Ohn SH, Park C-H, Kim ST, Kim Y-H. Double decussated ipsilateral corticospinal tract in schizencephaly. Neuroreport. 2009;20(16):1434-1438. 15. Kudo T, Uno T. Ipsilateral hemiparesis caused by subarachnoid hemorrhage in a patient with a ruptured middle cerebral artery aneurysm: a case report. Neurosurgery. 1984;15(5):727-729. 16. Schneider RC, Crosby E. Ipsilateral symptoms caused by an arteriovenous malformation ACCEPTED MANUSCRIPT P age |9 of the second or supplementary sensory area of the island of Reil. Neurosurgery. 1983;12(5):557-560. Yamamoto R, Johkura K, Nakae Y, Tanaka F. The mechanism of ipsilateral ataxia in EP TE D M AN U SC RI PT lacunar hemiparesis: SPECT perfusion imaging. Eur Neurol. 2015;73(1-2):106-111. AC C 17. ACCEPTED MANUSCRIPT Table 1: Summary of the literature on stroke with ipsilateral hemiparesis No of patients fMRI / DTT / Cortical mapping Stroke location Dominant hemisphere Group A Chronology of ipsilateral stroke Congenital Anomalies First Congenital scoliosis First Congenital scoliosis RI PT Authors, Year 1 Yes Internal capsule Left Terakawa et Al.9 [2000] 1 Yes putamen Ng et al.6 [2011] 1 Yes Putamen Left First Progressive scoliosis Kang and Choi.5 [2012] 1 Yes Putamen, NA Internal capsule First Corpus callosum agenesis Alurkar et al.2 2012 1 Corona radiata Left First None Present study 1 Cortical Right First None SC *Hosokawa et al.4 [1996] AC C EP Yes TE D M AN U Left Yes Group B ACCEPTED MANUSCRIPT 1 Yes Corona radiate, cortex NA Ago et al.1 [2003] 1 Yes Corona Radiata 2 Yes Corona radiata Yamamoto et al.11 [2007] 3 No Corona radiata-2 Thalamus-1 Saada et al.7 [2014] 2 No cortical Xu et al.10 [2016] 1 No - Second NA Second NA NA Second NA Left Second NA Cortical Left Second NA 2 No Internal capsule Right (1), NA (1) Second NA Second NA Kobayashi et al.13 [2015] 1 12 12 Inatomi et al. [2017] TE D EP AC C Hebant et al. [2016] No, MEP + Yes(9), No (3) Left M AN U Song et al.8 [2005] 3 NA SC Group C First RI PT Inatomi et al.12 [2017] Internal capsule NA various NA Second NA ACCEPTED MANUSCRIPT Group D 1 Yes NA - *Schneider et al.16 [1983] 1 No Cortical Left * 1 No Cortical SC Group E RI PT *Chang et al.14 [2009] NA M AN U Kudo et al.15 [1984] AC C EP TE D * Patients other than ischemic stroke, MEP- Motor evoked potential, NA- Not available NA Schizence phaly First NA First NA ACCEPTED MANUSCRIPT Legend to figures Figure 1: A: Initial CT head shows normal brain parenchyma without any ischemic signs. Hyperdense MCA sign is evident on the right insular cistern (white arrow) RI PT B: CTA at the time of admission shows occlusion at right M3 branch near insula (white arrow) C: Preoperative diffusion weighted MRI shows restricted diffusion in the right frontal cortex ( white arrow) corresponding to the site of vessel occlusion D: Catheter angiogram shows occlusion at the right M3 (yellow arrow) SC E: Angiographic run after thrombectomy shows TICI3 reperfusion (white arrow) F: Post-operative FLAIR sequence shows no infarct in the right frontal cortex that had restricted M AN U diffusion on the preoperative MRI G: Functional MRI with tractography shows near complete non-decussation of corticospinal fibers at the level of medulla (white arrow). Figure 2: Group A: Complete non-decussation of the corticospinal fibers. Stroke in the ipsilateral TE D hemisphere leads to hemiparesis on the same side. Group B: Predominant involvement of the non-decussated fibers or ipsilateral descending fibers form a major proportion of the corticospinal tract. Group C: Normal anatomical orientation of corticospinal fibers. Initial stroke on the EP contralateral side recruits ipsilateral fibers for the limb function over time. Subsequent stroke on the ipsilateral side involves these descending fibers causing ipsilateral hemiparesis. Group D: Double decussation of the corticospinal fibers at the level of brainstem. AC C Group E: Bilateral supply of supplementary motor cortex. AC C EP TE D M AN U SC RI PT ACCEPTED MANUSCRIPT AC C EP TE D M AN U SC RI PT ACCEPTED MANUSCRIPT ACCEPTED MANUSCRIPT Highlights of the Article • Supratentorial stroke presenting as ipsilateral hemiparesis is rare and has multiple pathophysiological mechanisms. Discordant imaging/ clinical findings in such cases creates management dilemma. • The ‘timely intervention’ vs ‘appropriate intervention’ needs to be balanced judiciously AC C EP TE D M AN U SC to achieve a positive patient outcome. RI PT • ACCEPTED MANUSCRIPT Abbreviations AH- Ataxic Hemiparesis • CTA- Computed Tomogram Angiogram • FLAIR-Fluid Attenuated Inversion Recovery • LVO-Large Vessel Occlusion. • MCA-Middle Cerebral Artery • MEP- Motor Evoked Potential • MRC Scale- Medical Research Council Scale • MRI- Magnetic resonance imaging • NIHSS-National Institute of Health Stroke Scale • SMA- Supplementary Motor Area • TICI score- Thrombolysis in Cerebral Infarction score AC C EP TE D M AN U SC RI PT • ACCEPTED MANUSCRIPT Disclosure – Conflict of Interest This article or any part of it has neither been published earlier nor been presented in any RI PT conference or seminar. Funding: We have not received any financial or other support from any source. Conflict of Interest: All authors certify that they have no affiliations with or involvement in any SC organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers, bureaus; membership, employment, consultancies, stock ownership, or M AN U other equity interest; and expert testimony or patent-licensing arrangements), or nonfinancial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the AC C EP TE D subject matter or materials discussed in this manuscript.