NEUROL-1852; No. of Pages 5 revue neurologique xxx (2017) xxx–xxx Available online at ScienceDirect www.sciencedirect.com Short communication Subacute corticobasal syndrome following internal carotid endarterectomy A. Marques a,b,*, N. Bourgois a, T. Vidal a,b,c, A. Ferrier a, S. Mathais a, C. Merlin c, C. Valla c, E. De Schlichting d, B. Jean e, D. Deffond c, F. Durif a,b a CHU Clermont-Ferrand, Neurology Department, 58 Rue Montalembert, 63003 Clermont-Ferrand, France University Clermont 1, UFR Medicine, EA 7980, 28 Place Henri Dunant, 63003 Clermont-Ferrand, France c CHU Clermont-Ferrand, Centre Mémoire de Ressources et de Recherche, 58 Rue Montalembert, 63003 ClermontFerrand, France d CHU Clermont-Ferrand, Neurosurgery Department, 58 Rue Montalembert, 63003 Clermont-Ferrand, France e CHU Clermont-Ferrand, Neuroradiology Department, 58 Rue Montalembert, 63003 Clermont-Ferrand, France b info article abstract Article history: The present report is of two patients who, immediately after internal carotid endarterec- Received 2 August 2016 tomy, presented with unexplained hemiplegia, despite normal findings on repeated MRI Received in revised form scans, which secondarily evolved into homolateral subacute corticobasal syndrome (CBS), 1st December 2016 with asymmetrical hemispheric hypometabolism and evidence of dopaminergic denerva- Accepted 15 June 2017 tion. This prompted us to propose an hypothesis of transient cerebral hypoxia arising during Available online xxx the surgical clamping period that might have provoked a prolonged or permanent functional lesion of the left hemisphere and basal ganglia, with no visible infarction on MRI but only Keywords: synaptic rearrangement of the neural networks, thereby revealing or exacerbating a poten- Corticobasal syndrome tially preexisting silent impairment. Dopaminergic degeneration # 2017 Elsevier Masson SAS. All rights reserved. Cerebrovascular disease Carotid endarterectomy Atypical parkinsonism 1. Introduction Corticobasal degeneration (CBD) is clinically characterized by a progressive asymmetrical presentation of limb rigidity or akinesia and apraxia, with other findings suggestive of additional basal ganglia and cortical dysfunction (such as dystonia, tremor, myoclonus, alien limb phenomena, cortical sensory deficit and/or impaired cognition) [1]. When first described, CBD was considered a distinct clinicopathological entity, but since then, it has been shown that, despite its many clinical diagnostic criteria, an ante-mortem diagnosis of CBD was pathologically confirmed in only 25–56% of cases, with other cases turning out to be progressive suprapranuclear * Corresponding author at: Neurology Department, CHRU Gabriel Montpied, 58, rue Montalembert, 63003 Clermont-Ferrand Cedex 1, France. E-mail address : ar_marques@chu-clermontferrand.fr (A. Marques). https://doi.org/10.1016/j.neurol.2017.06.017 0035-3787/# 2017 Elsevier Masson SAS. All rights reserved. Please cite this article in press as: Marques A, et al. Subacute corticobasal syndrome following internal carotid endarterectomy. Revue neurologique (2017), https://doi.org/10.1016/j.neurol.2017.06.017 NEUROL-1852; No. of Pages 5 2 revue neurologique xxx (2017) xxx–xxx palsy, frontotemporal dementia, Alzheimer’s disease or Parkinson’s disease [1,2]. These clinicopathological inconsistencies have led to the preferential use of the term ‘corticobasal syndrome’ (CBS) for the clinical presentation, while reserving the term CBD to describe the histopathology [1]. A few cases of CBS secondary to internal carotid artery (ICA) stenosis have recently been reported [3–5]. These vascular CBS cases presented with an insidious onset and gradual progression. Subacute CBS has previously so far only been described in cases of Creutzfeldt–Jakob disease [6]. Our present report is of two patients who, immediately after ICA endarterectomy, presented with unexplained hemiplegia, despite normal findings on repeated magnetic resonance imaging (MRI) scans, which secondarily evolved into homolateral subacute CBS. These cases were seen 1 year apart, and followed procedures undertaken by two different surgeons at two different institutions. 2. Observation Both these patients had a history of diabetes mellitus, hypertension and dyslipidemia. Patient 1 (P1; a 67-year-old left-handed male Caucasian) presented with an 80% right ICA stenosis and two episodes of transient amaurosis of the right eye, whereas Patient 2 (P2; a 71-year-old right-handed male Caucasian) was asymptomatic, but had a history of a stent for ischemic heart disease and a left middle cerebral artery stroke 7 years previously, with left ICA thrombosis (and persistent partial dysphasia), which led to the decision to perform a right carotid endarterectomy. Neither patient had a family history of movement disorders nor any reported bradykinesia prior to the surgery. Both procedures unfolded with no problems (each had a clamping period of 30 min and 38 min, respectively), yet both patients awoke from their operations with left-sided proportional hemiplegia. Angiography plus computed tomography (angio-CT) of both patients and CT perfusion scanning (P2 only, Fig. 1) performed immediately failed to reveal any abnormality in the right carotid field. There was also neither restenosis of the right ICA nor any stenosis of the other carotid axis, and the circle of Willis was complete with no hypoplasia. Yet, after 24 h and 72 h, both patients were still presenting with proportional left hemiplegia while angio-CT remained normal. When axial fluid-attenuated inversion recovery (FLAIR) and diffusion-weighted (DWI) MRI (1.5T, 5-mm slices) sequences were performed on day 6 (P1) and day 15 (P2), the scans revealed only mild atrophy and no infarcts in the right hemisphere. Left frontal hypersignalling compatible with vascular sequelae was identified in P2, whereas extremely sparse white-matter hyperintensities were noted in both patients (P1: Fazekas scale = 0; P2: Fazekas scale = 1; Fig. 2) [7]. When P1 underwent another MRI (3T) on day 20, it showed only scant hypersignalling in the periventricular white matter with no evidence of a recent stroke. While gradually recovering from the hemiplegia, P1 developed myoclonus on day 40 (video 1) whereas P2, on day 20, developed a tremor of the left superior limb (LSL) associated with rigidity and bradykinesia. The clinical evolution and investigations performed in both patients are summarized in Table 1. Neither patient presented with any clinical manifestations other that the ones described here. Neuropsychological assessment performed in P1 at 3 months revealed moderate left-sided apraxia (symbolic gestures), with preserved global cognitive functioning except for a mild episodic memory impairment, which was apparently present, according to the patient’s wife, before the endarterectomy. At 6 months after the surgery, an improvement in myoclonus and LSL dexterity was observed, although an akinetic-rigid syndrome persisted (video 1). After 9 months, a rapid cognitive decline of mainly dysexecutive symptoms was evident. Surprisingly, however, at the last assessment performed 20 months after endarterectomy, there was clear regression of the cognitive impairment in line with a global improvement reported by the patient. For P2, neuropsychological assessment at 3 months revealed anterograde verbal and visual memory impairment associated with a dysexecutive syndrome, and visuoconstructive apraxia and left-sided hemineglect. Another assessment conducted at 9 months found mostly praxis disorders involving the LSL (ideomotor and melokinetic apraxia; video 2), with no dysexecutive impairment, but an overall slowing of cognitive processing instead. Fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) identified, in both patients, severely decreased metabolism in the right frontoparietal area and right striatum (Fig. 2) which, in P2, was associated with milder decreased metabolism in the left frontal area, corresponding to a sequela of a previous stroke. Use of 123I-ioflupane (123I-FP-CIT, DaTscan, GE Healthcare, Chicago, IL, USA) showed, in both patients, reduced radioligand uptake in the right striatum, compatible with mild dopaminergic nigrostriatal presynaptic denervation in the right putamen (Fig. 2). Fig. 1 – Perfusion parameters on computed tomography (CT) of Patient 2: (A) mean cerebral blood volume (CBV; right: 2.54 mL/s/100 g; left: 3.93 mL/s/100 g); (B) mean maximum time (Tmax; right: 7.16 s; left: 7.93 s); and (C) mean transit time (MTT; right: 14.06 s; left: 15.57 s). Please cite this article in press as: Marques A, et al. Subacute corticobasal syndrome following internal carotid endarterectomy. Revue neurologique (2017), https://doi.org/10.1016/j.neurol.2017.06.017 NEUROL-1852; No. of Pages 5 revue neurologique xxx (2017) xxx–xxx 3 Fig. 2 – Structural and functional magnetic resonance imaging (MRI) findings in both Patient 1 (P1) and Patient 2 (P2): FLAIR and DWI sequences in P1 (A) and P2 (D); radiolabelling with 123I-FP-CIT in P1 (B) and P2 (E) shows reduced radioligand uptake in the right striatum; and 18F-FDG-PET in P1 (C) and P2 (F) shows decreased metabolism in the right hemisphere. Both patients were treated with levodopa (300 mg/day) but, in both cases, this treatment was electively discontinued (after 5 months in P1 and after 2 months in P2) because of a lack of clear benefit, according to them. In fact, P1 had improved with levodopa (less physical awkwardness and less myoclonus) before deciding to stop the treatment. Moreover, this recovery was maintained even after discontinuing the DOPA therapy. On the other hand, P2 experienced no benefit with levodopa. 3. Discussion Both of our patients, immediately after ICA endarterectomy, presented with unexplained hemiplegia, despite normal repeated MRI scans, which secondarily developed into homolateral subacute CBS, with asymmetrical hemispheric hypometabolism and evidence of dopaminergic denervation. While previous cases of patients with ICA stenosis and CBS have been reported, in those cases, unlike our present two patients, the CBS followed multiple infarcts with vascular lesions in the basal ganglia, as seen on MRI [3,4]. Whether the CBS in our patients was underpinned by a vascular or degenerative mechanism remains unclear. In addition, the fact that the immediate postoperative hemiplegia seen in our two patients persisted for several days with no ischemic signs on MRI, not even on diffusion sequences, is puzzling. It may be hypothesized that the hemiplegia, in the first place, and then the CBS might have been due to transient cerebral hypoxia arising during the surgical clamping period, which may have provoked a Please cite this article in press as: Marques A, et al. Subacute corticobasal syndrome following internal carotid endarterectomy. Revue neurologique (2017), https://doi.org/10.1016/j.neurol.2017.06.017 NEUROL-1852; No. of Pages 5 4 revue neurologique xxx (2017) xxx–xxx Table 1 – Chronological summary of clinical evolution and investigations carried out in two post-carotid-endarectomy patients. Patient 1 D0 D1 D3 D5 D6 D11 D15 D20 Cerebral CT, arteriography Cerebral, TSA CT Cerebral, TSA CT, CT perfusion Left hemiplegia Improvement of hemiplegia Cerebral, TSA CT Left hemiplegia MRI Holter EEG LIL recovery, LSL paresis MRI MRI D25 D40 M3 Patient 2 Left hemiplegia LSL tremor, akinetic-rigid syndrome, LIL recovery, LSL paresis Recovery from LSL paresis, persistent LSL tremor with akinetic-rigid syndrome, apraxia LSL myoclonus, akinetic-rigid syndrome, apraxia NPA, 18F-FDG-PET, 123 I-FP-CIT M6 M9 NPA M15 M20 MRI NPA NPA, 18F-FDG PET Improvement of myoclonus; recovery from LSL paresis, persistent akinetic-rigid syndrome, apraxia Rapid cognitive decline with mainly dysexecutive symptoms NPA, 123I-FP-CIT Cognitive improvement Day 0 (D0) for Patient 1 and Patient 2 are different as the two cases were separated by 1 year; CT: computed tomography; TSA: total surface area; MRI: magnetic resonance imaging; EEG: electroencephalography; LIL: left inferior limb; LSL: left superior limb; NPA: neuropsychological assessment; M: month; 18F-FDG-PET: fluorodeoxyglucose positron emission tomography; 123I-FP-CIT: 123I-ioflupane. prolonged or permanent functional lesion of the left hemisphere and basal ganglia, with no visible infarction on MRI, but only a synaptic rearrangement of the neural networks [8]. Some reports in the literature have suggested that the extent of vascular disease could contribute to an increased severity of clinical symptoms following transient ischemia, but that is unlikely to apply here as very sparse white-matter lesions were observed in our patients. Such a functional impairment with no anatomical lesion might be similar to what is observed in patients with post-anoxic dystonia or myoclonus, where MRI scans remain normal in the acute, subacute and even chronic phases [8,9]. It might also be hypothesized that hemiplegia with a normal CT scan may be due to a cerebral hyperperfusion syndrome (CHS), a rare condition that can arise after carotid endarterectomy [10]. While the pathophysiology is still not entirely clear, it is believed that dysregulation of the cerebrovascular system and hypertension together, resulting in an increase of cerebral blood flow, could potentially lead to brain injury. Interestingly, a CT scan in CHS can initially be normal, and focal deficits with no cytotoxic edema have previously been reported on diffusion MRI in this context. However, the findings may later develop into, for example, diffuse cerebral edema, patchy white-matter changes, mass effects and intracerebral hemorrhage. Such abnormalities, however, were not observed in our two patients. Moreover, CHS is generally clinically characterized by severe ipsilateral headache and seizures, which do not resemble any of the clinical manifestations presented by our patients, making the hypothesis of reperfusion-related injury unlikely. Nevertheless, the hypothesis of a preexisting silent neurodegenerative process revealed or exacerbated after transient ischemia during carotid endarterectomy and leading to CBS may feasibly be proposed. Interestingly, as P1 complained of episodic memory loss even before the surgery, it may be questioned whether chronic carotid stenosis might have played a role in the degenerative mechanism underlying a putative preexisting CBS. Indeed, It has been shown that cerebral hypoperfusion during carotid artery stenosis might lead to cognitive deficits independent of the white-matter lesion load [11]. Moreover, a patient with clinical manifestations of CBS (cognitive impairment and right-sided limbkinetic apraxia) beginning several months before the diagnosis of a left ICA occlusion, with decreased cerebral blood flow and atrophy with no infarction in the left hemisphere, has recently been reported [5]. However the improvement observed in our P1 is not compatible with a solely neurodegenerative process, but is suggestive of a reversible phenomenon resembling a more vascular-related mechanism. Disclosure of interest The authors declare that they have no competing interest. Appendix A. Supplementary data Supplementary data associated with this article can be found, in the online version, at https://doi.org/10.1016/j. neurol.2017.06.017. Please cite this article in press as: Marques A, et al. Subacute corticobasal syndrome following internal carotid endarterectomy. Revue neurologique (2017), https://doi.org/10.1016/j.neurol.2017.06.017 NEUROL-1852; No. of Pages 5 revue neurologique xxx (2017) xxx–xxx references [1] Boeve BF. The multiple phenotypes of corticobasal syndrome and corticobasal degeneration: implications for further study. J Mol Neurosci 2011;45:350–3. [2] Ling H, O’Sullivan SS, Holton JL, et al. Does corticobasal degeneration exist? A clinicopathological re-evaluation. Brain 2010;133:2045–57. [3] Engelen. et al. A 64-year old man presenting with carotid artery occlusion and corticobasal syndrome: a case report. J Med Case Rep 2011;5:357. [4] Kim YD, Kim JS, Lee ES, Yang DW, Lee KS, Kim YI. Progressive ‘‘vascular’’ corticobasal syndrome due to bilateral ischemic hemispheric lesions. Intern Med 2009;48:1699–702. [5] Miyaji Y, Koyama K, Kurokawa T, Mitomi M, Suzuki Y, Kuroiwa Y. Vascular corticobasal syndrome caused by unilateral internal carotid artery occlusion. J Stroke Cerebrovasc Dis 2013;22:1193–5. [6] Vandenberghe W, Sciot R, Demaerel P, Van Laere K. Sparing of the substantia nigra in sporadic Creutzfeldt–Jakob disease presenting as an acute corticobasal syndrome. Mov Disord 2007;22:1668–9. [7] Fazekas F, Chawluk JB, Alavi A, et al. MR signal abnormalities at 1.5 T in Alzheimer’s dementia and normal aging. AJR Am J Roentgenol 1987;149:351–6. [8] Ferlazzo E, Gasparini S, Cianci V, Cherubini A, Aguglia U. Serial MRI findings in brain anoxia leading to Lance–Adams syndrome: a case report. Neurol Sci 2013;34:2047–50. [9] Werhahn KJ, Brown P, Thompson PD, Marsden CD. The clinical features and prognosis of chronic posthypoxic myoclonus. Mov Disord 1997;12:216–20. [10] Farooq MU, Goshgarian C, Min J, Gorelick PB. Pathophysiology and management of reperfusion injury and hyperperfusion syndrome after carotid endarterectomy and carotid artery stenting. Exp Transl Stroke Med 2016;8:7. [11] Scherr M, Trinka E, Mc Coy M, Krenn Y, Staffen W, Kirschner M, et al. Cerebral hypoperfusion during carotid artery stenosis can lead to cognitive deficits that may be independent of white matter lesion load. Curr Neurovasc Res 2012;9:193–9. Please cite this article in press as: Marques A, et al. Subacute corticobasal syndrome following internal carotid endarterectomy. Revue neurologique (2017), https://doi.org/10.1016/j.neurol.2017.06.017 5