Francesco Puccinelli

First-line intra-arterial versus intravenous chemotherapy in unilateral sporadic group D retinoblastoma: evidence of better visual outcomes, ocular survival and shorter time to success with intra-arterial delivery from retrospective review of 20 years of treatment

Purpose The introduction of intra-arterial chemotherapy (IAC) as salvage treatment has improved the prognosis for eye conservation in group D retinoblastoma. The aim of this study was to compare the outcomes of consecutive patients with advanced unilateral disease treated with either first-line intravenous chemotherapy (IVC) or first-line IAC. Design This is a retrospective mono-centric comparative review of consecutive patients. Patients Sporadic unilateral retinoblastoma group D cases treated conservatively at Jules-Gonin Eye Hospital and CHUV between 1997 and 2014. From January 1997 to August 2008, IVC, combined with focal treatments, was the primary treatment approach. From September 2008 to October 2014, IAC replaced IVC as first-line therapy. Methods 48 patients met the inclusion criteria, receiving only either IAC or IVC as primary treatment modality. Results Outcomes of 23 patients treated by IVC were compared with those of 25 treated by IAC; mean follow-up was 105.3 months (range 29.2–218.6) and 41.7 months (range 19.6–89.5), respectively. Treatment duration was significantly shorter in the IAC group (p<0.001). Ten eyes in the IVC group underwent enucleation. Recordable visual acuity of the salvaged eyes was significantly better in the IAC group (0.9 vs 1.4 logarithm of the minimum angle of resolution, p<0.01). No extraocular disease, metastases or long-term systemic complications were observed in either group. Conclusions The difference in the time frame between treatment groups had an impact on the availability of intravitreal chemotherapy treatment. Despite this, the results reported here imply that eyes treated with first-line IAC will have shorter treatment period, better ocular survival and visual acuity than first-line IVC.

Fornix infarction and Korsakoff dementia after coiling of a large anterior communicating artery aneurysm

Surgical occlusion of the anterior communicating artery (ACoA) can cause Korsakoff-like dementia, characterized by acute confusion, severe anterograde amnesia, and cognitive-behavioral changes, also known as the ACoA syndrome (ACoAS).1 Surprisingly, this usually does not occur after deliberate endovascular ACoA occlusion, which is occasionally performed to reduce the high recurrence rate of broad-based ACoA aneurysms treated by coiling.2 We present a case of bilateral fornix infarction and Korsakoff dementia after coil embolization and parent vessel occlusion of a large ACoA aneurysm. We emphasize the underlying anatomy of a poorly known perforator, the subcallosal artery (SubCA).

Factors Associated With Focal Computed Tomographic Perfusion Abnormalities in Supratentorial Transient Ischemic Attacks

Background and Purpose— Computed tomographic perfusion (CTP) is useful in diagnosis of patients with transient focal neurological symptoms. In acute imaging of patients with a suspected transient ischemic attack (TIA), it remains unclear which patients develop focal perfusion abnormalities (FPA), that is, hypoperfusion or hyperperfusion. We aimed at determining independent factors associated with FPA in patients with supratentorial TIAs. Methods— We prospectively collected consecutive patients with supratentorial TIAs defined by the traditional time-based definition who underwent CTP within 24 hours of symptom onset. We recorded demographics, risk factors, clinical features, severity, and timing from onset. We documented the Age, Blood Pressure, Clinical Features, Duration, and Diabetes (ABCD2) scores, vascular territories, and presence of relevant arterial pathology. Variables were tested for an association with FPA with univariate and multivariate analyses. Results— A hundred and ten of 265 patients (42%) with supratentorial TIAs had FPA on CTP. Acute noncontrast computed tomography showed early ischemic lesions in 6%, and acute/subacute magnetic resonance imaging was pathological in 52 of the 109 cases (47.7%) where it was performed. Clinical factors associated with FPA were high-admission National Institutes of Health Stroke Scale (odds ratio [OR], 1.22), right hemispheric TIA (OR, 3.09), and cardioembolic mechanism (OR, 2.19). Persistence of symptoms during CTP (OR, 2.59), shorter duration of TIA (OR, 0.93), major intracranial arterial pathology (OR, 12.5), and extracranial arterial occlusion (OR, 7.44) were also associated with FPA. Conclusions— Supratentorial TIAs are often associated with FPA in CTP, even after symptom resolution. FPAs are frequent in severe TIAs and those associated with cardioembolism or specific arterial pathologies. These findings can help clinicians in accurate diagnosis of TIA and its underlying mechanisms.

Diagnosis and management of secondary epipapillary retinoblastoma

Background Reports on retinoblastoma relapse at the optic nerve head (ONH) are anecdotal and include only treatments by external beam radiotherapy (EBRT) or enucleation. We aimed to describe such cases, termed secondary epipapillary retinoblastoma, diagnosed and monitored with the assistance of hand-held spectral domain optical coherence tomography (HHSD-OCT) and treated with intraophthalmic artery chemotherapy (IAC) and/or intravitreous chemotherapy (IViC). Methods A retrospective analysis of secondary epipapillary retinoblastoma cases treated conservatively. Results Four males and two females were included, diagnosed with secondary epipapillary retinoblastoma at a median time of 8.6 months (mean 24.0) from initial retinoblastoma diagnosis. HHSD-OCT was used in all cases for accurate diagnosis; in 2/6, the epipapillary relapse was detected only by means of HHSD-OCT. Treatments for secondary epipapillary retinoblastoma included IAC and IViC (n=4), IAC alone (n=1) and IViC alone (n=1). HHSD-OCT demonstrated complete epipapillary tumour regression in all cases, achieved in a median time of 1.6 months (mean 1.8). The median time from secondary epipapillary retinoblastoma resolution to last visit was 29.2 months (mean 27.5). At last visit, all eyes were tumour-free and no cases of metastasis recorded. Conclusions Cases of retinoblastoma relapse at the ONH show common clinical features and represent specific diagnostic and therapeutic challenge; hence, we propose to consider this condition as a subset of retinoblastoma, termed secondary epipapillary retinoblastoma. HHSD-OCT is an invaluable diagnostic tool in the initial diagnosis as well as in monitoring these lesions, and IAC and IViC are efficient modalities for this clinical scenario, obviating the need for EBRT or enucleation.

Successful conservative treatment of massive choroidal relapse in 2 retinoblastoma patients monitored by ultrasound biomicroscopy and/or spectral domain optic coherence tomography

ABSTRACT Purpose: To report the occurrence and management of secondary choroidal infiltration in two retinoblastoma (rb) patients. Methods: Fundus examination and imaging with spectral domain optical coherence tomography (SD-OCT), B-scan ultrasonography (B-scan), and ultrasound biomicroscopy (UBM). Results: Case 1: A 19-month-old girl with multifocal unilateral group B rb pretreated with intravenous chemotherapy (IVC) was referred for further management. At 3.5 years of age, routine 3-Tesla magnetic resonance imaging (3T-MRI) revealed an asymptomatic pinealoblastoma that underwent resection and adjuvant intensive IVC. Concomitant ophthalmic follow-up revealed a recurrence 8.3 × 2.8 mm at the posterior pole nasally to the optic disc on B-scan, localized within the choroid on SD-OCT and 3T-MRI. With high dose IVC ongoing, total regression of the choroidal mass was confirmed on SD-OCT already after 3 weeks. At 6-month follow-up, choroidal and pineal tumors were in complete remission. Sadly, the child died of intravascular disseminated coagulation-like disease after the 5th IVC. Case 2: A heavily pretreated 20-month-old girl with bilateral rb was referred for persistent vitreous seeding in her remaining eye (OD). Three months after intravitreal chemotherapy and chemothermotherapy, a hemorrhagic mass was observed inferior to the primary tumor. Two weeks later, an underlying peripheral choroidal mass 16 × 6 mm was documented by UBM and confirmed by 3T-MRI. Complete resolution was achieved 3 weeks after combined intra-arterial chemotherapy (IAC) of melphalan-topotecan. No recurrence or metastasis was observed at 34-month follow-up. Conclusion: Isolated massive choroidal invasion can be treated conservatively with IVC or IAC in selected cases. SD-OCT, UBM, and B-scan ultrasonography are instrumental in the detection and follow-up of choroidal lesions.

Letter to the Editor. Clipping after Pipeline embolization device placement for a thrombosed ACoA aneurysm

TO THE EDITOR: We read with great interest the article published by Daou and colleagues2 (Daou B, Chalouhi N, Starke RM, et al: Clipping of previously coiled cerebral aneurysms: efficacy, safety, and predictors in a cohort of 111 patients. J Neurosurg 125:1337–1343, December 2016). This publication has enormous interest for cerebrovascular neurosurgeons working in centers that offer both endovascular and surgical aneurysm repair strategies. Surgical treatment of aneurysms previously treated with endovascular therapy presents several constraints, as mentioned in this article. We would like to provide from our practice an additional example of clipping an aneurysm that had been previously treated with a stent as we think it would be interesting to readers of the cited article. While ruling out causes of chronic headache, we diagnosed a 70-year-old woman with an aneurysm of the anterior communicating artery (ACoA), with its neck at the left A1–A2 junction. The aneurysm measured 8 × 8.5 mm. The dome of the aneurysm was pointing anteroinferiorly and had an intraluminal thrombus (Fig. 1). She had no visual or other neurological deficits associated with the aneurysm. Considering the size and location of the aneurysm, our multidisciplinary team proposed treatment. Both surgical and endovascular options were suggested, and the patient elected to undergo the endovascular option. A 2.75 × 16–mm Pipeline embolization device (PED) was positioned on the left A1–A2 segments under biplane fluoroscopic guidance. The immediate postprocedural digital subtraction angiography (DSA) study showed marked contrast stasis within the sac, compatible with reduced inflow. Treatment with aspirin and clopidogrel had been instituted 1 week before the procedure, without any antiplatelet resistance on biological tests. Magnetic resonance angiography (MRA) performed 1 month after treatment showed no evidence of blood flow inside the aneurysm sac, and the patient had a normal neurological examination. Three months after intervention, the patient experienced progressive diminution of vision in the left eye, and in the space of a week she had no light perception in this eye. Visual field and optical coherence tomography (OCT) findings suggested a lesion of the retrobulbar, prechiasmatic optic nerve on the left side (Fig. 2A and C). Magnetic resonance imaging, MRA, and DSA showed complete exclusion of the treated aneurysm and normal flow within the parent vessel but also a paradoxical increase in size related to intrasacular thrombosis, leading to worsening of the mass effect and optic neuropathy (Fig. 3). After discussion in the multidisciplinary neurovascular board, we elected to treat this aneurysm surgically. The optic nerve was markedly compressed by a turgid thrombosed aneurysm with solid and liquid components. The thrombosed aneurysm sac was excised after decompression of the sac contents, and the aneurysm neck was clipped. The aneuysm sac was completely dissected away from the optic nerve, thus achieving good decompression of the nerve (Fig. 4). The patient recovered her vision completely in the first 2 postoperative days, which was later confirmed with formal assesments of visual acuity, fields, and OCT (Fig. 2B and D). As Colby and colleagues recently showed in a nonrandomized retrospective series,1 flow diversion using a PED for the repair of an ACoA aneurysm seems to have an extremely high rate of success (96%) immediately after the procedure. With respect to long-term results, this study showed complete occlusion of the aneurysm in 86% at an average follow-up of 10.4 months. The safety and efficacy of PED placement in terms of ophthalmological outcome after coiling large and giant internal carotid artery aneurysms were evaluated by Sahlein et al.4 while analyzing the results of the Pipeline for Uncoilable or Failed Aneurysms (PUFS) trial. These authors found that the procedure was related to a 5% worsening of previous ophthalmological deficit, attributed to ischemia of the ophthalmic artery territory. Gressot et al.3 have recently shown that

Response to Khetan and Maitray’s “Comment: Conservative management of massive choroidal relapse in retinoblastoma patients?”

We would like to thank Khetan and Maitray for their interest in our publication entitled “Successful conservative management of massive choroidal relapse in 2 retinoblastoma patients monitored by ultrasound biomicroscopy and/or spectral domain optic coherence tomography” (1). The authors raised a few discussion points that we would like to comment on. The authors ask if the child in case 1, who suffered unilateral retinoblastoma and developed pinealoblastoma had genetic testing performed, that could have led to MRI screening and early detection of pinealoblastoma. RB1 gene sequencing had been performed but failed to reveal a germline mutation. Despite that, the child was undergoing routine screening brain MRI for early diagnosis of pinealoblastoma, as she was suffering unilateral bifocal retinoblastoma, which allowed us, as mentioned in the manuscript, to diagnose an asymptomatic pineal mass. The authors query if the time of subclinical signs of choroidal invasion coincided with the time of starting intensive adjuvant chemotherapy for pinealoblastoma, and if the choroidal relapse grew while the child had started adjuvant chemotherapy. The answer is no. Diagnosis of the pinealoblastoma was only made definitively after a second biopsy, coinciding with the observation of the choroidal recurrence, and treatment was initiated at this point. The authors suggest that massive choroidal invasion such as the one observed in case 1 should better be treated with enucleation and adjuvant chemotherapy especially, because the lesion was seen to be abutting the optic nerve on ultrasonography. First of all, the concern regarding the optic nerve involvement was not supported by B-scan, SD-OCT, and 3-Tesla MRI imaging. On the other hand, the presence of a concomitant pinealoblastoma prioritized intensive systemic chemotherapy over secondary enucleation, which was only postponed at this time. The authors suggest that the choroidal lesion of case 2 could have been already clinically detected in the fundus image at the visit at which the vitreous hemorrhage was first noticed, possibly with dilated surface blood vessels. At that point though, there was no ophthalmoscopic evidence of any choroidal mass or vascular abnormalities as confirmed by fluorescein angiogram (data not shown). The authors also ask why we waited 2 weeks to perform ultrasonography and MRI and state that UBM is not an appropriate tool to assess and measure suspected choroidal lesion with posterior extent close to the equator. As mentioned in the text, ultrasonography was performed when vitreous bleeding at 6 o’clock was observed for the first time, showing an elevated lesion. The diagnosis of a choroidal mass could not have been made even in retrospect on those images, because the lesion was small and lying very anteriorly, subject to ultrasonographic artefacts. Although we agree that UBM is not useful for retro-equatorial imaging, it is perfectly suited to assess pre-equatorial pathologies, including choroidal tumors, provided that the globe is appropriately rotated. Finally, as the post cryotherapy vitreous bleeding was not covering the optic nerve, a 2-week follow-up interval was indicated, especially given the absence of any associated abnormalities. The authors conclude their letter with the controversy regarding the need for adjuvant chemotherapy in case of isolated massive choroidal invasion, an issue already debated in our article. We acknowledge their concerns and emphasize that the decision to give or not systemic chemotherapy should be submitted to the institutional tumor board and discussed with the family.

Endovascular therapy versus intravenous thrombolysis in cervical artery dissection ischemic stroke – Results from the SWISS registry:

Introduction In patients with stroke attributable to cervical artery dissection, we compared endovascular therapy to intravenous thrombolysis regarding three-month outcome, recanalisation and complications. Materials and methods In a multicentre intravenous thrombolysis/endovascular therapy-register-based cohort study, all consecutive cervical artery dissection patients with intracranial artery occlusion treated within 6 h were eligible for analysis. Endovascular therapy patients (with or without prior intravenous thrombolysis) were compared to intravenous thrombolysis patients regarding (i) excellent three-month outcome (modified Rankin Scale score 0–1), (ii) symptomatic intracranial haemorrhage, (iii) recanalisation of the occluded intracranial artery and (iv) death. Upon a systematic literature review, we performed a meta-analysis comparing endovascular therapy to intravenous thrombolysis in cervical artery dissection patients regarding three-month outcome using a random-effects Mantel–Haenszel model. Results Among 62 cervical artery dissection patients (median age 48.8 years), 24 received intravenous thrombolysis and 38 received endovascular therapy. Excellent three-month outcome occurred in 23.7% endovascular therapy and 20.8% with intravenous thrombolysis patients. Symptomatic intracranial haemorrhage occurred solely among endovascular therapy patients (5/38 patients, 13.2%) while four (80%) of these patients had bridging therapy; 6/38 endovascular therapy and 0/24 intravenous thrombolysis patients died. Four of these 6 endovascular therapy patients had bridging therapy. Recanalisation was achieved in 84.2% endovascular therapy patients and 66.7% intravenous thrombolysis patients (odds ratio 3.2, 95% confidence interval [0.9–11.38]). Sensitivity analyses in a subgroup treated within 4.5 h revealed a higher recanalisation rate among endovascular therapy patients (odds ratio 3.87, 95% confidence interval [1.00–14.95]), but no change in the key clinical findings. In a meta-analysis across eight studies (n = 212 patients), cervical artery dissection patients (110 intravenous thrombolysis and 102 endovascular therapy) showed identical odds for favourable outcome (odds ratio 0.97, 95% confidence interval [0.38–2.44]) among endovascular therapy patients and intravenous thrombolysis patients. Discussion and Conclusion In this cohort study, there was no clear signal of superiority of endovascular therapy over intravenous thrombolysis in cervical artery dissection patients, which – given the limitation of our sample size – does not prove that endovascular therapy in these patients cannot be superior in future studies. The observation that symptomatic intracranial haemorrhage and deaths in the endovascular therapy group occurred predominantly in bridging patients requires further investigation.

Conservative treatment of diffuse infiltrating retinoblastoma: optical coherence tomography-assisted diagnosis and follow-up in three consecutive cases

Background/aims To report conservative therapy in diffuse infiltrating retinoblastoma (DIR) and describe specific optic coherence tomography (OCT) features of the tumour. Methods Retrospective review of all DIR cases treated conservatively between 1998 and 2012. Results Three patients (three eyes) were included, cases 1 and 3 with previous enucleation of the contralateral eye and case 2 with unilateral retinoblastoma referred after prior pars plana vitrectomy with silicone oil. Mean age at diagnosis was 7 years (range 14 months–14 years). Globe and vision preservation (Snellen visual acuity of 12.5/10) was achieved in case 3 with a recurrence-free follow-up of 33 months after first-line thermotherapy followed by salvage intra-arterial chemotherapy (IAC) plus focal treatments. Cases 1 and 2 were enucleated for progressive disease, case 1 after first-line intravenous chemotherapy (IVC) consolidated by focal therapies and salvage treatments given over 8 years of partial remission and case 2 after IAC, brachytherapy and intracameral chemotherapy. Neither showed any high-risk histopathological features, and no adjuvant chemotherapy was necessary. Both patients are alive without metastasis (mean follow-up of >10 years). Pathognomonic features of the tumour were revealed by OCT in all cases, showing infiltration of the ganglion cell layer and horizontal growth over the inner plexiform layer. Complete restoration of the retinal microanatomy was documented after retraction of the tumour following IVC in case 2 and IAC in case 3. Conclusion This is the first report of successful conservative management in DIR. OCT enabled diagnosis, delimitation of the tumour margins and monitoring of the treatment response in this context.

Balloon-assisted coil embolization and large stent delivery for cerebral aneurysms with a new generation of dual lumen balloons (Copernic 2L)

Introduction Dual coaxial lumen balloon microcatheters through which small stents can be delivered have recently been described. We report a series of a new type of dual lumen balloon catheter with a parallel lumen design enabling enhanced inflation and deflation properties through which larger stents may be deployed, including flow diverters (FD). Methods All aneurysms that were treated with a Copernic 2L (COP2L) dual lumen balloon catheter at our institution between February 2014 and December 2016 were assessed. Patient demographics, aneurysm characteristics, clinical and angiographic follow-up, as well as adverse events were analyzed. Results A total of 18 aneurysms in 16 patients (14 women) were treated with the COP2L. Mean maximal aneurysm diameter was 6.4 mm, mean neck size was 3.3 mm (min 1; max 6.3), and mean aneurysm height/width was 1.1 (min 0.5; max 2.1). The COP2L was used for balloon-remodeled coiling exclusively in 2 aneurysms; coiling and FD stenting in 8; coiling and braided stent delivery in 3; coiling, braided and FD stenting in 1; and FD stenting without coiling in 4 (stenting alone). The rate of Roy–Raymond 1 (complete occlusion) changed from 22% in the immediate postoperative period to 100% at 3 months (mean imaging follow-up 8.2 months). There were three technical complications (3/16, 18.7%), including a perforation and two thromboembolic asymptomatic events that were rapidly controlled with the COP2L. There was no immediate or delayed morbidity or mortality (modified Rankin Scale score 0–1 in 100% of patients). Conclusion The COP2L is a new type of dual lumen balloon catheter that may be useful for balloon and/or stent-assisted coiling of cerebral aneurysms. The same device can be used to deliver stents up to 4.5 mm and to optimize stent/wall apposition or serve as a life-saving tool in case of thromboembolic or hemorrhagic events. Long-term efficacy and safety need to be further assessed with larger case-controlled cohorts.