Hadas Stiebel-Kalish

Presentation, Natural History, and Management of Carotid Cavernous Aneurysms

OBJECTIVE:We present the largest reported cohort of carotid cavernous aneurysms (CCA), comparing the neuro-ophthalmic presentation, complications, and outcome with and without endovascular treatment. METHODS:Retrospective review of 185 patients with 206 CCAs examined between 1980 and 2001 at a tertiary neuro-ophthalmology and neurovascular service. Patients’ symptoms and findings at presentation were recorded and compared with those at outcome. The effect of treatment on outcome and on complication rate was analyzed using the &khgr;2 test, multivariate analysis of covariance, model-selection log-linear analysis, and multinomial logistic regression. RESULTS:Long-term follow-up was available for 189 of 206 CCAs. Seventy-four CCAs underwent treatment (endovascular, 67 [91%]; surgical treatment, 6 [9%]), and 115 were followed for an average of 4 years, two of which required later treatment. Treatment reduced the incidence and severity of pain, even after adjusting for the severity of initial pain (F(1,192 = 9.59, P = 0.002). Treatment did not significantly affect the patient’s final diplopia after adjusting for their initial diplopia (F(1, 182 = 2.01, P = 0.158). Statistical examination revealed that the treated group had a higher proportion of neurological and visual complications than people who were not treated (2(2). = 25.26, P = 0.0003). CONCLUSION:Endovascular treatment of carotid cavernous aneurysms leads to a significantly higher rate of pain resolution compared with untreated patients, even after adjusting for initial pain severity. Diplopia may not resolve after treatment. The results of this study underscore our approach indicating treatment only in cases of debilitating pain, visual loss from compression, or diplopia in primary gaze or in patients with risk factors for major complications such as pre-existing coagulopathy or sphenoid sinus erosion.

Cavernous sinus dural arteriovenous malformations: Patterns of venous drainage are related to clinical signs and symptoms

OBJECTIVE To provide evidence that venous congestion and drainage patterns are responsible for the manifestations of cavernous sinus area dural arteriovenous malformations (CSdAVMs). DESIGN Retrospective observational case series. PARTICIPANTS Records of 85 patients with complete clinical and angiographic evaluations of CSdAVMs were evaluated for the clinical features of the disorder. A neuroradiologist analyzed patterns of venous drainage to and from the cavernous sinus without knowledge of the clinical features. Four venous drainage patterns (reversal of flow from the CSdAVMs into the anterior cavernous sinus, ophthalmic vein thrombosis, drainage into the inferior petrosal sinus or drainage into the superior petrosal sinus) were statistically tested for their predictive value of signs and symptoms using logistic regression. MAIN OUTCOME MEASURES The power of prediction of orbital congestion, elevated IOP, extraocular muscle dysfunction, optic neuropathy, venous-stasis retinopathy, choroidal effusion, anterior chamber shallowing, bruits, cranial nerve paresis, and central nervous system dysfunction from four patterns of venous drainage. RESULTS Reversal of drainage into the anterior cavernous sinus and ophthalmic veins was highly predictive (P = 0) of orbital congestion, which was seen in 77 (91%) patients. In contrast, eight (9%) patients without orbital congestion had shunts that did not drain into the anterior cavernous sinus and ophthalmic veins. Cavernous sinus dural arteriovenous malformation drainage into the anterior cavernous sinus and ophthalmic veins also predicted elevated IOP (P = 0.0023) and optic neuropathy (P = 0.047). Ophthalmic vein thrombosis significantly predicted cases with choroidal effusion (P = 0.002) and anterior chamber shallowing (P = 0.01). Third nerve paresis could be predicted from flow toward the inferior petrosal sinuses (P = 0.017). Central nervous system symptoms or dysfunction, occurring in 7 (8%) patients, was predicted by venous drainage into the superior petrosal sinus (P = 0.0008). CONCLUSIONS The clinical features found in patients with CSdVAMs are related to the abnormal venous drainage and can be predicted by these venous drainage patterns. Venous congestion and hypertension seem to cause the clinical dysfunction in this disorder.

Cystoid macular edema after cataract surgery with intraocular vancomycin

OBJECTIVE To determine whether the use of supplemental prophylactic vancomycin in the irrigating solution during extracapsular lens extraction is associated with increased incidence of cystoid macular edema. DESIGN Prospective, randomized, double-masked clinical study. PARTICIPANTS Consecutive series of 118 patients 60 years of age or older undergoing cataract surgery. INTERVENTION The study group received an irrigating balanced salt solution supplemented with vancomycin (10 microg/ml), and the control group received the salt solution only. Fluorescein angiography was performed 1 and 4 months after surgery. MAIN OUTCOME MEASURES Evidence of angiographic and clinical cystoid macular edema, and visual acuity at 1 and 4 months after surgery. RESULTS The rate of postoperative angiographic cystoid macular edema was significantly higher in the study patients than in the control group at 1 month (55% vs. 19%, P = 0.0006) and 4 months (26% vs. 4%, P = 0.0099). The rates of clinical macular edema were 23% and 7%, respectively, at 1 month (P = 0.011) and 20% versus 0% at 4 months (P = 0.006). Visual acuity of 20/30 or better was noted at 4 months after surgery in 76% of the study group compared to 95.5% of the control group. CONCLUSIONS The role of preventive intracameral vancomycin during intraocular surgery should be reassessed in view of the associated increase in the incidence of angiographic cystoid macular edema.

Evolution of oculomotor nerve paresis after endovascular coiling of posterior communicating artery aneurysms: a neuro-ophthalmological perspective.

OBJECTIVEGuglielmi detachable coil treatment is becoming an accepted alternative to microsurgical clipping for select intracerebral aneurysms. Resolution of oculomotor nerve paresis (ONP) after endovascular packing was claimed to be complete in two prior series, with three and six cases. We describe the evolution of ONP after Guglielmi detachable coil treatment of posterior communicating artery aneurysms, and we search for endovascular and patient factors correlated with the degree of functional nerve recovery. METHODSTwelve cases of ONP attributable to posterior communicating artery aneurysms were treated with Guglielmi detachable coils between 1999 and 2002. Eleven patients were available for follow-up monitoring. The degree of ONP was recorded at admission, at discharge, after 3 months, and at yearly intervals thereafter. The size of the aneurysm, the duration of ONP before coiling, the degree of coiling, age, and the presence of other microvascular risk factors were correlated with the degree of nerve recovery. RESULTSComplete resolution of ONP did not occur in any of the 11 cases in this series. However, residual oculomotor nerve deficits did not cause diplopia with primary gaze for 10 of 11 patients. Clinically significant ptosis did not persist for any of the patients. The pupil remained minimally affected in all cases. CONCLUSIONAlthough mass effect remains after endovascular packing, oculomotor nerve dysfunction improves comparably to the recovery observed after surgical clipping. Contrary to previous reports, typical residual oculomotor nerve deficits persist. Older age and the presence of microvascular risk factors seem to be detrimental to ONP recovery.

The natural history of nontraumatic subarachnoid hemorrhage-related intraocular hemorrhages.

Purpose To describe the natural history of intraocular hemorrhages related to subarachnoid hemorrhage (SAH) as a result of ruptured intracranial aneurysms. Methods Retrospective review of patients with cerebral aneurysms examined by a referral neuro-ophthalmology service between 1980 and 1998. Patients with intraocular hemorrhages associated with SAH as a result of ruptured aneurysms were followed up without vitrectomy, unless bilateral vitreous hemorrhage occurred. Results Seventy of 450 patients with cerebral aneurysms had an SAH. Of these, 30 eyes of 19 patients had intraocular hemorrhages. Fourteen eyes had a vitreous hemorrhage; 12 had subhyaloid blood without a vitreous hemorrhage; and four had retinal hemorrhages alone. Two patients died shortly after presentation. Twenty-eight eyes were followed up for a mean of 4.8 years. Initial visual acuity was 20/100 to light perception in eyes with a vitreous hemorrhage, 20/20 to 20/400 in eyes with subhyaloid blood, and 20/20 to 20/40 in eyes with retinal hemorrhages. Three of the 12 eyes with a vitreous hemorrhage underwent vitrectomy. Of the nonoperated eyes, final visual acuity was at least 20/30 in 19 (76%) eyes, 20/40 to 20/60 in four (16%) eyes, and 20/100 in both eyes of one patient with premacular subhyaloid blood. None of the nonoperated eyes developed cataract formation or progression, retinal tears, or retinal detachment. Epiretinal membrane developed in one eye and pigmentary maculopathy developed in five. Conclusions Except for patients with bilateral vitreous hemorrhages, early vitrectomy may not be necessary in most cases of intraocular hemorrhages associated with nontraumatic SAH.

Mutations in TAX1BP3 Cause Dilated Cardiomyopathy with Septo‐Optic Dysplasia

We describe a Bedouin family with a novel autosomal recessive syndrome characterized by dilated cardiomyopathy and septo‐optic dysplasia. Genetic analysis revealed a homozygous missense mutation in TAX1BP3, which encodes a small PDZ domain containing protein implicated in regulation of the Wnt/β‐catenin signaling pathway, as the causative mutation. The mutation affects a conserved residue located at the core of TAX1BP3 binding pocket and is predicted to impair the nature of a crucial hydrophobic patch, thereby interrupting the structure and stability of the protein, and its ability to interact with other proteins. TAX1BP3 is highly expressed in heart and brain and consistent with the clinical findings observed in our patients; a knockdown of TAX1BP3 causes elongation defects, enlarged pericard, and enlarged head structures in zebrafish embryos. Thus, we describe a new genetic disorder that expands the monogenic cardiomyopathy disease spectrum and suggests that TAX1BP3 is essential for heart and brain development.

CSF pressure measurement during anesthesia: an unreliable technique

Background:  The measurement of cerebrospinal fluid (CSF) pressure is necessary for many clinical indications. Its accuracy may be compromized in frightened or uncooperative children who find it difficult to relax sufficiently. The aim of the present study was to evaluate possible effects of general anesthesia on CSF pressure values.

Gucy2f zebrafish knockdown - a model for Gucy2d-related leber congenital amaurosis

Mutations in retinal-specific guanylate cyclase (Gucy2d) are associated with Leber congenital amaurosis-1 (LCA1). Zebrafish offer unique advantages relative to rodents, including their excellent color vision, precocious retinal development, robust visual testing strategies, low cost, relatively easy transgenesis and shortened experimental times. In this study we will demonstrate the feasibility of using gene-targeting in the zebrafish as a model for the photoreceptor-specific GUCY2D-related LCA1, by reporting the visual phenotype and retinal histology resulting from Gucy2f knockdown. Gucy2f zebrafish LCA-orthologous cDNA was identified and isolated by PCR amplification. Its expression pattern was determined by whole-mount in-situ hybridization and its function was studied by gene knockdown using two different morpholino-modified oligos (MO), one that blocks translation of Gucy2f and one that blocks splicing of Gucy2f. Visual function was assessed with an optomotor assay on 6-days-post-fertilization larvae, and by analyzing changes in retinal histology. Gucy2f knockdown resulted in significantly lower vision as measured by the optomotor response compared with uninjected and control MO-injected zebrafish larvae. Histological changes in the Gucy2f-knockdown larvae included loss and shortening of cone and rod outer segments. A zebrafish model of Gucy2f-related LCA1 displays early visual dysfunction and photoreceptor layer dystrophy. This study serves as proof of concept for the use of zebrafish as a simple, inexpensive model with excellent vision on which further study of LCA-related genes is possible.

Digital red-free photography for the evaluation of retinal blood vessel displacement in epiretinal membrane

OBJECTIVE To evaluate the displacement of retinal blood vessels during the natural course of epiretinal membrane (ERM) formation. DESIGN Consecutive observational case series. PARTICIPANTS Thirteen patients (13 eyes) diagnosed with unilateral idiopathic ERM and 10 normal fellow eyes of the same patients served as a control group and constituted the study group. TESTING All eyes underwent digital red-free filter photography of the fundus using the Topcon Imagenet-1024 System. Photographs were taken on entry to the study and again after 8 to 13 months. Distances were measured between the major and minor blood vessel junctions at the upper and lower temporal arcades and between the disc margin and vessel junctions temporal to the macula on follow-up examinations. To clearly visualize vessel shift, both photographs of each patient were overlaid using the peripheral landmarks of major blood vessel crossings as reference points. MAIN OUTCOME MEASURES The parameters measured were shifting of blood vessels caused by the ERM formation. The distances were measured in micrometers using the measurement feature of the Topcon Imagenet System. RESULTS Blood vessel shift (range, 30 microm-434 microm) was noted in all 13 eyes, but in 15 measurements the shift was less than 30 microm and was considered as no shift. In four eyes (31%), the distances decreased in all directions, indicating contraction of the ERM. In four eyes (31%), the distances increased in all directions, indicating release of the ERMs. A mixed pattern of release and contraction of the ERM in the same eye was noted in five eyes (38%). No shift of blood vessels was noted in the control eyes. Findings on image overlay corresponded with the objective measurements. CONCLUSIONS Noninvasive digital red-free photography is an informative tool for the objective measurement of the vessel displacement during ERM formation. Contraction and release of the ERM were noted.

Visual Outcome in Meningiomas Around Anterior Visual Pathways Treated With Linear Accelerator Fractionated Stereotactic Radiotherapy

PURPOSE Meningiomas threatening the anterior visual pathways (AVPs) and not amenable for surgery are currently treated with multisession stereotactic radiotherapy. Stereotactic radiotherapy is available with a number of devices. The most ubiquitous include the gamma knife, CyberKnife, tomotherapy, and isocentric linear accelerator systems. The purpose of our study was to describe a case series of AVP meningiomas treated with linear accelerator fractionated stereotactic radiotherapy (FSRT) using the multiple, noncoplanar, dynamic conformal rotation paradigm and to compare the success and complication rates with those reported for other techniques. PATIENTS AND METHODS We included all patients with AVP meningiomas followed up at our neuro-ophthalmology unit for a minimum of 12 months after FSRT. We compared the details of the neuro-ophthalmologic examinations and tumor size before and after FSRT and at the end of follow-up. RESULTS Of 87 patients with AVP meningiomas, 17 had been referred for FSRT. Of the 17 patients, 16 completed >12 months of follow-up (mean 39). Of the 16 patients, 11 had undergone surgery before FSRT and 5 had undergone FSRT as first-line management. Tumor control was achieved in 14 of the 16 patients, with three meningiomas shrinking in size after RT. Two meningiomas progressed, one in an area that was outside the radiation field. The visual function had improved in 6 or stabilized in 8 of the 16 patients (88%) and worsened in 2 (12%). CONCLUSIONS Linear accelerator fractionated RT using the multiple noncoplanar dynamic rotation conformal paradigm can be offered to patients with meningiomas that threaten the anterior visual pathways as an adjunct to surgery or as first-line treatment, with results comparable to those reported for other stereotactic RT techniques.