Optic Sheath Research Articles

Management of surgical clinoidal meningiomas

Clinoidal meningiomas remain a major neurosurgical challenge. Surgery-related outcome has been less than desirable in the past, and little attention has been directed toward improving visual deficits. The authors advocate a skull base technique for the removal of these difficult tumors and describe its advantages in terms of improving extent of resection and enhancing overall outcome, particularly visual function. A retrospective analysis was performed on data obtained in 26 consecutive patients with clinoidal meningiomas (including one patient with hemangiopericytoma) who underwent resection between June 1995 and January 2003. In 24 cases the skull base procedure involved extradural anterior clinoidectomy, optic canal unroofing, and optic sheath opening; in two cases a standard pterional craniotomy was performed. Fourteen of the 26 patients suffered significant preoperative visual deficits. All patients underwent thorough pre- and postoperative ophthalmological evaluations. The follow-up period ranged from 3 to 91 months (mean 42.3 months). Total resection was achieved in 20 patients (77%), and the majority (76.9%) of patients with preoperative visual impairment experienced significant improvement. With the use of the skull base technique, total resection and excellent visual outcome may be achieved with minimal morbidity in most patients with clinoidal meningiomas.

Surgical management of clinoidal meningiomas.

Surgical outcome has been less than desirable in the management of patients with clinoidal meningiomas in the past, and little attention has been directed at improving their visual function. The purpose of this article is to advocate an available cranial base technique for removing these difficult tumors and to delineate the technique's advantages that aid in achieving an improved extent of tumor resection and enhancing the patients' overall outcome, particularly their visual outcome. A retrospective analysis was performed on 15 consecutive patients with clinoidal meningiomas (including a patient with hemangiopericytoma) who underwent surgical resection at the Cleveland Clinic Foundation between June 1995 and January 2000. A cranial base technique consisting of extradural anterior clinoidectomy, coupled with optic canal unroofing and optic sheath opening, was used in 13 patients, and standard pterional craniotomy was used in 2. Eight of 15 patients had significant visual deficits preoperatively. All patients had thorough preoperative and postoperative ophthalmological evaluations. The follow-up period ranged from 6 to 60 months (mean, 37.2 mo). Total resection was achieved in 13 (86.7%) of the 15 patients in this series, and the majority of the patients with preoperative visual impairment experienced significant improvement (6 of 8 patients; 75%). In the majority of patients with clinoidal meningiomas, total resection may be achieved with minimal complications. For large tumors encasing the optic nerve and internal carotid artery, or for those tumors causing preoperative visual impairment, use of the cranial base technique delineated in this study may lead to significant improvement in the patients' visual and overall outcomes.

Protective Effects of Selectin Ligands/Inhibitor (SKK-60060) against Retinal Ischemia-Reperfusion Injury

A newly developed selectin ligand inhibitor (SKK-60060) has been shown to block P- and L-selectins in vitro. We examined its inhibition of leukocyte–endothelial interactions in vivo against retinal ischemia-reperfusion injury and protective effects on ischemia-induced retinal damage.Retinal ischemia was induced by temporary ligation of the optic sheath for 60min in anesthetized pigmented rats. SKK-60060 was administered 5min before reperfusion and 4, 12, 24 and 48hr thereafter, and leukocyte dynamics in the retinal microcirculation were evaluated using acridine orange digital fluorography. After 7 days of reperfusion, ischemia-induced retinal damage was also assessed histologically.SKK-60060 treatment suppressed leukocyte rolling during the reperfusion period; their numbers in the SKK-60060-treated rats were reduced by 67.0% (P<0.01) and 53.2% (P<0.01) at 12 and 24hr, respectively. The subsequent leukocyte accumulation was also inhibited in SKK-60060-treated rats; accumulated leukocytes in the SKK-60060-treated rats were reduced by 72.8% (P<0.01) and 53.4% (P<0.01) at 12 and 24hr, respectively. Retinal venous vasodilation in SKK-60060-treated rats were significantly suppressed at each time point (P<0.05). Histological examination demonstrated protective effects of SKK-60060 on ischemia-induced retinal damage, which were more substantial in the inner retina (P<0.01).SKK-60060 significantly inhibits the leukocyte rolling along the major retinal veins and their accumulation during the reperfusion period. These results suggest therapeutic potential of SKK-60060 for ischemia-reperfusion injury.

Intensity modulated conformal therapy for intracranial lesions

The Peacock planning and delivery system was used to create treatment plans and deliver these plans to patients. The system involves an arc therapy delivery of small (2 cm long) slices of radiation combined with indexing of the couch to achieve target coverage. Two clinical examples are shown to demonstrate the system’s capability and evaluate the resources required to produce and deliver the plans. One plan is an optic sheath meningioma and the other is a craniopharyngioma that surrounded the optic chiasm. The optic sheath meningioma was treated to 50 Gy in 25 fractions. The treatment involved delivery of two arcs. The total time to set up the patient and deliver the treatment was less than 15 min. Planning and plan validation after computed tomography required approximately 3 days. The patient had 100% restoration of her field of vision and is stable 3 years post therapy. The second patient is a 9-year-old who had a craniopharyngioma which surrounded the optic chiasm. The tumor was treated to 50.4 Gy in 28 fractions and the dose to the optic chiasm was limited to 45 Gy. The treatment required three arcs and total treatment time was less than 20 min. The patient is stable 15 months post therapy. The system is able to create and deliver radiation patterns that are unique. These plans can be created and delivered in times that rival conventional forward planning conformal radiotherapy systems that cannot produce or conveniently deliver such plans.

Tacrolimus (FK506) Attenuates Leukocyte Accumulation After Transient Retinal Ischemia

Tacrolimus, an immunosuppressant agent, has been shown to reduce tissue injury and leukocyte accumulation after transient ischemia. This study was designed to evaluate quantitatively the inhibitory effects of tacrolimus on leukocyte rolling and on subsequent leukocyte accumulation in vivo after transient retinal ischemia and the protective effects of tacrolimus on ischemia-induced neural damage. Retinal ischemia was induced for 60 minutes in anesthetized pigmented rats by temporary ligation of the optic sheath. Tacrolimus was administered at 10 minutes after ischemic induction. At 4, 12, 24, and 48 hours after reperfusion, leukocyte behavior in the retinal microcirculation was evaluated in vivo with acridine orange digital fluorography. After 7 days of reperfusion, ischemia-induced retinal damage was evaluated histologically. Treatment with tacrolimus suppressed leukocyte rolling; the maximum number of rolling leukocytes was reduced by 60.1% at 12 hours after reperfusion (P<0.05). In tacrolimus-treated rats, the velocity of rolling leukocytes was significantly faster than in vehicle-treated rats (P<0.01). The subsequent leukocyte accumulation was reduced by 61.6% at 24 hours after reperfusion (P<0.01). Histological examination demonstrated the protective effect of tacrolimus on ischemia-induced retinal damage, which was more substantial in the inner retina (P<0.01). The present study demonstrated the inhibitory effect of tacrolimus on leukocyte rolling and on subsequent leukocyte accumulation and the therapeutic potency to neural injury after transient retinal ischemia.

Terson??s Syndrome in Subarachnoid Hemorrhage

Manuscript received November 20. 1997: accepted Februap 20, 1998. From the Department of Ophthalmology (A.M.F.W.. W-C.L.) and the Seuro-ophthalmology Unit (J.A.S). Division of Nturolog!. the Toronto Hospital and the University of Toronto. Ontario. Canada. Address correspondence and reprint requests to Dr. James A. Sharpe. Division of Neurology. the Toronto Hospital. EC 5-04?. 399 Bathurst Street. Toronto. Ontario. Canada M5T 2S8. preretinal. and \-itreous hemorrhage (Fig. 2). Terson's syndrome was diagnosed. and obsenation was recommended. Three months later. the patient's visual acuity was 20125 OL'. and the hemorrhage resolved. Terson's syndrome refers to the occurrence of \.itreous hemorrhage with tSXH) ( 1 ). Intraocular hemorrhagesubretinal. intraretinal. and preretinal (subhyaloidkcan also occur ( 2 ) . Garfinkle et al. (2) observed vitreous hemorrhage in 3% to 5% of patients with SAH. whereas intraocular hemomhage without vitreous hemorrhage occurred in 20% to m% ( 2 ) . The pathogenesis of Terson's syndrome is unclear. One widely accepted theory (3) suggested that the sudden increase in intracranial pressure in SAH is transmitted to the optic nene sheath through the subarachnoid communication between the ovtic canal and intracranial cavity. The optic nerve sheath dilates and compresses both the central retinal vein and retinochoroidal anastomoses. thus reducing retinal venous drainage. with rupture of retinal vessels and hemorrhage into~the vitreous. Patients with Tenon's syndrome have a poor prognosis. with a mortality rate that is twice that ~f'~atie;ts with SAH in whom there is no vitreous hemorrhage (2 ) . For those who sunive. visual recovery is usually good as the intraocular hemorrhage slowly resolves (4), and conservative management is recommended. Patients should be followed for ocular complications sbch as glaucoma and epiretinal membrane. Nonclearing vitreous hemorrhage may benefit from vitrectomy (5).

Subarachnoid Fluid of the Optic Nerve in Normal Adults

The purpose of the study is to determine the amount of subarachnoid fluid of the optic nerve in normal adults using magnetic resonance (MR) imaging and to investigate whether the subarachnoid fluid is displaced in abduction as assumed by the 30 degree echographic test. The design was a prospective observation study. Twenty-one healthy headache-free adults participated. Ten (48%) were men and 11 (52%) were women with a mean age of 34.3 +/- 7.9 years. Both optic nerves were examined in primary and 45 degrees right and left gazes with T2 fast-spin echo fat-suppressed coronal MR imaging in quadrature head coil. Four MR images, 4 mm apart, starting from 4 mm posterior to the globe were obtained for both nerves simultaneously with an imaging time of 2 minutes and 24 seconds per gaze. Optic nerve and sheath diameters were measured. Mean nerve diameters were 3.2 +/- 0.4 mm anteriorly to 2.6 +/- 0.4 mm posteriorly, and mean sheath diameters were 5.2 +/- 0.9 mm anteriorly to 3.9 +/- 0.4 mm posteriorly. Optic sheath diameters did not change significantly in abduction or adduction. Magnetic resonance imaging can be used effectively to determine the amount of subarachnoid fluid of the optic nerve. In normal adults, the amount of optic nerve subarachnoid fluid is variable and may be substantial. The authors' MR findings show that optic nerve subarachnoid fluid is not displaced significantly with abduction or adduction.

Giant Optic Nerve Cyst Not Associated to Optic Sheath Meningioma

Cystic enlargement of the optic nerve sheath is extremely rare and has been described in the literature in association with optic nerve meningioma. We describe MR findings over a 3.5 year follow-up in a patient with a large slow-growing retrobulbar ONC, not associated with optic nerve sheath meningioma or other optic nerve or orbital disease.

Juxta-dural ring aneurysmの分類と治療法

Surgical treatment of internal carotid artery aneurysms around the carotid siphon is an art that is described elaborately in this paper. The surgical approach to the aneurysms in this region, is as follows: 1) A fronto-temporal approach with the patient in a 45° semi-sitting position to decrease venous pressure. 2) A Dolenc's approach cutting a part of the dura mater of the superior orbital fissure to facilitate removal of the anterior clinoid process and unroofing of the optic canal. 3) Opening of the medial triangle followed by transection of the optic canal dural sheath. Carotid siphon aneurysms can be divided into 3 groups anatomically: aneurysms of the ophthalmic segment (C2), those of the clinoid segment (C3), and those of the horizontal segment (C4). We present 34 cases of aneurysms arising from the C2 or C2/3 segment, 15 cases arising from the C3 or C3/4 segment, and 11 cases arising from the C4 segment. Anatomic localization of the aneurysms was established preoperatively by angiography and three-dimensional CT imaging. Small aneurysms of the ophthalmic segment projecting inferomedially can be clipped using a contralateral approach via the prechiasmatic root.Aneurysms of the ophthalmic segment projecting superiorly can be clipped following resection of the anterior clinoid process. The clinoid process should be resected intradurally with direct visualization of the aneurysms. Straight side-angled clips are suitable for these aneurysms. Carotid cave aneurysms, which include aneurysms of the ophthalmic segment oriented inferomedially and of the clinoid segment projecting postero-medially, can be clipped using curved fenestrated clips via Dolenc's extradural approach. For accurate clipping, opening of the medial triangle and full mobilization of the IC at the clinoid segment and optic nerve by unroofing the optic canal are required.Aneurysms of the horizontal portion are clipped after full exposure of the artery in the cavernous sinus only when the aneurysms are large and symptomatic. We used the fronto-temporal and Dolenc's approaches and applied fenestrated clips to aneurysms oriented postero-medially and straight or oblique clips to aneurysms projecting antero-laterally. Out of 52 aneurysms that underwent surgical clipping, 46 resulted in good post-operative recovery. There were 3 deaths secondary to complications of vasospasm and 3 cases with postoperative visual loss. We highlight the classification of these aneurysms and the surgical techniques we had employed.

MRI findings in children with neurofibromatosis type 1: a prospective study

To determine the frequency and nature of MRI lesions in children with neurofibromatosis type I (NF1), 50 patients aged 8 to 16 years were evaluated prospectively with cranial MRI. Forty-one children were asymptomatic with respect to central nervous system pathology, and 50% were macrocephalic. Sixteen patients (32%) had normal MRI examinations. Thirty-two patients (64%) had high intensity lesions on T2-weighted images and 16 patients (32%) had hyperintense lesions on T1-weighted images. Seven patients (14%) had ventricular dilatation (associated with increased intracranial pressure in 2) and 11 patients (22%) had optic pathway lesions (optic glioma in 7). MRI was superior to CT in differentiating optic sheath thickening and optic nerve tortuosity from optic glioma in four patients. An intracranial tumour (ependymoma) and sphenoid wing dysplasia were evident in individual patients. Findings previously unreported in NF1 included an aqueductal web resulting in hydrocephalus, intraocular neurofibroma resulting in retinal detachment, and asymptomatic enlargement of the septum pellucidum. T1 and T2 signal abnormalities in isolation were not associated with neurological deficits or the occurrence of macrocephaly, and all lesions that required intervention were suspected clinically. Macrocephaly in the absence of increased intracranial pressure or accelerated head growth is not an indication for neuroimaging in children with NF1. However, the majority of children (68%) had disease-specific abnormalities and thus MRI may provide a useful adjunct to clinical evaluation in the diagnosis of equivocal cases.

Lesion discrimination in optic neuritis using high-resolution fat-suppressed fast spin-echo MRI.

Fast spin-echo (FSE) is a new sequence with acquisition times currently down to one-sixteenth of those obtained with conventional spin-echo sequences, which allows high-resolution (512 x 512 matrix) images to be acquired in an acceptable time. We compared the higher resolution of FSE with the medium resolution of a short inversion-time inversion-recovery (STIR) sequence in depicting the optic nerves of healthy controls and patients with optic neuritis. Optic nerve MRI examinations were performed in 18 patients with optic neuritis and 10 normal controls. Two sequences were obtained coronally: fat-suppressed FSE (FSE TR 3250 ms/TEef 68 ms, echo-train length 16, 4 excitations, 24 cm rectangular field of view, 3 mm interleaved contiguous slices, in-plane resolution 0.5 x 0.5 mm) and STIR (TR 2000 ms/TE 50 ms/TI 175 ms, in-plane resolution 0.8 x 0.8 mm, slice thickness 5 mm). FSE demonstrated much more anatomical detail than STIR, e.g. distinction of optic nerve and sheath. Lesions were seen in 20 of 21 symptomatic nerves using FSE and in 18 of 21 using STIR. Nerve swelling or partial cross-sectional lesions of the optic nerve were each seen only on FSE in 3 cases. Fat-suppressed FSE imaging of the optic nerve improves anatomical definition and increases lesion detection in optic neuritis.

The cranial meninges: Anatomic considerations

The anatomy of the cranial dura and leptomeninges is both intricate and complex. A thorough discussion of the protective covering of the brain including the dura, arachnoid, and pia is provided on both gross and microscopic levels. An attempt to include issues of clinical relevance is made, highlighting the Virchow-Robin spaces and the optic sheath. In addition, the normal appearance of the dura and leptomeninges on MRI is presented to establish a framework for the discussion of leptomeningeal pathology.

Aspergillosis of the brain and paranasal sinuses in immunocompromised patients: CT and MR imaging findings.

With the increased survival of patients with severe immunosuppression, it has become more important to recognize the various forms of cerebral and craniofacial aspergillosis. Currently, only small series of patients with this infection have been described; the radiographic diagnosis of cerebral and craniofacial aspergillosis has varied and has been relatively nonspecific. The purpose of our study was to identify neuroimaging patterns in patients with cerebral and craniofacial aspergillosis. Recognition of radiographic patterns of aspergillosis may facilitate earlier radiologic diagnosis and prompt therapy. The imaging and clinical data of eight immunosuppressed patients with cerebral aspergillosis and one patient each with aspergillosis of the orbit, paranasal sinus, and calvaria were evaluated retrospectively. All patients were at risk of developing infection by virtue of poorly controlled diabetes or other types of congenital or acquired immunosuppression (e.g., steroids, chemotherapy). Patients were selected for study if the diagnosis of aspergillosis was established by means of biopsy or autopsy and CT scanning or MR imaging was available for review. CT scans and MR images were compared by two experienced neuroradiologists, who were aware of the diagnosis of aspergillosis, to see if common radiographic patterns could be identified that could be used as predictors of this type of infection. Five patients with cerebral aspergillosis had multiple ring-enhancing lesions consistent with abscesses. Characteristic findings were multiple lesions, an irregular ring of contrast enhancement, and hypointensity of the ring on T2-weighted MR images. Three patients had cortical and subcortical hypodensities on CT scanning or hyperintensities on MR imaging consistent with cerebral cortical and subcortical infarction. Two of these three had superimposed hematoma formation. Three patients had craniofacial aspergillosis. One patient each had enhancing mucosal thickening of the paranasal sinus with secondary intracranial dural enhancement, abnormal enhancement of the optic nerve and sheath with infiltrating enhancing soft tissue within the intraorbital fat, and an enhancing diploetic lesion of the calvaria with underlying dural enhancement. Three different neuroimaging patterns of cerebral aspergillosis were identified in immunosuppressed patients. The first pattern was multiple areas of hypodensity on CT scans or hyperintensity on T2-weighted MR images involving the cortex and/or subcortical white matter consistent with multiple areas of embolic infarction. This pattern could be seen with or without superimposed hemorrhage, identified as hyperdensity on CT scans or as hyperintensity on T1-weighted MR images. The second pattern was multiple intracerebral ring-enhancing lesions consistent with abscesses. The ring was irregular and of low signal on T2-weighted MR images. The third pattern was dural enhancement associated with enhancing lesions in the adjacent paranasal sinus structure or calvaria or dural enhancement of the optic sheath with associated optic nerve and intraorbital fat enhancement. Recognition of these three patterns of aspergillosis in immunosuppressed patients may lead to more effective diagnosis and treatment planning.

Peripapillary Choroidal Neovascular Membrane Associated With an Optic Nerve Coloboma

Optic nerve colobomas are rare congenital anomalies that result from failure of the superior end of the embryonic fissure to close. Ocular abnormalities associated with optic nerve colobomas include the presence of posterior lenticonus, posterior embryotoxon, optic nerve pit, optic sheath cyst, and remnants of the hyaloid artery. 1 We describe a patient with a peripapillary subretinal neovascular membrane associated with an isolated optic nerve coloboma. Report of a Case. —A 48-year-old man who previously had 20/20 OU visual acuity complained of blurred vision in his right eye of 1 month's duration. Best corrected visual acuity was 20/50 OD and 20/20 OS. The anterior segments of both eyes were normal. Ophthalmoscopic examination of the right eye revealed an isolated optic nerve coloboma. The optic nerve was mildly pale, completely excavated, and approximately twice larger than the left in diameter. The retinal vessels entered and exited from the borders and coalesced

Optic Nerve Gliomas and Meningiomas

Optic nerve gliomas are benign astrocytic neoplasms that primarily affect children. The ultimate prognosis for vision is poor. For lesions confined to the optic nerves, long-term survival is excellent, but with involvement of the chiasm and especially of the hypothalamus or third ventricle, prognosis falls significantly. For this group, no form of therapy has proven to be of any benefit. Optic sheath meningiomas are neoplasms arising from arachnoid cap cells. They primarily affect middle-aged adults. Like gliomas, the prognosis for vision is poor, but unlike gliomas, prognosis for life is excellent.

Fenestration of optic nerve sheaths in pseudotumor cerebri

In 15 out of 50 patients with pseudotumor cerebri a fenestration of the retrobulbar optic nerve dural sheath was carried out in order to prevent functional damage due to papilledema. Full and permanent regression of the papilledema resulted in 24 out of 27 eyes without reduction of the elevated CSF pressure. Functionally, the obscurations disappeared on the operated side. Visual acuity and visual fields showed in most cases no change or only a slight improvement. In three eyes with ischemic papilledema the advanced visual loss was even accelerated.Optic nerve sheath fenestration in pseudotumor cerebri seems to be a safe procedure in cases of imminent or beginning visual loss, but not in advanced axonal damage with ischemic signs of papilledema.

Chronic unilateral optic neuropathy: a magnetic resonance study.

We studied the clinical, electrophysiological, and magnetic resonance imaging (MRI) features of 20 patients with chronic unilateral optic neuropathy (CUON): progressive unilateral visual failure lasting a minimum of 6 months. The patients, 10 male and 10 female, ranged in age from 12 to 77 years (mean 44) and had a mean duration of symptoms of 22 months. All had signs of optic nerve dysfunction. Each patient was studied with MRI using a short TI inversion recovery (STIR) sequence to delineate the optic nerve from surrounding orbital tissue. Three distinct groups of patients with CUON were identified using MRI. In the first group (8/20) the optic nerve was compressed by an extrinsic mass, whereas in the second group (5/20) CUON resulted from an intrinsic tumor of the optic nerve or sheath. In both groups STIR sequences compared favorably with computed tomography in identifying mass lesions. MRI was superior in delineating distortion of the optic nerve by mass or tumor extension beyond the orbit. In the third group (7/20) no mass was evident on MRI. However, STIR sequences revealed altered signal (long T1) in clinically symptomatic nerves. In 4 of the patients T2-weighted cerebral MRI disclosed periventricular lesions suggestive of disseminated white matter disease. We conclude that MRI complements clinical and electrophysiological testing in the assessment of CUON.

Pseudotumor Cerebri (Benign Intracranial Hypertension): Etiopathogenesis, Diagnosis, And Management

Pseudotumor Cerebri (Benign Intracranial Hypertension): Etiopathogenesis, Diagnosis, And Management

Optic nerve sheath decompression. Review of 17 cases.

Seventeen patients (19 eyes) with progressive visual loss associated with retrobulbar optic nerve and/or sheath enlargement were treated by surgical nerve sheath decompression at the Bascom Palmer Eye Institute, Miami, from 1969 through 1984. A decision to intervene was based on progressive visual loss unresponsive to other modes of therapy and accompanied by retrobulbar optic nerve sheath enlargement as determined by computed tomography, contrast orbitography, or orbital echography. Follow-up ranged from three months to nine years, with an average of 17 months. Visual function improvement was noted within one month after operation in seven of 19 eyes. The other 12 eyes showed no improvement or continued to worsen. Postoperative complications were infrequent, with motility disturbances being the most common. Optic nerve sheath decompression via the medial orbital approach has a low operative morbidity and may improve visual function in patients with progressive visual loss associated with the accumulation of compressible fluids in the retro-orbital optic nerve sheaths. This relatively safe surgical approach to the retrobulbar optic nerve may also be of future use in the retrieval of optic nerve tissue and fluid for chemical and cytologic analysis.

The development of the human brain and the closure of the rostral neuropore at stage 11.

Twenty embryos of stage 11 (24 days) were studied in detail and graphic reconstructions of twelve of them were prepared. The characteristic feature of this stage is 13-20 pairs of somites. The notochord sensu stricto appears first during this stage, and its rostral and caudal parts differ in origin. Rostrally, the notochordal plate is being transformed into the notochord in a caudorostral direction. The caudal part, however, arises from the axial condensation in the caudal eminence in a rostrocaudal direction. The caudal eminence (or end bud) represents the former primitive streak. The somites are increasing in number at a mean rate of 6.6 h per pair. The rostral neuropore closes towards the end of stage 11. The closure is basically bidirectional, being more rapid in the roof region and producing the embryonic lamina terminalis and future commissural plate in the basal region. The caudal neuropore is constantly open. The brain comprises telencephalon medium (represented by the embryonic lamina terminalis) and a series of neuromeres: 2 for the forebrain (D1 and D2), 1 for the midbrain, and 6-7 for the hindbrain (RhA-C; RhD is not clearly delineated). The forebrain still occupies a small proportion of the total brain, whereas the spinal part of the neural tube is lengthening rapidly. Some occlusion of the lumen of the neural tube was noted in 4 embryos, all of which had an open rostral neuropore. Hence there is at present no evidence that occlusion plays a role in expansion of the human brain. The marginal (primordial plexiform) layer is appearing, particularly in rhombomere D and in the spinal portion of the neural tube. The neural crest is still forming from both the (open) neural groove and the (closed) neural tube, and exclusively from both neural (including optic) and (mainly) otic ectoderm. The optic sulcus is now prominent, and its wall becomes transformed into the optic vesicle towards the end of stage 11. At this time also, an optic sheath derived from mesencephalic crest and optic crest is present. The mitotic figures of the optic neural crest are exceptional in being situated in the external part of the neural epithelium. The otic pit is becoming deeper, and its wall is giving rise to neural crest that is partly added to the faciovestibulocochlear ganglion and partly forms an otic sheath. The nasal plate does not yet give off neural crest.