Idiopathic Intracranial Hypertension is Associated with a Higher Burden of Visible Cerebral Perivascular Spaces: The Glymphatic Connection.

BACKGROUND AND PURPOSE: Research suggests a connection between idiopathic intracranial hypertension and the cerebral glymphatic system. We hypothesized that visible dilated perivascular spaces, possible glymphatic pathways, would be more prevalent in patients with idiopathic intracranial hypertension. This prevalence could provide a biomarker and add evidence to the glymphatic connection in the pathogenesis of idiopathic intracranial hypertension. MATERIALS AND METHODS: We evaluated 36 adult (older than 21 years of age) patients with idiopathic intracranial hypertension and 19 controls, 21-69 years of age, who underwent a standardized MR imaging protocol that included high-resolution precontrast T2- and T1-weighted images. All patients had complete neuro-ophthalmic examinations for papilledema. The number of visible perivascular spaces was evaluated using a comprehensive 4-point qualitative rating scale, which graded the number of visible perivascular spaces in the centrum semiovale and basal ganglia; a 2-point scale was used for the midbrain. Readers were blinded to patient diagnoses. Continuous variables were compared using a Student t test. RESULTS: The mean number of visible perivascular spaces overall was greater in the idiopathic intracranial hypertension group than in controls (4.5 [SD, 1.9] versus 2.9 [SD, 1.9], respectively; P = .004). This finding was significant for centrum semiovale idiopathic intracranial hypertension (2.3 [SD, 1.4] versus controls, 1.3 [SD, 1.1], P = .003) and basal ganglia idiopathic intracranial hypertension (1.7 [SD, 0.6] versus controls, 1.2 [SD, 0.7], P = .009). There was no significant difference in midbrain idiopathic intracranial hypertension (0.5 [SD, 0.5] versus controls, 0.4 [SD, 0.5], P = .47). CONCLUSIONS: Idiopathic intracranial hypertension is associated with an increased number of visible intracranial perivascular spaces. This finding provides insight into the pathophysiology of idiopathic intracranial hypertension, suggesting a possible relationship between idiopathic intracranial hypertension and glymphatic dysfunction and providing another useful biomarker for the disease.

Neuro-ophthalmic side effects of molecularly targeted cancer drugs.

The past two decades has been an amazing time in the advancement of cancer treatment. Molecularly targeted therapy is a concept in which specific cellular molecules (overexpressed, mutationally activated, or selectively expressed proteins) are manipulated in an advantageous manner to decrease the transformation, proliferation, and/or survival of cancer cells. In addition, increased knowledge of the role of the immune system in carcinogenesis has led to the development of immune checkpoint inhibitors to restore and enhance cellular-mediated antitumor immunity. The United States Food and Drug Administration approval of the chimeric monoclonal antibody (mAb) rituximab in 1997 for the treatment of B cell non-Hodgkin lymphoma ushered in a new era of targeted therapy for cancer. A year later, trastuzumab, a humanized mAb, was approved for patients with breast cancer. In 2001, imatinib was the first small-molecule kinase inhibitor approved. The approval of ipilimumab-the first in class immune checkpoint inhibitor-in 2011 serves as a landmark period of time in the resurgence of immunotherapy for cancer. Despite the notion that increased tumor specificity results in decreased complications, toxicity remains a major hurdle in the development and implementation of many of the targeted anticancer drugs. This article will provide an overview of the current cellular and immunological understanding of cancer pathogenesis-the foundation upon which molecularly targeted therapies were developed-and a description of the ocular and neuro-ophthalmic toxicity profile of mAbs, immune checkpoint inhibitors, and small-molecule kinase inhibitors.

Stereotactic radiotherapy for malignancies involving the trigeminal and facial nerves.

Involvement of a cranial nerve caries a poor prognosis for many malignancies. Recurrent or residual disease in the trigeminal or facial nerve after primary therapy poses a challenge due to the location of the nerve in the skull base, the proximity to the brain, brainstem, cavernous sinus, and optic apparatus and the resulting complex geometry. Surgical resection caries a high risk of morbidity and is often not an option for these patients. Stereotactic radiosurgery and radiotherapy are potential treatment options for patients with cancer involving the trigeminal or facial nerve. These techniques can deliver high doses of radiation to complex volumes while sparing adjacent critical structures. In the current study, seven cases of cancer involving the trigeminal or facial nerve are presented. These patients had unresectable recurrent or residual disease after definitive local therapy. Each patient was treated with stereotactic radiation therapy using a linear accelerator based system. A multidisciplinary approach including neuroradiology and surgical oncology was used to delineate target volumes. Treatment was well tolerated with no acute grade 3 or higher toxicity. One patient who was reirradiated experienced cerebral radionecrosis with mild symptoms. Four of the seven patients treated had no evidence of disease after a median follow up of 12 months (range 2-24 months). A dosimetric analysis was performed to compare intensity modulated fractionated stereotactic radiation therapy (IM-FSRT) to a 3D conformal technique. The dose to 90% (D90) of the brainstem was lower with the IM-FSRT plan by a mean of 13.5 Gy. The D95 to the ipsilateral optic nerve was also reduced with IM-FSRT by 12.2 Gy and the D95 for the optic chiasm was lower with FSRT by 16.3 Gy. Treatment of malignancies involving a cranial nerve requires a multidisciplinary approach. Use of an IM-FSRT technique with a micro-multileaf collimator resulted in a lower dose to the brainstem, optic nerves and chiasm for each case examined.

Retinal fibrovascular proliferation associated with Nocardia subretinal abscess.

PURPOSE: To report the development of extensive fibrovascular proliferation in association with Nocardia subretinal abscess. METHOD: Case report. RESULTS: Extensive retinal neovascularization with tractional retinal detachment developed soon after ocular involvement in a 61-year-old patient with systemic nocardiosis. Fundus fluorescein angiography showed extensive area of capillary nonperfusion and severe leakage from the neovascular complex. The Nocardia subretinal abscess responded to systemic antibiotics, and the retinal neovascularization and tractional retinal detachment stabilized after 3 months. CONCLUSIONS: Retinal ischemia and severe retinal neovascularization may complicate intraocular nocardiosis. The authors propose secondary retinal vasculitis as a contributing factor towards the development of retinal ischemia in this setting.

Orbital complications of functional endoscopic sinus surgery: MR and CT findings.

AIM: To describe the radiological findings of ophthalmic complications during functional endoscopic sinus surgery (FESS) and correlate them with the clinical manifestations and mechanisms of injury. METHODS: This was a retrospective review of the clinical and cross-sectional imaging findings of 9 patients with orbital complications during FESS. RESULTS: The most common site of entry into the orbit during FESS was the lower medial orbital wall (7 of 9), followed by the inferior orbital wall, resulting in injury to the medial rectus (4 of 9) and, less frequently, the inferior rectus (2 of 9) or superior oblique muscles (1 of 9). Extensive scarring on imaging (3 of 9) was associated with global ocular motility dysfunction. In contrast, localized scarring (3 of 9) or extraocular muscle trauma (6 of 9) resulted in disturbance of eye movement in the direction of gaze from the injured site. CONCLUSIONS: Orbital magnetic resonance and computed tomography findings correlate very well with the abnormal eye movements clinically observed, and can assist in clarifying the cause of injury and guide surgical corrective management of patients suffering orbital complications from FESS. Radiologists should be familiar with the recent developments in FESS instrumentation as well as with the most commonly injured structures within the orbit.

Giant cell arteritis: diagnosis and management.

Visual loss caused by giant cell arteritis is a medical emergency that requires prompt recognition and treatment with systemic corticosteroids. A delay in diagnosis can lead to devastating ophthalmic and systemic complications. Recent advances in genetic and immunocytochemical research techniques have led to greater understanding of the underlying pathomechanisms of giant cell arteritis. Giant cell arteritis is a systemic condition with a strong predilection for the ocular vasculature. Visual symptoms are often the presenting manifestation of the disease, placing the ophthalmologist in a critical position for early diagnosis and treatment. Maintenance of a high clinical suspicion in the appropriate clinical setting is important in establishing an early diagnosis. Because of the complex nature of the disease process, many cases may be a therapeutic challenge requiring prolonged immunosuppression.

Septo-optic dysplasia with olfactory tract and bulb hypoplasia.

Optic nerve hypoplasia can be associated with other central nervous system malformations. When associated with absence of the septum pellucidum or thinning of the corpus callosum, it is termed septo-optic dysplasia. Considered to be a first trimester event, the embryologic timing and etiology of this syndrome still is not clearly defined. This report represents the first documented case of septo-optic dysplasia with associated hypoplasia of the olfactory tract. Optic nerve hypoplasia is attributed to an abnormal developmental process during gestation. Generally accepted to be due to a first trimester insult, the timing of this abnormality has been debated given its association with other central nervous system abnormalities. These central nervous system abnormalities often include cerebral hemispheric and hypothalmic-pituitary axis abnormalities. Specifically, the presence of optic nerve hypoplasia with absence of the septum pellucidum and thinning of the corpus callosum has been termed septo-optic dysplasia or de Morsier's syndrome. Septo-optic dysplasia in association with olfactory tract and bulb hypoplasia has not been reported previously.

Ocular motility complications after endoscopic sinus surgery with powered cutting instruments.

OBJECTIVE: The purpose of this study was to describe 2 unique cases of ocular motility dysfunction after powered endoscopic sinus surgery and identify potential risk factors for extraocular muscle injury. STUDY DESIGN: Interventional case series. RESULTS: Patient 1 developed a restrictive global ophthalmoplegia after inadvertent entry into the medial orbit during powered endoscopic sinus surgery. Patient 2 had complete loss of adduction of the left eye as a result of transection of the medial rectus muscle by a powered cutting instrument. CONCLUSIONS: Despite advances in endoscopic sinus surgery technique and instrumentation, serious ophthalmic complications may still occur. Inadvertent entry into the medial orbital wall can result in ocular motility complications. Furthermore, it is possible that attraction of orbital contents into the tip of a powered cutting instrument may occur without significant entry into the orbital cavity. SIGNIFICANCE: It is important for endoscopic sinus surgeons to be aware of the intimate anatomical relationship between the orbit and sinuses, as well as the potential risks of the current instruments used in endoscopic sinus surgery.

Superficial temporal artery biopsy diagnostic for lung carcinoma.

PURPOSE: To report a unique finding of metastatic tumor cells in the lumen of a superficial temporal artery biopsy specimen in a patient with severe visual loss and optic neuropathy. METHODS: Case report. RESULTS: A 69-year-old man presented with anorexia, pancranial headaches, and acute unilateral visual loss. Ophthalmic examination showed a visual acuity of no light perception and an amaurotic pupil in the left eye. Fundus examination was normal. A superficial temporal artery biopsy, performed for presumed arteritic posterior ischemic optic neuropathy, demonstrated intraluminal cells with irregular nuclei and prominent nucleoli suggestive of metastatic malignancy. Further systemic evaluation uncovered a poorly differentiated adenocarcinoma of the lung with intravascular infiltration and multiple distant metastases. CONCLUSION: Extensive systemic intravascular tumor embolization may be associated with optic neuropathy.

Facial nerve injury following superficial temporal artery biopsy.

BACKGROUND: With proper training, superficial temporal artery biopsy is a safe office procedure with few complications. Surgeons from different disciplines, including ophthalmologists, dermatologists, general surgeons, and plastic surgeons may be called upon to perform this common procedure to confirm giant cell arteritis. OBJECTIVE: To emphasize the surgical anatomy of the scalp as it pertains to superficial temporal artery biopsy and to raise awareness that significant complications can occur after superficial temporal artery biopsy. METHOD: Case report. RESULTS: A 75-year-old woman with presumed giant cell arteritis developed frontalis muscle paralysis following a superficial temporal artery biopsy. Biopsy selection site within the danger zone combined with deep dissection carries the greatest risk of injury to the temporal branches of the facial nerve. CONCLUSION: Any surgeon involved in the practice of performing superficial temporal artery biopsies should have a thorough understanding of proper surgical techniques and regional anatomy to avoid potential devastating complications.

Tensilon and the diagnosis of myasthenia gravis: are we using the Tensilon test too much?

BACKGROUND: Tensilon (edrophonium chloride) is a reversible acetylcholinesterase inhibitor used in the diagnosis of myasthenia gravis, diagnosis and treatment of arrhythmias, detection of early digitalis toxicity, reversal of neuromuscular blockade, and other medical conditions. Toxicity associated with Tensilon use has appeared in the literature for decades. REVIEW SUMMARY: This review discusses the risks of Tensilon and the information practitioners should know before administering the drug. We review the literature regarding serious toxicity of this drug and offer recommendations for its safe use. CONCLUSIONS: A careful medication history should be taken before the administration of Tensilon. Additionally, physicians should be aware of appropriate alternative methods of diagnosis before choosing to administer Tensilon. Physicians should be aware of the clinical situations where the Tensilon test no longer is indicated.

MR characteristics of muslin-induced optic neuropathy: report of two cases and review of the literature.

Muslin-induced optic neuropathy is a rarely reported but important cause of delayed visual loss after repair of intracranial aneurysms. Most of the previously reported cases were published before the introduction of MR imaging. We describe the clinical features and MR appearance of two cases of delayed visual loss due to "muslinoma," and compare them with the 21 cases reported in the literature.