A direct transcutaneous approach to infraorbital nerve biopsy.

PURPOSE: To describe a novel transcutaneous infraorbital nerve biopsy technique which can be performed to aid in the diagnosis of perineural invasion (PNI) of facial cutaneous squamous cell carcinoma (SCC). METHODS: A single-center retrospective chart review was performed. Patients diagnosed with SCC with PNI via an infraorbital nerve biopsy between February 2019 and February 2020 were included. Data collected consisted of patient demographics, medical history, clinical presentation and exam, histologic and radiographic findings, treatment, and outcomes. RESULTS: Four patients (3 male, 1 female) met inclusion criteria. The mean age at diagnosis was 79.5 years (range 66-85 years). Three of the four patients had a history of facial skin lesions, including actinic keratosis and SCC, involving the nose, cheek, or ear. One patient had no history of cutaneous malignancy. All patients presented with cranial neuropathies, including total V2 hypoesthesia. The most common presenting symptom was facial pain, followed by diplopia, unilateral facial weakness, and hypoesthesia in the V1 and/or V2 distribution. Transcutaneous infraorbital nerve biopsy in all patients revealed squamous cell carcinoma with no biopsy complications. CONCLUSION: Definitive diagnosis of PNI can be challenging but is important to minimize tumor-related morbidity. Infraorbital nerve biopsy can establish this diagnosis, especially in the context of negative or indeterminate imaging findings. This work comprises the first description of a transcutaneous approach to infraorbital nerve biopsy, which is a minimally invasive technique that can be performed in an outpatient procedure suite with limited to no sedation.

Gabapentin and memantine increases randomness of oscillatory waveform in ocular palatal tremor.

Syndrome of oculopalatal tremor (OPT) causes pendular nystagmus of the eyes and its disabling consequence on the visual system. Classic pharmacotherapeutic studies revealed reduction in the eye velocity of the oscillatory waveforms. Subjective improvement in vision, however, remains out of proportionately low. Elegant models depicting quasi-sinusoidal coarse oscillations of the eyes highlighted two distinct oscillators; one at the inferior olive causing primary 2 Hz oscillations, while the second, independent oscillator, at the cerebellum adding the randomness to the waveform. Here we examined whether pharmacotherapy affects the randomness of the oscillatory waveform. Horizontal, vertical, and torsional angular eye positions were measured independently from both eyes as six subjects with OPT directed gaze toward a straight-ahead target. The measurements were performed before administration of alpha-2-delta calcium channel blocker (gabapentin) or NMDA receptor antagonist (memantine) and after the subjects were treated with each of these drugs for at least 8 days. Amplitude and velocity of eye oscillations were reduced by gabapentin and memantine, but there was an increase in the waveform randomness. We found that the increase in randomness was proportionate to the amount of reduction in the waveform velocity or amplitude. Hierarchical clustering revealed distinct patterns of oscillatory waveforms, with each subject belonging to a specific cluster group. The pharmacotherapy changed the waveform clustering pattern of the waveform in each subject. We conclude that in addition to incomplete resolution of the oscillation intensity, increased randomness could be one of the reasons why there is not enough clinical difference in the patients' visual quality.

Incipient Syphilitic Papillitis.

Patients with syphilis can present with optic disc oedema (ODE) without visual compromise, which has been primarily attributed to papilloedema from raised intracranial pressure or optic perineuritis from optic nerve sheath inflammation. We report four cases of ODE in the setting of syphilis with preserved visual function, normal intracranial pressure, and no enhancement of the optic nerve or sheath on magnetic resonance imaging. We propose the term "incipient syphilitic papillitis" for cases presenting with ODE, preserved vision and absence of optic nerve sheath enhancement, which is likely a more common presentation than syphilitic optic perineuritis.

Treatment of Nystagmus.

Acquired and congenital forms of nystagmus are commonly encountered in the course of clinical practice. Although some patients are asymptomatic, many others describe disabling oscillopsia that impairs visual function, social function, and quality of life. Such patients may present to the neurologist to request treatment. Numerous treatment approaches for nystagmus have been proposed, including medical, surgical, and optical treatments. Some of the treatments aim to reduce nystagmus slow-phase speed, whereas others aim to negate the visual consequences of the nystagmus. The approach must be tailored depending on the type of nystagmus, its characteristics, and in some cases, its cause. In this review, the treatment approach for acquired and congenital forms of nystagmus is summarized with an emphasis on treatments that have been evaluated in well-designed clinical trials. Novel approaches that have not yet been evaluated in clinical trials are also discussed.

Third nerve palsy as the initial manifestation of giant cell arteritis.

OBJECTIVE: Giant cell arteritis (GCA) is rarely reported as a cause of third nerve palsy. We describe the presentation and course of patients with third nerve palsy as the sole initial ocular manifestation of GCA. METHODS: Retrospective chart review of patients with third nerve palsy as the presenting sign of GCA. Symptoms, signs, and inflammatory marker levels at presentation and on follow-up were analyzed. All patients had imaging of the brain and circle of Willis, to exclude a compressive or inflammatory lesion, and had a temporal artery biopsy showing granulomatous arteritis. RESULTS: Four patients (aged 63-82) were identified and included. One patient had a complete third nerve palsy with pupil involvement, whereas the other 3 had third nerve palsies without pupil involvement. Three patients had ipsilateral periorbital/brow pain, and the other patient had temporal headache. Two patients reported no systemic symptoms of GCA but had elevated inflammatory markers. One patient had normal inflammatory markers but reported systemic symptoms of GCA. All patients had rapid improvement in symptoms and signs after high-dose oral prednisone was started with all showing complete recovery within weeks. CONCLUSIONS: GCA can rarely present with acute painful third nerve palsy, mimicking the presentation of a microvascular cause. The third nerve palsy often improves rapidly after steroid treatment is started. The presence of GCA symptoms or elevated inflammatory markers in a patient older than 50 years with an acute third nerve palsy should prompt initiation of high-dose steroid treatment and temporal artery biopsy.

Limited Wegener's Granulomatosis Presenting with an Isolated Abduction Deficit.

Wegener's granulomatosis often affects the orbit, typically presenting with painful proptosis. The authors describe a 14 year-old girl, with limited Wegener's granulomatosis, who initially presented with an isolated painless abduction deficit that spontaneously resolved over several weeks. She subsequently developed painful proptosis and diplopia, followed by facial and oral nodules. This case demonstrates that limited Wegener's granulomatosis can rarely present with an isolated painless abduction deficit.

Neuro-ophthalmology of invasive fungal sinusitis: 14 consecutive patients and a review of the literature.

BACKGROUND: Invasive fungal sinusitis is a rare condition that usually occurs in immunocompromised patients and often presents as an orbital apex syndrome. It is frequently misdiagnosed on presentation and is almost always lethal without early treatment. DESIGN: Retrospective case series of 14 consecutive patients with biopsy-proven invasive fungal sinusitis from four tertiary hospitals. PARTICIPANTS: Fourteen patients (10 men and 4 women; age range 46-82 years). METHODS: Retrospective chart review of all patients presenting with invasive fungal sinusitis between 1994 and 2010 at each hospital, with a close analysis of the tempo of the disease to identify any potential window of opportunity for treatment. MAIN OUTCOME MEASURES: Demographic data, background medical history (including predisposing factors), symptoms, signs, radiological findings, histopathological findings, treatment approach and subsequent clinical course were recorded and analysed. RESULTS: Only one patient was correctly diagnosed at presentation. Only two patients were not diabetic or immunocompromised. The tempo was acute in two patients, subacute in nine patients and chronic in three patients. In the subacute and chronic cases, there was about 1 week of opportunity for treatment, from the time there was a complete orbital apex syndrome, and still a chance for saving the patient, to the time there was central nervous system invasion, which was invariably fatal. Only two patients survived - both had orbital exenteration, as well as antifungal drug treatment. CONCLUSIONS: Invasive fungal sinusitis can, rarely, occur in healthy individuals and should be suspected as a possible cause of a progressive orbital apex syndrome.

Retinal Sublayer Analysis in Autoimmune Retinopathy and Identification of New Optical Coherence Tomography Phenotypes.

PURPOSE: Autoimmune retinopathy (AIR) is a poorly characterized disease with a wide phenotypic spectrum, complicating investigations of its underlying pathophysiology. We sought to analyze optical coherence tomography (OCT) retinal thickness changes in AIR patients. METHODS: A retrospective chart review from 2007 to 2017 was performed evaluating AIR patients at a single academic, tertiary referral center. OCT retinal sublayer analysis was performed, and paradoxical thickening phenotypes were reviewed. RESULTS: Twenty-nine AIR patients with positive anti-retinal antibodies and OCT imaging were identified. Overall, AIR patients had thinner retinal sublayers compared to controls; however, 12 patients (41.4%) had paradoxical thickening of the outer plexiform layer (OPL). This revealed two distinct OCT phenotypes. No association was found between retinal sublayer thickness and specific antiretinal antibodies. CONCLUSIONS: While the pathogenicity of antiretinal antibodies remains unclear, the OCT phenotypes observed underscore the potential for identifying clues in the underlying disease processes and clinical diagnosis.

Treatment of ocular myasthenia gravis.

OPINION STATEMENT: Myasthenia gravis (MG) is an autoimmune disorder that is characterized by variable weakness and fatigability. Often, MG presents with only ocular symptoms such as ptosis and diplopia. Treatment of ocular MG is aimed at relieving the symptoms of ptosis and diplopia, as well as preventing the development of generalized MG symptoms. Immune suppression with steroids is often the main therapy. Steroid doses must be increased slowly because of a risk of precipitating myasthenic crisis. After achieving the highest target dose, steroids are then slowly tapered down to the lowest effective dose. Often, acetylcholinesterase inhibitors such as pyridostigmine and neostigmine are also employed to help control symptoms. When steroids are contraindicated, acetylcholinesterase inhibitors can be tried as the primary therapy. Steroid-sparing agents such as azathioprine and mycophenolate may also have a role in treating ocular MG. Other treatments for MG include plasmapheresis, intravenous immunoglobulin, and other immunosuppressive agents, but these are rarely required for ocular MG. Patients should also be evaluated for thymoma. Thymoma should be resected surgically. Ocular MG without thymoma is not usually treated with thymectomy. Topical agents may be useful as additional therapy for mild or moderate ptosis. Nonpharmacologic treatments include occlusive devices, prisms, eyelid supports, contact lenses, and (in long-standing, stable cases) strabismus surgery or eyelid elevation surgery.

Treatment of nystagmus.

OPINION STATEMENT: Patients with congenital and acquired forms of nystagmus are commonly encountered in clinical practice. Many report visual symptoms, such as oscillopsia and blurred vision, which can be alleviated if the nystagmus can be suppressed. Pharmacologic, optical, and surgical treatments are available, with the choice of treatment depending on the characteristics of the nystagmus and the severity of the associated visual symptoms. Downbeat nystagmus can be treated with 4-aminopyridine, 3,4-diaminopyridine, or clonazepam. Upbeat nystagmus can be reduced with memantine, 4-aminopyridine, or baclofen. Torsional nystagmus may respond to gabapentin. Acquired pendular nystagmus in patients with multiple sclerosis is often partially suppressed by gabapentin or memantine. Acquired pendular nystagmus in patients with oculopalatal tremor can respond to gabapentin, memantine, or trihexyphenidyl. Although acquired periodic alternating nystagmus is often completely suppressed by baclofen, memantine can be effective in refractory cases. Seesaw nystagmus can be reduced with alcohol, clonazepam, or memantine. Infantile nystagmus may not cause significant visual symptoms if "foveation periods" are well developed, but the nystagmus can be treated in symptomatic patients with gabapentin, memantine, acetazolamide, topical brinzolamide, contact lenses, or base-out prisms to induce convergence. Several surgical therapies have also been reported to improve infantile nystagmus syndrome (INS), but selection of the appropriate therapy requires preoperative evaluation of visual acuity and nystagmus intensity in different gaze positions. Other treatment options for nystagmus include botulinum toxin injections into the extraocular muscles or retrobulbar space. Electro-optical devices are currently being developed, in order to noninvasively negate the visual consequences of nystagmus.

Miller Fisher syndrome mimicking ocular myasthenia gravis.

PURPOSE.: Miller Fisher syndrome (MFS) is a rare immune-mediated neuropathy that commonly presents with diplopia after the acute onset of complete bilateral external ophthalmoplegia. Ophthalmoplegia is often accompanied by other neurological deficits such as ataxia and areflexia that characterize MFS. Although MFS is a clinical diagnosis, serological confirmation is possible by identifying the anti-GQ1b antibody found in most of the affected patients. We report a patient with MFS who presented with clinical signs suggestive of ocular myasthenia gravis but in whom the correct diagnosis was made on the basis of serological testing for the anti-GQ1b antibody. CASE REPORT.: An 81-year-old white man presented with an acute onset of diplopia after a mild gastrointestinal illness. Clinical examination revealed complete bilateral external ophthalmoplegia and left-sided ptosis. He developed more marked bilateral ptosis, left greater than right, with prolonged attempted upgaze. He was also noted to have a Cogan lid twitch. Same day evaluation by a neuro-ophthalmologist revealed mild left-sided facial and bilateral orbicularis oculi weakness. He had no limb ataxia but exhibited a slightly wide-based gait with difficulty walking heel-to-toe. A provisional diagnosis of ocular myasthenia gravis was made, and anticholinesterase inhibitor therapy was initiated. However, his symptoms did not improve, and serological testing was positive for the anti-GQ1b immunoglobulin G antibody, supporting a diagnosis of MFS. CONCLUSIONS.: Although the predominant ophthalmic feature of MFS is complete bilateral external ophthalmoplegia, it should be recognized that MFS has variable associations with lid and pupillary dysfunction. Such confounding neuro-ophthalmic features require a thorough history, neurological examination, neuroimaging, and serological testing for the anti-GQ1b antibody to arrive at a diagnosis of MFS.

Optic nerve head drusen in black patients.

BACKGROUND: Several studies have suggested racial differences in the prevalence of optic nerve head drusen (ONHD). We aimed to determine the percentage of patients with ONHD who are black and to describe the clinical, ophthalmoscopic, and perimetric findings in these patients. METHODS: We conducted a retrospective chart review of all patients with ONHD seen at our institution between 1989 and 2010. Only black patients with ONHD confirmed on either funduscopy or B-scan ultrasonography were included. Demographic and clinical findings in these patients were recorded and analyzed. RESULTS: Of the 196 patients with confirmed ONHD, 10 (5.1%) were black. This included 7 females and 3 males with ages ranging from 8 to 61 years. Six of the 10 patients had bilateral ONHD. The ONHD were buried in 11 of 16 eyes and exposed in 5 of 16 eyes. Fifteen of 16 eyes with ONHD had small cupless optic nerve heads. Visual fields were normal in 4 of 16 eyes with ONHD. In the remainder, visual field defects included an enlarged blind spot (5 eyes), constricted field (5 eyes), nasal defect (2 eyes), central defect (1 eye), and generalized depression (1 eye). Visual field defects were present in 4 of 5 eyes (80%) with exposed ONHD and 8 of 11 eyes (72.7%) with buried ONHD. None of the patients were related, and none of their examined family members had exposed ONHD on funduscopic examination. CONCLUSIONS: ONHD are rare in blacks, possibly due to the presence of a larger cup-to-disc ratio or a lack of predisposing genetic factors. Visual field defects are common in black patients with both exposed and buried ONHD.

Crossover trial of gabapentin and memantine as treatment for acquired nystagmus.

We conducted a masked, crossover, therapeutic trial of gabapentin (1,200mg/day) versus memantine (40 mg/day) for acquired nystagmus in 10 patients (aged 28-61 years; 7 female; 3 multiple sclerosis [MS]; 6 post-stroke; 1 post-traumatic). Nystagmus was pendular in 6 patients (4 oculopalatal tremor; 2 MS) and jerk upbeat, hemi-seesaw, torsional, or upbeat-diagonal in each of the others. For the group, both drugs reduced median eye speed (p < 0.001), gabapentin by 32.8% and memantine by 27.8%, and improved visual acuity (p < 0.05). Each patient improved with 1 or both drugs. Side effects included unsteadiness with gabapentin and lethargy with memantine. Both drugs should be considered as treatment for acquired forms of nystagmus.

Eye movements in amyotrophic lateral sclerosis and its mimics: a review with illustrative cases.

Abnormal eye movements are increasingly recognised in patients with amyotrophic lateral sclerosis (ALS) and, when they occur, may provide insights into the pattern and pathogenesis of the disease process. In patients with disorders that mimic ALS, abnormal eye movements may point to the correct diagnosis. In both of these circumstances, systematic examination of eye movements and interpretation of the findings with reference to modern concepts of their neural substrate will aid diagnosis and suggest pathogenesis. Here, key points with illustrative case histories and eye movement records are highlighted.

The Berlin questionnaire screens for obstructive sleep apnea in idiopathic intracranial hypertension.

BACKGROUND: Obstructive sleep apnea (OSA) may be associated with idiopathic intracranial hypertension (IIH), a disorder most commonly occurring in young obese women. Because polysomnography, the standard test for diagnosing OSA, is expensive and time consuming, questionnaires have been developed to identify persons with OSA. The Berlin questionnaire (BQ) reliably identifies middle-aged and older persons in the community who are at high-risk for OSA. We aimed to validate the BQ as a screening tool for OSA in IIH patients. METHODS: Patients with newly diagnosed IIH completed the BQ and then underwent diagnostic polysomnography. The BQ was scored as high or low risk for OSA, and the diagnosis of OSA was based on polysomnography findings. OSA was defined as an apnea-hypopnea index of ≥ 5 on polysomnography. RESULTS: Thirty patients were evaluated (24 women; 15 white and 15 black; age, 16-54 years [median, 32 years]; body mass index, 27.3-51.7 kg/m2 [median, 39.8 kg/m2]). Twenty patients (66.7%) had a high-risk BQ score and 18 (60%) exhibited OSA. Fifteen of 20 (75%) with a high-risk BQ score had OSA, while 3 of 10 (30%) with a low-risk score had OSA (Fisher test, P = 0.045). The sensitivity and specificity of the BQ for OSA in IIH patients were 83% and 58%, respectively, whereas the positive predictive value was 75%. CONCLUSION: A low-risk BQ score identifies IIH patients who are unlikely to have OSA. Polysomnography should be considered in those with a high-risk score.

Update in the Management of Idiopathic Intracranial Hypertension.

Idiopathic intracranial hypertension is a syndrome of increased intracranial pressure of unknown cause that most often occurs in women of childbearing age. Most patients are overweight or obese with a history of recent weight gain. Following a brief review of the symptoms and signs, we discuss the approach to assessment and monitoring of this condition. We then present a practical approach to treatment. Because patients frequently struggle with weight loss and can also have refractory headaches and coexisting psychosocial issues, we emphasize the importance of a multidisciplinary approach to the management of this common condition.

Muscimol inactivation caudal to the interstitial nucleus of Cajal induces hemi-seesaw nystagmus.

Hemi-seesaw nystagmus (hemi-SSN) is a jerk-waveform nystagmus with conjugate torsional and disjunctive vertical components. Halmagyi et al. in Brain 117(Pt 4):789-803 (1994), reported hemi-SSN in patients with unilateral lesions in the vicinity of the Interstitial Nucleus of Cajal (INC) and suggested that an imbalance in projections from the vestibular nuclei to the INC was the source of the nystagmus. However, this hypothesis was called into question by Helmchen et al. in Exp Brain Res 119(4):436-452 (1998), who inactivated INC in monkeys with muscimol (a GABA(A) agonist) and induced failure of vertical gaze-holding (neural integrator) function but not hemi-SSN. We injected 0.1-0.2 microl of 2% muscimol into the supraoculomotor area, 1-2 mm dorso-lateral to the right oculomotor nucleus and caudal to the right INC. A total of seven injections in two juvenile rhesus monkeys were performed. Hemi-SSN was noted within 5-10 min after injection for six of the injections. Around the time the hemi-SSN began, a small skew deviation also developed. However, there was no limitation of horizontal or vertical eye movements, suggesting that the nearby oculomotor nucleus was not initially compromised. Limitations in eye movement range developed about (1/2)-1 h following the injections. Clinical signs that were observed after the animal was released to his cage included a moderate to marked head tilt toward the left (contralesional) side, consistent with an ocular tilt reaction. We conclude that hemi-SSN can be caused by lesions just caudal to the INC, whereas lesions of the INC itself cause down-beat nystagmus and vertical gaze-holding failure, as demonstrated by Helmchen et al. Combined deficits may be encountered with lesions that involve several midbrain structures.

Therapy for nystagmus.

Pathological forms of nystagmus and their visual consequences can be treated using pharmacological, optical, and surgical approaches. Acquired periodic alternating nystagmus improves following treatment with baclofen, and downbeat nystagmus may improve following treatment with aminopyridines. Gabapentin and memantine are helpful in reducing acquired pendular nystagmus due to multiple sclerosis. Ocular oscillations in oculopalatal tremor may also improve following treatment with memantine or gabapentin. The infantile nystagmus syndrome (INS) may have only a minor impact on vision if "foveation periods" are well developed, but symptomatic patients may benefit from treatment with gabapentin, memantine, or base-out prisms to induce convergence. Several surgical therapies are also reported to improve INS, but selection of the optimal treatment depends on careful evaluation of visual acuity and nystagmus intensity in various gaze positions. Electro-optical devices are a promising and novel approach for treating the visual consequences of acquired forms of nystagmus.