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Biomedical subjects

Nicholas J Volpe

Publications and source records attributed to Nicholas J Volpe.

15 recordsLinked to original sources

Relation of visual function to retinal nerve fiber layer thickness in multiple sclerosis.

PURPOSE: To examine the relation of visual function to retinal nerve fiber layer (RNFL) thickness as a structural biomarker for axonal loss in multiple sclerosis (MS), and to compare RNFL thickness among MS eyes with a history of acute optic neuritis (MS ON eyes), MS eyes without an optic neuritis history (MS non-ON eyes), and disease-free control eyes. DESIGN: Cross-sectional study. PARTICIPANTS: Patients with MS (n = 90; 180 eyes) and disease-free controls (n = 36; 72 eyes). METHODS: Retinal never fiber layer thickness was measured using optical coherence tomography (OCT; fast RNFL thickness software protocol). Vision testing was performed for each eye and binocularly before OCT scanning using measures previously shown to capture dysfunction in MS patients: (1) low-contrast letter acuity (Sloan charts, 2.5% and 1.25% contrast levels at 2 m) and (2) contrast sensitivity (Pelli-Robson chart at 1 m). Visual acuity (retroilluminated Early Treatment Diabetic Retinopathy charts at 3.2 m) was also measured, and protocol refractions were performed. MAIN OUTCOME MEASURES: Retinal nerve fiber layer thickness measured by OCT, and visual function test results. RESULTS: Although median Snellen acuity equivalents were better than 20/20 in both groups, RNFL thickness was reduced significantly among eyes of MS patients (92 mum) versus controls (105 mum) (P<0.001) and particularly was reduced in MS ON eyes (85 mum; P<0.001; accounting for age and adjusting for within-patient intereye correlations). Lower visual function scores were associated with reduced average overall RNFL thickness in MS eyes; for every 1-line decrease in low-contrast letter acuity or contrast sensitivity score, the mean RNFL thickness decreased by 4 mum. CONCLUSIONS: Scores for low-contrast letter acuity and contrast sensitivity correlate well with RNFL thickness as a structural biomarker, supporting validity for these visual function tests as secondary clinical outcome measures for MS trials. These results also suggest a role for ocular imaging techniques such as OCT in trials that examine neuroprotective and other disease-modifying therapies. Although eyes with a history of acute optic neuritis demonstrate the greatest reductions in RNFL thickness, MS non-ON eyes have less RNFL thickness than controls, suggesting the occurrence of chronic axonal loss separate from acute attacks in MS patients.

Acute Disease↗

Intermittent headaches as the presenting sign of subacute angle-closure glaucoma.

Subacute angle closure causes intermittent episodes of transiently elevated intraocular pressure. Headache is often the chief complaint, which may lead to misdiagnosis. The authors examined headache characteristics and consequences of delayed diagnosis. Patients presenting with headaches have a substantial delay in diagnosis, contributing to permanent ocular damage and glaucoma. Patients with subacute angle closure misdiagnosed with migraine are older and have shorter-duration headaches than patients with typical migraine.

Age Factors↗

Factors influencing reaction time during automated kinetic perimetry on the Tübingen computer campimeter.

PURPOSE: To determine the effect of age, examination, location, luminance, subject, and vigilance on reaction time (RT) in automated kinetic perimetry. METHODS: Thirty-six normal volunteers (20-70 years old) underwent kinetic campimetric examinations, during which RTs (time from appearance of a stimulus to response) were recorded. Stimuli with a diameter of 26 minutes of arc (Goldmann III) were presented on horizontal vectors with an angular velocity of 2 deg/s. Thirty-two positions in the 30 degrees radius visual field were tested six times, at luminance levels of 41.62 and 110 cd/m2 (background 10 cd/m2). An analysis of RT variance (ANCOVA) was performed. RESULTS: Median RT increased with age from 370 ms (20-30-year-old subjects) to 440 ms (60-70-year-old subjects). There was a strong dependency of RT from the individual subjects examined (means range, 313-411 ms), from the course of one examination period, from the examination and stimulus luminance, and from the location in the visual field. CONCLUSIONS: Reaction time during automated kinetic perimetry varies considerably. This study shows that the factors of age, the subject examined, his or her daily condition, the course within one examination period, and the stimulus location and luminance are of relevance. For a much more reliable prediction of individual RTs and thus a precise assessment of local kinetic thresholds, application of some additional kinetic stimuli (RT time vectors) within the intact visual field areas is necessary.

Adult↗

Acute ocular motor mononeuropathies: prospective study of the roles of neuroimaging and clinical assessment.

The role for immediate neuroimaging in patients 50 years of age or older with acute isolated third, fourth, and sixth nerve palsies is controversial. We prospectively evaluated 66 patients, aged 50 years and older (median 67 years, range 50-85), with acute isolated ocular motor mononeuropathies. Our purpose was to evaluate both the role of neuroimaging and the role of clinical assessment in determining etiology. We found that clinical features, including time to maximal diplopic symptoms, were not predictive of etiology (median 2 days to maximal diplopic symptoms for both peripheral microvascular and other etiologies). The presence of any common vascular risk factor, including diabetes mellitus, hypertension, hypercholesterolemia, or coronary artery disease, was significantly associated with peripheral microvascular etiology in this cohort (p=0.0004, Fisher's exact test). Despite the high prevalence of peripheral microvascular ischemia as an etiology in this age group, other causes were identified by magnetic resonance imaging (MRI) or computed tomography (CT) scanning in 14% of patients. Diagnoses included brainstem and skull base neoplasms, brainstem infarcts, aneurysms, demyelinating disease, and pituitary apoplexy. Neuroimaging procedures may have a role in the initial evaluation of patients 50 years of age or older with acute ocular motor mononeuropathies.

Abducens Nerve Diseases↗

Computerized kinetic perimetry detects tubular visual fields in patients with functional visual loss.

PURPOSE: To report a novel test that uses computerized kinetic perimetry to detect tubular visual fields in patients with functional visual loss. DESIGN: Observational case series. METHODS: Ten patients who demonstrated generalized visual field constriction on prior examinations underwent testing combining computerized kinetic perimetry with a reversed Galilean telescope, used for optical visual field expansion. RESULTS: Six patients with physiologic visual field constriction demonstrated expansion of their visual fields with the use of the reversed telescope. Four patients with functional visual loss responded to the reversed telescope by demonstrating tubular visual fields, with responses equal to or smaller than their demonstrated visual fields delineated without the telescope. CONCLUSIONS: This test uses a computerized kinetic examination to reduce the subjective nature of tangent screen testing for tubular visual fields and to provide a computerized recording of visual fields. This method is a novel and easy-to-use technique to demonstrate functional visual loss.

Computing Methodologies↗

Rapid cognitive decline following lumbar puncture in a patient with a dural arteriovenous fistula.

BACKGROUND: Dural arteriovenous fistulas (DAVFs) are frequently accompanied with raised intracranial pressure and clinical findings suggestive of pseudotumor cerebri. However, unlike pseudotumor cerebri, the clinical response to lumbar cerebrospinal fluid (CSF) removal can vary from beneficial to acute clinical deterioration leading to death. The criteria for the safe use of lumbar puncture (LP) in patients with a DAVF are not well established. METHODS: A 61-year-old man presented with visual difficulty. Magnetic resonance imaging (MRI) and angiography revealed a left transverse sinus DAVF. He underwent multiple embolizations of arterial feeders over 3 years. He was then noted to have cognitive deficits in short term memory, listening, and concentrating. Over several days after an LP he became increasingly lethargic but arousable. Within hours after a repeat LP there was a rapid deterioration in the patient's level of consciousness and he became unarousable. RESULTS: A brain MRI revealed extensive dilated cortical veins and left temporal lobe venous ischemia without tonsillar herniation. A cerebral angiogram showed an extensive left transverse sinus DAVF with an occluded lateral transverse sinus and increased retrograde venous drainage. Embolization of the arterial feeders in combination with trans-venous coil embolization of the left transverse sinus reversed the patient's neurologic decline. He was discharged neurologically intact except for his chronic visual acuity problems. CONCLUSION: We speculate that when a DAVF manifests retrograde venous flow sufficient to cause cognitive deficits, lumbar CSF drainage must be undertaken with extreme caution.

Central Nervous System Vascular Malformations↗

Cavernous sinus fistulas: carotid cavernous fistulas and dural arteriovenous malformations.

Direct and indirect carotid cavernous sinus fistulas are uncommon vascular anomalies that result in increased pressure in the cavernous sinus. The subsequent changes in blood flow lead to orbital venous congestion, cranial neuropathies, and glaucoma. The following review summarizes knowledge of the clinical features, natural history, diagnostic testing, and therapy for carotid cavernous sinus fistulas.

Angioplasty↗

Bilateral optic nerve infiltration in central nervous system leukemia.

PURPOSE: To report the case of a 58-year-old man with sequential bilateral retrolaminar leukemic infiltration of the optic nerves who presented with normal-appearing optic nerves and no optic nerve enhancement. DESIGN: Interventional case report. METHODS: A 58-year-old man with chronic myelogenous leukemia (CML) developed progressive vision loss to no light perception in both eyes over four days. The patient received 14 doses of external beam irradiation and 10 cycles of intrathecal cytarabine. Despite treatment, he developed optic nerve pallor, and visual acuity remained no light perception in both eyes. CONCLUSIONS: In a patient with leukemia, leukemic optic nerve infiltration may occur even with normal-appearing optic nerves and a normal magnetic resonance image. It is important to maintain a high clinical suspicion for optic nerve infiltration so that prompt local irradiation may be initiated.

Antimetabolites, Antineoplastic↗

The role of unilateral temporal artery biopsy.

PURPOSE: To examine the role of unilateral temporal artery biopsy (TAB) in suspected giant cell arteritis (GCA). DESIGN: Retrospective interventional case series. PARTICIPANTS: We identified 181 subjects from pathology and diagnostic code databases at the University of Pennsylvania Medical Center who underwent TAB between January 1990 and January 2001. METHODS: The medical records for all subjects who underwent TAB were reviewed. Follow-up information was obtained by telephone or record review for those patients who had negative unilateral TAB. MAIN OUTCOME MEASURES: Follow-up information for patients with unilateral negative TAB was reviewed for potential adverse outcomes caused by missed or delayed diagnoses of GCA. Presenting signs and symptoms and laboratory values were recorded for all subjects. Comparisons of clinical profiles between subsets of subjects were performed using Fisher's exact test, significance level alpha = 0.01. RESULTS: Follow-up information was available for 88 (86%) of 102 subjects who had unilateral negative biopsy samples. One (1%) subjects of 88 had a subsequent positive contralateral TAB; no adverse outcomes occurred for this subject or for any other subjects with unilateral negative TAB. Compared with subjects who had unilateral positive or who underwent bilateral TAB (n = 74), those who had unilateral negative TAB (n = 88) had a significantly lower prevalence of jaw claudication (P = 0.007). Compared with subjects diagnosed with GCA (n = 39), those with unilateral negative TAB (n = 88) had significantly lower frequencies of jaw claudication (P = 0.001), "chalky white" optic disc edema (P = 0.002), and fever (P < 0.0001). Compared with subjects with positive TAB (n = 33), subjects with negative TAB (n = 148) had significantly lower prevalence of jaw claudication (P < 0.0001), "chalky white" disc edema (P = 0.0002), pale disc edema (P = 0.006), or any systemic symptom other than headache (P = 0.0002). ("Chalky white" denotes notably extreme disc pallor). The most common indications for biopsy in subjects with unilateral negative TAB were elevated erythrocyte sedimentation rate (ESR) (74%), headache (69%), visual complaints (58%), and ophthalmic signs (52%). Although ESR was a significant predictor of positive TAB overall (unilateral and bilateral TAB) in logistic regression models accounting simultaneously for subject age (P = 0.04), ESR did not significantly predict unilateral negative status in our patients (P = 0.13). CONCLUSIONS: In this cohort of patients, unilateral TAB was associated with an extremely low frequency (1%) of subsequent positive contralateral TAB and was not associated with adverse visual or neurologic outcomes for any subject. We conclude that in the hands of experienced physicians, a unilateral TAB is sufficient to exclude a diagnosis of GCA in populations for which clinical suspicion is low. Jaw claudication, pale optic disc edema, particularly "chalky white" disc edema, fever, or any systemic symptom other than headache should raise suspicion for a diagnosis of GCA.

Biopsy↗

Laser pointer visual field screening.

BACKGROUND: Sensitivity of confrontation visual field (CVF) screening is low unless defects are significant. We compared the sensitivity of laser pointer visual field screening (LVF) with conventional CVF for identifying eyes with abnormal automated perimetry. METHODS: Ninety consecutive patients presenting for HVF prospectively underwent a masked comparison of CVF and LVF testing (175 eyes) from April to May 2000. LVF was performed using a laser pointer target projected onto a tangent screen. Points were tested in random fashion on either side of the vertical and horizontal meridians, near central fixation, around the blind spot, and in each quadrant. Single and double simultaneous finger counting was used to test CVF. RESULTS: LVF demonstrated significantly greater sensitivity as compared with CVF (73% versus 31%, P = 0.001) in identifying field defects found on HVF. Specificities for LVF and CVF were 82% and 99%, respectively. The average testing times per eye were 0.5 minute for CVF, 1.5 minutes for LVF, and 8.0 minutes for HVF. CONCLUSIONS: In this cohort, laser visual field testing was significantly more sensitive than confrontation testing. It may represent an effective, time-efficient tool for visual field screening.

Cohort Studies↗

Spinocerebellar ataxia type 7 (SCA7) shows a cone-rod dystrophy phenotype.

Autosomal dominant spinocerebellar ataxia 7 is associated with retinal degeneration. SCA7, the causative gene, encodes ataxin-7, a ubiquitous 892 amino acid protein of variable sub-cellular localization, and the disease is due to expansion of an unstable CAG repeat in the coding region of the gene. Recent increases in understanding of the mechanisms ofSCA7 -related retinopathy from in vitro and murine model studies prompted us to perform a detailed study of the retinal phenotype of affected members of a family with SCA7 mutation (45-47 CAG repeats). There was a spectrum of severity from mild to severe dysfunction. Early functional abnormalities were at both photoreceptor and post-receptoral levels. When cone and rod photoreceptor dysfunction was present, it was approximately equal. Regional retinal dysfunction was evident: there was more dysfunction centrally than peripherally with least effect in the midperiphery. In vivo cross-sectional retinal images with optical coherence tomography showed an early disease stage of altered foveal lamination (abnormal area of low reflectivity splitting the outer retina-choroidal complex) accompanied in the parafovea by reduced retinal thickness. Later disease stages showed foveal and parafoveal retinal thinning. The phenotype in this family with SCA7 is that of a cone-rod dystrophy. These observations increase interest in a recent hypothesis that ataxin-7 may interfere with the function of CRX (cone-rod homeobox), a transcription factor regulating photoreceptor genes and a cause of a cone-rod dystrophy phenotype in man.

Adult↗

Prolonged premonitory optic disc signs in anterior ischemic optic neuropathy.

A patient displayed a pink mass on the right optic disc and normal visual function that was diagnosed as a capillary hemangioma. Seven months later, he developed typical features of nonarteritic anterior ischemic optic neuropathy (NAION) in that eye. Such a long latency between "preeruptive" and "eruptive" disc edema has not been well documented in NAION.

Diagnosis, Differential↗

Caught by a masquerade: sclerosing orbital inflammation.

Idiopathic sclerosing inflammation of the orbit is a distinct form of orbital inflammatory disease characterized by slow and relentless involvement of orbital structures. It is this insidious and relentless course that makes distinction from neoplastic lesions clinically difficult. We report the case of a patient with a several-week history of headache and decreased vision that was originally thought to represent an optic nerve sheath meningioma, based on clinical and radiographic evaluation. Subsequent histopathology from an optic nerve biopsy, however, was more consistent with optic nerve glioma. Eventually, pathologic examination of whole sections through the optic nerve was required to establish and confirm the actual diagnosis of sclerosing orbital inflammation.

Adult↗