Biomedical subjects
Publications and source records attributed to Steven L Galetta.
We report a woman with anti-Yo-associated cerebellar degeneration, severe eye movement abnormalities, and no evidence of malignancy after 3 years of extensive evaluation. The prominent neuro-ophthalmologic findings suggest brainstem involvement, which may be a novel manifestation of anti-Yo associated paraneoplastic syndrome.
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.
Visual symptoms frequently complicate the course of multiple sclerosis (MS). The ophthalmologist must be familiar with the neuro-ophthalmologic manifestations of MS to facilitate the initial evaluation and treatment of patients. Magnetic Resonance Imaging has become an important tool to confirm the diagnosis of MS or to assess the risk of MS in patients with clinically isolated demyelinating syndromes. This article reviews the neuro-ophthalmologic manifestations of MS and the management issues that arise in early MS.
We report two patients with migraine, acute visual field defects and other neurological symptoms who were found to have high T(2) signal and FLAIR abnormalities on brain MRI in temporal and parieto-occipital regions. In these patients, the apparent diffusion coefficient (ADC) of their lesions was increased, distinguishing these lesions from those of ischemic stroke. Both were ultimately diagnosed with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). We conclude that conventional MRI when used with diffusion-weighted MR imaging may be invaluable in detecting mitochondrial-related CNS dysfunction.
Explore the source record for details and available documents.
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.
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.
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.
BACKGROUND: Within the past 10 years, several immunomodulatory agents (IMAs) have become available for the treatment of relapsing multiple sclerosis (MS), making therapeutic decisions more complex. We performed a systematic review of the literature to assess the efficacy and safety of these agents on physical, inflammatory, and cognitive measures of disease activity. METHODS: We identified relevant studies by searching electronic databases (MEDLINE and Current Contents) from January 1, 1993, through August 31, 2001. We included English-language reports of data from phase 3 trials of interferon beta-1b (Betaseron), 2 preparations of interferon beta-1a (Avonex and Rebif), or glatiramer acetate (Copaxone) for the treatment of relapsing MS. RESULTS: Twenty-one studies met explicit inclusion criteria. Comparison of study results indicated no differences among IMAs regarding their efficacy on relapse-related measures. Interferon beta-1a significantly reduced disability progression, whereas no significant effect of glatiramer acetate or interferon beta-1b on disability progression was seen. On inflammatory measures, all of the IMAs showed reductions in the burden of disease (T2-weighted lesions) to varying degrees. Interferon beta and glatiramer acetate reduced new lesion activity; however, interferon beta had a more profound effect. One interferon beta-1a preparation (Avonex) appeared to reduce brain atrophy, whereas glatiramer acetate showed an effect in 1 of 2 studies. Only Avonex demonstrated efficacy in slowing progression of cognitive dysfunction. CONCLUSIONS: Data show that the IMAs have similar effects on several physical and inflammatory measures. In addition, Avonex has demonstrated efficacy in slowing cognitive progression in relapsing MS. One disadvantage of interferon beta is the possibility of immunogenicity, which may occur more often with subcutaneous administration. The IMAs have similar safety and tolerability profiles.
Explore the source record for details and available documents.
PURPOSE: To examine vision-specific health-related quality of life in a cohort of patients with multiple sclerosis (MS) using the 25-Item National Eye Institute Visual Function Questionnaire (VFQ-25), and to identify content areas for a brief MS-specific vision questionnaire. DESIGN: Cross-sectional survey. METHODS: The VFQ-25 and a modified version of the Optic Neuritis Treatment Trial (ONTT) Patient Questionnaire were administered by in-person interview to 80 patients at the University of Pennsylvania MS Center. Binocular visual acuities were obtained following a standard protocol using retroilluminated Early Treatment Diabetic Retinopathy Study charts. RESULTS: Despite a median binocular visual acuity of 20/16 (20/12.5-20/250), VFQ-25 subscale scores in the MS cohort were significantly lower (worse) compared with those of a published reference group of eye disease-free patients (P =.0001-0.009, two-tailed t tests). Rank-correlations of VFQ-25 composite (overall) scores with visual acuity were modest, but significant (r(s) = 0.33, P =.003), supporting construct validity for VFQ-25 scores in MS populations. Seven additional aspects of self-reported visual dysfunction in MS were also identified. CONCLUSIONS: Patients with MS have a high degree of self-reported visual dysfunction that is not entirely captured by visual acuity. The VFQ-25 is an effective measure of self-reported visual loss in MS. A brief MS-specific vision questionnaire may provide additional useful information when administered concurrently with the VFQ-25 in future investigations of MS and other neuroophthalmologic disorders.
BACKGROUND: It remains controversial whether transcervical thymectomy offers results equivalent to thymectomy by way of a median sternotomy in the treatment of myasthenia gravis. Furthermore, preoperative prognostic factors have not been clearly defined. METHODS: This study is a retrospective chart review and interview of 78 patients completing transcervical thymectomy for myasthenia gravis between 1992 and 1999. RESULTS: There were 24 men and 54 women. Mean age was 40 years (range, 13 to 78 years). Twelve patients were in Osserman class 1, 25 in class 2, 30 in class 3, and 11 in class 4 (mean, 2.5). There was no perioperative mortality and 6 (7.7%) morbidities. Mean length of stay was 1.5 days and mean follow-up, 54.6 months. The crude cumulative complete remission (asymptomatic off medications for 6 months) rate was 39.7% (n = 31). Only 8 patients (10.3%) failed to improve after transcervical thymectomy. Kaplan-Meier estimates of complete remission were 31% and 43% at 2 and 5 years, respectively. Eight patients with thymoma had a 5-year estimated complete remission rate of 75% in contrast to 43% in 38 patients with thymic hyperplasia and 36% in 32 patients with neither thymoma nor hyperplasia (p = 0.01). Twelve patients with ocular myasthenia had a 5-year estimated complete remission rate of 57%, whereas patients with mild-to-moderate (n = 55) or severe (n = 11) generalized symptoms had 5-year complete remission rates of 43% and 30%, respectively (p = 0.21). CONCLUSIONS: Overall, extended transcervical thymectomy offers results that are comparable to those published for the transsternal procedure. Patients with milder disease (including isolated ocular disease) and taking no preoperative immunosuppressive agents appear to experience higher remission rates. In contrast to previous studies, we also find that small thymomas predict better responses to thymectomy.
BACKGROUND: Despite the plenitude of reports concerning partial or complete third nerve palsies, especially as presenting symptoms with posterior communicating artery (PCoA) aneurysms, we present a patient with an unusual variation. CASE DESCRIPTION: A 66-year-old woman presented with progressive right-sided headaches and diplopia and was found to have a partial, pupil-sparing third nerve palsy. A small right-sided PCoA aneurysm, nearly indistinguishable from an infundibulum, was identified on magnetic resonance angiography and subsequent digital subtraction angiography. The third nerve palsy improved before surgical repair of the aneurysm. RESULTS: Microsurgical exploration revealed a small PCoA aneurysm, which was tethered to the third nerve by arachnoid adhesions. Adhesions were lysed and the aneurysm was repaired sparing the PCoA and its branches. The patient's third nerve function recovered completely postoperatively. CONCLUSIONS: Even a very small PCoA aneurysm may present with an improving, pupil-sparing partial third nerve palsy. Selection of patients for imaging studies should take this unusual variant into consideration. We describe the anatomy and potential mechanisms of this pupil-sparing third nerve palsy.
Patients with typical acute monosymptomatic demyelinating optic neuritis should receive gadolinium-enhanced magnetic resonance imaging (MRI) of the brain and orbits to determine if they are at high risk for the subsequent development of clinically definite multiple sclerosis (CDMS). The presence of >or=2 white matter lesions (>or=3 mm in diameter, at least 1 lesion periventricular or ovoid) indicates high risk for CDMS; the following treatment should be considered for such patients: 1. Intravenous methylprednisolone sodium succinate (1 gram IV/day for 3 days) followed by oral prednisone (1 mg/kg/day for 11 days) with 4-day taper (20 mg on day 1, 10 mg on days 2 and 4); 2. Interferon beta 1-a (Avonex 30microg intramuscularly [IM] weekly, or Rebif 22 microg subcutaneously [SQ] weekly). These two drugs have been shown to reduce the short-term risk of CDMS in high risk monosymptomatic patients. In monosymptomatic patients with <2 white matter lesions, and in patients for whom CDMS has been established, IV methylprednisolone treatment followed by oral prednisone should be considered on an individual basis. Treatment in these patients may hasten visual recovery, but does not affect long-term visual outcome. Oral prednisone alone, without prior treatment with IV methylprednisolone, may increase the risk for recurrent optic neuritis and should be avoided.
We provide a comprehensive clinical, radiological and virological analysis of four patients with Epstein-Barr virus (EBV) infection of the nervous system. One patient developed acute myeloradiculitis, one had acute encephalomyeloradiculitis, one had acute meningoencephalomyeloradiculitis and one had a subacute meningomyeloradiculitis. The ability of EBV to affect multiple parts of the entire neuraxis from meninges and brain to the spinal cord and peripheral nerves was evidenced by combinations of stiff neck and mental status changes, as well as patterns of weakness and sensory loss due to transverse myelitis or peripheral nerve disease. The CSF of all four patients contained a pleocytosis, predominantly mononuclear with elevated levels of protein, but a normal glucose level. In the two patients with acute myeloradiculitis and subacute meningomyeloradiculitis, the MRI revealed an increased signal in the spinal cord and lumbosacral roots, but in the two patients with acute encephalomyeloradiculitis and acute meningoencephalomyeloradiculitis, the brain and spinal cord MRIs were normal. In all four patients, EBV DNA, but not cytomegalovirus (CMV), herpes simplex virus (HSV) or varicella-zoster virus (VZV) DNA, was found in the CSF. The antibody pattern in serum was consistent with recent infection, and both EBV immunoglobulin (Ig) M and IgG antibodies, but not antibodies to HSV, VZV or CMV, were found in the CSF. Finally, there were reduced serum/CSF ratios of antibody to EBV, but not to total IgG or albumin, consistent with intrathecal antibody synthesis. None of the four patients died and none had brain swelling or focal changes according to brain MRI. Residual neurological deficits were evident. The two patients with acute myeloradiculitis and acute meningomyeloradiculitis had residual lower extremity weakness, and one of these patients later developed optic neuritis. The patient with acute encephalomyeloradiculitis had a moderate flaccid paraparesis, and the patient with subacute meningomyeloradiculitis was left with sensory loss in the feet. Compared with neurological disease caused by other herpes viruses, the clinical features of acute EBV myeloradiculitis, encephalomyeloradiculitis, encephalomyeloradiculitis and subacute meningomyeloradiculitis are distinctive. Of the eight human herpesviruses, EBV and VZV produce the most protean neurological syndromes. The mechanism by which EBV produces neurological disease is unknown. More correlative pathological, virological and immunological studies are needed in EBV-associated neurological disease.
A 21-year-old man developed an ipsilateral fourth nerve palsy, contralateral hemianopia, and contralateral hemisensory deficit as manifestations of a proximal right posterior cerebral artery aneurysm. This unusual constellation of signs reflects the involvement of the structures that run in the ambient cistern. The fourth nerve palsy and homonymous hemianopia are attributed to compression by the aneurysm. The hemisensory loss is ascribed to compromise of thalamoperforate arteries emanating from a thrombosed portion of the aneurysm.
We report a patient who presented with Balint's syndrome as a manifestation of primary central nervous system angiitis. Clinical findings included simultanagnosia, optic ataxia, and optic apraxia. Pathologic evaluation demonstrated amyloid angiopathy and Alzheimer's plaques. The presence of primary central nervous system angiitis along with amyloid angiopathy and Alzheimer's plaques may not be coincidental. Angiitis may be a foreign body reaction to A4 amyloid deposition.
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.