Leo Wolansky

Efficacy of treatment of MS with IFNβ-1b or glatiramer acetate by monthly brain MRI in the BECOME study

Background: There are no published MRI studies comparing interferon beta 1b (IFNβ-1b) and glatiramer acetate (GA) for treatment of relapsing multiple sclerosis (MS). Objective: To compare the efficacy of IFNβ-1b and GA for suppression of MS disease activity as evidenced on frequent brain MRI. Methods: A total of 75 patients with relapsing-remitting MS or clinically isolated syndromes were randomized to standard doses of IFNβ-1b or GA and followed by monthly brain MRI for up to 2 years with a protocol optimized to detect enhancement. The primary outcome was the number of combined active lesions (CAL) per patient per scan during the first year, which included all enhancing lesions and nonenhancing new T2/fluid-attenuated inversion recovery (FLAIR) lesions. Secondary outcomes were the number of new lesions and clinical exacerbations over 2 years. Results: Baseline characteristics were similar between the groups. The primary outcome showed similar median (75th percentile) CAL per patient per scan for months 1–12, 0.63 (2.76) for IFNβ-1b, and 0.58 (2.45) for GA (p = 0.58). There were no differences in new lesion or clinical relapses for 2 years. Only 4.4% of CAL on monthly MRI scans were nonenhancing new T2/FLAIR lesions. Conclusion: Patients with relapsing multiple sclerosis randomized to interferon beta 1b or glatiramer acetate showed similar MRI and clinical activity.

MRI of pituitary abscess: two cases and review of the literature

Abstract Pituitary abscesses, rare lesions, may be divided into primary and secondary types. Primary pituitary abscesses occur within a previously healthy gland, while secondary abscesses arise within an existing lesion, such as an adenoma, craniopharyngioma, or Rathkes cleft cyst. Secondary abscesses share radiologic characteristics with the lesions from which they arise. There has been no review of the MRI characteristics of primary pituitary abscesses. We report two cases and review the literature. The typical primary pituitary abscess gives the same or slightly lower signal than brain on T1-weighted images, and could be mistaken for a solid mass or presumed to represent a pituitary adenoma. Contrast-enhanced images are useful, demonstrating absence of central enhancement, suggesting a fluid or necrotic center. In one of our cases, meningeal enhancement was obvious; this has not been reported previously and may be diagnostic, when associated with a rim-enhancing pituitary mass.

Surgical anatomy of the vertebral arteries.

Study Design This study compared direct measurements of the distances between the vertebral arteries in the cervical spines of human cadaver specimens with data obtained from axial computed tomography images of these specimens. Objective To determine whether the information obtained from a computed tomography scan can be used reliably to predict the true anatomic location of the vertebral arteries and, in so doing, provide accurate guidelines for the lateral extent of anterior cervical decompressive procedures. Summary of Background Data Iatrogenic vertebral artery injury during anterior cervical surgery is uncommon, potentially catastrophic, and avoidable. Methods The means and standard deviation of measurements of the location of the cervical segment of the vertebral arteries obtained with high‐precision, digital calipers by direct gross anatomic dissection of 16 adult (eight male, eight female) cadaver specimens were recorded. These measurements were compared with computed tomography scan data obtained on the same specimens. Results The mean distances between the vertebral arteries progressively increased from C3 to C6. Computed tomography scan measurements of the distance between the cervical foramina transversaria were consistently smaller than direct measurements of the gross specimens. At C6, the computed tomography scan data were significantly less than the gross anatomic data. Conclusions According to these data, computed tomography scan measurements may be used safely and accurately to plan the lateral extent of anterior cervical decompressive surgical procedures. Although the data obtained from the gross anatomic dissections may serve as guidelines to assist the surgeon, the authors recommend a careful review of the preoperative computed tomography scan on an individual case‐by‐case basis as the safest method to plan for anterior cervical surgery.

Serum levels of CXCL13 are elevated in active multiple sclerosis.

There is increasing recognition of the important role that B cells play in the pathogenesis of multiple sclerosis (MS). Recently it was reported that the B cell chemokine CXCL13 is elevated in MS serum and cerebrospinal fluid. Here we study whether serum levels of CXCL13 are associated with active MS. We measured serum levels of CXCL13 by enzyme-linked immunosorbent assay in 74 patients with relapsing MS randomized to interferon beta 1b or glatiramer acetate and examined with monthly 3 T brain MRI scans optimized for detection of gadolinium-enhancement for up to 2 years. The median (range) serum levels of CXCL13 pre-treatment were 40 (3—171) pg/ml. Serum levels of CXCL13 were significantly higher at times of active brain MRI scans (p < 0.01). Furthermore, serum levels were higher in patients who never reached MRI remission compared with those in complete (p < 0.01) or partial (p = 0.01) remission. There was a significant positive correlation between the pattern of serum levels of CXCL13 and MRI activity during the first (r = 0.33, p < 0.05) and the full 2 years (r = 0.35, p < 0.01) of the study. Treatment with interferon beta 1b or glatiramer acetate did not affect serum CXCL13. We conclude that the serum levels of the B cell chemokine CXCL13 are associated with active MS.

Candidal Pituitary Abscess: Case Report

We report a case of a culture-proven intrasellar Candida albicans abscess. A 36-year-old woman presented with a history of headaches, menstrual irregularities, and mild symptoms of diabetes insipidus. She was neurologically intact at the time of a transsphenoidal surgery for a presumed pituitary adenoma. An extensive work-up revealed that although the patient was seronegative for human immunodeficiency virus, she was immunocompromised with a T-cell dysfunction. Fungal abscesses of the pituitary gland have rarely been reported. This is the first documented case of a patient who is seronegative for human immunodeficiency virus who becomes infected by an ordinarily innocuous fungus, Candida albicans.

New acute and chronic black holes in patients with multiple sclerosis randomised to interferon beta-1b or glatiramer acetate

Background: Hypointense lesions on T1 weighted MRI, referred to as black holes (BH), are a marker of demyelination/axonal loss in multiple sclerosis (MS). There is some evidence that glatiramer acetate (GA) may decrease the conversion of new brain lesions to BH. Methods: Monthly 3-Tesla brain MRI scans were used for up to 2 years to study the development and evolution of new BH in 75 patients with MS randomised to GA or Interferon β-1b (IFNβ1b) in the BECOME study. Findings: Of 1224 newly enhancing lesions (NEL) appearing at baseline through 24 months in 61 patients, 767 (62.7%) showed an acute BH (ABH). The majority of ABH were transient and of similar duration by treatment group. Of 571 ABH in which MRI follow-up scans were available for ⩾1 year, 103 (18.8%) were still visible ⩾12 months after onset and were considered chronic BH (CBH). Only 12.1% of the 849 NEL with MRI follow-up ⩾1 year converted to CBH, 9.8% with IFNβ1b and 15.2% with GA (p = 0.02). The conversion from ABH to CBH was also lower with IFNβ1b (15.2%) than with GA (21.4%), of borderline significance (p = 0.06). The majority of patients who developed NEL did not develop CBH; however, about a quarter had conversion rates from ABH to CBH greater than 20%. Interpretation: Only a minority of new brain lesions in patients with MS treated with GA or IFNβ1b convert to CBH.

Triple-dose versus single-dose gadoteridol in multiple sclerosis patients.

Nine patients with multiple sclerosis underwent brain magnetic resonance imaging (MRI) to evaluate the contrast enhancement of individual lesions after a single dose and a triple dose of gadolinium. A single dose (0.1 mmol/kg) of gadoteridol was administered and after a delay, axial T1‐weighted images were obtained. After an additional 0.2‐mmol/kg dose, the same T1‐weighted sequence was repeated. An unblinded reader simultaneously viewed the images from both doses, and utilizing a computer console to rule out flow artifacts, created a gold standard of “definite” enhancing lesions. Using this system, he determined that there was a total of 12 definite enhancing lesions among the patients. This reader also evaluated lesion conspicuity. The contrast‐noise ratio was calculated for each lesion. A second reader, blinded to the dose used, then evaluated the number of enhancing lesions at both doses. The unblinded reader noted increased lesion conspicuity after the triple dose. Contrast‐noise ratios were significantly (p < 0.001) higher after the triple dose (mean, 9.19) than after the single dose (mean, 2.97). The blinded reader detected 11 of the 12 definite lesions on MRis after the triple dose (sensitivity, 92 %) but saw only 6 on MRis after the single dose (sensitivity, 50%). The difference was significant (p < 0.001 ). Subjective analysis of the films revealed an increase in “ghosting artifacts” at the high dose. Administration of tripledose gadolinium provides increased lesion conspicuity and an improved lesion detection rate when compared to single‐dose gadolinium in patients with multiple sclerosis.

Candidal Pituitary Abscess

We report a case of a culture-proven intrasellar Candida albicans abscess. A 36-year-old woman presented with a history of headaches, menstrual irregularities, and mild symptoms of diabetes insipidus. She was neurologically intact at the time of a transsphenoidal surgery for a presumed pituitary adenoma. An extensive work-up revealed that although the patient was seronegative for human immunodeficiency virus, she was immunocompromised with a T-cell dysfunction. Fungal abscesses of the pituitary gland have rarely been reported. This is the first documented case of a patient who is seronegative for human immunodeficiency virus who becomes infected by an ordinarily innocuous fungus, Candida albicans.

Reversible blindness resulting from optic chiasmitis secondary to systemic lupus erythematosus

Objective To report the diagnosis, radiologic findings, and therapy of a 51-year-old female with systemic lupus erythematosus (SLE) who, while on hydroxychloroquine maintenance therapy, presented with a junctional scotoma indicative of chiasmal disease. This visual loss developed after she had been tapered off corticosteroids. Materials and Methods An interventional case report of a female that was given acute therapy with 1-gram daily of intravenous methylprednisolone sodium succinate for 5 days, followed by maintenance methotrexate and a slow taper of oral prednisone. Magnetic resonance imaging (MRI) scans, visual acuity, color vision, and threshold visual fields were performed. Results The MRI scan showed chiasmal involvement, which may occur in SLE in absence of any other evidence of systemic activity. Therapy led to visual function returning to 20/20 OD and 20/20 OS, with normal Ishihara plates OU and only minimal paracentral depressions OU. She has been able to be weaned off prednisone while on methotrexate maintenance. Conclusions Chiasmal involvement may occur in SLE in absence of any other evidence of systemic activity. Maintenance with hydroxychloroquine may not be adequate to prevent this rare cause of visual loss in SLE. Aggressive therapy of chiasmal involvement in SLE, even when the visual loss is profound, may lead to visual restoration, which was virtually complete in this case. Methotrexate may be an alternate agent for patients who break through with optic neuropathy while on hydroxychloroquine.

Effect of anti-IFNβ antibodies on MRI lesions of MS patients in the BECOME study

Background: Interferon beta (IFNβ) administered subcutaneously is immunogenic in some patients with multiple sclerosis (MS) and leads to the development of neutralizing antibodies (NAbs). Considerable evidence has accumulated that NAbs diminish or abolish IFNβ bioactivity, but there is less evidence that NAbs impact clinical efficacy of the drug. Methods: Because a robust effect of IFNβ is a decrease in enhancing lesions on brain MRI scans, the Betaseron Copaxone in Multiple Sclerosis With Triple-Dose Gadolinium and 3-Tesla MRI Endpoints (BECOME) study, a head-to-head study of IFNβ-1b vs glatiramer acetate with a primary endpoint of enhancing lesions on MRI, provided an excellent opportunity to determine the effect of NAbs on MRI activity. We measured NAbs and IFNβ bioactivity by myxovirus resistance protein A gene expression and identified 2 groups of patients: one labeled “bioactivity preserved,” with absent NAbs and robust IFNβ bioactivity (n = 8), and the other labeled “bioactivity lost,” with high levels of NAbs and diminished bioactivity (n = 7). The development of enhancing lesions in the groups was then compared. Results: The incidence of NAbs and effect of NAbs on bioactivity were consistent with previous studies. We analyzed MRI outcomes in patients with NAbs at levels high enough to abolish bioactivity relative to patients without NAbs. For the preserved bioactivity group, the enhancing lesion/scan ratio decreased from 7.6 in the pretreatment period to 2.6 in the posttreatment period, a 66% decrease. For the lost bioactivity group, the decrease was 8.5 to 5.8, only a 32% decrease. Thus, lost bioactivity from high levels of NAbs resulted in reduced therapeutic efficacy of IFNβ as manifested by diminished reductions in enhancing lesions on MRI. Conclusions: High levels of anti–interferon beta (IFNβ) antibodies, which result in diminished bioactivity, are correlated with reduced therapeutic efficacy of IFNβ.