B Mark Keegan

Mayo Clinic - Rochester, Рочестер, Minnesota, United States

Are you B Mark Keegan?

Claim your profile

Publications (79)553.11 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective To compare longitudinally extensive myelitis in neuromyelitis optica spectrum disorders (NMOSD) and spinal cord sarcoidosis (SCS). Methods We identified adult patients evaluated between 1996-2015 with SCS or NMOSD whose first myelitis episode was accompanied by a spinal cord lesion spanning ≥3 vertebral segments. All NMOSD patients were aquaporin-4-IgG positive and all sarcoidosis cases were pathologically confirmed. Clinical characteristics were evaluated. Spine MRI's were reviewed by two neuroradiologists. Results We studied 71 patients (NMOSD, 37; SCS, 34). Fourteen (47%) SCS cases were initially diagnosed as NMOSD or idiopathic transverse myelitis. Median delay to diagnosis was longer for SCS than NMOSD (5 versus 1.5 months; p<0.01). NMOSD myelitis patients were more commonly women, had concurrent or prior optic neuritis or intractable vomiting episodes more frequently, shorter time to maximum deficit and had systemic autoimmunity more often than SCS (p<0.05). SCS patients had constitutional symptoms, cerebrospinal fluid (CSF) pleocytosis and hilar adenopathy more frequently than NMOSD (p<0.05); CSF hypoglycorrhachia (11%, p=0.25) and elevated angiotensin converting enzyme (18%, p=0.30) were exclusive to SCS. Dorsal cord subpial gadolinium enhancement extending ≥2 vertebral segments and persistent enhancement >2 months favored SCS, and ring-like enhancement favored NMOSD (p<0.05). Maximum disability was similar in both disorders. Interpretation SCS is an under-recognized cause of longitudinally extensive myelitis that commonly mimics NMOSD. We identified clinical, laboratory, systemic and radiologic features that, taken together, help discriminate SCS from NMOSD. This article is protected by copyright. All rights reserved.
    No preview · Article · Dec 2015 · Annals of Neurology
  • W Oliver Tobin · Fredric B Meyer · B Mark Keegan
    [Show abstract] [Hide abstract]
    ABSTRACT: Objective: We aimed to determine the diagnostic yield and safety of posterior fossa parenchymal biopsy. Methods: One-hundred-thirty-six patients who underwent 137 posterior fossa (brainstem or cerebellar) parenchymal biopsies at Mayo Clinic (Rochester, MN) between 1996 and 2009 were identified by chart review. Case histories, radiological, surgical and pathological reports, and safety outcomes were assessed. Results: Posterior fossa parenchymal biopsies were performed on 78 male and 58 female patients of median age, 47 years (IQR 28-61). Preoperative clinical diagnosis in the majority of cases was of a malignant neoplasm. Glial neoplasm (51%) was the most common finding followed by lymphoma (7%) and neurosarcoidosis (7%). Normal tissue or nonspecific changes observed in 28 cases (20%). Three deaths occurred, 2 at time of biopsy (1%) and one due to underlying disease. All deaths occurred in patients who had a cerebellar biopsy. Transient neurological deficits occurred in 15 patients (11%): worsening of presenting symptoms (4), cardiac arrhythmia (3), vertigo (2), diplopia (2), ataxia (3), seizure (1), decreased consciousness (1) and limb numbness (3). Sustained neurological deficits occurred in 3 patients: fourth nerve palsy (1), hemiparesis (1), and facial numbness (1). Conclusions: The diagnostic yield of posterior fossa parenchymal biopsy in Mayo Clinic patients with diverse pathologies was 80%. The complication rate was 11% with the majority being transient but 2 deaths occurred attributed to biopsy. Evaluation of the diagnostic yield and complication rate at individual neurosurgical centers is needed to determine generalizability of these results.
    No preview · Article · Sep 2015 · World Neurosurgery
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To evaluate the relationship between early relapse recovery and onset of progressive multiple sclerosis (MS). We studied a population-based cohort (105 patients with relapsing-remitting MS, 86 with bout-onset progressive MS) and a clinic-based cohort (415 patients with bout-onset progressive MS), excluding patients with primary progressive MS. Bout-onset progressive MS includes patients with single-attack progressive and secondary progressive MS. "Good recovery" (as opposed to "poor recovery") was assigned if the peak deficit of the relapse improved completely or almost completely (patient-reported and examination-confirmed outcome measured ≥6 months post relapse). Impact of initial relapse recovery and first 5-year average relapse recovery on cumulative incidence of progressive MS was studied accounting for patients yet to develop progressive MS in the population-based cohort (Kaplan-Meier analyses). Impact of initial relapse recovery on time to progressive MS onset was also studied in the clinic-based cohort with already-established progressive MS (t test). In the population-based cohort, 153 patients (80.1%) had on average good recovery from first 5-year relapses, whereas 30 patients (15.7%) had on average poor recovery. Half of the good recoverers developed progressive MS by 30.2 years after MS onset, whereas half of the poor recoverers developed progressive MS by 8.3 years after MS onset (p = 0.001). In the clinic-based cohort, good recovery from the first relapse alone was also associated with a delay in progressive disease onset (p < 0.001). A brainstem, cerebellar, or spinal cord syndrome (p = 0.001) or a fulminant relapse (p < 0.0001) was associated with a poor recovery from the initial relapse. Patients with MS with poor recovery from early relapses will develop progressive disease course earlier than those with good recovery. © 2015 American Academy of Neurology.
    Full-text · Article · Jul 2015 · Neurology
  • [Show abstract] [Hide abstract]
    ABSTRACT: Summary Neurosarcoidosis mimics many neurologic diseases and poses a major diagnostic challenge. Blind conjunctival biopsy is often used to help diagnose neurosarcoidosis when biopsy of affected nervous system tissue is not feasible. While this test is relatively inexpensive and well-tolerated, the diagnostic yield in patients with inflammatory nervous system disease of unknown etiology remained uncertain. We evaluated 440 patients who underwent conjunctival biopsy due to concern for neurosarcoidosis. Only a small minority of patients (3%) had positive conjunctival biopsies consistent with sarcoidosis, and some patients (1%) with positive biopsies were found to have a cause for their neurologic disease other than neurosarcoidosis. Many patients (14%) had negative conjunctival biopsies but were later confirmed to have neurosarcoidosis after additional evaluations. This study demonstrates that conjunctival biopsy has a low diagnostic yield for neurosarcoidosis in patients with inflammatory nervous system disease and suggests that alternative diagnostic means should be pursued.
    No preview · Article · Jun 2015 · Neurology: Clinical Practice (Print)
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Objective: We examined the effect of relapses-before and after progression onset-on the rate of postprogression disability accrual in a progressive multiple sclerosis (MS) cohort. Methods: We studied patients with primary progressive MS (n = 322) and bout-onset progressive MS (BOPMS) including single-attack progressive MS (n = 112) and secondary progressive MS (n = 421). The effect of relapses on time to Expanded Disability Status Scale (EDSS) score of 6 was studied using multivariate Cox regression analysis (sex, age at progression, and immunomodulation modeled as covariates). Kaplan-Meier analysis was performed using EDSS 6 as endpoint. Results: Preprogression relapses (hazard ratio [HR]: 1.63; 95% confidence interval [CI]: 1.34-1.98), postprogression relapses (HR: 1.37; 95% CI: 1.11-1.70), female sex (HR: 1.19; 95% CI: 1.00-1.43), and progression onset after age 50 years (HR: 1.47; 95% CI: 1.21-1.78) were associated with shorter time to EDSS 6. Postprogression relapses occurred in 29.5% of secondary progressive MS, 10.7% of single-attack progressive MS, and 3.1% of primary progressive MS. Most occurred within 5 years (91.6%) after progressive disease onset and/or before age 55 (95.2%). Immunomodulation after onset of progressive disease course (HR: 0.64; 95% CI: 0.52-0.78) seemingly lengthened time to EDSS 6 (for BOPMS with ongoing relapses) when analyzed as a dichotomous variable, but not as a time-dependent variable. Conclusions: Pre- and postprogression relapses accelerate time to severe disability in progressive MS. Continuing immunomodulation for 5 years after the onset of progressive disease or until 55 years of age may be reasonable to consider in patients with BOPMS who have ongoing relapses.
    Full-text · Article · Nov 2014 · Neurology
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective: To highlight a specific under-recognized radiological feature of spondylotic myelopathy often resulting in misdiagnosis. Methods: Patients evaluated between January 1, 1996 and December 31, 2012 who met the following criteria were included: (1) spondylotic myelopathy was suspected, (2) gadolinium enhancement was detected, and (3) spinal surgery was performed. Results: Fifty-six patients (70% men) whose median age was 53.5 years (range = 24-80) were included. Spinal cord magnetic resonance imaging (cervical in 52; thoracic in 4) revealed longitudinal spindle-shaped T2-signal hyperintensity (100%) and cord enlargement (79%) accompanied by a characteristic pancakelike transverse band of gadolinium enhancement in 41 (73%), typically immediately caudal to the site of maximal spinal stenosis. Forty (71%) patients were initially diagnosed with neoplastic or inflammatory myelopathies, and decompressive surgery was delayed by a median of 11 months (range = 1-64). Spinal cord biopsy in 6 did not reveal any alternative diagnosis. Ninety-five percent were stable or improved. Gadolinium enhancement persisted in 75% at 12 months, raising concern about the accuracy of the initial diagnosis. Twenty patients required a gait aid (36%) at last follow-up (median = 60 months, range = 10-172). The need for a gait aid preoperatively (p = 0.005), but not delay of surgery, predicted the need for gait aid at final follow-up. Interpretation: Transverse pancakelike gadolinium enhancement associated with and just caudal to the site of maximal stenosis and at the rostrocaudal midpoint of a spindle-shaped T2 hyperintensity suggests that spondylosis is the cause of the myelopathy. Persistent enhancement for months to years following decompressive surgery is common. Recognition is important to prevent inappropriate interventions or delay in consideration of a potentially beneficial decompressive surgery.
    No preview · Article · Jul 2014 · Annals of Neurology
  • Eoin P Flanagan · David S Knopman · B Mark Keegan
    [Show abstract] [Hide abstract]
    ABSTRACT: Distinguishing dementia due to multiple sclerosis (MS) from that of an accompanying neurodegenerative dementia coexisting with MS has been difficult. The recent introduction of Alzheimer disease (AD) biomarkers of amyloid-β and neuronal degeneration has improved diagnosis of AD premortem. We describe 3 patients with MS with coexisting AD, 1 diagnosed at autopsy before AD biomarkers were available and 2 diagnosed premortem by decreased CSF amyloid-β1-42/tau index, MRI, and (18)F-flourodeoxyglucose-PET patterns. AD biomarkers may be of diagnostic value in selected patients with severe dementia and MS.
    No preview · Article · Jun 2014 · Nature Clinical Practice Neurology
  • B. Mark Keegan · Eoin P. Flanagan

    No preview · Article · Jun 2014 · Mayo Clinic Proceedings
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: To report the 5-year risk and to identify risk factors for the development of a seminal acute or progressive clinical event in a multi-national cohort of asymptomatic subjects meeting 2009 RIS Criteria. Retrospectively identified RIS subjects from 22 databases within 5 countries were evaluated. Time to the first clinical event related to demyelination (acute or 12-month progression of neurological deficits) was compared across different groups by univariate and multivariate analyses utilizing a Cox regression model. Data were available in 451 RIS subjects (F: 354 (78.5%)). The mean age at from the time of the first brain MRI revealing anomalies suggestive of MS was 37.2 years (y) (median: 37.1 y, range: 11-74 y) with mean clinical follow-up time of 4.4 y (median: 2.8 y, range: 0.01-21.1 y). Clinical events were identified in 34% (standard error = 3%) of individuals within a 5-year period from the first brain MRI study. Of those who developed symptoms, 9.6% fulfilled criteria for primary progressive MS. In the multivariate model, age [hazard ratio (HR): 0.98 (95% CI: 0.96-0.99); p = 0.03], sex (male) [HR: 1.93 (1.24-2.99); p = 0.004], and lesions within the cervical or thoracic spinal cord [HR: 3.08 (2.06-4.62); p = <0.001] were identified as significant predictors for the development of a first clinical event. These data provide supportive evidence that a meaningful number of RIS subjects evolve to a first clinical symptom. An age <37 y, male sex, and spinal cord involvement appear to be the most important independent predictors of symptom onset.
    Full-text · Article · Mar 2014 · PLoS ONE
  • [Show abstract] [Hide abstract]
    ABSTRACT: To report and compare spinal cord [(18)F]-fluorodeoxyglucose-positron emission tomography (FDG-PET) metabolism in 51 patients with active myelopathy. We retrospectively identified patients from January 1, 2001, through December 31, 2011, with active myelopathy in whom FDG-PET was performed. Inclusion criteria were (1) intramedullary myelopathy, (2) neoplastic/inflammatory etiology, and (3) FDG-PET performed after myelopathy onset. Exclusion criteria were (1) extramedullary myelopathy, (2) radiation-associated myelopathy, (3) no pathological confirmation of neoplasm, and (4) inactive myelopathy. Diagnostic categories of nonsarcoid inflammatory, neoplastic, and neurosarcoid were based on their final myelopathic diagnosis. Two radiologists who independently assessed FDG-PET for spinal cord hypermetabolism and maximum standardized uptake value (SUVmax) were blinded to the underlying etiology. Fifty-one patients (53% women) with a median age of 60 years (range, 20-82 years) were included. Inflammatory myelopathic diagnoses (n=24) were as follows: paraneoplastic (n=13), autoimmune/other (n=5), inflammatory demyelinating (n=4), and transverse myelitis (n=2). Neoplastic diagnoses (n=21) were as follows: intramedullary metastases (n=12), intramedullary lymphoma/leukemia (n=7), and primary intramedullary neoplasm (n=2). Six patients had neurosarcoid myelopathy. Spinal cord hypermetabolism was more common with neoplastic myelopathy than with nonsarcoid inflammatory myelopathy (17 of 21 [81%] vs 6 of 24 [25%]; P<.001). Agreement between radiologist's assessments was excellent (κ=0.88). Median SUVmax was greater in neoplastic than in nonsarcoid inflammatory causes of myelopathy (3.3 g/mL vs 1.9 g/mL; P<.001). The FDG-PET hypermetabolism was seen in 3 of the 6 patients (50%) with neurosarcoid myelopathy (median SUVmax, 2.6 g/mL; range, 1.8-12.2 g/mL). Spinal cord FDG-PET hypermetabolism in patients with active myelopathy may be reliably detected and was more common in neoplastic than in inflammatory myelopathies in this study. Future investigation of spinal cord FDG-PET is indicated to assess its potential contributions in evaluating active myelopathies.
    No preview · Article · Nov 2013 · Mayo Clinic Proceedings
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: A 59-year-old man had a 2-month history of nonfluctuating encephalopathy. He initially presented acutely with fevers, headaches, and word-finding difficulties. The sedimentation rate was elevated with a bland CSF and normal MRI head. Body CT showed diffuse pulmonary interstitial thickening with patchy opacification. Following treatment for pneumonia, there was resolution of fevers. No infectious etiology was identified. Within days of discharge, he developed bilateral uveitis, which was successfully treated with corticosteroid eyedrops and oral acyclovir. One month later, he developed confusion and unsteadiness. Repeat MRI was reportedly normal; body CT showed resolution of lung changes but diffuse lymphadenopathy persisted. A lymph node biopsy, reviewed at our institution, showed nonspecific reactive changes and fibrosis. Due to progressive encephalopathy and worsening headaches 2 months after symptom onset, the patient presented to our institution. On examination, he scored 30/38 on the Kokmen short test of mental status,(1) losing points for attention and immediate and delayed recall. Funduscopy revealed bilateral disc edema. He had mild appendicular ataxia and impaired tandem walk. The remainder of the examination was normal.
    Full-text · Article · Oct 2013 · Neurology

  • No preview · Article · Oct 2013 · Neurology: Clinical Practice (Print)
  • Eoin P Flanagan · Timothy J Kaufmann · B Mark Keegan

    No preview · Article · May 2013 · Practical Neurology
  • B Mark Keegan

    No preview · Article · Feb 2013 · Seminars in Neurology
  • Eoin P Flanagan · B Mark Keegan
    [Show abstract] [Hide abstract]
    ABSTRACT: Paraneoplastic causes are a rare but important diagnostic consideration when evaluating myelopathy because neurologic symptoms may herald a diagnosis of cancer. Spinal cord MRI findings of longitudinally extensive, symmetric, tract-specific T2-signal changes occasionally with gadolinium enhancement are characteristic. Detection of neural-specific autoantibodies assists in confirming the diagnosis and guides the cancer search. Initial management involves detection and treatment of the underlying cancer. Combinations of immunotherapies are typically recommended but evidence-based therapeutic guidelines are lacking and morbidity remains high. Autoimmune myelopathies may also occur in association with neural-specific autoantibodies without an underlying cancer and in association with systemic autoimmune disorders.
    No preview · Article · Feb 2013 · Neurologic Clinics
  • B Mark Keegan
    [Show abstract] [Hide abstract]
    ABSTRACT: Multiple sclerosis is a presumed autoimmune, inflammatory disease of the central nervous system. Since the early 1990s, medications have been devised, tested, and approved for relapsing forms of multiple sclerosis (MS). MS treatments work by altering the immune system to reduce inflammatory MS activity, thus curtailing clinical relapses (attacks), thereby reducing short-term disability related to the MS attacks. The promise of long-term improvement in MS-related disability remains the most desirable therapeutic goal; to what degree current MS therapies are effective in reducing this is controversial. Recent years have seen a surge in novel MS therapies delivered both parenterally and orally that offer new therapeutic alternatives to MS patients and their treating providers. It remains essential to make an unequivocal diagnosis of MS and identify its clinical course prior to initiating therapies. Switching and altering MS therapies can now be done by rational approaches based on therapeutic efficacy and tolerability; however, these remain nonevidence-based for the most part. The high cost of MS therapies remains a significant concern. A new therapeutic era is at hand offering new hope for patients affected by this chronic, frequently disabling disease.
    No preview · Article · Feb 2013 · Seminars in Neurology
  • Source
    Jan-Mendelt. Tillema · Deborah Renaud · B. Mark Keegan

    Full-text · Article · Jan 2013 · Multiple Sclerosis and Related Disorders
  • B Mark Keegan · Sean J Pittock

    No preview · Article · Jul 2012 · Archives of neurology
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background:It is unclear if all patients with relapsing-remitting multiple sclerosis (RRMS) ultimately develop progressive MS. Onset of progressive disease course seems to be age- rather than disease duration-dependent. Some forms of progressive MS (e.g. primary progressive MS (PPMS)) are uncommon in population-based studies. Ascertainment of patients with PPMS from clinic-based populations can facilitate a powerful comparison of age at progression onset between secondary progressive MS (SPMS) and PPMS but may introduce unclear biases.Objective:Our aim is to confirm that onset of progressive disease course is more relevant to the patient's age than the presence or duration of a pre-progression relapsing disease course in MS.Methods:We studied a population-based MS cohort (n=210, RRMS n=109, progressive MS n=101) and a clinic-based progressive MS cohort (n=754). Progressive course was classified as primary (PPMS; n=322), single attack (SAPMS; n=112) and secondary progressive (SPMS; n=421). We studied demographics (chi(2) or t-test), age-of-progression-onset (t-test) and time to Expanded Disability Status Scale of 6 (EDSS6) (Kaplan-Meier analyses).Results:Sex ratio (p=0.58), age at progression onset (p=0.37) and time to EDSS6 (p=0.16) did not differ between the cohorts. Progression had developed before age 75 in 99% of patients with known progressive disease course; 38% with RRMS did not develop progression by age 75. Age at progression onset did not differ between SPMS (44.9±9.6), SAPMS (45.5±9.6) and PPMS (45.7±10.8). In either cohort, only 2% of patients had reached EDSS6 before onset of progression.Conclusions: PATIENTS: with RRMS do not inevitably develop a progressive disease course. Onset of progression is more dependent on age than the presence or duration of a pre-progression symptomatic disease course. Moderate disability is sustained predominantly after the onset of a progressive disease course in MS.
    No preview · Article · Jun 2012 · Multiple Sclerosis
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Approximately 1% to 2% of patients with multiple sclerosis (MS) develop trigeminal neuralgia (TN). Percutaneous surgery is commonly performed in medically refractory cases. To analyze the pain outcomes and complications of patients with MS-related trigeminal neuralgia (MS-TN) having percutaneous surgery. Patients having balloon microcompression (BMC; n = 69) or glycerol rhizotomy (PRGR; n = 67) from 1997 to 2010 were reviewed retrospectively. Patients in the 2 groups were similar with regard to age, sex, pain location, and pain quality. Mean pain duration was longer in the PRGR group (54.6 vs 16 months; P < .001); more patients having BMC had prior surgery (87% vs. 48%; P < .001). Outcomes were defined as excellent (no pain, no medications), good (no pain with medications), and poor. Median follow-up was 13 months (range, 0.25-132 months). Ninety-five patients initially had excellent (n = 45, 33%) or good (n = 50, 37%) outcomes. Pain relief was maintained in 58% of patients at 3 months and 28% at 2 years. There was no difference in excellent/good outcomes between the surgical groups (hazard ratio = 0.73; P = .14). No correlation was noted between pain relief and new or increased facial numbness (hazard ratio = 0.78; P = .19). Forty-four BMC patients (64%) had additional surgery compared with 36 PRGR patients (54%; P = .19). Complications were more frequent after BMC (17.4% vs 3.0%; P < .01). Percutaneous surgery for patients with MS-TN is less likely to provide pain relief than similar operations performed for patients with idiopathic TN. New trigeminal deficits did not correlate with better facial pain outcomes, supporting the concept that many patients with MS-TN have centrally mediated pain.
    Full-text · Article · May 2012 · Neurosurgery