B Mark Keegan

Mayo Clinic - Rochester, Рочестер, Minnesota, United States

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Publications (70)503.55 Total impact

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    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.
    Neurology 11/2014; 84(1). DOI:10.1212/WNL.0000000000001094 · 8.30 Impact Factor
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    ABSTRACT: Objective: To highlight a specific under-recognized radiological feature of spondylotic myelopathy often resulting in misdiagnosis.Methods: Patients evaluated between 1/1/1996-12/31/2012 who met the following criteria were included: 1) suspected spondylotic myelopathy; 2) gadolinium enhancement detected; 3) spinal surgery performed.Results: Fifty six patients (70% men) whose median age was 53.5 years (range, 24-80) were included. Spinal cord MRI (cervical, 52; thoracic, 4) revealed longitudinal-spindle-shaped-T2-signal hyperintensity (100%) and cord enlargement (79%) accompanied by a characteristic pancake-like 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 accuracy of 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 pre-operatively (p=0.005), but not delay to surgery, predicted need for gait aid at final follow-up.Interpretation: Transverse pancake-like 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. ANN NEUROL 2014. © 2014 American Neurological Association
    Annals of Neurology 07/2014; 76(1). DOI:10.1002/ana.24184 · 11.91 Impact Factor
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    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.
    Nature Clinical Practice Neurology 06/2014; 4(3):226-230. DOI:10.1212/CPJ.0000000000000030 · 7.64 Impact Factor
  • B. Mark Keegan, Eoin P. Flanagan
    Mayo Clinic Proceedings 06/2014; 89(6):859. DOI:10.1016/j.mayocp.2014.03.009 · 5.81 Impact Factor
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    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.
    PLoS ONE 03/2014; 9(3):e90509. DOI:10.1371/journal.pone.0090509 · 3.53 Impact Factor
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    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.
    Mayo Clinic Proceedings 11/2013; 88(11):1204-12. DOI:10.1016/j.mayocp.2013.07.019 · 5.81 Impact Factor
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    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.
    Neurology 10/2013; DOI:10.1212/01.wnl.0000435560.00234.a7 · 8.30 Impact Factor
  • Practical Neurology 05/2013; DOI:10.1136/practneurol-2013-000560
  • B Mark Keegan
    Seminars in Neurology 02/2013; 33(1):3-4. DOI:10.1055/s-0033-1345711 · 1.78 Impact Factor
  • Eoin P Flanagan, B Mark Keegan
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    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.
    Neurologic Clinics 02/2013; 31(1):307-18. DOI:10.1016/j.ncl.2012.09.001 · 1.61 Impact Factor
  • B Mark Keegan
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    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.
    Seminars in Neurology 02/2013; 33(1):5-12. DOI:10.1055/s-0033-1345709 · 1.78 Impact Factor
  • 01/2013; 3(3). DOI:10.1016/j.msard.2013.10.009
  • B Mark Keegan, Sean J Pittock
    Archives of neurology 07/2012; 69(7):819-20. DOI:10.1001/archneurol.2012.1015 · 7.01 Impact Factor
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    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.
    Multiple Sclerosis 06/2012; 19(2). DOI:10.1177/1352458512451510 · 4.86 Impact Factor
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    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.
    Neurosurgery 05/2012; 71(3):581-6; discussion 586. DOI:10.1227/NEU.0b013e31825e795b · 3.03 Impact Factor
  • Neurology 03/2012; 78(10):743-9. DOI:10.1212/WNL.0b013e318248e59c · 8.30 Impact Factor
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    ABSTRACT: Recently, increased attention has been paid to the association of progressive multifocal leukoencephalopathy (PML) with the use of immunomodulatory medications for autoimmune diseases. A 23-year-old Native American woman with a history of systemic lupus erythematosus and erosive polyarthritis treated with prednisone and etanercept presented with focal weakness, hemiataxia, diplopia, and dysarthria. Brain magnetic resonance imaging demonstrated progressive, T2 signal hyperintensities within the brainstem and cerebellar white matter without mass effect or gadolinium enhancement. Cerebrospinal fluid showed elevated protein and JC virus polymerase chain reaction positive with 28,600 copies/ml diagnostic of PML. The development of PML in this patient treated with etanercept and prednisone highlights the increased risk for opportunistic infection with JC virus in patients with autoimmune diseases on immunosuppressive therapies.
    The Neurologist 03/2012; 18(2):85-7. DOI:10.1097/NRL.0b013e318247b868 · 1.08 Impact Factor
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    ABSTRACT: To present a case series of patients with progressive myelopathy in the setting of a solitary demyelinating lesion. We describe 7 patients evaluated over a 6-year period. All had progressive motor impairment attributable to an MRI lesion compatible with a demyelinating plaque in the brainstem or upper cervical spinal cord. At the time of evaluation, none met the International Panel imaging criteria for dissemination in space, and none described clinical symptoms consistent with relapses affecting other portions of the CNS. Lesions identified were in the ventral cervicomedullary junction in 4 patients, the ventral spinal cord in 2 patients, and the pons in 1 patient. Median age at onset was 43 years (range 33-51 years). Median follow-up interval was 3 years (range 2-27 years). Six patients reached an Expanded Disability Status Scale (EDSS) score of 6.0 or worse. Median time to EDSS score of 6.0 was 7.5 years (range 1.5-26 years). Four had CSF findings characteristic of multiple sclerosis (MS). None had CSF, imaging, or serologic evidence of an alternative etiology of progressive myelopathy. In 3 patients, serial MRI scans of the brain and spinal cord demonstrated no accumulation of lesions. Postmortem examination of a fourth patient demonstrated an isolated pontine demyelinating lesion. Solitary demyelinating lesions may produce a progressive myelopathy similar to primary progressive MS. Demyelinating disease should be in the differential diagnosis of progressive myelopathy despite absence of dissemination in space.
    Neurology 02/2012; 78(8):540-4. DOI:10.1212/WNL.0b013e318247cc8c · 8.30 Impact Factor
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    ABSTRACT: Intramedullary spinal cord metastases of solid neoplasms are associated with poor long-term survival. As the characteristics of secondary intramedullary spinal cord non-Hodgkin's lymphoma (NHL) are not well understood, we sought to describe its clinical features and outcome. We retrospectively reviewed the Mayo Clinic patient database, lymphoma database, and pathology records from 1996 to 2010 and identified patients with clinical myelopathy and neuroimaging evidence of secondary intramedullary spinal cord involvement from pathologically confirmed systemic NHL. Seven patients were included in this study. The median age was 61 years (range, 41-81). Symptom onset was subacute (≤8 weeks) in six. Four patients were wheelchair-dependent at diagnosis. Spinal cord NHL was diagnosed by cerebrospinal fluid cytology in four; Positron emission tomography hypermetabolism in two; or MRI features alone. Myelopathy developed in five patients at a median 8 months (range, 1-58) following systemic NHL diagnosis, while myelopathy was the heralding symptom of NHL in two patients. Spinal cord MRI lesions were characteristically gadolinium enhancing and expansile. Four patients had co-existing MRI brain lesions. Six patients had B-cell NHL and one patient T-cell NHL. Six of the seven were treated (high dose intravenous methotrexate in three; radiation therapy in two; and R-CHOP in one). Median survival was 11.5 months (range, 1-28) with a 33% 2-year survival compared to historical median survival estimates of spinal cord metastases due to solid tumors of 3 months. In secondary intramedullary spinal cord involvement of NHL early neurological morbidity is common, but overall survival compares favorably to previously reported survival in spinal cord metastases from solid tumors.
    Journal of Neuro-Oncology 12/2011; 107(3):575-80. DOI:10.1007/s11060-011-0781-4 · 2.79 Impact Factor
  • Neurology 11/2011; 77(19):1756-60. DOI:10.1212/WNL.0b013e318236eec2 · 8.30 Impact Factor

Publication Stats

821 Citations
503.55 Total Impact Points


  • 2002–2014
    • Mayo Clinic - Rochester
      • Department of Neurology
      Рочестер, Minnesota, United States
  • 2009
    • Istanbul University
      • Department of Neuropathology
      İstanbul, Istanbul, Turkey
  • 2008
    • American University of Beirut
      Beyrouth, Beyrouth, Lebanon
  • 2007
    • University of Colorado
      Denver, Colorado, United States
    • University of California, San Francisco
      San Francisco, California, United States
    • University of Wisconsin–Madison
      Madison, Wisconsin, United States
    • Robert Wood Johnson University Hospital
      New Brunswick, New Jersey, United States
    • The University of Western Ontario
      • Department of Clinical Neurological Sciences
      London, Ontario, Canada
    • Drexel University
      Filadelfia, Pennsylvania, United States
    • Harvard University
      Cambridge, Massachusetts, United States