F Graus

Hospital de la Santa Creu i Sant Pau, Barcino, Catalonia, Spain

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Publications (429)2321.88 Total impact

  • Lidia Sabater · Albert Saiz · Josep Dalmau · Francesc Graus
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    ABSTRACT: CV2 antibodies (CV2-ab) associate with paraneoplastic neurological syndromes (PNS) and small-cell lung cancer. This study was designed to assess the sensitivity of two widely used anti-CV2 commercial kits. Fifty three sera with CV2-ab identified by immunohistochemistry on paraformaldehyde-perfused rat brain were tested with two commercial immunoblot kits (Euroimmun AG, and Ravo Diagnostika) and 4 (7.5%) of them were negative with the commercial kits. The 4 samples were positive by immunofluorescence on HEK293 cells transfected with CRMP5 and immunoblot of these cells lysate. A few CV2-ab-positive sera may be missed by commercial immunoblots. Negative samples from patients with high suspicion for PNS should be tested by alternative methods.
    No preview · Article · Jan 2016
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    ABSTRACT: Introduction: Spondylotic myelopathy is the commonest cause of nontraumatic myelopathy. Radiological features of spondylotic myelopathy can often overlap with inflammatory myelopathies which may lead to a delayed or incorrect diagnosis and therapy. A distinctive gadolinium enhancement pattern recently described may help to differentiate spondylotic from inflammatory myelopathy. Case reports: Case 1: a 38-years-old man presented with a 2-year history of paresthesias in the upper extremities, and one year later cramps on the right limbs and numbness over right C5 and C6 dermatomes, related to movement of the neck. Case 2: a 44-year-old man presented with a 1-year history of progressive gait difficulties and sensory disturbance in the hands, and a recent onset of bladder dysfunction. In both cases, spinal cord MRI identified a longitudinal cervical T2-signal hyperintensity associated with a pancakelike transverse band of gadolinium enhancement just below the site of maximum spinal stenosis, and circumferential or hemicord enhancement on axial images. Conclusions: The radiological features of spondylotic myelopathy may resemble those of inflammatory origin. The recognition of a transverse pancakelike gadolinium enhancement immediately below the site of maximal compression as a typical radiological pattern of spondylotic myelopathy is important to reduce the risk of misdiagnosis and to help in the management of these patients.
    Full-text · Article · Nov 2015 · Revista de neurologia
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    ABSTRACT: In sporadic Creutzfeldt-Jakob disease (sCJD), high signal intensity in fluid attenuated inversion recovery (FLAIR) and diffusion-weighted imaging (DWI) sequences in striatum and/or cortical regions of the brain are present in about 83% of cases, reflecting tissue damage, such as spongiform change and abnormal prion protein deposits. Novel diffusion sequences of MRI might improve the detection of CJD characteristic changes in the subset of patients in whom these alterations are absent or less evident. We report a neuropathologically confirmed case of the rare MM2 T + C subtype of sCJD, with mixed clinical and neuropathological features of MM2 thalamic and MM2 cortical subtypes, in whom the use of diffusion tensor imaging helped to identify cortical hyperintensities that could be easily overlooked with conventional DWI.
    No preview · Article · Nov 2015 · Neuropathology
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    ABSTRACT: Background: Rapidly progressive dementia (RPD) is caused by a heterogeneous group of both neurodegenerative and non-neurodegenerative disorders. The presence of concomitant pathologies, mainly Alzheimer's disease (AD), may act as a confounding variable in the diagnostic process of this group of diseases. Objectives: We aimed to describe clinicopathological features, including Alzheimer's co-pathology, and diagnostic accuracy in a postmortem series of RPD. Methods: Retrospective analysis of 160 brain donors with RPD (defined as 2 years of disease duration from the first symptom to death) registered at the Neurological Tissue Bank of the Biobanc-Hospital Clínic-IDIBAPS, from 2001 to 2011. Results: Prion diseases were the most frequent neuropathological diagnosis (67%), followed by non-prion neurodegenerative pathologies (17%), mostly AD and dementia with Lewy bodies, and non-neurodegenerative diseases (16%). We observed clinicopathological diagnostic agreement in 94% of the patients with prion RPD but only in 21% of those with non-prion RPD. Four patients with potentially treatable disorders were diagnosed, while still alive, as having Creutzfeldt-Jakob disease. Concomitant pathologies were detected in 117 (73%). Among all RPD cases, 51 presented moderate or frequent mature β-amyloid plaques (neuritic plaques), which are considered to be associated with positive amyloid biomarkers in vivo. Conclusions: Prion diseases were accurately identified in our series. In contrast, non-prion RPD diagnosis was poor while the patients were still alive, supporting the need for better diagnostic tools and confirmatory neuropathological studies. The presence of concomitant AD pathology in RPD should be taken into account in the interpretation of amyloid biomarkers.
    Full-text · Article · Nov 2015 · Neurodegenerative Diseases
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    Preview · Article · Nov 2015 · Neuro-Oncology
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    ABSTRACT: Objective: To report 14 patients with immune-mediated relapsing symptoms post-herpes simplex encephalitis (HSE) and to compare the clinical and immunologic features of the teenage and adult group with those of young children. Methods: Prospective observational study of patients diagnosed between June 2013 and February 2015. Immunologic techniques have been reported previously. Results: Among the teenage and adult group (8 patients, median age 40 years, range 13-69; 5 male), 3 had an acute symptom presentation suggesting a viral relapse, and 5 a presentation contiguous with HSE suggesting a recrudescence of previous deficits. Seven patients developed severe psychiatric/behavioral symptoms disrupting all social interactions, and one refractory status epilepticus. Blepharospasm occurred in one patient. Five patients had CSF antibodies against NMDA receptor (NMDAR) and 3 against unknown neuronal cell surface proteins. In 5/6 patients, the brain MRI showed new areas of contrast enhancement that decreased after immunotherapy and clinical improvement. Immunotherapy was useful in 7/7 patients, sometimes with impressive recoveries, returning to their baseline HSE residual deficits. Compared with the 6 younger children (median age 13 months, range 6-20, all with NMDAR antibodies), the teenagers and adults were less likely to develop choreoathetosis (0/8 vs 6/6, p < 0.01) and decreased level of consciousness (2/8 vs 6/6, p < 0.01) and had longer delays in diagnosis and treatment (interval relapse/antibody testing 85 days, range 17-296, vs 4 days, range 0-33, p = 0.037). Conclusion: In teenagers and adults, the immune-mediated relapsing syndrome post-HSE is different from that known in young children as choreoathetosis post-HSE and is underrecognized. Prompt diagnosis is important because immunotherapy can be highly effective.
    No preview · Article · Oct 2015 · Neurology
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    ABSTRACT: OBJECTIVE: To report 14 patients with immune-mediated relapsing symptoms post-herpes simplex encephalitis (HSE) and to compare the clinical and immunologic features of the teenage and adult group with those of young children. METHODS: Prospective observational study of patients diagnosed between June 2013 and February 2015. Immunologic techniques have been reported previously. RESULTS: Among the teenage and adult group (8 patients, median age 40 years, range 13-69; 5 male), 3 had an acute symptom presentation suggesting a viral relapse, and 5 a presentation contiguous with HSE suggesting a recrudescence of previous deficits. Seven patients developed severe psychiatric/behavioral symptoms disrupting all social interactions, and one refractory status epilepticus. Blepharospasm occurred in one patient. Five patients had CSF antibodies against NMDA receptor (NMDAR) and 3 against unknown neuronal cell surface proteins. In 5/6 patients, the brain MRI showed new areas of contrast enhancement that decreased after immunotherapy and clinical improvement. Immunotherapy was useful in 7/7 patients, sometimes with impressive recoveries, returning to their baseline HSE residual deficits. Compared with the 6 younger children (median age 13 months, range 6-20, all with NMDAR antibodies), the teenagers and adults were less likely to develop choreoathetosis (0/8 vs 6/6, p < 0.01) and decreased level of consciousness (2/8 vs 6/6, p < 0.01) and had longer delays in diagnosis and treatment (interval relapse/antibody testing 85 days, range 17-296, vs 4 days, range 0-33, p = 0.037). CONCLUSION: In teenagers and adults, the immune-mediated relapsing syndrome post-HSE is different from that known in young children as choreoathetosis post-HSE and is underrecognized. Prompt diagnosis is important because immunotherapy can be highly effective.
    No preview · Article · Oct 2015 · Neurology

  • No preview · Conference Paper · Oct 2015
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    ABSTRACT: Background: Primary central nervous system lymphomas may present as diffuse, nonenhancing infiltrative lesions. This rare variant is termed lymphomatosis cerebri (LC). We did a systematic review and analysis of the literature, adding our own cases, to better characterize LC in order to improve early diagnosis and treatment. Methods: PubMed, ISI Web of Knowledge, and hospital databases were reviewed. Information was extracted regarding demographic, clinical, histological, cerebrospinal fluid (CSF), neuroimaging, and treatment variables. The impact of single parameters on overall survival (OS) was determined by applying univariate and multivariate analyses. Results: Forty-two patients were included (median age: 58 y; range: 28-80 y). At consultation, 52% of patients had a poor KPS. The most common presenting symptom was cognitive decline (59.5%). Imaging studies showed supratentorial and infratentorial infiltration in 55% of patients and bilateral hemispheric involvement in 95%. CSF pleocytosis was present in 51.5% of the patients. Median time to diagnosis was 4.5 (range: 1-30) months, and the diagnosis was not established until autopsy for 33% of patients. The median OS was 2.95 (range: 0.33-56) months; however, those patients who received methotrexate had a median OS of 13.8 (range: 0.7-56) months. Analysis identified KPS ≥ 70 (HR: 0.32; 95% CI: 0.114-0.894; P = .03) and treatment with methotrexate (HR: 0.19; 95% CI: 0.041-0.886; P = .034) as independent favorable prognostic factors, whereas T-cell lymphoma was independently related with a worse outcome (HR: 6.62; 95% CI: 1.317-33.316; P = .022). Conclusions: LC is a misdiagnosed entity associated with considerable diagnostic delay. MRI evidence of bilateral hemispheric involvement and CSF pleocytosis should be alerts for this diagnosis. Treatment with methotrexate-based chemotherapy must be considered, especially for patients with good KPS.
    No preview · Article · Sep 2015 · Neuro-Oncology
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    ABSTRACT: Since a decline in the ovary function might impact the reproductive potential in women with multiple sclerosis (MS), we investigated the pituitary-ovary axis and ovarian reserve, including anti-Müllerian hormone (AMH) levels and ultrasound imaging of the ovaries, of 25 relapsing-remitting MS patients and 25 age-matched healthy controls. Mean levels of pituitary-gonadal hormones and age-adjusted parameters of ovarian reserve markers were not significantly different between both groups. Patients with higher disease activity (annualized relapse rate >0.5; n=9) had significantly lower AMH levels, total antral follicle count and ovarian volume, than those with lower disease activity. The finding of poorer ovarian reserve associated with higher disease activity should be taken into consideration since it may negatively impact the reproductive prognosis.
    Full-text · Article · Sep 2015 · Multiple Sclerosis
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    Full-text · Article · Aug 2015

  • No preview · Article · Jul 2015 · Scandinavian journal of rheumatology
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    ABSTRACT: The management of primary CNS lymphoma is one of the most controversial topics in neuro-oncology because of the complexity of the disease and the very few controlled studies available. In 2013, the European Association of Neuro-Oncology created a multidisciplinary task force to establish evidence-based guidelines for immunocompetent adults with primary CNS lymphoma. In this Review, we present these guidelines, which provide consensus considerations and recommendations for diagnosis, assessment, staging, and treatment of primary CNS lymphoma. Specifically, we address aspects of care related to surgery, systemic and intrathecal chemotherapy, intensive chemotherapy with autologous stem-cell transplantation, radiotherapy, intraocular manifestations, and management of elderly patients. The guidelines should aid clinicians in their daily practice and decision making, and serve as a basis for future investigations in neuro-oncology. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Full-text · Article · Jul 2015 · The Lancet Oncology
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    ABSTRACT: Little is known of glutamic acid decarboxylase antibodies (GAD-abs) in the paraneoplastic context. Clinical recognition of such cases will lead to prompt tumor diagnosis and appropriate treatment. To report the clinical and immunological features of patients with paraneoplastic neurological syndromes (PNS) and GAD-abs. Retrospective case series study and immunological investigations conducted in February 2014 in a center for autoimmune neurological disorders. Fifteen cases with GAD65-abs evaluated between 1995 and 2013 who fulfilled criteria of definite or possible PNS without concomitant onconeural antibodies were included in this study. Analysis of the clinical records of 15 patients and review of 19 previously reported cases. Indirect immunofluorescence with rat hippocampal neuronal cultures and cell-based assays with known neuronal cell-surface antigens were used. One hundred six patients with GAD65-abs and no cancer served as control individuals. Eight of the 15 patients with cancer presented as classic paraneoplastic syndromes (5 limbic encephalitis, 1 paraneoplastic encephalomyelitis, 1 paraneoplastic cerebellar degeneration, and 1 opsoclonus-myoclonus syndrome). When compared with the 106 non-PNS cases, those with PNS were older (median age, 60 years vs 48 years; P = .03), more frequently male (60% vs 13%; P < .001), and had more often coexisting neuronal cell-surface antibodies, mainly against γ-aminobutyric acid receptors (53% vs 11%; P < .001). The tumors more frequently involved were lung (n = 6) and thymic neoplasms (n = 4). The risk for an underlying tumor was higher if the presentation was a classic PNS, if it was different from stiff-person syndrome or cerebellar ataxia (odds ratio, 10.5; 95% CI, 3.2-34.5), or if the patient had coexisting neuronal cell-surface antibodies (odds ratio, 6.8; 95% CI, 1.1-40.5). Compared with the current series, the 19 previously reported cases had more frequent stiff-person syndrome (74% vs 13%; P = .001) and better responses to treatment (79% vs 27%; P = .005). Predictors of improvement in the 34 patients (current and previously reported) included presentation with stiff-person syndrome and the presence of a thymic tumor. Patients with GAD-abs must be screened for an underlying cancer if they have clinical presentations different from those typically associated with this autoimmunity or develop classic PNS. The risk for cancer increases with age, male sex, and the presence of coexisting neuronal cell-surface antibodies.
    No preview · Article · Jun 2015
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    ABSTRACT: We report the clinical features, comorbidities, and outcome of 22 newly identified patients with antibodies to the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR). This was a retrospective review of patients diagnosed between May 2009 and March 2014. Immunologic techniques have been reported previously. Patients' median age was 62 years (range 23-81; 14 female). Four syndromes were identified: 12 (55%) patients presented with distinctive limbic encephalitis (LE), 8 (36%) with limbic dysfunction along with multifocal/diffuse encephalopathy, one with LE preceded by motor deficits, and one with psychosis with bipolar features. Fourteen patients (64%) had a tumor demonstrated pathologically (5 lung, 4 thymoma, 2 breast, 2 ovarian teratoma) or radiologically (1 lung). Additional antibodies occurred in 7 patients (3 onconeuronal, 1 tumor-related, 2 cell surface, and 1 tumor-related and cell surface), all with neurologic symptoms or tumor reflecting the concurrent autoimmunity. Treatment and outcome were available from 21 patients (median follow-up 72 weeks, range 5-266): 5 had good response to immunotherapy and tumor therapy, 10 partial response, and 6 did not improve. Eventually 5 patients died; all had a tumor or additional paraneoplastic symptoms related to onconeuronal antibodies. Coexistence of onconeuronal antibodies predicted a poor outcome (p = 0.009). Anti-AMPAR encephalitis usually manifests as LE, can present with other symptoms or psychosis, and is paraneoplastic in 64% of cases. Complete and impressive neurologic improvement can occur, but most patients have partial recovery. Screening for a tumor and onconeuronal antibodies is important because their detection influences outcome. © 2015 American Academy of Neurology.
    No preview · Article · May 2015 · Neurology
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    ABSTRACT: Walking limitation is a key component of disability in patients with multiple sclerosis (MS), but the information on daily walking activity and disability over time is limited. To determine, (1) the agreement between the standard measurements of MS-related disability [expanded disability status scale (EDSS), functional systems (FS) and ambulation index (AI)] obtained by conventional and remote evaluation using a multimedia platform; (2) the usefulness of monitoring 6-min walk test (6MWT) and average daily walking activity (aDWA) to better characterize patients disability. Twenty-five patients (EDSS score 1.0–6.5) were evaluated every 3 months for the first year, and aDWA repeated at year 2. Remote visits included the recording of a video with self-performed neurological examination and specific multimedia questionnaires. aDWA was measured by a triaxial accelerometer. All but two patients completed the study. Modest agreement between conventional and multimedia EDSS was found for EDSS ≤ 4.0 (kappa = 0.2) and good for EDSS ≥ 4.5 (kappa = 0.6). For the overall sample, pyramidal, cerebellar and brainstem FS showed the greatest agreement (kappa = 0.7). SR-AI showed a modest agreement for EDSS ≤ 4.0 and good for EDSS ≥ 4.5 (kappa = 0.3 and 0.6, respectively). There was a strong correlation between conventional and 6MWT measured by accelerometer (r = 0.76). The aDWA correlated strongly with the EDSS (r = −0.86) and a cut-off point of 3279.3 steps/day discriminated patients with ambulatory impairment. There was a significant decline in aDWA over 2 years in patients with ambulatory impairment that were not observed by standard measurements of disability. MS clinical monitoring by telemedicine is feasible, but the observed lower agreement in less disabled patients emphasizes the need to optimize the assessment methodology. Accelerometers capture changes that may indicate deterioration over time.
    Full-text · Article · May 2015 · Journal of Neurology

  • No preview · Article · May 2015 · Clinical neurophysiology: official journal of the International Federation of Clinical Neurophysiology

  • No preview · Article · May 2015 · European Journal of Paediatric Neurology
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    ABSTRACT: At least 13 different disease entities affecting the central nervous system, peripheral nervous system and connective tissue of the skin or kidneys are associated with immunoglobulin G4 (IgG4) immune reactivity. IgG4 has always been considered a benign, non-inflammatory subclass of IgG, in contrast to the well-known complement-activating pro-inflammatory IgG1 subclass. A comprehensive review of these IgG4 autoimmune disorders reveals striking similarities in epitope binding and human leukocyte antigen (HLA) associations. Mechanical interference of extracellular ligand-receptor interactions by the associated IgG4 antibodies seems to be the common/converging disease mechanism in these disorders. © 2015 EAN.
    Full-text · Article · May 2015 · European Journal of Neurology

  • No preview · Article · Apr 2015 · The Lancet

Publication Stats

16k Citations
2,321.88 Total Impact Points

Institutions

  • 2015
    • Hospital de la Santa Creu i Sant Pau
      Barcino, Catalonia, Spain
  • 2001-2015
    • IDIBAPS August Pi i Sunyer Biomedical Research Institute
      Barcino, Catalonia, Spain
    • Autonomous University of Barcelona
      Cerdanyola del Vallès, Catalonia, Spain
  • 1991-2015
    • University of Barcelona
      • Department of Medicine
      Barcino, Catalonia, Spain
  • 1988-2015
    • Hospital Clínic de Barcelona
      • • Servicio de Neurología
      • • Servicio de Oncología Radioterápica
      Barcino, Catalonia, Spain
  • 1987-2015
    • Institut Marqués, Spain, Barcelona
      Barcino, Catalonia, Spain
  • 2013
    • Catalan Institution for Research and Advanced Studies
      Barcino, Catalonia, Spain
    • University of Pennsylvania
      • Department of Neurology
      Philadelphia, Pennsylvania, United States
  • 2012
    • Hospital Universitari de Bellvitge
      l'Hospitalet de Llobregat, Catalonia, Spain
  • 2011
    • University of Padova
      • Department of Neurosciences
      Padova, Veneto, Italy
    • Hospital do Meixoeiro
      Vigo, Galicia, Spain
  • 1992-2009
    • Hospital Clínico, Maracaibo
      Maracaibo, Zulia, Venezuela
  • 2006
    • University Hospital Donostia
      San Sebastián, Basque Country, Spain
  • 1997
    • Nartex Barcelona
      Barcino, Catalonia, Spain
  • 1985-1997
    • Memorial Sloan-Kettering Cancer Center
      • Department of Neurology
      New York City, NY, United States