Reference programme: Diagnosis and treatment of headache disorders and facial pain. Danish Headache Society, 2nd Edition, 2012

Headache and facial pain are among the most common, disabling and costly disorders in Europe. Correct diagnosis and treatment is important for achieving a high quality of care. As a national organisation whose role is to educate and advocate for the needs of patients with primary headaches, the Danish Headache Society has set up a task force to develop a set of guidelines for the diagnosis, organisation and treatment of the most common types of headaches and for trigeminal neuralgia in Denmark. The guideline was published in Danish in 2010 and has been a great success. The Danish Headache Society decided to translate and publish our guideline in English to stimulate the discussion on optimal organisation and treatment of headache disorders and to encourage other national headache authorities to produce their own guidelines. The recommendations regarding the most common primary headaches and trigeminal neuralgia are largely in accordance with the European guidelines produced by the European Federation of Neurological Societies. The guideline provides a practical tool for use in daily clinical practice for primary care physicians, neurologists with a common interest in headache, as well as other health-care professionals treating headache patients. The guideline first describes how to examine and diagnose the headache patient and how headache treatment is organised in Denmark. This description is followed by individual sections on the characteristics, diagnosis, differential diagnosis and treatment of each of the major headache disorders and trigeminal neuralgia. The guideline includes many tables to facilitate a quick overview. Finally, the particular problems regarding headache in children and headache in relation to female hormones and pregnancy are described

Microfibrillar-associated protein 4 as a potential marker of acute relapse in inflammatory demyelinating diseases of the central nervous system: Pathological and clinical aspects

Background: Microfibrillar-associated protein 4 (MFAP4) is an extracellular matrix protein not previously described in the human central nervous system (CNS). Objectives: We determined MFAP4 CNS expression and measured cerebrospinal fluid (CSF) and serum levels. Methods: Tissue was sampled at autopsy from patients with acute multiple sclerosis (MS) (n = 3), progressive MS (n = 3), neuromyelitis optica spectrum disorder (NMOSD) (n = 2), and controls (n = 9), including 6 healthy controls (HC). MFAP4 levels were measured in 152 patients: 49 MS, 62 NMOSD, 22 myelin oligodendrocyte glycoprotein-associated disease (MOGAD), and 19 isolated optic neuritis (ION). Results: MFAP4 localized to meninges and vascular/perivascular spaces, intense in the optic nerve. At sites of active inflammation, MFAP4 reactivity was reduced in NMOSD and acute MS and less in progressive MS. CSF MFAP4 levels were reduced during relapse and at the onset of diseases (mean U/mL: MS 14.3, MOGAD 9.7, and ION 14.6 relative to HC 17.9. (p = 0.013, p = 0.000, and p = 0.019, respectively). Patients with acute ON (n = 68) had reduced CSF MFAP4 (mean U/mL: 14.5, p = 0.006). CSF MFAP4 levels correlated negatively with relapse severity (rho = -0.41, p = 0.017). Conclusion: MFAP4 immunoreactivity was reduced at sites of active inflammation. CSF levels of MFAP4 were reduced following relapse and may reflect disease activity

Modulatory and catalytic modes of ATP binding by the calcium pump

We present crystal structures of the calcium-free E2 state of the sarcoplasmic reticulum Ca(2+)-ATPase, stabilized by the inhibitor thapsigargin and the ATP analog AMPPCP. The structures allow us to describe the ATP binding site in a modulatory mode uncoupled from the Asp351 phosphorylation site. The Glu439 side chain interacts with AMPPCP via an Mg(2+) ion in accordance with previous Fe(2+)-cleavage studies implicating this residue in the ATPase cycle and in magnesium binding. Functional data on Ca(2+) mediated activation indicate that the crystallized state represents an initial stage of ATP modulated deprotonation of E2, preceding the binding of Ca(2+) ions in the membrane from the cytoplasmic side. We propose a mechanism of Ca(2+) activation of phosphorylation leading directly from the compact E2-ATP form to the Ca(2)E1-ATP state. In addition, a role of Glu439 in ATP modulation of other steps of the functional cycle is suggested

sj-docx-1-msj-10.1177_13524585231200720 – Supplemental material for Microfibrillar-associated protein 4 as a potential marker of acute relapse in inflammatory demyelinating diseases of the central nervous system: Pathological and clinical aspects

Supplemental material, sj-docx-1-msj-10.1177_13524585231200720 for Microfibrillar-associated protein 4 as a potential marker of acute relapse in inflammatory demyelinating diseases of the central nervous system: Pathological and clinical aspects by Sara Samadzadeh, Mads Nikolaj Olesen, Martin Wirenfeldt, Sören Möller, Tatsuro Misu, Kerstin Soelberg, Jette Lautrup Frederiksen, Steffen Heegaard, Sara Mariotto, Kazuo Fujihara, Klemens Ruprecht, Thomas Levin Andersen, Romain Marignier, Søren Thue Lillevang, Eoin P Flanagan, Sean J Pittock, Ho Jin Kim, Jeffrey L Bennett, Friedemann Paul, Grith Lykke Sorensen, Brian G Weinshenker, Hans Lassmann and Nasrin Asgari in Multiple Sclerosis Journal</p

Allogeneic hematopoietic cell transplantation with non-myeloablative conditioning for patients with hematologic malignancies improved outcomes over two decades

We have used a non-myeloablative conditioning regimen for allogeneic hematopoietic cell transplantation for the past 20 years. During that period, changes in clinical practice have been aimed at reducing morbidity and mortality from infections, organ toxicity, and graft-versus-host disease. We hypothesized that improvements in clinical practice led to better transplantation outcomes over time. From 1997-2017, 1,720 patients with hematologic malignancies received low-dose total body irradiation +/- fludarabine or clofarabine before transplantation from HLAmatched sibling or unrelated donors, followed by mycophenolate mofetil and a calcineurin inhibitor +/- sirolimus. We compared outcomes in three cohorts by year of transplantation: 1997-2003 (n=562), 2004-2009 (n =594), and 2010-2017 (n=564). The proportion of patients >= 60 years old increased from 27% in 1997-2003 to 56% in 2010-2017, and with scores from the Hematopoietic Cell Transplantation Comorbidity Index of >= 3 increased from 25% in 1997-2003 to 45% in 2010-2017. Use of unrelated donors increased from 34% in 1997-2003 to 65% in 2010-2017. When outcomes from 2004-2009 and 2010-2017 were compared to 1997-2003, improvements were noted in overall survival (P=0.0001 for 2004-2009 and P <= 0.0001 for 2010-2017), progression-free survival (P=0.002 for 2004-2009 and P<0.0001 for 2010-2017), non-relapse mortality (P<0.0001 for 20042009 and P<0.0001 for 2010-2017), and in rates of grades 2-4 acute and chronic graft-versus-host disease. For patients with hematologic malignancies who underwent transplantation with non-myeloablative conditioning, outcomes have improved during the past two decades