Syndrome of Transient Headache and Neurologic Deficits with Cerebrospinal Fluid Lymphocytosis (HaNDL): HHV-7 Finding in Cerebrospinal Fluid Challenges Diagnostic Criteria.

The syndrome of transient headache and neurologic deficits with cerebrospinal fluid lymphocytosis (HaNDL) is a rare, self-limiting condition with severe headaches combined with neurological symptoms. However, evidence-based recommendations on diagnostics and treatments are unavailable due to the condition's rarity and unknown pathophysiology. A young man experiencing severe headache attacks fulfilled the HaNDL diagnostic criteria according to the third edition of the International Classification of Headache Disorders (ICHD-3).

Can fatigue predict the worsening of multiple sclerosis one year later? An explorative study with participants referred to assess their ability to work.

Background: Multiple sclerosis (MS) is an inflammatory and degenerative disease of the central nervous system and is triggered by several environmental factors in genetically predisposed people.

Objectives: To explore which evaluation battery items used for evaluation of work capacity at baseline can best predict MS progression at 1 year follow-up.

Methods: In this prospective single-centre study, participants with MS were recruited consecutively when visiting a neurologist for referral for the determination work capacity status at the Disability and Working Capacity Assessment Office.

Adult-Onset Leukoencephalopathy With Axonal Spheroids and Pigmented Glia: Review of Clinical Manifestations as Foundations for Therapeutic Development.

A comprehensive review of published literature was conducted to elucidate the genetics, neuropathology, imaging findings, prevalence, clinical course, diagnosis/clinical evaluation, potential biomarkers, and current and proposed treatments for adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), a rare, debilitating, and life-threatening neurodegenerative disorder for which disease-modifying therapies are not currently available. Details on potential efficacy endpoints for future interventional clinical trials in patients with ALSP and data related to the burden of the disease on patients and caregivers were also reviewed. The information in this position paper lays a foundation to establish an effective clinical rationale and address the clinical gaps for creation of a robust strategy to develop therapeutic agents for ALSP, as well as design future clinical trials, that have clinically meaningful and convergent endpoints.

Cerebrospinal fluid markers in incident pediatric-onset multiple sclerosis: a nationwide study.

To investigate whether cerebrospinal fluid (CSF) markers differ between pediatric-onset multiple sclerosis (PoMS, onset < 18 years) and adult-onset (AoMS), and whether these markers are associated with clinical outcomes among PoMS. Prospective nationwide registry study of incident MS, including persons with a CSF sample < 3 years post-MS onset. We compared CSF oligoclonal band (OCB) status, immunoglobulin G (IgG) index levels, and mononuclear cell count between PoMS and AoMS.

Cerebrospinal fluid oligoclonal immunoglobulin gamma bands and long-term disability progression in multiple sclerosis: a retrospective cohort study.

Multiple sclerosis (MS) patients with immunoglobulin gamma (IgG) oligoclonal bands (OCB) in the cerebrospinal fluid (CSF) have different genetic backgrounds and brain MRI features compared to those without. In this study, we aimed to determine whether CSF-OCB status is associated with long-term disability outcomes. We used Swedish MS register data on clinically definite MS patients with known OCB status.

Microglial replacement therapy: a potential therapeutic strategy for incurable CSF1R-related leukoencephalopathy.

CSF1R-related leukoencephalopathy is an adult-onset leukoencephalopathy with axonal spheroids and pigmented glia caused by colony stimulating factor 1 receptor (CSF1R) gene mutations. The disease has a global distribution and currently has no cure. Individuals with CSF1R-related leukoencephalopathy variably present clinical symptoms including cognitive impairment, progressive neuropsychiatric and motor symptoms.

Accurate classification of secondary progression in multiple sclerosis using a decision tree.

Background: The absence of reliable imaging or biological markers of phenotype transition in multiple sclerosis (MS) makes assignment of current phenotype status difficult.

Objective: The authors sought to determine whether clinical information can be used to accurately assign current disease phenotypes.

Methods: Data from the clinical visits of 14,387 MS patients in Sweden were collected.

Plasma neurofilament light chain concentration is increased in anorexia nervosa.

Anorexia nervosa (AN) is a severe psychiatric disorder with high mortality and, to a large extent, unknown pathophysiology. Structural brain differences, such as global or focal reductions in grey or white matter volumes, as well as enlargement of the sulci and the ventricles, have repeatedly been observed in individuals with AN. However, many of the documented aberrances normalize with weight recovery, even though some studies show enduring changes.

Different Interferon Beta Preparations Induce the Same Qualitative Immune Response in Human Skin.

Interferon beta (IFNβ) is used as a first-line treatment for multiple sclerosis (MS) and is injected intramuscularly or subcutaneously (s.c.).

Cognitive function predicts work disability among multiple sclerosis patients.

Background: In multiple sclerosis various aspects of cognitive function can be detrimentally affected. More than that, patients´ employment and social functioning is likely to be impacted.

Objective: To determine whether work disability among multiple sclerosis patients could be predicted by the symbol digit modalities test.

Similar familial risk in multiple sclerosis subgroups.

Background: A subgroup of patients diagnosed with multiple sclerosis (MS) present with no oligoclonal bands (OCB) in the cerebrospinal fluid (CSF). Several studies report different clinical characteristics and genetic associations between the two groups.

Objective: To investigate whether the OCB negative subgroup has a distinct etiology from band positive MS.

Guidelines for the use of magnetic resonance imaging in diagnosing and monitoring the treatment of multiple sclerosis: recommendations of the Swedish Multiple Sclerosis Association and the Swedish Neuroradiological Society.

Multiple sclerosis (MS) is associated with inflammatory lesions in the brain and spinal cord. The detection of such inflammatory lesions using magnetic resonance imaging (MRI) is important in the consideration of the diagnosis and differential diagnoses of MS, as well as in the monitoring of disease activity and predicting treatment efficacy. Although there is strong evidence supporting the use of MRI for both the diagnosis and monitoring of disease activity, there is a lack of evidence regarding which MRI protocols to use, the frequency of examinations, and in what clinical situations to consider MRI examination.

Hereditary diffuse leukoencephalopathy with spheroids - a volumetric and radiological comparison with multiple sclerosis patients and healthy controls.

Background And Purpose: Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is an autosomal dominant disorder caused by colony-stimulating factor 1 receptor (CSF1R) gene mutations, resulting in demyelination and axonal degeneration with spheroids. The clinical expression is variable, including behavioral changes, cognitive impairment, motor symptoms and parkinsonism. Magnetic resonance imaging (MRI) reveals white matter (WM) changes and atrophy.

Reduced cerebrospinal fluid concentrations of oxysterols in response to natalizumab treatment of relapsing remitting multiple sclerosis.

Background: Natalizumab therapy reduces inflammation and degeneration of the CNS in relapsing-remitting multiple sclerosis (RRMS). In cerebrospinal fluid (CSF) the concentration of 24S-hydroxycholesterol (24OHC) reflect neurodegeneration, whereas 27-hydroxycholesterol (27OHC) is dependent on the integrity of the blood-brain barrier (BBB).

Objective: To measure the impact from natalizumab treatment on 24OHC and 27OHC concentrations in serum and CSF of RRMS.

Hereditary diffuse leukoencephalopathy with spheroids with phenotype of primary progressive multiple sclerosis.

Background And Purpose: Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is a devastating, hereditary white matter (WM) disorder with heterogeneous neuropsychiatric features. Colony stimulating factor 1 receptor (CSF1R) mutations were looked for in primary progressive multiple sclerosis (PPMS) patients and the clinical features of a family with a novel CSF1R mutation are reported.

Methods: CSF1R exons 12-22 in a cohort of 220 PPMS patients from the Swedish and Norwegian national multiple sclerosis registries were sequenced.

Multiple sclerosis patients lacking oligoclonal bands in the cerebrospinal fluid have less global and regional brain atrophy.

To investigate whether multiple sclerosis (MS) patients with and without cerebrospinal fluid (CSF) oligoclonal immunoglobulin G bands (OCB) differ in brain atrophy. Twenty-eight OCB-negative and thirty-five OCB-positive patients were included. Larger volumes of total CSF and white matter (WM) lesions; smaller gray matter (GM) volume in the basal ganglia, diencephalon, cerebellum, and hippocampus; and smaller WM volume in corpus callosum, periventricular-deep WM, brainstem, and cerebellum, were observed in OCB-positives.

Interferon beta treatment of multiple sclerosis increases serum interleukin-7.

Background: Interleukin-7 (IL-7) is a non-redundant cytokine for T-cell development and survival. The IL-7 signaling pathway has been genetically and functionally associated with several autoimmune diseases including multiple sclerosis (MS).

Objective: The objective of this paper is to elucidate the effect of the widely used immunomodulatory MS therapy interferon beta (IFNβ) on IL-7 homeostasis.

Impact of cerebrospinal-fluid oligoclonal immunoglobulin bands and HLA-DRB1 risk alleles on brain magnetic-resonance-imaging lesion load in Swedish multiple sclerosis patients.

Approximately 95% of Nordic multiple sclerosis (MS) patients display oligoclonal immunoglobulin G bands (OCB) in the cerebrospinal fluid. From a cohort of 2094 MS patients we retrieved well-characterized data from 40 OCB-negative and 60 OCB-positive patients, in an effort to determine whether lesion load on brain magnetic resonance imaging is affected by OCB status and carriage of HLA-DRB1*15 or HLA-DRB1*04. Positivity for OCB did not increase the risk of belonging to higher-lesion-load groups; nor did carrying HLA-DRB1*15 or HLA-DRB1*04.

Functional neuroimaging in multiple sclerosis with radiolabelled glia markers: preliminary comparative PET studies with [11C]vinpocetine and [11C]PK11195 in patients.

With the purpose of demonstrating the use of positron emission tomography (PET) and radiolabelled glia markers to indicate regional cerebral damage, we measured with PET in four young multiplex sclerosis (MS) patients in two consecutive measurements the global and regional brain uptake as well as regional distribution and binding potential (BP) of [(11)C]vinpocetine and [(11)C]PK11195. Both ligands showed increased uptake and BP in the regions of local brain damage. However, regional BP values for [(11)C]vinpocetine were markedly higher than those for [(11)C]PK11195.

Increased soluble 4-1BB ligand (4-1BBL) levels in peripheral blood of patients with multiple sclerosis.

4-1BB ligand (4-1BBL; CD137L) is a member of the tumour necrosis factor superfamily expressed primarily on antigen presenting cells such as B cells, macrophages and dendritic cells. Its engagement with the receptor 4-1BB (CD137) has been shown to promote T-cell activation and regulate proliferation and survival of T cells. The role of the costimulatory molecule in multiple sclerosis (MS) remains unclear.

Plasma cerebrosterol and magnetic resonance imaging measures in multiple sclerosis.

Objectives: The concentration in plasma of the brain-specific cholesterol metabolite cerebrosterol has been proposed as a biomarker of neurodegeneration in multiple sclerosis (MS) and other neurological diseases. It is unknown, however, which pathophysiological process in MS best accounts for variations in plasma cerebrosterol.

Patients And Methods: In this study, we related plasma cerebrosterol concentrations in 46 MS patients - 27 with a relapsing-remitting (RR) disease course and 19 with a primary progressive (PP) course - to three conventional magnetic resonance imaging measures: on T(1)-weighted brain scans, volume of gadolinium-enhanced lesions (a marker of active inflammation) and hypointense lesions (a marker of edema or axonal loss) and on T(2)-weighted scans, volume of hyperintense lesions (a marker of disease extent).

Increased levels of APRIL (a proliferation-inducing ligand) mRNA in multiple sclerosis.

B cells play an indispensable, yet indeterminate, role in the pathogenesis of multiple sclerosis (MS). We measured mRNA of APRIL-a promotor of B-cell survival-in peripheral blood and quantified protein levels in plasma and cerebrospinal fluid in MS patients and controls. APRIL mRNA levels in monocytes and T cells were significantly higher in MS patients than in controls.