Expanding the MOG phenotype: Brainstem encephalitis with punctate and curvilinear enhancement
Myelin oligodendrocyte glycoprotein antibody (MOG-Ab)-associated demyelination has been associated with a range of clinical phenotypes, including acute disseminated encephalomyelitis (ADEM), ADEM followed by recurrent optic neuritis, aquaporin 4–negative neuromyelitis optica spectrum disorder, and less commonly, brainstem encephalitis.1 In contrast, chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is a clinical, radiologic, and pathologic diagnosis without an associated antibody.2,3 There have been few reported cases of pediatric CLIPPERS,4 and most have not cle...
Source: Neurology Neuroimmunology and Neuroinflammation - September 13, 2019 Category: Neurology Authors: Matesanz, S., Kotch, C., Perrone, C., Waanders, A. J., Hill, B., Narula, S. Tags: Encephalitis, All Pediatric, All Demyelinating disease (CNS) Clinical/Scientific Notes Source Type: research

Lymphocyte counts and infection rates: Long-term fingolimod treatment in primary progressive MS
Conclusions In patients with PPMS, long-term treatment with fingolimod 0.5 mg/d for up to 5 years led to an expected decrease of approximately 70% in mean ALC and did not appear to correlate with increased risk of infection. Classification of evidence Because this is a secondary analysis, this study provides Class II evidence that long-term PPMS treatment with fingolimod decreased mean ALC by approximately 70%, but did not significantly increase infection risk. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - September 11, 2019 Category: Neurology Authors: Fox, E. J., Lublin, F. D., Wolinsky, J. S., Cohen, J. A., Williams, I. M., Meng, X., Ziehn, M., Kolodny, S., Cree, B. A. C. Tags: All Infections, Clinical trials Randomized controlled (CONSORT agreement), Multiple sclerosis Article Source Type: research

Neurochondrin neurological autoimmunity
Conclusion In our series, neurochondrin autoimmunity was usually accompanied by a nonparaneoplastic rapidly progressive rhombencephalitis with poor neurologic outcomes. Other phenotypes and occasional paraneoplastic causes may occur. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - September 11, 2019 Category: Neurology Authors: Shelly, S., Kryzer, T. J., Komorowski, L., Miske, R., Anderson, M. D., Flanagan, E. P., Hinson, S. R., Lennon, V. A., Pittock, S. J., McKeon, A. Tags: Autoimmune diseases, All Movement Disorders, Gait disorders/ataxia Article Source Type: research

Toll-like receptor 3 deficiency in autoimmune encephalitis post-herpes simplex encephalitis
The Toll-like receptor 3 (TLR3) pathway is a key component of the innate immunity that prevents replication of viruses in the CNS. Inborn errors of this pathway (TLR3-pathway deficiency), which includes defects in the genes TLR3, UNC93B1, TRIF, TRAF3, TBK1 and IRF3, occur in 10% of patients with herpes simplex encephalitis (HSE),1,2 and about 66% of these patients develop relapses of HSE.1 A recent study showed that 27% of patients with HSE develop autoimmune encephalitis (AE) in the weeks or months ensuing the infection.3 It is unknown whether TLR3-pathway deficient patients can also develop AE post-HSE. Here we report a ...
Source: Neurology Neuroimmunology and Neuroinflammation - September 5, 2019 Category: Neurology Authors: Armangue, T., Baucells, B. J., Vlagea, A., Petit-Pedrol, M., Esteve-Sole, A., Deya-Martinez, A., Ruiz-Garcia, R., Juan, M., Perez de Diego, R., Dalmau, J., Alsina, L. Tags: Autoimmune diseases, Encephalitis, Viral infections, Post-infectious, Psychosis Clinical/Scientific Notes Source Type: research

CSF orexin-A levels after rituximab treatment in recent onset narcolepsy type 1
A 28-year-old man with narcolepsy type 1 (NT1) was referred due to excessive daytime sleepiness starting 5 months earlier, and 2 months prior to his admission, he had 1 to 3 daily cataplexies related to laughter, anger, and surprise, leading to a loss of muscle tone in the face, neck, and legs. Inquiries with Epworth Sleepiness Scale (ESS) was initially 21 of 24 points. Prior to admission, his medical history was insignificant, and physical examination did not show any neurologic deficits. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - September 4, 2019 Category: Neurology Authors: Wasling, P., Malmeström, C., Blennow, K. Tags: Autoimmune diseases, Narcolepsy Clinical/Scientific Notes Source Type: research

CNS-disseminated Angiostrongylus cantonensis mimicking atypical demyelinating disease
A healthy 44-year-old woman developed malaise and severe headache shortly after returning from vacation in Hawaii. As initial symptoms cleared after 24 hours, over the subsequent days, she developed paresthesias in her lower extremities (knees to feet), new-onset urinary retention, and midthoracic radicular pain. Brain MRI revealed nonenhancing lesions in the medulla and midbrain, in addition to punctate subcortical frontal lesions (figure). MRI of the cervical spine revealed 2 nonenhancing lesions at C3-C4 and C6-C7 (figure). She was diagnosed with MS and contemplated disease-modifying therapy (DMT). (Source: Neurology Ne...
Source: Neurology Neuroimmunology and Neuroinflammation - September 4, 2019 Category: Neurology Authors: Long, D., Green, K., Derani, T., Decker, N., Pace, R. J., Aburashed, R. Tags: All Immunology, Meningitis, Parasitic infections, All Demyelinating disease (CNS), Transverse myelitis Clinical/Scientific Notes Source Type: research

Late-onset neuromyelitis optica spectrum disorder: The importance of autoantibody serostatus
Objective To describe the clinical features of late-onset (≥50 years) neuromyelitis optica spectrum disorder (LO-NMOSD), to compare the outcome with that of early-onset (EO-NMOSD), and to identify predictors of disability. Methods A retrospective, multicenter study of 238 patients with NMOSD identified by the 2015 criteria. Clinical and immunologic features of patients with LO-NMOSD were compared with those with EO-NMOSD. All patients were evaluated for aquaporin-4 (AQP4-IgG) and myelin oligodendrocyte glycoprotein (MOG-IgG) antibodies. Results Sixty-nine (29%) patients had LO-NMOSD. Demographic features, initial dise...
Source: Neurology Neuroimmunology and Neuroinflammation - August 30, 2019 Category: Neurology Authors: Sepulveda, M., Delgado-Garcia, G., Blanco, Y., Sola-Valls, N., Martinez-Lapiscina, E. H., Armangue, T., Montejo, C., Pulido-Valdeolivas, I., Martinez-Hernandez, E., Arino, H., Escudero, D., Ruiz-Garcia, R., Llufriu, S., Dalmau, J., Graus, F., Saiz, A. Tags: Prognosis, Devic's syndrome Article Source Type: research

Generation of neuroinflammation in human African trypanosomiasis
Human African trypanosomiasis (HAT) is caused by infection due to protozoan parasites of the Trypanosoma genus and is a major fatal disease throughout sub-Saharan Africa. After an early hemolymphatic stage in which the peripheral tissues are infected, the parasites enter the CNS causing a constellation of neurologic features. Although the CNS stage of HAT has been recognized for over a century, the mechanisms generating the neuroinflammatory response are complex and not well understood. Therefore a better understanding of the mechanisms utilized by the parasites to gain access to the CNS compartment is critical to explaini...
Source: Neurology Neuroimmunology and Neuroinflammation - August 29, 2019 Category: Neurology Authors: Rodgers, J., Steiner, I., Kennedy, P. G. E. Tags: Views [amp ] Reviews Source Type: research

Glutamine antagonism attenuates physical and cognitive deficits in a model of MS
Conclusions JHU-083, a well-tolerated, brain penetrable glutamine antagonist, is a promising novel treatment for both the physical and cognitive deficits of MS. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - August 29, 2019 Category: Neurology Authors: Hollinger, K. R., Smith, M. D., Kirby, L. A., Prchalova, E., Alt, J., Rais, R., Calabresi, P. A., Slusher, B. S. Tags: Autoimmune diseases, Memory, Multiple sclerosis Article Source Type: research

Steroid-sparing agents for the treatment of inflammation in complicated neurocysticercosis
Neurocysticercosis (NCC) is a major cause of neurologic disease and epilepsy worldwide. Clinical manifestations of NCC are primarily due to the inflammatory response against degenerating cysts of the Taenia solium tapeworm, which occurs when cysts lose their ability to evade host immune responses. Patients with subarachnoid or severe parenchymal NCC may also develop chronic inflammation requiring long-term immunosuppression.2 (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - August 20, 2019 Category: Neurology Authors: Anand, P., Mukerji, S. S., Thon, J., Gunaratne, S., Cho, T. A., Venna, N. Tags: All Immunology, All Infections, All Clinical Neurology, Parasitic infections, Post-infectious Clinical/Scientific Notes Source Type: research

Anti-pan-neurofascin IgG3 as a marker of fulminant autoimmune neuropathy
Conclusions Our results indicate that anti–pan-NF-associated neuropathy differs from anti–NF-155-associated neuropathy, and epitope and subclass play a major role in the pathogenesis and severity of anti–NF-associated neuropathy and should be determined to correctly classify patients, also in respect to possible differences in therapeutic response. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - August 16, 2019 Category: Neurology Authors: Stengel, H., Vural, A., Brunder, A.-M., Heinius, A., Appeltshauser, L., Fiebig, B., Giese, F., Dresel, C., Papagianni, A., Birklein, F., Weis, J., Huchtemann, T., Schmidt, C., Körtvelyessy, P., Villmann, C., Meinl, E., Sommer, C., Leypoldt, F., Do Tags: Autoimmune diseases, All Clinical Neurology, Guillain-Barre syndrome, Chronic inflammatory demyelinating polyneuropathy Article Source Type: research

Neurofilament light chain levels in MS: At the doorstep of clinical application
In addition to the mysteries and autobiographies that some of you may be packing for a late summer vacation or long weekend, consider including the current issue of N2. Each article has a plot that will leave you on edge, and here, I will introduce some of them. It is well known that the presentation of MS is diverse, with some patients presenting early with very mild disease and others presenting late with extensive damage from silent disease. Until now, the best biomarker of disease activity and treatment effects has been the MRI. However, MRI has several limitations, including availability, cost, interscan variability, ...
Source: Neurology Neuroimmunology and Neuroinflammation - August 16, 2019 Category: Neurology Authors: Dalmau, J. Tags: Editor ' s Corner Source Type: research

Relationship between retinal inner nuclear layer, age, and disease activity in progressive MS
Objective To investigate whether inner nuclear layer (INL) thickness as assessed with optical coherence tomography differs between patients with progressive MS (P-MS) according to age and disease activity. Methods In this retrospective longitudinal analysis, differences in terms of peripapillary retinal nerve fiber layer (pRNFL), ganglion cell layer + inner plexiform layer (GCIPL), INL and T1/T2 lesion volumes (T1LV/T2LV) were assessed between 84 patients with P-MS and 36 sex- and age-matched healthy controls (HCs) and between patients stratified according to age (cut-off: 51 years) and evidence of clinical/MRI activity i...
Source: Neurology Neuroimmunology and Neuroinflammation - August 12, 2019 Category: Neurology Authors: Cellerino, M., Cordano, C., Boffa, G., Bommarito, G., Petracca, M., Sbragia, E., Novi, G., Lapucci, C., Capello, E., Uccelli, A., Inglese, M. Tags: Optic nerve, Retina, Multiple sclerosis Article Source Type: research

HLA and microtubule-associated protein tau H1 haplotype associations in anti-IgLON5 disease
Objectives We investigated the associations with HLA and microtubule-associated protein tau (MAPT) H1 haplotype in anti-IgLON5 disease, a recently identified disorder characterized by gait instability, brainstem dysfunction, and a prominent sleep disorder in association with IgLON5 antibodies and pathologic findings of a novel neuronal-specific tauopathy. Methods We compared the HLA alleles and MAPT H1/H1 genotype of 35 patients with anti-IgLON5 with healthy controls. The on-line server tool NetMHCIIpan 3.1 was used to predict the IgLON5 peptide binding to HLA Class II molecules. Results The HLA-DRB1*10:01-DQB1*05:01 hap...
Source: Neurology Neuroimmunology and Neuroinflammation - August 12, 2019 Category: Neurology Authors: Gaig, C., Ercilla, G., Daura, X., Ezquerra, M., Fernandez-Santiago, R., Palou, E., Sabater, L., Höftberger, R., Heidbreder, A., Högl, B., Iranzo, A., Santamaria, J., Dalmau, J., Graus, F. Tags: Autoimmune diseases, Association studies in genetics Article Source Type: research

Blood neurofilament light chain at the doorstep of clinical application
Multiples sclerosis (MS) is a chronic progressive disorder of the CNS with inflammatory and neurodegenerative pathomechanisms leading to various degrees of neurologic disability. In the past 2 decades, high-efficacy disease-modifying therapies (DMTs) have become available that lead to near-complete suppression of acute disease activity (relapses, lesion formation) in most patients, and only a small number of patients exhibit an aggressive disease course despite adequate use of DMTs. Here, immunoablation followed by stem cell transplantation (SCT) has emerged in recent years as an efficacious approach to stop acute disease ...
Source: Neurology Neuroimmunology and Neuroinflammation - August 9, 2019 Category: Neurology Authors: Leppert, D., Kuhle, J. Tags: Clinical trials Observational study (Cohort, Case control), Class II, Multiple sclerosis Editorial Source Type: research

High serum neurofilament light chain normalizes after hematopoietic stem cell transplantation for MS
Objective To evaluate neurofilament light chain (NfL) levels in serum and CSF of patients with aggressive MS pre- and post-treatment with immunoablation followed by autologous hematopoietic stem cell transplantation (IAHSCT) and examine associations with clinical and MRI outcomes. Methods Paired serum and CSF in addition to MRI and clinical measures were collected on 23 patients with MS at baseline and 1 and 3 years post-IAHSCT. An additional 33 sera and CSF pairs were taken from noninflammatory neurologic controls. NfL levels were quantitated using the Simoa platform (Quanterix). Results Baseline MS NfL levels were sign...
Source: Neurology Neuroimmunology and Neuroinflammation - August 9, 2019 Category: Neurology Authors: Thebault, S., R. Tessier, D., Lee, H., Bowman, M., Bar-Or, A., Arnold, D. L., L. Atkins, H., Tabard-Cossa, V., Freedman, M. S. Tags: Clinical trials Methodology/study design, Clinical trials Observational study (Cohort, Case control), Class II, Multiple sclerosis Article Source Type: research

Increased frequency of anti-Ma2 encephalitis associated with immune checkpoint inhibitors
Conclusions We show a clear association between ICI use and increased diagnosis of Ma2-PNS. Physicians need to be aware that ICIs can trigger Ma2-PNS because clinical presentation can be challenging. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - August 7, 2019 Category: Neurology Authors: Vogrig, A., Fouret, M., Joubert, B., Picard, G., Rogemond, V., Pinto, A.-L., Muniz-Castrillo, S., Roger, M., Raimbourg, J., Dayen, C., Grignou, L., Pallix-Guyot, M., Lannoy, J., Ducray, F., Desestret, V., Psimaras, D., Honnorat, J. Tags: All Immunology, Autoimmune diseases, All Oncology, Paraneoplastic syndrome Article Source Type: research

Cholecalciferol in relapsing-remitting MS: A randomized clinical trial (CHOLINE)
Objective To evaluate the safety and efficacy of cholecalciferol in patients with relapsing-remitting MS (RRMS). Methods In this double-blind, placebo-controlled parallel-group, 2-year study, 181 patients with RRMS were randomized 1:1. Key inclusion criteria were a low serum 25-hydroxy vitamin D (25OHD) concentration (
Source: Neurology Neuroimmunology and Neuroinflammation - August 6, 2019 Category: Neurology Authors: Camu, W., Lehert, P., Pierrot-Deseilligny, C., Hautecoeur, P., Besserve, A., Jean Deleglise, A.-S., Payet, M., Thouvenot, E., Souberbielle, J. C. Tags: Clinical trials Randomized controlled (CONSORT agreement), Multiple sclerosis Article Source Type: research

Peripherally derived macrophages as major phagocytes in MOG encephalomyelitis
An inflammatory demyelinating disease of the CNS with antibody against myelin oligodendrocyte glycoprotein (MOG-IgG) is now accepted as a discrete disease category of MOG encephalomyelitis (MOG-EM).1 Previous case studies described abundant accumulation of phagocytic cells (either Iba1+ and/or CD68+) at the active demyelinating lesions of MOG-EM.2–5 However, both Iba1 and CD68 can be expressed in either the microglia or macrophage.6 Recently, transmembrane protein 119 (TMEM119) has been proposed to be a reliable microglial marker that discriminates resident microglia from blood-derived macrophages in the inflamed hum...
Source: Neurology Neuroimmunology and Neuroinflammation - August 1, 2019 Category: Neurology Authors: Kwon, Y. N., Waters, P. J., Kim, M., Choi, Y. S., Kim, J. W., Sung, J.-J., Park, S.-H., Kim, S.-M. Tags: All Immunology, Autoimmune diseases, All Clinical Neurology, All Demyelinating disease (CNS), Acute disseminated encephalomyelitis Clinical/Scientific Notes Source Type: research

Chronic inflammatory demyelinating polyneuropathy associated with contactin-1 antibodies in a child
A previously healthy 2-year and 9-month old boy was brought to the emergency department for a 6-day history of weakness in the legs and frequent falls, rendering him unable to walk 1 day before admission. He did not have pain, dysphagia, bladder dysfunction, or sensory symptoms. There was no history of trauma, but he developed diarrhea 3 days before symptom onset. Family history was negative for consanguinity or neurologic diseases. At examination, he had bilateral leg weakness requiring substantial aid to walk a few steps and was unable to stand up from the floor. He had absent tendon reflexes in the lower extremities and...
Source: Neurology Neuroimmunology and Neuroinflammation - July 24, 2019 Category: Neurology Authors: Carrera-Garcia, L., Natera-de Benito, D., Lleixa, C., Ortez, C., Colomer, J., Nascimento, A., Saiz, A., Dalmau, J., Querol, L., Armangue, T. Tags: Guillain-Barre syndrome, Chronic inflammatory demyelinating polyneuropathy, All Pediatric, EMG Clinical/Scientific Notes Source Type: research

Intrathecal B-cell accumulation and axonal damage distinguish MRI-based benign from aggressive onset in MS
Conclusion Patients with extreme manifestations of CIS or early MS defined by strict MRI parameters can be best distinguished by combining markers of intrathecal B-cell accumulation and axonal damage. This could stratify individual treatment decisions toward a more personalized immunotherapy. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - July 19, 2019 Category: Neurology Authors: Engel, S., Friedrich, M., Muthuraman, M., Steffen, F., Poplawski, A., Groppa, S., Bittner, S., Zipp, F., Luessi, F. Tags: Multiple sclerosis Article Source Type: research

Lesion activity and chronic demyelination are the major determinants of brain atrophy in MS
Objective To evaluate the combined effect of lesion activity and pathologic processes occurring in both chronically demyelinated lesions and normal-appearing white matter (NAWM) on brain atrophy in MS. Methods Pre- and post-gadolinium T1, fluid attenuation inversion recovery, and diffusion tensor imaging images were acquired from 50 consecutive patients with relapsing-remitting MS (all, but one, on disease-modifying therapy) at baseline and 5 years. Brain atrophy was measured using structural image evaluation, using normalization of atrophy percent brain volume change (PBVC) analysis. Results During follow-up, brain volu...
Source: Neurology Neuroimmunology and Neuroinflammation - July 16, 2019 Category: Neurology Authors: Wang, C., Barnett, M. H., Yiannikas, C., Barton, J., Parratt, J., You, Y., Graham, S. L., Klistorner, A. Tags: MRI, DWI, Multiple sclerosis Article Source Type: research

Hepatitis E virus infections in patients with MS on oral disease-modifying treatment
Conclusion HEV infection is an important differential diagnosis of drug-induced liver injury in pwMS under DMT. Our data do not suggest an increased incidence of acute HEV infections or chronification in pwMS. However, epidemiologic studies in immunomodulatory-treated patients are needed to further investigate HEV disease courses and extrahepatic manifestations. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - July 11, 2019 Category: Neurology Authors: Diebold, M., Fischer-Barnicol, B., Tsagkas, C., Kuhle, J., Kappos, L., Derfuss, T., Decard, B. F. Tags: Autoimmune diseases, All Clinical Neurology, Viral infections, Multiple sclerosis Article Source Type: research

Randomized, controlled crossover study of IVIg for demyelinating polyneuropathy and diabetes
Conclusions IVIg did not reduce disability, improve strength, or quality of life in patients with demyelinating polyneuropathy features and diabetes after 3 months of treatment in comparison with placebo. Therefore, careful consideration of the primary diagnosis is required before immunomodulatory therapy. Classification of evidence This study provides Class I evidence that for patients with diabetes and demyelinating polyneuropathy features, IVIg did not significantly reduce disability. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - July 10, 2019 Category: Neurology Authors: Breiner, A., Barnett Tapia, C., Lovblom, L. E., Perkins, B. A., Katzberg, H. D., Bril, V. Tags: Peripheral neuropathy, Chronic inflammatory demyelinating polyneuropathy, Clinical trials Randomized controlled (CONSORT agreement), Class I Article Source Type: research

{alpha}4-integrin deficiency in B cells does not affect disease in a T-cell-mediated EAE disease model
(Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - July 5, 2019 Category: Neurology Tags: Correction Source Type: research

Time is tissue in optic neuritis
Once again, this issue of Neurology® Neuroimmunology & Neuroinflammation (N2) highlights the diversity of the field with studies on a range of clinical disorders and a variety of research approaches. Optic neuritis in patients with neuromyelitis optica spectrum disorders associated with aquaporin 4 antibodies (AQP4) or myelin oligodendrocyte glycoprotein (MOG) antibodies is considered steroid responsive, although patients can accumulate disability with recurrent attacks. For these patients, Stiebel-Kalish et al.1 investigated whether the time from symptom onset to steroid treatment affected outcome. This was a retr...
Source: Neurology Neuroimmunology and Neuroinflammation - July 5, 2019 Category: Neurology Authors: Dalmau, J. Tags: Editor ' s Corner Source Type: research

Long-term safety and efficacy of subcutaneous immunoglobulin IgPro20 in CIDP: PATH extension study
Conclusions Subcutaneous treatment with IgPro20 provided long-term benefit at both 0.4 and 0.2 g/kg weekly doses with lower relapse rates on the higher dose. Long-term dosing should be individualized to find the most appropriate dose in a given patient. Classification of evidence This study provides Class IV evidence that for patients with CIDP, long-term treatment with SCIG beyond 24 weeks is safe and efficacious. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - July 3, 2019 Category: Neurology Authors: van Schaik, I. N., Mielke, O., Bril, V., van Geloven, N., Hartung, H.-P., Lewis, R. A., Sobue, G., Lawo, J.-P., Praus, M., Durn, B. L., Cornblath, D. R., Merkies, I. S. J., on behalf of the PATH study group Tags: Chronic inflammatory demyelinating polyneuropathy, Clinical trials Observational study (Cohort, Case control), Class IV Article Source Type: research

Novel clinical features of glycine receptor antibody syndrome: A series of 17 cases
Conclusions Clinicians should consider testing for GlyR antibodies in GAD65 antibody–negative or low-positive GAD65 antibody patients with SPS-like presentations, especially in the setting of atypical features such as visual disturbances, parkinsonism, or epilepsy. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - July 1, 2019 Category: Neurology Authors: Piquet, A. L., Khan, M., Warner, J. E. A., Wicklund, M. P., Bennett, J. L., Leehey, M. A., Seeberger, L., Schreiner, T. L., Paz Soldan, M. M., Clardy, S. L. Tags: All Immunology, Autoimmune diseases, Parkinson's disease/Parkinsonism, Stiff person syndrome Article Source Type: research

Pharmacokinetics and pharmacodynamics of natalizumab in pediatric patients with RRMS
Conclusions PK profile, α4-integrin saturation, lymphocyte counts, and safety observed in these pediatric patients are comparable to those reported in adults. Classification of evidence This study provides Class I evidence that natalizumab PK/PD parameters and safety profile are similar in adults and pediatric patients in the short term. Longer studies, also including a larger number of younger subjects (aged 10–12 years), are required to further inform about long-term PK and PD parameters in pediatric patients with MS. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - July 1, 2019 Category: Neurology Authors: Ghezzi, A., Comi, G., Grimaldi, L. M., Moiola, L., Pozzilli, C., Fantaccini, S., Gallo, P. Tags: All Pediatric, Patient safety, Multiple sclerosis Article Source Type: research

Systemic inflammatory response syndrome and long-term outcome after intracerebral hemorrhage
Objective To investigate whether the systemic inflammatory response syndrome (SIRS) without infection as surrogate of a systemic immune response is associated with poor long-term functional outcome in patients with spontaneous intracerebral hemorrhage (ICH). Methods We analyzed consecutive patients with spontaneous ICH from our prospective cohort study (2018–2015). SIRS was defined according to standard criteria: i.e., 2 or more of the following parameters during hospitalization: body temperature 38°C, respiratory rate>20 per minute, heart rate>90 per minute, or white blood cell count 12,000/μL in the a...
Source: Neurology Neuroimmunology and Neuroinflammation - July 1, 2019 Category: Neurology Authors: Hagen, M., Sembill, J. A., Sprügel, M. I., Gerner, S. T., Madzar, D., Lücking, H., Hölter, P., Schwab, S., Huttner, H. B., Kuramatsu, J. B. Tags: Prognosis, Intracerebral hemorrhage Article Source Type: research

Gray matter microglial activation in relapsing vs progressive MS: A [F-18]PBR06-PET study
Objective To determine the value of [F-18]PBR06-PET for assessment of microglial activation in the cerebral gray matter in patients with MS. Methods Twelve patients with MS (7 relapsing-remitting and 5 secondary progressive [SP]) and 5 healthy controls (HCs) had standardized uptake value (SUV) PET maps coregistered to 3T MRI and segmented into cortical and subcortical gray matter regions. SUV ratios (SUVRs) were global brain normalized. Voxel-by-voxel analysis was performed using statistical parametric mapping (SPM). Normalized brain parenchymal volumes (BPVs) were determined from MRI using SIENAX. Results Cortical SUVRs...
Source: Neurology Neuroimmunology and Neuroinflammation - July 1, 2019 Category: Neurology Authors: Singhal, T., O'Connor, K., Dubey, S., Pan, H., Chu, R., Hurwitz, S., Cicero, S., Tauhid, S., Silbersweig, D., Stern, E., Kijewski, M., DiCarli, M., Weiner, H. L., Bakshi, R. Tags: PET, Multiple sclerosis Article Source Type: research

Collaborative International Research in Clinical and Longitudinal Experience Study in NMOSD
Conclusions Collectively, the CIRCLES experience to date demonstrates this study to be a useful and readily accessible resource to facilitate accelerating solutions for patients with NMOSD. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - June 28, 2019 Category: Neurology Authors: Cook, L. J., Rose, J. W., Alvey, J. S., Jolley, A. M., Kuhn, R., Marron, B., Pederson, M., Enriquez, R., Yearley, J., McKechnie, S., Han, M. H., Tomczak, A. J., Levy, M., Mealy, M. A., Coleman, J., Bennett, J. L., Johnson, R., Barnes-Garcia, M., Traboulse Tags: All Demyelinating disease (CNS), Optic neuritis; see Neuro-ophthalmology/Optic Nerve, Transverse myelitis, Case control studies Article Source Type: research

Tumefactive demyelination in a patient with relapsing-remitting MS on ocrelizumab
We report a case of tumefactive demyelination (TD) in an ocrelizumab-treated patient with RRMS. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - June 26, 2019 Category: Neurology Authors: Moreira Ferreira, V. F., Meredith, D., Stankiewicz, J. M. Tags: Clinical neurology history, Multiple sclerosis Clinical/Scientific Notes Source Type: research

Neuromyelitis optica spectrum disorder: Patient experience and quality of life
Conclusions Collectively, the current findings advance the understanding of physical, emotional, social, and financial tolls imposed by NMOSD. These insights offer potential ways to enhance QoL by managing pain, enhancing family and social networks, and facilitating active employment. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - June 20, 2019 Category: Neurology Authors: Beekman, J., Keisler, A., Pedraza, O., Haramura, M., Gianella-Borradori, A., Katz, E., Ratchford, J. N., Barron, G., Cook, L. J., Behne, J. M., Blaschke, T. F., Smith, T. J., Yeaman, M. R. Tags: Quality of life, Autoimmune diseases, Cohort studies Article Source Type: research

Does CSF pleocytosis have a predictive value for disease course in MS?
Objective MS is a demyelinating CNS disorder with a spectrum of clinical patterns regarding course and prognosis. Although several prognostic factors are considered in the initial evaluation of patients, biological markers defining the disease course and guiding treatments are currently lacking. It is unknown whether patients with CSF pleocytosis differ in regard to symptoms, disease course, and prognosis from those without. The aim of this study was to evaluate whether CSF pleocytosis during the initial presentation has an impact on the clinical course and progression of MS. Methods We retrospectively evaluated patients ...
Source: Neurology Neuroimmunology and Neuroinflammation - June 18, 2019 Category: Neurology Authors: Lotan, I., Benninger, F., Mendel, R., Hellmann, M. A., Steiner, I. Tags: All Immunology, Prognosis, All Demyelinating disease (CNS), Multiple sclerosis Article Source Type: research

Cataclysmically disseminating neurologic presentation in an immunosuppressed lupus patient: From the National Multiple Sclerosis Society Case Conference Proceedings
A 54-year-old woman presented with complaints of myalgias, fatigue, and progressive leg weakness of several weeks duration, followed by acute loss of vision in her left eye. Her medical history was notable for long-standing systemic lupus erythematosus (SLE) that was actively treated with prednisone, mycophenolate mofetil, and quinacrine. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - June 13, 2019 Category: Neurology Authors: Perrone, C. M., Lisak, R. P., Meltzer, E. I., Sguigna, P., Tizazu, E., Jacobs, D., Melamed, E., Lucas, A., Freeman, L., Pardo, G., Goodman, A., Fox, E. J., Costello, K., Parsons, M. S., Zamvil, S. S., Frohman, E. M., Frohman, T. C. Tags: All Infections, Meningitis, Viral infections, Retina, Transverse myelitis Diagnostic and Treatment Challenges Source Type: research

Trial of canakinumab, an IL-1{beta} receptor antagonist, in patients with inclusion body myositis
Conclusions In this long-term, open-label study, canakinumab showed small, but not clinically appreciable, stabilizing benefits in 2 of 5 patients with sIBM over 1 year, was ineffective in 2 others, and might have worsened one. No patient improved. Classification of evidence This study provides Class IV evidence that canakinumab was ineffective for patients with sIBM. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - June 10, 2019 Category: Neurology Authors: Kosmidis, M. L., Pikazis, D., Vlachoyiannopoulos, P., Tzioufas, A. G., Dalakas, M. C. Tags: All Immunology, Muscle disease, Clinical trials Observational study (Cohort, Case control), Class IV Article Source Type: research

Natalizumab treatment reduces microglial activation in the white matter of the MS brain
Conclusions TSPO-PET imaging can be used as a tool to assess longitudinal changes in microglial activation in the NAWM and in the perilesional areas in the MS brain in vivo. Natalizumab treatment reduces the diffuse compartmentalized CNS inflammation related to brain resident innate immune cells. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - June 7, 2019 Category: Neurology Authors: Sucksdorff, M., Tuisku, J., Matilainen, M., Vuorimaa, A., Smith, S., Keitilä, J., Rokka, J., Parkkola, R., Nylund, M., Rinne, J., Rissanen, E., Airas, L. Tags: PET, Multiple sclerosis Article Source Type: research

Cerebellar ataxia as a presenting symptom in a patient with anti-NMDA receptor encephalitis
We report a case of a female adult with anti-NMDAR encephalitis presenting with cerebellar ataxia associated with recurrent mature ovarian teratomas. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - June 4, 2019 Category: Neurology Authors: Poorthuis, M. H. F., van Rooij, J. L. M., Koch, A. H., Verdonkschot, A. E. M., Leembruggen, M. M., Titulaer, M. J. Tags: Autoimmune diseases, Encephalitis, Paraneoplastic syndrome Clinical/Scientific Notes Source Type: research

CSF parameters associated with early MRI activity in patients with MS
Conclusions CSF parameters such as IgG and IgM index are independently associated with future MRI activity and thus might be helpful to support early treatment decisions in patients newly diagnosed with CIS and MS. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - May 30, 2019 Category: Neurology Authors: Klein, A., Selter, R. C., Hapfelmeier, A., Berthele, A., Müller-Myhsok, B., Pongratz, V., Gasperi, C., Zimmer, C., Mühlau, M., Hemmer, B. Tags: MRI, Cerebrospinal Fluid, Multiple sclerosis Article Source Type: research

Immunotherapy improves sleep and cognitive impairment in anti-IgLON5 encephalopathy
Autoimmune encephalopathy associated with immunoglobulin G (IgG) autoantibodies binding to IgLON5 is characterized by a sleep disorder that includes sleep-disordered breathing and parasomnia, accompanied by gait disturbance, bulbar symptoms, dysautonomia, and cognitive decline.1 The effect of immunotherapy in patients with anti-IgLON5 disease remains unclear. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - May 21, 2019 Category: Neurology Authors: Brunetti, V., Della Marca, G., Spagni, G., Iorio, R. Tags: Autoimmune diseases, Encephalitis, Parasomnias Clinical/Scientific Notes Source Type: research

Age matters: Impact of data-driven CSF protein upper reference limits in Guillain-Barre syndrome
Conclusions The low sensitivity of CSF-TP for the diagnosis of GBS is exacerbated by age-adjusted upper limits. The main role of lumbar puncture in GBS in the first week may be to help exclude other inflammatory or neoplastic etiologies of acute neuropathy. After the first week, the magnitude of the CSF-TP rise reduces the effect of different upper reference limits. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - May 21, 2019 Category: Neurology Authors: Bourque, P. R., Brooks, J., McCudden, C. R., Warman-Chardon, J., Breiner, A. Tags: All Clinical Neurology, Peripheral neuropathy, Guillain-Barre syndrome, Cerebrospinal Fluid Article Source Type: research

Guillain-Barre syndrome and related diseases after influenza virus infection
We examined the clinical and serologic features of Guillain-Barré syndrome (GBS)-related diseases (GBSRDs), including GBS, Fisher syndrome (FS), and Bickerstaff brainstem encephalitis (BBE), after influenza virus infection (GBSRD-I) to reveal potential underlying autoimmune mechanisms. Methods We retrospectively investigated the presence of antiglycolipid antibodies against 11 glycolipids and the clinical features of 63 patients with GBSRD-I. Autoantibody profiles and clinical features were compared with those of 82 patients with GBSRDs after Campylobacter jejuni infection (GBSRD-C). Results The anti-GQ1b seroposi...
Source: Neurology Neuroimmunology and Neuroinflammation - May 21, 2019 Category: Neurology Authors: Yamana, M., Kuwahara, M., Fukumoto, Y., Yoshikawa, K., Takada, K., Kusunoki, S. Tags: Guillain-Barre syndrome Article Source Type: research

Does time equal vision in the acute treatment of a cohort of AQP4 and MOG optic neuritis?
Conclusions In this retrospective study of ON with AQP4 and MOG-IgG, even a 7-day delay in IVMP initiation was detrimental to vision. These results highlight the importance of early treatment for the long-term visual recovery in this group of patients. A prospective, multicenter study of the effects of timing of IVMP is currently underway. Classification of evidence This study provides Class IV evidence that hyperacute treatment of AQP4 and MOG-ON with IVMP increases the chance for good visual recovery (20/20 vision) and that even a greater than 7-day delay in treatment is associated with a higher risk for poor visual rec...
Source: Neurology Neuroimmunology and Neuroinflammation - May 21, 2019 Category: Neurology Authors: Stiebel-Kalish, H., Hellmann, M. A., Mimouni, M., Paul, F., Bialer, O., Bach, M., Lotan, I. Tags: Devic's syndrome, Optic neuritis; see Neuro-ophthalmology/Optic Nerve Article Source Type: research

Harmful neutrophil subsets in patients with ischemic stroke: Association with disease severity
Conclusion Altogether, our results indicate that during acute IS, the inflammatory properties of circulating neutrophils rise, associated with the expansion of harmful neutrophil subsets. These changes in neutrophil homeostasis, associated with disease severity, may play an instrumental role by contributing to systemic inflammation and to the blood-brain barrier breakdown. Our findings highlight new potential therapeutic approaches of stroke by rebalancing the ratio of senescent to immunosuppressive neutrophils or decreasing reverse neutrophil transmigration or both. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - May 15, 2019 Category: Neurology Authors: Weisenburger-Lile, D., Dong, Y., Yger, M., Weisenburger, G., Polara, G. F., Chaigneau, T., Ochoa, R. Z., Marro, B., Lapergue, B., Alamowitch, S., Elbim, C. Tags: All Immunology, Infarction Article Source Type: research

Contribution of polymorphonuclear neutrophils in the blood periphery to ischemic brain injury
PMNs abundantly accumulate in ischemic brain tissue in response to stroke both in rodents and human patients, where they massively release enzymes, such as myeloperoxidase and elastase, and reactive oxygen species (ROS), which are known contributors to ischemic injury.1–3 (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - May 15, 2019 Category: Neurology Authors: Hermann, D. M., Gunzer, M. Tags: All Immunology, Infarction Editorial Source Type: research

Immunoglobulin G4-related hypertrophic pachymeningitis: A case-oriented review
Discussion/conclusion IgG4-HP is characterized by the lack of extra-neurologic organ-involvement and systemic signs. Histopathologic studies should be performed as it is crucial for diagnosis because serum markers are rarely informative. 18F-FDG positon tomography can be useful to characterize systemic forms. There is no specific CSF marker for IgG4-HP and the diagnostic value of CSF IgG4 levels needs to be studied with larger samples. We provide a treatment algorithm for IgG4-HP. Such treatment strategies rely on early surgery, steroids, and early immunosuppressive therapy to prevent neurologic complications. (Source: Neu...
Source: Neurology Neuroimmunology and Neuroinflammation - May 7, 2019 Category: Neurology Authors: Levraut, M., Cohen, M., Bresch, S., Giordana, C., Burel-Vandenbos, F., Mondot, L., Sedat, J., Fontaine, D., Bourg, V., Martis, N., Lebrun-Frenay, C. Tags: MRI, All Immunology, Autoimmune diseases, All Medical/Systemic disease, All Spinal Cord Views [amp ] Reviews Source Type: research

Strategies for treatment of childhood primary angiitis of the central nervous system
Objective Childhood primary angiitis of the CNS (cPACNS) is a devastating neurologic disease. No standardized treatment protocols exist, and evidence is limited to open-label cohort studies and case reports. The aim of this review is to summarize the literature and provide informed treatment recommendations. Methods A scoping review of cPACNS literature from January 2000 to December 2018 was conducted using Ovid, MEDLINE, PubMed, Embase, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, Vasculitis Foundation, European Vasculitis Society, CanVasc, Google Scholar, a...
Source: Neurology Neuroimmunology and Neuroinflammation - May 3, 2019 Category: Neurology Authors: Beelen, J., Benseler, S. M., Dropol, A., Ghali, B., Twilt, M. Tags: Autoimmune diseases, Vasculitis, All Pediatric, Pediatric stroke; see Cerebrovascular Disease/ Childhood stroke Views [amp ] Reviews Source Type: research

A surprise with MuSK antibodies
This issue of Neurology® Neuroimmunology & Neuroinflammation (N2) contains several studies that reveal surprising or unexpected findings such as the mechanisms underlying muscle-specific kinase (MuSK) antibody pathogenicity, presence of inflammatory cells in normal muscle, and the isolated CNS manifestation of a systemic disease. Here is a brief overview of these and other studies. (Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - May 2, 2019 Category: Neurology Authors: Dalmau, J. Tags: Editor ' s Corner Source Type: research

Mouse model of anti-NMDA receptor post-herpes simplex encephalitis
(Source: Neurology Neuroimmunology and Neuroinflammation)
Source: Neurology Neuroimmunology and Neuroinflammation - May 2, 2019 Category: Neurology Tags: Correction Source Type: research