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Anti-NMDAR encephalitis is a newly characterized syndrome with a progressive, predictable clinical course and the possibility of effective treatment. Accurate and timely diagnosis is critical to selection and implementation of treatments, and optimal patient outcomes. Outcomes are improved with early diagnosis via indirect immunofluorescence or cell-based assays, and the rapid and appropriate administration of immunosuppressant and anti-psychotic therapies. Three possible scenarios accounting for the immunopathogenesis of anti-NMDAR encephalitis are presented, with the most probable one being that of paraneoplastic autoimmunity. Future efforts in this disorder should focus on elucidating the mechanisms that contribute to initiation of this antibody response, as well as exploring the role of tumors, infectious triggers and immune-reactivation. Finally, accessible tools need to be developed that allow for reliable identification of specific antibody markers against synaptic proteins.

Immune mechanisms are included in stroke pathophysiologic factors, but the frequency and role of intrathecal antibodies is unclear and diagnostic tests are not routinely performed on cerebrospinal fluid (CSF).To determine the frequency of intrathecal immunoglobulin synthesis in a well-characterized cohort of patients who experienced “noninflammatory”acute stroke.Retrospective cohort study.University hospital neurology department.Patients (n=318) with stroke who were undergoing lumbar puncture during diagnostic workup and 79 control patients.Cerebrospinal fluid–specific immunoglobulin(IgG, IgM, and IgA) synthesis was significantly(P.001) more frequent after stroke (24.8%) compared with the incidence in age- and sex-matched controls(2.5%). Furthermore, 31.3% of stroke patients demonstrated blood-brain barrier dysfunction and 18.1% displayed pleocytosis.The strong association between CSF-specific immunoglobulin synthesis and stroke suggests a role in the development of cerebral ischemia and might constitute an immunologically defined stroke subgroup.

Background: In recent years, an increasing number of auto-antibodies (AB) have been detected in the CSF and serum of patients with new onset epilepsy. Some of these patients develop convulsive or nonconvulsive status epilepticus (AB-SE), necessitating intensive medical care and administration of multiple antiepileptic and immunomodulatory treatments of uncertain effectiveness. Objectives: In this retrospective multicenter survey we aimed to determine the spectrum of gravity, the duration and the prognosis of the disorder. In addition, we sought to identify the antibodies associated with this condition, as well as determine whether there is a most effective treatment regime. Methods: 12 European Neurology University Clinics, with extensive experience in the treatment of SE patients, were sent a detailed questionnaire regarding symptoms and treatment of AB-SE patients. Seven centers responded positively, providing a total of 13 patients above the age of 16. Results: AB-SE affects mainly women (12/13, 92%) with a variable age at onset (17–69 years, median: 25 years). The duration of the disease is also variable (10 days to 12 years, median: 2 months). Only the 3 oldest patients died (55–69 years). Most patients were diagnosed with anti NMDAR encephalitis (8/13) and had oligoclonal bands in the CSF (9/13). No specific treatment regimen (antiepileptic, immunomodulatory) was found to be clearly superior. Most of the surviving 10 patients (77%) recovered completely or nearly so within 2 years of index poststatus. Conclusion: AB-SE is a severe but potentially reversible condition. Long duration does not seem to imply fatal outcome; however, age older than 50 years at time of onset appears to be a risk factor for death. There was no evidence for an optimal antiepileptic or immunomodulatory treatment. A prospective multicenter study is warranted in order to stratify the optimal treatment algorithm, determine clear risk factors of unfavorable outcome and long-term prognosis.

Background Anti-NMDA receptor (NMDAR) encephalitis is a recently characterised autoimmune disorder mainly affecting young women. Although the clinical features of the acute disease are well characterised, cognitive long-term outcome has not been examined in detail. Methods The authors investigated cognitive performance in nine patients with proven anti-NMDAR encephalitis after recovery from the acute disease period (median 43 months after disease onset, range 23 to 69). Patients underwent a comprehensive neuropsychological assessment, including memory tasks that have previously been shown to be sensitive for hippocampal dysfunction. Results Substantial persistent cognitive impairments were observed in eight out of nine patients that mainly consisted of deficits in executive functions and memory. The severity of these deficits varied inter-individually. Patients with early immunotherapy performed significantly better. The most severe deficits were observed with inefficient or delayed initial treatment. Conclusion Our results suggest that cognitive deficits constitute a major long-term morbidity of anti-NMDAR encephalitis. These deficits relate to the distribution of NMDARs in the human brain and their functional role in normal cognition. Good cognitive long-term outcome may depend on early and aggressive treatment.

Motor neurons are large cholinergic neurons located in the brain stem and spinal cord. In recent years, a functional role for TASK channels in cellular excitability and vulnerability to anesthetics of motor neurons has been described. Using a polyclonal monospecific antibody against the tandem pore domain K(+) channel (K2P channel) TWIK-related acid-sensitive K(+) channel (TASK-3), we analyzed the expression of the TASK-3 protein in motor systems of the rat CNS. Immunocytochemical staining showed strong TASK-3 expression in motor neurons of the facial, trigeminal, ambiguus, and hypoglossal nuclei. Oculomotor nuclei (including trochlear and abducens nucleus) were also strongly positive for TASK-3. The parasympathetic Edinger-Westphal nucleus and dorsal vagal nucleus showed significant, but weaker expression compared with somato- and branchiomotoric neurons. In addition, motor neurons in the anterior horn of the spinal cord were also strongly labeled for TASK-3 immunoreactivity. Based on morphological criteria, TASK-3 was found in the somatodendritic compartment of motor neurons. Cellular staining using methyl green and immunofluorescence double-labeling with anti-vesicular acetylcholine transporter (anti-vAChT) indicated ubiquitous TASK-3 expression in motor neurons, whereas in other brain regions TASK-3 showed a widespread but not ubiquitous expression. In situ hybridization using a TASK-3 specific riboprobe verified the expression of TASK-3 in motor neurons at the mRNA level.

Inflammatory resolution is an active, highly regulated process already encoded at the onset of inflammation and required to prevent the transition into chronic inflammation associated with spreading of tissue injury and exacerbated scarring. We introduce objective, quantitative measurements [resolution indices (R(i) ) and resolution plateau (R(P) )] to characterize inflammatory resolution and to determine the persistence ("dwell time") of differential leukocyte subpopulations at the lesion site after acute experimental spinal cord injury (SCI). The cell type-specific resolution interval R(i) (time between maximum cell numbers and the point when they are reduced to 50%) ranges from 1.2 days for neutrophils, 1.5 days for T lymphocytes, to 55 days for microglia/macrophages. As the resolution interval neglects exiting cell trafficking in the later period of resolution (49%-0% of lesional cells), we introduced the R(P) , a marker for the persisting, chronified leukocyte subsets, which are likely to participate in late degeneration and non-resolving inflammation. Here, we identify the acute inflammatory response in central nervous system (CNS) lesions as partly non self-limiting. Both extended resolution intervals (reduced leukocyte clearance) and elevated plateaus (permanent lesional cell numbers) provide quantitative measures to characterize residual, sustained inflammation and define cognate timeframes of impaired resolution after acute SCI.

Neural progenitor cells (NPCs) are a source of new neurons and glia in the adult brain. Most NPCs reside in the forebrain subventricular zone (SVZ) and in the subgranular zone of the dentate gyrus, where they contribute to plasticity in the adult brain. To use their potential for repair, it is essential to identify the molecules that regulate their growth, migration and differentiation. Potassium (K+) channels are promising molecule candidates for NPC regulation as they are important components of signal transduction and their diversity is ideal to cover the complex functions required for cell proliferation and differentiation. There is increasing evidence that K+ channels influence cell growth and neurogenesis, however, very little is known regarding K+ channel distribution in NPCs. We therefore explored the expression of a variety of voltage-gated (Kv), inwardly rectifying (Kir) and two-pore (K2P) K+ channels in the SVZ of adult mice and in neurosphere cultures of NPCs during growth and differentiation. Immunocytochemical analysis revealed a differential expression pattern of K+ channels in nestin+ SVZ precursor cells, early SVZ doublecortin+ neurons and (sub)ependymal cells. These findings were confirmed in neurosphere cultures at the protein and mRNA levels. The expression of some K+ channel proteins, such as Kir4.1, Kir6.1, TREK1 or TASK1, suggests a role of K+ channels in the complex regulation of NPC proliferation, maturation and differentiation.

Monoaminergic and cholinergic systems are important regulators of cortical and subcortical systems, and a variety of vegetative functions are controlled by the respective neurotransmitters. Neuronal excitability and transmitter release of these neurons are strongly regulated by their potassium conductances carried by Kir and K(2P) channels. Here we describe the generation and characterization of a polyclonal monospecific antibody against rat TASK-3, a major brain K(2P) channel. After removal of cross-reactivities and affinity purification the antibody was characterized by ELISA, immunocytochemistry of TASK-3 transfected cells, and Western blots indicating that the antibody only detects TASK-3 protein, but not its paralogs TASK-1 and TASK-5. Western blot analysis of brain membrane fractions showed a single band around 45 kD, close to the predicted molecular weight of the TASK-3 protein. In addition, specific immunolabeling using the anti-TASK-3 antibody in Western blot analysis and immunocytochemistry was blocked in a concentration dependent manner by its cognate antigen only. Immunocytochemical analysis of rat brain revealed strong expression of TASK-3 channels in serotoninergic neurons of the dorsal and median raphe, noradrenergic neurons of the locus coeruleus, histaminergic neurons of the tuberomammillary nucleus and in the cholinergic neurons of the basal nucleus of Meynert. Immunofluorescence double-labeling experiments with appropriate marker enzymes confirmed the expression of TASK-3 in cholinergic, serotoninergic, and noradrenergic neurons. In the dopaminergic system strong TASK-3 expression was found in the ventral tegmental area, whereas TASK-3 immunoreactivity in the substantia nigra compacta was only weak. All immunocytochemical results were supported by in situ hybridization using TASK-3 specific riboprobes.

Semaphorin 7A (Sema7A) is involved in the formation of the central nervous system during development by operating axon guidance and neuronal migration. We investigated the expression of the TGFβ-inducible Sema7A following spinal cord injury (SCI). After SCI, Sema7A(+) cells accumulated specifically in lesion areas resulting in significantly enhanced Sema7A expression at the injury site (P < 0.0001). During the first days lesional Sema7A expression was confined to neurons, ballooned neurite fibers/retraction bulbs, and endothelial cells. At day 7, we observed Sema7A expression by components of the glial scar, such as reactive astrocytes and pronounced extracellular Sema7A deposition. In the direct perilesional rim, Sema7A(+) astrocytes coexpressed the activation-associated intermediate filament vimentin. In the injured spinal cord, numbers of Sema7A(+) cells reached maximum levels at day 14. The restricted accumulation of Sema7A(+) reactive astrocytes and Sema7A deposition in fibronectin(+) extracellular matrix territories suggests a participation of the fibrostimulatory Sema7A in the developing and maturating scar following SCI. In addition, Sema7A appears to be marker a for astrocyte activation.

Agmatinase, an ureohydrolase belonging to the arginase family, is widely expressed in mammalian tissues including the brain. Here, it may serve two different functions, the inactivation of the arginine derivative agmatine, a putative neurotransmitter, and the formation of the diamine putrescine. In order to identify the cellular sources of agmatinase expression in the brain, we generated a polyclonal monospecific antibody against recombinant rat agmatinase. With immunocytochemistry, selected areas of rat and human brain were screened. Clearly, in both species agmatinase-like immunoreactivity was predominantly detected in distinct populations of neurons, especially cortical interneurons. Also, principal neurons in limbic regions like the habenula and in the cerebellum robustly expressed agmatinase protein. When comparing the overall agmatinase expression with immunocytochemical data available for agmatine and polyamine biosynthetic enzymes, the observed pattern may argue in favor of an agmatine inactivating function rather than fueling the alternative pathway of polyamine synthesis. The putative neurotransmitter agmatine is seemingly involved with mental disorders. Therefore, agmatinase may be similarly important for pathogenesis. The normal expression profile of the protein as described here may therefore be altered under pathological conditions.

Large conductance Ca(2+)-activated BK channels are important regulators of action potential duration and firing frequency in many neurons. As the pore-forming subunits of BK channels are encoded by a single gene, channel diversity is mainly generated by alternative splicing and interaction with auxiliary beta-subunits (BKbeta1-4). In hypothalamic neurons several BK channel subtypes have been described electrophysiologically; however, the distribution of BKbeta subunits is unknown so far. Therefore, an antibody against the large extracellular loop of the BKbeta1 subunit was raised, freed from cross-reactivity against BKbeta2-4 and affinity-purified. The resulting polyclonal monospecific BKbeta1 antibody was characterized by Western blot analysis, ELISA techniques and immunocytochemical staining of BKbeta1-4-transfected CHO and COS-1 cells. Regional and cellular distribution in the rat hypothalamus was analysed by immunocytochemistry and in situ hybridization experiments. Immunocytochemical staining of rat hypothalamic neurons indicates strong BKbeta1 expression in the supraoptic nucleus and the magno- and parvocellular parts of the paraventricular nucleus. Lower expression was found in periventricular nucleus, the arcuate nucleus and in the median eminence. Immunostaining was predominantly localized to somata. In addition, pericytes and ependymal epithelial cells showed BKbeta1 labelling. In all cases immunocytochemical results were supported by in situ hybridization.

The serotonergic system of the brainstem raphe is involved in mood control, the sleep-wake cycle, autonomic function, and stress response. The axons of certain dorsal raphe neurons form a dense serotonergic supraependymal plexus lining the brain ventricles, likely regulating ependymal metabolism and activity including ciliary movements and glucose homeostasis. In raphe neurons, serotonin exerts its function partly via 5-HT autoreceptors and G protein-gated inwardly rectifying potassium channels (Kir3/GIRK). To consider a similar mechanism in supraependymal fibres we examined immunocytochemically the distribution of Kir3 potassium channel subunits on supraependymal axons. In the present study, we show that the Kir3.3 subunit protein is expressed in raphe-derived axons at the light and electron microscopic level, but none of the other Kir3 subfamily members or the K(ATP) channel subunits Kir6.1 and Kir6.2. Thus, Kir3.3 containing potassium channels may be of functional importance in autoregulation and excitability of supraependymal fibres and the complex serotonergic regulation along the parenchyma/CSF border.

A 22-year-old woman with mitochondriopathy and pre-existing epilepsy developed status epilepticus (SE) not responding to benzodiazepines, phenytoin, thiopental, and propofol. SE was terminated within days after supplemental administration of continuous ketamine infusion to midazolam. The case suggests strong anticonvulsant properties of ketamine even after failure of GABAergic anesthetics, likely due to increased NMDA receptor expression with ongoing seizure activity. Thus, ketamine should be incorporated into therapeutic regimens for difficult-to-treat SE.

Whipple disease is a granulomatous infectious disease caused by Tropheryma whipplei. The bacteria accumulate within macrophages, preferentially in the intestinal mucosa. Disease manifestation seems to be linked to immunological abnormalities of macrophages. We describe a patient with cerebral Whipple disease who presented with changes in mental status, confusion, inverse sleep-wake cycle, bilateral ptosis and vertical gaze palsy. Endoscopic biopsy sampling revealed Whipple disease in the gastric antrum but not in the duodenum. Whole blood stimulation displayed reactivity to T. whipplei that was at the lower end of healthy controls while reactivity of duodenal lymphocytes was not diminished. We propose that in cases of neurological symptoms suspicious of Whipple disease with normal duodenal and jenunal findings, biopsy sampling should be extended to the gastric mucosa. The robust reactivity of duodenal lymphocytes may have prevented our patient from developing small bowel disease, whereas the impaired reactivity in peripheral blood lymphocytes might yet explain the bacterial spreading to the central nervous system leading to the rare case of predominant neurological symptoms without relevant systemic involvement.

Editors' Note: In WriteClick this week, Drs. Finke and Pruss comment on influenza-associated encephalitis (IAE) as discussed in “Clinical Reasoning: A 57-year-old woman who developed acute amnesia following fever and upper respiratory symptoms,” and suggest patients with suspected IAE be tested for neuronal antibodies. In reference to “Spatial cluster analysis of population amyotrophic lateral sclerosis risk in Ireland,” …

K-ATP channels consist of two structurally different subunits: a pore-forming subunit of the Kir6.0-family (Kir6.1 or Kir6.2) and a sulfonylurea receptor (SUR1, SUR2, SUR2A, SUR2B) with regulatory activity. The functional diversity of K-ATP channels in brain is broad and of fundamental importance for neuronal activity. Here, using immunocytochemistry with monospecific antibodies against the Kir6.1 and Kir6.2 subunits, we analyze the regional and cellular distribution of both proteins in the adult rat brain. We find Kir6.2 to be widely expressed in all brain regions, suggesting that the Kir6.2 subunit forms the pore of the K-ATP channels in most neurons, presumably protecting the cells during cellular stress conditions such as hypoglycemia or ischemia. Especially in hypothalamic nuclei, in particular the ventromedial and arcuate nucleus, neurons display Kir6.2 immunoreactivity only, suggesting that Kir6.2 is the pore-forming subunit of the K-ATP channels in the glucose-responsive neurons of the hypothalamus. In contrast, Kir6.1-like immunolabeling is restricted to astrocytes (Thomzig et al. [2001] Mol Cell Neurosci 18:671-690) in most areas of the rat brain and very weak or absent in neurons. Only in distinct nuclei or neuronal subpopulations is a moderate or even strong Kir6.1 staining detected. The biological functions of these K-ATP channels still need to be elucidated.

Tension pneumocephalus results from intracranial air under pressure as a rare complication after head injury or craniofacial surgery. A 58-year-old man underwent ethmoid sinus surgery and subsequently developed rapidly progressive global headache, restlessness, diplegia with sensory loss, and deterioration of the conscious level. A head CT demonstrated extensive pneumocephalus with gross compression of the brain. The frontal retention of air caused widening of the interhemispheric fissure leading to a peaked appearance of the frontal poles, referred to as the ‘Mount Fuji sign’. Surgical revision of a dural air leak resulted in rapid improvement and full clinical resolution. Early diagnosis of tension pneumocephalus and emergent surgical treatment are crucial to prevent life-threatening deterioration.

Deficiency of mitochondrial DNA polymerase γ (POLG), which is responsible for mtDNA replication and repair, causes mitochondrial diseases including autosomal dominant progressive external ophthalmoplegia (PEO),1 childhood hepato-encephalopathy (Alpers–Huttenlocher syndrome), adult-onset spinocerebellar ataxia, and sensory nerve degeneration with dysarthria and ophthalmoparesis (SANDO).2 3 Two siblings of non-consanguineous healthy Vietnamese parents were normal until childhood (fig 1A,B). Figure 1 (A) Clinical course of the sister (II.3) and the brother (II.2) with MRI of the sister revealing cortical lesions and cerebellar T2-hyperintensities (arrow) and the brother’s MRI showing leucoencephalopathy and cerebellar T2-hyperintensities. (B) Family pedigree with polymerase γ 1 (POLG1) mutations. Squares represent males, circles females, filled symbols affected and slashed symbols deceased individuals. (C) Mutant residues in POLG1 and amino-acid alignment showing evolutionary conservation of altered residues. Patient II.2, the 27-year-old male, developed from the age of 15 progressive cerebellar ataxia, neuropathy, restless legs syndrome, on two occasions a transient left hemihypesthesia and four focal myoclonic epileptic seizures and received lamotrigine. He became wheelchair-bound at 22 because of severe ataxia. By 25, he developed dysphagia and weight loss. Muscle strength was preserved. No external ophthalmoplegia or cognitive deficits occurred. After discontinuing lamotrigine, he exhibited grand maux, requiring combination treatment. He became anxious and complained of migrainous headaches and abdominal pain. Soon after, he died after prolonged status epilepticus. Lactate-ischaemia ergometry at age 20 was unremarkable. In serum, lactate and CK (244 U/l) were mildly elevated. In CSF, …

Sirs, Neurological symptoms of uremic encephalopathy result from cerebral edema and include deterioration of conscious level, headache, myoclonus, tremor, and seizures [9]. To distinguish between vasogenic and cytotoxic edema, diffusion-weighted brain magnetic resonance imaging (MRI) can be performed. Because vasogenic edema is predominant in uremic patients, as opposed to cytotoxic edema, prompt treatment may allow regression of cellular damage and clinical symptoms [4, 11]. We report the first case of nondiabetic uremic encephalopathy with focal neurological deficits and cytotoxic edema. However, despite neuroradiological signs of cytotoxicity, immediate therapy resulted in full recovery of neurological signs and MR changes. A 46-year-old woman with no past medical history presented with subacute onset of left facial weakness, confusion, and nonfluent aphasia. Initial MRI showed bilateral confluent areas of T2 hyperintensity involving the complete supratentorial white matter without cortical involvement. Diffusion-weighted imaging (DWI) revealed hyperintense signal alterations with reduced apparent diffusion coefficient (ADC) values indicative of diffusion restriction (Fig. 1). Laboratory examination revealed excessive blood urea nitrogen (220 mg/dl) and creatinine levels (6.9 mg/dl); blood pressure was only slightly elevated (\140 mmHg). The neurological impairment of our patient rapidly improved after continuous hemodialysis over 12 h with full recovery after 1 day. Blood urea nitrogen level was 33 mg/ dl after 72 h. Follow-up MRI after 18 days demonstrated complete resolution of the diffusion abnormalities. The cause of renal failure remained unclear, as the patient refused renal biopsy. However, a hereditary glomerulonephritis was suspected, as several family members needed chronic hemodialysis or had proteinuria. Diabetes and rheumatologic kidney diseases were excluded. Only few reports describe brain DWI changes in uremic patients and the effect of hemodialysis on neuroimaging [4, 11]. They suggest the presence of interstitial vasogenic edema as opposed to cytotoxic edema. Thus, unusual for uremic encephalopathy, our patient presented with bilateral cytotoxic edema similar to brain ischemia. The distinction was possible by using diffusion-weighted MRI which revealed decreased ADC values indicative of diffusion restriction. In contrast, increased ADC values would have represented vasogenic edema. However, immediate therapy with hemodialysis resulted in full recovery of neurological symptoms. To our knowledge, similar reversibility of diffusion abnormalities has not been demonstrated for uremic encephalopathy. It is however known in other pathologies such as transient cerebral ischemia [6], methotrexate-induced neurotoxicity [7] or reversible posterior leukoencephalopathy syndrome [2]. Uremic encephalopathy may be a cause of reversible posterior leukoencephalopathy syndrome (RPL) [8]. Here, however, the patient not only lacked typical clinical symptoms such as headache, seizures or visual loss [8], but also characteristic cortical lesions on MRI [3] or predisposing factors such as high blood pressure, eclampsia, diabetes or immunosuppressive drugs [10]. Also, in most cases of RPL, vasogenic interstitial edema with increased H. Pruss (&) F. Masuhr Department of Neurology, Charite, University Medicine Berlin, Campus Mitte, Chariteplatz 1, 10117 Berlin, Germany e-mail: harald.pruess@charite.de

Anti-Ta-associated encephalitis is a paraneoplastic inflammatory brain disorder with immune-mediated neurological symptoms. The well-characterised onconeuronal antibody, anti-Ta, reacts with the paraneoplastic protein PNMA2 (former antibody name: anti-Ma2). 1 Neurological symptoms often include abnormalities in eye movement, short-term memory loss, seizures, irritability, personality change or confusion.2,3 The symptoms tend to precede tumour diagnosis and are often more debilitating than the malignancy itself.2 The first study of anti-Ta-related paraneoplastic encephalitis reported 10 young men with testicular cancer.3 Other tumours occur in females4 and approximately 30 cases have been reported.2,5 Several tumours express the protein that, in healthy adults, is restricted to brain and testicular germ cells.3 In contrast to other paraneoplastic syndromes, a remarkable number of patients show neurological improvement if the underlying tumour allows complete surgical resection.2 We report a patient’s history of anti-Ta-associated neurological syndrome with atypical parkinsonism and massive rigidity due to occult testicular cancer. In 2001, a 66-year-old man suddenly developed disorientation, restlessness, psychomotor agitation and fever. A bradykinetic syndrome with rigidity was noted. Verbal output was reduced and the patient responded only in short sentences. Head CT and lumbar puncture examinations were normal, and EEG demonstrated a right temporal epileptic focus. After 2 weeks, the patient was admitted to the Department of Neurology, Charite, University Medicine Berlin, Berlin, Germany, with further neurological deterioration. He was drowsy, with markedly reduced verbal output, and only occasionally followed simple …

Anti-NMDA receptor (NMDAR) encephalitis is a well-recognized immunotherapy-responsive condition, often diagnosed in younger individuals with characteristic clinical symptoms. In women, ovarian teratomas are frequently found and thought to trigger the antibody response against the NMDAR by ectopically expressing neuronal antigens. The present study describes the case of a patient with HSV encephalitis (HSVE) who develops a second episode of neurologic abnormalities, which is in fact NMDAR encephalitis.(1.)

ARTICLE Sir, We have read with great interest the McGonigal et al . (2010) article, which addresses the pathogenic role of GD1a antibodies and complement activation for node of Ranvier dysfunction. Nodal injury might explain several electrophysiological features and clinical symptoms in patients with Guillain–Barre syndrome including the sometimes rapid recovery from paralysis. In our opinion, the reported mechanisms by which loss of axonal conduction can occur, may account not only for GD1a, but also for further nodal proteins once patients with Guillain–Barre syndrome develop antibodies against them. We therefore analysed sera from patients with Guillain–Barre syndrome for the presence of autoantibodies against two important nodal targets, neurofascin and …

A 50-year-old woman presented with a 10-year-history of paroxysmal attacks of severe rotational vertigo lasting seconds without hearing loss or tinnitus, occurring approximately once monthly. MRI revealed megadolichobasilar artery and white-matter lesions (figure, A). Figure. (A) T2-weighted axial MRI shows asymmetric, widespread, hyperintense white-matter lesions. (B, C) Three-dimensional-CISS …

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Beta variant of concern (VOC) resists neutralization by major classes of antibodies from COVID-19 patients and vaccinated individuals. In this study, serum of Beta-infected patients revealed reduced cross-neutralization of wild-type virus. From these patients, we isolated Beta-specific and cross-reactive receptor-binding domain (RBD) antibodies. The Beta-specificity results from recruitment of VOC-specific clonotypes and accommodation of mutations present in Beta and Omicron into a major antibody class that is normally sensitive to these mutations. The Beta-elicited cross-reactive antibodies share genetic and structural features with wild type–elicited antibodies, including a public VH1-58 clonotype that targets the RBD ridge. These findings advance our understanding of the antibody response to SARS-CoV-2 shaped by antigenic drift, with implications for design of next-generation vaccines and therapeutics.

Background Natural killer (NK) cells comprise the main components of lymphocyte-mediated nonspecific immunity. Through their effector function they play a crucial role combating bacterial and viral challenges. They are also thought to be key contributors to the systemic spinal cord injury-induced immune-deficiency syndrome (SCI-IDS). SCI-IDS increases susceptibility to infection and extends to the post-acute and chronic phases after SCI. Methods and design The prospective study of NK cell function after traumatic SCI was carried out in two centers in Berlin, Germany. SCI patients and control patients with neurologically silent vertebral fracture also undergoing surgical stabilization were enrolled. Furthermore healthy controls were included to provide reference data. The NK cell function was assessed at 7 (5–9) days, 14 days (11–28) days, and 10 (8–12) weeks post-trauma. Clinical documentation included the American Spinal Injury Association (ASIA) impairment scale (AIS), neurological level of injury, infection status, concomitant injury, and medications. The primary endpoint of the study is CD107a expression by NK cells (cytotoxicity marker) 8–12 weeks following SCI. Secondary endpoints are the NK cell’s TNF-α and IFN-γ production by the NK cells 8–12 weeks following SCI. Discussion The protocol of this study was developed to investigate the hypotheses whether i) SCI impairs NK cell function throughout the post-acute and sub-acute phases after SCI and ii) the degree of impairment relates to lesion height and severity. A deeper understanding of the SCI-IDS is crucial to enable strategies for prevention of infections, which are associated with poor neurological outcome and elevated mortality. Trial registration DRKS00009855.

Background Infections are the leading cause of death in the acute phase following spinal cord injury and qualify as independent risk factor for poor neurological outcome (“disease modifying factor”). The enhanced susceptibility for infections is not stringently explained by the increased risk of aspiration in tetraplegic patients, neurogenic bladder dysfunction, or by high-dose methylprednisolone treatment. Experimental and clinical pilot data suggest that spinal cord injury disrupts the balanced interplay between the central nervous system and the immune system. The primary hypothesis is that the Spinal Cord Injury-induced Immune Depression Syndrome (SCI-IDS) is 'neurogenic’ including deactivation of adaptive and innate immunity with decreased HLA-DR expression on monocytes as a key surrogate parameter. Secondary hypotheses are that the Immune Depression Syndrome is i) injury level- and ii) severity-dependent, iii) triggers transient lymphopenia, and iv) causes qualitative functional leukocyte deficits, which may endure the post-acute phase after spinal cord injury. Methods/Design SCIentinel is a prospective, international, multicenter study aiming to recruit about 118 patients with acute spinal cord injury or control patients with acute vertebral fracture without neurological deficits scheduled for spinal surgery. The assessment points are: i)