Topic: Infectious Disease of Central Nervous System| Open Access

Current diagnosis and treatment of cryptococcal meningitis without acquired immunodeficiency syndrome

Xiao-Su Guo , Hui Bu , Jun-Ying He , Yue-Li Zou , Yue Zhao , Yuan-Yuan Li , Jun-Zhao Cui , Ming-Ming Zheng , Wei-Xin Han , Ze-Yan Zhao

Cryptococcal meningitis (CM) is a central nervous system infectious disease caused by Cryptococcus. It is the most common fungal infection in the central nervous system, accounting for about 48% of fungal infection. The disease occurs mainly in acquired immunodeficiency syndrome (AIDS) patients... Read more

Cryptococcal meningitis (CM) is a central nervous system infectious disease caused by Cryptococcus. It is the most common fungal infection in the central nervous system, accounting for about 48% of fungal infection. The disease occurs mainly in acquired immunodeficiency syndrome (AIDS) patients and concentrates in the immunocompromised people without AIDS. There are nearly one million new cases of CM each year, and about 70% of them died. In China, CM occurs mainly in people without AIDS and there is an increasing trend in recent years. Early diagnosis and treatment is the key to reducing morbidity and mortality associated with CM. The diagnosis mainly depends on laboratory examination such as morphological examination, fungal culture and antigen detection. History, clinical manifestation and imaging examination are the important parts of auxiliary examination. The initial combined antifungal treatment is emphasized, and the principle of fractional treatment including induction, consolidation and maintenance therapy should be followed. The high intracranial pressure must be reduced actively at the same time. In addition, it is proved that the novel immunotherapy combined with antifungal agents can improve the curative effect and limit the chance of antimicrobial resistance. Large-scale clinical trials are needed for further study. Back

Neuroimmunol Neuroinflammation 2016;3:249-56. | doi:10.20517/2347-8659.2016.10 HTML PDF

Review| Open Access

Neurological manifestations in Fabry disease

Joseph Bruno Bidin Brooks , Yara Dadalti Fragoso

Fabry disease (FD) is a rare, progressive, multisystem and highly debilitating disease. FD is an X-linked lysosome storage disorder that results in α-galactosidase A deficiency. The subsequent accumulation of glycosphingolipids is more evident in vascular endothelium and smooth-muscle cells. The... Read more

Fabry disease (FD) is a rare, progressive, multisystem and highly debilitating disease. FD is an X-linked lysosome storage disorder that results in α-galactosidase A deficiency. The subsequent accumulation of glycosphingolipids is more evident in vascular endothelium and smooth-muscle cells. The resulting effect of the deposition is generalized inflammation and vasculopathy, which can also affect the central and peripheral nervous system. FD progresses with kidney dysfunction, angiokeratoma of the skin, cardiomyopathy, cerebrovascular events and neurological disorders. In the present review, the neurological manifestations of FD are summarized with emphasis on cerebral vasculopathy, cochlear nerve dysfunction, psychiatric and cognitive symptoms, autonomic dysfunction and peripheral neuropathy. Enzyme replacement therapy is also discussed in the light of its more prominent effects when administered early in life, which make it essential to diagnose FD as soon as possible. Back

Neuroimmunol Neuroinflammation 2016;3:228-31. | doi:10.20517/2347-8659.2016.36 HTML PDF

Editorial| Open Access

On the need to unify neuroscience and physics

Maurits van den Noort , Sabina Lim , Peggy Bosch Neuroimmunol Neuroinflammation 2016;3:271-3. | doi:10.20517/2347-8659.2016.55 HTML PDF

Review| Open Access

Immune-to-brain signaling and substrates of altered behavior during inflammation

Jan Pieter Konsman

During the systemic inflammatory response to acute infection, and when in a safe environment, endothermic mammals typically display reduced activity and food intake, increased sleep, and the adoption of a curled-up position. These changes in behavior, in concert with fever, are adaptive in that... Read more

During the systemic inflammatory response to acute infection, and when in a safe environment, endothermic mammals typically display reduced activity and food intake, increased sleep, and the adoption of a curled-up position. These changes in behavior, in concert with fever, are adaptive in that they contribute to host survival. The present review addresses the immune-to-brain signaling pathways as well as possible neural substrates mediating reduced exploration and food intake during acute systemic inflammation. These involve rapid activation of peripheral nerves and glutamatergic brainstem circuits as well as slower IL-1β action in the brain activating limbic and possibly ventral hypothalamic structures. Although mostly adaptive acutely, behavioral changes during inflammation may also reflect brain dysfunction in severe sepsis-associated delirium or become maladaptive and result in depression due to medical conditions that involve long-term inflammatory episodes with pain or discomfort. The mechanisms underlying these conditions are presently ill-understood even though neuroinflammation and neurodegeneration occur during and subsequent to sepsis-associated brain dysfunction, respectively. Back

Neuroimmunol Neuroinflammation 2016;3:207-14. | doi:10.20517/2347-8659.2016.19 HTML PDF

Review| Open Access

The association between human cytomegalovirus and glioblastomas: a review

Christian B. Hochhalter , Christopher Carr , Brannan E. O’Neill , Marcus L. Ware , Michael J. Strong

Human cytomegalovirus (HCMV) was reported in glioblastoma multiforme (GBM) over a decade ago and this finding has the potential to increase our understanding of the disease and it offers an alternative tumor-specific therapeutic target. Due of this promise, there is a fair amount of time, energy... Read more

Human cytomegalovirus (HCMV) was reported in glioblastoma multiforme (GBM) over a decade ago and this finding has the potential to increase our understanding of the disease and it offers an alternative tumor-specific therapeutic target. Due of this promise, there is a fair amount of time, energy and money being directed towards understanding and utilizing this connection for eventual therapeutic purposes. Nevertheless, the association between GBM and HCMV remains controversial. Several studies have reported conflicting results, further undermining the potential clinical value of this association. In this review, the authors will discuss the latest developments on this evolving issue. Specifically, the results of the latest studies, both positive and negative, will be discussed. Furthermore, potential theories to explain discrepancies reported in the literature will be proposed. Clinical implications including potential targets for anti-HCMV therapy and the latest developments in anti-HCMV therapy will be presented. Finally, solutions to remedy this controversial issue in neuro-oncology will be offered. Back

Neuroimmunol Neuroinflammation 2017;4:96-108. | doi:10.20517/2347-8659.2017.10 HTML PDF

Editorial| Open Access

Endocannabinoid metabolism in neurodegenerative diseases

Chu Chen Neuroimmunol Neuroinflammation 2016;3:268-70. | doi:10.20517/2347-8659.2016.46 HTML PDF

Topic: Infectious Disease of Central Nervous System| Open Access

A review with comments on herpes simplex encephalitis in adults

Xu-Zheng Zuo , Wei-Ju Tang , Xiu-Ying Chen , Wen Huang

Herpes simplex encephalitis (HSE) can cause permanent injury to the brain parenchyma. As such, it is usually treated as a medical emergency for which correct immediate diagnosis and introduction of specific therapies are critical for survival and prognosis. Here, the authors review the current... Read more

Herpes simplex encephalitis (HSE) can cause permanent injury to the brain parenchyma. As such, it is usually treated as a medical emergency for which correct immediate diagnosis and introduction of specific therapies are critical for survival and prognosis. Here, the authors review the current status of diagnosis and treatments and discuss unsolved issues surrounding therapeutic interventions. The authors also highlight the current expectations for future management of HSE. Back

Neuroimmunol Neuroinflammation 2017;4:24-7. | doi:10.20517/2347-8659.2016.34 HTML PDF

Topic: Infectious Disease of Central Nervous System| Open Access

Screening of genetic loci predisposing to herpes simplex virus infection on mouse chromosome 17

Xiu-Ying Chen , Wei-Ju Tang , Xu-Zheng Zuo , Gong Wang , Hao-Xiang Wang , Peng Xie , Wen Huang

Aim: The herpes simplex virus (HSV), one of the most common viruses infecting humans, is featured by a high infection rate and usually causes complex disorders difficult to diagnose and treat. Disease progression is always combined with the specific interaction between organism and environment,... Read more

Aim: The herpes simplex virus (HSV), one of the most common viruses infecting humans, is featured by a high infection rate and usually causes complex disorders difficult to diagnose and treat. Disease progression is always combined with the specific interaction between organism and environment, but genetic factors play a decisive role in most pathogenic processes. Like most human disorders, individual difference has also been involved in the pathogenesis of HSV infection. The present study aimed to screen the potential gene loci that regulates human predisposition to HSV infection. Methods: With reference to previous studies, inbred mouse lines with significantly distinct predisposition to HSV infection were chosen for gene loci screening. Gene sites on mouse chromosome 17 associated with susceptibility to HSV infection were then identified by correlation analysis and genome-wide scanning technique. Results: Genes affecting the vulnerability of mice to HSV infection were mapped to three regions on the 17th mouse chromosome, D17MIT51.1, D17MIT39.1 and the region between D17MIT180.1 and D17MIT184. Conclusion: The results suggest that the mouse genetic background plays an important role in its susceptibility to HSV-1 infection, which might be regulated by multiple predisposing quantitative trait loci. Back

Neuroimmunol Neuroinflammation 2016;3:274-82. | doi:10.20517/2347-8659.2016.21 HTML PDF

Topic: Stroke| Open Access

Role of neuroinflammation in ischemic stroke

Rui Liu , Meng-Xian Pan , Jun-Chun Tang , Ya Zhang , Hua-Bao Liao , Yang Zhuang , Dan Zhao , Qi Wan

Ischemic stroke causes the depletion of energy and induce excitotoxicity and neuroinflammation in the brain that results from thrombotic blockage. Neuroinflammation occurs initially depending on activated resident microglia that has the same function as the macrophage. Activated microglia... Read more

Ischemic stroke causes the depletion of energy and induce excitotoxicity and neuroinflammation in the brain that results from thrombotic blockage. Neuroinflammation occurs initially depending on activated resident microglia that has the same function as the macrophage. Activated microglia participates in the neuroinflammatory process by phagocytosing the injured brain cells and producing the pro- and anti-inflammatory mediators. In this review, the authors present an overview of the role of microglia in mediating neuroinflammation in ischemic stroke. Back

Neuroimmunol Neuroinflammation 2017;4:158-66. | doi:10.20517/2347-8659.2017.09 HTML PDF

Case Report| Open Access

Parasellar extra-axial cavernoma mimicking meningioma: a case report

Arun Oommen , Thara Pratap , Sushil Chandi , Muhammed Jasim Abdul Jalal

Parasellar extra-axial cavernomas are rare lesions. The authors report a case of extra-axial cavernoma in a 50-year-old male patient, who presented with occipital headache and double vision. The magnetic resonance imaging showed an enhancing extra-axial dural-based mass in the left parasellar... Read more

Parasellar extra-axial cavernomas are rare lesions. The authors report a case of extra-axial cavernoma in a 50-year-old male patient, who presented with occipital headache and double vision. The magnetic resonance imaging showed an enhancing extra-axial dural-based mass in the left parasellar region invading cavernous sinus, hyper-intense on T2-weighted images, iso-intense on T1-weighted images and high relative cerebral blood velocity on magnetic resonance perfusion. The patient underwent a left pterional craniotomy and parasellar space occupying lesion was excised. Histopathology was suggestive of cavernous hemangioma. Back

Neuroimmunol Neuroinflammation 2017;4:16-9. | doi:10.20517/2347-8659.2016.49 HTML PDF

Topic: Infectious Disease of Central Nervous System| Open Access

Current diagnosis and treatment of cryptococcal meningitis without acquired immunodeficiency syndrome

Xiao-Su Guo , Hui Bu , Jun-Ying He , Yue-Li Zou , Yue Zhao , Yuan-Yuan Li , Jun-Zhao Cui , Ming-Ming Zheng , Wei-Xin Han , Ze-Yan Zhao

Cryptococcal meningitis (CM) is a central nervous system infectious disease caused by Cryptococcus. It is the most common fungal infection in the central nervous system, accounting for about 48% of fungal infection. The disease occurs mainly in acquired immunodeficiency syndrome (AIDS) patients... Read more

Cryptococcal meningitis (CM) is a central nervous system infectious disease caused by Cryptococcus. It is the most common fungal infection in the central nervous system, accounting for about 48% of fungal infection. The disease occurs mainly in acquired immunodeficiency syndrome (AIDS) patients and concentrates in the immunocompromised people without AIDS. There are nearly one million new cases of CM each year, and about 70% of them died. In China, CM occurs mainly in people without AIDS and there is an increasing trend in recent years. Early diagnosis and treatment is the key to reducing morbidity and mortality associated with CM. The diagnosis mainly depends on laboratory examination such as morphological examination, fungal culture and antigen detection. History, clinical manifestation and imaging examination are the important parts of auxiliary examination. The initial combined antifungal treatment is emphasized, and the principle of fractional treatment including induction, consolidation and maintenance therapy should be followed. The high intracranial pressure must be reduced actively at the same time. In addition, it is proved that the novel immunotherapy combined with antifungal agents can improve the curative effect and limit the chance of antimicrobial resistance. Large-scale clinical trials are needed for further study. Back

Neuroimmunol Neuroinflammation 2016;3:249-56. | doi:10.20517/2347-8659.2016.10 HTML PDF

Topic: Autoimmune neurological diseases associated with autoantibodies specific for synaptic antigens| Open Access

Neurological diseases associated with autoantibodies targeting the voltage-gated potassium channel complex: immunobiology and clinical characteristics

Domenico Plantone , Rosaria Renna , Tatiana Koudriavtseva

Voltage-gated potassium channels (VGKCs) represent a group of tetrameric signaling proteins with several functions, including modulation of neuronal excitability and neurotransmitter release. Moreover, VGKCs give a key contribution to the generation of the action potential. VGKCs are complexed... Read more

Voltage-gated potassium channels (VGKCs) represent a group of tetrameric signaling proteins with several functions, including modulation of neuronal excitability and neurotransmitter release. Moreover, VGKCs give a key contribution to the generation of the action potential. VGKCs are complexed with other neuronal proteins, and it is now widely known that serum autoantibodies directed against VGKCs are actually directed against the potassium channel subunits only in a minority of patients. By contrast, these autoantibodies more commonly target three proteins that are complexed with alpha-dendrotoxin-labeled potassium channels in brain extracts. These three proteins are contactin-associated protein-2 (Caspr-2), leucine-rich, glioma inactivated 1 (LGI-1) protein and the protein Tag-1/contactin-2. Neoplasms are detected only in a minority of seropositive patients for VGKC complex-IgG and do not significantly associate with Caspr-2 or LGI-1. Among all the cancers described in association with VGKC complex-IgG, lung carcinoma, thymoma, and hematologic malignancies are the most commonly detected. We will review all the major neurological conditions associated with VGKC complex-IgG. These include Isaacs' syndrome, Morvan syndrome, limbic encephalitis, facio-brachial dystonic seizures, chorea and other movement disorders, epilepsy, psychosis, gastrointestinal neuromuscular diseases, a subacute encephalopathy that mimics Creutzfeldt-Jakob prion disease both clinically and radiologically and autoimmune chronic pain. The vast majority of these conditions are reversible by immunotherapy, and it is becoming increasingly recognized that early diagnosis and detection of VGKC complex-IgG is critical in order to rapidly start the treatment. As a result, VGKC complex-IgG are now part of the investigation of patients with unexplained subacute onset of epilepsy, memory or cognitive problems, or peripheral nerve hyperexcitability syndromes. Back

Neuroimmunol Neuroinflammation 2016;3:69-78. | doi:10.4103/2347-8659.169883 HTML PDF

Review| Open Access

Neurological manifestations in Fabry disease

Joseph Bruno Bidin Brooks , Yara Dadalti Fragoso

Fabry disease (FD) is a rare, progressive, multisystem and highly debilitating disease. FD is an X-linked lysosome storage disorder that results in α-galactosidase A deficiency. The subsequent accumulation of glycosphingolipids is more evident in vascular endothelium and smooth-muscle cells. The... Read more

Fabry disease (FD) is a rare, progressive, multisystem and highly debilitating disease. FD is an X-linked lysosome storage disorder that results in α-galactosidase A deficiency. The subsequent accumulation of glycosphingolipids is more evident in vascular endothelium and smooth-muscle cells. The resulting effect of the deposition is generalized inflammation and vasculopathy, which can also affect the central and peripheral nervous system. FD progresses with kidney dysfunction, angiokeratoma of the skin, cardiomyopathy, cerebrovascular events and neurological disorders. In the present review, the neurological manifestations of FD are summarized with emphasis on cerebral vasculopathy, cochlear nerve dysfunction, psychiatric and cognitive symptoms, autonomic dysfunction and peripheral neuropathy. Enzyme replacement therapy is also discussed in the light of its more prominent effects when administered early in life, which make it essential to diagnose FD as soon as possible. Back

Neuroimmunol Neuroinflammation 2016;3:228-31. | doi:10.20517/2347-8659.2016.36 HTML PDF

Review| Open Access

Neuronal toll-like receptors and neuro-immunity in Parkinson's disease, Alzheimer's disease and stroke

Carmen D. Rietdijk , Richard J. A. van Wezel , Johan Garssen , Aletta D. Kraneveld

Toll-like receptors (TLRs) are part of the innate immune system important for the initiation of proper immune responses towards microorganisms. Neuronal TLRs are considered to be part of the interactions between the immune system and the nervous system, the major sensing systems in mammals. The... Read more

Toll-like receptors (TLRs) are part of the innate immune system important for the initiation of proper immune responses towards microorganisms. Neuronal TLRs are considered to be part of the interactions between the immune system and the nervous system, the major sensing systems in mammals. The review entitled “Neuronal toll-like receptors and neuro-immunity in Parkinson’s disease, Alzheimer’s disease and stroke” by Rietdijk et al. offers an overview of the current knowledge about (neuronal) TLRs in neurodegenerative pathologies. Back

Neuroimmunol Neuroinflammation 2016;3:27-37. | doi:10.20517/2347-8659.2015.28 HTML PDF

Review| Open Access

Neuroinflammatory modulators of oligodendrogenesis

Ana Armada-Moreira , Filipa F. Ribeiro , Ana M. Sebastião , Sara Xapelli

Oligodendrocytes are key neural cells that are responsible for producing myelin sheaths that wrap around neuronal axons in the central nervous system. Myelin is essential to insulate neurons and maintain a fast and saltatory propagation of action potentials along the axon. However,... Read more

Oligodendrocytes are key neural cells that are responsible for producing myelin sheaths that wrap around neuronal axons in the central nervous system. Myelin is essential to insulate neurons and maintain a fast and saltatory propagation of action potentials along the axon. However, oligodendrocytes are very susceptible to damage, and thus demyelination may arise from a brain lesion or a neurodegenerative disorder. Consequently, demyelination produces a loss of axonal insulation leading to sensory or motor neuron failure. During adulthood, there are two main sources of oligodendrocytes: parenchymal oligodendrocyte precursor cells (OPCs) and subventricular zone derived OPCs. In this review, we will discuss oligodendrogenesis derived from these two sources, and also highlight their main extrinsic and intrinsic modulators. In addition, the neuroinflammatory mediators of oligodendrogenesis will also be assessed. Back

Neuroimmunol Neuroinflammation 2015;2:263-73. | doi:10.4103/2347-8659.167311 HTML PDF

Review| Open Access

Necroptosis: a new link between cell death and inflammation

Yuan-Hang Pan , Xun-Yuan Liu , Jia-Qiang Liu , Qian Liu , Yang Yang , Jia-Lei Yang , Xiu-Fen Zhang , Yin Wu , Ya-Zhou Wang

Necroptosis is a type of newly identified cell death induced by apoptotic stimuli under conditions where apoptotic execution is prevented. Studies over the past 10 years have revealed the molecular mechanism of necroptosis and challenged the old conception that necrosis is un-programmed.... Read more

Necroptosis is a type of newly identified cell death induced by apoptotic stimuli under conditions where apoptotic execution is prevented. Studies over the past 10 years have revealed the molecular mechanism of necroptosis and challenged the old conception that necrosis is un-programmed. Recently, more and more data have emerged suggesting a close association between necroptosis and inflammation. In this review, the authors summarized the current knowledge of the mechanism of necroptosis, focusing on tumour necrosis factor α induced necroptosis and the roles of necroptosis in regulating inflammation. In particular, we discussed the occurrence of necroptosis and its relation with inflammation in neurological diseases hoping to provide new insight for the research and treatment of neuroinflammatory disorders. Back

Neuroimmunol Neuroinflammation 2016;3:156-60. | doi:10.20517/2347-8659.2015.59 HTML PDF

Guidelines| Open Access

China guidelines for the diagnosis and treatment of myasthenia gravis

Zhu-Yi Li

Myasthenia gravis (MG) is a typical autoimmune disease mediated by auto-antibodies, immune cells and complement systems at the postsynaptic membrane of the neuromuscular junction. Over 80 % of MG patients have anti-acetylcholine receptor antibody. This guideline will describe the clinical... Read more

Myasthenia gravis (MG) is a typical autoimmune disease mediated by auto-antibodies, immune cells and complement systems at the postsynaptic membrane of the neuromuscular junction. Over 80 % of MG patients have anti-acetylcholine receptor antibody. This guideline will describe the clinical manifestations and classification, laboratory examinations, diagnosis and differential diagnosis, treatment and prognosis. Back

Neuroimmunol Neuroinflammation 2016;3:1-9. | doi:10.20517/2347-8659.2015.60 HTML PDF

Topic: Autoimmune neurological diseases associated with autoantibodies specific for synaptic antigens| Open Access

Diagnostic algorithms in autoimmune encephalitis

Valentina Damato

Over the past decade the discovery of novel forms of encephalitis associated with neuronal surface antibodies had changed the paradigms for diagnosing and treating disorders that were previously mischaracterized. Recognition of clinical syndromes, consistent methods of diagnosis, and early... Read more

Over the past decade the discovery of novel forms of encephalitis associated with neuronal surface antibodies had changed the paradigms for diagnosing and treating disorders that were previously mischaracterized. Recognition of clinical syndromes, consistent methods of diagnosis, and early targeted immunotherapy can lead to a favorable outcome in diseases that may be associated with significant disability or death if left untreated. Here the conditions associated with neuronal surface antibodies are briefly reviewed, some general aspects of these syndromes are considered and guidelines that could help in the recognition of these disorders are suggested. Furthermore, a diagnostic algorithm to detect and characterize neuronal cell surface autoantibodies is suggested and some of the caveats of serum testing are outlined. Future directions will involve the identification of novel autoantibodies, the standardization of methods to detect and characterize them, as well as evaluation of the most efficacious therapeutic strategies in patients with established diagnosis of autoimmune encephalitis. Back

Neuroimmunol Neuroinflammation 2016;3:93-7. | doi:10.20517/2347-8659.2015.43 HTML PDF

Case Report| Open Access

Disc herniation or ependymoma recurrence?

Aristeidis H. Katsanos , Ioannis Sarmas , Sotirios Giannopoulos , Sigliti-Henrietta Pelidou , Athanassios P. Kyritsis

We present a 41-year-old female with previous history of ependymoma who underwent gross-total resection of the tumor and ventriculo-peritoneal shunt placement, followed by radiotherapy. Three years later a small enhancing area was noted in the left anterolateral spinal cord at the level of the... Read more

We present a 41-year-old female with previous history of ependymoma who underwent gross-total resection of the tumor and ventriculo-peritoneal shunt placement, followed by radiotherapy. Three years later a small enhancing area was noted in the left anterolateral spinal cord at the level of the C1-C2 vertebrae and a left posterior-lateral herniated disk in the C5-C6 level which was not present in the earlier MRI. This is a unique case, in which herniated disk pressuring effects needed to be differentiated from both radiation-induced treatment effect and tumor recurrence. Back

Neuroimmunol Neuroinflammation 2016;3:65-8. | doi:10.20517/2347-8659.2015.42 HTML PDF

Topic: Autoimmune neurological diseases associated with autoantibodies specific for synaptic antigens| Open Access

Autoimmune encephalopathies in children: diagnostic clues and therapeutic challenges

Giorgia Olivieri , Ilaria Contaldo , Gloria Ferrantini , Elisa Musto , Roberta Scalise , Maria Chiara Stefanini , Domenica Battaglia , Eugenio Mercuri

Neuronal surface antibody syndromes (NSAS) encompass a variety of disorders associated with “neuronal surface antibodies”. These share clinical and neuroradiological features that pose challenges related to their recognition and treatment. Recent epidemiological studies show a clear predominance... Read more

Neuronal surface antibody syndromes (NSAS) encompass a variety of disorders associated with “neuronal surface antibodies”. These share clinical and neuroradiological features that pose challenges related to their recognition and treatment. Recent epidemiological studies show a clear predominance for the glutamate-N-methyl-D-aspartate receptor encephalitis in both adults and pediatric population. Despite this, the overall NSAS’s incidence remains underestimated, and diagnosis persists to be not always easy to achieve. Based on current literature data, in this paper the authors propose a diagnostic pathway to approach and treat pediatric NSAS. An autoimmune etiology can be suggested through the integration of clinical, immunological, electrophysiological and neuroradiological data. On that basis, a target treatment can be started, consisting of corticosteroids and intravenous immunoglobulin or plasma exchange as a first-line immunotherapy, followed by second-line drugs including rituximab, cyclophosphamide or mycophenolate mophetil, if the case. In children a prompt diagnosis and a targeted treatment may lead to a better clinical outcome. Nevertheless further studies are required to assess the need of more tailored treatments according to long-term outcome findings and prognostic factors in different NSAS. Back

Neuroimmunol Neuroinflammation 2016;3:147-55. | doi:10.20517/2347-8659.2016.09 HTML PDF

Original Article| Open Access

Detection of Epstein-Barr virus infection subtype in patients with multiple sclerosis by indirect immunofluorescence assay

Shan-Chao Zhang , Lei Liu , Rui-Jin Wang , Hou-Zhen Tuo , Yan-Jun Guo , Li Yi , De-Xin Wang , Jia-Wei Wang

Aim: The aim was to investigate the infectious conditions of Epstein-Barr virus (EBV) in patients with multiple sclerosis (MS). Methods: Cerebrospinal fluid (CSF) of 20 patients with MS and 20 with other neurological diseases (OND) were tested with indirect immunofluorescence for anti-EBV capsid... Read more

Aim: The aim was to investigate the infectious conditions of Epstein-Barr virus (EBV) in patients with multiple sclerosis (MS). Methods: Cerebrospinal fluid (CSF) of 20 patients with MS and 20 with other neurological diseases (OND) were tested with indirect immunofluorescence for anti-EBV capsid antigen (EBV-CA) immunoglobulin G (IgG), IgG affinity for anti-EBV-CA, anti-EBV-CA immunoglobulin M (IgM), anti-EBV early antigen (EBV-EA) IgG and anti-EBV nuclear antigen (EBNA) IgG. According to the pattern of antibodies in CSF, infection rates of acute, chronic, primary, recurrent, and past infections were analyzed in the two groups of patients. Results: There were no significant differences in anti-EBV-CA, anti-EBC-EA, and anti-EBNA antigen IgG in CSF between MS and OND patients (P > 0.05). The positive rate of low affinity for anti-EBV-CA IgG in MS patients was significantly higher than that for OND patients (75% vs. 40%, P < 0.05). Furthermore, significant differences in the positive rate of anti-EBV-CA IgM were found between MS and OND patients (70% vs. 25%, P<0.05). Of the MS patients, 75% were in an EBV acute infection state compared with 40% of OND patients (P < 0.05). Conclusion: Acute infection of EBV closely correlates with the occurrence of MS. Back

Neuroimmunol Neuroinflammation 2014;1:24-8. | doi:10.4103/2347-8659.135572 HTML PDF

Case Report| Open Access

Isolated palatal palsy: a clinical rarity

Harpreet Singh , Rekha Mathur , Parminder Kaur

Acquired isolated palatal palsy is a rare disease. It is commonly seen in children. It usually presents with acute onset nasal regurgitation of fluids, rhinolalia, and palatal asymmetry. Many causes of this disease, such as infections, trauma, tumor, and brainstem lesions, etc., have been... Read more

Acquired isolated palatal palsy is a rare disease. It is commonly seen in children. It usually presents with acute onset nasal regurgitation of fluids, rhinolalia, and palatal asymmetry. Many causes of this disease, such as infections, trauma, tumor, and brainstem lesions, etc., have been reported. However, the most plausible explanation is immunological/ischemic damage to the affected nerve. After ruling out major potential causes of this disease, the damage is often considered to be idiopathic in nature. This disease has a benign self‑limiting course with excellent recovery. In accordance with a hypothesized immunological basis for this condition, treatment with steroids results in significant improvement in its clinical features. Back

Neuroimmunol Neuroinflammation 2015;2:190-2. | doi:10.4103/2347-8659.153981 HTML PDF

Review| Open Access

Current overview of myasthenia gravis and experience in China

Jun Guo , Dan Dang , Hong-Zeng Li , Zhu-Yi Li

Myasthenia gravis (MG) is an acquired autoimmune disease affecting synaptic transmission via the neuromuscular junction mainly due to the presence of auto-antibodies targeting acetylcholine receptors. Ocular or generalized MG is clinically diagnosed when the extra-ocular muscles or other muscle... Read more

Myasthenia gravis (MG) is an acquired autoimmune disease affecting synaptic transmission via the neuromuscular junction mainly due to the presence of auto-antibodies targeting acetylcholine receptors. Ocular or generalized MG is clinically diagnosed when the extra-ocular muscles or other muscle groups beyond the extra-ocular muscles are involved. MG occurs in both sexes at any ages from all races but shows a wide variability in incidence and prevalence. Differences in clinical phenotypes of MG patients between West and East countries have been observed. Herein, we review the current concept on epidemiology, classification, and generalized progression in MG, mainly focusing on the differential features from mainland China. Back

Neuroimmunol Neuroinflammation 2014;1:127-30. | doi:10.4103/2347-8659.143664 HTML PDF

Editorial| Open Access

On the need to unify neuroscience and physics

Maurits van den Noort , Sabina Lim , Peggy Bosch Neuroimmunol Neuroinflammation 2016;3:271-3. | doi:10.20517/2347-8659.2016.55 HTML PDF

Topic: Autoimmune neurological diseases associated with autoantibodies specific for synaptic antigens| Open Access

Diagnostic algorithms in autoimmune encephalitis

Valentina Damato

Over the past decade the discovery of novel forms of encephalitis associated with neuronal surface antibodies had changed the paradigms for diagnosing and treating disorders that were previously mischaracterized. Recognition of clinical syndromes, consistent methods of diagnosis, and early... Read more

Over the past decade the discovery of novel forms of encephalitis associated with neuronal surface antibodies had changed the paradigms for diagnosing and treating disorders that were previously mischaracterized. Recognition of clinical syndromes, consistent methods of diagnosis, and early targeted immunotherapy can lead to a favorable outcome in diseases that may be associated with significant disability or death if left untreated. Here the conditions associated with neuronal surface antibodies are briefly reviewed, some general aspects of these syndromes are considered and guidelines that could help in the recognition of these disorders are suggested. Furthermore, a diagnostic algorithm to detect and characterize neuronal cell surface autoantibodies is suggested and some of the caveats of serum testing are outlined. Future directions will involve the identification of novel autoantibodies, the standardization of methods to detect and characterize them, as well as evaluation of the most efficacious therapeutic strategies in patients with established diagnosis of autoimmune encephalitis. Back

Neuroimmunol Neuroinflammation 2016;3:93-7. | doi:10.20517/2347-8659.2015.43 HTML PDF

Review| Open Access

Chronic inflammation drives glioma growth: cellular and molecular factors responsible for an immunosuppressive microenvironment

Edward T Ha , Joseph P Antonios , Horacio Soto , Robert M Prins , Isaac Yang , Noriyuki Kasahara , Linda M Liau , Carol A Kruse

This review examines glioma disease initiation, promotion, and progression with a focus on the cell types present within the tumor mass and the molecules responsible for the immunosuppressive microenvironment that are present at each step of the disease. The cell types and molecules present also... Read more

This review examines glioma disease initiation, promotion, and progression with a focus on the cell types present within the tumor mass and the molecules responsible for the immunosuppressive microenvironment that are present at each step of the disease. The cell types and molecules present also correlate with the grade of malignancy. An overall "type 2" chronic inflammatory microenvironment develops that facilitates glioma promotion and contributes to the neo-vascularization characteristic of gliomas. An immunosuppressive microenvironment shields the tumor mass from clearance by the patient's own immune system. Here, we provide suggestions to deal with a chronically-inflamed tumor microenvironment and provide recommendations to help optimize adjuvant immune- and gene therapies currently offered to glioma patients. Back

Neuroimmunol Neuroinflammation 2014;1:66-76. | doi:10.4103/2347-8659.139717 HTML PDF

Topic: Autoimmune neurological diseases associated with autoantibodies specific for synaptic antigens| Open Access

Autoimmune encephalopathies in children: diagnostic clues and therapeutic challenges

Giorgia Olivieri , Ilaria Contaldo , Gloria Ferrantini , Elisa Musto , Roberta Scalise , Maria Chiara Stefanini , Domenica Battaglia , Eugenio Mercuri

Neuronal surface antibody syndromes (NSAS) encompass a variety of disorders associated with “neuronal surface antibodies”. These share clinical and neuroradiological features that pose challenges related to their recognition and treatment. Recent epidemiological studies show a clear predominance... Read more

Neuronal surface antibody syndromes (NSAS) encompass a variety of disorders associated with “neuronal surface antibodies”. These share clinical and neuroradiological features that pose challenges related to their recognition and treatment. Recent epidemiological studies show a clear predominance for the glutamate-N-methyl-D-aspartate receptor encephalitis in both adults and pediatric population. Despite this, the overall NSAS’s incidence remains underestimated, and diagnosis persists to be not always easy to achieve. Based on current literature data, in this paper the authors propose a diagnostic pathway to approach and treat pediatric NSAS. An autoimmune etiology can be suggested through the integration of clinical, immunological, electrophysiological and neuroradiological data. On that basis, a target treatment can be started, consisting of corticosteroids and intravenous immunoglobulin or plasma exchange as a first-line immunotherapy, followed by second-line drugs including rituximab, cyclophosphamide or mycophenolate mophetil, if the case. In children a prompt diagnosis and a targeted treatment may lead to a better clinical outcome. Nevertheless further studies are required to assess the need of more tailored treatments according to long-term outcome findings and prognostic factors in different NSAS. Back

Neuroimmunol Neuroinflammation 2016;3:147-55. | doi:10.20517/2347-8659.2016.09 HTML PDF

Review| Open Access

Necroptosis: a new link between cell death and inflammation

Yuan-Hang Pan , Xun-Yuan Liu , Jia-Qiang Liu , Qian Liu , Yang Yang , Jia-Lei Yang , Xiu-Fen Zhang , Yin Wu , Ya-Zhou Wang

Necroptosis is a type of newly identified cell death induced by apoptotic stimuli under conditions where apoptotic execution is prevented. Studies over the past 10 years have revealed the molecular mechanism of necroptosis and challenged the old conception that necrosis is un-programmed.... Read more

Necroptosis is a type of newly identified cell death induced by apoptotic stimuli under conditions where apoptotic execution is prevented. Studies over the past 10 years have revealed the molecular mechanism of necroptosis and challenged the old conception that necrosis is un-programmed. Recently, more and more data have emerged suggesting a close association between necroptosis and inflammation. In this review, the authors summarized the current knowledge of the mechanism of necroptosis, focusing on tumour necrosis factor α induced necroptosis and the roles of necroptosis in regulating inflammation. In particular, we discussed the occurrence of necroptosis and its relation with inflammation in neurological diseases hoping to provide new insight for the research and treatment of neuroinflammatory disorders. Back

Neuroimmunol Neuroinflammation 2016;3:156-60. | doi:10.20517/2347-8659.2015.59 HTML PDF

Topic: Autoimmune neurological diseases associated with autoantibodies specific for synaptic antigens| Open Access

Neurological diseases associated with autoantibodies targeting the voltage-gated potassium channel complex: immunobiology and clinical characteristics

Domenico Plantone , Rosaria Renna , Tatiana Koudriavtseva

Voltage-gated potassium channels (VGKCs) represent a group of tetrameric signaling proteins with several functions, including modulation of neuronal excitability and neurotransmitter release. Moreover, VGKCs give a key contribution to the generation of the action potential. VGKCs are complexed... Read more

Voltage-gated potassium channels (VGKCs) represent a group of tetrameric signaling proteins with several functions, including modulation of neuronal excitability and neurotransmitter release. Moreover, VGKCs give a key contribution to the generation of the action potential. VGKCs are complexed with other neuronal proteins, and it is now widely known that serum autoantibodies directed against VGKCs are actually directed against the potassium channel subunits only in a minority of patients. By contrast, these autoantibodies more commonly target three proteins that are complexed with alpha-dendrotoxin-labeled potassium channels in brain extracts. These three proteins are contactin-associated protein-2 (Caspr-2), leucine-rich, glioma inactivated 1 (LGI-1) protein and the protein Tag-1/contactin-2. Neoplasms are detected only in a minority of seropositive patients for VGKC complex-IgG and do not significantly associate with Caspr-2 or LGI-1. Among all the cancers described in association with VGKC complex-IgG, lung carcinoma, thymoma, and hematologic malignancies are the most commonly detected. We will review all the major neurological conditions associated with VGKC complex-IgG. These include Isaacs' syndrome, Morvan syndrome, limbic encephalitis, facio-brachial dystonic seizures, chorea and other movement disorders, epilepsy, psychosis, gastrointestinal neuromuscular diseases, a subacute encephalopathy that mimics Creutzfeldt-Jakob prion disease both clinically and radiologically and autoimmune chronic pain. The vast majority of these conditions are reversible by immunotherapy, and it is becoming increasingly recognized that early diagnosis and detection of VGKC complex-IgG is critical in order to rapidly start the treatment. As a result, VGKC complex-IgG are now part of the investigation of patients with unexplained subacute onset of epilepsy, memory or cognitive problems, or peripheral nerve hyperexcitability syndromes. Back

Neuroimmunol Neuroinflammation 2016;3:69-78. | doi:10.4103/2347-8659.169883 HTML PDF

Review| Open Access

Neuronal toll-like receptors and neuro-immunity in Parkinson's disease, Alzheimer's disease and stroke

Carmen D. Rietdijk , Richard J. A. van Wezel , Johan Garssen , Aletta D. Kraneveld

Toll-like receptors (TLRs) are part of the innate immune system important for the initiation of proper immune responses towards microorganisms. Neuronal TLRs are considered to be part of the interactions between the immune system and the nervous system, the major sensing systems in mammals. The... Read more

Toll-like receptors (TLRs) are part of the innate immune system important for the initiation of proper immune responses towards microorganisms. Neuronal TLRs are considered to be part of the interactions between the immune system and the nervous system, the major sensing systems in mammals. The review entitled “Neuronal toll-like receptors and neuro-immunity in Parkinson’s disease, Alzheimer’s disease and stroke” by Rietdijk et al. offers an overview of the current knowledge about (neuronal) TLRs in neurodegenerative pathologies. Back

Neuroimmunol Neuroinflammation 2016;3:27-37. | doi:10.20517/2347-8659.2015.28 HTML PDF