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

Review| Open Access

Neuroimaging of corpus callosum in central nervous system demyelinating disorders

Masoud Etemadifar , Amir Neshatfar , Amir Arsalan Zamani , Mehri Salari

Corpus callosum (CC) is the largest white matter structure in the brain, consisting of 200-250 million contralateral axonal projections. It is the major commissural pathway connecting the hemispheres of human brain. The pathology of CC includes wide variety of entities that arise from different... Read more

Corpus callosum (CC) is the largest white matter structure in the brain, consisting of 200-250 million contralateral axonal projections. It is the major commissural pathway connecting the hemispheres of human brain. The pathology of CC includes wide variety of entities that arise from different causes such as congenital, inflammatory, tumoral, degenerative, infectious, etc. This study reviews the most reliable neuroimaging data of human CC in central nervous system (CNS) demyelinating diseases to facilitate the understanding of different pathological entities of the CC and their role in anticipation of probable prognostic findings. After a brief description of normal anatomy and functions of CC, this review examines the most valuable findings obtained using conventional and functional magnetic resonance imaging. It also demonstrates the most well organized findings of how CC features influence prognostic factors of demyelinating disorders, which could have a great value for choosing proper therapy methods. The authors also provided a brief review of other demyelinating disorders which are primarily caused by other pathological factors other than autoimmunity. As a conclusion, the authors showed the importance of CC as an critical part of the brain, which should be explored by different methods of imaging, correspondent to clinical evaluation of CNS demyelinating disorder to widen our knowledge on pathology and clinical patterns of such disorders. Back

Neuroimmunol Neuroinflammation 2017;4:69-77. | doi:10.20517/2347-8659.2017.02 +HTML| PDF

Review| Open Access

Interactions between neurotropic pathogens, neuroinflammatory pathways, and autophagic neural cell death

Priyadarshi Soumyaranjan Sahu , Eunice Ter

In recent times, there has been a significant increase in studies focusing on immunological functions of autophagy, however, knowledge of its roles and regulations in the central nervous system remains unclear. Present reviews highlight the molecular cross talk between host cell autophagy with... Read more

In recent times, there has been a significant increase in studies focusing on immunological functions of autophagy, however, knowledge of its roles and regulations in the central nervous system remains unclear. Present reviews highlight the molecular cross talk between host cell autophagy with inflammatory pathways in the context of neuro-infections. Intracellular pathogens might have an ability to manipulate the autophagy regulation process. An augmented autophagy and inflammation at the site of infection is traditionally considered host protective. Moreover, host cell autophagy might also facilitate pathogen survivability and multiplication in the brain environment. Consequently, an excessive autophagy and neuroinflammatory process do put surrounding healthy brain tissue at risk of pathogen invasion. The question arises, whether there are any known direct interactions of intracellular neurotropic pathogens with this degradative pathway that favour intracerebral pathogen survival and growth? It is worth exploring any such cooperation between pathogen factors and altered immune pathways that modulate autophagy regulatory genes causing massive neuronal damage. A detailed understanding of molecular mechanisms in microbial pathogenesis, neuroinflammatory and neuronal autophagy pathways might identify novel therapeutic targets and diagnostic biomarkers. Back

Neuroimmunol Neuroinflammation 2018;5:2. | doi:10.20517/2347-8659.2017.43 +HTML| PDF

Case Report| Open Access

Steroids and plasma exchange in Isaacs' syndrome with anti-Caspr2 antibodies

Daniele Orsucci , Gianfranco Cafforio , Gianluca Moscato , Alessandro Napolitano , Marco Margelli , Monica Mazzoni

Isaacs’ syndrome is a disease characterized by nerve hyperexcitability. The patients are commonly treated with symptomatic therapies and immunomodulatory approaches, but no clinical trials are available to date. Here, we report the case of an anti-Caspr2-positive patient, presenting with... Read more

Isaacs’ syndrome is a disease characterized by nerve hyperexcitability. The patients are commonly treated with symptomatic therapies and immunomodulatory approaches, but no clinical trials are available to date. Here, we report the case of an anti-Caspr2-positive patient, presenting with continuous muscle twitches and diffuse muscle pain. He experienced a nearly complete clinical response to intravenous high-dose steroids combined with plasma exchange, sustained for at least 1 year. Our experience suggests that methylprednisolone 1000 mg/day × 5 days and consecutive tapering followed by plasma exchange may be efficient and well tolerated in patient with Isaacs’ syndrome due to anti-Caspr2 antibodies. Back

Neuroimmunol Neuroinflammation 2018;5:7. | doi:10.20517/2347-8659.2017.67 +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

Original Article| Open Access

Peripheral NK and B regulatory cell frequencies are altered with symptomatic exacerbation in generalized myasthenia gravis patients

Xiao-Yin Lai , Meng-Cui Gui , Jing Lin , Yue Li , Xuan Luo , Long-Xuan Li , Bi-Tao Bu

Aim: Myasthenia gravis (MG) is an autoimmune disease, in which immunotherapy can improve symptoms for a period, but the majority of patients still experience symptomatic fluctuation or develop myasthenic crisis. This study aimed to explore the relationship between frequency of peripheral... Read more

Aim: Myasthenia gravis (MG) is an autoimmune disease, in which immunotherapy can improve symptoms for a period, but the majority of patients still experience symptomatic fluctuation or develop myasthenic crisis. This study aimed to explore the relationship between frequency of peripheral lymphocyte subsets and myasthenia gravis disease stage. Methods: The percentages of B regulatory (Breg) cells and natural killer (NK) cells in the peripheral blood samples obtained from 54 MG patients and 10 healthy controls were surveyed using flow cytometry. MG patients were subdivided into the ocular MG, generalized MG (GMG) in exacerbation stage and GMG in remission stage. Results: The percentage of Breg cells was significantly decreased in both the exacerbation stage (6.93 ± 1.18) and remission stage (6.56 ± 1.32) of GMG patients compared to healthy controls (15.97 ± 2.88). The percentage of NK cells were significantly increased in GMG patients in remission stage (20.69 ± 3.45) compared to healthy controls (11.33 ± 0.95). Frequency of NK cells in the patients in remission stage was significantly increased compared to patients in exacerbation (20.69 ± 3.45 vs. 12.32 ± 1.42). Conclusion: The Breg cells are involved in the pathogenesis of GMG, and NK cells are closely associated with the fluctuation of MG symptoms. NK cells could be a useful marker for MG activity and for monitoring effectiveness of immunotherapy. Back

Neuroimmunol Neuroinflammation 2017;4:179-87. | doi:10.20517/2347-8659.2017.29 +HTML| PDF

Original Article| Open Access

Neuroprotection by minocycline in murine traumatic spinal cord injury: analyses of matrix metalloproteinases

Tiffany Rice , Jennifer E.A. Larsen , Hui Li , Robert K. Nuttall , Peter H. Larsen , Steven Casha , John Hurlbert , Dylan R. Edwards , V. Wee Yong

Aim: Minocycline has neuroprotective activities in several models of neurological disorders including spinal cord injury (SCI) where it prevents axonal loss and improves functional recovery. There are still gaps of knowledge on minocycline in SCI including whether it ameliorates neuronal loss at... Read more

Aim: Minocycline has neuroprotective activities in several models of neurological disorders including spinal cord injury (SCI) where it prevents axonal loss and improves functional recovery. There are still gaps of knowledge on minocycline in SCI including whether it ameliorates neuronal loss at the focal site of trauma, and whether minocycline reduces the activity of matrix metalloproteinases (MMPs), a family of enzymes implicated in the pathophysiology of SCI. This study addressed these gaps. Methods: Mice were treated with either minocycline or vehicle control after a spinal cord contusion. MMPs were compared between the two groups using real time polymerase chain reaction and zymography. Immunohistochemistry was used to examine microglial activation and neuronal cell death. Results: While several MMP members were elevated in the spinal cord following injury, treatment with minocycline did not affect their expression. Importantly, minocycline reduced the loss of neurons in the epicenter of damage to the spinal cord and in segments caudal and rostral to the injury. Conclusion: Despite the inability of minocycline to alter MMPs, the results of neuroprotection at the lesion site support the continued testing of minocycline as a neuroprotective medication in experimental and clinical SCI. Back

Neuroimmunol Neuroinflammation 2017;4:243-53. | doi:10.20517/2347-8659.2017.51 +HTML| PDF

Case Report| Open Access

A rare case of quadrigeminal plate lipoma presenting with the sixth cranial nerve palsy

Bipin Kumar Chaurasia , Narendra Shalike , Silak Ram Chaudhary , Shamsul Alam , Dhiman Chowdhory , Kanak Kanti Barua , Ranjit Kumar Chaurasiya , Raushan Kumar Chaurasia , Ramesh Kumar Chaurasia , Tolga Dundar

Intracranial lipomas are rare benign tumour that is slow growing, generally asymptomatic, most frequently located in the midline areas and are usually an incidental finding on imaging and therefore cases are not frequently reported. This study reports a case of a patient with quadrigeminal plate... Read more

Intracranial lipomas are rare benign tumour that is slow growing, generally asymptomatic, most frequently located in the midline areas and are usually an incidental finding on imaging and therefore cases are not frequently reported. This study reports a case of a patient with quadrigeminal plate lipoma presenting with obstructive hydrocephalous and the 6th cranial nerve palsy that was successfully treated with ventriculo-peritoneal shunting without addressing the lesion. Back

Neuroimmunol Neuroinflammation 2017;4:232-5. | doi:10.20517/2347-8659.2017.40 +HTML| PDF

Topic: Stroke| Open Access

When friend turns foe: central and peripheral neuroinflammation in central nervous system injury

Paul Marcet , Nicole Santos , Cesar V. Borlongan

Injury to the central nervous system (CNS) is common, and though it has been well studied, many aspects of traumatic brain injury (TBI) and stroke are poorly understood. TBI and stroke are two pathologic events that can cause severe, immediate impact to the neurostructure and function of the CNS,... Read more

Injury to the central nervous system (CNS) is common, and though it has been well studied, many aspects of traumatic brain injury (TBI) and stroke are poorly understood. TBI and stroke are two pathologic events that can cause severe, immediate impact to the neurostructure and function of the CNS, which has been recognized recently to be exacerbated by the body’s own immune response. Although the brain damage induced by the initial trauma is most likely unsalvageable, the secondary immunologic deterioration of neural tissue gives ample opportunity for therapeutic strategists seeking to mitigate TBI’s secondary detrimental effects. The purpose of this paper is to highlight the cell death mechanisms associated with CNS injury with special emphasis on inflammation. The authors discuss sources of inflammation, and introduce the role of the spleen in the systemic response to inflammation after CNS injury. Back

Neuroimmunol Neuroinflammation 2017;4:82-92. | doi:10.20517/2347-8659.2017.07 +HTML| PDF

Original Article| Open Access

Analysis of clinical data of viral encephalitis patients complicated with epilepsy during the acute phase

Shi-Ying Chen , Wei Ma , Yan-Yan Chen , Xue-Wen Fan

Aim: To compare the difference between viral encephalitis patients complicated with epilepsy group and those without epilepsy. Methods: The authors retrospectively study 116 cases of viral encephalitis patients admitted to the General Hospital of Ningxia Medical University and the... Read more

Aim: To compare the difference between viral encephalitis patients complicated with epilepsy group and those without epilepsy. Methods: The authors retrospectively study 116 cases of viral encephalitis patients admitted to the General Hospital of Ningxia Medical University and the Cardia-Cerebrovascular Disease Hospital of Ningxia Medical University from January 2011 to December 2016. There were 39 cases with epilepsy and 77 cases without epilepsy. By surveying the Hospital Information System, the authors collected their clinical data including general situations, medical history, physical examination, clinical presentation, laboratory examination, cerebrospinal fluid examination, imaging examination, electroencephalogram examination (EEG), treatment, and discharge conditions. The authors used SPSS for further analysis and statistics. Results: Medical history: there were significant differences between the two groups in disturbance of consciousness, cognitive dysfunction, and admission conditions (P < 0.05). No significant differences were found in other clinical manifestations. Auxiliary examination: in cerebrospinal fluid (CSF) examination, the patients with epilepsy had higher glucose (P < 0.05). Brain imaging examination shows that cortical involvements in patients with epilepsy were higher (P < 0.05), and EEG examination showed that patients with epilepsy were more severe (P < 0.05). No significant differences were found in other auxiliary examination. Treatment and prognosis: all the patients were given antiviral treatment. Twenty-eight cases of the patients with epilepsy (71.79%) are used of antiepileptic drugs. The prognosis of patients with epilepsy was poor (P < 0.05). Conclusion: Viral encephalitis frequently manifests with seizures in its acute phase, and the incidence of seizures in our study was 33.62%. The main form was generalized seizures (64.10%), which could occur at any age; patients with epilepsy had a higher cortical involvement on imaging and a higher degree of EEG abnormalities than patients without; patients with epilepsy had a higher level of glucose in the CSF; an episode of viral encephalitis complicated with seizures could aggravate disturbances of consciousness and cognitive impairment. The prognosis of patients with epilepsy was poor. Back

Neuroimmunol Neuroinflammation 2017;4:124-31. | doi:10.20517/2347-8659.2017.17 +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

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

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

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

Case Report| Open Access

Progressive muscle cramps with pain as atypical initial presentations of amyotrophic lateral sclerosis: a case report

Cheng-Hui Liu , Chi Zhu , Fan Zeng , Heng Yang , Yan-Jiang Wang

Amyotrophic lateral sclerosis (ALS) is the most common form of motor neuron disease and is a progressive and devastating neurodegenerative disease that affects both lower and upper motor neurons. Muscle cramps, which are characterized by a sudden, painful, involuntary contraction of muscles, are... Read more

Amyotrophic lateral sclerosis (ALS) is the most common form of motor neuron disease and is a progressive and devastating neurodegenerative disease that affects both lower and upper motor neurons. Muscle cramps, which are characterized by a sudden, painful, involuntary contraction of muscles, are not rare in ALS patients. However, muscle cramps do not normally present early in ALS and therefore not used for the initial diagnosis of ALS. In this paper the authors present a case of ALS with initial manifestation of progressive painful muscle cramps in the absence of muscle weakness. This case might help people to recognize atypical foremost presentations of ALS and therefore formulate effective therapies. Back

Neuroimmunol Neuroinflammation 2016;3:170-2. | doi:10.20517/2347-8659.2015.49 +HTML| PDF

Short Communication| Open Access

Trends in neurology fellowship training

Jordan S.A. Williams , Trent S. Hodgson , Fernando D. Goldenberg , Rimas V. Lukas

Aim: A need for Neurologists exists in the US. The majority of Neurology residency graduates go on to additional subspecialty training. Methods: Data from the Accreditation Council for Graduate Medical Education from 2001-2014 and the United Council for Neurologic Subspecialties from was analyzed... Read more

Aim: A need for Neurologists exists in the US. The majority of Neurology residency graduates go on to additional subspecialty training. Methods: Data from the Accreditation Council for Graduate Medical Education from 2001-2014 and the United Council for Neurologic Subspecialties from was analyzed for trends in the number of Neurology subspecialty training programs and their composition. Results: There has been an overall trend of growth in the number of accredited Neurology subspecialty training programs and fellows. These trends vary between specific subspecialties. Conclusion: The authors provide an overview of the contemporary state of Neurology subspecialty training in the US. A clearer understanding of subspecialty training allows for anticipation of workforce surpluses and deficits. Back

Neuroimmunol Neuroinflammation 2017;4:65-8. | doi:10.20517/2347-8659.2017.11 +HTML| PDF

Case Report| Open Access

Differentiation of radiation necrosis from glioblastoma recurrence after radiotherapy

Chrissa Sioka , Anastasia Zikou , Anna Goussia , Spyridon Tsiouris , Loucas G. Astrakas , Athanassios P. Kyritsis

The standard treatment of glioblastoma, the most common type of primary-brain-tumor, involves radiotherapy with concomitant temozolomide chemotherapy. A patient with glioblastoma, post radiotherapy developed magnatic resonance imaging (MRI) changes consistent with either radiation-induced tumor... Read more

The standard treatment of glioblastoma, the most common type of primary-brain-tumor, involves radiotherapy with concomitant temozolomide chemotherapy. A patient with glioblastoma, post radiotherapy developed magnatic resonance imaging (MRI) changes consistent with either radiation-induced tumor necrosis or tumor recurrence. Perfusion MRI was suggestive of radiation necrosis, but magnetic resonance spectroscopy and 99mTc-Tetrofosmin single photon emission computed tomography was indicative of tumor recurrence. Positron emission tomography scan was not available. Tumor recurrence was documented by biopsy. Several advanced imaging methods are available to differentiate tumor recurrence from radiation necrosis in glioblastoma patients. However, in inconclusive cases, brain biopsy should be performed for definite diagnosis. Back

Neuroimmunol Neuroinflammation 2016;3:161-4. | doi:10.20517/2347-8659.2016.08 +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

Original Article| Open Access

Symptom severity, quality of sleep, and treatment adherence among patients suffering from schizophrenia and depression

Peggy Bosch , Janina Waberg , Maurits van den Noort , Heike Staudte , Sabina Lim , Jos Egger

Aim: Treatment non-adherence is a common problem in patients suffering from schizophrenia and depression. This study investigated the possible relationships between symptom severity, quality of sleep, and treatment adherence. Methods: Thirty outpatients with schizophrenia and 58 outpatients with... Read more

Aim: Treatment non-adherence is a common problem in patients suffering from schizophrenia and depression. This study investigated the possible relationships between symptom severity, quality of sleep, and treatment adherence. Methods: Thirty outpatients with schizophrenia and 58 outpatients with depression were enrolled in this study. The beck depression Inventory-II, the positive and negative syndrome scale, and the pittsburgh sleep quality index were used to assess symptom severity and quality of sleep, and sleep log data were used to measure treatment adherence. Results: The preliminary results showed no significant relationship between symptom severity and treatment adherence or between quality of sleep and treatment adherence in patients with depression. However, a significant positive relationship was found between negative symptoms and treatment adherence and a significant negative relationship between quality of sleep and treatment adherence in patients with schizophrenia. Conclusion: The present exploratory study revealed a positive relationship between symptom severity and treatment adherence and a negative relationship between quality of sleep and treatment adherence in patients with schizophrenia, but no significant relationships in patients with depression were found. Future studies are needed in order to gain a better understanding of possible risk factors related to treatment non-adherence Back

Neuroimmunol Neuroinflammation 2016;3:109-16. | doi:10.20517/2347-8659.2015.54 +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

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

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

Original Article| Open Access

A novel method for evaluating microglial activation using ionized calcium-binding adaptor protein-1 staining: cell body to cell size ratio

Iris Bertha Hovens , Csaba Nyakas , Regien Geertruida Schoemaker

Aim: The aim was to validate a newly developed methodology of semi-automatic image analysis to analyze microglial morphology as marker for microglial activation in ionized calcium-binding adaptor protein-1 (IBA-1) stained brain sections. Methods: The novel method was compared to currently used... Read more

Aim: The aim was to validate a newly developed methodology of semi-automatic image analysis to analyze microglial morphology as marker for microglial activation in ionized calcium-binding adaptor protein-1 (IBA-1) stained brain sections. Methods: The novel method was compared to currently used analysis methods, visual characterization of activation stage and optical density measurement, in brain sections of young and aged rats that had undergone surgery or remained naοve. Results: The cell body to cell size ratio of microglia was strongly correlated to the visual characterization activation stage. In addition, we observed specific surgery and age-related changes in cell body size, size of the dendritic processes and cell body to cell size ratio. Conclusion: The novel analysis method provides a sensitive marker for microglial activation in the rat brain, which is quick and easy to perform and provides additional information about microglial morphology. Back

Neuroimmunol Neuroinflammation 2014;1:82-8. | doi:10.4103/2347-8659.139719 +HTML| PDF

Case Report| Open Access

Toluene-induced leukoencephalopathy with characteristic magnetic resonance imaging findings

Fan Zeng , Heng Yang , Hua-Dong Zhou , Yan-Jiang Wang

Toluene-induced leukoencephalopathy is a frequently seen medical condition worldwide; however the lack of specific clinical manifestations and laboratory tests makes it difficult to diagnose. Neuroimaging and medical history are often crucial to diagnosis of this disorder. In this report, a case... Read more

Toluene-induced leukoencephalopathy is a frequently seen medical condition worldwide; however the lack of specific clinical manifestations and laboratory tests makes it difficult to diagnose. Neuroimaging and medical history are often crucial to diagnosis of this disorder. In this report, a case is presented of a patient suffering from toluene-induced leukoencephalopathy with deteriorating cognition impairment and characteristic magnetic resonance imaging (MRI) findings, typified by a "sunflower-like" change in T2-weighted imaging. In addition, the pharmacokinetic properties of toluene are reviewed, as well as the clinical manifestations, typical MRI findings, neuropathology, possible mechanism, and treatment of toluene-induced leukoencephalopathy. Back

Neuroimmunol Neuroinflammation 2014;1:92-4. | doi:10.4103/2347-8659.139721 +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