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Introduction: Alzheimer’s disease (AD) is one of the most prevalent neurodegenerative disorders, characterized by progressive memory loss and cognitive decline, ultimately leading to dementia. Currently, there is no definitive cure, and available treatments focus only on alleviating symptoms and slowing disease progression. In recent years, nanomedicine has been proposed as a potential approach for the treatment of various diseases, including AD. Nanotechnology offers novel solutions to key challenges in AD treatment, such as poor drug solubility in biological fluids, low bioavailability, limited ability to cross the blood-brain barrier (BBB), and rapid drug metabolism. This systematic review describes the potential applications and benefits of nanoparticles in the fight against AD. Materials and Methods: To achieve the study’s objectives, a comprehensive literature search was conducted across reputable databases, covering publications from 1990 to November 2024. The search included keywords related to AD, its diagnosis, and treatment. Results: The findings suggest that nanoparticles can enhance the effectiveness of existing AD treatments by improving drug solubility, increasing bioavailability, and facilitating drug transport across the BBB. These properties suggest that nanoparticles could be promising tools for more effective AD management. Conclusion: Advances in nanomedicine offer significant opportunities for the development of innovative therapeutic approaches for AD. By improving drug delivery and treatment efficacy, nanoparticles could contribute to early detection, better disease management.
 

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Introduction: Cancers are among the most common causes of deaths worldwide and just the third cause of deaths as well as they are more common in elderly, with an aging population in Iran. Iran is going to face an increase in the incidence of malignancies in the next decades. Materials & Methods: This study has tried to use the existing evidences through a systematic review beside the national cancer registry (NCR) database between 2000 and 2009 to find out the incidence of primary malignant and benign CNS tumors in Iran. International databases of Medline, Embase, ISI web of knowledge and Google scholar along with three major Persian indexing websites of SID, MagIran and IranMedex are searched. Primary searches resulted in finding of 966 papers of which 11 were selected for analysis. Results: Primary malignant CNS tumors form 2.3% of all tumors in the ten-year registry data. Incidence of primary malignant brain tumors in Iran is 3.3 per 100,000 person-year, 3.9 for males and 2.8 for females. A total number of 10,797 cases are registered in the NCR data, which demonstrate astrocytoma (32.4%), glioblastoma (29%), oligodendroglioma (6.2%), medulloblastoma (6.1%), and ependymoma (2.7%) as the most common pathologies in primary brain tumors. Primary malignant spinal cord tumors consists 6.8% of all CNS tumors. Common pathologies in spinal cord tumors are malignant neoplasm, ependymoma, astrocytoma and lymphoma. However, the two benign spinal cord tumors of neurofibroma and schwannoma are believed to be more frequent than malignant ones. Conclusion: Most common benign pathologies are meningioma (27.8%), pituitary adenoma (11.3%), schwannoma (5.8%), and congenital tumors (2.4%). Primary benign tumors in Iran have an incidence of 3.5 per 100,000 person-year.

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Introduction: Spreading depression (SD) is a pathophysiological phenomenon, which induced as consequence of ischemia, cerebral hemorrhage and cerebral injury. SD roles in some clinical disorders, including migraine aura, epilepsy, head injury and transient global amnesia, have been documented. SD is a neural hyperactivity, which slowly spread in the brain, passed through neurons or astrocyte, change blood volume, cell metabolism and distribute cell ionic balance. SD is accompanied by a transient hyperactivity, which continues by neuronal depression and hyperexcitability. Conclusion: Various investigation on animal and human brains showed enhancement in NMDA, AMPA, GABA as well as serotonin after SD. This review focuses on wide range of investigation on excitatory and inhibitory neurotransmitters after SD.

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Cell replacement therapy has provided the basis for future clinical applications to treat central nervous system injuries fallowing by car accidents. Induced functional neurons are an option for replacing the lost neurons. The ability to monitor changes in membrane potential is a useful tool for studying neuronal function, but there are only limited options available at present. Here, investigated the potential of voltage-sensitive dyes, RH 795, for imaging the membrane potential of motoneurons like cells (MNLCs) differentiated from adipose derived stem cells (ADSCs) using an epifluorescence-based cell imaging system. In this study described a novel method for the detection of action potential-capable MNLCs differentiated from ADSCs using voltage-sensitive dyes (VSDs). We compared the results of extracellular applied VSDs in a more detailed labeling of cellular processes with calcium indicators. MNLCs were maintained in culture medium and then loaded with the VSDs RH795. For the RH795 loading, cultures were maintained in a artificial cerebrospinal fluid (ACSF) buffer and incubated at 37°C in the dark. The cells were then washed 3 times and incubated for 60 minutes in ACSF buffer in the dark. With RH-795, a fluorescence change was observed in the frame immediately following the stimulation onset, reaching a maximum at 10–20 ms after stimulation onset and then decaying during the subsequent frames. This method allows for a repeatable fast and accurate stimulation of neurons derived from stem cell cultures to assess their differentiation state, which is capable of monitoring large amounts of cells.

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Introduction: MicroRNAs (miRNAs) are small and non-coding ribonucleic acids that play critical roles in regulation of host genome expression at post-transcriptional level. An individual miRNA is able to down-regulate multiple targeted mRNA transcripts. Therefore, minor changes in a miRNA expression may lead to significant alterations in the expression of different genes. During last two decades, miRNAs have emerged as key regulators of immune cell lineage differentiation, maturation, maintenance of immune homeostasis, and normal function. Multiples sclerosis (MS) is a chronic inflammatory disease that is characterized by infiltration of lymphocytes into the central nervous system (CNS), demyelination and axonal degeneration. Although causes of MS are still unknown, it is widely accepted that novel drug targets need to focus on both decreasing inflammation and promoting CNS repair. Recent researches about MS disease have shown that miRNAs are dysregulated in the immune system and CNS, which shows their role in the MS pathogenesis. Conclusion: Identification of specific expression patterns of miRNA in autoimmune diseases and a further comprehensive understanding of their role in the pathogenesis of different diseases offers promise of not only novel molecular diagnostic markers but also new gene therapy strategies for treating inflammatory autoimmune diseases. In this study, we review the latest findings about miRNA biogenesis and signatures in the CNS and immune cells of MS patients.

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Introduction: Long non-coding RNAs (lncRNAs) are regulatory molecules that set many vital processes in the cell. These regulatory RNAs, as an important component of the regulatory networks of genes and the expression of key genes involved in setting development, play an important role in neurological diseases of the central nervous system (CNS). The purpose of this study was to evaluate the regulatory functions of lncRNAs in the evolution of the CNS and an overview of their roles in the biology of neuropsychiatric diseases. More than half of all lncRNAs expressed in CNS cells and their regulated expression in the evolution and function of the nervous system are important. lncRNAs are involved in the development of different parts of the brain, specificity and differentiation of oligodendrocytes category, and terminal myelination. In addition, they have a role in regulation of vital functions, such as maintaining neural stem cells, neurogenesis and glyogenesis, homeostasis, and synaptic connections. lncRNAs are associated with the biological processes in the brain, such as the development of the hippocampus and aging. Conclusion: This review has shown that how lncRNA regulate vital processes in neurons in order to have a better understanding on the mechanisms of neurological diseases by RNA interference. Understanding the role of the regulatory RNAs interference and its impact on the biology of CNS can helpful in the field of prognosis, prediction of response to treatment, and pathological staging. Furthermore, it can be inhibited or controlled as novel therapeutic targets.

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Introduction: Rabies is a fatal neurological disease caused by rabies virus, the prototype of the Lyssavirus genus. Rabies virus (RABV) has tropism to the central nervous system (CNS) and its ability for replication leads to rabies disease. RABV replication in the CNS of majority of mammalian species, including humans, leads to fatal encephalomyelitis. The combination of virulence and pathogenicity factors enables RABV transmission from peripheral bite site to the neurons through the neuro-muscular route and leads to infection of the spinal cord and the brain. Prophylactic or therapeutic vaccine-induced antibodies are able to prevent the virus from entering the CNS. In the absence of neutralizing antibodies induced by the vaccine, the immune system is unable to control the virus after entering the nerve cells. RABV has the innate ability to evade the host immune defense responses and is able to enhance the efficiency of its entry into nerve cells, control host immune responses, and inhibit the antiviral immune stimulation. RABV delays apoptosis by controlling the expression of its proteins and adjusts the survival of infected cells according to its metabolic requirements. These mechanisms enable RABV to escape the host immune system and to proliferate in the neuronal cells. Conclusion: This study review show the different immune mechanisms involved in clearing the CNS from RABV infection and strategies that the virus uses against the host immune system in the CNS. In addition, mechanisms that the virus uses to replicate as well as the interaction of the virus with the host immune system are discussed.

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Introduction: Discovering the enzymes involved in steroid biosynthesis in the central nervous system and the ability of neurons and glial cells to produce steroids is one of the major findings of neurobiology over the last two decades. Unlike classical steroids, these neurosteroids influence neuronal function through direct interactions with neurotransmitter receptors at the cell surface. Conclusion: Extensive studies have shown diverse physiological and pharmacological effects for these compounds. Moreover, neurosteroids have been shown to be involved in different pathological procedures, including neurodegenerative and neuro inflammatory disorders as well as neuropsychiatric diseases. Herein, we will review different aspects of neurosteroid biosynthesis and functions as well as their involvement in the pathogenesis of brain diseases.

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Introduction: Several investigations revealed that the activation of the innate immune system plays a crucial role in the pathogenesis of numerous diseases. The innate immune system activation occurs in response to pathogens or tissue injury via pattern-recognition receptors that recognize pathogen-associated molecular patterns. The innate immune system triggered by these interactions besides the general responses causes a specific response to pathogen. In addition, this pathogen-specific innate response affects the specificity of the adaptive immune response through directing the differentiation of T-cells into functionally distinct subtypes. Although the mechanism(s) by which different Rabies viruses induce differential immune responses are unknown, recent studies indicate that the consequence of rabies virus infection is dependent upon the rapid stimulation of innate and adaptive immunity. The responses prevent viral entry into the central nervous system (CNS), where it can escape immunity. Laboratory strains that reach the CNS can be cleared and this has obviously happened in individuals with rabies. Thus, during rabies virus infection, pattern-recognition receptors of rabies can be recognized in the periphery and the CNS. Conclusion: To study these possibilities, the consequence of rabies infection in mice lacking adaptor myeloid differentiation factor 88 (MyD88) was demonstrated. Toll-like receptors (TLRs) signals, except for TLR3, activate proinflammatory reaction via the adaptor protein MYD88. Only mice lacking TLR7 displayed a marked mortality compared with MyD88 negative and control mice with deficits in both the development of peripheral immunity and rabies virus clearance from the CNS. The review demonstrated that TLR7 plays a vital role in controlling and directing of immune response against the rabies virus.

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Introduction: The regeneration capacity of the central nervous system (CNS) is very limited in the traumatic and non-traumatic injuries. Spinal cord injury (SCI) is the most common traumatic injuries in the CNS. Cell therapies have been tested to repair the neurodegenerative conditions of the CNS by different type of stem cells. Cell Therapy approaches focused on targeting the pathophysiology of SCI, in particular to replace lost neuronal and/or glial cells, provide a more favorable growth environment and neutralize inhibitory molecules. Neural stem/progenitor cells, glial precursors, olfactory ensheathing glial cells, mesenchymal stem cells, and Schwann cells are commonly used as the traditional cell transplants in experimental SCI studies, which may induce some advantages and/or disadvantages. It has been indicated that cellular transplantation had positive effects on animal models of some neuronal diseases. However, potential limitations and some concerns regarding the immunity of cell therapy are considered. Conclusion: The various stem cells candidates for cell therapy may provide positive therapeutic effects in SCI. These cells have some advantages and disadvantages. Among these cells, well-differentiated induced pluripotent stem cells and their derivatives in vitro can be used as an autologous source in SCI patients.

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Introduction: Due to lack of replacement of lost cells and neural factors in the affected area, regeneration and repair in the nervous system is complicated and has been of interest to researchers in recent years. Extensive studies in this field, such as cell therapy and tissue engineering methods, have provided novel approaches for nerve regeneration. The use of neural stem cells and scaffolds with sub-micron and nano-sized fiber structure similar to the natural extracellular matrix are the perfect choice for nervous tissue engineering. To this end two-dimensional (2D) and three-dimensional (3D) cultures have been used. 2D cell culture has been performed in hundreds of laboratories during the last two decades. This method of culture is elementary and does not reproduce the anatomy or physiology of a tissue for useful study. Therefore, a new method is needed to mimics the cell function and tissue architecture. Although design of 3D cell culture systems is more relevant, there are still several hurdles that must be overcome. When to be mentioned the 3D, investigators require for consider the design of matrix for supporting and proliferation of the cells. In general, scaffolds have been categorized in three groups, including natural, synthetic, and hybrid (natural & synthetic). Scaffolds combined with any chemical or physical properties are suitable for tissue engineering of the central nervous system if they are non-toxic, with size fiber of 200-600 nm, with the gradual degradation of the scaffold after implantation in the body, and with capability of cell growth and proliferation. Conclusion: Recent investigations demonstrated that 3D culture is more mature and relevant to human and animal physiology than 2D cell culture. The hybrid scaffolds are best choice for fiber diameter size and high capacity of cell proliferation. The purpose of this review is to provide a general overview of scaffold design by natural and synthetic polymers and their effects on regeneration of the central nervous system

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Introduction: Glial-derived growth factor (GDNF) is an important secretory protein that plays a crutial role in the growth and development of the central and peripheral nervous systems, especially the survival of dopaminergic adult neurons. Several investigations have shown the unique negative modulatoty role of GDNF in drug abuse. Conclusion: This study is a brief description on GDNF and its positive effects as a potential target for the treatment of drug addiction.

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Neurotrauma is one of the main medical problems that affect considerable number of population especially young persons in all countries. Neurotrauma not only is a serious threat for life but also creates various disabilities and consequently imposes large costs to society. Following central nervous system (CNS) injury, tissue damage occurs via primary and secondary mechanisms. Despite many attempts, there is no definite solution for repairing of damaged tissue of CNS. In recent years, stem cell therapy has opened a new way in front of scientists to address this problem. Today, several sources are available for neural repairing including embryonic, fetal, umbilical and adult stem cells. Embryonic stem cells have great proliferative capacity but their use is associated with ethical and immunological concerns. On the other hand, adult stem cells create an outstanding opportunity for autologous transplantation. In this regard, adult neural stem cells can produce real neural cell lines including neuron, astrocyte and oligodendrocyte. Although there are several questions about neural stem cell utilization such as the fate of stem cells and the control of cell dividing after transplantation, which need more basic studies, some clinical trials have been started in phase ׀ or ׀׀ especially for spinal cord injury.  In conclusion, we are in the beginning of the stem cell therapy for CNS repair, consequently scientists must move forward with caution.

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Enhanced immune cell trafficking into the central nervous system (CNS) and disruption of the blood brain barrier are pathophysiological hallmarks of neuroinflammatory disorders like multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). However, recent studies suggest that the coagulation and the contact-kinin system might also be involved in MS development. For instance, it was shown that the coagulation factor XII modulates immune cell function and bradykinin influences the integrity of the blood-brain barrier (BBB). High molecular weight kininogen (HMWK) is a central constituent of the contact-kinin system. Here, we identify HMWK as a critical player in neuroinflammation. Deficiency of HMWK renders mice less susceptible to EAE and was accompanied by decreased numbers of infiltrated lymphocytes into the CNS, whereas the distribution of immune cells was unaltered as determined by flow cytometry analysis. Preliminary in vitro migration experiments showed that HMWK leads to an enhanced immune cell trafficking through an endothelial cell layer. Altogether, our study indicates that HMWK inhibition reduces cell invasion during autoimmune CNS disease and may offer a novel strategy to combat MS

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Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) characterized by inflammatory and neurodegenerative processes. One of its pathophysiological hallmarks is demyelination, a consequence of oligodendroglial cell death leading supply shortfall and missing electrical insulation to axons. Demyelination induced consequences on neuronal network activity and subsequent behavior are still not fully understood. In order to characterize neuronal functionality following demyelination, we applied the cuprizone model. A diet including cuprizone leads to full CNS demyelination in five weeks and re-introduction of normal food promotes spontaneous remyelination. Therefore, we assessed a time course of the functional consequences of myelin gain and loss in mice in six experimental groups. They were tested for short and long term memory and locomotor abilities at different time points during and after cuprizone treatment. Performing the novel object recognition test by assessing the explorations of known or novel object, we evaluated short and long term memory abilities, which appeared impaired following the cuprizone administration in a time-dependent manner. Spontaneous remyelination promoted amelioration of the performance. Additionally, treated animals did not present obvious locomotor deficits but a sustained anxiety-like behavior which only partially improves upon remyelination. Demyelination of white matter fiber tracts and cortical areas associated to memory and cognition was evaluated with immunohistological staining using the proteolipid protein as a marker for adult oligodendrocytes. Indeed, cuprizone diet dramatically decreased the number of living cells while promoting astrocytosis axonal damage and activation of macrophages which physiologically remove the debris of damaged myelin. Taken together, our results show that CNS demyelination leads to impaired cognitive abilities in rodents; an effect that seems to be recover after remyelination.

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Noncoding ribonucleic acids micro-RNA is involved in the regulation of gene expression have major roles in the post-transcriptional level. A micro-RNA alone several causes down regulation of mRNA transcript of the target. Thus, small changes in the expression of a micro RNA may lead to significant changes in gene expression are different. Micro- RNA as key regulators of immune cell lineage differentiation, maturation, maintain homeostasis and function Known natural immunity. Multiple sclerosis is a chronic inflammatory disease which is characterized by lymphocytic infiltration central nervous system, loss of myelin and axonal damage is determined. Although the causes MS remains unknown, drug targets new to focus on reducing central nervous system inflammation and promote healing process is essential. Studies have shown that micro-RNA of Patients with Multiple Sclerosis in the immune system and the system Central nervous system are impaired, their role in the pathogenesis of MS show. The presence of micro-RNA expression patterns in autoimmune diseases such as multiple sclerosis and their role in the pathogenesis of various diseases, new therapeutic strategies for the treatment of autoimmune diseases, inflammatory gene suggests.

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Neuroinflammation as a protective mechanism for repairing tissue damage in the central nervous system (CNS), has been classified into two types: acute and chronic. It is characterized by the activation of microglia and astrocytes and the increase levels of different chemokines and cytokines. Neuroinflammation can be harmful, and it is a common pathological feature in neurodegenerative and psychiatric conditions. On the other word, neuroinflammation effects on important processes in the brain such as adult neurogenesis. Neurogenesis is the process by which new neurons are generated during the embryonic development of CNS and in the adult brain, and it has an important role in the repairing adult brain. Therefore, we review the effect of neuroinflammation on neurogenesis. Chronic neuroinflammation can impair to hippocampal neurogenesis in the adult brain. It has been proven that chronic neuroinflammation due to increased microglial activation and increased production of pro‐inflammatory cytokines (e.g. interleukin-1β, interleukin-6, and tumor necrosis factor-α.) has deleterious effects on neurogenesis. It has been also demonstrated that microglial activation by reducing cell proliferation and newborn cell survival leads to hippocampal neurogenesis dysfunction in the adult brain. It can be concluded that neurogenesis as a physiologic phenomenon in hippocampus affected by neuroinflammation. New studies in this field can be helped to treat related neurodegeneration disease. 

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Post-traumatic stress disorder (PTSD) is an anxiety disorder that can typically occur after traumatic events in which the individual felt sever helplessness or horror. PTSD has a lifetime prevalence of 5–8% and women show higher prevalence than in compared with men. Neuroinflammation is associated to anxiety and related disorders such as PTSD. It is an early, specialized immune reaction fallowing tissue damage and/or pathogen invasion in the central nervous system (CNS). Regarding the importance of anxiety disorders especially PTSD and their effect on patients' personal and social life, considering of the neuroinflammation in PTSD can be used for new treatment. Several studies have been reported that there is a relationship between neuroinflammation and PTSD. Current epidemiological evidence shows that increased expression of pro‐inflammatory cytokines such as interleukin-1β, interleukin-6, and tumor necrosis factor-α, and decreased anti-inflammatory factors have a key role in creating PTSD. Also, neuroinflammation induced by inhibition of the NADPH oxidase (NOX2) can lead to trigger the PTSD symptoms. Various inflammatory markers such as Cortisol, C-reactive protein (CRP), Th1 cytokines, and Th2 Cytokines are associated with PTSD. Furthermore, micro÷glial activation may also initiate inflammation and can be involved in PTSD. Thus, scrutinized research about PTSD and understanding of creating mechanisms of this disorder is essential and can provide grounds for its treatment.

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Depression is a mental disorder that results from changes in the central nervous system (CNS) that may result from immunological abnormalities. According to the World Health Organization, major depression will become the leading cause of disability worldwide. Accumulating evidence has indicated the existence of reciprocal communication pathways between nervous, endocrine and immune systems. The immune system affects the CNS through cytokines, which regulate brain activities and emotions. Cytokines affect the activity of the two biological systems that are most associated with the pathophysiology of depression: The hypothalamic-pituitary-adrenal axis and the catecholamine/sympathetic nervous system. Pro-inflammatory cytokines and stress are important in inflammatory and neurogenesis and neuroprotection. Stress induces pro-inflammatory cytokines over secretion, which result in activation the HPA axis and neurotransmitter turnover, thus leading to depression. The use of cytokine inhibitors and anti-inflammatory drug is effective in the treatment of the depression. Although there are known effective treatment for depression, fewer than half of these affected in the world. In this review calculated recent literature related to the effect of inflammation on the pathogenesis depression.

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Systemic Lupus Erythematosus (SLE) is a complex clinical syndrome which its components are less clearly recognized and includes heterogeneous demonstrations engaging both central and peripheral nervous system along with disabling effects. This disease is called "thousand faces" due to these heterogeneous demonstrations. This gap exists while 75% of adults and children with SLE may deal with its nervous demonstrations and experience disability during disease period. Different factors contribute to the body's immunity performance disorder including genetic, hormonal and environmental factors. However, disposing factors leading to nervous demonstrations in some patients are not clearly understood. Today, Lupus nervous involvement is considered as “the most clinical challenging ‘visceral’ involvement,” “causes high morbidity and mortality” and put a “heavy financial and economic and social burden on the society”. Lupus nervous involvement covers a wide range of clinical demonstration intensity. NPSLE was first described by Morris Kaposi in 1872. In 1999, ACR attempted to name and define neuro-psychotic syndromes recognized in SLE. Different CNS demonstrations of Lupus are investigated in this paper. Neurologic demonstrations of focal SLE, mostly the secondary ones, as vascular events is due to anti-phospholipid antibody. These demonstrations are usually acute and resist against treatment at first and can be accompanied by structural abnormalities in autopsy while pathogenesis mechanism of CNS demonstrations is less recognized and these demonstrations are harmful and develop slowly; they are reversible after treatment and usually not accompanied by structural pathology. Although headache and mood disorders are common neurologic complains of patients with SLE, seizure, brain vessel disease, acute confusional state, and neuropathy are the most common syndromes related to SLE. CNS demonstrations of SLE patients include: Cerebrovascular disease, Seizure, Myelopathy, Lupus psychosis, acute confusional state, Cognitive dysfunction, Movement disorder, Aseptic meningitis and demyelinating syndrome.