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Sample records for demyelinating disease masquerading

  1. Charcot-Marie-Tooth disease masquerading as acute demyelinating encephalomyelitis-like illness.

    PubMed

    Kim, Gun-Ha; Kim, Kyoung Min; Suh, Sang-Il; Ki, Chang-Seok; Eun, Baik-Lin

    2014-07-01

    X-linked Charcot-Marie-Tooth disease (CMTX1) is a clinically heterogeneous hereditary motor and sensory neuropathy with X-linked transmission. Common clinical manifestations of CMTX1 disease, as in other forms of Charcot-Marie-Tooth (CMT) disease, are distal muscle wasting and weakness, hyporeflexia, distal sensory disturbance, and foot deformities. Mutations in the connexin-32 gene (gap junction protein β1 [GJB1]) are responsible for CMTX1 disease. In this report, we describe a patient with CMTX1 disease presenting with recurrent attacks of transient and episodic acute demyelinating encephalomyelitis (ADEM)-like symptoms without previous signs of lower extremity weakness or foot deformities; the patient, as well as his asymptomatic mother, exhibited a novel GJB1 mutation (p.Met1Ile). Differential diagnosis of recurrent and transient ADEM-like illness, if unexplained, should include the possibility of CMTX1 disease.

  2. The innate immune system in demyelinating disease.

    PubMed

    Mayo, Lior; Quintana, Francisco J; Weiner, Howard L

    2012-07-01

    Demyelinating diseases such as multiple sclerosis are chronic inflammatory autoimmune diseases with a heterogeneous clinical presentation and course. Both the adaptive and the innate immune systems have been suggested to contribute to their pathogenesis and recovery. In this review, we discuss the role of the innate immune system in mediating demyelinating diseases. In particular, we provide an overview of the anti-inflammatory or pro-inflammatory functions of dendritic cells, mast cells, natural killer (NK) cells, NK-T cells, γδ T cells, microglial cells, and astrocytes. We emphasize the interaction of astroctyes with the immune system and how this interaction relates to the demyelinating pathologies. Given the pivotal role of the innate immune system, it is possible that targeting these cells may provide an effective therapeutic approach for demyelinating diseases.

  3. Th17 cells in autoimmune demyelinating disease

    PubMed Central

    2010-01-01

    Recently published studies in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) have demonstrated an association between the development of demyelinating plaques and the accumulation of Th17 cells in the central nervous system and periphery. However, a causal relationship has been difficult to establish. In fact, in reports published thus far, interleukin (IL)-17A deficiency or neutralization in vivo attenuates, but does not completely abrogate, EAE. There is growing evidence that clinically similar forms of autoimmune demyelinating disease can be driven by myelin-specific T cells of distinct lineages with different degrees of dependence on IL-17A production to achieve their pathological effects. While such observations cast doubts about the potential therapeutic efficacy of Th17 blocking agents in MS, the collective data suggest that IL-17A expression in peripheral blood mononuclear cells could serve as a surrogate biomarker of neuroinflammation and plaque formation and be a useful outcome measure for future clinical trials. PMID:20195867

  4. Demyelinating, degenerative, and vascular disease.

    PubMed

    Dooley, D M

    1977-01-01

    Fifty per cent of patients diagnosed as having multiple sclerosis, primary lateral sclerosis, or hereditary spinocerebellar disorders were observed to have enduring favorable changes in neurological function during the 15 to 27 months they have been followed. The patients who were the least severely disabled were benefitted the most by the stimulation and made the most rapid progress. For example, the patient having only an ataxic or a spastic gait typically was observed to improve faster than the patient having both an ataxic and a spastic gait. The long term effect of electrostimulation of the spinal cord on these patients is unknown. The purpose of the stimulation is to attempt to obtain an improvement in neurological function so that the patient may experience a better life style. It is not thought that the electrical current has any effect on the basic disease process. Electrostimulation over the posterior spinal roots and spinal cord, although not new, has not been used extensively for the treatment of patients with arterial disease. The patients who have responded the most dramatically to electrostimulation are those with vasospastic disorders. A larger percentage of patients showed a greater response to implanted stimulation than to transcutaneous stimulation. Electrostimulation of the nervous system is not designed to replace standard therapeutic measures of treatment of patients with vascular disease, but to supplement them.

  5. Immunopathophysiology of pediatric CNS inflammatory demyelinating diseases.

    PubMed

    Bar-Or, Amit; Hintzen, Rogier Q; Dale, Russell C; Rostasy, Kevin; Brück, Wolfgang; Chitnis, Tanuja

    2016-08-30

    Elucidating pathophysiologic mechanisms underlying the spectrum of pediatric-onset CNS demyelinating diseases, particularly those that may distinguish multiple sclerosis (MS) from other entities, promises to both improve diagnostics and guide more-informed therapeutic decisions. Observations that pediatric- and adult-onset MS share the same genetic and environmental risk factors support the view that these conditions represent essentially the same illness manifesting at different ages. Nonetheless, special consideration must be given when CNS inflammation manifests in early life, at a time when multiple organs (including immune and nervous systems) are actively maturing. CSF analysis in pediatric-onset MS points to chronic CNS inflammation, supported by observations from limited pathologic material available for study. Emerging results implicate abnormalities in both effector and regulatory T cell subsets, and potentially immune senescence, in children with MS. Although CNS-directed antibodies (including antibodies recognizing myelin antigens; Kir4.1) can be documented in pediatric-onset MS, their pathophysiologic significance (as in adults) remains unclear. This is in contrast to the presence of serum and/or CSF antibodies recognizing aquaporin-4, which, when measured using validated cell-based assays, supports the diagnosis of a neuromyelitis optica spectrum disorder, distinct from MS. Presence of anti-myelin oligodendrocyte glycoprotein antibodies documented with similar cell-based assays may also be associated with pathophysiologically distinct disease phenotypes in children. The substantial impact of pediatric-onset MS on normal brain development and function underscores the importance of elucidating both the immunobiology and neurobiology of disease. Ongoing efforts are aimed at developing and validating biological measures that define pathophysiologically distinct monophasic and chronic forms of pediatric CNS demyelination.

  6. Diagnostic pitfalls in spine surgery: masqueraders of surgical spine disease.

    PubMed

    Walcott, Brian P; Coumans, Jean-Valery C E; Kahle, Kristopher T

    2011-10-01

    Disorders of the spine are common in clinical medicine, and spine surgery is being performed with increasing frequency in the US. Although many patients with an established diagnosis of a true surgically treatable lesion are referred to a neurosurgeon, the evaluation of patients with spinal disorders can be complex and fraught with diagnostic pitfalls. While "common conditions are common," astute clinical acumen and vigilance are necessary to identify lesions that masquerade as surgically treatable spine disease that can lead to erroneous diagnosis and treatment. In this review, the authors discuss musculoskeletal, peripheral nerve, metabolic, infectious, inflammatory, and vascular conditions that mimic the syndromes produced by surgical lesions. It is possible that nonsurgical and surgical conditions coexist at times, complicating treatment plans and natural histories. Awareness of these diagnoses can help reduce diagnostic error, thereby avoiding the morbidity and expense associated with an unnecessary operation.

  7. Acute Demyelinating Disease after Oral Therapy with Herbal Extracts

    PubMed Central

    Kostianovsky, Alex; Maskin, Patricio; Noriega, María M.; Soler, Cristina; Bonelli, Ignacio; Riley, Claire S.; O'Connor, Kevin C.; Saubidet, Cristi´n López; Alvarez, Paulino A.

    2011-01-01

    Central nervous system demyelinating processes such as multiple sclerosis and acute disseminated encephalomyelitis constitute a group of diseases not completely understood in their physiopathology. Environmental and toxic insults are thought to play a role in priming autoimmunity. The aim of the present report is to describe a case of acute demyelinating disease with fatal outcome occurring 15 days after oral exposure to herbal extracts. PMID:21738505

  8. Involvement of morbilliviruses in the pathogenesis of demyelinating disease.

    PubMed

    Sips, G J; Chesik, D; Glazenburg, L; Wilschut, J; De Keyser, J; Wilczak, N

    2007-01-01

    Two members of the morbillivirus genus of the family Paramyxoviridae, canine distemper virus (CDV) and measles virus (MV), are well-known for their ability to cause a chronic demyelinating disease of the CNS in their natural hosts, dogs and humans, respectively. Both viruses have been studied for their potential involvement in the neuropathogenesis of the human demyelinating disease multiple sclerosis (MS). Recently, three new members of the morbillivirus genus, phocine distemper virus (PDV), porpoise morbillivirus (PMV) and dolphin morbillivirus (DMV), have been discovered. These viruses have also been shown to induce multifocal demyelinating disease in infected animals. This review focuses on morbillivirus-induced neuropathologies with emphasis on aetiopathogenesis of CNS demyelination. The possible involvement of a morbillivirus in the pathogenesis of multiple sclerosis is discussed.

  9. The spectrum of MOG autoantibody-associated demyelinating diseases.

    PubMed

    Reindl, Markus; Di Pauli, Franziska; Rostásy, Kevin; Berger, Thomas

    2013-08-01

    Myelin oligodendrocyte glycoprotein (MOG) has been identified as a target of demyelinating autoantibodies in animal models of inflammatory demyelinating diseases of the CNS, such as multiple sclerosis (MS). Numerous studies have aimed to establish a role for MOG antibodies in patients with MS, although the results have been controversial. Cell-based immunoassays using MOG expressed in mammalian cells have demonstrated the presence of high-titre MOG antibodies in paediatric patients with acute disseminated encephalomyelitis, MS, aquaporin-4-seronegative neuromyelitis optica, or isolated optic neuritis or transverse myelitis, but only rarely in adults with these disorders. These studies indicate that MOG antibodies could be associated with a broad spectrum of acquired human CNS demyelinating diseases. This Review article discusses the current literature on MOG antibodies, their potential clinical relevance, and their role in the pathogenesis of MOG antibody-associated demyelinating disorders.

  10. Intravenous transplantation of mouse embryonic stem cells attenuates demyelination in an ICR outbred mouse model of demyelinating diseases

    PubMed Central

    Pringproa, Kidsadagon; Sathanawongs, Anucha; Khamphilai, Chananthida; Sukkarinprom, Sarocha; Oranratnachai, Apichart

    2016-01-01

    Induction of demyelination in the central nervous system (CNS) of experimental mice using cuprizone is widely used as an animal model for studying the pathogenesis and treatment of demyelination. However, different mouse strains used result in different pathological outcomes. Moreover, because current medicinal treatments are not always effective in multiple sclerosis patients, so the study of exogenous cell transplantation in an animal model is of great importance. The aims of the present study were to establish an alternative ICR outbred mouse model for studying demyelination and to evaluate the effects of intravenous cell transplantation in the present developed mouse model. Two sets of experiments were conducted. Firstly, ICR outbred and BALB/c inbred mice were fed with 0.2% cuprizone for 6 consecutive weeks; then demyelinating scores determined by luxol fast blue stain or immunolabeling with CNPase were evaluated. Secondly, attenuation of demyelination in ICR mice by intravenous injection of mES cells was studied. Scores for demyelination in the brains of ICR mice receiving cell injection (mES cells-injected group) and vehicle (sham-inoculated group) were assessed and compared. The results showed that cuprizone significantly induced demyelination in the cerebral cortex and corpus callosum of both ICR and BALB/c mice. Additionally, intravenous transplantation of mES cells potentially attenuated demyelination in ICR mice compared with sham-inoculated groups. The present study is among the earliest reports to describe the cuprizone-induced demyelination in ICR outbred mice. Although it remains unclear whether mES cells or trophic effects from mES cells are the cause of enhanced remyelination, the results of the present study may shed some light on exogenous cell therapy in central nervous system demyelinating diseases. PMID:27904491

  11. An Occult Malignancy Behind a Demyelinating Disease

    PubMed Central

    Lo Presti, Saberio; Kanagarajah, Prashanth; Pirela, Daniela; Morlote, Diana; Cusnir, Mike

    2016-01-01

    We report a case of a 38-year-old man presenting with bilateral lower extremity weakness and paresthesias that progressed during a 4-month period to severe polyneuropathy forcing the patient to be bed bound. Throughout his multiple hospitalizations, he was treated erroneously for chronic inflammatory demyelinating polyneuropathy, without significant improvement in his symptoms. In addition, he developed hepatosplenomegaly (organomegaly); endocrinopathies such as diabetes mellitus, central hypogonadism, and hypothyroidism; monoclonal spike evidenced in the serum electrophoresis; and hyperpigmentation of skin, altogether consistent with POEMS syndrome. During his last hospitalization he developed excruciating pain on his left hip, and imaging revealed the presence of a 9 × 6 cm osteolytic mass with sclerotic rim in the left acetabulum. Biopsy of the mass confirmed an isolated IgG lambda plasmacytoma. The patient received radiation to his left acetabular lesion followed by left hip replacement. Subsequently, the patient underwent autologous bone marrow transplant. Eighteen months after his initial presentation, he had satisfactory clinical response and is functional without significant limitations. POEMS syndrome is a rare paraneoplastic syndrome secondary to an underlying plasma cell disorder, which can oftentimes be overlooked and misdiagnosed. The median age of presentation is 51 years, and only 31% of the cases occur in fairly young patients under the age of 45 as evidenced in this case. As clinicians, we should be aware of the constellation of features associated with POEMS syndrome and be able to recognize them promptly. PMID:27790622

  12. Inflammatory Demyelinating Diseases of Childhood: Case Report and Literature Review

    PubMed Central

    EKİZOĞLU, Esme; TEKTÜRK TOPALOĞLU, Pınar; YAPICI, Zuhal; ERAKSOY, Mefkûre

    2014-01-01

    Multiple sclerosis (MS) and acute disseminated encephalomyelitis (ADEM) are demyelinating inflammatory diseases, considered to have a striking pathophysiological resemblance. However, due to the differences in both clinical course and clinical approaches, it is important to differentiate between the two conditions, to plan further investigations and therapy protocols. These diseases have similar but also distinct clinical, radiological and cerebrospinal fluid (CSF) findings. ADEM is typically a monophasic disease of children. MS occurs generally in adult age, but uncommonly may develop in childhood with variable features. Our case is a 14 year-old-girl, presented with a three-month history of left hemiparesis, followed by right hemiparesis, cerebellar signs, myelitis and cortical visual disturbances. Based on the clinical follow-up, MR and CSF findings, our patient was diagnosed with relapsing tumefactive multiple sclerosis. Steroid treatment was not significantly effective, however the patient has benefited from plasmapheresis clinically and radiologically. Our patient is still being followed under the disease modifying therapy without any relapse.

  13. Chromatic visual evoked potentials in young patients with demyelinating disease.

    PubMed

    Pompe, Manca Tekavčič; Brecelj, Jelka; Kranjc, Branka Stirn

    2014-04-01

    The purpose of this study was to evaluate color vision in young patients with demyelinating disease both clinically and electrophysiologically. Thirty young patients (8-28 years, mean age 19 years) with demyelinating disease with or without a history of optic neuritis (ON) were investigated. Color vision was evaluated clinically with the Ishihara test and the Farnsworth-Munsell 100 hue (FM 100 hue) test and electrophysiologically with chromatic visual evoked potentials (cVEPs). Color deficiency axis and error score (ES) obtained with the FM 100 hue test were analyzed. cVEPs to isoluminant red-green (R-G) and blue-yellow (B-Y) stimuli were recorded. The stimulus was a 7 deg circle composed of horizontal sinusoidal gratings with a spatial frequency of 2 cycles/deg and 90% chromatic contrast. Onset-offset mode of stimulation (ON:OFF=300∶700  ms) was used. Since the majority of the patients were adults (>18  years), the negative wave (N wave) of the cVEP respones is the prominent part and therefore was analyzed. Sixty eyes were studied-22 with at least one episode of ON (ON group) and 38 without any clinically evident episode of ON (nON group). The average ES in the ON group was 179.18±171.8, whereas in the nON group it was 87.60±65.34. The average N-wave latency in the ON group was 144±44  ms for the R-G stimulus and 146±56  ms for the B-Y stimulus, whereas in the nON group, it was 117±13  ms for the R-G stimulus and 121±22  ms for the B-Y one. The average N-wave amplitude in the ON group was 9.3±7.1  μV for the R-G stimulus and 5.1±3.9  μV for the B-Y one, whereas in the nON group, it was 10.8±8.3  μV for the R-G stimulus and 6.4±4.3  μV for the B-Y one. A significant difference between the ON and the nON group was found: in the ON group, ES was higher (p=0.01) and N-wave latency was longer (p=0.01) compared with those in the nON group. The study showed that color vision is expectedly more affected in the ON

  14. Role of autoantibodies in acquired inflammatory demyelinating diseases of the central nervous system in children.

    PubMed

    Rostasy, Kevin; Reindl, Markus

    2013-12-01

    The recent detection of aquaporin-4 (AQP4) and myelin oligodendrocyte glycoprotein (MOG) autoantibodies in acquired inflammatory demyelinating diseases, such as neuromyelitis optica, or acute disseminated encephalomyelitis, and multiple sclerosis, in children strongly indicates that B-cell-dependent mechanisms contribute to the pathogenesis. This review aims to give an overview of the role of autoantibodies in inflammatory demyelinating pediatric diseases, with a focus on antibodies to AQP4 and MOG.

  15. Multiple 'Brown Tumors' Masquerading as Metastatic Bone Disease.

    PubMed

    Vaishya, Raju; Agarwal, Amit Kumar; Singh, Harsh; Vijay, Vipul

    2015-12-23

    'Brown tumors' are known as 'osteitis fibrosa cystica' or 'Von Recklinghausen's disease' of the bone. A high index of suspicion is required by the treating doctor for diagnosing a 'brown tumor' in its early stage. Clinical suspicion, along with laboratory and radiological investigations, is required to diagnose this condition. We present a case of a 65-year-old woman who had multiple bony lesions and a thyroid nodule, which was initially considered as a metastatic bone disease, but later turned out to be 'brown tumors.' In all cases with multiple osteolytic lesions, a possibility of 'brown tumor' must be kept in mind.

  16. Pulmonary Strongyloidiasis Masquerading as Exacerbation of Chronic Obstructive Pulmonary Disease

    PubMed Central

    Pradhan, Gourahari; Behera, Priyadarshini; Bhuniya, Sourin; Mohapatra, Prasanta Raghab; Turuk, Jyotirmayee; Mohanty, Srujana

    2016-01-01

    Pulmonary strongyloidiasis is an uncommon presentation of Strongyloides infection, usually seen in immunocompromised hosts. The manifestations are similar to that of acute exacerbation of chronic obstructive pulmonary disease (COPD). Therefore, the diagnosis of pulmonary strongyloidiasis could be challenging in a COPD patient, unless a high index of suspicion is maintained. Here, we present a case of Strongyloides hyperinfection in a COPD patient mimicking acute exacerbation, who was on chronic steroid therapy. PMID:27790284

  17. Infectious and Inflammatory Diseases Masquerading as Head and Neck Malignancy.

    PubMed

    Greene; Sandin; Hiemenz; Toney

    1994-01-01

    Lesions of the head and neck and upper respiratory tract can be quite difficult to diagnose at times when presenting symptoms and signs appear out of character or biopsy of affected tissue reveals nonspecific results. A heightened awareness of important historical facts such as place of birth and residence, travel and occupation may provide important clues to narrow the differential diagnosis. Not all destructive ulcers and tumors of the head and neck are malignant. Inflammatory and infectious diseases that mimic cancer are presented.

  18. Paraneoplastic syndrome: a masquerade of autoimmune inner ear disease.

    PubMed

    Greene, Jacqueline J; Keefe, Michael W; Harris, Jeffrey P; Matsuoka, Akihiro J

    2015-01-01

    Rare and diagnostically challenging, paraneoplastic syndromes can appear months to years before detection of their underlying neoplasms and are associated with rapidly progressive neurologic deficits, including cochleovestibulopathy and death. Less than 20 cases of paraneoplastic cochleovestibulopathy have been reported in the online database PubMed. We present three recent cases: one patient with a history of B-cell follicular lymphoma who developed dermatomyositis and hearing loss before detection of lymphoma recurrence in his anterior chest wall, a second patient with sudden asymmetric hearing loss, found to have a 12-cm renal mass before death, and a third with fluctuating bilateral hearing loss who was ultimately found to have a thymoma. Although characterized as type VI (non-immune rapidly progressive sensorineural hearing loss) within the Harris autoimmune inner ear disease classification system, the mechanism of paraneoplastic cochleovestibulopathy is not well understood. Although specific anti-neuronal antibodies such as anti-Hu may be associated with other paraneoplastic neurologic disorders, these antibodies have limited diagnostic utility with paraneoplastic cochleovestibulopathy. Steroids have limited efficacy with regard to hearing recovery, whereas intravenous immunoglobulin has been shown to be of benefit. These recent cases demonstrate how auditory and vestibular deficits may be indicative of a rare but potentially life-threatening occult neoplasm where timely diagnosis is critical. We believe that understanding paraneoplastic cochleovestibulopathy is of interest across a broad range of clinical practices.

  19. Central and peripheral demyelination

    PubMed Central

    Mehndiratta, Man Mohan; Gulati, Natasha Singh

    2014-01-01

    Several conditions cause damage to the inherently normal myelin of central nervous system, perepheral nervous system or both central and perepheral nervous system and hence termed as central demyelinating diseases, perepheral demyelinating diseases and combined central and perepheral demyelinating diseases respectively. Here we analysed and foccused on the etiology, prevalance, incidence and age of these demyelinating disorders. Clinical attention and various diagnostic tests are needed to adequately assess all these possibilities. PMID:24741263

  20. Therapeutic Approach to the Management of Pediatric Demyelinating Disease: Multiple Sclerosis and Acute Disseminated Encephalomyelitis.

    PubMed

    Brenton, J Nicholas; Banwell, Brenda L

    2016-01-01

    Acquired pediatric demyelinating diseases manifest acutely with optic neuritis, transverse myelitis, acute disseminated encephalomyelitis, or with various other acute deficits in focal or polyfocal areas of the central nervous system. Patients may experience a monophasic illness (as in the case of acute disseminated encephalomyelitis) or one that may manifest as a chronic, relapsing disease [e.g., multiple sclerosis (MS)]. The diagnosis of pediatric MS and other demyelinating disorders of childhood has been facilitated by consensus statements regarding diagnostic definitions. Treatment of pediatric MS has been modeled after data obtained from clinical trials in adult-onset MS. There are now an increasing number of new therapeutic agents for MS, and many will be formally studied for use in pediatric patients. There are important efficacy and safety concerns regarding the use of these therapies in children and young adults. This review will discuss acute management as well as chronic immunotherapies in acquired pediatric demyelination.

  1. Characterization of Oligodendroglial Populations in Mouse Demyelinating Disease Using Flow Cytometry: Clues for MS Pathogenesis

    PubMed Central

    Goings, Gwendolyn E.; Miller, Stephen D.

    2014-01-01

    Characterizing and enumerating cells of the oligodendrocyte lineage (OLCs) is crucial for understanding demyelination and therapeutic benefit in models of demyelinating disease in the central nervous system. Here we describe a novel method for the rapid, unbiased analysis of mouse OLCs using flow cytometry. The assay was optimized to maximize viable yield of OLCs and maintain OLC antigen integrity. Panels of antibodies were assembled for simultaneous analysis of seven antigens on individual cells allowing for characterization of oligodendroglial cells throughout the lineage. We verified the utility of the assay with cultured OLCs and through a time course of developmental myelination. Next we employed the assay to characterize OLC populations in two well-characterized models of demyelination: cuprizone-induced demyelination and experimental autoimmune encephalomyelitis (EAE). In EAE we observed a dramatic loss of mature oligodendrocytes coincident with a dramatic expansion of oligodendrocyte progenitors cells (OPCs) at the onset of disease suggesting an attempt of the host to repair myelin. This expanded OPC pool was maintained through remission and relapse suggesting an arrest in differentiation in the face of the chronic autoimmune T cell-mediated inflammatory response. These robust, reproducible changes in OLCs through disease provide a rapid quantitative global analysis of myelin-producing cells in the adult mouse brain and important information regarding effects of disease on oligodendroglial proliferation/differentiation which is useful for defining the pathogenesis and therapy of MS. PMID:25247590

  2. Rat sleep and eye movement density as biological markers of demyelinating disease.

    PubMed

    Anch, A M; Laposky, A D

    Myelin mutants provide an opportunity to study neurophysiological and behavioral effects of demyelination. The taiep rats are myelin mutants with progressive demyelination of the central nervous system (CNS), resulting in five neurological symptoms: tremor, ataxia, immobility, epilepsy, and paralysis. The demyelination affects the brainstem, an important area in the control of sleep. This study compared eye movement density (EMD) in taiep vs. normal control rats during paradoxical sleep (PS). It was hypothesized that taiep rats would have significantly reduced EMD during PS in comparison to normal controls due to their demyelinating disease. In addition, demyelination of brainstem structures would suggest possible changes in sleep-wake structure. Hence, we compared sleep-wake stages in taiep vs. normal, control rats. The results confirmed significantly reduced EMD during PS in taiep rats compared to normal rats during the 12-h (light) recording period. In addition, analysis of EMD values across the 12-h light period revealed significant differences in EMD values as a function of time of day in the taeip rats only. Comparison of waking and sleep values across the 12-h light phase revealed an "immobility episode" in three taiep rats, which was not present in normal controls. In addition, PS percentage was significantly lower and low-voltage sleep was significantly higher in taiep rats. These results suggest that EMD, immobility episodes, and sleep architecture may be useful as measurable biological events in the study of demyelinating disease. The results were discussed in terms of possible mechanisms underlying these differences, as well as possible implications for future studies.

  3. Association of Demyelinating and Inflammatory Bowel Diseases: A Case Series and Overview of the Literature

    PubMed Central

    ATMACA, Murat Mert; ALTIOKKA UZUN, Güneş; SHUGAIV, Erkingül; KÜRTÜNCÜ, Murat; ERAKSOY, Mefküre

    2015-01-01

    Neurological complications of inflammatory bowel diseases (i.e., ulcerative colitis and Crohn’s disease) can be summarized as a combination of neuromuscular manifestations, cerebrovascular and demyelinating diseases that can be seen in approximately 3% of patients. In addition, asymptomatic cerebral white matter lesions may be detected in these patients. Clustering of diseases within families may be explained by the exposure to similar environmental factors, shared genes, or complex interactions between genetic and environmental factors. Here we report an epileptic patient with Crohn’s disease and cerebral white matter lesions, a family with ulcerative colitis and multiple sclerosis and two patients who have both multiple sclerosis and Crohn’s disease.

  4. Molecular analysis of the genes causing recessive demyelinating Charcot-Marie-Tooth disease in Japan.

    PubMed

    Hayashi, Makiko; Abe, Akiko; Murakami, Tatsufumi; Yamao, Satoshi; Arai, Hidee; Hattori, Hideji; Iai, Mizue; Watanabe, Kyoko; Oka, Nobuyuki; Chida, Keiji; Kishikawa, Yumiko; Hayasaka, Kiyoshi

    2013-05-01

    Charcot-Marie-Tooth disease (CMT), the most common hereditary neuropathy, has been classified into two types, demyelinating and axonal types. We previously analyzed the genes causing dominant demyelinating CMT in 227 Japanese patients to identify the genetic background, but could not find any mutations in 110 patients. To investigate the frequency of patients with autosomal recessive demyelinating CMT (CMT4) mutations, we analyzed the coding sequence of known causative genes of CMT4 in 103 demyelinating CMT patients, excluding seven patients owing to lack of specimens. We found one patient with a GDAP1 mutation, one patient with an MTMR2 mutation, two patients with SH3TC2/KIAA1985 mutations and three patients with FGD4 mutations. Twelve patients, including five previously detected patients with PRX mutations, were diagnosed as CMT4, accounting for 5.5% of demyelinating CMT. In the patient with GDAP1 mutation, only one mutation inherited from his mother was detected by genomic sequencing. Analysis by reverse transcription polymerase chain reaction using messenger RNA (mRNA) from the patient's leukocytes revealed the absence of transcription from the allele inherited from his father, suggesting the existence of one more mutation leading to a lack or destabilization of mRNA. Most patients carrying CMT4 gene mutations present with early-onset and slowly progressive symptoms, which may be associated with the function of mutants. We could not identify the disease-causing gene in 96 patients (about 45%). Further studies including studies with next-generation sequencers will be required to identify the causative gene in Japanese CMT.

  5. PERK activation preserves the viability and function of remyelinating oligodendrocytes in immune-mediated demyelinating diseases.

    PubMed

    Lin, Yifeng; Huang, Guangcun; Jamison, Stephanie; Li, Jin; Harding, Heather P; Ron, David; Lin, Wensheng

    2014-02-01

    Remyelination occurs in multiple sclerosis (MS) lesions but is generally considered to be insufficient. One of the major challenges in MS research is to understand the causes of remyelination failure and to identify therapeutic targets that promote remyelination. Activation of pancreatic endoplasmic reticulum kinase (PERK) signaling in response to endoplasmic reticulum stress modulates cell viability and function under stressful conditions. There is evidence that PERK is activated in remyelinating oligodendrocytes in demyelinated lesions in both MS and its animal model, experimental autoimmune encephalomyelitis (EAE). In this study, we sought to determine the role of PERK signaling in remyelinating oligodendrocytes in MS and EAE using transgenic mice that allow temporally controlled activation of PERK signaling specifically in oligodendrocytes. We demonstrated that persistent PERK activation was not deleterious to myelinating oligodendrocytes in young, developing mice or to remyelinating oligodendrocytes in cuprizone-induced demyelinated lesions. We found that enhancing PERK activation, specifically in (re)myelinating oligodendrocytes, protected the cells and myelin against the detrimental effects of interferon-γ, a key proinflammatory cytokine in MS and EAE. More important, we showed that enhancing PERK activation in remyelinating oligodendrocytes at the recovery stage of EAE promoted cell survival and remyelination in EAE demyelinated lesions. Thus, our data provide direct evidence that PERK activation cell-autonomously enhances the survival and preserves function of remyelinating oligodendrocytes in immune-mediated demyelinating diseases.

  6. Absence of Multiple Sclerosis and Demyelinating Diseases among Lacandonians, a Pure Amerindian Ethnic Group in Mexico

    PubMed Central

    Flores, Jose; González, Silvia; Morales, Ximena; Yescas, Petra; Ochoa, Adriana; Corona, Teresa

    2012-01-01

    Multiple Sclerosis (MS) is a highly polymorphic disease characterized by different neurologic signs and symptoms. In MS, racial and genetic factors may play an important role in the geographic distribution of this disease. Studies have reported the presence of several protective alleles against the development of autoimmune disorders. In the case of MS, however, they help define MS as a complex disease, and confirm the importance of environmental agents as an independent variable not associated with ethnicity. We carried out an on-site epidemiological study to confirm the absence of MS or NMO among Lacandonians, a pure Amerindian ethnic group in Mexico. We administered a structured interview to 5,372 Lacandonians to assess by family background any clinical data consistent with the presence of a prior demyelinating event. Every participating subject underwent a comprehensive neurological examination by a group of three members of the research team with experience in the diagnosis and treatment of demyelinating disorders to detect clinical signs compatible with a demyelinating disease. We did not find any clinical signs compatible with multiple sclerosis among study participants. PMID:22973516

  7. Harnessing GPR17 Biology for Treating Demyelinating Disease

    DTIC Science & Technology

    2012-10-01

    multiple sclerosis . Our studies demonstrate that GPR17-deficient mice developed less severe disease and recovered faster from paralysis. Moreover, these mice showed reduced CNS-targeted pathogenic immune responses. These results provide us a strong basis to pursue drugbased treatment for this disease in the

  8. Directional diffusivity as a magnetic resonance (MR) biomarker in demyelinating disease

    NASA Astrophysics Data System (ADS)

    Benzinger, Tammie L. S.; Cross, Anne H.; Xu, Junqian; Naismith, Robert; Sun, Shu-Wei; Song, Sheng-Kwei

    2007-09-01

    Directional diffusivities derived from diffusion tensor magnetic resonance imaging (DTI) measurements describe water movement parallel to (λ ||, axial diffusivity) and perpendicular to (λ⊥radial diffusivity) axonal tracts. λ || and λ⊥ have been shown to differentially detect axon and myelin abnormalities in several mouse models of central nervous system white matter pathology in our laboratory. These models include experimental autoimmune encephalomyelitis (EAE), (1) myelin basic protein mutant mice with dysmyelination and intact axons, (2) cuprizone-induced demyelination, and remyelination, with reversible axon injury (2, 3) and a model of retinal ischemia in which retinal ganglion cell death is followed by Wallerian degeneration of optic nerve, with axonal injury preceding demyelination. (4) Decreased λ|| correlates with acute axonal injury and increased λ⊥ indicates myelin damage. (4) More recently, we have translated this approach to human MR, investigating acute and chronic optic neuritis in adults with multiple sclerosis, brain lesions in adults with multiple sclerosis, and acute disseminated encephalomyelitis (ADEM) in children. We are also investigating the use of this technique to probe the underlying structural change of the cervical spinal cord in acute and chronic T2- hyperintense lesions in spinal stenosis, trauma, and transverse myelitis. In each of these demyelinating diseases, the discrimination between axonal and myelin injury which we can achieve has important prognostic and therapeutic implications. For those patients with myelin injury but intact axons, early, directed drug therapy has the potential to prevent progression to axonal loss and permanent disability.

  9. [A case of asymmetric demyelinating neuropathy in a patient with chronic graft-versus-host disease].

    PubMed

    Matsumoto, Hideyuki; Seki, Naoko; Yamamoto, Tomotaka; Oshima, Kumi; Asai, Takashi; Motokura, Toru; Ugawa, Yoshikazu; Goto, Jun; Tsuji, Shoji

    2005-10-01

    A 47-year-old man, who suffered from acute lymphocytic leukemia at 45 years old and was treated with hematopoietic stem cell transplantation at 46 years old after the induction of complete remission by the standard chemotherapy, developed the symptoms of chronic graft-versus-host disease (cGVHD) such as dry eyes, dry mouth, skin thickening, skin scaling, skin pigmentation and impaired liver function. He was admitted to our hospital because of the acute development of diplopia and weakness of his left upper extremity accompanying with the exacerbation of other symptoms of cGVHD. Neurological examinations revealed the right abducens nerve palsy and asymmetric muscular weakness of the extremities; the proximal part of the left upper extremity and the distal part of the right upper extremity were markedly involved. Neurophysiological studies including magnetic motor root stimulation revealed demyelinating neuropathy specifically involving the motor nerves. On the basis of these findings, a diagnosis of peripheral neuropathy associated with cGVHD was made. Nighteen reports are available on peripheral neuropathy in cGVHD patients, but to date little is known about the pathophysiology of this condition. Most of those patients have been diagnosed as having symmetric demyelinating polyneuropathy, such as Guillain-Barré syndrome or chronic inflammatory demyelinating polyneuropathy. In this study, contrary to previous reports, the asymmetric involvement of motor nerves is noteworthy. Accumulation and further analyses of the cases like the present case are necessary to elucidate the pathogenesis of peripheral neuropathy in cGVHD.

  10. β2-Integrins in demyelinating disease: not adhering to the paradigm

    PubMed Central

    Hu, Xianzhen; Wohler, Jillian E.; Dugger, Kari J.; Barnum, Scott R.

    2010-01-01

    The β2-integrins are a subfamily of integrins expressed on leukocytes that play an essential role in leukocyte trafficking, activation, and many other functions. Studies in EAE, the animal model for multiple sclerosis, show differential requirements for β2-integrins in this disease model, ranging from critical in the case of LFA-1 (CD11a/CD18) to unimportant in the case of CD11d/CD18. Importantly, expression of β2-integrins on T cell subsets provides some clues as to the function(s) these adhesion molecules play in disease development. For example, transferred EAE studies have shown that Mac-1 (CD11b/CD18) expression on αβ T cells is critical for disease development, and the absence of LFA-1 on Tregs in recipient mice results in exacerbated disease. In this review, we summarize recent findings regarding the role of β2-integrins in demyelinating disease and new information about the role of β2-integrins with respect to alterations in Treg numbers and function. In addition, we discuss the potential for targeting β2-integrins in human demyelinating disease in light of the recent animal model studies. PMID:20007244

  11. beta2-integrins in demyelinating disease: not adhering to the paradigm.

    PubMed

    Hu, Xianzhen; Wohler, Jillian E; Dugger, Kari J; Barnum, Scott R

    2010-03-01

    The beta(2)-integrins are a subfamily of integrins expressed on leukocytes that play an essential role in leukocyte trafficking, activation, and many other functions. Studies in EAE, the animal model for multiple sclerosis, show differential requirements for beta(2)-integrins in this disease model, ranging from critical in the case of LFA-1 (CD11a/CD18) to unimportant in the case of CD11d/CD18. Importantly, expression of beta(2)-integrins on T cell subsets provides some clues as to the function(s) these adhesion molecules play in disease development. For example, transferred EAE studies have shown that Mac-1 (CD11b/CD18) expression on alphabeta T cells is critical for disease development, and the absence of LFA-1 on Tregs in recipient mice results in exacerbated disease. In this review, we summarize recent findings regarding the role of beta(2)-integrins in demyelinating disease and new information about the role of beta(2)-integrins with respect to alterations in Treg numbers and function. In addition, we discuss the potential for targeting beta(2)-integrins in human demyelinating disease in light of the recent animal model studies.

  12. Serum antibodies against central nervous system proteins in human demyelinating disease.

    PubMed Central

    Newcombe, J; Gahan, S; Cuzner, M L

    1985-01-01

    An immunoblotting technique has been used to screen serum samples from patients with demyelinating disease for antibody directed against central nervous system proteins. Antibodies of the IgM, IgG and IgA class directed against one or more of the particulate fraction proteins tubulin, myelin basic protein, 69 K neurofilament protein, glial fibrillary acidic protein, myelin associated glycoprotein or Wolfgram protein were present in 94, 54 and 47%, respectively, of multiple sclerosis sera examined. IgM antibodies against tubulin and myelin basic protein predominated. A similar antibody spectrum was seen in a significant proportion of sera from patients with optic neuritis, subacute sclerosing panencephalitis and motor neurone disease, in which primary or secondary demyelination occurs. Antibodies of all three classes directed against the 169 K and 220 K neurofilament proteins and against some unidentified proteins of human peripheral nerve, kidney, liver, spleen and skeletal muscle were detected in sera from healthy subjects and patients with neurological disease. Images Fig. 1 Fig. 2 PMID:2579754

  13. Physiological Dynamics in Demyelinating Diseases: Unraveling Complex Relationships through Computer Modeling

    PubMed Central

    Coggan, Jay S.; Bittner, Stefan; Stiefel, Klaus M.; Meuth, Sven G.; Prescott, Steven A.

    2015-01-01

    Despite intense research, few treatments are available for most neurological disorders. Demyelinating diseases are no exception. This is perhaps not surprising considering the multifactorial nature of these diseases, which involve complex interactions between immune system cells, glia and neurons. In the case of multiple sclerosis, for example, there is no unanimity among researchers about the cause or even which system or cell type could be ground zero. This situation precludes the development and strategic application of mechanism-based therapies. We will discuss how computational modeling applied to questions at different biological levels can help link together disparate observations and decipher complex mechanisms whose solutions are not amenable to simple reductionism. By making testable predictions and revealing critical gaps in existing knowledge, such models can help direct research and will provide a rigorous framework in which to integrate new data as they are collected. Nowadays, there is no shortage of data; the challenge is to make sense of it all. In that respect, computational modeling is an invaluable tool that could, ultimately, transform how we understand, diagnose, and treat demyelinating diseases. PMID:26370960

  14. Tangier's disease: An uncommon cause of facial weakness and non-length dependent demyelinating neuropathy

    PubMed Central

    Nagappa, Madhu; Taly, Arun B.; Mahadevan, Anita; Pooja, M.; Bindu, P. S.; Chickabasaviah, Y. T.; Gayathri, N.; Sinha, Sanjib

    2016-01-01

    Tangier disease is an autosomal recessive disorder characterized by an abnormal accumulation of cholesterol esters in various organs secondary to adenotriphosphate binding cassette transporter A-1 (ABCA-1) transporter deficiency and disrupted reverse cholesterol transport. It causes neuropathy in half of the affected individuals. We present the clinical, electrophysiological, and histopathological findings in a middle aged gentleman of Tangier disease who was initially misdiagnosed leprosy and treated with antileprosy drugs. The presence of a demyelinating neuropathy on electrophysiology in a patient with predominant upper limb involvement and facial diplegia should raise the suspicion of Tangier disease. The characteristic lipid profile of Tangier disease was noted in this patient viz. extremely low high density lipoprotein (HDL), elevated triglyceride (TG), and reduced apolipoprotein A1. Estimation of serum lipids should form a part of routine evaluation in order to avoid misdiagnosis. PMID:27011649

  15. Ultrasonographic nerve enlargement of the median and ulnar nerves and the cervical nerve roots in patients with demyelinating Charcot-Marie-Tooth disease: distinction from patients with chronic inflammatory demyelinating polyneuropathy.

    PubMed

    Sugimoto, Takamichi; Ochi, Kazuhide; Hosomi, Naohisa; Takahashi, Tetsuya; Ueno, Hiroki; Nakamura, Takeshi; Nagano, Yoshito; Maruyama, Hirofumi; Kohriyama, Tatsuo; Matsumoto, Masayasu

    2013-10-01

    Demyelinating Charcot-Marie-Tooth disease (CMT) and chronic inflammatory demyelinating polyneuropathy (CIDP) are both demyelinating polyneuropathies. The differences in nerve enlargement degree and pattern at multiple evaluation sites/levels are not well known. We investigated the differences in nerve enlargement degree and the distribution pattern of nerve enlargement in patients with demyelinating CMT and CIDP, and verified the appropriate combination of sites/levels to differentiate between these diseases. Ten patients (aged 23-84 years, three females) with demyelinating CMT and 16 patients (aged 30-85 years, five females) with CIDP were evaluated in this study. The nerve sizes were measured at 24 predetermined sites/levels from the median and ulnar nerves and the cervical nerve roots (CNR) using ultrasonography. The evaluation sites/levels were classified into three regions: distal, intermediate and cervical. The number of sites/levels that exhibited nerve enlargement (enlargement site number, ESN) in each region was determined from the 24 sites/levels and from the selected eight screening sites/levels, respectively. The cross-sectional areas of the peripheral nerves were markedly larger at all evaluation sites in patients with demyelinating CMT than in patients with CIDP (p < 0.01). However, the nerve sizes of CNR were not significantly different between patients with either disease. When we evaluated ESN of four selected sites for screening from the intermediate region, the sensitivity and specificity to distinguish between demyelinating CMT and CIDP were 0.90 and 0.94, respectively, with the cut-off value set at four. Nerve ultrasonography is useful to detect nerve enlargement and can clarify morphological differences in nerves between patients with demyelinating CMT and CIDP.

  16. Consensus Statement on medication use in multiple sclerosis by the Spanish Society of Neurology's study group for demyelinating diseases.

    PubMed

    García-Merino, A; Fernández, O; Montalbán, X; de Andrés, C; Oreja-Guevara, C; Rodríguez-Antigüedad, A; Arbizu, T

    2013-01-01

    Treatments for multiple sclerosis therapy are rapidly evolving. It is believed that new drugs will be approved in the near future, thereby changing current indications for treatment. In this context, the Spanish Society of Neurology's study group on demyelinating diseases, which evaluates medication use in MS, has decided to draw up a consensus statement on the current indications and guidelines for multiple sclerosis treatment.

  17. The TIM-3 pathway ameliorates Theiler's murine encephalomyelitis virus-induced demyelinating disease.

    PubMed

    Kaneyama, Tomoki; Tomiki, Hiroki; Tsugane, Sayaka; Inaba, Yuji; Ichikawa, Motoki; Akiba, Hisaya; Yagita, Hideo; Kim, Byung S; Koh, Chang-Sung

    2014-07-01

    Infection by Theiler's murine encephalomyelitis virus (TMEV) in the central nervous system (CNS) induces an immune-mediated demyelinating disease in susceptible mouse strains and serves as a relevant infection model for human multiple sclerosis. T-cell immunoglobulin and mucin domain-3 (TIM-3) has been demonstrated to play a crucial role in the maintenance of peripheral tolerance. In this study, we examined the regulatory role of the TIM-3 pathway in the development of TMEV-induced demyelinating disease (TMEV-IDD). The expression of TIM-3 was increased at both protein and mRNA levels in the spinal cords of mice with TMEV-IDD compared with naive controls. In addition, by utilizing a blocking mAb, we demonstrate that TIM-3 negatively regulates TMEV-specific ex vivo production of IFN-γ and IL-10 by CD4(+) T cells and IFN-γ by CD8(+) T cells from the CNS of mice with TMEV-IDD at 36 days post-infection (dpi). In vivo blockade of TIM-3 by using the anti-TIM-3 mAb resulted in significant exacerbation of the development of TMEV-IDD both clinically and histologically. The number of infiltrating mononuclear cells in the CNS was also increased in mice administered with anti-TIM-3 mAb both at the induction phase (10 dpi) and at the effector phase (36 dpi). Flow cytometric analysis of intracellular cytokines revealed that the number of CD4(+) T cells producing TNF, IL-4, IL-10 and IL-17 was significantly increased at the effector phase in the CNS of anti-TIM-3 mAb-treated mice. These results suggest that the TIM-3 pathway plays a critical role in the regulation of TMEV-IDD.

  18. Characterization of the spectrum of Korean inflammatory demyelinating diseases according to the diagnostic criteria and AQP4-Ab status

    PubMed Central

    2014-01-01

    Background The relative frequencies of demyelinating diseases among Korean patients with idiopathic inflammatory demyelinating disease of the central nervous system (IIDD) have not been sufficiently studied. We therefore describe a cohort of 203 patients with IIDD from three centers in Korea whose syndromes were identified precisely according to international clinical criteria and autoantibody to aquaporin 4 (AQP4-Ab) status. Methods In total, 260 consecutive patients were screened and 203 were included from three hospitals in Korea. All were tested for AQP4-Ab by using a cell-based assay. Patients who met the criteria for definite neuromyelitis optica (NMO) or had a positive AQP4-Ab test result were defined as the NMO group. Among the others, patients were assessed if they had acute disseminated encephalomyelitis, multiple sclerosis (MS), acute transverse myelitis, optic neuritis, or other demyelinating disease as a clinically isolated syndrome of the brain. Results Eighteen percent of patients were classified as the NMO group, 2% as acute disseminated encephalomyelitis, 18% as MS, 41% as acute transverse myelitis, 11% as optic neuritis, and 8% as other clinically isolated syndrome of the brain. AQP4-Ab was positive in 18% of patients and the relative frequency of NMO to MS (NMO/MS ratio) was 1.06. The mean duration of follow up in our patients was 64 months. Conclusions Among Korean patients with idiopathic inflammatory demyelinating diseases, the incidence of NMO may be similar to that of MS, and the overall positivity of AQP4-Ab could be lower than previously reported. In addition, acute transverse myelitis that is not associated with MS or NMO can be relatively common in these patients. Further population-based studies with AQP4-Ab are needed to determine the exact incidence of NMO and other idiopathic inflammatory demyelinating diseases in Korea. PMID:24779645

  19. γδT Cells: the Overlooked T cell Subset in Demyelinating Disease

    PubMed Central

    Wohler, Jillian E.; Smith, Sherry S.; Barnum, Scott R.

    2015-01-01

    γδ T cells represent a small subpopulation of T cells that express a restricted repertoire of T cell receptors and, unlike αβ T cells, function more as cells of the innate immune system. These cells are found in skin and mucosal sites as well as secondary lymphoid tissues and, frequently act as first line of defense sentinels. γδ T cells have been implicated in the pathogenesis of demyelinating disease although little was known regarding their trafficking and effector functions. In this brief review we highlight recent studies demonstrating that γδ T cells migrate rapidly to the CNS during experimental autoimmune encephalomyelitis (EAE), the animal model for multiple sclerosis. γδ T cell trafficking to the CNS is independent of β2-integrins and occurs well before onset of clinical signs of disease, peaking early during the acute phase of disease. γδ T cell-mediated production of inflammatory cytokines including IFN-γ and TNF-α appears critical for EAE development, suggesting these cells may set the stage for activation of other subsets of infiltrating effector cells. These data suggest that γδ T cells or subsets of γδ T cells may represent a new therapeutic target in demeylinating disease. PMID:19610090

  20. gammadelta T cells: the overlooked T-cell subset in demyelinating disease.

    PubMed

    Wohler, Jillian E; Smith, Sherry S; Barnum, Scott R

    2010-01-01

    gammadelta T cells represent a small subpopulation of T cells expressing a restricted repertoire of T-cell receptors and, unlike alphabeta T cells, function more as cells of the innate immune system. These cells are found in skin and mucosal sites as well as secondary lymphoid tissues and frequently act as first line of defense sentinels. gammadelta T cells have been implicated in the pathogenesis of demyelinating disease, although little was known regarding their trafficking and effector functions. In this Mini-Review, we highlight recent studies demonstrating that gammadelta T cells migrate rapidly to the CNS during experimental autoimmune encephalomyelitis (EAE), the animal model for multiple sclerosis. gammadelta T-cell trafficking to the CNS is independent of beta(2)-integrins and occurs well before onset of clinical signs of disease, peaking early during the acute phase of disease. gammadelta T-cell-mediated production of inflammatory cytokines, including interferon-gamma and tumor necrosis factor-alpha, appears critical for EAE development, suggesting that these cells may set the stage for activation of other subsets of infiltrating effector cells. These data suggest that gammadelta T cells or subsets of gammadelta T cells may represent a new therapeutic target in demeylinating disease.

  1. Low Prevalence of Sleep Disorders in Demyelinating Disease in a Northern Tenerife Population

    PubMed Central

    González-Platas, Montserrat; González-Platas, Javier; Bermúdez-Hernández, Moises; Pérez-Martín, Maria Yaiza; Croissier-Elías, Cristina; Pérez-Lorensu, Pedro Javier

    2016-01-01

    Study Objectives: Sleep disorders are seen in patients with demyelinating disease (DD) more often than in the general population. Combination of physical and psychological factors such as pain, spasms, nocturia, depression, anxiety, or medication effects could contribute to sleep disruption. Frequently, these disturbances have a major impact on health and quality of life of patients. The aim of this study was to estimate the prevalence of sleep disorders in patients seen in the DD consultation. Methods: 240 patients; mean age 43 years, 187 women; 163 patients with multiple sclerosis (MS): 144 relapsing-remitting, 19 progressive forms, 36 clinically isolated syndrome, 26 radiological isolated syndrome, and 15 patients with others DD. All participants completed questionnaires: Pittsburgh, Epworth, and Stanford scales, indirect symptoms of RLS and Obstructive Sleep Apnea, Fatigue Severity Scale, and Multiple Sclerosis Quality of Life-54. Results: Moderate/severe insomnia 12.5%, OSA 5.8%, RLS 9.6% (confirmed 3 cases), narcolepsy 0, fatigue (> 4) 24.6%. Physical QoL 66.6 ± 19.6, Mental QoL 66.1 ± 21.9. Patients with an established diagnosis showed higher scores on insomnia compared to the group of CIS and RIS (F = 3.85; p = 0.023), no differences were in the other parameters. Fatigue showed high correlation with insomnia (r = 0.443; p < 0.001), RLS (r = 0.513; p < 0.001), and sleepiness (r = 0.211; p = 0.001). None of the variables included in the regression model were shown to be predictors of Physical and Mental QoL. Conclusions: A high percentage of our sample sleeps well. Emphasize the low prevalence of sleep disorders (insomnia, fatigue, RLS, etc). We detected an overestimation in the RLS questionnaire and the low QoL recorded. Citation: González-Platas M, González-Platas J, Bermúdez-Hernández M, Pérez-Martín MY, Croissier-Elías C, Pérez-Lorensu PJ. Low prevalence of sleep disorders in demyelinating disease in a northern tenerife population. J Clin Sleep

  2. Antibodies to MOG in adults with inflammatory demyelinating disease of the CNS

    PubMed Central

    Woodhall, Mark R.; Kim, Ji-Sun; Kim, Seong-Joon; Park, Kyung Seok; Vincent, Angela; Lee, Kwang-Woo

    2015-01-01

    Objective: To evaluate the clinical relevance of myelin oligodendrocyte glycoprotein antibody (MOG-Ab) in a cohort of adults with inflammatory demyelinating disease (IDD) of the CNS. Methods: Live cell-based assays for MOG-Ab (IgG1 subset) and antibody to aquaporin-4 (AQP4-Ab) were performed in a cohort of 270 adult patients with IDD and 72 controls. Patients were first grouped by positive antibody result as MOG-Ab or AQP4-Ab, and the remainder were grouped by published diagnostic criteria. Results: Seventeen patients with IDD (6.3%) had MOG-Abs and 49 patients (18.1%) had AQP4-Abs; none had both antibodies. The MOG-Ab patients predominantly manifested with isolated symptoms of optic neuritis (83%). One-third of these patients experienced relapses, which involved only the optic nerve, and all relapsed within 1 year of disease onset. At onset, MRI in the MOG-Ab group uniquely demonstrated perineural enhancement, extending to the soft tissues around the optic nerves (33%). Although about 30% of MOG-Ab patients had brain MRI lesions, they had fewer periventricular lesions than the 26 patients with relapsing-remitting multiple sclerosis (MS); none of these lesions were ovoid or perpendicular to the ventricle. Moreover, MOG-Ab patients did not meet the diagnostic criteria for definite neuromyelitis optica (NMO) and had less spinal cord involvement than the AQP4-Ab group. Four patients (23.5%) had poor visual outcomes (<0.2) or paraplegia. Conclusions: MOG-Abs may be a disease-specific biomarker in adult patients with IDD who have a disease distinct from NMO or MS. The radiologic as well as clinical manifestations of MOG-Ab patients can be useful in their differential diagnosis. PMID:26516628

  3. Characteristics of demyelinating Charcot-Marie-Tooth disease with concurrent diabetes mellitus

    PubMed Central

    Yu, Zhiliang; Wu, Xiaohua; Xie, Huijun; Han, Ying; Guan, Yangtai; Qin, Yong; Zheng, Huimin; Jiang, Jianming; Niu, Zhenmin

    2014-01-01

    Purpose: Charcot-Marie-Tooth disease (CMT) is the most common type of inherited peripheral neuropathy and has a high degree of genetic heterogeneity. CMT with concurrent diabetes mellitus (DM) is rare. The purpose of this study is to explore the genetic, clinical and pathological characteristics of the patients with CMT and concurrent DM. Methods: We investigated gene mutations (the peripheral myelin protein 22 gene, myelin protein zero gene, lipopolysaccharide-induced tumor necrosis factor-α factor gene, early growth response gene and the neurofilament light chain gene loci) of a relatively large and typical Chinese family with CMT1 and concurrent DM2. From the literature, we also retrieved all reported families and single cases with CMT and concurrent DM. We comprehensively analyzed the characteristics of total 33 patients with CMT and concurrent DM, and further compared these characteristics with those of patients of diabetic peripheral neuropathy (DPN). Results: Patients with CMT and concurrent DM had some relatively independent characteristics and pathogenic mechanisms. So we designated that kind of characteristic demyelinating CMT which accompanies DM as Yu-Xie syndrome (YXS), a new specific clinical subtype of CMT. Conclusion: CMT is an etiologic factor of DM, even though the intrinsic association between CMT and DM still remains further exploration. PMID:25120817

  4. Viral induced demyelination.

    PubMed

    Stohlman, S A; Hinton, D R

    2001-01-01

    Viral induced demyelination, in both humans and rodent models, has provided unique insights into the cell biology of oligodendroglia, their complex cell-cell interactions and mechanisms of myelin destruction. They illustrate mechanisms of viral persistence, including latent infections in which no infectious virus is readily evident, virus reactivation and viral-induced tissue damage. These studies have also provided excellent paradigms to study the interactions between the immune system and the central nervous system (CNS). Although of interest in their own right, an understanding of the diverse mechanisms used by viruses to induce demyelination may shed light into the etiology and pathogenesis of the common demyelinating disorder multiple sclerosis (MS). This notion is supported by the persistent view that a viral infection acquired during adolescence might initiate MS after a long period of quiescence. Demyelination in both humans and rodents can be initiated by infection with a diverse group of enveloped and non-enveloped RNA and DNA viruses (Table 1). The mechanisms that ultimately result in the loss of CNS myelin appear to be equally diverse as the etiological agents capable of causing diseases which result in demyelination. Although demyelination can be a secondary result of axonal loss, in many examples of viral induced demyelination, myelin loss is primary and associated with axonal sparing. This suggests that demyelination induced by viral infections can result from: 1) a direct viral infection of oligodendroglia resulting in cell death with degeneration of myelin and its subsequent removal; 2) a persistent viral infection, in the presence or absence of infectious virus, resulting in the loss of normal cellular homeostasis and subsequent oligodendroglial death; 3) a vigorous virus-specific inflammatory response wherein the virus replicates in a cell type other than oligodendroglia, but cytokines and other immune mediators directly damage the

  5. Disease Type- and Status-Specific Alteration of CSF Metabolome Coordinated with Clinical Parameters in Inflammatory Demyelinating Diseases of CNS

    PubMed Central

    Kong, Byung Soo; Lee, Jung-Eun; Kim, Kyoung Heon; Lee, Do Yup; Kim, Ho Jin

    2016-01-01

    Central nervous system (CNS) inflammatory demyelinating diseases (IDDs) are a group of disorders with different aetiologies, characterized by inflammatory lesions. These disorders include multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and idiopathic transverse myelitis (ITM). Differential diagnosis of the CNS IDDs still remains challenging due to frequent overlap of clinical and radiological manifestation, leading to increased demands for new biomarker discovery. Since cerebrospinal fluid (CSF) metabolites may reflect the status of CNS tissues and provide an interfacial linkage between blood and CNS tissues, we explored multi-component biomarker for different IDDs from CSF samples using gas chromatography mass spectrometry-based metabolite profiling coupled to multiplex bioinformatics approach. We successfully constructed the single model with multiple metabolite variables in coordinated regression with clinical characteristics, expanded disability status scale, oligoclonal bands, and protein levels. The multi-composite biomarker simultaneously discriminated four different immune statuses (a total of 145 samples; 54 MS, 49 NMOSD, 30 ITM, and 12 normal controls). Furthermore, systematic characterization of transitional metabolic modulation identified relapse-associated metabolites and proposed insights into the disease network underlying type-specific metabolic dysfunctionality. The comparative analysis revealed the lipids, 1-monopalmitin and 1-monostearin were common indicative for MS, NMOSD, and ITM whereas fatty acids were specific for the relapse identified in all types of IDDs. PMID:27855220

  6. Molecular Biology, Epidemiology, and Pathogenesis of Progressive Multifocal Leukoencephalopathy, the JC Virus-Induced Demyelinating Disease of the Human Brain

    PubMed Central

    Ferenczy, Michael W.; Marshall, Leslie J.; Nelson, Christian D. S.; Atwood, Walter J.; Nath, Avindra; Khalili, Kamel

    2012-01-01

    Summary: Progressive multifocal leukoencephalopathy (PML) is a debilitating and frequently fatal central nervous system (CNS) demyelinating disease caused by JC virus (JCV), for which there is currently no effective treatment. Lytic infection of oligodendrocytes in the brain leads to their eventual destruction and progressive demyelination, resulting in multiple foci of lesions in the white matter of the brain. Before the mid-1980s, PML was a relatively rare disease, reported to occur primarily in those with underlying neoplastic conditions affecting immune function and, more rarely, in allograft recipients receiving immunosuppressive drugs. However, with the onset of the AIDS pandemic, the incidence of PML has increased dramatically. Approximately 3 to 5% of HIV-infected individuals will develop PML, which is classified as an AIDS-defining illness. In addition, the recent advent of humanized monoclonal antibody therapy for the treatment of autoimmune inflammatory diseases such as multiple sclerosis (MS) and Crohn's disease has also led to an increased risk of PML as a side effect of immunotherapy. Thus, the study of JCV and the elucidation of the underlying causes of PML are important and active areas of research that may lead to new insights into immune function and host antiviral defense, as well as to potential new therapies. PMID:22763635

  7. Neoplastic leptomeningeal disease masquerading as central serous retinopathy. A case report.

    PubMed

    Elaraoud, Ibrahim; Suleman, Hanif J; Cikatricis, Peter; Palmer, Helen

    2016-01-01

    A 69-year-old man became aware of people's speech being out of synch with their lip movements alongside persistent headaches, both of which progressively worsened. A few weeks later, he developed progressive and painless visual loss in one eye. Initial neurological evaluation, inflammatory markers and head computed tomography scan were normal. Ophthalmological examination and OCT scan revealed right macular subretinal fluid with choroidal indentation, which prompted urgent further investigations including head MRI revealing extensive leptomeningeal disease. The patient continued to deteriorate and deceased shortly afterwards. This is the first reported case of neoplastic leptomeningeal disease presenting with loss of vision due to choroidal metastasis with localised exudative retinal detachment. Diagnosing neoplastic leptomeningeal disease requires a high index of suspicion from the treating physician. Symptoms may be nonspecific and/or subtle. Combining cerebrospinal fluid cytology from lumbar puncture with contrast-enhanced magnetic resonance imaging of the brain is considered the optimal diagnostic approach.

  8. Early Motor Unit Disease Masquerading as Psychogenic Breathy Dysphonia: A Clinical Case Presentation

    ERIC Educational Resources Information Center

    Aronson, Arnold E.

    1971-01-01

    Presented is a study of a 20-year-old girl with mild, breathy dysphonia, previously diagnosed as psychogenic. In actuality, her voice change was a sign of early myasthenia gravis. It is pointed out that voice changes can be a first and only sign of early neurologic disease. (Author/KW)

  9. Squamous cell carcinoma of the eyelid masquerading as 'malignant' ophthalmopathy of Graves's disease.

    PubMed Central

    Ford, H C; Delahunt, J W; Teague, C A

    1983-01-01

    A patient with Graves's disease is described in whom the periorbital changes of severe ophthalmopathy and iatrogenic Cushing's syndrome delayed the diagnosis of a squamous cell carcinoma of the eyelid. It is suggested that the immunosuppressive therapy which the patient received may have enhanced the growth of a pre-existing malignancy. Images PMID:6688354

  10. Contralateral recurrence of tumefactive demyelination

    PubMed Central

    Guranda, Mihail; Essig, Marco

    2015-01-01

    Tumefactive demyelination refers to large focal demyelinating lesions in the brain, which can be mistaken for malignancy. In some patients, these lesions are monophasic with a self-limited course; however, other patients demonstrate recurrent disease with new tumefactive or non-tumefactive lesions, and a subsequent diagnosis of relapsing-remitting multiple sclerosis is not uncommon. Owing to the limited data available in the literature, many questions about the patterns and prognostic significance of recurrent tumefactive lesions remain unanswered. The current case report involves a patient who recovered from tumefactive demyelination and presented two years later with a new recurrent tumefactive lesion in the contralateral brain. PMID:26427896

  11. [The diagnostic value of electromyography in patients with demyelinating diseases of the nervous system].

    PubMed

    Manovich, Z Kh; Gruzman, G B

    1975-01-01

    The authors used EMG registrations of the reflex potentials in the orbicular ocular muscles appearing in an electrostimulation of the supraorbital nerve. The study included an analysis of the fluctuations of the latent period of the winking reflex in patients with different lesions of the central and peripheral nervous system. The authors were able to show a significant elongation of the latent period in patients with disseminated sclerosis, encephalomyelitis, Guillain-Barre polyradiculoneuritis. In other signs of focal lesions of the brain stem and polyneuropathy the latent period of the winking reflex was near to the normal indices. The authors propose to use this method for the study of the process of demyelinization in the brain stem and for early diagnosis of disseminated sclerosis.

  12. Disease-modifying therapy in multiple sclerosis and chronic inflammatory demyelinating polyradiculoneuropathy: common and divergent current and future strategies

    PubMed Central

    Melzer, N; Meuth, S G

    2014-01-01

    Multiple sclerosis (MS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) represent chronic, autoimmune demyelinating disorders of the central and peripheral nervous system. Although both disorders share some fundamental pathogenic elements, treatments do not provide uniform effects across both disorders. We aim at providing an overview of current and future disease-modifying strategies in these disorders to demonstrate communalities and distinctions. Intravenous immunoglobulins (IVIG) have demonstrated short-and long-term beneficial effects in CIDP but are not effective in MS. Dimethyl fumarate (BG-12), teriflunomide and laquinimod are orally administered immunomodulatory drugs that are already approved or likely to be approved in the near future for the basic therapy of patients with relapsing–remitting MS (RRMS) due to positive results in Phase III clinical trials. However, clinical trials with these drugs in CIDP have not (yet) been initiated. Natalizumab and fingolimod are approved for the treatment of RRMS, and trials to evaluate their safety and efficacy in CIDP are now planned. Alemtuzumab, ocrelizumab and daclizumab respresent monoclonal antibodies in advanced stages of clinical development for their use in RRMS patients. Attempts to study the safety and efficacy of alemtuzumab and B cell-depleting anti-CD20 antibodies, i.e. rituximab, ocrelizumab or ofatumumab, in CIDP patients are currently under way. We provide an overview of the mechanism of action and clinical data available on disease-modifying immunotherapy options for MS and CIDP. Enhanced understanding of the relative effects of therapies in these two disorders may aid rational treatment selection and the development of innovative treatment approaches in the future. PMID:24032475

  13. Acquired versus familial demyelinative neuropathies in children.

    PubMed

    Miller, R G; Gutmann, L; Lewis, R A; Sumner, A J

    1985-01-01

    The electrophysiologic differences between chronic acquired demyelinative neuropathy and the demyelinative form of Charcot-Marie-Tooth disease have recently been reported. The present report extends these observations to include the genetically determined demyelinating neuropathies seen in metachromatic leukodystrophy, Krabbe's leukodystrophy, and Cockayne's syndrome. The electrophysiologic features of metachromatic leukodystrophy (five patients), Krabbe's (four patients), and Cockayne's syndrome (three patients) were all similar. There was uniform slowing of conduction (both in different nerves and in different nerve segments), and conduction block was not seen. These findings are consistent with a uniform degree of demyelination in multiple nerves and throughout the entire length of individual axons. Thus, uniform slowing of nerve conduction constitutes strong evidence for a familial demyelinative neuropathy, as opposed to the multifocal slowing seen in acute and chronic acquired demyelinative neuropathy.

  14. Role of the Programmed Death-1 (PD-1) pathway in regulation of Theiler's murine encephalomyelitis virus-induced demyelinating disease.

    PubMed

    Takizawa, Sho; Kaneyama, Tomoki; Tsugane, Sayaka; Takeichi, Naoya; Yanagisawa, Satoshi; Ichikawa, Motoki; Yagita, Hideo; Kim, Byung S; Koh, Chang-Sung

    2014-09-15

    Programmed death-1 (PD-1) belongs to the CD28 family of co-stimulatory and co-inhibitory molecules and regulates adaptive immunity. This molecule induces the development of regulatory T cells, T cell tolerance, or apoptosis. We examined the role of PD-1 pathway in Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease (TMEV-IDD) mice. Up-regulation of PD-1 and PD-1 ligand-1 (PD-L1) mRNA expression in bone marrow-derived dendritic cells were induced by TMEV infection in vitro. Furthermore, PD-1 and PD-L1 mRNA expression was increased in the spinal cords of the TMEV-infected mice in vivo. Treatment with a blocking monoclonal antibody (mAb) against PD-1, especially during the effector phase, resulted in significant deterioration of the TMEV-IDD both clinically and histologically. Flow cytometric analysis revealed a dramatically increase of CD4(+) T cells producing Th1 cytokines such as IFN-γ and TNF-α in the spinal cord of anti-PD-1 mAb-treated mice. These results indicate that the PD-1 pathway plays a pivotal regulatory role in the development of TMEV-IDD.

  15. Infection with Theiler's murine encephalomyelitis virus directly induces proinflammatory cytokines in primary astrocytes via NF-kappaB activation: potential role for the initiation of demyelinating disease.

    PubMed

    Palma, JoAnn P; Kwon, Daeho; Clipstone, Neil A; Kim, Byung S

    2003-06-01

    Theiler's virus infection in the central nervous system (CNS) induces a demyelinating disease very similar to human multiple sclerosis. We have assessed cytokine gene activation upon Theiler's murine encephalomyelitis virus (TMEV) infection and potential mechanisms in order to delineate the early events in viral infection that lead to immune-mediated demyelinating disease. Infection of SJL/J primary astrocyte cultures induces selective proinflammatory cytokine genes (interleukin-12p40 [IL-12p40], IL-1, IL-6, tumor necrosis factor alpha, and beta interferon [IFN-beta]) important in the innate immune response to infection. We find that TMEV-induced cytokine gene expression is mediated by the NF-kappaB pathway based on the early nuclear NF-kappaB translocation and suppression of cytokine activation in the presence of specific inhibitors of the NF-kappaB pathway. Further studies show this to be partly independent of dsRNA-dependent protein kinase (PKR) and IFN-alpha/beta pathways. Altogether, these results demonstrate that infection of astrocytes and other CNS-resident cells by TMEV provides the early NF-kappaB-mediated signals that directly activate various proinflammatory cytokine genes involved in the initiation and amplification of inflammatory responses in the CNS known to be critical for the development of immune-mediated demyelination.

  16. Lethal acute demyelinization with encephalo-myelitis as a complication of cured Cushing's disease.

    PubMed

    Chevalier, N; Hieronimus, S; Vandenbos, F; Delmont, E; Cua, E; Cherick, F; Paquis, P; Michiels, J-F; Fenichel, P; Brucker-Davis, F

    2010-12-01

    Cushing's disease is usually associated with higher mortality rate, especially from cardiovascular causes. Development or exacerbation of autoimmune or inflammatory diseases is known to occur in patients with hypercortisolism after cure. We report for the first time a 34-year old woman with a psychiatric background, who developed four months after the surgical cure of Cushing's disease an acute disseminated encephalomyelitis (ADEM) presenting initially as a psychiatric illness. We hypothesize that the recent correction of hypercortisolism triggered ADEM and that the atypical presentation, responsible for diagnosis delay, led to the death of this patient.

  17. Tumefactive Demyelinating Lesions in Multiple Sclerosis and Associated Disorders.

    PubMed

    Frederick, Meredith C; Cameron, Michelle H

    2016-03-01

    Tumefactive demyelinating lesions are rare consequences of central nervous system (CNS) idiopathic inflammatory demyelinating diseases. Tumefactive demyelinating lesions pose a diagnostic challenge because they can mimic tumors and abscesses and because they can be caused by a heterogeneous range of disorders. This article reviews the recent literature on the clinical presentation; radiographic features; prognosis; and management of tumefactive demyelinating lesions in multiple sclerosis, acute demyelinating encephalomyelitis, neuromyelitis optica, and the rare variants of multiple sclerosis including Schilder's disease, Marburg acute multiple sclerosis, and Balo's concentric sclerosis.

  18. Primary Cutaneous Plasmacytosis: Masquerading as Hidradenitis Suppurativa

    PubMed Central

    Goyal, Tarang; Varshney, Anupam; Zawar, Vijay; Sharma, Veena

    2016-01-01

    Isolated cutaneous plasmacytosis (CP) is a rare entity with few cases reported in world literature. CP masquerading as hidradenitis suppurativa like presentation is a unique case with some features differentiating it clinically from it which were further confirmed by histopathology and immunostaining. Our case showed hyperplasia of mature plasma cells and polyclonal hypergammaglobulinemia, immunostaining for CD138 positivity and kappa: lambda ratio more than 3:1. Extensive clinical and laboratory investigations failed to reveal any underlying pathology, presence of any underlying disease accompanying the hypergammaglobulinemia and/or plasma cell proliferation. PMID:27057027

  19. Acquired inflammatory demyelinating neuropathies.

    PubMed

    Ensrud, E R; Krivickas, L S

    2001-05-01

    The acquired demyelinating neuropathies can be divided into those with an acute onset and course and those with a more chronic course. The acute neuropathies present as Guillain-Barré syndrome and include acute inflammatory demyelinating polyradiculoneuropathy (AIDP), Miller Fisher syndrome, acute motor axonal neuropathy (AMAN), acute motor and sensory axonal neuropathy (AMSAN), and acute pandysautonomia. The chronic neuropathies are collectively known as chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and include MADSAM (multifocal acquired demyelinating sensory and motor neuropathy, also know as Lewis-Sumner syndrome) and DADS (distal acquired demyelinating symmetric neuropathy) as variants. The clinical features, pathology, pathogenesis, diagnosis, treatment, rehabilitation, and prognosis of these neuropathies are discussed.

  20. TNFR2 Deficiency Acts in Concert with Gut Microbiota To Precipitate Spontaneous Sex-Biased Central Nervous System Demyelinating Autoimmune Disease.

    PubMed

    Miller, Patrick G; Bonn, Michael B; Franklin, Craig L; Ericsson, Aaron C; McKarns, Susan C

    2015-11-15

    TNF-α antagonists provide benefit to patients with inflammatory autoimmune disorders such as Crohn's disease, rheumatoid arthritis, and ankylosing spondylitis. However, TNF antagonism unexplainably exacerbates CNS autoimmunity, including multiple sclerosis and neuromyelitis optica. The underlying mechanisms remain enigmatic. We demonstrate that TNFR2 deficiency results in female-biased spontaneous autoimmune CNS demyelination in myelin oligodendrocyte glycoprotein-specific 2D2 TCR transgenic mice. Disease in TNFR2(-/-) 2D2 mice was associated with CNS infiltration of T and B cells as well as increased production of myelin oligodendrocyte glycoprotein-specific IL-17, IFN-γ, and IgG2b. Attenuated disease in TNF(-/-) 2D2 mice relative to TNFR2(-/-) 2D2 mice identified distinctive roles for TNFR1 and TNFR2. Oral antibiotic treatment eliminated spontaneous autoimmunity in TNFR2(-/-) 2D2 mice to suggest role for gut microbiota. Illumina sequencing of fecal 16S rRNA identified a distinct microbiota profile in male TNFR2(-/-) 2D2 that was associated with disease protection. Akkermansia muciniphila, Sutterella sp., Oscillospira sp., Bacteroides acidifaciens, and Anaeroplasma sp. were selectively more abundant in male TNFR2(-/-) 2D2 mice. In contrast, Bacteroides sp., Bacteroides uniformis, and Parabacteroides sp. were more abundant in affected female TNFR2(-/-) 2D2 mice, suggesting a role in disease causation. Overall, TNFR2 blockade appears to disrupt commensal bacteria-host immune symbiosis to reveal autoimmune demyelination in genetically susceptible mice. Under this paradigm, microbes likely contribute to an individual's response to anti-TNF therapy. This model provides a foundation for host immune-microbiota-directed measures for the prevention and treatment of CNS-demyelinating autoimmune disorders.

  1. Temporal dynamics of anti-MOG antibodies in CNS demyelinating diseases.

    PubMed

    Di Pauli, Franziska; Mader, Simone; Rostasy, Kevin; Schanda, Kathrin; Bajer-Kornek, Barbara; Ehling, Rainer; Deisenhammer, Florian; Reindl, Markus; Berger, Thomas

    2011-03-01

    Recent studies demonstrated the presence of autoantibodies to native myelin oligodendrocyte glycoprotein (MOG) in juvenile patients with acute disseminated encephalomyelitis (ADEM) and multiple sclerosis (MS). However, so far no longitudinal studies on anti-MOG antibodies have been performed. Therefore, we determined serum and CSF antibodies against native human MOG in 266 pediatric and adult subjects with ADEM, clinically isolated syndrome (CIS), MS, other neurological diseases (OND) and healthy controls (HC) and longitudinal samples of 25 patients with ADEM, CIS, MS and OND using an immunofluorescence assay. We detected serum high-titer MOG IgG in 15/34 (44%) patients with ADEM, but only rarely in CIS (3/38, 8%), MS (2/89, 2%), OND (1/58, 2%) and HC (0/47). Longitudinal analysis of serum anti-MOG IgG showed different temporal dynamics of serum antibody responses in ADEM, CIS and MS and indicated an association of a favorable clinical outcome in ADEM with a decrease in antibody titers over time.

  2. Immunological reaction of the demyelinating Semliki Forest virus with immune serum to glycolipids and its possible importance to central nervous system viral auto-immune disease.

    PubMed

    Webb, H E; Mehta, S; Gregson, N A; Leibowitz, S

    1984-01-01

    The avirulent demyelinating strain A7(74) of Semliki Forest virus after passage through mouse brain in vivo and mouse brain cell cultures has been shown to react immunologically with immune sera against galactocerebroside, glucocerebroside, total ganglioside and GT1b ganglioside but not against myelin or sulphatide . Semliki Forest virus is known to take host membrane glycolipid into its coat. The importance of the findings is discussed in relation to the production of a possible anti-brain cell auto-immune phenomenon and its implication in a disease such as multiple sclerosis.

  3. Chronic Inflammatory Demyelinating Polyneuropathy

    PubMed Central

    Dimachkie, Mazen M.; Barohn, Richard J.

    2014-01-01

    Opinion statement Chronic Inflammatory polyneuropathies are an important group of neuromuscular disorders that present chronically and progress over more than 8 weeks, being referred to as chronic inflammatory demyelinating polyneuropathy (CIDP). Despite tremendous progress in elucidating disease pathogenesis, the exact triggering event remains unknown. Our knowledge regarding diagnosis and management of CIDP and its variants continues to expand, resulting in improved opportunities for identification and treatment. Most clinical neurologists will be involved in the management of patients with these disorders, and should be familiar with available therapies for CIDP. We review the distinctive clinical, laboratory, and electro-diagnostic features that aid in diagnosis. We emphasize the importance of clinical patterns that define treatment responsiveness and the most appropriate therapies in order to improve prognosis. PMID:23564314

  4. The Oligodendrocyte Progenitor Response to Demyelination

    DTIC Science & Technology

    2006-01-01

    Chapter 2 : Myelin Transcription Factor 1 (Myt1) Expression in Demyelinated Lesions of Rodent and Human CNS 13-50 Chapter 3: Platelet-derived...yield these much sought after therapeutics for such debilitating diseases as MS. 14 CHAPTER 2 Myelin Transcription Factor 1 (Myt1) Expression...in Demyelinated Lesions of Rodent and Human CNS Adam C. Vana 1,2 , Claudia F. Lucchinetti. 3 , Tuan Q. Le 2 , and Regina C. Armstrong 1,2,4 1

  5. Hypoxia Inducible Factor-1α in Astrocytes and/or Myeloid Cells Is Not Required for the Development of Autoimmune Demyelinating Disease1,2,3

    PubMed Central

    Le Moan, Natacha; Baeten, Kim M.; Rafalski, Victoria A.; Kyu Ryu, Jae; Rios Coronado, Pamela E.; Bedard, Catherine; Syme, Catriona; Davalos, Dimitrios

    2015-01-01

    Abstract Hypoxia-like tissue alterations, characterized by the upregulation of hypoxia-inducible factor-1α (HIF-1α), have been described in the normal appearing white matter and pre-demyelinating lesions of multiple sclerosis (MS) patients. As HIF-1α regulates the transcription of a wide set of genes involved in neuroprotection and neuroinflammation, HIF-1α expression may contribute to the pathogenesis of inflammatory demyelination. To test this hypothesis, we analyzed the effect of cell-specific genetic ablation or overexpression of HIF-1α on the onset and progression of experimental autoimmune encephalomyelitis (EAE), a mouse model for MS. HIF-1α was mainly expressed in astrocytes and microglia/macrophages in the mouse spinal cord at the peak of EAE. However, genetic ablation of HIF-1α in astrocytes and/or myeloid cells did not ameliorate clinical symptoms. Furthermore, conditional knock-out of Von Hippel Lindau, a negative regulator of HIF-1α stabilization, failed to exacerbate the clinical course of EAE. In accordance with clinical symptoms, genetic ablation or overexpression of HIF-1α did not change the extent of spinal cord inflammation and demyelination. Overall, our data indicate that despite dramatic upregulation of HIF-1α in astrocytes and myeloid cells in EAE, HIF-1α expression in these two cell types is not required for the development of inflammatory demyelination. Despite numerous reports indicating HIF-1α expression in glia, neurons, and inflammatory cells in the CNS of MS patients, the cell-specific contribution of HIF-1α to disease pathogenesis remains unclear. Here we show that although HIF-1α is dramatically upregulated in astrocytes and myeloid cells in EAE, cell-specific depletion of HIF-1α in these two cell types surprisingly does not affect the development of neuroinflammatory disease. Together with two recently published studies showing a role for oligodendrocyte-specific HIF-1α in myelination and T-cell-specific HIF-1α in

  6. [Autopsy case of a patient with Charcot-Marie-Tooth disease type 1A and suspected chronic inflammatory demyelinating polyradiculoneuropathy, which was later diagnosed as amyotrophic lateral sclerosis].

    PubMed

    Higuchi, Yujiro; Sakiyama, Yusuke; Nishihira, Yasushi; Endo, Kazuhiro; Suwazono, Shugo; Suehara, Masahito

    2012-01-01

    We report an autopsy case of a 74-year-old man with late onset Charcot-Marie-Tooth disease type 1A (CMT1A) diagnosed by genetic screening, later associated with amyotrophic lateral sclerosis (ALS). At the age of 70 years, the patient was admitted to our hospital because of progressive weakness and dysesthesia in the right upper limb. In the early stages of the illness, he was diagnosed with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and transient improvement was achieved with intravenous immunoglobulin. However, the symptoms progressively worsened and became refractory. Gene analysis revealed PMP22 gene duplication, which confirmed CMT1A. On sural nerve biopsy, severe demyelinating neuropathy and abundant onion-bulb formations with endoneurial infiltration of inflammatory cells were observed. Thereafter, pseudo-bulbar palsy and respiratory muscle weakness developed insidiously and progressed rapidly along with muscle weakness in the limbs and trunk. The patient died about four years after the onset of this disease. Postmortem examination showed moderate neuronal cell loss, Bunina bodies, and TDP-43-positive inclusions in the anterior horn cells. The spinal cord revealed axonal loss and extensive macrophage permeation in the corticospinal tracts. On the basis of these findings, the final neuropathological diagnosis was ALS. This is the first report of an autopsy case of CMT1A complicated with ALS. We here discuss the significant clinical and neuropathological findings of this case.

  7. Terminal Ileitis as a Feature of Henoch-Schönlein Purpura Masquerading as Crohn Disease in Adults.

    PubMed

    Sampat, Hemal N; McAllister, Brian P; Gaines, Darryl D; Ostrov, Barbara

    2016-03-01

    Henoch-Schönlein purpura (HSP), more recently termed immunoglobulin A (IgA) vasculitis, is a systemic small-vessel vasculitis characterized by perivascular IgA deposition. This disease manifests clinically as palpable purpura, arthralgia, gastrointestinal symptoms, and renal dysfunction. Although ileitis can be seen in HSP, terminal ileitis is virtually pathognomonic for Crohn disease. We present a comprehensive review of the literature on this association, including 2 cases of our own, to demonstrate the importance of considering HSP in the differential diagnosis of ileitis suggestive of Crohn disease. We review the growing body of literature suggesting a pathophysiologic link between the conditions, possibly through an IgA-mediated mechanism.

  8. Acute Monocytic Leukemia Masquerading Behçet's Disease-Like Illness at Onset in an Elderly Female

    PubMed Central

    Koba, Shigeru; Sekioka, Toshio; Takeda, Sorou; Miyagawa-Hayashino, Aya; Nishimura, Keisuke

    2016-01-01

    A previously healthy 74-year-old Japanese female was hospitalized with fever and high C-reactive protein. She developed palatal herpangina-like aphthous ulcers, localized intestinal wall thickening, terminal ileum ulcers, and an erythematous acneiform rash; thus Behçet's disease-like illness was suspected. Significant peripheral blood acute monocytosis developed during her hospitalization and acute monocytic leukemia (FAB M5b) with normal karyotype was diagnosed. By immunostaining, the infiltrating cells in the skin and the terminal ileum were identified as monocytic leukemic cells. This case exhibited a unique initial presentation of Behçet's disease-like illness associated with acute monocytic leukemia. PMID:27610252

  9. The electrodiagnostic distinctions between chronic familial and acquired demyelinative neuropathies.

    PubMed

    Lewis, R A; Sumner, A J

    1982-06-01

    We compared the electrodiagnostic studies of 40 patients with chronic acquired demyelinative neuropathy and 18 patients with familial demyelinative neuropathy. Patients with acquired neuropathy had differential slowing of conduction velocity when distal latencies were compared with more proximal conduction velocities in the same nerve, when equivalent segments of different nerves were compared, and when dispersion of compound motor action potentials was examined. Conduction block was noted in some patients. Patients with familial disease had uniform conduction slowly of all nerve segments, and conduction block was not seen. Chronic acquired demyelinative neuropathy is characterized by multifocal slowing of nerve conduction, whereas familial demyelinative neuropathy is characterized by uniform conduction slowing.

  10. Pyoderma gangrenosum masquerading as Donovanosis

    PubMed Central

    Pai, Varadraj V.; Kikkeri, Naveen Narayanshetty; Athanikar, S. B.; Myageri, Anil; Rai, Vijetha

    2014-01-01

    Pyoderma gangrenosum (PG) is a rare inflammatory disorder of unknown etiology characterized by neutrophilic infiltration of the dermis and destruction of tissue. PG is diagnosed after excluding more commonly occurring condition presenting with similar manifestation. Though PG has been reported to occur over the genitalia, it rarely presents with concurrent involvement of the groin. Herein, we present a case of PG masquerading as Donovanosis. PMID:26396454

  11. 22q11.2q13 duplication including SOX10 causes sex-reversal and peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, Waardenburg syndrome, and Hirschsprung disease.

    PubMed

    Falah, Nadia; Posey, Jennifer E; Thorson, Willa; Benke, Paul; Tekin, Mustafa; Tarshish, Brocha; Lupski, James R; Harel, Tamar

    2017-04-01

    Diagnosis of genetic syndromes may be difficult when specific components of a disorder manifest at a later age. We present a follow up of a previous report [Seeherunvong et al., (2004); AJMGA 127: 149-151], of an individual with 22q duplication and sex-reversal syndrome. The subject's phenotype evolved to include peripheral and central demyelination, Waardenburg syndrome type IV, and Hirschsprung disease (PCWH; MIM 609136). DNA microarray analysis defined the duplication at 22q11.2q13, including SOX10. Sequencing of the coding region of SOX10 did not reveal any mutations. Our data suggest that SOX10 duplication can cause disorders of sex development and PCWH, supporting the hypothesis that SOX10 toxic gain of function rather than dominant negative activity underlies PCWH.

  12. Chronic inflammatory demyelinating polyneuropathy.

    PubMed

    Vanasse, Michel; Rossignol, Elsa; Hadad, Elie

    2013-01-01

    Chronic inflammatory demyelinating polyneuropathy (CIDP) is characterized clinically by a progressive symmetrical weakness evolving over a period of at least 2 months. There is increased CSF protein and conduction block, reduced nerve conduction velocities, increased distal latencies, and/or absent F wave or prolonged F wave latency in two or more nerves. Incidence is lower in children (10 times less) than in adults, and the condition presents in an acute or subacute manner with frequent relapses. It is not associated with other systemic diseases such as neoplasia, diabetes mellitus, or monoclonal gammopathies. It appears to be immune-related as a variety of humoral and cellular autoimmune mechanisms have been implicated. Treatment is based on results obtained in randomized clinical trials (RCTs) conducted in adults as such studies are lacking in the pediatric population. The evolution of CIDP is more favorable in children than in adults, with 80-100% response rates to standard treatments (steroids, intravenous immunoglobulins, and/or plasmapheresis) and excellent outcome with complete functional recovery in most patients. Cases refractory to standard therapies do exist in children, for which azathioprine, methotrexate, and mycophenolate mofetil alone or more often in association with other treatments have been used. However, safety and efficacy data are still insufficient to give specific recommendations regarding the optimal choice.

  13. Molecular Disruptions of the Panglial Syncytium Block Potassium Siphoning and Axonal Saltatory Conduction: Pertinence to Neuromyelitis Optica and other Demyelinating Diseases of the Central Nervous System

    PubMed Central

    Rash, John E.

    2009-01-01

    The panglial syncytium maintains ionic conditions required for normal neuronal electrical activity in the central nervous system (CNS). Vital among these homeostatic functions is “potassium siphoning”, a process originally proposed to explain astrocytic sequestration and long-distance disposal of K+ released from unmyelinated axons during each action potential. Fundamentally different, more efficient processes are required in myelinated axons, where axonal K+ efflux occurs exclusively beneath and enclosed within the myelin sheath, precluding direct sequestration of K+ by nearby astrocytes. Molecular mechanisms for entry of excess K+ and obligatorily-associated osmotic water from axons into innermost myelin are not well characterized, whereas at the output end, axonally-derived K+ and associated osmotic water are known to be expelled by Kir4.1 and aquaporin-4 channels concentrated in astrocyte endfeet that surround capillaries and that form the glia limitans. Between myelin (input end) and astrocyte endfeet (output end) is a vast network of astrocyte “intermediaries” that are strongly inter-linked, including with myelin, by abundant gap junctions that disperse excess K+ and water throughout the panglial syncytium, thereby greatly reducing K+-induced osmotic swelling of myelin. Here, I review original reports that established the concept of potassium siphoning in unmyelinated CNS axons, summarize recent revolutions in our understanding of K+ efflux during axonal saltatory conduction, then describe additional components required by myelinated axons for a newly-described process of voltage-augmented “dynamic” potassium siphoning. If any of several molecular components of the panglial syncytium are compromised, K+ siphoning is blocked, myelin is destroyed, and axonal saltatory conduction ceases. Thus, a common thread linking several CNS demyelinating diseases is the disruption of potassium siphoning/water transport within the panglial syncytium. Continued

  14. The immune response in the CNS in Theiler's virus induced demyelinating disease switches from an early adaptive response to a chronic innate-like response.

    PubMed

    Gilli, Francesca; Li, Libin; Pachner, Andrew R

    2016-02-01

    Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD) is an important model of the progressive disability caused by irreversible CNS tissue injury, and provides an example of how a CNS pathogen can cause inflammation, demyelination, and neuronal damage. We were interested in which molecules, especially inflammatory mediators, might be upregulated in the CNS throughout TMEV-IDD. We quantitated by a real-time RT-PCR multi-gene system the expression of a pathway-focused panel of genes at 30 and 165 days post infection, characterizing both the early inflammatory and the late neurodegenerative stages of TMEV-IDD. Also, we measured 32 cytokines/chemokines by multiplex Luminex analysis in CSF specimens from early and late TMEV-IDD as well as sham-treated mice. Results indicate that, in the later stage of TMEV-IDD, activation of the innate immune response is most prominent: TLRs, type I IFN response genes, and innate immunity-associated cytokines were highly expressed in late TMEV-IDD compared to sham (p ≤ 0.0001) and early TMEV-IDD (p < 0.05). Conversely, several molecular mediators of adaptive immune response were highly expressed in early TMEV-IDD (all p ≤ 0.001). Protein detection in the CSF was broadly concordant with mRNA abundance of the corresponding gene measured by real-time RT-PCR in the spinal cord, since several cytokines/chemokines were increased in the CSF of TMEV-IDD mice. Results show a clear shift from adaptive to innate immunity from early to late TMEV-IDD, indicating that adaptive and innate immune pathways are likely involved in the development and progression of the disease to different extents. CSF provides an optimal source of biomarkers of CNS neuroinflammation.

  15. Characterization of variations in IL23A and IL23R genes: possible roles in multiple sclerosis and other neuroinflammatory demyelinating diseases

    PubMed Central

    Yan, Peng; Jin, Mei-Hua; Yue, Hui; Zhang, Qiong; Fu, Jin; Liu, Shu-Lin

    2016-01-01

    Multiple sclerosis is among the most serious inflammatory demyelinating diseases (IDD). Interleukin-23A (IL23A) regulates and coordinates the activities of immune cells by interacting with its receptor IL23R and plays key roles in the pathogenesis of immune inflammatory diseases. IDD, deemed to be a kind of autoimmune diseases, may involve IL23A in the pathogenesis. The aim of this work was to validate the hypothesized involvement of IL-23A and its receptor in IDD. We sequenced the IL-23A and IL-23R genes for 206 Chinese Han IDD patients and evaluated SNPs within or near those genes. The serum levels of IL23A in IDD participants were analyzed using ELISA. The statistical analyses were conducted using Chi-Square Tests as implemented in SPSS (version 19.0). The Hardy-Weinberg equilibrium test of the population was carried out using online software OEGE. Three variants rs2066808, rs2371494, rs11575248 in IL-23A gene and one variant rs1884444 in IL-23R gene were demonstrated to be associated with the risk of MS or other IDD diseases, and the expression level of serum IL-23A in the MS patients was also altered. We conclude that variants in IL-23A and IL-23R genes were associated with the risk of MS or other IDD diseases. PMID:27893410

  16. Chronic inflammatory demyelinating polyneuropathy.

    PubMed

    Gorson, Kenneth C; Katz, Jonathan

    2013-05-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an immune disorder of the peripheral nervous system. This article highlights our current understanding of the condition along with its phenotypic variants that are encountered in clinical practice. The diagnostic evaluation of CIDP includes laboratory studies to detect associated medical conditions and electrodiagnostic studies to assess for demyelination. Current treatment options include corticosteroids, plasma exchange, and intravenous immune globulin, along with alternative therapies that may be used as corticosteroid-sparing agents or for treatment-refractory cases. Approximately 85% to 90% of patients eventually improve or stabilize with treatment, and the long-term prognosis of CIDP is favorable.

  17. Early identification of 'acute-onset' chronic inflammatory demyelinating polyneuropathy.

    PubMed

    Sung, Jia-Ying; Tani, Jowy; Park, Susanna B; Kiernan, Matthew C; Lin, Cindy Shin-Yi

    2014-08-01

    Distinguishing patients with acute-onset chronic inflammatory demyelinating polyneuropathy from acute inflammatory demyelinating polyneuropathy prior to relapse is often challenging at the onset of their clinical presentation. In the present study, nerve excitability tests were used in conjunction with the clinical phenotype and disease staging, to differentiate between patients with acute-onset chronic inflammatory demyelinating polyneuropathy and patients with acute inflammatory demyelinating polyneuropathy at an early stage, with the aim to better guide treatment. Clinical assessment, staging and nerve excitability tests were undertaken on patients initially fulfilling the diagnostic criteria of acute inflammatory demyelinating polyneuropathy soon after symptom onset and their initial presentation. Patients were subsequently followed up for minimum of 12 months to determine if their clinical presentations were more consistent with acute-onset chronic inflammatory demyelinating polyneuropathy. Clinical severity as evaluated by Medical Research Council sum score and Hughes functional grading scale were not significantly different between the two cohorts. There was no difference between the time of onset of initial symptoms and nerve excitability test assessment between the two cohorts nor were there significant differences in conventional nerve conduction study parameters. However, nerve excitability test profiles obtained from patients with acute inflammatory demyelinating polyneuropathy demonstrated abnormalities in the recovery cycle of excitability, including significantly reduced superexcitability (P < 0.001) and prolonged relative refractory period (P < 0.01), without changes in threshold electrotonus. In contrast, in patients with acute-onset chronic inflammatory demyelinating polyneuropathy, a different pattern occurred with the recovery cycle shifted downward (increased superexcitability, P < 0.05; decreased subexcitability, P < 0.05) and increased

  18. A Case of Cauda Equina Syndrome in Early-Onset Chronic Inflammatory Demyelinating Polyneuropathy Clinically Similar to Charcot-Marie-Tooth Disease Type 1

    PubMed Central

    Lee, Seung Eun; Ha, Sam Yeol; Nam, Taek Kyun

    2014-01-01

    To present a case of cauda equina syndrome (CES) caused by chronic inflammatory demyelinating polyneuropathy (CIDP) which seemed clinically similar to Charcot-Marie-Tooth disease type1 (CMT1). CIDP is an immune-mediated polyneuropathy, either progressive or relapsing-remitting. It is a non-hereditary disorder characterized by symmetrical motor and sensory deficits. Rarely, spinal nerve roots can be involved, leading to CES by hypertrophic cauda equina. A 34-year-old man presented with low back pain, radicular pain, bilateral lower-extremity weakness, urinary incontinence, and constipation. He had had musculoskeletal deformities, such as hammertoes and pes cavus, since age 10. Lumbar spine magnetic resonance imaging showed diffuse thickening of the cauda equina. Electrophysiological testing showed increased distal latency, conduction blocks, temporal dispersion, and severe nerve conduction velocity slowing (3 m/s). We were not able to find genetic mutations at the PMP 22, MPZ, PRX, and EGR2 genes. The pathologic findings of the sural nerve biopsy revealed thinly myelinated nerve fibers with Schwann cells proliferation. We performed a decompressive laminectomy, intravenous IgG (IV-IgG) and oral steroid. At 1 week after surgery, most of his symptoms showed marked improvements except foot deformities. There was no relapse or aggravation of disease for 3 years. We diagnosed the case as an early-onset CIDP with cauda equine syndrome, whose initial clinical findings were similar to those of CMT1, and successfully managed with decompressive laminectomy, IV-IgG and oral steroid. PMID:25237436

  19. Aggregation of MBP in chronic demyelination

    PubMed Central

    Frid, Kati; Einstein, Ofira; Friedman-Levi, Yael; Binyamin, Orli; Ben-Hur, Tamir; Gabizon, Ruth

    2015-01-01

    Objectives Misfolding of key disease proteins to an insoluble state is associated with most neurodegenerative conditions, such as prion, Parkinson, and Alzheimer’s diseases. In this work, and by studying animal models of multiple sclerosis, we asked whether this is also the case for myelin basic protein (MBP) in the late and neurodegenerative phases of demyelinating diseases. Methods To this effect, we tested whether MBP, an essential myelin component, present prion-like properties in animal models of MS, as is the case for Cuprizone-induced chronic demyelination or chronic phases of Experimental Autoimmune Encephalomyelitis (EAE). Results We show here that while total levels of MBP were not reduced following extensive demyelination, part of these molecules accumulated thereafter as aggregates inside oligodendrocytes or around neuronal cells. In chronic EAE, MBP precipitated concomitantly with Tau, a marker of diverse neurodegenerative conditions, including MS. Most important, analysis of fractions from Triton X-100 floatation gradients suggest that the lipid composition of brain membranes in chronic EAE differs significantly from that of naïve mice, an effect which may relate to oxidative insults and subsequently prevent the appropriate insertion and compaction of new MBP in the myelin sheath, thereby causing its misfolding and aggregation. Interpretation Prion-like aggregation of MBP following chronic demyelination may result from an aberrant lipid composition accompanying this pathological status. Such aggregation of MBP may contribute to neuronal damage that occurs in the progressive phase of MS. PMID:26273684

  20. Masquerading Bundle Branch Block: A Poor Prognostic Sign Revisited

    PubMed Central

    Dhanse, Suheil; Kareem, Hashir; Devasia, Tom

    2016-01-01

    Masquerading bundle branch block is a rare but important finding on the Electrocardiogram (ECG). It is an indication of severe and diffuse conduction system disease and usually indicates poor prognosis. The precordial leads show a Right Bundle Branch Block (RBBB) pattern while the limb leads resemble a Left Bundle Branch Block (LBBB). This finding on an ECG is almost invariably associated with severe underlying heart disease. It is extremely important to be aware of this finding as it is a marker of poor cardiac outcomes. We report the case of a 68-year-old gentleman, who presented with progressive dyspnoea on exertion over three months. ECG showed a broad QRS complex with a RBBB pattern on the precordial leads and a LBBB pattern on the limb leads (suggestive of masquerading bundle branch block). A coronary angiogram revealed severe Triple Vessel Disease (TVD). The patient was scheduled for an early Coronary Artery By-Pass Grafting Surgery. However, his clinical condition deteriorated and he died while awaiting the surgery. PMID:27790494

  1. Mitochondrial immobilization mediated by syntaphilin facilitates survival of demyelinated axons

    PubMed Central

    Ohno, Nobuhiko; Chiang, Hao; Mahad, Don J.; Kidd, Grahame J.; Liu, LiPing; Ransohoff, Richard M.; Sheng, Zu-Hang; Komuro, Hitoshi; Trapp, Bruce D.

    2014-01-01

    Axonal degeneration is a primary cause of permanent neurological disability in individuals with the CNS demyelinating disease multiple sclerosis. Dysfunction of axonal mitochondria and imbalanced energy demand and supply are implicated in degeneration of chronically demyelinated axons. The purpose of this study was to define the roles of mitochondrial volume and distribution in axonal degeneration following acute CNS demyelination. We show that the axonal mitochondrial volume increase following acute demyelination of WT CNS axons does not occur in demyelinated axons deficient in syntaphilin, an axonal molecule that immobilizes stationary mitochondria to microtubules. These findings were supported by time-lapse imaging of WT and syntaphilin-deficient axons in vitro. When demyelinated, axons deficient in syntaphilin degenerate at a significantly greater rate than WT axons, and this degeneration can be rescued by reducing axonal electrical activity with the Na+ channel blocker flecainide. These results support the concept that syntaphilin-mediated immobilization of mitochondria to microtubules is required for the volume increase of axonal mitochondria following acute demyelination and protects against axonal degeneration in the CNS. PMID:24958879

  2. Demyelination in canine distemper virus infection: a review.

    PubMed

    Vandevelde, Marc; Zurbriggen, Andreas

    2005-01-01

    Canine distemper virus (CDV) causes severe immunosuppression and neurological disease in dogs, associated with demyelination, and is a model for multiple sclerosis in man. In the early stage of the infection, demyelination is associated with viral replication in the white matter. In acute demyelinating lesions there is massive down-regulation of myelin transcription and metabolic impairment of the myelin-producing cells, but there is no evidence that these cells are undergoing apoptosis or necrosis. Oligodendroglial change is related to restricted infection of these cells (transcription but no translation) and marked activation of microglial cells in acute lesions. Concomitant with immunological recovery during the further course of the disease, inflammation occurs in the demyelinating plaques with progression of the lesions in some animals. A series of experiments in vitro suggests that chronic inflammatory demyelination is due to a bystander mechanism resulting from interactions between macrophages and antiviral antibodies. Autoimmune reactions are also observed, but do not correlate with the course of the disease. The progressive or relapsing course of the disease is associated with viral persistence in the nervous system. Persistence of CDV in the brain appears to be favored by non-cytolytic selective spread of the virus and restricted infection, in this way escaping immune surveillance in the CNS. The CDV Fusion protein appears to play an important role in CDV persistence. Similarities between canine distemper and rodent models of virus-induced demyelination are discussed.

  3. The Prevalence of Anti-Aquaporin 4 Antibody in Patients with Idiopathic Inflammatory Demyelinating Diseases Presented to a Tertiary Hospital in Malaysia: Presentation and Prognosis

    PubMed Central

    Tan, C. T.

    2017-01-01

    Background. There have been inconsistent reports on the prevalence and pathogenicity of anti-Aquaporin 4 (AQP4) in patients presented with idiopathic inflammatory demyelinating diseases (IIDDs). Objective. To estimate the prevalence of anti-AQP4 antibody in patients with IIDDs presented to University Malaya Medical Centre in terms of patients' clinical and radiological presentations and prognoses. Methods. Retrospective data review of IIDDs patients presented from 2005 to 2015. Patients were classified into classical multiple sclerosis (CMS), opticospinal (OS) presentation, optic neuritis (ON), transverse myelitis (TM), brainstem syndrome (BS), and tumefactive MS. Anti-Aquaporin 4 antibody was tested using the Indirect Immunofluorescence Test (IIFT) cell-based assay. Statistical analysis was done using the SPSS version 20. Results. Anti-AQP4 antibody was detected in 53% of patients presented with IIDDs. CMS was more common in the seronegative group, 27/47 (57.45%; p < 0.001). Conversely, OS involvement was more common in the seropositive group, 26/53 (49.06%; p < 0.001). Longitudinally extensive spinal cord lesions (LESCLs) on MRI were also more common in the seropositive group, 29/40 (72.50%; p = 0.004). Only 2/40 (5.00%) had MRI evidence of patchy or multiple short-segment spinal cord lesions in the AQP4-positive group (p = 0.003). The relapse rate and Expanded Disability Status Scale (EDSS) were also higher in the seropositive group (5.43 versus 3.17, p = 0.005; 4.07 versus 2.51, p = 0.006, resp.). Typical clinical presentations that defined NMO were also seen in the seronegative patients, but in a lower frequency. Conclusion. Our cohort of patients had a higher prevalence of seropositivity of anti-AQP4 antibody as compared to those in Western countries. This was also associated with a more typical presentation of opticospinal involvement with LESCLs on MRI, a higher rate of relapse, and EDSS. PMID:28203460

  4. Initial analysis of non-typical Leber hereditary optic neuropathy (LHON) at onset and late developing demyelinating disease in Italian patients by SSCP and automated DNA sequence analysis

    SciTech Connect

    Sartore, M.; Semeraro, A.; Fortina, P.

    1994-09-01

    LHON is a mitochondrial genetic disease characterized by maternal inheritance and late onset of blindness caused by bilateral retinal degeneration. A number of molecular defects are known affecting expression of seven mitochondrial genes encoding subunits of respiratory chain complex I, III and IV. We screened genomic DNA from Italian patients for seven of the known point mutations in the ND-1, ND-4 and ND-6 subunits of complex I by PCR followed by SSCP and restriction enzyme digestion. Most of the patients had nonfamilial bilateral visual loss with partial or no recovery and normal neurological examination. Fundoscopic examination revealed that none of the patients had features typical of LHON. Nine of 21 patients (43%) showed multifocal CNS demyelination on MRI. Our results show aberrant SSCP patterns for a PCR product from the ND-4 subunit in one affected child and his mother. Sfa NI and Mae III digestions suggested the absence of a previously defined LHON mutation, and automated DNA sequence analysis revealed two A to G neutral sequence polymorphisms in the third position of codons 351 and 353. In addition, PCR products from the same two samples and an unrelated one showed abnormal SSCP patterns for the ND-1 subunit region of complex I due to the presence of a T to C change at nt 4,216 which was demonstrated after Nla III digestion of PCR products and further confirmed by DNA sequence analysis. Our results indicate that additional defects are present in the Italian population, and identification of abnormal SSCP patterns followed by targeted automated DNA sequence analysis is a reasonable strategy for delineation of new LHON mutations.

  5. Transcriptional Changes in Canine Distemper Virus-Induced Demyelinating Leukoencephalitis Favor a Biphasic Mode of Demyelination

    PubMed Central

    Ulrich, Reiner; Puff, Christina; Wewetzer, Konstantin; Kalkuhl, Arno; Deschl, Ulrich; Baumgärtner, Wolfgang

    2014-01-01

    Canine distemper virus (CDV)-induced demyelinating leukoencephalitis in dogs (Canis familiaris) is suggested to represent a naturally occurring translational model for subacute sclerosing panencephalitis and multiple sclerosis in humans. The aim of this study was a hypothesis-free microarray analysis of the transcriptional changes within cerebellar specimens of five cases of acute, six cases of subacute demyelinating, and three cases of chronic demyelinating and inflammatory CDV leukoencephalitis as compared to twelve non-infected control dogs. Frozen cerebellar specimens were used for analysis of histopathological changes including demyelination, transcriptional changes employing microarrays, and presence of CDV nucleoprotein RNA and protein using microarrays, RT-qPCR and immunohistochemistry. Microarray analysis revealed 780 differentially expressed probe sets. The dominating change was an up-regulation of genes related to the innate and the humoral immune response, and less distinct the cytotoxic T-cell-mediated immune response in all subtypes of CDV leukoencephalitis as compared to controls. Multiple myelin genes including myelin basic protein and proteolipid protein displayed a selective down-regulation in subacute CDV leukoencephalitis, suggestive of an oligodendrocyte dystrophy. In contrast, a marked up-regulation of multiple immunoglobulin-like expressed sequence tags and the delta polypeptide of the CD3 antigen was observed in chronic CDV leukoencephalitis, in agreement with the hypothesis of an immune-mediated demyelination in the late inflammatory phase of the disease. Analysis of pathways intimately linked to demyelination as determined by morphometry employing correlation-based Gene Set Enrichment Analysis highlighted the pathomechanistic importance of up-regulated genes comprised by the gene ontology terms “viral replication” and “humoral immune response” as well as down-regulated genes functionally related to “metabolite and energy

  6. Transcriptional changes in canine distemper virus-induced demyelinating leukoencephalitis favor a biphasic mode of demyelination.

    PubMed

    Ulrich, Reiner; Puff, Christina; Wewetzer, Konstantin; Kalkuhl, Arno; Deschl, Ulrich; Baumgärtner, Wolfgang

    2014-01-01

    Canine distemper virus (CDV)-induced demyelinating leukoencephalitis in dogs (Canis familiaris) is suggested to represent a naturally occurring translational model for subacute sclerosing panencephalitis and multiple sclerosis in humans. The aim of this study was a hypothesis-free microarray analysis of the transcriptional changes within cerebellar specimens of five cases of acute, six cases of subacute demyelinating, and three cases of chronic demyelinating and inflammatory CDV leukoencephalitis as compared to twelve non-infected control dogs. Frozen cerebellar specimens were used for analysis of histopathological changes including demyelination, transcriptional changes employing microarrays, and presence of CDV nucleoprotein RNA and protein using microarrays, RT-qPCR and immunohistochemistry. Microarray analysis revealed 780 differentially expressed probe sets. The dominating change was an up-regulation of genes related to the innate and the humoral immune response, and less distinct the cytotoxic T-cell-mediated immune response in all subtypes of CDV leukoencephalitis as compared to controls. Multiple myelin genes including myelin basic protein and proteolipid protein displayed a selective down-regulation in subacute CDV leukoencephalitis, suggestive of an oligodendrocyte dystrophy. In contrast, a marked up-regulation of multiple immunoglobulin-like expressed sequence tags and the delta polypeptide of the CD3 antigen was observed in chronic CDV leukoencephalitis, in agreement with the hypothesis of an immune-mediated demyelination in the late inflammatory phase of the disease. Analysis of pathways intimately linked to demyelination as determined by morphometry employing correlation-based Gene Set Enrichment Analysis highlighted the pathomechanistic importance of up-regulated genes comprised by the gene ontology terms "viral replication" and "humoral immune response" as well as down-regulated genes functionally related to "metabolite and energy generation".

  7. Pathogenesis and molecular biology of progressive multifocal leukoencephalopathy, the JC virus-induced demyelinating disease of the human brain.

    PubMed Central

    Major, E O; Amemiya, K; Tornatore, C S; Houff, S A; Berger, J R

    1992-01-01

    disease, for which no consensus of antiviral therapy exists, may yield to innovative treatment protocols. Images PMID:1310438

  8. Evaluation of a patient with suspected chronic demyelinating polyneuropathy.

    PubMed

    Jani-Acsadi, Agnes; Lewis, Richard A

    2013-01-01

    Demyelinating neuropathies are typically characterized by physiological slowing of conduction velocity and pathologically by segmental loss of myelin and in some instances, evidence of remyelination. Clinically, patients with demyelinating neuropathy can be seen with inherited disorders (Charcot-Marie-Tooth disease) or acquired disorders, typically immune-mediated or inflammatory. The acquired disorders can be either acute or subacute as seen in the acute inflammatory demyelinating polyneuropathy (AIDP) form of Guillain-Barré syndrome or chronic progressive or relapsing disorders such as chronic inflammatory demyelinating polyneuropathy. It is important to develop a logical approach to diagnosing these disorders. This requires an understanding of the clinical, genetic, physiological, and pathological features of these neuropathies. Clinically, important features to consider are the temporal progression, degree of symmetry, and involvement of proximal as well as distal muscles. Genetically, recognizing the different inheritance patterns and age of onset allow for a coordinated approach to determining a specific genotype. Physiologically, besides nerve conduction slowing, other physiological hallmarks of demyelination include temporal dispersion of compound motor action potentials (CMAP) on proximal stimulation, conduction block, and distal CMAP duration prolongation with certain patterns of involvement pointing to specific disorders. This chapter focuses on these various aspects of the evaluation of patients with chronic acquired demyelinating neuropathies to develop a comprehensive and thoughtful diagnostic concept.

  9. Challenges in pediatric chronic inflammatory demyelinating polyneuropathy.

    PubMed

    Haliloğlu, Göknur; Yüksel, Deniz; Temoçin, Cağri Mesut; Topaloğlu, Haluk

    2016-12-01

    Chronic inflammatory demyelinating neuropathy, a treatable immune-mediated disease of the peripheral nervous system is less common in childhood compared to adults. Despite different sets of diagnostic criteria, lack of a reliable biologic marker leads to challenges in diagnosis, follow-up and treatment. Our first aim was to review clinical presentation, course, response to treatment, and prognosis in our childhood patients. We also aimed to document diagnostic and therapeutic pitfalls and challenges at the bedside. Our original cohort consisted of 23 pediatric patients who were referred to us with a clinical diagnosis of chronic inflammatory demyelinating neuropathy. Seven patients reaching to an alternative diagnosis were excluded. In the remaining patients, diagnostic, treatment and follow-up data were compared in typical patients who satisfied both clinical and electrodiagnostic criteria and atypical patients who failed to meet minimal research chronic inflammatory demyelinating neuropathy electrodiagnostic requirements. Eight of 16 patients (50%) met the minimal chronic inflammatory demyelinating neuropathy research diagnostic requirements. There was only a statistically significant difference (p = 0.010) in terms of European Neuromuscular Centre childhood chronic inflammatory diagnostic mandatory clinical criteria between the two groups. Misdiagnosis due to errors in electrophysiological interpretation (100%, n = 8), cerebrospinal fluid cytoalbuminologic dissociation (100%, n = 4 and/or subjective improvement on any immunotherapy modality (80 ± 19.27%)) was frequent. Pediatric CIDP is challenging in terms of diagnostic and therapeutic pitfalls at the bedside. Diagnostic errors due to electrophysiological interpretation, cerebrospinal fluid cytoalbuminologic dissociation, and/or subjective improvement on immunotherapy should be considered.

  10. A case of chronic inflammatory demyelinating polyneuropathy presented with unilateral ptosis.

    PubMed

    Izadi, Sadegh; Karamimagham, Sina; Poursadeghfard, Maryam

    2014-01-01

    Chronic Inflammatory Demyelinating Polyneuropathy is an autoimmune disease with progressive and relapsing courses. The main clinical presentations are diffuse deep tendon hyporeflexia or areflexia and symmetric proximal-distal muscles weakness. Myasthenia gravis is also an immune mediated disease with fluctuating ocular and bulbar symptoms and sometimes weakness. Although both myasthenia gravis and chronic inflammatory demyelinating polyneuropathy are immune mediated disorders, clinical presentations are obviously different in the two diseases. Herein, we will report a case of chronic inflammatory demyelinating polyneuropathy who presented with isolated unilateral ptosis. Initially, the patient was managed as ocular type of myasthenia gravis, but after progression to general limb weakness and areflexia, the diagnosis of chronic inflammatory demyelinating polyneuropathy was made. Although unilateral ptosis is a typical feature of myasthenia gravis, it may be seen as the first presentation of chronic inflammatory demyelinating polyneuropathy as well which mimics myasthenia gravis disease.

  11. Distribution patterns of demyelination correlate with clinical profiles in chronic inflammatory demyelinating polyneuropathy

    PubMed Central

    Kuwabara, S; Ogawara, K; Misawa, S; Mori, M; Hattori, T

    2002-01-01

    Background: Chronic inflammatory demyelinating polyneuropathy (CIDP) is a heterogeneous disorder having a wide clinical range, and is characterised by multifocal demyelination that can involve the distal nerve terminals, intermediate nerve segments, and nerve roots. Objective: To investigate whether the distribution patterns of demyelination along the course of the nerve correlate with clinical profiles in patients with CIDP. Methods: Motor nerve conduction studies were carried out on 42 consecutive patients. According to the physiological criteria for demyelination, the presence of a demyelinative lesion was determined in the distal nerve segments (distal pattern) or intermediate nerve segments (intermediate pattern), or in both (diffuse pattern). The serum concentration of tumour necrosis factor (TNF)-α was measured by immunoassay. Results: Patients were classified as having a distal (n=10), intermediate (n=13), or diffuse (n=15) pattern, or were unclassified (n=4). Patients with the distal or diffuse pattern had common clinical features such as subacute onset, symmetric symptoms, and weakness involving proximal as well as distal muscles. Patients with the distal pattern had a good response to treatment and a monophasic remitting course, but the diffuse pattern was associated with a treatment dependent relapsing course, reflecting longer disease activity. The serum TNF-α concentrations increased only in the "diffuse" subgroup of patients, and this might be associated with breakdown of the blood-nerve barrier and therefore, involvement of the intermediate segments. The intermediate pattern was characterised by a chronic course, asymmetric symptoms, less severe disability, and refractoriness to treatments. Conclusions: CIDP consists of subtypes with varying predilections for lesions along the course of the nerve. The distribution patterns of conduction abnormalities may be useful in the prediction of outcome of patients with CIDP. PMID:11784822

  12. Carcinoma of Maxillary Sinus Masquerading as Odontogenic Infection

    PubMed Central

    Ramachamparambathu, Ashir Kolikkal; Vengal, Manoj; Siyo, Nizaro; Ahmed, Anis

    2016-01-01

    Malignant tumours of maxillary sinus are rare. They are usually diagnosed in the late stages when they perforate the sinus walls. The presence of large air space in the maxillary sinus facilitates asymptomatic growth of the sinus malignancy. The clinical presentation of these tumours depends on the sinus wall involved by the disease. The medial wall is usually the first to become eroded, leading to nasal obstruction, epistaxis or discharge. Rarely, symptoms of maxillary sinus carcinoma can resemble dental infection and the affected patients may visit dental clinic seeking treatment. This report presents a case of carcinoma of maxillary sinus mimicking odontogenic infection. Computed tomographic findings explained the reason for the present lesion to masquerade as an inflammatory condition. The importance of advanced imaging modalities for prompt identification of such lesions is discussed. PMID:27790593

  13. Pretibial Myxedema Masquerading as a Venous Leg Ulcer.

    PubMed

    Herskovitz, Ingrid; Hughes, Olivia; MacQuhae, Flor; Kirsner, Robert S

    2017-03-01

    The authors report a case of pretibial myxedema (PTM) masquerading as a venous leg ulcer to alert wound care clinicians to this diagnostic possibility. Pretibial myxedema is a localized form of mucin cutaneous deposition characterized by indurated plaques most commonly on anterior legs. It is more likely to present in patients with Graves' disease, but it can be found in euthyroid patients as well. The physiopathology of PTM is complex, and there is an accumulation of highly hydrophilic glycosaminoglycans in the dermis. Minimal morbidity is associated with PTM, but the pruritus related to mucin deposition can be intense. The skin around venous leg ulcers and the skin changes related to PTM can have a similar clinical presentation, which may be a reason PTM is under-recognized.

  14. Securing iris recognition systems against masquerade attacks

    NASA Astrophysics Data System (ADS)

    Galbally, Javier; Gomez-Barrero, Marta; Ross, Arun; Fierrez, Julian; Ortega-Garcia, Javier

    2013-05-01

    A novel two-stage protection scheme for automatic iris recognition systems against masquerade attacks carried out with synthetically reconstructed iris images is presented. The method uses different characteristics of real iris images to differentiate them from the synthetic ones, thereby addressing important security flaws detected in state-of-the-art commercial systems. Experiments are carried out on the publicly available Biosecure Database and demonstrate the efficacy of the proposed security enhancing approach.

  15. Chronic inflammatory demyelinating polyneuropathy.

    PubMed

    Mathey, Emily K; Pollard, John D

    2013-10-15

    Chronic inflammatory demyelinating polyneuropathy (CIDP) is the commonest treatable neuropathy in the western world. Untreated it may result in severe disability but if diagnosed and treated early there is effective treatment for the majority of patients. Typical CIDP is readily recognised but the diagnosis of other subgroups can be more challenging. The pathology of polyradiculoneuropathies such as CIDP characteristically affects the most proximal regions of the peripheral nervous system, nerve roots and major plexuses. It is important to test these regions with electrodiagnostic studies since routine neurophysiology may not encounter regions of pathology. Although accepted as an autoimmune disorder with an underlying immunopathology involving T cell and B cell responses, there is no agreement on major target antigens; however recent studies have highlighted a role for molecules in non compact myelin which play an essential role in the formation and maintenance of the nodal structures and hence in the function of ion channels central to saltatory conduction. Controlled trials have proven the efficacy of corticosteroid, intravenous immunoglobulin and plasma exchange in the short term and intravenous immunoglobulin also in the long term. Immunosuppressive agents are widely used but their efficacy has not been proven in controlled trials. Recent trials have shown the importance of attempting treatment withdrawal in patients apparently in remission to conserve treatments that are very expensive and in short supply, since a significant proportion of patients may enter long lasting remission following short term therapy. For the relatively small group of patients who do not respond to these first line therapies new agents including monoclonal antibodies may have a role.

  16. Masquerading bundle branch block: a variety of right bundle branch block with left anterior fascicular block.

    PubMed

    Elizari, Marcelo V; Baranchuk, Adrian; Chiale, Pablo A

    2013-01-01

    The so-called 'masquerading' type of right bundle branch block is caused by the simultaneous presence of a high-degree left anterior fascicular block often accompanied with severe left ventricular enlargement and/or fibrotic block in the anterolateral wall of the left ventricle. These conditions tend to reorient the terminal electrical forces of the QRS complex towards the left and upwards, in such a way that the characteristic slurred S wave in lead I becomes smaller or even disappears. In many cases of standard masquerading right bundle branch block, a small Q wave in lead I is present due to the initial forces of the left anterior fascicular block, which are oriented rightwards and inferiorly. However, in some cases, the Q wave in lead I also vanishes, and the mimicking of a left bundle branch block becomes perfect in standard leads. This is commonly associated with an inferior myocardial infarction or severe inferior fibrosis in cardiomyopathies. The typical QRS changes of right bundle branch block may eventually be concealed even in the right precordial leads; under such circumstances, the ECG diagnosis may be mistaken and the right bundle branch block totally missed. The masquerading right bundle branch block carries a poor prognosis, since it always implies the presence of a severe underlying heart disease.

  17. Multifocal Motor Neuropathy, Multifocal Acquired Demyelinating Sensory and Motor Neuropathy and Other Chronic Acquired Demyelinating Polyneuropathy Variants

    PubMed Central

    Barohn, Richard J.; Katz, Jonathan

    2014-01-01

    Chronic acquired demyelinating neuropathies (CADP) are an important group of immune neuromuscular disorders affecting myelin. These are distinct from chronic inflammatory demyelinating polyneuropathy (CIDP). Classically, CIDP is characterized by proximal and distal weakness, large fiber sensory loss, elevated cerebrospinal fluid (CSF) protein content, demyelinating changes nerve conduction studies or nerve biopsy, and response to immunomodulating treatment. In this chapter we discuss CADP with emphasis on multifocal motor neuropathy (MMN), multifocal acquired demyelinating sensory and motor neuropathy (MADSAM), distal acquired demyelinating symmetric (DADS) neuropathy and conclude with less common variants. While each of these entities has distinctive laboratory and electrodiagnostic features that aid in their diagnosis, clinical characteristics are of paramount importance in diagnosing specific conditions and determining the most appropriate therapies. Unlike CIDP, MMN is typically asymmetric and affects only the motor nerve fibers. MMN is a rare disease that presents chronically, over several years of progression affecting the arms are more commonly than the legs. Men are more likely than women to develop MMN. MADSAM should be suspected in patients who have weakness and loss of sensation in primarily one arm or leg which progresses slowly over several months to years. It is important in patient with multifocal demyelinating clinical presentation to distinguish MMN from MADSAM since corticosteroids are not effective in MMN where the mainstay of therapy is intravenous gammaglobulin (IVIg). DADS can be subdivided into DADS-M (associated woth M-protein) and DADS-I which is idioapthic. While DADS-I patients respond somewhat to immunotherapy, DADS-M patients present with distal predominant sensorimotor demyelinating neuropathy phenotype and are notoriously refractory to immunotherapies regardless of antibodies to myelin-associated glycoprotein (MAG). Our knowledge

  18. Childhood chronic inflammatory demyelinating polyneuropathy: an overview of 10 cases in the modern era.

    PubMed

    Ware, Tyson L; Kornberg, Andrew J; Rodriguez-Casero, M Victoria; Ryan, Monique M

    2014-01-01

    Chronic inflammatory demyelinating polyneuropathy is a rare condition in children. In this article, we report our experience in the management of 10 cases of childhood chronic inflammatory demyelinating polyneuropathy in a single center, in the era of contrast-enhanced magnetic resonance imaging (MRI), genetic microarray, and chronic inflammatory demyelinating polyneuropathy disease activity status. Robust neurophysiologic abnormalities were present in all cases and both MRI and lumbar puncture were useful adjuncts in diagnosis. Genetic microarray is a simple technique useful in excluding the most common hereditary demyelinating neuropathy. Intravenous immunoglobulin was an effective first-line therapy in most cases, with refractory cases responding to corticosteroids and rituximab. We found the chronic inflammatory demyelinating polyneuropathy disease activity status useful for assessing outcome at final follow-up, whereas the modified Rankin score was better for assessing peak motor disability.

  19. Quantifying Demyelination in NK venom treated nerve using its electric circuit model

    PubMed Central

    Das, H. K.; Das, D.; Doley, R.; Sahu, P. P.

    2016-01-01

    Reduction of myelin in peripheral nerve causes critical demyelinating diseases such as chronic inflammatory demyelinating polyneuropathy, Guillain-Barre syndrome, etc. Clinical monitoring of these diseases requires rapid and non-invasive quantification of demyelination. Here we have developed formulation of nerve conduction velocity (NCV) in terms of demyelination considering electric circuit model of a nerve having bundle of axons for its quantification from NCV measurements. This approach has been validated and demonstrated with toad nerve model treated with crude Naja kaouthia (NK) venom and also shows the effect of Phospholipase A2 and three finger neurotoxin from NK-venom on peripheral nerve. This opens future scope for non-invasive clinical measurement of demyelination. PMID:26932543

  20. Quantifying Demyelination in NK venom treated nerve using its electric circuit model

    NASA Astrophysics Data System (ADS)

    Das, H. K.; Das, D.; Doley, R.; Sahu, P. P.

    2016-03-01

    Reduction of myelin in peripheral nerve causes critical demyelinating diseases such as chronic inflammatory demyelinating polyneuropathy, Guillain-Barre syndrome, etc. Clinical monitoring of these diseases requires rapid and non-invasive quantification of demyelination. Here we have developed formulation of nerve conduction velocity (NCV) in terms of demyelination considering electric circuit model of a nerve having bundle of axons for its quantification from NCV measurements. This approach has been validated and demonstrated with toad nerve model treated with crude Naja kaouthia (NK) venom and also shows the effect of Phospholipase A2 and three finger neurotoxin from NK-venom on peripheral nerve. This opens future scope for non-invasive clinical measurement of demyelination.

  1. Quantifying Demyelination in NK venom treated nerve using its electric circuit model.

    PubMed

    Das, H K; Das, D; Doley, R; Sahu, P P

    2016-03-02

    Reduction of myelin in peripheral nerve causes critical demyelinating diseases such as chronic inflammatory demyelinating polyneuropathy, Guillain-Barre syndrome, etc. Clinical monitoring of these diseases requires rapid and non-invasive quantification of demyelination. Here we have developed formulation of nerve conduction velocity (NCV) in terms of demyelination considering electric circuit model of a nerve having bundle of axons for its quantification from NCV measurements. This approach has been validated and demonstrated with toad nerve model treated with crude Naja kaouthia (NK) venom and also shows the effect of Phospholipase A2 and three finger neurotoxin from NK-venom on peripheral nerve. This opens future scope for non-invasive clinical measurement of demyelination.

  2. Electrostimulation of the nervous system for patients with demyelinating and degenerative diseases of the nervous system and vascular diseases of the extremities.

    PubMed

    Dooley, D M; Sharkey, J

    The results of electrostimulation of the spinal cord for symptoms other than that of pain are recorded in this publication. 50% of patients with multiple sclerosis, primary lateral sclerosis and hereditary spino-cerebellar disorders were observed to have enduring favourable changes in neurological function during the 15 to 27 months they have been followed. The patients who were the least severely disabled had the greatest amount of increased function and were benefitted the most by the stimulation. Those who had the fewest neurological pathways affected make the most rapid progress. For example, the patient with only an ataxic or spastic gait was observed to improve faster than the patient with an ataxic and a spastic gait. The long-term effect of electrostimulation of the spinal cord on patients with these diseases is unknown at the present time. The purpose of the stimulation is to increase neurological function so that the patient can live a better life style. It is not thought that the electrical current is responsible for a 'cure' of the basic disease process. Electrostimulation of the posterior spinal roots and spinal cord, while not new, has not been used extensively for the treatment of patients with arterial disease. The patients who have responded the most dramatically to electrostimulation are those with vasospastic disorders. A larger percentage of patients showed a greater response to implanted stimulation than to transcutaneous stimulation. Electrostimulation of the nervous system is not designed to replace standard therapeutic measures of treatment of patients with vascular disease but to supplement them.

  3. Density-dependent predation influences the evolution and behavior of masquerading prey.

    PubMed

    Skelhorn, John; Rowland, Hannah M; Delf, Jon; Speed, Michael P; Ruxton, Graeme D

    2011-04-19

    Predation is a fundamental process in the interaction between species, and exerts strong selection pressure. Hence, anti-predatory traits have been intensively studied. Although it has long been speculated that individuals of some species gain protection from predators by sometimes almost-uncanny resemblances to uninteresting objects in the local environment (such as twigs or stones), demonstration of antipredatory benefits to such "masquerade" have only very recently been demonstrated, and the fundamental workings of this defensive strategy remain unclear. Here we use laboratory experiments with avian predators and twig-mimicking caterpillars as masqueraders to investigate (i) the evolutionary dynamics of masquerade; and (ii) the behavioral adaptations associated with masquerade. We show that the benefit of masquerade declines as the local density of masqueraders relative to their models (twigs, in our system) increases. This occurs through two separate mechanisms: increasing model density both decreased predators' motivation to search for masqueraders, and made masqueraders more difficult to detect. We further demonstrated that masquerading organisms have evolved complex microhabitat selection strategies that allow them to best exploit the density-dependent properties of masquerade. Our results strongly suggest the existence of opportunity costs associated with masquerade. Careful evaluation of such costs will be vital to the development of a fuller understanding of both the distribution of masquerade across taxa and ecosystems, and the evolution of the life history strategies of masquerading prey.

  4. Assessment of hindlimb gait as a powerful indicator of axonal loss in a murine model of progressive CNS demyelination

    PubMed Central

    McGavern, Dorian B.; Zoecklein, Laurie; Sathornsumetee, Sith; Rodriguez, Moses

    2017-01-01

    Identifying the role of axonal injury in the development of permanent, irreversible neurologic disability is important to the study of central nervous system (CNS) demyelinating diseases. Our understanding of neurologic dysfunction in demyelinating diseases and the ability to assess therapeutic interventions depends on the development of objective functional assays that can non-invasively measure axonal loss. In this study, we demonstrate in a murine model of progressive CNS demyelination that assessment of the hindlimb width of stride provides a powerful indicator of axonal loss and can dissociate between deficits induced by demyelination versus axonal loss. PMID:10986359

  5. Early identification of ‘acute-onset’ chronic inflammatory demyelinating polyneuropathy

    PubMed Central

    Sung, Jia-Ying; Tani, Jowy; Park, Susanna B.; Kiernan, Matthew C.

    2014-01-01

    Distinguishing patients with acute-onset chronic inflammatory demyelinating polyneuropathy from acute inflammatory demyelinating polyneuropathy prior to relapse is often challenging at the onset of their clinical presentation. In the present study, nerve excitability tests were used in conjunction with the clinical phenotype and disease staging, to differentiate between patients with acute-onset chronic inflammatory demyelinating polyneuropathy and patients with acute inflammatory demyelinating polyneuropathy at an early stage, with the aim to better guide treatment. Clinical assessment, staging and nerve excitability tests were undertaken on patients initially fulfilling the diagnostic criteria of acute inflammatory demyelinating polyneuropathy soon after symptom onset and their initial presentation. Patients were subsequently followed up for minimum of 12 months to determine if their clinical presentations were more consistent with acute-onset chronic inflammatory demyelinating polyneuropathy. Clinical severity as evaluated by Medical Research Council sum score and Hughes functional grading scale were not significantly different between the two cohorts. There was no difference between the time of onset of initial symptoms and nerve excitability test assessment between the two cohorts nor were there significant differences in conventional nerve conduction study parameters. However, nerve excitability test profiles obtained from patients with acute inflammatory demyelinating polyneuropathy demonstrated abnormalities in the recovery cycle of excitability, including significantly reduced superexcitability (P < 0.001) and prolonged relative refractory period (P < 0.01), without changes in threshold electrotonus. In contrast, in patients with acute-onset chronic inflammatory demyelinating polyneuropathy, a different pattern occurred with the recovery cycle shifted downward (increased superexcitability, P < 0.05; decreased subexcitability, P < 0.05) and increased

  6. [Demyelinating polyneuropathies in patients with diabetes mellitus and chronic alcoholic intoxication].

    PubMed

    Kovrazhkina, E A

    2012-01-01

    Frequency and nosological attribution of demyelinating polyneuropathies in patients with diabetes mellitus and alcoholism were determined. Eighty-six inpatients with alcoholic (n=46) and diabetic (n=40) polyneuropathy were examined clinically and using electroneuromyography (ENMG). A demyelinating pathogenetic variant was identified by clinical and ENMG data in 27 (31%) patients. Nine patients (33%) had dysimmune polyneuropathies (acute and chronic inflammatory demyelinating polyneuropathy). Polyneuropathies were specified as toxic/metabolic with the prevalence of a demyelinating component within the main disease in 18 (67%) patients. Clinical and ENMG-signs of the demyelinating variant of alcoholic and diabetic neuropathy are presented. The efficacy of the antioxidant berlition was shown for toxic/metabolic polyneuropathies while the addition of immune modulators was needed for treatment of dysimmune polyneuropathy.

  7. Disseminated Mycobacterium tuberculosis Infection Masquerading as Metastasis after Heavy Ion Radiotherapy for Prostate Cancer

    PubMed Central

    Ando, Masaru; Mukai, Yutaka; Ushijima, Ryo-ichi; Shioyama, Yoshiyuki; Umeki, Kenji; Okada, Fumito; Nureki, Shin-ichi; Mimata, Hiromitsu; Kadota, Jun-ichi

    2016-01-01

    Fluorodeoxyglucose (FDG)-positron emission tomography with computed tomography (FDG-PET/CT) is useful in disease monitoring of malignancies after therapy, while an FDG uptake may also be present in benign diseases. We herein demonstrate a case of disseminated Mycobacterium tuberculosis mimicking systemic metastasis of prostate cancer. This case highlights that clinicians should consider Mycobacterium tuberculosis in patients with prostate cancer who demonstrate multifocal FDG uptakes masquerading as metastasis, even when the chest photographs reveal a normal appearance and a sputum examination demonstrates negative results. An invasive surgical biopsy may be required and a pathological analysis would be critical in the diagnosis of Mycobacterium tuberculosis. PMID:27853089

  8. Influence of laser irradiation on demyelination of nervous fibers

    NASA Astrophysics Data System (ADS)

    Melnik, Nataly O.; Plaksij, Yu. S.; Mamilov, Serge A.

    2000-11-01

    Problem demyelinating diseases from actual in modern of neurology. Main disease of this group - multiple sclerosis, which morphological manifestation is the process demyelineation - disintegration of myelin, which covers axial cylinders of nervous filaments. The outcome of such damage is violation of realization of nervous impulses, dissonance of implement and coordination functions. Most typical the feature of a multiple sclerosis is origin of repeated remissions, which compact with indication remyelination. In development of disease the large role is played by modifications of immunological of a reactivity of an organism. The purpose of the title is development of new methods of treatment of a multiple sclerosis because of lasertherapy. For thsi purpose the influence of a laser exposure on demyelination and remyelination processes will be investigated, is investigated pathological fabrics at microscopic and submicroscopic levels. The study of proceses demyelination and remyelination will be conducted on experimental animals (rats), which are sick experimental allergic encephalomyelitis (EAE), that is the most adequate model of a multiple sclerosis. The patients' EAE animals will be subjected to treatment by a laser exposure. For want of it there will be determinate optimum lengths of waves, dozes and modes of laser radiation.

  9. Chronic dysimmune neuropathies: Beyond chronic demyelinating polyradiculoneuropathy

    PubMed Central

    Khadilkar, Satish V.; Deshmukh, Shrikant S.; Dhonde, Pramod D.

    2011-01-01

    The spectrum of chronic dysimmune neuropathies has widened well beyond chronic demyelinating polyradiculoneuropathy (CIDP). Pure motor (multifocal motor neuropathy), sensorimotor with asymmetrical involvement (multifocal acquired demylinating sensory and motor neuropathy), exclusively distal sensory (distal acquired demyelinating sensory neuropathy) and very proximal sensory (chronic immune sensory polyradiculopathy) constitute the variants of CIDP. Correct diagnosis of these entities is of importance in terms of initiation of appropriate therapy as well as prognostication of these patients. The rates of detection of immune-mediated neuropathies with monoclonal cell proliferation (monoclonal gammopathy of unknown significance, multiple myeloma, etc.) have been facilitated as better diagnostic tools such as serum immunofixation electrophoresis are being used more often. Immune neuropathies associated with malignancies and systemic vasculitic disorders are being defined further and treated early with better understanding of the disease processes. As this field of dysimmune neuropathies will evolve in the future, some of the curious aspects of the clinical presentations and response patterns to different immunosuppressants or immunomodulators will be further elucidated. This review also discusses representative case studies. PMID:21808468

  10. The Effect of Age on the Susceptibility and Severity of Demyelination

    DTIC Science & Technology

    2015-10-01

    EAE, aging, neurofascin, transgenics, demyelinating disease, multiple sclerosis . Accomplishments- The accomplishments on this project will be...results will impact our understanding of the consequences of multiple sclerosis in an aging population. In particular we have determined that in the

  11. Density-dependent predation influences the evolution and behavior of masquerading prey

    PubMed Central

    Skelhorn, John; Rowland, Hannah M.; Delf, Jon; Speed, Michael P.; Ruxton, Graeme D.

    2011-01-01

    Predation is a fundamental process in the interaction between species, and exerts strong selection pressure. Hence, anti-predatory traits have been intensively studied. Although it has long been speculated that individuals of some species gain protection from predators by sometimes almost-uncanny resemblances to uninteresting objects in the local environment (such as twigs or stones), demonstration of antipredatory benefits to such “masquerade” have only very recently been demonstrated, and the fundamental workings of this defensive strategy remain unclear. Here we use laboratory experiments with avian predators and twig-mimicking caterpillars as masqueraders to investigate (i) the evolutionary dynamics of masquerade; and (ii) the behavioral adaptations associated with masquerade. We show that the benefit of masquerade declines as the local density of masqueraders relative to their models (twigs, in our system) increases. This occurs through two separate mechanisms: increasing model density both decreased predators’ motivation to search for masqueraders, and made masqueraders more difficult to detect. We further demonstrated that masquerading organisms have evolved complex microhabitat selection strategies that allow them to best exploit the density-dependent properties of masquerade. Our results strongly suggest the existence of opportunity costs associated with masquerade. Careful evaluation of such costs will be vital to the development of a fuller understanding of both the distribution of masquerade across taxa and ecosystems, and the evolution of the life history strategies of masquerading prey. PMID:21464318

  12. Cardiac sarcoid: a chameleon masquerading as hypertrophic cardiomyopathy and dilated cardiomyopathy in the same patient.

    PubMed

    Agarwal, Anushree; Sulemanjee, Nasir Z; Cheema, Omar; Downey, Francis X; Tajik, A Jamil

    2014-05-01

    Sarcoidosis is a multisystem, granulomatous disease of unknown etiology often seen in young adults, with cardiac involvement in more than one-quarter of sarcoid patients. The clinical presentation of cardiac sarcoid depends upon the location and extent of myocardium involved. Although cardiac sarcoid may produce asymmetrical septal hypertrophy, it is most commonly considered in the differential diagnosis of dilated cardiomyopathy. The hypertrophic stage of cardiac sarcoid is rarely seen. We describe a case of cardiac sarcoid in a young patient wherein a distinctive appearance of the cardiac sarcoid spectrum from "hypertrophic" stage to thinned/scarred stage, masquerading as hypertrophic cardiomyopathy followed by dilated cardiomyopathy, is demonstrated.

  13. Demyelination precedes oligodendrocyte loss in canine distemper virus-induced encephalitis.

    PubMed

    Schobesberger, M; Zurbriggen, A; Doherr, M G; Weissenböck, H; Vandevelde, M; Lassmann, H; Griot, C

    2002-01-01

    Canine distemper virus (CDV), a negative-stranded RNA morbillivirus, causes a persistent infection within the central nervous system resulting in a progressive, multifocal demyelinating disease. Demyelination is thought to be caused by a selective alteration of the myelin-producing oligodendrocytes. Metabolic impairment and morphological changes of the oligodendrocytes after CDV infection have previously been observed in vitro as well as in vivo. Until now it has been suggested that the oligodendrocytes completely disappear from CDV-induced demyelinating lesions. However, ultrastructural analysis in brain tissue sections and immunohistochemical examination of oligodendrocytes in dog brain cell cultures contradicted these observations. In this study oligodendrocytes from different categories of CDV-induced lesions were examined by in situ hybridization for proteolipid protein mRNA and--as a new tool employed on canine brain tissue sections--by immunohistochemistry using a monoclonal antibody against 2',3'-cyclic nucleotide 3'-phosphodiesterase, a myelin-specific enzyme. A down-regulation in the myelin gene transcription was detected already before demyelination occurred. However, a decrease in the number of oligodendrocytes was not observed until demyelination became evident. Although there was further depletion of oligodendrocytes in plaques with progressive demyelination, we demonstrated for the first time that these cells were still present in a significant amount even in chronic, completely demyelinated distemper lesions.

  14. Cuprizone-induced demyelination in mice: age-related vulnerability and exploratory behavior deficit.

    PubMed

    Wang, Hongkai; Li, Chengren; Wang, Hanzhi; Mei, Feng; Liu, Zhi; Shen, Hai-Ying; Xiao, Lan

    2013-04-01

    Schizophrenia is a mental disease that mainly affects young individuals (15 to 35 years old) but its etiology remains largely undefined. Recently, accumulating evidence indicated that demyelination and/or dysfunction of oligodendrocytes is an important feature of its pathogenesis. We hypothesized that the vulnerability of young individuals to demyelination may contribute to the onset of schizophrenia. In the present study, three different age cohorts of mice, i.e. juvenile (3 weeks), young-adult (6 weeks) and middle-aged (8 months), were subjected to a 6-week diet containing 0.2% cuprizone (CPZ) to create an animal model of acute demyelination. Then, age-related vulnerability to CPZ-induced demyelination, behavioral outcomes, and myelination-related molecular biological changes were assessed. We demonstrated: (1) CPZ treatment led to more severe demyelination in juvenile and young-adult mice than in middle-aged mice in the corpus callosum, a region closely associated with the pathophysiology of schizophrenia; (2) the higher levels of demyelination in juvenile and young-adult mice were correlated with a greater reduction of myelin basic protein, more loss of CC-1-positive mature oligodendrocytes, and higher levels of astrocyte activation; and (3) CPZ treatment resulted in a more prominent exploratory behavior deficit in juvenile and young-adult mice than in middle-aged mice. Together, our data demonstrate an age-related vulnerability to demyelination with a concurrent behavioral deficit, providing supporting evidence for better understanding the susceptibility of the young to the onset of schizophrenia.

  15. Rathke cleft cyst masquerading as pituitary abscess

    PubMed Central

    Yang, Chengxian; Bao, Xinjie; Liu, Xiaohai; Deng, Kan; Feng, Ming; Yao, Yong; Wang, Renzhi

    2017-01-01

    Abstract Background: Rathke cleft cyst (RCC) is a rare cystic sellar entity, which is usually small in size and asymptomatic in most patients. RCC presenting panhypopituitarism and a cystic lesion with rim enhancement on magnetic resonance imaging is extremely rare. Therefore, it is easy to be misdiagnosed as pituitary abscess because of the similar clinical manifestations and neuroimaging changes. Case summary: We report a rare case of RCC masquerading as pituitary abscess clinically and radiologically with no evidence of central nervous system infection. The patient was initially suspected to be diagnosed with pituitary abscess, which was denied by the histopathological findings of RCC with no intraoperative drainage of abscess. We present an uncommon case of RCC masquerading as pituitary abscess in a 62-year-old Chinese male patient. The patient was admitted to Peking Union Medical College Hospital complaining of severe frontal pulsatile headache, visual acuity deficit, polyuria, polydipsia, and slight disturbance of consciousness. The biochemical and endocrinological examinations revealed severe hyponatremia and panhypopituitarism. Magnetic resonance imaging showed a sellar lesion with the apparent cystic change and rim enhancement. Accordingly, pituitary abscess was misdiagnosed at the beginning. The patient received hormone replacement therapy and underwent a trans-sphenoidal surgery. The surgical findings were uneventful. The histopathological examinations showed no infiltration of inflammatory cells or pus, and proved the lesion to be RCC. Conclusion: Through this rare case, we aim to emphasize that the differential diagnosis of sellar lesions requires constant vigilance and that RCC may lead to clinical and radiological changes similar with pituitary abscess. PMID:28272259

  16. Is distal motor and/or sensory demyelination a distinctive feature of anti-MAG neuropathy?

    PubMed

    Lozeron, Pierre; Ribrag, Vincent; Adams, David; Brisset, Marion; Vignon, Marguerite; Baron, Marine; Malphettes, Marion; Theaudin, Marie; Arnulf, Bertrand; Kubis, Nathalie

    2016-09-01

    To report the frequency of the different patterns of sensory and motor electrophysiological demyelination distribution in patients with anti-MAG neuropathy in comparison with patients with IgM neuropathy without MAG reactivity (IgM-NP). Thirty-five anti-MAG patients at early disease stage (20.1 months) were compared to 23 patients with IgM-NP; 21 CIDP patients and 13 patients with CMT1a neuropathy were used as gold standard neuropathies with multifocal and homogeneous demyelination, respectively. In all groups, standard motor and sensory electrophysiological parameters, terminal latency index and modified F ratio were investigated. Motor electrophysiological demyelination was divided in four profiles: distal, homogeneous, proximal, and proximo-distal. Distal sensory and sensorimotor demyelination were evaluated. Anti-MAG neuropathy is a demyelinating neuropathy in 91 % of cases. In the upper limbs, reduced TLI is more frequent in anti-MAG neuropathy, compared to IgM-NP. But, predominant distal demyelination of the median nerve is encountered in only 43 % of anti-MAG neuropathy and is also common in IgM-NP (35 %). Homogeneous demyelination was the second most frequent pattern (31 %). Concordance of electrophysiological profiles across motor nerves trunks is low and median nerve is the main site of distal motor conduction slowing. Reduced sensory conduction velocities occurs in 14 % of patients without evidence of predominant distal slowing. Simultaneous sensory and motor distal slowing was more common in the median nerve of anti-MAG neuropathy than IgM-NP. Electrophysiological distal motor demyelination and sensory demyelination are not a distinctive feature of anti-MAG reactivity. In anti-MAG neuropathy it is mainly found in the median nerve suggesting a frequent nerve compression at wrist.

  17. Disinhibition of Cathepsin C Caused by Cystatin F Deficiency Aggravates the Demyelination in a Cuprizone Model

    PubMed Central

    Liang, Junjie; Li, Ning; Zhang, Yanli; Hou, Changyi; Yang, Xiaohan; Shimizu, Takahiro; Wang, Xiaoyu; Ikenaka, Kazuhiro; Fan, Kai; Ma, Jianmei

    2016-01-01

    Although the precise mechanism underlying initial lesion development in multiple sclerosis (MS) remains unclear, CNS inflammation has long been associated with demyelination, and axonal degeneration. The activation of microglia/macrophages, which serve as innate immune cells in the CNS, is the first reaction to even minor pathologic changes in the CNS and is considered an initial pathogenic event in MS. Microglial activation accompanies a variety of gene expressions, including cystatin F (Cys F), which belongs to the cystatin superfamily and is one of the cathepsin inhibitors. In our previous study we showed that Cys F has a unique expression pattern in microglia/macrophages in the demyelination process. Specifically, the timing of Cys F induction correlated with ongoing demyelination, and the sites of Cys F expression overlapped with areas of remyelination. Cys F induction ceased in chronic demyelination when remyelination capacity was lost, suggesting that Cys F expressed by microglia/macrophages may play an important role in demyelination and/or remyelination. The functional role of Cys F in demyelinating disease of the CNS, however, is unclear. Cys F gene knockout mice were used in the current study to clarify the functional role of Cys F in the demyelination process in a cuprizone-induced demyelination animal model. We demonstrated that absence of the Cys F gene and the resulting disinhibition of cathepsin C (Cat C) aggravates the demyelination, and this finding may be related to the increased expression of the glia-derived chemokine, CXCL2, which may attract inflammatory cells to sites of myelin sheath damage. This effect was reversed by knock down of the Cat C gene. The findings gain further insight to function of Cat C in pathophysiology of MS, which may have implications for therapeutics for the prevention of neuroinflammation-involved neurological disorders in the future. PMID:28066178

  18. Disinhibition of Cathepsin C Caused by Cystatin F Deficiency Aggravates the Demyelination in a Cuprizone Model.

    PubMed

    Liang, Junjie; Li, Ning; Zhang, Yanli; Hou, Changyi; Yang, Xiaohan; Shimizu, Takahiro; Wang, Xiaoyu; Ikenaka, Kazuhiro; Fan, Kai; Ma, Jianmei

    2016-01-01

    Although the precise mechanism underlying initial lesion development in multiple sclerosis (MS) remains unclear, CNS inflammation has long been associated with demyelination, and axonal degeneration. The activation of microglia/macrophages, which serve as innate immune cells in the CNS, is the first reaction to even minor pathologic changes in the CNS and is considered an initial pathogenic event in MS. Microglial activation accompanies a variety of gene expressions, including cystatin F (Cys F), which belongs to the cystatin superfamily and is one of the cathepsin inhibitors. In our previous study we showed that Cys F has a unique expression pattern in microglia/macrophages in the demyelination process. Specifically, the timing of Cys F induction correlated with ongoing demyelination, and the sites of Cys F expression overlapped with areas of remyelination. Cys F induction ceased in chronic demyelination when remyelination capacity was lost, suggesting that Cys F expressed by microglia/macrophages may play an important role in demyelination and/or remyelination. The functional role of Cys F in demyelinating disease of the CNS, however, is unclear. Cys F gene knockout mice were used in the current study to clarify the functional role of Cys F in the demyelination process in a cuprizone-induced demyelination animal model. We demonstrated that absence of the Cys F gene and the resulting disinhibition of cathepsin C (Cat C) aggravates the demyelination, and this finding may be related to the increased expression of the glia-derived chemokine, CXCL2, which may attract inflammatory cells to sites of myelin sheath damage. This effect was reversed by knock down of the Cat C gene. The findings gain further insight to function of Cat C in pathophysiology of MS, which may have implications for therapeutics for the prevention of neuroinflammation-involved neurological disorders in the future.

  19. Remodelling of motor nerve terminals in demyelinating axons of periaxin null mutant mice

    PubMed Central

    Court, Felipe A; Brophy, Peter J; Ribchester, Richard R

    2015-01-01

    Myelin formation around axons increases nerve conduction velocity and regulates phenotypic characteristics of the myelinated axon. In the peripheral nervous system, demyelinating forms of hereditary Charcot-Marie-Tooth (CMT) diseases, due to Schwann-cell intrinsic molecular defects, leads to reduced nerve conduction velocity and changes in the axonal phenotype. Several mouse models of CMT diseases have been generated, allowing the study of consequences of demyelination in peripheral nerve fibres. Nevertheless, the effect of demyelination at the level of the neuromuscular synapse has been largely overlooked. Here we show that in the periaxin knock-out mice, a model of CMT condition, neuromuscular junctions develop profound morphological changes in pre-terminal region of motoraxons. These changes include extensive preterminal branches which originate in demyelinated regions of the nerve fibre and axonal swellings associated with residually-myelinated regions of the fibre. Using intracellular recording from muscle fibres we detected asynchronous failure of action potential transmission at high but not low stimulation frequencies, a phenomenon consistent with branch point failure. Taken together, our morphological and electrophysiological findings suggest that preterminal branching due to segmental demyelination near the neuromuscular synapse in periaxin KO mice may underlie phenotypic disabilities present in this mouse model of CMT disease. These results opens a new avenue of research in order to understand the cellular changes responsible for clinical disabilities in demyelinating conditions. PMID:18205176

  20. Absence of neurological deficits following extensive demyelination in a class I-deficient murine model of multiple sclerosis

    PubMed Central

    Schmelzer, James D.; Hunter, Samuel F.; Low, Phillip A.; Rodriguez, Moses

    2017-01-01

    Demyelination alone has been considered sufficient for development of neurological deficits following central nervous system (CNS) disease. However, extensive demyelination is not always associated with clinical deficits in patients with multiple sclerosis (MS), the most common primary demyelinating disease in humans. We used the Theiler’s murine encephalomyelitis virus model of demyelination to investigate the role of major histocompatibility complex (MHC) class I and class II gene products in the development of functional and neurophysiological deficits following demyelination. We measured spontaneous clinical activity by two independent assays and recorded hind-limb motor-evoked potentials in infected class I-deficient and class II-deficient mice of an identical genetic background as well as in highly susceptible SJL/J mice. The results show that despite a similar distribution and extent of demyelinated lesions in all mice, only class I-deficient mice were functionally normal. We propose that the mechanism by which demyelinated class I-deficient mice maintain neurologic function results from increased sodium channel densities and the relative preservation of axons. These findings are the first to implicate a role for MHC class I in the development of neurological deficits following demyelination. PMID:9461192

  1. Brain microbiota disruption within inflammatory demyelinating lesions in multiple sclerosis

    PubMed Central

    Branton, W. G.; Lu, J. Q.; Surette, M. G.; Holt, R. A.; Lind, J.; Laman, J. D.; Power, C.

    2016-01-01

    Microbial communities reside in healthy tissues but are often disrupted during disease. Bacterial genomes and proteins are detected in brains from humans, nonhuman primates, rodents and other species in the absence of neurological disease. We investigated the composition and abundance of microbiota in frozen and fixed autopsied brain samples from patients with multiple sclerosis (MS) and age- and sex-matched nonMS patients as controls, using neuropathological, molecular and bioinformatics tools. 16s rRNA sequencing revealed Proteobacteria to be the dominant phylum with restricted diversity in cerebral white matter (WM) from MS compared to nonMS patients. Both clinical groups displayed 1,200–1,400 bacterial genomes/cm3 and low bacterial rRNA:rDNA ratios in WM. RNAseq analyses showed a predominance of Proteobacteria in progressive MS patients’ WM, associated with increased inflammatory gene expression, relative to a broader range of bacterial phyla in relapsing-remitting MS patients’ WM. Although bacterial peptidoglycan (PGN) and RNA polymerase beta subunit immunoreactivities were observed in all patients, PGN immunodetection was correlated with demyelination and neuroinflammation in MS brains. Principal component analysis revealed that demyelination, PGN and inflammatory gene expression accounted for 86% of the observed variance. Thus, inflammatory demyelination is linked to an organ-specific dysbiosis in MS that could contribute to underlying disease mechanisms. PMID:27892518

  2. Central Nervous System Demyelination and Remyelination is Independent from Systemic Cholesterol Level in Theiler's Murine Encephalomyelitis.

    PubMed

    Raddatz, Barbara B; Sun, Wenhui; Brogden, Graham; Sun, Yanyong; Kammeyer, Patricia; Kalkuhl, Arno; Colbatzky, Florian; Deschl, Ulrich; Naim, Hassan Y; Baumgärtner, Wolfgang; Ulrich, Reiner

    2016-01-01

    High dietary fat and/or cholesterol intake is a risk factor for multiple diseases and has been debated for multiple sclerosis. However, cholesterol biosynthesis is a key pathway during myelination and disturbances are described in demyelinating diseases. To address the possible interaction of dyslipidemia and demyelination, cholesterol biosynthesis gene expression, composition of the body's major lipid repositories and Paigen diet-induced, systemic hypercholesterolemia were examined in Theiler's murine encephalomyelitis (TME) using histology, immunohistochemistry, serum clinical chemistry, microarrays and high-performance thin layer chromatography. TME-virus (TMEV)-infected mice showed progressive loss of motor performance and demyelinating leukomyelitis. Gene expression associated with cholesterol biosynthesis was overall down-regulated in the spinal cord of TMEV-infected animals. Spinal cord levels of galactocerebroside and sphingomyelin were reduced on day 196 post TMEV infection. Paigen diet induced serum hypercholesterolemia and hepatic lipidosis. However, high dietary fat and cholesterol intake led to no significant differences in clinical course, inflammatory response, astrocytosis, and the amount of demyelination and remyelination in the spinal cord of TMEV-infected animals. The results suggest that down-regulation of cholesterol biosynthesis is a transcriptional marker for demyelination, quantitative loss of myelin-specific lipids, but not cholesterol occurs late in chronic demyelination, and serum hypercholesterolemia exhibited no significant effect on TMEV infection.

  3. Imaging and clinical properties of inflammatory demyelinating pseudotumor in the spinal cord

    PubMed Central

    Wang, Ying; Wang, Min; Liang, Hui; Yu, Quntao; Yan, Zhihui; Kong, Min

    2013-01-01

    Inflammatory demyelinating pseudotumor usually occurs in the brain and rarely occurs in the spinal cord. On imaging, inflammatory demyelinating pseudotumor appears very similar to intramedullary tumors such as gliomas. It is often misdiagnosed as intramedullary tumor and surgically resected. In view of this, the clinical and magnetic resonance imaging manifestations and the pathological fea-tures of 36 cases of inflammatory demyelinating pseudotumor in the spinal cord were retrospec-tively analyzed and summarized. Most of these cases suffered from acute or subacute onset and exhibited a sensorimotor disorder. Among them, six cases were misdiagnosed as having intra-dullary gliomas, and inflammatory demyelinating pseudotumor was only identified and pathologi-cally confirmed after surgical resection. Lesions in the cervical and thoracic spinal cord were com-mon. Magnetic resonance imaging revealed edema and space-occupying lesions to varying grees at the cervical-thoracic junction, with a predominant feature of non-closed rosette-like forcement (open-loop sign). Pathological examination showed perivascular cuffing of predominantly dense lymphocytes, and demyelination was observed in six of the misdiagnosed cases. These re-sults suggest that tumor-like inflammatory demyelinating disease in the spinal cord is a kind of special demyelinating disease that can be categorized as inflammatory pseudotumor. These solitary lesions are easily confused with intramedullary neoplasms. Patchy or non-closed reinforcement (open-ring sign) on magnetic resonance imaging is the predominant property of inflammatory myelinating pseudotumor, and inflammatory cell infiltration and demyelination are additional pa-logical properties. PMID:25206559

  4. Bronchioloalveolar carcinoma masquerading as pneumonia.

    PubMed

    Thompson, William H

    2004-11-01

    Bronchioloalveolar carcinoma (BAC) is a relatively rare adenocarcinoma that typically arises in the lung periphery and grows along alveolar walls, without destroying the lung parenchyma. It is often multicentric and may arise from a previously stable scar. Because the parenchyma is preserved and because BAC may arise simultaneously in multiple lobes, the chest radiograph and symptoms (cough, chest pain, and sputum production) may be indistinguishable from pneumonia or other noninfectious inflammatory processes (eg, hypersensitivity pneumonitis or bronchiolitis obliterans). The clinician should suspect BAC if what otherwise appears to be pneumonia lacks fever or leukocytosis or does not respond to antibiotics. BAC accounts for 2.6-4.3 % of all lung cancers. On a radiograph, BAC often appears as a solitary nodule, but may also appear as a patchy, lobar or multilobar infiltrates, often with air bronchograms indistinguishable from pneumonia. Positron-emission tomography does not help distinguish BAC from pneumonia. Among BAC patients, 62% present without symptoms and with only an abnormal radiograph, whereas 38% present with symptoms of cough, chest pain, and sputum production. Bronchoscopy is usually normal. Preoperative diagnosis with transbronchial biopsy, bronchoscopic cytology examination, or expectorated sputum cytology is more common with the diffuse or multicentric forms. Cure depends on complete resection. A trial of antibiotics and reassessment of clinical findings is a reasonable approach, but biopsy or cytology is the only means of ruling in malignancy and ruling out other etiologies, so biopsy should always be considered when a presumed pneumonia does not respond to antibiotics. I saw a 61-year-old man whose initial diagnosis was pneumonia. He took a 10-day course of oral azithromycin, but his symptoms and chest radiograph were unchanged. A tomogram showed interstitial prominence and peripheral air-space disease in the right upper and lower lobes

  5. Diagnoses in Pediatric Patients With Magnetic Resonance Imaging (MRI) Lesions Suspicious for Demyelination.

    PubMed

    Sweeney, Michael L; Kukreja, Marcia; Horn, Paul S; Standridge, Shannon M

    2015-10-01

    Magnetic resonance imaging (MRI) studies of the brain in pediatric patients frequently show abnormal white matter lesions, which may be concerning for demyelinating disease. This study aimed to determine the proportion of pediatric patients who have MRI lesions concerning for demyelinating disease at presentation and ultimately are diagnosed with a primary central nervous system demyelinating disease. A retrospective chart review was performed on MRI reports of patients who underwent imaging evaluation at a single tertiary pediatric hospital. Of 299 patients identified, 192 presented with acute neurologic complaints. In this group, ≥ 5 discrete lesions, African American race, and having brain stem, thalamic, cerebellar, or optic nerve lesions was associated with the patient being diagnosed with a disease that required further treatment. The other 107 patients underwent MRI for other indications. Among these subjects, having lesions within the corpus callosum or cerebellum was associated with being diagnosed with a disease requiring further treatment.

  6. Differential diagnosis and evaluation in pediatric inflammatory demyelinating disorders.

    PubMed

    Rostasy, Kevin; Bajer-Kornek, Barbara; Venkateswaran, Sunita; Hemingway, Cheryl; Tardieu, Marc

    2016-08-30

    Major advances have been made in the clinical and radiologic characterization of children presenting with the different forms of an acquired inflammatory demyelinating syndrome (ADS) such as acute disseminating encephalomyelitis, neuromyelitis optica spectrum disorders, and clinically isolated syndromes. Nevertheless, a proportion of cases that present with similar symptoms are due to a broad spectrum of other inflammatory disorders affecting the white matter, primary CNS tumors, or neurometabolic diseases. The clinician therefore has to be aware of the different forms of ADS, the risk factors for a chronic-relapsing course, and features that indicate an alternative diagnosis. The goal of this article is therefore to provide an outline of a pathway for evaluating pediatric patients with a presumed inflammatory demyelinating disorder and discussing the spectrum of the more common differential diagnoses.

  7. Gene expression changes in chronic inflammatory demyelinating polyneuropathy skin biopsies.

    PubMed

    Puttini, Stefania; Panaite, Petrica-Adrian; Mermod, Nicolas; Renaud, Susanne; Steck, Andreas J; Kuntzer, Thierry

    2014-05-15

    Chronic-inflammatory demyelinating polyneuropathy (CIDP) is an immune-mediated disease with no known biomarkers for diagnosing the disease or assessing its prognosis. We performed transcriptional profiling microarray analysis on skin punch biopsies from 20 CIDP patients and 17 healthy controls to identify disease-associated gene expression changes. We demonstrate changes in expression of genes involved in immune and chemokine regulation, growth and repair. We also found a combination of two upregulated genes that can be proposed as a novel biomarker of the disorder.

  8. When DLB, PD, and PSP masquerade as MSA

    PubMed Central

    Koga, Shunsuke; Aoki, Naoya; Uitti, Ryan J.; van Gerpen, Jay A.; Cheshire, William P.; Josephs, Keith A.; Wszolek, Zbigniew K.; Langston, J. William

    2015-01-01

    Objective: To determine ways to improve diagnostic accuracy of multiple system atrophy (MSA), we assessed the diagnostic process in patients who came to autopsy with antemortem diagnosis of MSA by comparing clinical and pathologic features between those who proved to have MSA and those who did not. We focus on likely explanations for misdiagnosis. Methods: This is a retrospective review of 134 consecutive patients with an antemortem clinical diagnosis of MSA who came to autopsy with neuropathologic evaluation of the brain. Of the 134 patients, 125 had adequate medical records for review. Clinical and pathologic features were compared between patients with autopsy-confirmed MSA and those with other pathologic diagnoses, including dementia with Lewy bodies (DLB), Parkinson disease (PD), and progressive supranuclear palsy (PSP). Results: Of the 134 patients with clinically diagnosed MSA, 83 (62%) had the correct diagnosis at autopsy. Pathologically confirmed DLB was the most common misdiagnosis, followed by PSP and PD. Despite meeting pathologic criteria for intermediate to high likelihood of DLB, several patients with DLB did not have dementia and none had significant Alzheimer-type pathology. Autonomic failure was the leading cause of misdiagnosis in DLB and PD, and cerebellar ataxia was the leading cause of misdiagnosis in PSP. Conclusions: The diagnostic accuracy for MSA was suboptimal in this autopsy study. Pathologically confirmed DLB, PD, and PSP were the most common diseases to masquerade as MSA. This has significant implications not only for patient care, but also for research studies in MSA cases that do not have pathologic confirmation. PMID:26138942

  9. Machine learning approach identifies new pathways associated with demyelination in a viral model of multiple sclerosis.

    PubMed

    Ulrich, Reiner; Kalkuhl, Arno; Deschl, Ulrich; Baumgärtner, Wolfgang

    2010-01-01

    Theiler's murine encephalomyelitis is an experimentally virus-induced inflammatory demyelinating disease of the spinal cord, displaying clinical and pathological similarities to chronic progressive multiple sclerosis. The aim of this study was to identify pathways associated with chronic demyelination using an assumption-free combined microarray and immunohistology approach. Movement control as determined by rotarod assay significantly worsened in Theiler's murine encephalomyelitis -virus-infected SJL/J mice from 42 to 196 days after infection (dpi). In the spinal cords, inflammatory changes were detected 14 to 196 dpi, and demyelination progressively increased from 42 to 196 dpi. Microarray analysis revealed 1001 differentially expressed genes over the study period. The dominating changes as revealed by k-means and functional annotation clustering included up-regulations related to intrathecal antibody production and antigen processing and presentation via major histocompatibility class II molecules. A random forest machine learning algorithm revealed that down-regulated lipid and cholesterol biosynthesis, differentially expressed neurite morphogenesis and up-regulated toll-like receptor-4-induced pathways were intimately associated with demyelination as measured by immunohistology. Conclusively, although transcriptional changes were dominated by the adaptive immune response, the main pathways associated with demyelination included up-regulation of toll-like receptor 4 and down-regulation of cholesterol biosynthesis. Cholesterol biosynthesis is a rate limiting step of myelination and its down-regulation is suggested to be involved in chronic demyelination by an inhibition of remyelination.

  10. The topograpy of demyelination and neurodegeneration in the multiple sclerosis brain.

    PubMed

    Haider, Lukas; Zrzavy, Tobias; Hametner, Simon; Höftberger, Romana; Bagnato, Francesca; Grabner, Günther; Trattnig, Siegfried; Pfeifenbring, Sabine; Brück, Wolfgang; Lassmann, Hans

    2016-03-01

    Multiple sclerosis is a chronic inflammatory disease with primary demyelination and neurodegeneration in the central nervous system. In our study we analysed demyelination and neurodegeneration in a large series of multiple sclerosis brains and provide a map that displays the frequency of different brain areas to be affected by these processes. Demyelination in the cerebral cortex was related to inflammatory infiltrates in the meninges, which was pronounced in invaginations of the brain surface (sulci) and possibly promoted by low flow of the cerebrospinal fluid in these areas. Focal demyelinated lesions in the white matter occurred at sites with high venous density and additionally accumulated in watershed areas of low arterial blood supply. Two different patterns of neurodegeneration in the cortex were identified: oxidative injury of cortical neurons and retrograde neurodegeneration due to axonal injury in the white matter. While oxidative injury was related to the inflammatory process in the meninges and pronounced in actively demyelinating cortical lesions, retrograde degeneration was mainly related to demyelinated lesions and axonal loss in the white matter. Our data show that accumulation of lesions and neurodegeneration in the multiple sclerosis brain does not affect all brain regions equally and provides the pathological basis for the selection of brain areas for monitoring regional injury and atrophy development in future magnetic resonance imaging studies.

  11. Intraocular Silicone Oil Masquerading as Terson Syndrome

    PubMed Central

    Samavat, Bijan; Mehrian, Payam; Hedayatfar, Alireza

    2016-01-01

    Introduction. Terson syndrome is described as intraocular hemorrhage in association with any type of intracranial hemorrhage and is associated with higher mortality rate and vision loss. Intraocular hemorrhage in Terson syndrome may be diagnosed using computed tomography but there are false positive results. Silicone oil which is widely used for internal tamponade of complicated retinal detachments has high attenuation on computed tomography and hyperintensity on T1-weighted magnetic resonance imaging that can mimic intraocular hemorrhage. This report shows that silicone oil is another origin of false positive results in interpreting CT findings for detecting Terson syndrome. Case Report. A 71-year-old diabetic woman presented with loss of consciousness. Brain computed tomography revealed right cerebellar hemorrhage and ventricular hemorrhage and hyperdensity in vitreous cavity of the left eye that was initially interpreted as vitreous hemorrhage. Terson syndrome was the initial diagnosis but ophthalmoscopic examination and brain MRI showed that the left eye had silicone oil tamponade. Conclusion. Without knowing the history of previous vitreoretinal surgery, CT scan findings of intraocular silicone oil may be interpreted as vitreous hemorrhage. In patients with concomitant intracranial hemorrhage, it can masquerade as Terson syndrome. PMID:27747119

  12. Tinea corporis masquerading as subacute cutaneous lupus erythematosus.

    PubMed

    Modi, Gunjan M; Maender, Jennifer L; Coleman, Neil; Hsu, Sylvia

    2008-04-15

    Few papers discuss the potential challenge of differentiating dermatophytosis from subacute cutaneous lupus erythematosus. This masquerade, most often manifest on the face, is of both clinical and therapeutic importance. We report a patient whose extensive tinea corporis very closely mimicked SCLE. The threshold for biopsy should be low in cases that exhibit atypical features for either of these entities.

  13. Cervical perineural cyst masquerading as a cervical spinal tumor.

    PubMed

    Joshi, Vijay P; Zanwar, Atul; Karande, Anuradha; Agrawal, Amit

    2014-04-01

    Tarlov (perineural) cysts of the nerve roots are common and usually incidental findings during magnetic resonance imaging of the lumbosacral spine. There are only a few case reports where cervical symptomatic perineural cysts have been described in the literature. We report such a case where a high cervical perineural cyst was masquerading as a cervical spinal tumor.

  14. Cervical Perineural Cyst Masquerading as a Cervical Spinal Tumor

    PubMed Central

    Joshi, Vijay P; Zanwar, Atul; Karande, Anuradha

    2014-01-01

    Tarlov (perineural) cysts of the nerve roots are common and usually incidental findings during magnetic resonance imaging of the lumbosacral spine. There are only a few case reports where cervical symptomatic perineural cysts have been described in the literature. We report such a case where a high cervical perineural cyst was masquerading as a cervical spinal tumor. PMID:24761204

  15. Fibronectin connecting segment-1 peptide inhibits pathogenic leukocyte trafficking and inflammatory demyelination in experimental models of chronic inflammatory demyelinating polyradiculoneuropathy.

    PubMed

    Dong, Chaoling; Greathouse, Kelsey M; Beacham, Rebecca L; Palladino, Steven P; Helton, E Scott; Ubogu, Eroboghene E

    2017-02-16

    The molecular determinants of pathogenic leukocyte migration across the blood-nerve barrier (BNB) in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) are unknown. Specific disease modifying therapies for CIDP are also lacking. Fibronectin connecting segment-1 (FNCS1), an alternatively spliced fibronectin variant expressed by microvascular endothelial cells at sites of inflammation in vitro and in situ, is a counterligand for leukocyte α4 integrin (also known as CD49d) implicated in pathogenic leukocyte trafficking in multiple sclerosis and inflammatory bowel disease. We sought to determine the role of FNCS1 in CIDP patient leukocyte trafficking across the BNB in vitro and in severe chronic demyelinating neuritis in vivo using a representative spontaneous murine CIDP model. Peripheral blood mononuclear leukocytes from 7 untreated CIDP patients were independently infused into a cytokine-treated, flow-dependent in vitro BNB model system. Time-lapse digital video microscopy was performed to visualize and quantify leukocyte trafficking, comparing FNCS1 peptide blockade to relevant controls. Fifty 24-week old female B7-2 deficient non-obese diabetic mice with spontaneous autoimmune peripheral polyneuropathy (SAPP) were treated daily with 2mg/kg FNCS1 peptide for 5days via intraperitoneal injection with appropriate controls. Neurobehavioral measures of disease severity, motor nerve electrophysiology assessments and histopathological quantification of inflammation and morphometric assessment of demyelination were performed to determine in vivo efficacy. The biological relevance of FNCS1 and CD49d in CIDP was evaluated by immunohistochemical detection in affected patient sural nerve biopsies. 25μM FNCS1 peptide maximally inhibited CIDP leukocyte trafficking at the human BNB in vitro. FNCS1 peptide treatment resulted in significant improvements in disease severity, motor electrophysiological parameters of demyelination and histological measures of

  16. ADAM12 is expressed by astrocytes during experimental demyelination.

    PubMed

    Baertling, Fabian; Kokozidou, Maria; Pufe, Thomas; Clarner, Tim; Windoffer, Reinhard; Wruck, Christoph J; Brandenburg, Lars-Ove; Beyer, Cordian; Kipp, Markus

    2010-04-22

    A disintegrin and metalloproteinase (ADAM) 12 represents a member of a large family of similarly structured multi-domain proteins. In the central nervous system (CNS), ADAM12 has been suggested to play a role in brain development, glioblastoma cell proliferation, and in experimental autoimmune encephalomyelitis. Furthermore, ADAM12 was reported to be almost exclusively expressed by oligodendrocytes and could, therefore, be considered as suitable marker for this cell type. In the present study, we investigated ADAM12 expression in the healthy and pathologically altered murine CNS. As pathological paradigm, we used the cuprizone demyelination model in which myelin loss during multiple sclerosis is imitated. Besides APC(+) oligodendrocytes, SMI311(+) neurons and GFAP(+) astrocytes express ADAM12 in the adult mouse brain. ADAM12 expression was further analyzed in vitro. After the induction of demyelination, we observed that activated astrocytes are the main source of ADAM12 in brain regions affected by oligodendrocyte loss. Exposure of astrocytes in vitro to either lipopolysaccharides (LPS), tumor necrosis factor alpha (TNFalpha), glutamate, or hydrogen peroxide revealed a highly stimulus-specific regulation of ADAM12 expression which was not seen in microglial BV2 cells. It appears that LPS- and TNFalpha-induced ADAM12 expression is mediated via the classic NFkappaB pathway. In summary, we demonstrated that ADAM12 is not a suitable marker for oligodendrocytes. Our results further suggest that ADAM12 might be implicated in the course of distinct CNS diseases such as demyelinating disorders.

  17. Analysis of the Host Transcriptome from Demyelinating Spinal Cord of Murine Coronavirus-Infected Mice

    PubMed Central

    Elliott, Ruth; Li, Fan; Dragomir, Isabelle; Chua, Ming Ming W.; Gregory, Brian D.; Weiss, Susan R.

    2013-01-01

    Persistent infection of the mouse central nervous system (CNS) with mouse hepatitis virus (MHV) induces a demyelinating disease pathologically similar to multiple sclerosis and is therefore used as a model system. There is little information regarding the host factors that correlate with and contribute to MHV-induced demyelination. Here, we detail the genes and pathways associated with MHV-induced demyelinating disease in the spinal cord. High-throughput sequencing of the host transcriptome revealed that demyelination is accompanied by numerous transcriptional changes indicative of immune infiltration as well as changes in the cytokine milieu and lipid metabolism. We found evidence that a Th1-biased cytokine/chemokine response and eicosanoid-derived inflammation accompany persistent MHV infection and that antigen presentation is ongoing. Interestingly, increased expression of genes involved in lipid transport, processing, and catabolism, including some with known roles in neurodegenerative diseases, coincided with demyelination. Lastly, expression of several genes involved in osteoclast or bone-resident macrophage function, most notably TREM2 and DAP12, was upregulated in persistently infected mouse spinal cord. This study highlights the complexity of the host antiviral response, which accompany MHV-induced demyelination, and further supports previous findings that MHV-induced demyelination is immune-mediated. Interestingly, these data suggest a parallel between bone reabsorption by osteoclasts and myelin debris clearance by microglia in the bone and the CNS, respectively. To our knowledge, this is the first report of using an RNA-seq approach to study the host CNS response to persistent viral infection. PMID:24058676

  18. Autotaxin and lysophosphatidic acid1 receptor-mediated demyelination of dorsal root fibers by sciatic nerve injury and intrathecal lysophosphatidylcholine

    PubMed Central

    2010-01-01

    Background Although neuropathic pain is frequently observed in demyelinating diseases such as Guillain-Barré syndrome and multiple sclerosis, the molecular basis for the relationship between demyelination and neuropathic pain behaviors is poorly understood. Previously, we found that lysophosphatidic acid receptor (LPA1) signaling initiates sciatic nerve injury-induced neuropathic pain and demyelination. Results In the present study, we have demonstrated that sciatic nerve injury induces marked demyelination accompanied by myelin-associated glycoprotein (MAG) down-regulation and damage of Schwann cell partitioning of C-fiber-containing Remak bundles in the sciatic nerve and dorsal root, but not in the spinal nerve. Demyelination, MAG down-regulation and Remak bundle damage in the dorsal root were abolished in LPA1 receptor-deficient (Lpar1-/-) mice, but these alterations were not observed in sciatic nerve. However, LPA-induced demyelination in ex vivo experiments was observed in the sciatic nerve, spinal nerve and dorsal root, all which express LPA1 transcript and protein. Nerve injury-induced dorsal root demyelination was markedly attenuated in mice heterozygous for autotaxin (atx+/-), which converts lysophosphatidylcholine (LPC) to LPA. Although the addition of LPC to ex vivo cultures of dorsal root fibers in the presence of recombinant ATX caused potent demyelination, it had no significant effect in the absence of ATX. On the other hand, intrathecal injection of LPC caused potent dorsal root demyelination, which was markedly attenuated or abolished in atx+/- or Lpar1-/- mice. Conclusions These results suggest that LPA, which is converted from LPC by ATX, activates LPA1 receptors and induces dorsal root demyelination following nerve injury, which causes neuropathic pain. PMID:21062487

  19. Dietary cholesterol promotes repair of demyelinated lesions in the adult brain

    PubMed Central

    Berghoff, Stefan A.; Gerndt, Nina; Winchenbach, Jan; Stumpf, Sina K.; Hosang, Leon; Odoardi, Francesca; Ruhwedel, Torben; Böhler, Carolin; Barrette, Benoit; Stassart, Ruth; Liebetanz, David; Dibaj, Payam; Möbius, Wiebke; Edgar, Julia M.; Saher, Gesine

    2017-01-01

    Multiple Sclerosis (MS) is an inflammatory demyelinating disorder in which remyelination failure contributes to persistent disability. Cholesterol is rate-limiting for myelin biogenesis in the developing CNS; however, whether cholesterol insufficiency contributes to remyelination failure in MS, is unclear. Here, we show the relationship between cholesterol, myelination and neurological parameters in mouse models of demyelination and remyelination. In the cuprizone model, acute disease reduces serum cholesterol levels that can be restored by dietary cholesterol. Concomitant with blood-brain barrier impairment, supplemented cholesterol directly supports oligodendrocyte precursor proliferation and differentiation, and restores the balance of growth factors, creating a permissive environment for repair. This leads to attenuated axon damage, enhanced remyelination and improved motor learning. Remarkably, in experimental autoimmune encephalomyelitis, cholesterol supplementation does not exacerbate disease expression. These findings emphasize the safety of dietary cholesterol in inflammatory diseases and point to a previously unrecognized role of cholesterol in promoting repair after demyelinating episodes. PMID:28117328

  20. The Biology of Persistent Infection: Inflammation and Demyelination following Murine Coronavirus Infection of the Central Nervous System

    PubMed Central

    Hosking, Martin P.; Lane, Thomas E.

    2009-01-01

    Multiple Sclerosis (MS) is an immune-mediated demyelinating disease of humans. Although causes of MS are enigmatic, underlying elements contributing to disease development include both genetic and environmental factors. Recent epidemiological evidence has pointed to viral infection as a trigger to initiating white matter damage in humans. Mouse hepatitis virus (MHV) is a positive strand RNA virus that, following intracranial infection of susceptible mice, induces an acute encephalomyelitis that later resolves into a chronic fulminating demyelinating disease. Immune cell infiltration into the central nervous system is critical both to quell viral replication and instigate demyelination. Recent efforts by our laboratory and others have focused upon strategies capable of enhancing remyelination in response to viral-induced demyelination, both by dampening chronic inflammation and by surgical engraftment of remyelination – competent neural precursor cells. PMID:19946572

  1. Vitamin D and estrogen synergy in Vdr-expressing CD4(+) T cells is essential to induce Helios(+)FoxP3(+) T cells and prevent autoimmune demyelinating disease.

    PubMed

    Spanier, Justin A; Nashold, Faye E; Mayne, Christopher G; Nelson, Corwin D; Hayes, Colleen E

    2015-09-15

    Multiple sclerosis (MS) is a neurodegenerative disease resulting from an autoimmune attack on the axon-myelin unit. A female MS bias becomes evident after puberty and female incidence has tripled in the last half-century, implicating a female sex hormone interacting with a modifiable environmental factor. These aspects of MS suggest that many female MS cases may be preventable. Mechanistic knowledge of this hormone-environment interaction is needed to devise strategies to reduce female MS risk. We previously demonstrated that vitamin D3 (D3) deficiency increases and D3 supplementation decreases experimental autoimmune encephalomyelitis (EAE) risk in a female-biased manner. We also showed that D3 acts in an estrogen (E2)-dependent manner, since ovariectomy eliminated and E2 restored D3-mediated EAE protection. Here we probed the hypothesis that E2 and D3 interact synergistically within CD4(+) T cells to control T cell fate and prevent demyelinating disease. The E2 increased EAE resistance in wild-type (WT) but not T-Vdr(0) mice lacking Vdr gene function in CD4(+) T cells, so E2 action depended entirely on Vdr(+)CD4(+) T cells. The E2 levels were higher in WT than T-Vdr(0) mice, suggesting the Vdr(+)CD4(+) T cells produced E2 or stimulated its production. The E2 decreased Cyp24a1 and increased Vdr transcripts in T cells, prolonging the calcitriol half-life and increasing calcitriol responsiveness. The E2 also increased CD4(+)Helios(+)FoxP3(+) T regulatory (Treg) cells in a Vdr-dependent manner. Thus, CD4(+) T cells have a cooperative amplification loop involving E2 and calcitriol that promotes CD4(+)Helios(+)FoxP3(+) Treg cell development and is disrupted when the D3 pathway is impaired. The global decline in population D3 status may be undermining a similar cooperative E2-D3 interaction controlling Treg cell differentiation in women, causing a breakdown in T cell self tolerance and a rise in MS incidence.

  2. Gut commensalism, cytokines, and central nervous system demyelination.

    PubMed

    Telesford, Kiel; Ochoa-Repáraz, Javier; Kasper, Lloyd H

    2014-08-01

    There is increasing support for the importance of risk factors such as genetic makeup, obesity, smoking, vitamin D insufficiency, and antibiotic exposure contributing to the development of autoimmune diseases, including human multiple sclerosis (MS). Perhaps the greatest environmental risk factor associated with the development of immune-mediated conditions is the gut microbiome. Microbial and helminthic agents are active participants in shaping the immune systems of their hosts. This concept is continually reinforced by studies in the burgeoning area of commensal-mediated immunomodulation. The clinical importance of these findings for MS is suggested by both their participation in disease and, perhaps of greater clinical importance, attenuation of disease severity. Observations made in murine models of central nervous system demyelinating disease and a limited number of small studies in human MS suggest that immune homeostasis within the gut microbiome may be of paramount importance in maintaining a disease-free state. This review describes three immunological factors associated with the gut microbiome that are central to cytokine network activities in MS pathogenesis: T helper cell polarization, T regulatory cell function, and B cell activity. Comparisons are drawn between the regulatory mechanisms attributed to first-line therapies and those described in commensal-mediated amelioration of central nervous system demyelination.

  3. Gut Commensalism, Cytokines, and Central Nervous System Demyelination

    PubMed Central

    Ochoa-Repáraz, Javier; Kasper, Lloyd H.

    2014-01-01

    There is increasing support for the importance of risk factors such as genetic makeup, obesity, smoking, vitamin D insufficiency, and antibiotic exposure contributing to the development of autoimmune diseases, including human multiple sclerosis (MS). Perhaps the greatest environmental risk factor associated with the development of immune-mediated conditions is the gut microbiome. Microbial and helminthic agents are active participants in shaping the immune systems of their hosts. This concept is continually reinforced by studies in the burgeoning area of commensal-mediated immunomodulation. The clinical importance of these findings for MS is suggested by both their participation in disease and, perhaps of greater clinical importance, attenuation of disease severity. Observations made in murine models of central nervous system demyelinating disease and a limited number of small studies in human MS suggest that immune homeostasis within the gut microbiome may be of paramount importance in maintaining a disease-free state. This review describes three immunological factors associated with the gut microbiome that are central to cytokine network activities in MS pathogenesis: T helper cell polarization, T regulatory cell function, and B cell activity. Comparisons are drawn between the regulatory mechanisms attributed to first-line therapies and those described in commensal-mediated amelioration of central nervous system demyelination. PMID:25084177

  4. The In Vivo PDGF Response During Remyelination in Mouse Spinal Cord Following Murine Hepatitis Virus Strain A59-Induced Transient Demyelination

    DTIC Science & Technology

    1998-09-14

    Mechanisms involved in myelin repair (remyelination) are poorly understood. This project examined changes in oligodendrocyte function during remyelination in the adult central nervous system (CNS). Knowledge of how oligodendrocytes remyelinate adult CNS may lead to therapies for chronic human demyelinating diseases such as multiple sclerosis (MS). In MS, demyelination is followed by partial, but incomplete remyelination.

  5. Mesenchymal stromal-cell transplants induce oligodendrocyte progenitor migration and remyelination in a chronic demyelination model.

    PubMed

    Jaramillo-Merchán, J; Jones, J; Ivorra, J L; Pastor, D; Viso-León, M C; Armengól, J A; Moltó, M D; Geijo-Barrientos, E; Martínez, S

    2013-08-29

    Demyelinating disorders such as leukodystrophies and multiple sclerosis are neurodegenerative diseases characterized by the progressive loss of myelin that may lead toward a chronic demyelination of the brain's white matter, impairing normal axonal conduction velocity and ultimately causing neurodegeneration. Current treatments modifying the pathological mechanisms are capable of ameliorating the disease; however, frequently, these therapies are not sufficient to repress the progressive demyelination into a chronic condition and permanent loss of function. To this end, we analyzed the effect that bone marrow-derived mesenchymal stromal cell (BM-MSC) grafts exert in a chronically demyelinated mouse brain. As a result, oligodendrocyte progenitors were recruited surrounding the graft due to the expression of various trophic signals by the grafted MSCs. Although there was no significant reaction in the non-grafted side, in the grafted regions oligodendrocyte progenitors were detected. These progenitors were derived from the nearby tissue as well as from the neurogenic niches, including the subependymal zone and dentate gyrus. Once near the graft site, the cells matured to myelinating oligodendrocytes. Finally, electrophysiological studies demonstrated that axonal conduction velocity was significantly increased in the grafted side of the fimbria. In conclusion, we demonstrate here that in chronic demyelinated white matter, BM-MSC transplantation activates oligodendrocyte progenitors and induces remyelination in the tissue surrounding the stem cell graft.

  6. Mesenchymal stromal-cell transplants induce oligodendrocyte progenitor migration and remyelination in a chronic demyelination model

    PubMed Central

    Jaramillo-Merchán, J; Jones, J; Ivorra, J L; Pastor, D; Viso-León, M C; Armengól, J A; Moltó, M D; Geijo-Barrientos, E; Martínez, S

    2013-01-01

    Demyelinating disorders such as leukodystrophies and multiple sclerosis are neurodegenerative diseases characterized by the progressive loss of myelin that may lead toward a chronic demyelination of the brain's white matter, impairing normal axonal conduction velocity and ultimately causing neurodegeneration. Current treatments modifying the pathological mechanisms are capable of ameliorating the disease; however, frequently, these therapies are not sufficient to repress the progressive demyelination into a chronic condition and permanent loss of function. To this end, we analyzed the effect that bone marrow-derived mesenchymal stromal cell (BM-MSC) grafts exert in a chronically demyelinated mouse brain. As a result, oligodendrocyte progenitors were recruited surrounding the graft due to the expression of various trophic signals by the grafted MSCs. Although there was no significant reaction in the non-grafted side, in the grafted regions oligodendrocyte progenitors were detected. These progenitors were derived from the nearby tissue as well as from the neurogenic niches, including the subependymal zone and dentate gyrus. Once near the graft site, the cells matured to myelinating oligodendrocytes. Finally, electrophysiological studies demonstrated that axonal conduction velocity was significantly increased in the grafted side of the fimbria. In conclusion, we demonstrate here that in chronic demyelinated white matter, BM-MSC transplantation activates oligodendrocyte progenitors and induces remyelination in the tissue surrounding the stem cell graft. PMID:23990019

  7. A rare presentation of atypical demyelination: tumefactive multiple sclerosis causing Gerstmann’s syndrome

    PubMed Central

    2014-01-01

    Background Tumefactive demyelinating lesions are a rare manifestation of multiple sclerosis (MS). Differential diagnosis of such space occupying lesions may not be straightforward and sometimes necessitate brain biopsy. Impaired cognition is the second most common clinical manifestation of tumefactive MS; however complex cognitive syndromes are unusual. Case presentation We report the case of a 30 year old woman who presented with Gerstmann’s syndrome. MRI revealed a large heterogeneous contrast enhancing lesion in the left cerebral hemisphere. Intravenous corticosteroids did not stop disease progression. A tumour or cerebral lymphoma was suspected, however brain biopsy confirmed inflammatory demyelination. Following diagnosis of tumefactive MS treatment with natalizumab effectively suppressed disease activity. Conclusions The case highlights the need for clinicians, radiologists and surgeons to appreciate the heterogeneous presentation of tumefactive MS. Early brain biopsy facilitates rapid diagnosis and management. Treatment with natalizumab may be useful in cases of tumefactive demyelination where additional evidence supports a diagnosis of relapsing MS. PMID:24694183

  8. [Multifocal demyelinating polyneuropathy with persistent conduction block (Lewis-Sumner syndrome)].

    PubMed

    Mezaki, T; Kaji, R; Hamano, T; Kimura, J; Kameyama, M

    1990-11-01

    Multifocal demyelinating neuropathy with persistent conduction block (Lewis-Sumner syndrome) is a variant of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), which often clinically simulates a motor neuron disease (MND). We report here three patients initially suspected to have MND, who later were diagnosed as a Lewis-Sumner syndrome. One of them showed a remarkable clinical improvement after immunoglobulin therapy. The definitive diagnosis of this syndrome rests upon nerve conduction studies, uncovering multiple sites of persistent conduction block. Technically, it is important to exclude insufficient stimulus which may lead to an erroneous impression of conduction block. Magnetic stimulation, as compared to electric current, elicited larger responses possibly because of deeper current penetration. We found this mode of stimulation useful especially in testing focal demyelination requiring full activation of a diseased nerve at a most proximal segment.

  9. Sphenoid sinus organized hematoma with cranial neuropathies masquerading as a malignancy: A case report

    PubMed Central

    LIN, YU-HSUAN; WANG, PO-CHIN; LIN, YAOH-SHIANG

    2016-01-01

    Sinonasal organized hematoma (SNOH) is rarely encountered in clinical practice. The disease demonstrates a high tendency for occurrence in East Asian individuals, and in the majority of cases, is located in the maxillary sinus. The current report presents the case of an 81-year-old female who developed a space-occupying lesion, which masqueraded as a skull base malignancy, following surgery for the treatment of isolated sphenoid sinus aspergilloma. Subsequent endoscopic endonasal surgery confirmed the diagnosis of an OH of the sphenoid sinus. The patient recovered from all neurological deficits within two months, with the exception of the loss of visual perception. Although SNOH presents a diagnostic challenge, when physicians possess knowledge of its typical imaging features, this facilitates the achievement of a correct diagnosis and the prescription of optimal treatment. PMID:27284357

  10. Sphenoid sinus organized hematoma with cranial neuropathies masquerading as a malignancy: A case report.

    PubMed

    Lin, Yu-Hsuan; Wang, Po-Chin; Lin, Yaoh-Shiang

    2016-06-01

    Sinonasal organized hematoma (SNOH) is rarely encountered in clinical practice. The disease demonstrates a high tendency for occurrence in East Asian individuals, and in the majority of cases, is located in the maxillary sinus. The current report presents the case of an 81-year-old female who developed a space-occupying lesion, which masqueraded as a skull base malignancy, following surgery for the treatment of isolated sphenoid sinus aspergilloma. Subsequent endoscopic endonasal surgery confirmed the diagnosis of an OH of the sphenoid sinus. The patient recovered from all neurological deficits within two months, with the exception of the loss of visual perception. Although SNOH presents a diagnostic challenge, when physicians possess knowledge of its typical imaging features, this facilitates the achievement of a correct diagnosis and the prescription of optimal treatment.

  11. Creatine Enhances Mitochondrial-Mediated Oligodendrocyte Survival After Demyelinating Injury

    PubMed Central

    Nanescu, Sonia E.

    2017-01-01

    Chronic oligodendrocyte loss, which occurs in the demyelinating disorder multiple sclerosis (MS), contributes to axonal dysfunction and neurodegeneration. Current therapies are able to reduce MS severity, but do not prevent transition into the progressive phase of the disease, which is characterized by chronic neurodegeneration. Therefore, pharmacological compounds that promote oligodendrocyte survival could be beneficial for neuroprotection in MS. Here, we investigated the role of creatine, an organic acid involved in adenosine triphosphate (ATP) buffering, in oligodendrocyte function. We found that creatine increased mitochondrial ATP production directly in oligodendrocyte lineage cell cultures and exerted robust protection on oligodendrocytes by preventing cell death in both naive and lipopolysaccharide-treated mixed glia. Moreover, lysolecithin-mediated demyelination in mice deficient in the creatine-synthesizing enzyme guanidinoacetate-methyltransferase (Gamt) did not affect oligodendrocyte precursor cell recruitment, but resulted in exacerbated apoptosis of regenerated oligodendrocytes in central nervous system (CNS) lesions. Remarkably, creatine administration into Gamt-deficient and wild-type mice with demyelinating injury reduced oligodendrocyte apoptosis, thereby increasing oligodendrocyte density and myelin basic protein staining in CNS lesions. We found that creatine did not affect the recruitment of macrophages/microglia into lesions, suggesting that creatine affects oligodendrocyte survival independently of inflammation. Together, our results demonstrate a novel function for creatine in promoting oligodendrocyte viability during CNS remyelination. SIGNIFICANCE STATEMENT We report that creatine enhances oligodendrocyte mitochondrial function and protects against caspase-dependent oligodendrocyte apoptosis during CNS remyelination. This work has important implications for the development of therapeutic targets for diseases characterized by

  12. A Case of Paraneoplastic Demyelinating Motor Polyneuropathy

    PubMed Central

    Mostoufizadeh, Sohrab; Souri, Maryam; de Seze, Jérôme

    2012-01-01

    Peripheral neuropathy is commonly accompanied by cancer but demyelinating ones are not commonly reported. We report the clinical, neurophysiological, and biological characteristics of an 82-year-old patient who presented with a demyelinating motor neuropathy and high titre of anti-ganglioside antibodies associated with oesophageal cancer. The neurological course worsened rapidly despite immunotherapy, leading to a bedridden status. We propose to suspect a paraneoplastic origin in older patients or when the clinical course progresses rapidly within a few weeks or months. PMID:22649345

  13. Metastatic Prostate Cancer to the Urethra Masquerading as Urothelial Carcinoma.

    PubMed

    Zardawi, Ibrahim; Chong, Peter

    2016-07-01

    Tumors of the urethra, whether primary or metastatic, are very rare. The true nature of urethral neoplasm is not always obvious clinically nor in routine histological sections. Immunostains should be performed on such lesions because of management implications. We present a case of multiple metastases to the urethra from a prostatic carcinoma, masquerading as multiple urothelial carcinomas. Pathologists and urologists should be aware of the possibility of metastasis from the prostate.

  14. Pleomorphic adenoma of the frontal sinus masquerading as a mucocele.

    PubMed

    Chew, Yok Kuan; Brito-Mutunayagam, Sushil; Chong, Aun Wee; Prepageran, Narayanan; Chandran, Patricia Ann; Khairuzzana, Baharudin; Lingham, Omkara Rubini

    2015-12-01

    Pleomorphic adenoma is the most common type of benign salivary gland tumor. It can also be found in the larynx, ear, neck, and nasal septum. It is rarely found in the maxillary sinus, and it has never been reported in the frontal sinus. We report a case of pleomorphic adenoma of the frontal sinus that masqueraded as a mucocele. We discuss the clinical presentation, diagnosis, and treatment of this patient, and we review the literature.

  15. Matrix metalloproteinase-12 deficiency ameliorates the clinical course and demyelination in Theiler's murine encephalomyelitis.

    PubMed

    Hansmann, Florian; Herder, Vanessa; Kalkuhl, Arno; Haist, Verena; Zhang, Ning; Schaudien, Dirk; Deschl, Ulrich; Baumgärtner, Wolfgang; Ulrich, Reiner

    2012-07-01

    Matrix metalloproteinases (MMPs) are a family of extracellular proteases involved in the pathogenesis of demyelinating diseases like multiple sclerosis (MS). The aim of the present study was to investigate whether MMPs induce direct myelin degradation, leukocyte infiltration, disruption of the blood-brain barrier (BBB), and/or extracellular matrix remodeling in the pathogenesis of Theiler's murine encephalomyelitis (TME), a virus-induced model of MS. During the demyelinating phase of TME, the highest transcriptional upregulation was detected for Mmp12, followed by Mmp3. Mmp12 (-/-) mice showed reduced demyelination, macrophage infiltration, and motor deficits compared with wild-type- and Mmp3 knock-out mice. However, BBB remained unaltered, and the amount of extracellular matrix deposition was similar in knock-out mice and wild-type mice. Furthermore, stereotaxic injection of activated MMP-3, -9, and -12 into the caudal cerebellar peduncle of adult mice induced a focally extensive primary demyelination prior to infiltration of inflammatory cells, as well as a reduction in the number of oligodendrocytes and a leakage of BBB. All these results demonstrate that MMP-12 plays an essential role in the pathogenesis of TME, most likely due to its primary myelin- or oligodendrocyte-toxic potential and its role in macrophage extravasation, whereas there was no sign of BBB damage or alterations to extracellular matrix remodeling/deposition. Thus, interrupting the MMP-12 cascade may be a relevant therapeutic approach for preventing chronic progressive demyelination.

  16. Unusual basal ganglia lesions in a diabetic uraemic patient proven to be demyelination: first pathological observation

    PubMed Central

    Tajima, Yasutaka; Mito, Yasunori; Yanai, Mituru; Fukazawa, Yu-ichiro

    2012-01-01

    A 64-year-old man suffering from diabetes mellitus and chronic renal failure was admitted to our hospital because of consciousness disturbance and parkinsonism. Cranial MRI showed very characteristic features involving the bilateral basal ganglia. Subsequent postmortem examinations demonstrated demyelination in the affected areas. These myelin destruction patterns were quite similar to those of central pontine myelinolysis. However, rapid correction of hyponatraemia was ruled out in this patient. Therefore, a new demyelinating brain disease associated with diabetes mellitus and chronic renal failure was suggested. PMID:22948993

  17. Contactin 1 IgG4 associates to chronic inflammatory demyelinating polyneuropathy with sensory ataxia.

    PubMed

    Miura, Yumako; Devaux, Jérôme J; Fukami, Yuki; Manso, Constance; Belghazi, Maya; Wong, Anna Hiu Yi; Yuki, Nobuhiro

    2015-06-01

    A Spanish group recently reported that four patients with chronic inflammatory demyelinating polyneuropathy carrying IgG4 autoantibodies against contactin 1 showed aggressive symptom onset and poor response to intravenous immunoglobulin. We aimed to describe the clinical and serological features of Japanese chronic inflammatory demyelinating polyneuropathy patients displaying the anti-contactin 1 antibodies. Thirteen of 533 (2.4%) patients with chronic inflammatory demyelinating polyneuropathy had anti-contactin 1 IgG4 whereas neither patients from disease or normal control subjects did (P = 0.02). Three of 13 (23%) patients showed subacute symptom onset, but all of the patients presented with sensory ataxia. Six of 10 (60%) anti-contactin 1 antibody-positive patients had poor response to intravenous immunoglobulin, whereas 8 of 11 (73%) antibody-positive patients had good response to corticosteroids. Anti-contactin 1 IgG4 antibodies are a possible biomarker to guide treatment option.

  18. In vitro analysis of the oligodendrocyte lineage in mice during demyelination and remyelination

    SciTech Connect

    Armstrong, R.; Friedrich, V.L. Jr.; Holmes, K.V.; Dubois-Dalcq, M. )

    1990-09-01

    A demyelinating disease induced in C57B1/6N mice by intracranial injection of a coronavirus (murine hepatitis virus strain A59) is followed by functional recovery and efficient CNS myelin repair. To study the biological properties of the cells involved in this repair process, glial cells were isolated and cultured from spinal cords of these young adult mice during demyelination and remyelination. Using three-color immunofluorescence combined with (3H)thymidine autoradiography, we have analyzed the antigenic phenotype and mitotic potential of individual glial cells. We identified oligodendrocytes with an antibody to galactocerebroside, astrocytes with an antibody to glial fibrillary acidic protein, and oligodendrocyte-type 2 astrocyte (O-2A) progenitor cells with the O4 antibody. Cultures from demyelinated tissue differed in several ways from those of age-matched controls: first, the total number of O-2A lineage cells was strikingly increased; second, the O-2A population consisted of a higher proportion of O4-positive astrocytes and cells of mixed oligodendrocyte-astrocyte phenotype; and third, all the cell types within the O-2A lineage showed enhanced proliferation. This proliferation was not further enhanced by adding PDGF, basic fibroblast growth factor (bFGF), or insulin-like growth factor I (IGF-I) to the defined medium. However, bFGF and IGF-I seemed to influence the fate of O-2A lineage cells in cultures of demyelinated tissue. Basic FGF decreased the percentage of cells expressing galactocerebroside. In contrast, IGF-I increased the relative proportion of oligodendrocytes. Thus, O-2A lineage cells from adult mice display greater phenotypic plasticity and enhanced mitotic potential in response to an episode of demyelination. These properties may be linked to the efficient remyelination achieved in this demyelinating disease.

  19. The diagnosis of multiple sclerosis and the various related demyelinating syndromes: a critical review.

    PubMed

    Karussis, Dimitrios

    2014-01-01

    Multiple sclerosis (MS), is a chronic disease of the central nervous system (CNS) characterized by loss of motor and sensory function, that results from immune-mediated inflammation, demyelination and subsequent axonal damage. MS is one of the most common causes of neurological disability in young adults. Several variants of MS (and CNS demyelinating syndromes in general) have been nowadays defined in an effort to increase the diagnostic accuracy, to identify the unique immunopathogenic profile and to tailor treatment in each individual patient. These include the initial events of demyelination defined as clinically or radiologically isolated syndromes (CIS and RIS respectively), acute disseminated encephalomyelitis (ADEM) and its variants (acute hemorrhagic leukoencephalitis-AHL, Marburg variant, and Balo's concentric sclerosis), Schilder's sclerosis, transverse myelitis, neuromyelitis optica (NMO and NMO spectrum of diseases), recurrent isolated optic neuritis and tumefactive demyelination. The differentiation between them is not only a terminological matter but has important implications on their management. For instance, certain patients with MS and prominent immunopathogenetic involvement of B cells and autoantibodies, or with the neuromyelitic variants of demyelination, may not only not respond well but even deteriorate under some of the first-line treatments for MS. The unique clinical and neuroradiological features, along with the immunological biomarkers help to distinguish these cases from classical MS. The use of such immunological and imaging biomarkers, will not only improve the accuracy of diagnosis but also contribute to the identification of the patients with CIS or RIS who, are at greater risk for disability progression (worse prognosis) or, on the contrary, will have a more benign course. This review summarizes in a critical way, the diagnostic criteria (historical and updated) and the definitions/characteristics of MS of the various variants

  20. [Target Molecule for a Demyelinating Type of Guillain-Barré Syndrome, Acute Inflammatory Demyelinating Polyneuropathy].

    PubMed

    Mori, Masahiro

    2015-11-01

    Guillain-Barré syndrome is classified into demyelinating type, acute inflammatory demyelinating polyneuropathy (AIDP) and axonal form, acute axonal motor neuropathy (AMAN). It has been clearly established that the target molecule for the former is a ganglioside. In contrast, despite years of effort, the target molecule for the latter has not been identified. Recently, molecules around the nodes of Ranvier have entered the spotlight, and "moesin" was reported to be a target molecule for cytomegalovirus associated-AIDP.

  1. [Chronic inflammatory demyelinating neuropathies and their variants

    PubMed

    Vallat, J.-M.; Tabaraud, F.; Magy, L.; Macian, F.

    2002-12-01

    The Chronic Inflammatory Demyelinating Polyradiculoneuropathies (CIDP) constitute a syndrome whose incidence is difficult to evaluate, and is probably underestimated. In the course of this presentation, we deliberately restricted discussion to issues raised in recent years concerning the extent of this syndrome. We discuss diagnostic criteria, especially electrophysiological ones. As the criteria proposed by the ad hoc committee of the American Academy of Neurology in 1991 have been questioned due to lack of sensitivity, new ones have been proposed recently. We briefly discuss the different types of chronic dysimmune demyelinating neuropathy: not only the CIDP, but also the Lewis and Sumner syndrome or multifocal inflammatory demyelinating neuropathy and the multiple conduction block neuropathies. At last, we point out the consistent finding of axonal involvement in the course of a chronic demyelinating neuropathy; over time, it can become predominant, which may make diagnosis difficult by suggesting a chronic axonal neuropathy that may be assumed to be primary. Consideration of these points may help clinicians recognize more chronic dysimmune neuropathies, for which immunosuppressive therapy has been found to be effective.

  2. Spatio-Temporal Patterns of Demyelination and Remyelination in the Cuprizone Mouse Model

    PubMed Central

    Tagge, Ian; O’Connor, Audrey; Chaudhary, Priya; Pollaro, Jim; Berlow, Yosef; Chalupsky, Megan; Bourdette, Dennis; Woltjer, Randy; Johnson, Mac; Rooney, William

    2016-01-01

    Cuprizone administration in mice provides a reproducible model of demyelination and spontaneous remyelination, and has been useful in understanding important aspects of human disease, including multiple sclerosis. In this study, we apply high spatial resolution quantitative MRI techniques to establish the spatio-temporal patterns of acute demyelination in C57BL/6 mice after 6 weeks of cuprizone administration, and subsequent remyelination after 6 weeks of post-cuprizone recovery. MRI measurements were complemented with Black Gold II stain for myelin and immunohistochemical stains for associated tissue changes. Gene expression was evaluated using the Allen Gene Expression Atlas. Twenty-five C57BL/6 male mice were split into control and cuprizone groups; MRI data were obtained at baseline, after 6 weeks of cuprizone, and 6 weeks post-cuprizone. High-resolution (100μm isotropic) whole-brain coverage magnetization transfer ratio (MTR) parametric maps demonstrated concurrent caudal-to-rostral and medial-to-lateral gradients of MTR decrease within corpus callosum (CC) that correlated well with demyelination assessed histologically. Our results show that demyelination was not limited to the midsagittal line of the corpus callosum, and also that opposing gradients of demyelination occur in the lateral and medial CC. T2-weighted MRI gray/white matter contrast was strong at baseline, weak after 6 weeks of cuprizone treatment, and returned to a limited extent after recovery. MTR decreases during demyelination were observed throughout the brain, most clearly in callosal white matter. Myelin damage and repair appear to be influenced by proximity to oligodendrocyte progenitor cell populations and exhibit an inverse correlation with myelin basic protein gene expression. These findings suggest that susceptibility to injury and ability to repair vary across the brain, and whole-brain analysis is necessary to accurately characterize this model. Whole-brain parametric mapping across

  3. Mitochondria as Crucial Players in Demyelinated Axons: Lessons from Neuropathology and Experimental Demyelination

    PubMed Central

    Campbell, Graham R.; Mahad, Don J.

    2011-01-01

    Mitochondria are the most efficient producers of energy in the form of ATP. Energy demands of axons, placed at relatively great distances from the neuronal cell body, are met by mitochondria, which when functionally compromised, produce reactive oxygen species (ROS) in excess. Axons are made metabolically efficient by myelination, which enables saltatory conduction. The importance of mitochondria for maintaining the structural integrity of myelinated axons is illustrated by neuroaxonal degeneration in primary mitochondrial disorders. When demyelinated, the compartmentalisation of ion channels along axons is disrupted. The redistribution of electrogenic machinery is thought to increase the energy demand of demyelinated axons. We review related studies that focus on mitochondria within unmyelinated, demyelinated and dysmyelinated axons in the central nervous system. Based on neuropathological observations we propose the increase in mitochondrial presence within demyelinated axons as an adaptive process to the increased energy need. An increased presence of mitochondria would also increase the capacity to produce deleterious agents such as ROS when functionally compromised. Given the lack of direct evidence of a beneficial or harmful effect of mitochondrial changes, the precise role of increased mitochondrial presence within axons due to demyelination needs to be further explored in experimental demyelination in-vivo and in-vitro. PMID:21331147

  4. Primary demyelination in transgenic mice expressing interferon-γ

    PubMed Central

    Mcgavern, Dorian B.; Rodriguez, Moses; Oldstone, Michael B.A.

    2017-01-01

    Ever since the use of interferon-γ to treat patients with multiple sclerosis resulted in enhanced disease, the role of IFN-γ in demyelinatlon has been under question. To address this issue directly, transgenic mice were generated that expressed the cDNA of murlne IFN-γ in the central nervous system by using an oligodendrocyte-specific promoter. Expression of the transgene occurred after 8 weeks of age, at which time the murlne immune and central nervous systems are both fully developed. Directly associated with transgene expression, primary demyelination occurred and was accompanied by clinical abnormalities consistent with CNS disorders. Additionally, multiple hallmarks of immune-mediated CNS disease were observed including upregulation of MHC molecules, gliosis and lymphocytlc infiltration. These results demonstrate a direct role for IFN-γ as an Inducer of CNS demyellnatlon leading to disease and provide new opportunities for dissecting the mechanism of demyelinatlon. PMID:9288735

  5. Cuprizone demyelination of the corpus callosum in mice correlates with altered social interaction and impaired bilateral sensorimotor coordination.

    PubMed

    Hibbits, Norah; Pannu, Ravinder; Wu, T John; Armstrong, Regina C

    2009-08-14

    For studies of remyelination in demyelinating diseases, the cuprizone model of CC (corpus callosum) demyelination has experimental advantages that include overall size, proximity to neural stem cells of the subventricular zone, and correlation with a lesion predilection site in multiple sclerosis. In addition, cuprizone treatment can be ended to allow more direct analysis of remyelination than with viral or autoimmune models. However, CC demyelination lacks a useful functional correlate in rodents for longitudinal analysis throughout the course of demyelination and remyelination. In the present study, we tested two distinct behavioural measurements in mice fed 0.2% cuprizone. Running on a 'complex' wheel with varied rung intervals requires integration between cerebral hemispheres for rapid bilateral sensorimotor coordination. Maximum running velocity on the 'complex' wheel decreased during acute (6 week) and chronic (12 week) cuprizone demyelination. Running velocity on the complex wheel distinguished treated (for 6 weeks) from non-treated mice, even after a 6-week recovery period for spontaneous remyelination. A second behavioural assessment was a resident-intruder test of social interaction. The frequency of interactive behaviours increased among resident mice after acute or chronic demyelination. Differences in both sensorimotor coordination and social interaction correlated with demonstrated CC demyelination. The wheel assay is applicable for longitudinal studies. The resident-intruder assay provides a complementary assessment of a distinct modality at a specific time point. These behavioural measurements are sufficiently robust for small cohorts as a non-invasive assessment of demyelination to facilitate analysis of subsequent remyelination. These measurements may also identify CC involvement in other mouse models of central nervous system injuries and disorders.

  6. A novel model of demyelination and remyelination in a GFP-transgenic zebrafish

    PubMed Central

    Fang, Yangwu; Lei, Xudan; Li, Xiang; Chen, Yanan; Xu, Fei; Feng, Xizeng; Wei, Shihui; Li, Yuhao

    2015-01-01

    ABSTRACT Demyelinating diseases consist of a variety of autoimmune conditions in which the myelin sheath is damaged due to genetic and/or environmental factors. During clinical treatment, some patients undergo partial remyelination, especially during the early disease stages. However, the mechanisms that regulate demyelination remain unclear. The myelin structure, myelin formation and myelin-related gene expression are highly conserved between mammals and zebrafish. Therefore, the zebrafish is an ideal model organism to study myelination. In this study, we generated a transgenic zebrafish Tg(mbp:nfsB-egfp) expressing a fusion protein composed of enhanced green fluorescent protein (EGFP) and NTR from the myelin basic protein (mbp) promoter. Tg(mbp:nfsB-egfp) expressed NTR-EGFP reproducibly and hereditarily in oligodendrocytes along the spinal cord. Treatment of zebrafish larvae Tg(mbp:nfsB-egfp) with metronidazole (Mtz) resulted in the selective ablation of oligodendrocytes and led to demyelination, accompanied by behavioral changes, including decreased total movement distance, velocity, total movement time and fast movement time. After withdrawal of Mtz for a seven day recovery period, the expression of EGFP and MBP protein was observed again which indicates remyelination. Additionally, locomotor capacity was restored. Collectively, Tg(mbp:nfsB-egfp), a heritable and stable transgenic line, provides a novel, powerful tool to study the mechanisms of demyelination and remyelination. PMID:25527642

  7. Meningeal inflammation and demyelination in a patient clinically diagnosed with acute disseminated encephalomyelitis.

    PubMed

    Koshihara, Hiroshi; Oguchi, Kenya; Takei, Yo-ichi; Kitazawa, Kazuo; Higuchi, Kayoko; Ohara, Shinji

    2014-11-15

    Acute disseminated encephalomyelitis (ADEM) and multiple sclerosis (MS) are both CNS inflammatory demyelinating diseases with overlapping clinical features. A case is reported of a 51-year-old female who presented with headache, progressive aphasia and hemiparesis without preceding infection or vaccination. Brain MRI revealed multiple, often confluent, subcortical white matter lesions without enhancement, affecting predominantly the left cerebral hemisphere. CSF examination failed to reveal oligoclonal bands. Brain biopsy revealed both pathological features of ADEM and findings are consistent with the early stage of MS, including meningeal B and T lymphocytic infiltration, perivenular demyelination, subpial demyelination and discrete confluent plaque-like foci of demyelination. Steroid treatment resulted in remarkable clinical and radiological improvement and there has been no recurrence in six years of follow-up. This case highlights the difficulties in differentiating between ADEM and the first attack of MS and further suggests that ADEM and the early stage of MS, and its tumefactive variant, may have a common underlying pathologic mechanism, which may have a therapeutic implication in treating these diseases.

  8. [Pathogenesis of chronic inflammatory demyelinating polyneuropathy].

    PubMed

    Aranami, Toshimasa; Yamamura, Takashi

    2013-05-01

    Chronic inflammatory demyelinating polyneuropathy (CIDP) is considered to be a demyelinating autoimmune disorder in the peripheral nervous system. Concerning cellular immune response, activity of IFN-gamma producing Th1 and IL-17 producing Th17 cells might be accelerated in patients with CIDP, while regulatory function of CD4+ CD25(high) Foxp3+ regulatory T cells might be diminished. Humoral immune responses against several myelin components such as myelin protein zero and gangliosides such as GM1 might be also induced in a part of patients with CIDP. Besides, growing body of evidences suggest that immune response against several molecules expressed in the noncompact myelin might be involved in the pathogenesis of CIDP.

  9. Invasive Ocular Surface Squamous Neoplasia Masquerading as Nodular Scleritis.

    PubMed

    Sharma, Medha; Sundar, Dheepak; Vanathi, Murugesan; Meel, Rachna; Kashyap, Seema; Chawla, Rohan; Tandon, Radhika

    The authors report a rare case of ocular surface squamous neoplasia with intraocular involvement that had an initial masquerade presentation of recurrent anterior nodular scleritis. A 35-year-old male patient presented with right eye recurrent anterior nodular scleritis for which a lamellar patch graft was done. Two months later, the patient presented with recurrence of symptoms. Histopathology review revealed the presence of well-differentiated squamous cell malignancy. A high index of suspicion for malignancy is required in such cases when they do not respond to conventional therapy.

  10. Predators are less likely to misclassify masquerading prey when their models are present

    PubMed Central

    Skelhorn, John; Ruxton, Graeme D.

    2010-01-01

    Masquerading animals have evolved striking visual resemblances to inanimate objects. These animals gain protection from their predators not simply by avoiding detection, but by causing their predators to misclassify them as the ‘models’ that they appear to resemble. Using domestic chicks as predators and twig-mimicking caterpillars as prey, we demonstrated that masquerading prey were more likely to be misclassified as their models when viewed in isolation from their models than when viewed alongside examples of their model, although they benefitted from masquerade to some extent in both conditions. From this, we predict a selection pressure on masqueraders to use microhabitats that reduce the risk of them being viewed simultaneously with examples of their model, and/or to more closely resemble their model in situations where simultaneous viewing is commonplace. PMID:20410028

  11. Acute clinical onset chronic inflammatory demyelinating polyneuropathy in a dog.

    PubMed

    Molín, Jéssica; Márquez, Mercedes; Raurell, Xavier; Matiasek, Kaspar; Ferrer, Isidre; Pumarola, Martí

    2011-09-01

    We report a case of acute-onset ambulatory paraparesis with electrophysiological abnormalities compatible with axonal and demyelinating lesions in a Rottweiler dog. Although the clinical findings were compatible with acute canine idiopathic polyneuropathy, postmortem investigations revealed a chronic demyelinating polyneuropathy affecting the nerve roots. Due to the combination of acute clinical presentation and chronic pathologic features, this case is consistent with the acute-onset form of chronic inflammatory demyelinating polyneuropathy (A-CIDP).

  12. Roles of an extracellular matrix (ECM) receptor and ECM processing enzymes in demyelinating canine distemper encephalitis.

    PubMed

    Alldinger, S; Gröters, S; Miao, Q; Fonfara, S; Kremmer, E; Baumgärtner, W

    2006-04-01

    Canine distemper virus (CDV) belongs to the genus Morbillivirus of the Paramyxoviridae family. Due to the central nervous system (CNS) tropism of the virus and associated neuropathological changes, demyelinating canine distemper encephalitis (CDE) represents a relevant model for human demyelinating diseases like multiple sclerosis. The present review decribes the role of CD44 antigen (CD44), the principle cell surface receptor for hyaluronate and extracellular matrix (ECM) processing enzymes (matrix metalloproteinases [MMPs]) and their inhibitors (TIMPs) in the pathogenesis of demyelination. In acute and subacute CDE, a plaque-associated CD44 up-regulation is found that parallels astrocyte activation. Likewise, MMPs and TIMPs are prominently up-regulated in these lesions and are expressed mostly by astrocytes and microglia. In chronic lesions, CD44 expression declines together with the number of glial fibrillary acidic protein (GFAP) positive astrocytes. In addition, in this plaque type, CD44 is expressed on the cell membrane of perivascular mononuclear cells. In this phase, a decrease of MMP and TIMP expressions apart from MMP-11, -12, and -13 is obvious. In summary, CD44 and MMPs might be associated with the onset of demyelination and may interact to initiate ECM disturbances. Ligation of CD44 in the early phase may induce chemokines and cytokines and hence initiate and perpetuate the inflammatory process. In the chronic phase, it is conceivable that a MMP-TIMP imbalance may be the motor for lesion progression with a simultaneous influx of CD44-positive activated immune cells.

  13. Oligodendrocyte Lineage Cells in Chronic Demyelination of Multiple Sclerosis Optic Nerve.

    PubMed

    Jennings, Alison Ruth; Carroll, William M

    2015-09-01

    Reports that chronically demyelinated multiple sclerosis brain and spinal cord lesions contained immature oligodendrocyte lineage cells have generated major interest aimed at the potential for promotion of endogenous repair. Despite the prominence of the optic nerve as a lesion site and its importance in clinical disease assessment, no detailed studies of multiple sclerosis-affected optic nerve exist. This study aims to provide insight into the cellular pathology of chronic demyelination in multiple sclerosis through direct morphological and immunohistochemical analysis of optic nerve in conjunction with observations from an experimental cat optic nerve model of successful remyelination. Myelin staining was followed by immunohistochemistry to differentially label neuroglia. Digitally immortalized sections were then analyzed to generate quantification data and antigenic phenotypes including maturational stages within the oligodendrocyte lineage. It was found that some chronically demyelinated multiple sclerosis optic nerve lesions contained oligodendroglial cells and that heterogeneity existed in the presence of myelin sheaths, oligodendrocyte maturational stages and extent of axonal investment. The findings advance our understanding of oligodendrocyte activity in chronically demyelinated human optic nerve and may have implications for studies aimed at enhancement of endogenous repair in multiple sclerosis.

  14. Loss of Saltation and Presynaptic Action Potential Failure in Demyelinated Axons

    PubMed Central

    Hamada, Mustafa S.; Popovic, Marko A.; Kole, Maarten H. P.

    2017-01-01

    In cortical pyramidal neurons the presynaptic terminals controlling transmitter release are located along unmyelinated axon collaterals, far from the original action potential (AP) initiation site, the axon initial segment (AIS). Once initiated, APs will need to reliably propagate over long distances and regions of geometrical inhomogeneity like branch points (BPs) to rapidly depolarize the presynaptic terminals and confer temporally precise synaptic transmission. While axon pathologies such as demyelinating diseases are well established to impede the fidelity of AP propagation along internodes, to which extent myelin loss affects propagation along BPs and axon collaterals is not well understood. Here, using the cuprizone demyelination model, we performed optical voltage-sensitive dye (VSD) imaging from control and demyelinated layer 5 pyramidal neuron axons. In the main axon, we find that myelin loss switches the modality of AP propagation from rapid saltation towards a slow continuous wave. The duration of single AP waveforms at BPs or nodes was, however, only slightly briefer. In contrast, by using two-photon microscopy-guided loose-seal patch recordings from axon collaterals we revealed a presynaptic AP broadening in combination with a reduced velocity and frequency-dependent failure. Finally, internodal myelin loss was also associated with de novo sprouting of axon collaterals starting from the primary (demyelinated) axon. Thus, the loss of oligodendrocytes and myelin sheaths bears functional consequences beyond the main axon, impeding the temporal fidelity of presynaptic APs and affecting the functional and structural organization of synaptic connectivity within the neocortex. PMID:28289377

  15. [Subcutaneous immunoglobulin. Treatment in chronic inflammatory demyelinating polyradiculo-neuropathy].

    PubMed

    Nogués, Martín A; Varela, Francisco J; Seminario, Gisela; Insúa, María C; Bezrodnik, Liliana

    2016-01-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an acquired disease that may affect nerve roots and peripheral nerves. Despite its low incidence, diagnosis is particularly important because there are different effective treatments. Human immunoglobulin is one of the mainstays of the treatment. Although there are few studies up to date, subcutaneous immunoglobulin (IgSC) has been proposed as an alternative to intravenous administration with similar efficacy. We present three cases with definite CIDP, classified according to the European Federation of Neurological Societies / Peripheral Nerve, Society (EFNS /PNS) criteria in which was used SCIgG as a treatment after success with the intravenous route. The Overall Neuropathy Limitations Scale (ONLS) was used to estimate the changes in the muscular strength before and after treatment.

  16. [On the mechanisms and diagnosis of conduction disturbances due to demyelination with special reference to multifocal demyelinating neuropathy (Lewis-Sumner)].

    PubMed

    Kaji, R; Kimura, J

    1991-12-01

    Multifocal demyelinating neuropathy with persistent conduction block can mimic motor neuron disease, but is potentially reversible. Its diagnosis rests upon electrophysiological demonstration of focal conduction block at multiple sites. Conduction block is the most important mechanism causing clinical symptoms in peripheral nerve demyelination. On the other hand, conduction slowing is not always associated with clinical symptoms. In 2 out of 9 patients with multifocal demyelinating motor neuropathy, MRI showed focal swelling of the nerve at the site of conduction block. Both of them had elevated titers of anti-GM1 antibodies. In one, we biopsied a portion of the medial pectoral nerve, which was adjacent to the focal swelling, at surgical exploration. Pathological findings included very thin myelin associated with large diameter fibers and small onion bulb formation, suggesting that remyelinative process is abortive in this disease leading to persistent conduction block. Anti-GM1 antibodies bound to the denuded axoplasmic membrane may interfere with the process by masking the cell surface markers. The reason why the sensory fibers are spared is unclear, but it may be possible that GM1 in sensory axons have less affinity to the antibody than that in motor fibers.

  17. Molecular Mechanisms of Inherited Demyelinating Neuropathies

    PubMed Central

    SCHERER, STEVEN S.; WRABETZ, LAWRENCE

    2008-01-01

    The past 15 years have witnessed the identification of more than 25 genes responsible for inherited neuropathies in humans, many associated with primary alterations of the myelin sheath. A remarkable body of work in patients, as well as animal and cellular models, has defined the clinical and molecular genetics of these illnesses and shed light on how mutations in associated genes produce the heterogeneity of dysmyelinating and demyelinating phenotypes. Here, we review selected recent developments from work on the molecular mechanisms of these disorders and their implications for treatment strategies. PMID:18803325

  18. Asymmetric type F botulism with cranial nerve demyelination.

    PubMed

    Filozov, Alina; Kattan, Jessica A; Jitendranath, Lavanya; Smith, C Gregory; Lúquez, Carolina; Phan, Quyen N; Fagan, Ryan P

    2012-01-01

    We report a case of type F botulism in a patient with bilateral but asymmetric neurologic deficits. Cranial nerve demyelination was found during autopsy. Bilateral, asymmetric clinical signs, although rare, do not rule out botulism. Demyelination of cranial nerves might be underrecognized during autopsy of botulism patients.

  19. Paraneoplastic tumefactive demyelination with underlying combined germ cell cancer.

    PubMed

    Broadfoot, Jack R; Archer, Hilary A; Coulthard, Elizabeth; Appelman, Auke P A; Sutak, Judit; Braybrooke, Jeremy P; Love, Seth

    2015-12-01

    Paraneoplastic demyelination is a rare disorder of the central nervous system. We describe a 60-year-old man with tumefactive demyelination who had an underlying retroperitoneal germ cell cancer. He presented with visuospatial problems and memory loss and had a visual field defect. His MRI was interpreted as a glioma but stereotactic biopsy showed active demyelination. Investigation for multiple sclerosis was negative but CT imaging showed retroperitoneal lymphadenopathy, and nodal biopsy confirmed a combined germ cell cancer. He responded poorly to corticosteroid treatment, and his visual field defect progressed. However, 6 months after plasma exchange and successful chemotherapy, he has partially improved clinically and radiographically. Tumefactive demyelination is typically associated with multiple sclerosis but may be paraneoplastic. It is important to recognise paraneoplastic tumefactive demyelination early, as the neurological outcome relies on treating the associated malignancy.

  20. Treatment of chronic inflammatory demyelinating polyneuropathy.

    PubMed

    Kleyman, Inna; Brannagan, Thomas H

    2015-07-01

    Chronic inflammatory demyelinating polyneuropathy (CIDP) is one of the acquired demyelinating neuropathies and is considered to be immune mediated. Diagnosis is typically based on clinical history, neurologic examination, electrophysiologic studies, CSF studies, and pathologic examination. Early diagnosis and treatment is important to prevent irreversible axonal loss and optimize improvement in function. The first-line agents for treatment are intravenous immunoglobulin (IVIg), corticosteroids, and plasmapheresis, which have all been demonstrated to be effective in controlled studies. Studies have not shown a significant difference between these three treatments, and the initial choice of therapy is often based on availability, cost, ease of administration, and side effect profile. If patients do not respond to one of these agents, they may respond to one of the others and sometimes in combination. If the first-line agents are not effective, chemotherapeutic or immunosuppressive agents may be considered. There are limited controlled studies of these modalities, and they are often used in conjunction with a first-line treatment. The majority of patients require long-term therapy to maintain a response and to prevent relapse.

  1. Protective Effect of a cAMP Analogue on Behavioral Deficits and Neuropathological Changes in Cuprizone Model of Demyelination.

    PubMed

    Vakilzadeh, Gelareh; Khodagholi, Fariba; Ghadiri, Tahereh; Darvishi, Marzieh; Ghaemi, Amir; Noorbakhsh, Farshid; Gorji, Ali; Sharifzadeh, Mohammad

    2015-08-01

    Multiple sclerosis (MS) is an inflammatory demyelinating disease that leads to neuronal cell loss. Cyclic AMP and its analogs are well known to decrease inflammation and apoptosis. In the present study, we examined the effects of bucladesine, a cell-permeable analogue of cyclic adenosine monophosphate (cAMP), on myelin proteins (PLP, PMP-22), inflammation, and apoptotic, as well as anti-apoptotic factors in cuprizone model of demyelination. C57BL/6J mice were fed with chow containing 0.2% copper chelator cuprizone or vehicle by daily oral gavage for 5 weeks to induce reversible demyelination predominantly of the corpus callosum. Bucladesine was administered intraperitoneally at different doses (0.24, 0.48, or 0.7 μg/kg body weight) during the last 7 days of 5-week cuprizone treatment. Bucladesine exhibited a protective effect on myelination. Furthermore, bucladesine significantly decreased the production of interleukin-6 pro-inflammatory mediator as well as nuclear factor-κB activation and reduced the mean number of apoptotic cells compared to cuprizone-treated mice. Bucladesine also decreased production of caspase-3 as well as Bax and increased Bcl-2 levels. Our data revealed that enhancement of intracellular cAMP prevents demyelination and plays anti-inflammatory and anti-apoptotic properties in mice cuprizone model of demyelination. This suggests the modulation of intracellular cAMP as a potential target for treatment of MS.

  2. Acute parkinsonian syndrome with demyelinating leukoencephalopathy in bone marrow transplant recipients.

    PubMed

    Lockman, L A; Sung, J H; Krivit, W

    1991-01-01

    A syndrome of rigidity, bradykinesia, spasticity, and often myoclonus and dementia developed acutely in 5 patients who had undergone successful engraftment of bone marrow transplants for the treatment of various hematologic diseases. Magnetic resonance imaging demonstrated widespread changes in white matter; brain biopsy disclosed mild demyelination associated with active phagocytosis of myelin. One patient, who was not treated, remains severely demented. Patients treated with very high-dose methylprednisolone had complete clinical recovery.

  3. Small bowel endometriosis masquerading as regional enteritis.

    PubMed

    Minocha, A; Davis, M S; Wright, R A

    1994-05-01

    A 35-year-old female presented with recurrent right lower quadrant pain, nausea, and vomiting. She was afebrile with diffuse abdominal tenderness. Plain x-ray of abdomen revealed small bowel obstruction. A barium x-ray of the small bowel showed stricture of the terminal ileum. A CT scan of the abdomen showed a 6-cm mass in right lower quadrant. She was empirically managed as having Crohn's disease. She underwent laparotomy after failure of medical management with high-dose steroids. There was ulceration and narrowing of terminal ileum. Frozen sections revealed endometriosis. Ileocecectomy was performed. Histopathology of resected specimen confirmed the diagnosis of endometriosis, and there was no evidence of chronic inflammatory bowel disease or neoplasia. Ileal endometriosis should be considered in the differential diagnosis of Crohn's disease in menstruating females presenting with perimenstrual symptoms.

  4. CXCL10 and trafficking of virus-specific T cells during coronavirus-induced demyelination

    PubMed Central

    Stiles, Linda N.; Liu, Michael T.; Kane, Joy A. C.; Lane, Thomas E.

    2009-01-01

    Chronic expression of CXC chemokine ligand 10 (CXCL10) in the central nervous system (CNS) following infection with the neurotropic JHM strain of mouse hepatitis virus (JHMV) is associated with an immune-mediated demyelinating disease. Treatment of mice with anti-CXCL10 neutralizing antibody results in limited CD4+ T cell infiltration into the CNS accompanied by a reduction in white matter damage. The current study determines the antigen-specificity of the T lymphocytes present during chronic disease and evaluates how blocking CXCL10 signaling affects retention of virus-specific T cells within the CNS. CXCL10 neutralization selectively reduced accumulation and/or retention of virus-specific CD4+ T cells, yet exhibited limited effect on virus-specific CD8+ T cells. The response of CXCL10 neutralization on virus-specific T cell subsets is not due to differential expression of the CXCL10 receptor CXCR3 on T cells as there was no appreciable difference in receptor expression on virus-specific T cells during either acute or chronic disease. These findings emphasize the importance of virus-specific CD4+ T cells in amplifying demyelination in JHMV-infected mice. In addition, differential signals are required for trafficking and retention of virus-specific CD4+ and CD8+ T cells during chronic demyelination in JHMV-infected mice. PMID:19626487

  5. Primary Cutaneous Histoplasmosis Masquerading as Lepromatous Leprosy

    PubMed Central

    Rani, Poonam; Aggarwal, Radhika; Kaushal, Seema

    2017-01-01

    Histoplasmosis is a genus of dimorphic fungi having various varieties of which the commonest one causing infection is Histoplasma capsulatum known to cause histoplasmosis. It has a varied disease spectrum ranging from an acute infection to chronic disease especially in lungs, disseminated disease and cutaneous disorder. Histoplasma capsulatum usually causes subclinical infection and serious infections only manifest in immunocompromised patients. Frank cases of infection are seen in pulmonary histoplasmosis. The spores of these organisms are seen to be strongly associated with droppings of birds and bats. A combination of these droppings and some soil types provide for an excellent environment for the proliferation of spores. Pulmonary histoplasmosis and disseminated disease are very common in AIDS patients and are a great cause of morbidity and mortality in these patients. Primary cutaneous histoplasmosis is very rare and occurs due to penetrating injuries. Once diagnosis is made, the lesions respond very well to oral itraconazole, fluconazole or amphotericicn B. We report a rare case of Cutaneous Histoplasmosis (CHP) in a 70-year-old male with complaints of multiple nodules all over his body in a HIV seronegative and otherwise immunocompetent patient. PMID:28273974

  6. Identifying and quantifying recurrent novae masquerading as classical novae

    SciTech Connect

    Pagnotta, Ashley; Schaefer, Bradley E.

    2014-06-20

    Recurrent novae (RNe) are cataclysmic variables with two or more nova eruptions within a century. Classical novae (CNe) are similar systems with only one such eruption. Many of the so-called CNe are actually RNe for which only one eruption has been discovered. Since RNe are candidate Type Ia supernova progenitors, it is important to know whether there are enough in our Galaxy to provide the supernova rate, and therefore to know how many RNe are masquerading as CNe. To quantify this, we collected all available information on the light curves and spectra of a Galactic, time-limited sample of 237 CNe and the 10 known RNe, as well as exhaustive discovery efficiency records. We recognize RNe as having (1) outburst amplitude smaller than 14.5 – 4.5 × log (t {sub 3}), (2) orbital period >0.6 days, (3) infrared colors of J – H > 0.7 mag and H – K > 0.1 mag, (4) FWHM of Hα > 2000 km s{sup –1}, (5) high excitation lines, such as Fe X or He II near peak, (6) eruption light curves with a plateau, and (7) white dwarf mass greater than 1.2 M {sub ☉}. Using these criteria, we identify V1721 Aql, DE Cir, CP Cru, KT Eri, V838 Her, V2672 Oph, V4160 Sgr, V4643 Sgr, V4739 Sgr, and V477 Sct as strong RN candidates. We evaluate the RN fraction among the known CNe using three methods to get 24% ± 4%, 12% ± 3%, and 35% ± 3%. With roughly a quarter of the 394 known Galactic novae actually being RNe, there should be approximately a hundred such systems masquerading as CNe.

  7. The quality of cortical network function recovery depends on localization and degree of axonal demyelination.

    PubMed

    Cerina, Manuela; Narayanan, Venu; Göbel, Kerstin; Bittner, Stefan; Ruck, Tobias; Meuth, Patrick; Herrmann, Alexander M; Stangel, Martin; Gudi, Viktoria; Skripuletz, Thomas; Daldrup, Thiemo; Wiendl, Heinz; Seidenbecher, Thomas; Ehling, Petra; Kleinschnitz, Christoph; Pape, Hans-Christian; Budde, Thomas; Meuth, Sven G

    2017-01-01

    Myelin loss is a severe pathological hallmark common to a number of neurodegenerative diseases, including multiple sclerosis (MS). Demyelination in the central nervous system appears in the form of lesions affecting both white and gray matter structures. The functional consequences of demyelination on neuronal network and brain function are not well understood. Current therapeutic strategies for ameliorating the course of such diseases usually focus on promoting remyelination, but the effectiveness of these approaches strongly depends on the timing in relation to the disease state. In this study, we sought to characterize the time course of sensory and behavioral alterations induced by de- and remyelination to establish a rational for the use of remyelination strategies. By taking advantage of animal models of general and focal demyelination, we tested the consequences of myelin loss on the functionality of the auditory thalamocortical system: a well-studied neuronal network consisting of both white and gray matter regions. We found that general demyelination was associated with a permanent loss of the tonotopic cortical organization in vivo, and the inability to induce tone-frequency-dependent conditioned behaviors, a status persisting after remyelination. Targeted, focal lysolecithin-induced lesions in the white matter fiber tract, but not in the gray matter regions of cortex, were fully reversible at the morphological, functional and behavioral level. These findings indicate that remyelination of white and gray matter lesions have a different functional regeneration potential, with the white matter being able to regain full functionality while cortical gray matter lesions suffer from permanently altered network function. Therefore therapeutic interventions aiming for remyelination have to consider both region- and time-dependent strategies.

  8. TRPA1 deficiency is protective in cuprizone-induced demyelination-A new target against oligodendrocyte apoptosis.

    PubMed

    Sághy, Éva; Sipos, Éva; Ács, Péter; Bölcskei, Kata; Pohóczky, Krisztina; Kemény, Ágnes; Sándor, Zoltán; Szőke, Éva; Sétáló, György; Komoly, Sámuel; Pintér, Erika

    2016-12-01

    Multiple sclerosis is a chronic inflammatory, demyelinating degenerative disease of the central nervous system. Current treatments target pathological immune responses to counteract the inflammatory processes. However, these drugs do not restrain the long-term progression of clinical disability. For this reason, new therapeutic approaches and identification of novel target molecules are needed to prevent demyelination or promote repair mechanisms. Transient Receptor Potential Ankyrin 1 (TRPA1) is a nonselective cation channel with relatively high Ca(2+) permeability. Its pathophysiological role in central nervous system disorders has not been elucidated yet. In the present study, we aimed to assess the distribution of TRPA1 in the mouse brain and reveal its regulatory role in the cuprizone-induced demyelination. This toxin-induced model, characterized by oligodendrocyte apoptosis and subsequent primary demyelination, allows us to investigate the nonimmune aspects of multiple sclerosis. We found that TRPA1 is expressed on astrocytes in the mouse central nervous system. Interestingly, TRPA1 deficiency significantly attenuated cuprizone-induced demyelination by reducing the apoptosis of mature oligodendrocytes. Our data suggest that TRPA1 regulates mitogen-activated protein kinase pathways, as well as transcription factor c-Jun and a proapoptotic Bcl-2 family member (Bak) expression resulting in enhanced oligodendrocyte apoptosis. In conclusion, we propose that TRPA1 receptors enhancing the intracellular Ca(2+) concentration modulate astrocyte functions, and influence the pro or anti-apoptotic pathways in oligodendrocytes. Inhibition of TRPA1 receptors might successfully diminish the degenerative pathology in multiple sclerosis and could be a promising therapeutic target to limit central nervous system damage in demyelinating diseases. GLIA 2016;64:2166-2180.

  9. Generating a Corpus of Mobile Forensic Images for Masquerading user Experimentation.

    PubMed

    Guido, Mark; Brooks, Marc; Grover, Justin; Katz, Eric; Ondricek, Jared; Rogers, Marcus; Sharpe, Lauren

    2016-11-01

    The Periodic Mobile Forensics (PMF) system investigates user behavior on mobile devices. It applies forensic techniques to an enterprise mobile infrastructure, utilizing an on-device agent named TractorBeam. The agent collects changed storage locations for later acquisition, reconstruction, and analysis. TractorBeam provides its data to an enterprise infrastructure that consists of a cloud-based queuing service, relational database, and analytical framework for running forensic processes. During a 3-month experiment with Purdue University, TractorBeam was utilized in a simulated operational setting across 34 users to evaluate techniques to identify masquerading users (i.e., users other than the intended device user). The research team surmises that all masqueraders are undesirable to an enterprise, even when a masquerader lacks malicious intent. The PMF system reconstructed 821 forensic images, extracted one million audit events, and accurately detected masqueraders. Evaluation revealed that developed methods reduced storage requirements 50-fold. This paper describes the PMF architecture, performance of TractorBeam throughout the protocol, and results of the masquerading user analysis.

  10. Disseminated nocardiosis masquerading as metastatic malignancy

    PubMed Central

    Arjun, Rajalakshmi; Padmanabhan, Arjun; Reddy Attunuru, Bhanu Prakash; Gupta, Prerna

    2016-01-01

    Nocardiosis is an uncommon gram-positive bacterial infection caused by aerobic actinomycetes of the genus Nocardia. It can be localized or systemic and is regarded as an opportunistic infection that is commonly seen in immunocompromised hosts. We report a case of disseminated nocardiosis caused by Nocardia cyriacigeorgica in a patient with underlying malignancy in whom the clinical presentation was highly suggestive of a metastatic disease. PMID:27578940

  11. Prinzmetals Angina Masquerading as Acute Pericarditis

    PubMed Central

    Jayaram, Ashwal Adamane; Rao, Mugula Sudhakar; Padmakumar, R

    2017-01-01

    Coronary artery spasm is an intense vasoconstriction of the coronary arteries and may be responsible for the myocardial ischemia, myocardial infarction as well as sudden deaths. Coronary angiography is generally needed to identify the cause. Coronary artery spasm is a multifactorial disease with underlying mechanism still poorly understood. Here, we present case of a 48-year-old male with no significant past history who presented with acute episodic onset chest pain. Clinical, Electrocardiography (ECG) and echocardiographic findings suggested pericarditis but a diagnostic coronary angiography revealed significant coronary vasospasm. Patient’s symptoms significantly improved with calcium channel blockers and Nitroglycerine (NTG). PMID:28273995

  12. A Bleeding Duodenal GIST Masquerading as Refractory Peptic Ulcer Disease

    PubMed Central

    Jones, Jason D.; Oh, Stephen; Clark, Clancy

    2016-01-01

    Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract; however, the occurrence of a GIST in the duodenum is rare. Our case demonstrates the importance of considering GIST in the evaluation of refractory duodenal ulcers, as well as the utilization of endoscopic ultrasound in the evaluation of these lesions. PMID:28119940

  13. Adenocarcinoma of lung masquerading as systemic auto-immune disease.

    PubMed

    Naha, Kushal; Thakare, Sayali; Vivek, G; Prabhu, Mukhyaprana

    2012-06-14

    A 40-year-old previously healthy male presented with acute onset painless dimness of vision in both eyes since the past week and low-grade fever, anorexia and weight loss for the past 1 month. He had been evaluated at a local hospital and diagnosed to have a posterior cerebral artery territory infarct on the left side on the strength of cranial CT. Shortly after receiving antiplatelets and warfarin he had developed severe coagulopathy as evidenced by haematemesis, epistaxis and haematuria. Preliminary investigation revealed prolonged clotting parameters, renal failure and anaemia. Cerebral MRI showed multiple areas of cortical haemorrhage. In the course of his hospital stay, he developed further stigmata of auto-immunity including Coomb's positive haemolytic anaemia, recurrent venous thromboses and a palpable purpuric truncal rash. He was eventually diagnosed to have an adenocarcinoma of the lung, and was subsequently referred to an oncologist for further therapy.

  14. Intraventricular injections of mesenchymal stem cells activate endogenous functional remyelination in a chronic demyelinating murine model

    PubMed Central

    Cruz-Martinez, P; González-Granero, S; Molina-Navarro, M M; Pacheco-Torres, J; García-Verdugo, J M; Geijo-Barrientos, E; Jones, J; Martinez, S

    2016-01-01

    Current treatments for demyelinating diseases are generally only capable of ameliorating the symptoms, with little to no effect in decreasing myelin loss nor promoting functional recovery. Mesenchymal stem cells (MSCs) have been shown by many researchers to be a potential therapeutic tool in treating various neurodegenerative diseases, including demyelinating disorders. However, in the majority of the cases, the effect was only observed locally, in the area surrounding the graft. Thus, in order to achieve general remyelination in various brain structures simultaneously, bone marrow-derived MSCs were transplanted into the lateral ventricles (LVs) of the cuprizone murine model. In this manner, the cells may secrete soluble factors into the cerebrospinal fluid (CSF) and boost the endogenous oligodendrogenic potential of the subventricular zone (SVZ). As a result, oligodendrocyte progenitor cells (OPCs) were recruited within the corpus callosum (CC) over time, correlating with an increased myelin content. Electrophysiological studies, together with electron microscopy (EM) analysis, indicated that the newly formed myelin correctly enveloped the demyelinated axons and increased signal transduction through the CC. Moreover, increased neural stem progenitor cell (NSPC) proliferation was observed in the SVZ, possibly due to the tropic factors released by the MSCs. In conclusion, the findings of this study revealed that intraventricular injections of MSCs is a feasible method to elicit a paracrine effect in the oligodendrogenic niche of the SVZ, which is prone to respond to the factors secreted into the CSF and therefore promoting oligodendrogenesis and functional remyelination. PMID:27171265

  15. An uncommon cause of bifacial weakness and non-length-dependent demyelinating neuropathy

    PubMed Central

    Nagappa, Madhu; Taly, Arun B.; Mahadevan, Anita; Pooja, Mailankody; Bindu, Parayil Sankaran; Chickabasaviah, Yasha T.; Gayathri, Narayanappa; Sinha, Sanjib

    2015-01-01

    Tangier disease is a rare metabolic disorder that causes neuropathy in half of the affected individuals. We present the clinical, electrophysiological, and histopathological findings in a middle-aged gentleman of Tangier disease who was initially diagnosed as leprosy and treated with antileprosy drugs. The presence of a demyelinating electrophysiology in a patient with predominant upper limb involvement and facial diplegia should raise the suspicion of Tangier disease. Estimation of serum lipids should form a part of routine evaluation in order to avoid misdiagnosis. PMID:26713019

  16. Ocular Neuromyotonia Associated with Chronic Inflammatory Demyelinating Polyneuropathy.

    PubMed

    Kung, Nathan H; Bucelli, Robert C; McClelland, Collin M; Van Stavern, Gregory P

    2015-10-01

    Ocular neuromyotonia (ONM) is a neuro-ophthalmic disorder characterized by episodic diplopia caused by contraction of one or more ocular muscles due to spontaneous excitation of the respective ocular motor nerve. We report a patient whose ocular neuromyotonia arose in the setting of a subacute demyelinating polyneuropathy consistent with chronic inflammatory demyelinating polyneuropathy (CIDP) and subsequently resolved following the initiation of intravenous immunoglobulin (IVIg) for her neuropathy. Our patient provides additional evidence towards the role of demyelination and ephaptic neurotransmission in ocular neuromyotonia and also represents the first reported case of ocular neuromyotonia associated with a systemic neurological condition.

  17. Eosinophilic mastitis masquerading as breast carcinoma

    PubMed Central

    Garg, M; Kumar, S; Neogi, S

    2012-01-01

    We report the sixth case of Eosinophilic Mastitis, presenting similarly enough to be confused with breast carcinoma. A 50 year old lady presented with a six month history of progressively enlarging asymptomatic breast lump, cough and breathlessness. Clinical examination, mammography and axillary lymphadenopathy suggested malignant disease. Ronchi were heard on chest auscultation. Needle cytology was twice inconclusive and Tru-cut biopsy showed acute on chronic inflammation. Blood investigations revealed significant peripheral eosinophilia. Open biopsy reported eosinophilic mastits, correlating with peripheral eosinophilia and pulmonary symptoms. The patient responded to conservative management. Eosinophilic infiltration of the breast is a rare manifestation of tissue involvement in peripheral eosinophilia. Asthma, Churgh-Strauss Syndrome and hyper-eosinophilic syndromes are associated. Importantly, if a clinically and radiologically malignant breast lump in asthmatic ladies with peripheral eosinophilia is not confirmed on cytology, this entity could be a diagnosis, potentially saving the patient from surgery. PMID:24960670

  18. Eosinophilic mastitis masquerading as breast carcinoma.

    PubMed

    Garg, M; Kumar, S; Neogi, S

    2012-06-01

    We report the sixth case of Eosinophilic Mastitis, presenting similarly enough to be confused with breast carcinoma. A 50 year old lady presented with a six month history of progressively enlarging asymptomatic breast lump, cough and breathlessness. Clinical examination, mammography and axillary lymphadenopathy suggested malignant disease. Ronchi were heard on chest auscultation. Needle cytology was twice inconclusive and Tru-cut biopsy showed acute on chronic inflammation. Blood investigations revealed significant peripheral eosinophilia. Open biopsy reported eosinophilic mastits, correlating with peripheral eosinophilia and pulmonary symptoms. The patient responded to conservative management. Eosinophilic infiltration of the breast is a rare manifestation of tissue involvement in peripheral eosinophilia. Asthma, Churgh-Strauss Syndrome and hyper-eosinophilic syndromes are associated. Importantly, if a clinically and radiologically malignant breast lump in asthmatic ladies with peripheral eosinophilia is not confirmed on cytology, this entity could be a diagnosis, potentially saving the patient from surgery.

  19. Pinworm infection masquerading as colorectal liver metastasis

    PubMed Central

    Roberts, KJ; Hubscher, S; Mangat, K; Sutcliffe, R; Marudanayagam, R

    2012-01-01

    Enterobius vermicularis is responsible for a variety of diseases but rarely affects the liver. Accurate characterisation of suspected liver metastases is essential to avoid unnecessary surgery. In the presented case, following a diagnosis of rectal cancer, a solitary liver nodule was diagnosed as a liver metastasis due to typical radiological features and subsequently resected. At pathological assessment, however, a necrotic nodule containing E vermicularis was identified. Solitary necrotic nodules of the liver are usually benign but misdiagnosed frequently as malignant due to radiological features. It is standard practice to diagnose colorectal liver metastases solely on radiological evidence. Without obtaining tissue prior to liver resection, misdiagnosis of solitary necrotic nodules of the liver will continue to occur. PMID:22943320

  20. Ophthalmic masquerades of the atherosclerotic carotids

    PubMed Central

    Arthur, Anupriya; Alexander, Anika; Bal, Simerpreet; Sivadasan, Ajith; Aaron, Sanjith

    2014-01-01

    Patients with carotid atherosclerosis can present with ophthalmic symptoms. These symptoms and signs can be due to retinal emboli, hypoperfusion of the retina and choroid, opening up of collateral channels, or chronic hypoperfusion of the globe (ocular ischemic syndrome). These pathological mechanisms can produce many interesting signs and a careful history can bring out important past symptoms pointing toward the carotid as the source of the patient's presenting symptom. Such patients are at high risk for an ischemic stroke, especially in the subsequent few days following their first acute symptom. It is important for clinicians to be familiar with these ophthalmic symptoms and signs caused by carotid atherosclerosis for making an early diagnosis and to take appropriate measures to prevent a stroke. This review elaborates the clinical features, importance, and implications of various ophthalmic symptoms and signs resulting from atherosclerotic carotid artery disease. PMID:24817748

  1. Acute paretic syndrome in juvenile White Leghorn chickens resembles late stages of acute inflammatory demyelinating polyneuropathies in humans

    PubMed Central

    2010-01-01

    Background Sudden limb paresis is a common problem in White Leghorn flocks, affecting about 1% of the chicken population before achievement of sexual maturity. Previously, a similar clinical syndrome has been reported as being caused by inflammatory demyelination of peripheral nerve fibres. Here, we investigated in detail the immunopathology of this paretic syndrome and its possible resemblance to human neuropathies. Methods Neurologically affected chickens and control animals from one single flock underwent clinical and neuropathological examination. Peripheral nervous system (PNS) alterations were characterised using standard morphological techniques, including nerve fibre teasing and transmission electron microscopy. Infiltrating cells were phenotyped immunohistologically and quantified by flow cytometry. The cytokine expression pattern was assessed by quantitative real-time PCR (qRT-PCR). These investigations were accomplished by MHC genotyping and a PCR screen for Marek's disease virus (MDV). Results Spontaneous paresis of White Leghorns is caused by cell-mediated, inflammatory demyelination affecting multiple cranial and spinal nerves and nerve roots with a proximodistal tapering. Clinical manifestation coincides with the employment of humoral immune mechanisms, enrolling plasma cell recruitment, deposition of myelin-bound IgG and antibody-dependent macrophageal myelin-stripping. Disease development was significantly linked to a 539 bp microsatellite in MHC locus LEI0258. An aetiological role for MDV was excluded. Conclusions The paretic phase of avian inflammatory demyelinating polyradiculoneuritis immunobiologically resembles the late-acute disease stages of human acute inflammatory demyelinating polyneuropathy, and is characterised by a Th1-to-Th2 shift. PMID:20109187

  2. Central canal ependymal cells proliferate extensively in response to traumatic spinal cord injury but not demyelinating lesions.

    PubMed

    Lacroix, Steve; Hamilton, Laura K; Vaugeois, Alexandre; Beaudoin, Stéfanny; Breault-Dugas, Christian; Pineau, Isabelle; Lévesque, Sébastien A; Grégoire, Catherine-Alexandra; Fernandes, Karl J L

    2014-01-01

    The adult mammalian spinal cord has limited regenerative capacity in settings such as spinal cord injury (SCI) and multiple sclerosis (MS). Recent studies have revealed that ependymal cells lining the central canal possess latent neural stem cell potential, undergoing proliferation and multi-lineage differentiation following experimental SCI. To determine whether reactive ependymal cells are a realistic endogenous cell population to target in order to promote spinal cord repair, we assessed the spatiotemporal dynamics of ependymal cell proliferation for up to 35 days in three models of spinal pathologies: contusion SCI using the Infinite Horizon impactor, focal demyelination by intraspinal injection of lysophosphatidylcholine (LPC), and autoimmune-mediated multi-focal demyelination using the active experimental autoimmune encephalomyelitis (EAE) model of MS. Contusion SCI at the T9-10 thoracic level stimulated a robust, long-lasting and long-distance wave of ependymal proliferation that peaked at 3 days in the lesion segment, 14 days in the rostral segment, and was still detectable at the cervical level, where it peaked at 21 days. This proliferative wave was suppressed distal to the contusion. Unlike SCI, neither chemical- nor autoimmune-mediated demyelination triggered ependymal cell proliferation at any time point, despite the occurrence of demyelination (LPC and EAE), remyelination (LPC) and significant locomotor defects (EAE). Thus, traumatic SCI induces widespread and enduring activation of reactive ependymal cells, identifying them as a robust cell population to target for therapeutic manipulation after contusion; conversely, neither demyelination, remyelination nor autoimmunity appears sufficient to trigger proliferation of quiescent ependymal cells in models of MS-like demyelinating diseases.

  3. Lacrimal and nasal masquerades of congenital nasolacrimal duct obstructions: etiology, management, and outcomes.

    PubMed

    Kamal, Saurabh; Ali, Mohammad Javed; Gupta, Adit; Naik, Milind N

    2015-12-01

    The purpose of this study was to report various conditions masquerading as congenital nasolacrimal duct obstruction (CNLDO). Retrospective review was designed in a tertiary hospital setting. 92 eyes of 65 consecutive patients were included in this study. All patients presenting with CNLDO symptomatology but where the diagnosis of CNLDO was subsequently ruled out were included in the study. The study patients were recruited from a single surgeon's (MJA) tertiary eye care practice over a 3-year period from 2011 to 2013. A detailed clinical evaluation and a further lacrimal system evaluation were performed under general anesthesia. The main outcome measure was other lacrimal and nasal conditions masquerading as CNLDO. Average age at presentation was 43.49 ± 31.78 months. All cases had symptoms of either watering or discharge with an increase tear meniscus or abnormal fluorescein dye disappearance test. The commonest masquerades of congenital nasolacrimal duct obstruction include incomplete punctal canalisation (27.2 %), functional epiphora (14.1 %), punctal agenesis (14.1 %), monocanalicular obstructions (10.8 %), and presaccal stenosis (8.7 %). Each masquerade was managed specifically and at the last follow-up of 5.85 ± 10.85 months, 63 % eyes (58/92) had no epiphora and 2.2 % (2/92) eyes had occasional epiphora. Parents of patients with punctal agenesis were counseled for option of conjunctivodacryocystorhinostomy in future. Incomplete punctal canalisation is the commonest masquerade among many conditions that may mimic CNLDO and mandates a careful evaluation. Specific management of each masquerade results in satisfactory outcomes.

  4. [Jawbone metastasis masquerading as dental pain].

    PubMed

    Goldman, Y; Yarom, N

    2016-01-01

    Metastases to the oral cavity are rare. However, in 25% of cases, oral symptoms will be the first sign of metastatic disease. The incidence of jaws metastases is twice as high as the incidence of metastases to the soft tissues of the oral cavity. In some cases, jaws metastases can mimic dental or periodontal pain. We report a case of a 67 year old female who was referred to our clinic because of severe pain on her left posterior mandible which was not relieved by endodontic treatment of the first and second molar. She was diagnosed with breast cancer in 2005 and had been treated with surgery, chemotherapy and radiotherapy. Seven years later, lung metastases were found and she was treated with chemotherapy. Later on, brain metastases developed which had been treated with radiotherapy. On presentation, she complained of pain on the posterior left mandible which was accompanied by a burning sensation of the lower left lip and chin. CT scan revealed a soft tissue mass perforating the lingual and buccal plates of the posterior left mandible, which was compatible with a diagnosis of metastasis. Radiotherapy rapidly relieved the pain. Unfortunately, the patient passed away one month later. Dentists should be able to recognize the signs and symptoms associated with metastases to the jaws and should include it in the differential diagnosis, especially in patients with oncologic background.

  5. Rare adipose disorders (RADs) masquerading as obesity

    PubMed Central

    Herbst, Karen L

    2012-01-01

    Rare adipose disorders (RADs) including multiple symmetric lipomatosis (MSL), lipedema and Dercum's disease (DD) may be misdiagnosed as obesity. Lifestyle changes, such as reduced caloric intake and increased physical activity are standard care for obesity. Although lifestyle changes and bariatric surgery work effectively for the obesity component of RADs, these treatments do not routinely reduce the abnormal subcutaneous adipose tissue (SAT) of RADs. RAD SAT likely results from the growth of a brown stem cell population with secondary lymphatic dysfunction in MSL, or by primary vascular and lymphatic dysfunction in lipedema and DD. People with RADs do not lose SAT from caloric limitation and increased energy expenditure alone. In order to improve recognition of RADs apart from obesity, the diagnostic criteria, histology and pathophysiology of RADs are presented and contrasted to familial partial lipodystrophies, acquired partial lipodystrophies and obesity with which they may be confused. Treatment recommendations focus on evidence-based data and include lymphatic decongestive therapy, medications and supplements that support loss of RAD SAT. Associated RAD conditions including depression, anxiety and pain will improve as healthcare providers learn to identify and adopt alternative treatment regimens for the abnormal SAT component of RADs. Effective dietary and exercise regimens are needed in RAD populations to improve quality of life and construct advanced treatment regimens for future generations. PMID:22301856

  6. Chronic inflammatory demyelinating polyradiculoneuropathy: from pathology to phenotype

    PubMed Central

    Mathey, Emily K; Park, Susanna B; Hughes, Richard A C; Pollard, John D; Armati, Patricia J; Barnett, Michael H; Taylor, Bruce V; Dyck, P James B; Kiernan, Matthew C; Lin, Cindy S-Y

    2015-01-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an inflammatory neuropathy, classically characterised by a slowly progressive onset and symmetrical, sensorimotor involvement. However, there are many phenotypic variants, suggesting that CIDP may not be a discrete disease entity but rather a spectrum of related conditions. While the abiding theory of CIDP pathogenesis is that cell-mediated and humoral mechanisms act together in an aberrant immune response to cause damage to peripheral nerves, the relative contributions of T cell and autoantibody responses remain largely undefined. In animal models of spontaneous inflammatory neuropathy, T cell responses to defined myelin antigens are responsible. In other human inflammatory neuropathies, there is evidence of antibody responses to Schwann cell, compact myelin or nodal antigens. In this review, the roles of the cellular and humoral immune systems in the pathogenesis of CIDP will be discussed. In time, it is anticipated that delineation of clinical phenotypes and the underlying disease mechanisms might help guide diagnostic and individualised treatment strategies for CIDP. PMID:25677463

  7. Astrocytes Are an Early Target in Osmotic Demyelination Syndrome

    PubMed Central

    Nicaise, Charles; Soupart, Alain; Boom, Alain; Schiettecatte, Johan; Pochet, Roland; Brion, Jean Pierre

    2011-01-01

    Abrupt osmotic changes during rapid correction of chronic hyponatremia result in demyelinative brain lesions, but the sequence of events linking rapid osmotic changes to myelin loss is not yet understood. Here, in a rat model of osmotic demyelination syndrome, we found that massive astrocyte death occurred after rapid correction of hyponatremia, delineating the regions of future myelin loss. Astrocyte death caused a disruption of the astrocyte-oligodendrocyte network, rapidly upregulated inflammatory cytokines genes, and increased serum S100B, which predicted clinical manifestations and outcome of osmotic demyelination. These results support a model for the pathophysiology of osmotic brain injury in which rapid correction of hyponatremia triggers apoptosis in astrocytes followed by a loss of trophic communication between astrocytes and oligodendrocytes, secondary inflammation, microglial activation, and finally demyelination. PMID:21885671

  8. Chronic Inflammatory Demyelinating Polyradiculoneuropathy: From Bench to Bedside

    PubMed Central

    Peltier, Amanda C.; Donofrio, Peter D.

    2015-01-01

    Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) is the most common treatable chronic autoimmune neuropathy. Multiple diagnostic criteria have been established, with the primary goal of identifying neurophysiologic hallmarks of acquired demyelination. Treatment modalities have expanded to include numerous immuno-modulatory therapies, although the best evidence continues to be for corticosteroids, plasma exchange, and intravenous immunoglobulins (IVIg). This review describes the pathology, epidemiology, pathogenesis, diagnosis, and treatment of CIDP. PMID:23117943

  9. Chronic inflammatory demyelinating polyradiculoneuropathy: from bench to bedside.

    PubMed

    Peltier, Amanda C; Donofrio, Peter D

    2012-07-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is the most common treatable chronic autoimmune neuropathy. Multiple diagnostic criteria have been established, with the primary goal of identifying neurophysiologic hallmarks of acquired demyelination. Treatment modalities have expanded to include numerous immunomodulatory therapies, although the best evidence continues to be for corticosteroids, plasma exchange, and intravenous immunoglobulin (IVIg). This review describes the pathology, epidemiology, pathogenesis, diagnosis, and treatment of CIDP.

  10. White matter changes in paediatric multiple sclerosis and monophasic demyelinating disorders.

    PubMed

    Longoni, Giulia; Brown, Robert A; MomayyezSiahkal, Parya; Elliott, Colm; Narayanan, Sridar; Bar-Or, Amit; Ann Marrie, Ruth; Ann Yeh, E; Filippi, Massimo; Banwell, Brenda; Arnold, Douglas L

    2017-03-14

    Most children who experience an acquired demyelinating syndrome of the central nervous system will have a monophasic disease course, with no further clinical or radiological symptoms. A subset will be diagnosed with multiple sclerosis, a life-long disorder. Using linear mixed effects models we examined longitudinal diffusion properties of normal-appearing white matter in 505 serial scans of 132 paediatric participants with acquired demyelinating syndromes followed for a median of 4.4 years, many from first clinical presentation, and 106 scans of 80 healthy paediatric participants. Fifty-three participants with demyelinating syndromes eventually received a diagnosis of paediatric-onset multiple sclerosis. Diffusion tensor imaging measures properties of water diffusion through tissue, which normally becomes increasingly restricted and anisotropic in the brain during childhood and adolescence, as fibre bundles develop and myelinate. In the healthy paediatric participants, our data demonstrate the expected trajectory of more restricted and anisotropic white matter diffusivity with increasing age. However, in participants with multiple sclerosis, fractional anisotropy decreased and mean diffusivity of non-lesional, normal-appearing white matter progressively increased after clinical presentation, suggesting not only a failure of age-expected white matter development but also a progressive loss of tissue integrity. Surprisingly, patients with monophasic disease failed to show age-expected changes in diffusion parameters in normal-appearing white matter, although they did not show progressive loss of integrity over time. Further analysis demonstrated that participants with monophasic disease experienced different post-onset trajectories in normal-appearing white matter depending on their presenting phenotype: those with acute disseminated encephalomyelitis demonstrated abnormal trajectories of diffusion parameters compared to healthy paediatric participants, as did

  11. Occurrence and long-term outcome of tumefactive demyelinating lesions in multiple sclerosis.

    PubMed

    Totaro, Rocco; Di Carmine, C; Splendiani, A; Torlone, S; Patriarca, L; Carrocci, C; Sciamanna, S; Marini, C; Carolei, A

    2016-07-01

    Although tumefactive multiple sclerosis is a well recognized variant of multiple sclerosis, prognostic uncertainty still exists about long term prognosis. The aim of this study was to estimate the occurrence and long term outcome of tumefactive demyelinating lesions (TDLs) in a cohort of multiple sclerosis patients. We reviewed brain MRI of 443 patients referred to our MS clinic. All patients meeting the McDonald criteria for multiple sclerosis and showing at least one TDL were included. Kaplan-Meier estimates of disease-free survival in patient cohort were compared with control group without TDLs using a log-rank test. Seven cases with TDLs were identified (occurrence 1.58 %). Tumefactive demyelinating lesion recurrence was 16.6 %. Cumulative proportion of patients free from clinical relapse and from new T2 lesions was lower in the control group although not reaching statistical significance (30 vs 50 %; P = 0.666 and 21.7 vs 33.3 %; P = 0.761, respectively). Disability progression analysis showed a not significant trend towards lower probability of remaining progression free for TDL patients (50 vs 61 %; P = 0.295). Occurrence of tumefactive demyelinating lesions in our cohort was higher than those reported in other studies. Overall, TDLs were not predictive of poor outcome in terms of disability progression.

  12. Astrocyte-derived tissue Transglutaminase affects fibronectin deposition, but not aggregation, during cuprizone-induced demyelination

    PubMed Central

    Espitia Pinzon, Nathaly; Sanz-Morello, Berta; Brevé, John J. P.; Bol, John G. J. M.; Drukarch, Benjamin; Bauer, Jan; Baron, Wia; van Dam, Anne-Marie

    2017-01-01

    Astrogliosis as seen in Multiple Sclerosis (MS) develops into astroglial scarring, which is beneficial because it seals off the site of central nervous system (CNS) damage. However, astroglial scarring also forms an obstacle that inhibits axon outgrowth and (re)myelination in brain lesions. This is possibly an important cause for incomplete remyelination in the CNS of early stage MS patients and for failure in remyelination when the disease progresses. In this study we address whether under demyelinating conditions in vivo, tissue Transglutaminase (TG2), a Ca2+ -dependent enzyme that catalyses posttranslational modification of proteins, contributes to extracellular matrix (ECM) deposition and/or aggregation. We used the cuprizone model for de- and remyelination. TG2 immunoreactivity and enzymatic activity time-dependently appeared in astrocytes and ECM, respectively, in the corpus callosum of cuprizone-treated mice. Enhanced presence of soluble monomeric and multimeric fibronectin was detected during demyelination, and fibronectin immunoreactivity was slightly decreased in cuprizone-treated TG2−/− mice. In vitro TG2 overexpression in astrocytes coincided with more, while knock-down of TG2 with less fibronectin production. TG2 contributes, at least partly, to fibronectin production, and may play a role in fibronectin deposition during cuprizone-induced demyelination. Our observations are of interest in understanding the functional implications of TG2 during astrogliosis. PMID:28128219

  13. Selective inhibitors of nuclear export avert progression in preclinical models of inflammatory demyelination

    PubMed Central

    Haines, Jeffery D.; Herbin, Olivier; de la Hera, Belén; Vidaurre, Oscar G.; Moy, Gregory A.; Sun, Qingxiang; Fung, Ho Yee Joyce; Albrecht, Stephanie; Alexandropoulos, Konstantina; McCauley, Dilara; Chook, Yuh Min; Kuhlmann, Tanja; Kidd, Grahame J.; Shacham, Sharon; Casaccia, Patrizia

    2015-01-01

    Axonal damage has been associated with aberrant protein trafficking. This study characterizes a novel class of compounds targeting nucleo-cytoplasmic shuttling, by binding to the catalytic groove of the nuclear export protein XPO1/CRM1 (chromosome region maintenance protein1). Oral administration of novel reversible CRM1 inhibitors in preclinical murine models of demyelination significantly attenuated disease progression, even when started after the onset of paralysis. Clinical efficacy was associated with decreased proliferation of immune cells, characterized by nuclear accumulation of cell cycle inhibitors, and preservation of cytoskeletal integrity even in demyelinated axons. Neuroprotection was not limited to models of demyelination, but observed also in other mouse models of axonal damage (i.e. kainic acid injection) and detected in cultured neurons after knockdown of Xpo1, the gene encoding for CRM1. A proteomic screen for target molecules revealed that CRM1 inhibitors in neurons prevented nuclear export of molecules associated with axonal damage while retaining transcription factors modulating neuroprotection. PMID:25706475

  14. Tamoxifen accelerates the repair of demyelinated lesions in the central nervous system

    PubMed Central

    Gonzalez, Ginez A.; Hofer, Matthias P.; Syed, Yasir A.; Amaral, Ana I.; Rundle, Jon; Rahman, Saifur; Zhao, Chao; Kotter, Mark R. N.

    2016-01-01

    Enhancing central nervous system (CNS) myelin regeneration is recognized as an important strategy to ameliorate the devastating consequences of demyelinating diseases such as multiple sclerosis. Previous findings have indicated that myelin proteins, which accumulate following demyelination, inhibit remyelination by blocking the differentiation of rat oligodendrocyte progenitor cells (OPCs) via modulation of PKCα. We therefore screened drugs for their potential to overcome this differentiation block. From our screening, tamoxifen emerges as a potent inducer of OPC differentiation in vitro. We show that the effects of tamoxifen rely on modulation of the estrogen receptors ERα, ERβ, and GPR30. Furthermore, we demonstrate that administration of tamoxifen to demyelinated rats in vivo accelerates remyelination. Tamoxifen is a well-established drug and is thus a promising candidate for a drug to regenerate myelin, as it will not require extensive safety testing. In addition, Tamoxifen plays an important role in biomedical research as an activator of inducible genetic models. Our results highlight the importance of appropriate controls when using such models. PMID:27554391

  15. A Unified Frequency Domain Model to Study the Effect of Demyelination on Axonal Conduction

    PubMed Central

    Chaubey, Saurabh; Goodwin, Shikha J.

    2016-01-01

    Multiple sclerosis is a disease caused by demyelination of nerve fibers. In order to determine the loss of signal with the percentage of demyelination, we need to develop models that can simulate this effect. Existing time-based models does not provide a method to determine the influences of demyelination based on simulation results. Our goal is to develop a system identification approach to generate a transfer function in the frequency domain. The idea is to create a unified modeling approach for neural action potential propagation along the length of an axon containing number of Nodes of Ranvier (N). A system identification approach has been used to identify a transfer function of the classical Hodgkin–Huxley equations for membrane voltage potential. Using this approach, we model cable properties and signal propagation along the length of the axon with N node myelination. MATLAB/Simulink platform is used to analyze an N node-myelinated neuronal axon. The ability to transfer function in the frequency domain will help reduce effort and will give a much more realistic feel when compared to the classical time-based approach. Once a transfer function is identified, the conduction as a cascade of each linear time invariant system-based transfer function can be modeled. Using this approach, future studies can model the loss of myelin in various parts of nervous system. PMID:27103847

  16. A Unified Frequency Domain Model to Study the Effect of Demyelination on Axonal Conduction.

    PubMed

    Chaubey, Saurabh; Goodwin, Shikha J

    2016-01-01

    Multiple sclerosis is a disease caused by demyelination of nerve fibers. In order to determine the loss of signal with the percentage of demyelination, we need to develop models that can simulate this effect. Existing time-based models does not provide a method to determine the influences of demyelination based on simulation results. Our goal is to develop a system identification approach to generate a transfer function in the frequency domain. The idea is to create a unified modeling approach for neural action potential propagation along the length of an axon containing number of Nodes of Ranvier (N). A system identification approach has been used to identify a transfer function of the classical Hodgkin-Huxley equations for membrane voltage potential. Using this approach, we model cable properties and signal propagation along the length of the axon with N node myelination. MATLAB/Simulink platform is used to analyze an N node-myelinated neuronal axon. The ability to transfer function in the frequency domain will help reduce effort and will give a much more realistic feel when compared to the classical time-based approach. Once a transfer function is identified, the conduction as a cascade of each linear time invariant system-based transfer function can be modeled. Using this approach, future studies can model the loss of myelin in various parts of nervous system.

  17. Cellular sources and targets of IFN-γ-mediated protection against viral demyelination and neurological deficits

    PubMed Central

    Murray, Paul D.; McGavern, Dorian B.; Pease, Larry R.; Rodriguez, Moses

    2017-01-01

    IFN-γ is an anti-viral and immunomodulatory cytokine critical for resistance to multiple pathogens. Using mice with targeted disruption of the gene for IFN-γ, we previously demonstrated that this cytokine is critical for resistance to viral persistence and demyelination in the Theiler’s virus model of multiple sclerosis. During viral infections, IFN-γ is produced by natural killer (NK) cells, CD4+ and CD8+ T cells; however, the proportions of lymphocyte subsets responding to virus infection influences the contributions to IFN-γ-mediated protection. To determine the lymphocyte subsets that produce IFN-γ to maintain resistance, we used adoptive transfer strategies to generate mice with lymphocyte-specific deficiencies in IFN-γ-production. We demonstrate that IFN-γ production by both CD4+ and CD8+ T cell subsets is critical for resistance to Theiler’s murine encephalomyelitis virus (TMEV)-induced demyelination and neurological disease, and that CD4+ T cells make a greater contribution to IFN-γ-mediated protection. To determine the cellular targets of IFN-γ-mediated responses, we used adoptive transfer studies and bone marrow chimerism to generate mice in which either hematopoietic or somatic cells lacked the ability to express IFN-γ receptor. We demonstrate that IFN-γ receptor must be present on central nervous system glia, but not bone marrow-derived lymphocytes, in order to maintain resistance to TMEV-induced demyelination. PMID:11857334

  18. Up-regulation of the hyaluronate receptor CD44 in canine distemper demyelinated plaques.

    PubMed

    Alldinger, S; Fonfara, S; Kremmer, E; Baumgärtner, W

    2000-02-01

    CD44 antigen (CD44), the principle cell surface receptor for hyaluronate, is up-regulated in the human demyelinating disease multiple sclerosis on fibrous astrocytes. As astrocytes are the main target cell of canine distemper virus (CDV), the consequences of a CDV infection on the CD44 expression and distribution in brains with spontaneous demyelinating canine distemper encephalitis (CDE) were of interest. Thirteen acute, 35 subacute, and 11 chronic plaques of nine dogs with immunohistologically confirmed CDE and brains of control dogs were included in the study. For light microscopy, 5-micron-thick serial sections were stained with H&E and incubated with monoclonal antibodies (mAbs) against CD44 and canine distemper virus nucleoprotein and polyclonal antibodies (pAbs) against glial fibrillary acidic protein (GFAP) and myelin basic protein (MBP). For immunoelectron microscopy, 90-nm-thick sections were double stained with anti-GFAP and anti-CD44 mAbs to specify CD44-expressing structures. In controls, CD44 was diffusely distributed in the white matter and single meningeal cells exhibited a marginal expression of the antigen. In acute and more prominently in subacute demyelinating encephalitis, there was a plaque-associated up-regulation of CD44 which paralleled GFAP. In chronic demyelinating lesions, a reduction of CD44 associated with a loss of GFAP-positive astrocytes was noted. Additionally, in chronic plaques, CD44 was expressed on the cell membrane of perivascular mononuclear cells. Immunoelectron microscopically, in controls, CD44 was rarely demonstrated on astrocytic cell processes. In contrast, in brains with CDE CD44 was found on the cell membrane of broadened astrocytic cell processes. In summary, CD44 is up-regulated on astrocytes in the early phase of CDE and seems to represent a marker for the activation of immune cells in the late phase of the infection.

  19. Acceleration in the rate of CNS remyelination in lysolecithin-induced demyelination.

    PubMed

    Pavelko, K D; van Engelen, B G; Rodriguez, M

    1998-04-01

    One important therapeutic goal during CNS injury from trauma or demyelinating diseases such as multiple sclerosis is to develop methods to promote remyelination. We tested the hypothesis that spontaneous remyelination in the toxic nonimmune model of lysolecithin-induced demyelination can be enhanced by manipulating the inflammatory response. In PBS-treated SJL/J mice, the number of remyelinating axons per square millimeter of lesion area increased significantly 3 and 5 weeks after lysolecithin injection in the spinal cord. However, methylprednisolone or a monoclonal antibody (mAb), SCH94.03, developed for its ability to promote remyelination in the Theiler's virus murine model of demyelination, further increased the number of remyelinating axons per lesion area at 3 weeks by a factor of 2.6 and 1.9, respectively, but did not increase the ratio of myelin sheath thickness to axon diameter or the number of cells incorporating tritiated thymidine in the lesion. After 3 weeks, the number of remyelinating axons in the methylprednisolone or mAb SCH94.03 treatment groups was similar to the spontaneous remyelination in the 5 week PBS control-treated group, indicating that these treatments promoted remyelination by increasing its rate rather than its extent. To address a mechanism for promoting remyelination, through an effect on scavenger function, we assessed morphometrically the number of macrophages in lesions after methylprednisolone and mAb SCH94.03 treatment. Methylprednisolone reduced the number of macrophages, but SCH94.03 did not, although both enhanced remyelination. This study supports the hypothesis that even in toxic nonprimary immune demyelination, manipulating the inflammatory response is a benefit in myelin repair.

  20. Thyroid hormone alleviates demyelination induced by cuprizone through its role in remyelination during the remission period.

    PubMed

    Zhang, Mao; Zhan, Xiao L; Ma, Zi Y; Chen, Xing S; Cai, Qi Y; Yao, Zhong X

    2015-09-01

    Multiple sclerosis (MS) is a disease induced by demyelination in the central nervous system, and the remission period of MS is crucial for remyelination. In addition, abnormal levels of thyroid hormone (TH) have been identified in MS. However, in the clinic, insufficient attention has been paid to the role of TH in the remission period. Indeed, TH not only functions in the development of the brain but also affects myelination. Therefore, it is necessary to observe the effect of TH on remyelination during this period. A model of demyelination induced by cuprizone (CPZ) was used to observe the function of TH in remyelination during the remission period of MS. Through weighing and behavioral tests, we found that TH improved the physical symptoms of mice impaired by CPZ. Supplementation of TH led to the repair of myelin as detected by immunohistochemistry and western blot. In addition, a sufficient TH supply resulted in an increase in myelinated axons without affecting myelin thickness and g ratio in the corpus callosum, as detected by electron microscopy. Double immunostaining with myelin basic protein and neurofilament 200 (NF200) showed that the CPZ-induced impairment of axons was alleviated by TH. Conversely, insufficient TH induced by 6-propyl-2-thiouracil resulted in the enlargement of mitochondria. Furthermore, we found that an adequate supply of TH promoted the proliferation and differentiation of oligodendrocyte lineage cells by immunofluorescence, which was beneficial to remyelination. Further, we found that TH reduced the number of astrocytes without affecting microglia. Conclusively, it was shown that TH alleviated demyelination induced by CPZ by promoting the development of oligodendrocyte lineage cells and remyelination. The critical time for remyelination is the remission period of MS. TH plays a significant role in alleviating demyelination during the remission period in the clinical treatment of MS.

  1. HCV-related central and peripheral nervous system demyelinating disorders.

    PubMed

    Mariotto, Sara; Ferrari, Sergio; Monaco, Salvatore

    2014-01-01

    Chronic infection with hepatitis C virus (HCV) is associated with a large spectrum of extrahepatic manifestations (EHMs), mostly immunologic/rheumatologic in nature owing to B-cell proliferation and clonal expansion. Neurological complications are thought to be immune-mediated or secondary to invasion of neural tissues by HCV, as postulated in transverse myelitis and encephalopathic forms. Primarily axonal neuropathies, including sensorimotor polyneuropathy, large or small fiber sensory neuropathy, motor polyneuropathy, mononeuritis, mononeuritis multiplex, or overlapping syndrome, represent the most common neurological complications of chronic HCV infection. In addition, a number of peripheral demyelinating disorders are encountered, such as chronic inflammatory demyelinating polyneuropathy, the Lewis-Sumner syndrome, and cryoglobulin-associated polyneuropathy with demyelinating features. The spectrum of demyelinating forms also includes rare cases of iatrogenic central and peripheral nervous system disorders, occurring during treatment with pegylated interferon. Herein, we review HCV-related demyelinating conditions, and disclose the novel observation on the significantly increased frequency of chronic demyelinating neuropathy with anti-myelin-associated glycoprotein antibodies in a cohort of 59 consecutive patients recruited at our institution. We also report a second case of neuromyelitis optica with serum IgG autoantibody against the water channel aquaporin-4. The prompt recognition of these atypical and underestimated complications of HCV infection is of crucial importance in deciding which treatment option a patient should be offered.

  2. HCV-Related Central and Peripheral Nervous System Demyelinating Disorders

    PubMed Central

    Mariotto, Sara; Ferrari, Sergio; Monaco, Salvatore

    2014-01-01

    Chronic infection with hepatitis C virus (HCV) is associated with a large spectrum of extrahepatic manifestations (EHMs), mostly immunologic/rheumatologic in nature owing to B-cell proliferation and clonal expansion. Neurological complications are thought to be immune-mediated or secondary to invasion of neural tissues by HCV, as postulated in transverse myelitis and encephalopathic forms. Primarily axonal neuropathies, including sensorimotor polyneuropathy, large or small fiber sensory neuropathy, motor polyneuropathy, mononeuritis, mononeuritis multiplex, or overlapping syndrome, represent the most common neurological complications of chronic HCV infection. In addition, a number of peripheral demyelinating disorders are encountered, such as chronic inflammatory demyelinating polyneuropathy, the Lewis-Sumner syndrome, and cryoglobulin-associated polyneuropathy with demyelinating features. The spectrum of demyelinating forms also includes rare cases of iatrogenic central and peripheral nervous system disorders, occurring during treatment with pegylated interferon. Herein, we review HCV-related demyelinating conditions, and disclose the novel observation on the significantly increased frequency of chronic demyelinating neuropathy with anti-myelin-associated glycoprotein antibodies in a cohort of 59 consecutive patients recruited at our institution. We also report a second case of neuromyelitis optica with serum IgG autoantibody against the water channel aquaporin-4. The prompt recognition of these atypical and underestimated complications of HCV infection is of crucial importance in deciding which treatment option a patient should be offered. PMID:25198705

  3. Characterization of a new rat model for chronic inflammatory demyelinating polyneuropathies.

    PubMed

    Brun, Susana; Beaino, Wissam; Kremer, Laurent; Taleb, Omar; Mensah-Nyagan, Ayikoe Guy; Lam, Chanh D; Greer, Judith M; de Seze, Jérôme; Trifilieff, Elisabeth

    2015-01-15

    Our objective was to develop a chronic model of EAN which could be used as a tool to test treatment strategies for CIDP. Lewis rats injected with S-palmitoylated P0(180-199) peptide developed a chronic, sometimes relapsing-remitting type of disease. Our model fulfills electrophysiological criteria of demyelination with axonal degeneration, confirmed by immunohistopathology. The late phase of the chronic disease was characterized by accumulation of IL-17(+) cells and macrophages in sciatic nerves and by high serum IL-17 levels. In conclusion, we have developed a reliable and reproducible animal model resembling CIDP that can now be used for translational drug studies.

  4. Movement disorders and the osmotic demyelination syndrome.

    PubMed

    de Souza, Aaron

    2013-08-01

    With the advent of MRI, osmotic demyelination syndromes (ODS) are increasingly recognised to affect varied sites in the brain in addition to the classical central pontine lesion. Striatal involvement is seen in a large proportion of cases and results in a wide variety of movement disorders. Movement disorders and cognitive problems resulting from ODS affecting the basal ganglia may occur early in the course of the illness, or may present as delayed manifestations after the patient survives the acute phase. Such delayed symptoms may evolve over time, and may even progress despite treatment. Improved survival of patients in the last few decades due to better intensive care has led to an increase in the incidence of such delayed manifestations of ODS. While the outcome of ODS is not as dismal as hitherto believed - with the acute akinetic-rigid syndrome associated with striatal myelinolysis often responding to dopaminergic therapy - the delayed symptoms often prove refractory to medical therapy. This article presents a review of the epidemiology, pathophysiology, clinical features, imaging, and therapy of movement disorders associated with involvement of the basal ganglia in ODS. A comprehensive review of 54 previously published cases of movement disorders due to ODS, and a video recording depicting the spectrum of delayed movement disorders seen after recovery from ODS are also presented.

  5. Rare Anterior Segment Retinoblastoma Masquerading as Corneal Endotheliitis.

    PubMed

    Kelly, Alla; Kaufman, Stephen C; Ali, Rasha; Grajewski, Alana; Anderson, Jill

    2016-01-01

    We present a unique case involving a 6-year-old female with a unilateral corneal endotheliitis-like finding, who was ultimately found to have a form of anterior diffuse infiltrating retinoblastoma with no evidence of retinal involvement. The patient's presumed endotheliitis was initially treated with topical dexamethasone and oral acyclovir without improvement. She then underwent multiple fine-needle aspirations of anterior chamber fluid, which were negative for abnormal findings of viral polymerase chain reaction, viral cultures, and flow cytometry. Months after initial presentation, an anterior chamber angle mass developed and a biopsy identified retinoblastoma cells. The patient underwent plaque radiotherapy of the cornea and systemic chemotherapy. The patient regained good vision and is tumor-free at 13 months. Anterior inflammation is a rare form of masquerade syndrome associated with retinoblastoma; however, it tends to be associated with diffuse posterior segment retinoblastoma when it does occur. Diffuse anterior retinoblastoma is a rare form of retinoblastoma with no apparent focus in the retina. Ultimately, our patient developed an anterior chamber angle lesion, which was biopsied and proven to be retinoblastoma. Unusual corneal endotheliitis-like findings in children that are not responsive to conventional treatment should raise the clinician's suspicion of malignancy, even when no retinal lesion is detected.

  6. Crypsis via leg clustering: twig masquerading in a spider.

    PubMed

    Zhang, Shichang; Mao, Kuei-Kai; Lin, Po-Ting; Ho, Chiu-Ju; Hung, Wei; Piorkowski, Dakota; Liao, Chen-Pan; Tso, I-Min

    2015-03-01

    The role of background matching in camouflage has been extensively studied. However, contour modification has received far less attention, especially in twig-mimicking species. Here, we studied this deceptive strategy by revealing a special masquerade tactic, in which the animals protract and cluster their legs linearly in the same axis with their bodies when resting, using the spider Ariamnes cylindrogaster as a model. We used cardboard papers to construct dummies resembling spiders in appearance and colour. To differentiate the most important factors in the concealment effect, we manipulated body size (long or short abdomen) and resting postures (leg clustered or spread) of the dummies and recorded the responses of predators to different dummy types in the field. The results showed that dummies with clustered legs received significantly less attention from predators, regardless of the body length. Thus, we conclude that A. cylindrogaster relies on the resting posture rather than body size for predator avoidance. This study provides, to the best of our knowledge, empirical evidence for the first time that twig-mimicking species can achieve effective camouflage by contour modification.

  7. Recurrent angio-fibroma of breast masquerading as phyllodes tumor.

    PubMed

    Chaurasia, Jai K; Alam, Feroz; Shadan, Mariam; Naim, Mohammed

    2015-01-01

    A young Indian female presented with a recurring tumor in the right breast masquerading as phyllodes tumor. Patient had history of five times excision and recurrences of the tumor, diagnosed as fibrous phyllodes of the breast. Presently, a well-circumscribed tumor of about 10 cm size, comprising of benign fibrous-angiomatous tissue with evidence of foci of pyogenic vasculitis was observed. Immuno-histochemical markers for the myo-epithelial and epithelial elements excluded the possibility of fibrous phyllodes, inflammatory myofibroblastic tumor, desmoid fibromatosis, and metaplastic carcinoma. The present findings were diagnostic of an inflammatory angio-fibroma of the right breast, not reported in the earlier literature. The observations indicated that the female breast may be susceptible to spontaneous productive and common-antibiotic-resistant focal septic vascular inflammation giving rise to angio-fibromatous proliferation producing a well-defined tumor mass in the breast, distinguishable from the other breast lesions by the connective tissue stains and immuno-histochemical markers.

  8. Cross-reactivity and masqueraders in seafood reactions.

    PubMed

    Banks, Taylor A; Gada, Satyen M

    2013-01-01

    Confounding variables play a significant role in many adverse seafood reactions and a clear understanding of these factors is important in properly characterizing reactions associated with potential masqueraders and mimics. Although the medical literature is replete with reviews of seafood hypersensitivity and reports of cross-reactive and newly characterized allergens, there has not been a recent effort to provide an updated overview of the several processes that may lead clinicians to draw incorrect conclusions in evaluating reported reactions to seafood. Ranging from seafood intoxications to other nonallergic or complex seafood reactions, these events can easily be misconstrued as representing a seafood IgE-mediated allergy. Among these are the more familiar topics of cross-reactivity and scombroid intoxication, and those with a still evolving understanding such as ciguatera fish poisoning and Anisakis reactions. This article seeks to provide an accessible but comprehensive summary of the relevant information surrounding these confounders in assessing adverse reactions to seafood. Such knowledge may be instrumental in unraveling complex or otherwise unclear presentations and aid clinicians in accurately evaluating and managing patients with reported seafood reactions.

  9. Crypsis via leg clustering: twig masquerading in a spider

    PubMed Central

    Zhang, Shichang; Mao, Kuei-Kai; Lin, Po-Ting; Ho, Chiu-Ju; Hung, Wei; Piorkowski, Dakota; Liao, Chen-Pan; Tso, I-Min

    2015-01-01

    The role of background matching in camouflage has been extensively studied. However, contour modification has received far less attention, especially in twig-mimicking species. Here, we studied this deceptive strategy by revealing a special masquerade tactic, in which the animals protract and cluster their legs linearly in the same axis with their bodies when resting, using the spider Ariamnes cylindrogaster as a model. We used cardboard papers to construct dummies resembling spiders in appearance and colour. To differentiate the most important factors in the concealment effect, we manipulated body size (long or short abdomen) and resting postures (leg clustered or spread) of the dummies and recorded the responses of predators to different dummy types in the field. The results showed that dummies with clustered legs received significantly less attention from predators, regardless of the body length. Thus, we conclude that A. cylindrogaster relies on the resting posture rather than body size for predator avoidance. This study provides, to the best of our knowledge, empirical evidence for the first time that twig-mimicking species can achieve effective camouflage by contour modification. PMID:26064622

  10. Infradiaphragmatic Extralobar Pulmonary Sequestration: Masquerading as Suprarenal Mass

    PubMed Central

    Kalenahalli, Kiran V.; Garg, Navneet; Goolahally, Lakshmikantha N.; Reddy, Somasekhara P.; Iyengar, Jayanth

    2013-01-01

    Pulmonary sequestration is a rare malformation, wherein a portion of lung is non-functional and is not in normal continuity with the tracheo-bronchial tree, and may derive its blood supply from systemic vessels. Two types are described: Intralobar and extralobar types. Intralobar sequestration is more common type, which shares visceral pleura of the involved lobe and is localized within the normal pulmonary parenchyma. Whereas extralobar forms are uncommon and are totally separate from the lung and usually have own covering. Infra-diaphragmatic pulmonary sequestration is of extralobar type and is extremely rare, and usually is associated with other congenital malformations. We present an extremely rare case of isolated infra-diaphragmatic pulmonary sequestration which was antenatally detected and followed up with postnatal CT scan, where it masqueraded as suprarenal mass, and was surgically treated. This case emphasises to add a differential diagnosis of malformation in congenital supra-renal masses, which remain stable in size and appearance, and hence avoid immediate surgery. PMID:24251262

  11. AngioVac extraction of intra-atrial hepatoma masquerading as PICC-associated thrombus.

    PubMed

    Abboud, Samir; Raparia, Kirtee; Ubago, Julianne M; Resnick, Scott

    2016-01-01

    Thrombus associated with peripherally inserted central catheterization is not uncommon. Treatment is typically conservative; however, more aggressive therapies can be considered in patients with tenuous medical condition. The authors present a patient with metastatic hepatocellular carcinoma masquerading as peripherally inserted central catheter-associated intra-atrial thrombus, subsequently removed via vacuum-assisted mechanical thrombectomy.

  12. Burkitt’s lymphoma masquerading as appendicitis – two case reports and review of the literature

    PubMed Central

    2014-01-01

    Two cases of Burkitt’s lymphoma masquerading as appendicitis are reported herein. The diagnoses were made post-operatively from the appendix specimen in one case and from an ileocecal resection specimen for cecal fistula complicating an appendicectomy in the second case. These cases highlight the importance of routine histological examination of appendicectomy specimens. PMID:24942062

  13. Neuromyelitis Optica Masquerading as Lumbosacral Radiculopathy: A Case Report

    PubMed Central

    2016-01-01

    Neuromyelitis optica spectrum disorders (NMOSD) is a demyelinating syndrome of the central nervous system. This case report describes a 31-year-old woman whose electromyography revealed radiculopathy in the left L5-S1 spinal segment without anatomical abnormalities on lumbosacral magnetic resonance imaging (MRI). She was diagnosed with NMOSD based on gadolinium contrast whole spine and brain MRI and anti-aquaporin-4 antibody findings. Her peripheral nervous system might have been damaged during the early course of NMOSD. Therefore, it is necessary to consider NMOSD for patients who have radiculopathy in electromyography if lumbosacral MRI shows no abnormalities. PMID:27847726

  14. Peripheral nerve proteins as potential autoantigens in acute and chronic inflammatory demyelinating polyneuropathies.

    PubMed

    Lim, Jia Pei; Devaux, Jérôme; Yuki, Nobuhiro

    2014-10-01

    Guillain-Barré syndrome is classified into acute inflammatory demyelinating polyneuropathy and acute motor axonal neuropathy. Whereas autoantibodies to GM1 or GD1a induce the development of acute motor axonal neuropathy, pathogenic autoantibodies have yet to be identified in acute inflammatory demyelinating polyneuropathy and chronic inflammatory demyelinating polyneuropathy. This review highlights the importance of autoantibodies to peripheral nerve proteins in the physiopathology of acute and chronic inflammatory demyelinating polyneuropathies. Moreover, we listed up other potential antigens, which may become helpful biomarkers for acquired, dysimmune demyelinating neuropathies based on their critical functions during myelination and their implications in hereditary demyelinating neuropathies.

  15. Diagnosis and treatment of chronic acquired demyelinating polyneuropathies.

    PubMed

    Latov, Norman

    2014-08-01

    Chronic neuropathies are operationally classified as primarily demyelinating or axonal, on the basis of electrodiagnostic or pathological criteria. Demyelinating neuropathies are further classified as hereditary or acquired-this distinction is important, because the acquired neuropathies are immune-mediated and, thus, amenable to treatment. The acquired chronic demyelinating neuropathies include chronic inflammatory demyelinating polyneuropathy (CIDP), neuropathy associated with monoclonal IgM antibodies to myelin-associated glycoprotein (MAG; anti-MAG neuropathy), multifocal motor neuropathy (MMN), and POEMS syndrome. They have characteristic--though overlapping--clinical presentations, are mediated by distinct immune mechanisms, and respond to different therapies. CIDP is the default diagnosis if the neuropathy is demyelinating and no other cause is found. Anti-MAG neuropathy is diagnosed on the basis of the presence of anti-MAG antibodies, MMN is characterized by multifocal weakness and motor conduction blocks, and POEMS syndrome is associated with IgG or IgA λ-type monoclonal gammopathy and osteosclerotic myeloma. The correct diagnosis, however, can be difficult to make in patients with atypical or overlapping presentations, or nondefinitive laboratory studies. First-line treatments include intravenous immunoglobulin (IVIg), corticosteroids or plasmapheresis for CIDP; IVIg for MMN; rituximab for anti-MAG neuropathy; and irradiation or chemotherapy for POEMS syndrome. A correct diagnosis is required for choosing the appropriate treatment, with the aim of preventing progressive neuropathy.

  16. Diffusion kurtosis imaging probes cortical alterations and white matter pathology following cuprizone induced demyelination and spontaneous remyelination

    PubMed Central

    Guglielmetti, C.; Veraart, J.; Roelant, E.; Mai, Z.; Daans, J.; Van Audekerke, J.; Naeyaert, M.; Vanhoutte, G.; Delgado y Palacios, R.; Praet, J.; Fieremans, E.; Ponsaerts, P.; Sijbers, J.; Van der Linden, A.; Verhoye, M.

    2016-01-01

    cuprizone and control groups, hence highlighting their ability to detect both acute and long lasting changes. Interestingly, WMTI-derived metrics showed the aptitude to distinguish between the different stage of the disease. Both the intra-axonal diffusivity (Da) and the AWF were found to be decreased in the cuprizone treated group, Da specifically decreased during the acute inflammatory demyelinating phase whereas the AWF decrease was associated to the spontaneous remyelination and the recovery period. Altogether our results demonstrate that DKI is sensitive to alterations of cortical areas and provides, along with WMTI metrics, information that is complementary to DT-derived metrics for the characterization of demyelination in both white and grey matter and subsequent inflammatory processes associated with a demyelinating event. PMID:26525654

  17. Diffusion kurtosis imaging probes cortical alterations and white matter pathology following cuprizone induced demyelination and spontaneous remyelination.

    PubMed

    Guglielmetti, C; Veraart, J; Roelant, E; Mai, Z; Daans, J; Van Audekerke, J; Naeyaert, M; Vanhoutte, G; Delgado Y Palacios, R; Praet, J; Fieremans, E; Ponsaerts, P; Sijbers, J; Van der Linden, A; Verhoye, M

    2016-01-15

    cuprizone and control groups, hence highlighting their ability to detect both acute and long lasting changes. Interestingly, WMTI-derived metrics showed the aptitude to distinguish between the different stages of the disease. Both the intra-axonal diffusivity (Da) and the AWF were found to be decreased in the cuprizone treated group, Da specifically decreased during the acute inflammatory demyelinating phase whereas the AWF decrease was associated to the spontaneous remyelination and the recovery period. Altogether our results demonstrate that DKI is sensitive to alterations of cortical areas and provides, along with WMTI metrics, information that is complementary to DT-derived metrics for the characterization of demyelination in both white and grey matter and subsequent inflammatory processes associated with a demyelinating event.

  18. Chronic inflammatory demyelinating polyneuropathy associated with primary biliary cirrhosis.

    PubMed

    Murata, Ken-ya; Ishiguchi, Hiroshi; Ando, Ryuki; Miwa, Hideto; Kondo, Tomoyoshi

    2013-12-01

    We report a patient with chronic inflammatory demyelinating polyneuropathy associated with primary biliary cirrhosis (PBC). Except for minimal biochemical abnormalities, clinical symptoms of PBC were not observed, and we diagnosed our patient with asymptomatic PBC from the results of a liver biopsy. Although the patient noticed little muscle weakness, an electrophysiological study demonstrated slow conduction velocities and prolonged distal latencies, with definite conduction blocks in the median, ulnar, and tibial nerves. The disturbed sensory pattern was asymmetrical, and sensory nerve action potentials were not evoked. From these observations, we diagnosed this patient with chronic inflammatory demyelinating polyneuropathy. Neuropathy associated with PBC is very rare. We must differentiate demyelinating neuropathy with PBC in patients with asymmetrical sensory dominant neuropathy with high immunoglobulin M titers, and investigate for the presence of anti-mitochondrial antibodies to rule out a complication of asymptomatic PBC.

  19. Accumulation of Extracellular Matrix in Advanced Lesions of Canine Distemper Demyelinating Encephalitis.

    PubMed

    Seehusen, Frauke; Al-Azreg, Seham A; Raddatz, Barbara B; Haist, Verena; Puff, Christina; Spitzbarth, Ingo; Ulrich, Reiner; Baumgärtner, Wolfgang

    2016-01-01

    In demyelinating diseases, changes in the quality and quantity of the extracellular matrix (ECM) may contribute to demyelination and failure of myelin repair and axonal sprouting, especially in chronic lesions. To characterize changes in the ECM in canine distemper demyelinating leukoencephalitis (DL), histochemical and immunohistochemical investigations of formalin-fixed paraffin-embedded cerebella using azan, picrosirius red and Gomori`s silver stain as well as antibodies directed against aggrecan, type I and IV collagen, fibronectin, laminin and phosphacan showed alterations of the ECM in CDV-infected dogs. A significantly increased amount of aggrecan was detected in early and late white matter lesions. In addition, the positive signal for collagens I and IV as well as fibronectin was significantly increased in late lesions. Conversely, the expression of phosphacan was significantly decreased in early and more pronounced in late lesions compared to controls. Furthermore, a set of genes involved in ECM was extracted from a publically available microarray data set and was analyzed for differential gene expression. Gene expression of ECM molecules, their biosynthesis pathways, and pro-fibrotic factors was mildly up-regulated whereas expression of matrix remodeling enzymes was up-regulated to a relatively higher extent. Summarized, the observed findings indicate that changes in the quality and content of ECM molecules represent important, mainly post-transcriptional features in advanced canine distemper lesions. Considering the insufficiency of morphological regeneration in chronic distemper lesions, the accumulated ECM seems to play a crucial role upon regenerative processes and may explain the relatively small regenerative potential in late stages of this disease.

  20. Inducible Expression of CXCL1 within the Central Nervous System Amplifies Viral-Induced Demyelination

    PubMed Central

    Marro, Brett S.; Grist, Jonathan J.

    2016-01-01

    The functional role of the ELR+ chemokine CXCL1 in host defense and disease following infection of the CNS with the neurotropic JHM strain of mouse hepatitis virus (JHMV) was examined. Mice in which expression of CXCL1 is under the control of a tetracycline-inducible promoter active within glial fibrillary acidic protein–positive cells were generated and this allowed for selectively increasing CNS expression of CXCL1 in response to JHMV infection and evaluating the effects on neuroinflammation, control of viral replication, and demyelination. Inducible expression of CNS-derived CXCL1 resulted in increased levels of CXCL1 protein within the serum, brain, and spinal cord that correlated with increased frequency of Ly6G+CD11b+ neutrophils present within the CNS. Elevated levels of CXCL1 did not influence the generation of virus-specific T cells, and there was no difference in control of JHMV replication compared with control mice, indicating that T cell infiltration into the CNS is CXCL1-independent. Sustained CXCL1 expression within the CNS resulted in increased mortality that correlated with elevated neutrophil infiltration, diminished numbers of mature oligodendrocytes, and an increase in the severity of demyelination. Neutrophil ablation in CXCL1-transgenic mice reduced the severity of demyelination in mice, arguing for a role for these cells in white matter damage. Collectively, these findings illustrate that sustained CXCL1 expression amplifies the severity of white matter damage and that neutrophils can contribute to this process in a model of viral-induced neurologic disease. PMID:26773148

  1. Accumulation of Extracellular Matrix in Advanced Lesions of Canine Distemper Demyelinating Encephalitis

    PubMed Central

    Seehusen, Frauke; Al-Azreg, Seham A.; Raddatz, Barbara B.; Haist, Verena; Puff, Christina; Spitzbarth, Ingo; Ulrich, Reiner; Baumgärtner, Wolfgang

    2016-01-01

    In demyelinating diseases, changes in the quality and quantity of the extracellular matrix (ECM) may contribute to demyelination and failure of myelin repair and axonal sprouting, especially in chronic lesions. To characterize changes in the ECM in canine distemper demyelinating leukoencephalitis (DL), histochemical and immunohistochemical investigations of formalin-fixed paraffin-embedded cerebella using azan, picrosirius red and Gomori`s silver stain as well as antibodies directed against aggrecan, type I and IV collagen, fibronectin, laminin and phosphacan showed alterations of the ECM in CDV-infected dogs. A significantly increased amount of aggrecan was detected in early and late white matter lesions. In addition, the positive signal for collagens I and IV as well as fibronectin was significantly increased in late lesions. Conversely, the expression of phosphacan was significantly decreased in early and more pronounced in late lesions compared to controls. Furthermore, a set of genes involved in ECM was extracted from a publically available microarray data set and was analyzed for differential gene expression. Gene expression of ECM molecules, their biosynthesis pathways, and pro-fibrotic factors was mildly up-regulated whereas expression of matrix remodeling enzymes was up-regulated to a relatively higher extent. Summarized, the observed findings indicate that changes in the quality and content of ECM molecules represent important, mainly post-transcriptional features in advanced canine distemper lesions. Considering the insufficiency of morphological regeneration in chronic distemper lesions, the accumulated ECM seems to play a crucial role upon regenerative processes and may explain the relatively small regenerative potential in late stages of this disease. PMID:27441688

  2. Motor variant of chronic inflammatory demyelinating polyneuropathy in a child.

    PubMed

    Sinno, Durriyah D; Darras, Basil T; Yamout, Bassem I; Rebeiz, Jean G; Mikati, Mohamad A

    2008-06-01

    Only 2 cases of pure motor chronic demyelinating inflammatory polyneuropathy in the pediatric age group have been reported in the literature. We report on a motor variant of chronic demyelinating inflammatory polyneuropathy with anti-ganglioside antibodies, diagnosed in a 5-year-old girl who presented with progressive motor weakness over a period of 12 months with no sensory involvement. She initially responded partially to intravenous immunoglobulin therapy (1 gm/kg/month for 6 months), and then demonstrated sustained but incomplete improvement on chronic prednisone therapy (1-2 mg/kg/day), on which she has continued since 1 year and 4 months after her initial presentation 3 years ago.

  3. Electrophysiologic features of inherited demyelinating neuropathies: a reappraisal.

    PubMed

    Lewis, R A; Sumner, A J

    1999-09-14

    The observation that inherited demyelinating neuropathies tend to have uniform conduction slowing and acquired disorders (CIDP and variants) have nonuniform or multifocal slowing was made before the identification of genetic defects of specific myelin constituents that cause the different forms of Charcot-Marie-Tooth and other inherited disorders involving peripheral nerve myelin. It is becoming clear that the electrophysiologic aspects of these disorders are more complex than previously realized. We review the current information available on the electrophysiologic features of the inherited demyelinating neuropathies in hopes of clarifying the clinical electrodiagnostic features of these disorders as well as to shed light on the physiologic consequences of the different genetic mutations.

  4. Experimental Demyelination and Remyelination of Murine Spinal Cord by Focal Injection of Lysolecithin

    PubMed Central

    Keough, Michael B.; Jensen, Samuel K.; Yong, V. Wee

    2015-01-01

    Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system characterized by plaque formation containing lost oligodendrocytes, myelin, axons, and neurons. Remyelination is an endogenous repair mechanism whereby new myelin is produced subsequent to proliferation, recruitment, and differentiation of oligodendrocyte precursor cells into myelin-forming oligodendrocytes, and is necessary to protect axons from further damage. Currently, all therapeutics for the treatment of multiple sclerosis target the aberrant immune component of the disease, which reduce inflammatory relapses but do not prevent progression to irreversible neurological decline. It is therefore imperative that remyelination-promoting strategies be developed which may delay disease progression and perhaps reverse neurological symptoms. Several animal models of demyelination exist, including experimental autoimmune encephalomyelitis and curprizone; however, there are limitations in their use for studying remyelination. A more robust approach is the focal injection of toxins into the central nervous system, including the detergent lysolecithin into the spinal cord white matter of rodents. In this protocol, we demonstrate that the surgical procedure involved in injecting lysolecithin into the ventral white matter of mice is fast, cost-effective, and requires no additional materials than those commercially available. This procedure is important not only for studying the normal events involved in the remyelination process, but also as a pre-clinical tool for screening candidate remyelination-promoting therapeutics. PMID:25867716

  5. Clinical and electrophysiological parameters distinguishing acute-onset chronic inflammatory demyelinating polyneuropathy from acute inflammatory demyelinating polyneuropathy.

    PubMed

    Dionne, Annie; Nicolle, Michael W; Hahn, Angelika F

    2010-02-01

    Up to 16% of chronic inflammatory demyelinating polyneuropathy (CIDP) patients may present acutely. We performed a retrospective chart review on 30 acute inflammatory demyelinating polyneuropathy (AIDP) and 15 acute-onset CIDP (A-CIDP) patients looking for any clinical or electrophysiological parameters that might differentiate AIDP from acutely presenting CIDP. A-CIDP patients were significantly more likely to have prominent sensory signs. They were significantly less likely to have autonomic nervous system involvement, facial weakness, a preceding infectious illness, or need for mechanical ventilation. With regard to electrophysiological features, neither sural-sparing pattern, sensory ratio >1, nor the presence of A-waves was different between the two groups. This study suggests that patients presenting acutely with a demyelinating polyneuropathy and the aforementioned clinical features should be closely monitored as they may be more likely to have CIDP at follow-up.

  6. Optic Nerve Sheath Meningioma Masquerading as Optic Neuritis

    PubMed Central

    Alroughani, R.; Behbehani, R.

    2016-01-01

    Optic neuritis is a common presentation of demyelinating disorders such as multiple sclerosis. It typically presents with acute painful monocular vision loss, whereas chronic optic neuropathy can be caused by compressive lesions along the anterior visual pathway, genetic, toxic, or nutritional causes. We report an unusual presentation mimicking optic neuritis, which was subsequently diagnosed as optic nerve sheath meningioma (ONSM). Misinterpretation of white matter lesions on MRI of brain and the failure to image the optic nerves at the time of acute loss of vision led to the misdiagnosis of optic neuritis in this case. A comprehensive accurate history and ordering the appropriate imaging modality remain paramount in diagnosing progressive visual deterioration. PMID:26904329

  7. Changes of CXCL12, CXCL14 and PDGF levels in the brain of patients with idiopathic demyelinating optic neuritis and neuromyelitis optica.

    PubMed

    Tingjun, Chen; Zhaohui, Li; Zhaocai, Jiang; Zihao, Liu; Quangang, Xu; Dehui, Huang; Qing, Lin; Shihui, Wei

    2015-02-15

    The CXC chemokines (CXC-motif ligand 12 and CXC-motif ligand 14) and platelet-derived growth factor are suggested to modulate remyelination in the course of many demyelinating diseases. The present study compared the difference in the brain levels of these chemokines between patients with idiopathic demyelinating optic neuritis (IDON) and neuromyelitis optica (NMO) by measuring their concentrations in the cerebrospinal fluid using an enzyme linked immunosorbent assay. Our data indicate that the prognosis of neuritis depends on the remyelinating process that is impaired due to decreased chemokines. The much lower levels of chemokines would specifically indicate the severe neuritis, such as NMO.

  8. Reversible Demyelination, Blood-Brain Barrier Breakdown, and Pronounced Neutrophil Recruitment Induced by Chronic IL-1 Expression in the Brain

    PubMed Central

    Ferrari, Carina C.; Depino, Amaicha M.; Prada, Federico; Muraro, Nara; Campbell, Sandra; Podhajcer, Osvaldo; Perry, V. Hugh; Anthony, Daniel C.; Pitossi, Fernando J.

    2004-01-01

    Interleukin-1β (IL-1) expression is associated with a spectrum of neuroinflammatory processes related to chronic neurodegenerative diseases. The single-bolus microinjection of IL-1 into the central nervous system (CNS) parenchyma gives rise to delayed and localized neutrophil recruitment, transient blood-brain barrier (BBB) breakdown, but no overt damage to CNS integrity. However, acute microinjections of IL-1 do not mimic the chronic IL-1 expression, which is a feature of many CNS diseases. To investigate the response of the CNS to chronic IL-1 expression, we injected a recombinant adenovirus expressing IL-1 into the striatum. At the peak of IL-1 expression (days 8 and 14 post-injection), there was a marked recruitment of neutrophils, vasodilatation, and breakdown of the BBB. Microglia and astrocyte activation was evident during the first 14 days post-injection. At days 8 and 14, extensive demyelination was observed but the number of neurons was not affected by any treatment. Finally, at 30 days, signs of inflammation were no longer present, there was evidence of tissue reorganization, the BBB was intact, and the process of remyelination was noticeable. In summary, our data show that chronic expression of IL-1, in contrast to its acute delivery, can reversibly damage CNS integrity and implicates this cytokine or downstream components as major mediators of demyelination in chronic inflammatory and demyelinating diseases. PMID:15509551

  9. The neural androgen receptor: a therapeutic target for myelin repair in chronic demyelination.

    PubMed

    Hussain, Rashad; Ghoumari, Abdel M; Bielecki, Bartosz; Steibel, Jérôme; Boehm, Nelly; Liere, Philippe; Macklin, Wendy B; Kumar, Narender; Habert, René; Mhaouty-Kodja, Sakina; Tronche, François; Sitruk-Ware, Regine; Schumacher, Michael; Ghandour, M Said

    2013-01-01

    Myelin regeneration is a major therapeutic goal in demyelinating diseases, and the failure to remyelinate rapidly has profound consequences for the health of axons and for brain function. However, there is no efficient treatment for stimulating myelin repair, and current therapies are limited to anti-inflammatory agents. Males are less likely to develop multiple sclerosis than females, but often have a more severe disease course and reach disability milestones at an earlier age than females, and these observations have spurred interest in the potential protective effects of androgens. Here, we demonstrate that testosterone treatment efficiently stimulates the formation of new myelin and reverses myelin damage in chronic demyelinated brain lesions, resulting from the long-term administration of cuprizone, which is toxic for oligodendrocytes. In addition to the strong effect of testosterone on myelin repair, the number of activated astrocytes and microglial cells returned to low control levels, indicating a reduction of neuroinflammatory responses. We also identify the neural androgen receptor as a novel therapeutic target for myelin recovery. After the acute demyelination of cerebellar slices in organotypic culture, the remyelinating actions of testosterone could be mimicked by 5α-dihydrotestosterone, a metabolite that is not converted to oestrogens, and blocked by the androgen receptor antagonist flutamide. Testosterone treatment also failed to promote remyelination after chronic cuprizone-induced demyelination in mice with a non-functional androgen receptor. Importantly, testosterone did not stimulate the formation of new myelin sheaths after specific knockout of the androgen receptor in neurons and macroglial cells. Thus, the neural brain androgen receptor is required for the remyelination effect of testosterone, whereas the presence of the receptor in microglia and in peripheral tissues is not sufficient to enhance remyelination. The potent synthetic

  10. Invasive amebiasis and ameboma formation presenting as a rectal mass: An uncommon case of malignant masquerade at a western medical center

    PubMed Central

    Hardin, Rosemarie E; Ferzli, George S; Zenilman, Michael E; Gadangi, Pratap K; Bowne, Wilbur B

    2007-01-01

    A 54-year-old man presented with rectal pain and bleeding secondary to ulcerated, necrotic rectal and cecal masses that resembled colorectal carcinoma upon colonoscopy. These masses were later determined to be benign amebomas caused by invasive Entamoeba histolytica, which regressed completely with medical therapy. In Western countries, the occurrence of invasive protozoan infection with formation of amebomas is very rare and can mistakenly masquerade as a neoplasm. Not surprisingly, there have been very few cases reported of this clinical entity within the United States. Moreover, we report a patient that had an extremely rare occurrence of two synchronous lesions, one involving the rectum and the other situated in the cecum. We review the current literature on the pathogenesis of invasive E. histolytica infection and ameboma formation, as well as management of this rare disease entity at a western medical center. PMID:17948943

  11. Therapeutic Value or Harm of Neuregulin 1 in Demyelinating Disorders

    DTIC Science & Technology

    2012-10-01

    Abberant neuregulin 1 signaling in amyotrophic lateral sclerosis . J Neuropath Exp Neurol, 71:104-15. APPENDICES: none SUPPORTING OAT A: Here is some new...Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT It is still not clear whether the primary process in multiple sclerosis is degenerative... sclerosis and other demyelinating disorders. 15. SUBJECT TERMS- Neuregulin, Multiple sclerosis , myelin, axogilial interactions, therapeutics. 16

  12. Subacute CNS Demyelination after Treatment with Nivolumab for Melanoma.

    PubMed

    Maurice, Catherine; Schneider, Raphael; Kiehl, Tim-Rasmus; Bavi, Prashant; Roehrl, Michael H A; Mason, Warren P; Hogg, David

    2015-12-01

    Immunotherapy with monoclonal antibodies targeting cytotoxic T-lymphocyte antigen 4 (CTLA-4) or programmed cell death 1 (PD-1) has improved the survival of patients with metastatic melanoma. These agents carry a certain risk of adverse immune-related events. We present a patient with widely metastatic melanoma who was initially treated with ipilimumab and subsequently with nivolumab. After four infusions of nivolumab, he developed subacute multifocal central nervous system (CNS) demyelination. Nivolumab was discontinued and, despite immunosuppressive therapy, the largest lesion progressed significantly, whereas another lesion showed radiographic improvement. After further progression, the patient succumbed to his CNS lesions 4 months later. Autopsy revealed extensive demyelination, a mild multifocal T-cell-rich perivascular lymphoid infiltrate, abundant macrophages, and necrosis. There was no metastatic melanoma in the brain. CNS demyelination has not been described in association with nivolumab. We hypothesize that the combination therapy of ipilimumab and subsequent nivolumab accounted for the severity of the demyelinating process in this patient. This case, with comprehensive clinical, molecular, and neuropathologic characterization, illustrates the need for awareness of these potential CNS complications with the use of multiple checkpoint inhibitors.

  13. Microglial cell activation in demyelinating canine distemper lesions.

    PubMed

    Stein, Veronika M; Czub, Markus; Schreiner, Nicole; Moore, Peter F; Vandevelde, Marc; Zurbriggen, Andreas; Tipold, Andrea

    2004-08-01

    Microglia cells are the principal immune effector elements of the brain responding to any pathological event. To elucidate the possible role of microglia in initial non-inflammatory demyelination in canine distemper virus (CDV) infection, microglia from experimentally CDV infected dogs were isolated ex vivo by density gradient centrifugation and characterized immunophenotypically and functionally using flow cytometry. Results from dogs with demyelinating lesions were compared to results from recovered dogs and two healthy controls. CDV antigen could be detected in microglia of dogs with histopathologically confirmed demyelination. Microglia of these dogs showed marked upregulation of the surface molecules CD18, CD11b, CD11c, CD1c, MHC class I and MHC class II and a tendency for increased expression intensity of ICAM-1 (CD54), B7-1 (CD80), B7-2 (CD86), whereas no increased expression was found for CD44 and CD45. Functionally, microglia exhibited distinctly enhanced phagocytosis and generation of reactive oxygen species (ROS). It was concluded that in CDV infection, there is a clear association between microglial activation and demyelination. This strongly suggests that microglia contribute to acute myelin destruction in distemper.

  14. Late central demyelination after Fischer's syndrome: MRI studies.

    PubMed Central

    Ferrer, X; Ellie, E; Larrivière, M; Deleplanque, B; Lagueny, A; Julien, J

    1993-01-01

    The case of a patient who presented with clinical, electrophysiological, and MRI evidence of central demyelination is described. The patient had been admitted to hospital for Fischer's syndrome a few years previously. The association of these two events suggests that central and peripheral myelinopathy may be related in Fischer's syndrome. PMID:8509787

  15. Kallikrein 6 regulates early CNS demyelination in a viral model of multiple sclerosis.

    PubMed

    Scarisbrick, Isobel A; Yoon, Hyesook; Panos, Michael; Larson, Nadya; Blaber, Sachiko I; Blaber, Michael; Rodriguez, Moses

    2012-09-01

    Kallikrein 6 (Klk6) is a secreted serine protease that is elevated in active multiple sclerosis lesions and patient sera. To further evaluate the involvement of Klk6 in chronic progressive demyelinating disease, we determined its expression in the brain and spinal cord of SJL mice infected with Theiler's murine encephalomyelitis virus (TMEV) and assessed the effects of Klk6-neutralizing antibodies on disease progression. Klk6 RNA expression was elevated in the brain and spinal cord by 7 days postinfection (dpi). Thereafter, Klk6 expression persisted primarily in the spinal cord reaching a peak of fivefold over controls at mid-chronic stages (60 dpi-120 dpi). Significant elevations in Klk6 RNA were also induced in splenocytes stimulated with viral capsid proteins in vitro and in activated human acute monocytic leukemia cells. Klk6-neutralizing antibodies reduced TMEV-driven brain and spinal cord pathology and delayed-type hypersensitivity (DTH) responses when examined at early chronic time points (40 dpi). Reductions in spinal cord pathology included a decrease in activated monocytes/microglia and reductions in the loss of myelin basic protein (MBP). By 180 dpi, pathology scores no longer differed between groups. These findings point to regulatory activities for Klk6 in the development and progression of central nervous system (CNS) inflammation and demyelination that can be effectively targeted through the early chronic stages with neutralizing antibody.

  16. MiR-146a promotes remyelination in a cuprizone model of demyelinating injury.

    PubMed

    Zhang, Jing; Zhang, Zheng Gang; Lu, Mei; Wang, Xinli; Shang, Xia; Elias, Stanton B; Chopp, Michael

    2017-04-21

    The death of mature oligodendrocytes (OLs) which are the sole myelinating cells of the central nervous system (CNS), leads to demyelination and functional deficits. Currently, there is lack of effective remyelination therapies for patients with demyelinating diseases. MicroRNAs (miRNAs) mediate OL function. We hypothesized that miR-146a, by inactivating interleukin-1 receptor-associated kinase 1 (IRAK1), promotes differentiation of oligodendrocyte progenitor cells (OPCs) and thereby enhances remyelination. To test this hypothesis, a demyelination model induced by a cuprizone (CPZ) diet was employed, in which C57BL/6J mice were fed with a CPZ diet for 5weeks. After termination of CPZ diet, the mice were randomly treated with continuous infusion of miR-146a mimics or mimic controls into the corpus callosum for 7days. Compared to the mimic control, infusion of miR-146a mimics facilitated remyelination assessed by increased myelin basic proteins in the corpus callosum, which was associated with augmentation of newly generated mature OLs. Infusion of miR-146a mimics also substantially elevated miR-146a levels in the corpus callosum and fluorescently tagged miR-146a mimics were mainly detected in OPCs. Western blot and double immmunofluorescent staining analysis showed that the miR-146a treatment considerably reduced IRAK1 protein levels and the number of IRAK1-positive cells, respectively. Collectively, these data indicate that exogenous miR-146a enhances remyelination, possibly by promoting OPCs to differentiate into myelinated OLs via targeting IRAK1.

  17. Inflammatory demyelination induces ependymal modifications concomitant to activation of adult (SVZ) stem cell proliferation.

    PubMed

    Pourabdolhossein, Fereshteh; Gil-Perotín, Sara; Garcia-Belda, Paula; Dauphin, Aurelien; Mozafari, Sabah; Tepavcevic, Vanja; Manuel Garcia Verdugo, Jose; Baron-Van Evercooren, Anne

    2017-05-01

    Ependymal cells (E1/E2) and ciliated B1cells confer a unique pinwheel architecture to the ventricular surface of the subventricular zone (SVZ), and their cilia act as sensors to ventricular changes during development and aging. While several studies showed that forebrain demyelination reactivates the SVZ triggering proliferation, ectopic migration, and oligodendrogenesis for myelin repair, the potential role of ciliated cells in this process was not investigated. Using conventional and lateral wall whole mount preparation immunohistochemistry in addition to electron microscopy in a forebrain-targeted model of experimental autoimmune encephalomyelitis (tEAE), we show an early decrease in numbers of pinwheels, B1 cells, and E2 cells. These changes were transient and simultaneous to tEAE-induced SVZ stem cell proliferation. The early drop in B1/E2 cell numbers was followed by B1/E2 cell recovery. While E1 cell division and ependymal ribbon disruption were never observed, E1 cells showed important morphological modifications reflected by their enlargement, extended cytoskeleton, and reinforced cell-cell junction complexes overtime, possibly reflecting protective mechanisms against ventricular insults. Finally, tEAE disrupted motile cilia planar cell polarity and cilia orientation in ependymal cells. Therefore, significant ventricular modifications in ciliated cells occur early in response to tEAE suggesting a role for these cells in SVZ stem cell signalling not only during development/aging but also during inflammatory demyelination. These observations may have major implications for understanding pathophysiology of and designing therapeutic approaches for inflammatory demyelinating diseases such as MS.

  18. Pulmonary Embolism Masquerading as High Altitude Pulmonary Edema at High Altitude.

    PubMed

    Pandey, Prativa; Lohani, Benu; Murphy, Holly

    2016-12-01

    Pandey, Prativa, Benu Lohani, and Holly Murphy. Pulmonary embolism masquerading as high altitude pulmonary edema at high altitude. High Alt Med Biol. 17:353-358, 2016.-Pulmonary embolism (PE) at high altitude is a rare entity that can masquerade as or occur in conjunction with high altitude pulmonary edema (HAPE) and can complicate the diagnosis and management. When HAPE cases do not improve rapidly with descent, other diagnoses, including PE, ought to be considered. From 2013 to 2015, we identified eight cases of PE among 303 patients with initial diagnosis of HAPE. Upon further evaluation, five had deep vein thrombosis (DVT). One woman had a contraceptive ring and seven patients had no known thrombotic risks. PE can coexist with or mimic HAPE and should be considered in patients presenting with shortness of breath from high altitude regardless of thrombotic risk.

  19. Pulmonary Embolism Masquerading as High Altitude Pulmonary Edema at High Altitude

    PubMed Central

    Lohani, Benu; Murphy, Holly

    2016-01-01

    Abstract Pandey, Prativa, Benu Lohani, and Holly Murphy. Pulmonary embolism masquerading as high altitude pulmonary edema at high altitude. High Alt Med Biol. 17:353–358, 2016.—Pulmonary embolism (PE) at high altitude is a rare entity that can masquerade as or occur in conjunction with high altitude pulmonary edema (HAPE) and can complicate the diagnosis and management. When HAPE cases do not improve rapidly with descent, other diagnoses, including PE, ought to be considered. From 2013 to 2015, we identified eight cases of PE among 303 patients with initial diagnosis of HAPE. Upon further evaluation, five had deep vein thrombosis (DVT). One woman had a contraceptive ring and seven patients had no known thrombotic risks. PE can coexist with or mimic HAPE and should be considered in patients presenting with shortness of breath from high altitude regardless of thrombotic risk. PMID:27768392

  20. Allergic contact dermatitis to Plectranthus amboinicus masquerading as chronic leg ulcer.

    PubMed

    Chang, Shyue-Luen; Chang, Ya-Ching; Yang, Chin-Hsun; Hong, Hong-Shang

    2005-12-01

    This report discusses a case of a 69-year-old woman who developed chronic non-healing leg ulcers after long-term topical use of Plectranthus amboinicus. The ulcer was proven to be allergic contact dermatitis to P. amboinicus by a patch test. The ulcer healed after discontinuation of P. amboinicus. To the best of our knowledge, this is the first reported case of allergic contact dermatitis to P. amboinicus masquerading as chronic leg ulcer.

  1. T-cell lymphoma masquerading as extrapulmonary tuberculosis: case report and review of literature

    PubMed Central

    Ranjan, Piyush; Dutta, Sourabh; Kakkar, Aanchal; Goyal, Ankur; Vikram, Naval K.; Sharma, Mehar C.; Sood, Rita

    2015-01-01

    It is often difficult to establish confirmatory diagnosis in cases of extrapulmonary tuberculosis (TB) because of its paucibacillary nature and difficulty in accessing the involved organs. In several cases, empirical anti-tubercular treatment is started, and the patient is followed-up closely for response. In countries with high prevalence of TB, it is a reasonably good strategy and works most of the times. However, catastrophe may occur when aggressive lymphomas masquerade as TB. PMID:25949984

  2. Novel insight into Chronic Inflammatory Demyelinating Polineuropathy in APECED syndrome: molecular mechanisms and clinical implications in children.

    PubMed

    Valenzise, Mariella; Aversa, Tommaso; Salzano, Giuseppina; Zirilli, Giuseppina; De Luca, Filippo; Su, Maureen

    2017-01-19

    Autoimmune polyendocrinopathy-candidiasis-ectodermal-dystrophy (APECED) is a rare primary immunodeficiency disorder typically caused by homozygous AIRE gene mutation. It is characterized by the association of multiple autoimmune diseases, with a classical triad including chronic mucocutaneous candidiasis, hypoparathyroidism and adrenocortical failure. Its clinical spectrum has significantly enlarged in the last years with the apparence of new entities. One of these novel manifestations is the chronic inflammatory demyelinating polineuropathy (CIDP), that is characterized by involvement of peripheral nervous system, with nerve demyelination, progressive muscular weakness of both arms and legs and sensory loss. The identification of myelin protein zero as an important autoantigen (Ag) in CIDP may suggest the development of Ag-based therapies, such as Ag-specific DNA vaccination or infusion of Ag-coupled cells.

  3. Treatment of Chronic Inflammatory Demyelinating Polyneuropathy: From Molecular Bases to Practical Considerations

    PubMed Central

    Ripellino, Paolo; Fleetwood, Thomas; Cantello, Roberto; Comi, Cristoforo

    2014-01-01

    Chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune disease of the peripheral nervous system, in which both cellular and humoral immune responses are involved. The disease is clinically heterogeneous with some patients displaying pure motor form and others also showing a variable degree of sensory dysfunction; disease evolution may also differ from patient to patient, since monophasic, progressive, and relapsing forms are reported. Underlying such clinical variability there is probably a broad spectrum of molecular dysfunctions that are and will be the target of therapeutic strategies. In this review we first explore the biological bases of current treatments and subsequently we focus on the practical management that must also take into account pharmacoeconomic issues. PMID:24527207

  4. T lymphocyte-derived demyelinating activity in multiple sclerosis patients in relapse.

    PubMed Central

    Selmaj, K; Alam, R; Perkin, G D; Rose, F C

    1987-01-01

    Supernatants of cultured T lymphocytes of multiple sclerosis patients were tested for a demyelinating activity in rat cerebellum explant cultures. Supernatants of unstimulated T lymphocytes in seven out of 10 multiple sclerosis patients in relapse produced demyelination when checked by phase contrast microscopy. Supernatants of unstimulated T lymphocytes from healthy subjects did not produce demyelination, but when T cells were stimulated by phytohaemagglutinin (PHA), 50% of tested supernatants produced demyelination, which was, however, never as advanced as in multiple sclerosis supernatant treated cerebellum cultures. The demyelinating activity proved to be heat labile. Gel filtration study revealed two fractions of the demyelinating activity 12.5-29.0 kD and 43.0-66.0 kD. The results suggest that lymphokines can be directly involved in the pathogenesis of demyelination in multiple sclerosis. Images PMID:3495638

  5. The use of background matching vs. masquerade for camouflage in cuttlefish Sepia officinalis.

    PubMed

    Buresch, Kendra C; Mäthger, Lydia M; Allen, Justine J; Bennice, Chelsea; Smith, Neal; Schram, Jonathan; Chiao, Chuan-Chin; Chubb, Charles; Hanlon, Roger T

    2011-12-08

    Cuttlefish, Sepia officinalis, commonly use their visually-guided, rapid adaptive camouflage for multiple tactics to avoid detection or recognition by predators. Two common tactics are background matching and resembling an object (masquerade) in the immediate area. This laboratory study investigated whether cuttlefish preferentially camouflage themselves to resemble a three-dimensional (3D) object in the immediate visual field (via the mechanism of masquerade/deceptive resemblance) rather than the 2D benthic substrate surrounding them (via the mechanisms of background matching or disruptive coloration). Cuttlefish were presented with a combination of benthic substrates (natural rocks or artificial checkerboard and grey printouts) and 3D objects (natural rocks or cylinders with artificial checkerboards and grey printouts glued to the outside) with visual features known to elicit each of three camouflage body pattern types (Uniform, Mottle and Disruptive). Animals were tested for a preference to show a body pattern appropriate for the 3D object or the benthic substrate. Cuttlefish responded by masquerading as the 3D object, rather than resembling the benthic substrate, only when presented with a high-contrast object on a substrate of lower contrast. Contrast is, therefore, one important cue in the cuttlefish's preference to resemble 3D objects rather than the benthic substrate.

  6. Evidence of bird dropping masquerading by a spider to avoid predators

    PubMed Central

    Liu, Min-Hui; Blamires, Sean J.; Liao, Chen-Pan; -Min Tso, I.

    2014-01-01

    Masquerading comes at various costs and benefits. The principal benefit being the avoidance of predators. The orb-web spider Cyclosa ginnaga has a silver body and adds a white discoid-shaped silk decoration to its web. The size, shape and colour of C. ginnaga's body resemble, when viewed by the human eye against its decoration, a bird dropping. We therefore hypothesized that their body colouration might combine with its web decoration to form a bird dropping masquerade to protect it from predators. We measured the spectral reflectance of: (i) the spider's body, (ii) the web decoration, and (iii) bird droppings, in the field against a natural background and found that the colour of the spider bodies and decorations were indistinguishable from each other and from bird droppings when viewed by hymentopteran predators. We monitored the predatory attacks on C. ginnaga when the spider's body and/or its decorations were blackened and found that predator attack probabilities were greater when only the decorations were blackened. Accordingly, we concluded that C. ginnaga's decoration and body colouration forms a bird dropping masquerade, which reduces its probability of predation. PMID:24875182

  7. Lyme disease in athletes.

    PubMed

    DuPrey, Kevin M

    2015-01-01

    Lyme disease, a bacterial infection transmitted by ticks, is the most common vector-borne disease in the northern hemisphere. Athletes who train or compete in wooded environments in endemic regions are at increased risk of contracting Lyme disease. Variability in clinical presentation, masquerading symptoms, and limitations in testing may lead to misdiagnosis. Early diagnosis and treatment result in full recovery for most patients with Lyme disease; however symptoms may persist for months to years, especially when diagnosis is delayed. This article reviews the epidemiology, clinical manifestations, diagnosis, treatment, and prevention of Lyme disease, with focus on the athletic population.

  8. Ozone Therapy in Ethidium Bromide-Induced Demyelination in Rats: Possible Protective Effect.

    PubMed

    Salem, Neveen A; Assaf, Naglaa; Ismail, Manal F; Khadrawy, Yasser A; Samy, Mohga

    2016-08-01

    Multiple sclerosis, an autoimmune inflammatory disease of the central nervous system, is characterized by excessive demyelination. The study aimed to investigate the possible protective effect of ozone (O3) therapy in ethidium bromide (EB)-induced demyelination in rats either alone or in combination with corticosteroids in order to decrease the dose of steroid therapy. Rats were divided into Group (1) normal control rats received saline, Group (2) Sham-operated rats received saline, Group (3) Sham-operated rats received vehicle (oxygen), Group (4) EB-treated rats received EB, Group (5) EB-treated rats received O3, Group (6) EB-treated rats received methylprednisolone (MP), and Group (7) EB-treated rats received half the dose of MP concomitant with O3. EB-treated rats showed a significant increase in the number of footfalls in the grid walk test, decreased brain GSH, and paraoxonase-1 enzyme activity, whereas brain MDA, TNF-α, IL-1β, INF-γ, Cox-2 immunoreactivity, and p53 protein levels were increased. A significant decline in brain serotonin, dopamine, norepinephrine, and MBP immunoreactivity was also reported. Significant improvement of the above-mentioned parameters was demonstrated with the administration of either MP or O3, whereas best amelioration was achieved by combining half the dose of MP with ozone.

  9. TREM2 regulates microglial cell activation in response to demyelination in vivo

    PubMed Central

    Cantoni, Claudia; Bollman, Bryan; Licastro, Danilo; Xie, Mingqiang; Mikesell, Robert; Schmidt, Robert; Yuede, Carla M.; Galimberti, Daniela; Olivecrona, Gunilla; Klein, Robyn S.; Cross, Anne H.; Otero, Karel; Piccio, Laura

    2015-01-01

    Microglia are phagocytic cells that survey the brain and perform neuroprotective functions in response to tissue damage, but their activating receptors are largely unknown. Triggering receptor expressed on myeloid cells 2 (TREM2) is a microglial immunoreceptor whose loss-of-function mutations in humans cause presenile dementia, while genetic variants are associated with increased risk of neurodegenerative diseases. In myeloid cells, TREM2 has been involved in the regulation of phagocytosis, cell proliferation and inflammatory responses in vitro. However, it is unknown how TREM2 contributes to microglia function in vivo. Here, we identify a critical role for TREM2 in the activation and function of microglia during cuprizone (CPZ)-induced demyelination. TREM2-deficient (TREM2−/−) mice had defective clearance of myelin debris and more axonal pathology, resulting in impaired clinical performances compared to wild-type (WT) mice. TREM2−/− microglia proliferated less in areas of demyelination and were less activated, displaying a more resting morphology and decreased expression of the activation markers MHC II and inducible nitric oxide synthase as compared to WT. Mechanistically, gene expression and ultrastructural analysis of microglia suggested a defect in myelin degradation and phagosome processing during CPZ intoxication in TREM2−/− microglia. These findings place TREM2 as a key regulator of microglia activation in vivo in response to tissue damage. PMID:25631124

  10. A Mutation in PMP2 Causes Dominant Demyelinating Charcot-Marie-Tooth Neuropathy

    PubMed Central

    Hyun, Young Se; Kwak, Geon; Choi, Yu-Ri; Yeo, Ha Kyung; Jwa, Dong Hwan; Kim, Eun Ja; Mo, Won Min; Nam, Soo Hyun; Kim, Sung Min; Yoo, Jeong Hyun; Koo, Heasoo; Park, Hwan Tae; Chung, Ki Wha; Choi, Byung-Ok

    2016-01-01

    Charcot-Marie-Tooth disease (CMT) is a heterogeneous group of peripheral neuropathies with diverse genetic causes. In this study, we identified p.I43N mutation in PMP2 from a family exhibiting autosomal dominant demyelinating CMT neuropathy by whole exome sequencing and characterized the clinical features. The age at onset was the first to second decades and muscle atrophy started in the distal portion of the leg. Predominant fatty replacement in the anterior and lateral compartment was similar to that in CMT1A caused by PMP22 duplication. Sural nerve biopsy showed onion bulbs and degenerating fibers with various myelin abnormalities. The relevance of PMP2 mutation as a genetic cause of dominant CMT1 was assessed using transgenic mouse models. Transgenic mice expressing wild type or mutant (p.I43N) PMP2 exhibited abnormal motor function. Electrophysiological data revealed that both mice had reduced motor nerve conduction velocities (MNCV). Electron microscopy revealed that demyelinating fibers and internodal lengths were shortened in both transgenic mice. These data imply that overexpression of wild type as well as mutant PMP2 also causes the CMT1 phenotype, which has been documented in the PMP22. This report might expand the genetic and clinical features of CMT and a further mechanism study will enhance our understanding of PMP2-associated peripheral neuropathy. PMID:26828946

  11. [A clinical case of demyelinating disease with basilar impression].

    PubMed

    Gasparini, A; Sterlicchio, M; Castiglioni, E; Raimondi, E

    1994-11-01

    The authors report a clinical case of a 48-year-old female patient admitted to the Neurological Division following acute symptoms characterised by generalised asthenia, motory disorders (incoordination, equilibrium or gait deficit) accompanied by diplopia. Instrumental (medullary and encephalic NMR) and laboratory tests revealed a malformation of the atlo-occpital hinge with basilar impression and areas of corticosubcortical demyelinisation signifying multiple sclerosis. The liquor test was also positive for the presence of oligoclonal bands of IgG with a Link index of 0.97 (lower v.n. at 0.7). The association between these two pathologies is rare, whereas the need for a differential diagnosis between them often arises. Therefore, two pathologies which are mutually exclusive in many cases were present in an associated form in this case.

  12. Treatment of pediatric chronic inflammatory demyelinating polyneuropathy: Challenges, controversies and questions.

    PubMed

    Desai, Jay; Ramos-Platt, Leigh; Mitchell, Wendy G

    2015-01-01

    Pediatric chronic inflammatory demyelinating polyneuropathy (CIDP) is an uncommon acquired disorder of unknown cause, presumed to have an immunological basis. We report 20 patients seen at Children's Hospital Los Angeles over a period of 10 years. The outcome of our patients was favorable in a vast majority with good response to various treatments instituted. However, residual neurologic deficit was common. The choice of treatment modality was empirical and selected by the treating neurologist. Intravenous immunoglobulin (IVIG) and corticosteroids were most commonly utilized for treatment. Plasmapheresis, mycophenolate mofetil, rituximab, cyclophosphamide, azathioprine, and abatacept were added if the patients were refractory to IVIG or became corticosteroid dependent. The spectrum of disease severity ranged from a single monophasic episode, to multiphasic with infrequent relapses with good response to IVIG, to progressive disease refractory to multiple therapies.

  13. Intravenous immunoglobulin inhibits BAFF production in chronic inflammatory demyelinating polyneuropathy - a new mechanism of action?

    PubMed

    Bick, Sandra; Tschernatsch, Marlene; Karg, Anne; Fuehlhuber, Verena; Trenczek, Tina E; Faltermeier, Kathrin; Hackstein, Holger; Kaps, Manfred; Blaes, Franz

    2013-03-15

    Chronic-inflammatory demyelinating polyneuropathy (CIDP) is an immune-mediated disease treated with intravenous immunoglobulin (IVIg). The underlying mechanism of action remains incompletely understood. The B-cell activating factor BAFF contributes to B-cell homeostasis and (auto-)antibody production. BAFF was recently identified as one key molecule in the development of autoimmune diseases. Herein, we demonstrate that BAFF serum levels are elevated in CIDP patients. IVIg treatment resulted in a significant decrease of BAFF serum level. In vitro, IVIg inhibited BAFF in monocytes. Consequently, we identified BAFF as a new target for IVIg in CIDP treatment and provide a new, Fcγ-receptor independent, mechanism of action for IVIg.

  14. POEMS Syndrome in a Juvenile Initially Diagnosed as Treatment Resistant Chronic Inflammatory Demyelinating Polyneuropathy.

    PubMed

    Krish, Sonia N; Nguyen, Thy; Biliciler, Suur; Kumaravel, Manickam; Wahed, Amer; Risin, Semyon; Sheikh, Kazim A

    2015-12-01

    POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes) is a disorder that mainly affects adults. We report a pediatric patient, initially considered to have Guillain-Barré syndrome, who continued to have progression of neuropathic disease leading to the diagnosis of chronic inflammatory demyelinating polyneuropathy. Diagnosis of POEMS was established by an abnormal bone marrow biopsy, prompted by laboratory and imaging findings, which became abnormal later in the course of the disease. POEMS syndrome is extremely rare in children, and neuropathic features in this age group have not been previously described. This case illustrates that "Guillain-Barré syndrome-like" initial presentation for POEMS, which has not been previously reported. It also emphasizes that in children with progressive acquired neuropathies that are treatment unresponsive, POEMS syndrome should be considered.

  15. Multiple Myeloma Associated Chronic Inflammatory Demyelinating Polyradiculoneuropathy: The Importance of Continued Surveillance

    PubMed Central

    Loncharich, Michael F; Gandhi, Viral; Rana, Sandeep; Balaan, Marvin

    2016-01-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an autoimmune disease presenting with weakness and numbness in a remitting or chronic progressive course. It is known to have several clinical presentations and several associated diseases. CIDP has been associated with multiple myeloma, monoclonal gammopathy of undetermined significance (MGUS), and other paraproteinemias. We present a case of refractory CIDP in which the initial workup for multiple myeloma was negative, and multiple myeloma was then diagnosed two and half years later. Treatment of the multiple myeloma led to clinical improvement. This case is instructive in that perhaps more frequent surveillance for paraproteinemia in patients with CIPD, even after a negative initial workup, could lead to a better clinical outcome. PMID:28070468

  16. Transplanted miR-219-overexpressing oligodendrocyte precursor cells promoted remyelination and improved functional recovery in a chronic demyelinated model.

    PubMed

    Fan, Hong-Bin; Chen, Li-Xia; Qu, Xue-Bin; Ren, Chuan-Lu; Wu, Xiu-Xiang; Dong, Fu-Xing; Zhang, Bao-Le; Gao, Dian-Shuai; Yao, Rui-Qin

    2017-02-01

    Oligodendrocyte precursor cells (OPCs) have the ability to repair demyelinated lesions by maturing into myelin-producing oligodendrocytes. Recent evidence suggests that miR-219 helps regulate the differentiation of OPCs into oligodendrocytes. We performed oligodendrocyte differentiation studies using miR-219-overexpressing mouse embryonic stem cells (miR219-mESCs). The self-renewal and multiple differentiation properties of miR219-mESCs were analyzed by the expression of the stage-specific cell markers Nanog, Oct4, nestin, musashi1, GFAP, Tuj1 and O4. MiR-219 accelerated the differentiation of mESC-derived neural precursor cells (NPCs) into OPCs. We further transplanted OPCs derived from miR219-mESCs (miR219-OPCs) into cuprizone-induced chronically demyelinated mice to observe remyelination, which resulted in well-contained oligodendrocyte grafts that migrated along the corpus callosum and matured to express myelin basic protein (MBP). Ultrastructural studies further confirmed the presence of new myelin sheaths. Improved cognitive function in these mice was confirmed by behavioral tests. Importantly, the transplanted miR219-OPCs induced the proliferation of endogenous NPCs. In conclusion, these data demonstrate that miR-219 rapidly transforms mESCs into oligodendrocyte lineage cells and that the transplantation of miR219-OPCs not only promotes remyelination and improves cognitive function but also enhances the proliferation of host endogenous NPCs following chronic demyelination. These results support the potential of a therapeutic role for miR-219 in demyelinating diseases.

  17. Transplanted miR-219-overexpressing oligodendrocyte precursor cells promoted remyelination and improved functional recovery in a chronic demyelinated model

    PubMed Central

    Fan, Hong-Bin; Chen, Li-Xia; Qu, Xue-Bin; Ren, Chuan-Lu; Wu, Xiu-Xiang; Dong, Fu-Xing; Zhang, Bao-Le; Gao, Dian-Shuai; Yao, Rui-Qin

    2017-01-01

    Oligodendrocyte precursor cells (OPCs) have the ability to repair demyelinated lesions by maturing into myelin-producing oligodendrocytes. Recent evidence suggests that miR-219 helps regulate the differentiation of OPCs into oligodendrocytes. We performed oligodendrocyte differentiation studies using miR-219-overexpressing mouse embryonic stem cells (miR219-mESCs). The self-renewal and multiple differentiation properties of miR219-mESCs were analyzed by the expression of the stage-specific cell markers Nanog, Oct4, nestin, musashi1, GFAP, Tuj1 and O4. MiR-219 accelerated the differentiation of mESC-derived neural precursor cells (NPCs) into OPCs. We further transplanted OPCs derived from miR219-mESCs (miR219-OPCs) into cuprizone-induced chronically demyelinated mice to observe remyelination, which resulted in well-contained oligodendrocyte grafts that migrated along the corpus callosum and matured to express myelin basic protein (MBP). Ultrastructural studies further confirmed the presence of new myelin sheaths. Improved cognitive function in these mice was confirmed by behavioral tests. Importantly, the transplanted miR219-OPCs induced the proliferation of endogenous NPCs. In conclusion, these data demonstrate that miR-219 rapidly transforms mESCs into oligodendrocyte lineage cells and that the transplantation of miR219-OPCs not only promotes remyelination and improves cognitive function but also enhances the proliferation of host endogenous NPCs following chronic demyelination. These results support the potential of a therapeutic role for miR-219 in demyelinating diseases. PMID:28145507

  18. Genetic inactivation of PERK signaling in mouse oligodendrocytes: normal developmental myelination with increased susceptibility to inflammatory demyelination.

    PubMed

    Hussien, Yassir; Cavener, Douglas R; Popko, Brian

    2014-05-01

    The immune-mediated central nervous system (CNS) demyelinating disorder multiple sclerosis (MS) is the most common neurological disease in young adults. One important goal of MS research is to identify strategies that will preserve oligodendrocytes (OLs) in MS lesions. During active myelination and remyelination, OLs synthesize large quantities of membrane proteins in the endoplasmic reticulum (ER), which may result in ER stress. During ER stress, pancreatic ER kinase (PERK) phosphorylates eukaryotic translation initiation factor 2α (elF2α), which activates the integrated stress response (ISR), resulting in a stress-resistant state. Previous studies have shown that PERK activity is increased in OLs within the demyelinating lesions of experimental autoimmune encephalomyelitis (EAE), a model of MS. Moreover, our laboratory has shown that PERK protects OLs from the adverse effects of interferon-γ, a key mediator of the CNS inflammatory response. Here, we have examined the role of PERK signaling in OLs during development and in response to EAE. We generated OL-specific PERK knockout (OL-PERK(ko/ko) ) mice that exhibited a lower level of phosphorylated elF2α in the CNS, indicating that the ISR is impaired in the OLs of these mice. Unexpectedly, OL-PERK(ko/ko) mice develop normally and show no myelination defects. Nevertheless, EAE is exacerbated in these mice, which is correlated with increased OL loss, demyelination, and axonal degeneration. These data indicate that although not needed for developmental myelination, PERK signaling provides protection to OLs against inflammatory demyelination and suggest that the ISR in OLs could be a valuable target for future MS therapeutics.

  19. Chronic inflammatory demyelinating polyneuropathy in common variable immunodeficiency.

    PubMed

    Özdemir, Özlem; Okan, Mehmet S; Kilic, Sara S

    2012-04-01

    Common variable immunodeficiency comprises a heterogeneous group of primary antibody deficiencies with complex clinical and immunologic phenotypes. Immune dysregulation leads to the generation of multiple autoantibodies against various antigenic targets in patients with common variable immunodeficiency. Chronic inflammatory demyelinating polyneuropathy is a heterogeneous disorder that indicates an autoimmune response against peripheral nerve myelin. We describe a 7-year-old girl with common variable immunodeficiency who developed chronic inflammatory polyneuropathy. A 5-day course of intravenous immunoglobulin (500 mg/kg/day) improved her neurologic disorder. Chronic inflammatory demyelinating polyneuropathy should be added to the broadening spectrum of neurologic complications in common variable immunodeficiency. Early detection and consequent treatment may reverse the neurologic sequelae.

  20. Fibrillary glomerulonephritis combined with chronic inflammatory demyelinating polyneuropathy

    PubMed Central

    Sung, Woo Kyung; Jeong, Jin Uk; Bang, Ki Tae; Shin, Jong Ho; Yoo, Ji Hyung; Kim, Nak Min; Park, Jun Hyung; Kim, Joo Heon

    2015-01-01

    A 58-yr-old man presented with leg edema and subacute weakness of his bilateral lower extremities. Urinary and serum immunoelectrophoresis revealed the presence of lambda-type Bence Jones proteins. He was ultimately diagnosed with monoclonal gammopathy of undetermined significance (MGUS). A renal biopsy specimen showed fibrillary glomerulonephritis (FGN), which was randomly arranged as 12–20 m nonbranching fibrils in the basement membranes. Immunofluorescence studies were negative for immunoglobulin (Ig)G, IgM, IgA, C3, and kappa light chains in the capillary walls and mesangial areas. A Congo red stain for amyloid was negative. Electromyography and nerve conduction velocity examinations results were compatible with the presence of demyelinating polyneuropathy. This case showed a rare combination of FGN, without Ig deposition, and MGUS combined with chronic inflammatory demyelinating polyneuropathy (CIDP). PMID:26484033

  1. A Case of Osmotic Demyelination Presenting with Severe Hypernatremia

    PubMed Central

    Han, Min Jee; Kim, Do Hyoung; Kim, Young Hwa; Yang, In Mo; Park, Joon Hyung

    2015-01-01

    Osmotic demyelination syndrome is a demyelinating disorder associated with rapid correction of hyponatremia. But, it rarely occurs in acute hypernatremia, and it leads to permanent neurologic symptoms and is associated with high mortality. A 44-year-old woman treated with alternative medicine was admitted with a history of drowsy mental status. Severe hypernatremia (197mEq/L) with hyperosmolality (415mOsm/kgH2O) was evident initially and magnetic resonance imaging revealed a high signal intensity lesion in the pons, consistent with central pontine myelinolysis. She was treated with 0.45% saline and 5% dextrose water and intravenous corticosteroids. Serum sodium normalized and her clinical course gradually improved. Brain lesion of myelinolysis also improved in a follow-up imaging study. This is the first report of a successful treatment of hypernatremia caused by iatrogenic salt intake, and it confirms the importance of adequate fluid supplementation in severe hypernatremia. PMID:26240598

  2. Isolated paroxysmal dysarthria caused by a single demyelinating midbrain lesion.

    PubMed

    Codeluppi, Luca; Bigliardi, Guido; Chiari, Annalisa; Meletti, Stefano

    2013-10-16

    Paroxysmal dysarthria is an unusual condition characterised by brief episodes of dysarthria with the sudden onset and frequent recurrence. It has been mainly reported in multiple sclerosis and an association with midbrain lesions has been claimed; however, most of the reported patients had multiple brain alterations so it was difficult to associate this symptom with a specific lesion site. We illustrate the cases of two patients with an isolated demyelinating midbrain lesion presenting paroxysmal dysarthria as the only symptom; both participants had oligoclonal bands in the cerebrospinal fluid and an unremarkable follow-up. Both patients had benefit from carbamazepine treatment, similarly to previously reported cases. Our report confirms that a demyelinating midbrain lesion is sufficient to provoke paroxysmal dysarthria. It is noteworthy that an erroneous diagnosis of psychogenic disorders was initially made in both cases, highlighting the importance not to underestimate isolated paroxysmal symptoms in clinical practice.

  3. Orthostatic intolerance in multifocal acquired demyelinating sensory and motor neuropathy.

    PubMed

    Tramontozzi, Louis A; Russell, James A

    2012-09-01

    We report a patient with orthostatic intolerance and syncope as a major clinical manifestation of an acquired multifocal neuropathy with the clinical, electrodiagnostic, and cerebrospinal fluid features of multifocal acquired demyelinating sensory and motor neuropathy or the Lewis-Sumner syndrome. Immunomodulatory therapy led to clinical remission of both somatic and autonomic signs and symptoms. We are unaware of a previous description of symptomatic dysautonomia in this disorder.

  4. Childhood chronic inflammatory demyelinating polyneuropathy with nonuniform pathologic features.

    PubMed

    Luan, Xinghua; Zheng, Riliang; Chen, Bin; Yuan, Yun

    2010-08-01

    Nonuniform pathologic changes in chronic inflammatory demyelinating polyneuropathy were previously reported only in adult humans. We analyzed the pathologic features of 12 children, aged 2-17 years, with chronic inflammatory demyelinating polyneuropathy. Six patients manifested a preceding illness. Five patients presented a chronic, monophasic course, and seven presented a relapsing-remitting course. Three patients exhibited multiple cranial-nerve involvement. Five of 12 (41.7%) patients presented nonuniform features. Two subtypes of nonuniform lesions were revealed. One exhibited varying myelinated fiber content between nerve fascicles, and one exhibited onion bulbs involving a variable number of fascicles. Macrophages were evident in 11 patients, and the number of CD3-positive T cells in the nonuniform group was greater compared with the uniform group (P = 0.045). Our results demonstrate that childhood chronic inflammatory demyelinating polyneuropathy exhibits pathologically nonuniform features, thus providing more evidence to assist in differential diagnoses of pediatric patients. However, clinical and electrophysiologic features, as well as responses to treatment, were similar in the nonuniform and uniform groups.

  5. Are electrophysiological criteria useful in distinguishing childhood demyelinating neuropathies?

    PubMed

    Potulska-Chromik, Anna; Ryniewicz, Barbara; Aragon-Gawinska, Karolina; Kabzinska, Dagmara; Seroka, Andrzej; Lipowska, Marta; Kaminska, Anna M; Kostera-Pruszczyk, Anna

    2016-03-01

    Childhood chronic inflammatory demyelinating polyneuropathy (CIDP) needs to be differentiated from hereditary neuropathy. We aimed to validate existing CIDP nerve conduction study (NCS) criteria in a group of children with demyelinating neuropathies of chronic or subacute onset. Retrospective analysis of clinical and NCS results in 18 children with CIDP, 7 with hereditary neuropathy with pressure palsy (HNPP), and 24 with Charcot-Marie-Tooth 1a (CMT1a). AAN and EFNS electrodiagnostic CIDP criteria were fulfilled in 17 of 18 CIDP, 3 of 7 HNPP, and 23 of 24 CMT1a patients. A distal compound muscle action potential (dCMAP) of >9 ms was observed in 14 of 18 CIDP patients but not in any patients with HNPP. Abnormal median/normal sural SNAP (AMNS) and a 10 m/s difference between conduction velocities (CV) of two corresponding nerves were not observed in any CMT1a patients. NCS in CMT1a, HNPP, and CIDP reflect demyelination. dCMAP duration, sensory AMNS, and a 10 m/s CV difference parameter are most useful in the differential diagnosis of pediatric CIDP.

  6. Systematic reviews of treatment for inflammatory demyelinating neuropathy*

    PubMed Central

    Hughes, RAC

    2002-01-01

    This review describes the progress made in preparing Cochrane systematic reviews of randomized controlled trials for Guillain–Barré syndrome (GBS), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), multifocal motor neuropathy (MMN) and the demyelinating neuropathies associated with paraproteins. The discovery of antibodies against myelin andaxolemmal glycolipids and proteins has not yet replaced the clinicopathological classificationon which treatment trials have been based. Systematic reviews have endorsed the equivalence of plasma exchange (PE) and intravenous immunoglobulin (IVIg) and the lack of efficacy of steroids in GBS. Systematic reviews have also endorsed the value of steroids, PE and IVIg in CIDP butrandomized controlled trials have only shown benefit from IVIg in MMN. There is a paucity of evidence concerning the efficacy of treatments in paraproteinaemic demyelinating neuropathy apartment from small trials showing short-term benefit from PE or IVIg. There is a lack of good quality controlled trials of immunosuppressive agents in any of these conditions. As the numberof treatment trials increases, Cochrane systematic reviews will be an increasingly valuable resource for summarizing the evidence from randomised controlled trials on which to base clinical practice. They already demonstrate major deficiencies in the existing evidence base. PMID:12090400

  7. Time-dependent changes in proinflammatory and neurotrophic responses of microglia and astrocytes in a rat model of osmotic demyelination syndrome.

    PubMed

    Iwama, Shintaro; Sugimura, Yoshihisa; Suzuki, Haruyuki; Suzuki, Hiromi; Murase, Takashi; Ozaki, Nobuaki; Nagasaki, Hiroshi; Arima, Hiroshi; Murata, Yoshiharu; Sawada, Makoto; Oiso, Yutaka

    2011-03-01

    Osmotic demyelination syndrome (ODS) is a serious demyelinating disease in the central nervous system usually caused by rapid correction of hyponatremia. In an animal model of ODS, we previously reported microglial accumulation expressing proinflammatory cytokines. Microglia and astrocytes secreting proinflammatory cytokines and neurotrophic factors are reported to be involved in the pathogenesis of demyelinative diseases. Therefore, to clarify the role of microglial and astrocytic function in ODS, we examined the time-dependent changes in distribution, morphology, proliferation, and mRNA/protein expression of proinflammatory cytokines, neurotrophic factors, and matrix metalloproteinase (MMP) in microglia and astrocytes 2 days (early phase) and 5 days (late phase) after the rapid correction of hyponatremia in ODS rats. The number of microglia time dependently increased at demyelinative lesion sites, proliferated, and expressed tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, inducible nitric oxide synthase, and MMP2, 9, and 12 at the early phase. Microglia also expressed leukemia inhibitory factor (a neurotrophic factor) and phagocytosed myelin debris at the late phase. The number of astrocytes time dependently increased around demyelinative lesions, extended processes to lesions, proliferated, and expressed nerve growth factor and glial cell line-derived neurotrophic factor at the late phase. Moreover, treatment with infliximab, a monoclonal antibody against TNF-α, significantly attenuated neurological impairments. Our results suggest that the role of microglia in ODS is time dependently shifted from detrimental to protective and that astrocytes play a protective role at the late phase. Modulation of excessive proinflammatory responses in microglia during the early phase after rapid correction may represent a therapeutic target for ODS.

  8. Absence of CCL2 and CCL3 Ameliorates Central Nervous System Grey Matter But Not White Matter Demyelination in the Presence of an Intact Blood-Brain Barrier.

    PubMed

    Janssen, Katharina; Rickert, Mira; Clarner, Tim; Beyer, Cordian; Kipp, Markus

    2016-04-01

    A broad spectrum of diseases is characterized by myelin abnormalities, oligodendrocyte pathology, and concomitant glia activation, among multiple sclerosis (MS). Our knowledge regarding the factors triggering gliosis and demyelination is scanty. Chemokines are pivotal for microglia and astrocyte activation and orchestrate critical steps during the formation of central nervous system (CNS) demyelinating lesions. Redundant functions of chemokines complicate, however, the study of their functional relevance. We used the cuprizone model to study redundant functions of two chemokines, CCL2/MCP1 and CCL3/MIP1α, which are critically involved in the pathological process of cuprizone-induced demyelination. First, we generated a mutant mouse strain lacking functional genes of both chemokines and demonstrated that double-mutant animals are viable, fertile, and do not present with gross abnormalities. Astrocytes and peritoneal macrophages, cultured form tissues of these animals did neither express CCL2 nor CCL3. Exposure to cuprizone resulted in increased CCL2 and CCL3 brain levels in wild-type but not mutant animals. Cuprizone-induced demyelination, oligodendrocyte loss, and astrogliosis were significantly ameliorated in the cortex but not corpus callosum of chemokine-deficient animals. In summary, we provide a novel powerful model to study the redundant function of two important chemokines. Our study reveals that chemokine function in the CNS redounds to region-specific pathophysiological events.

  9. The Effect of Stereotactic Injections on Demyelination and Remyelination: a Study in the Cuprizone Model.

    PubMed

    Tejedor, Laura Salinas; Wostradowski, Tanja; Gingele, Stefan; Skripuletz, Thomas; Gudi, Viktoria; Stangel, Martin

    2017-01-26

    Remyelination is the natural repair mechanism in demyelinating disorders of the central nervous system (CNS) such as multiple sclerosis. Several animal models have been used to study demyelination and remyelination. Among toxic animal models, oral administration of the toxin cuprizone leads to white and gray matter demyelination. In contrast, focal demyelination models include the stereotactic application of a toxin such as lysolecithin or ethidium bromide. The injection procedure generates a local disruption of the blood-brain barrier (BBB) and might thus trigger a local inflammatory reaction and consequently may influence demyelination and remyelination. In order to study such consequences, we applied stereotactic injections in the cuprizone model where demyelination and remyelination are mediated independent of this procedure. Immunohistochemistry was performed to detect the presence of lymphocytes and activated glial cells in the injection area. Blood protein stainings were used to assess the integrity of the BBB and myelin staining to evaluate demyelination and remyelination processes. Stereotactic injection led to a local disruption of the BBB as shown by local extravasation of blood proteins. Along the injection canal, T and B lymphocytes could be detected and there was a tendency of a higher microgliosis and astrocytosis. However, these changes did not influence demyelination and remyelination processes at the site of injection, in the corpus callosum, or in the cerebral cortex. Our results suggest that a local stereotactic injection has no major impact on CNS demyelination and remyelination.

  10. Transient auditory nerve demyelination as a new mechanism for hidden hearing loss

    PubMed Central

    Wan, Guoqiang; Corfas, Gabriel

    2017-01-01

    Hidden hearing loss (HHL) is a recently described auditory neuropathy believed to contribute to speech discrimination and intelligibility deficits in people with normal audiological tests. Animals and humans with HHL have normal auditory thresholds but defective cochlear neurotransmission, that is, reduced suprathreshold amplitude of the sound-evoked auditory nerve compound action potential. Currently, the only cellular mechanism known for HHL is loss of inner hair cell synapses (synaptopathy). Here we report that transient loss of cochlear Schwann cells results in permanent auditory deficits characteristic of HHL. This auditory neuropathy is not associated with synaptic loss, but rather with disruption of the first heminodes at the auditory nerve peripheral terminal. Thus, this study identifies a new mechanism for HHL, highlights the long-term consequences of transient Schwann cell loss on hearing and might provide insights into the causes of the auditory deficits reported in patients that recover from acute demyelinating diseases such as Guillain–Barré syndrome. PMID:28211470

  11. Probiotics Lactobacillus plantarum and bifidobacterium B94: cognitive function in demyelinated model

    PubMed Central

    Goudarzvand, Mahdi; Rasouli koohi, Samira; Khodaii, Zohreh; Soleymanzadeh Moghadam, Somayeh

    2016-01-01

    Background: Multiple Sclerosis (MS) is a disease of the immune system that creates damage of Learning and memory in that. Using probiotic supplements is recommended for preventing MS disease and improving memory. This study aimed to investigate the effect of Lactobacillus plantarum (LP) and bifidobacterium B94 (BB94), on acquisition phase of spatial memory in the local demyelination of rats` hippocampus. Methods: In this study, 32 male Wistar rats were divided into control, damage group and treatment groups. Treatment groups were including (LP) and (BB94). After the induction of demyelination by 3 μl of EB into the right dentate gyrus of the hippocampus in treatment groups, 1.5×108 probiotic bacteria were administered by gavage for 28 days. Data was analyzed using one-way ANOVA and Tukey post-hoc tests (p≤0.05). Results: Findings demonstrated that injection of EB caused a significant increase in traveled distance (p<0.01) and also escape latency (p<0.05) compared with control group. Also, effect administrations of (LP) and (BB94) on traveled distance and escape latency were reviewed, and it was determined that administration of them do not cause significant reduction in the traveled distance compared with the lesion group. Also mentioned probiotics has no significant effect on swimming speed compared with lesion and saline groups. Conclusion: According to some studies, probiotics have a positive impact on improving the performance of spatial memory and learning, although the results of the current study could not indicate finality of this assumption. It seems that more researches is needed on this subject. PMID:27579282

  12. Multiple giant angiokeratoma of Fordyce on the shaft of the penis masquerading as keratoacanthoma*

    PubMed Central

    Ghosh, Sudip Kumar; Ghosh, Shouvik; Agarwal, Megha

    2015-01-01

    The term 'angiokeratoma' includes a wide range of dermatological conditions of hyperkeratotic vascular disorders with a similar histologic combination of hyperkeratosis and superficial dermal vascular ectasia. Angiokeratomas can be classified into localized and systemic forms. Angiokeratoma of Fordyce (AKF) is a localized form of angiokeratoma, clinically characterized by 1- to 6-mm, black, blue, or dark red, dome-shaped papules located on the scrotum, shaft of penis, labia majora, clitoris, inner thigh, and lower abdomen. We describe herein a case of giant angiokeratoma of Fordyce on shaft of the penis in an elderly man, clinically masquerading as keratoacanthoma. PMID:26312700

  13. Autoantibodies against vinculin in patients with chronic inflammatory demyelinating polyneuropathy.

    PubMed

    Beppu, Minako; Sawai, Setsu; Satoh, Mamoru; Mori, Masahiro; Kazami, Takahiro; Misawa, Sonoko; Shibuya, Kazumoto; Ishibashi, Masumi; Sogawa, Kazuyuki; Kado, Sayaka; Kodera, Yoshio; Nomura, Fumio; Kuwabara, Satoshi

    2015-10-15

    To identify the target molecules of chronic inflammatory demyelinating polyneuropathy (CIDP), we used proteomic-based approach in the extracted proteins from porcine cauda equina. Two of 31 CIDP patients had markedly elevated serum autoantibodies against vinculin, a cell adhesion protein. Both of the patients with anti-vinculin antibodies had similar clinical manifestation, which are compatible with those of "typical" CIDP. Immunocytochemistry showed that vinculin was stained at the myelin sheath of the sciatic nerves by serum samples. Our results suggest that vinculin is a possible immunological target molecule in a subpopulation of typical CIDP patients.

  14. Chronic inflammatory demyelinating polyneuropathy after treatment with interferon-alpha.

    PubMed

    Hirotani, Makoto; Nakano, Hitoshi; Ura, Shigehisa; Yoshida, Kazuto; Niino, Masaaki; Yabe, Ichiro; Sasaki, Hidenao

    2009-01-01

    Interferon-alpha (IFN-alpha), though widely used for the treatment of chronic viral hepatitis, may be associated with the occurrence of autoimmune disorders. In this case report, a patient with chronic hepatitis C virus infection had chronic inflammatory demyelinating polyneuropathy (CIDP) after the initiation of IFN-alpha therapy. The neurological symptoms of this patient continued to progress even though the treatment with IFN-alpha had been withdrawn; the symptoms improved dramatically following treatment with intravenous immunoglobulin. This case may therefore provide an important clue to understand the immune mechanism of CIDP and IFN-alpha.

  15. Demyelinating Peripheral Neuropathy Due to Renal Cell Carcinoma

    PubMed Central

    Nishioka, Kenya; Fujimaki, Motoki; Kanai, Kazuaki; Ishiguro, Yuta; Nakazato, Tomoko; Tanaka, Ryota; Yokoyama, Kazumasa; Hattori, Nobutaka

    2017-01-01

    Renal cell carcinoma (RCC) patients who develop a paraneoplastic syndrome may present with neuromuscular disorders. We herein report the case of a 50-year-old man who suffered from progressive gait disturbance and muscle weakness. The results of a nerve conduction study fulfilled the criteria of chronic inflammatory demyelinating polyneuropathy. An abdominal CT scan detected RCC, the pathological diagnosis of which was clear cell type. After tumor resection and a single course of intravenous immunoglobulin therapy, the patient's symptoms drastically improved over the course of one year. The patient's neurological symptoms preceded the detection of cancer. A proper diagnosis and the initiation of suitable therapies resulted in a favorable outcome. PMID:28049985

  16. Reconstruction magnetic resonance neurography in chronic inflammatory demyelinating polyneuropathy.

    PubMed

    Shibuya, Kazumoto; Sugiyama, Atsuhiko; Ito, Sho-ichi; Misawa, Sonoko; Sekiguchi, Yukari; Mitsuma, Satsuki; Iwai, Yuta; Watanabe, Keisuke; Shimada, Hitoshi; Kawaguchi, Hiroshi; Suhara, Tetsuya; Yokota, Hajime; Matsumoto, Hiroshi; Kuwabara, Satoshi

    2015-02-01

    To study distribution and patterns of nerve hypertrophy in chronic inflammatory demyelinating polyneuropathy (CIDP), magnetic resonance neurography with 3-dimensional reconstruction of short tau inversion recovery images was performed in 33 patients. This technique clearly showed longitudinal morphological changes from the cervical roots to the nerve trunks in the proximal arm. Nerve enlargement was detected in 88% of the patients. According to the clinical subtype of CIDP, typical CIDP patients showed symmetric and root-dominant hypertrophy, whereas Lewis-Sumner syndrome patients had multifocal fusiform hypertrophy in the nerve trunks. The patterns of nerve hypertrophy presumably reflect the different pathophysiology of each CIDP subtype.

  17. Intrathecal Dexmedetomidine for Anaesthetic Management of a Patient with Chronic Inflammatory Demyelinating Polyneuropathy

    PubMed Central

    Srinivasalu, D

    2016-01-01

    Chronic demyelinating disorders have multifactorial origin but common important physiologic and anaesthetic considerations. Choice of anaesthesia technique and the drugs used, undertanding the pros and cons of using central neuraxial blocks will help in successful management of such patients. We describe the anaesthetic management of a 34-year-old male with chronic inflammatory demyelinating polyneuropathy posted for cystolithotripsy. PMID:27790558

  18. Clostridium perfringens Epsilon Toxin Causes Selective Death of Mature Oligodendrocytes and Central Nervous System Demyelination

    PubMed Central

    Linden, Jennifer R.; Ma, Yinghua; Zhao, Baohua; Harris, Jason Michael; Rumah, Kareem Rashid; Schaeren-Wiemers, Nicole

    2015-01-01

    ABSTRACT Clostridium perfringens epsilon toxin (ε-toxin) is responsible for a devastating multifocal central nervous system (CNS) white matter disease in ruminant animals. The mechanism by which ε-toxin causes white matter damage is poorly understood. In this study, we sought to determine the molecular and cellular mechanisms by which ε-toxin causes pathological changes to white matter. In primary CNS cultures, ε-toxin binds to and kills oligodendrocytes but not astrocytes, microglia, or neurons. In cerebellar organotypic culture, ε-toxin induces demyelination, which occurs in a time- and dose-dependent manner, while preserving neurons, astrocytes, and microglia. ε-Toxin specificity for oligodendrocytes was confirmed using enriched glial culture. Sensitivity to ε-toxin is developmentally regulated, as only mature oligodendrocytes are susceptible to ε-toxin; oligodendrocyte progenitor cells are not. ε-Toxin sensitivity is also dependent on oligodendrocyte expression of the proteolipid myelin and lymphocyte protein (MAL), as MAL-deficient oligodendrocytes are insensitive to ε-toxin. In addition, ε-toxin binding to white matter follows the spatial and temporal pattern of MAL expression. A neutralizing antibody against ε-toxin inhibits oligodendrocyte death and demyelination. This study provides several novel insights into the action of ε-toxin in the CNS. (i) ε-Toxin causes selective oligodendrocyte death while preserving all other neural elements. (ii) ε-Toxin-mediated oligodendrocyte death is a cell autonomous effect. (iii) The effects of ε-toxin on the oligodendrocyte lineage are restricted to mature oligodendrocytes. (iv) Expression of the developmentally regulated proteolipid MAL is required for the cytotoxic effects. (v) The cytotoxic effects of ε-toxin can be abrogated by an ε-toxin neutralizing antibody. PMID:26081637

  19. Vitamin D3 attenuates oxidative stress and cognitive deficits in a model of toxic demyelination

    PubMed Central

    Tarbali, Sepideh; Khezri, Shiva

    2016-01-01

    Objective(s): Multiple sclerosis (MS) is a demyelinating disease. The prevalence of MS is highest where environmental supplies of vitamin D are low. Cognitive deficits have been observed in patients with MS. Oxidative damage may contribute to the formation of MS lesions. Considering the involvement of hippocampus in MS, an attempt is made in this study to investigate the effects of vitamin D3 on behavioral process and the oxidative status in the dorsal hippocampus (CA1 area) following the induction of experimental demyelination in rats. Materials and Methods: Animals were divided into six groups. Control group: animals received no surgery and treatment; saline group: animals received normal saline; sham group: animals received 150 μl sesame oil IP; vitamin D3 group: animals received 5 μg/kg vitamin D3 IP; lysophosphatidyl choline (LPC) group (toxic demyelination’s model): animals received LPC by stereotaxic intra-hippocampal injection of 2 μl LPC in CA1 area; Vitamin D3- treated group: animals were treated with vitamin D3 at doses of 5 μg/kg IP for 7 and 21 days post lesion. The spatial memory, biochemical parameters including catalase (CAT) activities and lipid peroxidation levels were investigated. Results: Animals in LPC group had more deficits in spatial memory than the control group in radial arm maze. Vitamin D3 significantly improved spatial memory compared to LPC group. Also, results indicated that vitamin D3 caused a decrease in lipid peroxidation levels and an increase in CAT activities. Conclusion: Current findings suggest that vitamin D3 may have a protective effect on cognitive deficits and oxidative stress in toxic demyelination’s model. PMID:27096068

  20. Axonal and perikaryal involvement in chronic inflammatory demyelinating polyneuropathy

    PubMed Central

    Nagamatsu, M; Terao, S; Misu, K; Li, M; Hattori, N; Ichimura, M; Sakai, M; Yamamoto, H; Watanabe, H; Riku, S; Ikeda, E; Hata, J; Oda, M; Satake, M; Nakamura, N; Matsuya, S; Hashizume, Y; Sobue, G

    1999-01-01

    OBJECTIVES—To assess the extent of loss of myelinated nerve fibres and spinal motor neuron loss in chronic inflammatory demyelinating polyneuropathy (CIDP), a clinicopathological study was conducted on biopsied sural nerves and necropsied spinal cords from patients with CIDP.
METHODS—The myelinated fibre pathology of 71 biopsied sural nerves and motor neuron pathology of nine necropsied spinal cords at L4 levels in patients with CIDP were quantitatively and immunohistochemically assessed.
RESULTS—Myelinated nerve fibre density was significantly diminished to 65.4% of the control values (p <0.0001), correlating inversely with the extent of segmental demyelination and remyelination (r = −0.43, p < 0.0005) and duration of illness (r = −0.31, p < 0.01). Numbers of large spinal motor neurons in CIDP were variably but significantly diminished (range from 46.0 to 97.6% of the age matched control value (p < 0.005)), and reactive astrogliosis was evident in the ventral horn in CIDP. The frequency of ventral horn neurons exhibiting central chromatolysis and the accumulation of phosphorylated high molecular weight neurofilament protein was significantly higher in CIDP than in controls (p<0.01 and p<0.05).
CONCLUSIONS—The loss of nerve axons and spinal motor neurons is common in CIDP, and extensive in some cases. These neuronal and axonal losses may influence the functional prognosis in CIDP.

 PMID:10329744

  1. Microglial Hv1 proton channel promotes cuprizone-induced demyelination through oxidative damage.

    PubMed

    Liu, Junli; Tian, Daishi; Murugan, Madhuvika; Eyo, Ukpong B; Dreyfus, Cheryl F; Wang, Wei; Wu, Long-Jun

    2015-10-01

    NADPH oxidase (NOX)-dependent reactive oxygen species (ROS) production in inflammatory cells including microglia plays an important role in demyelination and free radical-mediated tissue injury in multiple sclerosis (MS). However, the mechanism underlying microglial ROS production and demyelination remains largely unknown. The voltage-gated proton channel, Hv1, is selectively expressed in microglia and is required for NOX-dependent ROS generation in the brain. In the present study, we sought to determine the role of microglial Hv1 proton channels in a mouse model of cuprizone-induced demyelination, a model for MS. Following cuprizone exposure, wild-type mice presented obvious demyelination, decreased myelin basic protein expression, loss of mature oligodendrocytes, and impaired motor coordination in comparison to mice on a normal chow diet. However, mice lacking Hv1 (Hv1(-/-) ) are partially protected from demyelination and motor deficits compared with those in wild-type mice. These rescued phenotypes in Hv1(-/-) mice in cuprizone-induced demyelination is accompanied by reduced ROS production, ameliorated microglial activation, increased oligodendrocyte progenitor cell (NG2) proliferation, and increased number of mature oligodendrocytes. These results demonstrate that the Hv1 proton channel is required for cuprizone-induced microglial oxidative damage and subsequent demyelination. Our study suggests that the microglial Hv1 proton channel is a unique target for controlling NOX-dependent ROS production in the pathogenesis of MS.

  2. Novel immunotherapeutic strategies in chronic inflammatory demyelinating polyneuropathy.

    PubMed

    Mathis, Stéphane; Vallat, Jean-Michel; Magy, Laurent

    2016-02-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a chronic immune-mediated neuropathy: it is clinically heterogeneous (relapsing-remitting form, chronic progressive form, monophasic form or CIDP having a Guillain-Barré syndrome-like onset), but potentially treatable. Although its pathophysiology remains largely unknown, CIDP is considered an immune-mediated neuropathy. Therefore, many immunotherapies have been proposed in this peripheral nervous system disorder, the most known efficient treatments being intravenous immunoglobulin, corticosteroids and plasma exchange. However, these therapies remain unsatisfactory for many patients, so numerous other immunotherapeutic strategies have been evaluated, based on their immunosuppressant or immunomodulatory potency. We have performed a large review of the literature about treatment in CIDP, with a special emphasis on novel and alternative immunotherapeutic strategies.

  3. [Treatment's initiation in chronic inflammatory demyelinating polyradiculopathy (CIDP)].

    PubMed

    Uzenot, D; Azulay, J-P; Pouget, J

    2007-09-01

    Treatment's initiation in chronic inflammatory demyelinating polyradiculopathy (CIDP) remains a difficult medical decision. Only plasma exchanges, intravenous immunoglobulins (IVIg) and corticosteroids are proven effective treatments. Immunosuppressors are actually not first-line treatments in CIDP. Particular CIDP forms are associated with different response to treatments: pure motor CIDP should be treated by IVIg, and corticosteroids should only carefully be used in Lewis-Sumner syndrome. Otherwise, IVIg are first-line treatment in diabetic patients. Patients must be informed of side's effects and expected clinical effects. Early treatment was actually not proved to prevent axonal damages in CIDP patients, and waiting seems to be the best therapeutic option in poorly symptomatic patients. Recently, clinical guidelines were proposed to help clinician in this treatment choice, but there is no consensus about the best dose, duration or administration way to CIDP treatments. Further studies should be performed to clarify these points and to determine immunosuppressor agents place in treatment strategy.

  4. Intractable chronic inflammatory demyelinating polyneuropathy treated successfully with ciclosporin

    PubMed Central

    Odaka, M; Tatsumoto, M; Susuki, K; Hirata, K; Yuki, N

    2005-01-01

    Background: Chronic inflammatory demyelinating polyneuropathy (CIDP) is a heterogeneous disorder and both clinical course and response to treatment vary widely. Because of the propensity for relapse, CIDP requires maintenance therapy after the initial response to treatment. There is no consensus regarding this in the published literature. Present report: A patient with CIDP was treated with oral prednisolone and cyclophosphamide pulse therapy but required repeated plasma exchange and intravenous immunoglobulin (IVIg). Treatment with ciclosporin freed the patient from repeated IVIg administration. Therapeutic responses in 14 subsequent cases including three patients who showed improvement with ciclosporin are also presented along with an algorithm of the authors' suggested protocol for treatment. Conclusion: Ciclosporin should be considered for patients with intractable CIDP who require repeated IVIg. PMID:16024890

  5. Severe bleeding after antithrombotic therapy in urosepsis masquerading as myocardial infarction.

    PubMed

    Cheng, Kuo-Wei; Shih, Hsin-Chin; How, Chorng-Kuang; Lin, Yang-Ying; Hung-Tsang Yen, David; Huang, Mu-Shun

    2011-01-01

    Cardiac dysfunction is common in patients with severe sepsis and septic shock. We present a 71-year-old woman with Escherichia coli urosepsis and sepsis-induced myocardial injury masquerading as non-ST elevated myocardial ischemia. Spontaneous psoas hematoma requiring blood transfusion and intracranial hemorrhage developed after antiplatelet and anticoagulant therapies, even in therapeutic doses. The patient was managed conservatively and recovered well with minor residual hemiparesis. Bleeding complications are a common risk of antithrombotic therapy. It is therefore crucial to weigh the impact of efficacy against safety. Old age, female gender, renal insufficiency and sepsis character increased the risk of bleeding in this patient. A misinterpretation of elevated cardiac troponin I may give rise to a diagnostic dilemma and cause unnecessary morbidity.

  6. Retained soft contact lens masquerading as a chalazion: a case report.

    PubMed

    Agarwal, Pankaj Kumar; Ahmed, Taha Y; Diaper, Charles J M

    2013-02-01

    A misplaced contact lens is a common ocular emergency presenting to the eye casualty. We report a case of lost soft contact lens which migrated in the lid and presented 13 years later with symptomatic eye lid swelling. Authors in the past have reported migration and subsequent retention of lost hard lenses in locations such as the superior fornix and eyelid. To the best of our knowledge, misplaced soft contact lens masquerading as a chalazion has not been reported in the literature. Consideration should be given to the possibility of a retained contact lens in a patient with a history of a lost or misplaced lens, and examination of the ocular surface with double eversion of the upper lid should be performed.

  7. Thoracic exophytic ependymoma masquerading as a benign extra-axial tumor.

    PubMed

    Chung, Charlotte Y; Koffie, Robert M; Dewitt, John C; Aronson, Joshua P

    2016-11-01

    Spinal tumors are conventionally differentiated based on location in relation to the spinal cord. Benign spinal tumors such as schwannomas and meningiomas are typically extra-axial (intradural extramedullary) lesions, whereas more aggressive primary spinal tumors such as ependymomas are typically intramedullary masses. Rarely, ependymomas can have both intramedullary and extramedullary components (typically referred to as exophytic ependymomas). We report a case of a spinal exophytic ependymoma that radiographically masqueraded as a benign intradural extramedullary lesion causing cord compression and neurologic deficit in a 47-year-old man. The diagnosis of exophytic ependymoma was made intra-operatively, with resultant gross total resection of the extramedullary portion and subtotal resection of the intramedullary portion. Histopathological examination confirmed ependymoma with World Health Organization grade II/IV. Pre-operative suspicion of an exophytic ependymoma influences operative planning and clinical management. We review the literature and discuss clinical management strategies for these interesting spinal tumors.

  8. Retained soft contact lens masquerading as a chalazion: A case report

    PubMed Central

    Agarwal, Pankaj Kumar; Ahmed, Taha Y; Diaper, Charles J M

    2013-01-01

    A misplaced contact lens is a common ocular emergency presenting to the eye casualty. We report a case of lost soft contact lens which migrated in the lid and presented 13 years later with symptomatic eye lid swelling. Authors in the past have reported migration and subsequent retention of lost hard lenses in locations such as the superior fornix and eyelid. To the best of our knowledge, misplaced soft contact lens masquerading as a chalazion has not been reported in the literature. Consideration should be given to the possibility of a retained contact lens in a patient with a history of a lost or misplaced lens, and examination of the ocular surface with double eversion of the upper lid should be performed. PMID:23412528

  9. Sebaceous carcinoma: the great masquerader: emgerging concepts in diagnosis and treatment.

    PubMed

    Buitrago, William; Joseph, Aaron K

    2008-01-01

    Sebaceous carcinoma (SC) is a rare tumor with a high rate of local recurrence and metastasis to lymph nodes and organs. The majority of SCs occur in the periocular region frequently presenting as painless, round subcutaneous nodules with a high tendency of diffuse and invasive growth in the eyelid and conjunctiva. It frequently masquerades as inflammatory conditions or as other tumors leading to delay in diagnosis, inappropriate treatment and increased morbidity and mortality. Sebaceous carcinoma is associated with Muir-Torre syndrome, a genetic condition presenting with sebaceous skin tumors associated with internal malignancy. Therefore, SC patients must be carefully evaluated and referred to an internist or gastroenterologist when indicated. Surgery is the definitive therapy for SC. In recent years, less radical surgical strategies are being used with improved outcomes. Current studies demonstrate that Mohs micrographic surgery (MMS) provides maximal tissue conservation and lower recurrence rates. Greater awareness and understanding of SC and its behavior has led to earlier diagnosis and appropriate treatment.

  10. Adaptive human immunity drives remyelination in a mouse model of demyelination

    PubMed Central

    El Behi, Mohamed; Sanson, Charles; Bachelin, Corinne; Guillot-Noël, Léna; Fransson, Jennifer; Stankoff, Bruno; Maillart, Elisabeth; Sarrazin, Nadège; Guillemot, Vincent; Abdi, Hervé; Cournu-Rebeix, Isabelle; Fontaine, Bertrand

    2017-01-01

    Abstract One major challenge in multiple sclerosis is to understand the cellular and molecular mechanisms leading to disease severity progression. The recently demonstrated correlation between disease severity and remyelination emphasizes the importance of identifying factors leading to a favourable outcome. Why remyelination fails or succeeds in multiple sclerosis patients remains largely unknown, mainly because remyelination has never been studied within a humanized pathological context that would recapitulate major events in plaque formation such as infiltration of inflammatory cells. Therefore, we developed a new paradigm by grafting healthy donor or multiple sclerosis patient lymphocytes in the demyelinated lesion of nude mice spinal cord. We show that lymphocytes play a major role in remyelination whose efficacy is significantly decreased in mice grafted with multiple sclerosis lymphocytes compared to those grafted with healthy donors lymphocytes. Mechanistically, we demonstrated in vitro that lymphocyte-derived mediators influenced differentiation of oligodendrocyte precursor cells through a crosstalk with microglial cells. Among mice grafted with lymphocytes from different patients, we observed diverse remyelination patterns reproducing for the first time the heterogeneity observed in multiple sclerosis patients. Comparing lymphocyte secretory profile from patients exhibiting high and low remyelination ability, we identified novel molecules involved in oligodendrocyte precursor cell differentiation and validated CCL19 as a target to improve remyelination. Specifically, exogenous CCL19 abolished oligodendrocyte precursor cell differentiation observed in patients with high remyelination pattern. Multiple sclerosis lymphocytes exhibit intrinsic capacities to coordinate myelin repair and further investigation on patients with high remyelination capacities will provide new pro-regenerative strategies. PMID:28334918

  11. A spectrum of inflammation and demyelination in acute disseminated encephalomyelitis (ADEM) of children.

    PubMed

    Esposito, Susanna; Di Pietro, Giada Maria; Madini, Barbara; Mastrolia, Maria Vincenza; Rigante, Donato

    2015-10-01

    Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disease of the central nervous system that involves multifocal areas of the white matter, rarely the gray matter and spinal cord, mainly affecting children and mostly occurring 1-2weeks after infections or more rarely after vaccinations. Though a specific etiologic agent is not constantly identified, to evaluate carefully patient's clinical history and obtain adequate samples for the search of a potential ADEM causal agent is crucial. In the case of a prompt diagnosis and adequate treatment, most children with ADEM have a favorable outcome with full recovery, but in the case of diagnostic delays or inappropriate treatment some patients might display neurological sequelae and persistent deficits or even show an evolution to multiple sclerosis. The suspicion of ADEM rises on a clinical basis and derives from systemic and neurologic signs combined with magnetic resonance imaging of the central nervous system. Other advanced imaging techniques may help an appropriate differential diagnosis and definition of exact disease extension. Although there is no standardized protocol or management for ADEM, corticosteroids, intravenous immunoglobulin, and plasmapheresis have been successfully used. There is no marker that permits to identify the subset of children with worse prognosis and future studies should try to detect any biological clue for prevision of neurologic damage as well as should optimize treatment strategies using an approach based on the effective risk of negative evolution.

  12. Neurodegenerative disorder masquerading as psychosis in a forensic psychiatry setting.

    PubMed

    Sommerlad, Andrew; Lee, James; Warren, Jason; Price, Gary

    2014-06-13

    A man presenting in his 50s, following conviction for a non-violent crime, to forensic psychiatric services, and then to a neuropsychiatry service with an unusual presentation of psychosis: second person auditory hallucinations, grandiose delusions and somatic delusions. Detailed collateral and family history revealed a background of progressive cognitive deficit and a family history of motor neuron disease. MRI of the brain revealed asymmetrical parieto-occipital volume loss and genetic testing demonstrated a pathogenic expansion of the chromosome 9 open reading frame 72 (C9ORF72) gene consistent with familial frontotemporal dementia caused by a hexanucleotide repeat expansion at C9ORF72, a recently discovered cause of familial frontotemporal dementia/motor neuron disease. This form of frontotemporal dementia should be considered as an important potential differential diagnosis for patients presenting with psychotic symptoms in later life, in whom a detailed family history and thorough cognitive assessment is essential.

  13. Spontaneous Coronary Dissection Masquerading as Benign Fascicular Ventricular Tachycardia.

    PubMed

    Ho, Sara Wei-Fen; Lin, Weiqin; Chan, Koo Hui; Seow, Swee-Chong

    2016-01-01

    Spontaneous coronary artery dissection is an uncommon cause of acute coronary syndrome. Diagnosis of coronary artery dissection is made on coronary angiogram and prompt revascularisation is the key in management. We present a case of coronary artery dissection with an atypical presentation of cardiac arrhythmia mimicking benign fascicular ventricular tachycardia. A high index of suspicion and early coronary angiogram allowed us to diagnose and treat this potentially life-threatening disease.

  14. Near-infrared reflectance spectroscopy as a novel method to detect demyelination in rat sciatic nerve in vivo

    NASA Astrophysics Data System (ADS)

    Radhakrishnan, Harsha; Senapati, Arun; Peng, Yuan Bo; Kashyap, Dheerendra; Liu, Hanli

    2005-04-01

    This study was done to use near infrared (NIR) spectroscopy to bring out differences in the anatomical substructures in the rat spinal cord and further to differentiate scattering between demyelinated and normal sciatic nerves in rat models, thereby exploring a new methodology to localize MS (multiple Sclerosis) lesions in vivo for animal studies. The experimental setup consisted of a tungsten light source, CCD array spectrometer, and bifurcated optical fibers for light delivery and detection of back scattered light from tissue. The measurement system was calibrated with reflectance standard. The spinal cord of 14 rats was exposed by laminectomy, and the measurements were taken on 8 points at intervals of 1 mm on the right and left lumbar-sacral regions and the central blood vessel. For measurements on the sciatic nerve, the spinal nerves of 84 rats were ligated according to the Chung Model. Measurements were taken on five points on both the ligated and the control nerve side after 1, 4, 7 and 14 days. The reduced scattering coefficient, μs', was found to be higher in the lumbar-sacral regions (34.17 +/- 2.05 cm-1) than that near the central blood vessel (19.9 +/- 3.8 cm-1). Statistically, there was significant difference in scattering between the control side and the ligated side on postoperative days 4, 7, and 14. This study shows a promising diagnostic value in the future for monitoring of demyelinated CNS (central nervous system) diseases, like Multiple Sclerosis.

  15. Severity of Demyelinating and Axonal Neuropathy Mouse Models Is Modified by Genes Affecting Structure and Function of Peripheral Nodes.

    PubMed

    Morelli, Kathryn H; Seburn, Kevin L; Schroeder, David G; Spaulding, Emily L; Dionne, Loiuse A; Cox, Gregory A; Burgess, Robert W

    2017-03-28

    Charcot-Marie-Tooth (CMT) disease is a clinically and genetically heterogeneous group of inherited polyneuropathies. Mutations in 80 genetic loci can cause forms of CMT, resulting in demyelination and axonal dysfunction. The clinical presentation, including sensory deficits, distal muscle weakness, and atrophy, can vary greatly in severity and progression. Here, we used mouse models of CMT to demonstrate genetic interactions that result in a more severe neuropathy phenotype. The cell adhesion molecule Nrcam and the Na(+) channel Scn8a (NaV1.6) are important components of nodes. Homozygous Nrcam and heterozygous Scn8a mutations synergized with both an Sh3tc2 mutation, modeling recessive demyelinating Charcot-Marie-Tooth type 4C, and mutations in Gars, modeling dominant axonal Charcot-Marie-Tooth type 2D. We conclude that genetic variants perturbing the structure and function of nodes interact with mutations affecting the cable properties of axons by thinning myelin or reducing axon diameter. Therefore, genes integral to peripheral nodes are candidate modifiers of peripheral neuropathy.

  16. A review of MRI evaluation of demyelination in cuprizone murine model

    SciTech Connect

    Krutenkova, E. Pan, E.; Khodanovich, M.

    2015-11-17

    The cuprizone mouse model of non-autoimmune demyelination reproduces some phenomena of multiple sclerosis and is appropriate for validation and specification of a new method of non-invasive diagnostics. In the review new data which are collected using the new MRI method are compared with one or more conventional MRI tools. Also the paper reviewed the validation of MRI approaches using histological or immunohistochemical methods. Luxol fast blue histological staining and myelin basic protein immunostaining is widespread. To improve the accuracy of non-invasive conventional MRI, multimodal scanning could be applied. The new quantitative MRI method of fast mapping of the macromolecular proton fraction is a reliable biomarker of myelin in the brain and can be used for research of demyelination in animals. To date, a validation of MPF method on the CPZ mouse model of demyelination is not performed, although this method is probably the best way to evaluate demyelination using MRI.

  17. A review of MRI evaluation of demyelination in cuprizone murine model

    NASA Astrophysics Data System (ADS)

    Krutenkova, E.; Pan, E.; Khodanovich, M.

    2015-11-01

    The cuprizone mouse model of non-autoimmune demyelination reproduces some phenomena of multiple sclerosis and is appropriate for validation and specification of a new method of non-invasive diagnostics. In the review new data which are collected using the new MRI method are compared with one or more conventional MRI tools. Also the paper reviewed the validation of MRI approaches using histological or immunohistochemical methods. Luxol fast blue histological staining and myelin basic protein immunostaining is widespread. To improve the accuracy of non-invasive conventional MRI, multimodal scanning could be applied. The new quantitative MRI method of fast mapping of the macromolecular proton fraction is a reliable biomarker of myelin in the brain and can be used for research of demyelination in animals. To date, a validation of MPF method on the CPZ mouse model of demyelination is not performed, although this method is probably the best way to evaluate demyelination using MRI.

  18. The connectomics of brain demyelination: Functional and structural patterns in the cuprizone mouse model.

    PubMed

    Hübner, Neele S; Mechling, Anna E; Lee, Hsu-Lei; Reisert, Marco; Bienert, Thomas; Hennig, Jürgen; von Elverfeldt, Dominik; Harsan, Laura-Adela

    2017-02-01

    Connectomics of brain disorders seeks to reveal how altered brain function emerges from the architecture of cerebral networks; however the causal impact of targeted cellular damage on the whole brain functional and structural connectivity remains unknown. In the central nervous system, demyelination is typically the consequence of an insult targeted at the oligodendrocytes, the cells forming and maintaining the myelin. This triggered perturbation generates cascades of pathological events that most likely alter the brain connectome. Here we induced oligodendrocyte death and subsequent demyelinating pathology via cuprizone treatment in mice and combining mouse brain resting state functional Magnetic Resonance Imaging and diffusion tractography we established functional and structural pathology-to-network signatures. We demonstrated that demyelinated brain fundamentally reorganizes its intrinsic functional connectivity paralleled by widespread damage of the structural scaffolding. We evidenced default mode-like network as core target of demyelination-induced connectivity modulations and hippocampus as the area with strongest connectional perturbations.

  19. Fasciculations masquerading as minipolymyoclonus in bulbospinal muscular atrophy

    PubMed Central

    Bhat, Sushanth; Ma, Wei; Kozochonok, Elena; Chokroverty, Sudhansu

    2015-01-01

    Minipolymyoclonus has been described in both anterior horn cell disorders and central nervous system degenerative conditions. While its etiology remains unclear and speculative, a central generator has been previously proposed. We describe a case of bulbospinal muscular atrophy (Kennedy's disease), where minipolymyoclonus-like movements corresponded to fasciculations in neurophysiological studies. Our novel finding suggests that the etiologies of minipolymyoclonus in central and peripheral nervous system disorders are distinct, despite outward clinical similarity. The term “minipolyfasciculations” may be more reflective of the underlying process causing minipolymyoclonus-like movements in lower motor neuron disorders. PMID:26019432

  20. Hepatitis B vaccination and central nervous system demyelination: an immunological approach.

    PubMed

    Piaggio, E; Ben Younes, A; Desbois, S; Gout, O; Tourbah, A; Lyon-Caen, O; Liblau, R S

    2005-02-01

    Demyelination events or multiple sclerosis following hepatitis B virus (HBV) vaccination have been reported. We therefore compared the T-cell response to HBsAg in patients with CNS demyelination following HBV vaccination and in HBV-vaccinated healthy individuals. Our data showed no differences in terms of T-cell proliferation or cytokine production between these groups and may help to allay concerns that HBV vaccination might trigger a deleterious immune response.

  1. Endogenous Nkx2.2+/Olig2+ oligodendrocyte precursor cells fail to remyelinate the demyelinated adult rat spinal cord in the absence of astrocytes

    PubMed Central

    Talbott, Jason F.; Loy, David N.; Liu, Ying; Qiu, Mengsheng S.; Bunge, Mary Bartlett; Rao, Mahendra S.; Whittemore, Scott R.

    2010-01-01

    Chronic demyelination is a pathophysiologic component of compressive spinal cord injury (SCI) and a characteristic finding in demyelinating diseases including multiple sclerosis (MS). A better characterization of endogenous cells responsible for successful remyelination is essential for designing therapeutic strategies aimed at restoring functional myelin. The present study examined the spatiotemporal response of endogenous oligodendrocyte precursor cells (OPCs) following ethidium bromide (EB)-induced demyelination of the adult rat spinal cord. Beginning at 2 days post-EB injection (dpi), a robust mobilization of highly proliferative NG2+ cells within the lesion was observed, none of which expressed the oligodendrocyte lineage-associated transcription factor Nkx2.2. At 7 dpi, a significant up-regulation of Nkx2.2 by OPCs within the lesion was observed, 90% of which coexpressed NG2 and virtually all of which coexpressed the bHLH transcription factor Olig2. Despite successful recruitment of Nkx2.2+/Olig2+ OPCs within the lesion, demyelinated axons were not remyelinated by these OPCs in regions lacking astrocytes. Rather, Schwann cell remyelination predominated throughout the central core of the lesion, particularly around blood vessels. Oligodendrocyte remyelination was observed in the astrogliotic perimeter, suggesting a necessary role for astrocytes in oligodendrocyte maturation. In addition, reexpression of the radial glial antigen, RC-1, by reactive astrocytes and ependymal cells was observed following injury. However, these cells did not express the neural stem cell (NSC)-associated transcription factors Sox1 or Sox2, suggesting that the endogenous response is primarily mediated by glial progenitors. In vivo electrophysiology demonstrated a limited and unsustained functional recovery concurrent with endogenous remyelination following EB-induced lesions. PMID:15698615

  2. Antibody responses to peptides of peripheral nerve myelin proteins P0 and P2 in patients with inflammatory demyelinating neuropathy

    PubMed Central

    Inglis, H R; Csurhes, P A; McCombe, P A

    2007-01-01

    Background Antibodies with reactivity to peripheral nerve myelin have previously been found in the serum, and bound to peripheral nerves of patients with Guillain–Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Aim To investigate the presence of antibodies reactive to specific peptide sequences within the myelin proteins P0 and P2 in patients with GBS, in patients with CIDP, in healthy controls and in patients with other neuropathies (ON). Methods Blood was obtained from 48 patients with GBS, 36 with CIDP, 48 with ON and 38 controls. ELISA was used to detect antibody responses to peptides of the human peripheral myelin proteins P0 and P2. Blood samples were collected from patients with GBS in early, peak and recovery stages of GBS to analyse antibody levels throughout the course of the disease. Results Significantly increased total IgG levels were found in patients with GBS compared with other groups. A higher percentage of patients with GBS at the peak of disease had antibody reactivity to P214–25 compared with patients with CIDP and control groups. In patients with GBS and CIDP, the percentages of patients with antibody reactivity to P261–70, and peptides derived from P0, were comparable to the control groups. Although some individual patients with GBS had high titres of reactivity to the peptide antigens tested, most patients with GBS and CIDP had levels of antibody similar to controls. Conclusion Our data suggest that increased IgG levels and increased antibody reactivity to P2 14–25 in patients with GBS at the peak of disease may play a contributory role in the disease process in some patients with demyelinating forms of GBS. PMID:17158557

  3. Effects of deep heating provided by therapeutic ultrasound on demyelinating nerves

    PubMed Central

    Aydin, Elif; Tastaban, Engin; Omurlu, Imran Kurt; Turan, Yasemin; Şendur, Ömer Faruk

    2016-01-01

    [Purpose] Physiotherapeutic heating agents are classified into two groups: superficial-heating agents and deep-heating agents. Therapeutic ultrasound is a deep-heating agent used to treat various musculosketal disorders. Numerous studies have attempted to determine the impact of ultrasound on healthy nerve conduction parameters. However, the instantaneous effects of deep heating via ultrasound on demyelinating nerves do not appear to have been described previously. The present study aimed to assess and compare the impact of ultrasound on demyelinating nerve and healthy nerve conduction parameters. [Subjects and Methods] Carpal tunnel syndrome was used as a focal demyelination model. Thirty-two hands of 25 participants with carpal tunnel syndrome were enrolled in the study. Ultrasound parameters were 3.3 MHz, 1.0 W/cm2, 8 minutes, and continuous wave. Electrodiagnostic studies were performed initially, at the midpoint (4th min), and immediately after (8th min) ultrasound application. [Results] Reduced motor conduction velocity was found in demyelinating nerves at the 4th and 8th minutes. Ulnar nerve onset latency was significantly prolonged in the 8th minute recording, compared to the initial value. There were no significant differences in relative velocity and latency changes between demyelinating and normal nerves. [Conclusion] Deep heating via ultrasound may inversely affect conduction velocity in demyelinating nerves. PMID:27190467

  4. Experimental immunological demyelination enhances regeneration in autograft-repaired long peripheral nerve gaps

    PubMed Central

    Ge, Jun; Zhu, Shu; Yang, Yafeng; Liu, Zhongyang; Hu, Xueyu; Huang, Liangliang; Quan, Xin; Wang, Meng; Huang, Jinghui; Li, Yunqing; Luo, Zhuojing

    2016-01-01

    Peripheral nerve long gap defects are a clinical challenge in the regeneration field. Despite the wide variety of surgical techniques and therapies, autografting is the “gold standard” for peripheral nerve gap reconstruction. The pathological process of Wallerian degeneration from the time of acute injury to efficient regeneration requires several weeks. Regeneration time is critical for nerve reconstruction. Immunological demyelination induced by anti-galactocerebroside antibodies plus guinea pig complement was used to shorten the treatment time. Based on an antigen-antibody complex reaction, the demyelinating agent induced an acute and severe demyelination, leading to the pathological process of Wallerian degeneration during the demyelinating period. This method was used to treat a 12 mm-long sciatic nerve defect in rats. The control groups were injected with one of the demyelinating agent components. The results indicated that anti-galactocerebroside antibodies plus guinea pig complement can significantly shorten treatment time and promote nerve regeneration and functional recovery. In addition, the demyelinating agent can increase the mRNA levels of nerve growth factors and can regulate inflammation. In conclusion, treatment with anti-galactocerebroside antibodies plus guinea pig complement can promote axonal regeneration. This therapy provides a novel method to improve functional recovery in the treatment of long nerve defects. PMID:28008990

  5. Leprosy with Atypical Skin Lesions Masquerading as Relapsing Polychondritis

    PubMed Central

    Munganda, Hariharan; Bangia, Amit; Rani, Uma; Budhiraja, Rajesh; Brajpuriya, Swapnil

    2016-01-01

    Leprosy can present with a variety of clinical manifestations depending on the immune status of the individual. After dermatological and neurological involvement, rheumatic features specially various forms of arthritis are the third most common manifestation of the disease. We describe a unique case of a 22-year-old patient presenting with external ear involvement mimicking relapsing polychondritis along with inflammatory joint symptoms and skin lesions. Ear involvement in relapsing polychondritis characteristically is painful and spares the noncartilaginous ear lobules, in contrast to painless ear involvement in leprosy affecting the lobules as well. Histopathology confirmed the diagnosis, although the ear and skin lesions were not classical of leprosy. Such a presentation of leprosy closely mimicking relapsing polychondritis has not been described previously. Tissue diagnosis should always be attempted whenever possible in patients presenting with autoimmune features, so that inappropriate therapy with immunosuppressants is avoided. PMID:28116186

  6. Mucopolysaccharidosis type IIIB (MPS IIIB) masquerading as a behavioural disorder.

    PubMed

    Brady, Jacqueline; Trehan, Aditi; Landis, Dennis; Toro, Camilo

    2013-05-08

    Inborn errors of metabolism (IEMs) that manifest primarily as psychiatric and behavioural symptoms in childhood are often mistaken for idiopathic primary psychiatric disorders. The pathophysiological basis of these symptoms may be overlooked until later in the disease course when neurological deficits become dominant; this results in a significant delay in establishing a proper diagnosis. To illustrate this, we describe two siblings who presented with behavioural issues and mild learning disabilities in childhood, and were consequently given multiple psychiatric diagnoses. In early adulthood, however, they manifested a rapid cognitive decline. Subsequent cranial MRI imaging revealed progressive brain iron accumulation in deep brain nuclei. Whole exome sequencing and biochemical investigation confirmed the diagnosis of mucopolysaccharidosis type IIIB. Their long diagnostic odyssey illustrates the importance of considering IEMs when assessing individuals with behavioural abnormalities and cognitive impairment.

  7. Anal Neuroendocrine Tumor Masquerading as External Hemorrhoids: A Case Report

    PubMed Central

    Khan, Muhammad; Dirweesh, Ahmed; Alvarez, Chikezie; Conaway, Herbert; Moser, Robert

    2017-01-01

    Neuroendocrine tumors in gastrointestinal (GI) tract are a rare source of GI malignancy with an estimated incidence of 2.5 - 5 per 100,000 people per year and the prevalence of 35 per 100,000. In the GI tract, they are located in decreasing order of frequency in appendix, ileum, rectum, stomach, and colon. Those found in the anal region represent just 1% of all malignancies of the anal canal. Their clinical presentation can be widely varying, sometimes being found incidentally with metastatic disease and an unknown primary source. We report a case of a 60-year-old male who presented with a 2-week history of intermittent bright red blood per rectum and anal pain. He was found to have a lesion in the perianal area which was subsequently diagnosed has a poorly differentiated large cell type neuroendocrine carcinoma (NEC) with hepatic metastasis. PMID:28270879

  8. An additional monogenic disorder that masquerades as multiple sclerosis

    SciTech Connect

    Vahedi, K.; Tournier-Lasserve, E.; Vahedi, K.

    1996-11-11

    In their comprehensive differential diagnosis of monogenic diseases that can mimic multiple sclerosis, Natowicz and Bejjani did not include a newly recognized monogenic disorder known under the acronym of CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy); this disorder can mimic MS clinically and radiologically to a remarkable extent. The underlying histopathological lesion of CADASIL is a non-atherosclerotic, non-amyloid arteriopathy affecting mainly the penetrating medullary arteries to the subcortical white matter and basal ganglia. Electron microscopy shows an abnormal deposit of granular osmiophilic material in the arterial wall. These arterial changes are observed in various tissues even though clinical manifestations seem to be restricted to the central nervous system. The CADASIL gene was mapped recently to chromosome 19 and gene identification is ongoing. 6 refs., 1 fig.

  9. Stiff Person Syndrome Masquerading as Acute Coronary Syndrome.

    PubMed

    Sharma, Ashish; Soe, Myat Han; Singh, Jagdeep; Newsome, Scott D

    2016-01-01

    Stiff person syndrome (SPS) is a rare neuroimmunological disorder characterized by severe progressive muscle stiffness in axial and lower extremity musculature with superimposed painful muscle spasms. Although chest pain is a common reason for SPS patients presenting to the emergency room, this disorder is overlooked and not part of the differential diagnosis of chest pain. Herein, we report on a middle age male presenting with classic symptoms of SPS; however, due to the rarity of this disease, he was initially thought to have acute coronary syndrome. Clinicians should consider the diagnosis of SPS in patients with fluctuating muscle spasms in the torso and/or extremities in the setting of repeated hospitalizations without subsequent symptom relief.

  10. Pmp22 mutant allele-specific siRNA alleviates demyelinating neuropathic phenotype in vivo.

    PubMed

    Lee, Ji-Su; Chang, Eun Hyuk; Koo, Ok Jae; Jwa, Dong Hwan; Mo, Won Min; Kwak, Geon; Moon, Hyo Won; Park, Hwan Tae; Hong, Young Bin; Choi, Byung-Ok

    2017-04-01

    Charcot-Marie-Tooth disease (CMT) is a genetic disorder that can be caused by aberrations in >80 genes. CMT has heterogeneous modes of inheritance, including autosomal dominant, autosomal recessive, X-linked dominant, and X-linked recessive. Over 95% of cases are dominantly inherited. In this study, we investigated whether regulation of a mutant allele by an allele-specific small interfering RNA (siRNA) can alleviate the demyelinating neuropathic phenotype of CMT. We designed 19 different allele-specific siRNAs for Trembler J (Tr-J) mice harboring a naturally occurring mutation (Leu16Pro) in Pmp22. Using a luciferase assay, we identified an siRNA that specifically and selectively reduced the expression level of the mutant allele and reversed the low viability of Schwann cells caused by mutant Pmp22 over-expression in vitro. The in vivo efficacy of the allele-specific siRNA was assessed by its intraperitoneal injection to postnatal day 6 of Tr-J mice. Administration of the allele-specific siRNA to Tr-J mice significantly enhanced motor function and muscle volume, as assessed by the rotarod test and magnetic resonance imaging analysis, respectively. Increases in motor nerve conduction velocity and compound muscle action potentials were also observed in the treated mice. In addition, myelination, as evidenced by toluidine blue staining and electron microscopy, was augmented in the sciatic nerves of the mice after allele-specific siRNA treatment. After validating suppression of the Pmp22 mutant allele at the mRNA level in the Schwann cells of Tr-J mice, we observed increased expression levels of myelinating proteins such as myelin basic protein and myelin protein zero. These data indicate that selective suppression of the Pmp22 mutant allele by non-viral delivery of siRNA alleviates the demyelinating neuropathic phenotypes of CMT in vivo, implicating allele-specific siRNA treatment as a potent therapeutic strategy for dominantly inherited peripheral neuropathies.

  11. The Mitochondrial m-AAA Protease Prevents Demyelination and Hair Greying

    PubMed Central

    Jacquemyn, Julie; Barth, Esther; Langer, Thomas; Niessen, Carien M.; Rugarli, Elena I.

    2016-01-01

    The m-AAA protease preserves proteostasis of the inner mitochondrial membrane. It ensures a functional respiratory chain, by controlling the turnover of respiratory complex subunits and allowing mitochondrial translation, but other functions in mitochondria are conceivable. Mutations in genes encoding subunits of the m-AAA protease have been linked to various neurodegenerative diseases in humans, such as hereditary spastic paraplegia and spinocerebellar ataxia. While essential functions of the m-AAA protease for neuronal survival have been established, its role in adult glial cells remains enigmatic. Here, we show that deletion of the highly expressed subunit AFG3L2 in mature mouse oligodendrocytes provokes early-on mitochondrial fragmentation and swelling, as previously shown in neurons, but causes only late-onset motor defects and myelin abnormalities. In contrast, total ablation of the m-AAA protease, by deleting both Afg3l2 and its paralogue Afg3l1, triggers progressive motor dysfunction and demyelination, owing to rapid oligodendrocyte cell death. Surprisingly, the mice showed premature hair greying, caused by progressive loss of melanoblasts that share a common developmental origin with Schwann cells and are targeted in our experiments. Thus, while both neurons and glial cells are dependant on the m-AAA protease for survival in vivo, complete ablation of the complex is necessary to trigger death of oligodendrocytes, hinting to cell-autonomous thresholds of vulnerability to m-AAA protease deficiency. PMID:27911893

  12. Determining Immune System Suppression versus CNS Protection for Pharmacological Interventions in Autoimmune Demyelination.

    PubMed

    Evonuk, Kirsten S; Moseley, Carson E; Doyle, Ryan E; Weaver, Casey T; DeSilva, Tara M

    2016-09-12

    A major hallmark of the autoimmune demyelinating disease multiple sclerosis (MS) is immune cell infiltration into the brain and spinal cord resulting in myelin destruction, which not only slows conduction of nerve impulses, but causes axonal injury resulting in motor and cognitive decline. Current treatments for MS focus on attenuating immune cell infiltration into the central nervous system (CNS). These treatments decrease the number of relapses, improving quality of life, but do not completely eliminate relapses so long-term disability is not improved. Therefore, therapeutic agents that protect the CNS are warranted. In both animal models as well as human patients with MS, T cell entry into the CNS is generally considered the initiating inflammatory event. In order to assess if a drug protects the CNS, any potential effects on immune cell infiltration or proliferation in the periphery must be ruled out. This protocol describes how to determine whether CNS protection observed after drug intervention is a consequence of attenuating CNS-infiltrating immune cells or blocking death of CNS cells during inflammatory insults. The ability to examine MS treatments that are protective to the CNS during inflammatory insults is highly critical for the advancement of therapeutic strategies since current treatments reduce, but do not completely eliminate, relapses (i.e., immune cell infiltration), leaving the CNS vulnerable to degeneration.

  13. Determining Immune System Suppression versus CNS Protection for Pharmacological Interventions in Autoimmune Demyelination

    PubMed Central

    Doyle, Ryan E.; Weaver, Casey T.; DeSilva, Tara M.

    2016-01-01

    A major hallmark of the autoimmune demyelinating disease multiple sclerosis (MS) is immune cell infiltration into the brain and spinal cord resulting in myelin destruction, which not only slows conduction of nerve impulses, but causes axonal injury resulting in motor and cognitive decline. Current treatments for MS focus on attenuating immune cell infiltration into the central nervous system (CNS). These treatments decrease the number of relapses, improving quality of life, but do not completely eliminate relapses so long-term disability is not improved. Therefore, therapeutic agents that protect the CNS are warranted. In both animal models as well as human patients with MS, T cell entry into the CNS is generally considered the initiating inflammatory event. In order to assess if a drug protects the CNS, any potential effects on immune cell infiltration or proliferation in the periphery must be ruled out. This protocol describes how to determine whether CNS protection observed after drug intervention is a consequence of attenuating CNS-infiltrating immune cells or blocking death of CNS cells during inflammatory insults. The ability to examine MS treatments that are protective to the CNS during inflammatory insults is highly critical for the advancement of therapeutic strategies since current treatments reduce, but do not completely eliminate, relapses (i.e., immune cell infiltration), leaving the CNS vulnerable to degeneration. PMID:27685467

  14. Nigella sativa amliorates inflammation and demyelination in the experimental autoimmune encephalomyelitis-induced Wistar rats.

    PubMed

    Noor, Neveen A; Fahmy, Heba M; Mohammed, Faten F; Elsayed, Anwar A; Radwan, Nasr M

    2015-01-01

    Multiple sclerosis (MS) is the major, immune-mediated, demyelinating neurodegenerative disease of the central nervous system (CNS). Experimental autoimmune encephalomyelitis (EAE) is a well-established animal model of MS. The aim of the present study was to investigate the protective and ameliorative effects of N. sativa seeds (2.8 g/kg body weight) in EAE-induced Wistar rats. EAE-induced rats were divided into: 1- EAE-induced rats ("EAE" group). 2- "N. sativa + EAE" group received daily oral administration of N. sativa 2 weeks prior EAE induction until the end of the experiment. 3- "EAE + N. sativa" group received daily oral administration of N. sativa after the appearance of first clinical signs until the end of the experiment. All animals were decapitated at the 28th day post EAE-induction. EAE was investigated using histopathological, immunohistochemical and ultrastructural examinations in addition to determination of some oxidative stress parameters in the cerebellum and medulla. N. sativa suppressed inflammation observed in EAE-induced rats. In addition, N. sativa enhanced remyelination in the cerebellum. Moreover, N. sativa reduced the expression of transforming growth factor beta 1 (TGF β1). N. sativa seeds could provide a promising agent effective in both the protection and treatment of EAE.

  15. Occupational exposure and risk of central nervous system demyelination.

    PubMed

    Valery, P C; Lucas, R M; Williams, D B; Pender, M P; Chapman, C; Coulthard, A; Dear, K; Dwyer, T; Kilpatrick, T J; McMichael, A J; van der Mei, I; Taylor, B V; Ponsonby, A-L

    2013-05-01

    Inconsistent evidence exists regarding the association between work-related factors and risk of multiple sclerosis (MS). We examined the association between occupational exposures and risk of a first clinical diagnosis of central nervous system demyelination (FCD), which is strongly associated with progression to MS, in a matched case-control study of 276 FCD cases and 538 controls conducted in Australia (2003-2006). Using a personal residence and work calendar, information on occupational history and exposure to chemicals and animals was collected through face-to-face interviews. Few case-control differences were noted. Fewer cases had worked as professionals (≥6 years) than controls (adjusted odds ratio (AOR) = 0.60, 95% confidence interval (CI): 0.37, 0.96). After further adjustment for number of children, cases were more likely to have ever been exposed to livestock than controls (AOR = 1.54, 95% CI: 1.03, 2.29). Among women, there was an increase in FCD risk associated with 10 or more years of exposure to livestock (AOR = 2.78, 95% CI: 1.22, 6.33) or 6 or more years of farming (AOR = 2.00, 95% CI: 1.23, 3.25; also adjusted for number of children). Similar findings were not evident among men. Thus, farming and exposure to livestock may be important factors in the development of FCD among women, with this finding further revealed after the confounding effect of parity or number of children is considered.

  16. Electrophysiological features of POEMS syndrome and chronic inflammatory demyelinating polyneuropathy.

    PubMed

    Guo, Xiuming; Qin, Xinyue; Zhang, Yuping; Huang, Cheng; Yu, Gang

    2014-04-01

    Polyneuropathy is often an initial manifestation of polyneuropathy, organomegaly, endocrinopathy, M protein and skin changes (POEMS) syndrome and therefore this disorder is frequently misdiagnosed as chronic inflammatory demyelinating polyneuropathy (CIDP). We reviewed electrophysiological data in 20 patients with POEMS syndrome and 36 matched patients with CIDP to compare the electrophysiological features of POEMS syndrome and CIDP. Compared with CIDP controls, POEMS patients demonstrated (1) less prolonged distal motor latency and less reduced motor nerve and sensory nerve conduction velocities, (2) greater reduction of amplitudes of compound motor action potentials (CMAP) in distal stimulation, and similar reduction of amplitudes of CMAP in proximal stimulation, (3) similar reduction of amplitudes of sensory nerve action potentials (SNAP) in median and ulnar nerves, and a greater reduction of amplitudes of SNAP in tibial and peroneal nerves, (4) less temporal dispersion, (5) less frequent conduction block, (6) more frequent neurogenic injury in the muscles of the upper and lower limbs, and more frequent neurogenic injury in the muscles of the lower than upper limbs, (7) similar F wave and H reflex abnormalities, and (8) less frequent skin sympathetic response abnormalities. We concluded that before development of typical clinical manifestations, POEMS neuropathy can be distinguished from CIDP by neural electrophysiological examination. These electrophysiological features can be used for early diagnosis and initiating correct treatment of POEMS syndrome.

  17. A nationwide survey of pediatric acquired demyelinating syndromes in Japan

    PubMed Central

    Yamaguchi, Y.; Kira, R.; Ishizaki, Y.; Sakai, Y.; Sanefuji, M.; Ichiyama, T.; Oka, A.; Kishi, T.; Kimura, S.; Kubota, M.; Takanashi, J.; Takahashi, Y.; Tamai, H.; Natsume, J.; Hamano, S.; Hirabayashi, S.; Maegaki, Y.; Mizuguchi, M.; Minagawa, K.; Yoshikawa, H.; Kira, J.; Kusunoki, S.; Hara, T.

    2016-01-01

    Objective: To investigate the clinical and epidemiologic features of pediatric acquired demyelinating syndromes (ADS) of the CNS in Japan. Methods: We conducted a nationwide survey and collected clinical data on children with ADS aged 15 years or younger, who visited hospitals between 2005 and 2007. Results: Among 977 hospitals enrolled, 723 (74.0%) responded to our inquiries and reported a total of 439 patients as follows: 244 with acute disseminated encephalomyelitis (ADEM), 117 with multiple sclerosis (MS), 14 with neuromyelitis optica (NMO), and 64 with other ADS. We collected and analyzed detailed data from 204 cases, including those with ADEM (66), MS (58), and NMO (10). We observed the following: (1) the estimated annual incidence rate of pediatric ADEM in Japan was 0.40 per 100,000 children (95% confidence interval [CI], 0.34–0.46), with the lowest prevalence in the north; (2) the estimated prevalence rate of MS was 0.69 per 100,000 children (95% CI, 0.58–0.80), with the lowest prevalence in the south; (3) NMO in Japan was rare, with an estimated prevalence of 0.06 per 100,000 children (95% CI, 0.04–0.08); and (4) the sex ratio and mean age at onset varied by ADS type, and (5) male/female ratios correlated with ages at onset in each ADS group. Conclusions: Our results clarify the characteristic clinical features of pediatric ADS in the Japanese population. PMID:27742816

  18. Stance Postural Strategies in Patients with Chronic Inflammatory Demyelinating Polyradiculoneuropathy

    PubMed Central

    Missori, Paolo; Trompetto, Carlo; Fattapposta, Francesco

    2016-01-01

    Introduction Polyneuropathy leads to postural instability and an increased risk of falling. We investigated how impaired motor impairment and proprioceptive input due to neuropathy influences postural strategies. Methods Platformless bisegmental posturography data were recorded in healthy subjects and patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Each subject stood on the floor, wore a head and a hip electromagnetic tracker. Sway amplitude and velocity were recorded and the mean direction difference (MDD) in the velocity vector between trackers was calculated as a flexibility index. Results Head and hip postural sway increased more in patients with CIDP than in healthy controls. MDD values reflecting hip strategies also increased more in patients than in controls. In the eyes closed condition MDD values in healthy subjects decreased but in patients remained unchanged. Discussion Sensori-motor impairment changes the balance between postural strategies that patients adopt to maintain upright quiet stance. Motor impairment leads to hip postural strategy overweight (eyes open), and prevents strategy re-balancing when the sensory context predominantly relies on proprioceptive input (eyes closed). PMID:26977594

  19. Inflammatory responses in aggregating rat brain cell cultures subjected to different demyelinating conditions.

    PubMed

    Defaux, Antoinette; Zurich, Marie-Gabrielle; Honegger, Paul; Monnet-Tschudi, Florianne

    2010-09-24

    To study inflammatory reactions occurring in relation to demyelination, aggregating rat brain cell cultures were subjected to three different demyelinating insults, i.e., (i) lysophosphatidylcholine (LPC), (ii) interferon-gamma combined with lipopolysaccharide (IFN-gamma+LPS), and (iii) anti-MOG antibodies plus complement (alpha-MOG+C). Demyelination was assessed by measuring the expression of myelin basic protein (MBP) and myelin oligodendrocyte glycoprotein (MOG), and the activity of 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP). The accompanying inflammatory reactions were examined by the quantification of microglia-specific staining, by immunostaining for glial fibrillary acidic protein (GFAP), and by measuring the mRNA expression of a panel of inflammation-related genes. It was found that all three demyelinating insults decreased the expression of MBP and MOG, and induced microglial reactivity. LPC and alpha-MOG+C, but not IFN-gamma+LPS, decreased CNP activity; they also caused the appearance of macrophagic microglia, and increased GFAP staining indicating astrogliosis. LPC affected also the integrity of neurons and astrocytes. LPC and IFN-gamma+LPS upregulated the expression of the inflammation-related genes IL-6, TNF-alpha, Ccl5, Cxcl1, and iNOS, although to different degrees. Other inflammatory markers were upregulated by only one of the three insults, e.g., Cxcl2 by LPC; IL-1beta and IL-15 by IFN-gamma+LPS; and IFN-gamma by alpha-MOG+C. These findings indicate that each of the three demyelinating insults caused distinct patterns of demyelination and inflammatory reactivity, and that of the demyelinating agents tested only LPC exhibited general toxicity.

  20. Inflammation and primary demyelination induced by the intraspinal injection of lipopolysaccharide.

    PubMed

    Felts, Paul A; Woolston, Anne-Marie; Fernando, Himali B; Asquith, Stephen; Gregson, Norman A; Mizzi, Oliver J; Smith, Kenneth J

    2005-07-01

    Inflammation is a prominent feature of several disorders characterized by primary demyelination, but it is not clear whether a relationship exists between inflammation and myelin damage. We have found that substantial demyelination results from the focal inflammatory lesion caused by the injection of lipopolysaccharide (LPS; 200 ng) directly into the rat dorsal funiculus. Within 24 h, such injections caused a focal inflammatory response consisting of a substantial number of polymorphonuclear cells and ED1-positive and inducible nitric oxide synthase (iNOS)-positive macrophages/microglia. The number of inflammatory cells was substantially reduced by day 7. OX-52-positive T-cells were less frequently observed but were present in the meninges at 8 h, reached a maximum in the dorsal funiculus at 7 days, and were rare at 14 days. The inflammation was followed by the appearance of a large lesion of primary demyelination that encompassed up to approximately 75% of the cross-sectional area of the dorsal funiculus. Treatment with dexamethasone significantly reduced the number of cells expressing iNOS, but did not prevent the demyelination. By 28 days the lesions were largely remyelinated, usually by Schwann cells. These changes were not observed in control, saline-injected animals. We conclude that the intraspinal injection of LPS results in inflammation and subsequently in prominent demyelination. The mechanisms underlying the demyelination are not clear, but it is notable that it typically begins with disruption of the adaxonal myelin. Indeed, there is an early loss of myelin-associated glycoprotein within the lesion, despite the persistence of proteolipid protein. This combination is a feature of the pattern III lesion recently described in multiple sclerosis (Lucchinetti et al., 2000), and we therefore suggest that LPS-induced demyelination may serve as the first experimental model available for the study of this type of multiple sclerosis lesion.

  1. Multiple sclerosis deep grey matter: the relation between demyelination, neurodegeneration, inflammation and iron.

    PubMed

    Haider, Lukas; Simeonidou, Constantina; Steinberger, Günther; Hametner, Simon; Grigoriadis, Nikolaos; Deretzi, Georgia; Kovacs, Gabor G; Kutzelnigg, Alexandra; Lassmann, Hans; Frischer, Josa M

    2014-12-01

    In multiple sclerosis (MS), diffuse degenerative processes in the deep grey matter have been associated with clinical disabilities. We performed a systematic study in MS deep grey matter with a focus on the incidence and topographical distribution of lesions in relation to white matter and cortex in a total sample of 75 MS autopsy patients and 12 controls. In addition, detailed analyses of inflammation, acute axonal injury, iron deposition and oxidative stress were performed. MS deep grey matter was affected by two different processes: the formation of focal demyelinating lesions and diffuse neurodegeneration. Deep grey matter demyelination was most prominent in the caudate nucleus and hypothalamus and could already be seen in early MS stages. Lesions developed on the background of inflammation. Deep grey matter inflammation was intermediate between low inflammatory cortical lesions and active white matter lesions. Demyelination and neurodegeneration were associated with oxidative injury. Iron was stored primarily within oligodendrocytes and myelin fibres and released upon demyelination. In addition to focal demyelinated plaques, the MS deep grey matter also showed diffuse and global neurodegeneration. This was reflected by a global reduction of neuronal density, the presence of acutely injured axons, and the accumulation of oxidised phospholipids and DNA in neurons, oligodendrocytes and axons. Neurodegeneration was associated with T cell infiltration, expression of inducible nitric oxide synthase in microglia and profound accumulation of iron. Thus, both focal lesions as well as diffuse neurodegeneration in the deep grey matter appeared to contribute to the neurological disabilities of MS patients.

  2. Interleukin‐10 is a critical regulator of white matter lesion containment following viral induced demyelination

    PubMed Central

    Puntambekar, Shweta S.; Hinton, David R.; Yin, Xinghua; Savarin, Carine; Bergmann, Cornelia C.; Trapp, Bruce D.

    2015-01-01

    Neurotropic coronavirus induces an acute encephalomyelitis accompanied by focal areas of demyelination distributed randomly along the spinal column. The initial areas of demyelination increase only slightly after the control of infection. These circumscribed focal lesions are characterized by axonal sparing, myelin ingestion by macrophage/microglia, and glial scars associated with hypertrophic astrocytes, which proliferate at the lesion border. Accelerated virus control in mice lacking the anti‐inflammatory cytokine IL‐10 was associated with limited initial demyelination, but low viral mRNA persistence similar to WT mice and declining antiviral cellular immunity. Nevertheless, lesions exhibited sustained expansion providing a model of dysregulated white matter injury temporally remote from the acute CNS insult. Expanding lesions in the absence of IL‐10 are characterized by sustained microglial activation and partial loss of macrophage/microglia exhibiting an acquired deactivation phenotype. Furthermore, IL‐10 deficiency impaired astrocyte organization into mesh like structures at the lesion borders, but did not prevent astrocyte hypertrophy. The formation of discrete foci of demyelination in IL‐10 sufficient mice correlated with IL‐10 receptor expression exclusively on astrocytes in areas of demyelination suggesting a critical role for IL‐10 signaling to astrocytes in limiting expansion of initial areas of white matter damage. GLIA 2015;63:2106–2120 PMID:26132901

  3. Multiple sclerosis deep grey matter: the relation between demyelination, neurodegeneration, inflammation and iron

    PubMed Central

    Haider, Lukas; Simeonidou, Constantina; Steinberger, Günther; Hametner, Simon; Grigoriadis, Nikolaos; Deretzi, Georgia; Kovacs, Gabor G; Kutzelnigg, Alexandra; Lassmann, Hans; Frischer, Josa M

    2014-01-01

    In multiple sclerosis (MS), diffuse degenerative processes in the deep grey matter have been associated with clinical disabilities. We performed a systematic study in MS deep grey matter with a focus on the incidence and topographical distribution of lesions in relation to white matter and cortex in a total sample of 75 MS autopsy patients and 12 controls. In addition, detailed analyses of inflammation, acute axonal injury, iron deposition and oxidative stress were performed. MS deep grey matter was affected by two different processes: the formation of focal demyelinating lesions and diffuse neurodegeneration. Deep grey matter demyelination was most prominent in the caudate nucleus and hypothalamus and could already be seen in early MS stages. Lesions developed on the background of inflammation. Deep grey matter inflammation was intermediate between low inflammatory cortical lesions and active white matter lesions. Demyelination and neurodegeneration were associated with oxidative injury. Iron was stored primarily within oligodendrocytes and myelin fibres and released upon demyelination. In addition to focal demyelinated plaques, the MS deep grey matter also showed diffuse and global neurodegeneration. This was reflected by a global reduction of neuronal density, the presence of acutely injured axons, and the accumulation of oxidised phospholipids and DNA in neurons, oligodendrocytes and axons. Neurodegeneration was associated with T cell infiltration, expression of inducible nitric oxide synthase in microglia and profound accumulation of iron. Thus, both focal lesions as well as diffuse neurodegeneration in the deep grey matter appeared to contribute to the neurological disabilities of MS patients. PMID:24899728

  4. Deterioration after corticosteroids in CIDP may be associated with pure focal demyelination pattern

    PubMed Central

    2014-01-01

    Background In the PREDICT study, a randomised controlled trial comparing dexamethasone with prednisolone in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), almost a quarter of patients deteriorated soon after starting treatment. The primary objective of this post-hoc analysis was to test the hypothesis that a focal demyelination pattern is associated with early deterioration after corticosteroid treatment and to explore whether various clinical characteristics are associated with deterioration after corticosteroid treatment. Methods Clinical outcome was categorised into early deterioration and non-early deterioration. A neurophysiologist blinded for treatment outcome scored electrophysiological data into following categories: pure focal versus non-focal distribution of demyelination and no/minor versus moderate/severe sensory involvement. Additionally, we compared electrophysiological and clinical baseline parameters, with emphasis on previously reported possible associations. Results Early deterioration was found in 7 out of 33 patients (21%). Ten patients had pure focal distribution of demyelination, of whom 5 had early deterioration; 23 patients had non-focal distribution, of whom 2 had early deterioration (p = 0.02). Higher mean median nerve sensory nerve conduction velocity (SNCV) was found in patients with early deterioration compared to patients with non-early deterioration (52.6 and respectively 40.8 m/s, p = 0.02). Conclusion Pure focal distribution of demyelination and lesser sensory electrophysiological abnormalities may be associated with early deterioration in CIDP patients treated with corticosteroids. PMID:24708554

  5. Subcutaneous Fungal Cyst Masquerading as Benign Lesions – A Series of Eight Cases

    PubMed Central

    Varghese, Renu G’Boy; Phansalkar, Manjiri; Ramdas, Anita; K, Authy; G, Thangiah

    2015-01-01

    Background Subcutaneous fungal infections are caused by penetration of the causative fungi into the subcutaneous layer and are usually localised. We present a series of eight cases with subcutaneous fungal cystic lesions masquerading as benign lesions. Materials and Methods A retrospective study was conducted on subcutaneous fungal infections seen between January 2007 to July 2014 in the Department of Pathology. Eight patients with biopsy proven subcutaneous fungal infection were included. We collected and analysed their demographic, clinical and histopathological details. Results Among eight patients, six were male and two were female. The mean age was 47 years (Range: 21-70). All the eight patients presented with non-tender cystic swelling. The size of the swellings varied from a minimum of 3x3 cm to maximum of 10x4 cm. Out of eight, hand was involved in three, forearm in one, elbow in two, leg in one and foot in one. On H&E staining, all the cases showed fibro collagenous cyst wall, lined by histiocytes, granulomatous reaction, foreign body type of giant cells with acute and chronic inflammatory infiltrate containing fungal elements. Six were identified as hyalohyphomycosis and two were identified as phaeohyphomycotic cysts based on pigmentation of hyphae. Conclusion Fungal infection should be suspected in all subcutaneous cystic lesions. Excised tissue should always be sent for culture and histopathology. PMID:26557537

  6. Scleroderma renal crisis or thrombotic thrombocytopenic purpura: seeing through the masquerade.

    PubMed

    Keeler, Emily; Fioravanti, Gloria; Samuel, Bensson; Longo, Santo

    2015-01-01

    SCLERODERMA: renal crisis (SRC), a somewhat rare but serious complication of systemic scleroderma, is one of only a few known rheumatologic emergencies; it presents in as many as 10% of patients with scleroderma. Before the use of angiotensin converting enzyme (ACE) inhibitors to treat SRC, the mortality rate for SRC was extremely high-as much as 90% after 1 year. However, the mortality rate has significantly improved with the early and aggressive use of ACE inhibitors. SRC typically includes acute renal failure and accelerated hypertension. Patients may report headache, changes in vision, fever, dyspnea, and encephalopathy. Laboratory study results can show elevated creatinine levels, thrombocytopenia, and microangiopathic hemolytic anemia (MAHA) with schistocytes on blood smear. Given this clinical and laboratory presentation, SRC can easily be mistaken for TTP in clinical practice, as we demonstrate in 2 presentations of similar cases of SRC, the first in a 36-year-old Caucasian woman and the second in a 54-year-old Caucasian woman. In both cases, SRC masqueraded as TTP, and both patients were almost mistakenly treated for TTP until the clinical picture changed and certain laboratory test and kidney biopsy results confirmed otherwise.

  7. High-mass twins & resolution of the reconfinement, masquerade and hyperon puzzles of compact star interiors

    SciTech Connect

    Blaschke, David; Alvarez-Castillo, David E.

    2016-01-22

    We aim at contributing to the resolution of three of the fundamental puzzles related to the still unsolved problem of the structure of the dense core of compact stars (CS): (i) the hyperon puzzle: how to reconcile pulsar masses of 2 M{sub ⊙} with the hyperon softening of the equation of state (EoS); (ii) the masquerade problem: modern EoS for cold, high density hadronic and quark matter are almost identical; and (iii) the reconfinement puzzle: what to do when after a deconfinement transition the hadronic EoS becomes favorable again? We show that taking into account the compositeness of baryons (by excluded volume and/or quark Pauli blocking) on the hadronic side and confining and stiffening effects on the quark matter side results in an early phase transition to quark matter with sufficient stiffening at high densities which removes all three present-day puzzles of CS interiors. Moreover, in this new class of EoS for hybrid CS falls the interesting case of a strong first order phase transition which results in the observable high mass twin star phenomenon, an astrophysical observation of a critical endpoint in the QCD phase diagram.

  8. The frequency of 'occult' ventricular fibrillation masquerading as a flat line in prehospital cardiac arrest.

    PubMed

    Cummins, R O; Austin, D

    1988-08-01

    We investigated the frequency with which a "vector of ventricular fibrillation" may exist in persons in prehospital cardiac arrest. Emergency medical technicians trained in defibrillation were directed to record the rhythm in three different monitor leads whenever they noted an initial flat line. Before these lead switches, the technicians performed a flat line protocol that included inspection of the lead connections to the patient and to the defibrillator, and checks of the calibration and battery status of the devices. They performed this flat line protocol for 127 cardiac arrest patients; 118 were in confirmed asystole after technical problems were corrected. Ventricular fibrillation was detected in only three (2.5%) when the monitor lead was switched. Initial technical problems were more frequent and were identified for ten patients (8%). The frequency of occult ventricular fibrillation (three of 118 asystolic patients) yields a 95% confidence that the true frequency is no greater than 8% to 9%. This suggests that ventricular fibrillation masquerading as asystole is rare. These data do not support protocols for empiric countershocks of patients with an initial flat line on the monitor.

  9. A rare case of metastatic germ cell tumor to stomach and duodenum masquerading as signet ring cell adenocarcinoma

    PubMed Central

    Sundaram, Sridhar; Patil, Prachi; Mehta, Shaesta; Ramadwar, Mukta

    2016-01-01

    Adenocarcinomas are the most common cancers affecting stomach. However gastrointestinal stromal tumors (GIST), lymphomas and neuroendocrine tumors (NETs) can also affect the stomach. But stomach is relatively rare site of involvement by metastasis. In this case report a rare metastasis of germ cell tumor (GCT) into stomach is described which clinically and endoscopically masquerade as primary gastric cancers. But detailed clinical examination and vigilant histopathological reporting proves the origin of tumor distant from stomach and thereby change the whole approach of management. PMID:27668229

  10. Serum cytokine and chemokine profiles in patients with chronic inflammatory demyelinating polyneuropathy.

    PubMed

    Beppu, Minako; Sawai, Setsu; Misawa, Sonoko; Sogawa, Kazuyuki; Mori, Masahiro; Ishige, Takayuki; Satoh, Mamoru; Nomura, Fumio; Kuwabara, Satoshi

    2015-02-15

    To identify serum cytokine networks specific to chronic inflammatory demyelinating polyneuropathy (CIDP), serum samples of two subgroups (18 patients with typical CIDP and 12 patients with multifocal acquired demyelinating sensory and motor neuropathy [MADSAM]) were analyzed with multiplex magnetic bead-based cytokine assay. TNF-α, HGF, MIP-1β and IL-1β levels were significantly higher in total CIDP patients than in normal controls. Of these, HGF levels were elevated in typical CIDP patients, but not in MADSAM patients. Patients with high HGF levels showed good responses to steroid treatment. Different cytokine profiles among the CIDP subtypes presumably reflect differences in pathophysiology.

  11. Osmotic demyelination syndrome as a consequence of treating hyperammonemia in a patient with ornithine transcarbamylase deficiency.

    PubMed

    Cardenas, Javier F; Bodensteiner, John B

    2009-07-01

    A 7-year-old female patient with a new diagnosis of ornithine transcarbamylase deficiency was treated for hyperammonemia with a standard protocol. Several days later, she developed ataxia, dysmetria, and dysarthria. Magnetic resonance imaging of the brain demonstrated pontine and extrapontine white matter changes consistent with osmotic demyelination. Classically described as a consequence of hyponatremia treatment, osmotic demyelination syndrome has rarely been associated with other entities. This case suggests a potentially serious complication of the standard therapy for hyperammonemia in patients with ornithine transcarbamylase deficiency.

  12. Liposomal glucocorticosteroids in treatment of chronic autoimmune demyelination: long-term protective effects and enhanced efficacy of methylprednisolone formulations.

    PubMed

    Linker, Ralf A; Weller, Charlotte; Lühder, Fred; Mohr, Alexander; Schmidt, Jens; Knauth, Michael; Metselaar, Josbert M; Gold, Ralf

    2008-06-01

    Liposomal encapsulation leads to enhanced efficacy of glucocorticosteroids (GS) in treatment of autoimmune diseases. Here we compare liposomal prednisolone (PL) to liposomal methylprednisolone (MPL) in chronic-relapsing myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (EAE), a model closely reflecting aspects of multiple sclerosis (MS). At the maximum of the first relapse, a single dose of PL or MPL was applied at 10 mg/kg or at 4 mg/kg and compared to classical methylprednisolone (MP) pulse therapy. PL at 10 mg/kg was superior to free MP with long-term efficacy and a sustained protection even during the second and third relapse. At the same time, in vivo magnetic resonance imaging of rat brains revealed a significant reduction of T2-lesions after PL application. Comparison of PL and MPL at 10 mg/kg disclosed superior effects for MPL with an enhanced reduction of inflammatory infiltration as well as preservation of myelin and axons. Dose titration experiments underscored a dose-dependent efficacy of liposomal GS with a sustained efficacy especially of the higher dosage. In histological analyses, PL10 was superior in reducing macrophage and T cell infiltration as well as demyelination and axonal loss while the lower dosages were still at least as effective as free MP. FACS analyses revealed an effect of liposome formulations on T cell numbers, the CD4/CD8 ratio, frequencies of regulatory T cells and adhesion molecule expression. In summary, liposomal GS and especially methylprednisolone formulations display an enhanced efficacy not only in acute inflammatory, but also in chronic demyelinating models of MS and confer long-term protection from relapses. These findings lay the groundwork for applying liposomal GS in clinical MS trials in the near future.

  13. Demyelinating evidences in CMS rat model of depression: a DTI study at 7 T.

    PubMed

    Hemanth Kumar, B S; Mishra, S K; Trivedi, R; Singh, S; Rana, P; Khushu, S

    2014-09-05

    Depression is among the most debilitating diseases worldwide. Long-term exposure to stressors plays a major role in development of human depression. Chronic mild stress (CMS) seems to be a valid animal model for depression. Diffusion tensor imaging (DTI) is capable of inferring microstructural abnormalities of the white matter and has shown to serve as non-invasive marker of specific pathology. We developed a CMS rat model of depression and validated with behavioral experiments. We measured the diffusion indices (mean diffusivity (MD), fractional anisotropy (FA), axial (λ∥) and radial (λ⊥) diffusivity) to investigate the changes in CMS rat brain during depression onset. Diffusion indices have shown to be useful to discriminate myelin damage from axon loss. DTI was performed in both control and CMS rats (n=10, in each group) and maps of FA, MD, λ∥ and λ⊥ diffusivity values were generated using in-house built software. The diffusion indices were calculated by region of interest (ROI) analysis in different brain regions like the frontal cortex, hippocampus, hypothalamus, cingulum, thalamus, caudate putamen, corpus callosum, cerebral peduncle and sensory motor cortex. The results showed signs of demyelination, reflected by increased MD, decreased FA and increased λ⊥. The results also suggest a possible role of edema or inflammation concerning the brain morphology in CMS rats. The overall finding using DTI suggests there might be a major role of loss of myelin sheath, which leads to disrupted connectivity between the limbic area and the prefrontal cortex during the onset of depression. Our findings indicate that interpretation of these indices may provide crucial information about the type and severity of mood disorders.

  14. Epidemiologic variability of chronic inflammatory demyelinating polyneuropathy with different diagnostic criteria: study of a UK population.

    PubMed

    Rajabally, Yusuf A; Simpson, Benjamin S; Beri, Sushil; Bankart, John; Gosalakkal, Jayaprakash A

    2009-04-01

    Epidemiologic data on chronic inflammatory demyelinating polyneuropathy (CIDP) is limited, and previous studies have shown variable results. The frequencies of CIDP subtypes remain unknown. Variations due to use of different diagnostic criteria have not been studied. We examined the prevalence and incidence of CIDP in Leicestershire and Rutland, UK (population 963,600). Prevalence day was 1 May 2008. The prevalence of CIDP fulfilling the 2006 clinical and electrophysiologic European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) criteria was 4.77 per 100,000 (95% confidence interval [CI] 3.49-6.37). Using the 1991 American Academy of Neurology (AAN) criteria, the prevalence was 1.97 per 100,000 in this population (95% CI 1.19-3.08). Lewis-Sumner syndrome was diagnosed in 15.2% of patients, and 23.9% had pure sensory onset. Over 40% required no immunotherapy, and 84.6% of those treated responded. More than 80% of the AAN criteria-negative but EFNS/PNS criteria-positive patients were responsive to treatment. Both sets of criteria were equally likely to identify patients who required therapy. The mean annual incidence rate over the 3 years preceding the prevalence day was 0.70 per 100,000/year using EFNS/PNS criteria (95% CI 0.43-1.08), and 0.35 per 100,000/year using AAN criteria (95% CI 0.17-0.64). We conclude that the AAN criteria may underestimate prevalence and incidence of the disease. The EFNS/PNS criteria provide higher diagnostic sensitivity and are of greater clinical relevance, and they also offer a useful breakdown of the epidemiologic data for CIDP subtypes.

  15. A rare presentation of Legionnaires' disease.

    PubMed

    Delicata, Mark; Banerjee, Amit

    2015-07-01

    We present an interesting case of Legionnaires' disease masquerading as acute pyelonephritis, with complete absence of respiratory symptoms on admission. A 45-year-old man was diagnosed with Legionnaires' disease 2 days after presenting to hospital with dysuria and right loin pain. He became critically unwell during the hospital admission, with headache, uncontrolled fever, breathlessness, decreasing oxygen saturations and increasing oxygen requirements. A CT pulmonary angiography demonstrated right upper lobar consolidation and Legionella urinary antigen was positive. He was treated with ciprofloxacin and rifampicin and made a full recovery.

  16. The Anti-Aging Protein Klotho Enhances Remyelination Following Cuprizone-Induced Demyelination.

    PubMed

    Zeldich, Ella; Chen, Ci-Di; Avila, Robin; Medicetty, Satish; Abraham, Carmela R

    2015-10-01

    The current study examined whether overexpression of Klotho (KL) in transgenic mice can enhance remyelination following cuprizone-induced demyelination and improves the clinical outcome in experimental autoimmune encephalomyelitis (EAE). Demyelination was achieved by feeding transgenic mice overexpressing the transmembrane form of Klotho (KL-OE) and wild-type (WT) littermates cuprizone-containing chow for 6 weeks. The animals were then allowed to remyelinate for 3 weeks. Paraphenylenediamine staining and platelets-derived growth factor receptor α (PDGFRα) and glutathione S-transferase pi (GSTpi) immunohistochemistry were performed on corpus callosum (CC) sections for quantification of myelin and progenitor and mature oligodendrocytes, respectively. The EAE model was induced with the MOG35-55 peptide. The animals were scored daily for clinical symptoms for 30 days. Following 6 weeks of demyelination, both KL-OE mice and WT littermates demonstrated almost complete and comparable demyelination of the CC. However, the level of spontaneous remyelination was increased approximately two-fold in KL-OE mice, although no significant differences in the numbers of PDGFRα and GSTpi-positive cells were observed. Following EAE induction, Klotho overexpression did not affect the clinical scores, likely due to the different roles Klotho plays in the brain and spinal cord. Thus, increasing Klotho expression should be considered as a therapy for enhancing remyelination in the brains of individuals with multiple sclerosis.

  17. Adult onset leukodystrophy with neuroaxonal spheroids and demyelinating plaque-like lesions.

    PubMed

    Martinez-Saez, Elena; Shah, Sachit; Costa, Carme; Fleminger, Simon; Connor, Stephen; Bodi, Istvan

    2012-06-01

    Adult onset leukodystrophy with neuroaxonal spheroids is an uncommon cause of dementia. Both hereditary (autosomal dominant) and sporadic cases have been described. A 41-year-old African woman presented with inappropriate behavior and personality change consistent with frontal lobe dysfunction. MRI demonstrated diffuse frontoparietal white matter signal abnormality and volume loss, as well as focal enhancing white matter lesions, while CT scan showed white matter calcifications. She had been gradually deteriorating over the last 5 years, diagnosed as having progressive demyelinating illness. She died of recurrent chest infections. There was no familial history. The brain showed prominent symmetrical white matter changes with greyish discolorization mainly affecting the frontal and parietal lobes, with less involvement of the temporal lobe and only mildly affecting the occipital white matter. Histology revealed deep white matter atrophy with many neuroaxonal spheroids labelled by neurofilament and β-amyloid precursor protein. In addition, scattered inactive demyelinating plaque-like lesions were found in the periventricular areas, brainstem and the cervical spinal cord. This case had typical features of an adult onset leukodystrophy with neuroaxonal spheroids. However, we also demonstrated demyelinating plaque-like lesions, which has not been previously described. The possibility of a demyelinating origin contributing to the changes may be considered in the pathogenesis of this condition.

  18. Supramaximal Stimulus Intensity as a Diagnostic Tool in Chronic Demyelinating Neuropathy

    PubMed Central

    Parker, Vivien; Warman Chardon, Jodi; Mills, Julie; Goldsmith, Claire; Bourque, Pierre R.

    2016-01-01

    Objective. The ability to correctly identify chronic demyelinating neuropathy can have important therapeutic and prognostic significance. The stimulus intensity value required to obtain a supramaximal compound muscle action potential amplitude is a commonly acquired data point that has not been formally assessed as a diagnostic tool in routine nerve conduction studies to identify chronic neuropathies. We postulated that this value was significantly elevated in chronic demyelinating neuropathy. Methods. We retrospectively reviewed electrophysiology laboratory records to compare the stimulus intensity values recorded during median and ulnar motor nerve conduction studies. The groups studied included normal controls (n = 42) and the following diagnostic categories: chronic inflammatory demyelinating neuropathy (CIDP) (n = 20), acquired inflammatory demyelinating neuropathy (AIDP) (n = 13), Charcot Marie Tooth (CMT) type 1 or 4C (n = 15), carpal tunnel syndrome (CTS) (n = 11), and amyotrophic lateral sclerosis (ALS) (n = 18). Results. Supramaximal intensities were significantly higher in patients with CMT (median nerve: 43.4 mA) and CIDP (median nerve: 38.9 mA), whereas values similar to normal controls (median nerve: 25.3 mA) were obtained in ALS, CTS, and AIDP. Conclusions. Supramaximal stimulus intensity may be used as an additional criterion to identify the pathophysiology of neuropathy. We postulate that endoneurial hypertrophic changes may increase electrical impedance and thus the threshold of excitation at nodes of Ranvier. PMID:27413732

  19. Central nervous system demyelination and remyelination in the mouse: an ultrastructural study of cuprizone toxicity.

    PubMed

    Ludwin, S K

    1978-12-01

    Male weanling mice (Biobreeding Laboratories) exposed to the drug Cuprizone (biscyclohexanone, oxaldihydrazone) in the diet for periods of 6 weeks and longer, consistently showed almost complete demyelination of the superior cerebellar peduncle. The demyelination was primary and followed degeneration of oligodendrocytes and their processes, whereas axons remained intact. After formation of myelinic vacuoles and removal of myelin by macrophages and astrocytes, the axons became invested with astroglial processes. As part of the glial response to demyelination, numerous reactive or immature cells appeared, some of which were identified as being either astrocytic or oligodendrocytic in nature. Some mature oligodendrocytes survived. When allowed to recover on a normal diet, remyelination began within a week, and progressed until all axons were myelinated. The mechanism of remyelination appeared similar to the spiral wrapping mechanism seen in normal development. The myelinating cell in all cases was the mature oligodendrocyte. Sources for these oligodendrocytes include residual surviving oligodendrocytes, differentiation of immature forms, and possibly the perineuronal satellite cell. The sheaths eventually reached a thickness approximately half that of normal development, with a disturbed relationship between myelin thickness and axon diameter. A visual impression of shortened internodal length was obtained. It is concluded that the Cuprizone model is an excellent situation in which to study the cellular mechanisms of demyelination and remyelination.

  20. Multifocal acquired demyelinating sensory and motor neuropathy: the Lewis-Sumner syndrome.

    PubMed

    Saperstein, D S; Amato, A A; Wolfe, G I; Katz, J S; Nations, S P; Jackson, C E; Bryan, W W; Burns, D K; Barohn, R J

    1999-05-01

    We report 11 patients with multifocal acquired demyelinating sensory and motor (MADSAM) neuropathy, defined clinically by a multifocal pattern of motor and sensory loss, with nerve conduction studies showing conduction block and other features of demyelination. The clinical, laboratory, and histological features of these patients were contrasted with those of 16 patients with multifocal motor neuropathy (MMN). Eighty-two percent of MADSAM neuropathy patients had elevated protein concentrations in the cerebrospinal fluid, compared with 9% of the MMN patients (P < 0.001). No MADSAM neuropathy patient had elevated anti-GM1 antibody titers, compared with 56% of MMN patients (P < 0.01). In contrast to the subtle abnormalities described for MMN, MADSAM neuropathy patients had prominent demyelination on sensory nerve biopsies. Response to intravenous immunoglobulin treatment was similar in both groups (P = 1.0). Multifocal motor neuropathy patients typically do not respond to prednisone, but 3 of 6 MADSAM neuropathy patients improved with prednisone. MADSAM neuropathy more closely resembles chronic inflammatory demyelinating polyneuropathy and probably represents an asymmetrical variant. Given their different clinical patterns and responses to treatment, it is important to distinguish between MADSAM neuropathy and MMN.

  1. Electrophysiological features of inherited demyelinating neuropathies: A reappraisal in the era of molecular diagnosis.

    PubMed

    Lewis, R A; Sumner, A J; Shy, M E

    2000-10-01

    The observation that inherited demyelinating neuropathies have uniform conduction slowing and that acquired disorders have nonuniform or multifocal slowing was made prior to the identification of mutations in myelin-specific genes which cause many of the inherited disorders involving peripheral nerve myelin. It is now clear that the electrophysiological aspects of these disorders are more complex than previously realized. Specifically, certain mutations appear to induce nonuniform slowing of conduction which resemble the findings in acquired demyelinating neuropathies. It is clinically important to recognize the different electrodiagnostic patterns of the various inherited demyelinating neuropathies. In addition, an understanding of the relationship between mutations of specific genes and their associated neurophysiological findings is likely to facilitate understanding of the role of these myelin proteins in peripheral nerve function and of how abnormalities in myelin proteins lead to neuropathy. We therefore review the current information on the electrophysiological features of the inherited demyelinating neuropathies in hopes of clarifying their electrodiagnostic features and to shed light on the physiological consequences of the different genetic mutations.

  2. Marek’s disease virus genomics

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Marek’s disease virus (MDV) is one of the most oncogenic herpesviruses known and induces a rapid onset T-cell lymphoma and demyelinating disease in chickens. It represents the first of three neoplastic diseases (including hepatocellular carcinoma: hepatitis B virus; and cervical carcinoma: human pap...

  3. Quinone Induced Activation of Keap1/Nrf2 Signaling by Aspirin Prodrugs Masquerading as Nitric Oxide

    PubMed Central

    Dunlap, Tareisha; Piyankarage, Sujeewa C.; Wijewickrama, Gihani T.; Abdul-Hay, Samer; Vanni, Michael; Litosh, Vladislav; Luo, Jia; Thatcher, Gregory R. J.

    2013-01-01

    The promising therapeutic potential of the NO-donating hybrid aspirin prodrugs (NO-ASA), includes induction of chemopreventive mechanisms, and has been reported in almost 100 publications. One example, NCX-4040 (pNO-ASA), is bioactivated by esterase to a quinone methide (QM) electrophile. In cell cultures, pNO-ASA and QM-donating X-ASA prodrugs that cannot release NO rapidly depleted intracellular GSH and caused DNA damage; however, induction of Nrf2 signaling elicited cellular defense mechanisms including upregulation of NAD(P)H:quinone oxidoreductase-1 (NQO1) and glutamate-cysteine ligase (GCL). In HepG2 cells, the “NO-specific” 4,5-diaminofluorescein reporter, DAF-DA, responded to NO-ASA and X-ASA, with QM-induced oxidative stress masquerading as NO. LC-MS/MS analysis demonstrated efficient alkylation of Cys residues of proteins including glutathione-S-transferase-P1 (GST-P1) and Kelch-like ECH-associated protein 1 (Keap1). Evidence was obtained for alkylation of Keap1 Cys residues associated with Nrf2 translocation to the nucleus, nuclear translocation of Nrf2, activation of antioxidant response element (ARE), and upregulation of cytoprotective target genes. At least in cell culture, pNO-ASA acts as a QM-donor, bioactivated by cellular esterase activity to release salicylates, NO3−, and an electrophilic QM. Finally, two novel aspirin prodrugs were synthesized, both potent activators of ARE, designed to release only the QM and salicylates on bioactivation. Current interest in electrophilic drugs acting via Nrf2 signaling suggests that QM-donating hybrid drugs can be designed as informative chemical probes in drug discovery. PMID:23035985

  4. Prevention of autoimmune demyelination in non-human primates by a cAMP-specific phosphodiesterase inhibitor.

    PubMed Central

    Genain, C P; Roberts, T; Davis, R L; Nguyen, M H; Uccelli, A; Faulds, D; Li, Y; Hedgpeth, J; Hauser, S L

    1995-01-01

    Experimental allergic encephalomyelitis (EAE) is an autoimmune disease of the central nervous system that serves as a model for the human disease multiple sclerosis. We evaluated rolipram, a type IV phosphodiesterase inhibitor, for its efficacy in preventing EAE in the common marmoset Callithrix jacchus. In a blinded experimental design, clinical signs of EAE developed within 17 days of immunization with human white matter in two placebo-treated animals but in none of three monkeys that received rolipram (10 mg/kg s.c. every other day) beginning 1 week after immunization. In controls, signs of EAE were associated with development of cerebrospinal fluid pleocytosis and cerebral MRI abnormalities. In the treatment group, there was sustained protection from clinical EAE, transient cerebrospinal fluid pleocytosis in only one of three animals, no MRI abnormality, and marked reduction in histopathologic findings. Rolipram-treated and control animals equally developed circulating antibodies to myelin basic protein. Thus, inhibition of type IV phosphodiesterase, initiated after sensitization to central nervous system antigens, protected against autoimmune demyelinating disease. Images Fig. 1 Fig. 3 Fig. 4 Fig. 5 PMID:7536938

  5. Androstenediol Reduces Demyelination-Induced Axonopathy in the Rat Corpus Callosum: Impact on Microglial Polarization

    PubMed Central

    Kalakh, Samah; Mouihate, Abdeslam

    2017-01-01

    Aims: We have previously shown that the neurosteroid androstenediol (ADIOL) promotes remyelination following gliotoxin-induced demyelination. However, the impact of this ADIOL on axonal recovery is not yet known. In the present study, we investigated the impact of ADIOL on axonal integrity following a focal demyelination in the corpus callosum. Methods: A 2 μl solution of either ethidium bromide (EB; 0.04%) or pyrogen-free saline were stereotaxically injected into the corpus callosum of Sprague Dawley rats. Each of these two rat groups was divided into two subgroups and received daily subcutaneous injections of either ADIOL (5 mg/kg) or vehicle. The brains were collected at 2, 7 and 14 days post-stereotaxic injection. Immunofluorescent staining was used to explore the impact of ADIOL on axonal integrity (neurofilament (NF)-M) and microglial activation (ionized calcium binding adapter molecule 1, Iba1). The inducible nitric oxide synthase (iNOS) and arginase-1 (arg-1), two major markers of microglial polarization towards the proinflammatory M1 and the regulatory M2 phenotypes respectively, were monitored using western blot. Results: ADIOL increased the density of NF fibers and decreased the extent of axonal damage in the vicinity of the demyelination lesion. ADIOL-induced decrease in axonal damage was manifested by decreased number of axonal spheroids at both 2 and 7 days post-demyelination insult. This reduced axonopathy was associated with decreased expression of iNOS and enhanced expression of arg-1 during the acute phase. Conclusion: These data strongly suggest that ADIOL reduces demyelination-induced axonal damage, likely by dampening the local inflammatory response in the white matter and shifting microglial polarization towards a reparative mode. PMID:28280460

  6. Restless Leg Syndrome in Different Types of Demyelinating Neuropathies: A Single-Center Pilot Study

    PubMed Central

    Luigetti, Marco; Del Grande, Alessandra; Testani, Elisa; Bisogni, Giulia; Losurdo, Anna; Giannantoni, Nadia Mariagrazia; Mazza, Salvatore; Sabatelli, Mario; Della Marca, Giacomo

    2013-01-01

    Objective: to determine the prevalence of restless legs syndrome (RLS) in a cohort of patients with demyelinating neuropathies. Methods: Patients were retrospectively recruited from our cohort of different forms of demyelinating neuropathies, including chronic inflammatory demyelinating neuropathy (CIDP), Charcot-Marie-Tooth 1A (CMT1A), and hereditary neuropathy with liability to pressure palsies (HNPP) referred to our Department of Neurology in a 10-year period. The validated 4-item RLS questionnaire was used for diagnosis of RLS. All patients with RLS who fulfilled criteria underwent a suggested immobilization test to confirm the diagnosis. A group of outpatients referred to the sleep disorders unit and data from published literature were used as controls. Results: Prevalence of RLS in demyelinating neuropathy group was higher than prevalence observed in control population (p = 0.0142) or in the literature data (p = 0.0007). In particular, in comparison with both control population and literature data, prevalence of RLS was higher in CIDP group (p = 0.0266 and p = 0.0063, respectively) and in CMT1A group (p = 0.0312 and p = 0.0105, respectively), but not in HNPP (p = 1.000 and p = 0.9320, respectively). Conclusions: our study confirms a high prevalence of RLS in inflammatory neuropathies as CIDP and, among inherited neuropathies, in CMT1A but not in HNPP. Considering that this is only a small cohort from a single-center retrospective experience, the link between RLS and neuropathy remains uncertain, and larger multicenter studies are probably needed to clarify the real meaning of the association between RLS and neuropathy. Citation: Luigetti M; Del Grande A; Testani E; Bisogni G; Losurdo A; Giannantoni NM; Mazza S; Sabatelli M; Della Marca G. Restless leg syndrome in different types of demyelinating neuropathies: a single-center pilot study. J Clin Sleep Med 2013;9(9):945-949. PMID:23997707

  7. Poly(lactic-co-glycolic) acid microspheres encapsulated in Pluronic F-127 prolong hirudin delivery and improve functional recovery from a demyelination lesion.

    PubMed

    Sellers, Drew L; Kim, Tae Hee; Mount, Christopher W; Pun, Suzie H; Horner, Philip J

    2014-10-01

    Components of the blood have been proposed as potential therapeutic targets for improving cellular regeneration after injury and neurodegenerative disease. In this work, thrombin is shown to increase endogenous neural progenitor proliferation in the intact murine spinal cord. A local injection of heparin before a spinal cord injury reduces cell proliferation and astrogliogenesis associated with scarring. We sought to create depot-formulations of PLGA microsphere and Pluronic F-127 for sustained local delivery of two thrombin inhibitors, heparin and hirudin. Each hydrogel depot-formulation showed delayed drug release compared to microspheres or hydrogel alone. Animals with a lateral demyelination lesion showed a reduction in CD68+ macrophages when treated with hirudin-loaded PLGA/F-127 gels compared to control and heparin-treated animals. Moreover, hirudin-loaded materials showed an accelerated recovery in coordinated stepping and increased oligodendrocyte densities. Together, these data demonstrate that controlled delivery of hirudin accelerates functional recovery from a demyelination lesion in the spinal cord.

  8. Poly(lactic-co-glycolic) acid microspheres encapsulated in Pluronic F-127 prolong Hirudin delivery and improve functional recovery from a demyelination lesion

    PubMed Central

    Sellers, Drew L.; Kim, Tae Hee; Mount, Christopher W.; Pun, Suzie H; Horner, Philip J.

    2014-01-01

    Components of the blood have been proposed as potential therapeutic targets for improving cellular regeneration after injury and neurodegenerative disease. In this work, thrombin is shown to increase endogenous neural progenitor proliferation in the intact murine spinal cord. A local injection of heparin before a spinal cord injury reduces cell proliferation and astrogliogenesis associated with scarring. We sought to create depot-formulations of PLGA microsphere and Pluronic F-127 for sustained local delivery of two thrombin inhibitors, heparin and hirudin. Each hydrogel depot-formulation showed delayed drug release compared to microspheres or hydrogel alone. Animals with a lateral demyelination lesion showed a reduction in CD68+ macrophages when treated with hirudin-loaded PLGA/F-127 gels compared to control and heparin-treated animals. Moreover, hirudin-loaded materials showed an accelerated recovery in coordinated stepping and increased oligodendrocyte densities. Together, these data demonstrate that controlled delivery of hirudin accelerates functional recovery from a demyelination lesion in the spinal cord. PMID:25064804

  9. Possible induction of acute disseminated encephalomyelitis (ADEM)-like demyelinating illness by intrathecal mesenchymal stem cell injection.

    PubMed

    Kishk, Nirmeen A; Abokrysha, Noha T; Gabr, Hala

    2013-02-01

    We report a 27-year-old woman with an episode of encephalitis and optic neuritis, followed by autologous bone marrow mesenchymal stem cell transplants and possible induction of acute disseminated encephalomyelitis-like demyelinating illness.

  10. The masquerade game: marine mimicry adaptation between egg-cowries and octocorals

    PubMed Central

    Fuentes-Pardo, Angela P.; Ní Almhain, Íde; Ardila-Espitia, Néstor E.; Cantera-Kintz, Jaime; Forero-Shelton, Manu

    2016-01-01

    system comprised background-matching mimicry, of the masquerade type, between egg-cowries (Simnia/Simnialena) and octocorals (Pacifigorgia/Eugorgia/Leptogorgia). We observed mimicry mismatches related to fitness trade-offs, such as reproductive aggregations vs. vulnerability against predators. Despite the general assumption that coevolution of mimicry involves speciation, egg-cowries with different hosts and colorations comprise the same lineages. Consequently, we infer that there would be significant tradeoffs between mimicry and the pursuit of reproductive aggregations in egg-cowries. The findings of this study not only contribute to the understanding of the evolution of mimicry in egg-cowries, a poorly studied group of marine gastropods, but also to the development of a new biologically meaningful board game that could be implemented as a learning tool. PMID:27547514

  11. The masquerade game: marine mimicry adaptation between egg-cowries and octocorals.

    PubMed

    Sánchez, Juan A; Fuentes-Pardo, Angela P; Ní Almhain, Íde; Ardila-Espitia, Néstor E; Cantera-Kintz, Jaime; Forero-Shelton, Manu

    2016-01-01

    system comprised background-matching mimicry, of the masquerade type, between egg-cowries (Simnia/Simnialena) and octocorals (Pacifigorgia/Eugorgia/Leptogorgia). We observed mimicry mismatches related to fitness trade-offs, such as reproductive aggregations vs. vulnerability against predators. Despite the general assumption that coevolution of mimicry involves speciation, egg-cowries with different hosts and colorations comprise the same lineages. Consequently, we infer that there would be significant tradeoffs between mimicry and the pursuit of reproductive aggregations in egg-cowries. The findings of this study not only contribute to the understanding of the evolution of mimicry in egg-cowries, a poorly studied group of marine gastropods, but also to the development of a new biologically meaningful board game that could be implemented as a learning tool.

  12. Locked-in syndrome after basilary artery thrombosis by mucormycosis masquerading as meningoencephalitis in a lymphoma patient.

    PubMed

    Maffini, Fausto; Cocorocchio, Emilia; Pruneri, Giancarlo; Bonomo, Guido; Peccatori, Fedro; Chiapparini, Laura; Vincenzo, Silvia Di; Martinelli, Giovanni; Viale, Giuseppe

    2013-01-01

    Locked-in syndrome is a rare clinical syndrome due to basilary artery thrombosis generally associated with trauma, vascular, or cardiac malformation. It can present as various types of clinical evolution and occasionally masquerades as other pathological conditions, such as infective meningoencephalitis. These complications are the cause of diagnostic delay, if not promptly recognised, followed by patient death. We report the case of a 42-year-old female with a systemic B and cutaneous T-cell non-Hodgkin's lymphoma, with a severe neutropenia lasting over a year, who eventually developed a rapid and fatal fungal mucormycosis sepsis following a skin infection on her right arm, associated with locked-in syndrome and meningoencephalitis.

  13. Erythromelalgia-like presentation of chronic acquired demyelinating polyneuropathy in a setting of past alcohol abuse.

    PubMed

    Chuquilin, Miguel; Dhand, Upinder K

    2016-02-01

    Erythromelalgia may be primary or secondary to an underlying medical condition. Association with small fiber neuropathy and axonal large fiber peripheral neuropathy has been described. Erythromelalgia in the setting of acquired demyelinating neuropathy has not been reported. We report a 52-year-old woman with severe erythromelalgia, pain and burning, progressive weakness, hyporeflexia and distal pan-sensory deficits. Cerebrospinal fluid protein was 219 mg/dL. Nerve conduction study revealed extreme (ten-fold) prolongation of distal motor latencies, markedly slow motor nerve conduction, reduced terminal latency index, reduced distal compound muscle action potential (CMAP) amplitude, possible conduction blocks, and distal denervation. Treatment with intravenous immunoglobulin, prednisone and azathioprine resulted in marked clinical and electrophysiological improvement. Our patient fulfills the diagnostic criteria for chronic inflammatory demyelinating polyneuropathy (CIDP); however, the unique electrodiagnostic features and presentation with erythromelalgia may represent a CIDP variant or a novel dysimmune neuropathy, or may partly be related to neurotoxic effects of prior alcohol abuse.

  14. Effect of noscapine and vincristine combination on demyelination and cell proliferation in vitro.

    PubMed

    Hiser, Laree; Herrington, Betty; Lobert, Sharon

    2008-08-01

    Peripheral neuropathy is a common, dose-limiting side effect of vincristine, a frontline therapy for acute lymphoblastic leukemia. Combination chemotherapy that reduces the neurotoxicity without compromising the efficacy of vincristine would improve patient outcomes. We performed in vitro studies using a combination of microtubule-binding antimitotics, noscapine and vincristine. In cell cultures containing neurons, astrocytes, and oligodendrocytes, vincristine caused demyelination as shown by transmission electron microscopy. A combination of vincristine and noscapine protected against demyelination. Human acute lymphoblastic and acute myelogenous leukemia cell lines CCRF-CEM and HL-60, respectively, were used to determine the antiproliferative effect of this novel drug combination. Vincristine and noscapine decreased cell proliferation with IC(50) concentrations of 1 nM and 20 microM, respectively. Analysis of dose-effect relationships using isobolograms and combination indices demonstrated that noscapine acts synergistically with vincristine. Thus, noscapine is a promising candidate for use with vincristine to decrease neurotoxicity and enhance antineoplastic effectiveness.

  15. Enhanced adenoviral gene delivery to motor and dorsal root ganglion neurons following injection into demyelinated peripheral nerves.

    PubMed

    Zhang, Yongjie; Zheng, Yiyan; Zhang, Yi Ping; Shields, Lisa B E; Hu, Xiaoling; Yu, Panpan; Burke, Darlene A; Wang, Heming; Jun, Cai; Byers, Jonathan; Whittemore, Scott R; Shields, Christopher B

    2010-08-15

    Injection of viral vectors into peripheral nerves may transfer specific genes into their dorsal root ganglion (DRG) neurons and motoneurons. However, myelin sheaths of peripheral axons block the entry of viral particles into nerves. We studied whether mild, transient peripheral nerve demyelination prior to intraneural viral vector injection would enhance gene transfer to target DRG neurons and motoneurons. The right sciatic nerve of C57BL/6 mice was focally demyelinated with 1% lysolecithin, and the left sciatic nerve was similarly injected with saline (control). Five days after demyelination, 0.5 microl of Ad5-GFP was injected into both sciatic nerves at the site of previous injection. The effectiveness of gene transfer was evaluated by counting GFP(+) neurons in the DRGs and ventral horns. After peripheral nerve demyelination, there was a fivefold increase in the number of infected DRG neurons and almost a 15-fold increase in the number of infected motoneurons compared with the control, nondemyelinated side. Focal demyelination reduced the myelin sheath barrier, allowing greater virus-axon contact. Increased CXADR expression on the demyelinated axons facilitated axoplasmic viral entry. No animals sustained any prolonged neurological deficits. Increased gene delivery into DRG neurons and motoneurons may provide effective treatment for amyotrophic lateral sclerosis, pain, and spinal cord injury.

  16. MHC II expression in the CNS after long-term demyelination

    SciTech Connect

    Cannella, B.; Aquino, D.A.; Raine, C.S.

    1995-07-01

    The ability of chronically demyelinated central nervous system (CNS) tissue to express major histocompatibility complex (MHC) class II molecules has been measured in mouse spinal cord cultures exposed for 1 and 3 weeks to demyelinating anti-white matter (WM) serum. From previous studies, It was known that after 3 weeks of demyelination in vitro, such cultures are incapable of remyelination. In the present report, MHC II levels were evaluated by immunocytochemistry and by Western and Northern blots. The results have shown that after both 1 and 3 weeks of exposure to myelinotoxic anti-WM serum, the cultures retained the ability to express MHC II and this could be further upregulated by incubation with interferon {gamma} (IFN{gamma}). Control groups showed increased expression of MHC II with age. By immunocytochemistry, all groups of cultures expressed high levels of MHC II and all groups showed upregulation after IFN{gamma} treatment. Anti-WM-treated cultures demonstrated slightly higher levels of MHC II than controls. Morphologically, the MHC II expression was associated with the surface of astrocytes. Semiquantitative analysis by Western blotting confirmed the increase in class II MHC expression in the long-term treated cultures after IFN{gamma} exposure, revealing no differences between anti-WM-treated and complement-treated cultures. This was also supported by Northern blotting which showed similar mRNA levels in both groups. These findings suggest that long-term demyelinated CNS tissue still possesses the ability to interact with CD4{sup +} T cells, observations of significance to the expansion of the chronic multiple sclerosis lesion. 50 refs., 6 figs., 2 tabs.

  17. Functional consequences of ethidium bromide demyelination of the mouse ventral spinal cord

    PubMed Central

    Kuypers, Nicholas J.; James, Kurtis T.; Enzmann, Gaby U.; Magnuson, David S.K.; Whittemore, Scott R.

    2013-01-01

    Ethidium bromide (EB) has been extensively used in the rat as a model of spinal cord demyelination. However, this lesion has not been addressed in the adult mouse, a model with unlimited genetic potential. Here we characterize behavioral function, inflammation, myelin status and axonal viability following bilateral injection of 0.20 mg/mL ethidium bromide or saline into the ventral white matter (VWM) of female C57Bl/6 mice. EB-induced VWM demyelination significantly reduced spared VWM and Basso Mouse Scale (BMS) scores persisting out to 2 months. Chronic hindlimb dysfunction was accompanied by a persistent inflammatory response (demonstrated by CD45+ immunofluorescence) and axonal loss (demonstrated by NF-M immunofluorescence and electron microscopy; EM). These cellular responses differ from the rat where inflammation resolves by 3–4 weeks and axon loss is minimal following EB demyelination. As these data suggest that EB-injection in the mouse spinal cord is a non-remyelinating lesion, we sought to ask whether wheel running could promote recovery by enhancing plasticity of local lumbar circuitry independent of remyelination. This did not occur as BMS and Treadscan® assessment revealed no significant effect of wheel running on recovery. However, this study defines the importance of descending ventral motor pathways to locomotor function in the mouse as VWM loss results in a chronic hindlimb deficit. PMID:23466931

  18. Progesterone and nestorone promote myelin regeneration in chronic demyelinating lesions of corpus callosum and cerebral cortex.

    PubMed

    El-Etr, Martine; Rame, Marion; Boucher, Celine; Ghoumari, Abdel M; Kumar, Narender; Liere, Philippe; Pianos, Antoine; Schumacher, Michael; Sitruk-Ware, Regine

    2015-01-01

    Multiple Sclerosis affects mainly women and consists in intermittent or chronic damages to the myelin sheaths, focal inflammation, and axonal degeneration. Current therapies are limited to immunomodulators and antiinflammatory drugs, but there is no efficient treatment for stimulating the endogenous capacity of myelin repair. Progesterone and synthetic progestins have been shown in animal models of demyelination to attenuate myelin loss, reduce clinical symptoms severity, modulate inflammatory responses and partially reverse the age-dependent decline in remyelination. Moreover, progesterone has been demonstrated to promote myelin formation in organotypic cultures of cerebellar slices. In the present study, we show that progesterone and the synthetic 19-nor-progesterone derivative Nestorone® promote the repair of severe chronic demyelinating lesions induced by feeding cuprizone to female mice for up to 12 weeks. Progesterone and Nestorone increase the density of NG2(+) oligodendrocyte progenitor cells and CA II(+) mature oligodendrocytes and enhance the formation of myelin basic protein (MBP)- and proteolipid protein (PLP)-immunoreactive myelin. However, while demyelination in response to cuprizone was less marked in corpus callosum than in cerebral cortex, remyelination appeared earlier in the former. The remyelinating effect of progesterone was progesterone receptor (PR)-dependent, as it was absent in PR-knockout mice. Progesterone and Nestorone also decreased (but did not suppress) neuroinflammatory responses, specifically astrocyte and microglial cell activation. Therefore, some progestogens are promising therapeutic candidates for promoting the regeneration of myelin.

  19. Accelerated remyelination during inflammatory demyelination prevents axonal loss and improves functional recovery

    PubMed Central

    Mei, Feng; Lehmann-Horn, Klaus; Shen, Yun-An A; Rankin, Kelsey A; Stebbins, Karin J; Lorrain, Daniel S; Pekarek, Kara; A Sagan, Sharon; Xiao, Lan; Teuscher, Cory; von Büdingen, H-Christian; Wess, Jürgen; Lawrence, J Josh; Green, Ari J; Fancy, Stephen PJ; Zamvil, Scott S; Chan, Jonah R

    2016-01-01

    Demyelination in MS disrupts nerve signals and contributes to axon degeneration. While remyelination promises to restore lost function, it remains unclear whether remyelination will prevent axonal loss. Inflammatory demyelination is accompanied by significant neuronal loss in the experimental autoimmune encephalomyelitis (EAE) mouse model and evidence for remyelination in this model is complicated by ongoing inflammation, degeneration and possible remyelination. Demonstrating the functional significance of remyelination necessitates selectively altering the timing of remyelination relative to inflammation and degeneration. We demonstrate accelerated remyelination after EAE induction by direct lineage analysis and hypothesize that newly formed myelin remains stable at the height of inflammation due in part to the absence of MOG expression in immature myelin. Oligodendroglial-specific genetic ablation of the M1 muscarinic receptor, a potent negative regulator of oligodendrocyte differentiation and myelination, results in accelerated remyelination, preventing axonal loss and improving functional recovery. Together our findings demonstrate that accelerated remyelination supports axonal integrity and neuronal function after inflammatory demyelination. DOI: http://dx.doi.org/10.7554/eLife.18246.001 PMID:27671734

  20. The Subventricular Zone Is Able to Respond to a Demyelinating Lesion After Localized Radiation

    PubMed Central

    Capilla-Gonzalez, Vivian; Guerrero-Cazares, Hugo; Bonsu, Janice M.; Gonzalez-Perez, Oscar; Achanta, Pragathi; Wong, John; Garcia-Verdugo, Jose Manuel; Quiñones-Hinojosa, Alfredo

    2016-01-01

    Radiation is a common tool in the treatment of brain tumors that induces neurological deficits as a side effect. Some of these deficits appear to be related to the impact of radiation on the neurogenic niches, producing a drastic decrease in the proliferative capacity of these regions. In the adult mammalian brain, the subventricular zone (SVZ) of the lateral ventricles is the main neurogenic niche. Neural stem/precursor cells (NSCs) within the SVZ play an important role in brain repair following injuries. However, the irradiated NSCs' ability to respond to damage has not been previously elucidated. In this study, we evaluated the effects of localized radiation on the SVZ ability to respond to a lysolecithin-induced demyelination of the striatum. We demonstrated that the proliferation rate of the irradiated SVZ was increased after brain damage and that residual NSCs were reactivated. The irradiated SVZ had an expansion of doublecortin positive cells that appeared to migrate from the lateral ventricles toward the demyelinated striatum, where newly generated oligodendrocytes were found. In addition, in the absence of demyelinating damage, remaining cells in the irradiated SVZ appeared to repopulate the neurogenic niche a year post-radiation. These findings support the hypothesis that NSCs are radioresistant and can respond to a brain injury, recovering the neurogenic niche. A more complete understanding of the effects that localized radiation has on the SVZ may lead to improvement of the current protocols used in the radiotherapy of cancer. PMID:24038623

  1. Action potential characteristics of demyelinated rat sciatic nerve following application of 4-aminopyridine.

    PubMed

    Targ, E F; Kocsis, J D

    1986-01-15

    The sciatic nerves of rats were demyelinated by microinjection of lysophosphatidylcholine. A variety of abnormalities such as conduction slowing and block were present. Application of the potassium channel blocker 4-aminopyridine (4-AP) to the lesion site, led to an increase in area of the compound action potential recorded across the site of demyelination. Single axon recordings revealed three types of changes that may account for the 4-AP-induced increase in the compound response. One group showed broadening of the action potential. Other axons showed hyperexcitability following 4-AP, as manifest by spontaneous firing and multiple spike discharge following a single stimulus. In some of the axons studied, 4-AP led to overcoming of conduction block. Although many axons showed increased excitability properties in the presence of 4-AP, the frequency-following ability of the axons was reduced, and the absolute refractory period of the axons was increased. These results indicate that pharmacological blockade of potassium channels with 4-AP not only leads to action potential broadening in demyelinated axons, but to a variety of excitability changes. These heterogeneous effects of 4-AP should be considered in the rationale for its clinical use.

  2. Quantifying the early stages of remyelination following cuprizone-induced demyelination.

    PubMed

    Stidworthy, Mark F; Genoud, Stephane; Suter, Ueli; Mantei, Ned; Franklin, Robin J M

    2003-07-01

    The demyelinating toxin cuprizone is used increasingly in mouse studies of central nervous system remyelination. The value of this model for such studies depends on an accurate description of its quantifiable features. We therefore investigated histology and ultrastructure during the early oligodendrocyte differentiation phase of remyelination in mice given cuprizone and allowed to recover for 2 weeks. Limiting the dose of cuprizone to 0.2% overcame significant mouse morbidity and weight loss seen with a 0.4% dose, but the distribution of cuprizone-induced demyelination was anatomically variable. The caudal corpus callosum and dorsal hippocampal commissure mostly demyelinated at this dose, but the rostral corpus callosum and rostral cerebellar peduncles did not. This variable response, together with small axon diameters and hence thin myelin sheaths, hindered analysis of the progress of early remyelination. The proportion of myelinated and unmyelinated axons in defined regions followed expected trends, but there was pronounced variation between animals. Furthermore, group mean G ratios did not change as expected during the early stages of remyelination, and regression analysis revealed a complex relationship between axon diameter and myelin sheath thickness during this period. We also noted axonal pathology that persisted for at least 2 weeks after cuprizone withdrawal.

  3. Chronic inflammatory demyelinating polyradiculoneuropathy and variants: where we are and where we should go.

    PubMed

    Nobile-Orazio, Eduardo

    2014-03-01

    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a chronic and often disabling sensory motor neuropathy postulated as caused by an immune attack against peripheral nerve myelin. In addition to a classic sensory–motor polyneuropathy, other phenotypes of CIDP have been described including the Lewis- Sumner syndrome, distal acquired demyelinating symmetric (DADS) neuropathy, pure motor CIDP, pure sensory CIDP including chronic immune sensory polyradiculopathy (CISP), and focal CIDP. These phenotypes are currently considered to be variants of CIDP, even if the possibility that they represent different demyelinating neuropathies cannot be fully excluded considering differences in their response to therapy. Several data support the role of the immune system in the pathogenesis of CIDP even if the precise targets and actors (antibodies and lymphocytes) of this immune response remain uncertain. Recent studies have shown that the therapeutic response may differ in patients with peculiar clinical presentations supporting the hypothesis that different pathogenetic mechanisms may underlie the heterogeneity of CIDP. The majority of patients with CIDP show improvement after immune therapies including corticosteroids, plasma exchange, and high-dose intravenous immunoglobulin (IVIg). It remains unclear why none of the other immune therapies that were reported to be variably effective in other immune disorders proved to be effective also in CIDP.

  4. Two years’ long-term follow up in chronic inflammatory demyelinating polyradiculoneuropathy: efficacy of intravenous immunoglobulin treatment

    PubMed Central

    Ellrichmann, Gisa; Gold, Ralf; Ayzenberg, Ilya; Yoon, Min-Suk; Schneider-Gold, Christiane

    2016-01-01

    Background: Administration of intravenous immunoglobulins (IVIgs) is established for long-term treatment of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Prevention of secondary axonal loss going along with permanent clinical disability and muscular atrophy is a major aim in CIDP therapy. To assess long-term clinical efficacy of IVIg treatment despite heterogenous disease course and variable complaints reported by the patients, long-term electrophysiological monitoring was performed for systematic evaluation of therapeutic efficacy of IVIg. Methods: A total of 21 patients with CIDP treated with IVIg 1 g/kg bodyweight every 3–6 weeks were examined electrophysiologically every 12 months over a period of 2 years. Results: Assessment of clinical symptoms, using the Inflammatory Neuropathy Cause and Treatment (INCAT) and Hughes functional grading score (F-score) revealed improvement of motor and sensory symptoms over a period of 2 years. As electrophysiological results remained stable, IVIg treatment seems to be suitable to prevent axonal loss in CIDP. Conclusions: This study confirms efficacy of IVIg as firstline therapy in CIDP. Doses and frequency of IVIg application should be adapted based on clinical evaluation and analysis of long-term electrophysiological findings. PMID:28382108

  5. The complement system contributes to the pathology of experimental autoimmune encephalomyelitis by triggering demyelination and modifying the antigen-specific T and B cell response.

    PubMed

    Hundgeburth, Lorenz C; Wunsch, Marie; Rovituso, Damiano; Recks, Mascha S; Addicks, Klaus; Lehmann, Paul V; Kuerten, Stefanie

    2013-03-01

    So far, studies of the human autoimmune disease multiple sclerosis (MS) have largely been hampered by the absence of a pathogenic B cell component in its animal model, experimental autoimmune encephalomyelitis (EAE). To overcome this shortcoming, we have previously introduced the myelin basic protein (MBP)-proteolipid protein (PLP) MP4-induced EAE, which is B cell and autoantibody-dependent. Here we show that MP4-immunized wild-type C57BL/6 mice displayed a significantly lower disease incidence when their complement system was transiently depleted by a single injection of cobra venom factor (CVF) prior to immunization. Considering the underlying pathomechanism, our data suggest that the complement system is crucial for MP4-specific antibodies to trigger CNS pathology. Demyelinated lesions in the CNS were colocalized with complement depositions. In addition, B cell deficient JHT mice reconstituted with MP4-reactive serum showed significantly attenuated clinical and histological EAE after depletion of complement by CVF. The complement system was also critically involved in the generation of the MP4-specific T and B cell response: in MP4-immunized wild-type mice treated with CVF the MP4-specific cytokine and antibody response was significantly attenuated compared to untreated wild-type mice. Taken together, we propose two independent mechanisms by which the complement system can contribute to the pathology of autoimmune encephalomyelitis. Our data corroborate the role of complement in triggering antibody-dependent demyelination and antigen-specific T cell immunity and also provide first evidence that the complement system can modify the antigen-specific B cell response in EAE and possibly MS.

  6. Mechanisms of immunological tolerance in central nervous system inflammatory demyelination.

    PubMed

    Mari, Elisabeth R; Moore, Jason N; Zhang, Guang-Xian; Rostami, Abdolmohamad

    2015-08-01

    Multiple sclerosis is a complex autoimmune disease of the central nervous system that results in a disruption of the balance between pro-inflammatory and anti-inflammatory signals in the immune system. Given that central nervous system inflammation can be suppressed by various immunological tolerance mechanisms, immune tolerance has become a focus of research in the attempt to induce long-lasting immune suppression of pathogenic T cells. Mechanisms underlying this tolerance induction include induction of regulatory T cell populations, anergy and the induction of tolerogenic antigen-presenting cells. The intravenous administration of encephalitogenic peptides has been shown to suppress experimental autoimmune encephalomyelitis and induce tolerance by promoting the generation of regulatory T cells and inducing apoptosis of pathogenic T cells. Safe and effective methods of inducing long-lasting immune tolerance are essential for the treatment of multiple sclerosis. By exploring tolerogenic mechanisms, new strategies can be devised to strengthen the regulatory, anti-inflammatory cell populations thereby weakening the pathogenic, pro-inflammatory cell populations.

  7. A new pattern of spinal-cord demyelination in guinea pigs with acute experimental allergic encephalomyelitis mimicking multiple sclerosis.

    PubMed Central

    Colover, J.

    1980-01-01

    A technique is described for producing large demyelinating lesions of the spinal cord in the guinea pig. Guinea pigs were pretreated by immunization with ovalbumin and water-soluble adjuvant (N-acetyl-muramyl L-alanyl D-isoglutamine, MDP) in water-in-oil emulsion (Freund's incomplete adjuvant). They were given a large dose (10 mg) of ovalbumin i.p. one month later. After a few weeks the animals were sensitized with guinea-pig basic protein in Freund's complete adjuvant. Five out of 11 animals developed large, distinctive, sharply demarcated, symmetrical demyelinating lesions within 30 days. These lesions occurred in the dorsal and anterior columns, root entry zones and subpial region of the spinal cord. Histology showed a considerable amount of free lipids. There were also infiltrative lesions of classical experimental allergic encephalomyelitis (EAE) of normal severity in the same animals. The demyelinating lesions resembled those seen in multiple sclerosis in their location and extent in the spinal cord and in the presence of free lipids. Control experiments indicated that pretreatment with ovalbumin/MDP and the second injection of ovalbumin was necessary for all the demyelination; moreover guinea pigs immunized with basic protein in Freund's complete adjuvant or Freund's incomplete adjuvant plus MDP without pretreatment only developed classical EAE with minimal or no demyelination. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 PMID:7426390

  8. Pre-treatment with ebselen and vitamin E modulate acetylcholinesterase activity: interaction with demyelinating agents.

    PubMed

    Mazzanti, Cinthia M; Spanevello, Roselia; Ahmed, Musthaq; Pereira, Luciane B; Gonçalves, Jamile F; Corrêa, Maisa; Schmatz, Roberta; Stefanello, Naiara; Leal, Daniela B R; Mazzanti, Alexandre; Ramos, Adriano T; Martins, Tessie B; Danesi, Cristiane Cademartori; Graça, Dominguita L; Morsch, Vera M; Schetinger, Maria Rosa C

    2009-02-01

    The ethidium bromide (EB) demyelinating model was associated with vitamin E (Vit E) and ebselen (Ebs) treatment to evaluate acetylcholinesterase (AChE) activity in the striatum (ST), hippocampus (HP), cerebral cortex (CC) and erythrocytes. Rats were divided into seven groups: I-Control (saline), II-(canola); III-(Ebs), IV-(Vit E); V-(EB); VI-(EB+Ebs) and VII-(EB+Vit E). At 3 days after the EB injection, AChE activity in the CC and HC was significantly reduced in groups III, IV, V, VI and VII (p<0.05) and in the ST it was reduced in groups III and V (p<0.05) when compared to the control group. At 21 days after the EB injection, AChE activity in the CC was significantly reduced in groups III, IV and V, while in groups VI and VII a significant increase was observed when compared to the control group. In the HC and ST, AChE activity was significantly reduced in groups V, VI and VII when compared to the control group (p<0.05). In the erythrocytes, at 3 days after the EB injection, AChE activity was significantly reduced in groups III, IV, V, VI and VII and at 21 days there was a significant reduction only in groups VI and VII (p<0.05) when compared to the control group. In conclusion, this study demonstrated that Ebs and Vit E interfere with the cholinergic neurotransmission by altering AChE activity in the different brain regions and in the erythrocytes. Furthermore, treatment with Vit E and Ebs protected against the demyelination lesion caused by EB. In this context, we can suggest that ebselen and Vit E should be considered potential therapeutics and scientific tools to be investigated in brain disorders associated with demyelinating events.

  9. Successful treatment of chronic inflammatory demyelinating polyneuropathy (CIDP) in systemic lupus erythematosus (SLE) with oral cyclophosphamide.

    PubMed

    Jasmin, R; Sockalingam, S; Shahrizaila, N; Cheah, T-E; Zain, A A; Goh, K-J

    2012-09-01

    Peripheral neuropathy is a known manifestation of systemic lupus erythematosus. However, the association of primary autoimmune inflammatory neuropathies such as chronic inflammatory demyelinating polyneuropathy (CIDP) with SLE is uncommon. We report a 26-year-old man who simultaneously presented with severe CIDP and photosensitive rash, but was unresponsive to intravenous immunoglobulin infusion and continued to progress. He was found to have underlying SLE and improved with combined corticosteroid and immunosuppressive therapy with oral cyclophosphamide. CIDP with underlying SLE may be more resistant to conventional therapy with IVIG, requiring the addition of other immunosuppressive agents.

  10. Acute-onset chronic inflammatory demyelinating polyneuropathy with focal segmental glomerulosclerosis.

    PubMed

    Quek, Amy May Lin; Soon, Derek; Chan, Yee Cheun; Thamboo, Thomas Paulraj; Yuki, Nobuhiro

    2014-06-15

    Inflammatory neuropathies have been reported to occur in association with nephrotic syndrome. Their underlying immuno-pathogenic mechanisms remain unknown. A 50-year-old woman concurrently presented with acute-onset chronic inflammatory demyelinating polyneuropathy and nephrotic syndrome secondary to focal segmental glomerulosclerosis. Both neuropathy and proteinuria improved after plasma exchange and steroids. Literature review of cases of concurrent inflammatory neuropathies and nephrotic syndrome revealed similar neuro-renal presentations. This neuro-renal condition may be mediated by autoantibodies targeting myelin and podocytes.

  11. Optic Neuritis Incidence is Increased in Spring Months in Patients with Asymptomatic Demyelinating Lesions

    PubMed Central

    Balashov, Konstantin E.; Pal, Gian; Rosenberg, Michael L.

    2010-01-01

    Background Optic neuritis (ON) patients can be divided based on the presence or absence of asymptomatic demyelinating lesions (ADL) on brain MRI. The presence of ADL is associated with an increased risk of progression to clinically-definite multiple sclerosis (CDMS). Methods The clinical data and brain MRI of 110 patients with acute unilateral ON were analyzed. Results Patients with ADL had a significantly higher incidence of ON in spring months as compared to patients with no ADL (p=0.0024). Increased incidence of ON in spring months was seen in patients with ADL whether or not they were diagnosed with CDMS on follow-up. PMID:20142310

  12. A case of pediatric multiple sclerosis presenting with a tumefactive demyelinating lesion.

    PubMed

    Majima, Hisakazu; Ito, Tsuyoshi; Koyama, Norihisa

    2017-02-25

    Pediatric multiple sclerosis accompanied by a tumefactive demyelinating lesion (TDL) is extremely rare. Because it is very difficult to distinguish TDLs from neoplasms, invasive brain biopsies are required for a definitive diagnosis. MR spectroscopy (MRS) without brain biopsy was recently shown diagnostic in some patients with TDLs, based on the elevation of glutamate/glutamine peaks. This report describes the clinical course of a 9-year-old girl with multiple sclerosis following a TDL and discusses the usefulness of MRS and brain biopsies to diagnose TDLs.

  13. Multifocal acquired demyelinating sensory and motor neuropathy presenting as a peripheral nerve tumor.

    PubMed

    Allen, David C; Smallman, Clare A; Mills, Kerry R

    2006-09-01

    A man with multifocal acquired demyelinating sensory and motor neuropathy (MADSAM), or Lewis-Sumner syndrome, presented with a progressive left lumbosacral plexus lesion resembling a neurofibroma. After 7 years he developed a left ulnar nerve lesion with conduction block in its upper segment. Treatment with intravenous immunoglobulin improved the symptoms and signs of both lesions. We conclude that inflammatory neuropathy must be considered in the differential diagnosis of peripheral nerve tumors, and that unifocal lesions may precede multifocal involvement in MADSAM by several years. In addition, we discuss the clinical features in 9 patients attending a specialist peripheral nerve clinic and review the literature.

  14. Overview of the pathogenesis and treatment of chronic inflammatory demyelinating polyneuropathy with intravenous immunoglobulins

    PubMed Central

    Mahdi-Rogers, Mohamed; Rajabally, Yusuf A

    2010-01-01

    Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired heterogeneous disorder of immune origin affecting the peripheral nerves, causing motor weakness and sensory symptoms and signs. The precise pathophysiology of CIDP remains uncertain although B and T cell mechanisms are believed to be implicated. Intravenous immunoglobulins (IVIg) have been shown in a number of trials to be an effective treatment for CIDP. IVIg is thought to exert its immunomodulatory effects by affecting several components of the immune system including B-cells, T-cells, macrophages and complement. This article provides an overview of the pathogenesis of CIDP and of its treatment with IVIg. PMID:20376173

  15. Guillain-Barré syndrome (demyelinating) six weeks after bariatric surgery: A case report and literature review.

    PubMed

    Ishaque, Noman; Khealani, Bhojo A; Shariff, Amir H; Wasay, Muhammad

    2015-01-01

    Obesity is a major health problem worldwide. Bariatric surgery has been increasingly used to manage obesity. Many acute as well as chronic neurological complications have been reported after bariatric surgery including Guillain-Barré syndrome (GBS). An autoimmune process has been postulated as the underlying pathophysiology. Most of the reported cases of GBS after bariatric surgery are of the axonal variety. Here, we report a case of a demyelinating variety of GBS in a young woman who presented with acute onset of progressive weakness and paresthesia of all limbs within six weeks after bariatric surgery. She was treated with intravenous immunoglobulin (IVIG) and rehabilitation. She had complete recovery on follow-up. We believe that onset of acute inflammatory demyelinating polyradiculoneuropathy (AIDP), which is demyelinating variety of GBS, is associated with changes in immune system after bariatric surgery.

  16. Defects of Lipid Synthesis Are Linked to the Age-Dependent Demyelination Caused by Lamin B1 Overexpression

    PubMed Central

    Rolyan, Harshvardhan; Tyurina, Yulia Y.; Hernandez, Marylens; Amoscato, Andrew A.; Sparvero, Louis J.; Nmezi, Bruce C.; Lu, Yue; Estécio, Marcos R. H.; Lin, Kevin; Chen, Junda; He, Rong-Rong; Gong, Pin; Rigatti, Lora H.; Dupree, Jeffrey; Bayır, Hülya; Kagan, Valerian E.; Casaccia, Patrizia

    2015-01-01

    Lamin B1 is a component of the nuclear lamina and plays a critical role in maintaining nuclear architecture, regulating gene expression and modulating chromatin positioning. We have previously shown that LMNB1 gene duplications cause autosomal dominant leukodystrophy (ADLD), a fatal adult onset demyelinating disease. The mechanisms by which increased LMNB1 levels cause ADLD are unclear. To address this, we used a transgenic mouse model where Lamin B1 overexpression is targeted to oligodendrocytes. These mice showed severe vacuolar degeneration of the spinal cord white matter together with marked astrogliosis, microglial infiltration, and secondary axonal damage. Oligodendrocytes in the transgenic mice revealed alterations in histone modifications favoring a transcriptionally repressed state. Chromatin changes were accompanied by reduced expression of genes involved in lipid synthesis pathways, many of which are known to play important roles in myelin regulation and are preferentially expressed in oligodendrocytes. Decreased lipogenic gene expression resulted in a significant reduction in multiple classes of lipids involved in myelin formation. Many of these gene expression changes and lipid alterations were observed even before the onset of the phenotype, suggesting a causal role. Our findings establish, for the first time, a link between LMNB1 and lipid synthesis in oligodendrocytes, and provide a mechanistic framework to explain the age dependence and white matter involvement of the disease phenotype. These results have implications for disease pathogenesis and may also shed light on the regulation of lipid synthesis pathways in myelin maintenance and turnover. SIGNIFICANCE STATEMENT Autosomal dominant leukodystrophy (ADLD) is fatal neurological disorder caused by increased levels of the nuclear protein, Lamin B1. The disease is characterized by an age-dependent loss of myelin, the fatty sheath that covers nerve fibers. We have studied a mouse model where Lamin B

  17. Chronic inflammatory demyelinating polyneuropathy due to the administration of pegylated interferon α-2b: a neuropathology case report.

    PubMed

    Shiga, Kensuke; Tanaka, Eijiroh; Isayama, Reina; Mizuno, Toshiki; Itoh, Kyoko; Nakagawa, Masanori

    2012-01-01

    We report a 35-year-old man who developed weakness in his extremities five months after pegylated interferon α (IFNα)-2b was administered. The serum tumor necrosis factor-α (TNFα) was elevated and nerve conduction studies revealed demyelination both in the distal and intermediate segments. The sural nerve pathology showed mild demyelinating process. The cessation of IFNα and administration of intravenous immunoglobulin improved both his clinical symptoms and the temporal dispersion in motor nerve conduction study. IFNα-induced CIDP is presumably a transient immunological condition that requires immunomodulatory therapy. The elevated serum TNFα may implicate the degree of downstream autoimmunity induced by IFNα.

  18. Osmotic Demyelination Syndrome as the Initial Manifestation of a Hyperosmolar Hyperglycemic State

    PubMed Central

    Rodríguez-Velver, Karla Victoria; Soto-Garcia, Analy J.; Zapata-Rivera, María Azucena; Montes-Villarreal, Juan; Villarreal-Pérez, Jesús Zacarías; Rodríguez-Gutiérrez, René

    2014-01-01

    Osmotic demyelination syndrome (ODS) is a life-threatening demyelinating syndrome. The association of ODS with hyperosmolar hyperglycemic state (HHS) has been seldom reported. The aim of this study was to present and discuss previous cases and the pathophysiological mechanisms involved in ODS secondary to HHS. A 47-year-old man arrived to the emergency room due to generalized tonic-clonic seizures and altered mental status. The patient was lethargic and had a Glasgow coma scale of 11/15, muscle strength was 4/5 in both lower extremities, and deep tendon reflexes were diminished. Glucose was 838 mg/dL; serum sodium and venous blood gas analyses were normal. Urinary and plasma ketones were negative. Brain magnetic resonance revealed increased signal intensity on T2-weighted FLAIR images with restricted diffusion on the medulla and central pons. Supportive therapy was started and during the next 3 weeks the patient progressively regained consciousness and muscle strength and was able to feed himself. At 6-month follow-up, the patient was asymptomatic and MRI showed no residual damage. In conclusion, the association of ODS with HHS is extremely rare. The exact mechanism by which HHS produces ODS still needs to be elucidated, but we favor a rapid hypertonic insult as the most plausible mechanism. PMID:25431711

  19. Paracaspase MALT1 deficiency protects mice from autoimmune-mediated demyelination.

    PubMed

    Mc Guire, Conor; Wieghofer, Peter; Elton, Lynn; Muylaert, David; Prinz, Marco; Beyaert, Rudi; van Loo, Geert

    2013-03-15

    The paracaspase MALT 1 is a major player in lymphocyte activation and proliferation. MALT1 mediates Ag-induced signaling to the transcription factor NF-κB by functioning both as a scaffold protein and cysteine protease. We studied the role of MALT1 in the development of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. MALT1-knockout mice did not develop any clinical symptoms of EAE. In addition, lymphocyte and macrophage infiltration into the spinal cord was absent in MALT1-knockout mice, as were demyelination and proinflammatory gene expression. Adoptive transfer experiments showed that MALT1 deficiency in splenocytes is sufficient for EAE resistance. Moreover, autoreactive T cell activation was severely impaired in MALT1-deficient T cells, suggesting the inability of MALT1-deficient effector T cells to induce demyelinating inflammation in the CNS. Finally, the MALT1 substrates A20 and CYLD were completely processed in wild-type T cells during EAE, which was partially impaired in MALT1-deficient T cells, suggesting a contribution of MALT1 proteolytic activity in T cell activation and EAE development. Together, our data indicate that MALT1 may be an interesting therapeutic target in the treatment of multiple sclerosis.

  20. Osmotic demyelination syndrome as the initial manifestation of a hyperosmolar hyperglycemic state.

    PubMed

    Rodríguez-Velver, Karla Victoria; Soto-Garcia, Analy J; Zapata-Rivera, María Azucena; Montes-Villarreal, Juan; Villarreal-Pérez, Jesús Zacarías; Rodríguez-Gutiérrez, René

    2014-01-01

    Osmotic demyelination syndrome (ODS) is a life-threatening demyelinating syndrome. The association of ODS with hyperosmolar hyperglycemic state (HHS) has been seldom reported. The aim of this study was to present and discuss previous cases and the pathophysiological mechanisms involved in ODS secondary to HHS. A 47-year-old man arrived to the emergency room due to generalized tonic-clonic seizures and altered mental status. The patient was lethargic and had a Glasgow coma scale of 11/15, muscle strength was 4/5 in both lower extremities, and deep tendon reflexes were diminished. Glucose was 838 mg/dL; serum sodium and venous blood gas analyses were normal. Urinary and plasma ketones were negative. Brain magnetic resonance revealed increased signal intensity on T2-weighted FLAIR images with restricted diffusion on the medulla and central pons. Supportive therapy was started and during the next 3 weeks the patient progressively regained consciousness and muscle strength and was able to feed himself. At 6-month follow-up, the patient was asymptomatic and MRI showed no residual damage. In conclusion, the association of ODS with HHS is extremely rare. The exact mechanism by which HHS produces ODS still needs to be elucidated, but we favor a rapid hypertonic insult as the most plausible mechanism.

  1. A diagnosis challenge-L4 nerve root compression as the initial presentation of chronic inflammatory demyelinating polyneuropathy.

    PubMed

    Cojocaru, Inimioara Mihaela; Alexianu, Marilena; Bastian, Alexandra; Sapira, Violeta; Herţea, Cristina; Cojocaru, M

    2012-01-01

    The authors present the case of a 65-year-old woman who was admitted for paraparesis and paresthesias in the inferior limbs. The neurological examination revealed the difficulty in extension of the right foot and of the right toe, accompanied by paresthesias located in the anterolateral area of the right leg, dorsum and plantar area of the foot, the reduction of the right knee jerk, and of the ankle tendon jerk both sides. The vertebro-spinal MRI showed lumbar canal stenosis with L4 intraforaminal compression on the right, and L2-L3 on the left. CSF examination revealed mild increase in protein concentration. The morphological picture of the sural nerve biopsy was compatible with a chronic inflammatory neuropathy and severe muscular lesions of neurogenic origin were observed on right gastrocnemius muscle biopsy. The diagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP) was established. Solu-medrol (0.5 g/d)-5 days, then medrol (prednisolone) was done, followed by improving of the symptomatology. For the relapse of the disease intravenous immunoglobulins (IVIG)-0.4 g/kg/d-5 days was the elective treatment. Six months later she presented a new relapse. IVIG were administered with the remission of the sensitive symptoms. A chronic treatment with medrol was recommended. The diagnosis of L4 disc herniation was obvious in the studied case, but the electroneurographic examination brought extra data for the associated diagnosis of CIDP whose onset was asymmetrical and initially paucisymptomatic. Neither the electroneurographic examination nor the CSF examination were total relevant for CIDP, imposing the sural nerve biopsy. The diagnosis of CIDP involves a team-work composed of neurologist, electroneurophysiologist and neuropathologist.

  2. Peripheral Nerve Ultrasonography in Chronic Inflammatory Demyelinating Polyradiculoneuropathy and Multifocal Motor Neuropathy: Correlations with Clinical and Neurophysiological Data

    PubMed Central

    Merola, Aristide; Rosso, Michela; Romagnolo, Alberto; Peci, Erdita; Cocito, Dario

    2016-01-01

    Objective. This cross-sectional study analyzes the pattern of ultrasound peripheral nerve alterations in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy (MMN) at different stages of functional disability. Material and Methods. 22 CIDP and 10 MMN patients and a group of 70 healthy controls were evaluated with an ultrasound scan of the median, ulnar, peroneal, tibial, and sural nerves. Results were correlated with clinical disability scales and nerve conduction studies. Results. Patients with intermediate functional impairment showed relatively larger cross-sectional areas than subjects with either a milder (p < 0.05) or more severe impairment (p < 0.05), both in CIDP and in MMN. In addition, MMN was associated with greater side-to-side intranerve variability (p < 0.05), while higher cross-sectional areas were observed in CIDP (p < 0.05) and in nerve segments with predominantly demyelinating features (p < 0.05). Higher CSA values were observed in nerves with demyelinating features versus axonal damage (p < 0.05 for CIDP; p < 0.05 for MMN). Discussion and Conclusions. Greater extent of quantitative and qualitative US alterations was observed in patients at intermediate versus higher functional disability and in nerves with demyelinating versus axonal damage. CIDP and MMN showed differential US aspects, with greater side-to-side intranerve variability in MMN and higher cross-sectional areas in CIDP. PMID:27313890

  3. Severity and Patterns of Blood-Nerve Barrier Breakdown in Patients with Chronic Inflammatory Demyelinating Polyradiculoneuropathy: Correlations with Clinical Subtypes

    PubMed Central

    Shimizu, Fumitaka; Sawai, Setsu; Sano, Yasuteru; Beppu, Minako; Misawa, Sonoko; Nishihara, Hideaki; Koga, Michiaki; Kuwabara, Satoshi; Kanda, Takashi

    2014-01-01

    Objective Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is currently classified into clinical subtypes, including typical and atypical forms (multifocal acquired demyelinating sensory and motor neuropathy (MADSAM) and distal acquired demyelinating symmetric neuropathy (DADS)). The aim of this study was to elucidate the patterns and severity of breakdown of the blood-nerve barrier (BNB) in each CIDP subtype. Methods We evaluated the effects of sera obtained from patients with typical CIDP, MADSAM and DADS and control subjects on the expression levels of tight junction proteins and transendothelial electrical resistance (TEER) value in human peripheral nerve microvascular endothelial cells (PnMECs). Results The sera obtained from the patients with the three clinical phenotypes of CIDP decreased the amount of claudin-5 protein levels and TEER values in the PnMECs. In addition, the sera obtained from typical CIDP patients more prominently reduced claudin-5 protein levels and TEER values in the PnMECs than did that obtained from the MADSAM and DADS patients. Furthermore, the severity of BNB disruption after exposure to the sera was associated with higher Hughes grade, lower MRC score, more pronounced slowing of motor nerve conduction in the median nerve and higher frequency of abnormal temporal dispersion. Conclusions Sera derived from typical CIDP patients destroy the BNB more severely than those from MADSAM or DADS patients. The extent of BNB disruption in the setting of CIDP is associated with clinical disability and demyelination in the nerve trunk. These observations may explain the phenotypical differences between CIDP subtypes. PMID:25105500

  4. Calreticulin and other components of endoplasmic reticulum stress in rat and human inflammatory demyelination

    PubMed Central

    2013-01-01

    Background Calreticulin (CRT) is a chaperone protein, which aids correct folding of glycosylated proteins in the endoplasmic reticulum (ER). Under conditions of ER stress, CRT is upregulated and may be displayed on the surface of cells or be secreted. This ‘ecto-CRT’ may activate the innate immune response or it may aid clearance of apoptotic cells. Our and other studies have demonstrated upregulation of ER stress markers CHOP, BiP, ATF4, XBP1 and phosphorylated e-IF2 alpha (p-eIF2 alpha) in biopsy and post-mortem human multiple sclerosis (MS) samples. We extend this work by analysing changes in expression of CRT, BiP, CHOP, XBP1 and p-eIF2 alpha in a rat model of inflammatory demyelination. Demyelination was induced in the spinal cord by intradermal injection of recombinant mouse MOG mixed with incomplete Freund’s adjuvant (IFA) at the base of the tail. Tissue samples were analysed by semi-quantitative scoring of immunohistochemically stained frozen tissue sections. Data generated following sampling of tissue from animals with spinal cord lesions, was compared to that obtained using tissue derived from IFA- or saline-injected controls. CRT present in rat serum and in a cohort of human serum derived from 14 multiple sclerosis patients and 11 healthy controls was measured by ELISA. Results Stained tissue scores revealed significantly (p<0.05) increased amounts of CRT, CHOP and p-eIF2 alpha in the lesion, lesion edge and normal-appearing white matter when compared to controls. CHOP and p-eIF2 alpha were also significantly raised in regions of grey matter and the central canal (p<0.05). Immunofluorescent dual-label staining confirmed expression of these markers in astrocytes, microglia or neurons. Dual staining of rat and human spinal cord lesions with Oil Red O and CRT antibody showed co-localisation of CRT with the rim of myelin fragments. ELISA testing of sera from control and EAE rats demonstrated significant down-regulation (p<0.05) of CRT in the serum of

  5. Tactical decisions for changeable cuttlefish camouflage: visual cues for choosing masquerade are relevant from a greater distance than visual cues used for background matching.

    PubMed

    Buresch, Kendra C; Ulmer, Kimberly M; Cramer, Corinne; McAnulty, Sarah; Davison, William; Mäthger, Lydia M; Hanlon, Roger T

    2015-10-01

    Cuttlefish use multiple camouflage tactics to evade their predators. Two common tactics are background matching (resembling the background to hinder detection) and masquerade (resembling an uninteresting or inanimate object to impede detection or recognition). We investigated how the distance and orientation of visual stimuli affected the choice of these two camouflage tactics. In the current experiments, cuttlefish were presented with three visual cues: 2D horizontal floor, 2D vertical wall, and 3D object. Each was placed at several distances: directly beneath (in a circle whose diameter was one body length (BL); at zero BL [(0BL); i.e., directly beside, but not beneath the cuttlefish]; at 1BL; and at 2BL. Cuttlefish continued to respond to 3D visual cues from a greater distance than to a horizontal or vertical stimulus. It appears that background matching is chosen when visual cues are relevant only in the immediate benthic surroundings. However, for masquerade, objects located multiple body lengths away remained relevant for choice of camouflage.

  6. The EIIIA domain from astrocyte‐derived fibronectin mediates proliferation of oligodendrocyte progenitor cells following CNS demyelination

    PubMed Central

    Stoffels, Josephine M. J.; Hoekstra, Dick; Franklin, Robin J. M.

    2014-01-01

    Central nervous system remyelination by oligodendrocyte progenitor cells (OPCs) ultimately fails in the majority of multiple sclerosis (MS) lesions. Remyelination benefits from transient expression of factors that promote migration and proliferation of OPCs, which may include fibronectin (Fn). Fn is present in demyelinated lesions in two major forms; plasma Fn (pFn), deposited following blood‐brain barrier disruption, and cellular Fn, synthesized by resident glial cells and containing alternatively spliced domains EIIIA and EIIIB. Here, we investigated the distinctive roles that astrocyte‐derived Fn (aFn) and pFn play in remyelination. We used an inducible Cre‐lox recombination strategy to selectively remove pFn, aFn or both from mice, and examined the impact on remyelination of toxin‐induced demyelinated lesions of spinal cord white matter. This approach revealed that astrocytes are a major source of Fn in demyelinated lesions. Furthermore, following aFn conditional knockout, the number of OPCs recruited to the demyelinated lesion decreased significantly, whereas OPC numbers were unaltered following pFn conditional knockout. However, remyelination completed normally following conditional knockout of aFn and pFn. Both the EIIIA and EIIIB domains of aFn were expressed following demyelination, and in vitro assays demonstrated that the EIIIA domain of aFn mediates proliferation of OPCs, but not migration. Therefore, although the EIIIA domain from aFn mediates OPC proliferation, aFn is not essential for successful remyelination. Since previous findings indicated that astrocyte‐derived Fn aggregates in chronic MS lesions inhibit remyelination, aFn removal may benefit therapeutic strategies to promote remyelination in MS. GLIA 2015;63:242–256 PMID:25156142

  7. [Anesthetic management of a Dialysis Patient with Chronic Inflammatory Demyelinating Polyneuropathy].

    PubMed

    Takahashi, Yoshihiro; Hara, Koji; Sata, Takeyoshi

    2015-11-01

    We report the successful management of anesthesia in a 46-year-old male dialysis patient with chronic inflammatory demyelinating polyneuropathy (CIDP). He underwent an osteosynthesis of the ankle joint using general anesthesia combined with epidural anesthesia. The anesthetic concerns in patients with CIDP are the possibility of postoperative respiratory dysfunction due to anesthetics or muscle relaxants and that of postoperative neurological deterioration due to spinal or epidural anesthesia. In this case, sevoflurane (1.5-2%) did not cause respiratory dysfunction postoperatively and muscle relaxant effect of rocuronium was effectively reversed by sugammadex. Epidural anesthesia using ropivacaine (0.2-0.375%) and fentanyl did not worsen the neurological symptoms of CIDP post-operatively.

  8. Office immunotherapy in chronic inflammatory demyelinating polyneuropathy and multifocal motor neuropathy.

    PubMed

    Dyck, Peter J; Taylor, Bruce V; Davies, Jenny L; Mauermann, Michelle L; Litchy, William J; Klein, Christopher J; Dyck, P James B

    2015-10-01

    Intravenous immunoglobulin [IVIg], plasma exchange [PE], and corticosteroids are efficacious treatment in chronic inflammatory demyelinating polyneuropathy [CIDP]. IVIg is effective in multifocal motor neuropathy [MMN]. NIS, NIS-weakness, sum scores of raw amplitudes of motor fiber (CMAPs) amplitudes, and Dyck/Rankin score provided reliable measures to detect and scale abnormality and reflect change; they are therefore ideal for office management of response-based immunotherapy (R-IRx) of CIDP. Using efficacious R-IRx, a large early and late therapeutic response (≥ one-fourth were in remission or had recovered) was demonstrated in CIDP. In MMN only an early improvement with late non-significant worsening was observed. The difference in immunotherapy response supports a fundamental difference between CIDP (immune attack on Schwann cells and myelin) and MMN (attack on nodes of Ranvier and axons).

  9. IVIG regulates BAFF expression in patients with chronic inflammatory demyelinating polyneuropathy (CIDP).

    PubMed

    Ritter, Christian; Förster, Dominik; Albrecht, Philipp; Hartung, Hans-Peter; Kieseier, Bernd C; Lehmann, Helmar C

    2014-09-15

    Recent studies indicate that the cytokine B-cell activating factor (BAFF) is involved in the pathogenesis of chronic inflammatory demyelinating polyneuropathy (CIDP). Intravenous immunoglobulin (IVIg) is standard treatment for CIDP and is known to rapidly modulate increased serum levels of pro-inflammatory cytokines. We evaluated the expression profile of BAFF and its corresponding BAFF-receptor in samples from CIDP patients, focusing on rapid changes before and after IVIg treatment. In CIDP patients BAFF serum concentrations were elevated compared to controls. Treatment with high-dose IVIg restored those elevated BAFF serum levels. Whereas treatment with IVIg did not affect BAFF production in monocytes, antibodies against BAFF could be detected in IVIg preparations, which may explain the short-term decrease of BAFF levels after IVIg treatment. Our data suggest that BAFF plays an important role in the pathogenesis of CIDP and may serve as marker for IVIg treatment response.

  10. Are ERM (ezrin/radixin/moesin) proteins targets for autoantibodies in demyelinating neuropathies?

    PubMed

    Miyaji, Kazuki; Shahrizaila, Nortina; Umapathi, Thirugnanam; Chan, Yee-Cheun; Hirata, Koichi; Yuki, Nobuhiro

    2014-11-01

    Ezrin, radixin and moesin, which are strongly expressed in the Schwann cell microvilli, are putative targets for autoantibodies in acute or chronic inflammatory demyelinating polyneuropathy (AIDP or CIDP). An association between anti-moesin IgG antibodies and cytomegalovirus-related AIDP has been postulated. None of 41 AIDP patients, including 8 cytomegalovirus-related AIDP patients, and 23 CIDP had IgG or IgM antibodies to ezrin, radixin and moesin; whereas, one patient with cytomegalovirus-related AIDP had anti-ezrin IgM antibodies. Ezrin, radixin and moesin are unlikely targets for autoantibodies in AIDP and CIDP, and the association of anti-moesin antibodies with cytomegalovirus-related AIDP was not confirmed.

  11. Prostacyclin Prevents Pericyte Loss and Demyelination Induced by Lysophosphatidylcholine in the Central Nervous System*

    PubMed Central

    Muramatsu, Rieko; Kuroda, Mariko; Matoba, Ken; Lin, Hsiaoyun; Takahashi, Chisato; Koyama, Yoshihisa; Yamashita, Toshihide

    2015-01-01

    Pericytes play pivotal roles in physiological and pathophysiological conditions in the central nervous system. As pericytes prevent vascular leakage, they can halt neuronal damage stemming from a compromised blood-brain barrier. Therefore, pericytes may be a good target for the treatment of neurodegenerative disorders, although evidence is lacking. In this study, we show that prostacyclin attenuates lysophosphatidylcholine (LPC)-mediated vascular dysfunction through pericyte protection in the adult mouse spinal cord. LPC decreased the number of pericytes in an in vitro blood-brain barrier model, and this decrease was prevented by iloprost treatment, a prostacyclin analog. Intrathecal administration of iloprost attenuated vascular barrier disruption after LPC injection in the mouse spinal cord. Furthermore, iloprost treatment diminished demyelination and motor function deficits in mice injected with LPC. These results support the notion that prostacyclin acts on pericytes to maintain vascular barrier integrity. PMID:25795781

  12. Family with inflammatory demyelinating polyneuropathy and the HNPP 17p12 deletion.

    PubMed

    Korn-Lubetzki, Isabelle; Argov, Zohar; Raas-Rothschild, Annick; Wirguin, Itzchak; Steiner, Israel

    2002-12-01

    Hereditary neuropathy with liability to pressure palsies (HNPP), classically presenting as recurrent focal neuropathies precipitated by trauma or compression, is an autosomal dominant neuropathy due to a deletion at chromosomal locus 17p12. Inflammatory demyelinating polyneuropathy (IDP), a putative autoimmune disorder presenting in an acute (AIDP) or a chronic form (CIDP), has been rarely reported as familial. We present a father and two daughters of Jewish Kurdish origin who developed IDP within 10 years. The unusual familial history led us to reevaluate the diagnosis of IDP, and suggested an autosomal dominant pedigree. DNA analysis identified the deletion typical of HNPP on chromosome 17. Screening for the HNPP deletion in patients with atypical, recurrent, or familial IDP might be warranted.

  13. Chronic Inflammatory Demyelinating Polyneuropathy with Reversible Dementia: A New Clinical Entity?

    PubMed Central

    Samaniego, Jorge

    2013-01-01

    Introduction Classic chronic inflammatory demyelinating polyneuropathy (CIDP), an acquired demyelination of peripheral nerves and nerve roots presents with symmetric motor and sensory involvement, weakness in proximal and distal muscles, globally diminished or absent reflexes, painful dysesthesias, and back pain with no brain involvement. In this case, a highly functional lawyer presents with reversible dementia and motor and sensory symptoms consistent with CIDP. This case may represent a new clinical entity of CIDP with reversible dementia. Case Report A 60-year-old man presented with progressive weakness, and cognitive dysfunction in the form of dementia over the last 8 weeks. Sensory and motor weakness continued to progress affecting upper and lower extremities with both proximal and distal muscle groups to the point where the patient was unable to move without assistance. The patient had word finding difficulty, short-term memory impairment, and was disoriented, despite his comprehension being intact. Initial Montreal Cognitive Assessment (MoCA) was 12/30. Initial neurologic exam was notable for muscle strength 3/5, globally depressed deep tendon reflexes. Lumbar puncture revealed elevated protein with no pleocytosis and no serum paraprotein. EMG/NCS demonstrated mixed sensorimotor axonal and demyelination peripheral polyneuropathy. CIDP was diagnosed based on clinical history according to Koski criteria. He was started on a 5-day treatment of IVIG, after which he had marked cognitive improvement after just one dose and improvement in weakness after the second dose of IVIG. Three weeks after IVIG treatment, the patient's cognitive function was back at baseline with MoCA score 29/30; no further word finding difficulty, and no short term memory impairment. At discharge, the patient's weakness had significantly improved to the point where he was able to walk with only the aid of a walker. His neurologic exam had improved as well as his muscle strength 4/5 and 2

  14. Office Immunotherapy in Chronic Inflammatoryh Demyelinating Polyneuropathy and Multifocal Motor Neuropathy

    PubMed Central

    Dyck, Peter J.; Taylor, Bruce V.; Davies, Jenny L.; Mauermann, Michelle L.; Litchy, William J.; Klein, Christopher J.; Dyck, P. James B.

    2015-01-01

    Background Intravenous immunoglobulin [IVIg], plasma exchange [PE], and corticosteroids are efficacious treatment in chronic inflammatory demyelinating polyneuropathy [CIDP]. IVIg is effective in multifocal motor neuropathy [MMN]. Objective and Methods Results and Conclusions NIS, NIS-weakness, sum scores of raw amplitudes of motor fiber (CMAPs) amplitudes, and Dyck/Rankin score provided reliable measures to detect and scale abnormality and reflect change; they are therefore ideal for office management of response-basedimmunotherapy (R-IRx) of CIDP. Using efficacious R-IRx, a large early and late therapeutic response (≥ one-fourth were in remission or had recovered) was demonstrated in CIDP. In MMN only an early improvement with late non-significant worsening was observed. The difference in immunotherapy response supports a fundamental difference between CIDP (immune attack on Schwann cells and myelin) and MMN (attack on nodes of Ranvier and axons). PMID:25976871

  15. Brain-derived neurotrophic factor deficiency restricts proliferation of oligodendrocyte progenitors following cuprizone-induced demyelination.

    PubMed

    Tsiperson, Vladislav; Huang, Yangyang; Bagayogo, Issa; Song, Yeri; VonDran, Melissa W; DiCicco-Bloom, Emanuel; Dreyfus, Cheryl F

    2015-01-01

    Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family of growth factors that through its neurotrophic tyrosine kinase, receptor, type 2 (TrkB) receptor, increases 5-bromo-2-deoxyuridine incorporation in oligodendrocyte progenitor cells (OPCs) in culture. Roles in vivo are less well understood; however, increases in numbers of OPCs are restricted in BDNF+/- mice following cuprizone-elicited demyelination. Here, we investigate whether these blunted increases in OPCs are associated with changes in proliferation. BDNF+/+ and BDNF+/- mice were fed cuprizone-containing or control feed. To assess effects on OPC numbers, platelet-derived growth factor receptor alpha (PDGFRα)+ or NG2+ cells were counted. To monitor DNA synthesis, 5-ethynyl-2'-deoxyuridine (EdU) was injected intraperitoneally and colocalized with PDGFRα+ cells. Alternatively, proliferating cell nuclear antigen (PCNA) was colocalized with PDGFRα or NG2. Labeling indices were determined in the BDNF+/+ and BDNF+/- animals. After 4 or 5 weeks of control feed, BDNF+/- mice exhibit similar numbers of OPCs compared with BDNF+/+ animals. The labeling indices for EdU and PCNA also were not significantly different, suggesting that neither the DNA synthesis phase (S phase) nor the proliferative pool size was different between genotypes. In contrast, when mice were challenged by cuprizone for 4 or 5 weeks, increases in OPCs observed in BDNF+/+ mice were reduced in the BDNF+/- mice. This difference in elevations in cell number was accompanied by decreases in EdU labeling and PCNA labeling without changes in cell death, indicating a reduction in the DNA synthesis and the proliferative pool. Therefore, levels of BDNF influence the proliferation of OPCs resulting from a demyelinating lesion.

  16. [Chronic inflammatory demyelinating polyneuropathy after treatment with pegylated interferon alpha 2b in a patient with HIV/HCV coinfection: case report].

    PubMed

    Bassetti, Bil Randerson; Trés, Eduardo Sturzeneker; Ciríaco, Jovana Gobbi Marchesi; Pinto Neto, Lauro Ferreira Silva

    2010-01-01

    Chronic inflammatory demyelinating polyneuropathy has a strong association with HIV and HCV infection. A rare association between chronic inflammatory demyelinating polyneuropathy and hepatitis C treatment with pegylated interferon alpha was described recently. We described the first case of chronic inflammatory demyelinating polyneuropathy associated with pegylated interferon alpha 2b in a white man infected with HIV and HCV. The patient recovered completely with the use of intravenous hyperimmune immunoglobulin. Infectologists and hepatologists should be alert regarding this rare and serious association, which requires immediately drug discontinuation and early treatment.

  17. Quinone-induced activation of Keap1/Nrf2 signaling by aspirin prodrugs masquerading as nitric oxide.

    PubMed

    Dunlap, Tareisha; Piyankarage, Sujeewa C; Wijewickrama, Gihani T; Abdul-Hay, Samer; Vanni, Michael; Litosh, Vladislav; Luo, Jia; Thatcher, Gregory R J

    2012-12-17

    The promising therapeutic potential of the NO-donating hybrid aspirin prodrugs (NO-ASA) includes induction of chemopreventive mechanisms and has been reported in almost 100 publications. One example, NCX-4040 (pNO-ASA), is bioactivated by esterase to a quinone methide (QM) electrophile. In cell cultures, pNO-ASA and QM-donating X-ASA prodrugs that cannot release NO rapidly depleted intracellular GSH and caused DNA damage; however, induction of Nrf2 signaling elicited cellular defense mechanisms including upregulation of NAD(P)H:quinone oxidoreductase-1 (NQO1) and glutamate-cysteine ligase (GCL). In HepG2 cells, the "NO-specific" 4,5-diaminofluorescein reporter, DAF-DA, responded to NO-ASA and X-ASA, with QM-induced oxidative stress masquerading as NO. LC-MS/MS analysis demonstrated efficient alkylation of Cys residues of proteins including glutathione-S-transferase-P1 (GST-P1) and Kelch-like ECH-associated protein 1 (Keap1). Evidence was obtained for alkylation of Keap1 Cys residues associated with Nrf2 translocation to the nucleus, nuclear translocation of Nrf2, activation of antioxidant response element (ARE), and upregulation of cytoprotective target genes. At least in cell culture, pNO-ASA acts as a QM donor, bioactivated by cellular esterase activity to release salicylates, NO(3)(-), and an electrophilic QM. Finally, two novel aspirin prodrugs were synthesized, both potent activators of ARE, designed to release only the QM and salicylates on bioactivation. Current interest in electrophilic drugs acting via Nrf2 signaling suggests that QM-donating hybrid drugs can be designed as informative chemical probes in drug discovery.

  18. A case of sacro-coccygeal chordoma masquerading as pilonidal sinus.

    PubMed

    Beattie, G C; Millar, L; Nawroz, I M; Browning, G G

    2000-08-01

    Chordoma is a rare, slow-growing, but locally aggressive malignant tumour derived from the primitive notochord. Pilonidal sinus disease, characterised by communicating granulating natal cleft tracts and abscesses, is a common condition. We report a case of a sacro-coccygeal chordoma diagnosed incidentally on surgical exploration of a case of presumed pilonidal disease.

  19. Primary Esophageal Intramural Squamous Cell Carcinoma Masquerading as a Submucosal Tumor: A Rare Presentation of a Common Disease

    PubMed Central

    Sonthalia, Nikhil; Jain, Samit S.; Surude, Ravindra G.; Pawar, Vinay B.; Udgirkar, Suhas; Rathi, Pravin M.

    2016-01-01

    Esophageal squamous cell carcinoma (ESCC) is the commonest primary malignant esophageal tumor, which typically presents as endoscopically visible surface mucosal ulcerations, irregularities, or polyploidal masses. We here report a rare case of primary ESCC with completely intramural growth under a normal looking intact nondysplastic surface squamous epithelium disguising as a submucosal tumor. Upper gastrointestinal endoscopy-guided mucosal biopsy was negative for malignancy. Endoscopic ultrasound (EUS) revealed a heteroechoic solid mass originating from the muscularis propria of the distal esophagus. Cytological study of EUS-guided fine needle aspiration from the mass was suggestive of squamous cell carcinoma, which was confirmed on immunohistochemistry. There was no evidence of metastatic origin of this tumor or continuous cancer involvement from the surrounding structures, including the head, neck, and lungs on bronchoscopy, computed tomography scan, and positron emission tomography scan. Exclusive intramural squamous cell carcinoma with normal overlying mucosa is an exceedingly rare presentation of primary ESCC with only four cases reported in the literature so far. A high index of suspicion is required by the gastroenterologists and pathologists in diagnosing these cases as these tumors closely mimic the mesenchymal submucosal tumors such as lipoma, leiomyoma, and gastrointestinal stromal tumors. EUS is an indispensable tool in making a preoperative diagnosis and therapeutic decision making. PMID:27721663

  20. Central Nervous System Idiopathic Inflammatory Demyelinating Disorders in South Americans: A Descriptive, Multicenter, Cross-Sectional Study

    PubMed Central

    Papais-Alvarenga, Regina Maria; Vasconcelos, Claudia Cristina Ferreira; Carra, Adriana; de Castillo, Ibis Soto; Florentin, Sara; Diaz de Bedoya, Fernando Hamuy; Mandler, Raul; de Siervi, Luiza Campanella; Pimentel, Maria Lúcia Vellutini; Alvarenga, Marina Papais; Papais Alvarenga, Marcos; Grzesiuk, Anderson Kuntz; Gama Pereira, Ana Beatriz Calmon; Gomes Neto, Antonio Pereira; Velasquez, Carolina; Soublette, Carlos; Fleitas, Cynthia Veronica; Diniz, Denise Sisteroli; Armas, Elizabeth; Batista, Elizabeth; Hernandez, Freda; Pereira, Fernanda Ferreira Chaves da Costa; Siqueira, Heloise Helena; Cabeça, Hideraldo; Sanchez, Jose; Brooks, Joseph Bruno Bidin; Gonçalves, Marcus Vinicius; Barroso, Maria Cristina Del Negro; Ravelo, Maria Elena; Castillo, Maria Carlota; Ferreira, Maria Lúcia Brito; Rocha, Maria Sheila Guimarães; Parolin, Monica Koncke Fiuza; Molina, Omaira; Marinho, Patricia Beatriz Christino; Christo, Paulo Pereira; Brant de Souza, Renata; Pessanha Neto, Silvio; Camargo, Solange Maria das Graças; Machado, Suzana Costa; Neri, Vanderson Carvalho; Fragoso, Yara Dadalti; Alvarenga, Helcio; Thuler, Luiz Claudio Santos

    2015-01-01

    The idiopathic inflammatory demyelinating disease (IIDD) spectrum has been investigated among different populations, and the results have indicated a low relative frequency of neuromyelitis optica (NMO) among multiple sclerosis (MS) cases in whites (1.2%-1.5%), increasing in Mestizos (8%) and Africans (15.4%-27.5%) living in areas of low MS prevalence. South America (SA) was colonized by Europeans from the Iberian Peninsula, and their miscegenation with natives and Africans slaves resulted in significant racial mixing. The current study analyzed the IIDD spectrum in SA after accounting for the ethnic heterogeneity of its population. A cross-sectional multicenter study was performed. Only individuals followed in 2011 with a confirmed diagnosis of IIDD using new diagnostic criteria were considered eligible. Patients’ demographic, clinical and laboratory data were collected. In all, 1,917 individuals from 22 MS centers were included (73.7% female, 63.0% white, 28.0% African, 7.0% Mestizo, and 0.2% Asian). The main disease categories and their associated frequencies were MS (76.9%), NMO (11.8%), other NMO syndromes (6.5%), CIS (3.5%), ADEM (1.0%), and acute encephalopathy (0.4%). Females predominated in all main categories. The white ethnicity also predominated, except in NMO. Except in ADEM, the disease onset occurred between 20 and 39 years old, early onset in 8.2% of all cases, and late onset occurred in 8.9%. The long-term morbidity after a mean disease time of 9.28±7.7 years was characterized by mild disability in all categories except in NMO, which was scored as moderate. Disease time among those with MS was positively correlated with the expanded disability status scale (EDSS) score (r=0.374; p=<0.001). This correlation was not observed in people with NMO or those with other NMO spectrum disorders (NMOSDs). Among patients with NMO, 83.2% showed a relapsing-remitting course, and 16.8% showed a monophasic course. The NMO-IgG antibody tested using indirect

  1. Central Nervous System Idiopathic Inflammatory Demyelinating Disorders in South Americans: A Descriptive, Multicenter, Cross-Sectional Study.

    PubMed

    Papais-Alvarenga, Regina Maria; Vasconcelos, Claudia Cristina Ferreira; Carra, Adriana; de Castillo, Ibis Soto; Florentin, Sara; Diaz de Bedoya, Fernando Hamuy; Mandler, Raul; de Siervi, Luiza Campanella; Pimentel, Maria Lúcia Vellutini; Alvarenga, Marina Papais; Alvarenga, Marcos Papais; Grzesiuk, Anderson Kuntz; Gama Pereira, Ana Beatriz Calmon; Gomes Neto, Antonio Pereira; Velasquez, Carolina; Soublette, Carlos; Fleitas, Cynthia Veronica; Diniz, Denise Sisteroli; Armas, Elizabeth; Batista, Elizabeth; Hernandez, Freda; Pereira, Fernanda Ferreira Chaves da Costa; Siqueira, Heloise Helena; Cabeça, Hideraldo; Sanchez, Jose; Brooks, Joseph Bruno Bidin; Gonçalves, Marcus Vinicius; Barroso, Maria Cristina Del Negro; Ravelo, Maria Elena; Castillo, Maria Carlota; Ferreira, Maria Lúcia Brito; Rocha, Maria Sheila Guimarães; Parolin, Monica Koncke Fiuza; Molina, Omaira; Marinho, Patricia Beatriz Christino; Christo, Paulo Pereira; Brant de Souza, Renata; Pessanha Neto, Silvio; Camargo, Solange Maria das Graças; Machado, Suzana Costa; Neri, Vanderson Carvalho; Fragoso, Yara Dadalti; Alvarenga, Helcio; Thuler, Luiz Claudio Santos

    2015-01-01

    The idiopathic inflammatory demyelinating disease (IIDD) spectrum has been investigated among different populations, and the results have indicated a low relative frequency of neuromyelitis optica (NMO) among multiple sclerosis (MS) cases in whites (1.2%-1.5%), increasing in Mestizos (8%) and Africans (15.4%-27.5%) living in areas of low MS prevalence. South America (SA) was colonized by Europeans from the Iberian Peninsula, and their miscegenation with natives and Africans slaves resulted in significant racial mixing. The current study analyzed the IIDD spectrum in SA after accounting for the ethnic heterogeneity of its population. A cross-sectional multicenter study was performed. Only individuals followed in 2011 with a confirmed diagnosis of IIDD using new diagnostic criteria were considered eligible. Patients' demographic, clinical and laboratory data were collected. In all, 1,917 individuals from 22 MS centers were included (73.7% female, 63.0% white, 28.0% African, 7.0% Mestizo, and 0.2% Asian). The main disease categories and their associated frequencies were MS (76.9%), NMO (11.8%), other NMO syndromes (6.5%), CIS (3.5%), ADEM (1.0%), and acute encephalopathy (0.4%). Females predominated in all main categories. The white ethnicity also predominated, except in NMO. Except in ADEM, the disease onset occurred between 20 and 39 years old, early onset in 8.2% of all cases, and late onset occurred in 8.9%. The long-term morbidity after a mean disease time of 9.28±7.7 years was characterized by mild disability in all categories except in NMO, which was scored as moderate. Disease time among those with MS was positively correlated with the expanded disability status scale (EDSS) score (r=0.374; p=<0.001). This correlation was not observed in people with NMO or those with other NMO spectrum disorders (NMOSDs). Among patients with NMO, 83.2% showed a relapsing-remitting course, and 16.8% showed a monophasic course. The NMO-IgG antibody tested using indirect

  2. Disease Modifying Therapy in Multiple Sclerosis

    PubMed Central

    Williams, U. E.; Oparah, S. K.; Philip-Ephraim, E. E.

    2014-01-01

    Multiple sclerosis is an autoimmune disease of the central nervous system characterized by inflammatory demyelination and axonal degeneration. It is the commonest cause of permanent disability in young adults. Environmental and genetic factors have been suggested in its etiology. Currently available disease modifying drugs are only effective in controlling inflammation but not prevention of neurodegeneration or accumulation of disability. Search for an effective neuroprotective therapy is at the forefront of multiple sclerosis research. PMID:27355035

  3. Spinal primitive neuroectodermal tumor mimicking as chronic inflammatory demyelination polyneuropathy: a case report and review of literature.

    PubMed

    Chan, Sophelia H S; Tsang, Dickson S F; Wong, Virginia C N; Chan, Godfrey C F

    2015-02-01

    We report a young boy who presented with progressive weakness of lower extremities associated with areflexia and abnormal electrophysiological findings initially suggestive of chronic inflammatory demyelinating polyneuropathy. Initial lumbosacral spinal magnetic resonance imaging (MRI) showed thickened descending spinal nerve roots only. Immunomodulating therapy was given but with limited clinical response. Repeated spine magnetic resonance imaging showed cauda equina and also new spinal cord extramedullary contrast enhancement. The initial extensive investigations including open biopsy did not point to any specific diagnosis. Only through pursuing a repeated biopsy, the diagnosis of the spinal peripheral primitive neuroectodermal tumor was confirmed. This case highlights the diagnostic challenges of the spinal peripheral primitive neuroectodermal tumor that could have an initial chronic inflammatory demyelinating polyneuropathy-like presentation. The literature review confirms that this is a rare condition and cauda equina origin has only been reported in adults and teenagers, and this is the first reported case in a young child.

  4. CNS-specific expression of C3a and C5a exacerbate demyelination severity in the cuprizone model.

    PubMed

    Ingersoll, Sarah A; Martin, Carol B; Barnum, Scott R; Martin, Brian K

    2010-01-01

    Demyelination in the central nervous system (CNS) is known to involve several immune effector mechanisms, including complement proteins. Local production of complement by glial cells in the brain can be both harmful and protective. To investigate the roles of C3a and C5a in demyelination and remyelination pathology we utilized the cuprizone model. Transgenic mice expressing C3a or C5a under the control of the glial fibrillary acidic protein (GFAP) promoter had exacerbated demyelination and slightly delayed remyelination in the corpus callosum compared to WT mice. C3a and C5a transgenic mice had increased cellularity in the corpus callosum due to increase activation and/or migration of microglia. Oligodendrocytes migrated to the corpus callosum in higher numbers during early remyelination events in C3a and C5a transgenic mice, thus enabling these mice to remyelinate as effectively as WT mice by the end of the 10 week study. To determine the effects of C3a and/or C5a on individual glial subsets, we created murine recombinant C3a and C5a proteins. When microglia and mixed glial cultures were stimulated with C3a and/or C5a, we observed an increase in the production of proinflammatory cytokines and chemokines. In contrast, astrocytes had decreased cytokine and chemokine production in the presence of C3a and/or C5a. We also found that the MAPK pathway proteins JNK and ERK1/2 were activated in glia upon stimulation with C3a and C5a. Overall, our findings show that although C3a and C5a production in the brain play a negative role during demyelination, these proteins may aid in remyelination.

  5. Treatment of chronic immune-mediated neuropathies: chronic inflammatory demyelinating polyradiculoneuropathy, multifocal motor neuropathy, and the Lewis-Sumner syndrome.

    PubMed

    Sederholm, Benson H

    2010-09-01

    Current treatment approaches for the management of chronic immune-mediated peripheral neuropathies are reviewed, including chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), multifocal motor neuropathy (MMN), and the Lewis-Sumner syndrome (LSS). A summary of existing evidence for commonly used treatment modalities, such as corticosteroids, intravenous immune globulin (IVIG), and plasma exchange is provided. Evidence for the use of additional immunosuppressant and immunomodulatory agents is also reviewed.

  6. Relationship between Cerebrospinal Fluid Biomarkers for Inflammation, Demyelination and Neurodegeneration in Acute Optic Neuritis

    PubMed Central

    Modvig, Signe; Degn, Matilda; Horwitz, Henrik; Cramer, Stig P.; Larsson, Henrik B. W.; Wanscher, Benedikte; Sellebjerg, Finn; Frederiksen, Jette L.

    2013-01-01

    Background Various inflammatory biomarkers show prognostic potential for multiple sclerosis (MS)-risk after clinically isolated syndromes. However, biomarkers are often examined singly and their interrelation and precise aspects of their associated pathological processes remain unclear. Clarification of these relationships could aid the appropriate implementation of prognostic biomarkers in clinical practice. Objective To investigate the interrelation between biomarkers of inflammation, demyelination and neurodegeneration in acute optic neuritis and to assess their association to measures of MS risk. Material and Methods A prospective study at a tertiary referral centre from June 2011 to December 2012 of 56 patients with optic neuritis as a first demyelinating symptom and 27 healthy volunteers. Lumbar puncture was performed within 28 (median 16) days of onset. CSF levels of CXCL13, matrix metalloproteinase (MMP)-9, CXCL10, CCL-2, osteopontin and chitinase-3-like-1, myelin basic protein (MBP) and neurofilament light-chain (NF-L) were determined. MS-risk outcome measures were dissemination in space (DIS) of white matter lesions on cerebral MRI, CSF oligoclonal bands and elevated IgG-index. Results In the interrelation analysis the biomarkers showed close correlations within two distinct groups: Biomarkers of leukocyte infiltration (CXCL13, MMP-9 and CXCL10) were strongly associated (p<0.0001 for all). Osteopontin and chitinase-3-like-1 were also tightly associated (p<0.0001) and correlated strongly to tissue damage markers (NF-L and MBP). The biomarkers of leukocyte infiltration all associated strongly with MS-risk parameters, whereas CHI3L1 and MBP correlated with MRI DIS, but not with CSF MS-risk parameters and osteopontin and NF-L did not correlate with any MS-risk parameters. Conclusions Our findings suggest two distinct inflammatory processes: one of leukocyte infiltration, represented by CXCL13, CXCL10 and MMP-9, strongly associated with and potentially

  7. Differentiation and quantification of inflammation, demyelination and axon injury or loss in multiple sclerosis.

    PubMed

    Wang, Yong; Sun, Peng; Wang, Qing; Trinkaus, Kathryn; Schmidt, Robert E; Naismith, Robert T; Cross, Anne H; Song, Sheng-Kwei

    2015-05-01

    Axon injury/loss, demyelination and inflammation are the primary pathologies in multiple sclerosis lesions. Despite the prevailing notion that axon/neuron loss is the substrate of clinical progression of multiple sclerosis, the roles that these individual pathological processes play in multiple sclerosis progression remain to be defined. An imaging modality capable to effectively detect, differentiate and individually quantify axon injury/loss, demyelination and inflammation, would not only facilitate the understanding of the pathophysiology underlying multiple sclerosis progression, but also the assessment of treatments at the clinical trial and individual patient levels. In this report, the newly developed diffusion basis spectrum imaging was used to discriminate and quantify the underlying pathological components in multiple sclerosis white matter. Through the multiple-tensor modelling of diffusion weighted magnetic resonance imaging signals, diffusion basis spectrum imaging resolves inflammation-associated cellularity and vasogenic oedema in addition to accounting for partial volume effects resulting from cerebrospinal fluid contamination, and crossing fibres. Quantitative histological analysis of autopsied multiple sclerosis spinal cord specimens supported that diffusion basis spectrum imaging-determined cellularity, axon and myelin injury metrics closely correlated with those pathologies identified and quantified by conventional histological staining. We demonstrated in healthy control subjects that diffusion basis spectrum imaging rectified inaccurate assessments of diffusion properties of white matter tracts by diffusion tensor imaging in the presence of cerebrospinal fluid contamination and/or crossing fibres. In multiple sclerosis patients, we report that diffusion basis spectrum imaging quantitatively characterized the distinct pathologies underlying gadolinium-enhanced lesions, persistent black holes, non-enhanced lesions and non-black hole lesions, a

  8. Mucormycosis in a surgical defect masquerading as osteomyelitis: a case report and review of literature.

    PubMed

    Mengji, Ashwini Kumar; Yaga, Uday Shankar; Gollamudi, Nishanth; Prakash, Bhanu; Rajashekar, Edunuri

    2016-01-01

    Mucormycosis is a rare, highly lethal opportunistic fungal disease affecting immune compromised and diabetic patients. Mucormycosis is considered as the 3(rd) most common invasive mycosis after candidiasis and aspergillosis in debilitating patients. It is caused by the filamentous fungi of the class zygomycetes. The infection usually begins in the nose due to inhalation of fungal spores. This fatal fungal disease needs a prompt and early definitive diagnosis, aggressive surgical therapy and high dose anti-fungal therapy. Here, we present a case report of Mucormycosis in a 64 year elderly diabetic male patient who was previously operated for myiasis and also the extensive review of the literature of the mucormycosis.

  9. [Successful treatment of HIV-associated chronic inflammatory demyelinating polyneuropathy by early initiation of highly active anti-retroviral therapy].

    PubMed

    Kume, Kodai; Ikeda, Kazuyo; Kamada, Masaki; Touge, Tetsuo; Deguchi, Kazushi; Masaki, Tsutomu

    2013-01-01

    A 47-year-old man with HIV infection presented with lower leg dominant dysesthesia, muscle weakness and sensory ataxia of 3 month's duration. Nerve conduction studies (NCS) showed demyelination change in the median and tibial nerves and sensory nerve action potential (SNAP) in the sural nerve was not evoked. Somatosensory evoked potential (SEP) showed the delayed N9 latency. Diagnose of HIV-associated chronic inflammatory demyelinating polyneuropathy (CIDP) was made. Although the CD4 lymphocyte counts were relatively preserved (466/μl), highly active anti-retroviral therapy (HAART) was started according to a new guideline for the use of antiretroviral agents in HIV-1-infected adults and adolescents recommending early initiation of treatment. After six months, HIV1-RNA was not detected and the CD4 lymphocyte counts showed a recovering trend (585/μl). His symptoms had disappeared, except for dysesthesia in the tip of a toe. Repeated NCS demonstrated full recovery from the demyelination and appearance of SNAP in the sural nerve. The improvement of his symptoms and NCS findings has been maintained for two years. Although effectiveness of immunotherapies such as oral prednisone, high-dose immunoglobulins and plasmapheresis have been reported in HIV-associated CIDP, early initiation of HAART may be also important for favorable prognosis in HIV-associated CIDP.

  10. ABLATION OF THE UPR–MEDIATOR CHOP RESTORES MOTOR FUNCTION AND REDUCES DEMYELINATION IN CHARCOT MARIE TOOTH 1B MICE

    PubMed Central

    Pennuto, Maria; Tinelli, Elisa; Malaguti, MariaChiara; Del Carro, Ubaldo; D'Antonio, Maurizio; Ron, David; Quattrini, Angelo; Feltri, M. Laura; Wrabetz, Lawrence

    2008-01-01

    SUMMARY Deletion of serine 63 from P0 glycoprotein (P0S63del) causes Charcot-Marie-Tooth 1B neuropathy in humans, and P0S63del produces a very similar demyelinating neuropathy in transgenic mice. P0S63del is retained in the endoplasmic reticulum and fails to be incorporated into myelin. Here we report that P0S63del is globally misfolded and Schwann cells mount a consequential canonical unfolded protein response (UPR), that includes expression of the transcription factor CHOP, previously associated with apoptosis in ER-stressed cells. UPR activation and CHOP expression respond dynamically to P0S63del levels and are reversible, but are associated with only limited apoptosis of Schwann cells. Nonetheless, Chop ablation in S63del mice completely rescues their motor deficit and reduces active demyelination two-fold. This is the first indication that signaling through the CHOP arm of the UPR provokes demyelination in inherited neuropathy. In addition, S63del mice provide a unique opportunity to explore how cells can dysfunction yet survive in prolonged ER stress—important for neurodegeneration related to misfolded proteins. PMID:18255032

  11. Nivolumab-induced chronic inflammatory demyelinating polyradiculoneuropathy mimicking rapid-onset Guillain-Barré syndrome: a case report.

    PubMed

    Tanaka, Ryota; Maruyama, Hiroshi; Tomidokoro, Yasushi; Yanagiha, Kumi; Hirabayashi, Takumi; Ishii, Akiko; Okune, Mari; Inoue, Sae; Sekine, Ikuo; Tamaoka, Akira; Fujimoto, Manabu

    2016-09-01

    Nivolumab, an anti-programmed death-1-specific monoclonal antibody, has demonstrated a durable response and effect on overall survival and has become one of the standard treatments for patients with advanced melanoma. Reported herein is a case of nivolumab-induced chronic inflammatory demyelinating polyradiculoneuropathy, in which an 85-year-old woman with stage IV melanoma developed grade 1 paresthesia 2 weeks after the initial dose of nivolumab was administered. With continued treatment, the neurological deficiency deteriorated rapidly, mimicking Guillain-Barré syndrome, causing such a dramatic decrease in her activities of daily living that she could no longer function in daily life. Thus, nivolumab treatment was discontinued. A course of intravenous immunoglobulin infusion yielded a dramatic clinical improvement; in particular, improved motor control was observed within a few days. Her initial presentation was suggestive of acute inflammatory demyelinating polyradiculoneuropathy, a subtype of Guillain-Barré syndrome; however, the good response to steroids and exacerbation 8 weeks after the onset were suggestive of chronic inflammatory demyelinating polyradiculoneuropathy induced by nivolumab. This is the first case of Guillain-Barré syndrome-like autoimmune polyradiculoneuropathy induced by programmed death-1/programmed death-ligand 1 inhibitors. Although neurological adverse events related to nivolumab are rare, they can become severe, requiring early diagnosis and intervention. Intravenous immunoglobulin may be considered as an effective initial treatment for patients who develop acute autoimmune nervous system disorders due to nivolumab.

  12. Regulation of Olig2 during astroglial differentiation in the subventricular zone of a cuprizone-induced demyelination mouse model.

    PubMed

    Chen, L P; Li, Z F; Ping, M; Li, R; Liu, J; Xie, X H; Song, X J; Guo, L

    2012-09-27

    The mammalian subventricular zone (SVZ) is the largest germinative zone of the adult brain. Progenitor cells generated from the SVZ play important roles during the remyelination process. To determine the functional role of Olig2 in regulating astroglial differentiation in the mouse SVZ, we used the cuprizone mouse model to investigate demyelination. We found that cuprizone administration significantly enhanced the expression of Olig2 and increased astroglial differentiation in the SVZ, as compared with control. Moreover, cytoplasmic translocation of Olig2 occurred after demyelination. In vitro studies further revealed that supplementation of culture media with growth factors enhanced the oligodendroglial differentiation of oligodendrocyte progenitor cells (OPCs), whereas serum alone promoted astroglial differentiation and cytoplasmic translocation of Olig2. Additionally, the expression levels of bone morphogenetic proteins 2 and 4 (BMP2 and BMP4) and inhibitor of DNA binding 2 and 4 (Id2 and Id4) were greatly elevated during astroglial differentiation. BMP inhibition by noggin suppressed the astroglial differentiation of OPCs. Our results indicate that Olig2 may serve as a key regulator during the directional differentiation of progenitor cells after demyelination. The BMP signaling pathway may contribute to the cytoplasmic translocation and altered expression of Olig2 during the remyelination process. These findings provide a better understanding of the mechanisms involved in remyelination.

  13. Nerve Excitability Properties in Charcot-Marie-Tooth Disease Type 1A

    ERIC Educational Resources Information Center

    Nodera, Hiroyuki; Bostock, Hugh; Kuwabara, Satoshi; Sakamoto, Takashi; Asanuma, Kotaro; Jia-Ying, Sung; Ogawara, Kazue; Hattori, Naoki; Hirayama, Masaaki; Kaji, Ryuji

    2004-01-01

    Charcot-Marie-Tooth disease type 1A (CMT1A) is commonly considered a prototype of a hereditary demyelinating polyneuropathy. Apart from the myelin involvement, there has been little information on axonal membrane properties in this condition. Taking advantage of the uniform nature of the disease process, we undertook the "in vivo" assessment of…

  14. Blood nerve barrier in rat and cellular mechanisms of lead-induced segmental demyelination

    SciTech Connect

    Dyck, P.J.; Windebank, A.J.; Low, P.A.; Baumann, W.J.

    1980-11-01

    Feeding of lead carbonate to rats causes widespread and reproducible segmental de- and remyelination of myelinated fibers (MFs) of peripheral nerve. Such segmental demyelination might be explained by increased permeability of endoneurial capillaries to serum containing protein-bound lead. The perineurium of control and lead nerves was impermeable to fluorescein-labeled bovine albumin (FBA) and to horseradish peroxidase (HRP). Epineurial capillaries in both conditions allowed HRP to pass freely between and, to a lesser extent, through endothelial cells. Contrary to expectation, flooding of the endoneurium with HRP was seen in only 1 of 36 tissue blocks of lead nerves from rats fed 4% lead carbonate for 7 1/2 and 12 weeks. Abundant HRP reaction product was seen in the epineurium in more than half of these tissue blocks. HRP was not generally found in endoneurial fluid, even in lead nerves with marked edema and widespread segmental de- and remyelination. These findings are against a massive breakdown of the blood nerve barrier. These studies suggest that there may be an increased transfer of HRP through endoneurial cells in lead neuropathy.

  15. Inhibition of LINGO-1 promotes functional recovery after experimental spinal cord demyelination.

    PubMed

    Zhang, Yongjie; Zhang, Yi Ping; Pepinsky, Blake; Huang, Guanrong; Shields, Lisa B E; Shields, Christopher B; Mi, Sha

    2015-04-01

    Blocking LINGO-1 has been shown to enhance remyelination in the rat lysolecithin-induced focal spinal cord demyelination model. We used transcranial magnetic motor-evoked potentials (tcMMEPs) to assess the effect of blocking LINGO-1 on recovery of axonal function in a mouse lysolecithin model at 1, 2 and 4weeks after injury. The role of LINGO-1 was assessed using LINGO-1 knockout (KO) mice and in wild-type mice after intraperitoneal administration of anti-LINGO-1 antagonist monoclonal antibody (mAb3B5). Response rates (at 2 and 4weeks) and amplitudes (at 4weeks) were significantly increased in LINGO-1 KO and mAb3B5-treated mice compared with matched controls. The latency of potentials at 4weeks was significantly shorter in mAb3B5-treated mice compared with controls. Lesion areas in LINGO-1 KO and mAb3B5-treated mice were reduced significantly compared with matched controls. The number of remyelinated axons within the lesions was increased and the G-ratios of the axons were decreased in both LINGO-1 KO and mAb3B5-treated mice compared with matched controls. These data provide morphometric and functional evidence of enhancement of remyelination associated with antagonism of LINGO-1.

  16. bFGF Protects Pre-oligodendrocytes from Oxygen/Glucose Deprivation Injury to Ameliorate Demyelination.

    PubMed

    Qu, Xuebin; Guo, Rui; Zhang, Zhenzhong; Ma, Li; Wu, Xiuxiang; Luo, Mengjiao; Dong, Fuxing; Yao, Ruiqin

    2015-10-01

    One of the pathological hallmarks of periventricular white matter injury is the vulnerability of pre-oligodendrocytes (preOLs) to hypoxia-ischemia (HI). There is increasing evidence that basic fibroblast growth factor (bFGF) is an important signaling molecule for neurogenesis and neuroprotection in the central nervous system. However, it is unknown whether bFGF protects preOLs from oxygen/glucose deprivation (OGD) damage in vitro and promotes remyelination in HI-induced rats. In this present study, bFGF exerted a protective effect on myelin by increasing the myelin thickness, the number of myelinated axons, and myelin basic protein expression in the HI-induced demyelinated neonatal rat corpus callosum. In vitro, bFGF ameliorated the impaired mitochondria and cell processes induced by OGD to promote the survival of isolated O4-positive preOLs. Additionally, the expression of fibroblast growth factor receptor 3 (FGFR3) was dramatically up-regulated in the preOLs after bFGF administration in vivo and in vitro. Thus, bFGF-stimulated remyelination in HI-induced rats by protecting the preOLs from hypoxic injury, and the mechanism involved may be mediated by FGFR3.

  17. Acute-onset chronic inflammatory demyelinating polyneuropathy in hantavirus and hepatitis B virus coinfection

    PubMed Central

    Lim, Jong Youb; Lim, Young-Ho; Choi, Eun-Hi

    2016-01-01

    Abstract Introduction: Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired autoimmune disorder with progressive weakness. Acute-onset CIDP resembles Guillain-Barre syndrome (GBS), a rapidly progressive disorder, and follows a chronic course. To our knowledge, no case of acute-onset CIDP in hantavirus and hepatitis B virus (HBV) coinfection has been reported previously. Clinical findings: We report a case of acute-onset CIDP that was initially diagnosed as GBS. Diagnoses: A 44-year-old male logger complained of acute quadriplegia and dyspnea. Mechanical ventilation was initiated. He was an HBV carrier with mild elevation of hepatic enzyme, and positive for hantavirus antibody. He was diagnosed with GBS and immunoglobulin therapy was administered. Interventions: After 8 months, quadriplegia and hypesthesia recurred. Immunoglobulin therapy at this time had no effect, but steroid therapy had some effect. Outcomes: A diagnosis of CIDP was made. After 2 months, severe extremity pain and dyspnea developed again, and steroid pulse therapy was initiated. Conclusion: Besides GBS, acute-onset CIDP can occur with hantavirus and HBV coinfection. Patients with this coinfection in whom GBS has been initially diagnosed should be followed up for a long time, because of the possibility of relapse or deterioration, and acute-onset CIDP should always be considered. PMID:27930572

  18. Chronic inflammatory demyelinating polyneuropathy: decreased claudin-5 and relocated ZO-1

    PubMed Central

    Kanda, T; Numata, Y; Mizusawa, H

    2004-01-01

    Objectives: To clarify the dynamics of molecules composing the blood–nerve barrier (BNB) in inflammatory neuropathies. Methods: The expression of four tight junction (TJ) proteins—claudin-1, claudin-5, occludin, and ZO-1—was analysed immunohistochemically in sural nerve biopsy specimens obtained from patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Results: Claudin-1 was detected only in perineurial cells, whereas claudin-5 was present in endothelial cells, irrespective of vessel location or size. Occludin and ZO-1 were found in perineurial cells, in addition to some epineurial and endoneurial endothelial cells. In CIDP, percentages of endoneurial small vessels immunoreactive for claudin-5 were significantly decreased, as were ZO-1 immunoreactive endoneurial small vessels, with staining localised to interfaces between cells. Claudin-1 and occludin immunoreactivity did not differ appreciably between the neuropathies examined. Conclusions: The downregulation of claudin-5 and altered localisation of ZO-1 seen in CIDP specimens may indicate that BNB derangement occurs in inflammatory neuropathies. Further investigation of TJ molecules may suggest new treatments based on properties of the BNB. PMID:15090575

  19. Shortened internodal length of dermal myelinated nerve fibres in Charcot–Marie-Tooth disease type 1A

    PubMed Central

    Saporta, Mario A.; Katona, Istvan; Lewis, Richard A.; Masse, Stacey; Shy, Michael E.

    2009-01-01

    Charcot–Marie-Tooth disease type 1A is the most common inherited neuropathy and is caused by duplication of chromosome 17p11.2 containing the peripheral myelin protein-22 gene. This disease is characterized by uniform slowing of conduction velocities and secondary axonal loss, which are in contrast with non-uniform slowing of conduction velocities in acquired demyelinating disorders, such as chronic inflammatory demyelinating polyradiculoneuropathy. Mechanisms responsible for the slowed conduction velocities and axonal loss in Charcot–Marie-Tooth disease type 1A are poorly understood, in part because of the difficulty in obtaining nerve samples from patients, due to the invasive nature of nerve biopsies. We have utilized glabrous skin biopsies, a minimally invasive procedure, to evaluate these issues systematically in patients with Charcot–Marie-Tooth disease type 1A (n = 32), chronic inflammatory demyelinating polyradiculoneuropathy (n = 4) and healthy controls (n = 12). Morphology and molecular architecture of dermal myelinated nerve fibres were examined using immunohistochemistry and electron microscopy. Internodal length was uniformly shortened in patients with Charcot–Marie-Tooth disease type 1A, compared with those in normal controls (P < 0.0001). Segmental demyelination was absent in the Charcot–Marie-Tooth disease type 1A group, but identifiable in all patients with chronic inflammatory demyelinating polyradiculoneuropathy. Axonal loss was measurable using the density of Meissner corpuscles and associated with an accumulation of intra-axonal mitochondria. Our study demonstrates that skin biopsy can reveal pathological and molecular architectural changes that distinguish inherited from acquired demyelinating neuropathies. Uniformly shortened internodal length in Charcot–Marie-Tooth disease type 1A suggests a potential developmental defect of internodal lengthening. Intra-axonal accumulation of mitochondria provides new insights into the

  20. Primary cutaneous anaplastic large cell lymphoma masquerading as large pyogenic granuloma

    PubMed Central

    Bains, Anupama; Vedant, Deepak; Shanker, Vinay; Tegta, G. R.

    2016-01-01

    Primary cutaneous anaplastic large cell lymphoma (pcALCL) forms 9% of the cutaneous T-cell lymphomas. It usually presents as solitary reddish brown ulcerating nodule or indurated plaque. Sometimes, it mimics other dermatological diseases such as eczema, pyoderma gangrenosum, pyogenic granuloma, morphea, and squamous cell carcinoma. Our case presented with large pyogenic granuloma like lesion with regional lymphadenopathy. Since pcALCL is rare, one can misdiagnose such cases and therefore high index of suspicion is necessary. PMID:27990392

  1. Rare Presentation of Genitourinary Tuberculosis Masquerading as Renal Cell Carcinoma: A Histopathological Surprise

    PubMed Central

    Kumar, Santosh; Shankaregowda, Sriharsha Ajjoor; Choudhary, Gautam Ram; Singla, Karun

    2014-01-01

    Genitourinary tuberculosis (GUTB) is a rare extrapulmonary manifestation of tuberculosis (TB). Various forms of presentation are described and in most cases the disease results in calcification, atrophy, or necrosis of the renal parenchyma. The kidney is not generally palpable except in cases of hydronephrosis due to an upper ureteric stricture. We present a case of GUTB presenting as inflammatory pseudotumor. This case was initially diagnosed as renal malignancy and managed accordingly. Histopathology confirmed the diagnosis of pseudotumoral renal TB. PMID:24991477

  2. Takayasu arteritis masquerading as stable angina in a 29-year-old man.

    PubMed

    Wang, Lei; Ma, Teng; Zhao, Yun-Tao

    2017-04-01

    Takayasu arteritis is a form of vasculitis that involves the aorta, its major branches, and the pulmonary arteries. Coronary artery involvement is not uncommon, and most frequently includes the ostia and proximal segments. Early diagnosis of Takayasu arteritis is difficult since it is a rare disease and is accompanied by various nonspecific clinical symptoms. However, recent advances in imaging modalities-including magnetic resonance angiography, computed tomography (CT), sonography, and fluoro-deoxyglucose positron emission tomography (FDG-PET)/CT Isobe (2013) [2]-have facilitated earlier and more accurate diagnoses of this condition. Here we report a case in which imaging revealed stenosis in the ostia of the coronary artery.

  3. Amiodarone Induced Hyponatremia Masquerading as Syndrome of Inappropriate Antidiuretic Hormone Secretion by Anaplastic Carcinoma of Prostate

    PubMed Central

    Dutta, Pinaki; Kumar, Santosh; Kakkar, Nandita; Bhansali, Anil; Rotondo, Fabio; Kovacs, Kalman

    2014-01-01

    Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is one of the most common causes of hyponatremia. The usual causes are malignancies, central nervous system, pulmonary disorders, and drugs. Amiodarone is a broad spectrum antiarrhythmic agent widely used in the management of arrhythmias. The different side effects include thyroid dysfunction, visual disturbances, pulmonary infiltrates, ataxia, cardiac conduction abnormalities, drug interactions, corneal microdeposits, skin rashes, and gastrointestinal disturbances. SIADH is a rare but lethal side effect of amiodarone. We describe a 62-year-old male who was suffering from advanced prostatic malignancy, taking amiodarone for underlying heart disease. He developed SIADH which was initially thought to be paraneoplastic in etiology, but later histopathology refuted that. This case emphasizes the importance of detailed drug history and the role of immunohistochemistry in establishing the diagnosis and management of hyponatremia due to SIADH. PMID:24818037

  4. Langerhans cell histiocytosis masquerading as acute appendicitis: Case report and review

    PubMed Central

    Karimzada, Mohammad M; Matthews, Michele N; French, Samuel W; DeUgarte, Daniel; Kim, Dennis Y

    2017-01-01

    Langerhans cell histiocytosis (LCH) is a rare syndrome characterized by unifocal, multifocal unisystem, or disseminated/multi-system disease that commonly involves the bone, skin, lymph nodes, pituitary, or sometimes lung (almost exclusively in smokers) causing a variety of symptoms from rashes and bone lesions to diabetes insipidus or pulmonary infiltrates. We present a previously unreported case of gastrointestinal LCH as well as a novel characteristic lesion affecting the colon of a young woman who presented with signs and symptoms mimicking acute on chronic appendicitis. Immunohistochemical analysis of appendectomy specimen and nodular specimens on colonoscopy demonstrated S-100, CD1a, and langerin reactivity. The patient underwent systemic chemotherapy with cytarabine and demonstrated excellent response to therapy. PMID:28360976

  5. Paraspinal and Extensive Epidural Abscess: The Great Masqueraders of Abdominal Pain

    PubMed Central

    Chu, Andrew; Aung, Thu Thu; Shankar, Uday

    2015-01-01

    Paraspinal and epidural abscesses are rare conditions often diagnosed later in the disease process that can have significant morbidity and mortality. Predisposing risk factors include diabetes, human immunodeficiency virus, intravenous drug abuse, and previous history of spinal surgery or injection. They can threaten the spinal cord by compressive effect, leading to sensory motor deficits and ultimately paralysis and death. Diagnosis may be a challenge due to the delayed presentation of nonspecific back pain or radicular pain such as chest pain or abdominal pain. We present a rare case on a patient with periumbilical pain, constipation, and urinary retention who was ultimately diagnosed with a paraspinal abscess extending into the epidural space from T1 to S2. He underwent decompressive laminectomy with incision and drainage of the abscesses. The patient made an excellent recovery postoperatively, and repeat magnetic resonance imaging at six weeks showed resolution of the abscess. PMID:26770847

  6. Bolster material granuloma masquerading as recurrent renal cell carcinoma following partial nephrectomy

    PubMed Central

    Singh, Abhishek; Jai, Shrikant; Ganpule, Sanika; Ganpule, Arvind

    2016-01-01

    Nephron sparing surgery has seen a phenomenal rise in its application over the past few decades. The use of Surgicel and gel foam for closure of defect created after partial nephrectomy has become a routine practice at many centers. In this case report, we describe radiological artifact secondary to a surgical bolster mimicking a residual disease or an early recurrence in the kidney. This case highlights two facts; first, reapproximation of the renal tissue is best done without the use of Surgicel bolsters. Second, bolsteroma should always be kept in mind as a differential diagnosis in a case where computed tomography (CT) imaging is showing early recurrence. If the surgeon is sure about the surgical margins being negative and the CT image shows a bolsteroma, the patient should be observed and a repeat scan should be done at 3–6 months, which would show regression or disappearance of the lesion proving it to be an artifact rather than malignant lesion. PMID:27857461

  7. The appendix: a spectrum of benign and malignant disease.

    PubMed

    Lord, Christopher; Broadhurst, Jack; Sleight, Simon; McGee, Shaun; Wills, Mark

    2017-02-02

    This article discusses the radiological appearances and subsequent management of a diverse spectrum of benign and malignant appendiceal pathologies, including those masquerading as acute appendicitis.

  8. The Farnsworth-Munsell 100 hue test in the first episode of demyelinating optic neuritis.

    PubMed

    Ménage, M J; Papakostopoulos, D; Dean Hart, J C; Papakostopoulos, S; Gogolitsyn, Y

    1993-02-01

    The Farnsworth-Munsell 100 hue test (F-M 100) was used to examine 30 patients with their first episode of unilateral demyelinating optic neuritis (DON) at presentation, after 6 weeks and after 6 months. Twelve patients satisfactorily completed the test with the affected eye at presentation. This number had increased to 23 by 6 weeks and to 27 by 6 months. No patient with a visual acuity of LogMAR 0.86 (Snellen equivalent approx 6/43) or worse, could complete the test. The mean total error score of affected eyes showed significant improvement at each subsequent examination but was always worse than the non-affected eyes. There was a significant correlation between total error scores and visual acuities of affected eyes at presentation and after 6 months. Fourteen patients recovered a visual acuity of LogMAR 0.0 (Snellen equivalent 6/6) or better but the total error scores of the affected eyes were significantly worse than the non-affected eyes (p = 0.017), indicating that defective colour vision is an indicator of a previous episode of DON despite the recovery of normal visual acuity. DON is reported to produce a red-green (Type II) axis of colour defect but individual F-M 100 polar diagrams were usually generally abnormal and did not show any predominance of recognisable axis of colour defect at any examination. Group averaging of the F-M 100 data from such a well-defined group of patients with acute DON revealed a significant bipolar abnormality in the tritan (blue-yellow) axis at presentation which was not demonstrated at the subsequent examinations or at any examination of the non-affected eyes.

  9. [NMDA receptor encephalitis in the course of recurrent CNS demyelinating disorders: a case report].

    PubMed

    Yamamoto, Masanari; Kokubun, Norito; Watanabe, Yuka; Okabe, Ryuta; Nakamura, Toshiki; Hirata, Koichi

    2013-01-01

    We present the case of a 31-year-old woman who developed N-methyl-d-aspartate (NMDA) receptor encephalitis during the course of relapsing and remitting multiple brain lesions. The patient developed a tingling sensation in the left upper and lower extremities, and was first admitted to our hospital at age 27. She was tentatively diagnosed with multiple sclerosis on the basis of multiple lesions with Gd-enhancement in the brainstem, and 2 separate clinical relapses by age 28. At age 31, she developed a headache and pyrexia, followed by confusion and abnormal behavior. Her symptoms acutely progressed to stupor, and subsequently, she developed oral dyskinesia and athetosis-like involuntary movement of the left arm. The stupor state continued over 2 months. However, she had completely recovered by 3 months after the onset of psychiatric symptoms. Her serum and CSF samples tested positive for anti-NMDA receptor antibodies, and she was diagnosed with NMDA receptor encephalitis. Her serum was negative for anti-AQP4 antibody, but showed weak positivity for antinuclear antibody. Between ages 32 and 34, she experienced 2 clinical relapses, including right-hand clumsiness, confusion, aphasia, and dysphagia. FLAIR images showed a high-intensity area in the brain stem, thalamus, and subcortical white matter. No tumors were found throughout the course. A clinical entity of NMDA receptor encephalitis can include various neurologic disorders, such as the development of recurrent demyelinating brain lesions. Further investigation is required to clarify the pathophysiological role of anti-NMDA receptor antibody in our patient.

  10. Steroids for chronic inflammatory demyelinating polyradiculoneuropathy: evidence base and clinical practice.

    PubMed

    Press, R; Hiew, F L; Rajabally, Y A

    2016-04-01

    Evidence-based therapies for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) consist of corticosteroids, intravenous immunglobulins (IVIg), and plasma exchange. Steroids represent the oldest treatment used historically. In countries where readily available and affordable, IVIg tends to be favored as first-line treatment. The reason for this preference, despite substantially higher costs, is the perception that IVIg is more efficacious and safer than corticosteroids. However, the unselected use of IVIg as a first-line treatment option in all cases of CIDP raises issues of cost-effectiveness in the long-term. Furthermore, serious although rare, particularly thromboembolic side effects may result from their use. Recent data from randomized trials suggest pulsed corticosteroids to have a higher potential in achieving therapy-free remission or longer remission-free periods compared with IVIg, as well as relatively low rates of serious side effects when given as pulsed intravenous infusions during short periods of time. These specific advantages suggest that pulsed steroids could in many cases be used, as the first, rather than second choice of treatment when initiating immunomodulation in CIDP, primarily in hopes of achieving a remission after the short-term use. This article reviews the evidence base for the use of corticosteroids in its various forms in CIDP and factors that may influence clinicians' choice between IVIg and pulsed steroid treatment. The issue of efficacy, relapse rate and time, and side effect profile are analyzed, and some aspects from the authors' experience are discussed in relation to the possibility of using the steroid option as first-line therapy in a large proportion of patients with CIDP.

  11. MRI study of the cuprizone-induced mouse model of multiple sclerosis: demyelination is not found after co-treatment with polyprenols (long-chain isoprenoid alcohols)

    NASA Astrophysics Data System (ADS)

    Khodanovich, M.; Glazacheva, V.; Pan, E.; Akulov, A.; Krutenkova, E.; Trusov, V.; Yarnykh, V.

    2016-02-01

    Multiple sclerosis is a neurological disorder with poorly understood pathogenic mechanisms and a lack of effective therapies. Therefore, the search for new MS treatments remains very important. This study was performed on a commonly used cuprizone animal model of multiple sclerosis. It evaluated the effect of a plant-derived substance called Ropren® (containing approximately 95% polyprenols or long-chain isoprenoid alcohols) on cuprizone- induced demyelination. The study was performed on 27 eight-week old male CD-1 mice. To induce demyelination mice were fed 0.5% cuprizone in the standard diet for 10 weeks. Ropren® was administered in one daily intraperitoneal injection (12mg/kg), beginning on the 6th week of the experiment. On the 11th week, the corpus callosum in the brain was evaluated in all animals using magnetic resonance imaging with an 11.7 T animal scanner using T2- weighted sequence. Cuprizone treatment successfully induced the model of demyelination with a significant decrease in the size of the corpus callosum compared with the control group (p<0.01). Mice treated with both cuprizone and Ropren® did not exhibit demyelination in the corpus callosum (p<0.01). This shows the positive effect of polyprenols on cuprizone-induced demyelination in mice.

  12. Nodular sclerosing classical Hodgkin lymphoma masquerading as acute suppurative-necrotizing lymphadenitis.

    PubMed

    Florentine, Barbara D; Cohen, Alen N

    2014-03-01

    The diagnosis of nodular sclerosing classical Hodgkin lymphoma (NSCHL) by fine-needle aspiration (FNA) biopsy has historically been a diagnostic challenge due to the usual paucicellularity of the specimen. This case report, and other previously published reports, suggests that there is another facet to the potentially challenging diagnosis of this particular variant of Hodgkin lymphoma (HL): the presence of suppurative-necrotizing changes mimicking an infectious etiology. The patient presented here underwent FNA biopsy of an acutely enlarged supraclavicular lymph node and cytologic smears showed marked acute inflammation in a background of necrosis. A diagnosis of infectious suppurative lymphadenitis was made at that time. After a negative infectious work-up with infectious disease consultation, an excisional biopsy was performed and the patient was definitively diagnosed with NSCHL. The presence of neoplastic Hodgkin and Reed-Sternberg cells in the purulent exudate was minimal and only appropriately identified after retrospective review. This particular subtype of classical HL represents a potential pitfall in FNA biopsy cytology. Consequently, the cytopathologist and surgeon should always consider this entity in the differential diagnosis of a suppurative, lymphadenitis-like aspirate, and pursue repeat FNA or an excisional biopsy if there is any clinical index of suspicion.

  13. Idiopath=ic Granulomatous Lobular Mastitis Masquerading as a Breast Tumor: A Case Report

    PubMed Central

    Raman R, Thulasi; Manimaran, D

    2016-01-01

    Introduction Idiopathic granulomatous lobular mastitis (IGLM) is an inflammatory disease of the breast with an obscure etiology. It occurs mainly in women of reproductive age, and the lesion mimics carcinoma of the breast both clinically and radiologically Case Presentation We present the case of a 29-year-old female who visited our hospital in Kancheepuram, Tamil Nadu, with a 4 × 3 cm lump in the upper outer quadrant of her left breast. The clinical and radiological findings were indicative of a malignant lesion; however, fine-needle aspiration cytology (FNAC) revealed features of granulomatous mastitis, and the subsequent histology of the excised lump confirmed the diagnosis of IGLM. Conclusions IGLM should be considered as one of the differential diagnoses when granulomas are encountered in breast FNAC and biopsy. A definitive diagnosis of IGLM can be made by identifying its characteristic histomorphology and ruling out other causes for granulomatous inflammation. An exact diagnosis is essential since the treatment for different granulomatous conditions of the breast varies. PMID:27437133

  14. Unrelenting Ocular Pain as a Masquerading Symptom of Occult Choroidal Metastasis

    PubMed Central

    Deaner, Jordan D.; Pointdujour-Lim, Renelle; Say, Emil Anthony T.; Shields, Carol L.

    2017-01-01

    Purpose To report a case of chronic eye pain as a presenting feature of choroidal metastasis from lung cancer. Methods We report the case of a 58-year-old Caucasian woman with stage IV lung adenocarcinoma presenting with an 8-month history of left eye pain and blurred vision. Results The patient had previously consulted 14 ophthalmologists with varying diagnoses including posterior scleritis and trigeminal neuralgia. Visual acuity at presentation was 20/20 in the right eye and 20/80 in the left eye. Examination of the right eye was normal, while the left eye showed ill-defined flat yellow discoloration of the choroid with overlying shifting subretinal fluid. Ultrasonography demonstrated a dense choroidal thickening measuring 2.6 mm in size and showing subretinal fluid. Enhanced depth imaging optical coherence tomography revealed choroidal thickening with a ‘lumpy bumpy’ surface topography consistent with a metastatic choroidal tumor presumably from the patient's lung adenocarcinoma. Fine needle aspiration biopsy followed by treatment was recommended, but the patient declined and later succumbed to metastatic disease. Conclusion We present a case of chronic eye pain associated with diffuse choroidal thickening from metastatic lung adenocarcinoma that was previously unrecognized and misdiagnosed. This case emphasizes the importance of recognizing pain as a presenting symptom of choroidal metastasis. PMID:28275605

  15. Choroidal abnormalities and masquerade syndromes confounding the diagnosis of laser-induced eye injuries

    NASA Astrophysics Data System (ADS)

    Hacker, Henry D.; Zwick, Harry; Brown, Jeremiah, Jr.; Dicks, Ronald; Cheramie, Rachel; Stuck, Bruce E.

    2005-04-01

    The diagnosis of a laser-induced eye injury occurring in occupational or military environments is often complicated by confounding symptoms, the possibility of pre-existing pathology, and/or a lack of visual deficits that can be clearly associated with a specific incident. Two recent cases are described that illustrate the importance of a thorough differential diagnosis when coexisting retinal pathologies are present with potentially different (e.g. laser or disease) etiologies. Indocyanine green angiography (ICG) and ocular coherence tomography (OCT) used in combination with standard ophthalmic imaging can provide helpful insights as to the etiology of these lesions. Vascular choroidal abnormalities such as hemangiomas or occult histoplasmosis infection can produce findings that can mimic the leakage that may be evident from neovascular membranes associated with laser injury. Further evaluation with OCT and conventional fluorescein angiography (FA) is helpful to look for the classic signature of retinal disruption and retinal pigment layer changes that are often present in association with laser injury. Furthermore, a careful situational assessment of a potential laser exposure is important to confirm the diagnosis of laser-induced eye injury.

  16. Neuromuscular Diseases Associated with HIV-1 Infection

    PubMed Central

    Robinson-Papp, Jessica; Simpson, David M.

    2010-01-01

    Neuromuscular disorders are common in HIV, occurring at all stages of disease and affecting all parts of the peripheral nervous system. These disorders have diverse etiologies including HIV itself, immune suppression and dysregulation, co-morbid illnesses and infections, and side effects of medications. In this article, we review the following HIV-associated conditions: distal symmetric polyneuropathy, inflammatory demyelinating polyneuropathy, mononeuropathy, mononeuropathy multiplex, autonomic neuropathy, progressive polyradiculopathy due to cytomegalovirus, herpes zoster, myopathy and other rarer disorders. PMID:19771594

  17. Effect of vitamin E on ectonucleotidase activities in synaptosomes and platelets and parameters of oxidative stress in rats experimentally demyelinated.

    PubMed

    Spanevello, Roselia; Mazzanti, Cinthia M; Schmatz, Roberta; Bagatini, Margarete; Stefanello, Naiara; Correa, Maisa; Kaizer, Rosilene; Maldonado, Paula; Mazzanti, Alexandre; Graça, Dominguita L; Martins, Tessie B; Danesi, Cristiane; Morsch, Vera M; Schetinger, Maria Rosa C

    2009-08-28

    NTPDase and 5'-nucleotidase activities in synaptosomes and platelets and oxidative stress parameters, such as TBARS levels, non-protein thiols and catalase activity were analyzed in rats submitted to demyelination by ethidium bromide (EB) and treated with vitamin E. The following groups were studied: I control (saline); II (canola oil); III (vitamin E); IV (EB) and V (EB and vitamin E). 2mg/kg of vitamin E were injected intraperitoneally in animals from groups III and V for seven days. After this time, the animals were submitted to euthanasia and samples were collected for biochemical assays. The results showed that NTPDase and 5'-nucleotidase activities were significantly increased in synaptosomes and platelets of rats from group IV when compared with the groups I, II, III and V (p<0.05). When demyelinated rats were treated with vitamin E (group V), NTPDase activity in synaptosomes and platelets was reduced to control level, while 5'-nucleotidase activity was significantly increased in relation to the control group (p<0.05). TBARS levels and non-protein thiols were significantly increased in group IV (p<0.05), while catalase activity was significantly decreased in this group when compared with the control group (p<0.05). No differences in TBARS levels, non-protein thiols and catalase activity were observed in groups I, II, III and V. These findings demonstrate that ectonucleotidase activities in synaptosomes and platelets and some parameters of oxidative stress were altered after a demyelinating event on the nervous system and that treatment with vitamin E modulated adenine nucleotide hydrolysis and altered oxidative stress parameters in this experimental condition.

  18. Bacillary Angiomatosis Masquerading as Kaposi’s Sarcoma in East Africa

    PubMed Central

    Forrestel, A. K.; Naujokas, A.; Martin, J. N.; Maurer, T. A.; McCalmont, T. H.; Laker-Opwonya, M. O.; Mulyowa, G.; Busakhala, N.; Amerson, Erin H.

    2015-01-01

    Background Bacillary angiomatosis (BA) is a rare manifestation of infection caused by Bartonella species, which leads to vasoproliferative lesions of skin and other organs. Bacillary angiomatosis affects individuals with advanced HIV disease or other immunocompromised individuals. In sub-Saharan Africa, despite the high prevalence of HIV infection and documentation of the causative Bartonella species in humans, mammalian hosts, and arthropod vectors, BA has only rarely been described. Methods Three adult patients from Uganda and Kenya with deep purple dome-shaped papules or nodules of the skin underwent punch biopsies for histopathologic diagnosis. The biopsies of all 3 patients were sent to a local pathologist as well as to a dermatopathologist at the University of California, San Francisco. Results All 3 patients were clinically suspected to have Kaposi’s sarcoma (KS), and local pathologists had interpreted the lesions as KS in 2 of the cases and nonspecific inflammation in the third. Histologic examination by dermatopathologists in the United States revealed nodular dermal proliferations of irregular capillaries lined by spindled to epithelioid endothelial cells. The surrounding stroma contained a mixed inflammatory infiltrate with lymphocytes, eosinophils, and neutrophils. Extracellular deposits of pale amphophilic granular material were noted in the surrounding stroma. A Warthin-Starry stain highlighted clumps of bacilli, confirming the diagnosis of BA. Conclusions These 3 cases, to our knowledge, are the first reports of BA in East Africa in the biomedical literature. Each had been originally incorrectly diagnosed as KS. We speculate BA is underdiagnosed and underreported in resource-poor regions, such as sub- Saharan Africa, that have high endemic rates of HIV infection. PMID:24718378

  19. [Devic's disease in an adolescent girl with juvenile dermatomyositis].

    PubMed

    Fraga, Melissa Mariti; Oliveira, Enedina Maria Lobato de; Len, Claudio Arnaldo; Campos, Maria Fernanda; Terreri, Maria Teresa

    2015-01-28

    Devic's disease, also known as neuromyelitis optica, is an autoimmune inflammatory demyelinating disorder of the central nervous system that mainly affects the optic nerve and spinal cord. Recently, Devic's disease was demonstrated to be a channelopathy due to the presence of antibodies against the water channel aquaporin-4 in the blood-brain barrier. There have been reports of Devic's disease in infancy, but there are few reported associations of Devic's disease with other diseases. The association of Devic's disease with dermatomyositis has not yet been described in the literature. The aim of this paper is to describe the first case of Devic's disease in an adolescent with juvenile dermatomyositis.

  20. IL-2 Suppression of IL-12p70 by a Recombinant HSV-1 Expressing IL-2 Induces T-Cell Auto-Reactivity and CNS Demyelination

    PubMed Central

    Zandian, Mandana; Mott, Kevin R.; Allen, Sariah J.; Chen, Shuang; Arditi, Moshe; Ghiasi, Homayon

    2011-01-01

    To evaluate the role of cellular infiltrates in CNS demyelination in immunocompetent mice, we have used a model of multiple sclerosis (MS) in which different strains of mice are infected with a recombinant HSV-1 expressing IL-2. Histologic examination of the mice infected with HSV-IL-2 demonstrates that natural killer cells, dendritic cells, B cells, and CD25 (IL-2rα) do not play any role in the HSV-IL-2-induced demyelination. T cell depletion, T cell knockout and T cell adoptive transfer experiments suggest that both CD8+ and CD4+ T cells contribute to HSV-IL-2-induced CNS demyelination with CD8+ T cells being the primary inducers. In the adoptive transfer studies, all of the transferred T cells irrespective of their CD25 status at the time of transfer were positive for expression of FoxP3 and depletion of FoxP3 blocked CNS demyelination by HSV-IL-2. The expression levels of IL-12p35 relative to IL-12p40 differed in BM-derived macrophages infected with HSV-IL-2 from those infected with wild-type HSV-1. HSV-IL-2-induced demyelination was blocked by injecting HSV-IL-2-infected mice with IL-12p70 DNA. This study demonstrates that suppression of the IL-12p70 function of macrophages by IL-2 causes T cells to become auto-aggressive. Interruption of this immunoregulatory axis results in demyelination of the optic nerve, the spinal cord and the brain by autoreactive T cells in the HSV-IL-2 mouse model of MS. PMID:21364747

  1. An autopsy case of classical Pelizaeus-Merzbacher's disease.

    PubMed

    Konishi, Y; Kamoshita, S

    1975-01-01

    A girl aged 8 years and 10 months at death had shown signs of a slowly progressive neurological disease with onset in early infancy. The main clinical features were nystagmus, spastic paraplegia, amd mental deterioration. Pathological examination of the brain showed severe demyelination with perivascular preservation of mylein islands, presenting a tigroid pattern. The patient is the second case of classical Pelizaeus-Merzbacher's disease in Japan proven by autopsy.

  2. Cat Scratch Disease: Expanded Spectrum

    PubMed Central

    Aziz, Hassan A.; Plesec, Thomas P.; Sabella, Camille; Udayasankar, Unni K.; Singh, Arun D.

    2016-01-01

    Background To expand the spectrum of ophthalmic manifestations in cat scratch disease. Methods Case report. Results A 7-year-old male was referred for evaluation of his left optic disc after failing vision screening test at school. His visual acuity was 20/20 OD and light perception OS. Fundus examination showed a left optic disc lesion associated with an exudative retinal detachment and vitreous seeding. Ultrasonography revealed a 7 × 7.5 × 3.8 mm lesion with a possible 6.3 mm of retrolaminar extension into the substance of the optic nerve. Brain MRI did not show evidence of optic nerve involvement but revealed a 6-mm nodule of the pineal gland suggestive of a pineoblastoma. Enucleation was performed and histopathology revealed a suppurative granulomatous inflammation suggestive of Bartonella infection. Upon further questioning, the patient had recent exposure to kittens with areas of cat scratches along both of his arms. He was subsequently referred to and treated with a 2-week course of trimethoprim-sulfamethoxazole and rifampin by the pediatric infectious disease specialist. Repeat brain MRI showed interval total resolution of enlarged pineal gland. Conclusion: Optic nerve granulomas are a rare presentation of cat scratch disease and could potentially masquerade as retinoblastoma. PMID:27843905

  3. Sildenafil (Viagra) Protective Effects on Neuroinflammation: The Role of iNOS/NO System in an Inflammatory Demyelination Model

    PubMed Central

    Raposo, Catarina; Nunes, Ana Karolina de Santana; Luna, Rayana Leal de Almeida; Araújo, Shyrlene Meiry da Rocha; da Cruz-Höfling, Maria Alice; Peixoto, Christina Alves

    2013-01-01

    We recently demonstrated that sildenafil reduces the expression of cytokines, COX-2, and GFAP in a demyelinating model induced in wild-type (WT) mice. Herein, the understandings of the neuroprotective effect of sildenafil and the mediation of iNOS/NO system on inflammatory demyelination induced by cuprizone were investigated. The cerebella of iNOS−/− mice were examined after four weeks of treatment with cuprizone alone or combined with sildenafil. Cuprizone increased GFAP, Iba-1, TNF-α, COX-2, IL-1β, and IFN-γ expression, decreased expression of glutathione S-transferase pi (GSTpi), and damaged myelin in iNOS−/− mice. Sildenafil reduced Iba-1, IFN-γ, and IL-1β levels but had no effect on the expression of GFAP, TNF-α, and COX-2 compared to the cuprizone group. Sildenafil elevated GSTpi levels and improved the myelin structure/ultrastructure. iNOS−/− mice suffered from severe inflammation following treatment with cuprizone, while WT mice had milder inflammation, as found in the previous study. It is possible that inflammatory regulation through iNOS-feedback is absent in iNOS−/− mice, making them more susceptible to inflammation. Sildenafil has at least a partial anti-inflammatory effect through iNOS inhibition, as its effect on iNOS−/− mice was limited. Further studies are required to explain the underlying mechanism of the sildenafil effects. PMID:23970812

  4. Retinitis Pigmentosa and Bilateral Idiopathic Demyelinating Optic Neuritis in a 6-Year-Old Boy with OFD1 Gene Mutation

    PubMed Central

    Wang, Xun; Zheng, Cong; Liu, Wen

    2017-01-01

    To identify the cause of a sudden binocular vision decrease in patients with retinitis pigmentosa and bilateral idiopathic demyelinating optic neuritis is difficult, but early diagnosis and treatment significantly improve the prognosis. Here, we report a 6-year-old boy with a progressive binocular vision decrease in 38 days. The patient had a history of night blindness, a mottled retina without pigmentation, extinguished electroretinographic response, tritanopia, and an absent ellipsoid zone outside the macula fovea by optical coherence tomography in both eyes. His condition was diagnosed as retinitis pigmentosa (RP) with idiopathic demyelinating optic neuritis (IDON). After corticosteroid therapy, visual acuity recovered to OD: 0.5 and OS: 0.4. Genetic analysis revealed a G985S variant in the oral-facial-digital syndrome 1 gene. Ophthalmologists should pay attention to the existence of other complications in patients with RP who suffer a sudden decrease in vision. A gene survey can help clarify this diagnosis. To our knowledge, this is the first report of a patient with RP and ON, as well as genetic testing results. Nevertheless, the pathogenicity of the variant needs further confirmation. PMID:28191358

  5. Sudden blindness in a child with Crohn’s disease

    PubMed Central

    Barabino, Arrigo Vittorio; Gandullia, Paolo; Calvi, Angela; Vignola, Silvia; Arrigo, Serena; Marco, Riccardo De

    2011-01-01

    Inflammatory bowel disease (IBD) is often associated with extraintestinal manifestations (EIMs) such as optic neuritis (ON), although this has been described in only a few adult patients so far, all of whom were affected with Crohn’s disease (CD). Furthermore, ON and demyelinating diseases have been demonstrated to be more frequent in IBD patients than in control populations. In our current case report, we describe a child with active CD who developed sudden blindness due to bilateral ON that was not related to any known cause, and that promptly responded to a high dose of steroids. Investigations and a clinical follow-up have so far ruled out the development of demyelinating diseases in this patient. To our knowledge, this is the first report of ON in a pediatric patient with CD. Possible explanations for this case include an episodic EIM of an active bowel disease, an associated autoimmune disorder such as a recurrent isolated ON, the first manifestation of multiple sclerosis, or another demyelinating disease that could appear in a later follow-up. PMID:22090792

  6. Krabbe Disease

    MedlinePlus

    ... Your doctor may order one or more imaging tests that can detect the loss of myelin (demyelination) in affected regions of the brain. These may include: Magnetic resonance imaging (MRI), a technology that uses radio waves and a magnetic field ...

  7. Effects of Reducing Suppressors of Cytokine Signaling-3 (SOCS3) Expression on Dendritic Outgrowth and Demyelination after Spinal Cord Injury

    PubMed Central

    Park, Keun Woo; Lin, Ching-Yi; Li, Kevin; Lee, Yu-Shang

    2015-01-01

    Suppressors of cytokine signaling-3 (SOCS3) is associated with limitations of nerve growth capacity after injury to the central nervous system. Although genetic manipulations of SOCS3 can enhance axonal regeneration after optic injury, the role of SOCS3 in dendritic outgrowth after spinal cord injury (SCI) is still unclear. The present study investigated the endogenous expression of SOCS3 and its role in regulating neurite outgrowth in vitro. Interleukin-6 (IL-6) induces SOCS3 expression at the mRNA and protein levels in neuroscreen-1 (NS-1) cells. In parallel to SOCS3 expression, IL-6 induced tyrosine phosphorylation of signal transducer and activator of transcription 3 (STAT3) in NS-1 cells. Lentiviral delivery of short hairpin RNA (shSOCS3) (Lenti-shSOCS3) to decrease SOCS3 expression into NS-1 cells enhanced IL-6-induced tyrosine phosphorylation of STAT3 (P-STAT3 Tyr705) and promoted neurite outgrowth. In addition, we determined if reduction of SOCS3 expression by microinjection of Lenti-shSOCS3 into spinal cord enhances dendrite outgrowth in spinal cord neurons after SCI. Knocking down of SOCS3 in spinal cord neurons with Lenti-shSOCS3 increased complete SCI-induced P-STAT3 Tyr705. Immunohistochemical analysis showed that complete SCI induced a significant reduction of microtubule association protein 2-positive (MAP-2+) dendrites in the gray and white matter at 1 and 4 weeks after injury. The SCI-induced reduction of MAP-2+ dendrites was inhibited by infection with Lenti-shSOCS3 in areas both rostral and caudal to the lesion at 1 and 4 weeks after complete SCI. Furthermore, shSOCS3 treatment enhanced up-regulation of growth associated protein-43 (GAP-43) expression, which co-localized with MAP-2+ dendrites in white matter and with MAP-2+ cell bodies in gray matter, indicating Lenti-shSOCS3 may induce dendritic regeneration after SCI. Moreover, we demonstrated that Lenti-shSOCS3 decreased SCI-induced demyelination in white matter of spinal cord both rostral and

  8. Osmotic demyelination syndrome complicating diabetes with anti-glutamic acid decarboxylase antibodies and Graves' disease: A case report.

    PubMed

    Tajitsu, Machiko; Yamada, Tsutomu; Cao, Xia; Fukui, Ayako; Nagai, Junko; Yambe, Yuko; Murase, Takashi; Okada, Hisashi

    2016-01-01

    ODS associated with hyperglycemia is rare, with few reports.Immune responses have been recently reported as a mechanism of ODS onset. In the present case, an autoimmune predisposition may have contributed to ODS pathogenesis.

  9. N-cadherin promotes recruitment and migration of neural progenitor cells from the SVZ neural stem cell niche into demyelinated lesions.

    PubMed

    Klingener, Michael; Chavali, Manideep; Singh, Jagdeep; McMillan, Nadia; Coomes, Alexandra; Dempsey, Peter J; Chen, Emily I; Aguirre, Adan

    2014-07-16

    Discrete cellular microenvironments regulate stem cell pools and their development, as well as function in maintaining tissue homeostasis. Although the signaling elements modulating neural progenitor cells (NPCs) of the adult subventricular zone (SVZ) niche are fairly well understood, the pathways activated following injury and the resulting outcomes, are less clear. In the present study, we used mouse models of demyelination and proteomics analysis to identify molecular cues present in the adult SVZ niche during injury, and analyzed their role on NPCs in the context of promoting myelin repair. Proteomic analysis of SVZ tissue from mice with experimental demyelination identified several proteins that are known to play roles in NPC proliferation, adhesion, and migration. Among the proteins found to be upregulated were members of the N-cadherin signaling pathway. During the onset of demyelination in the subcortical white matter (SCWM), activation of epidermal growth factor receptor (EGFR) signaling in SVZ NPCs stimulates the interaction between N-cadherin and ADAM10. Upon cleavage and activation of N-cadherin signaling by ADAM10, NPCs undergo cytoskeletal rearrangement and polarization, leading to enhanced migration out of the SVZ into demyelinated lesions of the SCWM. Genetically disrupting either EGFR signaling or ADAM10 inhibits this pathway, preventing N-cadherin regulated NPC polarization and migration. Additionally, in vivo experiments using N-cadherin gain- and loss-of-function approaches demonstrated that N-cadherin enhances the recruitment of SVZ NPCs into demyelinated lesions. Our data revealed that EGFR-dependent N-cadherin signaling physically initiated by ADAM10 cleavage is the response of the SVZ niche to promote repair of the injured brain.

  10. Elevated protein carbonylation, and misfolding in sciatic nerve from db/db and Sod1(-/-) mice: plausible link between oxidative stress and demyelination.

    PubMed

    Hamilton, Ryan T; Bhattacharya, Arunabh; Walsh, Michael E; Shi, Yun; Wei, Rochelle; Zhang, Yiqiang; Rodriguez, Karl A; Buffenstein, Rochelle; Chaudhuri, Asish R; Van Remmen, Holly

    2013-01-01

    Diabetic peripheral polyneuropathy is associated with decrements in motor/sensory neuron myelination, nerve conduction and muscle function; however, the mechanisms of reduced myelination in diabetes are poorly understood. Chronic elevation of oxidative stress may be one of the potential determinants for demyelination as lipids and proteins are important structural constituents of myelin and highly susceptible to oxidation. The goal of the current study was to determine whether there is a link between protein oxidation/misfolding and demyelination. We chose two distinct models to test our hypothesis: 1) the leptin receptor deficient mouse (dbdb) model of diabetic polyneuropathy and 2) superoxide dismutase 1 knockout (Sod1(-/-) ) mouse model of in vivo oxidative stress. Both experimental models displayed a significant decrement in nerve conduction, increase in tail distal motor latency as well as reduced myelin thickness and fiber/axon diameter. Further biochemical studies demonstrated that oxidative stress is likely to be a potential key player in the demyelination process as both models exhibited significant elevation in protein carbonylation and alterations in protein conformation. Since peripheral myelin protein 22 (PMP22) is a key component of myelin sheath and has been found mutated and aggregated in several peripheral neuropathies, we predicted that an increase in carbonylation and aggregation of PMP22 may be associated with demyelination in dbdb mice. Indeed, PMP22 was found to be carbonylated and aggregated in sciatic nerves of dbdb mice. Sequence-driven hydropathy plot analysis and in vitro oxidation-induced aggregation of purified PMP22 protein supported the premise for oxidation-dependent aggregation of PMP22 in dbdb mice. Collectively, these data strongly suggest for the first time that oxidation-mediated protein misfolding and aggregation of key myelin proteins may be linked to demyelination and reduced nerve conduction in peripheral neuropathies.

  11. Longitudinal in vivo coherent anti-Stokes Raman scattering imaging of demyelination and remyelination in injured spinal cord

    NASA Astrophysics Data System (ADS)

    Shi, Yunzhou; Zhang, Delong; Huff, Terry B.; Wang, Xiaofei; Shi, Riyi; Xu, Xiao-Ming; Cheng, Ji-Xin

    2011-10-01

    In vivo imaging of white matter is important for the mechanistic understanding of demyelination and evaluation of remyelination therapies. Although white matter can be visualized by a strong coherent anti-Stokes Raman scattering (CARS) signal from axonal myelin, in vivo repetitive CARS imaging of the spinal cord remains a challenge due to complexities induced by the laminectomy surgery. We present a careful experimental design that enabled longitudinal CARS imaging of de- and remyelination at single axon level in live rats. In vivo CARS imaging of secretory phospholipase A2 induced myelin vesiculation, macrophage uptake of myelin debris, and spontaneous remyelination by Schwann cells are sequentially monitored over a 3 week period. Longitudinal visualization of de- and remyelination at a single axon level provides a novel platform for rational design of therapies aimed at promoting myelin plasticity and repair.

  12. Dynamic Visual Tests to Identify and Quantify Visual Damage and Repair Following Demyelination in Optic Neuritis Patients

    PubMed Central

    Raz, Noa; Hallak, Michal; Ben-Hur, Tamir; Levin, Netta

    2014-01-01

    In order to follow optic neuritis patients and evaluate the effectiveness of their treatment, a handy, accurate and quantifiable tool is required to assess changes in myelination at the central nervous system (CNS). However, standard measurements, including routine visual tests and MRI scans, are not sensitive enough for this purpose. We present two visual tests addressing dynamic monocular and binocular functions which may closely associate with the extent of myelination along visual pathways. These include Object From Motion (OFM) extraction and Time-constrained stereo protocols. In the OFM test, an array of dots compose an object, by moving the dots within the image rightward while moving the dots outside the image leftward or vice versa. The dot pattern generates a camouflaged object that cannot be detected when the dots are stationary or moving as a whole. Importantly, object recognition is critically dependent on motion perception. In the Time-constrained Stereo protocol, spatially disparate images are presented for a limited length of time, challenging binocular 3-dimensional integration in time. Both tests are appropriate for clinical usage and provide a simple, yet powerful, way to identify and quantify processes of demyelination and remyelination along visual pathways. These protocols may be efficient to diagnose and follow optic neuritis and multiple sclerosis patients. In the diagnostic process, these protocols may reveal visual deficits that cannot be identified via current standard visual measurements. Moreover, these protocols sensitively identify the basis of the currently unexplained continued visual complaints of patients following recovery of visual acuity. In the longitudinal follow up course, the protocols can be used as a sensitive marker of demyelinating and remyelinating processes along time. These protocols may therefore be used to evaluate the efficacy of current and evolving therapeutic strategies, targeting myelination of the CNS. PMID

  13. Utility of CSF Cytokine/Chemokines as Markers of Active Intrathecal Inflammation: Comparison of Demyelinating, Anti-NMDAR and Enteroviral Encephalitis

    PubMed Central

    Kothur, Kavitha; Wienholt, Louise; Mohammad, Shekeeb S.; Tantsis, Esther M.; Pillai, Sekhar; Britton, Philip N.; Jones, Cheryl A.; Angiti, Rajeshwar R.; Barnes, Elizabeth H.; Schlub, Timothy; Bandodkar, Sushil; Brilot, Fabienne; Dale, Russell C.

    2016-01-01

    Background Despite the discovery of CSF and serum diagnostic autoantibodies in autoimmune encephalitis, there are still very limited CSF biomarkers for diagnostic and monitoring purposes in children with inflammatory or autoimmune brain disease. The cause of encephalitis is unknown in up to a third of encephalitis cohorts, and it is important to differentiate infective from autoimmune encephalitis given the therapeutic implications. Aim To study CSF cytokines and chemokines as diagnostic biomarkers of active neuroinflammation, and assess their role in differentiating demyelinating, autoimmune, and viral encephalitis. Methods We measured and compared 32 cytokine/chemokines using multiplex immunoassay and APRIL and BAFF using ELISA in CSF collected prior to commencing treatment from paediatric patients with confirmed acute disseminated encephalomyelitis (ADEM, n = 16), anti-NMDAR encephalitis (anti-NMDAR E, n = 11), and enteroviral encephalitis (EVE, n = 16). We generated normative data using CSF from 20 non-inflammatory neurological controls. The sensitivity of CSF cytokine/chemokines to diagnose encephalitis cases was calculated using 95th centile of control values as cut off. We correlated CSF cytokine/chemokines with disease severity and follow up outcome based on modified Rankin scale. One-way hierarchical correlational cluster analysis of molecules was performed in different encephalitis and outcome groups. Results In descending order, CSF TNF-α, IL-10, IFN-α, IL-6, CXCL13 and CXCL10 had the best sensitivity (>79.1%) when all encephalitis patients were included. The combination of IL-6 and IFN-α was most predictive of inflammation on multiple logistic regression with area under the ROC curve 0.99 (CI 0.97–1.00). There were no differences in CSF cytokine concentrations between EVE and anti-NMDAR E, whereas ADEM showed more pronounced elevation of Th17 related (IL-17, IL-21) and Th2 (IL-4, CCL17) related cytokine/chemokines. Unlike EVE, heat map analysis

  14. Adrenoleukodystrophy: a forgotten diagnosis in children with primary Addison's disease

    PubMed Central

    Nascimento, Marta; Rodrigues, Nádia; Espada, Filipa; Fonseca, Marcelo

    2012-01-01

    The X linked adrenoleukodystrophy (X-ALD) is a peroxisomal disease caused by defects of the ABCD1 gene on chromosome Xq28 leading to accumulation of very long chain fatty acids (VLCFA), progressive demyelination and adrenal insufficiency. An 8-year-old boy was referred to our paediatric endocrinology clinic due to fatigue and hyperpigmentation with onset at 2-years old. Blood tests revealed mineralocorticoid insufficiency. Serum adrenocorticotropic hormone and cortisol concentrations were compatible with adrenal insufficiency. Adrenal antibodies were negative. The elevated plasmatic concentration of VLCFA and the genotype analysis with sequencing of ABCD1 gene established the diagnosis of X-ALD. Brain MRI showed demyelination of white matter in the peritrigonal regions. Steroid replacement was started with good response. He initiated restriction of VLCFA by reducing the intake of fatty foods. The authors highlight the importance of suspecting of X-ALD in the aetiology of primary adrenal insufficiency as the first sign of the disease. PMID:22914231

  15. Autoimmune neuropathies associated to rheumatic diseases.

    PubMed

    Martinez, Alberto R M; Faber, Ingrid; Nucci, Anamarli; Appenzeller, Simone; França, Marcondes C

    2017-04-01

    Systemic manifestations are frequent in autoimmune rheumatic diseases and include peripheral nervous system damage. Neuron cell body, axons and myelin sheath may all be affected in this context. This involvement results in severe and sometimes disabling symptoms. Sensory, motor and autonomic features may be present in different patterns that emerge as peculiar clinical pictures. Prompt recognition of these neuropathies is pivotal to guide treatment and reduce the risks of long term disability. In this review, we aim to describe the main immune-mediated neuropathies associated to rheumatic diseases: sensory neuronopathies, multiple mononeuropathies and chronic inflammatory demyelinating polyradiculoneuropathy, with an emphasis on clinical features and therapeutic options.

  16. A Case of Primary Mammary Analog Secretory Carcinoma (MASC) of the Thyroid Masquerading as Papillary Thyroid Carcinoma: Potentially More than a One Off.

    PubMed

    Reynolds, S; Shaheen, M; Olson, G; Barry, M; Wu, J; Bocklage, T

    2016-09-01

    We present the second reported mammary analog secretory carcinoma (MASC) apparently arising in the thyroid and propose a potential close relationship to ETV6-NTRK3 fusion papillary thyroid carcinoma. The patient, a 36 year old woman, presented with a neck mass of 1 year's duration. Imaging studies showed a tumor involving most of the thyroid with enlarged regional lymph nodes. FNA biopsy yielded a diagnosis of "papillary thyroid carcinoma". Resection revealed a 4.5 cm infiltrative tumor. Final diagnosis was "papillary thyroid carcinoma (PTC) consistent with diffuse sclerosing variant" with positive lymph nodes (2+/4) and margins. Histologic features included mixed microcystic, solid, follicular and papillary architecture, prominent nucleoli, abundant nuclear grooves and rare nuclear pseudo-inclusions. Despite radioactive iodine, radiotherapy and multiagent chemotherapy, the patient progressed over 6 years with local recurrence and additional lymph node involvement finally developing widespread distant metastases. Prompted by the breast carcinoma-like histopathology of a metastasis, immunohistochemical staining was performed and revealed strong expression of GATA3 and mammaglobin with no reactivity for thyroglobulin or TTF-1. The original tumor was then tested and showed the same immunoprofile. RT-PCR confirmed the presence of an ETV6-NTRK3 fusion consistent with a diagnosis of MASC. Our patient's clinical, imaging and morphologic features remarkably mimicked papillary thyroid carcinoma. At the molecular level, the ETV6-NTRK3 fusion in this patient involved exons reported in the rare "papillary thyroid carcinoma" with this translocation. Given the immunophenotype of this case, it is possible that at least some ETV6-NTRK3 fusion positive PTC are actually MASC masquerading as papillary thyroid carcinoma.

  17. Three clinical cases of the DiGeorge syndrome manifested with the biliary system disease.

    PubMed

    Tabutsadze, T; Pachkoria, Kh; Atuashvili, G

    2007-11-01

    DiGeorge syndrome is a rare congenital disease that affects the baby's immune system. Its symptoms vary greatly between individuals but commonly include a history of recurrent infection, heart defects, and characteristic facial features. Few cases of DiGeorge syndrome have been reported in adults. The article describes rare (three cases of DiGeorge syndrome) in adults (18, 32 and 34 years old patients) in Georgia (Caucasus). In clinical practice DiGeorge syndrome may proceed under the course of gastroenterologic, endocrine, nervous and surgical symptoms. 3 cases of DiGeorge syndrome are reported in the article. The authors describe DiGeroge syndrome as a multidisciplinary disorder; it is masqueraded by acute surgical diseases; with sharp immunodeficiency and endocrine, cardiologic and neurologic semiotics.

  18. Grafted Human iPS Cell-Derived Oligodendrocyte Precursor Cells Contribute to Robust Remyelination of Demyelinated Axons after Spinal Cord Injury

    PubMed Central

    Kawabata, Soya; Takano, Morito; Numasawa-Kuroiwa, Yuko; Itakura, Go; Kobayashi, Yoshiomi; Nishiyama, Yuichiro; Sugai, Keiko; Nishimura, Soraya; Iwai, Hiroki; Isoda, Miho; Shibata, Shinsuke; Kohyama, Jun; Iwanami, Akio; Toyama, Yoshiaki; Matsumoto, Morio; Nakamura, Masaya; Okano, Hideyuki

    2015-01-01

    Summary Murine- and human-induced pluripotent stem cell-derived neural stem/progenitor cells (iPSC-NS/PCs) promote functional recovery following transplantation into the injured spinal cord in rodents and primates. Although remyelination of spared demyelinated axons is a critical mechanism in the regeneration of the injured spinal cord, human iPSC-NS/PCs predominantly differentiate into neurons both in vitro and in vivo. We therefore took advantage of our recently developed protocol to obtain human-induced pluripotent stem cell-derived oligodendrocyte precursor cell-enriched neural stem/progenitor cells and report the benefits of transplanting these cells in a spinal cord injury (SCI) model. We describe how this approach contributes to the robust remyelination of demyelinated axons and facilitates functional recovery after SCI. PMID:26724902

  19. Guillain-Barré syndrome during adalimumab therapy for Crohn´s disease: coincidence or consequence?

    PubMed

    Cançado, Guilherme Grossi Lopes; Vilela, Eduardo Garcia

    2017-04-01

    We report the case of a 64-year-old patient diagnosed with extensive ileal Crohn´s disease who developed Guillain-Barré syndrome after starting biological therapy with adalimumab. Neurologic involvement associated with inflammatory bowel diseases is recognized as an extra-intestinal manifestation. After the breakthrough of antitumor necrosis factor alpha (anti-TNF-α) agents, an increasing number of cases of acute inflammatory demyelinating polyneuropathies have been reported; however, only one case has been described in a patient with Crohn´s disease. Although a causal relationship between Guillain-Barré syndrome and TNF-α antagonist therapy cannot be proven, this report emphasizes the need to monitor for neurologic signs and symptoms in patients with inflammatory bowel diseases, with or without biological therapy, to avoid severe and irreversible complications associated with demyelinating diseases.

  20. Role of Th17 cells in the pathogenesis of CNS inflammatory demyelination

    PubMed Central

    Rostami, Abdolmohamad; Ciric, Bogoljub

    2013-01-01

    Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS). The etiology of MS is not well understood, but it is believed that myelin-specific CD4+ T cells play a central role in initiating and orchestrating CNS inflammation. In this scenario, CD4+ T cells, activated in the periphery, infiltrate the CNS, where, by secreting cytokines and chemokines, they start an inflammatory cascade. Given the central role of CD4+ T cells in CNS autoimmunity, they have been studied extensively, principally by using experimental autoimmune encephalomyelitis (EAE), an animal model of MS. In the late 1980s, CD4+ T cells, based on their cytokine production, were divided into two helper lineages, Th1 and Th2 cells. It was postulated that Th1 cells, which produce IFN-γ, mediate inflammation of the CNS in MS/EAE, while Th2 cells, which produce IL-4, have a beneficial effect in disease, because of their antagonistic effect on Th1 cells. The Th1/Th2 paradigm remained the prevailing view of MS/EAE pathogenesis until 2005, when a new lineage, Th17, was discovered. In a relatively short period of time it became apparent that Th17 cells, named after their hallmark cytokine, IL-17A, play a crucial role in many inflammatory diseases, including EAE, and likely in MS as well. The Th17 paradigm developed rapidly, initiating the debate whether Th1 cells contribute to EAE/MS pathogenesis at all, or if they might even have a protective role due to their antagonistic effects on Th17 cells. Numerous findings support the view that Th17 cells play an essential role in autoimmune CNS inflammation, perhaps mainly in the initial phases of disease. Th1 cells likely contribute to pathogenesis, with their role possibly more pronounced later in disease. Hence, the current view on the role of Th cells in MS/EAE pathogenesis can be called the Th17/Th1 paradigm. It is certain that Th17 cells will continue to be the focus of intense investigation aimed at elucidating the pathogenesis of

  1. Role of Th17 cells in the pathogenesis of CNS inflammatory demyelination.

    PubMed

    Rostami, Abdolmohamad; Ciric, Bogoljub

    2013-10-15

    Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS). The etiology of MS is not well understood, but it is believed that myelin-specific CD4(+) T cells play a central role in initiating and orchestrating CNS inflammation. In this scenario, CD4(+) T cells, activated in the periphery, infiltrate the CNS, where, by secreting cytokines and chemokines, they start an inflammatory cascade. Given the central role of CD4(+) T cells in CNS autoimmunity, they have been studied extensively, principally by using experimental autoimmune encephalomyelitis (EAE), an animal model of MS. In the late 1980s, CD4(+) T cells, based on their cytokine production, were divided into two helper lineages, Th1 and Th2 cells. It was postulated that Th1 cells, which produce IFN-γ, mediate inflammation of the CNS in MS/EAE, while Th2 cells, which produce IL-4, have a beneficial effect in disease, because of their antagonistic effect on Th1 cells. The Th1/Th2 paradigm remained the prevailing view of MS/EAE pathogenesis until 2005, when a new lineage, Th17, was discovered. In a relatively short period of time it became apparent that Th17 cells, named after their hallmark cytokine, IL-17A, play a crucial role in many inflammatory diseases, including EAE, and likely in MS as well. The Th17 paradigm developed rapidly, initiating the debate of whether Th1 cells contribute to EAE/MS pathogenesis at all, or if they might even have a protective role due to their antagonistic effects on Th17 cells. Numerous findings support the view that Th17 cells play an essential role in autoimmune CNS inflammation, perhaps mainly in the initial phases of disease. Th1 cells likely contribute to pathogenesis, with their role possibly more pronounced later in disease. Hence, the current view on the role of Th cells in MS/EAE pathogenesis can be called the Th17/Th1 paradigm. It is certain that Th17 cells will continue to be the focus of intense investigation aimed at elucidating the

  2. Clinical and electrophysiological characteristics of neuropathy associated with Tangier disease.

    PubMed

    Zyss, Julie; Béhin, Anthony; Couvert, Philippe; Bouhour, Françoise; Sassolas, Agnès; Kolev, Ivan; Denys, Violaine; Vial, Christophe; Lacour, A; Carrié, Alain; Stojkovic, Tanya

    2012-06-01

    Tangier disease (TD) (OMIM#205400) is a rare autosomal recessive disorder resulting from mutations in the ABCA1 gene, leading to decreased levels of plasma high-density lipoproteins (HDL). Peripheral neuropathy is a common finding in this disease, and may present as relapsing/remitting mono/polyneuropathies or as syringomyelia-like neuropathy. We retrospectively analyzed four patients, and report here their clinical, biological, electrophysiological, imaging, and genetic findings. Three patients had a typical pseudosyringomyelic neuropathy including facial diplegia, but asymmetrical onset was observed in one patient who had first been misdiagnosed with Lewis-Sumner syndrome. Electrophysiological pattern was heterogeneous, showing both signs of demyelination and axonal degeneration. Truncating mutations of the ABCA1 gene, including two previously undescribed mutations, were constantly found. Atypical symptom onset and demyelinating features on electrophysiological examination can be misleading in case of pseudosyringomyelic neuropathy. These reports illustrate two different neurological phenotypes in TD, namely the pseudosyringomyelic type and the Lewis-Sumner-like type, and advocate for a systematic assessment of lipid profile including HDL cholesterol in demyelinating neuropathies.

  3. Subcutaneous vs intravenous administration of immunoglobulin in chronic inflammatory demyelinating polyneuropathy: an Italian cost-minimization analysis.

    PubMed

    Lazzaro, Carlo; Lopiano, Leonardo; Cocito, Dario

    2014-07-01

    Prior researches have suggested that home-based subcutaneous immunoglobulin (SCIG) is equally effective and can be less expensive than hospital-based intravenous immunoglobulin (IVIG) in treating chronic inflammatory demyelinating polyneuropathy (CIDP) patients. This economic evaluation aims at comparing costs of SCIG vs IVIG for CIDP patients in Italy. A 1-year model-based cost-minimization analysis basically populated via neurologists' opinion was undertaken from a societal perspective. Health care resources included immunoglobulin; drugs for premedication and complications (rash, headache, and hypertension) management; time of various health care professionals; pump for SCIG self-administration; infusion disposables. Non-health care resources encompassed transport and parking; losses of working and leisure time for patients and caregivers. Unit or yearly costs for resources valuation were mainly obtained from published sources. Costs were expressed in Euro () 2013. An extensive one-way sensitivity analysis (OWSA) and a scenario SA tested the robustness of the base case findings. Overall costs per patient amount to 49,534.75 (SCIG) and 50,895.73 (IVIG); saving in favour of SCIG reaches 1360.98. For both SCIG and IVIG, the cost driver was immunoglobulin (94.06 vs 86.06 % of the overall costs, respectively). Sensitivity analyses confirmed the consistency of the baseline results. SCIG may be a cost-saving therapy for Italian CIDP patients.

  4. Localized Langerhans cell histiocytosis masquerading as Brodie's abscess in a 2-year-old child: a case report

    PubMed Central

    Chang, Wei-Fang; Hsu, Yi-Chih; Wu, Yi-Der; Kuo, Chun-Lang; Huang, Guo-Shu

    2016-01-01

    Langerhans cell histiocytosis (LCH), formerly known as histiocytosis X, refers to a spectrum of diseases characterized by idiopathic proliferation of histiocytes that produce either focal (localized LCH) or systemic manifestations (Hand-Schüller-Christian disease and Letterer-Siwe disease). Localized LCH accounts for approximately 60-70 % of all LCH cases. Osseous involvement is the most common manifestation and typically involves the flat bones, along with lesions of the skull, pelvis, and ribs. Localized LCH in bone shows a wide spectrum of clinical manifestations and radiologic features that may mimic those of infections as well as benign and malignant tumors. The diagnostic imaging findings of localized LCH are also diverse and challenging. The penumbra sign is a common and characteristic magnetic resonance imaging (MRI) feature of Brodie's abscess, but is rarely seen in localized LCH. In this report, we describe a case of localized LCH misdiagnosed as Brodie's abscess in a 2-year-old child based on clinical symptoms, laboratory findings, and pre-diagnostic MRI findings (penumbra sign). Therefore, the penumbra sign is not sufficient to clearly establish the diagnosis of Brodie's abscess, and the differential diagnosis of localized LCH should be considered when a child with an osteolytic lesion presents with a penumbra sign. PMID:27065773

  5. Catastrophic NAD+ Depletion in Activated T Lymphocytes through Nampt Inhibition Reduces Demyelination and Disability in EAE

    PubMed Central

    Ferrando, Tiziana; Poggi, Alessandro; Garuti, Anna; D'Urso, Agustina; Selmo, Martina; Benvenuto, Federica; Cea, Michele; Zoppoli, Gabriele; Moran, Eva; Soncini, Debora; Ballestrero, Alberto; Sordat, Bernard; Patrone, Franco; Mostoslavsky, Raul; Uccelli, Antonio; Nencioni, Alessio

    2009-01-01

    Nicotinamide phosphoribosyltransferase (Nampt) inhibitors such as FK866 are potent inhibitors of NAD+ synthesis that show promise for the treatment of different forms of cancer. Based on Nampt upregulation in activated T lymphocytes and on preliminary reports of lymphopenia in FK866 treated patients, we have investigated FK866 for its capacity to interfere with T lymphocyte function and survival. Intracellular pyridine nucleotides, ATP, mitochondrial function, viability, proliferation, activation markers and cytokine secretion were assessed in resting and in activated human T lymphocytes. In addition, we used experimental autoimmune encephalomyelitis (EAE) as a model of T-cell mediated autoimmune disease to assess FK866 efficacy in vivo. We show that activated, but not resting, T lymphocytes undergo massive NAD+ depletion upon FK866-mediated Nampt inhibition. As a consequence, impaired proliferation, reduced IFN-γ and TNF-α production, and finally autophagic cell demise result. We demonstrate that upregulation of the NAD+-degrading enzyme poly-(ADP-ribose)-polymerase (PARP) by activated T cells enhances their susceptibility to NAD+ depletion. In addition, we relate defective IFN-γ and TNF-α production in response to FK866 to impaired Sirt6 activity. Finally, we show that FK866 strikingly reduces the neurological damage and the clinical manifestations of EAE. In conclusion, Nampt inhibitors (and possibly Sirt6 inhibitors) could be used to modulate T cell-mediated immune responses and thereby be beneficial in immune-mediated disorders. PMID:19936064

  6. Adult-onset demyelinating neuropathy associated with FBLN5 gene mutation.

    PubMed

    Cheng, Si; Lv, He; Zhang, Wei; Wang, Zhaoxia; Shi, Xin; Liang, Wei; Yuan, Yun

    2017-03-23

    Rare forms of autosomal-dominant Charcot-Marie-Tooth disease (AD-CMT) may be associated with mutations in Fibulin-5 (FBLN5) as AD-CMT is genetically heterogeneous. Here, we report the first pathological study of an Asian family. The proband was a 46-year-old man with slowly progressive distal numbness and weakness for 12 years. He had a history of diabetes mellitus for 12 years. His mother was 81 years old and had mild polyneuropathy. His 16-year-old daughter was asymptomatic. The nerve conduction velocities (NCVs) and compound muscular action potential (CMAP) amplitudes were moderately to severely reduced in the proband, and moderately reduced in his daughter and mother. A sensory response could not be elicited in the proband and was moderately to severely decreased in the daughter and mother. Nerve ultrasound indicated a general enlargement of the peripheral nerves in the proband, daughter, and mother. A sural nerve biopsy from the proband demonstrated a pronounced depletion of myelinated fibers, thin myelinated fibers, and onion-bulb formations. A reported heterozygous mutation of c.1117C>T in FBLN5 was identified in the proband, mother, and daughter. These findings confirm a novel subtype of AD-CMT 1 due to a mutation in the FBLN5 gene.
.

  7. Vimentin-positive astrocytes in canine distemper: a target for canine distemper virus especially in chronic demyelinating lesions?

    PubMed

    Seehusen, Frauke; Orlando, Enzo A; Wewetzer, Konstantin; Baumgärtner, Wolfgang

    2007-12-01

    In canine distemper demyelinating leukoencephalitis (DL), caused by canine distemper virus (CDV), astrocytes represent the main virus target. In these cells, glial fibrillary acidic protein (GFAP) is the main intermediate filament, whereas vimentin occurs early in the astrocytic lineage and is replaced gradually by GFAP. To further characterize the role of astrocytic infection in dogs with DL, an animal model for multiple sclerosis, formalin-fixed paraffin-embedded cerebella were investigated immunohistochemically and by immunofluorescence. The expression and morphological alterations of these intermediate filaments were also determined by immunofluorescence studies of CDV-infected canine mixed brain cell cultures. In acute distemper lesions, the astrocytic response was mainly composed of GFAP- and CDV-positive cells. In contrast, vimentin-positive astrocyte-like cells were present in advanced lesions