Intrathecal IgM Synthesis Research Articles

Optic Neuritis and Acute Transverse Myelitis after Chikungunya virus infection

Background: Since 2015, an outbreak of the Chikungunya virus (CHIKV), was identified in north and northeastern Brazil and Caribbean. The infection has demonstrated itself to be benign and self-limited in the vast majority of cases; however, complications, including injuries to the central and peripheral nervous systems, have been reported. Complete Acute Transverse Myelitis (ATM) associated with Optic Neuritis (ON) after this virus infection has never been reported in the literature. Methods & Materials: Medical record and clinical interview. Results: Case report: 63-year-old white woman, presented after acute fever, headache, and arthralgia, urinary retention associated with progressive paraparesis, evolving with paraplegia in a few days. Simultaneously presented reduction of visual acuity, sudden installation, associated with bilateral diplopia. The beginning of neurological symptoms surfaced about of 30 days after the beginning of fever. Confirmed the serological diagnosis of CHIKV (IgM/ELISA). Spinal cord MRI showed multiple lesions in cervical and thoracic areas, with gadolinium uptake. Assessment of visual acuity was reduced in both eyes, with bilateral scotomas. Cerebrospinal fluid analysis revealed normal patterns of protein and glucose, but lymphocytic pleocytosis. Bacterial (Gram and Ziehl Neelsen methods), fungal (Cryptococcus) and viral (herpes simplex, cytomegalovirus, varicella-zoster, HTLV, dengue, zika and chikungunya) analyses were negative; intrathecal synthesis of IgG, IgM and oligoclonal bands presented with normal values. Blood test results were normal throughout the clinical course. She began treatment with methylprednisolone (1 g/daily) for 3 days. There was visual deficit improvement and total disappearance of spinal cord lesions, but with persistence of motor neurological deficits. Conclusion: This is an unprecedented case report of association between the CHIKV infection and neurologic manifestations: optic neuritis and acute transverse myelitis. Although the association between the arbovirus and demyelinating syndromes is rare it is possible the involvement of the nervous system secondary to the infectious process. If a patient who lives in or who has traveled to an area with endemic CHIKV presents with signs of ATM or ON, the existence of this agent must be investigated. If its presence is confirmed in the blood and/or CSF, in the absence of other causes, its relationship with nervous injury is confirmed.

Intrathecal IGM synthesis in multiple sclerosis and neuromyelitis optica spectrum disorders: Clinical and laboratory analysis

Background: In Multiple Sclerosis (MS), cerebrospinal fluid (CSF) it has been shown to be a useful variable in the evolution and progression of symptoms, being related as a marker of the clinical worsening of the disease. In Neuromyelitis Optica Spectrum Disorders (NMOSD), however, there is still no data on this specific evaluation.

Intrathecal IgM index correlates with a severe disease course in multiple sclerosis: Clinical and MRI results

ObjectivesIntrathecally synthesized IgM can be seen not only in the cerebrospinal fluid (CSF) in infectious and inflammatory diseases of the central nervous system, but also in that of patients with multiple sclerosis (MS). Intrathecal IgM synthesis in MS seems to be correlated with an unfavorable disease course. In one cross-sectional study, intrathecal synthesis of IgM (IgM index) was found to be correlated with cranial magnetic resonance imaging (MRI) parameters. The purpose of this study was to determine the possible relationship between the IgM index and MRI and clinical parameters. Patients and methodsEighty-one patients with MS (58 female) undergoing lumbar puncture were included in the study. Fifty-one patients had a relapsing-remitting (RR) disease course, while 30 cases were secondary progressive MS (SPMS). IgM was detected in paired CSF and serum specimens using ELISA. The IgM index was calculated using the formula CSF IgM/serum IgM: CSF albumin/serum albumin. IgM indexes higher than 0.1 were considered “increased”. All patients underwent brain and whole spinal cord MRI. ResultsThe IgM index was normal in 43 of the 81 patients (53.1%) and increased in 38 (46.9%). A significant correlation was determined between the IgM index and Expanded Disability Status Scale (EDSS) (r=0.638, p=0.001). Most of the subjects with increased IgM indexes were SPMS patients, 28 having a SPMS course and 10 a RRMS course. Only two patients with SPMS courses had normal IgM indexes. EDSS scores were significantly higher in patients with increased IgM indexes (EDSS 4.3 vs EDSS 2.8, p=0.000). All patients with EDSS >3 had increased IgM indexes. All patients with IgM index values higher than 0.2 IgM had SPMS courses and EDSS >6. Time to onset of the secondary progressive phase of the disease was correlated with IgM index values (p=0.004). IgM index values were also correlated with T1 hypointense lesions (r=0.0431, p=0.008) and Gd enhancing lesions (r=0.0396, p=0.006). Patients with increased IgM indexes also had more spinal lesions (p=0.000). No relation was determined between an increased IgM index and an increased IgG index. No relation was determined with IgG oligoclonal band positivity. No correlation was also observed between IgM index and IgG index values. ConclusionAccording to our findings, intrathecal IgM synthesis is associated with a worse long-term prognosis. It also correlates with a higher relapse rate, greater disability, and worse MRI outcomes. Early observation of increased IgM index values will be a helpful tool for clinicians in selecting patients for early immunomodulatory or immunosuppressant treatments.

Cerebrospinal fluid data compilation and knowledge-based interpretation of bacterial, viral, parasitic, oncological, chronic inflammatory and demyelinating diseases. Diagnostic patterns not to be missed in neurology and psychiatry.

The analysis of intrathecal IgG, IgA and IgM synthesis in cerebrospinal fluid (CSF) and evaluation in combined quotient diagrams provides disease-related patterns. The compilation with complementary parameters (barrier function, i.e., CSF flow rate, cytology, lactate, antibodies) in a cumulative CSF data report allows a knowledge-based interpretation and provides analytical and medical plausibility for the quality assessment in CSF laboratories. The diagnostic relevance is described for neurological and psychiatric diseases, for which CSF analysis can't be replaced by other diagnostic methods without loss of information. Dominance of intrathecal IgM, IgA or three class immune responses give a systematic approach for Facial nerve palsy, Neurotrypanosomiasis, Opportunistic diseases, lymphoma, Neurotuberculosis, Adrenoleucodystrophy or tumor metastases. Particular applications consider the diagnostic power of the polyspecific antibody response (MRZ-antibodies) in multiple sclerosis, a CSF-related systematic view on differential diagnostic of psychiatric diseases and the dynamics of brain- derived compared to blood-derived molecules in CSF for localization of paracytes.

Intrathecal lipid-specific oligoclonal IgM synthesis associates with retinal axonal loss in multiple sclerosis

ObjectiveIt has been suggested that autoantibodies may induce axonal damage in multiple sclerosis (MS). Optical coherence tomography (OCT) showed that thinning of peripapillary retinal nerve fiber layer (RNFL) and ganglion cell layer/inner plexiform (GCIPL) measurements reflect axonal loss in the disease. We investigated whether the intrathecal synthesis of lipid-specific oligoclonal IgM bands (LS-OCMB) associates with thinning of these structures in MS patients. Methods58 consecutive MS patients and 70 age-matched healthy controls were assessed. LS-OCMB was studied in cerebrospinal fluid by isoelectric focusing and immunoblotting. RNFL and GCIPL imaging were quantified by spectral domain OCT. ResultsRNFL and GCIPL were significantly reduced in MS patients compared to controls (p<0.01). RNFL thickness was further reduced in LS-OCMB positive MS patients compared to LS-OCMB negative MS subjects mainly in papillomacular bundle (p<0.05), temporal and inferior quadrants (p<0.05) and inferotemporal sector (p=0.01). ConclusionsThe presence of LS-OCMB associates with increased retinal axonal loss in MS. This reinforces the relationship found between the intrathecal synthesis of IgM and the axonal damage observed in immunological and pathological studies even in normal-appearing white matter. OCT seems an optimal tool to monitor axonal damage in LS-OCMB positive patients, relevant for therapeutic decisions and quantification of the effects of new neuroprotective treatments

Application of multiplexing technology to the analysis of the intrathecally released immunoglobulins against B. burgdorferi antigens in neuroborreliosis

Lyme neuroborreliosis (LNB) is an infectious disease of the nervous system caused by the tick-borne spirochete Borrelia burgdorferi. The presence of B. burgdorferi specific antibodies in cerebrospinal fluid (CSF), with evidence of intrathecal production, is the traditional diagnostic standard, although has limitations it such as low sensitivity in the very early phase. In the current study, 27 patients with possible neuroborreliosis suffered from clinically defined Bannwarth syndrome. The control group (CON) consisted of 6 patients. The analyses included function of the blood-CSF barrier (QAlb) as well as intrathecal synthesis of total IgG and IgM, (QIgG, and QIgM). Multiplexing analyses of the specific antibodies (IgG and IgM) against B.burgdorferi antigens were performed with the Microgen assay (Neuried, Germany). The ASI antibodies (Antibody Synthesis Index) specific to particular B. burgdorferi antigens (VlsE, OspC, etc.) were calculated analogously as QIgG and QIgM for separate antibody. All but one patient with NB had pathologic ASI-IgG against B. burgdorferi (median 6.3). Out of 27 NB patients, 13 had measurable ASI-IgM, and all these indices were pathologic. None of the CON subjects had pathologic ASI in either IgG or IgM class. Furthermore, NB patients showed dysfunction of the blood-CSF barrier (average QAlb in the NB and CON groups: 13.8 and 5.6, respectively, p<0.01). Twenty-one of 27 NB patients had at least one positive (>1.5) IgG-ASI against either VlsE, p100, p58, p39, p18, or OspC, and none of these patients showed positive OspA-IgG-ASI. Interestingly, the NB patient with negative IgG ASI on ELISA had the highest p100 IgG ASI on multiplexing (270.8). Among the 13 NB patients with detectable IgM-ASI on ELISA, nine showed measurable IgM-ASI against at least one antigen; however, in one of these cases, the OspC ASI was normal (0.6). In addition, one subject with non-measurable IgM ASI on ELISA had highly pathologic (19.7) index for OspC B. g. on multiplexing. The control subjects with measurable ASI-IgG on ELISA (two cases) had measurable, but normal, indices for VlsE in the IgG class also on multiplexing. None of the control subjects had measurable indices for any of the antigens in the IgM class. The simultaneous analysis of a panel of antibodies against different B. burgdorferi antigens makes multiplexing technology a very interesting supplement to the classic ELISA by providing more specific, antigen-related indices to the general, antigen-unspecific ASI. Whether this additional information proves to be diagnostically relevant will be certainly a matter of further studies.

Intestinal Pseudoobstruction Caused by Chronic Lyme Neuroborreliosis. A Case Report

Chronic intestinal pseudoobstruction is often classified as idiopathic. The condition is associated with poor quality of life and high morbidity, and treatment options are often unsatisfactory. A case of chronic intestinal pseudoobstruction in a 66-year-old woman, presenting with back and abdominal pain, urinary retention and severe constipation is described. The patient lived in an area in which Lyme disease is endemic and had been bitten by ixodes ticks. Intrathecal synthesis of anti-borrelia IgM and IgG and lymphocytosis in the cerebrospinal fluid was found, consistent with chronic Lyme neuroborreliosis since symptoms had lasted for more than six months. The patient’s gastrointestinal function recovered and the pain subsided significantly following treatment with antibiotics. Lyme neuroborreliosis (LNB) often results in palsy, but rarely affects the autonomic nervous system. Three patients have been described with intestinal pseudoobstruction due to acute LNB. However, this is the first described case of intestinal pseudoobstruction due to chronic Lyme neuroborreliosis. LNB must be suspected in patients with intestinal pseudoobstruction, in particular in patients who have been bitten by an ixodes tick and in patients living in an endemic area.

Relation between plasmatic and cerebrospinal fluid oxidative stress biomarkers and intrathecal Ig synthesis in Multiple Sclerosis patients.

The aim of this study was to evaluate if cerebrospinal fluid (CSF) oxidative stress biomarkers were related to plasmatic levels and to intrathecal Ig synthesis in 51 patients with Multiple Sclerosis (MS) or clinically isolated syndrome (CIS). Plasmatic and CSF ferric reducing ability (FRA) showed a significant positive correlation (ρ 0.28, p=0.04), while advanced oxidation protein products (AOPPs) did not. A negative correlation was found between IgG synthesis index and CSF FRA levels. No difference in CSF AOPPs or FRA was observed between patients with and without intrathecal IgM synthesis. Our results indicate that plasmatic and CSF FRA are strictly linked, while CSF oxidative stress biomarkers are not related to intrathecal Ig synthesis.

Lyme neuroborreliosis: a treatable cause of acute ocular motor disturbances in children

BackgroundLyme neuroborreliosis (LNB) designates central nervous system involvement caused by the tick-borne spirochaete Borrelia burgdorferi (Bb). The present study describes a spectrum of acquired ocular motor disorders in children with...

Cerebrospinal fluid immunological biomarkers associated with axonal damage in multiple sclerosis.

Cerebrospinal fluid (CSF) neurofilament light protein (NFL) is a promising biomarker of axonal injury and neurodegeneration. Here CSF lymphocyte subpopulations and antibodies, potential players of neurodegeneration, are examined in relation to CSF NFL shedding in MS. Cerebrospinal fluid NFL from 127 consecutive untreated MS patients was analysed. Samples from 37 age-matched patients with other central nervous system non-inflammatory neurological diseases (NIND) were also assessed. CD4+, CD8+, CD56+ and CD19+ cell subsets were studied by flow cytometry. Oligoclonal IgG and IgM bands (OCMB) against lipids were studied by isoelectric focusing and immunoblotting. These data were analysed in relation to clinical and magnetic resonance imaging features. A CSF NFL cut-off value of 900ng/l (mean+3 SD of NIND values) was calculated. MS patients with increased NFL values showed significantly higher Multiple Sclerosis Severity Score and magnetic resonance imaging lesion number. The presence of OCMB (P<0.0001) and elevated T and B lymphocyte counts was associated with increased levels of CSF NFL. High CSF NFL levels are associated with elevated CSF lymphocyte cell counts and intrathecal synthesis of IgM against lipids. These findings support a role for OCMB in the axonal damage of MS offering a rationale for the association of these antibodies with disability and brain atrophy progression in MS.

Intrathecal IgM production correlates with more severe disease course in multiple sclerosis: Clinical and MRI results

Intrathecally synthesised IgM can be seen not only in the CSF of infectious and inflammatory diseases of the CNS but also in the CSF of patients with multiple sclerosis (MS). In MS intrathecal IgM synthesis seems to correlate with an unfavorable disease course. In a cross-sectional study intrathecal synthesis of IgM (IgM index) was found to be correlated with cranial MRI parameters.

Neurosarcoidosis: Correlation of cerebrospinal fluid findings with diffuse leptomeningeal gadolinium enhancement on MRI and clinical disease activity

BackgroundCerebrospinal fluid (CSF) examination is considered important in the diagnosis of neurosarcoidosis, however, data on whether and how CSF parameters may be related to MRI findings and clinical disease activity of patients with neurosarcoidosis are scarce. ObjectiveTo correlate CSF findings in patients with neurosarcoidosis with MRI findings and clinical disease activity. Material and methodsResults of 51 comprehensive CSF examinations of 25 patients with probable or definite neurosarcoidosis according to the Zajicek-criteria were analyzed retrospectively. ResultsPatients with diffuse leptomeningeal gadolinium enhancement on MRI had significantly higher cell counts (≥50cells/μl in 80%), total protein (≥200mg/dl in 80%), CSF/serum albumin quotients (QAlb, ≥30 in 80%), and lactate (≥30mg/dl in 70%), but significantly lower glucose levels (≤40mg/dl in 67%) than patients without leptomeningeal enhancement. Irrespective of MRI findings, activated lymphocytes and plasma cells were detected in the initial CSF examination in 60% and 47% of patients, and an intrathecal synthesis of IgG, IgA, and IgM in 22%, 29%, and 22%. Patients with clinically active disease had significantly higher CSF cell counts, total protein, QAlb, and lactate, but significantly lower glucose levels than patients with stable disease. ConclusionCSF abnormalities in neurosarcoidosis are most pronounced in patients with diffuse leptomeningeal enhancement on MRI. CSF analyses may thus aid in the distinction of different radiographic and pathologic manifestations of neurosarcoidosis. Furthermore, CSF examinations may allow monitoring disease activity in patients with neurosarcoidosis.

West Nile Virus Meningoencephalitis Imported into Germany

To the Editor: West Nile virus (WNV) is a single-stranded RNA virus in the family Flaviviridae that is transmitted to humans by mosquitoes. Approximately 80% of WNV infections in humans are asymptomatic, whereas ≈20% of infected persons experience fever, often accompanied by a rash. Less than 1% of infections are manifested as neuroinvasive disease, such as meningoencephalitis, polyradiculoneuritis, and polio-like flaccid paralysis (1). WNV is endemic in Africa, southern Asia, and northern Australia, and only sporadic cases or small epidemics are seen in Europe (2). In 1999, WNV emerged in North America. By 2010, ≈1.8 million persons had become infected, with 12,852 reported cases of meningoencephalitis and 1,308 deaths (2). In Europe, the last notable outbreak of WNV infection occurred in Greece in 2010; 197 persons were infected, and 33 died (3). The Czech Republic, Denmark, France, and the Netherlands reported laboratory-confirmed WNV infections in travelers returning from North America (1). We report a case of WNV meningoencephalitis in a 28-year-old German woman, who sought treatment the emergency department of a hospital in Potsdam, Germany, on September 7, 2011. She had a 3-day history of fever of up to 40°C and mental confusion. Six days before admission, she had returned from a 2-week holiday trip to Ottawa, Ontario, Canada. She had spent most of her time in the city of Ottawa. The patient’s medical history was unremarkable. She was in a reduced general condition because of a severe encephalitic syndrome characterized by somnolence, meningism, fever, and mental confusion. Laboratory investigations revealed leukocytosis with 15.000 leukocytes/µL (reference range 4,400–11,300 leukocytes/µL) and elevated C-reactive protein of 14.8 mg/L (reference <3 mg/L). Cerebrospinal fluid (CSF) analysis on the day of admission showed pleocytosis, 430 cells/µL (72% granulocytes, 27% lymphocytes. and 1% monocytes); elevated levels for total protein, 1,023 mg/L (reference range 150–450 mg/L); an albumin level of 637 mg/L (normal range 0–350 mg/L); and a moderately elevated level of the albumin quotient of 20 (reference range <6.5). The CSF/serum diagrams demonstrated a moderate disturbance of the blood–CSF barrier and a substantial intrathecal IgM synthesis of 27.6% (6.15 mg/L) but no intrathecal IgA or IgG synthesis. Results of magnetic resonance imaging of the brain were unremarkable. No parenchymal lesions were found. Antimicrobial drug therapy was initiated with ceftriaxone and ampicillin. Acyclovir was administered empirically for herpes simplex encephalitis until this diagnosis was excluded. Molecular and serologic testing of serum and CSF samples revealed no acute infection with herpesviruses, enteroviruses, alphaviruses, orthobunyaviruses, and arenaviruses or with mycobacteria, Borrelia spp., Toxoplasma gondii, Chlamydia spp., Leptospira spp., and Mycoplasma pneumoniae. CSF and blood cultures were negative for fungi and bacteria, including mycobacteria. An encephalitic syndrome caused by N-methyl-D-aspartate antibodies was also excluded. On the basis of the patient’s travel history, the clinical symptoms, and the initial laboratory findings, WNV infection was suspected. Indirect immunofluorescence assays and virus neutralization tests (VNT) for WNV and other flaviviruses were performed as described (4). IgM and IgG against WNV were detected in serum and in CSF by indirect immunofluorescence assay with an 8-fold (IgM) and 32-fold (IgG) increase in serum titer from day 4 to day 26 (Table). WNV IgG and WNV IgM titers were higher than the titers of antibodies against the other flaviviruses tested (Table), indicating that the antibodies resulted from a WNV infection. The serologic diagnosis was further substantiated by detection of WNV neutralizing antibodies at day 11 (VNT titer 640). The VNT titer further increased to 2,560 on day 26 after onset of disease. Results of reverse transcription PCR were negative for WNV and members of genus Flavivirus in serum and CSF samples taken 4 days after disease onset. Attempts to isolate WNV from serum and CSF samples in cell culture failed as well. The patient recovered slowly and was discharged from the hospital in Potsdam on September 15, 2011. She was then referred to a neurologic rehabilitation center in Berlin and was discharged from there after 2 months with a characterization of restitutio ad integrum (i.e., full recovery, restoration to original condition). Table Results of indirect immunofluorescence assays performed on serum and CSF samples from patient with suspected WNV infection, Germany, 2011* We report a case of WNV infection imported into Germany that was unambiguously confirmed by laboratory testing. WNV meningoencephalitis was diagnosed on the basis of strict serologic criteria established by the Centers for Disease Control and Prevention (Atlanta, GA, USA) (5). In 2011, 69 clinical cases of WNV infection were reported from the province of Ontario, although no cases in the city of Ottawa were reported (Public Health Agency of Canada; www.eidgis.com/wnvmonitorca). This imported case adds to these cases and suggests that travelers are at risk, even if they visit only Ottawa. Physicians in Germany should be aware of the risk for WNV infection among travelers returning from Canada, especially during late summer.

Axonal and oligodendrocyte-localized IgM and IgG deposits in MS lesions

BackgroundRecent findings support the important role of antibodies in multiple sclerosis (MS) physiopathology. Thus, local IgG synthesis is a hallmark of the disease, and intrathecal IgM synthesis associates with a poor disease outcome. MethodologyThe aim of this study was to investigate the presence of IgM and IgG in demyelinating lesions using high sensitivity immunohistochemistry techniques in necropsies from fourteen MS patients, four controls without neurological disease and four cases with non MS CNS inflammatory disease. ResultsIgG and IgM were absent in controls. Conversely, we found IgM in about 50% and IgG in 75% of MS patients. The presence of IgM and IgG antibodies was independent of disease duration, clinical disease type or lesion stage. IgM and IgG were present in acute, chronic active and chronic inactive lesions. Double immunofluorescence showed that IgM and IgG were detected on axons and oligodendrocytes in demyelinated areas. Moreover, we observed immunoglobulin deposits on oligodendrocytes in NAWM in some cases. IgG and IgM colocalized with complement C3b on demyelinated axons and oligodendrocytes and antibody–antigen immunocomplexes were detected in foamy macrophages in active lesion areas. These findings were absent from cases of non-neurological disease and cases with non-MS CNS inflammatory disease. Significance of the studyThese observations provide further evidence on the role of antibodies, complement and macrophages in plaque development, and strongly suggest they can induce axonal injury, an important cause of disability in MS. They may provide novel therapeutic strategies to limit tissue degeneration in the disease.

Downregulation of Intrathecal IgM Synthesis Associates with Optimal Response to Natalizumab in Multiple Sclerosis (P06.175)

Downregulation of Intrathecal IgM Synthesis Associates with Optimal Response to Natalizumab in Multiple Sclerosis (P06.175)

Quantitative MRI and Cerebrospinal Fluid Inflammatory Mediators in Brazilian Patients with Relapsing-Remitting Multiple Sclerosis before and after Treatment with Immunomodulators: A Longitudinal Study

Objective: The pathological hallmarks of multiple sclerosis (MS) lesions are inflammation, demyelination, axon loss and gliosis. The aim of this study was to verify the relation of brain lesion load and volume of the cerebral hemisphere determined by brain MRI with intrathecal antibody synthesis. Methods: A longitudinal study of 54 Brazilian patients with the relapsing-remitting form of MS was undertaken after an average of 6.3 ± 2.7 years of treatment. MRI scans were performed, and cerebrospinal fluid samples were collected both during the diagnostic process and after treatment with β-interferon or glatiramer acetate. Results: A positive correlation between the IgG index and total lesion volume was identified. Intrathecal IgG against Epstein-Barr virus (EBV) was observed in 21 patients. The number of contrast-enhanced lesions observed in these patients was correlated with intrathecal IgM synthesis. Brain atrophy was observed early in the disease, with the number of relapses inversely correlated with brain volume. Conclusion: The high intrathecal IgG synthesis observed in these relapsing-remitting MS patients is associated with the brain lesion burden and the presence of antibodies to EBV, whereas intrathecal IgM synthesis is associated with the activity of the disease, as revealed by MRI.

Intrathecal synthesis of IgM measured after a first demyelinating event suggestive of multiple sclerosis is associated with subsequent MRI brain lesion accrual

Background: Previous studies have demonstrated that intrathecal synthesis of IgM is observed in multiple sclerosis (MS) and correlates with a worse disease course. These results suggest that IgM participates in the formation of MS lesions. Objective: The aim of the present study was to assess the potential association between the level of intrathecal synthesis of IgM measured after a clinically isolated syndrome (CIS) and the subsequent formation of brain lesions. Methods: Fifty seven patients with a CIS and a high risk developing MS were enrolled in a longitudinal study. Examination of cerebrospinal fluid was performed after the CIS and included measures of intrathecal IgM and IgG synthesis. Patients were assessed with the same 1.5 Tesla magnetic resonance imaging (MRI) system at baseline and after a mean follow-up period of 49 months (range 36–60). Spearman Rank correlation was used to assess the potential correlations between levels of intrathecal immunoglobulin synthesis and MRI data. Results: The level of intrathecal IgM synthesis was correlated with the number of gadolinium-enhancing lesions at baseline (p = 0.01) and with accrual of brain lesions during the follow-up period (p = 0.02). By taking into account brain sub-regions, we demonstrated that the level of intrathecal IgM synthesis was only correlated with the increased number of lesions in the periventricular regions (p = 0.004). The level of intrathecal IgG synthesis was not correlated with any MRI data. Conclusion: The present longitudinal study demonstrates that the level of intrathecal IgM synthesis measured after a CIS is associated with subsequent lesion accrual during the first years of MS. This result emphasizes the involvement of IgM in plaque formation.

Clinicopathological considerations in acute disseminated encephalomyelitis (ADEM): a fulminant case with favorable outcome

We report the clinical course and pathological features of a 52-year-old woman with fulminant acute disseminated encephalomyelitis (ADEM). She presented with subacute tetraparesis, which developed over 2 days, and progressive loss of consciousness. CCT showed pronounced bihemispherical and periventricular edema. Multifocal glioma was suspected, and the patient was referred for brain biopsy to the neurosurgery department at our hospital. On admission, the patient presented with progressive tetraparesis and aphasia. Subsequently, she developed epileptic seizures. Cranial magnetic resonance imaging (MRI) revealed confluent bihemispherical and periventricular white matter edema (Fig. 1a) with abnormal patchy gadolinium enhancement, compatible with progressive multifocal leukoencephalopathy (PML), multifocal brain tumor or ADEM. Cerebrospinal fluid (CSF) analysis revealed mild pleocytosis (11 cells/ll) with increased protein levels, and normal glucose and lactate levels. No intrathecal IgG and IgM synthesis or oligoclonal bands (OCB) were observed in CSF. Antiviral and antibiotic treatment was initiated. Stereotactic brain biopsy from right frontal periventricular white matter (Fig. 1b) was performed 5 days after disease onset. Histopathology ruled out malignant brain tumor but showed acute perivascular inflammation.

Neuroimmunological findings of Angiostrongylus cantonensis meningitis in ecuadorian patients

Meningitis caused by Angiostrongylus cantonensis has recently been reported in patients resulting from the first outbreaks in subtropical regions of Ecuador. Eight young adult patients from the two outbreaks were studied. IgA, IgM, IgG and albumin in cerebrospinal fluid and serum were quantified and plotted in cerebrospinal fluid/serum quotient diagrams (Reibergrams). The anamnesis on the patients included asking about any consumption of raw snails, symptoms and harm caused. Mean eosinophilia of 7.5% and 26% in serum and cerebrospinal fluid respectively was observed, as well as a moderate increase in total proteins. The most frequent pattern of intrathecal synthesis was observed in three classes of immunoglobulins. Intrathecal synthesis of IgM was observed in all cases two weeks after the first symptoms appeared. The intrathecal synthesis patterns of eosinophilic meningitis due to Angiostrongylus cantonensis, facilitated by cerebrospinal fluid analysis, were similar to those of previous cases from abroad.

Comparison of Major Immunoglobulins Intrathecal Synthesis Patterns in Ecuadorian and Cuban Patients with Angiostrongyliasis

Angiostrongylus cantonensis meningitis was first reported in Cuba in 1981, and it was recently reported in South America. The aim of this paper is to evaluate the intrathecal immunoglobulin synthesis patterns from Cuba's and Ecuador's patients with angiostrongyliasis; 8 Ecuadorian patients from two different outbreaks and 28 Cuban patients were studied. Simultaneous blood and cerebrospinal fluid samples were taken. Immunoglobulin (Ig) A, IgM, IgG, and albumin were quantified by radial immunodiffusion. Corresponding Reibergrams were applied. A three-Ig pattern was the most frequent in the two groups, but IgM was presented in all Ecuadorian young mature patients; however, in the Cuban children, only 12 of 28 patients had intrathecal IgM, but about 90% had an IgA and IgG synthesis at time of later puncture. This indicates that, with a larger amount of parasites ingested, clinical symptoms are more severe, and a higher frequency of intrathecal IgM synthesis could be observed. This is discussed as a similarity with the intrathecal IgM synthesis in African trypanosomiasis.