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Objective: To evaluate the performance of serum neurofilament light chain (NfL) and cerebrospinal fluid (CSF) phosphorylated neurofilament heavy chain (pNfH) as diagnostic biomarkers for the differentiation between motor neuron disease (MND) and multifocal motor neuropathy (MMN)., Methods: This retrospective, monocentric study included 16 patients with MMN and 34 incident patients with MND. A subgroup of lower motor neuron (MN) dominant MND patients (n = 24) was analyzed separately. Serum NfL was measured using Ella automated immunoassay, and CSF pNfH was measured using enzyme-linked immunosorbent assay. Area under the curve (AUC), optimal cutoff values (Youden's index), and correlations with demographic characteristics were calculated., Results: Neurofilament concentrations were significantly higher in MND compared to MMN (p < 0.001), and serum NfL and CSF pNfH correlated strongly with each other (Spearman's rho 0.68, p < 0.001). Serum NfL (AUC 0.946, sensitivity and specificity 94%) and CSF pNfH (AUC 0.937, sensitivity 90.0%, specificity 100%) performed excellent in differentiating MND from MMN. Optimal cutoff values were ≥ 44.15 pg/mL (serum NfL) and ≥ 715.5 pg/mL (CSF pNfH), respectively. Similar results were found when restricting the MND cohort to lower MN dominant patients. Only one MMN patient had serum NfL above the cutoff. Two MND patients presented with neurofilament concentrations below the cutoffs, both featuring a slowly progressive disease., Conclusion: Neurofilaments are valuable supportive biomarkers for the differentiation between MND and MMN. Serum NfL and CSF pNfH perform similarly well and elevated neurofilaments in case of diagnostic uncertainty underpin MND diagnosis., (© 2024. The Author(s).)

Introduction: Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is an increasingly recognized type of steroid-responsive autoimmune disease of the nervous system. Defined in 2016, it is associated with the presence of anti-GFAP immunoglobulinG in the serum or cerebrospinal fluid (CSF) of affected patients., Patient Characteristics: Herein, we report a case of acute neurological symptoms, including headache, fever, confusion, and paralysis of the lower extremities. CSF analysis revealed lymphocytic pleocytosis and elevated protein levels, indicating acute disseminated encephalomyelitis, and the patient was given immunotherapy. Cranial magnetic resonance imaging showed multifocal T2/fluid-attenuated inversion recovery hyperintense signal changes in the periventricular white matter, and electromyography testing showed changes consistent with severe sensorimotor neuropathy, indicating the involvement of the brain and peripheral nerves., Diagnoses: Finally, a diagnosis of autoimmune GFAP astrocytopathy was confirmed due to the presence of GFAP-immunoglobulinG in the patient's CSF., Interventions: The patient was treated with one course of intravenous immunoglobulin therapy, then followed with intravenous methylprednisolone (1.0 g/d for 3 days) and oral prednisolone., Outcomes: At 1 week after intravenous immunoglobulin therapy, his level of consciousness improved. However, flaccid paralysis persisted without substantial improvement., Conclusion: In conclusion, the provision of an accurate early diagnosis and appropriate treatment are crucial for improving the prognosis of patients with autoimmune GFAP astrocytopathy. Further, this case highlights the importance of recognizing the role of peripheral nerve involvement in GFAP autoimmunity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Chronic autoimmune demyelinating polyneuropathies (CADP) result in impaired sensorimotor function. However, anecdotal clinical observations suggest the development of cognitive deficits during the course of disease., Methods: We tested 16 patients with CADP (11 patients with chronic inflammatory demyelinating polyneuropathy, 4 patients with multifocal motor neuropathy and 1 patient with multifocal acquired demyelinating sensory and motor neuropathy) and 40 healthy controls (HC) with a neuropsychological test battery. Blood-brain-barrier dysfunction (BBBd) in patients was assessed retrospectively by analysing the cerebral spinal fluid (CSF) status at the time the diagnosis of CAPD was established., Results: CADP patients failed on average in 1.7 out of 9 neuropsychological tests (SD ± 1.25, min. 0, max. 5). 50% of the CADP patients failed in at least two neuropsychological tests and 44.3% of the patients failed in at least two different cognitive domains. CADP patients exhibiting BBBd at the time of first diagnosis failed in more neuropsychological tests than patients with intact integrity of the BBB (p < 0.05). When compared directly with the HC group, CADP patients performed worse than HC in tests measuring information processing ability and speed as well as phonemic verbal fluency after adjusting for confounding covariates., Conclusions: Our results suggest that mild to moderate cognitive deficits might be present in patients with CAPD. One possible tentative explanation, albeit strong evidence is still lacking for this pathophysiological mechanism, refers to the effect of autoimmune antibodies entering the CNS via the dysfunctional blood-brain barrier typically seen in some of the CADP patients., Competing Interests: Yavor Yalachkov has been supported by travel grants from Novartis and Sanofi Genzyme, has received an honorarium for active participation in an advisory board by Sanofi Genzyme as well as a speaking honorarium by Roche. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

This pilot study was designed to compare the levels of interleukin-8 (IL-8), a pro-inflammatory chemokine, in the cerebrospinal fluid (CSF) of patients with Guillain-Barre syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), non-inflammatory polyneuropathy (PNP), and other non-inflammatory neurological diseases (functional syndrome or migraine). The results show elevated CSF IL-8 levels in GBS compared to the other groups (p < 0.05). IL-8 could be considered a potential biomarker to differentiate GBS from CIDP. This distinction could be relevant in terms of therapeutic decisions and functional prognosis.

Objective: Insulin-like growth factors (IGFs) have neuroprotective effects. IGF activity is partly controlled by pregnancy-associated plasma protein-A (PAPP-A), an enzyme which enhances IGF-action by cleavage of IGF-binding protein-4 (IGFBP-4). To study the role of PAPP-A and the IGF system in diabetic polyneuropathy (DPN), we measured immunoreactive (total) concentrations of IGF-I and IGF-II, bioactive IGF by cell-based bioassay, PAPP-A, as well as intact and PAPP-A-cleaved IGFBP-4 in cerebrospinal fluid (CSF) and serum from patients with type 2 diabetes (T2D) with and without DPN., Design: Twenty-three patients with T2D were included. Based on clinical examination, vibratory perception thresholds and nerve conduction studies, patients were diagnosed with (n = 9) or without (n = 14) DPN., Results: In CSF, PAPP-A activity, as estimated by IGFBP-4 fragment levels, was higher in patients with than without DPN (34.57 vs 13.79 μg/L, p = .003) and concentrations correlated with peripheral nerve impairment measures (r = 0.73, p < .01). Furthermore, serum bioactive IGF was lower in patients with than without DPN (0.8 vs 1.3 μg/L, p = .006) and correlated inversely to the severity of DPN (r = -0.67, p < .01)., Conclusions: In both CSF and serum, members of the IGF system correlated with measures of peripheral nerve impairment in patients with T2D. This supports a relationship between the IGF system and the development of DPN. Further studies are needed to clarify if these changes are causally linked to the pathogenesis of DPN., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Importance: A clearer definition of the role of neurofilament light chain (NFL) as a biomarker in amyotrophic lateral sclerosis (ALS) is needed., Objectives: To assess the ability of NFL to serve as a diagnostic biomarker in ALS and the prognostic value of cerebrospinal fluid NFL in patients with ALS., Design, Setting, and Participants: In this single-center, retrospective, longitudinal study, disease progression was assessed by the ALS Functional Rating Score-Revised and the ALS Milano-Torino Staging system at baseline and 6, 12, 24, and 36 months. Cerebrospinal fluid samples were obtained from 176 patients admitted to the Department of Neurosciences of the University of Padua, Padova, Italy, from January 1, 2010, through February 29, 2016. Patients with ALS underwent ambulatory follow-up at the same department., Main Outcomes and Measures: Levels of NFL., Results: The study included 94 patients with ALS (64 men [36.4%] and 30 women [17.0%]; median age, 62.5 years), 20 patients with frontotemporal dementia (FTD) (8 men [4.5%] and 12 women [6.8%]; median age, 65 years), 18 patients with motor neuropathies (14 men [8.0%] and 4 women [2.3%]; median age, 63 years), and 44 controls (24 men [13.6%] and 20 women [11.4%]; median age, 54 years). Log-transformed NFL (log[NFL]) concentrations were higher in the ALS and FTD groups compared with the motor neuropathies and control groups (hazard ratio [HR], 2.45; 95% CI, 1.66-3.61; P < .001). Patients with typical ALS (HR, 1.0 [reference]), progressive bulbar palsy (HR, 1.48; 95% CI, 0.58-3.75; P = .41), and upper motor neuron dominant ALS (HR, 0.12; 95% CI, 0.02-0.61; P = .01) had higher levels of NFL than did those with flail arm or leg syndrome (HR, 0.28; 95% CI, 0.08-0.10; P = .049) and progressive muscular atrophy (HR, 0.17; 95% CI, 0.22-1.36; P = .10). There was an inverse correlation between log[NFL] concentration and overall survival (HR, 2.45; 95% CI, 1.66-3.61; P < .001). There was no evidence of different log[NFL] concentrations and survival in genetic ALS., Conclusions and Relevance: This study confirms the role of NFL as a biomarker in ALS. Elevation in NFL levels in patients with upper motor neuron involvement and FTD might reflect the corticospinal tract degeneration. Low NFL levels in patients with lower motor neuron signs might be a prognostic indicator of milder phenotypes of disease.

Amyotrophic lateral sclerosis (ALS) is diagnosed on the basis of progressive symptoms in both the upper and lower motor neurons. Because there are no specific biomarkers for ALS, it is difficult to diagnose this disease in its early stages. Cerebrospinal fluid (CSF) samples were obtained from 14 patients in the early stages of ALS, from 13 with polyneuropathy, and from 16 with other neurological disorders. The concentration of cystatin C in the CSF was measured using a sandwich enzyme-linked immunosorbent assay (ELISA) kit. The concentration of cystatin C in the CSF was significantly lower in ALS patients than in the control subjects who were patients with polyneuropathy or other neurological diseases (patients with ALS, polyneuropathy, and other diseases exhibited 5.5 +/- 0.3, 6.7 +/- 0.4, and 6.9 +/- 0.3 mg/L cystatin C, respectively; ALS patients vs. control subjects: p = 0.014 and ALS patients vs. polyneuropathy patients: p = 0.024). Cystatin C may be a useful biomarker of ALS and can be used to distinguish between ALS and polyneuropathy.

Background: Pain is a common symptom in polyneuropathies (PNPs), although it is still not known why some PNPs are painful and others are painless. Increased pro-inflammatory cytokines have been found in conditions resulting in exaggerated pain states in animal studies. Recently, elevated pro-inflammatory cytokine levels have also been found in the cerebrospinal fluid (CSF) of patients suffering from complex regional pain syndrome. Pro-inflammatory cytokines have been shown to induce or increase inflammatory or neuropathic pain., Methods: Using chemiluminescent enzyme immunometric assays, cytokine levels in 36 patients with painful and painless non-inflammatory PNPs in serum and CSF were investigated. The severity of PNPs was measured with electroneurography (ENG). In subjects with normal results using conventional ENG, quantitative thermo-testing was performed to investigate small-nerve-fibre function., Results: Interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha in serum or CSF did not differ between patients with (n = 18) or without (n = 18) painful PNPs, whereas patients with mechanical allodynia (n = 5) had elevated serum TNF-alpha levels compared to those without allodynia. TNF-alpha and IL-6 serum levels were higher in patients with severe (n = 21) compared to those with mild neuropathy (n = 15), and showed a positive correlation with severity of neuropathy., Conclusions: Results suggest that nerve fibre degeneration and presence of mechanical allodynia in peripheral non-inflammatory neuropathy determine cytokine expression in serum.

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.

Infection of the peripheral nervous system with Borrelia burgdorferi can present as a cranial neuropathy or radiculopathy with cerebrospinal fluid (CSF) pleocytosis and intrathecal antibody production against B. burgdorferi, or as an asymmetric peripheral neuropathy with acrodermatitis chronica atrophicans (ACA) and normal CSF findings. According to North American studies, it can also present as a symmetric chronic polyneuropathy without ACA or other Lyme manifestations. Our purpose was to investigate the prevalence of B. burgdorferi antibodies in patients presenting with isolated chronic polyneuropathy (PN) in a European region with high incidence of Lyme disease. Sera from 209 PN patients and 247 healthy blood donors from Vest-Agder County, Norway, were examined. Borrelia burgdorferi antibodies were detected in 43 (21%) PN patients and in 45 (18%) healthy blood donors (P = 0.553). The prevalence of B. burgdorferi antibodies was similar (P = 0.311) in cryptogenic PN (24/102, 24%) and PNs of identified etiologies (19/107, 18%). PN patients with B. burgdorferi antibodies had normal spinal fluid white cell count and they did not differ clinically or electrophysiologically from PN patients without antibodies. None of 20 antibody-positive PN patients responded to antimicrobial treatment. The study shows that, in Europe, chronic distal PN without ACA or other Lyme manifestations is very rarely caused by a B. burgdorferi infection.

The side chain oxidized oxysterol 24S-hydroxycholesterol (24-OH-chol) is formed almost exclusively in the brain, and there is a continuous passage of this oxysterol through the circulation to the liver. 27-Hydroxycholesterol (27-OH-chol) is produced in most organs and is also taken up by the liver. The 27-OH-chol-24-OH-chol ratio is about 0.1 in the brain and about 2 in the circulation. This ratio was found to be about 0.4 in cerebrospinal fluid (CSF) of asymptomatic patients, consistent with a major contribution from the circulation in the case of 27-OH-chol. In accordance with this, we demonstrated a significant flux of deuterium labeled 27-OH-chol from plasma to the CSF in a healthy volunteer. Patients with a defective blood-brain barrier were found to have markedly increased absolute levels (up to 10-fold) of both 27-OH-chol and 24-OH-chol in CSF, with a ratio between the two sterols reaching up to 2. There was a significant positive correlation between the levels of both oxysterols in CSF and the albuminCSF-albuminplasma ratio. The 27-OH-cholCSF-24-OH-cholCSF ratio was found to be about normal in patients with active multiple sclerosis and significantly increased in patients with meningitis, polyneuropathy, or hemorrhages. Results are discussed in relation to the possible use of 24-OH-cholCSF as a surrogate marker of central nervous system demyelination and/or neuronal death.

The results of subclinical brain damage study of 20 patients with inflammatory demyelinating polyneuropathy, aged 46.5 +/- 3.7 years, are presented. Eleven patients were diagnosed to have Guillain--Barre syndrome and 9--chronic inflammatory demyelinating polyneuropathy. No clinical systems for central nervous system damage were found. Magnetic resonance tomography defected demyelination foci in periventricular and sub-cortical brain regions in 35% of the patients and diffuse atrophic process--in 55%. Registration of brainstem acoustic-evoked potentials showed bilateral latency increase and a change of a signal shape in 60% of the patients. Possible mechanisms of combined damage of central and peripheral nervous system in this pathology are discussed.

Immunosorption of cerebrospinal fluid with updated "Pall" immunofilters (Germany) was successfully performed in 3 patients with progressing hormone-resistant Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy. It was proved that clinical improvement in the patients' state correlated with a decrease in the contents of both total protein and immunoglobulins G, A, M in cerebrospinal fluid. It was suggested that the removal of these humoral factors had decreased a degree of inflammatory and demyelinating processes in inflammatory demyelinating polyneuropathies and had improved, thereby, the results of the treatment.

We developed a double sandwich immunoassay for the dosage of ciliary neurotrophic factor (CNTF) in cerebrospinal fluid (CSF). The detection limit was 100 pg/ml. This assay was applied to human CSF samples from 14 normal subjects, 26 patients with multiple sclerosis (MS), 17 with Guillain-Barré syndrome (GBS) or chronic inflammatory demyelinating polyneuropathy (CIDP), and 22 with tumours of the central nervous system (CNS) or leucaemic meningosis (LM). Samples from normal control subjects and from patients with tumours did not contain detectable CNTF. Only 2 patients with LM were positive, and all the patients with inflammatory diseases of the CNS and peripheral nervous system were positive. The MS group presented a mean value of 240 pg/ml CNTF and the GBS/CIDP group a value of 430 pg/ml.

High titers of antibodies directed against gangliosides, especially GM1, are found in the serum of patients with a variety of polyneuropathies, including those of the inflammatory type. We assayed anti-GM1 IgG and IgM levels in the serum and cerebrospinal fluid (CSF) of 23 patients with Guillain-Barré syndrome (GBS) and 10 with chronic inflammatory demyelinating polyneuropathy (CIDP) to investigate whether this immune response may also be localized within the intrathecal compartment and correlate with clinical parameters such as time interval since disease onset, disability score, preceding infectious episodes, and GM1 therapy. When compared to the control group, anti-GM1 IgG was increased in the serum of 39% of GBS and 10% of CIDP patients, whereas anti-GM1 IgM was elevated in 17% of GBS and none of the CIDP patients. In both patient groups, however, anti-GM1 antibody levels were more frequently elevated in CSF than paired sera: they belonged to the IgG class in 48% of GBS and 50% of CIDP patients, and to the IgM class in 48% of GBS and 55% of CIDP patients. In the GBS group, anti-GM1 IgM serum levels inversely correlated with time elapsed between sample collection and onset of disease (P < 0.05), whereas serum anti-GM1 IgG levels positively correlated with the loss of functional ability (P < 0.005). Increased anti-GM1 antibodies in GBS serum were not associated with clinical or serological evidence of infectious antecedents nor with previous GM1 treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Cyclic adenosine 3',5'-monophosphate (cAMP) and cyclic guanosine 3',5'-monophosphate (cGMP) were measured in cerebrospinal fluid (CSF) and plasma from 7 patients with bacterial meningitis, 9 patients with serous meningitis, 5 patients with idiopathic polyneuritis and 15 reference patients. A significantly (P less than 0.01) higher mean concentration of CSF cAMP was found in serous meningitis (33.8 +/- 12.5 nmol/l) compared to the reference group (20.2 +/- 4.0 nmol/l). No significant difference could be observed between the patients with purulent meningitis compared to the reference group. The CSF cAMP concentration (11.0 +/- 2.8 nmol/l) for idiopathic polyneuritis was significantly (P less than 0.01) lower than in the reference group. No difference in CSF levels of cGMP or in the cAMP/cGMP ratios were detected between the groups. Our data suggest that the ratio between cAMP concentrations in CSF and plasma may aid in the differential diagnosis between serous and purulent meningitis.

Immune complexes (IC) were assessed in serum and CSF from 11 patients with acute inflammatory polyneuritis (AIP). An 125 I-labeled Clq binding assay (Clq BA) was used. IC were present in the sera of four patients and in the CSF of six. CSF-Clq BA of AIP (Group 1) were compared with 12 patients with other inflammatory neurological diseases (Group 2) and 22 patients with non-inflammatory neurological diseases (Group 3). There was only a significant difference between Group 1 compared to Group 3 (p less than 0.05). Serum and CSF IC did not correlate either with blood-brain barrier lesions or with immunoglobulin deposits in sural nerve biopsy.

A method for the preparation of a potent and specific peroxidase-labelled antihuman IgG antibody is described. CSF cells from patients with various neurological diseases were stained. Only in cases of inflammatory diseases was IgG detectable. The stained cells were so-called lymphoid cells. As the demonstrable IgG can be regarded as a product of intracellular synthesis, it is justified to call these cells activated B lymphocytes. The relative portion of activated B cells tends to be high in the first half of the mononuclear phase and depends upon the type of disease. It is low in most cases of bacterial and benign viral meningitis whereas high B cell numbers were found in Bannwarth meningopolyneuritis, mumps meningitis and herpes simplex encephalitis. Albeit there exists a time lag between the maximal number of activated B lymphocytes and the demonstration of the secretory immunoglobulin fraction, quantitative correlation between these two inflammation parameters were demonstrated in cases of acute meningoencephalitis. These correlations were not seen in chronic inflammatory diseases.

High-resolution agarose gel electrophoresis, combined with immunofixation electrophoresis, was used to detect and identify immunoglobulins in the cerebrospinal fluid of six patients with paraproteinemic polyneuropathy. In four patients with serum IgM kappa monoclonal protein, we found a discrete band in the cerebrospinal fluid identified also as IgM kappa; one patient with serum IgG kappa had an IgG kappa cerebrospinal fluid band, and one patient with serum IgA kappa had an IgA kappa monoclonal band in the cerebrospinal fluid. The permeability of the blood-cerebrospinal fluid barrier was increased 3 to 10 times in all these patients. The findings indicate that in patients with paraproteinemic polyneuropathy, the increased permeability of the blood-cerebrospinal fluid barrier results in influx of serum proteins into the cerebrospinal fluid, including high-molecular-weight IgM. Because monoclonal IgM, unlike monoclonal IgG and IgA, is not found in the cerebrospinal fluid of neurologically intact patients, its presence in the cerebrospinal fluid of patients with paraproteinemias should lead the physician to suspect neurological involvement and can be of diagnostic value.

In this review we have tried to indicate the potential importance and interest of the proteins of the CSF and have argued that only by electrophoresis can these be examined in context. Without the need for expensive or elaborate equipment, a small volume of CSF can be used to demonstrate the pattern of proteins present, various qualitative changes, and the amounts of some individual proteins. For routine work this is of practical help in the diagnosis of certain neurological conditions, and as a research tool it can be utilized to investigate changes in protein structure and function occurring as part of immune or other responses. Access to neural tissue is necessarily restricted, but there is a great deal to be learned from the CSF.

Unconcentrated cerebrospinal fluid (CSF) and corresponding serum from 30 patients with multiple sclerosis (MS), 30 with other neurological disease and 30 controls suffering from tension headache or psychoneurosis, were examined for oligoclonal IgG bands by initial separation employing agarose isoelectric focusing (AIF) followed by a modified procedure of immunofixation with monospecific antiserum and silver staining. This method is specific for demonstration of IgG and has a limit for detection of 0.4 microgram of IgG. Comparing the results with those obtained by AIF followed by capillary blotting to nitrocellulose membrane, double antibody peroxidase labeling and avidin-biotin amplification, both methods revealed similar frequencies of positive findings for oligoclonal IgG bands in the three patient groups. AIF followed by antiserum immunofixation and silver staining is a simple, sensitive and specific method for detection of oligoclonal IgG in unconcentrated CSF.

Clinical data of 19 patients with meningopolyneuritis Garin-Bujadoux-Bannwarth (MPN-GBB), treated with 2 X 10 million units intravenous sodium penicillin for 10 days, were evaluated at the beginning of therapy, 3 weeks thereafter, and 6 months after onset of the neurological disease. Cerebrospinal fluid (CSF) was analysed in 14 patients at the onset of therapy and 3 1/2 weeks thereafter. At the same interval antibodies against B. burgdorferi were measured by enzyme-linked immunosorbent assay (ELISA) in the CSF and sera of 12 patients. Clinical data and all CSF results, with exception of specific antibody titers, were compared with those of patients who had suffered from MPN-GBB between 1979 and 1983, and who had not received antibiotic or corticosteroid therapy. Comparing the clinical data of all treated patients with those of all non-treated controls, no significant difference could be observed. A significant improvement could however be detected in those patients who had their treatment begun 5 weeks within onset of the neurological disease. Changes in CSF 3 1/2 weeks after onset of treatment showed slight differences when compared with controls.

In order to establish the diagnostic value of clinical chemical analyses of C.S.F. samples, the C.S.F. data from seven hundred patients have been evaluated. The authors discuss the influence this investigation has exerted on their differential diagnostic evaluation.

Detection of intrathecally produced antibodies in cerebrospinal fluid (CSF) of patients with meningopolyneuritis Garin-Bujadoux-Bannwarth (MPN-GBB) is well documented. Analysis of CSF has revealed the oligoclonal nature of these antibodies. We investigated oligoclonal antibodies (OA) in CSF and serum of MPN-GBB patients with regard to immunoglobulin class, light chain type and specificity and compared the findings with those in other neurological diseases (OND). For this purpose an immunofixation (IF) technique after agarosegel electrophoresis (AE) of concentrated CSF was used. 87% of patients with MPN-GBB demonstrated in the acute stage of their disease oligoclonal bands (OB) in their CSF which could not be detected in paired serum samples. IF revealed in most cases of MPN-GBB IgG banding. While IgM banding was a common finding in CSF of MPN-GBB patients, this was not the case in OND. Specificity of CSF OA against components of Borrelia burgdorferi could be demonstrated by agarose isoelectric focusing (AIEF), transfer to nitrocellulose paper and reaction with 125I labelled B. burgdorferi antigen.

Cerebrospinal fluid (CSF)/serum concentration gradients (Q) of individual proteins (albumin, IgG, alpha 2-macroglobulin) have been studied in controls and in patients in whom the lumbar CSF flow is altered (medullary compression) or the blood-CSF barrier (BCB) function impaired (acute idiopathic polyneuropathy and acute meningoencephalitis). The analysis of relationships among protein Q has been performed by total and multiple regressions and the actual BCB permeability to individual proteins has been interpreted according to the accepted theoretical porous or vesicular BCB models. The exponential Q-IgG vs. Q-albumin total regression, and the poor Q-alpha 2-macroglobulin vs. Q-albumin regression found in controls, together with the different multiple regressions among proteins and the high Q-IgG vs. Q-albumin partial regression coefficients found in medullary compression, acute idiopathic polyneuropathy and acute meningoencephalitis, indicated that different permeability mechanisms can be postulated. Heterogeneous, fairly independent permeability BCB mechanisms maintain the normal CSF/serum protein concentration gradient. Pinocytotic vesicles or pores of radius exceeding 1000-1500 A, probably located at the capillary endothelium, account for the main serum-derived CSF protein fraction(s) with large hydrodynamic radius (R). A more selective endothelial vesicular transport with a radius of 250 A transfers a negligible amount of protein from serum into CSF. Proteins with small R also enter the CSF through a set of selective pores of radius 120 A, probably at the level of the choroidal epithelium. Pinocytotic vesicles with a radius of 250 A and increased rate of formation induce the accumulation of proteins below an obstruction of lumbar CSF flow. An increased formation rate of vesicles with a radius of 450 A can explain the increased capillary permeability in nerve roots in acute idiopathic polyneuropathy. Loss of selectivity was the main feature of BCB in acute meningoencephalitis, and it seemed to be due to pores or vesicles with a radius larger than 1000-1500 A. The heterogeneity of BCB mechanisms must be taken into account when the intrathecal synthesis of a protein, also derived from serum (for example IgG), has to be measured.

Fifty patients with acute idiopathic polyneuritis have been studied clinically and electromyographically, and sural nerve biopsy was performed on 8 patients. Motor and sensory conduction studies were within the normal range in 7 patients (14%), and there was pronounced slowing of motor conduction in 25 patients (50%). There was no apparent correlation between the degree of conduction, and the clinical disability of the patient or the duration of the acute illness. Eighteen patients were re-examined at intervals up to 5 1/2 years after the onset of their illness. Eight patients (44%) were clinically normal at follow-up examination and 4 patients (22%) had a significant disability. There was no relationship between the clinical disability at follow-up examination and the results of initial or final nerve conduction studies. Electromyographic evidence of denervation, however, may indicate that complete clinical recovery will not occur. Segmental demyelination was the primary pathological change found in sural nerve biopsies and there was a significant reduction in the density of myelinated fibres in 2 nerves. It is suggested that a subacute onset of the illness,electromyographic evidence of denervation or gross slowing of conduction, and significant reduction of numbers of myelinated fibres or onion-bulb formation on sural nerve biopsy are factors which may indicate a prolonged course of the illness or incomplete recovery.

After an introductory description of the terminology, the individual experiences of 65 patients with chronic lymphocytic radicular myelo-meningitis after tick bite are reported with reference to the literature. The finding of the cerebrospinal fluid in the lymphoplasmocytic meningitis together with radicular and regional pains, and a one-or two-sided peripheral facial nerve paresis represents the nucleus syndrome of the illness, which usually progresses as meningopolyneuritis. The pathogen, probably a virus, could not yet be isolated. The treatment is purely symptomatical with corticosteroids and antibiotics. Quoad vitam, the prognosis is invariably favourable, residues are frequent.

The characteristics and temporal profiles of cerebrospinal fluid (CSF) and serum immunoglobulin patterns on agarose gel electrophoresis were studied in 47 patients with acute idiopathic polyneuropathy (AIP) and 15 patients with chronic relapsing polyneuropathy (CRP). Nineteen of 47 patients with AIP had transient oligoclonal IgG bands, which disappeared when the neurologic signs subsided. By contrast, 14 of 15 patients with CRP had a "monoclonal" (single) IgG band, which (1) was unchanged on repeated CSF examinations over 18 months, (2) was unaffected by corticosteroid therapy, and (3) did not correlate with the severity or chronicity of the disease. Serum protein patterns and in situ central nervous system IGG synthesis and IgG:albumin index were normal in the CRP patients. The origin of the band and the nature of the putative antigen(s) that the band may be directed against were not identified. Our findings suggest that different immunopathogenic mechanisms may be operating in CRP, compared with AIP. The stable IgG band in CRP may reflect response to a persisting antigenic stimulation and, with further experience, may prove to be of prognostic significance by furnishing early in the illness: (1) a clue to the subsequent course of the disease, and (2) possible guidance on therapeutic decisions.

Clinical assessment, CSF changes, electrophysiologic findings, and nerve biopsy investigations are reported for ten cases of chronic idiopathic polyneuritis. Seven cases developed a progressive, three a relapse course. Motor deficit syndromes predominated, often with proximal weakness. Sensory signs were less frequent and less intense, although exceptions were noted. Elevated CSF total protein and a disproportional increase in IgG developed, which increased with duration of the disease. Nerve conduction velocity was markedly reduced. Nerve biopsies showed cell-mediated demyelination, simultaneous de- and remyelination, considerable alteration of Schwann cells, and long-persisting glycolipid-rich myelin degradation products. Particular features of chronic polyneuritis are delineated. The demyelinating process seems to be "self-perpetuating" and not monophasic as the acute forms. Schwann cells or their surface antigens seem to be targets of the immune response. Chronic polyneuritis responds to treatment with corticosteroids. Long-term treatment in combination with immunosuppressants and plasmapheresis is often required.

Lyme disease is a multisystem disorder resulting from infection by the tick-borne spirochete, Borrelia burgdorferi. Fever, chills, malaise and headaches; a characteristic rash; and subsequent polyarthritis typically herald the onset of this condition. Neurologic involvement may occur with skin and joint manifestations or present alone as meningitis, cranial neuritis, and radiculopathy known as Bannwarth's syndrome. We report the cerebrospinal fluid (CSF) cytomorphologic and immunocytochemical features of four patients who presented with isolated meningitis, cranial neuritis, and painful neuropathy without initial history of specific skin rash or previous tick bite. Initial CSF findings of significant numbers of markedly atypical plasmacytoid mononuclear cells suggested CSF non-Hodgkin's malignant lymphoma. Immunocytochemical studies on CSF specimens, however, revealed polyclonal surface immunoglobulin patterns consistent with an inflammatory reaction. Follow-up clinical history and/or peripheral blood serologic testing for antibody titers with B. burgdorferi antigen confirmed the diagnosis of Lyme disease in all four cases. We conclude that Lyme disease may present as atypical spinal fluid lymphoplasmacytic cellular infiltrates that simulate malignant lymphoma and that appropriate immunocytochemical studies and peripheral blood serologic testing be performed to establish this diagnosis and direct appropriate therapy.

The basic principles, prerequisites, and limitations of the immunoelectrophoresis of the cerebrospinal fluid are discussed. Major emphasis has been placed on the characteristics of normal and pathological immunoelectropherograms of the liquor cerebrospinalis as well as on the results of studies of inflammatory and neuroimmunological diseases. The detection of a barrier profile, the method of determining special qualitative alterations of immunoglobulins of the liquor cerebrospinalis due to neuroimmunological diseases, and additional applications are discussed in detail. The procedure has been critically reviewed because the results obtained are, for the most part, of a general and nonspecific character and the method cannot be standardized adequately and also does not yield sufficient quantitative data. The advantages (differentiated qualitative changes) and disadvantages (technique troubles) are pointed out.

The preliminary data from a study of the cerebrospinal fluid IgG of 76 neurological patients are reported. The radial immunodiffusion method was employed. The absolute and percentage increase of IgG with respect to total proteins in the various diagnostic classes involved in the series was considered. The most significant increases were encountered in M.S., in neuropathies and radiculopathies and in tumor involving the subarachnoid spaces. The high percentage is, however, characteristic of M.S. The method is thus particularly useful in diagnosing M.S. and in differentiating it from other neurological diseases.

Antibodies against Borrelia burgdorferi develop slowly. Low titers can be anamnestic. In order to prove the etiology of manifestations of erythema chronicum migrans disease of the nervous system like meningopolyneuritis Garin-Bujadoux-Bannwarth or progressive borrelia encephalomyelitis we used the ELISA to measure specific IgG antibodies against Ixodes ricinus borrelia per microgram IgG in serum and cerebrospinal fluid. With the mentioned method we were able to demonstrate locally synthesized antibodies in the cerebrospinal fluid. Until the 110th day of illness a difference between serum and CSF in favour of the latter as high as five binary dilution steps could be found. Later on in time the difference decreased to four dilution steps or less.

Aldolase levels were estimated in the cerebrospinal fluid of patients with infectious diseases of the central nervous system. A significant rise was found in bacterial and cryptococcal meningitis but the investigation failed to elucidate the source and clinical significance of the elevated activity.

Investigations on pathophysiological processes in the CSF space due to impairment of the blood-CSF barrier and due to an immune reaction are reported. Barrier disturbances and immune reaction are demonstrated by means of absolute values of CSF protein electrophoresis and by measurement of immunoglobulins. With inflammatory diseases of the CNS, an altered blood-CSF barrier will often be seen at the moment of the first lumbar puncture. Multiple sclerosis, subacute leucoencephalitis and neurosyphilis show signs of a distinct immune reaction together with an increase of the gamma-globulins as well as the immunoglobulin G in the absence or slight presence of a barrier impairment. Non-inflammatory diseases of the CNS have variable barrier disturbances.

Cerebrospinal fluids (CSF) from 66 patients with a variety of neurological disorders were studied for total protein content, absolute amount of albumin, IgA, IgG and IgM, as well as their quotients (fraction to total protein ratio), cell numbers and B cell and T cell levels. In addition, the percentage of B cells and T cells in the blood was determined in 34 patients and serum immunoglobulin levels were estimated in 51 patients. In noninflammatory diseases of the CNS, the percentage of B cells was slightly higher and T cell levels were lower in the CSF in comparison to corresponding blood values. The B cell to T cell ratio in viral meningitis was altered in the CSF. An apparent increase in the T cell level led to a decrease of B cell values. Similar changes were also found in optic neuritis. The percentage of T cells was higher in relapsing multiple sclerosis than in the chronic progressive form. There were less striking changes in the B cell to T cell ratios in the CSF of other inflammatory diseases of the CNS.