CSF CXCL13 is elevated in patients with CIDP and may reflect higher disease activity.

To evaluate B-cell involvement in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), 11 patients with CIDP, 8 patients with Guillain-Barré syndrome and 13 patients with idiopathic normal pressure hydrocephalus (iNPH) were studied. CSF cytokine and chemokine (IL-10, IL-15, TNF-α, TGF-ß1, GM-CSF, BAFF, CXCL10, and CXCL13) levels were measured by ELISA. The CSF CXCL13 level was significantly higher in patients with CIDP than in those with iNPH. The CSF CXCL13 level was significantly higher in CIDP patients with higher annualized relapse rates and higher modified Rankin scale scores. The CSF CXCL13 level is elevated in CIDP, especially in those with higher disease activity.

Motor chronic inflammatory demyelinating polyneuropathy (CIDP) in 17 patients: Clinical characteristics, electrophysiological study, and response to treatment.

Motor chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare and poorly described subtype of CIDP. We aimed to study their clinical and electrophysiological characteristics and response to treatment. From a prospective database of CIDP patients, we included patients with definite or probable CIDP with motor signs and without sensory signs/symptoms at diagnosis. Patients were considered to have pure motor CIDP (PM-CIDP) if sensory conductions were normal or to have motor predominant CIDP (MPred-CIDP) if ≥2 sensory nerve action potential amplitudes were abnormal. Among the 700 patients with CIDP, 17 (2%) were included (PM-CIDP n = 7, MPred-CIDP n = 10); 71% were male, median age at onset was 48 years (range: 13-76 years), 47% had an associated inflammatory or infectious disease or neoplasia. At the more severe disease stage, 94% of patients had upper and lower limb weakness, with distal and proximal weakness in 4 limbs for 56% of them. Three-quarters (75%) responded to intravenous immunoglobulins (IVIg) and four of five patients to corticosteroids including three of three patients with MPred-CIDP. The most frequent conduction abnormalities were conduction blocks (CB, 82%) and F-wave abnormalities (88%). During follow up, 4 of 10 MPred-CIDP patients developed mild sensory symptoms; none with PM-CIDP did so. Patients with PM-CIDP had poorer outcome (median ONLS: 4; range: 22-5) compared to MPred-CIDP (2, range: 0-4; P = .03) at last follow up. This study found a progressive clinical course in the majority of patients with motor CIDP as well as frequent associated diseases, CB, and F-wave abnormalities. Corticosteroids might be considered as a therapeutic option in resistant IVIg patients with MPred-CIDP.

Immune Cell Profiling of the Cerebrospinal Fluid Provides Pathogenetic Insights Into Inflammatory Neuropathies.

Objective: Utilize immune cell profiles in the cerebrospinal fluid (CSF) to advance the understanding and potentially support the diagnosis of inflammatory neuropathies. Methods: We analyzed CSF cell flow cytometry data of patients with definite Guillain-Barré syndrome (GBS, n = 26) and chronic inflammatory demyelinating polyneuropathy (CIDP, n = 32) based on established diagnostic criteria in comparison to controls with relapsing-remitting multiple sclerosis (RRMS, n = 49) and idiopathic intracranial hypertension (IIH, n = 63). Results: Flow cytometry revealed disease-specific changes of CSF cell composition with a significant increase of NKT cells and CD8+ T cells in CIDP, NK cells in GBS, and B cells and plasma cells in MS in comparison to IIH controls. Principal component analysis demonstrated distinct CSF immune cells pattern in inflammatory neuropathies vs. RRMS. Systematic receiver operator curve (ROC) analysis identified NKT cells as the best parameter to distinguish GBS from CIDP. Composite scores combing several of the CSF parameters differentiated inflammatory neuropathies from IIH and GBS from CIDP with high confidence. Applying a novel dimension reduction technique, we observed an intra-disease heterogeneity of inflammatory neuropathies. Conclusion: Inflammatory neuropathies display disease- and subtype-specific alterations of CSF cell composition. The increase of NKT cells and CD8+ T cells in CIDP and NK cells in GBS, suggests a central role of cytotoxic cell types in inflammatory neuropathies varying between acute and chronic subtypes. Composite scores constructed from multi-dimensional CSF parameters establish potential novel diagnostic tools. Intra-disease heterogeneity suggests distinct disease mechanisms in subgroups of inflammatory neuropathies.

Updated cerebrospinal fluid total protein reference values improve chronic inflammatory demyelinating polyneuropathy diagnosis.

INTRODUCTION: Recent literature has concluded that cerebrospinal fluid total protein (CSF-TP) upper reference limits (URL) should be higher than 45 mg/dl and stratified by age. METHODS: Data-driven URLs were applied to the analysis of a cohort of patients with correctly and incorrectly diagnosed chronic inflammatory demyelinating polyneuropathy (CIDP). Descriptive statistics were calculated, and exploratory analyses were used to test the impact of different CSF-TP URLs on sensitivity and specificity of CIDP diagnosis. RESULTS: The adoption of higher and age-dependent CSF-TP URLs reduced the sensitivity of CSF analysis slightly (from 95% to 84%-86%); however, the overall CIDP detection rate was unchanged. Twelve of 36 (33%) false-positive diagnoses occurred with CSF-TP elevation as the sole supportive criteria. By applying updated CSF-TP URLs, the specificity of CSF analysis increased from 39% to 57%-64%. DISCUSSION: Implementation of data-driven CSF-TP URLs improves CIDP diagnostic specificity without compromising sensitivity, thereby lessening CIDP misdiagnosis. Muscle Nerve 60: 180-183, 2019.

IL-8 as a potential biomarker in Guillain-Barre Syndrome.

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.

Polirradiculopatía inflamatoria crónica sensitiva / Chronic inflammatory sensory polyradiculopathy

La polirradiculopatía inflamatoria crónica sensitiva es una entidad definida, frecuentemente subdiagnosticada y potencialmente tratable. Debe ser sospechada en pacientes con ataxia sensitiva, estudios de conducción nerviosa normales y una resonancia magnética que muestre engrosamiento y realce con gadolinio de las raíces lumbosacras. Presentamos el caso de un hombre de 57 años de edad con marcada ataxia sensitiva en pierna izquierda. Al examen físico presentaba fuerza conservada, reflejos osteotendinosos disminuidos, tacto fino y superficial reducidos por debajo de las rodillas; abatiestesia y apalestesia en ambos pies. Los estudios de conducción nerviosa eran normales, los potenciales evocados somatosensitivos tibiales con ausencia de respuesta bilateral. El líquido cefalorraquídeo presentaba hiperproteinorraquia sin células. La resonancia magnética mostró engrosamiento y realce con gadolinio de las raíces lumbosacras. El paciente fue tratado con inmunoglobulina endovenosa (IgEV) a 2 g/kg durante 5 días, con buena respuesta. La evolución clínica, la hiperproteinorraquia, el realce de raíces en la resonancia magnética, la buena respuesta a la inmunoterapia y la exclusión de otras causas de ataxia sensitiva fueron compatibles con el diagnóstico de polirradiculopatía inflamatoria crónica sensitiva. Para el diagnóstico de esta enfermedad se requiere la identificación del compromiso aislado de las raíces sensitivas.

Chronic inflammatory sensory polyradiculopathy is a defined entity, frequently underdiagnosed, and potentially treatable. It must be suspected in patients with sensory ataxia, normal nerve conduction studies, and MRI with thickened lumbosacral nerve roots and gadolinium enhancement. We present the case of a 57-year-old man with marked sensory ataxia on his left leg. Examination showed normal strength, decreased knee and ankle jerks. Light touch and pinprick sensations were reduced below the knees. Vibration and joint position sense were absent at the feet. Nerve conduction studies were normal. Tibial sensory evoked potentials disclosed absent responses bilaterally. CSF was acellular with elevated protein. Lumbosacral magnetic resonance showed thickening of roots, with gadolinium enhancement. The patient was treated with IV-Ig, 2 g/kg, for 5 days with improvement of symptoms. The clinical course, elevated CSF protein, the evidence of root enhancement on the MRI, good response to immunotherapy, and the exclusion of other causes of sensory ataxia, were compatible with the diagnosis of chronic inflammatory sensory polyradiculopathy. To diagnose this disease the identification of isolated involvement of the sensory roots is required.

Chronic inflammatory demyelinating polyradiculoneuropathy: from bench to bedside.

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.

Advances in the diagnosis, pathogenesis and treatment of CIDP.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is the most common chronic autoimmune neuropathy. Despite clinical challenges in diagnosis-owing in part to the existence of disease variants, and different views on how many electrophysiological abnormalities are needed to document demyelination-consensus criteria seem to have been reached for research or clinical practice. Current standard of care involves corticosteroids, intravenous immunoglobulin (IVIg) and/or plasmapheresis, which provide short-term benefits. Maintenance therapy with IVIg can induce sustained remission, increase quality of life and prevent further axonal loss, but caution is needed to avoid overtreatment. Commonly used immunosuppressive drugs offer minimal benefit, necessitating the development of new therapies for treatment-refractory patients. Advances in our understanding of the underlying immunopathology in CIDP have identified new targets for future therapeutic efforts, including T cells, B cells, and transmigration and transduction molecules. New biomarkers and scoring systems represent emerging tools with the potential to predict therapeutic responses and identify patients with active disease for enrollment into clinical trials. This Review highlights the recent advances in diagnosing CIDP, provides an update on the immunopathology including new target antigens, and discusses current treatments, ongoing challenges and future therapeutic directions.

Quantification of cystatin C in cerebrospinal fluid from various neurological disorders and correlation with G73A polymorphism in CST3.

Cystatin C (CC) is a cysteine protease inhibitor abundantly expressed in the central nervous system. Bunina bodies, small eosinophilic intraneuronal inclusions, are stain positive for CC and are the most specific histological hallmark of amyotrophic lateral sclerosis (ALS). In this study, employing a latex turbidimetric immunoassay, levels of CC in cerebrospinal fluid (CSF) were quantified in 130 age-matched individuals with either a neurological disorder [ALS, Alzheimer's disease (AD), Parkinson's disease (PD), tauopathy (TP), multiple system atrophy (MSA), chronic inflammatory demyelinating polyneuropathy (CIDP)] or no known neurological condition (normal control, NC). The CC level in CSF was found to be correlated with the age during the investigation but not the protein concentration. There was no difference in CC levels between NC and ALS or CIDP cases, whereas CC levels were significantly lower in MSA compared with NC. Of the 130 cases, 96 were genotyped, and G/A or A/A polymorphism at +73 within the CST3 gene was found in 28 individuals. The CC level was significantly lower in the combined group of G/A and A/A genotypes compared with G/G. The present data demonstrate that the level of CC in CSF should not be considered as a biomarker of ALS, but there is a correlation between CC levels and the CST3 genotype.

Epstein-Barr virus antibodies in serum and cerebrospinal fluid from multiple sclerosis, chronic inflammatory demyelinating polyradiculoneuropathy and amyotrophic lateral sclerosis.

Elevated anti-Epstein-Barr virus (EBV) antibody levels are present in serum of Multiple sclerosis (MS) patients but literature lacks of studies comparing anti-EBV antibody levels between MS and other neurological diseases. We evaluate anti-VCA IgG and IgM, anti-EBNA1 IgG, anti-Cytomegalovirus IgG and IgM titres in serum and cerebrospinal fluid (CSF) of 267 MS, 50 Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) and 88 Amyotrophic Lateral Sclerosis (ALS) patients. We found increased titres of anti-EBV-IgG in serum and CSF of MS subjects as compared to CIDP and ALS patients thus providing additional evidence for a possible involvement of EBV in MS.

The expression pattern of inflammatory mediators in cerebrospinal fluid differentiates Guillain-Barré syndrome from chronic inflammatory demyelinating polyneuropathy.

INTRODUCTION: Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) share histopathological features but display different disease courses; we measured the concentration of 50 inflammatory mediators in the cerebrospinal fluid (CSF) of patients with either of these diseases. PATIENTS AND METHODS: CSF samples were collected during a diagnostic lumbar puncture and stored at -30 degrees C. We analyzed the CSF of nine subjects with GBS; eight with CIDP; eight with diabetic polyneuropathy (DP) and seven with headache (controls). Fifty inflammatory mediators were simultaneously measured with a multiplex bead-based ELISA on a Suspension Array System. After Bonferroni's correction for repeated measures, non-parametric variance and post hoc test were calculated. RESULTS: Thirty-two inflammatory mediators were expressed. The median concentration of IL-6, IL-9, IL-15, IL-18, CCL4, CXCL1, LIF, MIF, PDGFbb, IFN-gamma2, IL-2ra, IL-12(p40), IL-16, SCGF-b, TRAIL, FGF, G-CSF, GM-CSF, and M-CSF was not different among groups (variance: n.s.). The median concentration of CCL2, CCL7, CCL27, CXCL9, CXCL10, CXCL12, ICAM-1, VCAM1 and VEGF was higher in CIDP and GBS compared with controls (p<0.002). The median concentration of IL-8 and IL-1ra was higher in GBS than CIDP or DP or controls, whereas stem cell factor (SCF) and hepatocyte growth factor (HGF) were higher in CIDP than GBS or DP or controls (p<0.002). DISCUSSION: Mediators of the recruitment and activation of lymphocytes and monocytes are expressed in the CSF of CIDP and GBS. IL-8 and IL-1ra are characteristic of GBS, whereas growth factors (SCF, HGF) of CIDP are possibly related to chronicity or to the survival/repair processes of neurons.

Elevation of Gas6 protein concentration in cerebrospinal fluid of patients with chronic inflammatory demyelinating polyneuropathy (CIDP).

INTRODUCTION: Gas6 enhances survival of Schwann cells and neurons in vitro and participates in autoimmunity in animal models. Since its concentration in human cerebrospinal fluid (CSF) is unknown, we measured it in samples from patients with non-inflammatory/non-autoimmune neurological diseases (NINAD) and autoimmune polyneuropathies. MATERIALS AND METHODS: Samples collected after informed consent during diagnostic lumbar puncture in the period 1999-2006 were stored at -30 degrees C. We considered subjects with NINAD (stroke, ALS, headache, psychiatric conditions simulating neurological diseases, otologic dizziness) or with Guillain-Barré syndrome (GBS) or CIDP. CSF and plasma total protein and age were obtained from clinical records. Gas6 was measured with an ELISA developed and validated in our laboratory (inter-, intra-assay CVs <10%, recovery 96%). Variance, Tukey's post-hoc test, regression were calculated with a statistical software (Statsoft). RESULTS: Mean Gas6 concentration in patients with NINAD was 6.5+/-2.4 ng/ml, 7.2+/-2.6 ng/ml in GBS and significantly higher (11.5+/-1.7 ng/ml) in CIDP than in the other conditions (post-hoc, p<0.005). It was not related to age, CSF total proteins or to CSF/plasma ratio of total proteins (regression, p>0.1). CONCLUSIONS: Gas6 is detectable in CSF and may be involved in chronic autoimmune demyelination or myelin repair.

Idiopathic chronic inflammatory demyelinating polyneuropathy: an epidemiological study in Italy.

AIM: The clinical and epidemiological characteristics of chronic inflammatory demyelinating polyneuropathy (CIDP) in an Italian population were assessed. SUBJECTS AND METHODS: All subjects with a diagnosis of demyelinating neuropathy after 1990 in Piemonte and Valle d'Aosta (4,334,225 inhabitants) were considered. The diagnosis of CIDP was based on the research criteria of the American Academy of Neurology. 165 of 294 patients met the diagnostic criteria. RESULTS: The crude prevalence rate was 3.58/100,000 population (95% CI 3.02 to 4.20). At the prevalence day, 76 (49.0%) cases had definite, 67 (43.2%) probable and 12 (7.7%) possible CIDP; disability was mild in 105 (67.7%) cases, moderate in 32 (20.6%) and severe in 18 (11.6%). The course was remitting-relapsing in 40 cases (25.8%), chronic progressive in 96 (61.9%) and monophasic in 19 (12.3%). Considering the 95 patients whose disorder presented in the period 1995-2001, the mean annual crude incidence rate was 0.36/100,000 population (95% CI 0.29 to 0.44), with a male to female ratio of 2.3:1. 14 cases were affected by diabetes mellitus. In multivariate analysis, factors related to severe disability at the prevalence day were: age >60 years; failure of immunomodulating therapies at the time of diagnosis; worse disability at nadir; and chronic course. CONCLUSION: Incidence and prevalence rates of CIDP in Italy were higher than those observed in most previous studies. At the prevalence day, more than 80% of cases had a mild or moderate disability, indicating either a good response to immunomodulating therapy or a tendency of CIDP to have a mild course in most cases.

[Biochemical features of chronic inflammatory demyelinating polyradiculoneuropathy]. / Les limites biologiques du concept de polyradiculonévrite chronique.

Although there are no specific biological markers of chronic inflammatory demyelinating polyneuropathies (CIDP), biological investigations have played an important role in determining the limits of the concept of CIDP. This is best exemplified by the individualisation of demyelinating neuropathies associated with IgM monoclonal proteins reacting with glycolipids. The signification of CIDP associated with diabetes mellitus, monoclonal IgG or IgA, or mutations of myelin proteins has recently been discussed as they may have implications in our understanding of the pathophysiology of CIDP and raise the question of knowing whether they confer to CIDP a particular clinical presentation or evolution.

Dendritic cells in the cerebrospinal fluid and peripheral nerves in Guillain-Barré syndrome and chronic inflammatory demyelinating polyradiculoneuropathy.

The role of antigen-presenting cells (APC) involved in induction of T and B cell mediated autoaggressive immunity in Guillain-Barre syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is poorly understood. We studied the numbers and phenotype of dendritic cells (DC) in blood and cerebrospinal fluid (CSF) over the course of GBS and CIDP before and after immunomodulatory treatment. Four out of seven GBS patients examined prior to treatment with high-dose intravenous immunoglobulins (IvIg) had elevated numbers of CD123(+) plasmacytoid DC in the CSF, while both GBS and CIDP patients examined prior to treatment had elevated numbers of CD11c(+) myeloid DC in the CSF, as compared to patients with noninflammatory neurological diseases (OND). The percentages of blood DC expressing the cell surface marker CD1a, co-stimulatory molecules CD80 and CD86, adhesion molecule CD54, and chemokine receptors CCR1, CCR2, CCR5, and CXCR4 were not affected in GBS or CIDP. The immunohistochemistry of sural nerve biopsies revealed CD11c(+)CD83(-)CD14(-)CD16(-) immature myeloid DC at low numbers, mostly in the perineurium, without difference between CIDP patients and controls. In contrast, the numbers of CD11c(+)CD14(+)/CD16(+) macrophages were higher within the endoneurium in CIDP patients compared with the controls. The recruitment of DC to CSF in GBS and CIDP may be important in capturing antigens released from inflamed spinal nerve roots into CSF and in transferring these antigens from CSF to local lymph nodes, where naive T and B cells may be activated.

Th1 shift in CIDP versus Th2 shift in vasculitic neuropathy in CSF.

To investigate the intra- and extracellular levels of various cytokines and chemokines in CSF in chronic inflammatory demyelinating polyneuropathy (CIDP) and vasculitic neuropathy (VN), 16 cytokines, IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 (p70), IL-13, IL-17, IFN-gamma, TNF-alpha, G-CSF, MCP-1 and MIP-1beta, were measured in CSF supernatant by a multiplexed fluorescent bead-based immunoassay and intracellular production of IFN-gamma and IL-4 in CSF CD4+ T cells were simultaneously measured by flow cytometry in 14 patients with CIDP, 8 patients with VN and 25 patients with other noninflammatory neurologic diseases (OND). In the CSF supernatant, a significant increase of IL-17, IL-8 and IL-6, and a significant decrease of IL-4, IL-5 and IL-7 levels were detected in pretreated CIDP as compared with OND. A significant increase of IL-6, IL-8 and IL-10 levels was found in pretreated VN. Both IL-17 and IL-8 levels correlated strongly with CSF protein levels in CIDP, although the correlation of IL-6 levels was weak. In CSF CD4+ T cells, IFN-gamma+ IL-4- cell percentages were markedly elevated in CIDP compared with OND, but not in VN, resulting in a significant increase of intracellular IFN-gamma/IL-4 ratio in CIDP, even in the absence of CSF pleocytosis. The nonresponders to intravenous immunoglobulins (IVIGs) showed a significantly lower IFN-gamma- IL-4+ CD4+ T cell percentage, and tended to have a higher intracellular IFN-gamma/IL-4 ratio than the responders in CSF. Marked upregulation of Th1 cytokine, IL-17, and downregulation of Th2 cytokines, together with infiltration of IFN-gamma-producing CD4+ T cells are useful markers for CIDP, while several Th2 cytokines are upregulated in VN in CSF.

Optic nerve sheath fenestration for intracranial hypertension associated with chronic inflammatory demyelinating polyneuropathy.

The authors report a case of papilledema in a 61-year-old woman with chronic demyelinating polyneuropathy. The cerebrospinal fluid protein level was elevated (2.68 to 4.51 g/L), as was the cerebro-spinal fluid opening pressure (27 to 40 cm H2O). A unilateral optic nerve sheath fenestration proved to be effective in preserving vision, and the papilledema resolved completely.

Research criteria for defining patients with CIDP.

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is one of several chronic acquired demyelinating neuropathies that are considered to be autoimmune diseases. The prevalence of these illnesses may be underestimated because of limitations in clinical, serologic, and electrophysiologic diagnostic criteria. An Ad Hoc Subcommittee of the American Academy of Neurology (AAN) proposed a set of diagnostic criteria for CIDP to be used for research purposes, and several other criteria followed. Of these, the AAN electrophysiologic criteria are the most restrictive and fit only a subset of patients with CIDP. Other criteria, including the Inflammatory Neuropathy Cause and Treatment (INCAT) clinical and electrophysiologic criteria and the Nicolas or Thaisetthawatkul electrophysiologic criteria, are more sensitive and can therefore identify a broader range of patients with CIDP for clinical trials. Regardless of which criteria are chosen for use in clinical trials, patients who fall outside of these criteria may also have CIDP and may benefit from treatment. Unfortunately, because of the lack of clarity with regard to diagnostic criteria for CIDP, many patients remain untreated. In addition, certain CIDP variants may also respond to treatment. These include sensory CIDP, multifocal motor neuropathy (MMN) with or without conduction block, multifocal acquired demyelinating sensory and motor (MADSAM) neuropathy, distal acquired demyelinating sensory (DADS) neuropathy, and multifocal acquired sensory and motor (MASAM) neuropathy. Therefore, although patients may not meet the diagnostic criteria for inclusion in clinical trials of CIDP, they may still benefit from current and future treatments used in CIDP.

Phenotypic and functional analysis of T cells homing into the CSF of subjects with inflammatory diseases of the CNS.

The recruitment of lymphocytes across the blood brain barrier (BBB) is mediated by adhesion molecules and chemokines. The expression of activation markers and of chemokine receptors on T cells homing to the nervous system (NS) may help define their functional state. In the cerebrospinal fluid (CSF) of subjects with inflammatory neurological diseases (IND), including multiple sclerosis, we observed an increased number of T cells coexpressing CXCR3 and CCR5 as well as T cells with a CD45RO+ CCR7+ CD27+ memory phenotype. A subset of CCR7+ T cells coexpressed CXCR3 and CCR5. We also detected an increased number of interferon-gamma-producing T cells in the CSF compared with peripheral blood, mostly but not exclusively in the CD45RO+ CCR7- CD27- compartment. T helper 1 (Th1) clones, established from the CSF of individuals with IND and from a healthy subject, similarly migrated to CXCL10, CXCL12, and CCL5. CXCL10, CXCL12, and CCL19 were increased in the CSF of individuals with neuroinflammation. These findings suggest that CSF is enriched in Th1-polarized memory T cells capable of differentiating into effector cells upon antigen encounter. These cells are recruited into the CSF by inducible chemokines. Thus, CSF represents a transitional station for T cells trafficking to and from the NS.

Cystatin C and cathepsin B in CSF from patients with inflammatory neurologic diseases.

BACKGROUND: In CSF, proteolytic enzymes are believed to have crucial roles in the initiation and progression of inflammatory neurologic diseases (IND). Cystatin C, a major cysteine protease inhibitor in CSF, is tightly bound to cathepsin B and H. OBJECTIVE: To determine if cystatin C is involved in the disease process of IND, the authors measured the cystatin C concentration by ELISA method and cathepsin B and H activities in the CSF of patients with acute IND. METHODS: Cystatin C concentration and cathepsin B and H activities were measured in CSF samples taken from patients during the acute phase of their disease. Subjects studied were 8 patients with Guillain-Barré syndrome (GBS), 5 with chronic inflammatory demyelinating polyneuropathy (CIDP), 12 with MS, 16 with aseptic meningitis, 15 with neurodegenerative diseases as disease controls, and 35 healthy controls. RESULTS: A significant decrease in CSF cystatin C level was seen in the patients with GBS, CIDP, and MS compared to the control subjects. High cathepsin B activity, but not cathepsin H activity, was also observed in the patients with GBS, CIDP, and MS. CONCLUSION: Cystatin C levels in CSF measured by ELISA may help the physician recognize GBS, CIDP, and MS. Decreased levels of cystatin C may be related to the high levels of cathepsin B activity seen in the CSF of patients with GBS, CIDP, and MS.