Kappa free light chains is a valid tool in the diagnostics of MS: A large multicenter study.

OBJECTIVE: To validate kappa free light chain (KFLC) and lambda free light chain (LFLC) indices as a diagnostic biomarker in multiple sclerosis (MS). METHODS: We performed a multicenter study including 745 patients from 18 centers (219 controls and 526 clinically isolated syndrome (CIS)/MS patients) with a known oligoclonal IgG band (OCB) status. KFLC and LFLC were measured in paired cerebrospinal fluid (CSF) and serum samples. Gaussian mixture modeling was used to define a cut-off for KFLC and LFLC indexes. RESULTS: The cut-off for the KFLC index was 6.6 (95% confidence interval (CI) = 5.2-138.1). The cut-off for the LFLC index was 6.9 (95% CI = 4.5-22.2). For CIS/MS patients, sensitivity of the KFLC index (0.88; 95% CI = 0.85-0.90) was higher than OCB (0.82; 95%CI = 0.79-0.85; p < 0.001), but specificity (0.83; 95% CI = 0.78-0.88) was lower (OCB = 0.92; 95% CI = 0.89-0.96; p < 0.001). Both sensitivity and specificity for the LFLC index were lower than OCB. CONCLUSION: Compared with OCB, the KFLC index is more sensitive but less specific for diagnosing CIS/MS. Lacking an elevated KFLC index is more powerful for excluding MS compared with OCB but the latter is more important for ruling in a diagnosis of CIS/MS.

Cladribine in myasthenia gravis: a pilot open-label study.

BACKGROUND AND PURPOSE: The aim of this study was to assess the effectiveness of cladribine treatments in a population of patients with refractory myasthenia gravis (MG). METHODS: In a prospective open-label study of cladribine in refractory MG, 13 patients received cladribine at baseline with repetitive cycles driven by clinical response. A Myasthenia Gravis Composite (MGC) score was obtained and a standard dose of steroids was administered. RESULTS: A total of 11 patients achieved significant clinical improvement in MGC score during their therapy. The mean MGC score declined from 15.1 to 6.3 points within 4 months of observation. The dosage of prednisolone declined from 9.5 to 1.9 mg. None of the patients required intravenous immunoglobulin or plasma exchange treatments and no adverse events occurred in the study period. CONCLUSION: Cladribine seems to be a safe and effective emergency therapy in a population of patients with refractory MG.

Convulsive status epilepticus management in adults and children: Report of the Working Group of the Polish Society of Epileptology.

INTRODUCTION: The Working Group was established at the initiative of the General Board of the Polish Society of Epileptology (PSE) to develop an expert position on the treatment of convulsive status epilepticus (SE) in adults and children in Poland. Generalized convulsive SE is the most common form and also represents the greatest threat to life, highlighting the importance of the choice of appropriate therapeutic treatment. AIM OF GUIDELINE: We present the therapeutic options separately for treatment during the early preclinical (>5-30min), established (30-60min), and refractory (>60min) SE phases. This division is based on time and response to AEDs, and indicates a practical approach based on pathophysiological data. RESULTS: Benzodiazepines (BZD) are the first-line drugs. In cases of ineffective first-line treatment and persistence of the seizure, the use of second-line treatment: phenytoin, valproic acid or phenobarbital is required. SE that persists after the administration of benzodiazepines and phenytoin or another second-line AED at appropriate doses is defined as refractory and drug resistant and requires treatment in the intensive care unit (ICU). EEG monitoring is essential during therapy at this stage. Anesthesia is typically continued for an initial period of 24h followed by a slow reversal and is re-established if seizures recur. Anesthesia is usually administered either to the level of the "burst suppression pattern" or to obtain the "EEG suppression" pattern. CONCLUSIONS: Experts agree that close and early cooperation with a neurologist and anesthetist aiming to reduce the risk of pharmacoresistant cases is an extremely important factor in the treatment of patients with SE. This report has educational, practical and organizational aspects, outlining a standard plan for SE management in Poland that will improve therapeutic efficacy.

Processes of plasma protein N-homocysteinylation in multiple sclerosis.

BACKGROUND: Homocysteine thiolactone (HTL) is a cyclic thioester of homocysteine (Hcy) contributing to the toxicity of this amino acid. HTL spontaneously reacts with protein lysine residues leading to altered properties of target proteins and induction of immune response. HTL is hydrolyzed to Hcy by plasma enzyme, paraoxonase 1 (PON1). Although both Hcy and PON1 may be involved in the pathogenesis of multiple sclerosis (MS), protein modification by HTL in this disease has not been studied so far. Purpose/Aim: The aim of this study was to assess the level of Hcy, HTL and autoantibodies against N-homocysteinylated proteins as well as PON1 activity in patients with MS. METHODS: The studies were performed in 61 MS patients with relapsing-remitting (RR group, n = 25) and secondary-progressive type of MS (SP group, n = 36), and in healthy people (C - control group, n = 44). RESULTS: Homocysteine level was significantly higher in MS patients comparing to control group (C vs. RR p < 0.01; C vs. SP p < 0.05). The level of HTL tended to be higher in RR-MS in comparison to control group, but it did not reach the level of significance. The level of antibodies against N-homocysteinylated proteins did not differ significantly between studied groups. PON1 activity was significantly lower in SP type of MS (SP vs. C p < 0.05; SP vs. RR p < 0.05). CONCLUSIONS: Although plasma Hcy concentration is higher in MS patients and PON1 activity is reduced in the SP form, MS is associated with minor or no changes in protein-attached HTL and anti-homocysteinylated protein immune response.

Traumatic bilateral dissection of cervical internal carotid artery in the wake of a car accident: A case report.

BACKGROUND: Bilateral carotid artery dissection secondary to severe trauma is rare and can be potentially life -threatening if not diagnosed and treated properly. CASE PRESENTATION: We report a 29-year-old female who was admitted to the emergency department after a car accident. The patient was conscious at the time of admission and presented with an initial Glasgow Coma Scale (GCS) of 15 presenting normal vital signs. The patient developed motor dysphasia with right upper limb paresis a few hours after the admission. Magnetic resonance imaging (MRI) revealed a bilateral cervical internal carotid artery (ICA) occlusion in addition to left frontal lobe infarct in a subacute phase. Medical management was successful and the patient was discharged from the hospital two weeks after the admission. DISCUSSION: Noninvasive vascular imagining modalities are merging as the gold standard in the early detection of carotid artery dissection (CAD). Typical pathognomonic findings on MRI include double lumen and intimal flap. The management with systemic anticoagulation or antiplatelet therapy is aimed to prevent the development of ischemic stroke. In case of medical therapy being ineffective or in case of complication or any disorders suffered by a patient, endovascular treatment is performed. CONCLUSION: With early detection and proper management, traumatic dissection of cervical carotid artery can have a benign outcome. As for the current patient, medical treatment with anticoagulation was sufficient and surgical management was therefore not required. Improvement in the patients' speech was observed; nevertheless the continuation of speech therapy was indicated.

Cerebrospinal fluid biomarkers of ß-amyloid metabolism and neuronal damage in epileptic seizures.

BACKGROUND AND PURPOSE: The main objectives of this study were to investigate if epileptic seizures have effects on brain metabolism of ß-amyloid (Aß), as reflected by cerebrospinal fluid (CSF) levels of different isoforms of Aß peptides and soluble amyloid precursor protein (APP), and neuronal degeneration, as reflected by CSF biomarker signs of acute neuronal injury. METHODS: Forty-five patients were included, 21 of whom had single generalized tonic-clonic seizures sGTCS), 11 had repetitive GTCS, 7 had repetitive partial seizures (rPS), 6 had single partial seizure (sPS) and 4 fulfilled the criterion for non-convulsive status epilepticus (nSE). CSF was analyzed for Aßx-38, Aßx-40, Aßx-42, Aß1-42, soluble APP fragments (sAPP-α/ß), total-tau (T-tau) and phosphorylated tau (P-tau), as well as heart-type fatty acid binding protein (H-FABP). RESULTS: Patients with seizures had decreased levels of T-tau (P = 0.0016) and P-tau (P = 0.0028) compared with controls, but no differences in H-FABP (P = 0.67). There were no overall differences in Aß or sAPP peptides between seizure patients and controls. In patients with rPS, the levels of Aßx-38 and Aßx-40 were elevated compared with nSE (P < 0.01), sPS (P < 0.05) and controls (P < 0.05), and Aßx-42 was elevated in rPS relative to nSE (P < 0.05). CONCLUSIONS: The findings of this study argue against acute neuronal injury following medically treated seizures but suggest that seizures may reduce CSF levels of tau. Although seizures generally did not affect CSF levels of Aß or sAPP peptides, our findings suggest that different types of seizures may have different effects on APP metabolism.

Nuclear mapping in parathyroidectomy: the impact on operative time.

BACKGROUND: Precise intraoperative localization and identification of hyperactive parathyroid tissue remains one of the most challenging tasks for surgeons performing parathyroidectomies. Among a few adjuvant methods tested recently, a novel technique called nuclear mapping may become a real breakthrough in parathyroid surgery. It is based on intraoperative detection of radioactivity after previous intravenous administration of 99mTc Sestamibi, which is accumulated in hyperactive parathyroid tissue. The purpose of this study was to assess the impact of nuclear mapping on operative time in parathyroidectomy. METHODS: The study was conducted as a retrospective univariable and multivariable analysis of clinical factors potentially influencing the operative time in a group of 27 patients undergoing parathyroidectomy. RESULTS: Univariable analysis revealed that nuclear mapping was associated with significant reduction in operative time (79.4 +/- 62.2 min vs. 135.8 +/- 49.2 min; p = 0.0186); whereas, bilateral neck exploration, partial sternotomy and reoperative neck prolonged the procedure by mean 70.7 +/- 12.9 min (p = 0.0035); 100,9 +/- 50.36 min (p = 0.0154) and 73.3 +/- 22.8 min (p = 0.0081), respectively. Multivariable analysis using a multiple regression model identified nuclear mapping, sternotomy and reoperative neck as independent variables significantly influencing the duration of parathyroidectomy. CONCLUSIONS: Nuclear mapping is an efficient intraoperative adjuvant technique facilitating localization of hyperactive parathyroid tissues in vivo and instantly confirming their identity ex vivo. It guides the surgeon throughout the parathyroidectomy and is associated with significant reduction in operative time.

Urinary neopterin and nitric oxide metabolites as markers of interferon beta-1a activity in primary progressive multiple sclerosis.

BACKGROUND: Interferon beta has not been demonstrated to be effective in exploratory phase 2 clinical trials in primary progressive multiple sclerosis. However, using more sensitive indicators of a treatment response, such as biomarkers, might help to identify sub-groups of patients who may benefit from therapy. OBJECTIVE: To assess the utility of measuring urinary neopterin and nitric oxide metabolite excretion for monitoring interferon beta-1a (IFNbeta-1a) treatment in patients with primary progressive multiple sclerosis. METHODS: Fifty patients from a phase II trial of IFNbeta-1a (Placebo n = 20; Avonex 1 x 30 microg/week (IFN-30), n = 15; Avonex 1 x 60 microg/week (IFN-60), n = 15), were enrolled. Patients were assessed using the Expanded Disability Status Scale. Urine samples were collected on each visit, 3 months apart, for a period of 24 months. Nitric oxide metabolites, nitrite/nitrate (NOx), were measured by colorimetric assay and neopterin and creatinine (Cr) were assayed using a high-performance liquid chromatography technique. NOx/creatinine ratio (NOxCR) and urinary neopterin/creatinine ratio (UNCR) quotients were calculated. RESULTS: There was no significant difference between pre-dose, baseline levels of UNCR or NOxCR between the study groups. On the intention-to-treat analysis, there was a significant difference in UNCR levels between the placebo compared with IFN-30 (p = 0.03) or IFN-60 (p = 0.002) groups. The IFN-30 and IFN-60 groups did not differ. Within IFNbeta-1a-treated patients with primary progressive multiple sclerosis, median UNCR values were significantly higher in clinically stable (no Expanded Disability Status Scale change) compared with progressive patients (p = 0.002). IFNbeta-1a treatment did not significantly influence NOx excretion in patients with primary progressive multiple sclerosis. CONCLUSIONS: Urinary neopterin is a potential biomarker to monitor the in vivo effects of IFNbeta-1a in primary progressive multiple sclerosis and other multiple sclerosis sub-types.

Pain incidence in cervical dystonia is determined by the disease phenotype.

BACKGROUND: Cervical dystonia (CD) is a movement disorder caused by prolonged contractions of the head and neck muscles resulting in abnormal postures and repetitive movements. Depending on the direction of the head and neck deviation, CD phenotypes are divided into torti-, latero-, antero-, and retro- impairments assessed in commonly used TWSTRS classification, or -caput and -collis according to the novel Col-Cap concept. Cervical pain, which pathophysiology has not been fully elucidated, affects more than 60% of CD patients. To date, none of the studies have investigated the risk of pain associated with the particular disease phenotype. METHODS: In this observational study data collection was based on the survey completion by the participants, analysis of the medical records, and physical examination with the use of proper scales (TWSTRS, Col-Cap, Tsui). Extended pain profile questionnaire included detailed questions about pain localization, character, and intensity. RESULTS: We examined 60 patients suffered from CD; 66,7% of them reported cervical pain. Latero- as the only TWSTRS phenotype was associated with increased risk of pain occurrence (OR = 3,95; p < 0,05). Interestingly, each of two Col-Cap phenotypes correlated with cervical pain: -caput positively (OR = 3,78; p < 0,05) and -collis negatively (OR = 0,29; p < 0,05). CONCLUSIONS: The risk of dystonic pain was highly differentiated within the particular CD phenotypes. The enhanced risk of cervical pain was observed in latero- (TWSTRS) and -caput (Col-Cap) phenotypes; conversely, -collis type (Col-Cap) was characterized by the lowest risk of cervical pain.

Increased urinary excretion of nitric oxide metabolites in longitudinally monitored migraine patients.

This study evaluated a relationship between nitric oxide (NO) and migraine attacks in order to gain insight into migraine pathomechanism. The study groups consisted of 12 migraineurs and eight controls. All subjects collected morning urine samples for 40 consecutive days. Urinary NO metabolites, nitrite/nitrate (NO(x)) levels were measured with the vanadium-based assay, whilst creatinine (Cr) and neopterin were determined with high-performance liquid chromatography. The mean urinary NO(x)/Cr ratio and number of NO(x) peaks was significantly greater in the migraine group compared with controls (P = 0.01 and P = 0.007, respectively). In the second approach, high NO(x) values were re-assessed in relation to raised neopterin, a marker of systemic infection or inflammation, and were excluded. The excretion of NO(x) persisted being pulsatile, and migraineurs had more peaks compared with controls (P = 0.01). In seven patients, NO(x) peaks coincided with headache days. This was more frequent than expected by random association in four patients (Monte-Carlo simulation; odds ratios: 2.16-7.77; no overlap of 95% CI). In four patients, NO(x) peaks preceded or followed headache days. Although there is a difference in the pattern of urinary NO(x) excretion between control and migraine populations, the variable temporal association of NO(x) peaks and headaches suggests a complex role of NO in this condition.

Axonal pathology in subarachnoid and intracerebral hemorrhage.

Electrically active axons degenerate in the presence of nitric oxide (NO) in vitro. High CSF NO concentrations have been observed in patients with hemorrhagic brain injury such as subarachnoid hemorrhage (SAH) and intracerebral hemorrhage (ICH). This study investigated the evidence for axonal injury in SAH and ICH and related this to CSF NO levels. In this study, neurofilament phosphoforms (NfH(SMI34), NfH(SMI35), NfH(SMI38), NfH(SMI310)), surrogate markers for axonal injury, and NO metabolites (nitrate, nitrite = NOx) were measured by ELISA in cerebrospinal fluid (CSF) from patients with SAH and ICH and from a group of controls. Injury severity was classified using the Glasgow Coma Scale, and survival was used as the outcome measure. Compared to the control group, a higher proportion of patients with SAH and ICH had elevated NfH(SMI34) levels from day 0 to day 6 (p < 0.001), elevated NfH(SMI35) levels from day 1 to 6 (p < 0.001), and elevated NfH(SMI310) levels at day 0, 1, 4, and 6 (p < 0.001). The NOx levels were higher in the SAH and ICH patients than in the controls (p < 0.05) and distinguished the non-survivors from the survivors (p < 0.05). No direct correlation was found for NOx with any of the NfH phosphoforms. This study provides evidence for primary and secondary axonal injury in patients with SAH and ICH, with non-survivors also having higher NOx levels. CSF NfH phosphoforms might emerge as a putative surrogate marker for monitoring the development for secondary axonal degeneration in neurocritical care and guiding targeted neuroprotective strategies.

The effects of citicoline and/or MK-801 on survival, neurological and behavioral outcome of mice exposed to transient hyperglycemia and oligemic hypoxia.

UNLABELLED: The effects of citicoline and/or low dose of MK-801 (sufficient to prevent the development of seizures) on survival, neurological and behavioral recovery following transient hyperglycemic-oligemic-hypoxic insult have been evaluated in mice. Neurological recovery was assessed semi-quantitatively on the third and the 10th day after the insult, and behavioral tests evaluating spontaneous locomotor activity, motor coordination and spontaneous alternation performance were performed on day 10. Neither drug given alone did influence survival rate, but the combination of MK-801 and higher citicoline dose decreased mortality on day 10. Behavioral performance was markedly compromised by the insult. Citicoline, but not MK-801, slightly but significantly improved behavioral outcome in all three tests. CONCLUSION: when brain ischemic insult is complicated with acute hyperglycemia, post-treatment with citicoline combined with MK-801 in low anti-convulsive dose improves survival and neurological recovery, and citicoline but not MK-801 enhances behavioral recovery.

Serum and urine nitrate and nitrite are not reliable indicators of intrathecal nitric oxide production in acute brain injury.

This study examined the correlation between nitric oxide (NO) metabolites in the three major body fluid compartments and assessed performance of newly described vanadium-based assay for simultaneous detection of nitrite and nitrate (NO(x)) in human samples. Vanadium reduces nitrate to nitrite, which can be measured after a colorimetric reaction with Griess reagents. Cisternal cerebro spinal fluid (CSF), serum and urine samples from 10 patients with acute brain injury (ABI) were compared to control subjects. Significantly higher CSF NO(x) levels were found in brain injury patients compared to control patients (19.7+/-13.7 vs. 6.5+/-2.3 microM; p=0.01), which persisted for 10-day period of observation. The serum and urine levels of NO(x) on admission were not statistically different (42.8+/-28.2 microM; 584.1+/-337.8 micromol/g Cr, respectively) from controls (36.8+/-14.8 microM; 819.7+/-356.0 micromol/g Cr), but tended to decrease during the disease course reaching the lowest level on day 6 (serum: 19.3+/-8.4 microM, urine: 300.4+/-111.9 micromol/g Cr). CSF levels of NO(x) correlated moderately with those in serum (p=0.001, R=0.5). Serum NO(x) concentrations correlated weakly with urine levels (p=0.04, R=0.3). There was no significant correlation between CSF NO(x) and urine NO(x) levels. In conclusion, patients suffering brain injury had increased NO(x) concentrations in CSF, which remained independent from other body fluid compartments. Serum and urinary NO(x) levels cannot be used as a reliable index to assess intrathecal NO production.

2-deoxyglucose enhances epileptic tolerance evoked by transient incomplete brain ischemia in mice.

The aim of the study was to assess the influence of chronic treatment with a non-metabolisable glucose analogue, 2-deoxyglucose (2-DG) at a 150 mg/kg dose on long-term epileptic tolerance (ET) evoked by 30 min bilateral carotid artery clamping (BCCA) in mice. The effects of protein synthesis inhibition with cycloheximide (CHX), given in three daily doses of 2.5 mg/kg starting either 1 day before (peri-insult regimen) or 1 day after the priming insult (post-insult regimen), on ET development was also studied. Seizures were induced 14 days after BCCA with 3.5 mg/kg of bicuculline; this dose (CD97) evokes convulsions in 97% of normal untreated mice. BCCA resulted in decreased mortality, prolonged latency to the onset of generalised convulsions and decreased overall seizure score. CHX given in the post-insult regimen did not influence, while the peri-insult regimen abolished, all signs of BCCA-evoked ET. 2-DG treatment of sham-operated animals resulted in a moderate but significant decrease in mortality rate and a tendency toward a lower seizure score. BCCA combined with 2-DG treatment resulted in a marked decrease in mortality rate, as well as reduction in all indicators of seizure susceptibility. CHX abolished the antiepileptic effects of BCCA alone, as well as BCCA combined with 2-DG, while it did not influence the 2-DG-related decrease in mortality. We conclude that the development of BCCA-induced epileptic tolerance, as well as unmasking antiepileptic effects of 2-DG by BCCA, is dependent on protein synthesis.

The effect of CGP-40116 on pilocarpine evoked seizures in mice exposed to transient episode of brain ischemia.

The objective of the study was to examine the role of N-methyl-D-aspartate (NMDA) receptors in the modulation of a brain tolerance after a transient cerebral ischemia. Adult mice were exposed for 30 min to bilateral clamping of common carotid arteries (BCCA) under anaesthesia. The competitive NMDA antagonist CGP-40116 was administered intraperitoneally (i.p.) in two experimental paradigms, (a) acute treatment: twice, 4.0 mg/kg; 1.5 h before the clamping of vessels and 6 h after re-circulation and (b) chronic treatment in a dose of 1.0 mg/kg; started 24 h after re-circulation and continued once daily for 13 days with the last injection 24 h before the induction of convulsions. Seizures were evoked with pilocarpine (400 mg/kg, i.p.) 14 days after BCCA. The preliminary study showed that BCCA induced protection against pilocarpine toxicity. The acute treatment with CGP-40116 partially diminished the anticonvulsant phenomenon. In contrast, the chronic treatment with the drug led to a marked potentiation of the effect. The whole brain gamma-aminobutyric acid (GABA) analysis performed 14 days after BCCA showed a moderate increase in vehicle-treated mice and a significant elevation after chronic treatment with CGP-40116. It can be concluded that NMDA antagonists may exert the opposite effects on the brain tolerance against pilocarpine toxicity after BCCA. The acute treatment with CGP-40116 diminished its induction while the chronic low-dose treatment enhanced a brain tolerance, possibly through the mechanism of chemical preconditioning.

Synthesis of some N-substituted 3,4-pyrroledicarboximides as potential CNS depressive agents.

As a continuation of our work on N-[4-aryl(heteroaryl)piperazin-1-ylalkyl]-3,4-pyrro ledicarboximides, which were characterized by strong analgesic activity and CNS depressive action, several novel N-substituted 3,4-pyrroledicarboximides were prepared and eleven representatives were examined in a series of in vivo CNS tests. A few of these compounds displayed a similar profile of biological selectivity to that of 3,4-pyrroledicarboximides described previously; their structure-activity relationships are discussed.

[The mechanisms of neuronal death and advances in the neural protection in epilepsy]. / Mechanizmy smierci neuronów i postepy neuroprotekcji w padaczce.

Epilepsias are chronic central nervous system diseases which manifest by recurrent seizures. They may be classified into channelopathies resulting from mutations of ionic channels or receptors for neurotransmitters, and epilepsias which are secondary to cortical damage and result from the reconstruction of cortical neural networks. Chronic or generalized seizures initiate processes called the "excititoxic cascade" the effector side of which, quite similar to that of the "ischemic cascade", may lead to neuronal death through either apoptosis or necrosis. Therefore, complementing pharmacological treatment of epilepsia with neuroprotective substances such as free radical scavenger or CDP-choline which blocks the activation of phospholipase A2 may be indicated.

A consensus protocol for the standardization of cerebrospinal fluid collection and biobanking.

There is a long history of research into body fluid biomarkers in neurodegenerative and neuroinflammatory diseases. However, only a few biomarkers in CSF are being used in clinical practice. One of the most critical factors in CSF biomarker research is the inadequate powering of studies because of the lack of sufficient samples that can be obtained in single-center studies. Therefore, collaboration between investigators is needed to establish large biobanks of well-defined samples. Standardized protocols for biobanking are a prerequisite to ensure that the statistical power gained by increasing the numbers of CSF samples is not compromised by preanalytical factors. Here, a consensus report on recommendations for CSF collection and biobanking is presented, formed by the BioMS-eu network for CSF biomarker research in multiple sclerosis. We focus on CSF collection procedures, preanalytical factors, and high-quality clinical and paraclinical information. The biobanking protocols are applicable for CSF biobanks for research targeting any neurologic disease.

Cerebrospinal fluid brain specific proteins in relation to nitric oxide metabolites during relapse of multiple sclerosis.

This study investigated the cerebrospinal fluid (CSF) levels of ferritin, S100B as biomarkers for glial activation and NfH(SM135)--a biomarker of axonal damage--in relation to nitric oxide (NO) metabolites: nitrate and nitrite (NOx) during acute multiple sclerosis (MS) relapse. Thirty-four relapsing-remitting MS (RR-MS) patients during acute relapse and 12 controls were enrolled. Patients were assessed on Expanded Disability Status Scale (EDSS) and underwent lumbar puncture within two weeks following relapse. Twenty patients were available for further follow-up and were assessed on EDSS 6-8 weeks since the relapse onset. The CSF NOx (P<0.0001), NfH(SM135) (P=0.01) and S100B (P=0.009) but not ferritin (P>0.05) were significantly raised in MS group. There was a significant correlation between CSF ferritin and S100B in RR-MS group (P=0.004). CSF NOx did not correlate with S100B and ferritin in study groups. RR-MS patients with detectable NfH(SM135) levels had higher NOx compared with subjects having undetectable NfH(SM135) (P=0.03). In the follow-up study, raised baseline levels of NOx (P=0.016) or NfH(SM135) (P=0.04) inversely correlated with the clinical recovery grade expressed as relative EDSS change between baseline and follow-up. In conclusion, NO metabolites were increased and because of their correlation with a biomarker of axonal degeneration (neurofilaments) and a measure for clinical disability (EDSS), relapse-related nitrosative stress is likely to be relevant to the development of sustained disability in an individual patient.