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.
Multiple sclerosis (MS) is the commonest disabling neurological condition to afflict young adults and therefore has a high social burden. Over several decades, there has been a considerable progress ...in the understanding of the disease pathogenesis as well as in the clinical management of MS patients. The emphasis in managing MS patients has shifted to multidisciplinary teams working in specialist groups. A review of the literature was conducted using MedLine to identify recent advances in MS. The current consensus is that MS is an autoimmune disease triggered by environmental agents acting in genetically susceptible people. Based on that concept, new methods of immune intervention procedures have been introduced into clinical practice. Licensed first-line disease-modifying therapies reduce the MS attack or relapse rate by a third and delaying short-term disease progression. More effective therapies have emerged; however, these are associated with increased risks. New clinical and pathological insights are making us question the aetiology and pathogenesis of MS. The recognition of pathological heterogeneity has raised the question of whether MS is a single disease entity or a syndrome. Recent evidence suggests that the pathological subtype may predict therapeutic response to specific therapies. A new novel auto-antibody has defined a subset of neuromyelitis optica or Devic's disease as being distinct from MS. This is an attractive concept that is not widely accepted. The observation that MS progresses despite immunosuppressive therapy suggests that MS may be a neurodegenerative disease with overlapping immune activation possibly in response to the release of central nervous system auto-antigens. The development of neuroprotective therapies for MS is required to prevent the devastating effects of long-term disability as a result of progressive disease.
This study investigated the cerebrospinal fluid (CSF) levels of ferritin, S100B as biomarkers for glial activation and NfHSM135 — 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), NfHSM135 ( 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 NfHSM135 levels had higher NOx compared with subjects having undetectable NfHSM135 (P = 0.03). In the follow-up study, raised baseline levels of NOx (P = 0.016) or NfHSM135 (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. Multiple Sclerosis 2008; 14: 59—66. http://msj.sagepub.com
Background and purpose
The main objectives of this study were to investigate if epileptic seizures have effects on brain metabolism of β‐amyloid (Aβ), as reflected by cerebrospinal fluid (CSF) levels ...of different isoforms of Aβ 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 Aβx‐38, Aβx‐40, Aβx‐42, Aβ1‐42, soluble APP fragments (sAPP‐α/β), 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 Aβ or sAPP peptides between seizure patients and controls. In patients with rPS, the levels of Aβx‐38 and Aβx‐40 were elevated compared with nSE (P < 0.01), sPS (P < 0.05) and controls (P < 0.05), and Aβx‐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 Aβ or sAPP peptides, our findings suggest that different types of seizures may have different effects on APP metabolism.
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.
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