The use of cladribine in the treatment of multiple sclerosis

Multiple sclerosis (MS) is a chronic inflammatory disease that affects the central nervous system. The cause of MS is still unknown, but it is considered to be multifactorial. A combination of clinical examination, radiological, and laboratory methods according to the McDonald diagnostic criteria confirms the diagnosis with high probability. Management of MS includes disease-modifying drugs that show different levels of efficacy. Cladribine is an antimetabolite drug indicated for the treatment of highly active relapsing-remitting MS based on clinical or imaging features

Differentiation between multiple sclerosis and neuromyelitis optica spectrum disorder

Multiple sclerosis (MS) can sometimes be misdiagnosed with neuromyelitis optica spectrum disorder (NMOSD). NMOSD is a chronic disorder of the brain and spinal cord dominated by inflammation of the optic nerve (optic neuritis) and inflammation of the spinal cord (myelitis)

Do we need broad immunological work-up in all patients with CIS?

BACKGROUND: The aim of this study was to determine the prevalence of altered immunological tests and their clinical significance in patients with clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS). ----- PATIENTS AND METHODS: The information was gathered from medical records of patients hospitalized in the Referral Center for Demyelinating Diseases in the 2008-2010 period. All patients had ANA, ENA profile, ANCA, aCl IgG and IgM, C3, C4, CH50, anti-TPO, AST and RF antibodies tested. ----- RESULTS: From 726 patients with CIS that were reviewed, the complete battery of immunological tests was performed in 418 of them (57.6%), representing our cohort. Altered tests were found in 235 patients (56.2%); 73 (17.4%) had positive antinuclear antibodies, 14 (3.3%) had positive ENA, 47 (11.2%) had positive aCl IgG, 83 (19.8%) had positive aCl IgM, and 13 (3.1%) had anti TPO antibodies. We found no correlation between ANA, aCl IgG or IgM positivity (ANA vs aCL IgG p=0.554; ANA vs aCL IgM p=0.19; aCL IgG vs aCL IgM, p=0.155). None of the patients had any clinical manifestations other than MS symptoms. ----- CONCLUSION: These results indicate that significant number of patients with CIS have altered immunological tests but nevertheless none of them had clinical expression of any other autoimmune disease making them clinically insignificant. In conclusion there is no need to perform extensive immunological work-up in all patients with CIS. Contrary, our results argue for more focused testing rather than a battery of screening tests

Auditory evoked potentials and vestibular evoked myogenic potentials in evaluation of brainstem lesions in multiple sclerosis

OBJECTIVE: The aim of this study was to determine the roles of magnetic resonance imaging (MRI), auditory evoked potentials (AEP) and vestibular evoked myogenic potentials (VEMP) in the evaluation of brainstem involvement in multiple sclerosis (MS). ----- PATIENTS AND METHODS: Altogether 32 patients with the diagnosis of MS participated in the study. The following data was collected from all patients: age, gender, Expanded Disability Status Scale (EDSS) score, brainstem functional system score (BSFS) (part of the EDSS evaluating brainstem symptomatology), and involvement of the brainstem on the brain MRI. AEP and ocular VEMP (oVEMP) and cervical VEMP (cVEMP) were studied in all patients. ----- RESULTS: BSFS, MRI, AEP, oVEMP and cVEMP involvement of the brainstem was evident in 9 (28.1%), 14 (43.8%), 7 (21.9%), 12 (37.5%) and 10 (31.0%) patients, respectively. None of the tests used showed statistically significant advantage in the detection of brainstem lesions. When combining oVEMP and cVEMP 18 (56.3%) patients showed brainstem involvement. This combination showed brainstem involvement in greater percentage than BSFS or AEP, with statistical significance (p=0.035 and p=0.007, respectively). ----- CONCLUSION: VEMP is a reliable method in detection of brainstem involvement in MS. It is comparable with MRI, but superior to clinical examination or AEP

Procjena oštećenja moždanoga debla vestibularnim evociranim miogenim potencijalima (VEMP) u relapsno-remitirajućoj multiploj sklerozi

Background: The aim of this study was by using VEMP method to determine the proportion of patients with RRMS who have subclinical damage of the brainstem and to determine differences in oVEMP and cVEMP between the different clinical presentation of the disease, as well as to determine the role of latencies, corrected amplitudes and new VEMP variables in the evaluation of brainstem involvement in patients with MS. Patients and methods : The study included 100 patients with RRMS who were divided into two groups - patients with and without clinically detectable lesions of the brainstem. The control group consisted of 50 healthy volunteers. For patients with MS EDSS and BSFS were calculated and data related to the disease course, as well as data related to the neuroanatomical localization of lesions on MRI in the brainstem were taken. All study subjects underwent VEMP and the analysis of variables were done. Results: All patients with MS regardless of the clinical presence of lesions of the brainstem showed statistically significant differences in oVEMP latencies variables compared to healthy controls. Significant difference was obtained between patients with MS and healthy controls regarding analysis of conduction blocks, whereas statistically significant difference was reached for all explored blocks in MS patients with clinical brainstem lesion compared to patients with MS without clinical lesions of the brainstem. In patients with MS without clinical lesions of the brainstem pathological VEMP response was detected in 94%, while in patients with MS and present clinical signs of brainstem lesion pathological VEMP response was detected in 90% of patients. VEMP score analysis showed a statistically significant difference for the variables VEMP SCM and VEMP total scores in the group of patients with clinical signs of brainstem lesions in comparison with patients with MS without clinical lesions of the brainstem. In both groups of patients with MS, the variable OM and VEMP total revealed more pathological findings than MRI and demonstrated abnormal VEMP findings in patients with normal MRI of the brainstem which could imply the existence of brainstem lesion. Conclusion : VEMP enhanced by using new VEMP variables is sensitive method in the verification of existing and identification of asymptomatic lesions of the brainstem

Correlation of the VEMP score, ambulation and upper extremity function in clinically isolated syndrome

OBJECTIVE: To investigate the correlation of the vestibular evoked myogenic potential (VEMP) score with Timed 25-Foot Walk (T25FW), 9-Hole Peg Test (9HPT), Paced Auditory Serial Addition Test (PASAT) and EDSS in patients with multiple sclerosis (MS). ----- METHODS: This prospective, cross sectional study included 52 patients with clinically isolated syndrome (CIS). Cervical VEMP (cVEMP) and ocular VEMP (oVEMP), analyzed in the form of the cVEMP, oVEMP and VEMP scores, T25FW, 9HPT, PASAT and Expanded Disability Status Scale (EDSS) were performed. ----- RESULTS: The only predictor of walking impairment in this study was general disability as measured by the EDSS, after controlling for age, gender, PASAT and EDSS the effect of VEMP score was non-significant (p=0.419). 9HPT of the dominant hand did not correlate with the oVEMP score (rs=0.258, p=0.065), however after controlling for age, gender, PASAT and EDSS, the effect of the oVEMP score on 9HPT of the dominant hand was statistically significant (p=0.017). After controlling for age, gender and oVEMP score, the effect of the PASAT on 9HPT variable for the non-dominant hand was statistically significant (p=0.001). ----- CONCLUSION: We found possible effects of brainstem dysfunction on walking impairment, however they were not seen after correction for EDSS and cognitive dysfunction. On the other hand, dominant hand function seems to be influenced by upper brainstem dysfunction measured with oVEMP, while cognitive dysfunction is related to non-dominant hand function

Stromalna reakcija u sinkronom in situ i invazivnom urotelnom karcinomu mokraćnog mjehura

The aim was to investigate stromal reaction, including inflammation and stromal desmoplasia in in situ and invasive urothelial carcinoma of urinary bladder and to determine the possible value of reactive stromal changes in the diagnosis of lamina propria invasion. We analyzed specimens from 24 consecutive patients with synchronous in situ and invasive urothelial carcinoma in the same biopsy. Specimens were obtained by transurethral resection, fixed and routinely stained with H&E and Mallory method. Immunohistochemistry was performed by monoclonal antibodies to vimentin, smooth muscle actin and desmin. The intensity of immunostaining was graded semiquantitatively on a scale of 0-3, and expressed as 0 = 0%; 1 = up to 33%; 2 = more than 33% to 66%; and 3 = more than 66% of positive stromal cells. The intensity of inflammation was labeled as 0 = no inflammation, 1 = weak, 2 = moderate, and 3 = dense inflammatory reaction. Mallory trichrome method showed predominantly no staining or weak green staining in 14/24 invasive and 20/24 in situ urothelial carcinomas (p>0.05). There was statistically significantly increased vimentin and smooth muscle actin immunostaining in the stroma of invasive carcinoma as compared with in situ carcinoma (p0,05). Utvrđena je statistički značajno jača reakcija na vimentin i glatkomišićni aktin u stromi invazivnih karcinoma u odnosu na karcinom in situ (p<0,05). Upalna reakcija je bila statistički značajno jača u invazivnim karcinomima (p<0,05). Imunohistokemijska izraženost miofibroblastičnih biljega bila je statistički značajno jača u invazivnim urotelnim karcinomima. Ovakvi rezultati mogu pomoći u dijagnozi invazije lamine proprije u invazivnom karcinomu mokraćnog mjehura