The aim of this study was to present a family co-segregating myotonic dystrophy type 1 (DM1) and 2 (DM2), and one member affected with neuromyelitis optica (NMO).
Index case underwent cataract ...surgery at age 39. Although she had no muscle symptoms, genetic testing revealed a DM2 mutation and a DM1 protomutation. The patient noticed difficulties in climbing stairs at age 47. Clinical examination showed mild muscle weakness, calf hypertrophy, mild myotonia and several multisystem signs. Patient's mother had DM1 protomutation and clinically exhibited only cataract. Two proband's sisters, one with DM2 mutation and another with DM2 mutation and DM1 protomutation, had a clinical presentation similar to the index case. In addition, the latter also developed NMO.
Our findings suggest that screening for both DM1 and DM2 should be done and a positive result in either gene should not be an indication to stop screening, but to move to the other gene.
Distributions of the Ki-67, TP53, caspase-3 and AIFM1 markers were histologically investigated in the 5th to 9th week developing gonads of 12 human conceptuses using immunohistochemical and ...immunofluorescence methods. Between the 5th and 8th developmental week, proliferation gradually increased in the surface gonad epithelium (26–52 %) and stroma (19–42 %), but then slightly decreased in the surface epithelium (35 %) during the early foetal period. In medulla, low proliferation activity decreased from 15 to 12 % between the 7th and 9th week. At earliest stages of gonadal development, primordial germ cells (PGC) were only rarely TP53 positive. In the 7th and 8th week, almost all PGC-s displayed TP53 positivity, while their number decreased in early fetal period. During the investigated period, caspase-3 reactivity gradually decreased in surface epithelium, while it increased in PGC and medulla of developing gonad AIFM1-positivity first appeared in surface gonad epithelium and then predominantly in PCG-s while caspase-3 characterized different cell populations within the developing gonad. AIFM1 and caspase-3 co-localized only during the migration of PCG-s. The number and distribution of Ki-67, TP53, caspase-3 and AIFM1 reacting cells changed coincidently with development end regression of the sex cords in indifferent and early fetal gonad. Our results indicate that the number of PGC might be controlled by balance of TP53 and AIFM1, leading to caspase-3 independent cell death. Other cell populations are probably eliminated by caspase-3-dependent cell death. Both pathways of cell death seem to operate during early human gonad development, while their intensity varies depending on the cell type and developmental period analysed.
Objectives – The aim of this investigation was to evaluate factors that might influence the health‐related quality of life (HRQoL) in multiple sclerosis (MS) patients in Serbia.
Materials and ...methods – This cross‐sectional study was performed on a group of 156 patients with MS. HRQoL was assessed by using the SF‐36 questionnaire. Expanded Disability Status Scale (EDSS) and Beck Depression Inventory (BDI) scale were assessed as variables affecting the HRQoL of MS patients.
Results – EDSS score correlated negatively with all SF‐36 health dimensions, and the highest statistically significant coefficients were for physical functioning (r = −0.682), and social and role functioning (r = −0.407 and −0.405 respectively). BDI correlated statistically significantly negatively (P < 0.01) with all SF‐36 health dimensions.
Conclusions – Our findings suggest that both disability and depression significantly influence the HRQoL in Serbian MS patients, with depressive symptoms having the major influence.
The choice of appropriate control group(s) is critical in cerebrospinal fluid (CSF) biomarker research in multiple sclerosis (MS). There is a lack of definitions and nomenclature of different control ...groups and a rationalized application of different control groups. We here propose consensus definitions and nomenclature for the following groups: healthy controls (HCs), spinal anesthesia subjects (SASs), inflammatory neurological disease controls (INDCs), peripheral inflammatory neurological disease controls (PINDCs), non-inflammatory neurological controls (NINDCs), symptomatic controls (SCs). Furthermore, we discuss the application of these control groups in specific study designs, such as for diagnostic biomarker studies, prognostic biomarker studies and therapeutic response studies. Application of these uniform definitions will lead to better comparability of biomarker studies and optimal use of available resources. This will lead to improved quality of CSF biomarker research in MS and related disorders.
Interleukin‐6 (IL‐6) and nitric oxide (NO) are implicated in the pathology of multiple sclerosis (MS). We have investigated the levels of these mediators in the cerebrospinal fluid (CSF) from 50 ...patients with MS and 23 control subjects. Mean CSF IL‐6 level was higher in the total MS group in comparison with controls, but not significantly, whilst the difference between patients with stable MS and controls reached the level of statistical significance. Mean CSF nitrite/nitrate level was significantly higher in the total MS group compared with the control group, as well as in active MS patients versus controls. There was significant difference neither in the mean CSF IL‐6 nor in nitrite/nitrate levels between active and stable MS patients. Interestingly, we observed a significant negative correlation between IL‐6 and nitrite/nitrate levels in the CSF in the total MS group. Such a trend existed in both subgroups with active and stable MS, but without reaching the level of statistical significance. Our data further support the involvement of IL‐6 and NO in ongoing pathological processes in MS, suggesting their potential interplay within the central nervous system in this disease.
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.
Multiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system. MS can cause different patterns of motor disturbances and gait ...difficulties in all its main clinical phenotypes: relapsing–remitting (RRMS), secondary-progressive (SPMS) or primary-progressive MS (PPMS). We mesasured gait pattern and characteristics in 54 MS patients, 40 with RRMS and 14 with PPMS. In those two forms we compared effects of dual task paradigm on gait characteristics (motor or mental task performance during gait) and compared gait pattern parameters (gait cycle time, stride length, single and double limb support time, as well as their coefficients of variation). Gait cycle is generally considered as automatically generated rhythmic pattern. However, tasks performed during gait in MS are affecting gait parameters differently. Cycle time is longer and stride length is shorter in RR compared to PP form, while motor and mental tasks are affecting gait parameters of both MS forms in similar manner, increasing their coefficients of variation. Changes in gait parameters and characteristics in RRMS and PPMS forms might be the consequences of different internal and external interactions. Those differences could help to design and separate treatment strategies for different MS forms.
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