Comparison of multiple sclerosis patients with or without rebound activity after fingolimod cessation: Five-year clinical outcomes.

BACKGROUND: Patients with multiple sclerosis (MS) who discontinue fingolimod might present with rebound activity. The reasons for the development of rebound have been identified, but there are limited data on the long-term clinical outcomes of these patients. This study aimed to compare the long-term outcomes of patients with MS with and without rebound activity after fingolimod discontinuation. METHODS: A total of 31 patients who discontinued fingolimod for various reasons with a minimum follow-up of 5 years were included in the study. Of these, 10 were assigned to the rebound group and 21 to the non-rebound group. Clinical and demographic data and 5-year clinical outcomes of both groups were prospectively examined. RESULTS: At fingolimod initiation, there were no significant differences in age, disease duration, and Expanded Disability Status Scale (EDSS) score. The annualized relapse rate (ARR) was significantly higher in the rebound group than in the non-rebound group before the fingolimod treatment (p = 0.005). In the rebound group, EDSS scores 2 months after rebound treatment and at the 5-year follow-up were not significantly different than before fingolimod initiation (p = 0.14 and p = 0.46, respectively). The last recorded EDSS was significantly higher in the non-rebound group than in the rebound group (3.6 ± 2.3 vs. 2.15 ± 1.4, p = 0.045). At the last follow-up, one patient was diagnosed with secondary progressive multiple sclerosis in the rebound group (10%), and 11 patients were in the non-rebound group (52.4%, p = 0.05). CONCLUSION: When rebound activity is well-monitored and treated after fingolimod discontinuation, no overall EDSS change is expected in the long-term follow-up.

Retrospective analysis of effectiveness of fingolimod in real life setting in Turkey (REFINE).

BACKGROUND: During multiple sclerosis (MS) treatment different modes of action such as lateral (interferon beta to glatiramer acetate or glatiramer acetate to interferon beta) or vertical (interferon beta/glatiramer acetate to fingolimod) drug switch can be performed. This study aims to investigate the clinical effectiveness of switching from the first-line injectable disease modifying treatments (iDMTs) to fingolimod (FNG) compared to switching between first-line iDMTs. METHODS: This is a multicenter, observational and retrospective study of patients with relapsing-remitting MS who had lateral and vertical switch. The observation period included three key assessment time points (before the switch, at switch, and after the switch). Data were collected from the MS patients' database by neurologists between January 2018 and June 2019. The longest follow-up period of the patients was determined as 24 months after the switch. RESULTS: In 462 MS patients that were included in the study, both treatments significantly decreased the number of relapses during the postswitch 12 months versus preswitch one year while patients in the FNG group experienced significantly fewer relapses compared to iDMT cohort in the postswitch 12 months period. FNG cohort experienced fewer relapses than in the iDMT cohort within the postswitch 2 year. The mean time to first relapse after the switch was significantly longer in the FNG group. DISCUSSION: The present study revealed superior effectiveness of vertical switch over lateral switch regarding the improvement in relapse outcomes. Patients in the FNG cohort experienced sustainably fewer relapses during the follow-up period after the switch compared the iDMT cohort. Importantly, switching to FNG was more effective in delaying time to first relapse when compared with iDMTs.

Treatment of multiple sclerosis-related trigeminal neuralgia with onabotulinumtoxinA.

BACKGROUND: The effectiveness of onabotulinumtoxinA (BTX-A) has been established in primary trigeminal neuralgia (TN). However, to the best of our knowledge, the efficacy of BTX-A in secondary TN has not yet been studied. OBJECTIVE: This study aimed to investigate the efficacy of BTX-A treatment in patients with multiple sclerosis-related trigeminal neuralgia (TN-MS) and compare the efficacy of BTX-A treatment between patients with primary trigeminal neuralgia (TN-P) and patients with TN-MS. METHODS: This was a retrospective medical record-review study. Demographic and clinical features and severity and frequency of pain before and 2 weeks after the BTX-A administration were extracted from the patient files. BTX-A was injected into the painful area subcutaneously and/or submucosally. BTX-A injections were performed by the same physician using the same methods. A reduction in severity and/or frequency of pain ≥50% was considered therapeutic efficacy. RESULTS: Fifty-three patients were included in this study. We classified 22 (42%) as TN-P and 31 (58%) as TN-MS. Treatment with BTX-A was effective in 16 of 31 (52%) patients with TN-MS and 10 of 22 (45%) with TN-P. BTX-A treatment was less effective in patients with a history of interventional treatments and more effective in patients with concomitant continuous pain (p = 0.007; odds ratio [OR]: 0.020-0.53 and p = 0.047; OR: 0.046-0.98, respectively). CONCLUSION: The BTX-A treatment was found to be effective in at least half of our cohort with TN-MS. Concomitant continuous pain and history of interventional treatments to the trigeminal nerve or ganglion might be predictive factors for the efficacy of BTX-A treatment.

Safety of SARS-CoV-2 vaccination in patients with Behcet's syndrome and familial Mediterranean fever: a cross-sectional comparative study on the effects of M-RNA based and inactivated vaccine.

Most of the published data relate to classical forms of rheumatic diseases (RD) and information on rare inflammatory disorders such as Behçet's syndrome (BS) and familial Mediterranean fever (FMF) is limited. We studied the frequency of side effects and disease flares after COVID-19 vaccination with either Pfizer/BioNTech or Sinovac/CoronaVac in 256 patients with BS, 247 with FMF, and 601 with RD. Telephone interviews were conducted using a questionnaire survey in a cross-sectional design in patients with BS, FMF, and RD followed by a single university hospital. Study participants were vaccinated either with CoronaVac (BS:109, FMF: 90, and RD: 343,) or BioNTech (BS: 147, FMF: 157 and RD: 258). The majority have received double dose (BS: 94.9%, FMF 92.3% and RD: 86.2%). BioNTech ensured a significantly better efficacy than CoronaVac against COVID-19 in all patient groups (BS: 1.4% vs 10.1%; FMF: 3.2% vs 12.2%, RD:2.7% vs 6.4%). Those with at least one adverse event (AE) were significantly more frequent among those vaccinated with BioNTech than those with CoronaVac (BS: 86.4% vs 45%; FMF: 83.4% vs 53.3%; and RD: 83.3% vs 45.5%). The majority of AEs were mild to moderate and transient and this was true for either vaccine. There were also AEs that required medical attention in all study groups following CoronaVac (BS: 5.5%, FMF: 3.3%, and RD:2.9%) or BioNTech (BS: 5.4%, FMF: 1.9%, and RD: 4.7%). The main causes for medical assistance were disease flare and cardiovascular events. Patients with BS (16.0%) and FMF (17.4%) were found to flare significantly more frequently when compared to those with RD (6.0%) (p < 0.001). This was true for either vaccine. BS patients reported mainly skin-mucosa lesions; there were however, 11 (4.3%) who developed major organ attack such as uveitis, thrombosis or stroke. Flare in FMF patients were associated mainly with acute serositis with or without fever. Arthralgia/arthritis or inflammatory back pain were observed mainly in the RD group. Our study demonstrates that BS and FMF patients vaccinated with either CoronaVac or BioNTech demonstrated similar AE profile and frequency compared to RD patients. AEs that required physician consultation or hospitalization occurred in all study groups after either CoronaVac or BioNTech. Increased frequency of flares in BS and FMF compared to that seen in RD might reflect defects in innate immunity and deserves further investigation. Caution should be required when monitoring these patients after vaccination.

The efficiency of mirror therapy on drop foot in Multiple Sclerosis Patients.

INTRODUCTION: Although the effectiveness of mirror therapy (MT) has been proved in stroke persons, there is no scientific evidence about the results in people with multiple sclerosis. The aim was to investigate whether adding MT to exercise training and neuromuscular electrical stimulation (NMES) has any effect on clinical measurements, mobility, and functionality in people with multiple sclerosis (MS). METHODS: Ambulatory people with MS, with unilateral drop foot, were included. MT group (n = 13) applied bilateral ankle exercise program with mirror following NMES for 3 days a week at hospital and exercise program for 2 days a week at home. Control group (n = 13) performed same treatment without mirror box (6 weeks). The later 6 weeks both groups performed only exercise program. Clinical measurements included proprioception, muscle tone of plantar flexor muscles (MAS), muscle strength of dorsiflexor, ankle angular velocity, and range of motion (ROM) of ankle. Functionality (Functional Independence Measurement-FIM), mobility (Rivermead Mobility Index-RMI), ambulation (Functional Ambulation Scale-FAS), duration of stair climb test, and 25-foot walking velocity were assessed at the beginning, in 6th and 12th weeks. RESULTS: More positive improvements were obtained in MT group than control group in terms of range of motion (0.012), muscle strength (0.008), proprioception (0.001), 25 feet walking duration (0.015), step test duration (0.001), FAS (0.005), RMI (0.001), and FIM (0.001) after 6 weeks treatment. It was seen that this improvement maintained to 12th week on all clinical and functional measurements (p < .05). CONCLUSION: The trial revealed that adding MT to exercise training and NMES has more beneficial effects on clinical measurements, mobility, and functionality in people with multiple sclerosis with unilateral drop foot.

Parry-Romberg syndrome: is it a "relapsing-remitting" disease?

Parry-Romberg syndrome, also known as progressive hemifacial atrophy, is a rare, slowly progressive disorder characterized by unilateral, painless atrophy of the skin and subcutaneous tissue of the face. Neurological manifestations such as epilepsy, migraine and trigeminal neuralgia are relatively common and accompany in 15-20% of cases. Various etiologies such as infection, trauma, embryonic developmental dysfunction, sympathetic dysfunction and autoimmune disorders have been suggested as possible causes. Here we describe a 37-year-old woman whose disease manifested with dynamic contrast enhanced white matter changes over a period of two years, suggesting a "relapsing-remitting" course. Besides the inflammatory activity, positive serum-autoantibodies, inflammatory findings in cerebrospinal fluid, and an overlapping systemic autoimmune disorder may further support the hypothesis of autoimmune-inflammatory mediated pathogenesis.

The persistence versus interchangeability of migraine and tension-type headaches in a 5-year population-based validated survey.

OBJECTIVE: The aim of this population-based validated study was to determine the course of tension-type headache and migraine and to evaluate the predictors of persistence. METHODS: We evaluated the course of headache in a large population from the first assessment in 2008 through a second assessment in 2013. Then we examined the factors associated with persistent migraine and persistent tension-type headache. RESULTS: Our study in 2013 revealed that only 42.9% of definite migraineurs in 2008 received the same diagnosis again, and of the remaining migraineurs 23.3% were newly diagnosed as definite tension-type headache; 11.6% evolved into probable tension-type headache, 6.4% changed to probable migraine, and 15.8% were headache free. The 17.7% of patients with definite tension-type headache in 2008 were newly diagnosed as having probable tension-type headache, 14.7% as having definite migraine, 6.4% as having probable migraine, and 28.9% as headache free in 2013, and only 32.3% received the definite tension-type headache diagnosis again. Binary logistic regression analysis showed nausea, throbbing and severe headache were the significant parameters for persistent migraine. A multiple regression analysis model with stepwise variable selection revealed that nausea, throbbing and severe headache and osmophobia remained in the final model as predictors of migraine persistence. We found no predictive factor for persistent tension-type headache. CONCLUSION: Migraine and tension-type headache did not seem to show a simple bidirectional linear worsening from headache-free state to definite migraine or vice versa, hence the transitions between them are more chaotic, reflecting that there are still unknown modifiers and modulators. Certain headache characteristics of migraine might predict persistent migraine.

Myelopathy in Behçet's disease: The Bagel Sign.

OBJECTIVE: To describe the clinical and distinctive imaging features of myelopathy associated with Behçet's disease (BD). METHODS: We evaluated the records of patients meeting the following criteria: (1) fulfillment of the International Study Group criteria for BD; (2) clinically suggestive of myelopathy; (3) simultaneous spinal cord and brain magnetic resonance images (MRIs) within 1 month of acute worsening of myelopathy; and (4) follow-up duration ≥ 1 year after initial MRI evaluation. Patients not fulfilling all inclusion criteria and having MRIs with poor quality or missing sequences were excluded. RESULTS: In 11 patients (9 men, 2 women), we studied 14 MRIs during distinct myelopathy episodes and nine follow-up MRIs. Two distinct MRI patterns of spinal cord involvement were described according to T2-weighted (T2W) axial images: (1) "Bagel Sign" pattern: a central lesion with hypointense core and hyperintense rim with or without contrast enhancement; and (2) "Motor Neuron" pattern: a symmetric involvement of the anterior horn cells. Bagel Sign was present in 13 of 14 myelopathy episodes whereas Motor Neuron pattern was observed in 1 of 14 MRIs. Of the 13 MRIs with Bagel Sign long myelopathy (n = 9), both long and short myelopathy (n = 2) and short myelopathy (n = 2) was observed. All patterns cleared with some residual lesions after steroid use and immunomodulation with associated clinical recovery in patients. INTERPRETATION: The signal characteristics of the Bagel Sign potentially represent venous engorgement and/or acute blood products within the spinal cord. To our knowledge, Bagel Sign has not been observed in other forms of longitudinal myelopathy outside of BD, including neuromyelitis optica. Ann Neurol 2017;82:288-298.

Determinants of glucose metabolism and the role of NPY in the progression of insulin resistance in chronic migraine.

Background Chronic migraine has a well-documented association with increased insulin resistance and metabolic syndrome. The hypothalamus may play a role in the progression of insulin resistance in chronic migraine through the regulation of orexigenic peptides such as neuropeptide Y. Insulin resistance may lead to increased risk of future type 2 diabetes mellitus in patients with chronic migraine, which is more likely to occur if other pathogenetic defects of type 2 diabetes mellitus, such as impaired pancreatic ß-cell functions and defects in intestinal glucagon-like peptide-1 secretion after meals. We studied the relationship of fasting neuropeptide Y with insulin resistance, ß-cell function, and glucagon-like peptide-1 secretion in non-obese female chronic migraine patients. We also aimed to investigate glucose-stimulated insulin and glucagon-like peptide-1 secretions as early pathogenetic mechanisms responsible for the development of carbohydrate intolerance. Methods In this cross-sectional controlled study, 83 non-obese female migraine patients of reproductive age categorized as having episodic migraine or chronic migraine were included. The control group consisted of 36 healthy females. We studied glucose-stimulated insulin and glucagon-like peptide-1 secretion during a 75 g oral glucose tolerance test. We investigated the relationship of neuropeptide Y levels with insulin resistance and ß-cell insulin secretion functions. Results Fasting glucose levels were significantly higher in migraine patients. Plasma glucose and insulin levels during the oral glucose tolerance test were otherwise similar in chronic migraine, episodic migraine and controls. Patients with chronic migraine were more insulin resistant than episodic migraine or controls ( p = 0.048). Glucagon-like peptide-1 levels both at fasting and two hours after glucose intake were similar in chronic migraine, episodic migraine, and controls. Neuropeptide Y levels were higher in migraineurs. In chronic migraine, neuropeptide Y was positively correlated with fasting glucagon-like peptide-1 levels (r = 0.57, p = 0.04), but there was no correlation with insulin resistance (r = 0.49, p = 0.09) or ß-cell function (r = 0.50, p = 0.07). Discussion Non-obese premenopausal female patients with chronic migraine have higher insulin resistance, but normal ß-cell function is to compensate for the increased insulin demand during fasting and after glucose intake. Increased fasting neuropeptide Y levels in migraine may be a factor leading to increased insulin resistance by specific alterations in energy intake and activation of the sympathoadrenal system.

Retinal nerve fiber layer structure abnormalities in patients with Neuro-Behcet's disease.

PURPOSE: Our aim was the evaluation of retinal nerve fiber layer (RNFL) and central macular thickness (CMT) in patients with Neuro-Behcet's disease (NBD) and to compare the results with healthy control subjects. METHODS: We recruited 50 eyes of 25 patients with NBD and 42 eyes of 21 age-matched healthy control subjects. Patients and control subjects underwent a thorough ophthalmic examination, including retinal nerve fiber layer and macular thickness measurements by optical coherence tomography. RESULTS: No significant difference was found between groups for age, sex, intra-ocular pressure and central corneal thickness measurements. The average RNFL in patients with NBD was significantly lower than that of healthy controls (86.92 ± 18.36 µm vs. 99.74 ± 8.73 µm; p = 0.00). There was significant thinning of the RNFL in three of four quadrants of the peripapillary area, superior (107.22 ± 30.91 µm vs. 125.57 ± 20.97 µm; p = 0.00), inferior (110.36 ± 25.57 µm vs. 132.19 ± 12.71 µm; p = 0.00) and nasal (68.84 ± 18.47 µm vs. 74.98 ± 11.42 µm; p = 0.05), in patients with NBD. Average CMT was significantly lower in NBD patients than in control subjects (244.06 ± 26.25 µm vs. 261.69 ± 25.71 µm; p = 0.00). CONCLUSIONS: There are significant differences in average RNFL and CMT between the two groups. RNFL and CMT thicknesses are reduced in patients with NBD compared with the healthy controls.

Migraine incidence in 5 years: a population-based prospective longitudinal study in Turkey.

BACKGROUND: The incidence of migraine has been investigated only in a few studies worldwide and it is not known in our country. We, therefore, aimed to estimate the migraine incidence in a previously accomplished population-based prevalence study sample of 5323 individuals in the year 2008. METHODS: The former Turkish headache prevalence study has been completed as a nationwide, randomized, home-based study of face-to-face examination by physicians trained for headache diagnosis by using ICHD criteria. Five years after this study an optimized survey including 50 questions was performed to estimate the migraine incidence in migraine-free individuals in the previous study, with a 56.4 % responder rate. Two validation studies for this survey were performed prior and after the study each in 100 subjects by comparing the gold standard of expert diagnosis of headache, showing high rate of reliability (Crohnbach alpha: 0.911 and 0.706, respectively). RESULTS: Migraine incidence was estimated as 2.38 % (2.98 % in women and 1.93 % in men) per year in 2563 migraine-free individuals; if the population at risk is defined as the group without any headaches, the migraine incidence decreased to 1.99 %. The chronic migraine (CM) incidence [without medication overuse (MOH)] was 0.066 % and that of MOH was 0.259 %. We found a significant burden of the disease on the occupational functionality as well as on social and family life, even in the early years of the migraine. The family history of headaches especially in the fathers could be useful to predict new cases of migraine, besides the well-known risk factor, diagnosis of depression, whereas income and education did not seem to relate to migraine onset. CONCLUSIONS: Our study with a large population-based nation-wide sample, using ICHD-II criteria, with structured headache interviews as well as blinded re-validation of the questionnaire diagnoses showed a 2.38 % incidence rate of migraine in Turkey, higher than most of the other previous reports; a finding which could be related to genetic factors and also to the methodological differences in the study designs. Moreover the incidence of CM was found to be 0.066 %.

A polysomnographic and clinical study of sleep disorders in patients with Behçet and neuro-Behçet syndrome.

Brainstem is the most common site of involvement in neuro-Behçet syndrome (NBS). On the other hand, the critical importance of this anatomical region in the regulation of sleep has been disregarded in the literature. We aimed to investigate the microstructure of sleep in patients with Behçet syndrome (BS) and NBS. Patients were allocated to 2 groups: (1) BS without any neurological involvement and (2) NBS with brainstem lesions only. A control group was also enrolled in this study. The comparison of polysomnographic parameters between all patients (BS and NBS) with the control group showed that sleep onset was longer (p = 0.006), the duration of superficial NREM sleep stage (N2) was significantly longer (p = 0.018), and the respiratory disturbance index was significantly higher (p = 0.034) in patients. Sleep apnea and restless legs syndrome are more commonly observed in BS and NBS. Our findings emphasize the importance of questioning the quality of sleep and its disorders in patients with BS in order to better handle the common somatic complaints in these patients, such as fatigue or daytime sleepiness

Clinical and radiological features in CADASIL and NOTCH3-negative patients: a multicenter study from Turkey.

BACKGROUND: The diversity of clinical presentation and neuroimaging findings of CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) from different regions of the world has not yet been studied in depth. Here we investigated the variability of clinical, radiological and genetic data of 48 patients analyzed for NOTCH3 mutation in Turkey. METHODS: Clinical evaluation was made according to a preformed questionnaire. Cranial neuroimaging findings were determined on the basis of T1, T2, FLAIR and proton-density magnetic resonance scans. For genetic analysis, polymerase chain reaction was performed with primers flanking exons 2-6 and 11 of NOTCH3 gene. RESULTS: Twenty-five patients (52.1%) were diagnosed as CADASIL with NOTCH3 mutation, while 23 patients (47.9%) had no mutation (NOTCH3-negative patients). The mean age and age at stroke onset were lower in male CADASIL patients (p < 0.03). A family history of migraine (p = 0.012), stroke (p < 0.001), recurrent strokes (p = 0.020) and dementia (p = 0.012) was more common in CADASIL patients. Temporal pole involvement was more common in CADASIL patients (p = 0.004). CONCLUSION: It is of clinical importance to identify the heterogeneity of CADASIL from different countries due to a low correlation of clinical and radiological data with respect to NOTCH3 mutation.

Multiple sclerosis during adalimumab treatment in a case with ankylosing spondylitis.

Ankylosing spondylitis is a chronic and progressive inflammatory disease involving the sacroiliac joints with HLA-B27 positivity in 85% of the patients and radiologically evidence of sacroiliitis. It is associated with several extraarticular manifestations, but neurological complications are rare. Occurrence of multiple sclerosis in patients with ankylosing spondylitis has been reported in limited cases. Adalimumab, a TNF-α antagonist, offers a significant improvement in ankylosing spondylitis and is considered to be less immunogenic and more tolerable than other TNF-α blockers. A case of multiple sclerosis coexisted with HLA-B27 positive ankylosing spondylitis after treated with adalimumab was reported.

BAb and MxA as functional biomarkers in routine clinical laboratories for the determination of anti-IFN-beta antibodies and their bioactivity levels in multiple sclerosis patients.

In MS patients under IFNß treatment to seek alternative treatments timely is important that anti-IFNß antibodies and/or in vivo biologic activity loss detection in these. The most common diagnostic markers used for this purpose are BAb, Nab, and MxA. In this article, we aimed to establish the availability and feasibility of the correlation between BAb and MxA gene expression (mRNA) levels using evaluation of responses to IFNß treatment for MS patients with a routine laboratory follow-up strategy in a major Turkish MS center. Bab seropositivity was determined in blood samples of 218 MS patients treated with different IFNß preparations and MxA mRNA levels were measured in 128 patients among the total population. BAb seropositivity ratios to im INF-ß 1a, scINF-ß 1a, and sc INF-ß 1b were 21.4%, 28.6%, and 70.4%, respectively (total 40%), and total loss of bioactivity (MxA mRNA) were 9.3%, 9.5%, and 11.6%, respectively (total 10.2%). The correlation between high BAb titers and low MxA mRNA levels was highly significant (P = 0.00003). Our data indicate that there is a good correlation between especially high BAbs levels and diminished MxA mRNA levels.

The impact of depression and ghrelin on body weight in migraineurs.

BACKGROUND: Comorbidity of migraine with anxiety and depression may play a role in the link between migraine and obesity. We examined the moderating and mediating roles of ghrelin in the relationship between depression (and anxiety) and body weight in newly diagnosed migraineurs. METHODS: Participants were 63 newly diagnosed migraine patients (using the ICHD-II criteria) and 42 healthy volunteers. Body mass index (BMI) was calculated by measuring height and weight. Ghrelin was assessed at fasting. Depression was assessed with the Hamilton Depression scale, and anxiety with the Hamilton Anxiety scale. RESULTS: The data did not support the mediating role of ghrelin in the relationship between depression (or anxiety) and BMI for either the migraine or the control group. The interaction between ghrelin and depression as well as anxiety was significant for the migraine group, but not for the control group. Depressed (or anxious) migraineurs had a positive association between ghrelin and BMI, whereas for the non-depressed (or non-anxious) migraineurs this association was negative. CONCLUSIONS: Depression and anxiety moderated the effect of ghrelin on BMI for migraineurs. Management of anxiety and depression might be regarded as part of migraine treatment.

Ocrelizumab in pediatric multiple sclerosis.

BACKGROUND: Ocrelizumab is a recombinant humanized anti-CD20 monoclonal IgG1, approved by FDA and EMA for adult patients with multiple sclerosis (MS). The data on the efficacy and safety of Ocrelizumab for pediatric MS cases are limited. OBJECTIVE: Here, we describe pediatric relapsing-remitting MS (P-RRMS) cases who were treated with Ocrelizumab as a disease-modifying drug. METHOD: P-RRMS cases who were started Ocrelizumab below 18 years-of-age and followed-up >12 months with Ocrelizumab treatment were included. The primary end-points were annualized relapse rate (ARR) and magnetic resonance imaging (MRI) activity (new/enlarging T2 lesions and new gadolinium (Gd) enhancing lesions). The secondary end-points were the percentage of patients who remain relapse-free and/or free from Gd enhancing lesions, Expanded Disability Status Scale (EDSS) score, and the safety profile of Ocrelizumab. RESULTS: Of 18 P-RRMS cases receiving Ocrelizumab, 10 patients fulfilled the inclusion criteria for our study. The median duration of follow-up under Ocrelizumab was 28,3 months (min: 15 months, max: 46 months). Mean ARR decreased from 2.01 (±0.71) to 0 during the follow-up of Ocrelizumab treatment (P < 0.0001). None of the patients had MRI activity during the treatment. Mean EDSS decreased from 1.75 (±1.09) to 1.20 (±0.63) from the initiation of Ocrelizumab to the last follow-up of the patients (P = 0.024). None of the patients had serious side effects, except one patient who experienced anaphylaxis. CONCLUSION: Ocrelizumab can be considered a safe and effective treatment option in highly active P-RRMS.

Analysis of determinants of treatment change in adult paediatric-onset MS patients.

BACKGROUND: Paediatric-onset multiple sclerosis (POMS) is increasing worldwide and represents approximately 5% of all MS cases. Although this patient group has similar characteristics to the adult group, it is important for this patient group to receive effective treatment due to the early onset of cognitive involvement, higher lesion burden, and secondary progression at an earlier age than adults. In this study, we aimed to evaluate the factors that cause treatment change in POMS patients. MATERIAL AND METHOD: Adult patients with a first MS attack at age 18 years or younger who were followed up with the diagnosis of MS at the Clinical Neuroimmunology and Demyelinating Diseases outpatient clinic of Cerrahpasa Medical School between 1987 and 2020 were included in our study. Patient files were reviewed retrospectively, and demographic and clinical characteristics, imaging, first attack characteristics, and treatment change were noted. We included 269 patients with a definite diagnosis of MS in the study, and these patients were evaluated in two groups: negative for treatment change and positive for treatment change. RESULTS: Multifocal involvement was detected more frequently in the group with treatment change (p = 0,049). Cerebellar involvement as a first attack symptom was more common in male patients (p = 0,023) The age at first MS attack was found to be younger (p = 0,006), and the disease duration was longer in the positive for treatment change group (p = 0,003). Spinal cord involvement was more common in the positive for treatment change group (p = 0,016). Abnormal VEP findings were observed more frequently in the group without treatment change (p = 0.018). In multivariant analysis, spinal cord involvement, younger age at first attack, and abnormal VEP findings in the group without treatment change were found to be significant. Among the reasons for treatment change, the most common reason was radiological and clinical progression. CONCLUSION: The higher inflammatory load in POMS patients compared with adults necessitates early initiation of treatment in this group and timely treatment change to prevent disability. Furthermore, this patient group should be followed closely and receive effective treatment.

Prospective outcome analysis of multiple sclerosis cases reveals candidate prognostic cerebrospinal fluid markers.

BACKGROUND: Predicting the long-term disability outcomes of multiple sclerosis (MS) cases is challenging. OBJECTIVE: We prospectively analysed our previous MS cohort with initial cerebrospinal fluid (CSF) proteomics data to reveal disability markers after 8.2±2.2 years of follow-up. METHODS: Patients with regular follow-up visits were assigned into two groups: those with an age-related MS severity (ARMSS) score ≥5 (unfavourable course group, N = 27) and ARMSS score <5 (favourable course group, N = 67). A machine learning-based algorithm was applied to reveal candidate poor prognosis-associated initial CSF proteins, which were measured in an independent MS cohort (verification group, N = 40) by ELISA. Additionally, the correlation of initial clinical and radiological parameters with long-term disability was analysed. RESULTS: CSF alpha-2-macroglobulin (P = 0.0015), apo-A1 (P = 0.0016), and haptoglobin (P = 0.0003) protein levels, as well as cerebral lesion load (>9 lesions) on magnetic resonance imaging, gait disturbance (P = 0.04), and bladder/bowel symptoms (P = 0.01) were significantly higher in the unfavourable course group than in the favourable course group. Optic nerve involvement evident on initial magnetic resonance imaging (P = 0.002) and optic neuritis (P = 0.01) were more frequent in the favourable course group. CONCLUSION: The herein identified initial CSF protein levels, in addition to the clinical and radiological parameters at disease onset, have predictive value for long-term disability in MS cases.