Pattern electroretinogram (PERG) and pattern visual evoked potential (PVEP) in the early stages of Alzheimer’s disease

Alzheimer’s disease (AD) is one of the most common causes of dementia in the world. Patients with AD frequently complain of vision disturbances that do not manifest as changes in routine ophthalmological examination findings. The main causes of these disturbances are neuropathological changes in the visual cortex, although abnormalities in the retina and optic nerve cannot be excluded. Pattern electroretinogram (PERG) and pattern visual evoked potential (PVEP) tests are commonly used in ophthalmology to estimate bioelectrical function of the retina and optic nerve. The aim of this study was to determine whether retinal and optic nerve function, measured by PERG and PVEP tests, is changed in individuals in the early stages of AD with normal routine ophthalmological examination results. Standard PERG and PVEP tests were performed in 30 eyes of 30 patients with the early stages of AD. The results were compared to 30 eyes of 30 normal healthy controls. PERG and PVEP tests were recorded in accordance with the International Society for Clinical Electrophysiology of Vision (ISCEV) standards. Additionally, neural conduction was measured using retinocortical time (RCT)—the difference between P100-wave latency in PVEP and P50-wave implicit time in PERG. In PERG test, PVEP test, and RCT, statistically significant changes were detected. In PERG examination, increased implicit time of P50-wave (P < 0.03) and amplitudes reductions in P50- and N95-waves (P < 0.0001) were observed. In PVEP examination, increased latency of P100-wave (P < 0.0001) was found. A significant increase in RCT (P < 0.0001) was observed. The most prevalent features were amplitude reduction in N95-wave and increased latency of P100-wave which were seen in 56.7% (17/30) of the AD eyes. In patients with the early stages of AD and normal routine ophthalmological examination results, dysfunction of the retinal ganglion cells as well as of the optic nerve is present, as detected by PERG and PVEP tests. These dysfunctions, at least partially, explain the cause of visual disturbances observed in patients with the early stages of AD

Self-reported quality of life in multiple sclerosis patients: preliminary results based on the Polish MS Registry

Waldemar Brola,1 Piotr Sobolewski,2 Małgorzata Fudala,1 Stanisław Flaga,3 Konrad Jantarski,4 Danuta Ryglewicz,5 Andrzej Potemkowski6 1Department of Neurology, Specialist Hospital, Końskie, 2Department of Neurology, Holy Spirit Specialist Hospital, Sandomierz, 3AGH University of Science and Technology, Krakow, 4Swietokrzyski Regional Branch of the Polish National Health Fund (NFZ), Kielce, 5First Department of Neurology, Institute of Psychiatry and Neurology, Warsaw, 6Department of Psychology, University of Szczecin, Szczecin, Poland Background: The aim of the study was to analyze selected clinical and sociodemographic factors and their effects on the quality of life (QoL) of multiple sclerosis (MS) patients registered in the Polish MS Registry.Methods: This was a cross-sectional observational study performed in Poland. Data on personal and disease-specific factors were collected between January 1, 2011, and December 31, 2015, via the web portal of the Polish MS Registry. All patients were assessed by a physician and asked to complete the Polish language versions of the following self-evaluation questionnaires: EuroQol 5-Dimensions, EuroQoL Visual Analog Scale, and Multiple Sclerosis Impact Scale. Univariate analysis and logistic regression were performed to determine the factors associated with QoL.Results: The study included 2,385 patients (female/male ratio 2.3:1) with clinically confirmed MS (mean age 37.8&plusmn;9.2 years). Average EuroQol 5-Dimensions index was 0.72&plusmn;0.24, and the mean EuroQoL Visual Analog Scale score was 64.2&plusmn;22.8. The average Multiple Sclerosis Impact Scale score was 84.6&plusmn;11.2 (62.2&plusmn;18.4 for physical condition and 23.8&plusmn;7.2 for mental condition). Lower QoL scores were significantly associated with higher level of disability (odds ratio [OR], 0.932; 95% confidence interval [CI], 0.876&ndash;0.984; P=0.001), age &gt;40 years (OR, 1.042; 95% CI, 0.924&ndash;1.158; P=0.012), longer disease duration (OR, 0.482; 95% CI, 0.224&ndash;0.998; P=0.042), and lack of disease modifying therapies (OR, 0.024; 95% CI, 0.160&ndash;0.835; P=0.024). No significant associations were found between QoL, sex, type of MS course, patient&rsquo;s education, and marital status.Conclusion: The Polish MS Registry is the first national registry for long-term observation that allows for self-evaluation of the QoL. QoL of Polish patients with MS is significantly lower compared with the rest of the population. The parameter is mainly affected by the level of disability, duration of the disease, and limited access to immunomodulatory therapy. Keywords: multiple sclerosis, patient-reported outcomes, quality of life, Polan

The most important psychological and psychosocial needs of Polish multiple sclerosis patients and their significant others

Andrzej Potemkowski,1 Waldemar Brola,2,3 Anna Ratajczak,4 Marcin Ratajczak,5 Mariusz Kowalewski,6 Małgorzata Lewita,6 Katarzyna Kapica-Topczewska,7 Joanna Tarasiuk,7 Adam Stępień,8 Katarzyna Gocyła-Dudar,8 Jacek Zaborski,9 Halina Bartosik-Psujek10 1Department of Clinical Psychology and Psychoprophylaxis, University of Szczecin, 2Department of Neurology, Specialist Hospital, Końskie, 3The Faculty of Medicine and Health Science, Institute of Physiotherapy, Jan Kochanowski University, Kielce, 4Pomeranian Medical University, Szczecin, 5Clinical Trial Center for MS-Patients, Szczecin, 6John Paul II Multiple Sclerosis Rehabilitation Center, Borne Sulinowo, 7Department of Neurology, Medical University of Białystok, Białystok, 8Department of Neurology, Military Institute of Medicine,&nbsp;Warsaw, 9Department of Neurology, Specialist Hospital in Międzylesie, Warsaw, 10Medical Faculty, University of Rzesz&oacute;w, Rzesz&oacute;w,&nbsp;Poland Background: People with multiple sclerosis (MS) and their relatives often have multiple, complex needs which require support from a wide range of services. The aim of the study, the first of its kind in Poland, was to identify the most important needs of patients with MS and their significant others (SO). Methods: A questionnaire developed from focus groups consisting of 20 needs-related statements was administered in seven MS centers to 573 MS patients and 220 SO. The mean age of the patients was 42.61 years old; the mean MS duration was 9.43 years. The respondents were asked to rate the needs statements according to their importance on an 11-point scale. The questionnaire was similar for the MS patients and their SO. Results: The most important needs in the patient group were: to feel needed and efficient in life; to have easy access to professional rehabilitation; and to be sure that doctors are interested in my condition. The three most important needs in the SO group were: to know that relatives/friends feel needed and efficient in life; to have good living conditions; and to be sure that doctors are interested in my relative&rsquo;s/friend&rsquo;s condition. Correlation analysis revealed that in the patients group, there was a positive correlation between patient&rsquo;s age and the importance of factors such as the need for support and interest in their disease from the family doctor (P&lt;0.004), receiving educational materials from an MS clinic (P&lt;0.011), interest from the clinic in life issues of the patient (P&lt;0.001), and the need for access to self-rehabilitation (P&lt;0.003); while the need to continue working part-time was inversely correlated with age (P&lt;0.009). Conclusion: The needs of the MS patients and SO were similar. The data validate the importance of interdisciplinary care for the MS population. Keywords: multiple sclerosis, unmet needs, needs assessment, Polan

Safety and efficacy of opicinumab in patients with relapsing multiple sclerosis (SYNERGY): a randomised, placebo-controlled, phase 2 trial

Background Opicinumab is a human monoclonal antibody against LINGO-1, an inhibitor of oligodendrocyte differentiation and axonal regeneration. Previous findings suggested that opicinumab treatment might enhance remyelination in patients with CNS demyelinating diseases. We aimed to assess the safety and efficacy of opicinumab in patients with relapsing multiple sclerosis.Methods We did a randomised, double-blind, placebo-controlled, dose-ranging, phase 2 study (SYNERGY) at 72 sites in 12 countries. Participants (aged 1858 years) with relapsing multiple sclerosis (relapsing-remitting multiple sclerosis and secondary progressive multiple sclerosis with relapses) were randomised in a 1:2:2:2:2 ratio by an interactive voice and web response system to opicinumab 3 mg/kg, 10 mg/kg, 30 mg/kg, or 100 mg/kg, or placebo. An identical volume of study drug was administered intravenously once every 4 weeks. All participants self-administered intramuscular interferon beta-1a as background anti-inflammatory treatment once a week. The primary endpoint was the percentage of participants achieving confirmed disability improvement over 72 weeks, which was a multicomponent endpoint measured by the Expanded Disability Status Scale, the Timed 25-Foot Walk, the Nine-Hole Peg Test, and the 3 s Paced Auditory Serial Addition Test. The primary endpoint was analysed under intention-to-treat principles. This study is registered at ClinicalTrials.gov, number NCT01864148.Findings Between Aug 13, 2013, and July 31, 2014, 419 patients were enrolled and randomly assigned either placebo (n=93) or opicinumab 3 mg/kg (n=45), 10 mg/kg (n=95), 30 mg/kg (n=94; one patient did not receive the assigned treatment), or 100 mg/kg (n=92). The last patient visit was on March 29, 2016. Confirmed disability improvement over 72 weeks was seen in 45 (49%) of 91 patients assigned to placebo, 21 (47%) of 45 assigned to opicinumab 3 mg/kg, 59 (63%) of 94 assigned to opicinumab 10 mg/kg, 59 (65%) of 91 assigned to opicinumab 30 mg/kg, and 36 (40%) of 91 assigned to opicinumab 100 mg/kg. A linear dose-response in the probability of confirmed disability improvement was not seen (linear trend test p=0.89). Adverse events occurred in 79 (85%) patients assigned placebo and in 275 (85%) assigned any dose of opicinumab. The most common adverse events of any grade in patients assigned any dose of opicinumab included influenza-like illness (140 [43%] with any dose of opicinumab vs 37 [40%] with placebo), multiple sclerosis relapses (117 [36%] vs 30 [32%]), and headache (51 [16%] vs 23 [25%]). Serious adverse events reported as related to treatment were urinary tract infection in one (1%) participant in the the placebo group, suicidal ideation and intentional overdose in one (1%) participant in the 30 mg/kg opicinumab group, bipolar disorder in one (1%) participant in the 100 mg/kg opicinumab group, and hypersensitivity in four (4%) participants in the 100 mg/kg opicinumab group. One patient in the opicinumab 30 mg/kg group died during the study due to a traffic accident, which was not considered related to study treatment.Interpretation Our findings did not show a significant dose-linear improvement in disability compared with placebo in patients with relapsing multiple sclerosis. Further studies are needed to investigate whether some subpopulations identified in the study might benefit from opicinumab treatment at an optimum dose