Paroxysmal extreme pain disorder in family with c.3892G > T (p.Val1298Phe) in the SCN9A gene mutation - case report.

BACKGROUND: To describe the clinical phenotype of paroxysmal extreme pain disorder, an autosomal dominant condition in four members in one family with the mutation NM_002977.3:c.3892G > T (p.Val1298Phe) in the SCN9A gene. Clinical examinations and details from members of one Polish family were collected, including age at onset, features of attacks, problems between attacks, investigational results, treatments tried, and evolution over time. CASE PRESENTATION: Twenty two individuals from this family with paroxysmal extreme pain disorder were identified. Seven of them presented clinical manifestation of paroxysmal extreme pain disorder, of which and in four were identified missens mutations in the SCN9A gene (NM_002977.3:c.3892G > T). The onset of the disorder took place in the neonatal period or infancy and persists throughout life. Autonomic manifestations predominate with extreme pain, skin flushing and harlequin colour change were observed in all. Attacks of excruciating deep burning pain often appear in the rectal, or jaw areas, but also diffuse in the body. Attacks are triggered by factors such as: defecation, eating, pressure and emotion. Carbamazepine and other antiepileptic drugs were only partly effective in almost all, but the response was incomplete. CONCLUSIONS: Paroxysmal extreme pain disorder is a hereditary sodium channelopathy with pain and an autonomic nervous system dysfunction. Paroxysmal extreme pain disorder is rare, so far only 500 cases of both women and men have been described in world literature.

Effectiveness of dimethyl fumarate as first line therapy in MS patients - one center real life observation study.

Interferon ß, glatiramer acetate and dimethyl fumarate are first line of disease-modifying therapies for patients who have got relapsingremitting multiple sclerosis (RRMS). Currently, there are no precise guidelines for modifying treatment. This is the individual decision of the attending physician, which should take into account both the clinical course of the disease and the patient's preferences. Therefore, possible findings of this study may potentially improve treatment strategy and could be helpful for the clinicians to select the most appropriate therapy. AIM: The aim of this study was to evaluate and compare activity of multiple sclerosis one year before and one year after switching treatment from interferon ß or glatiramer acetate to dimethyl fumarate. The reasons for treatment modification and impact of these reasons on therapy effectiveness were studied as a secondary outcome. MATERIALS AND METHODS: This observational and retrospective study among patients with RRMS lasted for 2 years and was conducted at one medical center. Participants of the study were aged 19-61 years. All of them had been initially treated with disease-modifying drugs (DMDs) by injection: interferon or glatiramer acetate. After one-year observation patients switched therapy to dimethyl fumarate (DMF) for various reasons. RESULTS: 62 adult patients received interferon beta or glatiramer acetate in the first year. After a year all of them switched from that therapy to dimethyl fumarate. Patients in all treatment groups had similar demographic and clinical characteristics at baseline. The most common reason for change in interferon ß group were adverse effects or clinical ineffectiveness. Patients from glatiramer acetate group most often changed their therapy due to new lesions on MRI scans. Presented study shows a statistically significant decrease in radiological relapse when changing treatment from glatiramer acetate to dimethyl fumarate. At the same time, switching from interferon to dimethyl fumarate reduced the number of clinical relapses. There was no statistically significant difference in EDSS scores before and after treatment change in interferons' ß and glatiramer acetate's groups. CONCLUSIONS: The results of our study show that patients with progression of the disease should be treated with another medication. Further research is necessary to develop therapeutic position that supports therapeutic decision in an early period of MS. The observation of the presented group of patients will be continued.