BMC Neurology

In the US, the approved multiple sclerosis (MS) oral disease-modifying therapies (ODMTs) are fingolimod (FTY), teriflunomide (TFN), and dimethyl fumarate (DMF). FTY and TFN are recommended with once-daily doses with no up-titration, whereas DMF treatment is recommended twice-daily (BID) and is initiated with a 7-day starter dose of 120 mg BID before up-titration to the maintenance dose of 240 mg BID. Limited information exists regarding real-world ODMT prescribing patterns to aid physician/patient decision-making. Eligible patients for this retrospective medical record review were ≥18 years, had one visit related to ODMT initiation (index visit), and ≥1 visit within 12 months before and after the index visit. Primary objectives were to assess post-index ODMT persistency (i.e., discontinuation), prescribing patterns (medication switching, dose up-titrations, dose reduction, re-starts, and add-ons) and medical resource utilization (office-visits, MRI procedures, and mobility indicators) at distinct time windows of 3, 6, 9, and 12 months. Chi-square or Wilcoxon Rank Sum tests were used for 3-way ODMT group comparisons. Medical records of 293 MS-diagnosed patients using ODMTs were abstracted from 19 US-based neurology clinics between December 31, 2010 and June 30, 2014 (FTY: 101; DMF: 133; TFN: 59). Persistency rates among ODMT groups were similar. MS-related medication switching, dose reduction, re-starts, and add-ons were infrequently observed and were similar across ODMT groups. Of DMF patients with a confirmed starting dose of 120 mg BID with ≥12 months follow-up (n = 26), the percentage who were prescribed dose up-titrations to the recommended maintenance DMF dose was 23.1 % at 1–3 months, 26.9 % at 4–6 months, 42.3 % at 7–9 months, and 0 % at 10–12 months. There were no significant differences at any time window among the ODMT groups in the number of office visits or percent of patients receiving MRIs. Mobility indicator patterns (proportion of patients with abnormal gait, wheelchair use, etc.) were consistent over time. There was no difference in persistency, prescribing patterns (medication switching, dose reduction, re-starts, and add-ons) or medical resource utilization (office-visits, MRI procedures, and mobility indicators) among the ODMTs. However, in a small sub-group of patients, delays of up to 9 months in DMF dose-up titration to the recommended maintenance dose were observed.

The widespread adoption of electronic health records provides new opportunities to better predict which patients are likely to suffer a stroke. Using electronic health records, we assessed the correlation of different laboratory tests to future occurrences of a stroke. We examined the electronic health records of 2.4 million people over a two year time span. These records contained 26,964 diagnoses of stroke. Using Cox regression analysis, we measured whether any one of 1796 different laboratory tests were effectively correlated with a future diagnosis of stroke. We identified 38 different laboratory tests that had significant short-term (two year) prognostic value for a future diagnosis of stroke. For each of the 38 laboratory tests we also compiled the Kaplan-Meier survival curve, and relative risk ratio that the test confers. Several dozen laboratory tests are effective short-term correlates of stroke.

Immune checkpoint inhibitor (ICI) combined with chemotherapy has exhibited promising results in small sample studies of pancreatic cancer patients. The efficacy of toripalimab, a programmed cell death protein 1 (PD-1) monoclonal antibody has been explored in the previous studies and it was established that immune-related adverse events (irAEs) associated with administration of this drug deserve proper attention and adequate management. A 43-year-old female patient with advanced pancreatic ductal adenocarcinoma (PDAC) was treated with toripalimab in combination with gemcitabine and nab-paclitaxel (T-GA) as the first-line treatment. She developed immune-related encephalopathy with stuttering as the main clinical symptom and Magnetic resonance imaging (MRI) showed multiple cerebral white matter demyelination changes, concomitant with asymptomatic cardiac enzyme elevation and hypothyroidism. The symptoms resolved after the discontinuation of toripalimab and corticosteroid treatment. Stuttering might be an early sign of neurotoxicity which can be easily neglected during the treatment. These findings provide guidance for the identification of these rare and occult neurological irAEs (n-irAEs) in the clinical practice.

Motor neuron disease (MND) is a rapidly progressive, fatal neurodegenerative disease that predominantly affects motor neurons from the motor cortex to the spinal cord and causes progressive wasting and weakening of bulbar, limb, abdominal and thoracic muscles. Prognosis is poor and median survival is 2–3 years following symptom onset. Psychological distress is relatively common in people living with MND. However, formal psychotherapy is not routinely part of standard care within MND Care Centres/clinics in the UK, and clear evidence-based guidance on improving the psychological health of people living with MND is lacking. Previous research suggests that Acceptance and Commitment Therapy (ACT) may be particularly suitable for people living with MND and may help improve their psychological health. To assess the clinical and cost-effectiveness of ACT modified for MND plus usual multidisciplinary care (UC) in comparison to UC alone for improving psychological health in people living with MND. The COMMEND trial is a multi-centre, assessor-blind, parallel, two-arm RCT with a 10-month internal pilot phase. 188 individuals aged ≥ 18 years with a diagnosis of definite, laboratory-supported probable, clinically probable, or possible familial or sporadic amyotrophic lateral sclerosis, and additionally the progressive muscular atrophy and primary lateral sclerosis variants, will be recruited from approximately 14 UK-based MND Care Centres/clinics and via self-referral. Participants will be randomly allocated to receive up to eight 1:1 sessions of ACT plus UC or UC alone by an online randomisation system. Participants will complete outcome measures at baseline and at 6- and 9-months post-randomisation. The primary outcome will be quality of life at six months. Secondary outcomes will include depression, anxiety, psychological flexibility, health-related quality of life, adverse events, ALS functioning, survival at nine months, satisfaction with therapy, resource use and quality-adjusted life years. Primary analyses will be by intention to treat and data will be analysed using multi-level modelling. This trial will provide definitive evidence on the clinical and cost-effectiveness of ACT plus UC in comparison to UC alone for improving psychological health in people living with MND. ISRCTN Registry, ISRCTN12655391. Registered 17 July 2017, https://www.isrctn.com/ISRCTN12655391 . Protocol version: 3.1 (10/06/2020).

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS) with increasing incidence mainly in high-income countries. One explanation of this phenomenon may be a higher prevalence of allergic and autoimmune diseases in industrialized countries as a consequence of otherwise beneficial advances in sanitation (hygiene hypothesis). We investigated environmental factors in early childhood associated with MS. A case-control study was performed of 245 MS patients and 296 population-based controls in Berlin. The study participants completed a standardized questionnaire on environmental factors in childhood and youth, including aspects of personal and community hygiene. Multivariable logistic regression analysis was performed to investigate factors in childhood and youth associated with the occurrence of MS. Mean age was 46 years (range, 20-80) in the MS group and 42 years (range 18-80) in the control group, of which 73.9% in the MS and 61.5% in the control group were female. The multivariable analysis showed that having at least two older siblings (OR 0.54; p = 0.05, for individuals with two older siblings compared to individuals without older siblings), attending a day-care center (OR 0.5; p = 0.004) and growing up in an urban center with more than 100, 000 inhabitants (OR 0.43; p = 0.009) were factors independently associated with a lower chance for MS. The hygiene hypothesis may play a role in the occurrence of MS and could explain disease distribution and increasing incidence.

Cognitive impairment in adult moyamoya disease (MMD) is thought to be the result of ischemic stroke; however, the presence and extent of cognitive decline in asymptomatic patients is unclear. After classification using T2-weighted fluid attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI), a total of 19 MMD patients with a history of cerebral infarction, 21 asymptomatic MMD patients, and 20 healthy controls matched for age, sex, and years of education were prospectively included in this study. A detailed neuropsychological evaluation of two moyamoya subgroups and normal controls was conducted. Asymptomatic patients showed varying degrees of decline in intelligence (Raven’s Standard Progressive Matrices, P = 0.001), spatial imagination (mental rotation, P = 0.014), working memory (verbal working memory-backward digit span, P = 0.011), and computational ability (simple subtraction, P = 0.014; complex subtraction, P < 0.001) compared with normal controls. MMD patients with cerebral infarction had more severe impairment in complex arithmetic (P = 0.027) and word short-term memory (P = 0.01) than those without symptoms. In asymptomatic MMD patients, a variety of cognitive impairment precedes the onset of clinical symptoms such as cerebral infarction, which may be a long-term complication of conservative treatment.

Đau nửa đầu được coi là một căn bệnh có mẫu hình theo ngày và 24 giờ, tuy nhiên sự tồn tại của một nhịp sinh học phổ biến liên quan đến tần suất và mức độ nghiêm trọng của cơn đau nửa đầu vẫn chưa được làm rõ. Nghiên cứu cắt ngang quan sát này nhằm mục đích: 1. Đánh giá nhịp sinh học của thời điểm khởi phát cơn đau nửa đầu trong một quần thể bệnh nhân lớn được chọn tại một trung tâm đau đầu, bao gồm đau nửa đầu cấp tính và mạn tính 2. Phân tích đặc điểm chính của các nhóm thời gian khởi phát khác nhau 3. Xác minh xem các đặc điểm của cơn đau nửa đầu, đặc biệt là những đặc điểm liên quan đến đau nửa đầu mạn tính và gây tàn tật có thể là những yếu tố phân biệt cho nhóm thời gian khởi phát. Chúng tôi đã chọn 786 bệnh nhân đau nửa đầu ngoại trú liên tiếp, những người đã hoàn thành nhật ký đau đầu một cách chính xác trong 3 tháng liên tiếp và đáp ứng chẩn đoán đau nửa đầu không có ánh sáng-MO, đau nửa đầu với ánh sáng điển hình hoặc kết hợp với đau nửa đầu không có ánh sáng - MO/MA và đau nửa đầu mạn tính – CM. Đối với thời gian khởi phát đau đầu, chúng tôi đã xem xét bốn khoảng thời gian, từ 6 đến 12 giờ sáng (sáng), từ 1 đến 6 giờ chiều (chiều), từ 7 đến 11 giờ tối (tối), từ 12 giờ đêm đến 5 giờ sáng (đêm), và một thể loại bổ sung gọi là “bất kỳ lúc nào”. Mỗi khoảng thời gian bao gồm 60 phút trước thời gian tiếp theo (ví dụ: một cơn đau bắt đầu vào 12:30 giờ sáng sẽ được bao gồm trong khoảng thời gian từ 6 đến 12 giờ sáng). Chúng tôi đã đánh giá tất cả bệnh nhân về độ nhạy cảm vùng đầu, các triệu chứng lo âu và trầm cảm, mức độ khuyết tật liên quan đến đau đầu, các đặc điểm giấc ngủ, chất lượng cuộc sống, triệu chứng allodynia và mệt mỏi. Chúng tôi ghi nhận tổng cộng 16,578 cơn đau, phân bổ trong suốt cả ngày. Hầu hết bệnh nhân, bao gồm cả CM, đều đáp ứng tiêu chí cho việc khởi phát “bất kỳ lúc nào”. Khởi phát vào ban đêm có đặc điểm đại diện ít hơn đáng kể trong nhóm MA/MO. Những bệnh nhân có khởi phát vào ban đêm chiếm ưu thế thường lớn tuổi hơn, có thời gian đau nửa đầu dài hơn và thời gian ngủ ngắn hơn. Tuổi và thời gian bị bệnh là những biến số phân biệt các nhóm thời gian khởi phát khác nhau. Hầu hết bệnh nhân đau nửa đầu không báo cáo một hồ sơ sinh học theo nhịp cụ thể về việc xảy ra các cơn đau. Đau nửa đầu thường xuyên, khuyết tật nghiêm trọng, các triệu chứng tâm lý cũng như các dấu hiệu nhạy cảm trung ương không tương ứng với một nhịp sinh học cụ thể về khởi phát cơn đau. Đau nửa đầu khởi phát vào ban đêm dường như là một đặc điểm liên quan đến độ tuổi, xuất hiện trong quá trình bệnh.

Limb-shaking transient ischaemic attacks (TIAs) are an under recognised presentation of severe cerebrovascular disease resulting from cerebral hypoperfusion. Patients present with jerking, transitory limb movements precipitated by change in position or exercise that are often confused with seizure. Cerebral perfusion imaging studies are an important tool available to aid diagnosis. We present the case of a young female who developed limb-shaking TIA in the context of progressive severe intracranial atherosclerotic disease (ICAD). Previous cortical infarction raised suspicion for seizure as a cause of her symptoms. However, single photon emission CT (SPECT) with CT acetazolamide challenge identified severe left hemisphere cerebral hypoperfusion and a diagnosis of limb-shaking TIA was made. Symptoms improved with maximal medical management. This case highlights the importance of cerebral perfusion imaging for diagnostic confirmation as well as therapeutic options available to alleviate symptoms and reduce stroke risk in patients with limb-shaking TIA.

Acute autonomic neuropathy (AAN) is rare disorder with anecdotal report, especially for childhood onset patients. Misdiagnosis or delays in treatment can always be found in clinical practice. We conducted this study to give a description of the manifestations and treatment of AAN in children and therefore help clinicians to make the accurate diagnosis early so that the prognosis of the patients can be improved. A systematic record from 3 clinical centers was used to identify 11 subject, 3 males and 8 females, with clinical diagnosed AAN. The age ranged from 2 years and 4 months to 14 years and 6 months (mean, 9 ± 3.6 years old) and the course from onset to diagnosis ranged from 7 days to 8 months. All children shared prominent initial symptoms, 7 with frequent vomiting and 4 with motor dysfunctions. The condition of 9 patients improved after treatment of IVIg and intravenous glucocorticoid. The clinical manifestations of AAN are diverse, generalized, and non-specific. Gastrointestinal disorders were the most common initial symptoms. Symptoms of gastrointestinal system and abnormal secretion of glands were severe and more common than other symptoms. The mechanism of AAN remains unknown. Although IVIg and intravenous glucocorticoid can be used in clinical practice, there is still no treatment recommendation and further study is needed.