Severe lymphopenia after subcutaneous cladribine in a patient with multiple sclerosis: To vaccinate or not?

Objective: To describe a fatal case of influenza A pneumonia in a patient with severe lymphopenia after receiving subcutaneous cladribine to treat her multiple sclerosis (MS). Methods: Case report. Results: A 53-year-old woman developed fatal influenza pneumonia associated with grade 4 lymphopenia two months after receiving a total dose of 60mg subcutaneous cladribine. Despite treatment with oseltamivir, her condition deteriorated and the patient passed away after developing respiratory failure. Conclusion: Cladribine-related lymphopenia is usually mild to moderate, however severe lymphopenia may occur. People with MS, especially those who are immunosuppressed, should be offered the inactivated influenza vaccine annually

Subcutaneous cladribine to treat multiple sclerosis : experience in 208 patients

Objective: To report on safety and effectiveness of subcutaneous cladribine (Litak®) in multiple sclerosis (MS) patients. Methods: Litak® was offered to MS-patients irrespective of disease course. Litak® 10 mg was administered for 3–4 days during week 1. Based on lymphocyte count at week 4, patients received another 0–3 doses at week 5. A second course was administered 11 months later. Follow-up included adverse events, relapses, expanded disability status scale (EDSS), 9-hole-peg and Timed-25-foot-walking tests, no-evidence-of-disease-activity (NEDA), no-evidence-of-progression-or-active-disease (NEPAD), MRI, cerebrospinal fluid (CSF) neurofilament light chain (NfL), and lymphocyte counts. Results: In all, 208 patients received at least one course of treatment. Age at baseline was 44 (17–72) years and EDSS 0–8.5. Cladribine was generally well tolerated. One myocardial infarction, one breast cancer, and three severe skin reactions occurred without long-term sequelae. Two patients died (one pneumonia, one encephalitis). Lymphopenia grade 3 occurred in 5% and grade 4 in 0.5%. In 94 out of 116 pwMS with baseline and follow-up (BaFU) data after two treatment courses, EDSS remained stable or improved. At 18 months, 64% of patients with relapsing MS and BaFU data (n = 39) had NEDA. At 19 months, 62% of patients with progressive MS and BaFU data (n = 13) had NEPAD. Of n = 13 patients whose CSF-NfL at baseline was elevated, 77% were normalised within 12 months. Conclusions: Litak® was well tolerated. Effectiveness in relapsing MS appeared similar to cladribine tablets and was encouraging in progressive MS. Our data suggest cladribine may be safe and effective in MS-patients irrespective of their disease stage

Evidence for a window of enhanced plasticity in the human motor cortex following ischemic stroke

Background In preclinical models, behavioral training early after stroke produces larger gains compared with delayed training. The effects are thought to be mediated by increased and widespread reorganization of synaptic connections in the brain. It is viewed as a period of spontaneous biological recovery during which synaptic plasticity is increased. Objective To look for evidence of a similar change in synaptic plasticity in the human brain in the weeks and months after ischemic stroke. Methods We used continuous theta burst stimulation (cTBS) to activate synapses repeatedly in the motor cortex. This initiates early stages of synaptic plasticity that temporarily reduces cortical excitability and motor-evoked potential amplitude. Thus, the greater the effect of cTBS on the motor-evoked potential, the greater the inferred level of synaptic plasticity. Data were collected from separate cohorts (Australia and UK). In each cohort, serial measurements were made in the weeks to months following stroke. Data were obtained for the ipsilesional motor cortex in 31 stroke survivors (Australia, 66.6 ± 17.8 years) over 12 months and the contralesional motor cortex in 29 stroke survivors (UK, 68.2 ± 9.8 years) over 6 months. Results Depression of cortical excitability by cTBS was most prominent shortly after stroke in the contralesional hemisphere and diminished over subsequent sessions (P = .030). cTBS response did not differ across the 12-month follow-up period in the ipsilesional hemisphere (P = .903). Conclusions Our results provide the first neurophysiological evidence consistent with a period of enhanced synaptic plasticity in the human brain after stroke. Behavioral training given during this period may be especially effective in supporting poststroke recovery

Cervical Spine Manipulations: Role of Diagnostic Procedures, Effectiveness, and Safety from a Rehabilitation and Forensic Medicine Perspective: A Systematic Review

Background: Cervical spine manipulations (CSM) have been performed for centuries and are a widely practiced intervention to manage cervical spine musculoskeletal disorders. We aimed to perform an overview of the literature concerning the effects and the adverse events of CSM in the Physical and Rehabilitation Medicine (PRM) field with a forensic medicine perspective. Methods: A search in the scientific literature (PubMed, Google Scholar, PEDro and Cochrane) was carried out from inception until October 2020. Results: Fourteen articles were included in this narrative summary. The possible development of side effects requires a careful mandatory balance of benefits and risks even when there is an indication for this approach. Moreover, a qualified professional is essential to perform CSM–a non-invasive therapeutic procedure that can be potentially harmful. Conclusions: In conclusion, it is essential to perform the diagnosis, to treat, and to manage complications within the PRM field, both for the reduction of malpractice claims and, most importantly, for the safety of the patient

Cladribine Personalised Dosing to Treat Active Multiple Sclerosis - Follow-up in 250 patients

This is the accepted manuscript of an article published online: 1. ACTRIMS Forum 2021 – Poster Presentations. Multiple Sclerosis Journal. 2021;27(1_suppl):15-122. doi:10.1177/1352458521101590

Evidence for a window of enhanced plasticity in the human motor cortex following ischemic stroke

Background In preclinical models, behavioral training early after stroke produces larger gains compared with delayed training. The effects are thought to be mediated by increased and widespread reorganization of synaptic connections in the brain. It is viewed as a period of spontaneous biological recovery during which synaptic plasticity is increased. Objective To look for evidence of a similar change in synaptic plasticity in the human brain in the weeks and months after ischemic stroke. Methods We used continuous theta burst stimulation (cTBS) to activate synapses repeatedly in the motor cortex. This initiates early stages of synaptic plasticity that temporarily reduces cortical excitability and motor-evoked potential amplitude. Thus, the greater the effect of cTBS on the motor-evoked potential, the greater the inferred level of synaptic plasticity. Data were collected from separate cohorts (Australia and UK). In each cohort, serial measurements were made in the weeks to months following stroke. Data were obtained for the ipsilesional motor cortex in 31 stroke survivors (Australia, 66.6 ± 17.8 years) over 12 months and the contralesional motor cortex in 29 stroke survivors (UK, 68.2 ± 9.8 years) over 6 months. Results Depression of cortical excitability by cTBS was most prominent shortly after stroke in the contralesional hemisphere and diminished over subsequent sessions (P = .030). cTBS response did not differ across the 12-month follow-up period in the ipsilesional hemisphere (P = .903). Conclusions Our results provide the first neurophysiological evidence consistent with a period of enhanced synaptic plasticity in the human brain after stroke. Behavioral training given during this period may be especially effective in supporting poststroke recovery