Highly Active Multiple Sclerosis

A 16-year-old girl was evaluated for symptoms of thoracic myelitis with sensory loss below T12, gait difficulty, constipation, and incomplete bladder emptying. On evaluation, she had a flat affect, normal cranial nerve function, and normal motor examination findings. Deep tendon reflexes were symmetric, and plantar responses were flexor. She had a sensory level at T12 with diminished vibratory sense distal to the knees and normal coordination and gait. Magnetic resonance imaging of the brain, cervical spine, and thoracic spine showed a high burden of disease, with multiple enhancing lesions indicative of highly active disease. Spinal fluid analysis showed 16 white blood cells/µL with 95% lymphocytes; protein, 70 mg/dL; 7 unique oligoclonal bands; and immunoglobulin G index, 0.87. Neurocognitive testing showed normal scores overall, and psychiatric evaluation indicated major depressive disorder. She was given a diagnosis of relapsing-remitting multiple sclerosis, highly active. On initial evaluation for thoracic myelitis, intravenous methylprednisolone was given, with resolution of bladder and bowel symptoms and 75% recovery of sensory loss. High-dose interferon beta-1a was then initiated. At age 28 years, she had worsening left hemiparesis of 1 month’s duration. Neurologic examination showed word-finding difficulty, gaze-evoked horizontal nystagmus, moderate left-sided spastic hemiparesis in a pyramidal distribution, brisk reflexes with an extensor plantar response on the left, sensory ataxia in the left leg, and a hemiparetic gait. Intravenous methylprednisolone was given, with minimal improvement. She then received plasmapheresis with about 50% recovery of power. The patient was seropositive for antibodies to JC polyoma virus. Despite the increased risk of progressive multifocal leukoencephalopathy, natalizumab was reinitiated considering the even higher risk of long-term disability due to continued active disease (highly active multiple sclerosis). Her therapy was transitioned to teriflunomide. Six months later she returned with new right leg weakness and received high-dose intravenous corticosteroids for 5 days, followed by rituximab infusion. On follow-up neuroimaging, breakthrough disease activity was noted, and her therapy was switched to alemtuzumab. Highly active multiple sclerosis is characterized by frequent clinical episodes, with or without high disease activity on neuroimaging as evidenced by multiple enhancing lesions or interval new lesion formation, and disability accrual. It includes a spectrum of patients with clinical and radiologic evidence of ongoing disease activity who have no response to adequate treatment with multiple sclerosis disease-modifying therapy.

Selective cognitive dysfunction and physical disability improvement after autologous hematopoietic stem cell transplantation in highly active multiple sclerosis

The aim was to assess the cognitive dysfunction and physical disability after autologous hematopoietic stem cell transplantation (AHSCT), to explore the potential factors influencing disability regression after AHSCT and to estimate the safety of low-dose immunosuppressive therapy in highly active Multiple Sclerosis (MS) patients. In single-center prospective study patients who failed to conventional therapies for highly active relapsing MS underwent the AHSCT. The disability was followed up with Expanded Disability Status Scale and cognition with Brief International Cognitive Assessment for Multiple Sclerosis. Twenty four patients [18 (72.0%) female] underwent AHSCT. Two patients of 13 had one relapse during the first year and three patients—during the second year after AHSCT. Disability regression was found in 84.6% of patients. The scores of information processing speed and verbal learning were significantly higher at month 12 after AHSCT. The clinical variable that explained the disability regression at months 6 and 12 after AHSCT was the disability progression over 6 months before AHSCT. No transplant related-deaths were observed. Selective cognitive improvement was found after AHSCT in MS patients. The disability may be temporarily reversible after AHSCT in a significant proportion of highly active RMS patients if AHSCT is well-timed performed.

Recommendations for switching patients with highly active multiple sclerosis from other disease modifying drugs for multiple sclerosis to cladribine tablets

The need for optimal treatment of the active forms of multiple sclerosis (MS), especially highly active MS (HAMS), poses a number of difficult problems for specialists, including not only the choice of a highly effective disease-modifying drug for MS (DMDMS), but also conditions for the timely and safe switching from other DMDMS. A group of expert neurologists from various clinics in Russia presents a consensus on the practical aspects of switching patients with HAMS from other DMDMS to cladribine tablets, which has been registered in Russia in March 2020. The paper discusses indications for changing therapy and gives indications, contraindications, and conditions for initiating cladribine therapy. It details the procedure and results of the expert consensus, on the basis of which the recommendations have been developed to switch to cladribine tablets from each of the DMDMS registered in Russia for the treatment of MS.

Experience with cladribine tablets for highly active multiple sclerosis in everyday clinical practice

Cladribine tablets are a new drug for the immune reconstitution therapy of highly active multiple sclerosis (HAMS). After discussing the characteristics of action of the drug in clinical trials, the authors give their own experience of its use in the Moscow Multiple Sclerosis Center.Objective: to assess their own experience with cladribine tablets in the treatment of HAMS patients in everyday clinical practice.Patients and methods: In 2018–2020, a total of 14 patients with HAMS and an average exacerbation frequency of 2.42 per year (34 exacerbations) received a full cycle of cladribine therapy. The patients independently purchased the drug for individual indications. Prior to starting therapy and every subsequent 6 months, all the patients underwent contrast-enhanced magnetic resonance imaging (MRI) of the brain, cervical and thoracic spine, and chest X-ray, Expanded Disability Status Scale (EDSS) scoring, clinical blood analysis, lymphocyte subpopulation estimation, biochemical blood analysis. The levels of leukocytes, lymphocytes, and lymphocyte subpopulations were estimated after one- and two-year cladribine tablet therapy cycles.Results and discussion. During a two-year cladribine tablet therapy cycle, there were only 2 exacerbations (0.1 per year); the EDSS values stabilized, while they slightly decreased; according to MRI, the number of foci declined substantially from 78 (an average of 3.12 per image) before treatment to 6 (an average of 0.2 per image) after 2 years of treatment. No serious adverse events were recorded in patients taking cladribine tablets. By the end of the first year of treatment, the level of lymphocytes returned to normal in all the patients. The similar picture was noted after the second cycle of therapy. More than two-thirds of patients showed a decline in CD19+ B lymphocytes. An anti-B-cell effect was recorded even in patients who had normal absolute lymphocyte counts, as shown by clinical blood analysis. The findings demonstrated the efficacy and safety of cladribine tablets in patients with HAMS.Conclusion. Cladribine tablets are a highly effective treatment for HAMS.

Elevated D-dimer as an immediate response to alemtuzumab treatment

Alemtuzumab as a treatment of highly active multiple sclerosis causes a rapid decrease in inflammatory activity due the lysis of immune cells. Subsequent cytokine release determines the infusion-associated reaction that is a frequent adverse event of alemtuzumab treatment. Recently, serious cardiovascular and thrombotic adverse reactions following alemtuzumab infusion have been described. In our study, the dynamics of coagulation parameters were analyzed in 13 multiple sclerosis patients treated with alemtuzumab. An immediate, significant increase in the level of D-dimer was observed after the first administration of alemtuzumab. This observation provides evidence of coagulation activation and the potential risk of thrombotic complications with this therapy. Prophylactic low molecular weight heparin pretreatment maybe considered in patients receiving alemtuzumab.