David E. Jones

Overview and safety of fingolimod hydrochloride use in patients with multiple sclerosis

Introduction: Fingolimod (Gilenya®, FTY720) is an oral sphingosine-1-phosphate analogue that was approved by the FDA in 2010 for the treatment of relapsing forms of multiple sclerosis (MS). Fingolimod’s mechanism of action is primarily related to lymphocyte sequestration in primary and secondary lymphoid tissues. Phase III trials demonstrated a reduction in annualized relapse rate and MRI progression in fingolimod-treated subjects compared with both placebo and IFN-β-treated subjects. Frequent adverse effects include fatigue, gastrointestinal disturbance, headache and upper respiratory tract infection. More serious, but rare, adverse events associated with fingolimod include atrioventricular block, symptomatic bradycardia, herpetic viral infections and macular edema. Areas covered: We discuss the mechanism of action, pharmacokinetics, clinical efficacy and safety profile of fingolimod in patients with relapsing MS. Expert opinion: Fingolimod is an effective treatment for relapsing MS and its oral route of administration may be preferred by some. Fingolimod is generally well tolerated but requires diligence in patient selection and monitoring. Additional information is needed regarding risk of infection, malignancy and rebound disease with long-term use of fingolimod.

Cryptococcal meningitis after fingolimod discontinuation in a patient with multiple sclerosis

Fingolimod (Gilenya, Novartis) is an oral sphingosine-1-phosphate analogue used in the treatment of relapsing multiple sclerosis (MS). Fingolimod treatment is associated with relative lymphopenia and was associated with an increased risk of herpes infection in clinical trials. In the post-marketing setting, fingolimod has been associated with several cases of cryptococcal meningitis, recently prompting an update to its prescribing information. To date, all cases have been associated with active treatment with fingolimod. In this report, we describe the first case of cryptococcal meningitis diagnosed after fingolimod discontinuation.

The state of multiple sclerosis: current insight into the patient/health care provider relationship, treatment challenges, and satisfaction

Background Managing multiple sclerosis (MS) treatment presents challenges for both patients and health care professionals. Effective communication between patients with MS and their neurologist is important for improving clinical outcomes and quality of life. Methods A closed-ended online market research survey was used to assess the current state of MS care from the perspective of both patients with MS (≥18 years of age) and neurologists who treat MS from Europe and the US and to gain insight into perceptions of treatment expectations/goals, treatment decisions, treatment challenges, communication, and satisfaction with care, based on current clinical practice. Results A total of 900 neurologists and 982 patients completed the survey, of whom 46% self-identified as having remitting-relapsing MS, 29% secondary progressive MS, and 11% primary progressive MS. Overall, patients felt satisfied with their disease-modifying therapy (DMT); satisfaction related to comfort in speaking with their neurologist and participation in their DMT decision-making process. Patients who self-identified as having relapsing-remitting MS were more likely to be very satisfied with their treatment. Top challenges identified by patients in managing their DMT were cost, side effects/tolerability of treatment, and uncertainty if treatment was working. Half of the patients reported skipping doses, but only 68% told their health care provider that they did so. Conclusion Several important differences in perception were identified between patients and neurologists concerning treatment selection, satisfaction, expectations, goals, and comfort discussing symptoms, as well as treatment challenges and skipped doses. The study results emphasize that patient/neurologist communication and patient input into the treatment decision-making process likely influence patient satisfaction with treatment.

A framework of care in multiple sclerosis, part 2: Symptomatic care and beyond

The Consortium of Multiple Sclerosis Centers (CMSC) convened a Framework Taskforce composed of a multidisciplinary group of clinicians and researchers to examine and evaluate the current models of care in multiple sclerosis (MS). The methodology of this project included analysis of a needs assessment survey and an extensive literature review. The outcome of this work is a two-part continuing education series of articles. Part 1, published previously, covered the updated disease phenotypes of MS along with recommendations for the use of disease-modifying therapies. Part 2, presented herein, reviews the variety of symptoms and potential complications of MS. Mobility impairment, spasticity, pain, fatigue, bladder/bowel/sexual dysfunction, cognitive dysfunction, and neuropsychiatric issues are examined, and both pharmacologic and nonpharmacologic interventions are described. Because bladder and bowel symptoms substantially affect health-related quality of life, detailed information about elimination dysfunction is provided. In addition, a detailed discussion about mental health and cognitive dysfunction in people with MS is presented. Part 2 concludes with a focus on the role of rehabilitation in MS. The goal of this work is to facilitate the highest levels of independence or interdependence, function, and quality of life for people with MS.

Intramedullary spinal cord metastasis from salivary ductal carcinoma of the parotid gland mimicking transverse myelitis in a patient with radiologically isolated syndrome

Intramedullary spinal cord metastases (ISCMs) are rare lesions but their presence should not be underestimated in a cancer patient with rapidly progressive neurological compromise. Due to similar timing of clinical progression and imaging characteristics, these lesions may be misdiagnosed as transverse myelitis, an inflammatory disorder of the spinal cord that may be idiopathic or secondary to other diseases including infections, connective tissue disorders, nutritional deficiencies, and demyelinating disorders. We present a case of a 44 year-old male with a history of parotid gland metastatic salivary ductal carcinoma (SDC) and incidental demyelinating white matter lesions on brain magnetic resonance imaging (MRI) diagnosed as radiologically isolated syndrome with a CSF that was positive for oligoclonal bands. The patient initially presented with mid-thoracic dermatomal numbness, bilateral lower extremity weakness, and neurogenic bladder. MRI spine demonstrated an enhancing T5-7 intramedullary lesion initially diagnosed as transverse myelitis. After progressing to complete motor and sensory loss below T6 despite high-dose intravenous steroids and plasmapheresis, surgical biopsy was undertaken. Intraoperative findings revealed an intramedullary tumor for which a subtotal resection was performed. Pathology was consistent with a metastatic deposit from the patients primary parotid SDC. The patient underwent postoperative chemotherapy but expired due to systemic disease progression seven months following surgery without neurological improvement. This is the first reported case of ISCM from a primary SDC. The median survival is 6 months for patients with ISCMs treated surgically. The goals of surgery are spinal cord decompression, functional preservation, and tissue diagnosis.

Identification and validation of clinically meaningful benchmarks in the 12-item Multiple Sclerosis Walking Scale.

Background: The 12-item Multiple Sclerosis Walking Scale (12-MSWS) is a validated questionnaire which assessed walking function; it has been widely adopted in multiple sclerosis (MS) clinical research. Objective: Identify and validate clinically meaningful 12-MSWS benchmarks in MS. Methods: Cross-sectional study of 159 MS patients permitted identification of clinically meaningful 12-MSWS benchmarks based on their relationship to real-life anchors. Identified 12-MSWS benchmarks were then validated in a second population of 96 subjects using measures of ambulation, cognition, and patient-reported outcomes. Results: 12-MSWS score of 0–24.99 was associated with working outside the home and assistance-free mobility; 25–49.99 was associated with gait disability and difficulty doing housework; 50–74.99 was associated with unemployment, government healthcare, cane use, and difficulty performing instrumental activities of daily living (IADLs); and 75–100 was associated with change in occupation due to walking, mobility impairment requiring bilateral assistance, and inability to perform IADLs. During the validation step, strong linear associations were identified between 12-MSWS benchmarks and other MS-related disability outcome measures, including ambulatory and non-ambulatory measures. Conclusion: We have identified clinically meaningful 12-MSWS benchmarks which define four groups differentiated by increasing levels of mobility impairment and associated loss of functional independence. These data provide insight into how 12-MSWS translate to meaningful functional limitations in MS.

Splenic marginal zone lymphoma: An indolent malignancy leading to the development of neurolymphomatosis

Acute neuropathic pain and weakness with a sensory level in a patient with a history of lymphoma has a broad differential diagnosis. Evaluation of such a presentation often includes MRI, neurophysiologic studies, and cerebrospinal fluid evaluation. We report a patient with splenic marginal zone lymphoma who developed acute weakness, sensory loss, and neuropathic pain due to neurolymphomatosis.

Rehabilitation in multiple sclerosis: Commentary on the recent AAN systematic review

Multiple sclerosis (MS) is one of the most common causes of nontraumatic neurologic disability in young adults in the United States. Historically, MS care focused on rehabilitation and symptomatic management; however, this focus broadened with the development of disease-modifying therapies (DMTs), resulting in pharmacologic treatments that effectively reduce relapses and potentially slow the progression of disability. Consequently, DMTs often dominate many discussions regarding MS care, regardless of the fact that they do not reverse disability or restore function, arguably the primary goal of those with MS. Comprehensive, multidisciplinary care goes beyond the management of DMTs in MS treatment plans and strives to improve patient outcomes, functionality, and quality of life, goals that will likely prove to hold considerable importance as health care reimbursement transitions from a fee-for-service to a value-based paradigm. It is therefore likely that achieving improvement in some of the outcomes delineated in the American Academy of Neurologys (AAN) quality measures for MS will necessitate involvement of rehabilitation specialists.1