Exploring the High-Grade and Refractory Neurotoxicity of Teclistamab: An Underreported Entity.

T-cell re-directing bispecific antibodies targeting B-cell maturation antigens have recently entered real-world use in relapsed/refractory multiple myeloma. While no head-to-head comparison has been done, they have generally been observed to have lower-grade toxicities compared with their chimeric antigen receptor T-cell (CAR-T) counterparts. However, in our real-world, single-institution experience, we have encountered two patients receiving teclistamab who experienced high-grade and refractory immune effector cell-associated neurotoxicity syndrome (ICANS) that did not respond to traditional toxicity mitigation strategies of high-dose corticosteroids or other immunosuppressive therapies. As we increase our use of these novel and vital agents, caution must be warranted.

Disability measurement in Multiple Sclerosis patients 55 years and older: What is the Expanded Disability Status Scale really telling clinicians?

BACKGROUND: The Expanded Disability Status Scale (EDSS) measures disease progression in Multiple Sclerosis (MS). EDSS changes are assumed to be due to worsening MS-related disability. Strict interpretation of this premise may include some normal findings as abnormal, inflating the disability score. Further, determining the cause of neurologic symptoms can be difficult in an older population with comorbid illness and polypharmacy. OBJECTIVE: To examine the association between EDSS, age, comorbidities and polypharmacy. METHODS: 106 people, 55 years and older, with and without MS were administered the EDSS and a validated comorbidity questionnaire. Polypharmacy was also assessed. RESULTS: Median EDSS scores were 6.0 in people with MS and 3.0 in people without MS. No participant in our cohort had an EDSS of 0. Higher EDSS scores were associated with older age and more polypharmacy. Pyramidal and cerebellar functional systems accounted for the largest percentage of unique variance between groups. CONCLUSION: Older individuals with and without MS demonstrated significant disability on the EDSS. These findings indicate that EDSS scores may be partially due to factors other than MS. Our understanding of disease course and disability may benefit from the development of normative EDSS scores to correct for these factors.

Case Report: Expanding the Genetic and Phenotypic Spectrum of Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay.

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a rare neurodegenerative disorder caused by biallelic mutations in the SACS gene. Once thought to be limited to Charlevoix-Saguenay region of Quebec, recent evidence has indicated that this disorder is present worldwide. It is classically characterized by the triad of ataxia, pyramidal involvement, and axonal-demyelinating sensorimotor neuropathy. However, diverse clinical features have been reported to be associated with this disorder. In this report, we present the first Iranian family affected by ARSACS with unique clinical features (mirror movements, hypokinesia/bradykinesia, and rigidity) harboring a novel deletion mutation in the SACS gene. Our findings expand the genetic and phenotypic spectrum of this disorder.

A review of ropinirole prolonged release in Parkinson's disease.

Ropinirole prolonged release is a once-daily, 24-hour formulation of ropinirole, a non-ergot dopamine agonist. It is approved as monotherapy and as an adjunct to levodopa in the treatment of Parkinson's disease (PD). Several potential advantages of ropinirole prolonged release compared to the immediate release formulation include maintaining more consistent dopaminergic activity with steadier plasma levels, increased tolerability, greater compliance from a simpler once-daily dosing regimen and ease in dose titration. In a randomized, double-blind, non-inferiority, crossover study, ropinirole prolonged release was shown to have comparable efficacy and tolerability to immediate release ropinirole in early PD patients, with significantly greater compliance. Subjects were converted overnight between ropinirole formulations without loss of efficacy and with good tolerability. In a randomized, double-blind, placebo-controlled study in advanced PD, daily "off" time was reduced by an average of 2.1 hours with ropinirole prolonged release compared to 0.4 hours with placebo. Patients on ropinirole prolonged release were also more likely to require less daily levodopa. Ropinirole prolonged release is well tolerated with a similar adverse effect profile to other non-ergot dopamine agonists. The most common adverse effects include dyskinesia, nausea, dizziness, hallucinations, somnolence, abdominal pain or discomfort and orthostatic hypotension. Ropinirole prolonged release is a safe and effective treatment option for both early and advanced PD. This manuscript briefly reviews the current pharmacological treatment options for PD and provides a more detailed review of the currently available data regarding ropinirole prolonged release as a treatment option for PD.