The Latest Articles on Diagnosis and Assessment of Multiple Sclerosis

Our staff editors continue to share exciting, interesting, and thought-provoking reading material in the recommended articles series.

This week, we would like to share several latest articles on Diagnosis and Assessment of Multiple Sclerosis.

Title: Potential biomaterials and experimental animal models for inventing new drug delivery approaches in the neurodegenerative disorder: Multiple sclerosis
Authors: Dnyandev G. Gadhave, Vrashabh V. Sugandhi, Chandrakant R. Kokare
Type: Review

Abstract:

The tight junction of endothelial cells in the central nervous system (CNS) has an ideal characteristic, acting as a biological barrier that can securely regulate the movement of molecules in the brain. Tightly closed astrocyte cell junctions on blood capillaries are the blood–brain barrier (BBB). This biological barrier prohibits the entry of polar drugs, cells, and ions, which protect the brain from harmful toxins. However, delivering any therapeutic agent to the brain in neurodegenerative disorders (i.e., schizophrenia, multiple sclerosis, etc.) is extremely difficult. Active immune responses such as microglia, astrocytes, and lymphocytes cross the BBB and attack the nerve cells, which causes the demyelination of neurons. Therefore, there is a hindrance in transmitting electrical signals properly, resulting in blindness, paralysis, and neuropsychiatric problems. The main objective of this article is to shed light on the performance of biomaterials, which will help researchers to create nanocarriers that can cross the blood–brain barrier and achieve a therapeutic concentration of drugs in the CNS of patients with multiple sclerosis (MS). The present review focuses on the importance of biomaterials with diagnostic and therapeutic efficacy that can help enhance multiple sclerosis therapeutic potential. Currently, the development of MS in animal models is limited by immune responses, which prevent MS induction in healthy animals. Therefore, this article also showcases animal models currently used for treating MS. A future advance in developing a novel effective strategy for treating MS is now a potential area of research.
Access this article: https://doi.org/10.1016/j.brainres.2023.148674

Title: Multiple Sclerosis Diagnostic Delay and Misdiagnosis
Authors: Marwa Kaisey MD, Andrew J. Solomon MD
Type: Review

Key points:

• Misdiagnosis and delayed diagnosis of MS are both relatively common.

• Delayed diagnosis impacts prognosis by delaying treatment.Misapplication and misunderstanding of the McDonald criteria appear to contribute to MS misdiagnosis

• Comprehensive educational efforts surrounding MS clinical presentations and the correct use of MS diagnostic criteria may prevent misdiagnoses.

Access this article: https://doi.org/10.1016/j.ncl.2023.07.001

Title: Assessment of bidirectional relationships between multiple sclerosis and epilepsy: A two-sample Mendelian randomization study
Authors: Hongzhou Zuo, Li Peng, Wei Li, Yuzhu Wang, Xinyi Du, Xiaoya Zou, Zhaoying Dong, Li Yi, Huimei Yin, Fengying Quan, Oumei Cheng
Type: Research Article
Abstract:

Background and objective
Epidemiological studies indicate that multiple sclerosis (MS) is associated with epilepsy. However, the causality and directionality of this association remain under-elucidated. This study aimed to reveal the causality between MS and epilepsy.

Methods
A two-sample Mendelian randomization (MR) analysis was performed by using summarized statistics derived from large genome-wide association studies of MS and epilepsy. We used the inverse variance weighted method as the primary approach, and then four other MR methods to bidirectionally evaluate the causality of the association between MS and epilepsy. Additional sensitivity analyses were performed to measure the robustness of the findings.

Results
Genetically predicted MS was positively correlated with developing all epilepsy [odds ratio (OR) = 1.027 (1.003–1.051), P  =  0.028] and generalized epilepsy [OR = 1.050 (1.008–1.094), P = 0.019]. In the reverse MR analysis, all epilepsy [OR = 1.310 (1.112–1.543), P = 0.001], generalized epilepsy [OR = 1.173 (1.010–1.363), P = 0.037], and focal epilepsy [OR = 1.264 (1.069–1.494), P  =  0.006] elevated the risk of developing MS. The result remained robust and congruous across all sensitivity analyses conducted.

Conclusions
MS is potentially associated with a higher risk of developing epilepsy. Furthermore, epilepsy may be a causal determinant of MS risk. These findings may further the understanding of the interaction of the two conditions.  
Access this article: https://doi.org/10.1016/j.msard.2023.105148

Title: Validation of the swallowing disturbance questionnaire in people with multiple sclerosis
Authors: Maddalena Sparaco, Elisabetta Maida, Floriana Bile, Renato Vele, Luigi Lavorgna, Giuseppina Miele, Simona Bonavita
Type: Research Article
Abstract:

Background
The DYSPHAGIA IN MULTIPLE SCLEROSIS (DYMUS) questionnaire is the only specific tool developed to screen for dysphagia in people with Multiple Sclerosis (pwMS). However, some limitations of DYMUS could potentially be addressed by the SWALLOWING DISTURBANCE QUESTIONNAIRE (SDQ), which has not yet been validated in pwMS. The objective of this study was to translate and validate the SDQ into the Italian language for use in pwMS to detect swallowing disturbances.

Methods
We translated the SDQ into Italian and adapted it for use in Italian pwMS. PwMS aged > 18 years, assessed for disability using the Expanded Disability Status Scale (EDSS), completed the SDQ and DYMUS questionnaires and performed the 3-OUNCE WATER SWALLOW TEST (WST). Clinical and demographic data were collected for each patient. The Italian version of the SDQ was retested after 30 days.

Results
A total of 84 pwMS were recruited for the study, consisting of 73.8 % women and 48.8 % with a relapsing-remitting form of MS. The mean age of participants was 44.5 years (SD: ±12.46), with a mean disease duration of 17 years (SD: ±10.27), and a median EDSS of 4 (range 1.5–7.5). The Cronbach's alpha for SDQ (to assess internal consistency) was 0.902, which increased to 0.908 after the elimination of item 15, resulting in the SDQ composed of 14 items. ROC analysis demonstrated good accuracy of the 14-item SDQ in pwMS (AUC: 0.811). By dividing the 14-item SDQ score into quartiles, three risk levels for dysphagia were identified: low (score 1–3), intermediate (score 4–8), and high (score ≥9). 14-item SDQ scores significantly correlated with DYMUS (r = 0.820; p<0.0001) and with EDSS (r = 0.541; p<0.0001). PwMS who reported dysphagia had a significantly higher mean 14-item SDQ score (8.27 ± SD 8.15) compared to those without swallowing problems (2.77 ± SD 4.25; p = 0.003). Additionally, pwMS with a positive WST had a significantly higher mean 14-item SDQ score (10.17 ± SD 8.96) than those with a negative WST (2.96 ± SD 3.93; p = 0.02). The Intraclass Correlation Coefficient for the retest, calculated on 48 pwMS in a stable phase of the disease, was 0.91 (95 % CI 0.84–0.95).    

Conclusion
The 14-item SDQ has demonstrated high internal consistency, good accuracy, and reliability in pwMS, making it a readily applicable tool for investigating dysphagia in MS.
Access this article: https://doi.org/10.1016/j.msard.2023.105142

Title: Association between frailty and sleep quality in people living with multiple sclerosis and obesity: An observational cross-sectional study
Authors: Danya Pradeep Kumar, Tobia Zanotto, Julia S. Cozart, Amanda S. Bruce, Christie Befort, Catherine Siengsukon, Robin Shook, Sharon Lynch, Rola Mahmoud, Steve Simon, Paul R. Hibbing, Betty Drees, Joanie Huebner, Taylor Bradish, Jade Robichaud, Jacob J. Sosnoff, Jared M. Bruce
Type: Research Article
Abstract:

Background
A majority of the people with multiple sclerosis (pwMS) experience sleep disturbances. Frailty is also common in pwMS. The geriatric literature strongly suggests that frailty is associated with worse sleep outcomes in community-dwelling older adults, but this association has yet to be explored among pwMS. This study focused on examining the association between frailty and sleep quality in pwMS.

Methods
Seventy-six people with both MS and obesity (mean age: 47.6 ± 10.9 years, 81.6 % female, mean body mass index (BMI): 37.10 ± 5.5 kg/m2, mean Patient Determined Disease Steps (PDDS): 0.82 ± 1.20) were included in this cross-sectional secondary analysis. A comprehensive frailty index (FI) based on 41 health deficits from various health domains was calculated based on standardized procedures. Sleep quality was determined by the Pittsburgh Sleep Quality Index questionnaire (PSQI).

Results
Overall, 67.1 % of the participants were identified as non-frail (FI ≤ 0.25), and 32.9 % were identified as frail (FI > 0.25). A significant correlation was observed between FI scores and global PSQI scores (ρ = 0.43, p < 0.05). Cross-tabulation analyses revealed that frail participants had worse subjective sleep quality, sleep latency, habitual sleep efficiency, sleep disturbances, daytime dysfunction, and higher use of sleep medications compared to non-frail participants (p < 0.05).

Conclusions
The current study identified a significant association between frailty and sleep quality in people with both MS and obesity with minimal disability. These findings underscore the importance of untangling the relationship between frailty and sleep quality in pwMS. These results could lead to a more targeted approach for rehabilitation interventions aiming to improve frailty in MS.
Access this article: https://doi.org/10.1016/j.msard.2023.105154