Fatigue is a common symptom in various diseases, including multiple sclerosis (MS). The current standard method to assess fatigue is through questionnaires, which has several shortcomings; questionnaires are subjective, prone to recall bias, and potentially confounded by other symptoms like stress and depression. Thus, there is an unmet medical need to develop objective and reliable methods to evaluate fatigue. Our study seeks to develop an objective and ubiquitous monitoring tool for assessing fatigue. Leveraging a smartphone-based rapid tapping task, we conducted a two-week in-the-wild study with 35 MS patients. We explore the association between tapping derived metrics and perceived fatigue assessed with two standard clinical scales: fatigue severity scale (FSS) and fatigue scale for motor and cognitive function (FSMC). Our novel smartphone-based fatigue metric, mean tapping frequency, objectively ranks perceived fatigue with a mean AUCROC = .76, CI = [.71, .81] according to the FSMC, and a mean AUCROC = .81, CI = [.76, .86] according to the FSS. These results demonstrate that our approach is feasible and valid in uncontrolled environments. In this work, we provide a promising tool for objective fatigue monitoring to be used in clinical trials and routine medical care.

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Background Dysfunction of the autonomic nervous system is common in multiple sclerosis patients, and probably present years before diagnosis, but its role in the disease is poorly understood. Objectives To study the autonomic nervous system in patients with multiple sclerosis using cardiac autonomic regulation measured with a wearable. Methods In a two-week study, we present a method to standardize the measurement of heart rate variability using a wearable sensor that allows the investigation of circadian trends. Using this method, we investigate the relationship of cardiac autonomic dysfunction with clinical hallmarks and subjective burden of fatigue and autonomic symptoms. Results In 55 patients with multiple sclerosis and 24 healthy age- and gender-matched controls, we assessed the cumulative circadian heart-rate variability trend of two weeks. The trend analysis revealed an effect of inflammation ( P = 0.0490, SMD = -0.5466) and progressive neurodegeneration ( P = 0.0016, SMD = 1.1491) on cardiac autonomic function. No association with subjective symptoms could be found. Conclusions Trend-based heart rate variability measured with a wearable provides the opportunity for unobtrusive long-term assessment of autonomic functions in patients with multiple sclerosis. It revealed a general dysregulation in patients with multiple sclerosis.

BackgroundNeurosarcodosis is one of the most frequent differential diagnoses of multiple sclerosis (MS) and requires central nervous system (CNS) biopsy to establish definite diagnosis according to the latest consensus diagnostic criteria. We here analyzed diagnostic values of basic cerebrospinal fluid (CSF) parameters to distinguish neurosarcoidosis from MS without CNS biopsy.MethodsWe retrospectively assessed clinical, radiological and laboratory data of 27 patients with neurosarcoidosis treated at our center and compared following CSF parameters with those of 138 patients with relapsing-remitting MS: CSF white cell count (WCC), CSF/serum albumin quotient (Qalb), intrathecal production of immunoglobulins including oligoclonal bands (OCB), MRZ reaction, defined as a polyspecific intrathecal production of IgG reactive against ≥2 of 3 the viruses measles (M), rubella (R), and zoster (Z) virus, and CSF lactate levels. Additional inflammatory biomarkers in serum and/or CSF such as neopterin, soluble interleukin-2 receptor (sIL-2R) and C-reactive protein (CRP) were assessed.ResultsThere was no significant difference in the frequency of CSF pleocytosis, but a CSF WCC > 30/μl was more frequent in patients with neurosarcoidosis. Compared to MS, patients with neurosarcoidosis showed more frequently an increased Qalb and CSF lactate levels as well as increased serum and CSF levels of sIL-2R, but a lower frequency of intrathecal IgG synthesis and positive MRZ reaction. Positive likelihood ratio (PLR) of single CSF parameters indicating neurosarcoidosis was highest, if (a) CSF WCC was >30/μl (PLR 7.2), (b) Qalb was >10 × 10−3 (PLR 66.4), (c) CSF-specific OCB were absent (PLR 11.5), (d) CSF lactate was elevated (PLR 23.0) or (e) sIL-2R was elevated (PLR>8.0). The combination of (a) one of three following basic CSF parameters, i.e., (a.1.) CSF WCC >30/ul, or (a.2.) QAlb >10 × 10−3, or (a.3.) absence of CSF-specific OCB, and (b) absence of positive MRZ reaction showed the best diagnostic accuracy (sensitivity and specificity each >92%; PLR 12.8 and NLR 0.08).ConclusionCombined evaluation of basic CSF parameters and MRZ reaction is powerful in differentiating neurosarcoidosis from MS, with moderate to severe pleocytosis and QAlb elevation and absence of intrathecal IgG synthesis as useful rule-in parameters and positive MRZ reaction as a rule-out parameter for neurosarcoidosis.