Assessment of Multiple Aspects of Upper Extremity Function Independent From Ambulation in Patients With Multiple Sclerosis.

BACKGROUND: Upper extremity function (UEF) is often compromised in multiple sclerosis (MS), although its importance is regularly underrecognized relative to ambulation. We explored the concurrent presence of impairment in UEF and ambulation by examining various aspects of UEF across different levels of ambulation. METHODS: The cohort consisted of 247 patients with clinically definite MS or clinically isolated syndrome according to the revised 2010 McDonald criteria. The Nine-Hole Peg Test and the Expanded Disability Status Scale were used to stratify patients into clinically different subgroups. For UEF, cerebellar function (finger-to-nose test), pyramidal function (pronator drift test), and the ability to perform a task of activities of daily living (drinking-from-cup test) were examined. Patient-reported limitations of UEF in daily life were assessed using the Arm Function in Multiple Sclerosis Questionnaire. RESULTS: Patients in more severely impaired ambulation groups displayed poorer performance on all UEF measures. Although most patients had normal to mild (n = 147) or moderate (n = 46) ambulatory impairment, 87.7% exhibited some level of UEF impairment as defined using the Nine-Hole Peg Test. Most patients had mild UEF impairment (n = 174), accounting for the largest proportion in all ambulation groups (51.9%-77.8%). CONCLUSIONS: A distinct pattern of impairment was found for ambulation and multiple aspects of UEF. Independent assessment of multiple aspects of disability may be helpful in treatment decision-making and could support the development of rehabilitation strategies that specifically target UEF impairment.

Improving Detection of Change in Motor Functioning in Multiple Sclerosis Using Video-Assisted Composite Measures.

BACKGROUND: Assessing motor functioning is important to monitor the disease course of multiple sclerosis (MS). Video-assisted rating of classic neurologic tests and activities of daily living may improve the detection of changes in motor functioning. We investigated the value of using video-assisted composite measures for the detection of changes in mobility and upper extremity function (UEF). METHODS: Forty-three patients with MS were recorded performing motor function tests before and during treatment with fampridine. Patients were classified as improved or not improved on mobility composite (MOB-COM) and UEF composite (UEF-COM) measures based on neurologists' ratings of the tests. The proportional agreements between the composite measures and the conventional measures-the Timed 25-Foot Walk test (T25FW) and the Nine-Hole Peg Test (NHPT)-were determined and compared with patient-perceived improvement, which was determined using patient-reported ratings of changes in mobility and UEF. RESULTS: Agreement between MOB-COM and T25FW was 79.5%, and agreement between UEF-COM and NHPT was 82.1%. Twenty-six of 39 patients (66.7%) reported mobility improvement; 6 of these reports were confirmed by both T25FW and MOB-COM, 4 were confirmed by T25FW only, and 2 were confirmed by MOB-COM only. For UEF, 13 of 39 patients (33.3%) reported improvement; 3 of these were confirmed by the NHPT and 3 were confirmed by the UEF-COM. CONCLUSIONS: Compared with the conventional NHPT measure, the video-assisted composite measure of UEF detected additional patient-perceived improvement. This was less evident for mobility measures. Video-assisted composite measures may enhance the detection of treatment effects in MS clinical practice and trials.

Autoencoder as a New Method for Maintaining Data Privacy While Analyzing Videos of Patients With Motor Dysfunction: Proof-of-Concept Study.

BACKGROUND: In chronic neurological diseases, especially in multiple sclerosis (MS), clinical assessment of motor dysfunction is crucial to monitor the disease in patients. Traditional scales are not sensitive enough to detect slight changes. Video recordings of patient performance are more accurate and increase the reliability of severity ratings. When these recordings are automated, quantitative disability assessments by machine learning algorithms can be created. Creation of these algorithms involves non-health care professionals, which is a challenge for maintaining data privacy. However, autoencoders can address this issue. OBJECTIVE: The aim of this proof-of-concept study was to test whether coded frame vectors of autoencoders contain relevant information for analyzing videos of the motor performance of patients with MS. METHODS: In this study, 20 pre-rated videos of patients performing the finger-to-nose test were recorded. An autoencoder created encoded frame vectors from the original videos and decoded the videos again. The original and decoded videos were shown to 10 neurologists at an academic MS center in Basel, Switzerland. The neurologists tested whether the 200 videos were human-readable after decoding and rated the severity grade of each original and decoded video according to the Neurostatus-Expanded Disability Status Scale definitions of limb ataxia. Furthermore, the neurologists tested whether ratings were equivalent between the original and decoded videos. RESULTS: In total, 172 of 200 (86.0%) videos were of sufficient quality to be ratable. The intrarater agreement between the original and decoded videos was 0.317 (Cohen weighted kappa). The average difference in the ratings between the original and decoded videos was 0.26, in which the original videos were rated as more severe. The interrater agreement between the original videos was 0.459 and that between the decoded videos was 0.302. The agreement was higher when no deficits or very severe deficits were present. CONCLUSIONS: The vast majority of videos (172/200, 86.0%) decoded by the autoencoder contained clinically relevant information and had fair intrarater agreement with the original videos. Autoencoders are a potential method for enabling the use of patient videos while preserving data privacy, especially when non-health-care professionals are involved.

[Paroxysmal hypothermia in multiple sclerosis]. / Paroxysmale hypothermie bij multiple sclerose.

BACKGROUND: Multiple sclerosis (MS) can be accompanied by paroxysmal symptoms. These are diverse in nature and often not well known. CASE DESCRIPTION: In the emergency department, we repeatedly saw a 49-year-old man with secondary progressive MS with recurrent episodes of hypothermia, loss of consciousness, thrombocytopenia and worsening of pre-existing neurological deficits. In some of these episodes we identified an underlying urinary tract infection, which we treated. After normalization of the body temperature, we observed complete recovery of the clinical signs and platelet count. CONCLUSION: Paroxysmal hypothermia can be a symptom of MS and is accompanied by a change in level of consciousness, increase of neurological deficits and haematological disturbances. Usually, there is full recovery after normalization of the body temperature and treatment of any underlying infections. Early recognition of these recurrent symptoms is important to prevent unnecessary diagnostics and overtreatment.

Disease activity following pregnancy-related discontinuation of natalizumab in MS.

OBJECTIVE: To investigate disease activity and disability progression following pregnancy-related discontinuation of natalizumab (NTZ) in patients with relapsing-remitting MS. METHODS: A retrospective cohort study of clinical and radiologic data in patients who discontinued NTZ for pregnancy-related reasons. RESULTS: Twenty-two pregnancy-related NTZ discontinuations in 17 patients were evaluated. The median time to conception was 3.4 months. Relapses were more frequent in patients in whom conception did not occur within 6 months (p = 0.022). Confirmed disability progression occurred in 27.3% and was associated with time to conception (p < 0.001). CONCLUSIONS: Early conception after NTZ discontinuation is associated with a reduced risk of disease activity and disability progression. Continuation of NTZ treatment until confirmed pregnancy should be considered in patients with previously active MS. However, the advantages of continuing the drug until pregnancy should be balanced against the uncertainties in postnatal outcomes.

Outcome Measures in Clinical Trials for Multiple Sclerosis.

Due to the heterogeneous nature of the disease, it is a challenge to capture disease activity of multiple sclerosis (MS) in a reliable and valid way. Therefore, it can be difficult to assess the true efficacy of interventions in clinical trials. In phase III trials in MS, the traditionally used primary clinical outcome measures are the Expanded Disability Status Scale and the relapse rate. Secondary outcome measures in these trials are the number or volume of T2 hyperintense lesions and gadolinium-enhancing T1 lesions on magnetic resonance imaging (MRI) of the brain. These secondary outcome measures are often primary outcome measures in phase II trials in MS. Despite several limitations, the traditional clinical measures are still the mainstay for assessing treatment efficacy. Newer and potentially valuable outcome measures increasingly used or explored in MS trials are, clinically, the MS Functional Composite and patient-reported outcome measures, and on MRI, brain atrophy and the formation of persisting black holes. Several limitations of these measures have been addressed and further improvements will probably be proposed. Major improvements are the coverage of additional functional domains such as cognitive functioning and assessment of the ability to carry out activities of daily living. The development of multidimensional measures is promising because these measures have the potential to cover the full extent of MS activity and progression. In this review, we provide an overview of the historical background and recent developments of outcome measures in MS trials. We discuss the advantages and limitations of various measures, including newer assessments such as optical coherence tomography, biomarkers in body fluids and the concept of 'no evidence of disease activity'.

Gray matter damage in multiple sclerosis: Impact on clinical symptoms.

Traditionally, multiple sclerosis (MS) is considered to be a disease primarily affecting the white matter (WM). However, the development of some clinical symptoms such as cognitive impairment cannot be fully explained by the severity of WM pathology alone. During the past decades it became clear that gray matter (GM) damage of the brain is also of major importance in patients with MS. Thanks to improved magnetic resonance imaging techniques, the in vivo detection of GM pathology became possible, enabling a better understanding of the manifestation of various clinical symptoms, such as cognitive impairment. Using higher field strengths and specific sequences, detection of cortical lesions was increased. However, despite these improvements, visualization of cortical MS lesions remains difficult (only about 30-50% of histopathologically confirmed lesions can be detected at 7 Tesla magnetic resonance imaging (MRI)). Furthermore, more research is needed to understand the exact interplay of cortical lesions, GM atrophy and WM pathology in the development of clinical symptoms. In this review, we summarize the historical background that preceded current research and provide an overview of the current knowledge on clinical consequences of GM pathology in MS in terms of disability, cognitive impairment and other clinically important signs such as epileptic seizures.

The plantar reflex: additional value of stroking the lateral border of the foot to provoke an upgoing toe sign and the influence of experience.

The aim of this work was to determine the value of stroking the lateral dorsal border of the foot, in addition to stroking the sole in patients with a suspected pyramidal tract lesion. In addition, we studied the differences in interpretation between neurologists, residents, and medical students. We included subjects who had weakness of at least one leg and in whom a pyramidal tract lesion was suspected. After testing muscle power, tone, reflexes, and foot tapping, a decision on the presence of a pyramidal syndrome had to be made by each observer. After stimulating the sole as well as the lateral border of the foot, observers made a decision about the presence of a pyramidal syndrome again. Twenty-two legs of 18 patients were examined. Testing the plantar reflex (according to both methods) led to a change of opinion on the presence of a pyramidal syndrome in 45 of 69 (65 %) observations. On analysis according to level of experience, a change of opinion occurred in 19 (86 %) observations by medical students, 15 (65 %) by residents, and 11 (46 %) by neurologists. On eight occasions, the change was prompted by stimulation of the lateral border; in five of these cases the examiner (three medical students and two residents) found a new pathological response. Consecutively stroking the sole and the lateral border may be of added value, especially for less-experienced physicians. It seems that more-experienced physicians need fewer tests in the physical examination in order to identify a pyramidal syndrome of the leg.

Differences in aneurysm and patient characteristics between cohorts of Finnish and Dutch patients with subarachnoid hemorrhage: time trends between 1986 and 2005.

BACKGROUND AND PURPOSE: The high incidence of aneurysmal subarachnoid hemorrhage (aSAH) in Finland may be related to genetic or environmental factors, which may also influence patient and aneurysm characteristics. We compared these characteristics in 2 cohorts in Finland (Kuopio) and the Netherlands (Utrecht). METHODS: For aSAH patients in Kuopio (n=1786) and Utrecht (n=1788), we compared sex, age at onset, and the sites and number of aneurysms from 1986 to 2005. Five-year time trends were assessed with chi(2) tests (sex distribution and the sites and number of aneurysms) and with 1-way ANOVA (age). RESULTS: The proportion of men in Kuopio (46.1%; 95% CI, 43.8% to 48.4%) was higher than in Utrecht (33.6%, 95% CI, 31.4% to 35.8%) and declined in Kuopio from 50.9% (95% CI, 46.3% to 55.5%) in 1986-1990 to 42.8% (95% CI, 38.0% to 47.6%) in 2001-2005. Mean+/-SD age at onset was 52.4+/-13.3 years in Kuopio and 53.3+/-14.3 years in Utrecht. Both increased similarly over time. The most common aneurysm site in the Kuopio cohort was the middle cerebral artery (33.1%; 95% CI, 30.9% to 35.3%) and in the Utrecht cohort was the anterior communicating artery (38.0%; 95% CI, 35.5% to 40.5%). Multiple aneurysms were more frequent in Kuopio (27.8%; 95% CI, 25.1% to 29.2%) than in Utrecht (14.8%; 95% CI, 13.0% to 16.6%). Sites and proportions of multiple aneurysms did not change during 1986-2005. CONCLUSIONS: The cohorts of aSAH patients differed with respect to age at onset and the number and sites of aneurysms. The decline in the proportion of men in Kuopio coincided with increased smoking and alcohol use in women and decreased smoking in men. The differences in aneurysm characteristics remained stable, which suggests that these factors are less influenced by environmental factors.