Olfactory dysfunction after autoimmune encephalitis depending on the antibody type and limbic MRI pathologies.

Objective: Patients' olfactory function after autoimmune encephalitis (AE) involving limbic structures may be impaired. This study aimed to characterize olfactory function in patients after autoimmune encephalitides. Methods: A case-control study was performed including 11 AE patients with antibodies against NMDAR (n = 4), GAD (n = 3), VGKC (n = 3) and antibody-negative AE (n = 1) and a control group of 12 patients with pneumococcal meningo-encephalitis (PC). In subgroup analyses, AE patients with and without NMDAR-antibodies were compared. Olfactory function was assessed using the Sniffin Sticks test and the resulting TDI-score (threshold, discrimination, identification). Involvement of limbic structures was evaluated on imaging data (MRI). Statistical analyses were performed to test for correlations of TDI-score and MRI results. Results: The overall olfactory function of the AE-group and the PC-group was comparable (mean TDI 32.0 [CI 27.3-36.7], 32.3 [CI 28.5-36.0)]. The proportions of hyposmic patients were similar compared to the general population. However, AE patients of the non-NMDAR group had significantly lower TDI-scores (28.9 ± 6,8) than NMDAR patients (37.4 ± 3.5) (p = 0.046) and a significantly lower discrimination capability than the NMDAR patients (9.9 ± 2.0 vs. 14.5 ± 0.6) (p = 0.002). The non-NMDAR patients had significantly more limbic MRI pathologies (6/7) compared to the NMDAR patients (0/4) (p = 0.015). Furthermore, a correlation between limbic MRI pathologies and worse capability of smelling discrimination was found (p = 0.016, r = -0.704, n = 11). Conclusion: Our results indicate that patients with NMDAR autoimmune encephalitis have normal long term olfactory function. However, patients with non-NMDAR autoimmune encephalitis appear to have a persistently impaired olfactory function, probably mediated by encephalitic damage to limbic structures.

Motor-Independent Cognitive Testing in Motor Degenerative Diseases.

Cognitive function is tested through speech- or writing-based neuropsychological instruments. The application and validity of those tests is impeded for patients with diseases that affect speech and hand motor skills. We therefore developed a "motor-free" gaze-controlled version of the Trail Making Test (TMT), including a calibration task to assess gaze accuracy, for completion by means of an eye-tracking computer system (ETCS). This electronic TMT version (eTMT) was evaluated for two paradigmatic "motor-neurodegenerative" diseases, Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS). We screened 146 subjects, of whom 44 were excluded, e.g., because of vision deficits. Patients were dichotomized into subgroups with less (ALS-, PD-) or severe motor affection (ALS+, PD+). All 66 patients and all 36 healthy controls (HC) completed the eTMT. Patients with sufficient hand motor control (ALS-, PD-, PD+) and all HC additionally completed the original paper-pencil-based version of the TMT. Sufficient and comparable gaze fixation accuracy across all groups and the correlations of the eTMT results with the TMT results supported the reliability and validity of the eTMT. PD+ patients made significantly more errors than HC in the eTMT-B. We hereby proved the good applicability of a motor-free cognitive test. Error rates could be a particularly sensitive marker of executive dysfunction.

Sleep Disturbances and Sleep Disordered Breathing Impair Cognitive Performance in Parkinson's Disease.

BACKGROUND: Sleep disturbances and impairment of cognitive function are among the most frequent non-motor symptoms in Parkinson's disease (PD) with negative implications on quality of life of patients and caregivers. Despite the fact that sleep disturbances are a major issue in PD patients, only limited data are available regarding interactions of sleep disturbances and cognitive performance. OBJECTIVE: This post hoc analysis of the RaSPar trial was therefore designed to further elucidate sleep disturbances and their impact on cognition in PD. METHODS: Twenty-six PD patients with sleep disturbances were evaluated thoroughly including assessments of patients' subjective and objective sleep quality by interview, questionnaires, and polysomnography (PSG). Cognitive performance was assessed by Parkinson Neuropsychometric Dementia Assessment (PANDA) and Test of Attentional Performance (TAP), and associations of sleep and cognitive function were evaluated. RESULTS: We did not detect differences in cognitive performance between patients with and without rapid eye movement (REM) sleep behavior disorder (RBD). Instead, cognitive impairment, particularly affecting cognitive domains attention, executive function/working memory, and semantic memory, was associated with impaired PSG-measured sleep quality (e.g., sleep efficiency) and sleep disordered breathing (SDB) (Apnea-Hypopnea Index > 5/h). Global cognitive performance was decreased in patients with SDB (PANDA score 23.2 ± 3.5 vs. 26.9 ± 2.2, P = 0.020, unpaired two-sided t-test). CONCLUSION: Sleep apnea and other sleep disturbances impair cognitive performance in PD and should be evaluated in routine care, and treatment options such as continuous airway pressure therapy should be considered.

Multi-component relaxation in clinically isolated syndrome: Lesion myelination may predict multiple sclerosis conversion.

We performed a longitudinal case-control study on patients with clinically isolated syndrome (CIS) with the aid of quantitative whole-brain myelin imaging. The aim was (1) to parse early myelin decay and to break down its distribution pattern, and (2) to identify an imaging biomarker of the conversion into clinically definite Multiple Sclerosis (MS) based on in vivo measurable changes of myelination. Imaging and clinical data were collected immediately after the onset of first neurological symptoms and follow-up explorations were performed after 3, 6, and, 12 months. The multi-component Driven Equilibrium Single Pulse Observation of T1/T2 (mcDESPOT) was applied to obtain the volume fraction of myelin water (MWF) in different white matter (WM) regions at every time-point. This measure was subjected to further voxel-based analysis with the aid of a comparison of the normal distribution of myelination measures with an age and sex matched healthy control group. Both global and focal relative myelination content measures were retrieved. We found that (1) CIS patients at the first clinical episode suggestive of MS can be discriminated from healthy control WM conditions (p < 0.001) and therewith reproduced our earlier findings in late CIS, (2) that deficient myelination in the CIS group increased in T2 lesion depending on the presence of gadolinium enhancement (p < 0.05), and (3) that independently the CIS T2 lesion relative myelin content provided a risk estimate of the conversion to clinically definite MS (Odds Ratio 2.52). We initially hypothesized that normal appearing WM myelin loss may determine the severity of early disease and the subsequent risk of clinically definite MS development. However, in contrast we found that WM lesion myelin loss was pivotal for MS conversion. Regional myelination measures may thus play an important role in future clinical risk stratification.

Usability of eyetracking computer systems and impact on psychological wellbeing in patients with advanced amyotrophic lateral sclerosis.

Restrictions in communicative abilities are well known in patients with amyotrophic lateral sclerosis (ALS), but only few approaches in terms of evaluation of supportive technologies have been made. We aimed to assess the use and perceived usability of eye-tracking computer devices (ETCS) of severely impacted patients with ALS in an independent, direct manner and relate it to psychological well-being. ETCS enable active communication and social participation in the quadriplegic and anarthric disease state. Therefore, ETCS-based versions of widely used psychosocial questionnaires (ADI-12, SeiQoL-DW, WHO-5) as well as structured questions on communicative functioning and ETCS usage were developed to assess ALS patients, their next of kin and professional caregivers. Eleven patients (ALSFRS-R: 5.3 ± 5.9; ALS duration: 6.5 ± 3.8 years, range 1‒12; 82% invasively ventilated), nine next of kin and 10 professional caregivers could be assessed. Patients reported a mean use of their personal ETCS of 9.1 h per d (range 0.5‒16), with a high user satisfaction, preservation of communicative abilities and subjective indispensability of the ETCS. ETCS use was associated with higher psychological well-being. Next of kin and professional caregivers also nominated some critical aspect, which remains to be clarified. Our results strengthen the evidence that preserved mental autonomy influences psychological well-being in ALS and might even modify disease course and end-of-life-decisions in ALS.

Effects of oxygen-enriched air on cognitive performance during SCUBA-diving - an open-water study.

Backround: Nitrogen narcosis impairs cognitive function, a fact relevant during SCUBA-diving. Oxygen-enriched air (nitrox) became popular in recreational diving, while evidence of its advantages over air is limited. AIM: Compare effects of nitrox28 and air on two psychometric tests. METHODS: In this prospective, double-blind, open-water study, 108 advanced divers (38 females) were randomized to an air or a nitrox-group for a 60-min dive to 24 m salt water. Breathing gas effects on cognitive performance were assessed during the dive using a short- and long-term memory test and a number connection test. RESULTS: Nitrox28 divers made fewer mistakes only on the long-term memory test (p = 0.038). Female divers remembered more items than male divers (p < 0.001). There were no significant differences in the number connection test between the groups. CONCLUSION: Likely owing to the comparatively low N2 reduction and the conservative dive, beneficial nitrox28 effects to diver performance were moderate but could contribute to diving safety.

Eye-tracking-based assessment suggests preserved well-being in locked-in patients.

We assessed quality of life (QoL) and psychological well-being in patients with amyotrophic lateral sclerosis-induced locked-in state and their next of kin in a fully unbiased manner using eye-tracking computer systems. Eleven of 30 screened patients and 9 next of kin completed study procedures. Patients reported good QoL, which appeared to be at the cost of the QoL of their next of kin. Next of kin rated their own or patients' QoL similarly, but they identified different areas as important as compared with patients. Our results are of importance for the discussion of end-of-life decisions and the evaluation of patients' presumed wishes as well as for psychosocial interventions. Ann Neurol 2017;81:310-315.

Improving the assessment of everyday cognitive functioning in patients with epilepsy by means of proxy reports.

OBJECTIVES: The self-report of cognitive deficits by of patients with epilepsy is often poorly correlated with objective test performances but highly related to mood and personality. The aim of this study was to evaluate whether information obtained by close relatives of the patient shows higher correlations with the patients' objective test scores and thereby can be a complementary measure for ensuring a reliable basis for diagnostic decision-making. METHODS: Thirty-four patients and 29 relatives were asked to fill in a questionnaire about everyday cognitive deficits of the patient. All patients completed a neuropsychological test battery comprising measures of memory, attention, and executive functioning and questionnaires on anxiety, depression, and the personality trait neuroticism. RESULTS: Correlations between relatives' reports and patients' test performances were highly significant across all examined domains. By contrast, self-reports of the patients significantly correlated with none of the neuropsychological measures of memory and with only a subset of the objective measures of attention and executive functioning. Regression analyses additionally revealed a strong dependency of the patients' self-assessment on depression, anxiety, and neuroticism (R(2)=0.42). CONCLUSIONS: These results point out the risk of self-reports distorting reality and additionally recommend consulting a close relative of the patient to ensure reliable information about the patient's everyday cognitive functioning.