Serum neurofilament light chain in distinct phenotypes of amyotrophic lateral sclerosis: A longitudinal, multicenter study.

OBJECTIVE: To assess the performance of serum neurofilament light chain (sNfL) in clinical phenotypes of amyotrophic lateral sclerosis (ALS). METHODS: In 2949 ALS patients at 16 ALS centers in Germany and Austria, clinical characteristics and sNfL were assessed. Phenotypes were differentiated for two anatomical determinants: (1) upper and/or lower motor involvement (typical, typMN; upper/lower motor neuron predominant, UMNp/LMNp; primary lateral sclerosis, PLS) and (2) region of onset and propagation of motor neuron dysfunction (bulbar, limb, flail-arm, flail-leg, thoracic onset). Phenotypes were correlated to sNfL, progression, and survival. RESULTS: Mean sNfL was - compared to typMN (75.7 pg/mL, n = 1791) - significantly lower in LMNp (45.1 pg/mL, n = 413), UMNp (58.7 pg/mL n = 206), and PLS (37.6 pg/mL, n = 84). Also, sNfL significantly differed in the bulbar (92.7 pg/mL, n = 669), limb (64.1 pg/mL, n = 1305), flail-arm (46.4 pg/mL, n = 283), flail-leg (53.6 pg/mL, n = 141), and thoracic (74.5 pg/mL, n = 96) phenotypes. Binary logistic regression analysis showed highest contribution to sNfL elevation for faster progression (odds ratio [OR] 3.24) and for the bulbar onset phenotype (OR 1.94). In contrast, PLS (OR 0.20), LMNp (OR 0.45), and thoracic onset (OR 0.43) showed reduced contributions to sNfL. Longitudinal sNfL (median 12 months, n = 2862) showed minor monthly changes (<0.2%) across all phenotypes. Correlation of sNfL with survival was confirmed (p < 0.001). CONCLUSIONS: This study underscored the correlation of ALS phenotypes - differentiated for motor neuron involvement and region of onset/propagation - with sNfL, progression, and survival. These phenotypes demonstrated a significant effect on sNfL and should be recognized as independent confounders of sNfL analyses in ALS trials and clinical practice.

Appetitive conditioning with pornographic stimuli elicits stronger activation in reward regions than monetary and gaming-related stimuli.

Appetitive conditioning plays an important role in the development and maintenance of pornography-use and gaming disorders. It is assumed that primary and secondary reinforcers are involved in these processes. Despite the common use of pornography and gaming in the general population appetitive conditioning processes in this context are still not well studied. This study aims to compare appetitive conditioning processes using primary (pornographic) and secondary (monetary and gaming-related) rewards as unconditioned stimuli (UCS) in the general population. Additionally, it investigates the conditioning processes with gaming-related stimuli as this type of UCS was not used in previous studies. Thirty-one subjects participated in a differential conditioning procedure in which four geometric symbols were paired with either pornographic, monetary, or gaming-related rewards or with nothing to become conditioned stimuli (CS + porn, CS + game, CS + money, and CS-) in an functional magnetic resonance imaging study. We observed elevated arousal and valence ratings as well as skin conductance responses for each CS+ condition compared to the CS-. On the neural level, we found activations during the presentation of the CS + porn in the bilateral nucleus accumbens, right medial orbitofrontal cortex, and the right ventral anterior cingulate cortex compared to the CS-, but no significant activations during CS + money and CS + game compared to the CS-. These results indicate that different processes emerge depending on whether primary and secondary rewards are presented separately or together in the same experimental paradigm. Additionally, monetary and gaming-related stimuli seem to have a lower appetitive value than pornographic rewards.

Compulsive sexual behavior disorder in an inpatient sample with substance use disorder.

Background: Several studies indicate that compulsive sexual behavior disorder (CSBD) shares core elements with substance use disorder (SUD). These findings support the assumption of common mechanisms in addiction, which may lead to a higher tendency in patients with SUD to have comorbid CSBD. Nevertheless, this relationship between CSBD and SUD is poorly understood to date. Aim: This study aimed to compare the prevalence of CSBD and its subtype pornography use disorder (PUD) between a SUD group and a matched control group. Herein, we aimed to test whether patients with SUD are more likely to have a comorbid CSBD/PUD. We further hypothesized that a higher CSBD/PUD prevalence in patients with SUD is accompanied by more pronounced CSBD- and PUD-related personal characteristics. Methods: We assessed CSBD, PUD, and related personal characteristics in an inpatient SUD sample (N = 92) and a healthy control sample matched by age, gender, and educational level. Outcomes: Primary outcomes were the diagnoses of CSBD/PUD as assessed by questionnaires. CSBD/PUD-related personal characteristics were the early onset of problematic pornography consumption, relationship status as a single person, a high sexual motivation, a high level of time spent watching pornography, and a high degree of problematic pornography consumption (Problematic Pornography Consumption Scale, short version). Results: There was no significant difference between groups regarding CSBD prevalence (SUD sample, 3.3%; control sample, 7.6%) and PUD prevalence (SUD sample, 2.2%; control sample, 6.5%). We found relationship status as a single person and the sexual motivation dimension of importance of sex to be the only CSBD-related personal characteristics that were more pronounced in the SUD sample than the matched control group. Clinical Implications: Results indicate no higher tendency for patients with SUD to develop comorbid CSBD/PUD, yet important vulnerabilities (eg, emotional dysregulation) should be considered when treating addictive disorder to prevent possible symptom displacement. Strengths and Limitations: A strength of the study is that we compared a sample of patients with SUD with a matched control sample and used an instrument based on ICD-11 criteria for CSBD. Possible limitations are significant differences between the groups because of the restrictions in an inpatient clinic that may have influenced responses (eg, roommates) and that the control group was not screened for SUD. Therefore, the results should be interpreted with some caution. Conclusion: We found no evidence of an overcomorbidity of SUD and CSBD/PUD. However, a higher rate of vulnerability factors for CSBD/PUD in the SUD sample might suggest some similarities between SUD and CSBD/PUD.

Two subtypes of compulsive sexual behavior disorder.

Models explaining addictive behaviors such as the Interaction of Person-Affect-Cognition-Execution (I-PACE) model emphasize the importance of reinforcement mechanisms for developing and maintaining these behaviors, including compulsive sexual behavior disorder (CSBD) as well as personal characteristics as vulnerability factors. This study aimed to determine whether there are CSBD subtypes distinguished by reinforcement sensitivity. We hypothesize that one subtype is sensitive to positive reinforcement (C+subtype) and one is sensitive to negative reinforcement (È»-subtype). We calculated a cluster analysis with data from 62 patients with CSBD and tested differences between the identified clusters by t-test. The sample consisted only of men. Cluster variables were: the sensitivity to the Behavioral Inhibition and Approach System (BIS/BAS), the severity of depressive symptoms (BDI-II), the severity of Trait Anxiety (STAI-T), Sexual Sensation Seeking (SSSS), Thrill- and Adventure-Seeking (SSS-V subscale), Disinhibition (SSS-V subscale), Experience Seeking (SSS-V subscale), and Boredom Susceptibility (SSS-V subscale). Between-cluster differences were analyzed for Trait Sexual Motivation (TSMQ) and Sexual Compulsivity (SCS). The results showed a two-cluster solution with cluster 1 representing patients sensitive to negative reinforcement (È»-subtype) and cluster 2 representing patients sensitive to positive reinforcement (C+subtype). No significant difference in symptom severity of Sexual Compulsivity between clusters was found. Cluster 2 showed higher Importance of Sex and a higher motivation to seek sexual encounters than cluster 2. We found a two-cluster solution regarding reinforcement sensitivity in patients with CSBD. This may have clinical implications regarding individual therapy by focusing on the underlying maintenance mechanisms.

On the current psychotherapeutic situation for persons with pornography use disorder in Germany.

Background and aims: For the first time, the ICD-11 provides the diagnosis compulsive sexual behavior disorder (CSBD) that can be assigned for pornography use disorder (PUD). This study aimed to estimate the prevalence of PUD and associated consequences in Germany, to identify the psychotherapy demand among likely PUD (lPUD) cases and the treatment supply in different psychotherapeutic settings, to survey psychotherapists' level of expertise regarding PUD, and to identify predictors for psychotherapy demand. Methods: Four studies were conducted: 1. Online study in the general population (n = 2070; m = 48.9%, f = 50.8%, d = 0.2%), 2. Survey among practicing psychotherapists (n = 983), 3. Survey of psychotherapists in psychotherapeutic outpatient clinics (n = 185), 4. Interviews with psychotherapeutic inpatient clinics (n = 28). Results: The estimated prevalence of lPUD in the online study was 4.7% and men were 6.3 times more often affected than women. Compared to individuals without PUD, individuals with lPUD more often indicated negative consequences in performance-related areas. Among lPUD cases, 51.2% of men and 64.3% of women were interested in a specialized PUD treatment. Psychotherapists reported 1.2%-2.9% of lPUD cases among their patients. 43.2%-61.5% of psychotherapists stated to be poorly informed about PUD. Only 7% of psychotherapeutic inpatient clinics provided specific treatments to patients with PUD. While, among other factors, negative consequences attributed to lPUD were predictive for psychotherapy demand, weekly pornography consumption, subjective well-being, and religious attachment were not. Discussion and conclusions: Although PUD occurs quite often in Germany, availability of mental health care services for PUD is poor. Specific PUD treatments are urgently needed.

Performance of serum neurofilament light chain in a wide spectrum of clinical courses of amyotrophic lateral sclerosis-a cross-sectional multicenter study.

BACKGROUND AND PURPOSE: The objective was to assess the performance of serum neurofilament light chain (sNfL) in amyotrophic lateral sclerosis (ALS) in a wide range of disease courses, in terms of progression, duration and tracheostomy invasive ventilation (TIV). METHODS: A prospective cross-sectional study at 12 ALS centers in Germany was performed. sNfL concentrations were age adjusted using sNfL Z scores expressing the number of standard deviations from the mean of a control reference database and correlated to ALS duration and ALS progression rate (ALS-PR), defined by the decline of the ALS Functional Rating Scale. RESULTS: In the total ALS cohort (n = 1378) the sNfL Z score was elevated (3.04; 2.46-3.43; 99.88th percentile). There was a strong correlation of sNfL Z score with ALS-PR (p < 0.001). In patients with long (5-10 years, n = 167) or very long ALS duration (>10 years, n = 94) the sNfL Z score was significantly lower compared to the typical ALS duration of <5 years (n = 1059) (p < 0.001). Furthermore, in patients with TIV, decreasing sNfL Z scores were found in correlation with TIV duration and ALS-PR (p = 0.002; p < 0.001). CONCLUSIONS: The finding of moderate sNfL elevation in patients with long ALS duration underlined the favorable prognosis of low sNfL. The strong correlation of sNfL Z score with ALS-PR strengthened its value as progression marker in clinical management and research. The lowering of sNfL in correlation with long TIV duration could reflect a reduction either in disease activity or in the neuroaxonal substrate of biomarker formation during the protracted course of ALS.

Memory representation of aversive social experiences in Social Anxiety Disorder.

Aversive social experiences are proposed to be a risk factor for developing Social Anxiety Disorder (SAD). Many patients with SAD report associated daily life symptoms, such as intrusive re-experiencing (e.g., negatively distorted images of oneself), avoidance, alterations in cognitions and mood, as well as hyperarousal, resembling symptom dimensions of Posttraumatic Stress Disorder (PTSD). These PTSD-like symptoms may result from maladaptive processing and representation of the aversive social experiences in memory. Emotional hyperreactivity during memory retrieval of aversive social experiences is another feature of SAD which was found in previous studies. This study aimed to further investigate PTSD-like symptoms and emotional reactivity associated with etiologically relevant aversive social experiences and shed more light on a potential relationship between both. Eighty-five patients with SAD and 85 healthy controls (HC) participated in this cross-sectional study. It comprised an imagination task with self-report and physiological measures to assess emotional reactivity during the cued recall of the aversive social experience and clinical interviews to assess PTSD-like symptoms. We expected increased emotional reactivity and more severe PTSD-like symptoms in response to the aversive social experience in patients with SAD compared to HC, as well as a positive correlation between emotional reactivity and PTSD-like symptoms in patients with SAD. Indeed, patients with SAD showed emotional hyperreactivity (self-report, physiology) during the cued recall of the aversive social experiences, also when compared to two control memory conditions (neutral, negative non-social) and HC. Patients with SAD furthermore reported more severe PTSD-like symptoms compared to HC and intrusive re-experiencing symptoms were positively correlated with distress during imagery of the social aversive event in patients with SAD. These results might point toward a maladaptive representation of aversive social experiences in memory. Similar to PTSD, this maladaptive memory representation might promote the development of PTSD-like symptoms such as intrusive re-experiencing (e.g., in the form of intrusive self-images in patients with SAD), which might finally lead to and maintain symptoms of SAD.

Processing of sensory, painful and vestibular stimuli in the thalamus.

OBJECTIVES: The thalamus plays an important role in the mediation and integration of various stimuli (e.g., somatosensory, pain, and vestibular). Whether a stimulus-specific and topographic organization of the thalamic nuclei exists is still unknown. The aim of our study was to define a functional, in vivo map of multimodal sensory processing within the human thalamus. METHODS: Twenty healthy individuals (10 women, 21-34 years old) participated. Defined sensory stimuli were applied to both hands (innocuous touch, mechanical pain, and heat pain) and the vestibular organ (galvanic stimulation) during 3 T functional MRI. RESULTS: Bilateral thalamic activations could be detected for touch, mechanical pain, and vestibular stimulation within the left medio-dorsal and right anterior thalamus. Heat pain did not lead to thalamic activation at all. Stimuli applied to the left body side resulted in stronger activation patterns. Comparing an early with a late stimulation interval, the mentioned activation patterns were far more pronounced within the early stimulation interval. CONCLUSIONS: The right anterior and ventral-anterior nucleus and the left medio-dorsal nucleus appear to be important for the processing of multimodal sensory information. In addition, galvanic stimulation is processed more laterally compared to mechanical pain. The observed changes in activity within the thalamic nuclei depending on the stimulation interval suggest that the stimuli are processed in a thalamic network rather than a distinct nucleus. In particular, the vestibular network within the thalamus recruits bilateral nuclei, rendering the thalamus an important integrative structure for vestibular function.

Remote digital assessment of amyotrophic lateral sclerosis functional rating scale - a multicenter observational study.

OBJECTIVE: Remote self-assessment of the revised amyotrophic lateral sclerosis functional rating scale (ALSFRS-R) using digital data capture was investigated for its feasibility as an add-on to ALSFRS-R assessments during multidisciplinary clinic visits. METHODS: From August 2017 to December 2021, at 12 ALS centers in Germany, an observational study on remote assessment of the ALSFRS-R was performed. In addition to the assessment of ALSFRS-R during clinic visits, patients were offered a digital self-assessment of the ALSFRS-R - either on a computer or on a mobile application ("ALS-App"). RESULTS: An estimated multicenter cohort of 4,670 ALS patients received care at participating ALS centers. Of these patients, 971 remotely submitted the ALSFRS-R, representing 21% of the multicenter cohort. Of those who opted for remote assessment, 53.7% (n = 521) completed a minimum of 4 ALSFRS-R per year with a mean number of 10.9 assessments per year. Different assessment frequencies were found for patients using a computer (7.9 per year, n = 857) and mobile app (14.6 per year, n = 234). Patients doing remote assessments were more likely to be male and less functionally impaired but many patients with severe disability managed to complete it themselves or with a caregiver (35% of remote ALSFRS-R cohort in King's Stage 4). CONCLUSIONS: In a dedicated ALS center setting remote digital self-assessment of ALSFRS-R can provide substantial data which is complementary and potentially an alternative to clinic assessments and could be used for research purposes and person-level patient management. Addressing barriers relating to patient uptake and adherence are key to its success.

Individual cortisol response to acute stress influences neural processing of sexual cues.

Background and aims: Problematic pornography use can be conceptualized as an impulse control disorder or alternatively as a behavioral addiction. Stress is an important trigger in addiction, but less is known about the neural effect of stress in problematic pornography use. Therefore, we aimed at investigating the effect of stress during the anticipation and viewing of sexually explicit material while considering person characteristics related to potentially being at risk for developing problematic pornography use. Methods: In an fMRI study (n = 157 men, age: mean = 25.46, SD = 4.11) we used a sexual incentive delay task. A social stress test was used to induce stress in half of the participants. Salivary cortisol was repeatedly measured and person characteristics were considered moderating the effects of cortisol response. Results: We found no group differences in the neural responses during the anticipation phase, but a higher reactivity to sexual stimuli in the dACC in the stress group. Acute stress activated a pronounced cortisol response, which positively correlated with neural activations in the reward system (NAcc, dACC) to sexual cues. Further, the individual time spent on pornography use moderated the effect of cortisol in some regions of the reward system (dACC, mOFC). Discussion and conclusions: Our results suggest that acute stress related increases in cortisol can enhance the incentive value of cues announcing sexual stimuli. This might explain why acute stress is considered a trigger of pornography use and relapse and why individual stress response might be a risk factor for developing a problematic pornography use.

Use and subjective experience of the impact of motor-assisted movement exercisers in people with amyotrophic lateral sclerosis: a multicenter observational study.

Motor-assisted movement exercisers (MME) are devices that assist with physical therapy in domestic settings for people living with ALS. This observational cross-sectional study assesses the subjective experience of the therapy and analyzes users' likelihood of recommending treatment with MME. The study was implemented in ten ALS centers between February 2019 and October 2020, and was coordinated by the research platform Ambulanzpartner. Participants assessed symptom severity, documented frequency of MME use and rated the subjective benefits of therapy on a numerical scale (NRS, 0 to 10 points, with 10 being the highest). The Net Promotor Score (NPS) determined the likelihood of a participant recommending MME. Data for 144 participants were analyzed. Weekly MME use ranged from 1 to 4 times for 41% of participants, 5 to 7 times for 42%, and over 7 times for 17%. Particularly positive results were recorded in the following domains: amplification of a sense of achievement (67%), diminution of the feeling of having rigid limbs (63%), diminution of the feeling of being immobile (61%), improvement of general wellbeing (55%) and reduction of muscle stiffness (52%). Participants with more pronounced self-reported muscle weakness were more likely to note a beneficial effect on the preservation and improvement of muscle strength during MME treatment (p < 0.05). Overall, the NPS for MME was high (+ 61). High-frequency MME-assisted treatment (defined as a minimum of five sessions a week) was administered in the majority of participants (59%) in addition to physical therapy. Most patients reported having achieved their individual therapeutic objectives, as evidenced by a high level of satisfaction with MME therapy. The results bolster the justification for extended MME treatment as part of a holistic approach to ALS care.

Social phobic beliefs mediate the relationship between post-event processing regarding the worst socially aversive experience and fear of negative evaluation.

The experience of socially aversive events is proposed to be a critical etiological factor in the development of social anxiety symptoms even though the experience itself is also common among healthy individuals. Rather than the event itself, accompanying factors such as maladaptive processing might be associated with higher levels of social anxiety symptoms. One-hundred-seventy-four individuals participated in this online-survey comprising questionnaires regarding social anxiety symptoms and retrospective reports concerning maladaptive processing of the worst socially aversive event. Structural equation modelling was used to analyze the hypothesized mediation of maladaptive processing and fear of negative evaluation by intrusive re-experiencing and social phobic beliefs. The positive association between retrospectively evaluated maladaptive processing after the worst socially aversive event and fear of negative evaluation was mediated by social phobic beliefs but not by intrusive re-experiencing. These results point towards the relevance of further investigating processing strategies after socially aversive events as a potential influencing factor for SAD development. Trial registration. The trial was registered at the German Clinical Trial Register (DRKS00021502) on June 3rd, 2020. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12144-022-02805-9.

Is There Reduced Hemodynamic Brain Activation in Multiple Sclerosis Even with Undisturbed Cognition?

Cognitive impairments related to changes in deep gray matter and other brain regions occur in up to 70% of people with multiple sclerosis. But do such brain changes also occur in patients without significant cognitive impairment? Eighteen participants with relapsing-remitting multiple sclerosis (RRMS) and fifteen healthy controls participated in this study. Cognitive status, depression, and fatigue were assessed using the Multiple Sclerosis Inventory of Cognition (MUSIC), Beck's Depression Inventory (BDI-II), and the Fatigue Severity Scale (FSS). fMRI was recorded while a participant performed the modified attention network test (ANT). The effects of ANT executive attention network on hemodynamic activation of a priori defined regions of interest, including the hippocampus, anterior cingulate cortex (ACC), thalamus, caudate nucleus, pallidum, and putamen were studied. The individual lesion load was estimated. For fMRI data analysis a general linear model with randomization statistics including threshold-free cluster enhancement as implemented in the FSL software was used. Participants with RRMS showed reduced activation of the executive attention network in the hippocampus, pallidum, and ACC. The thalamus was involved in both group activations but did not differ between groups. In summary, functional changes in the brain can also be demonstrated in RRMS patients without cognitive deficits. The affected brain regions can best be assigned to the attention network for executive control. This association could likely serve as a biological indicator of susceptibility to imminent cognitive impairment in MS.

Acceptance of Enhanced Robotic Assistance Systems in People With Amyotrophic Lateral Sclerosis-Associated Motor Impairment: Observational Online Study.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by a progressive paresis of the extremities and the loss of manual functioning. Due to the severe functional impairment that the disease entails, ALS requires the provision of comprehensive nursing care and a complex set of assistive technology devices. To relieve caregivers and promote autonomy of people with ALS, robotic assistance systems are being developed. This trial aims to evaluate the acceptance of technology, in general, and of robotic arm assistance among people with ALS in order to lay the groundwork for the development of a semiautomatic robotic arm that can be controlled by humans via a multimodal user interface and that will allow users to handle objects and attend to their own bodies. OBJECTIVE: The aim of this study was to perform a systematic analysis of technology commitment and acceptance of robotic assistance systems from the perspective of physically limited people living with ALS. METHODS: The investigation was conducted as a study of a prospective cohort. Participants were only included if they had received a medical diagnosis of ALS. Data collection took place via an online questionnaire on the Ambulanzpartner Soziotechnologie internet platform. Technological commitment was measured using the Neyer short scale. Furthermore, a multidimensional questionnaire was specially developed to analyze participant acceptance of robotic arm assistance: the Acceptance Measure of Robotic Arm Assistance (AMRAA). This questionnaire was accompanied by a video introducing the robot arm. ALS severity was ascertained using the ALS Functional Rating Scale-Extended (ALSFRS-EX). RESULTS: A total of 268 people with ALS participated in the survey. Two-thirds of the participants were male. The overall mean ALS severity score was 42.9 (SD 11.7) points out of 60 on the ALSFRS-EX, with the most relevant restrictions on arms and legs (<60% of normal functioning). Technological commitment ranked high, with the top third scoring 47.2 points out of 60. Younger participants and males showed significantly higher values. The AMRAA score was, again, significantly higher among younger participants. However, the gender difference within the overall cohort was not significant. The more limited the arm functioning of participants according to the ALSFRS-EX subscale, the higher the acceptance rate of robotic assistance. This relationship proved significant. CONCLUSIONS: People with ALS display high technological commitment and feel positive about using technological assistance systems. In our study, younger participants were more open to technology use, in general, and robotic assistance, in particular. Self-appraisal of technology acceptance, competence, and control conviction were generally higher among men. However, any presumed gender difference vanished when users were asked to rate the anticipated usefulness of the technology, in particular the robotic arm. The acceptance was also reflected in users' increased willingness to use a robotic arm as the functionality of their own arms decreased. From the perspective of people with ALS, robotic assistance systems are critical to promoting individual autonomy. Another key consideration in the development of future assistive technologies should be the reduction of caregiver burden. TRIAL REGISTRATION: German Clinical Trials Register DRKS00012803; https://tinyurl.com/w9yzduhd.

Treatment expectations and perception of therapy in adult patients with spinal muscular atrophy receiving nusinersen.

BACKGROUND AND PURPOSE: This was an investigation of treatment expectations and of the perception of therapy in adult patients with 5q-associated spinal muscular atrophy (5q-SMA) receiving nusinersen. METHODS: A prospective, non-interventional observational study of nusinersen treatment in adult 5q-SMA patients was conducted at nine SMA centers in Germany. The functional status, treatment expectations and perceived outcomes were assessed using the Amyotrophic Lateral Sclerosis Functional Rating Scale-extended (ALS-FRS-ex), the Measure Yourself Medical Outcome Profile (MYMOP2), the Treatment Satisfaction Questionnaire for Medication (TSQM-9) and the Net Promoter Score (NPS). RESULTS: In all, 151 patients were included with a median age of 36 years (15-69 years). SMA type 3 (n = 90, 59.6%) prevailed, followed by type 2 (33.8%) and type 1 (6.6%). In SMA types 1-3, median ALS-FRS-ex scores were 25, 33 and 46 (of 60 scale points), respectively. MYMOP2 identified distinct treatment expectations: head verticalization (n = 13), bulbar function (n = 16), arm function (n = 65), respiration (n = 15), trunk function (n = 34), leg function (n = 76) and generalized symptoms (n = 77). Median symptom severity decreased during nusinersen treatment (median observational period 6.1 months, 0.5-16 months) from 3.7 to 3.3 MYMOP2 score points (p < 0.001). The convenience of drug administration was critical (49.7 of 100 TSQM-9 points, SD 22); however, the overall treatment satisfaction was high (74.3, SD 18) and the recommendation rating very positive (NPS +66). CONCLUSIONS: Nusinersen was administered across a broad range of ages, disease durations and motor function deficits. Treatment expectations were highly differentiated and related to SMA type and functional status. Patient-reported outcomes demonstrated a positive perception of nusinersen therapy in adult patients with 5q-SMA.

Alike and different: Associations between orthorexic eating behaviors and exercise addiction.

OBJECTIVE: Symptoms of exercise addiction, a state of compulsively engaging in intense exercise, and orthorexic eating attitudes, the obsession with eating only healthy foods, often occur together. It is assumed that some more general psychological traits underlie this association. Main aim of this report was to examine similarities and differences between orthorexic eating and addictive exercising. METHOD: Six hundred and eight individuals completed an online survey (mean age: 27.5, SD = 11.0 years; 76.5% women) measuring exercise addiction (Exercise Addiction inventory, EAI), orthorexic eating (Düsseldorfer Orthorexie Skala, DOS), personality domains (Big-Five Inventory-10), anxiety and depression (Hospital Anxiety and Depression Scale). RESULTS: Correlations between the DOS and EAI were .43 in women and .62 in men. Structural equation models identified gender-specific as well as behavior-specific psychological correlates. Among women, anxiety correlated with both EAI and DOS. In addition, the DOS correlated with depression and neuroticism while the EAI correlated with conscientiousness. In men, both scales were associated with conscientiousness and the EAI also correlated with extraversion. Clusterability analysis provided no evidence for clusters based on DOS and EAI. DISCUSSION: Present results showed a substantial correlation between addictive exercising and orthorexic eating, however, coefficients were smaller than expected and appeared higher in men. Both behaviors shared few psychological traits (anxiety in women, conscientiousness in men) thereby questioning the assumption of a similar origin. Additionally, gender-specific psychological correlates point to the need for different disease management approaches in women and men.

Non-invasive and tracheostomy invasive ventilation in amyotrophic lateral sclerosis: Utilization and survival rates in a cohort study over 12 years in Germany.

BACKGROUND AND PURPOSE: The aim of this study was to investigate utilization rates, treatment pathways and survival prognosis in patients with amyotrophic lateral sclerosis (ALS) undergoing non-invasive (NIV) and tracheostomy invasive ventilation (TIV) in a real-world setting. METHODS: A prospective cohort study using a single-centre register of 2702 ALS patients (2007 to 2019) was conducted. Utilization of NIV/TIV and survival data were analysed in three cohorts: (i) non-NIV; (ii) NIV (NIV without subsequent TIV); and (iii) TIV (including TIV preceded by NIV). RESULTS: A total of 1720 patients with available data were identified, 72.0% of whom (n = 1238) did not receive ventilation therapy. NIV was performed in 20.8% of patients (n = 358). TIV was performed in 9.5% of patients (n = 164), encompassing both primary TIV (7.2%, n = 124) and TIV with preceding NIV (2.3%, n = 40). TIV was more often utilized without previous NIV (25.7% vs. 8.3% of all ventilated patients), demonstrating that primary TIV was the prevailing pathway for invasive ventilation. The median (range) survival was significantly longer in the NIV cohort (40.8 [37.2-44.3] months) and the TIV cohort (82.1 [68.7-95.6] months) as compared to the non-NIV cohort (33.6 [31.6-35.7] months). CONCLUSIONS: Although NIV represents the standard of care, its utilization rate was low. TIV was mainly started without preceding NIV, suggesting that TIV may not be confined to NIV treatment escalation. However, TIV was pursued in a minority of patients who had previously undergone NIV. The survival benefit observed in the patients with NIV was equal to that reported in a controlled pivotal trial, but the prognosis with TIV is highly variable. The determinants of utilization of NIV/TIV and of survival (bulbar syndrome, availability of ventilation-related home nursing, cultural factors) warrant further investigation.

Real world experience of patients with amyotrophic lateral sclerosis (ALS) in the treatment of spasticity using tetrahydrocannabinol:cannabidiol (THC:CBD).

BACKGROUND: Treatment of spasticity poses a major challenge in amyotrophic lateral sclerosis (ALS) patient management. Delta-9-tetrahydrocannabinol (THC):cannabidiol (CBD) oromucosal spray (THC:CBD), approved for the treatment of spasticity in multiple sclerosis, serves as a complementary off-label treatment option in ALS-related spasticity. However, few structured data are available on THC:CBD in the treatment of spasticity in ALS. METHOD: A retrospective mono-centric cohort study was realised in 32 patients that meet the following criteria: 1) diagnosis of ALS, 2) ALS-related spasticity; 3) treatment with THC:CBD. Spasticity was rated using the Numeric Rating Scale (NRS). Patient's experience with THC:CBD was assessed using the net promoter score (NPS) and treatment satisfaction questionnaire for medication (TSMQ-9) as captured through telephone survey or online assessment. RESULTS: The mean dose THC:CBD were 5.5 daily actuations (range < 1 to 20). Three subgroups of patients were identified: 1) high-dose daily use (≥ 7 daily actuations, 34%, n = 11), 2) low-dose daily use (< 7 daily actuations, 50%, n = 16), 3) infrequent use (< 1 daily actuation, 16%, n = 5). Overall NPS was + 4.9 (values above 0 express a positive recommendation to fellow patients). Remarkably, patients with moderate to severe spasticity (NRS ≥ 4) reported a high recommendation rate (NPS: + 29) in contrast to patients with mild spasticity (NRS < 4; NPS: - 44). For the three main domains of TSQM-9 high mean satisfaction levels were found (maximum value 100): effectiveness 70.5 (±22.3), convenience 76.6 (±23.3) and global satisfaction 75.0 (±24.7). CONCLUSION: THC:CBD is used in a wide dose range suggesting that the drug was applied on the basis of individual patients' needs and preferences. Contributing to this notion, moderate to severe spasticity was associated with an elevated number of daily THC:CBD actuations and stronger recommendation rate (NPS) as compared to patients with mild spasticity. Overall, treatment satisfaction (TSQM-9) was high. The results suggest that THC:CBD may serve as a valuable addition in the spectrum of symptomatic therapy in ALS. However, prospective studies and head-to-head comparisons to other spasticity medications are of interest to further explore the effectiveness of THC:CBD in the management of spasticity, and other ALS-related symptoms.