Objective: To define the minimum important slowing (MIS) of ALS progression that patients would expect from disease-modifying drug treatment in ALS. Methods: In a survey of ALS patients, the MIS in ALS progression (change in the ALS Functional Rating Scale-Revised, ALSFRS-R) was assessed by asking: "At what point of slowing of ALS, as determined by the ALSFRS-R, do you consider a drug to be important?" Data were collected during clinic visits or remotely via the ALS App. Participants were differentiated in the prognostic groups of slower (<0.5), intermediate (≥0.5 and ≤1.0), or faster (>1.0) ALS progression (ALSPR; ALSFRS-R/month). Results: Of 522 participants (ALS App, n = 397; clinic, n = 125), 395 (75.7%) completed the survey, while 127 (24.3%) selected the option "cannot estimate". The distribution of MIS was as follows: modest slowing of ALS progression (5% and 10% slowing, n = 146 patients, 36.9%), moderate slowing (20%, 30%, and 40% slowing, n = 135, 34.2%), and major slowing (≥50% slowing, n = 114, 28.9%). Median MIS was 20% (IQR 10-50%). Patients with faster ALSPR more frequently assessed a major slowing as the MIS (n = 18, 36.0%) compared to those with slower ALSPR (n = 54, 25.2%). Conclusion: A considerable number of participants viewed a modest slowing in ALS progression as the MIS, followed closely by preferences for moderate and major slowing. Expectations varied according to patients' individual ALS progression. These insights may inform the design of future clinical trials in ALS. Study limitations include potential selection and response biases, as well as the predominantly remote digital assessment.

In genetic amyotrophic lateral sclerosis (ALS), the clinical phenotypes, disease progression and neurofilament light chain (NfL) levels are incompletely characterized. In a total cohort of 1988 ALS patients, a subcohort of genetic ALS linked to C9orf72 (n = 137), SOD1 (n = 54), TARDBP (n = 27), and FUS (n = 19) was investigated. The phenotypes of onset region, propagation and motor neuron involvement were analyzed according to the OPM classification. Serum NfL (sNfL) was measured and related to ALS progression (ALSPR, monthly change of ALS Functional Rating Scale–Revised). To quantify NfL elevation relative to ALSPR, the logNfL(index), the log-transformed ratio of sNfL to ALSPR was calculated. C9orf72-associated ALS showed frequent bulbar onset (n = 42.6

OBJECTIVE:To investigate self-assessment of the amyotrophic lateral sclerosis functional rating scale-revised (ALSFRS-R) using the patient's smartphone and to analyze non-inferiority to clinic assessment. METHODS:In an observational study, ALSFRS-R data being remotely collected on a mobile application (App-ALSFRS-R) were compared to ALSFRS-R captured during clinic visits (clinic-ALSFRS-R). ALS progression rate (ALSPR)-as calculated by the monthly decline of ALSFRS-R-and its intrasubject variability (ALSPR-ISV) between ratings were used to compare both cohorts. To investigate non-inferiority of App-ALSFRS-R data, a non-inferiority margin was determined. RESULTS:A total of 691 ALS patients using the ALS-App and 1895 patients with clinic assessments were included. Clinical characteristics for the App-ALSFRS-R and clinic-ALSFRS-R cohorts were as follows: Mean age 60.45 (SD 10.43) and 63.69 (SD 11.30) years (p < 0.001), disease duration 38.7 (SD 37.68) and 56.75 (SD 54.34) months (p < 0.001) and ALSPR 0.72 and 0.59 (p < 0.001), respectively. A paired sample analysis of ALSPR-ISV was applicable for 398 patients with clinic as well as app assessments and did not show a significant difference (IQR 0.12 [CI 0.11, 0.14] vs 0.12 [CI 0.11, 0.14], p = 0.24; Cohen's d = 0.06). CI of IQR for App-ALSFRS-R was below the predefined non-inferiority margin of 0.15 IQR, demonstrating non-inferiority. CONCLUSIONS:Patients using a mobile application for remote digital self-assessment of the ALSFRS-R revealed younger age, earlier disease course, and faster ALS progression. The finding of non-inferiority of App-ALSFRS-R assessments underscores, that data collection using the ALS-App on the patient's smartphone can serve as additional source of ALSFRS-R in ALS research and clinical practice.

BACKGROUND:In amyotrophic lateral sclerosis (ALS), dextromethorphan/quinidine (DMQ) has been reported to reduce bulbar symptoms, including dysarthria and dysphagia. However, data on patients' perceptions of DMQ treatment are limited. METHODS:Data on DMQ treatment were collected from 1065 ALS patients treated at 13 ALS centers between 10-2015 and 06-2025. Patient-reported outcome measures (PROM) of 179 participants were remotely assessed via the "ALS App". PROM included the self-explanatory version of the ALS Functional Rating Scale (ALSFRS-R-SE), the Net Promoter Score (NPS); and Treatment Satisfaction Questionnaire for Medication (TSQM-9). RESULTS:Mean disease duration was 29.3 months (SD 38.1). ALS progression before treatment was 0.82 points/month (ALSFRS-R). Mean DMQ treatment duration was 8.4 months (SD 10.8), including 35.2% (n = 374) of shorter (<3 months), 35.3% (n = 375) of longer (3-9 months), and 29.5% (n = 313) of very long DMQ treatment (>9 months). Patients' recommendation (n = 178) was positive (NPS: +23) with higher scores after very long DMQ treatment (NPS +37) compared to longer (NPS +15) and shorter treatment (NPS +7.5), respectively. TSQM-9 scores (n = 163) demonstrated high satisfaction for effectiveness 60.0 (SD 25.9), convenience 73.8 (SD 18.2), and global satisfaction 63.4 (SD 29.8). INTERPRETATION:The positive perception in PROM underscores the value of DMQ as an individualized treatment option for bulbar symptoms in ALS. However, shortage of clinical data, online assessment, and selection biases are among the limitations of this study that need to be addressed in further investigations.

Einleitung: Bei Patienten mit adulter 5q-SMA, die eine Risdiplam-Behandlung erhalten, wurden klinische Charakteristika, Behandlungsziele sowie Therapieerfahrungen systematisch erfasst.

In patients with amyotrophic lateral sclerosis (ALS), mechanical insufflation-exsufflation (MI-E) addresses cough deficiency to achieve major therapeutic goals: improving costal muscle and joint function, reducing atelectasis through insufflation, and clearing bronchial secretions via exsufflation. Despite its perceived benefits, there is limited systematic research on MI-E provision, symptom alleviation, or patient satisfaction. The research platform Ambulanzpartner coordinated this longitudinal observational study conducted in 12 German ALS centers from July 2018 to September 2023. Patients were enrolled based on ALS-related cough deficiency requiring MI-E therapy. The study recorded provision, reasons for withholding MI-E, clinical parameters, therapy frequency, subjective cough deficiency, and symptomatic relief. Satisfaction with MI-E therapy was determined by the likelihood of recommendation. Out of 694 ALS patients indicated for MI-E, 527 (75.9%) received the therapy. The primary reason for non-provision was that the patient had died before provision (n = 66 of 167; 39.5%). These patients were significantly more affected as represented by higher progression rates and lower cough peak flows (CPF) at the time of MI-E indication (p < 0.05). Most patients who received MI-E used it daily (n = 290 of 370; 78.4%). Self-assessed cough deficiency correlated with clinical measurements, especially for patients with higher deficits. At follow-up visits, patients reported reduced cough deficiency (p < 0.001). Frequent MI-E use was linked to greater symptom relief and higher likelihood of recommending the therapy. This study highlights the symptomatic and palliative potential of MI-E therapy for ALS patients.

In patients with amyotrophic lateral sclerosis (ALS), mechanical insufflation-exsufflation (MI-E) addresses cough deficiency to achieve major therapeutic goals: improving costal muscle and joint function, reducing atelectasis through insufflation, and clearing bronchial secretions via exsufflation. Despite its perceived benefits, there is limited systematic research on MI-E provision, symptom alleviation, or patient satisfaction. The research platform Ambulanzpartner coordinated this longitudinal observational study conducted in 12 German ALS centers from July 2018 to September 2023. Patients were enrolled based on ALS-related cough deficiency requiring MI-E therapy. The study recorded provision, reasons for withholding MI-E, clinical parameters, therapy frequency, subjective cough deficiency, and symptomatic relief. Satisfaction with MI-E therapy was determined by the likelihood of recommendation. Out of 694 ALS patients indicated for MI-E, 527 (75.9%) received the therapy. The primary reason for non-provision was that the patient had died before provision (n = 66 of 167; 39.5%). These patients were significantly more affected as represented by higher progression rates and lower peak cough flows (PCF) at the time of MI-E indication (p < 0.05). Most patients who received MI-E used it daily (n = 290 of 370; 78.4%). Self-assessed cough deficiency correlated with clinical measurements, especially for patients with higher deficits. At follow-up visits, patients reported reduced cough deficiency (p < 0.001). Frequent MI-E use was linked to greater symptom relief and higher likelihood of recommending the therapy. This study highlights symptomatic and palliative potential of MI-E therapy for ALS patients.

OBJECTIVE:To report the frequency of pathogenic SOD1 gene variants in a screening program in amyotrophic lateral sclerosis (ALS), and the clinical practice of transition to an expanded access program (EAP) of tofersen treatment. METHODS:From October 2021 to February 2024, at 11 ALS centers in Germany genetic testing for SOD1, FUS, TARDBP, and C9orf72 was performed. Patients were offered to opt for notification either about all genetic variants or SOD1 variants relevant for tofersen therapy. The transition to the EAP with tofersen was assessed. RESULTS:1935 patients were screened (94.7% sporadic ALS). 48.8% (n = 928) opted for notification of treatment-relevant information. Genetic variants were found as follows: SOD1 (likely) pathogenic variants (class 4/5) 1.8% (n = 34), variants of unknown significance (class 3) 0.8% (n = 16), FUS (class 4/5) 0.9% (n = 17), TARDBP (class 4/5) 1.3% (n = 25), C9orf72 hexanucleotide repeat expansion 7.0% (n = 135). In SOD1-ALS (encompassing class 3-5 variants, n = 50), 68.0% (n = 34) reported a negative family history. 74.0% (n = 37) of SOD1-ALS patients - which represent 1.9% of all participants of the screening program - were transitioned to tofersen. Median duration from start of genetic testing to treatment was 94 days (57 to 295 days). Eight patients declined treatment whereas five individuals died before initiation of therapy. CONCLUSION:The finding of SOD1 variants in patients with a negative family history underscores the need for a broad genetic screening in ALS. In SOD1-ALS, the treatment option with tofersen was mostly utilized. The wide range in the transition time to tofersen calls for a SOD1-ALS management program.

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.

Background:The introduction of Compulsive Sexual Behavior Disorder (CSBD) into the 11th International Classification of Diseases has raised expectations for better treatment options for CSBD. Furthermore, the treatment demand has increased, particularly for pornography use disorder (PUD), a subtype of CSBD. Presumably due to the easy access to Internet pornography an increasing prevalence of PUD is observed. Consequently, providing tailored and effective treatment is essential. Methods:This article provides an overview of the manualized short-term PornLoS Treatment Program (Pornografienutzungsstörung effektiv behandeln- Leben ohne Suchtdruck; translation: Treating pornography use disorder effectively - life without craving). The program combines 24 individual and 6 group psychotherapy sessions with an interdisciplinary approach by offering a novel treatment framework. This includes, e.g., a mobile app, establishment of self-help groups, and access to other social services such as couple counseling. The cognitive-behavioral treatment program contains interventions addressing psychoeducation, cue exposure, impulse control, cognitive restructuring, emotional regulation, and relapse management.We here also describe the study protocol of an ongoing four-arm randomized controlled trial. The aim is to test two variants of the PornLoS Treatment Program differing with respect to their treatment goal (abstinence or reduced pornography use) against cognitive-behavioral treatment as usual and against a waitlist control group. The primary outcome is the absence of a PUD diagnosis at the end of therapy. The total target sample size will comprise n = 316 patients with PUD across eight study sites. Results:The results will be presented at international conferences and published in a scientific peer-reviewed journal.

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.

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.

Abstract Objective Robotic arms are innovative assistive devices for ALS patients with progressive motor deficits of arms and hands. The objective was to explore the patients´ expectations towards a robotic arm system and to assess the actual experiences after the provision of the device. Methods A prospective observational study was conducted at 9 ALS centers in Germany. ALS-related functional deficits were assessed using the ALS-Functional Rating Scale-revised (ALSFRS-R). Motor deficit of the upper limbs was determined using a subscore of three arm-related items of the ALSFRS-R (items 4–6; range 0–12 points). User expectations before provision (expectation group, n = 85) and user experiences after provision (experience group, n = 14) with the device (JACO Assistive Robotic Device, Kinova, Boisbriand, QC, Canada) were assessed. Results In the total cohort, mean ALSFRS-R subscore for arm function was 1.7 (SD: 2.0, 0–9) demonstrating a severe functional deficit of the upper limbs. In the expectation group (n = 85), the following use cases of the robotic arm have been prioritized: handling objects (89%), close-body movements (88%), pressing buttons (87%), serving drinks (86%), and opening cabinets and doors (85%). In the experience group (n = 14), handling objects (79%), serving drinks (79%), near-body movements (71%), pushing buttons (71%), serving food (64%), and opening doors (64%) were the most frequent used cases. Most patients used the device daily (71.4%, n = 10), and 28.6% (n = 4) several times a week. All patients of the experience group found the device helpful, felt safe while using the device, and were satisfied with its reliability. NPS of the assistive robotic arm revealed 64% "promoters" (strong recommendation), 29% "indifferents" (uncertain recommendation) and 7% "detractors" (no recommendation). Total NPS was + 57 demonstrating strong patient satisfaction. Conclusions Initiation of procurement with a robotic assistive arm was confined to patients with severe functional deficit of the upper limbs. User experience underlined the wide spectrum of use cases of assistive robotic arms in ALS. The positive user experience together with high satisfaction underscore that robotic arm systems serve as a valuable treatment option in ALS patients with severe motor deficits of the arms.

AbstractBackground and aimsFor 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.MethodsFour 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).ResultsThe 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 conclusionsAlthough PUD occurs quite often in Germany, availability of mental health care services for PUD is poor. Specific PUD treatments are urgently needed.