Quantitative Susceptibility MRI to Detect Brain Iron in Amyotrophic Lateral Sclerosis.

Purpose To investigate the whole-brain landscape of iron-related abnormalities in amyotrophic lateral sclerosis (ALS) by using the in vivo MRI technique of quantitative susceptibility mapping (QSM). Materials and Methods For this prospective study, 28 patients with ALS (mean age, 61 years; age range, 43-77 years; 18 men [mean age, 61 years; range, 43-77 years] and 10 women [mean age, 61 years; range, 47-74 years]) recruited between January 17, 2014, and September 4, 2015, and 39 matched control subjects (mean age, 61 years; age range, 39-77 years; 24 men [mean age, 62 years; range, 39-77 years] and 15 women [mean age, 59 years; range, 39-73 years]) were examined by using structural and susceptibility 3.0-T MRI techniques. Group data were cross sectionally compared with family-wise error (FWE) corrections by using voxel-based morphometry (random-field theory), cortical thickness analysis (Monte Carlo simulated), subcortical volumetry (Bonferroni-corrected Wilcoxon rank-sum testing), and QSM analysis (cluster-enhanced whole-brain permutation testing and Bonferroni-corrected rank-sum testing in regions of interest). In patients with ALS, a potential relationship between diffusion and susceptibility measurements in the corticospinal tracts (CSTs) was also examined by using Spearman rank-correlation tests. Results Conventional structural measures failed to identify atrophy in the present cohort (FWE P > .05). However, QSM identified several whole-brain abnormalities (FWE P < .05) in ALS. Regionally, higher susceptibility (expressed as means in parts per million ± standard errors of the mean) was confirmed in the motor cortex (ALS = 0.0188 ± 0.0003, control = 0.0173 ± 0.0003; P < .001), the left substantia nigra (ALS = 0.127 ± 0.004, control = 0.113 ± 0.003; P = .008), the right substantia nigra (ALS = 0.141 ± 0.005, control = 0.120 ± 0.003; P < .001), the globus pallidus (ALS = 0.086 ± 0.003, control = 0.075 ± 0.002; P = .003), and the red nucleus (ALS = 0.115 ± 0.004, control = 0.098 ± 0.003; P < .001). Lower susceptibility was found in CST white matter (ALS = -0.047 ± 0.001, control = -0.043 ± 0.001; P = .01). Nigral and pallidal QSM values were cross correlated in ALS (ρ2 = 0.42, P < .001), a phenomenon visually traceable in many individual patients. QSM in the CST in ALS also correlated with diffusion-tensor metrics in this tract (ρ2 = 0.25, P = .007). Conclusion Whole-brain MRI quantitative susceptibility mapping analysis is sensitive to tissue alterations in amyotrophic lateral sclerosis that may be relevant to pathologic changes. © RSNA, 2018.

Peripheral nerve atrophy together with higher cerebrospinal fluid progranulin indicate axonal damage in amyotrophic lateral sclerosis.

INTRODUCTION: We aimed to investigate whether sonographic peripheral cross-sectional nerve area (CSA) and progranulin (PGRN), a neuritic growth factor, are related to each other and whether they interact to predict clinical and paraclinical measures in amyotrophic lateral sclerosis (ALS). METHODS: We included 55 ALS patients who had forearm median and ulnar nerve CSA, cerebrospinal fluid (CSF) PGRN, and serum PGRN measures available. CSF PGRN was normalized against the CSF / serum albumin ratio (Qalb ). Using age, sex, height, and weight adjusted general linear models, we examined CSA × CSF PGRN interaction effects on various measures. RESULTS: There was a medium-effect size inverse relationship between CSA and CSF PGRN, but not between CSA and serum PGRN. Lower CSA values together with higher CSF PGRN levels were linked to smaller motor amplitudes. DISCUSSION: In ALS, the constellation of peripheral nerve atrophy together with higher CSF PGRN levels indicates pronounced axonal damage. Muscle Nerve 57: 273-278, 2018.

Quantifying disease progression in amyotrophic lateral sclerosis using peripheral nerve sonography.

INTRODUCTION: In this study we investigated whether peripheral nerve sonography could be used as a biomarker to monitor disease progression in amyotrophic lateral sclerosis (ALS). METHODS: In 37 patients, ulnar and median nerve cross-sectional area (CSA) was determined in at least 2 ultrasound sessions; mean follow-up was 14.5 months. Linear mixed-effects models were conducted to analyze time effects on CSA. RESULTS: Ulnar nerve CSA declined significantly at a monthly rate of -0.04 mm(2) (forearm) and -0.05 mm(2) (wrist); the decrease was more pronounced when baseline CSA was greater. To detect a 50% treatment effect on ulnar nerve CSA, 332 patients would need to be entered in a hypothetical randomized, controlled clinical trial. Time had no significant impact on median nerve CSA. CONCLUSIONS: Distal ulnar nerve ultrasound may be a useful biomarker to monitor disease progression in ALS, especially as hypothetical treatment effects on CSA seem to be detectable in manageable cohort sizes. Muscle Nerve 54: 391-397, 2016.

Peripheral nerve ultrasound in amyotrophic lateral sclerosis phenotypes.

INTRODUCTION: In this study we sought to determine the cross-sectional area (CSA) of peripheral nerves in patients with distinct subtypes of amyotrophic lateral sclerosis (ALS). METHODS: Ulnar and median nerve ultrasound was performed in 78 ALS patients [classic, n = 21; upper motor neuron dominant (UMND), n = 14; lower motor neuron dominant (LMND), n = 20; bulbar, n = 15; primary lateral sclerosis (PLS), n = 8] and 18 matched healthy controls. RESULTS: Compared with controls, ALS patients had significant, distally pronounced reductions of ulnar CSA (forearm/wrist level) across all disease groups, except for PLS. Median nerve CSA (forearm/wrist level) did not differ between controls and ALS. CONCLUSION: Ulnar nerve ultrasound in ALS subgroups revealed significant differences in distal CSA values, which suggests it has value as a marker of LMN involvement. Its potential was particularly evident in the UMND and PLS groups, which can be hard to separate clinically, yet their accurate separation has major prognostic implications.

Interaction of physical function, quality of life and depression in Amyotrophic lateral sclerosis: characterization of a large patient cohort.

BACKGROUND: Due to lack of any curative therapy for ALS, symptomatic treatment and maintenance of quality of life (QoL) is very important. We aimed to characterize the affected domains of QoL in ALS patients and to identify factors which are associated with reduced QoL and increased depression. METHODS: 159 ALS patients answered standardized questionnaires (Beck Depression Inventory-II, SF-36 Health Survey questionnaire, revised ALS functional rating scale). Multiple regression analysis was used to identify correlations between clinical features of ALS patients and depression/QoL scores. In addition, QoL data from ALS patients were compared to age-matched reference values representing the German normal population. RESULTS: QoL of ALS patients was reduced in nearly all SF-36-categories. Progression of physical impairment was positively correlated with depression but reduced QoL scores only in items directly related to physical function. However, QoL was considerably influenced by depression, independently from physical impairment. Regarding distinct patient characteristics one of the most interesting findings was that increasing age was correlated with significantly worse QoL results regarding social functioning. CONCLUSIONS: Depressive symptoms had a strong influence on QoL, hence their detection and treatment is of particular importance. Different domains of QoL are differently affected in subgroups of ALS patients. Being aware of these differences can be valuable for both ALS professional and family caregivers and physicians.

Memory deficits in amyotrophic lateral sclerosis are not exclusively caused by executive dysfunction: a comparative neuropsychological study of amnestic mild cognitive impairment.

BACKGROUND: Recent work suggests that ALS and frontotemporal dementia can occur together and share at least in part the same underlying pathophysiology. However, it is unclear at present whether memory deficits in ALS stem from a temporal lobe dysfunction, or are rather driven by frontal executive dysfunction. In this study we sought to investigate the nature of memory deficits by analyzing the neuropsychological performance of 40 ALS patients in comparison to 39 amnestic mild cognitive impairment (aMCI) patients and 40 healthy controls (HC). The neuropsychological battery tested for impairment in executive functions, as well as memory and visuo-spatial skills, the results of which were compared across study groups. In addition, we calculated composite scores for memory (learning, recall, recognition) and executive functions (verbal fluency, cognitive flexibility, working memory). We hypothesized that the nature of memory impairment in ALS will be different from those exhibited by aMCI patients. RESULTS: Patient groups exhibited significant differences in their type of memory deficit, with the ALS group showing impairment only in recognition, whereas aMCI patients showed short and delayed recall performance deficits as well as reduced short-term capacity. Regression analysis revealed a significant impact of executive function on memory performance exclusively for the ALS group, accounting for one fifth of their memory performance. Interestingly, merging all sub scores into a single memory and an executive function score obscured these differences. CONCLUSION: The presented results indicate that the interpretation of neuropsychological scores needs to take the distinct cognitive profiles in ALS and aMCI into consideration. Importantly, the observed memory deficits in ALS were distinctly different from those observed in aMCI and can be explained only to some extent in the context of comorbid (coexisting) executive dysfunction. These findings highlight the qualitative differences in temporal lobe dysfunction between ALS and aMCI patients, and support temporal lobe dysfunction as a mechanism underlying the distinct cognitive impairments observed in ALS.

Lesions along the upper motor neuronal pathway with locked-in features after lightning strike and cardiac arrest: a case-review analysis.

OBJECTIVE: This study describes a case of lesions of the upper motor neuronal pathway with locked-in features after lightning strike and cardiac arrest. DESIGN: A case-review analysis. METHODS: In a 29-year-old male who was hit by a lightning strike during farming activities, cardiopulmonary resuscitation was provided first by co-workers and continued with success by the medical rescue service. After conducting advanced life support under monitoring and therapeutic hypothermia, quadriplegia with facial diplegia was recognized. A review was undertaken detailing the clinical course. RESULTS: MR imaging presented signs consistent with hypoxia-induced damage and diffusion-weighted MR images revealed pronounced damages along the upper motor neuronal pathway. A reactive electroencephalogram pattern, sustained eye movement and the patient communicating via eye-blinking were interpreted as locked-in features. Two weeks after admission the patient was transferred to a neurological rehabilitation centre for further professional care. CONCLUSION: Direct damage of the upper motor neuron pathway due to the current of the lightning should be considered, albeit the relative contribution of hypoxia-induced damage cannot be separated.

Pulmonary aspiration in perioperative medicine.

Perioperative aspiration into the lungs is an infrequent but potentially serious cause of anesthesia-related morbidity and mortality. It is still a leading cause of death from pulmonary complications. Aspiration occurs in approximately three per 10.000 anesthetic procedures with higher incidences in special patient populations and emergency situations. Any patient with symptoms following aspiration that last for more than two hours in the recovery room should be admitted to an intensive care unit for further observation and therapy. This article reviews incidence, morbidity and mortality of perioperative aspiration as well as risk factors and preventive measures. Among preventive measures the use of drugs designed to increase gastric pH, recent developments in supraglottic airway devices and application of rapid sequence induction with cricoid pressure are discussed. Also, international fasting guidelines and clinical management following aspiration are provided.

Efficacy of three IV non-opioid-analgesics on opioid consumption for postoperative pain relief after total thyroidectomy: a randomised, double-blind trial.

OBJECTIVES: In a randomized, double-blind trial, the synergistic action of intravenous parecoxib, metamizol or paracetamol on postoperative piritramide consumption was compared in patients recovering from total thyroidectomy during the first 24 h while evaluating pain intensity and patient satisfaction. METHODS: 120 patients were randomly allocated to four patient groups treated with normal saline and/or one of non-opioid analgesics (parecoxib 40 mg twice daily, metamizol 1 g three times daily, paracetamol 1 g three times daily) in addition to piritramide using the PCA pump. Beginning in the recovery room (PACU), patients were asked every 2 h for 6 hours and afterwards once every 6 h to quantify their pain experience and patient satisfaction while piritramide consumption was recorded. RESULTS: Upon arrival in the PACU piritramide consumption was high and decreased thereafter significantly in all groups (P < 0.05). There were no significant differences between groups in incremental and cumulative piritramide consumption during the investigation. Also, VAS scores were high upon arrival in the PACU and dropped in all groups continuously after surgery: At 2 h and 4 h after surgery they were significantly lower in parecoxib group compared with NaCl (P < 0.01). For overall patient satisfaction, no significant differences were observed. Pain relief scores at 24 h were significantly higher in parecoxib group as compared to metamizol and paracetamol (P < 0.01). Mild PONV was observed frequently in all groups and was treated with metoclopramide. CONCLUSION: There is no clear-cut difference between the non-opioid drugs used, even though parecoxib seems to be superior in regard to VAS scores and piritramide consumption. However, the clinical significance is debatable.

Tracheostomy under jet-ventilation--an alternative approach to ventilating patients undergoing surgically created or percutaneous dilational tracheostomy.

In a prospective observational study we compared the results of 297 elective tracheostomies under jet-ventilation with regard to its complication rate and practicability. Of those, 156 patients underwent surgically created tracheostomy (SCT) and 141 patients percutaneous dilational tracheostomy (PDT). Initially, in 159 patients jet-ventilation was performed using a jet-cannula inserted intratracheally through the cricothyroid membrane. In the remaining 138 patients the jet-ventilator was connected to the endoscopic instrument channel (2.2 mm ID, 4.9 mm OD, 600 mm Length) and ventilation via the fiberoptic bronchoscope (FB-15x, Pentax Europe GmbH, Hamburg) was applied manually. With jet-ventilation, oxygenation was maintained throughout the procedure as long as the tracheal puncture was successful und jet-cannula fixed in place. The bronchoscope-guided gas stream, when compared to jet-cannula inserted intratracheally, offered more space for tracheostomy and safety for the patient. The permanent danger of mishappenings and dislocation involved with the jet-cannula could be avoided, since the bronchoscope was operating on under direct visualization. Under these circumstances, PDT is an acceptable approach to inserting a tracheostomy tube under jet-ventilation via bronchoscope, particularly for the management of difficult airway in critically ill patients.

Differential involvement of forearm muscles in ALS does not relate to sonographic structural nerve alterations.

OBJECTIVE: We aimed to assess whether differential peripheral nerve involvement parallels dissociated forearm muscle weakness in amyotrophic lateral sclerosis (ALS). METHODS: The analysis comprised 41 ALS patients and 18 age-, sex-, height- and weight-matched healthy controls. Strength of finger-extension and -flexion was measured using the Medical Research Council (MRC) scale. Radial, median and ulnar nerve sonographic cross-sectional area (CSA) and echogenicity, expressed by the hypoechoic fraction (HF), were determined. RESULTS: In ALS, finger extensors were significantly weaker than finger flexors. Sonographic evaluation revealed peripheral nerve atrophy, affecting various nerve segments in ALS. HF was unaltered. CONCLUSIONS: This systematic study confirmed a long-observed physical examination finding in ALS - weakness in finger-extension out of proportion to finger-flexion. This phenomenon was not related to any particular sonographic pattern of upper limb peripheral nerve alteration. SIGNIFICANCE: In ALS, dissociated forearm muscle weakness could aid in the disease's diagnosis. Nerve ultrasound did not provide additional information on the differential involvement of finger-extension and finger-flexion strength.

FIG4 variants in central European patients with amyotrophic lateral sclerosis: a whole-exome and targeted sequencing study.

We aimed to identify the genetic cause of the devastating neurodegenerative disease amyotrophic lateral sclerosis (ALS) in a German family with two affected individuals, and to assess the prevalence of variants in the identified risk gene, FIG4, in a central European ALS cohort. Whole-exome sequencing (WES) and an overlapping data analysis strategy were performed in an ALS family with autosomal dominant inheritance and incomplete penetrance. Additionally, 200 central European ALS patients were analyzed using whole-exome or targeted sequencing. All patients were subjected to clinical, electrophysiological, and neuroradiological characterization to explore genotype-phenotype relationships. WES analysis of the ALS family identified the rare heterozygous frameshift variant FIG4:c.759delG, p.(F254Sfs*8) predicted to delete the catalytic domain and active center from the encoded phosphoinositide 5-phosphatase with a key role in endosomal vesicle trafficking. Additionally, novel or rare heterozygous FIG4 missense variants predicted to be deleterious were detected in five sporadic ALS patients revealing an overall FIG4 variant frequency of 3% in our cohort. Four of six variants identified were previously associated with ALS or the motor and sensory neuropathy Charcot-Marie-Tooth disease type 4J (CMT4J), whereas two variants were novel. In FIG4 variant carriers, disease duration was longer and upper motor neuron predominance was significantly more frequent compared with ALS patients without FIG4 variants. Our study provides evidence for FIG4 as an ALS risk gene in a central European cohort, adds new variants to the mutational spectrum, links ALS to CMT4J on a genetic level, and describes a distinctive ALS phenotype for FIG4 variant carriers.

Impaired set-shifting in amyotrophic lateral sclerosis: An event-related potential study of executive function.

OBJECTIVE: Executive dysfunctions in patients suffering from amyotrophic lateral sclerosis (ALS) are often described but poorly understood. Specifically, research on patients' ability to flexibly shift between cognitive sets is still scarce and unsystematic. The present study set out to compensate for this lack by providing an in-depth analysis of ALS-related set-shifting impairments. METHOD: We first present a quantitative overview of the literature revealing that the Wisconsin Card Sorting Test (WCST) is sensitive to set-shifting impairments in ALS. Moreover, we evaluated patients' performance on a computerized task-switching paradigm modeled after the WCST to elucidate the neurocognitive processes underlying their set-shifting impairments. Twenty-one ALS patients and 21 age- and education-matched controls were required to respond to changing task demands while their EEG was being measured. RESULTS: Behavioral results revealed significant set-shifting deficits in patients suffering from ALS. Executive deficits were accompanied by substantial alterations of event-related brain activity. While switch cues elicited a more positive posterior event-related potential (ERP) waveform than repeat cues in healthy controls, ERP amplitudes did not vary as a function of switching demand in ALS patients. Individual differences in posterior switch positivity were reliably associated with patients' performance on neuropsychological tests of executive functioning. CONCLUSIONS: The absence of switch-related ERP modulations appears to be a sensitive indicator of executive deficits in ALS patients. Our results suggest that ALS compromises the frontoparietal brain networks involved in anticipatory set-shifting, rendering patients unable to flexibly adapt to changes in environmental contingencies.

Age and education-matched cut-off scores for the revised German/Swiss-German version of ECAS.

The Edinburgh Cognitive and Behavioural ALS Screen (ECAS) has been developed to assess cognition and behaviour in patients with amyotrophic lateral sclerosis (ALS). Cognitive impairments of ALS-specific and ALS-non-specific functions can be determined using cut-off scores based on performance of healthy subjects. However, detailed analyses show that older healthy subjects perform worse than younger ones, whereas highly-educated individuals perform better than those with lower education levels. As a consequence, this study presents new age and education matched cut-off scores for the revised German/Swiss-German version of the ECAS based on the performance of 86 healthy subjects.

Structural and diffusion imaging versus clinical assessment to monitor amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis is a progressive neurodegenerative disease that affects upper and lower motor neurons. Observational and intervention studies can be tracked using clinical measures such as the revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) but for a complete understanding of disease progression, objective in vivo biomarkers of both central and peripheral motor pathway pathology are highly desirable. The aim of this study was to determine the utility of structural and diffusion imaging as central nervous system biomarkers compared to the standard clinical measure, ALSFRS-R, to track longitudinal evolution using three time-point measurements. N = 34 patients with ALS were scanned and clinically assessed three times at a mean of three month time intervals. The MRI biomarkers were structural T1-weighted volumes for cortical thickness measurement as well as deep grey matter volumetry, voxel-based morphometry and diffusion tensor imaging (DTI). Cortical thickness focused specifically on the precentral gyrus while quantitative DTI biomarkers focused on the corticospinal tracts. The evolution of imaging biomarkers and ALSFRS-R scores over time were analysed using a mixed effects model that accounted for the scanning interval as a fixed effect variable, and, the initial measurements and time from onset as random variables. The mixed effects model showed a significant decrease in the ALSFRS-R score, (p < 0.0001, and an annual rate of change (AROC) of - 7.3 points). Similarly, fractional anisotropy of the corticospinal tract showed a significant decrease (p = 0.009, AROC = - 0.0066) that, in turn, was driven by a significant increase in radial diffusivity combined with a trend to decrease in axial diffusivity. No significant change in cortical thickness of the precentral gyrus was found (p > 0.5). In addition, deep grey matter volumetry and voxel-based morphometry also identified no significant changes. Furthermore, the availability of three time points was able to indicate that there was a linear progression in both clinical and fractional anisotropy measures adding to the validity of these results. The results indicate that DTI is clearly a superior imaging marker compared to atrophy for tracking the evolution of the disease and can act as a central nervous biomarker in longitudinal studies. It remains, however, less sensitive than the ALSFRS-R score for monitoring decline over time.

A new approach using high volume blood patch for prevention of post-dural puncture headache following intrathecal catheter pump exchange.

BACKGROUND: In an observational study, complications of intrathecal catheter pumps necessitating surgical exchange were analyzed. Also the use of a high-volume prophylactic epidural blood patch (EBP) during surgery for preventing post-dural puncture headache (PDPH) with a follow-up for 1 year is described. MATERIALS AND METHODS: In 22 patients with refractory chronic pain of cancer/noncancer origin or severe spasticity, who were receiving intrathecal morphine including adjuvants or baclofen for symptom relief, catheter exchange with or without pump was performed. In patients with documented symptoms of PDPH following initial intrathecal catheter implantation, a prophylactic EBP with a high blood volume was used for PDPH prevention during surgery. Catheters were replaced using 40 mL EBP before entering dural space at a speed of 5mL/min into the epidural space. Patients were asked to quantify pain experience and functional ability. RESULTS: From a sample of 72 patients admitted for catheter exchange with or without pump, 22 patients (33%) (12 male, 10 female) had a history of PDPH following initial implantation. Diagnostic and therapeutic measures occurring with malfunction of intrathecal catheter pump systems were described. Twenty-one patients were successfully treated with prophylactic EBP, while one patient could not be properly evaluated because of intracranial bleeding as the underlying disease. CONCLUSIONS: A new approach using a high-volume prophylactic EBP for preventing PDPH following catheter exchange is presented. The efficacy and safety of this technique for 1 year follow-up have been evaluated and was found to be safe and potentially effective.

Basal ganglia pathology in ALS is associated with neuropsychological deficits.

OBJECTIVES: To evaluate basal ganglia changes along the amyotrophic lateral sclerosis (ALS)-ALS-frontotemporal dementia (FTD) continuum using multiple, complementary imaging techniques. METHODS: Sixty-seven C9orf72-negative patients with ALS and 39 healthy controls were included in a cross-sectional quantitative MRI study. Seven patients with ALS met criteria for comorbid behavioral variant FTD (ALS-FTD), 18 patients met the Strong criteria for cognitive and/or behavioral impairment (ALS-Plus), and 42 patients had no cognitive impairment (ALS-Nci). Volumetric, shape, and density analyses were performed for the thalamus, amygdala, nucleus accumbens, hippocampus, caudate nucleus, pallidum, and putamen. RESULTS: Significant basal ganglia volume differences were identified between the study groups. Shape analysis revealed distinct atrophy patterns in the amygdala in patients with ALS-Nci and in the hippocampus in patients with ALS-Plus in comparison with controls. Patients with ALS-FTD exhibited pathologic changes in the bilateral thalami, putamina, pallida, hippocampi, caudate, and accumbens nuclei in comparison with all other study groups. A preferential vulnerability has been identified within basal ganglia subregions, which connect directly to key cortical sites of ALS pathology. While the anatomical patterns were analogous, the degree of volumetric, shape, and density changes confirmed incremental pathology through the spectrum of ALS-Nci, ALS-Plus, to ALS-FTD. Performance on verbal memory tests correlated with hippocampal volumes, and accumbens nuclei volumes showed a negative correlation with apathy scores. CONCLUSIONS: We demonstrate correlations between basal ganglia measures and structure-specific neuropsychological performance and a gradient of incremental basal ganglia pathology across the ALS-ALS-FTD spectrum, suggesting that the degree of subcortical gray matter pathology in C9orf72-negative ALS is closely associated with neuropsychological changes.

The Edinburgh Cognitive and Behavioural Amyotrophic Lateral Sclerosis Screen: a cross-sectional comparison of established screening tools in a German-Swiss population.

The Edinburgh Cognitive and Behavioural ALS Screen (ECAS) has recently been developed as a fast and easy cognitive screening tool specifically designed for patients with motor impairments in routine clinical use. The German/Swiss-German version of the ECAS was validated in a German-Swiss consortium. One hundred and thirty-six non-demented ALS patients and 160 healthy controls were included in the study. In addition, the Frontal Assessment Battery (FAB), Montreal Cognitive Assessment (MoCA) and Consortium to Establish a Registry for Alzheimer's Disease plus Scale (CERAD plus) were administered to subgroups of patients. Results showed that administration of ECAS was fast (mean 24 min). Similar to the population in the UK version, ALS patients performed significantly worse in the ALS-specific functions (p < 0.001), specifically in the domain of language (p < 0.001), verbal fluency (p = 0.005) and executive functions (p = 0.02), but not for the non-ALS-specific functions. Carers reported behavioural abnormalities in about 30% and psychotic symptoms in 6% of the patients. Compared to ECAS, FAB, MoCA and CERAD were more generic and performance was not adjusted to motor speed. We conclude that the German/Swiss-German version of the ECAS is a fast and easy to administer cognitive screening instrument sensitive for ALS-specific dysfunctions and behaviour change.

Executive Dysfunctions and Event-Related Brain Potentials in Patients with Amyotrophic Lateral Sclerosis.

A growing body of evidence implies psychological disturbances in amyotrophic lateral sclerosis (ALS). Specifically, executive dysfunctions occur in up to 50% of ALS patients. The recently shown presence of cytoplasmic aggregates (TDP-43) in ALS patients and in patients with behavioral variants of frontotemporal dementia suggests that these two disease entities form the extremes of a spectrum. The present study aimed at investigating behavioral and electrophysiological indices of conflict processing in patients with ALS. A non-verbal variant of the flanker task demanded two-choice responses to target stimuli that were surrounded by flanker stimuli which either primed the correct response or the alternative response (the latter case representing the conflict situation). Behavioral performance, event-related potentials (ERP), and lateralized readiness potentials (LRP) were analyzed in 21 ALS patients and 20 controls. In addition, relations between these measures and executive dysfunctions were examined. ALS patients performed the flanker task normally, indicating preserved conflict processing. In similar vein, ERP and LRP indices of conflict processing did not differ between groups. However, ALS patients showed enhanced posterior negative ERP waveform deflections, possibly indicating increased modulation of visual processing by frontoparietal networks in ALS. We also found that the presence of executive dysfunctions was associated with more error-prone behavior and enhanced LRP amplitudes in ALS patients, pointing to a prefrontal pathogenesis of executive dysfunctions and to a potential link between prefrontal and motor cortical functional dysregulation in ALS, respectively.

Percutaneous endoscopic gastrostomy in amyotrophic lateral sclerosis: a prospective observational study.

Weight loss is increasingly considered as a negative prognostic marker in amyotrophic lateral sclerosis (ALS). Despite the critical importance of nutritional issues in ALS, and the common use of percutaneous endoscopic gastrostomy (PEG), there is a general lack of knowledge on peri-interventional treatment, optimal parameters of enteral nutrition, its timing during disease progression and its potential disease-modifying effects in ALS patients. Here we report the results of a multi-center prospective study of percutaneous endoscopic gastrostomy (PEG) in ALS. In this observational clinical trial, 89 ALS patients were prospectively enrolled over a 3-year period and longitudinal data were collected over 18 months. PEG was a safe procedure even in patients with low forced vital capacity, and prophylactic single-shot antibiosis as well as slow increase of caloric nutrition via PEG was beneficial to avoid complications. No signs of refeeding syndrome were observed. High-caloric intake (>1,500 kcal/d) via PEG in patients that lived at least 12 months after PEG insertion was correlated with prolonged survival. Additional oral food intake was not associated with a worse prognosis. Our results suggest that peri-interventional PEG management should include prophylactic single-shot antibiosis, slow increase of caloric intake, and long-term high-caloric nutrition. Although our results indicate that PEG might be more beneficial when applied early, we believe that it can also be performed safely in patients with far advanced disease. Because of its explorative and observational character, most of our results have to be confirmed by a randomized interventional trial.