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.

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.

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.

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.

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.

Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy of Nonopioid Analgesics on Pain following Arthroscopic Knee Surgery.

Purpose. In a randomized, double-blind trial, the efficacy of nonopioid analgesics on postoperative piritramide consumption was compared for pain relief during the first 24 h in patients recovering from arthroscopic knee surgery. Methods. 120 patients were treated with normal saline and/or one of the nonopioid analgesics (parecoxib, metamizole, paracetamol) in addition to piritramide using the PCA pump. Beginning in the postanesthesia care unit (PACU), patients were asked to quantify their pain experience at rest while piritramide consumption was recorded. Results. Piritramide consumption upon arrival in the PACU was high in all groups. However, cumulative consumption in the parecoxib group was significantly lower than that in the placebo group at 6 and 12 h after surgery. At discharge from the PACU, VAS scores dropped in all groups and were significantly lower in the parecoxib group. In the PACU, satisfaction of the patients was moderate and improved with time after surgery. Conclusions. There was statistically significant opioid-saving effect by administering parecoxib with better VAS scores and satisfaction level compared to placebo. The high pain score in the PACU in all groups immediately after recovering from remifentanil-based anesthesia would be prevented if local anesthetics were administered intra-articularly as part of a multimodal analgesic approach.

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.