Left ventricular hypertrabeculation/noncompaction, cardiac phenotype, and neuromuscular disorders.

BACKGROUND: The prognosis of patients with left ventricular hypertrabeculation/noncompaction (LVHT) and its association with neuromuscular disorders (NMDs) is a controversial topic. The aim of this study was to assess whether the prognosis of LVHT patients is dependent on cardiac phenotype and the presence of NMDs. METHODS: Consecutive patients who were diagnosed with LVHT between 1995 and 2016 were included in the study. Cardiac phenotype was classified according to the recommendations of the European Society of Cardiology as: "dilated" if the left ventricular end-diastolic diameter (LVEDD) was >57 mm and left ventricular fractional shortening (FS) was ≤25%; "hypertrophic" if LVEDD was ≤57 mm, FS > 25%, and left ventricular posterior wall (LVPWT) and interventricular septal thickness (IVST) were both >13 mm; "intermediate" if LVEDD was >57 mm and FS > 25% or if LVEDD was ≤57 mm and FS ≤ 25%; and "normal" if LVEDD was ≤57 mm, FS > 25%, and IVST and LVPWT ≤ 13 mm. Therapy was carried out by the treating physicians. RESULTS: LVHT was diagnosed in 273 patients (80 females, 53 ± 16 years). The phenotype was assessed as dilated in 46%, hypertrophic in 8%, intermediate in 17%, and normal in 29% of the patients. Of these patients, 72% underwent neurological examinations, and an NMD was found in 76%. Over a period of 7.4 years (±5.7), 84 patients died and six underwent cardiac transplantation. The highest mortality rate was observed in the dilated and the lowest in the hypertrophic cardiac phenotype groups. Among the dilated phenotype, mortality was higher in patients with than without NMDs. CONCLUSION: Patients with LVHT and dilated cardiac phenotype have a worse prognosis than patients with a hypertrophic or intermediate/normal cardiac phenotype, especially if they suffer from NMDs.

Transcutaneous sacral nerve stimulation for intraoperative verification of internal anal sphincter innervation.

BACKGROUND: The current standard for pelvic intraoperative neuromonitoring (pIONM) is based on intermittent direct nerve stimulation. This study investigated the potential use of transcutaneous sacral nerve stimulation for non-invasive verification of pelvic autonomic nerves. METHODS: A consecutive series of six pigs underwent low anterior rectal resection. For transcutaneous sacral nerve stimulation, an array of ten electrodes (cathodes) was placed over the sacral foramina (S2 to S4). Anodes were applied on the back, right and left thigh, lower abdomen, and intra-anally. Stimulation using the novel method and current standard were performed at different phases of the experiments under electromyography of the autonomic innervated internal anal sphincter (IAS). KEY RESULTS: Transcutaneous stimulation induced increase of IAS activity could be observed in each animal under specific cathode-anode configurations. Out of 300 tested configurations, 18 exhibited a change in the IAS activity correlated with intentional autonomic nerve damage. The damage resulted in a significant decrease of the relative area under the curve of the IAS frequency spectrum (P<.001). Comparison of the IAS spectra under transcutaneous and direct stimulation revealed no significant difference (after rectal resection: median 5.99 µV•Hz vs 7.78 µV•Hz, P=.12; after intentional nerve damage: median -0.27 µV•Hz vs 3.35 µV•Hz, P=.29). CONCLUSIONS AND INFERENCES: Non-invasive selective transcutaneous sacral nerve stimulation could be used for verification of IAS innervation.

Primary central nervous system vasculitis and its mimicking diseases - clinical features, outcome, comorbidities and diagnostic results - A case control study.

OBJECTIVES: To compare clinical features and outcome, imaging characteristics, biopsy results and laboratory findings in a cohort of 69 patients with suspected or diagnosed primary central nervous system vasculitis (PCNSV) in adults; to identify risk factors and predictive features for PCNSV. PATIENTS AND METHODS: We performed a case-control-study including 69 patients referred with suspected PCNSV from whom 25 were confirmed by predetermined diagnostic criteria based on biopsy (72%) or angiography (28%). Forty-four patients turned out to have 15 distinct other diagnoses. Clinical and diagnostic data were compared between PCNSV and Non-PCNSV cohorts. RESULTS: Clinical presentation was not able to discriminate between PCNSV and its differential diagnoses. However, a worse clinical outcome was associated with PCNSV (p=0.005). Biopsy (p=0.004), contrast enhancement (p=0.000) or tumour-like mass lesion (p=0.008) in magnetic resonance imaging (MRI), intrathecal IgG increase (p=0.020), normal Duplex findings of cerebral arteries (p=0.022) and conventional angiography (p 0.010) were able to distinguish between the two cohorts. CONCLUSION: In a cohort of 69 patients with suspected PCNSV, a large number (64%) was misdiagnosed and partly received treatment, since mimicking diseases are very difficult to discriminate. Clinical presentation at manifestation does not help to differentiate PCNSV from its mimicking diseases. MRI and cerebrospinal fluid analysis are unlikely to be normal in PCNSV, though unspecific if pathological. Cerebral angiography and biopsy must complement other diagnostics when establishing the diagnosis in order to avoid misdiagnosis and mistreatment. CLINICAL TRIAL REGISTRATION: German clinical trials register: http://drks-neu.uniklinik-freiburg.de/drks_web/, Unique identifier: DRKS00005347.

Effect of antiseptic irrigation on infection rates of traumatic soft tissue wounds: a longitudinal cohort study.

OBJECTIVE: Acute traumatic wounds are contaminated with bacteria and therefore an infection risk. Antiseptic wound irrigation before surgical intervention is routinely performed for contaminated wounds. However, a broad variety of different irrigation solutions are in use. The aim of this retrospective, non-randomised, controlled longitudinal cohort study was to assess the preventive effect of four different irrigation solutions before surgical treatment, on wound infection in traumatic soft tissue wounds. METHOD: Over a period of three decades, the prophylactic application of wound irrigation was studied in patients with contaminated traumatic wounds requiring surgical treatment, with or without primary wound closure. The main outcome measure was development of wound infection. From 1974-1983, either 0.04 % polihexanide (PHMB), 1 % povidone-iodine (PVP-I), 4 % hydrogen peroxide, or undiluted Ringer's solution were concurrently in use. From 1984-1996, only 0.04 % PHMB or 1 % PVP-I were applied. From 1997, 0.04 % PHMB was used until the end of the study period in 2005. RESULTS: The combined rate for superficial and deep wound infection was 1.7 % in the 0.04 % PHMB group (n=3264), 4.8 % in the 1 % PVP-I group (n=2552), 5.9 % in the Ringer's group (n=645), and 11.7 % in the 4 % hydrogen peroxide group (n=643). Compared with all other treatment arms, PHMB showed the highest efficacy in preventing infection in traumatic soft tissue wounds (p<0.001). However, compared with PVP-I, the difference was only significant for superficial infections. CONCLUSION: The large patient numbers in this study demonstrated a robust superiority of 0.04 % PHMB to prevent infection in traumatic soft tissue wounds. These retrospective results may further provide important information as the basis for power calculations for the urgently needed prospective clinical trials in the evolving field of wound antisepsis.

Brain iron accumulation in Wilson disease: a post mortem 7 Tesla MRI - histopathological study.

AIMS: In Wilson disease (WD), T2/T2*-weighted (T2*w) MRI frequently shows hypointensity in the basal ganglia that is suggestive of paramagnetic deposits. It is currently unknown whether this hypointensity is related to copper or iron deposition. We examined the neuropathological correlates of this MRI pattern, particularly in relation to iron and copper concentrations. METHODS: Brain slices from nine WD and six control cases were investigated using a 7T-MRI system. High-resolution T2*w images were acquired and R2* parametric maps were reconstructed using a multigradient recalled echo sequence. R2* was measured in the globus pallidus (GP) and the putamen. Corresponding histopathological sections containing the lentiform nucleus were examined using Turnbull iron staining, and double staining combining Turnbull with immunohistochemistry for macrophages or astrocytes. Quantitative densitometry of the iron staining as well as copper and iron concentrations were measured in the GP and putamen and correlated with R2* values. RESULTS: T2*w hypointensity in the GP and/or putamen was apparent in WD cases and R2* values correlated with quantitative densitometry of iron staining. In WD, iron and copper concentrations were increased in the putamen compared to controls. R2* was correlated with the iron concentration in the GP and putamen, whereas no correlation was observed for the copper concentration. Patients with more pronounced pathological severity in the putamen displayed increased iron concentration, which correlated with an elevated number of iron-containing macrophages. CONCLUSIONS: T2/T2*w hypointensity observed in vivo in the basal ganglia of WD patients is related to iron rather than copper deposits.

Insight into the mechanism of laquinimod action.

Laquinimod is a small, novel, orally active, well-tolerated molecule that significantly reduced gadolinium-enhancing lesions in patients with multiple sclerosis (MS). Orally administered laquinimod was found to be present within the central nervous system (CNS) in both healthy mice and mice with experimental autoimmune encephalomyelitis (EAE). Laquinimod inhibits development of both acute and chronic EAE. Furthermore, laquinimod minimizes inflammation, demyelination and axonal damage in MOG-induced EAE in mice treated at disease induction and following clinical disease onset. In vitro, laquinimod down-regulates secretion of pro-inflammatory cytokines and enhances production of anti-inflammatory cytokines from peripheral blood mononuclear cells (PBMCs) derived from healthy subjects and untreated relapsing remitting (RR) MS patients. Additionally, patients treated with laquinimod demonstrate up-regulation of brain-derived neurotrophic factor (BDNF) in the serum. In conclusion, treatment with laquinimod is effective in reducing inflammation, demyelination and axonal damage.

Paraganglioma of the filum terminale: review and report of the first case analyzed by CGH.

OBJECTIVE: As a rare tumor paraganglioma of the filum terminale is of diagnostic challenge. A thorough review of all published cases most often reveals a benign course if complete surgically resection is achieved. We report on the first molecular cytogenetic analyses performed on filum termiale paragangliomas. CLINICAL PRESENTATION: A 52-year-old man suffered from low back pain for many years that gradually worsened and was aggravated by sitting and bending. The pain radiated dorsally into both legs. Magnetic resonance imaging (MRI) with and without Gd-DTPA revealed a 12 mm sized, intradural oval mass at the level of L3 with slightly increased T2-signal and a rim of low signal on T2-weighted sequences. The tumor enhanced remarkably after Gd-DTPA. INTERVENTION: The patient underwent a left sided hemilaminectomy of L3. Durotomy revealed a well-delineated, firm and highly vascularized reddish tumor. The proximal terminal filum entered the tumor at the proximal pole and exited its distal pole. Coagulation and dissection of the terminal filum allowed in toto removal of the tumor. DNA was isolated from the formalin-fixed and paraffin-embedded specimen. The tumor was analyzed by comparative genomic hybridization, providing a normal DNA profile without any chromosomal copy number changes. CONCLUSION: The origin of paragangliomas of the CNS and especially of the filum terminale is still unclear. If no complete surgical resection can be achieved, molecular cytogenetic analysis is of additional value to prognostification of paragangliomas of the filum terminale.

Gender differences in the histopathology of MS?

Multiple sclerosis (MS) lesions are histopathologically characterized by inflammation, demyelination/remyelination, axonal damage and gliosis. Animal experimental and in vitro studies suggest that sex hormones influence the immune system and contribute to the increased likelihood in women of developing MS. However, a variety of studies have also shown that remyelination is more marked in female rodents or that female sex hormones are beneficial for myelin repair. To determine whether gender influences the histopathology of MS lesions, we compared the extent of inflammation, axonal damage and remyelination in MS lesions of female and male MS patients. We observed no differences in the composition of inflammatory infiltrates, axonal damage or cortical pathology. Similar numbers of oligodendroglial progenitor cells and mature oligodendrocytes were present in MS lesions. Remyelination is slightly, but not significantly, more extensive in women than men in early MS lesions. The absence of significant differences in lesion pathology between female and male MS patients might be explained by a lack of a gender influence, but also might be due to the limited number of tissue samples available for histopathological analysis.

Short-term adaptation to a simple motor task: a physiological process preserved in multiple sclerosis.

Short-term adaptation indicates the attenuation of the functional MRI (fMRI) response during repeated task execution. It is considered to be a physiological process, but it is unknown whether short-term adaptation changes significantly in patients with brain disorders, such as multiple sclerosis (MS). In order to investigate short-term adaptation during a repeated right-hand tapping task in both controls and in patients with MS, we analyzed the fMRI data collected in a large cohort of controls and MS patients who were recruited into a multi-centre European fMRI study. Four fMRI runs were acquired for each of the 55 controls and 56 MS patients at baseline and 33 controls and 26 MS patients at 1-year follow-up. The externally cued (1 Hz) right hand tapping movement was limited to 3 cm amplitude by using at all sites (7 at baseline and 6 at follow-up) identically manufactured wooden frames. No significant differences in cerebral activation were found between sites. Furthermore, our results showed linear response adaptation (i.e. reduced activation) from run 1 to run 4 (over a 25 minute period) in the primary motor area (contralateral more than ipsilateral), in the supplementary motor area and in the primary sensory cortex, sensory-motor cortex and cerebellum, bilaterally. This linear activation decay was the same in both control and patient groups, did not change between baseline and 1-year follow-up and was not influenced by the modest disease progression observed over 1 year. These findings confirm that the short-term adaptation to a simple motor task is a physiological process which is preserved in MS.

Differentiation block of oligodendroglial progenitor cells as a cause for remyelination failure in chronic multiple sclerosis.

Impaired function/differentiation of progenitor cells might provide an explanation for the limited remyelination observed in the majority of chronic multiple sclerosis lesions. Here, we establish that in the normal adult human CNS, the transcription factors Nkx2.2 and Olig2 are strongly expressed in progenitor cells while mature oligodendrocytes are characterized by low levels of Olig2 or Nkx2.2. In vitro studies confirmed the expression of Olig2 in oligodendroglial progenitor cells and mature oligodendrocytes while astrocytes, microglial cells and neurons were negative for Olig2. In early multiple sclerosis lesions, we found Olig2-positive progenitor cells throughout all lesion stages and in periplaque white matter (PPWM). The number of progenitors in PPWM was significantly increased compared with the white matter from controls. In chronic multiple sclerosis lesions progenitor cells were still present, however, in significantly lower numbers than in early multiple sclerosis lesions. A subpopulation of progenitor cells in early multiple sclerosis lesions and PPWM but not in control cases co-expressed NogoA, a marker of mature oligodendrocytes. The co-expression of these two markers suggested that these cells were maturing oligodendrocytes recently recruited from the progenitor pool. In contrast, in chronic multiple sclerosis lesions maturing progenitors were only rarely present. In summary, we provide evidence that a differentiation block of oligodendroglial progenitors is a major determinant of remyelination failure in chronic multiple sclerosis lesions.

Reproducibility of fMRI in the clinical setting: implications for trial designs.

With expanding potential clinical applications of functional magnetic resonance imaging (fMRI) it is important to test how reliable different measures of fMRI activation are between subjects and sessions and between centres. This study compared variability across 17 patients with multiple sclerosis (MS) and 22 age-matched healthy controls (HC) in 5 European centres performing an fMRI block design with hand tapping. We recruited subjects from sites using 1.5 T scanners from different manufacturers. 5 healthy volunteers also were studied at each of 4 of the centres. We found that reproducibility between runs and sessions for single individuals was consistently much greater than between individuals. There was greater run-to-run variability for MS patients than for HC. Measurements of maximum signal change (MSC) appeared to provide higher reproducibility within individuals and greater sensitivity to differences between individuals than region of interest (ROI) suprathreshold voxel counts. The variability in measurements between centres was not as great as that between individuals. Consistent with these observations, we estimated that power should not be reduced substantially with use of multi-, as opposed to single-, centre study designs with similar numbers of subjects. Multi-centre interventional studies in which fMRI is used as an outcome measure thus appear practical even when implemented in conventional clinical environments.

Impairment of movement-associated brain deactivation in multiple sclerosis: further evidence for a functional pathology of interhemispheric neuronal inhibition.

Motor control demands coordinated excitation and inhibition across distributed brain neuronal networks. Recent work has suggested that multiple sclerosis (MS) may be associated with impairments of neuronal inhibition as part of more general progressive impairments of connectivity. Here, we report results from a prospective, multi-centre fMRI study designed to characterise the changes in patients relative to healthy controls during a simple cued hand movement task. This study was conducted at eight European sites using 1.5 Tesla scanners. Brain deactivation during right hand movement was assessed in 56 right-handed patients with relapsing-remitting or secondary progressive MS without clinically evident hand impairment and in 60 age-matched, healthy subjects. The MS patients showed reduced task-associated deactivation relative to healthy controls in the pre- and postcentral gyri of the ipsilateral hemisphere in the region functionally specialised for hand movement control. We hypothesise that this impairment of deactivation is related to deficits of transcallosal connectivity and GABAergic neurotransmission occurring with the progression of pathology in the MS patients. This study has substantially extended previous observations with a well-powered, multicentre study. The clinical significance of these deactivation changes is still uncertain, but the functional anatomy of the affected region suggests that they could contribute to impairments of motor control.

Relating functional changes during hand movement to clinical parameters in patients with multiple sclerosis in a multi-centre fMRI study.

We performed a prospective multi-centre study using functional magnetic resonance imaging (fMRI) to better characterize the relationships between clinical expression and brain function in patients with multiple sclerosis (MS) at eight European sites (56 MS patients and 60 age-matched, healthy controls). Patients showed greater task-related activation bilaterally in brain regions including the pre- and post-central, inferior and superior frontal, cingulate and superior temporal gyri and insula (P < 0.05, all statistics corrected for multiple comparisons). Both patients and healthy controls showed greater brain activation with increasing age in the ipsilateral pre-central and inferior frontal gyri (P < 0.05). Patients, but not controls, showed greater brain activation in the anterior cingulate gyrus and the bilateral ventral striatum (P < 0.05) with less hand dexterity. An interaction between functional activation changes in MS and age was found. This large fMRI study over a broadly selected MS patient population confirms that movement for patients demands significantly greater cognitive 'resource allocation' and suggests age-related differences in brain responses to the disease. These observations add to evidence that brain functional responses (including potentially adaptive brain plasticity) contribute to modulation of clinical expression of MS pathology and demonstrate the feasibility of a multi-site functional MRI study of MS.

Neocortical neuronal, synaptic, and glial loss in multiple sclerosis.

BACKGROUND: Recent pathologic investigations have shown that neocortical lesions are frequent in multiple sclerosis (MS). Structural MRI has shown that neocortical atrophy occurs early and can be substantial, but the specific substrate for this atrophy has not been defined quantitatively. OBJECTIVE: To investigate cortical thickness as well as neuronal, glial, and synaptic densities in MS. METHODS: We studied brain samples from 22 patients with MS and 17 control subjects. Neocortical lesions and cortical thickness were assessed on sections stained for myelin basic protein. Neuronal, glial, and synaptic densities were measured in type I leukocortical lesions, nonlesional neocortex, and non-MS control cortex. Immunoautoradiography was used to quantify synaptic densities. RESULTS: Neocortical lesions were common in patients with MS. Subpial type III (44%) and leukocortical type I (38%) lesions were more abundant than intracortical type II (18%) lesions. An overall relative neocortical thinning of 10% (p = 0.016) was estimated for the patients. Within the type I lesions, we found evidence for substantial cell (glial, 36%, p = 0.001; neuronal, 10%, p = 0.032) and synaptic (47% decrease in synaptophysin, p = 0.001) loss. Nonlesional neocortex did not show significant relative changes in neuronal, glial, or synaptic density. CONCLUSIONS: Neocortical neuronal and glial degeneration is significant in multiple sclerosis. Synaptic loss was particularly striking in the neocortical lesions, which should make a major independent contribution to the expression of pathology. New therapies should be directed toward limiting this damage.

Pathological differences in acute inflammatory demyelinating diseases of the central nervous system.

This article reviews the different pathological and immunological features of MS, acute variants of MS and acute disseminated encephalomyelitis (ADEM). T-cell-mediated inflammatory reactions are involved in all acute inflammatory diseases of the central nervous system, but the diseases discussed also exhibit distinct immunopathological features. The perivascular infiltrate of T-cells and macrophages seen in ADEM resembles the pathological pattern found in experimental autoimmune encephalomyelitis. In addition, there is evidence that humoral mechanisms play a crucial role in some acute MS lesions, Devics syndrome and Marburgs syndrome. Analysis of acute MS lesions shows many different structural and immunological features, indicating that different mechanisms may be involved in lesion formation. Distinct subtypes of acute lesions exhibit either similarities with T-cell-mediated autoimmune encephalomyelitis or signs of primary oligodendrocyte damage.

[Two-tier screening process (TEOAE/AABR) reduces recall rates in newborn hearing screening]. / Sequenzielles Neugeborenen-Hörscreening (TEOAE/AABR) reduziert Recall-Rate. Erfahrungen in einem Berliner Perinatalzentrum.

BACKGROUND: 1-2/1,000 newborns are affected by connatal permanent hearing impairment. Clinical diagnosis is often delayed. This demands newborn hearing screening (NHS). Some questions regarding the optimal method remain unsolved. METHODS: The newborns in the obstetrical department (low-risk group) are tested by automated transitory evoked otoacustic emissions (TEOAE). TEOAE-fail is followed by automated auditory brainstem response (AABR) examination. All sick newborns admitted to the pediatric department (high-risk group) are primarily tested using AABR. Pathological AABR-testing leads to pedaudiological diagnostic work-up. RESULTS: In the low-risk group, 82 out of 1,584 newborns failed TEOAE-testing (recall 5.18%). Only 5 of these patients failed consecutive AABR examination (recall 0.32%). Permanent hearing loss was finally confirmed in 3 children (0.13%). 10 out of 755 newborns in the high-risk group failed AABR-testing (1.32%). In 6 of these children, hearing loss was confirmed (0.79%). CONCLUSION: A two-tier screening process as described is able to reduce recall rate, overall expenses and parental anxiety.

[Smoking-attributable productivity loss in Germany--a partial sickness cost study based on the human capital potential method]. / Rauchen-attributable Produktivitätsausfallkosten in Deutschland -- eine partielle Krankheitskostenstudie unter Zugrundelegung der Humankapitalmethode.

PURPOSE: Costs of productivity loss for the Federal Republic of Germany attributable to smoking in 1999 was to be determined. METHODS: Mortality and morbidity attributable to smoking is determined by a 0.5 % sample of the smoking behaviour of the German population (microcensus 1999) and the relative mortality risks of smokers (US-American cancer prevention study II). Tobacco smoke-associated cancer illnesses, cardiovascular diseases, respiratory tract diseases and illnesses of children under one year are considered. Calculation of the productivity-relevant consequences of smoking due to morbidity and mortality is effected according to the so-called human potential capital method. RESULTS: In Germany total of 607,393 working years were lost because of smoking in the year 1999. The costs of productivity loss are estimated at 14,480 billion euro. From this 4,525 billion euro are allotted to premature mortality, 5.759 billion euro to permanent disablement and 4.196 billion euro to temporary incapacitation for work. If the costs of productivity loss by smoking are referred to the gross national product (BSP) in the year 1999, an economical damage at a value of 0.74 % of BSPs results. This corresponds to a productivity loss of 379 euro per present or former smoker. The sensitivity analysis manifests that the inclusion of "non-marketable production" results in an immense rise productivity losses attributable to smoking. However, it should be noted that in times of mass unemployment the human capital method which is based on full employment does not measure the actual, but only the potential productivity loss cost. CONCLUSIONS: This partial disease cost study shows that immense economic productivity losses are associated with smoking. This loss of resources can justify a purposeful promotion of studies regarding cost effectiveness of anti-smoking therapeutic measures or preventive measures against smoking. But it should be considered that the use of the human potential capital method results in an overestimation of the actual productivity losses by smoking. In future the costs of productivity losses attributable to smoking should be determined by the friction cost method. With this procedure a more realistic estimation of productivity-relevant costs of smoking is possible.

Mutant prion protein acquires resistance to protease in mouse neuroblastoma cells.

Conversion of the cellular isoform of the prion protein (PrP(C)) into the pathogenic isoform (PrP(Sc)) is thought to be the causative event in prion diseases. Biochemically, PrP(Sc) differs from PrP(C) in its partial resistance to proteinase K (PK). The amino acid sequence AGAAAAGA, comprising residues 112-119 of the murine PrP(C), has been shown to be amyloidogenic and evolutionarily conserved. To assess the effect of mutations at and around this hydrophobic sequence on protease resistance, the sequence was replaced either by alanines or by glycines and, in a third mutant, a large part surrounding this region was removed. The PrP mutant carrying substitutions of glycines for alanines showed PK resistance and aberrant proteolytic processing. Tetracycline-induced expression of this mutant indicated that resistance to protease is acquired concurrent with the synthesis of the protein. These findings indicate that mutations in the central hydrophobic region lead to immediate alterations in PrP structure and processing.

Incidence of recall, nightmares, and hallucinations during analgosedation in intensive care.

OBJECTIVE: To define the incidence of recall and dreams during analgosedation in critically ill patients. DESIGN: Prospective clinical study. SETTING: Anaesthesiological intensive care unit (ICU) in a university hospital. PATIENTS AND PARTICIPANTS: Two hundred and eighty-nine critically ill patients, who either arrived intubated and sedated at the ICU or required intubation, mechanical ventilation, and sedation during their ICU stay. INTERVENTIONS: none. MEASUREMENTS AND RESULTS: The patients were interviewed 48-72 h after discharge from the ICU. By a structured interview they were asked whether they recalled any event before they had regained consciousness at the ICU. Moreover they were asked for dreams. Descriptive statistics: 64.7% of all patients did not recall any event, before they regained consciousness. However, 17% ( n=49) of all patients indicated that they remembered the tracheal tube or being on the ventilator, before they woke up. Some patients (21.1%) reported dreams or dreamlike sensations. Some patients (9.3%) recalled nightmares, while 6.6% reported hallucinations. CONCLUSIONS: Critically ill patients reported a high incidence of recall for unpleasant events, which they thought to have taken place before they regained consciousness. The patients, who stayed longer than 24 h at the ICU, indicated vivid memory for nightmares and hallucinations. Further studies are suggested to evaluate: 1) whether there is an impact of the present findings on outcome; and 2) whether clinical scores for sedation or neurophysiological monitoring help to define the exact time, when recall happens, in order to guide therapeutic intervention.