Neglect and aphasia in the acute phase as predictors of functional outcome 7 years after ischemic stroke.

BACKGROUND AND PURPOSE: Visuospatial inattention (VSI) and language impairment (LI) are often present early after stroke and associations with an unfavorable short-term functional outcome have been reported. The purpose of this study was to investigate whether a screening of VSI and LI as indicators of cortical symptoms early after stroke could predict long-term functional outcomes. METHODS: A consecutive cohort of 375 patients with ischemic stroke was assessed for the occurrence of VSI at a median of 7 days after admission (interquartile range, 1-5 days) using the Star Cancellation Test and for LI (within the first 7 days) with the language item in the Scandinavian Stroke Scale. Seven years later, functional outcomes were assessed by the modified Rankin scale and Frenchay Activities Index in 235 survivors without recurrent stroke. Relationships between baseline predictors and functional outcome at 7 years were analyzed with bivariate correlations and multiple categorical regressions with optimal scaling. RESULTS: The regression model significantly explained variance in the modified Rankin scale (R2 = 0.435, P < 0.001) and identified VSI (P = 0.001) and neurological deficits (P < 0.001; Scandinavian Stroke Scale score without the language item) as the significant independent predictors. The model for Frenchay Activities Index was also significant (R2 = 0.269, P < 0.001) with VSI (P = 0.035) and neurological deficits (P < 0.001) as significant independent predictors. CONCLUSIONS: Visuospatial inattention at acute stroke has an independent impact on long-term functional outcomes. Early recognition may enable targeted rehabilitative interventions.

The prediction of functional dependency by lateralized and non-lateralized neglect in a large prospective stroke sample.

BACKGROUND AND PURPOSE: Lateralized and non-lateralized impairments in visual attention have been identified as important components in patients with visuospatial neglect. This study investigated the course of these two phenomena across time in relation to neurological symptoms and functional outcome in a large consecutive and prospective stroke sample. METHODS: A total of 375 consecutive stroke patients were divided into three groups (lateralized, non-lateralized or no visual inattention) acutely and 3 months post-stroke using the star cancellation test. Neurological impairments, localization of brain damage, asymmetry in clinical symptoms and functional outcome were assessed. Possible group differences were analysed, and stepwise logistic regressions were performed to examine the relative importance of predictors of functional dependency. RESULTS: Participants with acute lateralized inattention differed (P ≤ 0.05) from the other two groups by more often exhibiting severe neurological symptoms, functional dependency and persisting visual inattention. The regression analyses selected acute lateralized inattention as an important and independent predictor of functional dependency following right hemisphere damage, but not following left hemisphere damage. CONCLUSIONS: The results emphasize the prognostic value of lateralized inattention and the importance of separating lateralized and non-lateralized symptoms of visual inattention at the commencement of rehabilitation.

Optimizing in vitro conditions for immunomodulation and expansion of mesenchymal stromal cells.

BACKGROUND AIMS: Mesenchymal stromal cells (MSC) can be expanded in vitro for clinical use and have been evaluated in clinical trials as immunosuppressants and to heal damaged tissues. We investigated the impact of freezing and prolonged storage on cell viability, proliferation and immunosuppression in vitro. METHODS: MSC were expanded from bone marrow (BM) of healthy subjects according to standard protocols in the presence of fetal calf serum (FCS). The immunosuppressive potential of MSC was analyzed in mixed lymphocyte cultures (MLC) and after stimulation with phytohemagglutinin (PHA). RESULTS: Expansion of frozen mononuclear cells (MNC) diminished MSC yield after expansion compared with plating of fresh MNC. MSC derived from frozen MNC were also less immunosuppressive. MSC harvested at various passages after expansion in vivo suppressed lymphocyte proliferation equally. Pooling of MSC from several donors generated higher and more stable suppression in both MLC and after PHA stimulation. After passage 1, plating at lower densities in 20% FCS increased cell expansion of MSC up to 25-fold compared with standard conditions. CONCLUSIONS: MNC should not be frozen prior to MSC expansion. Decreased replating density and increased FCS levels generate higher numbers of MSC. Freezing of ex vivo-expanded MSC for >30 months did not affect cell viability or the ability to suppress lymphocyte proliferation. For effective immunosuppression in vitro MSC should be stored for less than 6 months and pooled from two or three donors.

Neglect assessment as an application of virtual reality.

OBJECTIVE: In this study a cancellation task in a virtual environment was applied to describe the pattern of search and the kinematics of hand movements in eight patients with right hemisphere stroke. METHODS: Four of these patients had visual neglect and four had recovered clinically from initial symptoms of neglect. The performance of the patients was compared with that of a control group consisting of eight subjects with no history of neurological deficits. RESULTS: Patients with neglect as well as patients clinically recovered from neglect showed aberrant search performance in the virtual reality (VR) task, such as mixed search pattern, repeated target pressures and deviating hand movements. The results indicate that in patients with a right hemispheric stroke, this VR application can provide an additional tool for assessment that can identify small variations otherwise not detectable with standard paper-and-pencil tests. CONCLUSION: VR technology seems to be well suited for the assessment of visually guided manual exploration in space.

Transplantation of mesenchymal stem cells to enhance engraftment of hematopoietic stem cells.

Seven patients underwent treatment with mesenchymal stem cells (MSCs), together with allogeneic hematopoietic stem cell transplantation (HSCT). MSCs were given to three patients for graft failure and four patients were included in a pilot study. HSCT donors were three human leukocyte antigen (HLA)-identical siblings, three unrelated donors and one cord blood unit. The conditioning was myeloablative in four patients and reduced in three patients. MSC donors were HLA-identical siblings in three cases and haploidentical in four cases. Neutrophil counts >0.5 x 10(9)/l was reached at a median of 12 (range 10-28) days. Platelet counts >30 x 10(9)/l was achieved at a median of 12 (8-36) days. Acute graft-versus-host disease (GVHD) grade 0-I was seen in five patients. Two patients developed grade II, which in one patient evolved into chronic GVHD. One severe combined immunodeficiency (SCID) patient died of aspergillosis, the others are alive and well. One patient, diagnosed with aplastic anemia had graft failure after her first transplantation and severe Henoch-Schönlein Purpura (HSP). After retransplantation of MSCs and HSCs, she recovered from both the HSP and aplasia. Thus, co-transplantation of MSC resulted in fast engraftment of absolute neutrophil count (ANC) and platelets and 100% donor chimerism, even in three patients regrafted for graft failure/rejection.

Visual neglect and cognitive impairment in elderly patients late after stroke.

OBJECTIVES: To investigate the prevalence of visual neglect and its relationship to cognitive impairment and dementia in elderly stroke patients 20 months after stroke. METHODS: Of 243 stroke patients aged 70-91 years, 149 underwent neuropsychiatric testing, 138 with the Star Cancellation Test for visual neglect. RESULTS: Fifteen per cent (n = 21) had visual neglect, 9% (n = 12) severe and 9% (n = 12) lateralized. Cognitive impairments were twice as common in patients with neglect as in patients without it and threefold more common when the neglect was severe. Neglect was related to apraxia, impaired visual field, and a previous stroke. Severe neglect was related to dementia, amnesia and impaired visual field. CONCLUSIONS: Chronic neglect is common after stroke in elderly patients. So are cognitive impairments, especially in those with neglect. This calls for high alertness to impairments in spatial attention when treating patients with dementia and other cognitive impairments.

Nonlateralized attentional deficits: an important component behind persisting visuospatial neglect?

Simple reaction time was examined in a consecutive series of 60 right hemisphere stroke patients at the postacute stage and at 6 to 7 months poststroke. Reaction times to auditory stimuli were measured within the ipsilesional side of space. Patients showing contralateral neglect in conventional tests of neglect showed significantly increased reaction times at the postacute stage and at the follow-up compared to those not showing neglect and to those in a group of normal controls. The results suggest that a lowered general attentional capacity may constitute a central component behind persistent neglect. An additional analysis of the CT scans of the patients showed that a large lesion including the paraventricular white matter in the temporal lobe was the most important anatomical correlate of persisting slow reactions.

Anatomical and neurological correlates of acute and chronic visuospatial neglect following right hemisphere stroke.

Anatomical and neurological correlates of visuospatial neglect were studied in 53 patients with a CT-documented right hemisphere stroke. Evidence of neglect at the acute stage poststroke was strongly related to large lesions involving the middle temporal gyrus and/or the temporo-parietal paraventricular white matter. Thus, out of 18 patients with evidence of visuospatial neglect at the acute stage, 12 showed a lesion in the middle temporal gyrus and/or the deep temporo-parietal white matter. Among the 35 patients that failed to show visuospatial neglect, only one patient had a lesion within these areas. Comparing those patients who recovered from neglect with those that did not, a high correlation was found between persisting neglect and a lesion involving the paraventricular white matter in the temporal lobe. On the basis of above findings, it was suggested that a simultaneous damage to the cortico-thalamic system for regulation of arousal and to the neural systems mediating visual orienting, is likely to be followed by persisting neglect symptoms.

Concentrations of morphine and morphine metabolites in CSF and plasma during continuous subcutaneous morphine administration in cancer pain patients.

Plasma and cerebrospinal fluid (CSF) steady-state concentrations (Css) of morphine (M) and the main metabolites morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G), were determined by high performance liquid chromatography (HPLC) in 21 cancer patients treated with chronic subcutaneous morphine infusion. There was a moderate, but statistically significant correlation between the daily dose of morphine and the concentrations of morphine, M3G and M6G in CSF. A poorer correlation to concentrations were seen in plasma. The mean +/- SEM CSF/plasma morphine concentration ratio was 0.36 +/- 0.07. In plasma and CSF, the mean steady state concentration of M3G but not M6G substantially exceeded that of morphine where the mean CSF M/M3G/M6G ratio was 1:15:0.5 (molar basis), and the mean plasma ratio was M/M3G/M6G 1:31:3 (molar basis). The mean M3G and M6G concentrations in CSF were approximately 8 and 10% of those found in plasma, but there was a wide interindividual variation. Plasma concentrations of both morphine glucuronides were positively correlated to serum creatinine. Neither pain intensity, evaluated by visual analogue scale (VAS), nor side effects showed any relationship to the CSF M3G concentrations, M3G/M or the M3G/M6G ratios. We conclude that during steady state subcutaneous administration of morphine, there is a large interindividual variation in plasma morphine with poor relationship to the daily administered dose. In CSF this correlation was more evident. Plasma and CSF concentrations of M3G and CSF concentrations of M6G correlated with administered morphine dose. There was an accumulation of both morphine glucuronides in patients with elevated serum creatinine. Measurements of morphine, M3G and M6G in CSF did not show any overt relationship to analgesia or side effects.

Outcomes of epidural morphine treatment in cancer pain: nine years of clinical experience.

The outcome of epidural morphine therapy is described in 146 consecutive cancer patients who were treated by a community hospital-based pain service. The routine procedure used a standard epidural catheter that was tunneled subcutaneously. One hundred and twenty-one patients improved and stayed on lifelong or chronic epidural opioids. Mean treatment time was 92 days (median, 47; range, 2-2040); 49% of the time was spent as outpatients. Twenty-five patients failed to respond to the treatment. The oral daily morphine-equivalent dose prior to inclusion was 164 mg. The mean daily epidural start dose of morphine was 18 mg (range, 6-120), and the mean daily dose at termination was 69 mg (range, 2-540). The dose escalations, described as the ratio of the maximum dose to the minimum maintenance start dose, were moderate, with a mean of 4.1 (median, 2.5), which corresponded to a percent increase of 5.1 (median, 2.7) per patient per day. Lack of effect due to the character of the original symptoms or progression of pain was the main reason for withdrawal from epidural opioid therapy (N = 27), followed by catheter-related problems (N = 9) and drug-related complications (N = 5). Also due to drug-related complications, epidural morphine therapy was changed to buprenorphine or methadone in 19 patients. Adjuvant systemic opioids were given to ten patients and epidural local anesthetics were administered to 17 of the subjects. Neuropathic pain, certain visceral pain types, incident pain on movement, and pain from cutaneous ulcerations were characteristics of poor responders.(ABSTRACT TRUNCATED AT 250 WORDS)

Endoscopic electrocautery of the upper thoracic sympathetic chain: a safe and simple technique for treatment of sympathetically maintained pain.

Transthoracic endoscopic electrocautery of the upper thoracic ganglia was applied to seven patients with sympathetically maintained pain (SMP) in the upper extremity, diagnosed by local anaesthetic stellate ganglion blocks. The mean (SD) pain intensity of 67 (13) mm as evaluated by means of a visual analogue scale was reduced by 79 (27%) postoperatively and this effect persisted after 3 months. Long term follow up comprises two patients so far (one year and two years, respectively) who have had no recurrence of SMP. No complications occurred. The operation was found to be fast, safe and effective and it highlights the enigmatic role of the sympathetic nervous system in chronic pain.

CSF neuropeptides in cancer pain: effects of spinal opioid therapy.

The cerebrospinal fluid (CSF) levels of the opioid peptides met-enkephalin (ME), beta-endorphin (BE) and dynorphin (DYN) as well as the putative sensory neuropeptides substance P (SP), somatostatin (SOM), calcitonin gene related peptide (CGRP) and vasoactive intestinal polypeptide (VIP) were determined in 10 patients with severe nociceptive pain due to malignancy, before and after initiation of spinal opioid therapy, and in 10 control patients. Pain intensity, evaluated by means of a 100-mm visual analog scale (VAS), was reduced from 39 +/- 9 to 18 +/- 10 for continuous pain and from 70 +/- 10 to 10 +/- 8 for intermittent pain (means +/- s.e.mean). Lumbar CSF immunoreactive ME and DYN concentrations were significantly increased (P = 0.05) and BE and VIP were significantly decreased (P < or = 0.05) in the pain patients. A slight, but non-significant (P = 0.06) decrease in SP-like immunoreactivity was found after initiation of spinal opioid therapy. Visceral pain seemed to be associated with low immunoreactive SP and ME concentrations compared to somatic pain. A highly significant correlation was found between SP and ME (P < 0.001) and to a lesser extent also between other peptides. We conclude that the concentrations of the endogenous opioids were more affected by nociceptive pain states than the non-opioid peptides. The origin of pain may also influence the results. The postulated inhibition of peptide release by spinal opioid application seemed to be present for SP, but could otherwise not be confirmed.

Changes in serum zinc during and after surgical procedures.

Serum zinc was followed in 49 patients during and after minor and major surgery. Serum zinc decreases significantly after major operative trauma such as SPV and cholecystecotomy whereas no change can be seen after minor surgery such as hernia repair. The drop is most pronounced 6 hours after the operation. Serum zinc gradually returns to normal level in 2--3 days. In older patients the decrease is more pronounced but return to normal serum zinc level occurs as quickly as in young patients.

Secondary electron conduction camera tube for space applications.

A camera tube based on the SEC (secondary electron conduction) effect has been developed for space applications. The background to the initiation of this development is briefly mentioned and anticipated applications are reviewed. These comprise the use as a detector in astronomical instruments (cameras and spectrographs), in a star field camera, and in special instruments for earth observation. The tube construction is described where it concerns the modifications made to the original standard tube produced by the firm Heimann GmbH. Finally, a first assessment of the tube performance is summarized as measured in a standard test facility operating in the standard European scan format.

Performance testing of electrostatically focused uv-visible image converters with deflection capability.

Two prototype uv to visible image converter tubes with image deflection capability, produced by the En- glish Electric Valve Company, Ltd., have been tested with respect to performance parameters related to the photometric and imaging properties of the tubes. The two converters were electrostatically focused with a triode structure and were magnetically deflectable. The tests were executed at a facility for abso- lute intensity calibrations in the visible and vacuum uv spectral region available at the Max-Planck-Institut für Extraterrestrische Physik. Test procedures and results are reported.