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AbstractBackgroundLeft atrial (LA) strain, comprising LA reservoir, conduit and contractile function could add mechanistic information of patients after arterial switch operation (ASO) for transposition of the great arteries (TGA). ASO patients might have abnormal ventriculoarterial coupling, which makes them vulnerable to left ventricle (LV) dysfunction and results in reduced exercise capacity. This explorative study aimed to evaluate the relation between LA strain, atrial size, ventricular function, and exercise data obtained by cardiopulmonary exercise testing (CPET).MethodsIn a cohort of 44 patients (71% male, mean age 25 ± 4 years) LA strain was measured using transthoracic speckle-tracking echocardiography. Further assessment involved standard echocardiography, CPET evaluation, and blood sampling. LA strain values were compared to normal values. Correlations were calculated. Regression analysis with all strain variables to the CPET data was performed.ResultsLA reservoir, conduit and contractile strain were normal in 30%, 89% and 50% of the patients, respectively. LA reservoir/contractile straincorrelated to LV ejection fraction (ρ0.310/−0.159, respectively) and LA reservoir/conduit straincorrelated to the LA volume index (ρ0.336/−0.357, respectively). None of the individual LA strain parameterswere associated with the CPET variables. In multivariate regression analysis, LA contractile strainwas significantly associated with the percentage of predicted maximal heart rate (β − 2.555).ConclusionsThese data suggest that in TGA patients after ASO repair LA strain is impaired and correlates with LA size and LV function. However, impaired LA strain wasn’t associated with the standard CPET parameters. As such, clinical significance needs to be further unravelled.

AbstractBackgroundData on the evolution of exercise capacity in adults with repaired coarctation of the aorta (CoA) are scarce. We aimed to investigate the evolution and change of measures of exercise capacity obtained by cardiopulmonary exercise testing (CPET) in adults with repaired CoA.MethodsPatients 16 years of age and older with CoA, who performed at least two maximal CPETs in our institution, were included in the study. The first and last available tests were used for comparative statistical analysis of common exercise variables.ResultsSixty patients (43 men) performed serial maximal CPET. Mean age at first assessment was 30 ± 10 years (range 17–68). Mean time between first and last assessment was 3.5 years (range 1–7). Mean peak VO2was 85.6 ± 20.4% of the predicted value at the initial test, and 87.0 ± 20.5% at the final test (p = 0.294). There were no significant differences in the mean values of oxygen pulse, VO2at anaerobic threshold, systolic and diastolic blood pressures and peak heart rate between the two assessments. There was a slightly higher VE/VCO2slope at the final test (p = 0.047). Higher age and Borg scale were found to be related with a decline in percent-predicted peak VO2from initial to final assessment.ConclusionIn adults with repaired CoA, we found no significant change in peak VO2during a mean follow-up of 3.5 years, yet a small increase in VE/VCO2slope was observed. Higher age was predictive for a decline in percent-predicted peak VO2, starting in the third decade of life.

Balance impairment is a frequent cause of morbidity and mortality in people with Parkinson’s disease (PD). As opposed to the effects of appendicular motor symptoms, the effects of Levodopa on balance impairment in idiopathic PD are less clear. To review the literature on the effects of oral Levodopa on clinical balance test performance, posturography, step initiation, and responses to perturbation in people with idiopathic PD (PwPD). A systematic search of three scientific databases (Pubmed, Embase, and Web of Science) was conducted in accordance with PRISMA guidelines. For the pilot meta-analysis, standardized mean differences with 95% confidence intervals were calculated using an inverse variance random effects model. Data not suitable for implementation in the meta-analysis (missing means or standard deviations, and non-independent outcomes) were analyzed narratively. A total of 2772 unique studies were retrieved, of which 18 met the eligibility criteria and were analyzed, including data of 710 idiopathic PwPD. Levodopa had a significant positive effect on the Berg Balance Scale, the Push and Release test, and jerk and frequency parameters during posturography. In contrast, some significant negative effects on velocity-based sway parameters were found during posturography and step initiation. However, Levodopa had no significant effect on most step initiation- and all perturbation parameters. The effects of Levodopa on balance in PwPD vary depending on the outcome parameters and patient inclusion criteria. A systematic approach with well-defined outcome parameters, and prespecified, sensitive and reliable tests is needed in future studies to unravel the effects of oral Levodopa on balance.

The objective of this study was to assess the associations of birth weight with cardiac structure and function in adults with dextro-transposition of the great arteries (D-TGA) who underwent the arterial switch operation (ASO).

Hippocampal sclerosis (HS) is a common neuropathological finding and has been associated with advanced age, TDP-43 proteinopathy, and cerebrovascular pathology. We analyzed neuropathological data of an autopsy cohort of early-onset frontotemporal dementia patients. The study aimed to determine whether in this cohort HS was related to TDP-43 proteinopathy and whether additional factors could be identified. We examined the relationship between HS, proteinopathies in frontotemporal cortices and hippocampus, Alzheimer disease, cerebrovascular changes, and age. We confirmed a strong association between HS and hippocampal TDP-43, whereas there was a weaker association between HS and frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP). Nearly all of the FTLD-TDP cases had TDP-43 pathology in the hippocampus. HS was present in all FTLD-TDP type D cases, in 50% of the FTLD-TDP A cohort and in 6% of the FTLD-TDP B cohort. Our data also showed a significant association between HS and vascular changes. We reviewed the literature on HS and discuss possible pathophysiological mechanisms between TDP-43 pathology, cerebrovascular disease, and HS. Additionally, we introduced a quantitative neuronal cell count in CA1 to objectify the semiquantitative visual appreciation of HS.

The concept of functional movement disorders has evolved considerably over the past few decades. More specifically, the views on the relation with psychological stressors or personality disorders have substantially changed, emphasizing a shift from the previously dominant dualistic scheme. This evolution is reflected in adaptations to diagnostic criteria and management approaches. Functional movement disorders which arise in a close temporal relationship with a peripheral trauma are specifically challenging with respect to diagnosis and treatment, but similar considerations seem to apply. The relationship of functional disorders with trauma appears to be much closer than is often thought. Clinical and pathophysiological research has identified shared factors underlying functional posttraumatic as well as primary movement disorders. These evolving insights impact on discussions in terms of litigation for compensation after trauma. The literature is reviewed and the consequences for argumentation in litigation are outlined, including ethical and legal considerations. Finally, we formulate a number of recommendations.

Magnesium isotopic analysis of cerebrospinal fluid (CSF) is a potentially interesting approach for studies on neurodegeneration. However, this type of analysis is challenging because of the invasiveness of the sampling and small sample volume. In this work, a novel analytical method was developed for ultrasensitive Mg isotopic analysis of CSF microsamples viamulticollector inductively coupled plasma–mass spectrometry (MC-ICP-MS) using high-gain 1013Ω Faraday cup amplifiers. The intermediate and internal errors on the δ26Mg value were improved up to fourfold using 1013Ω resistors for the monitoring of both the 24Mg and 26Mg isotopes and up to twofold using a 1011Ω resistor for the most abundant 24Mg isotope and a 1013Ω resistor for the 26Mg isotope. Magnesium isotope ratios measured at a concentration level of 7–10 μg L–1were in good agreement with those obtained using the conventional method at a concentration level of 150 μg L–1. The expanded uncertainty for the quality control CSF material obtained at the ultratrace level was ±0.16‰. Ultrasensitive Mg isotopic analysis was carried out for CSF from hydrocephalus patients using only 5 μL of sample. δMg values thus obtained were not significantly different from those obtained using the conventional method using a sample volume of 400 μL instead (p≤ 0.05). The Mg isotopic composition of the CSF from hydrocephalus patients ranged between −0.65 and 0.30‰, with a mean δ26Mg value of −0.14 ± 0.27‰.

Oromandibular dystonia (OMD) is a clinically and etiologically heterogeneous form of focal dystonia with variable social and functional implications. The results of pharmacological treatment and botulinum toxin infiltrations are often unsatisfactory. We performed a systematic review on the effects of oral and dental appliances in patients with OMD. Most of the reports in the literature are single subject descriptions or small case series with a considerable variability in the type of dystonia, the type of evaluated appliances and in the outcome measures. Only one report included a large group of unselected patients that were evaluated with a mixture of outcome measures. Although it appears that a number of OMD patients, especially those who benefit from sensory tricks, may sustain some improvement with the use of oral appliances, no definitive conclusions can be drawn about the type of patients that may benefit, nor about the preferred type or mode of appliance. More research in this field is needed, using standardized approaches and clearly defined outcome measures in larger cohorts of OMD patients that are clinically and diagnostically well characterized.

Recovery of stroke-related aphasia can be affected by language therapy in the early and chronic stage. Objectively monitoring therapy-induced neuroplasticity is possible by several measurement techniques including electro- and magneto-encephalography. The obtained event-related potentials (ERPs) and fields (ERFs) provide insights into the neural basis of intact or deficient language processing with milliseconds precision. In this literature review, we highlight the sensitivity of ERPs and ERFs to logopedic interventions by providing an overview of therapy-induced changes in the amplitude, latency and topography of early and mid-to-late components.

ABSTRACTAs small and stable high-affinity antigen binders, VHHs boast attractive characteristics both for therapeutic use in various disease indications, and as versatile reagents in research and diagnostics. To further increase the versatility of VHHs, we explored the VHH scaffold in a structure-guided approach to select regions where the introduction of an N-glycosylation N-X-T sequon and its associated glycan should not interfere with protein folding or epitope recognition. We expressed variants of such glycoengineered VHHs in the Pichia pastorisGlycoSwitchM5 strain, allowing us to pinpoint preferred sites at which Man5GlcNAc2-glycans can be introduced at high site occupancy without affecting antigen binding. A VHH carrying predominantly a Man5GlcNAc2N-glycan at one of these preferred sites showed highly efficient, glycan-dependent uptake by Mf4/4 macrophages invitroand by alveolar lung macrophages invivo, illustrating one potential application of glyco-engineered VHHs: a glycan-based targeting approach for lung macrophage endolysosomal system delivery. The set of optimal artificial VHH N-glycosylation sites identified in this study can serve as a blueprint for targeted glyco-engineering of other VHHs, enabling site-specific functionalization through the rapidly expanding toolbox of synthetic glycobiology.

AbstractAnti-NMDA receptor encephalitis is an autoimmune disorder confirmed by the presence of antibodies against the NMDA-receptor in serum or CSF. This case report describes a young woman with anti-NMDA receptor encephalitis, who presented with prominent psychiatric symptoms. There was a crucial delay in diagnosis and necessary treatment due to the fact that the clinical presentation was diagnosed and treated as a first psychotic episode. Physicians and especially psychiatrists, should consider the possibility of an autoimmune encephalitis in their differential diagnosis in every new onset psychotic episode with rapid progression, the presence of pathognomonic orofacial dyskinesia, the lack of psychiatric history, and the non-responding to psychopharmacological treatment. Early diagnosis and treatment is essential for recovery and may improve the prognosis.

Morality is a complex and versatile concept that necessitates the integrated activity of multiple interacting networks in the brain. Numerous cortical and subcortical areas, many of which are implicated in either emotional and cognitive control or Theory of Mind, are involved in the processing of moral behaviour. Different methods have been used to investigate various aspects of morality, which has lead to confusing and sometimes opposing results. Emotional, cognitive and personality changes have long been recognized in Parkinson’s disease (PD) patients, suggesting a potential impact on moral aspects of behaviour in daily living situations. Alterations in social cognition have been described in all stages of PD but these are rather directly related to PD pathology and not to dopaminergic or DBS treatment. There are no convincing data supporting the hypothesis that dopaminergic treatment or deep brain stimulation of the STN per se interfere with morality in PD patients, although subgroups of patients may display socially unacceptable behaviour. Research in social cognition in PD patients is a fascinating topic that needs further attention in view of the impact on quality of life for PD patients and their caregivers.

The neurophysiology of gait is complex and involves numerous structures in the central nervous system. Gait disorders occur frequently in Parkinson’s disease (PD), and their management may become cumbersome, especially in the more advanced stages. Neuromodulatory treatments, including deep brain stimulation, cortical stimulation and spinal cord stimulation, are reviewed with respect to their effectiveness to improve gait in PD patients. Although positive effects have been reported for all of these procedures, many issues remain in view of methodological heterogeneity, variability in outcome measures and sample size. Gait in PD remains a difficult issue with a tremendous impact on quality of life, for which future research is badly needed.

Auditory phoneme discrimination (APD) is supported by both auditory and motor regions through a sensorimotor interface embedded in a fronto-temporo-parietal cortical network. However, the specific spatiotemporal organization of this network during APD with respect to different types of phonemic contrasts is still unclear. Here, we use source reconstruction, applied to event-related potentials in a group of 47 participants, to uncover a potential spatiotemporal differentiation in these brain regions during a passive and active APD task with respect to place of articulation (PoA), voicing and manner of articulation (MoA). Results demonstrate that in an early stage (50–110 ms), auditory, motor and sensorimotor regions elicit more activation during the passive and active APD task with MoA and active APD task with voicing compared to PoA. In a later stage (130–175 ms), the same auditory and motor regions elicit more activation during the APD task with PoA compared to MoA and voicing, yet only in the active condition, implying important timing differences. Degree of attention influences a frontal network during the APD task with PoA, whereas auditory regions are more affected during the APD task with MoA and voicing. Based on these findings, it can be carefully suggested that APD is supported by the integration of early activation of auditory-acoustic properties in superior temporal regions, more perpetuated for MoA and voicing, and later auditory-to-motor integration in sensorimotor areas, more perpetuated for PoA.

IMPORTANCE: Patients carrying a C9orf72 repeat expansion leading to frontotemporal dementia and/or amyotrophic lateral sclerosis have highly variable ages at onset of disease, suggesting the presence of modifying factors. OBJECTIVE: To provide clinical-based evidence for disease anticipation in families carrying a C9orf72 repeat expansion by analyzing age at onset, disease duration, and age at death in successive generations. DESIGN, SETTING, AND PARTICIPANTS: This cohort study was performed from June 16, 2000, to June 1, 2016, in 36 extended Belgian families in which a C9orf72 repeat expansion was segregating. The generational effect on age at onset, disease duration, and age at death was estimated using a mixed effects Cox proportional hazards regression model, including random-effects terms for within-family correlation and kinship. Time until disease onset or last examination, time from disease onset until death or last examination, or age at death was collected for for 244 individuals (132 proven or obligate C9orf72 carriers), of whom 147 were clinically affected (89 proven or obligate C9orf72 carriers). MAIN OUTCOMES AND MEASURES: Generational effect on age at onset, disease duration, and age at death. RESULTS: Among the 111 individuals with age at onset available (66 men and 45 women; mean [SD] age, 57.2 [9.1] years), the mean (SD) age at onset per generation (from earliest-born to latest-born generation) was 62.5 (8.3), 57.1 (8.2), 54.6 (10.2), and 49.3 (7.5) years. Censored regression analysis on all affected and unaffected at-risk relatives confirmed a decrease in age at onset in successive generations (P < .001). No generational effect was observed for disease duration or age at death. CONCLUSIONS AND RELEVANCE: The clinical data provide supportive evidence for the occurrence of disease anticipation in families carrying a C9orf72 repeat expansion by means of a decrease in age at onset across successive generations. This finding may help clinicians decide from which age onward it may be relevant to clinically follow presymptomatic individuals who carry a C9orf72 repeat expansion.

While the influence of deep brain stimulation (DBS) of the subthalamic nucleus (STN) on the comprehension of pragmatic language in Parkinson’s disease (PD) has been the focus of studies, its impact on production, however, has yet to be elucidated. (1) Investigating the inf luence of DBS STN on pragmatic language production in spontaneous speech by comparing different stimulation conditions and (2) evaluating the effect of asymmetric dopaminergic denervation. This paper included 18 patients with advanced idiopathic PD with STN DBS. [Ten PD patients with predominantly left hemispheric dopamine denervation (PD-left) and eight PD patients with predominantly right-hemispheric dopamine denervation (PD-right).] The pragmatic components ‘communicative functions’ and ‘conversational skills’ were evaluated by analysing the spontaneous language production in four stimulation conditions. STN stimulation did not appear to influence the pragmatic production skills. Only when asymmetric dopamine depletion was taken into account the parameter ‘giving an explanation’ interaction was detectable. STN DBS appears to have some influence on the production of pragmatic language depending on asymmetric dopaminergic denervation. Suggestions are made for further research of pragmatic production in Parkinson’s disease.

To identify the genetic cause in 2 Belgian families with autosomal recessive Huntington-like disorder (HDL).

Patients with a systemic right ventricle (sRV) have a high risk of developing heart failure (HF), with heart transplantation as the only long-term treatment option. Unfortunately, more than half of sRV patients have pulmonary hypertension (PH) which may impact the decision to opt for heart-only transplantation. Moreover, an increased scarcity of donor hearts prolongs time to transplantation, increasing the probability of dying on the waiting list. Hence, for selected sRV patients, a ventricular assist device (VAD) could provide a solution to bridge the time to transplantation. This case series aimed at evaluating all patients with a sRV who received a VAD at our institution, with a focus on technical aspects of VAD implantation and invasive hemodynamics prior to VAD implantation and after heart transplantation.

OBJECTIVE To characterize patients with frontotemporal lobar degeneration (FTLD) with a repeat expansion mutation in the gene C9orf72, and to determine whether there are differences in the clinical presentation compared with FTLD carriers of a mutation in GRN or MAPT or with patients with FTLD without mutation. DESIGN Patient series. SETTING Dementia clinics in Flanders, Belgium. PATIENTS Two hundred seventy-five genetically and phenotypically thoroughly characterized patients with FTLD. MAIN OUTCOME MEASURES Clinical and demographic characteristics of 26 C9orf72 expansion carriers compared with patients with a GRN or MAPT mutation, as well as patients with familial and sporadic FTLD without mutation. RESULTS C9orf72 expansion carriers developed FTLD at an early age (average, 55.3 years; range, 42-69 years), significantly earlier than in GRN mutation carriers or patients with FTLD without mutation. Mean survival (6.2 years; range, 1.5-17.0 years) was similar to other patient groups. Most developed behavioral variant frontotemporal dementia (85%), with disinhibited behavior as the prominent feature. Concomitant amyotrophic lateral sclerosis is a strong distinguishing feature for C9orf72 -associated FTLD. However, in most patients (73%), amyotrophic lateral sclerosis symptoms were absent. Compared with C9orf72 expansion carriers, nonfluent aphasia and limb apraxia were significantly more common in GRN mutation carriers. CONCLUSIONS C9orf72 -associated FTLD most often presents with early-onset behavioral variant frontotemporal dementia with disinhibition as the prominent feature, with or without amyotrophic lateral sclerosis. Based on the observed genotype-phenotype correlations between the different FTLD syndromes and different genetic causes, we propose a decision tree to guide clinical genetic testing in patients clinically diagnosed as having FTLD.

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a complex neurodegenerative disorder caused by mutations in SACS. The phenotype consists of a childhood-onset triad of cerebellar ataxia, peripheral neuropathy, and pyramidal tract signs.

To verify the applicability of a recently described resolution-independent method for the semi-quantification of 123I-FP-CIT scans.

BACKGROUND Progranulin gene (PGRN) haploinsufficiency was recently associated with ubiquitin-positive frontotemporal lobar degeneration linked to chromosome 17q21 (FTLDU-17). OBJECTIVE To assess whether PGRN genetic variability contributed to other common neurodegenerative brain diseases, such as Alzheimer disease (AD) or Parkinson disease (PD). DESIGN Mutation analysis of PGRN SETTING Memory Clinic of the Middelheim General Hospital. PATIENTS We analyzed 666 Belgian patients with AD and 255 with PD. MAIN OUTCOME MEASURES Results of PGRN sequencing, PGRN transcript analysis, short tandem repeat genotyping, and neuropathologic analysis. RESULTS We identified 2 patients with AD and 1 patient with PD who carried the null mutation IVS0 + 5G>C, which we reported earlier in an extensively characterized Belgian founder family, DR8, segregating FTLDU. Postmortem pathologic diagnosis of the patient with PD revealed both FTLDU and Lewy body pathologic features. In addition, we identified in PGRN only 1 other null mutation, the nonsense mutation p.Arg535X, in 1 patient with probable AD. However, in vitro analysis predicted a PGRN C-truncated protein, although it remains to be elucidated if this shortened transcript leads to haploinsufficiency. CONCLUSIONS Our mutation data indicated that null mutations are rare in patients with AD (3/666 = 0.45%) and PD (1/255 = 0.39%). Also, AD and PD clinical diagnoses in patients who carry PGRN null mutations likely result from etiologic heterogeneity rather than PGRN haploinsufficiency.Arch Neurol. 2007;64:(10)938-944--

Abstract: Het kader waarbinnen wij werken is cognitief gedragstherapeutisch: wij zijn ervan overtuigd dat een persoon met een afhankelijkheidsprobleem kan leren anders te denken en dingen anders aan te pakken dan voorheen en hierdoor meer vat kan krijgen op problematisch middelengebruik of verslaving. Ondanks motivatie en inzet, zowel van het team als van de cliënten, worden we herhaaldelijk geconfronteerd met terugval of oncontroleerbare craving (drang naar gebruik). De cognitief gedragstherapeutische werkwijze heeft haar beperkingen. We bespreken kort enkele verklaringen hiervoor en de therapeutische implicaties ervan.

Among patients with frontotemporal lobar degeneration (FTLD), the respective frequencies of dominant 17q21-linked tau-negative FTLD (with unidentified molecular defect) and 17q21-linked tau-positive FTLD (due to MAPT mutations) remain unknown. Here, in a series of 98 genealogically unrelated Belgian FTLD patients, we identified an ancestral 8 cM MAPT containing haplotype in two patients belonging to multiplex families DR2 and DR8, without demonstrable MAPT mutations, in which FTLD was conclusively linked to 17q21 [maximum summed log of the odds (LOD) score of 5.28 at D17S931]. Interestingly, the same DR2–DR8 ancestral haplotype was observed in five additional familial FTLD patients, indicative of a founder effect. In the FTLD series, the DR2–DR8 ancestral haplotype explained 7% (7 out of 98) of FTLD and 17% (7 out of 42) of familial FTLD and was seven times more frequent than MAPT mutations (1 out of 98 or 1%). Clinically, DR2–DR8 haplotype carriers presented with FTLD often characterized by language impairment, and in one carrier the neuropathological diagnosis was FTLD with rare tau-negative ubiquitin-positive inclusions. Together, these results strongly suggest that the DR2–DR8 founder haplotype at 17q21 harbours a tau-negative FTLD causing mutation that is a much more frequent cause of FTLD in Belgium than MAPT mutations.

We have systematically studied the subjective postural vertical (SPV) and the location of the centre of gravity (COG) in right brain damaged patients, classified according to the severity of their hemispatial neglect. The results indicate that the patients lean towards the side of space where they feel aligned with their ipsilesionally displaced SPV, resulting in a ipsilesional deviation of the COG. This displacement can be reduced by the effect of contralesionally applied transcutaneous electrical nerve stimulation (TENS). However, in the severe neglect patients, an increasing mismatch arised between the perceived body orientation and the direction of the gravitational force. The results indicate that this conflict is compensated by a contraversive shift of the COG towards the contraversive side in order to re-align the SPV with the gravitational vertical.

The aetiology of Parkinson's disease (PD) is unknown and said to be multifactorial. We report on a retrospective epidemiological case control study, performed in Flanders during a 3-year period, investigating known and potential environmental risk factors for PD by means of questionnaires. We investigated 423 prevalent patients and 205 spouse-controls. We found familial occurrence in 15% of the patients, a mean age of onset of 58 years, and a clear male preponderance (male/female ratio 1.53). Our results suggest more nulliparity among female PD patients (95% CI: 1.08–5.76). We found a discrete clustering of patients in areas with intensive metallurgic activity. Patients were more frequently employed in metallurgy than controls (95% CI: 1.04–9.20). Furthermore, patients were clearly more exposed to zinc (95% CI: 1.51–90.90) and toluene (95% CI: 1.03–58.82). Male patients report more prostatectomy-surgery (95% CI: 1.54–17.24).

Positron emission tomography (PET) was used to observe changes in regional cerebral blood flow (rCBF) in 10 right-handed healthy volunteers performing two paradigms of mental rotation. In one paradigm, subjects mentally rotated a single alphanumeric stimulus to determine whether it was shown in a normal or mirror-image position. In a second paradigm, subjects mentally rotated and compared pairs of figurative stimuli to determine whether the stimuli were identical or mirror-images. In both paradigms, rCBF was compared with a control task that used identical stimuli, but required no mental rotation. Mental rotation of single alphanumeric stimuli engendered activation in the primary somatomotor area in the left precentral gyrus. Mental rotation of paired figures engendered activation in the left superior parietal lobule and the right frontal medial gyrus. A deactivated area was located in the medial part of the left superior frontal gyrus. Comparison of both paradigms revealed that the left gyrus precentralis was activated significantly during the alphanumeric condition and that the left gyrus lingualis was significantly activated during the paired figures condition. Motor processes may be an inherent part of every mental rotation but the type of motor involvement appears strongly dependent on the specific task or the specific stimuli. Similar paradigms, designed to isolate the same cognitive function, in the same subjects, using the same imaging technology and methodology, but differing only in stimulus material, lead to different areas of neural activation. Task specificity determines the most significant changes in cerebral blood flow in different mental rotation paradigms.

Purpose:The present study investigates the vascular nature of parkinsonian features in patients with ‘probable’ vascular dementia. Patients and Methods:Forty patients with vascular dementia were studied with positron emission tomography (PET) using the steady state technique with 15O in order to assess regional cerebral blood flow (rCBF), regional oxygen extraction rate (rOER) and regional metabolic rate for oxygen (rCMRO2) in different brain regions. The findings in 10 patients with (VaDP) were compared to 30 without parkinsonism (VaD). Results:The clinical and computed tomographic findings in the parkinsonian patients were similar to those described in the literature as probable vascular parkinsonism. The PET results showed decreased rCBF and rCMRO2 in the frontal and parietal cortices and in the striatum of the VaDP compared to the VaD group. The decrease of rCBF and rCMRO2 in frontal and parietal cortices is due to the more severe mental changes in the VaDP group. In the VaDP patients rCBF and rCMRO2 were more decreased and rOER increased in the striatum contralateral to the most affected parkinsonian side. Conclusion:Our PET findings show that local ischemic changes in the striatum contribute to parkinsonism in vascular dementia patients.

High-frequency stimulation of the internal pallidum is an effective surgical approach for patients with advanced Parkinson's disease suffering from motor fluctuations and L-dopa induced dyskinesia. To study the acute effects of internal pallidum stimulation, changes in cerebral blood flow were measured by means of a single-day split-dose protocol using 99Tcm-ECD SPET. Nine patients with advanced Parkinson's disease and with a clinical picture predominated by tremor and drug-induced dyskinesia, were imaged before and immediately after electrostimulation. Brain perfusion data were mirrored to the same electrode side (five left and four right implants), co-registered and analysed statistically on a voxel-by-voxel basis (Statistical Parametric Mapping) and by an automated volume-of-interest approach. Acute stimulation of the internal pallidum induced a significantly decreased perfusion in the ipsilateral thalamus and striatum, as well as in the right parietal cortex. For the subgroup of seven patients with effective motor score improvements, a significant correlation between thalamic and striatal perfusion changes and UPDRS III motor score was present (P0.04). These results suggest that effective stimulation of the internal globus pallidus may produce symptom relief through decreased activity in pallido-thalamo-cortical circuits.

The highest concentrations of the peripheral benzodiazepine receptor (PBR) are found in the kidneys and heart. In addition, the PBR has been reported to reflect neuro-inflammatory damage by co-localisation with activated microglia. PK 11195 is a high-affinity ligand for the PBR. The aim of this study was to investigate in humans the biodistribution and dosimetry of [123I]iodo-PK 11195, a potential single-photon emission tomography tracer for the PBR. Five healthy volunteers were injected with 112 MBq of [123I]iodo-PK 11195. Sequential whole-body scans were performed up to 72 h post injection. Multiple blood samples were taken, and urine was collected to measure the fraction voided by the renal system. Decay-corrected regions of interest of the whole-body images were analysed, and geometric mean count rates were used to determine organ activity. Organ absorbed doses and effective dose were calculated using the MIRD method. [123I]iodo-PK 11195 was rapidly cleared from the blood, mainly by the hepatobiliary system. Approximately 22% was voided in urine after 48 h. Average organ residence times were 0.74, 0.44 and 0.29 h for the liver, upper large intestine and lower large intestine, respectively. The testes received the highest dose, 109.4 µGy/MBq. All other organs investigated received doses of less than 50 µGy/MBq. The effective dose was 40.3 µSv/MBq. In conclusion, [123I]iodo-PK 11195 is a suitable agent for the visualisation of the PBR and indirectly for the imaging of neuro-inflammatory lesions. Taking into account the radiation burden of 7.46 mSv following an administration of 185 MBq, a [123I]iodo-PK 11195 investigation has to be considered an ICRP risk category IIb investigation.

The synthesis of two ¹¹C labelled chromeno[3,4-c]pyridin-5-ones for the visualisation of the dopamine D4 receptor subtype has been developed. The production entailed an O-methylation of the O-desmethyl precursor with [¹¹C]iodomethane in the presence of tetrabutylammonium hydroxide. Subsequent purification by RP-HPLC and formulation by tracer enrichment on a C18 Sep Pak provided a solution which was suitable for human iv injection. Specific activity of the tracer averaged 37 GBq/μmol at EOS and the radiochemical yields were 65% (decay-corrected, based on [¹¹C]CH3I). Total activity obtained was 5·6–7·4 GBq. The preparations have been demonstrated to be chemically and radiochemically pure by HPLC. Copyright © 2000 John Wiley & Sons, Ltd.

We investigated the lipoprotein distribution and composition in cerebrospinal fluid (CSF) in a group of patients with Alzheimer's disease (AD) or affected by other types of dementia in comparison to non-demented controls. We found slightly decreased apolipoprotein (apo)E and cholesterol concentrations in CSF of AD patients and moderately increased apoA-I concentrations, while in patients suffering from other types of dementia the apoA-I CSF concentration was increased. ApoA-IV concentrations varied widely in human CSF, but were not associated with any clinical condition. HDL(2)-like apoE-containing lipoproteins represent the major lipoprotein fraction. In CSF of normal controls, only a minor HDL(3)-like apoA-I-containing lipoprotein fraction was observed; this fraction was more prevalent in AD patients. ApoA-II was recovered mostly in the HDL(3) density range, while apoA-IV was not associated with lipoproteins but appeared in a lipid-free form, co-localizing with LCAT immunoreactivity. Bi-dimensional analysis demonstrated pre-beta and alpha apoA-I-containing particles; apoE and apoA-II were detected only in alpha-migrating particles. ApoA-IV distributed both to pre-beta and gamma-migrating particles; the LCAT signal was co-localized in this gamma-migrating fraction. Enzymatically active LCAT was present in human CSF as well as PLTP activity and mass; no CETP mass was detected. In CSF from AD patients, LCAT activity was 50% lower than in CSF from normal controls. CSF lipoproteins induced a significant cholesterol efflux from cultured rat astrocytes, suggesting that they play an active role in maintaining the cholesterol homeostasis in brain cells.

Donepezil (1-benzyl-4-[(5,6-dimethoxy-1-oxoindan-2-yl)methyl-]piperidine), a potent acetylcholine esterase inhibitor, was labelled with [¹¹C]iodomethane by O-methylation of the O-6'-desmethyl precursor. Synthesis, purification and formulation were performed in approximately 30 min with an average specific activity of 39.5 GBq/μmol at EOS. The total activity available for applications was 7.5–11.1 GBq. Copyright © 2000 John Wiley & Sons, Ltd.

Permanent turbulent air flow at low Mach number does not disturb the longitudinal gradient of mean pressure associated with acoustic streaming, while the profile of mean axial velocities of the air flow is not appreciably modified when it is subjected to the wave generating the acoustic streaming. This is highlighted by the present experiments and discussed in the theoretical framework initially proposed by Rayleigh, then generalized by Nyborg and Westervelt. The result is, on the one hand, the possibility of predicting simply the Reynolds stress exerted on a permanent turbulent air flow subjected to a wave generating acoustic streaming, and on the other hand, the very likely absence of any influence of permanent turbulent air flow on acoustic streaming.

Cobalt-55 (^5^5Co) has been shown to be an interesting positron emission tomography (PET) tracer that may reflect calcium (Ca) influx in damaged cerebral tissue. Because Ca load is important in the ischemic cascade, the exact meaning of ^5^5Co PET in stroke patients has to be shown. The present study compares the degree of ^5^5Co uptake to regional cerebral blood flow (rCBF) and regional cerebral metabolic rate for oxygen (rCMRO"2) values in brains of patients with ischemic stroke. Eighteen patients with an ischemic event in the middle cerebral artery territory were examined with PET using, in the same session, ^5^5Co and the ^1^5O steady state technique. The ^5^5Co ratio was assessed in ischemic and infarcted regions and compared with the corresponding rCBF and rCMRO"2 values. The average ^5^5Co ratio is inversely correlated to the rCBF and rCMRO"2 values. Also ^5^5Co accumulation tends to increase during the weeks after the onset of stroke and decreases down to normal levels after 6 months. The degree of ^5^5Co uptake corresponds to the severity of the ischemic damage within the first month after stroke. As it increases with time, it probably reflects the Ca accumulation caused by the progression of the inflammatory response within and around the infarct core

Cobalt-55 (55Co) is a positron emission tomography (PET) tracer used to demonstrate brain damage, possibly associated to calcium-mediated processes. The degree of 55Co accumulation correlates with the severity of ischaemia in stroke patients. It is still a matter of debate whether ipsilateral thalamic hypometabolism (ITH) and crossed cerebellar hypometabolism (CCH), occurring after middle cerebral artery (MCA) infarcts, represent only a metabolic depression of these remote regions or can lead to structural damage. The present study investigates whether an increased 55Co influx can be demonstrated with PET in ITH and CCH after MCA infarcts. About half of the patients with ITH and CCH had a significant degree of 55Co uptake in, respectively, the ipsilateral thalamus and the contralateral cerebellar hemisphere. It was observed in patients with severe signs of stroke on admission and poor clinical outcome, and correlated well with the degree of 55Co influx within the supratentorial infarct. The present study demonstrates that ITH and CCH after MCA infarction can represent structural damage in these remote areas that occurs during the second week after stroke onset.

Two patients presenting with progressive dysarthria as the single initial manifestation of a neurodegenerative condition are described. The nature of the dysarthria as well as the additional symptoms that developed in the course of the disorder are very different in these two cases. Nevertheless, neuroimaging findings are strikingly similar and suggest bilateral involvement of posterior inferior frontal lobe structures, mainly in the dominant cerebral hemisphere. The clinical syndrome of these patients can therefore be considered an example of frontotemporal degeneration presenting without dementia or comportmental alteration, at least in the early stages. This broadens the clinical spectrum of frontotemporal degeneration and demonstrates the need for a syndromal subclassification of this nosological entity.

The purpose of this study was to determine the effect of different durations of static stretching exercises on coxo-femoral (hip) flexibility. The experimental group, consisting of 20 sedentary women (20-30 years of age), participated in an exercise programme of static stretching exercises with emphasis on the hamstring muscles. The programme lasted for 10 weeks and consisted of two 50-min sessions per week. A control group of 15 sedentary women did not participate in the programme. Hip flexibility was determined before, during and at the end of the programme by means of a goniometric measuring technique developed by us and described elsewhere. Three sub-groups were formed, each following the same programme except that the duration of the static stretch differed (group 1,10 s; group 2, 20 s; group 3, 30 s). The ANOVA tests showed that for all groups - the control group excepted - the hip flexibility had improved significantly after 10 weeks (P <0.05). No significant differences in hip flexibility were noted between the three subgroups at the end of the programme. This finding suggests that a duration of 10 s static stretching is sufficient for improving coxo-femoral flexibility.