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Patrick Santens

Publications and source records attributed to Patrick Santens.

At least 19 recordsLinked to original sources
PubMed2006

Quantification of Parkinson's disease-related network expression with ECD SPECT.

PURPOSE: Spatial covariance analysis has been used with FDG PET to identify a specific metabolic network associated with Parkinson's disease (PD). In the current study, we utilized a new, fully automated voxel-based method to quantify network expression in ECD SPECT images from patients with classical PD, patients with multiple system atrophy (MSA), and healthy control subjects. METHODS: We applied a previously validated voxel-based PD-related covariance pattern (PDRP) to quantify network expression in the ECD SPECT scans of 35 PD patients, 15 age- and disease severity-matched MSA patients, and 35 age-matched healthy control subjects. PDRP scores were compared across groups using analysis of variance. The sensitivity and specificity of the prospectively computed PDRP scores in the differential diagnosis of individual subjects were assessed by receiver operating characteristic (ROC) analysis. RESULTS: PDRP scores were significantly increased (p < 0.001) in the PD group relative to the MSA and control groups. ROC analysis indicated that the overall diagnostic accuracy of the PDRP measures was 0.91 (AUC). The optimal cutoff value was consistent with a sensitivity of 0.97 and a specificity of 0.80 and 0.71 for discriminating PD patients from MSA and normal controls, respectively. CONCLUSION: Our findings suggest that fully automated voxel-based network assessment techniques can be used to quantify network expression in the ECD SPECT scans of parkinsonian patients.

Algorithms↗
PubMed2006

Null mutations in progranulin cause ubiquitin-positive frontotemporal dementia linked to chromosome 17q21.

Frontotemporal dementia (FTD) with ubiquitin-immunoreactive neuronal inclusions (both cytoplasmic and nuclear) of unknown nature has been linked to a chromosome 17q21 region (FTDU-17) containing MAPT (microtubule-associated protein tau). FTDU-17 patients have consistently been shown to lack a tau-immunoreactive pathology, a feature characteristic of FTD with parkinsonism linked to mutations in MAPT (FTDP-17). Furthermore, in FTDU-17 patients, mutations in MAPT and genomic rearrangements in the MAPT region have been excluded by both genomic sequencing and fluorescence in situ hybridization on mechanically stretched chromosomes. Here we demonstrate that FTDU-17 is caused by mutations in the gene coding for progranulin (PGRN), a growth factor involved in multiple physiological and pathological processes including tumorigenesis. Besides the production of truncated PGRN proteins due to premature stop codons, we identified a mutation within the splice donor site of intron 0 (IVS0 + 5G > C), indicating loss of the mutant transcript by nuclear degradation. The finding was made within an extensively documented Belgian FTDU-17 founder family. Transcript and protein analyses confirmed the absence of the mutant allele and a reduction in the expression of PGRN. We also identified a mutation (c.3G > A) in the Met1 translation initiation codon, indicating loss of PGRN due to lack of translation of the mutant allele. Our data provide evidence that PGRN haploinsufficiency leads to neurodegeneration because of reduced PGRN-mediated neuronal survival. Furthermore, in a Belgian series of familial FTD patients, PGRN mutations were 3.5 times more frequent than mutations in MAPT, underscoring a principal involvement of PGRN in FTD pathogenesis.

Belgium↗
PubMed2006

A Belgian ancestral haplotype harbours a highly prevalent mutation for 17q21-linked tau-negative FTLD.

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.

Adolescent↗
PubMed2006

Levodopa-induced alterations in speech rate in advanced Parkinson's disease.

The effect of speech rate on overall intelligibility in Parkinson's Disease (PD) is still a matter of debate. A comparison of the results of previous studies on speech rate in PD is hampered by methodological differences. In this study, we evaluated the effects of levodopa on speech rate and on its variability in a standardized reading task. Twenty-five patients were studied before and after levodopa administration while reading a standardized text. In accordance with previous studies, no significant improvement of speech rate was found. Rather an increased variability of speech rate in the on-medication state could be demonstrated. It is possible that this increased variability may be the consequence of respiratory deficits due to levodopa-induced dyskinesia or an increase of dysfluencies. However, the effects of defective auditory feedback and disturbed executive function cannot be ruled out.

Antiparkinson Agents↗
PubMed2006

Detection of motor and non-motor symptoms of end-of dose wearing-off in Parkinson's disease using a dedicated questionnaire: a Belgian multicenter survey.

In this report the usefulness of a dedicated questionnaire to detect end-of-dose wearing-off (EODWO) fluctuations in PD was studied. One hundred and sixty patients were administered an 18-item questionnaire encompassing both motor and non-motor phenomena. One hundred and eight (86%) reported EODWO, defined as the occurrence of at least one symptom improving by drug intake. Motor phenomena were significantly more frequent and non-motor phenomena never occurred in isolation. This questionnaire was deemed useful by most participants.

Aged↗
PubMed2005

Deep brain stimulation of the internal pallidum in multiple system atrophy.

We describe the outcome of deep brain stimulation of the internal pallidum in a 57-year old patient with multiple system atrophy. Although the prominent dystonic features of this patient were markedly attenuated post-operatively, the outcome was to be considered unfavourable. There was a severe increase in akinesia resulting in overall decrease of mobility in limbs as well as in the face. As a result, the patient was anarthric and displayed dysphagia. A laterality effect of stimulation on oro-facial movements was demonstrated. The patient died 7 months post-operatively. This report adds to the growing consensus that multiple system atrophy patients are unsuitable candidates for deep brain stimulation.

Deep Brain Stimulation↗
PubMed2005

Impaired intentional content learning but spared incidental retention of contextual information in non-demented patients with Parkinson's disease.

We investigated the incidental and intentional learning performance of 29 patients with idiopathic Parkinson's disease (PD) and 20 healthy volunteers. Measures of incidental and intentional memory were assessed with a spoken verbal recall task followed by a temporal word order task, a picture recall task followed by a spatial picture location task, and a written word recall task followed by a judgement of word frequency task. A multivariate analysis of variance and appropriate post hoc tests revealed significant differences for all intentional learning variables. In all cases, PD patients performed worse than normal controls. No group differences were found for the incidental retention of contextual information. The results indicate that PD patients have a selective problem of intentional learning, whereas incidental learning of contextual information remains intact. Elaborate processing, attentional and organizing strategies in the systematic encoding, and recollection of information have been attributed to dorsolateral prefrontal activation. Preferential dysfunction of dorsolateral prefrontal cortex-associated memory processes is consistent with the previously reported uneven patterns of dopamine loss in the striatum of patients with idiopathic PD showing most severe dopamine depletion in the portion of the caudate nucleus that is anatomically connected to the dorsolateral frontal cortex.

Aged↗
PubMed2005

Three cases of substitution errors leading to hyoscine hydrobromide overdose.

We report three patients with anticholinergic poisoning caused by the substitution of hyoscine hydrobromide for hyoscine butylbromide in preparations compounded by two different pharmacists. The patients took the preparations for gastrointes tinal discomfort and presented with altered mental status tachycardia, facial flushing, dilated pupils, and dry skin shortly after the ingestion. In one patient the intoxication was initially not recognized and he was treated as suffering from an acute cerebrovascular accident. Two patients experienced long-lasting effects such as decreased ability to concentrate, memory dis turbances, tremor, and photo- and phonophobia. It was obviously impossible to elucidate the exact nature of the relationship between the intoxication and these long-lasting complaints. Information from the Belgian poison control center revealed that cases of substitution error with hyoscine hydrobromide are not unique The Belgian authorities issued a warning to all pharmacists.

Adult↗
PubMed2004

The effects of levodopa on word intelligibility in Parkinson's disease.

Dysarthria is a common manifestation in patients with idiopathic Parkinson's disease. This study investigated the effects of levodopa on intelligibility in patients with Parkinson's disease. Ten participants were tested during on- and off-states using the Yorkston and Beukelman intelligibility test (1980). Intelligibility as scored by a panel of speech therapists was significantly improved in the on-condition. No correlation was found, however, between intelligibility and overall severity of the disease or severity of the motor problems. EDUCATIONAL OUTCOMES: As a result of this activity the participant will be able to discuss the effects of levodopa on intelligibility in patients with Parkinson's disease.

Aged↗
PubMed2004

Treatment of Parkinson's disease with pergolide and relation to restrictive valvular heart disease.

BACKGROUND: Restrictive valvular heart disease has been reported in patients with Parkinson's disease treated with pergolide. However, few data are available on frequency, severity, dose dependency, and reversibility of pergolide-induced disease, nor on the pulmonary pressures of these patients. We aimed to clarify these characteristics in a large group of patients. METHODS: 78 patients with Parkinson's disease treated with pergolide and 18 never treated with an ergot-derived dopamine agonist (controls) were evaluated by echocardiography. A valvular scoring system was used, ranging from 1 (proven ergot-like restrictive valvular heart disease) to 4 (no disease). For the mitral valve, tenting areas and tenting distances were measured. Systolic pulmonary artery pressures were derived from the tricuspid regurgitant jet. FINDINGS: Restrictive valvular heart disease of any type was present in 26 (33%) patients in the pergolide group and none in controls (p=0.0025). Important disease (score 1 or 2) was present in 15 (19%) patients in the pergolide group and none in controls (p=0.066). Mean tenting distances and tenting areas of the mitral valve were 1.08 cm (range 0.55-2.66) and 2.39 cm2 (0.88-4.59) in the restrictive mitral valve group versus 0.63 cm (0.22-1.20) and 1.39 cm2 (0.39-3.23) in the non-restrictive group (p=0.003 and p<0.0001, respectively). Significant correlation was noted between cumulative doses of pergolide and tenting areas of the mitral valves (r=0.412, p=0.017). Mean systolic pulmonary artery pressures were 39.3 mm Hg (range 25-71) in the high-dose group versus 38.5 mm Hg (20-65) in the low-dose group (p=0.76) and 31 mm Hg (25-40) in controls (p=0.02 vs all patients given pergolide). In six patients, pergolide treatment was stopped because of restrictive valvular heart disease, in two of whom regression of disease was shown. INTERPRETATION: Restrictive valvular heart disease is not a rare finding in patients treated with pergolide. Clinicians should consider changing to a non-ergot drug if this disease is diagnosed.

Aged↗
PubMed2004

Graviceptive misperception of the postural vertical after right hemisphere damage.

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 arose 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.

Adult↗
PubMed2004

Cobalt-55 positron emission tomography in symptomatic atherosclerotic carotid artery disease: borderzone versus territorial infarcts.

BACKGROUND: Borderzone as well as territorial infarcts can occur in severe atherosclerotic carotid artery disease. It remains controversial whether the borderzone distribution of infarcts is due to hypoperfusion or due to artery-to-artery embolism. PURPOSE: The present study investigates whether cobalt-55 (55Co) positron emission tomography (PET) shows a different pattern of ischaemia according to the topography of the infarct in severe atherosclerotic carotid artery disease. PATIENTS AND METHODS: Five patients with a cortical borderzone and seven with a territorial infarct, due to symptomatic carotid artery disease, were investigated with 55Co PET 3-6 months after stroke. Average 55Co counts in the infarct area, the adjacent cortical zone, the deep white matter and, contralateral cerebral cortex and white matter, were compared to the values in the cerebellum used as reference. RESULTS: No differences in 55Co ratio were observed in the different regions of interest (ROIs) between patients with cortical borderzone and those with territorial infarcts. The 55Co uptake was similar or lower than the reference value for all ROIs in all individual patients. CONCLUSION: In patients with borderzone as well as with territorial infarcts no evidence was found for subclinical ischaemic injury in or around the infarcts. These data do support the conclusion that cortical borderzone infarcts may not be due to ongoing chronic haemodynamic impairment, but by no means is this conclusive evidence.

Adult↗
PubMed2004

Statistical parametric mapping of (99m)Tc-ECD SPECT in idiopathic Parkinson's disease and multiple system atrophy with predominant parkinsonian features: correlation with clinical parameters.

UNLABELLED: Statistical parametric mapping was performed to investigate differences in regional cerebral blood flow (rCBF) between patients with idiopathic Parkinson's disease (IPD), patients with multiple system atrophy (MSA), and healthy volunteers. In addition, a voxel-based covariance analysis was performed with disease-specific parameters and clinical patient data such as disease duration, medication, and clinical subscores. METHODS: For this purpose, (99m)Tc-ethylcysteine dimer (ECD) SPECT was performed on 81 IPD patients (50 men, 31 women; age, 62.6 +/- 10.2 y), 15 MSA patients (9 men, 6 women; age, 61.5 +/- 9.2 y), and 44 age- and sex-matched healthy volunteers (27 men, 17 women; age, 59.2 +/- 11.9 y). RESULTS: Significant hypoperfusion was observed in IPD compared with healthy subjects in a symmetric subcortical-cortical network including the basal ganglia, thalami, prefrontal and lateral frontal cortex, and parietooccipital cortex (voxel P value P(height) < 0.001, corrected for multiple comparisons). For MSA, only symmetric hypoperfusion was seen in the putamen and thalamus with respect to healthy subjects and to IPD (P(height) < 0.01, corrected). Prolonged disease duration or higher Hoehn and Yahr stage results in hypoperfusion of the posterior associative cortex. There is a negative correlation between perfusion of the caudate heads and limbic system and the standardized dosage of dopamine agonists in the patients with PD, whereas for MSA a bilateral decrease in putamen activity was noted (P(height) < 0.001, uncorrected). Cognitive performance was positively correlated with limbic perfusion and inversely correlated with posterior associative cortical areas, but not with prefrontal regions. CONCLUSION: Voxel-based analysis of (99m)Tc-ECD perfusion SPECT shows detailed differences between IPD and MSA, which may be of use in the differentiation of both disease entities, and is able to elucidate cerebral perfusion correlates of disease severity, dopamine agonist medication, and cognitive performance.

Algorithms↗
PubMed2003

fMRI of developmental stuttering: a pilot study.

The purpose of this investigation was to explore the feasibility of fMRI in the study of developmental stuttering. Speech contrasts (loud versus silent reading) and language contrasts (reading of semantically meaningful text versus nonsense words) of six developmental stutterers and six nonstutterers were compared using a commercial 1 Tesla MR-Scanner (Siemens Expert). Results indicate that mapping cortical function in persons who stutter is indeed feasible, even with a 1TMR-system. Compared to normals the stutterers seemed to employ different and particularly less differentiated auditory and motor feedback strategies in speech. They apparently rely on auditory processing and on cerebellar contribution as much during silent reading as during reading aloud. Moreover, they showed a greater involvement of the right hemisphere in language processing, activating not only the typical language areas on the left but also and with equal magnitude the right side homologues of these areas. In spite of the promising results, at present several practical problems such as possible movement artifacts and possible masking through scanner noise still hamper a more straightforward use of fMRI in the study of developmental stuttering.

Adult↗
PubMed2003

Thalamic stuttering: a distinct clinical entity?

A 38-year-old right-handed male with no history of speech or language problems presented with neurogenic stuttering following an ischaemic lesion of the left thalamus. He stuttered severely in propositional speech (conversation, monologue, confrontation naming, and word retrieval) but only slightly in non-propositional speech (automatic speech, sound, word and sentence repetition, and reading aloud). It is suggested that thalamic stuttering may constitute a distinct clinical entity.

Brain↗
PubMed2003

Lateralized effects of subthalamic nucleus stimulation on different aspects of speech in Parkinson's disease.

In this report, we have analyzed the effects of left and right STN stimulation separately on different aspects of speech. Significant differences were found between left and right stimulation. It appears that selective left-sided stimulation has a profoundly negative effect on prosody, articulation and hence intelligibility. Right-sided stimulation does not display this side-effect. There is no significant difference in speech characteristics between bilateral stimulation on and off. We suggest that a balanced tuning of bilateral basal ganglia networks is necessary for speech, and that the left circuit is probably dominant.

Adult↗
PubMed2003

Case-control study of environmental risk factors for Parkinson's disease in Belgium.

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 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).

Adolescent↗