Lene Werdelin

Lower urinary tract symptoms and bladder control in advanced Parkinson's disease : Effects of deep brain stimulation in the subthalamic nucleus

Deep brain stimulation in the subthalamic nucleus (STN) leads to significant improvement in motor function in patients with advanced Parkinsons disease (PD). In this prospective study including 16 patients with PD, we investigated (1) lower urinary tract symptoms (LUTS) by questionnaires International Prostate Symptom Score (IPSS, symptoms only) and Danish Prostate Symptom Score (DanPSS, symptoms and bother of symptoms) and (2) bladder control (assessed by urodynamics) before and after implantation of electrodes in the STN. PD symptoms (Unified Parkinsons Disease Rating Scale score) improved significantly (P < 0.0001), and symptoms of overactive bladder (IPSS) decreased along with the troublesome symptoms of overactive bladder (DanPSS; P < 0.01 for both). Urodynamic parameters before and after implantation of electrodes in the STN, evaluated with and without the stimulation on, did not change significantly.

Clinical impact of diagnostic SPET investigations with a dopamine re-uptake ligand

Abstract. The diagnosis of Parkinsons disease is based on clinical features with pathological verification. However, autopsy has been found to confirm a specialist diagnosis in only about 75% of cases. Especially early in the course of the disease, the clinical diagnosis can be difficult. Imaging of presynaptic dopamine transporters (DAT receptors) has provided a possible diagnostic probe in the evaluation of Parkinsons disease. The cocaine analogue [123I]-2-β-carboxymethoxy-3-β(4-iodophenyl)tropane ([123I]-β-CIT) is one of several radioligands that have been developed for single-photon emission tomography (SPET). The purpose of this study was to evaluate the impact of [123I]-β-CIT SPET on the diagnosis and clinical management of patients with a primary, tentative diagnosis of parkinsonism. We undertook a retrospective evaluation of the clinical records of 90 consecutive patients referred to [123I]-β-CIT SPET from the neurological department, Bispebjerg Hospital. In 58 subjects the scans revealed altered tracer uptake consistent with Parkinsons disease, progressive supranuclear palsy and multiple system atrophy. A significant change in the management or treatment because of the scan was found in 25 patients (28%). The sensitivity of the examination was 97% and the specificity 83%. In conclusion, a significant clinical impact of DAT receptor SPET imaging was found. DAT receptor imaging is a useful diagnostic probe in patients with a possible diagnosis of parkinsonism.

Oromandibular dystonia involving the lateral pterygoid muscles: four cases with different complexity.

The report describes oromandibular dystonia (OMD) in four women with involuntary activity of the lateral pterygoid muscles (LP), causing incapacitating protrusive and lateral jaw movements and displacements, and treatment with botulinum toxin type A (BTX). For initial survey and treatment control, OMD was analyzed with several, independent, and standardized methods. OMD severity and functional difficulties were evaluated subjectively and scored from videotapes. Jaw movements were assessed graphically with a magnetic tracking system, and electromyographical activity (EMG) of LP was recorded with needle electrodes using an intraoral approach, whereas activity of masseter muscles was recorded with surface electrodes. EMG‐guided BTX injections (25–40 units Botox per muscle) into the muscles were performed with cannula electrodes. Compared with reference values for LP, OMD was associated with a markedly increased level of spontaneous activity, but almost normal level of maximum voluntary activity. The central pattern generator for mastication seemed to override the dystonic activity, as all patients were able to chew despite some distortion. BTX reduced both the spontaneous and the maximum activity for 3–9 months. Concomitantly, a marked reduction of the OMD severity, mandibular movements and functional disturbances were also present with the best effect in localized OMD with late onset.

Inherited and de novo mutations in sporadic cases of DYT1-dystonia.

A study of Danish probands with primary torsion dystonia is presented. The probands were examined clinically and biochemically to exclude secondary dystonia. Mutation analyses for the GAG-deletion in the DYT1 gene were performed on 107 probands; and the mutation was detected in three. All three probands had the classical phenotype of DYT1-dystonia, but only one had a family history of dystonia. The other two probands had, obviously, sporadic DYT1-dystonia, one of which was caused by a de novo mutation, while the other one had a parent being an asymptomatic carrier. De novo mutations in the DYT1 gene are seldomly reported although independent founder mutations are known to have occurred. The frequency of DYT1-dystonia was low in our study even though several probands had early onset generalised dystonia. None of the probands in our study with other types of dystonia had the GAG-deletion as reported in other studies. The difficulties in genetic counselling concerning the heterogeneity of dystonia examplified by DYT1-dystonia are outlined.

Free-living energy expenditure reduced after deep brain stimulation surgery for Parkinson's disease.

Background:  The clinical picture in Parkinson’s disease (PD) is characterized by bradykinesia, rigidity, resting tremor and postural instability. In advanced stages of the disease, many patients will experience reduced efficacy of medication with fluctuations in symptoms and dyskinesias. Surgical treatment with deep brain stimulation in the subthalamic nucleus (STN‐DBS) is now considered the gold standard in fluctuating PD. Many patients experience a gain of weight following the surgery. The aim of this study was to identify possible mechanisms, which may contribute to body weight gain in patients with PD following bilateral STN‐DBS surgery.

Human CCS gene: genomic organization and exclusion as a candidate for amyotrophic lateral sclerosis (ALS)

BackgroundAmyotrophic lateral sclerosis (ALS) is a progressive lethal disorder of large motor neurons of the spinal cord and brain. In approximately 20% of the familial and 2% of sporadic cases the disease is due to a defect in the gene encoding the cytosolic antioxidant enzyme Cu, Zn-superoxide dismutase (SOD1). The underlying molecular defect is known only in a very small portion of the remaining cases and therefore involvement of other genes is likely. As SOD1 receives copper, essential for its normal function, by the copper chaperone, CCS (Copper Chaperone for SOD), we considered CCS as a potential candidate gene for ALS.ResultsWe have characterized the genomic organization of CCS and determined exon-intron boundaries. The 823 bp coding region of the CCS is organized in 8 exons. We have evaluated involvement of the CCS in ALS by sequencing the entire coding region for mutations in 20 sporadic ALS patients.ConclusionsNo causative mutations for the ALS have been detected in the CCS gene in 20 sporadic ALS patients analyzed, but an intragenic single nucleotide polymorphism has been identified.

Proteomic investigations of the ventriculo-lumbar gradient in human CSF

Cerebrospinal fluid (CSF) is an ideal biological material in which to search for new biomarkers for improved diagnosis of neurological diseases. During a lumbar puncture between 5 and 15 mL of CSF are obtained. Previous studies have assessed the ventriculo-lumbar concentration gradient of a number of specific proteins. In the present study we took a proteomics approach to investigate the possible concentration gradient of a panel of proteins and peptides in the CSF of 16 patients with neurodegenerative diseases. Using two different mass spectrometry techniques, matrix assisted laser desorption ionization time of flight (MALDI-TOF) and surface enhanced laser desorption ionization time of flight (SELDI-TOF), we found that only one of the investigated proteins, apolipoprotein CI, was significantly decreased between the 1st and the 10th mL of CSF. Furthermore, we confirmed previous results showing a significant decrease in albumin concentration from the first to the last CSF aliquots. In conclusion, we found a significant gradient effect for only two of the measured proteins. However, a standardized procedure for CSF collection for diagnostic and research purposes is crucial to allow comparisons of results between patient groups and between laboratories. This is especially important since CSF is usually collected at several centres and variation in sampled CSF due to pre-analytical factors could complicate the interpretation of the results.

Somatosensory input and oromandibular dystonia

Oromandibular dystonia (OMD) involving the lateral pterygoid uscles (LPs) may cause incapacitating protrusive and lateral jaw ovements, but can be alleviated with botulinum toxin (BTX) [1]. ystonia is thought to be derived from dysfunction of the basal anglia, and the excess movement to be due to loss of inhibitory otor control. Neurophysiologic and neuroimaging studies have hown abnormalities at cortical and subcortical levels, probably eflecting a dysfunction in the basal ganglia-thalamo-cortical ciruits. Although dystonia is mainly a motor problem, observations uggest a sensory component with impaired inhibitory integration f somatosensory inputs at spinal, subcortical and cortical levels o ongoing motor programs [2]. Sensory tricks involving tactile timulation alleviate symptoms in dystonia, also indicate a sensory nfluence. Further, an abnormal sensorimotor integration has been roposed. In its control of orofacial motor functions the face priary motor area (face MI) of the cerebral cortex utilises input from ace and mouth relayed in part via the face primary somatosenory area (face SI). Thus, afferent information and neuronal activity n the face SI assists in modulating orofacial motor functions, and europlastic changes in the face sensorimotor cortex may lead to ysfunctions [3].