Proteinuria and other renal functions in Wilson’s disease

Renal lesions have repeatedly been described in Wilson’s disease (WD). We investigated the excretion of total protein, albumin, low (LMW) and high molecular weight (HMW) proteins, N-acetyl-β-D-glucosaminidase (NAG), and calcium, as well as creatinine clearance, in 24-h urine samples of 41 patients with WD aged 6 – 37 (mean 17) years who had been treated for a period of 0 – 15 (mean 4.5) years with D-penicillamine (900 mg/day). The amount of all protein excreted was significantly increased compared with controls, 39% of patients presenting with total proteinuria more than two standard deviations from the mean of controls. The changes in protein excretion depended on the duration of treatment. LMW proteinuria was elevated almost exclusively in the first 2 years after the start of treatment, indicating early tubular damage. This is supported by an initially high excretion of β₂-microglobulin, NAG, and calcium. Increased excretion of HMW proteins, including albumin, persisted over longer periods, which suggests glomerular injury in some patients, possibly related to the use of D-penicillamine. Creatinine clearance remained roughly within normal limits. We propose that renal function should regularly be checked in patients with WD. Received October 26, 1995; received in revised form August 27, 1996; accepted September 20, 1996     

Perioperative respiratory events in smokers and nonsmokers undergoing general anaesthesia

Background: The prevalence of respiratory diseases in smokers and nonsmokers and the incidence of perioperative respiratory events (PREs) were investigated for patients undergoing general anaesthesia. The aim was to quantify well-known problems and to identify possible new associations between smoking and PREs.
Methods: From July 1992 to December 1994, risk factors, demographic data, and PREs were documented by an automatically readable anaesthetic record (ARAR). PREs were used as defined by the German Society of Anaesthesiology and Intensive Care.
Results: Of 26 961 subsequent anaesthesias in adults, 7122 (26.4%) were performed in smokers with a prevalence of chronic bronchitis of 23.3% (4.8% in nonsmokers). 1573 PREs occurred in 1397 (5.2%) of all anaesthetics. 459 events concerned intubation problems and problems in technical airway management. 1114 specific respiratory events (SPREs) like re-intubation, laryngospasm, bronchospasm, aspiration, hy-poventilation/hypoxaemia and others had a total incidence of 5.5% in smokers and 3.1% in nonsmokers. The relative risk (RR) of SPREs was 1.8 in all smokers, 2.3 in young (16–39 years) smokers, and 6.3 in obese young smokers. The RR of perioperative bronchospasm was 25.7 in young smokers with chronic bronchitis.
Conclusion: The impact of smoking on perioperative respiratory problems should make anaesthetists take this widespread preoperative condition seriously, particularly in young adults. The presented method of incident reporting (based on a national classification) could contribute to future research in anaesthetic epidemiology.     

Effects of epidermal growth factor in the mammalian central nervous system: Its possible implications in brain pathologies and therapeutic applications

The development and maintenance of the normal functional integrity of the mammalian central nervous system is under the influence of a number of growth and trophic factors. One such growth factor, epidermal growth factor, has been detected in the mammalian brain and found to be associated with various brain regions and cell types. This small ubiquitous polypeptide can influence the proliferation, Metabolism, and differentiation of both glia and neurons in the central nervous system. We discuss the effects of epidermal growth factor on glial and neuronal cell function in an attempt to understand its role in development and maintenance of normal brain integrity. In addition, we review its possible implications in several pathological states in the central nervous system and speculate on therapeutic applications for this growth factor. © 1992 Wiley-Liss, Inc.     

Suggestive linkage to chromosome 19 in a large Cuban family with late‐onset Parkinson's disease

The identification of disease genes using family‐based approaches has provided important insights into the pathogenesis of Parkinson's disease (PD) demonstrating the importance of genetic studies on monogenic forms of the disease. We studied a large Cuban family with typical, late‐onset PD and probable autosomal dominant inheritance. Mean age at onset was 61.2 years (±12.53, 45–76). Other phenotypes such as essential tremor and atypical parkinsonism were observed in this family. We carried out a genome‐wide scan and linkage analyses. The genetic data were analyzed using a conservative model in which only patients with clinically definite or likely PD were considered affected, other phenotypes were regarded as “unknown.” Multipoint analyses yielded a maximum LOD of 2.26 between markers D19S221 and D19S840. Haplotype analysis showed a region on chromosome 19 shared by six of seven PD patients. The essential tremor phenotype and the atypical parkinsonism do not segregate with this haplotype, suggesting a different etiology. Our findings suggest the presence of a novel locus for PD on chromosome 19p13.3–q12. We propose that an oligogenic model with moderate contribution of two or three genes rather than a “pure” monogenic model might explain better the wide range in age at onset, the reduced penetrance and the phenotypical variability observed in PD families. © 2003 Movement Disorder Society     

Fear of falling and postural control in Parkinson's disease.

This study investigated the relationship between fear of falling (FOF) and qualitative and quantitative postural control in Parkinson's disease (PD). Fifty-eight nondemented PD patients were studied along with age-matched healthy controls. The degree of FOF was estimated using the Activities-specific Balance Confidence scale. Qualitative postural control was evaluated using a component of the Unified Parkinson Disease Rating Scale. Postural control was quantified, using centre of pressure measures obtained from a force plate, for eight standing balance tests of different challenges. The results showed that FOF was more evident for PD patients when compared with healthy individuals of similar age. Furthermore, FOF was significantly associated with a qualitative estimate of postural control in PD; individuals with PD who had a greater degree of posture impairment reported greater FOF. The results also showed that an estimate of FOF may help to explain quantitative postural instability in PD. FOF, when coupled with a qualitative estimate of postural control, was able to explain a greater amount of variation in quantitative balance performance for five of the eight balance tests. When considered independently, the qualitative measure of postural control, in general, could not well predict quantitative balance performance. The greater degree of FOF and its possible association with altered postural control suggests that FOF should be considered as an important, independent risk factor in the assessment and treatment of postural instability in patients with PD.     

Effect of cognitive and motor tasks on postural stability in Parkinson's disease: a posturographic study.

To analyse the effect of concomitant cognitive or motor task performance on balance control in Parkinson's disease (PD), we performed a posturographic study in 24 PD patients and in 20 sex- and age-matched control subjects. Postural sway was measured with eyes open (EO) and eyes closed (EC) during quiet stance and during performance of calculation or motor sequence of thumb opposition to the other fingers. No difference of centre of foot pressure (COP) parameters was observed during quiet standing (either EO or EC) between patients and controls, but visual deprivation induced in both groups a worsening of postural stability. COP area was significantly increased in PD patients during dual task performance, whereas no difference of COP path and x-y axes was observed. The effects induced by the performance of cognitive or motor task were significantly more evident in PD patients with clinical evidence of postural instability (presence of prior falls in the history). This study demonstrates that dual task interference on postural control can be observed in PD patients during performance of cognitive as well as motor tasks. The balance deterioration during dual task performance was significantly enhanced in patients with history of prior falls. These findings have some implications for the strategies to be used in reducing the risk of fall in PD.     

Deep brain stimulation for Parkinson's disease dissociates mood and motor circuits: a functional MRI case study.

Behavioral disturbances have been reported with subthalamic (STN) deep brain stimulation (DBS) treatment in Parkinson's disease (PD). We report correlative functional imaging (fMRI) of mood and motor responses induced by successive right and left DBS. A 36-year-old woman with medically refractory PD and a history of clinically remitted depression underwent uncomplicated implantation of bilateral STN DBS. High-frequency stimulation of the left electrode improved motor symptoms. Unexpectedly, right DBS alone elicited several reproducible episodes of acute depressive dysphoria. Structural and functional magnetic resonance imaging (fMRI) imaging was carried out with sequential individual electrode stimulation. The electrode on the left was within the inferior STN, whereas the right electrode was marginally superior and lateral to the intended STN target within the Fields of Forel/zona incerta. fMRI image analysis (Analysis of Functional NeuroImages, AFNI) contrasting OFF versus ON stimulation identified significant lateralized blood oxygen level-dependent (BOLD) signal changes with DBS (P < 0.001). Left DBS primarily showed changes in motor regions: increases in premotor and motor cortex, ventrolateral thalamus, putamen, and cerebellum as well as decreases in sensorimotor/supplementary motor cortex. Right DBS showed similar but less extensive change in motor regions. More prominent were the unique increases in superior prefrontal cortex, anterior cingulate (Brodmann's area [BA] 24), anterior thalamus, caudate, and brainstem, and marked widespread decreases in medial prefrontal cortex (BA 9/10). The mood disturbance resolved spontaneously in 4 weeks despite identical stimulation parameters. Transient depressive mood induced by subcortical DBS stimulation was correlated with changes in mesolimbic cortical structures. This case provides new evidence supporting cortical segregation of motor and nonmotor cortico-basal ganglionic systems that may converge in close proximity at the level of the STN and the adjacent white matter tracts (Fields of Forel/zona incerta).     

Acute psychotropic effects of bilateral subthalamic nucleus stimulation and levodopa in Parkinson's disease.

High-frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves the motor symptoms of Parkinson's disease (PD). Opposite changes in mood, such as mania or depression, have been reported after surgery, but it is not known whether these side effects are specifically related to STN DBS. To learn whether STN DBS also influences the limbic loop, we investigated acute subjective psychotropic effects related to levodopa or bilateral STN DBS. After a median postoperative follow-up of 12 months, 50 PD patients completed the Addiction Research Center Inventory (ARCI), assessing subjective psychotropic effects in four conditions: off-drug/on-stimulation; off-drug/off-stimulation; on-drug/off-stimulation; and on-drug/on-stimulation. Both levodopa and STN DBS improved all the ARCI subscales, indicating subjective feelings of well being, euphoria, increase in motivation, and decrease in fatigue, anxiety, and tension. A suprathreshold dose of levodopa was significantly more effective than STN DBS, using the same electrical parameters as for chronic stimulation, on four of the five ARCI subscales. We concluded that 1) both STN DBS and levodopa have synergistic acute beneficial psychotropic effects in PD, 2) the psychotropic effects of both treatments need to be considered in the long-term management of chronic STN DBS, and 3) the results indicate an involvement of the limbic STN in mood disorders of PD.     

Testosterone not associated with violent dreams or REM sleep behavior disorder in men with Parkinson's.

We examined the relationship between testosterone levels, violent dreams, and REM sleep behavior disorder (RBD) in 31 men with Parkinson's disease (PD): 12 with clinical RBD and 19 without. All PD patients with clinical RBD experienced violent dreams, but none of the 19 non-RBD patients reported violent dreams. While dream content appears to be more aggressive in PD patients with clinical RBD, the presence of violent dreams or clinical RBD is not associated with testosterone levels in men with PD.     

Measurement of contact impedance of electrodes used for deep brain stimulation

High frequency electrical stimulation by means of electrodes implanted into the brain has become an accepted technique for treatment of Parkinson's disease. The electrical field distribution normally inserted into the sub thalamic nucleus minimise abnormal brain activity. Square wave pulses of 1–3.6 V with duration of 60–90 μs at a frequency range of 130–185 pps are generally used. Every electrode unit consists of four cylindrical electrodes positioned in a row and can be switched on independently. This paper determines the contact impedance of the electrodes for different frequencies and proposes improvement to reduce the contact impedance between the electrodes and the brain. Measurements were performed by placing the electrodes in a tank filled with saline. Different frequencies were applied on two electrodes via a resistor. The current was measured through the resistor and the voltage was registered between one of the electrodes and a third non current carrying electrode. The obtained values were used to calculate the contact impedance. The result shows large contact impedance for the used frequency compared to the impedance of the treated tissue, which means that variation in contact impedance can result in variation in the electrical field applied to the tissue.