Development of weakness in patients with chronic inflammatory demyelinating polyneuropathy and only sensory symptoms at presentation: A long-term follow-up study

This long-term follow-up study examined patients with chronic inflammatory demyelinating polyneuropathy (CIDP) and only sensory symptoms at first presentation, with emphasis on the development of motor symptoms and long-term disability. From all CIDP patients referred to our Department between 1987 and 1995, seven had only sensory symptoms at first clinical presentation. These were investigated according to a standard protocol, including a quantified clinical neurological examination and nerve conduction studies. The mean duration of the disease before weakness developed was 3.1 years, but varied considerably (0.8–6.3 years). At follow-up, weakness developed in five patients and persisted in three of them. Five patients were not seriously incapacitated by their disease (Rankin 1 or 2), four of them being in remission now and one showing a very slow progression of disease. Two patients were moderately disabled (Rankin 3); one had severe persistent sensory ataxia and only weakness during relapses and one had stepwise progression and moderate weakness. Motor nerve conduction studies revealed that the most notable worsening in the entire group of patients was a decrease in distal compound muscle action potential amplitudes, indicating the development of distal conduction block or axonal degeneration. These findings show that CIDP with only sensory symptoms is a transient clinical stage that precedes the appearance of weakness in about 70% of patients. The long-term prognosis does not differ from that of patients with CIDP who have weakness at the beginning of the disease. Received: 3 December 1998 Received in revised form: 17 May 1999 Accepted: 2 July 1999     

Sacral electrical neuromodulation as an alternative treatment option for lower urinary tract dysfunction

Temporary electrical stimulation using anal or vaginal electrodes and an external pulse generator has been a treatment modality for urinary urge incontinence for nearly three decades. In 1981 Tanagho and Schmidt introduced chronic electrical stimulation of the sacral spinal nerves using a permanently implanted sacral foramen electrode and a battery powered pulse generator for treatment of different kinds of lower urinary tract dysfunction, refractory to conservative treatment. At our department chronic unilateral electrical stimulation of the S3 sacral spinal nerve has been used for treatment of vesi-courethral dysfunction in 43 patients with a mean postoperative follow up of 43,6 months. Lasting symptomatic improvement by more than 50 % could be achieved in 13 of 18 patients with motor urge incontinence (72,2 %) and in 18 of the 21 patients with urinary retention (85,7 %). Implants offer a sustained therapeutic effect to treatment responders, which is not achieved by temporary neuromodulation. Chronic neuromodulation should be predominantly considered in patients with urinary retention. Furthermore in patients with motor urge incontinence, refusing temporary techniques or in those requiring too much effort to achieve a sustained clinical effect. Despite high initial costs chronic sacral neuromodulation is an economically reasonable treatment option in the long run, when comparing it to the more invasive remaining therapeutic alternatives.     

Spatiotemporal distribution of dying neurons during early mouse development

Apoptosis is a critical cellular event during several stages of neuronal development. Recently, we have shown that biotinylated annexin V detects apoptosis in vivo in various cell lineages of a wide range of species by binding to phosphatidylserines that are exposed at the outer leaflet of the plasma membrane. In the present study, we tested the specificity by which annexin V binds apoptotic neurons, and subsequently investigated developmental cell death in the central and peripheral nervous system of early mouse embryos at both the cellular and histological level, and compared the phagocytic clearance of apoptotic neurons with that of apoptotic mesodermal cells. Our data indicate: (i) that biotinylated annexin V can be used as a sensitive marker that detects apoptotic neurons, including their extensions at an early stage during development; (ii) that apoptosis plays an important part during early morphogenesis of the central nervous system, and during early quantitative matching of brain-derived neurotrophic factor and neurotrophic factor 3 responsive postmitotic large clear neurons in the peripheral ganglia with their projection areas; and (iii) that apoptotic neurons are removed by a process that differs from classical phagocytosis of non-neuronal tissues.     

Education and the incidence of dementia in a large population-based study: the Rotterdam Study

We assessed the risk of dementia by educational level in a prospective population-based study. In the Rotterdam Study, 6,827 nondemented participants with known education level were followed for an average of 2.1 years. During this period, 137 new cases of dementia occurred. Low education was associated with higher dementia risk in women but not in men, suggesting that the association is modified by sex. Our data indicate that cross-sectional studies may overrate the association between education and risk of dementia.     

Relational support and person characteristics in adolescence

In this paper, an heuristic model of the personality characteristics of adolescents and the supportive dimensions of interactions, relationships and groups is presented. The model takes the concept of developmental tasks as its starting point and it is assumed that developmental tasks can be characterized in terms of four modalities: intentions, behaviour, cognitions and affect. The same four modalities can also be used to characterize dimensions of personality and aspects of interactional and relational support. The results of several empirical studies are presented to illustrate the model. Together, these studies present a transactional picture of the personality of adolescents and their relationships in which personality and relationships influence each other and jointly determine psychosocial functioning.     

Epinephrine-induced panic attacks and hyperventilation

To assess the effects of epinephrine on ventilation in patients with panic disorder and in social phobics, analyses were performed on pooled data from two previous infusion studies. Throughout the infusion, changes in transcutaneous PCO2 (tcPCO2), subjective anxiety, heart rate and blood pressure were recorded continuously. Twenty-nine patients received epinephrine, ten patients received placebo. Thirteen patients (45%) had a panic attack during epinephrine. The fall in tcPCO2 and the cardiovascular response was greater in panicking patients than patients who did not panic. Although the fall in tcPCO2 associated with panic was not substantial and did not indicate clinically significant acute hyperventilation, it appears to be a sensitive index for epinephrine-induced panic. The fall in tcPCO2 was predicted rather by the frequency of occurrence of anxiety-related somatic symptoms than by the fear of these symptoms. These findings further reduce a role for fear of bodily sensations in epinephrine-induced panic attacks and favor a biological sensitivity to sympathetic stimulation.     

Endoneurial microvascular abnormalities of sural nerve in non-diabetic chronic atherosclerotic occlusive disease

Neuropathic abnormalities are found in chronically ischaemic limbs associated with non-diabetic atherosclerotic peripheral vascular disease (PVD). In chronic ischaemic neuropathy, microvascular alterations play a key role in its development. We undertook morphometric assessment of endoneurial microvessels in the sural nerves, taken from severely ischaemic amputated legs in nine chronic non-diabetic PVD. These subjects had threatened ischaemic limbs and revealed clinical, physiological and pathological evidence of neuropathy. For comparison, sural nerves taken from amputated legs due to non-ischaemic disorders (n=4) and chronic PVD associated with diabetes (n=3) were also assessed. We evaluated the areas of vascular lumen, endothelial cells and whole vessel, as well as the percentage of closed capillaries. Endothelial area of sural nerve microvessels in non-diabetic PVD nerves was significantly greater than in non-ischaemic control nerves. Periendothelial cell area containing pericytes and basement membranes was also significantly increased in non-diabetic PVD nerves when compared with control nerves. Vascular lumen area was significantly less in non-diabetic PVD nerves than in non-ischaemic control nerves. Endoneurial microvessels in diabetic PVD nerves showed similar results: thickened vessel wall and smaller lumen. Periendothelial area in diabetic nerves was significantly greater than in non-diabetic PVD nerves. We demonstrated swollen endothelial cells and increased periendothelial area associated with narrowed lumen in sural nerve endoneurial microvessels of severe chronic PVD. Basement membrane reduplication of endoneurial capillaries was seen in non-diabetic PVD nerves. These microvascular abnormalities could play an important role in the development of chronic ischaemic neuropathy in PVD limbs.     

Genetic and environmental factors in Alzheimer's disease

In recent years, considerable progress has been made in unraveling the etiology of Alzheimer's disease (AD). Dominant mutations have been identified, in the beta-amyloid precursor protein gene (APP), and in two homologous genes presenilin 1 (PSEN-1) and presenilin 2 (PSEN-2). The contribution of these mutations to the occurrence of AD in the general population is estimated to be lower than 1p. 100. A genetic risk factor of more importance on the population level is the Apolipoprotein E (APOE) gene that may explain up to 17p. 100 of the prevalence of AD in the general population. It is clear that other yet unknown genes must be involved in the etiology of AD. Two loci on chromosome 12 have been suggested, but no consistent effect could be found. Important progress with regard to non-genetic risk factors concerns the role of vascular and endocrine factors in the pathogenesis. Of major interest for the prevention of AD will be the interaction of genetic and non-genetic risk factors. Large scale, long term follow-up studies, ongoing at present, may clarify this issue.