Phosphodiesterase-1b deletion confers depression-like behavioral resistance separate from stress-related effects in mice.

Phosphodiesterase-1b (Pde1b) is highly expressed in striatum, dentate gyrus, CA3 and substantia nigra. In a new Floxed Pde1b × CreCMV global knockout (KO) mouse model, we show an immobility-resistance phenotype that recapitulates that found in constitutive Pde1b KO mice. We use this new mouse model to show that the resistance to acute stress-induced depression-like phenotype is not the product of changes in locomotor activity or reactivity to other stressors (learned helplessness, novelty suppressed feeding or dexamethasone suppression), and is not associated with anhedonia using the sucrose preference test. Using tamoxifen inducible Cre, we show that the immobility-resistant phenotype depends on the age of induction. The effect is present when Pde1b is Reduced from conception, P0 or P32, but not if reduced as adults (P60). We also mapped regional brain expression of PDE1B protein and of the Cre driver. These data add to the suggestion that PDE1B may be a target for drug development with therapeutic potential in depression alone or in combination with existing antidepressants.

Sacral nerve stimulation as an option for the treatment of faecal incontinence in patients suffering from cauda equina syndrome.

STUDY DESIGN: Retrospective clinical study with 1-year follow-up. OBJECTIVES: Treatment of faecal incontinence by permanent sacral nerve stimulation (SNS) in patients suffering from cauda equina syndrome (CES). SETTING: Klosterneuburg, Austria. BACKGROUND AND PURPOSE: A flaccid paresis of the sphincter ani muscle and the pelvic floor combined with faecal incontinence can occur in patients suffering from CES as a result of a trauma in the region of the lumbar spine. If the incontinence cannot be managed by the use of laxatives or anal tampons, the patient is restricted in his/her quality of life. Thus, it was our aim to improve sphincter function and anal sensitivity to achieve voluntary rectal defaecation. MATERIALS AND METHODS: The functional integrity of at least one sacral root (S2-S4) was determined through percutaneous nerve evaluation (PNE). Following this analysis, a period of external temporary SNS was performed to evaluate the functional effect. If there was a decrease in the number of episodes of faecal incontinence during this evaluation period, a neurostimulation device (InterStim; Medtronic) was implanted. PATIENTS: A total of 11 patients suffering from flaccid paresis of the anal sphincter muscle and faecal incontinence caused by CES underwent PNE, which was successful in 8 patients. Two of these patients were eliminated from the procedure at the end of the temporary SNS period, one patient refused the permanent implantation. Therefore, five patients proceeded to permanent implantation, which led to an improved continence in all the cases. DISCUSSION: In the synopsis of the preoperative proctologic and neurological findings, successful electric stimulation of the sacral roots can be expected in incomplete CES. In the case of flaccid paresis of the anal sphincter muscles caused by an incomplete CES, permanent SNS offers a promising option for the treatment of faecal incontinence. .

[Etiology of Alzheimer's disease]. / Zur Atiologie der Alzheimer-Krankheit.

The major factor that causes problems in studies on the aetiology of Alzheimer's disease (AD) is the clinical heterogeneity of the condition. Familial early-onset AD and familial late-onset AD are differentiated from sporadic AD. Aetiologically a genetic defect on chromosome 21 is the most important factor, at least in some cases of AD. In familial AD and autosomal dominant inheritance with complete penetrance in old age is thought to be possible. In sporadic AD the role of genetic and exogenous factors (infectious agents, aluminium) is unknown. The current status of knowledge about the aetiology of Alzheimer's disease is reviewed with reference to the literature.

[Depression, nonverbal intellectual impairment and quality of life following left-brain ischemic insult--results of a catamnestic study]. / Depression, nichtsprachliche intellektuelle Beeinträchtigung und Lebensqualität nach linkshirnigem ischämischen Insult--Ergebnisse einer katamnestischen Studie.

The purpose of the present study was to establish the relationship between persisting aphasia and the extent of overall disability in the long-term outcome following left hemisphere ischaemic stroke. 55 right-handed patients who had sustained an initial left-sided cerebral infarction, verified by CT scan, were investigated after a mean observation period of six years. 39 patients were categorized as being non-aphasic, and 16 as being aphasic (3 Global, 6 Broca's, 1 conduction, 1 transcortical motor and 5 anomic aphasics) at the end of the follow-up period. Regarding motor and sensory functions, a correlation between the presence of aphasia and the severity of deficits could be established at the end of the follow-up period. With respect to activities of daily living, a significantly larger number of aphasic stroke victims had to rely on help by others. Furthermore, the persistence of aphasia also negatively influenced the subsequent occupational capacity. With regard to social participation and leisure activities, a significant reduction was found in aphasic long-term stroke survivors as compared to non-aphasics. Concerning quality of life, both groups reported a marked decline at the end of the observation period; the presence of aphasia had an additional negative effect. However, as regards the long-term non-verbal cognitive impairment, statistical analysis revealed no significant differences between both groups. In addition, aphasic stroke survivors did not demonstrate a higher incidence of depressive states than those without language deficit. On the basis of our results it is concluded that the presence of aphasia in left-hemispheric ischaemic stroke survivors indicates a more severe stroke, resulting in greater physical disability and social handicap in the long-term outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

Galanthamine treatment in Alzheimer's disease.

18 patients who had fulfilled the NINCDS-ADRDA criteria for "possible AD" took part in a clinical study to evaluate the effect of the cholinesterase inhibitor Galanthamine, 30 mg/day. Neuropsychological und social parameters were rated. This open clinical pilot-study showed no statistic significant change in neuropsychological test-results. However after 1 year treatment 6 patients are still taking the drug. According to their care-persons there was a positive changes in competence of everyday-routine and/or in the emotional situation.

Clinical comparison of dementia in Parkinson's and Alzheimer's disease.

Neuropsychological, neuropathological and neurochemical findings show different types of dementias. Few of them have been able to confirm a division into "subcortical" and "cortical" dementia, so this concept has to be questioned. The present clinical study compared type and severity of dementia in 12 Parkinson-patients (PD) and 12 Alzheimer-patients (AD). The age-adjusted normal value differed a significantly from both patient groups. No significant difference in pattern of neuropsychological deficits between PD- and AD-patients was apparent. However, after similar duration of illness, dementia was more severe in AD- than in PD-patients.

[Prognosis and documentation of the disease course in severe craniocerebral injuries]. / Zur Verlaufsprognose und -dokumentation von schweren Schädelhirnverletzungen.

35 survivors of severe head injury were consecutively admitted to the Neurological Department, University of Vienna for early rehabilitation. The outcome after a mean observation periods of 19 months was compared with clinical signs (best motor response, pupillary light reaction, pupil size) in the acute stage. The clinical signs were graded semiquantitatively. The outcome was assessed using the Glasgow Outcome Scale and compared with alternatives, the Karnofsky Performance Status and a self-designed neuropsychological rating scale. Both indexes appeared to possess certain advantages which included additional information and sensitivity to change. A significant correlation was established between the long-term outcome after severe head injury on the one hand and the "best motor response" and changes in pupillary light reaction in the acute stage on the other hand. However, the clinical parameter of pupil size in the acute stage does not provide a prognostic indicator of the disability status at the end of the observation period. There was good agreement between the outcome scores derived by means of the 3 rating scales. Solely with respect to the items "orientation and memory function" and "emotions" of the neuropsychological rating scale was no significant correlation obtained with the clinical sign "best motor response" in the acute stage. Our results indicate that it seems possible to assess the outcome after severe head injury not only be means of the widely-adopted Glasgow Outcome Scale, but also using the Karnofsky Performance Status and our neuropsychological rating scale without any marked loss of reliability. The clinical signs - "best motor response" and pupillary light reaction - are excellent prognostic indicators of the long-term outcome after severe head injury.