Climbing fiber development: do neurotrophins have a part to play?

The climbing fiber input to the cerebellum is crucial for its normal function but those factors which control the development of this precisely organized pathway are not fully elucidated. The neurotrophins are a family of peptides, which have many roles during development of the nervous system, including the cerebellum. Since the cerebellum and inferior olive express neurotrophins and their receptors, we propose that neurotrophins are involved in the regulation of climbing fiber development. Here we review the temporo-spatial expression of neurotrophins and their receptors at key ages during climbing fiber development and then examine evidence linking neurotrophins to climbing fiber development, including some of the intracellular pathways involved. During prenatal development the expression of neurotrophins in the hindbrain coupled with their function in neurogenesis and migration, is consistent with a role of NT3 in inferior olivary genesis. Subsequently, cerebellar expression of two neurotrophins, NT3 and NT4, is concurrent with olivary receptor expression and the time of olivary axonal outgrowth and this continues postnatally during early climbing fiber synaptogenesis on Purkinje cells. The expression-pattern of neurotrophins changes with age, with falling NGF, NT3 and NT4 but increasing granule cell BDNF. Importantly, olivary expression of neurotrophin receptors, and therefore climbing fiber responsiveness to neurotrophins, falls specifically during maturation of the climbing fiber-Purkinje cell synapse. The function of BDNF is less certain, but experimental studies indicate that it has a role in climbing fiber innervation of Purkinje cells, particularly synaptogenesis and synaptic plasticity. Its importance is highlighted by the overlap of BDNF signalling with several cellular pathways, which regulate climbing fiber maturation. From the data presented, we propose not only that neurotrophins are involved in climbing fiber development, but also that several act in a specific temporal order.     

Smoking, alcohol, and coffee consumption preceding Parkinson's disease: a case-control study

OBJECTIVE: To study the association of PD with preceding smoking, alcohol, and coffee consumption using a case-control design. METHODS: The authors used the medical records linkage system of the Rochester Epidemiology Project to identify 196 subjects who developed PD in Olmsted County, MN, during the years 1976 to 1995. Each incident case was matched by age (+/-1 year) and sex to a general population control subject. The authors reviewed the complete medical records of cases and control subjects to abstract exposure information. RESULTS: For coffee consumption, the authors found an OR of 0.35 (95% CI = 0.16 to 0.78, p = 0.01), a dose-effect trend (p = 0.003), and a later age at PD onset in cases who drank coffee compared with those who never did (median 72 versus 64 years; p = 0.0002). The inverse association with coffee remained significant after adjustment for education, smoking, and alcohol drinking and was restricted to PD cases with onset at age <72 years and to men. The OR for cigarette smoking was 0.69 (95% CI = 0.45 to 1.08, p = 0.1). The authors found no association between PD and alcohol consumption. Extreme or unusual behaviors such as tobacco chewing or snuff use and a diagnosis of alcoholism were significantly more common in control subjects than cases. CONCLUSIONS: These findings suggest an inverse association between coffee drinking and PD; however, this association does not imply that coffee has a direct protective effect against PD. Alternative explanations for the association should be considered.     

Bispectral index monitoring of sedation during endoscopy

BACKGROUND: No objective measure of the level of sedation is universally accepted. However, bispectral index monitoring is currently used to objectively measure sedation levels in several clinical settings. This study compares the temporal relationship of bispectral index levels versus the Observer's Assessment of Alertness/Sedation (OAA/S) scale for sedation during endoscopy and proposes a functional bispectral index range for endoscopic procedures. METHODS: Fifty consecutive adults undergoing endoscopic retrograde cholangiopancreatography, colonoscopy, or esophagogastroduodenoscopy by a single endoscopist were studied. Intravenous sedation was achieved with diazepam and meperidine. Bispectral index levels (0 to 100) and OAA/S scores (1 to 5) were recorded every 3 minutes by a single trained observer. RESULTS: There were significant temporal correlations between bispectral index levels and OAA/S scores (r = 0.59, p < 0.0001). Bispectral index levels and OAA/S scores corresponded with the need for additional sedation as determined clinically by the endoscopist. An OAA/S score of 3 corresponded to a bispectral index level of 81.49 +/- 9.78. CONCLUSIONS: Bispectral index monitoring temporally correlates with the OAA/S scale and therefore provides an objective measure of sedation during endoscopy. This preliminary, observational study suggests that a bispectral index level near 82 corresponds with sufficient and functional sedation levels for endoscopy.     

Profile of families with parkinsonism-predominant spinocerebellar ataxia type 2 (SCA2).

Spinocerebellar ataxia type 2 (SCA2) has been recognized recently as an uncommon cause of parkinsonism, an alternate presentation to the typical cerebellar disorder. This research review summarizes the existing literature on parkinsonism-predominant presentation SCA2 and presents new clinical cases of patients with this condition. Various phenotypes are noted in this subtype of SCA2, including parkinsonism indistinguishable from idiopathic Parkinson's disease (PD), parkinsonism plus ataxia, motor neuron disease, and postural tremor. In several kindreds with multiple affected family members, the SCA2 expansion segregated with disease; in addition, several single cases of parkinsonism with and without a family history are also described. The number of repeats in symptomatic patients ranged from 33 to 43. Interruption of the CAG repeat with CAA, CGG, or CCG was found in some individuals, possibly stabilizing the repeat structure and accounting for the relative stability of the repeat size across generations in some families; allele length is not necessarily indicative of trinucleotide repeat architecture. Positron emission tomography scanning in one family showed reduced fluorodopa uptake and normal to increased raclopride binding with a rostrocaudal gradient similar to that found in idiopathic PD. This review emphasizes the importance of testing for SCA2 in patients with parkinsonism and a family history of neurodegenerative disorders. Testing for SCA2 is also important in studies of inherited parkinsonism.