Stereology is a set of simple and efficient methods for quantitation of three‐dimensional microscopic structures which is specifically tuned to provide reliable data from sections. Within the last few years, a number of new methods has been developed which are of special interest to pathologists. Methods for estimating the volume, surface area and length of any structure are described in this review. The principles on which stereology is based and the necessary sampling procedures are described and illustrated with examples. The necessary equipment, the measurements, and the calculations are invariably simple and easy.

M. J. The new stereological tools: Disector, fractionator, nucleator and point sampled intercepts and their use in pathological research and diagnosis. APMIS 96: 857-881, 1988.The new stereological methods for correct and efficient sampling and sizing of cells and other particles are reviewed. There is a hierarchy of methods starting from the simplest where even the microscopic magnification may be unknown to the most complex where typically both section thickness and the magnification must be known. Optical sections in suitably modified microscopes can be used to improve the ease and speed with which even the most demanding of these methods are performed. The methods are illustrated by practical examples of applications to a wide range of histological entities including synapses, neurons and cancer cells, glomerular corpuscles and ovarian follicles.

Estimates of total number of different neuron and glial cell types in the dentate nuclei and the four major regions of the human cerebellum were obtained by new stereological methods. With the optical disector and Cavalieri methods, the total number of neurons and glial cells in the human cerebellum of five elderly men was estimated to be 105,000 x 10(6) (coefficient of variation, CV = 0.13). Of this total, the granule cells comprised 101,000 x 10(6) (CV = 0.13) and the Purkinje cells comprised 30.5 x 10(6) (CV = 0.13) of the neurons. The mean of the total number of neurons in the dentate nucleus was 5.01 x 10(6) (CV = 0.28). The average surface area of the human cerebellum was estimated to be 1160 cm2 (CV = 0.29). The rationale for the different sampling schemes used to quantify the various cell types is described.

Objective: Inflammatory mediators are increased in autoimmune diseases and may activate microglia and might cause an inflammatory state and degeneration of dopaminergic neurons in the brain. Thus, we evaluated whether having an autoimmune disease increases the risk for developing Parkinson disease (PD). Methods: A population based case-control study was conducted in Denmark of 13,695 patients with a primary diagnosis of PD recorded in the Danish National Hospital Register during the period 1986-2006. Each case was matched on year of birth and sex to 5 population controls selected at random from among inhabitants of Denmark who were alive at the date of the patient's diagnosis. The main exposure measure was a hospital diagnosis of 1 of 32 selected autoimmune diseases recorded 5 or more years before the index date in the files of the Danish Hospital Register. Results: We observed no overall association between a diagnosis of autoimmune disease and risk for subsequent PD (odds ratio 0.96, 95% confidence interval 0.85-1.08). In a subgroup of patients with autoimmune diseases with systemic involvement, primarily rheumatoid arthritis, we saw a decrease in risk for PD of 30%. Conclusions: Our results do not support the hypothesis that autoimmune diseases increase the risk for Parkinson disease. The decreased risk observed among patients with rheumatoid arthritis might be explained by underdiagnosis of movement disorders such as Parkinson disease in this patient group or by a protective effect of the treatment with anti-inflammatory drugs over prolonged periods. Neurology ® 2009;73:1462-1468 GLOSSARY CI ϭ confidence interval; COPD ϭ chronic obstructive pulmonary disease; ICD-8 ϭ International Classification of Diseases, 8th revision; NSAID ϭ nonsteroidal anti-inflammatory drug; OR ϭ odds ratio; PD ϭ Parkinson disease. Parkinson disease (PD) is a movement disorder that exhibits clinically signs of rigidity, bradykinesia, postural instability, and tremor, as well as a large number of nonmotor features, including dementia and depression. 1,2 The patient's brain characteristically lacks the neurotransmitter dopamine because of the deaths of dopaminergic neurons. The etiology of the disease is largely unknown, except that a small percentage of younger-onset cases are caused by rare genetic mutations. 3 One hypothesis is that inflammatory mediators activate immune cells in the brain (microglia), which may cause or contribute to the degeneration of neurons. 4 Patients with autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus, produce chronically high concentrations of inflammatory mediators over long periods of time, 5 and it has been hypothesized that these patients may be at increased risk for neurodegenerative diseases such as PD. 6-8 This hypothesis is supported by studies on brains taken postmortem from parkinsonian patients that demonstrated increased levels of proinflammatory mediators and apoptosis-related proteins in the striatal dopaminergic regions of the brain. 9-11 However, it was uncl...

Objective To determine whether a hospital contact for a head injury increases the risk of subsequently developing Parkinson’s disease.Design Population based case-control study.Setting Denmark.Participants 13 695 patients with a primary diagnosis of Parkinson’s disease in the Danish national hospital register during 1986-2006, each matched on age and sex to five population controls selected at random from inhabitants in Denmark alive at the date of the patient’s diagnosis (n=68 445).Main outcome measures Hospital contacts for head injuries ascertained from hospital register; frequency of history of head injury.Results An overall 50% increase in prevalence of hospital contacts for head injury was seen before the first registration of Parkinson’s disease in this population (odds ratio 1.5, 95% confidence interval 1.4 to 1.7). The observed association was, however, due almost entirely to injuries that occurred during the three months before the first record of Parkinson’s disease (odds ratio 8.0, 5.6 to 11.6), and no association was found between the two events when they occurred 10 or more years apart (1.1, 0.9 to 1.3).Conclusions The steeply increased frequency of hospital contacts for a head injury during the months preceding the date at which Parkinson’s disease was first recorded is a consequence of the evolving movement disorder rather than its cause.