Increased amoeboid microglial density in the olfactory bulb of Parkinson's and Alzheimer's patients.

The olfactory bulb (OB) is affected early in both Parkinson's (PD) and Alzheimer's disease (AD), evidenced by the presence of disease-specific protein aggregates and an early loss of olfaction. Whereas previous studies showed amoeboid microglia in the classically affected brain regions of PD and AD patients, little was known about such changes in the OB. Using a morphometric approach, a significant increase in amoeboid microglia density within the anterior olfactory nucleus (AON) of AD and PD patients was observed. These amoeboid microglia cells were in close apposition to ß-amyloid, hyperphosphorylated tau or α-synuclein deposits, but no uptake of pathological proteins by microglia could be visualized. Subsequent analysis showed (i) no correlation between microglia and α-synuclein (PD), (ii) a positive correlation with ß-amyloid (AD), and (iii) a negative correlation with hyperphosphorylated tau (AD). Furthermore, despite the observed pathological alterations in neurite morphology, neuronal loss was not apparent in the AON of both patient groups. Thus, we hypothesize that, in contrast to the classically affected brain regions of AD and PD patients, within the AON rather than neuronal loss, the increased density in amoeboid microglial cells, possibly in combination with neurite pathology, may contribute to functional deficits.

Extraforaminal ligaments of the cervical spinal nerves in humans.

BACKGROUND CONTEXT: During the last 120 years, several mechanisms to protect the spinal nerve against traction have been described. All the described structures were located inside the spinal canal proximal to the intervertebral foramen. Ligaments with a comparable function just outside the intervertebral foramen are mentioned ephemerally. No studies are available about ligamentous attachments of cervical spinal nerves to adjacent vertebrae. PURPOSE: To identify and describe ligamentous structures at each cervical level that attaches spinal nerves to structures in the extraforaminal region. STUDY DESIGN/SETTING: An anatomical study of the extraforaminal attachments of the cervical spinal nerves was performed using human spinal columns. METHODS: Five embalmed human cervical spines (C1-C8) were dissected. The extraforaminal region was dissected bilaterally to describe and measure anatomical structures and their relationships with the cervical spinal nerves. Histology was done on the ligamentous connections of nerves to the adjacent vertebral structures. RESULTS: The cervical spinal nerves are attached to the transverse process of the vertebrae. The connecting ligaments consist mainly of collagenous fibers. CONCLUSIONS: At the cervical level, direct ligamentous connections exist between extraforaminal cervical spinal nerves and nearby structures. They may serve as a protective mechanism against traction. In addition, these ligaments play an important role in the positioning of the nerves in the intervertebral foramen.

Soft tissue damage after minimally invasive THA.

BACKGROUND AND PURPOSE: Minimally invasive surgery (MIS) for hip replacement is thought to minimize soft tissue damage. We determined the damage caused by 4 different MIS approaches as compared to a conventional lateral transgluteal approach. METHODS: 5 surgeons each performed a total hip arthroplasty on 5 fresh frozen cadaver hips, using either a MIS anterior, MIS anterolateral, MIS 2-incision, MIS posterior, or lateral transgluteal approach. Postoperatively, the hips were dissected and muscle damage color-stained. We measured proportional muscle damage relative to the midsubstance cross-sectional surface area (MCSA) using computerized color detection. The integrity of external rotator muscles, nerves, and ligaments was assessed by direct observation. RESULTS: None of the other MIS approaches resulted in less gluteus medius muscle damage than the lateral transgluteal approach. However, the MIS anterior approach completely preserved the gluteus medius muscle in 4 cases while partial damage occurred in 1 case. Furthermore, the superior gluteal nerve was transected in 4 cases after a MIS anterolateral approach and in 1 after the lateral transgluteal approach. The lateral femoral cutaneous nerve was transected once after both the MIS anterior approach and the MIS 2-incision approach. INTERPRETATION: The MIS anterior approach may preserve the gluteus medius muscle during total hip arthroplasty, but with a risk of damaging the lateral femoral cutaneous nerve.

Possible nociceptive structures in the sacroiliac joint cartilage: An immunohistochemical study.

The sacroiliac joint (SI joint) is a known source of low back pain. In the absence of validated physical signs and imaging studies, the diagnosis of SI joint pain can be secured by positive response to SI joint intra-articular infiltration with local anesthetics. The current anatomical and histological knowledge concerning intra-articular structures of the sacroiliac joint is insufficient to explain the efficacy of this infiltration. Consequently, this study was undertaken to detect the intra-articular presence of substance P and calcitonin gene-related peptide (CGRP) positive nerve fibers, providing indirect evidence of nociceptive innervation of the SI joint. Free-floating sections, obtained from iliac and sacral cartilage and subchondral bone of the SI joint and adjacent ligamentous tissue, of 10 human cadavers were studied immunohistochemically. Tissue of nine human cadavers showed the presence of substance P and CGRP immunoreactivity in the superficial layer of sacral and iliac cartilage, and the surrounding ligamentous structures. Subchondral bone reacted weakly to the antisera used. These findings support the view that the SI joint may be capable of intra-articular nociception and may explain the positive response to the intra-articular deposition of local anesthetic.

Gender-related changes in increase of dopaminergic neurons in the olfactory bulb of Parkinson's disease patients.

Gender differences in dopaminergic related neurodegenerative diseases have hardly been studied until now. It is generally accepted that more men than women suffer from Parkinson's disease. One of the most prevalent symptoms in Parkinson's patients, hyposmia, does not show gender differences, while normally the sense of smell is better developed in females. Whether the change in dopamine in the olfactory bulb contributes equally to hyposmia in male and female Parkinson's patients is the subject of the present study. In a stereological study the total number of tyrosine hydroxylase immunoreactive neurons in the olfactory bulbs of male and female Parkinson's patients and age-matched controls has been estimated. The present stereological study shows that the number of tyrosine hydroxylase positive cells in control females is significantly lower than those in control males. The number of dopaminergic cells in the olfactory bulbs of both male and female Parkinson's patients equals that of healthy males of the same age group. We therefore conclude that the hyposmia in Parkinson's disease patients cannot simply be ascribed to dopamine in the olfactory bulb.

Nociceptive nerve fibers in the sacroiliac joint in humans.

BACKGROUND AND OBJECTIVES: A positive response to sacroiliac joint intra-articular infiltration with local anesthetics is used to confirm sacroiliac joint pain. However, current anatomical and histological knowledge concerning the anatomy of pain perception within the sacroiliac joint intra- and peri-articular structures is insufficient to explain the efficacy of this infiltration, because of the use of unspecific histochemical visualization techniques. METHODS: In this study, immunohistochemistry for calcitonin gene-related peptide (CGRP) and substance P was used to trace nociceptive fibers and receptors in the anterior and interosseous sacroiliac ligaments obtained from 5 human cadavers without history of sacroiliac joint pain. RESULTS: Microscopic analysis of stained slides showed presence of CGRP and substance P immunoreactive fibers. Thick, wavy, formed bundles were observed in dense and loose connective tissue, whereas single, beaded nerve fibers, occasionally ramified, were observed more frequently in the dense connective tissue and next to blood vessels. Based on their morphologic features, these immunoreactive structures were classified as receptors type IV. Additionally, receptors type II were found in anterior and interosseous ligaments, which contained CGRP or substance P immunoreactive free nerve endings. CONCLUSIONS: We conclude that the presence of CGRP and substance P immunoreactive fibers in the normal anterior capsular ligament and interosseous ligament provides a morphological and physiological base for pain signals originating from these ligaments. Therefore, diagnostic infiltration techniques for sacroiliac joint pain should consider extra- as well as intra-articular approaches.

Neuroinflammation in Parkinson's patients and MPTP-treated mice is not restricted to the nigrostriatal system: microgliosis and differential expression of interleukin-1 receptors in the olfactory bulb.

Neuroinflammation may play a role in the pathogenesis of Parkinson's disease (PD). The present study questioned whether this neuroinflammatory response differs between the olfactory bulb, as an early affected region and the nigrostriatal system. Indeed, increased microgliosis was shown in post-mortem olfactory bulb of PD patients. Also in olfactory bulb of MPTP-treated mice, microgliosis and increased expression of IL-1alpha, IL-1beta and IL-1ra mRNA was observed early after treatment. These observations implicate that neuroinflammation is not restricted to the nigrostriatal system. MPTP-induced microgliosis in striatum and olfactory bulb was reduced in IL-1alpha/beta knockout mice, indicating that IL-1 affects microglia activation. Importantly, MPTP induced differential regulation of IL-1 receptors. mRNA levels of IL-1RI and, to a lesser extent, IL-1RII were increased in striatum. Interestingly, in the olfactory bulb only IL-1RII mRNA was enhanced. We suggest that differential regulation of IL-1 signaling can serve as an important mechanism to modulate neuroinflammatory activity after MPTP treatment and possibly during PD.

A 100% increase of dopaminergic cells in the olfactory bulb may explain hyposmia in Parkinson's disease.

Hyposmia is one of the most prevalent symptoms of Parkinson's disease. It may occur even before the motor symptoms start. To determine whether the olfactory dysfunctions, like the motor symptoms, are associated with a loss of dopamine, the number of dopaminergic cells in the olfactory bulb of Parkinson's disease patients was studied using tyrosine hydroxylase immunohistochemistry. The quantitative analysis reveals that the total number of tyrosine hydroxylase-immunoreactive neurons in the olfactory bulb is twice as high in Parkinson patients compared to age and gender-matched controls. Because dopamine is known to inhibit olfactory transmission in the olfactory glomeruli, we suggest that the increase of dopaminergic neurons in the olfactory bulb is responsible for the hyposmia in Parkinson patients. The increase of dopamine in the olfactory bulb explains why olfaction does not improve with levodopa therapy.

Anatomical and pathological considerations in percutaneous vertebroplasty and kyphoplasty: a reappraisal of the vertebral venous system.

OBJECTIVES: To focus attention of the clinician on the anatomy and (patho)physiology of the vertebral venous system, so as to offer a tool to better understand and anticipate (potential) complications that are related to the application of percutaneous vertebroplasty and kyphoplasty. BACKGROUND: Percutaneous vertebroplasty and kyphoplasty are newly developed, minimally invasive techniques for the relief of pain and for the strengthening of bone in vertebral body lesions. With the clinical implementation of these techniques, a number of serious neurologic and cardiopulmonary complications have been reported in the international medical literature. Most complications appear to be related to the extrusion of bone cement into the vertebral venous system. METHODS: The literature about complications of percutaneous vertebroplasty and kyphoplasty is reviewed, and the anatomic and (patho)physiologic characteristics of the vertebral venous system are reported. Based on what is currently known from the anatomy and physiology of the vertebral venous system, the procedures of percutaneous vertebroplasty and kyphoplasty are analyzed, and suggestions are made to improve the safety of these techniques. CONCLUSIONS: Thorough knowledge of the anatomic and (patho)physiologic characteristics of the vertebral venous system is mandatory for all physicians that participate in percutaneous vertebroplasty and kyphoplasty. To reduce the risk of cement extrusion into the vertebral venous system during injection, vertebral venous pressure should be increased during surgery. This can be achieved by operating the patient in the prone position and by raising intrathoracic venous pressure with the aid of the anesthesiologist during intravertebral instrumentation and cement injection. Intensive theoretical and practical training, critical patient selection, and careful monitoring of the procedures, also taking into account patient positioning and intrathoracic and intra-abdominal pressures, will help to facilitate low morbidity outcomes in these very promising minimally invasive techniques.