Haring J. W. Nauta

Afferents to the rat caudoputamen studied with horseradish peroxidase. An evaluation of a retrograde neuroanatomical research method

The potential for using the physiologically occurring retrograde axonal transport of protein as a neuroanatomical tool for identifying the origin of neuronal connections within the adult central nervous system has been evaluated for the case of the rat caudoputamen. Following injections of a marker protein, in this case horseradish peroxidase (HRP), centering on but not limited solely to the caudoputamen, peroxidase labeled cell bodies could be identified in several cell territories known or thought to contain afferents to this structure. These included the pars compacta of the substantia nigra, the intralaminar and parafascicular nuclei of the thalamus, and the dorsal nucleus of the midbrain raphe. In cases where only the caudoputamen and external segment of the globus pallidus were labeled directly at the injection site, no peroxidase- containing cells could be identified in the neocortex or in the thalamus outside the intralaminar and parafascicular nuclei. The evidence presented suggests first, that the degree of localization at the injection site is compatible with approaching some problems in neuroanatomy; second, that anterograde transport of the marker protein, if it occurs, does not appear to confound the interpretation of retrogradely labeled cell bodies; third, that many, though not all, afferent cell populations can be identified; and fourth, that labeling by axons in passage does not appear to be a problem. A detailed description of the method, abilities and limitations of the technique, and sources of misinterpretation are also provided.

Electron microscopic observations of horseradish peroxidase transported from the caudoputamen to the substantia nigra in the rat: possible involvement of the agranular reticulum.

The intracellular distribution of horeseradish peroxidase (HRP) transported intraaxonally from the caudoputaminal complex to the substantia nigra has been examined with the electron microscope. The reciprocal axonal connections between the caudoputamen and the substantia nigra permitted observation not only of HRP transported retrogradely from axons and axon terminals in the caudoputamen to the cell bodies of origin in the pars compacta of the substantia nigra, but also provided information suggesting that HRP may be transported anterogradely by neurons of the caudoputamen to their terminals, which are especially numerous in the pars reticulata of the substantia nigra. Special attention was focused on observations which might elucidate the manner in which exogenous proteins are compartmentalized and transported intracellularly. It is suggested that the agranular reitculum is involved in the retrograde transport of proteins which are pinocytosed near the axon terminal and ultimately reach lysosomes in the perikaryon. A possible anterograde movement of HRP may also involve the agranular reticulum. The implications such findings have on the use of HRP in neuroanatomical tracing techniques are also discussed.

Xanthochromic cysts associated with meningioma.

Three cases of cystic meningioma encountered in one year are presented. It appears from a review of the literature, and an analysis of these three cases, that large xanthochromic cerebral cysts may be associated with meningiomas in any of three configurations: (1) centrally within the tumour; (2) peripherally within the tumour; (3) in the adjacent brain. Regardless of which configuration applies, the CAT scan appearance of such cystic meningiomas may mimic that of a glial tumour with cystic or necrotic change, and lead to an incorrect presumptive diagnosis. This false impression may be perpetuated by the gross appearance at operation, which can also mimic malignant glioma. Although several radiological features should suggest the possible presence of a cystic meningioma, we know of no definite radiological means of differentiating this lesion from the more common malignant glioma. This finding should underline the need to biopsy all suspected cerebral neoplasms, regardless of how much their appearance on CAT scan may suggest malignant glioma.

Cerebral pressure autoregulation in traumatic brain injury.

An understanding of normal cerebral autoregulation and its response to pathological derangements is helpful in the diagnosis, monitoring, management, and prognosis of severe traumatic brain injury (TBI). Pressure autoregulation is the most common approach in testing the effects of mean arterial blood pressure on cerebral blood flow. A gold standard for measuring cerebral pressure autoregulation is not available, and the literature shows considerable disparity in methods. This fact is not surprising given that cerebral autoregulation is more a concept than a physically measurable entity. Alterations in cerebral autoregulation can vary from patient to patient and over time and are critical during the first 4-5 days after injury. An assessment of cerebral autoregulation as part of bedside neuromonitoring in the neurointensive care unit can allow the individualized treatment of secondary injury in a patient with severe TBI. The assessment of cerebral autoregulation is best achieved with dynamic autoregulation methods. Hyperventilation, hyperoxia, nitric oxide and its derivates, and erythropoietin are some of the therapies that can be helpful in managing cerebral autoregulation. In this review the authors summarize the most important points related to cerebral pressure autoregulation in TBI as applied in clinical practice, based on the literature as well as their own experience.

Parkinson's disease subtypes: clinical classification and ventricular cerebrospinal fluid analysis

The current study presents preliminary data regarding the development and validation of a rating system designed to classify PD patients into clinical subgroups. Using portions of the Unified Parkinsons Disease Rating Scale, a ratio value was derived, yielding three patient subtypes: a tremor-dominant group (T), an akinetic-rigid group (AR), and a mixed group (MX). Validation of the schema was conducted by grouping PD surgical candidates into specific disease subtypes and evaluating differences in neurotransmitter profiles among disease subtypes and non-PD neurological controls. High pressure liquid chromatography analysis of ventricular cerebrospinal fluid indicated 5-hydroxyindoleacetic acid was significantly lower in the AR and MX groups compared to non-PD controls; whereas, glycine was significantly higher in the AR group compared to the T, MX, and control groups. The results suggest that an operational approach can be utilized to differentiate between PD subtypes with distinct neurochemical profiles.

Brain stem abscess managed with computed tomography-guided stereotactic aspiration.

The importance of stereotactic aspiration to the successful management of three cases of brain stem abscess is discussed with special reference to the advantages offered over medical treatment alone. Stereotactic aspiration allows evacuation of pus, accurate bacteriological diagnosis, selection of an optimal antibiotic regimen, and instillation of antibiotics directly into the abscess cavity. In two of the three cases described here, the abscess reaccumulated after initial aspiration despite appropriate maximal medical therapy. A repeat aspiration was required before resolution occurred. We conclude that medical management alone is not adequate for some cases of brain stem abscess. There was no morbidity that could be attributed to the procedure, suggesting that the risk of stereotactic aspiration is probably quite low and is likely to be less than the risk of incorrect diagnosis, suboptimal choice of antibiotics, or progression of the lesion despite appropriate maximal medical therapy.

An Animal Model for Neuron-Specific Spinal Cord Lesions by the Microinjection of N-Methylaspartate, Kainic Acid, and Quisqualic Acid

It has been shown that N-methylaspartate (NMA), kainic acid (KA), and quisqualic acid (QA) can produce preferential neuronal damage in various parts of the striatum, hippocampus, and thalamus with relative sparing of axons in transit. Thus far, the evidence that axons in transit escape destruction has been based largely on histological observations. To test the functional integrity of axons in passage, we made unilateral lesions with these agents in the cervical spinal cord of rats and compared the subsequent functional deficits with those seen after spinal cord hemisections. Observations were made in 14 rats. In each case, a laminectomy at the C6-C7 level was performed under general anesthesia. Animals receiving microinjections of KA, QA, or NMA showed motor and sensory deficits only in the ipsilateral forepaw and remained able to use the hindpaws normally. By contrast, animals undergoing spinal cord hemisection developed obvious motor deficits in the ipsilateral hindpaw in addition to the deficits in the forepaw. Histological observations of the spinal cords confirmed an extensive gray matter destruction with relative preservation of the long tracts in animals injected with KA, QA, and NMA. In addition, it was noted that spinal cord neurons appear relatively less sensitive to KA and more sensitive to QA than neurons in the thalamus, striatum, or hippocampus. The possible application of these findings for the production of dorsal root entry zone lesions will be discussed.

Blastomycosis of the lumbar spine: case report and review of the literature, with emphasis on diagnostic laboratory tools and management

Abstract We report on the conservative and surgical management of a patient with blastomycosis of the lumbar spine, causing severe and crippling deformity. The diagnosis was made through biopsy. Curative removal, reconstruction and realignment of the spine were achieved. Imaging modalities were highlighted, with a detailed discussion of the histology and conservative and surgical management. We emphasize the importance of early, aggressive treatment of blastomycosis to prevent deformity and disability, and to enable identification of the best management of a destructive lesion with deformity. This case demonstrates that empirical treatment should not be used in cases of unusual sinus and abscess locations. Specific diagnosis and early treatment are indicated to prevent dreadful complications and spinal deformity resulting from blastomycosis. Aggressive antifungal therapy can cure the disease but does not control complications related to deformity. The latter can only be addressed by surgical reconstruction. We review the literature of surgical treatment, focusing on abscess drainage, bone fusion and posterior instrumentation in the absence of addressing the deformity component.

Percutaneous Transpedicular Management of Discitis

PURPOSE To present the technique of percutaneous transpedicular biopsy and debridement of discs in diagnosis and management of discitis. MATERIALS AND METHODS Fifteen patients underwent disc biopsy through a transpedicular approach with local anesthesia and fluoroscopic guidance. An attempt was made to debride the disc as much as possible. A surgical vacuum drain was deployed through the transpedicular tract when there was persistent drainage. RESULTS Fifteen patients underwent percutaneous transpedicular disc biopsy and debridement of disc for suspected discitis. Three patients underwent biopsy only and 12 underwent percutaneous discectomy. Six patients had at least one positive culture. Eight patients who underwent discectomy had immediate improvement of pain or neurologic symptoms, obviating emergency surgical debridement of the disc. Four patients did not improve and underwent surgical debridement and fusion. CONCLUSIONS Transpedicular biopsy of the disc is an effective technique for adequate tissue retrieval and diagnosis of discitis. Adequate debridement in selected patients with antibiotic therapy may be definitive. Epidural extension of discitis and massive vertebral destruction precludes percutaneous treatment.

The role of c-AMP-dependent protein kinase in spinal cord and post synaptic dorsal column neurons in a rat model of visceral pain.

Visceral noxious stimulation induces central neuronal plasticity changes and suggests that the c-AMP-dependent protein kinase (PKA) signal transduction cascade contributes to long-term changes in nociceptive processing at the spinal cord level. Our previous studies reported the clinical neurosurgical interruption of post synaptic dorsal column neuron (PSDC) pathway by performing midline myelotomy effectively alleviating the intractable visceral pain in patients with severe pain. However, the intracellular cascade in PSDC neurons mediated by PKA nociceptive neurotransmission was not known. In this study, by using multiple experimental approaches, we investigated the role of PKA in nociceptive signaling in the spinal cord and PSDC neurons in a visceral pain model in rats with the intracolonic injection of mustard oil. We found that mustard oil injection elicited visceral pain that significantly changed exploratory behavior activity in rats in terms of decreased numbers of entries, traveled distance, active and rearing time, rearing activity and increased resting time when compared to that of rats receiving mineral oil injection. However, the intrathecal infusion of PKA inhibitor, H89 partially reversed the visceral pain-induced effects. Results from Western blot studies showed that mustard oil injection significantly induced the expression of PKA protein in the lumbosacral spinal cord. Immunofluorescent staining in pre-labeled PSDC neurons showed that mustard oil injection greatly induces the neuronal profile numbers. We also found that the intrathecal infusion of a PKA inhibitor, H89 significantly blocked the visceral pain-induced phosphorylation of c-AMP-responsive element binding (CREB) protein in spinal cord in rats. The results of our study suggest that the PKA signal transduction cascade may contribute to visceral nociceptive changes in spinal PSDC pathways.