Brain biopsies

According to chnico-pathological studies, the diagnosis of probable AD can be made with an accuracy of about 85% while the diagnosis of definite AD stiU relies on post mortem neu-ropathological proof, apart from the rare case where a brain biopsy can be performed. A more sensitive and accurate diagnostic method, which should also be non-invasive, would be highly desirable [2]. 

In experiments done many years ago on epileptic patients who were undergoing brain surgery, small brain biopsies were taken at operation. The concentration of anti-convulsant drug was measured in both the brain tissue and in the plasma from simultaneously-withdrawn venous blood. For the drugs phenobarbitone and phenytoin, a linear correlation was observed between plasma and brain concentrations. This suggested that plasma concentrations of anti-convulsants could reflect brain concentrations, and therefore, presumably concentrations at the receptor sites within the brain substance. 

Primary cultures of cerebromicrovascular endothelial cells (CEC) derived from rat, bovine, porcine, mouse and human can rapidly lose key phenotypic markers of the blood-brain barrier (BBB) and undergo cellular senescence after a limited number of divisions in vitro. Furthermore, expression of BBB markers varies considerably among BCEC obtained from different species. These issues, compounded with the problems associated with very limited availability of human brain biopsies, small initial yield of cells and short proliferative life span of human cells, greatly restrict the utility of primary human BCEC as a reliable in vitro BBB model. Therefore, Muruganandam et al. (1997) developed an immortalized human cerebromicrovascular endothelial cell line as an in vitro model of the human blood-brain barrier. 

Pirotte B, Goldman S, Massager N, David P, Wilder D, Vandesteene A, Salmon I, Brotchi J, Levivier M (2004) Comparison of 18F-FDG and llC-methionine for PET-guided stereotactic brain biopsy of gliomas. J Nucl Med 45 1293-1298. 

What are the brain structures or processes where variability accounts for variation in IQ If genetic contributions to inter-individual variation in IQ are in the order of 50% (Devlin et al 1997), which genes are important and what do they control Despite our expanding ability to non-invasively analyse the human brain we cannot count neurons or measure individual myelin sheath thickness. To do this requires studies of clinical populations coming to brain biopsy or autopsy. Work on these populations is slow, expensive, and subject to criticisms of the patient populations or variability due to uncontrollable post-mortem delay effects (Witelson McCulloch 1991). Animals do not have these difficulties. Further, unlike correlative inferential human studies, animal studies can attempt to be causal by actually manipulating the variables of interest. 

CurtiusHC,WolfensbergerM, Steinmann B, Redweik U, Siegfried J. 1974. Mass fragmentography of dopamine and 6-hydroxydopamine. Application to the determination of dopamine in human brain biopsies from the caudate nucleus. J. Chromatogr. 99 529 40... 

The two largest studies have compared HSV PCR on CSF specimens with a brain biopsy in patients with suspected HSV encephalitis. The sensitivity and specificity of PCR were greater than 95%, and the sensitivity of HSV PCR did not decrease significantly until 5 to 7 days after start of therapy. PCR is positive early in the course of illness, usually within the first 24 hours of symptoms, and in some individuals HSV DNA can persist in the CSF for weeks after initiatmg therapy. ... 

Lakeman F, Whitley RJ. Diagnosis of herpes simplex encephalitis Application of polyermase chain reaction to cerebrospinal fluid firom brain-biopsied patients and correlation with disease. National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. J Infect Dis 1995 171 857. 

The initial treatment of CNS toxoplasmosis is usually empirical. Brain biopsy in patients with AIDS may be complicated by... 

Brain biopsies for non-neoplastic diseases often require IHC combined with additional studies such as microbio-logic culture, polymerase chain reaction (PCR), Western blot, or electron microscopy (EM). Specialized centers are available to assist interpretations of these. ... 

Every brain biopsy specimen should be handled in such a way that if inflammation is found at surgery, it will be possible to culture the tissue for bacteria, mycobacteria, and fungi and to use special stains, immunostain-ing techniques, and electron microscopy. This author s experience has been that for organisms that grow in vitro, microbiologic culture is preferable to histochemi-cal stains, IHC, or polymerase chain reaction (PCR) assay if sampling of the lesion is uniform. Prior antibiotic treatment or non-uniform sampling of focal infection affects individual cases. 

Cowdry type A bodies of HSV are not easy to demonstrate in small brain-biopsy specimens. This argues for sensitive and specific methods of identification such as in situ hybridization (ISH), PCR, and IHC. s Electron microscopy may demonstrate viral particles within the nuclei or cytoplasm but is less sensitive and less specific. Culture and sequential serologic CSF evaluations are slow but are still the most accurate methods of diagnosis for many viral CNS infections, including HSV. 

Brain biopsy may show a destructive process within the white matter, with multiple lipid-laden macrophages. 

FIGURE 20.60 Primary demyelination with preservation of brown NF-positive axons. Some axons are swollen and are called spheroids. Lipid-laden macrophages and gliosis are not stained brown in this section of this brain biopsy specimen, but their pale gray features are still evident. 

Eirlik KS, Martinez AJ, Lunsford LD. Use of cytological preparations for the intraoperative diagnosis of stereotactically obtained brain biopsies A 19-year experience and survey of neuropathologists. J Neurosurg. 1999 91 454-458. 

Zimmer C, Daeschlein G, Patt S, et al. Strategy for diagnosis of Toxoplasma gondii in stereotactic brain biopsies. Stereotact Funct Neurosurg. 1991 56 66-75. 

Prayson RA, Estes ML. Stereotactic brain biopsy for diagnosis of progressive multifocal leukoencephalopathy. South Med J. 1993 86 1381-1394. 

Hornef, M. W., Iten, A., Maeder, P., Villemure, J. G., and Regli, L. (1999). Brain biopsy in patients with acquired immunodeficiency syndrome. Arch. Intern. Med. 159, 2590-2596. 

To determine whether the local tissue water content exerts an influence on the blood flow rate, the rCBF values were plotted against the local tissue water content found in the corresponding brain biopsies. For comparison, the mean of the individual values of the water content of cortex and subjacent white matter were used. A linear regression, with... 

The majority of patients infected with the human immunodeficiency virus (HIV) have abnormalities in the central nervous system. It is frequently possible to provide a specific diagnosis on the basis of abnormalities seen by MR imaging the diagnosis is difficult in the presence of focal abnormalities with mass effect, as for example the differentiation between toxoplasmosis and cerebral lymphomas. Some clinicians recommend that all patients with AIDS and brain masses should first receive antibiotics for toxoplasmosis [83]. If improvement does not occur after medication, biopsy is considered. The most accurate diagnosis could be achieved by brain biopsy, but this can lead to substantial morbidity and mortality. Any technique that allows earlier diagnosis would enable earlier commencement of appropriate therapy. This is of particular importance in the case of lymphoma because untreated mean survival is short whereas radiation therapy and steroids may improve survival. H MRS showed significantly different biochemical profiles for AIDS-related brain lesions in 26 patients, which helped in correct diagnosis [83]. HIVpositive patients (109) were found to have focal intracranial lesions [84] 56 of these... 

One of the earliest robotic systems developed for precise CT-guided stereotactic brain biopsy was the neurosurgical robot Minerva (Glauser et al. 1995). A 5-DOF robot with two linear axes (vertical and lateral), two rotary axes (moving in a horizontal and vertical plane), and a linear axis (to move the tool to and from the patient s head) was designed to work within the CT scanner so that the surgeon could follow the position of the instruments on successive... 

Minerva [2] was designed for precision image-guided needle placement in stereotactic brain biopsy. The system has 5 DOFs and was designed to intraoperatively control the direction of the tool in real time under computed tomography guidance. 

Histologic and histochemical properties of material from brain biopsy or rectum biopsy render further evidence for the diagnosis, and secure to some degree the differentiation of TSD from other types of amaurotic family idiocy. Lipid analyses from brain tissue with the demonstration of the increase in Tay-Sachs ganglioside finally provide conclusive evidence for the diagnosis. 

The results of chemical analyses of brain biopsy or autopsy specimens, as reported by different laboratories, are particularly difficult to interpret. Considerable discrepancies in such data with regard to the concentrations of individual lipid fractions may to a significant degree be due to the fact that in the majority of cases analyses were performed during the period of the considerable physiologic change in brain lipid composition which accompanies myelination. 

Truwit, C. L. (1999). Brain biopsy using high-field strength interventional magnetic resonance imaging, Neurosurgery 44, 807-814. 

Tronnier, V., Staubert, A., Wirtz, R., Knauth, M., Bonsanto, M., and Kunze, S. (1999). MRI-guided brain biopsies using a 0.2 Tesla open magnet, Minim. Invasive Neurosurg. 42, 118—122. 

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