The nocardiae are bacteria belonging to the aerobic actinomycetes. They are an important part of the normal soil microflora worldwide. The type species, Nocardia asteroides, and N. brasiliensis, N. farcinica, N. otitidiscaviarum, N. nova, and N. transvalensis cause a variety of diseases in both normal and immunocompromised humans and animals. The mechanisms of pathogenesis are complex, not fully understood, and include the capacity to evade or neutralize the myriad microbicidal activities of the host. The relative virulence of N. asteroides correlates with the ability to inhibit phagosome-lysosome fusion in phagocytes; to neutralize phagosomal acidification; to detoxify the microbicidal products of oxidative metabolism; to modify phagocyte function; to grow within phagocytic cells; and to attach to, penetrate, and grow within host cells. Both activated macrophages and immunologically specific T lymphocytes constitute the major mechanisms for host resistance to nocardial infection, whereas B lymphocytes and humoral immunity do not appear to be as important in protecting the host. Thus, the nocardiae are facultative intracellular pathogens that can persist within the host, probably in a cryptic form (L-form), for life. Silent invasion of brain cells by some Nocardia strains can induce neurodegeneration in experimental animals; however, the role of nocardiae in neurodegenerative diseases in humans needs to be investigated.

Nocardia species: host-parasite relationships.

The incidence of subarachnoid haemorrhage (SAH) is 6-8 per 100 000 person years, peaking in the sixth decade. SAH, mostly due to rupture of an intracranial aneurysm, accounts for a quarter of cerebrovascular deaths. Aneurysms increase in frequency with age beyond the third decade, are 1.6 times more common in women and are associated with a number of genetic conditions. Prospective autopsy and angiographic studies indicate that between 3.6 and 6% of the population harbour an intracranial aneurysm. Studies have found an increased rate of SAH in first degree relatives of SAH patients (relative risk 3.7-6.6). In affected families, the most frequent relationship between sufferers is sibling to sibling. The rupture rate of asymptomatic aneurysms was thought to be 1-2% per annum, but the recent International Study of Unruptured Intracranial Aneurysms found that the rupture rate of small aneurysms was only 0.05% per annum in patients with no prior SAH, and 0.5% per annum for large (>10 mm diameter) aneurysms and for all aneurysms in patients with previous SAH. Non-invasive tests such as magnetic resonance angiography (MRA), computed tomographic angiography (CTA) and transcranial Doppler (TCD) have been advocated as alternatives to intra-arterial digital subtraction angiography to screen for aneurysms. Although all are promising techniques, the quality of data testing their accuracy is limited. Overall reported sensitivity for CTA and MRA (TCD is poorer) was 76-98% and specificity was 85-100%, but many subjects had an aneurysm or recent SAH, which could overestimate accuracy. CTA and MRA are much poorer methods for the detection of aneurysms <5 mm diameter, which account for up to one-third of unruptured aneurysms. Elective surgical clipping of asymptomatic aneurysms has a morbidity of 10.9% and mortality of 3. 8%. Treatment of aneurysms by Guglielmi coils, for which there is less long-term follow-up available, has a 4% morbidity and 1% mortality, but only achieves complete aneurysm occlusion in 52-78% of cases. There has been interest in screening for aneurysms, but the indication for, and cost effectiveness of screening are unclear because aneurysm prevalence varies, rupture rate is low, non-invasive imaging tests are not yet accurate enough to exclude small aneurysms and the morbidity and mortality for elective surgical treatment of unruptured aneurysms is high. There may be a limited role for investigation of high risk subgroups. Ideally, screening in such subgroups should be tested in a randomized trial. The avoidance of risk factors for aneurysms such as smoking, hypertension and hypercholesterolaemia should be part of the management of at-risk subjects.

The detection and management of unruptured intracranial aneurysms

The concept of contrast imaging was introduced to ultrasound almost 30 years ago. The development of ultrasound contrast agents (USCAs), initially slowed by technical limitations, has become more dynamic during the past decade. The ideal USCA should be non-toxic, injectable intravenously, capable of crossing the pulmonary capillary bed after a peripheral injection, and stable enough to achieve enhancement for the duration of the examination. While satisfying cost–benefit requirements, it should provide not only Doppler but also gray-scale enhancement. Already, Doppler examinations are improved by using USCAs when studying deep and small vessels, vessels with low or slow flow, or vessels with a non-optimal insonation angle. Ultrasound contrast agents also enhance detection of flow within abnormal vessels, including tumor vascularization and stenotic vessels, and provide better delineation of ischemic areas. Research is focusing on the development of specific contrast imaging sequences that allow detection of tissue enhancement similar to that obtained with CT or MRI. These sequences take advantage of the non-linear behavior of the microbubbles within the ultrasound field, bringing real-time perfusion imaging for liver, kidney, and the myocardium into reach. New objectives include targeted agents that could further widen USCA applications to specific delivery of active drugs such as anticoagulants or cytotoxic compounds. The combination of new generations of USCAs and new ultrasound image sequences appears to be very promising and currently represents a significant part of ultrasound research.

Ultrasound contrast agents: properties, principles of action, tolerance, and artifacts.

Summary Over the past 15 years the use of transcranial B-mode sonography to assess brainstem and subcortical brain structures has become an important tool for the diagnosis and differential diagnosis of various movement disorders. The most widely recognised finding for movement disorders has been an increase in echogenicity of the substantia nigra, an area of the midbrain that is affected in idiopathic Parkinson's disease (PD). This finding has enabled the reliable diagnosis of PD with high predictive values. Other sonographic features, such as hypoechogenicity of the brainstem midline and hyperechogenicity of the lentiform nucleus, might help the differential diagnosis of PD and other movement disorders. This Review provides detailed information about the advantages and limitations of this novel neuroimaging method, including guidelines for the scanning procedure and considerations on the origin of ultrasound abnormalities. We discuss the use of transcranial sonography for early and preclinical diagnosis and for differential diagnosis of PD and other movement disorders, and we compare this method with other functional neuroimaging strategies. Transcranial B-mode sonography is a reliable, non-invasive, commonly available, easily applicable, and inexpensive method, which provides new information about the morphology of the brain to help the diagnosis of various movement disorders. Thus, this neuroimaging method could be recommended for general application in the diagnosis and differential diagnosis of PD.

https://www.thelancet.com/pdfs/journals/laneur/PIIS1474-4422(08)70239-4.pdf

Transcranial sonography in movement disorders

OBJECTIVE: Intraoperative magnetic resonance imaging (MRI) is now available with the General Electric MRI system for dedicated intraoperative use. Alternatively, non-dedicated MRI systems require fewer specific adaptations of instrumentation and surgical techniques. In this report, clinical experiences with such a system are presented. METHODS: All patients were surgically treated in a twin operating theater, consisting of a conventional operating theater with complete neuronavigation equipment (StealthStation and MKM), which allowed surgery with magnetically incompatible instruments, conventional instrumentation and operating microscope, and a radiofrequency-shielded operating room designed for use with an intraoperative MRI scanner (Magnetom Open; Siemens AG, Erlangen, Germany). The Magnetom Open is a 0.2-T MRI scanner with a resistive magnet and specific adaptations that are necessary to integrate the scanner into the surgical environment. The operating theaters lie close together, and patients can be intraoperatively transported from one room to the other. This retrospective analysis includes 55 patients with cerebral lesions, all of whom were surgically treated between March 1996 and September 1997. RESULTS: Thirty-one patients with supratentorial tumors were surgically treated (with navigational guidance) in the conventional operating room, with intraoperative MRI for resection control. For 5 of these 31 patients, intraoperative resection control revealed significant tumor remnants, which led to further tumor resection guided by the information provided by intraoperative MRI. Intraoperative MRI resection control was performed in 18 transsphenoidal operations. In cases with suspected tumor remnants, the surgeon reexplored the sellar region; additional tumor tissue was removed in three of five cases. Follow-up scans were obtained for all patients 1 week and 2 to 3 months after surgery. For 14 of the 18 patients, the images obtained intraoperatively were comparable to those obtained after 2 to 3 months. Intraoperative MRI was also used for six patients undergoing temporal lobe resections for treatment of pharmacoresistant seizures. For these patients, the extent of neocortical and mesial resection was tailored to fit the preoperative findings of morphological and electrophysiological alterations, as well as intraoperative electrocorticographic findings. CONCLUSION: Intraoperative MRI with the Magnetom Open provides considerable additional information to optimize resection during surgical treatment of supratentorial tumors, pituitary adenomas, and epilepsy. The twin operating theater is a true alternative to a dedicated MRI system. Additional efforts are necessary to improve patient transportation time and instrument guidance within the scanner.

Intraoperative Magnetic Resonance Imaging with the Magnetom Open Scanner: Concepts, Neurosurgical Indications, and Procedures: A Preliminary Report

The aim of this study was to evaluate whether intra-operative ultrasound (= IOUS) is a suitable tool to detect residual tumour tissue after gross total resection in supratentorial gliomas. During a period of 18 months 45 patients with supratentorial gliomas (38 high-grade and 9 low-grade, according to the WHO-grading system [42]) were operated on. A series of 78 biopsies was taken from the resection cavity under continuous sonographic control at the end of surgery. Gross total tumour resection was intended in 34 patients (= 76%). The biopsy specimens were matched with the sonographic features at each biopsy site. The sonographic appearance of the resection margins were classified into 2 groups: (1) Irregular hyperechoic areas extending from the cavity into the iso-echogenic brain tissue and (2) a dense small (< or = 3 mm in diameter) rather regular hyperechoic rim surrounding the resection cavity. 47 out of 53 biopsies taken from hyperechoic areas (group I) (36 high-grade/11 low-grade) revealed solid tumour tissue (= 89%). 34 (= 72%) of these 47 areas were microscopically assessed as inconspicuous by the surgeon. 6 samples (4 high-grade/2 low-grade) contained tumour infiltration zone. 25 biopsies (23 high-grade/2 low-grade) taken from the hyperechoic rim [group 2] were diagnosed as follows: Normal brain tissue in 11, tumour infiltration zone in 8 and solid tumour tissue in 6 cases. Of 34 cases with "gross total removal" according to the surgeon's assessment 25 showed sonographic signs of residual tumour tissue, which was confirmed histologically as solid tumour tissue in 22 of these cases. It is concluded, that IOUS following resection of supratentorial gliomas can detect residual tumour tissue with high specificity and thus improve gross total resection. However, a thin hyperechoic rim surrounding the resection cavity (less than 3 mm in diameter) is a non-specific finding, which can mask thin residual tumour layers and therefore needs further evaluation of its nature.

Correlation of intra-operative ultrasound with histopathologic findings after tumour resection in supratentorial gliomas. A method to improve gross total tumour resection.

Transcranial color-coded real-time sonography (TCCS) was performed in 57 patients with primary intracranial brain tumors (n = 49) or arteriovenous malformations (n = 8) to evaluate its diagnostic potential. In 46 patients (81%), lesions could be identified employing this technique. In 7 patients, transcranial ultrasound examination was not feasible because of bone thickness; in the remaining 4 patients, the tumor was indistinguishable from adjacent brain tissue despite sufficient insonation, suggesting that these neoplasms are isoechogenic. The sonographic features of brain tumors were very similar: a hyperechogenic matrix of the lesion was interspersed by hypoechogenic pixels. Larger hypoechogenic areas (0.5-1 cm) gave evidence of tumor necrosis. Differences between the findings of TCCS and computed tomography concerning tumor size were found in 7 patients, in whom TCCS revealed an area of smaller extension within the corresponding hypodense area on the computed tomographic scan. Perifocal brain edema could not be detected by ultrasound examination. In 13 patients, a thin, hypoechogenic peritumoral halo was disclosed that did not correlate with perifocal brain edema identified by computed tomography and that may have been due to compression of adjacent parenchyma. In patients with arteriovenous malformations, TCCS permitted the identification of the main feeders, the nidus, and the draining venous system by color-coded depiction of intravascular blood flow. In conclusion, TCCS is an additional method for initial diagnosis and highly suitable for follow-up in tumor patients and provides valuable information about tissue characteristics and blood flow.

Transcranial color-coded real-time sonography in the evaluation of intracranial neoplasms and arteriovenous malformations.

PURPOSE: To study the potential of contrast material-enhanced transcranial color-coded real-time sonography (TCCS) in detection of primary intracranial tumor vascularization. MATERIALS AND METHODS: Primary central nervous system (CNS) tumors in 28 patients were examined with TCCS before and during administration of a transpulmonary, stable, galactose, microparticle-based ultrasound (US) contrast agent. All patients underwent cranial computed tomography and magnetic resonance imaging; nine patients also underwent intraarterial digital subtraction angiography. RESULTS: All lesions were hyperechoic on B-mode US scans except one grade 2 astrocytoma. The location and extent of hyperechoic lesions correlated well with findings on CT scans and MR images. After injection of contrast material, color Doppler flow signals were seen in nine of 14 low-grade lesions and 14 of 14 high-grade lesions. High-grade malignant tumors always had atypical arterial and venous Doppler spectra with irregular distribution of Doppler...

Vascularization of primary central nervous system tumors: detection with contrast-enhanced transcranial color-coded real-time sonography.

Transcranial colour-coded real-time sonography (TCCS) was carried out in 25 patients with brain tumours to determine whether this noninvasive method provides additional information about the extent of solid tumour, its differentiation from oedema, and its tissue components. All 25 patients had serial computed tomography (CT)-guided stereotactic biopsies. Comparison of ultrasound, CT and histological findings revealed that the vast majority of contrast enhancing areas on CT were hyperechogenic (32/33; 97%) and contained tumour tissue (29/32; 91%). Hyperechogenic areas always represented solid tumour (23/23 patients), even when CT showed low density non-enhancing lesions. In lestons hypoechogenic on TCCS and low density on CT, histology consistently revealed necrotic tumour (7/7). Biopsies obtained from parenchyma with normal echogenicity revealed tumour in only 3 of 16 speciemens. Despite the high specificity of TCCS in the differentiation of tumour components, its sensitivity to tumour was inferior to that of CT (24/25; 96%). TCCS thus allows noninvasive preoperative identification of tumour tissue and its extent setting.

Reliability of transcranial colour-coded real-time sonography in assessment of brain tumours: correlation of ultrasound, computed tomography and biopsy findings

The aim of this study was to evaluate guidance techniques and patient outcomes of ultrasound-guided neuronavigation of deep-seated intracerebral cavernous hemangiomas (CAs). Thirty-five patients with deep-seated intracerebral CAs with sizes ranging between 7 and 45 mm were operated upon only with ultrasound-guidance. Twenty-seven were located in or near eloquent regions. In 30 patients dissection to the lesion was performed through sulci and fissures. The best approach to a lesion based on surface anatomy and depth was determined using sonographic information. Navigation was done sonographically. In five patients the shortest approach via a corticotomy was determined sonographically. Twenty-six patients had no neurological deficit postoperatively. Preoperative deficits improved in seven of nine patients. Fifteen of 19 patients suffering epileptic seizures had no seizures postoperatively. Intraoperative sonography revealed residual CA tissue after microsurgical extirpation in two cases. This report shows that intraoperative sonographic navigation provides safe guidance to deep-seated CAs with good clinical outcome independent of size.

A. Krone

Papers

Correlation of intra-operative ultrasound with histopathologic findings after tumour resection in supratentorial gliomas. A method to improve gross total tumour resection.

Transcranial color-coded real-time sonography in the evaluation of intracranial neoplasms and arteriovenous malformations.

Vascularization of primary central nervous system tumors: detection with contrast-enhanced transcranial color-coded real-time sonography.

Reliability of transcranial colour-coded real-time sonography in assessment of brain tumours: correlation of ultrasound, computed tomography and biopsy findings

Ultrasound-guided neuronavigation of deep-seated cavernous haemangiomas: clinical results and navigation techniques.