[Degenerative intervertebral disc processes : Current aspects of diagnosis]. / Degenerative Bandscheibenprozesse : Aktuelles zur Befundung.

Starting with the smallest functional unit, the spinal segment including the centrally located intervertebral disc, the spine and pelvis including the sacroiliac and hip joints form a functional unit. The discs play an important role in the complex interaction between disc, osseous and ligamentous structures and the adjacent muscles. Disc pathologies are very frequently associated with changes of the adjacent endplates of the vertebral bodies and can be depicted at an early stage using magnetic resonance imaging (MRI). The focus of the diagnostics and assessment of degenerative disc pathologies should be centered on the clinical problem. The basis for this is the use of a uniform terminology between the disciplines involved.

[Autoimmune reactions and paraneoplastic syndromes]. / Autoimmunreaktionen und Paraneoplasien.

CLINICAL ISSUE: Autoimmune disorders of the central nervous system (CNS) are common but are also a heterogeneous group of diseases. The most common form is multiple sclerosis (MS), others are clinically isolated syndrome (CIS), acute demyelinating encephalomyelitis (ADEM) and neuromyelitis optica spectrum disorders (NMOSD). Paraneoplastic syndromes are rare and tumor-associated, they are not induced by direct invasion of tumor tissue but by tumor-associated autoantibodies mostly against specific CNS proteins, e. g. limbic encephalitis and paraneoplastic cerebellar ataxia or degeneration. DIAGNOSTICS, STANDARD RADIOLOGICAL METHODS, PERFORMANCE AND ACHIEVEMENTS: The correct diagnosis of autoimmune and paraneoplastic syndromes can still be challenging. In addition to the patient history, clinical examination and blood as well as cerebrospinal fluid (CSF) tests, magnetic resonance imaging (MRI) is gaining importance in the diagnostics. It is important not only in primary diagnostics but also in follow-up and therapy monitoring, especially in MS with specific therapies to detect therapy complications, such as progressive multifocal leukoencephalopathy as early as possible. In paraneoplastic syndromes MRI can also be an important component in the diagnostics but can also initially be negative and typical signal changes become visible only in follow-up scans. PRACTICAL RECOMMENDATIONS: In paraneoplastic syndromes the correct diagnosis is based on laboratory tests for specific autoantibodies in serum and CSF. TREATMENT: The treatment of autoimmune and paraneoplastic disorders of the CNS ranges from steroids and immunosuppressive agents to plasmapheresis, depending on the specific disorder.

Splenomegaly, elevated alkaline phosphatase and mutations in the SRSF2/ASXL1/RUNX1 gene panel are strong adverse prognostic markers in patients with systemic mastocytosis.

We evaluated the impact of clinical and molecular characteristics on overall survival (OS) in 108 patients with indolent (n=41) and advanced systemic mastocytosis (SM) (advSM, n=67). Organomegaly was measured by magnetic resonance imaging-based volumetry of the liver and spleen. In multivariate analysis of all patients, an increased spleen volume ⩾450 ml (hazard ratio (HR), 5.2; 95% confidence interval (CI), (2.1-13.0); P=0.003) and an elevated alkaline phosphatase (AP; HR 5.0 (1.1-22.2); P=0.02) were associated with adverse OS. The 3-year OS was 100, 77, and 39%, respectively (P<0.0001), for patients with 0 (low risk, n=37), 1 (intermediate risk, n=32) or 2 (high risk, n=39) parameters. For advSM patients with fully available clinical and molecular data (n=60), univariate analysis identified splenomegaly ⩾1200 ml, elevated AP and mutations in the SRSF2/ASXL1/RUNX1 (S/A/R) gene panel as significant prognostic markers. In multivariate analysis, mutations in S/A/R (HR 3.2 (1.1-9.6); P=0.01) and elevated AP (HR 2.6 (1.0-7.1); P=0.03) remained predictive adverse prognostic markers for OS. The 3-year OS was 76 and 38%, respectively (P=0.0003), for patients with 0-1 (intermediate risk, n=28) or 2 (high risk, n=32) parameters. We conclude that splenomegaly, elevated AP and mutations in the S/A/R gene panel are independent of the World Health Organization classification and provide the most relevant prognostic information in SM patients.

Additional mutations in SRSF2, ASXL1 and/or RUNX1 identify a high-risk group of patients with KIT D816V(+) advanced systemic mastocytosis.

Most patients with KIT D816V(+) advanced systemic mastocytosis (SM) are characterized by somatic mutations in additional genes. We sought to clarify the prognostic impact of such mutations. Genotype and clinical characteristics of 70 multi-mutated KIT D816V(+) advanced SM patients were included in univariate and multivariate analyses. The most frequently identified mutated genes were TET2 (n=33 of 70 patients), SRSF2 (n=30), ASXL1 (n=20), RUNX1 (n=16) and JAK2 (n=11). In univariate analysis, overall survival (OS) was adversely influenced by mutations in SRSF2 (P<0.0001), ASXL1 (P=0.002) and RUNX1 (P=0.03), but was not influenced by mutations in TET2 or JAK2. In multivariate analysis, SRSF2 and ASXL1 remained the most predictive adverse indicators concerning OS. Furthermore, we found that inferior OS and adverse clinical characteristics were significantly influenced by the number of mutated genes in the SRSF2/ASXL1/RUNX1 (S/A/R) panel (P<0.0001). In conclusion, the presence and number of mutated genes within the S/A/R panel are adversely associated with advanced disease and poor survival in KIT D816V(+) SM. On the basis of these findings, inclusion of molecular markers should be considered in upcoming prognostic scoring systems for patients with SM.

Molecular profiling of myeloid progenitor cells in multi-mutated advanced systemic mastocytosis identifies KIT D816V as a distinct and late event.

To explore the molecular profile and its prognostic implication in systemic mastocytosis (SM), we analyzed the mutation status of granulocyte-macrophage colony-forming progenitor cells (CFU-GM) in patients with KIT D816V(+) indolent SM (ISM, n=4), smoldering SM (SSM, n=2), aggressive SM (ASM, n=1), SM with associated clonal hematologic non-mast cell lineage disorder (SM-AHNMD, n=5) and ASM-AHNMD (n=7). All patients with (A)SM-AHNMD (n=12) carried 1-4 (median 3) additional mutations in 11 genes tested, most frequently TET2, SRSF2, ASXL1, CBL and EZH2. In multi-mutated (A)SM-AHNMD, KIT D816V(+) single-cell-derived CFU-GM colonies were identified in 8/12 patients (median 60%, range 0-95). Additional mutations were identified in CFU-GM colonies in all patients, and logical hierarchy analysis indicated that mutations in TET2, SRSF2 and ASXL1 preceded KIT D816V. In ISM/SSM, no additional mutations were detected and CFU-GM colonies were exclusively KIT D816V(-). These data indicate that (a) (A)SM-AHNMD is a multi-mutated neoplasm, (b) mutations in TET2, SRSF2 or ASXL1 precede KIT D816V in ASM-AHNMD,

[Neuroradiological focus on stroke imaging]. / Fokussierte neuroradiologische Diagnostik beim akuten Hirnschlag.

Stroke is heterogenous in its symptoms, which are also caused by various pathologies. Clinically the causing mechanism (bleeding or ischemia) of a new onset of neurological deficits can not reliably be distinguished. However, ischemia is four times more frequent than a bleeding causing neurological symptoms. Modern imaging technologies (computed assisted tomography or magnetic resonace imaging) and interventional techniques are a mainstay in diagnostics and management of acute onset of neurological symptoms. They can reliably distinguish between bleeding and stroke, especially taking newest technologies, such as perfusion studies and angiographies, into account. Neuroradiology with its interventional options has nowadays furthermore become an important tool in strokes and offers a local maneuver to retrieve the clotting pathology and even opens the therapeutic window for a delayed start of the therapy since symptom's onset beyong the conventional 4.5 hours window. Also risks of a therapy and which therapy option should be used can immediately be assessed.

[Spinal cord infarction]. / Spinaler Infarkt.

Infarction of the spinal cord can cause a variety of symptoms and neurological deficits because of the complex vascular supply of the myelon. The most common leading symptom is distal paresis ranging from paraparesis to tetraplegia caused by arterial ischemia or infarction of the myelon. Venous infarction, however, cannot always be distinguished from arterial infarction based on the symptoms alone.Modern imaging techniques, such as computed tomography angiography (CTA) and magnetic resonance angiography (MRA) assist in preoperative planning of aortic operations to reliably identify not only the most important vascular structure supplying the spinal cord, the artery of Adamkiewicz, but also other pathologies such as tumors or infectious disorders. In contrast to CT, MRI can reliably depict infarction of the spinal cord.

Enhanced Ras activity preserves dendritic size and extension as well as synaptic contacts of neurons after functional deprivation in synRas mice.

The monomeric GTP-binding protein p21Ras has been repeatedly implicated in neuronal stability and plastic changes of the adult nervous system. Recently, we have shown that expression of constitutively active Ras protein in transgenic synRas mice results in a significant increase in the dendritic size and complexity of differentiated pyramidal neurons as well as in increased synaptic connectivity. In the present study, we examined the organization of the vibrissae-barrel cortex in synRas mice and the effects of enhanced Ras activity on deprivation-induced dendritic reorganization after vibrissectomy. The results demonstrate a significant increase in vibrissae-barrel sizes and proportional spacing between barrels in synRas mice, suggesting that the neuronal target specificity of thalamocortical terminals is preserved. Accordingly, the arrangement of double bouquet cells at the borders of barrel columns ensuring functional distinctness is unchanged. Partial vibrissectomy is followed by significant dendritic regression of corresponding pyramidal neurons in the barrel cortex of wild-type mice, which, however, could not be observed in synRas mice. The results provide the first evidence for a role of Ras in preserving neuronal structure after functional deprivation in vivo.

Simian immunodeficiency virus lentivector corrects human X-linked chronic granulomatous disease in the NOD/SCID mouse xenograft.

X-linked chronic granulomatous disease (X-CGD) is a primary immunodeficiency caused by mutations in the phagocyte nicotinamide dinucleotide phosphate oxidase catalytic subunit gp91(phox). Gene therapy targeting hematopoietic stem cells (HSCs) can correct CGD, but permanent correction remains a challenge. Lentiviral vectors have become attractive tools for gene transfer, and they may have the potential to transduce very primitive HSCs. We used a self-inactivating RD114/TR-pseudotyped simian immunodeficiency virus (SIVmac)-based vector encoding human gp91(phox) for ex vivo transduction of peripheral blood-mobilized stem cells (PBSCs) from patients with X-CGD. In PBSCs from two patients, ex vivo transduction efficiencies of 40.5 and 46% were achieved, and correction of oxidase activity was observed in myeloid cells differentiating in culture. When transduced PBSCs from these patients were transplanted into nonobese diabetic/severe combined immunodeficient mice and compared to normal control, 10.5 and 7.3% of the human myeloid cells in bone marrow developing at 6 weeks from the human xenografts expressed the gp91(phox) transgene. Sustained functional correction of oxidase activity was documented in myeloid cells differentiated from engrafted transduced PBSCs. Transgene marking was polyclonal as assessed by vector integration site analysis. These data suggest that RD114/TR SIVmac-based vectors might be suitable for gene therapy of CGD and other hereditary hematologic diseases.

[Imaging of extradural spinal lesions]. / Bildgebung extraduraler Raumforderungen.

There is a wide variety of spinal extradural tumors. In addition to real neoplasms, degenerative diseases, congenital abnormalities and inflammatory disorders can be causes of extradural masses. Due to the bony boundary of the spinal canal, both benign as well as malignant masses can cause progressive neurological deficits including paraplegia. Most of the spinal tumors are benign (hemangioma of the vertebral body, degenerative diseases). In younger patients congenital abnormalities and primary tumors of the spine have to be considered, whereas in adults the list of differential diagnoses should include secondary malignancies such as metastases and lymphomas as well as metabolic disorders such as osteoporotic vertebral compression fracture and Paget's disease. Cross-sectional imaging techniques such as magnetic resonance imaging (MRI) and computed tomography (CT) of the spine often help to make a specific diagnosis of extradural spinal lesions and represent important tools for tumor staging and preoperative evaluation.

[Stroke]. / Hirninfarkt.

Today stroke represents a major medical and political problem in Western industrial nations. High demands need to be placed on the initial diagnostic work-up and therapeutic treatment to ensure that the patients benefit from the recent advancements achieved in diagnostic and therapeutic fields. According to the motto "time is brain" the clinical examination and imaging have to be performed within 60 min ("door to needle time") so that potential patients can be quickly treated with systemic or intra-arterial lysis. However, it should be taken into consideration that the selection of diagnostic imaging facilities depends on several factors such as infrastructure, the time remaining in the diagnostic window, and the severity of the clinical symptoms.

[Differential diagnosis of back pain]. / Differenzialdiagnose des Rückenschmerzes.

Back pain is one of the most frequent clinical pictures encountered in a physician's practice. It can pose a great burden on the individual and in addition have a multifactorial origin. It can be caused by intervertebral discs, vertebral joints, nerve roots, ligaments, sacroiliac joints, or a combination of the above. Back pain, as a symptom of a systemic disease, can also be a warning signal of grave disorders such as malignancies or in the event of aortic aneurysm. The well-considered choice of appropriate diagnostic procedures and suitable treatment requires a thorough knowledge of this multifactorial clinical picture.

[Postoperative syndrome after spine surgery]. / Postoperatives Syndrom nach Wirbelsäuleneingriffen.

Postoperative syndrome after spine surgery, i.e., symptoms or syndromes caused by complications or procedure-related consequences, is gaining more and more importance. Due to great improvements concerning imaging and operative techniques (microsurgery, instrumentation) the total number of spinal surgeries as well as their related complications are increasing. Procedure-related postoperative complications including neurological deficit syndromes can occur acutely or at a later date. Concerning imaging techniques for postoperative evaluation after spinal surgery there are several modalities available. Their indications depend on complex factors including initial pathology the surgery was performed for, kind of surgical technique (surgical approach, instrumentation), anatomy of the patient as well as the time between onset of symptoms and surgery. In cases of ambiguous findings, the combination of different imaging techniques can be instrumental.

[Spondylitis/spondylodiscitis]. / Spondylitis/Spondylodiszitis.

Spondylitis is an inflammation of the vertebral body. If the infection is manifested in the vertebral motor segment it is called spondylodiscitis, which can be divided into specific and nonspecific forms. It is clinically impressive that at the beginning of the disease, the patients who are quite often immunosuppressed suffer from localized, especially nocturnally exacerbated backache. The initial diagnostic work-up generally consists of clinical history, examination, laboratory tests, and (especially advanced) imaging findings. Although computed tomography still remains the most frequently used advanced imaging technique, magnetic resonance imaging is the golden standard for the diagnosis of spondylitis and spondylodiscitis.

[Skull base tumors]. / Tumoren der Schädelbasis.

Modern imaging techniques have great importance in the diagnosis and therapy of skull-base pathologies. Many of these lesions, especially in relation to their specific location, can be evaluated using CT and MR imaging. Tumors commonly found in the anterior skull base include carcinoma, rhabdomyosarcoma, esthesioneuroblastoma and meningioma. In the central cranial fossa, nasopharyngeal carcinoma, metastases, meningioma, pituitary adenoma and neurinoma have to be considered. The most common neoplasms of the posterior skull base, including the CP angle, are neurinoma, meningioma, nasopharyngeal carcinoma, chordoma and paraganglioma. One major task of imaging is the evaluation of the exact tumor extent as well as its relationship to the neighboring neurovascular structures. The purpose of this review is to recapitulate the most important anatomical landmarks of the skull base. The typical imaging findings of the most common tumors involving the skull base are also presented.

The efficacy of local anaesthesia for percutaneous epididymal sperm aspiration and testicular sperm aspiration.

A total of 37 percutaneous epididymal sperm aspiration (PESA) and/or testicular sperm aspiration (TESA) procedures were performed under local anaesthesia (LA) on 34 men between June and November 1996. Local anaesthesia was achieved by injecting 10 ml of 1% lignocaine solution along the sides of the vas deferens near the external inguinal ring (spermatic cord block). Sperm retrieval was successful in 92% of the procedures. Of the 37 procedures, in 29 the patients felt either no pain or mild discomfort while in six they experienced moderate but tolerable pain. Analgesia was incomplete in two procedures and was supplemented with i.v. sedation. Vasovagal reflex in two procedures was reversed by i.v. atropine. In 24 procedures patients felt relaxed, whilst in 13 they felt anxious. In 32 procedures the patients expressed overall satisfaction. If the procedure was to be repeated, after 29 procedures the patients requested LA again, while after four procedures they preferred i.v. sedation and after four were undecided. LA is adequate for PESA and TESA in a large proportion of patients. Prior discussion of LA technique with the patient is necessary. Back-up facilities for i.v. sedation and atropine should be available.