Intradural extraarachnoid sutureless technique combined with laminoplasty for indirect repair of ventral dural defects in spontaneous intracranial hypotension: technical note and case series.

BACKGROUND: There is a significant variance in surgical treatment strategies of ventral cerebrospinal fluid (CSF) leaks causing spontaneous intracranial hypotension (SIH). Posterior approaches might represent a preferable alternative to the more invasive anterior and lateral routes, as long as the spinal cord is not exposed to harmful manipulation. The aim of this technical note is to report and illustrate a new surgical technique using an intradural extraarachnoid sutureless technique via laminoplasty for indirect repair of ventral CSF leaks causing intractable SIH symptoms. METHODS: The surgical technique is described in a step by step fashion. Between May 2018 and May 2020, five patients with ventral spinal CSF leaks were operated on, utilizing this technique. All dural defects were located at the level of the thoracic spine. A retrospective review on demographic and radiological findings, symptoms, outcome, and follow-up was performed. RESULTS: The intra- and postoperative course was uneventful in all patients with no surgery-related complications. Three patients recovered completely at discharge, while neurological symptoms significantly improved in two patients. A postoperative MRI of the spine was obtained for all patients, demonstrating regressive signs of CSF leak. CONCLUSION: Based on the presented case series, this intradural extraarachnoid sutureless technique combined with laminoplasty seems to be a safe and effective option for indirect repair of ventral dural defects in SIH. In our opinion, it represents a valid alternative to traditional more aggressive approaches.

Severe underquantification of HIV-1 group O isolates by major commercial PCR-based assays.

HIV-1 diversity poses major challenges to viral load assays because genetic polymorphisms can impede nucleic acid detection. In addition to the on-going viral diversification within the HIV-1 group M pandemic, HIV-1 genetic diversity is further increased by non-group M infections, such as HIV-1 groups O (HIV-1-O), N and P. We here conducted a systematic evaluation of commercially available PCR assays to detect HIV-1-O isolates. We collected 25 primary HIV-1-O isolates covering all genetic clusters within HIV-1-O. Subsequently, this panel of isolates was tested on eight commercially available quantitative and five qualitative HIV-1 PCR-based assays in serial dilutions. Sequence analyses were performed for severe cases of underquantification or lack of detection. We observed differences between the assays in quantification that depended on the HIV-1-O isolate's subgroup. All three tested HIV-1-O subgroup IV isolates were underquantified by the Roche CAP/CTM >800-fold compared to the Abbott RealTime assay. In contrast, the latter assay underquantified several subgroup I isolates >200-fold. Notably, the Xpert HIV-1 Viral Load test from Cepheid failed to detect two of the HIV-1-O isolates, whereas the Roche Cobas 8800 assay readily detected all isolates. Comparative sequence analyses identified polymorphisms in the HIV-1-O long-terminal repeat and integrase genes that likely underlie inadequate nucleic acid amplification. Potential viral load underquantification should be considered in therapeutic monitoring of HIV-1-O-infected patients. Pre-clinical assessments of HIV-1 diagnostic assays could be harmonized by establishing improved and internationally standardized panels of HIV-1 isolates that cover the dynamic diversity of circulating HIV-1 strains.

The probability of restenosis, contralateral disease progression, and late neurologic events following carotid endarterectomy: a long-term follow-up study.

BACKGROUND: Most studies that have reported on the progression of ipsilateral and/or contralateral internal carotid artery (ICA) stenosis are restricted to a few years. METHODS: Based on a single-center carotid endarterectomy (CEA) registry, we sought all patients with CEA for symptomatic high-grade ICA stenosis between 1970 and 2002. 361 CEA patients (mean age 66 years, 73% male) with annual carotid ultrasound and clinical follow-up were identified. Kaplan-Meier analysis was used to estimate the occurrence of (i) progressive ICA stenosis or restenosis of either the operated or contralateral side, and (ii) cerebrovascular events over time of either the operated or contralateral side. RESULTS: Progressive ICA disease was more likely on the contralateral than on the ipsilateral ICA (hazard ratio 2.71; CI 1.8-4.1, p < 0.001). After 5 years, the probability for progressive ICA disease was 5.2% for the ipsilateral versus 15.8% for the contralateral ICA. After 15 years, the likelihood was 37% for both sides. In the presence of progressive restenosis of the ipsilateral ICA, the 20-year probability of further ischemic cerebrovascular events was 50% compared to 18% in patients without ICA disease progression. For the contralateral ICA, the probability of further ischemic events was 24.5% in patients with ICA disease progression compared to 9.6% without ICA disease progression (15 years). CONCLUSION: 15 years after CEA, one third of the patients can be expected to develop progressive ICA disease. While ICA disease progression seems to be more prominent on the contralateral ICA within the first years, this difference fades out after 15 years. One out of 2 patients with ipsilateral ICA disease progression can be expected to have a recurrent cerebral ischemic event within 15 years. It remains to be determined whether consequent application of high-dose statins, optimal blood pressure management and antithrombotic therapy can reduce this rate.

Acute paraplegia after myelography: decompensation of a herniatad thoracic disc.

A 71-year-old patient presented with low back pain and slowly progressive weakness of both legs. Within a few hours after lumbar myelography, paraplegia below level L2 evolved. MR-imaging revealed a discogenic stenosis at level Th10/11. Immediate decompression by costo-transversectomy led to reversal of the neurological deficits.

[Primary cerebellar T-cell lymphoma]. / Primäres zerebelläres T-Zell-Lymphom.

Primary central nervous system T-cell lymphomas are rare and have to be differentiated from reactive lesions. It is therefore essential to use all possible tools to establish the diagnosis, including immunohistochemistry, molecular genetic analysis, and/or cytogenetic methods. In this paper we present the case of a primary cerebellar T-cell lymphoma in a 50-year-old man; a clonal T-cell receptor gene rearrangement was documented. After two cycles of methotrexate therapy the patient developed Pneumocystis carinii-induced pneumonia, dying 10 weeks after his diagnosis. The autopsy did not reveal any residual tumour.

The tumour suppressor protein p53 can repress transcription of cyclin B.

The tumour suppressor protein p53 has functions in controlling the G(1)/S and G(2)/M transitions. Central regulators for progression from G(2) to mitosis are B-type cyclins complexed with cdc2 kinase. In mammals two cyclin B proteins are found, cyclin B1 and B2. We show that upon treatment of HepG2 cells with 5-fluorouracil or methotrexate, p53 levels increase while concentrations of cyclin B2 mRNA, measured by RT-PCR with the LightCycler system, are reduced. In DLD-1 colorectal adenocarcinoma cells (DLD-1-tet-off-p53) cyclin B1 and B2 mRNA levels drop after expression of wild-type p53 but not after induction of a DNA binding-deficient mutant of p53. Analysis of the cyclin B2 promoter reveals specific repression of this gene by p53. Transfection of wild-type p53 into SaOS-2 cells shuts off transcription from a cyclin B2 promoter-luciferase construct whereas a p53 mutant protein does not. The cyclin B2 promoter does not contain a consensus p53 binding site. Most of the p53-dependent transcriptional responsiveness resides in its 226 bp core promoter. Taken together with earlier observations on p53-dependent transcription of cyclin B1, our results suggest that one way of regulating G(2) arrest may be a reduction in cyclin B levels through p53-dependent transcriptional repression.

Expression of p73 and its relation to histopathology and prognosis in hepatocellular carcinoma.

BACKGROUND: The protein p73, the first identified homologue of the tumor suppressor gene p53 (also known as TP53), has been shown to induce apoptosis (programmed cell death), but its function in tumor development has not been established. This study was undertaken to investigate the expression of p73 in liver tissue of patients with hepatocellular carcinoma (HCC) and to determine whether this expression has any impact on prognosis. METHODS: In situ hybridization and immunohistochemistry for the detection of p73 RNA transcripts and protein, respectively, were performed in tissues from 193 patients with curatively (R0-) resected HCC. Patients receiving liver transplantation were excluded. The results obtained were analyzed with respect to their association with pathohistologic stage, Edmondson grade, p53 expression status and several histopathologic factors of possible prognostic value, and, finally, with patient survival. RESULTS: RNA transcripts encoding p73 were detected by in situ hybridization in tumor cells but not in stromal, endothelial, or inflammatory cells or in cholangiocytes. Transcripts were also found occasionally in non-neoplastic hepatocytes. By immunohistochemistry, we detected p73 protein in 61 (32%) of the 193 carcinomas examined. Positive immunohistochemical staining was confined to the cell nucleus. Univariate survival analysis showed that p73 expression status was statistically significantly related to prognosis (two-sided P<.0001). Patients with p73-positive tumors had a poorer prognosis than those with p73-negative carcinomas. Multivariate Cox survival analysis identified the age of the patient, p73 expression status, co-existing cirrhosis, and Edmondson grade as independent prognostic factors. CONCLUSION: The protein p73 is overexpressed by a subset of HCCs and could serve as a useful indicator of prognosis in patients with this disease.

The cyclin B2 promoter depends on NF-Y, a trimer whose CCAAT-binding activity is cell-cycle regulated.

Cyclin B2 is a regulator of p34cdc2 kinase, involved in G2/M progression of the cell cycle, whose gene is strictly regulated at the transcriptional level in cycling cells. The mouse promoter was cloned and three conserved CCAAT boxes were found. In this study, we analysed the mechanisms leading to activation of the cyclin B2 CCAAT boxes: a combination of (i) genomic footprinting, (ii) transfections with single, double and triple mutants, (iii) EMSAs with nuclear extracts, antibodies and NF-Y recombinant proteins and (iv) transfections with an NF-YA dominant negative mutant established the positive role of the three CCAAT sequences and proved that NF-Y plays a crucial role in their activation. NF-Y, an ubiquitous trimer containing histone fold subunits, activates several other promoters regulated during the cell cycle. To analyse the levels of NF-Y subunits in the different phases of the cycle, we separated MEL cells by elutriation, obtaining fractions >80% pure. The mRNA and protein levels of the histone-fold containing NF-YB and NF-YC were invariant, whereas the NF-YA protein, but not its mRNA, was maximal in mid-S and decreased in G2/M. EMSA confirmed that the CCAAT-binding activity followed the amount of NF-YA, indicating that this subunit is limiting within the NF-Y complex, and suggesting that post-transcriptional mechanisms regulate NF-YA levels. Our results support a model whereby fine tuning of this activator is important for phase-specific transcription of CCAAT-containing promoters.

Dynamics of serum procalcitonin in patients after major neurosurgery.

Classical markers of infection cannot differentiate reliably between inflammation and infection after neurosurgery. This study investigated the dynamics of serum procalcitonin (PCT) in patients following major neurosurgery. PCT concentrations remained < 0.2 ng/mL during the post-operative course. In contrast, leukocyte and neutrophil counts, as well as C-reactive protein (CRP) levels, increased significantly post-operatively (leukocytes, range 7.1-23.7 x 10(9)/L, p < 0.001; neutrophils, range 70.8-94.5%, p < 0.001; CRP, median 14 mg/L, range 3-95 mg/L, p < 0.001). Analysis of PCT levels using assays with improved sensitivity may be useful in the diagnosis of neurosurgical patients with post-operative fever of unknown origin.

Locoregional regulatory peptide receptor targeting with the diffusible somatostatin analogue 90Y-labeled DOTA0-D-Phe1-Tyr3-octreotide (DOTATOC): a pilot study in human gliomas.

Human gliomas, especially of low-grade type, have been shown to express high-affinity somatostatin receptor type 2 (J-C. Reubi et al., Am. J. Pathol, 134: 337-344, 1989). We enrolled seven low-grade and four anaplastic glioma patients in a pilot study using the diffusible peptidic vector 90Y-labeled DOTA0-D-Phe1-Tyr3-octreotide (DOTATOC) for receptor targeting. The radiopharmakon was locoregionally injected into a stereotactically inserted Port-a-cath. DOTATOC competes specifically with somatostatin binding to somatostatin receptor type 2 in the low nanomolar range as shown by a displacement curve of 125I-[Tyr3]-octreotide in tumor tissue sections. Diagnostic (111)In-labeled DOTATOC-scintigraphy following local injection displayed homogeneous to nodular intratumoral vector distribution. The cumulative activity of regionally injected peptide-bound 90Y amounted to 370-3300 MBq, which is equivalent to an effective dose range between 60 +/- 15 and 550 +/- 110 Gy. Activity was injected in one to four fractions according to tumor volumes; 1110 MBq of 90Y-labeled DOTATOC was the maximum activity per single injection. We obtained six disease stabilizations and shrinking of a cystic low-grade astrocytoma component. The only toxicity observed was secondary perifocal edema. The activity:dose ratio (MBq:Gy) represents a measure for the stability of peptide retention in receptor-positive tissue and might predict the clinical course. We conclude that SR-positive human gliomas, especially of low-grade type, can be successfully targeted by intratumoral injection of the metabolically stable small regulatory peptide DOTATOC.

The course of the terminal phase in patients with amyotrophic lateral sclerosis.

The fear of "choking to death" is on the mind of most patients suffering from amyotrophic lateral sclerosis (ALS). So far, however, there have been no systematic surveys concerning the dying phase in a general ALS population. We therefore performed a structured telephone interview with the relatives of 121 patients who died from ALS and were followed by the Motor Neuron Outpatient Clinic of the Department of Neurology, University of Munich, Germany. These data are compared with those obtained by a retrospective analysis of medical records of 50 ALS patients who were followed by the Wisdom Hospice, Rochester, UK. The data show that most ALS patients (Germany 88%, UK 98%) died peacefully, and no patient "choked to death". The symptoms most frequently reported for the last 24 hours were dyspnoea, coughing, anxiety and restlessness. Around half (G 55%, UK 52%) of the patients died at home. The main palliative measures in place during the terminal phase were: home mechanical ventilation (G 21%, UK 0%), percutaneous endoscopic gastrostomy (G 27%, UK 14%), morphine (G 27%, UK 82%) and benzodiazepines (G 32%, UK 64%). The use of these palliative measures was judged to be beneficial by almost all relatives. These data support the hypothesis of a peaceful death process in ALS and should be communicated to patients and their relatives, at the latest after the onset of dyspnoea, to relieve unwarranted fears.

Patients' assessment of quality of life instruments: a randomised study of SIP, SF-36 and SEIQoL-DW in patients with amyotrophic lateral sclerosis.

The evaluation of quality of life (QoL) plays an increasingly important role in clinical research and drug trials in ALS. However, most of the scales employed so far are based on a fixed external value system, and may therefore not reflect the patients' subjective perception of QoL accurately. In addition, many ALS patients complain about the psychological distress inflicted by QoL questionnaires which focus on functional status, as they constantly remind patients of their deterioration. We therefore asked 42 ALS patients to assess, using visual analogue scales, their subjective perception of the validity of three QoL instruments as well as the emotional distress caused by them. The scales were: the Sickness Impact Profile (SIP), the Short Form 36 (SF-36), and the Schedule for the Evaluation of Individual QoL-Direct Weighting (SEIQoL-DW). Patients were examined at least three times at two-month intervals. The SIP was filled out by all patients, the SF-36 and the SEIQoL-DW were assigned at random. The validity of the SEIQoL-DW was rated higher than that of the SIP (p<0.001) and of the SF-36 (p<0.001). The SIP imparted a higher emotional distress to patients than the SEIQoL-DW (p<0.005), with a trend in the same direction for the SF-36 (p=0.082). The most frequently mentioned QoL-relevant domains in the SEIQoL-DW were family (100%), health (53%), and profession (50%). These results should prompt further discussion and investigation on the most appropriate way to assess QoL in patients with ALS.

The use of alternative medicine by patients with amyotrophic lateral sclerosis.

The use of complementary and alternative medicine (CAM) is increasing in all industrialised countries, especially in patients with chronic and incurable diseases. However, no data are available on the use of CAM by patients with amyotrophic lateral sclerosis (ALS). The German Association for Neuromuscular Diseases (DGM) mailed out a questionnaire on CAM to 350 ALS patients, 171 of whom completed and returned the survey (response rate 49%). The use of CAM was reported by 92 patients (54%). There were no significant demographic differences between users and nonusers. The patients used 73 different methods or substances; some tried up to 11 different treatments. The most widely used methods were: acupuncture (47%), homeopathy (40%), naturopathy (24%) and esoteric treatments (20%). The lower the patients' expectations from CAM, the better was the subjectively perceived effect. In most cases (60%), alternative treatments were performed by a physician. Patients spent on average 4000 (approximately US$4500) on CAM, generally without reimbursement. CAM is most often used in addition to conventional treatments and may be part of the patients' coping strategy. Open communication between patients and physicians is essential to warn the patients of medically or financially hazardous treatments. Future research should look at the possible palliative effects of CAM on symptom control and quality of life of patients and families.

Stimulation of subthalamic fibre tracts reduces dyskinesias in STN-DBS.

Rarely, the postoperative management of patients with subthalamic deep brain stimulation (STN-DBS) is complicated by pharmacologically intractable dyskinesias. Here we report that in three of these patients additional stimulation of a proximal contact located within the subthalamic white matter may lead to a significant reduction of dyskinesias associated with STN-DBS. We propose that pallidofugal fiber tracts play a major role in the etiopathology of dyskinesias and their blockade through DBS may explain our observations.

Cross-cultural variation in mental health at end of life in patients with ALS.

OBJECTIVE: To examine mental health at the end of life among patients with ALS in three countries: Israel, Germany, and the United States. METHODS: Patients met criteria for definite or probable ALS and had forced vital capacity (FVC) <60% of predicted. Patients completed nonsomatic items from the Beck Depression Inventory and visual analogue scale ratings. RESULTS: The three sites contributed a total of 92 patients; 60 died during follow-up. Patients at the three sites did not differ significantly in sociodemographic features or ALS Functional Rating Scale-Revised summary disability score; sites differed in use of nasal ventilation but not percutaneous esophageal gastrostomy (PEG) tube placement. In analyses that adjusted for disability and use of nasal ventilation, patients at the three sites differed in reports of pessimism and suffering; American patients reported the least distress and Israeli patients the most. In analyses limited to people who died, similar patterns emerged, with wish to live greatest in Americans and least among Israelis. These models adjusted for disability and days until death. CONCLUSIONS: Cultural factors may affect mental health at the end of life in patients with ALS.

[Intraspinal malformations. Tethered cord syndrome]. / Intraspinale Missbildungen--Tethered Cord Syndrom.

The importance of intraspinal malformations associated with "tethered cord" (attachment of the spinal cord) has increased in recent years, because of better imaging methods using nuclear magnet resonance (MRI). Orthopedic malformations such as club feet, equinus deformity, lordosis, hip dislocation, kyphosis, and differences of leg lengths, which up till now have been mostly treated by orthopedic surgeons, are usually first examined for congenital anomalies. According to the results of this examination, a neurosurgical operation for untethering is performed. The aim of our study is to define spinal malformations more exactly and to elucidate their importance for orthopedics. In addition, indications for operating, operative aims, diagnosis, therapy and follow-up are discussed. Examples of our results are shown, and the significance for interdisciplinary cooperation is emphasized.

[The results of percutaneous diskectomy. The course of pain, work capacity and therapy failure]. / Ergebnisse der perkutanen Diskektomie. Schmerzverlauf, Arbeitsfähigkeit und Therapieversagen.

In a prospective study extending from November 1989 to December 1992 percutaneous discectomy was carried out in 50 patients (26 men, 24 women, mean age 41 [19-73] years). The aim of the study was to ascertain the efficacy of this new mode of treatment, and its indications. The patients selected for the procedure had chronic, therapy-resistant lumboradicular pain syndrome of at least six weeks' duration; imaging procedure had to show a "bulging disc" and neurological deficits had to be no more than minor. During the subsequent follow up period of 22 +/- 9.6 months 35 of the 50 patients did not require any further surgery; 24 of them (69%) resumed full work while seven (20%) regained partial (50%) working capacity. However, the operation proved ineffective in four of these 35 patients (11%). Fourteen of the 50 patients (28%) had persistent pain and required revision by open classical discectomy; seven of them resumed full work and one regained 50% working capacity. The most frequent findings at this revision were stenosis of the subarticular recess in combination with persistent forward bulging of the longitudinal ligament and anulus fibrosus (n = 7), calcification of the posterior longitudinal ligament (n = 1) and an intervertebral disc sequestrum which gave a false negative results on discography (n = 2). In another case there was a genuine recurrence 35 months after a successful percutaneous procedure; this was treated successfully by open operation. When performed at the level L5/S1, the procedure gave unsatisfactory results in five out of six cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Diagnosis and management of abscesses in the basal ganglia and thalamus: a survey.

A review is made of the current management strategies of abscesses in basal ganglia and thalamus, based on a review of the literature and three of our own cases. Clinical picture, aetiology, diagnostic, surgical treatment and outcome are discussed. Stereotactic abscess puncture in combination with temporary drainage and rinsing of the abscess cavity in combination with systemic medication of antibiotics has become the management of choice with satisfactory results.

Regulation and possible function of beta-catenin in human monocytes.

In this study, we demonstrate that adherence factors, serum constituents, LPS, and zymosan are capable of inducing a cellular accumulation of beta-catenin in human monocytes. Whereas adherence-dependent accumulation of beta-catenin can be blocked by wortmannin, an inhibitor of phosphatidylinositol 3-kinase, accumulation induced by the remaining stimuli cannot be prevented by inhibition of phosphatidylinositol 3-kinase, implying the involvement of beta-catenin in other not yet described signal transduction pathways. A role of beta-catenin in adherence-dependent processes by interacting with classical cadherins can be excluded as we could not detect cadherins in monocytes. To test whether it is possible that beta-catenin interacts with LEF/TCF (lymphoid enhancer factor/T cell factor) transcription factors, we studied the expression of this protein family. TCF-4 was identified as the LEF/TCF transcription factor present in human monocytes. However, neither cellular induction of beta-catenin nor cotransfection experiments with beta-catenin conducted in the monocytic cell line THP-1 resulted in the activation of a LEF/TCF-dependent promoter, suggesting the requirement of additional signals. Concurrent with this suggestion, we found that LPS and zymosan, two physiological inducers of beta-catenin, caused an increase in the expression of genes that are positively regulated by beta-catenin.

[Intermittent paraparesis as manifestation of a bilateral chronic subdural hematoma]. / Fluktuierende Paraparese als Manifestation eines bilateralen chronischen Subduralhämatoms.

Chronic subdural haematomas are mainly related to slight or moderate head trauma with consecutive lesion of bridge or cortical veins and bleeding in the subdural space. Further predisposing factors are known impairment of coagulation (coagulopathies, treatment with anticoagulants, alcohol abuse), risk factors for degenerative disease of the arteries (diabetes mellitus, arterial hypertension), and development of pressure gradients (hydrocephalus, epileptic seizures, lumbar puncture, CSF drainage and cerebral atrophy). Chronic subdural haematomas appear bilaterally in 20 to 25% of cases. We report on a 69-year-old male with a 4-day history of intermittent, proximal, painless paraparesis (BMA grade M2-5) without a trigger event. Sensibility was normal in all qualities and vigilance was not disturbed. Computed tomography of the neurocranium revealed a bitemporally located chronic subdural haematoma with extension to parietal on both sides. Trepanation was performed over the tuber parietale and temporoparietally on both sides, with release of 150 ml fluid. The neurologic deficits regressed totally within 12 hours postoperatively. To the best of our knowledge, we are the first to describe the clinical paradox of intermittent, painless paraparesis with preserved sensibility and without disturbances of vigilance, as manifestation of a chronic subdural haematoma possibly leading to impairment of cerebral blood flow in the area of the middle cerebral artery. Small changes in systemic blood pressure lead to changes in cerebral perfusion pressure due to vessel compression by the haematoma, thus explaining the intermittent character of the clinical presentation.