Bevacizumab may improve quality of life, but not overall survival in glioblastoma: an epidemiological study.

Background: The vascular endothelial growth factor antibody bevacizumab (Avastin®), received approval for the treatment of recurrent glioblastoma in many countries including the USA and Switzerland, but not the European Union, in 2009. Here, we explored the hypothesis that the approval of bevacizumab improved outcome with glioblastoma on a population level. Patients and methods: The prognostic significance of epidemiological, molecular genetic, and clinical data including treatment for glioblastoma patients diagnosed from 2010 to 2014 in the Canton of Zurich, Switzerland, was retrospectively analyzed using log-rank test and Cox proportional hazards models. Data were compared with data for the years 2005-2009. Results: In total, 310 glioblastoma patients were identified in the years 2010-2014. Median overall survival was 13.5 months for patients with known isocitrate dehydrogenase (IDH) wild-type (wt) (IDH1R132H-non-mutant) tumors (N = 248), compared with 11.3 months for IDH wt patients (P = 0.761) before (2005-2009). In the IDH wt cohort, bevacizumab use at any time increased from 19% in 2005-2009 to 49% in 2010-2014. Multivariate analysis did not identify bevacizumab exposure at any time to be associated with survival. Yet, upon the second-line treatment, baseline doses of corticosteroids were reduced by more than half in 83% of patients on bevacizumab compared with 48% of the patients treated with bevacizumab-free regimens (P = 0.007). Conclusion: This epidemiological study of a small, but clinically well-annotated patient cohort fails to support the assumption that the strong increase of bevacizumab use since 2010 improved survival in glioblastoma although clinical benefit associated with decreased steroid use may have been achieved.

[Unusual course of a planned lumbar microdiscectomy]. / Ungewöhnlicher Verlauf einer elektiv geplanten lumbalen Bandscheibenoperation.

We report the case of a 30-year-old female patient who underwent unilateral transverse sinus stenosis stenting due to a newly diagnosed idiopathic intracranial hypertension (Pseudotumor cerebri) with symptoms of papilledema, decreased visual acuity and headache. Resolution of the symptoms and improvement of magnetic resonance and ophthalmiologic findings could be documented.

Wide-field optical coherence tomography: imaging of biological tissues.

We describe a two-dimensional optical coherence tomography technique with which we were able to obtain multiple longitudinal slices of a biological sample directly in a single Z scan. The system is based on a femtosecond Cr4+:forsterite laser and an infrared camera for wide-field imaging of the sample with a depth resolution of 5 microm. With this imaging apparatus we were able to investigate human skin and mouse ear samples and to observe the different constitutive tissues.

Longitudinal imaging in biological tissues with a single laser shot correlation system.

We demonstrate the potential of a new optical imaging system to directly obtain a longitudinal slice of a biological sample. The system, based on a single-shot optical correlator, operates a time-to-space conversion and an optical time-gating by sum-frequency generation in a nonlinear crystal. Owing to the high speed acquisition of the technique, internal structures of in-vivo tissues can be imaged at video rate.With this apparatus, we recorded longitudinal images of ex vivo mouse ear and in vivo human skin with a depth resolution of approximately 15 microm.

The surveillance mechanism of the spindle position checkpoint in yeast.

The spindle position checkpoint in Saccharomyces cerevisiae delays mitotic exit until the spindle has moved into the mother-bud neck, ensuring that each daughter cell inherits a nucleus. The small G protein Tem1p is critical in promoting mitotic exit and is concentrated at the spindle pole destined for the bud. The presumed nucleotide exchange factor for Tem1p, Lte1p, is concentrated in the bud. These findings suggested the hypothesis that movement of the spindle pole through the neck allows Tem1p to interact with Lte1p, promoting GTP loading of Tem1p and mitotic exit. However, we report that deletion of LTE1 had little effect on the timing of mitotic exit. We also examined several mutants in which some cells inappropriately exit mitosis even though the spindle is within the mother. In some of these cells, the spindle pole body did not interact with the bud or the neck before mitotic exit. Thus, some alternative mechanism must exist to coordinate mitotic exit with spindle position. In both wild-type and mutant cells, mitotic exit was preceded by loss of cytoplasmic microtubules from the neck. Thus, the spindle position checkpoint may monitor such interactions.

The cortical protein Num1p is essential for dynein-dependent interactions of microtubules with the cortex.

In budding yeast, the mitotic spindle moves into the neck between the mother and bud via dynein-dependent sliding of cytoplasmic microtubules along the cortex of the bud. How dynein and microtubules interact with the cortex is unknown. We found that cells lacking Num1p failed to exhibit dynein-dependent microtubule sliding in the bud, resulting in defective mitotic spindle movement and nuclear segregation. Num1p localized to the bud cortex, and that localization was independent of microtubules, dynein, or dynactin. These data are consistent with Num1p being an essential element of the cortical attachment mechanism for dynein-dependent sliding of microtubules in the bud.

Real-time two-dimensional imaging in scattering media by use of a femtosecond Cr(4+):forsterite laser.

An original femtosecond Cr(4+):forsterite laser source associated with a nonlinear optical correlator was used for imaging through scattering media with 1220-nm light. The system, which operates as an ultrafast optical gate by sum-frequency generation in a nonlinear crystal, was able to detect the light reflected from a resolution chart hidden in a turbid medium, at an attenuation of as much as 15 mean free paths. When the object was illuminated with a collimated beam, real-time two-dimensional images were obtained, with a maximum transverse resolution of ~20 microm.

[Axillary nerve paralysis after playing squash. A case report]. / Axillarisparese nach Squash-Spielen. Ein Fallbericht.

A 27-year-old otherwise healthy male presented with an isolated but complete axillary nerve palsy after excessive squash playing. When repeated electromyographic investigations showed no signs of reinnervation in the deltoid muscle, surgery was performed in order to restore nerve function. Intraoperatively, the nerve showed a short segment of thinning about 2 cm distally the nerve's origin from the posterior fascicle. As intraoperative electrophysiological testing was also negative (no electrically evoked nerve action potentials across the lesion) the suspicious nerve segment was resected and nerve continuity restored by sural grafts. Histologically, no intact nerve structures could be found at the site of the thinning. Most likely the lesion was caused by traction forces. Follow-up studies showed reinnervation of deltoid function over time.

Radiological investigations and intra-operative evoked potentials for the diagnosis of nerve root avulsion: evaluation of both modalities by intradural root inspection.

Fourteen patients with traumatic brachial plexus injuries underwent intradural inspection of cervical nerve roots to evaluate radiological and intra-operative electrophysiological findings concerning cervical nerve root avulsion from the spinal cord. Four neurosurgeons of our department assessed independently from each other both myelography and CT-myelography concerning intradural nerve root lesions. Each neurosurgeon assessed a total of 26 cervical nerve roots. Two investigators assessed 6/26 and 2 investigators 7/26 nerve roots falsely concerning ventral or/and dorsal root lesions compared with the findings on intradural inspection (23% and 27% false findings). There was a considerable variance concerning the assessibility and findings among the 4 neurosurgeons. Reconstructive surgery was performed after a mean interval of 6.5 months following trauma and 2 weeks following intradural inspection. After exposure of the brachial plexus and the cervical nerve roots in question via a ventral approach, 13 cervical nerve roots were stimulated electrically close to the neuroforamen and cortical evoked potentials (root-SEPs) were recorded from the contralateral postcentral region. All 5 roots with SEPs were intact (no root lesion) and all 8 roots without SEPs showed interrupted (ventral or/and dorsal) rootlets on intradural inspection. Our results demonstrate that false radiological findings concerning root lesions are possible. Intra-operative root-SEPs seem to be a useful aid for evaluation of cervical nerve root lesions. However, more electrophysiological data are necessary to ascertain, if this modality is able to replace intradural inspection in unclear radiological cases in the future.

[Painful paresthesia after removal of the sural nerve for autologous nerve transplantation]. / Schmerzhafte Paraesthesien nach Entnahme des Nervus suralis zur autologen Nerventransplantation.

The sural nerve is the most common nerve serving as a donor in an autologeous nerve grafting procedure. However, there is a certain risk for the development of painful paraesthesias at the donor site. Patients in whom a short segment of the sural nerve was resected are suspected to have a greater risk. In a retrospective study we investigated the incidence of painful paraesthesias following removal of a segment of the sural nerve for a grafting procedure. The study includes 41 patients, who were followed at least for one year after surgery (mean 30 months). 9 patients (22%) complained of persisting painful paraesthesias at the donor site suggesting a neuroma at the proximal stump of the sural nerve. The comparison of the length of the nerve segment harvested for grafting shows a tendency for patients with shorter segments having a greater risk to develop painful paraesthesias. However, the difference between the two groups was statistically not significant.

54-fs, 1-GW, 1-kHz pulse amplification in Cr:forsterite.

30-fs pulses at 1.22 microm are produced by a self-mode-locked Cr:forsterite laser and amplified in a Cr:forsterite regenerative amplifier by a chirped-pulse amplification technique. 54-fs, 1-GW pulses at a 1-kHz repetition rate are obtained.

Value of nerve action potentials in the surgical management of traumatic nerve lesions.

OBJECTIVE: The goals of the study were to investigate the value of intraoperative electrically evoked nerve action potentials (NAPs) in the surgical treatment of traumatic peripheral nerve injuries (nerve lesions in continuity). METHODS: Sixty-four patients with 76 traumatic nerve lesions in continuity were investigated intraoperatively by stimulating and recording NAP from the whole nerve across the suspected lesion site. Among the 76 nerves (nerve lesions) were 43 with incomplete and 33 with complete loss of function. In cases (nerves) with complete loss of function (n = 33), the surgical procedure (external neurolysis, internal neurolysis, or nerve repair) was performed according to the microscopic aspect of the nerve and the result of the intraoperative electrophysiological testing. In cases (nerves) with incomplete loss of function (n = 43), the surgical procedure was performed solely according to the microscopic aspect of the nerve and independently from the result of the intraoperative electrophysiological testing. RESULTS: Of 43 nerves with incomplete loss of function, we were able to record reproducible NAPs in 41 (95%) across the lesion site, thus demonstrating a high reliability of the method. Of 33 nerves with complete loss of function, a reproducible NAP could be recorded only in 3. Assuming an axonotmetic lesion in regeneration, we did nothing else on the nerve with excellent clinical results (full recovery). Of the remaining nerves with no NAP, 24 showed a caliber shift of the nerve (in 20 cases a thickening of the nerve, suggesting a neuroma in continuity). A grafting procedure was performed, and the histological evaluation revealed a neurotmetic lesion. However, in six patients with no NAP, there was no clear caliber shift of the nerve. The epineurium was opened and an internal neurolysis performed showing fascicles in continuity. Three patients had good and three had partial (but useful) recovery. CONCLUSIONS: In nerve lesions in continuity with complete loss of nerve function, intraoperative NAPs are able to detect axonotmetic lesions in regeneration. Thus, unnecessary further surgical procedures can be avoided. On the other end of the spectrum, no recordable NAP together with a caliber shift of the nerve (suggesting a neuroma in continuity) may facilitate the surgeon's decision for a grafting procedure without a time-consuming internal neurolysis. But there is also evidence from our data that not every nerve lesion in continuity without a NAP needs to be grafted.

[Experiences with endoscopic surgery in treatment of carpal tunnel syndrome. Preliminary results of a prospective study]. / Erfahrungen mit der endoskopischen Operation zur Behandlung des Karpaltunnelsyndroms. Vorläufige Ergebnisse einer prospektiven Studie.

Endoscopic carpal tunnel release is a new technique for treatment of carpal tunnel syndrome. The benefits of this procedure are a small skin wound with less local pain, the fact that the hand can quickly be used again, and earlier return to work or other activities. We present the preliminary results of the 3-month follow-up of 88 patients out of a prospective study of 100 patients. All patients were operated on using the one-port technique. Six additional decompressions had to be abandoned and open release was performed. Of the patients with pain, 73.6% (68/88) were completely pain-free and in 13.2% (9/68) pain improved in more than 50%. Subjective symptoms like paresthesia and numbness of the hand disappeared completely in 77.2% (64/83). Sensory deficits disappeared in 50% (33/66). Ten of 17 patients with preoperative paresis of the abductor pollicis brevis muscle and 11/14 with paresis of the opponens pollicis muscle had normal motor function 3 months after the operation. The complication rate concerning nerve lesions was 2.3%. The return to work time was 21 days (range 3-49 days). According to clinical symptoms, our preliminary results do not seem to have any benefits compared to the conventional open technique, and the costs for the endoscopic procedure are markedly higher. The complication rate after the learning curve period is approximately the same as open carpal tunnel release.

Peripheral nerve schwannomas--an analysis of 16 patients.

16 patients with peripheral nerve neurinomas (benign schwannomas) were operated upon in our hospital between 1990-1995. The largest tumours were found on proximal segments of peripheral nerves (brachial plexus: 15 cm, sciatic nerve: 20 cm). The average duration of symptoms was 1 1/2 years (range: 3 months-15 years). Pain or painful paraesthesias were the main complaints (13/16). Postoperatively, 9 patients were painfree while 4 improved. Similarly, neurological deficits were favourably influenced by the operation: Out of 5 patients with motor deficits 4 had complete, 1 patient had partial recovery. One out of 4 patients with sensory deficits had complete recovery, 2 remained unchanged, while 1 worsened. Two patients developed new motor and 6 patients new sensory deficits, which (in the course of time) did not disappear completely. New deficits developed predominantly in patients with large tumours or longstanding symptoms. Tumour recurrences were not seen during the follow-up period of 23 months. Our findings revealed that in the majority of cases peripheral nerve neurinomas can be excised with good results. Patients should be treated by a neurosurgeon with special expertise in peripheral nerve surgery. The patient should be thoroughly informed pre-operatively about any eventual new neurological deficits following surgery.

[Significance of distal motor latency after carpal tunnel operation]. / Zur Bedeutung der distalen motorischen Latenz nach Karpaltunneloperationen.

Motor distal latency (MDL) is one of the most important parameters in the electrodiagnosis of carpal tunnel syndrome (CTS). In a retrospective study of 1816 open surgical decompressions for CTS, a total of 612 postoperative motor nerve conduction measurements on 485 hands could be evaluated. In patients with good or satisfactory results after carpal tunnel release, an average improvement of MDL of 1.0 ms after 9-13 days, and of 2.2 ms after 1 year and longer was found. The individual motor nerve conduction improvement was in close correlation with the extent of preoperative prolongation of the MDL. Whereas relief of symptoms can be noted almost immediately, prolonged latencies often do not return to normal, even when the study is done a year later. Of the 10 patients with persisting symptoms, four had a new postoperative impairment of MDL, and also four had a marked improvement, whereas it remained unchanged in two. Patients with severe recurrent CTS presented in 11 out of 31 cases with an improved MDL from 0.3 ms to 3.0 ms in comparison to the initial preoperative evaluation; in 6 hands MDL was unchanged, further prolongation up to 2.0 ms was seen in 6 cases and marked worsening with new loss of motor response had to be noted in 8 hands at repeat electrodiagnosis. In 33 cases of postoperative reflex sympathetic dystrophy, an improvement of MDL from 0.3 ms to 3.3 ms (mean 1.7 ms) was observed in 22 hands and dissolution of a preexisting motor conduction block in three others, whereas two remained unchanged (without motor response) and an electrophysiological impairment was found only in six hands. Three of them presented with a further prolongation of MDL from 0.3 to 1.0 ms and a new loss of response was noted in the remaining three. In conclusion, postoperative motor nerve conduction studies may assess a favorable course following carpal tunnel release. However, they are often not helpful when surgical results are unsatisfactory, and indication for repeat surgical decompression should be based merely on clinical symptoms.

Islet cell antibodies in diabetes mellitus associated with a mitochondrial tRNA(Leu(UUR)) gene mutation.

An A3243G point mutation of the mitochondrial tRNA(Leu(UUR)) gene was detected in a Caucasian family with maternal diabetes mellitus and signs of mitochondrial dysfunction such as muscular hypotonia, encephalopathy, lactic acidosis, stroke-like episodes (MELAS), neurosensory hearing loss, cardial pre-excitation, and short stature. Low levels (10 JDF) of islet cell antibodies (ICA) in insulin-treated diabetes of the mother and impaired glucose tolerance with high levels of ICA (80 JDF) in her older son indicated that mitochondrial diabetes mellitus may involve beta cell damage. Furthermore, exocrine pancreas cell damage may also occur since the stroke-like episodes of this son were combined with pancreatitis. In all family members HLA types and plasma antioxidants were determined. Normal concentrations of hydro- and lipophilic antioxidants (including ubiquinol-10) were found.

[Intraoperative electrically evoked nerve action potentials in ulnar entrapment syndrome]. / Intraoperativ elektrisch evozierte Nervenaktionspotentiale beim Ulnarisrinnensydrom.

Many attempts have been made in the past to find predictive factors concerning patients operated on because of ulnar nerve entrapment at the elbow. The factors most frequently discussed in the literature are the patient's age, the importance of the preoperative neurological deficit, the duration of symptoms, accompanying diseases as diabetes mellitus or alcoholism and preoperative electrophysiological findings (EMG and conduction velocity measurements). With the exception of the electrophysiological findings, which uniformly are considered to be without predictive value, all other factors mentioned above are discussed controversly. In 1972 Kline and Nulsen [12] have shown, that intraoperatively evoked nerve action potentials across a traumatic nerve lesion can provide information about nerve regeneration. This information helps to choose the appropriate surgical procedure namely either neurolysis or neuroma resection and grafting. However there are no reports dealing with this method in nerve entrapment syndromes. We present the results of 17 patients with ulnar nerve entrapment at the elbow. They were operated on in our hospital between 1989 and 1992 by simple decompression or by anterior transposition of the nerve. In each of them we tried to record electrically evoked nerve action potentials intraoperatively and compared preoperative clinical findings with the potentials recorded. Our main interest was to find out, if the potentials have any predictive value regarding the clinical outcome. In 16 of 17 patients we were able to record a reproducable nerve action potential. Amplitudes varied between 3.4 and 140 uV. Conduction velocities of the fastest fibers ranged from 17 to 71 m/s, while potential duration varied between 1.3 to more than 8 ms.(ABSTRACT TRUNCATED AT 250 WORDS)