Implementation of Transforaminal Endoscopic Lumbar Sequestrectomy in a German University Hospital Setting: A Long and Rocky Road.

OBJECTIVE: Microsurgical diskectomy/sequestrectomy is the standard procedure for the surgical treatment of lumbar disk herniations. The transforaminal endoscopic sequestrectomy technique is a minimally invasive alternative with potential advantages such as minimal blood loss and tissue damage, as well as early mobilization of the patient. We report the implementation of this technique in a German university hospital setting. METHODS: One single surgeon performed transforaminal endoscopic sequestrectomy from February 2013 to July 2016 for lumbar disk herniation in 44 patients. Demographic as well as perioperative, clinical, and radiologic data were analyzed from electronic records. Furthermore, we investigated complications, intraoperative change of the procedure to microsurgery, and reoperations. The postoperative course was analyzed using the Macnab criteria, supplemented by a questionnaire for follow-up. Pre- and postoperative magnetic resonance imaging volumetric analyses were performed to assess the radiologic efficacy of the technique. RESULTS: Our study population had a median age of 52 years. The median follow-up was 15 months, and the median length of hospital stay was 4 days. Median duration of surgery was 100 minutes with a median blood loss of 50 mL. Surgery was most commonly performed at the L4-L5 level (63%) and in caudally migrated disk herniations (44%). In six patients, surgery was performed for recurrent disk herniations. The procedure had to be changed to conventional microsurgery in four patients. We observed no major complications. Minor complications occurred in six patients, and in four patients a reoperation was performed. Furthermore, a significantly lower Oswestry Disability Index score (p = 0.03), a lower Short Form 8 Health Survey (SF-8) score (p = 0.001), a lower visual analog scale (VAS) lower back pain score (p = 0.03) and VAS leg pain score (p = 0.0008) at the 12-month follow-up were observed in comparison with the preoperative examination. In MRI volumetry, we detected a median postoperative volume reduction of the disk herniation of 57.1% (p = 0.02). CONCLUSIONS: The transforaminal endoscopic sequestrectomy can be safely implemented in a university hospital setting in selected patients with primary and recurrent lumbar disk herniations, and it leads to good clinical and radiologic results. However, learning curve, caseload, and residents' microsurgical training requirements clearly affect the implementation process.

In vitro examination of the thrombolytic efficacy of tenecteplase and therapeutic ultrasound compared to rt-PA.

BACKGROUND: Optimizing thrombolytic therapy is vital for improving stroke outcomes. We aimed to develop standardized thrombolysis conditions to evaluate the efficacy of tenecteplase (TNK) compared to the current gold standard rt-PA (alteplase), with and without additional ultrasound treatment. We also wanted to introduce a new analytical approach to quantify fibrin fiber density in transmission electron microscopy (TEM). METHODS: In vitro clots that are similar to ex vivo clots concerning their histological condition and their durability were generated from whole blood. For five treatment groups we compared relative clot weight loss (each n = 60) and fibrin fiber density in TEM (each n = 5). The control group (A) was treated only with plasma. Two groups were designated for each rt-PA (B + C) and TNK (D + E). Groups C and E were additionally treated with ultrasound. Dosages were 50 µg/ml for rt-PA and 30 µg/ml for TNK. Results were evaluated by using analyses of variance (ANOVA) and post-hoc t-tests. RESULTS: Weight loss was increased significantly for all groups compared to the control group. Both TNK groups showed significantly increased weight loss compared to their counterpart rt-PA group (p ≤ 0.001). For TEM only group D showed significantly decreased fibrin fiber density (p < 0.05) compared to both rt-PA groups. Ultrasound did not significantly increase dissolution of clots with either method (best p = 0.16). CONCLUSIONS: Tenecteplase dissolved clots more effectively than rt-PA with and without ultrasound. A higher sample size could provide more convincing results for TEM.

Nigrosome 1 visibility at susceptibility weighted 7T MRI-A dependable diagnostic marker for Parkinson's disease or merely an inconsistent, age-dependent imaging finding?

BACKGROUND: Visualisation of nigrosome 1, a substructure of the healthy substantia nigra, was restricted in susceptibility weighted MR imaging in almost all patients with Parkinson's disease studied so far. The purpose of this study was to determine the degree of visibility of this substructure in subjects without Parkinson's disease and to examine the potential link between increasing brain iron accumulation with age and its detectability. METHODS: In 46 subjects (21 women, 25 men; 19 to 75 y; mean age: 44.5; SD: 15.6) examined with susceptibility weighted MR imaging at 7T visibility of nigrosome 1 was rated and classified. We assessed differences related to age and to signal intensities in the substantia nigra, red nucleus and putamen as correlates of the individual iron concentration. RESULTS: In 93% nigrosome 1was at least unilaterally clearly present. In 24% at least one-sided limited visibility was observed. Using predefined classification criteria the specificity of the visibility across all age groups reached approximately 94%. We found no correlation with increasing iron concentrations with age. CONCLUSION: Aging with a related increase in iron concentration probably does not affect the visibility of nigrosome 1 at 7T SWI MRI. Our results support the role of this feature as a future differential diagnostic tool but further large-scale prospective studies are needed to better define the extent of a "limited visibility" to which an individual can be considered healthy.

Tumor response assessment: comparison between unstructured free text reporting in routine clinical workflow and computer-aided evaluation based on RECIST 1.1 criteria.

PURPOSE: Standardized computer-aided tumor response assessment is common in clinical trials. In contrast, unstructured free text reporting (UFTR) is common in daily routine. Therefore, this study aimed to discern and quantify differences between UFTR and computer-aided standardized tumor response evaluation based on RECIST 1.1 criteria (RECIST), serving as gold standard, in clinical workflow. METHODS: One-hundred consecutive patients with cancer eligible for RECIST 1.1 evaluation, who received five follow-up CTs of the trunk, were retrospectively included. All UFTRs were assigned to RECIST response categories [complete response, partial response (PR), stable disease (SD), progressive disease (PD)]. All CTs were re-evaluated using dedicated software (mint lesion™) applying RECIST 1.1. The accordance in tumor response ratings was analyzed using Cohen's kappa. RESULTS: At the first follow-up, 47 cases were rated differently with an SD underrepresentation and a PR and PD overrepresentation in UFTR. In the subsequent follow-ups, categorical differences were seen in 38, 44, 37, and 44%. Accordance between UFTR and RECIST was fair to moderate (Cohen's kappa: 0.356, 0.477, 0.390, 0.475, 0.376; always p < 0.001). Differences were mainly caused by the rating of even small tumor burden changes as PD or PR in UFTR or by comparison to the most recent prior CT scan in UFTR instead of comparison to nadir or baseline. CONCLUSIONS: Significant differences in tumor response ratings were detected comparing UFTR and computer-aided standardized evaluation based on RECIST 1.1. Thus, standardized reporting should be implemented in daily routine workflow.

Diagnostic impact of integrated 18F-FDG PET/MRI in cerebral staging of patients with non-small cell lung cancer.

Background Integrated positron emission tomography/magnetic resonance imaging (PET/MRI) systems are increasingly being available and used for staging examinations. Brain metastases (BM) are frequent in patients with non-small cell lung cancer (NSCLC) and decisive for treatment strategy. Purpose To assess the diagnostic value of integrated 18F-2-fluoro-2-deoxy-D glucose (18F-FDG) PET/MRI in initial staging in patients with NSCLC for BM in comparison to MRI alone. Material and Methods Eighty-three patients were prospectively enrolled for an integrated 18F-FDG PET/MRI examination. The 3 T MRI protocol included a fluid-attenuated inversion-recovery sequence (FLAIR) and a contrast-enhanced three-dimensional magnetization prepared rapid acquisition GRE sequence (MPRAGE). Two neuroradiologists evaluated the datasets in consensus regarding: (i) present lesions; (ii) size of lesions; and (iii) number of lesions detected in MRI alone, compared to the PET component when reading the 18F-FDG PET/MRI. Results Based on MRI alone, BM were detected in 15 out of the 83 patients, comprising a total of 39 metastases. Based on PET alone, six patients out of the 83 patients were rated positive for metastatic disease, revealing a total of 15 metastases. PET detected no additional BM. The size of the BM correlated positively with sensitivity of detection in PET. Conclusion The sensitivity of PET in detection of BM depends on their size. 18F-FDG PET/MRI does not lead to an improvement in diagnostic accuracy in cerebral staging of NSCLC patients, as MRI alone remains the gold standard.

Can we now dispense with DSA in the evaluation of aneurysm occlusion even in the most crucial first follow-up after endovascular treatment?

OBJECTIVES: Catheter angiography (DSA) as gold standard for the evaluation of aneurysmal occlusion after coiling has now been largely replaced by MRI or CTA in long term observations. However, the first year after treatment is crucial because most recurrences occur in this time. Until now no guidelines exist concerning the imaging modality to adopt in this period. Aim of the study was to determine whether DSA could also be omitted in the first follow-up examination after coiling due to MRI results. PATIENTS AND METHODS: 489 consecutive half-year follow-up examinations consisting of DSA, CE-MRA and TOF-MRA at 1.5 or 3T were reviewed retrospectively. Visualization of residual or recurrent aneurysms in both MRA-techniques was compared to DSA by two experienced readers. RESULTS: Remnants/recurrences could be visualized in at least one of the three techniques in 190 (38.9%) aneurysms. Remnants/recurrences requiring retreatment (n=52) were detectable with at least one of the two MRI-techniques. In three cases (0.6%) remnants/recurrences were only visible on DSA but neither on CE-MRA nor on TOF-MRA. However, they were small (<2mm) and therapy concept did not change. In one case (0.2%) they were only visible on the CE-MRA and TOF-MRA but not on the DSA, in five cases (1%) visible on DSA and TOF-MRA but not on the CE-MRA and in four cases (0.8%) not visible on the TOF-MRA but on both of the other imaging modalities. CONCLUSION: The combination of CE-MRA und TOF-MRA is also an appropriate alternative to DSA concerning the evaluation of residual or recurrent aneurysms in the crucial first follow-up.

Chudley-McCullough Syndrome: Variable Clinical Picture in Twins with a Novel GPSM2 Mutation.

Chudley-McCullough syndrome (CMS) is a rare autosomal recessive disorder characterized by sensorineural deafness, agenesis of the corpus callosum, frontal polymicrogyria, interhemispheric cyst, and ventricular enlargement. CMS is caused by mutations in the GPSM2 gene, but until now no more than eight different mutations are on record. We describe two dizygotic twins with a novel homozygous loss-of-function mutation (c.1093C > T; p.Arg365*). While one child developed hydrocephalus-prompting shunt implantation immediately after birth, the other sibling did not. The combination of sensorineural hearing loss and partial agenesis of the corpus callosum is a highly recognizable clinico-radiological entity that should prompt mutational analysis of the GPSM2 gene.

Diagnosing moyamoya syndrome using ultrasound - a case report.

BACKGROUND: Moyamoya syndrome is a vasculopathy characterised by progressive occlusion of the cerebral arteries resulting in the development of abnormal collateral circulation. To diagnose this syndrome, imaging of the cerebral arteries is required including CT- or MR-angiography and conventional angiography. We present a case of moyamoya disease with typical findings detected in the sonography. The diagnosis was suspected after reviewing the initial ultrasound images of the cerebral arteries with evidence for obliterated intracranial arteries and the detection of an existing collateral circulation network. CASE PRESENTATION: A 62 years old male patient presented in the hospital's emergency department with symptoms indicating a subacute cerebrovascular event. Immediate sonographic studies showed a right-sided pulsatile Doppler-signal in the common and internal carotid arteries, suggestive of distal stenoses. In addition, the transcranial examination indicated obliteration of both middle cerebral arteries. Numerous arterial vessels suggestive of leptomeningeal collateral arteries revealed a strong arterial leptomeningeal flow. At this stage of the diagnostic work-up, the collateral circulation network, characteristic of moyamoya disease, was indicated by sonography. Moyamoya syndrome was verified by conventional angiography. The aetiological work remained empty, so the diagnosis of moyamoya disease was established. CONCLUSION: Our case report indicates that sonography can be a useful tool for detecting the vaculopathy in moyamoya syndrome. In case routine procedures, such as the CT- or MR-angiography, with evidence for obliterated intracerebral arteries, ultrasound studies might provide important information regarding an existing collateral network in the scope of a moyamoya syndrome.

Neural underpinnings of nocebo hyperalgesia in visceral pain: A fMRI study in healthy volunteers.

Despite the clinical relevance of nocebo effects, few studies have addressed their underlying neural mechanisms in clinically-relevant pain models. We aimed to address the contribution of nocebo effects and their underlying neural circuitry to central pain amplification in visceral pain, as it may develop over repeated painful experiences due to negative pain-related expectations. Healthy volunteers received verbal suggestions of pain sensitization (nocebo group, N=28) or neutral instructions (control group, N=16). fMRI was used to investigate changes in neural responses during cued pain anticipation and painful rectal distensions delivered in successive fMRI sessions. Pain intensity was rated trial-by-trial, and expected pain intensity, state anxiety and tension were assessed prior to each session. Behavioral analyses demonstrated significantly greater increases in both expected and perceived pain in the nocebo group. The fMRI analysis performed on nocebo-responders only (N=14) revealed that these behavioral changes were associated with increased activation within the secondary somatosensory cortex and amygdala during pain anticipation and within the thalamus, insula and amygdala during painful stimulation when compared to controls. A subsequent psycho-physiological interaction analysis of the pain phase showed increased functional connectivity between the anterior insula, which was set-up as seed region based on group results, and midcingulate cortex as a function of negative expectations. These findings support that negative pain-related expectations can play a crucial role in pain amplification of visceral pain, which is mediated, at least in part, by a neural up-regulation of pain-associated areas and their connectivity. These findings may have implications for the pathophysiology and treatment of chronic abdominal pain.

Value of DSA in the diagnostic workup of pulsatile tinnitus.

OBJECTIVES: Pulsatile tinnitus (PT) is a rare complaint, but can be a symptom of life-threatening disease. It is often caused by vascular pathologies, e.g. dural arteriovenous fistula (dAVF), arteriovenous malformation (AVM) or vascularized tumors. The current diagnostic pathway includes clinical examination, cranial MRI and additional DSA. The aim of this study was to evaluate the diagnostic impact of DSA in the diagnostic workup of patients with PT in comparison to MRI alone. METHODS: Retrospectively, 54 consecutive patients with pulsatile tinnitus were evaluated. All patients had a diagnostic workup including cranial MRI and DSA. MRI examinations were blinded to the results of DSA and retrospectively analyzed in consensus by two experienced neuroradiologists. The MR-examinations were evaluated for each performed sequence separately: time-of-flight-angiography, ce-MRA, T2, ce-T1-sequence and ce-T1-sequence with fat saturation. RESULTS: 37 of the 54 patients revealed a pathology explaining PT on MRI, which was detected by the readers in 100% and proofed by means of DSA. 24 dAVF, four paraganglioma, two AVM and seven more pathologies were described. All patients without pathology on MRI did also not show any pathology in DSA. CONCLUSIONS: MR imaging is sufficient to exclude pathology in patients with pulsatile tinnitus.

Intracranial hemorrhage detection over time using susceptibility-weighted magnetic resonance imaging.

BACKGROUND: The reliable detection of intracranial hemorrhages is important, but just 1 year after the hemorrhage onset it might be missed using T2-weighted spin-echo and gradient-echo sequences. Susceptibility-weighted imaging (SWI) is a new magnetic resonance imaging sequence that is extremely sensitive in hemorrhage detection and that might improve the detection of hemorrhages over time. PURPOSE: To investigate whether the detectability of intracranial blood and its degradation products is independent of the time span after intracranial hemorrhage using SWI. MATERIAL AND METHODS: Sixty-six consecutive patients (28 men, 38 women) with definitely known time point of intracranial hemorrhage and available SWI sequence (1.5 or 3 T) were analyzed retrospectively. Twenty-one patients had a SWI follow-up. All SWI images were assessed by two radiologists in consensus regarding hemorrhage visibility using a 5-point scale. Statistical analysis was performed using Spearman's correlation test. RESULTS: Median time interval between hemorrhage and first available SWI measurement was 819 days (range, 0 days to 13.2 years). Nine of 66 patients had an isolated subarachnoid hemorrhage (iSAH) and were therefore analyzed separately. In eight of these nine patients the hemorrhage could clearly be detected, the remaining one had minor iSAH. Spearman analysis showed no significant correlation between time span and visibility (P = 0.660). In the remaining 57 patients (no iSAH) the hemorrhage was always visible achieving at least 3/5 points on the 5-point scale, and Spearman's analysis revealed only a weak correlation between time span and visibility (r = 0.493, P < 0.001). CONCLUSION: The detectability of blood and its degradation products using SWI is reliably possible over a long period after intracranial hemorrhage.

Diagnostic value of 3D fluid attenuated inversion recovery sequence in multiple sclerosis.

BACKGROUND: Magnetic resonance imaging (MRI) is an indispensable tool in the diagnostic work-up of multiple sclerosis (MS). To date, guidelines suggest MRI protocols containing axial dual-echo, unenhanced and post-contrast T1-weighted sequences. Especially the usage of dual-echo sequences has markedly improved the ability of MRI to detect cortical and infratentorial lesions. Newer 3D FLAIR sequences are supposed to provide even more positive imaging features such as improved detection of white matter lesions and a better resolution due to smaller slice thickness. PURPOSE: To evaluate the diagnostic impact of 3D FLAIR sequences in comparison to conventional T2 and PD sequences. MATERIAL AND METHODS: Examinations of 20 MS patients (10 women, 10 men) were reviewed retrospectively. All patients received MRI standard protocol containing PD and T2 sequences and a mid-sagittal T2 sequence. Additionally an isotropic 3D FLAIR sequence was performed. Whole-brain lesion load and number of lesions in juxtacortical, infratentorial, and midcallosal localizations were assessed by two observers independently and compared. RESULTS: Whole lesion load and the count of detectable lesions at the 3D FLAIR sequence were significantly higher in the juxtacortical and infratentorial regions compared to the PD/T2 sequence. Detection rate of midcallosal lesions did not differ significantly in sagittal T2 and 3D FLAIR sequence. CONCLUSION: 3D FLAIR sequences can improve the detection of brain lesions in patients with MS and are even more sensitive in depicting lesions in cortical and infratentorial locations than current dual-echo sequences. The sequence can replace both PD/T2 sequences and mid-sagittal T2 sequences of the corpus callosum.

Learning pain-related fear: neural mechanisms mediating rapid differential conditioning, extinction and reinstatement processes in human visceral pain.

BACKGROUND AND AIMS: There exists converging evidence to support a role of pain-related fear in the pathophysiology and treatment of chronic pain conditions. Pain-related fear is shaped by associative learning and memory processes, which remain poorly characterized especially in the context of abdominal pain such as in irritable bowel syndrome (IBS). Therefore, using event-related functional magnetic resonance imaging (fMRI), we assessed the neural mechanisms mediating the formation, extinction and reinstatement of abdominal pain-related fear in healthy humans. Employing painful rectal distensions as clinically-relevant unconditioned stimuli (US), in this fear conditioning study we tested if differential excitatory and inhibitory learning is evocable after very few CS-US learning trials ("rapid conditioning"), and explored the underlying neural substrates of these learning and memory processes. METHODS: In N=24 healthy men and women, "rapid" fear acquisition was accomplished by pairing visual conditioned stimuli (CS(+)) with painful rectal distensions as unconditioned stimuli (US), while different visual stimuli (CS(-)) were presented without US (differential delay conditioning with five CS(+) and five CS(-) presentations and a 80% reinforcement ratio). During extinction, all CS were presented without US. Subsequently, a reinstatement procedure was implemented, defined as the retrieval of an extinguished memory after unexpected and unpaired exposure to the US, followed by CS presentations. For each phase, changes in perceived CS-US contingency and CS unpleasantness were assessed with visual analogue scales and compared with analyses of variance. fMRI data were analyzed using whole-brain analyses (at p<.001 uncorrected) and in regions-of-interest analyses with familywise error correction of alpha (pFWE<.05). Differential neural activation in response to the CS during each experimental phase (i.e., CS(+)>CS(-); CS(+)

Neural mechanisms mediating positive and negative treatment expectations in visceral pain: a functional magnetic resonance imaging study on placebo and nocebo effects in healthy volunteers.

To elucidate placebo and nocebo effects in visceral pain, we conducted a functional magnetic resonance imaging (fMRI) study to analyze effects of positive and negative treatment expectations in a rectal pain model. In 36 healthy volunteers, painful rectal distensions were delivered after intravenous application of an inert substance combined with either positive instructions of pain relief (placebo group) or negative instructions of pain increase (nocebo group), each compared to neutral instructions. Neural activation during cued-pain anticipation and pain was analyzed along with expected and perceived pain intensity. Expected and perceived pain intensity were significantly increased in the nocebo group and significantly decreased in the placebo group. In the placebo group, positive expectations significantly reduced activation of the somatosensory cortex during anticipation and of the insula, somatosensory cortex, and amygdala during pain delivery when compared to neutral expectations. Within the nocebo group, negative expectations led to significantly increased insula activation during painful stimulation. Direct group contrasts during expectation modulation revealed significantly increased distension-induced activation within the somatosensory cortex in the nocebo group. In conclusion, the experience and neural processing of visceral pain can be increased or decreased by drug-specific expectations. This first brain imaging study on nocebo effects in visceral pain has implications for the pathophysiology and treatment of patients with chronic abdominal complaints such as irritable bowel syndrome.

Isolated cerebral susceptibility artefacts in patients with malignant melanoma: metastasis or not?

OBJECTIVE: While staging patients with malignant melanoma, cerebral susceptibility artefacts on T2*-weighted/susceptibility-weighted imaging (SWI) sequences without a correlate on contrast-enhanced T1-weighted images can be confusing. Without intravenous contrast enhancement, cavernomas, microhaemorrhages and melanin-containing metastases represent possible differential diagnoses for these findings. The purpose of this study was to find out, how often such lesions correspond to metastases. METHODS: Brain MR images (1.5 T) of 408 patients with malignant melanoma but without cerebral metastases in the initial staging by MRI were reviewed retrospectively. Eighteen patients (5 female, 13 male) with malignant melanoma and signal intensity loss on T2*/SWI were included in our study. The average observation period was 19.6 months (6-46 months, 2006-2009). RESULTS: In each of these 18 patients between one and seven hypointense lesions on T2*/SWI were found. None of these lesions developed into metastasis. CONCLUSION: Focal areas of susceptibility artefacts in the brain parenchyma without corresponding abnormalities in contrast-enhanced T1 weighted images are unlikely to represent brain metastases. KEY POINTS: • In melanoma patients early diagnosis of metastatic brain lesions is mandatory. • Melanin content and haemorrhage are potential reasons for MRI characteristics of melanoma metastases. • Susceptibility-weighted MRI visualises melanin and blood products. • Isolated cerebral susceptibility artefacts do not convert into melanoma metastases. • SWI/T2* sequences cannot replace Gd-enhanced sequences.

Fear conditioning in an abdominal pain model: neural responses during associative learning and extinction in healthy subjects.

Fear conditioning is relevant for elucidating the pathophysiology of anxiety, but may also be useful in the context of chronic pain syndromes which often overlap with anxiety. Thus far, no fear conditioning studies have employed aversive visceral stimuli from the lower gastrointestinal tract. Therefore, we implemented a fear conditioning paradigm to analyze the conditioned response to rectal pain stimuli using fMRI during associative learning, extinction and reinstatement. In N = 21 healthy humans, visual conditioned stimuli (CS(+)) were paired with painful rectal distensions as unconditioned stimuli (US), while different visual stimuli (CS(-)) were presented without US. During extinction, all CSs were presented without US, whereas during reinstatement, a single, unpaired US was presented. In region-of-interest analyses, conditioned anticipatory neural activation was assessed along with perceived CS-US contingency and CS unpleasantness. Fear conditioning resulted in significant contingency awareness and valence change, i.e., learned unpleasantness of a previously neutral stimulus. This was paralleled by anticipatory activation of the anterior cingulate cortex, the somatosensory cortex and precuneus (all during early acquisition) and the amygdala (late acquisition) in response to the CS(+). During extinction, anticipatory activation of the dorsolateral prefrontal cortex to the CS(-) was observed. In the reinstatement phase, a tendency for parahippocampal activation was found. Fear conditioning with rectal pain stimuli is feasible and leads to learned unpleasantness of previously neutral stimuli. Within the brain, conditioned anticipatory activations are seen in core areas of the central fear network including the amygdala and the anterior cingulate cortex. During extinction, conditioned responses quickly disappear, and learning of new predictive cue properties is paralleled by prefrontal activation. A tendency for parahippocampal activation during reinstatement could indicate a reactivation of the old memory trace. Together, these findings contribute to our understanding of aversive visceral learning and memory processes relevant to the pathophysiology of chronic abdominal pain.