Maarten Moens

Brain-derived neurotrophic factor as a driving force behind neuroplasticity in neuropathic and central sensitization pain: a new therapeutic target?

Introduction: Central sensitization is a form of maladaptive neuroplasticity underlying many chronic pain disorders, including neuropathic pain, fibromyalgia, whiplash, headache, chronic pelvic pain syndrome and some forms of osteoarthritis, low back pain, epicondylitis, shoulder pain and cancer pain. Brain-derived neurotrophic factor (BDNF) is a driving force behind neuroplasticity, and it is therefore crucial for neural maintenance and repair. However, BDNF also contributes to sensitization of pain pathways, making it an interesting novel therapeutic target. Areas covered: An overview of BDNF’s sensitizing capacity at every level of the pain pathways is presented, including the peripheral nociceptors, dorsal root ganglia, spinal dorsal horn neurons, and brain descending inhibitory and facilitatory pathways. This is followed by the presentation of several potential therapeutic options, ranging from indirect influencing of BDNF levels (using exercise therapy, anti-inflammatory drugs, melatonin, repetitive transcranial magnetic stimulation) to more specific targeting of BDNF’s receptors and signaling pathways (blocking the proteinase-activated receptors 2–NK-κβ signaling pathway, administration of phencyclidine for antagonizing NMDA receptors, or blockade of the adenosine A2A receptor). Expert opinion: This section focuses on combining pharmacotherapy with multimodal rehabilitation for balancing the deleterious and therapeutic effects of BNDF treatment in chronic pain patients, as well as accounting for the complex and biopsychosocial nature of chronic pain.

Insulin-Like Growth Factor I Serum Levels Influence Ischemic Stroke Outcome

Background and Purpose— Insulin-like growth factor I (IGF-I) is neuroprotective in animal models of stroke. We investigated whether serum IGF-I levels in patients with acute ischemic stroke influence stroke severity and outcome. Methods— Concentrations of IGF-I and IGF binding protein 3 were measured in serum samples obtained within 6 hours after stroke onset from 255 patients who took part in the placebo arm of the United States and Canadian Lubeluzole in Acute Ischemic Stroke Study. Stroke severity was assessed with the National Institutes of Health Stroke Scale. Multivariate analysis was performed to assess the overall shift in modified Rankin Scale score and changes in the National Institutes of Health Stroke Scale score at 3 months. Survival curves were plotted using the Kaplan-Meier method, and the Cox proportional hazard model was used for multivariate analysis to investigate factors influencing survival. Results— After controlling for statistically relevant risk factors, subjects with high IGF-I levels or IGF-I/IGF binding protein 3 ratios had a better neurological and functional outcome at 3 months. Baseline stroke severity was not different between high and low IGF-I groups. In contrast to the low IGF-I group, neurological symptoms gradually improved from Day 3 in the high IGF-I group. Conclusions— Our results suggest that high serum IGF-I levels just after ischemic stroke onset are associated with neurological recovery and a better functional outcome.

Single Fraction Versus Fractionated Linac-Based Stereotactic Radiotherapy for Vestibular Schwannoma: A Single-Institution Experience

PURPOSE To evaluate and compare outcomes for patients with vestibular schwannoma (VS) treated in a single institution with linac-based stereotactic radiosurgery (SRS) or by fractionated stereotactic radiotherapy (SRT). METHODS AND MATERIALS One hundred and nineteen patients (SRS = 78, SRT = 41) were treated. For both SRS and SRT, beam shaping is performed by a mini-multileaf collimator. For SRS, a median single dose of 12.5 Gy (range, 11-14 Gy), prescribed to the 80% isodose line encompassing the target, was applied. Of the 42 SRT treatments, 32 treatments consisted of 10 fractions of 3-4 Gy, and 10 patients received 25 sessions of 2 Gy, prescribed to the 100% with the 95% isodose line encompassing the planning target volume. Mean largest tumor diameter was 16.6 mm in the SRS and 24.6 mm in the SRT group. Local tumor control, cranial nerve toxicity, and preservation of useful hearing were recorded. Any new treatment-induced cranial nerve neuropathy was scored as a complication. RESULTS Median follow-up was 62 months (range, 6-136 months), 5 patients progressed, resulting in an overall 5-year local tumor control of 95%. The overall 5-year facial nerve preservation probability was 88% and facial nerve neuropathy was statistically significantly higher after SRS, after prior surgery, for larger tumors, and in Koos Grade ≥3. The overall 5-year trigeminal nerve preservation probability was 96%, not significantly influenced by any of the risk factors. The overall 4-year probability of preservation of useful hearing (Gardner-Robertson score 1 or 2) was 68%, not significantly different between SRS or SRT (59% vs. 82%, p = 0.089, log rank). CONCLUSION Linac-based RT results in good local control and acceptable clinical outcome in small to medium-sized vestibular schwannomas (VSs). Radiosurgery for large VSs (Koos Grade ≥3) remains a challenge because of increased facial nerve neuropathy.

Prehospital Unassisted Assessment of Stroke Severity Using Telemedicine A Feasibility Study

Background and Purpose— We evaluated the feasibility and the reliability of remote stroke severity quantification in the prehospital setting using the Unassisted TeleStroke Scale (UTSS) via a telestroke ambulance system and a fourth-generation mobile network. Methods— The technical feasibility and the reliability of the UTSS were studied in healthy volunteers mimicking 41 stroke syndromes during ambulance transportation. Results— Except for 1 issue, high-quality telestroke assessment was feasible in all scenarios. The mean examination time for the UTSS was 3.1 minutes (SD, 0.4). The UTSS showed excellent intrarater and interrater variability (&rgr;=0.98 and 0.97; P<0.001), as well as excellent internal consistency and rater agreement. Adequate concurrent validity can be derived from the strong correlation between the UTSS and the National Institutes of Health Stroke Scale (&rgr;=0.90; P<0.001). Conclusions— Remote assessment of stroke severity in fast-moving ambulances using a system dedicated to prehospital telemedicine, 4G technology, and the UTSS is feasible and reliable.

Social determinants of sports participation revisited. The role of socialization and symbolic trajectories

Abstract This paper discusses the sociological debate of detraditionalization in the case of sports participation in Flanders. Sports participation remains to a great extent predictable by means of social characteristics. Traditional position-bound stratification mechanisms, based on age and gender identities, remain important determinants of sports participation behaviour. But more intentional socialization mechanisms such as the educational level, the formal social participation as well as the respondents’ media preferences and TV viewing habits, appear to be important in explaining sports participation.

Unassisted Assessment of Stroke Severity Using Telemedicine

Background and Purpose— Quantification of stroke severity through telemedicine consultation is challenging and relies on professional support at the patient’s bedside. We aimed to develop a novel scale for assessing stroke severity through telemedicine without assistance from a third party (Unassisted TeleStroke Scale [UTSS]). Methods— Stroke severity was assessed in 45 patients with suspicion of acute stroke by bedside examination using the National Institutes of Health Stroke Scale (NIHSS) and by teleconsultation using the UTSS. Scale reliability was evaluated by intrarater and interrater variability, internal consistency, and rater agreement. Concurrent and predictive validity were tested by relating the UTSS with the NIHSS and long-term outcome (modified Rankin Scale and mortality at 6 months). Clinimetric analysis of the UTSS was obtained via the Rasch model. Results— The mean examination time for the UTSS was 3.1 minutes (SD, 1.1) versus 8.5 minutes for the NIHSS (SD, 2.6; P<0.001). Both UTSS and NIHSS showed excellent intrarater variability (r=0.97 and 0.98; P<0.001) and interrater variability (r=0.96 and 0.98; P<0.001), as well as excellent internal consistency and rater agreement. The UTSS correlated strongly with the NIHSS and was identified as an independent predictor of stroke outcome in logistic regression analysis. Rasch analysis indicated that the UTSS represents a unidimensional scale of stroke severity. Conclusions— The UTSS is a rapid, reliable, and valid tool for unassisted assessment of stroke severity through telemedicine.

Posterior Fossa Syndrome After Cerebellar Stroke

Posterior fossa syndrome (PFS) due to vascular etiology is rare in children and adults. To the best of our knowledge, PFS due to cerebellar stroke has only been reported in patients who also underwent surgical treatment of the underlying vascular cause. We report longitudinal clinical, neurocognitive and neuroradiological findings in a 71-year-old right-handed patient who developed PFS following a right cerebellar haemorrhage that was not surgically evacuated. During follow-up, functional neuroimaging was conducted by means of quantified Tc-99m-ECD SPECT studies. After a 10-day period of akinetic mutism, the clinical picture developed into cerebellar cognitive affective syndrome (CCAS) with reversion to a previously learnt accent, consistent with neurogenic foreign accent syndrome (FAS). No psychometric evidence for dementia was found. Quantified Tc-99m-ECD SPECT studies consistently disclosed perfusional deficits in the anatomoclinically suspected but structurally intact bilateral prefrontal brain regions. Since no surgical treatment of the cerebellar haematoma was performed, this case report is presumably the first description of pure, “non-surgical vascular PFS”. In addition, reversion to a previously learnt accent which represents a subtype of FAS has never been reported after cerebellar damage. The combination of this unique constellation of poststroke neurobehavioural changes reflected on SPECT shows that the cerebellum is crucially implicated in the modulation of neurocognitive and affective processes. A decrease of excitatory impulses from the lesioned cerebellum to the structurally intact supratentorial network subserving cognitive, behavioural and affective processes constitutes the likely pathophysiological mechanism underlying PFS and CCAS in this patient.

Intravenous thrombolysis with recombinant tissue plasminogen activator in a stroke patient treated with apixaban

Apixaban is increasingly used in clinical practice (1), but data on the bleeding risk in patients treated with recombinant tissue plasminogen activator (rt-PA) while taking apixaban are nonexistent. A 74-year-old right-handed man presented with abrupt onset of global aphasia. He was known with a partial right hemianopsia secondary to a left occipital intracerebral hemorrhage five-years earlier and with paroxysmal nonvalvular atrial fibrillation treated with apixaban 5 mg bid. The National Institutes of Health Stroke Scale (NIHSS) score was 8. Noncontrast computed tomography (CT) of the brain showed no signs of acute intracranial pathology. Perfusion-CT revealed hypoperfusion in the territory of the left middle cerebral artery (Fig. 1a). An ostial stenosis of the left internal carotid artery was diagnosed on CT angiography (Fig. 1b). After informed consent by proxy, i.v. rt-PA therapy (0·9 mg/kg; total dose 81 mg) was administered at 4·5 h after symptom onset and 8·5 h after apixaban intake. Platelet count, prothrombin time, activated partial thromboplastin time, and fibrinogen levels were normal, as was creatinine clearance. The patient experienced an excellent recovery (NIHSS score 1) without signs of new infarction or intracranial hemorrhage on repeat CT. As apixaban is commonly used in patients with elevated stroke risk (1), therapeutic decision-making with regard to thrombolytic therapy may not uncommonly pose problems in the near future. Our case report illustrates that further study on the safety of rt-PA in this patient population is justified. Ann De Smedt*, Melissa Cambron, Koenraad Nieboer, Maarten Moens, Robbert-Jan Van Hooff, Laetitia Yperzeele, Kristin Jochmans, Jacques De Keyser, and Raf Brouns

Feasibility of cerebral magnetic resonance imaging in patients with externalised spinal cord stimulator

OBJECT Spinal cord stimulation (SCS) is a well-known treatment option for intractable neuropathic pain after spinal surgery, but its pathophysiological mechanisms are poorly stated. The goal of this study is to analyse the feasibility of using brain MRI, functional MRI (fMRI) and Magnetic Resonance Spectroscopy (MRS) as tools to analyse these mechanisms in patients with externalised neurostimulators during trial period. METHODS The authors conducted in an in vitro and in vivo study analysing safety issues when performing brain MRI, fMRI and MRS investigations in human subjects with externalised SCS. Temperature measurements in vitro were performed simulating SCS during MRI sequences using head transmit-receive coils in 1.5 and 3 T MRI systems. 40 Patients with externalised SCS were included in the in vivo study. 20 patients underwent brain MRI, fMRI and another 20 patients underwent brain MRI and MRS. RESULTS A maximal temperature increase of 0.2°C was measured and neither electrode displacements nor hardware failures were observed. None of the patients undergoing the MRS sequences at the 1.5 or 3 T MRI scanners described any discomfort or unusual sensations. CONCLUSION We can conclude that brain MRI, fMRI and MRS studies performed in patients with externalised SCS can be safely executed.

Spinal cord stimulation modulates cerebral neurobiology: A proton magnetic resonance spectroscopy study

IntroductionAlthough spinal cord stimulation (SCS) is a widely used treatment for chronic neuropathic pain secondary to spinal surgery, little is known about the underlying physiological mechanisms.MethodsThe primary aim of this study is to investigate the neural substrate underlying short-term SCS by means of 1H MR spectroscopy with short echo time, in 20 patients with failed back surgery syndrome.ResultsMarked increase of γ-aminobutyric acid (GABA) and decrease in glucose in the ipsilateral thalamus were found between baseline situation without SCS and after 9′ of SCS, indicating the key role of the ipsilateral thalamus as a mediator of chronic neuropathic pain. In addition, this study also showed a progressive decrease in glucose in the ipsilateral thalamus over time, which is in line with the findings of previous studies reporting deactivation in the ipsilateral thalamic region.ConclusionsThe observation of GABA increase and glucose decrease over time in the ipsilateral thalamus may be the causal mechanism of the pain relief due to SCS or an epiphenomenon.