Limitations of prone positioning in patients with aneurysmal subarachnoid hemorrhage and concomitant respiratory failure.

OBJECTIVE: Prone positioning (PP) is an established treatment modality for respiratory failure. After aneurysmal subarachnoid hemorrhage (aSAH), PP is rarely performed considering the risk of intracranial hypertension. The aim of this study was to analyze the effects of PP on intracranial pressure (ICP), cerebral perfusion pressure (CPP) and cerebral oxygenation following aSAH. PATIENTS AND METHODS: Demographic and clinical data of aSAH patients admitted over a 6-year period and treated with PP due to respiratory insufficiency were retrospectively analyzed. ICP, CPP, brain tissue oxygenation (pBrO2), respiratory parameters and ventilator settings were analyzed before and during PP. RESULTS: Thirty patients receiving invasive multimodal neuromonitoring were included. Overall, 97 PP sessions were performed. Mean arterial oxygenation and pBrO2 increased significantly during PP. We found a significant increase in median ICP compared to the baseline level in supine position. No significant changes in CPP were observed. Five PP sessions had to be terminated early due to medically refractory ICP-crisis. The affected patients were younger (p = 0.02) with significantly higher baseline ICP values (p = 0.009). Baseline ICP correlates significantly (p < 0.001) with ICP 1 h (R: 0.57) and 4 h (R: 0.55) after onset of PP. CONCLUSION: PP in aSAH patients with respiratory insufficiency is an effective therapeutic option improving arterial and global cerebral oxygenation without compromising CPP. The significant increase in ICP was moderate in most sessions. However, as some patients experience intolerable ICP crises during PP, continuous ICP-Monitoring is considered mandatory. Patients with elevated baseline ICP and reduced intracranial compliance should not be considered for PP.

Volatile Sedation With Isoflurane in Neurocritical Care Patients After Poor-grade Aneurysmal Subarachnoid Hemorrhage.

OBJECTIVE: Volatile sedation after aneurysmal subarachnoid hemorrhage (aSAH) promises several advantages, but there are still concerns regarding intracranial hypertension due to vasodilatory effects. We prospectively analyzed cerebral parameters during the switch from intravenous to volatile sedation with isoflurane in patients with poor-grade (World Federation of Neurosurgical Societies grade 4-5) aSAH. METHODS: Eleven patients were included in this prospective observational study. Between day 3 and 5 after admission, intravenous sedation was switched to isoflurane using the Sedaconda Anesthetic Conserving Device (Sedana Medical, Danderyd, Sweden). Intracranial pressure (ICP), cerebral perfusion pressure (CPP), brain tissue oxygenation (PBrO2), cerebral mean flow velocities (MFVs; transcranial Doppler ultrasound) and regional cerebral oxygen saturation (rSO2, near-infrared spectroscopy monitoring), as well as cardiopulmonary parameters were assessed before and after the sedation switch (-12 to +12 hours). Additionally, perfusion computed tomography data during intravenous and volatile sedation were analyzed retrospectively for changes in cerebral blood flow. RESULTS: There were no significant changes in mean ICP, CPP, and PBrO2 after the sedation switch to isoflurane. Mean rSO2 showed a non-significant trend towards higher values, and mean MFV in the middle cerebral arteries increased significantly after the initiation of volatile sedation. Isoflurane sedation resulted in a significantly increased norepinephrine administration. Despite an increase in mean inspiratory pressure, we observed a significant increase in mean partial arterial pressure of carbon dioxide. CONCLUSIONS: Isoflurane sedation does not compromise ICP or cerebral oxygenation in poor-grade aSAH patients, but the significant depression of CPP could limit the use of volatiles in case of hemodynamic instability or high vasopressor demand.

Analysis of Angiographic Treatment Response to Intra-Arterial Nimodipine Bolus Injection in Patients with Medically Refractory Cerebral Vasospasm After Spontaneous Subarachnoid Hemorrhage.

BACKGROUND: Intra-arterial nimodipine (IAN) injections are performed in refractory delayed cerebral ischemia (DCI) related to cerebral vasospasm (CVS) after spontaneous subarachnoid hemorrhage (sSAH), but the clinical benefits are inconclusive and angiographic treatment failure is observed. We analyzed angiographic IAN response in a detailed vessel-specific manner and examined the impact of poor angiographic response on the further clinical course. METHODS: Clinical data were retrospectively assessed in patients with spontaneous subarachnoid hemorrhage with symptomatic CVS receiving IAN bolus treatment. Clinical and angiographic predictors for poor angiographic response, DCI-related infarction, and unfavorable outcome were analyzed. RESULTS: Eighty-nine patients were included and 356 treated vessel segments, mainly located in the anterior circulation (93%), were analyzed. Angiographic response was good in 77% of the treated segments. Older age, poor World Federation of Neurosurgical Societies (WFNS) grade 4-5 and early onset of CVS were independently associated with poor angiographic response. The factors short-segment, distal, and bilateral CVS as well as treatment of multiple vessel segments, WFNS grade 4-5, and early onset of CVS were significantly associated with an increased risk of DCI-related infarction. Clinical outcome was significantly influenced by poor WFNS grade and early onset of CVS, whereas poor angiographic response was not related to DCI-related infarction or unfavorable outcome. CONCLUSIONS: The risk of angiographic treatment failure is significantly increased in older patients and those with poor WFNS grade as in cases of early-onset CVS. Although the extent of angiographic CVS significantly affected the development of DCI-related infarction, poor angiographic response had no impact on cerebral infarction and clinical outcome.

Effects of post-interventional antiplatelet therapy on angiographic vasospasm, delayed cerebral ischemia, and clinical outcome after aneurysmal subarachnoid hemorrhage: a single-center experience.

Platelet activation has been postulated to be involved in the pathogenesis of delayed cerebral ischemia (DCI) and cerebral vasospasm (CVS) after aneurysmal subarachnoid hemorrhage (aSAH). The aim of this study was to investigate potentially beneficial effects of antiplatelet therapy (APT) on angiographic CVS, DCI-related infarction and functional outcome in endovascularly treated aSAH patients. Retrospective single-center analysis of aSAH patients treated by endovascular aneurysm obliteration. Based on the post-interventional medical regime, patients were assigned to either an APT group or a control group not receiving APT. A subgroup analysis separately investigated those APT patients with aspirin monotherapy (MAPT) and those receiving dual treatment (aspirin plus clopidogrel, DAPT). Clinical and radiological characteristics were compared between groups. Possible predictors for angiographic CVS, DCI-related infarction, and an unfavorable functional outcome (modified Rankin scale ≥ 3) were analyzed. Of 160 patients, 85 (53%) had received APT (n = 29 MAPT, n = 56 DAPT). APT was independently associated with a lower incidence of an unfavorable functional outcome (OR 0.40 [0.19-0.87], P = 0.021) after 3 months. APT did not reduce the incidence of angiographic CVS or DCI-related infarction. The pattern of angiographic CVS or DCI-related infarction as well as the rate of intracranial hemorrhage did not differ between groups. However, the lesion volume of DCI-related infarctions was significantly reduced in the DAPT subgroup (P = 0.011). Post-interventional APT in endovascularly treated aSAH patients is associated with better functional outcome at 3 months. The beneficial effect of APT might be mediated by reduction of the size of DCI-related infarctions.

Routine use of perfusion computed tomography for the detection of delayed cerebral ischemia in unconscious patients after aneurysmal subarachnoid hemorrhage.

BACKGROUND: Delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH) is difficult to diagnose in unconscious patients, but it is essential for the prognosis. We analyzed the diagnostic value of routinely performed perfusion computed tomography (rPCT) to detect DCI-related hypoperfusion in this subgroup of patients. METHODS: Retrospective analysis of unconscious aSAH patients who underwent rPCT according to a predefined protocol. We exclusively analyzed PCT examinations in patients who were clinically and functionally asymptomatic with regard to transcranial Doppler ultrasound (TCD) and invasive neuromonitoring at the time of the PCT examination. The perfusion maps were quantitatively evaluated to detect DCI-related hypoperfusion. Possible clinical risk factors for the occurrence of DCI-related hypoperfusion in rPCT imaging were analyzed by multivariate analyses. RESULTS: One hundred thirty-six rPCTs were performed in 55 patients. New onset of DCI-related hypoperfusion was observed in 18% of rPCTs. The positive predictive value of rPCT to detect angiographic CVS was 0.80. Between examination days 6 and 10, the rate of DCI-related hypoperfusion was increased significantly (p < 0.05). After rPCT imaging with proof of DCI-related hypoperfusion, short-term follow-up showed secondary cerebral infarction (SCI) in 38%, compared with 5% for patients with normal perfusion on rPCT. The parameters "high risk phase (examination days 6-10)" and "new onset of DCI-related SCI" were significantly associated with the occurrence of DCI-related hypoperfusion in rPCT. CONCLUSIONS: In unconscious and asymptomatic aSAH patients, rPCT identifies DCI-related hypoperfusion in a relevant number of examinations. However, despite timely endovascular rescue therapy, a significant proportion of secondary infarction still occurs in this subgroup.

Cerebral Vasospasm After Spontaneous Subarachnoid Hemorrhage: Angiographic Pattern and Its Impact on the Clinical Course.

OBJECTIVE: To analyze angiographic characteristics of cerebral vasospasm (CVS) after spontaneous subarachnoid hemorrhage (sSAH) and their potential impact on secondary infarction and functional outcome. METHODS: Demographic, clinical, and imaging data of sSAH patients with angiographic CVS admitted over a 6-year period were retrospectively analyzed. RESULTS: A total of 85 patients were included in the final analysis. A total of 311 arterial territories in 85 angiographies demonstrated angiographic CVS. The anterior cerebral artery (ACA) was the most common site of angiographic CVS (42.1%), followed by the middle cerebral artery (MCA) (26.7%). In 29 angiographies (34%) CVS was found in more than 3 vessels and a bilateral pattern was identified in 53 cases (62%). Older age (OR 3.24 [95% CI 1.30-8.07], P = 0.012) was identified as the only significant risk factor for CVS-related infarction (OR 22.67, P = 0.015). Unfavorable outcome was associated with older age (OR 3.24, P = 0.023) and poor World Federation of Neurosurgical Societies grade (OR 3.64, P = 0.015). Analyses of angiographic characteristics did not reveal any risk factors for unfavorable outcome. We identified distal CVS as a significant risk factor for CVS-related infarction (OR 2.89, P = 0.026). CONCLUSIONS: Angiographic CVS after sSAH shows a specific distribution pattern in favor of ACA and MCA and in most cases 2-3 affected vessels are affected, often bilaterally. Patients exhibiting distal CVS have a higher risk for CVS-related infarction and should be observed closely. Nonetheless, the majority of angiographic characteristics did not allow conclusions about functional outcome nor the occurrence of CVS-related infarction in sSAH patients.

Management of tracheostomized patients after poor grade subarachnoid hemorrhage: Disease related and pulmonary risk factors for failed and delayed decannulation.

OBJECTIVE: Tracheostomy is often indicated in patients with spontaneous subarachnoid hemorrhage (sSAH). Decannulation is a major goal of neurorehabilitation, but cannot be achieved in all patients. The aim of this study was to describe the course of decannulation and to identify associated risk factors in a single-center collective. PATIENTS AND METHODS: We retrospectively reviewed 87 sSAH patients with WFNS (World Federation of Neurosurgical Societies) grade III-IV, who received tracheostomy. Decannulation events and the time from tracheostomy to decannulation were recorded in a 200-days follow-up. Variables analyzed were: age, sex, WFNS grade, Fisher grade, the presence of intracerebral or intraventricular hematoma, acute hydrocephalus, aneurysm location, aneurysm obliteration (surgical vs. endovascular), treatment related complications, decompressive craniectomy, symptomatic cerebral vasospasm, vasospasm-related infarction and timing of tracheostomy. Further risk factors analyzed were preexisting chronic lung disease and pneumonia. Functional outcome was assessed by the modified Rankin Scale (mRS). RESULTS: The rate of successful decannulation was 84% after a median of 47 days. A higher WFNS grade and pneumonia were associated with both a prolonged time to decannulation (TTD) and decannulation failure (DF). Older age (> 60 years) and necessity for decompressive craniectomy were only associated with prolonged TTD. Outcome analysis revealed that patients with DF show a significantly (p < 0.01) higher rate of unfavorable outcome (mRS 3-6). CONCLUSION: Successful decannulation is possible in the majority of sSAH patients and particularly, in all patients with WFNS grade III. WFNS grading, age, the necessity for decompressive craniectomy and pneumonia are significantly associated with the TTD. WFNS grade and pneumonia are significantly associated with DF. The mean cannulation time of sSAH patients is shorter in relation to stroke patients.

The appropriate management of persisting pain after spine surgery: a European panel study with recommendations based on the RAND/UCLA method.

PURPOSE: Management of patients with persisting pain after spine surgery (PPSS) shows significant variability, and there is limited evidence from clinical studies to support treatment choice in daily practice. This study aimed to develop patient-specific recommendations on the management of PPSS. METHODS: Using the RAND/UCLA appropriateness method (RUAM), an international panel of 6 neurosurgeons, 6 pain specialists, and 6 orthopaedic surgeons assessed the appropriateness of 4 treatment options (conservative, minimally invasive, neurostimulation, and re-operation) for 210 clinical scenarios. These scenarios were unique combinations of patient characteristics considered relevant to treatment choice. Appropriateness had to be expressed on a 9-point scale (1 = extremely inappropriate, 9 = extremely appropriate). A treatment was considered appropriate if the median score was ≥ 7 in the absence of disagreement (≥ 1/3 of ratings in each of the opposite sections 1-3 and 7-9). RESULTS: Appropriateness outcomes showed clear and specific patterns. In 48% of the scenarios, exclusively one of the 4 treatments was appropriate. Conservative treatment was usually considered appropriate for patients without clear anatomic abnormalities and for those with new pain differing from the original symptoms. Neurostimulation was considered appropriate in the case of (predominant) neuropathic leg pain in the absence of conditions that may require surgical intervention. Re-operation could be considered for patients with recurrent disc, spinal/foraminal stenosis, or spinal instability. CONCLUSIONS: Using the RUAM, an international multidisciplinary panel established criteria for appropriate treatment choice in patients with PPSS. These may be helpful to educate physicians and to improve consistency and quality of care. These slides can be retrieved under Electronic Supplementary Material.

The Impact of Intrahospital Transports on Brain Tissue Metabolism in Patients with Acute Brain Injury.

BACKGROUND: Patients with severe acute brain injury (ABI) often require intrahospital transports (IHTs) for repeated computed tomography (CT) scans. IHTs are associated with serious adverse events (AE) that might pose a risk for secondary brain injury. The goal of this study was to assess IHT-related alterations of cerebral metabolism in ABI patients. METHODS: We included mechanically ventilated patients with ABI who had continuous multimodality neuromonitoring during an 8-h period before and after routine IHT. Intracranial pressure (ICP), cerebral perfusion pressure (CPP), brain tissue oxygenation (PtiO2) as well as cerebral and subcutaneous microdialysis parameters (lactate, pyruvate, glycerol, and glutamate) were recorded. Values were compared between an 8-h period before (pre-IHT) and after (post-IHT) the IHT. RESULTS: A total of 23 IHT for head CT scans in 18 patients were analyzed. Traumatic brain injury (n = 7) was the leading cause of ABI, followed by subarachnoid hemorrhage (n = 6) and intracerebral hemorrhage (n = 5). The analyzed microdialysis parameters in the brain tissue as in the subcutaneous tissue did not show significant changes between the pre-IHT and post-IHT period. In addition, we observed no significant increase in ICP or decrease in CPP and PtiO2 in the 8-h period after IHT. CONCLUSIONS: While the occurrence of AE during IHT is a known risk factor for ABI patients, our results demonstrate that IHTs do not alter the brain tissue chemistry in a significant manner. This fact may help assess the risk for routine IHT more accurately.

Massive weight loss following deep brain stimulation of the nucleus accumbens in a depressed woman.

Obese individuals share behavioral characteristics with drug/alcohol addicts as well as obsessive compulsive disease. Deep brain stimulation (DBS) has been used successfully in these disorders, thus warranting an evaluation in obesity. A woman with treatment-resistant depression as well as severe obesity was selected for DBS of the nucleus accumbens (NAcc) bilaterally with depression being the primary and obesity being the secondary target of treatment. Compared to earlier bariatric surgery, the patient showed accelerated weight loss after DBS. Also, depression was significantly reduced. The current case suggests that DBS of the NAcc warrants further evaluation in patients unresponsive to other treatments.

Safety of Percutaneous Dilatational Tracheostomy in Patients with Acute Brain Injury and Reduced PaO2/FiO2 Ratio-Retrospective Analysis of 54 Patients.

OBJECTIVE: Percutaneous dilatational tracheostomy (PDT) is a commonly performed method in neurocritical care, and its safety has been proven in numerous studies. Nevertheless, data regarding the application in patients with acute brain injury and poor respiratory function are poor. The purpose of this study was to evaluate the incidence of hypoxemia and hypercapnia during PDT in those patients. METHODS: In a retrospective analysis, we acquired data from 54 patients with an acute brain injury (ABI) and a reduced PaO2/FiO2 ratio (PaO2/FiO2 < 300 mm Hg). In all cases, blood gas analyses before, during, and approximately 12 hours after PDT were available. We reviewed the patients' ventilator settings, results of gas exchange, and radiographic signs of acute respiratory distress syndrome (ARDS). Patients with ARDS were defined using the Berlin criteria. RESULTS: We observed 2 cases (3.6%) of intraoperative hypoxemia (PaO2 < 60 mm Hg) and 4 cases (7.4%) of intraoperative hypercapnia (PaCO2 > 55 mm Hg). Twenty patients fulfilled the Berlin criteria for ARDS. While mean PaO2 did not differ significantly between ARDS and non-ARDS patients, intraoperative hypoxemia only occurred in the ARDS group (2/20). Mean PaCO2 was similar in the ARDS and non-ARDS groups, and cases of hypercapnia were apparent in both groups. The mean PaO2/FiO2 ratio of all patients improved from 229.1 mm Hg before PDT to 255.3 mm Hg. CONCLUSIONS: Regarding the intraoperative gas exchange, indication of PDT in patients with ABI and ARDS should be considered carefully. However, PDT in ABI patients with reduced PaO2/FiO2 ratio alone appears to be a safe procedure.

Human subthalamic nucleus - Automatic auditory change detection as a basis for action selection.

The subthalamic nucleus (STN) shapes motor behavior and is important for the initiation and termination of movements. Here we ask whether the STN takes aggregated sensory information into account, in order to exert this function. To this end, local field potentials (LFP) were recorded in eight patients suffering from Parkinson's disease and receiving deep-brain stimulation of the STN bilaterally. Bipolar recordings were obtained postoperatively from the externalized electrode leads. Patients were passively exposed to trains of auditory stimuli containing global deviants, local deviants or combined global/local deviants. The surface event-related potentials of the Parkinson's patients as well as those of 19 age-matched healthy controls were characterized by a mismatch negativity (MMN) that was most pronounced for the global/local double deviants and less prominent for the other deviant conditions. The left and right STN LFPs similarly were modulated by stimulus deviance starting at about 100ms post-stimulus onset. The MMN has been viewed as an index of an automatic auditory change detection system, more recently phrased in terms of predictive coding theory, which prepares the organism for attention shifts and for action. The LFP-data from the STN clearly demonstrate that the STN receives information on stimulus deviance, possibly as a means to bias the system to interrupt ongoing and to allow alternative actions.

Deep brain stimulation versus motor cortex stimulation for neuropathic pain: A minireview of the literature and proposal for future research.

The treatment of neuropathic pain remains a public health concern. A growing cohort of patients is plagued by medically refractory, unrelenting severe neuropathic pain that ruins their quality of life and productivity. For this group, neurosurgery can offer two different kinds of neuromodulation that may help: deep brain simulation (DBS) and motor cortex stimulation (MCS). Unfortunately, there is no consensus on how to perform these procedures, which stimulation parameters to select, how to measure success, and which patients may benefit. This brief review highlights the literature supporting each technique and attempts to provide some comparisons and contrasts between DBS and MCS for the treatment of neuropathic pain. Finally, we highlight the current unanswered questions in the field and suggest future research strategies that may advance the care of our patients with neuropathic pain.

Clinical Significance of Invasive Motor Cortex Stimulation for Trigeminal Facial Neuropathic Pain Syndromes.

BACKGROUND: Invasive neuromodulation of the cortical surface for various chronic pain syndromes has been performed for >20 years. The significance of motor cortex stimulation (MCS) in chronic trigeminal neuropathic pain (TNP) syndromes remains unclear. Different techniques are performed worldwide in regard to operative procedure, stimulation parameters, test trials, and implanted materials. OBJECTIVE: To present the clinical experiences of a single center with MCS, surgical approach, complications, and follow-up as a prospective, noncontrolled clinical trial. METHODS: The implantation of epidural leads over the motor cortex was performed via a burr hole technique with neuronavigation and intraoperative neurostimulation. Special focus was placed on a standardized test trial with an external stimulation device and the implementation of a double-blinded or placebo test phase to identify false-positive responders. RESULTS: A total of 36 patients with TNP were operated on, and MCS was performed. In 26 of the 36 patients (72%), a significant pain reduction from a mean of 8.11 to 4.58 (on the visual analog scale) during the test trial was achieved (P < .05). Six patients were identified as false-positive responders (17%). At the last available follow-up of 26 patients (mean, 5.6 years), active MCS led to a significant pain reduction compared with the preoperative pain ratings (mean visual analog scale score, 5.01; P < .05). CONCLUSION: MCS is an additional therapeutic option for patients with refractory chronic TNP, and significant long-term pain suppression can be achieved. Placebo or double-blinded testing is mandatory. ABBREVIATIONS: MCS, motor cortex stimulationNRS, numeric pain rating scaleTNP, trigeminal neuropathic or deafferentation painVAS, visual analog scale.

Vagus Nerve Stimulation: Surgical Technique and Complications.

Chronic stimulation of the left vagus nerve (VNS) is commonly performed for different clinical conditions such as refractory epilepsy in children and adults, and major and bipolar depression. Despite more than 20 years of cumulative experience with VNS implantation, various surgery- and modality-related complications continue to occur in a sizable percentage of patients. A clear understanding of surgical anatomy and following standard operating protocol may, at least theoretically, reduce the number of complications. Here we present our way to perform VNS implantation and discuss different kinds of complications that each implanter should be aware of. Technical details of revision surgery are also presented.

Risk assessment of magnetic resonance imaging in chronically implanted paddle electrodes for cortical stimulation.

BACKGROUND: Cortical epidural stimulation is used for the treatment of different neuropsychiatric disorders such as chronic neuropathic pain, tinnitus, movement disorders, and psychiatric diseases. While preoperative magnetic resonance imaging (MRI) is considered the imaging tool of choice for planning the approach and electrode placement, postoperative MRI is still a contraindication with implanted paddle leads due to the risk of thermal damage or current induction creating seizures or neurological deficits. OBJECTIVES: In this feasibility in vitro study the temperature changes and induction were determined as well as the artifacts caused by 2 parallel paddle leads (Resume II, Model 3587 A; Medtronic, Minneapolis, Minn., USA), commonly used in clinical practice with and without a pulse generator (Prime Advanced, Model 7489; Medtronic). METHODS: An ultrasound gel-filled head phantom with 2 paddle leads mimicking the surgical scenario was used to evaluate temperature changes as well as induced currents in a 1.5- and 3-tesla MR scanner. In addition, 1 patient underwent a 3-tesla MRI with an implanted subdural paddle lead. RESULTS: Negligible temperature changes were detected with turbo spin echo sequences in the 1.5- and 3-tesla scanner using a head and body coil. Induced voltages up to 6 V were measured. The imaging artifacts in the phantom were well tolerable. The patient's imaging was uneventful under the settings which are accepted for deep brain stimulation imaging. CONCLUSION: MRI under the conditions described here seems to be safe with the implants used in this study. In particular, the induced temperature is much lower with paddle compared to conventional leads due to the different electrode design. The induced voltage does not carry any risks. However, these findings cannot automatically be transferred to other implants or other scanning conditions, and further studies are needed. The biomedical companies should be encouraged to develop MR-conditional paddle leads. Also, further research is necessary to study the mechanism of action of cortical stimulation in the future.

Current and future options for the management of phantom-limb pain.

Phantom-limb pain (PLP) belongs among difficult-to-treat chronic pain syndromes. Treatment options for PLP are to a large degree implicated by the level of understanding the mechanisms and nature of PLP. Research and clinical findings acknowledge the neuropathic nature of PLP and also suggest that both peripheral as well as central mechanisms, including neuroplastic changes in central nervous system, can contribute to PLP. Neuroimaging studies in PLP have indicated a relation between PLP and the neuroplastic changes. Further, it has been shown that the pathological neuroplastic changes could be reverted, and there is a parallel between an improvement (reversal) of the neuroplastic changes in PLP and pain relief. These findings facilitated explorations of novel neuromodulatory treatment strategies, adding to the variety of treatment approaches in PLP. Overall, available treatment options in PLP include pharmacological treatment, supportive non-pharmacological non-invasive strategies (eg, neuromodulation using transcranial magnetic stimulation, visual feedback therapy, or motor imagery; peripheral transcutaneous electrical nerve stimulation, physical therapy, reflexology, or various psychotherapeutic approaches), and invasive treatment strategies (eg, surgical destructive procedures, nerve blocks, or invasive neuromodulation using deep brain stimulation, motor cortex stimulation, or spinal cord stimulation). Venues of further development in PLP management include a technological and methodological improvement of existing treatment methods, an implementation of new techniques and products, and a development of new treatment approaches.

Altered somatosensory processing in trigeminal neuralgia.

Trigeminal neuralgia (TN) is a pain state characterized by intermittent unilateral pain attacks in one or several facial areas innervated by the trigeminal nerve. The somatosensory cortex is heavily involved in the perception of sensory features of pain, but it is also the primary target for thalamic input of nonpainful somatosensory information. Thus, pain and somatosensory processing are accomplished in overlapping cortical structures raising the question whether pain states are associated with alteration of somatosensory function itself. To test this hypothesis, we used functional magnetic resonance imaging to assess activation of primary (SI) and secondary (SII) somatosensory cortices upon nonpainful tactile stimulation of lips and fingers in 18 patients with TN and 10 patients with TN relieved from pain after successful neurosurgical intervention in comparison with 13 healthy subjects. We found that SI and SII activations in patients did neither depend on the affected side of TN nor differ between operated and nonoperated patients. However, SI and SII activations, but not thalamic activations, were significantly reduced in patients as compared to controls. These differences were most prominent for finger stimulation, an area not associated with TN. For lip stimulation SI and SII activations were reduced in patients with TN on the contra- but not on the ipsilateral side to the stimulus. These findings suggest a general reduction of SI and SII processing in patients with TN, indicating a long-term modulation of somatosensory function and pointing to an attempt of cortical adaptation to potentially painful stimuli.

Localizing and lateralizing language in patients with brain tumors: feasibility of routine preoperative functional MR imaging in 81 consecutive patients.

PURPOSE: To prospectively assess the feasibility of standardized presurgical functional magnetic resonance (MR) imaging for localizing the Broca and Wernicke areas and for lateralizing language function. MATERIALS AND METHODS: The study was approved by the responsible ethics commission, and patients gave written informed consent. Eighty-one patients (36 female and 45 male patients; age range, 7-75 years) with different brain tumors underwent blood oxygen level-dependent functional MR imaging at 1.5 T with two paradigms: sentence generation (SG) and word generation (WG). Functional MR imaging measurements, data processing, and evaluation were fully standardized by using dedicated software. Four regions of interest were evaluated in each patient: the Broca and Wernicke areas and their anatomic homologues in the right hemisphere. Statistics were calculated. RESULTS: The SG and WG paradigms were successfully completed by all (100%) and 70 (86%) patients, respectively. Success rates in localizing and lateralizing language were 96% for the Broca and Wernicke areas with the SG paradigm, 81% for the Broca area and 80% for the Wernicke area with the WG paradigm, and 98% for both areas when the SG and WG paradigms were used in combination. Functional localizations were consistent for SG and WG paradigms in the inferior frontal gyrus (Broca area) and the superior temporal, supramarginal, and angular gyri (Wernicke area). Surgery was not performed in seven patients (9%) and was modified in two patients (2%) because of functional MR imaging findings. CONCLUSION: Functional MR imaging proved to be feasible during routine diagnostic neuroimaging for localizing and lateralizing language function preoperatively.

Imaging of brain and brain tumor specimens by time-resolved multiphoton excitation microscopy ex vivo.

Multiphoton excitation fluorescent microscopy is a laser-based technology that allows subcellular resolution of native tissues in situ. We have recently applied this technology to the structural and photochemical imaging of cultured glioma cells and experimental gliomas ex vivo. We demonstrated that high microanatomical definition of the tumor, invasion zone, and normal adjacent brain can be obtained down to single-cell resolution in unprocessed tissue blocks. In this study, we used multiphoton excitation and four-dimensional microscopy to generate fluorescence lifetime maps of the murine brain anatomy, experimental glioma tissue, and biopsy specimens of human glial tumors. In murine brain, cellular and noncellular elements of the normal anatomy were identified. Distinct excitation profiles and lifetimes of endogenous fluorophores were identified for specific brain regions. Intracranial grafts of human glioma cell lines in mouse brain were used to study the excitation profiles and fluorescence lifetimes of tumor cells and adjacent host brain. These studies demonstrated that normal brain and tumor could be distinguished on the basis of fluorescence intensity and fluorescence lifetime profiles. Human brain specimens and brain tumor biopsies were also analyzed by multiphoton microscopy, which demonstrated distinct excitation and lifetime profiles in glioma specimens and tumor-adjacent brain. This study demonstrates that multiphoton excitation of autofluorescence can distinguish tumor tissue and normal brain based on the intensity and lifetime of fluorescence. Further technical developments in this technology may provide a means for in situ tissue analysis, which might be used to detect residual tumor at the resection edge.