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.

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.

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.

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.

Motor cortex stimulation for long-term relief of chronic neuropathic pain: a 10 year experience.

Chronic subthreshold stimulation of the contralateral precentral gyrus is used in patients with intractable neuropathic pain for more than 15 years. The aim of this study was to analyse retrospectively our own patient group with long term follow-up of 10 years. Seventeen patients with chronic neuropathic pain were treated with contralateral epidural stimulation electrodes. In 10 cases, trigeminal neuropathic pain (TNP) and in seven cases post-stroke pain (PSP) were diagnosed. The placement of the electrodes was performed in local anaesthesia using neuronavigation and intraoperative neuromonitoring. A test trial of minimum one week including double-blind testing was conducted and pain intensity was measured using a visual analogue scale (VAS). Correct placement of the electrode was achieved in all patients using intraoperative neurophysiological monitoring. Double-blind testing was able to identify 6 (35%) non-responders. In 5 of 10 (50%) with TNP and 3 of 7 (43%) with PSP a positive effect with pain reduction > or = 50% was observed. The mean follow-up period was 3.6 years (range 1-10 years) and includes a patient with 10 years of positive stimulation effect. Stimulation of the motor cortex is a treatment option for patients with chronic neuropathic pain localized in the face or upper extremity. Double-blind testing can identify non-responders. Patients with TNP profit more than patients with PSP. The positive effect can last for ten years in long-term follow-up.

Deep brain stimulation for the treatment of various chronic pain syndromes.

OBJECT: Electrical intracerebral stimulation (also referred to as deep brain stimulation [DBS]) is a tool for the treatment of chronic pain states that do not respond to less invasive or conservative treatment options. Careful patient selection, accurate target localization, and identification with intraoperative neurophysiological techniques and blinded test evaluation are the key requirements for success and good long-term results. The authors present their experience with DBS for the treatment of various chronic pain syndromes. METHODS: In this study 56 patients with different forms of neuropathic and mixed nociceptive/neuropathic pain syndromes were treated with DBS according to a rigorous protocol. The postoperative follow-up duration ranged from 1 to 8 years, with a mean of 3.5 years. Electrodes were implanted in the somatosensory thalamus and the periventricular gray region. Before implantation of the stimulation device, a double-blinded evaluation was carefully performed to test the effect of each electrode on its own as well as combined stimulation with different parameter settings. The best long-term results were attained in patients with chronic low-back and leg pain, for example, in so-called failed-back surgery syndrome. Patients with neuropathic pain of peripheral origin (such as complex regional pain syndrome Type II) also responded well to DBS. Disappointing results were documented in patients with central pain syndromes, such as pain due to spinal cord injury and poststroke pain. Possible reasons for the therapeutic failures are discussed; these include central reorganization and neuroplastic changes of the pain-transmitting pathways and pain modulation centers after brain and spinal cord lesions. CONCLUSIONS: The authors found that, in carefully selected patients with chronic pain syndromes, DBS can be helpful and can add to the quality of life.

Subthalamic nucleus stimulation affects a frontotemporal network: a PET study.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has become an effective strategy in the treatment of motor symptoms in advanced Parkinson's disease. However, clinical studies have shown that DBS can affect verbal fluency. Seven Parkinson's disease patients with bilateral DBS of the STN were studied with positron emission tomography (PET) to investigate the effects of STN stimulation on regional cerebral blood flow during a verbal fluency task. Activation of the right orbitofrontal cortex and verbal fluency-associated activation within a left-sided frontotemporal network were decreased during STN stimulation compared with the OFF state. Our results offer an explanation for the commonest neuropsychological side effect of STN stimulation and show that STN stimulation affects a frontotemporal network during a fluency task.