The role of intra-operative motor evoked potentials in the optimization of chronic cortical stimulation for the treatment of neuropathic pain.

OBJECTIVE: To explore the significance of intra-operative motor evoked potentials (MEPs) obtained by monopolar and bipolar stimulation in determining the location of the electrode(s) giving most pain relief in chronic motor cortex stimulation (MCS). METHODS: Eight patients with chronic refractory neuropathic pain were implanted epidurally with two parallel leads of four electrodes each and placed normal to the central sulcus (CS). We measured the peak-peak amplitude (V(p-p)) of the MEPs recorded intra-operatively at the contralateral hand with the same stimulus delivered by each single electrode used as an anode or a cathode. Those electrodes giving the largest MEPs in monopolar stimulation were also tested in bipolar stimulation with an adjacent electrode located on the same or the other lead. It was analyzed whether a relation was present between the electrode providing the largest V(p-p) in the monopolar condition and the bipolar combination selected for chronic stimulation. RESULTS: In monopolar stimulation the median amplitude of MEPs evoked with an anode was 59% larger than with a cathode. The mean amplitude of the bipolarly evoked MEPs was only 21% and 37%, respectively, of the corresponding monopoles when the anode and cathode were separated by 6mm and by more than 8mm. A significant pain relief was obtained in 5 out of 8 patients post-operatively. In all these patients, one of the cathodes used in chronic stimulation was one of the anodes producing the largest MEP intra-operatively. Conversely, in the 3 patients who did not benefit from MCS, one of the cathodes used in chronic stimulation was one of the cathodes producing the largest MEPs intra-operatively. CONCLUSIONS: Monopolar stimulation should be applied in intra-operative neurophysiological testing because, contrary to bipolar stimulation, the corresponding MEPs are unambiguously related to a single stimulating electrode and their amplitude is not affected by the anode-cathode distance. The anode providing the largest MEPs intra-operatively should be selected as the cathode in chronic stimulation. However, implantable pulse generators allowing monopolar (cathodal and anodal) stimulation for MCS should become available to compare the respective analgesic efficacy of monopolar and bipolar chronic cortical stimulation. SIGNIFICANCE: Intra-operative MEP recordings can predict which electrode should be used as the cathode to obtain the best analgesic effect with chronic MCS.

Characterization of Pain in Familial Amyloid Polyneuropathy.

UNLABELLED: Familial amyloid polyneuropathy (FAP) caused by transthyretin (TTR) mutation is a small-fiber predominant polyneuropathy, exposing patients with TTR-FAP to development of neuropathic pain. However, the painful nature of TTR-FAP has never been specifically addressed. In this study, we compared 2 groups of 16 patients with either painless or painful TTR-FAP with regard to various clinical and neurophysiologic variables, including laser evoked potential (LEP) recording and quantitative sensory testing. The 2 groups of patients did not differ on any clinical or neurophysiologic variable. Patients with painful TTR-FAP complained of ongoing burning pain sensations, pain aggravation at rest, paroxysmal pain (electric shock and stabbing sensations), or provoked pain (mostly dynamic mechanical allodynia). However, the symptomatic presentation of painful TTR-FAP evolved with the course of the disease. The duration of the disease and the severity of small-fiber lesions (increase in thermal thresholds and reduction in LEP amplitude) correlated negatively with the intensity of ongoing burning sensations and positively with the intensity of paroxysmal pain. In addition, small-fiber preservation correlated positively with cold allodynia and pain aggravation at rest and negatively with dynamic mechanical allodynia. Peripheral sensitization of small-diameter nociceptive axons might occur in early TTR-FAP and be responsible for the burning sensation and cold allodynia. As polyneuropathy and small-fiber loss progress, paroxysmal pain and dynamic mechanical allodynia may develop as a result of central sensitization generated by abnormal activities affecting relatively spared large-diameter sensory fibers. PERSPECTIVE: Pain in TTR-FAP includes several mechanisms varying with the course of the disease and the involvement of the different types of nerve fibers.

Spinal stimulation for movement disorders.

Epidural spinal cord stimulation (SCS) is currently proposed to treat intractable neuropathic pain. Since the 1970s, isolated cases and small cohorts of patients suffering from dystonia, tremor, painful leg and moving toes (PLMT), or Parkinson's disease were also treated with SCS in the context of exploratory clinical studies. Despite the safety profile of SCS observed in these various types of movement disorders, the degree of improvement of abnormal movements following SCS has been heterogeneous among patients and across centers in open-label trials, stressing the need for larger, randomized, double-blind studies. This article provides a comprehensive review of both experimental and clinical studies of SCS application in movement disorders.

Sensory correlates of pain in peripheral neuropathies.

OBJECTIVE: To characterize sensory threshold alterations in peripheral neuropathies and the relationship between these alterations and the presence of pain. METHODS: Seventy-four patients with length-dependent sensory axonal neuropathy were enrolled, including 38 patients with painful neuropathy (complaining of chronic, spontaneous neuropathic pain in the feet) and 36 patients with painless neuropathy. They were compared to 28 age-matched normal controls. A standardized quantitative sensory testing protocol was performed in all individuals to assess large and small fiber function at the foot. Large fibers were assessed by measuring mechanical (pressure and vibration) detection thresholds and small fibers by measuring pain and thermal detection thresholds. RESULTS: Between patients with neuropathy and controls, significant differences were found for mechanical and thermal detection thresholds but not for pain thresholds. Patients with painful neuropathy and those with painless neuropathy did not differ regarding mechanical or thermal thresholds, but only by a higher incidence of thermal or dynamic mechanical allodynia in case of painful neuropathy. Pain intensity correlated with the alteration of thermal detection and mechanical pain thresholds. CONCLUSIONS: Quantitative sensory testing can support the diagnosis of sensory neuropathy when considering detection threshold measurement. Thermal threshold deterioration was not associated with the occurrence of pain but with its intensity. SIGNIFICANCE: There is a complex relationship between the loss or functional deficit of large and especially small sensory nerve fibers and the development of pain in peripheral neuropathy.

Predictive value of rTMS in the identification of responders to epidural motor cortex stimulation therapy for pain.

UNLABELLED: This study was designed to assess the value of repetitive transcranial magnetic stimulation (rTMS) to predict the efficacy of epidural motor cortex stimulation (EMCS) to treat neuropathic pain. We have included 59 patients treated by EMCS for more than 1 year and in whom active and sham 10Hz-rTMS sessions were performed as preoperative tests, targeted over the cortical representation of the painful area. Analgesic effects were rated on a visual analogue scale. The real rTMS efficacy was determined by subtracting the effect of the sham stimulation on pain scores from that of the active stimulation (active-sham calculation). Pain scores were significantly reduced by active rTMS and EMCS, but not by sham rTMS. Twenty-six of the 33 patients (79%) who responded to active rTMS and all the 21 patients (100%) who responded for active-sham calculation also responded to EMCS. The response observed in active-sham calculation had a positive predictive value of 1.0, but a negative predictive value of .6 regarding EMCS outcome. The analgesic effect of rTMS or EMCS was not influenced by the side, origin, or duration of pain or by the presence of motor or sensory deficit in the painful area. Poorer results were observed in case of lower limb pain for rTMS and in older patients for EMCS. This study confirms that neuropathic pain can be significantly relieved by motor cortex rTMS or EMCS. A positive outcome of EMCS can be predicted by a real response to rTMS, but not on clinical grounds. PERSPECTIVE: Single sessions of sham-controlled preoperative rTMS tests can be used to confirm the indication of EMCS therapy but have no value to exclude patients from this therapy. New rTMS protocols remain to be assessed to improve the usefulness of preoperative rTMS in EMCS practice.

Descending volleys generated by efficacious epidural motor cortex stimulation in patients with chronic neuropathic pain.

Epidural motor cortex stimulation (EMCS) is a therapeutic option for chronic, drug-resistant neuropathic pain, but its mechanisms of action remain poorly understood. In two patients with refractory hand pain successfully treated by EMCS, the presence of implanted epidural cervical electrodes for spinal cord stimulation permitted to study the descending volleys generated by EMCS in order to better appraise the neural circuits involved in EMCS effects. Direct and indirect volleys (D- and I-waves) were produced depending on electrode polarity and montage and stimulus intensity. At low-intensity, anodal monopolar EMCS generated D-waves, suggesting direct activation of corticospinal fibers, whereas cathodal EMCS generated I2-waves, suggesting transsynaptic activation of corticospinal tract. The bipolar electrode configuration used in chronic EMCS to produce maximal pain relief generated mostly I3-waves. This result suggests that EMCS induces analgesia by activating top-down controls originating from intracortical horizontal fibers or interneurons but not by stimulating directly the pyramidal tract. The descending volleys elicited by bipolar EMCS are close to those elicited by transcranial magnetic stimulation using a coil with posteroanterior orientation. Different pathways are activated by EMCS according to stimulus intensity and electrode montage and polarity. Special attention should be paid to these parameters when programming EMCS for pain treatment.

Cerebrovascular diseases in HIV-infected patients.

Cerebrovascular disease (CVD) has early been recognized in HIV-infected patients, including infectious arteritis, inflammatory vasculitis, aneurismal and small-vessel arteriopathy, to which adds now the premature atherosclerotic cerebral arteriopathy associated with the highly active antiretroviral therapy (HAART)-induced metabolic disorders. As a result of the increased life-expectancy associated with HAART, HIV patients grow older and are exposed to the combined vascular risk of antiviral-induced metabolic changes and advancing age. Several studies have documented subclinical cervical artery atherosclerosis, as assessed by intima-media thickness, ultrasound detection of carotid artery plaques and intracerebral small-vessel disease, all being associated with the induced metabolic changes. This suggests that vascular prevention should be performed on a long-term basis.