Colette Goujon

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.

Analgesic effects of repetitive transcranial magnetic stimulation of the motor cortex in neuropathic pain: Influence of theta burst stimulation priming

‘Conventional’ protocols of high‐frequency repetitive transcranial magnetic stimulation (rTMS) delivered to M1 can produce analgesia. Theta burst stimulation (TBS), a novel rTMS paradigm, is thought to produce greater changes in M1 excitability than ‘conventional’ protocols. After a preliminary experiment showing no analgesic effect of continuous or intermittent TBS trains (cTBS or iTBS) delivered to M1 as single procedures, we used TBS to prime a subsequent session of ‘conventional’ 10 Hz‐rTMS.

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.

Spinal cord stimulation for chronic pain improved motor function in a patient with Parkinson's disease.

Spinal cord stimulation (SCS) is a validated therapy for various chronic pain syndromes [1] that was recently shown to improve locomotor behaviour in rodent model of Parkinson’s disease (PD) [2]. We report herein the antiparkinsonian effect of SCS in a patient implanted for lower limb neuropathic painwho later developed PD. A 74-year oldmanwas successfully treated since the age of 61 by SCS implanted at T9-T10 level for a failed back surgery syndrome. Parameters of stimulation were as follows: 70–100 Hz frequency, 410 ms pulse width, 3.5 V (Symmix quadripolar electrode and Itrel-3 pulse generator, Medtronic, Inc., Minneapolis, USA). At the age of 69, the patient developed a tremor-dominant type of PD predominating on right side. A [123-I]FP-CIT dopamine transporter SPECT imaging showed asymmetric striatal loss of binding consistent with PD. Tremor was partially controlled by levodopa (1200 mg/day). We assessed the effect of SCS on motor PD symptoms in four sessions (two to five weeks apart) after overnight dopaminergic medication withdrawal. In sessions 1, 2, and 4, the patient was successively evaluated in offand on-stimulation conditions, while he remained off-drug. In session 3, offand onstimulation conditions were tested before and after (off-/on-drug) the administration of a single suprathreshold dose of levodopa/carbidopa (350/35 mg). SCS frequency was set at 130 Hz (the highest frequency allowed by the generator) during the sessions, but was left at 100 Hz between the sessions, except between sessions 3 and 4 where SCS frequency was maintained at 130 Hz for five weeks. All examinations were performed while SCS was switched on or off for 30–60 min. Outcome measures were the motor score of the Unified Parkinson’s Disease Rating Scale (UPDRS-III), time to walk 7 m, turn, and walk back, and pain level in the lower limbs scored on a 0–10 visual analogue scale. In session 3, tremor was assessed using surface EMG recordings. All motor features, with the exception of rigidity, were videotaped and independently rated by two blinded neurologists who had to agree on the final score. Rigidity was rated by consensus between the two neurologists who performed the tests. Double-blind evaluationwas not feasible, since the patient felt paresthesiae and pain relief in the lower limbs when the stimulator was on. The study was approved by the local ethics committee.

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.

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.

Analgesic effects of navigated motor cortex rTMS in patients with chronic neuropathic pain.

Repetitive transcranial magnetic stimulation (rTMS) can relieve neuropathic pain when applied at high frequency (HF: 5–20 Hz) over the primary motor cortex (M1), contralateral to pain side. In most studies, rTMS is delivered over the hand motor hot spot (hMHS), whatever pain location. Navigation systems have been developed to guide rTMS targeting, but their value to improve rTMS efficacy remains to be demonstrated.

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.

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.

CSF-Shunt-Related Thrombophlebitis—Case Reports:

Two cases of left upper extremity thrombophlebitis following left cerebrospi nal fluid, (CSF) shunt implantation are reported. Signs and symptoms appeared in the early postoperative period (at days 5 and 15 respectively). Thrombosis of the axillary vein was demonstrated by Doppler examination and phlebography. Both patients were given anticoagulant therapy with a favor able clinical outcome . No pulmonary embolism or catheter dysfunction occurred. The patients remained free of any disability after a two and three-year follow-up, respectively, without relapsing thrombosis after discontinuation of therapy. These 2 cases occurred in the only 2 adult-patients in whom a left CSF shunt was implanted. No thrombotic complications occurred among 153 patients with a right implantation of the device. Thus, the course of the catheter through the left brachiocephalic vein has to be taken into account in the pathogenicity of this complication.