Transcranial magnetic stimulation studies in complex regional pain syndrome type I: A review.

The sensory and motor cortical representation corresponding to the affected limb is altered in patients with complex regional pain syndrome (CRPS). Transcranial magnetic stimulation (TMS) represents a useful non-invasive approach for studying cortical physiology. If delivered repetitively, TMS can also modulate cortical excitability and induce long-lasting neuroplastic changes. In this review, we performed a systematic search of all studies using TMS to explore cortical excitability/plasticity and repetitive TMS (rTMS) for the treatment of CRPS. Literature searches were conducted using PubMed and EMBASE. We identified 8 articles matching the inclusion criteria. One hundred fourteen patients (76 females and 38 males) were included in these studies. Most of them have applied TMS in order to physiologically characterize CRPS type I. Changes in motor cortex excitability and brain mapping have been reported in CRPS-I patients. Sensory and motor hyperexcitability are in the most studies bilateral and likely involve corresponding regions within the central nervous system rather than the entire hemisphere. Conversely, sensorimotor integration and plasticity were found to be normal in CRPS-I. TMS examinations also revealed that the nature of motor dysfunction in CRPS-I patients differs from that observed in patients with functional movement disorders, limb immobilization, or idiopathic dystonia. TMS studies may thus lead to the implementation of correct rehabilitation strategies in CRPS-I patients. Two studies have begun to therapeutically use rTMS. This non-invasive brain stimulation technique could have therapeutic utility in CRPS, but further well-designed studies are needed to corroborate initial findings.

rTMS of the prefrontal cortex has analgesic effects on neuropathic pain in subjects with spinal cord injury.

STUDY DESIGN: Repetitive transcranial magnetic stimulation study. OBJECTIVES: The analgesic effects of repetitive transcranial magnetic stimulation (rTMS) in chronic pain have been the focus of several studies. In particular, rTMS of the premotor cortex/dorsolateral prefrontal cortex (PMC/DLPFC) changes pain perception in healthy subjects and has analgesic effects in acute postoperative pain, as well as in fibromyalgia patients. However, its effect on neuropathic pain in patients with traumatic spinal cord injury (SCI) has not been assessed. SETTING: Merano (Italy) and Salzburg (Austria). METHODS: In this study, we performed PMC/DLPFC rTMS in subjects with SCI and neuropathic pain. Twelve subjects with chronic cervical or thoracic SCI were randomized to receive 1250 pulses at 10 Hz rTMS (n=6) or sham rTMS (n=6) treatment for 10 sessions over 2 weeks. The visual analog scale, the sensory and affective pain rating indices of the McGill Pain Questionnaire (MPQ), the Hamilton Depression Rating Scale and the Hamilton Anxiety Rating Scale were used to assed pain and mood at baseline (T0), 1 day after the first week of treatment (T1), 1 day (T2), 1 week (T3) and 1 month (T4) after the last intervention. RESULTS: Subjects who received active rTMS had a statistically significant reduction in pain symptoms in comparison with their baseline pain, whereas sham rTMS participants had a non-significant change in daily pain from their baseline pain. CONCLUSION: The findings of this preliminary study in a small patient sample suggest that rTMS of the PMC/DLPFC may be effective in relieving neuropathic pain in SCI patients.

The contribution of neurophysiology in the diagnosis and management of cervical spondylotic myelopathy: a review.

STUDY DESIGN: Topical review of the literature. OBJECTIVE: The objective of this review article was to assess indications and usefulness of various neurophysiological techniques in diagnosis and management of cervical spondylogenic myelopathy (CSM). METHODS: The MEDLINE, accessed by Pubmed and EMBASE electronic databases, was searched using the medical subject headings: 'compressive myelopathy', 'cervical spondylotic myelopathy (CSM)', 'cervical spondylogenic myelopathy', 'motor evoked potentials (MEPs)', 'transcranial magnetic stimulation', 'somatosensory evoked potentials (SEPs)', 'electromyography (EMG)', 'nerve conduction studies (NCS)' and 'cutaneous silent period (CSP)'. RESULTS: SEPs and MEPs recording can usefully supplement clinical examination and neuroimaging findings in assessing the spinal cord injury level and severity. Segmental cervical cord dysfunction can be revealed by an abnormal spinal N13 response, whereas the P14 potential is a reliable marker of dorsal column impairment. MEPs may also help in the differential diagnosis between spinal cord compression and neurodegenerative disorders. SEPs and MEPs are also useful in follow-up evaluation of sensory and motor function during surgical treatment and rehabilitation. EMG and NCS improve the sensitivity of cervical radiculopathy detection and may help rule out peripheral nerve problems that can cause symptoms that are similar to those of CSM. CSP also shows a high sensitivity for detecting CSM. CONCLUSION: Neuroimaging, especially magnetic resonance imaging, represents the procedure of choice for the diagnosis of CSM, but a correct interpretation of morphological findings can be achieved only if they are correlated with functional data. The studies reported in this review highlight the crucial role of the electrophysiological studies in diagnosis and management of CSM.

Central motor and sensory conduction in patients with hepatic myelopathy.

STUDY DESIGN: Experimental neurophysiological study. OBJECTIVES: The hepatic myelopathy (HM) is characterized by progressive weakness and spasticity of the lower extremities, while there are only a few reports of sensory impairment. However, sensory function has been poorly explored in HM. We believe that an electrophysiological assessment of dorsal columns by somatosensory evoked potentials (SEPs) and of cortico-spinal lateral tracts by motor evoked potentials (MEPs) should be of considerable value in the functional evaluation of the spinal cord involvement in patients with HM. SETTING: Salzburg (Austria) and Merano (Italy). METHODS: Eight patients diagnosed with HM were studied with MEPs and SEPs. Neurological examination revealed different degrees of cortico-spinal tract involvement in all patients and sensory abnormalities in three patients. RESULTS: Central motor conduction to lower limb muscles was abnormal in all patients, while central sensory conduction was abnormal in seven out of the eight patients. Both central motor and sensory conduction to upper limbs are normal in all patients. CONCLUSION: The main finding is that electrophysiological evidence of central sensory involvement is present in a very high percentage of patients with HM, and that the threshold for electrophysiological abnormalities is below that for clinical manifestations. Therefore, central sensory and motor conduction studies are sensitive methods for detecting, localizing and monitoring spinal cord damage in HM.

[Role of duplex ultrasonography of the ophthalmic artery in internal carotid artery stenosis]. / Die Rolle der Duplexsonographie der Arteria ophthalmica bei Stenosen der Arteria carotis interna.

BACKGROUND: Duplex sonographic visualization of a retrogradely perfused ophthalmic artery (AO) as an expression of an existing collateral supply in high-grade stenosis of the internal carotid artery (ACI) is a widely used and validated tool. After revascularization there may be another reversal of flow. Recently, the question of whether knowledge of the flow direction of the AO before and after implantation of a stent can be used as an outcome predictor has been posed more frequently. METHODS AND RESULTS: In this article, the method of duplex sonographic assessment of the AO is explained more elaborately and we present a case of a patient with 75% restenosis of the left ACI with contralateral chronic occlusion of the right ACI. We focus on the special aspect that the ipsilateral AO was initially perfused retrogradely and that postinterventionally there was a flow reversal to a physiological anterograde flow. The case report is used to illustrate the value of duplex sonographic visualization of the AO. CONCLUSION: Our case report is able to illustrate two aspects: On the one hand, the AO can be perfused retrogradely in the specific case of chronic ACI occlusion of the opposite side, even when the ACI stenosis of the considered side is less than 80%. On the other hand, the AO can offer added diagnostic value as a follow-up parameter for re- or in-stent stenoses.

Post-processing of real-time quantum event measurements for an optimal bandwidth.

Single electron tunneling and its transport statistics have been studied for some time using high precision charge detectors. However, this type of detection requires advanced lithography, optimized material systems and low temperatures (mK). A promising alternative, recently demonstrated, is to exploit an optical transition that is turned on or off when a tunnel event occurs. High bandwidths should be achievable with this approach, although this has not been adequately investigated so far. We have studied low temperature resonance fluorescence from a self-assembled quantum dot embedded in a diode structure. We detect single photons from the dot in real time and evaluate the recorded data only after the experiment, using post-processing to obtain the random telegraph signal of the electron transport. This is a significant difference from commonly used charge detectors and allows us to determine the optimal time resolution for analyzing our data. We show how this post-processing affects both the determination of tunneling rates using waiting-time distributions and statistical analysis using full-counting statistics. We also demonstrate, as an example, that we can analyze our data with bandwidths as high as 175 kHz. Using a simple model, we discuss the limiting factors for achieving the optimal bandwidth and propose how a time resolution of more than 1 MHz could be achieved.

Sonographic and ophthalmic assessment of optic nerve in patients with idiopathic intracranial hypertension: A longitudinal study.

BACKGROUND: To assess the validity of neurosonological parameters (transorbital sonography (TOS)) for detection and monitoring of patients with idiopathic intracranial hypertension (IIH). METHODS: Prospective, single-center, case-controlled study in 25 patients with IIH and 19 controls. Visual parameters of papilledema, visual acuity, computerized static threshold perimetry, fundus examination, and neurosonological parameters of papilledema/optic disc elevation (ODE), optic nerve sheath diameter (ONSD) and optic nerve diameter (OND) were recorded at baseline and only for patients with IIH again within 6 months. RESULTS: ONSD was significantly enlarged among individuals with IIH (6.2 ± 0.73 mm) compared to controls (4.99 ± 0.54 mm; p < 0.001). Bilateral ODE was found in 36/50 eyes in patients at their initial visit and in none of the controls. Re-evaluation 6 months later showed a significant reduction of ONSD (6.0 ± 0.7 mm; p = 0.024) and ODE (0.2 (0-1) mm; p ≤0.001). Best corrected visual acuity (BCVA) and square root of lost variance (sLV) remained stable. Headache intensity (Numeric rating scale, NRS) improved significantly p < 0.001. When compared to patients with first diagnosed IIH (n = 18), the subset of patients with preexisting IIH with acute relapse (n = 7) showed persistent but reduced levels of ICP increase. They also presented significant decrease of BVCA (p = 0.01) and mean defect (MD) (p = 0.012). Re-evaluation 6 months later showed significant change in ODE in both groups. CONCLUSIONS: Our study confirmed that TOS and ophthalmological parameters are a valuable and non-invasive method to detect and monitor elevated ICP in IIH.

Effects of Subthalamic Nucleus Deep Brain Stimulation on Facial Emotion Recognition in Parkinson's Disease: A Critical Literature Review.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective therapy for Parkinson's disease (PD). Nevertheless, DBS has been associated with certain nonmotor, neuropsychiatric effects such as worsening of emotion recognition from facial expressions. In order to investigate facial emotion recognition (FER) after STN DBS, we conducted a literature search of the electronic databases MEDLINE and Web of science. In this review, we analyze studies assessing FER after STN DBS in PD patients and summarize the current knowledge of the effects of STN DBS on FER. The majority of studies, which had clinical and methodological heterogeneity, showed that FER is worsening after STN DBS in PD patients, particularly for negative emotions (sadness, fear, anger, and tendency for disgust). FER worsening after STN DBS can be attributed to the functional role of the STN in limbic circuits and the interference of STN stimulation with neural networks involved in FER, including the connections of the STN with the limbic part of the basal ganglia and pre- and frontal areas. These outcomes improve our understanding of the role of the STN in the integration of motor, cognitive, and emotional aspects of behaviour in the growing field of affective neuroscience. Further studies using standardized neuropsychological measures of FER assessment and including larger cohorts are needed, in order to draw definite conclusions about the effect of STN DBS on emotional recognition and its impact on patients' quality of life.

Abnormal intracortical facilitation in early-stage Huntington's disease.

OBJECTIVE: It is known from neuropathological and imaging studies that the neuronal degeneration in Huntington's disease (HD) is already quite severe when the first symptoms of the disease become clinically evident. This study was aimed at detecting neurophysiological changes, as assessed by means of transcranial magnetic stimulation (TMS), involved in the early pathogenesis of the neurodegeneration in HD. METHODS: Motor cortex excitability was examined in 12 patients with HD in the early clinical stage of the disease and in 15 age-matched control subjects, using a range of TMS protocols. Central motor conduction time, resting and active motor threshold, duration of the cortical silent period, the short-interval paired-pulse intracortical inhibition (SICI) and the paired-pulse intracortical facilitation (ICF) were examined. RESULTS: The early-stage HD patients showed a statistically significant reduction in ICF. The other measures did not differ significantly from the control subjects. CONCLUSIONS: Our findings provide neurophysiological evidence that changes in motor function are present in the early HD. Since ICF is thought to depend upon the activity of intracortical glutamatergic excitatory circuits, the results of our study support the theory that altered NMDA receptor function plays an important role in the pathogenesis of HD. SIGNIFICANCE: These findings may provide clues to the underlying pathophysiology of the disease. A more complete understanding of the changes in motor cortex excitability that occur early in the course of HD will lead to a better definition of the disease process and may allow earlier diagnosis and intervention.

Transcranial magnetic stimulation shows impaired transcallosal inhibition in Marchiafava-Bignami syndrome.

A case of Marchiafava-Bignami (MB) syndrome with selective callosal involvement was evaluated by clinical examination and magnetic resonance imaging (MRI) in the acute phase and 6 months after the onset of symptoms; at the same time, the corticospinally and transcallosally mediated effects elicited by transcranial magnetic stimulation (TMS) were investigated. The first MRI study showed the presence of extensive abnormal signal intensity throughout the entire corpus callosum. After high-dose corticosteroid administration her symptoms rapidly resolved, in parallel with the reversion of MRI changes, except for severe cognitive impairment. Follow-up TMS examination revealed persistent transcallosal inhibition (TI) abnormalities. This report indicates that the measurement of TI during the course of MB syndrome is useful for evaluating functional changes to the corpus callosum, including their evaluation with time and after treatment and for elucidating the pathophysiology of MB syndrome.

Changes in motor cortical excitability in humans following orally administered theophylline.

The effects of theophylline on human corticospinal excitability were studied using transcranial magnetic stimulation (TMS) before and after double-blind oral administration of theophylline or placebo in 20 healthy volunteers. TMS measurements included resting and active motor threshold, silent period, intracortical inhibition (ICI), and intracortical facilitation. F-wave and compound muscle action potential (CMAP) were also measured. Theophylline produces a reduction in ICI, while other parameters of corticospinal excitability remained unaffected. Since ICI is thought to depend on GABAA intracortical inhibitory mechanisms, our data suggest that the increase of human motor cortex excitability is the result of a decrease in GABAergic transmission. Our results further support the hypothesis that theophylline might induce convulsions by inhibiting GABAA receptor binding.

Partial visual feedback and spatial end-point accuracy of discrete aiming movements.

Five experiments are reported in which the effect of partial visual feedback on the accuracy of discrete target aiming was investigated. Visual feedback was manipulated through a spectacle-mounted liquid-crystal tachistoscope. The length of the visual feedback interval was varied as a percentage of the instructed movement time. In Experiment 1, the length of the vision interval was manipulated symmetrically at the beginning- and end-phase of the movement, whereas in the remaining experiments, the vision time was varied with respect to the end-phase only. The variations at the end were examined for different distances (Experiment 2), different movement speeds at the same distance (Experiment 3), and in small interstep intervals (Experiment 4). A vision time of more than 150 ms at the end-phase of the movement enhanced aiming performance in all experiments. Longer vision times monotonously improved aiming accuracy; the fifth experiment showed that a vision time of about 275 ms was sufficient for near-perfect aiming. Furthermore, the significance of vision during the first phase of a movement was demonstrated again. The results of the five experiments pointed to shorter visuomotor processing times. To explain the beneficial effects of short vision times for aiming accuracy, we propose a model of visuomotor processing that is based on the stochastic optimized submovement model of Meyer, Abrams, Kornblum, Wright, and Smith (1988).

Hemiparkinson-hemiatrophy syndrome: a transcranial magnetic stimulation study.

We described the clinical and neuroradiological findings together with a transcranial magnetic stimulation study in two patient with hemiparkinson-hemiatrophy syndrome (HP-HA). In both patients the neuroradiological findings (MRI) and the central motor conduction were normal whereas the functional imaging studies (SPECT) showed asymmetrical perfusion in the basal ganglia; the intracortical inhibition at short interstimulus intervals and the silent period duration in the motor cortex contralateral to hemiparkinsonism were significantly increased only in one of the patient which has a poor response to L-Dopa therapy. These studies suggest that intracortical or thalamo-cortical neuronal inhibition may be increased in HP-HA. The etiopathogenetic considerations, the diagnostic criteria and the prognostic value of our finding to evaluate the clinical evolution of parkinsonism are discussed in the context of current models of basal ganglia-thalamo-cortical connectivity. Transcranial magnetic stimulation will provide valuable information for the differential diagnosis of the parkinsonian disorders and may predict the efficacy of L-Dopa therapy.

Transorbital sonography in acute optic neuritis: a case-control study.

BACKGROUND AND PURPOSE: Acute unilateral optic neuritis is associated with a thickening of the retrobulbar portion of the optic nerve as revealed by transorbital sonography, but no comparison has been made between nerve sheath diameter and optic nerve diameter in patients with acute optic neuritis versus healthy controls. We evaluated optic nerve sheath diameter and optic nerve diameter in patients with acute optic neuritis and healthy controls and compared optic nerve sheath diameter and optic nerve diameter with visual-evoked potentials in patients. MATERIALS AND METHODS: A case-control study was performed in 2 centers. Twenty-one consecutive patients with onset of visual loss during the prior 10 days and established acute noncompressive unilateral optic neuritis were compared with 21 healthy controls, matched for sex and age (±5 years). Two experienced vascular sonographers performed the study by using B-mode transorbital sonography. Visual-evoked potentials were performed on the same day as the transorbital sonography and were evaluated by an expert neurophysiologist. Sonographers and the neurophysiologist were blinded to the status of the patient or control and to clinical information, including the side of the affected eye. RESULTS: The median optic nerve sheath diameter was thicker on the affected side (6.3 mm; interquartile range, 5.9-7.2 mm) compared with the nonaffected side (5.5 mm; interquartile range, 5.1-6.2 mm; P < .0001) and controls (5.2 mm; interquartile range, 4.8-5.5 mm; P < .0001). The median optic nerve diameter was 3.0 mm (range, 2.8-3.1 mm) on the affected side and 2.9 mm (range, 2.8-3.1 mm) on the nonaffected side (P = not significant.). Both sides were thicker than those in controls (2.7 mm; interquartile range, 2.5-2.8 mm; P = .001 and .009). No correlation was found between optic nerve sheath diameter and optic nerve diameter and amplitude and latency of visual-evoked potentials in patients with optic neuritis. CONCLUSIONS: Transorbital sonography is a promising tool to support the clinical diagnosis of acute optic neuritis. Further studies are needed to define its specific role in the diagnosis and follow-up of optic neuritis.

Transitory stapedial myoclonus in a patient with benign fasciculation syndrome.

OBJECTIVE: We report a previously undescribed association between transitory stapedial myoclonus, objective tinnitus and benign fasciculation syndrome. METHOD: Case report and review of the world literature regarding stapedial myoclonus. RESULTS: A 30-year-old man with a diagnosis of benign fasciculation syndrome abruptly developed severe, low-pitched tinnitus on the right side. Otoscopic examination revealed rhythmic movement of the tympanic membrane, which was synchronous with the tinnitus. No palatal spasm was noted on nasopharyngeal examination. Brain magnetic resonance imaging and pure tone audiometry were unremarkable. Based on these findings, a diagnosis of objective tinnitus due to stapedial myoclonus was made. The objective tinnitus spontaneously disappeared within 48 hours of its appearance, but in the following days the patient suffered frequent, brief episodes of objective tinnitus lasting only a few seconds. CONCLUSION: The occurrence of stapedial myoclonus in this patient indicated the presence of an underlying motor unit hyper-excitability. This case suggests that, in some patients, stapedial myoclonus may represent the clinical expression of diffuse motor unit hyper-excitability.

Head and neck in situ carcinoma: survival analysis of the Thuringian cancer registration database.

Head and neck in situ carcinoma is seldom diagnosed. Our knowledge about in situ cancer is limited. This study describes the epidemiology and prognosis of head and neck in situ cancer in Thuringia, Germany. We analyzed the cancer data of the Thuringian cancer registry database from 1996 to 2005. The database contained 3821 patients with primary head and neck cancer. Thirty-four patients (0.88%) had an in situ carcinoma. They were evaluated for patient's characteristics, tumor stage, incidence, treatment and trends in overall survival (OS) and recurrence-free survival (RFS). During 1996-2005, the average annual incidence of head and neck in situ carcinoma was 0.14 per 100,000 persons. Half of the cases were localized in the larynx. The patients were treated by local excision. Six patients (18%) developed a local recurrence. Only one recurrent tumor was diagnosed in early stage (rT1), but the other five tumors in advanced stage (rT3/rT4). The median time to recurrence was 27.43 months. For all 34 patients with in situ carcinoma, the 5-year OS was 84% and the 5-year RFS 60.4%. OS was better for laryngeal in situ cancer than for oral cavity or pharyngeal in situ cancer (p=0.031). The surveillance of patients with head and neck in situ carcinoma after treatment should be performed like in patients with invasive cancer, because nearly one fifth of patients developed a recurrence, predominantly in advanced stage.

Cabergoline reverses cortical hyperexcitability in patients with restless legs syndrome.

OBJECTIVE: To reverse the profile of abnormal intracortical excitability in patients with restless legs syndrome (RLS) by administering the dopaminergic agonist cabergoline. METHODS: The effects of this drug on motor cortex excitability were examined with a range of transcranial magnetic stimulation (TMS) protocols before and after administration of cabergoline over a period of 4 weeks in 14 patients with RLS and in 15 healthy volunteers. Measures of cortical excitability included central motor conduction time; resting and active motor threshold to TMS; duration of the cortical silent period; short latency intracortical inhibition (SICI) and intracortical facilitation using a paired-pulse TMS technique. RESULTS: Short latency intracortical inhibition was significantly reduced in RLS patients compared with the controls and this abnormal profile was reversed by treatment with cabergoline; the other TMS parameters did not differ significantly from the controls and remained unaffected after treatment with cabergoline. Cabergoline had no effect on cortical excitability of the normal subjects. CONCLUSIONS: As dopaminergic drugs are known to increase SICI, our findings suggest that RLS may be caused by a central nervous system dopaminergic dysfunction. This study demonstrates that the cortical hyperexcitability of RLS is reversed by cabergoline, and provides physiological evidence that this dopamine agonist may be a potentially efficacious option for the treatment of RLS.

Transient ischaemic attacks in two cases of internal carotid artery hypoplasia.

Congenital anomalies of the internal carotid arteries (ICA) and cerebral arteries have not been frequently reported. Moreover, in the literature there is no clear association between hypoplastic carotid and cerebral vessel systems and the occurrence of cerebral ischaemia. We report two cases of unilateral hypoplasia of the ICA affecting two young patients suffering from an episode of minor stroke and from recurrent transient ischaemic attacks, respectively. Congenital variations in the configuration and size of the carotid and cerebral arteries should not always be considered benign conditions and may predispose to cerebral ischaemia in young adults.