Antonio Fiaschi

Motor disinhibition in affected and unaffected hemisphere in the early period of recovery after stroke.

OBJECTIVES To investigate motor disinhibition in affected and unaffected motor areas in the acute stage after stroke and during the early period of recovery. METHODS Fifteen patients with moderate to severe hemiparesis after acute unilateral stroke were compared with 10 healthy age-matched controls. We used paired transcranial magnetic stimulation to study intracortical inhibition and facilitation from the thenar eminence muscles on both sides. F-wave from the median nerve on both sides were recorded. The recordings were performed 5-7 days (T1) and 30 days after stroke. RESULTS In 10 patients who showed the presence of reliable motor evoked potentials on the affected side, intracortical inhibition was significantly reduced. On the unaffected side intracortical inhibition (ICI) was significantly reduced in all patients. Patients who presented significant motor recovery after 30 days showed persistence of abnormal disinhibition in the affected hemisphere but a return to normal ICI in the unaffected hemisphere. Patients with poor motor recovery showed persistence of abnormal disinhibition on both sides. No significant changes were observed in F-wave amplitude. CONCLUSIONS Motor disinhibition occurs on both sides after stroke in all acute stage patients. Changes in motor disinhibition on unaffected side also are related to motor recovery.

Pain as a nonmotor symptom of Parkinson disease: evidence from a case-control study

OBJECTIVE To determine whether pain is more frequent among people with Parkinson disease (PD) than among age-matched controls. DESIGN Case-control study. PATIENTS AND METHODS Logistic regression models taking into account type of pain, time between pain and PD onset, and possible confounders were used to compare 402 PD patients with 317 age-matched healthy control subjects. RESULTS The overall frequency of pain was significantly greater in PD patients than in controls (281 [69.9%] vs 199 [62.8%]; P = .04), mainly because the healthy control group lacked dystonic pain. Conversely, the frequency of nondystonic pain was similar among PD patients and controls (267 [66.4%] vs 199 [62.8%]; P = .28). Nevertheless, we observed a significant association between PD and nondystonic pain, beginning after the onset of parkinsonian symptoms (odds ratio, 2.1; 95% confidence interval, 1.4-2.9). Cramping and central neuropathic pain were more frequent among PD patients than controls. About one-quarter of patients who experienced pain reported pain onset before starting antiparkinsonian therapy. CONCLUSION These data support the hypothesis that pain begins at clinical onset of PD or thereafter as a nonmotor feature of PD.

Pain and motor complications in Parkinson's disease

Aims: To study the association of pain with motor complications in 117 patients with Parkinson’s disease. Methods: Patients were asked to refer any pain they experienced at the time of study and lasting since at least 2 months. Basic parkinsonian signs and motor complications (including motor fluctuations and dyskinesia) were assessed and Unified Parkinson’s Disease Rating Scale (UPDRS) motor score part III (during on) and part IV were calculated. Information on age, sex, duration of disease, use of dopamine agonists and levodopa, years of levodopa treatment and current levodopa dosage, medical conditions possibly associated with pain, and depression were collected. Single and multiple explanatory variable logistic regression models were used to check the association of pain with the investigated variables. Results: Pain was described by 47 patients (40%) and could be classified into dystonic (n.19) and non dystonic pain (n.16); in 12 patients both types coexisted. Multiple explanatory variable logistic regression models indicated a significant association of pain with motor complications (adjusted OR, 5.7; 95% CI, 2 to 16.5; p = 0.001). No association was found between pain, dystonic or non dystonic, and the other investigated variables including medical conditions known to be associated to pain in the general population. There was a significant correlation (r = 0.31, p<0.05) between severity of pain (measured on a Visual Analogue Scale) and severity of motor complications (UPDRS part IV). Conclusions: Pain may be a representative feature of Parkinson’s disease frequently associated with motor complications. The association is independent of a number of potentially relevant demographic and clinical variables.

Role of the somatosensory system in primary dystonia

The pathophysiology of dystonia is still not fully understood, but it is widely held that a dysfunction of the corticostriatal–thalamocortical motor circuits plays a major role in the pathophysiology of this syndrome. Although the most dramatic symptoms in dystonia seem to be motor in nature, marked somatosensory perceptual deficits are also present in this disease. In addition, several lines of evidence, including neurophysiological, neuroimaging and experimental findings, suggest that both motor and somatosensory functions may be defective in dystonia. Consequently, abnormal processing of the somatosensory input in the central nervous system may lead to inefficient sensorimotor integration, thus contributing substantially to the generation of dystonic movements. Whether somatosensory abnormalities are capable of triggering dystonia is an issue warranting further study. Although it seems unlikely that abnormal somatosensory input is the only drive to dystonia, it might be more correlated to the development of focal hand than generalized dystonia because local somesthetic factors are more selectively involved in the former than in the latter where, instead it seems to be a widespread deficit in processing sensory stimuli of different modality. Because basal ganglia and motor areas are heavily connected not only with somatosensory areas, but also with visual and acoustic areas, it is possible that abnormalities of other sensory modalities, such as visual and acoustic, may also be implicated in the pathophysiology of more severe forms of primary dystonia. Further studies have to be addressed to the assessment of the role of sensory modalities and their interaction on the pathophysiology of different forms of primary dystonia.

Effect of Balance Training on Postural Instability in Patients With Idiopathic Parkinson’s Disease

Background. Postural instability (PI) is a disabling sign of Parkinson’s disease (PD) not easily amenable to treatment with medication. Objective. To evaluate the effects of balance training on PI in patients with PD. Methods. A total of 64 patients with PI were randomly assigned to the experimental group (n = 33) for balance training or to the control group (n = 31) for general physical exercises. Each patient received 21 treatment sessions of 50 minutes each. Patients were evaluated by a blinded rater before and after treatment as well as 1 month posttreatment using the Berg Balance Scale (BBS), Activities-Specific Balance Confidence Scale (ABC), postural transfer test, self-destabilization of the center of foot pressure test, number of falls, Unified Parkinson’s Disease Rating Scale (UPDRS), modified Hoehn and Yahr (H&Y) Staging Scale, and Geriatric Depression Scale (GDS). Results .At the end of treatment, the experimental group showed significant improvements in all outcome measures, except for the UPDRS and the H&Y scale. Improvement was maintained at the 1-month follow-up in all outcome measures except for the GDS. No significant changes in performance were observed in the control group. Conclusions. A program of balance training can improve PI in patients with PD.

Modulation of motor cortex excitability in the left hemisphere during action observation: a single- and paired-pulse transcranial magnetic stimulation study of self- and non-self-action observation

Motor system excitability was tested by transcranial magnetic stimulation (TMS), and F-wave and H-reflex evaluation in different action observation tasks. Our aim was to investigate the effects produced by self- versus non-self-hand movement observation (MO). No significant differences were found between the self- and non-self-conditions. Movement observation significantly modulated motor cortex excitability, producing an increase in the amplitude of motor evoked potentials (MEPs) with a single magnetic pulse and a reduction in intracortical inhibition (ICI) with paired-pulse stimulation. No significant changes were found in motor cortex excitability during the observation of geometric objects. Motor imagery produced similar effects to those of action observation; no significant differences in modulation of motor system excitability between motor imagery and action observation were found in those muscles involved in actual motor execution. No significant effect on spinal excitability was found in any of the test conditions.

Learning potentiates neurophysiological and behavioral placebo analgesic responses.

Abstract Expectation and conditioning are supposed to be the two main psychological mechanisms for inducing a placebo response. Here, we further investigate the effects of both expectation, which was induced by verbal suggestion alone, and conditioning at the level of N1 and N2–P2 components of CO2 laser‐evoked potentials (LEPs) and subjective pain reports. Forty‐four healthy volunteers were pseudorandomly assigned to one of three experimental groups: Group 1 was tested with verbal suggestion alone, Group 2 was tested with a conditioning procedure, whereby the intensity of painful stimulation was reduced surreptitiously, so as to make the volunteers believe that the treatment was effective, Group 3 was a control group that allowed us to rule out phenomena of sensitization and/or habituation. Pain perception was assessed according to a Numerical Rating Scale (NRS) ranging from 0 = no pain sensation to 10 = maximum imaginable pain. Both verbal suggestions (Group 1) and conditioning (Group 2) modified the N2–P2 complex, but not the N1 component of LEPs. However, the suggestion‐induced LEP changes occurred without subjective perception of pain decrease. Conversely, the N2–P2 amplitude changes that were induced by the conditioning procedure were associated with the subjective perception of pain reduction. Compared to natural history, conditioning produced more robust reductions of LEP amplitudes than verbal suggestions alone. Overall, these findings indicate that prior positive experience plays a key role in maximizing both behavioral and neurophysiological placebo responses, emphasizing that the placebo effect is a learning phenomenon which affects the early central nociceptive processing.

Modulation of cortical oscillatory activities induced by varying single-pulse transcranial magnetic stimulation intensity over the left primary motor area: a combined EEG and TMS study.

Combined transcranial magnetic stimulation/electroencephalography (TMS/EEG) was used to study the activation and interaction of cortical regions to a variety of focused sub- and suprathreshold magnetic pulses over the left primary motor cortex (M1) in ten healthy subjects. Five single-pulse TMS conditions were performed based on the individual resting motor threshold (RMT): (1) 80%; (2) 100%; (3) 120%; (4) 130%; and (5) sham. Simple self-paced movements of the right first finger were also executed. We evaluated the reactions to magnetic stimulation and movement conditions using event-related power and event-related coherence transformations of alpha and beta rhythms. Event-related power reflected regional oscillatory activity of neural assemblies, while event-related coherence reflected the inter-regional functional coupling of oscillatory neural activity. The event-related power transformation revealed that the magnetic pulse modulated cortical oscillations within the first half second for both frequency ranges. For the alpha rhythm, threshold TMS induced a small decrease in the amplitude of EEG oscillations over the stimulation site, while for both rhythms, a progressive synchronization was observed as the intensity of TMS was increased in both hemispheres. Movement onset produced a greater bilateral decrease of power compared with the effects of a magnetic pulse. The event-related coherence revealed that TMS enhanced the electrode connectivity of both hemispheres. Additionally, it was more enhanced within the first 500 ms following stimulation and was seen only for the alpha frequency rhythm. The increase of functional connectivity between cortical areas was minor for magnetic stimulation conditions compared with that for finger movements. The single-pulse TMS over M1 partially modulated the motor cortex generators of oscillatory activity, while a simple active self-paced movement of the right first finger induced greater cortex activation and coupling between cortical regions. We propose that finger movements impose higher functional demands on the motor system compared to artificial magnetic stimulation. These findings are consistent with the possibility that the human motor system may be based on network-like oscillatory cortical activity and might be modulated by brief electromagnetic sub- and suprathreshold pulses applied to M1, suggesting a phenomenon of resetting.

Reversible changes of motor cortical outputs following immobilization of the upper limb

We mapped the cortical representations of the abductor pollicis brevis, flexor carpi radialis, biceps and deltoid muscles in six subjects with unilateral wrist fractures, immediately after the removal of the splint. This was repeated 1 month later in three out of the six subjects. Duration of immobilization was 1 month. Muscle maps were obtained by delivering four focal magnetic pulses for each scalp position (1 cm apart with reference to Cz) over the contralateral hemisphere. Motor evoked potentials (MEPs) were averaged off-line and expressed as a percentage of the motor action potential evoked by supramaximal peripheral nerve stimulation. Volume, area and threshold of the motor maps showed no significant hemispheric differences within each muscle in 10 control subjects. In the first recording session the volume of each immobilized muscle was distinctly higher when compared to that of controls in terms of absolute value and side-to-side ratio. This finding disappeared 1 month later. Moreover, MEP amplitude difference recorded from hand muscle could be reversed during a small tonic voluntary contraction. Immobilization had no significant effect on the threshold for activation of the target muscles and on the area of the motor map. The increase in MEP amplitudes occurred without changes in spinal excitability as tested by the F wave. These findings suggest that immobilization of the upper limb induces a reversible enhancement of the excitability of structures along the corticomotoneuronal pathway. Sustained restriction of volitional movements and reduction in somatic sensory inputs might promote this functional modulation of the motor system.

Motor Cortical Disinhibition During Early and Late Recovery After Stroke

Background. Functional neuroimaging studies show adaptive changes in areas adjacent and distant from the stroke. This longitudinal study assessed whether changes in cortical excitability in affected and unaffected motor areas after acute stroke correlates with functional and motor recovery. Methods. We studied 13 patients with moderate to severe hemiparesis 5 to 7 days (T1), 30 days (T2), and 90 days (T3) after acute unilateral stroke, as well as 10 healthy controls. We used paired-pulse transcranial magnetic stimulation to study intracortical inhibition and facilitation, recording from the bilateral thenar eminences. F waves were also recorded. Results. At T1, all patients showed significantly reduced intracortical inhibition in the unaffected hemisphere. At T2, in patients whose motor function recovered, intracortical inhibition in the unaffected hemisphere returned to normal. In patients with poor clinical motor recovery, abnormal disinhibition persisted in both hemispheres. At T3, in patients whose motor function progressively recovered, the abnormal disinhibition in the unaffected hemisphere decreased further, whereas in patients whose motor function remained poor, abnormal inhibition in the unaffected hemisphere persisted. No modification of F-wave latency and amplitude were found in patients and controls. Conclusions. During early days after stroke, motor cortical disinhibition involves both cerebral hemispheres. Longitudinal changes in motor disinhibition of the unaffected hemisphere may reflect the degree of clinical motor recovery.