An Unusual Cause of Dementia: Essential Diagnostic Elements of Corticobasal Degeneration—A Case Report and Review of the Literature

Corticobasal degeneration (CBD) is an uncommon, sporadic, neurodegenerative disorder of mid- to late-adult life. We describe a further example of the pathologic heterogeneity of this condition. A 71-year-old woman initially presented dysarthria, clumsiness, progressive asymmetric bradykinesia, and rigidity in left arm. Rigidity gradually involved ipsilateral leg; postural instability with falls, blepharospasm, and dysphagia subsequently developed. She has been previously diagnosed as unresponsive Parkinson's Disease. At our clinical examination, she presented left upper-arm-fixed-dystonia, spasticity in left lower limb and pyramidal signs (Babinski and Hoffmann). Brain MRI showed asymmetric cortical atrophy in the right frontotemporal cortex. Neuropsychological examination showed an impairment in visuospatial functioning, frontal-executive dysfunction, and hemineglect. This case demonstrates that association of asymmetrical focal cortical and subcortical features remains the clinical hallmark of this condition. There are no absolute markers for the clinical diagnosis that is complicated by the variability of presentation involving also cognitive symptoms that are reviewed in the paper. Despite the difficulty of diagnosing CBD, somatosensory evoked potentials, motor evoked potentials, long latency reflexes, and correlations between results on electroencephalography (EEG) and electromyography (EMG) provide further support for a CBD diagnosis. These techniques are also used to identify neurophysiological correlates of the neurological signs of the disease

Reflecting on mirror mechanisms:motor resonance effects during action observation only present with low-intensity transcranial magnetic stimulation

Transcranial magnetic stimulation (TMS) studies indicate that the observation of other people's actions influences the excitability of the observer's motor system. Motor evoked potential (MEP) amplitudes typically increase in muscles which would be active during the execution of the observed action. This 'motor resonance' effect is thought to result from activity in mirror neuron regions, which enhance the excitability of the primary motor cortex (M1) via cortico-cortical pathways. The importance of TMS intensity has not yet been recognised in this area of research. Low-intensity TMS predominately activates corticospinal neurons indirectly, whereas high-intensity TMS can directly activate corticospinal axons. This indicates that motor resonance effects should be more prominent when using low-intensity TMS. A related issue is that TMS is typically applied over a single optimal scalp position (OSP) to simultaneously elicit MEPs from several muscles. Whether this confounds results, due to differences in the manner that TMS activates spatially separate cortical representations, has not yet been explored. In the current study, MEP amplitudes, resulting from single-pulse TMS applied over M1, were recorded from the first dorsal interosseous (FDI) and abductor digiti minimi (ADM) muscles during the observation of simple finger abductions. We tested if the TMS intensity (110% vs. 130% resting motor threshold) or stimulating position (FDI-OSP vs. ADM-OSP) influenced the magnitude of the motor resonance effects. Results showed that the MEP facilitation recorded in the FDI muscle during the observation of index-finger abductions was only detected using low-intensity TMS. In contrast, changes in the OSP had a negligible effect on the presence of motor resonance effects in either the FDI or ADM muscles. These findings support the hypothesis that MN activity enhances M1 excitability via cortico-cortical pathways and highlight a methodological framework by which the neural underpinnings of action observation can be further explored. © 2013 Loporto et al

Muscles in “Concert”: Study of Primary Motor Cortex Upper Limb Functional Topography

BACKGROUND: Previous studies with Transcranial Magnetic Stimulation (TMS) have focused on the cortical representation of limited group of muscles. No attempts have been carried out so far to get simultaneous recordings from hand, forearm and arm with TMS in order to disentangle a 'functional' map providing information on the rules orchestrating muscle coupling and overlap. The aim of the present study is to disentangle functional associations between 12 upper limb muscles using two measures: cortical overlapping and cortical covariation of each pair of muscles. Interhemispheric differences and the influence of posture were evaluated as well. METHODOLOGY/PRINCIPAL FINDINGS: TMS mapping studies of 12 muscles belonging to hand, forearm and arm were performed. Findings demonstrate significant differences between the 66 pairs of muscles in terms of cortical overlapping: extremely high for hand-forearm muscles and very low for arm vs hand/forearm muscles. When right and left hemispheres were compared, overlapping between all possible pairs of muscles in the left hemisphere (62.5%) was significantly higher than in the right one (53.5% ). The arm/hand posture influenced both measures of cortical association, the effect of Position being significant [p = .021] on overlapping, resulting in 59.5% with prone vs 53.2% with supine hand, but only for pairs of muscles belonging to hand and forearm, while no changes occurred in the overlapping of proximal muscles with those of more distal districts. CONCLUSIONS/SIGNIFICANCE: Larger overlapping in the left hemisphere could be related to its lifetime higher training of all twelve muscles studied with respect to the right hemisphere, resulting in larger intra-cortical connectivity within primary motor cortex. Altogether, findings with prone hand might be ascribed to mechanisms facilitating coupling of muscles for object grasping and lifting -with more proximal involvement for joint stabilization- compared to supine hand facilitating actions like catching. TMS multiple-muscle mapping studies permit a better understanding of motor control and 'plastic' reorganization of motor system

Sensory-motor interaction in primary hand cortical areas: A magnetoencephalography assessment

Movement control requires continuous and reciprocal exchange of information between activities of motor areas involved in the task program execution and those elaborating proprioceptive sensory information. Our aim was to investigate the sensorimotor interactions in the region dedicated to hand control in healthy humans, focusing onto primary sensory and motor cortices, by selecting the time window at very early latencies. Through magnetoencephalographic recordings, we obtained a simultaneous assessment of sensory cortex activity modulation due to movement and of motor cortex activity modulation due to sensory stimulation, by eliciting a galvanic stimulation to the nerve (the median nerve) innervating a muscle (the opponens pollicis), at rest or during voluntary contraction. The primary sensory and motor cortices activities were investigated respectively through excitability in response to sensory stimulation and the cortico-muscular coherence. The task was performed bilaterally. A clear reduction of the cortico-muscular coherence was found in the short time window following stimuli (between around 150-450 ms). In the same time period, the motor control of isometric contraction was preserved. This could suggest that cortical component of voluntary movement control was transiently mediated by neuronal firing rate tuning more than by cortico-muscular synchronization. In addition to the known primary sensory cortex inhibition due to movement, a more evident reduction was found for the component known to include a contribution from primary motor areas. Gating effects were lower in the dominant left hemisphere, suggesting that sensorimotor areas dominant for hand control benefit of narrowing down gating effects. \ua9 2006 IBRO. Published by Elsevier Ltd

High frequency repetitive transcranial magnetic stimulation decreases cerebral vasomotor reactivity

Objective: Repetitive Transcranial Magnetic Stimulation (rTMS) has been recently employed as a therapeutic strategy for stroke, although its effects on cerebral hemodynamics has been poorly investigated. This study aims to examine the impact of high frequency rTMS on cerebral vasomotor reactivity (VMR). Methods: Twenty-nine healthy subjects were randomly assigned to real (19) or sham 17-Hz rTMS, applied on primary motor cortex (M1) of the dominant hemisphere. All subjects underwent Transcranial Doppler of the middle cerebral arteries to evaluate mean flow velocity and VMR before (T0) and within 10 min (T1) following rTMS. Four subjects underwent further VMR evaluations at 2 (T2), 5 (T3) and 24 h (T4) after rTMS. As a control condition, 10 subjects underwent real (5) or sham rTMS on calcarine cortex. In addition, five acute stroke patients underwent five daily rTMS sessions on the affected hemisphere mimicking a therapeutic trial. Results: Following real rTMS on M1 (p = 0.002) and calcarine cortex (p < 0.001) VMR decreased with respect to T0 in both hemispheres, while no change was observed after sham rTMS (p > 0.6). VMR tended to remain lower than T0 until T3. Cerebral VMR decreased independently of the stimulated side also in the patients' group. Conclusions: High frequency rTMS reduces cerebral VMR, possibly as a secondary effect on autonomic control of cerebral hemodynamics. Significance: The effect of rTMS on cerebral hemodynamics should be carefully considered before proceeding toward a therapeutic application in stroke patients. © 2009 International Federation of Clinical Neurophysiology

Acute modulation of brain connectivity in Parkinson disease after automatic mechanical peripheral stimulation: A pilot study

Objective The present study shows the results of a double-blind sham-controlled pilot trial to test whether measurable stimulus-specific functional connectivity changes exist after Automatic Mechanical Peripheral Stimulation (AMPS) in patients with idiopathic Parkinson Disease. Methods Eleven patients (6 women and 5 men) with idiopathic Parkinson Disease underwent brain fMRI immediately before and after sham or effective AMPS. Resting state Functional Connectivity (RSFC) was assessed using the seed-ROI based analysis. Seed ROIs were positioned on basal ganglia, on primary sensory-motor cortices, on the supplementary motor areas and on the cerebellum. Individual differences for pre-and post-effective AMPS and pre-and post-sham condition were obtained and first entered in respective one-sample ttest analyses, to evaluate the mean effect of condition. Results Effective AMPS, but not sham stimulation, induced increase of RSFC of the sensory motor cortex, nucleus striatum and cerebellum. Secondly, individual differences for both conditions were entered into paired group t-Test analysis to rule out sub-Threshold effects of sham stimulation, which showed stronger connectivity of the striatum nucleus with the right lateral occipital cortex and the cuneal cortex (max Z score 3.12) and with the right anterior temporal lobe (max Z score 3.42) and of the cerebellum with the right lateral occipital cortex and the right cerebellar cortex (max Z score 3.79). Conclusions Our results suggest that effective AMPS acutely increases RSFC of brain regions involved in visuo-spatial and sensory-motor integration. Classification of Evidence This study provides Class II evidence that automatic mechanical peripheral stimulation is effective inmodulating brain functional connectivity of patients with Parkinson Disease at rest

Perceptive rehabilitation improves postural control in patients with Parkinson\u2019s disease: a single-blind, randomized controlled trial

Recent studies aimed to evaluate the potential effects of perceptive rehabilitation in Parkinson Disease reporting promising preliminary results for postural balance and pain symptoms. To date, no randomized controlled trial was carried out to compare the effects of perceptive rehabilitation and conventional treatment in patients with Parkinson Disease. AIM: To evaluate whether a perceptive rehabilitation treatment could be more effective than a conventional physical therapy program in improving postural control and gait pattern in patients with Parkinson Disease. DESIGN: Single blind, randomized controlled trial. SETTING: Department of Physical and Rehabilitation Medicine of a University Hospital. POPULATION: Twenty outpatients affected by idiopathic Parkinson Disease at Hoehn and Yahr stage 64 3. METHODS: Recruited patients were divided into two groups: the first one underwent individual treatment with Surfaces for Perceptive Rehabilitation (Su-Per), consisting of rigid wood surfaces supporting deformable latex cones of various dimensions, and the second one received conventional group physical therapy treatment. Each patient underwent a training program consisting of ten, 45-minute sessions, three days a week for 4 consecutive weeks. Each subject was evaluated before treatment, immediately after treatment and at one month of follow-up, by an optoelectronic stereophotogrammetric system for gait and posture analysis, and by a computerized platform for stabilometric assessment. RESULTS: Kyphosis angle decreased after ten sessions of perceptive rehabilitation, thus showing a substantial difference with respect to the control group. No significant differences were found as for gait parameters (cadence, gait speed and stride length) within Su-Per group and between groups. Parameters of static and dynamic evaluation on stabilometric platform failed to demonstrate any statistically relevant difference both within-groups and between-groups. CONCLUSIONS: Perceptive training may help patients affected by Parkinson Disease into restoring a correct midline perception and, in turn, to improve postural control. CLINICAL REHABILITATION IMPACT: Perceptive surfaces represent an alternative to conventional rehabilitation of postural disorders in Parkinson Disease. Further studies are needed to determine if the association of perceptive treatment and active motor training would be useful in improving also gait dexterity