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Intracranial hematomas (IHs) occur commonly after severe traumatic brain injury, but their effects on outcomes in patients with prolonged disorders of consciousness (DoC) following coma (i.e., unresponsive wakefulness syndrome and minimally conscious state) are unknown.In this multicenter longitudinal study, we compared clinical outcomes and serum neurofilament light chain (NFL) levels of 52 patients with traumatic DoC with (n = 35) and without (n = 17) IH in the acute phase. Patients were evaluated with the Coma Recovery Scale-Revised (CRS-R) at enrollment (1-3 months post-injury) and with the CRS-R, extended Glasgow Outcome Scale (GOSE), and Functional Independence Measure (FIM) at 6 months post-injury. At the same timepoints, serum NFL levels were compared between patients with and without IHs and with those of 52 sex- and age-matched healthy controls.Patients with and without IH did not differ in terms of DoC or CRS-R scores at admission, or clinical outcomes (death, unresponsive wakefulness syndrome, minimally conscious state, or emergence from minimally conscious state) or CRS-R, GOSE, or FIM scores 6 months post-injury. NFL levels were significantly higher in patients than in controls at admission and 6 months post-injury (both p 0.0001), but they did not differ between patients with and without IH.This study showed that IHs do not affect clinical outcomes or markers of axonal degeneration in patients with traumatic DoC.

PurposeA potential involvement of thyrotropic axis in influencing the state of consciousness could be hypothesized. We aimed at investigating thyroid function tests as predictors of disorders of consciousness (DoC) and relating recovery in a large cohort of patients with DoC secondary to acquired brain injury (ABI).MethodsThis retrospective, multicenter, cohort study included 151 patients with DoC following ABI, consecutively admitted for a 6-month neurorehabilitation program. Data on etiology of brain injury, evolution of DoC, disability and rehabilitation assessments, and death during rehabilitation were collected at baseline and on discharge. Thyroid function tests (serum TSH, fT4 and fT3 levels) were assessed on admission in all patients and at final discharge in 50 patients.ResultsLower baseline TSH levels and greater TSH increments (ΔTSH) after neurorehabilitation predicted a favorable change in DoC independent of age, sex, BMI, etiology of brain injury and initial DoC subtype (TSH: OR=0.712, CI 95% 0.533-0.951, p=0.01; ΔTSH: OR=2.878, CI 95% 1.147-7.223, p=0.02). On the other hand, neither fT4 nor fT3 or their variations appeared to play any role on DoC changes after 6-months inpatient neurorehabilitation. A lower magnitude of ΔfT4 acted as a strong predictor of improved functional disability level (β=0.655, p=0.002) and cognitive functions (β=-0.671, p=0.003), implying that smaller changes in fT4 were associated with higher outcomes.ConclusionsSerum TSH levels assessed in the subacute post-ABI phase and its variation during neurorehabilitation could represent a potential biomarker of DoC evolution, while variations in fT4 levels seem to be associated with rehabilitation and cognitive functions. Further studies are needed to investigate the mechanisms underlying these associations.

Growing evidence suggests that pathophysiological mechanisms leading to neurodegeneration and neuronal loss take place during the chronic phase of a severe traumatic brain injury (TBI). In this study we evaluated a well-established marker of brain injury, the neuron-specific enolase (NSE), in the serum of 51 patients with severe TBI (86% males, mean age 33.8 ± 11.1 years). All patients' samples were available from a previous study and the mean time between TBI and blood sample collection was 23.2 ± 31.5 months (28 patients were evaluated within 12 months of TBI and 23 patients were evaluated ≥12 months after TBI). Patients' NSE levels were compared with those obtained from 30 age and sex-matched healthy controls (87% males, 33.7 ± 11.3 years). We found that NSE levels were significantly lower in patients (median 3.2 ng/mL; 25th, 75th percentile 2.5, 5.1) than in healthy controls (median 4.1 ng/mL; 25th, 75th percentile 3.1, 7.5) (

Disorders of consciousness (DOCs), i.e., coma, vegetative state, and minimally conscious state are the consequences of a severe brain injury that disrupts the brain ability to generate consciousness. Recovery from DOCs requires functional and structural changes in the brain. The sites where these plastic changes take place vary according to the pathophysiology of the DOC. The ascending reticular activating system of the brainstem and its complex connections with the thalamus and cortex are involved in the pathophysiology of coma. Subcortical structures, such as the striatum and globus pallidus, together with thalamocortical and corticothalamic projections, the basal forebrain, and several networks among different cortical areas are probably involved in vegetative and minimally conscious states. Some mechanisms of plasticity that allegedly operate in each of these sites to promote recovery of consciousness will be discussed in this chapter. While some mechanisms of plasticity work at a local level, others produce functional changes in complex neuronal networks, for example by entraining neuronal oscillations. The specific mechanisms of brain plasticity represent potential targets for future treatments aiming to restore consciousness in patients with severe DOCs.

The diagnostic framework and the therapeutic management of patients with adult dystonia can represent a challenge for clinical neurologists. The objective of the present paper is to delineate diagnostic and therapeutic recommendations for dystonia provided by a panel of Italian experts afferent to the Italian Society of Neurology, the Italian Academy for the Study of Parkinson's Disease and Movement Disorders, and the Italian Network on Botulinum Toxin. We first discuss the clinical approach and the instrumental assessment useful for diagnostic purpose. Then, we analyze the pharmacological, surgical, and rehabilitative therapeutic options for adult dystonia. Finally, we propose a hospital-territory network model for adult dystonia management.

Background and purpose. Patients with prolonged disorders of consciousness (pDoC) have a high mortality rate due to medical complications. Since an accurate prognosis is essential for decision-making on patients’ management, we analysed data from an international multicentre prospective cohort study to evaluate two-year mortality rate and bedside predictors of mortality. Methods. We enrolled adult patients in prolonged vegetative state/unresponsive wakefulness syndrome (VS/UWS) or minimally conscious state (MCS) after traumatic and non-traumatic brain injury within 3 months post-injury. At enrolment we collected demographic (age; sex), anamnestic (etiology; time post-injury), clinical (Coma Recovery Scale Revised, CRS-R; Disability Rating Scale; Nociception Coma Scale-Revised) and neurophysiologic (EEG; somatosensory evoked and event-related potentials) data. Patients were followed-up to gather data on mortality up to 24 months post- injury. Results. Among 143 traumatic (n=55) and non-traumatic (n=88) patients (VS/UWS=68, 19 females; MCS=75, 22 females), 41 (28.7%) died within 24 months post-injury. Mortality rate was higher in VS/UWS (42.6%) than in MCS (16%; p Conclusions. This study demonstrated that a feasible multimodal assessment in the post-acute phase can help clinicians to identify patients with pDoC at higher risk of mortality within 24 months after brain injury. This evidence can help clinicians and patients’ families to navigate the complex clinical decision-making process and promote an international standardization of prognostic procedures for patients with pDoC.

INTRODUCTION/AIMS Neurophysiological patterns in patients with foodborne botulism are rarely described after the acute phase. We report data from a large Italian outbreak of botulism, with patients evaluated at different timepoints after poisoning. METHODS Eighteen male patients (mean age 47 ± 8.4 y) underwent 22 clinical and neurophysiological evaluations (4 patients were re-evaluated). The resting compound muscle action potential (CMAP) amplitude, postexercise CMAP amplitude, CMAP change after high-frequency (50 Hz) repetitive nerve stimulation (HFRNS), and motor unit action potentials (MUAPs) were assessed in the acute (4-8 days after poisoning; 5 patients), early post-acute (32-39 days after poisoning; 5 patients), and late post-acute (66-80 days after poisoning; 12 patients) phases. RESULTS In the acute, early post-acute, and late post-acute phases, respectively, reduced CMAP amplitudes were found in 100%, 20%, and 17% of patients; abnormal postexercise CMAP facilitation was observed in 100%, 40%, and 0% of patients; and pathological incremental responses to HFRNS were found in 80%, 50%, and 8% of patients. Baseline CMAP amplitudes, postexercise CMAP facilitation, and CMAP increases in response to HFRNS differed significantly between the acute and post-acute phases. Small MUAPs were found in 100% of patients in the acute and early post-acute phases and in 50% of patients in the late post-acute phase. DISCUSSION The neurophysiological findings of foodborne botulism vary considerably according to the evaluation time point. In the post-acute phase, different neurophysiological techniques must be applied to support a diagnosis of botulism.

Objective To prospectively investigate relationships of cortical somatosensory evoked potential (SEP) amplitudes with consciousness recovery and disability in the year following brain injury in patients with vegetative state/unresponsive wakefulness syndrome (VS/UWS). Methods SEPs of 42 patients with VS/UWS were recorded 51.7 ± 23.3 days post-injury. N20–P25 amplitudes were compared between patients with and without consciousness recovery at 6 months and 1 year post-injury. Results SEPs were present in 21 patients and bilaterally absent in 21 patients. N20–P25 amplitudes were significantly higher in patients who recovered consciousness than in those who died or did not recover consciousness at 6 months (median, 4.6 vs. 1.9 μV; P = 0.004) and 1 year (median, 4.6 vs. 2.1 μV; P = 0.02) after injury. The lowest N20–P25 amplitude in a patient who recovered consciousness was 2.15 μV. N20–P25 amplitudes correlated significantly with Coma Recovery Scale-Revised and Disability Rating Scale scores at 6 months and 1 year post-injury (both P Conclusions In patients with VS/UWS, SEP amplitudes are related to consciousness recovery and disability at 6 months and 1 year post-injury. Significance The evaluation of SEP amplitudes can help to refine prognoses for patients with VS/UWS.

Little is known about plastic changes occurring in the brains of patients with severe disorders of consciousness (DOCs) caused by acute brain injuries at rest and during rehabilitative treatment. Brain-derived neurotrophic factor (BDNF) is a neurotrophin involved in neurogenesis and synaptic plasticity whose production is powerfully modulated by physical exercise. In this study, we compared serum BDNF levels in 18 patients with unresponsive wakefulness syndrome (UWS) and in a minimally conscious state (MCS) with those in 16 sex- and age-matched healthy controls. In 12 patients, serum BDNF levels before and after verticalization with ErigoPro robot-assisted lower-limb training were compared. Serum BDNF levels were significantly lower in patients (median, 1141 pg/ml; 25th and 75th percentiles, 1016 and 1704 pg/ml) than in controls (median, 2450 pg/ml; 25th and 75th percentiles, 2100 and 2875 pg/ml; p<0.001). BDNF levels measured before and after verticalization with robot-assisted lower-limb training did not change (p=0.5). Moreover, BDNF levels did not differ between patients with UWS and MCS (p=0.2), or between patients with traumatic and nontraumatic brain injuries (p=0.6). BDNF level correlated positively with the time since brain injury (p=0.025). In conclusion, serum BDNF levels are reduced in patients with UWS and MCS and cannot be improved by verticalization associated with passive lower-limb training. Additional studies are needed to better understand the mechanisms underlying BDNF reduction in patients with DOCs and to determine the best rehabilitative strategies to promote restorative plastic changes in these patients.

The aim of this study was to evaluate whether standardized responses to nociceptive pain, assessed with the revised Nociception Coma Scale (NCS-R), were correlated with the outcomes of patients with unresponsive wakefulness syndrome (UWS) 6 months after admission to a rehabilitation department. We recruited 24 consecutive patients with UWS. Patients’ consciousness levels were assessed with the revised Coma Recovery Scale (CRS-R) at admission and 6 months later, and their CRS-R scores were correlated with the NCS-R scores at admission. Ten of the 24 patients with UWS recovered consciousness after 6 months. The NCS-R score at admission was correlated with the CRS-R score at admission (P = 0.02), but not after 6 months (P = 0.6). Patients with and without consciousness improvement after 6 months showed no significant difference in the NCS-R total score and sub-scores at admission (P values > 0.05). In conclusion, the correlation between NCS-R and CRS-R scores at admission suggests that the standardized assessment of pain parallels patients’ levels of consciousness, and may be helpful in the clinical evaluation of patients with UWS. Pain response assessed with the NCS-R was not related to the 6-month outcomes of patients with UWS.

Introduction: Peripheral neuropathy can affect patients with heart failure, though its prevalence is unknown. After heart transplantation, it can influence the postoperative course and quality of life, but screening for neuromuscular disease is not routinely performed. Objective: The aim of this study was to identify the factors associated with neuropathy in a population of patients with heart failure who are candidates for heart transplantation. Study Design: Data regarding patients’ clinical history, including recent hospitalizations, were collected. All patients underwent a complete neurological examination and a neurophysiological protocol including nerve conduction studies and concentric needle electromyography. Results: Thirty-two patients were included in the study, and neuropathy was diagnosed in 10 (31.3%). Neuropathy was associated with the number of admissions ( P = .023; odds ratio [OR]: 1.96) and the total number of days of hospitalization in the year prior to inclusion in the study ( P = .010; OR: 1.03). The majority of hospitalizations occurred in the step-down unit (85%), with acute heart failure the leading cause of admission (42%). Conclusions: This study shows that neuropathy is frequent in patients with advanced heart failure and that hospitalization for cardiac care, also in the absence of intensive care, is a marker of high risk of neurologic damage. These data can help physicians in selecting and managing candidates for transplantation and can guide decisions on the best immunosuppressive regimen or rehabilitation strategy.

The mechanisms involved in secondary brain injury after the acute phase of severe traumatic brain injury (TBI) are largely unknown. Ongoing axonal degeneration, consequent to the initial trauma, may lead to secondary brain injury. To test this hypothesis, we evaluated the cerebrospinal fluid (CSF) level of neurofilament light chain (NF-L), a proposed marker of axonal degeneration, in 10 patients who developed a severe disorder of consciousness after a TBI, including 7 in a minimally conscious state and 3 with unresponsive wakefulness syndrome (time since brain injury, 309 ± 169 days). CSF NF-L level was measured with a commercially available NF-L enzyme-linked immunosorbent assay. CSF NF-L level was very high in all 10 patients, ranging from 2.4- to 60.5-fold the upper normal limit (median value, 4458 pg/mL; range, 695-23,000). Moreover, NF-L level was significantly higher after a severe TBI than in a reference group of 9 patients with probable Alzheimer's disease, a population with elevated levels of CSF NF-L attributed to neuronal degeneration (median value, 1173 pg/mL; range, 670-3643; p 0.01). CSF NF-L level was correlated with time post-TBI (p = 0.04). These results demonstrate prolonged secondary brain injury, suggesting that patients exhibit ongoing axonal degeneration up to 19 months after a severe TBI.

To identify changes in the standard electroencephalograms (EEGs) of patients with unresponsive wakefulness syndrome (UWS) who did or did not recover consciousness 6 months after admission to a rehabilitation department.Prospective cohort study.Unit for severe acquired brain injuries.Consecutive patients with UWS (N=28).Not applicable.EEG amplitude (reduced or normal), dominant frequency (alpha, theta, or delta), and reactivity (absent or present) were scored at admission and 6 months later. The cumulative Amplitude-Frequency-Reactivity score was evaluated. Clinical assessments were made using the Coma Recovery Scale-Revised.Sixteen (57.1%) of the 28 patients with UWS recovered consciousness after 6 months, while 12 patients (42.9%) did not recover consciousness. EEG improvements occurred in 14 patients with consciousness recovery (87.5%) and 2 patients without consciousness recovery (16.7%) only. Improvements in EEG dominant frequency (from the theta to the alpha band or from the delta to the theta band), reappearance of EEG reactivity, and Amplitude-Frequency-Reactivity score increase (P.01) differentiated patients with consciousness improvement from those without consciousness improvement. Six months after admission for rehabilitation, patients with EEG improvements showed higher Coma Recovery Scale-Revised scores than did those without EEG changes (P.01).Most patients who emerge from UWS demonstrate improvement in basic EEG characteristics over time. EEG changes in patients with UWS may aid in the timely recognition of patients transitioning into a minimally conscious state.

Neuropathies may affect heart reinnervation and functional outcome after heart transplantation (HT). In this study, neurological evaluations, standard nerve conduction studies, and electromyography were performed in 32 HT candidates without a previous history of neuromuscular disorder. Ten patients underwent HT and were revaluated 3 months later. We found that before HT 10 (31.3%) patients had sensorimotor polyneuropathy (18.8%) or sensory polyneuropathy (12.5%). After HT, the percentage of patients with a neuromuscular disorder increased to 70%, most of them showing new or worsening neuropathies or neuromyopathies. The most sensitive abnormality that indicated neuromuscular involvement after HT was a reduction of the compound muscle action potential (CMAP) of the deep peroneal nerve. In conclusion, neuromuscular disorders are common in HT candidates, and they further increase in occurrence after HT. A reduction of the deep peroneal nerve CMAP amplitude after HT may help to identify patients who need a more detailed neurophysiological evaluation. The diagnosis of neuromuscular disorders before and after HT may contribute to the development of more accurate therapeutic and rehabilitative strategies for these patients.

Background: Traumatic brain injury (TBI) is a major risk factor for Alzheimer’s disease (AD). Although the mechanisms that lead to AD after a TBI are unclear, we hypothesize that changes in amyloid-β (Aβ) metabolism and abnormal tau phosphorylation are reasonable candidates.Objective: To investigate Aβ and tau dynamics in the chronic phase of TBI.Methods: We evaluated Aβ1-42, total tau (t-tau), and phosphorylated tau (p-tau) levels in the cerebrospinal fluid (CSF) of 15 patients who developed a prolonged disorder of consciousness after a severe TBI (mean time from TBI 271.6 ± 176.5 days).Results: Reduced Aβ1-42 levels (median 258 pg/ml, range 90–833.6) were observed in 14/15 patients (93.3%) with severe post-TBI disorders of consciousness. These CSF analysis data did not correlate with time since TBI or with the patients’ level of consciousness as determined by the Coma Recovery Scale Revised. Normal t-tau levels (median 95.2 pg/ml, range 52–256.9) were found in all patients. Normal p-tau levels (...

Objective: Glioblastoma multiforme (GBM) represents the most common and malignant glioma, accounting for 45%-50% of all gliomas. The median survival time for patients with glioblastoma is only 12-15 months after surgical, chemioterapic and radiotherapic treatment; a correct diagnosis is naturally fundamental to establish a rapid and correct therapy. Non-invasive imaging plays a pivotal role in each phase of the diagnostic workup of patients with suspected for diagnosis. The aim of this case report was to describe the potential clinical impact of 18F-fluorocholine (FCH) PET/CT in the assessment of a cystic GBM mimicking a spontaneous hemorrhage. Methods: a 57 years-old male with intraparenchymal hemorrhage at CT imaging initially in reduction ad serial imaging and suspected right fronto-temporo-parietal lesion at MRI underwent dynamic and static (60' after tracer injection) FCH PET/CT of the brain. Results: FCH PET/CT showed rapid tracer uptake after few second from injection at dynamic acquisition and consequent incremental mild uptake at static imaging after 60 minutes at the level of oval formation in the right cerebral hemisphere characterized by annular and peripheral high metabolic activity. The central region of the lesion was characterized by the absence 18F-FCH uptake most likely due to blood component. The patient underwent surgery for tumor removal; the histopathological examination confirmed the suspect of GBM. Chemo-radiotherapic adjuvant protocol according to Stupp protocol was therefore administrated; to date the patient is alive without any progression disease at 5 months from treatment. Conclusion: In this case report FCH PET/CT represented the final diagnostic technique to confirm the suspicious of a cystic GBM. Our case demonstrated the potential role of 18F-FCH PET/CT for discrimination of higher proliferation area over intraparenchymal hemorrhage, supporting the potential use of this imaging biomarker in surgical or radiosurgical approach. Obviously, further prospective studies are needed to confirm this role and to exactly define possible routinely applications.

Traumatic brain injury (TBI) is a major risk factor for Alzheimer's disease. Recent studies suggest that amyloid-beta (Aβ) deposit can be detected several years after TBI. However, it is unknown whether post-TBI Aβ deposits arise from short-term changes in Aβ metabolism or reflect a long-term sequela. To answer this question, we evaluated the cerebrospinal levels of Aβ several months after a severe TBI. The participants of this study were eight consecutive patients who developed a disorder of consciousness after a TBI, including seven in a minimally conscious state and one with unresponsive wakefulness syndrome (mean age: 35.4±14.2 years, mean time since brain injury 297.9±189.8 days). Cerebrospinal Aβ1-42 peptide was measured using a commercially available Aβ enzyme-linked immunoassay kit. Reduced Aβ1-42 levels were observed in seven of eight (87.5%) patients with severe post-TBI disorders of consciousness, with the magnitude of reduction among these seven patients ranging from 27 to 75.1% of the lower normal limit. These results point to prolonged changes in Aβ metabolism after a TBI and they suggest a potential mechanism of long-term neurotoxicity.

Discrimination between patients in vegetative (VS) and minimally conscious state (MCS) is currently based upon the behavioral gold standard. Behavioral assessment remains equivocal and difficult to interpret as evidence for the presence or absence of consciousness, resulting in possible clinical misdiagnosis in such patients. Application of an operational architectonics (OA) strategy to electroencephalogram (EEG) analysis reveals that absence of consciousness in patients in VS is paralleled by significant impairment in overall EEG operational architecture compared to patients in MCS: neuronal assemblies become smaller, their life span shortened, and they became highly unstable and functionally disconnected (desynchronized). However, in a previous study, patients with different brain damage etiologies were intermixed. Therefore, the goal of the present study was to investigate whether the application of OA methodology to EEG could reliably dissociate patients in VS and MCS independent of brain damage etiology. We conclude that the observed EEG OA structure impairment in patients in VS and partial preservation in patients in MCS is a marker of consciousness/unconsciousness rather than physiological damage. Results of this study may have neuroscientific, clinical, and ethical implications.

Background. Patients in a vegetative state pose problems in diagnosis, prognosis, and treatment. Currently, no prognostic markers predict the chance of recovery, which has serious consequences, especially in end-of-life decision making. Objective. We aimed to assess an objective measurement of prognosis using advanced electroencephalography (EEG). Methods. EEG data (19 channels) were collected in 14 patients who were diagnosed to be persistently vegetative based on repeated clinical evaluations at 3 months following brain damage. EEG structure parameters (amplitude, duration, and variability within quasi-stationary segments, as well as the spatial synchrony between such segments and the strength of this synchrony) were used to predict recovery of consciousness 3 months later. Results. The number and strength of cortical functional connections between EEG segments were higher in patients who recovered consciousness ( P < .05 to P < .001) compared with those who did not recover. Linear regression analysis confirms that EEG structure parameters are capable of predicting ( P = .0025) recovery of consciousness 6 months postinjury, whereas the same analysis failed to significantly predict patient outcome based on aspects of their clinical history alone ( P = .629) or conventional EEG spectrum power ( P = .473). Conclusions. The result of this preliminary study demonstrates that structural strategy of EEG analysis is better suited for providing prognosis of consciousness recovery than existing methods of clinical assessment and of conventional EEG. Our results may be a starting point for developing reliable prognosticators in patients who are in a vegetative state, with the potential to improve their day-to-day management, quality of life, and access to early interventions.

The value of resting electroencephalogram (EEG) in revealing neural constitutes of consciousness (NCC) was examined. We quantified the dynamic repertoire, duration and oscillatory type of EEG microstates in eyes-closed rest in relation to the degree of expression of clinical self-consciousness. For NCC a model was suggested that contrasted normal, severely disturbed state of consciousness and state without consciousness. Patients with disorders of consciousness were used. Results suggested that the repertoire, duration and oscillatory type of EEG microstates in resting condition quantitatively related to the level of consciousness expression in brain-damaged patients and healthy-conscious subjects. Specifically, results demonstrated that (a) decreased number of EEG microstate types was associated with altered states of consciousness, (b) unawareness was associated with the lack of diversity in EEG alpha-rhythmic microstates, and (c) the probability for the occurrence and duration of delta-, theta- and slow-alpha-rhythmic microstates were associated with unawareness, whereas the probability for the occurrence and duration of fast-alpha-rhythmic microstates were associated with consciousness. In conclusion, resting EEG has a potential value in revealing NCC. This work may have implications for clinical care and medical-legal decisions in patients with disorders of consciousness.

The aim of this study was to evaluate the presence of neuromuscular involvement in patients in vegetative and minimally conscious states (VS, MCS) following acute brain injury. Twenty-two patients (11 in VS, 11 in MCS) admitted to a rehabilitation department underwent nerve conduction, electromyography (EMG) for spontaneous activity and direct muscle stimulation (DMS). Twenty (90.9%) showed abnormal nerve conduction studies, 19 (86.4%) had spontaneous EMG activity, and 7 (31.8%) had abnormal DMS. The time spent in the intensive care unit correlated significantly with the amplitude of the compound muscle action potential of the ulnar nerve and with the amplitude of the sensory nerve action potential of the sural nerve (p < 0.05). No significant differences were found between patients in VS and MCS. Neurophysiological data indicative of neuromuscular involvement are common in patients in VS and MCS. This study underlines the need to implement strategies to prevent and to treat neuromuscular complications in patients in VS and MCS.

To evaluate kinematic features in cervical dystonia (CD) patients by means of a motion analysis system (Fastrack-Polhemus, Colchester VT, USA). Small study sample. Ambulatory care. 15 CD patients and 10 healthy subjects. Not applicable. Posture at rest and voluntary movements in both groups. Posture at rest in CD patients was impaired in all planes; only 20% of the patients exhibited complex dystonic patterns at clinical evaluation, whereas more than 90% of them had complex ones at kinematic evaluation. The analysis of voluntary motion revealed a reduced range of voluntary excursion and increased execution time; the impairment was higher when the patients moved their heads towards the anti-dystonic side. Fastrack system is a sensitive tool in kinematic evaluation of CD, as it provides useful quantitative information on rest position and on motion in CD patients and may consequently improve the management of this disease.

Objective: To test whether abnormal sensorimotor plasticity in focal hand dystonia is a primary abnormality or is merely a consequence of the dystonic posture. Methods: This study used the paired associative stimulation (PAS) paradigm, an experimental intervention, capable of producing long term potentiation (LTP) like changes in the sensorimotor system in humans. PAS involves transcranial magnetic stimulation combined with median nerve stimulation. 10 patients with cranial and cervical dystonia, who showed no dystonic symptoms in the hand, and nine patients with hemifacial spasm (HFS), a non-dystonic condition, were compared with 10 healthy age matched controls. Motor evoked potential amplitudes and cortical silent period (CSP) duration were measured at baseline before PAS and for up to 60 min (T0, T30 and T60) after PAS in the abductor pollicis brevis and the first dorsal interosseus muscles. Results: Patients with dystonia showed a stronger increase in corticospinal excitability than healthy controls and patients with HFS. In addition, patients with dystonia showed a loss of topographical specificity of PAS induced effects, with a facilitation in both the median and ulnar innervated muscles. While PAS conditioning led to a prolonged CSP in healthy controls and patients with HFS, it had no effect on the duration of the CSP in patients with cranial and cervical dystonia. Conclusion: The data suggests that excessive motor cortex plasticity is not restricted to the circuits clinically affected by dystonia but generalises across the entire sensorimotor system, possibly representing an endophenotypic trait of the disease.

Seizures affect about a quarter of patients with disorders of consciousness (DOC) after a coma.We investigated whether the presence of epileptiform abnormalities (EAs) in the electroencephalogram (EEG) of patients with DOC may predict the occurrence of seizures. Moreover, we evaluated whether EAs have a prognostic role in these patients.This was a retrospective single-center cohort study of patients hospitalized between January 2005 and December 2014 in a rehabilitation department (mean time from acute brain injury: 46.1 days). We analyzed 30-minute EEGs at admittance for 112 patients with unresponsive wakefulness syndrome (UWS) or in a minimally conscious state (MCS), then compared occurrence of seizures over the following three months across patients with absent, unilateral, and bilateral EAs (generalized or bilateral independent). Outcomes at three months were assessed in the same groups using the Coma Recovery Scale Revised.Epileptiform abnormalities were observed in 38 patients (33.9%). Of these, 25 were unilateral, and 13 were bilateral. Seizures occurred in 84.6% of patients with bilateral EAs, which was significantly higher than in patients without EAs (10.8%, p0.001) or with unilateral EAs (24%, p=0.001). The presence of EAs was not related to etiology or different DOC and did not significantly affect outcomes at three months.Patients with EAs at admission to a rehabilitation department have an increased risk of seizures. Specifically, most patients with bilateral EAs had seizures within the following 3 months. Evaluation of EAs in EEGs of patients with DOC may give valuable information in the management of antiepileptic drug treatment.

Botulinum toxin injected into a muscle may diffuse to nearby muscles thus producing unwanted effects. In patients with hemifacial spasm, we evaluated clinically and neurophysiologically, whether botulinum toxin type A (BoNT-A) diffuses from the injection site (orbicularis oculi) to untreated muscles (orbicularis oris from the affected side and orbicularis oculi and oris from the unaffected side). We studied 38 patients with idiopathic hemifacial spasm. Botulinum toxin was injected into the affected orbicularis oculi muscle alone (at 3 standardized sites) at a clinically effective dose. Patients were studied before (T0) and 3-4 weeks after treatment (T1). We evaluated the clinical effects of botulinum toxin and muscle strength in the affected and unaffected muscles. We also assessed the peak-to-peak amplitude compound muscle action potential (CMAP) recorded from the orbicularis oculi and orbicularis oris muscles on both sides after supramaximal electrical stimulation of the facial nerve at the stylomastoid foramen. In all patients, botulinum toxin treatment reduced muscle spasms in the injected orbicularis oculi muscle and induced no muscle weakness in the other facial muscles. The CMAP amplitude significantly decreased in the injected orbicularis oculi muscle, but remained unchanged in the other facial muscles (orbicularis oris muscle on the affected side and contra-lateral unaffected muscles). In conclusion, in patients with hemifacial spasm, botulinum toxin, at a clinically effective dose, induces no clinical signs of diffusion and does not reduce the CMAP size in the nearby untreated orbicularis oris or contralateral facial muscles.

Benign essential blepharospasm (BEB) is a focal cranial dystonia affecting eye closure. Here, we tested the hypothesis that BEB is associated with abnormal plasticity of the neuronal circuits mediating reflex blinks. In patients with BEB and healthy age-matched controls, we used the conditioning protocol introduced by Mao and Evinger (2001) to induce long-term potentiation (LTP)-like plasticity in trigeminal wide dynamic range neurons of the blink reflex circuit. High-frequency trains of electrical stimuli were repeatedly given over the right supraorbital nerve (SO) and timed to coincide with the R2 response elicited by a preceding SO stimulus. High-frequency stimulation (HFS) resulted in a long-lasting and input-specific potentiation of the R2 response in both groups, yet the facilitation of the R2 response was markedly increased in patients relative to controls. Botulinum toxin (BTX) injections in both orbicularis oculi muscles normalized the previously enhanced LTP-like plasticity of the R2 response. The increased responsiveness to HFS provides first-time evidence that LTP-like plasticity is increased in the trigeminal reflex circuit of patients affected by BEB. The results also show that the enhanced modifiability is not fixed in BEB, because BTX injections can transiently restore normal LTP-like plasticity. We propose that an abnormal corneal input induced by excessive blinking exacerbates increased LTP-like plasticity in BEB. BTX treatment removes the latter and restores plasticity toward normal values. Our results support the concept that maladaptive reorganization contributes to the pathophysiology of focal dystonias.

A 22-year-old patient presented with attacks of paroxysmal dystonia characterised by involuntary and uncontrollable movements affecting lower and upper limbs with sustained turning or twisting of the trunk. These motor paroxysms were induced by voluntary movements and lasted between 10 and 15 s with a frequency of 1-5 attacks per day. Transcranial magnetic stimulation of the motor cortex was found to induce motor paroxysms very similar to the spontaneous attacks. To evaluate motor cortex and brainstem excitability immediately after and between the attacks, a neurophysiological study was performed.

The value of spontaneous electroencephalography (EEG) oscillations in distinguishing patients in vegetative state (VS) and minimally conscious states (MCS) was studied.We quantified dynamic repertoire of EEG oscillations in resting condition with closed eyes in patients in VS and MCS. The exact composition of EEG oscillations was assessed by the probability-classification analysis of short-term EEG spectral patterns.The probability of delta, theta, and slow-alpha oscillations occurrence was smaller for patients in MCS than for VS. Additionally, only patients in MCS demonstrated fast-alpha oscillation occurrence. Depending on the type and composition of EEG oscillations, the probability of their occurrence was either etiology dependent or independent. The probability of EEG oscillations occurrence differentiated brain injuries with different etiologies.Spontaneous EEG oscillations have a potential value in distinguishing patients in VS and MCS.This work may have implications for clinical care, rehabilitative programs, and medical-legal decisions in patients with impaired consciousness states following coma due to acute brain injuries.The probability of delta, theta, and slow-alpha oscillations occurrence was smaller and the probability of fast-alpha oscillations occurrence was higher for patients in MCS than for patients in VS. The probability of EEG oscillations occurrence differentiated brain injuries with different etiologies. Spontaneous EEG has a potential value in distinguishing patients in VS and MCS.

Unresponsive wakefulness syndrome (UWS, previously known as vegetative state) occurs after patients survive a severe brain injury. Patients suffering from UWS have lost awareness of themselves and of the external environment and do not retain any trace of their subjective experience. Current data demonstrate that neuronal functions subtending consciousness are not completely reset in UWS; however, they are reduced below the threshold required to experience consciousness. The critical factor that determines whether patients will recover consciousness is the distance of their neuronal functions from this threshold level. Recovery of consciousness occurs through functional and/or structural changes in the brain, i.e., through neuronal plasticity. Although some of these changes may occur spontaneously, a growing body of evidence indicates that rehabilitative interventions can improve functional outcome by promoting adaptive functional and structural plasticity in the brain, especially if a comprehensive neurophysiological theory of consciousness is followed. In this review we will focus on the pathophysiological mechanisms involved in UWS and on the plastic changes operating on the recovery of consciousness.

Since most antiepileptic drugs (AEDs) have cognitive effects, the aim of this study was to evaluate the influence of AED therapy on the recovery of consciousness in 103 consecutive patients in a vegetative or minimally conscious state (VS, MCS). The levels of cognitive functioning (LCF) score was retrospectively compared after a three-month period of rehabilitation between patients who were medicated (n=54) and patients who were not medicated (n=49) with AEDs. Mean LCF scores in AED-medicated and nonmedicated patients were 2.2±0.7 and 2.3±0.8 at admission and 3.8±2.2 and 3.7±2.1 after three months, respectively (p values>0.05). These results did not change when we compared patients with the same etiology separately, with the same disorder of consciousness only, or patients treated with only one or more than one AED. In conclusion, AEDs did not affect the recovery of consciousness in a large cohort of patients in a VS or MCS following an acute brain injury.

Brain-derived neurotrophic factor (BDNF) is a neurotrophin that influences neuronal plasticity throughout life. Emergence from a vegetative state (VS) after a traumatic brain injury (TBI) implies that the brain undergoes plastic changes. A common polymorphism in the BDNF gene—BDNF Val66Met (referred to herein as BDNFMet)—impairs cognitive function in healthy subjects. The aim of this study was to determine whether the BDNFMet polymorphism plays a role in the recovery of consciousness and cognitive functions in patients in a VS after a TBI. Fifty-three patients in a VS 1 month after a TBI were included in the study and genotyped for the BDNFMet polymorphism. Scores of levels of cognitive functioning (LCF) at 1, 3, 6, and 12 months post-TBI were retrospectively compared in patients without (Val group), and with (Met group), the BDNFMet polymorphism. The BDNFMet polymorphism was detected in 20 out of the 53 patients. The mean LCF scores in the Val and Met groups were 1.6 – 0.5 and 1.4 – 0.5 at 1 month, 2.3 – 0.7 and 2.5 – 1.2 at 3 months, 3.3 – 1.7 and 3.5 – 1.7 at 6 months, and 4 – 1.9 and 3.9 – 1.8 at 12 months, respectively ( p > 0.05). The percentages of patients in the Val and Met groups who emerged from the VS were 36.4% and 30% at 3 months, 66.3% and 70% at 6 months, and 70% and 87.5% at 12 months ( p > 0.05), respectively. These findings provide evidence that the BDNFMet polymorphism is not involved in cognitive improvement in patients with a VS following TBI. Future studies should focus on the role of other BDNF polymorphisms in the recovery from a VS.

The occurrence of epileptic seizures was retrospectively evaluated in 96 patients in a vegetative or minimally conscious state during a three month period of hospitalization. Structural epilepsy was detected in 23 patients (24%) and its occurrence was three times greater in patients in a vegetative state than in those in a minimally conscious state. The occurrence of structural epilepsy did not affect the recovery of consciousness.

Patients in coma who fail to wake develop a condition known as a vegetative state (VS). While we know that some cortical activities exist in patients in VS, it remains unclear whether interneuronal modulation can be abnormal in the cerebral cortex of these patients. The aim of the study was to evaluate the inhibitory and excitatory interneuronal circuits in patients in VS following a traumatic brain injury.Cortical excitability was studied in 5 VS patients and in 10 healthy subjects using paired pulses transcranial magnetic stimulation (TMS). Resting motor threshold and intracortical inhibition and facilitation at short intervals (2 and 10 ms, respectively) were evaluated. Two patients were studied again after their level of consciousness transitioned into a minimally conscious state (MCS).Both intracortical inhibition and facilitation were significantly reduced in patients compared to healthy subjects (p0.05). In addition, these results did not significantly change in the 2 patients who evolved into a MCS.This is the first report showing an abnormal cortical excitability in patients in VS.Our findings suggest a pathophysiological base for future work aiming to restore the lack of interneuronal transmission in patients in VS.

Although standard EEG is performed routinely in patients with disorders of consciousness after coma, its prognostic value is still debated. The aim of the present study was to evaluate the role of standard EEG in predicting the recovery of cognitive functioning in patients affected by severe disturbances of consciousness after coma caused by cerebral anoxia. A standard EEG was recorded at admission to our Rehabilitation Department in 15 patients experiencing impaired consciousness because of cerebral anoxia. We quantified EEG abnormalities using the Synek scale (1988). Cognitive functioning was measured with the levels of cognitive functioning scale at the time of admission and after 3 months of recovery. EEG scores were significantly correlated with both levels of cognitive functioning scores at admission (P = 0.004) and change in levels of cognitive functioning score after 3 months (P < 0.001). The first correlation confirms the relationship between EEG and cognitive functioning, while the second correlation indicates the prognostic value of EEG in cognitive outcome. In conclusion, standard EEG is a simple and readily available tool with significant prognostic value in patients with disorders of consciousness after coma caused by cerebral anoxia.

Although several studies propose that the integrity of neuronal assemblies may underlie a phenomenon referred to as awareness, none of the known studies have explicitly investigated dynamics and functional interactions among neuronal assemblies as a function of consciousness expression. In order to address this question, EEG operational architectonics analysis (Fingelkurts and Fingelkurts 2001, 2008) was conducted in patients in minimally conscious (MCS) and vegetative states (VS) to study the dynamics of neuronal assemblies and operational synchrony among them as a function of consciousness expression. We found that in minimally conscious patients and especially in vegetative patients neuronal assemblies got smaller, their life span shortened and they became highly unstable. Furthermore, we demonstrated that the extent/volume and strength of operational synchrony among neuronal assemblies was smallest or even absent in VS patients, intermediate in MCS patients, and highest in healthy fully conscious subjects. All findings were similarly observed in EEG alpha as well as beta1 and beta2 frequency oscillations. The presented results support the basic tenets of operational architectonics theory of brain–mind functioning and suggest that EEG operational architectonics analysis may provide an objective and accurate means of assessing signs of (un)consciousness in patients with severe brain injuries. Therefore, this methodological approach may complement the existing “gold standard” of behavioral assessment of this population of challenging patients and inform the diagnostic and treatment decision-making processes.

Castiglione A, Bagnato S, Boccagni C, Romano MC, Galardi G. Efficacy of intra-articular injection of botulinum toxin type A in refractory hemiplegic shoulder pain. Objective To evaluate the efficacy of intra-articular injection of botulinum toxin type A (BTX-A) in relieving hemiplegic shoulder pain (HSP). Design Pilot study with assessments before and after BTX-A intra-articular injection. Setting Hospital rehabilitation department. Participants Patients (N=5) with HSP refractory to standard treatments and pain score at rest greater than 7 on a pain visual analog scale (VAS) of 0 to 10cm. Intervention Intra-articular BTX-A injection. Main Outcome Measure Variation in VAS score at rest and during 90° passive arm abduction 2 and 8 weeks after BTX-A intra-articular injection. Results Baseline VAS score was 8.7±1 at rest and 9.8±0.4 during passive arm abduction. It clearly decreased at 2 (1.5±1.1 at rest, P =.001; 3±1.2 during arm abduction, P P =.001; 2.3±1.1 during arm abduction, P Conclusions We found a strong correlation between intra-articular BTX-A injection and pain relief in patients with HSP. This result could provide the rationale for blind randomized controlled trials designed to better evaluate the safety and efficacy of intra-articular BTX-A injection in patients with refractory HSP.

During the last decades, many robotic platforms aimed at post-stroke neurorehabilitation of locomotion have been developed. These devices have been designed to enhance the possibilities of conventional rehabilitation providing safe, highly accurate, intensive and prolonged treatments. Nevertheless, up to now, robotic aided therapy has not yet promoted improvements of the motor performance significantly greater than those achieved by the conventional therapy. According to previous studies, we believe that this result may be partially ascribed to two main issues: the rehabilitation mediated by robots is usually provided too late from the trauma and it mainly consists of passive and cyclic manipulation of the legs. Our proposal to overcome some of the supposed limits is NEUROBike, an operative mechatronic platform able to lead leg manipulation as soon as possible after the trauma, that is when patients still lie on their own beds. Moreover, NEUROBike has been designed to provide both passive and cyclic manipulation of leg joints with trajectories similar to those related to natural walking, and motor task involving random efforts. This work presents the comparison between desired and measured leg joint trajectories while NEUROBike provides cyclic and passive leg manipulation. The results show that angular excursions at proximal joints were reasonably comparable with those obtained by the velocity based model even though they were affected by a positive offset involving emphasized flexion of hip and knee during the gait cycle.

The ability to recognise one's own face is crucial for self-identity formation and it plays a key role in the development of social interactions. Our starting hypothesis was that own-face recognition may be a psychophysiological phenomenon capable of activating the vegetative system in a peculiar manner, via sympathetic pathways. To test this hypothesis we studied the sympathetic skin responses (SSRs) evoked in 18 healthy subjects by the image of their own faces and by six other different visual stimuli. The SSRs were enhanced when participants were shown their own faces. Both SSR area and SSR amplitude contributed to this phenomenon. This work may offer new insights into the psycho- physiological processes involved in own-face recognition; moreover, the SSR could be a useful tool for future studies of patients affected by neuropsychiatric disorders presenting impairment of own-face recognition or representation of self-identity.

Objective To investigate the prognostic value of standard electroencephalogram (EEG) in predicting the improvement of the level of consciousness in patients suffering from severe disturbances of consciousness following coma caused by acute brain injuries. Methods A standard EEG was recorded at admission in our rehabilitation department in a total of 46 patients with impaired consciousness states following coma (22 patients with traumatic brain injuries, 24 patients with non-traumatic brain injuries). We quantified the EEG abnormalities using the scale of Synek (1988) and correlated them with the basal level of cognitive functioning (LCF) scale score and with its variation after three months. Results EEG scores correlated with LCF scores at admission ( p 0.01) and with LCF scores’ variation after three months ( p 0.01) in patients with traumatic brain injury; EEG scores correlated only with LCF scores variation after three months ( p Conclusions Standard EEG, analysed using the Synek scale, has a good prognostic value in both groups of patients with disorders of consciousness. Significance This work may have implications for clinical care, rehabilitative programs and medical–legal decisions in patients with impaired consciousness states following coma due to acute brain injuries.

In patients with hemispheric stroke, abnormal motor performances are described also in the ipsilateral limbs. They may be due to a cortical reorganization in the unaffected hemisphere; moreover, also peripheral mechanisms may play a role. To explore this hypothesis, we studied motor performances in 15 patients with hemispheric stroke and in 14 patients with total knee arthroplasty, which have a reduced motility in the prosthesized leg. Using the unaffected leg, they performed five superimposed circular trajectories in a prefixed pathway on a computerized footboard, while looking at a marker on the computer screen. The average trace error was significantly different between the groups of patients and healthy subjects [F ((2,25)) = 7.9; p = 0.003]; on the contrary, the test time execution did not vary significantly. In conclusion, both groups of patients showed abnormal motor performances of the unaffected leg; this result suggests a likely contribution of peripheral mechanisms.

Purpose Despite clinical evidences that hypothyroidism is often associated with cognitive dysfunction, affective disorders and psychosis, the effects of thyroid hormone deficiency on the adult brain have been largely unexplored. We investigated the hypothesis that hypothyroidism might affect cortical excitability and modulates inhibitory and excitatory cortical circuits by using Transcranial Magnetic Stimulation. Materials and methods Cortical excitability was probed in 10 patients with overt hypothyroidism and 10 age-matched healthy controls. We tested motor thresholds and corticospinal excitability, cortical silent period and peripheral silent period, short interval intracortical inhibition, intracortical facilitation. Patients were evaluated at the time of diagnosis, as well as after 3 and 6 months replacement therapy with l -thyroxin. Results At baseline, patients showed decreased cortical excitability, with increased resting and active motor threshold and decreased steepness of the motor evoked potential recruitment curves. These changes were paralleled by longer cortical silent period and decreased short interval intracortical inhibition. After 3 months replacement therapy, all the parameters but short interval intracortical inhibition were restored to normal values. Short interval intracortical inhibition returned to normal values only after 6 months of replacement therapy. Conclusions Thyroid hormones are needed to modulate cortical excitability and cortical inhibitory circuits in adults.

The aim of this study was to identify a neurophysiological marker of upper motoneuron involvement in patients with sporadic amyotrophic lateral sclerosis (ALS). For this purpose we evaluated the after-effects of trans- cranial direct-current stimulation (tDCS) on excitability of the motor cortex of eight ALS patients and eight healthy controls. Healthy controls showed a transient polarity-specific change in corticospinal excitability of about 45%, with anodal tDCS inducing facilitation and cathodal tDCS leading to inhibition, whereas no change could be induced in ALS patients after either type of tDCS. It is likely that the lack of tDCS after-effects in ALS is the result of alterations of the motoneuronal membrane or, alternatively, may represent an electrophysi- ological correlate of disordered glutamate neurotransmission. Further studies are warranted to confirm these results. The present findings may lead to a new, reliable electrophysiological marker of upper motoneuronal involvement in ALS. Muscle Nerve 35: 620-624, 2007

We investigated the hypothesis that Parkinsons's disease (PD) is associated with abnormal plasticity of the neuronal circuits mediating blink reflex. We induced long-term potentiation (LTP)-like plasticity in trigeminal wide dynamic range neurons of the blink reflex circuit by pairing an high-frequency train of electrical stimuli over the right supraorbital nerve (SO) coincident with the R2 response elicited by a preceding SO stimulus. The facilitation of the R2 response after the induction protocol was markedly decreased in patients relative to controls. Treatment with dopaminergic drugs normalized the LTP-like plasticity of the R2 response. We conclude that nigrostriatal denervation disrupts LTP-like plasticity in the trigeminal reflex circuit.

Repetitive transcranial magnetic stimulation (rTMS) or repetitive electrical peripheral nerve stimulation (rENS) can induce changes in the excitability of the human motor cortex (M1) that is often short-lasting and variable, and occurs only after prolonged periods of stimulation. In 10 healthy volunteers, we used a new repetitive paired associative stimulation (rPAS) protocol to facilitate and prolong the effects of rENS and rTMS on cortical excitability. Sub-motor threshold 5 Hz rENS of the right median nerve was synchronized with submotor threshold 5 Hz rTMS of the left M1 at a constant interval for 2 min. The interstimulus interval (ISI) between the peripheral stimulus and the transcranial stimulation was set at 10 ms (5 Hz rPAS10ms) or 25 ms (5 Hz rPAS25ms). TMS was given over the hot spot of the right abductor pollicis brevis (APB) muscle. Before and after rPAS, we measured the amplitude of the unconditioned motor evoked potential (MEP), intracortical inhibition (ICI) and facilitation (ICF), short- and long-latency afferent inhibition (SAI and LAI) in the conditioned M1. The 5 Hz rPAS25ms protocol but not the 5 Hz rPAS10ms protocol caused a somatotopically specific increase in mean MEP amplitudes in the relaxed APB muscle. The 5 Hz rPAS25ms protocol also led to a loss of SAI, but there was no correlation between individual changes in SAI and corticospinal excitability. These after-effects were still present 6 h after 5 Hz rPAS25ms. There was no consistent effect on ICI, ICF and LAI. The 5 Hz rENS and 5 Hz rTMS protocols failed to induce any change in corticospinal excitability when given alone. These findings show that 2 min of 5 Hz rPAS25ms produce a long-lasting and somatotopically specific increase in corticospinal excitability, presumably by sensorimotor disinhibition.

Objective To assess motor cortex excitability, motor preparation and imagery in patients with unilateral cerebellar stroke with damage of the dentate nucleus by using transcranial magnetic stimulation (TMS). Method Eight patients with unilateral cerebellar lesions due to tromboembolic stroke and 10 age matched healthy subjects were enrolled. Resting (RMT) and active (AMT) motor threshold, cortical and peripheral silent period, evaluation of motor imagery, reaction time and premovement facilitation of motor evoked potential (MEP) were tested bilaterally using TMS. Results The RMT and AMT were found to be increased contra lateral to the affected cerebellar hemisphere while the cortical silent period was prolonged. In addition the amount of MEP facilitation during motor imagery and the pre-movement facilitation were reduced in the motor cortex contra lateral to the affected cerebellar hemisphere. The reaction time, performed with the symptomatic hand, was slower. Conclusions On the whole, our data confirm a role for the cerebellum in maintaining the excitability of primary motor area. Furthermore, patients with unilateral cerebellar stroke exhibit lateralized deficit of motor preparation and motor imagery. Significance Our results add to evidence that cerebellum contributes to specific aspects of motor preparation and motor imagery.

Objective TMS techniques have provided controversial information on motor cortical function in Huntington's disease (HD). We investigated the excitability of motor cortex in patients with HD using repetitive transcranial magnetic stimulation (rTMS). Methods Eleven patients with HD, and 11 age-matched healthy subjects participated in the study. The clinical features of patients with HD were evaluated with the United Huntington's Disease Rating Scale (UHDRS). rTMS was delivered with a Magstim Repetitive Magnetic Stimulator through a figure-of-8 coil placed over the motor area of the first dorsal interosseus (FDI) muscle. Trains of 10 stimuli were delivered at 5 Hz frequency and suprathreshold intensity (120% resting motor threshold) with the subjects at rest and during voluntary contraction of the target muscle. Results In healthy subjects at rest, rTMS produced motor evoked potentials (MEPs) that increased in amplitude over the course of the trains. Conversely in patients, rTMS left the MEP size almost unchanged. In both groups, during voluntary contraction rTMS increased the silent period (SP) duration. Conclusions Because rTMS modulates motor cortical excitability by activating cortical excitatory and inhibitory interneurons these findings suggest that in patients with HD the excitability of facilitatory intracortical interneurones is decreased. Significance We suggest that depressed excitability of the motor cortex in patients with HD reflects a disease-related weakening of cortical facilitatory mechanisms.

We used the paired associative stimulation (PAS) technique to investigate associative plasticity of the sensorimotor cortex in 16 Parkinson's disease (PD) patients off and on therapy and in 10 age-matched controls. After PAS, motor evoked potential (MEP) amplitudes increased more and the cortical silent period showed a reduced prolongation in patients off therapy than in controls. These changes lasted for at least 30 minutes. In addition, MEP amplitudes increased in a less focal manner in patients off therapy than in controls. After patients received dopaminergic therapy, these abnormalities normalized. The abnormal responsiveness of sensorimotor cortex neurons to PAS in PD patients off therapy probably reflects disordered plasticity within the motor cortex.