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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) (

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.

(1) Background: Sustained axonal degeneration may play a critical role in prolonged disorder of consciousness (DOCs) pathophysiology. We evaluated levels of neurofilament light chain (NFL), an axonal injury marker, in patients with unresponsive wakefulness syndrome (UWS) and in the minimally conscious state (MCS) after traumatic brain injury (TBI) and hypoxic-ischemic brain injury (HIBI). (2) Methods: This prospective multicenter blinded study involved 70 patients with prolonged DOC and 70 sex-/age-matched healthy controls. Serum NFL levels were evaluated at 1–3 and 6 months post-injury and compared with those of controls. NFL levels were compared by DOC severity (UWS vs. MCS) and etiology (TBI vs. HIBI). (3) Results: Patients’ serum NFL levels were significantly higher than those of controls at 1–3 and 6 months post-injury (medians, 1729 and 426 vs. 90 pg/mL, both p &lt, 0.0001). NFL levels were higher in patients with UWS than in those in MCS at 1–3 months post-injury (p = 0.008) and in patients with HIBI than in those with TBI at 6 months post-injury (p = 0.037). (4) Conclusions: Patients with prolonged DOC present sustained axonal degeneration that is affected differently over time by brain injury severity and etiology.

The sinking skin flap syndrome (SSFS), or syndrome of the trephined, is a pathological condition arising from the presence of large bone defects of the skull. Originally described by Grant and Norcross in patients with a skin flap depression following craniectomy [1], SSFS has a multifaceted clinical presentation, including chronic fatigue, headache, dizziness, impaired vigilance, motor deficits, cognitive deficits, epileptic seizures, and visual symptoms [2]. SSFS pathophysiology is related to the atmospheric pressure exerted on the brain through the craniectomy, inducing brain compression, changes in the cerebrospinal fluid (CSF) dynamics, impaired venous return, and decrease in the regional blood flow, alone or in combination [2]. In this report we describe a case of SSFS complicated by paradoxical uncal herniation due to diuretic therapy.

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.

Highlights • Muscle weakness after COVID-19 can be caused by critical illness myopathy. • Critical illness myopathy should be suspected in patients with long ICU stay. • Health systems must plan access to rehabilitative facilities after COVID-19., We describe a patient who developed diffuse and symmetrical muscle weakness after a long stay in the intensive care unit (ICU) due to coronavirus disease 2019 (COVID-19). The patient underwent a neurophysiological protocol, including nerve conduction studies, concentric needle electromyography (EMG) of the proximal and distal muscles, and direct muscle stimulation (DMS). Nerve conduction studies showed normal sensory conduction and low-amplitude compound muscle action potentials (CMAPs). EMG revealed signs of myopathy, which were more pronounced in the lower limbs. The post-DMS CMAP was absent in the quadriceps and of reduced amplitude in the tibialis anterior muscle. Based on these clinical and neurophysiological findings, a diagnosis of critical illness myopathy was made according to the current diagnostic criteria. Given the large number of patients with COVID-19 who require long ICU stays, many of these patients are very likely to develop ICU-acquired weakness, as did the patient described here. Health systems must plan to provide adequate access to rehabilitative facilities for both pulmonary and motor rehabilitative treatment after COVID-19.

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.

Acquired neuralgic amyotrophy, described for the first time by Parsonage and Turner, is a rare idiopathic disease that may occur in otherwise normal healthy individuals. It typically begins with sudden, unilateral shoulder pain that may also involve the neck and/or arm. Less frequently, the disease involves nerves other than those of the brachial plexus, such as phrenic nerves, resulting in dyspnoea. The diagnosis is based on the clinical presentation and is generally supported by electroneurography/electromyography. We report the case of a 45-year-old white man who was referred to our clinic for acute dyspnoea preceded by severe neck and right shoulder pain. Corticosteroid therapy ameliorated the clinical picture, but without a complete recovery. Keywords: Dyspnoea, Parsonage-turner syndrome, Neuralgic amyotrophy

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.

Diagnostic accuracy and reliable assessment of prognosis are challenging in patients in vegetative state (VS) and in minimally conscious state (MCS). This longitudinal multi-centric study aims to identify neurophysiological patterns with diagnostic and prognostic value. 59 patients in VS and 63 in MCS underwent clinical assessment by Coma Recovery Scale-Revised3 and neurophysiological evaluations of EEG background activity and reactivity, somatosensory evoked potential (SEP) and event related potential (ERP) at 63 months after brain-injury. Clinical outcome was evaluated at 6 months post-injury. EEG background activity and reactivity significantly differed between VS and MCS patients (p < .001), whereas the presence of cortical component N20 on SEP and P300 on ERP did not differ between the two groups. Good outcome was significantly more frequent in patients with moderately abnormal to normal EEG background activity than in patients with poor EEG background organization (p = .001), in patients showing EEG reactivity (p < .001) and in patients showing P300 (p = .016). The presence of SEP did not differ significantly between the two prognostic groups. Multimodal clinical and neurophysiological assessment could provide useful diagnostic and prognostic information for disorder of consciousness. This multicentric project calls for international standardization of diagnostic and prognostic procedures

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.

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.

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.

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.

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.

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 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.

Background. Patients with cardioembolic stroke due to atrial fibrillation (CE/AF stroke) seem to have a poorer functional recovery than those with non cardioembolic stroke. This may be ascribed to the heterogeneity between the samples of patients with and without CE/AF stroke. Aim. To compare the short-term outcome of patients with CE/AF stroke and with non-CE/AF stroke of same gender and similar age and level of disability and comorbidity. Methods. The functional independence measure (FIM) of 40 consecutive patients with CE/AF stroke was retrospectively evaluated at admission and discharge in our rehabilitation department. Each “case” was matched with a patient (“control”) of the same sex and similar age and FIM score at admission, affected by non-CE/AF stroke admitted to our department in the same period. Results. FIM score at admission and discharge was respectively and in patients with CE/AF stroke and and in patients with non-CE/AF stroke; no significant difference was found between the groups. Multivariate analysis showed an effect of the rehabilitation treatment and age on FIM score, whereas no effect was attributable to AF. Conclusions. The short-term outcome is similar in patients with and without CE/AF stroke.

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.

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.

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.

Robotic aided therapy has been developed in the last decades in order to improve the effects of gait rehabilitation on stroke patients. Although several platforms have nowadays used in clinical practice, contrasting results have been achieved with reduced significant improvements in stroke patients when they experience robotic based therapy. In particular, an improvement of the clinical outcome may be achieved by starting the rehabilitation process almost immediately after the stroke. To address this issue a new robotic system, called “NEUROBike”, has been developed. This approach is based on the hypothesis that a better recovery of the neuro-motor control of the leg could result from an early, intensive and task-oriented rehabilitation therapy. Therefore, the leg manipulation during the acute phase, following joint trajectories comparable with the ones obtained during natural walking, could improve the outcome of the rehabilitation. In this regard, desired trajectories of the end-effector of NEUROBike have been estimated in accordance with data collected from young and elderly people when walking on treadmill in a range of speeds from 0.5 to 1.3 m/s. Moreover, tracking performance of a traditional position control algorithm has been investigated. This paper is aimed at showing the first results obtained during the test of the platform. In the next months NEUROBike will be applied for the first clinical pilot studies.

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

Publisher Summary This chapter reviews the recent findings in cranial and cervical dystonia and discusses their contribution to the understanding of the pathophysiology of dystonia. Growing neurophysiological evidence suggests that in cranial and cervical dystonia, as well as in other forms of dystonia, sensorimotor integration is deranged. The sites of major impairment include the spinal cord, the brainstem, the basal ganglia, and the motor cortex. Dystonia is characterized by multilevel dysfunctions: some are intrinsic abnormalities, whereas others arise from maladaptive plasticity. Delayed movement initiation but normal peak velocity have been found for saccadic movements in patients with cranial dystonia, although no physiological study has investigated the speed of movement for eye opening and closing (periocular muscles), or for neck rotation, flexion or extension in patients with cranial or cervical dystonia. Some of these patients, nevertheless, perform voluntary movements of the upper limb slowly and with variable movement amplitude. At the spinal cord level, patients with cervical dystonia have an abnormal late (presynaptic) phase of reciprocal inhibition between forearm agonist and antagonist muscles. In the brainstem, although the organization of the intrinsic neural pathways is preserved, the excitability of the interneurones mediating the various reflex responses is enhanced. Cranial and cervical dystonia also leads to changes in the cortical inhibitory pathways other than those subserving intracortical inhibition. The transcranial magnetic stimulation (TMS)–evoked cortical silent period is shorter in involved and uninvolved cranial muscles in cranial dystonia and is even shorter when dystonia affects both upper and lower facial muscles.

Objective To investigate whether patients with end-stage renal disease (ESRD) in different stages of the disease and undergoing different treatments display alterations in cortical excitability. Method A total of 36 patients with ESRD were evaluated at different stages of the disease and under different treatment by using standard transcranial magnetic stimulation (TMS) parameters. Moreover patients under haemodialysis underwent a double-blind crossover study (mannitol vs placebo) in order to better elucidate the pathophysiology of the acute effects of haemodialysis on cortical excitability. Results Patients with ESRD in conservative therapy showed a significant reduction of short-interval intra-cortical inhibition (SICI). This alteration could be reversed by haemodialysis, peritoneal dialysis and by renal transplantation. After haemodialysis there was a significant increase of intra-cortical facilitation (ICF) inversely correlated with the drop in plasma osmolarity induced by the dialytic procedure. Mannitol infusion prevented the drop in plasma osmolarity and the haemodialysis-related changes in ICF. Conclusions ESRD patients showed alterations in cortical excitability that can be reversed by replacement therapies. We propose that the drop in plasma osmolarity is a key to the mechanism underlying post-haemodialysis cortical hyperexcitability. Significance The results of this study give further insight to the pathophysiology of brain abnormalities in patients with chronic renal failure.

We describe a patient who has been complaining of brief jerk-like, rhythmic, involuntary movements involving the second digit of the left hand for the last three months. These involuntary jerks produced an adduction movement of the second digit and were unaffected by peripheral sensory stimuli. In addition, the patient experienced loss of dexterity in the left hand. On examination the patient showed hypotrophy of the first dorsal interosseous (FDI) muscle of the left hand and a dissociated sensory loss involving the C8-T1 dermatomes. Magnetic resonance imaging of the brain and spinal cord revealed a tonsilar hemiation characteristic of the Chiari I malformation associated with a syrinx extending from C4 to D5 that did not communicate with the fourth ventricle. The electrophysiological evaluation indicated the presence of a focal myoclonus of spinal origin that is likely to be caused by the syrinx.

Transcranial magnetic stimulation (TMS) was employed before and after a single dose of gabapentin to evaluate how this drug affects the activity of excitatory and inhibitory circuits within the motor cortex. Eleven healthy volunteers were studied. For the evaluation of cortical excitability, the following parameters were taken into account: resting and active motor threshold (RMT, AMT); cortical silent period (CSP); and intracortical inhibition (ICI) and facilitation (ICF). Peripheral silent period (PSP) was also detected. All parameters were measured before and 3 and 24 hours after 800 mg gabapentin was administered in a single oral dose. Gabapentin deepened the ICI and suppressed the ICF at 3 h but not at 5 h after dosing. We conclude that, in the normal human brain, gabapentin may act on intracortical excitability by shifting the balance towards less excitation and more inhibition.

We describe a patient with insulin-dependent diabetes mellitus who noticed pain and stiffness in the neck and painful spasms and rigidity of the right thigh. Continuous motor unit activity was recorded in the lower limb muscles on the right side and in the cervical paraspinal muscles. Cutaneomuscular reflexes were at an abnormally low threshold recording from the muscles of the right leg. Laboratory investigation revealed anti-GAD antibodies in serum and oligoclonal bands in the cerebrospinal fluid. We conclude that the patient has atypical stiff-person syndrome.