Development and Rasch Validation of an Observational Assessment Tool of Upper Limb Functional Impairment in Stroke Survivors: Functional Assessment Test for Upper Limb.

OBJECTIVE: To develop and validate a quick observational clinical tool, the Functional ASsessment Test for Upper Limb (FAST-UL), for the evaluation of upper limb impairment in goal-directed functional-oriented motor tasks after stroke. DESIGN: Observational, cross-sectional, psychometric study. SETTING: Inpatient and outpatient rehabilitation clinic. PARTICIPANTS: A total of 188 post-stroke survivors (mean age 65.2±17.7 years, 61% men, 48% with ischemic stroke and 66% in the sub-acute phase; N=188). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Principal component analysis and Rasch analysis through a Partial Credit Model were used to assess the structure and psychometric properties of the 5 items of the FAST-UL (Hand to Mouth [HtM], Reach to Target, Prono-Supination, Grasp and Release, and Pinch and Release [PaR]). RESULTS: The Cronbach's α equal to 0.96 was indicative of an acceptable internal consistency; the reliability, as measured through the Person Separation Reliability equal to 0.87, was good. The FAST-UL tool was unidimensional. All the FAST-UL items were found to fit well the Rasch measurement model. The easiest to perform FAST-UL item was the HtM movement while the most difficult was the PaR movement. CONCLUSIONS: The FAST-UL is a quick, easy-to-administer observational assessment tool of upper limb motor impairment in post-stroke survivors with good item-level psychometric properties.

Cotinine levels influence the risk of rupture of brain aneurysms.

Cotinine, the primary metabolite of nicotine, is currently regarded as the best biomarker of tobacco smoke exposure. We aim to assess whether cotinine levels are associated with (1) intracranial aneurysm and (2) intracranial aneurysm rupture. METHODS: We performed a single-center case-control study. Cases were consecutive patients admitted with diagnosis of brain aneurysm (ruptured or unruptured). We randomly selected controls without intracranial aneurysm from the same source population that produced the cases. Smoking data were collected by questionnaire, and serum levels of cotinine were used as an objective measure of nicotine exposure. Logistic regression models were used to assess the relationship between cotinine levels and aneurysm rupture. RESULTS: We included 86 patients with intracranial aneurysm and 96 controls. Smoking status (p < .001), cotinine levels (p = .009), and female sex (p = .006) were associated with diagnosis of intracranial aneurysm. In the multivariate analysis, controlling for sex, smoker status and age, levels of cotinine were independently associated with aneurysm rupture (OR 1.53, 95% CI 1.10-2.13, p = .012). CONCLUSIONS: Our results suggest that high cotinine levels in smokers with brain aneurysm are significantly associated with high rupture risk, independently of smoker status, age, and sex.

The Effect of Verbal Encouragement on Performance and Muscle Fatigue in Swimming.

Background and Objectives: Verbal encouragement (VE) can be used to enhance performance in several sports, even though no studies have been conducted among swimmers and only a few effects have been reported in elite athletes. Besides influencing motor performance, VE is also known to enhance the physical load, thus potentially increasing the probability of developing fatigue. With this in mind, this study aimed to explore the effects of VE in swimmers in order to fill in the knowledge gap concerning the aquatic environment. Materials and Methods: Each athlete swam a maximal 200 m freestyle trial under two different conditions: one trial with VE and the other without VE. The two main outcome measures were: (1) performance velocity (m/s); and (2) muscle fatigue, investigated by means of surface electromyography. Sixty swimmers were recruited, aged 18.63 ± 3.46 years (median 18 years), 28 men (47%), and 32 women (53%), with 7.03 ± 3.9 years of experience. Results: With VE, performance significantly improved in the swim trial (p < 0.001, effect size (ES) −0.95, large). When breaking the results down into the first half (first (0−100 m) vs. the second half (100−200 m)), the ES was large in the first part (−1.11), indicating an improvement in performance. This worsened, however, in the second part of the trial (ES 0.63). In the multivariate analysis, years of experience were found to be a significant predictor of the change in overall performance (p = 0.011). There was a significant increase in muscle fatigue induced by VE, overall, and during the second half, but not during the first half of the trial. Conclusions: The present study indicates that VE during a middle-distance event (200 m) increases performance most in swimmers with little experience. However, it has a negative impact on fatigue.

Habituation of Somatosensory Evoked Potentials in Patients with Alzheimer's Disease and Those with Vascular Dementia.

Background and Objectives: The most prevalent dementia are Alzheimer's disease and vascular dementia. There is evidence that cortical synaptic function may differ in these two conditions. Habituation of cortical responses to repeated stimuli is a well-preserved phenomenon in a normal brain cortex, related to an underlying mechanism of synaptic efficacy regulation. Lack of habituation represents a marker of synaptic dysfunction. The purpose of this study was to assess the habituation of somatosensory evoked potentials (SEPs) in 29 patients affected by mild-to-moderate Alzheimer's disease (AD-type) or vascular (VD-type) dementia. Materials and Methods: All patients underwent a clinical history interview, neuropsychological evaluation, and neuroimaging examination. SEPs were elicited by electrical stimulation of the right median nerve at the wrist. Six-hundred stimuli were delivered, and cortical responses divided in three blocks of 200. Habituation was calculated by measuring changes of N20 amplitude from block 1 to block 3. SEP variables recorded in patients were compared with those recorded in 15 age- and gender-matched healthy volunteers. Results: SEP recordings showed similar N20 amplitudes in AD-type and VD-type patients in block 1, that were higher than those recorded in controls. N20 amplitude decreased from block 1 to block 3 (habituation) in normal subjects and in VD-type patients, whereas in AD-type patients it remained unchanged (lack of habituation). Conclusions: The findings suggest that neurophysiologic mechanisms of synaptic efficacy that underneath habituation are impaired in patients with AD-type dementia but not in patients with VD-type dementia. SEPs habituation may contribute to early distinction of Alzheimer's disease vs. vascular dementia.

Effects of Cerebellar tDCS on Inhibitory Control: Evidence from a Go/NoGo Task.

Response inhibition as an executive function refers to the ability to suppress inappropriate but prepotent responses. Several brain regions have been implicated in the process underlying inhibitory control, including the cerebellum. The aim of the present study was to explore the role of the cerebellum in executive functioning, particularly in response inhibition. For this purpose, we transitorily inhibited cerebellar activity by means of cathodal tDCS and studied the effects of this inhibition on ERP components elicited during a Go/NoGo task in healthy subjects. Sixteen healthy subjects underwent a Go/NoGo task prior to and after cathodal and sham cerebellar tDCS in separate sessions. A reduction in N2-NoGo amplitude and a prolongation in N2-NoGo latency emerged after cathodal tDCS whereas no differences were detected after sham stimulation. Moreover, commission errors in NoGo trials were significantly higher after cathodal tDCS than at the basal evaluation. No differences emerged between performances in Go trials and those after sham stimulation. These data indicate that cerebellar inhibition following cathodal stimulation alters the ability to allocate attentional resources to stimuli containing conflict information and the inhibitory control. The cerebellum may regulate the attentional mechanisms of stimulus orientation and inhibitory control both directly, by making predictions of errors or behaviors related to errors, and indirectly, by controlling the functioning of the cerebral cortical areas involved in the perception of conflict signals and of the basal ganglia involved in the inhibitory control of movement.

The Cerebellum Modulates Attention Network Functioning: Evidence from a Cerebellar Transcranial Direct Current Stimulation and Attention Network Test Study.

The functional domain of the cerebellum extends beyond its traditional role in motor control. In recent years, this structure has increasingly been considered to play a crucial role even in cognitive performance and attentional processes. Attention is defined as the ability to appropriately allocate processing resources to relevant stimuli. According to the Posnerian model, three interacting networks modulate attentive processes: the alerting, orienting, and executive networks. The aim of this study was to investigate the role played by the cerebellum in the functioning of the attentive networks using the Attention Network Test (ANT). We studied the effects of transcranial direct current stimulation (tDCS), delivered over the cerebellum in cathodal, anodal, and sham sessions, on ANT parameters in healthy subjects. After anodal and sham tDCS, the efficiency of the three attention networks remained stable, and a significant reduction in reaction time (RT) following the task repetition was observed for both congruent and incongruent targets, indicating a learning effect. After cathodal stimulation, instead, while the efficiency of the alerting and orienting networks remained stable, the efficiency of the executive network was significantly reduced. Moreover, a significant reduction in RT was observed for the congruent target alone, with no difference being detected for the incongruent target, indicating that cerebellar inhibition caused an attentive executive dysfunction specifically related to the ability to process complex stimuli in which conflict signals or errors are present. These results point to a role of the cerebellum, a subcortical structure that is thought to affect error processing both directly, by making predictions of errors or behaviors related to errors, and indirectly, by managing the functioning of brain cortical areas involved in the perception of conflicting signals, in the functioning of the attentional networks, particularly the executive network.

Attentional functioning in individuals with 22q11 deletion syndrome: insight from ERPs.

The 22q11 deletion syndrome (22q11DS), or DiGeorge syndrome (DG), is one of the most common genetic deletion syndromes. DG also carries a high risk for psychiatric disorders, with learning disabilities frequently being reported. Impairments in specific cognitive domains, such as executive functioning and attention, have also been described. The aim of this study was to investigate attentional functioning in a group of subjects with DG using ERPs, and in particular the P300 and CNV components. We studied ten patients with DG and ten healthy subjects that performed a P300 Novelty task and a CNV motor task. P3b amplitude was significantly lower in patients than in controls, while P3b latency was comparable in patients and controls. The P3a parameters were similar in both groups. All CNV amplitudes were significantly lower in DG patients than in controls. DG patients displayed slower reaction times in the CNV motor task than healthy subjects. These results point to a cognitive dysfunction related above all to executive attentional processing in DG patients. In particular, a specific difficulty emerged in selective attention and in the ability to orient and to sustain the anticipatory attention required for an executive motor response.

Diplopia as isolated presentation of varicella zoster central nervous system reactivation.

Here, we report a patient who developed diplopia secondary to a right cranial nerve III and IV palsy, as well as fever and headache. Cerebrospinal fluid analysis (CSF) showed high varicella-zoster virus (VZV)-DNA viral load (>300,000,000 copies/ml). VZV antibodies in CSF was ≥1:16. Diagnosis of neurological reactivation of VZV infection was made without the presence of characteristic vesicular rash. Quantitative real-time PCR for VZV and intrathecal dosage of VZV IgM and IgG should be performed in cases suspected for viral encephalitis and also in all patients with not otherwise attributable cranial nerve lesions.

Attention in Parkinson's disease with fatigue: evidence from the attention network test.

Fatigue is a non-specific symptom that is common in chronic diseases and represents one of the most disabling symptoms in Parkinson's disease. PD patients often experience cognitive deficits related above all to executive functions. The relationship between cognitive changes and fatigue in PD patients has not been explored in depth. The Attention Network Test (ANT) is a rapid, widely used test to measure the efficiency of three attentional networks, i.e., alerting, orienting, and executive, by evaluating reaction times (RTs) in response to visual stimuli. To assess the association between fatigue and the efficiency of the attentional networks, according to the Posnerian view, ANT was administered to 15 parkinsonian patients with fatigue (PFS-16 > 2.95), 17 parkinsonian patients without fatigue, and 37 age- and sex-matched healthy controls. Anxiety, depression, quality of sleep, and quality of life were also assessed. Parkinsonian patients displayed significantly longer RTs and lower executive network efficiency than controls. Patients with fatigue displayed significantly lower executive network efficiency than patients without fatigue. Moreover, patients with fatigue exhibited a lower accuracy than either patients without fatigue or controls. Finally, patients without fatigue displayed a more efficient alerting network than either patients with fatigue or controls. Although the pathogenesis of fatigue is multifactorial, our results indicate that fatigue may be closely related to an alteration of the striato-thalamo-cortical loop connecting the neostriatum to the prefrontal cortex, which is also responsible for the executive dysfunction that is typical of Parkinson's disease.

Electromyographic assessment of paratonia.

Many years after its initial description, paratonia remains a poorly understood concept. It is described as the inability to relax muscles during muscle tone assessment with the subject involuntary facilitating or opposing the examiner. Although related to cognitive impairment and frontal lobe function, the underlying mechanisms have not been clarified. Moreover, criteria to distinguish oppositional paratonia from parkinsonian rigidity or spasticity are not yet available. Paratonia is very frequently encountered in clinical practice and only semi-quantitative rating scales are available. The purpose of this study is to assess the feasibility of a quantitative measure of paratonia using surface electromyography. Paratonia was elicited by performing consecutive metronome-synchronized continuous and discontinuous elbow movements in a group of paratonic patients with cognitive impairment. Goniometric and electromyographic recordings were performed on biceps and triceps brachii muscles. Facilitatory (mitgehen) and oppositional (gegenhalten) paratonia could be recorded on both muscles. After normalization with voluntary maximal contraction, biceps showed higher paratonia than triceps. Facilitatory paratonia was higher than oppositional on the biceps. Movement repetition induced increased paratonic burst amplitude only when flexion and extension movements were performed continuously. Both facilitatory and oppositional paratonia increased with movement repetition. Only oppositional paratonia increased following faster movements. This is the first study providing a quantitative and objective characterization of paratonia using electromyography. Unlike parkinsonian rigidity, oppositional paratonia increases with velocity and with consecutive movement repetition. Like spasticity, oppositional paratonia is velocity-dependent, but different from spasticity, it increases during movement repetition instead of decreasing. A quantitative measure of paratonia could help better understanding its pathophysiology and could be used for research purposes on cognitive impairment.

Learning "How to Learn": Super Declarative Motor Learning Is Impaired in Parkinson's Disease.

Learning new information is crucial in daily activities and occurs continuously during a subject's lifetime. Retention of learned material is required for later recall and reuse, although learning capacity is limited and interference between consecutively learned information may occur. Learning processes are impaired in Parkinson's disease (PD); however, little is known about the processes related to retention and interference. The aim of this study is to investigate the retention and anterograde interference using a declarative sequence learning task in drug-naive patients in the disease's early stages. Eleven patients with PD and eleven age-matched controls learned a visuomotor sequence, SEQ1, during Day1; the following day, retention of SEQ1 was assessed and, immediately after, a new sequence of comparable complexity, SEQ2, was learned. The comparison of the learning rates of SEQ1 on Day1 and SEQ2 on Day2 assessed the anterograde interference of SEQ1 on SEQ2. We found that SEQ1 performance improved in both patients and controls on Day2. Surprisingly, controls learned SEQ2 better than SEQ1, suggesting the absence of anterograde interference and the occurrence of learning optimization, a process that we defined as "learning how to learn." Patients with PD lacked such improvement, suggesting defective performance optimization processes.

Insights from ERPs into attention during recovery after cerebellar stroke: a case report.

The role of the cerebellum in cognitive performance and attentional processes is a focus of research in recent years. We investigated the P300 component in a patient with a left posterior cerebellar ischemic stroke during both the acute phase and over 4 weeks of follow-up. After stroke, auditory event-related potentials showed a reduction in P3 amplitude, which appears to improve instead after 4 weeks of follow-up. These event-related potential findings could suggest a specific neural pattern of disruption in selective attention during the discrimination processes of the stimulus following a posterior cerebellar lesion. A recovery is observed in the long term.

The Role of the Right Dorsolateral Prefrontal Cortex in Phasic Alertness: Evidence from a Contingent Negative Variation and Repetitive Transcranial Magnetic Stimulation Study.

Phasic alertness represents the ability to increase response readiness to a target following an external warning stimulus. Specific networks in the frontal and parietal regions appear to be involved in the alert state. In this study, we examined the role of the right dorsolateral prefrontal cortex (DLPFC) during the attentional processing of a stimulus using a cued double-choice reaction time task. The evaluation of these processes was conducted by means of Event-Related Potentials (ERPs), in particular by using the Contingent Negative Variation (CNV), and repetitive 1-Hz Transcranial Magnetic Stimulation (rTMS). Transient virtual inhibition of the right DLPFC induced by real 1-Hz rTMS stimulation led to a significant decrease in total CNV and W1-CNV areas if compared with the basal and post-sham rTMS conditions. Reaction times (RTs) did not decrease after inhibitory rTMS, but they did improve after sham stimulation. These results suggest that the right DLPFC plays a crucial role in the genesis and maintenance of the alerting state and learning processes.

The effect of age on post-activation depression of the upper limb H-reflex.

PURPOSE: Post-activation depression (PaD) refers to the inhibition of the H-reflex induced by a preceding conditioning stimulus able to activate the afferents mediating the H-reflex itself. PaD can be investigated assessing the frequency-related depression of the H-reflex. This parameter, which is highly correlated to the severity of spasticity, has been used in the longitudinal assessment of spastic patients, in particular to assess the effect of drugs and rehabilitation over the years. However, in such longitudinal assessment, changes observed might be age related and not only disease related. The aim of this study was to investigate the possible age effects on PaD. METHODS: The frequency-related depression of the flexor carpi radialis (FCR) H-reflex was examined in two groups of young (20 subjects; 28 ± 3 years) and aged (18 subjects; 69 ± 6 years) healthy subjects. PaD was evaluated by comparing the H-reflex amplitudes obtained with a stimulation frequency of 0.1 Hz with those obtained using higher frequencies (0.33-0.5-1-2 Hz). RESULTS: The results showed that frequency-related depression of the FCR H-reflex is similar in young and elderly subjects at all frequencies, with the exception of 2 Hz. CONCLUSION: Our study shows that ageing does not affect the frequency-related depression of the FCR H-reflex at the frequencies of 1 Hz or lower, supporting the reliability of this method to assess PaD in the clinical practice, particularly for the longitudinal assessment of spasticity. A decrease of GABA-ergic presynaptic inhibition seems to be the more likely explanation for the age-related changes that we observed at the frequency of 2 Hz.

Frequency of brain ventricular enlargement among patients with diabetes mellitus.

AIMS: To determine the prevalence of dilated ventricles and concomitant high blood glucose measures. METHODS: We retrieved blood glucose measures from the emergency department database and selected a subgroup of individuals having both the radiological marker Evans' index (EI) values and blood glucose measures. RESULTS: Out of 1221 consecutive patients submitted to axial Computed Tomography scans, a blood glucose measure was detected in 841 individuals. 176 scans (21 %) showed an EI > 0.30. According to the blood glucose categorization, diabetic patients were 104 (12 %), 25 of them (24 %) were dilated (mean EI 0.33). The age difference between dilated and not-dilated ventricles is about ten years in not-diabetic participants, whereas it is five years in diabetic participants. The age difference between dilated and not-dilated ventricles is about 10 years in diabetic men, whereas it zero in diabetic women. CONCLUSIONS: Pathological ventricular enlargement is more frequent in men and in the elderly. In diabetic patients (especially women), the cerebral ventricles enlarge faster than in non-diabetic individuals. Age, sex, and diabetes may interact in determining how cerebral ventricle size changes over time, especially in diabetic women, making routine brain imaging advisable in these patients after the age of 70 years.

Influence of rTMS over the left primary motor cortex on initiation and performance of a simple movement executed with the contralateral arm in healthy volunteers.

Repetitive transcranial magnetic stimulation (rTMS) affects cortical excitability according to the frequency of stimulation. Few data are available on the influence of rTMS applied over the primary motor cortex (M1) on motor performances in healthy volunteers. The aim of this study was to determine, through kinematic analysis, whether rTMS over the left M1 changes initiation and performance of movement executed with the contralateral arm. Nine healthy males completed a set of motor tasks, consisting of a single-joint rapid movement between two objects performed under three different behavioral conditions (self-initiated; externally triggered known, during which the subject could see where the target was positioned in advance; externally triggered unknown, during which the subject could not see where the target was positioned until he reached it). The tasks were performed in a randomized order in three different sessions, with a seven-day interval between each session: (1) without stimulation (baseline); (2) immediately after 1-Hz rTMS; (3) immediately after 10-Hz rTMS. We measured reaction time, movement time, calculated as the sum of the time taken to reach the target from movement onset (T1) and that taken to reach the target to movement termination (T2), acceleration and deceleration time on the velocity profile, as well as the ratio between them, and maximum speed and maximum acceleration. Reaction time, movement time, and T2 significantly increased after 1-Hz rTMS and decreased after 10-Hz rTMS, while the other parameters remained unchanged. Our results suggest that rTMS may modify both initiation and performance of a voluntary movement.