Next-generation sequencing in Charcot-Marie-Tooth: a proposal for improvement of ACMG guidelines for variant evaluation.

BACKGROUND: The application of massive parallel sequencing technologies in the molecular analysis of Charcot-Marie-Tooth (CMT) has enabled the rapid and cost-effective identification of numerous potentially significant variants for diagnostic purposes. The objective is to reduce the number of variants, focusing only on those with pathogenic significance. The 2015 American College of Medical Genetics and Genomics (ACMG) guidelines aid in achieving this goal, but it is now evident that a pathology or gene-specific review of these rules is essential to avoid misinterpretations that may result from blindly applying the criteria. This study demonstrates how revised ACMG criteria, combined with CMT-specific literature data and expertise, can alter the final classification of a variant. METHODS: We reviewed ACMG criteria based on current knowledge of CMT and provided suggestions for adapting them to the specificities of CMT. RESULTS: Of the 226 index patients analysed, a diagnostic yield of 20% was obtained. It is worth noting that the 9% of cases had their final diagnosis changed with the application of the revised criteria, often resulting in the loss of the pathogenic classification of a variant. CONCLUSIONS: The widespread availability of high-throughput sequencing technologies has enabled genetic testing even for laboratories without specific disease expertise. Disease-specific ACMG criteria can be a valuable tool to prevent the proliferation of variants of uncertain significance and the misinterpretation of variants.

Thalamocortical bistable switch as a theoretical model of fibromyalgia pathogenesis inferred from a literature survey.

Fibromyalgia (FM) is an unsolved central pain processing disturbance. We aim to provide a unifying model for FM pathogenesis based on a loop network involving thalamocortical regions, i.e., the ventroposterior lateral thalamus (VPL), the somatosensory cortex (SC), and the thalamic reticular nucleus (TRN). The dynamics of the loop have been described by three differential equations having neuron mean firing rates as variables and containing Hill functions to model mutual interactions among the loop elements. A computational analysis conducted with MATLAB has shown a transition from monostability to bistability of the loop behavior for a weakening of GABAergic transmission between TRN and VPL. This involves the appearance of a high-firing-rate steady state, which becomes dominant and is assumed to represent pathogenic pain processing giving rise to chronic pain. Our model is consistent with a bulk of literature evidence, such as neuroimaging and pharmacological data collected on FM patients, and with correlations between FM and immunoendocrine conditions, such as stress, perimenopause, chronic inflammation, obesity, and chronic dizziness. The model suggests that critical targets for FM treatment are to be found among immunoendocrine pathways leading to GABA/glutamate imbalance having an impact on the thalamocortical system.

Prevalence of diabetic striatopathy and predictive role of glycated hemoglobin level.

BACKGROUND: Diabetic striatopathy is defined as a state of hyperglycemia associated with chorea/ballism, striatal hyperdensity at CT, or hyperintensity at T1-weighted MRI. It is considered a rare complication of uncontrolled diabetes but prevalence data are scarce. OBJECTIVES: Characterize diabetic striatopathy prevalence in the population afferent to the largest teaching hospital in Genova (Liguria, Italy) and investigate the role of glycated hemoglobin level in predicting the risk. METHODS: Data were retrospectively obtained from general population undergoing blood sampling for glycated hemoglobin and resulting with HbA1c values ≥ 8%, from January 2014 to June 2017. Brain neuroimaging of those who underwent at least a brain CT or MRI was examined in search of findings compatible with diabetic striatopathy and clinical information was collected. Logistic regression was used to predict the risk of diabetic striatopathy based on age and HbA1c values. RESULTS: Subjects with uncontrolled diabetes were 4603. Brain neuroimaging was available in 1806 subjects and three patients with diabetic striatopathy were identified, all of them reporting choreic movements. The prevalence of hemichorea due to diabetic striatopathy was therefore 3 cases out of 1806 (0.16%) in our population. Hepatic and hypoxic encephalopathies were the conditions most frequently mimicking diabetic striatopathy. Odds ratio of diabetic striatopathy and HbA1c level was significantly correlated (p = 0.0009). CONCLUSIONS: To the best of our knowledge, this study is the first to evaluate the prevalence of diabetic striatopathy in Italy. High HbA1c values may have a role in predicting diabetic striatopathy.

The value of EEG attenuation in the prediction of outcome in COVID-19 patients.

INTRODUCTION: During the COVID-19 pandemic, electroencephalography (EEG) proved to be a useful tool to demonstrate brain involvement. Many studies reported non-reactive generalized slowing as the most frequent pattern and epileptiform activity in a minority of patients. OBJECTIVE: To investigate the prevalence of diffuse unreactive background attenuation or suppression and its correlation with outcome in a cohort of COVID-19 patients. METHODS: The EEGs recorded during the first year of the COVID-19 pandemic were retrospectively evaluated to identify the main pattern and focus on the occurrence of a low-voltage background, either attenuated (10-20 µV) or suppressed (< 10 µV). We sought a correlation between in-hospital mortality and low-voltage EEG. In a subsample of patients, biomarkers of inflammation, hypoxemia and organ failure were collected. Brain imaging was also evaluated. RESULTS: Among 98 EEG performed in 50 consecutive patients, diffuse unreactive slowing was the most prevalent pattern (54%), followed by unreactive attenuation or suppression pattern (26%), being the latter significantly correlated with an unfavourable outcome (p = 0.0004). Survivors showed significantly lower interleukine-6 values compared to non-survivors. Patients with attenuated EEG and non-survivors also showed lower PaO2/FiO2 values. Neuroradiological findings were very heterogeneous with a prevalence of lesions suggestive of a microangiopathic substrate. CONCLUSIONS: EEG attenuation or suppression may be more frequent than previously reported and significantly associated with a poor outcome. SARS-CoV-2 infection may result in encephalopathy and reduced EEG voltage through mechanisms that are still unknown but deserve attention given its negative impact on prognosis.

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.

Dual task gait deteriorates gait performance in cervical dystonia patients: a pilot study.

Day-to-day walking-related activities frequently involve the simultaneous performance of two or more tasks (i.e., dual task). Dual task ability is influenced by higher order cognitive and cortical control mechanisms. Recently, it has been shown that the concomitant execution of an attention-demanding task affected postural control in subject with cervical dystonia (CD). However, no study has investigated whether dual tasking might deteriorate gait performance in CD patients. To investigate whether adding a concomitant motor and cognitive tasks could affect walking performance in CD subjects.17 CD patients and 19 healthy subjects (HS) participated in this pilot case-control study. Gait performance was evaluated during four walking tasks: usual, fast, cognitive dual task and obstacle negotiation. Spatiotemporal parameters, dual-task cost and coefficients of variability (CV%) were measured by GaitRite® and were used to detect differences between groups. Balance performance was also assessed with Mini-BEST and Four Step Square tests. In CD participants, correlation analysis was computed between gait parameters and clinical data. Significant differences in complex gait and balance performance were found between groups. CD patients showed lower speed, longer stance time and higher CV% and dual-task cost compared to HS. In CD, altered gait parameters correlated with balance performance and were not associated with clinical features of CD. Our findings suggest that complex walking performance is impaired in patients with CD and that balance and gait deficits might be related.

I can't count, but I can beat you playing cards: a case report on autoimmune encephalitis.

BACKGROUND: Autoimmune encephalitis (AE) is a rare inflammatory disorder characterized by important psychiatric and neurologic symptoms. The literature documents high rates of neuropsychological dysfunction in N-methyl D-aspartate-receptor (NMDAr) encephalitis but papers don't consider specifically calculation disturbances between the long-term deficits, although deficits in executive control and episodic memory were less likely to resolve. CASE REPORT: Here we present a severe case of NMDAr encephalitis in a young patient without a relevant past medical history. Upon first examination he presented psycho-motor slowdown, speech disorders, severe cognitive deficits in all areas: concentration, attention, memory, language, dual task functions, increased latency in responses, severe dyscalculia. Upon first evaluation, the young patient underwent a battery of neuropsychological tests and he showed a dysexecutive syndrome with performances significantly low for age and education. Our patient hence underwent 1 month of intensive cognitive rehabilitation. After the rehabilitation treatment, he presented an amelioration in all domains except calculations. CONCLUSIONS: In our patient the calculation disorder has proved to be the most relevant problem and the most difficult to treat. Clinicians should consider a careful approach to determine the prognosis of this syndrome because of the wide range of deficits, the need of prolonged treatment and the rate of long-term sequelae.

Effect of Short-Term Exposure to Supplemental Vibrotactile Kinesthetic Feedback on Goal-Directed Movements after Stroke: A Proof of Concept Case Series.

Many survivors of stroke have persistent somatosensory deficits on the contralesional side of their body. Non-invasive supplemental feedback of limb movement could enhance the accuracy and efficiency of actions involving the upper extremity, potentially improving quality of life after stroke. In this proof-of-concept study, we evaluated the feasibility and the immediate effects of providing supplemental kinesthetic feedback to stroke survivors, performing goal-directed actions with the contralesional arm. Three survivors of stroke in the chronic stage of recovery participated in experimental sessions wherein they performed reaching and stabilization tasks with the contralesional arm under different combinations of visual and vibrotactile feedback, which was induced on the ipsilesional arm. Movement kinematics were encoded by a vibrotactile feedback interface in two ways: state feedback-an optimal combination of hand position and velocity; and error feedback-the difference between the actual hand position and its instantaneous target. In each session we evaluated the feedback encoding scheme's immediate objective utility for improving motor performance as well as its perceived usefulness. All three participants improved their stabilization performance using at least one of the feedback encoding schemes within just one experimental session. Two of the participants also improved reaching performance with one or the other of the encoding schemes. Although the observed beneficial effects were modest in each participant, these preliminary findings show that supplemental vibrotactile kinesthetic feedback can be readily interpreted and exploited to improve reaching and object stabilizing actions performed with the contralesional arm after stroke. These short-term training results motivate a longer multisession training study using personalized vibrotactile feedback as a means to improve the accuracy and efficacy of contralesional arm actions after stroke.

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.

Epilepsy course during COVID-19 pandemic in three Italian epilepsy centers.

During epidemic outbreaks, epilepsy course can be modified by different physical and psychological stressors and, most importantly, by irregular therapy intake. The effect of COVID-19 and quarantine isolation on the course of epilepsy and on incidence of new-onset seizures is still unclear. With the aim of managing epilepsy in quarantined patients, three Italian Epilepsy Centers set up telephone consultations using a semistructured interview, allowing a prospective collection of data on seizure course and other seizure-related problems during pandemic. The collected data on seizure course were compared with the analogous period of 2019. The level of patients' concern relating to the COVID-19 pandemic was also assessed using a numeric rating scale. To address the effect of COVID-19 pandemic on seizure incidence, data collection included the number of consultations for first seizures, relapse seizures, and status epilepticus (SE) in the emergency department of one of the participating centers. Clinical telephone interviews suggest the absence of quarantine effect on epilepsy course in our cohort. No differences in incidence of emergency consultations for seizures over a two-month period were also observed compared with a control period. As demonstrated in other infective outbreaks, good antiepileptic drug (AED) supplying, precise information, and reassurance are the most important factors in chronic conditions to minimize psychological and physical stress, and to avoid unplanned treatment interruptions.

The Effect of Kinesio Taping on Spasticity: A Randomized, Controlled, Double-Blind Pilot Study in Para-Swimmers.

CONTEXT: Kinesio Taping (KT) produces several clinical effects, including pain relief, edema absorption, and improved muscle performance. When applied in the insertion to origin mode, it is claimed to inhibit excessive muscle contractions. OBJECTIVE: Investigate whether KT applied in the insertion to origin mode could reduce the exaggerated reflex contraction of spastic muscles. DESIGN: Randomized crossover trial, with a restricted block randomization. SETTING: Clinical laboratory and swimming pool. PATIENTS: Seven para-swimmers. INTERVENTION: KT, applied in inhibitory mode, to investigate its effect on knee extensor spasticity. MAIN OUTCOME MEASURES: Primary outcome is stretch reflex, as compared with clinical assessment of spasticity by Modified Ashworth Scale and self-perceived spasticity by numeric rating scale. Secondary outcomes were Medical Research Council for strength of knee extensor muscles and chronometric swimming performance in 100-m freestyle. RESULTS: KT significantly decreased the amplitude of stretch reflex (P < .001), whereas the placebo treatment produced no significant effects. Scores of Medical Research Council for strength and Modified Ashworth Scale did not change after KT, whereas numeric rating scale scores for spasticity significantly decreased (P = .001). The swimming performance was significantly improved after KT treatment as compared with baseline (P < .01). CONCLUSIONS: This exploratory study performed on para-athletes suggests that KT could reduce spasticity. This outcome has 3-fold implications for clinical, rehabilitation, and sport methods.

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.

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.

Protocol for the study of self-perceived psychological and emotional well-being of young Paralympic athletes.

BACKGROUND: We present the detailed protocol set up to investigate how agonistic sport affects the self-perceived psychological and emotional well-being of disabled young people. METHODS: The study will be carried out on a number of subjects as large as 800-1200, using well-established indices that give a quantitative measure of such well-being, namely SF-12 and PGWBI. The related questionnaires will be administered to the participants to a forthcoming international event, the European Para-Youth Games, 9-15 October 2017, Liguria, Italy, as well as to a reference population of a similar number of subjects, made up of young disabled people that do not practice agonistic sport. DISCUSSION: We expect that the outcomes of the study may strongly impact not only the socio-sanitary field but also society in general, as disabled people can be considered an extreme situation in the issue of balancing individual needs and environment to pursue psychological well-being. TRIAL REGISTRATION: ISRCTN14389453 (29 June 2017).

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.

Effects of continuous visual feedback during sitting balance training in chronic stroke survivors.

BACKGROUND: Postural control deficits are common in stroke survivors and often the rehabilitation programs include balance training based on visual feedback to improve the control of body position or of the voluntary shift of body weight in space. In the present work, a group of chronic stroke survivors, while sitting on a force plate, exercised the ability to control their Center of Pressure with a training based on continuous visual feedback. The goal of this study was to test if and to what extent chronic stroke survivors were able to learn the task and transfer the learned ability to a condition without visual feedback and to directions and displacement amplitudes different from those experienced during training. METHODS: Eleven chronic stroke survivors (5 Male - 6 Female, age: 59.72 ± 12.84 years) participated in this study. Subjects were seated on a stool positioned on top of a custom-built force platform. Their Center of Pressure positions were mapped to the coordinate of a cursor on a computer monitor. During training, the cursor position was always displayed and the subjects were to reach targets by shifting their Center of Pressure by moving their trunk. Pre and post-training subjects were required to reach without visual feedback of the cursor the training targets as well as other targets positioned in different directions and displacement amplitudes. RESULTS: During training, most stroke survivors were able to perform the required task and to improve their performance in terms of duration, smoothness, and movement extent, although not in terms of movement direction. However, when we removed the visual feedback, most of them had no improvement with respect to their pre-training performance. CONCLUSIONS: This study suggests that postural training based exclusively on continuous visual feedback can provide limited benefits for stroke survivors, if administered alone. However, the positive gains observed during training justify the integration of this technology-based protocol in a well-structured and personalized physiotherapy training, where the combination of the two approaches may lead to functional recovery.

Brain (18)F-DOPA PET and cognition in de novo Parkinson's disease.

PURPOSE: The role of mesocortical dopaminergic pathways in the cognitive function of patients with early Parkinson's disease (PD) needs to be further clarified. METHODS: The study groups comprised 15 drug-naive patients with de novo PD and 10 patients with essential tremor (controls) who underwent (18)F-DOPA PET (static acquisition, normalization on mean cerebellar counts) and an extended neuropsychological test battery. Factor analysis with varimax rotation was applied to the neuropsychological test scores, to yield five factors from 16 original scores, which explained 82 % of the total variance. Correlations between cognitive factors and (18)F-DOPA uptake were assessed with SPM8, taking age and gender as nuisance variables. RESULTS: (18)F-DOPA uptake was significantly lower in PD patients than in controls in the bilateral striatum, mainly in the more affected (right) hemisphere, and in a small right temporal region. Significant positive correlations were found only in PD patients between the executive factor and (18)F-DOPA uptake in the bilateral anterior cingulate cortex (ACC) and the middle frontal gyrus, between the verbal fluency factor and (18)F-DOPA uptake in left BA 46 and the bilateral striatum, and between the visuospatial factor and (18)F-DOPA uptake in the left ACC and bilateral striatum. No correlations were found between (18)F-DOPA uptake and either the verbal memory factor or the abstraction-working memory factor. CONCLUSION: These data clarify the role of the mesocortical dopaminergic pathways in cognitive function in early PD, highlighting the medial frontal lobe, anterior cingulate, and left BA 46 as the main sites of cortical correlation with executive and language functions.

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.

Patient With Rigidity and Fasciculations: Steroid-Responsive Presentation of Anti-IgLON5 Disease

An 82-year-old man presented with 2-year lasting widespread muscular fasciculations, cramps, and limb stiffness, with spontaneous movements in the right lower limb, unsteady gait (Video 1), and falls. Neurophysiologic studies disclosed signs of neuromuscular hyperexcitability. CSF analysis showed high tau protein concentration (543 pg/mL; reference values, <404) and unique-to-CSF oligoclonal bands. Serum and CSF anti-IgLON5 antibodies were positive (Figure 1). He carried the anti-IgLON5 disease-associated HLA-DRB1*10:01 allele.1 Brain MRI, thoracoabdominal CT, whole-body FDG-PET, and video-polysomnography were unremarkable. No sleep disturbances, bulbar symptoms, parkinsonism, or dementia were detected. Intravenous methylprednisolone (500 mg/d for 5 days), followed by oral benzodiazepines, prompted rapid functional recovery, with limb stiffness and gait improvement (Video 1), which persisted at 6-month follow-up. Anti-IgLON5 disease has progressive course and protean clinical presentations,2 representative, in our patient, for overlapping signs and symptoms of neuromuscular hyperexcitability and rigidity. Identification of rare phenotypes is important because prompt recognition and treatment can improve prognosis.