Mycosis fungoides: disease evolution of the "lion queen" revisited.

Mycosis fungoides (MF), which represents the most common subtype of primary cutaneous T-cell lymphoma (CTCL), is an epidermotropic lymphoma included as an indolent form in the recent WHO/EORTC classification. From a clinical point of view, the classic disease progression usually is slow and takes over years or even decades, and characterized by the evolution from patches to more infiltrated plaques and eventually to tumours or erythroderma. However, the analysis of the MF disease course has been greatly impaired by the rarity of the disease, thus data about the time course of disease progression and pattern of relapse during time are not well known. In this review, a summary of published data on MF large patients cohorts will be presented, together with the results obtained by a retrospective analysis of clinical features and follow-up data of 1,422 MF patients diagnosed and followed-up from 1975 to 2010 in 27 Italian Centres (Italian Study Group for Cutaneous Lymphoma). From a clinical perspective, the amount of data support the relevance of a stage-tailored, differentiated follow-up strategy, in as much as the TNMB staging appears not only to be associated with different progression rates, but also shows as a new finding a relationship with different patterns of disease progression. From a biological point of view, there is the need to understand the molecular basis of the different clinical pathways of disease progression, to be able to potentially identify at an earlier phase of disease evolution, the patients who are more likely to develop erythroderma or tumour-stage progression. In conclusion, if MF is indeed a true "lion queen", as dermatologists we need to be expert and wise tamers to keep it under control.

Abnormal plasticity of sensorimotor circuits extends beyond the affected body part in focal dystonia.

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

Motor cortical excitability studied with repetitive transcranial magnetic stimulation in patients with Huntington's disease.

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

No clinical or neurophysiological evidence of botulinum toxin diffusion to non-injected muscles in patients with hemifacial spasm.

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.

Neither simple nor sequential arm movements are bradykinetic in parkinsonian patients with peak-dose dyskinesias.

OBJECTIVE: To find out whether parkinsonian patients with levodopa-induced peak-dose dyskinesias are bradykinetic. METHODS: The performance of a sequential internally determined arm movement and a simple externally triggered arm movement was studied in a group of dyskinetic parkinsonian patients during their best clinical condition and when they were OFF treatment. Patients' performance was compared with that of an age-matched control group. Movements in the three-dimensional space were recorded by the ELITE motion analysis system. Kinematic variables analysed for the sequential motor task were total movement duration and total pause duration; for the simple motor task, movement duration and reaction time; and for both tasks, movement inaccuracy. RESULTS: When patients were OFF therapy they performed sequential and simple movement tasks slower than healthy subjects whereas when they were dyskinetic they did not. During the sequential task, when the patients were dyskinetic total pause duration shortened and movement inaccuracy increased. CONCLUSIONS: Our kinematic finding indicates that parkinsonian patients' with peak-dose dyskinesias are not bradykinetic. SIGNIFICANCE: Parkinsonian patients with peak-dose dyskinesias are not bradykinetic, probably because dopamine at peak doses functionally normalizes the mechanisms controlling movement speed.

Elevated vascular endothelial growth factor (VEGF) serum levels in idiopathic myelofibrosis.

An increase of angiogenesis has been shown in idiopathic myelofibrosis with myeloid metaplasia (MMM) by microvessel density count method but evaluation of circulating angiogenic factors is still incomplete. In 31 patients affected by MMM and in 12 healthy subjects we evaluated the serum levels of VEGF (vascular endothelial growth factor) and correlated VEGF with clinical and laboratory features of disease. We found that MMM patients had circulating VEGF concentrations much higher than controls (Median 1208 ng/ml vs 138 ng/ml, P < 0.0001). No correlation was found between VEGF and Hb, WBC, PLT, LDH, creatinine, bone marrow cellularity, fibrosis, splenomegaly, hepatomegaly, and therapy. However, in the subgroup of patients with a normal or low VEGF concentration, a direct correlation between VEGF and platelet count (r = 0.90, P = 0.002) was detected. Moreover, patients with a platelet count < 300 x 10(9)/l had VEGF serum levels lower than patients with a higher PLT count (median VEGF 864 vs 1557 pg/ml, P = 0.001). In six patients and in eight controls we also had the opportunity to measure VEGF in the plasma and we calculated that VEGF concentration was much higher in platelet-rich than in platelet-poor plasma and that platetets of MMM patients contained four times more VEGF than those of healthy controls. These results indicate that VEGF is overproduced in MMM, thus confirming an increased angiogenic activity. Platelets are probably a major source of VEGF in MMM but not the only one.

Sibling visiting in a neonatal intensive care unit.

The effect of sibling visiting in a neonatal intensive care unit was studied. Sixteen siblings of 13 infants were randomly assigned to a visiting or nonvisiting group. Behavioral patterns were measured by questionnaires administered to the parents and by direct observation and interviews with the children. There were no significant changes in the behavior of the children following the birth of their sibling, and there was no significant difference between the behavior scores of the two groups 1 week after the experimental (or control) intervention. The visiting children did not show signs of fear or anxiety during the visit. These data suggest that sibling visiting to a neonatal intensive care unit is not likely to be harmful and might be beneficial to the siblings and their families.

Infants weighing 1,000 grams or less at birth: developmental outcome for ventilated and nonventilated infants.

The neurodevelopmental outcome at a mean age of 40 months was investigated in 23/25 surviving infants of birth weights less than or equal to 1,000 gm. Eight infants required intubation and assisted ventilation and 17 were not ventilated. One ventilated infant was lost to follow-up and one nonventilated infant was a victim of sudden infant death syndrome at age 6 months. Fifteen (65%) had a good outcome but the differences between ventilated and nonventilated infants were striking. Thirteen (81%) of the nonventilated group were normal, but only two ventilated survivors (28%) were normal (P less than 0.05). Cicatricial retrolental fibroplasia occurred in three (43%) of the ventilated survivors and in none of the nonventilated infants (P less than .02). The requirement for assisted ventilation in these very low-birth-weight infants is associated with significant morbidity. Improvement in outcome may depend as much upon better understanding and management of prenatal events as upon improvements in neonatal care.

Different patterns of I-waves summation in ALS patients according to the central conduction time.

OBJECTIVES: To study facilitatory I-waves interaction, using two near threshold stimuli, to test both excitability and conductivity changes related to cortico-motoneuronal involvement in amyotrophic lateral sclerosis (ALS) patients in different stages of the disease. METHODS: Pairs of threshold magnetic stimuli were applied over the motor cortex at inter-stimulus intervals (ISI) ranging from 1-1.5 to 2.5-3 ms and from 4 to 4.5ms. The electromyogram responses were recorded from relaxed first dorsal interosseus (FDI). RESULTS: The data of I-waves summation were distributed according to the central conduction time (CCT) and all 3 peaks of facilitation were considered for statistical analysis. Patients with normal CCT showed a normal I-waves summation for the first peak, whilst patients with abnormal CCT had a significant reduction in facilitation (P<0.02). Six out of 11 patients with normal CCT had facilitation in the first peak, which exceeded 2 SD of normal values. CONCLUSIONS: In conclusion ALS patients showed two different and opposite patterns of I-waves summation which could be related to different stages of the disease.

Diagnostic importance of combined parent and teacher ratings on the Revised Behavior Problem Checklist.

The Revised Behavior Problem Checklist (RBPC) was completed by parents and teachers for 105 child psychiatry outpatient boys aged 6 to 12 years. In addition, DSM-III diagnoses were determined independent of checklist results, and the children were divided into major diagnostic groups of externalizing, internalizing, and mixed disorders. Combined parent and teacher ratings proved more effective than separate ratings in distinguishing the externalizing and mixed groups from the internalizing group on the RBPC externalizing factors. The overall classification of individual boys with discriminant function analysis increased from 72% to 83% when the ratings of both parents, rather than one parent, were combined with teacher ratings. Enhancing diagnostic accuracy of type of psychiatric disorder by using combined parent and teacher behavior checklist ratings is discussed.

Collaboration and teamwork in assessment for early intervention.

Interdisciplinary teamwork and collaboration in early intervention require that professionals adopt a common set of developmentally appropriate standards that guide the major activities of screening, diagnostic assessment, individualized curriculum planning, progress and program evaluation, and family-centered services. This article has reviewed the common roadblocks to effective teamwork, especially among educational and medical professionals. As solutions to the typical problems in collaboration, eight developmentally appropriate standards ensure best practice and adherence to the Individuals with Disabilities Education Act mandates: utility, acceptability, authenticity, equity, sensitivity, convergence, congruence, and collaboration.

Evaluation of leg joint trajectories while carrying out passive manipulation by NEUROBike.

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.

Prognostic value of standard EEG in traumatic and non-traumatic disorders of consciousness following coma.

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

Transcranial magnetic stimulation as trigger of dystonic attacks in a patient affected by paroxysmal kinesigenic dyskinesia.

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.

One-hertz subthreshold rTMS increases the threshold for evoking inhibition in the human motor cortex.

Despite indisputable evidence that repetitive transcranial magnetic stimulation (rTMS) modulates motor cortical excitability, the effects of subthreshold low-frequency rTMS on intracortical inhibition (ICI) are controversial. In this paper we investigated whether increasing the level of baseline ICI increases the sensitivity of ICI for disclosing the after-effects of rTMS on cortical excitability. In experiment 1, we studied changes in ICI, tested at two different baseline levels, after a train of 900 subthreshold rTMS pulses delivered at 1 Hz. In experiment 2, we studied whether the same conditioning rTMS train changed the ICI threshold, and in experiment 3 whether it changed the facilitatory I-wave interaction. Conditioning rTMS reduced ICI tested at a baseline level of 75% but left ICI tested at a baseline level of 50% unchanged. It also increased the ICI threshold but left the facilitatory I-wave interaction unchanged. These findings suggest that conditioning rTMS selectively reduced ICI tested at a baseline level of 75% by increasing the threshold for evoking inhibition in the motor cortex. The inhibitory system mediating ICI may therefore be more efficient than other motor cortical systems in reducing high cortical excitability after external intervention. Hence studies investigating the after-effects of rTMS should standardize ICI levels at baseline.

Do actions speak louder than words? The case of the disappearance of social communication oddities.

Within the last decade, researchers and clinicians have reported an increase in the incidence and diagnosis of Autism Spectrum Disorder (ASD). Various factors have been proposed for this apparent change including broader diagnostic criteria, greater public awareness, biological and environmental interactions, and earlier detection. However, it has been observed in a certain percentage of children, during the toddler and preschool years and before intervention is introduced, that severe language deficits distort social and self-regulatory behavior to such a degree that they mimic the characteristics of ASD. Professional caution is vital in this regard to describe early functioning and to defer diagnosis until the effects of intervention and treatment can be monitored over time. The case of Nicole, a preschooler with developmental delays and social communication oddities, illustrates what I believe is the most professionally responsible, cautious, family-centered, and data-based diagnostic process that links assessment, intervention, and evaluation for young children with early developmental difficulties.

Segmental myoclonus in a patient affected by syringomyelia.

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.

Modification of cortical excitability induced by gabapentin: a study by transcranial magnetic stimulation.

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.