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Chiari I malformation is accompanied by a variety of symptoms and signs suggesting brain stem, cerebellar, or cervical spinal cord lesions. The most common symptoms include headache, neck pain, sensory loss, and ataxia. Dysphagia occurs in 5-15% of the patients and it may be the only presenting symptom. Progressive dysphagia caused by Chiari I malformation, mimicking amyotrophic lateral sclerosis, has been reported in the "Journal of Neurology, Neurosurgery and Psychiatry" in 1996 and 2002. Dysphonia may occur rarely, but it has not been described as an early symptom. Pain and stiffness in the posterior neck is a common feature, but severe neck extensor weakness leading to dropped head syndrome has not so far been reported in Chiari I malformation.

Background: Primary late-onset focal dystonias may spread over time to adjacent body regions, but differences in the risk of spread over time among the various focal forms and the influence of age at dystonia onset on the risk of spread are not well established. Methods: Patients presenting with primary late-onset focal blepharospasm (BSP, n = 124), cervical dystonia (CD, n = 73) and focal hand dystonia (FHD, n = 24) with 10 years or more of disease duration (mean ± SD, 15.3 (SD 4.9) years) were included in the study. The relationship between demographic/clinical variables and spread of dystonia was assessed by Kaplan-Meier survival curves and Cox proportional hazard regression models. Results: Patients starting with BSP, CD and FHD had similar age, sex and disease duration. Age at dystonia onset, age at initial spread and the risk of initial spread were significantly higher, whereas time elapsing from onset to initial spread was significantly lower in the BSP group than in those with onset in the neck or in the upper extremities. Conversely, these parameters were similar in the CD and FHD groups. The greater risk of spread in the BSP group was mainly evident in the first 5 years of history; thereafter, it declined and became similar to that of patients with CD/FHD. The difference in the risk of initial spread by site of onset was partly confounded by age at dystonia onset. Site of and age at dystonia onset, and age at first spread, were not significant predictors of the risk of a second spread. Conclusion: This study adds new insights into the phenomenon of spread of primary late-onset focal dystonia and provides the framework for future studies aimed at an indepth investigation of the mechanism(s) of spread. [ABSTRACT FROM AUTHOR]

Abstract: We investigated the relationship between somatic and autonomic neuropathy in 40 chronic alcoholics. Electromyographic and neurographic studies of upper and lower limbs and a battery of six cardiovascular reflex tests were carried out. A score for somatic or autonomic neuropathy was calculated. All parameters were investigated for possible relationship with total life dose (TLD) of alcohol intake. Somatic neuropathy was detected in 25 patients (62.5%) and autonomic neuropathy in 13 patients (32.5%). Nineteen patients (47.5%) presented only a somatic neuropathy, six patients (15%) had only an autonomic neuropathy, and seven (17.5%) had a combined somatic and autonomic neuropathy. TLD was significantly higher in the group of patients with combined neuropathy than in the group with isolated somatic neuropathy. There was no significant correlation between laboratory parameters of somatic and autonomic neuropathy. Our findings do not support the existence of a parallel involvement of peripheral somatic and autonomic cardiovascular nerve fibers in chronic alcoholism. [Copyright &y& Elsevier]

In March 2020, WHO declared Covid-19 outbreak pandemic. There has been increasing evidence that frail, old, multi-pathological patients are at greater risk of developing severe Covid-19 infection than younger, healthy ones. Covid-19's impact on Parkinson's Disease (PD) patients could be analysed through both the influence on PD patients' health and their risk of developing severe Covid-19, and the consequences of lockdown and restrictive measures on mental and cognitive health on both patients and caregivers. Moreover, there are critical issues to be considered about patients' care and management through an unprecedented time like this. One important issue to consider is physiotherapy, as most patients cannot keep exercising because of restrictive measures which has profoundly impacted on their health. Lastly, the relationship between PD and Sars-Cov2 may be even more complicated than it seems as some studies have hypothesized a possible Covid-19-induced parkinsonism. Hereby, we review the state of the art about the relationship between Covid-19 and Parkinson's Disease, focusing on each of these five points. [ABSTRACT FROM AUTHOR]

• 5-Hz rPAS 25ms produces a long-lasting increase in corticospinal excitability. • 5-Hz rPAS 15ms effectively suppresses corticospinal excitability. • 5-Hz rPAS induces spike-timing dependent plasticity-like bidirectional plasticity. Sub-motor threshold 5 Hz repetitive paired associative stimulation (5 Hz-rPAS 25ms) produces a long-lasting increase in corticospinal excitability. Assuming a spike-timing dependent plasticity-like (STDP-like) mechanism, we hypothesized that 5 Hz-rPAS at a shorter inter-stimulus interval (ISI) of 15 ms (5 Hz-rPAS 15ms) would exert a lasting inhibitory effect on corticospinal excitability. 20 healthy volunteers received two minutes of 5 Hz-rPAS 15ms. Transcranial magnetic stimulation (TMS) was applied over the motor hotspot of the right abductor pollicis brevis muscle at 90% active motor threshold. Sub-motor threshold peripheral electrical stimulation was given to the left median nerve 15 ms before each TMS pulse. We assessed changes in mean amplitude of the unconditioned motor evoked potential (MEP), short-latency intracortical inhibition (SICI), intracortical facilitation (ICF), short-latency afferent inhibition (SAI), long-latency afferent inhibition (LAI), and cortical silent period (CSP) before and for 60 minutes after 5-Hz rPAS 15ms. Subthreshold 5-Hz rPAS 15ms produced a 20–40% decrease in mean MEP amplitude along with an attenuation in SAI, lasting at least 60 minutes. A follow-up experiment revealed that MEP facilitation was spatially restricted to the target muscle. Subthreshold 5-Hz rPAS 15ms effectively suppresses corticospinal excitability. Together with the facilitatory effects of subthreshold 5-Hz rPAS 25ms (Quartarone et al., J Physiol 2006;575:657–670), the results show that sub-motor threshold 5-Hz rPAS induces STDP-like bidirectional plasticity in the motor cortex. The results of the present study provide a new short-time paradigm of long term depression (LTD) induction in human sensory-motor cortex. [ABSTRACT FROM AUTHOR]

The relation between age at dystonia onset and sex was investigated in 264 patients with cranial-cervical dystonia and 56 patients with upper limb dystonia. In cranial-cervical dystonia, women had a significantly greater age at the onset of dystonia than men. The association was independent of duration of disease and distance of referral, but it was no longer detectable after adjustment for educational level. In upper limb dystonia, men and women did not differ for age at dystonia onset, duration of disease, education level, or distance of referral. A significant inverse association between age at the onset of dystonia and education was observed in both cranial-cervical dystonia and upper limb dystonia series. [ABSTRACT FROM AUTHOR]

The relation between age at dystonia onset and sex was investigated in 264 patients with cranial-cervical dystonia and 56 patients with upper limb dystonia. In cranial-cervical dystonia, women had a significantly greater age at the onset of dystonia than men. The association was independent of duration of disease and distance of referral, but was no longer detectable after adjustment for educational level. In upper limb dystonia, men and women did not differ for age at dystonia onset, duration of disease, education level, or distance of referral. A significant inverse association between age at the onset of dystonia and education was observed in both cranial-cervical dystonia and upper limb dystonia series. [ABSTRACT FROM AUTHOR]

Background. Surround inhibition is a system that sharpens sensation by creating an inhibitory zone around the central core of activation. In the motor system, this mechanism probably contributes to the selection of voluntary movements, and it seems to be lost in dystonia. Objectives. To explore if sensory information is abnormally processed and integrated in focal hand dystonia (FHD) and if surround inhibition phenomena are operating during sensory-motor plasticity and somatosensory integration in normal humans and in patients with FHD. Methods. We looked at the MEP facilitation obtained after 5 Hz repetitive paired associative stimulation of median (PAS M), ulnar (PAS U), and median + ulnar nerve (PAS MU) stimulation in 8 normal subjects and 8 FHD. We evaluated the ratio MU/(M + U) ∗ 100 and the spatial and temporal somatosensory integration recording the somatosensory evoked potentials (SEPs) evoked by a dual nerve input. Results. FHD had two main abnormalities: first, the amount of facilitation was larger than normal subjects; second, the spatial specificity was lost. The MU/(M + U) ∗ 100 ratio was similar in healthy subjects and in FHD patients, and the somatosensory integration was normal in this subset of patients. Conclusions. The inhibitory integration of somatosensory inputs and the somatosensory inhibition are normal in patients with focal dystonia as well as lateral surrounding inhibition phenomena during sensory-motor plasticity in FHD. [ABSTRACT FROM AUTHOR]

Much evidence suggests that restless legs syndrome (RLS) is a disorder characterized by an unsuppressed response to sensory urges due to abnormalities in inhibitory pathways that specifically link sensory input and motor output. Therefore, in the present study, we tested sensory-motor integration in patients with RLS, measured by short latency afferent inhibition (SAI) and long latency afferent inhibition (LAI). SAI and LAI were determined using transcranial magnetic stimulation before and after 1month of dopaminergic treatment in RLS patients. Ten naïve patients with idiopathic RLS and ten healthy age-matched controls were recruited. Patients with secondary causes for RLS (e.g. renal failure, anaemia, low iron and ferritin) were excluded, as well as those with other sleep disorders. Untreated RLS patients demonstrated deficient SAI in the human motor cortex, which proved revertible toward normal values after dopaminergic treatment. We demonstrated an alteration of sensory-motor integration, which is normalized by dopaminergic treatment, in patients affected by RLS. It is likely that the reduction of SAI might contribute significantly to the release of the involuntary movements and might account for the sensory urge typical of this condition. [ABSTRACT FROM AUTHOR]

Background and purpose: Despite the growing number of reports describing adult-onset primary lower limb dystonia (LLD) this entity has never been systematically evaluated in the general population of patients with primary adult-onset dystonia. Methods: From outpatients with adult-onset primary dystonia attending nine Italian University centres for movement disorders we consecutively recruited 579 patients to undergo a standardized clinical evaluation. Results: Of the 579 patients assessed, 11 (1.9%) (8 women, 3 men) had LLD, either alone ( n = 4, 0.7%) or as part of a segmental/multifocal dystonia ( n = 7, 1.2%). The age at onset of LLD (47.9 ± 17 years) was significantly lower than the age at onset of cranial dystonias (57.9 ± 10.7 years for blepharospasm, and 58.9 ± 11.8 years for oromandibular dystonia) but similar to that of all the other adult-onset primary dystonias. The lower limb was either the site of dystonia onset (36.4%) or the site of dystonia spread (63.6%). In patients in whom LLD was a site of spread, dystonia seemed to spread following a somatotopic distribution. Only one patient reported a recent trauma involving the lower limb whereas 36.4% of the patients reported pain at the site of LLD. Only 64% of our patients needed treatment for LLD, and similarly to previously reported cases, the most frequently tried treatments was botulinum toxin and trihexyphenidyl. Conclusion: The lower limb is an uncommon but possible topographical site of dystonia in adulthood that should be kept in consideration during clinical evaluation. [ABSTRACT FROM AUTHOR]

Dystonia is characterized by two main pathophysiological abnormalities: ‘reduced’ excitability of inhibitory systems at many levels of the sensorimotor system, and ‘increased’ plasticity of neural connections in sensorimotor circuits at a brainstem and spinal level. A surprising finding in two recent papers has been the fact that abnormalities of inhibition similar to those in organic dystonia are also seen in patients who have psychogenic dystonia. To try to determine the critical feature that might separate organic and psychogenic conditions, we investigated cortical plasticity in a group of 10 patients with psychogenic dystonia and compared the results with those obtained in a matched group of 10 patients with organic dystonia and 10 healthy individuals. We confirmed the presence of abnormal motor cortical inhibition (short-interval intracortical inhibition) in both organic and psychogenic groups. However, we found that plasticity (paired associative stimulation) was abnormally high only in the organic group, while there was no difference between the plasticity measured in psychogenic patients and healthy controls. We conclude that abnormal plasticity is a hallmark of organic dystonia; furthermore it is not a consequence of reduced inhibition since the latter is seen in psychogenic patients who have normal plasticity. [ABSTRACT FROM PUBLISHER]

Background and purpose: Adult-onset dystonia may be related, amongst other factors, to abnormal neuronal plasticity in cortical and subcortical structures. Brain-derived neurotrophic factor is a major modulator of synaptic efficiency and neuronal plasticity. Recent works documented that a single nucleotide polymorphism (SNP) of the BDNF gene, the Val66Met SNP, modulates short-term plastic changes within motor cortical circuits. In this study we aimed at exploring the effect of this SNP upon the risk of developing common forms of primary adult-onset dystonia. Methods: We explored the influence of the Val66Met SNP of the BDNF gene on the risk of cranial and cervical dystonia in a cohort of 156 Italian patients and 170 age- and gender-matched healthy control subjects drawn from the same population. Results: The presence of the rare Met allele was not significantly associated with the diagnosis of dystonia (age- and gender-adjusted odds ratios of 1.22, P = 0.38). The study had a >90% power to detect a 50% change in the risk of developing cranial-cervical dystonia associated with the presence of the Met allele. Moreover, there was no relationship between Val66Met SNP and age at dystonia onset or type of dystonia. Conclusion: Our data do not support the common variant Val66Met of the BDNF gene as an etiologic factor shared by the various forms of primary adult-onset dystonia. [ABSTRACT FROM AUTHOR]

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 mm (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. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is characterized by chronic inflammation and demyelination of the central nervous system (CNS). Accumulating data indicate that oxidative stress, leading to reactive oxygen species (ROS) production and lipid peroxidation, as well as elevated levels of advanced glycation end products (AGE) in CNS neurons, might play a pivotal role in the pathogenesis of a number of diseases with a neurodegenerative aspect, such as MS. Therefore, polymorphisms of genes encoding endogenous free-radical scavenging systems, such as paraoxonase 1 (PON1), and anti-glycation defences, such as glyoxalase I (GI), could influence susceptibility to MS. In the present study, we have undertaken a case-control study to investigate the possible association of GI A111E, PON1 Q192R and L55M polymorphisms with the risk of MS. The three polymorphisms were characterized in 209 patients with relapsing-remitting MS (RRMS) and in 213 healthy controls by PCR/RFLP methods using DNA from lymphocytes. We found that individuals with the GI/AE-EE genotypes and PON55/LM-MM genotypes had a significantly higher risk of MS compared with the other genotypes. The two polymorphisms appear to be common genetic traits that are associated with an increased risk for MS - the analysis of both, in each single case, may be a revealing predictable factor for MS risk. [ABSTRACT FROM AUTHOR]

Background: The relationship between prior trauma and primary adult-onset dystonia is not well understood. Previous uncontrolled observations and exploratory case-control studies have yielded contradictory results.Objective: To analyse the association between cranial dystonia and prior head trauma.Methods: An ad hoc multicentre case-control study was performed using a semistructured interview to collect detailed information on the history of head trauma before disease onset in five Italian tertiary referral centres for movement disorders. The presence of a history of head trauma and of post-traumatic sequelae (loss of consciousness, bone fractures, scalp/facial wounds) before disease onset was recorded from 177 patients with primary adult-onset cranial dystonia and from 217 controls with primary hemifacial spasm matched by age strata and sex. Differences between groups were assessed by Mann-Whitney U test and Fisher's exact test, and the relationship between prior head trauma and case/control status was analysed by multivariate logistic regression models.Results: No association was found between vault/maxillofacial trauma and cranial dystonia. Most reported traumas occurred several years before disease onset. None of the main post-traumatic sequelae altered the chance of developing cranial dystonia compared with patients with primary hemifacial spasm, nor did head trauma modify the age at onset of cranial dystonia.Conclusions: These results do not support prior head trauma as a possible environmental factor modifying the risk of developing late-onset cranial dystonia. The lack of association may have pathogenetic and medical-forensic implications. [ABSTRACT FROM AUTHOR]

Cognitive dysfunction is considered one of the clinical markers of multiple sclerosis (MS). However, in the literature there are inconsistent reports on the prevalence of cognitive dysfunction, and separate data for the relapsing-remitting (RR) type of the disease are not always presented. In this study, we submitted 461 RRMS patients to a battery of neuropsychological tests to investigate their impairment in various cognitive domains. As a consequence of the exclusion criteria, the sample is not fully representative of the entire population of RRMS patients. In this selected sample, when only the eight scores of a core battery (Mental Deterioration Battery) were considered (with respective cutoffs), it emerged that 31% of the patients were affected by some degree of cognitive deficit. In particular, 15% had mild, 11.2% moderate and 4.8% had severe impairment. Information processing speed was the most frequently impaired area, followed by memory. When two other tests (SDMT and MCST) were added and cognitive domains were considered, it emerged that 39.3% of the patients were impaired in two or more domains. When four subgroups were obtained by means of cluster analysis and then compared, it emerged that information processing speed and memory deficits differentiated the still cognitively unimpaired from the mildly impaired MS patients. Significant associations were found between cognitive and clinical characteristics. However, due to the large sample size, clinically irrelevant relationships may also have emerged. Even with the limitations imposed by the sample selection and the possible underestimation of the prevalence and severity of cognitive dysfunction, these results seem to provide further evidence that information processing speed deficit may be an early and important marker of cognitive impairment in MS patients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Limb-girdle myasthenia is an uncommon disease and includes familial and autoimmune forms. Patients present proximal muscle weakness and wasting, and sometimes fatigability, without cranial nerve involvement and fluctuations. We observed, during a 15-year period, nine subjects with limb-girdle myasthenia, (24–55 years; 8 males, 1 female) who constituted 3.2% of 281 myasthenic patients attending our department. All had previously received a diagnosis different from myasthenia. Diagnosis of limb-girdle myasthenia was established by clinical, muscle biopsy and electrophysiological assessment including repetitive nerve stimulation and single fiber electromyography. Five patients had the familial form with tubular aggregates in skeletal muscle; four patients had the autoimmune form. Patients with the familial form had a good response to acetylcholinesterase inhibitors, and the patients with the autoimmune form responded to immunotherapy. Our findings reinforce the opportunity to suspect limb-girdle myasthenia in unclassifiable proximal myopathies and to differentiate familial from autoimmune cases, especially for therapeutic implications. [Copyright &y& Elsevier]

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 4.5 ms. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Wound botulism is a rare infectious disease that is becoming a frequent complication of parental drug use. Diagnosis is often difficult and based on clinical suspicion. We report the first Italian case of wound botulism due to intramuscular heroin injection in a 48-year-old man with an acute onset of slurred speech and dysphagia. The most considerable finding of electrophysiological study was the reduction in amplitude of compound muscle action potential which should be considered a useful initial electrodiagnostic sign in the clinical context of botulism. Alerting clinicians to botulism is crucial for a rapid diagnosis and appropriate treatment and thus decreasing mortality and complications. [ABSTRACT FROM AUTHOR]

Prior coffee and smoking habits were investigated in a multicentre case control study involving 166 patients presenting with primary late onset blepharospasm (BSP), 228 hospital control patients with primary hemifacial spasm and 187 population control subjects from five Italian centres. Information on age at disease onset, smoking and coffee drinking status at the reference age and average number of cups of coffee drunk/cigarettes smoked per day reached high and similar test-retest reproducibility in case and control patients. Unadjusted logistic regression analysis yielded a significant inverse association of prior coffee drinking and cigarette smoking with case status for the control groups. After adjustment for age, sex, referral centre, disease duration, years of schooling and ever coffee drinking/cigarette smoking, as appropriate, the smoking estimate lacked significance whereas the association of coffee intake and BSP did not (cases vs hospital control patients: OR 0.37 (95% CI 0.20 to 0.67); cases vs population control subjects: OR 0.44 (95% CI 0.23 to 0.85)). The strength of the inverse association between BSP and coffee intake tended to increase with the average number of cups drunk per day. There was a significant correlation between age of BSP onset and number of cups per day (adjusted regression coefficient 1.73; p = 0.001) whereas no correlation was found with number of packs of cigarettes per day. Coffee drinking may be inversely associated with the development of primary BSP and this association may partly depend on the amount consumed. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Although there is recent evidence for the role of intraoperative neurophysiological monitoring (IONM) in spine surgery, there are no uniform opinions on the optimal combination of the different tools. We analyzed the impact of the multimodal IONM (mIONM) on the preservation of neuronal structures and on functional restoration in a prospective series of our patients who underwent spine surgery. The mIONM approach in spine surgery involves the evaluation of somatosensory evoked potentials (SEPs) and motor evoked potentials (MEPs) with electrical transcranial stimulation, including the use of a multipulse technique with multiple myomeric registration of responses from limbs, and a single-pulse technique with D-wave registration through epi- and intradural recording, and free running and evoked electromyography. We observed an improvement of neurological status in 50% of the patients. The D-wave registration was the most useful intraoperative tool, especially when MEP and SEP responses were absent or poorly recordable. Our preliminary data confirm that mIONM plays a fundamental role in the identification and functional preservation of the spinal cord and nerve roots. It is highly sensitive and specific for detecting and avoiding neurological injury during spine surgery and represents a helpful tool for achieving optimal postoperative functional outcome. [ABSTRACT FROM AUTHOR]

Surround inhibition is a system that sharpens sensation by creating an inhibitory zone around the central core of activation. In the motor system, this mechanism probably contributes to the selection of voluntary movements and seems to be lost in dystonia. To explore if sensory information is abnormally processed and integrated in focal dystonia and if surround inhibition phenomena are operating during sensory-motor plasticity and sensory-motor integration in normal humans and in patients with focal hand dystonia. We looked at motor evoked potential (MEP) facilitation, in the APB and ADM muscles, obtained after 5 Hz repetitive paired associative stimulation, stimulating median (PAS M), ulnar (PAS U) and median + ulnar nerve (PAS MU) in 8 normal subjects and 8 dystonic patients. We evaluated the ratio MU/(M + U) × 100. Moreover, we tested the spatial and temporal somatosensory integration recording SEPs evoked by a dual nerve input. Our data confirmed that in dystonic patients the amount of facilitation was larger than normal subjects and the spatial specificity was lost. The MU/(M + U) × 100 ratio was similar in healthy subjects and in dystonic patients and the somatosensory integration was normal in this subset of patients. These data suggest that lateral surround inhibition phenomena during sensory-motor plasticity are normal in focal hand dystonia. [ABSTRACT FROM AUTHOR]

Glycogen storage disease II (GSD II), also known as Pompe disease is an autosomal recessive disorder caused by mutations in the GAA gene encoding the enzyme acid alpha-glucosidase. Two different clinical forms have been described: infantile (IOPD) and late-onset (LOPD). Aim of the study is to evaluate EMG findings, in particular distal muscle involvement, in a cohort of LOPD patients. 15 LOPD patients (9 Male–6 Female) underwent to ENG and EMG evaluation looking at spontaneous activity, MUP analysis recruitment. EMG evidenced the presence of myotonic discharges (MD) in paraspinal muscles in 6 patients and in distal limb muscles in 1 patient. Fibrillation potentials occurred in all muscles where MD were found. Short duration, MUPs were found in the paraspinal (6/12), proximal (6/12) and distal limb muscles (5/12). Our results confirm that myopathic EMG pattern is usually observed in proximal muscles, but we also find a similar pattern in distal muscles revealing a subclinical involvement. Moreover, myotonic discharges and denervation activity are present in both paraspinal and distal muscles. We can conclude that it is useful to extend the EMG study also to distal muscles even if not clinically compromised. [ABSTRACT FROM AUTHOR]

Thyroid hormone resistance describes a rare syndrome in which the thyroid hormone levels are elevated, but the thyroid stimulating hormone level is not suppressed. The importance of thyroid hormones in brain normal function is corroborated by the frequent association of thyroid dysfunctions with neurological and psychiatric symptoms. In this study, we investigated whether adult thyroid hormone resistance affects cortical excitability and modulates inhibitory and excitatory intracortical circuitries. Cortical excitability was probed with transcranial magnetic stimulation in 6 patients with thyroid hormone resistance, 10 patients affected by hypothyroidism, and 10 age-matched healthy controls. We tested motor thresholds, motor evoked potential recruitment curve, cortical silent period, intracortical inhibition, and intracortical facilitation. Patients with thyroid hormone resistance showed decreased steepness of the motor evoked potential recruitment curves. These changes were paralleled by shorter cortical silent period and increased intracortical inhibition. In conclusion, thyroid hormones may influence cortical excitability and cortical inhibitory circuits in adults. [ABSTRACT FROM AUTHOR]

Repetitive transcranial magnetic stimulation (rTMS) affects neuronal plasticity in humans and animals, even if the molecular mechanisms underlying rTMS effects are still not clear. In this study we examined whether low and high frequency rTMS may be neuroprotective. To achieve this aim, we determined Bcl-2/Bax expression in the prefrontal cortex of rats treated with 1 Hz or 5 Hz rTMS for five consecutive days. In addition, we examined CaMKII α and CREB brain plasticity related proteins and their role in regulating Bcl-2/Bax. We found that both 1 Hz and 5 Hz rTMS increase Bcl-2, CaMKII α and CREB expression. Our results suggest that both 1 and 5 Hz rTMS treatment for 5 days may produce neuroprotective effects by increasing expression of neuroprotective Bcl-2. This rTMS- induced Bcl-2 synthesis is likely mediated by the heightened activation and expression of CaMKII α - and CREB. [ABSTRACT FROM AUTHOR]

Cervical dystonia (CD) is one of the most common forms of primary dystonia. The pathogenesis of the disease is still unknown, although evidence suggests a role for genetic factors. Recently, a polymorphism in the dopamine D5 receptor (DRD5) gene has been associated with the disease in a British population, suggesting that DRD5 is a susceptibility gene for CD. To confirm these data, we performed a case-control study of the microsatellite (CT/GT/GA)(n) at the DRD5 locus in 104 Italian CD patients and 104 healthy controls. The frequency of allele 4 was higher in the CD patients compared to the controls. This resulted in a twofold increased risk of developing the disease. These results provide further evidence of an association between DRD5 and cervical dystonia, supporting the involvement of the dopamine pathway in the pathogenesis of CD. [ABSTRACT FROM AUTHOR]

In this study we investigated cortical excitability, inhibitory and excitatory intracortical circuitries, by using transcranial magnetic stimulation, in both hemispheres of patients affected by brain tumors. Cortical excitability was probed with transcranial magnetic stimulation in 10 right-handed patients (3 women), aged 49–70 years (mean age: 54.8 years) and 10 age-matched healthy controls. We tested motor thresholds (MT), motor evoked potential (MEP) recruitment curve, cortical silent period (CSP), short and long intracortical inhibition (SICI and LICI), intracortical facilitation (ICF), short and long afferent inhibition (SAI and LAI) and inter-hemispheric inhibition (IHI). RMT and AMT were higher in both hemispheres of patients with brain tumors than healthy controls. The slope of MEP recruitment curve was deeper in both hemispheres of patients with brain tumors. SICI, LICI, SAI and LAI are reduced in patients with brain tumors compared with aged matched healthy controls. Cortical excitability, specially inhibitory intracortical circuitries, are impaired in both hemispheres of patients affected by brain tumors. [ABSTRACT FROM AUTHOR]

To evaluate the effects of a brief PAS on the corticospinal excitability on M1, observing the modulation of the MEP amplitude and of the absolute EEG-power, and their correlations, as expression of cortical synaptic strengthening/weakening. We tested on 12 healthy subjects the effect of three PAS conditioning protocols (25 ms, 15 ms and sham ISI) on the MEP amplitude and the absolute EEG-power, and their specific correlations, 30’ after the end of the protocols. We found after PAS25ms a MEP amplitude increase correlated to a global reduction in α / β -EEGpower and increase in θ / δ . After PAS15ms a MEP amplitude decrease correlated to a global increase in α / β -EEGpower and reduction in θ / δ . No changes were found after rPASsham. Looking at these modulations and correlations, it is conceivable that the effects of PAS25ms could be expression of cortical synaptic potentiation. On the contrary the effects of PAS15ms could mean cortical reset. The modulation could be dependent from cortical GABAergic, glutamatergic and cholinergic circuitries. Beyond the purely neurophysiological aspects, our protocol could be interesting in neuro-rehabilitation, taking account of the effective, quick and persistent modulation of cortical oscillatory activity at bi-hemispheric level. [ABSTRACT FROM AUTHOR]

Aim of the present study was to investigate motor cortex synaptic plasticity in both hemispheres of patients affected by brain tumors. We employed an electrophysiological protocol, named repetitive paired associative stimulation (rPAS), involving repetitive transcranial magnetic stimulation (rTMS) paired with electrical stimulation of the contralateral median nerve, that modifies cortico-spinal excitability. Ten right-handed patients (3 women), aged 49–70 years (mean age: 54.8 years), participated in the study. Motor evoked potentials (MEP) were measured at baseline before and for up to 30 min after 5 Hz-rPAS in abductor pollicis brevis (APB). rPAS consisted of 600 pairs of transcranial magnetic stimuli, at a rate of 5 Hz for 2 min, coupled with electrical median nerve stimulation preceding TMS over the contralateral M1 at an interstimulus interval of 25 ms. In both hemispheres of patient with brain tumors rPAS did not induce any significant changes in MEP amplitudes, compared with aged matched healthy controls. Synaptic plasticity is impaired in both hemispheres of patients affected by brain tumors. [ABSTRACT FROM AUTHOR]

We have recently demonstrated an increased BDNF-TrkB signaling and TrkB-NMDA receptor coupling after consecutive 5days high frequency (5Hz) rTMS in rat brain prefrontal cortex and lymphocytes, and similar results were obtained from lymphocytes of healthy human subjects. In the present study, we have investigated whether rTMS could produce modifications in the activation of down-stream long-term effects regulatory molecules such as CaMKIIα and CREB in rat prefrontal cortex and in lymphocytes. We treated 6 normal Sprague–Dawley rats with 5days chronic low (1Hz) and high (5Hz) frequency rTMS in separate groups. After that we measured the CaMKIIα and CREB expressions in prefrontal cortex and in lymphocytes. We found that both low- and high-frequency rTMS significantly increased CaMKIIα and CREB expressions in prefrontal cortex. High-frequency rTMS stimulated expression was found to be increased more than low-frequency. In lymphocytes, no change was observed in CaMKIIα activation but CREB activation was increased by both low- and high- frequency rTMS. These results have shown the molecular level modulation of rTMS at down-stream level and approaching lymphocyte as a putative source to study brain contexture in the peripheral system with rTMS application. [Copyright &y& Elsevier]

Our aim was to evaluate the effects of a brief PAS on the corticospinal excitability on M1, observing the modulation of the MEP amplitude, the EEG-power and the ERpow, and their correlations, as expression of cortical synaptic strengthening/weakening. We tested on 12 healthy subjects the effect of three PAS conditioning protocols (25ms, 15ms and sham ISI) on the MEP amplitude, the EEG-power, and the ERpow, and their specific correlations, 30’ after the end of the protocols. We found after PAS25ms: MEP amplitude increase; global reduction in α/β-EEGpower and increase in θ/δ; and reduction in ERpow α/β-synchronization; both phenomena were correlated with MEP increase. After PAS15ms: MEP amplitude decrease; global increase in α/β-EEGpower and reduction in θ/δ; and persistent ERpow α/β-synchronization; both phenomena were correlated with MEP amplitude decrease. Looking at these modulations and correlations, it’s conceivable that the effects of PAS25ms could be expression of cortical synaptic potentiation. On the contrary the effects of PAS15ms could mean cortical reset. The modulation could be dependent from cortical GABAergic, glutamatergic and cholinergic circuitries. Beyond the purely neurophysiological aspects, our protocol could be interesting in neuro-rehabilitation, taking account of the effective, quick and persistent modulation of cortical oscillatory activity at bi-hemispheric level. [Copyright &y& Elsevier]

The resection of tumors within or close to eloquent motor areas is usually guided by the compromise between the maximal allowed resection and preservation of neurological functions. Navigated transcranial magnetic stimulation (nTMS) is an emerging technology that can be used for preoperative mapping of the motor cortex. In the present study we report the experience gained during the first year of systematic use of nTMS. We performed pre-surgical mapping by using nTMS in 17 patients with lesions in or close to the precentral gyrus. The study was conducted on consecutive patients scheduled for surgical treatment. Preoperative mapping was performed with the eXimia navigated brain stimulation system. nTMS allowed to exactly localize the motor cortex in 88.2% of cases. In 70.6% it provided the surgeon with new unexpected information about functional anatomy of the motor area, influencing the pre-operative planning. Moreover, in 29.4% these functional information had a clear impact on surgery, making necessary a change of surgical strategy to avoid damage to the motor cortex. nTMS has a large benefit in the treatment of rolandic brain tumors. It adds important information about spatial relationship between functional motor cortex and the tumor and reduces surgical-related post-operative motor deficits. [Copyright &y& Elsevier]

Introduction: In a previous paper we showed that sub-motor threshold 5Hz rENS of the right median nerve when synchronized with sub-motor threshold 5Hz rTMS of the left M1 at a constant interval of 25ms for 2min caused a somatotopically specific increase in cortical excitability (5Hz PASLTP). Objective: In this study we used a similar protocol with a different interstimulus interval (ISI) to evaluate if an asynchronous paired stimulation could cause a somatotopically specific reduction of motor cortical excitability (5Hz PASLTD). We also study the effect of 5Hz PASLTD on intracortical paired-pulse excitability and sensorimotor intracortical inhibition. Material and methods: 5Hz rPAS consisted of 600 pairs of stimuli which were continuously delivered to the left M1 at a rate of 5Hz for 2min in 20 healthy volunteers. Each pair of stimuli consisted of an electrical conditioning stimulus given to the right median nerve followed by a biphasic transcranial magnetic stimulus given to the left M1 controlling APB at 15ms interval. Before and after rPAS (T0–T30–T60), we measured the amplitude of MEP, intracortical inhibition (ICI) and facilitation (ICF), short (SAI 20) and long latency (LAI 200ms) afferent inhibition. We also recorded the MEP amplitudes at rest from first dorsal interosseus (FDI) and extensor carpi radialis (ECR) muscle at baseline and up to 1h after 5Hz rPAS 15ms conditioning. Results: The 5Hz PASLTD protocol caused a significant and somatotopically specific decrease in mean MEP amplitudes in the APB muscle that lasted for at least 1h which was paralleled by a reduction of SAI. Conclusions: These findings show that 2min of 5Hz rPAS at 15ms can induce a long-lasting and somatotopically specific reduction in the excitability of the corticospinal output from the stimulated M1 for 60min. [Copyright &y& Elsevier]

Objective: To explore if sensory information is processed and integrated during sensory-motor plasticity phenomena by using lateral inhibition mechanisms in normal humans and in patients with dystonia. Background: Several evidence suggest that lateral inhibition is a system within sensory-motor cortex operating during the acquisition of new motor tasks in order to select the appropriate muscle sequence to be stored within the final motor engram. This mechanism is thought to be lost in dystonia and this should explain the development of redundant motor memories which could culminate in overflow phenomena and overt dystonia. Methods: We have used transcranial magnetic stimulation to explore lateral inhibition during sensory-motor plasticity in 12 dystonic patients (7 focal hand dystonia, 5 cranial dystonia) and in 8 healthy subjects. In particular we looked at motor evoked potential (MEP) facilitation, in the abductor pollicis brevis (APB) and abductor digiti minimi (ADM), obtained after 5Hz repetitive paired associative stimulation after median (PAS M), ulnar nerve stimulation (PAS U) and median+ulnar nerve (PAS MU) stimulation. In this way we evaluated the ratio MU/M+Ux100 (lateral inhibition index). Moreover, we evaluated the lateral inhibition index (Li index). This parameter is easily obtained by using the following formula: ratio MU/(M+U) x 100. MU is the MEP facilitation measured after PAS with simultaneous stimulation of median and ulnar and M+U is the amount of MEP facilitation, after PAS, induced from stimulation of the individual nerves. Results: Our data confirmed that patients with dystonia had two main abnormalities: first the amount of facilitation was larger than normal subjects; second and more important the spatial specificity was lost. A three-factorial ANOVA demonstrated a significant time×group×conditioning interaction (F =7.9; p =0.005). Lateral inhibition index was similar (about 50%) in healthy subjects and dystonic patients. Conclusions: These data suggest that lateral inhibition is normal in dystonia during sensory-motor plasticity. Another mechanism could contribute to the formation of motor memories with redundant information, which could culminate in overt dystonia. [ABSTRACT FROM AUTHOR]

Sensory loss and ulcero-mutilating features have been observed in hereditary sensory neuropathy type I and in her- editary motor and sensory neuropathy type IIB, also referred as Charcot-Marie-Tooth disease type 2B. To date two loci associated with ulcero-mutilating, neuropathy have been described: CMT2B at 3q13-q22 and HSN I at 9q22.1-q22.3. We performed linkage analysis with chromosomal markers representing the hereditary sensory neuropathy type I and Charcot-Marie-Tooth disease type 213 loci on an Italian family with a severe distal sensory loss leading to an ulcero-mutilating peripheral neuropathy. Negative likelihood-of-odds scores excluded any evidence of linkage to both chromosome 3q13 and chromosome 9q22 markers, confirming the genetic heterogeneity of this clinical entity and the presence of a third locus responsible for ulcero-mutilating neuropathies. [ABSTRACT FROM AUTHOR]