Background
Italy is a high-risk area for multiple sclerosis with 110,000 prevalent cases estimated at January 2016 and 3400 annual incident cases. To study multiple sclerosis epidemiology, it is ...preferable to use population-based studies, e.g., with a registry. A valid alternative to obtain data on entire population is from administrative sources.
Objective
To estimate the incidence of multiple sclerosis in Tuscany using a case-finding algorithm based on administrative data.
Methods
In a previous study, we calculated the prevalence in Tuscany using a validated case-finding algorithm based on administrative data. Incident cases were identified as a subset of prevalent cases among those patients not traced in the years before the analysis period, and the date of the first multiple sclerosis-related claim was considered the incidence date of multiple sclerosis diagnosis. We examined the period 2011–2015.
Results
We identified 1147 incident cases with annual rates ranged from 5.60 per 100,000 in 2011 to 6.58 in 2015.
Conclusions
We found a high incidence rate, similarly to other Italian areas, especially in women, that may explain the increasing prevalence in Tuscany. To confirm this data and to calculate the possible bias caused by our inclusion method, we will validate our algorithm for incident cases.
A neural system matching action observation and execution seems to operate in the human brain, but its possible role in processing sensory inputs reaching the cortex during movement observation is ...unknown.
We investigated somatosensory evoked potentials (SEPs), somatosensory evoked fields (SEFs) and the temporal spectral evolution of the brain rhythms (approximately 10 and approximately 20 Hz) following electrical stimulation of the right median nerve in 15 healthy subjects, during the following randomly intermingled conditions: a pure cognitive/attentive task (mental calculation); the observation of a motoric act (repetitive grasping) with low cognitive content ('Obs-grasp'); and the observation of a complex motoric act (finger movement sequence), that the subject had to recognize later on, therefore reflecting an adjunctive cognitive task ('Obs-seq'). These conditions were compared with an absence of tasks ('Relax') and actual motor performance.
The post-stimulus rebound of the approximately 20 Hz beta magnetoencephalographic rhythm was reduced during movement observation, in spite of little changes in the approximately 10 Hz rhythm. Novel findings were: selective amplitude increase of the pre-central N(30) SEP component during both 'Obs-grasp' and 'Obs-seq', as opposed to the 'gating effect' (i.e. amplitude decrease of the N(30)) occurring during movement execution. The strength increase of the 30 ms SEF cortical source significantly correlated with the decrease of the approximately 20 Hz post-stimulus rebound, suggesting a similar pre-central origin.
Changes took place regardless of either the complexity or the cognitive content of the observed movement, being related exclusively with the motoric content of the action. It is hypothesized that the frontal 'mirror neurons' system, known to directly facilitate motor output during observation of actions, may also modulate those somatosensory inputs which are directed to pre-central areas. These changes are evident even in the very first phases (i.e. few tens of milliseconds) of the sensory processing.
Abstract
Background
Multiple sclerosis (MS) patients are more susceptible to infections than the general population due to the utilization of immunosuppressive drugs (DMDs) which require particular ...attention to the occurrence of infectious events. So, immunisation policies are mandatory or recommended.
Methods
In this pilot study, subjects receiving a diagnosis of relapsing-remitting MS since 2011 at a MS center in central Italy were enrolled. The immunization status against major infectious agents and safety of most used vaccines were recorded.
Results
103 patients (67% females), mean age 42 years, with no or mild disability (85%) were examined. The majority received vaccines against poliomyelitis (92%), hepatitis B (47%), tetanus and diphtheria (89%), but a small percentage got boosters every 10 years (31% for tetanus and 28% for diphtheria); other vaccines evaluated: pertussis (37%), mumps (23%), meningococcus B, C (5%), flu (1%). Evaluating immunization status due to vaccines or illnesses, a significant percentage of patients using immunosuppressive drugs was susceptible to infections, such as measles (44%), chicken pox (32%) and rubella (65%). Only 17% of patients were vaccinated after diagnosis and, regarding vaccine safety, only 1 had a relapse within 6 months following measles, mumps and rubella vaccine.
Conclusions
This study shows a very low number of vaccinations among patients, confirming the need of preventive information on their importance and safety for MS patients: major adverse events of therapy in MS include severe infections and the majority of patients are female in reproductive age. This pilot phase was followed by an ongoing study involving 25 Italian MS Centers and 3000 patients that will provide in 2022 useful results on vaccination policies and safety. The knowledge of immunisation status is crucial for the clinical practice in the management of DMDs, and for the public health policies for a vaccine campaign targeted to MS patients.
Key messages
Lack of information on vaccine safety bring to a low adherence to immunization program. The immunization status of patients is essential for a correct management of therapies.
Both dopamine agonists and levodopa may induce episodes termed "sleep attacks" in patients with PD. These episodes are well detailed behaviorally, but little is known about their neurophysiologic ...characterization. The authors performed a 24-hour polysomnography (PSG) in a PD patient taking pergolide in combination with levodopa, in which four of these diurnal sleep episodes occurred. PSG findings were followed up after pergolide withdrawal. Sleep episodes shared with narcolepsy both behavioral and EEG findings. However, pergolide partly restored a more physiologic sleep architecture, which was disrupted during therapy with levodopa alone.
In this paper, we used repetitive transcranial magnetic stimulation (rTMS) in 18 normal subjects to investigate whether the ventral posterior parietal cortex (PPC) plays a causal role on visuospatial ...attention and primary consciousness and whether these 2 functions are linearly correlated with each other. Two distinct experimental conditions involved a similar visual stimuli recognition paradigm. In “Consciousness” experiment, number of consciously perceived visual stimuli was lower by about 10% after rTMS (300 ms, 20 Hz, motor threshold intensity) on left or right PPC than after sham (pseudo) rTMS. In “Attentional” Posner's experiment, these stimuli were always consciously perceived. Compared with sham condition, parietal rTMS slowed of about 25 ms reaction time to go stimuli, thus disclosing effects on endogenous covert spatial attention. No linear correlation was observed between the rTMS-induced impairment on attention and conscious perception. Results suggest that PPC plays a slight but significant causal role in both visuospatial attention and primary consciousness. Furthermore, these high-level cognitive functions, as modulated by parietal rTMS, do not seem to share either linear or simple relationships.
Objective: To investigate the after-effects of 0.3 Hz repetitive transcranial magnetic stimulation (rTMS) on excitatory and inhibitory mechanisms at the primary motor cortex level, as tested by ...single-pulse TMS variables.
Methods: In 9 healthy subjects, we studied a wide set of neurophysiological and behavioral variables from the first dorsal interosseous before (Baseline), immediately after (Post 1), and 90 min after (Post 2) the end of a 30 min long train of 0.3 Hz rTMS delivered at an intensity of 115% resting motor threshold (RMT). Variables under investigation were: maximal M wave, F wave, and peripheral silent period after ulnar nerve stimulation; RMT, amplitude and stimulus–response curve of the motor evoked potential (MEP), and cortical silent period (CSP) following TMS; finger-tapping speed.
Results: The CSP was consistently lengthened at both Post 1 and Post 2 compared with Baseline. The other variables did not change significantly.
Conclusions: These findings suggest that suprathreshold 0.3 Hz rTMS produces a relatively long-lasting enhancement of the inhibitory mechanisms responsible for the CSP. These effects differ from those, previously reported, of 0.9–1 Hz rTMS, which reduces the excitability of the circuits underlying the MEP and does not affect the CSP. This provides rationale for sham-controlled trials aiming to assess the therapeutic potential of 0.3 Hz rTMS in epilepsy.
Introduction– Primary intraventricular haemorrhage (PIVH) is an uncommon type of intracerebral haemorrhage. Relatively little is known about clinical and imaging features, and even less about ...prognosis and predictors of mortality. Material and methods– We analysed clinical and imaging features, causative factors and outcome of 26 patients with CT brain scan evidence of PIVH. A multivariate regression model of failure time data was used to assess predictors of in‐hospital mortality. Results– Loss of consciousness was the first manifestation of PIVH in six patients and occurred after all other symptoms in five. In other patients, onset was characterized by headache, vomiting, confusion and disorientation (n=8) or by headache with or without vomiting (n=7). Angiography revealed vascular malformations in eight patients (31%). Other possible causative factors were clotting disorder in one patient and arterial hypertension in 10. No cause was identified in seven patients. Early hydrocephalus was the most frequent complication and resolved spontaneously in a minority of patients. In‐hospital mortality was high (42%): four patients died early of direct consequence of bleeding and seven died after clinical worsening because of increasing hydrocephalus or other adverse events. Multivariate analysis indicated Glasgow Coma Scale ≤ 8 (OR 4.67; 95% CI 1.22–17.92) and early hydrocephalus (OR 4.93; 95% CI 1.13–21.59) as independent predictors of in‐hospital mortality. Conclusion– In patients with PIVH, hydrocephalus seems to be a critical determinant of in‐hospital mortality and this suggests the need for early treatment strategies.
Increased plasma concentrations of total homocysteine (tHcy; mild-moderate hyperhomocysteinemia: 15-50 μ
tHcy) are considered an independent risk factor for the onset/progression of various diseases, ...but it is not known about how the increase in tHcy causes pathological conditions.
Reduced homocysteine (HSH ∼1% of tHcy) is presumed to be toxic, unlike homocystine (∼9%) and mixed disulfide between homocysteine and albumin (HSS-ALB; homocysteine Hcy-albumin mixed disulfide, ∼90%). This and other notions make it difficult to explain the pathogenicity of Hcy because: (i) lowering tHcy does not improve pathological outcomes; (ii) damage due to HSH usually emerges at supraphysiological doses; and (iii) it is not known why tiny increments in plasma concentrations of HSH can be pathological.
Albumin may have a role in Hcy toxicity, because HSS-ALB could release toxic HSH
thiol-disulfide (SH/SS) exchange reactions in cells. Similarly, thiol-disulfide exchange processes of reduced albumin (albumin with free SH group of Cys34 HS-ALB) or
-homocysteinylated albumin are plausible alternatives for initiating Hcy pathological events. Adverse effects of albumin and other data reviewed here suggest the hypothesis of a role of albumin in Hcy toxicity.
HSS-ALB might be involved in disruption of the antioxidant/oxidant balance in critical tissues (brain, liver, kidney). Since homocysteine-albumin mixed disulfide is a possible intermediate of thiol-disulfide exchange reactions, we suggest that homocysteinylated albumin could be a new pathological factor, and that studies on the redox role of albumin and mixed disulfide production
thiol-disulfide exchange reactions could offer new therapeutic insights for reducing Hcy toxicity.
To determine whether diabetes and admission hyperglycemia in nondiabetic patients influence outcome and the occurrence of cerebral and medical complications after intracerebral hemorrhage (ICH).
The ...study sample included 764 patients with ICH. The effects of diabetes and admission hyperglycemia were examined in relation to 30-day and 3-month mortality using Cox regression models controlling for potential confounders. The analysis was conducted for the entire sample of patients and repeated in comatose and noncomatose patients.
Among comatose patients, neither diabetes nor admission hyperglycemia contributed significant predictive information, as nearly all patients died. In noncomatose patients, diabetes was an independent predictor of 30-day (odds ratio OR 1.31; 95% CI 1.08 to 1.58) and 3-month (OR 1.30; 95% CI 1.08 to 1.56) mortality and was associated with a greater incidence of infectious (OR 1.24; 95% CI 1.03 to 1.49) and cerebral (OR 1.42; 95% CI 1.10 to 1.83) complications. Among nondiabetic patients with Glasgow Coma Scale score of >8, hyperglycemia was an independent predictor of 30-day (OR 1.29; 95% CI 1.05 to 1.58) and 3-month (OR 1.27; 95% CI 1.05 to 1.53) mortality and was associated with a greater incidence of cerebral complications (OR 1.47; 95% CI 1.12 to 2.94).
Both diabetes and admission hyperglycemia in nondiabetic patients are predictors of poor outcome after supratentorial ICH. This may be related to the greater incidence of cerebral and infectious complications in diabetic patients and of cerebral complications in hyperglycemic nondiabetic patients.
Several lines of evidence suggest that low-rate repetitive transcranial magnetic stimulation (rTMS) of the motor cortex at 1 Hz reduces the excitability of the motor cortex and produces metabolic ...changes under and at a distance from the stimulated side. Therefore, it has been suggested that rTMS may have beneficial effects on motor performance in patients with movement disorders. However, it is still unknown in what way these effects can be produced. The aim of the present study is to investigate whether rTMS of the motor cortex (15 min at 1 Hz) is able to modify the voluntary movement related cortical activity, as reflected in the Beretischaftspotential (BP), and if these changes are functionally relevant for the final motor performance. The cortical movement-related activity in a typical BP paradigm of five healthy volunteers has been recorded using 61 scalp electrodes, while subjects performed self-paced right thumb oppositions every 8-20 s. After a basal recording, the BP was recorded in three different conditions, counterbalanced across subjects: after rTMS stimulation of the left primary motor area (M1) (15 min, 1 Hz, 10% above motor threshold), after 15 min of sham rTMS stimulation and following 15 min of voluntary movements performed with spatio-temporal characteristics similar to those induced by TMS. The tapping test was used to assess motor performance before and after each condition. Only movement-related trials with similar electromyographic (onset from muscular 'silence') and accelerometric patterns (same initial direction and similar amplitudes) were selected for computing BP waveforms. TMS- evoked and self-paced thumb movements had the same directional accelerometric pattern but different amplitudes. In all subjects, the real rTMS, but neither sham stimulation nor prolonged voluntary movements, produced a significant amplitude decrement of the negative slope of the BP; there was also a shortening of the BP onset time in four subjects. The effect was topographically restricted to cortical areas which were active in the basal condition, irrespective of the basal degree of activation at every single electrode. No changes in the tapping test occurred. These findings suggest that rTMS of the motor cortex at 1 Hz may interfere with the movement related brain activity, probably through influence on cortical inhibitory networks.