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Purpose: Status epilepticus (SE) is associated with high morbidity and mortality. This multicenter retrospective cohort study aims to identify the factors associated with the occurrence of SE and the predictors of its recurrence in patients with adult-onset seizures., Methods: We retrospectively analyzed data of 1115 patients with seizure onset>18 years, observed from 1983 to 2020 in 7 Italian Centers (median follow-up 2.1 years). Data were collected from the databases of the Centers. Patients with SE were consecutively recruited, and patients without SE history were randomly selected in a 2:1 ratio. To assess determinants of SE, different clinical-demographic variables were evaluated and included in univariate and multivariate logistic regression model., Results: Three hundred forty-seven patients had a SE history, whereas the remaining 768 patients had either isolated seizures or epilepsy without SE history. The occurrence of SE was independently associated with increasing age at onset of disease (OR 1.02, 95% CI 1.01--1.03, p<0.001), female sex (OR 1.39, 95% CI 1.05--1.83, p=0.02) and known etiology (OR 3.58, 95% CI 2.61--4.93, p<0.001). SE recurred in 21% of patients with adult-onset SE and recurrence was associated with increasing number of anti-seizure medications taken at last follow-up (OR 1.88, 95% CI 1.31--2.71, p<0.001)., Conclusions: In patients with adult-onset seizures, SE occurrence is associated with known etiologies, advanced age and female sex. Patients with recurrent SE are likely to have a refractory epilepsy, deserving careful treatment to prevent potentially fatal events., (Copyright © 2021 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Objectives: Altered cortical visuomotor integration has been involved in the pathophysiology of freezing of gait (FoG) in parkinsonism. The aim of this study was to assess the connections between the primary visual (V1) and motor (M1) areas with a paired-pulse, twin-coil transcranial magnetic stimulation (TMS) technique in patients with FoG., Methods: Twelve Parkinson's disease (PD) patients suffering from levodopa-responsive-FoG (off-FoG) were compared with 12 PD patients without FoG and 12 healthy subjects of similar age/sex. In the "off" condition, visuomotor connections (VMCs) were assessed bilaterally. A conditioning stimulus over the V1 phosphene hotspot was followed at interstimulus intervals (ISIs) of 18 and 40ms by a test stimulus over M1, to elicit motor evoked potentials (MEPs) in the contralateral first dorsal interosseous muscle., Results: Significant (P<0.01), bilateral effects due to VMCs were detected in all three groups, consisting of a MEP suppression at ISI 18 and 40ms. However, in PD patients with FoG, the MEP suppression was significantly (P<0.05) enhanced, both at ISI 18-40ms, in comparison with the other two groups. The phenomenon was limited to the right hemisphere., Conclusions: PD patients with FoG showed an excessive inhibitory response of the right M1 to inputs travelling from V1 at given ISIs. Right-sided alterations of the cortical visuomotor integration may contribute to the pathophysiology of FoG., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Limb-girdle myasthenia gravis (LGM) is an uncommon clinical picture related to an antibody-mediated blockage of the neuromuscular junction. We describe a 44-year old man who presented with a proximal limbs' weakness that resembled a myopathic disorder. The repetitive nerve stimulation at 3Hz showing a decremental response suggested myasthenia, that was confirmed by the presence of an increased titer of anti-acetylcholine receptor antibodies (AChRAbs), and of hyperplastic foci at thymus histology. Symptomatic treatment with pyridostigmine was not effective, whereas the patient improved adding Azathioprine. In conclusion, a myopathic-like clinical picture in an adult could be caused by LMG. Thymus pathology, or (rarely) increased AChRAbs could support the diagnosis of LGM., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: The pathophysiology of migraine with or without aura (MA, MO) is still a matter of debate. We thus studied patients with MA and MO by means of paired-pulse flash-visual evoked potentials (paired F-VEPs). This technique, recently revived, analyses the overall excitability of visual system as detected from the cortical occipital signal., Methods: We enrolled 13 adult patients with MO and 13 with MA. Twenty-two normal subjects of similar age and sex acted as controls. Stimuli were single flashes, intermingled at random to flash pairs at critical interstimulus intervals (ISIs, 16.5-125ms) with closed and open eyes. The "single"(unconditioned) F-VEP was split into a "main complex" (50-200ms after the flash) and a "late response" (200-400ms). As for paired stimulation, the "test" F-VEP emerged from electronic subtraction of the "single" F-VEP to the "paired" F-VEP. Its size was expressed as "test"/"single"F-VEP∗100., Results: As for paired F-VEPs, the "main complex" of the "test" F-VEP in the MA group did not show the size reduction (at ISIs 50-62.5ms) which was typical among the control and MO groups (p⩽0.016) in the "eyes-closed" state., Conclusions: Paired F-VEPs document a defective neural inhibition in the visual system of patients with MA., Significance: Paired F-VEPs may warrant inclusion in future preclinical/clinical studies, to evaluate its potential role in the pathophysiology and management of MA., (Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Purpose: Abnormal cortical plasticity has been hypothesized to play a crucial role in the pathogenesis of juvenile myoclonic epilepsy (JME). To study the motor cortical plasticity we used paired associative stimulation (PAS). When a repetitive electrical stimulus to the median nerve is paired with a transcranial magnetic stimulus (TMS) pulse over the controlateral motor cortex with at an interstimulus interval (ISI) of 21.5-25ms, a long term potentiation (LTP)-like synaptic plasticity is induced in the corticospinal system. Aim of this study was to investigate the motor cortex LTP-like synaptic plasticity by means of PAS in patients with JME., Methods: Twelve adult patients with JME were compared with 13 healthy subjects of similar age and sex. PAS consisted of 180 electrical stimuli of the right median nerve paired with a single TMS over the hotspot of right abductor pollicis brevis (APB) at an ISI of 25ms (PAS25). We measured motor evoked potentials (MEPs) before and after each intervention for up to 30min., Results: In healthy subjects the PAS25 protocol was followed by a significant increase of the MEP amplitude (p<0.001). On the contrary, in patients with JME, the MEP amplitude did not change., Conclusion: Defective motor cortex plasticity is likely involved in the pathogenesis of JME., (Copyright © 2015 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Purpose: In vitro or in animal models of epilepsy, ghrelin showed a clear anticonvulsant action, whose mechanisms are somewhat obscure. In humans however, a controversial relation exists between ghrelin and epilepsy. Yet most studies investigated just total ghrelin levels, without a proper distinction between acylated (AG) or unacylated ghrelin (UAG). We thus evaluated separately AG and UAG interictal levels in adult patients with epilepsy, and their relation to clinical features., Method: Cross-sectional study in a tertiary referral centre. Fifty-six patients were recruited: 19 with idiopathic generalized epilepsy, 18 with cryptogenic focal epilepsy and 19 with symptomatic focal epilepsy. Twenty-six healthy subjects of similar age, sex and body mass index (BMI) acted as controls. AG and UAG levels were measured following an overnight fasting and contrasted to the clinical and biometric features., Results: AG and UAG levels were similar between patients and controls. The AG/UAG ratio was higher in patients, also when weighted for covariates (age, BMI, gender, and drugs). Splitting patients according to their epileptic syndrome, drug-resistance or antiepileptic drug number/type resulted in no significant difference in AG, UAG or their ratio. Yet, AG and UAG levels were positively predicted by disease duration, independently by confounders., Conclusion: In adult patients with epilepsy, interictal ghrelin levels did not differ from controls, though the AG/UAG ratio was imbalanced. Interpretation of the latter phenomenon is uncertain. Further, levels of AG and UAG were in direct proportion to disease duration, which may represent a long-term compensatory mechanism, antagonistic to the epileptic process., (Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Objective: We aimed at reviving with modern technology the paired flash-visual evoked potential (F-VEP) testing of the visual system excitability. In the 1960s, methodological problems hindered this test, which was expected to provide important physiologic information., Methods: We studied 22 consenting healthy subjects (10 men). We recorded F-VEPs from electrodes over occipital and central brain regions. We delivered single flashes, mixed at random to flash pairs at the interstimulus interval (ISI) of 333, 125, 62.5, 50, 33, and 16.5 ms, (i.e. an internal frequency (IF) of 3, 8, 16, 20, 30, and 60 Hz). Recordings were performed with the subject's eyes closed and opened. The F-VEP was split into a "main complex" and an "afterdischarge", which we analyzed statistically in relation to the eye state (closed or open) and to the changes due to paired stimulation., Results: The eye state affected the single F-VEP size, latency and shape significantly (p<0.05). On paired stimulation, the test (second) F-VEP exhibited significant (p<0.05), ISI-dependent size changes, such as a progressive decrease for ISIs from 62.5 to 16.5 ms (IFs of 16-60 Hz), whose timing/amount varied significantly (p<0.05) according to the eye state and to the F-VEP epoch considered. Suppression of the test F-VEP was never complete, even for the shortest ISI (ISI=16.5 ms, IF=60 Hz)., Conclusions: The eye state (closed or open) must be considered meticulously when studying F-VEPs. F-VEP changes on paired stimulation express neural inhibition within the visual system, which can be depicted as ISI-dependent curves., Significance: Modern equipment and simplified measures render this an easy test, with statistical validity, providing specific information on the excitability properties of the visual system., (Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Objective: Motor cortex excitability can be measured by transcranial magnetic stimulation (TMS) using different coil types, but paired-TMS was originally devised with a figure-of-eight coil. We asked whether the most popular, circular coil was suited to the every-day assessment of cortical excitability, particularly paired-TMS indexes, and if it reduced the measurement error., Methods: We studied 12 right-handed, healthy subjects (34±7.6 years). Resting motor threshold (MT), cortical silent period (CSP), short-interval intracortical inhibition (SICI) at the 2, 3, 4 and 5 ms interstimulus intervals (ISIs) and intracortical facilitation (ICF) at the 14 and 16 ms ISIs were measured. Intrinsic variability of these indexes was evaluated in terms of Coefficients of Variation, to estimate the measurement error. This sequence was carried out both using a figure-of-eight coil over the hand motor area and a circular coil centred at the vertex. Testing was repeated 8-13 months later., Results: On average, MT, SICI and ICF did not show any statistically significant difference (p>0.05) when studied with the figure-of-eight as compared with the circular coil. CSP was significantly shorter (p=0.007) with the figure-of-eight coil. Using either coil did not affect measurement variability. There was no significant session-to-session group difference at any of the variables using either coil type., Conclusions: Except for the CSP duration, the TMS testing and retesting of cortical excitability, particularly the paired-pulse indexes, did not vary significantly as a function of the coil used., Significance: Routine circular coils can be used reliably in paired-TMS studies designed to measure longitudinal changes in cortical excitability though they do not reduce the measurement error., (Copyright © 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by recurrent thrombotic events and/or pregnancy morbidity that may be isolated (Primary APS) or associated with other diseases, mainly of autoimmune origin (Secondary APS). A variety of neurological symptoms may occur in association with the disease, including movement disorders. We report on a 79 year old woman with an unremarkable past medical history who progressively developed psychomotor agitation and insomnia through a period of four months, followed by an acute onset complex hyperkinetic syndrome with chorea, focal left foot dystonia, oral dyskinesias and severe speech impairment. Brain MRI showed multiple subcortical lesions without basal ganglia involvement, and a large cortical lesion in the left posterior temporal lobe that appeared to be ischemic. These findings along with a strongly elevated titer of anticardiolipin (aCL) and anti-beta(2) glycoprotein-I antibodies and positive Lupus Anticoagulant (LAC) suggested a diagnosis of Antiphospholipid Syndrome, confirmed 14 weeks later as a Primary syndrome. The autoimmune mechanisms possibly responsible for the patient's clinical picture are discussed. This case underlines the importance of taking into account APS as a cause of unusual movement disorders even in elderly patients without evidence of previous thrombotic events.

Objectives: Disease manifestations such as photic cortical reflex myoclonus or myoclonus due to intermittent light stimulation rely on a pathologic interaction between non-structured visual inputs and the corticospinal system. We wanted to assess the normal interaction, if any, between a prior photic input and the output of the cortico-motoneuron connection., Methods: In 9 consenting healthy subjects we quantified the changes exerted by a sudden, unexpected bright light flash on (i) the motor potentials (MEPs) evoked in the right first dorsal interosseous muscle (FDI) by transcranial magnetic or electrical stimulation (TMS/TES) of the primary motor cortex, (ii) the FDI F-waves and (iii) the soleus H-wave. Separately, we measured the simple reaction times to the flash itself. All determinations were repeated twice with an interval of 2-24 months., Results: When the flash preceded TMS by 55-70 ms, the MEP size was reduced, while at interstimulus intervals (ISIs) of 90-130 ms it was enlarged. Statistical significance (P<0.05) emerged at ISIs of 55, 70, 100, 105 and 120 ms. Conversely, the MEP latency was prolonged at ISIs of 55-70 ms and shortened at ISIs of 90-130 ms (P<0.05 at ISIs of 55, 110 and 130 ms). Electrical MEPs were enhanced at an ISI of 120 ms. The F-wave size showed a non-significant trend of enhancement at ISIs of 90-130 ms. The soleus H-wave showed significant enlargement at ISIs of 90-130 ms (P<0.05 at ISIs of 100 and 105 ms). The minimum reaction time was on average 120 ms., Conclusions: An unexpected photic input, to which no reaction is planned, can cause an early inhibition of the responses to TMS. We think its origin lies within the primary motor cortex, since it is not associated with changes in spinal excitability or electrical MEPs. A later facilitation persists using TES and has a temporal relationship with an enlargement of the soleus H-wave. Thus, it likely results from activation of descending (possibly reticulospinal) fibers that excite the spinal motor nucleus.

Objective: To evaluate possible functional asymmetries of the motor cortex on the hand-dominant versus the non-dominant hemisphere., Methods: We assessed the handedness of 15 consenting volunteers using the Edinburgh Inventory. They were divided in two groups: 9 right-handers and 6 left-handers. We used single- and paired-transcranial magnetic stimulation (TMS) to measure the relaxed and active motor threshold and the ipsilateral cortico-cortical inhibition and facilitation curve for both hand motor areas. We looked for hemispheric asymmetries of variables related to the side of stimulation (dominant versus non-dominant) and to handedness., Results: We found no significant intra- or intergroup hemispheric asymmetry for the relaxed and active thresholds. Among the right-handers, the cortico-cortical inhibition and facilitation curve showed an increased amount of facilitation in the dominant as compared with the non-dominant hand area. No such changes were seen among the left-handers. Both the dominant and the non-dominant hand areas of the right-handers showed more inhibition and less facilitation on the cortico-cortical inhibition and facilitation curve than the corresponding areas of left-handers., Conclusion: In the right-handers, paired TMS studies showed a functional asymmetry of the motor cortex between the dominant and the non-dominant hand. The left-handers did not show this lateralization. Under TMS investigation their motor cortex function appeared different from that of right-handers.