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Background: Italy was one of the first affected countries by coronavirus disease 2019 (COVID-19) pandemic. Public health measures like quarantine or national lockdown were adopted, with negative psychological and clinical effects on patients with chronic diseases. To investigate the impact of lockdown on patients with multiple sclerosis (MS), we developed a 36 items self-report questionnaire. Methods: Questionnaires were emailed to 120 patients with MS and 100 with chronic migraine (CM) as a control group, matched for age, sex, and education. The questionnaire was divided into five domains, evaluating concerns about 1) MS and therapy during COVID-19 pandemic, 2) personal and family caregiving, 3) working activities, 4) general and disease-related emotions during the lockdown, 5) future expectations concerning health status, social life, and working activity. Results: patients with MS had higher scores than those with CM in domains 4 and 5, investigating respectively general and disease-related emotions and future expectations (p= 0.05 and 0.02 respectively). About half of the patients with MS expressed some concern about the need to continue their therapy during the pandemic compared to people with CM (p= 0.0002). Conclusions: Covid-19 pandemic had a more negative impact on psychological status of patients with MS compared with those with CM

Background The disease-modifying therapies (DMTs) largely used in multiple sclerosis (MS) may result in higher infectious risk. Objective We aimed to investigate the infectious risk in DMT-treated MS patients. Methods MS patients were evaluated for infectious risk before starting, switching or during DMT. Results In this three-year observational cohort study 174 MS patients were enrolled. Among them, 18 patients were anti-HBc + and 19 patients were QuantiFERON®-TB Gold In-Tube (QFT) + . No patients with anti-HBc + showed a detectable HBV-DNA and all started DMT. Among QTB + patients, 17 latent TB infections (LTBIs) and 2 active TB infections (TBIs) were identified. After one month of LTBI prophylaxis or TB treatment, respectively, all patients started DMTs. Overall, 149 started DMTs. During DMTs, one ocrelizumab-treated patient with anti-HBc + developed HBV reactivation and six patients (3 on natalizumab, 2 on ocrelizumab and 1 on IFN-β) showed reactivation of HSV-1, with detectable plasma DNA. Finally, 1 cladribine-treated patient experienced VZV reactivation. All the reactivations of latent infections have been successfully treated. Conclusion Screening of infectious diseases in DMT candidate MS patients helps to mitigate the infectious risk. During DMTs, a regular assessment of infectious risk allows to avoid discontinuing MS therapy and guarantees a higher degree of safety.

Background and purpose Stroke-associated pneumonia (SAP) affects 10 to 38% of patients in the acute phase of stroke. Stroke patients diagnosed with dysphagia have an 11-fold higher risk of developing SAP. Thus, identifying dysphagic patients through a highly accurate screening tool might be crucial in reducing the incidence of SAP. We present a case–control study designed to evaluate efficacy in reducing the risk of SAP between two swallowing screening tools, the classic water swallow test (WST) and a recently validated tool such as the GLOBE-3S (the Sapienza GLObal Bedside Evaluation of Swallowing after Stroke), which is a highly sensitive swallowing screening tool particularly accurate in detecting silent aspiration as well. Methods We analyzed the occurrence of dysphagia in 100 acute stroke patients distributed in two groups: half were screened with WST and the other half with GLOBE-3S. Results Dysphagia was diagnosed in 28 patients. The main result is that, among patients who passed the dysphagia screenings, none of those screened with the GLOBE-3S method developed pneumonia compared to 31.82% in the WST group. Discriminant function analysis (DFA) showed that NIH Stroke Scale (NIHSS) score and the dysphagia screening method (i.e., GLOBE-3S vs. WST) were the two main factors in the SAP’s predicting model and the only significant ones per se. Conclusions The new GLOBE-3S screening test can reduce the risk of SAP compared to WST.

Objective To study the effects of trains of repetitive transcranial magnetic stimulation (rTMS) over the motor cortex in patients with chronic migraine (CM) with or without medication overuse (MOH). Subjects and methods Thirty-two patients (CM [n = 16]; MOH [n = 16]) and 16 healthy volunteers (HVs) underwent rTMS recording. Ten trains of 10 stimuli each (120% resting motor threshold) were applied over the left motor cortex at 1 Hz or 5 Hz in random order. The amplitude of motor evoked potential (MEP) was evaluated from electromyographic recording in the first dorsal interosseous muscle. The slope of the linear regression line for the 10 stimuli for each participant was calculated using normalized data. Results rTMS-1 Hz had a normal depressive effect on MEP amplitude in all groups. rTMS-5 Hz depressed instead of potentiating MEP amplitudes in MOH patients, with a significantly different response from that in HVs and CM patients. The slope of the linear regression of MEP amplitudes was negatively correlated with pain intensity in CM patients, and with the duration of overuse headache in MOH patients. Conclusions This different plastic behaviour suggests that MOH and CM, despite exhibiting a similar clinical phenotype, have different neurophysiological learning processes, probably related to different pathophysiological mechanisms of migraine chronification.

O028. Thalamo-cortical network changes during the migraine cycle: insights from MRI-based microstructural and functional resting-state network correlation analysis Gianluca Coppola, Antonio Di Renzo, Emanuele Tinelli, Chiara Lepre, Elisa Iacovelli, Cherubino Di Lorenzo, Giorgio Di Lorenzo, Vincenzo Parisi, Mariano Serrao, Flavia Pauri, Giancarlo Fiermonte, Claudio Colonnese, Jean Schoenen, Francesco Pierelli

Transcranial magnetic stimulation (TMS) of the motor cortex of one hemisphere (conditioning stimulus, CS) inhibits EMG responses evoked in distal hand muscles by a magnetic stimulus given at appropriate interval later over the opposite hemisphere (test stimulus, TS). The common interpretation attributes this effect to an inhibition produced at cortical level via a transcallosal route. The variability of cortical excitability as measured by the interhemispheric paired-pulse (PP) technique has been assessed in healthy subjects in order to compare sub- and supra-threshold intensity of CS (80% versus 120% of individual motor threshold, MT). Within- and between-subject variability relating, respectively, to interhemispheric and gender differences were also assessed. Results point to an efficacy of a magnetic CS on one hemisphere in inhibiting EMG responses of the abductor digiti minimi (ADM) stimulated by a TS delivered over the opposite hemisphere in a range of intervals centered at 12ms. These reductions were produced by the 120% suprathreshold CS, while the 80% subthreshold CS did not affect EMG responses. Females showed a higher transcallosal inhibition than males, suggesting gender differences in interhemispheric connectivity that concern the anterior half of the trunk of the corpus callosum.

Neurophysiological investigations have demonstrated that there are unique fluctuations in the migraine brain functional activity between the ictal and interictal periods. Here we investigated the possibility that there are fluctuations over time also in whole brain morphometry of patients affected by episodic migraine without aura (MO). Twenty-four patients with untreated MO underwent 3T MRI scans during ( n = 10) or between attacks ( n = 14) and were compared to a group of 15 healthy volunteers (HVs). We then performed voxel-based-morphometry (VBM) analysis of structural T1-weighted MRI scans to determine if changes in brain structure were observed over the course of the migraine cycle. Interictally, MO patients had a significantly lower gray matter (GM) density within the right inferior parietal lobule, right temporal inferior gyrus, right superior temporal gyrus, and left temporal pole than did HVs. Ictally, GM density increased within the left temporal pole, bilateral insula, and right lenticular nuclei, but no areas exhibited decreased GM density. These morphometric GM changes between ictal and interictal phases suggest that abnormal structural plasticity may be an important mechanism of migraine pathology. Given the functional neuroanatomy of these areas, our findings suggest that migraine is a condition associated with global dysfunction of multisensory integration and memory processing.

Motor deficits affect patients with Alzheimer's disease only at later stages. Recent studies demonstrate that the primary motor cortex is affected by neuronal degeneration accompanied by the formation of amyloid plaques and neurofibrillary tangles. It is conceivable that neuronal loss is compensated by reorganization of the neural circuitries occurring along the natural course of the disease, thereby maintaining motor performances in daily living. Cortical motor output to upper limbs was tested via motor-evoked potentials from forearm and hand muscles elicited by transcranial magnetic stimulation of motor cortex in 16 patients with mild Alzheimer's disease without motor deficits. Motor cortex excitability was increased, and the center of gravity of motor cortical output, as represented by excitable scalp sites, showed a frontal and medial shift, without correlated changes in the site of maximal excitability (hot-spot). This may indicate functional reorganization, possibly after the neuronal loss in motor areas. Hyperexcitability might be caused by a dysregulation of the intracortical GABAergic inhibitory circuitries and selective alteration of glutamatergic neurotransmission. Such findings suggest that motor cortex hyperexcitability and reorganization allows prolonged preservation of motor function during the clinical course of Alzheimer's disease.

Background Neurophysiological investigations have demonstrated that there are distinctive fluctuations in the brain’ se lectric signals between the ictal and interictal periods of recurrent migraine. Whether structural plasticity of the brain is also an important feature of episodic migraine remains unresolved. Aim We therefore investigated the possibility that there are fluctuations over time in whole brain grey matter morphometry of patients affected by episodic migraine without aura (MO). Method Twenty-four patients with untreated MO underwent MRI scans (3-Tesla Siemens Verio) during (n = 10) or between attacks (n = 14) and were compared to a group of 15 healthy volunteers (HV). We then performed voxelbased-morphometry (VBM) analysis of structural T1-weighted MRI scans to determine if changes in brain structure were observed over the course of the migraine cycle. Results During the interictal phase, MO patients had a significantly lower grey matter (GM) density within the right inferior parietal lobule, right temporal inferior gyrus, right superior temporal gyrus, and left temporal pole than did HV. During attacks, GM density increased within the left temporal pole, bilateral insula, and right lenticular nuclei, but no areas exhibited decreased GM density. Conclusion The morphometric GM changes between ictal and interictal phases reported in the present study suggest that abnormal structural plasticity may be an important mechanism of migraine pathology. Given the functional neuroanatomy of these areas, our findings suggest that migraine is a condition associated with global dysfunction of multisensory integration and memory processing. No conflict of interest.

The most common mononeuropathy in the lower extremity involves the nerve. We retrospectively evaluated the etiological predisposing factors and clinical-neurophysiological features of 36 patients affected by peroneal mononeuropathy (PM). In 30 patients, a clear predisposing factor was identified. PM was more frequently perioperative (11 cases), associated with axonal involvement. Unexpectedly, PM was not only due to surgery close to the peroneal region, but was mostly associated with hip surgery and, rarely, with thoracic-abdominal surgery. A postural predisposing factor of PM was also frequently observed, usually associated with a pure conduction block. Conversely, most patients with bedridden predisposing factor presented axonal involvement, which was rarely associated with conduction block. In 25 of 36 PM cases, a long-term follow-up lead to an improvement (12 cases) or to good recovery (13 cases) of PM. In conclusion, our study shows that: (1) in most PM cases it is possible to identify a predisposing factor; (2) there is a good correlation between predisposing factor and neurophysiological involvement, and (3) PM usually has usually a good prognosis.

We report the clinical, serological, and neurophysiological findings in seven patients with foodborne botulism caused by ingestion of black olives in water. The clinical picture was characterized by mild symptoms with a long latency of onset and by involvement of cranial and upper limb muscles; only one patient, a child, developed respiratory failure. Spores of Clostridium botulinum were found in stools in some but not all cases. Conventional neurophysiological tests had low sensitivity; abnormal findings were present only in the patient with severe clinical involvement, in whom compound muscle action potentials (CMAPs) appeared reduced. Repetitive nerve stimulation at a high rate showed pseudofacilitation and not true posttetanic facilitation, but single-fiber electromyography (SFEMG) showed abnormalities of neuromuscular transmission in every case. Neurophysiological evaluation, particularly SFEMG, is important because it allows rapid identification of abnormal neuromuscular transmission while bioassay studies are in progress.

We report a case of a 53-year-old man with a 2-year history of progressive gait and balance disturbance, supranuclear ophthalmoparesis, mild dysarthria and dysmetria. EMG revealed a lower limb axonal sensory-motor neuropathy, while MR imaging demonstrated a small focal lesion in the right frontal lobe, mild diffuse hyperintensity of the periventricular white matter and diffuse brain atrophy. Magnetic resonance spectroscopy revealed a mild decrease in N-acetyl-aspartate peak and an increase in the choline peak in the small right frontal lesion and within 6 voxels of interest in normal appearing cerebral tissue. According to the clinical picture the diagnosis of WD was made by the positivity of PCR for T. whipplei DNA on CSF. After treatment the patient showed a mild clinical improvement although MR images and laboratory test remained unchanged. The MRS findings suggest that the pathological process of the disease diffusely involves the brain. Despite the absence of gastrointestinal involvement WD should be suspected in all complex and atypical neurological pictures, even in presence of peripheral involvement, in order to be able to start treatment promptly.

Erdheim-Chester disease (ECD) is a rare, non-Langerhans cell histiocytosis of unknown origin characterized by systemic infiltrates of non-Langerhans histiocytes, usually involving multiple organs, including CNS.1–3 Skeletal involvement is considered highly specific and typical radionuclide bone scan findings include bilateral, symmetric increased tracer uptake in the metaphyses and diaphyses of the long bones, mainly femur and tibiae, with epiphyseal sparing.3 Once suspected in the living patient, the diagnosis of ECD needs to be confirmed by surgical biopsy of the affected tissues. Clinical manifestations are protean4 and in cases with neurologic involvement MRI can help diagnosis.5 We report 2 cases of adult-onset ECD with neurologic involvement and strikingly similar brain MRI pattern of abnormalities. ### Case 1. A 65-year-old man was admitted with a 4-year history of progressive loss of coordination and balance. He had had central diabetes insipidus for 3 years. Neurologic examination showed cerebellar ataxia and pyramidal signs. Dysarthria and dysphagia were also present, suggesting possible supranuclear bulbar involvement. Sensory, cognitive functions, and cranial nerves were normal. Biochemical parameters, including serum sodium, potassium, magnesium, and phosphate levels, were normal. A brain MRI showed diffuse hyperintensity in the pons extending to the left middle cerebellar peduncle and lower midbrain (figure, A). Diffuse hyperintensity of the periventricular white matter and thickening of the pituitary stalk were also evident. Bone radiographs showed bilateral, symmetric …

Despite intensive neurophysiological research, evidence is lacking to show whether abnormal cortical excitability in migraine reflects a primary cortical disturbance or reduced control by thalamo-cortical loops. One way to contribute to the scientific discussion on this topic is to deliver transcranial magnetic stimulation (TMS) and test the cortical silent period (SP) recorded in facial muscles. The facial-muscle SP is a purely cortical phenomenon that reflects the excitability of inhibitory interneurons, and can disclose changes in cortical inhibition even in patients without documented primary lesions of the motor cortices. To test the interictal excitability of cortical motor inhibitory interneurons in migraine, we investigated the facial-SP in patients with migraine with and without aura between attacks. In 26 patients and 15 age-matched controls, high-intensity magnetic stimuli were delivered with a round coil centered at the vertex during a maximal muscle contraction. Electromyographic responses were recorded from surface electrodes placed over the subjects' perioral muscles. Facial SPs were significantly shorter in patients than in controls. The SP shortening provides neurophysiological evidence showing hypoexcitability of cortical inhibitory neurons in patients with migraine between attacks. Despite a possible primary deficit of cortical inhibitory interneurons in migraine, we favor the interpretation of a secondary disfacilitation by hypoactive thalamo-cortical loops. Based on this interpretation, the interictal reduced cortical inhibition documented by the shortened SP could be considered the motor counterpart of the reduced preactivation excitability level in the sensory cortices purported to explain why cortical evoked responses habituate poorly in patients with migraine.

Familial hemiplegic migraine (FHM) is a rare subtype of migraine with aura with an autosomal dominant pattern of inheritance. Six FHM families underwent extensive clinical and genetic investigation. The authors identified a novel ATP1A2 mutation (E700K) in three patients from one family. In the patients, attacks were triggered by several factors including minor head trauma. In one subject a 3-day coma developed after a cerebral angiography. Overall, the phenotype of the patients closely resembles that of previously reported cases of FHM type II. The E700K variant might be regarded as the cause of the disease in this family, but this was not tested functionally.

Purpose The use of inferior alveolar nerve somatosensory evoked potentials may represent an objective means of evaluating sensory nerve function in the maxillofacial region. The aim of this work was to confirm the existence of a standard sequence of prominent events in the trigeminal somatosensory evoked potentials (TSEPs) of inferior alveolar nerve (IAN) waveform, examine those components and their normal variability by statistical analysis, and discuss TSEPs’ nervous origin and some patterns of TSEPs’ abnormalities due to dysfunctional nerves. Materials and Methods TSEPs were obtained following electrical stimulation (square wave pulses 0.2 millisecond [ms] in duration, 4 to 6.5 mA, 0.7/second repetition rate, 200 averages) of the gum at the mental foramen level via intraoral surface electrodes and recorded from the contralateral central scalp sites. Results We successfully recognized steady waveforms of sufficient quality and consistently recorded a “W”-shaped response: latency onset and peak of the initial deflection of positive polarity were approximately 12 ms and 20 ms, respectively. Negative and positive deflections followed with respective peak latencies at around 26 ms and 36 ms. One side of the lower lip can be compared with the contralateral side and patients may serve as their own control in cases of unilateral nerve injury. The anaesthetic block showed the total abolition of responses. Reproducible TSEP waveform was only obtained during nerve stimulation and not during masseter muscle stimulation. Conclusions TSEPs, obtained with the present technique, may represent an objective, low-invasive, and reliable way of testing sensory nerve function in the maxillofacial region.

A rapidly progressing dementia, followed by focal neurological signs, and evidence of periodic sharp wave complexes (PSWC) in the EEG may lead to the clinical suspicion of Creutzfeldt–Jakob disease (CJD). Different clinical variants of CJD have been described in the past, with prominent extrapyramidal or occipital lobe involvement, all included in the sporadic form of CJD (sCJD). Familiar and iatrogenic forms of CJD are also known. More recently a new variant has been described, vCJD [1], casually linked to bovine spongiform encephalopathy (BSE) and it has attracted increasing attention toward each form of rapidly progressing dementia; likewise the differential diagnosis between sCJD vs. vCJD is not always easy. Magnetic resonance imaging (MRI) too seems to have a peculiar role in differentiating sCJD from vCJD, even if the role of MRI in the diagnosis of CJD is still debated. Diffusion MRI is expected to play an important role in the clinical setting of CJD, contributing to formulation of an early diagnosis, especially in cases with unusual clinical presentation. In fact, the sensitivity of diffusion MRI is superior to that of conventional MRI (T1, T2, FLAIR) in detecting specific basal ganglia and cortical abnormalities early in the course of CJD [2] and these abnormalities correlate well with areas of the most severe and characteristic neuropathological changes [3]. We describe a case of autopsy–proven sCJD, with an unusual clinical course without dementia as a presenting symptom and discuss the role of diffusion MRI and laboratory tests in making an early diagnosis.

Intracortical facilitation and inhibition, as assessed by the paired-pulse transcranial magnetic stimulation technique with a subthreshold conditioning pulse followed by a suprathreshold test pulse, was studied upon awakening from REM and slow-wave sleep (SWS). Ten normal subjects were studied for four consecutive nights. Intracortical facilitation and inhibition were assessed upon awakening from SWS and REM sleep, and during a presleep baseline. Independently of sleep stage at awakening, intracortical inhibition was found at 1-3-ms interstimulus intervals and facilitation at 7-15-ms interstimulus intervals. Motor thresholds were higher in SWS awakenings, with no differences between REM awakenings and wakefulness, while motor evoked potential amplitude to unconditioned stimuli decreased upon REM awakening as compared to the other conditions. REM sleep awakenings showed a significant increase of intracortical facilitation at 10 and 15 ms, while intracortical inhibition was not affected by sleep stage at awakening. While the dissociation between motor thresholds and motor evoked potential amplitudes could be explained by the different excitability of the corticospinal system during SWS and REM sleep, the heightened cortical facilitation upon awakening from REM sleep points to a cortical motor activation during this stage.

Summary Recovery of function after a stroke is attributable to several factors, including events in the first few days (eg, reabsorption of perilesional oedema, tissue reperfusion). However, consistent reorganisation and recovery after a stroke takes weeks or months. In the early stages, recovery from stroke can vary greatly among patients with identical clinical symptoms. Neuroimaging techniques that enable us to assess baseline and task‐related functions, and neurophysiological techniques that measure brain function in "real time", can be used to study the recovery of brain lesions after a stroke. In this review, we discuss important neuroimaging and neurophysiological studies of post‐stroke brain reorganisation.

Objective : To evaluate the usefulness, sensitivity and specificity of a new neurophysiological test for partial conduction block. Methods . In 17 patients (17 nerves) with clinical pictures strongly suggesting the presence of motor conduction block and 20 healthy subjects (40 nerves), motor nerve conduction studies were performed with the conventional surface technique and with a new technique developed by us: the single fiber EMG (SFEMG) conduction block test. Moreover, we also evaluated patients with other neurological diseases. The recent American Association of Electrodiagnostic Medicine (AAEM) consensus criteria for partial conduction block were used for the standard conduction block tests. Results : According to AAEM consensus criteria, 5/17 cases presented ‘definite' partial conduction block and 6 presented ‘probable' partial conduction block. In contrast, 16/17 cases (94%) presented evidence of conduction block at the SFEMG conduction block test. The 5/6 cases that did not fulfill in the AAEM criteria and that presented abnormal findings at SFEMG nerve conduction test could be considered affected by minimal conduction block. The sensitivity of this new test was greater than conventional test. The specificity was 100% (no abnormal findings in healthy subjects or patients with diseases other than neuropathy). Conclusions : The SFEMG conduction block test is a sensitive, complementary, technique for diagnosis of minimal conduction block in patients with normal findings in standard nerve conduction studies.

To assess the relationship between peripheral nerve involvement and the patient’s perception of his own quality of life, we studied 36 consecutive out-patients affected by insulin-dependent diabetes mellitus without other diabetic complications other than neuropathy (20 men, 16 women; mean age 39.1 years). We used clinical (Semmes-Weinstein, vibration perception threshold, muscle strength, osteotendinous reflexes), neurophysiological (sural, peroneal and ulnar nerves), metabolic (glycosylated haemoglobin) and patient-oriented (SF-36 and NASS questionnaires) measurements. Patient-oriented physical scores were significantly related to: (1) neurophysiological findings of the inferior limbs; (2) conventional measurements of sensitivity; (3) metabolic assessment. Conversely, patient-oriented mental scores were significantly related only to metabolic assessment. The patient-oriented measure provided an important perspective of the severity of the disease often closely related with the biological parameters and suggested new ways of interpreting conventional biological measurements. In particular, the peripheral nerve picture appeared strictly related with the physical aspects of the patients’ quality of life, while the metabolic picture appeared related with both the mental and physical aspects of the quality of life.

We examined the relationships between diabetic peripheral nerve involvement and patients' own perception of quality of life in a multidimensional study based on outcome research recommendations. The study enrolled 50 consecutive outpatients with type 1 diabetes mellitus (23 men, 27 women; mean age, 40.1 years). The patients were evaluated with validated clinical tests (e. g. Semmes-Weinstein, vibration perception threshold, muscle strength), neurophysiological tests (sural, peroneal and ulnar nerves) and patient-oriented (SF-36 and NASS) questionnaires. Patient-oriented physical scores were significantly related with: (1) neurophysiological findings of the lower limbs; (2) conventional measurements of sensitivity. Conversely, patient-oriented mental scores were not related with these findings. The patient-oriented questionnaires provided an important perspective of the severity of the disease, often closely related with the biological parameters. They offered new interpretations to conventional biological measurements. In particular, the peripheral nerve picture was strictly related to the physical aspects of the patients' quality of life, and not with the mental aspects.

The potential for reorganization in the adult brain has been largely underestimated in the past and we are just beginning to understand the organisational principles involved in functional recovery. A bulk of experimental evidences have been accumulated in support of the hypothesis that neuronal aggregates adjacent to a lesion in the cortical brain areas can be progressively vicarious to the function of the damaged neurones. Such a reorganisation, if occurring in the affected hemisphere of a patient with a monohemispheric lesion, should significantly modify the interhemispheric symmetry of somatotopic organisation of the sensorimotor cortices, both in terms of absolute surfaces and number of "recruited" neurons, as well as of spatial coordinates. In fact, a roughly symmetrical organisation of sensorimotor - particularly for the hand contorl - in the right and left hemisphere has been observed in healthy humans by different methods of functional brain imaging, including fMRI, TMS, MEG, HD-EEG. Not uniform results about the functional brain activity related to sensory, motor and cognitive functions in normal and diseased subjects are often due to differences in the experimental paradigm designed as well as in the spatial and temporal resolution of the neuroimaging techniques used. The multi-modal integration of data obtained with several neuroimaging techniques allowed a coherent modelling of human brain higher functions. Functional magnetic resonance imaging (fMRI) provided fine spatial details (millimetres) of the brain responses, which were compared with the cortical maps of the motor output to different body districts obtained with transcranial magnetic stimulation (TMS). Magnetoencephalography (MEG) ability to study sensorimotor areas by analysing cortical magnetic fields, is also complementary to the motor cortex topographical mapping provided by TMS. MEG high temporal resolution allows to detect relatively restricted functional neuronal pools activated during cerebral processing of external stimuli. Moreover, these brain responses can be investigated with magnetoencephalography (MEG) and high density electroencephalography (EEG) techniques, with elevated time resolution (ms). With respect to the high resolution EEG technique, the MEG technique allowed a more precise localisation of the sites of neural activity buried into the cortical sulci, but was unable to detect the response of the crown of the cortical giri and of the frontal-mesial cortex (including the supplementary motor area), because of its poor sensitivity to radially oriented dipoles. The integration of functional and anatomical information provide cues on the relationship between brain activity and anatomic sites where this takes place, allowing the characterisation of the physiological activity of the cortical brain layers as well as to study the plastic reorganisation of the brain in different pathological conditions following stroke, limb amputation, spinal cord injury, hemisperectomy.

Objective : The aim of this study was to verify the action of Botulinum toxin type-A (BoNT-A) by means of neurophysiological techniques, in patients presenting lower limb spasticity and requiring BoNT-A injections in the calf muscles, due to the poor response to medical antispastic treatment. Subjects and method : Patients presenting paraparesis were enrolled. They underwent clinical evaluation for spasticity according to the Ashworth scale and neurophysiological recordings including: motor evoked potentials (MEPs) to transcranial magnetic stimulation (TMS) of the leg area; compound motor action potential (cMAP) to tibial nerve stimulation, F-wave, and H-reflex before the treatment and 24 h, 2 weeks and 1 month after the injection of BoNT-A. In all patients, gastrocnemius was treated and in some cases soleus or tibialis posterior muscles were also injected. Results : In all patients, BoNT-A injections induced a clear clinical improvement as showed by the reduced spasticity values of the Ashworth scale. A significant increment of MEP latency and central conduction time (CCT) duration were observed 2 weeks after the treatment only in the injected muscles. Conclusions : Prolonged MEP latencies and CCT after BoNT-A injections is probably due to a central alteration in responsiveness of spinal motor neurons to descending impulses from the corticospinal tracts. Such changes represent objective parameters heralding clinical efficacy of treatment.

We simultaneously performed near infrared spectroscopy (NIRS) and transcranial Doppler (TCD) to evaluate the effects of hypercapnia as well as of scalp ischemia on the blood flow at two different depth levels within the brain and of the scalp vessels. A decrease in the backscattered light intensity, meaning an increment of blood volume, was detected at the end of hypercapnia in all healthy subjects. This decrement was partly masked by ischemia in the cutaneous vessels. In 2 patients with a monohemispheric lesion in the middle cerebral artery (MCA) territory, an increase in NIRS response was found in the healthy hemisphere, while in the stroke side the CO2-induced changes were negligible. TCD data showed a similar increment of blood flow velocity to the hypercapnia in both hemispheres, with no differences between the affected and normal side in 1 patient, whereas in the second one, no increment was observed on the affected side, probably due to internal carotid artery stenosis. The two methods nicely integrate: TCD mainly tests subcortical changes in the MCA flow, while NIRS is exquisitely sensitive to cortical arterioles and capillary blood flow modifications.

Motor evoked potentials (MEPs) to magnetic transcranial stimulation (TCS) were simultaneously and bilaterally recorded from flexor carpi radialis (FCR) and extensor communis digitorum (ECD) muscles in seven healthy and trained subjects. Latencies and amplitudes characteristics of MEPs were investigated under the following randomised conditions: muscular and mental relaxation; mental simulation, during absolute muscular relaxation, selective flexion or extension of the right or left wrist muscles; arithmetical calculation with muscular relaxation. Unspecific, diffuse facilitatory effects on MEPs amplitude were induced by mental non motor activity (arithmetical calculation). A further specific and lateralised amplitude potentiation on the agonist muscle acting as 'prime mover' for the mentally simulated movement was consistently found in all the subjects, without significant latency changes. Inhibitory effects on antagonists were evident only in two subjects.

Background and purpose The thalamus seems to be profoundly involved in the cyclical recurrence of migraine clinical and neurophysiological features. Here possible structural changes in the thalamus of migraineurs were searched for by means of diffusion tensor (DT) magnetic resonance imaging (MRI). This MRI technique provides quantitative data on water molecule motion as a marker of tissue microstructure. Methods Twenty-four untreated migraine without aura (MO) patients underwent DT-MRI scans (3-T Siemens Gyroscan) during (n = 10) and between attacks (n = 14) and were compared with a group of 15 healthy volunteers (HVs). Fractional anisotropy (FA) and mean diffusivity (MD) were examined. Results During the interictal phase MO patients had a significantly higher FA and slightly lower MD values in bilateral thalami compared with HVs. During attacks, all MRI quantitative measurements in migraineurs were similar to those found in HVs. Right thalamic FA was positively correlated with the number of days since the last migraine attack in pooled patient data (r = 0.626, P = 0.003). Conclusions These higher thalamic FA values noted during the interictal period which normalized during an attack are probably related to plastic peri-ictal modifications in regional branching and crossing of fibres. Whether these changes could be considered as the anatomical counterpart of the cyclical functional fluctuations previously observed in the neurophysiology of migraine remains to be determined.

We report a mentally retarded 30-year-old woman with partial trisomy of chromosome 9 (46, XX-6, +der(6)t(6,9)pat) who has had epilepsy since age 11 months. She had been treated with various combinations of drugs. After 1 year of treatment with valproate (VPA) and ethosuximide (ESM), the patient developed arthralgias, muscle weakness, fatigue, and fever. Laboratory examination showed increased sedimentation rate, hypergammaglobulinemia, and high titers of antinuclear antibodies (ANA). The possibility of VPA-induced systemic lupus erythematosus (SLE) was considered. This diagnosis was supported by detection of antihistone antibodies and the HLA-DR4 antigen. VPA dosage was tapered and discontinued, with accompanying resolution of clinical, immunological and hematological signs of SLE 6 weeks after VPA discontinuation. This is the fourth reported case of VPA-induced SLE.

Background and objectives Studies of spontaneous EEG and visual or somatosensory evoked high frequency oscillations indicate that the abnormal fluctuations of cortical responsivity over time in relation to the migraine attack could be due to abnormal thalamic control. Here we searched for possible structural changes in the thalamus of migraineurs by mean of acquiring diffusion tensor magnetic resonance imaging (MRI). This MRI technique provides quantitative data on water molecular motion, as a marker of tissue structure. Materials & Method – Seventeen untreated migraine without aura (MO) patients underwent MRI scan (3-Tesla Siemens Gyroscan) during (n=7) and between attacks (n=10) and were compared to a group of 14 healthy volunteers (HV). We examined fractional anisotropy (FA) and mean diffusivity (MD) in the thalamus.

We studied retrospectively the intraoperative preresection electrocorticograms (ECoGs) of 72 patients undergoing surgery for medically intractable, mostly complex partial, temporal lobe seizures (TLS). Quantification of interictal epileptiform discharges (EDs) detected visually at each electrode location in 2 min recording epochs included computations of ED rates (EDs/min) and cumulative voltages (CuVs) (μV/min). Of 6388 EDs, 81% involved the infratemporal surface, 18% the lateral temporal surface and 1% the orbital frontal area. Forty-eight patients (67%) demonstrated multiple (up to 5 or more), temporally independent foci. Dominant foci in medial and lateral infratemporal locations were about equally common and were significantly more frequent than in lateral temporal locations. Rankings of ED CuVs and rates at individual cortical locations defined 4 areas of “relative interictal cortical epileptogenicity.” These were arranged in an orderly pattern with the anterior parahippocampal gyrus and the inferomedial surface of the temporal tip displaying the highest and the lateral temporal and posterior infratemporal cortices showing the lowest propensity to the interictal epileptiform discharge. Individual areas were not characterized by distinct clinical seizure manifestations. Preresection ECoGs provide information on the epileptogenic dysfunction that involves most of the temporal lobe of patients with medically intractable TLS.

A patient affected by familial hemiplegic migraine underwent Transcranial Doppler Sonography twice: the first during a spontaneous attack with right hemiparesis and aphasia, the second during a headache-free period. During the attack the following haemodynamic changes were seen: (a) bilateral increase in the middle cerebral artery and anterior cerebral artery blood flow velocities (this increase was more pronounced on the left side), (b) decreased systo-diastolic ratio and pulsatility index on the right side, (c) increased systo-diastolic ratio and pulsatility index on the left side. Our results indicate that during the attack in this familial hemiplegic migraine patient a diffuse vasoconstriction of the basal cerebral arteries developed. Moreover, Transcranial Doppler Sonography data suggest that a prolonged vasoconstriction of the peripheral arterioles could play a role in determining the neurological symptoms in this syndrome.

BackgroundPrevious studies with Transcranial Magnetic Stimulation (TMS) have focused on the cortical representation of limited group of muscles. No attempts have been carried out so far to get simultaneous recordings from hand, forearm and arm with TMS in order to disentangle a 'functional' map providing information on the rules orchestrating muscle coupling and overlap. The aim of the present study is to disentangle functional associations between 12 upper limb muscles using two measures: cortical overlapping and cortical covariation of each pair of muscles. Interhemispheric differences and the influence of posture were evaluated as well.Methodology/principal findingsTMS mapping studies of 12 muscles belonging to hand, forearm and arm were performed. Findings demonstrate significant differences between the 66 pairs of muscles in terms of cortical overlapping: extremely high for hand-forearm muscles and very low for arm vs hand/forearm muscles. When right and left hemispheres were compared, overlapping between all possible pairs of muscles in the left hemisphere (62.5%) was significantly higher than in the right one (53.5% ). The arm/hand posture influenced both measures of cortical association, the effect of Position being significant [p = .021] on overlapping, resulting in 59.5% with prone vs 53.2% with supine hand, but only for pairs of muscles belonging to hand and forearm, while no changes occurred in the overlapping of proximal muscles with those of more distal districts.Conclusions/significanceLarger overlapping in the left hemisphere could be related to its lifetime higher training of all twelve muscles studied with respect to the right hemisphere, resulting in larger intra-cortical connectivity within primary motor cortex. Altogether, findings with prone hand might be ascribed to mechanisms facilitating coupling of muscles for object grasping and lifting -with more proximal involvement for joint stabilization- compared to supine hand facilitating actions like catching. TMS multiple-muscle mapping studies permit a better understanding of motor control and 'plastic' reorganization of motor system.

Background Recent evidence indicates that peripheral tissue markers can provide information regarding changes affecting cellular metabolism in Alzheimer disease (AD). We previously reported that serum copper levels can discriminate subjects with AD from normal control subjects (with 60% sensitivity and 95% specificity) and from patients with vascular dementia (with 63% sensitivity and 85% specificity). Objective To study the correlation between AD and serum levels of transition metals and markers of peripheral oxidative stress. Design Case study. Setting General hospital inpatient wards and outpatient clinics. Patients A pair of elderly monozygotic female twins discordant for AD. Main Outcome Measures Biochemical analyses of peripheral-blood transition metals and indicators of oxidative stress and neurologic and neuropsychological assessments of clinical status for presence of cognitive impairment and AD. Results Serum copper and total peroxide levels were both 44% higher in the twin with greater cognitive impairment and a diagnosis of AD. Conclusions The cases reported support the hypothesis of a major involvement of copper and oxidative abnormalities in AD.

Early auditory evoked potentials and electroencephalograms were recorded in 10 rabbits during hypoxic hypoxia (5% O2 in N2 gas mixture) and after reoxygenation. In all experiments EEG flattening preceded the disappearance of the early evoked potential, whose recovery after reoxygenation was more rapid than that of the EEG. Significant increases in P3-P4 and P1-P3 interpeak latencies were observed during hypoxic conditions before the complete flattening of the early auditory evoked potential. In addition, negative relationships were found between the P3-P4 interpeak latency increase and mean arterial pressure reduction, and between the former and metabolic acidosis.

Study Objectives: The aim of the study is to assess, in humans, transcallosal inhibition upon awakening from rapid eye movement (REM) and non-REM sleep, by paired-pulse transcranial magnetic stimulation (TMS). Design: During the daytime, a baseline session of motor evoked potentials (MEPs) was recorded. During the nighttime, the TMS sessions were administered just before sleep onset and upon awakenings from REM and stage 2 sleep, both in the early and final part of night. Setting: The sleep research laboratory at the University of Rome "La Sapienza." Participants: Ten right-handed subjects participated in the experiment for 4 consecutive sleep-recording nights. Interventions: N/A. Measurements and Results: During the daytime, a robust transcallosal inhibition was found; the MEP amplitude reduction ranged from 35% to 40%. During the nighttime, a decrease of transcallosal inhibition from right-to-left motor cortex, as compared to that from left-to-right motor cortex, was observed. The direct assessment of MEP changes, as a function of sleep stage and of the time of night, pointed to a drop of transcallosal inhibition after awakening from REM sleep. Therefore, the inhibitory activity of transcallosal fibers observed after non-REM awakening almost disappeared after REM sleep awakenings. Conclusions: The drastic drop of transcallosal inhibition after awakenings from REM sleep represents the first evidence in humans of a change of interhemispheric connectivity mediated by the corpus callosum during this sleep stage and may open new avenues for a better understanding of some aspects of sleep mechanisms (ie, dreaming function and dream mentation). Abbreviations: REM, rapid eye movement; MEP, motor evoked potentials; TMS, transcranial magnetic stimulation; EEG, electroencephalogram; ADM muscle, Abductor Digiti Minimi muscle; ISI, interstimulus intervals; MT, motor threshold; IHPP paradigm, interhemispheric paired pulse paradigm; ANOVA, analysis of variance.