Semi-Automatic Analysis of Specific Electroencephalographic Patterns during NREM2 Sleep in a Pediatric Population after SARS-CoV-2 Infection.

The post-COVID-19 condition is defined by the World Health Organization as the persistence of symptoms or development of new symptoms three months after the initial SARS-CoV-2 infection, lasting for at least two months without a clear explanation. Neuropsychiatric disorders associated with this condition include asthenia, memory and concentration problems, and sleep disturbances. Our study aims to investigate sleep patterns following SARS-CoV-2 infection using EEG findings and a sleep quality questionnaire completed by parents (Sleep Disturbance Scale for Children-SDSC). Notably, our investigation is based on a convenience sample. The patients in our sample, aged 1 to 14 years, are not currently taking any medications; rather, they are undergoing follow-up assessments at the Child Neuropsychiatry department of the University Hospital of Messina for neurodevelopmental evaluations. Specifically, we are analyzing amplitude and power spectrum data in the first five minutes of NREM2 sleep, calculated from EEG recordings obtained via bipolar leads within three months after the onset of the disease. These results will be compared with controls performed on the same subjects in the six months preceding the infection. The focus of the study was sleep spindles, which are generated by the thalamocortical systems and play a role in sleep modulation, memory, and learning. Preliminary analysis suggests a predominant increase in the slow component of the spindles in the right-frontal lead.

EEG Patterns in Patients with Prader-Willi Syndrome.

Prader-Willi syndrome (PWS) is a rare disease determined by the loss of the paternal copy of the 15q11-q13 region, and it is characterized by hypotonia, hyperphagia, obesity, short stature, hypogonadism, craniofacial dysmorphisms, and cognitive and behavioral disturbances. The aims of this retrospective study were to analyze interictal EEG findings in a group of PWS patients and to correlate them with genetic, clinical, and neuroimaging data. The demographic, clinical, genetic, EEG, and neuroimaging data of seventy-four patients were collected. Associations among the presence of paroxysmal EEG abnormalities, genotype, and clinical and neuroimaging features were investigated. Four patients (5.4%) presented drug-sensitive epilepsy. Interictal paroxysmal EEG abnormalities-focal or multifocal-were present in 25.7% of the cases, and the normalization of the EEG occurred in about 25% of the cases. In 63.2% of the cases, the paroxysmal abnormalities were bilaterally localized over the middle-posterior regions. Brain magnetic resonance imaging (MRI) was performed on 39 patients (abnormal in 59%). No relevant associations were found between paroxysmal EEG abnormalities and all of the other variables considered. Interictal paroxysmal EEG abnormalities-in particular, with a bilateral middle-posterior localization-could represent an important neurological feature of PWS that is not associated with genotype, cognitive or behavioral endophenotypes, MRI anomalies, or prognosis.

Multiple sclerosis, solitary sclerosis or something else?

BACKGROUND: Inflammatory demyelinating diseases of the central nervous system represent a wide spectrum of entities and their classification cannot currently be regarded complete. OBJECTIVE: Our aim is to describe a series of patients presenting with progressive myelopathy associated to a single demyelinating lesion of the spinal cord. METHODS: We identified the patients affected by chronic progressive spinal cord dysfunction related to a single spinal cord lesion not satisfying the diagnostic criteria for any of the currently defined diseases. RESULTS: Seven females and one male were included. The median age at onset of symptoms was 53 years (range 42-68) and the median follow-up was 8 years (range 5-12). Brain and spinal magnetic resonance imaging (MRI) scans detected only one single, circumscribed, T2 hyperintense, non-longitudinally extensive lesion at level of cervico-medullary junction or cervical cord, in the absence of Gadolinium enhancement or swelling. Cerebrospinal fluid (CSF) examination displayed neither oligoclonal bands nor raised IgG index. A response to immunosuppressive agents was observed in some of the patients. Serial control brain and spinal MRI did not reveal accumulation of new lesions. CONCLUSION: New entities or variants should be included among the inflammatory demyelinating diseases of the central nervous system, and their characterization may have relevant prognostic and treatment implications.

Anterior tarsal tunnel syndrome: a misunderstood and a misleading entrapment neuropathy.

Anterior tarsal tunnel syndrome (ATTS) is a rare entrapment neuropathy of the deep peroneal nerve beneath the extensor retinaculum on the top of the ankle. ATTS is often asymptomatic or olygosymptomatic. There are few reports describing the ATTS. We describe the clinical and electrophysiological features of 85 patients with unilateral or bilateral ATTS prospectively collected between January 2000 and December 2010 in our laboratory of Clinical Neurophysiology. This entrapment neuropathy remains poorly diagnosed and it might be misleading when performing a diagnostic EMG-ENG examination for suspected polyneuropathy or lumbosacral radiculopathy.

Role of electron microscopy in the diagnosis of cadasil syndrome: a study of 32 patients.

BACKGROUND AND PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is caused by NOTCH3 gene mutations that result in vascular smooth muscle cell (VSMC) degeneration. Its distinctive feature by electron microscopy (EM) is granular osmiophilic material (GOM) detected in VSMC indentations and/or the extracellular space close to VSMCs. Reports of the sensitivity of EM in detecting GOM in biopsies from CADASIL patients are contradictory. We present data from 32 patients clinically suspected to have CADASIL and discuss the role of EM in its diagnosis in this retrospective study. METHODS: Skin, skeletal muscle, kidney and pericardial biopsies were examined by EM; the NOTCH3 gene was screened for mutations. Skin and muscle biopsies from 12 patients without neurological symptoms served as controls. RESULTS AND DISCUSSION: All GOM-positive patients exhibited NOTCH3 mutations and vice versa. This study i) confirms that EM is highly specific and sensitive for CADASIL diagnosis; ii) extends our knowledge of GOM distribution in tissues where it has never been described, e.g. pericardium; iii) documents a novel NOTCH3 mutation in exon 3; and iv) shows that EM analysis is critical to highlight the need for comprehensive NOTCH3 analysis. Our findings also confirm the genetic heterogeneity of CADASIL in a small Italian subpopulation and emphasize the difficulties in designing algorithms for molecular diagnosis.

Diagnostic difficulties with central nervous system actinomycosis.

When faced with expanding brain lesions of unknown origin showing a ring-shaped enhancement on post-contrast imaging, we use definite criteria to direct further investigation and distinguish among a number of possible diagnostic hypotheses. However, a correct diagnosis may be difficult in some cases, especially when dealing with less frequent conditions. This is the case of actinomycosis, a highly treatable but insidious infection for which nowadays there may be a low level of attention. Brain localization is associated with a significant morbidity and may represent a true diagnostic pitfall. Here we report the difficulties encountered with a case of central nervous system actinomycosis.

Familial hemifacial spasm and determinants of late onset.

The role of hypertension in the late onset of hemifacial spasm (HFS) is evaluated in a family, spanning four generations. Magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) revealed a variable anatomical relationship between nervous and vascular structures in the symptomatic cerebello-pontine angle. In one case, showing neurovascular conflict (NVC), microvascular surgical decompression was followed by clinical resolution of HFS. Neuroimaging suggesting NVC was found in all symptomatic patients of the last two generations and in three younger subjects not affected by HFS. As a determinant for the late development of clinical expression is reviewed the role of arterial hypertension, detected few years before HFS appearing in all symptomatic subjects. The distribution of NVC in several members of the same family suggests a genetic susceptibility towards vascular anomaly.

Lennox-Gastaut syndrome with late-onset and prominent reflex seizures in trisomy 21 patients.

PURPOSE: Lennox-Gastaut syndrome (LGS) is a severe epileptic condition characterized by multiple seizure types including tonic seizures, slow spike-and-wave discharges on electroencephalography (EEG), and cognitive impairment. LGS can occur in apparently healthy subjects or in patients with preexisting brain damage. The onset peaks between 3 and 5 years of age and the prognosis is usually poor. Herein we report 13 subjects with trisomy 21 who developed LGS. METHODS: We retrospectively reviewed the clinical and EEG data of consecutive patients with LGS and trisomy 21 referred to five epilepsy centers over the last 30 years. RESULTS: Data for 13 patients (8 male, 5 female) were collected. The mean age at onset was 9.1 years (range 5-16). The mean age at last follow-up was 23.5 years (range 11-43 years). Seizure onset was after age 8 years in eight (62%) patients and between age 5 and 8 in the other five. In none of the cases did a West syndrome precede the onset of LGS. Nine of 13 patients (69%) had unambiguous reflex seizures, mostly precipitated by sudden unexpected sensory stimulations, usually preceding or accompanying the onset of a full-blown LGS picture. Interictal and ictal EEG findings were typical for LGS. All patients were drug-resistant. DISCUSSION: Patients with trisomy 21 may present a peculiar LGS, characterized by late onset and high occurrence of reflex seizures. Mechanisms underlying this particular presentation of LGS may include dendritic rarefaction and decreased interneurons, as well as functional abnormalities leading to overall decreased brain inhibition in these patients.

Description of a family with a novel progressive myoclonus epilepsy and cognitive impairment.

We report a family of Algerian origin presenting an unusual, severe form of progressive myoclonus epilepsy characterized by myoclonus, generalized tonic-clonic seizures and moderate to severe cognitive impairment, with probable autosomal recessive inheritance. Disease onset was between 6 and 16 years of age. The diagnosis of Unverricht-Lundborg disease and all other known causes of progressive myoclonus epilepsies were excluded by specific laboratory tests and molecular analysis.

Sertraline in the treatment of depressive disorders in patients with Parkinson's disease.

We studied 54 idiopathic Parkinson's disease (PD) patients with depressive disorders (DD) to compare the efficacy and the effect of treatment with sertraline in the usual formulation and in the liquid oral concentrate (LOC) formulation. After 6 months of sertraline treatment, the Hamilton Depression Rating Scale and the Montgomery and Asberg Depression Rating Scale showed a decrement (p<0.001, for both formulations). Parkinson's Disease Questionnaire scores improved (p<0.005 for usual formulation and p<0.001 for LOC formulation), as did Clinical Global Impression-Severity of Illness scale and Clinical Global Impression-Global Improvement scale scores (p=0.1, for both formulations). Mini Mental State Examination and Unified Parkinson's Disease Rating Scale motor subscores did not change. These results suggest that sertraline LOC may also be a useful treatment for DD in PD patients, especially for those with swallowing problems, and have significant benefit for quality of life, without worsening of parkinsonian features.

Ictal paresis associated to PLEDS in two children: a video-EEG study.

Ictal paresis (IP) is a rare negative motor phenomenon presenting challenging differential diagnostic problems with transient ischemic attacks, post-ictal paralysis, migraine and psychogenic paralysis. Video-EEG undoubtedly represents the essential mean for a proper diagnosis. Periodic lateralised epileptiform discharges (PLEDs) are a distinctive EEG pattern, consisting of periodic spike or sharp wave discharges, often associated with seizures. It is under debate if PLEDs should be considered only a peri-ictal or also an ictal EEG pattern. We describe two children with severe focal epilepsies, who presented IP recorded during video-EEG monitoring, associated to PLEDs. Clinical observation along with interictal and ictal scalp-EEG findings, suggested a fronto-temporal seizure onset in the first, and a temporo-insular onset in the second. We confirm that PLEDs may be an ictal pattern associated with negative motor phenomena.

Etanercept reduces acute tissue injury and mortality associated to zymosan-induced multiple organ dysfunction syndrome.

It has been well demonstrated that TNF-alpha is integral to the pathogenesis of multiple organ dysfunction syndrome (MODS). In this study, we investigate the effects of etanercept (10 mg/kg, s.c.), a specific TNF-alpha-soluble inhibitor, on the acute phase and late mortality in a murine model of MODS of nonseptic origin induced by zymosan (500 mg/kg, suspended in saline solution, i.p.). Etanercept was administered 1 h after the injection of zymosan. Animals were killed after 18 h. In another set of experiments, mice were monitored for systemic toxicity, loss of body weight, and mortality for 12 days. Sham-treated and TNF receptor 1 (TNFR1)-deficient animals were used as control. Treatment of mice with Etanercept and TNFR1 gene deletion decreased the peritoneal exudation and the migration of neutrophils caused by zymosan. In addition, pharmacological and genetic neutralization of TNF-alpha attenuated pancreas and ileum injury (histology), the increase in myeloperoxidase activity in the ileum and in the lung, and the formation of TNF-alpha and IL-1beta. Immunohistochemical analysis for TNF-alpha, transforming growth factor beta, and vascular endothelial growth factor revealed a positive staining in pancreas and ileum sections. The degree of immunostaining was markedly reduced after etanercept treatment and in TNFR1 knockout mice. Furthermore, TNF-alpha neutralization decreased the potent apoptotic stimulus induced by zymosan. All of these findings ultimately led to an amelioration of organ functions at 18 h and to a better survival rate at 12 days. Therefore, we demonstrate that etanercept reduces acute tissue injury and mortality associated to MODS of nonseptic origin in mice.

Quantitative analysis of pursuit ocular movements in Parkinson's disease by using a video-based eye tracking system.

The purpose of this study is to assess the efficacy and the tolerability of a new vision-based non-intrusive eye tracker in a population composed of normal controls and in patients affected by nonadvanced Parkinson's disease (PD). PD patients characteristically have difficulty in sustaining repetitive motor actions. Previous studies showed a progressive bradykinesia and hypokinesia of pursuit ocular movements (POM) in advanced PD. We found that the values of POM were lower in PD patients than in normal controls (p < 0.001). In PD patients, the values correlated closely with Hoehn and Yahr stage and Unified Parkinson Disease Rating Scale motor subscore (p < 0.001, for both). Our data suggest that deficit in POM occurs also in nonadvanced PD patients and it is closely correlated with clinical scores. Thus, this vision-based system can be considered a new method to provide, noninvasively, measures of POM dysfunctions and can be used as reliable indices of disease severity in PD patients.

Role of endogenous glutathione in the secondary damage in experimental spinal cord injury in mice.

GSH plays multiple roles in the nervous system including free radical scavenger, redox modulator of ionotropic receptor activity, and possible neurotransmitter. A lot of evidence suggests that GSH is involved in the pathogenesis of neurodegenerative disorders, like spinal cord injury (SCI). This study was undertaken to determine if the inhibition of endogenous glutathione, by L-buthionine-(S,R)-sulfoximine (BSO), affords protection against peroxynitrite-mediated toxicity in response to the spinal cord injury in vivo. The spinal cord of damaged animals showed a significant elevation of biochemical, immunohistochemical and functional parameters, increasing, respectively, neutrophils infiltration, lipid peroxidation, nitrotyrosine formation, PAR expression, apoptosis (measured by TUNEL staining) and loss of hind legs movement in SCI-operated mice. In contrast, the administration of BSO led to worsening of this already compromised setting, increasing the degree of (1) neutrophil infiltration, (2) lipid peroxidation, (3) histological damage, (4) apoptosis, (5) nitrotyrosine formation, (6) PAR expression, (7) apoptosis (measured by TUNEL staining) and (7) loss of hind legs movement. Thus, endogenous glutathione plays an important protective role against secondary damage after SCI.

Hallucinations after abrupt withdrawal of oral and intrathecal baclofen.

Since 1977 several cases of hallucinations after abrupt withdrawal of oral baclofen have been described. There are no reports of hallucinations after gradual withdrawal of oral baclofen. No one has ever described visual hallucinations after abrupt interruption of intrathecal baclofen therapy. We describe five personally observed cases of visual hallucinations occurring after sudden interruption of baclofen (in two of these cases, intrathecal baclofen) therapy. The patients were immediately submitted to routine EEG, visual evoked potentials and standard brain magnetic resonance imaging (MRI). A few days later they also underwent polysomnography, fundus oculi examination and brain MRI of the temporal lobe. All these examinations were normal. We hypothesise that these symptoms could be due to biochemical and molecular changes, chiefly in glutamatergic n-methyl-d-aspartate, GABA-A, and GABA-B receptor response, leading to increased excitability and spontaneous activity as a result of chronic use of baclofen.

Effects of combination of melatonin and dexamethasone on secondary injury in an experimental mice model of spinal cord trauma.

This study investigates the effects of combination therapy with melatonin and dexamethasone on the degree of spinal cord injury caused by the application of vascular clip in mice. Spinal cord injury in mice resulted in severe trauma, characterized by edema, neutrophil infiltration, and apoptosis (measured by terminal deoxynucleotidyltransferase-mediated UTP end labeling staining, and immunoreaction of Bax, Bcl-2, and Fas Ligand). Infiltration of the spinal cord tissue with neutrophils (measured as increase in myeloperoxidase activity) was associated with enhanced immuno- histochemical and functional alterations revealed, respectively, by an increased of tumor necrosis factor (TNF)-alpha immunoreactivity, NOS as well as nitrotyrosine and loss of hind leg movement in spinal cord injury (SCI)-operated mice. In contrast, the degree of neutrophil infiltration at different time points, cytokine expression, histologic damage iNOS expression, apoptosis, was markedly reduced in the tissues obtained from SCI-treated mice with the combination therapy, and the motor recovery was also ameliorated. No anti-inflammatory effect was observed in animals treated with melatonin (10 mg/kg) or with dexamethasone (0.025 mg/kg) alone. This study shows that the combination therapy with melatonin and dexamethasone reduces the degree of secondary damage associated with spinal cord injury in mice, and supports the possible use of melatonin in combination with steroids to reduce the dose and the side effects related with the use of steroids for the management of inflammatory disease.