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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Green tea polyphenol extract attenuates zymosan-induced non-septic shock in mice.

Multiple-organ failure (MOF) is defined as the progressive deterioration in function which occurs in several organs or systems in patients with septic shock, multiple trauma, severe burns, or pancreatitis. In the present study, we have investigated the effects of Green Tea extract (GTE) on the development of general inflammation caused by zymosan (500 mg/kg, administered i.p. as a suspension in saline) in mice. Organ failure and systemic inflammation in mice was assessed 18 hours after administration of zymosan and/or GTE and monitored for 12 days (for loss of body weight and mortality). Treatment of mice with GTE (25 mg/kg i.p., 1 and 6 hours after zymosan) attenuated the peritoneal exudation and the migration of polymorphonuclear cells (PMNs) caused by zymosan, GTE also attenuated the lung, liver and pancreatic injury and renal dysfunction caused by zymosan as well as the increase in myeloperoxidase (MPO) activity caused by zymosan in the lung and intestine. Immunohistochemical analysis for inducible nitric oxide synthase (iNOS), nitrotyrosine and poly(ADP-ribose) (PAR) revealed positive staining in lung and intestine tissues obtained from zymosan-treated mice. The degree of staining for nitrotyrosine, iNOS and PAR were markedly reduced in tissue sections obtained from zymosan-treated mice, which received GTE. In conclusion this study provides evidence, for the first time, that GTE attenuates the degree of zymosan induced generalized inflammation in mice.

Short communication: impairment of membrane markers on peripheral blood mononuclear cells and imbalance of cytokine secretion in the pathogenesis of multiple sclerosis active phases.

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). In active disease, a transmigration of autoreactive T cells to myelin antigens recruited from the peripheral blood (PBMC) to the CNS occurs, and there these cells prolong their survival and contribute to the perpetuation of the inflammation. In the active local lesions of MS patients, these cells display activation and apoptosis surface markers and secrete a range of cytokines. The aim of this research is to study on PBMCs and in the serum of stable and active MS subjects (1) the behavior of the CD40/CD40L system and the consequent balance of Th1 and Th2 cytokines and (2) the apoptosis marker system CD95/CD95L and tumor necrosis factor (TNF)- binding receptors, TNFRI and TNFRII. A possible excess of activation marker expression affecting and driving Th1 cytokine production or a parallel impairment of apoptosis may contribute to MS relapses. Our results may indicate that a dysregulation of early activation and apoptosis receptor systems and a profound and complex imbalance of cytokine production occurred in the peripheral blood of MS patients. This impairment could account for active phases of the disease.

Ictal and interictal hypoactivation of the occipital cortex in migraine with aura. A neuroimaging and electrophysiological study.

In recent studies, several authors have highlighted and studied an altered blood oxygenation level dependent (BOLD) signal in subjects affected by migraine with aura, using functional magnetic resonance imaging (fMRI) during the migraine attack or during the period between two attacks. Using fMRI, we assessed a 27-year-old man affected by migraine with aura at two different times: during the migraine attack, and a fortnight later, in order to look for differences in regional cerebral blood flow after visual stimulation. In addition, during the attack-free period we carried out a series of electrophysiological examinations. Our results demonstrate different activation patterns of the occipital cortex during the asymptomatic period and during the migraine attack. Furthermore, the electrophysiological data obtained demonstrated altered activity due to the patient's disease.

Migraine with and without aura: electrophysiological and functional neuroimaging evidence.

The neuropathological processes believed to underlie migraine with and without aura are still widely debated in the literature. In order to arrive at a more detailed and comprehensive picture of the altered processes present in migraineurs, electrophysiological data obtained through transcranial magnetic stimulation (TMS) and electroencephalography (EEG) were combined with haemodynamic data obtained through functional magnetic resonance imaging (fMRI). Ten subjects affected by migraine (with or without aura) underwent TMS and EEG investigation prior to a visual stimulation task, studied in fMRI. Our preliminary results showed a reduced cortical silent period especially in subjects affected by migraine with aura. The fMRI BOLD response was found to be weaker in occipital areas proportionally to the frequency and severity of migraine attacks. The data obtained from our study seem to support the theory of cortical spreading depression recently observed in human subjects. Moreover, the electrophysiological data were also correlated to migraine attack frequency, thus pointing to elevated cortical excitability between attacks. Better understanding of the neuropathological processes that trigger migraine attacks will help in the selection of more adequate prophylactic therapies. The results of this preliminary study need to be confirmed in a a large sample of subjects.

Quality of life of patients with telemetric pumps for intrathecal baclofen infusion: data and limitations of assessment scales.

Over the past three decades, telemetric pumps have been used for the infusion of intrathecal baclofen in patients with severe spasticity, but the correlation between pump implantation and quality of life (QoL) has rarely been studied. The aim of this study was therefore to quantify QoL in these patients. We assessed 15 candidates for intrathecal baclofen infusion pump implantation using three scales: Self-Evaluation of Life Function, Quality of Life Index, and Quality of Well-Being Scale. These scales were administered a week before pump implantation and 12 months after reaching the optimal dosage. The first scale revealed a significant increase in QoL, whereas on the other two the increase was not significant. These results encourage us to continue this study in a larger patient sample, considering different types of pathology and presence/absence of caregivers.

Cortical silent period prolongation in spinocerebellar ataxia type 2 (SCA2).

Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominant neurodegenerative disorder mapped on chromosome 12. Different results have been reported in spinocerebellar ataxias following transcranial magnetic stimulation (TMS). TMS-induced cortical silent period (CSP) was prolonged in different cerebellar disorders. Here we evaluate the duration of the TMS-induced CSP following a single magnetic stimulus in a large homogeneous group of SCA2 patients compared with idiopathic cerebellar ataxia (IDCA) patients with similar disease duration and severity, and in 20 healthy controls. The CSP duration in both arm and leg muscles was significantly (p<0.005) longer in patients than in controls. A significant positive correlation between disease duration and CSP prolongation in both SCA2 and IDCA was found. No correlation between age, onset and CSP duration emerged in either group. This study shows a prolongation of the TMS-induced silent period in both SCA2 and IDCA indicating that the cortical inhibitory mechanism is dependent on the disease duration and severity. Thus, the cerebellum seems to exert a pliable physiological influence on the cortico-spinal system through control of inhibitory cortical interneurons.