COGNITIVE IMPAIRMENT IN PATIENTS WITH PARKINSON’S DISEASE

TRANSCRANIAL DIRECT CURRENT STIMULATION FOR TREATMENT OF FREEZING OF GAIT IN PARKINSON’S DISEASE. A CROSS-OVER STUDY

Transcranial magnetic stimulation reveals cortical hyperexcitability in episodic cluster headache

Abstract Evidence shows involvement of the cerebral cortex in the pathophysiology of cluster headache (CH). Here we investigated cortical excitability in episodic CH patients by using transcranial magnetic stimulation. In 25 patients with episodic CH and 13 healthy subjects we evaluated the motor cortical response to single-pulse (ie, motor threshold, input-output curves, cortical silent period) and paired-pulse (ie, intracortical facilitation, short intracortical inhibition) transcranial magnetic stimulation in both hemispheres. Thirteen patients were evaluated outside bout and the remaining 12 patients inside bout. Our results showed increased slope of the input-output curves after stimul…

Is Transcranial Magnetic Resonance Imaging-Guided Focused Ultrasound a Repeatable Treatment Option? Case Report of a Retreated Patient With Tremor Combined With Parkinsonism

Introduction In recent years, transcranial Magnetic Resonance Imaging-guided Focused Ultrasound (tcMRgFUS) treatments for functional neurological disorders are giving a new thrust to the field of therapeutic brain lesioning. Objective To present the case of a patient affected by tremor combined with Parkinsonism who underwent a second tcMRgFUS thalamotomy because of relapsing tremor after a few months from the first tcMRgFUS treatment. Methods A 72-yr-old, right-handed man, came to our observation because of a disabling tremor affecting his upper limbs, refusing any invasive surgical procedure and already treated by tcMRgFUS left Vim thalamotomy. However, clinical benefit had brief duration…

Intracortical facilitation within the migraine motor cortex depends on the stimulation intensity. A paired-pulse TMS study

Abstract Introduction Connectivity within the primary motor cortex can be measured using the paired-pulse transcranial magnetic stimulation (TMS) paradigm. This evaluates the effect of a first conditioning stimulus on the motor evoked potential (MEP) elicited by a second test stimulus when different interstimulus intervals are used. Aim of the present study was to provide, in patients suffering from migraine without aura (MwoA), additional information on intracortical facilitation (ICF), short intracortical inhibition (SICI), and long intracortical inhibition (LICI), using different intensities of the test stimulus (TS). Methods We enrolled 24 patients with episodic MwoA and 24 age- and sex…

THE PALMOMENTAL REFLEX IN AMYOTROPHIC LATERA SCLEROSIS

A new p65 isoform that bind the glucocorticoid hormone and is expressed in inflammation liver diseases and COVID-19

AbstractInflammation is a physiological process whose deregulation causes some diseases including cancer. Nuclear Factor kB (NF-kB) is a family of ubiquitous and inducible transcription factors, in which the p65/p50 heterodimer is the most abundant complex, that play critical roles mainly in inflammation. Glucocorticoid Receptor (GR) is a ligand-activated transcription factor and acts as an anti-inflammatory agent and immunosuppressant. Thus, NF-kB and GR are physiological antagonists in the inflammation process. Here we show that in mice and humans there is a spliced variant of p65, named p65 iso5, which binds the corticosteroid hormone dexamethasone amplifying the effect of the glucocorti…

Sleep disturbances and dysautonomic dysfunction are associated in patients with Parkinson’s disease

Insidious onset of Pisa syndrome after rasagiline therapy in a patient with Parkinson’s disease

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EFFECT OF A MULTIDISCIPLINARY ALS CLINIC ON NIV TOLERANCE AND SURVIVAL IN PATIENTS WITH AMYOTROPHIC LATERAL SCLEROSIS AND BULBAR IMPAIRMENT: A PROSPECTIVE STUDY

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Transcranial direct current stimulation for treatment of freezing of gait: A cross-over study

Background and objective Progression of Parkinson's disease (PD) is frequently characterized by the occurrence of freezing of gait (FOG) representing a disabling motor complication. We aim to investigate safety and efficacy of transcranial direct current stimulation of the primary motor cortex of PD patients with FOG. Methods In this cross-over, double-blind, sham-controlled study, 10 PD patients with FOG persisting in “on” state underwent anodal and sham direct current stimulation for 5 consecutive days. Clinical assessment over a 1-month period was performed. Results A significant improvement of gait, as assessed by the Stand Walk Sit test, with reduction in number and duration of FOG epi…

DIABETIC THORACIC POLYRADICULOPATHY: A CASE WITH CLINICAL IMPROVEMENT FROM INTRAVENOUS IMMUNOGLOBULIN.

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URIC ACID LEVELS IN SERUM AND CSF OF ALS PATIENTS

Objective: Urate (UA) is a potent antioxidant that effectively scavenges reactive nitrogen and oxygen radicals, and persons with a high plasma UA level may be at lower risk of some neurodegenerative disorders, as Parkinson’s disease (PD). Low plasma UA level has been observed in Alzheimer’s disease (AD) and vascular dementia, but there is no data on correlations to neuropsychological test results in these patient groups. Amyotrophic Lateral Sclerosis (ALS) is a devastating motor neuron disease, with a highly variable rate of progression and whose diagnosis is chiefly based on clinical and neurophysiological parameters. The etiopathogenesis is unknown, but the oxidative stress seems to play …

Frequency and determinants for hemorrhagic transformation of posterior cerebral stroke : Posterior ischemic stroke and hemorrhagic transformation.

BACKGROUND: hemorrhagic transformation is a threatening ischemic stroke complication. Frequency of hemorrhagic transformation differs greatly among studies, and its risk factors have been usually studied in patients with anterior ischemic stroke who received thrombolytic therapy. We evaluated, in a hospital-based series of patients with posterior ischemic stroke not treated with thrombolysis, frequency and risk factors of hemorrhagic transformation. Patients with posterior circulation stroke were seen in our Department during the period January 2004 to December 2009. Demographic and clinical information were collected. We estimated risk for spontaneous hemorrhagic transformation by means of…

Cyclical changes of cortical excitability and metaplasticity in migraine: evidence from a repetitive transcranial magnetic stimulation study.

The primary brain dysfunctions leading to the onset of a migraine attack remain largely unknown. Other important open questions concern the mechanisms of initiation, continuation, and termination of migraine pain, and the changes in brain function underlying migraine transformation. Brief trains of high-frequency repetitive transcranial magnetic stimulation (rTMS), when applied to the primary motor cortex at suprathreshold intensity (⩾120% of resting motor threshold [RMT]), elicit in healthy subjects a progressive, glutamate-dependent facilitation of the motor evoked potentials (MEP). Conversely, in conditions of increased cortical excitability, the rTMS trains induce inhibitory MEP respons…

ANODAL TRANSCRANIAL DIRECT CURRENT STIMULATION (TDCS) APPLIED TO THE MOTOR CORTEX AMELIORATES FREEZING OF GAIT IN PATIENTS AFFECTED BY PARKINSON’S DISEASE

Background: Progression of Parkinson’s disease (PD) is frequently characterized by the occurrence of freezing of gait (FOG), which generally does not improve with dopaminergic therapy and with current available surgical therapies. Recent evidences show that motor symptoms may be ameliorated by means of non-invasive brain stimulation techiniques in PD (transcranial current direct stimulation, TDCS; repetitive transcranial magnetic stimulation, RTMS). Objective: To investigate the efficacy of anodal TDCS in the treatment of FOG in PD. Excitatory anodal tDCS was applied unilaterally to the motor and premotor cortices controlateral to the most affected leg. Methods: randomized, double-blind, sh…

“Caratterizzazione funzionale di p65(-1), nuova isoforma di p65 del complesso NF-kB e preparazione di un clone per l'ingegnerizzazione di un topo p65(-1) -/-“

NF-kB è un fattore di trascrizione eucariotico e ubiquitario che regola l’espressione di geni coinvolti in molteplici processi cellulari come la risposta immunitaria, la flogosi, l’apoptosi, la crescita cellulare e lo sviluppo embrionale. Le proteine appartenenti alla famiglia di NF-kB sono p65, c-Rel, RelB, p50 e p52. Tali proteine svolgono la funzione di fattori trascrizionali legando specifiche consensus del DNA (consensus kB) sotto forma di omo - eterodimeri. Ogni membro della famiglia di NF-kB è caratterizzato dalla presenza di un dominio, altamente conservato, il “Rel Homology Domain” (RHD). Nel RHD sono stati mappati i sottodomini di dimerizzazione, interazione con gli inibitori (IkB…

In patient’s with Parkinson disease, autonomic symptoms are frequent and associated with other non-motor symptoms

Background: Autonomic symptoms and sleep disorders are common non-motor symptoms of Parkinson disease (PD), which are correlated with poor quality of life for patients. Purpose: To assess the frequency of autonomic symptoms in a consecutive series of PD patients and to correlate them with other motor and non-motor symptoms. Methods: All consecutive non-demented PD patients who underwent an extensive evaluation including Hoehn and Yahr staging, Unified Parkinson’s Disease Rating Scale, Beck’s Depression Inventory, Neuropsychiatric Inventory, PDQ-39 Scale, the Parkinson’s diseases Sleep Scale, the Epworth Sleepiness Scale and SCOPA-AUT scale were enrolled. Comorbidity has been also considered…

IMMUNOSUPPRESSANT TREATMENT AND CANCER RISK IN A COHORT OF PATIENTS AFFECTED BY MULTIPLE SCLEROSIS

Expression and developmental regulation of the cystine/glutamate exchanger (xc-) in the rat.

The cystine/glutamate exchanger (antiporter x c − ) is a membrane transporter involved in the uptake of cystine, the rate-limiting amino acid in the synthesis of glutathione. Recent studies suggest that the antiporter plays a role in the slow oxidative excitotoxity and in the pathological effects of β-N-oxalylamino-l-alanine, the molecule responsible for neurolathyrism, a neurotoxic upper motor neuron disease. The mouse cystine/glutamate exchanger has been cloned and showed to be composed of two distinct proteins, one of which being a novel protein, named xCT, of 502 amino acids and 12 putative trans-membrane domains. We have generated and purified a polyclonal antibody to mouse xCT and stu…

EXPRESSION OF THE CYSTINE/GLUTAMATE EXCHANGER IN THE RAT BRAIN

Reversible Pisa Syndrome in a patient with Parkinson's disease on rasagiline therapy

LATE MORTALITY OF HEMORRHAGIC TRANSFORMATION OF ISCHEMIC STROKE

Introduction. Hemorrhagic transformation (HT), a complication of ischemic stroke (IS) is supposed to influence patient’s prognosis. Aim of our study was to evaluate, in a hospital-based series of patients not treated with thrombolysis, the relationship between HT and late mortality. Methods. Mortality of individuals with spontaneous HT was compared to that of individuals without. Medical records of patients diagnosed with anterior IS during the period 2004-2006 were reviewed. Living status was obtained from the public record office of the municipality of Palermo or indirectly by telephone interview. Outcome measure was 90 days survival after IS onset. Kaplan-Meier estimates were used to con…

TRANSCRANIAL DIRECT CURRENT STIMULATION ENHANCES SUCKING OF A LIQUID BOLUS IN HEALTHY HUMANS

Abstract Background Transcranial direct current stimulation (tDCS) is a non-invasive technique used for modulating cortical excitability in vivo in humans. Here we evaluated the effect of tDCS on behavioral and electrophysiological aspects of physiological sucking and swallowing. Methods Twelve healthy subjects underwent three tDCS sessions (anodal, cathodal and sham stimulation) on separate days in a double-blind randomized order. The active electrode was placed over the right swallowing motor cortex. Repeated sucking and swallowing acts were performed at baseline and at 15 and 60 min after each tDCS session and the mean liquid bolus volume ingested at each time point was measured. We also…

CLINICAL EFFECTS OF DIFFERENT MONTAGES OF TRANSCRANIAL DIRECT CURRENT STIMULATION IN PATIENTS WITH PARKINSON’DISEASE

Positive ice pack test in a case of food-borne botulism: a clinical note

Urological dysfunctions in patients with Parkinson’s disease: clues from clinical and non-invasive urological assessment

Abstract Background Autonomic nervous system dysfunction, common in patients with Parkinson’s disease (PD), causes significant morbidity and it is correlated with poor quality of life. To assess frequency of urinary symptoms in patients with PD, without conditions known to interfere with urinary function. Methods Non-demented PD patients were consecutively enrolled from the outpatients clinic of our department. Scales investigating motor and non-motor symptoms were carried out. Evaluation of urinary dysfunctions was carried out using the AUTonomic Scale for Outcomes in Parkinson’s disease (SCOPA-AUT) questionnaire. Patients underwent noninvasive urological studies (nUS), including uroflowme…

Pisa syndrome after rasagiline therapy in a patient with Parkinson’s disease

Dear Editor, We have read with interest comments by Solla et al. [1] regarding our Letter to the Editor published in NeurologicalSciences titled ‘‘Insidious onset of Pisa Syndrome afterrasagiline therapy in a patient with Parkinson’s Disease’’[2]. We thank the authors for their interest in our paper, but we think it is necessary to make some clarifications regarding the temporal relationship between the onset of Pisa Syndrome (PS) and rasagiline therapy. PS occurred in fact after and not before rasagiline treatment as stated by Solla et al. In particular, PS occurred after a time interval of 6–12 months and anyway after rasagiline was added to patient’s therapy. This long time interval is o…

ESPRESSIONE DELL’ANTIPORTER CISTINA/GLUTAMMATO XC- NEL SISTEMA NERVOSO DI RATTO

Elevated cerebrospinal fluid and plasma homocysteine levels in ALS

Background:  High cerebrospinal fluid (CSF) and plasma levels of homocysteine (HC) have been reported in certain neurodegenerative disorders, such as Alzheimer’s, Parkinson’s diseases and, recently, amyotrophic lateral sclerosis (ALS). Objectives:  To assay the CSF and plasma levels of HC in ALS patients and controls, and to evaluate the relationship between HC levels and clinical variables of the disease. Methods:  Cerebrospinal fluid from sixty-nine (M/F 1.87) and plasma from sixty-five ALS patients (M/F 1.83) were taken and stored at −80°C until use. Controls (CSF = 55; plasma = 67) were patients admitted to our hospital for neurological disorders with no known relationship to HC changes…

IDENTIFICATION OF A NOVEL COMPOUND HETEROZYGOUS MUTATION OF SPG11 IN A PATIENT AFFECTED BY HSPWITH THIN CORPUS CALLOSUM

DYSAUTONOMIC DYSFUNCTION IN PARKINSON’DISEASE BY SCOPA-AUT SCALE

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PARKINSON’S DISEASE AND PARKINSON’S DISEASE FAMILIAL HISTORY. RESULTS OF A CASE-CONTROL STUDY

The importance of the reproducibility of oropharyngeal swallowing in amyotrophic lateral sclerosis. An electrophysiological study

Abstract Objective To investigate electrophysiologically the reproducibility of oropharyngeal swallowing in patients with ALS. Methods We enrolled 26 ALS patients, both with and without clinical signs of dysphagia, and 30 age-matched controls. The reproducibility of the electrophysiological signals related to the oral phase (electromyographic activity of the submental/suprahyoid muscles) and the pharyngeal phase (laryngeal-pharyngeal mechanogram) of swallowing across repeated swallows was assessed. To do this we computed two similarity indexes (SI) by using previously described mathematical algorithms. Results The reproducibility of oropharyngeal swallowing was significantly reduced both in…

Preliminary experience with a transcranial magnetic resonance-guided focused ultrasound surgery system integrated with a 1.5-T MRI unit in a series of patients with essential tremor and Parkinson's disease.

OBJECTIVETranscranial magnetic resonance–guided focused ultrasound surgery (tcMRgFUS) is one of the emerging noninvasive technologies for the treatment of neurological disorders such as essential tremor (ET), idiopathic asymmetrical tremor-dominant Parkinson’s disease (PD), and neuropathic pain. In this clinical series the authors present the preliminary results achieved with the world’s first tcMRgFUS system integrated with a 1.5-T MRI unit.METHODSThe authors describe the results of tcMRgFUS in a sample of patients with ET and with PD who underwent the procedure during the period from January 2015 to September 2017. A monolateral ventralis intermedius nucleus (VIM) thalamic ablation was pe…

A two-stage genome-wide association study of sporadic amyotrophic lateral sclerosis

The cause of sporadic amyotrophic lateral sclerosis (ALS) is largely unknown, but genetic factors are thought to play a significant role in determining susceptibility to motor neuron degeneration. To identify genetic variants altering risk of ALS, we undertook a two-stage genome-wide association study (GWAS): we followed our initial GWAS of 545 066 SNPs in 553 individuals with ALS and 2338 controls by testing the 7600 most associated SNPs from the first stage in three independent cohorts consisting of 2160 cases and 3008 controls. None of the SNPs selected for replication exceeded the Bonferroni threshold for significance. The two most significantly associated SNPs, rs2708909 and rs2708851 …

Cerebrospinal fluid tau protein is not a biological marker in amyotrophic lateral sclerosis.

Background:  Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder leading to progressive motor neuron cell death. Etiopathogenesis is still imperfectly known and much effort have been undertaken to find a biological marker that could help in the early diagnosis and in the monitoring of disease progression. Cerebrospinal fluid (CSF) concentrations of tau, an axonal microtubule-associated protein, have been measured in ALS with levels found increased in some studies and unchanged in others. Methods:  Total CSF tau level was assayed in a population of ALS patients (n = 57) and controls (n = 110) using a specific ELISA method. Results:  No significant differences in the median CS…

Frequency of cognitive impairment and factors associated in outpatients with Parkinson’s disease

LEPROSY: A CASE REPORT FROM SICILY, ITALY

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Is trans-cranial MR-guided Focused UltraSound a repeatable treatment option? Report of a successfully re-treated patient

Background: In recent years, transcranial Magnetic Resonance-guided Focused UltraSounds (tcMRgFUS) treatments for functional neurological disorders are giving a new thrust to the field of therapeutic brain lesioning. This technique has been proven safe and effective in selected patients. Here we present the case of a patient affected by tremor combined with parkinsonism who underwent a second tcMRgFUS thalamotomy because of relapsing tremor after a few months from the first tcMRgFUS treatment. Materials and Methods: A 72-year-old, right-handed man, who came to our observation because of a disabling tremor affecting mainly his upper right limb and refusing any invasive surgical procedure. Hi…

RISK FACTORS FOR DYSKINESIAS IN PATIENTS WITH PARKINSON'S DISEASE

Effects of More-Affected vs. Less-Affected Motor Cortex tDCS in Parkinson’s Disease

Objective. To evaluate therapeutic potential of different montages of transcranial direct current stimulation (tDCS) in Parkinson’s Disease (PD) patients with asymmetric motor symptoms. Materials and Methods. Fourteen patients with asymmetric PD underwent, while on treatment, seven separate sessions including electrophysiological and clinical evaluation at baseline and after anodal, cathodal and sham tDCS of the primary motor cortex (M1) of the two hemispheres. Changes in motor cortical excitability were evaluated by transcranial magnetic stimulation. Effects on motor symptoms were assessed by testing finger tapping and upper limb bradykinesia, and by using the Italian validated Movement Di…

Repeated courses of granulocyte colony-stimulating factor in amyotrophic lateral sclerosis: clinical and biological results from a prospective multicenter study

Granulocyte colony-stimulating factor (G-CSF) induces a transient mobilization of hematopoietic progenitor cells from bone marrow to peripheral blood. Our aim was to evaluate safety of repeated courses of G-CSF in patients with amyotrophic lateral sclerosis (ALS), assessing disease progression and changes in chemokine and cytokine levels in serum and cerebrospinal fluid (CSF). Twenty-four ALS patients entered an open-label, multicenter trial in which four courses of G-CSF and mannitol were administered at 3-month intervals. Levels of G-CSF were increased after treatment in the serum and CSF. Few and transitory adverse events were observed. No significant reduction of the mean monthly decrea…

A cervical myelopathy with a Hirayama disease-like phenotype

A 21-year-old man with a muscular atrophy of the left distal upper extremity is presented. The disorder had been progressive over a few years, showing an exacerbation of the hand's weakness when the patient worked in a chilled environment (i.e., in a cold room). The patient's diagnostic work-up was extensive and the MRI documented the presence of a cervical myelopathy, associated to an inversion of the physiological lordosis at the C5-C6 level, with a phenotype highly resembling Hirayama disease. This case indirectly supports the debated hypothesis that juvenile amyotrophy of the upper limb (Hirayama disease) is actually a type of cervical myelopathy, with a likely ischaemic pathogenesis of…

Frequency and determinants for hemorrhagic transformation of posterior cerebral stroke

Abstract Background hemorrhagic transformation is a threatening ischemic stroke complication. Frequency of hemorrhagic transformation differs greatly among studies, and its risk factors have been usually studied in patients with anterior ischemic stroke who received thrombolytic therapy. We evaluated, in a hospital-based series of patients with posterior ischemic stroke not treated with thrombolysis, frequency and risk factors of hemorrhagic transformation. Patients with posterior circulation stroke were seen in our Department during the period January 2004 to December 2009. Demographic and clinical information were collected. We estimated risk for spontaneous hemorrhagic transformation by …

DYSAUTOMIC DISFUNCTON OCCURS EARLY IN PARKINSON DISEASE

CSF HOMOCYSTEINE LEVELS IN AMYOTROPHC LATERAL SCLEROSIS

CSF homocysteine levels in Amyotrophic Lateral Sclerosis

Early and late mortality of spontaneous hemorrhagic transformation of ischemic stroke.

Background Hemorrhagic transformation (HT), a complication of ischemic stroke (IS), might influence patient's prognosis. Our aim is to evaluate, in a hospital-based series of patients not treated with thrombolysis, the relationship between HT and mortality. Methods We compared mortality of individuals with spontaneous HT with that of individuals without. Medical records of patients diagnosed with anterior IS were retrospectively reviewed. Outcome measures were 30- and 90-day survival after IS onset. Kaplan–Meier estimates were used to construct survival curves. Cox proportional hazards model was used to estimate hazard ratio (HR) for the main outcome measure (death). HT was stratified in he…

SERUM CREATINE KINASE LEVEL IN AMYOTROPHIC LATERAL SCLEROSIS: A USEFUL DIAGNOSTIC AID?

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