Sleep–wake problems in patients with amyotrophic lateral sclerosis: implications for patient management

SUMMARY Sleep–wake problems are frequent, although unrecognized, complications of amyotrophic lateral sclerosis (ALS). Sleep disorders such as insomnia, sleep-disordered breathing and restless legs syndrome have all been reported in patients with ALS, despite the limited number of studies and the small populations investigated so far. Sleep disturbances gradually worsen with disease progression, suggesting a relationship between the severity of disease and the neurodegenerative process. However, poor sleep can also be a consequence of several disturbances such as anxiety, depression, pain, choking, sialorrhea, fasciculations, cramps, nocturia and the inability to get comfortable and move f…

Effects of a Vibro-Tactile P300 Based Brain-Computer Interface on the Coma Recovery Scale-Revised in Patients With Disorders of Consciousness

Persons diagnosed with disorders of consciousness (DOC) typically suffer from motor and cognitive disabilities. Recent research has shown that non-invasive brain-computer interface (BCI) technology could help assess these patients’ cognitive functions and command following abilities. 20 DOC patients participated in the study and performed 10 vibro-tactile P300 BCI sessions over 10 days with 8–12 runs each day. Vibrotactile tactors were placed on the each patient’s left and right wrists and one foot. Patients were instructed, via earbuds, to concentrate and silently count vibrotactile pulses on either their left or right wrist that presented a target stimulus and to ignore …

A Human-Humanoid Interaction Through the Use of BCI for Locked-In ALS Patients Using Neuro-Biological Feedback Fusion.

This paper illustrates a new architecture for a human–humanoid interaction based on EEG-brain computer interface (EEG-BCI) for patients affected by locked-in syndrome caused by Amyotrophic Lateral Sclerosis (ALS). The proposed architecture is able to recognise users’ mental state accordingly to the biofeedback factor $\text {B}_{\text f}$ , based on users’ attention, intention, and focus, that is used to elicit a robot to perform customised behaviours. Experiments have been conducted with a population of eight subjects: four ALS patients in a near locked-in status with normal ocular movement and four healthy control subjects enrolled for age, education, and computer expertise. The results s…

Intraspinal stem cell transplantation for amyotrophic lateral sclerosis: Ready for efficacy clinical trials?

Intraspinal stem cell (SC) transplantation represents a new therapeutic approach for amyotrophic lateral sclerosis (ALS) clinical trials. There are considerable difficulties in designing future efficacy trials, some related to the field of ALS and some that are specific to SCs or the mode of delivery. In October 2015, the most controversial points on SC transplantation were addressed during an international workshop intended to bring together international SC and ALS researchers in a public discussion on a topic for which expertise is limited. During the meeting, a discussion was started on the basic structure of the ideal clinical trial testing the efficacy and safety of SC transplantation…

Complete locked-in and locked-in patients: Command following assessment and communication with vibro-tactile P300 and motor imagery brain-computer interface tools

Many patients with locked-in syndrome (LIS) or complete locked-in syndrome (CLIS) also need brain-computer interface (BCI) platforms that do not rely on visual stimuli and are easy to use. We investigate command following and communication functions of mindBEAGLE with 9 LIS, 3 CLIS patients and three healthy controls. This tests were done with vibro-tactile stimulation with 2 or 3 stimulators (VT2 and VT3 mode) and with motor imagery (MI) paradigms. In VT2 the stimulators are fixed on the left and right wrist and the participant has the task to count the stimuli on the target hand in order to elicit a P300 response. In VT3 mode an additional stimulator is placed as a distractor on the shoul…

THORACIC SYRINGOMYELIA IN A PATIENT WITH AMYOTROPHIC LATERAL SCLEROSIS

We report a patient with bulba r - onset, clinically defined, sporadic amyotrophic lateral sclerosis bearing an isolated syringomyelia of the lower thoracic portion of the spinal cord. This is a very unusual association between two rare and progressive disorders, both affecting the spinal motoneurons. Syringomyelia might have acted as a phenotypic modifier in this ALS patient.

Editorial: Breakthrough BCI Applications in Medicine

Reversible radiculomyelitis after ChAdOx1 nCoV-19 vaccination

Adverse events occurring after SARS-CoV-2 vaccination have been reported and are the subject of ongoing research. We present the case of a young woman with fully reversible radiculomyelitis, which happened after the first dose of the ChAdOx1 nCOVID-19 vaccine. A previously healthy woman in her 20s presented with a subacute onset of legs’ weakness and sensory disturbances, urinary dysfunction and cramping pain after receiving the first dose of the ChAdOx1 nCoV-19 vaccine. A diagnostic workup led to the diagnosis of inflammatory radiculomyelitis. Her clinical status improved, with complete recovery after a few months. The case described a reversible radiculomyelitis associated with the ChAdOx…

Performance Differences Using a Vibro-Tactile P300 BCI in LIS-Patients Diagnosed With Stroke and ALS

Plasma cortisol levels in amyotrophic lateral sclerosis

VARIABILI GENETICHE, BIOLOGICHE E CLINICHE COME FATTORI PROGNOSTICI DI PROGRESSIONE E SOPRAVVIVENZA NELLA SCLEROSI LATERALE AMIOTROFICA

Questo studio ha riguardato l'analisi di alcune variabili prognostiche e di sopravvivenza nella sclerosi laterale amiotrofica, con particolare riferimento alla caratterizzazione di nuovi geni ed al ruolo di interventi di management.

A novel compound heterozygous mutation in GALC associated with adult-onset Krabbe disease: case report and literature review

Krabbe disease (KD) is a rare autosomal recessive lipid storage leukodystrophy. It is caused by deficient enzyme activity resulting from mutations of the β-galactocerebrosidase (GALC) gene. KD is distinguished into subtypes based on the age of onset; these are early infantile, late infantile, juvenile, and adult-onset. We report a case of a 47-year-old Caucasian man with a 2-year history of muscle atrophy and weakness in both hands associated with pyramidal signs and mild spasticity in the lower limbs. An extensive work-up led this motor neuron disease-like disorder to be diagnosed as adult-onset KD. The patient was found to be compound heterozygous for two GALC mutations (p.G286D and p.Y49…

Performance Differences Using a Vibro-Tactile P300 BCI in LIS-Patients Diagnosed With Stroke and ALS

Patients with locked-in syndrome (LIS) are typically unable to move or communicate and can be misdiagnosed as patients with disorders of consciousness (DOC). Behavioral assessment scales are limited in their ability to detect signs of consciousness in this population. Recent research has shown that brain-computer interface (BCI) technology could supplement behavioral scales and allows to establish communication with these severely disabled patients. In this study, we compared the vibro-tactile P300 based BCI performance in two groups of patients with LIS of different etiologies: stroke (n = 6) and amyotrophic lateral sclerosis (ALS) (n = 9). Two vibro-tactile paradigms were administered to …

ALS-Related Mutant FUS Protein Is Mislocalized to Cytoplasm and Is Recruited into Stress Granules of Fibroblasts from Asymptomatic <b><i>FUS </i></b>P525L Mutation Carriers

<b><i>Background:</i></b> Amyotrophic lateral sclerosis (ALS) shows a strong genetic basis, with <i>SOD1</i>, <i>FUS</i>, <i>TARDBP</i>, and <i>C9ORF72 </i>being the genes most frequently involved<i>. </i>This has allowed identification of asymptomatic mutation carriers, which may be of help in understanding the molecular changes preceding disease onset. <b><i>Objectives:</i></b> We studied the cellular expression of FUS protein and the effect of heat-shock- and dithiothreitol-induced stress in fibroblasts from <i>FUS</i> P525L mutation carriers, healthy controls, and pati…

Reaching and Grasping a Glass of Water by Locked-In ALS Patients through a BCI-Controlled Humanoid Robot

Locked-in Amyotrophic Lateral Sclerosis (ALS) patients are fully dependent on caregivers for any daily need. At this stage, basic communication and environmental control may not be possible even with commonly used augmentative and alternative communication devices. Brain Computer Interface (BCI) technology allows users to modulate brain activity for communication and control of machines and devices, without requiring a motor control. In the last several years, numerous articles have described how persons with ALS could effectively use BCIs for different goals, usually spelling. In the present study, locked-in ALS patients used a BCI system to directly control the humanoid robot NAO (Aldebar…

Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

© 2018 Elsevier Inc.

THE COGNITIVE AND BEHAVIOURAL IMPAIRMENT IN AMYOTROPHIC LATERAL SCLEROSIS

Early and rapidly progressing respiratory failure in a patient with amyotrophic lateral sclerosis: when FVC% is misleading

Introduction Respiratory failure is the leading cause of death in amyotrophic lateral sclerosis (ALS) [1]. The involvement of respiratory function is a negative predictor of survival, which can be in part overcome by a prompt initiation of non-invasive mechanical ventilation (NIV). Seated forced vital capacity (FVC%) is a widely used measure to monitor respiratory function, and it is often taken as a surrogate outcome measure in clinical trials. However, it may be within a normal range in ALS patients with respiratory dysfunction [2]. Here we report on a case of an ALS patient with a rapidly evolving respiratory insufficiency, despite a rather normal FVC%. Case presentation The patient, a 6…

Preserved somatosensory discrimination predicts consciousness recovery in unresponsive wakefulness syndrome

Objective: To assess somatosensory discrimination and command following using a vibrotactile P300-based Brain-Computer Interface (BCI) in Unresponsive Wakefulness Syndrome (UWS), and investigate the predictive role of this cognitive process on the clinical outcomes.Methods: Thirteen UWS patients and six healthy controls each participated in two experimental runs in which they were instructed to count vibrotactile stimuli delivered to the left or right wrist. A BCI determined each subject's task performance based on EEG measures. All of the patients were followed up six months after the BCI assessment, and correlations analysis between accuracy rates and clinical outcome were investigated.Re…

Prognostic Role of CSF β-amyloid 1–42/1–40 Ratio in Patients Affected by Amyotrophic Lateral Sclerosis

The involvement of β-amyloid (Aβ) in the pathogenesis of amyotrophic lateral sclerosis (ALS) has been widely discussed and its role in the disease is still a matter of debate. Aβ accumulates in the cortex and the anterior horn neurons of ALS patients and seems to affect their survival. To clarify the role of cerebrospinal fluid (CSF) Aβ 1–42 and Aβ 42/40 ratios as a potential prognostic biomarker for ALS, we performed a retrospective observational study on a cohort of ALS patients who underwent a lumbar puncture at the time of the diagnosis. CSF Aβ 1–40 and Aβ 1–42 ratios were detected by chemiluminescence immunoassay and their values were correlated with clinical features. We found a signi…

Percutaneous endoscopic gastrostomy in amyotrophic lateral sclerosis: effect on survival.

Abstract Background Percutaneous endoscopic gastrostomy (PEG) is offered to amyotrophic lateral sclerosis (ALS) patients with severe dysphagia. Immediate benefits of PEG are adequate food intake and weight stabilization. However, the impact of PEG on survival is still uncertain. In this work we retrospectively evaluated the effect of PEG on survival in a cohort of ALS patients followed in a tertiary referral centre. Methods Between 2000 and 2007, 150 dysphagic ALS patients were followed until death or tracheostomy. PEG was placed in 76 patients who accepted the procedure and survival was analysed using the Kaplan–Meier life-table method. Results In ALS patients submitted to PEG, no major co…

Autosomal dominant Brown–Vialetto–Van Laere syndrome with UBQLN1 mutation

Sleep-wake disturbances in patients with amyotrophic lateral sclerosis

Objective To evaluate the frequency, severity and determinants of sleep disturbances in patients with amyotrophic lateral sclerosis (ALS). Methods Information about night-time complaints was collected using a standardised questionnaire, the Pittsburgh Sleep Quality Index (PSQI), and the Epworth Sleepiness Scale (ESS) in a group of 100 patients with ALS and in 100 control subjects matched for age and sex. Functional disability was assessed using the ALS Functional Rating Scale-Revised (ALSFRS-R). Sleep was studied by overnight polysomnography in 12 patients. Results Fifty-nine patients with ALS and 36 controls reported sleep disturbances. The mean global PSQI score of patients with ALS was s…

Unilateral laryngeal and hypoglossal paralysis (Tapia's syndrome) in a patient with an inflammatory pseudotumor of the neck

Tapia’s syndrome (TS) is a rare condition thought tobe causedby njury to the extracranial course of both recurrent laryngeal branch f the vagal nerve and hypoglossal nerve. First described in 1904, t occurs with unilateral paralysis of the vocal cord and tongue, ith normal function of the soft palate. Commonly reported causes re direct trauma, neurofibromatosis of X and XII nerves, carotid rtery dissection involving the ascending pharyngeal artery, and isplacement of endotracheal tube during general anesthesia [1].

PERCUTANEOUS ENDOSCOPIC GASTROSTOMY (PEG) IMPROVES SURVIVAL IN AMYOTROPHIC LATERAL SCLEROSIS

Causes and place of death in Italian patients with amyotrophic lateral sclerosis

Objectives - To determine the causes and place of death in a cohort of Italian patients with amyotrophic lateral sclerosis (ALS). A better understanding of the likely causes of death in ALS might improve the palliative care at the end-of-life, whereas knowing the place of death will help to verify the need for highly specialized care services, e.g. hospice and nursing home. Patients and methods - Between 2000 and 2008, 182 ALS patients (onset: spinal, 127; bulbar, 55; M/F: 1.6) were followed in a single ALS Tertiary Centre in Palermo, Sicily, Italy until death. Medical data for each individual patient were recorded in a large database throughout the disease course. Information concerning ca…

Genetic investigation of amyotrophic lateral sclerosis patients in south Italy: a two-decade analysis

Amyotrophic lateral sclerosis (ALS) is a multifactorial disease characterized by the interplay of genetic and environmental factors. In the majority of cases, ALS is sporadic, whereas familial forms occur in less than 10% of patients. Herein, we present the results of molecular analyses performed in a large cohort of Italian ALS patients, focusing on novel and already described variations in ALS-linked genes. Our analysis revealed that more than 10% of tested patients carried a mutation in one of the major ALS genes, with C9orf72 hexanucleotide expansion being the most common mutation. In addition, our study confirmed a significant association between ALS patients carrying the ATNX-1 interm…

Additional file 1: of Mutations in ATP13A2 (PARK9) are associated with an amyotrophic lateral sclerosis-like phenotype, implicating this locus in further phenotypic expansion

Figure S1. a Schematic of the endogenous zebrafish atp13a2 ortholog. The exons are shown are rectangles and the introns as horizontal lines. The splice junctions targeted with antisense morpholino oligonucleotides (atp13a2_3x4_SB and atp13a2_3x6_SB) are shown with red asterisks. b Gel images showing the efficiency of the atp13a2_3x4_SB and atp13a2_3x6_SB morpholinos. The first lane in each gel photograph shows amplicons from the respective loci flanking the targeted sequences, with no aberrations observed. In the embryos injected with morpholino oligonucleotides, aberrant bands were evident, showing that the morpholinos were efficient in knocking down the expression of endogenous atp13a2. F…

RESTLESS LEGS SYNDROME IN PATIENTS WITH AMYOTROPHIC LATERAL SCLEROSIS: A CASE-CONTROL STUDY.

Ethical issues: invasive ventilation in amyotrophic lateral sclerosis.

The first man was a school headmaster. By his eye-gaze system he is able to order coins to enlarge his 10-year collection. His grandchildren extort presents from him in exchange for help. The second was a prefect and even now insists that the flowers in the garden represent the national flag. In spite of his gastrostomy, he still likes to sip his espresso from porcelain cups. The ventilation circuit 24/7 has not changed his custom to read the newspapers and listen to classical music in the living room. That girl is a young mum. She is fed by a tube, but she always makes her little child laugh with the dialectal phrases that she writes on the screen. The surgeon, every day in his electric wh…

The Primitive Palmomental Reflex in Amyotrophic Lateral Sclerosis

<b><i>Background and Purpose:</i></b> The palmomental reflex (PMR) is a primitive reflex that might be released due to inhibition in adulthood. It has been associated with several neurodegenerative conditions. The aim of the present study was to evaluate the frequency of PMR in amyotrophic lateral sclerosis (ALS). <b><i>Patients and Methods:</i></b> Non-demented ALS patients (<i>n</i> = 179) were recruited. Two groups of disease controls were enrolled: (a) non-demented patients with other neurological disorders (NC;<i> n</i> = 86, mean age 60 ± 14 years); (b) healthy subjects, healthy controls (HC; <i>n</i> …

Genomic portrait of a sporadic amyotrophic lateral sclerosis case in a large spinocerebellar ataxia type 1 family

Background: Repeat expansions in the spinocerebellar ataxia type 1 (SCA1) gene ATXN1 increases the risk for amyotrophic lateral sclerosis (ALS), supporting a relationship between these disorders. We recently reported the co-existence, in a large SCA1 family, of a clinically definite ALS individual bearing an intermediate ATXN1 expansion and SCA1 patients with a full expansion, some of which manifested signs of lower motor neuron involvement. Methods: In this study, we employed a systems biology approach that integrated multiple genomic analyses of the ALS patient and some SCA1 family members. Results: Our analysis identified common and distinctive candidate genes/variants and related biolog…

HFE p.H63D polymorphism does not influence ALS phenotype and survival.

It has been recently reported that the p.His63Asp polymorphism of the HFE gene accelerates disease progression both in the SOD1 transgenic mouse and in amyotrophic lateral sclerosis (ALS) patients. We have evaluated the effect of HFE p.His63Asp polymorphism on the phenotype in 1351 Italian ALS patients (232 of Sardinian ancestry). Patients were genotyped for the HFE p.His63Asp polymorphism (CC, GC, and GG). All patients were also assessed for C9ORF72, TARDBP, SOD1, and FUS mutations. Of the 1351 ALS patients, 363 (29.2%) were heterozygous (GC) for the p.His63Asp polymorphism and 30 (2.2%) were homozygous for the minor allele (GG). Patients with CC, GC, and GG polymorphisms did not significa…

Prevalenza di Osteoporosi e Osteopenia in una popolazione adulto-anziana: Zabut Aging Project

Assessing Command-Following and Communication With Vibro-Tactile P300 Brain-Computer Interface Tools in Patients With Unresponsive Wakefulness Syndrome

Persons diagnosed with disorders of consciousness (DOC) typically suffer from motor disablities, and thus assessing their spared cognitive abilities can be difficult. Recent research from several groups has shown that non-invasive brain-computer interface (BCI) technology can provide assessments of these patients' cognitive function that can supplement information provided through conventional behavioral assessment methods. In rare cases, BCIs may provide a binary communication mechanism. Here, we present results from a vibrotactile BCI assessment aiming at detecting command-following and communication in 12 unresponsive wakefulness syndrome (UWS) patients. Two different paradigms were admi…

MARITAL STATUS IS A PROGNOSTIC FACTOR IN AMYOTROPHIC LATERAL SCLEROSIS

Background and objectives Several variables have been linked to a shorter survival in patients with amyotrophic lateral sclerosis (ALS), for example, female sex, older age, site of disease onset, rapid disease progression, and a relatively short diagnostic delay. With regard to marital status, previous studies suggested that living with a partner might be associated to a longer survival and a higher likelihood to proceed to tracheostomy. Therefore, to further strengthen this hypothesis, we investigated the role of marital status as a prognostic variable in a cohort of ALS patients. Methods We performed a retrospective analysis on 501 consecutive ALS patients for which a complete disease's n…

A rapidly progressive motor neuron disease associated to a natural killer cells leukaemia

une system play a complex role, either protective or toxic, in ALS pathogenesis [1–3]. In particular, compelling evidence indicate that increased blood level of natural killer (NK) and NK-T cells may contribute to the disease development and progression [2,3]. Here, we report on a patient with an aggressive Motor Neuron Disease (MND) associated with NK/NK-T cells leukaemia. 1. Case report A 79-year-old man presented with several months-history of a progressive atrophy and weakness of the upper limbs, which quickly spread to the lower limbs. Onset was subtle and apparently occurred in the month of July (the specific date is not shown for privacy), when the patient noticed a mild weakness in …

Paraneoplastic motor neuron disease associated with breast cancer.

Bilateral Iatrogenic Femoral Neuropathy

Dear Editor, Postoperative femoral neuropathy is an uncommon complication associated with pelvic/abdominal surgery. The main mechanism underlying this neuropathy is stretching and/or prolonged compression of the nerve.1,2 The nerve compression can be caused by the self-retaining retractors that are sometimes used during surgery directly constricting the nerve against the pelvic sidewall and inducing ischemia.1 Symptoms of femoral neuropathy are weakness of ipsilateral hip flexion and knee extension, and sensory deficit on the anteromedial thigh. The prognosis is generally good, with partial or complete recovery being common. Postoperative femoral neuropathy is generally unilateral2,3,4; bil…

Reaching and grasping a glass of water by locked-in ALS patients through a BCI-controlled humanoid robot

Tracheostomy mechanical ventilation in patients with amyotrophic lateral sclerosis: Clinical features and survival analysis

article i nfo Background: Tracheostomy mechanical ventilation (TMV) is performed in amyotrophic lateral sclerosis (ALS) patients with a respiratory failure or when the non-invasive ventilation (NIV) is no longer effective. We evaluated the clinical characteristics and survival of a cohort of tracheostomized ALS patients, followed in a single ALS Clinical Center. Methods: Between 2001 and 2010, 87 out of 279 ALS patients were submitted to TMV. Onset was spinal in 62 and bulbar in 25. After tracheostomy, most patients were followed up through telephone interviews to caregivers. A complete survival analysis could be performed in fifty-two TMV patients. Results: 31.3% ALS patients underwent tra…

PETECHIAL BRAIN HAEMORRHAGES IN ACUTE LYMPHOBLASTIC LEUKAEMIA.

A 37-year-old office worker was referred to our hospital with severe weakness, malaise, headache and altered mental status. He was mildly febrile (37.5°C) with reported episodes of agitation. A blood count revealed 709 720 white blood cells (WBC) / μl with 33 000 platelets/μl. The clinical, imaging and laboratory workup led to a diagnosis of acute lymphoblastic leukaemia (ALL) …

Causes and place of death in Italian patients with amyotrophic lateral sclerosis

Objectives - To determine the causes and place of death in a cohort of Italian patients with amyotrophic lateral sclerosis (ALS). A better understanding of the likely causes of death in ALS might improve the palliative care at the end-of-life, whereas knowing the place of death will help to verify the need for highly specialized care services, e.g. hospice and nursing home. Patients and methods - Between 2000 and 2008, 182 ALS patients (onset: spinal, 127; bulbar, 55; M/F: 1.6) were followed in a single ALS Tertiary Centre in Palermo, Sicily, Italy until death. Medical data for each individual patient were recorded in a large database throughout the disease course. Information concerning ca…

Mutations in ATP13A2 (PARK9) are associated with an amyotrophic lateral sclerosis-like phenotype, implicating this locus in further phenotypic expansion

Background Amyotrophic lateral sclerosis [1] is a genetically heterogeneous neurodegenerative disorder, characterized by late-onset degeneration of motor neurons leading to progressive limb and bulbar weakness, as well as of the respiratory muscles, which is the primary cause of disease fatality. To date, over 25 genes have been implicated as causative in ALS with C9orf72, SOD1, FUS, and TARDBP accounting for the majority of genetically positive cases. Results We identified two patients of Italian and French ancestry with a clinical diagnosis of juvenile-onset ALS who were mutation-negative in any of the known ALS causative genes. Starting with the index case, a consanguineous family of Ita…

The capacity to consent to treatment in amyotrophic lateral sclerosis: a preliminary report

Background: Facing the relentless worsening of their condition, ALS patients are required to make decisions on treatments and end-of-life care. A cognitive impairment showed to be a negative prognostic factor in ALS patients, perhaps affecting the ability to make informed decisions. Notwithstanding its crucial role, the capacity to consent to treatment (CCT) has never been evaluated in these patients. Objectives: To assess the CCT in an ALS cohort in comparison to a control group, and to study the effects of demographic and clinical variables on this high-level cognitive function. Methods: 102 ALS patients and 106 healthy controls (HC) were enrolled. CCT was assessed using the MacArthur Com…

Tracheostomy mechanical ventilation in amyotrophic lateral sclerosis.

A novel S379A TARDBP mutation associated to late-onset sporadic ALS

Since 2008, several groups have reported a lot of dominant mutations in TARDBP gene as a primary cause of Amyotrophic lateral sclerosis (ALS). Mutations in TARDBP gene are responsible for 4–5% of familial ALS (fALS) and nearly 1% of sporadic ALS (sALS). To date, over 50 dominant mutations were found in TDP-43 in both familial and sporadic ALS patients, most of which were missense mutations in the C-terminal glycine-rich region. Herein, we describe the clinical and genetic analysis of an Italian non-familial ALS patient with a late onset and a rapid disease progression, which led to the discovery of a novel TARDBP mutation. After neurological evaluation, molecular investigation highlighted t…

Percutaneous endoscopic gastrostomy in amyotrophic lateral sclerosis

Background: Percutaneous endoscopic gastrostomy (PEG) is offered to amyotrophic lateral sclerosis (ALS) patients with severe dysphagia. Immediate benefits of PEG are adequate food intake and weight stabilization. However, the impact of PEG on survival is still uncertain. In this work we retrospectively evaluated the effect of PEG on survival in a cohort of ALS patients followed in a tertiary referral centre. Methods: Between 2000 and 2007, 150 dysphagic ALS patients were followed until death or tracheostomy. PEG was placed in 76 patients who accepted the procedure and survival was analysed using the Kaplan-Meier life-table method. Results: In ALS patients submitted to PEG, no major complica…

FUS mutations in sporadic amyotrophic lateral sclerosis

Mutations in the FUS gene have recently been described as a cause of familial amyotrophic lateral sclerosis (ALS), but their role in the pathogenesis of sporadic ALS is unclear. We undertook mutational screening of all coding exons of FUS in 228 sporadic ALS cases, and, as previous reports suggest that exon 15 represents a mutational hotspot, we sequenced this exon in an additional 1295 sporadic cases. Six variants in six different cases were found, indicating that FUS mutations can underlie apparently sporadic ALS, but account for less than 1% of this form of disease. © 2010 .

Plasma cortisol level in amyotrophic lateral sclerosis

Background. Amyotrophic Lateral sclerosis (ALS) is associated with a significant distress, being linked to changes in hypothalamic-pituitary-adrenal axis activity. A loss of cortisol circadian rhythmicity in ALS patients was suggested, while more recently an increased plasma cortisol level in the disease has been reported. Objective. To assay the circadian plasma cortisol level in ALS and to study its relationship with the clinical phenotype and the rate of disease progression. Patients and methods. 135 ALS patients (Bulbar, 33; Spinal, 102; M/F = 1.73) and 110 controls (not affected by neurological or psychiatric disorders, free of drugs; M/F = 1.75) were recruited. Disease progression was…

Cognitive Impairment and Osteoporosis in persons 50+ years old: a population-based study.

FACTORS AFFECTING THE DIAGNOSTIC DELAY IN AMYOTROPHIC LATERAL SCLEROSIS

Abstract Background Although amyotrophic lateral sclerosis (ALS) is a relentlessly progressive disorder, early diagnosis allows a prompt start with the specific drug riluzole and an accurate palliative care planning. ALS at onset may however mimic several disorders, some of them treatable ( e.g. , multifocal motor neuropathy) or epidemiologically more frequent ( e.g. , cervical myelopathy). Objective To study the delay from onset to diagnosis in a cohort of ALS patients and to the variables that may affect it. Methods We performed a retrospective analysis of the diagnostic delays in a cohort of 260 patients affected by ALS (M/F = 1.32) followed at our tertiary referral ALS Center between 20…

CSF neurofilament proteins as diagnostic and prognostic biomarkers for amyotrophic lateral sclerosis

Elevated cerebrospinal fluid (CSF), Neurofilament Light (NF-L) and phosphorylated Heavy (pNF-H) chain levels have been found in Amyotrophic Lateral Sclerosis (ALS), with studies reporting a correlation of both neurofilaments (NFs) with the disease progression. Here, we measured NF-L and pNF-H concentrations in the CSF of ALS patients from a single tertiary Center and investigated their relationship with disease-related variables. A total of 190 ALS patients (Bulbar, 29.9%; Spinal, 70.1%; M/F = 1.53) and 130 controls with mixed neurological diseases were recruited. Demographic and clinical variables were recorded, and Delta FS was used to rate the disease progression. Controls were divided i…

Diabetic thoracic radiculopathy: a case of a young woman with clinical improvement following immunotherapy.

Thoracic radiculopathy is a rare cause of thoracic-abdominal or abdominal pain in subjects with poorly controlled diabetes. We present a case of a young woman with type I diabetes and a severe abdominal pain in both lower quadrants. An extensive diagnostic gastroenterological and gynaecological workup did not disclose abnormalities. Electromyography revealed an initial polyneuropathy and significant neurogenic abnormalities in the T10-T12 paravertebral muscles. Following the hypothesis that the radiculopathy-related abdominal pain might have an immuno-mediated pathogenesis, the patient underwent a complex trial of immunotherapy, which was accompanied by a sustained improvement over months t…

FUS MUTATIONS IN SPORADIC AMYOTROPHIC LATERAL SCLEROSIS: CLINICAL AND GENETIC ANALYSIS

Fused in sarcoma (FUS) or translocation in liposarcoma (TLS), a DNA/RNA-binding protein, causes a dominant autosomal inherited form of amyotrophic lateral sclerosis (ALS), ALS 6. Its main role in neurodegeneration is highlighted by the presence of cytoplasmic accumulation of its mutant protein form in ALS patients. To further define the frequency and spectrum of FUS gene mutations, we have performed a molecular screening of a cohort of 327 Italian patients from Southern Italy with sporadic ALS (SALS). We identified 4 patients carrying 3 different missense mutations and several polymorphisms. Two different substitutions occurring in the same amino acidic position have been observed in 2 pati…

Effects of Repeating a Tactile Brain-Computer Interface on Patients with Disorder of Consciousness: A Hint of Recovery?

Brain-computer interface (BCI) has been emerging as an assessment tool for patients with disorder of consciousness (DOC). With the advantages of high time resolution, low cost and portable design, EEG based BCI systems are especially suitable for bedside measurement. Recent studies showed the successful application of an EEG based BCI on DOC assessment and communication. However, the effect of repeated BCI measurement on this patient group is not clear. In this study, a tactile BCI paradigm was repeated 12 runs for 10 consecutive days on 5 DOC patients. Although the BCI performance varied among runs and days, every patient reached at least once the accuracy above 60%. Moreover, the Coma Rec…

Response to the letter to the Editor: Comments on marital status is a prognostic factor in amyotrophic lateral sclerosis. Safiri S et al

Tau protein as a diagnostic and prognostic biomarker in amyotrophic lateral sclerosis

BACKGROUND AND PURPOSE To test the hypothesis that total tau (tTau), tau phosphorylated at threonine 181 (pTau) and pTau/tTau ratio in the cerebrospinal fluid (CSF) are diagnostic and prognostic biomarkers of amyotrophic lateral sclerosis (ALS), we performed a retrospective observational study in a large cohort of ALS patients and controls. METHODS We enrolled 196 ALS patients and 91 controls, who included patients with ALS-mimicking diseases and those with non-neurodegenerative diseases. All patients underwent lumbar puncture for CSF analysis at the time of the diagnostic evaluation or to first referral. We measured tTau and pTau levels in the CSF by chemiluminescence enzyme immunoassay. R…

Incidence of amyotrophic lateral sclerosis in Sicily: A population based study

Our objective was to investigate incidence of amyotrophic lateral sclerosis (ALS) in Sicily, southern Italy, by means of a population based study. We included people with ALS resident in fi ve Sicilian provinces, whose onset occurred in the two-year period 2005 2006 (population at 31 December 2006: 3,481,096 inhabitants). A multisource case-fi nding procedure was adopted and patients were classifi ed as affected by ALS according to revised El Escorial criteria. During the two-year surveillance period, 97 patients meeting eligibility criteria included 57 males (58.8%) and 40 females (41.2%). Crude annual incidence rate was 1.4/100,000 person years (95% CI 1.33 1.47). The incidence rate was h…

Exome Sequencing Reveals VCP Mutations as a Cause of Familial ALS

Summary Using exome sequencing, we identified a p.R191Q amino acid change in the valosin-containing protein ( VCP ) gene in an Italian family with autosomal dominantly inherited amyotrophic lateral sclerosis (ALS). Mutations in VCP have previously been identified in families with Inclusion Body Myopathy, Paget disease, and Frontotemporal Dementia (IBMPFD). Screening of VCP in a cohort of 210 familial ALS cases and 78 autopsy-proven ALS cases identified four additional mutations including a p.R155H mutation in a pathologically proven case of ALS. VCP protein is essential for maturation of ubiquitin-containing autophagosomes, and mutant VCP toxicity is partially mediated through its effect on…

The role of ethical attitudes in the mortality of patients with disorders of consciousness.

Long-Lasting Cranial Nerve III Palsy as a Presenting Feature of Chronic Inflammatory Demyelinating Polyneuropathy

We describe a patient with chronic inflammatory demyelinating polyneuropathy (CIDP) in which an adduction deficit and ptosis in the left eye presented several years before the polyneuropathy. A 52-year-old man presented with a 14-year history of unremitting diplopia, adduction deficit, and ptosis in the left eye. At the age of 45 a mild bilateral foot drop and impaired sensation in the four limbs appeared, with these symptoms showing a progressive course. The diagnostic workup included EMG/ENG which demonstrated reduced conduction velocity with bilateral and symmetrical sensory and motor involvement. Cerebrospinal fluid studies revealed a cytoalbuminologic dissociation. A prolonged treatmen…

MindBEAGLE — A new system for the assessment and communication with patients with disorders of consciousness and complete locked-in syndrom

Patients with disorders of consciousness (DOC) cannot reply to questions or clinical assessments using voluntary motor control, and therefore it is very difficult to assess their cognitive capabilities and conscious awareness. Patients who are locked-in (LIS) are instead fully conscious, and they can communicate with their preserved eye movements. However, when the residual oculomotor activity is also lost (e.g., patients with amyotrophic lateral sclerosis disease of very long duration), the locked-in status becomes complete (CLIS). In CLIS patients, detection of conscious awareness may become very challenging, similarly to the subjects with DOC. mindBEAGLE has a physiological testing batte…

MTHFR C677T allelic variant is not associated to plasma and cerebrospinal fluid homocysteine in amyotrophic lateral sclerosis

Amiotrophic lateral sclerosis (ALS) is a neurological disorder with a multifactorial etiopathogenesis including excitotoxicity, intracellular calcium increase and mitochondrial damage together with oxidative stress and apoptosis. Overall, the relationship between homocysteine (Hcy), motoneuron death and ALS appears to be complex and still under investigation. It has been already shown that Hcy is elevated in plasma and cerebrospinal fluid (CSF) of ALS patients, although mechanisms of hyperhomocysteinemia have not been elucidated yet. MTHFR C677T variant is the most common genetic determinant of increased homocysteinemia, but no studies regarding the effect of this polymorphism in ALS patien…

Ataxin-1 and ataxin-2 intermediate-length PolyQ expansions in amyotrophic lateral sclerosis.

ABSTRACT Objective: Recent evidence suggests that intermediate-length polyglutamine (PolyQ) expansions in the ataxin-2 ( ATXN-2 ) gene are a risk factor for amyotrophic lateral sclerosis (ALS). This work was undertaken with the aim to investigate the frequency of ataxin-1 ( ATXN-1 ) and ATXN-2 PolyQ expansions in a cohort of patients with sporadic ALS (sALS) and patients with familial ALS (fALS) from southern Italy. Methods: We assessed the PolyQ lengths of ATXN-1 and ATXN-2 in 405 patients with sALS, 13 patients with fALS, and 296 unrelated controls without history of neurodegenerative disorders. Results: We found significantly higher intermediate PolyQ expansions ≥32 for ATXN-1 alleles an…

Risk factors for cognitive impairment in subjects with Behçet's disease

In the present study we evaluated the prevalence and risk factors for cognitive impairment in subjects with Behçet's Disease (BD). The following risk factors were studied: age, education, disease duration, activity of disease, prednisone dosage, and anxiety and depression levels. Twenty-six BD out-patients without overt neurological involvement and 26 sex-matched controls completed a comprehensive neuropsychological battery. Compared to controls, BD subjects were significantly impaired on tasks evaluating long-term verbal and nonverbal memory, and visuospatial skills. Cognitive impairment was evident in 46.1% of BD patients compared with none of control subjects (p<.0001), with memory repr…

How brain-computer interface technology may improve the diagnosis of the disorders of consciousness: A comparative study

ObjectiveClinical assessment of consciousness relies on behavioural assessments, which have several limitations. Hence, disorder of consciousness (DOC) patients are often misdiagnosed. In this work, we aimed to compare the repetitive assessment of consciousness performed with a clinical behavioural and a Brain-Computer Interface (BCI) approach.Materials and methodsFor 7 weeks, sixteen DOC patients participated in weekly evaluations using both the Coma Recovery Scale-Revised (CRS-R) and a vibrotactile P300 BCI paradigm. To use the BCI, patients had to perform an active mental task that required detecting specific stimuli while ignoring other stimuli. We analysed the reliability and the effic…

The eye-tracking computer device for communication in amyotrophic lateral sclerosis

Objective To explore the effectiveness of communication and the variables affecting the eye-tracking computer system (ETCS) utilization in patients with late-stage amyotrophic lateral sclerosis (ALS). Methods We performed a telephone survey on 30 patients with advanced non-demented ALS that were provisioned an ECTS device. Median age at interview was 55 years (IQR = 48–62), with a relatively high education (13 years, IQR = 8–13). A one-off interview was made and answers were later provided with the help of the caregiver. The interview included items about demographic and clinical variables affecting the daily ETCS utilization. Results The median time of ETCS device possession was 15 months …