Effects of a short period of postural training on postural stability and vestibulospinal reflexes.

The effects of postural training on postural stability and vestibulospinal reflexes (VSRs) were investigated in normal subjects. A period (23 minutes) of repeated episodes (n = 10, 50 seconds) of unipedal stance elicited a progressive reduction of the area covered by centre of pressure (CoP) displacement, of average CoP displacement along the X and Y axes and of CoP velocity observed in this challenging postural task. All these changes were correlated to each other with the only exception of those in X and Y CoP displacement. Moreover, they were larger in the subjects showing higher initial instability in unipedal stance, suggesting that they were triggered by the modulation of sensory afferents signalling body sway. No changes in bipedal stance occurred soon and 1 hour after this period of postural training, while a reduction of CoP displacement was apparent after 24 hours, possibly due to a beneficial effect of overnight sleep on postural learning. The same period of postural training also reduced the CoP displacement elicited by electrical vestibular stimulation (EVS) along the X axis up to 24 hours following the training end. No significant changes in postural parameters of bipedal stance and VSRs could be observed in control experiments where subjects were tested at identical time points without performing the postural training. Therefore, postural training led to a stricter control of CoP displacement, possibly acting through the cerebellum by enhancing feedforward mechanisms of postural stability and by depressing the VSR, the most important reflex mechanism involved in balance maintenance under challenging conditions.

Retrospective observational study on the use of acetyl-L-carnitine in ALS.

ALCAR (Acetyl-L-carnitine) is a donor of acetyl groups and increases the intracellular levels of carnitine, the primary transporter of fatty acids across the mitochondrial membranes. In vivo studies showed that ALCAR decrease oxidative stress markers and pro-inflammatory cytokines. In a previous double-blind placebo-controlled phase II trial showed positive effects on self-sufficiency (defined as a score of 3+ on the ALSFRS-R items for swallowing, cutting food and handling utensils, and walking) ALSFRS-R total score and FVC. We conducted an observational, retrospective, multicentre, case-control study to provide additional data on the effects of ALCAR in subjects with ALS in Italy. Subjects treated with ALCAR 1.5 g/day or 3 g/day were included and matched with not treated subjects by sex, age at diagnosis, site of onset, and time from diagnosis to baseline, (45 subjects per group). ALCAR 3 g/day vs not treated: 22 not treated subjects (48.9%) were still alive at 24 months after baseline, compared to 23 (51.1%) treated subjects (adj. OR 1.18, 95% CI 0.46-3.02). No statistically significant differences were detected in ALSFRS nor FVC nor self-sufficiency. ALCAR 1.5 g/day vs not treated: 22 not treated subjects (48.9%) were still alive at 24 months after baseline, compared to 32 (71.1%) treated subjects (adj. OR 0.27, 95% CI 0.10-0.71). For ALSFRS-R, a mean slope of - 1.0 was observed in treated subjects compared to - 1.4 in those not treated (p = 0.0575). No statistically significant difference was detected in the FVC nor self-sufficiency. Additional evidence should be provided to confirm the efficacy of the drug and provide a rationale for the dosage.

Blood Analytes as Biomarkers of Mechanisms Involved in Alzheimer's Disease Progression.

Alzheimer's disease (AD) is the leading cause of dementia, but the pathogenetic factors are not yet well known, and the relationships between brain and systemic biochemical derangements and disease onset and progression are unclear. We aim to focus on blood biomarkers for an accurate prognosis of the disease. We used a dataset characterized by longitudinal findings collected over the past 10 years from 90 AD patients. The dataset included 277 observations (both clinical and biochemical ones, encompassing blood analytes encompassing routine profiles for different organs, together with immunoinflammatory and oxidative markers). Subjects were grouped into four severity classes according to the Clinical Dementia Rating (CDR) Scale: mild (CDR = 0.5 and CDR = 1), moderate (CDR = 2), severe (CDR = 3) and very severe (CDR = 4 and CDR = 5). Statistical models were used for the identification of potential blood markers of AD progression. Moreover, we employed the Pathfinder tool of the Reactome database to investigate the biological pathways in which the analytes of interest could be involved. Statistical results reveal an inverse significant relation between four analytes (high-density cholesterol, total cholesterol, iron and ferritin) with AD severity. In addition, the Reactome database suggests that such analytes could be involved in pathways that are altered in AD progression. Indeed, the identified blood markers include molecules that reflect the heterogeneous pathogenetic mechanisms of AD. The combination of such blood analytes might be an early indicator of AD progression and constitute useful therapeutic targets.

Effects of Global Warming on Patients with Dementia, Motor Neuron or Parkinson's Diseases: A Comparison among Cortical and Subcortical Disorders.

Exposure to global warming can be dangerous for health and can lead to an increase in the prevalence of neurological diseases worldwide. Such an effect is more evident in populations that are less prepared to cope with enhanced environmental temperatures. In this work, we extend our previous research on the link between climate change and Parkinson's disease (PD) to also include Alzheimer's Disease and other Dementias (AD/D) and Amyotrophic Lateral Sclerosis/Motor Neuron Diseases (ALS/MND). One hundred and eighty-four world countries were clustered into four groups according to their climate indices (warming and annual average temperature). Variations between 1990 and 2016 in the diseases' indices (prevalence, deaths, and disability-adjusted life years) and climate indices for the four clusters were analyzed. Unlike our previous work on PD, we did not find any significant correlation between warming and epidemiological indices for AD/D and ALS/MND patients. A significantly lower increment in prevalence in countries with higher temperatures was found for ALS/MND patients. It can be argued that the discordant findings between AD/D or ALS/MND and PD might be related to the different features of the neuronal types involved and the pathophysiology of thermoregulation. The neurons of AD/D and ALS/MND patients are less vulnerable to heat-related degeneration effects than PD patients. PD patients' substantia nigra pars compacta (SNpc), which are constitutively frailer due to their morphology and function, fall down under an overwhelming oxidative stress caused by climate warming.

A Case Study of Upper Limb Robotic-Assisted Therapy Using the Track-Hold Device.

The Track-Hold System (THS) project, developed in a healthcare facility and therefore in a controlled and protected healthcare environment, contributes to the more general and broad context of Robotic-Assisted Therapy (RAT). RAT represents an advanced and innovative rehabilitation method, both motor and cognitive, and uses active, passive, and facilitating robotic devices. RAT devices can be equipped with sensors to detect and track voluntary and involuntary movements. They can work in synergy with multimedia protocols developed ad hoc to achieve the highest possible level of functional re-education. The THS is based on a passive robotic arm capable of recording and facilitating the movements of the upper limbs. An operational interface completes the device for its use in the clinical setting. In the form of a case study, the researchers conducted the experimentation in the former Tabarracci hospital (Viareggio, Italy). The case study develops a motor and cognitive rehabilitation protocol. The chosen subjects suffered from post-stroke outcomes affecting the right upper limb, including strength deficits, tremors, incoordination, and motor apraxia. During the first stage of the enrolment, the researchers worked with seven patients. The researchers completed the pilot with four patients because three of them got a stroke recurrence. The collaboration with four patients permitted the generation of an enlarged case report to collect preliminary data. The preliminary clinical results of the Track-Hold System Project demonstrated good compliance by patients with robotic-assisted rehabilitation; in particular, patients underwent a gradual path of functional recovery of the upper limb using the implemented interface.

A System for Neuromotor Based Rehabilitation on a Passive Robotic Aid.

In the aging world population, the occurrence of neuromotor deficits arising from stroke and other medical conditions is expected to grow, demanding the design of new and more effective approaches to rehabilitation. In this paper, we show how the combination of robotic technologies with progress in exergaming methodologies may lead to the creation of new rehabilitation protocols favoring motor re-learning. To this end, we introduce the Track-Hold system for neuromotor rehabilitation based on a passive robotic arm and integrated software. A special configuration of weights on the robotic arm fully balances the weight of the patients' arm, allowing them to perform a purely neurological task, overcoming the muscular effort of similar free-hand exercises. A set of adaptive and configurable exercises are proposed to patients through a large display and a graphical user interface. Common everyday tasks are also proposed for patients to learn again the associated actions in a persistent way, thus improving life independence. A data analysis module was also designed to monitor progress and compute indices of post-stroke neurological damage and Parkinsonian-type disorders. The system was tested in the lab and in a pilot project involving five patients in the post-stroke chronic stage with partial paralysis of the right upper limb, showing encouraging preliminary results.

Using blood data for the differential diagnosis and prognosis of motor neuron diseases: a new dataset for machine learning applications.

Early differential diagnosis of several motor neuron diseases (MNDs) is extremely challenging due to the high number of overlapped symptoms. The routine clinical practice is based on clinical history and examination, usually accompanied by electrophysiological tests. However, although previous studies have demonstrated the involvement of altered metabolic pathways, biomarker-based monitoring tools are still far from being applied. In this study, we aim at characterizing and discriminating patients with involvement of both upper and lower motor neurons (i.e., amyotrophic lateral sclerosis (ALS) patients) from those with selective involvement of the lower motor neuron (LMND), by using blood data exclusively. To this end, in the last ten years, we built a database including 692 blood data and related clinical observations from 55 ALS and LMND patients. Each blood sample was described by 108 analytes. Starting from this outstanding number of features, we performed a characterization of the two groups of patients through statistical and classification analyses of blood data. Specifically, we implemented a support vector machine with recursive feature elimination (SVM-RFE) to automatically diagnose each patient into the ALS or LMND groups and to recognize whether they had a fast or slow disease progression. The classification strategy through the RFE algorithm also allowed us to reveal the most informative subset of blood analytes including novel potential biomarkers of MNDs. Our results show that we successfully devised subject-independent classifiers for the differential diagnosis and prognosis of ALS and LMND with remarkable average accuracy (up to 94%), using blood data exclusively.

Diaphragm ultrasonography in amyotrophic lateral sclerosis: a diagnostic tool to assess ventilatory dysfunction and disease severity.

BACKGROUND: Respiratory failure represents an unavoidable step in patients with amyotrophic lateral sclerosis (ALS) and other motor neuron diseases (MND). The development of diaphragm ultrasonography (DUS) provides an alternative useful and risk-free tool to supply clinical, functional, and neurophysiological assessment of respiratory muscle weakness. Our aim was to evaluate if sonographic changes (thickness and echogenicity in the costal portion of the diaphragm, at rest and during respiratory movements) may be used in ALS patients to assess disease severity over time, to rule out any risk or discomfort due to traditional neurophysiological investigations. METHODS: Twenty ALS patients (mean age, 64.6 ± 10.5 years) were enrolled and data were compared with age-matched healthy volunteers; DUS data were correlated with respiratory function and disease severity scale. Examinations were performed using Telemed Echo-wave II or Esaote MyLabGamma devices in conventional B-Mode. RESULTS: Mean resting thickness was reduced in all cases; changes in thickness during inspiration and expiration were also reduced (p < 0.0001) and lost in severe cases (n = 3). In bulbar-onset disease, respiratory scores were strictly correlated with the difference in diaphragm thickness between full inspiration-and expiration-as well as on the diaphragm thickness in expiration (p < 0.001). CONCLUSIONS: DUS represents a simple, painless, and risk-free tool; moreover, it provides useful functional and structural insights to the understanding of diaphragm function and the degree of respiratory failure in ALS.

Objective assessment of blinking and facial expressions in Parkinson's disease using a vertical electro-oculogram and facial surface electromyography.

OBJECTIVE: Hypomimia is a common and early symptom of Parkinson's disease (PD), which reduces the ability of PD patients to manifest emotions. Currently, it is visually evaluated by the neurologist during neurological examinations for PD diagnosis, as described in task 3.2 of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Since such an evaluation is semi-quantitative and affected by inter-variability, this paper aims to measure the physiological parameters related to eye blink and facial expressions extracted from a vertical electro-oculogram (VEOG) and facial surface electromyography (fsEMG) to differentiate PD patients from healthy control subjects (HCs). APPROACH: The spontaneous eye blink rate-minute (sEBR), its maximum amplitude (BMP), and facial cutaneous muscle activity were measured in 24 PD patients and 24 HCs while the subjects looked at a visual-tester composed of three main parts: static vision, dynamic vision and reading silently. Specificity and sensitivity for each parameter were calculated. MAIN RESULTS: The VEOG and the fsEMG allowed the identification of some parameters related to eye blink and facial expressions (i.e. sEBR, BMP, frontal and peribuccal muscular activities), being able to distinguish between PD patients and HCs with high sensitivity and specificity. SIGNIFICANCE: The demonstration that the combination of parameters related to eye blink and facial expressions can discriminate (with high accuracy) between PD patients versus HCs, thus resulting in a useful tool to support the neurologist in objective assessment of hypomimia for improving PD diagnosis.

Alzheimer and his disease: a brief history.

More than 100 years ago, Alois Alzheimer first described the clinical and pathological features of an unusual brain disease during the meeting of the Society of Southwest German Psychiatrists in Tübingen: the patient, Auguste Deter, suffered memory loss, disorientation, hallucinations and delusions and died at the age of 55. In 1910, Emil Kraepelin named the condition with the eponym of "Alzheimer's disease" (AD) that is, now, the most common neurodegenerative disease with more than 25 million cases worldwide and a major medical problem nearing catastrophic levels. The present article discusses Alzheimer's work in the context of his life and time.

Levodopa response in dementia with lewy bodies: a 1-year follow-up study.

PURPOSE: To evaluate levodopa responsiveness in patients with probable dementia with Lewy bodies (DLB) compared to early Parkinson's disease (PD) patients. METHODS: Twenty four cases with DLB and 21 with PD underwent a baseline assessment with UPDRS (sub-item II and III) and an acute levodopa challenge test. Positive response to acute levodopa test was defined as an improvement of at least 15% in the tapping test, and at least 25% in the walking test and rigidity or tremor score. Subsequently, all patients were treated continuously with levodopa and evaluated after 6 and 12 months by means of UPDRS II/III. RESULTS: Positive response to the acute levodopa test was observed in 55% of DLB patients (acute DLB responders), and in 90% of PD patients (acute PD responders). Acute DLB responders showed increased latency, and reduction of both duration and amplitude of response to acute levodopa in comparison with acute PD responders. At the 6-month follow-up visit, acute DLB responders showed a greater motor benefit compared with acute DLB non-responders. This improvement was similar to that observed in PD patients. However, at 1-year follow-up acute DLB responders showed a faster worsening of UPDRS III scores compared with acute PD responders, implying a reduction of levodopa efficacy. CONCLUSIONS: Positive response to acute levodopa test can occur in DLB patients and may be predictive of long-term benefit of chronic levodopa therapy, although the motor improvement is less impressive than in PD patients.

A case of idiopathic low CSF pressure headache presenting as cough headache.

Idiopathic low cerebrospinal fluid (CSF) pressure headache is considered to be one that worsens within 15 min of sitting-up or standing-up, accompanied by at least one of the following: neck stiffness, tinnitus, hypacusia, photophobia and nausea. Several reports suggest that a substantial number of idiopathic low CSF pressure cases do not present typical clinical symptoms and that a considerable clinical variability exists. We report the case of an idiopathic low CSF pressure presenting as a cough headache.

Cerebellar ataxia with complete clinical recovery and resolution of MRI lesions related to central pontine myelinolysis: case report and literature review.

There are several reports of central pontine myelinolysis (CPM) in a setting of malnutrition, alcoholism, and chronic debilitating illness associated with electrolyte abnormalities, especially hyponatremia. The cause of myelinolysis is still under debate, and, although osmotic effects are thought to be responsible in most cases, alternative pathological factors should be considered [King et al.: Am J Med Sci 2010;339:561-567]. We report a case of CPM in a patient with recent chemotherapy for colon cancer without electrolyte unbalance and otherwise unexplained causes. Moreover, the present case is an example of the unusual clinical ataxic variant, followed by complete recovery without any specific treatment. The diagnosis was confirmed by MRI, which showed a characteristic hyperintense signal abnormality in the central part of the pons with an unaffected outer rim. One month later, we observed complete resolution of clinical and radiological symptoms.