Subacute copper-deficiency myelopathy in a patient with occult celiac disease

Context: Acquired copper deficiency represents a rare cause of progressive myelopathy presenting with sensory ataxia and spastic gait. The time interval from neurological symptoms onset to diagnosis of myelopathy ranges from 2 months to several years in almost all cases, mimicking the clinical course of subacute combined degeneration due to vitamin B12 deficiency. Findings: A 60-year-old man, without any gastrointestinal symptoms, developed over the course of one week rapidly progressive gait imbalance, tingling and numbness in his feet and ascending lower limb weakness. Spine magnetic resonance imaging revealed hyperintensity involving cervical and dorsal posterior columns of spinal cord. Blood analysis revealed undetectable serum copper levels, low serum ceruloplasmin and positive serum Immunoglobulin A anti-tissue transglutaminase. Upper gastrointestinal endoscopy was performed revealing duodenal villous atrophy consistent with a malabsorption pattern. A gluten-free diet in association with intravenous then oral copper supplementation prompted sustained normalization of serum copper levels and progressive clinical improvement. Conclusion/Clinical Relevance: We report a rare case of myelopathy induced by copper deficiency secondary to undiagnosed celiac disease, peculiarly presenting with a subacute onset. This case expands the neurological presentation and clinical course of myelopathy due to acquired copper deficiency. We suggest investigation of copper deficiency in patients presenting with subacute or even acute sensory ataxia and spastic gait. Detection of hypocupremia in patients without a previous history of gastric surgery should lead to diagnostic testing for celiac disease even in the absence of any obvious gastrointestinal symptoms

Preliminary results of ON/OFF detection using an integrated system for Parkinson's disease monitoring

This paper describes the experimental set up of a system composed by a set of wearable sensors devices for the recording of the motion signals and software algorithms for the signal analysis. This system is able to automatically detect and assess the severity of bradykinesia, tremor, dyskinesia and akinesia motor symptoms. Based on the assessment of the akinesia, the ON-OFF status of the patient is determined for each moment. The assessment performed through the automatic evaluation of the akinesia is compared with the status reported by the patients in their diaries. Preliminary results with a total recording period of 32 hours with two PD patients are presented, where a good correspondence (88.2 +/- 3.7 %) was observed. Best (93.7 por ciento) and worst (87 por ciento) correlation results are illustrated, together with the analysis of the automatic assessment of the akinesia symptom leading to the status determination. The results obtained are promising, and if confirmed with further data, this automatic assessment of PD motor symptoms will lead to a better adjustment of medication dosages and timing, cost savings and an improved quality of life of the patients

Psychological adjustment and heart rate variability in ovarian cancer survivors

Introduction: Body image, posttraumatic growth, quality of life, coping, and social support are relevant concepts to ovarian cancer survivors. This study aimed to examine the associations among these concepts as well as their relationships with heart rate variability (HRV), which is an index of vagal tone. Methods: an exploratory and correlational study was conducted on 25 ovarian cancer survivors. We used self-report measures to assess psychological variables. HRV parameters recorded for this study were analyzed in the time domain and in the frequency domain. Spearman correlations were performed. Results: Positive attitude coping strategy was associated with psychological and physical distress related to problems of appearance (Rho = -.57, p < .01), emotional functioning (Rho = .53, p < .01), and global health (Rho = .47, p < .05). Problem solving coping strategy was correlated with a higher posttraumatic growth, namely greater personal strength (Rho = .44, p < .05) and better relationships with others (Rho = .40, p < .05). Seeking social support was associated with growth in relationships with others (Rho = .40, p < .05). Higher HRV parameters were associated with higher physical functioning (SDNN: Rho = .59, p < .01; RMSSD: Rho = .54; p < .01; pNN50: Rho = .56, p < .01; HF: Rho = .58, p < .01). The ratio of low-frequency to high-frequency power (LF/HF) was negatively associated with posttraumatic growth (i.e., personal strength: Rho = .51, p < .05; new possibilities: Rho = -.54, p < .01). Discussion: Positive attitude and problem solving coping strategies may facilitate psychological adjustment to ovarian cancer. The strong association between markers of vagal tone and physical functioning offers insights on the possible role of vagus nerve in ovarian cancer survivors. These findings should be further investigated by future studies with larger samples and longitudinal designs

Does a combination of ≥2 abnormal tests vs. the ERC-ESICM stepwise algorithm improve prediction of poor neurological outcome after cardiac arrest? A post-hoc analysis of the ProNeCA multicentre study.

BACKGROUND Bilaterally absent pupillary light reflexes (PLR) or N20 waves of short-latency evoked potentials (SSEPs) are recommended by the 2015 ERC-ESICM guidelines as robust, first-line predictors of poor neurological outcome after cardiac arrest. However, recent evidence shows that the false positive rates (FPRs) of these tests may be higher than previously reported. We investigated if testing accuracy is improved when combining PLR/SSEPs with malignant electroencephalogram (EEG), oedema on brain computed tomography (CT), or early status myoclonus (SM). METHODS Post-hoc analysis of ProNeCA multicentre prognostication study. We compared the prognostic accuracy of the ERC-ESICM prognostication strategy vs. that of a new strategy combining ≥2 abnormal results from any of PLR, SSEPs, EEG, CT and SM. We also investigated if using alternative classifications for abnormal SSEPs (absent-pathological vs. bilaterally-absent N20) or malignant EEG (ACNS-defined suppression or burst-suppression vs. unreactive burst-suppression or status epilepticus) improved test sensitivity. RESULTS We assessed 210 adult comatose resuscitated patients of whom 164 (78%) had poor neurological outcome (CPC 3-5) at six months. FPRs and sensitivities of the ≥2 abnormal test strategy vs. the ERC-ESICM algorithm were 0[0-8]% vs. 7 [1-18]% and 49[41-57]% vs. 63[56-71]%, respectively (p < .0001). Using alternative SSEP/EEG definitions increased the number of patients with ≥2 concordant test results and the sensitivity of both strategies (67[59-74]% and 54[46-61]% respectively), with no loss of specificity. CONCLUSIONS In comatose resuscitated patients, a prognostication strategy combining ≥2 among PLR, SSEPs, EEG, CT and SM was more specific than the 2015 ERC-ESICM prognostication algorithm for predicting 6-month poor neurological outcome

Freezing of gait in Parkinson’s disease patients treated with bilateral subthalamic nucleus deep brain stimulation: A long-term overview

Bilateral subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment in advanced Parkinson’s Disease (PD). However, the effects of STN-DBS on freezing of gait (FOG) are still debated, particularly in the long-term follow-up (&gt;/=5-years). The main aim of the current study is to evaluate the long-term effects of STN-DBS on FOG. Twenty STN-DBS treated PD patients were included. Each patient was assessed before surgery through a detailed neurological evaluation, including FOG score, and reevaluated in the long-term (median follow-up: 5-years) in different stimulation and drug conditions. In the long term follow-up, FOG score significantly worsened in the off-stimulation/off-medication condition compared with the preoperative off-medication assessment (z = -1.930; p = 0.05) but not in the on-stimulation/off-medication (z = -0.357; p = 0.721). There was also a significant improvement of FOG at long-term assessment by comparing on-stimulation/off-medication and off-stimulation/off-medication conditions (z = -2.944; p = 0.003). These results highlight the possible beneficial long-term effects of STN-DBS on FOG

Freezing of Gait in Parkinson's Disease Patients Treated with Bilateral Subthalamic Nucleus Deep Brain Stimulation: A Long-Term Overview

Bilateral subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment in advanced Parkinson's Disease (PD). However, the effects of STN-DBS on freezing of gait (FOG) are still debated, particularly in the long-term follow-up (≥5-years). The main aim of the current study is to evaluate the long-term effects of STN-DBS on FOG. Twenty STN-DBS treated PD patients were included. Each patient was assessed before surgery through a detailed neurological evaluation, including FOG score, and revaluated in the long-term (median follow-up: 5-years) in different stimulation and drug conditions. In the long term follow-up, FOG score significantly worsened in the off-stimulation/off-medication condition compared with the pre-operative off-medication assessment (z = -1.930; p = 0.05) but not in the on-stimulation/off-medication (z = -0.357; p = 0.721). There was also a significant improvement of FOG at long-term assessment by comparing on-stimulation/off-medication and off-stimulation/off-medication conditions (z = -2.944; p = 0.003). These results highlight the possible beneficial long-term effects of STN-DBS on FOG

Cortical action myoclonus due to cortical laminar necrosis

Dear Editor, Cortical myoclonus is the most common form of myoclonus, mainly affecting distal upper limbs and typically occurring during voluntary action [1]; in particular, focal cortical myoclonus is frequently caused by a focal lesion affecting excitability of the sensorimotor cortex [1]. Transcranial magnetic stimulation (TMS) evaluates the excitability state of the primary motor cortex [2], representing an important tool to study focal cortical myoclonus [3]. Cortical laminar necrosis (CLN) is defined as hyperintense cortical lesion on Magnetic Resonance Imaging (MRI) T1-weighted sequences involving specific cortical laminae observed after a subacute or chronic brain damage [4]. We here present a patient with cortical action myoclonus associated with CLN

Biological and biophysics aspects of metformin-induced effects: Cortex mitochondrial dysfunction and promotion of toxic amyloid pre-fibrillar aggregates

The onset of Alzheimer disease (AD) is influenced by several risk factors comprising diabetes. Within this context, antidiabetic drugs, including metformin, are investigated for their effect on AD. We report that in the C57B6/J mice, metformin is delivered to the brain where activates AMP-activated kinase (AMPK), its molecular target. This drug affects the levels of β- secretase (BACE1) and β-amyloid precursor protein (APP), promoting processing and aggregation of β-amyloid (Aβ), mainly in the cortex region. Moreover, metformin induces mitochondrial dysfunction and cell death by affecting the level and conformation of Translocase of the Outer Membrane 40 (TOM40), voltage-dependent anion-selective channels 1 (VDAC1) and hexokinase I (HKI), proteins involved in mitochondrial transport of molecules, including Aβ. By using biophysical techniques we found that metformin is able to directly interact with Aβ influencing its aggregation kinetics and features. These findings indicate that metformin induces different adverse effects, leading to an overall increase of the risk of AD onset

Pearls & Oy-sters: Paroxysmal dysarthria-ataxia syndrome: Acoustic analysis in a case of antiphospholipid syndrome

Pearls: Paroxysmal dysarthria-ataxia syndrome (PDA), first described by Parker in 1946, is characterized by paroxysmal and stereotyped repeated daily episodes of sudden ataxic symptoms associated with dysarthric speech lasting from few seconds to minutes.1 During the episodes, patients present with slow speech, irregular articulatory breakdown, dysprosodia, hypernasality, variable pitch and loudness, and prolonged intervals, consistent with perceptual characteristics of ataxic dysarthria.2,3 PDA is a rare neurologic manifestation of either genetic or acquired conditions.2 The most frequent genetic diseases occurring with PDA are episodic ataxias, a group of dominantly inherited disorders characterized by transient and recurrent episodes of truncal instability and limbs incoordination triggered by exertion or emotional stress.4 Among acquired conditions, PDA has been reported mainly in multiple sclerosis (MS), in other immunomediated diseases, or in ischemic stroke.5,–,7 The common finding among these diseases is the involvement of cerebellar pathways, specifically the crossed fibers of cerebello-thalamocortical pathway in the lower midbrain. Indeed, most of the reported cases of PDA suggest that the responsible lesion is located in the midbrain, near or in the red nucleus,8 where a lesion frequently reveals with dysarthria.9,10 Oy-sters: Until now, the pathophysiologic basis of PDA remains unknown, as well as the characterization of dysarthria during PDA. We present a case of PDA in a patient with antiphospholipid syndrome (APS) evaluated with an acoustic and perceptual analysis of speech to determine the specific pattern of paroxysmal dysarthria