Central Nervous Disorders Research Articles

Charcot neuroarthropathy of the hand in a diabetic patient after upper extremity trauma

Charcot neuroarthropathy is a progressive degenerative arthritis which affects nearly every joint of the body associated with an underlying central or peripheral neurological disorder and can cause severe disability. The joints most frequently involved are lower limbs especially foot, shoulder and elbow. However, Charcot neuroarthropathy of the hand is quite rare. Herein, we present a 50-year-old diabetic female patient with Charcot neuroarthropathy of the right hand after upper extremity trauma. Major or minor traumas in diabetic patients can increase the risk of Charcot neuroarthropathy on upper extremity as a complication of diabetes mellitus.

Central and peripheral aspects of noise-induced hearing loss

Noise is an important socioeconomic problem in industrialized countries. Development of efficient treatment options for the audiological phenomena resulting from noise-induced hearing loss requires in-depth understanding of the underlying damage mechanisms causing peripheral and central nervous changes. Mechanical damage, ischemia and excitotoxicity are mainly responsible for noise-induced cell death and biophysical changes in the cochlea. Auditory synaptopathy is an additional consequence. Besides these cochlear pathologies, noise exposure leads to extensive changes within the central auditory pathway. Overstimulation causes early cell loss in the ventral cochlear nucleus just after noise exposure, which is in accordance with enhancement of apoptotic mechanisms within the corresponding timeframe. In contrast to the cell loss in lower auditory structures due to overstimulation, the later significant reduction of cell density in higher auditory structures is due to sensory deprivation. Changes in network homeostasis seem to partially compensate structural losses by modulation of spontaneous activity. However, central nervous processing of auditory information is permanently impaired by the neuroplastic changes. Unfortunately, the various noise-induced peripheral and central pathologies are difficult to treat. New therapeutic approaches are required, particularly for treatment of central nervous processing disorders and auditory synaptopathy, which contribute to audiological phenomena such as tinnitus, hyperacusis and poor speech perception in noise.

Perinatal Outcomes After Treatment With ADHD Medication During Pregnancy.

To analyze perinatal outcomes after maternal use of attention-deficit/hyperactivity disorder (ADHD) medication during pregnancy. The study included singletons born between 2006 and 2014 in Sweden. Data on prescription drug use, pregnancies, deliveries, and the newborn infants' health were obtained from the Swedish Medical Birth Register, the Prescribed Drug Register, and the Swedish Neonatal Quality Register. We compared infants exposed to ADHD medication during pregnancy with infants whose mothers never used these drugs and infants whose mothers used ADHD medication before or after pregnancy. Analyses were performed with logistic regression. Among 964 734 infants, 1591 (0.2%) were exposed to ADHD medication during pregnancy and 9475 (1.0%) had mothers treated before or after pregnancy. Exposure during pregnancy increased the risk for admission to a NICU compared with both no use and use before or after pregnancy (adjusted odds ratio [aOR], 1.5; 95% confidence interval [CI], 1.3-1.7; and aOR, 1.2; 95% CI, 1.1-1.4, respectively). Infants exposed during pregnancy had more often central nervous system-related disorders (aOR, 1.9; 95% CI, 1.1-3.1) and were more often moderately preterm (aOR, 1.3; 95% CI, 1.1-1.6) than nonexposed infants. There was no increased risk for congenital malformations or perinatal death. Treatment with ADHD medication during pregnancy was associated with a higher risk for neonatal morbidity, especially central nervous system-related disorders such as seizures. Because of large differences in background characteristics between treated women and controls, it is uncertain to what extent this can be explained by the ADHD medication per se.

Clippers syndrome in a young patient with ataxia and dizziness

Introduction Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids: A rare central nervous system inflammatory disorder involving predominantly the pons as a distinct form of brainstem encephalitis centered on the pons, and/or the spinal cord. Usually presented with symptoms/signs referable to brainstem, cranial nerve-and/or cerebellar dysfunction. Symptoms related to long tract affections and/or spinal cord syndrome. Paresis, spasticity, plantar response, hyperreflexia, altered sensation of the extremities, decrease vibration sense, neurogenic bladder and cognitive deficits. Responsive to steroids and long term immunosuppression. MRI with contrast is a useful tool to help for early diagnosis of such cases. Case description Here we are going to report a case of a 28-year-old, previously healthy female presented to the ED with a history of blurring of vision, dizziness, headache, and parasthesia of lower limbs, not alcoholic or smoker, no H/O drug intake. No family history of chronic disease. On examination the patient had normal vital signs (Temp. 37.2, RR 18 and SpO2 100%) her ENT examination is unremarkable. Her neck movements are unrestricted. Cardiovascular, respiratory and abdominal examinations are unremarkable. Her pupils are equal and reactive; fundoscopy is normal. She is orientated and follows commands, horizontal Nystagmus, DTRS exaggerated symmetrically, planter reflex down going on the left equivocal on the right, positive Romberg sign to the left and dysdiadochokinesis. Results and conclusions Non contrast CT head showed left periventricular parenchyma calcification suspicious of hemorrhagic spots. MRI brain showed multiple punctuate and curvilinear enhancing foci, B/L cerebral scattered ovoid bright signal intensity ring enhancement small nodules workup was done to exclude Meningitis, TB encephalitis, CNS lymphoma, Toxoplasmosis, HIV, Vasculitis and Demyelination. Results were negative. Steroids started and the patient improved. Take-home message Careful history taking and a high index of suspicion of central causes of vertigo is needed when a patient presents with dizziness.

Triple reuptake inhibitors: Design, synthesis and structure–activity relationship of benzylpiperidine–tetrazoles

Monoamine transporters are important targets in the treatment of various central nervous disorders. Several limitations of traditional reuptake inhibitors, like delayed onset of action, insomnia, and sexual dysfunction, have compelled the search for safer, more effective compounds. In this study, we have sought to identify novel monoamine reuptake inhibitors. Based upon the docking study of compounds that we had reported previously, aromatic rings (A1) were modified to generate a novel series of benzylpiperidine–tetrazoles. Thirty-one compounds were synthesized and evaluated for their triple reuptake inhibition of serotonin, norepinephrine and dopamine. Triple reuptake inhibitor, compound 2q, in particular, showed potent serotonin reuptake inhibition, validating our design approach.

Hypertensive encephalopathy mimicking cerebral vasculitis with pontine oedema, cerebellar white matter lesions and multiple cerebral infarctions

A 47-year-old man with poorly controlled hypertension presented with headaches, right-sided weakness and dysarthria. CT and MRI scans of the brain showed widespread abnormalities including significant pontine oedema, basal ganglia...

ANTI AQUAPORIN 4 POSITIVE NEUROMYELITIS OPTICA SPECTRUM DISORDER AND PRIMARY SJÖGREN SYNDROME FOLLOWING SUCCESSFUL THERAPY FOR CHRONIC HEPATITIS C – REPORT OF A CLINICAL CASE

Neuromyelitis optica spectrum disorders (NMOSD) are a heterogeneous group of potentially disabling central nervous system inflammatory disorders. Association with other organ-specific or multisystem autoimmune disorders is commonly encountered. We report the case of a Caucasian woman with AQP4-IgG positive NMOSD and primary Sjögren syndrome - previously reported as a poster at the 14th Congress of the Romanian Society of Neurology (abstract published in ROJN, Vol. XV, Suppl). The clinical onset followed the successful treatment of chronic hepatitis C with interferon alpha and ribavirin. To the best of our knowledge, similar clinical presentations have not been described. The etiopathogenic treatment included high dose methylprednisolone, immune suppression with cyclophosphamide, and periodic plasma exchanges. In spite of an active disease with very high baseline AQP4-IgG titres, during the four years of treatment the patient has had only one relapse and has no residual disability.

Acute Onset Neurological Disorders during Pregnancy: A Literature Review.

Objectives To characterize the most common peripheral and central neurological disorders during pregnancy. Methods Original research and review of the literature on neurological complications during pregnancy. We searched for keywords related to the topic on different databases. Results Pregnancy involves physiological changes that can trigger peripheral neurological and/or central nervous system pathologies, which can sometimes be associated with hypertensive disorders. A definitive diagnosis of neurological disorders can be made according to the trimester of pregnancy and the clinical findings. Carpal tunnel syndrome and peripheral facial palsy are common peripheral neurological disorders, more frequent in the second half of pregnancy. Central nervous disorders are more complex and a precise diagnosis must be made in order to improve perinatal outcomes, provide correct management and treatment and to prevent acute and long-term complications. Conclusions It is possible to achieve a precise diagnosis, management and treatment of neurological disorders during pregnancy, but these require a multidisciplinary approach, crucial to improve perinatal outcomes.

European consensus on the concepts and measurement of the pathophysiological neuromuscular responses to passive muscle stretch.

To support clinical decision-making in central neurological disorders, a physical examination is used to assess responses to passive muscle stretch. However, what exactly is being assessed is expressed and interpreted in different ways. A clear diagnostic framework is lacking. Therefore, the aim was to arrive at unambiguous terminology about the concepts and measurement around pathophysiological neuromuscular response to passive muscle stretch. During two consensus meetings, 37 experts from 12 European countries filled online questionnaires based on a Delphi approach, followed by plenary discussion after rounds. Consensus was reached for agreement ≥75%. The term hyper-resistance should be used to describe the phenomenon of impaired neuromuscular response during passive stretch, instead of for example 'spasticity' or 'hypertonia'. From there, it is essential to distinguish non-neural (tissue-related) from neural (central nervous system related) contributions to hyper-resistance. Tissue contributions are elasticity, viscosity and muscle shortening. Neural contributions are velocity dependent stretch hyperreflexia and non-velocity dependent involuntary background activation. The term 'spasticity' should only be used next to stretch hyperreflexia, and 'stiffness' next to passive tissue contributions. When joint angle, moment and electromyography are recorded, components of hyper-resistance within the framework can be quantitatively assessed. A conceptual framework of pathophysiological responses to passive muscle stretch is defined. This framework can be used in clinical assessment of hyper-resistance and will improve communication between clinicians. Components within the framework are defined by objective parameters from instrumented assessment. These parameters need experimental validation in order to develop treatment algorithms based on the aetiology of the clinical phenomena.

Different Molecular Mechanisms Mediate Direct or Glia-Dependent Prion Protein Fragment 90-231 Neurotoxic Effects in Cerebellar Granule Neurons.

Glia over-stimulation associates with amyloid deposition contributing to the progression of central nervous system neurodegenerative disorders. Here we analyze the molecular mechanisms mediating microglia-dependent neurotoxicity induced by prion protein (PrP)90-231, an amyloidogenic polypeptide corresponding to the protease-resistant portion of the pathological prion protein scrapie (PrPSc). PrP90-231 neurotoxicity is enhanced by the presence of microglia within neuronal culture, and associated to a rapid neuronal [Ca++] i increase. Indeed, while in "pure" cerebellar granule neuron cultures, PrP90-231 causes a delayed intracellular Ca++ entry mediated by the activation of NMDA receptors; when neuron and glia are co-cultured, a transient increase of [Ca++] i occurs within seconds after treatment in both granule neurons and glial cells, then followed by a delayed and sustained [Ca++] i raise, associated with the induction of the expression of inducible nitric oxide synthase and phagocytic NADPH oxidase. [Ca++] i fast increase in neurons is dependent on the activation of multiple pathways since it is not only inhibited by the blockade of voltage-gated channel activity and NMDA receptors but also prevented by the inhibition of nitric oxide and PGE2 release from glial cells. Thus, Ca++ homeostasis alteration, directly induced by PrP90-231 in cerebellar granule cells, requires the activation of NMDA receptors, but is greatly enhanced by soluble molecules released by activated glia. In glia-enriched cerebellar granule cultures, the activation of inducible nitric oxide (iNOS) and NADPH oxidase represents the main mechanism of toxicity since their pharmacological inhibition prevented PrP90-231 neurotoxicity, whereas NMDA blockade by D(-)-2-amino-5-phosphonopentanoic acid is ineffective; conversely, in pure cerebellar granule cultures, NMDA blockade but not iNOS inhibition strongly reduced PrP90-231 neurotoxicity. These data indicate that amyloidogenic peptides induce neurotoxic signals via both direct neuron interaction and glia activation through different mechanisms responsible of calcium homeostasis disruption in neurons and potentiating each other: the activation of excitotoxic pathways via NMDA receptors and the release of radical species that establish an oxidative milieu.

Microbiota abnormalities and the therapeutic potential of probiotics in the treatment of mood disorders.

Major depressive disorder (MDD) and bipolar disorder (BD) are among the leading causes of burden and disability worldwide. Despite intensified research efforts to improve the treatment options and remission rates in mood disorders, no disease modifying treatment exists for these disorders. Accumulating evidence implicates the involvement of the gut microbiota in processes relevant to etiopathology of central nervous system-based disorders. The objective of this article was to critically evaluate the evidence supporting the link between gastrointestinal microbiota and mood disorders and to discuss the potential benefits of using probiotics in the treatment of MDD and BD. The concept of psychobiotics, which is bacterial-based interventions with mental health benefit, is emerging in the field. On the other hand, while probiotics might potentially represent a significant advance, specific roles of microbiota in the pathophysiology of mood disorders still need further investigation along with intervention studies.

Primary central nervous system posttransplant lymphoproliferative disorder after solid organ transplantation: report of four cases with distinct clinical characteristics (P3.162)

Primary central nervous system posttransplant lymphoproliferative disorder after solid organ transplantation: report of four cases with distinct clinical characteristics (P3.162)

Purinergic Signalling and Neurological Diseases: An Update.

Purinergic signalling, i.e. ATP as an extracellular signalling molecule and cotransmitter in both peripheral and central neurons, is involved in the physiology of neurotransmission and neuromodulation. Receptors for purines have been cloned and characterised, including 4 subtypes of the P1(adenosine) receptor family, 7 subtypes of the P2X ion channel nucleotide receptor family and 8 subtypes of the P2Y G protein-coupled nucleotide receptor family. The roles of purinergic signalling in diseases of the central nervous system and the potential use of purinergic compounds for their treatment are attracting increasing attention. In this review, the focus is on the findings reported in recent papers and reviews to update knowledge in this field about the involvement of purinergic signalling in Alzheimer's, Parkinson's and Huntington's diseases, multiple sclerosis, amyotrophic lateral sclerosis, degeneration and regeneration after brain injury, stroke, ischaemia, inflammation, migraine, epilepsy, psychiatric disorders, schizophrenia, bipolar disorder, autism, addiction, sleep disorders and brain tumours. The use in particular of P2X7 receptor antagonists for the treatment of neurodegenerative diseases, cancer, depression, stroke and ischaemia, A2A receptor antagonists for Parkinson's disease and agonists for brain injury and depression and P2X3 receptor antagonists for migraine and seizures has been recommended. P2Y receptors have also been claimed to be involved in some central nervous disorders.

Syndrome of inappropriate antidiuretic hormone secretion associated with seronegative neuromyelitis optica spectrum disorder.

The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a potential cause of hyponatremia of the central nervous system (CNS). Although SIADH has been reported to be associated with many other central nervous disorders, its association with neuromyelitis optica (NMO) or NMO spectrum disorders are rare. NMO is a demyelinating disorder characterized by optic neuritis and transverse myelitis. Aquaporin-4 (AQP4), which is the target antigen for a NMO autoantibody, is the predominant CNS water channel. However, some NMO patients show seronegative AQP4 antibody results. The spectrum of NMO has been changed, and new findings about the disease have been reported. Here, we report a case of seronegative NMO spectrum disorder associated with SIADH.

Physiological and Pathological Roles of 15-Deoxy-Δ12,14-Prostaglandin J2 in the Central Nervous System and Neurological Diseases.

Prostaglandins (PGs) are divided into conventional PGs, e.g., PGD2, and cyclopentenone-type PGs, e.g., 15-deoxy-Δ12,14 prostaglandin J2 (15d-PGJ2). PGD2 is non-enzymatically metabolized to PGJ2, Δ12-PGJ2, and 15d-PGJ2. In the central nervous system, 15d-PGJ2 differentiates embryonic midbrain cells into dopaminergic neuronal cells via its nuclear peroxysome proliferator-activated receptor-γ (PPARγ). 15d-PGJ2 exerts conflict actions: proinflammatory and anti-inflammatory activities. In the brain, 15d-PGJ2 possesses opposite functions as a neuroprotectant at low concentrations and a neurotoxicant at high concentrations in the brain. PPARγ contributes to the neuroprotective effect of 15d-PGJ2 but not to the neurotoxic effect. Its membrane receptor, chemoattractant receptor-homologous molecule expressed on T-helper type 2 cells (CRTH2), is not also involved in the neurotoxicity of 15d-PGJ2. 15d-PGJ2 induces neuronal apoptosis via inactivating ubiquitin proteasome pathway and activating caspase cascade. Alternatively, 15d-PGJ2 downregulates phosphoinositide 3-kinase (PI3K)-Akt pathway and suppresses neurite outgrowth. 15d-PGJ2 possesses α,β-unsaturated ketone moiety in its cyclopentenone ring and acts an endogenous electrophile. By the Michael addition reaction, 15d-PGJ2 is covalently bound to cellular nucleophiles, such as free cysteine residues of proteins that regulate intracellular signaling pathways. There are specific binding sites of [3H]15d-PGJ2 in the plasma membrane of cerebral cortices. Besides CRTH2, plasmalemmal glycolytic enzymes, respiratory chain enzymes, molecular chaperones, adaptor proteins and cytoskeletons are identified as membrane targets for 15d-PGJ2. In the present review, we provide evidences for pathophysiological roles of 15d-PGJ2 in the central nervous system and neurological diseases.

Presentations to an urban emergency department in Bern, Switzerland associated with acute recreational drug toxicity

BackgroundAlthough the recreational use of psychoactive substances is common there is only limited systematic collection of data on acute drug toxicity or hospital presentations. Currently, data from Switzerland are only available from the University Hospital of Basel. The present study aimed to describe the presentations due to recreational drug use at an emergency department in Bern, Switzerland during a 4 year period.MethodsRetrospective analysis of cases presenting from May 2012 to April 2016 at the emergency department of the University Hospital of Bern, Switzerland, with symptoms/signs consistent with acute toxicity of recreational drug use. The cases were retrieved using a comprehensive full-text search algorithm of the electronic health records. Isolated ethanol intoxications were excluded.ResultsDuring the study period, 503 of the 157,328 emergency department attendances were directly related to acute toxicity of substances used recreationally. The mean patient age was 33 years (range 16–74), 68% were male. Alcohol co-ingestion was reported in 54% of the cases, and use of more than one recreational drug in 37% of the cases. Most presentations were related to cocaine (29%), cannabis (26%), heroin (20%) and benzodiazepines/sedatives (18%). Urine drug screening immunoassay was available in 277 cases (55%). The most frequently detected substances were cannabis (29%), cocaine (22%), benzodiazepines (21%) and opioids excluding methadone (20%). There were only two intoxications with novel psychoactive substances (NPSs): One with methylone and one with 2,5-dimethoxy-4(n)-propylphenethylamine (2C-P). The majority of patients (58%) displayed impaired consciousness (Glasgow Coma Scale (GCS) <15) upon presentation and/or pre-hospital; 21% were unconscious (GCS <8). Other frequent symptoms were agitation (36%), tachycardia (29%), and anxiety (24%). Severe complications included two fatalities, three acute myocardial infarctions, two intracranial haemorrhages, as well as psychosis and seizures in 71 and 26 cases, respectively.ConclusionsMost medical problems related to recreational drug use were associated with cocaine and cannabis use and were mainly characterised by central nervous system depression, sympathomimetic toxicity and/or psychiatric disorders. Presentations related to acute toxicities of NPSs appear to be uncommon, while prescription drugs were after classical recreational drugs the substances most commonly reported.

Lesions of the posterior limb of the internal capsule in neuromyelitis optica spectrum disorder

Posterior limb of the internal capsule lesions (PLICL) are one of the MRI features of neuromyelitis optica spectrum disorder (NMOSD). However, there is no evidence that such lesions are pathogenically related to NMOSD. We retrospectively analyzed features of PLICL in NMOSD, and other central nervous system inflammatory disorders, in 561 patients. We also examined the pathological samples of six patients. Of the 561 patients investigated, PLICL were found in 65 patients (11.6%). Lesions were bilateral in 26 cases (40%) and unilateral in 39 cases (60%). Unilateral lesions were mainly located on the left side (74.3%, 29/39). Of the 65 patients with PLICL, 46 patients had NMOSD (70.8%) and were positive for anti-aquaporin (AQP4-IgG), four had NMOSD (6.2%) and were AQP4-IgG negative, 10 patients had multiple sclerosis (MS), three patients had NMDAR encephalitis, and two had autoimmune meningoencephalitis. Of the six patients whose pathological samples were evaluated, all had PLICL and were negative for AQP4-IgG, and none had pathological NMOSD lesion features. These cases included three patients with multiple sclerosis, one with anti-N-methyl-D-aspartate receptor encephalitis, and two with autoimmune meningoencephalitis. In conclusion, PLICL are found not only in patients with NMOSD, but also in MS and other disorders.

New olfactometric findings in Parkinson's disease.

To investigate in Parkinson's disease-affected patients a correlation between hyposmia and gastrointestinal dysfunction and their possible identical etiopathogenesis. Retrospective cohort study. ENT and neurology departments (Gemelli Hospital, Rome, Italy). A total of 78 patients with diagnosis of PD according to the UK Brain Bank criteria. informed consent and olfactory testing executed; exclusion criteria: signs of dementia according to the DSM-IV criteria; Mini Mental State Examination score ≤26; head trauma; central neurological disorders, nasal or systemic diseases potentially affecting olfactory function. Motor condition was assessed by means of Hoehn and Yahr staging and by section III of the Unified PD Rating Scale, performed off and on medications. The patients underwent olfactory evaluation (TDI score), after rhinomanometry with nasal decongestion. A total of 25 non-motor symptoms were evaluated through an interview. Olfactory dysfunction was objectively found in 91.0% of patients, a percentage higher than the subjective hyposmia reported (55.1%) P = 0.0001. Seven patients (9.0%) were normosmic, 49 (62.8%) hyposmic and 22 (28.2%) anosmic. Subjective hyposmia, constipation, bloating and dyspepsia differed across groups, being higher in anosmic and hyposmic ones than in the normosmic group. P value was ≤0.05 for each symptom. Despite the original results, this study has the limitation of being based on subjective ratings by a relatively limited group of patients. Hyposmia and gastrointestinal symptoms are correlated, and this would support a possible common origin; the CNS could be reached through two different pathways, both starting in the peripheral nervous system.

Computed tomographic findings and treatment of a bull with pituitary gland abscess

BackgroundIn cattle, the prognosis of brain abscess is unfavourable and treatment is therefore not recommended. To the knowledge of the authors, there has been no report of successful treatment of a brain abscess in cattle.This report describes the clinical, computed tomographic and postmortem findings in a Holstein–Friesian bull with a hypophyseal abscess.Case reportThe main clinical findings were generalised ataxia, ptyalism, prolapse of the tongue, dropped jaw, dysphagia, head tilt and unilateral ptosis. Cerebrospinal fluid evaluation revealed 2437 leukocytes/µl and severe pleocytosis. CT examination of the head showed a cavitary lesion consistent with an abscess in the hypophysis. Treatment consisted of gentamicin and flunixin meglumine for 3 days and amoxicillin for 40 days. The neurological signs resolved within 8 days of the start of treatment. The bull was slaughtered 11 months later because of infertility, and a postmortem examination was carried out. Histologically, a mild chronic non suppurative meningoencephalitis restricted to the ventral diencephalon was diagnosed. In addition, there was mild to moderate multifocal chronic lymphoplasmacytic hypophysitis with mild multifocal fibrosis.ConclusionsThis case report stresses the significance of CT in confirming the clinical and laboratory diagnosis of central nervous system disorders in cattle and for localising brain lesions. Treatment of the brain abscess resulted, with respect to the central nervous disorder, in a successful outcome and was encouraging considering that most cases have an unfavourable prognosis.

Characterisation and cellular uptake of polysorbate 80-coated PLA nanoparticles

The blood brain-barrier is a major obstacle in the treatment of several central nervous disorders. In this context polysorbate 80-coated nanoparticles, which are quite well characterised concerning their behaviour in vivo, are an often described approach to enable transport of certain drugs into the brain. In the present study we prepared polysorbate 80-coated nanoparticles based on poly(lactid acid) and quantified the amount of adsorbed polysorbate 80 spectrophotometrically. In order to receive information about the behaviour in biological systems we analysed the protein corona by SDS-PAGE and finally investigated the cellular uptake in dependence of a previous incubation with fetal bovine serum.