Pseudobulbar Affect – A Disabling but Under-recognised Consequence of Neurological Disease and Brain Injury

2013 ◽  
Vol 8 (2) ◽  
pp. 74 ◽  
Author(s):  
Jeffrey Cummings ◽  
James Gilbart ◽  
Grethe Andersen ◽  
◽  
◽  
...  
Keyword(s):  
Brain Injury ◽  
Emotional Processing ◽  
Neurological Diseases ◽  
Neural Pathways ◽  
Motor Functioning ◽  
Pseudobulbar Affect ◽  
Care Givers ◽  
Significant Efficacy ◽  
Favourable Safety ◽  
Favourable Safety Profile

Pseudobulbar affect (PBA) is a condition associated with common neurological diseases or brain injury that manifests as uncontrollable and inappropriate outbursts of laughter or crying. PBA exacts a severe burden on the patient and care-givers in terms of reduced social functioning and often results in the patient’s isolation. The pathophysiology of PBA is incompletely understood, but symptoms are thought to result from damage to neural pathways associated with motor functioning and emotional processing. Data suggest that PBA is under-recognised by neurologists and psychiatrists and many cases go unrecognised or misdiagnosed. PBA has been successfully treated with psychoactive drugs, including antidepressants, but these do not have regulatory approval for use in this indication. A combination of dextromethorphan hydrobromide and quinidine sulphate (DM/Q) has demonstrated significant efficacy in reducing PBA symptoms and a favourable safety profile in a series of clinical trials and in regular clinical use. With the availability of an effective treatment for PBA symptoms, it becomes even more pressing to detect the condition so that patients can receive appropriate treatment.

Evidence on the New Drug Lumateperone (ITI-007) for Psychiatric and Neurological Disorders

2020 ◽  
Vol 19 (4) ◽  
pp. 243-247
Author(s):  
Marianna Mazza ◽  
Giuseppe Marano ◽  
Gianandrea Traversi ◽  
Gabriele Sani ◽  
Luigi Janiri
Keyword(s):  
Sleep Disturbances ◽  
Bipolar Depression ◽  
Neurological Diseases ◽  
D1 Receptors ◽  
Serotoninergic System ◽  
Binding Affinities ◽  
Favourable Safety ◽  
Favourable Safety Profile ◽  
Unique Mechanism

: Lumateperone (ITI-007) is a tosylate salt with binding affinities to receptors implicated in the therapeutic actions of antipsychotic medications, including the serotonin 5HT2A receptors, dopamine D2 and D1 receptors and the serotonin transporter. It has a unique mechanism of action because it simultaneously modulates serotonin, dopamine, and glutamate neurotransmission, implicated in serious mental illness. It can be considered a multi-target-directed ligand and a multifunctional modulator of serotoninergic system with possible precognitive, antipsychotic, antidepressant and anxiolytic properties. Lumateperone has been investigated as a novel agent for the treatment of schizophrenia, but it represents a new potential option for other psychiatric and neurological diseases, such as behavioural symptoms of dementia or Alzheimer’s disease, sleep disturbances, bipolar depression. Besides, it has demonstrated a favourable safety profile without significant extrapyramidal side effects, hyperprolactinemia or changes in cardiometabolic or endocrine factors versus placebo. Additional studies are warranted to confirm and examine the benefit of lumateperone and possible therapeutic targets. This paper is a comprehensive and thorough summary of the most important findings and potential future role of this particular compound in personalized treatments.

scholarly journals Ibrexafungerp: A First-in-Class Oral Triterpenoid Glucan Synthase Inhibitor

2021 ◽  
Vol 7 (3) ◽  
pp. 163 ◽  
Author(s):  
Sabelle Jallow ◽  
Nelesh P. Govender
Keyword(s):  
Pathogenic Fungi ◽  
Candida Spp ◽  
Fungal Cell ◽  
Favourable Safety ◽  
Favourable Safety Profile ◽  
Synthase Inhibitor ◽  
Increased Activity ◽  
In Vitro Data

Ibrexafungerp (formerly SCY-078 or MK-3118) is a first-in-class triterpenoid antifungal or “fungerp” that inhibits biosynthesis of β-(1,3)-D-glucan in the fungal cell wall, a mechanism of action similar to that of echinocandins. Distinguishing characteristics of ibrexafungerp include oral bioavailability, a favourable safety profile, few drug–drug interactions, good tissue penetration, increased activity at low pH and activity against multi-drug resistant isolates including C. auris and C. glabrata. In vitro data has demonstrated broad and potent activity against Candida and Aspergillus species. Importantly, ibrexafungerp also has potent activity against azole-resistant isolates, including biofilm-forming Candida spp., and echinocandin-resistant isolates. It also has activity against the asci form of Pneumocystis spp., and other pathogenic fungi including some non-Candida yeasts and non-Aspergillus moulds. In vivo data have shown IBX to be effective for treatment of candidiasis and aspergillosis. Ibrexafungerp is effective for the treatment of acute vulvovaginal candidiasis in completed phase 3 clinical trials.

scholarly journals Einsatz von Secukinumab bei Patienten mit Psoriasis und Psoriasis-Arthritis – Ergebnisse einer nichtinterventionellen Studie unter Praxisbedingungen (SERENA-Studie)

2021 ◽  
pp. 1-3
Author(s):  
Michael Sticherling
Keyword(s):  
Observational Study ◽  
Real World ◽  
Human Monoclonal Antibody ◽  
Rapid Onset ◽  
Onset Of Action ◽  
The Real ◽  
Interleukin 17A ◽  
Favourable Safety ◽  
Favourable Safety Profile

<b>Introduction:</b> Secukinumab, a fully human monoclonal antibody that directly inhibits interleukin-17A, has demonstrated robust efficacy in the treatment of moderate to severe psoriasis (PsO), psoriatic arthritis (PsA) and ankylosing spondylitis (AS), with a rapid onset of action, sustained long-term clinical responses and a consistently favourable safety profile across phase 3 trials. Here, we report the clinical data at enrolment from SERENA, designed to investigate the real-world use of secukinumab across all three indications. <b>Methods:</b> SERENA is an ongoing, longitudinal, observational study conducted at 438 sites across Europe in patients with moderate to severe plaque PsO, active PsA or active AS. Patients should have received at least 16 weeks of secukinumab treatment before enrolment in the study. <b>Results:</b> Overall 2800 patients were included in the safety set; patients with PsA (N = 541) were older than patients with PsO (N = 1799) and patients with AS (N =  460); patients with PsO had a higher mean body weight than patients with PsA and patients with AS; and patients with PsO and patients with AS were predominantly male. Time since diagnosis was longer in patients with PsO compared with patients with PsA and patients with AS, and about 40% of patients were either current or former smokers. The proportion of obese patients (body mass index ≥ 30 kg/m<sup>2</sup>) was similar across indications. Patients were treated with secukinumab for a mean duration of 1 year prior to enrolment (range 0.89–1.04). The percentages of patients with prior biologics exposure were 31.5% PsO, 59.7% PsA and 55% AS. The percentages of patients prescribed secukinumab monotherapy were 75% (n =  1349) in PsO, 48.2% (n = 261) in PsA and 48.9% (n = 225) in AS groups. <b>Conclusion:</b> Baseline demographics of the study population are consistent with existing literature. This large observational study across all secukinumab indications will provide valuable information on the long-term effectiveness and safety of secukinumab in the real-world setting.

Caracole as a Potential Neuroprotective Agent for Neurological Diseases: A Systematic

2021 ◽  
Vol 20 ◽  
Author(s):  
Mohammad Zamanian ◽  
Małgorzata Kujawska ◽  
Marjan Nikbakht Zadeh ◽  
Amin Hassanshahi ◽  
Soudeh Ramezanpour ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Traumatic Brain Injury ◽  
Parkinson's Disease ◽  
Brain Injury ◽  
Neurological Diseases ◽  
Antioxidant Systems ◽  
Neuroprotective Agent ◽  
The Impact

Background & objective: Neurological diseases are becoming a significant problem worldwide, with the elderly at a higher risk of being affected. Several researchers have investigated the neuroprotective effects of Carvacrol (CAR) (5-isopropyl-2-methyl phenol). This review systematically surveys the existing literature on the impact of CAR when used as a neuroprotective agent in neurological diseases. Methods: The systematic review involved English articles published in the last ten years obtained from PubMed, Google Scholar, and Scopus databases. The following descriptors were used to search the literature: “Carvacrol” [Title] AND “neuroprotective (neuroprotection)” [Title] OR “stroke, traumatic brain injury, Alzheimer's disease, Parkinson's disease, seizure, epilepsy [Title]. Results: : A total of 208 articles were retrieved during the search process, but only 20 studies met the eligibility criteria and were included for review. A total of 20 articles were identified, in which the efficacy of CAR was described in experimental models of stroke, traumatic brain injury, Parkinson’s disease, Alzheimer’s disease, , epilepsy, and seizure, through motor deficits improvements in neurochemical activity, especially antioxidant systems, reducing inflammation, oxidative stress and apoptosis as well as inhibition of TRPC1 and TRPM7. Conclusion : The data presented in this study support the beneficial impact of CAR on behavioural and neurochemical deficits. CAR benefits accrue because of its anti-apoptotic, antioxidant, and anti-inflammatory properties. Therefore, CAR has emerged as an alternative treatment for neurological disorders based on its properties.

scholarly journals Durvalumab in NSCLC: latest evidence and clinical potential

2018 ◽  
Vol 10 ◽  
pp. 175883591880415 ◽  
Author(s):  
Nerea Muñoz-Unceta ◽  
Isabel Burgueño ◽  
Elizabeth Jiménez ◽  
Luis Paz-Ares
Keyword(s):  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Significant Activity ◽  
Unresectable Stage ◽  
Favourable Safety ◽  
Favourable Safety Profile ◽  
Nsclc Patients

Advances in immunotherapy have led to radical improvements in outcomes, including overall survival, such as in non-small cell lung cancer (NSCLC) patients with metastatic disease treated with immune checkpoint inhibitors. More recently, promising results have been obtained in earlier disease settings, and combinations with other therapies are being actively investigated. Durvalumab, a monoclonal antibody directed against the programmed death ligand 1, has demonstrated significant activity in NSCLC, including increased progression-free survival rates after chemoradiation for unresectable stage III disease, with a favourable safety profile. Clinical trials, including phase III studies, are ongoing as monotherapy and in combination with chemotherapy, radiotherapy and other immunotherapies, such as the anti-cytotoxic T-lymphocyte antigen 4 drug tremelimumab, in diverse stages of the disease.

scholarly journals Vitamin C—An Adjunctive Therapy for Respiratory Infection, Sepsis and COVID-19

2020 ◽  
Author(s):  
Patrick Holford ◽  
Anitra Carr ◽  
Thomas H. Jovic ◽  
Stephen R. Ali ◽  
Iain S. Whitaker ◽  
...  
Keyword(s):  
Vitamin C ◽  
Adjunctive Therapy ◽  
Respiratory Infections ◽  
Low Cost ◽  
Vitamin C Deficiency ◽  
Favourable Safety ◽  
Favourable Safety Profile ◽  
Hospital Stays ◽  
Anti Inflammatory ◽  
Intravenous Vitamin

There are limited proven therapies for the treatment of COVID-19. Vitamin C&rsquo;s antioxidant, anti-inflammatory and immunomodulating effects, make it a potential therapeutic candidate, both for the prevention and amelioration of COVID-19 infection, and as an adjunctive therapy in the critical care of COVID-19, supporting anti-inflammatory treatment. This literature review focuses on vitamin C deficiency in respiratory infections including COVID-19; the mechanism of action in infectious disease and adrenal function supporting the anti-inflammatory actions of glucocorticosteroids: its role in preventing and treating colds and pneumonia and its role in treating sepsis and COVID-19. The evidence to date indicates that oral vitamin C (2-8g/d) may reduce incidence and duration of respiratory infections and intravenous vitamin C (2-24g/d) has been shown to reduce mortality, Intensive Care Unit and hospital stays, time on mechanical ventilation in severe respiratory infections. Further trials are urgently warranted. Given the favourable safety profile and low cost of vitamin C, and frequency of vitamin C deficiency in respiratory infections it may be worthwhile testing patients&rsquo; vitamin C status and treating accordingly with intravenous use within ICUs and orally with doses between 2 and 8g/day in hospitalised and infected persons.

scholarly journals Radiochemical synthesis and evaluation in nonhuman primates of 3-[11C]methoxy-4-aminopyridine: a novel PET tracer for imaging potassium channels in the CNS

2020 ◽  
Author(s):  
Nicolas J. Guehl ◽  
Ramesh Neelamegam ◽  
Yu-Peng Zhou ◽  
Sung-Hyun Moon ◽  
Maeva Dhaynaut ◽  
...  
Keyword(s):  
Brain Injury ◽  
Nonhuman Primates ◽  
Neurological Diseases ◽  
High Plasma ◽  
K Channel ◽  
Pet Tracer ◽  
Highly Sensitive ◽  
Focal Brain Injury ◽  
Pet Radiotracers ◽  
Imaging Properties

Demyelination, the loss of the protecting sheath of neurons, contributes to disability in many neurological diseases. In order to fully understand its role in different diseases and to monitor treatments aiming at reversing this process, it would be valuable to have PET radiotracers that can detect and quantify molecular changes involved in demyelination. Carbon-11 labeled radiotracers present the advantage of allowing for multiple scans on the same subject in the same day. Here, we describe [11C]3MeO4AP, a novel 11C-labeled version of the K+ channel tracer [18F]3F4AP, and characterize its imaging properties in two nonhuman primates including a monkey with a focal brain injury sustained during a surgical procedure three years prior to imaging. Our findings show that [11C]3MeO4AP is brain permeable, metabolically stable and has high plasma availability. When compared with [18F]3F4AP, [11C]3MeO4AP shows very high correlation in volumes of distribution (VT) confirming a common target. [11C]3MeO4AP shows slower washout than [18F]3F4AP suggesting stronger binding. Finally, similar to [18F]3F4AP, [11C]3MeO4AP is highly sensitive to the focal brain injury. All these features make it a promising radioligand for imaging demyelinated lesions.

scholarly journals Risks associated with oral deferiprone in the treatment of infratentorial superficial siderosis

2019 ◽  
Vol 267 (1) ◽  
pp. 239-243 ◽  
Author(s):  
Y. Sammaraiee ◽  
G. Banerjee ◽  
S. Farmer ◽  
B. Hylton ◽  
P. Cowley ◽  
...  
Keyword(s):  
Side Effects ◽  
Case Series ◽  
Iron Chelator ◽  
Superficial Siderosis ◽  
Neutropenic Sepsis ◽  
Favourable Safety ◽  
Favourable Safety Profile ◽  
Life Threatening ◽  
The Mean ◽  
Mean Time

Abstract Objective Deferiprone is an iron chelator that has recently been used to treat patients with infratentorial superficial siderosis (iSS). It is considered to have a generally favourable safety profile but concerns have been raised due to the risk of agranulocytosis. We aimed to evaluate the safety and tolerability of oral deferiprone as a treatment for patients with iSS. Methods We present a case series of 10 consecutive patients presenting with classical iSS treated with deferiprone. Results Ten patients were followed up for a mean period of 2.3 years (range 0.5–5.5 years). Four patients (40%) were withdrawn from treatment because of treatment-related side effects. The reasons for treatment discontinuation were neutropenic sepsis (n = 3) and fatigue (n = 1). In 2 out of the 3 cases of neutropenic sepsis, patients initially developed neutropenia without sepsis. The mean time to neutropenic sepsis following deferiprone was 1.2 years (range 0.3–2.5) with mean neutrophil count of 0.4 (range 0.3–0.5). Six patients (60%) reported no change in neurological function while on treatment, and four patients (40%) reported that their condition deteriorated. Conclusions Deferiprone was poorly tolerated, with 40% of patients withdrawing from treatment, most commonly due to neutropenic sepsis, after an average of 2 years on treatment. This study increases the number of reported cases of agranulocytosis in patients with iSS treated with deferiprone. Clinicians treating iSS patients with deferiprone should be aware that this drug has a potentially life-threatening side effect of neutropenic sepsis, and should ensure that appropriate haematological monitoring is in place.

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