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Topic Review
Disease-Modification in Neurodegenerative Disorders
The clinical failure rate for disease-modifying treatments (DMTs) that slow or stop disease progression has been nearly 100% for the major neurodegenerative disorders (NDDs), with many compounds failing in expensive and time-consuming phase 2 and 3 trials for lack of efficacy. However, as our understanding of NDDs is improving, there is a rise in potentially disease-modifying treatments being brought to the clinic. Further increasing the rational use of mechanistic biomarkers in early phase trials for these (targeted) therapies can increase R&D productivity with a quick win/fast fail approach in an area that has seen a nearly 100% failure rate to date.
  • 952
  • 15 Mar 2021
Topic Review
Trimethylamine N-Oxide in Normal Cognitive Aging
Trimethylamine-N-oxide (TMAO), a gut microbiota-derived metabolite from dietary precursors, might emerge as a promising biomarker of cognitive dysfunction within the context of brain aging and NCD. TMAO may increase among older adults, Alzheimer’s disease patients, and individuals with cognitive sequelae of stroke. Higher circulating TMAO would make them more vulnerable to age- and NCD-related cognitive decline, via mechanisms such as promoting neuroinflammation and oxidative stress, and reducing synaptic plasticity and function.
  • 951
  • 21 Oct 2022
Topic Review
Stress, Anxiety and Depression
Stress, anxiety and depressive disorders are often characterized by the activation of the stress axis, which results in similar symptoms at some point in these disorders. These disorders are closely related to each other—they occur simultaneously or follow one another. The diagnosis of stress, anxiety and depression is not a perfect procedure currently—it is based on patient observation and an interview with the patient and their family. There are no laboratory tests that would dispel the doubts of the doctor making the diagnosis and allow the appropriate treatment to be implemented as soon as possible. Therefore, this study will review the components of saliva that could be helpful in the quick diagnosis of stress, anxiety and/or depression. Such potential salivary biomarkers could also be useful in monitoring the effectiveness of pharmacological treatment prescribed by a psychiatrist. The following are promising salivary biomarkers of stress, anxiety or depression: cortisol, immunoglobulin A (sIgA), lysozyme, melatonin, α-amylase (sAA), chromogranin A (CgA) and fibroblast growth factor 2 (FGF-2). 
  • 948
  • 16 Apr 2021
Topic Review
Autophagy and Neurodegenerative Diseases
The word autophagy was introduced in late 1963 by the biochemist Christian de Duve [18] and defines a self-degradative cellular pathway whose intent is to degrade and recycle cellular contents. Autophagy exists in three forms that are classified according to their mechanisms and cellular functions: macroautophagy, microautophagy, and chaperone-mediated autophagy (CMA). During microautophagy, the cytosolic material is wrapped and transported directly into the lumen of lysosomes. The main function of microautophagy (mA) is to control cell survival and organellar turnover upon nitrogen restriction. CMA has an important role in protein quality control (QC) and is responsible for degrading a specific subset of oxidized and damaged proteins. The selectivity of CMA is conferred by the existence of a specific pentapeptide motif (KFERQ), which is present in the amino acid sequences of all CMA substrates. Undoubtedly, the best-characterized and most prevalent form of autophagy in mammalian cells is macroautophagy (hereafter referred to as autophagy). Autophagy is responsible to capture a wide group of intracellular components, ranging from low-dimensional biological macromolecules to whole organelles, and bring them to the lysosomal compartment. Its physiological value rests on two main activities. On the one hand, autophagy acts as a QC mechanism that reshapes the cell, ensuring the removal of damaged proteins and organelles [27]. Selective forms of autophagy can specifically target mitochondria (mitophagy), the endoplasmic reticulum (ER; reticulophagy), peroxisomes (pexophagy), and lipid droplets (lipophagy).
  • 947
  • 16 Apr 2021
Topic Review
Treatment Resistance in Early Psychosis
Treatment resistance is prevalent in early intervention in psychosis services, and causes a significant burden for the individual. A wide range of variables are shown to contribute to treatment resistance in first episode psychosis (FEP). Heterogeneity in illness course and the complex, multidimensional nature of the concept of recovery calls for an evidence base to better inform practice at an individual level. Current gold standard treatments, adopting a ‘one-size fits all’ approach, may not be addressing the needs of many individuals.
  • 945
  • 09 Dec 2020
Topic Review
Corpus Callosotomy for Controlling Epileptic Spasms
Epileptic spasms (ESs) are a type of epileptic seizure characterized as brief muscle contractions with ictal polyphasic slow waves on an electroencephalogram and a main feature of West syndrome. Resection surgeries, including frontal/posterior disconnections and hemispherotomy, have been established for the treatment of medically intractable ES in patients with unilaterally localized epileptogenic regions. Corpus callosotomy (CC) has been mainly used to treat drop attacks, which are classified as generalized tonic or atonic seizures. However, CC has also been adopted for ES treatment. 
  • 943
  • 18 Jan 2022
Topic Review
Botulinumtoxin A for Post-herpetic neuralgia
Post-herpetic neuralgia (PHN) is a very painful neuropathic condition, which occurs after nerve injury (e.g., demyelination, loss of axons, small-fiber-degeneration, reorganization in the dorsal horn of the spinal cord, and neuroplastic central changes) due to herpes-zoster-virus infection and is defined as a local neuropathic pain lasting for more than three months following the initial acute zoster infection.  Adjunctive local BoNT A injection is a promising option for severe PHN, as a safe and effective therapy in long-term management for chronic neuropathic pain.
  • 941
  • 16 Jan 2022
Topic Review
Personalized Medicine in Parkinson’s Disease
Parkinson’s disease (PD) presents varying motor and non-motor features in each patient owing to their different backgrounds, such as age, gender, genetics, and environmental factors. Furthermore, in the advanced stages, troublesome symptoms vary between patients due to motor and non-motor complications. The treatment of PD has made great progress over recent decades and has directly contributed to an improvement in patients’ quality of life, especially through the progression of advanced treatment. Deep brain stimulation, radiofrequency, MR–guided focused ultrasound, gamma knife, levodopa-carbidopa intestinal gel, and apomorphine are now used in the clinical setting for this disease.
  • 939
  • 26 Jul 2021
Topic Review
Vitamin D Supplementation on Fatigue in Multiple Sclerosis
Multiple sclerosis (MS) is an autoimmune and inflammatory chronic disease of the central nervous system that constitutes one of the leading causes of disability among young adults. Multiple sclerosis can produce a variety of symptoms, such as fatigue, blurred vision, optic neuritis, weakness, dizziness, balance disturbances, cognitive decline, and problems with bladder control, as well as an increased risk of depression and anxiety. Fatigue is one of the most common and disabling symptoms and can be described as a subjective lack of physical and/or mental energy that interferes with usual activities. 
  • 934
  • 04 Jul 2023
Topic Review
Primary Lateral Sclerosis
Primary lateral sclerosis (PLS) is a rare neurodegenerative disorder which causes the selective deterioration of the upper motor neurons (UMNs), sparing the lower motor neuron (LMN) system. The clinical course is defined by a progressive motor disability due to muscle spasticity which typically involves lower extremities and bulbar muscles. Although classically considered a sporadic disease, some familiar cases and possible causative genes have been reported. Despite it having been recognized as a rare but distinct entity, whether it actually represents an extreme end of the motor neuron diseases continuum is still an open issue. The main knowledge gap is the lack of specific biomarkers to improve the clinical diagnostic accuracy. Indeed, the diagnostic imprecision, together with some uncertainty about overlap with UMN-predominant ALS and Hereditary Spastic Paraplegia (HSP), has become an obstacle to the development of specific therapeutic trials.
  • 931
  • 31 Jan 2024
Topic Review
Therapy for Post-Stroke Spasticity
ESWT is safe and free of undesirable side effects. The mechanism of action of ESWT on muscles affected by spasticity is still unknown. To date, no standard parameters of ESWT in post-stroke spasticity regarding intensity, frequency, location, and the number of sessions has been established.
  • 930
  • 24 Apr 2021
Topic Review
Clinical Neurophysiology and Genetics of Dystonia Diagnosis
Dystonia diagnosis is based on clinical examination performed by a neurologist with expertise in movement disorders. Clues that indicate the diagnosis of a movement disorder such as dystonia are dystonic movements, dystonic postures, and three additional physical signs (mirror dystonia, overflow dystonia, and geste antagonists/sensory tricks). Despite advances in research, there is no diagnostic test with a high level of accuracy for the dystonia diagnosis. Clinical neurophysiology and genetics might support the clinician in the diagnostic process. Neurophysiology played a role in untangling dystonia pathophysiology, demonstrating characteristic reduction in inhibition of central motor circuits and alterations in the somatosensory system. The neurophysiologic measure with the greatest evidence in identifying patients affected by dystonia is the somatosensory temporal discrimination threshold (STDT). Other parameters need further confirmations and more solid evidence to be considered as support for the dystonia diagnosis. Genetic testing should be guided by characteristics such as age at onset, body distribution, associated features, and coexistence of other movement disorders (parkinsonism, myoclonus, and other hyperkinesia). 
  • 924
  • 06 Sep 2022
Topic Review
Noninvasive Brain Stimulation for Neurorehabilitation in Post-Stroke Patients
Noninvasive brain stimulation (NIBS) is a popular neuromodulatory technology of rehabilitation focusing on the local cerebral cortex, which can improve clinical functions by regulating the excitability of corresponding neurons. Increasing evidence has been obtained from the clinical application of NIBS in post-stroke patients, especially repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS). With advances in neuronavigation technologies, functional near-infrared spectroscopy, and functional MRI, specific brain regions can be precisely located for stimulation, which also presents the possibility that neuromodulation in post-stroke rehabilitation evolving from a single target to multiple targets, circuits and even networks. It is essential to review the findings of current research, discuss future directions of NIBS application, and finally promote the use of NIBS in post-stroke rehabilitation.
  • 922
  • 06 Apr 2023
Topic Review
Insular Cortex and Neuropathic pain
The insular cortex is an important information integration center. Numerous imaging studies have documented increased activity of the insular cortex in the presence of neuropathic pain; however, the specific role of this region remains controversial. 
  • 921
  • 19 Mar 2021
Topic Review
Oligodendrocytes and Vitamin D Neuroprotection in Multiple Sclerosis
Multiple sclerosis (MS) is a complex neurological condition that involves both inflammatory demyelinating and neurodegenerative components. MS research and treatments have traditionally focused on immunomodulation, with less investigation of neuroprotection, and this holds true for the role of vitamin D in MS. Vitamin D plays an anti-inflammatory role in modulating the immune system in MS. More recently, researchers have begun investigating the potential neuroprotective role of vitamin D in MS, which may be important in remyelination and/or the prevention of demyelination. There is a growing body of research uncovering mechanistic role of vitamin D-mediated neuroprotection, including: enhancing oligodendrocyte lineage differentiation, enhancing neurotrophin expression, attenuating aberrant microglial and reactive astrocyte activation, stabilizing the BBB, and reducing oxidative stress. 1,25(OH)2D3 promotes stem cell proliferation and drives the differentiation of neural stem cells into oligodendrocytes, which carry out remyelination. 
  • 915
  • 24 Oct 2023
Topic Review
High-Throughput Screening for Neurodegenerative Diseases
Neurodegenerative diseases (NDDs) are incurable and debilitating conditions that result in progressive degeneration and/or death of nerve cells in the central nervous system (CNS). High-throughput screening (HTS) has increasingly been used for novel drug discovery in the field of pharmaceutics replacing the traditional “trial and error” approach to identify therapeutic targets and validate biological effects. HTS involves assaying and screening a large number of biological effectors and modulators against designated and exclusive targets.
  • 912
  • 20 Jun 2023
Topic Review
Methods of Muscle Tone Diagnosis
“Muscle tone” is a clinically important and widely used term and palpation is a crucial skill for its diagnosis. However, the term is defined rather vaguely, and palpation is not measurable objectively. Therefore, several methods have been developed to measure muscle tone objectively, in terms of biomechanical properties of the muscle. 
  • 912
  • 29 Aug 2023
Topic Review
Substrate Selection in Neurodegenerative Diseases
Neurodegenerative diseases express multiple clinical phenotypes. A diversity of clinical phenotypes has been attributed to the ability of amyloidogenic proteins  to acquire multiple, self-replicating states referred to as strains. This article put forward a new hypothesis referred to as substrate selection hypothesis, according to which individual strains selectively recruit protein isoforms with a subset of posttranslational modifications that fit into strain-specific structures. As a result of selective recruitment, strain-specific patterns of posttranslational modifications are formed, giving rise to unique disease phenotypes.
  • 909
  • 24 Feb 2021
Topic Review
Neurofeedback and Neuromodulation
Neurofeedback is a non-invasive therapeutic approach that has gained traction in recent years, showing promising results for various neurological and psychiatric conditions. It involves real-time monitoring of brain activity, allowing individuals to gain control over their own brainwaves and improve cognitive performance or alleviate symptoms. The use of electroencephalography (EEG), such as brain–computer interface (BCI), transcranial direct current stimulation (tDCS), and transcranial magnetic stimulation (TMS), has been instrumental in developing neurofeedback techniques.
  • 905
  • 10 Aug 2023
Topic Review
Optical Coherence Tomography in Multiple Sclerosis
Multiple sclerosis (MS) is an inflammatory and neurodegenerative, potentially disabling disease of the central nervous system. OCT (Optical Coherence Tomography) and OCT-A (Optical Coherence Tomography with Angiography) are imaging techniques for the retina and choroid that are used in the diagnosis and monitoring of ophthalmological conditions. 
  • 900
  • 10 Aug 2022
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