Pathophysiological Mechanisms

Author(s):  
Erwin B. Montgomery

Pathophysiology is central to neuroscience and psychiatry for a number of reasons. Indeed, nearly every inference to normal function of the nervous system is derived from notions of pathophysiology. Understanding DBS’s mechanisms of action—a therapeutic mechanism, particularly—greatly depends on the prior informing conception of pathophysiology. Several current theories of pathophysiology are critically reviewed such as the GPi Rate, high beta oscillations, excessive bursting and hypersynchronization theories. A novel theory offered that introduces the concept of the basal ganglia-thalamic-cortical system as a network of loosely coupled nonlinear polysynaptic reentrant oscillators.

2021 ◽  
Vol 11 (5) ◽  
pp. 535
Author(s):  
Davide Sattin ◽  
Francesca Giulia Magnani ◽  
Laura Bartesaghi ◽  
Milena Caputo ◽  
Andrea Veronica Fittipaldo ◽  
...  

The amount of knowledge on human consciousness has created a multitude of viewpoints and it is difficult to compare and synthesize all the recent scientific perspectives. Indeed, there are many definitions of consciousness and multiple approaches to study the neural correlates of consciousness (NCC). Therefore, the main aim of this article is to collect data on the various theories of consciousness published between 2007–2017 and to synthesize them to provide a general overview of this topic. To describe each theory, we developed a thematic grid called the dimensional model, which qualitatively and quantitatively analyzes how each article, related to one specific theory, debates/analyzes a specific issue. Among the 1130 articles assessed, 85 full texts were included in the prefinal step. Finally, this scoping review analyzed 68 articles that described 29 theories of consciousness. We found heterogeneous perspectives in the theories analyzed. Those with the highest grade of variability are as follows: subjectivity, NCC, and the consciousness/cognitive function. Among sub-cortical structures, thalamus, basal ganglia, and the hippocampus were the most indicated, whereas the cingulate, prefrontal, and temporal areas were the most reported for cortical ones also including the thalamo-cortical system. Moreover, we found several definitions of consciousness and 21 new sub-classifications.


2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii330-iii331
Author(s):  
Hirokazu Takami ◽  
Koichi Ichimura ◽  
Kohei Fukuoka ◽  
Akitake Mukasa ◽  
Nobuhito Saito ◽  
...  

Abstract BACKGROUND We integrated clinical, histopathological, and molecular data of central nervous system germ cell tumors to provide insights into their management. METHODS Data from the Intracranial Germ Cell Tumor Genome Analysis Consortium were reviewed. A total of 190 cases were classified as primary GCTs based on central pathological reviews. RESULTS All but one of the cases that were bifocal (neurohypophysis and pineal glands) and cases with multiple lesions including neurohypophysis or pineal gland were germinomas (34 of 35). Age was significantly higher in patients with germinoma than other histologies. Comparison between tumor marker and histopathological diagnoses showed that 18.2% of histopathologically diagnosed germinomas were marker-positive and 6.1% of non-germinomatous GCTs were marker-negative, suggesting a limitation in the utility of markers or histopathology alone using small specimens for diagnosis. Comparison between local and central histopathological diagnoses revealed a discordance of 12.7%. Discordance was significantly less frequent in biopsy cases, implying difficulty in detecting all histopathological components of heterogeneous GCTs. Germinomas at the typical sites (neurohypophysis or pineal gland) showed a better PFS than those at atypical sites (p=0.03). A molecular-clinical association study revealed frequent MAPK pathway mutations in males (51.4 vs 14.3 %, p=0.007), and PI3K/mTOR pathway mutations in basal ganglia cases (p=0.004). Basal ganglia cases also had frequent chromosomal losses. Some chromosomal aberrations (2q, 8q gain, 5q, 9p/q, 13q, 15q loss) showed potential prognostic significance. CONCLUSIONS These in-depth findings of this study regarding the clinical and molecular heterogeneity will increase our understanding of the pathogenesis of this enigmatic tumor.


2012 ◽  
Vol 2012 ◽  
pp. 1-4 ◽  
Author(s):  
Layal Safadieh ◽  
Rana Sharara-Chami ◽  
Omar Dabbagh

Streptococcus pneumoniaeis a common cause of bacterial meningitis, frequently resulting in severe neurological impairment. A seven-month-old child presenting withStreptococcus pneumoniaemeningoencephalitis developed right basal ganglia and hypothalamic infarctions. Daily episodes of agitation, hypertension, tachycardia, diaphoresis, hyperthermia, and decerebrate posturing were observed. The diagnosis ofparoxysmal autonomic instability with dystoniawas established. The patient responded to clonidine, baclofen, and benzodiazepines. Although this entity has been reported in association with traumatic brain injury, and as a sequel to some nervous system infections, this is the first case, to our knowledge, associated with pneumococcal meningoencephalitis.


Author(s):  
J. Eric Ahlskog

As a prelude to the treatment chapters that follow, we need to define and describe the types of problems and symptoms encountered in DLB and PDD. The clinical picture can be quite varied: problems encountered by one person may be quite different from those encountered by another person, and symptoms that are problematic in one individual may be minimal in another. In these disorders, the Lewy neurodegenerative process potentially affects certain nervous system regions but spares others. Affected areas include thinking and memory circuits, as well as movement (motor) function and the autonomic nervous system, which regulates primary functions such as bladder, bowel, and blood pressure control. Many other brain regions, by contrast, are spared or minimally involved, such as vision and sensation. The brain and spinal cord constitute the central nervous system. The interface between the brain and spinal cord is by way of the brain stem, as shown in Figure 4.1. Thought, memory, and reasoning are primarily organized in the thick layers of cortex overlying lower brain levels. Volitional movements, such as writing, throwing, or kicking, also emanate from the cortex and integrate with circuits just below, including those in the basal ganglia, shown in Figure 4.2. The basal ganglia includes the striatum, globus pallidus, subthalamic nucleus, and substantia nigra, as illustrated in Figure 4.2. Movement information is integrated and modulated in these basal ganglia nuclei and then transmitted down the brain stem to the spinal cord. At spinal cord levels the correct sequence of muscle activation that has been programmed is accomplished. Activated nerves from appropriate regions of the spinal cord relay the signals to the proper muscles. Sensory information from the periphery (limbs) travels in the opposite direction. How are these signals transmitted? Brain cells called neurons have long, wire-like extensions that interface with other neurons, effectively making up circuits that are slightly similar to computer circuits; this is illustrated in Figure 4.3. At the end of these wire-like extensions are tiny enlargements (terminals) that contain specific biological chemicals called neurotransmitters. Neurotransmitters are released when the electrical signal travels down that neuron to the end of that wire-like process.


The Neuron ◽  
2015 ◽  
pp. 353-386
Author(s):  
Irwin B. Levitan ◽  
Leonard K. Kaczmarek

Neural development requires the participation of growth factors that regulate neuronal determination, proliferation, migration, and differentiation. Molecular genetic approaches using Drosophila, as well as other creatures whose genetics is well understood, have provided insights into the mechanisms of action of some of these developmental factors. Other factors are soluble and are secreted by nearby cells or other neurons. These include neurotrophins such as NGF and BDNF, cytokines such as CNTF, as well as GDNF and steroid hormones. Current research aims to identify key growth factors required for producing different types of neurons, and different patterns of transcription factor activated by different combinations of these factors. This knowledge may eventually allow medical therapies to convert a stem cell into a sympathetic neuron, a motor neuron, or any one of the thousands of other types of neurons that make up a mature nervous system.


2012 ◽  
Vol 58 ◽  
pp. 203-228 ◽  
Author(s):  
Niall Quinn ◽  
John Rothwell ◽  
Peter Jenner

David Marsden was the most outstanding UK clinical neuroscientist of his generation, making key discoveries in the neurophysiology, neurochemistry and clinical aspects of diseases of the basal ganglia, and their normal function. His legacies are the establishment, with Stanley Fahn in the USA, of movement disorders as a subspecialty within neurology, of the international Movement Disorder Society, and of the journal Movement Disorders ; his ex-students and fellows around the globe; and his research and teaching output embodied in his extraordinarily prolific publication record of more than 1360 papers, books and chapters, culminating in the posthumous completion and publication in December 2011 of Marsden’s book of movement disorders , a project he had started in 1984. All of these were achieved through the combination of his intellect and drive, his communication skills, and his forceful and charismatic personality.


2019 ◽  
Vol 21 (12) ◽  
pp. 1565-1577 ◽  
Author(s):  
Hirokazu Takami ◽  
Kohei Fukuoka ◽  
Shintaro Fukushima ◽  
Taishi Nakamura ◽  
Akitake Mukasa ◽  
...  

Abstract Background We integrated clinical, histopathological, and molecular data of central nervous system germ cell tumors to provide insights into their management. Methods Data from the Intracranial Germ Cell Tumor Genome Analysis (iGCT) Consortium were reviewed. A total of 190 cases were classified as primary germ cell tumors (GCTs) based on central pathological reviews. Results All but one of the cases that were bifocal (neurohypophysis and pineal glands) and cases with multiple lesions including neurohypophysis or pineal gland were germinomas (34 of 35). Age was significantly higher in patients with germinoma than other histologies. Comparison between tumor marker and histopathological diagnoses showed that 18.2% of histopathologically diagnosed germinomas were marker positive and 6.1% of non-germinomatous GCTs were marker negative, suggesting a limitation in the utility of markers or histopathology alone using small specimens for diagnosis. Comparison between local and central histopathological diagnoses revealed a discordance of 12.7%. Discordance was significantly less frequent in biopsy cases, implying difficulty in detecting all histopathological components of heterogeneous GCTs. Germinomas at the typical sites (neurohypophysis or pineal gland) showed a better progression-free survival than those at atypical sites (P = 0.03). A molecular clinical association study revealed frequent mitogen-activated protein kinase (MAPK) pathway mutations in males (51.4% vs 14.3%, P = 0.007), and phosphatidylinositol-3 kinase/mammalian target of rapamycin (PI3K/mTOR) pathway mutations in basal ganglia cases (P = 0.004). Basal ganglia cases also had frequent chromosomal losses. Some chromosomal aberrations (2q, 8q gain, 5q, 9p/q, 13q, 15q loss) showed potential prognostic significance. Conclusions The in-depth findings of this study regarding clinical and molecular heterogeneity will increase our understanding of the pathogenesis of this enigmatic tumor.


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