One in a Million: A Case Report of Stiff Person Syndrome

Stiff person syndrome (SPS) is a rare autoimmune disease caused by lack of inhibition to excitatory neurotransmitters in the central nervous system (CNS) leading to inappropriate motor unit firing. The pathophysiology is incompletely understood; however, high titers of antiglutamic acid decarboxylase antibody (anti-GAD Ab) are strongly associated with this disease. We present a 50-year-old woman with a history of ongoing gait and balance issues for 5 years with multiple negative workups. She recently had an acute exacerbation which left her bedbound, unable to move her legs or turn from side to side. After a negative workup at an outside hospital, the patient was discharged to a subacute rehabilitation facility. She then presented to our institution due to worsening of her condition and was ultimately diagnosed with SPS which was successfully treated. We review the case presentation and treatment options in the context of a severe disabling disease presentation.

Antinociceptive activities of a novel diarylpentanoid analogue, 2-benzoyl-6-(3-bromo-4-hydroxybenzylidene)cyclohexen-1-ol, and its possible mechanisms of action in mice

A novel synthetic compound from the 2-benzoyl-6-benzylidenecyclohexanone analogue, namely 2-benzoyl-6-(3-bromo-4-hydroxybenzylidene)cyclohexen-1-ol (BBHC), showed pronounced nitric oxide inhibition in IFN-γ/LPS-induced RAW 264.7 cells. Based on this previous finding, our present study aimed to investigate the antinociceptive effects of BBHC via chemical and thermal stimuli in vivo. The investigation of the antinociceptive activity of BBHC (0.1, 0.3, 1.0 and 3.0 mg/kg, i.p.) was initiated with 3 preliminary screening tests, then BBHC was subjected to investigate its possible involvement with excitatory neurotransmitters and opioid receptors. The potential acute toxicity of BBHC administration was also studied. Administration of BBHC significantly inhibited acetic acid-induced abdominal constrictions, formalin-induced paw licking activity and developed notable increment in the latency time. BBHC’s ability to suppress capsaicin- and glutamate-induced paw licking activities, as well as to antagonise the effect of naloxone, had indicated the possible involvement of its antinociception with TRPV1, glutamate and opioid receptors, respectively. The antinociceptive activities of BBHC was not related to any sedative action and no evidence of acute toxic effect was detected. The present study showed that BBHC possessed significant peripheral and central antinociceptive activities via chemical- and thermal-induced nociceptive murine models without any locomotor alteration and acute toxicity.

Modeling of human reaction selection following the arrival of an event in the brain

This work proposes a mathematical model about how a reaction is created in the human brain in responseto a particular incoming Information/Event using quantum mechanics and more precisely path integrals theory.The set of action potentials created in a particular neuron N2 is a result of temporal and spatial summationof the signals coming from different neighboring neurons Nx with different dendrite-paths. Each dendritepathof N2 is assumed to be determined by its respective synapse with its neurotransmitters and therefore tohave its particular action S due to its respective neurotransmitters types (excitatory or inhibitory) and etc. Anexternal incoming signal information being initially modulated by recepetor neurons (in eyes, ears...) travelsthrough the neighboring neurons that are linked to the excited receptor neurons. A potential reaction responsesare subsequently created thanks to a final deformed signal in the motor neurons by all the correlated neuralpaths. The total deformation at each neuron is created by different incoming dendrite-paths and their structures(inhibitory or excitatory neurotransmitters and their type), and of course the existence or not of the signal andits frequency coming from each path. Using path Integrals theory, we compute the probability of existence ofthe signal-Information or the potential reaction to the incoming information at each neuron. In this paper wecompute how much the signal-Information has been distorted between two neighboring linked neural pointsincluding if it arrives or not to the neigboring neurons. We propose an Information entropy similar to Shannonone and we demonstrate that this entropy is equivalent to timespace curvature in the Brain.

Electrophysiological and Morphological Studies of SOD1 Transgenic Mice: An Animal Model of ALS

Amyotrophic lateral sclerosis (ALS) is a disease where upper and lower motor neurons die, and it is often associated with mutations of superoxide dismutase 1 (SOD1). We have used mouse models to compare physiologic and morphologic characteristics of cervical motor neurons in wild-type and mutant animals. Slices of the cervical spinal cord were prepared from old wild-type and mutant G93A and G85R mice, and intracellular recordings of membrane potential, resistance and responses to application of excitatory neurotransmitters were studied. Some motor neurons were injected with Lucifer Yellow for morphological analysis. There were no significant differences between membrane potential in the SOD1 mutants and aged wild-type mice, but membrane resistance was somewhat higher in the mutant motor neurons. Dendrites of the mutant motor neurons were not responsive to ionophoretic application of excitatory amino acids, although the cell body responded strongly. In Lucifer-filled cells, the dendrites were found to disappear. Mutant motor neurons were sometimes spontaneously active. Responses of mutant motor neurons to perfused glutamate with varying calcium concentrations in the Ringer’s solution were different from those of the wild-type cells.

Electroacupuncture at ST36 Improve the Gastric Motility by Affecting Neurotransmitters in the Enteric Nervous System in Type 2 Diabetic Rats

Electroacupuncture (EA) can effectively relieve hyperglycemia and gastric emptying disorders in diabetic gastroparesis (DGP). However, the effect of EA on type 2 diabetes mellitus (T2DM) gastroparesis and its mechanism in the enteric nervous system (ENS) are rarely studied. We investigated the therapeutic effect of EA at ST36 and its effect on the main inhibitory and excitatory neurotransmitters in the ENS in DGP rats. Male Sprague-Dawley (SD) rats were fed a high-fat diet for 2 weeks and injected with streptozotocin (STZ) at 35 mg/kg to induce T2DM. T2DM rats were divided into the diabetic mellitus (DM) group and the EA group. The control (CON) group comprised normal rats without any intervention. EA treatment was started 6 weeks after the induction of DM and continued for 5 weeks. The body weight and food intake of the rats were recorded every week. Blood glucose, insulin, glucose tolerance, gastric emptying, and antral motility were measured after treatment. The expression of protein gene product 9.5 (PGP9.5), neuronal nitric oxide synthase (nNOS), and choline acetyltransferase (ChAT) in gastric antrum were quantified by western blotting and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). The T2DM gastroparesis model was successfully established. EA treatment reduced the body weight, food intake, and blood glucose; improved glucose intolerance and insulin resistance; increased the gastric emptying rate, the mean antral pressure, and the amplitude of antral motility; and decreased the frequency of antral motility compared with those in the DM group. EA treatment increased the expression level of nNOS, ChAT, and PGP9.5 proteins, and nNOS and ChAT mRNA. The results suggested that EA at ST36 could ameliorate DGP, partly restore the damage to general neurons, and increase nNOS and ChAT in the gastric antrum. EA improved DGP partly via reducing the loss of inhibitory and excitatory neurotransmitters in the ENS.

Status Epilepticus During Recovery from General Anesthesia

Propofol is an anesthetic agent commonly used for sedation and induction and/or maintenance of general anesthesia and presents an inhibitory effect on the excitatory neurotransmitters through GABA receptors. Although propofol is an agent that can be used to treat status epilepticus because of its anticonvulsant property, it may cause epileptiform convulsions, as reported in the literature. In this case report, a young patient’s epileptiform convulsions after administering a single dose of propofol injection for general anesthesia are presented. Due to uncontrolled epilepsy episodes following extubation, the patient was taken to intensive care. The patient regained consciousness, and epileptic attacks were controlled on the 4th day of intensive, was taken to the neurology service. We consider that this case is noteworthy concerning the association between propofol and epilepsy in anesthesia. Thus, this study aimed to draw attention to propofol in patients with a history of epilepsy.

Reflex memory theory of acquired involuntary motor and sensory disorders

Background Explicit and implicit memories are conserved but flexible biological tools that nature uses to regulate the daily behaviors of human beings. An aberrant form of the implicit memory is presumed to exist and may be contributory to the pathophysiology of disorders such as tardive syndromes, phantom phenomena, flashback, posttraumatic stress disorders (PTSD), and related disorders. These disorders have posed significant clinical problems for both patients and physicians for centuries. All extant pathophysiological theories of these disorders have failed to provide basis for effective treatment. Objective The objective of this article is to propose an alternative pathophysiological theory that will hopefully lead to new treatment approaches. Methods The author sourced over 60 journal articles that treated topics on memory, and involuntary motor and sensory disorders, from open access journals using Google Scholar, and reviewed them and this helped in the formulation of this theory. Results From the reviews, the author thinks physical or chemical insult to the nervous system can cause defective circuit remodeling, leading to generation of a variant of implicit (automatic) memory, herein called “reflex memory” and this is encoded interoceptively to contribute to these phenomena states. Conclusion Acquired involuntary motor and sensory disorders are caused by defective circuit remodeling involving multiple neural mechanisms. Dysregulation of excitatory neurotransmitters, calcium overload, homeostatic failure, and neurotoxicity are implicated in the process. Sustained effects of these defective mechanisms are encoded interoceptively as abnormal memory in the neurons and the conscious manifestations are these disorders. Extant theories failed to recognize this possibility.

Sodium Transporters in Human Health and Disease

Sodium (Na+) electrochemical gradients established by Na+/K+ ATPase activity drives the transport of ions, minerals, and sugars in both excitable and non-excitable cells. Na+-dependent transporters can move these solutes in the same direction (cotransport) or in opposite directions (exchanger) across both the apical and basolateral plasma membranes of polarized epithelia. In addition to maintaining physiological homeostasis of these solutes, increases and decreases in sodium may also initiate, directly or indirectly, signaling cascades that regulate a variety of intracellular post-translational events. In this review, we will describe how the Na+/K+ ATPase maintains a Na+ gradient utilized by multiple sodium-dependent transport mechanisms to regulate glucose uptake, excitatory neurotransmitters, calcium signaling, acid-base balance, salt-wasting disorders, fluid volume, and magnesium transport. We will discuss how several Na+-dependent cotransporters and Na+-dependent exchangers have significant roles in human health and disease. Finally, we will discuss how each of these Na+-dependent transport mechanisms have either been shown or have the potential to use Na+ in a secondary role as a signaling molecule.

Antinociception mechanisms of action of cannabinoid-based medicine: an overview for anesthesiologists and pain physicians

Cannabinoid-based medications possess unique multimodal analgesic mechanisms of action, modulating diverse pain targets. Cannabinoids are classified based on their origin into three categories: endocannabinoids (present endogenously in human tissues), phytocannabinoids (plant derived) and synthetic cannabinoids (pharmaceutical). Cannabinoids exert an analgesic effect, peculiarly in hyperalgesia, neuropathic pain and inflammatory states. Endocannabinoids are released on demand from postsynaptic terminals and travels retrograde to stimulate cannabinoids receptors on presynaptic terminals, inhibiting the release of excitatory neurotransmitters. Cannabinoids (endogenous and phytocannabinoids) produce analgesia by interacting with cannabinoids receptors type 1 and 2 (CB1 and CB2), as well as putative non-CB1/CB2 receptors; G protein-coupled receptor 55, and transient receptor potential vanilloid type-1. Moreover, they modulate multiple peripheral, spinal and supraspinal nociception pathways. Cannabinoids-opioids cross-modulation and synergy contribute significantly to tolerance and antinociceptive effects of cannabinoids. This narrative review evaluates cannabinoids’ diverse mechanisms of action as it pertains to nociception modulation relevant to the practice of anesthesiologists and pain medicine physicians.