Treatment Of Neurological Complications Research Articles

The importance of monitoring cerebral oxygenation in non brain injured patients.

Over the past few years, the use of non-invasive neuromonitoring in non-brain injured patients has increased, as a result of the recognition that many of these patients are at risk of brain injury in a wide number of clinical scenarios and therefore may benefit from its application which allows interventions to prevent injury and improve outcome. Among these, are post cardiac arrest syndrome, sepsis, liver failure, acute respiratory failure, and the perioperative settings where in the absence of a primary brain injury, certain groups of patients have high risk of neurological complications. While there are many neuromonitoring modalities utilized in brain injured patients, the majority of those are either invasive such as intracranial pressure monitoring, require special skill such as transcranial Doppler ultrasonography, or intermittent such as pupillometry and therefore unable to provide continuous monitoring. Cerebral oximetry using Near infrared Spectroscopy, is a simple non invasive continuous measure of cerebral oxygenation that has been shown to be useful in preventing cerebral hypoxemia both within the intensive care unit and the perioperative settings. At present, current recommendations for standard monitoring during anesthesia or in the general intensive care concentrate mainly on hemodynamic and respiratory monitoring without specific indications regarding the brain, and in particular, brain oximetry. The aim of this manuscript is to provide an up-to-date overview of the pathophysiology and applications of cerebral oxygenation in non brain injured patients as part of non-invasive multimodal neuromonitoring in the early identification and treatment of neurological complications in this population.

Neurological complications of SARS-CoV-2 infection

SARS-CoV-2 virus was first identified in 2019 in Wuhan (China) and is responsible for the ongoing COVID-19 pandemic. Although the virus causes mild, transient symptoms of an upper respiratory tract infection in most cases, it can also lead to severe pneumonia, respiratory failure and/or death. Approximately 85% of patients experience central and peripheral neurological symptoms. In the acute phase of the disease, ischaemic strokes, intracranial haemorrhages, meningitis and encephalitis, acute demyelinating diseases and acute inflammatory polyneuropathies may occur. However, mild neurological symptoms that can persist for months and significantly affect daily functioning are much more common. These include headache and dizziness, olfactory and gustatory dysfunction, mild cognitive disturbances, as well as depressive, anxiety, and sleep disorders. Some of them are encompassed by popular terms “post-covid syndrome” and “brain fog.” The pathogenesis of neurological complications of SARS-CoV-2 infection is still not fully understood; overproduction of cytokines induced by viral infection may be of great importance. There is no causal treatment, while symptomatic treatment is of limited effectiveness. Primary prevention in the form of SARS-CoV-2 vaccinations is of great importance. In the following review, we would like to present the current knowledge on epidemiology, pathology, pathogenesis and treatment of neurological complications after SARS-CoV-2 infection. Further multi-centre, large-scale clinical studies are necessary to identify the exact pathogenetic mechanisms.

Application of Sygen® in Diabetic Peripheral Neuropathies—A Review of Biological Interactions

This study investigates the role of Sygen® in diabetic peripheral neuropathy, a severe disease that affects the peripheral nervous system in diabetic individuals. This disorder often impacts the lower limbs, causing significant discomfort and, if left untreated, progresses into more serious conditions involving chronic ulcers and even amputation in many cases. Although there are management strategies available, peripheral neuropathies are difficult to treat as they often present multiple causes, especially due to metabolic dysfunction in diabetic individuals. Gangliosides, however, have long been studied and appreciated for their role in neurological diseases. The monosialotetrahexosylganglioside (GM1) ganglioside, popularly known as Sygen, provides beneficial effects such as enhanced neuritic sprouting, neurotrophism, neuroprotection, anti-apoptosis, and anti-excitotoxic activity, being particularly useful in the treatment of neurological complications that arise from diabetes. This product mimics the roles displayed by neurotrophins, improving neuronal function and immunomodulation by attenuating exacerbated inflammation in neurons. Furthermore, Sygen assists in axonal stabilization and keeps nodal and paranodal regions of myelin fibers organized. This maintains an adequate propagation of action potentials and restores standard peripheral nerve function. Given the multifactorial nature of this complicated disorder, medical practitioners must carefully screen the patient to avoid confusion and misdiagnosis. There are several studies analyzing the role of Sygen in neurological disorders. However, the medical literature still needs more robust investigations such as randomized clinical trials regarding the administration of this compound for diabetic peripheral neuropathies, specifically.

Neurologic Complications of Immune Checkpoint Inhibitors

The clinical use of cancer immunotherapy with immune checkpoint inhibitors has transformed the management of cancer and added another effective treatment option for different types of malignancies. The blockade of immune checkpoint pathways triggers an enhanced immune response leading to cancer regression but may also lead to autoimmune toxicities or immune-related adverse events, which may involve skin, endocrine, respiratory, gastrointestinal or neurologic manifestations. Clinically relevant neurologic complications involving the central and/or peripheral nervous system affect up to 1% of patients treated with immune checkpoint inhibitors and may be associated with significant morbidity and mortality. Common neurologic complications include aseptic meningitis and encephalitis, hypophysitis, myasthenia, myositis and neuropathies. Neurologic immune-related adverse events after immune checkpoint inhibition should be distinguished from cancer progression or other complications of cancer therapy (e.g. infections). The treatment of neurologic complications may include holding or withdrawing cancer immunotherapy, anti-inflammatory and immunosuppressive therapies with corticosteroids and steroid-sparing agents, immunomodulation with intravenous immune globulin or plasmapheresis and symptomatic treatment (e.g. antiepileptic medications, pain medications).

Treatment of neurological complications in patients with type 2 diabetes mellitus at the stage ofrehabilitation after COVID-19

Although the predominant clinical manifestation of COVID-19 is a respiratory disease, various neurological symptoms are increasingly being diagnosed, in particular, diabetic polyneuropathy is diagnosed in most patients with diabetes, affecting large and small nerve fibers. Drugs that are traditionally used for neuropathic pain (tricyclic antidepressants, gabapentinoids, etc.), despite their positive effect in eliminating the symptoms of polyneuropathy, often cause side effects and do not impact nerve regeneration. Over the last decade, a group of nucleotides has been used quite actively. Additional information on the effects of this group of drugs was accumulated and there is a gradual transformation, including their compositions. Thus, recently the attention of researchers has been devoted to the study of the effectiveness of the combination of uridine, choline, vitamins B1, B6, B12, and folic acid, which is characterized by a fairly high safety profile and regenerative potential. The review highlights the mechanisms of action and results of clinical use of this combination. Uridine monophosphate, B vitamins, folic acid are involved in metabolic processes, enhancing nerve regeneration. This contributes to the development of indirect (secondary) analgesic effect. In addition, the data of new studies indicate the ability of uridine monophosphate derivatives to impact purinergic P2Y receptors, which causes a direct analgesic and direct regenerative effect. Studies have demonstrated the clinical efficacy of this combination in the main types of peripheral neuropathic pain. The combination did not cause side effects and was well tolerated. There was a reduction or complete withdrawal of concomitant analgesics against the background of improving the quality of life of patients. The combination of uridine, choline, vitamin B1, vitamin B6, vitamin B12, and folic acid is a very effective addition to the standard therapy of peripheral neuropathic pain of various genesis and rehabilitation after COVID-19.

Narrative Review of Neurologic Complications in Adults on ECMO: Prevalence, Risks, Outcomes, and Prevention Strategies.

Extracorporeal membrane oxygenation (ECMO), a life-saving technique for patients with severe respiratory and cardiac diseases, is being increasingly utilized worldwide, particularly during the coronavirus disease 2019(COVID-19) pandemic, and there has been a sharp increase in the implementation of ECMO. However, due to the presence of various complications, the survival rate of patients undergoing ECMO remains low. Among the complications, the neurologic morbidity significantly associated with venoarterial and venovenous ECMO has received increasing attention. Generally, failure to recognize neurologic injury in time is reportedly associated with poor outcomes in patients on ECMO. Currently, multimodal monitoring is increasingly utilized in patients with devastating neurologic injuries and has been advocated as an important approach for early diagnosis. Here, we highlight the prevalence and outcomes, risk factors, current monitoring technologies, prevention, and treatment of neurologic complications in adult patients on ECMO. We believe that an improved understanding of neurologic complications presumably offers promising therapeutic solutions to prevent and treat neurologic morbidity.

A unique case of Miller Fisher-Guillain-Barr\xe9 overlap syndrome in a liver transplant recipient

Guillain-Barré syndrome (GBS) is an ascending demyelinating polyneuropathy often associated with recent infection. Miller Fisher syndrome represents a variant with predominant facial and cranial nerve involvement, although Miller Fisher and Guillain-Barré overlap syndromes can occur. Guillain-Barré spectrum syndromes have been thought to be rare among solid organ transplant recipients. We describe an immunocompromised patient with a liver transplant who presented with ophthalmoplegia and bulbar deficits. His symptoms rapidly progressed to a state of descending paralysis involving the diaphragm; he then developed acute respiratory failure and eventually developed quadriparesis. Electromyography and a nerve conduction study demonstrated a severe sensorimotor axonal polyneuropathy consistent with Miller Fisher variant Guillain-Barré syndrome. Despite several negative nasopharyngeal swabs for COVID-19 polymerase chain reaction, a serology for SARS-CoV-2 IgG was positive. He was diagnosed with Miller Fisher-Guillain-Barré overlap syndrome with rapid recovery following treatment with plasma exchange. Although Guillain-Barré is a rare complication in solid organ transplant recipients, this case highlights the importance of rapid diagnosis and treatment of neurologic complications in transplant patients. Furthermore, it demonstrates a possible case of neurological complications from COVID-19 infection.

NEUROLOGICAL COMPLICATIONS OF COVID-19: REVIEW OF LITERATURE AND OWN EXPERIENCE

According to the literature, the main neurological complications of COVID-19 are hyposmia, hypogeia, headache, dizziness, myalgia, and severe neurological syndromes like encephalopathy, stroke, and coma. The mechanisms of neurological complications of the acute period are direct viral damage, hypoxic damage, and immune damage due to the activation of inflammation, including autoantibodies. After the end of the acute phase of the disease, neurological complications in the form of asthenic syndrome, vascular syndrome, exacerbation of chronic diseases (deterioration of cognitive and communication functions in patients with autism, schizophrenia, exacerbation of autoimmune neurological diseases, aggravation of the condition of patients with tics, increased frequency of epileptic seizures in adults and children, resumption of epileptic seizures in patients who were previously in stable remission, the debut of epileptic seizures). These disorders are based on the following mechanisms: neuroinflammation, activation of pro-inflammatory cytokines (IL-1, -2, -6, -8, -10, -17, -18, CXCL10, CCL2), formation of autoantibodies, increased permeability of the blood-brain barrier, mitochondrial dysfunction, adrenal and thyroid dysfunction, venous dyscirculation. In the treatment of neurological complications after a COVID-19 infection, it is advisable to use anti-inflammatory therapy, mitochondrial therapy (including the technique of intermittent hypoxic-hyperoxic therapy), detoxication, correction of hormonal status (primarily the state of the adrenal glands and thyroid gland), vasoactive therapy, and symptomatic therapy.

Erratum: The etiology, diagnosis, and treatment of neurological complications in Behçet disease and its related disorder Sweet disease

Erratum: The etiology, diagnosis, and treatment of neurological complications in Behçet disease and its related disorder Sweet disease

Неврологические нежелательные явления антипсихотической терапии

Aim of study: analyze recent publications, related to the incidence, clinical signs and treatment of antipsychotic-induced movement disorders. Material and methods : articles published in the last 10 years were searched in Scopus, Pubmed and Cochrane Library using following keywords: neurological side-effects, dyskinesia, antipsychotics. Results: current review summarizes the data on epidemiology, diagnosis, and treatment of neurological complications of antipsychotics were found. Provides information on risk factors and clinical features of parkinsonism, dystonia and tardive dyskinesia, as well as possible treatment options. Conclusion: early differential diagnosis of neurological complications and taking into account risk factors will reduce frequency and increase compliance.

The etiology, diagnosis, and treatment of neurological complications in Behçet disease and its related disorder Sweet disease

Behçet disease, and its related disorder Sweet disease, are multisystem inflammatory conditions characterized by muco-cutaneous symptoms. When neuropsychiatric symptoms appear, the two conditions are referred to as neuro-Behçet disease and neuro-Sweet disease. While diagnosing these conditions according to their diagnostic criteria, muco-cutaneous symptoms must be observed; however, neuropsychiatric symptoms may precede muco-cutaneous symptoms. In these conditions the dysregulation of cytokines, following the onset of oral muco-cutaneous bacterial infection, may induce an abnormal chemotaxis of neutrophils causing ectopic encephalitis and meningitis. Thus, an initial treatment targeting neutrophils should be considered based on the diagnosis of neuro-neutrophilic disease when symptoms indicating neutrophil hyperactivity are observed, even without muco-cutaneous symptoms. In addition to human leukocyte antigen-B51 and -A26, genome-wide association analyses have identified new susceptibility loci on the genes of various immunological factors in Behçet disease. These findings may help elucidate disease pathogenesis and assist the development of diagnostic modalities and therapeutic agents for neuro-neutrophilic disease.

Diagnostics and treatment of postoperative neuropathies of the trigeminal nerve in its bruises and stretching

The objective: to study the dynamics of changes in electrophysiological indices of soft tissues innervated by II and III branches of the trigeminal nerve with its bruises and stretching, which arise in patients after surgical remove of tumors and tumor like jaw formations, and also determine the possibility of using the hardware software complex «DIN-1» for the treatment of these neuropathies. Patients and methods. a survey and treatment of neurological complications in 180 patients after surgical remove of tumors and tumor-like formations of the upper and lower jaws was performed.Results. based on the survey, we found that the determination of electrophysiological indices of soft tissues innervated by II and III branches of the trigeminal nerve in cases after performing operations to remove benign neoplasms of the jaws is not only a diagnostic criterion for the severity of damage to the trigeminal nerve in the surgical wound, but also can serve as a prognostic criterion, which indicates the timing of recovery of the nerve.Conclusions. The use of hardware-software complex «DIN-1» in the treatment allowed to reduce the treatment of all patients with neuropathies caused by bruises of the second and third branches of the trigeminal nerve by a factor of 2, and by 1,5 times the duration of treatment of patients with neuropathies caused by their stretching.

Cerebral neurological complications in patients with thermal injury

Relevance. Treatment of patients with severe thermal injury includes therapy comorbidities and complications, among which the special role played by the central nervous system. Their development is largely determines the weighting of the condition worsens the prognosis, as well as leading the timing of recovery. For burn disease may be accompanied by the development of the cerebral neurological complications, such as burn encephalopathy, acute violation of cerebral circulation, secondary purulent meningitis. Intention – identify the main pathogenetic mechanisms of neurologic complications and their correction have burned. Methods Review and analysis of literature data on neurological complications from burned and their treatment options. Results and Discussion. In the genesis of neurological disorders in the burned main role constitute the hemodynamic, electrolyte disorders, violations, breach the blood-brain barrier in the face of intoxication. Develops complex disorders, which can result in secondary purulent meningitis and meningoencephalitis. A comprehensive treatment, including surgical restoration of the skin integument, infusion therapy, antibiotics, drugs neuroprotektors stimulants avoids a number of severe complications. Conclusion. Timely pathogenetically justified treatment of neurological complications in burned, carried out within the framework of the integrated therapy of burn disease is essential, because such an approach contributes to the best possible outcomes.

Pituitary Adenlylate Cyclase Activating Peptide Protects Adult Neural Stem Cells from a Hypoglycaemic milieu.

Hypoglycaemia is a common side-effect of glucose-lowering therapies for type-2 diabetic patients, which may cause cognitive/neurological impairment. Although the effects of hypoglycaemia in the brain have been extensively studied in neurons, how hypoglycaemia impacts the viability of adult neural stem cells (NSCs) has been poorly investigated. In addition, the cellular and molecular mechanisms of how hypoglycaemia regulates NSCs survival have not been characterized. Recent work others and us have shown that the pituitary adenylate cyclase-activating polypeptide (PACAP) and the glucagon-like peptide-1 receptor (GLP-1R) agonist Exendin-4 stimulate NSCs survival against glucolipoapoptosis. The aim of this study was to establish an in vitro system where to study the effects of hypoglycaemia on NSC survival. Furthermore, we determine the potential role of PACAP and Exendin-4 in counteracting the effect of hypoglycaemia. A hypoglycaemic in vitro milieu was mimicked by exposing subventricular zone-derived NSC to low levels of glucose. Moreover, we studied the potential involvement of apoptosis and endoplasmic reticulum stress by quantifying protein levels of Bcl-2, cleaved caspase-3 and mRNA levels of CHOP. We show that PACAP via PAC-1 receptor and PKA activation counteracts impaired NSC viability induced by hypoglycaemia. The protective effect induced by PACAP correlated with endoplasmic reticulum stress, Exendin-4 was ineffective. The results show that hypoglycaemia decreases NSC viability and that this effect can be substantially counteracted by PACAP via PAC-1 receptor activation. The data supports a potential therapeutic role of PAC-1 receptor agonists for the treatment of neurological complications, based on neurogenesis impairment by hypoglycaemia.

Mouse positioning device for blood brain barrier FUS exposure

Gaucher’s disease is an inherited metabolic disorder that results in a deficiency of the enzyme glucocerebrosidase, which acts on the glycolipid glucocerebroside. This causes a rapid accumulation of glucocerebroside in affected persons, which manifests in organ malfunctions and disfiguration, swelling, and severe neurologic complications, among other symptoms. Enzyme replacement therapy can manage the symptoms but when the brain is affected, the treatment is not effective since the enzymes cannot cross the blood brain barrier (BBB). Imaging of enzyme replacement therapy has shown that only insignificant amounts reach the brain.[1] In this work, we intend to evaluate brain uptake of enzyme replacement after BBB opening mediated by focused ultrasound (FUS) to validate this delivery technique for the treatment of neurologic complications caused by Gaucher’s disease. Our goal is to develop a system for Blood Brain Barrier delivery that can be followed up using positron emission tomography (PET) imaging. It will then be used to create and validate the delivery after intravenous injection of radiolabelled enzymes.

Prediabetes and type 2 diabetes implication in central proliferation and neurogenesis

Type 2 diabetes (T2D) is an important risk factor for developing dementias, including Alzheimer's disease (AD). Hyperinsulinemia and glucose intolerance, as features of T2D, might increase the neurodegeneration process, synaptic loss and brain atrophy, leading to cognitive impairment observed in AD. Also, adult neurogenesis seems to be impaired in AD models. Therefore, we have studied morphological alterations, cell proliferation and neurogenesis in the central nervous system (CNS) from a classical model of T2D, the db/db mouse, and in a prediabetes insulin-resistant model, obtained after long-term high fat diet (HFD) administration to C57Bl/6 mice. Db/db mice showed an age-dependent cortical and hippocampal atrophy, whereas in HFD mice cortex and hippocampus were preserved. Neurogenesis and cell proliferation were increased in young db/db mice, when compared with control mice, whereas no differences were detected in the prediabetic model. We also detected significant correlations between metabolic parameters and central atrophy, altered proliferation and neurogenesis in the central nervous system. Altogether these data support that glycaemia control in elderly patients, could help to control central alterations and improve dementia prognosis.

Можливості нейрометаболічної терапії в лікуванні неврологічних ускладнень цукрового діабету

В огляді описується вплив нейрометаболічної терапії з використанням Актовегіну на засвоєння глюкози, а також антиоксидантний, антигіпоксантний та інші механізми дії препарату. Розглядаються можливості нейрометаболічної терапії в лікуванні неврологічних ускладнень цукрового діабету. На підставі аналізу результатів великого числа досліджень зроблено висновок про те, що Актовегін може широко застосовуватися при діабетичній полінейропатії і діабетичній енцефалопатії.

Pituitary adenylate cyclase‐activating polypeptide counteracts the impaired adult neural stem cell viability induced by palmitate

Diabetes and obesity are characterized by hyperlipidemia and represent risk factors for premature neurological disorders. Diabetic/obese animals have impaired adult neurogenesis. We hypothesize that lipotoxicity leading to neurogenesis impairment plays a role in the development of neurological complications. If so, normalizing neurogenesis in diabetes/obesity could be therapeutically useful in counteracting neurological dysfunction. The goal of this study was to determine the potential of pituitary adenylate cyclase-activating polypeptide (PACAP) to protect adult neural stem cells (NSCs) from lipotoxicity and to study the expression of PACAP receptors in NSCs under lipotoxic conditions in vitro and in the subventricular zone in vivo. The viability of NSCs isolated from the adult mouse brain subventricular zone was assessed in the presence of a high-fat milieu, as mimicked by palmitate, which characterizes diabetic lipotoxicity. Regulation studies of PACAP receptors were performed by quantitative PCR on NSCs in vitro or on subventricular tissues isolated from obese ob/ob mice and their lean littermates. We show that palmitate impairs NSC viability by promoting lipoapoptosis. We also show that PACAP counteracts lipotoxicity via PAC-1 receptor activation. Studies on PACAP receptor expression revealed that PAC-1 and VPAC-2 are expressed by NSC in vitro and are upregulated by palmitate treatment and that PAC-1, VPAC-1, and VPAC-2 are expressed in the subventricular zone/striatum in vivo and are upregulated in ob/ob mice. The present study reveals a previously uncharacterized role of PACAP to protect NSC from lipotoxicity and suggests a potential therapeutic role for PACAP receptor agonists in the treatment of neurological complications in obesity and diabetes.

Comparable myelinated nerve pathology in feline and human diabetes mellitus

The occurrence of diabetic neuropathy in cats provides an opportunity to study the development and treatment of neurological complications not present in diabetic rodent models, where few pathological alterations are evident. The present study further defines pathological alterations in nerve biopsies from 12 cats with spontaneously occurring diabetes mellitus. Peroneal nerve biopsies displayed concurrent injury to both Schwann cells and axons of myelinated fibers that was remarkably similar to that present in human diabetic neuropathy. In addition to demyelination, remyelination (constituting 20-84% of the total myelinated fiber population) was indicated by fibers with inappropriately thin myelin sheaths. Unlike our previous investigations, striking axonal injury was apparent, and consisted of dystrophic accumulations of membranous debris or neurofilaments, as well as degenerative fiber loss resulting in a 50% decrease in myelinated fiber density. In spite of extensive fiber loss, regenerative clusters were apparent, suggesting that axonal regeneration was not completely frustrated. These data highlight the potential utility of feline diabetic neuropathy as a model that faithfully replicates the nerve injury in human diabetes mellitus.

Smallpox and smallpox vaccination: neurological implications.

Compulsory vaccination was discontinued in the U.S. in 1972; the world was declared free of smallpox infection in 1980. Since that time, no new smallpox infections have been recognized, and only limited numbers of military and laboratory personnel have been vaccinated. As a result, the majority of the U.S. and the world population have no or diminished immunity to smallpox. Widespread vaccination, beginning with the military and health care workers, is now being undertaken. Public health strategies for immunizing the general population include preexposure voluntary vaccination, case surveillance with ring vaccination, and mass vaccination at the time of attack. Cutaneous complications of vaccination occur in immunosuppressed subjects and in those with atopic dermatitis. Among the most serious complications is postvaccinal encephalomyelitis (PVEM). A related condition, postvaccinial encephalopathy (PVE), may be seen in children less than two years of age. There are no markers to predict who will develop PVEM. In the past, mortality was high, ranging from 10 to 50%. The neuropathology of PVEM suggested an immune-mediated attack on the CNS, but the target of the immune response is unknown. Comprehensive programs are needed for surveillance and confirming case definitions for neurologic complications. Multi-institutional controlled trials of antiviral and immune modulating therapy of PVEM should be considered. Neurologists should be actively involved in the planning process for vaccination programs and in the treatment of neurologic complications.