Central Nervous System Derangement Research Articles

FRI627 Lost In The Striato-sphere: Diabetic Striatopathy In An Elderly Patient Who Was Lost To Follow-up

Abstract Disclosure: C.L. Loughner: None. E. Mahmood: None. A. Sheharyar: None. Introduction: Diabetic striatopathy (DS) represents a spectrum of central nervous system derangements associated with uncontrolled hyperglycemia.1 The most common site of brain involvement is the putamen but can involve any region of the striatal nuclei. The exact mechanism behind DS remains unclear, but current theories postulate hyperosmolarity-related ischemic events that lead to breakdown in the blood-brain barrier and mineral deposition2. We present a case of DS demonstrating a rare neurologic complication resulting from uncontrolled diabetes mellitus. Clinical Case: An 82-year-old female was admitted for workup following new-onset left-sided involuntary jerking movements. On exam, there were choreiform movements in the left upper and lower extremities. Initially, Levetiracetam was started for possible focal motor seizures but with no improvement. MRI brain showed T1 hyperintensity of the right lentiform nucleus, consistent with DS. She had moved recently from out of state and had inconsistent follow-up for type 2 diabetes mellitus for years. Her HbA1c was 13.8%. She was non-compliant with glucose monitoring and insulin therapy. With a comprehensive treatment plan including Haloperidol, physical therapy, improved CGM compliance, and four-times-daily insulin regimen, her chorea improved and resolved completely over a few weeks. Clinical Lesson: DS can present with a variety of neurologic manifestations, including chorea. While choreiform movements can severely impact a patient’s life, they are rarely permanent if treated with either glycemic control or anti-chorea medications. This case highlights the importance to recognize rarer complications of diabetes and the impact of good glycemic control for successful treatment of diabetic striatopathy.

Patients with heat-related illness admitted to an intensive care unit in Hong Kong: A single-centre retrospective study (2009–2020)

Introduction: In Hong Kong, heat-related illness (HRI) represents an important cause of morbidity and mortality among healthy adults engaging in outdoor activities during summer. It can result in intensive care unit (ICU) admission. This retrospective study aimed to profile critically ill patients with HRI and identify potential risk factors for mortality. Methods: This retrospective case series included adults with HRI from 1 January 2009 to 30 June 2020 admitted to the ICU of Pamela Youde Nethersole Eastern Hospital (PYNEH). Demographics, admission severity, co-morbidities, and laboratory investigations were analysed. Outcome data studied included mortality, ICU length of stay (LOS), ventilator days, and hospital LOS. Results: Among the 38 individuals included, 97% were hikers. About 92.1% of patients survived, while 7.9% expired. The median age of the patients was 48 years, and 78.9% were men. Hypertension was the most frequent concurrent disorder. Most cases were presented during the hot summer months of May (29%), July (24%) and August (18%). The localities’ median peak temperature and humidity were 33.2°C and 88%, respectively. Ninety-two percent of patients were airlifted to the hospital by helicopters. The median peak body temperature was 40.3°C. Central nervous system derangement (Glasgow Coma Scale (GCS) score ⩽ 8) was the top presenting feature (65.7%). About 57.9% of patients required vasopressor support, followed by mechanical ventilation (50%) and renal replacement therapy (31.6%). Conclusions: Most critically ill patients suffering from HRI were hikers and middle-aged adults. Mortality was 7.9% despite advanced life support in ICU. Raising public awareness of the associated risk with hiking in hot summer is essential for the prevention of HRI.

Clinical outcome of severe sepsis and septic shock in critically ill children.

Information concerning the clinical outcome of severe sepsis and septic shock among the burden of tropical infections in children is limited, particularly in low-income settings. We conducted a prospective consecutive cohort study in all children aged 1 month to 16 years needing paediatric intensive care between 1 January 2017 and 31 December 2018. Demographic details, presenting symptoms and duration, associated co-morbidity and organ dysfunction were recorded. Clinical and laboratory parameters discriminating between survivors and non-survivors were evaluated. Most presented with respiratory or central nervous system derangement along with cardiovascular dysfunction. Haematological involvement was almost invariably found on diagnostic evaluation. Those children with ≥3 systems involved had higher odds of mortality. Dengue was seen in half the patients, being the commonest tropical infection. Not surprisingly, non-survivors were younger, had rapid progression of illness and needed ventilation more often within the first hour of admission. However, in multivariable regression analysis, only procalcitonin levels were associated with increased risk of mortality. We conclude that that tropical infections causing severe sepsis and septic shock are an important cause of mortality. There are, however, no clinical parameters which differentiate reliably between survivors and non-survivors.

Endometriosis-related chronic pelvic pain: A mini review on pathophysiology and impact on mental health

Endometriosis-related chronic pelvic pain is a major component of the disease that affects quality of life in women of reproductive age suffering from endometriosis. The present review summarizes current evidence upon pathophysiology and its impact on mental health. It seems that endometriosis-related chronic pelvic pain is the result of chronic stress on the central nervous system as a consequence of chronic pelvic inflammation. Mental health issues may rise as a result of central nervous system derangement and further aggravate pain perception and therefore quality of life. Further properly designed studies are needed in order to elucidate the connection between mental disorders and endometriosis-related chronic pelvic pain.

Clinical Characteristics and Outcome of Thyroid Storm: A Case Series and Review of Neuropsychiatric Derangements in Thyrotoxicosis

The objectives of this study were (1) to describe the presentation, demographics, and clinical course of patients admitted for thyroid storm, and (2) to identify factors associated with mortality. A retrospective review of subjects admitted to a single academic hospital from 2006 through 2011 was conducted. Medical records for all patients who were admitted with a diagnosis of thyrotoxicosis were systematically reviewed for clinical features of thyroid storm. A total of 28 cases were identified. Thyroid storm was the first clinical presentation of thyrotoxicosis in 13 patients (46.4%). Noncompliance with treatment was a major trigger in previously diagnosed patients, followed by infection. The mortality rate was 25% in this series. Cardiac manifestations were predominant, with >60% of patients having severe tachycardia (heart rate >140 beats per minunte) and/or atrial fibrillation. Although central nervous system (CNS) involvement was less frequent (n = 8, 28.6%), CNS derangement of worse than mild severity was statistically associated with mortality (P = .021). There was good agreement between the Burch-Wartofsky Point Scale and Japanese Thyroid Association criteria in the diagnosis of thyroid storm in this study cohort. Thyroid storm was the first presentation of thyrotoxicosis in a significant proportion of patients, highlighting the importance of a high index of suspicion in an appropriate clinical context. The presence of neuropsychiatric manifestations appeared to portend greater risk of mortality. Prevailing evidence suggests that there are complex interactions between thyroid hormones and neurotransmitter circuits in the pathogenesis of CNS symptomology in thyrotoxicosis.

Delivery of Sesamol-Loaded Solid Lipid Nanoparticles to the Brain for Menopause-Related Emotional and Cognitive Central Nervous System Derangements

The physicochemical nature of sesamol (logP 1.29; solubility 38.8 mg/mL) substantially enhances its tissue distribution, minimizing its brain delivery. Sesamol-loaded solid lipid nanoparticles (S-SLNs) with an average particle size of 122 nm and an entrapment efficiency of 75.9 ± 2.91% were developed. Biochemical and behavioral paradigms clearly established the superiority of orally administered S-SLNs. The same was confirmed evidently by scintigraphic images of rabbits administered radiolabeled SLNs and confocal microscopy of brain sections of rats administered similarly prepared SLNs with a fluorescent marker. This study indicates the special importance of using phosphatidylcholine (as co-surfactant) in the preparation of SLNs for improving memory deficits. The aim of the present work was to develop sesamol as a therapeutic agent for central nervous system derangements.

Parasympathetic dysfunction is associated with baroreflex and chemoreflex impairment in streptozotocin-induced diabetes in rats

This study explored physiological mechanisms of diabetic dysfunction in baroreceptors and chemoreceptors-mediated hemodynamic responses, and cholinergic neurotransmission in 30-day diabetic rats ( n = 14) and controls ( n = 14). Basal hemodynamic data and vagal response to electrical stimulation and methacholine injection were also evaluated. Muscarinic receptors were characterized using a radioligand receptor binding assay ([ 3H]N methylscopolamine). Experimental diabetes (50 mg/kg of STZ, i.v.) decreased systolic, diastolic, and mean arterial pressure and basal heart rate. Heart rate (HR) responses to vagal electrical stimulation (16, 32, and 64 Hz) were 15%, 11%, and 14% higher in diabetics vs non-diabetics, as were HR responses to methacholine injection (− 130 ± 24, − 172 ± 18, − 206 ± 15 bpm vs. − 48 ± 15, − 116 ± 12, − 151 ± 18 bpm, P < 0.05). Muscarinic receptor density was higher (267.4 ± 11 vs 193.5 ± 22 fmol/mg/prot, P < 0.05) in the atria of diabetic rats than in those of controls; the affinity was similar between groups. Diabetes-induced reduction of reflex responses to baro- (reflex bradycardia: − 3.4 ± 0.3 and − 2.7 ± 0.2 bpm/mm Hg; reflex tachycardia: − 1.6 ± 0.1 and − 1.4 ± 0.07 bpm/mm Hg, in control and diabetics, P < 0.05) and chemoreceptor stimulation, enhancement of HR responsiveness to cardiac vagal electrical stimulation and methacholine stimulation, plus an increase in the number of atrial muscarinic receptors indicates reduced parasympathetic activity, which is probably derived from central nervous system derangement.

Myelomeningocele: Characterization of a surgically induced sheep model and its central nervous system similarities and differences to the human disease

The purpose of this study was to determine how closely the surgically induced sheep myelomeningocele (MMC) model resembles the central nervous system derangements seen in human disease, and identify which aspects of MMC are the result of the early neuronal developmental defect, and which are secondary to the cerebrospinal fluid (CSF) drainage. An MMC-like lesion was created surgically in 16 fetal sheep at 75 days' gestation: 5 died in utero, 7 underwent no fetal repair, 4 were repaired (2-layer closure or biological glue) at 100 days' gestation. MMC sheep were delivered at term and allowed to survive up to 17 days for analysis of behavioral status and feeding behavior. Animals not repaired in utero were repaired at birth. All lambs were sacrificed and analyzed for hindbrain herniation, hydrocephalus, and other CNS derangements. Hindbrain herniation was observed in 43% of animals not repaired in utero, and in 1 lamb repaired with Bioglue. No animal developed hydrocephalus or other CNS derangements. Although this sheep MMC-like model reproduces the CSF leak, but not the developmental defect seen in humans, it suggests CSF leak contributes to hindbrain herniation seen in humans. This model may be useful to develop new minimally invasive techniques to halt CSF leak in utero.

Menopause and the central nervous system: intervention options

The central nervous system is an important target for sex steroid hormones. During the climateric period the rapid decline of gonadal steroids causes neuroendocrine changes in different areas of the brain. The failure of gonadal hormone production brings specific symptoms due to the central nervous system derangement. At the hypotalamic level estrogen withdrawal gives rise to vasomotor symptoms, eating behavior disorders and altered blood pressure control. Psychological disturbances such as depression, anxiety, irritability and mood fluctuation are related to estrogen-induced changes in the lymbic system. The hypothesis of specific neuroanatomical and neurophysiological effects of estrogen on the brain may also explain the correlation between estrogen deficiency and cognitive disturbances such as Alzheimer's type dementia (AD). The increasing interest in the influence of sex steroids on brain function has focused attention on hormonal replacement therapy. Clinical and epidemiological studies have demonstrated that estrogen therapy exerts a positive effect on vasomotor instability and improves psychological disturbances. The positive effects of estrogen on mood are probably related to its stimulatory action on adrenergic and serotoninergic tone. Estrogen may influence the cognitive function through different biological actions. Estrogen administration increases total cerebral and cerebellar blood flow, cerebral glucose administration and improves cholinergic tone, a key neurotransmitter in learning and memory. The evidence suggests that hormone replacement therapy may reduce the relative risk of developing AD. Progestagens and androgen may also have a role in the control of mood disorders. At present, few data are available regarding the influence that selective estrogen receptor modulators, a new class of compounds, can exert on the brain.

Ethylene Glycol Intoxication

Commonly available as automotive antifreeze, ethylene glycol can cause toxicity and death if ingested. It is metabolized to several aldehyde and acid intermediates that can cause severe metabolic acidosis, central nervous system derangements, cardiorespiratory failure, and acute renal failure. A presumptive diagnosis can often be made by assessment of the anion gap and the osmol gap and the finding of metabolic acidosis. Corroborating findings include oxalate crystalluria and urine that fluoresces on exposure to ultraviolet light. Recognition is important because there are specific treatment methods available. Therapy consists of administering sodium bicarbonate to counter the acidosis, ethanol to slow the generation of toxic metabolites, and vitamin cofactors, which may speed detoxification of these intermediates. Hemodialysis is employed to remove both ethylene glycol and its metabolites, to correct the acidbase disturbances, and as treatment for acute renal failure.

Serum Ammonia Levels in Response to Glycine Infusion in Normal and Cirrhotic Rats

Elevated serum ammonia may play a role in central nervous system derangement after transurethral resection of the prostate. Glycine used as a surgical irrigant for prostate resection produces ammonia as a by-product after liver and renal metabolism. The presence of liver dysfunction often leads to an inability to remove generated ammonia from the circulation. To determine whether the presence of cirrhosis allows significant metabolism of glycine and the resulting serum ammonia levels generated, the production of ammonia after glycine infusion was examined in normal and cirrhotic rats. Hepatic microsomal enzyme induction was produced in male Sprague-Dawley rats given sodium phenobarbital, added to the drinking water to hasten the development of cirrhosis, by increasing the toxicity of carbon tetrachloride given intragastrically to one group at weekly intervals for production of cirrhosis. A control group was maintained under similar conditions except for carbon tetrachloride dosing. The end point for production of cirrhosis was the development of ascites. Two weeks after the development of ascites in the cirrhotic rats and the discontinuation of phenobarbital in both groups, both control and cirrhotic rats were anesthetized with IP pentobarbital and glycine (1.25 g/kg; 7.5%) was given intravenously. Venous blood samples were taken at intervals up to 120 min for serum ammonia analysis. After the final serum ammonia sample, lethal pentobarbital injection was given and livers and kidneys removed for histologic analysis. Terminal body weight, glycine dose, and renal histology were not different between groups. Liver weights were greater in cirrhotic rats. Baseline serum ammonia levels were also greater int he cirrhotic rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypernatremia

Hypernatremia is a potentially life-threatening electrolyte abnormality. This problem develops most often because of loss of water from the animal, but in rare cases hypernatremia results from gain of sodium chloride. Important conditions predisposing to hypernatremia include diarrhea, vomiting, heat stroke, fever, limited access to water, excessive diuretic use, renal diseases, and pituitary diabetes insipidus. This condition rarely develops if animals have adequate access to water. Clinical signs relate to central nervous system derangements and can progress to seizures and coma. Diagnosis is based on the serum sodium concentration; treatment should be instituted if it is greater than 170 mEq per L. Treatment is based on knowledge of the volume status of the patient and the probable cause for the hypernatremia. In general, 5 per cent dextrose in water or other hypotonic fluids are given slowly intravenously. The rate of administration should be adjusted so the water deficit is replaced over 48 to 72 h. Too rapid correction of hypernatremia can lead to cerebral edema and worsening of the animal. In cases of salt intoxication, diuretics must be given in addition to slow water replacement to avoid the development of pulmonary edema.

Polioencephalomalacia (PEM)-Current research status

In ruminants fed high grain rations, a condition called polioencephalomalacia (PEM), characterized by central nervous system derangement, can develop. It usually is noninfectious, responds to thiamin injections, and is characterized by sudden onset. Using artificial rumen techniques, we established that PEM results from a bacteria-produced enzyme in the rumen that converts the vitamin thiamin to a nonusable alternate form, pyrithiamin, which in turn caused severe metabolic disturbances in the central nervous system.

Respiration and the cerebrospinal fluid in experimental cerebral concussion.

I N recent years there has been increasing interest in the respiratory complications of cerebral trauma as well as the role of the cerebrospinal fluid (CSF) in respiration. 9 Published reports have concentrated on the respiratory, acid-base, and blood gas alterations seen in more severe forms of cranial trauma where the comparability of the level of injury was questionable, and multiple injuries were frequently involved. The question then arises: What part of the devastating effects of respiratory disturbance after cranial trauma is precipitated by primary neurogenic factors and what part follows as secondary effects of airway obstruction and pulmonary insufficiency? Ducker and associates have helped to elucidate part of this problem in their study of the role of raised intracranial pressure and the Cushing reflex in the genesis of pulmonary edema after head injury. ~,~,21 In an attempt to separate the primary central nervous system derangements from those caused by secondary airway and pulmonary factors, we have begun a study of respiratory function, blood, and CSF pH and gas tensions after experimental cerebral concussion (ECC). This model of head injury represents our baseline of minimal and reversible brain trauma wherein the physiopathology of blunt head injuries may be analyzed, and on which studies of more severe injury may be built. The criteria for concussion and the biomechanical aspects of the trauma were developed for the Rhesus monkey, as previously described by Ommaya, et al. ~,6,17,~8

Congenital Familial Nonhemolytic Hyperbilirubinemia in an Adult with Central Nervous System Derangement

Summary The clinical and laboratory findings in a 22-year-old Pakistani male with congenital familial nonhemolytic indirect hyperbilirubinemia are described. Jaundice began at an early age, and abnormal deposition of unconjugated bilirubin presumably caused severe central nervous system derangement. The liver was normal histologically and no evidence of hepatic, extrahepatic, or hemolytic disturbances was demonstrated. A 10-year-old sister of the patient showed moderate elevation of indirect reacting bilirubin without evidence of central nervous system involvement. The probable functional abnormality of the patient and his sister is a deficiency of the glucuronyl transferase enzyme system.

Cerebral palsy: A practical routine for discerning oculomotor defects in cerebralpalsied children

Summary Ocular defects exist in over 50 percent of patients with cerebral palsy resulting from central nervous system derangement. These ocular motor defects shouldbe detected before degeneration of vision occurs in these children. Early treatment of these motor defects will develop vision and may improve general motor ability, especially in patients with athetosis or ataxia. Simple tests are, therefore, suggested for detecting the presence of strabismus by the corneal reflection test, conjugate defects by the motility test, and subnormal vision by the means of the “E” game. An “E” chart for 10 feet distance testing instead of 20 feet distance is presented. This “E” chart gives percentages of visual efficiency as well as ordinary visual notations. Other tests such as the near visionand fixation tests are purposely omitted in this paper.