Jasvinder Chawla, MD, MBA Chief Neurology, Hines Veterans Affairs Hospital, Professor of Neurology, Loyola University Medical Medical Center Jasvinder Chawla, MD, MBA is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, American Clinical Neurophysiology Society, American Medical Association. Specialty Editor Board Francisco Talavera, PharmD, PhD Adjuct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Editor-in-Chief, Medscape Drug Reference Howard S Kirshner, MD Professor of Neurology, Psychiatry and Hearing and Speech Sciences, Vice Chairman, Department of Neurology, Vanderbilt University School of Medicine, Director, Vanderbilt Stroke Center, Program Director, Stroke Service, Vanderbilt Stallworth Rehabilitation Hospital, Consulting Staff, Department of Neurology, Nashville Veterans Affairs Medical Center. Chief Editor Helmi L Letsep, MD Professor and Vice Chair, Department of Neurology, Oregon Health and Science University School of Medicine, Associate Director, OHSU Stoke Center Additional Contributors Pitchaiah Mandava, MD, PhD Assistant Professor, Department of Neurology, Baylor College of Medicine, Consulting Staff, Department of Neurology, Michael E DeBakey Veterans Affairs Medical Center. Richard M Zweifler, MD Chief of Neurosciences, Sentara Healthcare, Professor and Chair of Neurology, Eastern Virginia Medical School. 1 Thomas A Kent, MD Professor and Director of Stroke Research and Education, Department of Neurology, Baylor College of Medicine, Chief of Neurology, Michael E DeBakey Veterans Affairs Medical Center. Course Content Definitions Practice Essentials Signs and symptoms of Hyperglycemia Hyperglycemia in Stroke Diabetes Mellitus Proposed mechanisms for Hyperglycemia and worsened outcomes Possible protective effects of Hyperglycemia in lacunar stroke subtype Hypoglycemia in stroke like occurrences Signs and symptoms of Hypoglycemia Evaluation of Glycemic level and stroke Hypoglycemic symptoms and manifestations Central nervous system Laboratory studies Imaging studies Management Hyperglycemia Hypoglycemia Diagnosis Routine tests CT scanning of head Therapy in Hyperglycemia Consultations Acute Hyperglycemic therapy Intensive insulin therapy Sulfonylurea agents Complications Therapy in Hypoglycemia 2 Definitions Hyperglycemia (also spelled hyperglycaemia or hyperglycæmia), is a condition in which an excessive amount of glucose circulates in the blood plasma. This is generally a blood sugar level higher than 11.1 mmol/l (200 mg/dl), but symptoms may not start to become noticeable until even higher values such as 13.9–16.7 mmol/l (~250–300 mg/dl). A subject with a consistent range between ~5.6 and ~7 mmol/l (100–126 mg/dl) (American Diabetes Association guidelines) is considered slightly hyperglycemic, and above 7 mmol/l (126 mg/dl) is generally held to have diabetes. For diabetics, glucose levels that are too hyperglycemic can vary from person to person, mainly due to the person's renal threshold of glucose and overall glucose tolerance. On average, however, chronic levels above 10–12 mmol/L (180–216 mg/dl) can produce noticeable organ damage over time. White hexagons in the image represent glucose molecules, which are increased in the lower image. Hypoglycemia, also known as low blood sugar, is a fall in blood sugar to levels below normal. This may result in a variety of symptoms including clumsiness, trouble talking, confusion, loss of consciousness, seizures or death. A feeling of hunger, sweating, shakiness and weakness may also be present. Symptoms typically come on quickly. The most common cause of hypoglycemia is medications used to treat diabetes mellitus such as insulin and sulfonylureas. Risk is greater in diabetics who have eaten less than usual, exercised more than usual or drunk alcohol. Other causes of hypoglycemia include kidney failure, certain tumours (such as insulinoma), liver disease, hypothyroidism, starvation, inborn error of metabolism, severe infections, reactive hypoglycemia and a number of drugs including alcohol. Low blood sugar may occur in otherwise healthy babies who have not eaten for a few hours. 3 The glucose level that defines hypoglycemia is variable. In people with diabetes, levels below 3.9 mmol/L (70 mg/dL) are diagnostic. In adults without diabetes, symptoms related to low blood sugar, low blood sugar at the time of symptoms and improvement when blood sugar is restored to normal confirm the diagnosis. Otherwise, a level below 2.8 mmol/L (50 mg/dL) after not eating or following exercise may be used. In new-borns, a level below 2.2 mmol/L (40 mg/dL), or less than 3.3 mmol/L (60 mg/dL) if symptoms are present, indicates hypoglycemia. Other tests that may be useful in determining the cause include insulin and C peptide levels in the blood. Practice Essentials Pre-existing hyperglycemia worsens the clinical outcome of acute stroke. Nondiabetic ischemic stroke patients with hyperglycemia have a 3-fold higher 30-day mortality rate than do patients without hyperglycemia. In diabetic patients with ischemic stroke, the 30-day mortality rate is 2-fold higher. With regard to hypoglycemia, the condition can mimic acute stroke or symptoms of transient ischemic attack (TIA). Signs and symptoms in Hyperglycemia The degree of hyperglycemia can change over time depending on the metabolic cause, for example, impaired glucose tolerance or fasting glucose, and it can depend on treatment. Temporary hyperglycemia is often benign and asymptomatic. Blood glucose levels can rise well above normal and cause pathological and functional changes for significant periods without producing any permanent effects or symptoms. During this asymptomatic period, an abnormality in carbohydrate metabolism can occur which can be tested by measuring plasma glucose. Chronic hyperglycemia at above normal levels can produce a very wide variety of serious complications over a period of years, including kidney damage, neurological damage, cardiovascular damage, damage to the retina or damage to feet and legs. Diabetic neuropathy may be a result of long-term hyperglycemia. Impairment of growth and susceptibility to certain infection can occur as a result of chronic hyperglycemia. Acute hyperglycemia involving glucose levels that are extremely high is a medical emergency and can rapidly produce serious complications (such as fluid loss through osmotic diuresis). It is most often seen in persons who have uncontrolled insulin-dependent diabetes. The following symptoms may be associated with acute or chronic hyperglycemia, with the first three composing the classic hyperglycemic triad: • Polyphagia – frequent hunger, especially pronounced hunger • Polydipsia – frequent thirst, especially excessive thirst • Polyuria – increased volume of urination (not an increased frequency, although it is a common consequence) • Blurred vision • Fatigue • Restlessness • Weight loss • Poor wound healing (cuts, scrapes, etc.) • Dry mouth • Dry or itchy skin • Tingling in feet or heels • Erectile dysfunction • Recurrent infections, external ear infections (swimmer's ear) • Cardiac arrhythmia 4 • Stupor • Coma • Seizures Frequent hunger without other symptoms can also indicate that blood sugar levels are too low. This may occur when people who have diabetes take too much oral hypoglycemic medication or insulin for the amount of food they eat. The resulting drop in blood sugar level to below the normal range prompts a hunger response. Polydipsia and polyuria occur when blood glucose levels rise high enough to result in excretion of excess glucose via the kidneys, which leads to the presence of glucose in the urine. This produces an osmotic diuresis. Signs and symptoms of diabetic ketoacidosis may include: • Ketoacidosis • Kussmaul hyperventilation (deep, rapid breathing) • Confusion or a decreased level of consciousness • Dehydration due to glycosuria and osmotic diuresis • Increased thirst • 'Fruity' smelling breath odour • Nausea and vomiting • Impairment of cognitive function, along with increased sadness and anxiety • Weight loss Hyperglycemia causes a decrease in cognitive performance, specifically in processing speed, executive function, and performance. Decreased cognitive performance may cause forgetfulness and concentration loss. Hyperglycemia in stroke Pre-existing hyperglycemia is found commonly in patients presenting with acute stroke and is reported to be present in 20 to 50% of patients. In many trials of thrombolytic agents, hyperglycemia occurred in about 20-30% of subjects. Although confounded by other factors, such as severity of the infarct, hyperglycemia in the face of acute stroke worsens clinical outcome. Nondiabetic hyperglycemic ischemic stroke patients have a 3- fold higher 30-day mortality and diabetic patients have a 2-fold 30-day mortality. In several trials involving thrombolytic and anticoagulation therapy in patients with stroke, hyperglycemia appears to be an independent risk factor for worsened outcome. In addition, hyperglycemia has been suggested as an independent risk factor in hemorrhagic conversion of the stroke after administration of thrombolytic therapy. Several case reports describe hypoglycemia mimicking acute stroke or symptoms of transient ischemic attack (TIA). Berkovic et al reported that hypoglycemia was the cause of symptoms mimicking acute stroke in 3 of 1460 patients admitted to their stroke unit over a 5-year period. Diabetes mellitus Diabetes mellitus is an independent