hypoglycemic brain injury



OVERVIEW

Definition of Hypoglycemic Brain Injury

Hypoglycemic brain injury, also known as hypoglycemic encephalopathy, refers to a series of neurological and psychiatric symptoms triggered by severe hypoglycemia due to various reasons.

Patients usually first experience sympathoexcitatory syndromes such as extreme hunger, sweating, anxiety, restlessness, irritability, palpitations, trembling of hands and feet, pallor, and agitation, followed by impaired consciousness, abnormal demeanor, convulsions, and even coma [1-2].

At this time, blood glucose may be less than 2.8 mmol/L in adults and less than 2.2 mmol/L in infants and children.

Morbidity

There are no exact incidence figures for hypoglycemic brain injury in China.

The incidence of severe hypoglycemia in patients with type 1 diabetes mellitus is 20% to 40%. In patients with type 1 diabetes mellitus with a disease duration of more than 15 years, the incidence of severe hypoglycemia is 3.2 times/(person-year) [5].

Some studies have shown that the incidence of severe hypoglycemia in patients with type 2 diabetes mellitus treated with insulin is 10% to 30%. Of these, 50% of severe hypoglycemia occurs during nocturnal sleep [5].

Etiology

Pathogenesis

The central aspect of the pathogenesis of hypoglycemic brain injury is the source of blood glucose less than the way to go, including the body’s glucose intake is reduced, hepatic glycogenolysis and gluconeogenesis is reduced and the body’s tissues consume and utilize glucose increased two aspects.

Reduced source of blood glucose

Severe malnutrition; liver failure due to severe hepatitis, cirrhosis, and advanced hepatocellular carcinoma.

Renal failure due to renal insufficiency from various causes.

Lack of hormones in the body that raise blood glucose, such as glucagon deficiency, hypoadrenocorticism with decreased glucocorticoid secretion and epinephrine deficiency.

Increased blood glucose de-escalation

Autonomous secretion of excess insulin due to insulinoma and pancreatic beta cell hyperplasia.

Inborn disorders of glucose metabolism such as gluconeogenesis.

Autonomic dysfunction such as idiopathic functional hypoglycemia.

Inappropriate oral hypoglycemic drugs and insulin injections.

Severe diarrhea, high fever and severe hyperthyroidism.

Excessive glucose consumption after strenuous exercise or prolonged heavy physical labor.

Risk factors

Hypoglycemic encephalopathy can occur at any age and in any group of people, with the elderly, pregnant women, infants, and children being susceptible.

In diabetic patients, it is especially seen in the following conditions: prolonged duration of the disease, taking sulfonylurea hypoglycemic drugs, antihypertensive drugs, and hepatic and renal insufficiency.

Pathogenesis

When the body’s blood sugar drops, the body takes a number of steps to protect the brain.

First, the body releases glucagon and epinephrine to increase blood flow to the brain and prevent damage to the nervous system. At the same time, these substances stimulate the liver to produce more sugar, which returns blood sugar to normal. When these protective measures are not enough to return blood sugar to normal, hypoglycemia may cause damage to the brain.

Hypoglycemia can be very damaging to the brain because it causes brain cells to lack energy and cell membranes to become unstable, affecting synaptic transmission, which can lead to impaired brain function.

Hypoglycemia also causes the pH inside the brain to rise, creating an alkaline environment, which can cause neuron cells to become edematous and trigger dysfunction.

Hypoglycemia also stimulates the body’s sympathetic nervous system to release adrenaline and a number of peptides that can cause cerebral vasospasm. This causes brain cells to become ischemic and hypoxic, triggering edema, which may lead to altered consciousness, coma and even seizures.

If severe hypoglycemia is left uncorrected for a long period of time, it may lead to permanent neurological damage or even death.

Different brain tissues tolerate hypoglycemia differently. In general, more evolved brain tissue, such as the cerebral cortex, is more sensitive and less tolerant to sugar deficiency.

Symptoms

Main Symptoms

Hypoglycemic brain damage is mainly characterized by sympathetic hyperexcitability and central nervous system dysfunction. The manifestations are related to the rate and duration of blood glucose drop, individual response and primary disease. Symptoms may occur if blood glucose drops too rapidly, even if the blood glucose value is within the normal range.

Rapid decline in blood glucose

It is often seen in patients in the early stages of diabetes, especially those treated with oral hypoglycemic agents or insulin.

Sympathetic symptoms such as extreme hunger, restlessness, pallor, profuse sweating, tachycardia, dizziness, headache, tremor of limbs and increased blood pressure may occur.

Slow decline of blood glucose

The main manifestation of central inhibitory symptoms:

Cortical inhibitory symptoms include dizziness, mania, abnormal behavior, hazy consciousness or drowsiness, slow thinking and speech, tremor, disorientation, and loss of recognition.

Symptoms of subcortical inhibition include restlessness, pain hypersensitivity, involuntary muscle twitching or twisting (myoclonus, choreographic movements), sucking, clenching of hands, and making faces (obsessive-compulsive movements).

Dilated pupils, generalized rigidity, convulsions, coma, loss of reflexes, drop in blood pressure, weakened respiration, etc. may also occur. At this time, if not timely treatment of sugar supplementation, irreversible damage can be produced, and ultimately die due to respiratory and circulatory failure.

Other symptoms

Cardiovascular system symptoms

When hypoglycemic brain damage occurs, the sympathetic nerve is stimulated, prompting peripheral vasoconstriction, elevated blood pressure, tachycardia, arrhythmia.

Elderly patients with pre-existing coronary artery disease may develop angina pectoris (pain and discomfort in the anterior region of the heart), or even myocardial infarction, and patients with pre-existing heart failure may aggravate their heart failure.

Symptoms in newborns, infants and young children

Low birth weight babies, diabetic pregnant women’s newborns, infants and young children can be manifested as not good at drinking milk, easy to cry, pale, cold sweat, poor concentration, nightmares, easy to scare, enuresis and so on.

Other manifestations

Asymptomatic hypoglycemic attack: diabetic patients who have been ill for a long time and have low glucagon response during hypoglycemia can directly experience hypoglycemic coma without aura symptoms.

Post-alcoholic hypoglycemia: diabetic patients and patients with liver dysfunction are prone to post-alcoholic hypoglycemia after drinking a large amount of alcohol. The performance of unsteady gait, slow reaction and drowsiness can be easily mistaken for drunkenness.

Consultation

Department of Medicine

Emergency Department

If the onset of the disease is rapid, and the patient quickly becomes unconscious or even comatose, he/she can go to the emergency department, especially the emergency neurology department.

Endocrinology

People with symptoms such as extreme hunger, pale skin, sweating, sensory abnormalities, mental behavioral abnormalities, drowsiness, and blurred consciousness, especially diabetic patients, need to go to the Endocrinology Department.

Infants, children, and adolescents with onset of symptoms can go to the Department of Pediatrics.

Preparation

Consultation: Registration, Preparation of Information, Frequently Asked Questions

Tips for Consultation

Early and timely consultation is recommended to avoid delay in diagnosis and treatment.

If hypoglycemia is suspected, oral sugar-containing substances (e.g., sugar-sweetened beverages, sugar cubes, cookies, etc.) should be given immediately, and self-measurement of blood glucose can be done if possible.

Prepare relevant medical records before seeking medical treatment.

Checklist for preparing for medical treatment

Particular attention needs to be paid to the time of onset of symptoms, special manifestations, etc.

When did the symptoms start? Did the symptoms progress?

Did you have hunger pangs, palpitations, shaking hands, cold sweats, etc. before the onset of symptoms?

Have similar symptoms occurred before? How did they resolve?

Are there any other accompanying symptoms, such as impaired limb mobility, angina pectoris, speech impediment, etc.?

Is there a history of diabetes mellitus, insulinoma?

Are there any diseases such as cortisol hormone deficiency, liver or kidney failure, severe infections and malnutrition?

Any recent dieting or excessive exercise?

Have you visited any other hospitals? What medications are you currently taking? Has there been any adjustment of the treatment program?

Examination results in the past six months, which can be brought to the doctor’s office

Imaging tests: cranial CT, cranial MRI, chest CT, abdominal ultrasound, etc.

Laboratory tests: blood routine, blood biochemistry (liver and kidney function, blood lipids, blood sugar, blood electrolytes, cardiac enzymes, etc.), coagulation function.

Other tests: electrocardiogram, cardiac color ultrasound, electroencephalogram.

Medication in the last 3 months, if there is a box or package of medication, you can bring it with you to the doctor’s office

Insulin: Glucagon, Mentholatum insulin, Ditropan insulin, etc.

Glucose-lowering drugs: Metformin, Bayerisepine, Glimepiride, Sitagliptin, glucose-lowering health products, etc.

Other drugs: such as antihypertensive drugs, psychotropic drugs such as diazepam, paroxetine, olanzapine, etc.

Diagnosis

Diagnosis is based on

Medical history

The patient may have a history of diabetes mellitus and recent adjustments to glucose-lowering medications.

The patient may have dieting, fasting exercise, alcohol consumption, overexertion, and gastrointestinal dysfunction.

The patient may have systemic chronic diseases, such as islet cell tumor, pituitary tumor, hypoadrenalism, cirrhosis of the liver.

Symptoms

Hunger, cold sweat, pallor, palpitation, hand tremor, generalized weakness.

Fainting, drowsiness, coma, seizures.

Mental disorders such as mannerisms, strangeness, disorientation, recognition, memory loss, fear and mania.

Physical Examination

The doctor will first check the patient’s general condition and vital signs, such as temperature, breathing, blood pressure, and pulse.

Patients with hypoglycemic encephalopathy may have an increased heart rate and pulse, and decreased blood pressure.

Consciousness: Determine the state of consciousness by calling the patient or asking questions.

Tendon reflexes: the degree of activity of tendon reflexes is determined by tapping on the periosteum or tendons with a percussion hammer, which may be absent or hyperactive.

Pathological signs: use a blunt-tipped swab to gently stroke the sole of the foot to determine the presence or absence of pathological reflexes.

Motor system and muscle strength: determine motor function and muscle strength by lifting hands, legs, and walking.

Higher cortical functions: Judge the cortical functions such as language, calculation and memory through question and answer and calculation.

Involuntary movements: severe cases of encephalopathy may have tremor of hands and feet, choreography, sucking, making ghost face and other movements.

Laboratory Tests

Common items: including blood glucose, liver and kidney function, thyroid function, serum insulin, C-peptide, β-hydroxybutyric acid, and insulinogen markers.

Examination purpose: to clarify the blood glucose situation, to find out whether there is liver and kidney function damage or systemic system diseases, such as diabetic ketoacidosis, liver failure, insulinoma, etc..

Precautions: Fasting is required before blood sampling, but emergency blood collection is required for comatose patients in critical condition.

It can detect the presence of abnormal brain cell discharges and determine the presence of epilepsy.

The EEG of patients with this disease may show diffuse slow waves and epileptic discharges in those with epilepsy.

Precautions: Hair should be washed and no hairspray applied before the test, and sedatives and stimulants should be discontinued before the test.

CT or magnetic resonance examination (MRI)

Includes a CT or MRI of the head.

It can rule out other brain injury lesions, such as cerebral hemorrhage and brain stem infarction.

Note: Patients wearing metal dentures, having heart stents, pacemakers, and other metal objects in their bodies should consult with their doctor before the examination to determine if the examination can be performed.

Diagnostic Criteria

The disease is mainly diagnosed based on the following criteria

Presence of hypoglycemia: for non-diabetics, the diagnostic criterion is a blood glucose level <2.8 mmol/L; for diabetics, the diagnostic criterion is a blood glucose level ≤3.9 mmol/L [6].

There were central nervous system symptoms and localized brain symptoms caused by hypoglycemia.

Hypoglycemic symptoms resolved rapidly after sugar supply.

The EEG is diffuse with slow waves and in epileptics there are epileptiform waves such as spike-slow waves.

Common causes of hypoglycemia can be identified, such as insulin overdose or insulinoma, severe liver disease, glycogen accumulation, alcoholism, and adrenocortical or anterior pituitary disease.

Differential diagnosis

Differential diagnosis is needed from all diseases that can cause neurologic damage or impaired consciousness:

Acute hypoxic encephalopathy

Caused by acute massive blood loss, severe heart failure, cardiac arrest and hypoxemia.

Similarities: patients may have symptoms of sympathetic excitation such as restlessness, euphoria, agitation, unresponsiveness, and in severe cases, impaired consciousness.

Differences: Patients with hypoglycemic encephalopathy have a longer time to develop symptoms, usually 30-60 minutes, whereas patients with hypoxic encephalopathy develop them within a few seconds or minutes of the immediate onset, with cyanosis and bruising, and no decrease in blood glucose.

Transient ischemic attack

It is a cerebral dysfunction caused by a decrease in cerebral blood flow for a short period of time.

Similarities: both may present with transient neurologic deficits such as confusion, aphasia, and no infarct foci in the brain on cranial MRI/CT.

Differences: transient cerebral ischemia may present with localized neurological deficits such as hemiparesis, hemiplegia, hemiplegia, and no hypoglycemia at the time of the attack.

Diabetic ketoacidosis

Similarities: both have a history of diabetes mellitus, both have varying degrees of impaired consciousness.

Differences: diabetic ketoacidosis patients have rotten apple odor in exhaled breath, positive urine ketone body, blood gas analysis suggests metabolic acidosis, and blood glucose is higher than normal value.

Hepatic coma

Similarity: Both can present with coma symptoms.

Differences: patients with hepatic coma have elevated blood ammonia and abnormal liver function.

Treatment

Aim of treatment: correct hypoglycemia, reduce nerve damage, avoid coma, death and other serious consequences.

Treatment principle: replenish glucose as soon as possible, deal with the cause as well as the blood glucose level, and relieve the cause of hypoglycemic brain damage.

Dietary treatment

For mild cases, hypoglycemia can be corrected by simply eating foods containing carbohydrates such as cookies and bread, sugar cubes, and chocolate.

Cow’s milk and milk contain fat and protein, which prevents blood sugar from rising too quickly.

Medication

Glucose.

Fast and effective, the drug of choice.

Including glucose water solution, glucose injection.

Oral glucose water solution can be used for mild cases; for severe cases, especially those who are unconscious, 50% glucose can be pushed intravenously, followed by intravenous drip of 5% to 10% glucose solution.

Precautions: 50% dextrose injection can cause intravenous drip extravasation, phlebitis, resulting in local pain, redness and swelling.

Glucagon

It can antagonize insulin and raise blood glucose rapidly and effectively.

It is mainly used for patients who cannot infuse glucose injection in time.

Cautions: short maintenance time, need to eat or enteral nutrition as soon as possible after the use of drugs to avoid the occurrence of another hypoglycemia.

Glucocorticoid

Glucocorticoid can be used appropriately to reduce cerebral edema in patients whose consciousness still cannot turn clear after glucose and glucagon treatment.

Commonly used drugs: dexamethasone, methylprednisolone and so on.

Precautions: Pay attention to the side effects of hormones, such as inducing or aggravating peptic ulcer, aggravating infections, etc., and need to protect the gastric mucosa at the same time, such as giving omeprazole.

Other treatments

Brain cell protection therapy

It can reduce necrosis of brain cells, reduce cerebral edema and protect brain cells.

Commonly used drugs: mannitol, glycerol fructose, cytarabine, nicergoline and ginkgo biloba preparation.

Precautions: The use of dehydrating agents should pay attention to the monitoring of electrolytes and renal function.

Potassium supplementation therapy

Avoid or reduce hypokalemia caused by the transfer of potassium ions into the cells during glucose supplementation.

Commonly used drugs: potassium chloride tablets or potassium chloride injection.

Precautions: Close monitoring of blood potassium and avoiding too rapid potassium supplementation are needed during treatment.

Antiepileptic drugs

The purpose is to prevent and terminate epileptic seizures.

Commonly used drugs: sodium valproate and lamotrigine.

Precautions: Monitor the liver and kidney functions and avoid arbitrary dosage and sudden stoppage of drugs, which may lead to epileptic status quo.

Surgery

The aim is to remove the insulinoma to reduce the occurrence of fasting hypoglycemia.

Surgical modalities: including insulinoma removal, pancreatic segmental resection, pancreaticoduodenectomy, pancreatic body-tail resection, total pancreatectomy, and so on.

Indications: All symptomatic insulinomas should be operated as soon as possible after diagnosis.

Contraindications: malignant insulinoma that cannot be completely resected from metastatic lesions; those who cannot tolerate surgery, such as those suffering from severe heart and lung diseases.

Precautions: “rebound hyperglycemia” may occur after surgery, and the doctor will add insulin appropriately. Usually it will gradually improve in 2 weeks.

Prognosis

Cure

Most cases have a good prognosis when diagnosed and treated promptly.

Severe sudden drops in blood glucose that last for a long time can lead to permanent mental impairment and other symptoms of neurological damage.

Hazards

Hypoglycemic brain damage occurs at the same time will induce cardiovascular disease, such as angina pectoris, or even myocardial infarction, heart failure and so on.

Prolonged hypoglycemic brain damage leads to brain tissue damage, leaving behind cognitive impairment, dementia, limb paralysis, epilepsy and other neurological sequelae.

Failure to timely correct hypoglycemia in newborns can result in extensive brain damage, leading to mental retardation; cognitive impairment and behavioral abnormalities in adulthood.

Daily

Daily Management

Dietary management

Dietary management should be carried out under doctor’s guidance.

Eat regularly, do not diet excessively, do not drink alcohol, and avoid excessive fluctuation of blood glucose.

For those who use insulin therapy, meals must be taken half an hour after injection, and meals can be added flexibly [11-13].

When the amount of food is reduced and the amount of exercise is increased, the dosage of hypoglycemic drugs should be reduced.

Regular eating: avoid prolonged fasting, infants and young children need to be fed on demand, adults should eat regularly and add meals appropriately.

Life management

Diabetic patients need to take medication regularly, do not adjust the medication or stop the medication on your own.

Exercise in moderation, pay attention to monitor the blood glucose before bedtime, low blood glucose should be added to the appropriate amount of meals.

Psychological support

Family members should cooperate with doctors to guide patients to correctly understand the disease, receive more popular science education, and establish confidence in the treatment of the disease, so as to handle and treat hypoglycemia in a timely manner.

Do not listen to, blindly follow the traveling doctors, and do not take the traditional Chinese medicine.

When the patient is found to be emotionally unstable, anxious or depressed, family members should seek timely help from medical staff for drug intervention and psychological counseling.

Disease monitoring

Diabetic patients should be regularly checked outpatient review of blood glucose, blood and urine routine, liver and kidney function, insulin, C-peptide and so on. If there are symptoms of unstable blood sugar fluctuations timely follow-up.

Prevention

In order to prevent this disease, diabetic patients and other people at high risk of this disease need to pay attention to the following points in their daily lives [13-15].

For the treatment of diabetic patients, hypoglycemic drugs should be gradually increased from a small dose to find the optimal amount for each patient.

Carry sugar cubes and cookies with you, take them in time when hypoglycemic reaction occurs, and seek medical treatment as early as possible.

Avoid strenuous exercise and drinking alcohol on an empty stomach.

Do not adjust the dosage of hypoglycemic drugs on your own.