Neuroglycopenia
Encyclopedia
Neuroglycopenia is a medical term that refers to a shortage of glucose
(glycopenia) in the brain
, usually due to hypoglycemia
. Glycopenia affects the function of neurons, and alters brain function and behavior. Prolonged neuroglycopenia can result in permanent damage to the brain.
Not all of the above manifestations occur in every case of hypoglycemia. There is no consistent order to the appearance of the symptoms. Specific manifestations vary by age and by the severity of the hypoglycemia. In older children and adults, moderately severe hypoglycemia can resemble mania, mental illness, drug intoxication, or drunkenness. In the elderly, hypoglycemia can produce focal stroke-like effects or a hard-to-define malaise. The symptoms of a single person do tend to be similar from episode to episode.
In the large majority of cases, hypoglycemia severe enough to cause seizures or unconsciousness can be reversed without obvious harm to the brain. Cases of death or permanent neurologic damage occurring with a single episode have usually involved prolonged, untreated unconsciousness, interference with breathing, severe concurrent disease, or some other type of vulnerability. Nevertheless, brain damage or death has occasionally resulted from severe hypoglycemia (e.g., Sunny von Bülow
).
, ketone
s). Our knowledge of the "switchover" process is incomplete. The most severe neuroglycopenic symptoms occur with hypoglycemia caused by excess insulin
because insulin
reduces the availability of other fuels by suppressing ketogenesis
and gluconeogenesis
.
A few types of specialized neuron
s, especially in the hypothalamus
, act as glucose sensors, responding to changing levels of glucose by increasing or decreasing their firing rates. They can elicit a variety of hormonal
, autonomic
, and behavioral responses to neuroglycopenia. The hormonal and autonomic responses include release of counterregulatory hormone
s. There is some evidence that the autonomic nervous system can alter liver
glucose metabolism
independently of the counterregulatory hormones.
Adjustment of efficiency of transfer of glucose from blood across the blood-brain barrier
into the central nervous system
represents a third form of compensation which occurs more gradually. Levels of glucose within the central nervous system are normally lower than the blood, regulated by an incompletely understood transfer process. Chronic hypoglycemia or hyperglycemia
seems to result in an increase or decrease in efficiency of transfer to maintain CNS levels of glucose within an optimal range.
In both young and old patients, the brain may habituate to low glucose levels, with a reduction of noticeable symptoms, sometimes despite neuroglycopenic impairment. In insulin-dependent diabetic patients this phenomenon is termed hypoglycemia unawareness and is a significant clinical problem when improved glycemic control is attempted. Another aspect of this phenomenon occurs in type I glycogenosis
, when chronic hypoglycemia before diagnosis may be better tolerated than acute hypoglycemia after treatment is underway.
(CSF), a condition referred to as hypoglycorrhachia [or hypoglycorrhacia].
Hypoglycorrhachia is associated with Glucose transporter type 1 GLUT1
deficiency syndrome (GLUT1DS).
Perhaps a much more common example of the same phenomenon occurs in the people with poorly controlled type 1 diabetes who develop symptoms of hypoglycemia at levels of blood glucose which are normal for most people.
Glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...
(glycopenia) in the brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
, usually due to hypoglycemia
Hypoglycemia
Hypoglycemia or hypoglycæmia is the medical term for a state produced by a lower than normal level of blood glucose. The term literally means "under-sweet blood"...
. Glycopenia affects the function of neurons, and alters brain function and behavior. Prolonged neuroglycopenia can result in permanent damage to the brain.
Signs and symptoms of neuroglycopenia
- Abnormal mentation, impaired judgement
- Nonspecific dysphoriaDysphoriaDysphoria is medically recognized as a mental and emotional condition in which a person experiences intense feelings of depression, discontent and indifference to the world around them.Mood disorders can induce dysphoria, often with a heightened risk of suicide, especially in...
, anxietyAnxietyAnxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...
, moodinessMood swing-Associated disorders:Mood swings are commonly associated with mood disorders including bipolar disorder and depression. In patients with cases of bipolar disorder, the patient experiences serious mood swings that last for days or even weeks...
, depressionDepression (mood)Depression is a state of low mood and aversion to activity that can affect a person's thoughts, behaviour, feelings and physical well-being. Depressed people may feel sad, anxious, empty, hopeless, helpless, worthless, guilty, irritable, or restless...
, crying, fear of dying, suicidal thoughtsSuicidal ideationSuicidal ideation is a common medical term for thoughts about suicide, which may be as detailed as a formulated plan, without the suicidal act itself. Although most people who undergo suicidal ideation do not commit suicide, some go on to make suicide attempts... - Negativism, irritabilityIrritabilityIrritability is an excessive response to stimuli. The term is used for both the physiological reaction to stimuli and for the pathological, abnormal or excessive sensitivity to stimuli; It is usually used to refer to anger or frustration....
, belligerence, combativeness, rageRage (emotion)Rage is a feeling of intense anger. It is associated with the Fight-or-flight response and oftentimes activated in response to an external cue, such as the murder of a loved one. The phrase, 'thrown into a fit of rage,' expresses the immediate nature of rage that occurs before deliberation. If left... - Personality change, emotional lability
- Fatigue, weaknessMuscle weaknessMuscle weakness or myasthenia is a lack of muscle strength. The causes are many and can be divided into conditions that have true or perceived muscle weakness...
, apathyApathyApathy is a state of indifference, or the suppression of emotions such as concern, excitement, motivation and passion. An apathetic individual has an absence of interest in or concern about emotional, social, spiritual, philosophical or physical life.They may lack a sense of purpose or meaning in...
, lethargy, daydreaming, sleepSleepSleep is a naturally recurring state characterized by reduced or absent consciousness, relatively suspended sensory activity, and inactivity of nearly all voluntary muscles. It is distinguished from quiet wakefulness by a decreased ability to react to stimuli, and is more easily reversible than... - ConfusionConFusionConFusion is an annual science fiction convention organized by the Stilyagi Air Corps and its parent organization, the Ann Arbor Science Fiction Association. Commonly, it is held the third weekend of January. It is the oldest science fiction convention in Michigan, a regional, general SF con...
, amnesiaAmnesiaAmnesia is a condition in which one's memory is lost. The causes of amnesia have traditionally been divided into categories. Memory appears to be stored in several parts of the limbic system of the brain, and any condition that interferes with the function of this system can cause amnesia...
, dizzinessDizzinessDizziness refers to an impairment in spatial perception and stability. The term is somewhat imprecise. It can be used to mean vertigo, presyncope, disequilibrium, or a non-specific feeling such as giddiness or foolishness....
, deliriumDeliriumDelirium or acute confusional state is a common and severe neuropsychiatric syndrome with core features of acute onset and fluctuating course, attentional deficits and generalized severe disorganization of behavior... - StaringStaringStaring is a prolonged gaze or fixed look. In staring, one object or person is the continual focus of visual interest, for an amount of time. Staring can be interpreted as being either hostile, or the result of intense concentration or affection. Staring behaviour can be considered a form of...
, "glassy" look, blurred visionBlurred vision-Causes:There are many causes of blurred vision:* Use of atropine or other anticholinergics* Presbyopia -- Difficulty focusing on objects that are close. The elderly are common victims....
, double visionDiplopiaDiplopia, commonly known as double vision, is the simultaneous perception of two images of a single object that may be displaced horizontally, vertically, or diagonally in relation to each other... - Automatic behaviorAutomatic behaviorAutomatic behavior, from the Greek automatos or self-acting, is the spontaneous production of often purposeless verbal or motor behavior without conscious self-control or self-censorship...
- Difficulty speaking, slurred speech
- AtaxiaAtaxiaAtaxia is a neurological sign and symptom that consists of gross lack of coordination of muscle movements. Ataxia is a non-specific clinical manifestation implying dysfunction of the parts of the nervous system that coordinate movement, such as the cerebellum...
, incoordination, sometimes mistaken for "drunkennessDrunkennessAlcohol intoxication is a physiological state that occurs when a person has a high level of ethanol in his or her blood....
" - Focal or general motor deficit, paralysisParalysisParalysis is loss of muscle function for one or more muscles. Paralysis can be accompanied by a loss of feeling in the affected area if there is sensory damage as well as motor. A study conducted by the Christopher & Dana Reeve Foundation, suggests that about 1 in 50 people have been diagnosed...
, hemiparesisHemiparesisHemiparesis is weakness on one side of the body. It is less severe than hemiplegia - the total paralysis of the arm, leg, and trunk on one side of the body. Thus, the patient can move the impaired side of his body, but with reduced muscular strength.... - ParesthesiaParesthesiaParesthesia , spelled "paraesthesia" in British English, is a sensation of tingling, burning, pricking, or numbness of a person's skin with no apparent long-term physical effect. It is more generally known as the feeling of "pins and needles" or of a limb "falling asleep"...
, headacheHeadacheA headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the... - StuporStuporStupor is the lack of critical cognitive function and level of consciousness wherein a sufferer is almost entirely unresponsive and only responds to base stimuli such as pain. This is often mistaken for delirium and treated with Haldol and or other anti-psychotic drugs...
, comaComaIn medicine, a coma is a state of unconsciousness, lasting more than 6 hours in which a person cannot be awakened, fails to respond normally to painful stimuli, light or sound, lacks a normal sleep-wake cycle and does not initiate voluntary actions. A person in a state of coma is described as...
, abnormal breathing - Generalized or focal seizuresFocal seizuresPartial seizures are seizures which affect only a part of the brain at onset. The brain is divided into two hemispheres, each consisting of four lobes - the frontal, temporal, parietal and occipital lobes...
Not all of the above manifestations occur in every case of hypoglycemia. There is no consistent order to the appearance of the symptoms. Specific manifestations vary by age and by the severity of the hypoglycemia. In older children and adults, moderately severe hypoglycemia can resemble mania, mental illness, drug intoxication, or drunkenness. In the elderly, hypoglycemia can produce focal stroke-like effects or a hard-to-define malaise. The symptoms of a single person do tend to be similar from episode to episode.
In the large majority of cases, hypoglycemia severe enough to cause seizures or unconsciousness can be reversed without obvious harm to the brain. Cases of death or permanent neurologic damage occurring with a single episode have usually involved prolonged, untreated unconsciousness, interference with breathing, severe concurrent disease, or some other type of vulnerability. Nevertheless, brain damage or death has occasionally resulted from severe hypoglycemia (e.g., Sunny von Bülow
Sunny von Bülow
Martha Sharp Crawford von Bülow , known as Sunny von Bülow, was an American heiress and socialite. Her husband, Claus von Bülow, was convicted of attempting her murder by insulin overdose, but the conviction was overturned on appeal...
).
Compensatory responses to neuroglycopenia
Most neurons have the ability to use other fuels besides glucose (e.g., lactic acidLactic acid
Lactic acid, also known as milk acid, is a chemical compound that plays a role in various biochemical processes and was first isolated in 1780 by the Swedish chemist Carl Wilhelm Scheele. Lactic acid is a carboxylic acid with the chemical formula C3H6O3...
, ketone
Ketone
In organic chemistry, a ketone is an organic compound with the structure RCR', where R and R' can be a variety of atoms and groups of atoms. It features a carbonyl group bonded to two other carbon atoms. Many ketones are known and many are of great importance in industry and in biology...
s). Our knowledge of the "switchover" process is incomplete. The most severe neuroglycopenic symptoms occur with hypoglycemia caused by excess insulin
Hyperinsulinemic hypoglycemia
Hyperinsulinemic hypoglycemia describes the condition and effects of low blood glucose caused by excessive insulin. Hypoglycemia due to excess insulin is the most common type of serious hypoglycemia. It can be due to endogenous or injected insulin.-Causes:...
because insulin
Insulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
reduces the availability of other fuels by suppressing ketogenesis
Ketogenesis
Ketogenesis is the process by which ketone bodies are produced as a result of fatty acid breakdown.-Production:Ketone bodies are produced mainly in the mitochondria of liver cells. Its synthesis occurs in response to low glucose levels in the blood, and after exhaustion of cellular carbohydrate...
and gluconeogenesis
Gluconeogenesis
Gluconeogenesis is a metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates such as lactate, glycerol, and glucogenic amino acids....
.
A few types of specialized neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
s, especially in the hypothalamus
Hypothalamus
The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...
, act as glucose sensors, responding to changing levels of glucose by increasing or decreasing their firing rates. They can elicit a variety of hormonal
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...
, autonomic
Autonomic nervous system
The autonomic nervous system is the part of the peripheral nervous system that acts as a control system functioning largely below the level of consciousness, and controls visceral functions. The ANS affects heart rate, digestion, respiration rate, salivation, perspiration, diameter of the pupils,...
, and behavioral responses to neuroglycopenia. The hormonal and autonomic responses include release of counterregulatory hormone
Counterregulatory hormone
A counterregulatory hormone is a hormone that opposes the action of another.The action of insulin is counterregulated by glucagon, adrenaline , noradrenaline , cortisol, and growth hormone...
s. There is some evidence that the autonomic nervous system can alter liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
glucose metabolism
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...
independently of the counterregulatory hormones.
Adjustment of efficiency of transfer of glucose from blood across the blood-brain barrier
Blood-brain barrier
The blood–brain barrier is a separation of circulating blood and the brain extracellular fluid in the central nervous system . It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion...
into the central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
represents a third form of compensation which occurs more gradually. Levels of glucose within the central nervous system are normally lower than the blood, regulated by an incompletely understood transfer process. Chronic hypoglycemia or hyperglycemia
Hyperglycemia
Hyperglycemia or Hyperglycæmia, or high blood sugar, is a condition in which an excessive amount of glucose circulates in the blood plasma. This is generally a glucose level higher than 13.5mmol/l , but symptoms may not start to become noticeable until even higher values such as 15-20 mmol/l...
seems to result in an increase or decrease in efficiency of transfer to maintain CNS levels of glucose within an optimal range.
In both young and old patients, the brain may habituate to low glucose levels, with a reduction of noticeable symptoms, sometimes despite neuroglycopenic impairment. In insulin-dependent diabetic patients this phenomenon is termed hypoglycemia unawareness and is a significant clinical problem when improved glycemic control is attempted. Another aspect of this phenomenon occurs in type I glycogenosis
Glycogen storage disease
Glycogen storage disease is the result of defects in the processing of glycogen synthesis or breakdown within muscles, liver, and other cell types. GSD has two classes of cause: genetic and acquired. Genetic GSD is caused by any inborn error of metabolism involved in these processes...
, when chronic hypoglycemia before diagnosis may be better tolerated than acute hypoglycemia after treatment is underway.
Neuroglycopenia without hypoglycemia
A rare metabolic disease of the blood-brain glucose transport system has been described in which severe neuroglycopenic effects occurred despite normal blood glucose levels. Low levels of glucose were discovered in the cerebrospinal fluidCerebrospinal fluid
Cerebrospinal fluid , Liquor cerebrospinalis, is a clear, colorless, bodily fluid, that occupies the subarachnoid space and the ventricular system around and inside the brain and spinal cord...
(CSF), a condition referred to as hypoglycorrhachia [or hypoglycorrhacia].
Hypoglycorrhachia is associated with Glucose transporter type 1 GLUT1
GLUT1
Glucose transporter 1 , also known as solute carrier family 2, facilitated glucose transporter member 1 is a protein that in humans is encoded by the SLC2A1 gene...
deficiency syndrome (GLUT1DS).
Perhaps a much more common example of the same phenomenon occurs in the people with poorly controlled type 1 diabetes who develop symptoms of hypoglycemia at levels of blood glucose which are normal for most people.