Hypoglycemic Encephalopathy.pptx

ppt

1. Hypoglycemic Encephalopathy Zeleke................NR3

2. Introduction This condition is now relatively infrequent but is an important cause of confusion, convulsions, stupor, and coma; as such, it merits separate consideration as a metabolic disorder of the brain. The essential biochemical abnormality is a critical lowering of the blood glucose.

3. Contd.... At a level of about 30 mg/ dL, the cerebral disorder takes the form of a confusional state and one or more seizures may occu. At a level of 10 mg/dL, there is coma that may result in irreparable injury to the brain if not corrected immediately by the administration of glucose. As with most other metabolic encephalopathies, the rate of decline of blood glucose is a factor in both the depression of consciousness and residual dementia.

4. Contd.... The normal brain has a glucose reserve of 1 to 2 g (30 mmol/100 g of tissue), mostly in the form of glycogen. Because glucose is utilized by the brain at a rate of 60 to 80 mg/min, the glucose reserve may sustain cerebral activity for 30 min or less once blood glucose is no longer available.

5. Contd.... Glucose is transported from the blood to the brain by an active carrier system. Glucose entering the brain either undergoes glycolysis or is stored as glycogen. During normal oxygenation (aerobic metabolism), glucose is converted to pyruvate, which enters the Krebs cycle; with anaerobic metabolism, lactate is formed.

6. Contd.... The oxidation of 1 mole of glucose requires 6 mole of 02. Of the glucose taken up by the brain, 85 to 90 percent is oxidized; the remainder is used in the formation of proteins and other substances, notably neurotransmitters and particularly GABA.

7. Contd.... When blood glucose falls, the CNS can utilize nonglucose substrates to a variable extent for its metabolic needs, especially keto acids and intermediates of glucose metabolism, such as lactate, pyruvate, fructose, and other hexoses.

8. Contd.... In the neonatal brain, which has a higher glycogen reserve, keto acids provide a considerable proportion of cerebral energy requirements; this also happens after prolonged starvation. However, in the face of severe and sustained hypoglycemia, these alternative substrates are inadequate to preserve the structural integrity of neurons, and eventually ATP is depleted as well.

9. Contd.... If convulsions occur, they usually do so during a period of confusion; the convulsions have been attributed to an altered integrity of neuronal membranes and to elevated NH3 and depressed GABA and lactate levels.

10. Contd.... The brain is the only organ besides the heart that suffers severe functional and structural impairment under conditions of severe hypoglycemia. Beyond what is described above, the pathophysiology of the cerebral disorder has not been fully elucidated.

11. Contd.... It is known that hypoglycemia reduces 02 uptake and increases cerebral blood flow. As with anoxia and ischemia, there is experimental evidence that the excitatory amino acid glutamate is involved in the process.

12. Contd.... The levels of several brain phospholipid fractions decrease when animals are given large doses of insulin. However, the suggestion that hypoglycemia results in a rapid depletion and inadequate production of high-energy phosphate compounds has not been corroborated; some other glucose-dependent biochemical processes must be implicated.

13. Etiology The most common causes of hypoglycemic encephalopathy are: accidental or deliberate overdose of insulin or an oral diabetic agent islet cell insulin-secreting tumor of the pancreas depletion of liver glycogen, which occasionally follows a prolonged alcoholic binge, starvation, or any form of severe liver failure glycogen storage disease of infancy;

14. Contd.... an idiopathic hypoglycemia in the neonatal period and infancy subacute and chronic hypoglycemia from islet cell hypertrophy and islet cell tumors of the pancreas, carcinoma of the stomach, fibrous mesothelioma, carcinoma of the cecum, and hepatoma. Purportedly, an insulin-like substance is elaborated by these nonpancreatic tumors.

15. Contd.... In functional hyperinsulinism, as occurs in anorexia nervosa and dietary faddism, the hypoglycemia is rarely of sufficient severity or duration to damage the CNS.

16. Clinical Features The initial symptoms appear when the blood glucose has descended to about 30 mg/dL, nervousness, hunger, flushed facies, sweating, headache, palpitation, trembling, and anxiety. These gradually give way to confusion and drowsiness or occasionally, to excitement, overactivity, and bizarre or combative behavior.

17. Contd.... Many of the early symptoms relate to adrenal and sympathetic overactivity and some of the manifestations may be muted in diabetic patients with neuropathy. In the next stage, forced sucking, grasping, motor restlessness, muscular spasms, and decerebrate rigidity occur, in that sequence.

18. Contd.... Myoclonic twitching and convulsions develop in some patients. Rarely, there are focal cerebral deficits, the pathogenesis of which remains unexplained; according to Malouf and Brust, hemiplegia, corrected by intravenous glucose, was observed in 3 of 125 patients who presented with symptomatic hypoglycemia.

19. Contd.... Blood glucose levels of approximately 10 mg/dL are associated with deep coma, dilatation of pupils, pale skin, shallow respiration, slow pulse and hypotonia, what had in the past been termed the "medullary phase" of hypoglycemia.

20. Contd.... If glucose is administered before this level has been attained, the patient can be restored to normal, retracing the aforementioned steps in reverse order. However, once this state is reached, and particularly if it persists for more than a few minutes, recovery is delayed for a period of days or weeks and may be incomplete as noted below.

21. Contd.... The EEG is altered as the blood glucose falls, but the correlations are imprecise. There is diffuse slowing in the theta or delta range. During recovery, sharp waves may appear and coincide in some cases with seizures.

22. Contd.... The major clinical differences between hypoglycemic and hypoxic encephalopathy lie in the setting and the mode of evolution of the neurologic disorder. The effects of hypoglycemia usually unfold more slowly, over a period of 30 to 60 min, rather than in a few seconds or minutes. The recovery phase and sequelae of the 2 conditions are quite similar.

23. Contd.... A large dose of insulin, which produces intense hypoglycemia, even of relatively brief duration (30 to 60 min), is more dangerous than a series of less-severe hypoglycemic episodes from smaller doses of insulin, possibly because the former impairs or exhausts essential enzymes, a condition that cannot then be overcome by large quantities of intravenous glucose.

24. Contd.... Reflecting the benignity of repeated minor occurrences, the Epidemiology of Diabetes Interventions and Complications Study Research Group have demonstrated that recurrent hypoglycemic episodes in the course of treatment of diabetes over many years are very well tolerated and do not lead to cognitive decline.

25. Contd.... A severe and prolonged episode of hypoglycemia may result in permanent impairment of intellectual function as well as other neurologic residua, like those that follow severe anoxia. We also have observed states of protracted coma, as well as relatively pure Korsakoff amnesia. However, one should not be hasty in prognosis, for we have observed slow improvement to continue for 1 to 2 years.

26. Contd.... Recurrent hypoglycemia from an islet cell tumor may masquerade for some time as an episodic confusional psychosis or convulsive illness; diagnosis then awaits the demonstration of low blood glucose or hyperinsulinism in association with the neurologic symptoms. We saw a man in the emergency department whose main complaint was episodic inability to dial a touchtone telephone and a mild mental fogginess; he was found to have an insulinoma.

27. Contd.... Functional or reactive hypoglycemia is the most ambiguous of all syndromes related to low blood glucose. This condition is usually idiopathic but may precede the onset of diabetes mellitus. The rise of insulin in response to a carbohydrate meal is delayed but then causes an excessive fall in blood glucose, to 30 to 40 mg/ dL.

28. Contd.... The symptoms are malaise, fatigue, nervousness, headache and tremor, which may be difficult to distinguish from anxious depression. Not surprisingly, the term functional hypoglycemia has been much abused, being applied indiscriminately to a variety of complaints that would now be called chronic fatigue syndrome or an anxiety syndrome.

29. Contd.... In fact, a syndrome attributable to functional or reactive hypoglycemia is infrequent and its diagnosis requires the finding of an excessive reaction to insulin, low blood glucose during the symptomatic period, and a salutary response to oral glucose.

30. Contd.... In all forms of hypoglycemic encephalopathy, the major damage is to the cerebral cortex. Cortical nerve cells degenerate and are replaced by microglia cells and astrocytes. The distribution of lesions is similar, although probably not identical to that in hypoxic encephalopathy.

31. Contd.... The cerebellar cortex is less vulnerable to hypoglycemia than to hypoxia.

32. Contd.... Auer has described the ultrastructural changes in neurons resulting from experimental hypoglycemia; with increasing duration of hypoglycemia and EEG silence, there are mitochondrial changes, first in dendrites and then in nerve cell soma, followed by nuclear membrane disruption leading to cell death.

33. Contd.... Severe hypoglycemic cerebral injury causes MRI abnormalities localized to the ( particularily vulnerability areas ): basal ganglia cerebral cortex substantia nigra, and hippocampus

34. Treatment Treatment of all forms of hypoglycemia obviously consists of correction of the hypoglycemia at the earliest possible moment. It is not known whether hypothermia or other measures will increase the safety period in hypoglycemia or alter the outcome. Seizures and twitching may not stop with antiepileptic drugs until the hypoglycemia is corrected.

35. Reference Adams and Victory