osmotic demyelination syndrome clinical scenario

Discussion on osmotic demyelination syndrome clinical scenario for residents.

1. O smotic D emyelination S yndrome Dr. CHIRAYU REGMI MD, INTERNAL MEDICINE Resident, Neurology UDM- NINAS

2. INTRODUCTION   The serum sodium concentration is the primary determinant of serum tonicity The neurologic manifestations associated with overly rapid correction have been called the osmotic demyelination syndrome almost all patients who develop ODS present with a serum sodium concentration of 120  mEq /L or less.

3. BRAIN ADAPTATION TO HYPONATREMIA   A decrease in serum tonicity causes water to flow across the blood-brain barrier, increasing brain water content . T his causes brain cells to swell. The brain begins to adapt to hypotonicity almost immediately after a fall in serum sodium A daptation is complete within two days.

4. In addition, cells begin to lose intracellular solutes, principally potassium and organic solutes . This process permits these cells to shed excess water and to have the same tonicity as plasma without a large increase in cell water

5. O nce the brain has adapted to hypotonicity , the rate of correction of the hyponatremia becomes important. R apid correction is  not  likely to induce ODS in patients with severe hyponatremia that has only been present for several hours since the cerebral adaptation is at an early stage.

6. Demyelination primarily occurs in areas of the brain that are slowest in re-accumulating osmolytes after rapid correction of hyponatremia Demyelination of the central pons is one manifestation of ODS. brain demyelination may be more diffuse, and it does not always involve the pons

7. RISK FACTORS FOR ODS     The ODS primarily occurs with overly rapid correction of severe hyponatremia that has been present for more than two to three days. some patients are particularly susceptible to this complication and can develop ODS with less severe hyponatremia.

8. Serum sodium at presentation   M ajority of reported cases - serum sodium of 120  mEq /L or less. more severe hyponatremia at presentation tend to experience a larger increase in the serum sodium concentration during treatment Cerebral adaptation - greater depletion of brain organic osmolytes T hese patients are also more likely to develop ODS after rapid correction.

9. Duration of hyponatremia   brain damage does not occur when hyponatremia of less than one day's duration is rapidly corrected. the brain does not have time to fully adapt . if hyponatremia persists for two to three days or more, the same treatment results in usually fatal demyelinating brain lesions. clinicians should assume that the patient has chronic hyponatremia unless the history suggests otherwise

10. Overly rapid rate of correction     osmotic demyelination is caused by correction of hyponatremia and not by hyponatremia itself . more rapid rates of correction increase the likelihood and severity of brain lesions.

11. M ore rapid hourly rate of correction is associated with more severe lesions only if the daily rate threshold is exceeded. if the daily rate of correction remains lower than the threshold for inducing osmotic demyelination recommendations on the rate of correction of hyponatremia are based upon the daily, rather than the hourly rate of correction.

12. rate of correction of hyponatremia should not exceed 6 to 8  mEq /L in any 24-hour period. This is not a goal of therapy, but rather a therapeutic limit that should not be exceeded.

13. Causes of overly rapid correction   following therapy that is specifically directed at raising the sodium concentration (such as hypertonic saline or initiation of a vasopressin antagonist) and following cessation of a reversible stimulus to ADH release cessation of exogenous desmopressin therapy.

14. Auto correction of the serum sodium The administration of saline to patients with true volume depletion. Restoration of euvolemia rapidly suppresses the release of ADH thereby allowing excretion of the excess water. The administration of glucocorticoids to patients with adrenal insufficiency Discontinuation of drugs SIADH(SSRI,   carbamazepine,desmopressin )

15. Discontinuation of thiazide diuretics since they interfere with urinary dilution Spontaneous resolution of a transient cause for SIADH ( eg , surgical stress, nausea, pneumonia). Treatment with a vasopressin receptor antagonist.

16. Auto-correction of a reversible impairment in water excretion is an important reason why equations that are used to calculate the serum sodium response to a given fluid regimen frequently fail to predict the actual response.

17. Other Alcoholism malnutrition liver disease hypokalemia Women of childbearing age. No gender predilection.

18. Lesions of CPM and EPM Pons Cerebellum Lateral geniculate body External capsule Hippocampus Putamen Cerebral cortex / subcortex Thalamus Caudate nucleus

19. The following 10% or less: Claustrum Internal capsule Midbrain Internal medullary lamella Mamillary body Medulla oblongata

20. OSMOTIC DEMYELINATION SYNDROMES Central pontine myelinolysis (CPM ) typically  delayed  for two to six days The initial signs- dysarthria and dysphagia. a flaccid quadriparesis which later becomes spastic. if the lesion extends into the tegmentum of the pons- pupillary , oculomotor abnormalities may occur.

21. Corticospinal signs (hyperreflexia and bilateral Babinski signs) and corticobulbar signs (brisk jaw jerk) are common. Other common physical findings- increased muscle tone facial weaknes , grasp or rooting reflexes.

22. In patients with pontine involvement, speech abnormalities occur early and persist, and patients often become mute. Swallowing dysfunction- aspiration pneumonia and respiratory failure . There may be an apparent change in conscious level reflecting the ‘‘locked-in syndrome’’ .

23. Extrapontine involvement If lesions of EPM are also present the clinical picture can be confusing The manifestations can be early onset or can be delayed from 10 days-6 months.

24. Diagnosis ODS should be suspected in all patients overly rapid correction of hyponatremia who have risk factors for the disorder consistent clinical manifestations

25. MR imaging the classic trident-shaped abnormality. Seen in axial images. The outer rim of the pons is typically normal.

26. Imaging MRI may not become positive for as long as four weeks after disease onset Initially negative radiologic study does  not  exclude ODS R epeat MRI should be obtained after 2 to 4 weeks.

27. PREVENTION OF ODS Differentiation of acute from chronic hyponatremia Patients with severe hyponatremia of less than 48 hours duration (acute hyponatremia ) usually present with neurological symptoms they respond to a bolus or more of hypertonic (3%) saline that are capable of producing rapid controlled rises of their serum sodium . they tolerate the controlled rapid rises of serum sodium and their risk of ODS low

28. Patients with chronic hyponatremia are presumed to have already developed the process of adaptation. Caution should be taken while attempting to raise the serum sodium of chronic hyponatremia patients. Whenever uncertainty exists about the duration of hyponatremia, it is prudent to consider it chronic.

29. The method used to raise serum sodium : conservative measures should be initiated with withdrawing an offending medication Fluid restriction be tried in cases of SIADH. Hypertonic saline is usually reserved for patients with severe chronic hyponatremia with severe neurological symptoms(convulsions and coma) in patients with moderate neurological symptoms that are persistent or progressive in spite of the conservative measures .

30. Isotonic saline (0.9% saline) infusion is usually indicated for the treatment of hypovolemic hyponatremia. keep in mind that isotonic saline infusion may cause an overly rapid correction of plasma sodium with ODS as a possible consequence. Treating chronic hyponatremia patients with isotonic saline should be associated with as much caution as with hypertonic saline.

31. Target and rate of serum sodium rise: C hronic hyponatremia and severe neurological symptoms An increase in serum sodium of 2-4 mmol /L in 2-4 hours may be beneficial with low risk of ODS. followed by caution not to exceed the total of 6-8 mmol /L in 24 hours This rapid controlled rise is usually achieved with a bolus or two of 100 ml of 3% saline. Restrict- increase in [Na] to < 6-8 mmol /L in the first 24 h and < 16 mmol /L in the first 48 h

32. Management of chronic hyponatremia without severe symptoms it is advocated to adopt a cautious approach and limit the correction to 6-8 mmol /L in the first 24 hours 12-14 mmol /L in the first 48 hours.

33. Extra caution with high risk patients Patients at high risk- alcohol abuse, concomitant hypokalemia, malnutrition , liver disease the conservative measures-water restriction,stopping the offending drug should be given the chance before implementation of more active measures, especially in absence of severe symptoms.

34. A controlled correction of hyponatremia with desmopressin prophylaxis may be considered In cases of concomitant hypokalemia, the administration of potassium may raise the serum sodium and osmolality. slower rates of correction and lower targets of serum sodium should be considered in the presence of vigilant monitoring .

35. Monitoring: There no way to precisely predict the rise in serum sodium in response to a given rate of infusion of isotonic or hypertonic saline. monitoring is of utmost importance. Monitoring helps to anticipate or early-detect the inadvertent rise in serum sodium Monitoring of serum sodium should be carried out every 2-4 hours.

36. Monitoring of urine output and urine osmolality. a rise in urine output of 100 ml/hour-signals increased risk of overly rapid rise in serum sodium concentration and warrants measuring urine osmolality.

37. Treatment of established ODS    T ypically require intensive supportive therapy. In addition, such patients should have their serum sodium re lowered.

38. Relowering the serum sodium to treat ODS  —  Re-lowering the serum sodium to a level that is  just below the maximal 48-hour target value (less tha 16  mEq /L above the initial serum sodium ) The concurrent administration of desmopressin and 5% dextrose (D5W) in water can be given.

39. DOSES D5W , 6 mL/kg  infused over two hours. This quantity of D5W should lower the serum sodium by approximately 2  mEq /L T he infusion should be repeated until the therapeutic goal. Desmopressin - 2 mcg i /v or s/c every six hours the dose can be increased to 4 mcg in rare patients.

40. A fter the onset of neurologic symptoms that are attributed to ODS Re-lowering therapy should be initiated as quickly as possible The patient's neurologic status and serum sodium – monitored.

41. M ovement disorders of EPM R epresent a treatable manifestation P arkinsonism , dystonia, and catatonia have all been described . symptomatic improvement can occur with dopaminergic treatment in those with parkinsonian features .

42. Parkinsonism resulting from acute ODS shows a good response to levodopa Delayed movement disorders respond poorly to drug treatment Levodopa is thought to alleviate symptoms by activating the remaining dopamine receptors in the striatum. Dopamine agonists like pramipexole are also reported to benefit patients with EPM.

43. Supportive therapy    Some patients with ODS recover function after prolonged periods of severe neurologic impairment. aggressive supportive therapy should be provided to all patients. patients with severe ODS frequently develop aspiration pneumonia and respiratory failure, endotracheal intubation and ventilator support are often required.

44. Recovery from seemingly hopeless neurologic deficits can occur Supportive therapy should be continued for at least six to eight weeks before concluding that the deficits are irreversible. The initial severity of the illness is not predictive of long-term prognosis.

45. Immunomodulatory therapy There are no existing guidelines or evidence to suggest the use of immunomodulatory treatment in ODS Small case series or case reports have shown a beneficial effect of various treatment modalities such as methylprednisolone, intravenous immunoglobulin and plasmapheresis

46. Investigational therapies   Minocycline given concurrently with hypertonic saline and/or within 24 hours of the correction of the hyponatremia reduced the severity of neurologic symptoms and histologic demyelination. Minocycline crosses the blood-brain barrier and inhibits microglial activation

47. Reducing microglial production of inflammatory cytokines Has neuroprotective effects in experimental models. There are no available data on minocycline use in humans with overly rapid correction of hyponatremia.

48. A dministration of  myoinositol A t the same time that the serum sodium concentration is rapidly increased. Exogenous administration of myo -inositol rapidly restores the brain myo -inositol content to normal levels There are no data on the use of myoinositol in humans

49. CONCLUSION ODS is a central nervous disorder that is related to rapid correction of chronic hyponatremia. The extent of serum sodium elevation should be limited to 4-6 mmol /L in the first 24 hours and 12-14 mmol /L in the first 48 hours. Frequent periodic monitoring of serum sodium, urine output , and urine osmolality should be done . prevention is the key.

50. THANK YOU