Central pontine myelinolysis

From Wikipedia, the free encyclopedia
Jump to: navigation, search
Central pontine myelinolysis
Classification and external resources
Illu pituitary pineal glands.jpg
Pons labeled at bottom left
ICD-10 G37.2
DiseasesDB 2198
MedlinePlus 000775
eMedicine neuro/50
MeSH D017590
Central pontine myelinolysis, MRI FLAIR
Axial fat-saturated T2-weighted image showing hyperintensity in the pons with sparing of the peripheral fibers, the patient was an alcoholic admitted with a serum Na of 101 treated with hypertonic saline, he was left with quadreparesis, dysarthria, and altered mental status

Central pontine myelinolysis (CPM), also known as Osmotic demyelination syndrome, is a neurological disease caused by severe damage of the myelin sheath of nerve cells in the brainstem, more precisely in the area termed the pons, predominately of iatrogenic etiology. It is characterized by acute paralysis, dysphagia (difficulty swallowing), and dysarthria (difficulty speaking), and other neurological symptoms.

It can also occur outside the pons.[1] The term "osmotic demyelination syndrome" is similar to "central pontine myelinolysis", but also includes areas outside the pons.[2]

Central pontine myelinolysis presents most commonly as a complication of treatment of patients with profound, life-threatening hyponatremia (low sodium). It occurs as a consequence of a rapid rise in serum tonicity following treatment in individuals with chronic, severe hyponatraemia who have made intracellular adaptations to the prevailing hypotonicity.[3] Hyponatremia should be corrected at a rate of no more than 12-20 mmol/L of sodium per day to prevent central pontine myelinolysis.[3]

Although less common, it may also present in patients with a history of chronic alcoholism or other conditions related to decreased liver function. In these cases, the condition is often unrelated to correction of sodium or electrolyte imbalance.

Pathophysiology[edit]

The currently accepted theory states that the brain cells adjust their osmolarities by changing levels of certain osmolytes like inositol, betaine, and glutamine. In hyponatremia the levels of these osmolytes fall, causing the cells to absorb free-water. The reverse is true for hypernatremia, in which cells will shrink to dilute the hypernatremic fluid. So rapid correction of sodium in hyponatremia would cause the extracellular fluid to be relatively hypertonic. Free water would then move out of the cells to decrease this relative hypertonicity. This leads to a central pontine myelinolysis, manifesting as the paralysis. The brain appears to shrink.

The demyelination of the axons (nerve fibers in the brain) damages them.[4]

In the context of chronic low plasma sodium, the brain's cells (neurons and glia) adapt by taking in a small amount of water; the net effect is to move water out of the interstitium and equilibrate (or nearly so) the intracellular and extracellular tonicities. The chronic hyponatremia is thus compensated.

With correction of the hyponatremia with intravenous fluids, the intra- and extra-cellular tonicities are again changed, this time in the opposite direction. With the use of intravenous hypertonic saline, the correction can be too quick, not allowing enough time for the brain's cells to adjust to the new tonicity. With a rise in extracellular tonicity, the cells compensate by losing a small amount of water. This loss will continue until the intra- and extra-cellular tonicities are equal. If hypertonic therapy continues or is too rapid, the extracellular tonicity will continue to drive water out of the brain's cells, leading to cellular dysfunction and the condition of central pontine myelinolysis.

Rapid correction of hypernatremia causes water to move into cells, leading to multiple cerebral hemorrhages, which is as catastrophic as osmotic demyelination.

Causes[edit]

Loss of myelinated fibers at the basis pontis in the brainstem (Luxol-Fast blue stain)

The most common cause is the too rapid correction of low blood sodium levels (hyponatremia).[5]

It has also been known to occur in patients suffering withdrawal symptoms of chronic alcoholism.[6] In these instances, occurrence may be entirely unrelated to hyponatremia or rapid correction of hyponatremia.

It has been observed following hematopoietic stem cell transplantation.[7]

CPM may also occur in patients affected by

Diagnosis[edit]

It can be difficult to identify using conventional imaging techniques. It presents more prominently on MRI than on CT, often taking several weeks after acute onset of symptoms before it becomes identifiable. Imaging by MRI demonstrates an area of high signal return on T2 weighted images.

Symptoms[edit]

T2 weighted magnetic resonance scan image showing bilaterally symmetrical hyperintensities in Caudate nucleus (small, thin arrow), Putamen (long arrow), with sparing of Globus Pallidus (broad arrow), suggestive of Extrapontine myelinolysis.

Clinical presentation of CPM is heterogeneous and depend on the regions of the brain involved. Observable immediate precursors may include seizures, disturbed consciousness, gait changes, and decrease or cessation of respiratory function.[19][20]

Frequently observed symptoms in this disorder are acute para- or quadraparesis, dysphagia, dysarthria, diplopia, loss of consciousness, and other neurological symptoms associated with brainstem damage. The patient may experience locked-in syndrome where cognitive function is intact, but all muscles are paralyzed with the exception of eye blinking. These result from a rapid myelinolysis of the corticobulbar and corticospinal tracts in the brainstem.[21]

Prevention and treatment[edit]

To prevent CPM from its most common cause, overly rapid reversal of hyponatremia, the hyponatremia should be corrected at a rate not exceeding 10 mmol/L/24 h or 0.5 mEq/L/h; thus avoiding hypernatremia.[3] Details concerning the etiology and correction of electrolyte disorders are discussed extensively in general medicine texts. Alcoholic patients should receive vitamin supplementation and a formal evaluation of their nutritional status.[22][23]

Once demyelination of the pons has begun, there is no cure or specific treatment. Care is supportive, with the goal of preventing complications like aspiration pneumonia or deep vein thrombosis. Alcoholics are usually given vitamins to correct for other deficiencies.

Research has led to improved outcomes.[24] Animal studies suggest that inositol reduces the severity of osmotic demyelination syndrome if given before attempting to correct chronic hyponatraemia.[25] Further study is required before using inositol in humans for this purpose.

Prognosis[edit]

The prognosis is overall poor. However, recent data indicate that the prognosis of critically ill patients may even be better than what is generally considered,[26] despite severe initial clinical manifestations and a tendency by the intensivists to underestimate a possible favorable evolution.[27] While some patients die, most survive and of the survivors, approximately one-third recover; one-third are disabled but are able to live independently; one-third are severely disabled.[28] Permanent disabilities range from minor tremors and ataxia to signs of severe brain damage, such as spastic quadriparesis and locked-in syndrome.[29] Some improvements may be seen over the course of the first several months after the condition stabilizes.

The extent of recovery depends on how many axons were damaged.[4]

References[edit]

  1. ^ Gocht A, Colmant HJ (1987). "Central pontine and extrapontine myelinolysis: a report of 58 cases". Clin. Neuropathol. 6 (6): 262–70. PMID 3322623. 
  2. ^ Lampl C, Yazdi K (2002). "Central pontine myelinolysis". Eur. Neurol. 47 (1): 3–10. doi:10.1159/000047939. PMID 11803185. Archived from the original on 2010-11-18. 
  3. ^ a b c Babar, S. (October 2013). "SIADH Associated With Ciprofloxacin.". Annals of Pharmacotherapy (Sage Publishing) 47 (10): 1359–1363. doi:10.1177/1060028013502457. ISSN 1060-0280. PMID 24259701. Retrieved November 18, 2013. 
  4. ^ a b Medana IM, Esiri MM (March 2003). "Axonal damage: a key predictor of outcome in human CNS diseases". Brain 126 (Pt 3): 515–30. doi:10.1093/brain/awg061. PMID 12566274. 
  5. ^ Bernsen HJ, Prick MJ (September 1999). "Improvement of central pontine myelinolysis as demonstrated by repeated magnetic resonance imaging in a patient without evidence of hyponatremia". Acta Neurol Belg 99 (3): 189–93. PMID 10544728. 
  6. ^ Yoon B, Shim YS, Chung SW (2008). "Central Pontine and Extrapontine Myelinolysis After Alcohol Withdrawal". Alcohol 43 (6): 647–9. doi:10.1093/alcalc/agn050. 
  7. ^ Lim KH, Kim S, Lee YS, et al. (April 2008). "Central pontine myelinolysis in a patient with acute lymphoblastic leukemia after hematopoietic stem cell transplantation: a case report". J. Korean Med. Sci. 23 (2): 324–7. doi:10.3346/jkms.2008.23.2.324. PMC 2526450. PMID 18437020. [dead link]
  8. ^ Singh N, Yu VL, Gayowski T (March 1994). "Central nervous system lesions in adult liver transplant recipients: clinical review with implications for management". Medicine (Baltimore) 73 (2): 110–8. PMID 8152365. 
  9. ^ Kato T, Hattori H, Nagato M, Kiuchi T, Uemoto S, Nakahata T, Tanaka K (April 2002). "Subclinical central pontine myelinolysis following liver transplantation". Brain Dev. 24 (3): 179–82. PMID 11934516. Retrieved 2014-05-29. 
  10. ^ Martinez AJ, Estol C, Faris AA (May 1988). "Neurologic complications of liver transplantation". Neurol Clin 6 (2): 327–48. PMID 3047544. 
  11. ^ McKee AC, Winkelman MD, Banker BQ (August 1988). "Central pontine myelinolysis in severely burned patients: relationship to serum hyperosmolality". Neurology 38 (8): 1211–7. PMID 3399069. 
  12. ^ Winkelman MD, Galloway PG (September 1992). "Central nervous system complications of thermal burns. A postmortem study of 139 patients". Medicine (Baltimore) 71 (5): 271–83. PMID 1522803. 
  13. ^ Sugimoto T, Murata T, Omori M, Wada Y (March 2003). "Central pontine myelinolysis associated with hypokalaemia in anorexia nervosa". J. Neurol. Neurosurg. Psychiatr. 74 (3): 353–5. PMC 1738317. PMID 12588925. Retrieved 2014-05-29. 
  14. ^ Keswani SC (April 2004). "Central pontine myelinolysis associated with hypokalaemia in anorexia nervosa". J. Neurol. Neurosurg. Psychiatr. 75 (4): 663; author reply 663. PMC 1739009. PMID 15026526. Retrieved 2014-05-29. 
  15. ^ Leroy S, Gout A, Husson B, de Tournemire R, Tardieu M (June 2012). "Centropontine myelinolysis related to refeeding syndrome in an adolescent suffering from anorexia nervosa". Neuropediatrics 43 (3): 152–4. doi:10.1055/s-0032-1307458. PMID 22473289. Retrieved 2014-05-29. 
  16. ^ Bergin PS, Harvey P (August 1992). "Wernicke's encephalopathy and central pontine myelinolysis associated with hyperemesis gravidarum". BMJ 305 (6852): 517–8. PMC 1882865. PMID 1393001. Retrieved 2014-05-29. 
  17. ^ Sutamnartpong P, Muengtaweepongsa S, Kulkantrakorn K (January 2013). "Wernicke's encephalopathy and central pontine myelinolysis in hyperemesis gravidarum". J Neurosci Rural Pract 4 (1): 39–41. doi:10.4103/0976-3147.105608. PMC 3579041. PMID 23546346. Retrieved 2014-05-29. 
  18. ^ Kishimoto Y, Ikeda K, Murata K, Kawabe K, Hirayama T, Iwasaki Y (2012). "Rapid development of central pontine myelinolysis after recovery from Wernicke encephalopathy: a non-alcoholic case without hyponatremia". Intern. Med. 51 (12): 1599–603. PMID 22728498. Retrieved 2014-05-29. 
  19. ^ Musana AK, Yale SH (August 2005). "Central pontine myelinolysis: case series and review". WMJ 104 (6): 56–60. PMID 16218318. 
  20. ^ Odier C, Nguyen DK, Panisset M (July 2010). "Central pontine and extrapontine myelinolysis: from epileptic and other manifestations to cognitive prognosis". J. Neurol. 257 (7): 1176–80. doi:10.1007/s00415-010-5486-7. PMID 20148334. 
  21. ^ Karp BI, Laureno R (November 1993). "Pontine and extrapontine myelinolysis: a neurologic disorder following rapid correction of hyponatremia". Medicine (Baltimore) 72 (6): 359–73. PMID 8231786. 
  22. ^ Kleinschmidt-DeMasters BK, Norenberg MD (March 1981). "Rapid correction of hyponatremia causes demyelination: relation to central pontine myelinolysis". Science 211 (4486): 1068–70. doi:10.1126/science.7466381. PMID 7466381. 
  23. ^ Laureno R (1980). "Experimental pontine and extrapontine myelinolysis". Trans Am Neurol Assoc 105: 354–8. PMID 7348981. 
  24. ^ Brown WD (December 2000). "Osmotic demyelination disorders: central pontine and extrapontine myelinolysis". Curr. Opin. Neurol. 13 (6): 691–7. doi:10.1097/00019052-200012000-00014. PMID 11148672. 
  25. ^ Silver SM, Schroeder BM, Sterns RH, Rojiani AM (2006). "Myoinositol administration improves survival and reduces myelinolysis after rapid correction of chronic hyponatremia in rats". J Neuropathol Exp Neurol 65 (1): 37–44. doi:10.1097/01.jnen.0000195938.02292.39. PMID 16410747. 
  26. ^ Louis G, Megarbane B, Lavoué S, Lassalle V, Argaud L, Poussel JF, Georges H, Bollaert PE (March 2012). "Long-term outcome of patients hospitalized in intensive care units with central or extrapontine myelinolysis*". Critical Care Medicine 40 (3): 970–2. doi:10.1097/CCM.0b013e318236f152. PMID 22036854. Retrieved 2014-05-30. 
  27. ^ Young GB (March 2012). "Central pontine myelinolysis: a lesson in humility*". Critical Care Medicine 40 (3): 1026–7. doi:10.1097/CCM.0b013e31823b8e0b. PMID 22343870. Retrieved 2014-05-30. 
  28. ^ Abbott R, Silber E, Felber J, Ekpo E (October 2005). "Osmotic demyelination syndrome". BMJ 331 (7520): 829–30. doi:10.1136/bmj.331.7520.829. PMC 1246086. PMID 16210283. 
  29. ^ http://www.emedicine.com/NEURO/topic50.htm

External links[edit]

  • MedPix Images of Osmotic Myelinolysis