Central pontine myelinolysis explained

Central pontine myelinolysis
Synonyms:Osmotic demyelination syndrome, central pontine demyelination
Field:Neurology
Causes:Alcoholism, malnutrition

Central pontine myelinolysis is a neurological condition involving severe damage to the myelin sheath of nerve cells in the pons (an area of the brainstem). It is predominately iatrogenic (treatment-induced), and is characterized by acute paralysis, dysphagia (difficulty swallowing), dysarthria (difficulty speaking), and other neurological symptoms.

Central pontine myelinolysis was first described as a disorder in 1959. The original paper[1] described four cases with fatal outcomes, and the findings on autopsy. The disease was described as a disease of alcoholics and malnutrition. 'Central pontine' indicated the site of the lesion and 'myelinolysis' was used to emphasise that myelin was affected. The authors intentionally avoided the term 'demyelination' to describe the condition, in order to differentiate this condition from multiple sclerosis and other neuroinflammatory disorders.[2]

Since this original description, demyelination in other areas of the central nervous system associated with osmotic stress has been described outside the pons (extrapontine).[3] Osmotic demyelination syndrome is the term used for both central pontine myelinolysis and extrapontine myelinolysis.[4]

Central pontine myelinolysis, and osmotic demyelination syndrome, present most commonly as a complication of treatment of patients with profound hyponatremia (low sodium), which can result from a varied spectrum of conditions, based on different mechanisms. It occurs as a consequence of a rapid rise in serum tonicity following treatment in individuals with chronic, severe hyponatremia who have made intracellular adaptations to the prevailing hypotonicity.[5] [6]

Signs and symptoms

Symptoms depend on the regions of the brain involved. Prior to its onset, patients may present with the neurological signs and symptoms of hyponatraemic encephalopathy such as nausea and vomiting, confusion, headache and seizures. These symptoms may resolve with normalisation of the serum sodium concentration. Three to five days later, a second phase of neurological manifestations occurs correlating with the onset of myelinolysis. Observable immediate precursors may include seizures, disturbed consciousness, gait changes, and decrease or cessation of respiratory function.[7] [8]

The classical clinical presentation is the progressive development of spastic quadriparesis, pseudobulbar palsy, and emotional lability (pseudobulbar affect), with other more variable neurological features associated with brainstem damage. These result from a rapid myelinolysis of the corticobulbar and corticospinal tracts in the brainstem.[9]

In about ten per cent of people with central pontine myelinolysis, extrapontine myelinolysis is also found. In these cases symptoms of Parkinson's disease may be generated.

Causes

The most common cause is overly-rapid correction of low blood sodium levels (hyponatremia).[10] Apart from rapid correction of hyponatraemia, there are case reports of central pontine myelinolysis in association with hypokalaemia, anorexia nervosa when feeding is started, patients undergoing dialysis and burn victims. There is a case report of central pontine myelinolysis occurring in the context of refeeding syndrome, in the absence of hyponatremia.[2]

It has also been known to occur in patients suffering withdrawal symptoms of chronic alcoholism.[11] In these instances, occurrence may be entirely unrelated to hyponatremia or rapid correction of hyponatremia. It could affect patients who take some prescription medicines that are able to cross the blood-brain barrier and cause abnormal thirst reception - in this scenario the central pontine myelinolysis is caused by polydipsia leading to low blood sodium levels (hyponatremia).

In schizophrenic patients with psychogenic polydipsia, inadequate thirst reception leads to excessive water intake, severely diluting serum sodium.[12] With this excessive thirst combined with psychotic symptoms, brain damage such as central pontine myelinolysis[13] may result from hyperosmolarity caused by excess intake of fluids, (primary polydipsia) although this is difficult to determine because such patients are often institutionalised and have a long history of mental health conditions.[14]

It has been observed following hematopoietic stem cell transplantation.[15]

Central pontine myelinolysis may also occur in patients prone to hyponatremia affected by:

Pathophysiology

The currently accepted theory states that the brain cells adjust their osmolarities by changing levels of certain osmolytes like inositol, betaine, and glutamine in response to varying serum osmolality. In the context of chronic low plasma sodium (hyponatremia), the brain compensates by decreasing the levels of these osmolytes within the cells, so that they can remain relatively isotonic with their surroundings and not absorb too much fluid. The reverse is true in hypernatremia, in which the cells increase their intracellular osmolytes so as not to lose too much fluid to the extracellular space.[27]

With correction of the hyponatremia with intravenous fluids, the extracellular tonicity increases, followed by an increase in intracellular tonicity. When the correction is too rapid, not enough time is allowed for the brain's cells to adjust to the new tonicity, namely by increasing the intracellular osmoles mentioned earlier. If the serum sodium levels rise too rapidly, the increased extracellular tonicity will continue to drive water out of the brain's cells. This can lead to cellular dysfunction and central pontine myelinolysis.[28] [29]

Diagnosis

It can be diagnosed clinically in the appropriate context, but may be difficult to confirm radiologically using conventional imaging techniques. Changes are more prominent on MRI than on CT, but often take days or weeks after acute symptom onset to develop. Imaging by MRI typically demonstrates areas of hyperintensity on T2-weighted images.[30]

Treatment

To minimise the risk of this condition developing 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; or 18 mEq/L/48hrs; thus avoiding demyelination. No large clinical trials have been performed to examine the efficacy of therapeutic re-lowering of serum sodium, or other interventions sometimes advocated such as steroids or plasma exchange.Alcoholic patients should receive vitamin supplementation and a formal evaluation of their nutritional status.[31] [32]

Once osmotic demyelination has begun, there is no cure or specific treatment. Care is mainly supportive. Alcoholics are usually given vitamins to correct for other deficiencies. The favourable factors contributing to the good outcome in central pontine myelinolysis without hyponatremia were: concurrent treatment of all electrolyte disturbances, early intensive care unit involvement at the advent of respiratory complications, early introduction of feeding including thiamine supplements with close monitoring of the electrolyte changes and input.[2]

Research has led to improved outcomes.[33] Animal studies suggest that inositol reduces the severity of osmotic demyelination syndrome if given before attempting to correct chronic hyponatraemia.[34] Further study is required before using inositol in humans for this purpose.[35]

Prognosis

Though traditionally the prognosis is considered poor, a good functional recovery is possible. All patients at risk of developing refeeding syndrome should have their electrolytes closely monitored, including sodium, potassium, magnesium, glucose and phosphate.[2] Recent data indicate that the prognosis of critically ill patients may even be better than what is generally considered,[36] despite severe initial clinical manifestations and a tendency by the intensivists to underestimate a possible favorable evolution.[37] 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.[38] Permanent disabilities range from minor tremors and ataxia to signs of severe brain damage, such as spastic quadriparesis and locked-in syndrome.[39] Some improvements may be seen over the course of the first several months after the condition stabilizes.

The degree of recovery depends on the extent of the original axonal damage.[28]

External links

Notes and References

  1. Adams RD, Victor M, Mancall EL. Central pontine myelinolysis: a hitherto undescribed disease occurring in alcoholic and malnourished patients. . AMA Arch Neurol Psychiatry . 1959 . 81 . 2 . 154–72 . 10.1001/archneurpsyc.1959.02340140020004 . 13616772 .
  2. Bose P, Kunnacherry A, Maliakal P . Central pontine myelinolysis without hyponatraemia . The Journal of the Royal College of Physicians of Edinburgh . 41 . 3 . 211–214 . September 2011 . 21949915 . 10.4997/JRCPE.2011.305 . free .
  3. Gocht A, Colmant HJ . Central pontine and extrapontine myelinolysis: a report of 58 cases . Clinical Neuropathology . 6 . 6 . 262–270 . 1987 . 3322623 .
  4. Lampl C, Yazdi K . Central pontine myelinolysis . European Neurology . 47 . 1 . 3–10 . 2002 . 11803185 . 10.1159/000047939 . live . 46885398 . https://web.archive.org/web/20120306022240/http://content.karger.com/produktedb/produkte.asp?typ=fulltext&file=ene47003 . 2012-03-06 .
  5. Babar SM . SIADH associated with ciprofloxacin . The Annals of Pharmacotherapy . 47 . 10 . 1359–1363 . October 2013 . 24259701 . 10.1177/1060028013502457 . mdy-all . 36759747 .
  6. Yoon B, Shim YS, Chung SW . Central pontine and extrapontine myelinolysis after alcohol withdrawal . Alcohol and Alcoholism . 43 . 6 . 647–649 . 2008 . 18678596 . 10.1093/alcalc/agn050 . free .
  7. Musana AK, Yale SH . Central pontine myelinolysis: case series and review . WMJ . 104 . 6 . 56–60 . August 2005 . 16218318 .
  8. Odier C, Nguyen DK, Panisset M . Central pontine and extrapontine myelinolysis: from epileptic and other manifestations to cognitive prognosis . Journal of Neurology . 257 . 7 . 1176–1180 . July 2010 . 20148334 . 10.1007/s00415-010-5486-7 . 25301314 .
  9. Karp BI, Laureno R . Pontine and extrapontine myelinolysis: a neurologic disorder following rapid correction of hyponatremia . Medicine . 72 . 6 . 359–373 . November 1993 . 8231786 . 10.1097/00005792-199311000-00001 . 24829955 . free .
  10. Bernsen HJ, Prick MJ . Improvement of central pontine myelinolysis as demonstrated by repeated magnetic resonance imaging in a patient without evidence of hyponatremia . Acta Neurologica Belgica . 99 . 3 . 189–193 . September 1999 . 10544728 .
  11. Yoon B, Shim YS, Chung SW . Central pontine and extrapontine myelinolysis after alcohol withdrawal . Alcohol and Alcoholism . 43 . 6 . 647–649 . 2008 . 18678596 . 10.1093/alcalc/agn050 . free .
  12. Web site: Psychogenic Polydipsia (Excessive Fluid seeking Behaviour). https://web.archive.org/web/20150407070947/http://apadivisions.org/division-31/publications/articles/british-columbia/psychogenic-polydipsia.pdf . 2015-04-07 . live. Donald H . American Psychological Society Divisions.
  13. Lim L, Krystal A . Psychotic disorder in a patient with central and extrapontine myelinolysis . Psychiatry and Clinical Neurosciences . 61 . 3 . 320–322 . June 2007 . 17472602 . 10.1111/j.1440-1819.2007.01648.x . free .
  14. Gill M, McCauley M . Psychogenic polydipsia: the result, or cause of, deteriorating psychotic symptoms? A case report of the consequences of water intoxication . Case Reports in Psychiatry . 2015 . 846459 . 2015-01-21 . 25688318 . 4320790 . 10.1155/2015/846459 . free .
  15. Lim KH, Kim S, Lee YS, Kim KH, Kim J, Rhee J, Kim HJ, Yi HG, Oh SY, Lim JH, Han SW, Lee S, Kim I, Yoon SS, Park S, Kim BK . 6 . Central pontine myelinolysis in a patient with acute lymphoblastic leukemia after hematopoietic stem cell transplantation: a case report . Journal of Korean Medical Science . 23 . 2 . 324–327 . April 2008 . 18437020 . 2526450 . 10.3346/jkms.2008.23.2.324 . dead . https://web.archive.org/web/20090227043351/http://jkms.org/contents/jkms.php?pubyear=2008&vol=23&fpage=324 . 2009-02-27 .
  16. Singh N, Yu VL, Gayowski T . Central nervous system lesions in adult liver transplant recipients: clinical review with implications for management . Medicine . 73 . 2 . 110–118 . March 1994 . 8152365 . 10.1097/00005792-199403000-00004 . 37808180 . free .
  17. Kato T, Hattori H, Nagato M, Kiuchi T, Uemoto S, Nakahata T, Tanaka K . Subclinical central pontine myelinolysis following liver transplantation . Brain & Development . 24 . 3 . 179–182 . April 2002 . 11934516 . 10.1016/S0387-7604(02)00013-X . 22140717 .
  18. Martinez AJ, Estol C, Faris AA . Neurologic complications of liver transplantation . Neurologic Clinics . 6 . 2 . 327–348 . May 1988 . 3047544 . 10.1016/S0733-8619(18)30873-9 .
  19. McKee AC, Winkelman MD, Banker BQ . Central pontine myelinolysis in severely burned patients: relationship to serum hyperosmolality . Neurology . 38 . 8 . 1211–1217 . August 1988 . 3399069 . 10.1212/wnl.38.8.1211 . 42068902 .
  20. Winkelman MD, Galloway PG . Central nervous system complications of thermal burns. A postmortem study of 139 patients . Medicine . 71 . 5 . 271–283 . September 1992 . 1522803 . 10.1097/00005792-199209000-00002 . 12872586 . free .
  21. Sugimoto T, Murata T, Omori M, Wada Y . Central pontine myelinolysis associated with hypokalaemia in anorexia nervosa . Journal of Neurology, Neurosurgery, and Psychiatry . 74 . 3 . 353–355 . March 2003 . 12588925 . 1738317 . 10.1136/jnnp.74.3.353 .
  22. Keswani SC . Central pontine myelinolysis associated with hypokalaemia in anorexia nervosa . Journal of Neurology, Neurosurgery, and Psychiatry . 75 . 4 . 663; author reply 663 . April 2004 . 15026526 . 1739009 .
  23. Leroy S, Gout A, Husson B, de Tournemire R, Tardieu M . Centropontine myelinolysis related to refeeding syndrome in an adolescent suffering from anorexia nervosa . Neuropediatrics . 43 . 3 . 152–154 . June 2012 . 22473289 . 10.1055/s-0032-1307458 . 22751051 .
  24. Bergin PS, Harvey P . Wernicke's encephalopathy and central pontine myelinolysis associated with hyperemesis gravidarum . BMJ . 305 . 6852 . 517–518 . August 1992 . 1393001 . 1882865 . 10.1136/bmj.305.6852.517 .
  25. Sutamnartpong P, Muengtaweepongsa S, Kulkantrakorn K . Wernicke's encephalopathy and central pontine myelinolysis in hyperemesis gravidarum . Journal of Neurosciences in Rural Practice . 4 . 1 . 39–41 . January 2013 . 23546346 . 3579041 . 10.4103/0976-3147.105608 . free .
  26. Kishimoto Y, Ikeda K, Murata K, Kawabe K, Hirayama T, Iwasaki Y . Rapid development of central pontine myelinolysis after recovery from Wernicke encephalopathy: a non-alcoholic case without hyponatremia . Internal Medicine . 51 . 12 . 1599–1603 . 2012 . 22728498 . 10.2169/internalmedicine.51.7498 . free .
  27. Gankam Kengne . Fabrice . Decaux . Guy . 2017-09-01 . Hyponatremia and the Brain . Kidney International Reports . 3 . 1 . 24–35 . 10.1016/j.ekir.2017.08.015 . 2468-0249 . 5762960 . 29340311.
  28. Medana IM, Esiri MM . Axonal damage: a key predictor of outcome in human CNS diseases . Brain . 126 . Pt 3 . 515–530 . March 2003 . 12566274 . 10.1093/brain/awg061 . free .
  29. Spasovski G, Vanholder R, Allolio B, Annane D, Ball S, Bichet D, Decaux G, Fenske W, Hoorn EJ, Ichai C, Joannidis M, Soupart A, Zietse R, Haller M, van der Veer S, Van Biesen W, Nagler E . 6 . Clinical practice guideline on diagnosis and treatment of hyponatraemia . European Journal of Endocrinology . 170 . 3 . G1-47 . March 2014 . 24569125 . 10.1530/eje-13-1020 . free .
  30. Zimny A, Neska-Matuszewska M, Bladowska J, Sąsiadek MJ . Intracranial Lesions with Low Signal Intensity on T2-weighted MR Images - Review of Pathologies . Polish Journal of Radiology . 80 . 40–50 . 2015 . 25628772 . 4307690 . 10.12659/PJR.892146 .
  31. Kleinschmidt-DeMasters BK, Norenberg MD . Rapid correction of hyponatremia causes demyelination: relation to central pontine myelinolysis . Science . 211 . 4486 . 1068–1070 . March 1981 . 7466381 . 10.1126/science.7466381 . 1981Sci...211.1068K .
  32. Laureno R . Experimental pontine and extrapontine myelinolysis . Transactions of the American Neurological Association . 105 . 354–358 . 1980 . 7348981 .
  33. Brown WD . Osmotic demyelination disorders: central pontine and extrapontine myelinolysis . Current Opinion in Neurology . 13 . 6 . 691–697 . December 2000 . 11148672 . 10.1097/00019052-200012000-00014 . 36063964 .
  34. Silver SM, Schroeder BM, Sterns RH, Rojiani AM . Myoinositol administration improves survival and reduces myelinolysis after rapid correction of chronic hyponatremia in rats . Journal of Neuropathology and Experimental Neurology . 65 . 1 . 37–44 . January 2006 . 16410747 . 10.1097/01.jnen.0000195938.02292.39 . free .
  35. Web site: INOSITOL: Overview, Uses, Side Effects, Precautions, Interactions, Dosing and Reviews. 2021-10-14. www.webmd.com. en.
  36. Louis G, Megarbane B, Lavoué S, Lassalle V, Argaud L, Poussel JF, Georges H, Bollaert PE . 6 . Long-term outcome of patients hospitalized in intensive care units with central or extrapontine myelinolysis* . Critical Care Medicine . 40 . 3 . 970–972 . March 2012 . 22036854 . 10.1097/CCM.0b013e318236f152 . 205542487 .
  37. Young GB . Central pontine myelinolysis: a lesson in humility* . Critical Care Medicine . 40 . 3 . 1026–1027 . March 2012 . 22343870 . 10.1097/CCM.0b013e31823b8e0b .
  38. Abbott R, Silber E, Felber J, Ekpo E . Osmotic demyelination syndrome . BMJ . 331 . 7520 . 829–830 . October 2005 . 16210283 . 1246086 . 10.1136/bmj.331.7520.829 .
  39. Web site: Luzzio C . Central Pontine Myelinolysis. Medscape. 14 March 2017. 17 November 2015.

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