central pontine myelinolysis

File:Extrapontine myelinolysis T2 01.jpg (small, thin arrow), putamen (long arrow), with sparing of globus pallidus (broad arrow), suggestive of extrapontine myelinolysis (osmotic demyelination syndrome)]]

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.{{cite journal | vauthors = Musana AK, Yale SH | title = Central pontine myelinolysis: case series and review | journal = WMJ | volume = 104 | issue = 6 | pages = 56–60 | date = August 2005 | pmid = 16218318 }}{{cite journal | vauthors = Odier C, Nguyen DK, Panisset M | title = Central pontine and extrapontine myelinolysis: from epileptic and other manifestations to cognitive prognosis | journal = Journal of Neurology | volume = 257 | issue = 7 | pages = 1176–1180 | date = July 2010 | pmid = 20148334 | doi = 10.1007/s00415-010-5486-7 | s2cid = 25301314 }}

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.{{cite journal | vauthors = Karp BI, Laureno R | title = Pontine and extrapontine myelinolysis: a neurologic disorder following rapid correction of hyponatremia | journal = Medicine | volume = 72 | issue = 6 | pages = 359–373 | date = November 1993 | pmid = 8231786 | doi = 10.1097/00005792-199311000-00001 | s2cid = 24829955 | doi-access = free }}

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.

File:Pontine myelinolysis.jpg in the brainstem (Luxol-Fast blue stain)]]

The most common cause is overly-rapid correction of low blood sodium levels (hyponatremia).{{cite journal | vauthors = Bernsen HJ, Prick MJ | title = Improvement of central pontine myelinolysis as demonstrated by repeated magnetic resonance imaging in a patient without evidence of hyponatremia | journal = Acta Neurologica Belgica | volume = 99 | issue = 3 | pages = 189–193 | date = September 1999 | pmid = 10544728 }} 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.

It has also been known to occur in patients suffering withdrawal symptoms of chronic alcoholism.{{cite journal | vauthors = Yoon B, Shim YS, Chung SW | title = Central pontine and extrapontine myelinolysis after alcohol withdrawal | journal = Alcohol and Alcoholism | volume = 43 | issue = 6 | pages = 647–649 | year = 2008 | pmid = 18678596 | doi = 10.1093/alcalc/agn050 | doi-access = free }} 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).{{cn|date=December 2020}}

In schizophrenic patients with psychogenic polydipsia, inadequate thirst reception leads to excessive water intake, severely diluting serum sodium.{{Cite web|url=http://www.apadivisions.org/division-31/publications/articles/british-columbia/psychogenic-polydipsia.pdf |archive-url=https://web.archive.org/web/20150407070947/http://apadivisions.org/division-31/publications/articles/british-columbia/psychogenic-polydipsia.pdf |archive-date=2015-04-07 |url-status=live|title=Psychogenic Polydipsia (Excessive Fluid seeking Behaviour)| vauthors = Donald H |publisher=American Psychological Society Divisions}} With this excessive thirst combined with psychotic symptoms, brain damage such as central pontine myelinolysis{{cite journal | vauthors = Lim L, Krystal A | title = Psychotic disorder in a patient with central and extrapontine myelinolysis | journal = Psychiatry and Clinical Neurosciences | volume = 61 | issue = 3 | pages = 320–322 | date = June 2007 | pmid = 17472602 | doi = 10.1111/j.1440-1819.2007.01648.x | doi-access = free }} 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.{{cite journal | vauthors = Gill M, McCauley M | title = Psychogenic polydipsia: the result, or cause of, deteriorating psychotic symptoms? A case report of the consequences of water intoxication | journal = Case Reports in Psychiatry | volume = 2015 | pages = 846459 | date = 2015-01-21 | pmid = 25688318 | pmc = 4320790 | doi = 10.1155/2015/846459 | doi-access = free }}

It has been observed following hematopoietic stem cell transplantation.{{cite journal | vauthors = 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 | display-authors = 6 | title = Central pontine myelinolysis in a patient with acute lymphoblastic leukemia after hematopoietic stem cell transplantation: a case report | journal = Journal of Korean Medical Science | volume = 23 | issue = 2 | pages = 324–327 | date = April 2008 | pmid = 18437020 | pmc = 2526450 | doi = 10.3346/jkms.2008.23.2.324 | url = http://jkms.org/contents/jkms.php?pubyear=2008&vol=23&fpage=324 | url-status = dead | archive-url = https://web.archive.org/web/20090227043351/http://jkms.org/contents/jkms.php?pubyear=2008&vol=23&fpage=324 | archive-date = 2009-02-27 }}

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

• Severe liver disease (e.g., cirrhosis)
• Liver transplant{{cite journal | vauthors = Singh N, Yu VL, Gayowski T | title = Central nervous system lesions in adult liver transplant recipients: clinical review with implications for management | journal = Medicine | volume = 73 | issue = 2 | pages = 110–118 | date = March 1994 | pmid = 8152365 | doi = 10.1097/00005792-199403000-00004 | s2cid = 37808180 | doi-access = free }}{{cite journal | vauthors = Kato T, Hattori H, Nagato M, Kiuchi T, Uemoto S, Nakahata T, Tanaka K | title = Subclinical central pontine myelinolysis following liver transplantation | journal = Brain & Development | volume = 24 | issue = 3 | pages = 179–182 | date = April 2002 | pmid = 11934516 | doi = 10.1016/S0387-7604(02)00013-X | s2cid = 22140717 }}{{cite journal | vauthors = Martinez AJ, Estol C, Faris AA | title = Neurologic complications of liver transplantation | journal = Neurologic Clinics | volume = 6 | issue = 2 | pages = 327–348 | date = May 1988 | pmid = 3047544 | doi = 10.1016/S0733-8619(18)30873-9 }}
• Alcoholism
• Hypokalemia
• People with serum sodium <105 mEq/L
• Severe burns{{cite journal | vauthors = McKee AC, Winkelman MD, Banker BQ | title = Central pontine myelinolysis in severely burned patients: relationship to serum hyperosmolality | journal = Neurology | volume = 38 | issue = 8 | pages = 1211–1217 | date = August 1988 | pmid = 3399069 | doi = 10.1212/wnl.38.8.1211 | s2cid = 42068902 }}{{cite journal | vauthors = Winkelman MD, Galloway PG | title = Central nervous system complications of thermal burns. A postmortem study of 139 patients | journal = Medicine | volume = 71 | issue = 5 | pages = 271–283 | date = September 1992 | pmid = 1522803 | doi = 10.1097/00005792-199209000-00002 | s2cid = 12872586 | doi-access = free }}
• Malnutrition
• Anorexia nervosa{{cite journal | vauthors = Sugimoto T, Murata T, Omori M, Wada Y | title = Central pontine myelinolysis associated with hypokalaemia in anorexia nervosa | journal = Journal of Neurology, Neurosurgery, and Psychiatry | volume = 74 | issue = 3 | pages = 353–355 | date = March 2003 | pmid = 12588925 | pmc = 1738317 | doi = 10.1136/jnnp.74.3.353 }}{{cite journal | vauthors = Keswani SC | title = Central pontine myelinolysis associated with hypokalaemia in anorexia nervosa | journal = Journal of Neurology, Neurosurgery, and Psychiatry | volume = 75 | issue = 4 | pages = 663; author reply 663 | date = April 2004 | pmid = 15026526 | pmc = 1739009 }}{{cite journal | vauthors = Leroy S, Gout A, Husson B, de Tournemire R, Tardieu M | title = Centropontine myelinolysis related to refeeding syndrome in an adolescent suffering from anorexia nervosa | journal = Neuropediatrics | volume = 43 | issue = 3 | pages = 152–154 | date = June 2012 | pmid = 22473289 | doi = 10.1055/s-0032-1307458 | s2cid = 22751051 }}
• Severe electrolyte disorders
• HIV/AIDS
• hyperemesis gravidarum{{cite journal | vauthors = Bergin PS, Harvey P | title = Wernicke's encephalopathy and central pontine myelinolysis associated with hyperemesis gravidarum | journal = BMJ | volume = 305 | issue = 6852 | pages = 517–518 | date = August 1992 | pmid = 1393001 | pmc = 1882865 | doi = 10.1136/bmj.305.6852.517 }}{{cite journal | vauthors = Sutamnartpong P, Muengtaweepongsa S, Kulkantrakorn K | title = Wernicke's encephalopathy and central pontine myelinolysis in hyperemesis gravidarum | journal = Journal of Neurosciences in Rural Practice | volume = 4 | issue = 1 | pages = 39–41 | date = January 2013 | pmid = 23546346 | pmc = 3579041 | doi = 10.4103/0976-3147.105608 | doi-access = free }}
• Hyponatremia due to peritoneal dialysis
• Wernicke encephalopathy{{cite journal | vauthors = Kishimoto Y, Ikeda K, Murata K, Kawabe K, Hirayama T, Iwasaki Y | title = Rapid development of central pontine myelinolysis after recovery from Wernicke encephalopathy: a non-alcoholic case without hyponatremia | journal = Internal Medicine | volume = 51 | issue = 12 | pages = 1599–1603 | year = 2012 | pmid = 22728498 | doi = 10.2169/internalmedicine.51.7498 | doi-access = free }}

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.{{Cite journal |last1=Gankam Kengne |first1=Fabrice |last2=Decaux |first2=Guy |date=2017-09-01 |title=Hyponatremia and the Brain |journal=Kidney International Reports |volume=3 |issue=1 |pages=24–35 |doi=10.1016/j.ekir.2017.08.015 |issn=2468-0249 |pmc=5762960 |pmid=29340311}}

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.{{cite journal | vauthors = Medana IM, Esiri MM | title = Axonal damage: a key predictor of outcome in human CNS diseases | journal = Brain | volume = 126 | issue = Pt 3 | pages = 515–530 | date = March 2003 | pmid = 12566274 | doi = 10.1093/brain/awg061 | doi-access = free }}{{cite journal | vauthors = 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 | display-authors = 6 | title = Clinical practice guideline on diagnosis and treatment of hyponatraemia | journal = European Journal of Endocrinology | volume = 170 | issue = 3 | pages = G1-47 | date = March 2014 | pmid = 24569125 | doi = 10.1530/eje-13-1020 | doi-access = free }}

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.{{cite journal | vauthors = Zimny A, Neska-Matuszewska M, Bladowska J, Sąsiadek MJ | title = Intracranial Lesions with Low Signal Intensity on T2-weighted MR Images - Review of Pathologies | journal = Polish Journal of Radiology | volume = 80 | pages = 40–50 | date = 2015 | pmid = 25628772 | pmc = 4307690 | doi = 10.12659/PJR.892146 }}

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.{{cite journal | vauthors = Kleinschmidt-DeMasters BK, Norenberg MD | title = Rapid correction of hyponatremia causes demyelination: relation to central pontine myelinolysis | journal = Science | volume = 211 | issue = 4486 | pages = 1068–1070 | date = March 1981 | pmid = 7466381 | doi = 10.1126/science.7466381 | bibcode = 1981Sci...211.1068K }}{{cite journal | vauthors = Laureno R | title = Experimental pontine and extrapontine myelinolysis | journal = Transactions of the American Neurological Association | volume = 105 | pages = 354–358 | year = 1980 | pmid = 7348981 }}

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.

Research has led to improved outcomes.{{cite journal | vauthors = Brown WD | title = Osmotic demyelination disorders: central pontine and extrapontine myelinolysis | journal = Current Opinion in Neurology | volume = 13 | issue = 6 | pages = 691–697 | date = December 2000 | pmid = 11148672 | doi = 10.1097/00019052-200012000-00014 | s2cid = 36063964 }} Animal studies suggest that inositol reduces the severity of osmotic demyelination syndrome if given before attempting to correct chronic hyponatraemia.{{cite journal | vauthors = Silver SM, Schroeder BM, Sterns RH, Rojiani AM | title = Myoinositol administration improves survival and reduces myelinolysis after rapid correction of chronic hyponatremia in rats | journal = Journal of Neuropathology and Experimental Neurology | volume = 65 | issue = 1 | pages = 37–44 | date = January 2006 | pmid = 16410747 | doi = 10.1097/01.jnen.0000195938.02292.39 | doi-access = free }} Further study is required before using inositol in humans for this purpose.{{Cite web|title=INOSITOL: Overview, Uses, Side Effects, Precautions, Interactions, Dosing and Reviews|url=https://www.webmd.com/vitamins/ai/ingredientmono-299/inositol|access-date=2021-10-14|website=www.webmd.com|language=en}}

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.

Recent data indicate that the prognosis of critically ill patients may even be better than what is generally considered,{{cite journal | vauthors = Louis G, Megarbane B, Lavoué S, Lassalle V, Argaud L, Poussel JF, Georges H, Bollaert PE | display-authors = 6 | title = Long-term outcome of patients hospitalized in intensive care units with central or extrapontine myelinolysis* | journal = Critical Care Medicine | volume = 40 | issue = 3 | pages = 970–972 | date = March 2012 | pmid = 22036854 | doi = 10.1097/CCM.0b013e318236f152 | s2cid = 205542487 }} despite severe initial clinical manifestations and a tendency by the intensivists to underestimate a possible favorable evolution.{{cite journal | vauthors = Young GB | title = Central pontine myelinolysis: a lesson in humility* | journal = Critical Care Medicine | volume = 40 | issue = 3 | pages = 1026–1027 | date = March 2012 | pmid = 22343870 | doi = 10.1097/CCM.0b013e31823b8e0b }}

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.{{cite journal | vauthors = Abbott R, Silber E, Felber J, Ekpo E | title = Osmotic demyelination syndrome | journal = BMJ | volume = 331 | issue = 7520 | pages = 829–830 | date = October 2005 | pmid = 16210283 | pmc = 1246086 | doi = 10.1136/bmj.331.7520.829 }} Permanent disabilities range from minor tremors and ataxia to signs of severe brain damage, such as spastic quadriparesis and locked-in syndrome.{{cite web| vauthors = Luzzio C |title=Central Pontine Myelinolysis|url=http://emedicine.medscape.com/article/1174329-overview|website=Medscape|access-date=14 March 2017|date=17 November 2015}} Some improvements may be seen over the course of the first several months after the condition stabilizes.{{citation needed|date=July 2021}}

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

{{Reflist}}

• [https://web.archive.org/web/20130219024253/http://rad.usuhs.mil/medpix/medpix.html?mode=image_finder&srchstr=osmotic+myelinolysis&search=#top MedPix] Images of Osmotic Myelinolysis

{{Medical resources

| ICD11 = {{ICD11|8A45.31}}

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{{Demyelinating diseases of CNS}}

Category:Demyelinating diseases of CNS

Category:Electrolyte disturbances