id correction of serum sodium. In di- abetic ketoacidosis, the marked. Keywords Myelinolysis ·. Ketoacidosis · Hyponatraemia · MRI. Fax: +52-555-6656238.
Eur Radio! (2004) 14:549- 551 DOl lO.l007/s00330-003-1941-5
INTERPRETATION CORNER
© Springer-Verlag 2003
E. Roldan-Valadez S. Osorio-Peralta P. Hernandez-Martinez C. Sandoval-Gonzalez G. Casian-Castellanos
E. Roldan-Valadez· S. Osorio-Peralta P. Hernandez-Martinez C. Sandoval-Gonzalez G. Casian-Castellanos Department of Radiology, Medica Sur Clinic & Foundation, Mexico City, Mexico E. Roldan-Valadez (~) Medica Sur Clinic & Foundation, Departamento de Enseiianza. 4°, Pi so, Torre I, Puente de Piedra, 150, Col. Toriello Guerra. Deleg. Tlalpan, CP 14050 Mexico City, Mexico E-mail: ernest.roldan@ usa. net Tel. : +52-555-4247200 Fax: +52-555-6656238
Early MRI findings of central pontine myelinolysis following "rapid" correction of hyponatraemia during diabetic ketoacidosis. A curious pontine lesion (2003: 12b}
S. Osorio-Peralta · P. Hernandez-Martinez, C. Sandoval-Gonzalez G. Casian-Castellanos Department of Radiology, Hospital Juarez de Mexico, Secretariat of Health, Mexico City, Mexico
Abstract We describe a diabetic patient with hyponatraemia and ketoacidosis who developed centra] pontine myelinolysis (CPM) after a very rapid correction of serum sodium. In diabetic ketoacidosis, the marked shifts in osmolarity make these pa-
Introduction First described by Adams et al. [1], central pontine myelinolysis (CPM) is a disorder of demyelination caused by rapid normalization of serum sodium in patients with chronic hyponatraemia [2, 3, 4]. Rapid correction can cause osmotic endothelial injury secondary to rising sodium levels that lead to the release of myelinotoxic factors which predominantly act on the more vascular grey matter [5]. Apoptosis has also been found as a mechanism of oligodendrocytic death in CPM [6]. It is characterized by demyelination which affects the central portion of the base of the pons. There are no inflammatory changes and blood vessels are normal [7].
Case report A 58-year-old woman diagnosed as diabetic at the age of 50 years had been repeatedly hospitalized in the previous 5 years because of poor control of her diabetes. On day 1 of this report, she was admitted as an emergency because of diabetes complicated with an event of ketoacidosis and a urinary tract infection. On adrnis-
tients more susceptible to the development of CPM. The dramatic early MRI findings (after 3 weeks) should raise awareness of the risk of permanent damage to the brain associated with hydration therapy in this susceptible group. Magnetic resonance imaging might be a useful investigation at presentation and follow-up of diabetic patients with extreme metabolic derangements. Keywords Myelinolysis · Ketoacidosis · Hyponatraemia · MRI
sion, her serum sodium level was 97 mEq/1 (reference ranges shown parenthetically; 136-145 mEq/1). The hyponatraernia was treated, and within 24 h it was corrected to 130 mEq/1 and after 48 h to 135 mEq/1. Results of other laboratory studies at that time were as follows: white blood cell count, 18xJ09JJ (4-12x109f1); serum urea nitrogen, 192 mg/dl (7- 21 mg/dl); serum creatinine, 5.2 mg/dl (0.9-l.l mg/dl); serum potassium, 2.1 mEq/1 (3.65.2 mEq/1); serum chloride, 88 mEqll (100-108 mEq/1); bicarbonate, 18 mEq/1 (21- 32 mEq/1); glucose, 316 mEq/1 (90-120 mg/dl); and vitamin B 12, 422 pg/ml (157- 1059 pg/ml). Findings on cerebrospinal fluid examination were normal. Chest radiography was normal. Urine cultures grew E. coli. Blood cultures were negative. She received intravenous administration of antibiotics and electrolytes. After 4 days the patient was transferred to the outpatient clinic for control and follow-up. She presented 3 weeks later with a history of nausea, decreased appetite and inability to walk for over a week. On physical examination, she was noted to be very somnolent with a blunted affect. She had dysarthria and loss of memory. She was clumsy while performing finger-nose and heel-knee manoeuvres on both sides. Sensation had decreased (proprioception and vibration). Deep tendon jerks were 3+ and symmetric, and the Babinski sign was negative bilaterally. The patient was markedly ataxic while walking with a wide-based gait. She was afebrile, all other vital signs were unremarkable and laboratory studies were within normal ranges except for blood glucose, 192 mEq/1. In view of her neurological signs M RI was performed. This revealed an area of increased signal intensity within the central pons on T2-weighted images (de-
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Usually, CPM occurs when correction of the serum sodium level exceeds 12 mEq/1 a day [7, II]. It is believed that during hyponatraemia, adaptive changes in the central nervous system prevent the development of cerebral oedema; these include a gradual loss of intracellular organic osmolytes, including phosphocreatine, myoinositol and glutamate, which fall significantly in the first 24 h of hyponatraemia, lowering the osmotic gradient between blood and brain [9, I0). Once depleted, these osmolytes only reaccumulate slowly, requiring >5 days to reach normal levels during correction of hyponatraemia and placing the brain at risk of osmotic dehydration if serum osmolarity is corrected rapidly [12J. How this leads to selective loss of myelin is uncertain, but several possible mechanisms have been postulated, including physical shearing of myelin from axons due to cell shrinkage, effects of localized perivascular oedema after disruption of the blood-brain barrier, and increased oxidation of myelin components [8, 13]. Potassium depletion as part of ketoacidosis may also be relevant and appears to be an important cofactor in the development of myelinolysis present in the majority of reported cases [ 14]. One study suggested that the increase in serum sodium produces an osmotic endothelial injury that leads to local release of myelinotoxic factors derived from the Fig. J a A T2-weighted magnetic resonance image. Axial view more vascular grey matter [5]. The fact that myelinolysis shows an area of hyperintcnsity in the central pons. b A T !- does not occur in pure white matter tracts, such as the inweighted magnetic resonance image. Sagittal view shows an area of bypointensity in the central pons, and there is an incidental ternal capsule, supports this hypothesis. In these situafmding of a small arachnoid cyst. c A Tl-weighted magnetic reso- tions, the brain may be incapable of generating new osnance image. Axial view shows an area of hypointensity in the moles in response to a rapid increase in serum osmolalipons. d An axial Tl-wcighted magnetic resonance image en- ty, resulting in excessive endothelial shrinkage and injuhanced with intravenous gadolinium-DTPA shows enhancement of ry [7]. the cavernous sinuses, hypophysis and infundibulum. The enThe characteristic clinkal manifestations of myelinolhanced venous vessels correspond to the confluence of sinuses (Herophilus' lacuum). The area of hypointensity in the pons, the ysis are spastic tetraparesis and pseudobulbar paralysis. same as shown in c, did not enhance with the intravenous gadolin- Pseudobulbar paralysis leads to dysphagia, dysarthria, ium-DTPA weakness of the tongue and emotional lability. Destructive lesions in the corticospinal and the corticobulbar tracts in the pons cause these findings. A large central creased signal intensity on Tl images; Fig. Ia, b, c). The lesion ar- pontine lesion can cause a locked-in syndrome [151. ea on Tl-weighted images did not enhance with intravenous gado- Variations include weakness that is worse in the arms linium-DTPA (Fig. ld). During the following week, the patient's dysarthria improved, and her mental status was norrnal, but she compared with the legs and weakness in a hemiplegic still experienced ataxia at the time of discharge I week later. She distribution [16]. Lesions involving the descending ocdid not return to the outpatient clinic for follow-up. ulosympathetic tracts can cause bilateral miosis, whereas lesions that involve the lower pons can cause unilateral or bilateral sixth nerve palsy. The patient's level of conDiscussion sciou..c;ness may be impaired, varying from lethargy to coma. Such changes in consciousness are usually due to The patient was a woman with a 9-year history of diabe- the lesion extending from the base of the pons into the tes characterized by chronic poor control and multiple tegmentum of pons. complications. Although CPM was first described in This report showed the development of CPM in a dia1959 in a clinicopathological study of four fatal cases betic patient with ketoacidosis after an accelerated elecoccurring in alcoholic or malnourished patients [I], there trolyte rectification. She had an initial serum sodium levhave been numerous further reports in the literature, and el of 97 mEq/1 and was hydrated rapidly, far faster than il is now apparent that the clinical presentation of CPM the cunent recommendations which limit the increase in is very varied [8J. Only very few of the previous reports serum sodium concentration to 12 mEq/1 in the first 24 h have included patients with diabetes [9, 10]. and to 20 mEqllL in the initial 48 h [ 17, 18].
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The literature shows that patients with CPM usually have an underlying medical disease, especially alcoholism and liver disease. ln diabetic ketoacidosis, the marked shifts in osmolarity and metabolic derangements that occur (deficit of insulin, hyperglycaemia, depletion of volume and electrolytes, acidosis) make these patients more susceptible to the development of CPM. The fact that myelinolysis has not been observed more often has raised the question of whether any adaptive changes occur in brain metabolism that may intrinsically protect diabetic patients from the effects of osmotic stress [ 19]. There is no information from MRI about the minimum
time before signs of CPM may be encountered. Magnetic resonance imaging does not always detect lesions within the first 2 weeks after correction of hyponatraemia; it has even failed to show lesions that were found at autopsy [20]. Although we considered this case an extreme situation, the early MRl findings of CPM in this patient could help to highlight the risk of early permanent damage to the brain with non-cautious hydration therapies in these more susceptible patients. Magnetic resonance imaging might be justified in the initial evaluation and fol1ow-up of diabetic patients with major metabolic disorders.
References 1. Adams RD, Victor M, Mancall EL (J 959) Central Pontine Mielinolysis: a hitherto undescribed disease occurring in alcoholic and malnourished patients. AMA Arch Neurol Psychiatry 81 :154-172 2. Stems RR, Ri ggs IE, Schochet SS (1986) Osmotic demyelination syndrome following correction of hyponatremia. N Eng! J Med 3 14:1535- 1542 3. Lau reno R ( 1983) Central pontine myelinolysis following rapid correction of hyponatremia Ann Neurol 13:232- 242 4. Norenberg MD, Leslie KO, Robertson AS ( 1982) Association between rise in serum sodium and central pontine myelinolysis. Ann Neurol 11 :128-135 5. Norenberg MD (1983) A hypothesis of osmotic endothelial injury. A pathogenetic mechanism in central pontine myelinolysis. Arch Neurol 40:66-69 6. DeLuca GC, Nagy Z. Esiri MM. Davey P (2002) Evidence for a role for apoptosis in central pontine myelinolysis. Acta Neuropathol (Berl) I 03:590-598 7. Pirzada NA, Ali II (2001) Central pontine myelinolysis. Mayo Clin Proc 76:559-562
8. Laureno R, Karp BI ( 1997) Myelinolysis after correction of hyponatremia. Ann Intern Med 126:57-62 9. Cliford DB, Gado MH, Levy BK ( 1989) Osmotic demyelination syndrome: lack of pathologic and radiologic imaging correlation. Arch Neurol 46:343- 347 10. Rajbhandari SM, Powell T, DaviesJones GA, Ward JD (1998) Central pontine myelinolysis and ataxia: an unusual manifestation of hypoglycaemia. Diabet Med 15:259-261 11. Ayus JC, Krothapali RK, Arieff AJ (1987) Treatment of hyponatremia and its relation to brain damage. N Eng I J Med 3 17:1190-1195 12. Verbalis JG , Gullans SR ( 1993) Rapid correction of hyponatremia produces differential effects on brain osmolytc and electrolyte re-aecumulation in rats. Brain Res 606:19-27 13. Stems RR, Thomas DJ, Herndon RM (1989) Brain dehydration and neurological deterioration after correction of hyponatremia: Kidney Int 25:69-75 14. Lohr JW (1994) Osmo6c demyelination syndrome following correction of hyponatremia: association with hypokalemia. Am J Med 96:408-413
I 5. Messert B, Orrison WW, Hawkins MJ,
Quaglieri CE (1979) Central pontine myelinolysis. Considerations on etiology, diagnosis, and treatmenL Neurology 29:147-160 16. Marra TR ( 1983) Hemiparesis apparently due to central pontine myelinol ysis following hyponatremia Ann Neuroll4:687-688 17. Sterns RH ( 1987) Severe symptomatic hyponatremia: treatment and outcome: a study of 64 ca.~es. Ann Intern Med 107:656-664 18. Adams RD, Victor M ( I 993) Principles of neurology. McGraw-Hill, New York, pp 891 - 893 19. Casey E, Evans A, Krentz A, Watkins P, Hopkins D (1999) Central pontine myelinolysis. An unusual complication of diabetes. Diabetes Care 22:998- 1000 20. Karp Bl, Laureno R (1993) Pontine and extrapontine myelinolysis: a neurologic disorder following rapid correction of hyponatremia. Medicine (Baltimore) 72:359-373
Precisely correct answers were received by the closing date f rom:
Rakesh Aggarwal, Canada Canan Altay, Yzmyr, Turkey Maria Argyropolou, Ioannina, Greece Haris Chrysikopoulos, Corfu, Greece Philippe Demaerel, Leuven, Belgium Cristine Galvao, Barretos, Brasil Sam Heye, Leuven, Belgium Theo Hose, Woerden, The Netherlands Marc Keberle, Wuerzburg, Germany Ercan Kocakoc, Elazig, Turkey NBS Mani, Nassau, Bahamas
PB Mattelaer, Brugge, Belgium Manabu Minami, Tokyo, Japan Sankar Monda!, Nassau, Bahamas Narendrakumar Patel, New York, USA Tauqir Rana, Riyadh, Saudi Arabia Mustafa Secil , Izmir, Turkey Filip Vanhoenacker, Mechelen-Duffel, Belgium
