J Neurol (1990) 237 : 275-276
Journal of
Neurology © Springer-Verlag 1990
Central pontine myelinolysis associated with iow potassium levels in alcoholism M. Bähr 1, N. Sommer 1, D. Petersen:, H. Wiethölter 1, and J. Dichgans ~ Departments of 1Neurology and 2Neuroradiology, University of Tübingen, Tübingen, Federal Republic of Germany Received February 16, 1990 / Accepted March 1, 1990
Summary. Two patients with chronic alcohol abuse and central pontine myelinolysis are described. One developed a Korsakoff syndrome 2 days before admission to our hospital and the other showed signs of a incipient delirium without Korsakoff syndrome. Diagnosis of incipient central pontine myelinolysis was based on acute brain-stem dysfunction, serum electrolyte disturbances, malnutrition with vitamin B1 (thiamine), B6 (pyridoxine) and B12 (cyanocobalamine) deficiency in combination with typical neuroradiological findings. H y p o k a l a e m i a but no disturbance in serum sodium levels was found in both patients. After correction of h y p o k a l a e m i a and vitamin deficiency the patients showed complete recovery of neurological and neuropsychological function. The findings are interpreted as suggesting that disturbances in serum potassium levels as well as rapid correction of h y p o n a t r a e m i a may be associated with pontine swelling and dysfunction which, if undetected, leads to central pontine myelinolysis.
Key words: Central pontine myelinolysis - Serum electrolytes - Magnetic resonance imaging - Vitamin
Introduction Since central pontine myelinolysis (CPM) was first described as a clinical entity [1] it has b e e n considered that rapid changes in serum electrolyte levels might be pathogenetically involved in its development [6, 8-10]. Experimental and clinical data [7] have suggested that CPM might be related to rapid correction of a preceding hyponatraemia, hut n o r m o n a t r a e m i c and hypernatraemic patients have also been described [3, 5, 6] and the exact mechanism leading to the acute brain-stem dysfunction is still unknown. CPM predominantly occurs in patients with chronic alcohol abuse [3, 4, 8], liver disease [3, 6] and malnutrition [1, 3]. Clinically acute brain-stem dysfunction together with serum electrolyte disturbances Offprint requests to: M. Bähr, Neurologische Universitätsklinik, Hoppe-Seylerstrasse 3, D-7400 Tübingen, Federal Republic of Germany
and typical neuroradiological findings [2, 5, 11, 13, 14] can lead to the intra vitam diagnosis of a CPM, Early detection and t r e a t m e n t of a CPM [10, 12], which often follows delirium tremens, seem to be critical for the clinical outcome of patients. The purpose of the present p a p e r is to point out that not only disturbances of serum sodium but also those of serum potassium in combination with malnutrition and subsequent vitamin-B deficiency due to chronic alcohol abuse may be associated with brain-stem lesions that can be detected by c o m p u t e d t o m o g r a p h y (CT) and magnetic resonance imaging (MRI). M o r e o v e r , the cases presented seem to indicate that the early and rapid correction of hypokalaemia (unlike the slow correction of low serum sodium levels) and malnutrition m a y substantially improve the clinical outcome of patients with incipient CPM.
Case reports Case 1 A 59-year-old right-handed male patient was admitted to our hospital because of an acute Korsakoff syndrome with eonfabulation, memory impairment and disorientation. Within hours coma developed. Neurological examination showed an impaired optokinetic nystagmus and bilateral latent signs of a brain-stem dysfunetion. Serum electrolyte analysis revealed severe hypokalaemia of less than 3 mmol/1 and low levels of vitamins B1, B6, and BI2. Serum sodium levels were always normal (137-139mmol/1). Initial CT showed brain-stem swelling and a generalized hypodensity which extended from the pons to paraventricular areas. MRI 3 days after admission showed an irregular pattern of hyperintensities of the white matter, not particularly in the pontine region, compatible with chronic subcortical vascular lesions. On follow-up MRI 2 weeks later the subcortieal lesions were unchanged, hut within the pons a large, triangular-shaped hyperintensity on T2-weighted images was seen (Fig. 1). Initially the patient, as examined by transcranial Doppler sonography, had a reduced blood flow of the vertebral and basilar arteries, probably due to the swelling of the brain-stem. Correction of serum potassium levels and malnutrition by infusion therapy led to quick recovery of consciousness. At the time of discharge from the hospital the patient had no remaining neurological or neuropsychological deficits.
276
Fig.1. Corresponding T2-weighted axial MR images (SE 2.0/90) at 3 days (a) and at 20 days after admission to the hospital (b). a A completely normal brain-stem was found, b MRI 17 days later showed a central pontine hyperintense lesion
Case 2 A 32-year-old right-handed female alcoholic was admitted to the hospital with impaired consciousness after abrupt alcohol abstinence of her own choice. The patient developed a severe hypokalaemia of 2.6 mmol/1 serum potassium with normal serum sodium levels (133mmol/l) but no evidence of malnutrition. Electrolyte disturbance was corrected within 36 h but the neurological symptoms deteriorated with impaired consciousness, dysarthria, difficulty in swallowing, areflexia and sensory ataxia. She was therelore transferred to an intensive care unit, where she developed myoclonic jerks in all limbs and in facial muscles. The diagnosis of CPM was made clinically. CT and MRI did not show any pontine lesions. During the phase of clinical recovery (about 2 weeks after admission) MRI showed a well-defined lesion of 6-8 mm in diameter in the central pons with a bright signal on T2-weighted axial images and no brain-stem swelling. At the time of discharge the patient only showed slight ataxia and no brain-stem dysfunction.
Discussion W e h a v e d e s c r i b e d 2 p a t i e n t s with a l c o h o l a b u s e who dev e l o p e d a c u t e b r a i n - s t e m d y s f u n c t i o n a s s o c i a t e d with sev e r e s e r u m p o t a s s i u m d i s t u r b a n c e . C T a n d M R I conf i r m e d a lesion o f the p o n s at l a t e r stages. Clinical a n d neurological data (impaired consciousness, impaired opt o k i n e t i c s a n d t e t r a p a r e s i s in c o m b i n a t i o n with s e r u m e l e c t r o l y t e d i s t u r b a n c e s ) l e d to the d i a g n o s i s of i n c i p i e n t CPM. T h e o n s e t o f s y m p t o m s in the two p a t i e n t s with alc o h o l i s m c o r r e l a t e d weil with h y p o k a l a e m i a a n d m a l n u trition. T h e s e findings suggest a p o s s i b l e i n v o l v e m e n t of s e r u m p o t a s s i u m d i s t u r b a n c e s w i t h o u t h y p o n a t r a e m i a in t h e p a t h o g e n e s i s of C P M . M o s t p r e v i o u s r e p o r t s have f o c u s e d o n the a s s o c i a t i o n b e t w e e n h y p o n a t r a e m i a a n d C P M [3, 7, 8, 11]. In p a r t i c u l a r , t h e r a p i d rise of s e r u m s o d i u m levels o r o v e r c o r r e c t i o n o f h y p o n a t r a e m i a which m a y l e a d to h y p e r o s m o l a l i t y h a v e b e e n d e s c r i b e d to be p a t h o g e n e t i c a l l y i n v o l v e d in C P M [7, 8, 11]. T h e r e h a v e b e e n s e v e r a l r e p o r t s , h o w e v e r , o f C P M in n o r m o n a t r a e m i c o r p r i m ä r i l y h y p e r n a t r a e m i c p a t i e n t s . B o t h norm o n a t r a e m i c a n d h y p o n a t r a e m i c p a t i e n t s with h y p o k a l a e m i a h a v e also b e e n d e s c r i b e d [3, 6]. W h e t h e r the p o n -
tine dysfunction and s u b s e q u e n t m y e l i n o l y t i c lesions are r e l a t e d to shifts in s e r u m o s m o l a l i t y o r m o r e specifically l i n k e d to c h a n g e s in i n t r a c e l l u l a r s o d i u m o r p o t a s s i u m levels t h e r e f o r e r e m a i n s to b e e l u c i d a t e d . T h e o b s e r v a t i o n , h o w e v e r , that a h e t e r o g e n e i t y of s e r u m e l e c t r o l y t e d i s t u r b a n c e s is a s s o c i a t e d with C P M indicates that not only the toxic effects of a l c o h o l itself a n d o t h e r u n k n o w n factors o r h y p e r o s m o l a l i t y d u e to h y p e r n a t r a e m i a b u t also e l e c t r o l y t e d i s t u r b a n c e s in general that l e a d to b r a i n - s t e m d y s f u n c t i o n m a y p l a y an essential role in the p a t h o g e n e s i s of C P M . In t h e p r e s e n t cases s e v e r e h y p o k a l a e m i a was c o r r e c t e d r a p i d l y to prev e n t c a r d i a c failure. T h e r a p i d c o r r e c t i o n p a r a l l e l e d the i m p r o v e m e n t o f c o n s c i o u s n e s s in o n e p a t i e n t b u t the o t h e r p a t i e n t d e t e r i o r a t e d further. B o t h p a t i e n t s , however, s h o w e d a n e a r l y c o m p l e t e clinical r e c o v e r y . Since the exact p a t h o l o g y of p o n t i n e d y s f u n c t i o n and subseq u e n t m y e l i n o l y s i s are not k n o w n , the c u r r e n t p r a g m a tic t h e r a p y s h o u l d involve slow c o r r e c t i o n of h y p e r - o r h y p o n a t r a e m i a a n d a m o r e r a p i d c o r r e c t i o n (within 48 h) of h y p o k a l a e m i a a n d any v i t a m i n deficiencies. H o w e v e r , f u r t h e r studies are n e e d e d for a m o r e f u n d a m e n t a l und e r s t a n d i n g of the p a t h o p h y s i o l o g y u n d e r l y i n g C P M .
References 1. Adams RD, Victor M, Mancall EL (i959) Central pontine myelinolysis: a hitherto undescribed disease occurring in alcoholic and malnourished patients. Arch Neurol Psychiatry 81 : 154-172 2. Berlit P (1986) Die zentrale pontine Myelinolyse. Nervenarzt 57 : 624-633 3. Brunner JE, Redmond JM, Haggar AM, Stanton BE (1988) Central pontine myelinolysis after rapid correction of hyponatremia: a magnetic resonance study. Ann Neurol 23:389-391 4. Colmant HJ, Gocht A (1987) Central pontine and extrapontine myelinolysis: a report of 58 cases. Clin Neuropathol 6: 262-270 5. Deppe A, Haan J (i986) Zentrale pontine Myelinolyse bei Alkoholismus. Nervenarzt 57:609-612 6. DeWitt LD, Buonanno FS, Kistler JP, Zeffiro T, DeLaPaz RL, Brady TJ, Rosen BR, Pykett LP (1984) Central pontine myelinolysis: demonstration by nuclear magnetic resonance. Neurology 34 : 570-576 7. Estol CJ, Faris AA, Martinez A J, Ahdab-Barmada M (1989) Central pontine myelinolysis after liver transplantation. Neurology 39 : 493-498 8. Illowsky BP, Laureno R (1987) Encephalopathy and myelinolysis after rapid correction of hyponatremia. Brain 110:855867 9. Messert B, Orrison WW, Hawkins MJ, Quaglieri CE (1979) Central pontine myelinolysis. Neurology 29:147-160 10. Miller GM, Baker HL, Okazaki H, Whisnant JP (1988) Central pontine myetinolysis and its imitators: MR findings. Radiology 168 : 795-802 1l. Noremberg MD, Leslie KO, Robertson AS (1981) Association between rise in serum sodium and central pontine myelinolysis. Ann Neurol 11:128-135 12. Pfister HW, Einhäupl KM, Brandt T (1985) Mild central pontine myelinolysis: a frequently undetected syndrome. Eur Arch Psychiatry Neurol Sci 235:134-139 13. Schroth G (1984) Clinical and CT confirmed recovery from central pontine myelinolytes. Neuroradiology 26 : 149-151 14. Takeda K, Sakuta Mù Saeki F (1989) Central pontine myelinolysis diagnosed by magnetic resonance imaging. Ann Neurol 36:310-311
Journal of
Neurology © Springer-Verlag 1990
Central pontine myelinolysis associated with iow potassium levels in alcoholism M. Bähr 1, N. Sommer 1, D. Petersen:, H. Wiethölter 1, and J. Dichgans ~ Departments of 1Neurology and 2Neuroradiology, University of Tübingen, Tübingen, Federal Republic of Germany Received February 16, 1990 / Accepted March 1, 1990
Summary. Two patients with chronic alcohol abuse and central pontine myelinolysis are described. One developed a Korsakoff syndrome 2 days before admission to our hospital and the other showed signs of a incipient delirium without Korsakoff syndrome. Diagnosis of incipient central pontine myelinolysis was based on acute brain-stem dysfunction, serum electrolyte disturbances, malnutrition with vitamin B1 (thiamine), B6 (pyridoxine) and B12 (cyanocobalamine) deficiency in combination with typical neuroradiological findings. H y p o k a l a e m i a but no disturbance in serum sodium levels was found in both patients. After correction of h y p o k a l a e m i a and vitamin deficiency the patients showed complete recovery of neurological and neuropsychological function. The findings are interpreted as suggesting that disturbances in serum potassium levels as well as rapid correction of h y p o n a t r a e m i a may be associated with pontine swelling and dysfunction which, if undetected, leads to central pontine myelinolysis.
Key words: Central pontine myelinolysis - Serum electrolytes - Magnetic resonance imaging - Vitamin
Introduction Since central pontine myelinolysis (CPM) was first described as a clinical entity [1] it has b e e n considered that rapid changes in serum electrolyte levels might be pathogenetically involved in its development [6, 8-10]. Experimental and clinical data [7] have suggested that CPM might be related to rapid correction of a preceding hyponatraemia, hut n o r m o n a t r a e m i c and hypernatraemic patients have also been described [3, 5, 6] and the exact mechanism leading to the acute brain-stem dysfunction is still unknown. CPM predominantly occurs in patients with chronic alcohol abuse [3, 4, 8], liver disease [3, 6] and malnutrition [1, 3]. Clinically acute brain-stem dysfunction together with serum electrolyte disturbances Offprint requests to: M. Bähr, Neurologische Universitätsklinik, Hoppe-Seylerstrasse 3, D-7400 Tübingen, Federal Republic of Germany
and typical neuroradiological findings [2, 5, 11, 13, 14] can lead to the intra vitam diagnosis of a CPM, Early detection and t r e a t m e n t of a CPM [10, 12], which often follows delirium tremens, seem to be critical for the clinical outcome of patients. The purpose of the present p a p e r is to point out that not only disturbances of serum sodium but also those of serum potassium in combination with malnutrition and subsequent vitamin-B deficiency due to chronic alcohol abuse may be associated with brain-stem lesions that can be detected by c o m p u t e d t o m o g r a p h y (CT) and magnetic resonance imaging (MRI). M o r e o v e r , the cases presented seem to indicate that the early and rapid correction of hypokalaemia (unlike the slow correction of low serum sodium levels) and malnutrition m a y substantially improve the clinical outcome of patients with incipient CPM.
Case reports Case 1 A 59-year-old right-handed male patient was admitted to our hospital because of an acute Korsakoff syndrome with eonfabulation, memory impairment and disorientation. Within hours coma developed. Neurological examination showed an impaired optokinetic nystagmus and bilateral latent signs of a brain-stem dysfunetion. Serum electrolyte analysis revealed severe hypokalaemia of less than 3 mmol/1 and low levels of vitamins B1, B6, and BI2. Serum sodium levels were always normal (137-139mmol/1). Initial CT showed brain-stem swelling and a generalized hypodensity which extended from the pons to paraventricular areas. MRI 3 days after admission showed an irregular pattern of hyperintensities of the white matter, not particularly in the pontine region, compatible with chronic subcortical vascular lesions. On follow-up MRI 2 weeks later the subcortieal lesions were unchanged, hut within the pons a large, triangular-shaped hyperintensity on T2-weighted images was seen (Fig. 1). Initially the patient, as examined by transcranial Doppler sonography, had a reduced blood flow of the vertebral and basilar arteries, probably due to the swelling of the brain-stem. Correction of serum potassium levels and malnutrition by infusion therapy led to quick recovery of consciousness. At the time of discharge from the hospital the patient had no remaining neurological or neuropsychological deficits.
276
Fig.1. Corresponding T2-weighted axial MR images (SE 2.0/90) at 3 days (a) and at 20 days after admission to the hospital (b). a A completely normal brain-stem was found, b MRI 17 days later showed a central pontine hyperintense lesion
Case 2 A 32-year-old right-handed female alcoholic was admitted to the hospital with impaired consciousness after abrupt alcohol abstinence of her own choice. The patient developed a severe hypokalaemia of 2.6 mmol/1 serum potassium with normal serum sodium levels (133mmol/l) but no evidence of malnutrition. Electrolyte disturbance was corrected within 36 h but the neurological symptoms deteriorated with impaired consciousness, dysarthria, difficulty in swallowing, areflexia and sensory ataxia. She was therelore transferred to an intensive care unit, where she developed myoclonic jerks in all limbs and in facial muscles. The diagnosis of CPM was made clinically. CT and MRI did not show any pontine lesions. During the phase of clinical recovery (about 2 weeks after admission) MRI showed a well-defined lesion of 6-8 mm in diameter in the central pons with a bright signal on T2-weighted axial images and no brain-stem swelling. At the time of discharge the patient only showed slight ataxia and no brain-stem dysfunction.
Discussion W e h a v e d e s c r i b e d 2 p a t i e n t s with a l c o h o l a b u s e who dev e l o p e d a c u t e b r a i n - s t e m d y s f u n c t i o n a s s o c i a t e d with sev e r e s e r u m p o t a s s i u m d i s t u r b a n c e . C T a n d M R I conf i r m e d a lesion o f the p o n s at l a t e r stages. Clinical a n d neurological data (impaired consciousness, impaired opt o k i n e t i c s a n d t e t r a p a r e s i s in c o m b i n a t i o n with s e r u m e l e c t r o l y t e d i s t u r b a n c e s ) l e d to the d i a g n o s i s of i n c i p i e n t CPM. T h e o n s e t o f s y m p t o m s in the two p a t i e n t s with alc o h o l i s m c o r r e l a t e d weil with h y p o k a l a e m i a a n d m a l n u trition. T h e s e findings suggest a p o s s i b l e i n v o l v e m e n t of s e r u m p o t a s s i u m d i s t u r b a n c e s w i t h o u t h y p o n a t r a e m i a in t h e p a t h o g e n e s i s of C P M . M o s t p r e v i o u s r e p o r t s have f o c u s e d o n the a s s o c i a t i o n b e t w e e n h y p o n a t r a e m i a a n d C P M [3, 7, 8, 11]. In p a r t i c u l a r , t h e r a p i d rise of s e r u m s o d i u m levels o r o v e r c o r r e c t i o n o f h y p o n a t r a e m i a which m a y l e a d to h y p e r o s m o l a l i t y h a v e b e e n d e s c r i b e d to be p a t h o g e n e t i c a l l y i n v o l v e d in C P M [7, 8, 11]. T h e r e h a v e b e e n s e v e r a l r e p o r t s , h o w e v e r , o f C P M in n o r m o n a t r a e m i c o r p r i m ä r i l y h y p e r n a t r a e m i c p a t i e n t s . B o t h norm o n a t r a e m i c a n d h y p o n a t r a e m i c p a t i e n t s with h y p o k a l a e m i a h a v e also b e e n d e s c r i b e d [3, 6]. W h e t h e r the p o n -
tine dysfunction and s u b s e q u e n t m y e l i n o l y t i c lesions are r e l a t e d to shifts in s e r u m o s m o l a l i t y o r m o r e specifically l i n k e d to c h a n g e s in i n t r a c e l l u l a r s o d i u m o r p o t a s s i u m levels t h e r e f o r e r e m a i n s to b e e l u c i d a t e d . T h e o b s e r v a t i o n , h o w e v e r , that a h e t e r o g e n e i t y of s e r u m e l e c t r o l y t e d i s t u r b a n c e s is a s s o c i a t e d with C P M indicates that not only the toxic effects of a l c o h o l itself a n d o t h e r u n k n o w n factors o r h y p e r o s m o l a l i t y d u e to h y p e r n a t r a e m i a b u t also e l e c t r o l y t e d i s t u r b a n c e s in general that l e a d to b r a i n - s t e m d y s f u n c t i o n m a y p l a y an essential role in the p a t h o g e n e s i s of C P M . In t h e p r e s e n t cases s e v e r e h y p o k a l a e m i a was c o r r e c t e d r a p i d l y to prev e n t c a r d i a c failure. T h e r a p i d c o r r e c t i o n p a r a l l e l e d the i m p r o v e m e n t o f c o n s c i o u s n e s s in o n e p a t i e n t b u t the o t h e r p a t i e n t d e t e r i o r a t e d further. B o t h p a t i e n t s , however, s h o w e d a n e a r l y c o m p l e t e clinical r e c o v e r y . Since the exact p a t h o l o g y of p o n t i n e d y s f u n c t i o n and subseq u e n t m y e l i n o l y s i s are not k n o w n , the c u r r e n t p r a g m a tic t h e r a p y s h o u l d involve slow c o r r e c t i o n of h y p e r - o r h y p o n a t r a e m i a a n d a m o r e r a p i d c o r r e c t i o n (within 48 h) of h y p o k a l a e m i a a n d any v i t a m i n deficiencies. H o w e v e r , f u r t h e r studies are n e e d e d for a m o r e f u n d a m e n t a l und e r s t a n d i n g of the p a t h o p h y s i o l o g y u n d e r l y i n g C P M .
References 1. Adams RD, Victor M, Mancall EL (i959) Central pontine myelinolysis: a hitherto undescribed disease occurring in alcoholic and malnourished patients. Arch Neurol Psychiatry 81 : 154-172 2. Berlit P (1986) Die zentrale pontine Myelinolyse. Nervenarzt 57 : 624-633 3. Brunner JE, Redmond JM, Haggar AM, Stanton BE (1988) Central pontine myelinolysis after rapid correction of hyponatremia: a magnetic resonance study. Ann Neurol 23:389-391 4. Colmant HJ, Gocht A (1987) Central pontine and extrapontine myelinolysis: a report of 58 cases. Clin Neuropathol 6: 262-270 5. Deppe A, Haan J (i986) Zentrale pontine Myelinolyse bei Alkoholismus. Nervenarzt 57:609-612 6. DeWitt LD, Buonanno FS, Kistler JP, Zeffiro T, DeLaPaz RL, Brady TJ, Rosen BR, Pykett LP (1984) Central pontine myelinolysis: demonstration by nuclear magnetic resonance. Neurology 34 : 570-576 7. Estol CJ, Faris AA, Martinez A J, Ahdab-Barmada M (1989) Central pontine myelinolysis after liver transplantation. Neurology 39 : 493-498 8. Illowsky BP, Laureno R (1987) Encephalopathy and myelinolysis after rapid correction of hyponatremia. Brain 110:855867 9. Messert B, Orrison WW, Hawkins MJ, Quaglieri CE (1979) Central pontine myelinolysis. Neurology 29:147-160 10. Miller GM, Baker HL, Okazaki H, Whisnant JP (1988) Central pontine myetinolysis and its imitators: MR findings. Radiology 168 : 795-802 1l. Noremberg MD, Leslie KO, Robertson AS (1981) Association between rise in serum sodium and central pontine myelinolysis. Ann Neurol 11:128-135 12. Pfister HW, Einhäupl KM, Brandt T (1985) Mild central pontine myelinolysis: a frequently undetected syndrome. Eur Arch Psychiatry Neurol Sci 235:134-139 13. Schroth G (1984) Clinical and CT confirmed recovery from central pontine myelinolytes. Neuroradiology 26 : 149-151 14. Takeda K, Sakuta Mù Saeki F (1989) Central pontine myelinolysis diagnosed by magnetic resonance imaging. Ann Neurol 36:310-311
