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Posterior reversible leukoencephalopathy syndrome: possible relation to licorice
European Journal of Radiology Extra 46 (2003) 83 /85 http://intl.elsevierhealth.com/journals/ejrx
Posterior reversible leukoencephalopathy syndrome: possible relation to licorice Joong-Seok Kim a, Seong-Woo Chung a,*, Tae-Ick Chung a, Jeong-Wook Park a, Kwang-Soo Lee a, Jae-Hee Lee b a
Department of Neurology, College of Medicine, Pupyoung Our Lady of Mercy Hospital, Catholic University Medical College, #665, Pupyoung Dong, Pupyoung Gu, Inchon 430-720, South Korea b Department of Radiology, College of Medicine, Pupyoung Our Lady of Mercy Hospital, Catholic University Medical College, #665, Pupyoung Dong, Pupyoung Gu, Inchon 430-720, South Korea Received 7 February 2002; received in revised form 5 April 2002; accepted 8 April 2002
Abstract We describe a patient with posterior reversible leukoencephalopathy syndrome (PRLS) after receiving a prescription of herbs containing licorice as a tonic medicine. The typical reversible MRI findings following the consumption of licorice suggests a possible relationship between licorice ingestion, hypertension, and PRLS, despite the fact that a cause-and-effect relationship cannot be automatically inferred. # 2002 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Posterior reversible leukoencephalopathy syndrome; Licorice; Hypertension; Pseudoaldosteronism
1. Introduction Posterior reversible leukoencephalopathy syndrome (PRLS) is a newly recognized neurological disorder, characterized predominantly by white matter edema affecting the occipital and posterior parietal lobes of the brain. Although the exact etiology is not known precisely, the major causes of this syndrome are as follows; hypertensive encephalopathy, eclampsia, the use of cytotoxic drugs or immunosuppressive agents, and renal insufficiency [1]. In clinics practicing traditional oriental medicine, licorice has been used routinely combined with various herbs, serving as something of ‘a Jack-of-all-trades’. Licorice can inhibit 11b-hydroxysteroid dehydrogenase (11b-HSD) both in-vivo and in-vitro [2]. 11b-HCD inactivates corticosterone and cortisol, allowing the more abundant glucocorticoids access to the mineralocorticoid receptor in the kidney, where they act as
* Corresponding author. Tel.: /82-32-510-5664; fax.: /82-2-5999686 E-mail address: [email protected] (S.-W. Chung).
mineralocorticoids. The mineralocorticoid excess syndrome of patients ingesting a large amount of licorice or its derivatives produces a central hypertensinogenic effect [3]. Hypertensive encephalopathy following licorice ingestion has rarely been described in humans, with the exception of one case in the literature [4]. We experienced a case of PRLS associated with mild hypertension after a doctor of oriental medicine prescribed herbs containing licorice and discuss a possible relationship to a licorice derivative.
2. Case report A 13-year-old male patient was admitted to our hospital due to episodic tensive headache, dysarthria and left hemiparesis. During 5 days before admission, the boy had taken herbs as a tonic medicine, herbs which contained licorice, elecampane, ginger, jujube, ginseng and other unknown adjuvants. The amount of licorice extract ingested by the child was probably about 1.4 g/day, as judged by the manufacturer’s formula for the confection. Two days before admission, the patient experienced four episodes of dysarthria and/or left
1571-4675/03/$ - see front matter # 2002 Elsevier Science Ireland Ltd. All rights reserved. doi:10.1016/S1571-4675(03)00052-X
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J.-S. Kim et al. / European Journal of Radiology Extra 46 (2003) 83 /85
hemiparesis. These attacks were sudden, lasting 30 /60 min and occurring one to two times a day. There was no personal or family history of medical or neurological diseases. On examination, he was alert and oriented, with a BP of 140/90 mmHg, a regular heart beat of 96 beats/min, and a temperature of 36.8 8C. The physical and neurological examination did not demonstrate any pathologic findings. The results of laboratory tests were as follows; WBC 7100/mm3, hemoglobin 14.1 g/dl, platelets 237,000/mm3,
erythrocyte sedimentation rate 10/mmHr, urea nitrogen 9.7 mg/dl, serum creatinine 0.7 mg/dl, sodium/potassium 141/3.3 mEq/l, T3 1.74 ng/ml, T4 9.58 mg/dl, TSH 2.47 mg/ml, serum cortisol 3.6 mg/dl (3 /132), ACTH 8.3 pg/ ml (9 /52), 17-hydroxycorticosteroid 4.10 mg/day (2 / 10), Renin 2.81 ng/ml/h (0.68 /1.36), aldosterone 90.41 pg/ml (10 /160), lactic acid 14.8 mg/dl (4.5 /19.8), very long chain fatty acid 0.010 (below 0.033), and arylsulfatase A 1.075 nmol/min/mg protein (0.5 /1.5). Other tests, including those for autoantibodies and coagulation factor, were normal.
Fig. 1. On the first day following admission, high signal areas were seen in both the peritrigonal and supraventricular white matter on T2-weighted images. The diffusion-weighted images (a) showed more extensive symmetrical high signal intensity and the apparent diffusion coefficient mapping (b) showed decreased signal change in the aforementioned areas. Eight days later, almost all the lesions had resolved with the exception of subtle signal changes (c: diffusion-weighted; d: ADC mapping).
J.-S. Kim et al. / European Journal of Radiology Extra 46 (2003) 83 /85
T2-weighted MR and fluid-attenuated inversion-recovery images disclosed diffuse symmetric high signal intensities in both the peritrigonal and supraventricular white matter, while the T1-weighted and the postcontrast T1-weighted images were normal. The diffusion-weighted images showed a more extensive symmetrical high signal intensity (Fig. 1a) and the apparent diffusion coefficient mapping showed decreased signal change in the aforementioned areas (Fig. 1b). During the follow-up periods, arterial pressure was between 110/60 and 150/90, with a peak at 170/100 and hypertension improving spontaneously. Eight days later, we conducted a follow-up MRI that showed much improved findings (Fig. 1c,d).
85
ism, including hypokalemia and hypertension, produced by excessive licorice consumption has been attributed to the inhibition of 11b-HCD, allowing the more abundant cortisol and corticosterone access to the mineralocorticoid receptors in the kidney [10]. It is of course possible that PRLS may be unrelated to licorice. In addition, some unknown adjuvants cannot be ruled out in relation to this condition. However, additional clinical evidences of the mild hypokalemia, mild hypertension and suppression of the pituitary/ adrenal axis in this patient support sufficient correlations with manifestations caused by licorice. Therefore, we think that exposure to licorice may result in PRLS, despite the fact that a cause-and-effect relationship usually cannot be established with certainty.
3. Discussion PRLS may result from a rapid rise in blood pressure that overcomes the normal autoregulation of cerebral blood flow. This disturbance of autoregulation produces dilatation of cerebral arterioles with an opening of endothelial tight junctions and leakage of plasma and red cells into the extracellular space, producing cerebral edema. However, there has been a debate over vasogenic edema as a possible pathology [5,6]. Another hypothesis explaining this condition is vasospasm secondary to sudden and severe rises in blood pressure and ischemia of the brain; ischemic damage to brain tissue first produces cytotoxic edema and then extracellular edema [7,8]. As in our case, a T2-weighted MRI shows high signal areas selectively in the white matter, often mainly at the parieto-occipital lobes. These lesions likely represent cytotoxic edema, reflecting a diffuse ischemic change due to vasospasm. These findings are typical of PRLS [9]. The occurrence of unusual reversible signal changes in our patient following the consumption of licorice suggests a possible relationship to licorice ingestion, hypertension, and PRLS. The pseudohyperaldosteron-
References [1] Garg RK. Posterior leukoencephalopathy syndrome. Postgrad Med 2001;77:24 /8. [2] Whorwood CB, Sheppard MC, Stewart PM. Licorice inhibits 11b-hydroxysteroid dehydrogenase messenger ribonucleic acid levels and potentiates glucocorticoid hormone action. Endocrinology 1993;132:2287 /92. [3] Gomez-Sanchez EP, Gomez-Sanchez CE. Central hypertensinogenic effects of glycyrrhizic acid and carbenoxolone. Am J Physiol 1992;263:E1125 /30. [4] McNicholl B, Kilroy MK. Transient hypertensive encephalopathy: possible relation to licorice. J Pediatr 1969;74:963 /4. [5] Johansson B. Regional cerebral blood flow in acute experimental hypertension. Acta Neurol Scand 1974;50:366 /72. [6] Johanson B. The blood brain barrier and cerebral blood flow in acute hypertension. Acta Neurol Scand 1983;678:S107 /12. [7] Geraghty J, Huch D, Robert M, Vinters H. Fatal puerperal cerebral spasm and stroke in young women. Neurology 1991;41:1145 /7. [8] Trommer BL, Honer D, Mikhael MA. Cerebral vasospasm and eclampsia. Stroke 1988;19:326 /9. [9] Ay H, Buonanno FS, Schaefer PW, Le DA, Wang B, Gonzalez RG, Koroshetz WJ. Posterior leukoencephalopathy without severe hypertension. Neurology 1998;51:1369 /76. [10] Edward CRW, Stewart PM. The cortisol /cortisone shuttle and the apparent specificity of glucocorticoid and mineralocorticoid receptors. J Steroid Biochem Mol Biol 1991;39:859 /65.
Posterior reversible leukoencephalopathy syndrome: possible relation to licorice Joong-Seok Kim a, Seong-Woo Chung a,*, Tae-Ick Chung a, Jeong-Wook Park a, Kwang-Soo Lee a, Jae-Hee Lee b a
Department of Neurology, College of Medicine, Pupyoung Our Lady of Mercy Hospital, Catholic University Medical College, #665, Pupyoung Dong, Pupyoung Gu, Inchon 430-720, South Korea b Department of Radiology, College of Medicine, Pupyoung Our Lady of Mercy Hospital, Catholic University Medical College, #665, Pupyoung Dong, Pupyoung Gu, Inchon 430-720, South Korea Received 7 February 2002; received in revised form 5 April 2002; accepted 8 April 2002
Abstract We describe a patient with posterior reversible leukoencephalopathy syndrome (PRLS) after receiving a prescription of herbs containing licorice as a tonic medicine. The typical reversible MRI findings following the consumption of licorice suggests a possible relationship between licorice ingestion, hypertension, and PRLS, despite the fact that a cause-and-effect relationship cannot be automatically inferred. # 2002 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Posterior reversible leukoencephalopathy syndrome; Licorice; Hypertension; Pseudoaldosteronism
1. Introduction Posterior reversible leukoencephalopathy syndrome (PRLS) is a newly recognized neurological disorder, characterized predominantly by white matter edema affecting the occipital and posterior parietal lobes of the brain. Although the exact etiology is not known precisely, the major causes of this syndrome are as follows; hypertensive encephalopathy, eclampsia, the use of cytotoxic drugs or immunosuppressive agents, and renal insufficiency [1]. In clinics practicing traditional oriental medicine, licorice has been used routinely combined with various herbs, serving as something of ‘a Jack-of-all-trades’. Licorice can inhibit 11b-hydroxysteroid dehydrogenase (11b-HSD) both in-vivo and in-vitro [2]. 11b-HCD inactivates corticosterone and cortisol, allowing the more abundant glucocorticoids access to the mineralocorticoid receptor in the kidney, where they act as
* Corresponding author. Tel.: /82-32-510-5664; fax.: /82-2-5999686 E-mail address: [email protected] (S.-W. Chung).
mineralocorticoids. The mineralocorticoid excess syndrome of patients ingesting a large amount of licorice or its derivatives produces a central hypertensinogenic effect [3]. Hypertensive encephalopathy following licorice ingestion has rarely been described in humans, with the exception of one case in the literature [4]. We experienced a case of PRLS associated with mild hypertension after a doctor of oriental medicine prescribed herbs containing licorice and discuss a possible relationship to a licorice derivative.
2. Case report A 13-year-old male patient was admitted to our hospital due to episodic tensive headache, dysarthria and left hemiparesis. During 5 days before admission, the boy had taken herbs as a tonic medicine, herbs which contained licorice, elecampane, ginger, jujube, ginseng and other unknown adjuvants. The amount of licorice extract ingested by the child was probably about 1.4 g/day, as judged by the manufacturer’s formula for the confection. Two days before admission, the patient experienced four episodes of dysarthria and/or left
1571-4675/03/$ - see front matter # 2002 Elsevier Science Ireland Ltd. All rights reserved. doi:10.1016/S1571-4675(03)00052-X
84
J.-S. Kim et al. / European Journal of Radiology Extra 46 (2003) 83 /85
hemiparesis. These attacks were sudden, lasting 30 /60 min and occurring one to two times a day. There was no personal or family history of medical or neurological diseases. On examination, he was alert and oriented, with a BP of 140/90 mmHg, a regular heart beat of 96 beats/min, and a temperature of 36.8 8C. The physical and neurological examination did not demonstrate any pathologic findings. The results of laboratory tests were as follows; WBC 7100/mm3, hemoglobin 14.1 g/dl, platelets 237,000/mm3,
erythrocyte sedimentation rate 10/mmHr, urea nitrogen 9.7 mg/dl, serum creatinine 0.7 mg/dl, sodium/potassium 141/3.3 mEq/l, T3 1.74 ng/ml, T4 9.58 mg/dl, TSH 2.47 mg/ml, serum cortisol 3.6 mg/dl (3 /132), ACTH 8.3 pg/ ml (9 /52), 17-hydroxycorticosteroid 4.10 mg/day (2 / 10), Renin 2.81 ng/ml/h (0.68 /1.36), aldosterone 90.41 pg/ml (10 /160), lactic acid 14.8 mg/dl (4.5 /19.8), very long chain fatty acid 0.010 (below 0.033), and arylsulfatase A 1.075 nmol/min/mg protein (0.5 /1.5). Other tests, including those for autoantibodies and coagulation factor, were normal.
Fig. 1. On the first day following admission, high signal areas were seen in both the peritrigonal and supraventricular white matter on T2-weighted images. The diffusion-weighted images (a) showed more extensive symmetrical high signal intensity and the apparent diffusion coefficient mapping (b) showed decreased signal change in the aforementioned areas. Eight days later, almost all the lesions had resolved with the exception of subtle signal changes (c: diffusion-weighted; d: ADC mapping).
J.-S. Kim et al. / European Journal of Radiology Extra 46 (2003) 83 /85
T2-weighted MR and fluid-attenuated inversion-recovery images disclosed diffuse symmetric high signal intensities in both the peritrigonal and supraventricular white matter, while the T1-weighted and the postcontrast T1-weighted images were normal. The diffusion-weighted images showed a more extensive symmetrical high signal intensity (Fig. 1a) and the apparent diffusion coefficient mapping showed decreased signal change in the aforementioned areas (Fig. 1b). During the follow-up periods, arterial pressure was between 110/60 and 150/90, with a peak at 170/100 and hypertension improving spontaneously. Eight days later, we conducted a follow-up MRI that showed much improved findings (Fig. 1c,d).
85
ism, including hypokalemia and hypertension, produced by excessive licorice consumption has been attributed to the inhibition of 11b-HCD, allowing the more abundant cortisol and corticosterone access to the mineralocorticoid receptors in the kidney [10]. It is of course possible that PRLS may be unrelated to licorice. In addition, some unknown adjuvants cannot be ruled out in relation to this condition. However, additional clinical evidences of the mild hypokalemia, mild hypertension and suppression of the pituitary/ adrenal axis in this patient support sufficient correlations with manifestations caused by licorice. Therefore, we think that exposure to licorice may result in PRLS, despite the fact that a cause-and-effect relationship usually cannot be established with certainty.
3. Discussion PRLS may result from a rapid rise in blood pressure that overcomes the normal autoregulation of cerebral blood flow. This disturbance of autoregulation produces dilatation of cerebral arterioles with an opening of endothelial tight junctions and leakage of plasma and red cells into the extracellular space, producing cerebral edema. However, there has been a debate over vasogenic edema as a possible pathology [5,6]. Another hypothesis explaining this condition is vasospasm secondary to sudden and severe rises in blood pressure and ischemia of the brain; ischemic damage to brain tissue first produces cytotoxic edema and then extracellular edema [7,8]. As in our case, a T2-weighted MRI shows high signal areas selectively in the white matter, often mainly at the parieto-occipital lobes. These lesions likely represent cytotoxic edema, reflecting a diffuse ischemic change due to vasospasm. These findings are typical of PRLS [9]. The occurrence of unusual reversible signal changes in our patient following the consumption of licorice suggests a possible relationship to licorice ingestion, hypertension, and PRLS. The pseudohyperaldosteron-
References [1] Garg RK. Posterior leukoencephalopathy syndrome. Postgrad Med 2001;77:24 /8. [2] Whorwood CB, Sheppard MC, Stewart PM. Licorice inhibits 11b-hydroxysteroid dehydrogenase messenger ribonucleic acid levels and potentiates glucocorticoid hormone action. Endocrinology 1993;132:2287 /92. [3] Gomez-Sanchez EP, Gomez-Sanchez CE. Central hypertensinogenic effects of glycyrrhizic acid and carbenoxolone. Am J Physiol 1992;263:E1125 /30. [4] McNicholl B, Kilroy MK. Transient hypertensive encephalopathy: possible relation to licorice. J Pediatr 1969;74:963 /4. [5] Johansson B. Regional cerebral blood flow in acute experimental hypertension. Acta Neurol Scand 1974;50:366 /72. [6] Johanson B. The blood brain barrier and cerebral blood flow in acute hypertension. Acta Neurol Scand 1983;678:S107 /12. [7] Geraghty J, Huch D, Robert M, Vinters H. Fatal puerperal cerebral spasm and stroke in young women. Neurology 1991;41:1145 /7. [8] Trommer BL, Honer D, Mikhael MA. Cerebral vasospasm and eclampsia. Stroke 1988;19:326 /9. [9] Ay H, Buonanno FS, Schaefer PW, Le DA, Wang B, Gonzalez RG, Koroshetz WJ. Posterior leukoencephalopathy without severe hypertension. Neurology 1998;51:1369 /76. [10] Edward CRW, Stewart PM. The cortisol /cortisone shuttle and the apparent specificity of glucocorticoid and mineralocorticoid receptors. J Steroid Biochem Mol Biol 1991;39:859 /65.