Ir J Med Sci DOI 10.1007/s11845-014-1214-0
CASE BASED REVIEW
Posterior reversible encephalopathy syndrome (PRES) associated with liquorice consumption K. O’Connell • J. Kinsella • C. McMahon J. Holian • S. O’Riordan
•
Received: 29 May 2014 / Accepted: 14 October 2014 Ó Royal Academy of Medicine in Ireland 2014
Abstract Importance Posterior reversible encephalopathy syndrome (PRES) is a medical emergency but prompt recognition, early institution of supportive care and identifying and removing potential triggers are associated with a good clinical outcome. We report an unusual case of PRES associated with liquorice consumption. Observations A 56-year-old lady presented with thunderclap headache, visual disturbance and a generalised tonic–clonic seizure. Blood pressure on admission was markedly elevated but improved within 24 h. Cranial CT and lumbar puncture were normal (no xanthochromia). She had hypokalaemia. Cranial MRI revealed abnormalities in the occipital lobes consistent with PRES. There was no evidence of restricted diffusion or vasoconstriction. Follow-up MRI 3 weeks later demonstrated complete resolution. On direct questioning she revealed in recent months she had habitually eaten liquorice sweets each day; they were ‘‘on special offer’’ in her local shop. Conclusion and relevance Liquorice contains a biologically active compound glycyrrhizic acid which inhibits 11b hydroxysteroid dehydrogenase. Excessive liquorice consumption can cause mineralocorticoid excess and has been
K. O’Connell (&) J. Kinsella S. O’Riordan Department of Neurology, St Vincent’s University Hospital, Elm Park, Dublin 4, Ireland e-mail: [email protected] C. McMahon Department of Radiology, St Vincent’s University Hospital, Dublin, Ireland J. Holian Department of Nephrology, St Vincent’s University Hospital, Dublin, Ireland
recently reported to cause PRES. We propose that in the absence of other triggers, frequent liquorice consumption precipitated the development of PRES in our patient and should be considered as a possible cause of this condition. Keywords Posterior reversible encephalopathy syndrome Liquorice Hypertension
Case report A 56-year-old woman presented to our hospital with acute onset thunderclap headache predominantly affecting the left fronto-temporal region before extending to involve the occipital regions bilaterally. She rated the pain as ten out of ten in severity. She had associated nausea but no vomiting. She described visual disturbance with zig-zag lines and then more vivid colours predominantly in her right visual field. While in the emergency department she had a generalised tonic–clonic seizure that resolved spontaneously after 60 s. Her only preceding medical history was of benign colonic polyps and mild hypertension for a number of years that was well controlled with low-dose ACE inhibitor. On examination, she was alert but disoriented to place and time in keeping with post-ictal confusion. Blood pressure was elevated at 210/80 mm Hg but this settled within 24 h without additional antihypertensive treatment. There was no clinical evidence of raised intracranial pressure. Visual fields were full and the remainder of the neurological examination was normal. CT brain was normal. CSF contained 4 white cells/cm2, 222 red cells/cm2, protein 0.43 g/L, glucose 4.6 mEq/L (serum 8.9 mEq/L) and there was no xanthochromia. Opening pressure was 160 mm of water. An initial peripheral leucocytosis quickly normalised and ESR and
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Ir J Med Sci
Fig. 1 Axial FLAIR sequence MRI taken on admission showing hyperintense lesions predominantly affecting the occipital lobes bilaterally, which would be in keeping with PRES
Fig. 2 Axial FLAIR sequence MRI taken 3 weeks after presentation showing resolution of the previously documented changes
CRP were normal. She was hypokalaemic at 3.0 mEq/L (range 3.5–5.0) and sodium was at the upper limit of normal at 145 mEq/L (range 136–145). Electroencephalogram (EEG) was performed approximately 36 h after witnessed seizure and showed evidence of intermittent, 4–7 per second focal sharpened activity involving the left anterior temporal region without electrographic seizures. Cranial MRI (Fig. 1) revealed foci of T2 and FLAIR hyperintensity predominantly in the occipital lobes, consistent with posterior reversible encephalopathy syndrome (PRES). No areas of restricted diffusion were noted.
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Intracranial MR angiogram showed no evidence of vasoconstriction. Her headache settled during the first 24 h of admission but visual disturbance persisted for 48 h with ongoing blurred vision affecting both eyes and the appearance of letters in her visual field. She was commenced on phenytoin and clobazam and she had no further generalised seizures. Her blood pressure remained within normal limits on her regular dose of ACE inhibitor. Follow-up MRI brain at 3 weeks (Fig. 2) showed complete resolution of the previously documented
Ir J Med Sci
abnormalities. Anticonvulsant treatment was stopped after 2 months and she remains seizure free at 18-month followup. On direct questioning she revealed that in recent months she had habitually eaten liquorice sweets each day as they were ‘‘on special offer’’ in her local shop. In view of the supportive biochemical findings and in the absence of other potential triggers we diagnosed posterior reversible encephalopathy syndrome (PRES) associated with liquorice consumption. The patient was advised to avoid further liquorice consumption.
Discussion Posterior reversible encephalopathy syndrome, originally described by Hinchey and colleagues in 1996 [1], comprises a clinical syndrome of headache, altered mental status, seizures and visual symptoms which can include cortical blindness, blurred vision, visual neglect and visual hallucinations. The pathogenesis is not fully understood but it has been proposed that endothelial damage either as a direct effect of certain medications or due to sudden elevations in blood pressure causes a breakdown of the blood– brain barrier. This gives rise to areas of cerebral oedema and petechial haemorrhages. Imaging studies demonstrate a predominantly posterior leukoencephalopathy. There have been many reported associations or triggers including renal impairment, immunosuppression, chemotherapy and eclampsia [2]. Acute elevation in systemic blood pressure is seen in the majority of cases [1–3] making it a significant aetiological factor. Liquorice contains a biologically active compound, glycyrrhizic acid, which inhibits 11b hydroxysteroid dehydrogenase, the enzyme responsible for the conversion of cortisol to cortisone [4]. When consumed in large quantities, it can induce cortisol-driven overactivation of renal mineralocorticoid receptors. Excess mineralocorticoid can manifest as sodium retention, hypokalaemia, low plasma renin and aldosterone concentrations, and hypertension [5]. The pathogenesis of liquorice-induced PRES is thought to be driven by the resultant hypertension. In a
previous case report by Van Beers et al. [7], the authors have also suggested that mineralocorticoid excess can cause endothelial dysfunction independent of blood pressure and it seems likely these two mechanisms are complementary in the pathogenesis of PRES. To our knowledge there have only been three reported cases of PRES associated with liquorice consumption [6– 8]. In our case, previously diagnosed hypertension was well controlled with ACE inhibitor monotherapy as documented on serial recordings by her general practitioner. She presented acutely with a marked elevation in systolic blood pressure, hypokalaemia and a sodium level on the upper limit of normal, a picture consistent with mineralocorticoid excess driven by glycyrrhizic acid. This case highlights the importance of a careful clinical history in identifying and removing potential triggers, which, along with supportive therapy and blood pressure control, is the mainstay of treatment of this condition. Conflict of interest
None.
References 1. Hinchey J, Chaves C, Appignani B et al (1996) A reversible posterior leukoencephalopathy syndrome. N Engl J Med 334:494–500 2. Lee VH, Wijdicks EF, Manno EM, Rabinstein AA (2008) Clinical spectrum of reversible posterior leukoencephalopathy syndrome. Arch Neurol 65(2):205–210 3. Roth C, Ferbert A (2011) The posterior reversible encephalopathy syndrome: what’s certain, what’s new? Pract Neurol 11:136–144 4. Walker BR, Edwards CR (1994) Licorice-induced hypertension and syndromes of apparent mineralocorticoid excess. Endocrinol Metab Clin North Am 23(2):359–377 5. Ferrari P, Lovati E, Frey FJ (2000) The role of the 11betahydroxysteroid dehydrogenase type 2 in human hypertension. J Hypertens 18(3):241–248 6. Chatterjee N, Domoto-Reilly K, Fecci PE, Schwamm LH, Singhal AB (2010) Licorice-associated reversible cerebral vasoconstriction with PRES. Neurology 75(21):1939–1941 7. Van Beers EJ, Stam J, van den Bergh WM (2011) Licorice consumption as a cause of posterior reversible encephalopathy syndrome: a case report. Crit Care 15(1):R64 8. Morgan RD, Chou SH, Stelfox HT (2011) Posterior reversible encephalopathy syndrome in a patient following binge liquorice ingestion. J Neurol 258:1720–1722
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CASE BASED REVIEW
Posterior reversible encephalopathy syndrome (PRES) associated with liquorice consumption K. O’Connell • J. Kinsella • C. McMahon J. Holian • S. O’Riordan
•
Received: 29 May 2014 / Accepted: 14 October 2014 Ó Royal Academy of Medicine in Ireland 2014
Abstract Importance Posterior reversible encephalopathy syndrome (PRES) is a medical emergency but prompt recognition, early institution of supportive care and identifying and removing potential triggers are associated with a good clinical outcome. We report an unusual case of PRES associated with liquorice consumption. Observations A 56-year-old lady presented with thunderclap headache, visual disturbance and a generalised tonic–clonic seizure. Blood pressure on admission was markedly elevated but improved within 24 h. Cranial CT and lumbar puncture were normal (no xanthochromia). She had hypokalaemia. Cranial MRI revealed abnormalities in the occipital lobes consistent with PRES. There was no evidence of restricted diffusion or vasoconstriction. Follow-up MRI 3 weeks later demonstrated complete resolution. On direct questioning she revealed in recent months she had habitually eaten liquorice sweets each day; they were ‘‘on special offer’’ in her local shop. Conclusion and relevance Liquorice contains a biologically active compound glycyrrhizic acid which inhibits 11b hydroxysteroid dehydrogenase. Excessive liquorice consumption can cause mineralocorticoid excess and has been
K. O’Connell (&) J. Kinsella S. O’Riordan Department of Neurology, St Vincent’s University Hospital, Elm Park, Dublin 4, Ireland e-mail: [email protected] C. McMahon Department of Radiology, St Vincent’s University Hospital, Dublin, Ireland J. Holian Department of Nephrology, St Vincent’s University Hospital, Dublin, Ireland
recently reported to cause PRES. We propose that in the absence of other triggers, frequent liquorice consumption precipitated the development of PRES in our patient and should be considered as a possible cause of this condition. Keywords Posterior reversible encephalopathy syndrome Liquorice Hypertension
Case report A 56-year-old woman presented to our hospital with acute onset thunderclap headache predominantly affecting the left fronto-temporal region before extending to involve the occipital regions bilaterally. She rated the pain as ten out of ten in severity. She had associated nausea but no vomiting. She described visual disturbance with zig-zag lines and then more vivid colours predominantly in her right visual field. While in the emergency department she had a generalised tonic–clonic seizure that resolved spontaneously after 60 s. Her only preceding medical history was of benign colonic polyps and mild hypertension for a number of years that was well controlled with low-dose ACE inhibitor. On examination, she was alert but disoriented to place and time in keeping with post-ictal confusion. Blood pressure was elevated at 210/80 mm Hg but this settled within 24 h without additional antihypertensive treatment. There was no clinical evidence of raised intracranial pressure. Visual fields were full and the remainder of the neurological examination was normal. CT brain was normal. CSF contained 4 white cells/cm2, 222 red cells/cm2, protein 0.43 g/L, glucose 4.6 mEq/L (serum 8.9 mEq/L) and there was no xanthochromia. Opening pressure was 160 mm of water. An initial peripheral leucocytosis quickly normalised and ESR and
123
Ir J Med Sci
Fig. 1 Axial FLAIR sequence MRI taken on admission showing hyperintense lesions predominantly affecting the occipital lobes bilaterally, which would be in keeping with PRES
Fig. 2 Axial FLAIR sequence MRI taken 3 weeks after presentation showing resolution of the previously documented changes
CRP were normal. She was hypokalaemic at 3.0 mEq/L (range 3.5–5.0) and sodium was at the upper limit of normal at 145 mEq/L (range 136–145). Electroencephalogram (EEG) was performed approximately 36 h after witnessed seizure and showed evidence of intermittent, 4–7 per second focal sharpened activity involving the left anterior temporal region without electrographic seizures. Cranial MRI (Fig. 1) revealed foci of T2 and FLAIR hyperintensity predominantly in the occipital lobes, consistent with posterior reversible encephalopathy syndrome (PRES). No areas of restricted diffusion were noted.
123
Intracranial MR angiogram showed no evidence of vasoconstriction. Her headache settled during the first 24 h of admission but visual disturbance persisted for 48 h with ongoing blurred vision affecting both eyes and the appearance of letters in her visual field. She was commenced on phenytoin and clobazam and she had no further generalised seizures. Her blood pressure remained within normal limits on her regular dose of ACE inhibitor. Follow-up MRI brain at 3 weeks (Fig. 2) showed complete resolution of the previously documented
Ir J Med Sci
abnormalities. Anticonvulsant treatment was stopped after 2 months and she remains seizure free at 18-month followup. On direct questioning she revealed that in recent months she had habitually eaten liquorice sweets each day as they were ‘‘on special offer’’ in her local shop. In view of the supportive biochemical findings and in the absence of other potential triggers we diagnosed posterior reversible encephalopathy syndrome (PRES) associated with liquorice consumption. The patient was advised to avoid further liquorice consumption.
Discussion Posterior reversible encephalopathy syndrome, originally described by Hinchey and colleagues in 1996 [1], comprises a clinical syndrome of headache, altered mental status, seizures and visual symptoms which can include cortical blindness, blurred vision, visual neglect and visual hallucinations. The pathogenesis is not fully understood but it has been proposed that endothelial damage either as a direct effect of certain medications or due to sudden elevations in blood pressure causes a breakdown of the blood– brain barrier. This gives rise to areas of cerebral oedema and petechial haemorrhages. Imaging studies demonstrate a predominantly posterior leukoencephalopathy. There have been many reported associations or triggers including renal impairment, immunosuppression, chemotherapy and eclampsia [2]. Acute elevation in systemic blood pressure is seen in the majority of cases [1–3] making it a significant aetiological factor. Liquorice contains a biologically active compound, glycyrrhizic acid, which inhibits 11b hydroxysteroid dehydrogenase, the enzyme responsible for the conversion of cortisol to cortisone [4]. When consumed in large quantities, it can induce cortisol-driven overactivation of renal mineralocorticoid receptors. Excess mineralocorticoid can manifest as sodium retention, hypokalaemia, low plasma renin and aldosterone concentrations, and hypertension [5]. The pathogenesis of liquorice-induced PRES is thought to be driven by the resultant hypertension. In a
previous case report by Van Beers et al. [7], the authors have also suggested that mineralocorticoid excess can cause endothelial dysfunction independent of blood pressure and it seems likely these two mechanisms are complementary in the pathogenesis of PRES. To our knowledge there have only been three reported cases of PRES associated with liquorice consumption [6– 8]. In our case, previously diagnosed hypertension was well controlled with ACE inhibitor monotherapy as documented on serial recordings by her general practitioner. She presented acutely with a marked elevation in systolic blood pressure, hypokalaemia and a sodium level on the upper limit of normal, a picture consistent with mineralocorticoid excess driven by glycyrrhizic acid. This case highlights the importance of a careful clinical history in identifying and removing potential triggers, which, along with supportive therapy and blood pressure control, is the mainstay of treatment of this condition. Conflict of interest
None.
References 1. Hinchey J, Chaves C, Appignani B et al (1996) A reversible posterior leukoencephalopathy syndrome. N Engl J Med 334:494–500 2. Lee VH, Wijdicks EF, Manno EM, Rabinstein AA (2008) Clinical spectrum of reversible posterior leukoencephalopathy syndrome. Arch Neurol 65(2):205–210 3. Roth C, Ferbert A (2011) The posterior reversible encephalopathy syndrome: what’s certain, what’s new? Pract Neurol 11:136–144 4. Walker BR, Edwards CR (1994) Licorice-induced hypertension and syndromes of apparent mineralocorticoid excess. Endocrinol Metab Clin North Am 23(2):359–377 5. Ferrari P, Lovati E, Frey FJ (2000) The role of the 11betahydroxysteroid dehydrogenase type 2 in human hypertension. J Hypertens 18(3):241–248 6. Chatterjee N, Domoto-Reilly K, Fecci PE, Schwamm LH, Singhal AB (2010) Licorice-associated reversible cerebral vasoconstriction with PRES. Neurology 75(21):1939–1941 7. Van Beers EJ, Stam J, van den Bergh WM (2011) Licorice consumption as a cause of posterior reversible encephalopathy syndrome: a case report. Crit Care 15(1):R64 8. Morgan RD, Chou SH, Stelfox HT (2011) Posterior reversible encephalopathy syndrome in a patient following binge liquorice ingestion. J Neurol 258:1720–1722
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