pathy; nephrotic syndrome; tibolone. 190/100 mmHg and she had marked facial and limb oedema with bilateral pleural effusions. Her visual acuity was reduced ...
Nephrol Dial Transplant (1999) 14: 1750–1752
Nephrology Dialysis Transplantation
Case Report
Hypertensive encephalopathy and nephrotic syndrome: a possible link? Ewan R. Pearson, Richard J. D’Souza, 1Clive Hamilton-Wood, Anthony J. Nicholls and Martin Beaman Renal Unit and 1Department of Radiology, Royal Devon and Exeter Hospital, Exeter, Devon, UK
Key words: cortical blindness; hypertensive encephalopathy; nephrotic syndrome; tibolone
Introduction Hypertensive encephalopathy is an acute hypertensive syndrome characterized by seizures, decreased conscious level and sensory disturbance [1,2]. We present a case of a patient who developed hypertensive encephalopathy in association with nephrotic syndrome, and discuss possible factors linking the two conditions.
Case A 55-year-old woman presented with a witnessed grand mal seizure after 2 days of severe occipital headache, nausea, vomiting and photophobia. She had suffered from migraine for many years but took no regular therapy. She had, however, been taking tibolone for menopausal flushing. There was no other medical history. Her temperature was 38.4°C, pulse 90/min, blood pressure 170/70 mmHg. There was marked neck stiffness, but there was no focal abnormality on cranial or peripheral nerve examination. Examination was otherwise normal. Meningitis initially was diagnosed, and treatment with cefotaxime and benzylpenicillin was commenced. A CT scan of the brain showed no focal abnormality, space-occupying lesion or haemorrhage. CSF examination was unremarkable (total white cell count 2×106/l; total red cell count 68×106/l; protein 200 mg/l; serum glucose 6.5 mmol/l; glucose 4.6 mmol/l; no organisms seen or cultured). Antibiotics were stopped, and i.v. aciclovir was commenced on suspicion of herpes simplex encephalitis. She deteriorated over the next 2 days, becoming increasingly drowsy, complaining of blurred vision and Correspondence and offprint requests to: Dr. R. J. D’Souza, Renal Unit, Royal Devon and Exeter Hospital, Barrack Road, Exeter EX2 5DW, UK.
developing periorbital oedema. Her blood pressure was 190/100 mmHg and she had marked facial and limb oedema with bilateral pleural effusions. Her visual acuity was reduced to 6/60 in both eyes. A horizontal diplopia was present in all positions of gaze. A slit lamp examination of the fundi was normal, with no intra-ocular cause for her decreased visual acuity found, suggesting an occipital cortex lesion. Urinalysis showed >3 g/l proteinuria, and a subsequent 24 h urinary protein was recorded at 44.4 g. Laboratory investigations were as follows: haemoglobin 13.8 g/dl, white cell count 11.3×109/l, platelet count 212×109/l, serum sodium 143 mmol/l, potassium 3.5 mmol/l, serum creatinine 117 mmol/l, urea 11.2 mmol/l, corrected calcium 2.14 mmol/l, phosphate 0.91 mmol/l, albumin 32 g/l, total protein 55 g/l, C-reactive protein 15 mg/l, erythrocyte sedimentation rate 11 mm/h, triglycerides 2.07 mmol/l and cholesterol 6.5 mmol/l. The creatinine clearance was 100 ml/min. Immunological tests (ANCA, auto-immune profile, anti-dsDNA, ASO titre) were all negative. The immunoglobulin levels were as follows: IgA 0.55 g/l, IgG 4.3 g/l, IgM 2.14 g/l. Serum protein electrophoresis showed an increased a2 band. Cryoglobulins were not detected. A T -weighted cranial MRI showed increased signal 2 intensity in the occipital lobes bilaterally, consistent with vasogenic oedema (see Figure 1). Magnetic resonance venography showed no abnormality in the sagittal sinus. These features were felt to be consistent with hypertensive encephalopathy. She was given nifedipine L.A, doxazosin and frusemide. The tibolone was stopped. She had further grand mal seizures, and was commenced on phenytoin. A good diuresis was achieved and the blood pressure decreased to 140/70 mmHg. Renal biopsy showed mesangial proliferative glomerulonephritis. Immunoflorescence was negative and electron microscopy was normal. She clinically improved with reduction of the blood pressure and diuresis. Her visual acuity returned to normal over the next 4 days, the seizures ceased and her headache and drowsiness resolved. In view of the heavy proteinuria, a trial of immunosuppression was commenced with prednisolone 60 mg and azathioprine
© 1999 European Renal Association–European Dialysis and Transplant Association
Hypertensive encephalopathy in association with nephrotic syndrome
Fig. 1. Parasagittal T -weighted MRI of the brain showing a mark2 edly increased signal in the occipital white matter, consistent with vasogenic oedema.
150 mg daily. The 24 h urinary protein loss decreased to 0.56 g by 2 months, and her renal function remained normal.
Discussion The combination of neurological symptoms, particularly cortical blindness, with hypertension and the MRI findings of bilateral occipital oedema are strongly suggestive of hypertensive encephalopathy [3,4]. One generally accepted explanation for the pathogenesis of hypertensive encephalopathy is that there is loss of cerebral autoregulation of blood pressure leading to endothelial damage and subsequent extravasation of fluid [2,5]. Cerebral blood flow autoregulation usually operates between a mean blood pressure of 60 and 150 mmHg [6 ]. However, in this case and in other reported cases [4], the blood pressure has not been raised above this theoretical upper limit and it may be that other factors are involved in the pathogenesis of hypertensive encephalopathy. Our patient had two potential precipitating factors. Firstly, she had nephrotic syndrome and secondly she was taking the synthetic steroid tibolone. Two cases of nephrotic syndrome associated with hypertensive encephalopathy have been reported: a 4-year-old child with minimal change nephrotic syndrome, hypertension, focal seizures and cortical blindness whose CT scan showed occipital white matter lucencies [7]; and a 61-year-old nephrotic woman with hypertension, cortical blindness, seizures and MRI changes consistent with hypertensive encephalopathy [4]. Our case is similar to the latter, but initial symptoms were of headache, nausea and vomiting with the development of oedema 48 h after admission. If fluid extravasation from intracerebral capillaries due to failure of autoregulation of cerebral blood perfusion plays a role in the pathogenesis of hypertens-
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ive encephalopathy, it may be that the reduced plasma oncotic pressure due to the heavy urinary protein loss makes fluid extravasation more likely at lower blood pressures, hence increasing the risk of developing hypertensive encephalopathy in these patients. It has also been suggested that the pathology of nephrotic syndrome is not restricted simply to increased permeability of the glomerular basement membrane, but may be a more generalized condition due to widespread increase in permeability of capillaries [8]. Therefore in nephrotic syndrome, fluid extravasation from cerebral capillaries may be more likely than in non-nephrotic patients, which would contribute to the development of hypertensive encephalopathy. The use of human albumin solution in the management of nephrotic syndrome may be detrimental to outcome [9]. Prior to transfer to our renal unit, this patient was treated with i.v. fluids before the diagnosis of nephrotic syndrome was realized, and then with albumin solution on diagnosis. It has been suggested that fluid overload may be a risk factor for developing hypertensive encephalopathy [4], and it is likely, therefore, that the use of albumin solution and i.v. fluids may have precipitated/worsened the hypertensive encephalopathy. Hypertensive encephalopathy, eclampsia and the cerebral side effects of immunosuppressive agents cause similar clinical features and typical brain MRI/CT scan findings of parieto-occipital oedema. These conditions have been grouped together as ‘a posterior leukoencephalopathy syndrome’ [4]. Our patient was taking tibolone, a synthetic steroid with weak oestrogenic, androgenic and progestagenic properties used for relief of post-menopausal flushing. By altering the hormonal environment, it may affect cerebral haemodynamics and endothelial function in a similar way to that hypothesized for eclampsia [10]. Since tibolone has also been associated with hypertension [Organon Laboratories Ltd, personal communication], it may have contributed to the development of hypertensive encephalopathy in our patient. Renal disease, pregnancy or the use of immunosuppressive agents [4] predispose to the development of a hypertensive encephalopathy syndrome. The diagnosis should be considered even without other features of accelerated hypertension if other risk factors such as renal disease are present. An early cranial MR scan should be performed and antihypertensive treatment commenced.
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1752 leukoencephalopathy syndrome. N Engl J Med 1996; 334: 494–500 5. Johansson B. The blood–brain barrier and cerebral blood flow in acute hypertension. Acta Med Scand 1983; 678 [Suppl ]: 107–112 6. Paulson OB, Strandgaard S, Evinson L. Cerebral autoregulation. Cerebrovasc Brain Metab Rev 1990; 2: 161–192 7. Assadi FK, Lansky LL, John EG, et al. Acute hypertensive encephalopathy in minimal change nephrotic syndrome. Child Nephrol Urol 1990; 10: 96–99
E. R. Pearson et al. 8. Lewis DM, Tooke JE, Beaman M et al. Peripheral microvascular parameters in the nephrotic syndrome. Kidney Int 1998; 54: 1261–1266 9. Dorhout Mees EJ. Does it make sense to administer albumin to the patient with nephrotic oedema? Nephrol Dial Transplant 1996; 11: 1224–1226 10. Zunker P, Ley-Pozo J, Louwen F et al. Cerebral haemodynamics in pre-eclampsia/eclampsia syndrome. Ultrasound Obstet Gynaecol 1995; 6: 411–415
Received for publication: 5.2.99 Accepted: 26.2.99
