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Table of Contents    
Year : 2015  |  Volume : 63  |  Issue : 4  |  Page : 607-609

Posterior reversible encephalopathy syndrome as a rare presenting feature of acute intermittent porphyria

1 Department of Medicine, Dr. S.N. Medical College, Jodhpur Satyam MRI, Jodhpur, Rajasthan, India
2 Department of Radiodiagnosis, Dr. S.N. Medical College, Jodhpur, Rajasthan, India

Date of Web Publication4-Aug-2015

Correspondence Address:
Hans Raj Pahadiya
Department of Medicine, Dr. S.N. Medical College, Jodhpur Satyam MRI, Jodhpur, Rajasthan
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0028-3886.162081

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How to cite this article:
Lakhotia M, Pahadiya HR, Singh J, Bhansali S, Choudhary S, Jangid H. Posterior reversible encephalopathy syndrome as a rare presenting feature of acute intermittent porphyria. Neurol India 2015;63:607-9

How to cite this URL:
Lakhotia M, Pahadiya HR, Singh J, Bhansali S, Choudhary S, Jangid H. Posterior reversible encephalopathy syndrome as a rare presenting feature of acute intermittent porphyria. Neurol India [serial online] 2015 [cited 2023 Dec 8];63:607-9. Available from:


Acute intermittent porphyria (AIP) can affect the autonomic, peripheral and central nervous system (CNS). Posterior reversible encephalopathy syndrome (PRES) is a rare clinico-neuro-radiological entity and a rare presenting feature of AIP. We describe a 25-year-old lady, who presented with PRES and was diagnosed to be having AIP.

A 25-year-old non-alcoholic, non-pregnant lady was admitted to our hospital because of the history of occipital headache, vision loss in both eyes and two episodes of generalised tonic-clonic seizures. She also had compliants of colicky abdominal pain, constipation and vomiting for 15 days for which she was admitted in different local hospitals 2 times without any confirmed diagnosis. Her father gave a history of similar episodes of abdominal pain since the last one year. Pain occurred once in 2 months and remained for 10-15 days. There was no family history of porphyria. There was no history of trauma in the recent past nor of drug addiction. At the time of admission, she was in a confused state, drowsy, disorientated, psychotic and agitated. A loading dose of intravenous phenytoin was administered as prophylaxis for seizures. After 4 h, she regained consciousness and became well oriented, cooperating well while undergoing her neurological examination. However, she was still complaining of headache and vision loss. On examination, her fundoscopy was normal. There were no sensory and motor deficits. Her plantars were bilateral flexors. The abdomen was soft, non-tender with no organomegaly. The blood pressure was 178/100 mmHg, pulse rate 118/min and regular, respiratory rate 18 breaths/min and temperature was 37.1°C at axilla. The respiratory system examination was within normal limits.

Laboratory investigations revealed a haemoglobin of 10.3 g/dL, a total leucocyte count of 9430/mm 3 with normal differential counts and a platelet count of 304,000/mm 3 . The blood sugar was 90 mg/dL, blood urea 51 mg/dL, serum creatinine 1.03 mg/dL, aspartate transaminase 45 IU/L, alanine transaminase 75 IU/L, serum lactate dehydrogenase 474 IU/L and total protein 6.2 g/dL with 3.92 g/dL albumin. The serum amylase was 90 U/L (reference value 27-137 U/L), and lipase 131U/L (reference value <190 U/L). The electrolytes values were serum sodium 129 meq/L, serum potassium 3.04 meq/L, serum calcium 8.9 mg/dL and serum phosphorus 4.6 mg/dL. The thyroid profile and cerebrospinal fluid examination were normal. The patient was sero-negative for HIV, hepatitis B virus and hepatitis C virus and antinuclear antibody was negative. Her urine turned dark red on exposure to light. Porphyrins were detected on urine spot examination. A 24 h urinary 5-aminolevulinic acid (ALA) was 7.8 mg/L and porphyrinobilinogen was 10.5 mg/L. Her chest X-ray postero-anterior view, ultrasonography of abdomen and pelvis, electrocardiogram and two-dimensional echocardiography were within normal limits. Magnetic resonance imaging (MRI) of the brain showed bilateral cortical and subcortical altered signal intensities involving the parieto-occipital areas. They were hypointense on T1-weighted images, hyperintense on T2-weighted and fluid-attenuated inversion recovery images with no diffusion restriction, which was suggestive of PRES. The MR venogram study was normal [Figure 1]a-c. The clinical and laboratory findings were suggestive of AIP. She was treated with antiepileptic levetiracetam, antihypertensive b-blockers and labetalol, along with supportive measures. The glucose infusion was started at the dose of 400 g/day and she got relieved of her symptoms.
Figure 1: (a) Magnetic resonance imaging (MRI) brain axial section fluid - attenuated inversion recovery image showing bilateral parietooccipital hyperintense signals; (b) MRI brain coronal section showing bilateral hyperintense signals in parietotemporal region; (c) MR venogarm showed a normal study

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Acute intermittent porphyria (AIP) is an inherited metabolic disorder of heme synthesis with an autosomal dominant pattern of inheritance. The disease is common in middle-aged female patients and is caused by a partial deficiency of porphobilinogen deaminase in heme biosynthesis. AIP is characterised by the urinary excretion of abnormal quantities of uroporphyrin, coproporphyrin and porphobilinogen. The common presenting symptoms are intermittent attacks of acute abdominal pain, constipation, tachycardia, hypertension and neuro-psychiatric symptoms, most of which are related to autonomic dysfunction. [1] The triggers for the precipitating symptoms of AIP are porphyrinogenic drugs, alcohol, infections, calorie-restricted diet, stress and hormonal influences (pregnancy and menstrual cycle). [1],[2]

The neurological manifestations of AIP are polymorphic. It can affect the central, peripheral and autonomic nervous system. The incidence of neurological manifestations in symptomatic patients is very low being approximately 5-17%. [3] Acute onset of neurological symptoms in an undiagnosed case of AIP is associated with poor prognosis with a high mortality (10%). [4] The neurological manifestations of AIP are acute peripheral neuropathy and acute encephalopathy. The peripheral neuropathy is the most common neurological presentation of an acute attack of AIP and is predominantly axonal motor neuropathy. Acute encephalopathy manifests as a combination of varied symptoms. It includes mild mental symptoms, headache, seizures, syndrome of inappropriate anti diuretic hormone, PRES, altered sensorium and rarely focal CNS deficits. Altered mental status ranges from mild symptoms such as anxiety, insomnia and depression to severe symptoms of hallucination and delusion. [5]

The cause of neuropsychiatric manifestations in AIP is not well understood. The mechanism of neuronal damage is complex. Over production of porphyrin precursor, amino laevulinic acid (ALA) from the liver in the circulation and critical deficiency of heme and heme protein in the liver or/and in neuronal tissue is responsible for the disruption of blood brain barrier and blood-nerve barrier. ALA is a direct neurotoxin and leads to the formation of free radical and reactive oxygen species. It also inhibits Na-K-ATPase and modifies glutamatergic release, which may initiate the neuronal damage. [5] The explanation for the altered mental status in acute attack is the high affinity of ALA even in very low concentrations to gamma-aminobutyric acid and glutamate receptors (because of their structural similarity) in the presence of disrupted blood brain barrier in the limbic area. [6]

Autonomic neuropathy in AIP is responsible for the majority of symptoms including pain abdomen, tachycardia, hypertension and constipation. The mechanism of pain abdomen is explained by autonomic dysfunction, enteric ganglionitis/ganglionopathy, [7] local vasoconstriction and intestinal ischaemia. Vagal nerve demyelination, axonal loss and chromatolysis of sympathetic ganglion cells in autopsies support the direct involvement of autonomic fibres. [8] Acute pan-dysautonomia in AIP leads to autonomic neuropathy with a predominance of parasympathetic insufficiency. [9]

Posterior reversible encephalopathy syndrome has been found in the patients of AIP as a symptom of acute encephalopathy in the acute severe attack. [10],[11] PRES has distinct clinical and neuroimaging features and is characterised by the sudden onset of headache, seizures, altered mental status and visual disturbances. PRES is most commonly associated with acute hypertension, preeclampsia/eclampsia and immunosuppressive agents. MRI studies typically show oedema involving bilateral white matter of posterior cerebral, regions, especially the parieto-occipital lobes, and sometimes the frontal and temporal lobes. Other encephalic structures may also be involved. [12]

During an acute attack of AIP, the blood pressure increases. Hypertension acts more like a co-factor for PRES. The blood-brain barrier is disrupted in PRES and also in AIP. The permeability is increased which permits access of neurotoxins such as ALA to the neurons. Therefore, endothelial toxicity is considered as the main cause of vasogenic oedema in AIP. [13] Our patient presented with a history of headache, seizures and visual disturbances with a recorded high blood pressure. MRI findings were suggestive of PRES. The clinico-laboratory profile was consistent with a diagnosis of AIP. We presume that blood pressure was increased because of dysautonomic activity of the underlying AIP. Finally, we conclude that in the evaluation of patients with PRES, the clinician should keep the possibility of AIP as the underlying cause.

 » References Top

Anderson KE, Bloomer JR, Bonkovsky HL, Kushner JP, Pierach CA, Pimstone NR, et al. Recommendations for the diagnosis and treatment of the acute porphyrias. Ann Intern Med 2005;142:439-50.  Back to cited text no. 1
McColl KE, Dover S, Fitzsimons E, Moore MR. Porphyrin metabolisms and the porphyrias. In: Weatherall DJ, Ledingham JG, Warrell DA, editors. Oxford Textbook of Medicine. 3 rd ed. Oxford: Oxford University Press; 1996. p. 1388-99.  Back to cited text no. 2
Mustajoki P, Nordmann Y. Early administration of heme arginate for acute porphyric attacks. Arch Intern Med 1993;153:2004-8.  Back to cited text no. 3
Pischik E, Bulyanitsa A, Kazakov V, Kauppinen R. Clinical features predictive of a poor prognosis in acute porphyria. J Neurol 2004;251:1538-41.  Back to cited text no. 4
Pischik E, Kauppinen R. Neurological manifestations of acute intermittent porphyria. Cell Mol Biol (Noisy-le-grand) 2009;55:72-83.  Back to cited text no. 5
Brennan MJ, Cantrill RC. Delta-Aminolaevulinic acid and amino acid neurotransmitters. Mol Cell Biochem 1981;38:49-58.  Back to cited text no. 6
Grundy D, Schemann M. Enteric nervous system. Curr Opin Gastroenterol 2006;22:102-10.  Back to cited text no. 7
Suarez JI, Cohen ML, Larkin J, Kernich CA, Hricik DE, Daroff RB. Acute intermittent porphyria: Clinicopathologic correlation. Report of a case and review of the literature. Neurology 1997;48:1678-83.  Back to cited text no. 8
Laiwah AC, Macphee GJ, Boyle P, Moore MR, Goldberg A. Autonomic neuropathy in acute intermittent porphyria. J Neurol Neurosurg Psychiatry 1985;48:1025-30.  Back to cited text no. 9
Celik M, Forta H, Dalkiliç T, Babacan G. MRI reveals reversible lesions resembling posterior reversible encephalopathy in porphyria. Neuroradiology 2002;44:839-41.  Back to cited text no. 10
Zhao B, Wei Q, Wang Y, Chen Y, Shang H. Posterior reversible encephalopathy syndrome in acute intermittent porphyria. Pediatr Neurol 2014;51:457-60.  Back to cited text no. 11
Hinchey J, Chaves C, Appignani B, Breen J, Pao L, Wang A, et al. A reversible posterior leukoencephalopathy syndrome. N Engl J Med 1996;334:494-500.  Back to cited text no. 12
Neal CR, Hunter AJ, Harper SJ, Soothill PW, Bates DO. Plasma from women with severe pre-eclampsia increases microvascular permeability in an animal model in vivo. Clin Sci (Lond) 2004;107:399-405.  Back to cited text no. 13


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