|Year : 2019 | Volume
| Issue : 3 | Page : 137-139
Porphyria: An uncommon cause of posterior reversible encephalopathy syndrome
Vinay Agarwal1, Namit Singhal2
1 Chief Neurologist, Agarwal Neurology Clinic, Agra, Uttar Pradesh, India
2 Director neurosciences, S S Hospital, Agra, Uttar Pradesh, India
|Date of Submission||03-Feb-2019|
|Date of Decision||23-Jun-2019|
|Date of Acceptance||22-Jul-2019|
|Date of Web Publication||27-Sep-2019|
Dr. Namit Singhal
Director neurosciences, S S Hospital, Hari Parwat, Agra 282002, Uttar pradesh.
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Acute intermittent porphyria (AIP) is rare and the diagnosis is often delayed. It usually presents with abdominal symptoms, behavioural changes, seizures, tachycardia, and hypertension. MRI findings are usually normal or few contrast enhancing lesions may be present. Rarely , reversible vasogenic edema is seen on MRI as T2 weighted and FLAIR hyper intensity without diffusion restriction suggestive of posterior reversible encephalopathy syndrome (PRES). Review of literature suggests that there are only few case reports of AIP associated with PRES. Because diffusion-weighted MRI is normal, the lesions are likely caused by reversible vasogenic edema and transient breakdown of the blood-brain barrier. Treatment of porphyria consists of a high carbohydrate diet supplemented with the use of intravenous glucose and haematin infusions during acute attacks. Management of seizures with commonly used anti-epileptics including phenytoin, valproic acid, carbamazepine and barbiturates can worsen symptoms or precipitate acute attacks because of their enzyme inducing activity. Levetiracetam is the preferred choice these cases. Porphyria is an important differential diagnosis in patients with unexplained abdominal pain along with neuro-psychiatric manifestations. This case report adds to a handful of cases worldwide associating AIP with radiological findings of PRES.
Keywords: porphyria, seizures, reversible encephalopathy
|How to cite this article:|
Agarwal V, Singhal N. Porphyria: An uncommon cause of posterior reversible encephalopathy syndrome. J Pediatr Neurosci 2019;14:137-9
| Introduction|| |
Acute intermittent porphyria (AIP) is rare and its diagnosis is often delayed. It is an autosomal-dominant disorder resulting from the partial deficiency of porphobilinogen (PBG) deaminase, an enzyme of the heme biosynthesis pathway. Symptoms of AIP include abdominal pain, nausea, vomiting, behavioral changes, seizures, tachycardia, and hypertension. Magnetic resonance imaging (MRI) findings are usually normal or few contrast-enhancing lesions may be present. Rarely, reversible vasogenic edema is seen on MRI as T2-weighted and fluid attenuated inversion recovery (FLAIR) hyperintensity without diffusion restriction, suggestive of posterior reversible encephalopathy syndrome (PRES). Review of literature suggests that there are only few case reports of AIP associated with PRES, which is thought to result from peaks in hypertension.
Although precise mechanism of central nervous system symptoms in AIP is not known, it might be related to deficiency of nitric oxide synthase (NOS). Deficiency of NOS results in decreased production of nitric oxide, which is a major vascular dilator, thereby leading to vasoconstriction. The hypoperfusion associated with vasoconstriction leads to vasogenic edema, which is a characteristic feature of PRES.
The confounding clinical presentation and staggering therapeutic implications give novelty to this case report.
| Case Report|| |
A 16-year-old girl was taken to a local physician with complaints of recurrent abdominal pain and behavioral abnormality for two months. She had a history of two episodes of generalized tonic–clonic convulsions one month back with altered sensorium, which lasted for two days. Computed tomography scan of head was performed, which was normal. She was normotensive at presentation. Investigations revealed normal renal and liver parameters, negative antinuclear antibodies, normal urinalysis, and normal ultrasound abdomen. She was put on antituberculosis drugs for her abdominal complaints and on phenytoin for seizures.
After one month, she presented to us with altered sensorium for the last three days along with severe abdominal pain. On examination, she was found to be confused and disoriented. No focal signs, no meningeal signs, and no abdominal tenderness were observed. Contrast enhanced magnetic resonance imaging brain was performed, which showed T2-weighted and FLAIR hyperintensity in bilateral parieto-occipital lobes [Figure 1] and [Figure 2]. No diffusion restriction was observed on diffusion-weighted images [Figure 3]. These findings were suggestive of PRES. In view of recurrent abdominal pain, behavioral abnormality, and seizures, she was investigated for porphyria. Biochemical evaluation revealed markedly increased levels of urinary Porphobilinogen and aminolevulinic acid. She was given high carbohydrate diet and intravenous (IV) glucose, to which she responded dramatically over the next three days. In view of significant clinical improvement with IV glucose, heme was not given.
|Figure 1: Axial T2-weighted MRI showing hyperintensity in bilateral parietal lobes|
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|Figure 2: Axial FLAIR MRI showing hyperintensity in bilateral parietal lobes|
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|Figure 3: Diffusion-weighted MRI showing absence of any diffusion restriction|
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| Discussion|| |
AIP is characterized by periodic acute attacks of neurovisceral symptoms and may stay occult for a long time. The acute attacks are characterized by abdominal pain, neurologic deficits, psychiatric symptoms, and colored urine. MRI of AIP shows multiple large, contrast-enhancing, subcortical white matter lesions, which regress with glucose and hematin infusions. Diffusion-weighted MRI is normal., MRI findings of AIP can differ from those in PRES by virtue of intense contrast enhancement. Because diffusion-weighted MRI is normal, the lesions are likely caused by reversible vasogenic edema and transient breakdown of the blood–brain barrier.
Although the precise mechanism underlying such findings remains unknown, there are several hypotheses. Hypertension during an acute attack of AIP might exceed the autoregulation limit, leading to breakdown of the blood–brain barrier and subsequent vasogenic edema., However, our patient remained normotensive throughout, thereby suggesting that other mechanisms are also involved. Severe heme deficiency during an acute attack of AIP causes a lack of the heme protein NOS. Subsequently, vasodilator effect of NOS-derived nitric oxide is lost, which is crucial for maintaining the cerebral blood flow, leading to vasoconstriction. Alternatively, excessive porphyrin precursors might cause direct endothelial cell damage followed by a breakdown of the blood–brain barrier and release of potent vasoconstrictors such as endothelin or thromboxane.,
Treatment of porphyria consists of a high carbohydrate diet supplemented with the use of IV glucose and hematin infusions during acute attacks. They suppress 5-aminolevulinic acid synthase and the accumulation of heme precursors. Management of seizures can actually worsen the condition. Many commonly used antiepileptics, including phenytoin, valproic acid, carbamazepine, and barbiturates, worsen symptoms or precipitate acute attacks because of their enzyme-inducing activity. Levetiracetam is the preferred choice should seizure medication be required. This was probably the reason for acute deterioration in our patient, related to use of phenytoin and antituberculosis drugs.
Porphyria is an important differential diagnosis in patients with unexplained abdominal pain along with neuropsychiatric manifestations. This case report adds to a handful of cases worldwide, associating AIP with radiological findings of PRES.
| Learning Points|| |
This case report is not that common. It adds to a handful of cases worldwide associating AIP with radiological findings of PRES.
Combination of abdominal pain with neuropsychiatric symptoms should always prompt for consideration of porphyria. The case report highlights the fact that AIP can be easily confused with tuberculosis, which is endemic in India, unless a high index of suspicion is kept in mind.
Also, institution of Anti tubercular therapy can further lead to neurological deterioration; rifampicin being an enzyme inducer.
Rarely, PRES can be a manifestation of porphyria without hypertension.
Inadvertent use of enzyme-inducing drugs should be avoided to prevent aggravation of disease.
Levetiracetam is the antiepileptic drug of choice in porphyria.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]