The Neuroradiology Journal 21: 655-659, 2008
www. centauro. it
Reversible MRI Findings of Porphyric Encephalopathy A Report of Two Cases A. SOYSAL, P. DOGAN, C. DAYAN, B.G. CALISKAN, B. ARPACI Bakirkoy Research and Training Hospital for Psychiatry, Neurology and Neurosurgery; Istanbul, Turkey
Key words: porphyria, porphyric encephalopathy, MRI
SUMMARY – We describe the magnetic resonance imaging (MRI) findings in two patients admitted to our institution with neuropsychiatric symptoms and severe abdominal pain diagnosed as acute intermittent porphyria (AIP). MRI revealed multiple lesions which regressed following treatment. We suggest reversible cerebral vasospasm underlies the MRI abnormalities and the cerebral symptoms in porphyria.
Introduction The porphyrias are rare multisystem inherited diseases of heme biosynthesis which can involve the autonomic, peripheral and central nervous system (CNS) 1-4. There are few reports in the literature on MRI findings of porphyria cases with CNS involvement. Those studies suggested that MRI changes are related to reversible ischemic vasculopathy 5-10. We describe two porphyric encephalopathy cases with reversible cerebral lesions on MRI . Case Reports Case 1
In February 1995, a 22-year-old woman with no family history of porphyria had an appendectomy operation due to diffuse abdominal pain. On the first postoperative day she became confused and experienced visual hallucinations. Five days later, she suffered a generalized seizure and was referred to our institution with the diagnosis of status epilepticus. At the time of admission, she was confused, disoriented to time, place and person, and hallucinated. There was no evidence of meningism or fo-
cal neurological deficits. Blood tests were unremarkable. Cranial computed tomography (CT) showed right frontal and bilateral parieto-occipital hypodense lesions without contrast enhancement (figure 1A). Cranial MRI demonstrated diffuse hyperintense gyriform lesions on the T2-weighted and proton density images and hypo or isointense lesions on the T1-weighted images at the same localizations (figure 1B-D). Although the results of cerebrospinal fluid (CSF) analysis including viral antibody were normal, the MRI lesions were thought to be consistent with septic vasculitis or infectious diseases and wide spectrum antibiotics were started. Electroencephalography (EEG) showed bioelectrical disorganization in both temporal regions. On the fourth day she developed quadriparesia and areflexia. Electromyography (EMG) revealed polyneuropathy with severe axonal degeneration affecting motor fibers. Hypertension and tachycardia attacks, urine retention and constipation were determined during her follow-up. At this point, with the combination of central, peripheral and autonomic nervous system findings, acute porphric attack was considered. Urine sample was examined and high urinary porphyrin profiles confirmed the diagnosis of porphyria. Following that, antibiotic 655
Reversible MRI Findings of Porphyric Encephalopathy
A. Soysal
A
B
C
D
E
F
Figure 1 A) Axial CT. B) Axial T2-weighted. C,D) Axial proton density images show right frontal and bilateral parieto-occipital lesions. E,F) Two months later these images show a resolution of these lesions.
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www. centauro. it
The Neuroradiology Journal 21: 655-659, 2008
A
B
C
D
Figure 2 A) Axial and B) coronal FLAIR images show hyperintense gyriform lesions on bilateral frontal, parietal and temporal regions C) Significant regression of lesions after two months. D) After six months.
treatment was stopped, carbohydrate loading, EDTA infusion and physiotherapy were started. Two months later, when she had partially recovered, repeated MRI showed regression of right frontal and both parietal lesions (figure 1E,F). Six months later, she was able to walk with assistance and one year later she recovered completely and seizures were well controlled.
Case 2
In December 2006, a 22-year-old woman with no family history of porphyria was admitted to the emergency room with confusion, disorientation and agitation. The patient had a medical history of appendectomy one week earlier. There was no focal neurological deficit. Her blood pressure was borderline high at some 657
Reversible MRI Findings of Porphyric Encephalopathy
measurements. Blood tests showed only a mild hyponatremia. MRI of the brain demonstrated hyperintense gyriform lesions on the T2weighted and FLAIR images (figure 2A,B) and hypo and isointense lesions on the T1-weighted images on bilateral frontal, parietal and right occipital and temporal regions. The differential diagnosis included encephalitis, CNS vasculitis, and acute disseminated encephalomyelitis. EEG showed generalized disorganization on both hemispheres. CSF analysis showed 15 mm3 lymphocytes, high protein (82 mg/dl) and normal glucose levels. Since the incidence of tuberculosis is high in our country, chemotherapy was started for the probable diagnosis of tuberculous meningoencephalitis. The next day, her neurological examination returned to normal. On the third day, she suffered severe diffuse abdominal pain which did not respond to analgesics. Abdominal examination, ultrasonography and gastroscopy were normal. Abdominal pain was followed by nausea, vomiting, loss of appetite, and constipation. Porphyria was considered in the differential diagnosis due to the existence of the neuropsychiatric symptoms, abdominal pain and dysautonomia. A urine sample was examined and high urinary porphyrin profiles confirmed the diagnosis of porphyria. Chemotherapy for tuberculosis was stopped and she was treated with carbohydrate loading. Her abdominal pain regressed in a few days and did not recur. The cranial MRI performed two and six months later revealed that the lesions determined on first MRI were significantly regressed (figure 2C,D, respectively). Discussion Porphyrias are seven different diseases that are caused by hereditary or acquired defects of heme biosynthesis in which CNS involvement can lead to porphyric encephalopathy. Clinical manifestations of CNS involvement are epileptic seizures, impaired consciousness, behavior changes (anxiety, agitation, confusion, hallucinations etc.) and hyponatremia caused by inappropriate antidiuretic hormone syndrome. Eventually, somnolence and coma may result. Patients also suffer severe abdominal pain, nausea, constipation, labile hypertension and sensorimotor neuropathy caused by autonomic and peripheral nervous system involvement 1-4. There are only a few reported neuropsychiatric porphyria cases in which cranial MRI 658
A. Soysal
abnormalities are shown 5-10. Firstly, King and Bragdon reported transient cranial MRI abnormalities determined during an acute episode of porphyria with neurological symptoms and suggested vasospasm as the cause of these 5. Aggarwal et Al showed transient changes in the cerebral cortex on MRI that resolved on follow-up imaging correlated with the resolution of neurological symptoms and considered that cerebral changes were due to an ischemic vasculopathy 6. Black et Al reported transient cerebral vasospasm demonstrated by both MR angiography and conventional angiography in a case with neurological symptoms of acute porphyria attack and proposed transient vasoreactive ischemia as the cause of cerebral symptoms in porphyric encephalopathy 7. Utz et Al demonstrated reversible cranial MRI lesions in a case with AIP and attributed these lesions and clinical abnormalities to a vascular origin associated with hypertensive encephalopathy 8. Similarly, Celik et Al reported transient MRI findings in a woman with eclampsia in the 38th week of pregnancy diagnosed as AIP and suggested a similar mechanism to posterior reversible encephalopathy syndrome (PRES) underlying cerebral symptoms in porphyria 9. Maramattom et Al demonstrated reversible MRI lesions correlated with the vasospasm demonstrated by cerebral angiography in a case with AIP. They considered the reversible MRI lesions denote a vasogenic edema with temporary breakdown of the blood-brain barrier, possibly induced by heme biosynthetic pathway intermediates and different from lesions of PRES by their contrast enhancement 10 . The MRI findings of our two AIP patients demonstrated reversible multifocal, cortical, diffuse hyperintense lesions and are consistent with earlier reports 5-10. We suggest that these findings are related to reversible ischemic vasculopathy as documented with cerebral angiography in two reports 7-10. The exact mechanism of reversible ischemic vasculopathy is not clear. It is proposed that during acute episodes, a decrease in cerebral nitric oxide (NO) which is synthesized by a flavo-hemoprotein can induce cerebral vasoconstriction since NO is a potent vasodilator 1,2,8. The other proposed mechanisms for the MRI abnormalities include neurotoxicity of porphyrin precursors, aminolevulinic acid, free radicals and deficiency of heme proteins 1,2,4,6,9,10. Neuropsychiatric porphyria with cranial MRI abnormalities is rare and few cases have been reported. We diagnosed only two cases in the
www. centauro. it
last eleven years in our clinic. In conclusion, we emphasize that since the porhyria can be fatal, it should be considered when there are
The Neuroradiology Journal 21: 655-659, 2008
neuropsychiatric symptoms associated with abdominal pain to prevent misdiagnosis, inappropriate treatment and surgical interventions.
References 1 Suarez JI, Cohen ML, Larkin J et Al: Acute intermittent porphyria: Clinicopathologic correlation. Neurology 48: 1678-1683, 1997. 2 Meyer UA, Schuurmans MM, Lındberg RP: Acute porphyrias: pathogenesis of neurological manifestations. Semin Liver Dis 18: 43-52, 1998. 3 Gonzalez-Arriaza HL, Bostwick JM: Acute porphyrias: a case report and review. Am J Psychiatry 160: 450459, 2003. 4 Kauppinen R: Porphyrias. Lancet 365: 241-252, 2005. 5 King PH, Bragdon AC: MRI reveals multiple reversible cerebral lesions in an attack of acute intermittent porphyria. Neurology 41: 1300-1302, 1991. 6 Aggarwal A, Quint DJ, Lynch JP: MR imaging of porphyric encephalopathy. Am J Roentgenol 162: 12181220, 1994. 7 Black KS, Mirsky P, Kalina P et Al: Angiographic demostration of reversible cerebral vasospasm in porphyric encephalopathy. Am J Neuroradiol 16: 1650-1652, 1995. 8 Utz N, Kinkel B, Hedde JP et Al: MR imaging of acute intermittent porphyria mimicking reversible posterior leukoencephalopathy syndrome. Neuroradiology 43: 1059-1062, 2001.
9 Çelik M, Forta H, Dalkılıç T et Al: MRI reveals reversible lesions resembling posterior reversible encephalopathy in porphyria. Neuroradiology 44: 839-841, 2002. 10 Maramattom BV, Zaldivar RA, Glynn SM et Al: Acute intermittent porphyria presenting as a diffuse encephalopathy. Ann Neurol 57: 581-584, 2005.
Aysun Soysal, MD Neurology Department Bakirkoy Research and Training Hospital for Psychiatry Neurology and Neurosurgery Zuhuratbaba Mah. Bakirkoy 34740 Istanbul, Turkey E-mail: [email protected]
659
www. centauro. it
Reversible MRI Findings of Porphyric Encephalopathy A Report of Two Cases A. SOYSAL, P. DOGAN, C. DAYAN, B.G. CALISKAN, B. ARPACI Bakirkoy Research and Training Hospital for Psychiatry, Neurology and Neurosurgery; Istanbul, Turkey
Key words: porphyria, porphyric encephalopathy, MRI
SUMMARY – We describe the magnetic resonance imaging (MRI) findings in two patients admitted to our institution with neuropsychiatric symptoms and severe abdominal pain diagnosed as acute intermittent porphyria (AIP). MRI revealed multiple lesions which regressed following treatment. We suggest reversible cerebral vasospasm underlies the MRI abnormalities and the cerebral symptoms in porphyria.
Introduction The porphyrias are rare multisystem inherited diseases of heme biosynthesis which can involve the autonomic, peripheral and central nervous system (CNS) 1-4. There are few reports in the literature on MRI findings of porphyria cases with CNS involvement. Those studies suggested that MRI changes are related to reversible ischemic vasculopathy 5-10. We describe two porphyric encephalopathy cases with reversible cerebral lesions on MRI . Case Reports Case 1
In February 1995, a 22-year-old woman with no family history of porphyria had an appendectomy operation due to diffuse abdominal pain. On the first postoperative day she became confused and experienced visual hallucinations. Five days later, she suffered a generalized seizure and was referred to our institution with the diagnosis of status epilepticus. At the time of admission, she was confused, disoriented to time, place and person, and hallucinated. There was no evidence of meningism or fo-
cal neurological deficits. Blood tests were unremarkable. Cranial computed tomography (CT) showed right frontal and bilateral parieto-occipital hypodense lesions without contrast enhancement (figure 1A). Cranial MRI demonstrated diffuse hyperintense gyriform lesions on the T2-weighted and proton density images and hypo or isointense lesions on the T1-weighted images at the same localizations (figure 1B-D). Although the results of cerebrospinal fluid (CSF) analysis including viral antibody were normal, the MRI lesions were thought to be consistent with septic vasculitis or infectious diseases and wide spectrum antibiotics were started. Electroencephalography (EEG) showed bioelectrical disorganization in both temporal regions. On the fourth day she developed quadriparesia and areflexia. Electromyography (EMG) revealed polyneuropathy with severe axonal degeneration affecting motor fibers. Hypertension and tachycardia attacks, urine retention and constipation were determined during her follow-up. At this point, with the combination of central, peripheral and autonomic nervous system findings, acute porphric attack was considered. Urine sample was examined and high urinary porphyrin profiles confirmed the diagnosis of porphyria. Following that, antibiotic 655
Reversible MRI Findings of Porphyric Encephalopathy
A. Soysal
A
B
C
D
E
F
Figure 1 A) Axial CT. B) Axial T2-weighted. C,D) Axial proton density images show right frontal and bilateral parieto-occipital lesions. E,F) Two months later these images show a resolution of these lesions.
656
www. centauro. it
The Neuroradiology Journal 21: 655-659, 2008
A
B
C
D
Figure 2 A) Axial and B) coronal FLAIR images show hyperintense gyriform lesions on bilateral frontal, parietal and temporal regions C) Significant regression of lesions after two months. D) After six months.
treatment was stopped, carbohydrate loading, EDTA infusion and physiotherapy were started. Two months later, when she had partially recovered, repeated MRI showed regression of right frontal and both parietal lesions (figure 1E,F). Six months later, she was able to walk with assistance and one year later she recovered completely and seizures were well controlled.
Case 2
In December 2006, a 22-year-old woman with no family history of porphyria was admitted to the emergency room with confusion, disorientation and agitation. The patient had a medical history of appendectomy one week earlier. There was no focal neurological deficit. Her blood pressure was borderline high at some 657
Reversible MRI Findings of Porphyric Encephalopathy
measurements. Blood tests showed only a mild hyponatremia. MRI of the brain demonstrated hyperintense gyriform lesions on the T2weighted and FLAIR images (figure 2A,B) and hypo and isointense lesions on the T1-weighted images on bilateral frontal, parietal and right occipital and temporal regions. The differential diagnosis included encephalitis, CNS vasculitis, and acute disseminated encephalomyelitis. EEG showed generalized disorganization on both hemispheres. CSF analysis showed 15 mm3 lymphocytes, high protein (82 mg/dl) and normal glucose levels. Since the incidence of tuberculosis is high in our country, chemotherapy was started for the probable diagnosis of tuberculous meningoencephalitis. The next day, her neurological examination returned to normal. On the third day, she suffered severe diffuse abdominal pain which did not respond to analgesics. Abdominal examination, ultrasonography and gastroscopy were normal. Abdominal pain was followed by nausea, vomiting, loss of appetite, and constipation. Porphyria was considered in the differential diagnosis due to the existence of the neuropsychiatric symptoms, abdominal pain and dysautonomia. A urine sample was examined and high urinary porphyrin profiles confirmed the diagnosis of porphyria. Chemotherapy for tuberculosis was stopped and she was treated with carbohydrate loading. Her abdominal pain regressed in a few days and did not recur. The cranial MRI performed two and six months later revealed that the lesions determined on first MRI were significantly regressed (figure 2C,D, respectively). Discussion Porphyrias are seven different diseases that are caused by hereditary or acquired defects of heme biosynthesis in which CNS involvement can lead to porphyric encephalopathy. Clinical manifestations of CNS involvement are epileptic seizures, impaired consciousness, behavior changes (anxiety, agitation, confusion, hallucinations etc.) and hyponatremia caused by inappropriate antidiuretic hormone syndrome. Eventually, somnolence and coma may result. Patients also suffer severe abdominal pain, nausea, constipation, labile hypertension and sensorimotor neuropathy caused by autonomic and peripheral nervous system involvement 1-4. There are only a few reported neuropsychiatric porphyria cases in which cranial MRI 658
A. Soysal
abnormalities are shown 5-10. Firstly, King and Bragdon reported transient cranial MRI abnormalities determined during an acute episode of porphyria with neurological symptoms and suggested vasospasm as the cause of these 5. Aggarwal et Al showed transient changes in the cerebral cortex on MRI that resolved on follow-up imaging correlated with the resolution of neurological symptoms and considered that cerebral changes were due to an ischemic vasculopathy 6. Black et Al reported transient cerebral vasospasm demonstrated by both MR angiography and conventional angiography in a case with neurological symptoms of acute porphyria attack and proposed transient vasoreactive ischemia as the cause of cerebral symptoms in porphyric encephalopathy 7. Utz et Al demonstrated reversible cranial MRI lesions in a case with AIP and attributed these lesions and clinical abnormalities to a vascular origin associated with hypertensive encephalopathy 8. Similarly, Celik et Al reported transient MRI findings in a woman with eclampsia in the 38th week of pregnancy diagnosed as AIP and suggested a similar mechanism to posterior reversible encephalopathy syndrome (PRES) underlying cerebral symptoms in porphyria 9. Maramattom et Al demonstrated reversible MRI lesions correlated with the vasospasm demonstrated by cerebral angiography in a case with AIP. They considered the reversible MRI lesions denote a vasogenic edema with temporary breakdown of the blood-brain barrier, possibly induced by heme biosynthetic pathway intermediates and different from lesions of PRES by their contrast enhancement 10 . The MRI findings of our two AIP patients demonstrated reversible multifocal, cortical, diffuse hyperintense lesions and are consistent with earlier reports 5-10. We suggest that these findings are related to reversible ischemic vasculopathy as documented with cerebral angiography in two reports 7-10. The exact mechanism of reversible ischemic vasculopathy is not clear. It is proposed that during acute episodes, a decrease in cerebral nitric oxide (NO) which is synthesized by a flavo-hemoprotein can induce cerebral vasoconstriction since NO is a potent vasodilator 1,2,8. The other proposed mechanisms for the MRI abnormalities include neurotoxicity of porphyrin precursors, aminolevulinic acid, free radicals and deficiency of heme proteins 1,2,4,6,9,10. Neuropsychiatric porphyria with cranial MRI abnormalities is rare and few cases have been reported. We diagnosed only two cases in the
www. centauro. it
last eleven years in our clinic. In conclusion, we emphasize that since the porhyria can be fatal, it should be considered when there are
The Neuroradiology Journal 21: 655-659, 2008
neuropsychiatric symptoms associated with abdominal pain to prevent misdiagnosis, inappropriate treatment and surgical interventions.
References 1 Suarez JI, Cohen ML, Larkin J et Al: Acute intermittent porphyria: Clinicopathologic correlation. Neurology 48: 1678-1683, 1997. 2 Meyer UA, Schuurmans MM, Lındberg RP: Acute porphyrias: pathogenesis of neurological manifestations. Semin Liver Dis 18: 43-52, 1998. 3 Gonzalez-Arriaza HL, Bostwick JM: Acute porphyrias: a case report and review. Am J Psychiatry 160: 450459, 2003. 4 Kauppinen R: Porphyrias. Lancet 365: 241-252, 2005. 5 King PH, Bragdon AC: MRI reveals multiple reversible cerebral lesions in an attack of acute intermittent porphyria. Neurology 41: 1300-1302, 1991. 6 Aggarwal A, Quint DJ, Lynch JP: MR imaging of porphyric encephalopathy. Am J Roentgenol 162: 12181220, 1994. 7 Black KS, Mirsky P, Kalina P et Al: Angiographic demostration of reversible cerebral vasospasm in porphyric encephalopathy. Am J Neuroradiol 16: 1650-1652, 1995. 8 Utz N, Kinkel B, Hedde JP et Al: MR imaging of acute intermittent porphyria mimicking reversible posterior leukoencephalopathy syndrome. Neuroradiology 43: 1059-1062, 2001.
9 Çelik M, Forta H, Dalkılıç T et Al: MRI reveals reversible lesions resembling posterior reversible encephalopathy in porphyria. Neuroradiology 44: 839-841, 2002. 10 Maramattom BV, Zaldivar RA, Glynn SM et Al: Acute intermittent porphyria presenting as a diffuse encephalopathy. Ann Neurol 57: 581-584, 2005.
Aysun Soysal, MD Neurology Department Bakirkoy Research and Training Hospital for Psychiatry Neurology and Neurosurgery Zuhuratbaba Mah. Bakirkoy 34740 Istanbul, Turkey E-mail: [email protected]
659
