Cerebral Hypoperfusion in Hereditary Coproporphyria (HCP): A Single Photon Emission Computed Tomography (SPECT) Study

Abstract

Background: Hereditary Coproporphyria (HCP) is characterized by abdominal pain, neurologic symptoms and psychiatric disorders, even if it might remain asymptomatic. The pathophysiology of both neurologic and psychiatric symptoms is not fully understood. Therefore, aiming to evaluate a possible role of brain blood flow disorders, we have retrospectively investigated cerebral perfusion patterns in Single Photon Emission Computed Tomography (SPECT) studies in HCP patients.

Materials & methods: We retrospectively evaluated the medical records of patients diagnosed as being affected by HCP. A total of seven HCP patients had been submitted to brain perfusion SPECT study with 99mTc-Exametazime (hexamethylpropyleneamine oxime, HMPAO) or with its functionally equivalent 99mTc-Bicisate (ECD or Neurolite) according with common procedures. In 3 patients the scintigraphic study had been repeated for a second time after the first evaluation at 3, 10 and 20 months, respectively. All the studied subjects had been also submitted to an electromyographic and a Magnetic Resonance Imaging (MRI) study of the brain.

Results: Mild to moderate perfusion defects were detected in temporal lobes (all 7 patients), frontal lobes (6 patients) and parietal lobes (4 patients). Occipital lobe, basal ganglia and cerebellar involvement were never observed. In the three subjects in which SPECT study was repeated, some recovery of hypo-perfused areas and appearance of new perfusion defects in other brain regions have been found. In all patients electromyography resulted normal and MRI detected few unspecific gliotic lesions only in one patient. Discussion & Conclusions: Since perfusion abnormalities were usually mild to moderate, this can probably explain the normal pattern observed at MRI studies. Compared to MRI, SPECT with 99mTc showed higher sensitivity in HCP patients. Changes observed in HCP patients who had more than one study suggest that transient perfusion defects might be due to a brain artery spasm possibly leading to psychiatric and neurologic symptomatology, as already observed in patients affected by acute intermittent porphyria. This observation, if confirmed by other well designed studies aiming to demonstrate a direct link between artery spasm, perfusion defects and related symptoms could lead to improvements in HCP treatments.

Fig. (1)

Comparison of brain SPECT and MRI findings in a 37yo male (first study). a: mild perfusion defect of right fronto-parietal cortex (arrows) at SPECT. MRI FLAIR sequence shows only minimal unspecific gliotic lesions (arrowheads) close to the hypoperfused area detected by SPECT. b: moderate perfusion defect of right temporal lobe pole at SPECT study. No focal alterations detected with MRI.

Fig. (2)

Comparison of brain SPECT and MRI findings in the same patient of (37yo male) at follow-up. a: disappearance of the previously observed perfusion defect on right fronto-parietal cortex and onset of a new hypoperfused area on left fronto-parietal cortex (arrows). MRI FLAIR shows no significant changes compared with the previous study (arrowheads). DWI shows no significant abnormalities. b: hypoperfusion extension to the left temporal lobe pole at SPECT study (arrows). No focal alterations detected with MRI (FLAIR and DWI).

Fig. (3)

Comparison of brain SPECT and MRI findings in a 15 yo male at baseline and at follow-up. a: Baseline: minimal perfusion defect of right frontal cortex (arrows) and left parieto-occipital border (arrowheads) at SPECT. No focal alterations detected with MRI (FLAIR and DWI). b: Follow-up: disappearance of the previously observed perfusion defects and onset of a new minimal hypoperfused area on left fronto-parietal cortex (arrows). No focal alterations detected with MRI (FLAIR and DWI).