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Neuroradiology

, Volume 49, Issue 11, pp 927–931 | Cite as

MRI at 3 Tesla detects no evidence for ischemic brain damage in intensively treated patients with homozygous familial hypercholesterolemia

  • Stephan A. Schmitz
  • Declan P. O’Regan
  • Julie Fitzpatrick
  • Clare Neuwirth
  • Elizabeth Potter
  • Isabella Tosi
  • Joseph V. Hajnal
  • Rossi P. Naoumova
Diagnostic Neuroradiology

Abstract

Introduction

Homozygous familial hypercholesterolemia (FH) is considered a model disease for excessive plasma cholesterol levels. Patients with untreated homozygous FH have a markedly increased risk for premature atherosclerosis. The frequency and extent of ischemic brain damage detectable by high-field magnetic resonance imaging (MRI) after long-term intensive treatment are unknown.

Methods

In a case control study, five patients with homozygous FH (one male and four females; mean age: 23.6 ± 9.2, range: 12–36 years; mean pre-treatment serum total cholesterol level: 26.9 ± 3.24 mmol/L; all patients with documented atherosclerotic plaques in the carotid arteries) and five age- and sex-matched healthy controls were studied. All patients had been on maximal lipid-lowering medication since early childhood, and four of them were also on treatment with low-density lipoprotein (LDL) apheresis at bi-weekly intervals. Brain MRI was performed at 3 Tesla field strength with fluid-attenuated T2-weighted inversion recovery and T1-weighted spin-echo MR pulse sequences and subsequently evaluated by two independent readers.

Results

The maximal lipid-lowering treatment reduced the total serum cholesterol by more than 50% in the patients, but their serum concentrations were still 3.6-fold higher than those found in the controls (11.9 ± 4.2 vs. 4.5 ± 0.5 mmol/L;  p < 0.0047). No brain abnormality was observed in any of the patients with homozygous FH.

Conclusion

Homozygous FH patients on intensive cholesterol-lowering therapy have no evidence of ischemic brain damage at 3 Tesla MRI despite the remaining high cholesterol levels.

Keywords

Brain infarction Dementia Homozygous familial hypercholesterolemia Magnetic resonance imaging White matter lesions 

Notes

Conflict of interest statement

Declan O’Regan receives a PhD stipend from Schering Health Care UK.

References

  1. 1.
    Amarenco P, Cohen A, Tzourio C, Bertrand B, Hommel M, Besson G, Chauvel C, Touboul PJ, Bousser MG (1994) Atherosclerotic disease of the aortic arch and the risk of ischemic stroke. N Engl J Med 331:1474–1479PubMedCrossRefGoogle Scholar
  2. 2.
    Amarenco P, Labreuche J, Elbaz A, Touboul PJ, Driss F, Jaillard A, Bruckert E (2006) Blood lipids in brain infarction subtypes. Cerebrovasc Dis 22:101–108PubMedCrossRefGoogle Scholar
  3. 3.
    Autti T, Raininko R, Vanhanen SL, Kallio M, Santavuori P (1994) MRI of the normal brain from early childhood to middle age. I. Appearances on T2- and proton density-weighted images and occurrence of incidental high-signal foci. Neuroradiology 36:644–648PubMedCrossRefGoogle Scholar
  4. 4.
    Baum KA, Schulte C, Girke W, Reischies FM, Felix R (1996) Incidental white-matter foci on MRI in “healthy” subjects: evidence of subtle cognitive dysfunction. Neuroradiology 38:755–760PubMedCrossRefGoogle Scholar
  5. 5.
    Braffman BH, Zimmerman RA, Trojanowski JQ, Gonatas NK, Hickey WF, Schlaepfer WW (1988) Brain MR: pathologic correlation with gross and histopathology. 2. Hyperintense white-matter foci in the elderly. AJR Am J Roentgenol 151:559–566PubMedGoogle Scholar
  6. 6.
    de Leeuw FE, de Groot JC, Achten E, Oudkerk M, Ramos LM, Heijboer R, Hofman A, Jolles J, van Gijn J, Breteler MM (2001) Prevalence of cerebral white matter lesions in elderly people: a population based magnetic resonance imaging study. The Rotterdam Scan Study. J Neurol Neurosurg Psychiatry 70:9–14PubMedCrossRefGoogle Scholar
  7. 7.
    Goldstein J, Hobbs H, Brown M (1994) Familial Hypercholesterolaemia. In: Scriver C, Beaudet A, Sly W, Valle D (eds) The metabolic and molecular basis of inherited disorders. McGraw Hill, New York, pp 1981–2030Google Scholar
  8. 8.
    Horikoshi T, Yagi S, Fukamachi A (1993) Incidental high-intensity foci in white matter on T2-weighted magnetic resonance imaging. Frequency and clinical significance in symptom-free adults. Neuroradiology 35:151–155PubMedCrossRefGoogle Scholar
  9. 9.
    Law MR, Wald NJ, Rudnicka AR (2003) Quantifying effect of statins on low density lipoprotein cholesterol, ischaemic heart disease, and stroke: systematic review and meta-analysis. Br Med J 326:1423PubMedCrossRefGoogle Scholar
  10. 10.
    Naoumova RP, Thompson GR, Soutar AK (2004) Current management of severe homozygous hypercholesterolaemias. Curr Opin Lipidol 15:413–422PubMedCrossRefGoogle Scholar
  11. 11.
    Postiglione A, Nappi A, Brunetti A, Soricelli A, Rubba P, Gnasso A, Cammisa M, Frusciante V, Cortese C, Salvatore M et al (1991) Relative protection from cerebral atherosclerosis of young patients with homozygous familial hypercholesterolemia. Atherosclerosis 90:23–30PubMedCrossRefGoogle Scholar
  12. 12.
    Soljanlahti S, Autti T, Lauerma K, Raininko R, Keto P, Turtola H, Vuorio AF (2005) Familial hypercholesterolemia patients treated with statins at no increased risk for intracranial vascular lesions despite increased cholesterol burden and extracranial atherosclerosis. Stroke 36:1572–1574PubMedCrossRefGoogle Scholar
  13. 13.
    Thompson GR, Miller JP, Breslow JL (1985) Improved survival of patients with homozygous familial hypercholesterolaemia treated with plasma exchange. Br Med J (Clin Res Edn) 291:1671–1673CrossRefGoogle Scholar
  14. 14.
    Tosi I, Toledo-Leiva P, Neuwirth C, Naoumova RP, Soutar AK (2007) Genetic defects causing familial hypercholesterolaemia: Identification of deletions and duplications in the LDL-receptor gene and summary of all mutations found in patients attending the Hammersmith Hospital Lipid Clinic. Atherosclerosis (in press) (Epub: 13 November 2006) DOI  10.1016/j.atherosclerosis.2006.10.003
  15. 15.
    Vaughan CJ, Delanty N (1999) Neuroprotective properties of statins in cerebral ischemia and stroke. Stroke 30:1969–1973PubMedGoogle Scholar
  16. 16.
    Vermeer SE, Hollander M, van Dijk EJ, Hofman A, Koudstaal PJ, Breteler MM (2003) Silent brain infarcts and white matter lesions increase stroke risk in the general population: the Rotterdam Scan Study. Stroke 34:1126–1129PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Stephan A. Schmitz
    • 1
  • Declan P. O’Regan
    • 1
  • Julie Fitzpatrick
    • 1
  • Clare Neuwirth
    • 2
    • 3
  • Elizabeth Potter
    • 2
    • 3
  • Isabella Tosi
    • 2
    • 3
  • Joseph V. Hajnal
    • 1
  • Rossi P. Naoumova
    • 2
    • 3
  1. 1.Imaging Sciences Department, MRC Clinical Sciences Centre, Faculty of Medicine, Imperial CollegeHammersmith Hospital CampusLondonUK
  2. 2.Clinical Research FacilityMRC Clinical Sciences CentreLondonUK
  3. 3.Lipid ClinicHammersmith HospitalLondonUK

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