1. T2 FLAIR Increased Signal Intensity at the Posterior Limb of the Internal Capsule: Clinical Significance in ALS Patients G. Protogerou 1, S. Ralli 2, I. Tsougos 3, I. Patramani 2, G. M. Hatjigeorgiou 2, I. Fezoulidis 1, E.Z. Kapsalaki 1 Depts 1. Radiology, 2. Neurology, 3. Physics University Hospital of Larisa, School of Medicine, University of Thessaly, Larisa, Greece XIX Symposium Neuroradiologicum, Bologna, Italy, October 4-9, 2010

2. Amyotrophic lateral sclerosis (ALS) is the most common form of Motor Neuron Disease (MND) characterized by progressive upper and lower motor neuron degeneration. T2 hyperintensity along the corticospinal tract has been reported with variable specificity Possible explanation is loss of myelinated fibers following motor neuron degeneration (*) but this finding has been also identified in healthy controls. Correlation with disease progression has not been established yet. (* Hecht MJ, Fellner F, Fellner C, Hilz MJ, Neundörfer B, Heuss D. Hyperintense and hypointense MRI signals of the precentral gyrus and corticospinal tract in ALS: a follow-up examination including FLAIR images. J Neurol Sci. 2002 Jul 15;199(1-2):59-65.)‏ INTRODUCTION

3.  to evaluate the frequency with which hyperintense T2 signal appears at the posterior limb of the internal capsule (PLIC) of ALS patients and its clinical significance  compare visual with quantitative measurements  correlate quantitative measurements with the progression of the disease PURPOSE

4.  on-going prospective clinical study  24 patients (14 males, 10 females aged 18-76)  51 normal controls.  ALS patient group all patients were neurologically examined and underwent intensive diagnostic procedures (electrodiagnostic examination- electromyography EMG, laboratory investigations of the blood and the corticospinal fluid and neuroimaging of the brain and spine) in order to exclude other diseases, resembling ALS neurological evaluation estimated symptoms from the upper and lower motor neurons. diagnosis was established according to the criteria of El Escorial in the revised form of Airlee House. PATIENTS AND METHODS

5. Our patients underwent the initial MRI, 6 months to 2 years from onset of their symptomatology. Follow up MRIs were performed in 9/24 patients in periods of at least 6 months. All 51 controls were healthy volunteers without any signs or symptoms of an internal or neurologic disease. At the time of the initial MRI investigation 5 patients had been diagnosed with definite ALS, 11 patients with probable ALS, 7 patients with possible ALS, 1 patient with suspected ALS.

6. MRI examinations were performed on a 3-T unit (HDxT, GE Healthcare, Medical Systems, Milwaukee, USA). Our protocol includes:  axial T2W images  FLAIR images  DWI  DTI and  3D-SPGR images Intravenous contrast is administered at the initial MRI scan. MRI PROTOCOL

7. Signal changes were visually evaluated by three experienced neuroradiologists in consensus, blinded to the clinical results. MRI findings evaluated:  T2 FLAIR signal changes in the PLIC Signal changes are classified (*) as no signal change “mild” hyperintense if the signal was isointense or of similar intensity to the caput of the caudate nucleus “distinct” hyperintense if the signal was isointense or of similar intensity to the insular cortex,  Fractional anisotropy (FA) measurements are performed by placing a region of interest (ROI) in PLIC bilaterally.  Both findings are being compared. (* Hecht MJ, Fellner F, Fellner C, Hilz MJ, Heuss D, Neundörfer B. MRI-FLAIR images of the head show corticospinal tract alterations in ALS patients more frequently than T2-, T1- and proton-density-weighted images. J Neurol Sci. 2001 May 1;186(1-2):37-44. )‏

8. Control group No signal change Control group Mild signal change ALS Distinct signal change

9. We didn’t anticipate to identify any signal abnormalities in the PLIC of any of the subjects of the control group. In 29/51 controls faint hyperintensities could be identified in the PLIC but only 10/51 fulfilled the criteria mentioned before by all the examiners and were characterized “mild”. The rest (19/51) were finally classified as no signal abnormality. This finding is in accordance with existing reports of signal hyperintesities in the PLIC of normal controls (*)‏ (* Mirowitz S, Sartor K, Gado M, Torack R Focal signal-intensity variations in the posterior internal capsule: normal MR findings and distinction from pathologic findings. Radiology. 1989 Aug;172(2):535-9.)‏ RESULTS

10. No signal changes were identified in the PLIC in 51 /75 subjects. 41/51 were healthy controls and 10/24 were ALS patients. No signal changes 51/75Controls41/51 ALS10/24 Regarding our 10 ALS patients three had definite ALS four probable (one with bulbar onset) ALS two possible ALS one suspected ALS.

11. Mild signal changes were visualized in the PLIC in 17 / 75 subjects. Of these 10 / 51 were healthy volunteers and 7 / 24 were ALS patients. Mild signal changes 17/75Controls10/51 ALS7/24 Of the 7 ALS patients five had possible ALS two had probable ALS

12. FLAIR images Mild signal changes in the PLIC in 2 different patients

13. In the remaining 7 / 24 ALS patients distinct T2 FLAIR signal changes were visualized in the PLIC (Four males aged 36-40 yo, one male aged 60 yo, one male aged 75 yo and one single female aged 58 yo)‏ No distinct signal change was visualized in the controls Two of the ALS patients were initially classified as having definite ALS and five (5) were classified as having probable ALS, but in the course of the disease four (4) of them deteriorated and finally developed definite ALS. 1 st Classification 2 nd Classification ALS Patients 77 Probable51 Definite26

14. FLAIR images Distinct signal changes in the PLIC in 5 different patients

15. Follow up MRI was performed in nine ALS patients, four of which had distinct signal changes in the PLIC. Three of these patients deteriorated or developed definite ALS in the progress of the disease, thus changing diagnosting category according to the revised El Escorial criteria. The follow up examination disclosed that the increased T2 FLAIR signal change got either more accentuated or more extended craniocaudally to the corona radiata/centum semiovale and the crus cerebri, demarkating the CST

16. 1 st MRI 2 nd MRI

17. 1 st MRI 2 nd MRI

18. In an attempt to quantitate the increased T2 signal we calculated Fractional Anisotropy (FA) at the PLIC of patients with distinct signal changes, using the Region Of Interest method.

19. Comparing (FA) measurements, between controls and patients we found that FA measurements in patients were lower than in the age matched healthy subjects. A further decrease in FA measurements was also noticed with disease progression on the F/U study. Using fiber tractography we visualized the CST tract in healthy volunteers as well as ALS patients. A small number of patients, especially those with definite ALS, showed a visibly decreased volume of CST fibre bundles

20. 0,780+/-0,103 0,749+/-0,122 0,805+/-0,0752 0,819+/-0,139

21. Mean FA Measurements PatientsControls LeftRightLeftRight 0,661+/- 0,080,662+/-0,070,730+/-0,090,717+/-0,08

22. FA measurements Patient No Exam No LeftRight11st0,718+/-0,04930,693+/-0,0474 0,666+/-0,07970,713+/-0,0754 2nd0,648+/-0,06500,637+/-0,0387 0,712+/-0,1130,689+/-0,0975 21st0,690+/-0,06210,674+/-0,0447 0,705+/-0,06790,756+/-0,0523 2nd0,549+/-0,03700,547+/-0,0371 0,643+/-0,07730,652+/-0,0770 31st0,699+/-0,1050,563+/-0,0777 0,690+/-0,1050,735+/-0,117 2nd0,450+/-0,05010,469+/-0,0814 0,521+/-0,09790,506+/-0,0821 41st0,664+/-0,05050,621+/-0,0909 0,610+/-0,1330,655+/-0,132 2nd0,654+/-0,02930,647+/-0,0547 0,627+/-0,07790,644+/-0,0849 Follow up

23. Normal tract ALS patient tract

24. Our findings indicate that  mild hyperintensity of the PLIC is not pathognomonic for ALS  detection of a distinct PLIC hyperintensity that gradually accentuates might actually be a sign of progressive ALS, reflecting degeneration and neuronal loss. This finding is also supported by the progressively decreasing FA measurements. Larger numbers of patients need to be included and re-evaluated though, in order to obtain statistically significant results. CONCLUSIONS

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