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2013, :. doi:
2013-11-18T11:25:49+08:00
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Thor D Stein
Victor E Alvarez
Ann C McKee
Chronic traumatic encephalopathy: a spectrum of neuropathological changes following repetitive brain trauma in athletes and military personnel
2013, :. doi:
� 2013 BioMed Central Ltd.
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Q
q
1 0 0 1 56.6930007935 689.7260131836 cm
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Q
q
1 0 0 1 56.6930007935 700.7239990234 cm
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B*
Q
q
1 0 0 1 535.5780029297 703.6719970703 cm
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B*
Q
q
1 0 0 1 538.5830078125 700.7239990234 cm
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-2.4949998856 0 l
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Q
q
1 0 0 1 538.5830078125 689.7260131836 cm
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B*
Q
q
1 0 0 1 535.5780029297 686.7210083008 cm
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-475.8800048828 0 l
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Q
q
1 0 0 1 59.6980018616 686.7210083008 cm
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B*
Q
q
1 0 0 1 56.6930007935 689.7260131836 cm
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B*
Q
q
1 0 0 1 56.6930007935 700.7239990234 cm
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B*
Q
q
1 0 0 1 56.6930007935 538.1859741211 cm
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0 9.5240001678 l
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B*
Q
q
1 0 0 1 56.6930007935 547.7100219727 cm
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0.057 0.6800000072 l
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3.4019999504 3.4579999447 l
1.9869999886 3.1570000648 0.8270000219 2.0959999561 0.5669999719 0.6240000129 c
0.5099999905 0 l
B*
Q
q
1 0 0 1 60.7179985046 551.6790161133 cm
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473.8389892578 0 l
473.8389892578 -0.4530000091 l
0 -0.4530000091 l
B*
Q
q
1 0 0 1 534.5570068359 551.6790161133 cm
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0 -0.4539999962 l
B*
Q
q
1 0 0 1 538.5830078125 547.7100219727 cm
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0 -9.5240001678 l
-0.5099999905 -9.5240001678 l
-0.5099999905 0 l
B*
Q
q
1 0 0 1 534.5570068359 551.2249755859 cm
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-473.8389892578 0 l
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B*
Q
q
1 0 0 1 538.5830078125 538.1859741211 cm
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-0.5099999905 0 0.5102499723 -6.0093998909 re
B*
Q
q
1 0 0 1 56.6930007935 532.1760253906 cm
0 0 m
0.5099999905 0 -0.5102400184 6.0095000267 re
B*
Q
q
1 0 0 1 538.5830078125 532.1760253906 cm
0 0 m
-0.5099999905 0 0.5102499723 -11.9619998932 re
B*
Q
q
1 0 0 1 56.6930007935 520.2139892578 cm
0 0 m
0.5099999905 0 -0.5102400184 11.9619998932 re
B*
Q
q
1 0 0 1 538.5830078125 520.2139892578 cm
0 0 m
-0.5099999905 0 0.5102499723 -12.0190000534 re
B*
Q
q
1 0 0 1 56.6930007935 508.1950073242 cm
0 0 m
0.5099999905 0 -0.5102400184 12.0190000534 re
B*
Q
q
1 0 0 1 538.5830078125 508.1950073242 cm
0 0 m
-0.5099999905 0 0.5102499723 -12.0190000534 re
B*
Q
q
1 0 0 1 56.6930007935 496.175994873 cm
0 0 m
0.5099999905 0 -0.5102400184 12.0190000534 re
B*
Q
q
1 0 0 1 538.5830078125 496.175994873 cm
0 0 m
-0.5099999905 0 0.5102499723 -11.9619998932 re
B*
Q
q
1 0 0 1 56.6930007935 484.2139892578 cm
0 0 m
0.5099999905 0 -0.5102400184 11.9619998932 re
B*
Q
q
1 0 0 1 538.5830078125 484.2139892578 cm
0 0 m
-0.5099999905 0 0.5102499723 -12.0190000534 re
B*
Q
q
1 0 0 1 56.6930007935 472.1950073242 cm
0 0 m
0.5099999905 0 -0.5102400184 12.0190000534 re
B*
Q
q
1 0 0 1 538.5830078125 472.1950073242 cm
0 0 m
-0.5099999905 0 0.5102499723 -12.0190000534 re
B*
Q
q
1 0 0 1 56.6930007935 460.175994873 cm
0 0 m
0.5099999905 0 -0.5102400184 12.0190000534 re
B*
Q
q
1 0 0 1 538.5830078125 460.175994873 cm
0 0 m
-0.5099999905 0 0.5102499723 -11.9619998932 re
B*
Q
q
1 0 0 1 56.6930007935 448.2139892578 cm
0 0 m
0.5099999905 0 -0.5102400184 11.9619998932 re
B*
Q
q
1 0 0 1 538.5830078125 448.2139892578 cm
0 0 m
-0.5099999905 0 0.5102499723 -12.0190000534 re
B*
Q
q
1 0 0 1 56.6930007935 436.1950073242 cm
0 0 m
0.5099999905 0 -0.5102400184 12.0190000534 re
B*
Q
q
1 0 0 1 538.5830078125 436.1950073242 cm
0 0 m
-0.5099999905 0 0.5102499723 -12.0190000534 re
B*
Q
q
1 0 0 1 56.6930007935 424.175994873 cm
0 0 m
0.5099999905 0 -0.5102400184 12.0190000534 re
B*
Q
q
1 0 0 1 538.5830078125 424.175994873 cm
0 0 m
-0.5099999905 0 0.5102499723 -11.9619998932 re
B*
Q
q
1 0 0 1 56.6930007935 412.2139892578 cm
0 0 m
0.5099999905 0 -0.5102400184 11.9619998932 re
B*
Q
q
1 0 0 1 538.5830078125 412.2139892578 cm
0 0 m
-0.5099999905 0 0.5102499723 -12.0190000534 re
B*
Q
q
1 0 0 1 56.6930007935 400.1950073242 cm
0 0 m
0.5099999905 0 -0.5102400184 12.0190000534 re
B*
Q
q
1 0 0 1 538.5830078125 400.1950073242 cm
0 0 m
-0.5099999905 0 0.5102499723 -12.0190000534 re
B*
Q
q
1 0 0 1 56.6930007935 388.175994873 cm
0 0 m
0.5099999905 0 -0.5102400184 12.0190000534 re
B*
Q
q
1 0 0 1 538.5830078125 388.175994873 cm
0 0 m
-0.5099999905 0 0.5102499723 -11.9619998932 re
B*
Q
q
1 0 0 1 56.6930007935 376.2139892578 cm
0 0 m
0.5099999905 0 -0.5102400184 11.9619998932 re
B*
Q
q
1 0 0 1 538.5830078125 376.2139892578 cm
0 0 m
-0.5099999905 0 0.5102499723 -12.0190000534 re
B*
Q
q
1 0 0 1 56.6930007935 364.1950073242 cm
0 0 m
0.5099999905 0 -0.5102400184 12.0190000534 re
B*
Q
q
1 0 0 1 538.5830078125 364.1950073242 cm
0 0 m
-0.5099999905 0 0.5102499723 -12.0190000534 re
B*
Q
q
1 0 0 1 56.6930007935 352.175994873 cm
0 0 m
0.5099999905 0 -0.5102400184 12.0190000534 re
B*
Q
q
1 0 0 1 538.5830078125 352.175994873 cm
0 0 m
-0.5099999905 0 0.5102499723 -11.9619998932 re
B*
Q
q
1 0 0 1 56.6930007935 340.2139892578 cm
0 0 m
0.5099999905 0 -0.5102400184 11.9619998932 re
B*
Q
q
1 0 0 1 538.5830078125 340.2139892578 cm
0 0 m
-0.5099999905 0 0.5102499723 -12.0190000534 re
B*
Q
q
1 0 0 1 56.6930007935 328.1950073242 cm
0 0 m
0.5099999905 0 -0.5102400184 12.0190000534 re
B*
Q
q
1 0 0 1 538.5830078125 328.1950073242 cm
0 0 m
0 -2.493999958 l
-0.5099999905 -2.493999958 l
-0.5099999905 0 l
B*
Q
q
1 0 0 1 538.5830078125 325.7009887695 cm
0 0 m
-0.057 -0.6800000072 l
-0.2479999959 -2.2000000477 -1.7300000191 -3.7400000095 -3.2880001068 -3.9119999409 c
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-1.9309999943 -3.111000061 -0.8439999819 -2.1549999714 -0.5669999719 -0.6240000129 c
-0.5099999905 0 l
B*
Q
q
1 0 0 1 534.5570068359 321.675994873 cm
0 0 m
-473.8389892578 0 l
-473.8389892578 0.5099999905 l
0 0.5099999905 l
B*
Q
q
1 0 0 1 60.7179985046 321.675994873 cm
0 0 m
-0.7369999886 0.112999998 l
-2.2960000038 0.2860000134 -3.7769999504 1.8250000477 -3.9690001011 3.3450000286 c
-4.0250000954 4.0250000954 l
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-3.4579999447 3.4019999504 l
-3.1809999943 1.8700000048 -2.0940001011 0.9139999747 -0.6240000129 0.5669999719 c
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B*
Q
q
1 0 0 1 56.6930007935 325.7009887695 cm
0 0 m
0 2.493999958 l
0.5099999905 2.493999958 l
0.5099999905 0 l
B*
Q
BT
/F1 1 Tf
13 0 0 13 60.7181015015 690.6895751953 Tm
0 0 0 0 k
0.1163000017 Tc
0 Tw
(REVIEW) Tj
/F2 1 Tf
22.7999000549 0 0 24.0000991821 56.6929016113 652.7053222656 Tm
0 0 0 1 k
0 Tc
[(Chronic) -303.5 (traumatic) -305.299987793 (encephalopathy:) -303.799987793 (a) -299.299987793 (spectrum) -305.1000061035 (of) ] TJ
0 -1.0842000246 TD
[(neuropathological) -306.6000061035 (changes) -300.1000061035 (following) -304.299987793 (repetitive) ] TJ
0 -1.0819000006 TD
[(brain) -300.299987793 (trauma) -303.799987793 (in) -300.6000061035 (athletes) -301.5 (and) -301.700012207 (military) -303 (personnel) ] TJ
/F3 1 Tf
10.4498996735 0 0 11.0001001358 56.6929016113 576.6801757812 Tm
[(Thor) -299.3999938965 (D) -304.3999938965 (Stein) ] TJ
7.8372001648 0 0 7.3326997757 109.3606033325 581.6124267578 Tm
(1,2,3,4,5) Tj
10.4498996735 0 0 11.0001001358 133.3417053223 576.6801757812 Tm
[(,) -300.6000061035 (Victor) -302.6000061035 (E) -301.5 (Alvarez) ] TJ
7.8372001648 0 0 7.3326997757 202.8471984863 581.6124267578 Tm
(2,4,6) Tj
10.4498996735 0 0 11.0001001358 219.8551025391 576.6801757812 Tm
[(and) -298.3999938965 (Ann) -302.700012207 (C) -300.6000061035 (McKee) ] TJ
7.8372001648 0 0 7.3326997757 295.9937133789 581.6124267578 Tm
(1,3,4,5,6*) Tj
/F1 1 Tf
10.3000001907 0 0 10.3000001907 63.212600708 538.1857299805 Tm
(Abstract) Tj
/F3 1 Tf
10.0001001358 0 0 10.0001001358 63.212600708 520.2141113281 Tm
[(Chronic) -304.8999938965 (traumatic) -304.6000061035 (ence) -7.1999998093 (phalopathy) -308.6000061035 (\(CTE\)) -303.799987793 (is) -301.1000061035 (a) -301.299987793 (progressive) -311.299987793 (neurodegenerative) -310.1000061035 (disease) -309.799987793 (that) -300.200012207 (occurs) -305.700012207 (in) -304.1000061035 (association) -307.200012207 (with) ] TJ
0 -1.2019000053 TD
[(repetitive) -306.200012207 (traumatic) -304.6000061035 (br) -7.0999999046 (ain) -299.3999938965 (injury) -305.200012207 (experienced) -306.799987793 (in) -304.1000061035 (sport) -301.1000061035 (and) -306.5 (military) -307.200012207 (service.) -303.799987793 (In) -304.1000061035 (most) -304.1000061035 (instances,) -304 (the) -303.799987793 (clinical) -303.700012207 (symptom) -10.8000001907 (s) ] TJ
T*
[(of) -297.5 (the) -303.799987793 (disease) -304.200012207 (begin) -307.8999938965 (after) -301.6000061035 (a) -301.299987793 (long) -303.700012207 (period) -306 (of) -303.200012207 (latency) -305.5 (ranging) -305.8999938965 (from) -300 (severa) -10.1999998093 (l) -296.6000061035 (years) -306.3999938965 (to) -300.8999938965 (several) -306.799987793 (decades.) -304.799987793 (The) -306.5 (initial) ] TJ
0 -1.1962000132 TD
[(symptoms) -298.799987793 (are) -296.700012207 (typically) -301.299987793 (insidious,) -304.8999938965 (consisting) -297.3999938965 (of) -297.5 (irritability,) -304.6000061035 (impulsivity,) -301.6000061035 (aggression) -11.6999998093 (,) -293.200012207 (depression,) -301.299987793 (short-term) -301.799987793 (memory) -300.3999938965 (loss) ] TJ
0 -1.2019000053 TD
[(and) -300.8999938965 (heightened) -310.299987793 (suicidality.) -308.1000061035 (The) -300.799987793 (symptoms) -310.1000061035 (progress) -305.799987793 (slowly) -306.299987793 (over) -304.299987793 (decades) -306.3999938965 (to) -300.8999938965 (include) -301.8999938965 (co) -7.0999999046 (gnitive) -300.1000061035 (def) -6.9000000954 (icits) -300.8999938965 (and) -306.5 (dementia.) ] TJ
T*
[(The) -300.799987793 (pathology) -302.1000061035 (of) -303.200012207 (CTE) -302.200012207 (is) -295.3999938965 (cha) -8 (racterized) -302.6000061035 (by) -303.299987793 (the) -298.1000061035 (accumulatio) -12.3000001907 (n) -296.700012207 (o) 0 (f) -303.200012207 (phosphorylat) -11.8000001907 (ed) -300.8999938965 (tau) -301.3999938965 (protein) -303.200012207 (in) -298.5 (neurons) -302 (and) -306.5 (astrocytes) ] TJ
0 -1.1962000132 TD
[(in) -298.5 (a) -301.299987793 (pattern) -304.5 (tha) -6.9000000954 (t) -298.8999938965 (i) 0 (s) -301.1000061035 (unique) -302.1000061035 (from) -305.700012207 (other) -303.799987793 (tauopathies) -10.8999996185 (,) -298.8999938965 (including) -305.8999938965 (Alzhe) -9.3999996185 (imer) ] TJ
/F4 1 Tf
28.6581001282 0 TD
<92> Tj
/F3 1 Tf
0.1643999964 0 TD
[(s) -305 (disease.) -302.6000061035 (The) -306.5 (hyperphosphoryl) -12.6000003815 (ated) -300.299987793 (tau) -307.1000061035 (ab-) ] TJ
-28.8225002289 -1.2019000053 TD
[(normalities) -307.6000061035 (begin) -302.200012207 (focally,) -305.1000061035 (as) -305.8999938965 (perivascular) -309 (neurofi) -9 (brillary) -305.700012207 (tangles) -302.799987793 (and) -306.5 (neurites) -307 (at) -299.799987793 (the) -303.799987793 (depths) -303.3999938965 (of) -303.200012207 (the) -298.1000061035 (cerebral) -308 (sulci,) -308 (and) ] TJ
T*
[(then) -300 (spread) -307.700012207 (to) -300.8999938965 (involve) -306.799987793 (superficial) -306 (layer) -8.8999996185 (s) -299.299987793 (o) 0 (f) -297.5 (adjace) -9.1999998093 (nt) -300.8999938965 (cortex) -305.299987793 (before) -304.700012207 (becoming) -308.1000061035 (a) -301.299987793 (widespread) -306.299987793 (degen) -8.6000003815 (eration) -300.799987793 (affect) -9 (ing) ] TJ
0 -1.1962000132 TD
[(medial) -304.1000061035 (temporal) -306.5 (lobe) -304.6000061035 (structures,) -306.700012207 (diencephalo) -10.6999998093 (n) -302.3999938965 (and) -300.8999938965 (brainstem) -10.6000003815 (.) -298.8999938965 (Most) -300.700012207 (instan) -9.5 (ces) -301.700012207 (of) -297.5 (CTE) -307.799987793 (\(>85%) -300.299987793 (of) -303.200012207 (cases\)) -302.299987793 (show) -305.1000061035 (abno) -8 (r-) ] TJ
0 -1.2019000053 TD
[(mal) -296.200012207 (accumulatio) -12.3000001907 (ns) -295.6000061035 (of) -297.5 (phosphory) -10.6999998093 (lated) -296.3999938965 (43) -294.8999938965 (kDa) -300.5 (TAR) -301.5 (DNA) -297 (binding) -300.6000061035 (protein) -303.200012207 (that) -294.6000061035 (are) -302.3999938965 (partially) -301.299987793 (colocalized) -306.200012207 (with) -299 (phosphor-) ] TJ
T*
[(ylated) -301.6000061035 (tau) -307.1000061035 (protein.) -301.6000061035 (As) -305.8999938965 (CTE) -302.200012207 (is) -301.1000061035 (characterized) -310.700012207 (pathologi) -9.5 (cally) -304 (by) -297.6000061035 (frontal) -310 (and) -300.8999938965 (temporal) -306.5 (lobe) -304.6000061035 (atrophy,) -303 (by) -303.299987793 (abno) -8 (rmal) ] TJ
0 -1.1962000132 TD
[(deposits) -304.1000061035 (of) -303.200012207 (phosphorylat) -11.8000001907 (ed) -300.8999938965 (tau) -301.3999938965 (and) -300.8999938965 (by) -303.299987793 (43) -300.6000061035 (kDa) -306.200012207 (TAR) -301.5 (DNA) -302.700012207 (bindin) -8.1999998093 (g) -298 (protein) -303.200012207 (and) -306.5 (is) -301.1000061035 (associated) -307.799987793 (clinically) -310.700012207 (with) -299 (behavior) -11.6999998093 (al) ] TJ
0 -1.2019000053 TD
[(and) -295.200012207 (personality) -304.200012207 (changes,) -296.799987793 (as) -294.5 (well) -297.6000061035 (as) -300.200012207 (cognitive) -295.8999938965 (impair) -10.1999998093 (ments,) -294.1000061035 (CTE) -296.5 (is) -295.3999938965 (increasing) -10.8999996185 (ly) -290.3999938965 (cate) -7.5 (gorized) -296.6000061035 (as) -294.5 (an) -297.6000061035 (acquired) -300.3999938965 (frontotem) -8.8999996185 (-) ] TJ
T*
[(poral) -300.799987793 (lob) -6.9000000954 (ar) -299.5 (degenerati) -10.6999998093 (on.) -302.700012207 (Currently,) -306.299987793 (some) -302.799987793 (of) -303.200012207 (the) -298.1000061035 (great) -9.3000001907 (est) -300.700012207 (challenges) -304.799987793 (are) -302.3999938965 (th) -6.0999999046 (at) -299.799987793 (CTE) -302.200012207 (cannot) -305.1000061035 (be) -300.8999938965 (diagnosed) -307.1000061035 (during) -304.700012207 (life) ] TJ
0 -1.1962000132 TD
[(and) -300.8999938965 (the) -303.799987793 (incidence) -304.6000061035 (and) -306.5 (prevalence) -304.200012207 (of) -303.200012207 (the) -303.799987793 (disorder) -303 (re) -6.6999998093 (main) -303.700012207 (uncertain.) -306 (Furthermore,) -308.6000061035 (the) -303.799987793 (contribution) -311.200012207 (of) -297.5 (age,) -305.8999938965 (gender,) ] TJ
0 -1.2019000053 TD
[(genetics,) -302.799987793 (stres) -8.5 (s,) -297.700012207 (alcohol) -304.5 (and) -306.5 (substance) -306.700012207 (abuse) -307.8999938965 (to) -300.8999938965 (the) -298.1000061035 (develop) -11.1999998093 (ment) -302.5 (of) -297.5 (CTE) -302.200012207 (remain) -10 (s) -299.299987793 (t) 0 (o) -300.8999938965 (b) 0 (e) -300.8999938965 (determined.) ] TJ
/F1 1 Tf
10.3000001907 0 0 10.3000001907 56.6929016113 297.7510986328 Tm
[(Introduc) -10.8000001907 (tion) ] TJ
/F5 1 Tf
9.7999000549 0 0 9.7999000549 56.6929016113 285.732208252 Tm
[(The) -775.700012207 (con) -8.3000001907 (cept) -775.299987793 (that) -780.4000244141 (chronic) -780.299987793 (neurodege) -11.3999996185 (nerati) -9.3999996185 (on) -773.4000244141 (might) ] TJ
0 -1.220600009 TD
[(occur) -435.299987793 (after) -432 (mino) -10.1999998093 (r) -423.299987793 (b) 0 (r) -7.5 (ain) -430.200012207 (trauma) -436.6000061035 (wa) -13 (s) -430.700012207 (first) -432.299987793 (introduced) -437.6000061035 (in) ] TJ
0 -1.2264000177 TD
[(1927) -464.3999938965 (by) -467.700012207 (Osnato) -469.799987793 (and) -465.799987793 (Gilberti) -10.3999996185 (,) -458.799987793 (who) -469.299987793 (studied) -471.3999938965 (100) -461.1000061035 (clin) -8.3000001907 (ical) ] TJ
T*
[(ca) -14.3000001907 (ses) -460.700012207 (of) -461.700012207 (concu) -9.5 (ssion) -460.799987793 (of) -461.700012207 (the) -460.200012207 (br) -7.5 (ain,) -461 (defined) -464.1000061035 (a) -15.8000001907 (s) -459.6000061035 (a) -455.5 (blow) -467.3999938965 (to) ] TJ
0 -1.220600009 TD
[(the) -581.700012207 (head) -579.4000244141 (with) -580.799987793 (loss) -578.9000244141 (of) -577.4000244141 (con) -8.3000001907 (sciousnes) -11.8999996185 (s) -575.299987793 (with) -580.799987793 (or) -574.4000244141 (withou) -11.5 (t) ] TJ
0 -1.2264000177 TD
-0.0142999999 Tc
[(post) 18.3999996185 (-tr) -14.3000001907 (a) 9.3999996185 (umat) -14.3000001907 (i) 12.3000001907 (c) -290.3999938965 (a) 4.5999999046 (m) -2.7999999523 (nesia) -284.6000061035 (o) -3.4000000954 (r) -287.200012207 (s) 0.5 (kull) -286.5 (fractu) -14.3000001907 (r) 10.8000001907 (e,) -288 (and) -281.6000061035 (f) -1 (ound) -287.3999938965 (se) -14.3000001907 (v) 5.5999999046 (e) -1.2000000477 (r) -14.3000001907 (a) 9.3999996185 (l) ] TJ
T*
-0.0141000003 Tc
[(ins) -14.1000003815 (t) 10.3000001907 (ance) 4.8000001907 (s) -265.5 (i) 2.9000000954 (n) -266.200012207 (w) 0.3000000119 (hich) -259.8999938965 (the) -278.700012207 (c) -1 (linical) -263.200012207 (symp) -14.1000003815 (t) 11.6000003815 (o) 2.5999999046 (ms) -259.700012207 (p) -14.1000003815 (e) 9.3999996185 (rsisted) -264.1000061035 (a) -1 (n) 5.6999998093 (d) -264.1000061035 (se) -14.1000003815 (c) 12.1000003815 (-) ] TJ
0 -1.220600009 TD
-0.0142999999 Tc
[(ondary) -429.299987793 (deg) -14.3000001907 (e) 9.1999998093 (n) 5.5 (e) -1.2000000477 (r) -14.3000001907 (a) 9.3999996185 (tive) -440.799987793 (changes) -427.6000061035 (d) 1.7999999523 (e) -14.3000001907 (v) -0.200000003 (eloped,) -432.700012207 (a) -429.299987793 (c) 4.5999999046 (o) -3.4000000954 (ndition) -428.3999938965 (t) 1.1000000238 (hey) ] TJ
0 -1.2264000177 TD
-0.0144999996 Tc
[(termed) -467 (tr) -14.5 (a) 9.1999998093 (u) 0.1000000015 (mat) -14.5 (i) 12.1000003815 (c) -470 (e) -1.3999999762 (ncep) -14.5 (h) 10.3999996185 (a) -1.3999999762 (litis) -468.299987793 ([) -4.9000000954 (1].) -467.6000061035 (S) -2 (ubseq) -14.5 (u) 10.3999996185 (ently,) -467.6000061035 (in) -463.299987793 (1928) ] TJ
T*
0 Tc
[(H) 12.1999998093 (a) 13.1000003815 (r) 16.2999992371 (r) 16.2999992371 (i) 11.1999998093 (s) 14.8000001907 (o) 16.7000007629 (n) -460.3999938965 (M) 13 (a) 13.1000003815 (r) 16.2999992371 (t) 15.3999996185 (l) 11.1999998093 (a) 18.8999996185 (n) 14 (d,) -442.700012207 (a) -461.299987793 (N) 13.6999998093 (e) 13.1000003815 (w) -454.200012207 (J) 11.1999998093 (e) 18.8999996185 (rs) 25.2999992371 (e) 13.1000003815 (y) -455.5 (p) 16.1000003815 (a) 13.1000003815 (th) 24.2000007629 (o) 16.7000007629 (l) 11.1999998093 (o) 16.7000007629 (g) 0 (i) 27.3999996185 (s) 14.8000001907 (t,) -455 (o) 16.7000007629 (u) 14.6000003815 (tl) 26.6000003815 (i) 11.1999998093 (n) 14 (e) 13.1000003815 (d) -452.5 (a) ] TJ
0 -1.220600009 TD
-0.0161000006 Tc
[(sym) -4.5999999046 (p) 0 (to) -5.1999998093 (m) -299.6000061035 (c) -3 (om) -4.5999999046 (pl) -4.9000000954 (ex) -302.299987793 (well) -299.8999938965 (re) -16.1000003815 (cog) -16.1000003815 (n) 8.3000001907 (iz) ] TJ
13.1147003174 0 TD
-0.0144999996 Tc
[(ed) -299.200012207 (in) -295.5 (p) -14.5 (r) 12.1999998093 (ofessional) -298.299987793 (pug) -14.5 (i) 12.8999996185 (list) -14.5 (s) ] TJ
12.1948003769 13.467499733 TD
-0.0142000001 Tc
[(that) -432.700012207 (app) -14.1999998093 (e) 15 (ar) -14.1999998093 (e) 9.5 (d) -426.200012207 (t) -14.1999998093 (o) -416 (r) -14.1999998093 (e) 9.5 (sult) -432.700012207 (from) -430.799987793 (repeated) -431.8999938965 (sublethal) -431.1000061035 (b) -3.2999999523 (lows) -427.5 (t) -14.1999998093 (o) ] TJ
0 -1.2264000177 TD
-0.0144999996 Tc
[(the) -423.700012207 (h) 0.1000000015 (ead) -426.5 ([2].) -421.299987793 (In) -422.799987793 (h) -14.5 (i) 11.3000001907 (s) -422.1000061035 (m) -3 (onograp) -14.5 (h) ] TJ
/F6 1 Tf
13.6700000763 0 TD
0 Tc
<91> Tj
/F5 1 Tf
0.1851000041 0 TD
-0.0137 Tc
[(Punch) -421.3999938965 (D) 3.7000000477 (r) -13.6999998093 (u) 11.3999996185 (nk) ] TJ
/F6 1 Tf
5.623000145 0 TD
0 Tc
<92> Tj
/F5 1 Tf
-0.0057999999 0 TD
-0.0138999997 Tc
[(,) -420.700012207 (M) -0.8999999762 (artland) ] TJ
-19.4724006653 -1.220600009 TD
-0.0140000004 Tc
[(descr) -14 (i) 13.6000003815 (be) 4.9000000954 (d) -420.200012207 (u) 0.6000000238 (nst) -14 (e) 8.6999998093 (adiness) -421.6000061035 (o) 2.7000000477 (f) -423 (g) 2.2000000477 (ait) -14 (,) -417 (mental) -419.299987793 (confusion,) -420.799987793 (slowing) ] TJ
0 -1.2264000177 TD
-0.0130000003 Tc
[(of) -312.1000061035 (muscular) -314.799987793 (mo) 3.7000000477 (vement) -13 (s) -13 (,) -320.200012207 (o) 3.7000000477 (cca) -13 (si) ] TJ
12.796500206 0 TD
-0.0135000004 Tc
[(onally) -318.6000061035 (combined) -315.5 (with) -317.1000061035 (hesi-) ] TJ
-12.796500206 -1.2264000177 TD
-0.0146000003 Tc
[(tancy) -354.3999938965 (i) 2.4000000954 (n) -353.5 (s) 0.200000003 (p) -14.6000003815 (e) 8.8999996185 (e) -14.6000003815 (c) 5.9000000954 (h,) -357.799987793 (tremor) -14.6000003815 (s) -342.200012207 (o) 2.0999999046 (f) -354.200012207 (t) 0.8000000119 (he) -354.3999938965 (hand) -14.6000003815 (s) -342.3999938965 (a) -1.5 (n) 5.1999998093 (d) -357.1000061035 (nod) -14.6000003815 (d) 11.8999996185 (ing) -357.1000061035 (o) 2.0999999046 (f) -354.200012207 (t) 0.8000000119 (he) ] TJ
0 -1.220600009 TD
-0.0142999999 Tc
[(head.) -270.700012207 (T) 9.6000003815 (h) -14.3000001907 (i) 11.5 (s) -271.3999938965 (c) -1.2000000477 (ond) -14.3000001907 (i) 13.1000003815 (tion) -272.200012207 (wa) -14.3000001907 (s) -269.8999938965 (l) 2.7000000477 (at) -14.3000001907 (e) 8.3999996185 (r) -269.8999938965 (referred) -270.1000061035 (t) -14.3000001907 (o) -259.8999938965 (a) -14.3000001907 (s) -269.8999938965 (d) 1.7999999523 (eme) 4.5999999046 (n) -0.3000000119 (t) -14.3000001907 (i) 12.3000001907 (a) -273.1000061035 (p) 1.7999999523 (ug) -14.3000001907 (-) ] TJ
0 -1.2264000177 TD
[(ilist) -14.3999996185 (i) 12.1999998093 (ca) -24.3999996185 (,) -334.3999938965 (t) -14.3999996185 (r) 11.5 (a) -1.2999999523 (umatic) -342.6000061035 (pr) -14.3999996185 (o) 12.8000001907 (g) 1.7999999523 (r) -14.3999996185 (e) 9.3000001907 (ssive) -342.6000061035 (e) 4.5 (n) -0.400000006 (cep) -14.3999996185 (h) 10.5 (a) -1.2999999523 (lopathy,) -340.200012207 (and) -339.6000061035 (c) -1.2999999523 (hronic) ] TJ
T*
[(tr) -14.3000001907 (a) 15.1000003815 (u) -14.3000001907 (m) 11.8000001907 (a) -1.2000000477 (tic) -475.6000061035 (e) -1.2000000477 (ncep) -14.3000001907 (h) 10.6000003815 (a) -1.2000000477 (lopathy) -475.5 (\() 1.1000000238 (C) -25.7000007629 (T) 3.7999999523 (E\)) -473.299987793 (t) -14.3000001907 (o) -462.3999938965 (highlight) -473.299987793 (i) -3.0999999046 (t) -14.3000001907 (s) -470.1000061035 (chronic) ] TJ
0 -1.220600009 TD
0 Tc
[(a) 13.1000003815 (n) 14 (d) -255.8000030518 (p) 16.1000003815 (ro) 27.2000007629 (g) 16.2000007629 (r) 0 (e) 23.7000007629 (s) 14.8000001907 (s) 14.8000001907 (i) 17 (v) 12.6000003815 (e) -258.799987793 (n) 14 (a) 18.8999996185 (tu) 24.2000007629 (r) 16.2999992371 (e) -258.799987793 ([) 15.3999996185 (3) 14.1000003815 (-) 16.8999996185 (7) 14.1000003815 (].) ] TJ
0.8156999946 -1.2264000177 TD
[(Isolate) -10.8000001907 (d) -579.700012207 (repor) -8.1999998093 (t) -13.5 (s) -581.0999755859 (of) -583.200012207 (the) -587.5 (neuropatholog) -13.6000003815 (y) -582.700012207 (o) 0 (f) -583.200012207 (C) -23 (TE) -594.299987793 (ap-) ] TJ
-0.8156999946 -1.2264000177 TD
0.0001 Tc
[(peare) -9.1000003815 (d) -440.799987793 (i) 0.1000000015 (n) -443.299987793 (the) -442.799987793 (literatu) -11 (re) -439 (in) -443.299987793 (the) -448.6000061035 (1950s) -443.799987793 (and) -442.6000061035 (1960s) -443.799987793 ([6-12],) ] TJ
0 -1.220600009 TD
0 Tc
[(but) -317.799987793 (it) -320.5 (wa) -13 (s) -315 (not) -318.3999938965 (unt) -8.1000003815 (il) -313.1000061035 (1973) -319.799987793 (with) -320.5 (the) -321.3999938965 (detaile) -10.8000001907 (d) -313.6000061035 (descrip) -9.1000003815 (tion) -318.700012207 (of) ] TJ
0 -1.2264000177 TD
[(the) -402.3999938965 (clin) -8.3000001907 (ical) -390.8999938965 (and) -396.3999938965 (neuropatholog) -13.6000003815 (ica) -8.8000001907 (l) -387.8999938965 (feature) -11 (s) -390.200012207 (o) 0 (f) -392.299987793 (1) 0 (5) -388.3999938965 (retired) ] TJ
T*
0.0001 Tc
[(boxer) -9.1999998093 (s) -505.799987793 (b) 0.1000000015 (y) -513.9000244141 (Corselli) -9.3000001907 (s) -19.8999996185 (,) -510.799987793 (Bruton) -510.1000061035 (an) -7.5 (d) -504.3999938965 (F) 0.1000000015 (r) -7.4000000954 (eeman-Brow) -12.5 (ne) -510.799987793 ([13]) ] TJ
0 -1.220600009 TD
0 Tc
[(that) -468 (a) -467 (relatively) -477 (stereot) -10.8999996185 (yped) -467.8999938965 (pattern) -469.299987793 (of) -467.5 (stru) -8.3999996185 (ctural) -465.799987793 (br) -7.5 (ain) ] TJ
0 -1.2264000177 TD
[(abno) -8.8999996185 (rmalities) -391.1000061035 (began) -383.8999938965 (to) -384.3999938965 (eme) -8.5 (rge.) -384.299987793 (T) 12.3000001907 (hese) -401.5 (changes) -387.1000061035 (include) -10.6999998093 (d) ] TJ
T*
[(cerebr) -9.6000003815 (al) -525.200012207 (atrop) -9.1000003815 (hy,) -529.5 (enlarg) -8.6000003815 (ement) -534.5 (of) -525.299987793 (the) -529.700012207 (late) -10.8000001907 (ral) -526.200012207 (and) -529.5 (third) ] TJ
ET
q
56.6930007935 147.1179962158 m
290.550994873 147.1179962158 l
290.550994873 93.9400024414 l
56.6930007935 93.9400024414 l
W
n
0 0 0 1 K
0.112999998 w
q
1 0 0 1 56.6930007935 147.0610046387 cm
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233.858001709 0 l
S
Q
Q
BT
/F3 1 Tf
7.4998998642 0 0 7.4998998642 56.6929016113 138.9542999268 Tm
0 0 0 rg
[(*) -265.1000061035 (Correspon) -13.8000001907 (dence:) ] TJ
0 0 0 1 k
7.7178997993 0 TD
[(amckee@b) -12.3000001907 (u.edu) ] TJ
5.6248002052 0 0 4.9991998672 56.6929016113 133.2850036621 Tm
0 0 0 rg
(1) Tj
7.4998998642 0 0 7.4998998642 59.3574981689 129.9402008057 Tm
[(VA) -307.8999938965 (Boston) -302.3999938965 (HealthCare) -308.1000061035 (System,) -300.3999938965 (150) -301.6000061035 (So) -8.8000001907 (uth) -302.3999938965 (Huntington) -306.5 (Avenue,) -302.3999938965 (Boston) ] TJ
-0.3553000093 -1.1943000555 TD
[(MA) -302.3999938965 (02130,) -303.8999938965 (USA) ] TJ
5.6248002052 0 0 4.9991998672 56.6929016113 115.3134002686 Tm
(3) Tj
7.4998998642 0 0 7.4998998642 59.3574981689 111.96849823 Tm
[(Departm) -13.1000003815 (ent) -298.1000061035 (of) -305.1000061035 (Pathology) -303.299987793 (and) -302.700012207 (Laboratory) -308.200012207 (Medicine) -13.1000003815 (,) -295.1000061035 (Boston) -302.3999938965 (Un) -8.1000003815 (iversity) ] TJ
-0.3553000093 -1.2019000053 TD
[(School) -304.8999938965 (of) -297.5 (M) -8.6000003815 (edicine,) -299.700012207 (72) -304.3999938965 (East) -303.700012207 (Concord) -302.6000061035 (Stree) -9.3000001907 (t,) -295.5 (Bosto) -9.5 (n,) -300.799987793 (MA) -302.3999938965 (02118,) -303.8999938965 (USA) ] TJ
T*
[(Full) -306.799987793 (list) -301.299987793 (of) -297.5 (author) -303.3999938965 (informa) -11.6999998093 (tion) -302.700012207 (is) -297.299987793 (available) -309.700012207 (at) -301.700012207 (the) -305.700012207 (end) -301 (of) -297.5 (the) -305.6000061035 (article) ] TJ
ET
/EmbeddedDocument /MC1 BDC
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368.5039978027 758.7210083008 170.0220031738 -36 re
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