La morte cerebrovascolare: può presentarsi come la

morte improvvisa cardiaca?

Giuseppe MicieliDip Neurologia d’Urgenza

IRCCS Istituto Neurologico Nazionale C MondinoPavia

Eleventh International SymposiumHeart Failure & Co.Morte Improvvisa

Reggia di Caserta 29-30 Aprile 2011

• After a stroke/TIA, patients are at high risk of short-term non-fatal stroke and of long-term fatal CHD• CHD is highly prevalent at autopsy in patients with stroke TIA• Recent studies confirm 10-year incidence of CHD in patients with stroke/TIA

is 20%• Secondary prevention should not only focus on the first 2-3 years• Long-term (4-5 years) secondary prevention trials (PROGRESS, SPARCL) show reduction in CHD events

Malattia cerebrovascolare: sottotipi di ictus

Albers GW et al. Chest. 1998;114:683S-698S.Rosamond WD et al. Stroke. 1999;30:736-743.

Ictus ischemico (83%)Ictus emorragico (17%)

Malattia aterotrombotica (20%)

Cardioembolismo (20%)

Patologia lacunare dei piccoli vasi (25%)

Criptogenetico e da cause rare(30%)

Emorragia intracranica (59%)

Emorragia subaracnoidea (41%)

– Mediche:• Cardiocircolatorie• Respiratorie• Infettive• Internistiche

– Neurologiche: • Stroke in evoluzione• Infarcimento emorragico• Ipertensione endocranica• Crisi epilettiche

Complicanze

Numbers and causes of death per week from stroke onset

Prosser J et al, Stroke 2007;38:2295-2302

4,5 hrs 16 hrs

TC cerebrale: ischemia cerebrale ed edema

30-day Case-Fatality Rate

Stroke type No. CFR 95%CI

Subarachnoid hemorrhage (n=118) 40 33.9% 25.4-42.4

Intracerebral hemorrhage (n=588) 284 48.3% 44.3-52.4

Cerebral ischemia (n=3594) 763 21.2% 19.9-22.5

Ill-defined events (n=53) 39 73.6% 61.7-85.5

Total (n=4353) 1126 25.9% 24.6-27.2

CFR: case-fatality rate, CI: confidence interval

L’Aquila Stroke Registry, 2004

Time interval qualifying sudden death (from symptoms)

• Up to 1 h Lie JT et al, 1975; Herzog CA et al, 2006

• Within 6 h Davies MJ et al, 1987; Corrado D et al, 1992

• Up to 24 h WHO , Sarkioja T et al, 1984; Siboni A et al, 1986

The day of the dead(1923-1924)Diego Rivera

Unexpected natural death among Korean workers (1994-1995)

Park J et al. J Occup Health 1999;41:238-243

Effects of cerebral lesions on the heart and blood pressure

Modified from Norris, 1983

64-year-old woman collapsed in the lobby of her apartment buildingCT-scan: right subdural hematoma with intracerebral right temporal and

insular hemorrhage

Baranchuk A et al. Cardiol J 2009;16:105-112

within 24 hours of admission

within 72 hours of admission

Brugada syndrome revealed by vertigo caused by cerebellar infarction (36-year-old man)

Denier C et al. Eur J Neurol 2010;17:e35-e36

Neurogenic T wave inversion in pure left stroke associated with hyperhomocysteinemia

Mandrioli J et al. JNNP 2003

admission7 days after the second stroke

Sudden cardiac arrest in a successfully embolized case of giant VA aneurysm with hydrocephalus

Mishra NK. Sur Neurol 2007;67:652-653

QT variability in CADASIL

Piccirillo G et al. Eur J Neurol 2008;15:1216-1221

Elettrocardiographic changes during central nervous system lesions

Baranchuk A et al. Cardiol J 2009;16:105-112

Neuroanatomic basis of stroke-related myocardial injury

Zhu et al, Neurology 2006

Stroke-induced sudden-autonomic death

• Role of the insular cortex in the pathophysiology of sudden death Oppenheimer et al, 1991

• Significant modulating effects of ventromedial prefrontal cortex (VMPFC) on cardiovascular responses to emotional stimuli Hiltz MJ et al. 2006

• Hemispheric dominance of sympathetic (RH) or parasympathetic (LH) activity Zamrini EY et al, 1990; Hiltz MJ et al, 2001

• Left-hemispheric inactivation increased sympathetic cardiovascular modulation; right-hemispheric inactivity furthered parasympathetic activity Hitz MJ et al, 2001

• Tailored resection of temporal lobe areas lowers sympathetic cardiovascular activation (shift towards cardiovagal predominance with possibile bradycardia or even asystole) Hiltz MJ et al 2006, Hiltz et al, 2001

Stroke-induced sudden-autonomic death

Predictors of cardiac death within 5 years after first ischemic stroke: multivariate analysis

Rincon F et al. Stroke 2008;39:2425-2431

• Infarction involving parietal lobe seem to be associated with an increased risk of cardiac events (HR 4.45 of cardiac death) Rincon et al, 2008

• Similar high risk of death after right parietal lobe infarction when infarct size is considered Rincon et al, 2008

• Probably, the parietal lobe has buffering effects on the insular region which are disinhibited after loss of parietal activity

Stroke-induced sudden-autonomic death

Cardiovascular Response after Insula Stimulation in Human Subjects

* significant difference compared with right anterior insula, p < 0.005** significant difference compared with right posterior insula, p < 0.005# significant difference compared with aggregate of right anterior and posterior insula, p < 0.005§ significant difference compared with left posterior insula, p < 0.005## significant difference compared with aggregate of left anterior and posterior insula, p < 0.005

Oppenheimer et al, 1992

Insular vs non insular involvement

Right vs Left insula

Atrial fibrillation 0.772 0.009

Sinus tachycardia HR>120 bpm

0.001 0.118

Sinus bradicardia HR<45 bpm 0.802 0.896

Atrioventricular block 0.969 0.029

Ectopic beats >10% 0.032 0.016

Prolonged QTc 0.470 0.736

ST depression 0.136 0.060

ST elevation 0.011 0.148

Inverted T wave 0.144 0.040

Isoform T wave 0.067 -

ECG abnormalities and insular involvement

Christensen et al, JNNP 2005 mod.

Two-year survival curves according to right-insular involvement

Abboud H et al, Ann Neurol 2006;59:691-699

ECG predictors for mortality among stroke cases with insular involvement

Abboud H et al, Ann Neurol 2006;59:691-699

Plasma norepinephrine concentration

Meyer S et al. Neuroreport 2004;15:357-361

Plasma epinephrine concentration

Meyer S et al. Neuroreport , 2004;15:357-361

Pathological Findings in the Heart of Patients with Brain Lesions

• Focal myocytolysis

• Myofibrillar degeneration

• Lipofuscin pigment deposition in myofibrils

• Hystocytic infiltration of the diffuse necrotic areas

Greenhoot and Reichenbach, 1969

Contraction band necrosis (coagulative myocytolysis, myofibrillar degeneration)

Fresh endocardial hemorrhage

The neurocardiac lesion: 30-year-old man died during an acute psychological stress

Intense mineralization within minutes of the onset of contraction band necrosis

Myocardial necrosis main patterns (Baroldi F, 1975): a) Coagulation necrosisb) Colliquative myocytolysisc) Coagulative myocytolysis (in reperfusion areas around regions of coagulation necrosis in transplanted heart, in sudden unexpected and accidental death, in hearts exposed to toxic levels of catecholamines)

Samuels MA. Circulation 2007;116:77-84

Cascade of events that lead to neurocardiac damage

Samuels MA, Circulation 2007;116:7784

Possible therapeutic approaches aimed to prevent neurocardiac damage

Samuels MA, Circulation 2007;116:7784