IctusLe sequele epilettiche

Gaetano ZaccaraU.O. Neurologia, ASF Firenze

Firenze, 8 novembre 2014

Stroke emorragico: crisi immediate

F, 64 aa

Neurologìa ASF

TEA carot. Sn: 19 settembre 2007

Stroke: 24 settembre 2007Crisi: 24 settembre 2007

Mioclonìe emisoma Dx

Crisi immediate

• Si verificano generalmente all’esordio di una emorragia cerebrale

• Costituiscono il segno iniziale di uno stroke nel 4.8% dei casi

• Sono generalmente isolate e parziali• Le crisi elettrografiche sono 4 volte più

frequenti delle crisi cliniche

Stroke emorragico: crisi precoci

mioclonìe emivolto Dx fine crisi

F, 80 aa

Stroke : 14 settembre 2007Inizio crisi : 17 settembre 2007

EEG : 17 settembre 2007

Neurologìa ASF

Neurologìa ASF

Crisi sintomatiche acute

• Le crisi sintomatiche acute si osservano entro la prima settimana di un insulto cerebrale e non sono considerate espressione di epilessia.

• L’incidenza cumulativa delle crisi sintomatiche acute fino alla età di 80 anni di età è: 3.7%

• Queste crisi sono associate ad un aumento del rischio che dal danno neurologico possa originare una epilessia (Annegers et al., 1995)

Quali conseguenze hanno le crisi precoci nel paziente affetto da patologia

vascolare?

• Studi condotti sull’animale: aumento dell’area infartuale

• Tra i pazienti con ICH un maggiore deterioramento neurologico è stato osservato nei pazienti con crisi precoci (Vespa et al., 2003)

• Aumento della mortalità (Vernino et al 2003)

Crisi tardive

• Sono quelle crisi che insorgono dopo almeno 15 giorni dall’evento vascolare

• Si associano ad un maggior rischio di epilessia anzi ne costituiscono l’esordio

• Determinate da alterazioni strutturali della corteccia cerebrale (gliosi, cicatrice meningocerebrale, deafferentazione, perdita selettiva di neuroni, sprouting neuronale)

Epileptic Seizures and Epilepsy: Definitions Proposed by the International League Against

Epilepsy (ILAE) and the International Bureau for Epilepsy

Epilepsy is a disorder of the brain characterised by an enduring predisposition to generate epileptic seizures and by the neurobiologic, cognitive, psychological, and social consequences of this condition. The definition of epilepsy requires the occurrence of at least one epileptic seizure.

Fisher et al., Epilepsia 46:470-472, 2005

I dati epidemiologici

Neurology. 2011 Nov 15;77(20):1785-93.

Fattori di rischio delle crisi sintomatiche acute

• Emboli cardiogeni

• Lesioni molto estese • Interessamento della corteccia• Emorragia causata da trombosi delle

vene cerebrali

• Emorragia subaracnoidea • Sindrome da riperfusione • Ipoperfusione globale

Three thousand three-hundred ten patients with no history of epilepsy who presented with first stroke between 1995 and 2007. Mean follow-up: 3.8 yearsPSE incidence at 3 months and 1, 5, and 10 years were estimated at 1.5%, 3.5%, 9.0%, and 12.4%, respectively

Three thousand three-hundred ten patients with no history of epilepsy who presented with first stroke between 1995 and 2007

Terapia farmacologicaLa profilassi ed il trattamento delle

crisi sintomatiche acute

Seizures (epileptic attacks) after stroke are a major clinical problem. It is unclear whether antiepileptic drugs are effective in preventing seizures after stroke. This Cochrane review did not find any high quality clinical trials that have assessed whether antiepileptic drugs are more effective than placebo in preventing seizures after stroke. Currently, there is not enough evidence to justify the routine use of antiepileptic drugs to prevent seizures after stroke. Further research is needed for this important clinical problem.

Cochrane Database Syst Rev. 2014 Jan 24;1:CD005398

Sykes L, Wood E, Kwan J.

The prophylactic use of an antiepileptic drug in intracerebral hemorrhage

Results—157 patients met criteria for review. 46 (29%) patients were placed on a prophylactic AED. Eleven percent of patients placed on a prophylactic AED had an early seizure versus 6.3% who was not placed on a prophylactic AED. Interpretations— Patients with acute, spontaneous ICH are at an increased risk for early seizures. AED use is not significantly associated with the risk of early seizures, long-term epilepsy, disability, or death.

Objective— To evaluate whether patients presenting with acute, spontaneous intracerebral hemorrhage (ICH) benefit from prescription of prophylactic antiepileptic drugs (AEDs).

Redding et al., Clin Neurol Neurosurg. 2011 December ; 113(10): 895–897.

Seizures After Aneurysmal Subarachnoid Hemorrhage: A Systematic Review of Outcomes

Incidence of early seizure amongpatients treated for aneurysmal subarachnoid hemorrhage, by cohort.

Incidence of late seizure amongpatients treated for aneurysmal subarachnoid hemorrhage, by cohort.

Rapert et al., 2012 WORLD NEUROSURGERY

Twenty-five studies involving 7002 patients

Chumnanvej et al., Neurosurgery. 2007 60(1):99-102

Retrospective chart review on 269 patients , 85 of whom received prophylactic levetiracetam (n= 25) or phenytoin (n= 60). Glasgow Coma Scores at dismissal (median, 14 vs. 11, P = 0.023), and lower seizure incidence (0.0 vs. 8%, P = 0.03) was observed for patients receiving levetiracetam than for those treated withphenytoin. Also a trend was observed for a greater cognitive function retention rate (56.7% vs. 36%, P = 0.08) in patients treated with Levetiracetam.

LEV

PHT

Early seizures in cerebral vein and dural sinus thrombosis: risk factors and role

of antiepileptics.• METHODS: Multicenter, prospective, observational study. Analysis of risk factors

for seizures experienced before the diagnosis of CVT (presenting seizures) or within the following 2 weeks (early seizures).

• RESULTS: Two hundred forty-five of 624 (39.3%) patients with CVT experienced presenting seizures, and 43 (6.9%) patients had early seizure. In logistic-regression analysis, supratentorial lesion (OR=3.09, 95% CI=1.56 to 9.62) and presenting seizures (OR=1.74, 95% CI=0.90 to 3.37) predicted early seizures. The risk of early seizures in patients with supratentorial lesions and presenting seizures was significantly lower when AED prophylaxis was used (1 with seizures in 148 patients with AEDs vs 25 in 47 patients without AEDs; OR=0.006, 95% CI=0.001 to 0.05).

• CONCLUSIONS: Our results support the prescription of AEDs in acute CVT patients with supratentorial lesions who present with seizures.

Ferro et al., Stroke. 2008 Apr;39(4):1152-8.

Antiepileptic drugs for the primary and secondary prevention of seizures after intracranial venous thrombosis.

Price M, Günther A, Kwan JS Cochrane Database Syst Rev. 2014 Aug 2;8:CD005501.

MAIN RESULTS: No relevant studies were found.AUTHORS' CONCLUSIONS: There is no evidence to support or refute the use of antiepileptic drugs for the primary or secondary prevention of seizures related to intracranial venous thrombosis. Well-designed randomised controlled trials are urgently needed to inform practice.

Terapia farmacologicaIl trattamento dopo una prima crisi

sintomatica remota

Single Seizure - History

Evolution in thinking• Gowers (1881) - “seizures

beget seizures”• Current evidence:

– 60% of 1st seizures do not recur

– Delayed treatment does not influence outcome

Which information from RCTs?

Rowan et al Neurology 64: 1868-1873, 2005

Saetre et al., Epilepsia, 48:1292–1302, 2007

Brodie et al., Epilepsy Res. 37, 81–87, 1999

Retention analysis in studies performed in elderly patients with newly diagnosed epilepsies

Reduced plasma nisoldipine concentrations in phenytoin-treated patients with epilepsy.

Michelucci et al., 1996

Plasma nisoldipine concentration after a single oral dose of a controlled-release formulation of nisoldipine in 12 healthy controls and in 12 patients under treatment with phenytoin.

Nisoldipine dose was 40 mg in patients and 20 mg in controls.

We do not have a single drug for all clinical conditions

Comorbidity Suggested drugPatients with vascular diseases

lamotrigine, gabapentin, levetiracetam, zonisamide

Dementia with depression or apathy

Lamotrigine

Dementia with aggression valproate, gabapentin, oxcarbazepine

Brain tumor levetiracetam, valproate, topiramate, zonisamide

Substance abuse topiramateMigraine valproate, topiramate

Grazie per l’attenzione