Ictus
Le sequele epilettiche
Gaetano Zaccara
U.O. Neurologia, ASF Firenze
Firenze, 8 novembre 2014
Stroke emorragico: crisi immediate
TEA carot. Sn: 19 settembre 2007
Stroke: 24 settembre 2007
Crisi: 24 settembre 2007
Neurologìa ASF
F, 64 aa
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
Stroke : 14 settembre 2007
Inizio crisi : 17 settembre 2007
EEG : 17 settembre 2007
Neurologìa ASF
F, 80 aa
Neurologìa ASF
mioclonìe emivolto Dx fine crisi
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 years
PSE 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 farmacologica
La profilassi ed il trattamento delle
crisi sintomatiche acute
Sykes L, Wood E, Kwan J.
Cochrane Database Syst Rev. 2014 Jan 24;1:CD005398
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.
The prophylactic use of an antiepileptic drug in
intracerebral hemorrhage
Objective— To evaluate whether patients presenting with
acute, spontaneous intracerebral hemorrhage (ICH) benefit
from prescription of prophylactic antiepileptic drugs (AEDs).
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.
Redding et al., Clin Neurol Neurosurg. 2011 December ; 113(10): 895–897.
Seizures After Aneurysmal Subarachnoid Hemorrhage:
A Systematic Review of Outcomes
Twenty-five studies involving 7002 patients
Incidence of early seizure among
patients treated for aneurysmal
subarachnoid hemorrhage, by cohort.
Incidence of late seizure among
patients treated for aneurysmal
subarachnoid hemorrhage, by cohort.
Rapert et al., 2012 WORLD NEUROSURGERY
Chumnanvej et al., Neurosurgery. 2007 60(1):99-102
LEV
PHT
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 with
phenytoin. Also a trend was observed for
a greater cognitive function retention rate
(56.7% vs. 36%, P = 0.08) in patients
treated with Levetiracetam.
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 logisticregression 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.
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.
Price M, Günther A, Kwan JS Cochrane Database Syst Rev. 2014 Aug 2;8:CD005501.
Terapia farmacologica
Il 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?
Retention analysis in studies performed in elderly
patients with newly diagnosed epilepsies
Brodie et al., Epilepsy Res. 37, 81–87, 1999
Rowan et al Neurology 64: 1868-1873, 2005
Saetre et al., Epilepsia, 48:1292–1302, 2007
Reduced plasma nisoldipine concentrations
in phenytoin-treated patients with epilepsy.
Nisoldipine dose was 40
mg in patients and 20 mg
in controls.
Plasma nisoldipine concentration after a single oral dose of a controlledrelease formulation of nisoldipine in 12 healthy controls and in 12
patients under treatment with phenytoin.
Michelucci et al., 1996
We do not have a single drug for all
clinical conditions
Comorbidity
Suggested drug
Patients with vascular
diseases
Dementia with depression
or apathy
Dementia with aggression
lamotrigine, gabapentin,
levetiracetam, zonisamide
Lamotrigine
Brain tumor
Substance abuse
Migraine
valproate, gabapentin,
oxcarbazepine
levetiracetam, valproate,
topiramate, zonisamide
topiramate
valproate, topiramate
Grazie per l’attenzione