Ictus Le sequele epilettiche Gaetano Zaccara U.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 2007 Crisi: 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 Dxfine crisi F, 80 aa Stroke : 14 settembre 2007 Inizio crisi : 17 settembre 2007 EEG : 17 settembre 2007 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: , 2005

I dati epidemiologici

Neurology Nov 15;77(20):

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 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

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 Jan 24;1:CD 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 December ; 113(10): 895–897.

Seizures After Aneurysmal Subarachnoid Hemorrhage: A Systematic Review of Outcomes 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 Twenty-five studies involving 7002 patients

Chumnanvej et al., Neurosurgery (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 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. 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 Apr;39(4):

Antiepileptic drugs for the primary and secondary prevention of seizures after intracranial venous thrombosis. Price M, Günther A, Kwan JS Cochrane Database Syst Rev Aug 2;8:CD 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 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? Rowan et al Neurology 64: , 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 ComorbiditySuggested drug Patients with vascular diseases lamotrigine, gabapentin, levetiracetam, zonisamide Dementia with depression or apathy Lamotrigine Dementia with aggressionvalproate, gabapentin, oxcarbazepine Brain tumorlevetiracetam, valproate, topiramate, zonisamide Substance abusetopiramate Migrainevalproate, topiramate

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