Autoimmunologiczna padaczka – Rokowania, prognozy i postęp choroby

Autoimmunologiczna padaczka
Rokowania, prognozy i postęp choroby

Autoimmunologiczna padaczka jest wynikiem procesów autoimmunologicznych, które prowadzą do napadów padaczkowych, a jej etiologia została uwzględniona w najnowszej klasyfikacji ILAE. Ryzyko rozwoju przewlekłej padaczki jest wyższe u pacjentów z przeciwciałami przeciwko antygenom wewnątrzkomórkowym (np. Hu, CV2/CRMP5, Ma2, GAD65), które są głównie paraneoplastyczne i mediowane przez komórki T, w porównaniu do przeciwciał przeciwko powierzchni neuronów (np. NMDAR, GABAbR, LGI1, CASPR2). Obecność tych ostatnich jest czynnikiem prognostycznym zmniejszającym ryzyko padaczki. Kluczowe znaczenie w prognozowaniu mają badania EEG, gdzie brak ogniskowego spowolnienia w ostrym EEG oraz obecność międzynapadowych wyładowań padaczkopodobnych (IEDs) lub wyładowań okresowych (PDs) w podostrej fazie (3-12 miesięcy) są niezależnymi predyktorami rozwoju lekoopornej padaczki poencelafitycznej. Młodszy wiek w momencie zachorowania oraz opóźnione rozpoczęcie immunoterapii (po 3 miesiącach od wystąpienia objawów) zwiększają ryzyko przewlekłej padaczki (OR 4,16, CI 1,11-16,30). W badaniach obserwacyjnych około 29,2% pacjentów rozwija lekooporną padaczkę poencelafityczną po średnim czasie obserwacji 4,9 lat.

Wprowadzenie do autoimmunologicznej padaczki (Autoimmunologiczna padaczka)
Czynniki prognostyczne w autoimmunologicznej padaczce

Rola typów przeciwciał w prognozowaniu
Znaczenie badań elektroencefalograficznych (EEG) w prognozowaniu
Wiek i czas rozpoczęcia leczenia
Inne czynniki predykcyjne

Modele predykcyjne w diagnostyce i leczeniu autoimmunologicznej padaczki

Długoterminowe wyniki w padaczce autoimmunologicznej
Obserwacje długookresowe

Wskaźniki śmiertelności i nawrotów
Następstwa długookresowe

Wpływ na funkcje poznawcze

Znaczenie wczesnej immunoterapii
Podsumowanie prognozy w autoimmunologicznej padaczce

Kolejne rozdziały

Wprowadzenie do autoimmunologicznej padaczki (Autoimmunologiczna padaczka)

Autoimmunologiczna padaczka to stan chorobowy, w którym napady padaczkowe są spowodowane lub związane z procesami autoimmunologicznymi. Najnowsza klasyfikacja Międzynarodowej Ligi Przeciwpadaczkowej (ILAE) uwzględnia „etiologię immunologiczną” jako jedną z przyczyn padaczki, obok innych dobrze znanych przyczyn.¹ Chociaż większość przypadków autoimmunologicznego zapalenia mózgu (AE) przebiega z napadami padaczkowymi, tylko mniejszość z nich ewoluuje do długotrwałej padaczki.²

Czynniki prognostyczne w autoimmunologicznej padaczce

Rola typów przeciwciał w prognozowaniu

Ryzyko rozwoju padaczki jest wyższe u pacjentów z przeciwciałami skierowanymi przeciwko antygenom wewnątrzkomórkowym (mediowane przez komórki T i głównie paraneoplastyczne, takie jak przeciwciała Hu, CV2/CRMP5, Ma2, GAD65) w porównaniu z pacjentami z przeciwciałami przeciwko powierzchni neuronów (mediowane przez przeciwciała i rzadziej paraneoplastyczne, takie jak przeciwciała NMDAR, GABAbR, LGI1, CASPR2).³ Obecność przeciwciał przeciwko powierzchni komórek jest czynnikiem prognostycznym zmniejszającym ryzyko rozwoju padaczki.⁴

Obserwacje kliniczne potwierdzają, że pacjenci z nieparaneoplastycznym autoimmunologicznym zapaleniem mózgu mają korzystniejsze rokowanie. W badaniach odnotowano korzystny wynik dla wszystkich pacjentów z przeciwciałami anty-CASPR2 i jednego pacjenta z przeciwciałami anty-LGI1 (mRS = 0), podczas gdy wyniki w paraneoplastycznym AE i podejrzewanym AE były gorsze (mRS = 0 tylko u dwóch pacjentów).⁵⁶

Znaczenie badań elektroencefalograficznych (EEG) w prognozowaniu

Wyniki badań EEG odgrywają kluczową rolę w prognozowaniu rozwoju padaczki poencelafitycznej. Niezależnymi czynnikami predykcyjnymi rozwoju padaczki są:⁷

Brak ogniskowego spowolnienia w ostrym EEG
Obecność międzynapadowych wyładowań padaczkopodobnych (IEDs) lub wyładowań okresowych (PDs) w podostrej fazie EEG (3-12 miesięcy po wystąpieniu objawów)⁸

Zidentyfikowane czynniki prognostyczne są istotne dla klinicznego przewidywania ryzyka rozwoju lekoopornej padaczki poencelafitycznej, która występuje u około jednej trzeciej pacjentów z AE i ostrymi napadami.⁹

Wiek i czas rozpoczęcia leczenia

Młodszy wiek w momencie wystąpienia choroby jest predyktorem rozwoju długotrwałej padaczki.¹⁰ Dodatkowo, opóźnione rozpoczęcie immunoterapii zwiększa ryzyko rozwoju padaczki.¹¹ Pacjenci z autoimmunologiczną padaczką są zazwyczaj młodsi w porównaniu do pacjentów z padaczką o innej etiologii (p = 0,028).¹²

Immunoterapia zastosowana w ciągu trzech miesięcy od wystąpienia objawów wiąże się ze zmniejszonym ryzykiem rozwoju padaczki u pacjentów z przeciwciałami neuralnymi (OR 4,16, CI 1,11-16,30).¹³ Późne napady padaczkowe w nieparaneoplastycznym AE znane są z korzystnego rokowania, co potwierdza wysoki odsetek pacjentów wolnych od napadów po zastosowaniu przynajmniej jednego leku przeciwpadaczkowego (ASD) i/lub immunoterapii (IT).¹⁴

Inne czynniki predykcyjne

W porównaniu z pacjentami bez potwierdzonego AE, pacjenci z pewnym lub podejrzewanym AE:¹⁵

Częściej mają historię lub aktywną chorobę nowotworową (p = 0,006)
Wykazują specyficzne przyśrodkowe skroniowe deficyty neuropsychologiczne (p = 0,0012)
Częściej mają podwyższoną liczbę komórek w płynie mózgowo-rdzeniowym >4/μl (p = 0,0002)
Częściej występują izolowane prążki oligoklonalne (OCB) w płynie mózgowo-rdzeniowym (p = 0,0012)
Prezentują jednostronne przyśrodkowe skroniowe hiperintensywności w obrazie T2 w badaniu MRI (p = 0,0001)

Do czynników predykcyjnych długotrwałej padaczki należą również epizody opornego stanu padaczkowego (refractory status epilepticus).¹⁶

Modele predykcyjne w diagnostyce i leczeniu autoimmunologicznej padaczki

W diagnostyce i leczeniu autoimmunologicznej padaczki wykorzystuje się modele predykcyjne, które pomagają w identyfikacji pacjentów z obecnością przeciwciał neuronalnych i potencjalną odpowiedzią na immunoterapię. Skale APE (Autoimmune Epilepsy) i RITE (Response to Immunotherapy in Epilepsy) mogą wspomagać diagnozę, leczenie i prognozowanie autoimmunologicznej padaczki.¹⁷

Długoterminowe wyniki w padaczce autoimmunologicznej

Mimo wysokiej częstości napadów padaczkowych i skłonności do rozwoju stanu padaczkowego (SE) w ostrej fazie autoimmunologicznego zapalenia mózgu, większość pacjentów z AE nie rozwija trwałej predyspozycji do napadów w perspektywie długoterminowej.¹⁸ Ta obserwacja uzasadnia stopniowe odstawianie leków przeciwpadaczkowych po ostrej fazie u większości pacjentów wolnych od napadów, u których nie stwierdza się wyładowań padaczkopodobnych w badaniach EEG.¹⁹

Według niedawnego wieloośrodkowego włoskiego badania obejmującego 263 pacjentów z napadami związanymi z AE, 43,7% przypadków rozwinęło przewlekłą padaczkę w długoterminowej obserwacji.²⁰ Wskazuje to, że większość pacjentów z AE rozwija ostre objawowe napady padaczkowe, w tym przypadki SE i opornego SE (RSE), ale tylko mniejszość z nich przejdzie do autoimmunologicznej padaczki, szczególnie pacjenci z przeciwciałami onkoneuralnymi (paraneoplastycznymi) oraz przeciwciałami GAD65.²¹

Obserwacje długookresowe

W badaniu obserwacyjnym pacjentów z autoimmunologicznym zapaleniem mózgu, po średnim okresie obserwacji wynoszącym 4,9 lat, u 29,2% rozwinęła się lekooporna padaczka poencelafityczna.²² W innym badaniu follow-up przeprowadzono u 59% (n = 10/17) pacjentów z pewnym lub podejrzewanym AE, ze średnim czasem obserwacji 40 miesięcy (zakres: 6-102) po pierwszym napadzie padaczkowym. Wśród pacjentów objętych obserwacją, wszyscy byli wolni od napadów podczas ostatniej wizyty kontrolnej, trzech z nich przy zastosowaniu pierwszego użytego leku przeciwpadaczkowego.²³

Przy przyjęciu do szpitala wskaźnik mRS był niski (≤2) u większości pacjentów z pewnym lub podejrzewanym AE (n = 12/17, 71%), zmniejszając się do 60% (n = 6/10) podczas ostatniej wizyty kontrolnej.²⁴

Wskaźniki śmiertelności i nawrotów

W autoimmunologicznym zapaleniu mózgu wskaźnik śmiertelności waha się od 6% do 19%, podczas gdy ryzyko nawrotu wynosi 10-38%, z wyjątkiem dwóch serii przypadków: jednej dotyczącej zapalenia mózgu LGI-1, która wykazała wskaźnik nawrotu 52%, i jednej dotyczącej pacjentów z zapaleniem mózgu MOG, u których wskaźnik ten wynosił 62%.²⁵

Termin FLAMES (FLAIR-hyperintense Lesions in anti-MOG associated encephalitis with seizures) został użyty do opisania zapalenia mózgu u niektórych pacjentów z przeciwciałami MOG. Obraz kliniczny obejmuje napady padaczkowe związane z izolowanymi lub przeważnie jednostronnymi korowymi hiperintensywnymi zmianami w obrazach FLAIR MRI.²⁶

Następstwa długookresowe

Na podstawie skali mRS, większość pacjentów z autoimmunologicznym zapaleniem mózgu miała dobre wyniki. Jednak badania mierzące dogłębnie funkcje poznawcze, psychiatryczne lub wyniki zgłaszane przez pacjentów wykazały, że utrzymujące się upośledzenia są powszechne, szczególnie w zakresie pamięci, uwagi, funkcji wykonawczych i szybkości przetwarzania.²⁷

Trwałe upośledzenia są powszechne wśród osób, które przeżyły autoimmunologiczne zapalenie mózgu, potrzebne są dodatkowe badania, aby lepiej zrozumieć charakter i wpływ tych następstw.²⁸ Kompleksowe i bardziej jednolite podejście do oceny pacjentów wychodzących z zapalenia mózgu, wykorzystujące zwalidowane instrumenty w rutynowych odstępach czasu w celu uchwycenia wymiarów potencjalnych utrzymujących się objawów i następstw, jest kluczowe dla zrozumienia wyników po zapaleniu mózgu.²⁹

Wpływ na funkcje poznawcze

Pacjenci z autoimmunologicznym zapaleniem mózgu mogą doświadczać deficytów poznawczych, szczególnie w kontekście uszkodzenia hipokampa, co jest istotne w kontekście zapalenia mózgu związanego z przeciwciałami LGI1. Ocena deficytów poznawczych i strukturalnych uszkodzeń hipokampa w zapaleniu mózgu z przeciwciałami przeciwko białku LGI1 (leucine-rich, glioma-inactivated 1) jest istotnym elementem długoterminowej oceny prognostycznej.³⁰

Znaczenie wczesnej immunoterapii

Wczesna immunoterapia ma kluczowe znaczenie w poprawie rokowania u pacjentów z autoimmunologiczną padaczką. Szczególnie ważna jest u pacjentów z napadami dystonicznymi twarzowo-brachialnymi (faciobrachial dystonic seizures), które są charakterystyczne dla zapalenia mózgu związanego z przeciwciałami LGI1.³¹

Napady padaczkowe są powszechne we wszystkich typach autoimmunologicznego zapalenia mózgu, ale ich częstość i ciężkość są szczególnie istotne w zapaleniu mózgu anty-NMDAR, anty-GABAbR, anty-GABAaR i anty-LGI.³² Tylko niewielka liczba pacjentów z zapaleniem mózgu anty-NMDAR lub anty-GABAbR prezentuje się jako NORSE (New-Onset Refractory Status Epilepticus).³³

Podsumowanie prognozy w autoimmunologicznej padaczce

Prognoza w autoimmunologicznej padaczce zależy od wielu czynników, w tym typu przeciwciał, czasu rozpoczęcia leczenia, wyników badań EEG oraz wieku pacjenta w momencie wystąpienia choroby. Pacjenci z nieparaneoplastycznym AE i przeciwciałami przeciwko powierzchni komórek mają lepsze rokowanie niż pacjenci z paraneoplastycznym AE i przeciwciałami przeciwko antygenom wewnątrzkomórkowym.³⁴³⁵

Wczesna immunoterapia jest kluczowym czynnikiem poprawiającym rokowanie, a około jedna trzecia pacjentów z AE i ostrymi napadami rozwija lekooporną padaczkę poencelafityczną.³⁶ Modele predykcyjne, takie jak skale APE i RITE, mogą pomóc w diagnozowaniu, leczeniu i prognozowaniu autoimmunologicznej padaczki.³⁷

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Materiały źródłowe

#1 Seizures, Epilepsy, and NORSE Secondary to Autoimmune Encephalitis: A Practical Guide for Clinicians
https://www.mdpi.com/2227-9059/11/1/44
The most recent International League Against Epilepsy (ILAE) classification has included âimmune etiologyâ along with other well-known causes of epilepsy. […] Most autoimmune encephalitides (AE) present with seizures, but only a minority of cases evolve to long-term epilepsy. […] The risk of epilepsy is higher for patients harboring Abs targeting intracellular antigens (T cell-mediated and mostly paraneoplastic, such as Hu, CV2/CRMP5, Ma2, GAD65 Abs), compared with patients with neuronal surface Abs (antibody-mediated and less frequently paraneoplastic, such as NMDAR, GABAbR, LGI1, CASPR2 Abs). […] Despite the high frequency of seizures and propensity to develop status epilepticus (SE) in the acute stage of autoimmune encephalitis (AE), most patients with AE do not develop an enduring predisposition to seizures over the long-term.
#2 Seizures, Epilepsy, and NORSE Secondary to Autoimmune Encephalitis: A Practical Guide for Clinicians
https://www.mdpi.com/2227-9059/11/1/44
The most recent International League Against Epilepsy (ILAE) classification has included âimmune etiologyâ along with other well-known causes of epilepsy. […] Most autoimmune encephalitides (AE) present with seizures, but only a minority of cases evolve to long-term epilepsy. […] The risk of epilepsy is higher for patients harboring Abs targeting intracellular antigens (T cell-mediated and mostly paraneoplastic, such as Hu, CV2/CRMP5, Ma2, GAD65 Abs), compared with patients with neuronal surface Abs (antibody-mediated and less frequently paraneoplastic, such as NMDAR, GABAbR, LGI1, CASPR2 Abs). […] Despite the high frequency of seizures and propensity to develop status epilepticus (SE) in the acute stage of autoimmune encephalitis (AE), most patients with AE do not develop an enduring predisposition to seizures over the long-term.
#3 Seizures, Epilepsy, and NORSE Secondary to Autoimmune Encephalitis: A Practical Guide for Clinicians
https://www.mdpi.com/2227-9059/11/1/44
The most recent International League Against Epilepsy (ILAE) classification has included âimmune etiologyâ along with other well-known causes of epilepsy. […] Most autoimmune encephalitides (AE) present with seizures, but only a minority of cases evolve to long-term epilepsy. […] The risk of epilepsy is higher for patients harboring Abs targeting intracellular antigens (T cell-mediated and mostly paraneoplastic, such as Hu, CV2/CRMP5, Ma2, GAD65 Abs), compared with patients with neuronal surface Abs (antibody-mediated and less frequently paraneoplastic, such as NMDAR, GABAbR, LGI1, CASPR2 Abs). […] Despite the high frequency of seizures and propensity to develop status epilepticus (SE) in the acute stage of autoimmune encephalitis (AE), most patients with AE do not develop an enduring predisposition to seizures over the long-term.
#4 Long-Term Seizure Outcomes in Autoimmune Encephalitis
https://pmc.ncbi.nlm.nih.gov/articles/PMC11962926/
Seizures are common in autoimmune encephalitis (AE), but identifying patients at risk of chronic epilepsy in the post-acute phase remains challenging. This study aims to identify risk factors of treatment-resistant postencephalitic epilepsy. […] Over a median follow-up of 4.9 years, 29.2% developed treatment-resistant postencephalitic epilepsy. Independent predictors of postencephalitic epilepsy included focal slowing on acute EEG (OR 0.15, CI 0.02-0.90), interictal epileptiform discharges (IEDs) or periodic discharges (PDs) on subacute EEG (OR 20.01, CI 1.94-206.44), and cell surface antibodies (OR 0.21, CI 0.05-0.89). Immunotherapy within three months of onset was associated with decreased epilepsy development in patients with neural antibodies (OR 4.16, CI 1.11-16.30). […] Nearly one-third of patients with AE and acute seizures developed treatment-resistant postencephalitic epilepsy, with significant predictors including absence of focal slowing on acute EEG, presence of IEDs and PDs on subacute EEG, absence of cell surface antibodies, and absence of early immunotherapy treatment of patients with positive neural antibodies.
#5 Frontiers | Autoimmune Encephalitis in Late-Onset Seizures: When to Suspect and How to Treat
https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2021.633999/full
A follow-up (FU) was carried out in 59% (n = 10/17) of patients with dAE or sAE, with a mean FU time of 40 months (range: 6â102) after the first seizure disorder. Of the remaining seven patients, five (29%) were lost to follow-up (three patients with dAE, two patients with sAE), and two had a follow-up of <6 months. Among those with FU, all were seizure-free at last FU, three of them with the first used ASD. [...] At hospital admission mRS was low (â¤2) in the majority of dAE/sAE patients (n = 12/17, 71%), decreasing to a proportion of 60% (n = 6/10) at last FU. Outcome was favorable for non-paraneoplastic AE (mRS = 0 for all patients with anti-CASPR2 AB and the one patient with anti-LGI1 AB); outcomes in paraneoplastic AE and suspected AE, however, were worse (mRS = 0 in only two patients).
#6 Frontiers | Autoimmune Encephalitis in Late-Onset Seizures: When to Suspect and How to Treat
https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2021.633999/full
Late-onset seizures in non-paraneoplastic AE are known to have a favorable prognosis, corresponding to our findings with a high seizure-free rate with at least one ASD and/or IT. Overall impairment at hospital admission was low (47% mRS 0, 71% mRS â¤2), probably due to the high rate of anti-CASPR2 AB AE (24%) in our patient cohort.
#7 Long-Term Seizure Outcomes in Autoimmune Encephalitis
https://pmc.ncbi.nlm.nih.gov/articles/PMC11962926/
Seizures are common in autoimmune encephalitis (AE), but identifying patients at risk of chronic epilepsy in the post-acute phase remains challenging. This study aims to identify risk factors of treatment-resistant postencephalitic epilepsy. […] Over a median follow-up of 4.9 years, 29.2% developed treatment-resistant postencephalitic epilepsy. Independent predictors of postencephalitic epilepsy included focal slowing on acute EEG (OR 0.15, CI 0.02-0.90), interictal epileptiform discharges (IEDs) or periodic discharges (PDs) on subacute EEG (OR 20.01, CI 1.94-206.44), and cell surface antibodies (OR 0.21, CI 0.05-0.89). Immunotherapy within three months of onset was associated with decreased epilepsy development in patients with neural antibodies (OR 4.16, CI 1.11-16.30). […] Nearly one-third of patients with AE and acute seizures developed treatment-resistant postencephalitic epilepsy, with significant predictors including absence of focal slowing on acute EEG, presence of IEDs and PDs on subacute EEG, absence of cell surface antibodies, and absence of early immunotherapy treatment of patients with positive neural antibodies.
#8 Long-Term Seizure Outcomes in Autoimmune Encephalitis
https://pmc.ncbi.nlm.nih.gov/articles/PMC11962926/
IEDs or PDs on EEGs obtained between 3 to 12 months after symptom onset were found to be independent predictors for the development of epilepsy, while focal slowing on EEGs obtained during the acute phase of AE and cell surface antibodies were found to be predictors against the development of epilepsy.
#9 Long-Term Seizure Outcomes in Autoimmune Encephalitis
https://pmc.ncbi.nlm.nih.gov/articles/PMC11962926/
Seizures are common in autoimmune encephalitis (AE), but identifying patients at risk of chronic epilepsy in the post-acute phase remains challenging. This study aims to identify risk factors of treatment-resistant postencephalitic epilepsy. […] Over a median follow-up of 4.9 years, 29.2% developed treatment-resistant postencephalitic epilepsy. Independent predictors of postencephalitic epilepsy included focal slowing on acute EEG (OR 0.15, CI 0.02-0.90), interictal epileptiform discharges (IEDs) or periodic discharges (PDs) on subacute EEG (OR 20.01, CI 1.94-206.44), and cell surface antibodies (OR 0.21, CI 0.05-0.89). Immunotherapy within three months of onset was associated with decreased epilepsy development in patients with neural antibodies (OR 4.16, CI 1.11-16.30). […] Nearly one-third of patients with AE and acute seizures developed treatment-resistant postencephalitic epilepsy, with significant predictors including absence of focal slowing on acute EEG, presence of IEDs and PDs on subacute EEG, absence of cell surface antibodies, and absence of early immunotherapy treatment of patients with positive neural antibodies.
#10 Seizures, Epilepsy, and NORSE Secondary to Autoimmune Encephalitis: A Practical Guide for Clinicians
https://www.mdpi.com/2227-9059/11/1/44
The aim of this review is to provide a comprehensive and practical overview on diagnosis and management of immune-mediated seizures and epilepsy. […] The majority of patients with acute symptomatic seizures secondary to AE do not develop autoimmune-associated epilepsy, justifying gradual ASMs tapering after the acute phase in most seizure-free patients lacking epileptic discharges on EEG examinations. […] In a recent multicenter Italian study involving 263 patients with AE-related seizures, 43.7% of cases developed chronic epilepsy on long-term follow-up. […] The predictors of long-term epilepsy were younger age at disease onset, the detection of intracellular (onconeural or GAD65) Abs and episodes of refractory SE as well as delay in immunotherapy initiation. […] Most patients with AE develop acute symptomatic seizures, including cases of SE and RSE. A minority of them will evolve to an autoimmune-associated epilepsy, especially those with onconeural (paraneoplastic) Abs, as well as those with GAD65 Abs.
#11 Seizures, Epilepsy, and NORSE Secondary to Autoimmune Encephalitis: A Practical Guide for Clinicians
https://www.mdpi.com/2227-9059/11/1/44
The aim of this review is to provide a comprehensive and practical overview on diagnosis and management of immune-mediated seizures and epilepsy. […] The majority of patients with acute symptomatic seizures secondary to AE do not develop autoimmune-associated epilepsy, justifying gradual ASMs tapering after the acute phase in most seizure-free patients lacking epileptic discharges on EEG examinations. […] In a recent multicenter Italian study involving 263 patients with AE-related seizures, 43.7% of cases developed chronic epilepsy on long-term follow-up. […] The predictors of long-term epilepsy were younger age at disease onset, the detection of intracellular (onconeural or GAD65) Abs and episodes of refractory SE as well as delay in immunotherapy initiation. […] Most patients with AE develop acute symptomatic seizures, including cases of SE and RSE. A minority of them will evolve to an autoimmune-associated epilepsy, especially those with onconeural (paraneoplastic) Abs, as well as those with GAD65 Abs.
#12 Frontiers | Autoimmune Encephalitis in Late-Onset Seizures: When to Suspect and How to Treat
https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2021.633999/full
Objective: This study was conducted to elucidate prevalence, clinical features, outcomes, and best treatment in patients with late-onset seizures due to autoimmune encephalitis (AE). […] Significance: AE is an important etiology in late-onset seizures, and seizures may be the first symptom of AE. Outcome in non-paraneoplastic AE was favorable with ASD and IT. […] Compared with patients with no evidence of AE, those with definite and suspected AE (dAE/sAE) (i) were significantly younger (p = 0.028), (ii) more frequently presented with a history of/or an active tumor disease (p = 0.006), (iii) showed specific mesial temporal neuropsychological deficits (p = 0.0012), (iv) more frequently elevated CSF cell counts >4/Î¼l (p = 0.0002) and isolated OCB (p = 0.0012) in CSF, and (v) unilateral mesial temporal T2-hyperintensities in MRI (p = 0.0001).
#13 Long-Term Seizure Outcomes in Autoimmune Encephalitis
https://pmc.ncbi.nlm.nih.gov/articles/PMC11962926/
Seizures are common in autoimmune encephalitis (AE), but identifying patients at risk of chronic epilepsy in the post-acute phase remains challenging. This study aims to identify risk factors of treatment-resistant postencephalitic epilepsy. […] Over a median follow-up of 4.9 years, 29.2% developed treatment-resistant postencephalitic epilepsy. Independent predictors of postencephalitic epilepsy included focal slowing on acute EEG (OR 0.15, CI 0.02-0.90), interictal epileptiform discharges (IEDs) or periodic discharges (PDs) on subacute EEG (OR 20.01, CI 1.94-206.44), and cell surface antibodies (OR 0.21, CI 0.05-0.89). Immunotherapy within three months of onset was associated with decreased epilepsy development in patients with neural antibodies (OR 4.16, CI 1.11-16.30). […] Nearly one-third of patients with AE and acute seizures developed treatment-resistant postencephalitic epilepsy, with significant predictors including absence of focal slowing on acute EEG, presence of IEDs and PDs on subacute EEG, absence of cell surface antibodies, and absence of early immunotherapy treatment of patients with positive neural antibodies.
#14 Frontiers | Autoimmune Encephalitis in Late-Onset Seizures: When to Suspect and How to Treat
https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2021.633999/full
Late-onset seizures in non-paraneoplastic AE are known to have a favorable prognosis, corresponding to our findings with a high seizure-free rate with at least one ASD and/or IT. Overall impairment at hospital admission was low (47% mRS 0, 71% mRS â¤2), probably due to the high rate of anti-CASPR2 AB AE (24%) in our patient cohort.
#15 Frontiers | Autoimmune Encephalitis in Late-Onset Seizures: When to Suspect and How to Treat
https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2021.633999/full
Objective: This study was conducted to elucidate prevalence, clinical features, outcomes, and best treatment in patients with late-onset seizures due to autoimmune encephalitis (AE). […] Significance: AE is an important etiology in late-onset seizures, and seizures may be the first symptom of AE. Outcome in non-paraneoplastic AE was favorable with ASD and IT. […] Compared with patients with no evidence of AE, those with definite and suspected AE (dAE/sAE) (i) were significantly younger (p = 0.028), (ii) more frequently presented with a history of/or an active tumor disease (p = 0.006), (iii) showed specific mesial temporal neuropsychological deficits (p = 0.0012), (iv) more frequently elevated CSF cell counts >4/Î¼l (p = 0.0002) and isolated OCB (p = 0.0012) in CSF, and (v) unilateral mesial temporal T2-hyperintensities in MRI (p = 0.0001).
#16 Seizures, Epilepsy, and NORSE Secondary to Autoimmune Encephalitis: A Practical Guide for Clinicians
https://www.mdpi.com/2227-9059/11/1/44
The aim of this review is to provide a comprehensive and practical overview on diagnosis and management of immune-mediated seizures and epilepsy. […] The majority of patients with acute symptomatic seizures secondary to AE do not develop autoimmune-associated epilepsy, justifying gradual ASMs tapering after the acute phase in most seizure-free patients lacking epileptic discharges on EEG examinations. […] In a recent multicenter Italian study involving 263 patients with AE-related seizures, 43.7% of cases developed chronic epilepsy on long-term follow-up. […] The predictors of long-term epilepsy were younger age at disease onset, the detection of intracellular (onconeural or GAD65) Abs and episodes of refractory SE as well as delay in immunotherapy initiation. […] Most patients with AE develop acute symptomatic seizures, including cases of SE and RSE. A minority of them will evolve to an autoimmune-associated epilepsy, especially those with onconeural (paraneoplastic) Abs, as well as those with GAD65 Abs.
#17 Predictive models in the diagnosis and treatment of autoimmune epilepsy – PubMed
https://pubmed.ncbi.nlm.nih.gov/28555833/
Objective: To validate predictive models for neural antibody positivity and immunotherapy response in epilepsy. […] APE and RITE scores can aid diagnosis, treatment, and prognostication of autoimmune epilepsy.
#18 Seizures, Epilepsy, and NORSE Secondary to Autoimmune Encephalitis: A Practical Guide for Clinicians
https://www.mdpi.com/2227-9059/11/1/44
The most recent International League Against Epilepsy (ILAE) classification has included âimmune etiologyâ along with other well-known causes of epilepsy. […] Most autoimmune encephalitides (AE) present with seizures, but only a minority of cases evolve to long-term epilepsy. […] The risk of epilepsy is higher for patients harboring Abs targeting intracellular antigens (T cell-mediated and mostly paraneoplastic, such as Hu, CV2/CRMP5, Ma2, GAD65 Abs), compared with patients with neuronal surface Abs (antibody-mediated and less frequently paraneoplastic, such as NMDAR, GABAbR, LGI1, CASPR2 Abs). […] Despite the high frequency of seizures and propensity to develop status epilepticus (SE) in the acute stage of autoimmune encephalitis (AE), most patients with AE do not develop an enduring predisposition to seizures over the long-term.
#19 Seizures, Epilepsy, and NORSE Secondary to Autoimmune Encephalitis: A Practical Guide for Clinicians
https://www.mdpi.com/2227-9059/11/1/44
The aim of this review is to provide a comprehensive and practical overview on diagnosis and management of immune-mediated seizures and epilepsy. […] The majority of patients with acute symptomatic seizures secondary to AE do not develop autoimmune-associated epilepsy, justifying gradual ASMs tapering after the acute phase in most seizure-free patients lacking epileptic discharges on EEG examinations. […] In a recent multicenter Italian study involving 263 patients with AE-related seizures, 43.7% of cases developed chronic epilepsy on long-term follow-up. […] The predictors of long-term epilepsy were younger age at disease onset, the detection of intracellular (onconeural or GAD65) Abs and episodes of refractory SE as well as delay in immunotherapy initiation. […] Most patients with AE develop acute symptomatic seizures, including cases of SE and RSE. A minority of them will evolve to an autoimmune-associated epilepsy, especially those with onconeural (paraneoplastic) Abs, as well as those with GAD65 Abs.
#20 Seizures, Epilepsy, and NORSE Secondary to Autoimmune Encephalitis: A Practical Guide for Clinicians
https://www.mdpi.com/2227-9059/11/1/44
The aim of this review is to provide a comprehensive and practical overview on diagnosis and management of immune-mediated seizures and epilepsy. […] The majority of patients with acute symptomatic seizures secondary to AE do not develop autoimmune-associated epilepsy, justifying gradual ASMs tapering after the acute phase in most seizure-free patients lacking epileptic discharges on EEG examinations. […] In a recent multicenter Italian study involving 263 patients with AE-related seizures, 43.7% of cases developed chronic epilepsy on long-term follow-up. […] The predictors of long-term epilepsy were younger age at disease onset, the detection of intracellular (onconeural or GAD65) Abs and episodes of refractory SE as well as delay in immunotherapy initiation. […] Most patients with AE develop acute symptomatic seizures, including cases of SE and RSE. A minority of them will evolve to an autoimmune-associated epilepsy, especially those with onconeural (paraneoplastic) Abs, as well as those with GAD65 Abs.
#21 Seizures, Epilepsy, and NORSE Secondary to Autoimmune Encephalitis: A Practical Guide for Clinicians
https://www.mdpi.com/2227-9059/11/1/44
The aim of this review is to provide a comprehensive and practical overview on diagnosis and management of immune-mediated seizures and epilepsy. […] The majority of patients with acute symptomatic seizures secondary to AE do not develop autoimmune-associated epilepsy, justifying gradual ASMs tapering after the acute phase in most seizure-free patients lacking epileptic discharges on EEG examinations. […] In a recent multicenter Italian study involving 263 patients with AE-related seizures, 43.7% of cases developed chronic epilepsy on long-term follow-up. […] The predictors of long-term epilepsy were younger age at disease onset, the detection of intracellular (onconeural or GAD65) Abs and episodes of refractory SE as well as delay in immunotherapy initiation. […] Most patients with AE develop acute symptomatic seizures, including cases of SE and RSE. A minority of them will evolve to an autoimmune-associated epilepsy, especially those with onconeural (paraneoplastic) Abs, as well as those with GAD65 Abs.
#22 Long-Term Seizure Outcomes in Autoimmune Encephalitis
https://pmc.ncbi.nlm.nih.gov/articles/PMC11962926/
Seizures are common in autoimmune encephalitis (AE), but identifying patients at risk of chronic epilepsy in the post-acute phase remains challenging. This study aims to identify risk factors of treatment-resistant postencephalitic epilepsy. […] Over a median follow-up of 4.9 years, 29.2% developed treatment-resistant postencephalitic epilepsy. Independent predictors of postencephalitic epilepsy included focal slowing on acute EEG (OR 0.15, CI 0.02-0.90), interictal epileptiform discharges (IEDs) or periodic discharges (PDs) on subacute EEG (OR 20.01, CI 1.94-206.44), and cell surface antibodies (OR 0.21, CI 0.05-0.89). Immunotherapy within three months of onset was associated with decreased epilepsy development in patients with neural antibodies (OR 4.16, CI 1.11-16.30). […] Nearly one-third of patients with AE and acute seizures developed treatment-resistant postencephalitic epilepsy, with significant predictors including absence of focal slowing on acute EEG, presence of IEDs and PDs on subacute EEG, absence of cell surface antibodies, and absence of early immunotherapy treatment of patients with positive neural antibodies.
#23 Frontiers | Autoimmune Encephalitis in Late-Onset Seizures: When to Suspect and How to Treat
https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2021.633999/full
A follow-up (FU) was carried out in 59% (n = 10/17) of patients with dAE or sAE, with a mean FU time of 40 months (range: 6â102) after the first seizure disorder. Of the remaining seven patients, five (29%) were lost to follow-up (three patients with dAE, two patients with sAE), and two had a follow-up of <6 months. Among those with FU, all were seizure-free at last FU, three of them with the first used ASD. [...] At hospital admission mRS was low (â¤2) in the majority of dAE/sAE patients (n = 12/17, 71%), decreasing to a proportion of 60% (n = 6/10) at last FU. Outcome was favorable for non-paraneoplastic AE (mRS = 0 for all patients with anti-CASPR2 AB and the one patient with anti-LGI1 AB); outcomes in paraneoplastic AE and suspected AE, however, were worse (mRS = 0 in only two patients).
#24 Frontiers | Autoimmune Encephalitis in Late-Onset Seizures: When to Suspect and How to Treat
https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2021.633999/full
A follow-up (FU) was carried out in 59% (n = 10/17) of patients with dAE or sAE, with a mean FU time of 40 months (range: 6â102) after the first seizure disorder. Of the remaining seven patients, five (29%) were lost to follow-up (three patients with dAE, two patients with sAE), and two had a follow-up of <6 months. Among those with FU, all were seizure-free at last FU, three of them with the first used ASD. [...] At hospital admission mRS was low (â¤2) in the majority of dAE/sAE patients (n = 12/17, 71%), decreasing to a proportion of 60% (n = 6/10) at last FU. Outcome was favorable for non-paraneoplastic AE (mRS = 0 for all patients with anti-CASPR2 AB and the one patient with anti-LGI1 AB); outcomes in paraneoplastic AE and suspected AE, however, were worse (mRS = 0 in only two patients).
#25 :: JCN :: Journal of Clinical Neurology
https://thejcn.com/DOIx.php?id=10.3988/jcn.2023.0242
Autoimmune etiologies are a common cause for encephalitis. […] We found that lasting impairments were common among survivors of autoimmune encephalitis, additional research is needed to better understand the nature and impact of these sequelae. […] The mortality rate ranged from 6% to 19%, while the reported relapse risk was 10%38% with the exception of two series, one on LGI-1 encephalitis that reported a relapse rate of 52% and one of MOG encephalitis patients in which it was 62%. […] Based on mRS, most autoimmune encephalitis patients had good outcomes. However, studies measuring in-depth cognitive, psychiatric, or patient-reported outcomes found that ongoing impairments were common, particularly in memory, attention, executive function, and processing speed. […] A comprehensive and more-uniform approach to assessing patients recovering from encephalitis using validated instruments at routine intervals to capture the dimensions of potential ongoing symptoms and sequelae is critical to understanding postencephalitis outcomes.
#26 Seizures and Antibodies Against Surface Antigens (Chapter 9) – Autoimmune Encephalitis and Related Disorders of the Nervous System
https://www.cambridge.org/core/books/autoimmune-encephalitis-and-related-disorders-of-the-nervous-system/seizures-and-antibodies-against-surface-antigens/C222C40DC35C8999D489F33F74A187C3
Seizures are common in all types of autoimmune encephalitis, but their frequency and severity are particularly relevant in anti-NMDAR, anti-GABAbR, anti-GABAaR, and anti-LGI encephalitis. […] Only a small number of patients with anti-NMDAR or anti-GABAbR encephalitis presents as NORSE. […] The term FLAMES (FLAIR-hyperintense Lesions in anti-MOG associated encephalitis with seizures) has been used to describe the encephalitis of some patients with MOG antibodies. […] The clinical presentation includes seizures associated with isolated or predominantly unilateral cortical hyperintense lesions in FLAIR MRI images. […] Seizures and risk of epilepsy in anti-NMDAR, anti-LGI1, and anti-GABAB R encephalitis. […] Seizure outcomes in patients with anti-NMDAR encephalitis: a follow-up study.
#27 :: JCN :: Journal of Clinical Neurology
https://thejcn.com/DOIx.php?id=10.3988/jcn.2023.0242
Autoimmune etiologies are a common cause for encephalitis. […] We found that lasting impairments were common among survivors of autoimmune encephalitis, additional research is needed to better understand the nature and impact of these sequelae. […] The mortality rate ranged from 6% to 19%, while the reported relapse risk was 10%38% with the exception of two series, one on LGI-1 encephalitis that reported a relapse rate of 52% and one of MOG encephalitis patients in which it was 62%. […] Based on mRS, most autoimmune encephalitis patients had good outcomes. However, studies measuring in-depth cognitive, psychiatric, or patient-reported outcomes found that ongoing impairments were common, particularly in memory, attention, executive function, and processing speed. […] A comprehensive and more-uniform approach to assessing patients recovering from encephalitis using validated instruments at routine intervals to capture the dimensions of potential ongoing symptoms and sequelae is critical to understanding postencephalitis outcomes.
#28 :: JCN :: Journal of Clinical Neurology
https://thejcn.com/DOIx.php?id=10.3988/jcn.2023.0242
Autoimmune etiologies are a common cause for encephalitis. […] We found that lasting impairments were common among survivors of autoimmune encephalitis, additional research is needed to better understand the nature and impact of these sequelae. […] The mortality rate ranged from 6% to 19%, while the reported relapse risk was 10%38% with the exception of two series, one on LGI-1 encephalitis that reported a relapse rate of 52% and one of MOG encephalitis patients in which it was 62%. […] Based on mRS, most autoimmune encephalitis patients had good outcomes. However, studies measuring in-depth cognitive, psychiatric, or patient-reported outcomes found that ongoing impairments were common, particularly in memory, attention, executive function, and processing speed. […] A comprehensive and more-uniform approach to assessing patients recovering from encephalitis using validated instruments at routine intervals to capture the dimensions of potential ongoing symptoms and sequelae is critical to understanding postencephalitis outcomes.
#29 :: JCN :: Journal of Clinical Neurology
https://thejcn.com/DOIx.php?id=10.3988/jcn.2023.0242
Autoimmune etiologies are a common cause for encephalitis. […] We found that lasting impairments were common among survivors of autoimmune encephalitis, additional research is needed to better understand the nature and impact of these sequelae. […] The mortality rate ranged from 6% to 19%, while the reported relapse risk was 10%38% with the exception of two series, one on LGI-1 encephalitis that reported a relapse rate of 52% and one of MOG encephalitis patients in which it was 62%. […] Based on mRS, most autoimmune encephalitis patients had good outcomes. However, studies measuring in-depth cognitive, psychiatric, or patient-reported outcomes found that ongoing impairments were common, particularly in memory, attention, executive function, and processing speed. […] A comprehensive and more-uniform approach to assessing patients recovering from encephalitis using validated instruments at routine intervals to capture the dimensions of potential ongoing symptoms and sequelae is critical to understanding postencephalitis outcomes.
#30 Seizures and Antibodies Against Surface Antigens (Chapter 9) – Autoimmune Encephalitis and Related Disorders of the Nervous System
https://www.cambridge.org/core/books/autoimmune-encephalitis-and-related-disorders-of-the-nervous-system/seizures-and-antibodies-against-surface-antigens/C222C40DC35C8999D489F33F74A187C3
Clinical course and features of seizures associated with LGI1-antibody encephalitis. […] The importance of early immunotherapy in patients with faciobrachial dystonic seizures. […] Evaluation of cognitive deficits and structural hippocampal damage in encephalitis with leucine-rich, glioma-inactivated 1 antibodies. […] Seizure semiology in leucine-rich glioma-inactivated protein 1 antibody-associated limbic encephalitis.
#31 Seizures and Antibodies Against Surface Antigens (Chapter 9) – Autoimmune Encephalitis and Related Disorders of the Nervous System
https://www.cambridge.org/core/books/autoimmune-encephalitis-and-related-disorders-of-the-nervous-system/seizures-and-antibodies-against-surface-antigens/C222C40DC35C8999D489F33F74A187C3
Clinical course and features of seizures associated with LGI1-antibody encephalitis. […] The importance of early immunotherapy in patients with faciobrachial dystonic seizures. […] Evaluation of cognitive deficits and structural hippocampal damage in encephalitis with leucine-rich, glioma-inactivated 1 antibodies. […] Seizure semiology in leucine-rich glioma-inactivated protein 1 antibody-associated limbic encephalitis.
#32 Seizures and Antibodies Against Surface Antigens (Chapter 9) – Autoimmune Encephalitis and Related Disorders of the Nervous System
https://www.cambridge.org/core/books/autoimmune-encephalitis-and-related-disorders-of-the-nervous-system/seizures-and-antibodies-against-surface-antigens/C222C40DC35C8999D489F33F74A187C3
Seizures are common in all types of autoimmune encephalitis, but their frequency and severity are particularly relevant in anti-NMDAR, anti-GABAbR, anti-GABAaR, and anti-LGI encephalitis. […] Only a small number of patients with anti-NMDAR or anti-GABAbR encephalitis presents as NORSE. […] The term FLAMES (FLAIR-hyperintense Lesions in anti-MOG associated encephalitis with seizures) has been used to describe the encephalitis of some patients with MOG antibodies. […] The clinical presentation includes seizures associated with isolated or predominantly unilateral cortical hyperintense lesions in FLAIR MRI images. […] Seizures and risk of epilepsy in anti-NMDAR, anti-LGI1, and anti-GABAB R encephalitis. […] Seizure outcomes in patients with anti-NMDAR encephalitis: a follow-up study.
#33 Seizures and Antibodies Against Surface Antigens (Chapter 9) – Autoimmune Encephalitis and Related Disorders of the Nervous System
https://www.cambridge.org/core/books/autoimmune-encephalitis-and-related-disorders-of-the-nervous-system/seizures-and-antibodies-against-surface-antigens/C222C40DC35C8999D489F33F74A187C3
Seizures are common in all types of autoimmune encephalitis, but their frequency and severity are particularly relevant in anti-NMDAR, anti-GABAbR, anti-GABAaR, and anti-LGI encephalitis. […] Only a small number of patients with anti-NMDAR or anti-GABAbR encephalitis presents as NORSE. […] The term FLAMES (FLAIR-hyperintense Lesions in anti-MOG associated encephalitis with seizures) has been used to describe the encephalitis of some patients with MOG antibodies. […] The clinical presentation includes seizures associated with isolated or predominantly unilateral cortical hyperintense lesions in FLAIR MRI images. […] Seizures and risk of epilepsy in anti-NMDAR, anti-LGI1, and anti-GABAB R encephalitis. […] Seizure outcomes in patients with anti-NMDAR encephalitis: a follow-up study.
#34 Seizures, Epilepsy, and NORSE Secondary to Autoimmune Encephalitis: A Practical Guide for Clinicians
https://www.mdpi.com/2227-9059/11/1/44
The most recent International League Against Epilepsy (ILAE) classification has included âimmune etiologyâ along with other well-known causes of epilepsy. […] Most autoimmune encephalitides (AE) present with seizures, but only a minority of cases evolve to long-term epilepsy. […] The risk of epilepsy is higher for patients harboring Abs targeting intracellular antigens (T cell-mediated and mostly paraneoplastic, such as Hu, CV2/CRMP5, Ma2, GAD65 Abs), compared with patients with neuronal surface Abs (antibody-mediated and less frequently paraneoplastic, such as NMDAR, GABAbR, LGI1, CASPR2 Abs). […] Despite the high frequency of seizures and propensity to develop status epilepticus (SE) in the acute stage of autoimmune encephalitis (AE), most patients with AE do not develop an enduring predisposition to seizures over the long-term.
#35 Frontiers | Autoimmune Encephalitis in Late-Onset Seizures: When to Suspect and How to Treat
https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2021.633999/full
Late-onset seizures in non-paraneoplastic AE are known to have a favorable prognosis, corresponding to our findings with a high seizure-free rate with at least one ASD and/or IT. Overall impairment at hospital admission was low (47% mRS 0, 71% mRS â¤2), probably due to the high rate of anti-CASPR2 AB AE (24%) in our patient cohort.
#36 Long-Term Seizure Outcomes in Autoimmune Encephalitis
https://pmc.ncbi.nlm.nih.gov/articles/PMC11962926/
Seizures are common in autoimmune encephalitis (AE), but identifying patients at risk of chronic epilepsy in the post-acute phase remains challenging. This study aims to identify risk factors of treatment-resistant postencephalitic epilepsy. […] Over a median follow-up of 4.9 years, 29.2% developed treatment-resistant postencephalitic epilepsy. Independent predictors of postencephalitic epilepsy included focal slowing on acute EEG (OR 0.15, CI 0.02-0.90), interictal epileptiform discharges (IEDs) or periodic discharges (PDs) on subacute EEG (OR 20.01, CI 1.94-206.44), and cell surface antibodies (OR 0.21, CI 0.05-0.89). Immunotherapy within three months of onset was associated with decreased epilepsy development in patients with neural antibodies (OR 4.16, CI 1.11-16.30). […] Nearly one-third of patients with AE and acute seizures developed treatment-resistant postencephalitic epilepsy, with significant predictors including absence of focal slowing on acute EEG, presence of IEDs and PDs on subacute EEG, absence of cell surface antibodies, and absence of early immunotherapy treatment of patients with positive neural antibodies.
#37 Predictive models in the diagnosis and treatment of autoimmune epilepsy – PubMed
https://pubmed.ncbi.nlm.nih.gov/28555833/
Objective: To validate predictive models for neural antibody positivity and immunotherapy response in epilepsy. […] APE and RITE scores can aid diagnosis, treatment, and prognostication of autoimmune epilepsy.