Antiepileptic drug therapy in patients with autoimmune epilepsy anoxia adalah

Results:

The medical records of 252 adult patients diagnosed with autoimmune encephalitis and paraneoplastic disorders were reviewed. Seizure was the initial presentation in 50 patients (20%). Serum and/or CSF autoantibodies were detected in 41 (82%) patients, and 38 (76%) patients had neural autoantibodies. The majority (n = 43, 86%) received at least 1 form of immunotherapy in combination with aeds, while the remainder received aeds alone. Twenty-seven patients (54%) became seizure free: 18 (36%) with immunotherapy, 5 (10%) with aeds alone, and 4 (8%) with aeds after immunotherapy failure. Levetiracetam was the most commonly used (42/50); however, it was associated with 0% seizure-free response.Anoxia adalah


AED seizure-free responses occurred with carbamazepine (n = 3) [3/16, 18.8%], lacosamide (n = 3) [3/18, 16.6%] with phenytoin (n = 1) [1/8, 12.5%], or oxcarbazepine (n = 2) [2/11, 18.1%]. Regardless of the type of therapy, voltage-gated potassium channel-complex antibody–positive patients were more likely to become seizure free compared with glutamic acid decarboxylase 65 antibody–positive cases (12/17 vs 2/10, p = 0.0183).

Autoimmune epilepsy (AE) has been linked to both antineural antibodies targeting neural intracellular proteins (GAD65, ANNA-1, ma, etc) and cell surface antigens (voltage-gated potassium channel–complex [VGKC-complex], NMDA receptor, AMPA, GABA-B, mglur5, etc). AE can occasionally occur in the absence of detected neural antibodies as well. 1 valuable clinical clues for AE are subacute onset, an unusually high seizure frequency, intraindividual seizure variability or multifocality, antiepileptic drug (aeds) resistance, personal or family history of autoimmunity, or history of recent or past neoplasia. 2 seizures occur as an early and prominent feature in AE, and these are characteristically refractory to conventional AED therapy. 1

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Although intractability is a common feature in AE, some respond to aeds, and they remain an important aspect of therapy. The role of aeds in these patients is also relevant as even after controlling the inflammatory response, some patients remain at risk of recurrent seizures, particularly if cerebral damage occurred during the acute encephalitic phase of the illness. Some aeds affect cellular and humoral immune responses. 3, – 6 for example, carbamazepine and valproate have been shown to increase the serum levels of IL-1β, IL-2, IL-4, IL-6, IL-17, and tumor necrosis factor–alpha (tnfα) production. 4, 5 at this time, no single AED stands out as superior to others in AE, and the medically refractory nature of seizures in these patients is typically emphasized.Anoxia adalah however, occasional patients do respond to AED treatment, and it is not currently known if this occurs with medications featuring particular mechanisms of action. In this study, we aimed to explore the pattern of usage and relative efficacy of aeds in patients with AE.

Treatments and response.

The majority (n = 43, 86%) received at least 1 form of immunotherapy in combination with aeds, while the reminder received aeds alone. The median number of aeds used was 2 (range 1–6). Levetiracetam was the most common medication used (n = 42), followed by lacosamide (n = 18), carbamazepine (n = 16), oxcarbazepine (n = 11), lamotrigine (n = 11), and phenytoin (n = 8). Summary of AED use for the cohort is provided in figure 2.Anoxia adalah in addition, 4 patients received vagus nerve stimulation therapy, and 3 patients had unsuccessful epilepsy surgeries. The rationale for selecting one AED over the other was not clarified in the electronic medical record (EMR). Twenty-seven patients (54%) became seizure free: 18 (36%) with immunotherapy, 5 (10%) with aeds alone, and 4 (8%) with aeds after failing immunotherapy. Initiation of carbamazepine (n = 3) (3/16, 18.8%), lacosamide (n = 3) (3/18, 16.6%), phenytoin (n = 1) (1/8, 12.5%), or oxcarbazepine (n = 2) (2/11, 18.1%) resulted in seizure-free outcomes, while none of the patients became seizure free with levetiracetam (n = 0) (0/42, 0%). The timing of therapeutic response to aeds (i.E., cessation of clinical seizures) was immediate: within 24 hours in 1 patient, within 1 week in 2, within 2 weeks in 3, and within 4 weeks in the remainder.Anoxia adalah

Pattern of AED use in 50 patients with suspected AE

Among those who responded to AED therapy, 4 were VGKC-complex antibody positive (1 LGI1, 1 CASPR2, and 2 double negative), 1 was GAD65 antibody positive, 1 was achr antibody positive, 1 was TPO antibody positive, and 2 were autoantibody negative. Regardless of the type of therapy, VGKC-complex antibody–positive patients were more likely to become seizure free compared with GAD65-positive and autoimmune antibody–negative cases (12/17 vs 2/10 vs 2/9 respectively, p 0.05). Specifically, of the VGKC-complex antibody patients who became seizure free, 4 responded to aeds (25%), while the remainder became seizure free with immunotherapy (75%). One patient with GAD65 ab-associated AE responded to carbamazepine, while the other became seizure free with immunotherapy.Anoxia adalah two of the autoantibody-negative cases responded to aeds (carbamazepine), and 2 became seizure free with immunotherapy. Details of patients who responded to aeds alone or after failure of immunotherapy are summarized in table 2 and figure 3.

DISCUSSION

Although the seizures in AE are often considered to be medication resistant, and immunotherapy is often the focus of management, 7 this study suggests that in select cases aeds alone may confer seizure freedom.

Of interest in our study, 9 patients became seizure free after the initiation of aeds with sodium channel blocking properties 7 (carbamazepine, n = 3; oxcarbazepine, n = 2; lacosamide alone, n = 3, or with phenytoin, n = 1). The response to aeds was seen within 2–4 weeks of the initiation of therapy in all patients.Anoxia adalah in a few patients, aeds alone were effective in controlling seizures. However, improvement of cognitive symptoms and other manifestations of autoimmune encephalitis in most patients requires immunotherapy. 7 it is conceivable that these therapeutic responses could be secondary to immunomodulatory properties of these medications. 4, – 6 for example, carbamazepine has been shown to reduce levels of proinflammatory cytokines IL-1β and tnfα in the hippocampus of rats 4 and inhibits the development of different types of inflammation through dose-dependent reduction of prostaglandin E2 and substance P. 5 carbamazepine and oxcarbazepine have also been shown to decrease serum levels of IL-1 and IL-2 in healthy subjects. 5 although disruption of blood-brain barrier permeability has been suggested as a possible pathway for cytokines influencing seizures and epilepsy, 8 the exact role of cytokines in human epilepsy is complex and not yet completely elucidated.Anoxia adalah moreover, whether there are unique aspects of the pathophysiology of seizure onset in these patients which make them more susceptible to sodium channel blockage is not known. The observed response could also be due to the effectiveness of sodium channel blockers in focal onset epilepsy which is seen in 66% of patients in our cohort. Of note, while AED responders responded to sodium channel blockers, no patient responded to lamotrigine, which also has sodium channel properties. 9 therefore, if there is a unique responsivity of seizures in these patients to this class of medications, the response may not be uniform throughout the entire class. Studies are needed to elucidate whether any differential efficacy is based on their effect on seizure mechanisms or immunomodulatory properties.Anoxia adalah

Regardless of the type of therapy, VGKC-complex antibody–positive patients were more likely to become seizure free compared with GAD65-positive and autoimmune antibody–negative cases ( figure 2). This is consistent with previous observations of superior immunotherapy response in patients with neural surface–related autoantibody-mediated encephalitides as compared to those associated with intracellular antigen autoantibodies. 1, 7, 10 of note, among the patients who responded to aeds in our cohort, the majority were VGKC-complex antibody positive (1 LGI1 positive; 1 CASPR2 positive, and 2 double negative). Two of these responded to oxcarbazepine, one to lacosamide, and the other to carbamazepine ( figure 1).Anoxia adalah indeed, sodium-channel blocking agents such as carbamazepine and phenytoin have been successfully used to treat autoimmune VGK channelopathies such as neuromyotonia 11 and episodic ataxia type 1. 12 these agents act by reducing neuronal repetitive firing through interaction with voltage-gated sodium channels. 11, 12 perhaps, the observed favorable response of these agents in VGKC-complex ab–associated AE is attributable to this mechanism. In our series, one patient with GAD65 ab–associated AE became seizure free with carbamazepine after failing immunotherapy. This is in contrast to a similar report that found lack of AED response in patients with GAD65 antibody–positive AE following which it was postulated that GAD65 ab–associated aes are intractable to aeds. 13 regardless of the type of therapy, 4/9 (44.4%) autoantibody-negative patients become seizure free, 2 with aeds (one with lacosamide and the other with carbamazepine after failing immunotherapy), while the other two responded to immunotherapy.Anoxia adalah others have noted the potential for response in patients with seronegative AE to antiepileptic medication and immunotherapy. 14

The rationale for selecting one AED over the other was not clarified in the EMR of our cohort. Levetiracetam was the most common used drug (42/50, figure 2); however, none of the patients in our series were rendered seizure free by this medication (0%). This finding is in contrast to previous reports suggesting that levetiracetam may have, at least in part, anti-inflammatory properties. 3 the reason for the prevalent use of levetiracetam in our series is likely due to its ease of dosing and lack of drug-drug interactions. 9 certainly, aeds with enzyme induction properties such as carbamazepine and phenytoin could alter the pharmacokinetics of immunosuppressive therapies and other agents used in these patients. 9 perhaps, newer aeds with sodium channel blocking properties and more favorable pharmacokinetic profiles (such as oxcarbazepine and lacosamide) could be considered in this patient population.Anoxia adalah it is also imperative to monitor for hyponatremia (e.G., oxcarbazepine and carbamazepine) and allergic cutaneous reactions (e.G., carbamazepine and phenytoin), as these have been shown to occur at high rate in patients with VGKC-complex antibody. 15 prospective studies are needed to clarify AED selection and to elucidate their immunomodulatory properties in AE.

There are several limitations to our study. First, data collection for this retrospective study was based on the extraction of relevant patient information from emrs. The lack of control group and the possible confounder of concomitant immunotherapy should also be acknowledged. In addition, selection bias could be present due to the tertiary nature of these patients.Anoxia adalah finally, seizure quantification is only based on verbal report, thus recall bias could result in the event of amnestic seizures, and related to concurrent cognitive dysfunction that may have been present in a significant proportion of our cohort. Prospective studies are needed to clarify whether there is an optimal AED selection for AE. As the awareness of AE increases, finding effective strategies for seizure control is crucial.