Clinical trial NCT06515106: Antibody-mediated LGI1 Encephalitis: Symptoms, Biomarkers, and Mechanisms of the Chronic Phase of the Disease
Official title: Antibody-mediated LGI1 Encephalitis: Symptoms, Biomarkers, and Mechanisms of the Chronic Phase of the Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Limbic Encephalitis With LGI1 Antibodies
Keywords: Cognitive Impairment
Encephalitis
Autoimmune
Cognitive rehabilitation
Lead sponsor: Fundacion Clinic per a la Recerca Biomédica
Sponsor class: OTHER
First posted: 2024-07-23
Enrollment: 20
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

Brief summary: The encephalitis mediated by antibodies against Leucine-rich, glioma inactivated 1 protein (anti-LGI1 encephalitis) predominantly affects men (M:F, 6:4) and mostly older than 60 years. The disease has two distinct clinical phases: The acute phase in which the majority of patients develop severe short-term memory deficits (unable to remember events or experiences that occurred a few minutes earlier). This memory impairment can be preceded or accompanied by one or more of the following: hyponatremia (60% of patients), a highly distinctive type of seizures called facio-brachial dystonic seizures (\~40% of patients), along with confusion, irritability and other types of focal seizures or less frequently, generalized seizures. In addition, many patients at this stage have symptoms of REM sleep behavior disorder. In this stage, the CSF may show pleocytosis or mild increase of proteins, the EEG is usually abnormal, and in \~60% of the patients the MRI shows typical increased FLAIR signal in medial temporal lobes (11). There is a clinical sub-phenotype (\~13% of patients) in which the disease presents as a rapidly progressive cognitive decline without the indicated FLAIR MRI changes. About 70% of patients improve rapidly with corticosteroids and immunotherapy (eg, intravenous immunoglobulins and/or plasma exchange), but the improvement is often partial. After the acute phase, there is a chronic or residual phase which represents the interval from improvement of initial symptoms until the disease is considered no longer active and the remaining symptoms are thought to be irreversible. This chronic phase may take several months (it has been less well studied), and is characterized by the absence of CSF pleocytosis and inflammatory MRI changes (albeit this may show residual hippocampal atrophy), and very low or undetectable titers of serum antibodies. Most patients are unable to return to their job or previous activities due to residual (irreversible) memory or cognitive deficits accompanied by signs of moderate brain atrophy. In addition, we and others have shown that about 27-35% of patients have relapsing symptoms after improving from the acute phase (. Although acute symptomatic seizures (facio-brachial dystonic and others) occur in \~90% of patients during the acute phase of the disease, less than 10% of patients develop chronic epilepsy often associated with hippocampal sclerosis. Therefore, the prevailing concept on this disease suggests a syndrome and clinical course in which the acute phase shows rapid, albeit partial, response to immunotherapy, and the symptoms of the chronic phase represent a burnout or irreversible process, in which the disease is no longer active, and the potential improvement of remaining symptoms is uncertain.

Here investigators postulate that a better knowledge of this stage will improve treatment decisions and outcome.

In Aim 1, the post-acute stage will be clinically characterized.

In Aim 2, the impact of cognitive rehabilitation will be assessed.

In Aim 3, a mouse model of anti-LGI1 encephalitis will be used to determine the underlying mechanisms and treatment of the postacute stage.


Eligibility criteria: Inclusion Criteria:

* Patients with Antibody-mediated LGI-1 encephalitis in the post-acute stage of the disease;
* Patients has been discharged from hospital (acute phase).

Exclusion Criteria:

* Inability to obtain informed consent;
* Inability to travel to the center.

Primary outcomes:
measure: Age
timeFrame: 12 months
measure: Gender
timeFrame: 12 months
measure: Handedness
timeFrame: 12 months
measure: General medical history
timeFrame: 12 months
measure: Allergies
timeFrame: 12 months
measure: Symptoms related to anti-LGI1 encephalitis
timeFrame: 12 months
measure: Treatments
timeFrame: 12 months
measure: Functional status
timeFrame: 12 months
measure: Intelligence Quotient
timeFrame: 12 months
measure: Verbal working memory
timeFrame: 12 months
measure: Phonological loop
timeFrame: 12 months
measure: Visual working memory
timeFrame: 12 months
measure: Verbal learning
timeFrame: 12 months
measure: Proactive interference verbal memory
timeFrame: 12 months
measure: Short-term verbal memory
timeFrame: 12 months
measure: Long-term verbal memory
timeFrame: 12 months
measure: Verbal recognition memory
timeFrame: 12 months
measure: Verbal discrimination memory
timeFrame: 12 months
measure: Verbal retention memory
timeFrame: 12 months
measure: Immediate visual memory
timeFrame: 12 months
measure: Delayed visual memory
timeFrame: 12 months
measure: Visual retention memory
timeFrame: 12 months
measure: Visual recognition memory
timeFrame: 12 months
measure: Visual discrimination memory
timeFrame: 12 months
measure: Processing speed
timeFrame: 12 months
measure: TMT-A
timeFrame: 12 months
measure: Naming
timeFrame: 12 months
measure: Naming with cues
timeFrame: 12 months
measure: Latency in naming
timeFrame: 12 months
measure: Semantic fluency
timeFrame: 12 months
measure: Phonemic fluency
timeFrame: 12 months
measure: Visuospatial skills
timeFrame: 12 months
measure: Symbolic gesture right hand - order
timeFrame: 12 months
measure: Symbolic gesture left hand - order
timeFrame: 12 months
measure: Symbolic gesture right hand - imitation
timeFrame: 12 months
measure: Symbolic gesture left hand - imitation
timeFrame: 12 months
measure: Bilateral ideomotor praxis - imitation
timeFrame: 12 months
measure: Stroop test - word subtest
timeFrame: 12 months
measure: Stroop test - color subtest
timeFrame: 12 months
measure: Stroop test - word-color subtest
timeFrame: 12 months
measure: Prensence of psychiatric symptoms or disorders
timeFrame: 12 months
measure: Sleep microstructure - Total study time
timeFrame: 12 months
measure: Sleep microstructure - Total sleep time
timeFrame: 12 months
measure: Sleep microstructure - Sleep efficiency
timeFrame: 12 months
measure: Sleep microstructure - Time to sleep onset
timeFrame: 12 months
measure: Sleep microstructure - Time in stage N1
timeFrame: 12 months
measure: Sleep microstructure - Time in stage N2
timeFrame: 12 months
measure: Sleep microstructure - Time in stage N3
timeFrame: 12 months
measure: Sleep microstructure - Time in stage R
timeFrame: 12 months
measure: Sleep microstructure - First epoch of N1
timeFrame: 12 months
measure: Sleep microstructure - First epoch of N2
timeFrame: 12 months
measure: Sleep microstructure - First epoch of N3
timeFrame: 12 months
measure: Sleep microstructure - First epoch of REM
timeFrame: 12 months
measure: Sleep microstructure - REM/NREM time ratio
timeFrame: 12 months
measure: Sleep microstructure - Number of arousals
timeFrame: 12 months
measure: Sleep microstructure - Arousal Index
timeFrame: 12 months
measure: Sleep microstructure - Confusional arousals
timeFrame: 12 months
measure: Sleep microstructure - Direct transition from N3 to W
timeFrame: 12 months
measure: Sleep microstructure - Delta arousals
timeFrame: 12 months
measure: Sleep microstructure - Wake after sleep
timeFrame: 12 months
measure: Adherence to cognitive treatment - 6 months
timeFrame: 6 months
measure: Adherence to cognitive treatment - 9 months
timeFrame: 9 months
measure: Adherence to cognitive treatment - 12 months
timeFrame: 12 months
measure: Cardiovagal evaluation. (Composite autonomic scoring scale)
timeFrame: 12 months
measure: Valsava ratio
timeFrame: 12 months
measure: Sympathetic evaluation (Composite autonomic scoring scale)
timeFrame: 12 months
measure: Composite Autonomic Symptom Score (Compass-31)
timeFrame: 12 months
measure: Electromyography (EMG)
timeFrame: 12 months
measure: Brainstem reflex
timeFrame: 12 months
measure: MRI
timeFrame: 12 months
measure: EEG: normalcy
timeFrame: 12 months
measure: EEG: time awake
timeFrame: 12 months
measure: EEG: time in drowsiness
timeFrame: 12 months
measure: EEG: time asleep
timeFrame: 12 months
measure: EEG: epileptiform activity
timeFrame: 12 months
measure: EEG: seizures
timeFrame: 12 months
measure: EEG: slowing
timeFrame: 12 months
measure: EEG: Changes with Intermittent Light Stimulation
timeFrame: 12 months
measure: EEG: Changes with hyperventilation
timeFrame: 12 months
Secondary outcomes:
measure: LGI-1 antibodies
timeFrame: 12 months
measure: HLA genotyping
timeFrame: 12 months
measure: Immune/inflammatory signaling-target gene expression pathways
timeFrame: 12 months
measure: NfL levels
timeFrame: 12 months
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Hospital Clínic de Barcelona
state: Cataluña
Study officials:
affiliation: Hospital Clínic
name: Josep Dalmau, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Fundacion Clinic per a la Recerca Biomédica
name: Lorena Rami, PhD
role: PRINCIPAL_INVESTIGATOR
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