Faciobrachio-crural dystonic seizures in LGI1 limbic encephalitis: A treatable cause of falls.
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ABSTRACT:
SUBMITTER: Ismail FS
PROVIDER: S-EPMC4547877 | biostudies-literature | 2015 Oct
REPOSITORIES: biostudies-literature
Publications
Faciobrachio-crural dystonic seizures in LGI1 limbic encephalitis: A treatable cause of falls.
Ismail Fatme Seval FS Popkirov Stoyan S Wellmer Jörg J Grönheit Wenke W
Neurology(R) neuroimmunology & neuroinflammation 20150820 5
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| S-EPMC5802484 | biostudies-literature
Project description:ObjectiveTo characterize the clinical features and MRI abnormalities of leucine-rich glioma-inactivated 1 (LGI1)-autoantibody (Ab) faciobrachial dystonic seizures (FBDS).MethodsForty-eight patients with LGI1-Ab encephalopathy were retrospectively identified by searching our clinical and serologic database from January 1, 2002, to June 1, 2015. Of these, 26 met inclusion criteria for this case series: LGI1-Ab seropositivity and FBDS. In a separate analysis of all 48 patients initially identified, the MRIs of patients with (n = 26) and without (n = 22) FBDS were compared by 2 neuroradiologists blinded to the clinical details.ResultsThe median age of the 26 included patients was 62.5 years (range 37-78); 65% were men. FBDS involved arm (26), face (22), and leg (12). Ten were previously diagnosed as psychogenic. Ictal EEGs were normal in 20 of 23 assessed. Basal ganglia T1 and T2 signal abnormalities were detected in 11 patients (42%), with excellent agreement between neuroradiologists (κ scores of 0.86 and 0.93, respectively), and included T1 hyperintensity alone (2), T2 hyperintensity alone (1), or both (8). The T1 hyperintensities persisted longer than the T2 hyperintensities (median 11 weeks vs 1 week, p = 0.02). Improvement with immunotherapy (18/18) was more frequent than with antiepileptic medications (10/24). A separate analysis of all 48 patients initially identified with LGI1-Ab encephalopathy showed that basal ganglia MRI abnormalities were present in 11 of 26 with FBDS but not present in those without FBDS (0/22) (p < 0.001). In contrast, mesial temporal MRI abnormalities were less common among those with FBDS (42%) than those without (91%) (p < 0.001).ConclusionsBasal ganglia T1 hyperintensity is a clinically useful MRI biomarker of LGI1-Ab FBDS and suggests a basal ganglia localization.
| S-EPMC4592539 | biostudies-literature
Project description:This case report describes a rare but classic presentation of a non-paraneoplastic, antibody-mediated limbic encephalitis. The clinical course did put us in a limbo as it evolved from seizure to Parkinsonism and then from metastasis to stroke, before it finally announced itself by its pathognomonic finding. Knowledge of this rare condition is important as early identification and treatment can change the course.
| S-EPMC7099203 | biostudies-literature
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| S-EPMC3090064 | biostudies-literature
Project description:Human leucine-rich glioma-inactivated protein 1 encephalitis (LGI1) is an autoimmune limbic encephalitis in which serum and cerebrospinal fluid contain antibodies targeting LGI1, a protein of the voltage gated potassium channel (VGKC) complex. Recently, we showed that a feline model of limbic encephalitis with LGI1 antibodies, called feline complex partial seizures with orofacial involvement (FEPSO), is highly comparable to human LGI1 encephalitis. In human LGI1 encephalitis, neuropathological investigations are difficult because very little material is available. Taking advantage of this natural animal model to study pathological mechanisms will, therefore, contribute to a better understanding of its human counterpart. Here, we present a brain-wide histopathological analysis of FEPSO. We discovered that blood-brain barrier (BBB) leakage was present not only in all regions of the hippocampus but also in other limbic structures such as the subiculum, amygdale, and piriform lobe. However, in other regions, such as the cerebellum, no leakage was observed. In addition, this brain-region-specific immunoglobulin leakage was associated with the breakdown of endothelial tight junctions. Brain areas affected by BBB dysfunction also revealed immunoglobulin and complement deposition as well as neuronal cell death. These neuropathological findings were supported by magnetic resonance imaging showing signal and volume increase in the amygdala and the piriform lobe. Importantly, we could show that BBB disturbance in LGI1 encephalitis does not depend on T cell infiltrates, which were present brain-wide. This finding points toward another, so far unknown, mechanism of opening the BBB. The limbic predilection sites of immunoglobulin antibody leakage into the brain may explain why most patients with LGI1 antibodies have a limbic phenotype even though LGI1, the target protein, is ubiquitously distributed across the central nervous system.
| S-EPMC5651237 | biostudies-literature
Project description:More than 30 mutations in LGI1, a secreted neuronal protein, have been reported with autosomal dominant lateral temporal lobe epilepsy (ADLTE). Although LGI1 haploinsufficiency is thought to cause ADLTE, the underlying molecular mechanism that results in abnormal brain excitability remains mysterious. Here, we focused on a mode of action of LGI1 autoantibodies associated with limbic encephalitis (LE), which is one of acquired epileptic disorders characterized by subacute onset of amnesia and seizures. We comprehensively screened human sera from patients with immune-mediated neurological disorders for LGI1 autoantibodies, which also uncovered novel autoantibodies against six cell surface antigens including DCC, DPP10, and ADAM23. Our developed ELISA arrays revealed a specific role for LGI1 antibodies in LE and concomitant involvement of multiple antibodies, including LGI1 antibodies in neuromyotonia, a peripheral nerve disorder. LGI1 antibodies associated with LE specifically inhibited the ligand-receptor interaction between LGI1 and ADAM22/23 by targeting the EPTP repeat domain of LGI1 and reversibly reduced synaptic AMPA receptor clusters in rat hippocampal neurons. Furthermore, we found that disruption of LGI1-ADAM22 interaction by soluble extracellular domain of ADAM22 was sufficient to reduce synaptic AMPA receptors in rat hippocampal neurons and that levels of AMPA receptor were greatly reduced in the hippocampal dentate gyrus in the epileptic LGI1 knock-out mouse. Therefore, either genetic or acquired loss of the LGI1-ADAM22 interaction reduces the AMPA receptor function, causing epileptic disorders. These results suggest that by finely regulating the synaptic AMPA receptors, the LGI1-ADAM22 interaction maintains physiological brain excitability throughout life.
| S-EPMC3828467 | biostudies-literature
Project description:Magnetic resonance imaging has linked chronic voltage-gated potassium channel (VGKC) complex antibody-mediated limbic encephalitis with generalized hippocampal atrophy. However, autoantibodies bind to specific rodent hippocampal subfields. Here, human hippocampal subfield (subiculum, cornu ammonis 1-3, and dentate gyrus) targets of immunomodulation-treated LGI1 VGKC-complex antibody-mediated limbic encephalitis were investigated using in vivo ultra-high resolution (0.39 × 0.39 × 1.0 mm3) 7.0 T magnetic resonance imaging [n = 18 patients, 17 patients (94%) positive for LGI1 antibody and one patient negative for LGI1/CASPR2 but positive for VGKC-complex antibodies, mean age: 64.0 ± 2.55 years, median 4 years post-limbic encephalitis onset; n = 18 controls]. First, hippocampal subfield quantitative morphometry indicated significant volume loss confined to bilateral CA3 [F(1,34) = 16.87, P < 0.0001], despite hyperintense signal evident in 5 of 18 patients on presentation. Second, early and later intervention (<3 versus >3 months from symptom onset) were associated with CA3 atrophy. Third, whole-brain voxel-by-voxel morphometry revealed no significant grey matter loss. Fourth, CA3 subfield atrophy was associated with severe episodic but not semantic amnesia for postmorbid autobiographical events that was predicted by variability in CA3 volume. The results raise important questions about the links with histopathology, the impact of the observed focal atrophy on other CA3-mediated reconstructive and episodic mechanisms, and the role of potential antibody-mediated pathogenicity as part of the pathophysiology cascade in humans.
| S-EPMC5405234 | biostudies-literature
Project description:We utilise a clinical case to highlight why exclusion of voltage-gated potassium channel (VGKC)-complex autoantibody testing in serological evaluation of patients may delay or miss the diagnosis. A 68-year-old man presented with increasing involuntary movements consistent with faciobrachial dystonic seizures (FBDS). Initial evaluation demonstrated VGKC antibody seropositivity with leucine-rich glioma-inactivated 1 (LGI1) and contactin-associated protein-like 2 (CASPR2) seronegativity. Aggressive immunotherapy with methylprednisolone and plasmapheresis was started early in the course of his presentation. Following treatment with immunotherapy, the patient demonstrated clinical improvement. Repeat serum evaluation 4 months posthospitalisation remained seropositive for VGKC-complex antibodies, with development of LGI1 autoantibody seropositivity. VGKC-complex and LGI1 antibodies remained positive 12 months posthospitalisation. Our findings suggest that clinical symptoms can predate the detection of the antibody. We conclude that when suspicion for autoimmune encephalitis is high in the setting of VGKC autoantibody positivity, regardless of LGI1 or CASPR2 seropositivity, early immunotherapy and repeat testing should be considered.
| S-EPMC5534759 | biostudies-other
Project description:PurposeTo describe clinical and electrographic characteristics of seizures LGI1-antibody encephalitis, and their correlations with two-year outcomes.MethodsVideo-electroencephalography recordings were performed on a cohort of 16 consecutive patients with LGI1-antibodies from two UK neuroscience-centers over five-years.ResultsFrom 14 of 16 patients (13 males; age-range 53-92years), 86 faciobrachial dystonic seizures were recorded at a median frequency of 0.4 per hour (range 0.1-9.8), and ictal EEG changes accompanied 5/86 events. In addition, 11/16 patients showed 53 other seizures - subclinical (n=18), motor (n=16), or sensory (n=19) - at a median of 0.1 per hour (range 0.1-2) associated with temporal and frontal discharges. The sensory events were most commonly thermal sensations or body-shuddering, and the motor events were frequently automatisms or vocalisations. Furthermore, multifocal interictal epileptiform discharges, from temporal, frontal and parietal regions, and interictal slow-wave activity were observed in 25% and 69% of patients, respectively. Higher observed seizure frequency correlated with poorer functional recovery at two-years (p=0.001).ConclusionsMultiple frequent seizure semiologies, in addition to numerous subclinical seizures and interictal epileptiform discharges, are hallmarks of LGI1-antibody encephalitis. High overall seizure frequency may predict more limited long-term recovery. These observations should encourage closer monitoring and proactive treatment of seizure activity in these patients.
| S-EPMC5558811 | biostudies-literature