Motor cortex and hippocampus are the two main cortical targets in LGI1-antibody encephalitis

Abstract

à These authors contributed equally to this work. Encephalitis associated with antibodies against leucine-rich glioma-inactivated 1 (LGI1) protein is increasingly recognized as an auto-immune disorder associated with characteristic tonic-dystonic seizures. The cortical or subcortical origin of these motor events is not clear. Some patients also present with different epileptic seizures and with cognitive impairment. The frequency of these features and their timing during the natural history of this encephalitis have not been fully described. We therefore reviewed data from 34 patients harbouring antibodies against LGI1 protein (21-81 years, median age 64) referred to the French Reference Centre for Neurological Paraneoplastic Syndrome. Three types of evidence suggested tonic-dystonic seizures were of cortical origin: (i) a slow, unilateral, frontal electroencephalographic wave, of duration $580 ms and amplitude $71 mV, preceded the contralateral tonic-dystonic seizures in simultaneous electroencephalographic and myographic records from seven of seven patients tested; (ii) 18-Fluorodeoxyglucose imaging revealed a strong hypermetabolism in primary motor cortex, controlateral to the affected limb, during encephalitis for five patients tested, as compared with data from the same patients after remission or from 16 control subjects; and (iii) features of polymyographic records of tonic-dystonic seizure events pointed to a cortical origin. Myoclonic patterns with brief, rhythmic bursts were present in three of five patients tested and a premyoclonic potential was identified in the cortex of one patient. Initially during encephalitis, 11 of 34 patients exhibited tonic-dystonic seizures (32%). Distinct epileptic syndromes were evident in 13 patients (38%). They were typically simple, focal seizures from the temporal lobe, consisting of vegetative symptoms or fear. At later stages, 22 of 32 patients displayed tonic-dystonic seizures (68%) and 29 patients presented frequent seizures (91%) including status epilepticus. Cognitive impairment, either anterograde amnesia or confusion was evident in 30 of 34 patients (88%). Brain imaging was normal in patients with isolated tonic-dystonic seizures; in patients with limbic symptoms it revealed initially a hippocampal hyperintensity in 8 of 19 patients (42%) and 17 of 24 patients (70%) at later stages. Our data suggest that the major signs of LGI1-antibody encephalitis can be linked to involvement of motor cortex and hippocampus. They occur in parallel with striatum involvement. One of these cortical targets is involved, often unilaterally at disease onset. As the encephalitis progresses, in the absence of immunomodulatory treatment, the second cortical target is affected and effects become bilateral. Progression to the second cortical target occurs with a variable delay of days to several months.

Paraneoplastic epilepsy

“…Characteristic unilateral frontal slow EEG potentials, which preceded the contralateral tonic-dystonic seizures, were recorded in all seven tested patients. The FDG-PET confirmed hypermetabolism in primary motor cortex contralateral to the affected limb [71]. The LGI1 antibodies seem to have two main cortical targets: the motor cortex and the hippocampus.…”

Beyond the limbic system: disruption and functional compensation of large-scale brain networks in patients with anti-LGI1 encephalitis

“…A recent FDG-PET analysis reported hypermetabolism of the sensorimotor cortex in patients with anti-LGI1 encephalitis that, together with contralateral frontal EEG changes and results from polymyographic recordings, are suggestive of a motor cortex origin of FBDS 5. Another FDG-PET study observed hypermetabolism in the precentral gyrus, basal ganglia and cerebellum in patients with LGI1 encephalitis with FBDS 16.…”

Diagnostic Value of18F-FDG PET/CT Versus MRI in the Setting of Antibody-Specific Autoimmune Encephalitis

“…They have shown that most patients with diffuse cerebral hypometabolism had clinical syndromes consistent with encephalitis (72.2% patients) (34). However, a heterogeneous pattern of brain metabolism has been reported on the brain 18 F-FDG PET/CT of patients with AE so far (34)(35)(36)(37)(38). Some previous case reports described hypermetabolism of cerebral cortices or striatum as a predominant feature of autoimmune encephalitides (35,(37)(38)(39).…”