Winawer, M. R. et al. Autosomal dominant partial epilepsy with auditory features: defining the phenotype. Neurology 54, 2173-2176

G.H. Sergievsky Center and Mailman School of Public Health, Department of Neurology, Columbia University, New York, NY 10032, USA.
Neurology (Impact Factor: 8.29). 07/2000; 54(11):2173-6. DOI: 10.1212/WNL.54.11.2173
Source: PubMed


The authors previously reported linkage to chromosome 10q22-24 for autosomal dominant partial epilepsy with auditory features. This study describes seizure semiology in the original linkage family in further detail. Auditory hallucinations were most common, but other sensory symptoms (visual, olfactory, vertiginous, and cephalic) were also reported. Autonomic, psychic, and motor symptoms were less common. The clinical semiology points to a lateral temporal seizure origin. Auditory hallucinations, the most striking clinical feature, are useful for identifying new families with this synome.

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Available from: Melodie R Winawer, Mar 24, 2014
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    • "In some patients, seizures are induced by acoustic stimuli such as sudden noises or answering the phone (Winawer et al., 2000; Michelucci et al., 2003, 2007), indicating a lateral temporal lobe onset. Some MRI studies have reported developmental abnormalities in the left Abbreviations: ADLTE, autosomal dominant lateral temporal lobe epilepsy; AGS, audiogenic seizures; EEG, electroencephalography; ENU, N-ethyl-N-nitrosourea; GTCS, generalized tonic–clonic seizures; IR, immunoreactivity; Lgi1, leucine-rich, glioma inactivated 1. * Corresponding author at: Institute of Laboratory Animals, Graduate School of Medicine, Kyoto University, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan. "
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    ABSTRACT: Mutations in the leucine-rich, glioma inactivated 1 (LGI1) gene have been identified in patients with autosomal dominant lateral temporal lobe epilepsy (ADLTE). We previously reported that Lgi1 mutant rats, carrying a missense mutation (L385R) generated by gene-driven N-ethyl-N-nitrosourea (ENU) mutagenesis, showed generalized tonic-clonic seizures (GTCS) in response to acoustic stimuli. In the present study, we assessed clinically-relevant features of Lgi1 heterozygous mutant rats (Lgi1(L385R/+)) as an animal model of ADLTE. First, to explore the focus of the audiogenic seizures, we performed electroencephalography (EEG) and brain Fos immunohistochemistry in Lgi1(L385R/+) and wild type rats. EEG showed unique seizure patterns (e.g., bilateral rhythmic spikes) in Lgi1(L385R/+) rats with GTCS. An elevated level of Fos expression indicated greater neural excitability to acoustic stimuli in Lgi1(L385R/+) rats, especially in the temporal lobe, thalamus and subthalamic nucleus. Finally, microarray analysis revealed a number of differentially expressed genes that may be involved in epilepsy. These results suggest that Lgi1(L385R/+) rats are useful as an animal model of human ADLTE.
    Full-text · Article · Jan 2014 · Neuroscience Research
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    • "ADPEAF patients present with complex partial and secondarily generalized seizures that are often associated with auditory auras (Nobile et al., 2009; Michelucci et al., 2013). The average age of seizure onset is in early adulthood (Winawer et al., 2000) and subtle abnormalities have been observed by magnetic resonance imaging from ADPEAF patients (Kobayashi et al., 2003; Tessa et al., 2007). This suggests that ADPEAF results from defects in brain development, which is consistent with the hypothesized functions for LGI1. "
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    ABSTRACT: The development and function of the vertebrate nervous system depends on specific interactions between different cell types. Two examples of such interactions are synaptic transmission and myelination. Leucine-rich Glioma Inactivated proteins (LGI1-4) play important roles in these processes. They are secreted proteins consisting of a Leucine-rich repeat (LRR) domain and a so-called epilepsy associated or epitempin (EPTP) domain. Both domains are thought to function in protein-protein interactions. The first LGI gene to be identified, LGI1, was found at a chromosomal translocation breakpoint in a glioma cell line. It was subsequently found mutated in Autosomal Dominant Lateral Temporal (lobe) Epilepsy (ADLTE) also referred to as Autosomal Dominant Partial Epilepsy with Auditory Features (ADPEAF). LGI1 protein appears to act at synapses and antibodies against LGI1 may cause the autoimmune disorder limbic encephalitis. A similar function in synaptic remodeling has been suggested for LGI2, which is mutated in canine Benign Familial Juvenile Epilepsy. LGI4 is required for proliferation of glia in the peripheral nervous system and binds to a neuronal receptor, ADAM22, to foster ensheathment and myelination of axons by Schwann cells. Thus, LGI proteins play crucial roles in nervous system development and function and their study is highly important, both to understand their biological functions and for their therapeutic potential. Here we review our current knowledge about this important family of proteins, and the progress made toward understanding their functions.
    Full-text · Article · May 2013 · ASN Neuro
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    • "Autosomal dominant lateral temporal lobe epilepsy (ADLTE) is an epilepsy syndrome characterized by focal seizures with auditory auras sometimes triggered by external noises [1] [2] [3]. There are also aphasic seizures, visual hallucinations, and a high propensity to generalized seizures. "
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    ABSTRACT: Autosomal dominant lateral temporal lobe epilepsy (ADLTE) is characterized by focal seizures with auditory features or aphasia. Mutations in the leucine-rich glioma-inactivated 1 (LGI1) gene have been reported in up to 50% of families with ADLTE. Attention-deficit/hyperactivity disorder (ADHD) symptoms have not yet been reported in these families. Clinical data were collected from a family with five affected members. Leucine-rich glioma-inactivated 1 exons and boundaries were sequenced by standard methods. Attention-deficit/hyperactivity disorder symptoms were scored based on the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria. Affected members had seizures with auditory features and psychic auras, and some experienced nightmares. A heterozygous c.431+1G>A substitution in LGI1 was detected in all members. Significantly more hyperactivity symptoms were found in family members carrying the LGI1 mutation. This study expands the phenotypic spectrum associated with ADLTE due to LGI1 mutation and underlines the need for more systematic evaluation of ADHD and related symptoms.
    Full-text · Article · May 2013 · Epilepsy & Behavior
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