[Clinical Characteristics of Autoimmune Disease with Dual Seropositive Antibodies of Leucine-rich Glioma Inactivated 1 and Contactin-associated Protein 2].

Objective To explore the clinical characteristics of autoimmune disease with dual seropositive antibodies of leucine-rich glioma inactivated 1(LGI1)and contactin-associated protein 2(Caspr2).Methods The clinical data of seven patients with dual seropositive LGI1 and Caspr2 antibodies who were admitted to the Neurology Department of Peking Union Medical College Hospital from July 2014 to December 2017 were retrospectively analyzed.Results Central,peripheral and autonomic nervous systems were all involved in the seven cases;100%(7/7)presented with insomnia,myokymia,neuropahic pain and hyperhydrosis;71%(5/7)showed memory decline or psychiatric and behavioral symptoms;57%(4/7)had urinary hesitation or constipation;and 43%(3/7)had seizure.Electromyography showed 100%(6/6) of the patients had prolonged afterdischarges following normal M waves and/or abnormal spontaneous firing.Electroencephalography revealed slow waves or basic rhythm slowing in 71%(5/7)of patients.Electrocardiography showed sinus tachycardia,axis deviation,and prolonged QT intervals in 71%(5/7)of patients.One patient died from arrhythmia before immunotherapy.One died from pulmonary infection after immunotherapy.Improvement with immunotherapy was documented in the other five cases.No relapse was noted during the 1-2-year follow-up.Conclusions Autoimmune disease with dual seropositive antibodies of LGI1 and Caspr2 can diffusely affect the central,peripheral,and autonomic nervous systems.The possibility of this disease should be considered in patients with acute and subacute onset of neuropsychiatric symptoms,especially in patients with accompanying insomnia,myokymia,and hyperhydrosis.

Mutations in PRRT2 result in paroxysmal dyskinesias with marked variability in clinical expression.

BACKGROUND: Paroxysmal dyskinesias (PDs), a clinically and genetically heterogeneous group of episodic movement disorders, include kinesigenic PD (PKD), exercise-induced PD (PED) and non-kinesigenic PD (PNKD). These disorders are all transmitted as autosomal dominant traits with incomplete penetrance. Several PD-related genetic disorders, including PKD and familial infantile convulsions with paroxysmal choreoathetosis (ICCA), mapped to the same region on chromosome 16. Independent genetic studies have recently revealed that PKD can be caused by loss-of-function mutations in the proline-rich transmembrane protein 2 gene (PRRT2). We tested the hypothesis that other forms of PDs are also due to PRRT2 mutations. METHODS/RESULTS: The whole genomic region of PRRT2 was sequenced in six Han Chinese families and 15 sporadic cases of PD-related phenotypes. The previously reported mutation, c.649dupC (p.R217Pfs*7), was found in two families with PKD, one family with ICCA, one family with PNKD-like phenotype, and two sporadic cases with PED. In an additional ICCA family, a novel frameshift mutation, c.904dupG (p.D302Gfs*38), was identified. A missense mutation, c.913G→A (p.G305R), and a synonymous substitution, c.1011C→T (p.G337G), were also detected in two sporadic PKD cases. CONCLUSION: This study shows that PKD, ICCA and some other PD-related phenotypes are part of the same phenotypic spectrum, caused by mutations in PRRT2. This underscores the complexity of the phenotypic consequences of PRRT2 mutations.

New-Onset Geriatric Epilepsy in China: A Single-Center Study.

BACKGROUND: Few studies have been published on new-onset geriatric epilepsy especially in older Chinese people. This study was to have a comprehensive understanding of new-onset geriatric epilepsy and find a more reasonable diagnosis and management of epilepsy in older people. METHODS: One hundred and three patients with onset age 60 years and older were admitted between January 2008 and December 2016. Electronic medical records were reviewed to collect information. RESULTS: There were 103 older patients with new-onset epilepsy. The mean age of the patients was 68.5 ± 6.4 years (range: 60-89 years), and there were 67 (65%) men and 36 (35%) women. The mean onset age was 67.9 ± 6.2 years (range: 60-89 years). The most common identifiable etiology of symptomatic seizures was autoimmune epilepsy in 43 (41.7%) patients. The second most common etiology was stroke in 15 (14.6%) patients. Seven (6.8%) older patients with acute seizures present with status epilepticus and 26 (25.2%) patients experienced clustered seizures (more than three events in 24 h) at seizure onset. Focal seizures (96.1%) were more common than generalized seizures (3.9%). Fifty-three (51.5%) patients had an abnormal brain magnetic resonance imaging (MRI) scan. Among them, video-electroencephalogram findings in 31 (30.1%) patients correlated with MRI abnormalities. Levetiracetam was the most used drugs before admission, in hospital, and during follow-up. CONCLUSIONS: Autoimmune encephalitis is becoming an increasing risk factor of subsequent epilepsy in older people. Older patients with new epilepsy are more likely to respond to antiepileptic drugs, and drug-resistant epilepsy is uncommon.

Real-time TCD-vEEG monitoring for neurovascular coupling in epilepsy.

PURPOSE: Recently, a novel multi-model monitor has been available, which integrates real-time signals of transcranial Doppler (TCD) and video-EEG (vEEG) into one workstation. We sought to test the feasibility of this device in detecting neurovascular coupling in patients with epilepsy. METHOD: Cerebral blood flow velocity (CBFV) of bilateral middle cerebral arteries and vEEG during seizure episodes were recorded simultaneously in 12 patients (age 17-58 years) with partial epilepsies. The correlations between vEEG and CBFV findings were analyzed. RESULTS: Eleven seizure episodes were detected in 5 patients. Of them, bilateral CBFV increase with interhemispheric asymmetry was observed in 4 seizure episodes of 3 patients. EEG abnormalities preceded CBFV increase by 1-3s at the onset of a seizure. In a patient with bilateral middle cerebral artery stenosis, no apparent CBFV changes were detected during 2 of 3 seizure episodes. Another patient with previous frontal hemorrhage displayed CBFV increase without interhemispheric asymmetry during 4 seizure episodes. CONCLUSION: It is feasible to evaluate neurovascular coupling with good temporal correlation in patients with frequent seizure episodes by real-time TCD-vEEG monitoring.

Quick genetic screening using targeted next-generation sequencing in patients with tuberous sclerosis.

Tuberous sclerosis complex is an autosomal dominant disorder characterized by hamartomas in multiple organ systems. Mutations in the 2 large genes TSC1 and TSC2 have been demonstrated to be associated with tuberous sclerosis complex by various mutation screening methods. Targeted next-generation sequencing for genetic analysis is performed in the current study and is proved to be less cost, labor, and time consuming compared with Sanger sequencing. Two de novo and 1 recurrent TSC2 mutation in patients with tuberous sclerosis complex were revealed. Clinical details of patients were described and the underlying mechanism of the 2 novel TSC2 mutations, c.245G>A(p.W82X) and c.5405_5408dupACTT(p.P1803Lfs*25), were discussed. These results added to variability of TSC mutation spectrum and suggest that targeted next-generation sequencing could be the primary choice over Sanger sequencing in future tuberous sclerosis complex genetic counseling.

[Clinical analysis of 7 patients with Gerstmann syndrome secondary to cerebral vascular disease].

OBJECTIVE: To analyze clinical features of patients with Gerstmann syndrome (GS). METHODS: We retrospectively analysed the clinical manifestations of 7 patients (6 men and 1 woman) with GS secondary to cerebral vascular diseases and reviewed the literatures. RESULTS: The age ranged from 51 to 70 years with a mean of 70 years. They all had sudden onset and the tetrad of GS-finger agnosia, left-right disorientation, agraphia and acalculia, 3 patients accompanied by incomplete aphasia, 3 by anomic aphasia, 2 by alexia and 1 by constructional apraxia. Cranial computed tomographic scan showed low-density focus of the left parietal lobe in 6 cases and high-density focus of the left parietal lobe in 1 case. CONCLUSION: GS has the high value in localization and the lesion is mainly localized to angular gyrus of the dominant hemisphere.

Re-evaluation of PRRT2 mutations in paroxysmal disorders.

Mutations in PRRT2 have recently been identified as the major cause of autosomal dominant benign familial infantile epilepsy (BFIE), infantile convulsions with choreoathetosis syndrome (ICCA), and paroxysmal kinesigenic dyskinesia (PKD). Other paroxysmal disorders like febrile seizures, migraine, paroxysmal exercise-induced dyskinesia, and paroxysmal non-kinesigenic dyskinesia have also been shown to be associated with this gene. We re-evaluated PRRT2 mutations and genetic-clinical correlations in additional cases with PKD/ICCA and other paroxysmal disorders. Two novel mutations in PRRT2 were revealed in PKD/ICCA cases, while no mutations were detected in other diseases, which suggests BFIE and PKD are still core phenotypes of PRRT2-related spectrum disorders.