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1.
Proc Natl Acad Sci U S A. 2018 Aug 21;115(34):E8077-E8085. doi: 10.1073/pnas.1804764115. Epub 2018 Aug 3.

Selective NaV1.1 activation rescues Dravet syndrome mice from seizures and premature death.

Author information

1
Ion Channels and Disease Group, Florey Institute of Neuroscience and Mental Health, Parkville, VIC 3010, Australia.
2
Neuroscience Drug Discovery, H. Lundbeck A/S, DK-2500 Valby, Denmark.
3
Department of Drug Design and Pharmacology, Copenhagen University, DK-2100 Copenhagen, Denmark.
4
Sleep and Cognition Group, Epilepsy Division, Florey Insitute of Neuroscience and Mental Health, Parkville, VIC 3010, Australia.
5
Department of Pharmacology and Therapeutics, The University of Melbourne, Parkville, VIC 3010, Australia.
6
Centre for Advanced Imaging, The University of Queensland, Brisbane, QLD 4072, Australia.
7
Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia.
8
Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary.
9
Department of Medicine, The University of Melbourne, Parkville, VIC 3010, Australia.
10
Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia; glenn.king@imb.uq.edu.au spetrou@unimelb.edu.au.
11
Ion Channels and Disease Group, Florey Institute of Neuroscience and Mental Health, Parkville, VIC 3010, Australia; glenn.king@imb.uq.edu.au spetrou@unimelb.edu.au.

Abstract

Dravet syndrome is a catastrophic, pharmacoresistant epileptic encephalopathy. Disease onset occurs in the first year of life, followed by developmental delay with cognitive and behavioral dysfunction and substantially elevated risk of premature death. The majority of affected individuals harbor a loss-of-function mutation in one allele of SCN1A, which encodes the voltage-gated sodium channel NaV1.1. Brain NaV1.1 is primarily localized to fast-spiking inhibitory interneurons; thus the mechanism of epileptogenesis in Dravet syndrome is hypothesized to be reduced inhibitory neurotransmission leading to brain hyperexcitability. We show that selective activation of NaV1.1 by venom peptide Hm1a restores the function of inhibitory interneurons from Dravet syndrome mice without affecting the firing of excitatory neurons. Intracerebroventricular infusion of Hm1a rescues Dravet syndrome mice from seizures and premature death. This precision medicine approach, which specifically targets the molecular deficit in Dravet syndrome, presents an opportunity for treatment of this intractable epilepsy.

KEYWORDS:

Dravet syndrome; genetic epilepsy; seizures; spider venom; targeted drug therapy

PMID:
30076230
PMCID:
PMC6112713
DOI:
10.1073/pnas.1804764115
[Indexed for MEDLINE]
Free PMC Article
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3.
Seizure. 2018 Aug;60:184-189. doi: 10.1016/j.seizure.2018.06.022. Epub 2018 Jun 30.

Praxis-induced myoclonia: From the neurophysiologist to the patient perspective.

Author information

1
Unidade de Pesquisa e Tratamento das Epilepsias (UNIPETE), Universidade Federal de São Paulo (UNIFESP/EPM), São Paulo, SP, Brazil; Unidad de Epilepsia, Hospital Clínico San Carlos, Madrid, Spain; Neurología, Servicio de Medicina Interna, Hospital Universitario de Fuenlabrada, Madrid, Spain. Electronic address: belen.abarra@gmail.com.
2
Unidade de Pesquisa e Tratamento das Epilepsias (UNIPETE), Universidade Federal de São Paulo (UNIFESP/EPM), São Paulo, SP, Brazil. Electronic address: lucianamed36@gmail.com.
3
Unidade de Pesquisa e Tratamento das Epilepsias (UNIPETE), Universidade Federal de São Paulo (UNIFESP/EPM), São Paulo, SP, Brazil. Electronic address: mirian.guaranha@gmail.com.
4
Unidade de Pesquisa e Tratamento das Epilepsias (UNIPETE), Universidade Federal de São Paulo (UNIFESP/EPM), São Paulo, SP, Brazil. Electronic address: yacubian@terra.com.br.

Abstract

PURPOSE:

To characterize semiology and EEG features of praxis-induced (PI) myoclonia and to describe the subjective perception of juvenile myoclonic epilepsy (JME) patients with this reflex trait.

METHODS:

Patients with JME who presented myoclonia during a Video-EEG Neuropsychological Protocol were selected. We analyzed the semiology of upper limbs myoclonia and the ictal EEG patterns on Video-EEG. We explored the subjective aspects of PI by performing a semi-structured interview to each patient.

RESULTS:

15 patients experienced 59 upper limbs myoclonia. Jerks were more frequently asymmetric or unilateral (32/59); a bilaterally symmetric pattern of all myoclonia was observed in only five patients. Ictal pattern was polyspike-wave (PSW) in 31/59 myoclonic seizures and spike-and-wave (SW) in 28/59. Six patients started perceiving myoclonia while learning a new skill or practicing a previously learned skill in a more stressful context. For most patients, PI-myoclonia were a source of anxiety. PI persisted despite antiepileptic medications in 10 patients.

CONCLUSIONS:

Electroclinical features of PI-myoclonia were more heterogeneous than traditionally described. Ictal pattern of SW was almost as frequent as classical PSW. Patients described the influence of learning new skills and anxiety on PI. Their subjective perception let us understand the impact of this reflex trait.

KEYWORDS:

Anxiety comorbidity; Ictal patterns; Juvenile myoclonic epilepsy; Myoclonic seizures; Praxis induction; Video-EEG

PMID:
30025334
DOI:
10.1016/j.seizure.2018.06.022
[Indexed for MEDLINE]
Icon for Elsevier Science
4.
Seizure. 2018 Aug;60:144-148. doi: 10.1016/j.seizure.2018.06.023. Epub 2018 Jun 30.

Prospective study of the efficacy of a ketogenic diet in 20 patients with Dravet syndrome.

Author information

1
Department of Neurology, Children's Hospital of Fudan University, No. 399 wanyuan road, minhang district, Shanghai 201102, China. Electronic address: niyan6666@163.com.
2
Department of Neurology, Children's Hospital of Fudan University, No. 399 wanyuan road, minhang district, Shanghai 201102, China. Electronic address: xiner.1211@163.com.
3
Department of Neurology, Children's Hospital of Fudan University, No. 399 wanyuan road, minhang district, Shanghai 201102, China. Electronic address: linmeizhang@outlook.com.
4
Department of Neurology, Children's Hospital of Fudan University, No. 399 wanyuan road, minhang district, Shanghai 201102, China. Electronic address: acyimm@hotmail.com.
5
Department of Neurology, Children's Hospital of Fudan University, No. 399 wanyuan road, minhang district, Shanghai 201102, China. Electronic address: lwhhhhhh@126.com.
6
Department of Neurology, Children's Hospital of Fudan University, No. 399 wanyuan road, minhang district, Shanghai 201102, China. Electronic address: yuanfengzhou99@163.com.
7
Department of Neurology, Children's Hospital of Fudan University, No. 399 wanyuan road, minhang district, Shanghai 201102, China. Electronic address: szzhou@shmu.edu.cn.

Abstract

PURPOSE:

We evaluated the efficacy and tolerability of the ketogenic diet (KD) on generalised convulsions and status epilepticus (SE) in patients with Dravet syndrome (DS).

METHODS:

Patients with DS having ≥2 generalised convulsions/month despite drug treatment were included in this study and placed on a KD for 6 months. From 3 months before (baseline) to 6 months after KD initiation, caregivers recorded patients' seizure activity, antiepileptic drug use, and adverse events. The KD efficacy was determined by examining the frequency and duration of seizures at 3 and 6 months vs. baseline. Responders were defined as individuals whose generalised convulsions decreased in frequency by ≥50% vs. baseline. Seizures lasting ≥5 min and SE were specifically evaluated. Patients' cognition was also assessed at 3 and 6 months via questionnaire.

RESULTS:

Twenty patients continued the KD for at least 3 months. Of the 17 responders identified at month 3, seizures decreased by 50-89% and 90-99% in nine and two patients, respectively; six patients were seizure free. The KD was ineffective in three patients, who discontinued the diet. By month 6, seizures decreased by 50-89% and 90-99% in six and one patient(s), respectively; 10 patients were seizure free. The frequency of other seizure types also improved. During all 6 months, neither generalised convulsions lasting ≥5 min nor SE was detected in the 17 responders. The KD also improved patients' cognition.

CONCLUSION:

The KD is a good treatment option for medically intractable epilepsy.

KEYWORDS:

Dravet syndrome; Ketogenic diet; Refractory epilepsy; SCN1A

PMID:
29990707
DOI:
10.1016/j.seizure.2018.06.023
[Indexed for MEDLINE]
Icon for Elsevier Science
5.
Seizure. 2018 Aug;60:139-143. doi: 10.1016/j.seizure.2018.06.018. Epub 2018 Jun 28.

Modulation of epileptiform EEG discharges in patients with JME.

Author information

1
Department of Neurology, GIPMER, New Delhi, India. Electronic address: kamakshidhamija@gmail.com.
2
Department of Neurology, GIPMER, New Delhi, India.

Abstract

PURPOSE:

To study modulation of epileptiform EEG discharges in patients with JME.

METHOD:

50 subjects with JME underwent a sleep deprived EEG recording along with conventional provocative methods and testing with cognitive tasks (CTs). Both categories of tests were evaluated for their effect on occurrence of IEDs. Number of IEDs per unit time was calculated at baseline as well as with each task. Statistical and arbitrary methods were used to assess modulation. By arbitrary method if frequency of IEDs was more than twice that of baseline, it was considered as provocation and if less than half, it was considered as inhibition. To account for spontaneous fluctuation of IEDs, 95% CI was calculated for baseline IEDs in each patient and provocation/inhibition was considered if frequency of IEDs exceeded/remained below limits of CI respectively.

RESULTS:

There was no significant difference in rates of provocation of IEDs by conventional or CTs. However there was exclusive provocation of IEDs by CTs in 4 patients, 3 of whom were already on AEDs. There was a significant inhibitory effect of CTs as mean baseline discharge frequency was 0.4 ± 1.16 IEDS/min and during CTs was 0.1 ± 0.38 IEDs/min. However when spontaneous fluctuation was accounted for, inhibition was seen in only 22.23% patients by statistical method as compared to 90.91% by arbitrary method.

CONCLUSIONS:

Inclusion of CTs may assist in provocation of IEDs, thereby increasing yield of routine EEG. Spontaneous fluctuation of IEDs accounts for much observed inhibition by CTs in JME patients.

KEYWORDS:

Cognitive tasks; Juvenile myoclonic epilepsy

PMID:
29990706
DOI:
10.1016/j.seizure.2018.06.018
[Indexed for MEDLINE]
Icon for Elsevier Science
6.
Yonsei Med J. 2018 Aug;59(6):798-800. doi: 10.3349/ymj.2018.59.6.798.

First Molecular Diagnosis of a Patient with Unverricht-Lundborg Disease in Korea.

Author information

1
Department of Neurology, Epilepsy Research Institute, Yonsei University College of Medicine, Seoul, Korea.
2
Green Cross Genome, Yongin, Korea.
3
Green Cross Genome, Yongin, Korea. changski.md@gmail.com.
4
Department of Neurology, Epilepsy Research Institute, Yonsei University College of Medicine, Seoul, Korea. kheo@yuhs.ac.
#
Contributed equally

Abstract

Unverricht-Lundborg disease (ULD) is a form of progressive myoclonus epilepsy characterized by stimulation-induced myoclonus and seizures. This disease is an autosomal recessive disorder, and the gene CSTB, which encodes cystatin B, a cysteine protease inhibitor, is the only gene known to be associated with ULD. Although the prevalence of ULD is higher in the Baltic region of Europe and the Mediterranean, sporadic cases have occasionally been diagnosed worldwide. The patient described in the current report showed only abnormally enlarged restriction fragments of 62 dodecamer repeats, confirming ULD, that were transmitted from both her father and mother who carried the abnormally enlarged restriction fragment as heterozygotes with normal-sized fragments. We report the first case of a genetically confirmed patient with ULD in Korea.

KEYWORDS:

Progressive myoclonic epilepsy; Southern blot; Unverricht-Lundborg disease

PMID:
29978618
PMCID:
PMC6037595
DOI:
10.3349/ymj.2018.59.6.798
[Indexed for MEDLINE]
Free PMC Article
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7.
Int J Mol Sci. 2018 Jun 21;19(7). pii: E1825. doi: 10.3390/ijms19071825.

The Bacterial Protein CNF1 as a Potential Therapeutic Strategy against Mitochondrial Diseases: A Pilot Study.

Author information

1
Italian Center for Global Health, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, Italy. alessia.fabbri@iss.it.
2
Italian Center for Global Health, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, Italy. sara.travaglione@iss.it.
3
Italian Center for Global Health, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, Italy. zaira.maroccia@iss.it.
4
Department of Veterinary Public Health and Food Safety, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, Italy. marco.guidotti@iss.it.
5
Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, via Orabona, 4, 70124 Bari, Italy. ciroleopierri@gmail.com.
6
Unità di Neurofisiopatologia, Area Neuroscienze, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo Agostino Gemelli, 8, 00168 Rome, Italy. guido.primiano@gmail.com.
7
Unità di Neurofisiopatologia, Area Neuroscienze, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo Agostino Gemelli, 8, 00168 Rome, Italy. Serenella.Servidei@unicatt.it.
8
Italian Center for Global Health, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, Italy. stefano.loizzo@iss.it.
9
Italian Center for Global Health, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, Italy. carla.fiorentini@iss.it.

Abstract

The Escherichia coli protein toxin cytotoxic necrotizing factor 1 (CNF1), which acts on the Rho GTPases that are key regulators of the actin cytoskeleton, is emerging as a potential therapeutic tool against certain neurological diseases characterized by cellular energy homeostasis impairment. In this brief communication, we show explorative results on the toxin’s effect on fibroblasts derived from a patient affected by myoclonic epilepsy with ragged-red fibers (MERRF) that carries a mutation in the m.8344A>G gene of mitochondrial DNA. We found that, in the patient’s cells, besides rescuing the wild-type-like mitochondrial morphology, CNF1 administration is able to trigger a significant increase in cellular content of ATP and of the mitochondrial outer membrane marker Tom20. These results were accompanied by a profound F-actin reorganization in MERRF fibroblasts, which is a typical CNF1-induced effect on cell cytoskeleton. These results point at a possible role of the actin organization in preventing or limiting the cell damage due to mitochondrial impairment and at CNF1 treatment as a possible novel strategy against mitochondrial diseases still without cure.

KEYWORDS:

actin cytoskeleton; adenosine triphosphate; cytotoxic necrotizing factor 1; mitochondrial diseases; myoclonic epilepsy with ragged red fibers syndrome

PMID:
29933571
PMCID:
PMC6073533
DOI:
10.3390/ijms19071825
[Indexed for MEDLINE]
Free PMC Article
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8.
Seizure. 2018 Aug;60:68-70. doi: 10.1016/j.seizure.2018.06.010. Epub 2018 Jun 13.

The adult motor phenotype of Dravet syndrome is associated with mutation of the STXBP1 gene and responds well to cannabidiol treatment.

Author information

1
Department of Neurology, Spain. Electronic address: garinho29@icloud.com.
2
Department of Neurology, Spain. Electronic address: ayusta@sescam.jccm.es.

Abstract

Dravet syndrome is a terrible disease generally caused by mutations of the SCN1A gene. Recently others genes such as STXBP1 have been involved in the pathogenesis of the disease. The STXBP1 mutation in patients with Dravet Syndrome may additionally causes several parkinsonian features usually attributed to carriers of the SCN1A mutation. Management continues to be difficult that is why Cannabidiol emerged as valid option for treatment of this condition.

KEYWORDS:

Antecollis; Cannabidiol; Dravet syndrome; Parkinsonism; STXBP1; Seizures

PMID:
29929108
DOI:
10.1016/j.seizure.2018.06.010
[Indexed for MEDLINE]
Icon for Elsevier Science
9.
Epileptic Disord. 2018 Jun 1;20(3):195-199. doi: 10.1684/epd.2018.0978.

A case of perioral myoclonia with absences and its evolution in adulthood?

Author information

1
Health of Science University, Umraniye Education and Research Hospital, Department of Neurology, Istanbul.
2
Istanbul University, Cerrahpasa Medical Faculty, Department of Neurology, Istanbul, Turkey.

Abstract

The rare syndrome of perioral myoclonia with absences (POMA) is described as a specific type of idiopathic generalized epilepsy in which absence seizures are accompanied by prominent perioral myoclonus as a consistent symptom. We present a 52-year-old man who was referred to our department due to treatment-resistant epilepsy. Typical seizures were described as rhythmic twitching of the lips which started at six years old, and his first convulsive seizure occurred at around 20 years old. Based on video-EEG recordings, we present two distinct EEG patterns accompanied by slight differences in clinical manifestations, which appear to be atypical of POMA. Firstly, consciousness was preserved during seizures, with no manifestation of absences. Secondly, regarding the EEG features, in some of the seizures, the perioral motor symptoms were tonic rather than myoclonic. The defining features of POMA are discussed in relation to this case.

KEYWORDS:

clinical features; electrographic features; idiopathic (genetic) generalised epilepsy; perioral myoclonia with absences

PMID:
29905155
DOI:
10.1684/epd.2018.0978
[Indexed for MEDLINE]
Icon for John Libbey Eurotext
10.
Epileptic Disord. 2018 Jun 1;20(3):214-218. doi: 10.1684/epd.2018.0969.

Early-onset epileptic encephalopathy with myoclonic seizures related to 9q33.3-q34.11 deletion involving STXBP1 and SPTAN1 genes.

Author information

1
Division of Pediatric Neurology, Department of Neurology, Rutgers New Jersey Medical School, Newark, NJ, USA.
2
Department of Neurology, University of Rochester Medical Center, Rochester, NY, USA.

Abstract

We describe a 10-month-old boy with early-onset epileptic encephalopathy who was found to have a hemizygous deletion in 9q33.3-q34.11 involving STXBP1 and SPTAN1 genes. He presented at the age of 2.5 months with frequent upper extremity myoclonus, hypotonia, and facial dysmorphisms. Interictal EEG showed multifocal polyspike and wave during wakefulness and sleep. Ictal EEG revealed low-amplitude generalized sharp slow activity, followed by diffuse attenuation. Metabolic testing was unrevealing. Brain MRI showed thinning of the corpus callosum with an absence of rostrum. This patient is the second reported case with 9q33.3-q34.11 deletion involving STXBP1 and SPTAN1 genes associated with epileptic encephalopathy and myoclonic seizures. Larger case series are needed to better delineate this association.

KEYWORDS:

Early Infantile Epileptic Encephalopathy; Early Myoclonic Encephalopathy; Ohtahara syndrome; SPTAN1; STXBP1; encephalopathy; microdeletion

PMID:
29897043
DOI:
10.1684/epd.2018.0969
[Indexed for MEDLINE]
Icon for John Libbey Eurotext
11.
Handb Clin Neurol. 2018;155:143-174. doi: 10.1016/B978-0-444-64189-2.00010-X.

Spinocerebellar ataxias.

Author information

1
Department of Neurology, National Yang-Ming University Faculty of Medicine and Taipei Veterans General Hospital, Taipei, Taiwan. Electronic address: bwsoong@ym.edu.tw.
2
Department of Medical Genetics, Belfast HSC Trust, Belfast, United Kingdom.

Abstract

There are over 40 autosomal dominant spinocerebellar ataxias (SCAs) now identified. In this chapter we delineate the phenotypes of SCAs 1-44 and dentatorubral-pallidoluysian atrophy (DRPLA) and highlight the clinical and genetic features of the well characterised SCAs in detail in the main section of the chapter, along with their frequency and age at onset. We have included a section on the key phenotypic features of rare spinocerebellar ataxias and discuss rare and unusual presentations and genetic mechanisms of the ataxias and show differences between adult and paediatric presentations. We look at unusual mechanisms where knowledge is evolving in some dominant ataxias. For ease of reference we have tabulated historical aspects of the ataxias, major neurological diagnostic features, ataxias with predominant paediatric and infantile onset and list recognisable nerve conduction features. We comment on the anti-sense ataxia gene mechanisms and we discuss potential developments including exome sequencing and potential therapeutic options. A gene table listing all of the identified SCAs and DRPLA is also included with key references and gene locations and symbols with OMIM reference numbers for further reading.

KEYWORDS:

DRPLA; adult; ataxia; autosomal-dominant; cerebellar; pediatric; spinocerebellar; triplet repeat expansion

[Indexed for MEDLINE]
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12.
Neurol Sci. 2018 Sep;39(9):1565-1569. doi: 10.1007/s10072-018-3458-3. Epub 2018 Jun 2.

Expression analysis of beta-secretase 1 (BACE1) and its naturally occurring antisense (BACE1-AS) in blood of epileptic patients.

Author information

1
Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.
2
Department of Neurology, Hamadan University of Medical Sciences, Hamadan, Iran.
3
Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
4
Urogenital Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
5
Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran. mohammad_823@yahoo.com.
6
Urogenital Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. mohammad_823@yahoo.com.
7
Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran. s.ghafourifard@sbmu.ac.ir.
8
Urogenital Stem Cell Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. s.ghafourifard@sbmu.ac.ir.

Abstract

Beta-secretase 1 (BACE1) gene encodes a transmembrane protease from the peptidase A1 family of aspartic proteases whose role in the pathogenesis of Alzheimer's disease has been assessed. The enzymatic activity of BACE1 on several proteins implicated in epileptogenesis implies its role in the pathogenesis of epilepsy. In the present study, we assessed expression of BACE1 and its naturally occurring antisense (BACE1-AS) in peripheral blood of 40 epileptic patients and 40 age- and sex-matched healthy subjects. We did not detect either any difference in the expression of these genes between cases and controls or significant correlation between their expressions and participants' age. However, we demonstrated a significant correlation between expression levels of BACE1 and BACE1-AS which supports the previously suggested feed-forward mechanism of regulation between these two transcripts. Future studies in larger sample sizes are needed to elaborate the function of BACE1 in epilepsy.

KEYWORDS:

BACE1; BACE1-AS; Epilepsy

PMID:
29860633
DOI:
10.1007/s10072-018-3458-3
[Indexed for MEDLINE]
Icon for Springer
13.
Expert Opin Investig Drugs. 2018 Jun;27(6):535-541. doi: 10.1080/13543784.2018.1482275. Epub 2018 Jun 6.

Investigational cannabinoids in seizure disorders, what have we learned thus far?

Author information

1
a Faculty of Medical Sciences , University of Kragujevac , Kragujevac , Serbia.

Abstract

The anticonvulsant activity of cannabinoids attracted much attention in the last decade. Cannabinoids that are currently investigated with the intention of making them drugs for the treatment of epilepsy are cannabidiol, cannabidivarin, Δ9-tetrahydrocannabivarin, and Δ9-tetrahydrocannabinolic acid. Areas covered:In this review, the authors look at the results of preclinical and clinical studies with investigational cannabinoids. Relevant literature was searched for in MEDLINE, SCOPUS, EBSCO, GOOGLE SCHOLAR, and SCINDEX databases. Expert opinion: Preclinical studies confirmed anticonvulsant activity of cannabidiol and cannabidivarin in a variety of epilepsy models. While the results of clinical trials with cannabidivarin are still awaited, cannabidiol showed clear therapeutic benefit and good safety in patients with therapy-resistant seizures associated with Dravet syndrome and in patients with Lennox-Gastaut syndrome who have drop seizures. However, the full therapeutic potential of cannabinoids in treatment-resistant epilepsy needs to be investigated in the near future.

KEYWORDS:

Cannabidiol; Dravet syndrome; Lennox–Gastaut syndrome; cannabidivarin; treatment-resistant epilepsy

PMID:
29842819
DOI:
10.1080/13543784.2018.1482275
[Indexed for MEDLINE]
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14.
Seizure. 2018 Jul;59:116-122. doi: 10.1016/j.seizure.2018.05.015. Epub 2018 May 20.

Relapse after treatment withdrawal of antiepileptic drugs for Juvenile Absence Epilepsy and Juvenile Myoclonic Epilepsy.

Author information

1
School of Medicine, University of Nottingham, Nottingham, NG7 2UH, United Kingdom.
2
Department of Paediatric Neurology, Nottingham Children's Hospital, Nottingham University Hospitals NHS Trust, Nottingham, NG7 2UH, United Kingdom.
3
Department of Neurology, Nottingham University Hospitals NHS Trust, Nottingham, NG7 2UH, United Kingdom.
4
School of Medicine, University of Nottingham, Nottingham, NG7 2UH, United Kingdom; Department of Paediatric Neurology, Nottingham Children's Hospital, Nottingham University Hospitals NHS Trust, Nottingham, NG7 2UH, United Kingdom. Electronic address: william.whitehouse@nottingham.ac.uk.

Abstract

PURPOSE:

Conventional teaching is that juvenile myoclonic epilepsy (JME) and juvenile absence epilepsy (JAE) require lifelong antiepileptic drug (AED) treatment. We therefore wanted to determine how many patients attending our epilepsy service with JAE or JME went into 2 year remission, and then relapsed, both off and on AEDs.

METHOD:

This was a retrospective case-notes review. Patients with JAE and JME were systematically ascertained from clinic lists and databases at one teaching hospital. Data was extracted systematically. Simple descriptive statistics were used.

RESULTS:

JAE: 14/36 (39%) were seizure free on AEDs for at least 2 years. Of the 6 (43%) attempting AED withdrawal, all (100%) relapsed, compared with only 25% of those who did not withdraw AEDs. Only 2/5 who relapsed and restarted AEDs regained remission. JME: 32/145 (22%) were seizure free on AEDs for at least 2 years. Of the 10 (31%) attempting AED withdrawal, 8 (80%) relapsed, compared with only 36% of those who did not withdraw AEDs. Only 2/8 who relapsed and restarted AEDs regained remission.

CONCLUSION:

Remission rates for JAE and JME was lower than expected. Higher proportions of seizure free patients underwent physician-supervised withdrawal than anticipated. Relapse rates off AEDs were similar for JAE and JME, and at least twice as high as for those remaining on AEDs, and a further remission was not invariable on restarting AEDs. Our experience, comparing relapse in those withdrawing to those staying on AEDs will help in discussions with patients keen to try AED withdrawal.

KEYWORDS:

Absence seizures; Adolescent; Adult; Antiepileptic drugs; Generalised seizures; Juvenile; Myoclonic epilepsy

PMID:
29807291
DOI:
10.1016/j.seizure.2018.05.015
[Indexed for MEDLINE]
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15.
Value Health. 2018 May;21(5):501-507. doi: 10.1016/j.jval.2018.03.002. Epub 2018 Apr 5.

The Problem of Rarity: Estimation of Prevalence in Rare Disease.

Author information

1
Service de Neurologie Pédiatrique, Université Paris Diderot, Paris, France. Electronic address: stephane.auvin@aphp.fr.
2
Zogenix International Ltd., Maidenhead, Berkshire, UK.
3
Wickenstones, Oxfordshire, UK.

Abstract

BACKGROUND:

From a disease's first description to its wider recognition, factors such as changes over time in diagnostic criteria, available therapies, and subsequent mortality rates may influence diagnosed prevalence of rare diseases.

OBJECTIVES:

To propose a novel methodology for estimating the true prevalence of rare diseases using current incidence adjusted to changing diagnostic practice over time. This article focuses on rare diseases whose diagnosis may have changed over time, and raises the hypothesis that prevalence calculated from current incidence may be higher than diagnosed prevalence, which may lag behind the current disease definition and diagnostic methods. A rare epileptic encephalopathy, Dravet syndrome (DS), is explored as an illustrative example.

METHODS:

A targeted literature review was performed for DS to identify all reported incidence, prevalence, and mortality and depict how diagnostic practice has evolved over time. A conceptual model was developed to calculate prevalence derived from current incidence figures alone (incidence-derived prevalence) or incidence adjusted with factors that cause a diagnostic drag (diagnostic awareness-adjusted prevalence).

RESULTS:

We identified sufficient publications of incidence and prevalence to test the conceptual model. For pediatric patients with DS, diagnosed prevalence in the field (as reported in current literature) matches incidence-derived prevalence, whereas for adult patients, it is overestimated by incidence-derived prevalence, but not by diagnostic awareness-adjusted prevalence.

CONCLUSIONS:

Care should be taken with current incidence-derived prevalence figures to not overstate the prevalence in rare diseases, as methodological challenges in counting small populations, coupled with advances in rare disease discovery, may cause discrepancies.

KEYWORDS:

Dravet syndrome; epidemiology; incidence; prevalence; rare disease

PMID:
29753345
DOI:
10.1016/j.jval.2018.03.002
[Indexed for MEDLINE]
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16.
Seizure. 2018 Jul;59:11-15. doi: 10.1016/j.seizure.2018.04.013. Epub 2018 Apr 23.

Tap seizures in infancy: A critical review.

Author information

1
Child Neuropsychiatric Unit, Maternal and Child Health Department, Parma University-Hospital, Parma, Italy.
2
Child Neuropsychiatric Unit, Neuroscience Department, University of Parma, Parma, Italy. Electronic address: anna.andreolli@studenti.unipr.it.
3
Child Neuropsychiatric Unit, Neuroscience Department, University of Parma, Parma, Italy.

Abstract

Tap seizure is a type of reflex myoclonic epilepsy in which seizures are evoked mainly by unexpected tactile stimuli and which is classified among the electroclinical syndromes of infancy. This condition, whose onset is in the first two years of life, is characterized by excellent prognosis and is extremely rare. We reviewed all published articles and case reports on Reflex Myoclonic Epilepsies focusing on touch-induced seizures in order to clarify clinical and electroencephalographic findings. Our aim is to increase knowledge about this specific disorder in order to help pediatricians avoid extensive investigations when making their diagnosis and reassure parents regarding absence of long-term complications.

KEYWORDS:

Reflex Myoclonic Epilepsy of Infancy; Reflex seizure with somatosensory precipitation; Tap epilepsy; Tap seizures; Touch evoked seizure

PMID:
29727740
DOI:
10.1016/j.seizure.2018.04.013
[Indexed for MEDLINE]
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18.
Medicine (Baltimore). 2018 Apr;97(15):e0299. doi: 10.1097/MD.0000000000010299.

Occipital epilepsy versus progressive myoclonic epilepsy in a patient with continuous occipital spikes and photosensitivity in electroencephalogram: A case report.

Author information

1
Department of Neurology and Neuroscience Center, The First Hospital of JiLin University, Changchun.
2
Department of Neurology, Yidu Central Hospital, Weifang, Shandong, China.

Abstract

INTRODUCTION:

Progressive myoclonic epilepsy (PME) is rare epilepsy syndrome. Although EEG is a useful neurophysiological technique in the evaluation of epilepsy, few EEG abnormalities have been described in PME. So, how to use EEG hints to establish the suspected diagnosis of PME as soon as possible should be addressed.

CASE PRESENT:

We presented a case with refractory myoclonic seizures, and progressive neurological deterioration, diagnosed as PME and neuronal ceroid lipofuscinosis disease by gene testing. The patient manifested with a significant regression in her speech ability and motor balance. The mini-mental state examination showed poor scores of 15/30. The magnetic resonance imaging showed diffused atrophy. Her EEG showed slow background with continuous occipital small spikes and photosensitivity. The following genetic testing with mutation in CLN6 confirmed the diagnosis and excluded the occipital epilepsy.

CONCLUSION:

Our case showed rare manifestations and special EEG features of PME, which may be confused with occipital epilepsy or photosensitive epilepsy. Thus, if the continuous occipital spikes and photosensitivity were presented in a patient with refractory seizures and developmental regression, PME should be considered.

PMID:
29642155
PMCID:
PMC5908557
DOI:
10.1097/MD.0000000000010299
[Indexed for MEDLINE]
Free PMC Article
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19.
Biochem Biophys Res Commun. 2018 Jun 2;500(2):158-162. doi: 10.1016/j.bbrc.2018.04.009. Epub 2018 Apr 13.

Myoclonus epilepsy, retinitis pigmentosa, leukoencephalopathy and cerebral calcifications associated with a novel m.5513G>A mutation in the MT-TW gene.

Author information

1
Department of Medicine, Surgery and Neuroscience, University of Siena, Viale Bracci 2, 53100, Siena, Italy. Electronic address: cardaioli@unisi.it.
2
Department of Medicine, Surgery and Neuroscience, University of Siena, Viale Bracci 2, 53100, Siena, Italy.
3
Perugia Hospital, Neurophysiopathology Unit, Azienda Ospedaliera di Perugia, S. Andrea delle Fratte, 06156 Perugia, Italy.
4
Molecular Medicine, IRCCS Stella Maris, Via dei Giacinti 2, 56128, Pisa, Italy.
5
Department of Translational Research & The New Technologies in Medicine & Surgery, University of Pisa, Via Paradisa 2, 56124, Pisa, Italy.

Abstract

We sequenced the mitochondrial genome from a 40-year-old woman with myoclonus epilepsy, retinitis pigmentosa, leukoencephalopathy and cerebral calcifications. Histological and biochemical features of mitochondrial respiratory chain dysfunction were present. Direct sequencing showed a novel heteroplasmic mutation at nucleotide 5513 in the MT-TW gene that encodes tRNATrp. Restriction Fragment Length Polymorphism analysis confirmed that about 80% of muscle mtDNA harboured the mutation while it was present in minor percentages in mtDNA from other tissues. The mutation is predicted to disrupt a highly conserved base pair within the aminoacyl acceptor stem of the tRNA. This is the 17° mutation in MT-TW gene and expands the known causes of late-onset mitochondrial diseases.

KEYWORDS:

MT-TW gene; Mitochondrial disease; New mutation; mtDNA; tRNA(Trp)

PMID:
29625105
DOI:
10.1016/j.bbrc.2018.04.009
[Indexed for MEDLINE]
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20.
Seizure. 2018 Apr;57:80-86. doi: 10.1016/j.seizure.2018.03.015. Epub 2018 Mar 14.

Progressive myoclonus epilepsy without renal failure in a Chinese family with a novel mutation in SCARB2 gene and literature review.

Author information

1
Department of Neurology and Institute of Neurology, Rui Jin Hospital & Rui Jin Hospital North, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: taat@sjtu.edu.cn.
2
Department of Neurology and Institute of Neurology, Rui Jin Hospital & Rui Jin Hospital North, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Department of Neurology, Shanghai Fengxian District Central Hospital, Shanghai Jiao Tong University Affiliated Sixth People's Hospital South Campus, Shanghai, 201406, China. Electronic address: 1127209141@sjtu.edu.cn.
3
Department of Neurology and Institute of Neurology, Rui Jin Hospital & Rui Jin Hospital North, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: xuyangqi4362186@sjtu.edu.cn.
4
Department of Neurology and Institute of Neurology, Rui Jin Hospital & Rui Jin Hospital North, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: shirley_xjh@hotmail.com.
5
Department of Neurology and Institute of Neurology, Rui Jin Hospital & Rui Jin Hospital North, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: zhaiyan.com@163.com.
6
Department of Neurology and Institute of Neurology, Rui Jin Hospital & Rui Jin Hospital North, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: wang-ying@medmail.com.cn.
7
Department of Neurology and Institute of Neurology, Rui Jin Hospital & Rui Jin Hospital North, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: thd10495@rjh.com.cn.
8
Department of Neurology and Institute of Neurology, Rui Jin Hospital & Rui Jin Hospital North, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: ruijincsd@126.com.
9
Department of Neurology and Institute of Neurology, Rui Jin Hospital & Rui Jin Hospital North, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: luanxinghua@bjmu.edu.cn.
10
Department of Neurology and Institute of Neurology, Rui Jin Hospital & Rui Jin Hospital North, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: caoli2000@yeah.net.

Abstract

PURPOSE:

To describe the clinical and genetic features of a Chinese progressive myoclonus epilepsy (PME) patient related with SCARB2 mutation without renal impairment and review 27 SCARB2-related PME patients from 11 countries.

METHODS:

The patient was a 27-year-old man with progressive action myoclonus, ataxia, epilepsy, dysarthria and absence of cognitive deterioration. Renal functional test was normal. Electroencephalography (EEG) showed progressively slowed background activity and sporadic generalized spike-and-wave discharges. Electromyography (EMG) showed slowed motor and sensory nerve conduction velocities and distal motor latency delay accompanied by normal compound motor action potential (CMAP) and amplitudes of sensory nerve action potential (SNAP). The amplitude of cortical components of brainstem auditory-evoked potential (BAEP) was normal with slightly prolonged latencies. Generalized atrophy, ventricle enlargement and white matter degeneration was observed in brain magnetic resonance imaging (MRI). Open muscle biopsy and genetic analysis were performed. Two hundred healthy individuals were set for control. Quantitative real time PCR (qPCR), western blotting and immunofluorescence were carried out to evaluate the fate of the SCARB2 mRNA and lysosomal-membrane type 2 (LIMP2) protein level.

RESULTS:

One homozygous mutation in SCARB2 gene (c.1187 + 5G > T) was identified in the patient. Each of his parents carried a heterozygous variant. This mutation was not detected among the healthy controls and predicted to be damaging or disease causing by prediction tools. qPCR revealed a significantly lower level of SCARB2 mRNA in peripheral blood cell of the proband compared with his parents and healthy control individuals. Muscle biopsy showed mild variation in fiber size. Western blotting and immunofluorescence detected an extremely weak signal of LIMP2 protein from skeletal muscle of the proband.

CONCLUSION:

In this study, we identified a SCARB2-related PME patient with normal renal function and a novel homozygous splicing mutation. SCARB2 gene should be analyzed in patients with progressive action myoclonus, epilepsy, peripheral neuropathy, without cognitive deterioration or renal failure.

KEYWORDS:

Action myoclonus renal failure syndrome; Peripheral neuropathy; Progressive myoclonus epilepsy; SCARB2

PMID:
29605618
DOI:
10.1016/j.seizure.2018.03.015
[Indexed for MEDLINE]
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