Prominent publications by Arn M J M van den Maagdenberg

KOL Index score: 13692

Sudden unexpected death in epilepsy (SUDEP) is a fatal complication of epilepsy in which brainstem spreading depolarization may play a pivotal role, as suggested by animal studies. However, patiotemporal details of spreading depolarization occurring in relation to fatal seizures have not been investigated. In addition, little is known about behavioural and neurophysiological features that may discriminate spontaneous fatal from non-fatal seizures. Transgenic mice carrying the missense ...

Known for Fatal Seizures |  Spreading Depolarization |  Cacna1as218l Mice |  Epilepsy Sudep |  Seizure Induced
KOL Index score: 13222

Trivial head trauma may be complicated by severe, sometimes even fatal, cerebral edema and coma occurring after a lucid interval ("delayed cerebral edema"). Attacks of familial hemiplegic migraine (FHM) can be triggered by minor head trauma and are sometimes accompanied by coma. Mutations in the CACNA1A calcium channel subunit gene on chromosome 19 are associated with a wide spectrum of mutation-specific episodic and chronic neurological disorders, including FHM with or without coma. We ...

Known for Minor Head Trauma |  Delayed Cerebral Edema |  Calcium Channel |  Cacna1a Gene |  Fatal Coma
KOL Index score: 13143

Migraine is an episodic neurovascular disorder that is clinically divided into two main subtypes that are based on the absence or presence of an aura: migraine without aura (MO) and migraine with aura (MA). Current molecular genetic insight into the pathophysiology of migraine predominantly comes from studies of a rare monogenic subtype of migraine with aura called familial hemiplegic migraine (FHM). Three FHM genes have been identified, which all encode ion transporters, suggesting that ...

Known for Migraine Aura |  Molecular Genetics |  Human Pair |  Fhm Genes |  Common Forms
KOL Index score: 13114

BACKGROUND: The R192Q mutation of the CACNA1A gene, encoding for the α1 subunit of voltage-gated P/Q Ca2+ channels (Ca(v)2.1), is associated with familial hemiplegic migraine-1. We investigated whether this gain-of-function mutation changed the structure and function of trigeminal neuron P2X3 receptors that are thought to be important contributors to migraine pain.

RESULTS: Using in vitro trigeminal sensory neurons of a mouse genetic model knockin for the CACNA1A R192Q mutation, we ...

Known for P2x3 Receptor |  Familial Hemiplegic |  Ganglion Neurons |  Mice Migraine |  Trigeminal Pain
KOL Index score: 12605

BACKGROUND: On trigeminal ganglion neurons, pain-sensing P2X3 receptors are constitutively inhibited by brain natriuretic peptide via its natriuretic peptide receptor-A. This inhibition is associated with increased P2X3 serine phosphorylation and receptor redistribution to non-lipid raft membrane compartments. The natriuretic peptide receptor-A antagonist anantin reverses these effects. We studied whether P2X3 inhibition is dysfunctional in a genetic familial hemiplegic migraine type-1 ...

Known for P2x3 Receptors |  Familial Hemiplegic Migraine |  Brain Natriuretic |  Mouse Model |  Trigeminal Sensory Neurons
KOL Index score: 12192

BACKGROUND: Familial hemiplegic migraine is an autosomal dominant severe subtype of migraine with aura characterised by some degree of hemiparesis during the attacks. So far, mutations in two genes regulating ion translocation-CACNA1A and ATP1A2-have been identified in pedigrees with this disease.

METHODS: To identify additional genes for familial hemiplegic migraine, we did a genome-wide linkage analysis of two disease pedigrees without mutations in CACNA1A and ATP1A2. Ion channel genes ...

Known for Sodium Channel |  Aura Mutation |  Hemiplegic Migraine |  Human Pair |  Fast Inactivation
KOL Index score: 12078

A knock-in (KI) mouse model of FHM-1 expressing the R192Q missense mutation of the Cacna1a gene coding for the α1 subunit of CaV2.1 channels shows, at the level of the trigeminal ganglion, selective functional up-regulation of ATP -gated P2X3 receptors of sensory neurons that convey nociceptive signals to the brainstem. Why P2X3 receptors are constitutively more responsive, however, remains unclear as their membrane expression and TRPV1 nociceptor activity are the same as in wildtype ...

Known for P2x3 Receptors |  Sensory Neurons |  Genetic Mouse Model |  Migraine Type |  Trigeminal Ganglion
KOL Index score: 11630

Migraine is a common disabling brain disorder. A subtype of migraine with aura (familial hemiplegic migraine type 1: FHM1) is caused by mutations in Ca(V)2.1 (P/Q-type) Ca(2+) channels. Knockin mice carrying a FHM1 mutation show increased neuronal P/Q-type current and facilitation of induction and propagation of cortical spreading depression (CSD), the phenomenon that underlies migraine aura and may activate migraine headache mechanisms. We studied cortical neurotransmission in neuronal ...

Known for Migraine Mice |  Spreading Depression |  Cortical Synapses |  Enhanced Excitatory Transmission |  Fhm1 Mutation
KOL Index score: 10923

BACKGROUND: Mutations in the gene ATP1A3 have recently been identified to be prevalent in patients with alternating hemiplegia of childhood (AHC2). Based on a large series of patients with AHC, we set out to identify the spectrum of different mutations within the ATP1A3 gene and further establish any correlation with phenotype.

METHODS: Clinical data from an international cohort of 155 AHC patients (84 females, 71 males; between 3 months and 52 years) were gathered using a specifically ...

Known for Atp1a3 Mutations |  Alternating Hemiplegia |  Clinical Profile |  Patients Ahc |  Asp801asn Mutation
KOL Index score: 10917

PURPOSE: Three forms of idiopathic partial epilepsy with autosomal dominant inheritance have been described: (a) autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE); (b) autosomal dominant lateral temporal epilepsy (ADLTE) or partial epilepsy with auditory features (ADPEAF); and (c) familial partial epilepsy with variable foci (FPEVF). Here we describe linkage analysis in a Dutch four-generation family with epilepsy fulfilling criteria of both ADNFLE and FPEVF.

METHODS: Clinical ...

Known for Partial Epilepsy |  Variable Foci |  Clinical Characteristics |  Human Pair |  Linkage Analysis
KOL Index score: 10858

Mutation S218L in the Ca(V)2.1 alpha(1) subunit of P/Q-type Ca(2+) channels produces a severe clinical phenotype in which typical attacks of familial hemiplegic migraine (FHM) triggered by minor head trauma are followed, after a lucid interval, by deep (even fatal) coma and long lasting severe cerebral edema. We investigated the functional consequences of this mutation on human Ca(V)2.1 channels expressed in human embryonic kidney 293 cells and in neurons from Ca(V)2.1 alpha(1)(-/-) mice ...

Known for Calcium Channels |  Familial Hemiplegic Migraine |  Mutation S218l |  Minor Head Trauma |  Cerebral Edema
KOL Index score: 10694

Migraine is a common, disabling, multifactorial, episodic neurovascular disorder of unknown etiology. Familial hemiplegic migraine type 1 (FHM-1) is a Mendelian subtype of migraine with aura that is caused by missense mutations in the CACNA1A gene that encodes the alpha(1) subunit of neuronal Ca(v)2.1 Ca(2+) channels. We generated a knockin mouse model carrying the human pure FHM-1 R192Q mutation and found multiple gain-of-function effects. These include increased Ca(v)2.1 current ...

Known for Increased Susceptibility |  Cortical Spreading |  Mouse Model |  Aura Migraine |  Ptype Calcium Channels
KOL Index score: 10609

Mutations in the CACNA1A gene are associated with neurological disorders, such as ataxia, hemiplegic migraine, and epilepsy. These mutations affect the pore-forming α(1A)-subunit of Ca(V)2.1 channels and thereby either decrease or increase neuronal Ca(2+) influx. A decreased Ca(V)2.1-mediated Ca(2+) influx has been shown to reduce the regularity of cerebellar Purkinje cell activity and to induce episodic cerebellar ataxia. However, little is known about how ataxia can be caused by ...

Known for Cerebellar Ataxia |  Purkinje Cell |  Calcium Channels |  S218l Mutation |  Mutant Mice
KOL Index score: 10592

Familial hemiplegic migraine (FHM) is a rare, severe, autosomal dominant subtype of migraine with aura. Up to 75% of FHM families have a mutation in the P/Q-type calcium channel Ca(v)2.1 subunit CACNA1A gene on chromosome 19p13. Some CACNA1A mutations also may cause epilepsy. Here, we describe novel missense mutations in the ATP1A2 Na(+),K(+)-ATPase pump gene on chromosome 1q23 in two families with FHM. The M731T mutation was found in a family with pure FHM. The R689Q mutation was ...

Known for Benign Familial |  Gene Atp1a2 |  Aura Mutation |  Infantile Convulsions |  Migraine Fhm
KOL Index score: 10477

Familial hemiplegic migraine type 1 (FHM1), a monogenic subtype of migraine with aura, is caused by gain-of-function mutations in CaV2.1 (P/Q-type) calcium channels. In FHM1 knockin mice, excitatory neurotransmission at cortical pyramidal cell synapses is enhanced, but inhibitory neurotransmission at connected pairs of fast-spiking (FS) interneurons and pyramidal cells is unaltered, despite being initiated by CaV2.1 channels. The mechanism underlying the unaltered GABA release at ...

Known for Synaptic Transmission |  Cav21 Channels |  Transgenic Migraine |  Fhm1 Mice |  Pyramidal Cells


Arn M J M van den Maagdenberg: Influence Statistics

Sample of concepts for which Arn M J M van den Maagdenberg is among the top experts in the world.
Concept World rank
p2x3 receptor responses #1
wt r192q cultures #1
calcium channels mutation #1
s218l missense mutation #1
myoclonic humans tremor #1
contribution inflammasome activation #1
knockin neurons #1
early stage gom #1
fhm1 mutation #1
fhm1 r192q #1
unaltered cortical #1
presynaptic cav21 #1
specific kinetic alterations #1
salt bridge lysine #1
mechanisms female preponderance #1
v1696i #1
cacna1a r583q #1
patients fhm1 mutation #1
s218l cortical #1
promotes deinhibition #1
fhm1 disorder #1
specific organs compartments #1
contribution inflammasomes #1
type cerebellar #1
endstage gom #1
histology capabilities #1
inactivation long depolarizations #1
constitutive hyperexcitability #1
headache genetics #1
ptype calcium channels #1
mutants g900r #1
17 activator od1 #1
knockin migraine #1
gwas migraine #1
migraine mutation carriers #1
transgenic migraine techniques #1
ctnnd2 morphologic abnormalities #1
migraine hemiplegic migraine #1
cav21 channel #1
r192q mutant #1
microprobe msi #1
morphologyassociated differences #1
microculture current density #1
channels fhm1 #1
mutants e174k #1
recurrent headache attacks #1
hyperexcitability phenotype migraine #1
mice migraine #1
fcmte phenotype #1
apnea brainstem seizures #1

Key People For Hemiplegic Migraine

Top KOLs in the world
Michel Dominique Ferrari
cluster headache migraine patients acute treatment
Gisela Marie Terwindt
cluster headache familial hemiplegic migraine retinal vasculopathy
Joost Haan
cluster headache hereditary cerebral hemorrhage familial hemiplegic migraine
cluster headache hemiplegic migraine cerebral vasoconstriction
Rune R Frants
familial hemiplegic migraine muscular dystrophy human pair
Elisabeth Tournier‐Lasserve
multiple sclerosis hemiplegic migraine cerebral cavernous malformations

Arn M J M van:Expert Impact

Concepts for whichArn M J M vanhas direct influence:Hemiplegic migraine,  Migraine aura,  Familial hemiplegic migraine,  Cluster headache,  Mutant mice,  Ptype calcium channels,  Cortical spreading depression,  Migraine type.

Arn M J M van:KOL impact

Concepts related to the work of other authors for whichfor which Arn M J M van has influence:Migraine aura,  Psychiatric disorders,  Animal models,  Chronic pain,  Cortical spreading depression,  Bipolar disorder,  Cluster headache.



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Department of Neurology, Leiden University Medical Centre, Leiden, Netherlands | Department of Human Genetics, Leiden University Medical Centre, Leiden, Netherlands | Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands

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