Annals of neurology
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Annals of neurology · Jul 2013
Pain referral patterns of the C1 to C3 nerves: implications for headache disorders.
The cervical nerves may play a significant role in primary headache disorders. We reviewed the patterns of pain evoked by stimulation of the first 3 cervical nerves (C1-C3) in 10 patients with chronic occipital pain, 6 of whom also had migraine. ⋯ C2 and C3 stimulation resulted in occipital or cervical pain in all patients. The C1 nerve may have an important sensory function in headache disorders that have orbital and frontal pain as a prominent feature.
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Annals of neurology · Jul 2013
Nonconvulsive seizures after subarachnoid hemorrhage: Multimodal detection and outcomes.
Seizures have been implicated as a cause of secondary brain injury, but the systemic and cerebral physiologic effects of seizures after acute brain injury are poorly understood. ⋯ We replicated in humans complex physiologic processes associated with seizures after acute brain injury previously described in laboratory experiments and illustrated differences such as the delayed increase in rCBF. These real world physiologic observations may permit more successful translation of laboratory research to the bedside.
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Annals of neurology · Jul 2013
Dravet syndrome patient-derived neurons suggest a novel epilepsy mechanism.
Neuronal channelopathies cause brain disorders, including epilepsy, migraine, and ataxia. Despite the development of mouse models, pathophysiological mechanisms for these disorders remain uncertain. One particularly devastating channelopathy is Dravet syndrome (DS), a severe childhood epilepsy typically caused by de novo dominant mutations in the SCN1A gene encoding the voltage-gated sodium channel Na(v) 1.1. Heterologous expression of mutant channels suggests loss of function, raising the quandary of how loss of sodium channels underlying action potentials produces hyperexcitability. Mouse model studies suggest that decreased Na(v) 1.1 function in interneurons causes disinhibition. We aim to determine how mutant SCN1A affects human neurons using the induced pluripotent stem cell (iPSC) method to generate patient-specific neurons. ⋯ These data demonstrate that epilepsy patient-specific iPSC-derived neurons are useful for modeling epileptic-like hyperactivity. Our findings reveal a previously unrecognized cell-autonomous epilepsy mechanism potentially underlying DS, and offer a platform for screening new antiepileptic therapies.
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Annals of neurology · Jul 2013
Clinical correlates in an experimental model of repetitive mild brain injury.
Although there is growing awareness of the long-term cognitive effects of repetitive mild traumatic brain injury (rmTBI; eg, sports concussions), whether repeated concussions cause long-term cognitive deficits remains controversial. Moreover, whether cognitive deficits depend on increased amyloid β deposition and tau phosphorylation or are worsened by the apolipoprotein E4 allele remains unknown. Here, we use an experimental model of rmTBI to address these clinical controversies. ⋯ Within the vulnerable time period between injuries, rmTBI produces long-term cognitive deficits independent of increased amyloid β or tau phosphorylation. In this model, cognitive outcome is not influenced by APOE4 status. The data have implications for the long-term mental health of athletes who suffer multiple concussions.