Annals of neurology
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Annals of neurology · Dec 2015
Case ReportsQuinidine in the treatment of KCNT1 positive epilepsies.
We report 2 patients with drug-resistant epilepsy caused by KCNT1 mutations who were treated with quinidine. Both mutations manifested gain of function in vitro, showing increased current that was reduced by quinidine. ⋯ The other, who had a novel phenotype, with severe nocturnal focal and secondary generalized seizures starting in early childhood with developmental regression, did not improve. Although quinidine represents an encouraging opportunity for therapeutic benefits, our experience suggests caution in its application and supports the need to identify more targeted drugs for KCNT1 epilepsies.
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Annals of neurology · Nov 2015
Elevated synchrony in Parkinson disease detected with electroencephalography.
Parkinson disease (PD) can be difficult to diagnose and treat. Development of a biomarker for PD would reduce these challenges by providing an objective measure of disease. Emerging theories suggest PD is characterized by excessive synchronization in the beta frequency band (∼20Hz) throughout basal ganglia-thalamocortical loops. Recently we showed with invasive electrocorticography that one robust measure of this synchronization is the coupling of beta phase to broadband gamma amplitude (ie, phase-amplitude coupling [PAC]). Other recent work suggests that high-frequency activity is detectable at the scalp using electroencephalography (EEG). Motivated by these findings, we tested whether beta-gamma PAC over sensorimotor cortex, recorded noninvasively with EEG, differs between PD patients off and on medications, and healthy control subjects. ⋯ Elevated PAC is detectable using scalp EEG in PD patients off medications compared to on medications, and compared to healthy controls. This suggests that EEG PAC may provide a noninvasive biomarker of the parkinsonian state. This biomarker could be used as a control signal for closed-loop control of deep brain stimulation devices, for adjustment of dopaminergic treatment, and also has the potential to aid in diagnosis.
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Annals of neurology · Nov 2015
Genome-wide variant by serum urate interaction in Parkinson's disease.
Serum urate levels have been associated with risk for and progression of Parkinson's disease (PD). Urate-related compounds are therapeutic candidates in neuroprotective efforts to slow PD progression. A urate-elevating agent is currently under investigation as a potential disease-modifying strategy in people with PD. However, PD is a heterogeneous disorder, and genetic variation may explain divergence in disease severity and progression. ⋯ Genetic profile combined with serum urate level can be used to predict disease severity and potential disease progression in patients with PD. These results may be relevant to therapeutic efforts targeting the urate pathway.
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Annals of neurology · Oct 2015
Review Case ReportsProgressive neurologic dysfunction in a psoriasis patient treated with dimethyl fumarate.
Progressive multifocal leukoencephalopathy (PML) has recently been described in psoriasis or multiple sclerosis patients treated with fumaric acid esters (fumarates), who had developed severe and long-standing lymphocytopenia (<500/mm(3) ). We report a psoriasis patient who presented with progressive neurologic dysfunction and seizures after 2.5 years of fumarate therapy. ⋯ Brain biopsy revealed typical features of PML as well as JC virus-infected neurons. Clinicians should consider PML in the differential diagnosis of fumarate-treated patients presenting with brain lesions or seizures even in the absence of severe lymphocytopenia.
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We aimed to investigate the roles of different resting-state networks in predicting both the actual level of consciousness and its recovery in brain injury patients. ⋯ Our findings show that SN (SACC-LAI) connectivity correlates with behavioral signs of consciousness, whereas DMN (PCC-LLPC) connectivity instead predicts recovery of consciousness.