The edition · Neurology
Lamotrigine levels fall by two-thirds by the third trimester, and treating amyloid neuropathy early beats treating it well
A 947-woman Chinese cohort quantifies how far each antiseizure drug drops in pregnancy, CSF amyloid tracks the severity of cerebral amyloid angiopathy better than microbleed counts, and plasma p-tau217 explains part of the cognitive decline in late-onset unexplained epilepsy.
The edition in brief
In a prospective multicentre Chinese cohort of 947 women with epilepsy contributing 1,638 samples, concentration-to-dose ratios fell steeply in pregnancy. Lamotrigine dropped 28.8%, 54.3% and 63.2% across the three trimesters, reaching a nadir of -65.8% at 32 weeks. Levetiracetam fell 26.2%, 40.1% and 31.0%, with a nadir of -35.5% at 24 weeks; the oxcarbazepine metabolite fell 23.1%, 32.6% and 44.3%; lacosamide fell 10.8% in the second trimester. Concomitant drugs shifted baseline ratios without changing the gestational trajectory, and interindividual variability dominated everything measured. In 102 patients with probable cerebral amyloid angiopathy by Boston criteria v2.0, lower CSF amyloid-beta 40 and 42 were associated with greater cortical superficial siderosis (standardised beta -0.49 and -0.42) and higher Fazekas score, but not with lobar microbleed count. Tau species showed no association with any MRI marker, and the findings held after stratifying by an Alzheimer-like amyloid profile. Among 85 people with late-onset unexplained epilepsy, higher plasma p-tau217 was associated with poorer cognition (beta -0.66, 95% CI -1.19 to -0.13), worst in those with medication-refractory epilepsy. About 24% of that association was accounted for by reduced spindle-slow oscillation coupling on sleep EEG. A double-blind sham-controlled trial of dual transcranial direct current stimulation in 74 patients with post-stroke cognitive impairment improved Montreal Cognitive Assessment scores by 5.74 points against 2.69 with sham. A post hoc analysis of NEURO-TTRansform found eplontersen maintained neuropathy scores across all baseline severity tertiles, while historical placebo worsened.
By 32 weeks, a lamotrigine dose is doing a third of the work it did before pregnancy
Lamotrigine concentration-to-dose ratios fall by about two-thirds by 32 weeks and levetiracetam by about a third by 24 weeks, so measure each trimester and titrate against the woman's own preconception level.
In cerebral amyloid angiopathy, CSF amyloid tracks the siderosis rather than the microbleeds
Lower CSF amyloid-beta tracked cortical superficial siderosis and white matter burden in cerebral amyloid angiopathy but not microbleed count, so siderosis is the better severity marker on the scan you already have.
In late-onset epilepsy of no clear cause, sleep spindles carry part of the cognitive decline
In late-onset unexplained epilepsy, higher plasma p-tau217 was associated with worse cognition, especially with refractory seizures, so assess cognition and sleep rather than attributing decline to medication.
Prefrontal tDCS improved cognition after stroke, in 74 patients
Dual prefrontal transcranial direct current stimulation improved Montreal Cognitive Assessment scores by about three points over sham after stroke, but on 74 patients with no reported follow-up beyond treatment.
Write the postpartum dose reduction on the same prescription as the increase
Write the postpartum taper on the same prescription as the antenatal dose increase, with a dated plan in the woman's hand and a booked level - otherwise the raised dose stays after the levels have returned.
Eplontersen held neuropathy scores steady whatever the starting severity, which is an argument for starting early
Eplontersen maintained neuropathy, quality of life and nutritional scores across every baseline severity tertile in hereditary transthyretin amyloidosis, so treat early - the function preserved is the function the patient still has.
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