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. 2016 Mar 21;11(3):e0151667.
doi: 10.1371/journal.pone.0151667. eCollection 2016.

Spontaneously Fluctuating Motor Cortex Excitability in Alternating Hemiplegia of Childhood: A Transcranial Magnetic Stimulation Study

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Free PMC article

Spontaneously Fluctuating Motor Cortex Excitability in Alternating Hemiplegia of Childhood: A Transcranial Magnetic Stimulation Study

William M Stern et al. PLoS One. .
Free PMC article

Abstract

Background: Alternating hemiplegia of childhood is a very rare and serious neurodevelopmental syndrome; its genetic basis has recently been established. Its characteristic features include typically-unprovoked episodes of hemiplegia and other transient or more persistent neurological abnormalities.

Methods: We used transcranial magnetic stimulation to assess the effect of the condition on motor cortex neurophysiology both during and between attacks of hemiplegia. Nine people with alternating hemiplegia of childhood were recruited; eight were successfully tested using transcranial magnetic stimulation to study motor cortex excitability, using single and paired pulse paradigms. For comparison, data from ten people with epilepsy but not alternating hemiplegia, and ten healthy controls, were used.

Results: One person with alternating hemiplegia tested during the onset of a hemiplegic attack showed progressively diminishing motor cortex excitability until no response could be evoked; a second person tested during a prolonged bilateral hemiplegic attack showed unusually low excitability. Three people tested between attacks showed asymptomatic variation in cortical excitability, not seen in controls. Paired pulse paradigms, which probe intracortical inhibitory and excitatory circuits, gave results similar to controls.

Conclusions: We report symptomatic and asymptomatic fluctuations in motor cortex excitability in people with alternating hemiplegia of childhood, not seen in controls. We propose that such fluctuations underlie hemiplegic attacks, and speculate that the asymptomatic fluctuation we detected may be useful as a biomarker for disease activity.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Motor Evoked Potentials during the onset of a hemiplegic attack.
Consecutive MEPs during the onset of a hemiplegic attack (left panel) and following recovery, five minutes after the attack (right panel), in subject A2. Arrows represent latency of individual MEPs, dashed line represents average latency. During the onset of the attack (left panel), latency was variable, and amplitude decreased until no MEP was seen. Following recovery (right panel), amplitude and latency were stable. Stimulus strength was 130%rMT for all trials, which were performed at 5 second intervals.
Fig 2
Fig 2. Mean results for resting motor threshold and paired pulse paradigms.
Mean results for resting motor threshold (rMT), short interval intracortical inhibition (SICI), intracortical facilitation (ICF) and long interval intracortical inhibition (LICI) for people with alternating hemiplegia of childhood (AHC) and control subjects. There was a significant difference only in rMT (indicated by *, P = 0.002). Error bars show standard error.
Fig 3
Fig 3. Variability in Motor Evoked Potentials in people with AHC.
Each row shows two graphs of overlaid traces of 10 individual MEPs, performed using the same parameters, in the same subject, at different times during the same testing session. A change in MEP amplitude can be seen. In subject A2, there is also a change in MEP latency (average latency marked with an arrow).
Fig 4
Fig 4. Variability in stimulus-response curves in people with AHC.
Each graph shows two stimulus-response curves from the same subject, during the same testing session, demonstrating a change in cortical excitability. Subject 2 only tolerated testing of Right Motor Cortex, Subjects 3 and 4 were tested on both sides. P values given in the Fig were calculated using multivariate ANOVA comparing MEP size at Time 1 and Time 2, across stimulation intensities. Error bars show standard error.
Fig 5
Fig 5. Stimulus-response curves for ten control subjects with epilepsy, but not AHC.
Each graph shows two stimulus-response curves from the same subject, during the same testing session, demonstrating no significant change in cortical excitability. P values were calculated using multivariate ANOVA comparing MEP size at Time 1 and Time 2, across stimulation intensities. Error bars show standard error.
Fig 6
Fig 6. Stimulus-response curves for ten healthy control subjects.
Each graph shows two stimulus-response curves from the same subject, during the same testing session, demonstrating no significant change in cortical excitability. P values were calculated using multivariate ANOVA comparing MEP size at Time 1 and Time 2, across stimulation intensities. Error bars show standard error.

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Grant support

The study was funded by Epilepsy Society (UK) and undertaken at University College London Hospitals/University College London, which received a proportion of funding from the Department of Health’s National Institute for Health Research Biomedical Research Centres funding scheme. JWS is supported by the Marvin Weil Epilepsy Research Fund.

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