title: Spontaneously Fluctuating Motor Cortex Excitability in Alternating Hemiplegia of Childhood: A Transcranial Magnetic Stimulation Study.
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.
authors.affiliation: NIHR University College London Hospitals Biomedical Research Centre, Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, London, WC1N 3BG, United Kingdom.|Epilepsy Society, Chalfont St Peter, SL9 0RJ, United Kingdom.
authors.forename: William M
authors.initials: WM
authors.lastname: Stern
authors.affiliation: Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, London, United Kingdom.
authors.forename: Mahalekshmi
authors.initials: M
authors.lastname: Desikan
authors.affiliation: Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, London, United Kingdom.
authors.forename: Damon
authors.initials: D
authors.lastname: Hoad
authors.affiliation: MRC Centre for Neuromuscular Diseases, UCL Institute of Neurology, London, WC1N 3BG, United Kingdom.
authors.forename: Fatima
authors.initials: F
authors.lastname: Jaffer
authors.affiliation: Department of Translational Medicine, Section of Neurology, University of Piemonte Orientale "A. Avogadro", Novara, Italy.
authors.forename: Gionata
authors.initials: G
authors.lastname: Strigaro
authors.affiliation: NIHR University College London Hospitals Biomedical Research Centre, Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, London, WC1N 3BG, United Kingdom.|Epilepsy Society, Chalfont St Peter, SL9 0RJ, United Kingdom.|Stichting Epilepsie Instellingen Nederland (SEIN), Heemstede, Netherlands.
authors.forename: Josemir W
authors.initials: JW
authors.lastname: Sander
authors.affiliation: Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, London, United Kingdom.
authors.forename: John C
authors.initials: JC
authors.lastname: Rothwell
authors.affiliation: NIHR University College London Hospitals Biomedical Research Centre, Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, London, WC1N 3BG, United Kingdom.|Epilepsy Society, Chalfont St Peter, SL9 0RJ, United Kingdom.
authors.forename: Sanjay M
authors.initials: SM
authors.lastname: Sisodiya
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D019054:Evoked Potentials, Motor / Q000502:physiology; D005260:Female; D006429:Hemiplegia / Q000503:physiopathology*; D006801:Humans; D008297:Male; D009044:Motor Cortex / Q000502:physiology*; D009154:Mutation / Q000235:genetics; D050781:Transcranial Magnetic Stimulation; D055815:Young Adult