there is strong epidemiological and genetic evidence that genetic factors play a major , though variable role , in its pathogenesis .
migraine patients are characterized between attacks on various cns - evoked responses by a deficit of habituation [ 1 , 2 ] , which may have a familial character [ 35 ] .
by contrast , other mild abnormalities have been identified that are unlikely to play a pathogenic role : a decreased safety factor at the neuromuscular junction on single fiber emg ( sfemg ) [ 79 ] and subclinical cerebellar hypermetria in the horizontal plane on opto - electronic analysis of upper arm - reaching movements .
if this is correct , one may expect that in the same individual they be of a similar degree .
we have therefore compared in the same migraine patient the sfemg and 3d - movement analysis .
thirteen migraine patients ( ichd - ii )   were recruited from the headache clinic of the headache research unit in lige , belgium .
eight patients suffering from typical aura with migraine headache ( mta  ichd - ii code 1.2.1 ; three women and five men ; median age 28.5  years ; range 1367 ) and five patients with migraine without aura ( mo  ichd - ii code 1.1 ; three women and two men ; median age 40.0  years ; range 3151 ) underwent both stimulation - sfemg and 3d - movement analysis .
none of them had any other medical condition detectable by history and clinical examination ; none was taking drugs on a regular basis , nor had taken any drug within 3  days before the recordings .
the recordings took place at least 3  days after and before an attack ( checked by telephone - interview ) .
the study was conducted after approval of our institution s ethics committee and performed in accordance with the ethical standards of the 1964 declaration of helsinki , with the understanding and consent of each involved subject .
a nicolet viking iv device ( nicolet biomedical , madison , wisconsin , usa ) was used for stimulation single fiber electromyography .
single muscle fiber activity was recorded with 25-mm - long single fiber needles ( medelec neurodiagnostic accessories , ref : 16829 , witney , oxfordshire , uk ) , and the motor nerve was stimulated with nicolet teflon - insulated monopolar needles .
we stimulated suprathreshold the motor branch of the radial nerve and assessed the variability in latency , i.e. the jitter ( fig .  1 ) , of single fiber action potentials in m. extensor digitorum communis ( edc ) of the right arm .
off - line analyses of recordings were performed , and on average 18 artifact - free edc muscle fibers per patient were selected to assess their mean mcd .
1figures representing a normally ( on the top ) and an abnormally ( on the bottom ) jittered fibers figures representing a normally ( on the top ) and an abnormally ( on the bottom ) jittered fibers movements were recorded at 100  hz in three dimensions ( 3d ) using an infrared optoelectronic - tracking - system ( elite , milan , italy ) with a reflective marker attached to the tip of the index finger and another marker to the movement target .
participants were seated with the target in the medio - sagittal plane on eye level .
they were instructed to start with the right arm extended to the right , to touch the target with high precision ( but fast ) without any trunk movement , to go back to the starting position and to repeat above movements , in a given pace over 15  s ( one trial ) to result in 810 movements ( fig .  2 ) .
the used cartesian coordinate system is head - fixed with a nasooccipital , a horizontal and a vertical axis and the origin in the target . since in our previous study   abnormalities in migraineurs were most pronounced in the horizontal plane , we limited ourselves to an analysis of the mean deviation in the horizontal plane ( in millimeters ) , measured over four trials , each consisting of 810 arm movements . 

2experimental setup for the movement task experimental setup for the movement task quantitative variables in each group of migraine patients ( mo and mta ) were expressed as medians .
the spearman rank order correlation test was used to compare the values of the mean mcd on sfemg and the mean horizontal deviation on 3d - movement analysis .
thirteen migraine patients ( ichd - ii )   were recruited from the headache clinic of the headache research unit in lige , belgium .
eight patients suffering from typical aura with migraine headache ( mta  ichd - ii code 1.2.1 ; three women and five men ; median age 28.5  years ; range 1367 ) and five patients with migraine without aura ( mo  ichd - ii code 1.1 ; three women and two men ; median age 40.0  years ; range 3151 ) underwent both stimulation - sfemg and 3d - movement analysis .
none of them had any other medical condition detectable by history and clinical examination ; none was taking drugs on a regular basis , nor had taken any drug within 3  days before the recordings .
the recordings took place at least 3  days after and before an attack ( checked by telephone - interview ) .
the study was conducted after approval of our institution s ethics committee and performed in accordance with the ethical standards of the 1964 declaration of helsinki , with the understanding and consent of each involved subject .
a nicolet viking iv device ( nicolet biomedical , madison , wisconsin , usa ) was used for stimulation single fiber electromyography .
single muscle fiber activity was recorded with 25-mm - long single fiber needles ( medelec neurodiagnostic accessories , ref : 16829 , witney , oxfordshire , uk ) , and the motor nerve was stimulated with nicolet teflon - insulated monopolar needles .
we stimulated suprathreshold the motor branch of the radial nerve and assessed the variability in latency , i.e. the jitter ( fig .  1 ) , of single fiber action potentials in m. extensor digitorum communis ( edc ) of the right arm . stimulations 
off - line analyses of recordings were performed , and on average 18 artifact - free edc muscle fibers per patient were selected to assess their mean mcd .
mean value of consecutive differences  ( mcd ) of successive interpotential intervals , as usual in sfemg studies . 

1figures representing a normally ( on the top ) and an abnormally ( on the bottom ) jittered fibers figures representing a normally ( on the top ) and an abnormally ( on the bottom ) jittered fibers
movements were recorded at 100  hz in three dimensions ( 3d ) using an infrared optoelectronic - tracking - system ( elite , milan , italy ) with a reflective marker attached to the tip of the index finger and another marker to the movement target .
participants were seated with the target in the medio - sagittal plane on eye level .
they were instructed to start with the right arm extended to the right , to touch the target with high precision ( but fast ) without any trunk movement , to go back to the starting position and to repeat above movements , in a given pace over 15  s ( one trial ) to result in 810 movements ( fig .  2 ) .
the used cartesian coordinate system is head - fixed with a nasooccipital , a horizontal and a vertical axis and the origin in the target . since in our previous study   abnormalities in migraineurs were most pronounced in the horizontal plane , we limited ourselves to an analysis of the mean deviation in the horizontal plane ( in millimeters ) , measured over four trials , each consisting of 810 arm movements . 

2experimental setup for the movement task experimental setup for the movement task quantitative variables in each group of migraine patients ( mo and mta ) were expressed as medians .
the spearman rank order correlation test was used to compare the values of the mean mcd on sfemg and the mean horizontal deviation on 3d - movement analysis .
on sfemg , the median value for mean mcd was not significantly different between mo ( 16.05  s ; range 9.5022.93 ) and mta ( 18.91  s ; range 11.5024.55 ) .
the median value of mean horizontal deviation was 4.01  mm ( range 3.25 to 18.12 ) in mo and 10.74  mm ( range 1.6017.03 ) in mta , a nonsignificant difference . in mo
by contrast , in mta , both variables were positively correlated ( r  =  0.71 , p  =  0.046 ) ( fig .  3 ) . 

3scatter plot relating mean mcd on sfemg ( x axis , s ) and mean horizontal deviation on 3d analysis of a reaching arm movement ( y axis , mm ) , and linear regression lines .
migraine without aura patients ( mo ) : squares , dashed line . migraine with aura patients ( mta ) : triangles , continuous line   scatter plot relating mean mcd on sfemg ( x axis , s ) and mean horizontal deviation on 3d analysis of a reaching arm movement ( y axis , mm ) , and linear regression lines .
our within - patient analysis shows that , in migraine with aura , the mean mcd on sfemg increases significantly with the degree of horizontal deviation in a visually guided reaching movement .
this suggests that , in subgroups of migraine patients , neuromuscular transmission ( nmt ) performance and control of ballistic movements by the lateral cerebellum are similarly influenced by a common biochemical and/or neural mechanism .
although no gene mutations have been identified till now , the genetic load is thought to be higher in the pathogenesis of migraine with aura than that without aura . in familial hemiplegic migraine 1 ( fhm1 ) ,
mutations have been found in the cacna1a gene , which codifies for the main subunit of p / q - type ca channels , heavily concentrated at the neuromuscular junction and in the cerebellum [ 1518 ] .
thus , we initially hypothesized that the nmj and cerebellar abnormalities found in some migraine patients might be due to dysfunctioning ca channels . however , sfemg studies were normal in fhm1 , and mutations in the cacna1a gene are not found in patients suffering from the common forms of migraine , with or without aura . some evidence that the cacna1a gene may be involved in migraine with typical aura , and the facts that nmt impairment can be found in episodic ataxia type 2 , an allelic disorder of fhm1 , and normalizes after treatment with acetazolamide   are still in favor of a possible involvement of cachannels , particularly in migraine with aura .
other proteins implicated in migraine pathophysiology may constitute a common link between neuromuscular junctions ( nmj ) and the cerebellum .
this is unlikely for the alpha-2 subunit of the na - k atpase , of which the gene atp1a2 is mutated in fhm2 , because the alpha-2 isoform is found at intracellular membranes   and not at the nmj , where the major role is played by the alpha-3 isoform .
by contrast , a different group of calcium channels , the r - type , influence neuromuscular transmission and can compensate for dysfunctioning p / q channels .
moreover , they seem to play a role in cerebellar functions ; thus , their activity may influence in parallel nmj and cerebellar performances , similarly to what we found in the subgroup of migraineurs with aura .
the cacna1e gene , which codes for the alpha-1e subunit of r - type channels , is precisely located on locus 1q31 , for which significant linkage was found in the common forms of migraine , and a single nucleotide polymorphism was more frequent in subgroups of patients affected by migraine with aura . in conclusion , the correlation between nmj and cerebellar performances that we have found in migraine with aura patients might be due to a common genetically determined molecular mechanism , possibly influencing ion channels functions , but this has still to be proven by appropriate genetic studies .
 in previous studies , we described subclinical abnormalities of neuromuscular transmission and cerebellar functions in migraineurs . 
 the aim of this study was to search if these two functions are correlated in the same patient . 
 thirteen migraineurs [ five without aura ( mo ) and eight with aura ( ma ) ] underwent both stimulation - sfemg and 3d - movement analysis . single fiber emg ( sfemg ) results were expressed as the  mean value of consecutive differences  
 ( mean mcd ) . 
 precision of arm - reaching movements ( measured with an infrared optoelectronic tracking system ) was expressed as the average deviation in the horizontal plane . 
 median values of mean mcd and mean horizontal deviation were not different between mo and ma . 
 however , in ma , but not in mo , both variables were positively correlated . 
 thus , we conclude that neuromuscular transmission and cerebellar functions are correlated in the same patient when affected by migraine with aura . 
 we suggest that this correlation might be due to a common molecular abnormality . 
Introduction
Materials and methods
Patients
SFEMG recordings
3D-movement analysis
Results
Discussion