Neuroradiology and headaches

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1 J Hedche Pin (2006) 7: DOI /s TUTORIAL Andre Romno Vlentin Ciprini Alessndro Bozzo Neurordiology nd hedches Received: 25 Octoer 2006 Accepted in revised form: 6 Novemer 2006 Pulished online: 10 Decemer 2006 A. Romno ( ) V. Ciprini A. Bozzo Deprtment of Neurordiology, L Spienz University of Rome Snt Andre Hospitl Vi di Grottross 1035 I Rome, Itly E-mil: ndre.romno@unirom1.it Astrct Hedche is one of the most common outptient pin conditions encountered in oth physicin offices nd emergency deprtments. Estlishment of n ccurte dignosis, ccomplished only y thorough history followed y physicl exmintion, is criticl efore tretment cn e initited. Mny ptients undergo evlution with computed tomogrphy nd more recently mgnetic resonnce imging to exclude importnt normlities. It is known tht little percentge of ptients showed significnt neurordiologicl normlities nd the rte of significnt intrcrnil normlities in ptients with hedche nd norml neurologicl exmintion exists. Keywords Hedche Mgnetic resonnce Computed tomogrphy Introduction Hedches with ttendnt pin nd deilittion hve een noted throughout recorded medicl history. New gret scientific results hve een otined since the etiologic theories included curses of the gods, evil spirits, imlnce of humours nd mny other eqully imgintive ides. Tody, fortuntely, some things hve chnged [1]. Hedche is one of the most common outptient pin conditions encountered in oth physicins offices nd emergency deprtments. Estlishment of n ccurte dignosis, ccomplished only y thorough history followed y physicl exmintion, is criticl efore tretment cn e initited. Although the mjority of ptients who present with chronic or recurrent hedche do not hve neurologicl normlities, mny ptients undergo evlution with computed tomogrphy (CT) nd more recently mgnetic resonnce imging (MRI) to exclude eventul diseses responsile for the symptoms. MRI is more sensitive thn CT in the detection of lmost ll intrcrnil normlities. Despite this, limited dt exist out the utility of hed MRI in ptients with hedche. In recent pper from Sempere et l. [2], which considered 1876 ptients with hedche (ny type strted 4 weeks efore neuroimging), 1.2% of ptients showed significnt neurordiologicl normlities nd the rte of significnt intrcrnil normlities in ptients with hedche nd norml neurologicl exmintion ws 0.9%. The uthors

2 423 concluded tht the proportion of ptients with hedche nd intrcrnil lesions is reltively smll, ut neither neurologicl exmintion nor the fetures in the clinicl history permit us to rule out such normlities. There is generl greement tht imging should e performed in cse of importnt chnges in the type of hedche, in cse of first or worst episode, when the onset is sudden or provokes wkening during sleeping, when neurologicl symptoms re ssocited, in very young or old people (over 5 nd 50 yers), in ptients with cncer nd pregnncy, when there re consciousness chnges nd when hedche is relted to Vlslv mnoeuvres or sexul ctivity. In the first prt we will discuss the min neurordiologicl findings tht cn e evluted in primry nd secondry hedches y conventionl imging. In the second prt of this tutoril we will report the more recent results in the pplictions of functionl imging in the study of pthophysiology of primry hedche. Conventionl imging in primry hedches Migrine Migrine is thought to e progressive inflmmtory neurovsculr disorder ssocited with considerle disility nd impirment of qulity of life. It is disese ccompnied not only y chrcteristic throing pin, ut lso y ssocited symptoms nd disility. Migrine hedche frequently is preceded y prodrome, known s ur. The ur in migrine is clerly defined neurologic deficit, most often visul in nture, such s scotoms or visul field chnges [1]. The role of imging nd specificlly of conventionl MRI is still deted. The ssocition of migrine phenomen with neuroimging normlities, s demonstrted y CT nd MRI, hs een the suject of much dete [3]. In study y Ziegler et l. [4], 18 cses of migrine with ur were considered. Only in four of the migrine ptients were res of incresed signl intensity in T2- weighted imges identified. In three of the norml controls similr res were seen s well. The uthors concluded tht these smll res, difficult to identify, my e of multiple etiologies. Similr smll unidentified right res hve een seen not uncommonly in the symptomtic older popultion. In nother study, y Igrshi et l. [5], the uthors ssumed tht repetition of migrine, with repeted episodes of cererl hypoperfusion responsile for ur, could cuse permnent ischemic chnges in the rin. The chrcteristics of MRI lesions in migrine were well defined smll foci on T2-weighted nd proton densityweighted imges in the white mtter. These white mtter lesions resemle so-clled unidentified right ojects (UBOs) [6], which re often relted to geing, hypertension nd other therosclerotic risk fctors. In this study 39.6% of ptients with migrine showed smll white mtter lesions on MRI. The incidence of white mtter lesions ws not different etween ptients with nd without ur. No significnt links with risk fctors were found. A group of ptients with migrine under 40 yers old without risk fctors showed significntly higher incidence of positive MRI chnges (29.4%) thn the controls (11.2%). The side of the MRI lesions did not lwys correspond to the side of usul ur or hedche. The migrine my e ssocited with erly pthologic chnges in the rin. MRI studies in ptients with migrine showed focl res of high intensity on oth T2-weighted nd proton density-weighted MR imges distriuted ilterlly in the white mtter of the rin [5]. These results re similr to those report y Soges et l. [7], who studied 24 ptients with migrine nd found 46% of them showed norml MRI studies. Their slightly higher percentge for positive MRI might e explined y the slightly older men ge (36.8 yers) thn Igrshi et l. s ptients (34.0 yers). The most tempting specultion to explin rin lesions in migrine is tht repeted ttcks of hypoperfusion during ur might cuse permnent ischemic chnges [5] nd frequency of ttcks is n importnt indictor of existence of white mtter foci [8]. Ischemi or n immune-sed white mtter demyelinistion re other possile mechnisms for the white mtter lesions [9]. Such high incidence of hyperintense foci in the white mtter of ptients with migrine ws not confirmed y other studies. Osorn et l. demonstrted prenchyml rin lesions in only 12% of ptients with migrine with ur [10]. In recent study pulished in JAMA in 2004, no significnt differences etween ptients with migrine nd controls in overll infrct prevlence were found. However, in the cereellr region, ptients with migrine hd higher prevlence of infrct thn controls. Among women, the risk for higher white mtter lesion lod ws incresed in ptients with migrine compred with controls. This risk incresed with ttck frequency [11]. The sme uthors more recently underlined tht rin infrction occurs fr more frequently thn expected in migrine ptients, eing most pronounced in migrine with ur (8% hve suclinicl cereellr infrcts). Most infrcts remin cliniclly silent. Femle migrine ptients re t incresed risk of deep white mtter lesions, independent of the effects of crdiovsculr risk fctors. The

3 424 influence of migrine severity (ttck frequency) on the risk of oth types of lesions suggests cusl reltionship etween migrine severity nd lesion lod [12]. In recent met-nlysis from Swrtz nd Kern, the uthors demonstrte tht sujects with migrine re t higher risk of hving white mtter normlities on MRI thn those without migrine. This incresed risk is present even in younger individuls who do not hve co-occurring cererovsculr disese risk fctors [13]. Tension-type hedche Benedittis et l. showed tht in the MRI of ptients with tension-type hedche there is higher incidence of white mtter normlities compred to control sujects (33.3% vs. 7.4%). These lesions re distriuted predominntly in the frontl region nd were shown to hve similr incidence compred with ptients with migrine with ur (32.1%) [14]. Cluster hedche (CH) No specific normlities hve een descried in cluster hedche in conventionl MRI. When n cute CH ttck ws triggered with nitroglycerin (NTG), vsodilttion ws oserved with PET occurring in the ipsilterl posterior inferior hypothlmic grey mtter, in the contrlterl ventroposterior thlmus, in the nterior cingulte cortex, in the ipsilterl sl gngli, in the right nterior frontl loe nd in oth insule. In ptients out of the group who experienced only mild NTG hedche, ctivtion ws seen ilterlly in the insule nd frontl cortices, the nterior cingulted cortex, the right thlmus nd the left sl gngli, ut not in the hypothlmic grey re. In ddition, the uthors found significnt ctivtion (vsodilttion) in the region of the mjor sl rteries, which ws cused in prt y NTG ut ws lso oserved in the spontneous cse nd could e induced y cpsicin injection into the forehed [15]. Conventionl imging in secondry hedches Hedches re one of the most common symptoms tht neurologists evlute. Although most re cused y primry disorders, the list of differentil dignoses is one of the longest in ll of medicine, with over 300 different types nd cuses [16]. Fig. 1 Sudurl hemtom on CT () nd MRI () imges. In these cses CT nd, even etter, MRI cn show the hemtom nd the rin compression Hedche ttriuted to hed nd/or neck trum The min pthologies responsile for this type of hedche re represented y trumtic intrcrnil hemtom, epidurl or sudurl hemtom nd lso y post-trumtic cute or chronic hed injury. Crniotomy might e responsile for this form of hedche s well. Sudurl hemtom (Fig. 1) must e considered, especilly in elderly people, ecuse the trumtic event cn e unremrkle nd no specific neurologicl symptoms might e ssocited. In these cses CT nd, even etter, MRI cn show the hemtom nd the eventul rin compression leding to possile surgicl procedures [17]. Hedche ttriuted to crnil or cervicl vsculr disorders The pthologies responsile for this type of hedche re trnsient ischemic ttcks (TIA), ischemic stroke, intrcrnil or surchnoid hemorrhge (SAH), scculr neurysm, rterio-venous mlformtion (AVM), rteritis (Gignt cell rteritis), crotid rtery dissection, cererl venous thromosis nd pituitry hemorrhge. SAH (Fig. 2) must e considered when new episode of hedche is present ssocited to nuchl rigidity. In the cute phse of SAH, CT is the study of choice, eing le to show even smll mount of lood in the surchnoid spces. If SAH is demonstrted y CT scn, spirl CT ngiogrphy cn identify the presence of the neurysm responsile for SAH, thus indicting need for further tretment (surgicl or endovsculr). If the clinicl episode is fr from the rdiologicl evlution, MRI might e more sensitive in detecting surchnoid lood when FLAIR sequences re used. These sequences typiclly show the lood with high signl intensity compred to the norml cererospinl fluid.

4 425 Unruptured vsculr mlformtions cn e responsile for prolonged hedche. Artero-venous nd durl mlformtions cuse chnges in rin vsculr hemodynmics. MRA nd CTA cn esily show unruptured vsculr mlformtions ut conventionl ngiogrphy is still mndtory to understnd the exct structure of the normlity. Also the presence of rteriovenous (AV) shunts, such s ptent formen ovle (PFO), cn represent trigger for migrine with ur ttcks. A higher prevlence of PFO ws demonstrted in migrineurs vs. the norml popultion [18]. Venous thromosis (Fig. 3) should e considered when deling with young women using hormone therpy [19]. Venous thromosis cn e identified y mens of MRI nd MRA or y CT ngiogrphy. Prenchyml lesions (frequently hemorrhgic) cn e ssocited s well. Crotidyni is syndrome encompssing mny vrieties of pin in the crotid region. It cn e due to crotid dissection (Fig. 4). In cse of suspect crotid dissection, high signl on T1W cn e demonstrted in the wll of distl internl crotid rtery. The hemtom might produce reduction of the lumen size t MRA. Neurologicl symptoms (either centrl deficit or hypoglossl nerve compression) cn e ssocited [17]. Migrine my represent predisposing condition for spontneous cervicl rtery dissection [20]. Pituitry hemorrhge cn cuse sudden nd strong hedche. This my e relted to previous therpy for pituitry denom or not. MRI cn esily show the lood inside the glnd nd follow-up cn document prtil or complete resolution of the disese (Fig. 5). Close follow-up must e considered to rule out dngerous optic nerve compression. c d Fig. 2 Surchnoid hemorrhge (SAH). In () nd () SAH in the cute phse is evident on the CT study. CT ngiogrphy study (c) demonstrtes the presence of the neurysm responsile for SAH in the M2 segment of middle cererl rtery (rrow). FLAIR sequence might e more sensitive thn CT in detecting surchnoid lood in the first dys fter the cute event. The lood is shown s high signl intensity ltertion compred to the norml cererospinl fluid (d, rrow) Fig. 4 Crotid dissection. High signl on T1-weighted imge is oserved in the wll of left distl internl crotid rtery (, rrow). The hemtom produces reduction of the lumen size t MRA (, rrow) Fig. 3 Right trnsverse nd sigmoid sinuses thromosis. The T1 hyperintensity inside the sinuses () nd the occlusion of them in the MR ngiogrphy study re evident (). The high signl in MIP reconstruction of MRA is due to the intrinsic hyperintensity of the clot visile on conventionl xil T1-weighted imges (rrows) Fig. 5 Pituitry hemorrhge oserved s hyperintense re inside the glnd in the cute phse () nd s n re of reduced vsculristion post-contrst () in the follow-up

5 426 Hedche ttriuted to non-vsculr intrcrnil disorder There re mny non-vsculr intrcrnil disorders responsile for hedche-like idiopthic intrcrnil hypertension, high or low cererospinl fluid pressure, septic meningitis, intrcrnil neoplsm, epilepsy, hypothlmic or pituitry hyper- or hyposecretion. Only minority of ptients who hve hedches hve rin tumours. Some loctions re more likely to produce hedche (e.g., posterior foss tumour cuses hedche more often thn suprtentoril tumour) [21]. All slow-growing intrcrnil neoplsm, typiclly low-grde glioms, ut lso enign rchnoid cysts, my led to hedche without specific neurologic symptoms (Figs. 6, 7). All the pthologies le to cuse chnges in Fig. 6 Low-grde gliom of the right temporl loe s seen in these T2-weighted MRI (FLAIR sequences) (,, rrows) the cererospinl fluid circultion leding to hydrocephlus should e considered s well (Fig. 7). In study y Boirdi et l. [22], the uthor showed tht hedche hiding rin tumour is rther similr to tension hedche in 77% of cses. In 5% 10% of cses it could mimic clssic migrine; otherwise it presents s mixed form with tension nd clssic migrine comintion. Some studies investigted the indictions of neuroimging studies in the evlution of different types of primry hedches [23]. In prticulr, in study y Wng et l. [24], more thn 400 ptients with chronic hedche were retrospectively reviewed. From these results it emerged tht the typicl hedche type ws the most significnt predictor of orgnic cuses. The typicl findings of idiopthic intrcrnil hypertension (pseudotumour cereri) re represented y smll ventricles, poor visulistion of surchnoid spces nd dilttion of the perioptic nerve sheths. Chronic sinus thromosis must e excluded using MRA with gdolinium-enhnced techniques. Other possile cuses like Chiri I mlformtions (Fig. 7) must e considered nd identified looking t the position of cereellr tonsils on the midline sgittl MRI. In cse of low CSF pressure (Fig. 8), smll sudurl fluid collection hs een descried showing enhncement fter intrvenous injection of gdolinium. These findings cn e pprecited ehind the clivus s well. Idiopthic form should e differentited secondry form, looking for cererospinl fluid lekge in the spinl roots. This is ctully done, in the first step, using myelo-mr exmintion. Hedche ttriuted to infection Bcteril or lymphocytic meningitis, encephlitis, rin scess, sudurl empyem nd systemic infection my c Fig. 7 Possile cuses of derngement of cererospinl fluid circultion. Chiri I mlformtions (), rchnoid cyst () nd colloid cyst (c). In nd c ventriculr dilttion is the cuse of endocrnic hypertension. In the growth of the rchnoid cyst cn led to rin compression Fig. 8 A cse of low CSF pressure with ilterl smll sudurl fluid collection (, rrows) nd durl enhncement fter intrvenous injection of gdolinium ()

6 427 e responsile for hedche. This type of hedche is chrcterised y diffuse or continuous pin ccompnied y nuse nd/or focl neurologicl symptoms nd/or signs. A direct spce-occupying effect leding to rised intrcrnil pressure nd/or irrittion of the meningel or rteril structures re the mechnisms for cusing hedche [17]. MRI with diffusion-weighted imges (DWI) cn e esily chrcterised y the presence of rin scess due to the typicl restriction of diffusion inside the scess cvity. Using these imging chrcteristics we cn esily differentite n scess from the presence of necrosis inside primry (gliolstom) or secondry (metstsis) tumour of the rin. Hedche ttriuted to disorders of homeostsis Trigeminl neurlgi In idiopthic form the typicl clinicl pttern is ssocited with norml neurologicl nd MRI exmintion. The most common cuse of this form is compression of trigeminl nerve root y n errnt loop of lood vessels (Fig. 10). In study y Roert et l. [26], MRI demonstrted tht compression of the fifth crnil nerve t the root entry zone [27 29] y vsculr structure cn e responsile for trigeminl neurlgi. In nother study y Chrles et l. [30], vsculr conflict with trigeminl nerve t the root entry zone ws seen on FISP imges ( type of thin high-resolution imging with high signl inside the vessels) in 10 of 13 (77%) symptomtic nerves nd only in 8 of 113 (7%) symptomtic nerves. MP- RAGE nd FISP imges demonstrted rteril contct eqully well. The superior cereellr rtery is y fr the most common vessel cusing trigeminl compression (80% of cses). In cse of nerve conflict the rtery typi- A lot of disorders of homeostsis cuse hedche, such s hypoxi, hypercpni, rteril hypertension, hypothyroidism, hypertensive encephlopthy, pre-eclmpsi nd eclmpsi, nemi, drenocorticl insufficiency, hyperldosteronism, polycythemi, Cushing s disese etc. [17]. In eclmpsi MRI cn demonstrte typicl reversile signl ltertions in the prieto-occipitl regions. Hedche or fcil pin ttriuted to disorders of crnium, neck, eyes, ers, nose, sinuses, teeth, mouth or other fcil or crnil structures Fig. 9. Srcom of C2 in ptient with persistent pin in t the se of the skull. () 3D reconstruction nd () xil CT scn (rrow) Pin in the oro-fcil region cn e very distressing for the ptient, s it usully ffects importnt dily living functions, such s chewing, swllowing, tlking nd lughing. Temporo-mndiulr disorders constitute the second most common cuse of oro-fcil pin, following dentl pin. Clinicl exmintion of the oro-fcil pin ptient includes ssessment of crnil nerve function, cervicl spine evlution, plption of mstictory nd neck muscles, temporo-mndiulr joint exmintion nd complete intr-orl nd dentl evlution. Cervicogenic hedche In 16% of cses the lterl tlnto-xil joint is responsile for hedches. Tumour of the sme region my led to cervicogenic pin s well (Fig. 9). There is no clinicl correltion etween chnges seen MRI nd common normlities such s disc degenertion, disc ulges, rthritis nd potentil sources of ptient s pin [25]. c Fig. 10 Neurovsculr conflict. An errnt loop of superior cereellr rtery is the most common vessel cusing trigeminl compression on its root entry zone (,, rrows). It is possile to see hyperintensity on T2-weighted imges in the intrpontine segment of the trigeminl nerve (c, rrow)

7 428 clly runs medilly to the min trigeminl root. A T2 signl ltertion cn e eventully present in the intr-pontine segment of the nerve (Fig. 10). In 15% of ptients with trigeminl neurlgi the cuse of the disorder is represented y multiple sclerosis (Fig. 11) (especilly in young ptients nd when pin is ilterl), with prevlence of 2%. Rrely, other structurl lesions, minly loclised in the pontine region, cn led to trigeminl neurlgi. These include vestiulr or rrely trigeminl schwnnom, meningioms, epidermoid or other cysts (Fig. 12). Vsculr rinstem lesions, especilly pontine infrctions, ngioms or rtero-venous mlformtions, re further cuses of symptomtic trigeminl neurlgi [31]. Pin round the eye This is ssocited with distured vision nd cn e presenting complint for severl oculr disorders. The common neurologicl disorders tht cuse pin round the eye re optic neuritis, inflmmtory or infectious diseses, temporl rteritis nd skull se frctures with lesions of oculr motor nerves. In cse of optic neuritis MRI cn show T2 signl hyperintensity in the ffected, often oedemtous nerve, with incresed gdolinium uptke in the cute phse of the disese [31]. Temporo-mndiulr disorders (TMD) The term refers to vriety of pthologic conditions tht ffect the mstictory musculture, the temporo-mndiulr joints or oth. TMD re clssified into 3 min ctegories: mstictory muscle disorders, rticulr disc derngements nd temporo-mndiulr joint disorders. MRI cn e used to sustntite the clinicl dignosis concerning rticulr disc displcement. Articulr disc derngements re usully chrcterised y displcement of the rticulr disc nteriorly nd medilly. Disc displcement with reduction (Fig. 13) is chrcterised y improvement of the position of the displced disc during opening. An opening nd closing joint clicking cn e herd ut pin my or my not e present. Disc displcement without reduction refers to n ltered disc-condyle structurl reltion tht is not improved during mouth opening. Fig. 12 Epidermoid lesion () nd trigeminl schwnnom (, rrow) leding to trigeminl neurlgi Fig. 11 Young ptient ffected y multiple sclerosis with trigeminl neurlgi. An ctive plque close to the intrpontine segment of the trigeminl nerve is evident in this MRI FLAIR imge (rrow) Fig. 13 Temporo-mndiulr disorder. Articulr disc displcement nteriorly (). Reduction is chrcterised y improvement of the position of the displced disc during opening (). An opening nd closing joint clicking cn e herd ut pin my or my not e present

8 429 understnd the functionl imging possiilities in hedches, it is necessry to rememer how pin structures prticipte in pinful conditions other thn hedche. In migrine with ur the primry event occurs in the cortex nd, including hypothlmus nd thlmus, it finishes in the cortex, mnifesting pin. In migrine without ur, rinstem findings suggest dysfunctionl pin system [36]. Pin is typiclly present in the cute condition, while chronic disc disloction my e non-pinful [32, 33]. Rhinosinus-relted hedche Sinusitis is overdignosed s cuse of hedche ecuse of the elief tht pin over the sinuses must e relted to the sinuses. In fct, frontl hed pin more often is cused y migrine nd tension-type hedche [34]. The est dignostic yield is otined with CT. Axil nd coronl reconstruction from volumetric dt cn esily show the presence of sinus disese (Fig. 14), while MRI is mndtory in ptients with signs of intrcrnil complictions. Stndrd rdiogrphs re flse negtive in out qurter of ptients nd should e voided [31]. Idiopthic (Bell s plsy) This is common disorder nd is often ssocited with fcil pin loclised round the er, jw ngle nd neck. Symptomtic fcil plsy due to different underlying conditions, most often inflmmtory, infectious, compressive, infiltrtive diseses or protid tumours or lesions in the cereellopontine ngle like coustic neurinom, meningiom, cystic lesions or neurysms, tend to e ssocited with hypocusi, vertigo or fcil plsy [31]. Functionl neuroimging of primry hedches Introduction Fig. 14 () CT scn (coronl view) of lrge mucocele of the mxillry sinus; () CT scn with contrst injection (xil view) of ptient with crcinom of the prnsl sinuses The dignosis of the vrious hedche disorders is sed on clinicl fetures s descried y the Interntionl Hedche Society criteri. Neuroimging of hedche ptients hs drmticlly chnged our understnding of the pthophysiology of primry hedches nd provided unique insight into these syndromes [35]. Functionl neuroimging of ptients with hedche is useful to study the pthophysiology rther thn for dignostic purposes. To Migrine with ur Migrine represents the clssic primry hedche nd it is considered to hve primrily vsculr pthogenesis. The pthophysiologicl concept of vsculr hedches, however, is sed on chnges in vessel dimeter or in cererl lood flow. These mechnisms would trigger pin. Regionl cererl lood flow (rcbf) studies hve emphsised dysfunction of the cererovsculr regultion in hedche. Chnges in rcbf, shown y positron emission tomogrphy (PET) studies, reflect vritions in vessel dimeter nd synptic ctivity (inhiition nd excittion). Experimentlly inducing crnil pin, ctivtion (i.e., increse in rcbf, ilterlly) in the nterior cingulte cortex, oth insule, the contrlterl thlmus nd the cereellum re evident [37]. Before these technologicl dvnces, knowledge of the pthogenesis of migrine ws sed lrgely on clinicl oservtions. Hrold G. Wolff [38] proposed tht the neurologicl symptoms of the migrine ur were cused y cererl vsoconstriction nd the hedche y vsodilttion. Lshley [39] ssessed tht corticl spreding depression (CSD) of Leo ws the primry cuse, introducing the concept of the neurl theory of migrine [40]. The slow progression of the visul nd sensory migrine symptoms re chrcteristic of the electrophysiologicl series of events known s CSD. CSD is wve of electricl ctivity followed y neuronl depression, spreding cross the cortex t pproximtely 3 6 mm/min [41]. Numerous studies hve confirmed tht the ur phse of migrine is ssocited with reduction in cererl lood flow [42]. This flow chnge moves cross the cortex s spreding oligemi t 2 3 mm/min [37]. Snchez del Rio et l. reported the results of perfusion weighted imges studies in totl of 28 spontneous episodes of migrine. The uthors oserved decreses in rcbf nd rcbv nd increses in men trnsit time (Fig. 15) in the visul cortex contrlterl to the ffected visul field during 7 episodes of visul ur nd 7 episodes of hedche fter resolution of the ur. No significnt perfusion ws evident in other rin regions. Blood flow chnges oserved during migrine visul ur do not go over the threshold ssocited with ischemic injury, justifying the sence of lesions in diffusion imges [43].

9 430 Fig. 15. Increses in MTT perfusion MRI mp () in the visul cortex contrlterl to the ffected visul field during n episode of visul ur. Other rin regions do not show ny perfusion chnges during the ur or during hedche. Blood flow chnges oserved remin ove the threshold ssocited with ischemic injury, justifying the sence of lesions in diffusion-weighted imges () Cererl perfusion chnges during migrine with ur hve een descried lso y BOLD functionl MRI studies. In the typicl visul ur of migrine, functionl MRI hs reveled multiple neurovsculr events in the occipitl cortex, resuming the CSD: (1) n initil hyperemi lsting min, spreding t rte of 3.5 mm per min, (2) followed y mild hypoperfusion lsting 1 2 h, (3) n ttenuted response to visul ctivtion nd (4) like CSD, in migrine ur, the first ffected re is the first to recover [43]. In recent cse report [44] reversile chnges locted in the right prieto-occipitl cortex on DWI imges were descried in ptient with cute onset of hedche. The presence of positive DWI imges, with the sence of low pprent diffusion coefficient vlue, referred to vsogenic oedem, could e in ccordnce with focl prolonged hyperperfusion ssocited with vsogenic lekge. The correltion nd complete resolution of oth clinicl nd neuroimging normlities could vlidte reversile neuronl inflmmtory pthology in migrine with typicl ur. Another similr finding hs een descried y Jco et l., in which the uthor reported the cse of young womn ffected y spordic hemiplegic migrine (SHM) with reversile chnges on MRI. In this cse, oth DWI nd ADC mps were positive for restricted diffusion of wter; perfusion mps showed incresed vsculrity nd fter gdolinium, n enhncement of grey mtter in the ffected regions ws evident. Spectroscopy study showed reduced NAA/Cr. To explin these results, in the sence of vsculr occlusion, the uthors suggested metolic ltertion t cellulr level with spreding corticl depression leding to dmge of the ATPse pump with ltered memrne permeility [45]. In the lst few yers, severl studies of mgnetic resonnce spectroscopy, non-invsive technique tht llows the investigtion of vritions in some cererl metolites, nd in prticulr 31 phosphorus, demonstrted metolic disturnce in the rin of migrine ptients with ur nd, to lesser extent, of migrine ptients without ur, which is evident even in the interictl period. Such ltertions concern energy metolism nd consist of incresed inorgnic phosphorus nd ADP, reduced phosphocretine nd decresed phosphoryltion potentil. A mitochondril dysfunction ws hypothesised to e the iochemicl sustrte tht could contriute to rin corticl hyperexcitility [46]. In recent 1 H-MRS study, focused on visul cortex, efore nd fter photic stimultion, consistent decrese in the NAA signl in migrine with ur ptients compred with migrine without ur ptients nd control individuls ws noted [47]. In migrine with visul ur ptients ssocited with presthesi, presis or dysphsi (Mplus), lctte incresed only during stimultion, only in visul cortex; in migrine with ur ptients, resting lctte ws high in visul cortex, without further increse during stimultion [48]. In the interictl period Wtne et l. found high lctte levels, speculting tht neroic glycolysis occurs in ptients with migrine [49]. Migrine without ur Frierg nd collegues [41] demonstrted with SPECT tht interictlly lmost 50% of migrine without ur sufferers hd norml interhemisphericl symmetries in rcbf. These symmetries were discrete compred to those seen during the ur phse of migrine ttck. In study of the sme group [50], middle cererl rtery (MCA) velocity studied y trnscrnil Doppler sonogrphy on the hedche side ws significntly lower thn tht on the non-hedche side. The uthors concluded tht in the hedche phse there might e dilttion in the MCA on the hedche side [37]. Cluster hedche Using PET, possile site of the centrl origin of cluster hedche hs een visulised in the hypothlmic grey mtter [51]. During n cute ttck, ctivtion occurs in frontl res, oth insule, contrlterl thlmus nd cingulte cortex. A specific ctivtion ws demonstrted in the ipsilterl hypothlmus. This region is specific for cluster hedche, s it hs not een seen in migrine [37]. Structurl imging with voxel-sed morphometry hs identified n re in the posterior hypothlmic grey s key in understnding cluster hedche. This re is sutly enlrged in its grey mtter volume, ctive during n cute cluster hedche [52].

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