Research in Vestibular Science Vol. 11, No. 2, June 2012 Review pissn 2092-8882, eissn 2093-5501 편두통성현훈의진단과감별진단 충남대학교의과대학신경과학교실 정성해 Diagnosis and Differential Diagnosis of Migrainous Vertigo Seong-Hae Jeong, MD Department of Neurology, Chungnam National University Medical School, Daejeon, Korea Received May 8, 2012 R evised May 12, 2012 Accepted May 12, 2012 Corresponding Author: Seong-Hae Jeong, MD Department of Neurology, Chungnam National University Medical School, 33 Munhwa-ro, Jung-gu, Daejeon 301-721, Korea Tel: +82-42-280-8057 Fax: +82-42-252-8654 E-mail: mseaj@hanmail.net Copyright c 2012 by The Korean Balance Society. All rights reserved. Migrainous vertigo is one of common recurrent vestibular disorders. Because the diagnostic criteria have not been yet settled internationally, we have a difficulty in both diagnosis and research in migraineurs with vertigo. Literature about the diagnostic criteria of migrainous vertigo and its differential diagnosis were reviewed. Until now, the criteria proposed by Neuhauser et al. is regarded as most adequate in diagnosis of migrainous vertigo. Differential diagnosis of migrainous vertigo should be guided by distinction of vestibular symptoms and nonvestibular dizziness and consider the common causes of recurrent vertigo. Just like migraine itself, migrainous vertigo is diagnosed on the basis of history and exclusion of other vestibular disorders mimicking migrainous vertigo. Therefore, delicate history taking is the most important in diagnosis and management of patients with migrainous vertigo. Research in Vestibular Science 2012;11(2):45-50 Key Words: Migraine; Vertigo; Diagnosis 서론편두통성현훈 (migrainous vertigo) 은청력증상없이나타나는재발성어지럼의대표적인원인중하나이다. 그러나, 확진을위한생물학적표지자 (biological marker) 나검사법이없고, 진단의과정이병력에의존하고, 다른질환들을배제하여이루어지므로, 임상진료와연구에있어어려움이있다. 1 기존연구에서편두통과연관된어지럼을시사하는용어들 (migrainous vertigo, 1 vestibular migraine, 2,3 migraine related vestibulopathy, 4 basilar-type migraine, migraine related vertigo or dizziness, 5 migraine-associated dizziness, benign recurrent vertigo 6 ) 이다양한것또한이를반영한다고할수있다. 최근에는 migrainous vertigo라는용어보다 vestibular migraine이더적합하다고주장하는그룹도있다. 그이유는 migrainous vertigo에비해 vestibular migraine은편두통환자에서보이는전정및비전정증상을모두포함하여, 더적합하다는설명이다. 3 본고에서는편두통환자에서수반되는어지럼중전정증상을강조한, 편두통성현훈 이라는용어를이용하여다른전정질환과구분되는면을강조하고자한다. 임상적으로편두통성현훈은양성돌발성두위현훈, 심인성어지럼과함께재발하는어지럼의대표적인원인을차지하며, 편두통치료에의해호전되는경향을보여, 이에대한적절한인식은연구뿐만아니라임상에서적절한진료를위해필요하다고본다. 편두통이란? 편두통은반복적으로박동성의일차성두통이오심, 구토, 빛혐오증, 소리혐오증등을수반하는경우진단할수있 45
Res Vestibul Sci Vol. 11, No. 2, Jun. 2012 Table 1. Diagnostic criteria for migraine without aura (International Headache Society, 2004) 7 A. At least five attacks fulfilling criteria B-D B. Headache attacks lasting 4-72 hours C. Headache has at least two of the following characteristics: 1. Unilateral location 2. Pulsating quality 3. Moderate or severe pain intensity 4. Aggravation by routine physical activities (e.g., walking or climbing stairs) D. During headache at least one of the following: 1. Nausea or vomiting 2. Photophobia and phonophobia E. Not attributed to another disorder Table 2. Diagnostic criteria for migraine with aura (International Headache Society, 2004) 7 A. At least 2 attacks fulfilling criteria B-D B. Aura consisting of at least one of the following but no motor weakness: 1. Fully reversible visual symptoms including positive features (e.g,. flickering lights, spots or lines) and/or negative features (i.e., loss of vision) 2. Fully reversible sensory symptoms including positive features (i.e., pins and needles) and/or negative features (i.e., numbness) 3. Fully reversible dysphasic speech disturbance C. At least two of the following: 1. Homonymous visual symptoms and/or unilateral sensory symptoms 2. At least one aura symptom develops gradually over 5 minutes 3. Each symptom lasts 5 and 60 minutes D. Headache fulfilling criteria B-D for 1.1 Migraine without aura begins during the aura or follows aura within 60 minutes E. Not attributed to another disorder 다. 7 편두통의진단은국제두통학회 (International Headache Society, 2004) 에서제시한기준을따른다 (Tables 1, 2). 7 일반적인편두통의진단기준에포함된증상은아니지만, 일반인에비해편두통환자에서현훈의빈도가유의하게높음은이미잘알려져있다. 8 편두통에대한임상적이해없이편두통과연관된어지럼의진단은어렵다. 따라서, 편두통성현훈의진단을위해서는편두통의진단기준에관한정확한임상적이해가선결되어야한다. 편두통과관련된어지럼의종류 편두통과연관된다양한어지럼질환은다음 7 가지로분 류할수있다. 1 1) 편두통의조짐 (aura) 로나타나는현훈 ( 기저형편두통 ) 7 2) 양성재발성현훈 (benign recurrent vertigo) 이나소아기양성돌발성현훈 (benign paroxysmal positional vertigo of childhood) 같은무두통편두통 (migraine equivalent) 6 3) 편두통에서두통의동반증상으로나타나는현훈 ( 편두통성현훈 ) 1 4) 비두통기의동요병 (motion sickness) 9 5) 가족성편마비편두통 (familial hemiplegic migraine), 삽화실조증 2형 (episodic ataxia type 2), 척수소뇌실조 6형 (spinocerebellar ataxia type 6) 등의유전자변이와관련된어지럼 10 6) 불안장애, 기립성저혈압등의동반이환질환및편두통예방약제과관련된어지럼 11 7) 편두통과통계적으로연관성이제기되고있으나직접적인인과관계가불분명한메니에르병이나양성돌발성두위현훈등의전정질환 12,13 이중편두통성현훈은편두통의병태생리와연관된전정성어지럼에해당한다고할수있다. 1 이는편두통환자에서단순히두통과반복적인현훈이있다하여쉽게편두통성현훈으로진단할수없음을의미한다. 편두통성현훈을기저형편두통진단기준으로진단할수있을까? 국제두통분류상현훈이진단기준에포함된두통에는기저형편두통, 소아기양성돌발현훈두가지가있는데, 성인에서국제두통분류에의거하여, 즉편두통성현훈을기저형편두통으로진단하는경우는매우드물다 (Table 3). 3,7 그이유는다음과같다. 첫째, 기저형편두통에서의현훈은 9가지전조증상중하나이며, 국제두통분류상전조증상은 5분이상에걸쳐서서히진행한후 5분이상한시간미만지속되는신경학적증상으로정의된다. 그러나, 실제로편두통성현훈의경우수초에서수시간이상까지다양한지속시간을보인다. 둘째, 기저형편두통의경우전조증상이사라진후한시간이내에편두통이시작되어야하는것으로규정하고있으나, 편두통성현훈의경우두통과동반되지않는경우가적지않다. 셋째, 기저형편두통의진단기준에부합하기위해서는 46
정성해. 편두통성현훈의진단과감별진단 Table 3. Basilar-type migraine (International Headache Society, 2004) 7 A. At least 2 attacks fulfilling criteria B-D B. Aura consisting of at least two of the following fully reversible symptoms, but no motor weakness: 1. Dysarthria 2. Vertigo 3. Tinnitus 4. Hypacusia 5. Diplopia 6. Visual symptoms simultaneously in both temporal and nasal fields of both eyes 7. Ataxia 8. Decreased level of consciousness 9. Simultaneously bilateral paraesthesias C. At least one of the following: 1. At least one aura symptom develops gradually over 5 minutes and/or different aura symptoms occur in succession over 5 minutes 2. Each aura symptom lasts 5 and 60 minutes D. Headache fulfilling criteria B-D for 1.1 Migraine without aura begins during the aura or follows aura within 60 minutes E. Not attributed to another disorder 현훈이외에시각증상등의한가지이상의다른전조증상이동반되어야하나, 편두통성현훈의경우그렇지않다. 따라서, 편두통성현훈의진단기준으로기저형편두통은부적합하며, 다른기준이필요하다. 편두통성현훈의진단 편두통성현훈에관해과학적으로체계적인보고를시도한것은약 1980년대부터이다. 현재까지진단기준으로가장널리사용되는것은 2001년 Neuhauser 등 1 이제시한것으로다음과같다 (Table 4). 1) 중등도이상의일과성전정증상 ( 회전성 / 체위변환성현훈, 본인이나물체가움직인다고느끼는착각, 두위움직임에의해악화 ) 2) 국제두통학회진단기준에부합하는편두통 3) 적어도두번이상의현훈발작동안다음증상중하나이상동반, 편두통성두통 (migrainous headache), 빛혐오증, 소리혐오증, 시각혹은다른전조증상 4) 적절한검사소견을통해어지럼의다른원인이배제. 위네가지기준을모두만족하는경우명확한편두통성현훈 (definite migrainous vertigo) 으로진단하였다. 또한, 의미있는현훈의정도를중등도이상으로정의하 Table 4. Diagnostic criteria for migrainous vertigo (Neuhauser et al. 2001) 1 Definite migrainous vertigo A. Episodic vestibular symptoms of at least moderate severity B. Current or previous history of migraine according to the criteria of the International Headache Society C. One of the following migrainous symptoms during 2 attacks of vertigo: migrainous headache, photophobia, phonophobia, visual or other auras D. Other causes ruled out by appropriate investigations Comment: Vestibular symptoms are rotational vertigo or another illusory self or object motion. They may be spontaneous or positional. Vestibular symptoms are moderate if they interfere with but do not prohibit daily activities and severe if patients cannot continue daily activities. Probable migrainous vertigo A. Episodic vestibular symptoms of at least moderate severity B. One of the following: a. Current or previous history of migraine according to the 2004 criteria of the International Headache Society b. Migrainous symptoms during vestibular symptoms c. Migraine precipitants of vertigo in more than 50% of attacks: food triggers, sleep irregularities, hormonal change d. Response to migraine medications in more than 50% of attacks C. Other causes ruled out by appropriate investigations 였는데, 중등도 (moderate) 현훈은일상생활을방해할정도이나지속할수있는경우를말하며, 중증 (severe) 은일상생활을영위할수없는정도로심한경우를일컫는다. 즉, 편두통진단기준에서두통의강도와마찬가지로, 편두통성현훈에서의어지럼도일상생활을방해할정도로심한경우에의미있다고보았다. 이는관련현훈의양상과정도를구체적으로기술해, 기립성저혈압과같은비전정성어지럼의경우는제외하고, 전정질환으로서의편두통성현훈을진단하기위함이다. 14 또한, 편두통진단기준과같이소리 / 빛혐오증이나전조증상만을현훈과수반되는의미있는증상으로진단기준에제시하였다. 즉, 오심의경우다른현훈에서도수반될수있는비특이적증상으로여겨제외하였다. 이외에냄새혐오증 (osmophobia), 수면, 호르몬변화, 알코올섭취등의인자에대한영향, 편두통치료에대한반응여부등도편두통진단기준과마찬가지로명확한편두통성현훈진단에는포함하지않았다. 이진단기준을적용한 Neuhauser 등 1 의연구결과대조군의경우 24%, 어지럼클리닉에내원하는환자의 38% 에서편두통을호소하는것으로나타나유의하게어지럼환 47
Res Vestibul Sci Vol. 11, No. 2, Jun. 2012 자에서편두통의유병률이높아편두통과현훈의관련성을다시한번확인할수있었다. 또한어지럼클리닉에내원하는환자의 7%, 편두통클리닉에내원하는환자의 9% 가명확한편두통성현훈의진단기준을모두만족시키는것으로나타났다. 이중약반수 (15/33) 에서는두통과현훈은동반되었고, 나머지반수 (16/33) 에서는동반되기도하고, 동반되지않기도하였으며, 일부소수 (2/33) 에서두통과어지럼은항상따로발생하였다. 그러나, 실제임상에서중등도이상의재발성현훈을호소하는환자중기존의다른질환으로설명되지않으면서, 진단기준을만족하는편두통이없거나, 아예두통없이현훈만을경험하여, 명확한편두통성현훈진단기준을만족하지않으면서도현훈발작이편두통에수반되는증상이나유발인자에의해발생하여여전히편두통성현훈의가능성이있다고생각되는경우가있는데, 이는 Neuhauser 진단기준에따르면가능성이높은편두통성현훈 (probable migrainous vertigo) 에해당한다고할수있다. 진단기준은다음과같다. 1) 중등도이상의일과성전정증상회전성 / 체위변환성현훈, 본인이나물체가움직인다고느끼는착각, 두위움직임에의해심해짐 2) 다음중하나이상을만족하는경우 (1) 국제두통학회기준에부합하는편두통 (2) 현훈발작동안편두통증상이동반 (3) 현훈발작이편두통유발인자 ( 특별한음식, 수면이상, 호르몬변화 ) 와연관됨 (4) 편두통치료약제에대한반응 3) 적절한검사소견을통해어지럼의다른원인이배제물론편두통성현훈의진단을위한생물학적표지자나확진법이없고, 국제기준이아직제시되지않은이시점에서이들진단기준의민감도와특이도를구하기는어렵다. 그러나, 본진단기준중명확한편두통성현훈의기준은특이도를보다높일수있고, 가능성이높은편두통성현훈의진단기준은민감도를높일수있다는점에있어어느정도실제연구와임상적인면에있어유연성을제시할수있다는장점이있다고본다. 또한, Neuhauser 진단기준을적용하여국내편두통환자를대상으로멀미정도와전정안반사를비교한연구결과명확한또는가능성이높은편두통성현훈환자들사이에유의한차이가없었던점또한이두군을동질 (homogenous) 환자군으로보는데, 크게무리가없음을시사한다. 9 감별진단편두통성현훈의감별진단은전정증상과비전정증상의구별, 다른재발성현훈의원인질환을배제하는것이중요하다. 1. 전정메니에르병 (Vestibular Meniere s disease) 과거반복적인현훈증상이없이청각증상만보이는 cochlear 메니에르병과비교하여사용된용어로서메니에르병의발생초기에청각증상없이주기적인현훈만을보이는경우를의미했지만많은질환이청각증상없이반복적인어지럼으로발현할수있기때문에더이상사용되지않는다. 전정성메니에르병으로진단된환자를추적관찰한결과불과 25% 환자에서만청각증상을가지는전형적인메니에르병으로이행하였고반수이상의환자는청력증상없이반복적인현훈만을보였고이들대부분에서편두통이동반되었다는연구결과를볼때많은환자들이실제로는편두통성현훈환자일것으로생각된다. 15 2. 양성재발성현훈 / 재발성전정병증 (Recurrent vestibulopathy) 청각증상, 다른신경학적이상없이반복현훈을보이는환자들의분류에있어이들진단명이사용되어왔으며, 이들중상당수가편두통성현훈환자들일것으로생각된다. 그러나, 실제로이들환자의모든경우가편두통성현훈으로설명되지않는경우도있다. 따라서, 편두통성현훈진단에맞는환자들은편두통성현훈으로진단을명확히하고, 이외의환자들에대한관련기전과치료및예후에대해관심을기울이는것이필요하다고본다. 16,17 3. 소아기양성돌발현훈소아에서반복적인현훈발작이발한및구토를동반하며대개수분후정상으로되돌아와서아무일이없었던것처럼다시놀이에열중한다. 일부소아는빙빙도는어지럼을부모에게표현하지만대부분은자신이경험한이상한증상이빙빙도는어지럼이라는것을잘알지못하고부모에게표현하지못한다. 뇌파검사및뇌자기공명영상소견상모두정상소견을보이며소아기에나타나는간질과의감별을요한다. 대부분은 7-8세이후증상이소실되나일부에서증 48
정성해. 편두통성현훈의진단과감별진단 상이지속되며대부분이전형적인편두통발작을경험하였다. 18 4. 유전성이온채널병증 1) 가족성편마비성편두통 2) 주기성실조-2형 3) 척수소뇌실조-6형 Voltage gated calcium channel gene (CACNA1A) 유전자의돌연변이가그주된병인이나아직까지동일유전자의변이가어떻게서로다른증상 ( 즉가족성편마비성편두통, 주기성실조-2형및척수소뇌실조-6형 ) 을나타내는지에대해서는확실하지않다. 이들질환에서공히보일수있는전정기능검사소견으로서는시추적성안구운동의이상, 반동성안진, 주시유발성안진, 체위성하박안진, 및전정안반사의시선억제실패등이있다. 특징적으로충동성안구운동의속도및전정안반사의이득 (gain) 은정상이다. 이러한검사결과는전정소뇌를포함한정중선소뇌 (midline cerebellum) 의이상을의미하며이는두질환의주된원인인칼슘통로 CACNA1A 유전자가소뇌의 purkinje cell 및 granular cell에풍부히존재한다는사실과도일치하며뇌자기공명영상소견상충부 (vermis) 를포함한정중소뇌의위축이흔히발견되는점과도일치되는소견이다. 19 5. 편두통과연관되면서반복되는현훈 1) 메니에르병 12 1861년메니에르가처음으로이질환을기술할당시그는메니에르병과편두통은반복적인현훈의흔한원인질환이고두질환이한환자에서동시에나타날수있다는것을알았다. 하지만이러한점이두질환의임상양상의유사성에따른단순히진단기준의중복이의한것인지, 두질환의발병기전의근본적인유사성이있는지는아직까지명확하지않다. 또한현재까지도이들두질환을확진할수있는특이적인진단방법이없다는점도두질환간의분명한관계를규명하는데어려움이된다. 메니에르병에서편두통의빈도는일반인구에비해 2배정도높으며, 편두통을가진환자에서메니에르병의빈도 (7.5%) 가일반인에서의메니에르병의유병률 (0.05%) 에비해월등히높은것으로알려져있다. 메니에르병과의상관관계를설명할수있는하나의가설로서 편두통의발병기전의하나인혈관연축이내림프관및내림프낭에허혈성손상을일으켜서서히내림프액의흡수장애가일어나며이로부터수년후메니에르증후군의일종인지연성내림프수종 (delayed endolymphatic hydrops) 을일으킨다는주장이있다. 2) 양성돌발현훈양성돌발성두위현훈은현훈의가장흔한원인질환중의하나이며, 편두통환자에서관찰되는현훈의원인질환중에서도가장큰비중을차지한다. 이는편두통환자에서단순히두통과반복적인현훈이있다하여쉽게편두통성현훈으로진단할수없다는점을의미한다. Neuhauser 등 1 의연구결과에따르면편두통과어지럼을가진 75명의환자에서단지 19명만최종적으로편두통성현훈으로진단되고나머지환자들은다른신경이과적질환으로진단되었으며이들중가장흔한질환 (28%) 은바로양성돌발성두위현훈이었다. 또한후반고리관기원의비외상성양성돌발성두위현훈환자의 32% 는편두통의병력이있어대조군에비해 (16%) 유의하게높았다. 이러한연구결과를토대로볼때편두통과현훈의단순조합이편두통성현훈의진단에충분하지는않지만편두통환자에서는양성돌발성두위현훈의빈도가일반인에비해높음을또한알수있다. 그발병기전에관해확실하게알수는없지만편두통에동반되는혈관연축이내이의난형낭에손상을주어이석이떨어져나오기때문에발생하는것으로추측하고있다. 임상적으로는젊은연령층에서양성돌발성두위현훈이특별한원인인자없이나타나며적절한수기를통해치료하였음에도불구하고여러번재발할때한번쯤편두통이원인인자로작용할가능성을생각해보아야할것이다. 13 결론일상생활을저해할정도의현훈이반복적으로발생하면서, 편두통이있고, 혹두통이없더라고, 현훈발작에편두통에수반되는증상이동반되거나두통유발요인에의해현훈이영향을받으면서, 다른원인으로어지럼을설명할수없을때편두통성현훈으로진단할수있다. 아직, 편두통성현훈의국제적인진단기준은제시되지않은상태로병력청취를근거로하고, 다른질환을배제하는과정을통해내려지는진단이라는제한점이있기는하나, 대표적인재발현훈이며, 일부편두통치료에의해호전을보이는점등을볼 49
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