A 48-year-old woman was admitted to our department with recurrent episodes of throbbing right parietal headache lasting for hours. The patient was afebrile and neurologic examination disclosed no signs of meningeal irritation or papilledema. Blood pressure (BP) levels and heart rate were normal (140/90 mm Hg, 70 bpm) on repeat measurements.

48歲女性主因反復(fù)發(fā)作性搏動(dòng)性右頂部頭痛數(shù)小時(shí)收入我科?；颊邿o(wú)發(fā)熱，神經(jīng)系統(tǒng)查體無(wú)腦膜刺激征及視乳頭水腫。重復(fù)測(cè)量血壓和心率正常（140/90 mm Hg, 70 次/分）。

Before onset of headache she experienced a transient sensory deficit on the right half of her body. The patient reported having the first episode of headache 2 weeks prior to admission, while on a trip in Colombia. The pain was of pulsating nature and was aggravated by physical activity. She occasionally reported that the headache was accompanied by nausea, vomiting, allodynia of the skin of the head, and phonophobia  and  photophobia. The headache attacks were not preceded by any symptoms of aura and were relieved by nonsteroid inflammatory drugs followed by periods of rest and sleep. The headache episodes lasted less than 24 hours and the patient recovered completely from her symptoms. The patient had no history of headaches and no family history of migraine.

頭痛發(fā)作前患者有短暫性的右側(cè)肢體感覺(jué)缺失?；颊咴V入院前2周在哥倫比亞旅行時(shí)首次發(fā)生頭痛。疼痛呈搏動(dòng)性，體力活動(dòng)加重。頭痛偶伴有惡心嘔吐，頭皮異常疼痛和畏聲畏光。頭痛前無(wú)先兆癥狀，服用非甾體類抗炎藥物然后休息或睡眠可以改善。頭痛發(fā)作不超過(guò)24小時(shí)，患者癥狀可以完全緩解?；颊呒韧鶡o(wú)頭痛史，無(wú)偏頭痛家族史。

Questions for consideration:

1. What is your differential diagnosis at this time point?

2. What additional diagnostic tests would you consider at this time point?

思考問(wèn)題:

1、鑒別診斷是什么？

2、此時(shí)還需要哪些輔助檢查協(xié)助診斷？

The differential diagnosis included meningoencephalitis, temporal arteritis, cerebral venous sinus thrombosis (CVST), intracranial bleeding, reversible vasoconstriction syndrome, and posterior reversible encephalopathy.

鑒別診斷包括腦膜腦炎、顳動(dòng)脈炎、腦靜脈竇血栓 (CVST)、顱內(nèi)出血、可逆性血管收縮綜合征和可逆性后部腦病綜合征。

The patient underwent immediate brain MRI during her present hospitalization. Axial T2, fluid attenuated inversion recovery, T1-weighted imaging, 2-dimensional time-of-flight cerebral magnetic resonance angiography (MRA), and diffusion-weighted imaging sequences were negative for acute cerebral ischemia, posterior reversible encephalopathy, vasoconstriction syndrome, and intracerebral bleeding, and no signs of CVST were observed.

患者入院后立即行頭MRI檢查。軸位T2FLAIR，T1加權(quán)像、2維TOF MRA和DWI成像無(wú)急性腦缺血、可逆性后部腦病、血管收縮綜合征和顱內(nèi)出血的表現(xiàn)，也未見(jiàn)CVST的征象。

The initial EEG showed slowing over both occipital lobes with no epileptiform activity (figure, A). The duplex and Doppler sonography of the cerebral vessels and the external temporal artery revealed no signs of cerebral vasospasm or temporal arteritis (halo sign). The CSF examination documented a lymphocytic pleocytosis with 14 cells (100% lymphocytes), normal protein (462 mg/L), pressure (60 mm H2O), glucose (85 mg/dL), and lactate (16 mg/dL). HIV, syphilis, and sarcoidosis testing (angiotensin-converting enzyme in serum and CSF, chest X-ray) were negative and cytology/flow cytometry studies had normal results. The patient was placed on IV acyclovir medication at dosage of 3 × 10 mg/kg body weight until we received the negative CSF PCR results of herpes simplex virus 1 and 2, varicella zoster, cytomegalovirus, and Epstein-Barr.

最初的腦電圖提示雙枕葉慢波無(wú)癲癇樣電活動(dòng)（圖A）。腦血管和外部顳動(dòng)脈的雙功能多普勒超聲提示無(wú)腦血管痙攣或顳動(dòng)脈炎的表現(xiàn)（暈環(huán)征）。腦脊液檢查提示淋巴細(xì)胞14個(gè)（100%淋巴細(xì)胞），蛋白（462 mg/L)、顱壓(60 mm H2O)、葡萄糖(85 mg/dL)和乳酸(16 mg/dL)正常。HIV、梅毒和結(jié)節(jié)病檢查（血清和腦脊液血管緊張素轉(zhuǎn)化酶，胸片）都陰性，細(xì)胞學(xué)/流式細(xì)胞分析結(jié)果正常。在腦脊液?jiǎn)渭儼捳畈《?型和2型、帶狀皰疹病毒、巨細(xì)胞病毒和EB病毒PCR陰性結(jié)果出來(lái)之前，給予患者靜點(diǎn)阿昔洛韋（無(wú)環(huán)鳥苷）3× 10mg/Kg。

Question for consideration:

1. Which is the final diagnosis?

思考問(wèn)題：

1、最終診斷什么？

Her neurologic condition was attributed to a pseudomigraine with transient neurologic deficit and lymphocytic pleocytosis. Consequently she received an IV therapy with 250 mg methylprednisolone/day. The pseudomigranous headache improved substantially within 48 hours. Repeat EEG was then normal (figure, B).

患者神經(jīng)系統(tǒng)表現(xiàn)考慮合并有短暫性神經(jīng)系統(tǒng)功能缺損和淋巴細(xì)胞性細(xì)胞數(shù)增多的假性偏頭痛。因此給予靜點(diǎn)甲強(qiáng)龍250mg /天治療。48小時(shí)內(nèi)這種假性偏頭痛性頭痛基本緩解。復(fù)查腦電圖正常（圖B）

The patient fulfilled the criteria of the International Headache Society for the syndrome of transient headache and neurological deficits with CSF lymphocytosis (HaNDL), which should always be considered in the differential diagnosis of headache with transient neurologic symptoms. The diagnostic criteria consist of 1) episodes of moderate to severe headache lasting hours before resolving fully, 2) CSF pleocytosis with lymphocytic predominance (>15 cells/L) and normal neuroimaging, CSF culture, and other tests for etiology, 3) episodes of headache are accompanied by or shortly follow transient neurologic deficits and commence in close temporal relation to the development of CSF pleocytosis, 4) episodes of headache and neurologic deficits recur over 3 months.¹

患者符合國(guó)際頭痛協(xié)會(huì)關(guān)于短暫頭痛、神經(jīng)功能缺損伴腦脊液淋巴細(xì)胞增多綜合征(HaNDL)的診斷標(biāo)準(zhǔn)，在頭痛伴有短暫神經(jīng)系統(tǒng)癥狀的鑒別診斷中應(yīng)該考慮此病。診斷標(biāo)準(zhǔn)包括：1）發(fā)作性中重度頭痛持續(xù)數(shù)小時(shí)后可完全緩解，2）腦脊液細(xì)胞數(shù)增多，以淋巴細(xì)胞為主（大于15 個(gè)細(xì)胞/升），影像學(xué)、腦脊液培養(yǎng)和其它病因?qū)W檢查正常，3）頭痛發(fā)作伴隨或在短暫神經(jīng)系統(tǒng)功能缺損后出現(xiàn)，并與腦脊液淋巴細(xì)胞增多有時(shí)間關(guān)聯(lián)性，4）頭痛和神經(jīng)功能缺損在3個(gè)月內(nèi)復(fù)發(fā)。¹

Our diagnostic evaluation in combination with the patient’s history excluded other causes of transient neurologic dysfunction accompanied by headache including meningoencephalitis, CNS vasculitis, intracranial bleeding, reversible vasoconstriction syndrome, posterior reversible encephalopathy, and CVST. This can be tricky especially in the case of the reversible vasoconstriction syndrome and convexal subarachnoid hemorrhage where extensive radiologic workup is necessary (MRI with diffusion-weighted images, fluid-attenuated inversion recovery, T1- weighted imaging, 2-dimensional time-of-flight cerebral MRA, transcranial Doppler ultrasonography, and conventional transfemoral angiography)。

結(jié)合輔助檢查和患者的病史排除了引起短暫神經(jīng)系統(tǒng)功能缺損伴有頭痛的其他原因，包括腦膜腦炎，CNS血管炎，顱內(nèi)出血，可逆性血管收縮綜合征，可逆性后部腦病和顱內(nèi)靜脈系統(tǒng)血栓。這可以很復(fù)雜，尤其在可逆性血管收縮綜合征和凸面蛛網(wǎng)膜下腔出血的病例中可能需要行大量的影像學(xué)檢查（磁共振彌散加權(quán)成像，F(xiàn)LAIR、T1加權(quán)成像、2維TOFMRA、經(jīng)顱多普勒超聲和常規(guī)的經(jīng)股動(dòng)脈血管造影檢查）。

Several reports of this syndrome used various terms including headache with neurologic deficits and CSF pleocytosis² and pseudomigraine with temporary neurologic symptoms and lymphocytic pleocytosis. ^3,4 Patients with this condition are usually men between 15 and 40 years of age.

幾個(gè)關(guān)于此綜合征的報(bào)道使用了不同的名稱，包括伴有神經(jīng)功能缺損和腦脊液細(xì)胞數(shù)增多的頭痛以及伴有短暫神經(jīng)系統(tǒng)癥狀和淋巴細(xì)胞性細(xì)胞數(shù)增多的假性偏頭痛。此病常見(jiàn)于15-40歲男性。

The self-limited syndrome consists of 1 to several episodes of variable neurologic deficits accompanied by moderate to severe headache and in some cases fever. Each episode lasts hours, with total duration of the syndrome being from 1 to 70 days. The neurologic manifestations, involving either cerebral hemisphere or the brainstem/cerebellum, are most commonly sensory symptoms (78% of reported cases), aphasia (66%), and motor deficits (56%). Migraine aura–like visual symptoms are relatively uncommon (18%).¹ CSF abnormalities include a lymphocytic pleocytosis (10–760 cells/L), elevation of CSF protein (20–250 mg/dL) in>90% of cases, and increased CSF opening pressure (100–400 mm H₂O] in>50% of cases).^1,5,6 MRI and CT are invariably normal, but EEG often shows focal or diffuse slowing. SPECT studies demonstrate focal or widespread areas of decreased blood flow on the side of origin of the neurologic deficits, suggestive of the spreading depression-like mechanism similar to that proposed for migraine. Results of the microbiologic studies are always negative.^7,8

該綜合征具有自限性，可有1到數(shù)次表現(xiàn)不同的神經(jīng)缺損癥狀伴有中重度頭痛，部分病人合并發(fā)熱。每次發(fā)作持續(xù)數(shù)小時(shí)，總發(fā)病時(shí)間是1至70天。神經(jīng)系統(tǒng)癥狀，包括累及大腦半球或累及腦干/小腦所致的，最常見(jiàn)的是感覺(jué)癥狀（78%報(bào)道的病例）、失語(yǔ)（66%）和運(yùn)動(dòng)缺損癥狀（56%）。偏頭痛先兆樣癥狀相對(duì)少見(jiàn)（18%）。腦脊液的異常有淋巴細(xì)胞為主的白細(xì)胞增多（10–760 個(gè)細(xì)胞/升），90%以上的病例蛋白增高（20–250 mg/dL），腦脊液壓力增高（超過(guò)50%的患者在100-400mm水柱）。MRI和CT總是正常的，但腦電圖常顯示局灶性或彌漫性慢波。SPECT顯示局灶性或廣泛的血流下降區(qū)，位于引起神經(jīng)功能缺損的那側(cè)腦區(qū)，提示存在擴(kuò)散抑制樣機(jī)制，與以前提出的偏頭痛機(jī)理類似。微生物學(xué)研究結(jié)果總是陰性的。

The cause of the syndrome is unclear, although there are numerous theories like the infectious-autoimmune, neurogenic inflammation, dysfunction of the blood– brain barrier, spread cortical depression, and trigeminous-vascular activation.^3,5 Pseudomigraine with temporary neurologic symptoms and lymphocytic pleocytosis could result from an activation of the immune system secondary to a recent viral infection, which would produce antibodies against neuronal or vascular antigens. This autoimmune attack may induce an aseptic leptomeningeal vasculitis causing a CSF pleocytosis and accounting for the headache and the transient symptoms likely through a spreading depression-like mechanism.

該綜合征病因不清，有許多假說(shuō)，如感染-自身免疫、神經(jīng)源性炎癥、血腦屏障功能障礙、擴(kuò)散皮層抑制和三叉神經(jīng)血管系統(tǒng)激活機(jī)制等。假性偏頭痛伴有短暫神經(jīng)系統(tǒng)癥狀和淋巴細(xì)胞為主的白細(xì)胞增多癥可能是由于繼發(fā)于近期病毒感染引起的免疫系統(tǒng)的激活，產(chǎn)生了針對(duì)神經(jīng)元或血管抗原的抗體。這種自身免疫攻擊可能通過(guò)擴(kuò)散抑制機(jī)制誘發(fā)無(wú)菌性軟腦膜血管炎引起腦脊液細(xì)胞數(shù)增多，導(dǎo)致頭痛和短暫的癥狀。

Some obvious similarities to migraine with aura exist.⁹ In migraine vasodilator peptides such as calcitonin gene-related peptide (CGRP), substance P, neurokinin A, neuropeptide Y (NPY), and galanin are found in trigeminal neurons and could be involved in vascular nociception, supporting the neurogenic inflammation theory that proposes CGRP release from trigeminal sensory afferents causing vasodilation and plasma extravasation from dural vessels. This procedure may lead to a “sterile neurogenic inflammation.”¹⁰ However, the duration of the focal symptoms in migraine is longer than in HaNDL. The most important difference between migraine and HaNDL is the CSF pleocytosis.

與伴有先兆的偏頭痛有明顯的相似之處。在偏頭痛中，三叉神經(jīng)中發(fā)現(xiàn)有血管擴(kuò)張肽如降鈣素基因相關(guān)肽（CGRP)、P物質(zhì)、神經(jīng)激肽A、神經(jīng)肽Y（NPY）和甘丙肽，可能參與到血管損傷，支持神經(jīng)源性炎癥假說(shuō)，提出CGRP從三叉神經(jīng)感覺(jué)傳入纖維釋放出來(lái)引起血管擴(kuò)張，并使血漿從硬膜血管中溢出。該過(guò)程可能導(dǎo)致“無(wú)菌的神經(jīng)源性炎癥”。但是偏頭痛中局灶性癥狀的持續(xù)時(shí)間比HaNDL要長(zhǎng)。兩者最重要的區(qū)別是腦脊液中細(xì)胞數(shù)異常增多。

The present case highlights the importance of diagnosing the syndrome of transient HaNDL in patients with or without history of migraine with transient neurologic deficits. The diagnosis of HaNDL is one of exclusion, as extensive paraclinical testing should be obtained to exclude other differential diagnoses.

本例強(qiáng)調(diào)了在有或無(wú)偏頭痛病史伴有一過(guò)性神經(jīng)功能缺損患者中診斷短暫性HaNDL綜合征的重要性。HaNDL綜合征的診斷是一種排除性診斷，因?yàn)閼?yīng)行大量的臨床特異性檢查來(lái)除外其它的鑒別診斷。

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