HIV患者头痛的诊治

译者：解曼青博士

北京协和医院神经科

北京市东城区帅府园1号

100730

Email：mia_1210@yahoo.com.cn

校对者：关鸿志博士

北京协和医院神经科

北京市东城区帅府园1号

100730

Headache is common during all stages of infection with the Human Immunodeficiency Virus (HIV), from seroconversion to the development of an AIDS related illness. The majority of headaches in HIV seropositive persons are due to primary headache syndromes, such as migraine and tension type headaches. However, a headache can also portend life-threatening illness such as an opportunistic infection (OI) or neoplasm arising in the setting of impaired cellular immunity. It is therefore important to recognize when a serious central nervous system (CNS) disease may be present and when a detailed evaluation is necessary.

头痛在HIV感染的血清转化期至AIDS期的各个阶段都较常见。大部分HIV血清阳性患者头痛的原因为原发头痛综合征，如偏头痛或紧张性头痛。但是头痛也可预示着威胁生命的严重疾病，比如机会性感染或由于细胞免疫功能减弱所致的肿瘤。因此认识到何种情况下可能为中枢神经系统的严重疾病，何时有必要进一步详细评估，是重要的。

This chapter will review the epidemiology of headache, the clinical presentations of CNS infections and neoplasms that may cause headache, the evaluation of headache in an HIV seropositive patient, treatment of HIV-associated headache and the changes in frequency and etiology of headache since the introduction of highly active antiretroviral therapy (HAART).

这一章节将回顾头痛的流行病学，CNS感染和肿瘤所导致头痛的临床表现，HIV血清阳性患者头痛的评估，HIV相关头痛的治疗，及高效抗逆转录病毒治疗（HAART）后头痛频度及病因方面的变化。

Headache is common. In studies of the general population, the lifetime prevalence for any type of headache ranges from 69 to 99% (Table 1). Central nervous system disease is uncommon in people presenting to an emergency room or medical clinic for evaluation of headache (Table 2). In one prospective study of patients with brain tumor, only 8% of patients reported headache as the first clinical manifestation of disease (92). In retrospective studies, 48 to 71% of people with brain tumor reported headache at some time during illness (37, 91). Predicting which headache is due to a pathological condition is difficult. Although headaches in people with CNS neoplasms have traditionally been associated with early morning occurrence, a positional or unilateral nature, or nausea and vomiting, none of these attributes, in and of itself, is specific for underlying CNS disease.

头痛很常见。对普通人群的研究发现，一生中各种类型的头痛出现的概率在69-99%间（表1）。对于急诊或门诊就诊进行评估的头痛患者，中枢神经系统疾病并不常见（表2）。在一项脑肿瘤患者的前瞻性研究中发现，只有8%的患者首先出现的临床表现是头痛（92）。在回顾性研究中，发现48-71%的脑部肿瘤患者在其病程中出现过头痛（37，91）。预知何种头痛是器质性疾病所致是比较困难的。虽然CNS肿瘤患者的头痛传统上认为具有晨起多见、位置相对固定和单侧痛的特性，可伴有恶心和呕吐，但这些对潜在的CNS疾病均不特异。

Headache is the most common form of pain in HIV seropositive persons, more common than painful peripheral neuropathy, and has been reported in 22.7% of people newly diagnosed with AIDS (41) and in up to 55% of HIV seropositive patients (50).

头痛是HIV血清阳性患者出现的疼痛中最常见的形式，较周围神经痛更多见，有报道在22.7%的新近诊断AIDS的人群（41）和55%的HIV血清阳性患者（50）均可出现头痛。

Both primary headache, such as migraine or tension-type headache, and secondary headache, such as those caused by opportunistic infections or neoplasms, affect HIV seropositive people. Brew and Miller proposed “HIV headache” as a new term to describe a headache that develops during HIV infection and is similar to HIV aseptic meningitis except without CSF pleocytosis (15). In their retrospective study, they found that 18 of 312 (5.8%) HIV positive patients (mean CD₄ count 58.9 cells/mm3) but only 2 of 971 (0.2%) HIV negative patients had unexplained headache.

偏头痛或紧张性头痛等原发性头痛，及机会性感染或肿瘤导致的继发性头痛，均可见于HIV血清阳性的人群。Brew和Miller提议“HIV头痛”作为描述HIV感染所致头痛得一个新术语，就像无脑脊液白细胞增多的HIV无菌性脑膜炎（15）。在他们的回顾性研究报道，312名HIV阳性患者（mean CD₄ count 58.9 cells/mm3）中有18名（5.8%），而971名HIV阴性患者中有2名（0.2%），出现原因不明的头痛。

The prevalence rates of headache during HIV infection vary from 3.8% to 47.4% depending on the design of the study, the criteria for headache, the subgroup of patients enrolled and the stage of the disease (11, 51).

HIV感染所致头痛的患病率由于研究设计、头痛的诊断标准、入组病人的群体和疾病阶段的不同，波动在3.8至47.4%之间。（11，15）。

Headache is common during asymptomatic HIV infection and may be more prevalent following the development of acquired immunodeficiency syndrome (AIDS). In a prospective two-year study, asymptomatic HIV seropositive men reported twice as many new headaches as HIV seronegative men (4.4% vs 2.1%, p = 0.001) (51). People with symptomatic HIV infection or AIDS report headache more often than people with asymptomatic HIV infection (48). In one prospective study, people with AIDS reported more than three times as many headaches as HIV seropositive people without AIDS (39% vs. 11%, p = 0.0001), and progression from asymptomatic to symptomatic HIV infection was associated with an increased incidence of headache (86). In the Women’s Interagency HIV study, the prevalence of self-reported headache was lower in HIV-seronegative women (21.8%) than in seropositive women. Among seropositive women, headache prevalence did not differ significantly between women receiving HAART (26.2%) and women not receiving HAART (29.1%) (85). Primary headache in HIV seropositive people was evaluated in one study that found a prevalence of migraine of 16% and tension type headache of 45.8%. The same study suggested a decrease in the frequency of migraines during progression of the disease (95).

头痛在HIV感染的无症状期很常见，但在相继出现的获得性免疫缺陷综合征期（AIDS）有可能更加普遍。在一项为期2年的前瞻性研究中发现，HIV血清阳性但无症状的人群新发头痛出现的概率是HIV血清阴性人群的2倍(4.4% vs 2.1%, p = 0.001) (51)。有症状的HIV感染人群和AIDS人群较无症状的HIV感染人群更多出现头痛(48) 。在一项前瞻性研究中发现，AIDS人群出现头痛的概率比HIV血清阳性但无AIDS的人群高3倍(39% vs. 11%, p = 0.0001)，并且HIV感染从无症状至有症状的发展过程中，头痛患病率会逐渐升高(86)。在一项女性的Interagency HIV研究中，HIV血清阴性女性自述头痛的患病率（21.8%）较血清阳性组低。在血清阳性的女性中，接受HAART治疗的（26.2%）较未接受HARRT治疗的女性(29.1%)出现头痛的患病率差异并不显著(85)。一项研究对HIV血清阳性人群的原发性头痛进行了评估，发现偏头痛患病率为16%，紧张性头痛患病率为45.8%。此项研究还发现在疾病的进程中偏头痛出现的概率逐渐减少(95)。

The proportion of headache due to opportunistic infection or neoplasm varies with sociodemographics, risk factors for HIV infection and stage of illness. In a study by Lipton and colleagues, 82% of HIV seropositive people presenting to an AIDS clinic or emergency room for evaluation of new onset headache had a CNS mass lesion or meningitis (56). This was from a cohort of 49 patients, 59% of which were intravenous drug users (IVDU), 8% were Caucasian, 33% African American and 55% Hispanic. 84% had AIDS. Another study of HIV seropositive patients presenting to an outpatient clinic with headache found a “focal brain lesion” or meningitis in only 6/93 (6.5%) (38). In this group, 34% were IVDU, 69% were Caucasian, 16% African American, 10% Hispanic and 62% had no previous AIDS opportunistic infection.

机会性感染或肿瘤导致头痛的比例会由于社会人口统计学，HIV感染的高危因素以及疾病分期的不同而不同。在Lipton等的研究中发现，因新发头痛于AIDS门诊或急诊就诊的HIV血清阳性的人群，其中82%发现有CNS占位性病变或脑膜炎(56)。这是一项49个病人的队列研究，59%是静脉药物使用者(IVDU)，8%是高加索人，33%是非洲裔美国人，55%是西班牙裔，其中84%是AIDS患者。另一项对因头痛而至门诊就诊的HIV血清阳性的患者的研究中发现，仅有6/93 (6.5%)的患者有“局灶脑病变”或脑膜炎(38)。在此项研究中，34%是IVDU，69%是高加索人，16%是非洲裔美国人，10%是西班牙裔，62%之前无机会性感染。

With the dramatic change in therapeutic options for HIV treatment and prophylaxis of OI, the epidemiology of headache in HIV seropositive persons has also changed. Since the introduction of HAART, the incidence of opportunistic infections has significantly decreased. AZT was licensed in 1987, ddI in 1991. In San Francisco, the proportion of individuals living with AIDS who received HAART increased from 5% in 1995 to 76% in 2003. The incidence of CNS infections among these individuals was 6% per year in 1995 and less than 1% per year in 2003 (30).

由于HIV治疗及机会性感染的预防方面的巨大改变，HIV血清阳性人群头痛的流行病学亦有改变。HAART的应用使得机会性感染的概率显著降低。AZT是1987年注册的，ddI是1991年注册的。在旧金山，接受HAART的AIDS人群的比率从1995年的5%增加至2003年的76%。1995年上述人群中CNS感染的发病率为每年6%，2003年降至不到1%(30)。

A low absolute CD₄ count is the most important risk factor for development of an opportunistic CNS infection or neoplasm. Graham and colleagues reviewed 204 CT scans in 178 HIV seropositive patients presenting with headache but without altered mental status, meningeal signs, neurological findings or symptoms of subarachnoid hemorrhage (44). They found that all mass lesions or white matter lesions occurred in patients with CD₄ counts of <200cells/mm³.

CD4绝对数量的减少是CNS出现机会性感染或肿瘤最重要的危险因素。Graham等对178名HIV血清阳性患者进行了204次CT扫描，这些患者均有头痛，但尚无神志改变、脑膜炎及蛛网膜下腔出血的症状及体征(44)。他们发现占位性病变或白质病变仅出现在CD4数量<200cells/mm³的患者中。

Cryptococcal meningitis, TE, progressive multifocal leukoencephalopathy (PML), primary CNS lymphoma, AIDS dementia complex, and cytomegalovirus encephalitis are all uncommon when the CD₄ count is greater than 200 cells/mm³. The incidence of each of these infections increases as the CD₄ count drops from 200 cells/mm³ to 100 cells/mm³ or less (8, 76).

隐球菌性脑膜炎，弓形体脑炎，进行性多灶性白质脑病(PML)，原发性中枢神经系统淋巴瘤，AIDS痴呆综合症和巨细胞病毒脑炎在CD4数量高于200　cells/mm³时很少出现。上述感染在CD4细胞数降至100 cells/mm³至200 cells/mm³甚至更低时出现的机率会增加(8, 76)。

However, as new treatments are developed, prophylaxis and life expectancy are changing; one study found a dramatic decrease in the incidence of HIV dementia, cryptococcal meningitis, and lymphoma after the introduction of HAART, but also noted an increased proportion of new cases of HIV dementia in people with a CD₄ count in a higher range, i.e. 201-350 (83).

但是随着新治疗手段的进展，预防性治疗及生存期方面也相应变化；一项研究发现随着HAART治疗的运用，HIV痴呆、隐球菌脑炎和淋巴瘤出现的发生率显著降低，但是也发现了有较高CD4数量（201-350）的人群中新发HIV痴呆的比率有所增高(83)。

Approximately 10% of AIDS patients with cerebral toxoplasmosis or PML have CD₄ cell counts >200 cells/mm³ (12).

大约10%的患有大脑弓形体病或PML的AIDS患者的CD4细胞数大于200 cells/mm³ (12)。

The CD₄ count may be misleading during the immune reconstitution inflammatory syndrome (IRIS), whereby a subgroup of patients will exhibit a paradoxical deterioration in their clinical status despite increase in their CD₄ count, shortly after initiating HAART. It is thought to result from an exaggerated inflammatory response towards latent opportunistic pathogens.

在免疫重建综合症(IRIS)时，有些病人在刚接受HRAAT后，虽然CD4数量有所增加，但其临床症状却加重了。这种现象目前认为是由潜伏的机会性感染病原体所致的过激的免疫反应引起。

Most opportunistic CNS infections and neoplasms are due to reactivation of previously acquired infections. In the United States, 10% to 40% of people with AIDS are latently infected with Toxoplasma gondii, as determined by presence of anti-Toxo immunoglobulin G (IgG) antibodies in serum. In France, the seroprevalence of anti-Toxo IgG in people with AIDS is 80%. At least one-third of people with anti-Toxo IgG antibodies will develop TE (60).Up to 22% of people with biopsy proven TE will not have serum IgG antibodies against Toxoplasma gondii (22, 74). IgM antibodies to Toxoplasma gondii are rarely present in patients with TE. The incidence of TE is reduced in people who take TMP/SMX or dapsone/pyrimethamine as prophylaxis against Pneumocystis carinii pneumonia (16, 18).

大部分中枢神经系统感染或肿瘤都是由之前的潜伏感染的再燃所致。在美国，通过血清抗弓形体抗体IgG的测定发现大约10-40%的AIDS患者有弓形体的隐性感染。法国的AIDS人群中血清弓形体抗体IgG的阳性率是80%。至少1/3的血清抗体阳性的人群会发展至弓形体脑炎(60)。但约22%的经活检证实的弓形体脑炎患者血清中未发现弓形体的IgG抗体(22, 74)。抗弓形体的IgM抗体在患者中鲜有发现。服用预防肺囊虫肺炎的TMP/SMX或氨苯砜／乙胺嘧啶的人群出现弓形体脑炎的概率会有所降低(16, 18)。　

Cryptococcus neoformans is a ubiquitous yeast that causes meningitis in 7% of people with AIDS (22). In people with cryptococcal meningitis, Cryptococcal polysaccharide capsular antigen (CrAg) is detectable in 99% of serum and 91% of cerebrospinal fluid (CSF) samples (75). Thus, in a patient with negative serum CrAg, the diagnosis of cryptococcal meningitis is virtually excluded.

新型隐球菌是一种广泛分布的酵母菌，可以在7%的AIDS患者中导致脑膜炎(22)。在隐球菌脑膜炎的患者中，隐球菌多糖荚膜抗原(CrAg)在99%的血清标本和91%的脑脊液标本中均可测出(75)。因此血清CrAg阴性者，基本可以排除隐球菌脑膜炎的诊断。

Reactivation of latent viral infection is also associated with CNS disease. Epstein-Barr virus (EBV) is present in the CSF up to 100% of patients with primary CNS lymphoma (24). JC virus is present in the CSF of 92% of people with PML (64). The majority of people in the United States have serum antibodies against EBV and JC (20, 33). Presence of EBV or JC antibodies in the serum is not associated with increased incidence of either primary CNS lymphoma or PML.

病毒隐性感染的再燃也与CNS疾病有关。EBV在原发性中枢神经系统淋巴瘤患者的脑脊液中出现率高达100%(24)。JC病毒在PML人群的脑脊液中阳性率为92%(64)。美国的大部分人群的血清抗EBV和JC抗体是阳性的(20, 33)。血清中出现抗EBV和JC抗体并不增加罹患原发性中枢神经系统淋巴瘤或PML的概率。

CMV infection fell precipitously after the introduction of HAART (from 20.9 per 100 person years to 3.5 after introduction of HAART) and occurs primarily in people with CD₄ count below 50 cells/mm³,(9).

随着HAART的应用，CMV感染的概率急剧下降（从每年每100人中有20.9人降至3.5人），主要出现在CD4细胞数低于50 cells/mm³的人群(9)。

鼻窦炎是导致头痛的常见原因。HIV感染人群鼻窦炎的患病率为10-35%，在AIDS人群中更加常见(73, 82, 88)。肺炎链球菌、流感嗜血杆菌和卡他莫拉菌是最常见的导致急性细菌性鼻窦炎的病原菌，但是由非典型致病细菌如铜绿假单胞菌、李斯特菌或真菌类的交链孢霉属、曲霉属、假丝酵母、隐球菌、假霉样真菌和根霉菌所致的鼻窦炎在HIV感染的人群中亦有报道(65, 66)。非感染性或者过敏性鼻窦炎也不少见。

Although headache is listed as a potential side effect of almost every HIV medication, there have been few studies directly addressing the relationship of antiretrovirals with headache. Studies investigating the reason for discontinuing HAART therapy found adverse reactions were reported in 22% to 46.1% of people, but headache was not usually the major adverse reaction (4, 59, 68).

虽然头痛被列为几乎所有HIV药物潜在的副作用，但是少有关于抗逆转录病毒与头痛之间关系的研究。一项关于终止HAART的研究发现22-46.1%的人群在接受HAART时会出现不良反应，但是头痛不是常见的主要不良反应(4, 59, 68)。

In one study, 16% of persons taking zidovudine (AZT) developed headache (86). Amprenavir has also been associated with headache (3). When AZT was used as a single agent and doses were higher, headache was reported more often. In a study of primary headache in HIV seropositive patients, Mirsattari and colleagues found that neither use nor discontinuation of HAART affected development or progression of migraine, tension type headaches or cluster headaches (67). In the Women’s interagency HIV study, headache was not significantly different in seropositive women taking or not taking HAART (26.2% vs 29.1%, respectively) (85).

有研究报道16%的服用齐多夫定(AZT)的人群出现了头痛(86)。安普那韦被认为与头痛也有一定关系(3)。当AZT被做为单一药物使用或剂量较大时，头痛更易出现。在一项HIV血清阳性患者的原发性头痛的研究中，Mirsattari等发现应用或终止HAART均不会影响偏头痛、紧张性头痛或丛集性头痛的发生和进展(67)。在女性interagency HIV研究中发现，接受或不接受HAART的血清阳性的女性，其头痛并无显著差异(26.2% vs 29.1%) (85)。

甲氧苄氨嘧啶/磺胺甲恶唑 (TMP/SMX)，作为弓形体脑炎和卡式肺囊虫肺炎的预防用药，被认为与部分头痛和无菌性脑膜炎有关(47)。

Some medications can exacerbate old headache or induce new headache (Table 5). Chronic usage of medication and other substances, such as caffeine, can induce a "rebound" headache. Illicit drugs most often associated with headache include heroin and cocaine (31, 32, 58). Detoxification from heroin, cocaine or marijuana, as well as from licit medications, is also associated with headache (28).

一些药物可加重原有的头痛或诱发新发头痛(Table 5)。药物或其他物质如咖啡因的慢性使用，可诱发一种“回弹性”头痛。最长见的和头痛相关的非法药物包括海洛因和可卡因(31, 32, 58)。在戒断海洛因、可卡因、大麻或中断某些合法药物治疗的过程中，也常伴发头痛(28)。

The International Headache Society classifies headaches according to their characteristics, such as migraine, tension type and chronic daily headaches (Table 6) (1). Primary headaches are the most common headache type in HIV-infected patients. In a study of 115 HIV positive patients, 44 (35%) of whom had headaches, 29 were due to primary headaches (22 migraine, 4 tension type, 3 cluster) and the remaining 15 had a “secondary cause” (67).

国际头痛协会根据头痛性质将其分类，如偏头痛、紧张性头痛和慢性日间头痛(Table 6) (1)。原发性头痛是HIV感染患者最常见的头痛类型。在一项对115名HIV阳性患者的研究中发现，44名(35%)有头痛，其中的29名是由原发性头痛所致（22名偏头痛，4名紧张性头痛，3名从集性头痛），剩余的15名是继发性所致(67)。

HIV infection may predispose to the development or exacerbation of primary headaches, and these often do not respond to conventional management (67). Common comorbidities such as depression, anxiety, substance abuse or withdrawal, polypharmacy and insomnia, frequently contribute to the development of headaches and may, in turn, be aggravated by them.

HIV感染可能导致原发性头痛的发展及恶化，并且对常规治疗反应不佳(67)。常见的并发症如抑郁、焦虑、毒品滥用或戒断、服药过量和失眠，会加快头痛的进展，头痛亦会加重上述症状。

There are many potential etiologies of headache in an HIV seropositive person. Headache has been associated with primary HIV infection, opportunistic CNS infection, neoplasm, HIV pharmacotherapy, as well as substance abuse, systemic infection and migraine (Table 3).

HIV血清阳性患者的头痛具有很多潜在的病因。头痛被认为与原发性HIV感染、机会性中枢神经系统感染、肿瘤、HIV药物治疗以及毒品滥用、全身感染和偏头痛相关(Table 3)。

When evaluating an HIV seropositive person with headache, opportunistic infection or neoplasm should be included in the differential diagnosis. The clinical signs associated with these etiologies include: focal neurological signs; new seizure; depressed or altered mental status; headache that varies in quality or severity from prior headaches and headache lasting longer than three days (80, 38).

当评估一名HIV血清阳性患者的头痛时，机会性感染或肿瘤必须被包括在鉴别诊断中。和上述病因相关的临床表现包括：局灶性神经系统体征，新发的痫性发作，神志改变，头痛的性质和程度较前明显变化和头痛持续时间超过3天(80, 38)。

Differential diagnosis is primarily determined by the CD₄ count, as most opportunistic infections develop when CD₄ count drops below 200 cells/mm³. Despite the significant decrease in the incidence of OI since the introduction of HAART, the median CD₄ cell count of patients diagnosed with opportunistic infections has remained the same (72).

鉴别诊断首先要参考CD4计数，因为大部分机会性感染在CD4计数低于200 cells/mm³才出现。随着HAART的应用，机会性感染出现的概率显著下降，但是即使在治疗中的患者，CD4计数水平与机会性感染的相关性和以前比较并无明显变化(72)。

Not all patients with CNS opportunistic infection or neoplasm will report headache (Table 4). Headaches that accompany an opportunistic CNS infection or neoplasm are often associated with systemic symptoms or focal neurologic deficit (Table 7). Recognition of “red flags” that suggest a secondary headache should be recognized as heralding an underlying CNS process in people with and without HIV infection. For example, sudden onset headache or development of great intensity of pain over a short period of time should alert the medical care provider to the possibility of an intracranial abnormality such as an intracranial hemorrhage or a mass lesion. When headache is associated with signs of systemic illness such as fever, neck stiffness or a rash, an infection should be suspected, and further work-up should include blood tests and a lumbar puncture. Table 8 lists the clinical and radiologic features of disorders that may cause headache.

并不是所有的中枢神经系统机会性感染或肿瘤的患者都会伴有头痛(Table 4)。有机会性中枢神经系统感染和肿瘤的头痛患者多会有全身性症状或局灶神经系统功能损害(Table 7)。继发性头痛在HIV患者及非HIV患者中均有可能预示着潜在的中枢神经系统疾病在进展。比如，突发的头痛或短期内进行性加重的头痛可能提示颅内病变，如颅内出血或占位性病变。当头痛伴发全身症状，如发热、颈强或皮疹时，需怀疑有无感染可能，下一步的工作包括血液检测和腰椎穿刺检查。Table 8列举了可能致头痛疾病的临床和影像学特点。

The approach to evaluation of headache should be guided by the following factors: CD₄ count at the time of evaluation, presence or absence of fever, serologic status for T. gondii and C. neoformans, findings on neurologic examination, and medication list. Figure 1 suggests an approach to the evaluation of headache in an HIV seropositive person.

对头痛进行评估需要综合如下因素：CD4计数，有无发热，弓形体和新型隐球菌的血清学水平，神经科查体的发现和用药情况。图1提供了对HIV血清阳性人群头痛评估的思路。

A detailed history and careful neurological exam can guide further diagnostic evaluation. A convincing history of migraine as defined by IHS criteria, even after transformation to chronic daily headaches, may not require immediate neuroradiological or CSF evaluations if no focal neurological deficits are present (67).

详细的病史采集和仔细的神经科查体对下一步诊断评估意义重大。若有根据IHS标准确诊的偏头痛的确切病史，即使后面转化为慢性日间头痛，在没有局灶性神经系统缺损体征的情况下，可以不必立刻行神经影像学或脑脊液方面的检查 (67)。

Although an abnormal neurological examination is suggestive of intracranial pathology, headache characteristics are often not helpful; absence of fever, neck stiffness, and altered mental status are not as reliable in the HIV seropositive person (12).

头痛性质对诊断的帮助不大，但神经科查体异常对颅内病变会有一定的提示意义；HIV血清阳性患者的症状可能不可靠,如没有发热、颈强和精神状态改变(12)。

A clinical prediction rule has been tested for evaluating HIV seropositive people with headache to identify those in immediate need of imaging (38). Low risk was defined as having neither focal neurological findings, change in mental status or history of seizure and with a CD₄ count greater than 200 cells/mm³. Of the 35 subjects in this low risk group, none had abnormal findings on head CT.

一个临床评价标准已通过测试，可以协助判断哪些患者需立即行影像学检查(38)。无局灶神经系统症状及体征，无神志状态变化，无痫性发作，CD4计数大于200 cells/mm³，这些都被认为是低危因素。在低危组的35名个体中进行头颅CT检查，均无异常发现。

However, the CD₄ count needs to be interpreted with caution, especially if HAART therapy was recently initiated. If immune reconstitution inflammatory syndrome (see above) is suspected, the patient should be evaluated in the same way as someone with a CD₄ count less than 200 cells/mm³.

但是在接受HAART治疗刚开始不久时，CD4计数需要格外的注意。如果怀疑正处在免疫重建综合症期，那么这个病人需要像CD4计数小于200 cells/mm³的患者一样接受下一步评估。

The evaluation of headache in people with CD₄ counts greater than 200 cells/mm³ should be similar to that for people without HIV infection. If fever is present, lumbar puncture should be considered to evaluate for viral or bacterial meningitis. People with an absolute CD₄ count less than 200 cells/mm³ are at risk for developing toxoplasma encephalitis (TE), cryptococcal meningitis, or other opportunistic infection or neoplasm. If serum antigen to Cryptococcus neoformans (CrAg) is absent, cryptococcal meningitis is unlikely.

对于CD4计数高于200 cells/mm³的患者头痛的评估应与无HIV感染的人群相似。如果存在发热，那么有必要行腰穿检查以评估有无病毒性或细菌性脑膜炎。CD4绝对计数小于200 cells/mm³，有并发弓形体脑炎、隐球菌脑膜炎和其他机会性感染或肿瘤的风险。如果血清中新型隐球菌的抗原(CrAg)阴性，那么隐球菌脑膜炎的可能性极小。

A person without a focal neurologic deficit on neurologic examination is unlikely to have a CNS space-occupying lesion. If a focal deficit is present, the evaluation should include either a computerized tomography (CT) or magnetic resonance imaging (MRI) with and without administration of an intravenous contrast agent. Lesion location and contrast enhancement pattern can determine which infection or neoplasm is most likely (Table 8). If a solitary ring-enhancing mass lesion is present, lumbar puncture may be useful to differentiate between TE and primary CNS lymphoma (see Invasive Diagnostic Tests).

神经科查体无神经系统局灶性体征的个体患有中枢神经系统占位性病变的可能性很小。如果有局灶性体征，那么下一步的评估应包括CT或MRI，可以考虑增强。病变的部位和增强的结果对感染或肿瘤性质的确定具有帮助(Table 8)。如果是一个单发的环形强化的团块状病变，那么腰穿对区分是弓形体脑炎还是原发中枢神经系统淋巴瘤很有帮助（见有创性诊断）。

Neurosyphilis can occur at any stage of HIV infection and can cause headache. HIV seropositive people with new headache and a reactive rapid plasma reagin (RPR) or venereal diseases research laboratory (VDRL) test should undergo lumbar puncture to confirm or exclude the diagnosis of neurosyphilis.

神经梅毒可以在HIV感染的任一阶段出现并可导致头痛。新发头痛合并RPR或VDRL阳性的HIV血清阳性人群需要行腰穿检查以确定或排除神经梅毒的诊断。

The medical care provider should inquire about licit, illicit and over-the-counter medication usage (Table 5). The provider should also inquire about recent start, discontinuation or taper of medication.

需要询问合法的、非法的药物和非处方药品的使用情况(Table 5)，包括开始服用时间，停服时间或减量时间。

Lumbar Puncture: A lumbar puncture should be considered in any person presenting with new-onset headache in the setting of fever. Bacterial or viral meningitis may occur at any stage of HIV infection, and typically occurs in the setting of fever. If neurologic examination reveals a focal deficit, or the patient is obtunded or comatose, CT or MRI of the brain should be performed prior to lumbar puncture. If a space-occupying CNS lesion causes midline shift or is present in the posterior fossa, lumbar puncture should not be performed as it could result in CNS herniation. Cerebrospinal fluid tests should include cell count with differential, glucose, protein, bacterial culture and VDRL. Other tests that should be considered include: fungal cultures and antigen test for C. neoformans. If primary CNS lymphoma, PML, CMV or HSV encephalitis is suspected, polymerase chain reaction (PCR) assays for associated viral pathogens should be included. The sensitivity and specificity of most PCR assays are high (Table 9).

腰椎穿刺：新发头痛伴发热的任何患者都有必要行腰椎穿刺。细菌性或病毒性脑膜炎可出现在HIV感染的任何时期，多有发热。如果神经系统查体发现有局灶性功能缺陷，或病人反应迟钝或处于昏睡状态，那么头颅CT或MRI需先于腰穿检查。如果神经系统占位性病变致中线移位或者位于后颅窝，那么腰穿是禁忌的，因为有可能会导致脑疝。脑脊液检查需包括细胞分类、葡萄糖、蛋白、细菌培养和VDRL。其他可考虑的检查包括：真菌培养和新型隐球菌抗原检测。如果怀疑原发性中枢神经系统淋巴瘤、PML、CMV或HSV脑炎，那么需行相关病毒的病原PCR检查。大部分PCR检查的敏感性和特异性均很高(表 9)。

Brain Biopsy: Brain biopsy may be considered during the evaluation of solitary ring-enhancing CNS lesion. Although primary CNS lymphoma or TE are the most likely etiologies of such a lesion, the differential diagnosis also includes fungal or atypical bacterial abscess, cryptococcoma, syphilitic gumma, tuberculoma, and neoplasm other than primary CNS lymphoma (39). Several algorithms for the evaluation and treatment of CNS mass lesions in people with AIDS have been published (2, 5, 63). Brain biopsy typically involves a CT or MR guided stereotactic approach rather than open biopsy. Complications of brain biopsy vary from 0 to 7% and include hemorrhage, neurologic deficit, seizures, and rarely, infection or death (13, 54, 61, 93). Stereotactic brain biopsy performed on people with HIV infection provides a diagnosis in 88 to 98% of procedures and has a complication rate similar to the rate in people without HIV infection (19, 34, 39, 52).

脑活检： 单发的环状强化的中枢神经系统病变的进一步评估可考虑脑活检。虽然原发中枢神经系统淋巴瘤和弓形体脑炎是上述病变最常见的病因，但是鉴别诊断方面还包括真菌或非典型致病细菌所致的脓肿、隐球菌性肉芽肿、梅毒瘤、结核瘤和除了原发中枢神经系统淋巴瘤外的其它肿瘤(39)。有几个关于AIDS人群中枢神经系统占位病损评估和治疗的准则已经发表(2, 5, 63)。目前多是经CT或MR引导下立体定向行脑活检，少有开颅脑活检。脑活检的并发症报告为0-7%，包括出血、神经功能缺失、痫性发作和较少见的感染甚至死亡(13, 54, 61, 93)。对HIV患者行立体定向脑活检确诊率达88-98%，其并发症出现的概率与无HIV感染的人群基本相同(19, 34, 39, 52)。

Treatment of HIV-related headache should begin with evaluation of the patient. If a CNS lesion is not suspected or has been ruled out, therapy should be directed toward relieving discomfort. Many medications for treatment of headache are available. Table 10 lists some non-narcotic medications frequently used for treatment of headache. As the initial trial of a medication for reducing pain is often ineffective, several trials of different medications may be necessary to obtain relief. Maximum analgesic efficacy may not occur for several weeks after achieving the target dose, so each medication should be continued for at least two weeks at target dose prior to determining a medication is ineffective.

处理HIV相关性头痛首先应对患者进行评估。如果不太考虑或基本上除外中枢神经系统器质性病变，那么治疗的主要目的是减轻症状。许多治疗头痛的药物都可以使用。表 10列举了常用来治疗头痛的非阿片类药物。使用一种药物减轻疼痛的效果可能不明显，需要试用其他药物。药物有可能在达到目标剂量后的几周内才达到最大止痛效率，因此在决定一种药物无效前应至少需要持续目标剂量2周。

Choice of medication should be dictated by medication side effect profile and patient's past medical history and prior medication use. Most headache experts recommend a trial of at least two medications from each class of medication. Potential side effects of each medication should be discussed with the patient.

药物的选择应根据药物副作用、病人的既往史和药物使用史的情况而定。大多数头痛专家都建议每次至少试用同一类药物中的两种。每种药物潜在的副作用都需与患者讨论。

Some aspects of primary headache management may be different for HIV seropositive persons. For example, the threshold to treat chronic tension type headache with tricyclic antidepressants should be lower than in people without HIV infection. Frequently, analgesics will interact with antiretrovirals. Indomethacin, Tylenol and ASA can increase the toxicity of AZT (95). Patients with thrombocytopenia or coagulopathy should not be given ASA. The anticonvulsants carbamazepine and gabapentin interact with plasma levels of antiretroviral medications. In the same way, antiretroviral drugs may influence levels of pain medications, so serum drug levels need to be monitored closely.

HIV血清阳性患者的原发性头痛的处理在某些方面略有不同。用于治疗慢性紧张性头痛的三环类抗抑郁药的剂量应比无HIV感染者略低。通常止痛药会与抗逆转录病毒治疗相互作用。吲哚美辛、泰诺林和氨基水杨酸（ASA）可以增加AZT的毒性(95)。ASA在血小板减少或出凝血障碍的患者中是禁用的(95)。抗癫痫药如卡马西平和加巴喷丁会与血清中的抗逆转录病毒药物相互作用。同样，抗逆转录病毒药物会影响止痛药物的水平，所以血清的药物浓度水平需要密切监测。

Acute HIV infection often goes undiagnosed but early recognition is becoming more and more important because of the potential clinical benefit of early initiation of antiretroviral therapy. Symptoms usually present within days to weeks after initial exposure and include headache in 32-70% (53). Identification of subjects during this period requires a high index of clinical suspicion.

HIV的急性感染期经常漏诊。症状多在暴露后的数天至数周出现，其中包括在32-70%的个体中可出现头痛(53)。发现此期的患者需要在临床上提高警惕性。

Non-pharmacologic treatments for headache may also provide relief of headache discomfort. Such treatments include: neuroaugmentative techniques, such as transcutaneous electrical nerve stimulation (TENS); anesthetic techniques, such as nerve blocks; and complementary and alternative techniques, such as biofeedback, acupuncture and herbal remedies (46, 57, 69, 90).

非药物的治疗也可以减轻头痛。这些治疗包括：神经增强技术（neuroaugmentative techniques），如经皮神经电刺激(TENS)；麻醉技术，如神经阻滞；以及补充和替代治疗手段，如生物反馈、针灸和中草药治疗(46, 57, 69, 90)。

Patients who do not obtain relief from the treatments noted above, or patients with CNS mass lesions, may be candidates for narcotic analgesics. Although short-acting narcotics do provide relief of headache, prolonged use may cause rebound headache and addiction. If prolonged use of narcotics is anticipated, the medical provider should consider prescribing a long-acting narcotic, such as sustained release morphine or methadone, and refer the patient to a pain clinic.

对于经过上述治疗仍未缓解或具有中枢神经系统占位病变的患者，有可能下一步需要麻醉镇痛治疗。虽然短效麻醉药确实可以减轻头痛，但长期使用可能导致反弹性头痛和上瘾。如果预期会长期使用麻醉药物，医生可以考虑处方长效麻醉药，如缓释吗啡或美沙酮，并可建议病人去看疼痛门诊。

Headache is common in HIV-infected people. Evaluation of an HIV seropositive person should be guided by the CD₄ count and findings on neurologic examination. If an evaluation does not reveal an intracranial abnormality, pain should be managed with medications and other alternate therapies.

头痛在HIV感染的人群中很常见。对HIV血清阳性人群需根据CD4细胞的计数和神经科查体所见进行评估。如果评估未提示颅内异常，那么需要药物或其他治疗进行镇痛。

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