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Editorials

A Careful Neurologic Examination Should Precede Neuroimaging Studies in

HIV-Infected Patients with Headache

Headache is a common symptom in patients withHIV infection. It is the most common form of pain,

more common than painful peripheral neuropathy,and has been reported as the presenting manifes-tation of AIDS in 12.5% to more than 55% of pa-tients (1). Headaches in HIV-infected patients maybe caused by HIV-associated aseptic meningitis,antiretroviral and other therapies, or opportunisticinfections and neoplasms arising in the face of im-paired cellular immunity. Causes of the latter arelegion and include opportunistic infections such asCNS toxoplasmosis, cryptococcal meningitis, pri-mary central nervous system lymphoma, and lym-phomatous meningitis. Sinusitis is common withadvanced HIV immunosuppression and is also apotential cause of headaches. The frequency withwhich significant disease is determined to be thecause of headache in this population is highly de-pendent on the nature of the population studied. Forinstance, Goldstein found serious underlying dis-ease in 40 (82%) of 49 patients in a study of hos-pitalized patients (2), whereas Singer found that in-tracranial opportunistic infection or tumor waspresent in only 4% of HIV-infected patients pre-senting as outpatients (3). Nevertheless, the vastmajority of headaches in HIV-infected patients areno different from headaches in a control HIV-un-

infected population (l). These headaches bear norelation to CD4 T-lymphocyte counts, cerebrospi-nal fluid parameters, cranial MR imaging abnor-malities, the presence of sinusitis, or the use of zi-dovudine (1). They have been associated withpolypharmacy, depression, anxiety, and insomnia,and are often relatively unresponsive to conven-tional headache therapies (4). Multiple causes ofheadaches may be observed in a single patient.

When confronted by an HIV-infected patientcomplaining of headache, the treating physicianschief concern is the presence of a life-threatening,

treatable illness. Does the patient have an intracra-nial mass lesion or meningitis? Unfortunately, noconsensus has evolved regarding the best diagnos-tic approach for the evaluation of the HIV-infectedperson presenting with headache. The absence offever, neck stiffness, and altered mental status hasbeen suggested as effectively eliminating the pos-sibility of meningitis, but whether this remains truein the HIV-infected population is open to question.Neurologists with experience in treating patientswith AIDS recognize the importance of CD4 cellcounts in their approach to management of theHIV-infected patient with headache. Generally, inthe absence of significant immunosuppression, CTor MR imaging is not suggested unless focal find-ings are present on neurologic examination.

The findings in the study by Graham and col-leagues (page 451) are not unexpected; their pop-

ulation was screened in advance. Allegedly, nonehad altered mental status, meningeal signs, neuro-logic findings, or the worst headache of theirlife. In their HIV-seropositive population withoutsignificant immunosuppression, defined as havinga CD4 cell count 200 cells/cu mm, no abnormalfindings on unenhanced and contrast-enhanced cra-nial CT scans were noted. Even in the group withCD4 cell counts 200 cells/cu mm, only 14(15.7%) of 89 had mass lesions and another 4(4.5%) had white matter lesions. This is not unlikeobservations found with CSF analysis in whichCD4 cell counts 200 cells/cu mm militate againstthe likelihood of finding opportunistic infection.Although it is clear that the risk of opportunisticCNS infections greatly increases when CD4 cellcounts drop below 200 cells/cu mm, these infec-tions certainly occur in patients with higher cellcounts. Approximately 10% of AIDS patients withcerebral toxoplasmosis or progressive multifocalleukoencephalopathy (PML) have CD4 cell counts200 cells/cu mm.

Importantly, Graham and colleagues do not ad-dress the quality and thoroughness of the neurolog-ic examinations performed. Surely there is a dif-

ference between the hurried house officersexamination in an emergency room and the refinedexamination performed by an experienced neurol-ogist for probing the characteristics of a headacheand eliciting subtle focal neurologic abnormalities.This is an essential point. How many of the 14patients with intracranial mass lesions would haveexhibited absent spontaneous venous pulsations onfunduscopy, a subtle upper extremity drift, limb in-coordination, increased tone, or sensory loss had aneurologist performed the examination? A carefulhistory is equally important. A convincing history

of migraine or cluster headaches, even in the faceof severe immunosuppression, militates stronglyagainst opportunistic infection or space-occupyinglesions (4). Similarly, chronic daily headaches, de-fined as daily and near-daily headaches lasting formore than 4 hours per day for more than 15 daysper month for more than 1 month, argues againstunderlying identifiable intracranial disease, partic-ularly in the absence of abnormalities on neurolog-ic examination (4). A neurologic consultation ismore cost-effective than either a CT scan or an MRexamination. Additionally, other neurologic com-plications of HIV infection, such as early cognitiveimpairment, peripheral neuropathy, or myelopathy,may be recognized, whereas they easily may beoverlooked without careful neurologic examina-

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tion. While obtaining a CD4 cell count is certainlyworthwhile, as the authors suggest, for patients onantiretroviral therapies, this result is generallyavailable from outpatient studies proximate to thetime of the patients presentation with headache.CD4 cell counts are not inexpensive nor is a testperformed in an urgent fashionfacts providinganother argument for a formal neurologic consul-

tation when evaluating the HIV-infected patientwith headache.

The presence of mass lesions or meningeal en-hancement (not observed among the patients in thisstudy) is the major concern. Cerebral atrophy andwhite matter lesions as described by the authors arenot particularly relevant when addressing the issueof headaches. Although both may be features ofHIV dementia, HIV dementia does not appear tobe a cause of headache. The authors present insuf-ficient data to determine whether the white matterlesions seen were the consequence of PML, which

may on occasion be associated with headache.Headache in isolation, ie, without focal neurologicabnormalities, however, would be highly unusualfor PML.

Graham and colleagues have demonstrated a re-lationship between significant immunosuppression(CD4 cell count 200 cells/cu mm) and the pres-

ence of intracranial abnormalities at the time of CTscan. They demonstrate that even in the immuno-suppressed population, clinically relevant lesionsremain relatively rare. Many questions remain re-garding the best approach to the evaluation of thesepatients; however, the value of a thorough and pre-cise neurologic examination in the evaluation ofthese patients cannot be underestimated.

JOSEPH R BERGER, M.D.AVINDRA NATH, M.D.

Department of NeurologyUniversity of Kentucky College of Medicine

Lexington, KY

References

1. Berger JR, Stein N, Pall L. Headache and human immunode-

ficiency virus infection: a case control study. Eur Neurol 1996;36:229233

2. Goldstein J. Headache and acquired immunodeficiency syn-drome. Neurol Clin 1990;8:947960

3. Singer EJ, Kim J, Fahy-Chandon B, Datt A, Tourtellotte WW.Headache in ambulatory HIV-1-infected men enrolled in a lon-gitudinal study. Neurology 1996;47:487494

4. Mirsattari S, Power C, Nath A. Primary headaches in HIV-in-fected patients. Headache 1999;39:310

Funded Research and Neuroradiology

Research grants . . . are the most widely-acceptedmeasure of productivity. . . . [They] recognize pastcontributions as well as good ideas and plans for fu-ture work. The process of writing a fundable researchproposal is a major creative undertaking and it is rec-ognized as such by peers. Research grant dollars area measure of research value, because the value of theproduct is equal to its cost of production.

Karl Lanks (1)

Funded research has value for the individual in-vestigator, for the radiology department and the in-stitution, for our profession, and ultimately for our

patients. For some of us, having an external sourceof support is the only way research can be con-ducted. Grant funding buys the investigator timeaway from clinical duties. Funding provides sup-plies and statistical support, and it pays the rent forthe imaging instrument on which the experiment isto be performed. External funding is highly valuedby the administrators at an institution, and obtain-ing it distinguishes an investigator from other fac-ulty. In fact, it often results in fast-track promotionand appointment to important institutional commit-tees. Radiology committees are liberally sprinkled

with individuals who believe extramural funding isan essential attribute in a candidate for departmentchair. It is their desire that, under the new chair,the radiology department will improve. Many be-lieve that one cannot effectively promote researchunless one has been there and knows first-hand

the effort and sacrifice that must be expended tocompete successfully for extramural funding. Atanother level, in the selection process for membersof NIH initial review groups, study sections, ad-ministrators endeavor to choose individuals whoare currently funded.

There is subtle, but real, disapproval by our moreclinically oriented colleagues of the contributionsof individuals spending more of their time on re-search. This resentment is perceived by trainees(2). It is crucial for a chairman to establish an en-vironment in which the effort of investigators isrecognized as important for the prestige of the de-partment nationally and internationally. Funded re-search is critical for the very survival of an aca-demic department. Individuals with the power todismember radiology value extramural funding; itbrings in considerable indirect support, which thedean can use at his/her discretion, and which canamount to 40% to 100% of the direct costs of per-forming the project. An accelerating number ofawards enhances the reputation of the university.Consequently, this factor is germane to the equa-tion when issues of turf are discussed. Among thethree missions of a medical centerteaching, pa-tient care, and researchonly the last can be ob-

jectively quantified. The annual tabulation of re-search funding by federal government agencies(NIH, National Science Foundation, Departments

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of Energy and Defense, etc.) is closely watched byinstitutional administrators. The institutions classrank is on display. In fiscal year 1998, there were1509 active grants classified as imaging in theNIH extramural program (3). In this enterprise, ra-diologists play a minor role. For the 1997 fiscalyear, 59 MDs or MD/PhDs in radiology depart-ments were Principal Investigators (PIs) on NIH

grants. In the 1998 fiscal year, the number rose to87. One hundred ninety-eight of these imaginggrants are sponsored by the National Institute ofNeurological Diseases and Stroke (3). Many moreimaging grants concerned with the central nervoussystem have been awarded by the National CancerInstitute (NCI) and the institutes on aging (NIA),drug abuse (NIDA), alcohol abuse (NIAAA), re-search resources (NCRR), and human development(NICHD). Twelve members of the American So-ciety of Neuroradiology are PIs on NIH-fundedprojects. By any standard, this performance is dis-

mal, and it reflects a singular lack of focused re-search effort by our profession.With the advent of MR imaging, fortune provid-

ed us with a powerful analytical instrument capableof investigating certain physiologic processes in thebrain in vivo. The significance of this developmenthas not been lost on neuroscientists from other dis-ciplines. I believe it is unethical to withhold theuse of a medical instrument from a researcherwhose goal is to investigate a hypothesis that mayreduce patient suffering. Provided that time isavailable on the instrument and the investigator is

prepared to pay for this time, the instrument shouldnot be withheld purely on the basis of turf is-sues. Neuroradiologists should be eager to collab-orate with scientists from other disciplines whowish to initiate an investigation using MR imaging.Often they will come to us first with their ideas.By being helpful initially, we almost can assureourselves a role in the project; otherwise, they maybypass us and ultimately co-opt the imaging sci-entists in our own department. We in neuroradiol-ogy should be prepared to collaborate enthusiasti-cally with others by lending the project the benefit

of our unique insight. Having said that, it is alsoof critical importance that we assume equal footingin our particular research communities by acquisi-tion of research funding as PIs.

The field of medicine is in an unsettled state.Practice patterns are being altered by governmentpolicy and business decisions imposed by hospitalsand insurance companies. Unit reimbursement for

our skills is shrinking. We are being monitored toverify that, as faculty, we actually are involved inthe performance of procedures that senior residentsand fellows once managed as an important stepalong their training pathway. As a group, our re-sponse to these challenges has been to work harder,to interpret more studies, and to spend less time inintellectual and research pursuits.

Although the situation in medicine can be de-scribed as somewhat chaotic, in chaos there is op-portunity. A singular opportunity exists over thenext decade because of the recently passed Senateversion of the Federal Research Investment Act,which calls for doubling federal civilian researchsupport by the year 2010. It is said that $1.00 instart-up funds is needed for every $3.00 of ultimategrant support. I am not so optimistic. I believe that,after factoring in the capital expenditures associ-ated with the instruments we use and the time lostfrom clinical activities, department expendituresmust be closer to $2.00 for every $3.00 ultimatelysecured through grant funding. Departments thatare running from hand-to-mouth on current clinicalrevenue will not have the resources to compete suc-cessfully for funding in this environment. My pre-diction is that the well-endowed departments, thosewith significant institutional support or reserve de-partmental funds, will benefit. The ranking of ra-diology departments will change in the next fewyears, in some instances dramatically, and thosewith inspired leadership will find it possible toleapfrog over a number of other establishedinstitutions.

By exhibiting initiative in the arena of funded re-search, neuroradiologists can directly influence thechanges that will inevitably affect our profession.

DIXON M. MOODYProfessor and Chief of Neuroradiology

Wake Forest University School of MedicineWinston-Salem, NC

References

1. Lanks, KW. Academic Environment. A Handbook for EvaluatingFaculty Employment Opportunities.Brooklyn, NY: Faculty Press;1990

2. Hillman BJ, Putman CE. Fostering research by radiologists.Recommendations of the 1991 summit meeting. Invest Radiol1992;27:107110

3. http://grants.nih.gov/grants/bioimaging/nihbioimagingawards1998.htm