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45-Year-Old Woman With Recurrent Headache and Photophobia

2008; Elsevier BV; Volume: 83; Issue: 8 Linguagem: Inglês

10.4065/83.8.951

1942-5546

Farrah J. Mateen, David N. Mohr,

Infectious Diseases and Tuberculosis

A 45-year-old woman presented to the emergency department with headache and neck stiffness. Approximately 36 hours earlier, she had awoken with an unremitting, throbbing, generalized head pain, the severity of which she rated as 10 out of 10. It was exacerbated by neck movement, especially neck flexion, and accompanied by chills, photophobia, and nausea without vomiting. She denied fevers. The patient's medical history included diabetes mellitus, hypothyroidism, morbid obesity, dyslipidemia, gastroesophageal reflux disease, and chronic low back pain. She had had 4 previous episodes of diagnosed meningitis, treated 2, 8, 12, and 22 years previously; however, she could not recall the details of her hospitalizations and treatments, and records were not available. The patient had no residual deficits from the episodes, but she did recall that one of these episodes had been diagnosed as viral meningitis. She also reported chronic limitation of neck flexion for more than 2 decades and had previously been told that this was because she had extra ribs. The patient was taking aspirin, metformin, levothyroxine, esomeprazole, lovastatin, and calcium with vitamin D. She had no history of migraines. She denied antecedent trauma, contact with sick people, recent travel outside the country, and outdoor activities, such as camping. Nonetheless, the patient recalled pulling an embedded tick out of her skin 3 weeks before presentation. She had had no symptoms from this and recalled no rash. There were 2 dogs and a cat at her home. On examination, the patient was alert and oriented. Her heart rate was 70 beats/min (regular rhythm), blood pressure was 110/70 mm Hg while sitting, temperature was 36.1ϒC, and breath sounds were normal. Findings on abdominal examination were unremarkable. There was no rash or lymphadenopathy. She was intolerant of the room light but had no phonophobia. Speech was normal, and she was able to provide her own history. Cranial nerves II through XII, reflexes, tone, strength, sensation, findings on cerebellar examination, and gait were all within normal limits. 1.Which one of the following physical examination findings would be the most sensitive in the detection of meningeal irritation in this patient? a.Brudzinski signb.Kernig signc.Jolt accentuation of headached.Straight leg raisee.Babinski reflex Irritation of the meningeal layers surrounding the brain and spinal cord can lead to neck stiffness, or meningismus. Meningismus is rigidity with gentle forward flexion of the neck in a patient in the supine position. It can assist in narrowing the diagnosis of new-onset headache. Causes of meningismus can be either infectious (eg, inflammation related to purulent bacterial infection) or noninfectious (eg, blood from subarachnoid hemorrhage, tonsillar herniation), such that infectious meningitis cannot be presumed on the basis of meningismus alone. Meningismus has 70% sensitivity for detecting meningitis.1Attia J Hatala R Cook DJ Wong JG The rational clinical examination: does this adult patient have acute meningitis?.JAMA. 1999; 282: 175-181Crossref PubMed Scopus (211) Google Scholar Brudzinski sign (passive neck flexion resulting in compensatory hip and knee flexion) and Kernig sign (pain in the lower back or posterior thigh from extending the knee >135ϒ during hip flexion) are classic signs of meningeal irritation. Their reported sensitivities vary widely, from 5% to 97%,1Attia J Hatala R Cook DJ Wong JG The rational clinical examination: does this adult patient have acute meningitis?.JAMA. 1999; 282: 175-181Crossref PubMed Scopus (211) Google Scholar, 2Thomas KE Hasbun R Jekel J Quagliarello VJ The diagnostic accuracy of Kernig's sign, Brudzinski's sign, and nuchal rigidity in adults with suspected meningits.Clin Infect Dis. 2002 Jul 1; 35 (Epub 2002 Jun 5.): 46-52Crossref PubMed Scopus (192) Google Scholar and their specificities are generally considered to be high. However, 30% of the geriatric population, in whom spondylosis is common, have nuchal rigidity in the absence of meningitis, and 12% have a positive Kernig sign.3Puxty JAH Fox RA Horan MA The frequency of physical signs usually attributed to meningeal irritation in elderly patients.J Am Geriatr Soc. 1983; 31: 590-592PubMed Google Scholar The jolt accentuation of headache, although less commonly performed, has 97% sensitivity for meningitis4Uchihara T Tsukagoshi H Jolt accentuation of headache: the most sensitive sign of CSF pleocytosis.Headache. 1991; 31: 167-171Crossref PubMed Scopus (68) Google Scholar and would be the most sensitive for the detection of meningeal irritation. For this test, the patient is asked whether a headache is worsened by specific head movements. Findings on the test are considered positive when turning the head in the horizontal plane, at 2 to 3 rotations per second, worsens a preexisting headache. Unlike Kernig and Brudzinski signs, the jolt accentuation headache requires a patient to be conscious and alert. Straight leg raise has not been validated as a discriminatory test of meningeal symptoms. The Babinski reflex, which Babinski himself called the great toe sign, is a plantar extensor response to a noxious stimulus on the plantar surface of the foot.5Leon-S FE Prada LJ The true sign of Babinski [letter].Arch Pathol Lab Med. 2001; 125: 723PubMed Google Scholar It usually reflects upper motor neuron disease in adults and may be present in central nervous system conditions, such as stroke, brain tumor, or the postictal phase of a seizure. It is not a particularly useful physical sign when evaluating meningismus. In our patient, both Kernig and Brudzinski signs were found to be positive. Jolt accentuation of headache was not performed. There was a bilateral plantar flexor response. The patient was treated symptomatically for pain and nausea. 2.Which one of the following tests would be the most appropriate in evaluating this patient? a.Lumbar puncture (LP)b.Computed tomography (CT) of the headc.Magnetic resonance imaging (MRI) of the headd.Empiric antibiotic coveragee.Throat swab and culture This patient presented with an episode of meningismus and headache without fever. She had 2 of the 3 symptoms of the classic triad of meningitis. Only approximately 20% of patients with meningitis have all 3 symptoms of the triad.1Attia J Hatala R Cook DJ Wong JG The rational clinical examination: does this adult patient have acute meningitis?.JAMA. 1999; 282: 175-181Crossref PubMed Scopus (211) Google Scholar, 6Pizon AF Bonner MR Wang HE Kaplan RM Ten years of clinical experience with adult meningitis at an urban academic medical center.J Emerg Med. 2006; 30: 367-370Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar Because meningitis was strongly suspected in our patient, her case was treated as a life-threatening emergency. When meningitis is suspected, an LP is necessary to confirm or refute the diagnosis and should be performed immediately. Although it would be reasonable to perform any of the other listed tests, LP is a priority. Obtaining a blood culture at the same time as the LP is appropriate. The necessity of performing CT or MRI of the head before LP has been studied, and features of a well-performed history and physical examination point to whether head imaging is required before LP. Every clinician should consider that an occult brain mass or mass effect could be present and that removal of cerebrospinal fluid (CSF) could provoke cerebral herniation in certain circumstances. When a patient has a history of a stroke or mass lesion, new-onset seizures, an abnormal level of consciousness, papilledema, an immunocompromised state, or a focal deficit on neurologic examination, LP must be preceded by head imaging.7Hasbun R Abrahams J Jekel J Quagliarello VJ Computed tomography of the head before lumbar puncture in adults with suspected meningitis.N Engl J Med. 2001; 345: 1727-1733Crossref PubMed Scopus (354) Google Scholar Our patient lacked all of these characteristics. When head imaging is required but can be delayed, empiric antibiotics should be administered immediately after blood cultures have been obtained and before the patient is sent for CT or MRI. Throat swabs may identify specific organisms related to systemic infection, such as enteroviruses, but they will not discern whether a nervous system infection is present. Our patient declined an LP in the emergency department, so intravenous ceftriaxone, vancomycin, and acyclovir were started empirically. Findings on head CT were normal, as were those on basic laboratory tests, including a complete blood cell count and electrolyte panel, except for a mild leukocytosis (leukocyte count, 12.2 × 109/L [reference range, 3.5-10.5 × 109/L]). The patient was admitted to the hospital for observation and treatment. The next day, she agreed to an LP. She continued to have a headache and mild meningismus. 3.Given that an LP may cause a postprocedural headache, which one of the following is the best strategy for reducing the risk of a post-dural puncture headache in this patient? a.Instruct the patient to remain supine 30 minutes before the procedureb.Instruct the patient to remain supine 30 minutes after the procedurec.Perform the procedure with the patient sitting uprightd.Provide a one-time dose of sumatriptane.Use a fine 22-gauge needle Post-dural puncture headache is the most common complication of a diagnostic LP. Although 85% of post-dural puncture headaches resolve within 6 weeks, serious morbidity related to the post-dural puncture headache is possible.8Turnbull DK Shepherd DB Post-dural puncture headache: pathogenesis, prevention, and treatment.Br J Anaesth. 2003; 91: 718-729Crossref PubMed Scopus (570) Google Scholar Some headaches have been reported to last months and even years, and interventions used to treat such a post-dural puncture headache can result in death in rare circumstances.8Turnbull DK Shepherd DB Post-dural puncture headache: pathogenesis, prevention, and treatment.Br J Anaesth. 2003; 91: 718-729Crossref PubMed Scopus (570) Google Scholar Although no clinical evidence supports the usefulness of recumbency either before or after the procedure,9Hafer J Rupp D Wollbrück M Engel J Hempelmann G The effect of needle type and immobilization on postspinal headache [in German].Anaesthesist. 1997; 46: 860-866Crossref PubMed Scopus (38) Google Scholar patients often find that lying down is comfortable when having headache symptoms. The position in which the LP is performed (lateral decubitus vs sitting) has not been shown to affect the incidence of post-dural puncture headache. A randomized trial of sumatriptan in post-puncture headache showed no significant therapeutic benefit.10de las Heras-Rosas MA Rodriguez-Pérez A Ojeda-Betancor N Boralla-Rivera G Gallego-Alonso JI Failure of sumatriptan in post-dural puncture headache [in Spanish] [letter].Rev Esp Anestesiol Reanim. 1997; 44: 378-379PubMed Google Scholar The most important strategy one could take in this patient is to reduce the needle size. A balance must be achieved between using the smallest needle possible and allowing the operator to perform the study effectively without multiple attempts at penetrating the dura mater. With the introduction of smaller (22- and 24-gauge) needles in 1956, the incidence of post-puncture headache, which had been 66% in 1898, decreased to 11%.8Turnbull DK Shepherd DB Post-dural puncture headache: pathogenesis, prevention, and treatment.Br J Anaesth. 2003; 91: 718-729Crossref PubMed Scopus (570) Google Scholar Today, even smaller needles, such as the fine-gauge Whitacre and Sprotte pencil-point needles, can further reduce the incidence of post-dural puncture headache.8Turnbull DK Shepherd DB Post-dural puncture headache: pathogenesis, prevention, and treatment.Br J Anaesth. 2003; 91: 718-729Crossref PubMed Scopus (570) Google Scholar, 11Lavi R Yarnitsky D Rowe JM Weissman A Segal D Avivi I Standard vs atraumatic Whitacre needle for diagnostic lumbar puncture: a randomized trial.Neurology. 2007; 67: 1492-1494Crossref Scopus (95) Google Scholar An additional strategy to reduce the occurrence of a headache is to keep the angle of the needle perpendicular to the dura on puncture, theoretically creating a smaller puncture site. Our patient underwent an LP with a 22-gauge needle. She reported no worsening headache, back pain, or complications from the procedure. Findings on CSF analysis were as follows: glucose, 46 mg/dL (serum glucose, 95 mg/dL); protein, 135 mg/dL (reference range, 15-45 mg/dL); nucleated cells, 866 (92% lymphocytes); no xanthochromia; and negative results for cryptococcal antigen and West Nile virus IgG and IgM. Serology was negative for Lyme disease, and no growth was observed on cultures for bacteria and viruses. The patient's clinical picture was thought to be consistent with aseptic meningitis. 4.Which one of the following tests of the CSF would be most important in making a definite diagnosis in this patient? a.Culture for Streptococcus pneumoniaeb.Culture for Candida albicansc.Venereal Disease Research Laboratory (VDRL) testd.Cytology for malignant cellse.Herpes simplex virus (HSV) 2 polymerase chain reaction (PCR) A diagnosis of aseptic meningitis is made when no organism can be cultured. Viruses are the most common cause of aseptic meningitis and tend to be found with a lymphocyte-predominant pleocytosis (as seen in this patient). Given her previous episodes of meningitis, our patient was diagnosed as having recurrent aseptic meningitis, and the length of time during which her episodes occurred helped us make the final diagnosis. These episodes of meningitis left her with no lasting neurologic deficits and could, debatably, be called “benign.” Benign recurrent aseptic meningitis has a narrower differential diagnosis than that of acute meningitis. Bacterial meningitis may recur in immunocompromised patients, especially in patients with a history of head trauma or CSF leak, but tends not to be benign. It is more likely to present with hypoglycorrachia and an elevated total CSF protein content. Culture for C albicans would not be useful because it is not known to commonly cause recurrent benign meningitis. Although this patient has diabetes mellitus, she has no other evidence of an immunocompromised state, making invasive candidal disease unlikely. The Venereal Disease Research Laboratory test would not be useful because syphilis is unlikely to cause a recurrent acute neurologic process for this many years. Likewise, it would be unexpected for a malignancy to linger in the CSF for more than 20 years, although craniopharyngioma, cholesteatoma, and epidermoid tumor remain in the differential diagnosis.12Noseworthy JH 2nd ed. Neurological Therapeutics: Principles and Practice. Vol 2. Informa Healthcare, London, England2006Google Scholar Normal findings on an imaging study of the brain make these possibilities less likely. In our case, elevated CSF protein, normoglycorrachia, and lymphocyte predominance are in keeping with a diagnosis of viral meningitis. Herpes simplex virus 2 is thought to be the most common cause of recurrent aseptic meningitis, also known as Mollaret meningitis.13Mollaret P Meningite endothélio-leucocytaire multirécurrente bénigne: syndrome nouveau ou maladie nouvelle? Documents cliniques.Rev Neurol. 1944; 76: 57-76Google Scholar Other possibilities for a benign recurrent aseptic meningitis include drug hypersensitivity to repeated administration of a medication, systemic lupus erythematosus, Behçet disease, and Vogt-Koyanagi-Harada syndrome.12Noseworthy JH 2nd ed. Neurological Therapeutics: Principles and Practice. Vol 2. Informa Healthcare, London, England2006Google Scholar Our patient had no laboratory or clinical features of systemic lupus erythematosus. Behçet disease typically involves recurrent genital and mouth ulcers and uveitis, which our patient did not have. Although Behçet disease can be episodic and CSF pleocytosis can occur, a variety of skin manifestations would usually also be present.14Kidd D Steuer A Denman AM Rudge P Neurological complications in Behçet's syndrome.Brain. 1999; 122: 2183-2194Crossref PubMed Scopus (287) Google Scholar Similarly, Vogt-Koyanagi-Harada syndrome tends to have accompanying features of alopecia, vitiligo, and auditory dysfunction; although CSF pleocytosis, fever, and focal neurologic signs may occur, funduscopic changes from depigmentation of the choroid would be expected.15Andreoli CM Foster CS Vogt-Koyanagi-Harada disease.Int Ophthalmol Clin. 2006; 46: 111-122Crossref PubMed Scopus (67) Google Scholar Polymerase chain reaction studies for HSV-1 and HSV-2 were sent for testing. The patient continued to have a dull headache and neck discomfort. 5.5. Which one of the patient's medications would be most likely associated with aseptic meningitis? a.Aspirinb.Lovastatinc.Calcium with vitamin Dd.Levothyroxinee.Esomeprazole Medications can be important offending agents in aseptic meningitis, especially in cases of repeated meningitic episodes. Discontinuation of the offending medication can lead to symptomatic resolution. Among the most common medications to cause aseptic meningitis are nonsteroidal anti-inflammatory drugs, carbamazepine, isoniazid, and trimethoprim-sulfamethoxazole.12Noseworthy JH 2nd ed. Neurological Therapeutics: Principles and Practice. Vol 2. Informa Healthcare, London, England2006Google Scholar The only commonly implicated medication that our patient was taking was a nonsteroidal anti-inflammatory medication (aspirin). Because she had no history of cardiovascular or cerebrovascular disease, aspirin was discontinued temporarily. Lovastatin, calcium with vitamin D, levothyroxine, and esomeprazole are not known to be associated with repeated episodes of meningitis. Findings on PCR for HSV-2 were positive. The patient was diagnosed as having HSV-2-related meningitis on the basis of the findings on CSF analysis; her history of benign, recurrent episodes of meningitis; and her lack of neurologic deficits on examination. Acyclovir was changed to oral valacyclovir, and other antibiotics were discontinued. All cultures were negative for growth, and her symptoms resolved before discharge from the hospital. After discharge, she was lost to follow-up. Meningitis is common and potentially fatal. Bacterial meningitis occurs at a rate of 5 to 10 cases per 100,000 person-years in the United States, amounting to 25,000 cases annually.12Noseworthy JH 2nd ed. Neurological Therapeutics: Principles and Practice. Vol 2. Informa Healthcare, London, England2006Google Scholar Viral meningitis is thought to occur less commonly, but initial discrimination between bacterial and viral meningitis can be difficult. Prompt recognition and treatment, including urgent provision of appropriate antibiotic therapy, saves lives. Viral meningitis is classically marked by a syndrome of headache, fever (temperature, 38ϒC-40ϒC), meningismus, and photophobia, with an accompanying CSF pleocytosis. Cerebrospinal fluid glucose levels tend to be normal to slightly low, and CSF protein concentrations tend to be normal to mildly elevated. Enteroviruses (eg, coxsackievirus, echovirus) are the most common cause of viral meningitis, but arboviruses (eg, West Nile virus, St Louis encephalitis virus), herpesviruses (eg, human herpesvirus 6, varicella zoster virus), human immunodeficiency virus, mumps virus, and lymphocytic choriomeningitis virus should all be considered.12Noseworthy JH 2nd ed. Neurological Therapeutics: Principles and Practice. Vol 2. Informa Healthcare, London, England2006Google Scholar Because viruses may not be easily identified on CSF studies, they remain the most common cause of aseptic meningitis. Mollaret,13Mollaret P Meningite endothélio-leucocytaire multirécurrente bénigne: syndrome nouveau ou maladie nouvelle? Documents cliniques.Rev Neurol. 1944; 76: 57-76Google Scholar a French physician, first described recurrent benign aseptic meningitis in 1944, noting that this syndrome was marked by self-limited episodes of headache, CSF protein elevation, and lymphocytic pleocytosis. Cases reported since that time show no residual neurologic deficits due to these meningitic episodes and demonstrate that attacks can be separated by symptom-free intervals of weeks, months, or even years.16Steel JG Dix RD Baringer JR Isolation of herpes simplex virus type 1 in recurrent (Mollaret) meningitis.Ann Neurol. 1982; 11: 17-21Crossref PubMed Scopus (68) Google Scholar Mollaret cells, which can be identified microscopically and are likely monocytic in origin, are not specific to Mollaret meningitis, appear only transiently because of their fragility, and are rarely investigated.17Stoppe G Stark E Patzold U Mollaret's meningits: CSF-immunocytological examinations.J Neurol. 1987; 234: 103-106Crossref PubMed Scopus (25) Google Scholar Until the advent of PCR, Mollaret meningitis was considered rare or uncommon, and no infectious etiology could be identified. Recently, however, HSV-116Steel JG Dix RD Baringer JR Isolation of herpes simplex virus type 1 in recurrent (Mollaret) meningitis.Ann Neurol. 1982; 11: 17-21Crossref PubMed Scopus (68) Google Scholar and especially HSV-218Cohen BA Rowley AH Long CM Herpes simplex type 2 in a patient with Mollaret's meningitis: demonstration by polymerase chain reaction.Ann Neurol. 1994; 35: 112-116Crossref PubMed Scopus (58) Google Scholar have been identified consistently. Patients with Mollaret meningitis do not necessarily have a recognized history of HSV infection, nor in most cases do they have oral and/or herpetic lesions or a history thereof. One retrospective case series found that only 24% of people with Mollaret meningitis had a history of HSV genital infection at any point.19Tedder DG Ashley R Tyler KL Levin MJ Herpes simplex virus infection as a cause of benign recurrent lympohcytic meingitis.Ann Intern Med. 1994; 121: 334-338Crossref PubMed Scopus (170) Google Scholar The diagnosis of Mollaret meningitis portends an excellent prognosis,17Stoppe G Stark E Patzold U Mollaret's meningits: CSF-immunocytological examinations.J Neurol. 1987; 234: 103-106Crossref PubMed Scopus (25) Google Scholar with long symptom-free intervals and no lasting deficits. Episodes of meningitis tend to recur, as in our patient, but usually last for only a few days. Cases with focal neurologic deficits, seizures, and coma have been reported with periodic meningitides before HSV identification. Whether these cases were caused by HSV-2 or a different etiology is difficult to ascertain. The treatment of Mollaret meningitis is uncertain and has not been studied in a randomized controlled trial. Acyclovir may limit the natural course of symptoms20Bergström T Alestig K Treatment of primary and recurrent herpes simplex virus type 2 induced meningitis with acyclovir.Scand J Infect Dis. 1990; 22: 239-240Crossref PubMed Scopus (49) Google Scholar; however, attacks usually resolve spontaneously, with or without antiviral treatment. Seizure prophylaxis has not been recommended. After a course of intravenous acyclovir, our patient's symptoms completely resolved. Correct answers: 1. c, 2. a, 3. e, 4. e, 5. a