The International Classification of Headache Disorders 2nd Edition



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9. Headache attributed to infection


9.1 Headache attributed to intracranial infection

9.1.1 Headache attributed to bacterial meningitis

9.1.2 Headache attributed to lymphocytic meningitis

9.1.3 Headache attributed to encephalitis

9.1.4 Headache attributed to brain abscess

9.1.5 Headache attributed to subdural empyema

9.2 Headache attributed to systemic infection

9.2.1 Headache attributed to systemic bacterial infection

9.2.2 Headache attributed to systemic viral infection

9.2.3 Headache attributed to other systemic infection

9.3 Headache attributed to HIV/AIDS

9.4 Chronic post-infection headache

9.4.1 Chronic post-bacterial meningitis headache

Coded elsewhere:

Headache disorders attributed to extracranial infections of the head (such as ear, eye and sinus infections) are coded as subtypes of 11. Headache or facial pain attributed to disorder of cranium, neck, eyes, ears, nose, sinuses, teeth, mouth or other facial or cranial structures.

General comment

Primary or secondary headache or both?

When a new headache occurs for the first time in close temporal relation to an infection, it is coded as a secondary headache attributed to the infection. This is also true if the headache has the characteristics of migraine, tension-type headache or cluster headache. When a pre-existing primary headache is made worse in close temporal relation to an infection, there are two possibilities, and judgment is required. The patient can either be given only the diagnosis of the pre-existing primary headache or be given both this diagnosis and the diagnosis of headache attributed to the infection. Factors that support adding the latter diagnosis are: a very close temporal relation to the infection, a marked worsening of the pre-existing headache, very good evidence that the infection can aggravate the primary headache and, finally, improvement or resolution of the headache after relief from the infection.
Definite, probable or chronic?

A diagnosis of Headache attributed to an infection usually becomes definite only when the headache resolves or greatly improves after effective treatment or spontaneous remission of the infection. If the infection cannot be treated effectively or does not remit spontaneously, or when there has been insufficient time for this to happen, a diagnosis of Headache probably attributed to infection is usually applied.

This is not the case for 9.1.1 Headache attributed to bacterial meningitis. It is recognised that this headache may become chronic. When the causative infection is effectively treated or remits spontaneously but headache persists after 3 months, the diagnosis changes to 9.4.1 Chronic post-bacterial meningitis headache.

In other cases when the infection is eliminated but headache does not resolve or markedly improve after 3 months, a diagnosis of A9.4.2 Chronic post-non-bacterial infection headache may be considered. This is described only in the appendix as such headaches have been poorly documented, and research is needed to establish better criteria for causation.

Introduction


Headache is a common accompaniment of systemic viral infections such as influenza. It is also common with sepsis; more rarely it may accompany other systemic infections.

In intracranial infections headache is usually the first and the most frequently encountered symptom. Occurrence of a new type of headache which is diffuse, pulsating and associated with a general feeling of illness and/or fever should direct attention towards an intracranial infection even in the absence of a stiff neck. Unfortunately, there are no good prospective studies of the headaches associated with intracranial infection and precise diagnostic criteria for these subtypes of headache cannot be developed in all cases.


9.1 Headache attributed to intracranial infection

9.1.1 Headache attributed to bacterial meningitis

Diagnostic criteria:

A. Headache with at least one of the following characteristics and fulfilling criteria C and D:

1. diffuse pain

2. intensity increasing to severe

3. associated with nausea, photophobia and/or phonophobia

B. Evidence of bacterial meningitis from examination of CSF

C. Headache develops during the meningitis

D. One or other of the following:

1. headache resolves within 3 months after relief from meningitis

2. headache persists but 3 months have not yet passed since relief from meningitis

Comments:

Headache is the commonest and may be the first symptom of bacterial meningitis. Headache is a key symptom of meningeal syndrome or meningism consisting usually of headache, neck stiffness and photophobia.

A variety of microorganisms may cause primary or secondary meningitis. Direct stimulation of the sensory terminals located in the meninges by bacterial infection causes the onset of headache. Bacterial products (toxins), mediators of inflammation such as bradykinin, prostaglandins and cytokines and other agents released by inflammation not only directly cause pain but also induce pain sensitisation and neuropeptide release.

When headache persists after 3 months, code as 9.4.1 Chronic post-bacterial meningitis headache.

9.1.2 Headache attributed to lymphocytic meningitis

Diagnostic criteria:

  1. Headache with at least one of the following characteristics and fulfilling criteria C and D:

1. acute onset

2. severe intensity

3. associated with nuchal rigidity, fever, nausea, photophobia and/or phonophobia

B. Examination of CSF shows lymphocytic pleocytosis, mildly elevated protein and normal glucose1

C. Headache develops in close temporal association to meningitis

D. Headache resolves within 3 months2 after successful treatment or spontaneous remission of infection



Notes:

1. Virus, borrelia, listeria, fungus, tuberculosis or other infective agent(s) may be identified by appropriate methods.

2. Headache usually resolves within 1 week.


Comments:

Headache, fever, photophobia and nuchal rigidity are the main symptoms of lymphocytic or non-bacterial meningitis and headache may remain as the main symptom throughout the course of the disease.

Headache can appear with intracranial infection but also in systemic inflammation. Since the signs of systemic inflammation associated with headache do not necessarily mean meningitis or encephalitis, diagnosis of lymphocytic meningitis must be confirmed by CSF examination.

Enteroviruses account for most viral causes. Herpes simplex, adenovirus, mumps and others may also be responsible.

9.1.3 Headache attributed to encephalitis

Diagnostic criteria:

  1. Headache with at least one of the following characteristics and fulfilling criteria C and D:

1. diffuse pain

2. intensity increasing to severe

3. associated with nausea, photophobia or phonophobia


  1. Neurological symptoms and signs of acute encephalitis, and diagnosis confirmed by EEG, CSF examination, neuroimaging and/or other laboratory investigations1

  2. Headache develops during encephalitis

  3. Headache resolves within 3 months after successful treatment or spontaneous remission of the infection



Note:

1. PCR method gives the specific diagnosis.
Comments:

The causes of headache include both meningeal irritation and increased intracranial pressure. Head pain may also be a systemic reaction to the toxic products of the infecting agent(s). Headache may occur early and be the only clinical symptom of encephalitis.

Herpes simplex virus, arbovirus and mumps are known causes of encephalitis. Except for HSV encephalitis (in which 95% of cases are identifiable with PCR), the causative virus is identified in fewer than half of cases of encephalitis.


9.1.4 Headache attributed to brain abscess

Diagnostic criteria:

  1. Headache with at least one of the following characteristics and fulfilling criteria C and D:

1. bilateral

2. constant pain

3. intensity gradually increasing to moderate or severe

4. aggravated by straining

5. accompanied by nausea


  1. Neuroimaging and/or laboratory evidence of brain abscess

  2. Headache develops during active infection

  3. Headache resolves within 3 months after successful treatment of the abscess



Comments:

Direct compression and irritation of the meningeal or arterial structures and increased intracranial pressure are the mechanisms for causing headache.

The most common organisms causing brain abscess include streptococcus, staphylococcus aureus, bacteroides species and enterobacter. Predisposing factors include infections of paranasal sinuses, ears, jaws, teeth or lungs.


9.1.5 Headache attributed to subdural empyema

Diagnostic criteria:

  1. Headache with at least one of the following characteristics and fulfilling criteria C and D:

1. unilateral or much more intense on one side

2. associated with tenderness of the skull

3. accompanied by fever

4. accompanied by stiffness of the neck



  1. Neuroimaging and/or laboratory evidence of subdural empyema

  2. Headache develops during active infection and is localised to or maximal at the site of the empyema

  3. Headache resolves within 3 months after successful treatment of the empyema



Comments:

Headache is caused by meningeal irritation, increased intracranial pressure and/or fever.

Subdural empyema is often secondary to sinusitis or otitis media. It may also be a complication of meningitis. Early diagnosis is best made by CT or MRI.


9.2 Headache attributed to systemic infection

Coded elsewhere:

Headache attributed to meningitis or encephalitis accompanying systemic infection should be coded accordingly under 9.1 Headache attributed to intracranial infection.
Diagnostic criteria:

  1. Headache with at least one of the following characteristics and fulfilling criteria C and D:

1. diffuse pain

2. intensity increasing to moderate or severe

3. associated with fever, general malaise or other symptoms of systemic infection


  1. Evidence of systemic infection

  2. Headache develops during the systemic infection

  3. Headache resolves within 72 hours after effective treatment of the infection



Comments:

Headache in systemic infections is usually a relatively inconspicuous symptom and diagnostically unhelpful. These conditions are mostly dominated by fever, general malaise and systemic symptoms. Nevertheless, some systemic infections, particularly influenza, have headache as a prominent symptom along with fever and other symptoms. In other cases, systemic infection is accompanied by meningitis or encephalitis, and the headache should be coded to these disorders.

The great variability in their propensity for causing headache indicates that systemic infections do not have this effect simply through fever. The mechanisms causing headache include direct effects of the microorganisms themselves. In infectious disease, headache commonly coexists with fever and may be dependent on it, but headache can occur in the absence of fever. The presence or absence of fever may be used in the differential classification of headache. The exact cause of headache by fever is not elucidated. Some infective microorganisms may influence brainstem nuclei which release substances to cause headache, or endotoxins may activate inducible NOS causing production of nitric oxide (NO). The exact nature of these mechanisms remains to be investigated.


9.2.1 Headache attributed to systemic bacterial infection

Diagnostic criteria:

  1. Headache fulfilling criteria for 9.2 Headache attributed to systemic infection

  2. Laboratory investigation discloses the inflammatory reaction and identifies the organism



Comment:

Some infective agents have a particular tropism for the central nervous system. They may activate brainstem nuclei where release of toxins induces headache mechanisms.

9.2.2 Headache attributed to systemic viral infection

Diagnostic criteria:

  1. Headache fulfilling criteria for 9.2 Headache attributed to systemic infection

  2. Clinical and laboratory (serology and/or PCR molecular) diagnosis of viral infection



9.2.3 Headache attributed to other systemic infection

Diagnostic criteria:

  1. Headache fulfilling criteria for 9.2 Headache attributed to systemic infection

  2. Clinical and laboratory (serology, microscopy, culture or PCR molecular) diagnosis of infection other than bacterial or viral



9.3 Headache attributed to HIV/AIDS

Coded elsewhere:

Headache attributed to a specific supervening infection is coded according to that infection.
Diagnostic criteria:

  1. Headache with variable mode of onset, site and intensity1 fulfilling criteria C and D

  2. Confirmation of HIV infection and/or of the diagnosis of AIDS, and of the presence of HIV/AIDS-related pathophysiology likely to cause headache2, by neuroimaging, CSF examination, EEG and laboratory investigations

  3. Headache develops in close temporal relation to the HIV/AIDS-related pathophysiology

  4. Headache resolves within 3 months after the infection subsides



Notes:

1. Headache as a symptom of HIV infection is dull and bilateral. Otherwise. the onset, site and intensity of headache vary according to the HIV/AIDS-related conditions (such as meningitis, encephalitis or systemic infection) that are present.

2. See Comments.


Comments:

Dull bilateral headache may be a part of the symptomatology of HIV infection. Headache may also be attributed to aseptic meningitis during HIV infection (but not exclusively in the AIDS stages) and to secondary meningitis or encephalitis associated with opportunistic infections or neoplasms (which mostly occur in the AIDS stages). The most common intracranial infections in HIV/AIDS are toxoplasmosis and cryptococcal meningitis.

Headache occurring in patients with HIV/AIDS but attributed to a specific supervening infection is coded to that infection.


9.4 Chronic post-infection headache

9.4.1 Chronic post-bacterial meningitis headache

Diagnostic criteria:

  1. Headache with at least one of the following characteristics and fulfilling criteria C and D:

1. diffuse continuous pain

2. associated with dizziness

3. associated with difficulty in concentrating and/or loss of memory


  1. Evidence of previous intracranial bacterial infection from CSF examination or neuroimaging

  2. Headache is a direct continuation of 9.1.1 Headache attributed to bacterial meningitis

  3. Headache persists for >3 months after resolution of infection



Comments:

A reported 32% of survivors of bacterial meningitis suffer from persistent headache (Bohr et al, 1983).

There is no evidence for persistent headache following other infections, but criteria for A9.4.2 Chronic post-non-bacterial infection headache are in the appendix. More research is needed.


Bibliography and reference

9.1.1 Headache attributed to bacterial meningitis

Drexler ED. Severe headache: when to worry, what to do. Postgrad Med 1990;87:164-170, 173-180.

Francke E. The many causes of meningitis. Postgrad Med 1987;82:175-178, 181-183, 187-188.

Gedde-Dahl TW, Lettenstrom GS, Bovre K. Coverage for meningococcal disease in the Norwegian morbidity and mortality statistics. NIPH Ann 1980;3(2):31-35

Jones HR, Siekert RG. Neurological manifestation of infective endocarditis. Brain 1989;112:1295-1315.

Tonjum T. Nilsson F, Bruun JH, Hanebeg B. The early phase of meningococcal disease. NIPH Ann 1983;6:175-181.

Zhang SR, Zhang YS, Zhao XD. Tuberculous meningitis with hydrocephalus: a clinical and CT study. Chung Hua Nei Ko Tsa Chih 1989;28:202-204.



9.1.2 Headache attributed to lymphocytic meningitis

Cochius JI, Burns RJ, Willoughby JO. CNS cryptococcosis: unusual aspects. Clin Exp Neurol 1989;26:183-191.

Dalton M, Newton RW. Aseptic meningitis. Dev Med Child Neurol 1991;33:446-458.

Gomez-Arada F, Canadillas F, Marti-Masso FJ, et al. Pseudomigraine with temporary neurological symptoms and lymphocytic pleocytosis. Brain 1997;120:1105-1113.

Mak SC, Jeng JE, Jong JY, Chiang CH, Chou LC. Clinical observations and virological study of aseptic meningitis in the Kaohsinug area. Taiwan I Hsueh Hui Twa Chih 1990;89:868-872.

Pachner AR, Steere AC. Neurological findings of Lyme disease. Yale Biol Med 1984;57:481-483.

Pachner AR, Steere AC. The triad of neurologic manifestations of Lyme disease: meningitis, cranial neuritis, and radiculoneuritis. Neurology 1985;35:47-53.

Singer JI, Maur PR, Riley JP, Smith PB. Management of central nervous system infections during an epidemic of enteroviral aseptic meningitis. J Pediatr 1980;96:559-563.

9.1.3 Headache attributed to encephalitis

Brooks RG, Licitra CM, Peacock MG. Encephalitis caused by Coxiella burnetii. Ann Neurol 1986;20:91-93.

Davis LE, McLaren LC. Relapsing herpes simplex encephalitis following antiviral therapy. Ann Neurol 1983;13:192-195.

Domachowske JB, Cunningham CK, Cummings DL, Crosley CJ, Hannan WP, Weiner LB. Acute manifestations and neurologic sequelae of Epstein-Barr virus encephalitis in children. Pediatr Infect Dis J 1996;15:871-875.

Kennedy PG. Retrospective analsys of 46 cases of simplex encephalitis seen in Glasgow between 1962 and 1985. OJM 1988;86:533-540.

Kennedy PG, Adams IH, Graham DI, Clements GB. A clinico-pathological study of herpes simplex encephalitis. Neuropathol Appl Neurobiol 1998;14:395-415.

Poneprasert B. Japanese encephalitis in children in northern Thailand. Southeast Asian J Trop Med Public health 1989;20:599-603.

Saged JI, Weinstein Mo, Miller DC. Chronic encephalitis possibly due to herpes simplex virus: two cases. Neurology 1985;35:1470-1472.

9.1.4 Headache attributed to brain abscess

Chalstrey S, Pfleiderer AG, Moffat DA. Persisting incidence and mortality of sinogenic cerebral abscess: a continuing reflection of late clinical diagnosis. J R Soc Med 1991;84:193-195.

Chun CH, Johnson JD, Hofstetter M, Raff MJ. Brain abscess: a study of 45 consecutive cases. Medicine 1986;65:415-431.

Harris LF, Maccubbin DA, Triplett JN, Haws FB. Brain abscess: recent experience at a community hospital. South Med J 1985;78:704-707.

Kulay A, Ozatik N, Topucu I. Otogenic intracranial abscesses. Acta Neurochir (Wien) 1990;107:140-146.

Yen PT, Chan ST, Huang TS. Brain abscess: with spcial reference to otolaryngologic sources of infection. Otolaryngol Head Neck Surg 1995;113:15-22.

9.1.5 Headache attributed to subdural empyema

Hodges J, Anslow P, Gillet G. Subdural empyema: continuing diagnostic problems in the CT scan era. QJM 1986;59:387-393.

McIntyre PB, Lavercombe PS, Kemp RJ, McCormack JG. Subdural and epidural empyema: diagnostic and therapeutic problems. Med J Aust 1991;154:653-657.

Sellik JA. Epidural abscess and subdural empyema. J Am Osteopath Assoc 1989;89:806-810.

9.2 Headache attributed to systemic infection

De Marinis M, Welch KM, Headache associated with non-cephalic infections: classification and mechanisms. Cephalalgia 1992;12:197-201.

9.3 Headache attributed to HIV/AIDS

Brew BJ, Miller J. Human immunodeficiency virus-related headache. Neurology 1993;43:1098-1100.

Denning DW. The neurological features of HIV infection. Biomed Pharmacother 1988;42:11-14.

Evers S, Wibbeke B, Reichelt D, Suhr B, Brilla R, Husstedt IW. The impact of HIV infection on primary headache. Unexpected findings from retrospective, cross-sectional, and prospective analyses. Pain 2000; 85: 191-200.

Hollander H, Strimgari S. Human immunodeficiency virus-associated meningitis. Clinical course and correlations. Am J Med 1987;83:813-816.

Rinaldi R, Manfredi R, Azzimondi G, et al. Recurrent “migrainelike” episodes in patients with HIV disease. Headache 1007;37:443-448.

Weinke T, Rogler G, Sixt C, et al. Cryptococcosis in AIDS patients: observations concerning CNS involvement. J Neurol 1989;236:38-42.



9.4 Chronic post infection headache

Bohr V, Hansen B, Kjersen H, Rasmussen N, Johnsen N, Kristensen HS, Jessen O. Sequelae from bacterial meningitis and their relation to the clinical condition during acute illness, based on 667 questionnaire returns. Part II of a three part series. J Infect 1983 7:102-10.




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