9.1 Headache attributed to intracranial infection (WHO ICD-10NA code 44.821)

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 cerebrospinal fluid (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.

9.1.2 Headache attributed to lymphocytic meningitis

Diagnostic criteria:

A. 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 glucose.

C. Headache develops in close temporal association to meningitis.

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

9.1.3 Headache attributed to encephalitis

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, or phonophobia

B. Neurologic symptoms and signs of acute encephalitis, and diagnosis confirmed by electroencephalogram (EEG), CSF examination, neuroimaging, and/or other laboratory investigations.

C. Headache develops during encephalitis.

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

9.1.4 Headache attributed to brain abscess

Diagnostic criteria:

A. 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

B. Neuroimaging and/or laboratory evidence of brain abscess.

C. Headache develops during active infection.

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

9.1.5 Headache attributed to subdural empyema

Diagnostic criteria:

A. 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

B. Neuroimaging and/or laboratory evidence of subdural empyema.

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

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

A secondary headache is attributed to intracranial infection when a new headache occurs in close temporal relation to a proven intracranial infection. The headache disappears after successful treatment or spontaneous remission of the infection.

Such a new diffuse and often pulsating headache combined with neck stiffness, fever, photophobia, malaise, vomiting, altered consciousness, and confusion represents one of the clinical hallmarks of intracranial infections. These symptoms, clinically summarized as “meningeal syndrome,” are extremely important and constitute a serious warning sign. Intracranial infections such as bacterial meningitis, encephalitis, and brain abscesses are medical emergencies that need immediate diagnosis, antimicrobial treatment, and quite often supportive intensive care. The clinical symptoms of bacterial meningitis and certain viral diseases, including headache, progress rapidly, whereas symptoms of a brain abscess or subdural empyema may develop over a more protracted time frame. Also, headaches of subdural empyema or brain abscesses are more likely lateralized. Finally, headaches of CNS infections may exhibit characteristics of primary headaches such as migraine tension-type or cluster headache. A number of case reports indicate that various primary headache-like presentations can be encountered with intracranial infection, such as tension-type headache in patients with subacute Borrelia meningitis (8). The character and type of headache is not believed to be helpful to distinguish between underlying infectious causes, but reliable clinical data are missing.

To prove the intracranial origin or manifestation of an infection, a CSF examination is necessary. In cases of unclear fever and headache, a CSF examination is highly recommended to exclude or prove the diagnosis of CNS infection.

The diagnosis of acute CNS infections is established by:

1. Elevation of the CSF cell count and other parameters (see Table 119-1)

2. Identification of the causative microorganism by culture, Gram-stain, or polymerase chain reaction (PCR).

A computed tomography (CT) of the head is necessary prior to the lumbar puncture in the cases with focal neurologic signs and/or a disturbance of consciousness (15). To diagnose brain abscess or subdural empyema, a CT or magnetic resonance imaging (MRI) scan of the head with contrast medium is essential. Herpes simplex encephalitis, one of the most serious and acute diseases, can be diagnosed by PCR technique with a sensitivity and specificity over 90% in the first week of encephalitis (19). Other
viral diseases are harder to verify because viral cultures are unreliable, PCR sensitivity is poor, and titer changes are detected with a delay (18).

It is extremely important to recognize that the absence of headache does not exclude CNS infections. Children, elderly and immunocompromised patients, and patients with diabetes mellitus or alcohol abuse do not necessarily develop meningeal syndrome and report no or just minimal headache.

CNS infection headache usually resolves with successful antimicrobial treatment or the spontaneous remission of the disease within 1, or at most 3, months.

Headache is one of the major symptoms of the meningeal syndrome. In up to 92% of patients with proven bacterial meningitis, meningism and headache is reported (1), but the problem is more complex with viral meningoencephalitis. Headache is a major complaint in such patients with viral illness but reliable data on its incidence, and the effect of a particular agent on such incidence, are missing. Enteroviral meningitis, for example, is accompanied by severe headache in up to 90% (27). Finally, patients with brain abscess report headache as a major symptom in 65 to 90% of cases (30).

In a recent study on sudden-onset headache, only 4 out of 135 patients had lymphocytic meningitis and none had bacterial meningitis (20). This may indicate that in acute diseases such as bacterial meningitis, headache is covered by other symptoms or summarized as a part of meningeal irritation. This hypothesis needs further testing in large observational studies.

Headache and meningism are clinical manifestations of meningeal irritation (Fig. 119-1). Bacteria as well as viruses may directly activate meningeal nerve fibers and cause neuropeptide release. Neuropeptides are significantly raised in the CSF of patients with proven bacterial meningitis (17). Active bacterial metabolism engenders toxic products, such as H₂O₂ and pore-forming toxins. In addition, bacterial cell wall and surface structures, such as peptidoglycan, lipoteichoic acids, and lipopolysaccharide, may directly activate sensory nerve fibers in the meninges. These components induce several inflammatory mediators in different relevant cell types including endothelial cells and microglia (28). Cytokines and nitric oxide (NO) are mediators known to play a role in headache (26).

CNS infections are characterized by a significant influx of activated leukocytes, which in turn may add to the activation of meningeal nerve fibers (Fig. 119-2). Increased blood flow and cytotoxic effects contribute to brain edema, which may cause tension on the meninges. As in other
conditions, edema and space-occupying lesions in encephalitis, brain abscess, and empyema can cause headache.