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Infectious Diseases of the Brain and Meninges 75

Infectious Diseases of the Brain and Meninges


(695, 835, 960, 1024)

Overview:
Pathogenic organisms may reach the central nervous system by hematoge-
nous spread or local extension and cause infections of the meninges (men-
ingitis), infections of the brain and spinal cord parenchyma (encephalitis,
myelitis), focal purulent collections (brain abscess, subdural empyema,
epidural abscess), or infections of the nerve roots (radiculitis, polyradiculi-
tis). Depending on the causative organism, the infection may take an acute,
subacute or chronic course and may be self-limiting or destructive and life-
threatening. Prions are the causative agents of several neurodegenerative
diseases. Many CNS infections can be treated if diagnosed in timely fash-
ion. The cerebrospinal fluid examination, including culture, and neuro-
imaging studies (CT and MRI), together with the clinical findings, are gen-
erally sufficient to enable a differentiation among bacterial, viral, mycotic,
and parasitic pathogens and a precise etiologic diagnosis. In general, anti-
microbial therapy is given on an empirical basis until the causative organ-
ism is identified and the treatment can be tailored to it.

Meningitis is an infection of the pia- Infectious organisms reach the cen-


arachnoid and of the cerebrospinal tral nervous system by hematoge-
fluid in the subarachnoid space. Be- nous spread, local extension, or,
cause the subarachnoid space con- rarely, by direct (mechanical) inocu-
tains no anatomical barriers, menin- lation, as in open head injuries. Sys-
gitis can spread without hindrance temic parameters of inflammation
over the entire surface of the brain are almost always abnormal, but to
and into the spinal canal and cerebral differing degrees. Nearly all known
ventricles (ventriculitis). A more or infectious agents may involve the
less diffuse infection of the brain pa- central nervous system. In this chap-
renchyma is called encephalitis, and a ter, we discuss those that the neurol-
focal collection of pus cerebritis (in ogist encounters most frequently.
the early stage) or brain abscess (in
the late stage). A collection of pus in
the (virtual) space between the dura
mater and the arachnoid is called a
subdural empyema, and one overlying
the dura mater an epidural abscess
(Fig. 2.13). As for infections affecting
the spinal cord, see p. 414.

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76 2 Diseases Mainly Affecting the Brain and its Coverings

a Sinus sagittalis
superior

6
Dura
5 mater

Arachnoidea
1
Subarach-
noidalraum
2 3 4 Pia mater

b
Kortex

Substantia alba

Periost

Epiduralraum
5
Dura mater
1

2 Arachnoidea

Subarachnoidalraum
6
Pia mater

Rckenmark : Gehirn :
1 = Arachnoiditis 1 = Meningitis
2 = Myelitis 2 = Enzephalitis
3 = Zerebritis (= Frhstadium)
Hirnabszesse
4 = Abszess (= Sptstadium)
5 = spinaler Subduralabszess 5 = subdurales Empyem
6 = spinaler Epiduralabszess 6 = Epiduralabszess

Fig. 2.13a, b Localization and nomenclature of intracranial and spinal infections.


a Intracranial infections.
b Spinal infections.

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Infectious Diseases of the Brain and Meninges 77

Ancillary Tests in the Evaluation of Suspected CNS Infection


| Cerebrospinal Fluid Examination (308)
Definition:
The cerebrospinal fluid is examined for the diagnosis or exclusion of infec-
tious or demyelinating diseases of the brain, meninges, spinal cord, and
nerve roots, of subarachnoid hemorrhage, and of carcinomatous or sarco-
matous meningitis. A sample of cerebrospinal fluid can be obtained by
lumbar puncture or, in exceptional cases, by suboccipital puncture.

Indications | Lumbar Puncture


The indications for cerebrospinal The most important consideration for
fluid examination should be liberal, a successful lumbar puncture is the
as imaging studies may fail to detect positioning of the patient (Fig. 2.14).
acute bacterial meningitis and CT- The head should be at the same level
negative subarachnoid hemorrhage. as the puncture site. The shoulders
should be vertically superimposed so
Contraindications that there is no torsion of the spine. If
The following are absolute contraindi- the patient is agitated or uncoopera-
cations to lumbar and suboccipital tive, one or more assistants can hold
puncture: the patients head and knees from the
> clinical evidence of intracranial hy- front.
pertension; Orientation is facilitated by the line
> platelet count under 5,000. connecting the two posterior supe-
rior iliac spines, which usually inter-
The following are relative contraindi- sects the spinous process of L4. The
cations: puncture may be one segment higher
> anticoagulation; or one or two segments lower.
> platelet count 5,00020,000; The physician wears sterile gloves.
> lumbar paraspinal abscess or other The skin is prepared with disinfectant
infection. and local anesthesia is injected at the
intended puncture site. It is impor-
The risks of lumbar puncture are: tant to wait 12 minutes for this to
> transtentorial or transforaminal take effect. The puncture is per-
herniation, if the intracranial pres- formed with an 810-cm long spinal
sure is dangerously elevated; needle with stylet, strictly in the mid-
> clinical worsening of paraparesis, if line and aiming approximately 30 de-
there is a partial block to the flow grees upward, through the tough in-
of cerebrospinal fluid; terspinous ligament. If bony resis-
> epidural, subdural, and subarach- tance is felt, the needle should be par-
noid hemorrhage. tially withdrawn and reintroduced in
another direction, usually more cra-
The risk of bleeding after lumbar nial than before. Penetration of the li-
puncture in patients with normal co- gamentum flavum is felt as a brief
agulation status is less than 1 %. pop as the resistance to passage of

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78 2 Diseases Mainly Affecting the Brain and its Coverings

Fig. 2.14 Lumbar puncture.

the needle momentarily increases, ciated with torsion of the spine; in


then decreases. such situations, an L5/S1 puncture is
After removal of the stylet, the cere- recommended, because torsion is
brospinal fluid should emerge spon- least at this level. If difficulties are en-
taneously. If this is not the case, the countered for this or other reasons,
angle of the opening at the needle tip the puncture can also be performed
should be changed by a partial rota- on the patient in the sitting position,
tion of the needle. If still no fluid is and the patient can be laid horizontal
seen, the stylet should be reinserted again after successful puncture.
and the needle introduced a bit far- Once cerebrospinal fluid is seen
ther. If the patient complains of a emerging from the needle, its pres-
sudden pain radiating into the leg, it sure should be measured in mmH2O
is because the needle has irritated a with a manometer. Compression of
nerve root; it should be partially the jugular veins with a hand pressed
withdrawn and reintroduced at a new flat against the neck impedes cere-
angle, away from the side on which brospinal fluid resorption and thus
pain was reported. The correct depth raises the intracranial pressure; this
of insertion varies: in very obese pa- rise ought to be reflected in a corre-
tients, the needle may need to be in- sponding rise of the lumbar cerebro-
serted to the hilt, while infants rarely spinal fluid pressure (Queckenstedt
require an insertion deeper than test). In a positive (normal) Queck-
2.5 cm (119). If it is in proper position, enstedt test, the fluid column in the
but no fluid emerges, low cerebrospi- manometer promptly rises, demon-
nal fluid pressure is a possibility and strating the patency of the spinal ca-
this should be checked by gently as- nal and the jugular veins; a negative
pirating on the needle with a sterile test indicates the presence of an ob-
syringe. Lumbar puncture may be struction. External pressure on the
particularly difficult in the presence abdomen or abdominal straining can
of scoliosis, which is always asso- raise the pressure in the lumbar

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Infectious Diseases of the Brain and Meninges 79

spinal canal even if an obstruction to Indications


cerebrospinal fluid flow is present at Suboccipital puncture is indicated
a higher (cervical or thoracic) level, so only when:
this test cannot be used to rule out an > meningitis is suspected, but a lum-
obstruction. Poor needle position bar puncture yields no cerebrospi-
with partial misplacement of the nal fluid for examination; or
opening at the tip of the needle may > lumbar puncture is contraindicated
result in a falsely abnormal Queck- by an infectious process in the lum-
enstedt test. bar region.
Once the pressure has been mea-
sured, a sufficient quantity of cere-
brospinal fluid is collected for the de- | Laboratory examination of
sired diagnostic tests. For both medi- cerebrospinal fluid and
cal and medicolegal reasons, the pa- interpretation of findings
tients informed consent should be Normal values for the most important
obtained beforehand, and the proce- cerebrospinal fluid tests are listed in
dure should be documented in the Tables 2.19 and 2.20.
hospital chart.
The patient should lie prone for Gross appearance. The cerebrospinal
1 hour and flat in bed for at least a fluid is normally clear and colorless.
further 8 hours after the procedure, to Cloudy cerebrospinal fluid indicates
lessen the chance that cerebrospinal meningitis, while bloody or xan-
fluid will leak from the dural punc- thochromic fluid indicates subarach-
ture site into the epidural space, pro- noid hemorrhage. Bloody cerebrospi-
duccing a low fluid pressure syn- nal fluid may also be the artefactual
drome (see p. 819). In general, this result of a traumatic puncture. Truly
risk can also be reduced by the use of bloody cerebrospinal fluid can be dif-
a finer needle. The risk is so low with ferentiated from a bloody tap by the
the Sprotte needle (which is very fine, so-called three tube test, in which
and has a blunt tip with a lateral three tubes are filled with cerebrospi-
opening) that the procedure can be nal fluid, one after the next. Truly
performed on an outpatient basis. bloody cerebrospinal fluid is equally
bloody in all three tubes, while the
| Suboccipital Puncture fluid gradually clears from each tube
Suboccipital puncture is performed to the next after a traumatic punc-
under fluoroscopic guidance by ei- ture. Xanthochromia of centrifuged
ther of two possible approaches: cerebrospinal fluid may also be help-
> Dorsomedian approach in the sit- ful in this regard: it is absent after a
ting or laterally recumbent patient. traumatic puncture, but present
The cisterna magna is punctured within 610 hours of a subarachnoid
between the lower rim of the oc- hemorrhage. By the same token,
cipital bone and the posterior arch however, the absence of xanthochro-
of C1 (cisternal puncture). mia in the first few hours after the
> Lateral approach in the supine pa- presenting event does not rule out a
tient. The subarachnoid space is subarachnoid hemorrhage. Xan-
entered between C1 and C2 (lateral thochromia may be present in jaun-
cervical puncture). diced patients, as well as those with

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80 2 Diseases Mainly Affecting the Brain and its Coverings

extreme hyperproteinemia. Mild de- tion or an actual infection; higher val-


grees of xanthochromia can be de- ues practically always indicate men-
tected by spectroscopy if visual in- ingitis. The cerebrospinal fluid pic-
spection is inconclusive. ture of acute inflammation is domi-
nated by neutrophils. In the subacute
Total and differential cell count. Nor- phase, there are fewer neutrophils;
mal cerebrospinal fluid contains no monocytes and macrophages (some of
erythrocytes and up to four leuko- which contain phagocytosed neutro-
cytes per microliter. Lymphocytes phils and lymphocytes) predominate,
predominate ( n 70 %), and monocytes and eosinophils may herald the be-
are rarer ( p 30 %). An elevation of the ginning of the regenerative response.
total leukocyte count to 30 per micro- The chronic phase is associated with a
liter in the presence of a few neutro- lymphocytic picture; many trans-
phils and macrophages may repre- formed lymphocytes and plasma cells
sent either a nonspecific inflamma- are present.

Table 2.19 Normal values in cerebrospinal fluid and serum in adults1

Cerebrospinal fluid Serum

Pressure 518 cmH2O


Volume 100160 mL
Osmolarity 292297 mosm/L 285295 mosm/L
Electrolytes
> Na 137145 mmol/L 136145 mmol/L
> K 2.73.9 mmol/L 3.55.0 mmol/L
> Ca 11.5 mmol/L 2.22.6 mmol/L
> Cl 116122 mmol/L 98106 mmol/L
pH 7.317.34 7.387.44
Glucose 2.23.9 mmol/L 4.26.4 mmol/L
> CSF/serum glucose quotient G 0.50.6
Lactate 1.02.0 mmol/L 0.61.7 mmol/L
Total protein 0.20.5 g/L 5580 g/L
> Albumin 5675 % 5060 %
> IgG 0.0100.014 g/L 815 g/L
> IgG index 2 X 0.65
Leukocytes X 4/ L
Lymphocytes 6070 %
1 Because serum and cerebrospinal fluid are in equilibrium, simultaneous measurement
of values in both is recommended.
2 IgG index = CSF IgG (mg/dL) serum albumin (g/dL) / serum IgG (g/dL) CSF albumin
(mg/dL).

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Infectious Diseases of the Brain and Meninges 81

Table 2.20 Clinically useful investigations while a predominantly lymphocytic


of cerebrospinal fluid pleocytosis indicates viral infection.
Nonetheless, the cerebrospinal fluid
Routine investigations:
picture may be predominantly granu-
> Pressure, Queckenstedt test
locytic in the initial phase of an acute
> Color (turbidity? xanthochromia?
bloody tinge?)
viral meningitis. A chronically inflam-
> Absolute and differential cell count matory cerebrospinal fluid picture is
> Protein found in the healing phase of bacte-
> Glucose rial meningitis and in fungal and par-
asitic infections, borreliosis (Lyme
Selectively applied investigations: disease), syphilis, and sarcoidosis.
> Immunoglobulin The presence of many eosinophils is a
> IgGalbumin index distinguishing feature of parasitic in-
> Oligoclonal bands fection. In tuberculosis, the cellular
> Specific testing for IgG, IgA, and IgM picture is usually subacutely or
against Borrelia, parasites, and viruses chronically inflammatory. Erythro-
> Bacterial, fungal, viral, and mycobac-
cytes may be a component of an in-
terial culture
flammatory cerebrospinal fluid pic-
> Gram and Ziehl-Neelsen stain, touch
ture (hemorrhagic encephalitis) or
prep
> VDRL and FTA tests for syphilis
may result from a subarachnoid hem-
> Cytological examination for malignant
orrhage of noninflammatory etiology.
cells Neoplastic cells are shed into the cere-
> DNA amplification (PCR) for tubercu- brospinal fluid by a number of pri-
losis and viral pathogens mary brain tumors, including epen-
> Cystatin C in amyloid angiopathy dymoma, choroid plexus papilloma,
(872) germinoma of the pineal region, and
> Antineuronal antibodies in paraneo- medulloblastoma. The presence of
plastic syndrome (207) carcinoma or sarcoma cells indicates
meningeal metastatic spread, most
After a traumatically bloody lumbar commonly of breast cancer, lung can-
puncture, the true lymphocyte count cer, or melanoma. Leukemia and lym-
in the patients cerebrospinal fluid phoma may also involve the menin-
(LCP) may be approximately calcu- ges.
lated on the basis of the measured
lymphocyte and erythrocyte counts Cerebrospinal fluid protein. After the
in the fluid obtained by lumbar punc- cell count, the protein concentration
ture (LCL and ECL) and in the blood is the most important value to be de-
(LCB and ECB), as follows: termined (Table 2.21). An elevation of
the protein concentration without
(LCB ECL)
LCP = LCL any corresponding elevation in cell
ECB
count (so-called albuminocytologic
An elevated cell count of up to a few dissociation) is a classic, albeit non-
hundred cells per microliter is etio- specific, finding in Guillain-Barre
logically nonspecific. In general, an syndrome and is also present in dia-
acutely inflammatory cerebrospinal betes. An elevated IgG index (see
fluid picture with a cell count of over Table 2.20) indicates intrathecal IgG
1000/ L indicates bacterial infection, production by an intrathecal inflam-

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82 2 Diseases Mainly Affecting the Brain and its Coverings

Table 2.21 Diseases associated with ele- matory process (588, 941). The gam-
vated cerebrospinal fluid protein concen- maglobulins can be nonquantitatively
tration separated by electrophoresis into
Elevated protein with elevated cell mono-, poly- and (usually two to five)
count: oligoclonal bands. Isoelectric focusing
> Acute and chronic meningitides and is a more sensitive test, based on the
encephalitides different isoelectric points of differ-
> Bacterial ent proteins, which can be combined
> Viral
with immune fixation (the use of spe-
> Fungal
cific antisera) (938) for still greater
> Spirochetal
sensitivity. Oligoclonal bands found
> Parasitic
> Neoplastic
in the cerebrospinal fluid, but not in
> Chemical/physical an appropriately diluted serum sam-
> Poliomyelitis ple tested alongside it, are indicative
of an inflammatory process in the
Protein elevation [ cell count eleva- central nervous system. Such CSF-
tion:
specific bands are found in more than
> Acute inflammatory polyradiculitis 90 % of patients with multiple sclero-
(Guillain-Barr
e syndrome) sis, and less commonly in patients
> Chronic inflammatory demyelinating with other types of central nervous
polyneuropathy (CIDP)
>
disease.
Tabes dorsalis, meningovascular
syphilis
> Myxedema Glucose. The concentration of glucose
> Diabetes mellitus in the cerebrospinal fluid is 5060 %
> Schwannoma of that in serum. Thus, a CSF glucose
> Chronic arachnoiditis concentration that is normal in abso-
> Status post subarachnoid hemorrhage lute terms may be abnormally low if
> Cerebral venous (and venous sinus) the serum glucose concentration is
thrombosis
elevated, and a low CSF glucose con-
> Brain tumors
>
centration may be normal in hypogly-
Metachromatic leukodystrophy
> Obstructed CSF flow at spinal level
cemia. Diseases associated with CSF
(Froin syndrome) pleocytosis lower the CSF glucose
> Vitamin B12 deficiency concentration, particularly chronic
> Mitochondrial encephalomyelopathy meningitides (Table 2.22).
Elevated protein with or without ele-
vated cell count:
| Brain Biopsy
> CNS vasculitis A biopsy is an invasive diagnostic
> Gliomatosis cerebri procedure that should only be per-
> Epidural abscess formed after a careful consideration
of the indications and when all rele-
Mildly elevated protein with or without
mildly elevated cell count: vant noninvasive studies have failed
to yield a diagnosis.
> Multiple sclerosis Brain biopsy is a neurosurgical proce-
> Epilepsy dure that can be performed either
> Brain infarct
> Abscess
through an open craniotomy, or ste-
> Uremia
reotactically under radiologic guid-
ance. In most centers, its use is re-

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