104 2 Diseases Mainly Affecting the Brain and its Coverings

Treatment
The viral encephalitides are treated
symptomatically, with the goal of
preventing medical complications.
Temporary hospitalization in an in-
tensive care unit is often necessary,
especially when respiratory dys-
function arises. If HSV encephalitis
is suspected, acyclovir should be
given (see above for dosage). Other
CNS infections entering into the
differential diagnosis that may re-
quire other kinds of specific treat-
ment should be ruled out with cer-
tainty. Cerebral edema exerting
mass effect must be treated (p. 72)
whenever there is clinical or radio-
logical evidence for its presence.
Fig. 2.22 Progressive multifocal leu-
Decisions whether to give anticon-
koencephalopathy.
A 75-year-old man with leukemia and corti- vulsants or ulcer prophylaxis
cal blindness. The signal change in the should be made on an individual
white matter is typical, as are the un- basis.
changed signal intensity and thinning of
the adjacent gray matter (arrows).
other relevant physical findings or
suggestive history may be absent.
Occasionally, erythema chronicum
Chronic Meningitis (955)
migrans will point to a diagnosis of
Chronic meningitis is diagnosed borreliosis (Lyme disease), or the fun-
when the clinical signs and symp- duscopic examination will reveal
toms of meningitis, including inflam- signs of chorioretinitis. Rarely (e.g., in
matory changes of the cerebrospinal sarcoidosis), there may be signs of
fluid, persist for at least 4 weeks. The hypothalamic or pituitary dysfunc-
various etiologies are summarized in tion. Cranial nerve deficits are found
Table 2.29. Their frequency varies more often in tuberculous, sarcoid,
highly in immune-competent and luetic, fungal, and neoplastic menin-
immunocompromised patients (p. gitis, all of which preferentially affect
120). Relevant aspects of the patients the basilar meninges.
history include earlier illnesses, oper-
ations and malignancies, travel, tick Diagnosis
bites, sexual behavior, and eating A complete blood count, serum en-
habits. zymes, antinuclear antibodies, serol-
ogy for HIV, syphilis, and cryptococ-
Clinical Features cus, and a chest roentgenogram
The most prominent manifestations should be obtained in every patient.
are headache, fever, and nuchal rigid- Cutaneous lesions may point to the
ity, but these may be very mild, and correct diagnosis in borreliosis, sar-

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 Infectious Diseases of the Brain and Meninges 105

Table 2.29 Common etiologies and differential diagnoses of chronic meningitis (after
272)

Infectious
> Bacterial and mycobacterial Tuberculosis
Brucellosis
> Fungal Cryptococcosis
Candidiasis
Coccidioidomycosis (in North America)
Histoplasmosis (in the United States)
> Spirochetal Syphilis
Borreliosis (Lyme disease)
> Parasitic Cysticercosis
Echinococcosis
> Viral HIV
Non-infectious Neoplastic meninigitis
Sarcoidosis
Granulomatous vasculitis
Isolated CNS vasculitis
Systemic lupus erythematosus
Behcets disease
Vogt-Koyanagi-Harada syndrome
Differential diagnosis Parameningeal inflammatione.g., epidural abscess,
osteomyelitis

coidosis, secondary syphilis, tubercu- chyma (e.g., in cysticercosis, toxoplas-

losis, or disseminated fungal infec- mosis, and tuberculosis), and the
tion. The cerebrospinal fluid exami- chronically inflamed meninges en-
nation should include cell count, hance with intravenously adminis-
protein, glucose, Gram and Ziehl- tered contrast (see Fig. 2.15). Imaging
Neelsen stains, syphilis and Borrelia studies are also necessary to rule out
serologies, a touch prep for the dem- the presence of parameningeal foci of
onstration of cryptococcus, and cytol- infection, hydrocephalus complicat-
ogy for the detection of neoplastic ing chronic basilar meningitis, and
cells (p. 79). multiple infarcts due to vasculitis.
Further, the cerebrospinal fluid Vasculitis can be ruled out by angiog-
should be cultured for aerobic and raphy. Because chronic meningitis
anaerobic bacteria, fungi, and tuber- may be the central nervous manifes-
cle bacilli. These tests should be per- tation of an infection involving other
formed at least three times, both to organs as well, the lymph nodes, liver,
increase the diagnostic yield and to and bone marrow may need to be bi-
assess the dynamics of the disease opsied, and the gastric juice, sputum
over time. and urine may need to be cultured for
A CT or, preferably, MRI scan may in- mycobacteria and other pathogens,
dicate a lesion of the brain paren- depending on the specific clinical

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106 2 Diseases Mainly Affecting the Brain and its Coverings

Table 2.30 Diagnostic questions and investigations to be considered in chronic

meningitis

MRI of brain with contrast, possibly CT

(parenchymal lesion, meningeal or parameningeal involvement?)
MRI of spinal cord with contrast, possibly CT
(parenchymal lesion, meningeal or parameningeal involvement?)
Plain radiographs of skull and spine (bone destruction?)
Cerebrospinal fluid examination, at least 3 times
(cell count, protein, isoelectric focusing, glucose, Gram stain, touch prep, Ziehl-
Neelsen stain, cytology for neoplastic cells, cultures for aerobic and anaerobic
bacteria, fungi, and mycobacteria, PCR studies, possibly also antibody tests)
Funduscopy with contact lens (chorioretinitis?)
Serological studies
(borreliosis, syphilis, HIV, brucellosis, cryptococcosis, toxoplasmosis, cysticercosis,
echinococcosis, antinuclear antibodies, etc.)
Medication history
(medication-induced aseptic meninigitis? intravenous immunoglobulins?)
Mycobacterial culture of sputum, gastric juice, and urine
Angiotensin-converting enzyme (sarcoidosis?)
Tuberculin test (sarcoidosis, tuberculosis?)
Chest radiograph (sarcoidosis, tuberculosis, or other specific change?)
Cerebral angiography (vasculitis?)
Tissue biopsy for histology, possibly also microbiological examination and culture
(skin, liver, bone marrow)
Biopsy and possibly also microbiological examination and culture of radiologically
detectable abnormalities in the meninges or brain

suspicion in each case. If the diagno- (622). In a recent study, PCR analysis
sis remains unclear, the neuroradiolo- demonstrated the presence of HSV-II
gically visible changes in the menin- in patients cerebrospinal fluid dur-
ges or brain should be directly inves- ing, but not between, the meningitic
tigated by biopsy and culture. The episodes; this illness is thus thought
neurosurgeon should also take this to represent an initial infection with
opportunity to obtain ventricular HSV-II followed by one or more epi-
fluid for culture (Table 2.30). sodes of reactivation. It remains un-
clear whether virustatic therapy can
Recurrent Meningitis shorten the meningitic episodes. It
The syndrome of recurrent aseptic seems reasonable to treat frequently
meningitis with symptom-free inter- recurring episodes with famciclovir,
vals is known as Mollarets meningitis 500 mg p.o. b.i.d., for 10 days.

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 Infectious Diseases of the Brain and Meninges 107

Allergic reactions to medications, Table 2.31 Types of fungal infection in

usually nonsteroidal anti-inflam- the CNS (after Bell and McGuinness, 80)
matory agents, can also produce re-
Meningitis (acute, subacute, chronic)
current meningitis (195). Further
causes include acquired or congenital Granulomatous meningoencephalitis
dural defects, epidermoid cyst, or a
Abscess (solitary, multiple, microabscess)
parameningeal infection that repeat-
edly breaks into the subarachnoid Granuloma (microgranuloma, mass le-
space. sion)

Treatment Infarct due to arterial or venous throm-

bosis
When chronic meningitis is due to
a known pathogenic organism, the
treatment is directed at its eradica-
tion. Usually, however, the etiology in Europe. Coccidioides immitis is
is not yet known when a therapeu- found only in the Americas, Histo-
tic decision must be taken. When plasma capsulatum worldwide but
borreliosis is suspected, ceftriaxone with a particular concentration in the
can be given for 3 weeks. If the pa- Americas, and Blastomyces dermatiti-
tients condition worsens despite dis in North America, Africa, and the
this treatment, tuberculostatic Middle East.
treatment should be given without
hesitation. In such situations, a | Cryptococcosis
possible fungal infection should be Cryptococcus neoformans mainly af-
sought by all available diagnostic fects patients with AIDS or other sys-
means, even while tuberculostatic temic illnesses impairing the cellular
treatment is in progress, and, if dis- immune response (lymphoma, post-
covered, should be treated. If fungi transplantation, steroid therapy), and,
are not found, and if the level of more rarely, patients with normal im-
clinical suspicion for a fungal infec- mune status (231, 1050). The primary
tion is not very high, then empiri- infection occurs in the lungs. CNS in-
cal antifungal therapy should not fection is usually subacute or chronic
be given, in view of its high toxicity. and appears as a combination of
meningitis and multifocal granulo-
matous encephalitis (the clinical
Fungal Meningoencephalitis
signs of either of these two may pre-
The clinical features of fungal infec- dominate in individual cases). The
tion cover a broad spectrum (Table major symptom is headache, and as-
2.31). The immune status of the pa- sociated signs of encephalitis include
tient is a crucial variable. Cryptococ- personality changes, confusion, and
cus neoformans is the most common focal neurological deficits. In some
pathogen in the patient with normal cases, a mild cognitive deficit is the
immune status, while Candida sp. and only manifestation of disease. The ce-
Aspergillus sp. are more common in rebrospinal fluid examination usually
the immunocompromised host. In reveals a chronically inflammatory
general, fungal illness plays a greater picture (p. 84 and Table 2.22), which
role in arid geographic zones than may be only mild in the presence of

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108 2 Diseases Mainly Affecting the Brain and its Coverings

Table 2.32 Fungi causing CNS infections, gical procedures, intravenous cathe-
in order of frequency (after Bell and terization, steroid treatment, intrave-
McGuinness, 80) nous drug use, and the like. It may
take an acute or chronic course, with
In patients with normal immune status:
or without fever, and lead to menin-
> Cryptococcus neoformans gitis or meningoencephalitis, with
> Coccidioides immitis corresponding clinical features. The
> Histoplasma capsulatum cerebrospinal fluid examination usu-
> Blastomyces dermatitidis ally reveals a chronically inflamma-
> Sporothrix schenckii tory picture (see Table 2.21), with cell
In the immunocompromised host: count rarely above 2000/ L. The
> Candida spp. diagnosis rests on the demonstration
> Aspergillus spp. of spores in the cerebrospinal fluid,
> Zygomycetes (Phycomycetes) either directly or by culture.
> Cryptococcus neoformans
> Histoplasma capsulatum Treatment
> Blastomyces dermatitidis Candidiasis is treated with ampho-
> Sporothrix schenckii tericin B and flucytosine.
> Others

Parasitic Diseases of the Brain

immunosuppression. The touch prep
directly reveals cryptococci in more | Toxoplasmosis (542)
than half of all patients; when it does Toxoplasma gondii is an intracellular
not, the demonstration of anticrypto- parasite. Infection may be congenital,
coccal antibodies in the serum and or it may be acquired at any age
cerebrospinal fluid is necessary for through the consumption of infected
rapid diagnosis. CSF cultures are posi- meat or contact with the feces of do-
tive by 46 weeks in three-quarters of mestic animals or pets.
all patients. Blood, sputum, urine, and Congenital toxoplasmosis produces a
stool cultures may also be helpful. granulomatous meningoencephalitis
(p. 36).
Treatment Acquired toxoplasmosis is typically
asymptomatic or else a mono-
The treatment consists of amphote-
nucleosis-like illness with lymphade-
ricin B and flucytosine. Immuno-
nopathy, fever, rash, myalgias, and
compromised patients require
hepatosplenomegaly. In rare cases,
long-term treatment with flucyto-
meningoencephalitis may be seen,
sine for the prevention of a relapse.
with up to 500 lymphocytes per mi-
croliter of cerebrospinal fluid (948).
| Candidiasis (77) Patients with AIDS or under pharma-
Candidiasis is seldom restricted to cological immunosuppression are at
the central nervous system and gen- increased risk of severe toxoplasmo-
erally is found in the CNS as a local sis infections, which may arise de
expression of systemic disease. It is novo or as a reactivation of latent dis-
usually a consequence of visceral sur- ease.

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 Infectious Diseases of the Brain and Meninges 109

Clinically, there may be a diffuse me- eggs, which then develop into em-
ningoencephalitis, or else solitary or bryos; the latter penetrate the intesti-
multiple intracerebral masses (698). nal wall and spread through the
Gradually worsening headache, leth- bloodstream to the distant soft tis-
argy, seizures, and focal neurologic sues, including the brain, where they
signs are typical manifestations. CT mature further to larvae (cysticerci).
and MRI reveal solitary or multiple
ring-enhancing lesions (464, 806),
which may become calcified. The di-
agnosis is established by serology or
by the direct demonstration of organ-
isms in tissue or cerebrospinal fluid.

Treatment
The treatment of choice is a combi-
nation of pyrimethamine and sulfa-
diazine, together with leucovorin
(see Table 2.26).

a
| Amebic, Plasmodial, and
Trypanosomal Infections
These protozoal illnesses affecting
the brain are mainly found in Africa
and the Americas.

| Cysticercosis
Cysticercosis is endemic to Central
and South America and parts of Af-
rica, Asia, and Eastern Europe. Is
caused by the pork tapeworm (ces-
tode), Taenia solium. Man is the only
known definitive host for the adult
form of the organism (the tapeworm
itself, which resides in the intestine).
Man may also be infected as an inter-
mediate host, harboring the larvae of
the organism in skeletal muscle and
in the brain (cerebral cysticercosis). b
The commonest intermediate hosts Fig. 2.23a, b Cerebral cysticercosis.
are domestic animals such as pigs, a Parasagittal T1-weighted image. Two
cysts are visible as hypodense areas in
dogs, cats, and sheep. When a human
the parietal lobe. A larva can be seen in
being eats the flesh of an infected an- the larger cyst.
imal that contains larvae, an intesti- b Axial T2-weighted image. Two cysts can
nal infection with the adult tape- be seen as areas of increased signal lat-
worm results. The worm produces eral to the left posterior horn.

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110 2 Diseases Mainly Affecting the Brain and its Coverings

The cysticerci may be several milli- multilocularis to locally invasive cyst

meters to 2 cm in size. Their clinical agglomerates that are usually found
manifestations are a function of their in the liver, lungs, and skeletal mus-
size, number, localization, and stage cle. The larvae may rarely stray into
of development, together with the re- the brain, where they form solitary
action of the surrounding cerebral mass lesions that progress over sev-
tissue (833). They most commonly eral months and cause epilepsy,
cause epileptic seizures (224), head- headache, papilledema, personality
ache, papilledema, and vomiting, and changes, and focal neurologic deficits.
more rarely hydrocephalus, meningi- The diagnosis is made on the basis of
tis, or spinal cord involvement. the neuroradiologic findings and se-
CT and MRI are essential for the diag- rology, which is usually, though not
nosis (173) and reveal single or multi- always, positive.
ple cystic lesions, sometimes contain-
ing radiologically identifiable larvae Treatment
(Fig. 2.23). Cysts should be neurosurgically re-
The dying cysticercus causes an in- sected whenever possible. If the
flammatory tissue reaction with cyst is unresectable, albendazole
edema and then becomes calcified. can be given.
The cerebrospinal fluid may be nor-
mal or show chronic inflammation,
with eosinophils. The diagnosis is es- | Nematoid Infections
tablished by serology or by direct Trichinosis is the most common ne-
demonstration of cysticerci in biop- matoid infection affecting man and is
sied tissue. usually contracted by the consump-
tion of undercooked pork. The in-
Treatment gested larvae spread through the
bloodstream to the soft tissues. After
Praziquantel and albendazole are
an initial diarrheal phase, the disease
given in combination with cortico-
manifests itself by fever, prostration,
steroids (albendazole is more effec-
myalgias due to myositis, periorbital
tive against neurocysticercosis
edema, and, in 10 % of cases, meningi-
than praziquantel). Cysts must oc-
tis, encephalitis, or meningoencepha-
casionally be removed neurosur-
litis. Eosinophilia in the peripheral
gically (190).
blood is present, indicating a parasitic
infection. The diagnosis is established
| Other Cestoid Infections by serology or muscle biopsy.
The larval form of other tapeworms
(cestodes) may cause infections in Treatment
man, including coenurosis, spargano- Steroids (prednisone, 1 mg/kg, for
sis, and echinococcosis. 5 days) are effective against myosi-
tis, but antihelminthic agents are
Echinococcosis. This disease is caused ineffective against the larvae in the
by the larvae of tapeworms for which soft tissues.
dogs and foxes are the definitive
hosts. Echinococcus granulosus gives
rise to solitary cysts, Echinococcus

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 Infectious Diseases of the Brain and Meninges 111

| Rickettsial Infections (1034) Spirochetal and Leptospiral

Rickettsiae are intracellular parasites Infections
that cause a number of illnesses in-
cluding Rocky Mountain spotted fe-
| Neurosyphilis (662, 1003)
ver, louse-born typhus, Q fever, and Syphilis (lues) is a chronic, sexually
trench fever. These illnesses are transmitted infection caused by the
transmitted by ticks, lice, and fleas. spirochete Treponema pallidum. Its
Central nervous system involvement three phases are known as primary,
is indicated by the presence of head- secondary, and tertiary syphilis.
ache and other neurologic manifesta- Syphilitic meningitis may occur as
tions and may dominate the clinical early as the secondary phase, but typ-
picture. Serologic tests are available ical neurosyphilis occurs in the ter-
for most of the rickettsioses. tiary phase. Neurosyphilis may be
meningeal, meningovascular, or paren-
Treatment chymal; in the latter form, it is associ-
ated with the classical syndromes of
Tetracycline and chloramphenicol
general paresis (earlier known as
are the antimicrobial agents of first
general paresis of the insane) and
choice.
tabes dorsalis. If the patient is clini-
cally asymptomatic and serologic
tests are positive only in the blood,
Encephalopathies Caused by then one speaks of seropositive latent
Immune Reaction (469) syphilis; if serologic tests are positive
Certain infectious diseases and im- in the cerebrospinal fluid as well, one
munizations rarely provoke immune speaks of asymptomatic neurosyphi-
reactions leading to complications in lis. Cerebrospinal fluid changes ap-
the central nervous system. An in- pear in one-third of all syphilitic in-
flammatory, demyelinating encepha- fections, usually between 12 and
lomyelitis typically arises days to 18 months after the primary infec-
weeks after the infection or immuni- tion, at which time meningovascular
zation, with a monophasic course. syphilis is also most frequent. General
Post-vaccinial and post-infectious en- paresis or tabes dorsalis appears
cephalomyelitides are most often years or even decades after the pri-
seen after rabies and measles immu- mary infection in 7 % of all untreated
nizations or after a measles infection syphilitics.
(p. 130), mumps, chickenpox, or ru-
bella (360). | Meningeal Syphilis
Cerebrospinal fluid pleocytosis is Meningeal syphilis may affect the
usually present, and MRI reveals mul- meninges of either the brain or the
tifocal signal changes (509). The dif- spinal cord and manifests itself as
ferential diagnosis between one of headache, vomiting, meningism, cra-
these entities and the initial phase of nial nerve deficits, papillitis, seizures,
multiple sclerosis may be impossible and occasionally mental changes. It is
at first and become clear only after a predominantly basal, chronic men-
longer observation. ingitis. It occasionally affects the ver-
tex region and can lead to malre-
sorptive hydrocephalus.

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112 2 Diseases Mainly Affecting the Brain and its Coverings

| Cerebrovascular Syphilis (426) and enlarged, with a large post-

Cerebrovascular syphilis produces a voiding residual volume, but without
marked inflammation of the menin- pain. Impotence is another early
ges and cerebral blood vessels, lead- manifestation.
ing to infarction, usually in the distri-
bution of middle-sized arteries. In- Clinical Findings and Course
farction is preceded by prodromal Sensory abnormalities can always be
manifestations such as headache, found at the time of presentation. Vi-
personality change, dizziness, sleep bration sense and, later, position
disturbances and other nonspecific sense are either impaired or exagger-
symptoms. The vascular narrowing ated. Sensitivity to painful stimuli is
and parenchymal infarcts are re- lessened in deep and visceral struc-
vealed by imaging studies. The cere- tures (no pain on squeezing of the
brospinal fluid displays chronic in- testicle or Achilles tendon). Perineal
flammatory changes. pain sensation is delayed. The im-
pairment of position sense leads to
gait ataxia, which may be disabling,
| Tabes Dorsalis
in about one-third of patients. Ataxia
Tabes dorsalis arises on average
is particularly severe when the eyes
812 years after the primary infection
are closed or in darkness, and the
and is characterized by lancinating
tandem gait and Romberg test are
pain, ataxia, and bladder dysfunction.
abnormal. Involvement of muscle af-
Physical examination reveals hypo-
ferents in the posterior roots leads to
reflexia and abnormal pupillary reac-
hypotonia, which may be severe,
tions (Argyll Robertson pupil, p. 665).
causing abnormal mobility of the
Tabetic patients account for some
joints. The deep tendon reflexes dis-
30 % of patients with neurosyphilis.
appear in more than half of all pa-
Men are four to seven times more
tients, first the Achilles reflexes, and
commonly affected than women, in
then the patellar reflexes. Pyramidal
keeping with their higher rate of pri-
tract signs are rarely seen as well.
mary infection.
Sooner or later, 90 % of tabetics have
pupillary abnormalities. The pupils
Symptoms are usually unequal, constricted, and
Pain of sudden onset, lasting several misshapen and react to light weakly
seconds or minutes, and shooting or not at all. All transitional states are
(lancinating) into the legs or other found up to the classic Argyll Robert-
parts of the body is a characteristic son abnormality, which is seen in
early complaint. Painful tabetic crises some 20 % of tabetics. About the
are often felt in the epigastrium, rec- same number of patients suffer from
tum, penis, bladder, and elsewhere. optic atrophy, which usually leads to
Other common phenomena include blindness regardless of treatment.
paresthesias, sensory disturbances Oculomotor disturbances are rarer.
and associated gait difficulties Trophic manifestations include
(walking on cotton wool), as well as chronic perforating ulcer of the sole
ataxic gait. Bladder dysfunction often of the foot and tabetic arthropathy
appears early and is usually irrevers- with severe joint destruction (Char-
ible; the bladder is typically atonic cot joint).

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 Infectious Diseases of the Brain and Meninges 113

Neuropathology Optic atrophy, posterior column dys-

Thinning and sclerosis of the poste- function, and other signs of tabes dor-
rior columns of the spinal cord is ap- salis may be used, in which case the
preciable on gross examination. Mi- term taboparalysis is applied. Mal-
croscopically, a degeneration of fibers resoptive hydrocephalus is occasion-
entering via the posterior horn is ally seen (p. 39).
seen. The fibers of the posterior col-
umns are demyelinated, with spo- Mental Abnormalities
radic axonal degeneration, and gliosis These are often more prominent than
is present. the neurologic deficits. Most common
is a slowly progressive dementia with
| General Paresis (1046) memory loss, affective disturbances,
General paresis appears 1015 years impairment of judgment, and corre-
after the primary infection, and spondingly abnormal behavior lead-
sometimes even later. It is associated ing to social impairment. Less fre-
with a progressive dementia and is quently, the disturbance is of the hy-
the clinical correlate of a parenchy- perreactive or expansive type, in
mal meningoencephalitis with case- which the patient suffers from delu-
ating granulomatous inflammation sions of grandeur and may undertake
(gumma or gummata). Men are more fantastic exploits as a result. In the fi-
commonly affected than women. nal, paralytic stage, dysphasia, agno-
sia, and apraxia complete the picture
Clinical Features of dementia.
Progressive dementia is the most
prominent manifestation and is often Neuropathology
associated with lack of judgment, ex-
Gross examination reveals thickening
pansive features, epileptic seizures,
of the meninges, brain atrophy, ven-
dysarthria, pupillary dysfunction,
tricular enlargement, and granuloma-
myoclonus, and variable focal neuro-
tous ependymitis. Microscopically, a
logic signs.
subacute encephalitis is found, with
The initial symptoms are often non-
many inflammatory cells in the peri-
specific: headache, fatigability, and
vascular spaces and in the brain pa-
sleep disturbances. Some 10 % of pa-
renchyma itself. Neuronal loss and
tients go on to have seizures. In rare
glial proliferation are seen, and spiro-
cases, there are transient focal signs,
chetes can be detected with the use
such as hemiparesis. Pupillary dys-
of special stains.
function, as in tabes dorsalis, is char-
acteristic (p. 664), as is a slurred, syl-
labic form of dysarthria best brought Prognosis
out with certain test phrases General paresis usually leads to death
(around the rugged rocks the ragged within 3 years if untreated. Spontane-
rascal ran, hopping hippopotamus, ous improvement is rare.
Methodist Episcopal). Muscular
jerks known as sheet lightning may | Other Forms of Neurosyphilis
be seen, particularly around the The neurologic expression of syphilis
mouth. The reflexes are often brisk, is by no means limited to tabes dorsa-
and a Babinski sign is often present. lis and general paresis and may take

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114 2 Diseases Mainly Affecting the Brain and its Coverings

on many other forms, often mimick- well-demarcated contrast-enhancing

ing other neurologic diseases. Exam- masses. Cranial nerve and meningeal
ples include syphilitic optic atrophy, involvement may also be visible, par-
which leads to progressive blindness, ticularly on MRI (92, 942).
first in one eye, and then in the other;
and syphilitic sensorineural deafness. Treatment
For congenital syphilis, see p. 37. Patients with neurosyphilis, even if
asymptomatic, should be treated
Diagnosis of Neurosyphilis
with high-dose penicillin G (1224
The diagnosis is based on serology million units i.v. qd for 10 days), or
and on the cerebrospinal fluid exami- alternatively with ceftriaxone (1 g
nation. i.v. q.i.d. for 14 days).
As for serology, a number of nonspe- Successful treatment results in a
cific screening tests (such as the VDRL decline of the VDRL antibody titer,
test) and specific treponemal tests which should be rechecked at 1, 3,
(such as FTA-ABS and TPHA) are avail- 6, and 12 months after treatment.
able. The nonspecific tests are ade- Nonspecific tests for syphilis often
quate for routine testing of large become negative, but the specific
numbers of serum samples. Their re- tests do not. The cerebrospinal
sults are expressed as a quantitative fluid should be reexamined every
antibody titer, which provides infor- 36 months for 3 years to docu-
mation about the possible presence ment the expected fall in cell count
and activity of the syphilis-producing and somewhat slower fall of the el-
organisms. Specific tests are used to evated protein concentration.
confirm the diagnosis in patients
with positive nonspecific tests, or in
whom there is an elevated clinical | Borreliosis (330)
suspicion. The cerebrospinal fluid dis- Borrelia burgdorferi, afzelii, and garinii
plays the features of chronic meningi- are the etiological agents of the Euro-
tis (see Table 2.22). The most pro- pean Garin-Bujadoux-Bannwarth
nounced CSF changes, with the high- syndrome, and Borrelia burgdorferi
est cell counts, are found in syphilitic that of North American Lyme disease
meningitis, the least pronounced in (which takes its name from the town
tabes dorsalis. The CSF protein con- of Lyme, Connecticut). These organ-
centration rarely exceeds 200 mg/dL isms are spirochetes related to the
and is usually below 100 mg/dL. The treponemes that cause syphilis (159)
glucose concentration is normal or and are transmitted to human beings
mildly low. The CSF abnormalities are by tick bites. The initial infection is
very mild in some cases; rarely (usu- marked by local cutaneous erythema,
ally in cases of tabes dorsalis), the cell typically in the form of an enlarging
count is normal. CSF-specific oligo- ring (erythema chronicum migrans),
clonal bands are found in ca. 50 % of sometimes accompanied by flu-like
cases. Every patient with syphilis symptoms. Acute disseminated borre-
should also be tested for HIV, and vice liosis may appear very early, but
versa. chronic borreliosis may not be evident
Neuroimaging studies (CT, MRI) reveal until much later. The clinical picture
infarcts or gummata appearing as is so varied, and the rate of seroposi-

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 Infectious Diseases of the Brain and Meninges 115

tivity so high in the normal popula- cephalitis, and combinations of these

tion (1015 %), that practically every entities (Fig. 2.24).
manner of presentation of neurologic The most common form of neurologic
disease has been ascribed to borrelio- involvement is a lymphocytic menin-
sis in at least one case report (734). gitis with uni- or bilateral facial palsy
or radiculoneuritis. Uni- or multifocal
Clinical Features (595, 735) encephalitis or vasculitis is rarer. Ra-
The early stage of infection (stage I), diculoneuritis is typically very painful
in which the infection is still local, is and may dominate the clinical pic-
characterized by erythema chroni- ture. Within weeks of presentation,
cum migrans or, less commonly, by cardiac involvement may become ev-
cutaneous erythema with lymphohis- ident in the form of intracardiac con-
tiocytic infiltration. Such skin duction abnormalities or, more rarely,
changes are seen, however, in fewer myopericarditis with ventricular dys-
than 25 % of patients with borreliosis. function. In the chronic, generalized
The disseminated infection (stage II) stage of infection (stage III), arthral-
makes itself known with headache, gias (60 %) and cutaneous abnormali-
fever, musculoskeletal pain, arthral- ties (acrodermatitis chronica atrophi-
gias, and sometimes a generalized cans) are typical. Late-stage neuro-
lymphadenopathy. Multifocal ery- logic abnormalities include a mild,
thema may arise in this stage. 15 % of nonspecific encephalopathy with
patients with disseminated borrelio- mild memory loss and mood changes,
sis suffer from neurologic syndromes or else leukoencephalopathy with
including meningitis, cranial neuritis, spastic paraparesis and bladder dys-
radiculoneuritis, plexus neuritis, en- function.

Fig. 2.24 Cranial polyradiculitis in borreliosis, in a 38-year-old man. This axial T1-
weighted spin-echo image reveals contrast enhancement of the meninges and cranial
nerves, particularly well seen in the leptomeninges around the medulla and in the hypo-
glossal nerves bilaterally.

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