104 2 Diseases Mainly Affecting the Brain and its Coverings
Treatment
Fig. 2.22 Progressive multifocal leu-
koencephalopathy.
A 75-year-old man with leukemia and corti-
cal blindness. The signal change in the
white matter is typical, as are the un-
changed signal intensity and thinning of
the adjacent gray matter (arrows).
Chronic Meningitis (955)
Chronic meningitis is diagnosed
when the clinical signs and symp-
toms of meningitis, including inflam-
matory changes of the cerebrospinal
fluid, persist for at least 4 weeks. The
various etiologies are summarized in
Table 2.29. Their frequency varies
highly in immune-competent and
immunocompromised patients (p.
120). Relevant aspects of the patients
history include earlier illnesses, oper-
ations and malignancies, travel, tick
bites, sexual behavior, and eating
habits.
Clinical Features
The most prominent manifestations
are headache, fever, and nuchal rigid-
ity, but these may be very mild, and
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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.
Decisions whether to give anticon-
vulsants or ulcer prophylaxis
should be made on an individual
basis.
other relevant physical findings or
suggestive history may be absent.
Occasionally, erythema chronicum
migrans will point to a diagnosis of
borreliosis (Lyme disease), or the fun-
duscopic examination will reveal
signs of chorioretinitis. Rarely (e.g., in
sarcoidosis), there may be signs of
hypothalamic or pituitary dysfunc-
tion. Cranial nerve deficits are found
more often in tuberculous, sarcoid,
luetic, fungal, and neoplastic menin-
gitis, all of which preferentially affect
the basilar meninges.
Diagnosis
A complete blood count, serum en-
zymes, antinuclear antibodies, serol-
ogy for HIV, syphilis, and cryptococ-
cus, and a chest roentgenogram
should be obtained in every patient.
Cutaneous lesions may point to the
correct diagnosis in borreliosis, sar-
 Infectious Diseases of the Brain and Meninges
Table 2.29 Common etiologies and differential diagnoses of chronic meningitis (after
272)
Infectious
> Bacterial and mycobacterial
> Fungal
> Spirochetal
> Parasitic
> Viral
Non-infectious
Differential diagnosis
coidosis, secondary syphilis, tubercu-
losis, or disseminated fungal infec-
tion. The cerebrospinal fluid exami-
nation should include cell count,
protein, glucose, Gram and Ziehl-
Neelsen stains, syphilis and Borrelia
serologies, a touch prep for the dem-
onstration of cryptococcus, and cytol-
ogy for the detection of neoplastic
cells (p. 79).
Further, the cerebrospinal fluid
should be cultured for aerobic and
anaerobic bacteria, fungi, and tuber-
cle bacilli. These tests should be per-
formed at least three times, both to
increase the diagnostic yield and to
assess the dynamics of the disease
over time.
A CT or, preferably, MRI scan may in-
dicate a lesion of the brain paren-
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105
Tuberculosis
Brucellosis
Cryptococcosis
Candidiasis
Coccidioidomycosis (in North America)
Histoplasmosis (in the United States)
Syphilis
Borreliosis (Lyme disease)
Cysticercosis
Echinococcosis
HIV
Neoplastic meninigitis
Sarcoidosis
Granulomatous vasculitis
Isolated CNS vasculitis
Systemic lupus erythematosus
Behcets disease
Vogt-Koyanagi-Harada syndrome
Parameningeal inflammatione.g., epidural abscess,
osteomyelitis
chyma (e.g., in cysticercosis, toxoplas-
mosis, and tuberculosis), and the
chronically inflamed meninges en-
hance with intravenously adminis-
tered contrast (see Fig. 2.15). Imaging
studies are also necessary to rule out
the presence of parameningeal foci of
infection, hydrocephalus complicat-
ing chronic basilar meningitis, and
multiple infarcts due to vasculitis.
Vasculitis can be ruled out by angiog-
raphy. Because chronic meningitis
may be the central nervous manifes-
tation of an infection involving other
organs as well, the lymph nodes, liver,
and bone marrow may need to be bi-
opsied, and the gastric juice, sputum
and urine may need to be cultured for
mycobacteria and other pathogens,
depending on the specific clinical
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-
sis remains unclear, the neuroradiolo-
gically visible changes in the menin-
ges or brain should be directly inves-
tigated by biopsy and culture. The
neurosurgeon should also take this
opportunity to obtain ventricular
fluid for culture (Table 2.30).
Recurrent Meningitis
The syndrome of recurrent aseptic
meningitis with symptom-free inter-
vals is known as Mollarets meningitis
(622). In a recent study, PCR analysis
demonstrated the presence of HSV-II
in patients cerebrospinal fluid dur-
ing, but not between, the meningitic
episodes; this illness is thus thought
to represent an initial infection with
HSV-II followed by one or more epi-
sodes of reactivation. It remains un-
clear whether virustatic therapy can
shorten the meningitic episodes. It
seems reasonable to treat frequently
recurring episodes with famciclovir,
500 mg p.o. b.i.d., for 10 days.

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 Infectious Diseases of the Brain and Meninges
Allergic reactions to medications,
usually nonsteroidal anti-inflam-
matory agents, can also produce re-
current meningitis (195). Further
causes include acquired or congenital
dural defects, epidermoid cyst, or a
parameningeal infection that repeat-
edly breaks into the subarachnoid
space.
Treatment
When chronic meningitis is due to
a known pathogenic organism, the
treatment is directed at its eradica-
tion. Usually, however, the etiology
is not yet known when a therapeu-
tic decision must be taken. When
borreliosis is suspected, ceftriaxone
can be given for 3 weeks. If the pa-
tients condition worsens despite
this treatment, tuberculostatic
treatment should be given without
hesitation. In such situations, a
possible fungal infection should be
sought by all available diagnostic
means, even while tuberculostatic
treatment is in progress, and, if dis-
covered, should be treated. If fungi
are not found, and if the level of
clinical suspicion for a fungal infec-
tion is not very high, then empiri-
cal antifungal therapy should not
be given, in view of its high toxicity.
Fungal Meningoencephalitis
The clinical features of fungal infec-
tion cover a broad spectrum (Table
2.31). The immune status of the pa-
tient is a crucial variable. Cryptococ-
cus neoformans is the most common
pathogen in the patient with normal
immune status, while Candida sp. and
Aspergillus sp. are more common in
the immunocompromised host. In
general, fungal illness plays a greater
role in arid geographic zones than
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107
Table 2.31 Types of fungal infection in
the CNS (after Bell and McGuinness, 80)
Meningitis (acute, subacute, chronic)
Granulomatous meningoencephalitis
Abscess (solitary, multiple, microabscess)
Granuloma (microgranuloma, mass le-
sion)
Infarct due to arterial or venous throm-
bosis
in Europe. Coccidioides immitis is
found only in the Americas, Histo-
plasma capsulatum worldwide but
with a particular concentration in the
Americas, and Blastomyces dermatiti-
dis in North America, Africa, and the
Middle East.
| Cryptococcosis
Cryptococcus neoformans mainly af-
fects patients with AIDS or other sys-
temic illnesses impairing the cellular
immune response (lymphoma, post-
transplantation, steroid therapy), and,
more rarely, patients with normal im-
mune status (231, 1050). The primary
infection occurs in the lungs. CNS in-
fection is usually subacute or chronic
and appears as a combination of
meningitis and multifocal granulo-
matous encephalitis (the clinical
signs of either of these two may pre-
dominate in individual cases). The
major symptom is headache, and as-
sociated signs of encephalitis include
personality changes, confusion, and
focal neurological deficits. In some
cases, a mild cognitive deficit is the
only manifestation of disease. The ce-
rebrospinal fluid examination usually
reveals a chronically inflammatory
picture (p. 84 and Table 2.22), which
may be only mild in the presence of
108 2 Diseases Mainly Affecting the Brain and its Coverings
Table 2.32 Fungi causing CNS infections,
in order of frequency (after Bell and
McGuinness, 80)
In patients with normal immune status:
> Cryptococcus neoformans
> Coccidioides immitis
> Histoplasma capsulatum
> Blastomyces dermatitidis
> Sporothrix schenckii
In the immunocompromised host:
> Candida spp.
> Aspergillus spp.
> Zygomycetes (Phycomycetes)
> Cryptococcus neoformans
> Histoplasma capsulatum
> Blastomyces dermatitidis
> Sporothrix schenckii
> Others
immunosuppression. The touch prep
directly reveals cryptococci in more
than half of all patients; when it does
not, the demonstration of anticrypto-
coccal antibodies in the serum and
cerebrospinal fluid is necessary for
rapid diagnosis. CSF cultures are posi-
tive by 46 weeks in three-quarters of
all patients. Blood, sputum, urine, and
stool cultures may also be helpful.
Treatment
The treatment consists of amphote-
ricin B and flucytosine. Immuno-
compromised patients require
long-term treatment with flucyto-
sine for the prevention of a relapse.
| Candidiasis (77)
Candidiasis is seldom restricted to
the central nervous system and gen-
erally is found in the CNS as a local
expression of systemic disease. It is
usually a consequence of visceral sur-
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gical procedures, intravenous cathe-
terization, steroid treatment, intrave-
nous drug use, and the like. It may
take an acute or chronic course, with
or without fever, and lead to menin-
gitis or meningoencephalitis, with
corresponding clinical features. The
cerebrospinal fluid examination usu-
ally reveals a chronically inflamma-
tory picture (see Table 2.21), with cell
count rarely above 2000/ L. The
diagnosis rests on the demonstration
of spores in the cerebrospinal fluid,
either directly or by culture.
Treatment
Candidiasis is treated with ampho-
tericin B and flucytosine.
Parasitic Diseases of the Brain
| Toxoplasmosis (542)
Toxoplasma gondii is an intracellular
parasite. Infection may be congenital,
or it may be acquired at any age
through the consumption of infected
meat or contact with the feces of do-
mestic animals or pets.
Congenital toxoplasmosis produces a
granulomatous meningoencephalitis
(p. 36).
Acquired toxoplasmosis is typically
asymptomatic or else a mono-
nucleosis-like illness with lymphade-
nopathy, fever, rash, myalgias, and
hepatosplenomegaly. In rare cases,
meningoencephalitis may be seen,
with up to 500 lymphocytes per mi-
croliter of cerebrospinal fluid (948).
Patients with AIDS or under pharma-
cological immunosuppression are at
increased risk of severe toxoplasmo-
sis infections, which may arise de
novo or as a reactivation of latent dis-
ease.
 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-
meters to 2 cm in size. Their clinical
manifestations are a function of their
size, number, localization, and stage
of development, together with the re-
action of the surrounding cerebral
tissue (833). They most commonly
cause epileptic seizures (224), head-
ache, papilledema, and vomiting, and
more rarely hydrocephalus, meningi-
tis, or spinal cord involvement.
CT and MRI are essential for the diag-
nosis (173) and reveal single or multi-
ple cystic lesions, sometimes contain-
ing radiologically identifiable larvae
(Fig. 2.23).
The dying cysticercus causes an in-
flammatory tissue reaction with
edema and then becomes calcified.
The cerebrospinal fluid may be nor-
mal or show chronic inflammation,
with eosinophils. The diagnosis is es-
tablished by serology or by direct
demonstration of cysticerci in biop-
sied tissue.
Treatment
Praziquantel and albendazole are
given in combination with cortico-
steroids (albendazole is more effec-
tive against neurocysticercosis
than praziquantel). Cysts must oc-
casionally be removed neurosur-
gically (190).
| Other Cestoid Infections
The larval form of other tapeworms
(cestodes) may cause infections in
man, including coenurosis, spargano-
sis, and echinococcosis.
Echinococcosis. This disease is caused
by the larvae of tapeworms for which
dogs and foxes are the definitive
hosts. Echinococcus granulosus gives
rise to solitary cysts, Echinococcus
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multilocularis to locally invasive cyst
agglomerates that are usually found
in the liver, lungs, and skeletal mus-
cle. The larvae may rarely stray into
the brain, where they form solitary
mass lesions that progress over sev-
eral months and cause epilepsy,
headache, papilledema, personality
changes, and focal neurologic deficits.
The diagnosis is made on the basis of
the neuroradiologic findings and se-
rology, which is usually, though not
always, positive.
Treatment
Cysts should be neurosurgically re-
sected whenever possible. If the
cyst is unresectable, albendazole
can be given.
| Nematoid Infections
Trichinosis is the most common ne-
matoid infection affecting man and is
usually contracted by the consump-
tion of undercooked pork. The in-
gested larvae spread through the
bloodstream to the soft tissues. After
an initial diarrheal phase, the disease
manifests itself by fever, prostration,
myalgias due to myositis, periorbital
edema, and, in 10 % of cases, meningi-
tis, encephalitis, or meningoencepha-
litis. Eosinophilia in the peripheral
blood is present, indicating a parasitic
infection. The diagnosis is established
by serology or muscle biopsy.
Treatment
Steroids (prednisone, 1 mg/kg, for
5 days) are effective against myosi-
tis, but antihelminthic agents are
ineffective against the larvae in the
soft tissues.
 Infectious Diseases of the Brain and Meninges
| Rickettsial Infections (1034)
Rickettsiae are intracellular parasites
that cause a number of illnesses in-
cluding Rocky Mountain spotted fe-
ver, louse-born typhus, Q fever, and
trench fever. These illnesses are
transmitted by ticks, lice, and fleas.
Central nervous system involvement
is indicated by the presence of head-
ache and other neurologic manifesta-
tions and may dominate the clinical
picture. Serologic tests are available
for most of the rickettsioses.
Treatment
Tetracycline and chloramphenicol
are the antimicrobial agents of first
choice.
Encephalopathies Caused by
Immune Reaction (469)
Certain infectious diseases and im-
munizations rarely provoke immune
reactions leading to complications in
the central nervous system. An in-
flammatory, demyelinating encepha-
lomyelitis typically arises days to
weeks after the infection or immuni-
zation, with a monophasic course.
Post-vaccinial and post-infectious en-
cephalomyelitides are most often
seen after rabies and measles immu-
nizations or after a measles infection
(p. 130), mumps, chickenpox, or ru-
bella (360).
Cerebrospinal fluid pleocytosis is
usually present, and MRI reveals mul-
tifocal signal changes (509). The dif-
ferential diagnosis between one of
these entities and the initial phase of
multiple sclerosis may be impossible
at first and become clear only after
longer observation.
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111
Spirochetal and Leptospiral
Infections
| Neurosyphilis (662, 1003)
Syphilis (lues) is a chronic, sexually
transmitted infection caused by the
spirochete Treponema pallidum. Its
three phases are known as primary,
secondary, and tertiary syphilis.
Syphilitic meningitis may occur as
early as the secondary phase, but typ-
ical neurosyphilis occurs in the ter-
tiary phase. Neurosyphilis may be
meningeal, meningovascular, or paren-
chymal; in the latter form, it is associ-
ated with the classical syndromes of
general paresis (earlier known as
general paresis of the insane) and
tabes dorsalis. If the patient is clini-
cally asymptomatic and serologic
tests are positive only in the blood,
then one speaks of seropositive latent
syphilis; if serologic tests are positive
in the cerebrospinal fluid as well, one
speaks of asymptomatic neurosyphi-
lis. Cerebrospinal fluid changes ap-
pear in one-third of all syphilitic in-
fections, usually between 12 and
18 months after the primary infec-
tion, at which time meningovascular
syphilis is also most frequent. General
paresis or tabes dorsalis appears
years or even decades after the pri-
mary infection in 7 % of all untreated
syphilitics.
| Meningeal Syphilis
Meningeal syphilis may affect the
meninges of either the brain or the
spinal cord and manifests itself as
headache, vomiting, meningism, cra-
nial nerve deficits, papillitis, seizures,
and occasionally mental changes. It is
a predominantly basal, chronic men-
ingitis. It occasionally affects the ver-
tex region and can lead to malre-
sorptive hydrocephalus.
112 2 Diseases Mainly Affecting the Brain and its Coverings
| Cerebrovascular Syphilis (426)
Cerebrovascular syphilis produces a
marked inflammation of the menin-
ges and cerebral blood vessels, lead-
ing to infarction, usually in the distri-
bution of middle-sized arteries. In-
farction is preceded by prodromal
manifestations such as headache,
personality change, dizziness, sleep
disturbances and other nonspecific
symptoms. The vascular narrowing
and parenchymal infarcts are re-
vealed by imaging studies. The cere-
brospinal fluid displays chronic in-
flammatory changes.
| Tabes Dorsalis
Tabes dorsalis arises on average
812 years after the primary infection
and is characterized by lancinating
pain, ataxia, and bladder dysfunction.
Physical examination reveals hypo-
reflexia and abnormal pupillary reac-
tions (Argyll Robertson pupil, p. 665).
Tabetic patients account for some
30 % of patients with neurosyphilis.
Men are four to seven times more
commonly affected than women, in
keeping with their higher rate of pri-
mary infection.
Symptoms
Pain of sudden onset, lasting several
seconds or minutes, and shooting
(lancinating) into the legs or other
parts of the body is a characteristic
early complaint. Painful tabetic crises
are often felt in the epigastrium, rec-
tum, penis, bladder, and elsewhere.
Other common phenomena include
paresthesias, sensory disturbances
and associated gait difficulties
(walking on cotton wool), as well as
ataxic gait. Bladder dysfunction often
appears early and is usually irrevers-
ible; the bladder is typically atonic
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and enlarged, with a large post-
voiding residual volume, but without
pain. Impotence is another early
manifestation.
Clinical Findings and Course
Sensory abnormalities can always be
found at the time of presentation. Vi-
bration sense and, later, position
sense are either impaired or exagger-
ated. Sensitivity to painful stimuli is
lessened in deep and visceral struc-
tures (no pain on squeezing of the
testicle or Achilles tendon). Perineal
pain sensation is delayed. The im-
pairment of position sense leads to
gait ataxia, which may be disabling,
in about one-third of patients. Ataxia
is particularly severe when the eyes
are closed or in darkness, and the
tandem gait and Romberg test are
abnormal. Involvement of muscle af-
ferents in the posterior roots leads to
hypotonia, which may be severe,
causing abnormal mobility of the
joints. The deep tendon reflexes dis-
appear in more than half of all pa-
tients, first the Achilles reflexes, and
then the patellar reflexes. Pyramidal
tract signs are rarely seen as well.
Sooner or later, 90 % of tabetics have
pupillary abnormalities. The pupils
are usually unequal, constricted, and
misshapen and react to light weakly
or not at all. All transitional states are
found up to the classic Argyll Robert-
son abnormality, which is seen in
some 20 % of tabetics. About the
same number of patients suffer from
optic atrophy, which usually leads to
blindness regardless of treatment.
Oculomotor disturbances are rarer.
Trophic manifestations include
chronic perforating ulcer of the sole
of the foot and tabetic arthropathy
with severe joint destruction (Char-
cot joint).
 Infectious Diseases of the Brain and Meninges
Neuropathology
Thinning and sclerosis of the poste-
rior columns of the spinal cord is ap-
preciable on gross examination. Mi-
croscopically, a degeneration of fibers
entering via the posterior horn is
seen. The fibers of the posterior col-
umns are demyelinated, with spo-
radic axonal degeneration, and gliosis
is present.
| General Paresis (1046)
General paresis appears 1015 years
after the primary infection, and
sometimes even later. It is associated
with a progressive dementia and is
the clinical correlate of a parenchy-
mal meningoencephalitis with case-
ating granulomatous inflammation
(gumma or gummata). Men are more
commonly affected than women.
Clinical Features
Progressive dementia is the most
prominent manifestation and is often
associated with lack of judgment, ex-
pansive features, epileptic seizures,
dysarthria, pupillary dysfunction,
myoclonus, and variable focal neuro-
logic signs.
The initial symptoms are often non-
specific: headache, fatigability, and
sleep disturbances. Some 10 % of pa-
tients go on to have seizures. In rare
cases, there are transient focal signs,
such as hemiparesis. Pupillary dys-
function, as in tabes dorsalis, is char-
acteristic (p. 664), as is a slurred, syl-
labic form of dysarthria best brought
out with certain test phrases
(around the rugged rocks the ragged
rascal ran, hopping hippopotamus,
Methodist Episcopal). Muscular
jerks known as sheet lightning may
be seen, particularly around the
mouth. The reflexes are often brisk,
and a Babinski sign is often present.
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113
Optic atrophy, posterior column dys-
function, and other signs of tabes dor-
salis may be used, in which case the
term taboparalysis is applied. Mal-
resoptive hydrocephalus is occasion-
ally seen (p. 39).
Mental Abnormalities
These are often more prominent than
the neurologic deficits. Most common
is a slowly progressive dementia with
memory loss, affective disturbances,
impairment of judgment, and corre-
spondingly abnormal behavior lead-
ing to social impairment. Less fre-
quently, the disturbance is of the hy-
perreactive or expansive type, in
which the patient suffers from delu-
sions of grandeur and may undertake
fantastic exploits as a result. In the fi-
nal, paralytic stage, dysphasia, agno-
sia, and apraxia complete the picture
of dementia.
Neuropathology
Gross examination reveals thickening
of the meninges, brain atrophy, ven-
tricular enlargement, and granuloma-
tous ependymitis. Microscopically, a
subacute encephalitis is found, with
many inflammatory cells in the peri-
vascular spaces and in the brain pa-
renchyma itself. Neuronal loss and
glial proliferation are seen, and spiro-
chetes can be detected with the use
of special stains.
Prognosis
General paresis usually leads to death
within 3 years if untreated. Spontane-
ous improvement is rare.
| Other Forms of Neurosyphilis
The neurologic expression of syphilis
is by no means limited to tabes dorsa-
lis and general paresis and may take
114 2 Diseases Mainly Affecting the Brain and its Coverings
on many other forms, often mimick-
ing other neurologic diseases. Exam-
ples include syphilitic optic atrophy,
which leads to progressive blindness,
first in one eye, and then in the other;
and syphilitic sensorineural deafness.
For congenital syphilis, see p. 37.
Diagnosis of Neurosyphilis
The diagnosis is based on serology
and on the cerebrospinal fluid exami-
nation.
As for serology, a number of nonspe-
cific screening tests (such as the VDRL
test) and specific treponemal tests
(such as FTA-ABS and TPHA) are avail-
able. The nonspecific tests are ade-
quate for routine testing of large
numbers of serum samples. Their re-
sults are expressed as a quantitative
antibody titer, which provides infor-
mation about the possible presence
and activity of the syphilis-producing
organisms. Specific tests are used to
confirm the diagnosis in patients
with positive nonspecific tests, or in
whom there is an elevated clinical
suspicion. The cerebrospinal fluid dis-
plays the features of chronic meningi-
tis (see Table 2.22). The most pro-
nounced CSF changes, with the high-
est cell counts, are found in syphilitic
meningitis, the least pronounced in
tabes dorsalis. The CSF protein con-
centration rarely exceeds 200 mg/dL
and is usually below 100 mg/dL. The
glucose concentration is normal or
mildly low. The CSF abnormalities are
very mild in some cases; rarely (usu-
ally in cases of tabes dorsalis), the cell
count is normal. CSF-specific oligo-
clonal bands are found in ca. 50 % of
cases. Every patient with syphilis
should also be tested for HIV, and vice
versa.
Neuroimaging studies (CT, MRI) reveal
infarcts or gummata appearing as
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well-demarcated contrast-enhancing
masses. Cranial nerve and meningeal
involvement may also be visible, par-
ticularly on MRI (92, 942).
Treatment
Patients with neurosyphilis, even if
asymptomatic, should be treated
with high-dose penicillin G (1224
million units i.v. qd for 10 days), or
alternatively with ceftriaxone (1 g
i.v. q.i.d. for 14 days).
Successful treatment results in a
decline of the VDRL antibody titer,
which should be rechecked at 1, 3,
6, and 12 months after treatment.
Nonspecific tests for syphilis often
become negative, but the specific
tests do not. The cerebrospinal
fluid should be reexamined every
36 months for 3 years to docu-
ment the expected fall in cell count
and somewhat slower fall of the el-
evated protein concentration.
| Borreliosis (330)
Borrelia burgdorferi, afzelii, and garinii
are the etiological agents of the Euro-
pean Garin-Bujadoux-Bannwarth
syndrome, and Borrelia burgdorferi
that of North American Lyme disease
(which takes its name from the town
of Lyme, Connecticut). These organ-
isms are spirochetes related to the
treponemes that cause syphilis (159)
and are transmitted to human beings
by tick bites. The initial infection is
marked by local cutaneous erythema,
typically in the form of an enlarging
ring (erythema chronicum migrans),
sometimes accompanied by flu-like
symptoms. Acute disseminated borre-
liosis may appear very early, but
chronic borreliosis may not be evident
until much later. The clinical picture
is so varied, and the rate of seroposi-
 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
manner of presentation of neurologic
disease has been ascribed to borrelio-
sis in at least one case report (734).
Clinical Features (595, 735)
The early stage of infection (stage I),
in which the infection is still local, is
characterized by erythema chroni-
cum migrans or, less commonly, by
cutaneous erythema with lymphohis-
tiocytic infiltration. Such skin
changes are seen, however, in fewer
than 25 % of patients with borreliosis.
The disseminated infection (stage II)
makes itself known with headache,
fever, musculoskeletal pain, arthral-
gias, and sometimes a generalized
lymphadenopathy. Multifocal ery-
thema may arise in this stage. 15 % of
patients with disseminated borrelio-
sis suffer from neurologic syndromes
including meningitis, cranial neuritis,
radiculoneuritis, plexus neuritis, en-
entities (Fig. 2.24).
The most common form of neurologic
involvement is a lymphocytic menin-
gitis with uni- or bilateral facial palsy
or radiculoneuritis. Uni- or multifocal
encephalitis or vasculitis is rarer. Ra-
diculoneuritis is typically very painful
and may dominate the clinical pic-
ture. Within weeks of presentation,
cardiac involvement may become ev-
ident in the form of intracardiac con-
duction abnormalities or, more rarely,
myopericarditis with ventricular dys-
function. In the chronic, generalized
stage of infection (stage III), arthral-
gias (60 %) and cutaneous abnormali-
ties (acrodermatitis chronica atrophi-
cans) are typical. Late-stage neuro-
logic abnormalities include a mild,
nonspecific encephalopathy with
mild memory loss and mood changes,
or else leukoencephalopathy with
spastic paraparesis and bladder dys-
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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