Infectious

Neuropathies

 Infectious neuropathies are heterogeneous neuropathies

with multiple causes
There is evidence of direct involvement of nerves by the
infective agent, from the immune reaction of the patient
or secondary to the toxicity of the drugs used during
treatment.
Inflammatory neuropathies follow infection of the
peripheral nervous system (pns) caused by viruses,
bacteria, or parasites
Nerve lesions can result from the inflammatory reaction
induced by the infective agent or from the immune
reaction of the host

Infection with retroviruses

Includes infection with HIV-1 and -2, the agents of AIDS, and the
human t-lymphotropic virus type 1 (HTLV-1), the agent of tropical
myeloneuropathy
Neuropathies in HIV infection
Nerve lesions remain silent in most cases
Minor alterations of the nerve action potentials or of nerve conduction
velocity in patients who do not present signs or symptoms of
neuropathy are not predictive of the occurrence of symptomatic
neuropathy
The incidence of disabling clinical neuropathy increases with
progression of the immune depression but remains difficult to establish
Symptomatic neuropathy affects an estimated 5% to 10% of patients
who are HIV infected

 A wide variety of neuropathies occurs in the course of HIV

infection, including Guillain-Barre syndrome (GBS), multifocal
neuropathy, meningo radiculo neuritis, acute uni- or bilateral
facial palsy, and pan dys autonomia.
All these manifestations can be associated with central nervous
system (CNS) involvement or with inflammatory myopathy

Inflammatory polyneuritis of the Guillain-Barre type

GBS can occur at the time of seroconversion to HIV
Mild to severe motor deficit is associated with high fever, diarrhea,
rash, adenopathy, and mono nucleosic syndrome
The CSF protein content is high and the cell count low, but the cell
content often is more elevated than in classical GBS
The outcome of these gbs-like syndromes is not different from
classical GBS
Relapsing forms are rare
Nerve biopsy specimens from patients who have hiv-related gbs-like
syndrome show the whole range of lesions seen in GBS, including
macrophage-mediated demyelination, mixed axonal and
demyelinating lesions, or predominantly axonal lesions
It is more pronounced in distal nerves than in non hiv-related GBS

Subacute multifocal neuropathy

Common pattern of neuropathy observed in patients who have HIV
before the onset of cellular immunosuppression
Sensory or sensorimotor deficit often predominates in the lower
limbs
Paresthesiae and spontaneous pain are common
They usually are bilateral but often predominate on one side or can
affect the territory of a nerve trunk or of a spinal root
They often progress over a few weeks, affecting the upper limbs
Cranial nerves, especially the facial nerves, can be affected
Examination shows sensorimotor deficit of peripheral origin often
associated with exaggerated tendon reflexes and sometimes
Babinskis sign
The outcome of these neuropathies usually is good.
Patients improve spontaneously or after treatment with
corticosteroids

Distal symmetric polyneuropathy

Distal symmetric neuropathies represent the most common type
of peripheral neuropathy in patients who have HIV, especially at
a late stage of the HIV infection
Both feet are affected simultaneously by painful sensations, often
of the burning type, associated with allodynia
Painful retraction of the calf muscles occurs.
Motor involvement usually is absent or moderate
Slight pyramidal tract involvement is common
The ankle reflexes are absent or decreased; the other tendon
reflexes often are exaggerated

Dysautonomia in HIV infection

Disabling autonomic manifestations,

including postural hypotension and syncopes,

paroxysmal arterial hypertension,
sphincter disturbances,
abnormal pupil reaction to light, and
abnormal sweating, are reported in patients who have HIV

occur in association with sensorimotor neuropathy

Cytomegalovirus neuropathy
Cytomegalovirus (CMV) neuropathy is a treatable neuropathy
that occurs at a late stage of immunodepression
CMV infection represents the most common viral opportunistic
infection in AIDS, affecting 15% to 35% of patients who have
AIDS
Its most common clinical manifestation is retinitis, with vision
loss that often is bilateral
Peripheral neuropathy often is associated with retinitis or with
symptomatic CMV infection of other organs (colitis or
pancreatitis)
In most cases, patients who have proved CMV neuropathy have
AIDS with opportunistic infections

 The different patterns of CMV neuropathy include

(1) The polyradiculopathic patterndwithin a few days or weeks, patients
develop a sensorimotor deficit of the lower spinal roots or a complete
cauda equina syndrome with sphincter disturbances, often associated
with signs of CNS involvement and general signs and symptoms
(2) The multifocal pattern, which may include symptomatic lesions of
spinal roots, nerve trunks, and sometimes cranial nerve involvement
(3) Both patterns of peripheral neuropathy, which may be associated in
the same patient
(4) Severe CNS manifestations, including necrotic myelitis and
encephalitis
(5) The CSF abnormalities that can be observed in this setting, which
include high protein content (more than 10 g/L in one of the authors
patients), pleocytosis with polymorphonuclear leucocytes reaction, and
decreased CSF glucose

Neuropathies in human T-lymphotropic virus type 1related

tropical myeloneuropathy
PN dysfunction has been noted in various studies
PN involvement is characterized by mild sensorimotor, bilateral,
deficit affecting distal lower limbs in association with sphincter
disturbances and spinal cord involvement
In some patients, predominantly motor deficit and pyramidal
tract involvement mimics amyotrophic lateral sclerosis
On nerve biopsy specimens, perineurial and perivascular
inflammatory infiltrates with moderate axon loss and mixture of
segmental demyelination and axonal degeneration can be
observed
Demyelination and irregularity of the myelin sheath occur

Leprous neuropathy
Clinical manifestations
Specific cutaneous lesions, including maculae and lepromae, reveal
the disease in half or more of the patients especially in the
polybacillar-lepromatous type
In the others, small areas of sensory loss, limited anhydrosis and
alopecia zones, paresis of some facial muscles, hypochromic or
atrophic cutaneous zones, or painful enlargement of a nerve trunk
are the presenting manifestations
Plantar ulcers and other trophic changes occur later in the course of
the disease, as a consequence of sensory loss
The large nerve trunks affected most commonly are the ulnar and
the lateral popliteal nerves, followed by the median, posterior tibial,
superficial radial, and peroneal nerves and the greater auricular and
facial nerves

Sensory loss
most constant finding of leprous neuropathy
result of mixed dermal nerve and nerve trunk damage
Early cutaneous lesions show some preservation of sensation, with
impairment of light touch and loss of thermal and pain sense while
preserving proprioception, so patients still can use their largely
anesthetic limbs effectively, which leads to painless trauma and
trophic changes
Loss of dermal pigment in the territory of affected cutaneous
nerves leads to development of large anesthetic patches in darkskinned people, with loss of sweating in corresponding area
In some cases, complete loss of pain and temperature sensations
in a certain area contrasts with preservation of tactile sensation
In most cases, all modalities of superficial sensations are affected
In cases of longstanding evolution, the distal part of the limbs show
the greatest sensory loss

Nerve hypertrophy
Nerve trunks are enlarged palpably in an estimated one third of
patients who have leprosy
Superficial nerves, such as the greater auricular nerve in the
neck, the supraorbitary branch of the trigeminal nerve or larger
nerve trunks (especially the ulnar nerve above the elbow), the
peroneal nerve, and the radial cutaneous nerve at the lateral
border of the wrist often are enlarged
Nerve hypertrophy sometimes is associated with spontaneous
tingling or with painful sensations.
Palpation of the nerve itself occasionally is painful

Motor disturbance and amyotrophy

Motor involvement usually is a late event in the course of the
disease
Amyotrophy and motor weakness usually progress pari passu;
in some cases however, amyotrophy is more marked than
weakness, both of which predominate in the ulnar and median
nerves territories, with characteristic claw hands
In the lower limbs, the peroneal nerve is affected predominantly
Motor involvement and amyotrophy usually progress slowly in an
approximately symmetric way
Facial palsy with lagophthalmos of one or both eyes, with sparing
of the other muscles supplied by the facial nerve, is a classical
feature of leprosy

Trophic disturbances
Trophic plantar ulcers is a common, nonspecific complication of
loss of pain sensation over the plantar sole
Plantar ulcer is subsequent to microtrauma on skin that has lost
painful sensation
The absence of protective sensation of limb extremities leads to
overuse, accidental self injury, recurrent infections, and gradual
development of further deformities as observed in sensory
neuropathy of different origin
Bone lesions, osteolysis, always are distally located, often are
bilateral gradually affecting the phalanges, metacarpal, and
metatarsal bones, causing deformities of the limbs
The process starts in the distal end of phalanges, destroys the
joint surfaces, and progresses without causing bone reaction

Diagnosis
Nerve biopsies are useful in the diagnosis and management of
leprosy.
nerve biopsy may be useful in differentiating leprous neuropathy
from neuropathy of other origin, including diabetic neuropathy,
hereditary sensory neuropathies, or amyloid neuropathy
Ziehls staining of paraffin embedded sections permits
visualization of bacilli in the pluribacillar forms of the disease

Treatment
Leprologists advised to treat patients who have paucibacillary
leprosy, which include the tuberculoid and borderline tuberculoid
forms, for 6 months only, with daily unsupervised dapsone (100
mg) and monthly supervised rifampicin (600 mg); all treatment
then stops and patients remain under observation for 2 years
Multibacillary patients require a minimum of 2 years treatment,
but should continue preferably until skin smears are negative;
they are treated with daily dapsone (100 mg) together with
clofamizine (300 mg), both supervised
On completion, multibacillary patients should remain under
observation for 5 years.

Lyme disease
Lyme disease is a multisystem illness that affects the skin, joints,
heart, and nervous system, caused by a tick-transmitted
spirochetae, Borrelia burgdorferi
Clinical manifestations
The course of the disease follows three stages
Stage 1: Typical patients first have erythema migrans, sometimes
followed several weeks or months later by meningitis or facial
palsy and, often, months later by arthritis.
It is accompanied by fever, minor constitutional symptoms, or
regional lymphadenopathy

 Stage 2: Within days or weeks after inoculation, the spirochete may

spread in patients blood to many sites and has been recovered from
blood during this stage and from many organs
By this time, the host starts to develop a strong immune response to
B burgdorferi antigens that result in destruction of spirochetes by
complement activation through immune complexes
After several weeks or months, 15% to 20% of patients develop
neurologic signs
The first neurologic sign usually is radicular pain, often of the
burning type, associated or not with weakness, with little or no
clinical signs of meningitis
Meningitis is the most common neurologic abnormality in Lyme
disease
Papilledema and increased CSF pressure can occur. CSF examination
reveals a lymphocytic pleocytosis

 Multifocal spinal root or cranial nerve involvement often develops

within a few days or weeks, with uni- or bilateral facial palsy and
asymmetric sensorimotor radiculoneuropathy
Facial palsy often is bilateral.
The cranial nerves can be affected, in association with
meningitis.
Cranial nerve palsies resolve within weeks or months, sometimes
incompletely
Sphincter disturbances occur
Cardiac involvement occurs in 4% to 8% of patients.
They include fluctuating atrioventricular node block, mildle rt
ventricular dysfunction, or, rarely, cardiomegaly or fatal
pancarditis

 Stage 3: Arthritis occurs by transient episodes, a mean of 6

months after the onset of the disease
characterized by asymmetric oligoarticular arthritis especially of
the knee; one or a few joints are affected
A variety of late syndromes affecting the CNS is described,
including spastic paraparesis, ataxia, relapsing multiple sclerosis
like illness, bladder dysfunction, cognitive impairment, dementia,
and subacute encephalitis
Diagnosis
From a neurologic point of view, presence of a subacute
meningoradiculoneuritis with facial palsy and signs and
symptoms suggesting a multifocal involvement of the PNS is
highly suggestive of Lyme borreliosis
Serology is the only practical laboratory aid in diagnosis

Treatment
Treatment with high doses of penicillin gives good results at stage
1, but the results are not as good in patients who have stage 2
neurologic abnormalities and in patients who have arthritis
B burgdorferi seems highly sensitive to tetracycline, ampicilline,
and ceftriaxone but only moderately sensitive to penicillin.
For early Lyme disease localized stage 1 or disseminated stage 2,
oral tetracycline generally is an effective antibiotic
Doxycycline, a long-acting tetracycline that achieves better tissue
levels, may be preferable. The treatment should be administered
for 10 to 30 days
ceftriaxone now is used commonly because it crosses the bloodbrain barrier more readily and requires only once-a-day
administration