Transcript PERIPHERAL NEUROPATHY

Neurocysticercosis
Mehila Z.
March 19th 2007
Introduction Cysticercosis
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Cysticercosis is a systemic illness caused by disseminated
larval form of pork tapeworm, Taenia solium.
Encystment of larvae can occur in almost any tissue.
Involvement of the central nervous system, known as
neurocysticercosis (NCC), is the most clinically important
manifestation of the disease.
Introduction Neurocysticercosis
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Most common helminthic disease of the nervous system.
Common in Latin America, Asia, sub-Saharan Africa,
India, and east Asia as well as in industrialized nations
with a high immigration rate.
50 million people worldwide.
In endemic regions, leading cause of hospital admissions
and the major cause of acquired epilepsy.
Affect men and women equally. Inflammation around
parasites may be more severe in women than in men.
Etiopathogenesis
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The adult tapeworm resides in the upper jejunum.
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The scolex attaches by both sucking disks and two rows of hooklets.
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Often 1 adult worm is present, which may live for years.
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usually about 3 m long, as many as 1000 proglottids, each of which
produces up to 50,000 eggs.
three to five proglottids are generally excreted into the feces,& the eggs
in these proglottids are infective for both humans and animals.
The eggs may survive in the environment for several months.
Kingdom: Animalia
Phylum: Platyhelminthes
Class: Cestoda
Order: Cyclophyllidea
Family: Taeniidae
Genus: Taenia
Species: T. solium
Etiopathogenesis
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Humans = definitive hosts.
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Pigs are intermediate hosts
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(Taeniasis), without symptoms.
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Intermittent fecal shedding.
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Embryos penetrate the GI mucosa of the pig (cysticerci).
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When undercooked pork is consumed, intestinal tapeworm will
again be formed, completing the life cycle
Within 60 to 90 days, the encysted larval stage develops.
Etiopathogenesis
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Human cysticercosis occurs when T solium eggs are
ingested via fecal-oral transmission from a tapeworm
host.
The human then becomes an accidental intermediate
host, with development of cysticerci within organs.
Cysticerci may be found in almost any tissue. The most
frequently reported locations are skin, skeletal muscle,
heart, eye, and most importantly, the CNS (NCC).
Etiopathogenesis
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Autoinfection.
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Fecal-oral autoinoculation.
Regurgitation of proglottids into the stomach.
Only 5 - 40 % of patients with cysticercosis have an adult worm in
their intestine.
Most individuals with intestinal tapeworm infection do not develop
symptomatic cysticercosis.
Cysticerci are liquid-filled vesicles consisting of a membranous wall
and a nodule containing the invaginated scolex. The scolex has a
head armed with suckers and hooks and a rudimentary body.
Stages Of Cysticercosis
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Three stages of development.
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Vesicular phase,
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Colloidal-granular stage,
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Parasite is a cyst with thin membrane liquid filled, transparent.
Can remain for decades in this stage.
Or degenerate that ends up with the death of the parasite.
Vesicular liquid becomes viscous and cloudy,
Wall and scolex is transformed granular structure.
No longer is viable.
Nodular calcified stage,
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Parasite becomes a calcified.
Vesicular
Vesicular-colloidal
Granular
Calcific
colloidal
Clinical Features Cysticercosis
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Clinical syndromes of cysticercosis.
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Neurocysticercosis (NCC).
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Extra-neural manifestations.
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Parenchymal.
Extra-parenchymal.
 Intra-ventricular.
 Subarachnoid.
 Spinal involvement.
Eye.
Muscle.
Subcutaneous tissue.
Oncospheres actively migrate Vs enter tissues
passively during high blood flow.
Diagnostic Criteria
Adapted from Del Brutto et al.
Absolute criteria:
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(Cysticercosis)
(Proposed diagnostic criteria for neurocysticercosis. Neurology 2001; 57:177–183)
Histological demonstration of the parasite,
cystic lesions showing the scolex on CT or MRI,
direct visualization of ocular parasites by fundoscopic examination
Major criteria:
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Lesions highly suggestive of neuro-cysticercosis on neuro-imaging,
positive serum enzyme-linked immunoblot for anti-cysticercal antibodies,
resolution of cysts after therapy after anti-parasitic therapy,
spontaneous resolution of small single enhancing lesions
Minor criteria:
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Lesions compatible with neurocysticercosis on neuroimaging,
clinical manifestations suggestive of neurocysticercosis,
positive CSF ELISA for anti-cysticercal antibodies or cysticercal antigens,
cysticercosis outside the CNS
Epidemiologic criteria:
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Definitive diagnosis:
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Evidence of a household contact with Taenia solium infection,
individuals coming from or living in an area where cysticercosis is endemic,
history of frequent travel to disease-endemic areas.
one absolute criterion or two major plus one minor and one epidemiologic criterion
Probable diagnosis:
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one major plus two minor criteria,
one major plus one minor and one epidemiologic criterion,
or three minor plus one epidemiologic criterion.
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Multiple subcutaneous nodules on the chest wall
and a few calcified lesions on chest X-ray
A 42-year-old man admitted at Nelson Mandela Academic Hospital (Umtata) South Africa presented with a
history of recurrent generalized tonic-clonic epileptic seizures of six years duration, disseminated nodules all
over the body of two-year duration and headache.
Clinical Features
Neurocysticercosis
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Many patients are asymptomatic.(80%).
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Inflammatory response develops around a
degenerating cysticercus.
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It is not known what triggers this degeneration.
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Peak presentation occur three to five years after
infection, but it can be delayed for >30 years.
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Sub acute to chronic onset, (except seizures).
Clinical Features
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Parenchymal cyst
Calcific cyst
Cysticercal encephalitis
Sub-arachnoid cyst
Racemose cyst
Ventricular cysts
Spinal cyst
Other forms
Clinical Features
Parenchymal cysts
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29-62% percent
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cerebral cortex or basal ganglia.
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usually <1 cm in diameter but can be much larger.
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frequently seizures, 50 to 80 percent of patients
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The risk of epilepsy in sero-positive individuals is two to
three times higher than in sero-negative controls
Clinical Features
Parenchymal cysts
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The seizures may be focal or generalized
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Neurologic examinations are usually normal,
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focal neurologic signs may be present.
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Severe headaches, rarely fever or signs of meningeal
irritation.
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Symptoms of increased ICP.
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Intellectual deterioration and psychiatric presentations
also occur.
Clinical Features
Calcific Cysts
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Clinically active. Seizures and focal neurologic symptoms
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Periodic or episodic peri-lesional edema
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May be associated with severe symptoms including
seizures and focal neurologic deficits
Clinical Features
Cysticercal Encephalitis
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Massive cysts in the brain parenchyma,
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An intense immune reaction can occur,
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Encephalitis and diffuse brain edema.
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Fever, headache, and hydrocephalus, with vomiting, impaired
consciousness, reduced visual acuity, and seizures.
Spontaneously, or provoked by therapy that causes a
large number of cysts to degenerate.
This presentation is most common in children and young
females for unknown reasons.
Clinical Features
Subarachnoid Cysts
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27-56%
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Cysticerci that lodge in the sub-arachnoid space may grow to 10 cm or
more since they are not limited by pressure from the brain parenchyma.
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Meningeal inflammation and abnormal thickening of the leptomeninges
at the base of the brain can result, which can lead to entrapment of the
cranial nerves manifest as visual field defects and cranial nerve palsies.
Hydrocephalus can also develop from arachnoiditis and secondary
occlusion of the foramen of Luschka or Magendie.
Inflammation can also involve the walls of blood vessels, leading to a
proliferative angiitis and vascular obstruction with secondary cerebral
infarcts. Focal neurologic motor signs, ataxia, and sensory dysfunction
can result, and this presentation tends to be associated with a relatively
poor prognosis.
Clinical Features
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Racemose Cysticercosis
Is characterized by proliferating lobulated cysts without
scolices,
Usually found in the ventricular system and sub-arachnoid
space.
These cysticerci undergo disproportionate growth of their
membrane, with extensions of membranes that group in
clusters resembling bunches of grapes.
Infrequent, but the most serious; associated with
arachnoiditis, basilar meningitis and hydrocephalus.
Clinical Features
Ventricular Cysts
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Floating freely or attached to the choroid plexus.
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10 to 20 percent of patients.
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Inflammatory responses > granular ependymitis >
obstructive hydrocephalus and raised intracranial pressure
of gradual or acute.
Associated symptoms; seizures, focal neurologic signs or
dementia.
Mobile cysts in the forth ventricle > intermittent obstruction
> leading to episodes of sudden loss of consciousness
related to head movements (Bruns' syndrome).
Clinical Features
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Spinal cysticercosis
1 to 3 percent of cases of NCC.
Intra-medullary or in the sub-arachnoid space. Extramedullary more common.
Lesions in the thoracic segments are most common.
Inflammatory & demyelinating changes in the peripheral
nerve roots.
Patients typically present with radicular pain or
paresthesias and may also have sphincter disturbances.
Cysticercosis at other sites
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Occular
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1-3% often asymptomatic
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Sub-retinal space or vitreous humor
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exclude by a proper ophthalmologic examination in all patients
with NCC prior to initiating therapy
Inflammation around degenerating cysticerci threatens vision
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chorioretinitis,
retinal detachment
vasculitis.
Cysticercosis at other sites
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Subcutaneous and intramuscular cysticercosis
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almost any body site,
muscle(10%), subcutaneous tissues(75%).
usually asymptomatic, subcutaneous pea-like nodule.
more common in patients from Asia & Africa than from Latin America.
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heavy muscle involvement > acute myopathy
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SC calcification can be detected incidentally with routine X-rays
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Cysts in the heart may be asymptomatic or may result in
arrhythmias and/or conduction abnormalities
In general
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History
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Asymptomatic
Epilepsy
Headache
Intracranial HTN
Stroke
Neuro-psychiatric
Hydrocephalus
Others
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Intra-sellar
Spinal
Ocular
systemic
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Physical examination
Cognitive decline
Dysarthria
Extra-ocular movement palsy
or paresis
Hemiparesis or hemiplegia,
which may be related to
stroke, or Todd paralysis
Hemi-sensory loss
Movement disorders
Hyper/hypo-reflexia
Gait disturbances
Meningeal signs
Diagnosis
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Extent of work-up depend on clinical presentation.
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Incidental finding during unrelated reasons,
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Seizures or neurologic symptoms, further investigation.
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Routine lab tests
Imaging
Serology
CSF examination
Pathology
Others
Criteria
Diagnosis
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Routine lab tests.
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Non specific CBC and liver function tests.
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Moderate eosinophilia is occasionally present.
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Stool examinations eggs are typically not found.
Plain x-ray.
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SC nodules.
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IC calcification.
Diagnosis
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CT/MRI.
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Nonspecific, other brain lesions, abscess or
malignancies.
Pathognomonic lesion = scolex identified as a mural
nodule within the cyst.
MRI preferred over CT.
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Sensitive in detecting small lesions,
Brainstem or intra-ventricular lesions,
Better for visualizing the scolex.
Diagnosis
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Serology.
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Anti-cysticercal antibodies/ cysticercal antigens.
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ELISA, crude or partially purified antigens, frequently
cross-reacted with other helminthic antibodies.
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75 percent sensitivity.
EITB, (enzyme-linked immunoelectrotransfer blot
assay), uses affinity-purified glycoprotein antigens.
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Sensitivity and specificity of 100 and 98 percent.
Sensitivity of the EITB falls to <70 % with inactive calcified
lesions or a single cerebral lesion.
Serum or CSF, higher sensitivity on serum.
Antibodies can persist for years after the death of parasites,
Diagnosis
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Serology.
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Antigen testing.
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Detect live parasites.
Monitoring patients following therapy.
Parasite antigen levels typically fall by three
months after successful treatment.
Diagnosis
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CSF examinations.
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Helpful.
Raised intracranial pressure.
Normal glucose, mildly elevated protein & white cell.
Sometimes the CSF white cells are predominantly
eosinophils.
However, the degree of abnormality in the CSF
depends upon whether cysts are adjacent to or have
contact with the sub-arachnoid space.
Serologic testing for anti-cysticercal antibodies or
parasite antigens can also be performed.
Diagnosis
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Pathology.
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A single brain lesion with no characteristic scolex.
Negative serology.
Epidemiology.
Cyst location.
Skin or muscle lesion.
The cysticercus will appear as.
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A white fluid-filled bladder about 5 to 10 mm in
diameter.
Containing a solid 2 mm long larval tapeworm scolex.
Macroscopic Pathology
Macroscopic aspect of parenchymatous cysticercus in diverse evolutionary
stages: vesicular cysts (straight arrow), colloidal cysts (curved arrow),
granulomas (arrow head) and calcifications (open arrow).
Microscopic Pathology
Diagnosis
Adapted from Del Brutto et al.
(Proposed diagnostic
criteria for neurocysticercosis. Neurology 2001; 57:177–183)
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PCR not yet available.
Diagnostic criteria.
Absolute criteria:
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Major criteria:
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Evidence of a household contact with Taenia solium infection,
Individuals coming from or living in an area where cysticercosis is endemic,
History of frequent travel to disease-endemic areas.
Definitive diagnosis:
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Lesions compatible with neuro-cysticercosis on neuroimaging,
Clinical manifestations suggestive of neuro-cysticercosis,
Positive CSF ELISA for anti-cysticercal antibodies or cysticercal antigens,
cysticercosis outside the CNS.
Epidemiologic criteria:
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Lesions highly suggestive of neuro-cysticercosis on neuro-imaging,
Positive serum enzyme-linked immunoblot for anti-cysticercal antibodies,
Resolution of cysts after therapy after anti-parasitic therapy,
Spontaneous resolution of small single enhancing lesions.
Minor criteria:
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Histological demonstration of the parasite,
Cystic lesions showing the scolex on CT or MRI,
Direct visualization of ocular parasites by fundoscopic examination.
One absolute criterion or two major plus one minor and one epidemiologic criterion.
Probable diagnosis:
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One major plus two minor criteria,
One major plus one minor and one epidemiologic criterion,
Or three minor plus one epidemiologic criterion.
Absolute Criteria
Hooks(open arrow) and the spiral canal (small arrows)
Funduscopic visualization of a sub-retinal cyst
Cystic lesions showing the scolex on neuro-imaging
Massive non-encephalitic
neurocysticercosis. Cysticercosis
Working Group in Peru.
Diagnosis
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PCR not yet available.
Diagnostic criteria.
Absolute criteria:
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Major criteria:
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Evidence of a household contact with Taenia solium infection,
Individuals coming from or living in an area where cysticercosis is endemic,
History of frequent travel to disease-endemic areas.
Definitive diagnosis:
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Lesions compatible with neuro-cysticercosis on neuroimaging,
Clinical manifestations suggestive of neuro-cysticercosis,
Positive CSF ELISA for anti-cysticercal antibodies or cysticercal antigens,
cysticercosis outside the CNS.
Epidemiologic criteria:
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Lesions highly suggestive of neuro-cysticercosis on neuro-imaging,
Positive serum enzyme-linked immunoblot for anti-cysticercal antibodies,
Resolution of cysts after therapy after anti-parasitic therapy,
Spontaneous resolution of small single enhancing lesions.
Minor criteria:
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Histological demonstration of the parasite,
Cystic lesions showing the scolex on CT or MRI,
Direct visualization of ocular parasites by fundoscopic examination.
One absolute criterion or two major plus one minor and one epidemiologic criterion.
Probable diagnosis:
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One major plus two minor criteria,
One major plus one minor and one epidemiologic criterion,
Or three minor plus one epidemiologic criterion.
Major Criteria
Lesions highly suggestive of NCC on neuro-imaging studies,
including: sub-arachnoid racemose cysts (A), enhancing lesions (B),
and parenchymal brain calcifications
CT before (left, top and bottom), 1 month (center, top, and bottom), and 3 months after (right, top and
bottom) a 1-week course of albendazole. Note the resolution of parenchymal brain cysticerci as the
result of therapy.
Contrast-enhanced MRI (A) showing a small single enhancing
lesion corresponding to a colloidal cysticercus. Control MRI (B) was
taken 16 weeks after showed spontaneous resolution of the lesion.
Diagnosis
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PCR not yet available.
Diagnostic criteria.
Absolute criteria:
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Major criteria:
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Evidence of a household contact with Taenia solium infection,
Individuals coming from or living in an area where cysticercosis is endemic,
History of frequent travel to disease-endemic areas.
Definitive diagnosis:
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Lesions compatible with neuro-cysticercosis on neuroimaging,
Clinical manifestations suggestive of neuro-cysticercosis,
Positive CSF ELISA for anti-cysticercal antibodies or cysticercal antigens,
cysticercosis outside the CNS.
Epidemiologic criteria:
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Lesions highly suggestive of neuro-cysticercosis on neuro-imaging,
Positive serum enzyme-linked immunoblot for anti-cysticercal antibodies,
Resolution of cysts after therapy after anti-parasitic therapy,
Spontaneous resolution of small single enhancing lesions.
Minor criteria:
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Histological demonstration of the parasite,
Cystic lesions showing the scolex on CT or MRI,
Direct visualization of ocular parasites by fundoscopic examination.
One absolute criterion or two major plus one minor and one epidemiologic criterion.
Probable diagnosis:
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One major plus two minor criteria,
One major plus one minor and one epidemiologic criterion,
Or three minor plus one epidemiologic criterion.
Minor Criteria
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Lesions compatible with NCC on neuro-imaging studies, hydrocephalus
(A), and multiple filling defect in the column of contrast material in a
myelogram (B)
Treatment
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Intestinal T. solium
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Praziquantel is first line treatment for all tapeworm
infections
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5 to 10 mg/kg in a single dose is administered for taeniasis (T.
saginata and T. solium) and diphyllobothriasis;
Efficacy is >95 percent.
Niclosamide an alternative for Taeniasis & other
tapeworms.
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The recommended dose
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Is 4 tablets in a single dose (2 g) for adults,
2 tablets (1 g) for children 11 to 34 kg,
And 3 tablets (1.5 g) for children >34 kg.
Niclosamide is no longer available in the united states.
Current consensus guidelines for treatment of neurocysticercosis.
Clin Microbiol Rev 2002 Oct;15(4):747-56.
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A panel of experts recommendations :
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(i) individualize therapeutic decisions, including whether to use
anti-parasitic drugs, based on the number, location, and viability of
the parasites within the nervous system;
(ii) actively manage growing cysticerci either with anti-parasitic
drugs or surgical excision;
(iii) prioritize the management of intracranial hypertension
secondary to neurocysticercosis before considering any other form
of therapy;
(iv) manage seizures as done for seizures due to other causes of
secondary seizures (remote symptomatic seizures) because they
are due to an organic focus that has been present for a long time.
Treatment
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Therapy should be individualized according
to the form of NCC
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Cysticidal drugs, (Praziquantel, albendazole)
Symptomatic drugs, (anticonvulsants, steroids)
Surgical resection of lesions,
Placement of ventricular shunts
Treatment
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Anthelminthic/ Cysticidal therapy.
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Therapy? Which agent? And in whom?
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Praziquantel and albendazole.
Treatment
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If the parasite is dead,
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Treatment is directed primarily against the symptoms
(e.g., Anticonvulsants for management of seizures).
If the parasite is viable or active
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Patient has vasculitis, arachnoiditis, or encephalitis,
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A course of steroids or immuno-suppressants is
recommended before the use of anti-cysticercal drugs.
If only parenchymal, subarachnoid, or spinal cysts
are present without the complications mentioned,
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Anti-cysticercal treatment can be considered, with the
concomitant use of steroids, even in patients with massive
brain infection.
Treatment
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Praziquantel.
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Synthetic heterocyclic isoquinolone-pyrazine derivative.
50 mg/kg/d for 15 days, but recommended dosages have
ranged from 10 to 100 mg/kg for 3 to 21 days. It has also been
suggested that exposing cysticerci to high concentrations of
praziquantel by giving three doses of 25 to 30 mg/kg at 2-hour
intervals might be sufficient to destroy the parasites.
50 mg/kg per day for 15 days causes the disappearance of 60 to
70 percent of these cysts three months after administration.
It does not cross the blood-brain barrier well, so CSF levels are
only approximately 20 percent of plasma levels.
The cytochrome P-450 hepatic metabolism of praziquantel is
induced by corticosteroids, phenytoin and phenobarbital. Thus,
serum levels of praziquantel are lowered.
Treatment
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Albendazole
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It does not interact with anticonvulsant medications, and reports
suggest coadministration of prednisolone has no adverse effect
on albendazole levels
Albendazole was initially administered at doses of 15 mg/kg/d
during 1 month. Further studies showed that at similar doses,
the length of therapy could be shortened to 1 week without
lessening the efficacy of the drug.
15 mg/kg per day [usually 800 mg/day in divided doses] for 15
days results in the destruction of 75 to 90 percent of
parenchymal brain cysts
More recent studies have shown that eight days of albendazole
therapy is equally as effective as 15 days. It is possible that
even a three-day course of albendazole may be sufficient, but
these studies are ongoing
Consequently, praziquantel is generally considered to be secondline therapy behind albendazole
Treatment
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Anticonvulsant therapy.
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Indication: seizures or high risk.
Carbamazepine or phenytoin can be used.
Duration of treatment not settled.
Highest risk: degenerating lesions and inflammation.
The disappearance of cysts = better epilepsy control.
Not been proven.
Calcified and inactive lesions = focus for seizures.
The current practice in most situations is to continue
anticonvulsant therapy for one year (sometimes two)
and then stop if a patient has remained seizure-free.
Treatment
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Corticosteroids.
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Are the primary form of therapy for.
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Corticosteroids must be administered before, during, and even
some days after the course of cysticidal drugs in patients with.
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Cysticercotic encephalitis, angiitis, & arachnoiditis causing
progressive entrapment of cranial nerves.
Up to 32mg per day of dexamethasone.
May be used in association with mannitol at 2 mg/kg per day.
Followed by chronic oral therapy with prednisolone (50 mg/d).
Giant subarachnoid cysticerci(cerebral infarction),
Ventricular cysts (acute hydrocephalus),
Spinal cysts, (spinal cord swelling).
Multiple parenchymal brain cysts, (massive brain edema).
Simultaneous administration of corticosteroids and cysticidal
drugs ameliorate the secondary effects of headache and
vomiting that may occur during cysticidal drug therapy.
Treatment
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Surgical care:
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Hydrocephalus due to intraventricular cyst,
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Multiple cysts (the racemose) in subarachnoid space,
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Surgical extirpation, on an urgent basis, is recommended.
Obstruction is due to arachnoiditis,
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Ventricular shunt is recommended, followed by surgical
extirpation of the cyst and subsequent medical treatment.
Placement of a ventricular shunt should be followed by
administration of steroids and subsequent medical therapy.
Surgical treatment in the particular case of medically
refractory epilepsy due to a single lesion has been
reported.
Prevention
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Screen contacts
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Particularly relevant in nonendemic countries
Preventing human tapeworm infections
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Inspection of pork for cysticerci, which are visible in
raw meat ("measly meat")
Freezing or adequately cooking meat to destroy
cysticerci;

Pickling and salting are not adequate

Administering antiparasitic agents to pigs
Prevention

Preventing egg transmission to humans.




Education regarding routes of transmission.
Good personal hygiene and hand washing prior to
food preparation.
Identifying human carriers of tapeworms, possibly
through a history of proglottid passage, and
instituting targeted treatment.
Mass community anthelminthic programs to treat
tapeworm carriers.
Prevention

Preventing infections in pigs.



Confining the animals and not allowing them to roam freely to
avoid contact with infectious eggs excreted in human feces.
Improved sanitary conditions and proper disposal of human
stool.
Vaccine development.


There is no current human vaccine against T. solium.
Pigs actively infected or previously infected with the cyst stage
are immune to re-infection with oncospheres, suggesting that
vaccination should be feasible.
HIV and T.solium

Concurrent infection is expected to occur more frequently because of the
increasing frequency of HIV in endemic areas of cysticercosis.

However, little is known about the influence of HIV infection on the
frequency and the clinical course of cysticercosis.

Giant cysts & racemose neurocysticercosis seem to be more frequent in
HIV-infected patients

may be secondary to an uncontrolled parasitic growth because of an
impaired cell-mediated immune response.

In patients with advanced HIV disease and compromised cell-mediated
immunity, NCC may is exist without significant host response and is likely to
be asymptomatic. For this reason, in symptomatic patients with CD4 counts
under 200 cells/mm3 alternative diagnoses should be considered more
likely.