Tropical Medicine 7: Neurological Manifestations
Central Nervous System Infections
Acute Encephalitis
Acute encephalitis, resulting in altered cognition, seizure, focal neurological
(motor and sensory) deficits, decreased consciousness, and neuropsychiatric
symptoms may result from a variety of etiologies common in the tropics, in
addition to the strokes, trauma, and dementia encountered worldwide. These are
discussed in this portal.
Arbovirus Infection
Arthropod-borne
viruses are responsible for CNS infections. These include
Venezuelan Equine (VEE), Japanese
(JE), Eastern Equine (EEE), Western Equine
(WEE) Encephalitis viruses, West Nile virus, St. Louis virus, and others.
Clinical presentations are similar, and variable in their severity. Nonspecific symptoms of fever, malaise, cephalgia, myalgia, and GI upset may be followed by more serious CNS symptoms such as ataxia, aphasia, seizure, paralysis, or coma. Death due to respiratory arrest may occur.
Diagnosis is clinical supplemented by serology. Treatment is supportive; antivirals do not appear to be beneficial.
Polio
Transmitted via the fecal-oral or
oral-oral route, polio is asymptomatic in over
90% of patients.1
For those who do develop symptoms, nonspecific
viral illness
symptoms arise within a week of infection. Over the next 2 to 3 weeks,
neurological symptoms develop, ranging from aseptic meningitis to
flaccid
paralysis and fever. The paralysis is asymmetrical, and the sensory
system is not
affected. Once the fever abates, no further progression of the
paralysis generally
occurs. Fatality is due to respiratory paralysis, with a 5% to 10% rate1 (variable
between age groups). A postpolio syndrome of myalgia or worsening of existing
weakness may occur up to 40 years after paralytic poliomyelitis in 25% to 40% of
patents.1
Diagnosis is clinical; culture is helpful, and serology may not be. Treatment is supportive, including mechanical ventilation if necessary.
Rabies
A viral zoonosis,
humans may become infected through exposure to body fluids
of infected animals (typically a bite or scratch). Following the
infection, there is
an incubation period from 4 days to >19 years, though typically 30
to 90 days. A
prodromal phase follows, with parasthesias (pruritis), fever,
moodiness, and
upper respiratory
tract infection (URI) or acute gastroenteritis (AGE) symptoms. After a
few days, the disease becomes apparent. The two clinical presentations
in
humans are furious and
paralytic rabies.
Furious rabies exhibits the pathognomonic hydrophobia. Respiratory spasms (occasionally accompanied by generalized seizures and even cardiac or respiratory arrest) follow exposure to water or a gust of air on the face. Abject, unexplainable terror is prominent along with the spasm. Asymptomatic periods are interspersed with times of hallucination and aggression. Meningeal signs, such as cranial nerve lesions and upper motor lesions, may be seen along with involuntary movements, lacrimation, sweating, salivation, and SIADH (Syndrome of Inappropriate Antidiuretic Hormone). Patients die either in the midst of the spasm, or slip into a coma and eventually die of respiratory failure.
Paralytic rabies develops flaccid paralysis ascending from the site of inoculation after the typical prodrome. There may be pain and mild sensory disturbances. Patients die of paralysis of the respiratory muscles after a prolonged course.
Diagnosis is clinical, supplemented with immunostained histology and viral isolation from body fluids. Until recently, the condition was universally fatal. At the time of this writing, there has been one survivor who was pharmacologically paralyzed and mechanically ventilated for an extended time, received high dose antivirals, and survived relatively intact.2,3 Prompt transfer to an aggressive tertiary care center is the only hope for patients with rabies.
Measles
This formerly common childhood viral infection may result in three
forms of
encephalitis. Acute postinfectious measles
encephalitis
occurs just under a week after appearance
of the rash in older children and has up to 20% fatality
rate.1,4 Many who survive do so with varying
degrees of impairment. Acute progressive encephalitis occurs in immunosuppressed individuals.
Subacute sclerosing panencephalitis (SSPE) is a late complication of slowly progressing
personality and intellectual changes, developing to myoclonus, ataxia, blindness
or coma. Diagnosis is clinical, based on history of the disease, and treatment is
supportive.
Cerebral Malaria
Falciparum malaria may cause a variety
of neurological manifestations, due to
the sequestering of parasitized erythrocytes in the intracranial capillaries. Accompanied by high
fever, diagnosis is through demonstration of the parasite
on blood smears. Prompt diagnosis and parenteral antimalarial treatment is
essential to survival with minimal residual deficits. (Vol III—TM3 Fever and Systemic Manifestations)
Trypanosomiasis
African
trypanosomes are transmitted by
the
bite of the tsetse fly. The organisms
multiply in the lymphatics, and are released into circulation in waves.
Acutely, fever, arthralgia, and cephalgia are accompanied by
lymphadenopathy
(Winterbottom’s sign). This may last months, until CNS invasion
symptoms
become apparent. Behavioral changes, psychiatric symptoms, and
disordered
sleep (hence, sleeping
sickness) are common. Focal deficits are uncommon, but
cerebellar dysfunction becomes apparent near the end. Death occurs
within a few
months of the appearance of CNS symptoms.
Diagnosis is made by identification of the organism on blood smear (challenging, as parasitemia levels are very low) or lymph node or marrow aspiration. Serology is also available.
Treatment is fairly toxic, and presented in Vol III—TM13 Antiparasitic Primer.
Toxoplasmosis
Toxoplasma (T gondii) is an obligate intracellular parasite acquired via ingestion of
cysts in undercooked meat or in food contaminated by cat feces (due to lack of
hand-washing). Usually asymptomatic, T gondii may cause an acute
mononucleosis. Its greatest significance is in
perinatal transmission (not covered
here) and in the immunocompromised, where the long-latent tissue cysts
reactivate. In the latter
case, focal neurological symptoms, or diffuse
involvement
of the CNS may develop. Rarely, pulmonary symptoms may be present, based
on the presence of the latent cysts.
Diagnosis is identification of the organisms in tissue or centrifuged body fluids in reactivated cases. Serology may help. Treatment is pyrimethamine 50 mg PO 4 times daily (75 mg the first day) plus sulfadiazine 5 g PO weekly plus calcium folinate 15 mg PO 3 times weekly, all for a minimum of 4 weeks. This is followed by pyrimethamine 25 mg PO plus sulfadiazine 2 g PO, 3 times weekly for life.
Naegleria
A free-living
amoeba, this organism penetrates the nasal mucosa when the fresh
water in which it lives
is inadvertently snorted. It migrates to the CNS and may cause acute
encephalitis. Diagnosis is identification of the organism in the CSF.
Metronidazole is the treatment of choice (Vol III—TM13 Antiparasitic Primer). This is rare, fortunately.
Neurocysticercosis
Tapeworm cysts, discussed in TM4 (Vol III—TM13 Antiparasitic Primer) and TM6 (Vol III—TM6 Muscular Manifestations), may also occur in the CNS. This
condition is
a leading cause of adult-onset
seizure disorder in endemic regions. Seizures are a common presenting
complaint, as are chronic headaches. Focal neurological signs may be present, as
may psychiatric symptoms and dementia. Hydrocephalus, encephalitis, cerebral
edema, and infarcts may develop. Occular or spinal cord involvement is less
common. Imaging aids in diagnosis, though it is often not available in endemic
regions.
Diagnostic criteria are shown in the table below.
Definitive diagnosis requires 1 absolute plus
2 major criteria OR
1 major plus 2 minor plus 1 epidemiological criteria.
Probable diagnosis requires 1 major plus 2 minor criteria OR
1 major plus 1 minor plus 1 epidemiological criteria OR
3 minor plus 1 epidemiological criteria.
Possible diagnosis requires 1 major plus 2 minor
OR
1 minor plus 1 epidemiological criteria.
Diagnostic Criteria for Neurocysticercosis
| Absolute | Major | Minor | Epidemiologic |
|
|
|
|
The efficacy of medical treatment is subject to debate, but both albendazole (eg, 15 mg/kg/day, twice daily, for 28 days) and praziquantel (eg, 50 mg/kg/day, three times daily, for 15 days) have been used with some degree of success. Some experts recommend pretreatment with steroids, and most recommend anticonvulsants.
Similarly, hydatid cysts (Vol III—TM4 Gastrointestinal and Abdominal Manifestations) may also form space-occupying lesions intracranially.
Aberrant Helminth Migration
As
noted in other chapters, many helminthic
parasites migrate to their final
location in their human host in the course of their maturation to adult
worms. Occasionally, they may get lost and end up in ectopic sites
where their presence
causes inflammation and other pathology. Antiparasitic treatment (based
on
diagnosis of the infection in its proper site) may benefit individuals
also suffering
from these aberrant migrations.
Spinal Cord and Peripheral Nerve Disease
Tuberculosis
Extrapulmonary tuberculosis is often misdiagnosed because its
symptoms mimic those of many other, more common conditions. It may present as a spinal cord
lesion (due to granuloma formation) or chronic meningitis. Antitubercular therapy
(Vol III—TM9 Pulmonary Manifestations) is beneficial, though residual deficits may persist.
Meningococcus
Neisseria meningitides (N meningitides),
a highly contagious organism responsible
for epidemic outbreaks, is a significant cause
of morbidity and mortality. Symptoms include cephalgia with
photophobia, fever, altered consciousness, meningeal signs, and a
slightly raised (thus palpable) rash. Mortality may be as
high as 50%,5 and successfully treated patients may have persistent disabilities.
Diagnosis is by lumbar puncture, in which the CSF will demonstrate high opening pressure, turbidity, neutrophils, low glucose, high protein, and gram-negative diplococci.
Treatment consists of ampicillin 2 g IV every 6 hours for 10 days, along with aggressive supportive care. Household contacts should receive prophylaxis of rifampin 600 mg PO twice daily for 2 days (PEDS: 10 mg/kg for children; 5 mg/kg for infants under 1 year of age). Fortunately, significant antibiotic resistance has not emerged in meningococcus. This highly contagious organism could cause great devastation without effective treatment.
Cryptococcus
Cryptococcus is a fungal organism that may
present as pneumonia, disseminated
disease, or as subacute meningitis. Since pneumonia is uncommon
and generally mild, disseminated disease is significant
only to the immunocompromised.
Clinically, it mimics tuberculous meningitis with fever, cranial nerve palsies, and
visual disturbances. Meningeal signs are less
common, and a rash (containing the
organism) is often present. Fatality rate may as high as 70%.5 Cryptococcus
is universally fatal without treatment.
Diagnosis is by lumbar puncture with lymphocytes, elevated protein, and organisms noted on stain or culture. Serology is of value. Treatment is traditionally amphotericin B 0.5 mg/kg/day plus flucytosine 100 mg/kg/day for several weeks. Fluconazole 400 mg 4 times daily is also effective with fewer side effects. Recurrence is common in the immunosuppressed for whom fluconazole 200 mg 4 times daily is good secondary prophylaxis.
Tropical Ataxic Myelopathy
Occasionally seen in immigrants, this condition is unlikely in expatriates. The
ataxia, hearing/vision
loss, and polyneuropathy is related to chronic cyanide
intoxication (dietary), riboflavin deficiency, and low ceruloplasmin
levels. Another condition, tropical spastic paraparesis, is related to cyanide poisoning
from dietary cassava intake.
Leprosy
As noted in TM5 (Vol III—TM5 Dermatological Manifestations), tuberculoid leprosy is associated with
peripheral neuropathy.
Botulism
Most commonly the result of ingestion of Clostridium neurotoxins in improperly
canned foods, this paralytic disease may be life--threatening. It may
rarely be acquired by contamination of wounds with the spores of the organism.
Symptoms begin 12 to 48 hours post ingestion and are initially vague
complaints of weakness, fatigue, and dizziness. GI symptoms may be present as
well. Symptoms progress to
cranial nerve palsies, diplopia, dysphagia, dysphonia, dysarthria,
descending flaccid paralysis of the extremities, and even
respiratory paralysis.
Diagnosis is generally clinical, with bioassay and ELISA for the toxin supplementing it. Stool culture may be positive. Treatment is primarily supportive. Antitoxin is beneficial; antibiotics generally are not.
Miscellaneous
Metabolic and toxic conditions (diabetes, alcohol) may also cause neurological
symptoms, as can trauma and other infectious diseases (such as
diphtheria, leprosy, trichinosis, cysticercosis, leptospirosis,
relapsing fevers, typhus, rabies, etc). These are discussed elsewhere
in this portal and the CALS course.
References
- Strickland GT, editor. Hunter’s tropical medicine and emerging infectious diseases, 8th ed. Philadelphia, PA: WB Saunders, 2000.
- Recovery of a patient from clinical rabies—Wisconsin, 2004. MMWR. 2004 Dec 24;53(50):1171-1173. Available at http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5350a1.htm. Accessed March 18, 2008.
- Jackson AC, Warrell MJ, Rupprecht CE, et al. Management of rabies in humans. Clin Infect Dis. 2003;36:60-63.
- Guerrant RL, Walker DH, and Weller PF, eds. Tropical infectious diseases: principles, pathogens, and practice. Philadelphia: Churchill-Livingstone, 1999.
- Gill GV, Beeching NJ. Lecture notes in tropical medicine, 5th ed. Malden, MA: Blackwell Science, 2004.