Neuroangiostrongyliasis (Rat Lungworm Disease)

Neuroangiostrongyliasis (NAS), or rat lungworm disease (RLWD), is an important emerging infection spreading around the world. It is caused by Angiostrongylus cantonensis, a nematode parasite, and is the commonest parasitic cause of eosinophilic meningitis. Infection can also cause cranial nerve (CN) palsies, encephalitis, and radiculomyelitis. Another form of the disease, ocular angiostrongyliasis, is very rare but occurs when a larval worm invades the eye.

Initial symptoms are nonspecific, and an early diagnosis requires a very high index of suspicion. Somewhat later in the course of the illness there may be more specific symptoms, but even then they can be very unusual and confusing, and the diagnosis still requires a high index of suspicion. Many infections result in a benign illness with recovery within a few weeks following symptomatic and supportive care. It has become increasingly recognized, however, that some infections, particularly in certain parts of the world, may result in more severe illness with long-term neurologic deficits, significant disability, and death.

A presumptive diagnosis is made by finding evidence of an eosinophilic meningitis in a patient with a history of suggestive symptoms who is living in or has traveled to an endemic region. The diagnosis can be confirmed by finding larvae in the cerebrospinal fluid (CSF) or the eye, but this is rare. It can also be confirmed by real-time polymerase chain reaction (RT-PCR) testing for A. cantonensis DNA in the CSF. This important test became available recently but is currently available only in the United States and a few other countries. If PCR testing is available, antibody testing is not usually recommended for diagnosis in an acute illness. Except in very mild cases, treatment with high-dose corticosteroids is recommended for almost all cases. Treatment with anthelminthics has been controversial for decades because of theoretical concerns that it could provoke a severe inflammatory reaction in the brain or spinal cord. Increasing experience, however, suggests that early treatment (ideally within 2–3 weeks of infection) with anthelminthics such as albendazole combined with high-dose corticosteroids is safe and effective. It remains to be seen, however, if this approach will reduce the incidence of chronic neurologic sequelae, long-term disability, and death in more severe cases.

Prevention involves adequately cooking intermediate hosts such as slugs and snails or transport hosts such as freshwater shrimps, freshwater crabs, frogs, and monitor lizards. Green leafy vegetables and fruits should be thoroughly washed to remove any contaminating slugs, snails, or mucus.

A 42-year-old organic farmer presented with a 2-day history of generalized headache. It was unusually severe, unlike any previous headaches he had had, and there was no associated fever. Past medical history was unremarkable. He lived on Hawaii Island in Hawaii and had no history of recent foreign travel. Physical examination by his primary care physician (PCP) was unremarkable, and he was diagnosed with tension-type headache. Ibuprofen and baclofen were prescribed.

Two days later he presented at a nearby urgent care clinic. His headache was worse, and he had developed shooting “electric shock” pains in his left arm and numbness in his right leg.

Physical examination was again unremarkable. His complete blood count (CBC) showed white blood cells (WBCs) 7800/mL, neutrophils 67%, lymphocytes 31%, and eosinophils 2%. A diagnosis of tension-type headache with anxiety was made and alprazolam was added to his drug regimen. Over the next 3 days his headache persisted, and the left arm pains became worse. In addition, he developed numbness in the left leg, and a sensation of “a thousand paper cuts” on the skin of his right leg.

Frustrated by worsening symptoms and lack of a specific diagnosis, he went to a nearby emergency room (ER). He was afebrile. Mild neck stiffness was noted but examination was otherwise unremarkable. His CBC showed WBCs 11,210/mL with 6% eosinophils. Computed tomography (CT) of the head was normal. He was told that he probably had stress headaches with anxiety, urged to follow up with his PCP, and referred to an outpatient neurologist.

By the following day the electric shock pains had become intolerable and were now described as like “ice picks.” In addition, he had developed nausea, night sweats, and insomnia. He sought care in another ER. A friend had told him about RLWD, and he refused to leave the ER until he had had a lumbar puncture (LP). This was done and showed slightly turbid CSF. The opening pressure was 240 mm H ₂ O (normal 60–200 mm H ₂ O). The CSF WBC count was 240/mL with 27% eosinophils. CSF protein was 49 mg/dL (normal 28–38 mg/dL).

Further history revealed that the patient often ate food directly from his farm and did not routinely examine or wash green leafy vegetables before consuming them. There was no history of intentionally eating raw slugs, snails, shrimp, or other unusual uncooked foods. He recollected that about 7 days prior to the onset of his headache he had experienced a few days of malaise with transient upper abdominal pain, nausea, and diarrhea associated with a cough and sore throat. Following his LP, a diagnosis of eosinophilic meningitis was made, with a presumptive diagnosis of NAS. CSF was sent for RT-PCR testing for A. cantonensis DNA. He was admitted to hospital and promptly started on treatment with high-dose corticosteroids and albendazole. The diagnosis of NAS was confirmed 3 days later with a positive PCR result.

COMMENT: There was no clear exposure history, but this patient may have been infected after unintentionally swallowing a slug hidden in unwashed salad vegetables from his farm. Symptoms prior to the onset of his headache may have been caused by migrating parasites on their way to the brain and spinal cord. He had a confusing array of very unusual migratory symptoms that led to a delay in diagnosis, fragmented care, and his resulting frustration. There were certain “red flags” that were not immediately recognized. These included an unprecedented severe headache and significant eosinophilia on his first ER visit; these could have prompted a more focused workup at an earlier stage of his illness. A detailed food history would have revealed that he had eaten unwashed salad vegetables directly from his farm, a significant risk factor for NAS. In addition, questioning regarding a prodromal illness might have prompted a more focused workup and resulted in an earlier diagnosis.