Stephen B. Tatter, MD, PhD * and Jonathan W. Hopkins, MD**
* From the Department of Neurosurgery,
Bowman Gray School of Medicine,
Wake Forest University, Winston-Salem, North Carolina, USA,
and
** Neurosurgery of Kalamazoo,
Bronson Medical Center, Kalamazoo, Michigan, USA
Humans are the definitive host for the nematode, round-worm Ascaris lumbricoides, which generally produces only mild systemic symptoms. The authors report two cases of intestinal A. lumbricoides with concurrent cerebral manifestations. A 53-year-old Syrian woman with intestinal A. lumbricoides presented with a generalized seizure and a cerebral lesion that worsened for several days and then resolved after treatment with mebendazole. Magnetic resonance imaging revealed a 2-cm lesion in the right mesial temporal lobe. The lesion was hypointense to brain on T1-weighted images and hyperintense on T2-weighted images. There was a small focus of central enhancement. The second patient, a 2-year-old girl, died of a brain abscess with six organisms, including Neisseria mucosa, Eikenella corrodens, and microaerophillic streptococcus. The hypothesis that A. Lumbricoides served as a vector for these bacterial pathogens, as well as potential alternative roles of A. lumbricoides in causing a polymicrobial bacterial abscess, are discussed. These cases suggest that specific treatment strategies including antihelminthic therapy or abscess resection may be successful in patients with cerebral lesions and concomitant intestinal A. lumbricoides.
Key Words: helminthiasis, larva migrans, brain abscess, temporal lobe epilepsy, nematode infection
Ascaris lumbricoides is the member of the nematode superfamily Ascaridoidea for which humans are the definitive host. Ascaridoidea generally cause only mild systemic symptoms in their definitive hosts, while infection of aberrant hosts is often widespread and is characterized by fatal eosinophilic meningoencephalitis. Human examples of central nervous system manifestations of Ascaridoidea other than A. lumbricoides are well known. They include ocular larva migrans (Raymond et al., 1978) and death due to eosinophilic meningoencephalitis (Huff et al., 1984). Cerebral lesions consistent with cerebral A. lumbricoides larva migrans have not been previously reported. Seizures and meningitis have been observed in patients with intestinal ascariasis, but in these instances, evidence of cerebral infection by larvae is lacking (Duprey, 1903; Fernando and Balasingham, 1943). Conversely, an Ascaris larva was detected incidentally in the thalamus of a patient who died of acute poliomyelitis (Beautyman and Woolf, 1951). We present two cases in which concurrent intestinal A. lumbricoides and symptomatic cerebral lesions occurred. The nature of these lesions and their response to therapy suggest that cerebral A. lumbricoides larva migrans accounts for the findings in each case. They also demonstrate that an awareness of possible cerebral manifestations of intestinal ascariasis may lead to therapies that minimize risks and improve outcomes in affected patients.
This 53-year-old Syrian woman developed neurologic symptoms two months after traveling to the USA. Two weeks before admission to the hospital, the patient began to experience vivid nightmares. Several days later she became anorectic and mildly lethargic. On the day of her admission to the hospital she experienced a generalized seizure. A lumbar puncture was normal except for the presence of 1 white blood cell and 4 red blood cells per ml. 86% of the cerebrospinal fluid white cells were lymphocytes and 14% were monocytes. Serum was negative for antibodies to Echinococcus granulosa or cysticercosis (Force et al., 1992; Tsang et al., 1989). The antitoxoplasma immunoglobulin (Ig)-G titer was 113 IU/ml, and there was no antitoxoplasma IgM detected. A stool examination revealed fertile eggs of A. lumbricoides. Magnetic resonance imaging (MRI) demonstrated a 2-cm right mesial temporal lesion at the gray-white junction. The lesion was hypointense to brain on T1-weighted images, and hyperintense on T2-weighted images (Figs. 1, 2). There was a small focus of central enhancement after intravenous gadolinium-diethylenetriamine pentaacetic acid (DTPA, Fig. 1).
Six weeks after this admission, she was referred to one of the authors (SBT) for possible brain biopsy. Her nightmares, anorexia, and lethargy persisted. In addition, she had developed mild headaches that responded poorly to acetaminophen or ibuprofen. Because of her untreated A. lumbricoides infection, oral mebendazole, 100 mg twice a day for three days, was prescribed. Her headaches, nightmares, anorexia, and lethargy worsened for four days after the first dose of mebendazole. Her symptoms resolved completely over the next three days. An MRI with and without gadolinium four weeks after her mebendazole therapy showed no mesial temporal lesion (Fig. 2, bottom). She remains well with no evidence of cerebral pathology on repeat MRI five years later.
This 2-year-old girl experienced 1 week of episodic fever accompanied by nausea, emesis, and progressive irritability. Examination at a hospital near her home revealed mild lethargy. A lumbar puncture was normal except for an elevated protein of 120 mg/dl. The patient passed an A. lumbricoides adult in her stool and was treated with oral piperazine citrate. She presented to our (JWH) emergency department 5 days later. Neurologic examination found coma with a dilated left pupil that was unresponsive to light, while CT scan demonstrated a 5-cm diameter, multiloculated, low-density mass in the right parietal and occipital lobes. There was a rim of enhancement after intravenous contrast.
Bur hole drainage of the abscess revealed purulent material under pressure. Cultures grew Neisseria mucosa, Eikenella corrodens, microaerophillic streptococcus, non-group-D alpha-hemolytic streptococcus, proprionobacterium, and a sixth organism that was not identified. She was treated with phenytoin and appropriate antibiotics. Reexploration revealed accumulation of purulent material that was again drained and irrigated. She responded well to both operations, gradually becoming alert and conversant with a residual right hemianopsia and a mild right hemiparesis. Approximately 1 week after each operation, she again became unresponsive and developed an acute third nerve palsy on the left side. Therefore, a third, more extensive exploration was undertaken. The patient remained unresponsive and ventilator-dependent postoperatively. She could not be resuscitated after cardiac arrest 10 months later. An autopsy performed 1 year after the onset of her symptoms revealed only extensive cerebral necrosis. Medico-legal aspects of this case have been described (Kean, 1990).
A. lumbricoides is among the most common human helminthic infections. Fertilized eggs develop in warm, moist soil into infective eggs containing larvae. When these eggs are ingested, the emerging larvae penetrate the intestinal wall and migrate to the lungs through the portal vein, liver, and heart. The larvae then migrate from capillaries to air spaces, and then to the gastrointestinal tract-a route that may be assisted by coughing. The larvae attach in the jejunum or ileum, where they mature into adults. Male and females then copulate, after which approximately 200,000 eggs a day are produced. The eggs remain viable in soil for years despite freezing and drying (Piggott et al., 1970). Systemic larva migrans can occur when there is a right-to-left shunt in the heart or if the larvae bypass the lungs, presumably using mechanisms similar to those used to circumvent the liver.
In the present cases, no tissue was obtained to confirm an A. lumbricoides larva as the cause of the cerebral lesions apparent on MRI and CT scan. In Case 1, the acute deterioration followed by a rapid recovery after a therapeutic trial of mebendazole--which is active against susceptible cerebral parasites--strongly suggests that a helminth was the cause of this patient's symptoms. The absence of antibody to Echinococcus granulosa and cysticercosis makes these parasites unlikely (Force et al., 1992; Tsang et al., 1989). Similarly, the absence of IgM to toxoplasma makes acute infection with this organism unlikely. In addition, toxoplasmosis is entirely resistant to mebendazole therapy. This, plus the presence of fertile eggs in the patient's stool, implicates a cerebral A. lumbricoides larva as the probable causative organism.
In Case 2, A. lumbricoides might have played a role in the pathogenesis of the abscess by one or more assorted routes. Several of the organisms cultured are common in the oral pharynx, and are found throughout the gastrointestinal and respiratory tracts, and are rare causes of central nervous system pathology (Cheng et al., 1988; Pit et al., 1993; Porphyris, 1983; Stotka et al., 1991; Swanston et al., 1988). A. lumbricoides is suggested as a possible source of these organisms by the presence of adult worms in the patient's stool several weeks after the onset of her symptoms. The presence of multiple organisms characteristic of the respiratory tract in the abscess most likely resulted from an A. lumbricoides larva serving as a vector, carrying bacteria acquired during aberrant migration from the pulmonary to the systemic circulation. Support for this hypothesis is found in the failure of this abscess to respond to appropriate antibiotics and two attempts at surgical drainage, which clinically suggested the presence of a foreign body.
A. lumbricoides infection might alternatively have contributed to the formation of a bacterial brain abscess with multiple respiratory flora, by one of several other mechanisms. For example, the parasites may allow systemic entry of the bacteria by breaking a mucosal barrier in the gastrointestinal or respiratory tract. A. lumbricoides is also known to induce an eosinophilic pneumonitis during its pulmonary migration; this is predicted to cause a right-to-left shunting of blood if a patent foramen ovale exists in the heart. Such a shunt predisposes to the formation of cerebral abscesses. Another mechanism by which A. lumbricoides could elicit such an unusual brain abscess is by causing a subclinical aspiration pneumonia during its migration up the respiratory tract. The patient's lack of respiratory symptoms and findings clinically suggests that neither of the alternatives involving pneumonia or pneumonitis played a prominent role in the pathogenesis of her cerebral abscess.
Because the host response to A. lumbricoides in humans is mild, neuroimaging might be expected to provide a number of clues to suggest this organism as the cause of an intracranial lesion. In Case 1, the lesion was not visible in a high-quality noncontrast CT scan, even in retrospect. The amount of tissue reaction was small, as was the region of central enhancement. In addition, cerebral ascariasis may deliver enteric bacteria to the central nervous system, causing the more extensive findings typical of an abscess, as demonstrated in Case 2.
No specific serologic or other tests are available to diagnose ascaris larva migrans. Histologic diagnosis is the only definitive test. In mild cases of cerebral larva migrans (similar to the proposed pathophysiology in our Case 1), a brain biopsy would be contraindicated because of the rapid response expected to systemic antihelminthics such as albendazole. In such instances, presumptive therapy would need to be instituted based on the finding of fertile Ascaris eggs or of adult worms in the patient's stool. Alternatively, a therapeutic trial of an antihelminthic drug might be appropriate in a patient with a history of environmental exposure to A. lumbricoides and neuroimaging suggestive of possible cerebral ascariasis.
In cases complicated by brain abscess (similar to our Case 2), early craniotomy would be the procedure of choice. Early surgery in such a case would offer the opportunity of obtaining a definitive diagnosis and of curing this potentially lethal infection.
Cerebral abscesses with multiple non-otogenic respiratory bacteria are extremely rare (Brook, 1981 and 1992; Domingo and Peter, 1994; Garvey, 1983; Gower et al., 1990; Pit et al., 1993; Renier et al., 1988; Yang, 1981). Although such abscesses have not been commonly observed as cerebral manifestations of parasite infection (Bia and Barry, 1986), discovery of such an abscess suggests the possibility of parasitic migration from the respiratory or gastrointestinal tract to the brain. Case 2 illustrates the difficulty of treating an abscess associated with a foreign body by aspiration. We, therefore, recommend that excision of the abscess be considered when possible, to ensure removal of a potentially causative larva in cases of a cerebral abscess with multiple respiratory or enteric bacteria and concomitant A. lumbricoides infection.
A. lumbricoides should be suspected in any patient from an endemic area or exposed to an infected individual. Neuroimaging may suggest the diagnosis, as should an abscess with multiple bacterial species. The finding of fertile eggs or adults in the stool further supports the hypothesis. In the absence of a bacterial abscess, it is likely that cerebral A. lumbricoides is usually self-limiting, given that no other symptomatic cases have been previously reported. Treatment with a systemically active anti-helminthic, such as mebendazole or the better absorbed albendazole, would be expected to speed the removal of the offending larva (Del Brutto et al., 1993; Todorov et al., 1992). As in Case 1, a transient worsening of symptoms may occur as the larva dies, and may necessitate steroid therapy, shunting, or craniotomy.
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Address reprint requests and correspondence to Stephen B. Tatter, MD, PhD, Department of Neurosurgery, Bowman Gray School of Medicine, Winston-Salem, NC 27157-1029, USA; E-mail statter@bgsm.edu; Phone (910) 716-4047; Fax: (910) 716-3065.