MATTHEW TEST
SAMIR S. SHAH
HISTORY OF PRESENT ILLNESS
A 12-year-old boy had difficulty rising from a sitting position when asked to do so at a basketball game 2 days before admission. He was able to stand only after several minutes, and he attributed this episode to fatigue. Later that evening, while lying on the couch at home, he again had difficulty standing and required assistance from his mother. He was eventually able to walk upstairs unassisted. His mother found him several minutes later, lying on the floor, staring, open-mouthed, and drooling. He had spontaneous respirations but was unresponsive to verbal stimuli. He was taken to a nearby hospital by ambulance.
On arrival, the patient was somnolent but arousable, with a Glasgow coma score of 10. He then experienced an episode of staring, unresponsiveness to verbal stimuli, and right hand shaking that lasted 10 minutes, stopping only after administration of rectal diazepam followed by intravenous lorazepam (0.05 mg/kg) and phenytoin. Unenhanced CT imaging of the head revealed normalsized ventricles without evidence of midline shift. Opening pressure on the lumbar puncture was 18 mmH2O. After a CSF sample was sent for laboratory analysis, the patient received ceftriaxone intravenously.
He was transferred to another institution for additional management. Discussion with family members did not reveal a history of fevers, night sweats, vomiting, behavior or personality changes, or ataxia. There was no history of witnessed ingestion or trauma.
MEDICAL HISTORY
The patient was born in Mexico and emigrated to the United States when he was 9 years old. His perinatal history was unremarkable. Specifically, there were no maternal infections during pregnancy. The patient was born at term gestation after an uncomplicated delivery. He had never been hospitalized and did not take any prescription medications. There was no family history of seizures.
PHYSICAL EXAMINATION
T 36.7°C; RR 18/min; HR 60 bpm; BP 111/67 mmHg
Height 50th percentile; Weight 5th percentile
On examination, the patient was somnolent but easily arousable and was able to answer questions appropriately. His appearance was thin but not cachectic. There was no papilledema or scleral icterus. His pupils were symmetrically reactive to light. His neck was supple. There was no hepatomegaly, splenomegaly, or lymphadenopathy. There were no hypopigmented or hyperpigmented skin lesions. The remainder of the physical examination, including the neurologic examination, was normal.
DIAGNOSTIC STUDIES
The complete blood count revealed 11 400 WBCs/mm3 (86% segmented neutrophils, 9% lymphocytes, and 5% monocytes); hemoglobin, 12.2 g/dL; and platelets, 257 000/mm3. Serum electrolytes, calcium, blood urea nitrogen, and creatinine were normal. The serum glucose was 166 mg/dL, and the phenytoin level was 18.1 mg/L (normal therapeutic range, 10-20 mg/L).
Examination of the CSF revealed no WBCs and only 1 RBC/mm3. The protein concentration was 11 mg/dL, and glucose was 93 mg/dL. There were no organisms on Gram stain of the CSF. An acid-fast stained smear of CSF was negative. An ECG demonstrated sinus bradycardia but was otherwise normal. Echocardiogram and EEG were also normal.
COURSE OF ILLNESS
The patient continued taking phenytoin and did not have any further complex partial seizures. MRI of the head performed, with intravenous gadolinium (Figure 19-8), was considered diagnostic.
FIGURE 19-8. Intravenous gadolinium-enhanced magnetic resonance image of the head.
DISCUSSION CASE 19-6
DIFFERENTIAL DIAGNOSIS
Partial seizures are less common in children than in adults, accounting for about 45% of all childhood seizure disorders. In contrast to adults, most complex partial seizures in children are idiopathic. These typically occur as manifestations of one of the so-called benign focal epilepsy syndromes of childhood. The differential diagnosis in this patient also includes early-onset posttraumatic epilepsy, which is associated with partial seizures in the older child. Onset is within 24 hours of the injury in 50% of cases. The incidence of traumatic epilepsy is relatively small in closed-head injuries. Infectious causes of partial seizures should always be considered in this age group. Viral encephalitis due to HSV or Epstein-Barr virus is possible. Subacute sclerosing panencephalitis, associated with measles infection, is less likely, but knowledge of the patient’s immunization history is important. Parasitic infection of the CNS may result in partial seizures. Neurocysticercosis has a high prevalence in developing areas of Central and South America, and echinococcosis is hyperendemic in areas of South America, central Asia, and the western United States. Tuberculosis with tuberculoma formation in the brain continues to be a problem in some parts of the world. Less common causes of partial seizures in this age group include brain tumors, which are present in fewer than 10% of children with partial seizures. Nevertheless, focal seizures accompanied by a history of headaches may be caused by a CNS tumor. Cerebrovascular disease causing a partial seizure is unlikely unless predisposing factors such as sickle cell disease or an inherited thrombotic disorder (e.g., factor V Leiden mutation, protein C or S deficiency) are present. Bacterial endocarditis with cerebral emboli can cause partial seizures but is usually associated with persistent fever and an abnormal echocardiogram. An important clue to the diagnosis in this case was the patient’s history of emigration from Mexico, an area of high prevalence for certain parasitic diseases.
DIAGNOSIS
Intravenous gadolinium-enhanced head MRI revealed a 10-mm ring-enhancing lesion in the left parietal white matter with surrounding vasogenic edema and localized mass effect (Figure 19-8). There was no evidence of elevated intracranial pressure. These findings were consistent with the diagnosis of neurocysticercosis. Intravenous dexamethasone, which was started before his arrival at the current institution, was discontinued. Cultures of blood and CSF were negative, and antimicrobial therapy was discontinued. Cysticidal therapy was not recommended. The patient was discharged on phenytoin after a period of observation. On follow-up 1-year later, he had remained seizure free.
INCIDENCE AND EPIDEMIOLOGY OF NEUROCYSTICERCOSIS
Neurocysticercosis is the most common parasitic infection of the CNS. It is caused by the pork tapeworm Taenia solium. The disease is highly endemicin Latin America, Mexico, Eastern Europe, Asia, Africa, and Spain. In the United States, the infection is most common among immigrants from endemic areas and children in contact with these immigrants, and it is estimated that there are more than 1000 new cases of neurocysticercosis in the United States each year. Cysticercosis can affect humans at any age including infection by the transplacental route. It is most common during the third and fourth decades of life; only 10% of individuals with neurocysticercosis are children. The estimated serologic prevalence of cysticercosis in Mexican adults is 3.6%, with positive confirmation at autopsy in 1.9%.
Taenia solium is a gastrointestinal tapeworm (cestode) that causes two types of disease syndromes. Intestinal infection with the adult tapeworm occurs when infective larvae are ingested in undercooked pork. Cysticercosis occurs when humans ingest food contaminated with feces containing T. solium eggs. The eggs hatch in the intestine, liberating embryos. The embryos penetrate through the intestinal mucosa and are disseminated by the blood to brain (neurocysticercosis), subcutaneous tissues, muscle, and eye, where they develop into cysticerci. Cysterci are often 5 mm in diameter, but may enlarge to 50 mm. Within the brain, cysts are most commonly located in the parietal lobes.
CLINICAL PRESENTATION OF NEUROCYSTICERCOSIS
The clinical manifestations in children are different from those in adults. The initial sign of neurocysticercosis in children is usually (>80% of cases) the new onset of focal or generalized seizures. Rare presentations in children include hemiparesis, increased intracranial pressure with headache and vomiting, encephalitis, meningitis, and simulation of a psychotic illness with delirium or hallucinations. Although some children have several parenchymal cysts, most children (75%) have a solitary lesion.
Adolescents and young adults who develop seizures due to neurocysticercosis often have a calcified brain granuloma. The cysticerci remain clinically silent during the natural course of infection, immune reaction, parasite destruction, and granuloma formation. After several years, as evidenced by calcification of the granuloma, the patient develops epilepsy. Adult disease with acute presentation is characterized by multiple brain cysts and an intense immune response. Approximately 30% of adults present with signs of increased intracranial pressure.
DIAGNOSTIC APPROACH
Head CT or MRI. Contrast-enhanced CT and MRI of the head are diagnostic. CT most commonly reveals single, small cysticerci (ring-enhancing) with surrounding edema, granuloma, or calcification. Disseminated infection with multiple parenchymal cysts is identified by a “starry sky” appearance. MRI is the best imaging test overall for the diagnosis and should be performed on all patients for whom the clinical history and CT scan suggest the diagnosis of neurocysticercosis. The cysticerci may not be clearly visible on noncontrast CT of the head.
Enzyme-linked immunotransfer blot (EITB). EITB of serum or CSF can assist in confirming a presumptive clinical and radiographic diagnosis. The specificity is approximately 100%. In patients with more than two lesions, the sensitivity is greater than 90%. However, the test is often negative in patients with solitary or calcified lesions (75% of children). Excretory secretory (ES) antigens are a mixture of protein products of live tapeworm larvae, and an immune response to these antigens is thought to indicate the presence of live parasite. Recent use of ES antigen in EITB showed a sensitivity of 85.6% in the identification of solitary lesions (n = 111) and 100% in the identification of calcified lesions (n = 5). However, the specificity was 64%.
Stool testing for ova and parasites. All children with neurocysticercosis and their contacts should have their stool examined for T. solium ova on three consecutive daily specimens. The source of infection in children is frequently infected stools of family members or other close contacts. Such testing may prevent further exposure and transmission of the disease.
EEG. An EEG should be performed to assist in localizing seizures in all children with partial seizures.
Lumbar puncture. Examination of the CSF often reveals elevated protein and a mild lymphocytic pleocytosis (mean, 59 WBCs/mm3).
TREATMENT
In children, an isolated cystic lesion in the brain parenchyma usually does not require treatment. In these patients, ring enhancement demonstrated on contrast-enhanced CT is associated with inflammation around a dead or dying parasite. Because a solitary lesion usually disappears spontaneously within 2-3 months, the use of antihelminthic therapy in this setting is controversial (Table 19-4). A 2010 Cochrane Review identified studies comparing albendazole therapy to no treatment. The authors found that, in children with nonviable (enhancing on neuroimaging) lesions, administration of albendazole was associated with significant reduction in seizure recurrence but no change in cyst persistence. In those adults with viable (non-enhancing on neuroimaging) lesions, there was no change in seizure recurrence, but albendazole administration was associated with decreased cyst persistence. There were no trials involving viable lesions in children. A recent study demonstrated no benefit of albendazole and praziquantel combination therapy over albendazole monotherapy in lesion eradication or seizure prevention. Children with the highest risk of chronic seizures are those with a calcified granuloma (indicating a dead parasite) that remains as a permanent sequelae of the cysticercus.
TABLE 19-4. Randomized controlled trials in children with neurocysticercosis presenting with nonviable lesions.
Those with multiple lesions or viable cysticerci without radiographic evidence of inflammation need therapy. Albendazole for 28 days is the recommended cysticidal therapy and in most cases results in complete disappearance or significant regression in cyst volume. If albendazole results in only a partial response, praziquantel may be given for 14 days. Individuals whose stool examination reveals adult T. solium should be treated with a single dose of praziquantel to prevent transmission.
Initiation of cysticidal therapy may result in cerebral edema. Therefore, dexamethasone should be given 2 days before cysticidal therapy and continued during therapy and shortly after its completion. Dexamethasone therapy should not be given in the absence of antihelminthic drugs, as dexamethasone alone has been associated with increased seizure recurrence. Of note, dexamethasone lowers plasma levels of praziquantel by as much as 50% but raises the level of albendazole by 50%. Anticonvulsant therapy is also often required. In children with degenerating cysts, anti-convulsant therapy may be withdrawn when the lesion disappears and the EEG is normal. In those patients with calcified or viable parasites, anticonvulsant therapy should be continued for a 1-year seizure-free interval.
Neurosurgical resection is used as a last resort for lesions causing significant neurologic impairment. Resolution of lesions with medical management alone is superior, and the reliance on surgical intervention has decreased over time. Less invasive, neuroendoscopic resection has been used for removal of protracted lesions. Brain biopsy should be considered in cases in which the diagnosis remains questionable and the lesion has not resolved.
CNS-imaging studies should be repeated at 2-month intervals (with continued therapy) until the parenchymal brain cysticerci are successfully eliminated. The outcome for neurocysticercosis is generally good. The majority of patients weaned from anticonvulsants remain seizure free. However, there is a 10% mortality with neurocysticercosis, and others may have recurrent seizures or deterioration of higher cerebral functions.
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