Approach to the International Traveler With Neurological Symptoms

Kiran T Thakur; Joseph R Zunt


Future Neurology. 2015;10(2):101-113. 

In This Article

Confusion &/or Seizures

One of the most feared neurological complications in a returning traveler is severe malaria, which can cause confusion, seizures, coma and death. History elicited from the patient should include details regarding preventative measures taken, including use of malaria prophylaxis, bednets, protective clothing and repellents. According to the CDC's 2011 malaria surveillance report, the number of malaria cases reported in the USA was the highest since 1971, representing a 14% increase from 2010 and a 48% increase from 2008.[45] Among the 929 cases in US civilians for whom information on chemoprophylaxis use was defined, only 57 (6%) patients reported they had adhered to a chemoprophylactic drug regimen. Among the 1925 reported cases, 275 (14%) were classified as severe malaria, including five patients who died.[45] Malaria is typically a serious disease with high risk of death for travelers with no prior exposure to malaria. Travelers who become ill with fever or flu-like symptoms while traveling in a malaria-endemic area or after returning home should seek immediate medical attention. Neurological symptoms are often seen in parallel with multi-organ dysfunction. Therefore, workup should include close monitoring of vital signs with frequent glucose checks, laboratory evaluation with complete blood count (CBC) to monitor for thrombocytopenia and anemia, complete metabolic panel (CMP), serial lactate levels, thick and thin blood films and serial parasite counts. CSF analysis is important for ruling out other conditions, including bacterial meningitis.[46] Given the potential for cerebral edema and herniation, patients with suspected malaria who are confused or comatose should ideally have neuroimaging performed to determine if LP is safe. Given the high occurrence of seizures, electroencephalography, when available, should be done in patients with confusion or coma. Neurocognitive dysfunction and epilepsy are potential long-term sequelae that have been reported in travelers with history of malaria and should be considered in the differential diagnosis of patients with remote severe malarial illness presenting with neurological symptoms.

Human African trypanosomiasis (HAT) caused by an extracellular protozoan parasite belonging to the genus Trypanosoma, should be considered in the encephalopathic patient returning from Central or West Africa. Two Trypanosoma brucei subspecies (T.b.), T.b. gambiense and T.b. rhodesiense, are transmitted via a bite from a Tsetse fly. HAT due to T.b. gambiense is rare among travelers, though has been sporadically reported in immigrants and long-term Caucasian residents living in rural settings.[47–49] The symptomatology in travelers is markedly different from the classic descriptions of African HAT patients. The classical sleep disorders and neurological findings of HAT are not a hallmark in travelers though patients may present with movement disorders, severe headaches or mild insomnia.[50] The trypanosomal chancre at the site of the infective tsetse bite, typical for T.b. rhodesiense infection, is commonly seen in travelers and is an important diagnostic clue, as is evidence of laterocervical lymphadenopathy or Winterbottom sign (Table 2).[51] As the disease progresses, travelers may become severely ill with cognitive decline, lethargy and urinary and fecal incontinence, followed by coma, multi-organ failure and death. Diagnosis can be made by examination for parasites on wet blood film, indirect immunofluorescence or polymerase chain reaction (PCR) testing. Cases of HAT have been documented in Europe and the USA, usually in travelers who have recently returned from east or west Africa. A review noted 94 cases between 2000 and 2010 that were reported in 19 nonendemic regions. Seventy-two percent of them corresponded to the Rhodesiense form, whereas 28% corresponded to the Gambiense in travelers who have recently returned from east Africa.[52] In another study, HAT was reported in 83 travelers in nonendemic, mostly European, countries.[53]

In the critically ill patient with evidence of a cerebrovascular event and systemic shock, viral hemorrhagic fever (VHF) should be considered if travel included tropical regions. VHF refers to a group of highly virulent illnesses caused by four families of viruses: Arenaviridae, Filoviridae, Bunyaviridae and Flaviviridae. In general, these conditions commonly begin as a febrile prodrome with myalgias, accompanied in some cases by gastrointestinal symptoms and sore throat. Patients typically present in the country where exposure occurred, as they rapidly develop hemodynamic instability during the early stages of infection, manifested by mild hypotension and shock as infection advances. Diffuse petechial hemorrhage involving the skin and mucous membranes provides an additional clue to diagnosis (Table 2). Some of the viruses causing hemorrhagic fever rarely produce neurological symptoms, including Lassa, Argentine hemorrhagic fever, Dengue, Marburg, Rift Valley Fever, Hantavirus and Puumala virus.[54] Lassa hemorrhagic fever has been associated with seizures, movement disorders, and ataxia that can overlap or follow the onset of hemorrhagic fever.[55] Rift Valley fever is associated with encephalitis and retinal vasculitis.[56] Hemorrhagic fever with renal syndrome (HFRS) caused by Puumala virus is commonly associated with headache and blurred vision, while a small proportion of patients develop severe neurological manifestations including intracerebral hemorrhage (ICH) and seizures.[57] Dengue virus infection can present with a variety of neurological manifestations, and in 2009, the WHO established a new case classification system which includes CNS involvement.[58,59] Among travelers, dengue is a common disease, particularly in those traveling through Asia and Central and South America; in a cohort of 1207 short-term travelers from The Netherlands, the incidence of symptomatic dengue virus infection was four cases per 1000 adults.[58,60] Dengue fever has been diagnosed in an increasing proportion of febrile travelers returning from the tropics, ranging from 2% in the early 1990s to 16% in the last decade.[61–64] In some case series, dengue fever has been reported as the second most frequent cause of hospitalization (after malaria) among travelers returning from the tropics.[65–67] The true incidence of neurological manifestations of dengue are unknown. Fever, severe headache, muscle, bone, joint and abdominal pain may develop prior to the onset of depressed mental status. History of a mild transient skin rash can arise early in infection and is an important diagnostic clue (Table 3). Dengue encephalopathy, the most common neurological manifestation, often occurs in the setting of prolonged hypovolemic shock, metabolic disturbances or hepatic or kidney failure.[68] Dengue encephalitis is a rare complication of infection, with less than 1% of patients developing CNS infection.[69] In patients presenting with altered mental status and a clinical suspicion of dengue, CSF analysis include assays to detect the nonstructural protein 1 antigen, PCR and dengue-specific IgM antibodies, though many are not easily available in many endemic regions.

While neurocystercercosis (NCC) is the most common helminthic infection of the CNS and a major cause of acquired epilepsy worldwide, NCC has been infrequently described in returning travelers, though should be strongly considered in an immigrant from an endemic region.[70] CNS manifestations occur when Taenia solium parasites lodge in the brain parenchyma, subarachnoid space, ventricular system or spinal cord. In a meta-analysis of NCC cases, the condition was rarely reported in returning travelers, with most patients developing symptoms at least 2 years after returning home.[71] In returning travelers, seizures were the most common clinical manifestation of the disease, with most patients having evidence of parenchymal NCC.[71]