The n e w e ng l a n d j o u r na l
Case Records of the Massachusetts General Hospital
From the Departments of Medicine
(K.C.Z., R.C.L.), Radiology (R.G.G.), and
Pathology (J.A.B.), Massachusetts Gen‑
eral Hospital, and the Departments of
Medicine (K.C.Z., R.C.L.), Radiology
(R.G.G.), and Pathology (J.A.B.), Harvard
Medical School — both in Boston.
N Engl J Med 2019;380:380-7.
DOI: 10.1056/NEJMcpc1815528
Copyright © 2019 Massachusetts Medical Society.
380
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of m e dic i n e
Founded by Richard C. Cabot
Eric S. Rosenberg, M.D., Editor
Virginia M. Pierce, M.D., David M. Dudzinski, M.D., Meridale V. Baggett, M.D.,
Dennis C. Sgroi, M.D., Jo‑Anne O. Shepard, M.D., Associate Editors
Alyssa Y. Castillo, M.D., Case Records Editorial Fellow
Emily K. McDonald, Sally H. Ebeling, Production Editors
Case 3-2019: A 70-Year-Old Woman with Fever,
Headache, and Progressive Encephalopathy
Kimon C. Zachary, M.D., Regina C. LaRocque, M.D., M.P.H.,
R. Gilberto Gonzalez, M.D., Ph.D., and John A. Branda, M.D.​​
Pr e sen tat ion of C a se
Dr. John I. Hogan (Medicine): A 70-year-old woman with a history of migraines was
admitted to this hospital in the fall because of fever, headache, and progressive
encephalopathy.
The patient had been in her usual state of health until 12 days before this ad-
mission, when fevers with temperatures as high as 39.7°C developed, along with
chills, fatigue, weakness, and headache. The patient also had nausea and intermit-
tent episodes of vomiting. She took acetaminophen and sumatriptan, but the symp-
toms persisted. On the sixth day of illness, she was seen by her primary care
physician. A rapid influenza test was negative, and the results of urinalysis were
reportedly normal; a blood sample was sent to the laboratory for testing for Borrelia
burgdorferi antibodies.
The following day, the patient was seen in the emergency department at an-
other hospital for further evaluation. On examination, she was febrile and ap-
peared ill. The platelet count, prothrombin-time international normalized ratio,
anion gap, and blood levels of electrolytes and lactate were normal, as were the
results of renal-function tests and urinalysis; other laboratory test results are
shown in Table 1. Blood and urine specimens were sent for culture. A chest radio-
graph was normal. A lumbar puncture was performed; the results of cerebrospinal
fluid (CSF) analysis are shown in Table 1. Vancomycin and piperacillin–tazobactam
were administered intravenously, and admission to the hospital was recommended.
The patient declined admission and was discharged home with a prescription for
oral doxycycline.
During the next 2 days, fevers persisted, and the patient became progressively
less interactive. She got out of bed infrequently; she had an unsteady gait and
needed assistance to walk. Oral intake decreased, frequency of urination in-
creased, and tremulousness of the arms and jaw developed. On the ninth day of
illness (4 days before this admission), the patient’s family again took her to the
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 Case Records of the Massachuset ts Gener al Hospital

Table 1. Laboratory Data.*

6 Days before 4 Days before

Reference Range, Current Admission, Current Admission, Reference Range, On Admission,
Variable Other Hospital Other Hospital Other Hospital This Hospital† This Hospital
Blood
Hemoglobin (g/dl) 11.8–15.8 11.6 10.8 12.0–16.0 12.6
Hematocrit (%) 35.0–47.0 34.7 32.5 36.0–46.0 36.6
White-cell count (per mm3) 4200–10,200 8600 8200 4500–11,000 9300
Differential count (%)
Neutrophils 47–80 88
Immature granulocytes <1 1
Lymphocytes 14–46 7
Monocytes 5–12 5
Eosinophils 0–5 0
Basophils 0–2 0
Glucose (mg/dl) 70–99 114 115 70–110 116
Cerebrospinal fluid
Color Colorless Colorless
Turbidity Clear Slight
Xanthochromia None None
3)
Red-cell count (per mm 579 0–5 17
Total nucleated-cell count (per mm3) 9 0–5 73
Differential count (%)
Neutrophils 11 0 1
Lymphocytes 76 0–100 89
Monocytes 13 0–100 10
Protein (g/dl) 61 5–55 117
Glucose (mg/dl) 63 50–75 52
Gram’s stain 1+ Polymorphonu‑ A few mononuclear
clear leukocytes, cells, no organisms
no organisms

* To convert the values for glucose to millimoles per liter, multiply by 0.05551.
† Reference values are affected by many variables, including the patient population and the laboratory methods used. The ranges used at Massa­
chusetts General Hospital are for adults who are not pregnant and do not have medical conditions that could affect the results. They may
therefore not be appropriate for all patients.

emergency department at the other hospital.
On examination, the patient appeared uncom-
fortable and ill and was trembling. She was alert
and oriented, followed commands, and respond-
ed to questions with single-word answers. The
temperature was 39.4°C; the other vital signs
were normal. The oral mucous membranes ap-
peared dry. The platelet count, anion gap, venous
blood gas measurements, and blood levels of
electrolytes, lactate, and ammonia were normal,
as were the results of renal-function tests, liver-
function tests, and urinalysis; other laboratory
test results are shown in Table 1. The test for
B. burgdorferi antibodies (for which a sample had
been sent 3 days earlier) was negative, as were
the blood and urine cultures (for which samples
had been sent 2 days earlier). Blood specimens
were obtained, and imaging studies were per-
formed.
Results of computed tomography (CT) of the

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 The n e w e ng l a n d j o u r na l
head, performed after the intravenous adminis-
tration of contrast material, were normal. CT of
the abdomen and pelvis, performed after the
intravenous administration of contrast material,
revealed trace bilateral pleural effusions, four in-
determinate lesions (8 to 20 mm in diameter)
in the liver, a nonobstructive calculus (2 mm in
diameter) in the lower pole of the left kidney,
subcentimeter hypodensities in both kidneys,
trace free fluid in the pelvis, diffuse atheroscle-
rotic calcifications in the aorta and its visualized
branches, colonic diverticula, and degenerative
changes of the bony skeleton.
A bolus of normal saline was administered
intravenously, and the patient was admitted to
the other hospital. Acyclovir, ceftriaxone, vanco-
mycin, ampicillin, acetaminophen, and intrave-
nous fluids were administered. During the next
3 days, intermittent fevers with temperatures as
high as 38.4°C continued, and the patient be-
came disoriented and then mute. She was no
longer able to follow commands. Urinary reten-
tion, lead-pipe muscular rigidity in the arms and
legs, increased deep-tendon reflexes, and nuchal
rigidity with passive flexion developed. Polymerase-
chain-reaction (PCR) assays for herpes simplex
virus DNA and enterovirus RNA, performed on
the CSF sample obtained during the first emer-
gency department visit, were negative. The eryth-
rocyte sedimentation rate and blood levels of C3,
C4, thyrotropin, folate, and vitamin B12 were nor-
mal, and blood tests for human immunodeficiency
virus antibodies, Treponema pallidum antibodies,
cryptococcal antigen, Anaplasma phagocytophilum
DNA, babesia species DNA, antinuclear antibod-
ies, and β2-glycoprotein antibodies were negative.
An electrocardiogram and transthoracic echo-
cardiogram were normal. Magnetic resonance
imaging (MRI) of the head, performed after the
intravenous administration of contrast material,
reportedly revealed diffuse abnormal meningeal
enhancement that was most notable in the cere-
bellum. Acyclovir was discontinued.
On the fourth hospital day, the patient had a
2-minute episode during which the eyes rolled
upward and the arms and legs stiffened. Loraze-
pam and levetiracetam were administered. Electro-
encephalography that was performed after the
event revealed generalized slowing. The patient was
transferred to this hospital for further treatment.
On admission, additional history was obtained
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of m e dic i n e
from the patient’s family. The patient had had
mild cognitive decline during the past year, and
her son had begun assisting with management
of her finances. Approximately 3 weeks before
the onset of illness, the patient had noticed a
dime-sized erythematous lesion on the right
shoulder and thought it might have resulted
from an insect bite. During the week before the
onset of illness, she had been seen by a dentist
for an unspecified treatment and had taken
clindamycin for 2 days. She had a history of
migraines, fibromyalgia, depression, and anxiety,
and in the remote past she had undergone chole-
cystectomy, hysterectomy, and treatment for Lyme
disease. Her medications included citalopram and
sumatriptan; she had no known allergies. She
lived with her husband, two adult children, and
pet dogs and cats near a horse farm in a wood-
ed area of northern New England. She enjoyed
spending time outdoors and frequently removed
ticks from her pets. She did not smoke tobacco
or use illicit drugs, and she drank alcohol rarely.
There was a family history of Alzheimer’s disease
and stroke.
On examination, the vital signs were normal.
The patient was somnolent, nonverbal, and un-
able to follow commands. She intermittently
opened her eyes in response to a loud voice and
tracked the examiner with conjugate gaze. There
was no movement of the arms after application
of pressure to the beds of the fingernails; triple
flexion occurred after application of pressure to
the beds of the toenails. Deep-tendon reflexes
in the arms and legs were brisk. Nuchal rigidity
was present. There was a systolic ejection mur-
mur (grade 2/6) at the left sternal border. The
remainder of the general physical examination
was normal. The red-cell indexes, platelet count,
prothrombin time, partial-thromboplastin time,
anion gap, and blood levels of electrolytes were
normal, as were the results of renal-function and
liver-function tests; other laboratory test results
are shown in Table 1. A lumbar puncture was
performed, with an opening pressure of 18 cm
of water; the results of CSF analysis are shown
in Table 1.
Dr. R. Gilberto Gonzalez: MRI of the head (Fig. 1)
revealed findings consistent with progressive
meningoencephalitis. The findings were most
prominent in the cerebellar hemispheres and were
more severe on the left side than on the right
 Case Records of the Massachuset ts Gener al Hospital

side. There was associated edema in the cerebel-
lar hemispheres. As compared with the previous
MRI study, this study showed an increase in ef-
facement involving the fourth ventricle and an
increase in the size of the lateral and third ven-
tricles, findings suggestive of early obstructive
hydrocephalus. Results of magnetic resonance
angiography of the head and neck were normal.
Dr. Hogan: A diagnostic test was performed.
Differ en t i a l Di agnosis
Dr. Kimon C. Zachary: This 70-year-old woman was,
to the best of our knowledge, immunocompetent
aside from her age. She presented in autumn
with an acute febrile illness, with headache and
progressive neurologic signs and symptoms, in-
cluding depressed sensorium, nuchal rigidity, gait
ataxia, parkinsonism, hyperreflexia, and a pos-
sible seizure. The information provided suggests
that she has a syndrome of acute meningoen-
cephalitis, with inflammation of the meninges
and brain parenchyma. The differential diagno-
sis is quite expansive, including noninfectious
entities and many infectious diseases.
presence of multifocal encephalitis. In contrast,
central nervous system (CNS) infection with Liste-
ria monocytogenes is a strong consideration. Liste-
ria meningitis occurs primarily in immunocom-
promised hosts or persons older than 50 years of
age, can develop in a less-than-fulminant man-
ner, and can be associated with a CSF white-cell
count of less than 1000 per cubic millimeter;
these features are compatible with this patient’s
presentation. Encephalitis due to listeria infection
usually has brain-stem involvement (rhomben-
cephalitis), which was not present in this patient.
Given the patient’s environmental exposures,
tickborne bacterial infections should also be con-
sidered. Rocky Mountain spotted fever, which is
due to Rickettsia rickettsii, is uncommon in New
England. Rocky Mountain spotted fever causes
an acute febrile illness, usually with a prominent
headache, and also causes an endothelial vascu-

Noninfectious Causes
Although this patient was not known to have a
malignant tumor, paraneoplastic encephalitis
merits consideration. Patients with paraneoplas-
tic encephalitis usually have involvement of the
limbic system or brain stem or present with a
more generalized encephalomyelitis; this pa-
tient’s illness did not fit any of these patterns.
Given the prominent involvement of the cere-
bellum, paraneoplastic cerebellar degeneration
should be considered, but this disorder would
not cause an acute febrile illness with meningitis
and evidence of encephalitis outside the cerebel-
lum. Autoimmune encephalitis is rare; the most
common and best characterized type is anti–N-
Figure 1. MRI of the Head.
methyl-d-aspartate (NMDA) receptor encephalitis.
A T2-weighted image of the posterior fossa shows find‑
This entity appears almost exclusively in young ings consistent with progressive meningoencephalitis.
adults and children and is very rare in persons The findings are most prominent in the cerebellar hemi‑
older than 50 years of age. spheres and are more severe on the left side than on
the right side. There is associated edema in the cere‑
Bacterial Infections bellar hemispheres. As compared with the previous MRI
study, this study shows an increase in effacement involv‑
Pyogenic bacterial meningitis from Streptococcus ing the fourth ventricle and an increase in the size of the
pneumoniae, Neisseria meningitidis, or Haemophilus lateral and third ventricles, findings suggestive of early
influenzae can be ruled out in this patient, given obstructive hydrocephalus.
the pace of the illness, the CSF profile, and the

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 The n e w e ng l a n d j o u r na l
litis, which can lead to brain disease. Early treat-
ment with doxycycline greatly lowers morbidity
and mortality. Rash is often absent in the first
3 or 4 days of the illness but would have been
present by the time this patient presented to this
hospital, on day 13 of her illness.
Anaplasmosis, which is due to A. phagocyto-
philum, is common in New England and is trans-
mitted by Ixodes scapularis, the black-legged deer
tick. Patients with anaplasmosis typically present
with an acute febrile illness, often with a head-
ache. This patient had a negative PCR assay for
this infection, although this result does not rule
out the diagnosis. However, encephalitis is rare
in patients with anaplasmosis, and the hallmark
laboratory abnormalities — namely leukopenia,
thrombocytopenia, and elevated aminotransfer-
ase levels — were not seen in this case.
Lyme disease, which is due to B. burgdorferi, is
a well-known cause of aseptic meningitis and of
cranial and radicular neuritis, manifestations
that occur in the early disseminated stage of in-
fection. However, encephalitis is rare in patients
with neuroborreliosis, and testing for Lyme anti-
bodies, which is usually positive in the context of
neuroinvasive disease, was negative in this case.
Infection with B. miyamotoi, a spirochete that
is more closely related to B. hermsii (an agent of
relapsing fever) than to B. burgdorferi, is an
emerging cause of human disease in the north-
eastern United States. The most common clini-
cal presentation resembles that of anaplasmosis,
including similar laboratory abnormalities, which
were absent in this case.1 An association be-
tween B. miyamotoi infection and meningoen-
cephalitis has been described, albeit in immuno-
compromised persons.2
This patient’s frequent exposure to animals
raises the possibility of leptospirosis, which is
transmitted by means of exposure to contami-
nated animal urine. Aseptic meningitis is a com-
mon feature of this illness, but encephalitis is
rare, and the patient’s normal renal and hepatic
laboratory values argue against this infection.
Bartonella henselae infection, which is transmitted
by cats or their fleas, can be associated with en-
cephalopathy or encephalitis, although well-doc-
umented cases of CNS invasion are very rare.3
Respiratory tract infection with Mycoplasma
pneumoniae can be complicated by CNS disease.
However, most cases occur in children and
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of m e dic i n e
young adults, and no antecedent respiratory ill-
ness was reported in this patient. Mycobacterium
tuberculosis infection can cause a gradual onset of
meningitis, which is usually most prominent at
the skull base, and can also cause tubercular
abscesses of the brain. The findings in this pa-
tient would be highly atypical of tuberculosis,
and no epidemiologic risk factors for this dis-
ease were reported.
Fungal Infections
Cryptococcus neoformans infection is a well-known
and widely distributed cause of meningoencepha-
litis that usually occurs in patients with compro-
mised cell-mediated immunity; the occurrence
of C. neoformans infection in immunocompetent
persons has been well described but is rare. In
comparison, C. gattii infection is more likely to
develop in immunocompetent persons, but it is
not known to occur in New England. Further-
more, cryptococcal antigen was not detected in
the patient’s blood. Histoplasma capsulatum infec-
tion is uncommon in New England and rarely
causes meningoencephalitis. This patient did
not have any epidemiologic risk factors for other
geographically restricted endemic mycoses, such
as Coccidioides immitis infection, a well-known
cause of CNS disease.
Protozoa
On rare occasion, certain free-living amebas can
cause meningoencephalitis. Naegleria fowleri is
found in bodies of fresh water, typically in climates
warmer than that of northern New England.
This ameba can invade the meninges and brain
by means of nasal inoculation while the host is
submerged in contaminated water, thereby caus-
ing a fulminant infection with a dismal progno-
sis. This patient did not have a plausible expo-
sure, so this disease is unlikely. Acanthamoeba
and balamuthia species are protozoa that are
present ubiquitously in the environment. These
organisms can cause a gradual onset of meningo-
encephalitis that is known as granulomatous
amebic encephalitis, but the disease occurs
primarily in immunocompromised persons and
therefore is unlikely in this case.
Viruses
As a group, viruses are the most commonly iden-
tified cause of acute encephalitis and meningo-
 Case Records of the Massachuset ts Gener al Hospital
encephalitis. Herpes simplex virus is the most
commonly identified cause of viral encephalitis
in the United States. Because early treatment
with intravenous acyclovir lowers morbidity and
mortality, prompt consideration of herpes sim-
plex virus is of critical importance. In herpes
simplex encephalitis, a temporal lobe is typically
involved, which was not the case in this patient,
and concomitant meningitis is unusual. The CSF
PCR assay for herpes simplex virus DNA is
highly sensitive and specific. The test can be
negative very early in the course of illness but
should be positive by day 7; this patient had a
negative test on day 7 of her illness.
Reactivation of varicella–zoster virus can cause
CNS vasculopathy, which results in a strokelike
syndrome. This often occurs after a typical erup-
tion of herpes zoster, particularly herpes zoster
ophthalmicus. A more diffuse reactivation that
involves multiple small intracerebral arteries can
develop, but it usually occurs in immunocom-
promised persons. This patient’s imaging stud-
ies were not suggestive of vasculitis.
Rabies should be considered in a case of en-
cephalitis of unknown origin. A relevant animal
exposure was not described in this case, although
it could have been occult, particularly if bats
were present in the patient’s rural home. How-
ever, her clinical presentation did not include the
hydrophobia, pharyngeal spasms, or agitation
that are seen in encephalitic (“furious”) rabies or
the ascending paralysis that is seen in paralytic
(“dumb”) rabies.
Given the patient’s home environment, expo-
sure to the excreta of mice is also possible and
would confer a predisposition to infection with
lymphocytic choriomeningitis virus. This viral
infection often causes leukopenia and thrombo-
cytopenia, which were absent in this case, and
rarely causes encephalitis. In the summer and
autumn, enteroviruses are common causes of
aseptic meningitis and occasionally cause en-
cephalitis. In this patient, a CSF PCR assay was
negative for enterovirus RNA.
Arthropod-Borne Viruses (Arboviruses)
Eastern equine encephalitis virus and West Nile
virus are both present in New England; these
viruses are amplified in birds and transmitted by
mosquitoes. Eastern equine encephalitis virus
has been a sporadic cause of human encephalitis
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in states along the Atlantic coast, with cases re-
ported in the mid-to-late summer in New England.
Although this viral infection is still rare, with
5 to 15 cases reported to the Centers for Disease
Control and Prevention (CDC) annually, more
cases have been reported in northern states in
recent years, including 9 cases in northern New
England from 2007 to 2016.4 Eastern equine
encephalitis virus infection is typically associated
with leukocytosis in peripheral blood and pleo-
cytosis in CSF, with a white-cell count ranging
from 500 to 2000 per cubic millimeter, a higher
count than that seen in this case. Involvement of
the basal ganglia and thalamus is common.5
West Nile virus has been by far the most com-
mon neuroinvasive arbovirus in the United States,
with approximately 1300 cases reported to the
CDC in 2016 and again in 2017. However, rela-
tively few cases have been reported in northern
New England (7 cases from 2013 to 2016).4 Mild
leukocytosis in peripheral blood is sometimes
present, and pleocytosis in CSF is associated
with a white-cell count of less than 500 per cubic
millimeter. Parkinsonism and evidence of basal
ganglia involvement are common.6
Similar to West Nile virus, Powassan virus is
a flavivirus, but it is transmitted by the I. scapu-
laris tick and maintained in a rodent reservoir.
Until recent years, this viral infection was very
rare in New England, with no cases reported to
the CDC in most years. However, 5 cases in
northern New England and 13 cases in Massa-
chusetts were reported from 2013 to 2016.4 The
clinical spectrum associated with Powassan virus
encephalitis is similar to that associated with
eastern equine encephalitis virus infection and
West Nile virus infection. Results of routine
laboratory studies are typically normal, and the
CSF white-cell count is usually less than 1000 per
cubic millimeter. Parkinsonism and involvement
of the basal ganglia and thalamus are common.7,8
This patient has a clinical syndrome that is
compatible with infection with eastern equine
encephalitis virus, West Nile virus, or Powassan
virus. The normal white-cell count in peripheral
blood and relatively modest pleocytosis in CSF
argue against eastern equine encephalitis virus.
The incubation period for West Nile Virus neuro-
invasive disease is approximately 2 to 14 days;
we know that the patient became ill during au-
tumn and that mosquito activity declines with
385
 The n e w e ng l a n d j o u r na l
cooler weather, usually ending after a hard frost.
However, ticks remain active well into autumn,
even in northern New England. Therefore, the
patient’s infection was more likely to have been
transmitted by a tick than by a mosquito, which
makes Powassan virus infection the most likely
diagnosis in this case. To establish the diagno-
sis, I would perform a CSF test for Powassan
virus IgM antibodies.
Dr . K imon C . Z ach a r y ’s Di agnosis
Powassan virus meningoencephalitis.
Pathol o gic a l Discussion
Dr. John A. Branda: Several tests for vectorborne
agents of viral encephalitis were performed. Se-
rum tests for West Nile virus IgM and IgG anti-
bodies were negative, as was a CSF PCR assay for
West Nile virus RNA. CSF tests for IgM anti-
bodies to West Nile virus, St. Louis encephalitis
virus, and eastern equine encephalitis virus were
also negative. However, a CSF test for Powassan
virus IgM antibodies was positive, as was the
more specific plaque reduction neutralization
test, at a CSF titer of 1:4. In the context of the
clinical findings, these results establish the di-
agnosis of Powassan virus encephalitis.
Powassan virus can be challenging to diag-
nose, because direct detection of the virus in
blood or CSF with PCR assays or culture tech-
niques is typically possible only during the pro-
dromal phase of illness.9 During this phase,
patients may not seek clinical attention, and if
they do, there may be no reason to suspect Pow-
assan virus infection. Once the illness enters the
encephalitic phase, viremia is often undetectable
and the diagnosis usually relies on antibody
testing.9 In the first days or weeks of encephali-
tis, it is usually possible to detect only an IgM
antibody response. This presents a challenge,
because first-line tests for Powassan virus IgM
antibodies, such as enzyme-linked immunosor-
bent assays or similar immunoassays, are more
likely to produce false positive results than tests
for Powassan virus IgG antibodies. The false
positive results are mainly caused by cross-reac-
tivity with antibodies directed against other flavi-
viruses. A positive serum or CSF test for Powas-
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of m e dic i n e
san virus IgM antibodies should be confirmed
with a test for neutralizing antibodies, such as
the plaque reduction neutralization test or a
similar assay.10 When Powassan virus infection
is suspected, consultation with a public health
laboratory is recommended for assistance with
choosing the appropriate diagnostic tests.
Dr. Virginia M. Pierce (Pathology): Dr. LaRocque,
why is the incidence of Powassan virus infection
increasing in New England?
Dr. Regina C. LaRocque: A variety of factors in-
fluence the epidemiology of tickborne illnesses.
Human behaviors such as land use, cultural
habits, and health care reporting are important
determinants, as is population-level immunity.
Weather also affects the distribution and sea-
sonality of tickborne illnesses. Models show that
the geographic and annual variation in the tim-
ing of human Lyme disease can be predicted by
temperature, precipitation, and humidity.11
There is widespread scientific consensus that
human activities are changing the world climate,
resulting in more variable weather, heat waves,
heavy precipitation events, and more intense
storms.12 In a 2016 report, the U.S. Global
Change Research Program predicted that climate
change would interact with other factors to re-
sult in an overall increase in tickborne illnesses,
by means of altered geographic distribution, ear-
lier seasonal tick activity, and the emergence or
reemergence of pathogens.13 In fact, the number
of cases of tickborne bacterial and protozoan
diseases reported to the CDC increased from
approximately 22,000 in 2004 to more than
48,000 in 2016.14
Consequently, clinicians are on the front line
in responding to the effect of climate change on
the health of individual patients and communi-
ties, and they should be prepared to counsel pa-
tients about steps to mitigate risk. For example,
patients can lower their risk of tickborne ill-
nesses by using insect repellents, wearing long-
sleeved shirts and pants, avoiding bushy and
wooded areas, and performing thorough tick
checks after spending time outdoors.
Dr. Hogan: This patient had a monthlong hos-
pital course, which was complicated by delirium,
clinically significant parkinsonism, and poor
oral intake, which led to placement of a gastros-
tomy tube. Over the course of several weeks, her
 Case Records of the Massachuset ts Gener al Hospital

mental status gradually improved. She regained Fina l Di agnosis

the ability to walk and was ultimately trans-
ferred to a rehabilitation hospital. Over time, her Powassan virus encephalitis.
motor skills and overall state of health contin-
This case was presented at the Harvard Medical School post-
ued to improve, and the abnormal findings on graduate course, “Infectious Diseases in Adults 2018,” directed
imaging studies diminished. by Nesli O. Basgoz, M.D., Sandy Bliss-Nelson, M.D., Rajesh T.
Fourteen months after discharge, at the most Gandhi, M.D., and Rochelle Walensky, M.D., M.P.H.
Dr. Branda reports receiving grant support from Immunetics,
recent follow-up appointment, the patient still Alere, bioMérieux, and Zeus Pharmaceuticals, grant support and
had a shuffling gait and some parkinsonism. consulting fees from DiaSorin, and consulting fees from T2
She had a mild sensation of disequilibrium and Biosystems. No other potential conflict of interest relevant to
this article was reported.
some mild cognitive deficits, but her overall Disclosure forms provided by the authors are available at
condition has continued to slowly improve with NEJM.org.
supportive care.

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