NEJMcpc2309349

The n e w e ng l a n d j o u r na l of m e dic i n e
Case Records of the Massachusetts General Hospital
Founded by Richard C. Cabot

Eric S. Rosenberg, M.D., Editor
David M. Dudzinski, M.D., Meridale V. Baggett, M.D., Kathy M. Tran, M.D.,
Dennis C. Sgroi, M.D., Jo‑Anne O. Shepard, M.D., Associate Editors
Emily K. McDonald, Tara Corpuz, Production Editors
Case 38-2023: A 68-Year-Old Woman

with Abnormal Movements and Confusion
Bart K. Chwalisz, M.D., Hillary R. Kelly, M.D., Alice W. Flaherty, M.D., Ph.D.,
April M. Jorge, M.D., and Mandakolathur R. Murali, M.D.
Pr e sen tat ion of C a se
Dr. D. Curtis Wegener (Neurology): A 68-year-old woman was admitted to this hospital From the Departments of Neurology
because of worsening confusion and abnormal movements of the face, arms, and legs. (B.K.C., A.W.F.), Radiology (H.R.K.), Psy‑
chiatry (A.W.F.), Medicine (A.M.J.,
The patient had been in her usual state of health until 9 weeks before the cur- M.R.M.), and Pathology (M.R.M.), Mas‑
rent presentation, when she presented to another hospital because of intermittent sachusetts General Hospital, the Depart‑
slurred speech and dizziness that had lasted for 1 day. The score on the National ments of Neurology (B.K.C., A.W.F.), Ra‑
diology (H.R.K.), Psychiatry (A.W.F.),
Institutes of Health Stroke Scale (NIHSS) was obtained; the NIHSS is an 11-com- Medicine (A.M.J., M.R.M.), and Patholo‑
ponent tool that assesses the severity of stroke, with scores ranging from 0 to 42 gy (M.R.M.), Harvard Medical School,
and higher scores indicating more severe neurologic deficits. Her NIHSS score was and the Department of Radiology, Massa‑
chusetts Eye and Ear (H.R.K.) — all in
1 owing to the presence of mild-to-moderate dysarthria, and she was not consid- Boston.
ered to be a candidate for treatment with intravenous tissue plasminogen activator.
N Engl J Med 2023;389:2277-85.
Imaging studies were obtained. DOI: 10.1056/NEJMcpc2309349
Magnetic resonance imaging (MRI) of the head, performed without the admin- Copyright © 2023 Massachusetts Medical Society.
istration of intravenous contrast material, reportedly revealed a punctate focus of
CME
restricted diffusion associated with mild signal hyperintensity involving the deep at NEJM.org
white matter of the left frontal lobe on T2-weighted and fluid-attenuated inversion
recovery (FLAIR) imaging. This finding was consistent with an acute ischemic
infarct without hemorrhage or mass effect. There were also findings that had been
observed on previous imaging, including foci of encephalomalacia in the right
inferior frontal lobe and left occipital lobe that were related to previous trauma, a
punctate old lacunar infarct in the inferior left cerebellar hemisphere, and super-
imposed patchy foci of T2-weighted and FLAIR white-matter hyperintensity most
consistent with small-vessel disease. Magnetic resonance angiography of the head
and neck reportedly showed no intracranial or cervical occlusion, high-grade ste-
nosis, or aneurysm. The patient was admitted to the hospital.
The patient had been taking apixaban daily because of a history of two deep
venous thromboses, and the treatment was continued. She had also been taking
atorvastatin for hyperlipidemia, and the dose was increased. Transthoracic echo-
cardiography showed a normal left ventricular ejection fraction and no patent
n engl j med 389;24 nejm.org December 14, 2023 2277

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No other uses without permission. Copyright © 2023 Massachusetts Medical Society. All rights reserved.
foramen ovale. Continuous telemetric monitor- racetam was increased. EEG reportedly showed
ing showed no evidence of atrial fibrillation. excessive irregular background slow-wave activ-
Mobile cardiac telemetry was planned for the ity without focal, lateralizing, or epileptiform
30-day period after discharge. features; there were no findings that correlated
On the second hospital day, frequent irregu- to the movements of the head and body. On the
lar movements of the right leg developed, occur- fifth hospital day, the irregular movements had
ring every few seconds in a nonrhythmic pat- not abated, and treatment with levetiracetam
tern. The next day, similar movements of the was stopped. Treatment with low-dose clonaze-
right arm developed. The patient described the pam at bedtime was started to help with sleep.
movements as involuntary and reported no uncon- On the sixth hospital day, the patient was dis-
trollable urges or compulsions to move the arm charged to a rehabilitation facility.
or leg. Computed tomography (CT) of the head, Three days after discharge, a family member
performed without the administration of intra- observed that the patient was confused and un-
venous contrast material, was reportedly nega- able to maintain a conversation. The family
tive for any new findings. Electroencephalogra- member brought her to the emergency depart-
phy (EEG) was reportedly normal in the waking, ment of this hospital for evaluation. In the emer-
drowsy, and light-sleep states. The dysarthria re- gency department, the patient was not able to
solved, but the involuntary movements persisted. provide additional information. Other medical
The patient was discharged home on the seventh history, obtained from the family member, in-
hospital day. cluded hypothyroidism, hypertension, diabetes
During the next 6 weeks, involuntary move- mellitus, hyperlipidemia, pulmonary hyperten-
ments involving the arms, legs, and tongue oc- sion, and vitiligo.
curred with increasing frequency. The patient Medications included ambrisentan, apixaban,
began using a walker. Nine days before the cur- atorvastatin, cholecalciferol, glipizide, levothy-
rent presentation, the patient was again admit- roxine, metformin, omeprazole, and sitagliptin.
ted to the other hospital after multiple falls at Clonazepam had not been administered at the
home, which she attributed to uncontrolled rehabilitation facility. The patient had taken
movements of her arms and legs. On examina- warfarin for many years for her history of two
tion, she had nearly constant writhing, non- deep venous thromboses; 10 months before the
rhythmic, dancelike movements of the arms, current presentation, treatment had been switched
legs, and trunk, as well as rolling movements of from warfarin to apixaban. Acetylsalicylic acid
the tongue. She could stand up from a chair had caused hives; there were no other known
while holding onto a walker. Scattered bruises allergies. Before being discharged to the reha-
were present on the lower legs. Imaging studies bilitation facility, the patient had lived alone in a
were obtained. suburban area and had worked in a school. She
CT of the head, performed without the ad- was a lifelong nonsmoker and drank alcohol
ministration of intravenous contrast material, rarely. Her father and brother had diabetes mel-
reportedly showed mild scattered parenchymal litus; there was no family history of abnormal
hypodensities without hemorrhage or evidence movements or stroke.
of an acute infarct. A presumptive diagnosis of The temperature was 36.6°C, the blood pres-
vascular chorea was made, and the patient was sure 125/60 mm Hg, the pulse 79 beats per
treated with oral levetiracetam. On the third minute, the respiratory rate 20 breaths per min-
hospital day, MRI of the head was attempted but ute, and the oxygen saturation 94% while the
was limited by motion artifacts due to involun- patient was breathing ambient air. The body-
tary movements. There were small foci of re- mass index (the weight in kilograms divided by
stricted diffusion in the right frontal and pari- the square of the height in meters) was 23.6. The
etal periventricular white matter within the right patient was sleepy but arousable with verbal
corona radiata and centrum semiovale, findings stimuli. She was oriented to self but not to time
consistent with new small acute-to-subacute in- or place. She could follow simple commands
farcts without hemorrhage or mass effect. with repeated instructions but could not follow
On the fourth hospital day, the dose of leveti- complex commands. She had irregular spontane-
2278 n engl j med 389;24 nejm.org December 14, 2023

Case Records of the Massachuset ts Gener al Hospital
ous movements of the face, mouth, and tongue; Table 1. Laboratory Data.
she also had irregular spontaneous writhing
movements of the arms and legs that were par- Variable Reference Range* On Presentation
tially suppressible. When she was asked to hold Hematocrit (%) 36.0–46.0 26.0
her arms outstretched with the palms facing Hemoglobin (g/dl) 12.0–16.0 7.9
upward while keeping her eyes closed, her right
White-cell count (per μl) 4500–11,000 3950
arm drifted downward, and the palm pronated
Differential count (per μl)
toward the floor. Strength was 4 out of 5 on
right shoulder abduction, elbow flexion, elbow Neutrophils 1800–7700 2620
extension, wrist flexion, and wrist extension; the Lymphocytes 1000–4800 840
remainder of the examination was normal. Monocytes 200–1200 470
Blood levels of electrolytes, alanine amino- Eosinophils 0–900 0
transferase, aspartate aminotransferase, and alka- Basophils 0–300 0
line phosphatase were normal, as were the re-
Bands 0–100 20
sults of kidney-function tests. Urinalysis showed
Platelet count (per μl) 150,000–400,000 225,000
trace ketones and 1+ leukocyte esterase (refer-
ence value, negative); the urine sediment showed International normalized ratio 0.9–1.1 1.4
0 to 2 white cells per high-power field (reference Activated partial-thromboplastin time 22.0–36.0 40.6
value, <10). The erythrocyte sedimentation rate (sec)
was 44 mm per hour (reference range for women Thyrotropin (μIU/ml) 0.40–5.00 5.24
in the patient’s age group, 0 to 40). Additional Free thyroxine (ng/dl)† 0.9–1.8 1.6
laboratory test results are shown in Table 1.
Dr. Hillary R. Kelly: CT of the head performed * Reference values are affected by many variables, including the patient popu
lation and the laboratory methods used. The ranges used at Massachusetts
without the administration of intravenous con- General Hospital are for adults who are not pregnant and do not have medi‑
trast material, as well as CT angiography of the cal conditions that could affect the results. They may therefore not be appro‑
head and neck performed after the administra- priate for all patients.
† To convert the values for free thyroxine to picomoles per liter, multiply by 12.87.
tion of intravenous contrast material, showed no
evidence of an acute territorial infarct and no
change in the long-term findings, including the
previously described areas of encephalomalacia showed no intracranial occlusion, high-grade
and periventricular white-matter hypodensity. stenosis, or aneurysm.
MRI of the head (Fig. 1), performed with and The patient was admitted to this hospital,
without the administration of intravenous con- and diagnostic tests were performed.
trast material, showed multiple foci of restricted
diffusion associated with T2-weighted and FLAIR Differ en t i a l Di agnosis
hyperintensity, findings consistent with acute-
to-early subacute infarcts. Foci were scattered Dr. Bart K. Chwalisz: This 68-year-old woman pre-
throughout the cortex and subcortical white sented with subacute progressive abnormal move-
matter of both cerebral hemispheres. The most ments and confusion. To construct a differential
prominent foci were located along the left tem- diagnosis, I will begin by characterizing the
poro-occipital junction. Numerous foci involved phenomenology and attempting neurologic local-
the cortex of the frontal and parietal lobes along ization.
the precentral and postcentral gyri. There was a The patient had abnormal movements that
small punctate focus of restricted diffusion as- were widely distributed, involving the face,
sociated with T2-weighted and FLAIR hyperin- mouth, tongue, arms, and legs on both sides of
tensity in the right superior cerebellar hemi- her body. The movements were initially intermit-
sphere, a finding consistent with an additional tent but progressively worsened. She had no
small infarct. There was no associated hemor- premonition and considered the movements to
rhage or mass effect. Magnetic resonance angi- be involuntary. The movements affected her abil-
ography of the head, performed without the ad- ity to function and were associated with falls
ministration of intravenous contrast material, despite the use of a walker. Additional neuro-

A B C
D E F
G H

Figure 1 (facing page). MRI of the Head.

Vascular Lesions
An axial fluid-attenuated inversion recovery (FLAIR) Vascular chorea was considered by the treating
image (Panel A), an axial T2-weighted image (Panel B), physicians during the patient’s second hospital
and apparent-diffusion-coefficient and trace diffusion- admission. Large unilateral lesions of the antero-
weighted imaging maps (Panels C and D, respectively) ventral caudate, striatum, or thalamus can cause
show multiple foci of restricted diffusion associated
contralateral chorea or athetosis.1 However, the
with T2-weighted and FLAIR hyperintensity in the pos‑
terior frontal centrum semiovale bilaterally (arrows), infarcts observed on MRI of the head in this pa-
findings consistent with acute-to-early subacute in‑ tient were small and not specifically located in
farcts. Trace diffusion-weighted imaging maps (Panels basal ganglia structures. Small focal lesions rare-
D through H) show additional small foci of restricted ly cause clinically significant movement disorders,
diffusion consistent with acute-to-subacute infarcts
except in the case of unilateral hemiballismus,
throughout the cortex and subcortical white matter of
the frontal and parietal lobes (Panel D, arrowheads). which is caused by damage to the contralateral
Foci are present along the precentral and postcentral subthalamic nucleus. If this patient’s bilateral
gyri (Panels E and F), at the left temporo-occipital junc‑ chorea was a result of vascular lesions, substan-
tion (Panel G), and in the right superior cerebellar tial bilateral infarction of the caudate or similar
hemisphere (Panel H).
structures would probably be present. Overall, I
think vascular chorea is unlikely in this patient.
logic findings included dysarthria, confusion, Genetic Disorders

impaired arousal, and arm weakness. The de- The patient’s presentation in the seventh decade
scription of this patient’s movements is most of life with a subacute course, over a period of
consistent with chorea, which is characterized months, makes a genetic cause of chorea un-
by involuntary, nonrhythmic movements due to likely in this case. Most genetic causes of chorea
continuous flow of muscle contractions from would have an earlier onset or a gradually pro-
one muscle group to another, creating a dance- gressive course, typically over a period of years.
like appearance. Many are autosomal recessive or X-linked disor-
Chorea usually localizes to extrapyramidal ders of childhood. This patient had no clinical
basal ganglia networks.1 Basal ganglionic dis- features supportive of Huntington’s disease, such
eases can be diffuse or discrete. When they are as difficulty with initiating eye movements or a
discrete, they usually also affect adjacent struc- neuropsychiatric prodrome. In addition, she had
tures, such as the internal capsule, hypothala- no other features suggestive of mitochondrial
mus, or cerebral white matter. This patient’s disease, such as hearing loss or short stature.
other neurologic deficits (dysarthria, confusion, Among genetic disorders, acute intermittent
and sleepiness) are nonlocalizing, given that porphyria and other acute hepatic porphyrias
they can all be caused by diffuse or multifocal could be considered because they can cause cen-
cerebral processes or toxic–metabolic abnor- tral nervous system disturbances that rarely in-
malities. Her weakness is not described as being clude movement disorders. However, porphyria
in any particular diagnostic pattern. A pronator commonly also causes peripheral neuropathy,
drift is mentioned, but I interpret this finding which appears to be absent in this patient. It is
with caution because movements resembling important to note that a neurologic presentation
pronation can be seen in patients with chorea. without abdominal pain would be uncommon.
Various neurologic and systemic disorders
have been associated with chorea. The differen- Toxic and Metabolic Disorders
tial diagnosis can be narrowed by considering The patient was not taking any medications as-
the bilateral nature of the abnormal movements, sociated with chorea, such as neuroleptic agents,
the time course of the illness, the patient’s anticonvulsant agents, amphetamines, or anti-
medical history and medications, and the find- parkinsonian medications. There was no history
ings on laboratory testing and MRI of the head of an anoxic insult, carbon monoxide poisoning,
performed at the time of admission. or an occupational exposure (e.g., exposure to

heavy metals). Hyperglycemia can cause chorea, thy. Small-cell carcinoma of the lung is the most
as can hypernatremia and hyponatremia, but common associated cancer. Paraneoplastic cho-
these findings were not present in this patient. rea may be associated with positivity for neural
Hyperthyroidism can cause movement disorders, antibodies,7 which is best detected with antibody
most commonly an enhanced physiologic tremor panel testing. However, some of these antibod-
but rarely also chorea.2,3 However, this patient’s ies may also be present in patients with non-
blood thyrotropin level was only mildly elevated, paraneoplastic autoimmune chorea.
and the blood free thyroxine level was normal.
Hepatocerebral degeneration can occur in Autoimmune Disorders
patients with any acquired liver disease or with After levodopa-induced dyskinesias and Hun-
portosystemic shunts, and it can result in pro- tington’s chorea, autoimmune chorea is the most
gressive tremor and other movement disorders, common type of chorea in adults. It may be as-
such a myoclonus, dystonia, or chorea.4 MRI of sociated with systemic autoimmune conditions,
the head may show signal hyperintensity in the such as systemic lupus erythematosus (SLE) and
basal ganglia on T1-weighted imaging, which is antiphospholipid syndrome (APS).
due to manganese deposition. This patient had Chorea is the most common movement disor-
normal results of liver-function tests, had no der among patients with SLE, occurring in 2% of
examination findings compatible with liver dis- patients.8 When chorea occurs in patients with
ease, and had no imaging findings suggestive of SLE, it is bilateral in 55% of cases and is limited
hepatocerebral degeneration. to a single episode in 66% of cases, although
multiple episodes are possible. Other neuropsy-
Infections chiatric symptoms of SLE can include seizures,
Infection with group A beta-hemolytic strepto- delirium, brain ischemia, and psychiatric distur-
coccus (acute rheumatic fever) can cause Syden- bances, ranging from personality changes to
ham chorea, but this type of chorea is primarily psychosis. This patient had no musculoskeletal,
a childhood disease with a decreasing incidence mucocutaneous, serosal, or renal features of SLE,
in the United States. In addition, there is no re- but she did have anemia and leukopenia.9
port of pharyngitis or other features of acute APS can occur as a primary disorder or can
rheumatic fever in this patient. She is at low be secondary to connective-tissue disorders, in-
epidemiologic risk for human immunodefi- cluding SLE. It is characterized by vascular
ciency virus encephalitis and tuberculosis, two thrombosis (venous, arterial, or small-vessel
other infections associated with chorea. Sporadic thrombosis) and complications during preg-
Creutzfeldt–Jakob disease, which is the most nancy. A wide variety of neurologic manifesta-
common human prion disease, has a heteroge- tions have been reported with APS, such as
neous spectrum of clinical manifestations that ischemic stroke, migraine, myelopathy, epilepsy,
can include dementia, behavioral changes, vision and dementia. Chorea is the most common
deficits, ataxia, and movement disorders.5 MRI movement disorder among patients with APS,
of the head typically shows restricted diffusion occurring in 1.3% of patients.10 The pathogene-
in neocortical or subcortical regions,6 which was sis may extend beyond ischemia, given that
not present in this patient. antiphospholipid antibodies have been shown to
bind to neuronal structures and possibly change
Inflammatory Disorders behavior in mice.8,10
Inflammatory disorders that can cause chorea
include multiple sclerosis, neurosarcoidosis, and Multifocal Strokes
neuro-Behçet’s disease. These disorders can be Is there a unifying diagnosis in this case that
ruled out because the characteristic imaging explains the chorea and the presence of multifo-
findings were not present on MRI of the head. cal small infarcts despite anticoagulation with
apixaban? The differential diagnosis for strokes
Paraneoplastic Disorders despite anticoagulation includes reduced efficacy
Paraneoplastic chorea is most likely to occur in of the anticoagulant in the individual patient,
older men with coexisting peripheral neuropa- poor adherence to the anticoagulant regimen,

and the presence of stroke mechanisms that are antibodies were met. The anticardiolipin IgG
less amenable to anticoagulation, such as hyper- and IgM persisted after 12 weeks, meeting the
tensive or diabetic small-vessel occlusion, vascu- criteria for APS.11
litis, or infective endocarditis. When a patient The presence of antinuclear antibodies at a
has APS or a cancer-associated hypercoagulable titer of 1:160 in a homogeneous and speckled
state, different anticoagulants may have differ- pattern (dual pattern) on an indirect immuno-
ent effects. Indeed, this patient’s treatment had fluorescence assay with human epithelial cells,
been switched from warfarin to apixaban 10 as well as the presence of anti–double-stranded
months before the current presentation, and DNA antibodies at a high titer (1:320) on a Cri-
apixaban may be a less effective anticoagulant thidia luciliae immunofluorescence assay, estab-
in patients with APS. The presence of arterial lished the serologic diagnosis of SLE in this
strokes despite anticoagulation, along with the patient.12 The low C3 level (56 mg per deciliter;
history of venous thromboembolism, is very sug- reference range, 81 to 157) and low C4 level (6 mg
gestive of a diagnosis of APS possibly due to per deciliter; reference range, 12 to 39) sug-
underlying SLE. To establish this diagnosis, I gested that classical pathway activation by im-
would perform testing for lupus anticoagulant mune complexes had led to inflammation and
and for anticardiolipin and anti–β2-glycoprotein tissue injury of multiple organs. These immune
I antibodies, as well as antinuclear antibody test- complexes activate platelets, endothelial cells,
ing to determine whether the patient has SLE. and the coagulation cascade.13
Dr . B a r t K . Ch wa l isz’s Di agnosis L a bor at or y Di agnosis

Antiphospholipid syndrome possibly due to sys- Antiphospholipid syndrome due to systemic lu-
temic lupus erythematosus. pus erythematosus with associated hypocomple-
mentemia and tissue injury.
Di agnos t ic Te s t ing
Discussion of M a nagemen t
Dr. Mandakolathur R. Murali: The prolonged acti-
vated partial-thromboplastin time (aPTT) and Dr. Alice W. Flaherty: This patient’s history illus-
international normalized ratio in this patient trates an important fact about severe chorea: it
could be attributed to the use of apixaban. How- is often undertreated. Over a period of 2 months,
ever, the prolonged aPTT could also be due to a her chorea worsened until she could no longer
coagulation factor deficiency or the presence of work, live independently, or ambulate without a
a lupus anticoagulant. A 1:1 mixing study (in walker, and she had dangerous falls. Yet, despite
which a plasma specimen from the patient was assessments by seven different neurologists,
mixed with normal plasma in equal proportions) she never received any standard chorea treat-
revealed no deficiency of clotting factors and no ment. Why?
inhibitors of intrinsic or contact factors that af- One common reason that treatment is with-
fect the aPTT. Therefore, lupus anticoagulant held from patients with idiopathic or crypto-
testing was performed. The lupus anticoagulant– genic chorea is the neurologist’s hesitation to
sensitive aPTT test was positive, and therefore, treat symptoms without a known cause. Yet,
the three confirmative tests for antiphospholipid treatment of chorea is compatible with ongoing
antibodies were performed. The hexagonal diagnostic workup.
phase phospholipid neutralization test was posi- A second reason that treatment can be with-
tive, confirming the presence of a lupus antico- held is barriers to, and side effects of, the use of
agulant. The test for anticardiolipin IgG and vesicular monoamine transporter 2 (VMAT2)
IgM was strongly positive (114.7 units and 26.0 inhibitors — a class of drugs that are sometimes
units, respectively; reference range, 0.0 to 15.0). used to treat idiopathic chorea because they have
The test for anti–β2-glycoprotein I antibodies been approved by the Food and Drug Adminis-
was negative. Therefore, two of the three criteria tration for the treatment of Huntington’s chorea
for confirming the presence of antiphospholipid and tardive dyskinesia (a drug-induced movement

disorder). Few doctors feel comfortable prescrib- antiphospholipid antibodies, the majority of pa-
ing VMAT2 inhibitors. These medications are tients did not have findings that correlated to
associated with clinically significant sedation, ischemic stroke on MRI of the head,10 which was
and treatment needs to be started slowly; the also the case in this patient. Nonetheless, she
tendency to cause parkinsonism and depression had a strong indication for lifelong anticoagula-
often limits the dose. Prior-authorization re- tion with warfarin, on the basis of her clinical
quirements from insurance companies create diagnosis of APS, her history of two deep venous
paperwork barriers and often stipulate initial thromboses, and her high-risk antiphospholipid
treatment with traditional chorea drugs, namely antibody profile (with positive testing for an-
first-generation dopamine D2 receptor antago- tiphospholipid antibodies, including a high titer
nists, such as haloperidol. of anticardiolipin IgG),15 in addition to the cho-
Many doctors are so uncomfortable prescrib- rea and subacute strokes. Therefore, her treat-
ing first-generation dopamine D2 receptor antago- ment was switched from apixaban to warfarin.
nists that they either prescribe nothing or, in an A second proposed mechanism is an immune-
attempt to avoid tardive dyskinesia, prescribe mediated process of neuronal injury. However,
second-generation agents with weak dopamine on the basis of limited evidence from small,
D2 receptor blockade, such as quetiapine. How- observational studies, immunosuppression is
ever, dopamine D2 receptor blockade is needed not warranted in all cases of chorea due to
to treat chorea, and there are no reported cases APS and SLE and can be reserved for severe or
of tardive dyskinesia occurring in patients who refractory cases.14 Because this patient had an
already had chorea. excellent clinical response to treatment with
In this patient, while we awaited the results haloperidol, immunosuppression was not ini-
of diagnostic testing for the cause of chorea, we tiated.
elected to start treatment with haloperidol be- The administration of hydroxychloroquine
cause it was immediately available, is a much was initiated for the treatment of SLE, but the
less potent sedative than VMAT2 inhibitors, and patient did not have additional disease manifes-
is a mood stabilizer, whereas VMAT2 inhibitors tations to warrant immunosuppression. She will
are sometimes depressants. Within 1 day after have close follow-up with rheumatology special-
the patient began treatment with haloperidol, ists to monitor for the development of other
her chorea dramatically decreased. manifestations of SLE.
Dr. April M. Jorge: A key aspect of the treatment Dr. Flaherty: The patient was discharged from
of chorea resulting from APS and underlying the hospital to a rehabilitation facility with
SLE includes therapy with dopamine D2 receptor minimal chorea while she was receiving halo-
antagonists to alleviate symptoms.14 Treatment peridol. The use of haloperidol caused some
with haloperidol had already been started in this restless leg symptoms at bedtime, which re-
patient when the test results that confirmed the solved with the use of gabapentin. The courses
diagnoses of APS and SLE became available. On of haloperidol and gabapentin were eventually
the basis of the proposed pathologic mecha- tapered off, and the patient was able to return to
nisms of chorea due to APS and neuropsychiatric independent living.
SLE, anticoagulation and immunosuppression
were additional treatment considerations in this Fina l Di agnosis
patient.
One proposed mechanism is an ischemic Chorea due to antiphospholipid syndrome and
process due to microvascular or macrovascular underlying systemic lupus erythematosus.
thrombosis mediated by antiphospholipid anti- This case was presented at the Medicine Case Conference.
bodies leading to reduced circulation to the Disclosure forms provided by the authors are available with
the full text of this article at NEJM.org.
basal ganglia in patients with APS. However, in We thank Drs. Sebastian Unizony and Marcello Matiello for
multiple case series of chorea associated with their assistance with preparation of the case presentation.

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The n e w e ng l a n d j o u r na l of m e dic i n e

Case Records of the Massachusetts General Hospital

Founded by Richard C. Cabot

Case 38-2023: A 68-Year-Old Woman

Pr e sen tat ion of C a se

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The New England Journal of Medicine

Figure 1 (facing page). MRI of the Head.

logic findings included dysarthria, confusion, Genetic Disorders

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Dr . B a r t K . Ch wa l isz’s Di agnosis L a bor at or y Di agnosis

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