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Ballistic-Choreic Movements as the Presenting Feature of Renal Cancer
Kathy A. Kujawa, MD, PhD;
Vanda R. Niemi, MD;
Marie A. Tomasi, MD;
Norman W. Mayer, MD;
Elizabeth Cochran, MD;
Christopher G. Goetz, MD
Arch Neurol. 2001;58:1133-1135.
ABSTRACT
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Background The paraneoplastic syndromes can involve multiple areas of the central
nervous system and result in a variety of neurological symptoms. To our knowledge,
severe, rapidly progressive, and drug-resistant ballistic-choreic movements
have not been previously described as the presenting feature of renal cell
carcinoma.
Patient and Methods A previously healthy 55-year-old man developed limb ballismus and involuntary
choreic movements of his face over several weeks. Extensive laboratory, diagnostic,
and radiographic studies failed to reveal a cause, until an abnormality on
a chest x-ray film prompted a search for a primary neoplasm and a final diagnosis
of renal cell carcinoma. High doses of medications traditionally used to treat
choreic disorders had no effect on the abnormal movements. A biopsy specimen
of the basal ganglia showed focal encephalitic changes but no malignant neoplasm.
Conclusions Whereas prior cases of paraneoplastic syndromes with chorea have been
reported in other forms of cancer, our case was significant because, to our
knowledge, renal cell carcinoma has not been previously reported in association
with this syndrome. Furthermore, the chorea was categorically resistant to
pharmacological treatment, and the movement disorder was the initial and only
focal neurological feature of the primary illness.
INTRODUCTION
THE DIFFERENTIAL diagnosis of chorea, which is extensive, includes hereditary
(Huntington disease and Wilson disease), infectious (Sydenham chorea), metabolic
(abnormal sodium, glucose, and magnesium levels), endocrine (hyperthyroidism),
inflammatory (vasculitis, lupus, and sarcoidosis), cerebrovascular (arteriovenous
malformations, stroke, and polycythemia), levodopa intoxication, and neurodegenerative
disorders (Hallervorden-Spatz disease).1, 2
Although neuroleptic and anticonvulsant medications are used in the treatment
of chorea, these drugs can also induce chorea. Rarely, chorea can occur as
a form of paraneoplastic central nervous system disease. We describe a patient
who presented with severe, disabling, and drug-resistant ballistic-choreic
movements that represented the first and isolated focal neurological symptom
of renal cell carcinoma.
REPORT OF A CASE
A 55-year-old white man was referred for evaluation and treatment of
ballistic and choreiform movements. He was in his usual state of health until
6 weeks before admission, when he first noted shortness of breath, insomnia,
and anxiety. The results of routine blood tests, chest radiography, transthoracic
echocardiography, and an exercise stress test were normal. Over the next week,
the patient developed mild involuntary movements of his face and limbs, and
his family noted slurred but appropriate speech. He then rapidly developed
more severe involuntary movements, difficulties with his balance, lightheadedness,
and a mild frontal headache. He was first admitted to a community hospital
but was transferred to our university hospital for further evaluation approximately
3 weeks after the initial onset of involuntary movements.
The patient's medical history was significant for a traumatic amputation
of the right middle finger and pneumonia. He was not taking any prescription
medications. He was married and had an adult son and a developmentally delayed
daughter. He was employed full-time as a truck driver transporting organic
solvents but had no history of accidental exposure. The patient had stopped
smoking 20 years ago, drank alcohol on social occasions, and denied the use
of illicit substances. His parents were alive and well, and there was no family
history of neurological illness or movement disorder.
On general examination, the patient was a moderately obese man in no
apparent distress. His vital signs, including temperature, respiration rate,
blood pressure, and pulse rate, were normal. His cardiac, lung, and abdominal
examinations revealed no abnormalities. A nonpalpable petechial rash was noted
over his neck, shoulders, and back. His neurological examination revealed
moderately severe involuntary movements of his extremities, which were more
pronounced in his arms, neck, and face. These movements were random and unpredictable
at rest and had a choreic and ballistic quality that increased when the patient
was stimulated or speaking. He was alert and able to follow commands but was
not oriented to time and place. His speech was appropriate but markedly dysarthric,
with intact naming and repetition. The results of his cranial nerve and muscle
strength testing were normal. Pin sensation was symmetrically diminished distally
to his elbows and ankles. He was areflexic, with bilateral Babinski responses.
He could sit upright, but gait testing could not be completed owing to the
severity of the involuntary movements. Finger-to-nose and heel-to-shin testing
evoked ballistic movements of the active extremity.
The results of the following laboratory investigations were normal or
negative: glucose, electrolytes, complete blood cell count, urinalysis, coagulation
studies, erythrocyte sedimentation rate, porphyrins, toxicology screen, genetic
testing for Huntington disease, ceruloplasmin, heavy metals, thyroid function,
rheumatoid factor, rapid plasma reagin test, human immunodeficiency virus,
serum protein electrophoresis, and Lyme, thyroid, antiphospholipid, and anti-Hu
antibodies. The following values were abnormal: ammonia, 38 mg/dL (27 µmol/L)
(reference range, 11-35 mg/dL [8-25 µmol/L]); antistreptolysin antibody,
599 IU/mL (reference range, 0-200 IU/mL); and C-reactive protein, 41 µg/mL
(reference range, 0-5 µg/mL). A chest x-ray film showed mild pulmonary
edema with upper lobe pulmonary vessel distention. A lumbar puncture completed
with the patient under general anesthesia revealed the following values: leukocyte
count, 176/µL (lymphocytes, 62%; neutrophils, 9%); erythrocyte count,
175 000/µL; protein, 2.1 g/dL; and glucose, 112 mg/dL (6.2 mmol/L).
Bacterial, fungal, and acid-fast bacilli cultures were negative. The findings
of magnetic resonance imaging of the brain, with and without contrast, were
unremarkable. A transesophageal echocardiogram showed normal ventricular size
and function, with normal valvular morphological features. There was no evidence
of vasculitis on a 4-vessel cerebral angiogram. The results of nerve conduction
studies were normal. A biopsy specimen of the patient's skin lesions revealed
nonspecific dermatitis. Review of a right basal ganglia stereotactic biopsy
specimen showed perivascular and transmural inflammatory infiltrates, without
destruction of vessel walls or necrotic debris (Figure 1). As these findings were suggestive but not definitive
of primary vasculitis, high-dose intravenous methylprednisolone sodium succinate
therapy was initiated. The results of special stains later showed parenchymal
infiltration by both T lymphocytes and microglia. These findings, along with
the vascular changes, suggested encephalitis rather than vasculitis, and the
methylprednisolone therapy was discontinued after 4 days.
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Biopsy specimen of the basal ganglia demonstrates 2 vessels with
abundant perivascular and transmural lymphocytes and surrounding reactive
astrocytes (hematoxylin-eosin, original magnification x200).
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During the hospitalization, the patient's involuntary movements persisted
despite increased doses of haloperidol (60 mg/d), clonazepam (3 mg/d), and
valproic acid (1800 mg/d). Tetrabenazine therapy was started, and the dosage
was titrated up to 200 mg/d without significant improvement of the ballistic-choreic
movements. The patient's cognition deteriorated over several days, and he
was no longer oriented to time and place. Because of increasing agitation,
he required sedation with lorazepam. A low-grade fever prompted additional
chest radiography, and the radiogram showed new infiltrative changes in the
right hilar region. A computed tomographic scan of the chest, abdomen, and
pelvis demonstrated masses in both kidneys and the omentum, right adrenal
gland, mediastinal lymph nodes, and lungs. Findings of a computed tomography-guided
biopsy of the omental mass confirmed the suspected diagnosis of metastatic
renal cell carcinoma. The patient's cognition continued to deteriorate without
new focal neurological symptoms, and his family elected not to resuscitate
him in the occurrence of a cardiovascular event. He received a single dose
of chemotherapy (vinblastine sulfate and interferon), later developed respiratory
failure, and died 3 weeks after diagnosis and approximately 10 weeks after
the onset of the involuntary movements. At autopsy, additional metastases
were found in the left adrenal gland and pancreas. Cardiomegaly, pulmonary
edema, and congestive hepatosplenomegaly were present. A section of the putamen
showed numerous vessels with chronic inflammation, parenchymal astrocytosis,
and slight microglial proliferation, but no neoplastic cells.
COMMENT
The paraneoplastic syndromes are remote, nonmetastatic manifestations
of cancer that can affect multiple areas of the nervous system. These syndromes
can have several presentations, including encephalitis, cerebellar degeneration,
motor neuron disease, impaired neuromuscular transmission, and motor, sensory,
and autonomic neuropathy.3 Movement disorders
have also been reported as a remote complication of malignancy. The first
reported case of chorea presenting as a paraneoplastic syndrome involved a
45-year-old woman with a sensory neuropathy, nystagmus, and ataxia who subsequently
developed choreic movements of the extremities over a 2-month period.4 Her movements evolved from choreoathetoid to dystonic
over the course of her hospitalization. A computed tomographic scan of her
chest revealed a left hilar mass that was diagnosed as oat cell carcinoma
at autopsy approximately 4 months after initial presentation. Batchelor et
al5 later described a 67-year-old woman with
dysarthria and ataxia who developed progressive choreic movements of her face,
neck, and extremities 13 months after the onset of neurological symptoms.
Hodgkin disease was confirmed after a biopsy specimen of a splenic lymph node
was obtained 2 months later, and the patient died approximately 17 months
after the initial onset of symptoms. Cases of chorea developing months after
the diagnosis of lung,6 colon, and ovarian
tube cancer have been described.7 Chorea was
also reported as the initial presentation of acute lymphoblastic leukemia
in a child who had resolution of movements after the cancer was in remission.8
The inability to pharmacologically control our patient's involuntary
movements suggested the possibility of a paraneoplastic syndrome, since previously
cited cases have shown only partial or transient improvement with medication.5, 6, 7 His course was rapidly
progressive, with severe chorea that was resistant to multiple medications,
including a neuroleptic, a benzodiazepine, an anticonvulsant, an intravenous
corticosteroid, and a dopamine-depleting agent.
Our case was significant for chorea as the initial and only focal neurological
feature of renal cell carcinoma. The search for a primary neoplasm was conducted
because of the medication-resistant chorea and because an abnormality was
detected on a chest x-ray film. While not specific, the inflammatory findings
in the basal ganglia biopsy specimen were typical of paraneoplastic encephalitis.9 Several studies, which suggested only mild pulmonary
edema, had been completed over the course of the patient's protracted hospitalization.
Although Chamouard et al10 published a case
of chorea as a complication of polycythemia in a patient with renal adenocarcinoma,
we believe that the case reported herein is the first case of chorea that
preceded the diagnosis of renal cell carcinoma. While the list of possible
causes of chorea is extensive, a paraneoplastic syndrome should be considered
in the differential diagnosis of a patient who presents with this isolated
movement disorder.
AUTHOR INFORMATION
Accepted for publication January 24, 2001.
From the Departments of Neurological Sciences (Drs Kujawa, Niemi, Tomasi,
Cochran, and Goetz) and Pathology (Dr Cochran) and Rush Medical College (Dr
Mayer), Rush-Presbyterian-St Luke's Medical Center, Chicago, Ill. Dr Kujawa
is now with the Department of Neurology, Glenbrook Hospital, Glenview, Ill;
Dr Niemi is now with Noran Neurological Clinic, Minneapolis, Minn; and Dr
Mayer is now with the Department of Neurological Surgery, University of Louisville,
Louisville, Ky.
Corresponding author and reprints: Kathy A. Kujawa, MD, PhD, Department
of Neurology, Glenbrook Hospital, 2100 Pfingsten Rd, Glenview, IL 60025 (e-mail: k-kujawa{at}northwestern.edu).
REFERENCES
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1. Feigin A, Kieburtz K, Shoulson I. Treatment of Huntington's disease and other choreic disorders. In: Kurlan R, ed. Treatment of Movement Disorders. Philadelphia, Pa: JB Lippincott; 1995:337-364.
2. Fortin PR. Vasculitides associated with malignancy. Curr Opin Rheumatol. 1996;8:30-33.
PUBMED
3. Patchell RA, Posner JB. Neurologic complications of systemic cancer. Neurol Clin. 1985;3:729-750.
PUBMED
4. Albin RL, Bromberg MB, Penney JB, Knapp R. Chorea and dystonia: a remote effect of carcinoma. Mov Disord. 1988;3:162-169.
FULL TEXT
| PUBMED
5. Batchelor TT, Platten M, Palmer-Toy DE, et al. Chorea as a paraneoplastic complication of Hodgkin's disease. J Neurooncol. 1998;36:185-190.
FULL TEXT
| PUBMED
6. Heckmann JG, Lang CJ, Druschky A, Claus D, Bartels O, Neundorfer B. Chorea resulting from paraneoplastic encephalitis. Mov Disord. 1997;12:464-466.
FULL TEXT
| PUBMED
7. Ros T, Pirtosek Z, Flisar D. Progressive encephalomyelitis with rigidity and chorea: three cases
with extrapyramidal paraneoplastic disorders [abstract]? Mov Disord. 1998;13(suppl 2):159.
8. Schiff D, Ortega JA. Chorea, eosinophilia, and lupus anticoagulant associated with acute
lymphoblastic leukemia. Pediatr Neurol. 1992;8:466-468.
PUBMED
9. Scaravilli F, An SF, Groves M, Thom M. The neuropathology of paraneoplastic syndromes. Brain Pathol. 1999;9:251-260.
PUBMED
10. Chamouard JM, Smagghe A, Malalanirina BH, Davous P, Poisson M. Choree revelatrice d'une ployglobulie et d'un adenocarcinome renal. Rev Neurol. 1992;148:380-382.
PUBMED
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