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Clinical Characteristics and Long-Term Outcomes of Movement Disorders in Childhood Thalamic Tumors
Accepted Manuscript Clinical Characteristics and Long-term Outcomes of Movement Disorders in Childhood Thalamic Tumors Zsila S. Sadighi, MD, Jennifer Zabrowski, RN, Frederick A. Boop, MD, Alberto Broniscer, MD, Amar Gajjar, MD, Raja B. Khan, MD PII:
S0887-8994(16)30242-9
DOI:
10.1016/j.pediatrneurol.2016.08.012
Reference:
PNU 8969
To appear in:
Pediatric Neurology
Received Date: 12 April 2016 Revised Date:
11 August 2016
Accepted Date: 14 August 2016
Please cite this article as: Sadighi ZS, Zabrowski J, Boop FA, Broniscer A, Gajjar A, Khan RB, Clinical Characteristics and Long-term Outcomes of Movement Disorders in Childhood Thalamic Tumors, Pediatric Neurology (2016), doi: 10.1016/j.pediatrneurol.2016.08.012. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Clinical Characteristics and Long-term Outcomes of Movement Disorders in
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Childhood Thalamic Tumors
Zsila S. Sadighi MDa, Jennifer Zabrowski, RNa, Frederick A. Boop, MDb, Alberto Broniscer, MDc, Amar Gajjar, MDa,c, Raja B. Khan, MDa
Department of Pediatric Medicine, Division of Neurology, St. Jude Children’s Research
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a
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Hospital, Memphis, TN 38105, USA (email: ZS, [email protected]; JZ, [email protected]; RK, [email protected]) b
Department of Neurosurgery, University of Tennessee Health Science Center, Memphis, TN,
USA; Le Bonheur Neuroscience Institute, Le Bonheur Children's Hospital, Memphis, TN, USA; Semmes-Murphey Neurologic and Spine Institute, Memphis, TN, USA; Division of
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Neurosurgery, St Jude Children's Research Hospital, Memphis, TN 38105, USA (email: [email protected]) c
Department of Oncology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
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(email: AB, [email protected]; AG, [email protected])
Corresponding Author
Zsila S. Sadighi, MD, Division of Neurology, MS 135, 262 Danny Thomas Place, Memphis, TN 38105; Tel.: 901-595-8574; fax: 901-595-8548; e-mail: [email protected] Running Title: Movement Disorder in Thalamic Tumor Manuscript word count: 2,112
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Abstract
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Background: We studied the outcomes of movement disorders that were associated with childhood thalamic tumors.
Methods: We retrospectively reviewed 83 cases of childhood thalamic tumors treated at our
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institution from 1996 to 2013 to document the incidence and outcome of movement disorders. Magnetic resonance imaging was used to analyze the involvement of thalamic nuclei, and three
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instruments were used to rate the severity of the disorders.
Results: Nine (11%) patients had one or more of the following movement disorders: postural tremor, resting tremor, ballism, dystonia, myoclonus, and athetosis. Median age at tumor diagnosis was 7 years (range, 0.25-11 years), and that at movement disorder onset was 8 years
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(range, 1.5-11 years). Movement disorders developed at a median of 1.5 months (range, 0-4 months) after surgical resection. The severity of the disorders was either unchanged or slightly improved during follow-up. The red nuclei were the only thalamic structures that showed tumor
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involvement in all nine patients.
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Conclusions: No specific injury of the thalamic nuclei was associated with movement disorders in children with thalamic tumors, and the severity of those disorders did not change over time. Keywords: Thalamic tumors, childhood, movement disorder, outcome
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Introduction Thalamic tumors are uncommon in children and may comprise 0.84% to 5.2% of all intracranial childhood tumors.1 This discrepancy is due to difficulty in distinguishing between primary
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thalamic tumors (i.e., those that originate from the thalamus) and secondary thalamic tumors that arise from adjacent structures (i.e., caudate nuclei, brain stem, or pineal gland). These neoplasms are usually low-grade gliomas, but they can have histologic properties of grade III and IV
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astrocytoma. However, other tumor pathologies also have been reported.1, 2 Confirmation of diagnosis requires tumor biopsy and/or resection.3 Puget et al. found that patients with low-grade
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thalamic tumors experience better survival when more than 90% of the tumor is resected and the duration of symptoms is longer than 2 months.4 Bernstein et al. found that patients with thalamic malignancy survived approximately 1 year, regardless of the extent of resection.3 Bilateral thalamic tumors are even rarer and may have a worse prognosis.5 The clinical signs and
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symptoms of thalamic tumors can be burdensome and include sensory syndrome, motor disorders, oculomotor deficits, increased intracranial pressure, seizures, and movement disorders. Movement disorders occur infrequently in patients with thalamic tumors; their prevalence ranges
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from 1% to 33% in pediatric and adult studies.2, 3, 6, 7 Also, the data on the severity and outcome
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of movement disorders in these patients are inadequate. The symptoms of movement disorders are typically associated with large thalamic low-grade astrocytomas and most likely result from surgical injury or the tumor compressing the neurons or neuronal pathways in the thalamic relay center.8-11 Movement disorders reported in thalamic tumors include tremor, dystonia, chorea, ballism, and myoclonus.9 To our knowledge, no one has systematically correlated the anatomical locations of thalamic tumors or surgical lesions with the development of movement disorders and their outcomes. Therefore, we studied movement disorders in children with thalamic tumors 3
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and attempted to identify specific injuries to the thalamic nuclei that were associated with those disorders.
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Methods This retrospective review was approved by the St. Jude Institutional Review Board. Our query of the hospital’s neuro-oncology database for thalamic tumors identified 83 patients who were 18
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years or younger at diagnosis and treated at our institution from 1996 through 2013.
All 83 medical records were first reviewed by a study nurse to identify patients who may have
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had a movement disorder. Those charts were then reviewed by a study neurologist (RBK) blinded to the Magnetic resonance imaging (MRI) data to determine whether a movement disorder was present, and if so, its severity, response to therapy, and long-term outcome. MRI scans of all patients were reviewed by the other study neurologist (ZSS) blinded to the clinical
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data to define the surgical injury to thalamic nuclei and involvement with tumor. The anatomical locations of lesions seen on MRIs were assessed using a neuro-anatomy atlas with corresponding coronal, sagittal, and axial slices to identify nuclei-specific injuries.12 All tumors were
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histologically confirmed after stereotactic biopsy, subtotal resection, or gross total resection. Tumors were graded according to the classification system of the World Health Organization.13
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Assessment of Movement Disorders
The severity of movement disorders was determined using clinical information obtained by chart review and retrospectively applying the Karnofsky Performance Scale (KPS),14 Extrapyramidal Symptom Rating Scale (ESRS),15 and Clinical Global Impression of Severity (CGI-S)16 at the first and last follow-up visits. Our institution has had a systematic neurologic evaluation scale in place since 2001. All of the patients included in this study were seen by a neurologist, and most
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of them had findings recorded on paper or electronic chart based on the scale. All patients had at least one examination available in their charts. The KPS scale, which ranges from 0 (dead) to 100 (no evidence of motor weakness or impaired function), indicates the patient’s functional
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status. ESRS, which ranges from 0 (absent) to 6 (extremely severe), includes subscales for
assessing tremor (8 body parts summed to a maximum score of 48), dyskinesia (10 body parts summed to a maximum score of 60), and dystonia (7 items summed to a maximum score of
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42).15 CGI-S scores range from 0 (absent) to 8 (extremely severe), which assess overall severity
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of tremor, dyskinesia, and dystonia in disease.16
We defined tremor as rhythmic uncontrollable shaking of a body part. Postural tremor appeared when the patient was directed to sustain a posture, such as stretching one’s arms out. Dystonia was defined as a sustained contraction of a single or group of muscles. Myoclonus was defined as a sudden, single involuntary muscle jerk. Chorea was irregular, jerky spontaneous movements
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predominantly in proximal limb muscles, and athetosis was slower writhing movements predominantly in distal limb muscles. Finally, ballism was more explosive, jerky, and higher
Results
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amplitude flinging of a proximal limb(s).
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Clinical Characteristics
After chart review of 83 patients with thalamic tumors, we identified nine (11%) who experienced at least one type of movement disorder during the course of their illness. Median age at tumor diagnosis was 7 years (range, 0.25-11 years), and median age at movement disorder onset was 8 years (range, 1.5-11 years). Median time to first neurologic evaluation was 4 months (range, 1-36 months) after movement disorder onset, and median time to last follow-up was 3
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years (range, 0.2-11 years) after movement disorder onset. None of the patients had a family history of movement disorder, as determined by their answer to a question about whether any family member had ever been diagnosed with abnormal body movements or gait. All patients
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also had a normal early development.
Movement disorders included postural tremor (n=7), resting tremor (n=2), ballism (n=4),
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dystonia (n=2), myoclonus (n=2), athetosis (n=4): five patients had more than one type of
movement disorder present concurrently. Both low- and high-grade tumors were present in
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patients with movement disorders (Table 1). Movement disorder developed in eight patients at a median of 1.5 months (0-4 months) after surgery; one patient had movement disorder onset 11 months before surgery. The extent of tumor resection ranged from stereotactic biopsy (n=5), to subtotal resection (n=3), to complete tumor resection (n=1). Conformal radiation therapy (5459.4 Gy) was used as an adjuvant treatment in eight patients at a median time of 2.5 years (range,
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0.83-5 years) after tumor diagnosis. Six of the eight patients received adjuvant chemotherapy as well. Four patients required a second surgery at a median time of 4 years (range, 1-12 years) after the first; this procedure did not influence the intensity or morphology of the movement
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disorder in any patient (Table 1). Two patients had bithalamic tumors, and seven had unilateral
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tumors. In the latter group, the movement disorder was contralateral to the tumor site. Six patients had tumors confined to the thalamus, whereas three had tumor extension into surrounding structures (i.e., corpus callosum, lateral ventricle, basal ganglia, internal capsule, and midbrain) (Tables 1-2).
The postoperative MRIs showed surgical lesions in the pulvinar (n=4), mediodorsal (n=2), ventrolateral (n=2), centromedian (n=1), anterior (n=1), and laterodorsal (n=1) regions of the thalamus and in the substantia nigra (n=1), and red nucleus (n=1) (Figure 1). Of the seven 6
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unilateral thalamic tumors, four invaded the entire thalamus, and three invaded all but the anterior region. All nine patients had tumors involving the red nucleus, and six had tumors involving the substantia nigra (Table 2). Post-operative intra tumoral hemorrhage developed in
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one patient 3 weeks after the biopsy. Movement disorder appeared a week after the hemorrhage in this patient.
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Movement Disorder Severity and Outcomes
Postural tremor was unilateral and in one extremity in six patients; it was bilateral in one patient
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and involved both the upper and lower extremities. Both athetosis and ballism involved one extremity in two patients and involved ipsilateral upper and lower extremities in four patients. Myoclonus was present in one upper limb in one patient and in one upper and one lower extremity in the other. Resting tremor was unilateral in one patient and bilateral in the other. The two patients with bilateral thalamic tumors and involvement of the red nucleus and substantia
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nigra had unilateral postural tremor only.
The KPS score remained relatively stable over time in patients with movement disorder. The
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median KPS score was 80 (range, 60-90) at initial visit and was unchanged at 80 (range, 50-90) at the last follow-up. Tremor severity did not change over time, as measured by ESRS and CGI-S
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(Table 2). We saw some improvement of dystonia with ESRS but not with CGI-S. Athetosis and ballism, both defined as dyskinesia, improved over time, as measured by ESRS and CGI-S. All ESRS improvements were modest and most likely not clinically significant as CGI-S scores did not improve meaningfully (Table 2). We did not recognize any pattern of tumor involvement of thalamic nuclei by surgical injury. By last follow-up, symptoms showed no change over time in three patients: one patient had postural
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tremor and dystonia; one had postural tremor, athetosis, and myoclonus; and one had athetosis. One patient experienced worsening of postural tremor, and another had complete resolution of ballism. Finally, four patients showed improvement in their movement disorder: one patient had
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resting tremor and postural tremor, athetosis, and ballism; one had postural tremor and ballism; one had athetosis, ballism, dystonia, and postural tremor; and one had resting tremor and postural
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tremor.
Eight of nine patients received various pharmacological interventions [e.g., steroids, gamma-
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amino butyric acid (GABA) A and B agonists, anti-seizure medications, alpha-2 agonists, anticholinergics, dopa agonists, calcium channel blockers, and botulinum toxin injections], and four received multiple medications. Although such treatments resulted in some initial benefit, improvement was not clinically meaningful. Therefore, patients elected to discontinue the
Discussion
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treatment.
This retrospective review is unique in that it examines the evolution of movement disorders over
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time in pediatric patients with thalamic tumors to determine the outcomes of those disorders. To our knowledge, this is the first study to report long-term outcome of movement disorders.
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Additionally, this study is unique in its attempt to identify patterns of thalamic nuclei involvement by tumor or surgical lesion (Table 2). We did not identify any specific pattern of injury to thalamic nuclei that contributed to movement disorder. Lehercy et al. also noted that the extent of thalamic nuclei injury in patients who had a stroke did not correlate with movement disorder.21 All nine patients with movement disorder in our study did have tumor involvement of the red nuclei, suggesting that this structure may have a central role. However, further studies will be needed to confirm this. 8
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Of the six types of movement disorder reported, postural tremor was the most common, followed by athetosis, ballism, dystonia, myoclonus, and resting tremor. Similarly, Krauss et al. found tremor to be the most common movement disorder in patients with thalamic or basal ganglia
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tumors.9 On the basis of retrospective application of severity scales, we demonstrated that most patients had a movement disorder of moderate intensity, and there was little or no meaningful improvement over time. The complete resolution of movement disorder seen in one patient is
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unexplainable. Elevated intracranial pressure may have contributed to the disorder, as symptoms improved after the patient received ventricular shunts. Paradoxical decline of KPS with stability
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or improvement of movement disorder in patients 2 and 5 likely represent tumor progression as both had malignant astrocytoma and both are deceased.
Radical resection by conventional craniotomy in the thalamus is associated with high morbidity and mortality; therefore, subtotal resection is commonly performed to obtain histopathological
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diagnosis and reduce tumor burden.22 Prior reports on movement disorder outcome mainly included patients with thalamic tumors who had undergone stereotactic biopsy and no extensive resection.23 The extent of tumor resection in our patients had a wider range, including
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stereotactic-guided biopsies, microsurgical subtotal resection, and gross total tumor resection.
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This range provided greater insight for relating the extent of surgical resection to the severity of movement disorder.
Most conventional medications administered to our patients to reduce movement disorder severity were reasonably well tolerated but did not provide clinically significant improvement. Pharmacological intervention was given to eight of nine patients, and four required more than one medication in an attempt to alleviate symptoms of movement disorder. Botox treatment also
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did not meaningfully improve symptoms, and patients elected to discontinue its use after a period of time.
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Conclusions In conclusion, movement disorder may develop in a small percentage of patients with unilateral or bilateral thalamic tumors. Our study did not demonstrate any specific pattern of surgical injury
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to the thalamic nuclei in patients with movement disorder, though tumor involvement of red nuclei may be relevant. Postsurgical movement disorder is a long-term problem that causes a fair
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amount of morbidity; thus, better medical management is needed. Prospective studies using newer imaging technology (i.e., functional MRI) to examine thalamic tumors and advances in assessing/treating movement disorders may help identify relations between movement disorders and lesions.
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among children with thalamic glial tumors. Pediatr Neurosurg. 1998;29: 29-35. Morel A. Stereotactic Atlas of the Human Thalamus and Basal Ganglia.New York, New
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PloS One. 2012;7: e46234.
Lehericy S, Grand S, Pollak P, et al. Clinical characteristics and topography of lesions in
movement disorders due to thalamic lesions. Neurology. 2001;57: 1055-1066. 22.
McGirr SJ, Kelly PJ, Scheithauer BW. Stereotactic resection of juvenile pilocytic
astrocytomas of the thalamus and basal ganglia. Neurosurgery. 1987;20: 447-452.
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23.
Krauss JK, Braus DF, Mohadjer M, Nobbe F, Mundinger F. Evaluation of the effect of
treatment on movement disorders in astrocytomas of the basal ganglia and the thalamus. J Neurol
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Neurosurg Psychiatry. 1993;56: 1113-1118. Disclosure
The authors report no conflict of interest concerning the materials or methods used in this study
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or the findings specified in this paper.
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Table 1. Clinical Characteristics of Pediatric Patients with Movement Disorders M, male; F, female; MD, movement disorder; Fm Hx MD, family history of movement disorder; Gr, grade; JPA, juvenile pilocytic astrocytoma; PT, postural tremor; RT, resting tremor; Bil, bilateral; UE, upper extremity; LE, lower extremity; L, left; R, right; A , Intensity modulated
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radiation therapy.
Table 2. The Severity and Outcomes of Movement Disorders related to Anatomical
A
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Locations of Postoperative Lesions
, Surgery causing movement disorder; B , post-biopsy hemorrhage involving all of thalamus;
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MRI, magnetic resonance imaging; mo, months; KPS, Karnofsky Performance Scale; ESRS, Extrapyramidal Symptom Rating Scale, which has possible scores of 0 (absent) to 6 (extremely severe); CGI-S, Clinical Global Impression of Severity for dystonia and dyskinesia, which has possible scores of 0 (absent) to 8 (extremely severe); Bx, stereotactic biopsy; STR, subtotal resection; GTR, gross total resection; R, right; L, left; Bil, bilateral; Thalamic nuclei: RN, red nucleus; SN, substantia nigra; LD, laterodorsal; MD, mediodorsal; CM, centromedian; lat thal,
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lateral thalamus; antr thal, anterior thalamus; P, pulvinar; VL, ventrolateral; GP, globus pallidus; f/u, follow-up; eval, evaluation; PT, postural tremor; RT, resting tremor; NA, severity score not
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available.
Figure Legend
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Figure 1. Postoperative Magnetic Resonance Imaging of Pediatric Patients with thalamic tumors
(A-I) Representative postoperative coronal T1 + contrast MRIs are shown for each patient
Acknowledgements
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included in the study.
The authors thank the St. Jude Division of Neuro-oncology’s Data Management Office for data
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collection and review.
Authors also thank Angela J. McArthur, Ph.D, ELS from the Department of Scientific Editing of
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St. Jude Children’s research Hospital for editing the manuscript for language and syntax. Sources of Support: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Authors and Contributors The first author of this manuscript, Zsila Sadighi, performed chart analysis, drafted the original manuscript, and edited the final manuscript. Raja Khan provided direct patient care, developed 14
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the concept, reviewed data, and edited the final manuscript. Other co-authors provided critical
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patient-specific data, radiographic images, and reports and assisted in writing.
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Table 1. Clinical Characteristics of Cases with Movement Disorder Case
Age at Age at Tumor Surgery Diagnosis (Years) (Years)
Age at Fm MD Hx Onset MD (Years)
Sex
MD Type
Tumor Histology
1
0.2
0.9
1.5
No
M
PT L UE, Dystonia L UE/LE
Gr 2 54 Gray Fibrillary Astrocytoma
2
3
3
3
No
F
PT L UE
3
9
9
10
No
F
4
8
8
8
No
5
6
6
6
6
7
7
7
11
8
9
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Radiation (conformal)
Chemotherapy Neuro Follow-up (Years)
10
Gr 3 59.4 Gray Astrocytoma RT/PT L UE, Gr 2 No Athetosis/Ballismus Fibrillary L UE/LE Astrocytoma
Yes
1
No
11
F
PT L UE, Ballismus L UE
Gr 3 54 Gray Astrocytoma
Yes
3
No
M
Ballismus R UE, L UE
Gr 3 59.4 Gray Astrocytoma
Yes
0.4
7
No
F
No
2.5
11
11
No
Athetosis/Ballismus Gr 3 54 GrayA L UE/LE, Astrocytoma Myoclonus L UE/LE, Dystonia L UE/LE, PT L UE PT/RT Bil UE/LE Gr 4 59.4 GrayA Astrocytoma
Yes
0.33
4
4
4
7
7
7
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Yes
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F
No
M
PT L UE, Athetosis JPA L UE, Myoclonus L UE
54 Gray
No
8
No
F
Athetosis R UE
59.4 Gray
Yes
0.83
15
Gr 2 Fibrillary
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Table 1. Clinical Characteristics of Cases with Movement Disorder
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Astrocytoma
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M, male; F, female; MD, movement disorder; Fm Hx MD, Family History of Movement Disorder; Gr, grade; JPA, juvenile pilocytic astrocytoma; PT, postural tremor; RT, resting tremor; Bil, bilateral; UE, upper extremity; LE, lower extremity; L, left; R, right, A , Intensity modulated radiation therapy.
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Table 2. Movement Disorder Severity Outcomes and Anatomical Location of Tumor and Surgery Time from Movement Disorder onset to before surgery (Months)
Time from after surgery to Movement Disorder onset (Months)
Surgery TypeA
2nd Surgery (Time from 1st surgery – (Years)
Post-op MRI surgical lesion
MRI tumor location
Movement Disorder Type
ESRS 1st visit
CGI-S 1st visit
1
11
--
Bx
STR (11.92)
R VL, P, MD
Bil RN, R>L LD, MD, CM, VL, RN, P, lat thal, antr thal, medial thal
PT L UE, Dystonia L UE/LE
PT 5, Dystonia 8 (4+4)
PT 4 Dystonia 4
2
--
1
Bx
NA
All R thalB
Bil thal, Bil RN, Bil SN
PT L UE
PT 5
3
--
4
GTR
NA
R CM, LD, lat thal
All R thal, RN
RT/PT L UE, Athetosis/ Ballismus L LE>UE
RT/PT 6, Athetosis/ Ballismus 8 (5+3)
4
--
0
Bx
STR (2.42)
R P, antr thalamus
All R thal, SN, RN
PT L UE, Ballismus L UE
5
--
2
Bx
NA
L P, MD
All L thal, RN, GP
6
--
0
STR
Bx (4.75)
All R thal, SN, RN, except antr thal
All R thal, RN, SN, except antr thal
7
--
2
Bx
NA
8
--
0
Bx
STR (0.1)
All L thal, SN, RN, except antr thal
R P, MD
All R thal, SN, RN, except antr thal
Time from Movement Disorder onset to last f/u (Years)
ESRS Last visit (Time from 1st eval)
CGI-S Last visit (Time from 1st eval)
KPS Last Visit (Time from 1st eval)
Overall outcome
9.8
PT 5, Dystonia 8 (10 years)
PT 4, Dystonia 4 (10 years)
80 (10 years)
No change
80
1
PT 5 (1 year)
PT 4 (1 year)
70 (1 year)
Worse
RT/PT 6 Dyskinesia 6
60
7
RT/PT 3, Athetosis/ Ballismus 10 (11 years)
RT/PT 3, Dyskinesia 4 (11 years)
80 (11 year)
Improved
PT 5, Ballismus 5
PT 6, Dyskinesia 6
70
3
PT 5, Ballismus 5 (3 years)
PT 4, Dyskinesia 4 (3 years)
70 (3 years)
Improved
Ballismus R UE/ LUE
6
5
70
0.2
0 (<1 year)
0 (<1 year)
Resolved
Athetosis/ Ballismus L UE/LE, Myoclonus L UE/LE, Dystonia L UE/LE, PT L UE, PT/RT Bil UE/LE
Athetosis/ Ballismus 10 (5+5), Dystonia 4 (2+2), PT 4
PT 3, Dyskinesia 3, Dystonia 3
90
4.5
Athetosis 3 (L UE), Dystonia 2 (L UE), PT 2 (2.5 years)
PT 3, Dyskinesia 3, Dystonia 3 (2.5 years)
50 (<1 year) 90 (2.5 years)
20 (5+5+5+5)
3
90
0.4
8 (<1 year)
3 (<1 year)
90 (<1 year)
Improved
PT L UE, Athetosis LUE, Myoclonus L
PT 5, Athetosis 5, Myoclonus
PT 5, Dyskinesia 5
80
11
PT 5, Dyskinesia 5, Myoclonus
PT 5, Dyskinesia 5 (8 years)
80 (8 years)
No change
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80
PT 3
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KPS 1st visit
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Case
16
Improved
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Table 2. Movement Disorder Severity Outcomes and Anatomical Location of Tumor and Surgery
--
3
STR
STR (0.33)
All L thal, except antr
All L thal, RN, SN, except antr thal
NA
Athetosis R UE
3
NA (8 years) 3
90
0.58
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9
UE
3 (<1 year)
90 (<1 year)
No change
, Surgery causing movement disorder; B , post-biopsy hemorrhage involving all of thalamus; MRI, magnetic resonance imaging; mo, months; KPS, Karnofsky Performance Scale; ESRS, Extrapyramidal Symptom Rating Scale, which has possible scores of 0 (absent) to 6 (extremely severe); CGI-S, Clinical Global Impression of Severity for dystonia and dyskinesia, which has possible scores of 0 (absent) to 8 (extremely severe); Bx, stereotactic biopsy; STR, subtotal resection; GTR, gross total resection; R, right; L, left; Bil, bilateral; Thalamic nuclei: RN, red nucleus; SN, substantia nigra; LD, laterodorsal; MD, mediodorsal; CM, centromedian; lat thal, lateral thalamus; antr thal, anterior thalamus; P, pulvinar; VL, ventrolateral; GP, globus pallidus; f/u, follow-up; eval, evaluation; PT, postural tremor; RT, resting tremor; NA, severity score not available.
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A
3 (<1 year)
26
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S0887-8994(16)30242-9
DOI:
10.1016/j.pediatrneurol.2016.08.012
Reference:
PNU 8969
To appear in:
Pediatric Neurology
Received Date: 12 April 2016 Revised Date:
11 August 2016
Accepted Date: 14 August 2016
Please cite this article as: Sadighi ZS, Zabrowski J, Boop FA, Broniscer A, Gajjar A, Khan RB, Clinical Characteristics and Long-term Outcomes of Movement Disorders in Childhood Thalamic Tumors, Pediatric Neurology (2016), doi: 10.1016/j.pediatrneurol.2016.08.012. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Clinical Characteristics and Long-term Outcomes of Movement Disorders in
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Childhood Thalamic Tumors
Zsila S. Sadighi MDa, Jennifer Zabrowski, RNa, Frederick A. Boop, MDb, Alberto Broniscer, MDc, Amar Gajjar, MDa,c, Raja B. Khan, MDa
Department of Pediatric Medicine, Division of Neurology, St. Jude Children’s Research
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a
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Hospital, Memphis, TN 38105, USA (email: ZS, [email protected]; JZ, [email protected]; RK, [email protected]) b
Department of Neurosurgery, University of Tennessee Health Science Center, Memphis, TN,
USA; Le Bonheur Neuroscience Institute, Le Bonheur Children's Hospital, Memphis, TN, USA; Semmes-Murphey Neurologic and Spine Institute, Memphis, TN, USA; Division of
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Neurosurgery, St Jude Children's Research Hospital, Memphis, TN 38105, USA (email: [email protected]) c
Department of Oncology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
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(email: AB, [email protected]; AG, [email protected])
Corresponding Author
Zsila S. Sadighi, MD, Division of Neurology, MS 135, 262 Danny Thomas Place, Memphis, TN 38105; Tel.: 901-595-8574; fax: 901-595-8548; e-mail: [email protected] Running Title: Movement Disorder in Thalamic Tumor Manuscript word count: 2,112
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Abstract
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Background: We studied the outcomes of movement disorders that were associated with childhood thalamic tumors.
Methods: We retrospectively reviewed 83 cases of childhood thalamic tumors treated at our
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institution from 1996 to 2013 to document the incidence and outcome of movement disorders. Magnetic resonance imaging was used to analyze the involvement of thalamic nuclei, and three
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instruments were used to rate the severity of the disorders.
Results: Nine (11%) patients had one or more of the following movement disorders: postural tremor, resting tremor, ballism, dystonia, myoclonus, and athetosis. Median age at tumor diagnosis was 7 years (range, 0.25-11 years), and that at movement disorder onset was 8 years
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(range, 1.5-11 years). Movement disorders developed at a median of 1.5 months (range, 0-4 months) after surgical resection. The severity of the disorders was either unchanged or slightly improved during follow-up. The red nuclei were the only thalamic structures that showed tumor
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involvement in all nine patients.
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Conclusions: No specific injury of the thalamic nuclei was associated with movement disorders in children with thalamic tumors, and the severity of those disorders did not change over time. Keywords: Thalamic tumors, childhood, movement disorder, outcome
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Introduction Thalamic tumors are uncommon in children and may comprise 0.84% to 5.2% of all intracranial childhood tumors.1 This discrepancy is due to difficulty in distinguishing between primary
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thalamic tumors (i.e., those that originate from the thalamus) and secondary thalamic tumors that arise from adjacent structures (i.e., caudate nuclei, brain stem, or pineal gland). These neoplasms are usually low-grade gliomas, but they can have histologic properties of grade III and IV
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astrocytoma. However, other tumor pathologies also have been reported.1, 2 Confirmation of diagnosis requires tumor biopsy and/or resection.3 Puget et al. found that patients with low-grade
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thalamic tumors experience better survival when more than 90% of the tumor is resected and the duration of symptoms is longer than 2 months.4 Bernstein et al. found that patients with thalamic malignancy survived approximately 1 year, regardless of the extent of resection.3 Bilateral thalamic tumors are even rarer and may have a worse prognosis.5 The clinical signs and
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symptoms of thalamic tumors can be burdensome and include sensory syndrome, motor disorders, oculomotor deficits, increased intracranial pressure, seizures, and movement disorders. Movement disorders occur infrequently in patients with thalamic tumors; their prevalence ranges
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from 1% to 33% in pediatric and adult studies.2, 3, 6, 7 Also, the data on the severity and outcome
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of movement disorders in these patients are inadequate. The symptoms of movement disorders are typically associated with large thalamic low-grade astrocytomas and most likely result from surgical injury or the tumor compressing the neurons or neuronal pathways in the thalamic relay center.8-11 Movement disorders reported in thalamic tumors include tremor, dystonia, chorea, ballism, and myoclonus.9 To our knowledge, no one has systematically correlated the anatomical locations of thalamic tumors or surgical lesions with the development of movement disorders and their outcomes. Therefore, we studied movement disorders in children with thalamic tumors 3
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and attempted to identify specific injuries to the thalamic nuclei that were associated with those disorders.
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Methods This retrospective review was approved by the St. Jude Institutional Review Board. Our query of the hospital’s neuro-oncology database for thalamic tumors identified 83 patients who were 18
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years or younger at diagnosis and treated at our institution from 1996 through 2013.
All 83 medical records were first reviewed by a study nurse to identify patients who may have
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had a movement disorder. Those charts were then reviewed by a study neurologist (RBK) blinded to the Magnetic resonance imaging (MRI) data to determine whether a movement disorder was present, and if so, its severity, response to therapy, and long-term outcome. MRI scans of all patients were reviewed by the other study neurologist (ZSS) blinded to the clinical
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data to define the surgical injury to thalamic nuclei and involvement with tumor. The anatomical locations of lesions seen on MRIs were assessed using a neuro-anatomy atlas with corresponding coronal, sagittal, and axial slices to identify nuclei-specific injuries.12 All tumors were
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histologically confirmed after stereotactic biopsy, subtotal resection, or gross total resection. Tumors were graded according to the classification system of the World Health Organization.13
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Assessment of Movement Disorders
The severity of movement disorders was determined using clinical information obtained by chart review and retrospectively applying the Karnofsky Performance Scale (KPS),14 Extrapyramidal Symptom Rating Scale (ESRS),15 and Clinical Global Impression of Severity (CGI-S)16 at the first and last follow-up visits. Our institution has had a systematic neurologic evaluation scale in place since 2001. All of the patients included in this study were seen by a neurologist, and most
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of them had findings recorded on paper or electronic chart based on the scale. All patients had at least one examination available in their charts. The KPS scale, which ranges from 0 (dead) to 100 (no evidence of motor weakness or impaired function), indicates the patient’s functional
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status. ESRS, which ranges from 0 (absent) to 6 (extremely severe), includes subscales for
assessing tremor (8 body parts summed to a maximum score of 48), dyskinesia (10 body parts summed to a maximum score of 60), and dystonia (7 items summed to a maximum score of
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42).15 CGI-S scores range from 0 (absent) to 8 (extremely severe), which assess overall severity
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of tremor, dyskinesia, and dystonia in disease.16
We defined tremor as rhythmic uncontrollable shaking of a body part. Postural tremor appeared when the patient was directed to sustain a posture, such as stretching one’s arms out. Dystonia was defined as a sustained contraction of a single or group of muscles. Myoclonus was defined as a sudden, single involuntary muscle jerk. Chorea was irregular, jerky spontaneous movements
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predominantly in proximal limb muscles, and athetosis was slower writhing movements predominantly in distal limb muscles. Finally, ballism was more explosive, jerky, and higher
Results
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amplitude flinging of a proximal limb(s).
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Clinical Characteristics
After chart review of 83 patients with thalamic tumors, we identified nine (11%) who experienced at least one type of movement disorder during the course of their illness. Median age at tumor diagnosis was 7 years (range, 0.25-11 years), and median age at movement disorder onset was 8 years (range, 1.5-11 years). Median time to first neurologic evaluation was 4 months (range, 1-36 months) after movement disorder onset, and median time to last follow-up was 3
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years (range, 0.2-11 years) after movement disorder onset. None of the patients had a family history of movement disorder, as determined by their answer to a question about whether any family member had ever been diagnosed with abnormal body movements or gait. All patients
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also had a normal early development.
Movement disorders included postural tremor (n=7), resting tremor (n=2), ballism (n=4),
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dystonia (n=2), myoclonus (n=2), athetosis (n=4): five patients had more than one type of
movement disorder present concurrently. Both low- and high-grade tumors were present in
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patients with movement disorders (Table 1). Movement disorder developed in eight patients at a median of 1.5 months (0-4 months) after surgery; one patient had movement disorder onset 11 months before surgery. The extent of tumor resection ranged from stereotactic biopsy (n=5), to subtotal resection (n=3), to complete tumor resection (n=1). Conformal radiation therapy (5459.4 Gy) was used as an adjuvant treatment in eight patients at a median time of 2.5 years (range,
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0.83-5 years) after tumor diagnosis. Six of the eight patients received adjuvant chemotherapy as well. Four patients required a second surgery at a median time of 4 years (range, 1-12 years) after the first; this procedure did not influence the intensity or morphology of the movement
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disorder in any patient (Table 1). Two patients had bithalamic tumors, and seven had unilateral
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tumors. In the latter group, the movement disorder was contralateral to the tumor site. Six patients had tumors confined to the thalamus, whereas three had tumor extension into surrounding structures (i.e., corpus callosum, lateral ventricle, basal ganglia, internal capsule, and midbrain) (Tables 1-2).
The postoperative MRIs showed surgical lesions in the pulvinar (n=4), mediodorsal (n=2), ventrolateral (n=2), centromedian (n=1), anterior (n=1), and laterodorsal (n=1) regions of the thalamus and in the substantia nigra (n=1), and red nucleus (n=1) (Figure 1). Of the seven 6
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unilateral thalamic tumors, four invaded the entire thalamus, and three invaded all but the anterior region. All nine patients had tumors involving the red nucleus, and six had tumors involving the substantia nigra (Table 2). Post-operative intra tumoral hemorrhage developed in
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one patient 3 weeks after the biopsy. Movement disorder appeared a week after the hemorrhage in this patient.
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Movement Disorder Severity and Outcomes
Postural tremor was unilateral and in one extremity in six patients; it was bilateral in one patient
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and involved both the upper and lower extremities. Both athetosis and ballism involved one extremity in two patients and involved ipsilateral upper and lower extremities in four patients. Myoclonus was present in one upper limb in one patient and in one upper and one lower extremity in the other. Resting tremor was unilateral in one patient and bilateral in the other. The two patients with bilateral thalamic tumors and involvement of the red nucleus and substantia
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nigra had unilateral postural tremor only.
The KPS score remained relatively stable over time in patients with movement disorder. The
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median KPS score was 80 (range, 60-90) at initial visit and was unchanged at 80 (range, 50-90) at the last follow-up. Tremor severity did not change over time, as measured by ESRS and CGI-S
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(Table 2). We saw some improvement of dystonia with ESRS but not with CGI-S. Athetosis and ballism, both defined as dyskinesia, improved over time, as measured by ESRS and CGI-S. All ESRS improvements were modest and most likely not clinically significant as CGI-S scores did not improve meaningfully (Table 2). We did not recognize any pattern of tumor involvement of thalamic nuclei by surgical injury. By last follow-up, symptoms showed no change over time in three patients: one patient had postural
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tremor and dystonia; one had postural tremor, athetosis, and myoclonus; and one had athetosis. One patient experienced worsening of postural tremor, and another had complete resolution of ballism. Finally, four patients showed improvement in their movement disorder: one patient had
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resting tremor and postural tremor, athetosis, and ballism; one had postural tremor and ballism; one had athetosis, ballism, dystonia, and postural tremor; and one had resting tremor and postural
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tremor.
Eight of nine patients received various pharmacological interventions [e.g., steroids, gamma-
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amino butyric acid (GABA) A and B agonists, anti-seizure medications, alpha-2 agonists, anticholinergics, dopa agonists, calcium channel blockers, and botulinum toxin injections], and four received multiple medications. Although such treatments resulted in some initial benefit, improvement was not clinically meaningful. Therefore, patients elected to discontinue the
Discussion
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treatment.
This retrospective review is unique in that it examines the evolution of movement disorders over
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time in pediatric patients with thalamic tumors to determine the outcomes of those disorders. To our knowledge, this is the first study to report long-term outcome of movement disorders.
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Additionally, this study is unique in its attempt to identify patterns of thalamic nuclei involvement by tumor or surgical lesion (Table 2). We did not identify any specific pattern of injury to thalamic nuclei that contributed to movement disorder. Lehercy et al. also noted that the extent of thalamic nuclei injury in patients who had a stroke did not correlate with movement disorder.21 All nine patients with movement disorder in our study did have tumor involvement of the red nuclei, suggesting that this structure may have a central role. However, further studies will be needed to confirm this. 8
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Of the six types of movement disorder reported, postural tremor was the most common, followed by athetosis, ballism, dystonia, myoclonus, and resting tremor. Similarly, Krauss et al. found tremor to be the most common movement disorder in patients with thalamic or basal ganglia
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tumors.9 On the basis of retrospective application of severity scales, we demonstrated that most patients had a movement disorder of moderate intensity, and there was little or no meaningful improvement over time. The complete resolution of movement disorder seen in one patient is
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unexplainable. Elevated intracranial pressure may have contributed to the disorder, as symptoms improved after the patient received ventricular shunts. Paradoxical decline of KPS with stability
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or improvement of movement disorder in patients 2 and 5 likely represent tumor progression as both had malignant astrocytoma and both are deceased.
Radical resection by conventional craniotomy in the thalamus is associated with high morbidity and mortality; therefore, subtotal resection is commonly performed to obtain histopathological
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diagnosis and reduce tumor burden.22 Prior reports on movement disorder outcome mainly included patients with thalamic tumors who had undergone stereotactic biopsy and no extensive resection.23 The extent of tumor resection in our patients had a wider range, including
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stereotactic-guided biopsies, microsurgical subtotal resection, and gross total tumor resection.
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This range provided greater insight for relating the extent of surgical resection to the severity of movement disorder.
Most conventional medications administered to our patients to reduce movement disorder severity were reasonably well tolerated but did not provide clinically significant improvement. Pharmacological intervention was given to eight of nine patients, and four required more than one medication in an attempt to alleviate symptoms of movement disorder. Botox treatment also
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did not meaningfully improve symptoms, and patients elected to discontinue its use after a period of time.
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Conclusions In conclusion, movement disorder may develop in a small percentage of patients with unilateral or bilateral thalamic tumors. Our study did not demonstrate any specific pattern of surgical injury
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to the thalamic nuclei in patients with movement disorder, though tumor involvement of red nuclei may be relevant. Postsurgical movement disorder is a long-term problem that causes a fair
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amount of morbidity; thus, better medical management is needed. Prospective studies using newer imaging technology (i.e., functional MRI) to examine thalamic tumors and advances in assessing/treating movement disorders may help identify relations between movement disorders and lesions.
1.
Di Rocco C, Iannelli A. Bilateral thalamic tumors in children. Childs Nerv Syst. 2002;18:
440-444.
Martinez-Lage JF, Perez-Espejo MA, Esteban JA, Poza M. Thalamic tumors: clinical
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central nervous system. Acta Neuropathol. 2007;114: 97-109. 11
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14.
Mor V, Laliberte L, Morris JN, Wiemann M. The Karnofsky Performance Status Scale.
An examination of its reliability and validity in a research setting. Cancer. 1984;53: 2002-2007. Chouinard G, Margolese HC. Manual for the Extrapyramidal Symptom Rating Scale
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Guy W. ECDEU Assessment Manual for Psychopharmacology —Revised. Rockville,
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MD, U.S. Department of Health, Education, and Welfare, Public Health Service, Alcohol, Drug Abuse, and Mental Health Administration, NIMH DHEW Publ; 1976.
Cuccia V, Monges J. Thalamic tumors in children. Childs Nerv Syst. 1997;13: 514-520;
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discussion 521. 18.
Reardon DA, Gajjar A, Sanford RA, et al. Bithalamic involvement predicts poor outcome
19.
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among children with thalamic glial tumors. Pediatr Neurosurg. 1998;29: 29-35. Morel A. Stereotactic Atlas of the Human Thalamus and Basal Ganglia.New York, New
York: CRC Press. Informa Healthcare; 2007.
Contarino MF, Groot PF, van der Meer JN, et al. Is there a role for combined EMG-fMRI
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in exploring the pathophysiology of essential tremor and improving functional neurosurgery?
21.
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PloS One. 2012;7: e46234.
Lehericy S, Grand S, Pollak P, et al. Clinical characteristics and topography of lesions in
movement disorders due to thalamic lesions. Neurology. 2001;57: 1055-1066. 22.
McGirr SJ, Kelly PJ, Scheithauer BW. Stereotactic resection of juvenile pilocytic
astrocytomas of the thalamus and basal ganglia. Neurosurgery. 1987;20: 447-452.
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23.
Krauss JK, Braus DF, Mohadjer M, Nobbe F, Mundinger F. Evaluation of the effect of
treatment on movement disorders in astrocytomas of the basal ganglia and the thalamus. J Neurol
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Neurosurg Psychiatry. 1993;56: 1113-1118. Disclosure
The authors report no conflict of interest concerning the materials or methods used in this study
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or the findings specified in this paper.
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Table 1. Clinical Characteristics of Pediatric Patients with Movement Disorders M, male; F, female; MD, movement disorder; Fm Hx MD, family history of movement disorder; Gr, grade; JPA, juvenile pilocytic astrocytoma; PT, postural tremor; RT, resting tremor; Bil, bilateral; UE, upper extremity; LE, lower extremity; L, left; R, right; A , Intensity modulated
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radiation therapy.
Table 2. The Severity and Outcomes of Movement Disorders related to Anatomical
A
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Locations of Postoperative Lesions
, Surgery causing movement disorder; B , post-biopsy hemorrhage involving all of thalamus;
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MRI, magnetic resonance imaging; mo, months; KPS, Karnofsky Performance Scale; ESRS, Extrapyramidal Symptom Rating Scale, which has possible scores of 0 (absent) to 6 (extremely severe); CGI-S, Clinical Global Impression of Severity for dystonia and dyskinesia, which has possible scores of 0 (absent) to 8 (extremely severe); Bx, stereotactic biopsy; STR, subtotal resection; GTR, gross total resection; R, right; L, left; Bil, bilateral; Thalamic nuclei: RN, red nucleus; SN, substantia nigra; LD, laterodorsal; MD, mediodorsal; CM, centromedian; lat thal,
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lateral thalamus; antr thal, anterior thalamus; P, pulvinar; VL, ventrolateral; GP, globus pallidus; f/u, follow-up; eval, evaluation; PT, postural tremor; RT, resting tremor; NA, severity score not
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available.
Figure Legend
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Figure 1. Postoperative Magnetic Resonance Imaging of Pediatric Patients with thalamic tumors
(A-I) Representative postoperative coronal T1 + contrast MRIs are shown for each patient
Acknowledgements
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included in the study.
The authors thank the St. Jude Division of Neuro-oncology’s Data Management Office for data
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collection and review.
Authors also thank Angela J. McArthur, Ph.D, ELS from the Department of Scientific Editing of
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St. Jude Children’s research Hospital for editing the manuscript for language and syntax. Sources of Support: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Authors and Contributors The first author of this manuscript, Zsila Sadighi, performed chart analysis, drafted the original manuscript, and edited the final manuscript. Raja Khan provided direct patient care, developed 14
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the concept, reviewed data, and edited the final manuscript. Other co-authors provided critical
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patient-specific data, radiographic images, and reports and assisted in writing.
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Table 1. Clinical Characteristics of Cases with Movement Disorder Case
Age at Age at Tumor Surgery Diagnosis (Years) (Years)
Age at Fm MD Hx Onset MD (Years)
Sex
MD Type
Tumor Histology
1
0.2
0.9
1.5
No
M
PT L UE, Dystonia L UE/LE
Gr 2 54 Gray Fibrillary Astrocytoma
2
3
3
3
No
F
PT L UE
3
9
9
10
No
F
4
8
8
8
No
5
6
6
6
6
7
7
7
11
8
9
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Radiation (conformal)
Chemotherapy Neuro Follow-up (Years)
10
Gr 3 59.4 Gray Astrocytoma RT/PT L UE, Gr 2 No Athetosis/Ballismus Fibrillary L UE/LE Astrocytoma
Yes
1
No
11
F
PT L UE, Ballismus L UE
Gr 3 54 Gray Astrocytoma
Yes
3
No
M
Ballismus R UE, L UE
Gr 3 59.4 Gray Astrocytoma
Yes
0.4
7
No
F
No
2.5
11
11
No
Athetosis/Ballismus Gr 3 54 GrayA L UE/LE, Astrocytoma Myoclonus L UE/LE, Dystonia L UE/LE, PT L UE PT/RT Bil UE/LE Gr 4 59.4 GrayA Astrocytoma
Yes
0.33
4
4
4
7
7
7
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Yes
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F
No
M
PT L UE, Athetosis JPA L UE, Myoclonus L UE
54 Gray
No
8
No
F
Athetosis R UE
59.4 Gray
Yes
0.83
15
Gr 2 Fibrillary
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Table 1. Clinical Characteristics of Cases with Movement Disorder
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Astrocytoma
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M, male; F, female; MD, movement disorder; Fm Hx MD, Family History of Movement Disorder; Gr, grade; JPA, juvenile pilocytic astrocytoma; PT, postural tremor; RT, resting tremor; Bil, bilateral; UE, upper extremity; LE, lower extremity; L, left; R, right, A , Intensity modulated radiation therapy.
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Table 2. Movement Disorder Severity Outcomes and Anatomical Location of Tumor and Surgery Time from Movement Disorder onset to before surgery (Months)
Time from after surgery to Movement Disorder onset (Months)
Surgery TypeA
2nd Surgery (Time from 1st surgery – (Years)
Post-op MRI surgical lesion
MRI tumor location
Movement Disorder Type
ESRS 1st visit
CGI-S 1st visit
1
11
--
Bx
STR (11.92)
R VL, P, MD
Bil RN, R>L LD, MD, CM, VL, RN, P, lat thal, antr thal, medial thal
PT L UE, Dystonia L UE/LE
PT 5, Dystonia 8 (4+4)
PT 4 Dystonia 4
2
--
1
Bx
NA
All R thalB
Bil thal, Bil RN, Bil SN
PT L UE
PT 5
3
--
4
GTR
NA
R CM, LD, lat thal
All R thal, RN
RT/PT L UE, Athetosis/ Ballismus L LE>UE
RT/PT 6, Athetosis/ Ballismus 8 (5+3)
4
--
0
Bx
STR (2.42)
R P, antr thalamus
All R thal, SN, RN
PT L UE, Ballismus L UE
5
--
2
Bx
NA
L P, MD
All L thal, RN, GP
6
--
0
STR
Bx (4.75)
All R thal, SN, RN, except antr thal
All R thal, RN, SN, except antr thal
7
--
2
Bx
NA
8
--
0
Bx
STR (0.1)
All L thal, SN, RN, except antr thal
R P, MD
All R thal, SN, RN, except antr thal
Time from Movement Disorder onset to last f/u (Years)
ESRS Last visit (Time from 1st eval)
CGI-S Last visit (Time from 1st eval)
KPS Last Visit (Time from 1st eval)
Overall outcome
9.8
PT 5, Dystonia 8 (10 years)
PT 4, Dystonia 4 (10 years)
80 (10 years)
No change
80
1
PT 5 (1 year)
PT 4 (1 year)
70 (1 year)
Worse
RT/PT 6 Dyskinesia 6
60
7
RT/PT 3, Athetosis/ Ballismus 10 (11 years)
RT/PT 3, Dyskinesia 4 (11 years)
80 (11 year)
Improved
PT 5, Ballismus 5
PT 6, Dyskinesia 6
70
3
PT 5, Ballismus 5 (3 years)
PT 4, Dyskinesia 4 (3 years)
70 (3 years)
Improved
Ballismus R UE/ LUE
6
5
70
0.2
0 (<1 year)
0 (<1 year)
Resolved
Athetosis/ Ballismus L UE/LE, Myoclonus L UE/LE, Dystonia L UE/LE, PT L UE, PT/RT Bil UE/LE
Athetosis/ Ballismus 10 (5+5), Dystonia 4 (2+2), PT 4
PT 3, Dyskinesia 3, Dystonia 3
90
4.5
Athetosis 3 (L UE), Dystonia 2 (L UE), PT 2 (2.5 years)
PT 3, Dyskinesia 3, Dystonia 3 (2.5 years)
50 (<1 year) 90 (2.5 years)
20 (5+5+5+5)
3
90
0.4
8 (<1 year)
3 (<1 year)
90 (<1 year)
Improved
PT L UE, Athetosis LUE, Myoclonus L
PT 5, Athetosis 5, Myoclonus
PT 5, Dyskinesia 5
80
11
PT 5, Dyskinesia 5, Myoclonus
PT 5, Dyskinesia 5 (8 years)
80 (8 years)
No change
SC
80
PT 3
M AN U
TE D
EP
AC C L VL, CM
KPS 1st visit
RI PT
Case
16
Improved
ACCEPTED MANUSCRIPT
Table 2. Movement Disorder Severity Outcomes and Anatomical Location of Tumor and Surgery
--
3
STR
STR (0.33)
All L thal, except antr
All L thal, RN, SN, except antr thal
NA
Athetosis R UE
3
NA (8 years) 3
90
0.58
RI PT
9
UE
3 (<1 year)
90 (<1 year)
No change
, Surgery causing movement disorder; B , post-biopsy hemorrhage involving all of thalamus; MRI, magnetic resonance imaging; mo, months; KPS, Karnofsky Performance Scale; ESRS, Extrapyramidal Symptom Rating Scale, which has possible scores of 0 (absent) to 6 (extremely severe); CGI-S, Clinical Global Impression of Severity for dystonia and dyskinesia, which has possible scores of 0 (absent) to 8 (extremely severe); Bx, stereotactic biopsy; STR, subtotal resection; GTR, gross total resection; R, right; L, left; Bil, bilateral; Thalamic nuclei: RN, red nucleus; SN, substantia nigra; LD, laterodorsal; MD, mediodorsal; CM, centromedian; lat thal, lateral thalamus; antr thal, anterior thalamus; P, pulvinar; VL, ventrolateral; GP, globus pallidus; f/u, follow-up; eval, evaluation; PT, postural tremor; RT, resting tremor; NA, severity score not available.
AC C
EP
TE D
M AN U
SC
A
3 (<1 year)
26
AC C
EP
TE D
M AN U
SC
RI PT
ACCEPTED MANUSCRIPT