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Stereotypical Movements and Frontotemporal Dementia Mario F. Mendez, MD, PhD,1,2* Jill S. Shapira, RN, PhD,1 and Bruce L. Miller, MD3 1
Department of Neurology, University of California at Los Angeles, Los Angeles, California, USA 2 Department of Psychiatry & Biobehavioral Sciences, University of California at Los Angeles and Veterans Administration Greater Los Angeles Healthcare Center, Los Angeles, California, USA 3 Department of Neurology, University of California at San Francisco, San Francisco, California, USA Abstract: Stereotypical movements are characteristic of autism or mental retardation but can also occur in patients with dementia, particularly frontotemporal dementia (FTD). In this study, we administered the Abnormal Involuntary Movement Scale (AIMS) to 18 patients with FTD and to 18 patients with the most common form of dementia, Alzheimer’s disease (AD). The AIMS scores were gathered at the initial presentation of patients who had not received antipsychotic medications. Compared to the AD patients, the FTD patients had significantly more stereotypical movements, including frequent rubbing behaviors and some selfinjurious acts. All the FTD patients with stereotypical movements had compulsive-like behaviors, suggesting a similar pathophysiologic cause, and most had a decrease in their stereotypical movements with the administration of sertraline, a serotonin selective reuptake inhibitor. © 2005 Movement Disorder Society Key words: stereotypical movements; stereotypies; frontotemporal dementia; compulsions
Stereotypical movements are repetitive, coordinated movements that resemble purposeful acts but have no clear purpose.1 They differ from tics, which are usually more abrupt and driven, and from compulsions, which are usually more complex routines and rituals. Stereotypical movements occur in almost all persons with autism, the majority of institutionalized adults with mental retardation, and many schizophrenics.2,3 Clinicians may not appreciate that these movements occur in patients with dementia. Clinical reports suggest that stereotypical movements are more prominent in frontotemporal dementia (FTD) compared to other dementing illnesses.
*Correspondence to: Dr. Mario F. Mendez, Neurobehavior Unit (691/116AF), VA Greater Los Angeles Healthcare Center, 11301 Wilshire Blvd., Los Angeles, CA. 90073. E-mail:
[email protected] Received 30 July 2004; Revised 5 October 2004; Accepted 12 November 2004 Published online 22 March 2005 in Wiley InterScience (www. interscience.wiley.com). DOI: 10.1002/mds.20465
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FTD is a disorder characterized by neuropsychiatric symptoms, including alterations in social interpersonal behavior, personal regulation, empathy, and insight.4,5 Investigators have documented a range of repetitive behaviors in FTD, usually described as compulsive acts.6 –9 This study evaluated the frequency and nature of stereotypical movements in patients with FTD compared to those in patients with AD. This study further assessed the relationship of these movements to compulsive behaviors and their response to therapy with a serotonergic agent.10 SUBJECTS AND METHODS Subjects The participants in this study presented for evaluation to university-affiliated clinics specializing in dementing disorders. The patients were community-based, moderately impaired persons who underwent a comprehensive neurobehavioral evaluation, laboratory assessment, and neuroimaging. The study excluded patients on medications, particularly antipsychotic drugs, or with medical, neurologic, or psychiatric disorders that could otherwise account for stereotypical movements. All 18 FTD patients included in this study presented with behavioral complaints plus symptoms of loss of social or personal awareness, disinhibited behavior, or disengagement and apathy. These were patients who presented sequentially over a 2.5-year period, met consensus criteria for FTD,4 and gave consent to participate in research. Functional neuroimaging with single photon emission computer tomography (SPECT) or positron emission tomography (PET) confirmed the diagnosis. The clinical diagnosis of FTD required the presence of frontally predominant, anterior temporally predominant, or frontotemporal changes on SPECT or PET.11 An additional 18 patients with Alzheimer’s disease (AD) were included for comparison. These patients met National Institute of Neurological and Communicative Disorders-Alzheimer’s Disease and Related Disorders (NINCDS-ADRDA) criteria for clinically probable AD after completing a diagnostic evaluation.12 To match the FTD patients, an effort was made to select AD patients who had an early age of onset of disease. The FTD and AD patients were not specifically matched on any other variable. Methods On initial presentation, the FTD and AD patients were evaluated with several scales and inventories and caregivers were questioned for the presence of compulsions. The patients underwent two scales of dementia severity,
STEREOTYPICAL MOVEMENTS AND FTD TABLE 1. Frontotemporal dementia vs. Alzheimer’s disease: patient characteristics
Number Sex (M/F) Age (yr) Education (yr) MMSE CDR Patients with compulsions on checklist (n)a
FTD
AD
18 10/8 61.82 ⫾ 5.31 14.54 ⫾ 4.23 22.33 ⫾ 7.60 1.52 ⫾ 1.01
18 8/10 66.10 ⫾ 7.49 13.78 ⫾ 3.39 20.02 ⫾ 4.02 1.89 ⫾ 1.38
12
2
a Significant differences, 2 ⫽ 9.47, P ⬍ 0.01. FTD, frontotemporal dementia; AD, Alzheimer’s disease; MMSE, Mini-Mental State Examination; CDR, Clinical Dementia Rating Scale.
the Mini-Mental State Examination (MMSE) and the Clinical Dementia Rating Scale (CDR).13,14 These scales were administered concurrent with the initial clinical interview and examination. Additionally, the examiner completed a Compulsive Behavior Checklist modified from the Children’s Yale–Brown Obsessive Compulsive Scale and based on the caregiver’s interview.15 The participants were evaluated with the Abnormal Involuntary Movements Scale (AIMS).16 This instrument involves observing patients for abnormal movements while they are sitting in a chair, while opening their mouths and protruding their tongues, finger tapping, flexing their arms, standing up, extending their arms, and walking. Reiterative speech, such as palilalia, echolalia, or repetitive utterances, were not included as stereotypical movements. The FTD patients with stereotypical movements were treated with sertraline, a selective serotonin reuptake inhibitor (SSRI), for 6 months and re-evaluated with the AIMS. RESULTS There were no statistically significant differences between the FTD and the AD groups on male:female ratio and education or on MMSE and CDR scores (see Table
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1). The FTD patients, however, were younger than the AD patients, but this finding did not reach statistical significance. The FTD patients also had significantly more compulsive behaviors on the intake checklist, including counting steps, repetitive trips to the bathroom without need, cleaning activities, and so on. Of the 18 FTD patients, 8 had stereotypical behaviors (44.%), compared to 1 of the 18 AD patients (5.6%; ⌾2 ⫽ 5.33; df ⫽ 1; P ⬍ 0.05). There were significant differences between the FTD patients and the AD patients on the AIMS total scores (see Table 2). Among the 8 FTD patients with stereotypical movements, there was a significant decline in total AIMS score after 6 months of treatment with sertraline at low doses ranging from 50 to 100 mg q.d. All FTD patients with stereotypical movements also had compulsive behaviors, although an additional 4 FTD patients had compulsive-like behaviors without stereotypical movements. The stereotypical movements among the FTD patients are described in Table 3. A comparison of neuropsychological and neuroimaging findings did not reveal statistically significant differences between the FTD patients with and without stereotypical behaviors. Nonetheless, all the FTD patients with stereotypies had involvement of the orbitofrontal areas along with other frontotemporal regions on PET and SPECT scans compared to only 6 of the FTD patients without stereotypies. DISCUSSION These FTD patients illustrate a problem that has not received much attention, i.e., stereotypies in dementia. Stereotypical movements are patterned, repetitive, purposeless movements that are performed the same way each time.1 They commonly occur with autism, mental retardation, Tourette’s syndrome, tardive dyskinesia, obsessive– compulsive disorder (OCD), and schizophrenia
TABLE 2. Frontotemporal dementia vs. Alzheimer’s disease: abnormal involuntary movement scale FTD patients Pre-Rx Facial, oral movements Extremity movements Trunk movements Global judgments Dental status Total score FTD with stereotypical movements: Total score
Post-Rx
1.50 ⫾ 2.64 1.07 ⫾ 1.86 0.33 ⫾ 1.03 2.61 ⫾ 3.07 0.16 ⫾ 0.51 5.67 ⫾ 6.32 12.38 ⫾ 2.07
8.00 ⫾ 3.38
AD patients
Significance
0.17 ⫾ 0.71 0 0 0.50 ⫾ 2.12 0.33 ⫾ 1.03 1.00 ⫾ 2.79
n.s. n.s. n.s. n.s. n.s. t ⫽ 8.68; P ⬍ 0.01 t ⫽ 3.12; P ⬍ 0.01
The patients did not have significant dental problems. FTD, frontotemporal dementia; AD, Alzheimer’s disease; Pre-Rx, before initiation of sertraline; Post-Rx, After 6 months of treatment with sertraline.
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TABLE 3. Stereotypical movements among 18 patients with frontotemporal dementia Number
Type
2a 1a 1a 2a 1a 1 1a 1a 1a 1
Rubbing legs or arms Rubbing face Rubbing another part of body Picking at fingertips to excoriation Clapping thighs Swaying of body and rocking back and forth Movements of eyebrows Movement of mouth up into a fixed grin or other grimaces Pursing of lips Blowing movements and sounds
a
Includes a patient with more than one stereotypical movement
and may result from cocaine or amphetamine abuse or levodopa therapy.1,2,17 The FTD patients in this study presented with significantly more stereotypical movements than did those with AD. Their stereotypical movements occurred with concomitant compulsions and, similar to compulsions, diminished with SSRI therapy.10 Clinicians distinguish stereotypical movements from motor tics and compulsions.1 All of these conditions may repeat themselves nearly continuously or may have long periods between occurrences. Both stereotypies and tics are purposeless movements. Stereotypies, however, are usually less abrupt than tics and lack an irresistible urge to execute the movement and a transient relief afterward.18 Stereotypical movements are further distinguishable from compulsions, which are purposeful behaviors that are performed in response to an obsession or to eliminate discomfort. In addition, compulsions can be complex behavioral rituals or activities. Despite these distinctions, it is not always possible to distinguish between these repetitive behaviors. Repetitive motor behaviors are common in FTD.19 Nearly 80% of pathologically proven cases demonstrate repetitive behaviors ranging from motor stereotypies to OCD.6 Compared to AD patients, FTD patients are four to five times more likely to have compulsive-like behavior.8 Specific compulsions in FTD patients include typical counting and cleaning rituals, repetitive trips to the bathroom, and hoarding activity.7 Some FTD patients have had self-injurious behaviors such as trichotillomania and picking at fingers to the point of excoriation.20 Stereotypies and compulsions may be a continuum of repetitive movements that result from orbitofrontal and caudate injury. In OCD, metabolic activity is increased in orbitofrontal cortex and caudate nuclei.21–23 In FTD, neuroimaging and neuropathological studies indicate that compulsive behavior results from combined damage to the frontal lobe and the basal ganglia, particularly the caudate nuclei.6,9 Because the basal ganglia modulate the
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release or inhibition of movements, injury to the frontal– striatal circuits that traverse the caudate nuclei may results in an inability to inhibit existing urges to perform repetitive movements or to prevent stimulus-driven behavior.7,9,24 Both OCD and FTD patients have decreased response suppression and behavioral inhibition.25,26 Although our numbers were small, all the FTD patients with stereotypies had involvement of the orbitofrontal areas on PET and SPECT scans, suggesting injury to the frontal–striatal circuits emanating from this region. In conclusion, stereotypical movements are common in FTD. The presence of these movements can help distinguish patients with FTD from those with the much more common AD. This preliminary study indicates that treatment can be successfully aimed at the serotonergic system. Much more work is needed, particularly given the possible selection bias in our FTD sample and the lack of blinded investigation of the treatment of their stereotypies. Future work can also explore whether FTD patients with stereotypical movements have evidence of pathological involvement of the caudate nuclei, as well as the frontal lobes. Acknowledgments: This research was supported in part by the National Institute on Aging (AG19724-01), the UCLA Alzheimer’s Disease Center, and the State of California.
REFERENCES 1. Tan A, Salgado M, Fahn S. The characterization and outcome of stereotypical movements in nonautistic children. Mov Disord 1997;12:47–52. 2. Castellanos FX, Ritchie GF, Marsh WL, Rapoport JL. DSM-IV stereotypical movement disorder: persistence of stereotypies of infancy in intellectually normal adolescents and adults. J Clin Psychiatry 1996;57:116 –122. 3. Bodfish JW, Crawford TW, Powell SB, Parker DE, Golden RN, Lewis MH. Compulsions in adults with mental retardation: prevalence, phenomenology, and comorbidity with stereotypy and selfinjury. Am J Ment Retard 1995;100:183–192. 4. Neary D, Snowden JS, Gustafson L, et al. Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology 1998;51:1546 –1554. 5. Mendez MF, Perryman KM. Neuropsychiatric features of frontotemporal dementia. Evaluation of consensus criteria and review. J Neuropsychiatry Clin Neurosci 2002;14:424 – 429. 6. Ames D, Cummings JL, Wirshing WC, et al. Repetitive and compulsive behavior in frontal lobe degenerations. J Neuropsychiatry Clin Neurosci 1994;6:100 –113. 7. Mendez MF, Perryman KM, Miller BL, Schiffer JR, Cummings JL. Compulsive behaviors as presenting symptoms of frontotemporal dementia. J Geriatric Psychiatry Neurol 1997;10:154 –157. 8. Miller BL, Darby AL, Swartz JR, et al. Dietary changes, compulsions and sexual behavior in frontotemporal degeneration. Dementia 1995:6:195–199. 9. Tonkonogy JM, Smith TW, Barreira PJ. Obsessive-compulsive disorders in Pick’s disease. J Neuropsychiatry Clin Neurosci 1994; 6:176 –180. 10. Swartz JR, Miller BL, Lesser IM, Darby AL. Frontotemporal dementia: treatment response to serotonin selective receptor inhibitors. J Clin Psychiatry 1997;58:212–216.
AMELIORATION OF POSTHYPOXIC MYOCLONUS BY Xyrem 11. Read S, Miller BL, Mena I, et al. SPECT in dementia: clinical and pathological correlation. J Am Geriatr Soc 1995;43:1243–1247. 12. McKhann G, Drachman D, Folstein M, et al. Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA work group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s disease. Neurology 1984;34:939 –944. 13. Folstein MF, Folstein SE, McHugh PR. Mini-Mental State: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:89 –98. 14. Hughes CP, Berg L, Danzinger WL, Coben LA, Martin RL. A new clinical scale for the staging of dementia. Br J Psychiatry 1982; 140:566 –572. 15. Steketee G, Freund B. Compulsive activity checklist: further psychometric analysis and revision. Behav Psychother 1993;21:13– 25. 16. Munetz MR, Benjamin S. How to examine patients using the Abnormal Involuntary Movements Scale. Hosp Comm Psychiatry 1988;39:1172–1177. 17. Mendez MF, Mirea A. Adult head-banging and stereotypic movement disorders. Mov Disord 1998;13:825– 828. 18. Lees AJ. Facial mannerisms and tics. Adv Neurol 1988;49:255– 261. 19. Shigenobu K, Ikeda M, Fukuhara R, et al. The Stereotypy Rating Inventory for frontotemporal lobar degeneration. Psychiatry Res 2002;110:175–187. 20. Mendez MF, Bagart B, Edwards-Lee T. Self-injurious behavior in frontotemporal dementia. Neurocase 1997;3:231–236. 21. Breiter HC, Rauch SL, Kwong KK, et al. Functional magnetic resonance imaging of symptom provocation in obsessive-compulsive disorder. Arch Gen Psychiatry 1996;53:595– 606. 22. McGuire PK, Bench CJ, Frith CD, et al. Functional anatomy of obsessive-compulsive phenomena. Br J Psychiatry 1994;164:459 – 468. 23. Simpson S, Baldwin B. Neuropsychiatry and SPECT of an acute obsessive-compulsive syndrome patient. Br J Psychiatry 1995;166: 390 –392. 24. Cummings JL. Frontal-subcortical circuits and human behavior. Arch Neurol 1993;50:873– 880. 25. Berthier ML, Kulisevsky J, Gironell A, Heras JA. Obsessivecompulsive disorder associated with brain lesions: clinical phenomenology, cognitive function, and anatomic correlates. Neurology 1996;47:353–361. 26. Rosenberg DR, Dick EL, O’Hearn KM, Sweeney JA. Responseinhibition deficits in obsessive-compulsive disorder: an indicator of dysfunction in frontostriatal circuits. J Psychiatry Neurosci 1997;22:29 –38.
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Marked Amelioration of AlcoholResponsive Posthypoxic Myoclonus by ␥-Hydroxybutyric Acid (Xyrem) Steven J. Frucht, MD,1* Yvette Bordelon, MD, PhD,1 and William H. Houghton, MD2 1
Department of Neurology, Columbia University Medical Center, New York, New York, USA 2 Orphan Medical, Inc., Minnetonka, Minnesota, USA
Abstract: We conducted an open-label, dose-finding, blindedrating trial of ␥-hydroxybutyric acid (Xyrem) in a single patient with severe alcohol-responsive posthypoxic myoclonus refractory to treatment with standard antimyoclonic agents. Xyrem was given in divided doses during the day and was well tolerated. Intensity of myoclonus was measured using the Unified Myoclonus Rating Scale, and blinded videotape review demonstrated complete resolution of myoclonus at rest and stimulus-sensitive myoclonus. Action myoclonus and functional performance also improved in ways that were practically meaningful, allowing her to feed herself, to accomplish daily hygiene tasks, and to walk with assistance. The possible mechanisms of action and potential uses of this agent in other alcohol-responsive movement disorders are discussed. © 2005 Movement Disorder Society Key words: myoclonus; hypoxia; gamma-hydroxybutyric acid; Xyrem; rating scale
Posthypoxic myoclonus is an often-devastating neurologic disorder that may follow cardiac or respiratory arrest. Attempts to perform manual tasks or to walk typically trigger intractable action and intention myoclonus. Negative myoclonic jerks often affect muscles of postural support, producing a characteristic bouncing gait, which may render a patient wheelchair-bound.1 Both cortical and subcortical foci may be responsible for generating myoclonic jerks.2 In a recent study using
This article includes Supplementary Video, available online at http:// www.interscience.wiley.com/jpages/0885-3185/suppmat *Correspondence to: Dr. Steven J. Frucht, The Neurological Institute, 710 West 168th Street, New York, NY 10032. E-mail:
[email protected] Received 4 August 2004; Revised 15 November 2004; Accepted 19 November 2004 Published online 4 March 2005 in Wiley InterScience (www. interscience.wiley.com). DOI: 10.1002/mds.20452
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