Bipolar Disorder in Idiopathic Dystonia: Clinical Features and Possible Neurobiology Edward
C. Lauterbach,
M.D.
T. Elisabeth Spears, M.S. Spencer T. Price, B.S.
The authors report 5 patients with bipolar disorders in the context of primary idiopathic dystonia. Four patients had DSM-III-R bipolar disorder, mixed, and one had cyclothymic disorder as diagnosed using the Structured Clinical Interview for DSM-III-R (SCID). All cases of bipolar disorder manifested rapid cycling. Three patients with bipolar disorder experienced onset of this illness soon after the onset of cervicocranial dystonia (5 neck dystonia, 4 craniofacial, 2 brachial, 1 vocal cord,
1 thoracic).
These
cases
apparently
of Neuropsychiatry 1992; 4:435-439)
e found 5 cases of bipolar disorders on examining 28 patients with idiopathic dystonia. We are unable to find previous reports of bipolar disorders in primary idiopathic dystonia, although there have been many reports of depression. We found that the prevalence of bipolar disorders exceeds expectation. We report the diagnostic features of dystonia patients with bipolar disorders, the treatment course of bipolar disorder in one patient, and the clinical, neurobiological, and treatment implications of these findings.
represent
a first report of bipolar disorders in dystonia. Clinical management, relevant literature, and putative neurobiology are reviewed. (The Journal Neurosciences
W
and Clinical
METHODS
Interviews using the Structured Clinical Interview for DSM-ffl-R (SCID) of 28 consecutively encountered patients (blind to the nature of the study) with primary idiopathic dystonia disclosed 5 subjects with bipolar disorders, described below. One additional case of druginduced mania due to trihexyphenidyl is not reported here. Descriptions of these cases and pharmacological management of both disorders (dystonic and bipolar) are reported below. Received October 1, 1992; revised January 31, 1992; accepted April 3, 1992. From the Division of Adult and Geriatric Psychiatry, Department of Psychiatry and Behavioral Sciences, Mercer University School of Medicine, 1550 College Street, Macon, Georgia 31207. Address reprint requests to Dr. Lauterbach at the above address. Copyright © 1992 American Psychiatric Press, Inc.
JOURNAL
OF
NEUROPSYCHIATRY
435
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DISORDER
AND
DYSTONIA
in dystomc
RESULTS
Other symptoms included flight of with grandiosity, impaired concentration, spending sprees, and other behavioral excesses. Major depressive episodes included difficulty concentrating, impaired appetite and insomnia, social withdrawal, decreased libido, anergia, and feelings of worthlessness. Manic and depressive phases would last between several days and a week The patient averaged 4050 cycles per year. Onset was 16 months before examination, approximately 6 months after the apparent onset of the cervical dystonia. This affective disorder was unrelated to ideas,
The prevalence of DSM-ffl-R bipolar disorder (4/28, 14.3%) significantly exceeded the expected prevalence in control subjects in the normal population matched for gender (0.9%, odds ratio = 18.3, P < 1O, Fisher’s Exact Test) and age (0.3%, odds ratio = 56.2, P < 0.005, Fisher’s).12 Individual case descriptions follow.
inflated
neck pain.
self-esteem distractibility,
medication.
CASE
REPORTS 3. A 48-year-old divorced white woman had a 4-year of dystonia of insidious onset, unrelated to any identifiable physical factors other than a minor head and neck injury without lapse of consciousness, which occurred 2 years before onset of dystoma. The dystonia gradually intensified and led to eventual involvement of orbiculares oculi and otis, jaw, tongue, and neck. MRI of the brain 2 years previously was unrevealing. She sustained some degree of improvement on a regimen of trihexyphenidyl 10 mg/d and amitriptyline 75 mg/d, supplemented by either propoxyphene or acetaminophen with codeine q4h pm for dystomc pain control. The DMS was 18/120,1)8 2/30, and BDI 11 (mildly depressed). The patient gave a history of several discrete episodes of irritable mood swings alternating with depressed mood, oscillating disturbance of energy, rapid speech with push of speech when manic, ifight of ideas manifested as racing thoughts, grandiosity, decreased need for sleep when manic, and distractibility when manic or depressed. Onset of this was approximately 18 months after the noticeable onset of dystonia. These shifts in mood would characteristically last only several days, compatible with the rapid-cycling phenomenon of bipolar disorder. The patient experienced more than 4A) cydes each year. During depressive phases the patient would experience depressed mood, insomnia, loss of interest in usual activities and sex, feelings of worthlessness, pathological guilt, suicidal ideation, diminished appetite, and anergia, constituting major depression. This affective disorder was unrelated to medication. Case
Case 1. A 54-year-old married white woman had a 12-year history of dystonia of insidious onset, unrelated to any identifiable physical factors other than a minor head injury without lapse of consciousness occurring about the time of dystoma onset. The dystoma gradually intensified and led to eventual involvement of orbicularis oris, jaw, tongue, left fingers, neck, and muscles of deglutition. CT of the brain 4 years previously was unrevealing. She sustained some degree of improvement on a regimen of trihexyphenidyl 10 mg/d, baclofen 25 mg/d, and donazepam 0.25 mg/d. She had a Dystonia Motor Scale3 (DMS) motor severity rating scale score of 14/120, Disability Scale3 (DS) disabifity score of 6/30, and Beck Depression Inventory4 (BDI) score of 16 (mildly depressed). The patient gave a history of several discrete episodes of irritable mood swings alternating with depressed mood, oscillating energy disturbance, ffight of ideas maidfested as racing thoughts, motor hyperactivity, appetite disturbance, and distractibility beginning several years prior to the noticeable onset of dystonia. These shifts in mood would characteristically last only several days, compatible with the rapid-cycling phenomenon of bipolar disorder. The patient During
was rarely euthymic and major depressive phases
cycled
nearly
continuously.
the patient would experience low mood and feel suicidal, become socially withdrawn, and experience anergia with psychomotor retardation. The affective disorder was unrelated to medication. The patient was treated for the bipolar disorder with lithium carbonate 300mg tid. This led to marked improvement in both the bipolar condition and the dystonia, although she developed a lithium tremor. The tremor was then eliminated with propranolol 30mg tid, and there was further minor improvement in the dystonia. Case 2. A 45-year-old married white woman had a 2-year of dystonia of the neck without identifiable cause. MRI of the head was normal. The dystonia was of gradual onset and progressed to mildly involve the thorax. The patient was maintained on donazepam 3 mg and imiprantine 50mg per day. Her DMS score was 12/120, DS 2/30, BDI 13, with a Hamilton Rating Scale for Depression5 (HRSD) score of 11. The patient had several discrete episodes of irritable and euphoric mood swings, which alternated with depressed mood. Manic episodes consisted of hyperactivity including excessive housework, even though this produced an increase history
436
history
Case 4. A 52-year-old married white woman had a 6-year history of dystonia of the face, vocal cords, neck, and hand without identifiable cause. The dystonia was of gradual onset. CT of the head was normal 1 year after dystoma onset. The patient was maintained on donazepam 1.5 mg and trihexyphenidyl 4mg per day. Her DMS score was 28/120, DS 3/30, BDI 17, and HRSD 11. Manic episodes consisted of elevated mood, inflated self-esteem, flight of ideas, and distractibility lasting 3-4 days, occurring twice a month over the previous 1 year. Prior to the onset of the mania the patient experienced major depressive episodes of at least several weeks, including low mood, difficulty concentrating, insomnia, psychomotor retardation, loss of interest in sex and other activities, anergia, feelings of worthlessness and guilt, and suicidal ideation. Onset of this disorder occurred within 18 months after the development of dystonia and was unrelated to medication.
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LAUTERBACH Case 5. A 62-year-old married white man with an 8-year history of dystonia of the face and neck had a history of multiple concussions, which were of ambiguous relation to the dystoma or the affective disorder. The dystonia was of gradual onset. The patient was maintained on donazepam 2 mg. His DMS score was 14/120 with 1)8 of 4/30. The patient was not depressed at the time of examination, but he was mildly hypomanic. Cyclothymic mood swings consisted of impaired work productivity alternating with periods of heightened productivity with unusual self-imposed work hours, social withdrawal intermixed with increased gregariousness, feeling slowed down alternating with restlessness, hyposexuality alternating with hypersexuality, withdrawal from activities intermixed with periods of overinvolvement in usual activities, and pessimism alternating with overoptimism. Cyclothymic disorder was present for many years before the onset of dystonia.
DISCUSSION The relationship between affective disorders and other movement disorders, including Parkinson’s disease6 and Huntington’s disease,7 has been reviewed elsewhere. Studies of depression occurring in dystonia are reviewed here. Kraft6 described progressive depression, personality changes, and thought disorders in 2 patients with childhood-onset dystonia. Diamond and colleagues9’1#{176}studied 4 patients with blepharospasm (a focal dystonia) and found Minnesota Multiphasic Personality Inventory scores suggestive of depression in 2 patients. Volow1’ reviewed the blepharospasm literature and determined that depressive prevalence varies widely, between 20% and 80%. Many reports do not characterize depression in this literature, often indicating only that depressed mood was present. Jankovic and For&2 studied 100 patients with Meige syndrome (oromandibular dystonia with blepharospasm) and found depression in 25%. Tolosa13 studied 17 patients with Meige syndrome and found 7 (41%) were depressed; depression preceded dystonia onset in 5 cases, 3 had a family history of depression, and 1 developed depression despite good control of the dystonia. Tolosa suggested that common monoamine metabolism abnormalities may explain the association of depression with Meige syndrome. As in Meige syndrome, depression also seems prevalent in cervical dystonia. Jahanshahi and Marsden14 studied 100 torticoffis patients compared with 49 patients who had cervical spondylosis. They determined that 29.4% of patients with cervical dystonia (compared with 15.4% of those who had cervical spondylosis) had moderate to severe depressive ifiness, using a cutoff score of
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et a!.
17 on the Beck Depression Inventory. We’ typified DSMffl-R depressive diagnoses in 24 patients with predominantly focal and segmental cervical dystonia. We found life prevalences of 42% for major depression, 12% for dysthymic disorder, and 12% for bipolar disorders. Depressive disorders bore no relationship to disability, severity of dystonia, or dystomc pain. In contrast, studies of focal upper-limb dystonia have not suggested an increased prevalence of depression in this disorder. Sheehy and Marsden’5 studied 29 patients with the focal hand dystonia “writer’s cramp” using the Present State Examination and found no increased incidence of psychiatric diagnoses in their patients when compared with a normal population. Grafman et al.16 found similar results. Although most of these studies do not allow diagnostic typification, depression of some sort seems associated with cranial and cervical dystonias but not with more distal focal dystonias. There is also some evidence that depression does not relate to psychosocial stressors. The present report is a first description of specific bipolar affective disorders and their treatment in subjects with dystonia. Bipolar disorders with rapid cycling are described. Some of our patients had a history of head injury or another brain insult. This raises an attribution consideration: are the bipolar disorder and the dystonia due to preexistent head injury or brain insult, or is the bipolar disorder secondary to dystonia? Clinically, recognition of bipolar disorders can improve the dystonia patient’s quality of life. Drugs used to treat dystonia affect bipolar disorders. Trihexyphenidyl can worsen bipolar disorder, whereas clonazepam and other benzodiazepines can improve it. Lithium and carbamazepine occasionally improve dystonia. Treatment of bipolar disorder in dystonia patients should commence with lithium, switching to (or adding) carbamazepine if needed. Neuroleptics improve some cases of dystonia but worsen others. In the latter event, neuroleptics should be discontinued, anticholinergics added, or very low potency (strongly anticholinergic) agents could be tried. Benzodiazepines can be employed, since GABA agonists often improve dystonia. Lithium tremor can be treated with beta-blockers, which, although useful for dystonic tremor, rarely affect the primary muscle contractions. This initial report of bipolar disorders associated with dystonia requires confirmation. If it is confirmed, a common neurobiological or genetic substrate is possible. Baxter and others17’9 postulated common striatal substrates and Tolosa13 suggested heritable “neurological neuropathic inferiority” to explain associations between certain movement disorders and psychiatric disorders. If confirmed, our data allow that a striatal disturbance may
437
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DYSTONIA
lead to orbitofrontal and anterior prefrontal cortical dysfunction in bipolar disorders associated with dystonia. Cranial dystonia is associated with affective disorders,”4 whereas more distal focal dystonias are not.’5”6 Cranial motor circuits lie in the ventromedial putamen, whereas distal body circuitry lies more dorsolateraily.2#{176} Although putaminal abnormalities occur in both affective disorders2 and dystonia,4 direct pathological extension to (or motor-modulation oP’) the ventral and ventromedial striatum,27 directly adjacent to the yentromedial putamen, is more likely involved in bipolar disorders.7’’30’3’ Lateralized striatopallidal overactivation, which stimulates bilaterally at the cortex,32 may explain bipolar disorders in dystonia. Mania could result from striatal overactivity of right-lateralized striatopallidothalamocortical and striatonigrothalamocortical pathways via the parvocellular mediodorsal thalamus,32’33 stimulating Brodmann’s area 9 and other dorsolateral prefrontal and neocortical regions,3 thereby overcoming indirect tonic inhibition of these areas by orbitofrontal cortex (Walker’s areas 10_13).32 This is compatible with PET data. 1)2 dopamine receptor blocking agents, disinhibiting striatopallidosubthalamopallidothalamocortical and striatopallidosubthalamonigrothalamocortical pathways,33 would help reverse this condition,u alleviating mania. On the other hand, caudate and thalamic lesions, associated with mania,3 may preferentially disrupt and functionally ablate thalamocortical stimulation of orbitofrontal areas because of the multiple pathways supplying these areas, e.g., limbic, dorsolateral prefrontal, and lateral orbitofrontal. It is thought that the function of orbitofrontal inhibition on the dorsal prefrontal cortex is to screen out extraneous stimuli,32 and this may be why selective cortical lesions of the orbitofrontal cortex produce manic behavior.32 Depression could result from leftlateralizedMu striatopallidothalamocortical stimulation of the orbitofrontal
cortex via the magnocellular32’33 mediodorsal thalamus, which then would inhibit dorsolateral prefrontal and other cortical areas via thalamus and basal ganglia.32 PET data are compatible with cortical inhibition in depression.’ Depressive cognitive, appetitive, and endocrinologic phenomena may be mediated by direct stimulatory dorsal prefrontal32 or inhibitory ventral pallidaP3 pathways to hippocampus and entorhinal cortex, and by direct inhibitory orbitofrontohypothalamic pathways.32 Orbitofrontal and anterior prefrontal cortex dysfunction may be further reinforced by corticocortical association fiber input from other cortical areas, such as the sensory cortex,39 which functions abnormally in dystonia.4#{176} Serotonergic and noradrenergic properties of antidepressants could each remedy depression by acting at striatal interneurons inhibiting striatopaffidal neurons. Dopamine agonists, dopamine reuptake inhibitors, and anticholinergics would stimulate33 the right-lateralized system, producing manic bias, offsetting depression.32 Left anterior frontal lesions associated with depression would ablate dorsolateral prefrontal cortex. In summary, we have presented 5 cases of bipolar disorder in association with idiopathic dystonia. Bipolar prevalence is elevated more than 10-fold. These cases represent a first description of bipolar disorders (and their treatment) occurring in primary dystonia. The data suggest that pathological involvement of the ventromedial striatum may be associated with bipolar disorders. Research questions are raised that remain to be clarified by future investigations.
The authors express their appreciation to Dr. mings, M.D., for his helpful comments on they also thank Norman C. Moore, M.D.,for manuscript and Jean B. Shelley for manuscript port. This work was supported in part by Grant the MedCen Foundation Clinical Research
Cumthis manuscript; comments on the technical sup16-121-50 from Jeffrey
Center,
L.
Macon,
Georgia.
References 1.Lauterbach of
EC, Freeman
affective
disability. 2. Robins
LN,
York, Free
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SE: Huntington’s Disease: A Disorder of Families. BaltiJohns Hopkins University Press, 1989 Kraft IA: A psychiatric study of two patients with dystonia musculorum deformans. South Med J 1966; 59:284-288 Diamond EL, TrobeJD, Belar CD: Psychological aspects of essential blepharospasm. J Nerv Ment Dis 1984; 172:749-756 Trobe JD, Diamond EL, Belar CD: Psychological abnormalities in essential blepharospasm, in Blepharospasm (Advances in Ophthalmic Plastic and Reconstructive Surgeiy, vol 4), edited by BosniakSL, Smith BC. New York, Pergamon, 1985, pp 137-145 Volow MR: Psychiatric aspects of blepharospasm, in Blepharospasm (Advances in Ophthalmic Plastic and Reconstructive Surgery, vol 4), edited by Bosmak SL, Smith BC. New York, Pergamon, 1985, pp 163-174 Jankovic J, Ford J: Blepharospasm and orofacial-cervical dystonia:
7. Folstein
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problems in patients Disord 1989; 4(suppl 12.
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13. Tolosa ES: Clinical features of Meige’s disease (idiopathic orofadal dystoma): a report of 17 cases. Arch Neurol 1981; 38:147-151 14. Jahanshahi M, Marsden CD: Personality in torticollis: a controlled study. Psycho! Med 1988; 18:375-387 15. Sheehy Ml’, Marsden CD: Writers’ cramp-a focal dystonia. Brain 1982; 105:461-480 16. Grafman J, Cohen LG, Hallett M: Is focal hand dystonia associated with psychopathology? Mov Disord 1991; 6:29-35 17. Baxter LR, Schwartz JM, Guze BH, et al: PET imaging in obsessive compulsive disorder with and without depression. J Clin Psychiatry 1991; 51(suppl 4):61-69 18. Kurlan R, Behr J, Medved L, et al: Familial Tourette’s syndrome: report of a large pedigree and potential for linkage analysis. Neurology 1986; 36:772-776 19. Pauls DL, Leckman JF: The inheritance of Gifies de la Tourette’s syndrome and associated behaviors: evidence for autosomal dominant transmission. N Engl J Med 1986; 31 5:993-997 20. Alexander GE, Crutcher MD: Functional architecture of basal ganglia circuits: neural substrates of parallel processing. Trends Neurosa 1990; 13:266-271 21. Husain MM, McDonald WM, Doraiswamy PM, et al: MRI evidence of basal ganglia atrophy in depression (abstract). Paper presented at paper session 25,144th annual meeting of the American Psychiatric Association, New Orleans, LA, May1991 22. Buchsbaum MS. Wu J, De Lisi LE, et a!: Frontal cortex and basal ganglia metabolic rates assessed by positron emission tomography with [‘8F]2-deoxyglucose in affective illness. J Affective Disord 1986; 10:137-152
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32. Fuster JM: The Prefrontal 33. Alexander GE, Crutcher
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23. Chase TN, Tamminga CA, Burrows H: Positron emission tomographic studies of regional cerebral glucose metabolism in idiopathic dystonia, in Dystoma 2, edited by Fahn 5, Marsden CD, Caine DB. New York, Raven, 1988, pp 237-241 (Adv Neurol 50) 24. Lang AE, Garnett ES, Firnau C, et al: Positron emission tomographic studies of regional cerebral glucose metabolism in idiopathic dystonia, in Dystonia 2, edited by Fahn S. Marsden CD, Caine DB. New York, Raven, 1988, pp 249-253 (Adv Neurol 50) 25. Heiligenberg W: The neural basis of behavior: a neuroethological view. Annu Rev Neurosci 1991; 14:247-267 26. Smith AD, Bolam JP: The neural network of the basal ganglia as revealed by the study of synaptic connections of identified neurones. Trends Neurosci 1990; 13:259-265
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SN, Lynd E, Klein C, et al: Topographic organization of the striatal efferent projections in the rhesus monkey: an anterograde tracing study. J Comp Neurol 1990; 293:282-298 Parent A: Extrinsic connections of the basal ganglia. Trends Neurosa 1990; 13:254-258 Alexander GE, DeLong MR. Strick PL: Parallel organization of functionally segregated circuits linking basal ganglia and cortex. Annu Rev Neurosci 1986; 9:357-381 Early TS, Reiman EM, Raichle ME, eta!: Left globus pallidus abnormality in never-medicated patients with schizophrenia. Science 1987; 84:561-563 RapoportJL, Wise SP: Obsessive-compulsive disorder: evidence for basal ganglia dysfunction. Psychopharmacol Bull 1988; 24:380-384
27. Haber
13:402-411
Cortex. New MD, DeLong
York,
Raven,
1989
MR: Basal ganglia-thalamocortical circuits: parallel substrates for motor, oculomotor, “prefrontal” and limbic” functions. Prog Brain Res 1990; 85:119-146 Robinson RG, Starkstein SE: Mood disorders following stroke: new findings and future directions. J Geriatr Psychiatry 1989; 22:1-15 CummingsJL, Mendez MF: Secondary mania with focal cerebrovascularlesions. AmJ Psychiatry 1984; 141:1084-1087 Baxter LR, Phelps ME, Mazziota JC, et a!: Cerebral metabolic rates for glucose in mood disorders. Arch Gen Psychiatry 1985; 42:441447 Schwartz JM, Baxter LR, MazziottaJC, eta!: The differential diagnosis of depression. JAMA 1987; 258:1368-1374 Haskett RE, Mintun MA, Lee KS, eta!: Regional changes in cerebral metabolic rate of glucose during treatment of depression (abstract). Biol Psychiatry 1991; 29(suppl l):83A Mauguiere F, Baleydier C: Place of the thalanius in the network of interconnections monkey. Rev
between
the
association
and
limbic
cortices
in the
Neurol Raichle
(Paris) 1986; 142:406-417 40. PerlmutterJS, ME: Regional cerebral blood flowin dystonia: an exploratory study, in Dystoma 2, edited by Fahn 5, Marsden CD, Caine DB. New York, Raven, 1988, pp 255-264 (Adv Neurol 50) 41. Janowsky 1)9, Risch SD: Role of acetylcholine mechanisms in the affective disorders, in Psychopharmacology: The Third Generation of Progress, edited by Meltzer HY. New York, Raven, 1987, pp 527-533 42. Lauterbach
EC, Schweri
MM: Amelioration
by fluoxetine: possible alteration ology by a selective serotonin pharmacol 1991; 11:392-393
of pseudobulbar
of dopamine-related
uptake
blocker.
affect
pathophysi-
J Clin
Psycho-
439
C. Lauterbach,
M.D.
T. Elisabeth Spears, M.S. Spencer T. Price, B.S.
The authors report 5 patients with bipolar disorders in the context of primary idiopathic dystonia. Four patients had DSM-III-R bipolar disorder, mixed, and one had cyclothymic disorder as diagnosed using the Structured Clinical Interview for DSM-III-R (SCID). All cases of bipolar disorder manifested rapid cycling. Three patients with bipolar disorder experienced onset of this illness soon after the onset of cervicocranial dystonia (5 neck dystonia, 4 craniofacial, 2 brachial, 1 vocal cord,
1 thoracic).
These
cases
apparently
of Neuropsychiatry 1992; 4:435-439)
e found 5 cases of bipolar disorders on examining 28 patients with idiopathic dystonia. We are unable to find previous reports of bipolar disorders in primary idiopathic dystonia, although there have been many reports of depression. We found that the prevalence of bipolar disorders exceeds expectation. We report the diagnostic features of dystonia patients with bipolar disorders, the treatment course of bipolar disorder in one patient, and the clinical, neurobiological, and treatment implications of these findings.
represent
a first report of bipolar disorders in dystonia. Clinical management, relevant literature, and putative neurobiology are reviewed. (The Journal Neurosciences
W
and Clinical
METHODS
Interviews using the Structured Clinical Interview for DSM-ffl-R (SCID) of 28 consecutively encountered patients (blind to the nature of the study) with primary idiopathic dystonia disclosed 5 subjects with bipolar disorders, described below. One additional case of druginduced mania due to trihexyphenidyl is not reported here. Descriptions of these cases and pharmacological management of both disorders (dystonic and bipolar) are reported below. Received October 1, 1992; revised January 31, 1992; accepted April 3, 1992. From the Division of Adult and Geriatric Psychiatry, Department of Psychiatry and Behavioral Sciences, Mercer University School of Medicine, 1550 College Street, Macon, Georgia 31207. Address reprint requests to Dr. Lauterbach at the above address. Copyright © 1992 American Psychiatric Press, Inc.
JOURNAL
OF
NEUROPSYCHIATRY
435
BIPOLAR
DISORDER
AND
DYSTONIA
in dystomc
RESULTS
Other symptoms included flight of with grandiosity, impaired concentration, spending sprees, and other behavioral excesses. Major depressive episodes included difficulty concentrating, impaired appetite and insomnia, social withdrawal, decreased libido, anergia, and feelings of worthlessness. Manic and depressive phases would last between several days and a week The patient averaged 4050 cycles per year. Onset was 16 months before examination, approximately 6 months after the apparent onset of the cervical dystonia. This affective disorder was unrelated to ideas,
The prevalence of DSM-ffl-R bipolar disorder (4/28, 14.3%) significantly exceeded the expected prevalence in control subjects in the normal population matched for gender (0.9%, odds ratio = 18.3, P < 1O, Fisher’s Exact Test) and age (0.3%, odds ratio = 56.2, P < 0.005, Fisher’s).12 Individual case descriptions follow.
inflated
neck pain.
self-esteem distractibility,
medication.
CASE
REPORTS 3. A 48-year-old divorced white woman had a 4-year of dystonia of insidious onset, unrelated to any identifiable physical factors other than a minor head and neck injury without lapse of consciousness, which occurred 2 years before onset of dystoma. The dystonia gradually intensified and led to eventual involvement of orbiculares oculi and otis, jaw, tongue, and neck. MRI of the brain 2 years previously was unrevealing. She sustained some degree of improvement on a regimen of trihexyphenidyl 10 mg/d and amitriptyline 75 mg/d, supplemented by either propoxyphene or acetaminophen with codeine q4h pm for dystomc pain control. The DMS was 18/120,1)8 2/30, and BDI 11 (mildly depressed). The patient gave a history of several discrete episodes of irritable mood swings alternating with depressed mood, oscillating disturbance of energy, rapid speech with push of speech when manic, ifight of ideas manifested as racing thoughts, grandiosity, decreased need for sleep when manic, and distractibility when manic or depressed. Onset of this was approximately 18 months after the noticeable onset of dystonia. These shifts in mood would characteristically last only several days, compatible with the rapid-cycling phenomenon of bipolar disorder. The patient experienced more than 4A) cydes each year. During depressive phases the patient would experience depressed mood, insomnia, loss of interest in usual activities and sex, feelings of worthlessness, pathological guilt, suicidal ideation, diminished appetite, and anergia, constituting major depression. This affective disorder was unrelated to medication. Case
Case 1. A 54-year-old married white woman had a 12-year history of dystonia of insidious onset, unrelated to any identifiable physical factors other than a minor head injury without lapse of consciousness occurring about the time of dystoma onset. The dystoma gradually intensified and led to eventual involvement of orbicularis oris, jaw, tongue, left fingers, neck, and muscles of deglutition. CT of the brain 4 years previously was unrevealing. She sustained some degree of improvement on a regimen of trihexyphenidyl 10 mg/d, baclofen 25 mg/d, and donazepam 0.25 mg/d. She had a Dystonia Motor Scale3 (DMS) motor severity rating scale score of 14/120, Disability Scale3 (DS) disabifity score of 6/30, and Beck Depression Inventory4 (BDI) score of 16 (mildly depressed). The patient gave a history of several discrete episodes of irritable mood swings alternating with depressed mood, oscillating energy disturbance, ffight of ideas maidfested as racing thoughts, motor hyperactivity, appetite disturbance, and distractibility beginning several years prior to the noticeable onset of dystonia. These shifts in mood would characteristically last only several days, compatible with the rapid-cycling phenomenon of bipolar disorder. The patient During
was rarely euthymic and major depressive phases
cycled
nearly
continuously.
the patient would experience low mood and feel suicidal, become socially withdrawn, and experience anergia with psychomotor retardation. The affective disorder was unrelated to medication. The patient was treated for the bipolar disorder with lithium carbonate 300mg tid. This led to marked improvement in both the bipolar condition and the dystonia, although she developed a lithium tremor. The tremor was then eliminated with propranolol 30mg tid, and there was further minor improvement in the dystonia. Case 2. A 45-year-old married white woman had a 2-year of dystonia of the neck without identifiable cause. MRI of the head was normal. The dystonia was of gradual onset and progressed to mildly involve the thorax. The patient was maintained on donazepam 3 mg and imiprantine 50mg per day. Her DMS score was 12/120, DS 2/30, BDI 13, with a Hamilton Rating Scale for Depression5 (HRSD) score of 11. The patient had several discrete episodes of irritable and euphoric mood swings, which alternated with depressed mood. Manic episodes consisted of hyperactivity including excessive housework, even though this produced an increase history
436
history
Case 4. A 52-year-old married white woman had a 6-year history of dystonia of the face, vocal cords, neck, and hand without identifiable cause. The dystonia was of gradual onset. CT of the head was normal 1 year after dystoma onset. The patient was maintained on donazepam 1.5 mg and trihexyphenidyl 4mg per day. Her DMS score was 28/120, DS 3/30, BDI 17, and HRSD 11. Manic episodes consisted of elevated mood, inflated self-esteem, flight of ideas, and distractibility lasting 3-4 days, occurring twice a month over the previous 1 year. Prior to the onset of the mania the patient experienced major depressive episodes of at least several weeks, including low mood, difficulty concentrating, insomnia, psychomotor retardation, loss of interest in sex and other activities, anergia, feelings of worthlessness and guilt, and suicidal ideation. Onset of this disorder occurred within 18 months after the development of dystonia and was unrelated to medication.
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LAUTERBACH Case 5. A 62-year-old married white man with an 8-year history of dystonia of the face and neck had a history of multiple concussions, which were of ambiguous relation to the dystoma or the affective disorder. The dystonia was of gradual onset. The patient was maintained on donazepam 2 mg. His DMS score was 14/120 with 1)8 of 4/30. The patient was not depressed at the time of examination, but he was mildly hypomanic. Cyclothymic mood swings consisted of impaired work productivity alternating with periods of heightened productivity with unusual self-imposed work hours, social withdrawal intermixed with increased gregariousness, feeling slowed down alternating with restlessness, hyposexuality alternating with hypersexuality, withdrawal from activities intermixed with periods of overinvolvement in usual activities, and pessimism alternating with overoptimism. Cyclothymic disorder was present for many years before the onset of dystonia.
DISCUSSION The relationship between affective disorders and other movement disorders, including Parkinson’s disease6 and Huntington’s disease,7 has been reviewed elsewhere. Studies of depression occurring in dystonia are reviewed here. Kraft6 described progressive depression, personality changes, and thought disorders in 2 patients with childhood-onset dystonia. Diamond and colleagues9’1#{176}studied 4 patients with blepharospasm (a focal dystonia) and found Minnesota Multiphasic Personality Inventory scores suggestive of depression in 2 patients. Volow1’ reviewed the blepharospasm literature and determined that depressive prevalence varies widely, between 20% and 80%. Many reports do not characterize depression in this literature, often indicating only that depressed mood was present. Jankovic and For&2 studied 100 patients with Meige syndrome (oromandibular dystonia with blepharospasm) and found depression in 25%. Tolosa13 studied 17 patients with Meige syndrome and found 7 (41%) were depressed; depression preceded dystonia onset in 5 cases, 3 had a family history of depression, and 1 developed depression despite good control of the dystonia. Tolosa suggested that common monoamine metabolism abnormalities may explain the association of depression with Meige syndrome. As in Meige syndrome, depression also seems prevalent in cervical dystonia. Jahanshahi and Marsden14 studied 100 torticoffis patients compared with 49 patients who had cervical spondylosis. They determined that 29.4% of patients with cervical dystonia (compared with 15.4% of those who had cervical spondylosis) had moderate to severe depressive ifiness, using a cutoff score of
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17 on the Beck Depression Inventory. We’ typified DSMffl-R depressive diagnoses in 24 patients with predominantly focal and segmental cervical dystonia. We found life prevalences of 42% for major depression, 12% for dysthymic disorder, and 12% for bipolar disorders. Depressive disorders bore no relationship to disability, severity of dystonia, or dystomc pain. In contrast, studies of focal upper-limb dystonia have not suggested an increased prevalence of depression in this disorder. Sheehy and Marsden’5 studied 29 patients with the focal hand dystonia “writer’s cramp” using the Present State Examination and found no increased incidence of psychiatric diagnoses in their patients when compared with a normal population. Grafman et al.16 found similar results. Although most of these studies do not allow diagnostic typification, depression of some sort seems associated with cranial and cervical dystonias but not with more distal focal dystonias. There is also some evidence that depression does not relate to psychosocial stressors. The present report is a first description of specific bipolar affective disorders and their treatment in subjects with dystonia. Bipolar disorders with rapid cycling are described. Some of our patients had a history of head injury or another brain insult. This raises an attribution consideration: are the bipolar disorder and the dystonia due to preexistent head injury or brain insult, or is the bipolar disorder secondary to dystonia? Clinically, recognition of bipolar disorders can improve the dystonia patient’s quality of life. Drugs used to treat dystonia affect bipolar disorders. Trihexyphenidyl can worsen bipolar disorder, whereas clonazepam and other benzodiazepines can improve it. Lithium and carbamazepine occasionally improve dystonia. Treatment of bipolar disorder in dystonia patients should commence with lithium, switching to (or adding) carbamazepine if needed. Neuroleptics improve some cases of dystonia but worsen others. In the latter event, neuroleptics should be discontinued, anticholinergics added, or very low potency (strongly anticholinergic) agents could be tried. Benzodiazepines can be employed, since GABA agonists often improve dystonia. Lithium tremor can be treated with beta-blockers, which, although useful for dystonic tremor, rarely affect the primary muscle contractions. This initial report of bipolar disorders associated with dystonia requires confirmation. If it is confirmed, a common neurobiological or genetic substrate is possible. Baxter and others17’9 postulated common striatal substrates and Tolosa13 suggested heritable “neurological neuropathic inferiority” to explain associations between certain movement disorders and psychiatric disorders. If confirmed, our data allow that a striatal disturbance may
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lead to orbitofrontal and anterior prefrontal cortical dysfunction in bipolar disorders associated with dystonia. Cranial dystonia is associated with affective disorders,”4 whereas more distal focal dystonias are not.’5”6 Cranial motor circuits lie in the ventromedial putamen, whereas distal body circuitry lies more dorsolateraily.2#{176} Although putaminal abnormalities occur in both affective disorders2 and dystonia,4 direct pathological extension to (or motor-modulation oP’) the ventral and ventromedial striatum,27 directly adjacent to the yentromedial putamen, is more likely involved in bipolar disorders.7’’30’3’ Lateralized striatopallidal overactivation, which stimulates bilaterally at the cortex,32 may explain bipolar disorders in dystonia. Mania could result from striatal overactivity of right-lateralized striatopallidothalamocortical and striatonigrothalamocortical pathways via the parvocellular mediodorsal thalamus,32’33 stimulating Brodmann’s area 9 and other dorsolateral prefrontal and neocortical regions,3 thereby overcoming indirect tonic inhibition of these areas by orbitofrontal cortex (Walker’s areas 10_13).32 This is compatible with PET data. 1)2 dopamine receptor blocking agents, disinhibiting striatopallidosubthalamopallidothalamocortical and striatopallidosubthalamonigrothalamocortical pathways,33 would help reverse this condition,u alleviating mania. On the other hand, caudate and thalamic lesions, associated with mania,3 may preferentially disrupt and functionally ablate thalamocortical stimulation of orbitofrontal areas because of the multiple pathways supplying these areas, e.g., limbic, dorsolateral prefrontal, and lateral orbitofrontal. It is thought that the function of orbitofrontal inhibition on the dorsal prefrontal cortex is to screen out extraneous stimuli,32 and this may be why selective cortical lesions of the orbitofrontal cortex produce manic behavior.32 Depression could result from leftlateralizedMu striatopallidothalamocortical stimulation of the orbitofrontal
cortex via the magnocellular32’33 mediodorsal thalamus, which then would inhibit dorsolateral prefrontal and other cortical areas via thalamus and basal ganglia.32 PET data are compatible with cortical inhibition in depression.’ Depressive cognitive, appetitive, and endocrinologic phenomena may be mediated by direct stimulatory dorsal prefrontal32 or inhibitory ventral pallidaP3 pathways to hippocampus and entorhinal cortex, and by direct inhibitory orbitofrontohypothalamic pathways.32 Orbitofrontal and anterior prefrontal cortex dysfunction may be further reinforced by corticocortical association fiber input from other cortical areas, such as the sensory cortex,39 which functions abnormally in dystonia.4#{176} Serotonergic and noradrenergic properties of antidepressants could each remedy depression by acting at striatal interneurons inhibiting striatopaffidal neurons. Dopamine agonists, dopamine reuptake inhibitors, and anticholinergics would stimulate33 the right-lateralized system, producing manic bias, offsetting depression.32 Left anterior frontal lesions associated with depression would ablate dorsolateral prefrontal cortex. In summary, we have presented 5 cases of bipolar disorder in association with idiopathic dystonia. Bipolar prevalence is elevated more than 10-fold. These cases represent a first description of bipolar disorders (and their treatment) occurring in primary dystonia. The data suggest that pathological involvement of the ventromedial striatum may be associated with bipolar disorders. Research questions are raised that remain to be clarified by future investigations.
The authors express their appreciation to Dr. mings, M.D., for his helpful comments on they also thank Norman C. Moore, M.D.,for manuscript and Jean B. Shelley for manuscript port. This work was supported in part by Grant the MedCen Foundation Clinical Research
Cumthis manuscript; comments on the technical sup16-121-50 from Jeffrey
Center,
L.
Macon,
Georgia.
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