32ournal ofNeurology, Neurosurgery, and Psychiatry 1997;62:352-256

Dystonia in progressive supranuclear palsy

C L Barclay, A E Lang

AbstractObjectives-To document the nature, dis-tribution, and frequency of dystonicsymptoms in progressive supranuclearpalsy (PSP).Methods-Charts and videotapes of allclinically diagnosed patients with PSPseen between 1983 and 1993 were reviewedand the occurrence, nature, and distribu-tion of all dystonic symptoms wererecorded.Results-Of 83 identified cases 38 hadsome dystonic features. Twenty (24%)had blepharospasm (one was induced bylevodopa), 22 (27%) had limb dystonia(one was induced by electroconvulsivetherapy and another by levodopa), 14(17%) had axial dystonia in extension, onehad oromandibular dystonia induced bylevodopa, and two had other cranial dys-tonias. Six patients had limb dystonia asan early or presenting feature, sometimesleading to misdiagnosis of cortical-basalganglionic degeneration. All threepatients who had postmortem confirma-tion ofthe diagnosis had other concurrentdisease. One patient with bilateral limbdystonia and blepharospasm had evi-dence of previous hydrocephalus andsevere arteriosclerotic changes. One witharm dystonia also had cerebrovasculardisease and one with hemidystonia alsohad rare swollen chromatolytic neuronsin the frontotemporal cortex.Conclusions-Dystonia is a commonmanifestation of PSP. Limb dystonia isparticularly common and may indicatethe presence of concurrent disease. Whendystonia occurs in PSP, dopaminergicmedication should be cautiously reducedor discontinued to rule out the possibilityoftreatment induced symptoms.

( Neurol Neurosurg Psychiatry 1997;62:352-356)

Keywords: progressive supranuclear palsy; dystonia;parkinsonism

Since progressive supranuclear palsy (PSP)was first characterised in 1964,1 dystonic man-ifestations have been reported only sporadi-cally.2-7 "Axial dystonia in extension" is theonly such manifestation which has beenemphasised; however, the pathogenesis of thistonic, rigid extended posture is probably dis-tinct from other forms of dystonia.Blepharospasm has also been reasonably well

recognised in this setting, whereas limb dysto-nia, oromandibular dystonia, and treatmentinduced dystonia have all but been ignored. Inreviewing a large series of patients with PSP,we were impressed with the frequency of dys-tonia and report our findings below.

MethodsThe charts of all patients with a diagnosis ofPSP who were seen in the Toronto Hospitalmovement disorders clinic between January1983 and February 1993 were reviewed. Allvideotaped examinations available on thesepatients were reviewed. The clinical diagnosiswas considered correct if the patient had aprogressive, non-familial neurodegenerativedisorder with onset after the age of 40 whichincluded supranuclear ophthalmoplegia withdowngaze abnormalities and at least two of thefollowing features: postural instability withbackward falls, pseudobulbar palsy, bradyki-nesia and rigidity, frontal lobe signs, or axialdystonia and rigidity (Lees' criteria).9 Anypatient with limb apraxia, cortical sensory loss,or dysphasia was excluded. All patients satisfy-ing the criteria were reviewed for the presenceof dystonia. This was defined as a syndrome ofinvoluntary movement dominated by sus-tained muscle contractions causing twistingand repetitive movements or abnormal pos-tures.'0 Clinical aspects of the dystonic mani-festations were reviewed including thelocation, nature, accompanying clinical fea-tures, and the time of onset. Accurate infor-mation on the time of onset in relation toonset of disease was not always available.

ResultsEighty three patients met the diagnostic criteriafor PSP; 45 were men and 37 were women(1 2:1). Twenty seven had at least one video-taped examination. The age at onset of PSPsymptomatology ranged from 47 to 81 years ofage with a mean of 62-9 years. Duration ofPSP symptoms to last follow up visit or deathwas 4-7 (range 1-20) years. Thirty eight(46%) had at least one dystonic feature atsome point in their illness. Twenty had ble-pharospasm (24%), 22 had limb dystonia(27%), 14 were noted to have so called axial"dystonia" in extension (17%), and three hadother cranial dystonias. In three patients, thedystonia was clearly induced by treatment(one with oromandibular dystonia and ble-pharospasm and two with limb dystonia).

Blepharospasm occurred either sponta-

University of Ottawa,Division ofNeurology,Ottawa Civic Hospital,1053 Carling Avenue,Ottawa, OntarioK1H 4Y9, CanadaC L BarclayUniversity ofToronto,Toronto Hospital,Western Division, MP1lth Floor, Room 306,399 Bathurst Street,Toronto, OntorioM5T 2S8, CanadaA E LangCorrespondence to:Dr C L Barclay.Received 4 August 1995and in final revised form14 November 1996Accepted 14 November 1996

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neously or reflexively in response to facialstimuli or voluntary facial movements (reflexblepharospasm). Because of incompletereporting, it was not possible to discern howmany patients had isolated spontaneous ble-pharospasm, reflex blepharospasm only, or acombination of the two. Ten of the 20 patientswith blepharospasm also had "apraxia of eye-lid opening" (referred to elsewhere as levatorinhibition or eyelid freezing). Reflex ble-pharospasm was a common accompaniment ofthis disorder. Two patients had ble-pharospasm with apraxia of eyelid closure. Innearly all those affected, blepharospasmoccurred as a late manifestation of their dis-ease, with only one patient reporting difficultywith eyelid opening within one year of onset ofsymptoms. One patient with blepharospasmand other dystonic features had a postmortemperformed and the results are reported below.One patient developed blepharospasm and

oromandibular dystonia while receiving lev-odopa/carbidopa 100/25 thrice daily. On with-drawal of the drugs, the blepharospasmresolved but apraxia of eyelid openingremained. The oromandibular dystonia alsoresolved on stopping levodopa. No otherpatient had oromandibular dystonia althoughone had a dystonic grin with repetitive lowerfacial grimacing and one had sustained invol-untary smiling.Limb involvement was the most common

dystonic manifestation in our PSP population(22 patients, 27%) and hemidystonia the mostfrequent distribution (nine patients (11%)).Although in many instances the precise limbposture was not recorded, a "pointing gun"posture, with extension of the index finger andthumb, was often noted. In four patients,hemidystonia was a very early or presentingfeature of their disease. Two were initiallydiagnosed elsewhere as having cortical-basalganglionic degeneration because of the pro-nounced unilateral (left sided) dystonia.However, these patients had a verticalsupranuclear gaze palsy at presentation and nocortical sensory loss or stimulus sensitivemyoclonus. Significant limb apraxia was alsoabsent but was difficult to assess due to thepronounced disability caused by their dysto-nia, bradykinesia, and rigidity. One patient,last seen six years after symptom onset,remains free of manifestations of cortical-basalganglionic degeneration. The other died fiveyears after onset of symptoms. Postmortemexamination disclosed the typical pathologicalabnormalities of PSP. In addition, rare swollenchromatolytic neurons were noted in the fron-totemporal cortex and there was neuronal lossand gliosis in the left motor cortex and rightposterior middle frontal gyrus. These findings,although suggestive of cortical-basal gan-glionic degeneration, have been described inPSP"I-"3 and due to the overwhelming predom-inance of the findings of this disorder, the finalneuropathological diagnosis was that of "atyp-ical PSP".'4

Single limb involvement occurred in eightpatients (10%). In seven, an arm was involved.In one the patient developed dystonia in his

left leg during a course of electroconvulsivetherapy.'5 Within one month of cessation ofthat treatment, this symptom resolved. Itspontaneously recurred and gradually wors-ened over the subsequent 18 months of followup. One patient developed right arm dystoniawith associated choreic movements whilereceiving levodopa/carbidopa. All involuntarymovements ceased on discontinuation of thedrug.

In two other cases, arm dystonia was theinitial manifestation of disease. One of these,with right arm involvement, died after an eightyear history of gradually progressive neurologi-cal dysfunction compatible with a clinicaldiagnosis of PSP. Postmortem examination, inaddition to the typical pathological changes ofPSP, showed severe arteriosclerosis withmicroinfarcts in the left caudate, left lateralthalamus, right dorsomedial thalamus, andmultiple neocortical regions.The one patient with dystonic posturing in

all four limbs late in the course of his illnessalso had PSP confirmed at necropsy. Thispatient is reported elsewhere.'6 He presentedat age 69 with incontinence, gait impairment,falls, and cognitive dysfunction. Brain CT sug-gested normal pressure hydrocephalus andventricular shunting was performed. Hissymptoms improved greatly for a few months;however, his gait then worsened, dysphagiaand dysarthria occurred, and he developed avertical supranuclear gaze palsy, ble-pharospasm, and mild bilateral limb dystonia.He died aged 75 and in addition to the typicalfindings of PSP, his postmortem examinationshowed evidence of previous hydrocephalusand severe arteriosclerotic changes in thewhite matter and deep grey structures withnumerous small infarcts (1-8 mm in diameter)bilaterally in the centrum semiovale and basalganglia.

Whereas we do not consider the neck pos-ture typically seen in PSP to be dystonic innature, as some authors consider it such, werecorded the frequency of this feature.Fourteen patients (17%) were documented ashaving "axial dystonia in extension". This wascharacterised by constant extensor posturingof the neck with severe nuchal rigidity. Nopatient had phasic or intermittent dystonicneck movements, improvement with antago-nistic gestures, "morning benefit", or otherclinical features characteristic of classic cervi-cal dystonia.With the retrospective nature of this review,

the lack of a consistent approach to treatment,and the complex symptomatology that ourpatients experienced, an accurate assessmentof the response of the patients' dystonia tomedical management could not be obtained.None of the patients receiving levodopa ordopamine agonists were reported to experi-ence a lessening of their dystonic symptoms.Rarely, patients with limb dystonia or ble-pharospasm were noted to have some benefi-cial response to tricyclic agents whereas onlythose who received botulinum toxin injectionsfor blepharospasm clearly experienced a goodresponse to therapy. No patient in this series

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with any other form of dystonia received botu-linum toxin injections.

DiscussionDystonia was first reported in association withPSP with the initial description of the disorderby Steele, Richardson, and Olszewski in1964.1 Whereas they emphasised "axial dysto-nia in extension", one of their patients alsoshowed unilateral arm dystonia.

Axial dystonia in extension is by far themost commonly recognised and reported"dystonic" manifestation of PSP. De Bruinand Lees noted that 48-3% of all necropsiedpatients with PSP reported in the literaturehad axial dystonia of some sort. 17 The posturingseen in this condition, however, lacks the typi-cal features of dystonia and many authorsthink that this term should be avoided.8 18 Theneck positioning in PSP tends to be fixed anddoes not alter with posture or activity as idio-pathic dystonia does. Patients fail to show sen-sory tricks for improving the posturing, diurnalvariation ("morning benefit") is absent, andpainful neck spasms and hypertrophic musclesare not seen. For these reasons, nuchal rigidityin extension would be a more appropriateterm. We would reserve the term "axial dysto-nia" for those rare cases reported in which tor-ticollis was described.1' 20 In our series, nopatient had such neck movements. Fourteen(17%), however, were noted to have overtnuchal rigidity in extension. This is likely anunderrepresentation of the true prevalence ofthis sign as the position of the neck was notalways specified and so milder examples mayhave been overlooked or not documented.The most widely accepted dystonic mani-

festation of PSP is blepharospasm.2' In twoclinic based series, blepharospasm was notedin between 8% and 23% of cases.22 23 Golbe etal reported a community based series of 38patients with PSP in whom 10 (26%) had ble-pharospasm, or "levator inhibition" ("apraxiaof eyelid opening"), or both.24 It should benoted that "levator inhibition" is probably anuncommon cause of "apraxia of eyelid open-ing". Recent studies have emphasised thepresence of isolated contraction of the pre-tarsal component of the orbicularis oculi mus-cle in a high proportion of cases, making this asubtype of dystonic blepharospasm.2326 Golbeet al noted that the duration and severity ofdisease in patients with disturbances of eyelidfunction was not significantly different fromthose lacking this feature although they didnote the presence of more severe upgazeabnormalities.24 In our series, 31 patients(40%) had disturbances of eyelid functionincluding eight with blepharospasm alone, and12 with a combination of blepharospasm andapraxia of eyelid opening or closure. The ret-rospective nature of our series, with insuffi-cient recording of some clinical features, doesnot allow us to confirm the findings of Golbeet al of more severe upgaze impairment inthese patients. However, in our patients, ble-pharospasm tended to be a late manifestationof disease, occurring within one year of onset

of symptoms in only one patient.One patient with blepharospasm in our

series had postmortem confirmation of diag-nosis but he also had severe arterioscleroticchanges and normal pressure hydrocephaluswhich may have contributed to the develop-ment of this symptom. The pathological distri-bution of degenerative changes in classic PSPincludes extensive involvement of the mid-brain and as midbrain lesions have beenknown to result in blepharospasm,27 it is notsurprising that this sign occurs so often inPSP. The more severe abnormalities of eyemovement noted by Golbe et al would also beconsistent with this.24De Bruin and Lees recently reviewed

reports of patients with pathological changesof PSP and found 90 cases.'7 Only five (5 6%)had blepharospasm; however, only 68-5% oftheir cases actually met clinical criteria for adiagnosis of PSP. The patients who did notfulfill the criteria lacked the appropriate eyefindings, suggesting that they had less severepathological involvement of the midbrain, per-haps explaining the low frequency of this sign.In addition, after the initial characterisation ofthe disease, necropsied cases reported in theliterature are more likely to be atypical and sothis series may have underestimated the trueprevalence of this sign in PSP.

Oromandibular dystonia or other cranialdystonias are rare features of PSP. In 1968,David et al described a patient with "dystonicstiffness" of the face28 and Anzil reportedanother with "trismus".29 Although in bothcases, the diagnosis was confirmed at necropsyit is not clear from the case summaries thatthese signs were truly dystonic. A recentnecropsy series of 12 patients with PSPreported one with dystonia of the face30 but thenecropsy series of 90 cases reported by DeBruin and Lees does not comment on this signat all.'7 Details in clinical series are similarlylacking. Jankovic et al reported that 28 of 104patients had blepharospasm "or other facialspasms".22 Elsewhere they noted that 24 ofthese had blepharospasm but there is no men-tion of the nature of the "facial spasms" in theother four or whether any of the patients withblepharospasm had other associated facialmovements. Hayashi et al described a case ofotherwise typical PSP in which the patientdeveloped tonic contraction of the orbicularisoris and palatal muscles when attempting tomake certain sounds.3' Although they consid-ered that this was analogous to apraxia of eyelidopening, it may represent a form of facial dys-tonia.

Whereas one of our patients had a dystonicgrin with intermittent repetitive semirhythmi-cal movements of the muscles of her lowerface and one had sustained involuntary smilingwhich appeared dystonic, many patients hadfacial "stiffness" which was not clearly dys-tonic in nature. In these patients, the facialstiffness was accompanied by a concomitantincrease in facial reflexes and we thereforeconsidered this appearance to be due to spas-ticity rather than dystonia. Although thecharacteristic sustained eyebrow elevation

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commonly seen in PSP may represent dystonicinvolvement of the frontalis muscle, it couldalso represent a variable combination of spas-ticity, rigidity, and a response to difficulty witheyelid opening. In view of the uncertainty ofclassification, we chose, for the purpose of thisreport, not to record the furrowing of the browor the deepening of the nasolabial folds as fea-tures of dystonia.No patient in this series had spontaneous

oromandibular dystonia. One patient withlong standing PSP, however, had jaw closuredystonia and blepharospasm while taking lev-odopa. On discontinuation of this medication,both dystonic symptoms resolved completely.It is important to emphasise that the cause andeffect relation between the dystonic symptomsand levodopa therapy was not readily apparentin this patient until long term levodopa treat-ment was withdrawn. The same is true of theone patient with limb dystonia induced by lev-odopa. Given our experience, the potentialrole of medication, especially levodopa, mustbe considered when dealing with dystonia inpatients with PSP.

Despite a lack of emphasis on this feature inthe literature, we found limb involvement tobe the most frequent type of dystonia in ourseries. When Steele, Richardson, andOlszewski first described this condition in1964, they reported seven necropsied casesand two clinical cases. One of the necropsiedcases had "athetoid posturing of the limbs"'and one of the clinical cases, which subse-quently came to necropsy, developed a "hemi-plegic dystonic posture".32

Very little emphasis has been placed on thisfeature since then. Jankovic et al reported theonly large clinical series in which limb dystoniawas not a rare or absent sign.22 They described"hand or foot deformity" that was elsewherecalled dystonia, in 14% of a series of 104patients. Unfortunately no further details weregiven regarding these patients. Similarly, DeBruin and Lees reported that 18 of 90 patientswith PSP had "segmental dystonia" onnecropsy but no further details were providedhere either.'7 It is not clear if all of thesepatients had limb dystonia or if some hadcraniocervical dystonia. The same difficultyexists with the series of 21 necropsied casesreported by Veiny et al.33 Two of these patientswith typical pathologically established PSPwere reported to have "focal or segmental dys-tonia". A review of the text suggests that theywere referring to limb dystonia, but this wasnever clarified. Leger et al described two oth-erwise typical clinical cases of PSP with iso-lated upper limb dystonia as a presentingfeature34 and Rafal and Friedman describedthe presence of limb dystonia in eight of 30patients (27%) with clinically diagnosedPSP.35 In the last series, the dystonia occurredbefore the onset of the typical abnormalities ofeye movement in half of the patients. In ourlarger series, we noted limb dystonia in a simi-lar proportion with 22 of 83 patients beingaffected. This was a presenting feature in asmall proportion (6/22 or 27%).

All of our patients with limb dystonia who

went on to postmortem examination showedother concurrent diseases (two had cere-brovascular disease and one had additionalcortical findings). It is possible that limb dys-tonia in PSP is an indicator of concomitantneuropathological changes, but it must beemphasised that a necropsy was more activelysought in those patients who had atypicalclinical features. The pathological findingsdescribed in our three patients undergoingpostmortem examination, therefore, may notbe representative of the entire subgroup ofpatients with limb dystonia. However, it isbecoming increasingly recognised that corticalpathology such as described in one of thesepatients does occur in PSP.11-13 36 Thesechanges may not necessarily imply the pres-ence of a concurrent second disease but mightsimply represent part of the range of the dis-ease. A recent clinicopathological conferencein the New England Journal of Medicine,37 anecropsied case of PSP with arm dystoniadescribed in the French literature,38 andSteele's experience32 clearly show that limbdystonia can be prominent in pathologicallyestablished typical PSP without any otherassociated disease. Our experience and thatdescribed in the New England Journal ofMedicine37 emphasise the potential for thepresence of focal limb dystonia to encourage amisdiagnosis of cortical-basal ganglionicdegeneration. Caution then must be exercisedin diagnosing ideomotor apraxia in the pres-ence of severe dystonic posturing, rigidity, andbradykinesia.

Although referral bias in this series mayhave resulted in the accrual of a higher propor-tion of atypical cases and, consequently, anoverestimate of the frequency of dystonia inPSP, our findings clearly indicate that dystoniais a common manifestation of PSP. Limb dys-tonia, although sometimes indicative of otherconcurrent pathology, may be the presentingsymptom of this disorder. Recognition of thismay avoid misdiagnosis of cortical-basal gan-glionic degeneration or some other condition.Our series also shows the potential for

dopaminergic medication to induce dystoniain PSP. Although this may be an infrequentcause, when dystonia is noted in patients onsuch medications, the dosage should be cau-tiously reduced or eliminated in an attempt toestablish the role of drug therapy in the causa-tion of this disabling complication.

Further study of community based popula-tions with associated clinical-pathological cor-relation is necessary if the true frequency andanatomical substrates of the dystonic manifes-tations of this disorder are to be clarified.

We are indebted to Dr C Bergeron for the careful neuropatho-logical assessment of the cases described.

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