J Neurol (2001) 248 : 1106–1108© Steinkopff Verlag 2001

Shinji Ohara

Dressing and construc-tional apraxia in a patientwith dentato-rubro-pallido-luysian atrophy

Received: 16 April 2001Received in revised form: 21 June 2001Accepted: 28 June 2001

Sirs: Dentato-rubro-pallidoluysian atrophy (DRPLA) is an au-tosomal dominant multisystemneurodegenerative disease, mostcommonly found in Japan, that isclinically characterized by chorea,cerebellar ataxia, and dementia aswell as progressive deterioration[1, 2]. The genetic defect ofDRPLA is a cytosine-adenine-guanine (CAG) triplet nucleotideexpansion of the atrophin-1 geneon chromosome 12. The dementiaseen in DRPLA is typically subcor-tical without focal cognitive im-pairments such as aphasia, apraxia,and agnosia [3]. We describe here apatient with DRPLA who presentedwith constructional apraxia andcortical sensory deficits and im-proved after the administration ofneuroleptics.

A 50-year-old man was broughtto our clinic by his wife with thechief complaint of difficulty in car-rying out daily routines. He had re-tired from his job as a laboratoryworker 6 months earlier because ofa decline in his performance. Hehad a positive family history ofdentato-rubro-pallido-luysian atro-phy (DRPLA), his mother and histwo sons having been affected. Histwo sons both had seizure disor-ders and mental retardation andhad been diagnosed with DRPLAupon genetic analysis.

The patient had difficulty inmanipulating learned objects such

as the phone or a semi-automatedtoilet. He could not use a touch-phone anymore because he con-fused the numbers on the keypad,although he had correct verbal re-call of the numbers. When usingthe toilet, he would push the wrongbutton to flush the water. He wouldalso light the wrong end of a ciga-rette. Dressing by himself had be-come particularly difficult as hewould insert an arm in the neckaperture or try to fit both legs inone leg of the trousers. It was as ifhe could not distinguish parts ofthe clothing or could not remem-ber how to dress.

On examination, he was some-what irritable. His speech wasslightly explosive and uninhibited,and the content of his speech wasoften incoherent and slightly delu-sional, but without deficits in artic-ulation and fluency. His languagewas normal. He could follow 3-stepcommands across the midline. Hewas fully oriented and was able toremember 3 out of 3 items after 5minutes. His long-term memorywas well preserved. Smooth-pur-suit eye movement was slightlyjerky; otherwise, the rest of the cra-nial nerve examination was nor-mal. When speaking, his headshowed a slight rotational tremor.His muscle strength and bulk werenormal. Finger nose-to-finger test-ing was accurate but was inter-rupted by some choreic movement.He was astereognosic despite nor-mal sensations to light touch, pin-prick, and vibration on both hands.For example, he was able to de-scribe the tactile features of aneraser (soft, light), but could notrecognize it. The sense of graphes-thesia was mildly decreased overhis palm. There was no finger ag-nosia, right-left disorientation,dyscalculia, or tactile or visual ne-glect. His color perception was nor-mal. He performed poorly on testsof spatial construction, such asdrawing a clock or copying a cube

(Fig. A, C). He was unable to imitatespecific finger postures. He wasable to pantomime how to blow amatch, salute militarily, smoke acigarette, and kick a ball. However,he rubbed his thumb on his teethwhen pantomiming how to brushthe teeth and pounded his fist onthe table while showing how tohammer a nail. His praxis im-proved with real tools. His gait waswide-based and unsteady. His deeptendon reflex was diffusely hyper-active, and planter reflexes were inflexion bilaterally. He did not sufferfrom urinary incontinence or or-thostatic hypotension.

Routine hematological andchemical laboratory results werenormal. Upon genetic analysis, aCAG repeat expansion was con-firmed. Brain MRI showed slightcerebral and cerebellar atrophy.Single Photon Emission ComputedTomography (SPECT) with N-iso-propyl-p [I-123]-iodoamphetaminerevealed hypoperfusion of the pari-etal areas. Motor and sensorynerve-conduction studies werewithin normal range. Electroen-cephalogram and auditory-evokedresponses were normal, while so-matosensory-evoked potentials af-ter stimulation of the mediannerves at the wrist revealed normalN20 latency on both sides.

The patient was started onhaloperidol 0.75 mg twice a day,which was then increased to threetimes a day after a month. Twomonths later, he was once againable to use a touch-phone withoutmuch difficulty. He was also able todress by himself without assis-tance. His wife thought that hisprevious level of activity had al-most returned. On examination, hewas cooperative and spoke sensi-bly. His choreic movement and ro-tatory head jerks were improved,and his gait was less ataxic.

At this time, he was tested withthe revised Wechsler Adult Intelli-gence Scale (WAIS-R). His verbal

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IQ was 119, while his performanceIQ was only 63. He scored 15 out of61 in a block-design test, and 14out of 47 in a picture-combinationtest. He scored 35/36 in the RavenMatrix, and his drawing of a cubicwas improved (Fig. D). Four monthslater, his daily living activities re-mained improved. Upon examina-tion, his drawings were further im-proved (Fig. B, E). Still, he could notrecognize small objects by touch.He was able to imitate hand pos-ture more easily, but he had stillproblems in imitating how to brushhis teeth, or to hammer a nail. Atthe 6-month follow-up visit, hisneurological findings remained un-

changed and the repeated SPECTstudy did not show significant in-terval changes.

The clinical presentation ofhereditary DRPLA is quite diverse,depending on the age of onset. Inpatients with adult onset, cerebellarataxia or choreoathetoid move-ments tend to dominate the clinicalpicture, whereas in patients withjuvenile onset, seizures and my-oclonus are more common. A pro-gressive intellectual impairmentand/or personality changes are alsocommonly observed in the adult-onset form, and those often pre-cede the appearance of motor man-ifestation. The dementia in DRPLA

is “subcortical”, primarily consist-ing of psychomotor slowing with-out cortical dysfunction such asaphasia or apraxia. Our case pre-sented with bilateral astereognosia,dressing and constructionalapraxia, and less prominently ideo-motor apraxia. All of these corticaldeficits occurred in the context ofnormal memory, abstractions, andlanguage comprehension. To ourknowledge, this presentation hasnot been reported in a case ofadult-onset DRPLA.

The site of cortical dysfunctioncan be localized to the parietal cor-tex based on the clinical presenta-tion. It is generally accepted thatthe parietal lobes are the principalcortical areas involved in visual-motor integration responsible forconstructional ability [4]. Dressingapraxia is rarely reported in combi-nation with constructional distur-bance. However, Yamaguchi et al.have reported a 60-year-old Japan-ese man with possible corticobasaldegeneration who presented with a2-year history of slowly progressivedressing apraxia and construc-tional apraxia without otherapraxia or aphasia [5]. They postu-lated a common underlying distur-bance in visual-spatial recognitionto explain this association. Recentevidence indicates that astereo-gnosia is related to a focal lesion inthe contralateral parietal cortex,which receives direct input fromthe finger joints [6].

Previous neuropathologicalstudies of DRPLA brains have con-sistently revealed predominantsubcortical foci of degeneration,whereas the anatomical correlatesof the progressive dementia in DR-PLA have not been fully clarified[7]. It is possible that the anatomi-cal damage is predominantly sub-cortical, causing parietal symptomsvia known basal-thalamo-corticalconnections. Potentially similarcortical deficits and metabolic ab-normalities after the appearance ofsubcortical lesions have both beendescribed in other neurodegenera-

Fig. A, B Drawing of a clock by the patient. A) Before starting on neuroleptics. The patient was asked to putnumbers and arms on the circle drawn. B) 4 months later. The patient was asked to draw a clock showing a timeof 2:30. C, D, E Copy of a cubic figure by the patient. C) Before starting neuroleptics. D) 2 months later. E) 4 monthslater. The sample presented at the time of each drawing is shown above. Original x 0.5

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5. Yamaguchi H, Kawamura M, YokochiM, Yano Y (1998) Slowly progressivedressing and constructional apraxia:symptomatological study, especiallyfor dressing apraxia. Clin Neurol38:897–903 (in Japanese, English ab-stract)

6. Tomberg C, Desmedt JE (1999) Failureto recognize objects by active touch(astereognosia) results from lesion ofparietal cortex representation of fingerkinaesthesis. Lancet 534:393–394

7. Takahashi H, Ohama E, Naito H,Takeda S, Nakashima S, Makifuchi T,Ikuta F (1988) Hereditary denta-torubral-pallido-luysian atrophy: Clin-ical and pathologic variants in a fam-ily. Neurology 38:1065–1070

8. Perani D, Di Piero V, Lucignani G, Gi-lardi MC, Pantano P, Rosetti C, PozzilliC, Gerundini P, Facio F, Lenzil GL(1988) Remote effects of subcorticalcerebrovascular lesions: a SPECT cere-bral perfusion study. J Cereb BloodFlow Metab 8:5607

9. Yamada M, Wood JD, Shimohata T,Hayashi S, Tsuji S, Ross CA, TakahashiH (2001) Widespread occurrence of in-tranuclear atrophin–1 accumulation inthe central nervous system neurons ofpatients with dentatorubral-palli-doluysian atrophy. Ann Neurol49:14–23

Dr. S. Ohara, MD (�)Department of NeurologyNational Chushin-Matsumoto Hospital811 KotobukiMatsumoto 399–0021, JapanFax: +81-2 63/86-31 90

tive diseases such as Alzheimer’sdisease and in stroke [8]. It is pos-sible that the subcortical pathologi-cal changes of DRPLA may affectrelevant cortical functions throughtheir connections. Recently, how-ever, it has been shown that a dif-fuse accumulation of mutant at-rophin–1 in the neuronal nuclei isthe predominant pathological con-dition of the DRPLA brain and in-volves a wide range of CNS regionsfar beyond the combined degener-ation of the dentatorubral andpallidoluysian systems [9]. In thatstudy, the cerebral cortex wasamong the sites preferentially af-fected, suggesting the primary roleof cortical pathology in producinga variety of clincal features of DR-PLA, including dementia andepilepsy. Since the clinical improve-ments in our patient included bothautomatic and non-automatic tasksrequiring more attention and con-centration, it seems unlikely thathis visuospatial deficit was simplydue to his chorea/or psychiatric ill-ness.

The medical treatment of DR-PLA is limited. It is usually directedto the symptomatic improvementof movement and emotionaldeficits with neuroleptics and/oranti-depressants. In our case, theresponse to treatment with theneuroleptics was quite remarkable,since not only chorea but also visu-

ospatial abilities were improved. Itremains unclear at present whetherthese deficits were related tochorea, with difficulty with sequen-tial motor programs, which haswell disappeared with the treat-ment, or can such a deficit be re-versible with this type of drug. Fur-ther case studies of DRPLA seemwarranted, with special attentionbeing paid to visuospatial functionand its response to treatment withneuroleptics.

■ Acknowledgments We thank Dr.KunihiroYoshida, Department of Medicine (Neurol-ogy), Shinshu University School of Medi-cine, for conducting the genetic analysis,andDr. Maurizio Corbetta, Department of Neu-rology, Washington University School ofMedicine, for his invaluable discussion andcritical reading of the manuscript.

References

1. Kanazawa I (1998) Dentatorubral-pal-lidoluysian atrophy or Naito-Oyanagidisease. Neurogenetics 2:1–17

2. Tsuji S (1999) Dentatorubral-pallido-luysian atrophy (DRPLA): Clinicalfeatures and molecular genetics. InAdvance in Neurology. Vol. 79, eds. AVDelgado-Escueta, WA Wilson, RWOlsen and RJ Porter. 399–409

3. Naito A (1995) Clinical picture ofDRPLA. No to Shinkei 47:931–938. (InJapanese)

4. Benton A, Tranel D (1993) Visuoper-ceptual, visuospatial, and visuocon-structive disorders. In Clinical neu-ropsychology. 3rd ed. Oxford Univ.Press 165–213