J7ournal ofNeurology, Neurosurgery, and Psychiatry 1993;56:1323-1326

SHORT REPORT

Primitive reflexes in Parkinson's disease

FredW Vreeling, Frans R J Verhey, Peter J Houx, Jellemer Jolles

AbstractA standardised protocol for the exami-nation of 15 primitive reflexes in whichthe amplitude and the persistence werescored separately, was applied to 25patients with Parkinson's disease and anequal number ofhealthy matched controlsubjects. Most reflexes were found con-siderably more often in the patients thanin the control subjects, especially thesnout, the glabellar tap, and its variant,the nasopalpebral reflex. Only the mouthopen finger spread reflex was presentmore often in the control subjects. Forall reflexes except this last, the scores foramplitude and persistence of the reflexesfor the control group never exceeded thescores for the patient group. Reflexespersisted more often in the patients thanin the control subjects. Parkinsonismalone can explain a large number ofprimitive reflexes, irrespective of theseverity or duration of the disease. Incontrast, the number of reflexes wasrelated more closely to cognitive scales.It is concluded that such reflexes may behelpful in diagnosing Parkinson's dis-ease. In addition, a standardised protocolfor eliciting and scoring is essential forthe study of these reflexes in parkin-sonism and other neuropsychiatricconditions.

(7 Neurol Neurosurg Psychiatry 1993;56:1323-1326)

University ofLimburg,Maastricht, TheNetherlandsDepartment ofNeurologyFW VreelingDepartment ofNeuropsychology andPsychobiologyF R J VerheyP J HouxJ JollesCorrespondence to:Dr FW Vreeling,Deparanent of Neurology,University of Limburg,PO Box 616, 6200 MDMaastricht, TheNetherlands.Received 11 September 1992and in revised form11 February 1993.Accepted 24 February 1993

The prevalence and clinical value of primitivereflexes in Parkinson's disease have been dis-cussed by many authors."A Although some ofthese reflexes can be elicited in normal adults5and in patients with focal lesions,6 they arefound more often in patients with diffuse,hemispherical disease.7-'0The glabellar tap,23" 12 the snout,'210 and

palmomental'24 '3 reflexes are especially fre-quently found in Parkinson's disease. Theproportion of glabellar tap, snout, nasopalpe-bral, suck, and grasp reflexes increases withthe severity of the disease.38 Findings for thepalmomental reflex are controversial.2 Thepresence of primitive reflexes increases withcognitive impairment.2810 No relationship hasbeen found between the reflexes and theduration of the disease or the degree ofdepression of the patient.28 In other studies,the incidence of the palmomental and the

snout reflexes was not significantly differentin patients with Parkinson's disease andhealthy, age matched control subjects.'Although a positive glabellar tap reflex is con-sidered to be an important diagnostic sign ofparkinsonism,'4 it is also found in patientswith intracranial disease who do not show anyother signs, or who show symptoms of aclearly symptomatic parkinsonism.36 In onestudy, the glabellar tap reflex correlated bestwith the extent of the lesion and not with thesite of the lesion.3 Several authors havereported the reversal of this reflex in patientsafter therapy with levodopa," 1215amantadine,II or lisuride'6; other authors,however, have not confirmed these findings.' 8In another study, the palmomental reflex wasfound to be even more reliable than theglabella reflex as a clinical indicator ofParkinson's disease.'3To summarise, the published findings and

conclusions on primitive reflexes in parkin-sonism are often confusing, controversial, ornot readily compatible. This is not because offalse diagnoses or heterogeneity of the patientgroups studied, but mainly because of a lackof compatibility of methodology used to elicitand score the primitive reflexes and the smallnumbers of (mutually different) reflexes inthe various studies.

Recently, we found that experienced neu-rologists differ considerably in how they elicitand judge primitive reflexes.'7 Reliable mea-surement in adult patients with neurologicaldisease therefore requires a very elaborateprotocol. A standardised protocol for thestudy of a 'primitive reflex profile' has notbeen applied in Parkinson's disease. Moststudies have examined only one, and rarelytwo or three, primitive reflexes.'-3 8 9The aim of the present study was therefore

to apply a standardised and semiquantifiedtest battery of 15 primitive reflexes to patientswith Parkinson's disease to determine theprevalence and the clinical value of thesereflexes, compared with healthy controls, bycorrelating them to parameters such as sever-ity and duration of the disease, cognitivefunctioning, and depression. The battery thatwas chosen was found to have high inter-observer and intra-observer reliability.'7 Theprimitive reflexes included: the glabellar tap;palmar and plantar grasp; palmomental andpollicomental; rooting; snout; suck; headretraction; nuchocephalic; asymmetrical tonicneck; mouth open finger spread (MOFS);

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and palmar and plantar support reflexes.Most of these are well known in research onneurological ageing.7 The last four reflexeshave potential value for use in adults.'819 Avariant of the glabellar tap reflex, thenasopalpebral reflex, was added to the bat-tery, because of its presumed clinical value inparkinsonism.3 20

MethodSUBJECTSTwenty-five patients with a diagnosis of pri-mary, degenerative Parkinson's disease wereselected at random from the neurological out-patient clinic. All had undergone an extensivegeneral and neurological examination, bio-chemical analysis and CT of the brain, toexclude other causes of parkinsonism.Twenty-five healthy control subjects werematched to the patients with respect to ageand sex.

All patients underwent the followingexaminations (table): the reflex battery; theWebster rating scale for severity of disease21;the Hoehn and Yahr scale for staging ofparkinsonism22; the global deterioration scale(GDS)23 and the mini mental state examina-tion (MMSE)24 for assessment of cognitivefunctioning; and the Zung depression scale.25The control subjects underwent a neuro-logical examination including the reflexes;none of them showed any neurological sign,or mental deterioration or depression inneurocognitive testing.

PROTOCOL OF THE PRIMITIVE REFLEX BATTERYBriefly, a basic position was described and thesubject was given instructions as to what wasexpected of him or her-for example, sittingor standing; eyes open or closed, etc.). Thesubject was not informed about the nature ofthe expected response, but was alwaysinformed about the nature of the stimulus inorder to prevent startle reactions, whichmight influence the required response. Everyreflex was measured at least three times, withabout two seconds between each elicitation,except for the glabellar tap and thenasopalpebral reflexes, which were appliedtwo times per second. All reflexes wereassessed for amplitude and persistence, asproposed by other investigators.413 If apt, thereflexes were elicited on both sides.

Table Characteristics ofpatients and control subjectsPatients Controls

Number of subjects 25 25Age (years) 66-5 (9-5) 67-5 (9-5)Age range (years) 40-84 40-82Sex 18 M17 F 18 M/7 FGDS 2-0 (0-9) 1.0MMSE 27-4 (2 4) N/AMMSE (range) 21-30 N/AZung depression scale 32-6 (8R0) N/AHoehn and Yahr 2-3 (0 9) 0Webster 11-5 (4 4) N/AParkinsonism since (years) 8-0 (6 2) N/ADiagnosed since (years) 6-4 (5 4) N/A

Unless indicated otherwise, mean values are given. Numbersin parentheses denote standard deviations.GDS = Global deterioration scale; MMSE = Mini mentalstate examination; N/A = not applicable.

SCORINGAmplitude and persistence of the reflex werescored separately. A three point scale for bothcharacteristics was used. The scoring was asfollows: for amplitude, 0 = absent; 1 = aweak to moderate response; and 2 = a strongresponse. A well defined description for theweak to moderate and strong amplitudes isgiven for each reflex. For persistence, 0 =absent; 1 = response for one to four consecu-tive times; and 2 = response for four or moreconsecutive times. The glabellar tap and thenasopalpebral reflexes were considered to bepresent but exhaustible after four to 10 con-secutive responses and to be persistent aftermore than 10 consecutive responses, respec-tively. This is in accordance with the pro-cedure followed by others.2 A detaileddescription of instructions, position, methodof elicitation, and scoring of each reflex isgiven elsewhere.26

ResultsThe prevalence of primitive reflexes inpatients and control subjects is shown in thefigure. The prevalence increased with age inthe control group (p < 0.01), but not in thepatient group. The average number ofreflexes per individual was, irrespective ofage, however, considerably higher in thepatients than in the control subjects: 4-6 and0-8, respectively. For patients younger than60 years this was 3 9 (SD 0 2), between 60and 70 years 5-4 (SD 0 5), and for thoseolder than 70 years 3-7 (SD 1 9). There wasno difference between men and women.

All but one of the reflexes occurred morefrequently in patients than in the control sub-jects. The overall difference in frequenciesper reflex was significant (p < 0 01). Theglabellar tap and snout reflexes occurred innearly all patients (96 and 92%, respectively).These reflexes were also present in 12 and20% of the control subjects, respectively. Thenasopalpebral reflex occurred in 88% of thepatients but in none of the control subjects.The palmomental and pollicomental reflexeswere also found more often in patients thanin the control group; so were the suck and leftnuchocephalic reflexes, albeit to a lesserextent. Only the left MOFS was present moreoften in the control subjects (20%) than inthe patients (4%). Six reflexes (asymmetrictonic neck, palmar and plantar grasp, headretraction, rooting, and plantar support) wereabsent in both groups.

In the control subjects, amplitudes werenever scored as 'strong' and only four out of21 responses were persistent (19%). In thepatients, the amplitude was scored as 'strong'six times, of which four were for the snoutreflex; more than half of the responses, how-ever, (64 out of 118) were scored as 'persis-tent' (54%). The most frequently persistingreflexes were the glabellar tap (19/24), thenasopalpebral (11/22), the snout (19/23), andthe suck reflexes (5/8). Only the persistenceof reflexes, not the amplitude, was related tothe patient group.

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Primitive reflexes in Parkinson's disease

Figure Percentage ofpatients with Parkinson'sdisease (left) andhealthy control subjects(right) showing primitivereflexes. Glab = glabellartap; Naso = nasopalpetralreflex; Palm =palmomental reflex;Poll = pollicomental reflex;Snout = snout reflex;Suck = suck reflex;MOFS = mouth openfinger spread reflex;Nuch = nuchocephalicreflex; SuPa = palmarsupport reflex.

GlabNaso

Palm LR

Poll LR

SnoulSuck

MOFS LR

Nuch LR

SuPa LR

I IIt

ttcI r n xs e n n r n rr

0

GlabNaso

Palm LR

Poll LR

SnoutSuck

MOFS LR

Nuch LR

SuPa LR

10 20 30 40 50 60 70 80 90 100% 0 10 20 30 40 50 60 70 80 90

The average number of reflexes did notincrease with the duration of the disease,which was estimated retrospectively after theinitial symptoms (range 2-25 years, mean

8&0, SD 6 2), or with the number of yearssince the diagnosis of Parkinson's disease hadbeen established by a physician (range 1-22years, mean 6-4, SD 5.4). Hoehn and Yahr,and Webster scores were closely related (p <0.01), but did not show a significant correla-tion with the number of primitive reflexes.The number increased with the GDS:patients in stage 1-2 (n = 18) showed an

average of 4-2 reflexes; patients in stage 3-4(n = 9) showed 5-6 (p < 0 01). MMSE rat-ings were also weakly related (p < 0-05).Depression did not correlate with reflexes,but it did with the time since the diagnosis(p < 0-05), was established. Age did not cor-relate with the number of reflexes, but itdid-slightly-with the Webster, Hoehn andYahr, GDS, and MMSE scores (p < 0 05).

DiscussionOnce an individual has definite symptoms ofParkinson's disease, some primitive reflexesshow up and persist. The number of reflexesdoes not increase with the duration or sever-

ity of the disease. The correlation with theMMSE and GDS is compatible with the viewthat these reflexes are a sign of diffuse cere-

bral dysfunction, rather than a symptom of adistinct neurological disease.3 6 9 10 27Our results confirm other findings con-

cerning the most frequently found reflexes.Some state that the persisting glabellar tapsign is probably the best correlative test inParkinson's disease.' 014 Gimenez-Roldan etaP3 found the palmomental reflex to be an

even more reliable clinical indicator. Ourresults are not in agreement with this, butthey do agree on the amplitude and persis-tence of the palmomental reflex. The (re-)appearance of the nasopalpebral reflex isinteresting, from an ontogenetic as well as

from a historical point of view.20 In our study,compared with healthy control subjects, thisreflex seems to have an almost equally greatsensitivity, and an even greater specificity forparkinsonism than the glabellar tap reflex.The snout reflex equals the glabellar sign as

to specificity and sensitivity. The asymmetry

of the nuchocephalic reflex was not associatedwith unilateral parkinsonism, in contrast tothe palmomental reflex in Maertens deNoordhout's study.4We could not test the negative correlation

between the glabellar tap and the palmomen-tal reflexes and dyskinesia reported by Iriarteet al,28 since too few patients showed dyskine-sia. As for the reversal of reflexes-for exam-

ple, the glabellar tap, after starting levodopa,lisuride, or amantadine treatment, we couldnot test this because our patients were on a

stable drug regimen. Levodopa was taken by56% of the patients, amantadine by 48%, andthe combination of both drugs by 16%. Theglabellar sign was present in 96% of our

patients, and 79% of these positive responses

showed persistence. According to some

authors, looking for these reflexes could givean objective, although indirect, evaluation ofthe patient's dopaminergic status.41' 12 Thiswas not confirmed by Huber and Paulson.'9Our findings do not support the view ofMessina et alP", and Klawans et a!2 about thehabituation or reversal of the glabellar sign.The present findings suggest that the

glabellar tap, nasopalpebral, and snoutreflexes, and especially their persistence, maybe of relevance in the examination of patientswith Parkinson's disease, in view of sugges-tions that persistence or amplitude, or both,are correlated with the degree of cerebraldegeneration.268101217 A standardised proto-col on how to elicit and score primitivereflexes is required for the study of a broadprofile of these signs in neuropsychiatric dis-orders.

1 Gossmann MD, Jacobs L. Three primitive reflexes inparkinsonism patients. Neurology 1980;30: 189-92.

2 Huber SJ, Paulson GW. Relationship between primitivereflexes and severity in Parkinson's disease. NeurolNeurosurg Psychiatry 1986;49: 1298-300.

3 Pearce J, Aziz H, Callagher JC. Primitive reflex activity inprimary and symptomatic parkinsonism. NeurolNeurosurg Psychiatry 1968;31:501-8.

4 Maertens de Noordhout A, Delwaide PJ. The palmo-mental reflex in Parkinson's disease. Arch Neurol 1988;45:425-7.

5 Jacobs L, Gossmann MD. Three primitive reflexes innormal adults. Neurology 1980;30: 184-8.

6 van Tiggelen CJM. The Bracha reflexes. Akt Gerontol1983;13: 195-200.

7 Jenkyn LR, Reeves AG. Signs of cortical inhibition inneuropsychiatric disorders. Psychiat Med 1984;1:389-405.

8 Bakchine S, Lacomblez L, Pallison E, Laurent M,Derouesnet C. Relationship between primitive reflexes,extra-pyramidal signs, reflective apraxia and severity of

persistent

m N~~~~~not persistentI

I

I

II

Icontrols

100%

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Vreeling, Verhey, Houx, JoUles

cognitive impairment on dementia of the Alzheimertype. Acta Neurol Scand 1989;79:38-46.

9 Jenkyn LR, Reeves AG, Warren T, et al. Neurologic signsin senescence. Arch Neurol 1985;42: 1154-7.

10 Girling DM, Berrios GE. Extrapyramidal signs, primitivereflexes and frontal lobe function in senile dementia ofthe Alzheimer type. Br_' Psychiatry 1990;157:888-93.

11 Messina C, Di Rosa AE, Tomasello F. Habituation ofblink reflexes in Parkinsonian patients under levodopaand amantadine treatment. J Neurol Sci 1972;17:141-8.

12 Klawans Jr. HL, Goodwin JA. Reversal of the glabellarreflex in Parkinsonism by L-Dopa. Jf Neurol NeurosurgPsychiatry 1969;32:423-7.

13 Gimenez-Roldan S, Esteban A, Abad JM. Reflejo palmo-mentoniano en enfermedad de Parkinson. ArchNeurobiol 1976;39:233-48.

14 Garland HG. Parkinsonism. BrMedJ 1952jan 19:153-5.15 Penders CA, Delwaide PJ. Blink reflex studies in patients

with parkinsonism before and during therapy. J NeurolNeurosurg Psychiatry 197 1;34:674-8.

16 Sandrini G, Alfonsi E, Martignoni E, Horowski R, NappiG. Effects of lisuride on blink reflex habituation inParkinson's disease. Eur Neurol 1985;24:374-9.

17 Vreeling FW, Verhey FRJ, Houx PJ, Jolles J. Primitivereflexes in healthy, adult volunteers and neurologicalpatients: Methodological issues. J Neurol 1993 (inpress).

18 Bronisch FW. Die Reflexe. Stuttgart: Thieme Verlag,1979:86-9.

19 Botez MI, Bogen JE. The grasp reflex of the foot andrelated phenomena in the absence of other reflex abnor-malities following cerebral commisurotomy. Acta NeurolScand 1976;54:453-63.

20 Simchowicz T. Ueber den Nasenaugenreflex und derNasenkinnreflex. Dtsch Z Nervenheilkd 1922;75:342-55.

21 Webster DD. A method of measuring the dynamic charac-teristics of muscle rigidity, strength and tremor in theupper extremity. IRE Trans Med Electr 1959;6:159-64.

22 Hoehn MM, Yahr MD. Parkinsonism: Onset, progressionand mortality. Neurology 1967;17:427-42.

23 Reisberg B, Ferris SH, Crook T. The GlobalDeterioration Scale (GDS): an instrument for theassessment of primary degenerative dementia (PDD).AmJPsychiatry 1982;139:1136-9.

24 Folstein MR, Folstein SE, McHugh PR. Mini-MentalState, a practical method for grading the cognitive stateof patients for the clinician. J Psychiat Res 1975;12:189-98.

25 Zung WWK, Durham NC. A self-rating depression scale.Arch Gen Psychiatry 1965;12:63-70.

26 Vreeling FW, Verhey FRJ, Jolles J. Protocol on the exami-nation of primitive reflexes: basic position, instructions,elicitation, response and scoring. Protocol: 87-0126Neuropsychology and psychobiology project. StateUniversity of Limburg, Maastricht, The Netherlands,1987.

27 Franssen EH, Reisberg B, Kluger A, Sinaiko E, Boja C.Cognition-independent neurologic symptoms in normalaging and probable Alzheimer's disease. Arch Neurol1991;48: 148-54.

28 Iriarte LM, Chacon J, Madrazo J, Chaparro P, Vadillo J.Blink reflex in dyskinetic and nondyskinetic patientswith Parkinson's disease. Eur Neurol 1989;29:67-70.

29 Huber SJ, Paulson GW. Influence of dopamine and dis-ease severity on primitive reflexes in Parkinson's disease.Eur Neurol 1989;29:141-4.

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