Introduction

Studies of somatosensory evoked potentials (SEPs) inneurological diseases have mostly concentrated on

short latency responses, although later componentshave occasionally yielded clinically useful informa-tion. Considerable uncertainty still exists regardingthe generators of many of these phenomena, but this

Karl NgStephen Jones

The ‘‘enhanced N35’’ somatosensoryevoked potential: its associationsand potential utility in the clinicalevaluation of dystonia and myoclonus

Received: 17 September 2005Received in revised form: 13 January 2006Accepted: 15 February 2006Published online: 4 February 2007

j Abstract In median nervesomatosensory evoked potentials,the cortical N35 amplitude some-times exceeds the P25 amplitude(C3’/C4’ referred to Fz; ‘‘enhancedN35’’ feature). Six hundred con-secutive patient median nerveSEPs were retrospectively analysedand compared with 27 controls.The feature was more often pres-ent in patients with dystonia(62%) than in patients with otherdisorders (22%; relative risk forthe condition 2.8; Fisher’s exact p= 0.003) or control subjects (7.4%;odds ratio 20; p = 0.0006). Simi-larly, the feature was more oftenpresent in patients with myoclo-nus (38%) than in patients withother disorders (22%; relative risk1.7; p = 0.02) or control subjects(odds ratio 7.5; p = 0.006).Therewas no clear relationship of thefeature to short latency SEPabnormalities except in cases ofmyoclonus. Further comparisonwas made of the characteristics of72 patients each, with and withoutthe feature, whose short latencySEP components were normal.The relationship of the feature to

dystonia or myoclonus held truein this case-controlled arm of thestudy. The sensitivity and speci-ficity were 65% and 78% respec-tively for any form of dystonia;43% and 79% respectively for anyform of myoclonus. The featurewas even more specific in bothconditions when compared withcontrols (93%). Most cases ofdystonia with an identifiable causein this study were of secondaryforms. It is known that this featureoften occurs in association with‘‘giant’’ SEPs in some myoclonicconditions. However, its occur-rence in dystonia may be a usefulnew finding in an established test,helping to identify a conditionwhere there is increasing evidencefor disordered sensorimotor inte-gration.

j Key words somatosensoryevoked potential Æ N35 Æmyoclonus Æ dystonia Æmultiple sclerosis

ORIGINAL COMMUNICATIONJ Neurol (2007) 254:46–52DOI 10.1007/s00415-006-0237-5

JON

2237

K. Ng Æ Dr. S. JonesDept. of Clinical NeurophysiologyThe National Hospital for Neurology andNeurosurgeryQueen SquareLondon WC1N 3BG, UK

K. Ng (&)Dept. of Neurology and NeurophysiologyRoyal North Shore HospitalSt LeonardsSydney 2065, AustraliaTel.: +61-2/99268344Fax: +61-2/99067719E-Mail: kng@med.usyd.edu.au

has not impeded efforts to find neurophysiologicalcorrelates for many neurological disorders.

Some associations have been known for a longtime such as the occurrence of ‘‘giant’’ cortical SEPsto median nerve stimulation in certain myoclonicconditions, as first described by Dawson in 1947 [1].This association has been further elucidated in theprogressive myoclonic epilepsies by other workersincluding Shibasaki et al. [2]. These authors describedan increase in the amplitude of the N20–P25 and P25–N35 waveforms in parietal to frontal derivations.

In our experience, we have noted that the secondnegativity (N35) exceeds the peak of the first nega-tivity (N20) frequently in these same conditions, evenwhen amplitudes are not abnormally large. Thisfinding translates to an N35 amplitude exceeding thatof the preceding P25 when measured peak-to-peak.This feature was seen in some patients referred to ourinstitution for investigation of myoclonus, as well asin non-myoclonic states including dystonia, but wasonly infrequently seen in control subjects. In thepresent study, we sought to define these and anyfurther clinical associations, thereby exploring thediagnostic utility of this feature in routine mediannerve SEP testing.

Materials and methods

The data from both arms of 600 consecutive patient median nerveSEPs collected over 4 years were retrospectively analysed. Therewere 249 males with a mean age of 45 years (SD = 15), and 351females with a mean age of 43 years (SD = 13). All studies wereperformed for referrals to the Department of Clinical Neurophys-iology at the National Hospital for Neurology and Neurosurgery.

Upper limb SEPs were recorded using Ag-AgCl disc electrodesattached to Erb’s point, second (Cv2) and seventh (Cv7) cervicalvertebrae, and scalp locations C3’, C4’ (2cms posterior to C3, C4)referred to Fz according to the standard 10–20 international systemof electrode placement and IFCN recommendations [3]. Recordingswere made with Bravo Evoked Potential v3.12 (Nicolet BiomedicalInc, Madison, WI, USA) with a bandwidth of 1Hz to 3kHz. Dataacquisition was of the first 50ms following the stimulus. Constantcurrent stimulation of 0.2ms in duration was delivered at 3.1Hz viaadhesive disc electrode pads (3MTM, St. Paul, MN, USA) at the wristover the median nerve with the stimulus intensity adjusted to elicita visible muscle twitch of the thumb. A ground electrode was placedon the scalp. Two hundred responses were averaged with 2–3repetitions and a grand average was computed off-line. The re-sponses were then compared with those of 27 normal controls(mean age 39, SD 8.7years; 13 males, 14 females).

Each SEP was visually assessed by one examiner (KN) for theaforementioned feature where the cortical N35 peak appeared toovershoot the N20 peak (amplitude N35 > P25). This was definedas an ‘‘enhanced N35’’ (Figure 1). The N35 peak itself was the firstnegativity demonstrated after N20 in the 50 ms latency range,excluding small deflections that appeared to be due to backgroundnoise or that did not constitute a distinct negative peak. Abnor-malities were noted in the short latency N9 (Erb’s), N13 (Cv2) andN20 (C3’/C4’) components by comparison with standard laboratorycontrols. These abnormalities constituted a delay in latency of the

elicited peaks, or an increased left-right latency difference morethan 2.5SDs above the control mean, or a relative amplitudereduction of > 50% for the N9 and N13 waveforms. P25 amplitudemeasured from the peak of N20 was considered abnormal when itexceeded 13 lV.

In the first part of the study, all patients were classified byreferral category. Major categories included definite or suspectedmultiple sclerosis (MS) and the hyperkinetic movement disordersmyoclonus and dystonia, but not undiagnosed jerks or spasms.Analysis of referral patterns revealed patients with apparentmyoclonus were investigated for the presence of ‘‘giant’’ potentials.Similarly, some patients with dystonia had co-existent myoclonusand were therefore also investigated for ‘‘giant’’ potentials. In bothinstances, proxy evidence of a deficit was initially sought in theshort latency components to try to demonstrate a secondary aeti-ology.

For the second part, two groups of 72 patients each, with andwithout the ‘‘enhanced N35’’ feature were randomly drawn fromthe same pool of subjects and studied in greater detail. These wereunselected except for the absence of short latency SEP abnormali-ties on this occasion, and P25 amplitude not being abnormallyenlarged as defined above. In this second part, a detailed perusal ofthe medical case notes was performed to determine the validity ofthe clinical diagnosis and to document the presence of upper limbsymptoms and signs. A similar scrutiny was applied to patientsfound to have hyperkinetic movement disorders when it emergedthat an association existed. Fisher’s exact probability test was usedand statistical significance was represented by p values < 0.05.

Results

The summary data for the patients-to-controls com-parison are presented in Tables 1 and 2. The ‘‘en-hanced N35’’ feature was present in 7.4% ofindividuals (and 5.6% of nerves) in the control group,and in 23.2% of individuals (and 17.6% of nerves) inthe patient population. This difference in the preva-lence of the feature approached significance forindividuals (p = 0.06). In the patient group, femaleswere more likely to display the feature than males(p = 0.04), but age was non-influential.

The largest referral category was suspected ordefinite MS, there being 216 such subjects (36% of thetotal). The second largest category was hyperkineticmovement disorders (68 patients, 11.3% of the total).The majority of the remaining patients exhibited

Fig. 1 Schematic view of median nerve cortical SEP waveform (C3’/C4’ referredto Fz) showing typical morphology (solid line) and ‘‘enhanced N35’’ feature(dotted line)

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some form of symptomatic sensory or motor distur-bance, with or without abnormal neurological signs,which did not satisfy existing criteria for suspectedMS although this often could not be absolutely ex-cluded [4]. Overall, the prevalence of an abnormalshort latency SEP was 25% for patients and 18% forarms tested.

The enhanced N35 feature was frequently presentin patients with hyperkinetic movement disorders thisprevalence being significantly greater than in theremainder of the patient population (46% vs 20%;p<0.0001). The relative risk for having the feature was1.7 in patients with myoclonus (p = 0.02), 2.8 indystonia (p = 0.003) and 3.2 when both conditions co-existed (p = 0.009). When these particular groupswere compared with controls, odds ratios for thefeature were 7.5 (p = 0.006), 20 (p = 0.0006) and 31 (p= 0.001) for the same categories respectively. Fig-ures 2 and 3 show the 95% confidence intervals forthese measures with the mean values above. Althoughwithin the patient population, suspected or definiteMS was significantly associated with the absence ofthe feature (p = 0.009), the prevalence of the featurewas still higher in this group (17.1%) than controlsubjects (7.4%) albeit not reaching significance (p =0.27).

Short latency SEP abnormalities were not signifi-cantly associated with the feature, even within thedefinite or suspected MS group (Table 3). A unilateral‘‘enhanced N35’’ feature revealed no greater tendencyfor an SEP abnormality to occur from stimulation ofthe same side. However, patients with hyperkineticmovement disorders were more likely as individualsto have an SEP abnormality associated with the fea-ture. This held for patients with myoclonus alone, theonly subgroup with sufficient numbers for this anal-ysis.

Table 1 Prevalence of the ‘‘enhanced N35’’ feature in patients and controls

With feature No feature p-value

ControlsTotal (n = 27) 2 (7.4%) 25Mean age (years) 39 39Gender (male:female) 2:0 11:14

All patientsTotal (n = 600) 139 (23.2%) 461 p = 0.06a

Mean age (years) 43 45Gender (male:female) 47:92 202:259 p = 0.04b

a Fisher’s exact test for feature prevalence in patients vs controlsb Fisher’s exact test for feature prevalence by gender

Table 2 ‘‘Enhanced N35’’ feature prevalence - comparison within patients and with controls

Disorder Proportion (%)with this feature

p-value for differencea

in proportion compared toother patients

p-value for differenceb

in proportion comparedto controls

Hyperkinetic movement disorderMyoclonus 18/48 (37.5) p = 0.02 p = 0.006Dystonia 8/13 (61.5) p = 0.003 p = 0.0006Myoclonus and dystonia 5/7 (71.4) p = 0.009 p = 0.001

Suspected or definite MS 37/216 (17.1) p = 0.009c p = 0.27

a p value for the relative risk for having the feature in patients with the specified disorder vs patients without the disorderb p value for the odds ratio for having the feature in patients with specified disorder vs controlsc associated negatively with the featureMS = multiple sclerosis

0.0

2.5

5.0

7.5

Myo Dys Myo+Dys MS

1.0

1.7

2.8

3.2

0.64

Rela

tive

risk

Fig. 2 Relative risks for the ‘‘enhanced N35’’ feature for each disordercompared to patients without that disorder

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Overall, the sensitivity and specificity of the featurefor patients with any form of myoclonus were 42%(95% CI 29–56%) and 79% (95% CI 75–82%)respectively compared with patients with other dis-orders; corresponding values for patients with anyform of dystonia were 65% (95% CI 41–85%) and 78%(95% CI 75–82%) respectively. The specificity rose to93% (95% CI 76–99%) for either condition when thefeature prevalence was compared with that in healthycontrols.

Table 4 shows the prevalence of the clinical cate-gories in equal numbers of 72 patients with andwithout the feature, who lacked abnormalities in shortlatency SEPs. In this portion of the study, more de-tailed clinical information was derived from recordsof past medical history and neurological examination.As a result of this selection and scrutiny of thebackground co-morbidities, there were several furtherpatients identified with myoclonus and/or dystonia.The association of the feature with movement disor-ders remained significant for myoclonus (p = 0.01)and for dystonia (p = 0.009), while the negativeassociation with definite or suspected MS previouslyidentified was no longer significant (p = 0.09). Onstudying patients’ symptoms in the relevant upper

limb, a negative association with documented non-discriminated sensory symptoms emerged, but thiswas not the case for objective clinical sensory signs(Table 5). No relationship was found with the pres-ence of motor symptoms or pyramidal signs. Thecorresponding odds ratios are displayed in Fig. 4.

A detailed review of the available clinical recordsindicated an identifiable cause in 10 dystonic and 34myoclonic patients (Table 6). It is apparent that mostof the causes found for dystonia were secondaryforms with a few cases of paroxysmal dystonia mak-ing up most of the rest.

Discussion

The ‘‘enhanced N35’’ feature is uncommonly seen inthe normal population. Although our definition isarbitrary, it is an easily discerned phenomenon withina standard investigation in regular clinical use. Itsoccurrence in myoclonus is already recognised, butthis is the first study to our knowledge that hasdemonstrated an association of the ‘‘enhanced N35’’feature with dystonia.

There are several findings in this study that arenoteworthy. Firstly, there was no significant associa-

-2.5

0.0

2.5

5.0

7.5

7.5

20

31

2.6

Log e O

R

Myo Dys Myo+Dys MS

Fig. 3 Loge odds ratios for the ‘‘enhanced N35’’ feature in patients vs controls

Table 3 The relationship of the ‘‘enhanced N35’’ presence with short latencySEP abnormalities

Proportion (%)with SEP abnormality

With feature No feature Significance

All patients 36/139 (25.9) 115/461 (24.9) p = 0.82Hyperkinetic movement disorder

Myoclonus alone 7/18 (38.9) 3/30 (10.0) p = 0.03Dystonia alone 2/8 (25) 1/5 (20) p = 1.00Myoclonus and dystonia 0/5 (0) 1/2 (50) p = 0.29

With suspected ordefinite MS

12/37 (32.4) 49/179 (27.4) p = 0.55

Table 4 Case control comparison of ‘‘enhanced N35’’ prevalence for patientswithout short latency SEP abnormalities by disorder

With feature(n = 72)

No feature(n = 72)

Significance

Mean age (years) 45 44Gender M:F 26:46 31:41Myoclonus alone 15 4 p = 0.01Dystonia alone 12 2 p = 0.009Myoclonus and dystonia 3 2 p = 1.00Definite or suspected MS 15 25 p = 0.09

Table 5 Case control comparison of the ‘‘enhanced N35’’ for patients withoutshort latency SEP abnormalities by symptom/sign

With feature(n = 72)

No feature(n = 72)

Percentage difference

UL symptomsSensory 35 51 p = 0.01*

Large fibre 35 46 p = 0.09*Small fibre 5 7 p = 0.76

Weakness 15 15 p = 1.00UL signsSensory

Large fibre 2 1 p = 1.00Small fibre 8 9 p = 1.00

Pyramidal 2 7 p = 0.17*

* negatively predictiveFive patients had both sensory and motor symptoms: 5 with and 2 without thefeature had both large and small fibre symptoms

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tion between short latency SEP abnormalities and thepresence of the ‘‘enhanced N35’’. This would implythat there is no strong relationship of this phenome-non to any dysfunction in the lemniscal systemrevealed by the upper limb short latency response.The phenomenon may therefore represent corticalprocessing of information conveyed through thissame pathway.

In previous interference experiments in man, itwas demonstrated that continuous cutaneous tactilestimulation in the form of light touch applied to thepalm of the hand produced a similar SEP effect innormal subjects [5]. The absence of such an effect forpainful and thermal stimulation in that study sug-gested that the changes may reflect ‘‘saturation’’ orbuild-up of inhibition at synapses of the dorsal col-umn/medial lemniscal pathway arising from the inputof cutaneous touch receptors.

The phenomenon seen in our study could well beanalogous to the effect of interfering cutaneous input.Despite considerable controversy the cortical com-ponents of the median nerve SEP are widely believedto be a summated response from tangential (Brod-man’s area 3b) and radial dipoles according to Alli-son’s model (Brodman’s area 1) [6]. The P25identified in the present study is likely to represent acombination of the P30 generated in area 3b (some-times called P27) and the P25 (also called P22) gen-erated in area 1. We postulate that the enhanced N35may be part of a broad negativity following the P22peak in this particular montage.

In normal subjects, the effect of vibration is toincrease the degree of presynaptic inhibition of Iatraffic, a compensatory effect that may be diminishedin dystonia [7] leading to an enhanced tonic vibrationreflex (TVR). Cutaneous input is known to producethe opposite effect by increasing the degree of pre-synaptic inhibition and subsequently depressing the

TVR. If the changes occurring in dystonia were beingmimicked in the aforementioned interference studieson normal subjects by continuous cutaneous stimulieffectively reducing or gating the amount of cutane-ous (type II fibre) input derived from the electricalvolley, the net result may be reflected in the ‘‘en-hanced N35’’ feature observed in both our studies.

Most of our cases of dystonia were ‘‘symptomatic’’or ‘‘secondary’’ reflecting the referral bias of clini-cians seeking confirmation of a CNS abnormality.There were also several cases of paroxysmal dystoniaamongst this group but these did not necessarilypossess the most prominent N35 enhancement.

Where the features of myoclonus or dystonia werenoted only on one side, there was no greaterenhancement of the N35 waveform from stimulation

-2.5

0.0

2.5

5.0

4.5

7.0

1.5

0.5 0.39

1.5

myo dys myo+dys MS symptoms signs

loge

OR

Fig. 4 Loge odds ratios for the ‘‘enhanced N35’’ (72 patients with and 72without the feature) in case control study

Table 6 Prevalence and laterality of the enhanced N35 feature according tothe aetiology of dystonia and myoclonus

Aetiology No. No. with featureand laterality offeature

Dystonia alonePKD 3 1 (bilateral)PNKD 1 1 (unilateral)Probable CBD 1 1 (bilateral)Chr 45, XY, t(13–18) 1 1 (bilateral)?Adrenoleukodystrophy 1 0Anti-BG antibody + ve 1 1 (unilateral)Neuroferritinopathy 1 0Segmental isolated tongue dystonia 1 0Dystonia with myoclonus?SCGE 2 0?Parkin gene mutation 1 1 (bilateral)MyoclonusIndeterminate cause 12 2 (1 unil, 1 bilat)Epileptic myoclonus

Juvenile myoclonic epilepsy 1 1 (unilateral)Benign adult familialmyoclonic epilepsy (�BAFME’)

1 1 (bilateral)

Unclassified 1 0Symptomatic

Corticobasal ganglionic degeneration 3 0Idiopathic Parkinsons disease 2 0Multiple systems atrophy 1 0Other Parkinsonian syndrome 1 0Alzheimer disease 1 0Sporadic Creutzfeld-Jacob disease 1 0Post-infectious 1 0Lithium toxicity 1 1 (bilateral)Post-anoxic 1 1 (unilateral)Mitochondrial cytopathy with PME 1 1 (bilateral)Coeliac disease 1 1 (bilateral)HIV 1 1 (unilateral)

SpinalPropriospinal 3 3 (unilateral)Segmental 1 0

PKD = paroxysmal kinesogenic dystonia; PNKD = paroxysmal non-kinesogenicdystonia; CBD = corticobasal ganglionic degeneration; chr = chromosome(translocation); BG = basal ganglia; SCGE = epsilon sarcoglycan gene muta-tion; DR = dopa responsive; PME = progressive myoclonus epilepsy

50

of that arm than in the clinically normal contralateralarm. Although it may be possible to derive moresensitive or specific criteria of N35 enhancementbased on parametric measurement of N35:P25amplitude ratios, in our study, only 4 cases ofmyoclonus, 3 of dystonia and one of both conditionswere discriminated on the basis of 2.5 standarddeviation limits. In these cases, one may expect thatthe feature was more prominent on the side ofinvolvement but here, lateralisation was correct in 2cases and incorrect in one. The feature was only seenunilaterally in 5 patients with generalised clinicalsigns using this methodology. This failure to dem-onstrate an effect of laterality may have occurredin this study group because the majority of thediagnoses implied subclinical involvement of thecontralateral side despite predominantly unilateralmanifestations.

Animal work has revealed that sensory inputs forbasal ganglia may be distinct from the lemniscalpathway [8]. There is also evidence for gating oflemniscal and extralemniscal systems by the basalganglia which may occur at several levels. In addition,SEP responses to paired stimuli delivered to adjacentnerves have suggested reduced spatial centre/sur-round inhibition in dystonia [9]. It is not known howthis disordered spatial processing might relate to ourobservations studying solely median nerve responses.

It might be speculated from our findings in dys-tonia and myoclonus, that the inputs that contributeto cortical SEPs may be dysfunctionally gated by thebasal ganglia, bringing about the phenomenon ofrelative N35 enhancement. In the area of dystonia inparticular, there has been much study both in thesensory and motor domain focusing on disturbedsensorimotor integration or lack of motor controlinhibition [10]. A widely held view is that this is adisorder whereby automatic and highly trainedmovements become abnormal in response to relevantsensory inputs, perhaps resulting from alteration ofreceptive fields at thalamic and cortical levels. This ismost apparent in the literature in the investigation ofpatients with primary forms of the disorder such aswriter’s cramp but a similar process may be present inpatients with secondary forms. The sensory systemaberration which our findings imply may be second-ary to putaminal deficits which may be exerting agating effect at the central level. Secondary forms ofdystonia most frequently arise from putaminal lesionswhen these are discrete.

Because this study used an Fz reference, it becomesnecessary to heed previous studies of frontal SEPphenomena at these latencies utilising non-cephalicreferential montages. Although separate recording ofpre- and post-central SEPs has shown clear evidenceof N30/P30 dissociation in parkinsonism [11], the

evidence in dystonia is controversial. The frontal N30was shown in one study to be enhanced in dystonia[12] and N30 lateralisation was also seen in torticollis[13]. However, a smaller N30 peak was noted in onestudy of torticollis [14] and also in hand dystonia[15], the latter possibly related to higher stimulationfrequencies. Rather than measuring just the peakswhich are unlikely to represent unitary underlyingprocesses even when the pre- and post-central wave-forms are studied separately, the present montageactually displays the difference between pre- andpost-central activity at every time point, and confirmsthat there tends to be an anomaly in dystonia, even ifit is not specifically at the N30 peak. Our finding isunlikely to be related to any enhancement of thefrontal N30, as this would be likely to yield theopposite effect to N35 enhancement. This is becausethe N30 would appear as a positive deflection in a C3’/C4’-Fz derivation, tending to cancel out the N35. It isinteresting to note that more recent intracranialrecordings suggest that the frontal N30 is not gener-ated in the supplementary motor area as previouslythought, but is likely to arise from hyperpolarisationin motor area 4 [16]. This clearly may be veryimportant in our understanding of the coupling ofsensory to motor systems, and how links betweenthese pathways may be disordered in dystonia.

‘‘Giant’’ SEPs, usually defined by enlarged P25amplitude, are known to occur in certain forms ofcortical reflex myoclonus. In our experience, ‘‘giant’’SEPs are often accompanied by an ‘‘enhanced N35’’feature. Our findings in myoclonus could suggest thatan expanded definition of the ‘‘giant’’ SEP shouldinclude not just absolute criteria of amplitude butrelative measures like that used in this definition ofthe ‘‘enhanced N35’’. In the myoclonus alone sub-group, the association of the feature with abnormalshort latency SEP components was just significant,probably reflecting the high prevalence of short la-tency SEP abnormalities in secondary causes ofmyoclonus, irrespective of the enlargement of latercomponents. Two cases only of myoclonus were feltto be spinal in origin; one propriospinal, interestinglywith the ‘‘enhanced N35 feature’’, and the other seg-mental without the feature.

It should be noted that despite the relatively lowprevalence of the feature within the patient groupwith suspected or definite MS, a larger percentage ofsuch affected individuals had the feature (17.1%)when compared with healthy controls (7.4%), albeitthis not reaching statistical significance. These pa-tients and those with hyperkinetic movement disor-ders cannot fully account for the excess of patientswith the feature in our patient population as com-pared with controls. Therefore, there may be otherconditions or factors in our patient population that

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facilitate its appearance. We also do not have a sat-isfactory explanation why females in this patientpopulation were more likely to have the feature thanmales.

Despite an abundance of techniques for the eval-uation of dystonia in the research setting, theseinvestigations can prove cumbersome or may beunavailable to most clinicians. Essentially, dystoniaremains a clinical diagnosis. In the absence of a ‘‘goldstandard’’ investigation, several lines of investigationcontribute to the body of evidence implying thelikelihood of an organic phenomenon. Although rel-atively rare, psychogenic forms of the condition exist[17]. Patients with a dystonic tremor may also havevery few or no dystonic features apparent and thisfinding may therefore also be useful.

In conclusion, although there are limitations in thistype of study for the evaluation of cortical SEP gen-erators, our definition of the ‘‘enhanced N35’’ featuremay prove a useful test for the investigation ofhyperkinetic movement disorders as it utilises a fre-quently practised and accepted montage. We haveshown in this study drawn from a large patient

database that the feature is common in dystonia andmyoclonus, and uncommon in healthy subjects. It hasa moderate sensitivity (65%) and higher specificity(78% within patients; 93% against controls) for dys-tonia, a condition usually diagnosed clinically. Addi-tionally, it may be of use in investigating myoclonicphenomena in order to complement available stan-dard neurophysiological techniques. For both disor-ders, there could be a higher discriminative value indifferentiating them from non-organic conditionswhere the prevalence of the feature is more likely toapproach that in the normal population. Perhaps fordystonia, this may therefore be most useful in pri-mary forms of the condition such as writer’s crampand torticollis, and further similar studies in theseparticular subtypes would be useful. It should never-theless be noted that the ‘‘enhanced N35’’ findinghas a low positive predictive value in an unselectedpatient population.

j Acknowledgements We thank Laura Fabiano, and Philip Allen,Department of Clinical Neurophysiology; Hilary Watt, medicalstatistician for the Institute of Neurology.

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