letters to the editor

Movement Disorders Vol. 7, No. 4, 1992, pp. 387-391 0 1992 Movement Disorder Society

Letters to the Editor

Idiopathic Torsion Dystonia

To The Editor: Fletcher et al. (Mov Disord 1991;6:304-309) present a

case-control study of idiopathic torsion dystonia (ITD), and they draw conclusions regarding the relationship between neonatal hypoxic-ischemic (H-I) brain injury and dystonia that require clarification.

The authors selected a group of patients with the primary dystonia phenotype who met several criteria, including the absence of neonatal neurologic abnormalities or delayed developmental milestones. Among these patients they made inquiries (apparently in the absence of records) regarding a variety of birth complications, including many minor obstetrical complications such as breech presentation, multiple births, instrumental or cae- sarean delivery, and nuchal cord. They apparently considered the presence of any one of these complications to represent an “abnormal birth.” They found no difference in the frequency of “abnormal births” between the dys- tonics and controls and conclude that there was no “evidence that birth trauma is associated with dystonia.” Further, they question the concept that neonatal H-I brain injury can, in some instances, lead to a close phe- nocopy of ITD (1,2).

The authors have not analyzed a group of patients that would allow them to examine the spectrum of neurologic signs which result from H-I injury at birth or which would permit examination of the relationship between this form of injury and the expression of dystonia, because none of these patients meet criteria for H-I at birth. The obstetric complications that the authors list as sufficient to con- sider a birth “abnormal” have not been found to be associated with cerebral palsy (CP) (3). It is thus not sur- prising that they have been unable to find an association between these trivial obstetric complications and the dystonia phenotype.

The authors are correct when they suggest that inade- quate criteria for neonatal H-I brain injury were used in our original report (1). The authors misrepresent that report, however, when they state that we had claimed that perinatal asphyxia may cause the appearance of the primary dystonia phenotype in adult life. In fact, the five cases we reported had the onset of dystonia in childhood.

In the original report and in our more recent one (2) in which we used more specific and stringent criteria for perinatal asphyxia, we observed that some of these children have an examination that closely resembles the primary dystonia phenotype. For example, patient 5 (2) had an Apgar of 0, required resuscitation, and had hypotonia and twitching in the neonatal period. Nevertheless, this child had only dystonia on examination through 1 1 years follow-up. Given the presence of this child’s neonatal neurologic abnormalities, he would have been excluded from the analysis by Fletcher et al., and he illustrates how

their series of patients is not suitable to judge the clinical features of dystonia following neonatal H-I.

The belief that perinatal H-I injury may result in a clinical picture resembling ITD is supported by early patho- logic observations that patients with a clinical picture characterized predominantly by dystonia had status marmoratus of the striatum. For example, Alexander (4) reported three patients with abnormal births and status marmoratus at postmortem who apparently had predominantly dystonia on examination and who were included as examples of torsion dystonia by Herz (5 ) .

Often among children with delayed-onset dystonia, there are subtle clinical clues or radiologic abnormalities (such as hemiatrophy) that permit distinction from the primary dystonia phenotype. Nevertheless, the resem- blance can be close enough that we continue to use the occurrence of perinatal asphyxia (2) as a criterion of exclusion for the diagnosis of ITD, particularly in genetic linkage studies. We do not use the occurrence of any of the minor obstetric complications that the authors studied as a criterion of exclusion for a diagnosis of ITD.

The authors downplay the relevance of neonatal H-I to any form of dystonia and cite the Collaborative Perinatal Project (6) to support their position. They neglect to add that, although the traditional view that all static enceph- alopathies of childhood are due to adverse perinatal events is certainly wrong, there is agreement that neonatal H-I is capable of damaging the infant brain, particularly the striatum, and it remains an important cause of chronic neurologic impairment (7-9). If one considers only children with dyskinetic CP, born at term, 84% have identifiable perinatal risk factors (10). Among children with dyskinetic CP, dystonia is the most prevalent and disabling involuntary movement (1 1).

Robert E. Burke Department of Neurology

Columbia University New York, New York

References 1 . Burke RE, Fahn S , Gold AP. Delayed-onset dystonia in

“static” encephalopathy. J Neurol Neurosurg Psychiatr 1980;43:789-797.

2. Saint-Hilaire M-H, Burke RE, Bressman SB, Brin MF, Fahn S . Delayed onset dystonia due to perinatal or early childhood asphyxia. Neurology 1991;41:21&222.

3. Nelson KB, Ellenberg JH. Obstetric complications as risk factors for cerebral palsy or seizure disorders. JAMA 1984;

4. Alexander L. The fundamental types of histopathological changes encountered in cases of athetosis and paralysis ag- itans. Research Publications of the Association for Re- search in Nervous and Mental Disease 1940;21:334493.

5 . Herz E. Dystonia. 111. Pathology and conclusions. Arch Neuroi Psychiatr 1944;52:2&26.

251 : 1843-1848.

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388 LETTERS TO THE EDITOR

6. Nelson KB, Ellenberg JH. Antecedents of cerebral palsy. N Engl J Med 1986;315:81-86.

7. Hill A, Volpe JJ. Seizures, hypoxic-ischemic brain injury and intraventricular hemorrhage in the newborn. Ann Neu- rol 198 I ; 10: 109-1 2 1 .

8. Paneth N. Birth and the origins of cerebral palsy. N Engl J Med 1986;315:124-126.

9. Nelson KB. What proportion of cerebral palsy is related to birth asphyxia? J Pediatr 1988;112:572-574.

10. Hagberg B, Hagberg G. Prenatal and perinatal risk factors in a survey of 681 Swedish cases. In: Stanley F, Alberman E, eds. Epidemiology of the cerebral palsies. Philadelphia: JB Lippincott, 1984:11&134.

1 1 . Kyllerman M, Bager B, Bensch J , et al. Dyskinetic cerebral palsy. Acta Paediatr Scand 1982;71:543-550.

Reply We are grateful to Dr. Burke for raising the vexed question of the relationship between possible perinatal asphyxia and the later development of neurologic dysfunction, specifically dystonia. There is little dispute with the observation that perinatal risk factors, including those re- garded as evidence of asphyxia, can be identified in many patients with athetoid CP who exhibit delayed motor milestones and the subsequent (sometimes delayed) appearance of a dystonic syndrome (1). What is at issue is whether a perinatal history thought to indicate asphyxia may predate, and thus be causally related to, the phenotype of ITD developing in childhood or early adult life on the background of normal motor development. This issue should not be confused with the arguably more problem- atic ones of defining either precise criteria for birth asphyxia or the relationship (if any exists) between perinatal asphyxia and CP.

The diagnostic criteria for significant perinatal asphyxia are controversial. We studied several other features of the birth history not mentioned by Burke, including prematurity and low birth weight, both of which are strongly associated with CP ( 2 ) , and also the presence of apnea and cyanosis at birth and admission to a special care unit for any reason. Although we agree that there is no perfect way of defining perinatal asphyxia, it seems likely that patients who were significantly asphyxiated (or were exposed to any other peri- or prenatal adverse in- fluence) would have reported one or more of the factors enquired about. Breech presentation and multiple births are not “minor obstetric complications”; both are associated with CP although the reason for this is unclear (293).

Dr. Burke agrees with our conclusion that the perinatal factors we analysed are not associated with the later development of an ITD-like phenotype. This is an important point because Burke and others previously claimed that the very same perinatal events (even in the absence of convincing evidence of H-I encephalopathy and abnormal developmental milestones) suggest that perinatal asphyxia has occurred and that this is the cause of “delayed onset dystonia” (DOD), which may resemble ITD (4). In their most recent report, the Columbia group described 10 patients with DOD (9, four of whom had delayed milestones and other neurologic features and thus clearly do not have the ITD phenotype. Of the four with normal

milestones, who could have been considered as possible cases of ITD using our clinical criteria, two had findings on investigation suggesting secondary dystonia (cases 2 and 8); they would thus have been excluded from our study. The only patients who “closely resemble the phenotype of ITD” are case 1, who had neonatal seizures following cyanosis at birth, with generalized dystonia presenting at the age of 5 years, and case 5, who had a similar birth history, segmental dystonia developing at the age of 14 years, and an EEG abnormality of uncertain significance. As pointed out by Coker (6), these patients were ascertained from a total population of 1,600 cases of all types of dystonia, making the significance of the birth histories of these patients somewhat suspect.

The introduction to our article makes it clear that we were analysing possible aetiological factors in ITD and it was never our intention to study “the spectrum of neurologic signs” due to H-I birth injury. Our aim was to ask how frequently a history of possible perinatal asphyxia (amongst other factors) is found in those with the phenotype of ITD, as compared to control subjects. As an absence of neonatal neurological abnormalities or delayed development does not exclude the possibility of birth asphyxia (7), such a history should be more common in patients if DOD genuinely masquerading as ITD repre- sents a significant clinical entity. In the event, there was no difference between patients and controls. Unless other case control studies provide convincing evidence to the contrary, anecdotal case reports should, in our view, be interpreted in this light.

N. A. Fletcher A. E. Harding

C. D. Marsden Institute of Neurology

London, England

References 1 . Kyllerman M. Dyskinetic cerebral palsy 11. Pathogenetic

risk factors and intrauterine growth. Acta Paediatr Scand

2. Stanley F. Social and biological determinants of the cerebral

3. Stanley F. Perinatal risk factors in the cerebral palsies. Clin

1982;71:551-558.

palsies. Clin Dev Med 1984;87:69-86.

Dev Med 1984:87:98-115. Burke RE, Fahn S, Gold AP. Delayed onset dystonia in patients with static encephalopathy. J Neurol Neurosurg Psychiatr 1980;43: 789-797. Saint Hilaire M-H, Burke RE, Bressman SB, Brin MF, Fahn S. Delayed-onset dystonia due to perinatal or early childhood asphyxia. Neurology 1991 ;41:21&222. Coker SB. Delayed-onset dystonia. Neurology 1991;41: 1704. Russman BS, Gage JR. Cerebral palsy. Current Problems in Paediatrics 1989;19:67-111.

Clinicopathological Observations in Multiple System Atrophy

To the Editor: We read with interest the paper by Hughes et al. (1).

They reported the clinicopathological finding in a patient

Movement Disorders, Vol. 7, No. 4, 1992

LETTERS TO THE EDITOR 389

with idiopathic Parkinson’s disease (IPD) and multiple system atrophy (MSA). The clinical diagnosis was that of IPD. They support their clinical impression with several points related to the mode of onset, response to L-dopa, pattern of dyskinesia, and the length of survival. This was one of the six MSA cases that was studied by these authors (1).

Over 23 (1968-1991) years we have conducted 77 au- topsies in parkinsonian cases seen by the same neurolo- gist (AHR). In 13 of those, the pathological diagnosis was MSA (2). We believe our series is the largest collection of MSA cases with both clinical and pathological studies. The clinical data including the response to L-dopa were recorded prospectively and in most cases there was a long follow-up (3). In one patient the combination of MSA and Lewy body pathology was noted. In this patient the Lewy body pathology was considered as incidental and the dominant clinical picture was that of MSA. Our data confirm that the response to L-dopa in the MSA is short lived (1).

Our experience, however, differs from their observations (1) in some respects. We have noted that tremor can be a prominent presenting feature in some MSA cases. One of our patients had unilateral tremor at the onset and this with time became quite severe and generalized. There was however a decline in the tremor severity with prolonged follow-up. Resting tremor was seen in 44% of our MSA cases (4).

Hughes et al. (1) also noted that generalized dyskinesias are rarely seen in MSA. Among our six treated cases, three developed dyskinesia-two focal and one generalized (5). Many MSA patients are not treated with adequate doses of L-dopa. The dyskinesias are dose-duration dependent side-effects (3) and MSA cases often receive short term L-dopa for reasons of lack of improvement and postural hypotension. This may explain why such side- effects do not occur more frequently.

Hughes et al. (1) claim that the 10-year survival noted in their case was excessive as the mean survival in MSA is 6 years. In 3 of our 13 (25%) patients, survival was 12, 14, and 23 years, respectively. The survival reported in their case (1) would be consistent with that due to IPD modified by MSA. A 10 year mean survival was reported prior to the L-dopa era (6), but a longer survival is ex- pected in an average IPD case today (7).

Their case (1) is unusual in that he had clinical features indicative of IPD beginning at age 63 and some indica- tions of the MSA (postural hypotension and bladder ur- gency) were noted at age 72. Usually the onset of MSA is at an earlier age than the onset of IPD (2). The clinical diagnosis of IPD is not always accurate (2,8) and a significant proportion of those clinically suspected of having IPD have an underlying MSA pathology (2). Some of the earliest clues to the MSA pathology in our experience are bladder dysfunction and postural hypotension (2), which retrospectively, were present in their (1) patient 9 years after onset.

S. Moghal A. H. Rajput

Department of Medicine, Division of Neurology Royal University Hospital, Saskatoon,

Saskatoon, Canada

1.

2.

3.

4.

5 .

6.

7.

8.

References Hughes AJ, Daniel SE, Lees AJ. Idiopathic Parkinson’s disease combined with multiple system atrophy: a clinicopathological report. Mov Disord 1991 ;6:342-346. Rajput AH, Rozdilsky B, Rajput A. Accuracy of clinical diagnosis in Parkinsonism, a prospective study- Can J Neu- rol Sci 1991;18:275-278. Rajput AH, Stem W, Laverty WH. Chronic low-dose levodopa therapy in Parkinson’s disease: an argument for delay- ing levodopa therapy. Neurology (Cleveland) 1984;34:991- 996. Rajput AH, Rozdilsky B, Ang L. Occurrence of resting tremor in Parkinson’s disease. Neurology 1991;41: 1298- 1299. Rajput AH, Rozdilsky B, Rajput A, Ang L. Levodopa effi- cacy and pathological basis of Parkinson syndrome. Clin Neuropharmacof 1990; 13: 553-557. Hoen MM, Yahr MD. Parkinsonism: onset, progression and mortality. Neurology 1967; 17:427-442. Kurtzke JF, Murphy FM. The changing pattern of death rates in Parkinsonism. Neurofogy 1990;4042-49. Forno LS. Pathology of Parkinsonism: a preliminary report of 24 cases. J Neurosurg 1966;24:266-271.

We thank Dr. Moghal and Dr. Rajput for their interest and contribution to the discussion of our case (1). With respect to the clinical spectrum of MSA we have re- viewed the clinical features of 23 cases with histologically-documented MSA collected at the Parkinson’s Dis- ease Society Brain Bank in London. The mean age at onset of disease was 57.1 years and the mean disease duration was 6.8 years. This compares with a mean age at onset of 62.4 years and mean disease duration of 13.1 years in 100 cases with histologically proven Parkinson’s disease collected at the Brain Bank over the same period. Certainly, the cases with survival up to 23 years cited by Moghal and Rajput are exceptional, the longest in our series was 11 years. Unlike their cases, prominent tremor at the onset of disease was not seen in our series. An akineticlrigid onset was most common, occurring in iso- lation in 14 patients and in association with mild tremor in another 7. Tremor-dominant pattern of disease was not seen in any of the cases. As suggested by Moghal and Rajput, early autonomic dysfunction seems to be a clue to the presence of MSA with seven of our cases showing autonomic dysfunction, usually involving the bladder, in the first year with an additional nine developing it later in the course of disease. We also found that misdiagnosis was common; 17 of 23 cases were diagnosed initially as Parkinson’s disease and in 9 the diagnosis was unchanged until after postmortem. Furthermore, of 100 consecutive cases with the antemortern clinical diagnosis of Parkin- son’s disease examined neuropathologically at the Brain Bank, 5 had MSA (2). In terms of levodopa response, nine of the 20 cases treated with an adequate trial of levodopa showed an initial response of more than 50% and in six cases some response persisted until death. Eleven cases developed levodopa-induced dyskinesia, which was isolated to the facial musculature in five, was generalized


390 LETTERS TO THE EDITOR

in five and occurred solely in an upper limb in 1. Motor fluctuations also occurred in 11 cases.

Although some clinical features are more specific for MSA, there is clearly significant overlap between the clinical spectrum of MSA and Parkinson’s disease. The case we described is most unusual, with the clinical history and histological findings supporting the coexistence of the two disease processes.

1 .

2.

To

Andrew J. Hughes Susan E. Daniel Andrew J. Lees

Institute of Neurology Parkinson’s Disease Society Brain Bank

London, England

References Hughes AJ, Daniel SE, Lees AJ. Idiopathic Parkinson’s disease combined with Multiple System Atrophy: a clinicopathological report. Mov Disord 1991;6:342-346. Hughes AJ, Daniel SE, Kilford L, Lees AJ. The accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinicopathological study. J Neurol Neurosurg Psychiatry 1992 $5: 18 1-184.

Cortical Activity Preceding Self-Initiated and Externally Triggered Voluntary Movement

the Editor: Papa et al. (1) have undertaken a series of experiments

showing an absence of the Bereitschaftspotential (BP) preceding externally triggered movements of the wrist. In contrast, we recorded a BP preceding hand and saccadic eye movements performed in response to both predictably and unpredictably timed visual stimuli (2,3). In these experiments we showed that variability in the time course and waveshape of the BP can result in its apparent absence when using the standard backaveraging technique.

For externally triggered movements, the BP must begin to develop before the arrival of the stimulus. If the stimulus timing is unpredictable, it follows that there cannot be a constant relationship between the onset of the BP and the onset of the movement. We found that in the period leading up to a stimulus to move, a negativity be- gins to develop prior to the subject’s estimate of the time of presentation of the stimulus. This negativity is then maintained at a constant level until the actual arrival of the stimulus. As a result, standard backaveraging from the time of movement will lead to a flat or reduced am- plitude potential. In the Papa et al. experiments, the in- terstimulus interval was approximately 10 s , which is too long for the subject to accurately predict the arrival time of the stimulus. In the cases of predictably timed stimuli and purely voluntary movement, the subject knows in advance when the movement will occur, leading to a more stereotyped BP waveshape which can be seen with standard backaveraging.

G . W. Thickbroom F. L. Mastaglia

Australian Neuromuscular Research Institute University of Western Australia

References Papa SM, Artieda J , Obeso JA. Cortical activity preceding self-initiated and externally triggered voluntary movement. Mov Disord I99 1 ;6: 2 17-224. Thickbroom GW, Mastaglia FL, Carroll WM, Davies HD. Cerebral potentials accompanying visually triggered finger movement in man. Electroencephalogr Clin Neurophysiol 1985 ;62:20!+2 18. Thickbroom GW, Mastaglia FL. Cerebral events preceding self-paced and visually triggered saccades. A study of presaccadic potentials. Electroencephalogr Clin Neurophys- i01 1985 ;62:277-289.

Reply We thank Drs. Mastaglia and Thickbroom for their in-

terest and comments in relation to our paper on movement-related cortical activity (1). They had previously reported similar findings (2 ) . The main aim of our work was to examine the relationship between different motor tasks and the Bereitschaftspotential (BP) on the light of a possible dual cortical organization of externally versus inter- nally initiated movements (3). Our results indicate that even complex tasks can be accurately performed without being preceded by the cortical activity that produces the BP. This suggests that the BP is mainly related with the expectation and preparation to move but not with the movement parameters. The observation of Thickbroom and Mastaglia that the BP develops only when the trig- gering stimulus is predictable is in keeping with our inter- pretation. We do not believe that our findings are due to technical reasons related with the backaveraging technique as suggested by Thickbroom and Mastaglia, rather we think, the presence or absence of the BP depends upon the motor strategy and consequently the cortical areas activated during the performance of a given task.

J. Artieda J.A. Obeso

Department of Neurology Clinica Universitaria

Pamplona, Spain

References Papa SM, Artieda J , Obeso JA. Cortical activity preceding self-initiated and externally triggered voluntary movement. Mov Disord 1991 ;6;3:217-224. Thickbroom GW, Mastaglia FL, Carroll WM, Davies HD. Cerebral potential accompanying visually triggered finger movement in man. Electroencephalogr Clin Neurophysiol 1985 ;62:209-2 18. Passingham RE. Two cortical systems for directing movements. In: CZBA Foundation Symposium 132. Motor areas of the cerebral cortex. New York: John Wiley & Sons, 1987: 15 1-164.

Dystonia in GM2 Gangliosidosis To the Editor:

We read with interest the case report by Nardocci et al. (1) of juvenile progressive dystonia associated with bio-


LETTERS TO THE EDITOR 391

chemical evidence of GM2 gangliosidosis secondary to hexosaminidase A deficiency. Although the authors state that this clinical picture has not previously been reported as the predominant and early feature, we should like to draw their attention to a brief communication in which we described a similar case (2). Our subject, a girl age 16 years, had presented with slowly progressive dystonia from age 4 years initially attributed to cerebral palsy, with additional anterior horn cell involvement developing later.

Both cases confirm the variety and overlap of clinical features that may occur as part of the spectrum of childhood GM2 gangliosidosis, which should be included in the differential diagnosis of symptomatic, secondary dystonia. Neurol Neurosurg Psychiatry 1988;51:446447.

R. J. Hardie J. A. Morgan-Hughes

University Department of Neurology Institute of Neurology The National Hospital

London, England

References

1. Nardocci N, Bertagnolio B , Rumi V, Angelini L. Progres- sive dystonia symptomatic of juvenile GM2 gangliosidosis. Mov Disord 1992;1:6447.

2. Hardie RJ, Young EP, Morgan-Hughes JA. Hexosaminidase A deficiency presenting as juvenile progressive dystonia. J


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