Letters, Correspondence, Book reviews, Correction 129 of acute diarrhoea, commonly precedes the Repetitive transcranial magnetic Table Neuropsychological tests and PANSS development of Guillain-Barré syndrome.5 stimulation in the treatment of chronic scores There is a close association between axonal negative schizophrenia: a pilot study Guillain-Barré syndrome and antecedent C Test Mean (SD) .5 The antecedent infectious jejuni Recently, a new technology known as repeti- Block design Pre 49 (11.95) NS symptom was diarrhoea in three of five tive transcranial magnetic stimulation Post 50 (8.69) patients with axonal Guillain-Barré syn- (RTMS) has been developed.1 In 1994, the Trail making test Pre 38.3 (9.83) NS drome described by Feasby et al.3 Observa- use of magnetic stimulation in clinical A Post 42.6 (14.1) tions by GriYn et al4 confirmed that AMSAN was suggested.2 Since then, it has Trail making test Pre 38.3 (4.5) NS follows C jejuni infection. Serum samples B Post 41 (10.03) been used in the study or treatment of Inmediate visual Pre 50.5 (4.82) NS from patients with axonal Guillain-Barré obsessive-compulsive disorder, conversion reproduction Post 54.8 (11.2) syndrome subsequent to C jejuni enteritis disorder, schizophrenia, and particularly, Delayed visual Pre 46.19 (8.23) p<0.05 often have IgG class autoantibodies to depression.3 reproduction Post 53.8 (12.64) gangliosides GM1, GM1b, GD1a, or Our pilot study aimed to assess the possible Inmediate verbal Pre 54 (7.46) NS paired GalNAc-GD1a in the acute phase of the adverse eVects of this treatment in chronic Post 59.5 (10.03) illness,6 and there is molecular mimicry schizophrenic patients with severe negative associates Delayed verbal Pre 8.8 (1.1) NS. between these gangliosides and the lipopoly- symptoms; to evaluate if direct RTMS of the paired Post 8.8 (1.17) saccharides of C jejuni isolates from patients prefrontal cortex might improve negative associates with Guillain-Barré syndrome.6 This ganglio- symptoms or cognitive impairments4 in pa- PANSS-PG Pre 37.67 (11.15) NS side mimicry may trigger high production of tients with chronic schizophrenia; and Post 36.5 (11.47) the IgG antiganglioside antibodies, and these thirdly, to note if RTMS might modify the PANSS-N Pre 31.67 (8.26) p<0.02 autoantibodies may cause motor nerve dys- deficit in prefrontal cortical activity, often Post 27.83 (8.47) PANSS-P Pre 16.83 (7.28) NS function in patients with GBS. referred to as hypofrontality, long established Post 15.33 /7.55) Interestingly, Hagensee et al7 reported a in schizophrenia,5 specially under conditions case of “C jejuni bacteremia and subsequent of task activation. Pre=pretreatment; Post=post-treatment; PANSS= Guillain-Barré syndrome” that occurred in a Six right handed patients with chronic positive and negative syndrome scale; PG=general patient with chronic graft versus host disease schizophrenia were identified at the outpa- psychopathology scale; N=negative scale; after allogenic bone marrow transplantation. tient psychiatric service of the Hospital Clínic P=positive scale. Because there was acute flaccid of Barcelona. There were two men and four associated with sepsis, some physicians might women (mean age 39). ses. All patients tolerated the RTMS well, have diagnosed critical illness polyneuropa- Exclusion criteria included alcohol or sub- with minimal side eVects (mild headache and thy. Conversely, the existence of this case stance abuse dependence disorder in the past tinnitus). strongly suggests that some diagnoses of 5 years, focal neurological findings, systemic Initial SPECT of one patient was reported critical illness polyneuropathy should actually neurological illness, taking cerebral metabolic to be normal, showing no evidence of hypo- be axonal Guillain-Barré syndrome or activator or vasodilator medications, electro- frontality. The remainder of the patients AMSAN. Our hypothesis of the nosological convulsive therapy within 6 months, and sig- showed hypofrontality on the initial neuroim- relation between critical illness polyneuropa- nificant abnormal findings on laboratory aging. The results after RTMS indicated no thy and axonal Guillain-Barré syndrome is examination. change in the hypofrontality. shown in the figure. Serum IgG antibodies All patients were taking neuroleptic drugs, Negative symptoms showed a general against GM1, GM1b, GD1a, or GalNAc- but a stable dose for at least 3 months was decrease for all patients (table). Significance GD1a could be used as immunological required. All patients were studied oV benzo- (p<0.02) was noted on the PANSS negative markers for axonal Guillain-Barré diazepines for at least 1 week before begin- symptoms subscale. These patients seemed syndrome.6 To examine the aetiology of criti- ning the treatment. During the RTMS, to be more sociable than when originally cal illness polyneuropathy and its nosological psychotropic medications were continued at seen. Nevertheless, clinical eVects of the relation to axonal Guillain-Barré syndrome, it the initial dosage. RTMS were subtle and diYcult to distinguish is necessary to investigate whether patients All patients were admitted to hospital. from those derived from the supportive envi- Inpatients underwent the UKU side eVects ronment of the psychiatric ward. with critical illness polyneuropathy have anti- 6 ganglioside antibodies during the acute phase scale, the positive and negative syndrome With regard to the neuropsychological bat- of the illness. scale (PANSS), and a neuropsychological tery, we found a general improvement in all battery, the day before beginning the treat- post-treatment scores (table), but only de- NOBUHIRO YUKI ment and at the end of the treatment. The layed visual memory achieved significance KOICHI HIRATA UKU scale was also administered after each (p<0.05). This feature might be basically Department of , session. explained by improvement of attention, Dokkyo University School of Medicine, Japan An equivalent neuropsychological battery specifically of the maintenance of attention, Correspondence to: Dr Nobuhiro Yuki, Depart- was used on both occasions, which consisted which allows the correct function of the ment of Neurology, Dokkyo University School of of the block design subtest of the Wechsler working memory. Thus, although there are Medicine, Kitakobayashi 880, Mibu, Shimotsuga, adult intelligence scale, the trail making tests methodological limitations regarding the Tochigi 321–0293, Japan. A and B, the FAS verbal fluency test, and two power of our conclusions, it is certain that subtests of the Wechsler memory scale (the there has been an improvement in the atten- visual memory reproduction and the verbal tional capability. 1 Bolton CF, Laverty DA, Brown JD, et al. Critically ill polyneuropathy. Electrophysiologi- paired associates subtests). We found that all patients (except one, who cal studies and diVerentiation from Guillain- A brain SPECT study was performed was always within the normal range) dimin- Barré syndrome. J Neurol Neurosurg Psychiatry using a rotating dual head gamma camera, ished their number of perseverative answers 1986;49:563–7. 2 Zochodne DW, Bolton CF, Wells GA, et al. fitted with high resolution fanbeam collima- and errors on WCST (items characteristically Critical illness polyneuropathy. A complication tors. Two 99mTc-HMPAO SPECT scans with altered in schizophrenia) after the RTMS. of sepsis and multiple organ failure. Brain cognitive activation, such as the Wisconsin However, significance was not achieved on 1987;110:819–42. card sorting test (WCST), were performed any WCST scores. 3 Feasby TE, Gilbert JJ, Brown WF, et al.An acute axonal form of Guillain-Barré polyneu- on each patient (24 hours before the Two patients who initially did not perform ropathy. Brain 1986;109:1115–26. beginning of the treatment and 24 hours after any categories on WCST, after the treatment, 4GriYn JW, Li CY, Ho TW, et al. Pathology of the last session). achieved one category, a possible indication motor-sensory axonal Guillain-Barré syn- RTMS was given with a Mag Pro magnetic of improvement of their abstract thinking. drome. Ann Neurol 1996;39:17–28. 5 Rees JH, Soudain SE, Gregson NA, et al. stimulator, 5 days a week, during 2 weeks, at This change leads us to consider a research Campylobacter jejuni infection and Guillain- a dosage of 20 Hz for 2 seconds, once per strategy previously reported, in which the Barré syndrome. N Engl J Med 1995;333: minute for 20 minutes at 80% motor thresh- WCST is used as a screening test for selecting 1374–9. old. The motor threshold was determined by schizophrenic patients. Those initially achiev- 6 Yuki N. Anti-ganglioside antibody and neu- ropathy. Review of our research. J Periph Nerv visualisation of finger movement. A butterfly ing low category scores would be compared Syst 1998;3:3–18. magnetic coil was placed tangential to the to higher category scorers in an eVort to 7 Hagensee ME, Benyunes M, Miller JA, et al. orbital area, on the C3 and C4 EEG point. identify a subgroup most likely to benefit Campylobacter jejuni bacteremia and Guillain- An important finding of this study was that from RTMS. Barré syndrome in a patient with GVHD after allogenic BMT. Bone Marrow Transplant 1994; RTMS may be given to stable schizophrenic Taking into account these mild improve- 13:349–51. patients without exacerbating their psycho- ments together, and the lack of changes in 130 Letters, Correspondence, Book reviews, Correction hypofrontality after treatment, we are consid- the alien limb. Not believing that you are any attempt to explain this finding occurs in the ering extending the treatment course to 20 more in control of a limb is not likely to be a context of fear. It may be that our apprehen- sessions, each at 30 Hz for 1 second, at 90% pleasant experience. sion leads us to misinterpret innocent reflex- of motor threshold. It was also suggested that Those with alien hand syndrome seem to ive acts of our hands, such as scratching or other positions of the coil and other kinds of jump to extremely negative conclusions con- rubbing, as malevolently inspired. Plus it coils might give better results. cerning the intent of the limb. Typically, as in could be that our interpretation of spiteful The clinical change in our cohort after the the report of Ay et al, the common belief is possession in turn inspires the hand itself, RTMS could be attributed to both the treat- that the limb has deeply malevolent inten- only this is beyond our conscious awareness. ment and the supportive environment of the tions towards the victim. It may therefore be that we need to believe psychiatric ward, and even to enhance It is this aspect of alien hand syndrome that in our own and personal control over compliance to medication during hospital I suggest also needs incorporating into its our acts, because if we did not, we might find admission. We are aware that the small sam- neurological explanations, and which pro- the experience of our bodies acting as if we ple size and lack of controls compel a very vides a clue as to why our everyday merely came along for the ride, too frighten- careful interpretation of the results. experience of being in charge of our bodies, ing. Also, we may no longer believe that our Nevertheless, in the light of these, we suggest and so initiating all personal action, itself has bodies or its relevant parts belong to us. All further controlled studies of the eYcacy of a neurological basis. In other words, while the neurologists who have reported alien hand RTMS in negative symptoms of schizophre- brain is the seat of all our actions and experi- syndrome remark on how psychologically nia, not only as an add on technique but also ences, there is also a part of our nervous sys- disturbing the symptom is for the patient. as a sole therapeutic procedure. Research on tem which is responsible for our belief that we Psychiatrists would be interested in the RTMS also requires some controlled studies have free will over our behaviour. Patients parallels between alien hand syndrome and aimed to the complexity of the methodology with alien hand syndrome think that they are the “passivity phenomena” of schizophrenia, (dosage, duration, and localisation), as this no longer in control of a limb because the plus the fact that the two diseases may share 4 form of intervention may prove to be an eco- part of the brain that gives us the sensation of pathology, could go some nomical and convenient therapy in treating control over our bodies has been damaged. way to explaining why schizophrenic symp- several psychiatric disorders. When that happens, our limbs seem to act toms are frightening to the patient. So it E COHEN independently of us. seems we know that our limbs belong to us M BERNARDO Research2 conducted in the 1980s has because they obey us. When they seem to J MASANA found that the same electrical brain wave stop responding to our wills, we conclude that FJARRUFAT changes that characteristically precede all our limbs are no longer our own, and try to V NAVARRO limb movements, occur several 100 ms before fend them oV. Hence it would seem that one Department of Psychiatry we seem to consciously decide to move a of the prices we had to pay for conscious J VALLS-SOLÉ limb. If our conscious decision to act is awareness of ourselves to evolve as a function Department of Neurophysiology preceded by brain changes that anticipate of the brain, is the delusion that we are T BOGET action, then our “decision” to choose how to responsible for all our actions. If we had con- N BARRANTES behave or “freedom”, as in free will, is in fact scious awareness of ourselves, but no sense of S CATARINEU illusory. Our choices have in a sense been free will, our bodies would feel alien to us. M FONT decided beforehand by our brains. The philosophical importance of alien hand Department of Psychology Spence3 asserts that evidence such as this, syndrome is that it shows emphatically via F J LOMEÑA combined with phenomena such as alien neurology that it is possible to drive a wedge Department of Nuclear Medicine, hand syndrome, means that philosophers between consciousness and the experience of Institut d’ Investigacions Biomédiques August Pi i have to reconsider whether we have free will. free will. The brain had to develop the sensa- Sunyer, Hospital Clínic i Provincial. Universitat de tion of free will after developing conscious- He argues that these data suggest that our Barcelona, Spain ness, because being without the sensation of sense of agency is illusory and it follows that free will produces extremely negative emo- Correspondence to: Dr M Bernardo, Servicio de most of us share in common the useful delu- Psiquiatría, Hospital Clínic i Provincial, Villarroel tional experiences. So the fact that every case sion that we have free will. Patients with alien 170, 08036 Barcelona, Spain. Telephone 00343 so far reported of alien hand syndrome hand syndrome have lost this experience in 2275400, ext 2405; fax 00 343 2275477; email imputes negative intent to the alien limb relation to a particular limb. There is a sense [email protected] might not be an incidental finding, but a core then that those who experience the syndrome aspect of the disorder. are closer to the reality of how much we are 1 Barker AT, Jalinous R, Freeston IL. Non- responsible for our actions than the rest of us. R PERSAUD invasive magnetic stimulation of the human This is because they have lost the function of The Maudsley Hospital, Croydon Mental Health motor cortex. Lancet 1985;i:1106–7. Services, Westways Rehabilitation Unit, 49 St James’s 2 George MS, Wassermann EM. Rapid-rate tran- the part of the brain that normally works to Road, West Croydon, Surrey CR9 2RR, UK. Telephone scranial magnetic stimulation and ECT. Con- make us think that we have conscious 0044 181 700 8512; fax 0044 181 700 8504; email vuls Ther 1994;10:251–4. freedom of will. They develop the experience, 3 Pascual-Leone A, Catala MD, Pascual-Leone [email protected] AP. Lateralized eVect of RTMS on the prefron- therefore, of becoming mere remote specta- tal cortex on mood. Neurology 1996;46:499– tors to the actions of their bodies. 502. Defenders of human “free will” argue what 1 Ay H, Buonanno FS, Price BH, et al. Sensory 4 Elliot R, Sahakian B. The neuropsychology of alien hand syndrome: case report and review of schizophrenia: relations with clinical and neu- happens before the brain itself decides to act is still unknown, and there may be a role for the literature. J Neurol Neursurg Psychiatry robiological dimensions. Psychol Med 1995;25: 1998;65:366–9. 581–94. our own autonomy there. But even these free 2 Libet B, Gleason CA, Wright EW. Time of con- 5 Wolkin A, Sanfilipo M, Wolf AP, et al. Negative will guardians concede the neurological scious intention to act in relations to onset of symptoms and hypofrontality in chronic research indicates that whatever happens cerebral activity: readiness-potential. Brain schizophrenia. Arch Gen Psychiatry 1992;49: 1983;106:623–42. 959–65. before the brain is roused, must occur below 3 Spence SA. Free will in the light of neuropsy- 6 Lingjaerde O, Ahlfors UG, Bech P, et al. The our conscious awareness. chiatry. Philosophy Psychol Psychiatry 1996;3: UKU side eVects scale. Acta Psychiatr Scand Yet in alien hand syndrome the patient 75–90. 1987;76(suppl 334):1–100. thinks that the hand has hostile motivations; 4 Crow TJ. Schizophrenia as a transcallosal misconnection syndrome. Schizophr Res 1998; it is invariably the case that the patient not 30:111–4. only thinks that the limb is “not self” but finds that the limb behaves towards the self in a destructive and aggressive manner. This The authors reply: CORRESPONDENCE could be explained by the suggestion that if We appreciate Persaud’s comments regarding we lose our conscious sense of voluntary con- the alien hand syndrome, “the perceived trol over our bodies, our minds have to come malevolence of the aVected limb towards its up with an explanation for the location of victim, and the question of whether with loss action of our movements. We decide that if of the conscious sense of voluntary control Sensory alien hand syndrome ourselves are not in control, then someone or over our bodies, our minds... decide that if something else must be; therefore, we no ourselves are not in control then someone or The case report by Ay et al1 of alien hand syn- longer have a sense of the limb belonging to something else must be”. We would oVer that drome and review of the literature neglected us. the value of our particular case is that it was the intriguing issue of why in every case so far Because to lose control over our bodies is due to a central deaVerentation—therefore reported the patient seems to be terrified of one of the most terrifying experiences, our the term “sensory alien hand syndrome”. As