Recent eLetters

We read with great interest a recent article by Morgante et al1 concerning the prevalence of psychosis associated with Parkinson disease. Psychotic symptoms, mainly visual hallucinations (VHs), occur in about one -third of patients, and thought to be a complication of antiparkinsonian treatment. However, they reported that psychotic type symptoms of PD, such as VHs, might occur more frequently in the early stage compared with later stages. In population-based, case-control study, PD patients historical records were examined for depression and anxiety in pre-motor phase of PD.2-4 Notably, Shiba et al3 described that the association with anxiety was significant even when the analysis went as far back as 20 years before the onset of motor symptoms.3 These studies show that anxiety and depression are associated with PD and suggest that the causative process or risk factors underlying PD may be present many years before motor symptoms onset. Neither the mechanism of VHs nor frequency of VHs in pre-motor phase are not clear in PD. One potential explanation for VHs is the imbalance with cholinergic neurotransmission rather than dopaminergic overactivity due to antiparkinsonian treatment. Loss of dopaminergic nigrostriatal function occurs before motor symptoms onset in PD and influences the serotonergic, noradrenergic and cholinergic systems. We suspect that imbalance of cholinergic system induces the VHs in the early motor stage of PD. The beneficial effect of cholinesterase inhibitor on VHs supports our suggestion.5

REFERENCES 1. Morgante L, Colosimo C, Antonini A, et al. Psychosis associated to Parkinson's disease in the early stages: relevance of cognitive decline and depression. J Neurol Neurosurg Psychiatry 2012;83:76-82. 2. Alonso A, Rodriguez LA, Logroscino G, et al. Use of antidepressants and the risk of Parkinson's disease: a prospective study. J Neurol Neurosurg Psychiatry 2009;80:671-4. 3. Shiba M, Bower JH, Maraganore DM, et al. Anxiety disorders and depressive disorders preceding Parkinson's disease: a case-control study. Mov Disord 2000;15:669-77. 4. Weisskoph MG, Chen H, Schwarzschild MA, et al. Prospective study of phobic anxiety and risk of Parkinson's disease. Mov Disord 2003;18:646-51. 5. Kurita A, Ochiai Y, Kono Y, et al. The beneficial effect of donepezil on visual hallucinations in three patients with Parkinson's disease. J Geriatr Psychiatry Neurol 2003;16:184-8.

Conflict of Interest:

None declared

Dear Editors,

The dorsal horns are not merely passive transmission stations but sites at which dynamic activities (inhibition, excitation and modulation) occur. [18]

Via a series of filters and amplifiers, the nociceptive message is integrated and analysed in the cerebral cortex, with interconnections with various areas. [1]

The processing of pain takes place in an integrated matrix throughout the neuroaxis and occurs on at least three levels, at peripheral, spinal, and supraspinal sites. [9]

Knowledge of the modalities of pain control is essential to correctly adapt treatment strategies (drugs, neurostimulation, psycho-behavioural therapy, etc.).

Dysfunction of pain control systems causes neuropathic pain. [1]

Spinal Cord Stimulation modalities evolved from the gate-control theory postulating a spinal modulation of noxious inflow. [16] [2] [7] [11] [12] [15] [17] [20] [22] [23] [24] [25] [26]

It has been demonstrated in multiple studies that dorsal horn neuronal activity caused by peripheral noxious stimuli could be inhibited by concomitant stimulation of the dorsal columns. [8]

Pain relief was more prominent at pain ascending through C fibers than pain ascending through Adelta fibers [21]

Many theories on the mechanism of action of Spinal Cord Stimulation have been suggested, including activation of gate control mechanisms, conductance blockade of the spinothalamic tracts, activation of supraspinal mechanisms, blockade of supraspinal sympathetic mechanisms, and activation or release of putative neuromodulators. [14]

At present, Spinal Cord Stimulation is a well established form of treatment for failed back surgery syndrome, complex regional pain syndromes (CRPS), low back pain with radiculopathy and refractory pain due to ischemia. [4] [3] [8] [13]

Stimulation produced analgesia can provide a level of analgesia and efficacy that is unattainable by other treatment modalities. [19]

Spinal Cord Stimulation for the treatment of chronic pain is cost- effective when used in the context of a pain treatment continuum. [14]

Precise subcutaneous field stimulation is targeted to specific areas of neuropathic pain. [6]

We aim at attenuation or blockade of pain through intervention at the periphery, by activation of inhibitory processes that gate pain at the spinal cord and brain. [9]

Segmental noxious stimulation produces a stronger analgesic effect than segmental innocuous stimulation. [10]

That is exactly what intradermal sterile water or subcutaneous saline injections do!

Chloride, used in subcutaneous "sham" injections, independently regulates the pain pathway. [5]

Intraspinal steroids should no longer be used since we can obtain better results using sterile water intradermal injections, especially for back pain.

Furthermore, intradermal injections are minimally invasive and absolutely NOT neurotoxic.

References

[1] Prog Urol. 2010 Nov;20(12):843-52. Epub 2010 Oct 20. Anatomy and physiology of chronic pelvic and perineal pain. Labat JJ, Robert R, Delavierre D, Sibert L, Rigaud J. Centre federatif de pelviperineologie, clinique urologique, CHU Hotel- Dieu, 1, place Alexis-Ricordeau, 44093 Nantes, France.

http://www.ncbi.nlm.nih.gov/pubmed/21056357

[2] Int J Rehabil Res. 2010 Sep;33(3):211-7. Effect of transcutaneous electrical nerve stimulation on sensation thresholds in patients with painful diabetic neuropathy: an observational study. Moharic M, Burger H. Department of Physical and Rehabilitation Medicine, Linhartova 51, SI-1000 Ljubljana, Slovenia.

http://www.ncbi.nlm.nih.gov/pubmed/20042866

[3] Conf Proc IEEE Eng Med Biol Soc. 2009;2009:2033-6. Spinal cord stimulation for complex regional pain syndrome. Shrivastav M, Musley S. Medtronic Neuromodulation, 7000 Central Ave NE, Minneapolis, Minnesota, 55432 USA.

http://www.ncbi.nlm.nih.gov/pubmed/19964771

[4] J Clin Monit Comput. 2009 Oct;23(5):333-9. Spinal cord stimulation: principles of past, present and future practice: a review. Kunnumpurath S, Srinivasagopalan R, Vadivelu N. St George's School of Anaesthesia, Tooting, London, UK.

http://www.ncbi.nlm.nih.gov/pubmed/19728120

[5] Brain Res Rev. 2009 Apr;60(1):149-70. Epub 2008 Dec 31. Chloride regulation in the pain pathway. Price TJ, Cervero F, Gold MS, Hammond DL, Prescott SA. University of Arizona, Department of Pharmacology, USA.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2903433/?tool=pubmed

[6] Curr Pain Headache Rep. 2008 Jan;12(1):28-31. Peripheral nerve stimulation for chronic pain. Henderson JM. Stereotactic and Functional Neurosurgery, Stanford University School of Medicine, 300 Pasteur Drive, Edwards Building/R-227, Stanford, CA 94305, USA.

http://www.ncbi.nlm.nih.gov/pubmed/18417020

[7] Schmerz. 2007 Aug;21(4):307-10, 312-7. From Descartes to fMRI. Pain theories and pain concepts. Handwerker HO. Institut fur Physiologie und Pathophysiologie, Universitat Erlangen/Nurnberg, Deutschland.

http://www.ncbi.nlm.nih.gov/pubmed/17674057

[8] Pain Physician. 2002 Apr;5(2):156-66. Spinal cord stimulation. Stojanovic MP, Abdi S. Interventional Pain Program, MGH Pain Center, Department of Anesthesia and Critical Care, Massachusetts General Hospital, Harvard Medical School, Cambridge, MA 02135, USA.

http://www.ncbi.nlm.nih.gov/pubmed/16902666

[9] J Bone Joint Surg Am. 2006 Apr;88 Suppl 2:58-62. Basic science of pain. DeLeo JA. Dartmouth-Hitchcock Medical Center, Dartmouth Medical School, Neuroscience Center at Dartmouth, Department of Anesthesiology, Lebanon, NH 03756, USA.

http://www.ncbi.nlm.nih.gov/pubmed/16595445

[10] Pain. 2005 May;115(1-2):152-60. Segmental noxious versus innocuous electrical stimulation for chronic pain relief and the effect of fading sensation during treatment. Defrin R, Ariel E, Peretz C. Department of Physical Therapy, School of Allied Health Professions, Sackler Faculty of Medicine, Tel-Aviv University, 69978 Ramat Aviv, Israel.

http://www.ncbi.nlm.nih.gov/pubmed/15836978

[11] Annu Rev Neurosci. 2003;26:1-30. Epub 2003 Mar 6. Pain mechanisms: labeled lines versus convergence in central processing. Craig AD. Atkinson Pain Research Laboratory, Barrow Neurological Institute, 350 W.Thomas Road, Phoenix, AZ 85013, USA.

http://www.ncbi.nlm.nih.gov/pubmed/12651967

[12] Sports Med. 2002;32(4):251-67. Return-to-work interventions for low back pain: a descriptive review of contents and concepts of working mechanisms. Staal JB, Hlobil H, van Tulder MW, K?ke AJ, Smid T, van Mechelen W. Department of Social Medicine and Research Centre on Work, Physical Activity and Health, VU University Medical Center, Van der Boechorststraat 7, Amsterdam, The Netherlands.

http://www.ncbi.nlm.nih.gov/pubmed/11929354

[13] Curr Pain Headache Rep. 2001 Apr;5(2):130-7. Stimulation methods for neuropathic pain control. Stojanovic MP. MGH Pain Center, Department of Anesthesia and Critical Care, Massachusetts General Hospital, Boston, MA 02114, USA.

http://www.ncbi.nlm.nih.gov/pubmed/11252147

[14] Curr Rev Pain. 1999;3(6):419-426. Spinal Cord Stimulation: Indications, Mechanism of Action, and Efficacy. Krames E. Pacific Pain Treatment Centers, 2000 Van Ness Avenue, Suite 402, San Francisco, CA 94109, USA.

http://www.ncbi.nlm.nih.gov/pubmed/10998699

[15] Ann Pharm Fr. 2000 Mar;58(2):77-83. Pain and its main transmitters. Costentin J. Unite de Neuropsychopharmacologie Experimentale, ESA 6036 CNRS, Institut Federatif de Recherches Multidisciplinaires sur les Peptides=IFR 23, Faculte de Medecine et Pharmacie, 22, bd Gambetta, F 76000 Rouen.

http://www.ncbi.nlm.nih.gov/pubmed/10790600

[16] Neurol Res. 2000 Apr;22(3):285-92. Mechanisms of spinal cord stimulation in neuropathic pain. Meyerson BA, Linderoth B. Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.

http://www.ncbi.nlm.nih.gov/pubmed/10769822

[17] Pain. 1999 Aug;Suppl 6:S149-52. Regulation of spinal nociceptive processing: where we went when we wandered onto the path marked by the gate. Yaksh TL. Department of Anesthesiology, University of California, San Diego, USA.

http://www.ncbi.nlm.nih.gov/pubmed/10491984

[18] Pain. 1999 Aug;Suppl 6:S121-6. From the gate to the neuromatrix. Melzack R. Department of Psychology, McGill University, Montreal, Quebec, Canada.

http://www.ncbi.nlm.nih.gov/pubmed/10491980

[19] J Clin Neurophysiol. 1997 Jan;14(1):46-62. Stimulation of the central and peripheral nervous system for the control of pain. Stanton-Hicks M, Salamon J. Anaesthesia Pain Management Center, Cleveland Clinic Foundation, OH 44195, USA.

http://www.ncbi.nlm.nih.gov/pubmed/9013359

[20] Percept Psychophys. 1996 Jul;58(5):693-703. An investigation of the gate control theory of pain using the experimental pain stimulus of potassium iontophoresis. Humphries SA, Johnson MH, Long NR. Department of Psychology, Massey University, Palmerston North, New Zealand.

http://www.ncbi.nlm.nih.gov/pubmed/8710448

[21] J Peripher Nerv Syst. 1996;1(3):189-98. Pain relief by various kinds of interference stimulation applied to the peripheral skin in humans: pain-related brain potentials following CO2 laser stimulation. Kakigi R, Watanabe S. Department of Integrative Physiology, National Institute for Physiological Sciences, Okazaki, Japan.

http://www.ncbi.nlm.nih.gov/pubmed/10970109

[22] Nurs Stand. 1993 Jul 28-Aug 3;7(45):25-7. Pain: opening up the gate control theory. Davis P.

http://www.ncbi.nlm.nih.gov/pubmed/8398721

[23] Bull Acad Natl Med. 1989 Oct;173(7):855-60; discussion 860-1. Gate control of the nociceptive message: applications to the treatment of pain. Cambier J.

http://www.ncbi.nlm.nih.gov/pubmed/2620243

[24] Brain Res. 1983 Dec 5;280(2):217-31. Thalamic nucleus ventro-postero-lateralis inhibits nucleus parafascicularis response to noxious stimuli through a non-opioid pathway. Benabid AL, Henriksen SJ, McGinty JF, Bloom FE.

http://www.ncbi.nlm.nih.gov/pubmed/6652483

[25] Psychosom Med. 1979 Mar;41(2):101-8. A signal detection analysis of the effects of transcutaneous stimulation on pain. Malow RM, Dougher MJ.

http://www.ncbi.nlm.nih.gov/pubmed/441227

[26] GATE CONTROL OF ION FLUX IN AXONS. GOLDMAN DE. J Gen Physiol. 1965 May;48:SUPPL:75-7.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2213778/pdf/75.pdf

Conflict of Interest:

None declared

We are concerned that the article by Professor Swash [1] misrepresents both the nature and findings of our recent UK national survey of the use of NIV in patients with MND/ALS. Although entitled an "editorial commentary", the article is essentially restricted to a critique of our study alone. In particular, he criticises the response rate to the survey (63%) and the lack of verification of the data in a sub -population; he grudgingly acknowledges that the study "contains some hints of changing practice" but concludes that "it would be unwise to place too much reliance on these suggestions." Most of the criticisms have already been refuted or acknowledged in our paper. In the light of recent evidence showing the benefits of NIV in this population,[2-4] the main aim of the survey was to compare present practice with that found in a virtually identical survey we performed 9 years earlier.[5] To ensure comparability between the two surveys, we used the same methodology; questionnaires were posted to all practising neurologists in the UK, identified through the Association of British Neurologists, with a second mailing to non-respondents. In this respect, ours is a more complete survey of national practice than others, which have largely been limited to specific regions, specialist centres or neurologists who elected to participate. The number of new cases of MND diagnosed in the preceding year was virtually identical in our two surveys, reflecting the relatively stable incidence of MND, and in line with the expected incidence in the UK. This implies that most of the neurologists involved in the care of MND patients responded. In the paper, we acknowledged that, as with most such surveys, the data were not independently verified in a sub-group of neurologists; it should be noted that the survey was anonymous and most of the information collected reflects aspects of practice that could not have been gleaned from a database. Where specific numbers of patients were requested, the scope for error is much smaller than suggested by Swash as, in MND, NIV is initiated only after careful consideration, the number referred by individual neurologists is small and any individual errors are mitigated by the large number of responses. Our results showed a very large increase in the number of patients referred for, and successfully initiated on, NIV (2.6 and 3.4 fold respectively), as well as other improvements in respiratory care. These impressive increases over a short period are much greater than any potential reporting error by individual neurologists. With regard to data on quality of life (QoL), the author seems to have misunderstood the purpose of our study, which was a large-scale survey of national practice rather than a study of the benefits of treatment. We have previously shown that NIV improves the QoL of patients with MND;[3] clearly, it was not our aim to show this again, nor would it have been feasible to gather QoL data on a representative cohort of patients in the practice of each neurologist. We acknowledge that we did not compare the practice of individual neurologists to national guidelines. We highlight that the National Institute of Clinical Excellence (NICE) guidelines,[6] were in development, but they were not available over the time period to which the survey referred. Judging the practice of neurologists against these guidelines would clearly have been inappropriate. We would suggest that our approach provided much more worthwhile information: we assessed the actual practice of each neurologist, including whether referral for NIV was based on symptoms alone or in combination with physiological impairment, whether they consider early intervention (physiological impairment with no or only minimal symptoms) and, if respiratory function was assessed, which specific tests were applied, whether they were performed at presentation, routinely or only if symptomatic, and the specific threshold that triggered referral. We showed that, compared to the main body of neurologists, those with the highest rates of referral for NIV were more likely to monitor respiratory function routinely and (in addition to vital capacity) they were more likely to measure sniff nasal inspiratory pressure and arterial blood gases and to consider early intervention. Assessment along these lines is supported by the recently published National Institute of Clinical Excellence guidelines. Swash interprets our analysis by practice size incorrectly. We ranked the size of neurologists' practice in quartiles according to the number of new patients seen. Compared to neurologists in the quartile with the largest practice, those with practices in the lowest quartile had a similar NIV referral rate (corrected for practice size), but the proportion of patients successfully established on NIV was lower (an outcome of importance to patients and their carers). Also, we found that neurologists within the lowest practice quartile were less likely to monitor respiratory function and less likely to rely on the combination of symptoms and respiratory function, both factors likely to influence appropriate selection of patients for NIV.

With regard to oxygen therapy, the potential for varying interpretation of the commonly used phrase "end of life" is covered in our paper. Neurologists were asked about their use of oxygen 1) at the end of life, 2) prior to the end of life, NIV not tolerated / inappropriate and 3) prior to the end of life, before a trial of NIV. We think this is clear. We only highlighted the use of oxygen in the latter group (26% of responding neurologists). The humane and reasonable use of oxygen to which Swash refers applies to the former two groups (full data shown in our paper, Table 6). Whilst it is well documented that patients with hypercapnia due to respiratory muscle weakness share the propensity of others with hypercapnia to develop more severe and potentially life- threatening carbon dioxide retention when breathing uncontrolled oxygen, our experience, and now the results of our survey, suggest that this is not widely recognised by clinicians.

References

1. Swash M. Survey of non-invasive ventilation use in ALS in Britain. J Neurol Neurosurg Psychiatry Published Online First: 2 September 2011. doi:10.1136/jnnp-2011-300990.

2. Mustfa N, Walsh E, Bryant V et al. The effect of noninvasive ventilation on ALS patients and their caregivers. Neurology 2006;66:1211- 17. 3. Bourke SC, Tomlinson M, Williams TL et al. Effects of non-invasive ventilation on survival and quality of life in patients with amyotrophic lateral sclerosis: A randomised controlled trial. Lancet Neurology 2006;5:140-47.

4. Farrero E, Prats E, Povedano M et al. Survival in amyotrophic lateral sclerosis with home mechanical ventilation: The impact of systematic respiratory assessment and bulbar involvement. Chest 2005;127:2132-38.

5. Bourke SC, Williams TL, Bullock RE et al. Non-invasive ventilation in motor neuron disease: Current UK practice. Amotroph Lateral Scler Other Motor Neuron Disord 2002;3:145-49.

6. National Institute for Health and Clinical Excellence. Motor neurone disease - non-invasive ventilation. London: (CG105) National Institute for Health and Clinical excellence, 2010.

Conflict of Interest:

None declared

Conflict of Interest:

None declared

DR E H REYNOLDS MD FRCP FRCPsych

KING'S COLLEGE, DENMARK HILL CAMPUS WESTON EDUCATION CENTRE CUTCOMBE ROAD, LONDON SE5 9PJ Tel: 020 7848 5756 Fax: 020 7848 5530 e-mail: edward.reynolds@kcl.ac.uk

CROMWELL HOSPITAL CROMWELL ROAD, LONDON SW5 0TU Tel: 020 7460 2000 Fax: 020 7460 5555

Correspondence to: BUCKLES YEW TREE BOTTOM ROAD EPSOM DOWNS SURREY KT17 3NQ Tel: 01737 360867 Fax: 01737 363415 e-mail: reynolds@buckles.u-net.com

WERE BABYLONIANS SELF-CONSCIOUS?

We are grateful to Dr. Cavanna and Dr. Nani for their interesting and thoughtful letter on the question of Babylonian self-consciousness.

As they noted and we emphasised, Babylonian accounts of obsessive compulsive disorder, phobias and psychopathic behaviour were entirely objective. As far as we are aware accounts of the subjective phenomena in these behaviours began in the 17th century AD. The Babylonians viewed these behaviours as mysterious, yet to be explained, a reasonable view which persisted right up to the 20th century AD with all it's self- awareness.

Cavanna and Nani suggest that either the Babylonians had no concept of free will and that the behaviours were beyond the subject's will and self control, or that they lacked any self-consciousness, two rather overlapping hypotheses. In either case they ask why not blame the Gods?

Even today it is widely agreed by patients and physicians or psychiatrists alike that these abnormal behaviours are to a very large extent beyond the subject's will and control, but this in no way undermines the concept of free will in these or normal subjects. Certainly there was no word in the Babylonian language for "mind", "consciousness", and "identity", but there were words for "self" i.e. ramanu, and of course for "I" (an?ku) and "me" (i?ti). The word ramanu does not appear significantly in medical texts, but it is altogether common in the epistolary texts, for the Museums have literally hundreds of letters written between all sorts of people from different periods. Two of many examples of self-awareness include: 1) "I (Sennacherib) deliberated (the matter) on my own" (ina shitulti ramani-ia amtallik) (1); 2) "They have neglected the orders which the King gave them and are acting according to their own (orders)" (2).

As for supernatural explanations modern Assyriology has a more inclusive way of reconstructing the ancient "causation theory" of Babylonian "illness". There were wounds, injuries, fractures and falls which are to be seen as accidents, as they are today. There were "animal" causes for snake bites, scorpion stings and the worms of Helminthology. Eye diseases were brought by the wind. Convulsions and paralysis were the work of demons. The concept of "muscle" and "nerve" had not yet entered the language. Nocturnal epilepsy was brought by ghosts. For delusions of persecution the persecutors themselves were the agents; the Gods, or more accurately, the "agency" of the Gods, brought such illnesses as scurvy and tuberculosis, all fevers and many skin diseases. All of these conditions were therefore viewed as externally caused in natural or supernatural ways. In the case of the behaviours we have discussed the Babylonians were more guarded, suspecting an internal or personal cause. As we reported, they described the behaviours as if the subjects had sworn an oath, an activity which would require some degree of self-consciousness.

The suggestion that in evolutionary terms self-consciousness somehow arose in the narrow gap between the Iliad and Odyssey seems to us very dubious, not least because these classic writings were no more than stories in what is known as the age of Heros, not historical documents. It is apparent to us that the Babylonians were self-conscious, but perhaps not to the degree or level of introspection and self-awareness in more recent western civilisations, as reflected perhaps in the later appearance of the subjective in addition to the objective aspects of the behaviours we have reported.

Edward H. Reynolds1 James V. Kinnier Wilson2

1. Department of Clinical Neurosciences, King's College, London, UK. 2. Faculty of Asian and Middle Eastern Studies, University of Cambridge, Cambridge, UK.

References.

1. Luckenbill DD. Sennacherib, King of Assyria: Annals.volume 2:109 col vii, line 3. Oriental Institute Publications, University of Chicago, 1924

2. Parpola S. A letter from Shamash-shum-ukin to Esarhaddon. Iraq 1972; 34; 22, line 15.

Conflict of Interest:

None declared