Dear Editor,

The use of sympathicomimetic agents for the study of palpebral ptosis has been known for years (1). In ophthalmology we use them asidually to measure the potential effectivity of a müllerectomy as a therapeutic procedure in many different types of palpebral ptosis, being phenylephrine in various concentrations (ranging from 2,5% to 10%) the most commonly used (2). But despite being useful in proving Müller-muscle activity, a positive response to sympathicomimetic agents does not allow us to do an accurate differential diagnosis between myogenic and neuropathic ptosis. The use of adrenergic agents for the diagnosis of dysfunctions of the sympathetic nervous system has been extended since the reports by Morales et al (3)with the use of apraclonidine for the diagnosis of Horner’s syndrome. Though having a major alfa-2-adrenergic effect, apraclonidine's weak alfa-1 adrenergic effect can be used to evaluate denervation supersensitivity of the affected pupil, which when dilated would produce a reversal of the previous anisocoria. The use of apraclonidine for the diagnosis of Horner's syndrome has been postulated as a possible substitute of the classic cocaine test (4). We described the palpebral effect of apraclonidine 2 years ago, showing also a lid supersensitivity response in the affected eye after bilateral instillation and have even considered the possiblity of using apraclonidine as a therapeutic agent in patients who are reluctant to undergo eyelid surgery (5).

We believe your study present certain limitations: 1. A positive response to naphazoline instilation does not exclude miopathic causes of palpebral ptosis, since elevation of the eyelid is not restricted to Horner’s syndrome. This effect has also been described in other causes of ptosis, not only in those secondary to ympathetic dysfunction (6). 2. Maybe it would be more useful, as in with the use of apraclonidine, to consider both pupils' response, evaluating the possibility of a positive pupillary response due to denervation in the pathologic eye. It is possible that naphazoline’s highly selective alfa-2-adrenergic action does not allow an apropriate differential diagnosis and this possibility would need to be confirmed through a study comparing naphazoline with cocaine drops (less response of the pathologic pupil) and with apraclonidine (reversal of the anysocoria). We could find, as with phenylephrine, that it is only partially useful in differentiating between 2nd and 3rd order neuron, but not useful in confirming Horner’s syndrome(7). 3.Unilateral instilation, as detailed in the article, causes the limitation of not evaluating a simultaneous response in both pupils and eyelids, and therefore we consider that instilation should be done in both eyes, evaluating the bilateral response and establish the presence or absence of a positive response secondary to denervation. In your second case, you obtain a left pupillary mydriatic response after unilateral instillation of nafazoline, with the limitation of not being able to compare this with the other eye’s response.

REFERENCES

(1)Perry JD, Kadakia A, Foster J. A New Algorithm for Ptosis Repair Using Conjunctival Mullerectomy With or Without Tarsectomy. Ophthal Plast Reconstr Surg 2002, 18 :426-429.

(2)Martin PA, Rogers PA. Involutional ptosis: recognition and management. Aust N Z L Ophthalmol 1985 ;13(2):185-7

(3)Morales J, Brown SM, Abdul-Rahim AS, Crosson CE. Ocular effects of apraclonidine in Horner syndrome. Arch Ophthalmol 2000; 118 (7): 951-4.

(4)Kardon R. Are we ready to replace cocaine with apraclonidine in the pharmacology diagnosis of Horner syndrome? . J Neuroophthalmol 2005; 25(2):69-70

(5)Sánchez-Dalmau B, Romero B, Burés A, Vela MD, Adan A. Apraclonidine 0.5% in the treatment of ptosis in Horner’s syndrome. Presented as Poster in the 32nd Annual NANOS (North-American Neuroophthalmology Society) Meeting. Tucson. Feb-March 2006.

(6)Uncini A, De Nicola G, Di Muzio A, Rancitelli G, Colangelo L, Gambi D, Gallenga PE. Topical naphazoline in the treatment of myopathic ptosis. Acta Neurol Scand 1993; 87(4):322-4

(7)Danesh-Meyer HV, Savino P, Sergott R. The correlation of phenylephrine 1 % with hydroyamphetamine 1 % in Horner’s syndrome. Br J Ophthalmol 2004, 88(4): 592-3.

Dear Editor,

In the wake of the paper by Young et al. (1), Professor Goadsby addresses the mysteries of migraine (2). Migraine has become enveloped in an existential debate; its very origin is under intense scrutiny (3,4). A year ago, I raised the issue of unaddressed but vitally important components of the Gordian knot of migraine (4). I have also previously underscored the conceptual limitations imposed by an over-elaborate classification system (IHS, 2004) that has no pathophysiological basis and that impedes the creation of an overarching theory or unifying hypothesis for primary vascular headaches. In attempting to define the limits of our comprehension of migraine, Goadsby’s critique (2) does not grapple with any one of fifteen key questions that I have outlined and that cannot be circumvented by clinical trials or animal experiments or meta-analyses or mathematical statistics.

Researchers invariably try to bring the research community around to their own viewpoint(s); in this context, it apparently becomes important to set the terms as well as the limits of the debate. Migraine is a classic example of serendipity in medical science and therapeutics: a long, winding, completely unchartered road stretches from beta-blockers to closure of patent foramen ovale to scalp injection of botulinum toxin with the frontiers of therapeutic deep brain stimulation looming in the not-too -distant future. In contrast to serendipity in infective disorders such as helicobacter pylori-related peptic ulceration/dyspepsia with instantaneous and profound therapeutic benefits, serendipity in non-infective disorders can extract heavy costs in terms of missed opportunities and delayed comprehension of disease mechanisms for both patients and therapists (5). As if serendipity was not enough, a clumsy entirely-subjective nosological system designed by authoritative consensus amongst neurologists and adapted uncritically by most researchers dominates the thinking of primary vascular headache researchers. Nevertheless, there is not one recorded case of expanding (‘marching’) scintillating scotoma in the nasal visual field; the theoretical compulsion for neurologists to sustain the belief for a primary pathogenetic involvement of the occipital cortex has little if any basis (3,4). Hemianopic is not the same as homonymous hemianopic distribution, a neuro-ophthalmic clinical reality well-understood but ignored by neurologists immersed in migraine research (6). Finally, while atenolol does not modulate any brain function critically but prevents both migraine with aura and migraine without aura equally well, magnesium does not freely cross the blood-brain-barrier (BBB) and attenuates augmented BBB permeability (5). The magnitude of the opportunity and the challenge that migraine presents is indeed tremendous, but to conclude, as Goadsby does (2) that migraine is a disorder of the brain is a forceful reiteration that appears fatally wounded by clinico-phamacological realities. What might be conceded at this stage is that the belief that “Migraine is a disorder of the brain” is a carefully structured medical myth (5). Also, to the extent we allow our expectations to shape our findings and interpretations – yes, migraine is indeed a disorder of the brain.

Clear neuro-psychiatric guidelines exist for labeling patients as “crazy” or “malingering”. While no suggestion has been made to label MUMS patients in either category (3) or in the category of “modified madness” that Goadsby suggests, the semantic and scientific controversy stems from our desire to pigeonhole patient behaviour into known neuro-paralytic or non-paralytic paradigms. That disordered sensory attentional mechanism is a fundamental feature of migraine is far from proven and to extrapolate even further that MUMS is possibly a motor complication of disordered attention, as Goadsby does (2), is to stray even further in the realm of speculation. Allodynia has been misconstrued in migraine research (5,7), ostensibly to give clinical meaning to the entity of chronic migraine as well as to justify prophylactic use of triptans (in itself, if successful, a gigantic marketing coup). To project an aberrant clinical parameter / behaviour in a minority of patients to the pathophysiology of a disorder as complex (more correctly, as poorly understood) as migraine does not seem to be a progressive step.

While Goadsby’s studentship (2) can only be envied, five remarkable traits of great minds bear mention: to delight in what seems inconsequential, to welcome questions that challenge extant premises, to maintain a broad overview, to acknowledge error with consummate grace, and to be willing to swim against the current. Probing questions that do not let the mind rest (?rust) in peace are stepping stones to discovery, both medical and non-medical.

References:

1. Young WB, Gangal KS, Aponte R, Kaiser RS. Migraine with unilateral motor symptoms (MUMS): A case control study. J Neurol Neurosurg Psychiatry published online 20 October 2006, doi: 10.1136/jnnp.2006.100214.

2. Goadsby PJ. MUMS the word – Migraine with unilateral motor symptoms – what can you say? J Neurol Neurosurg Psychiatry published online 21 Feb 2007; doi:10.1136/jnnp.2006.108449.

3. Gupta VK. Migraine and unilateral giveway motor weakness: atypical, pseudo-paretic behavioural epiphenomenon. J Neurol Neurosurg Psychiatry published online 27 October 2006. Available at: http://jnnp.bmj.com/cgi/eletters/jnnp.2006.100214v1#1160.

4. Gupta VK. Migraine: “how” versus “what” of a disease peocess. BMJ published online 8 February 2006; available at: htpp://www.bmj.com/cgi/eletters/332/7532/25/25#127734.

5. Gupta VK. Adaptive mechanisms in migraine: a critical conceptual hiatus. In: Migraine Disorder Research Trends. New York: Nova Scientific Publishers, 2007.

6. Gupta VK. Monocular and “binocular” scintillating scotomata in migraine: a semantic and theoretical paradox. CMAJ published online 23 November 2006. Available at: http://www.cmaj.ca/cgi/eletters/173/12/1441.

7. Gupta VK. Pre-emptive / early intervention with triptans in migraine: hope, hype, and hazard. Int J Clin Pract 2007;61:350-352.

Vinod K Gupta

Dear Editor,

Precisely 80 years have elapsed since G. Elliot Smith presented a review of "Die Cytoarchitektonik der Hirnrinde des erwachsenen Menschen" by Professor Constantin Von Economo and Georg N. Koskinas in the Journal of Anatomy {1}. As one can read in this review the book included 162 partly-coloured text figures and an atlas of 112 micro-photographic tables and it was edited by Julius Springer, it's price being 600 marks. The reviewer denotes that " the authors have brought to their work not merely superb technical skill and enormous patience, but they have dealt with the history and the literature of the subject with rare judgment and impartiality, and in particular a freedom from national bias". According to him "such a survey will not have to be done again, and this work will become a standard treatise of reference on the topography of the human cerebral cortex. No doubt in the future much detailed work will be done upon particular regions, perhaps introducing small points of modification, but the work as a whole is bound to stand as a permanent achievement"....and he concludes his review writing " All that I need say further is that the authors and the publisher deserve the real thanks of anatomists, for having provided so eminently trustworthy a book of reference to a subject the literature of which is rapidly getting out of hand".

References

1. Smith GE:Die Cytoarchitektonik der Hirnrinde des erwachsenen Menschen. J Anat. 1927 Jan; 61(Pt 2): 264-266

Dear Editor,

I have read the article (1) with interest and found it to be very useful for managing the Parkinson’s disease. In this context I would like to mention few things. In spite of advances in therapy of Parkinson’s disease, gait and balance deficits are the major problems causing loss of independence. More recently multi disciplinary neuro rehabilitation treatments have been proposed to treat Parkinson’s disease sequel. BenSidaway et al (2) have shown that one month gait training with visual cues was successful in establishing a lasting improvement in gait speed and length. Protas E J etal (3) found that gait and step training resulted in a reduction in falls and improvement in gait and dynamic balance. Gwyn N et al (4) suggested that improvement in Parkinson’s disease gait pattern with the use of visual cues may arise through the patient’s ability to use visual feedback to regulate movement amplitude, reducing their kinesthetic feedback. The present study is the largest study on gait training in Parkinson’s disease and also training, testing done at home environment. Suteerawattananon M et al (5) have shown in their study that both auditory and visual cues improved the gait performance, the former improves the cadence, while the latter improves the stride length, simultaneous use of both cues did not improve gait significantly more than each cues alone. In the present study, (1) with both visual and auditory cues there was a significant increase in walking speed and step amplitude, with a tendency to reduce step frequency. If the authors (1) had noted if there was any difference in gait velocities and step length between the two cues in this trial then it would have shown a new insight regarding which of the two cues is better, so as to develop a cuing device at a lower cost.

Secondly, in this trial the cueing training period is only for a short period. Fitts P M. (6) proposed that people pass through three stages while acquiring new skills. The first stage ,during which the persons understands the requirement of the task, in the second stage, the fixation stage, specific requirements like speed, amplitude and force are refined through large amounts of practice. In the third stage, automatic phase, motor skill is well established and can be performed automatically with limited demands on attentional mechanism. Meg E Morris et al (7), in their study found that patients with Parkinson’s disease are in second stage of motor skill acquisition and preferred gait pattern had not yet become automatic due to insufficient training and also stated that visual cues training enhanced stride length in Parkinson’s disease by focusing attention on the criterion step size. So a prolonged period of gait training may be required to have some retention effect of training and to become automatic. In a study by Seitz et al (8) provide some indication that basal ganglion play a primary role in allowing movement performance to shift from conscious control to automaticity. In the present study the gait related attention also can not be ruled out, and may be a factor for training effects were not sustained at 6 weeks follow up. So further studies using longer periods of training with cues are needed to see whether the preferred gait parameters increase and become automatic with prolonged periods of training and the impact of visual cues vs. auditory cues in gait parameters to find out the better one, so as to develop a cueing device at a lower cost with better results.

In the present trial the authors (1) have excluded the patients who have undergone D.B.S. In a recent study W,M.M.Schupbach et al (9), patients with early stage of Parkinson’s disease having D.B.S shown to improve in their quality of life. However long terms follow up in patients undergoing DBS are few. In a Multicenter trial M.C.Rodrogues-Oroz et al (10) assessing the long term efficacy of either STN or Gpi stimulation, a significant and substantial clinically improvement for at least 3-4 years. So if in the present study (1), patients already having DBS been included, it could have shed some lights on the effect of cuing training in patients having DBS, so as to see any additive effects in improvement in gait parameters. In conclusion, the study by A Nieuwboer et al (1) is a very useful study and shed a light for rehabilitation therapy at home environment for Parkinson’s disease with good results and future direction.

Sandip Kumar Dash

References

1. A Nieuwboer,G Kwarkkel,L Rochester,D Jones,E van Wegen, A MWillems,F Chavret,V Hetherington,K Baker,I Lim.—Cueing training In the home improves gait-related mobility in Parkinson’s disease: RESCUE trial. J Neurol.Neurosurg Psychiatry, 2007, 78,134-140.

2. Ben Sidaway,Jennifer Anderson,Garth Danielson,Lucas Martin ,Garth Smith.—Effects of Longterm gait training using visual cues in an individual with Parkinson’s disease.—Phys Ther,2006,vol.86 ,2,feb,186-194.Abstract.

3. Protas EJ,Mitchell K,Williams A, Quereshy H,Caroline k,Lai E C.—Gait and step training to reduce falls in Parkinson’s disease.-NeuroRehabilitation, 2005, 20, (3):183-90Abstract.

4. Gwyn N.Lewis,Winston D.Byblow,Sharon E.Walt.—Stride length regulation in Parkinson’s disease; the use of extrinsic ,visual cues.-Brain,2000,123,2077-209.

5. Suteerawattananon, M, Morris G S, Etnyre BR, Jancovic j, Protas EJ.—Effects of visual and auditory cues on gait in individuals with Parkinson’s disease,--J Neurol Sci. 2004, April 15,219(1-2):63-69.Abstract.

6. Fitts PM.-Perceptual motor skills learning in: Melton AW, Editor. Categories of human learning. New York: Academic Press, 1964, 243-85.Crossref.

7. Meg E Morris,Robert Lansek,Thomas A Matyas,Jeffery JSummers.—Stride length regulation in Parkinson’s disease Normalization strategies and underlying mechanisms.-Brain,1996,119,551-568.

8. Seitz R J,Roland PE.-Learning of sequential finger movements in man: a combined kinematics and positron emission tomography(PET)study.Eur J Neurosci,1992,4:154-165.Crossref.

9. W M M .Schupbach,D Maltete,J L Houet,S Tezenas du Montcel,L Mallet,M LWelter,M Gargiulo,C Behar,A M Bonnet,V Czernecki,B Pidoux,S Navarro,D Dormont,P Cornu,Y Agid—Neurosurgery at an earlier stage of Parkinson’s disease,Neurology,2007,68,267-271.Abstract.

10. M C Rodriguez-Oroz,J A Obeso,A E Lang,J L Houeto,P Pollak et al-Bilateral deep brain stimulation in Parkinson’s disease, a multicentre study with 4 years follow up, Brain, 2005, 128, (10) :2240-2249.