To determine the effects of drugs on the progression of disease in Alzheimer’s is a major target. We read with great expectation the paper by Ellul et cols. dealing with this issue (1). In this study, the drugs prescribed to a cohort of 224 patients with Alzheimer’s were recorded at
initial assessment and then correlated with progression of the disease over the next 12-month period defined as an inc...
To determine the effects of drugs on the progression of disease in Alzheimer’s is a major target. We read with great expectation the paper by Ellul et cols. dealing with this issue (1). In this study, the drugs prescribed to a cohort of 224 patients with Alzheimer’s were recorded at
initial assessment and then correlated with progression of the disease over the next 12-month period defined as an increase of one point or more in the Global Deterioration Scale. Antipsychotics and sedatives raised the risk of increased decline(specially when taken together). On the other hand, deterioration was slowed by memantine, anticholinesterase inhibitors, statins, angiotensin converting enzyme inhibitors, and angiotensin II receptor antagonists.
The big problem with this study is not only that dosage and compliance were not considered but the fact that the neuropsychiatric condition at baseline was not considered. A huge bias might be hidden behind this point since those patients being prescribed antipsychotics and sedatives are
those whose neuropsychiatric status is worse and this is related to a higher rate progression. In fact, psychosis, agitation, and aggression are important predictors of outcome, even when the effects of medication to treat them is taken into account (2). Interestingly, a recent cohort study(3) shows that patients taking atypical antipsychotics were no more likely to decline cognitively than those who were not. On the other hand, many patients taking drugs affecting the renin–angiotensin system and statins will probably have "mixed dementia", which has a different evolution from "pure AD" (4).
Then, neither causality no association is proved by this study, and the higher rate of deterioration reported might be due to differences in the disease involving, in turn, differences in the prescribed drugs.
Manuel Menéndez
Hospital Álvarez-Buylla
References
1. J Ellul, N Archer, C M L Foy, M Poppe, H Boothby, H Nicholas, R G Brown, and S Lovestone. The effects of commonly prescribed drugs in patients with Alzheimer’s disease on the rate of deterioration. J Neurol Neurosurg Psychiatry;78:233-239
2. Lopez OL, Wisniewski SR, Becker JT, Boller F, DeKosky ST. Psychiatric medication and abnormal behavior as predictors of progression in probable Alzheimer disease. Arch Neurol;56(10):1266-72
3. Livingston G, Walker AE, Katona CL, Cooper C. Antipsychotics and cognitive decline in Alzheimer's disease: the LASER-Alzheimer's disease longitudinal study.
J Neurol Neurosurg Psychiatry. 2007;78(1):25-9
4. Bowler JV, Eliasziw M, Steenhuis R, Munoz DG, Fry R, Merskey H, Hachinski VC. Comparative evolution of Alzheimer disease, vascular dementia, and mixed dementia. Arch Neurol. 1997;54(6):697-703
I read with interest the editorial commentary on the possible causal link between cannabis consumption and stroke as reported by Mateo et al based on their short case report (Journal of Neurology Neurosurgery and
Psychiatry 2005;76:435-437).
I wish to make few comments on the purported causal relationship. Hashish is made from trichomes which are present with varying amount of surplus pla...
I read with interest the editorial commentary on the possible causal link between cannabis consumption and stroke as reported by Mateo et al based on their short case report (Journal of Neurology Neurosurgery and
Psychiatry 2005;76:435-437).
I wish to make few comments on the purported causal relationship. Hashish is made from trichomes which are present with varying amount of surplus plant material in the final product. Its manufacturing process can involve use of solvents which are used to dissolve the ‘useful’ resins.
There have also been reports of highly impure hashish products which may contain substances such as beeswax, turpentine and even other psychoactive drugs like Ketamine.
The patient described in the case report had been consuming hashish and possible contamination of the used substance cannot be ruled out and indeed this has been accepted by the authors. The possibility of a prior
cerebrovascular anomaly also cannot be ruled out. Then there is the confounding factor of alcohol which although, was not consumed in great quantity.
While presence of peripheral vascular arteritis has been described in cannabis users (Disdier P, Granel B, Serratrice J, et al. Cannabis arteritis revisited—ten new case reports) and cannabis as a cause does appear convincing in this particular case report, it will be highly premature to conclude with any certainty that cannabis is causally related to stroke. As Dr Anthony Rudd (St. Mary’s Hospital, London; BBC News) has rightly pointed out, we would have seen more such cases given the current widespread and heavy use of cannabis.
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 M...
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.
Neurology is not immune to fashion. Neuroscientists follow dictates of research fashion quite precisely like their fellow humans follow fashion in food, dress, literature, music or other trivial pursuits.
Transcranial magnetic stimulation (TMS) has gripped the imagination and the intellect of neurologists in the last few years. That TMS could possibly be effective for disorders as varied as chronic ne...
Neurology is not immune to fashion. Neuroscientists follow dictates of research fashion quite precisely like their fellow humans follow fashion in food, dress, literature, music or other trivial pursuits.
Transcranial magnetic stimulation (TMS) has gripped the imagination and the intellect of neurologists in the last few years. That TMS could possibly be effective for disorders as varied as chronic neurogenic pain
and tinnitus is in itself a red flag. Tinnitus is also associated with migraine; brain neuronal origin of the latter is under increasing scrutiny (1). That tinnitus generation and maintenance is the outcome of involvement of a broad neural network including the primary and the
associative auditory cortex (2) is an attractive theory that lacks convincing evidence.
Although no amount of evidence ever proves a hypothesis, any theory may be refuted by a single critical piece of evidence. I have an extended account of a patient with both migraine and tinnitus. A female migraine patient (now seventy-five years old) experienced prolonged and protracted attacks of tinnitus (roaring and rushing noises) only on the left side unrelated to occurrence of headache for several days or few months between 60-65 years of age; she recalled briefer episodic tinnitus previously. Most remarkably, she was able to considerably ameliorate or abort the tinnitus with self-application of pressure to the left common carotid region – a feature she discovered herself by accident. She would apply compressive pressure to the left upper and anterior side of the neck for several minutes on any one occasion. In this manner, she has obtained relief from distracting tinnitus for over a hundred times. The last episode of tinnitus was experienced about ten years previously. While she continues to experience intermittent migraine attacks, she no longer suffers tinnitus. Notably, with agitation and anxiety, the tinnitus would be aggravated suddenly and severely.
Several key aspects of tinnitus merit attention. Since tinnitus is a discontinuous intermittent sound, to buttress a neuronal origin for the clinical entity, we are required to identify a neuronal process with a matched frequency. There is no known physiological process at the level of the auditory cortex that might satisfy such a requirement. Also, the pitch of the sound experienced by different patients with tinnitus can vary and points to a modifiable rheological basis. Moreover, we would have to
concede that we truly have no definitive pharmacological measure to suppress or abort tinnitus. Finally, if tinnitus were indeed neuronal in origin, we would expect brain cortical neuronal stabilizing drugs including anti-convulsants to provide substantial relief.
Against this background, a re-organization of current perception of the basis of tinnitus is in order. I was unable to ask the patient presented herein to time the tinnitus to the pulse but such a clinical evaluation is
the surest and simplest measure to establish the source of the cochlear stimulation. Aggravation of tinnitus during agitation / anxiety also indicates a role for the cardiac stroke output. Unpredictable appearance and disappearance of tinnitus can, thus, be explained by rheological
changes in the internal carotid artery that are very likely related to a critically positioned atheromatous plaque in the internal carotid artery.
Timing of the tinnitus to the heart beat should be regarded as part of the standard evaluation of the patient with tinnitus, acute or chronic. Also, controlled compression of the common carotid region on the affected side could definitively establish the source of tinnitus. Only then will the management of tinnitus (as well as of migraine) move from “holistic’ (Aurum Manus—Golden Hands (3) and other) approaches to a scientific basis.
Interestingly, holistic is a classy in-vogue euphemism for medical myths.
Nevertheless, in patients with aggravation of tinnitus with events or circumstances that tend to prominently increase the stroke volume or cardiac output, beta-blockers might be expected to offer relief; the
negative inotropic and chronotropic action of beta-blockers coupled with their tendency to increase peripheral resistance can be expected to ameliorate tinnitus. Peripheral vasodilators such as calcium-channel
antagonists, on the contrary, might worsen such tinnitus. This important pharmacologic distinction between beta-blockers and calcium-channel antagonists is relevant to migraine management also (4).
Hyperactivity of discrete temporoparietal regions recorded by advanced neuro-imaging in patients with tinnitus (2) simply indicates activation of auditory cortical centres; it cannot (and does not) differentiate between primary and secondary cochlear or cortical activations. Neuro-imaging findings are being, unfortunately, regarded by most neurologists as indicative of primary pathogenetic process(es). Such assumptions are, however, simply untrue and misguiding. “We are all healers, and somewhere deep inside we know that anything can be healed”—while such simplistic beliefs propel the alternative medicine industry, medical science must beware of the lure of advanced technology.
Researchers must comprehend the lure and the limits of gadgets such as advanced neuro-imaging. Quite paradoxically, it is imperative for clinicians to stop “thinking through technology”.
References
1. Gupta VK. MUMS: how to bridge the gap between science and quasi-science? J Neurol Neurosurg Psychiatry (published online 28 February 2007). Available at:
http://jnnp.bmj.com/cgi/eletters/jnnp.2006.108449v1#1267
2. Rossi S, De Capua A, Ulivelli et al. Effects of repetitive transcranial magnetic stimulation on chronic tinnitus. A randomized, cross-over, double blind, placebo-controlled study. J Neurol Neurosurg Psychiatry Online First, published on February 21, 2007 as 10.1136/jnnp.2006.105007.
3. Welch R. Aurum Manus: The "Golden Hands" Method of
Crystal-based Holistic Massage Including Treatment for
Tinnitus and Migraine. Findhorn press. URL:
http://www.amazon.com/Aurum-Manus-Crystal-based-Including-
Treatment/dp/1844090868
4. Gupta VK. Silent or non-clinical infarct-like lesions in the posterior circulation territory in migraine: brain hypoperfusion or hyperperfusion? Brain 2006;129:E39. Full Text:
http://brain.oxfordjournals.org/cgi/content/full/129/1/E39?ijkey=KCcr3z28ZmDWzyw&keytype=ref
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 ov...
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.
I have read the proceedings of the Association of British
Neurologists and in particular the report of Murphy et al on Intracranial haemorrhage in the Hypereosinophilic syndrome. They claim that this has not been previously reported. This is incorrect. I had a short report
published on this topic in the JNNP in 1990, the reference is 1990; 53:440-441. I will be interested in your comments.
I have read the proceedings of the Association of British
Neurologists and in particular the report of Murphy et al on Intracranial haemorrhage in the Hypereosinophilic syndrome. They claim that this has not been previously reported. This is incorrect. I had a short report
published on this topic in the JNNP in 1990, the reference is 1990; 53:440-441. I will be interested in your comments.
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...
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
This is an interesting research about the recognition of visual memory between Parkinson¡¦s Disease Dementia (PDD) and Dementia of Lewy Body (DLB). We know much about the formed visual hallucination and visual dysfunction in shape and color in both disease entities (1-4), but not
easily elucidated the visual storage or retrieving disorder partly because of the aging and systemic factors affecting the...
This is an interesting research about the recognition of visual memory between Parkinson¡¦s Disease Dementia (PDD) and Dementia of Lewy Body (DLB). We know much about the formed visual hallucination and visual dysfunction in shape and color in both disease entities (1-4), but not
easily elucidated the visual storage or retrieving disorder partly because of the aging and systemic factors affecting the visual memory testing. Mondon et al.(5) successfully clarify the visual memory discrimination
using DMS-48 between PDD and DLB and found a significant deficit in immediate and delay recognition especially in DLB, and also found the significant decline in orientation, a subset test of Mini-Mental State
Examination (MMSE) and prolonged the time in Trail Making Test-A (TMT-A) (p<0.05).
As most researches do, the whole neuropsychological tests are difficult to complete in practice so that purposeful selection of test items is common (6, 7), as in this study design. Because of no standardized psychological tests battery in dementia around the world, it will sometimes lead to a vague outcome when choosing a different test
item, or even with conflicting finding. In fact, we are frequently puzzled by so many kinds of psychological tests with inconsistent results. Therefore, how to select suitable battery to present a unique and constant
endpoint and supporting by other test items will become important on studying the cognitive functioning (8). At present, the cognitive assessments are mostly dependent to the selective tested item. We have met same problems. Recently, we have finished our analysis in polychlorinated
biphenyls (PCBs) exposed elderly of age>=60 years old and matched controls, with selective neuropsychological tests to clarify the cognitive differences after initial toxic outbreak since 1979. In total 328 subjects (exp: control=166:162), mean age 69, to have found an implicated working memory, such as motor and sensory tests (Luria¡¦s criteria) etc, was insignificant between both. Yet, the explicated working memory (i.e., Attention and Digit Span, Verbal Memory Recalls, Visual Memory Span, etc)
by adjusting the confounders, is statistically significant. Our results (un-published) are not quietly alike to the report previously in literature by using the different tests battery (9). Although the toxic exposure and the degenerative process affecting the cognition are
different, it is worthy to learn how to choose a standardized, world-wide base with a good validity, and can be supported by other satellite tests in clinical practice (10).
This study reveals significant differences between PDD and DLB in visual recognition memory using DMS-48. We have some comments on them. Too small sample sizes, as mentioned by the authors, will have a wide variable
effects when adding more cases; the inconsistent result of visual memory test (i.e., BVRT); not exclude the possibility of ¡§by chance¡¨ alone (11); and the bias in this small comparative study. Although the Receive
and Operating Characteristic curve (ROC) demonstrates a significant difference between PDD and DLB with sensitivity 83%, and specificity 87% (an arbitrary cut-off point, the theoretical level of each independent
axis will meet on a parabolic curve at the farthest point from the diagonal indicating of a good sensitivity) (12), it may be better used in differentiating from good or bad outcome in PDD or DLB, and should be warranted with false negative interpretation in this creative and time-
consuming study.
References
1. Harding AJ, Broe GA, Halliday GM. Visual hallucinations in Lewy body disease relate to Lewy bodies in the temporal lobe. Brain. 2002; 125: 391-340.
2. Yamamoto R, Iseki E, Murayama N,et al. Investigation of Lewy pathology in the visual pathway of brains of DLB.J Neurol Sci. 2006; 246: 95-101.
3. Matsui H, Udaka F, Tamura A, et al. Impaired visual acuity as a risk factor for visual hallucinations in Parkinson's disease. J Geriatr Psychiatry Neurol. 2006; 19: 36-40.
4. Mosimann UP, Mather G, Wesnes KA, et al. Visual perception in Parkinson disease dementia and dementia with Lewy bodies. Neurology. 2004; 63: 2091-2096.
5. Mondon K, Gochard A, Marque A, et al. Visual recognition memory differentiates dementia with Lewy bodies and Parkinson's disease dementia. J Neurol Neurosurg Psychiatry. 2007.(Epub ahead of print).
6. Fiedler N, Feldman RG, Jacobson J, et al. The assessment of neurobehavioral toxicity: SGOMSEC joint report. Environ Health Perspect 1996; 104:179-191.
7. Golden CJ. Screening Test for the Luria-Nebraska Neuropsychological Battery: Adult and Children¡¦s Forms. Western Psychological Services, Los Angeles, 1987.
8. Anger WK. Lessons learned-15 years of the WHO-NCTB: A review. Neurotoxicology 2000; 21: 837-846.
9. Schantz SL , Donna MG, Elena P, et al. Impairment of memory and learning in older adults exposed to polychlorinated biphenyls via consumption of Great Lake fish. Environ Health Perspect 2001; 109: 605-611.
10. Zhou W, Liang Y, Christiani C, et al. Utility of the WHO Neurobehavioral Core Test Battery in Chinese workers¡X A meta-analysis. Environ Res 2002; 88: 94-102.
11. Kaufman AS. PCBs-Induced Impairments in Older Adults: Critique of Schantz et al.¡¦s Methodology and Conclusions. Environ Health Perspect 2002; 110: 70-71.
12. Zweig MH, Campbell G. Receiver-operating characteristic (ROC) plots: a fundamental evaluation tool in clinical practice. Clin Chem 1993; 39: 561-7.
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...
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.
We read with interest the recent article by Vulliemoz et al, in which the authors describe a striking improvement of ataxia and epilepsy following treatment with glucocorticoids, azathioprine, levetiracetam and clobazam
in a patient with high titers of antibodies against glutamic acid decarboxylase (GAD) (1).
As reflected in that article, the underlying molecular mechanisms are thought to b...
We read with interest the recent article by Vulliemoz et al, in which the authors describe a striking improvement of ataxia and epilepsy following treatment with glucocorticoids, azathioprine, levetiracetam and clobazam
in a patient with high titers of antibodies against glutamic acid decarboxylase (GAD) (1).
As reflected in that article, the underlying molecular mechanisms are thought to be different in the various medical conditions associated with anti-GAD antibodies. For instance, anti-GAD antibodies related to stiff-
person syndrome (SPS) behave differently from those related to uncomplicated insulin-dependent diabetes mellitus (IDDM) in that SPS-related antibodies reduce GABA synthesis in vitro, while those in IDDM do not (1).
Accordingly, the cause of the elevated anti-GAD antibody titres found in two recently described siblings with the unusual association of familiar autoimmune polyglandular syndrome type 1 (APS1) with trabecular fibre myopathy, was considered to be an immunological epiphenomenon
because no ataxia, epilepsy, nystagmus or SPS were present. Another sibling had vitamin B12 deficiency, atrophic gastritis and anti-intrinsic factor antibodies in addition to a highly complex form of APS1, although
anti-GAD antibodies could not be determined (2).
Vulliemoz el al affirm that the treatment of anti-GAD antibodies related neurological conditions relies on immunosuppression or enhancement of GABA activity (1). These authors fully agree with that statement, even
more so considering that GABA enhancement with gabapentin has proved useful to ameliorate epilepsy (1), SPS (3) and cerebellar ataxia (4).
The only weakness of an otherwise accurate and informative article is the improper use of the acronym “GABA”. GABA should stand for g-aminobutyric acid, the most important inhibitory neurotransmitter in the nervous system. On the contrary, GABA is referred to as g-hydroxybutiric acid (GHB) by Vulliemoz et al (1). Likewise, GAD does not catalyse the transformation of glutamate into GHB; it may be formed from its precursors g-butyrolactone and 1,4-butanediol, or from succinic semialdehyde by the enzyme succinic semialdehyde reductase (5).
It may be interesting to point out that GHB is a closely related molecule to GABA, and it is present in the brain, where it may interact with metabotropic GABA-B receptors, exercising an inhibitory action on neuronal function, and with specific GHB receptors. It also affects the
neuromodulatory dopaminergic, serotoninergic, cholinergic and opioid systems. GBH causes sedation, drowsiness and coma, even death due to respiratory depression, and it is consumed as a drug of abuse due to the feeling of placidity and well being it may generate. In combination with ethanol or other drugs, agitation and aggressiveness are possible. No specific antidotes are available. GBH was formerly used as an anaesthetic agent in clinical practice, and it has shown efficacy in the treatment of
cataplexy associated with narcolepsy (5). As the medical use and abuse of GHB is increasing in Europe, it may be helpful for physicians to be familiar with the potentially dangerous effects of this drug.
José Gazulla, Isabel Benavente
References
1. Vulliemoz S, Vanini G, Truffert A, Chizzolini C, Seeck M. Epilepsy and cerebellar ataxia associated with anti-glutamic acid decarboxylase antibodies. J Neurol Neurosurg Psychiatry 2007; 78: 187-189.
2. Gazulla Abío J, Benavente Aguilar I, Ricoy Campo JR, Madero Barrajón P. Miopatía con fibras trabeculares asociada a síndrome poliglandular autoinmune tipo 1 familiar. Neurología 2005; 20: 702-708.
3. Rakocevic G, Raju R, Semino-Mora C, Dalakas MC. Stiff person syndrome with cerebellar disease and high-titer anti-GAD antibodies. Neurology 2006; 67:1068-1070.
4. Gazulla J, Errea JM, Benavente I, Tordesillas C. Treatment of ataxia in cortical cerebellar atrophy with the GABAergic drug gabapentin. A preliminary study. Eur Neurol 2004; 52: 7-11.
5. Drasbek KR, Christensen J, Jensen K. Gamma hydroxybutirate- a drug of abuse. Acta Neurol Scand 2006; 114: 145-156.
Dear Editor,
To determine the effects of drugs on the progression of disease in Alzheimer’s is a major target. We read with great expectation the paper by Ellul et cols. dealing with this issue (1). In this study, the drugs prescribed to a cohort of 224 patients with Alzheimer’s were recorded at initial assessment and then correlated with progression of the disease over the next 12-month period defined as an inc...
Dear Editor,
I read with interest the editorial commentary on the possible causal link between cannabis consumption and stroke as reported by Mateo et al based on their short case report (Journal of Neurology Neurosurgery and Psychiatry 2005;76:435-437).
I wish to make few comments on the purported causal relationship. Hashish is made from trichomes which are present with varying amount of surplus pla...
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 M...
Dear Editor,
Neurology is not immune to fashion. Neuroscientists follow dictates of research fashion quite precisely like their fellow humans follow fashion in food, dress, literature, music or other trivial pursuits. Transcranial magnetic stimulation (TMS) has gripped the imagination and the intellect of neurologists in the last few years. That TMS could possibly be effective for disorders as varied as chronic ne...
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 ov...
Dear Editor,
I have read the proceedings of the Association of British Neurologists and in particular the report of Murphy et al on Intracranial haemorrhage in the Hypereosinophilic syndrome. They claim that this has not been previously reported. This is incorrect. I had a short report published on this topic in the JNNP in 1990, the reference is 1990; 53:440-441. I will be interested in your comments.
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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...
Dear Editor,
This is an interesting research about the recognition of visual memory between Parkinson¡¦s Disease Dementia (PDD) and Dementia of Lewy Body (DLB). We know much about the formed visual hallucination and visual dysfunction in shape and color in both disease entities (1-4), but not easily elucidated the visual storage or retrieving disorder partly because of the aging and systemic factors affecting the...
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...
Dear Editor,
We read with interest the recent article by Vulliemoz et al, in which the authors describe a striking improvement of ataxia and epilepsy following treatment with glucocorticoids, azathioprine, levetiracetam and clobazam in a patient with high titers of antibodies against glutamic acid decarboxylase (GAD) (1).
As reflected in that article, the underlying molecular mechanisms are thought to b...
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