The authors present an interesting study using EEG as a tool for the diagnosis of Lewy Body Dementia. They however did not comment on a number of major confounders.
In their methodology the authors state that the patients were kept "awake as much as possible", but do not comment if they were successful. How many patients with Lewy body dementia attained deeper stages of sleep as compared to...
The authors present an interesting study using EEG as a tool for the diagnosis of Lewy Body Dementia. They however did not comment on a number of major confounders.
In their methodology the authors state that the patients were kept "awake as much as possible", but do not comment if they were successful. How many patients with Lewy body dementia attained deeper stages of sleep as compared to those with Alzheimers disease? Were all the studies done at
the same time of the day? Did some some patients (such as those with Alzheimer's disease) have a cup of coffee before the study? Did all these patients have a good nights sleep the night before or some patients were
sleep deprived? Did all or some of these patients had a good meal before the study? Did the authors check or inquire about their blood sugars? Were there any concurrent and coexisting medical conditions? The authors
mention that all these patients had an MRI of the brain but do not mention the results. Were there significant differences on MRI between the different groups?
I realize that it would be very tedious and at times impossible to control for all these confounders. But without considering all the above issues it would be naive to suggest a high sensitivity and specificity of
EEG in the diagnosis of Lewy Body or other dementias.
In the light of the recent review, which highlighted the inability of most tests of cognitive function to specify what "proportion of people who are classified by the screen as impaired who really are impaired"(ie the
positive predictive value of the test)(1) it will be difficult, if not impossible, to apply the golden rule from the case of Kenward v Adams(2) to patients who are being evaluated for...
In the light of the recent review, which highlighted the inability of most tests of cognitive function to specify what "proportion of people who are classified by the screen as impaired who really are impaired"(ie the
positive predictive value of the test)(1) it will be difficult, if not impossible, to apply the golden rule from the case of Kenward v Adams(2) to patients who are being evaluated for their capacity to make a will(3),
using the tests listed in Table 2, except for the one test which specified a positive predictive value of 91% and a negative predictive value of 96% for Alzheimer's disease. Even that test failed specify positive predictive
values for the other subtypes of dementia, namely, vascular dementia, frontotemporal dementia, and Lewy body dementia, respectively.
Accordingly, the specification in the golden rule, that the making of a will by an aged testator or a testator who has suffered a serious illness "ought to be witnessed or approved by a medical practitioner who satisfies himself of the capacity and understanding of the testator"(2) is one whose fulfilment will have to await more rigourous studies evaluating the positive predictive value in each of the subtypes of dementia
Oscar M Jolobe
References
(1) Cullen B., O'Neill B., Evans JJ., Coen RF., Lawlor BA
A review of screening tests for cognitive impairment
Journal of Neurology, Neurosurgery, and Psychiatry 2007:78:790-99
(2) Kenward v Adams(1975) Times 29 November
(3)Jacoby R., Steer P
How to assess capacity to make a will
British Medical Journal 2007:335:155-7
I read with great interest the letter entitled “Resolution of transverse sinus stenoses immediately after CSF withdrawal in idiopathic intracranial hypertension” recently published in JNNP by Scoffings et al(1). This letter presents the case history of a 35 yrs old patient with idiopathic intracranial hypertension (IIH) who had bilateral venous outflow stenosis of the transverse sinuses, which resolved im...
I read with great interest the letter entitled “Resolution of transverse sinus stenoses immediately after CSF withdrawal in idiopathic intracranial hypertension” recently published in JNNP by Scoffings et al(1). This letter presents the case history of a 35 yrs old patient with idiopathic intracranial hypertension (IIH) who had bilateral venous outflow stenosis of the transverse sinuses, which resolved immediately following the removal of CSF. The authors suggest, that the elevated venous pressures noted in this patient were caused by the collapse of the transverse sinuses (1) and go on to assert that stent insertion should not be used as it would not be curative in patients with similar dynamic stenoses. This suggestion is proposed because logically, if the raised CSF
pressure has caused the venous sinus collapse, then the elevated venous pressure cannot also be the cause of the raised CSF pressure. I wish to discuss whether the cause and effect relationship as outlined, is the only one possible, given the data as presented.
The majority of patients with IIH have morphologic stenoses in their venous outflow(2). Many of these stenoses reduce the outflow by greater than 70% in area (as in the current patient) and would be deemed to be
significant if found on the arterial side of the vascular tree. Direct manometry has shown the pressure gradients across these stenoses to average 24 mmHg(3)(19 mmHg in this case) which would also suggest that these stenoses were significant by the usual criteria. Finally, I have
measured the arterial inflow and venous outflow in 21 patients with IIH and stenoses and found on average that there is a 13% reduction in the sagittal sinus outflow as a percentage of the inflow in IIH (4). This suggests 140 ml/min bypasses the dominant out flow stenosis via collateral vessels(4), again suggesting significance.
Can we reconcile the apparent significant nature of the stenoses, with the fact that they occur secondary to the CSF pressure? Intracranial pressure (ICP) is dependant on a balance between CSF production and reabsorption. Davson et al modeled the relationship between ICP and the formation and reabsorption of CSF showing that, ICP= Rout x FRCSF + PSS where Rout is the resistance of CSF outflow, FRCSF is the formation rate of CSF and PSS is the sagittal sinus pressure(5). In Scoffings et als patient, the opening pressure at the time of venous pressure measurement was 26 cm H2O (or 19 mmHg) and the sagittal sinus pressure was 30 mmHg. Indicating that the gradient from CSF to sagittal sinus was –11 mmHg. This
is difficult to reconcile given the need for a pressure gradient of +2-6 mmHg, for CSF to be reabsorbed, suggesting either an error in CSF pressure measurement was made or that the CSF pressure was not at steady state when
the measurement occurred. Irrespective, it appears safe to assume that the gradient was not above the normal range. Similarly, in the 21 IIH patients studied by King et al, a mean CSF pressure of 27 mmHg and sagittal sinus pressure of 22 mmHg, gave a CSF-SSS gradient of 5 mmHg(3), which is in the normal range (2-6 mmHg). Rearranging Davson’s equation we find that the CSF-SSS pressure gradient is equal to the product of the CSF production rate and the resistance to flow across the arachnoid granulations i.e.
ICP- PSS = Rout x FRCSF. Malm et al used a constant flow technique(6) to measure FRcsf and showed it be normal in this condition. If the gradient is normal and the
formation rate is normal, then the Rout must also be normal in IIH. Therefore, the elevated venous pressure is the sole variable bringing about the elevation in CSF pressure despite itself being secondary to the elevated CSF pressure. This indicates that a feed back loop must exist where both the CSF pressure and venous pressure are cause and effect, i.e. both being a mixture of the chicken and the egg, hence an omelette. It follows that this condition could be cured by attacking either side of the
feed back loop i.e. reducing the CSF pressure by shunt or lumbar puncture (secondarily opening the stenosis) or stenting open an overly compliant transverse sinus will break the loop. Thus, I believe that the assertion by Scoffings et al that stenting should not be offered to those with IIH and collapsible stenoses is not necessarily correct. Ultimately, whether the front line treatment of IIH associated with collapsible venous outflow is stenting or shunt insertion will depend on the relative morbidity of these procedures and their long-term success rates.
Yours sincerely
Grant A Bateman, MBBS FRANZCR
Department of Medical Imaging
John Hunter Hospital
References
1. Scoffings DJ, Pickard JD, Higgins JN. Resolution of transverse sinus stenoses immediately after CSF withdrawal in idiopathic intracranial hypertension. J Neurol Neurosurg Psychiatry 2007; 78:911-912.
I greatly enjoyed reading the paper ePublished on June 19th. The finding that plaque inflammation, detected by USPIO MR imaging, is present even within contralateral asymptomatic plaques is similar to that noted in
recent FDG PET studies of atherosclerosis. Using plaque FDG uptake as a marker of inflammation, we (Rudd et al Circulation 2002) found that symptomatic lesions had about 30% more inflammat...
I greatly enjoyed reading the paper ePublished on June 19th. The finding that plaque inflammation, detected by USPIO MR imaging, is present even within contralateral asymptomatic plaques is similar to that noted in
recent FDG PET studies of atherosclerosis. Using plaque FDG uptake as a marker of inflammation, we (Rudd et al Circulation 2002) found that symptomatic lesions had about 30% more inflammation within them than contralateral asymptomatic lesions, a finding since replicated by other
groups (Davies et al Stroke 2005, Tawakol et al JACC 2006).
I agree with the authors' conclusions that arterial inflammation is likely to be a pan-vascular phenomenon, and hence the urgent need for systemic rather than local therapies aimed at plaque stabilisation.
The next generation of studies aimed at functional imaging of plaque over time, and correlation with subsequent clinical events will be crucial, however, to validate this important area of research.
I am pleased to respond to Dr Sandip Kumar Dash’s letter dated 3rd July 2007. I wish to reassure Dr Kumar Dash that the home based exercise programme used in the trial was built on the published evidence and the consensus of physiotherapists at the time. It included six levels of
exercise progression and strategies for movement initiation and compensation as well as fall prevention.
I am pleased to respond to Dr Sandip Kumar Dash’s letter dated 3rd July 2007. I wish to reassure Dr Kumar Dash that the home based exercise programme used in the trial was built on the published evidence and the consensus of physiotherapists at the time. It included six levels of
exercise progression and strategies for movement initiation and compensation as well as fall prevention.
I must draw to Dr Kumar Dash’s attention the limitations of the two papers to which he makes reference. Sidaway’s paper (2006) was an account of a single subject and therefore, although interesting, was not generalisable. Morris’ paper (2000) was a theoretical paper on modelling
therapy. In her concluding paragraph she states ‘Randomised clinical trials are now needed to evaluate the specific effects of physiotherapy and to validate this model of care for people with PD’.
Our RCT was testing therapy and did where appropriate include techniques for initiating movement (cues)as part of the management. The results of our study and those of Nieuwboer et al JNNP 2007; (78) 2: 134-140 (specific focus on cueing techniques), which were published within months of each other, will make major contributions to what was previously a spartan evidence base for physiotherapy for people with PD.
I have read the article by Ann Ashburn et al (1), with interest and found it to be very useful for improving the quality of life of patients of Parkinson’s disease by giving them home exercise. This study is having a large number of patients and showed a reduction of fall and near fall in patients of Parkinson’s disease. How- ever I would like to have a few comments.
I have read the article by Ann Ashburn et al (1), with interest and found it to be very useful for improving the quality of life of patients of Parkinson’s disease by giving them home exercise. This study is having a large number of patients and showed a reduction of fall and near fall in patients of Parkinson’s disease. How- ever I would like to have a few comments.
This study (1), showed a significant improvement in functional reach test at 6 months in patients of exercise group. Though the fall rates in exercise group did not reach statically significant, there was a trend towards lower fall rates in exercise group at 8 weeks and at 6 months, the near fall rates were significant.Sidaway Ben et al (2) in their study found that 1 month training with visual cues was successful in establishing a lasting improvement in gait speed and stride length, while increasing the stability of underlying motor control system. Meg E Morris (3) also suggested that physical therapy offers symptomatic relief by teaching people strategies for bypassing defective basal ganglion in order
to move free easily. He has suggested physical therapy using cues and attentional strategies in different stages of the disease, according to Hoehn and Yahr scale. Over the years various tricks like visual tricks, movement tricks, mental tricks, auditory and tactile tricks have been devised to decrease the duration of freezing .These tricks help one to take the next step more quickly.
So in the present study (1), if in the home based exercise progamme cues would have been done as a part of protocol in the study, then reduction in fall and injurious fall among participants in the exercise group could have reached a significant value and might have caused a
difference in Berge balance test, timed up go test, and this would have thrown a light for future home based exercise studies in Parkinson’s disease.
References
1 Ann Ashburn, Louise Fazakarley, Claire Ballinger, Ruth Pickering, Lindsay D McLellan, and Carolyn Fitton--A randomised controlled trial of a home based exercise programme to reduce the risk of falling among people
with Parkinson’s disease. J Neurol Neurosurg Psychiatry 2007; 78: 678-684
2.Ben Sidway,Jenifer Anderson,Garth Davidson,Lucas Martin,Garth Smith,-Effects Of longterm gait training using visual cues in an individual with Parkinsons disease. Physical Therapy, 2006, vol86, no2, 186-194.
3.Meg morris—Movement disorders in people with Parkinsons disease: A model fort physical therapy—Physical Therapy,2000,vol 80,no 6,578-597.
Ringleb and co-authors concluded that the use of magnetic resonance imaging to select octogenarian patients with acute ischaemic stroke for thrombolytic therapy increases safety(1). They dismiss the possibility that this apparent benefit of MR selection may have been due to selection bias since the NIHSS scores were similar in those in whom MRI was applied versus those not(1). However, we have shown...
Ringleb and co-authors concluded that the use of magnetic resonance imaging to select octogenarian patients with acute ischaemic stroke for thrombolytic therapy increases safety(1). They dismiss the possibility that this apparent benefit of MR selection may have been due to selection bias since the NIHSS scores were similar in those in whom MRI was applied versus those not(1). However, we have shown that a significant proportion of older patients have relative or absolute contraindications
to MR scanning unrelated to the severity of their stroke (2). Hence, in our view, the apparent reduction in intracerebral haemorrhage by the use of MR selection could well be mainly accounted for by the MR patients having less non-stroke co-morbidity and frailty (eg the need for a pacemaker); these non-stroke co-morbidities were not assessed in the paper. Furthermore, overall outcome, in terms of survival or survival free of disability was not significantly better in those selected by MR compared with those selected by CT.
We would also take issue with their description of their own study and the observational studies included in their systematic review as trials. This is misleading, since, in common usage, ‘trial’ is usually restricted to study designs in which a treatment allocation is determined
strictly randomly and the next allocation is concealed from the clinician.
We therefore conclude that this paper does not support the argument that patients (of any age) presenting more than 3 hours after stroke onset should be selected by the use of MR DWI/PWI imaging. Furthermore, the DIAS-2 trial, among patients with an acute ischaemic stroke 3-9 hours after stroke onset, selected for the presence of mismatch on MR DWI-PWI, did not provide evidence that thrombolysis (with i.v. desmoteplase) was of net benefit.(3) This result does throw the 'mismatch' concept into some doubt.
Furthermore, immediate access to MR scanning for acute stroke patients is problematic in many non-specialist hospitals admitting patients with stroke, so any requirement for MR pre-selection might exclude many patients from thrombolytic therapy. We should therefore await further randomised evidence (e.g. from the ongoing EPITHET study) on the utility of ‘mismatch’ on MR as a selection criteria for thrombolysis before making recommendations.
In the meantime, we do, however, agree with the concluding sentence of Ringleb’s article which states the only way to obtain reliable evidence on the effects of thrombolytic therapy beyond 3 hours, especially in octogenarians, is to include such patients in IST-3,(4) the only ongoing randomised trial which permits recruitment of patients over 80.
Peter Sandercock, DM
Joanna Wardlaw, MD
Richard Lindley, MD
Stefano Ricci, MD
On behalf of the IST-3 collaborative group
References
(1) Ringleb PA, Schwark C, Kohrmann M, Kulkens S, Juttler E, Hacke W, et al. Thrombolytic therapy for acute ischaemic stroke in octogenarians: selection by magnetic resonance imaging improves safety but does not improve outcome. J Neurol Neurosurg Psychiatry 2007 Jul 1; 78(7):690-3.
(2) Hand PJ, Wardlaw JM, Rowat AM, Haisma JA, Lindley RI, Dennis MS. Magnetic resonance brain imaging in patients with acute stroke: feasibility and patient related difficulties. J Neurol Neurosurg Psychiatry 2005 Nov; 76(11):1525-7.
(3) Hacke W, Furlan A. Results From The Phase III Study Of Desmoteplase In Acute Ischemic Stroke Trial 2 (Dias 2). Cerebrovasc Dis 23 (suppl 2), 54. 2007.
(4) Whiteley W, Lindley R, Wardlaw J, Sandercock P, International Stroke Trial Collaborative Group. Third International Stroke Trial. International Journal of Stroke 1, 172-176. 2006.
This is a very interesting article. Dr. Young, et.al. report a rare sub-group of headache patients. Patients with unilateral motor symptom is commonly only seen in tertiary health center. The motor symptom will drive
the patients for visiting the health centers with full facilities. It is consistent with the facts that most headache patients want to know the origin of the headache. This article showe...
This is a very interesting article. Dr. Young, et.al. report a rare sub-group of headache patients. Patients with unilateral motor symptom is commonly only seen in tertiary health center. The motor symptom will drive
the patients for visiting the health centers with full facilities. It is consistent with the facts that most headache patients want to know the origin of the headache. This article showed that most patients experiences
significant impact of their headache. Allodynia can be very disturbing.
About 33% patients with MUMS lost their jobs because of the headache. The number is very significant. The patients with MUMS will also receive more procedure either diagnostic procedure and therapeutic procedure. In our
neurological daily practice, most patients ask "where does this headache come from?", "Is it any serious problems in my head?", or "is there any brain tumor?". Patients with motor symptoms surely have more anxiety and concern about their disease. This is possible, because about 40% patients has been told by the doctor that they have stroke. When the imaging is normal, almost 50% patients believed that their symptoms is migraine related. The MUMS must be recognized correctly, and treated well to minimize the disability. The good information for the patients will be also necessary to improve the compliance.
The role of inflammation in the etiopathogenesis of Alzheimer’s disease (AD) has been exhaustively analyzed by several authors, with a special focus on cytokines such as Tumor Necrosis Factor alpha (TNF-alpha), Interleukin-1 and Interleukink-6, demonstrated to be evidently connected with the neuroinflammatory processes; an augmented production of these cytokines have been revealed in AD subjects while a def...
The role of inflammation in the etiopathogenesis of Alzheimer’s disease (AD) has been exhaustively analyzed by several authors, with a special focus on cytokines such as Tumor Necrosis Factor alpha (TNF-alpha), Interleukin-1 and Interleukink-6, demonstrated to be evidently connected with the neuroinflammatory processes; an augmented production of these cytokines have been revealed in AD subjects while a deficiency have been shown in the late phase of the disorder (1).
Polymorphisms of genes encoding for cytokines have also been associated to AD (2). Recently Bossù et al. (3) demonstrated that Interleukin 18 promoter polymorphisms are involved in the prediction of the risk and outcome of AD.
In our case-control study we analyzed IL-18 gene promoter polymorphisms in AD patients and healthy controls in order to verify the involvement of these genetic variations in the onset of AD.
A hundred and eleven AD patients ( 79 F/ 32 M, mean age 79.47± SD 6.30) and 111 non-demented sex- and age- matched healthy controls (HC, 76 F/35 M, mean age 79.98± SD 6.36) were enrolled for this study.
All patients were Caucasian, living in Northern Italy and selected from a larger ambulatory population attended to at the Geriatric Department of the Ospedale Maggiore IRCCS, University of Milan, Italy. There were no significant differences between the groups in age or education level. Diagnosis of probable AD was performed according to standard clinical procedures and following the DMS IV and NINCDS-ADRDA criteria. The cognitive and functional performances were assessed using mini-mental state evaluation (MMSE), activities of daily living (ADL), instrumental activities of daily living (IADL) as well as an extensive neuropshycological evaluation. Every subject had undergone a recent brain magnetic resonance imaging (MRI)/computed tomography (CT) scan. Criteria for the diagnosis of normal cognition were as follows: (a) no active neurological or psychiatric disorders; (b) any ongoing medical problems or related treatments not interfering with cognitive function; (c) a normal neurological exam; (d) no psychoactive medications; (e) independently functioning community dwellers. In order to minimize the risk of possible inflammatory processes, all subjects selected showed no clinical signs of inflammation (e.g. normal body temperature, no concomitant inflammatory condition) and normal blood chemistry levels (red blood cell sedimentation rate, albumin, transferrin and C reactive protein plasma levels).
Genomic DNA was extracted by using the GenomePrep kit (GE Healthcare). Amplification of IL-18 promoter region was performed by using primers (Primer Reverse 5’- GGGCAATGGAAGTCGAAATAAAGT -3’ Primer Forward 5’- GAAAGTTTTAACACTGGAAACTGCAA -3’ ) designed using the software Primer Express 2.0 (Applied Biosystems, Foster City, CA) according to the human sequences available in GenBank.
PCR reactions were carried out in a GeneAmp 9700 Thermal cycler (Applied Biosystems, Foster City, CA) using PCR buffer 1X, 1 unit of Taq Gold, 0.2mM dNTPs and MgCl2 2 mM). The cycling was performed with an initial denaturation for 10 min at 95°C, followed by 40 cycles at 95°C for 20 s, at the annealing temperature of 60°C for 30 s and 72°C for 30 s with a final extension to 72°C for 7 min. DNA sequencing of PCR products was performed using the BigDye Terminator Cycle Sequencing Ready Reaction Kit 2.0 (Applied Biosystems, Foster City, CA). DNA sequences were run on an automated ABI Prism 3100 Genetic Analyser (Applied Biosystems, Foster City, CA). Sequences were handled using SeqScape 1.0 Software.
ApoE genotypes were determined by PCR amplification of a 234 base-pair fragment of exon 4 of the ApoE gene followed by digestion using Cfo1, according to standard protocols. Restriction patterns were revealed by 2% agarose gel electrophoresis.
Allele and genotype frequencies were calculated by direct gene counting and the differences were analyzed using the exact Fisher test; a p value less than 0.05 was considered statistically significant. Haplotype frequencies were calculated using the software Arlequin 3.01 (http://cmpg.unibe.ch/software/arlequin3/).
Three polymorphisms have been studied in the promoter region of the IL-18 gene at position -137 (G/C), - 607 (C/A) and -656 (G/T). Allelic and genotype frequencies of IL-18 promoter polymorphisms as well as haplotypes distribution in AD patients and controls are reported in Table 1. The distribution of the allelic and genotype frequencies of -137 (G/C), - 607 (C/A) and -656 (G/T) IL-18 promoter polymorphisms was in Hardy-Weimberg equilibrium in AD patients and controls.
No significant difference was detected for the three IL-18 SNPs between AD patients and controls. The haplotypes distribution also did not show any difference within AD subjects and controls.
We also performed ApoE genotyping and we evidenced, as expected, that the presence of the ApoE4 in the total AD patient population was significantly higher than in the control population (27% vs. 14% chi-sq=5.53 p=0.0188). However no significant association among ApoE variant alleles and the three studied polymorphisms was found in healthy controls as well as in AD patients (p=n.s. for all comparison).
Our results are not in agreement with those obtained by Bossù et al. (3), who demonstrated an association between two IL-18 polymorphisms (-137 G/C and -607 C/A) and the suceptibility and clinical outcome of AD.
In our study we analyzed the two functional IL-18 polymorphisms (-137 G/C and -607 C/A) and an additional polymorphisms at position -656: no association with AD was found.
Even if we do believe that the innate immune system - and more specifically cytokines - can play a role in the etiopathogenesis of AD having been widely demonstrated a chronic inflammatory response in AD brains, our negative results simply indicate that the association of IL-18 promoter polymorphisms with AD is not so strong, being AD a multifactorial disease.
Finally, as disaccording findings concerning the IL-18 production have been obtained by different authors in AD patients (4,5) it is not surprising that also the distribution of IL-18 functional polymorphisms could vary in different populations.
We do think, as also stated by Bossù et al. that further studies performed on larger Italian AD patients cohorts could contribute to clarify the role of IL-18 in AD.
Ludovica Segat
Michele Milanese
Beatrice Arosio
Sergio Crovella
References
1) Sala G, Galimberti G, Canevari C, Raggi ME, Isella V, Facheris M, Appollonio I, Ferrarese C. Peripheral cytokine release in Alzheimer patients: correlation with disease severity. Neurobiol Aging. 2003 Nov;24(7):909-14.
2) Yucesoy B, Peila R, White LR, Wu KM, Johnson VJ, Kashon ML, Luster MI, Launer LJ. Association of interleukin-1 gene polymorphisms with dementia in a community-based sample: the Honolulu-Asia Aging Study. Neurobiol Aging. 2006 Feb;27(2):211-7.
3) Bossu P, Ciaramella A, Moro ML, Bellincampi L, Bernardini S, Federici G, Trequattrini A, Macciardi F, Spoletini I, Di Iulio F, Caltagirone C, Spalletta G. Interleukin-18 gene polymorphisms predict risk and outcome of Alzheimer's disease. J Neurol Neurosurg Psychiatry. 2007 Feb 13; [Epub ahead of print].
4) Lindberg C, Chromek M, Ahrengart L, Brauner A, Schultzberg M, Garlind A. Soluble interleukin-1 receptor type II, IL-18 and caspase-1 in mild cognitive impairment and severe Alzheimer's disease. Neurochem Int. 2005 Jun;46(7):551-7.
5) Malaguarnera L, Motta M, Di Rosa M, Anzaldi M, Malaguarnera M. Interleukin-18 and transforming growth factor-beta 1 plasma levels in Alzheimer's disease and vascular dementia. Neuropathology. 2006 Aug;26(4):307-1
Table 1: Allele, genotype and haplotype frequencies of IL-18 polymorphisms in Alzheimer’s disease subjects (AD) an healthy controls (HC).
We would like to contribute on the article entitled “Radiological findings in individuals at high risk of schizophrenia and patients with first episode psychosis” by Borgwardt et al. [1] and on a letter by the
same group [2], in which they comment on our own paper investigating this issue [3]. The authors highlight that they have found [1] a lower prevalence of cavum septum pellucidum (CSP) both in su...
We would like to contribute on the article entitled “Radiological findings in individuals at high risk of schizophrenia and patients with first episode psychosis” by Borgwardt et al. [1] and on a letter by the
same group [2], in which they comment on our own paper investigating this issue [3]. The authors highlight that they have found [1] a lower prevalence of cavum septum pellucidum (CSP) both in subjects with first-episode schizophrenia (3.3%) and individuals at high risk for psychosis (5.7%), when compared to our findings in schizophrenic patients (21.1%).
We agree with Borgwardt et al. [2] that their use of a qualitative rather than a quantitative method may explain their finding of a lower estimated frequency of CSP. We would also argue that the acquisition of high-resolution, 1-mm contiguous MRI brain slices in our study may have led to a more accurate estimation of the prevalence of CSP, as well as allowing the quantitative assessment of their size. Borgwardt et al. [2] also stressed the value of searching for a wider range of structural brain anomalies in psychosis, instead of focusing on a single abnormality, such as the CSP. In regard to that, MRI images in our study [3] were also inspected visually for the presence of other gross anomalies in midline brain structures, by a consensus between two neuroradiologists blind to sex, diagnosis and clinical status of subjects. At this assessment, one of the patients with schizophrenia was found to have a lipoma adherent to the anterior face of the splenium of the corpus callosum; one other case
presented a parietal hemangioma, another patient presented total agenesis of the corpus callosum, while a fourth patient had a complete non-fusion of the entire length of the septum pellucidum – an anomaly termed ‘combined CSP and cavum vergae’. None of the observed abnormalities
implicated in a change in the diagnosis from DSM-IV schizophrenia to psychotic disorder due to an ‘organic’ medical condition. We did not find any other gross or pathological midline abnormalities in any of the
subjects studied. However, the following normal or minor brain variations were additionally found (data not presented before), only in the schizophrenia group: asymetrical ventricular system (n=4) and presence of
arachnoid cyst (n=1). Thus, taking all those findings together, it is possible to conclude that in our sample, there is also a significantly (p = 0.001) higher proportion of radiological findings in patients with
schizophrenia (9 of 38 or 23.7%) compared to healthy controls (none of 38). Although this was not the main objective of our study and the qualitative MRI assessment we have used was not standardized, our results are supportive of the findings reported by Borgwardt et al. [1] We suggest that future MRI studies, instead of focusing on either qualitative or quantitative assessments only, should systematically employ both approaches to evaluate the same sample. This may be of greater help for
our understanding of the role of developmental anomalies in the neuropathology of schizophrenia.
References
[1] S.J. Borgwardt, E.W. Radue, K. Götz, et al., Radiological findings in individuals at high risk of schizophrenia and patients with first episode psychosis. J Neurol Neurosurg Psychiatry 2006;77:229–33.
[2] Borgwardt SJ, Radue EW, Riecher-Rossler A. Cavum septum pellucidum in patients with first episode psychosis and individuals at high risk of psychosis. Eur Psychiatry 2006; 22:264.
[3] J.A. De Souza Crippa, A.W. Zuardi, G.F. Busatto, et al., Cavum septum pellucidum and adhesio interthalamica in schizophrenia: an MRI study. Eur Psychiatry 2006; 21: 291–9.
Dear Editor,
The authors present an interesting study using EEG as a tool for the diagnosis of Lewy Body Dementia. They however did not comment on a number of major confounders.
In their methodology the authors state that the patients were kept "awake as much as possible", but do not comment if they were successful. How many patients with Lewy body dementia attained deeper stages of sleep as compared to...
Dear Editor,
In the light of the recent review, which highlighted the inability of most tests of cognitive function to specify what "proportion of people who are classified by the screen as impaired who really are impaired"(ie the positive predictive value of the test)(1) it will be difficult, if not impossible, to apply the golden rule from the case of Kenward v Adams(2) to patients who are being evaluated for...
Dear Sir,
I read with great interest the letter entitled “Resolution of transverse sinus stenoses immediately after CSF withdrawal in idiopathic intracranial hypertension” recently published in JNNP by Scoffings et al(1). This letter presents the case history of a 35 yrs old patient with idiopathic intracranial hypertension (IIH) who had bilateral venous outflow stenosis of the transverse sinuses, which resolved im...
Dear Editor,
I greatly enjoyed reading the paper ePublished on June 19th. The finding that plaque inflammation, detected by USPIO MR imaging, is present even within contralateral asymptomatic plaques is similar to that noted in recent FDG PET studies of atherosclerosis. Using plaque FDG uptake as a marker of inflammation, we (Rudd et al Circulation 2002) found that symptomatic lesions had about 30% more inflammat...
Dear Editor
I am pleased to respond to Dr Sandip Kumar Dash’s letter dated 3rd July 2007. I wish to reassure Dr Kumar Dash that the home based exercise programme used in the trial was built on the published evidence and the consensus of physiotherapists at the time. It included six levels of exercise progression and strategies for movement initiation and compensation as well as fall prevention.
I mu...
Dear Editor
I have read the article by Ann Ashburn et al (1), with interest and found it to be very useful for improving the quality of life of patients of Parkinson’s disease by giving them home exercise. This study is having a large number of patients and showed a reduction of fall and near fall in patients of Parkinson’s disease. How- ever I would like to have a few comments.
This study (1), showed...
Dear Editor
Ringleb and co-authors concluded that the use of magnetic resonance imaging to select octogenarian patients with acute ischaemic stroke for thrombolytic therapy increases safety(1). They dismiss the possibility that this apparent benefit of MR selection may have been due to selection bias since the NIHSS scores were similar in those in whom MRI was applied versus those not(1). However, we have shown...
Dear Editor,
This is a very interesting article. Dr. Young, et.al. report a rare sub-group of headache patients. Patients with unilateral motor symptom is commonly only seen in tertiary health center. The motor symptom will drive the patients for visiting the health centers with full facilities. It is consistent with the facts that most headache patients want to know the origin of the headache. This article showe...
Dear Editor,
The role of inflammation in the etiopathogenesis of Alzheimer’s disease (AD) has been exhaustively analyzed by several authors, with a special focus on cytokines such as Tumor Necrosis Factor alpha (TNF-alpha), Interleukin-1 and Interleukink-6, demonstrated to be evidently connected with the neuroinflammatory processes; an augmented production of these cytokines have been revealed in AD subjects while a def...
Dear Editor,
We would like to contribute on the article entitled “Radiological findings in individuals at high risk of schizophrenia and patients with first episode psychosis” by Borgwardt et al. [1] and on a letter by the same group [2], in which they comment on our own paper investigating this issue [3]. The authors highlight that they have found [1] a lower prevalence of cavum septum pellucidum (CSP) both in su...
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