Displaying 1-10 letters out of 496 published
Reply to Letter: Which target is best for patients with Parkinson's disease? A meta-analysis of pallidal and subthalamic stimulation
We are pleased that Dr. Cyron agrees with our statement. Although our meta-analysis revealed that depression was more frequent in STN DBS relative to GPi DBS, additional randomized trials which investigate long- term outcome including UPDRS, quality of life and adverse events are required to determine which target is more appropriate for patients with PD. We hope our findings and suggestions would be useful for future studies which provide valuable evidence as meta-analyses helped to establish various treatment options historically.
Conflict of Interest:
This is a timely contribution to an issue overdue. STN-stimulation has been the undisputed mainstay of DBS for Pakinson's disease more than a decade. Reports on deleterious side effects mainly in the field of cognition and emotion however accumulate. While the rather subtle effects on cognitive abilities have been the subject of a plethora of publications, changes in personality and behavior remain underreported. Yet it is these changes that can have catastrophic impacts on the wellbeing of patients and their relatives. In my experience with GPI stimulation behavior and mood are by far less affected or even improved. In the light of these complications the advantage of greater reductions in medication with STN stimulation appears less relevant. Depleting patients of badly needed dopamin may even worsen axial symptoms, emotional state and incentive. I therefore strongly agree with the author's statement, that it is now time to clarify this issue involving an appropriate number of patients.
Conflict of Interest:
Temozolomide for seizure control in low-grade gliomas: role of malignant degeneration
We were particularly appreciated the paper by Koekkoek and colleagues1 on temozolomide (TMZ) and seizure frequency after low-grade gliomas (LGG) in a retrospective study. Interestingly, seizure frequency in patients with LGG was remarkably reduced after 6-month TMZ therapy, which was also "an independent prognostic factor for progression-free survival and overall survival",1 indicating associations between seizure reduction and tumor response. However, no significant objective responses were detected on MRI in patients with and without seizure reduction.1 We offered an alternative explanation for this paradox.
Tumor progression of LGG was composed of at least two types, recurrence and malignant degeneration, with definitions of tumor recurrence or progressive growth on MRI for recurrence and either a significant increase in tumor contrast enhancement and/or malignant degeneration of a histological diagnosis for malignant degeneration, respectively.2 Regarding on the latter scenario, driver mutations of recurrent tumor were usually distinct from those of the initial ones, and nearly 50% of the mutations in the initial LGG were undetected in the same patient at recurrence, which occurred in 43% of all patients consecutively suffering from initial LGG and malignant degeneration. 3With an exomes sequence study of 23 objects who underwent both initial LGG and malignant degeneration, Johnson and colleagues3 demonstrated that patient receiving TMZ treatment had an incredible increase in mutations from 0.2 to 4.5 per megabase (Mb) at up-front to 31.9 to 90.9 per Mb at recurrence. The TMZ- induced hypermutations covered many tumor driver mutations, including dysregulation of RB and activation of AKT-mTOR signaling pathways.3 Recently, AKT-mTOR signaling pathway was reported to be involved in the controlling of epileptogenesis, and mTOR inhibition might contribute to antiseizure and antiepileptogenic effect in the WAG/Rij rat model.4 In terms of TMZ initiation either LGG up-front or at tumor progression in Koekkoek and colleagues's study 1, the underlying molecular signal pathways could be of significant heterogeneity, which may imply inherent differences in seizure frequency. Furthermore, although there were 21 out of 26 second histological diagnosis of malignant transformation before TMZ initiation2, there was no declaration of progression type distribution in each cohort. Let alone the declared absences of the relative molecular markers in the final diagnosis. In summary, these little flaws made such beautiful study kinds of imperfect.
Therefore, we suggest that the confounding role of malignant degeneration should be clarified in the elegant work described by Koekkoek and colleagues, which showed beneficial effects of TMZ on reduction of seizure frequency after LGG1.
1. Koekkoek JA, Dirven L, Heimans JJ, et al. Seizure reduction in a low-grade glioma: more than a beneficial side effect of temozolomide. J Neurol Neurosurg Psychiatry 2014;0:1-8.doi:10.1136/jnnp-2014-308136
2. Chaichana KL, McGirt MJ, Laterra J, et al. Recurrence and malignant degeneration after resection of adult hemispheric low-grade gliomas. J Neurosurg 2010;112:10-17.
3. Johnson BE, Mazor T, Hong C, et al. Mutational analysis reveals the origin and therapy-driven evolution of recurrent glioma. Science 2014;343:189-193.
4. Russo E, Andreozzi F, Iuliano R, et al. Early molecular and behavioral response to lipopolysaccharide in the WAG/Rij rat model of absence epilepsy and depressive-like behavior, involves interplay between AMPK, AKT/mTOR pathways and neuroinflammatory cytokine release. Brain Behav Immun 2014; http://dx.doi.org/10.1016/j.bbi.2014.06.016
Conflict of Interest:
Serial electrophysiology in Guillain-Barre syndrome: how crucial and of how much clinical relevance?
We thank Kokubun et al. , for their interest in our study. First, as we stated in our paper , our new proposed criteria provided, with a single study, globally, similar proportions and diagnostic shifts, to those found with older criteria and serial studies [3, 4]. There could be no indication from our study that in each and every single individual patient, similar diagnoses would be reached.
Uncini et al. have however very recently, in a editorial on our paper in this journal, reported the results of the application of our criteria to their cohort of 55 patients . This provided an albeit retrospective, validation of our criteria in another European population. They precisely used as gold-standard the serial studies available to them. For acute inflammatory demyelinating polyradiculoneuropathy (AIDP), they found that our criteria had a 70% sensitivity and 96% specificity with one study, versus 94% and 72% respectively obtained with Hadden et al.'s criteria . For axonal GBS, our criteria had a sensitivity of 81% and a specificity of 94% with one study, versus 47% and 100% respectively with Hadden et al.'s criteria. Hence, diagnostic accuracy was equivalent with our criteria to that of Hadden et al.'s criteria for AIDP (83.6% for both) and substantially higher with our criteria for axonal GBS (89.1% vs. 80%), considering a single electrophysiological evaluation.
Patient 1 presented by Kokubun et al. illustrates the superior accuracy of our criteria which allowed early identification of axonal GBS, with a single study, in keeping with the serological data provided. Kokubun et al.'s Patient 2, for her part, illustrates the fact that delayed appearance of electrophysiological abnormalities may, in a proportion of cases, result in late diagnostic confirmation of GBS subtype, irrespective of criteria utilized.
As we also mentioned in our paper, our analysis otherwise demonstrated a sensitivity of 91.3% for a definite, i.e. unequivocal, diagnosis of GBS, irrespective of subtype. This level of sensitivity is, for a diagnostic test in the acute setting of this disease, and in comparison to other neuropathies such as chronic inflammatory demyelinating polyneuropathy , very high, and unambiguously shows, the practical usefulness of electrophysiology with our criteria with a single test.
We are grateful to Kokubun et al. who state that our criteria may be more appropriate than previous criteria . We fully agree that in a minority of cases, accurate diagnosis of GBS subtype may require a repeat set of nerve conductions. However, how relevant this may be from a purely clinical and diagnostic perspective, weeks after onset and treatment, remains very debatable in our opinion, particularly given the high accuracy of our criteria for GBS subtype, already achieved with a single study.
1.Kokubun N, Nagashima T, Odamura M, Hirata K, Yuki N. Timing is crucial for electrodiagnosis of Guillain-Barré syndrome. J Neurol Neurosurg Psychiatry 2014, EPub before print.
2. Rajabally YA, Durand MC, Mitchell J, et al. Electrophysiological diagnosis of Guillain-Barré syndrome subtype: could a single study suffice? J Neurol Neurosurg Psychiatry 2014 May 9 EPub ahead of print.
3. Uncini A, Manzoli C, Notturno F, Capasso M. Pitfalls in electrodiagnosis of Guillain- Barré syndrome subtypes. J Neurol Neurosurg Psychiatry 2010;81:1157-1163.
4. Shahrizaila N, Goh KJ, Abdullah S, Kuppusamy R, Yuki N. Two sets of nerve conduction studies may suffice in reaching a reliable electrodiagnosis in Guillain-Barré syndrome. Clin Neurophysiol 2013;124:1456-1459.
5. Uncini A, Zappasodi F, Notturno F. Electrodiagnosis of GBS subtypes by a single study: not yet the squaring of the circle. J Neurol Neurosurg Psychiatry 2014 June 5 EPub ahead of print.
6. Hadden RD, Cornblath DR, Hughes RA, et al. Electrophysiological classification of Guillain-Barré syndrome: clinical associations and outcome. Ann Neurol 1998;44:780-788.
7. Rajabally YA, Nicolas G, Piéret F, et al. Validity of diagnostic criteria for chronic inflammatory demyelinating polyneuropathy: a multicentre European study. J Neurol Neurosurg Psychiatry 2009;80:1364- 1368.
Conflict of Interest:
Y.A.R. has received speaker/consultancy honoraria from LfB France, Griffols, and BPL and has received educational sponsorships from LfB France, CSL Behring and Baxter. G.N. has received deparmental research support/honoraria from Debiopharm, GSK, LfB France, Ipsen and Novartis.
Appropriate baseline setting for the evaluation of treatment
Troussiere et al. conducted an interesting survey to prevent the progress of Alzheimer's disease in patients with sleep apnoea syndrome (SAS) by continuous positive airway pressure (CPAP) therapy (1). I fundamentally agree with their study outcome. I have a query on the setting of CPAP and non-CPAP groups.
The cut-off point of 23 for Mini Mental State Examination (MMSE) is widely accepted. The authors mentioned that there was no significant difference in median value MMSE at baseline between two groups, but the max value of MMSE in 9 patients without treatment of CPAP was 24. On this point, I cannot ignore the 3.5 difference of median value. MMSE is one of the screening questionnaires and it reflects the progress of cognitive function in each patients.
Vos et al. investigated the prevalence and long-term outcome of preclinical Alzheimer's disease according to the following criteria: cognitively normal individuals with abnormal amyloid markers (stage 1), abnormal amyloid and neuronal injury markers (stage 2), or abnormal amyloid and neuronal injury markers and subtle cognitive changes (stage 3), by follow-up 311 participants, aged 65 or older, with clinical dementia rating of 0 (2). The 5-year progression rate to clinical dementia rating at least 0.5 was calculated, according to the baseline stages. As a result, a symptomatic Alzheimer's disease was 2% for participants classed as normal, 11% for stage 1, 26% for stage 2, and 56% for stage 3, respectively.
I suppose that baseline allocation of patients into CPAP and non-CPAP groups should be paid with caution, especially in MMSE. If not so, the net effect of CPAP treatment on the progress of cognitive function cannot determine. In addition, during the 3-year follow-up period, there is a possibility in the progress of preclinical Alzheimer's disease. I understand that SAS is not only the factor, but baseline setting is important to know the effect of CPAP therapy in patients with SAS for the progress of cognitive function.
I also recommend the authors to check the MMSE values more frequently during the 3-year follow-up study.
1 Troussiere AC, Monaca Charley C, Salleron J, et al. Treatment of sleep apnoea syndrome decreases cognitive decline in patients with Alzheimer's disease. J Neurol Neurosurg Psychiatry 2014 May 14. doi: 10.1136/jnnp-2013-307544
2 Vos SJ, Xiong C, Visser PJ, et al. Preclinical Alzheimer's disease and its outcome: a longitudinal cohort study. Lancet Neurol 2013;12:957- 65.
Conflict of Interest:
CT-negative, lumbar puncture-positive and CTA-negative patients have a low risk of aneurysms.
We are grateful to Bakker et al. for their prospective study in this area.
Two months prior to this, we published on the topic of CT-negative, lumbar puncture-positive and CT-angiography (CTA) negative patients. Such patients had been reported in 98 published cases. No causative aneurysms were found in neither these nor in the 9 cases which we identified.
Bakker et al report 37 additional patients in the section 'Imaging' on page 3 of their article. These 37 patients had digital subtraction angiography (DSA) within 48 hours and no vascular lesions were found. This brings the number of published cases to 144.
We recommend double-reporting of the CT angiogram in these apparently normal scans. The risk:benefit ratio of proceeding to DSA in such patients is debatable due to the relatively small number of published cases.
Arnab K. Rana[a], Helen E. Turner[b] and Kevin A. Deans[b]
a Aberdeen Biomedical Imaging Centre, University of Aberdeen, Lilian Sutton Building, Foresterhill, Aberdeen, AB25 2ZD, UK
b Department of Clinical Biochemistry, Aberdeen Royal Infirmary, Foresterhill, Aberdeen, AB25 2ZN, UK
 Bakker NA, Groen RJM, Foumani M et al. Appreciation of CT- negative, lumbar puncture-positive subarachnoid haemorrhage: risk factors for presence of aneurysms and diagnostic yield of imaging. J Neurol Neurosurg Psychiatry doi:10.1136/jnnp-2013-305955.
 Rana AK, Turner HE and Deans KA. Likelihood of aneurysmal subarachnoid haemorrhage in patients with normal unenhanced CT, CSF xanthochromia on spectrophotometry and negative CT angiography. J R Coll Physicans Edinburgh 2013; 43: 200-6.
Conflict of Interest:
Screening for post-stroke depression: caution for meta-analysis
Meader et al. reported screening abilities of several tools for detecting post-stroke depression by meta-analysis procedures (1). Although the Center of Epidemiological Studies-Depression Scale (CESD), the Hamilton Depression Rating Scale (HDRS) and the Patient Health Questionnaire (PHQ)-9 showed acceptable validity for screening of depression, these tools are not acceptable for clinical use for case- finding. In their article, the authors selected 23 cross-sectional studies and one prospective cohort study, and Hierarchical Summary Receiver Operating Curve (HSROC) meta-analyses were conducted to obtain pooled estimates of sensitivity and specificity and HSROC curves with a minimum of three studies to ensure stable estimates were computed. I think that their statistical procedure is fundamentally adequate, but some concerns are existed. First, there are no available diagnostic criteria specifically for post- stroke depression, and the reference standard for the diagnosis of depression was based on Diagnostic and Statistical Manual-Fourth Edition (DSM-IV) or the International Classification of Disease Tenth Edition (ICD -10) criteria. I suppose that ROC analysis without established reference standard for the diagnosis of depression should be handled with caution. Second, the authors included a one-year cohort study by Kang-et al. (2) for their meta-analysis. To keep sample size of pooled data, inclusion of this cohort study is not a mistake. To specify the change of effect, sensitivity analysis by excluding cohort study should also be conducted for their study. Finally, I speculate the existence of ethnic difference and social development on the screening ability for post-stroke depression. Unfortunately, there is no way to adjust these variables in addition to sex and age, which are fundamental confounders on the risk of stroke. Anyway, diagnostic criteria for post-stroke depression should be urgently determined as the reference.
References 1 Meader N, Moe-Byrne T, Llewellyn A, et al. Screening for poststroke major depression: a meta-analysis of diagnostic validity studies. J Neurol Neurosurg Psychiatry 2014;85:198-206. 2 Kang HJ, Stewart R, Kim JM, et al. Comparative validity of depression assessment scales for screening poststroke depression. J Affect Disord 2013;147:186-91.
Conflict of Interest:
Response to research paper of Mr. WesselyThis letter was published in error. The text is no longer available.
Reply - We thank Prof Shubhakaran for the interest shown in our article and for highlighting that porphyric neuropathy should be among the differential diagnosis in patients presenting the pharyngeal-cervical- brachial weakness. Indeed, porphyric neuropathy does share some clinical features with Guillain-Barre syndrome and in 50% of cases weakness starts in the upper limbs and therefore may mimic pharyngeal-cervical-brachial weakness. Similar to Guillain-Barre syndrome, progression to nadir occurs by 4 weeks, although in some cases development of tetraparesis and respiratory failure can be rapid. Cerebrospinal fluid may also show albuminocytological dissociation. Similar to pharyngeal-cervical-brachial weakness, nerve conduction studies show axonal-type neuropathy. Porphyric neuropathy, however, is rare and patients invariably complain of severe abdominal pain and develop psychiatric symptoms before developing neuropathy. Neuropathy, when is does occur is usually asymmetric with prominent autonomic involvement, which differentiates it from Guillain- Barre syndrome and indeed pharyngeal-cervical-brachial weakness in most cases. Reference: Albers J W, Fink J K. Porphyric neuropathy. Muscle Nerve. 2004; 30, 410-22.
Conflict of Interest:
Re:Levodopa equivalent daily dose and the development of impulse control disorder
Thank you very much for your interest in our paper and your comments. We have used the levodopa equivalent daily dose (LEDD) of dopamine agonist (ADA) as previously published, and must agree with you as the topic probably needs a thorough review. Anyway, it seems that the occurrence of impulse control disorders (ICDs) in patients with Parkinson's disease (PD) and other diseases in treatment with DA is not just dose-dependent. It is clear that the higher the dose the more prevalent ICDs, but lower doses can also precipitate them (Perez-Lloret et al., 2012; Weintraub et al., 2010). We did not find differences regarding LEDD of rotigotine between PD patients with or without ICD. We may regard this phenomenon as a class effect of rotigotine, as far as we know idiosyncratic, which may imply a pathoplastic effect, as it would change the clinical spectra of the disease.
Conflict of Interest:
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