eLetters

616 e-Letters

  • Response to: COVID-19 associated Myasthenic crisis

    We would like to thank the author for pointing out the fact that a proper disease control in myasthenia gravis (MG) probably predicts a favourable outcome during SARS-CoV-2 infection.
    MG exacerbation was only observed in one patient (case 1) treated successfully with immunoglobulins (IVIG) as described. No MG crisis was reported during this period in non-infected patients.
    None of the four patients described in our case report received COVID-19 related treatment, namely antiviral and/or hydroxychloroquine. Case 4 received antibiotherapy for 5 days (azythromicine and tazobactam).
    Regarding case 2, this patient presents with recurring symptoms of fever and shortness of breath since March 2020. In this regard a chest CT and repeated D-dimers were performed in October, showing negative results.

  • Chronic inflammatory axonal polyneuropathy

    In clinical practice, neuropathies are groups of disorders with curable, treatable, and non-treatable aetiologies, the later accounting for most of the cases.[1] Every newly identified disorder either on the basis of etiology or syndromic group responding to particular treatment brings hope for few more patients.
    This study by Shin J Oh et al [2] brings hope for some patients who were previously either classified as axonal neuropathy of undetermined cause orin the evolutionary phase of a neurodegenerative diseases (such as anterior horn cell diseases). Thus, in the absence of any evidence, such patients usually remained deprived of any immunotherapies and succumbed to the progressive disease. Now with this piece of information, it can be inferred that all those patients presenting with chronic (more than 2 months), symmetrical or asymmetrical, proximal and distal weakness without any evidence of demyelination (i.e. axonal) on nerve conduction studies and without any known secondary causes of axonal polyneuropathy could qualify for immunotherapy when nerve biopsy or CSF protein > 55 mg/dl shows evidence of inflammation. Thus, chronic inflammatory polyneuropathy syndrome would be a more apt diagnosis with two variants: demyelinating (usual Chronic inflammatory demyelinating polyneuropathy, CIDP) and axonal, much like Guillain-Barre syndrome.
    However, it can be noted that all the patients included in the study did not qualify for CIAP. There were six patients w...

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  • Guillain-Barré syndrome and COVID-19: an observational multicentre study from two Italian hotspot regions; response to Keddie et al.

    We read with interest the comments of Keddie and Colleagues who suggested caution in accepting a causation link between SARS-CoV-2 infection and Guillain-Barré syndrome (GBS) and in interpreting results from our study “Guillain-Barrè syndrome and COVID-19: an observational multicentre study from two Italian hotspot regions" (1).
    We believe they have misinterpreted the message of our paper and have drawn conclusions that was not our intention to draw.
    Their first consideration is that our paper cannot demonstrate a causation link between COVID-19 and GBS. Of course, we agree. In fact, we did not talk about any causal nexus. It is well known that, in statistics, “causation” indicates a relationship between two events where one event is affected by the other. In order to demonstrate “causation”, prospective studies are needed. Our study is based on retrospective findings and identified an increased rate of GBS cases concomitantly with the COVID-19 spread in our regions. On this basis, we could not (and indeed we did not) conclude for a definite causative relationship but we suggested a pathogenic link for which COVID-19 could represent a trigger for GBS, as already suggested by other authors (2).
    Keddie et al. claimed some possible methodological biases. Part of them is obviously related to the retrospective nature of the study and have been listed as limitations of the study at the end of our paper. They calculated the 95% confidence intervals of the...

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  • COVID-19 associated Myasthenic crisis

    We appreciate the authors for describing their patients’ data in myasthenia with COVID-19 which would help clinicians caring for such patients.1 We have the following comments and queries. We would like to point out that, three out of the four patients who had SARS-CoV-2 infection were not having any infiltrates on chest x-ray, suggesting that these patients had mild COVID-19 infection.2 It is also noteworthy that all these patients who had a normal chest radiograph were either on very low dose azathioprine or no immunosuppressant apart from low dose steroids. As the authors rightly point out, the myasthenia disease activity prior to infection with SARS-CoV-2 is an important predictor of the severity of the myasthenic crisis. It is possible that patients with better control of symptoms or those on appropriate immunosuppression don’t develop a crisis with mild COVID-19. Secondly, it would be interesting to know what specific therapy for COVID-19 was offered to these patients. It is possible that steroids given as a part of therapy for COVID-19 could also act to stabilize disease activity in myasthenia. Similarly, IVIg given to manage Myasthenic crisis could have prevented progression in the severity of COVID-19. Likewise, myasthenic patients who receive drugs such as hydroxychloroquine and macrolides can have precipitation of myasthenic crisis.3,4 In case 2, we would also be interested to know if other causes of chest pain and breathlessness like pulmonary thromboembolism w...

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  • Further research required to support a causative association between GBS and COVID-19

    To the Editor

    We were interested to read the study of Filosto et al [1] concluding a significant link between Guillain-Barre Syndrome (GBS) and COVID-19 infection in Northern Italy at the peak of the 1st wave SARS-CoV2 pandemic. We urge caution in accepting such a causative conclusion using a retrospective observational study; causation is not conclusively proven and is drawn from potentially biased data and small case numbers of a rare condition, and a rate calculation without confidence intervals to infer uncertainty.

    Only 34 cases of GBS, of whom 30 were COVID-19 positive, are reported over a 2-month period, with a denominator population of 8,400,107. We calculated the 95% confidence intervals of the incidence rates as 0.08 per 100,000 per month (95% C.I.: 0.04-0.15) in 2019 and 0.2 per 100,000 per month (95% C.I.: 0.14-0.28) in 2020. The overlapping confidence intervals do not support a statistically significant increase in GBS rates from 2019 to 2020. Furthermore, the simple multiplication of the monthly rate by 12 to create an approximate annualised incidence potentially amplifies the inaccuracy. We suggest that the 2.6-fold difference in GBS incidence from 2019 to 2019 is prone to meaningful statistical error.

    During the initial stages of the pandemic the denominator of COVID-19 positive cases will have been under-reported because testing was limited to the symptomatic and presenting populations. We are told that 62,679 inhabitants of the regi...

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  • Vibration therapy for Parkinson's disease: another lesson from Charcot

    We read with great interest the article by Macerollo et al. entitled “Non-invasive intervention for motor signs of Parkinson’s Disease: the effect of vibratory stimuli.”[1] The authors evaluated the use of a wearable device called the "Emma Watch" that produces a constant vibratory stimulus (200 Hz) to the wrist with frequencies of 20 bpm or 60 bpm in terms of motor function of the arms of 16 patients with Parkinson’s disease (PD).[1] Motor performance was assessed through three different tasks: a nine-peg hole test, a STYAR tracing task, and a SPIRAL tracking test.[1] The authors found that patients with PD who used the device with 200 Hz peripheral vibration modulated by 60 bpm as they carried out these tasks performed better in terms of speed and precision.[1] The final conclusion was that vibrotactile stimulation can improve motor function in patients with PD.[1] It is important to comment that the authors did not discuss their results in terms of other studies in the literature, including one systematic review published in 2014 [2] and another with a meta-analysis published in 2020. [3] In these studies, vibratory stimulation in patients with PD was generally seen to yield positive results with regard to balance and gait. [2,3] From a historical point of view, the pioneering and seminal work of Jean-Martin Charcot, who used a vibrating chair to treat patients with PD, should also be noted.[4,5]

    1. Macerollo A, Holz C, Cletheror D, et al. Non-invasiv...

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  • Large data, but what is the implication comparing the aneurysm discovered by bleeding and those by other reasons?

    Dear editor,
    We read with great interest the article by Rousseau et al. “Location of intracranial aneurysms is the main factor associated with rupture in the ICAN population.”1
    They compared ruptured intracranial aneurysms (RIAs) with unruptured cerebral aneurysms (UCAs) in the ICAN registry, and analyzed factors that were considered associated with subarachnoid hemorrhage in previous literature. As a result, they found the location of the aneurysm showed the largest hazard ratio as much as 6.05 and showed their result with beautiful info-graphic.
    We should be careful that their result is derived from comparisons between the aneurysms, which caused subarachnoid hemorrhage and UCAs that was found without bleeding. Hence, the meaning is different from that of ISUIA2, UCAS Japan3, and other studies, which investigated the risk of bleeding from the known UCAs. As noted in the discussion of the headache, which prefers UCAs to RIAs, the factors examined may be seeing factors, which lead to brain examination without causing subarachnoid hemorrhage in France.
    As in the title, they focused on the location of the aneurysm, and found ACA and posterior circulation aneurysms have high odds ratio of 4.99 and 6.05 respectively comparing with ICA aneurysms. As in ISUIA study, they included internal carotid- posterior communicating artery (IC-Pcom) aneurysms in the posterior circulation aneurysms, and “ICA” includes other aneurysms occurring on the ICA. However...

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  • Parkinson's disease determinants, prediction and gene-environment interactions

    Jacobs et al. investigated the association of environmental factors and prodromal features with incident Parkinson's disease (PD) with special reference to the interaction of genetic factors [1]. The authors constructed polygenic risk scores (PRSs) for the risk assessment. Family history of PD, family history of dementia, non-smoking, low alcohol consumption, depression, daytime somnolence, epilepsy and earlier menarche were selected as PD risk factors. The adjusted odds ratio (OR) (95% confidence interval [CI]) of the highest 10% of PRSs for the risk of PD was 3.37 (2.41 to 4.70). I have some concerns about their study.

    Regarding risk/protective factors of PD, Daniele et al. conducted a case-control study to performed a simultaneous evaluation of potential factors of PD [2]. Among 31 environmental and lifestyle factors, 9 factors were extracted by multivariate analysis. The adjusted OR (95% CI) of coffee consumption, smoking, physical activity, family history of PD, dyspepsia, exposure to pesticides, metals, and general anesthesia were 0.6 (0.4-0.9), 0.7 (0.6-0.9), 0.8 (0.7-0.9), 3.2 (2.2- 4.8), 1.8 (1.3-2.4), 2.3 (1.3- 4.2), 5.6 (2.3-13.7), 2.8 (1.5-5.4), and 6.1 (2.9-12.7), respectively. Family history of PD and non-smoking were common risk factors, which had also been reported by several prospective studies.

    Regarding smoking, Angelopoulou et al. investigated the association between environmental factors and PD subtypes (early-onset, mid-and-late on...

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  • Pain Responsiveness: A Useful Clinical Tool?

    The recently published paper ‘Abnormal pain perception is associated with thalamo-cortico-striatal atrophy in C9orf72 expansion carriers in the GENFI cohort’ by Convery et al.[1] draws attention to a topic of great importance in the field of frontotemporal dementia (FTD) research. In this study, Convery and colleagues investigated differences in pain responsiveness within a group of patients with genetic FTD. Changes in pain responsiveness compared to baseline were captured using a scale designed by the group, and patients were scored from 0-3 (0 = no change, 0.5 = questionable or very mild change, 1 = mild change, 2 = moderate change, 3 = severe change). Within the sample, symptomatic C9orf72 mutation carriers (9/31) experienced greater changes in pain responsiveness than symptomatic MAPT (1/10) and GRN (1/24) mutation-carriers or normal controls (1/181). Within the C9orf72 mutation carriers, these changes were associated with thalamo-cortico-striatal atrophy.
    This research brings attention to an important but little-investigated clinical feature of FTD. Changes in pain responsiveness, including both increases and decreases, have now been reported in both sporadic and genetic FTD, along with other somatic complaints.[1–4] However, the changes are not widely captured in either clinical or research settings, and the field lacks standardized and objective measurements to do so. The ability to measure changes in pain responsiveness may be a useful clinical marker to di...

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  • Reply to: Mental health and suicide in former professional soccer players

    We thank White and colleagues for their correspondence on our article(1) and note many of the observations raised are already addressed by our robust study design and discussed in the original manuscript text. Importantly, we are quite clear throughout that this is a study designed to investigate whether there is higher risk of common mental health disorder in former professional soccer players than anticipated from general population controls.

    Undoubtedly, there will be physically active individuals in our general population control group, including a number who might have participated in some form of contact sport. However, we would suggest this does not define our over 23,000 matched general population controls as a cohort of ‘non-elite’ athletes, as proposed by White et al. Instead, we would assert this merely underlines their legitimacy as a general population control cohort for comparison with our cohort of almost 8000 former professional soccer players.

    Potential study limitations regarding healthy worker effect, illness behavior in former professional soccer players and use of hospitalization datasets are addressed in detail in our manuscript text. Regarding data on duration of hospital stay and therapy, while these might indeed be of interest in follow-on studies regarding illness severity, we would suggest that they are not immediately relevant to a study designed to address risk of common mental health disorder.

    As White et al observe, wh...

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