eLetters

626 e-Letters

  • Issues on factors and propensity score matching in the study of achieving the treatment target in generalised myasthenia gravis

    We appreciate the author for exploring the independent factors associated with the achievement of the treatment target (MM and MM5mg) in generalized myasthenia gravis (MG) patients, including early fast-acting treatment (EFT) [1]. This study attempted to include patients treated with EFT or non-EFT by propensity score (PS) matching to obtain a balance in baseline characters between the two groups, and to determine whether EFT was an independent factor of achieving MM5mg the treatment target by adjusting the confounding factors. The primary endpoint of this study was to reach MM5mg, and Cox regression analysis was used to explore the independent factors. Some concerns are raised here for discussion with the authors.
    1. Is the starting point of the study from the beginning of immunotherapy? If so, pre-treatment factors such as gender, onset age, pre-treatment disease duration, pre-treatment worst severity, subtype, and severity at the start of treatment, need to be included. Ongoing treatment factors should include at least the dose range and duration of oral prednisone, Calcineurin inhibitors usage and intervals between their initiation time and the beginning of immunotherapy, and the number of cycles of fast-acting therapies administered 6 months after initiation of immunotherapy. All of these factors may affect the prognosis. We also wish to know whether the thymectomy was performed before or after the initiation of immunotherapy in each patient, and the interva...

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  • Important points that should be considered when assessing the treatment patterns for spasticity in patients with multiple sclerosis

    Dr Smith and his colleagues have recently written an article entitled “Spasticity treatment patterns among people with multiple sclerosis: a Swedish cohort study” which was published in Journal of Neurology, Neurosurgery and Psychiatry in December 23, 2022 (1). The authors conducted a population-based cohort study containing details of 5345 patients with multiple sclerosis (MS) with a follow-up duration of about ten years to assess the prevalence and pattern of medications used by these patients for spasticity and factors associated with them. The study showed that near to 10 percents of patients with incident MS and 19 percents of those with prevalent MS received baclofen. The use of baclofen was higher among patients with higher Expanded Disability Severity Scores and younger individuals. Besides, the study showed that the rate of discontinuation of baclofen as high. The study provides strong evidence on the pattern of treatment in these patients with a proper population size and long follow-up duration; there are, however, concern that I would like to mention.
    First, the authors did not consider all treatment types for spasticity. The medications included in the study were baclofen, diazepam, clonazepam, gabapentin and cannaboids. In a nationwide study of individuals who received pharmacologic treatment for spasticity in Sweden, the same country as the current study on MS patients was conducted in, the mean proportion of use of botulinum toxin was 9.2% with percen...

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  • Early treatment start versus late treatment start should have been defined more accurately

    To the Editor
    I have read the work conducted by Dr. He et al. on importance of early treatment of patients with multiple sclerosis and its association with outcomes reported by the patients (1). The work entitled “Association between early treatment of multiple sclerosis and patient-reported outcomes: a nationwide observational cohort study” was first published in Journal of Neurology, Neurosurgery and Psychiatry in 7th of December, 2022. This observational study showed that earlier initiation of treatment with disease-modifying treatment in the patients with multiple sclerosis was statistically significantly associated with patient-reported physical symptoms. There are some points that I thought were uncertain and unclear in the study.
    The study used a cutoff of two years to divide the participants into two groups of early treated patients who were those whose treatment was initiated within two years from the onset of the disease and late treated patients with treatment initiation between two and four years after onset. The authors justified that this classification was based on the guideline recommended by international committees advocating the initiation of disease modifying treatment in less than 12 months; however, it is not clear how this recommendation support the cutoff used in the study. In previous similar studies, a cutoff value of 6 months was mainly considered (2-4). Furthermore, it would have been better if the authors also had reported the time...

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  • Caution required when interpreting the risk of MND.

    Russell et al report on the risk of neurodegenerative disease (a composite outcome including dementia, motor neuron disease (MND) and Parkinson’s disease) among former international rugby union players. Using a matched retrospective cohort design they show not only that the rugby players group had two and half times the risk of developing neurodegenerative disease, they were also more likely to die from, be hospitalised due to, or be prescribed drugs related to neurodegenerative diseases. These are important findings.

    The risks for Dementia, Parkinson’s disease and MND are also estimated. It is regrettable that many media outlets (The Times, Independent, Mirror, Irish Times and the Guardian to name but a few) have focused on the secondary motor neuron disease outcome, with its odds ratio point estimate of around 15, given the considerable uncertainty attached to this figure (95% confidence interval 2.10 to 178.96). Although the other outcomes have more events, and are consequently more likely to be robust, attention has been drawn to the most eye-catching 'risk' figure, even though this is not one of the primary findings of the paper.

    What seems to be missing from this report is information about how many players were diagnosed with MND, or what these findings mean in terms of the absolute risk. The authors do not report how many people had MND in the rugby group, but they do say "In the analysis of MND/ALS, zero events were recorded among the...

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  • Personal goal attainment: a different approach to evaluating outcomes

    The authors say their intervention did not improve independence in activities of daily living for people with dementia as measured by the BADLS. In this context they do not mention their work showing that participants improved in functional ability on their chosen personal goals.[1] Using data from 7 of 10 trial sites and devising a goal attainment scaling method to evaluate 266 goals set by 111 participating dyads, results ‘strongly suggested’ that participants improved on their individual goals.

    This fits with the emerging pattern of findings from personalised rehabilitative interventions that aim to support functioning and self-management in the early stages of dementia. Positive outcomes in personal goal attainment have been demonstrated in several large trials which are not mentioned in the discussion of this paper, for example GREAT[2] and REDALI-DEM.[3] However, none of the large trials of cognitive rehabilitation or related approaches has reported improvements on general measures of functional ability or other secondary outcomes, although some significant effects have been seen in smaller trials.[4,5]

    The DESCANT intervention may have had several limitations, including short duration, limited number of sessions, manualised delivery by practitioners who are not qualified health professionals, and limited scope in the choice of goals, aids, and strategies. The focus of the intervention is unlikely to have influenced many domains covered by the BADLS (e...

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  • Doxycycline use, duration and side effect

    Doxycycline is an important drug used in many disease conditions like Brucellosis, Lyme disease, malaria etc. One important side effect with it's use is raised intracranial pressure i.e. idiopathic intracranial pressure. So this study is a nice development as lesser duration of treatment will reduce cost of therapy, and a psychological well being because of less drug, less duration and less cost.
    References-
    1. J Lochhead, and J S Elston.Doxycycline induced intracranial hypertension BMJ. 2003 Mar 22; 326(7390): 641–642.
    doi: 10.1136/bmj.326.7390.641.

  • Concerns regarding methodology in the purview of definitions and reference intervals

    The research study conducted by Ward et al., [1] has effectively marked an understandable association between frailty, lifestyle and genetics as factors of dementia in adults aged 60 and above. The findings of this study could potentially have major implications in the field of neuropsychiatric research in the field of geriatric studies.

    One of the concerns regarding the methodology of classification of a healthy lifestyle score was that participants who were currently non-smokers were identified as a valid classification in the healthy subgroup. This is questionable due to the fact that, for this classification, no reference was cited to accept non current smokers as a valid factor in the healthy lifestyle score. According to several studies, smoking was indicated as one of the major risk factors for dementia among the elderly. [2] A 2019 Lancet commission identified that smoking was the third among nine modifiable risk factors for dementia. Furthermore a review of 37 studies in the field of association of smoking as a risk factor for dementia identified that compared to never smokers, smokers had a 30% higher chance of developing dementia in general along with a 40% higher chance of developing Alzheimers. [3] So to associate non-current smokers into a healthy lifestyle category is concerning but instead, the classification should have been rather as never-smokers and smokers (both current and non-current). An appropriate classification of smokers and non-smokers...

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  • Frailty, genetics, and dementia risk: why stop at lifestyle?

    Ward et al.'s recent study on frailty, lifestyle, genetics and dementia risk (1) is a major contribution to the growing multimorbidity approach towards dementia. But it is not clear why the authors exclusively frame their discussion on practical steps to reduce dementia risk around healthy lifestyle. They paradoxically argue that "adherence to national guidelines for healthy lifestyle behaviours is central to dementia risk reduction recommendations," while also recognising that multi-domain lifestyle interventions have a weak evidence base in favour of them. An exclusive focus on lifestyle to achieve reduction of frailty and dementia overlooks social gradients of health, particularly the unequal distribution of access to the kind of safe and stimulating living and working environments in which risk reduction can take place through high-quality stimulation and the absence of stressors like noise and air pollution (2). The authors make no mention of social determinants. People with higher income are more likely to part in lifestyle interventions (3), and focusing exclusively on conscious behavioural change to achieve dementia risk reduction may therefore worsen inequalities in dementia risk (4). Therefore, to address not only dementia risk reduction but also the reduction of health inequities, as well as promoting lifestyle changes, the research community ought to stress the need for action against the social determinants of frailty and dementia (5).

    Re...

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  • Re: Frailty, lifestyle, genetics and dementia risk

    Ward et al. reported the relationships between frailty index, healthy lifestyle and polygenic risk scores, and incident all-cause dementia (1). The adjusted hazard ratio (HR) (95% CI) of participants with high frailty for incident dementia was 3.68 (3.11 to 4.35). In addition, the adjusted HR (95% CI) of participants with high genetic risk and high frailty for incident dementia was 5.81 (4.01 to 8.42).The authors emphasized of controlling frailty for dementia prevention strategies, even among subjects at high genetic risk. I have two comments about their study.

    First, Lourida et al. investigated the association between healthy lifestyles and risk of dementia by considering genetic risk (2). The adjusted HR (95% CI) of participants with high genetic risk and unfavorable lifestyle for incident dementia was 2.83 (2.09 to 3.83). In addition, a favorable lifestyle was associated with a lower dementia risk among participants with high genetic risk. There was no significant interaction between genetic risk and lifestyle factors, and I suppose that unfavorable lifestyles and genetic factors independently contribute to the risk of dementia. The level of frailty may be related to lifestyles and contribute to subsequent progression of cognitive impairment.

    Second, Kojima et al. conducted a meta-analysis regarding the effect of frailty on the incident dementia among community-dwelling older people (3). Th pooled HRs (95% CIs) of frailty for the incident Alzheimer disease...

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  • Ophthalmoplegia, sensorineural hearing loss, and bilateral vestibulopathy secondary to presumed VEXAS-related polycranial neuritis

    We read with interest the letter by Bert-Marcaz et al., reporting on a 74-year-old man with vacuole, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome and chronic inflammatory demyelinating polyneuropathy [1]. We agree with the authors’ postulation that the simultaneous onset of the two diseases suggests a potentially causal link between VEXAS and the demyelinating abnormalities they observed on nerve conduction studies and nerve biopsy. We have previously reported a case of a 68-year-old man with VEXAS associated with neurological features, including ophthalmoplegia, sensorineural hearing loss and bilateral vestibulopathy [2]. Our hypothesis for the mechanism of neurological involvement was polycranial neuritis, given that there was no evidence of orbital inflammation on MRI and there was significant improvement with corticosteroids. Neurologists should consider the diagnosis of VEXAS (and other autoinflammatory syndromes of innate immunity) in patients with neurological problems who have (i) unexplained fever and elevated acute phase reactants, especially when there is a remitting and relapsing course, (ii) unexplained multisystem disease, and (iii) no evidence of infection, malignancy or autoimmune (i.e., antibody-mediated) disease.

    References:
    [1] Bert-Marcaz C, Briantais A, Faucher B, Corazza G, Ebbo M, Attarian S, Delmont E, Fortanier E. Expanding the spectrum of VEXAS syndrome: association with acute-onset CIDP. J Neurol Neurosurg Psychiat...

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