We are writing to respectfully offer some additional comments on the recent publication of Hannaway et al. in JNNP titled “Visual dysfunction is a better predictor than retinal thickness for dementia in Parkinson’s disease”.
While the authors provided interesting insights on the predictive value of higher order visual functions for dementia, we noticed that the authors did not find significant associations between parafoveal GCIPL (pfGCIPL) and cognition in their work, whereas our research did. As they mentioned, the range of cognitive impairment was higher in our sample, and possibly this might have driven our findings. However, we would like to add that the relationship between the retina and cognition is not linear, according to our data. As such, we calculated relative risks by categorizing continuous variables, which allowed us to identify non-linear relationships between pfGCIPL and cognitive impairment. Furthermore, we speculate that these variables do not exhibit a synchronous pattern of change over time, suggesting that the temporal trends are not closely linked, which might justify the lack of association in the current work.
We do agree with the authors in that visual function is a good predictor of cognitive deterioration. Our previous work also demonstrated this fact, but we would like to highlight the benefits of retinal OCT imaging in this context, if its utility is validated. Retinal OCT imaging is a faster and easier-to-measure technique com...
We are writing to respectfully offer some additional comments on the recent publication of Hannaway et al. in JNNP titled “Visual dysfunction is a better predictor than retinal thickness for dementia in Parkinson’s disease”.
While the authors provided interesting insights on the predictive value of higher order visual functions for dementia, we noticed that the authors did not find significant associations between parafoveal GCIPL (pfGCIPL) and cognition in their work, whereas our research did. As they mentioned, the range of cognitive impairment was higher in our sample, and possibly this might have driven our findings. However, we would like to add that the relationship between the retina and cognition is not linear, according to our data. As such, we calculated relative risks by categorizing continuous variables, which allowed us to identify non-linear relationships between pfGCIPL and cognitive impairment. Furthermore, we speculate that these variables do not exhibit a synchronous pattern of change over time, suggesting that the temporal trends are not closely linked, which might justify the lack of association in the current work.
We do agree with the authors in that visual function is a good predictor of cognitive deterioration. Our previous work also demonstrated this fact, but we would like to highlight the benefits of retinal OCT imaging in this context, if its utility is validated. Retinal OCT imaging is a faster and easier-to-measure technique compared to measuring visual functions. Moreover, OCTs are widely available in most ophthalmology departments, and this accessibility makes it a practical tool for assessing cognitive impairment and predicting dementia risk, particularly in primary care settings where time and resources are often limited. Furthermore, OCT might be also useful to be incorporated in clinical trials of disease-modifying therapies, as it allows objective, reliable and quantitative measurements of retinal parameters. All these advantages make it imperative to explore and better understand the temporal relationship between the retina and cognition.
We would like to address some final points that were discussed in the paper to provide further clarification. In our work, we included carriers with E46K mutation in the SNCA gene, not GBA gene. Also, the authors state that it is not clear whether model that tested the association between baseline pfGCIPL thickness and the risk of cognitive decline in idiopathic PD was adjusted for age. In fact, the model was adjusted for age, but also for disease duration, sex and levodopa equivalent daily dose.
To conclude, we are grateful for the valuable insights provided by the authors about the usefulness of the retina for cognitive monitoring. Moving forward, we remain committed to further exploring and elucidating this fascinating area of research, and we share the authors' enthusiasm for advancing our knowledge on the temporal dynamics of the retinal structure and its relationship with cognitive processes.
Ayton et al. reported the association between ferritin, apolipoprotein E (APOE) and dementia-related biomarkers such as amyloid β42/total-tau and phosphorylated tau181 (p-tau181) in cerebrospinal fluid (CSF) (1). CSF ferritin and APOE were positively associated with p-tau181, which was most predominant in subjects without increase in amyloid β42/total-tau. I present information about the study.
Pan et al. investigated the associations of CSF ferritin and CSF biomarkers of Alzheimer's disease (AD) (2). They found that CSF ferritin increased in subjects with more advanced categories of CSF biomarkers such as amyloid β42 and p-pau, although there were stronger relationships of CSF ferritin with p-tau and t-tau, rather than amyloid β42. This means that biological action of ferritin in the brain for AD may be more closely related to tau protein.
Baringer et al. described brain iron homeostasis in Alzheimer's disease, Parkinson's disease, and other neurodegenerative diseases (3). They emphasized that endothelial cells of the blood-brain barrier were the site of iron transport regulation, and iron uptake, transcytosis, and release were mainly conducted. By controlling the excess of brain iron, neurodegenerative disorders may be improved. The mechanism that tau protein spreads through functionally connected neurons in Alzheimer's disease have been precisely reported (4), and it may be related to the excess of brain iron storage.
Ayton et al. reported the association between ferritin, apolipoprotein E (APOE) and dementia-related biomarkers such as amyloid β42/total-tau and phosphorylated tau181 (p-tau181) in cerebrospinal fluid (CSF) (1). CSF ferritin and APOE were positively associated with p-tau181, which was most predominant in subjects without increase in amyloid β42/total-tau. I present information about the study.
Pan et al. investigated the associations of CSF ferritin and CSF biomarkers of Alzheimer's disease (AD) (2). They found that CSF ferritin increased in subjects with more advanced categories of CSF biomarkers such as amyloid β42 and p-pau, although there were stronger relationships of CSF ferritin with p-tau and t-tau, rather than amyloid β42. This means that biological action of ferritin in the brain for AD may be more closely related to tau protein.
Baringer et al. described brain iron homeostasis in Alzheimer's disease, Parkinson's disease, and other neurodegenerative diseases (3). They emphasized that endothelial cells of the blood-brain barrier were the site of iron transport regulation, and iron uptake, transcytosis, and release were mainly conducted. By controlling the excess of brain iron, neurodegenerative disorders may be improved. The mechanism that tau protein spreads through functionally connected neurons in Alzheimer's disease have been precisely reported (4), and it may be related to the excess of brain iron storage.
References
1. Ayton S, Janelidze S, Kalinowski P, et al. CSF ferritin in the clinicopathological progression of Alzheimer's disease and associations with APOE and inflammation biomarkers. J Neurol Neurosurg Psychiatry 2023;94(3):211-219.
2. Pan R, Luo S, Huang Q, et al. The associations of cerebrospinal fluid ferritin with neurodegeneration and neuroinflammation along the Alzheimer's Disease Continuum. J Alzheimers Dis 2022;88(3):1115-1125.
3. Baringer SL, Simpson IA, Connor JR. Brain iron acquisition: An overview of homeostatic regulation and disease dysregulation. J Neurochem 2023;165(5):625-642.
4. Schoonhoven DN, Coomans EM, Millán AP, et al. Tau protein spreads through functionally connected neurons in Alzheimer's disease: a combined MEG/PET study. Brain 2023. doi: 10.1093/brain/awad189
Åkerstedt et al. conducted a case-control study with 2075 cases and 3164 controls to investigate the association between sleep and risk of multiple sclerosis (MS) (1). Sleep duration, circadian disruption and sleep quality during adolescence were used for sleep variables. The authors calculated the adjusted OR with 95% CIs using logistic regression models, and short sleep (<7 hours/night) and low sleep quality were significantly associated with increased risk of developing MS. I have a question regarding the ways of multivariate analysis.
The ratio in the number of cases and controls is about 1.5 in this study. If the authors selected unconditional logistic regression analysis, OR might become conservative. If the authors selected conditional logistic regression analysis, the increased number of controls is preferable to make stable estimation. Instead of selecting a case-control study with a matching procedure, using all pooled data without a matching procedure can be selected for the analysis (2).
Anyway, a recall method has a possibility of including bias and risk assessment of MS with subjective sleep variables should be paid with caution.
References
1. Åkerstedt T, Olsson T, Alfredsson L, et al. Insufficient sleep during adolescence and risk of multiple sclerosis: results from a Swedish case-control study. J Neurol Neurosurg Psychiatry 2023;94(5):331-6.
2. Hamajima N, Hirose K, Inoue M, et al. Case-control studies: matched controls...
Åkerstedt et al. conducted a case-control study with 2075 cases and 3164 controls to investigate the association between sleep and risk of multiple sclerosis (MS) (1). Sleep duration, circadian disruption and sleep quality during adolescence were used for sleep variables. The authors calculated the adjusted OR with 95% CIs using logistic regression models, and short sleep (<7 hours/night) and low sleep quality were significantly associated with increased risk of developing MS. I have a question regarding the ways of multivariate analysis.
The ratio in the number of cases and controls is about 1.5 in this study. If the authors selected unconditional logistic regression analysis, OR might become conservative. If the authors selected conditional logistic regression analysis, the increased number of controls is preferable to make stable estimation. Instead of selecting a case-control study with a matching procedure, using all pooled data without a matching procedure can be selected for the analysis (2).
Anyway, a recall method has a possibility of including bias and risk assessment of MS with subjective sleep variables should be paid with caution.
References
1. Åkerstedt T, Olsson T, Alfredsson L, et al. Insufficient sleep during adolescence and risk of multiple sclerosis: results from a Swedish case-control study. J Neurol Neurosurg Psychiatry 2023;94(5):331-6.
2. Hamajima N, Hirose K, Inoue M, et al. Case-control studies: matched controls or all available controls? J Clin Epidemiol 1994;47(9):971-5.
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...
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 interval between the thymectomy and the first achievement of the treatment target.
2. In order to obtain a balance in clinical characters between EFT and non-EFT groups, PS matching was adopted in this study. The PS matching should be based not only on the factors that determined the choice of comparative treatments but also on the pre-treatment factors that might influence prognosis. The disease duration and severity at the start of treatment were not considered in the background factors provided in this study. More importantly, is the determination of EFT usage dependent on the factors acquired by the post hoc analysis of MM5mg achievement? Since the concept of EFT to achieve an early improvement and good prognosis gradually spread in Japan in the last decade, and EFT usage was determined individually depending on the physicians who specialized in MG among the 13 participating centers, this unmeasured confounder is advisable to be explored with a questionnaire about the factors that the physician mainly relies on to determine EFT usage. Otherwise, this unmeasured confounder can be obtained with instrumental variable analysis [2] or sensitivity analysis with an E-Value [3] to account for the unmeasured confounders.
Reference：
1.Uzawa A, Suzuki S, Kuwabara S, et al. Effectiveness of early cycles of fast-acting treatment in generalised myasthenia gravis. J Neurol Neurosurg Psychiatry. 2023 Jan 24; jnnp-2022-330519. doi: 10.1136/jnnp-2022-330519.
2.Maciejewski ML, Dowd BE, Norton EC. Instrumental Variables and Heterogeneous Treatment Effects. JAMA. 2022;327(12):1177-1178.
3.Haneuse S, VanderWeele TJ, Arterburn D. Using the E-Value to Assess the Potential Effect of Unmeasured Confounding in Observational Studies. JAMA. 2019;321(6):602-603.
Professor Sinclair and her team1 in Birmingham highlight an urgent issue affecting patients with IIH during the COVID19 pandemic. Their paper elegantly shows that weight gain worsens the severity of papilloedema and puts patients at risk of blindness. They also highlight the risk of worsening papilloedema not picked up with reduced access to hospital appointments.
Here, we report the audit results from our service and share practical actions that have been effective for our service, with wider applicability.
From May – Dec 2020, 58/102 (57%) IIH patients seen for follow up had gained weight compared to weight measured prior to pandemic by median 5.35 (range 0.6,27.3; SD 4.42)kg; with overall weight change of median 1.65 (range -24, 27.3; SD 6.81)kg for the group. 3/58 (5%) patients who gained weight, developed worsening papilloedema.
We agree with the importance of optic disc examination as highlighted by Sinclair and colleagues1, and the need for PPE precautions in the COVID19 pandemic setting. An option we found helpful is fundus photography of the optic disc in the community which the patient then emails their clinician. Fundus photography is now widely available at high-street optometrists. Benefits of doing this include: circumventing patients’ fears of attending hospitals during the pandemic; a patient-held record for future comparison; and the option for clinicians to obtain a colleague’s second opinion on the optic disc photograph.
Professor Sinclair and her team1 in Birmingham highlight an urgent issue affecting patients with IIH during the COVID19 pandemic. Their paper elegantly shows that weight gain worsens the severity of papilloedema and puts patients at risk of blindness. They also highlight the risk of worsening papilloedema not picked up with reduced access to hospital appointments.
Here, we report the audit results from our service and share practical actions that have been effective for our service, with wider applicability.
From May – Dec 2020, 58/102 (57%) IIH patients seen for follow up had gained weight compared to weight measured prior to pandemic by median 5.35 (range 0.6,27.3; SD 4.42)kg; with overall weight change of median 1.65 (range -24, 27.3; SD 6.81)kg for the group. 3/58 (5%) patients who gained weight, developed worsening papilloedema.
We agree with the importance of optic disc examination as highlighted by Sinclair and colleagues1, and the need for PPE precautions in the COVID19 pandemic setting. An option we found helpful is fundus photography of the optic disc in the community which the patient then emails their clinician. Fundus photography is now widely available at high-street optometrists. Benefits of doing this include: circumventing patients’ fears of attending hospitals during the pandemic; a patient-held record for future comparison; and the option for clinicians to obtain a colleague’s second opinion on the optic disc photograph.
In response to the pandemic, we set up technician-led IIH follow-up clinics for vision assessment, optic disc photography and optical coherence tomography (OCT). Patients were sent text message links to symptom questionnaires. Patients were then offered review in a group consultation (GC) setting by video. Those who opted out were offered one-to-one telephone review. The patient feedback for the GC have been overwhelming positive; details of this set up is further described elsewhere2.
A key part of our work with IIH patients is creating community and facilitating peer support, to tackle the sense of isolation from having the diagnosis, exacerbated by the COVID19 pandemic 3. In 2017 we started the IIH weight-loss and wellness (IIH-WoW) workshops on sustainable lifestyle measures for weight loss and wellbeing. Since May 2020 in response to the pandemic, these IIH-WoW workshops have been delivered via video calls. Topics covered included healthy habits and routines, nutrition, physical activity, emotional eating, stress management, goal setting and maintaining motivation. Feedback showed a median rating of 9/10 for ‘how much did you enjoy the workshop” and 8/10 for “how much benefit did you gain from the workshop”. The following patient responses to the question ‘What did you gain from the IIH-WoW workshop?’, illustrate the practical benefits gained from the sense of community, hope, and empowerment:
- “I think one of the challenges I've been experiencing has been - not just sharing my goals but being able to share it with someone who understands my motivation as we'd all ideally like to me free of IIH. That's not really something people in my friend circle can relate to and it's just really nice having that sense of community.”
- “Hearing others struggles. Being able to compare, share compassion, give and receive advice.”
- “Focus not just goals but actioning them and knowing others are doing the same and supporting each other.”
- “I gained two very significant things from this session. The first and most important is seeing and knowing that I'm not alone. I was diagnosed with IIH seven years ago and this event was the first opportunity I've had to meet others with the same condition. In the course of an hour, I went from being terribly isolated, to being part of a sisterhood of diverse, strong, and courageous women... I cannot overstate what a transformative experience that was. The second thing I gained is the sense of possibility. I've had numerous doctors tell me all the things I can't do... Dr Wong has shifted the focus back to what we can do, with small steps, targeted, realistic goals and with the wellbeing of our whole person in mind. In short, I've gained a new initiative.”
Patients valued the sense of peer support from these IIH-WoW and GC sessions, feeling less isolated particularly as IIH is a rare condition and they may feel stigmatised. We facilitate these group sessions using principles from Health Coaching 4 and Motivational Interviewing5, where patients are empowered to act and come up with their solutions.
In summary, we echo the concerns raised by Professor Sinclair and colleagues and highlight additional measures that could further support IIH patients during this pandemic.
Acknowledgements
This work was done at Guys & St Thomas’ (GSTT) NHSFT with the GSTT IIH Team. The IIH-WoW work was shortlisted in 2019 for the King’s Health Partners Education Academy Awards (Mind and Body category) and is only possible with the support from the GSTT IIH Team; the Eye Dept; Deborah Gibson; Dr Denise Ratcliffe; dietetics and physiotherapy teams. The Group Consultation work was awarded top abstract for the British Society of Lifestyle Medicine 2020 conference and shortlisted for the HSJ Acute Sector Innovation Award (2021); supported by Group Consultations Ltd.
Conflicts of interest
None to declare
Funders
None
References
1. Thaller M, Tsermoulas G, Sun R, Mollan SP, Sinclair AJ. Negative impact of COVID-19 lockdown on papilloedema and idiopathic intracranial hypertension. J Neurol Neurosurg Psychiatry. 2020 Dec 24:jnnp-2020-325519. doi: 10.1136/jnnp-2020-325519. Epub ahead of print. PMID: 33361411.
2. Wong SH, Barrow N, Hall K, Gandesha P, Manson A. The Effective Management of Idiopathic Intracranial Hypertension Delivered by In-person and Virtual Group Consultations: Results and Reflections from a Phase One Service Delivery. Neuroophthalmology. 2021 May 10;45(4):246-252. doi: 10.1080/01658107.2021.1887287. PMID: 34366512; PMCID: PMC8312588.
3. Miller ED. Loneliness in the Era of COVID-19. Front Psychol. 2020 Sep 18;11:2219. doi: 10.3389/fpsyg.2020.02219. PMID: 33071848; PMCID: PMC7530332.
4. Conn S, Curtain S. Health coaching as a lifestyle medicine process in primary care. Aust J Gen Pract. 2019 Oct;48(10):677-680. doi: 10.31128/AJGP-07-19-4984. PMID: 31569315.
5. Rollnick, S., & Miller, W. What is Motivational Interviewing? Behavioural and Cognitive Psychotherapy 1995, 23(4), 325-334. doi:10.1017/S135246580001643X
I recently read the article titled "Somatic symptom disorder in patients with post-COVID-19 neurological symptoms: a preliminary report from the somatic study (Somatic Symptom Disorder Triggered by COVID-19)" published in the Journal of Neurology, Neurosurgery, and Psychiatry. As a psychiatrist in Taiwan, I found the findings of the study intriguing and relevant to the mental health challenges faced by our population during the COVID-19 pandemic.
In Taiwan, we have observed similar situations where the pandemic has had a significant impact on mental health. Our recent study, "Mental health impact of the COVID-19 pandemic in Taiwan,"1 published in the Journal of Formosan Medical Association, explored the prevalence of psychiatric distress, suicidal ideation, and levels of worry during the pandemic among a representative sample of 1,087 Taiwanese. The results showed that approximately 12% of respondents experienced psychiatric distress, and about 10% expressed concerns over financial troubles, employment, and mental health conditions.
While the prevalence of psychiatric distress in Taiwan is lower compared to other countries, the study highlights the undeniable effect the pandemic has had on mental health. It is important to acknowledge that the COVID-19 crisis goes beyond health and mental health issues, as its socio-economic impact could have long-lasting consequences if not adequately addressed.
I recently read the article titled "Somatic symptom disorder in patients with post-COVID-19 neurological symptoms: a preliminary report from the somatic study (Somatic Symptom Disorder Triggered by COVID-19)" published in the Journal of Neurology, Neurosurgery, and Psychiatry. As a psychiatrist in Taiwan, I found the findings of the study intriguing and relevant to the mental health challenges faced by our population during the COVID-19 pandemic.
In Taiwan, we have observed similar situations where the pandemic has had a significant impact on mental health. Our recent study, "Mental health impact of the COVID-19 pandemic in Taiwan,"1 published in the Journal of Formosan Medical Association, explored the prevalence of psychiatric distress, suicidal ideation, and levels of worry during the pandemic among a representative sample of 1,087 Taiwanese. The results showed that approximately 12% of respondents experienced psychiatric distress, and about 10% expressed concerns over financial troubles, employment, and mental health conditions.
While the prevalence of psychiatric distress in Taiwan is lower compared to other countries, the study highlights the undeniable effect the pandemic has had on mental health. It is important to acknowledge that the COVID-19 crisis goes beyond health and mental health issues, as its socio-economic impact could have long-lasting consequences if not adequately addressed.
In light of the findings of the somatic study and our own research, I believe it is essential for healthcare professionals worldwide to collaborate and share knowledge to better understand and manage the mental health consequences of COVID-19. Expanding efforts to improve economic security and achieve a rapid governmental socio-economic response are crucial to mitigate the future impact of the pandemic on mental health.
I would like to express my appreciation for your publication of the somatic study, which contributes valuable insights to the understanding of the mental health challenges associated with COVID-19. I hope that our collective efforts will lead to better mental health care for our patients during these trying times.
Sincerely,
Dr. Lien-Chung Wei
Psychiatrist
Taiwan
1. Chen YY, Wu KC, Gau SS. Mental health impact of the COVID-19 pandemic in Taiwan. Journal of the Formosan Medical Association = Taiwan yi zhi 2021;120(7):1421-23. doi: 10.1016/j.jfma.2020.12.002 [published Online First: 2020/12/29]
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...
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 percentage variation between 5.8% and 13.6% across healthcare regions (2) which indicates that botulinum toxin is among key treatments for spasticity in Swedish population and it would be better if the authors could add the information regarding its use to the work. Second, as the authors aimed to assess the treatment pattern and associated factors with medication use, different factors which were identified previously to be in association with medication use pattern should had been considered in this study and been taken care of in the regression modelling analysis. Besides, as treatment cessation was assessed in this study, consideration of factors that are highly associated with adherence to treatment such as socioeconomic factors would have increased the validity of the findings of the study (3, 4). Furthermore, there seems to be a mismatch between prevalent spasticity and prevalent MS diagnosis. In this study, prevalent MS diagnosis defined when a patient was diagnosed with MS before the start time of the study, 1st of July, 2005; prevalent spasticity was defined as receiving spasticity treatments within the first year of evaluation time from 1 July 2005 to 1 July 2006 and patients with prevalent spasticity were then excluded from the study. This, however, could result in bias when depicting the treatment pattern of patients with prevalent diagnosis of MS. The authors also excluded patients with possible spasticity treatments before MS diagnosis were excluded. Previous studies have shown that there might be weeks, months to years of delay from initial symptoms/signs of MS to the clinical diagnosis by a physician (5-7). The patients with MS could have clinical manifestations long before they’ve been diagnosed with MS and therefore, they probably have sought the medical treatment before the diagnosis; spasticity is among these manifestations (8). Therefore, as the authors assumed that MS is likely the cause that patients without any other registered diseases that could result in spasticity were using spasticity treatment, I believe that it would be better not to exclude “all” the patients with spasticity treatment before MS diagnosis; they could just exclude patients with baclofen use for a long time, for example one year, before the diagnosis of MS and those who were known to have other diseases as a cause for spasticity.
Acknowledgement: None.
Conflict of Interest statement: I declare no conflict of interests.
Funding: None.
References
1. Smith KA, Piehl F, Olsson T, Alfredsson L, Hillert J, Kockum I, et al. Spasticity treatment patterns among people with multiple sclerosis: a Swedish cohort study. Journal of neurology, neurosurgery, and psychiatry. 2022.
2. Forsmark A, Rosengren L, Ertzgaard P. Inequalities in pharmacologic treatment of spasticity in Sweden – health economic consequences of closing the treatment gap. Health Economics Review. 2020;10(1):4.
3. Flemmen HØ, Simonsen CS, Broch L, Brunborg C, Berg-Hansen P, Moen SM, et al. The influence of socioeconomic factors on access to disease modifying treatment in a Norwegian multiple sclerosis cohort. Multiple Sclerosis and Related Disorders. 2022;61:103759.
4. Kołtuniuk A, Chojdak-Łukasiewicz J. Adherence to Therapy in Patients with Multiple Sclerosis—Review. 2022;19(4):2203.
5. Patti F, Chisari CG, Arena S, Toscano S, Finocchiaro C, Fermo SL, et al. Factors driving delayed time to multiple sclerosis diagnosis: Results from a population-based study. Multiple Sclerosis and Related Disorders. 2022;57:103361.
6. Adamec I, Barun B, Gabelić T, Zadro I, Habek M. Delay in the diagnosis of multiple sclerosis in Croatia. Clinical Neurology and Neurosurgery. 2013;115:S70-S2.
7. Kingwell E, Leung AL, Roger E, Duquette P, Rieckmann P, Tremlett H. Factors associated with delay to medical recognition in two Canadian multiple sclerosis cohorts. Journal of the Neurological Sciences. 2010;292(1):57-62.
8. Ford H. Clinical presentation and diagnosis of multiple sclerosis. Clinical medicine (London, England). 2020;20(4):380-3.
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...
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 between symptoms onset to the diagnosis and the time between the diagnosis to the treatment initiation with disease modifying agents for to have a more holistic picture.
Second, the study aimed to compare the patient-reported outcomes between two groups of the patients with multiple sclerosis, those with early treatment and those with late treatment; however, they did not consider the issue that different factors were already identified in the literature to be associated with symptoms and outcomes reported by patients and these factors should also be should be added into the statistical analyses when measuring the association of the timing of treatment and the outcomes. In a study conducted by Farran et al. on patients with multiple sclerosis in Lebanon and the Middle East and North Africa region, it was shown that age of these individuals, their gender and some sociodemographic and clinical variables could be associated with their perceived symptom and health-related quality of life (5). In this study it was mentioned in Table 1 that there were significant differences in the age and gender of the two groups of the study which could endanger the credibility of the findings in the study. Besides, the participants of these two groups had even significantly different baseline number of relapses and pretreatment Expanded Disability Status Scale; therefore, the disease status and severity might be different in these two groups, a potential source for another bias.
Authors’ contributions: Both authors contributed in all processes of the preparation of this paper.
Acknowledgement: None.
Conflict of Interest statement: I declare no conflict of interests.
Funding: None.
References
1. He A, Spelman T, Manouchehrinia A, Ciccarelli O, Hillert J, McKay K. Association between early treatment of multiple sclerosis and patient-reported outcomes: a nationwide observational cohort study. Journal of Neurology, Neurosurgery &amp; Psychiatry. 2022:jnnp-2022-330169.
2. Karampampa K, Gyllensten H, Murley C, Alexanderson K, Kavaliunas A, Olsson T, et al. Early vs. late treatment initiation in multiple sclerosis and its impact on cost of illness: A register-based prospective cohort study in Sweden. Multiple sclerosis journal - experimental, translational and clinical. 2022;8(2):20552173221092411.
3. Kavaliunas A, Manouchehrinia A, Stawiarz L, Ramanujam R, Agholme J, Hedström AK, et al. Importance of early treatment initiation in the clinical course of multiple sclerosis. Multiple sclerosis (Houndmills, Basingstoke, England). 2017;23(9):1233-40.
4. Landfeldt E, Castelo-Branco A, Svedbom A, Löfroth E, Kavaliunas A, Hillert J. The long-term impact of early treatment of multiple sclerosis on the risk of disability pension. Journal of neurology. 2018;265(3):701-7.
5. Farran N, Safieddine BR, Bayram M, Abi Hanna T, Massouh J, AlKhawaja M, et al. Factors affecting MS patients’ health-related quality of life and measurement challenges in Lebanon and the MENA region. 2020;6(1):2055217319848467.
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...
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 general population comparison group. To accommodate this, one general population observation was re-allocated from no event to event" and then say that the absolute number was "low" without explaining exactly what this means. We think it is likely that 5 events in the rugby group would be consistent with an odds ratio of 15, i.e. (5/407)/(1/1235)=15.17. Although this does appear to indicate an apparent increase in risk, we question the validity of trying to quantify the risk when this can only be achieved by modifying the data, and with such modification the conclusion has very little certainty. It is unfortunate that this may have led to misunderstanding in several media reports.
We reiterate this work is important and points towards an increase in risk for many of the outcomes reported, but the risks in public health terms for relatively rare outcomes should not be exaggerated until they can be replicated in larger samples.
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...
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.g., teeth-cleaning, toileting, drinking, mobility, transfers, etc), so the lack of effect on the primary outcome measure is not surprising and might have been anticipated. Yet despite these limitations it seems this intervention, like others, did promote personal goal attainment.
Personal goal attainment is valued by people with dementia and carers who find cognitive rehabilitation helpful and say that it enhances confidence and well-being and assists in adjusting to the diagnosis. It might also have longer-term benefits. The ETNA-3 trial[6] tested a personalised cognitive rehabilitation intervention provided by qualified health professionals comprising weekly individual sessions for 3 months followed by six-weekly maintenance sessions with telephone support for the carer over a 21-month period. This resulted in significantly lower functional disability and a six-month delay in institutionalisation at the two-year follow up relative to group cognitive training, group reminiscence therapy and usual care.
Some inaccuracies require comment. First, contrary to what is suggested in the discussion of this paper, the precursor trial to GREAT[4] adopted a rigorous design consistent with criteria for high-quality evidence.[7] Participants had eight home visits from an experienced occupational therapist, and where indicated were supported to learn to use relevant aids and adaptations. Second, it is not the case that other studies have recruited fewer participants and offered fewer sessions. ETNA-3[6] randomised 653 people with dementia in 40 trial sites and provided an extensive intervention schedule. GREAT[2] randomised 475 people with dementia in eight trial sites and offered ten sessions with up to four maintenance sessions.
In conclusion, it is time to stop setting unrealistic expectations about what outcomes interventions should achieve. Instead, we should focus on what is most meaningful for people with dementia and their families and build on what we know can be done. We know that we can enable people with dementia to improve their functioning in relation to chosen activities that are important and meaningful for them using evidence-based cognitive rehabilitation strategies, which include but are not limited to the use of aids and adaptations. A recent implementation study8 has shown that the GREAT intervention is equally effective when offered within normal services and can be provided at modest cost. Supporting functional ability in areas that are personally meaningful may have worthwhile long-term benefits for people with dementia and their families.
References
1. Chester H, Beresford R, Clarkson P, et al. The Dementia Early Stage Cognitive Aids New Trial (DESCANT) intervention: A goal attainment scaling approach to promote self-management. International Journal of Geriatric Psychiatry 2021;36(5):784-93. doi: 10.1002/gps.5479
2. Clare L, Kudlicka A, Oyebode JR, et al. Individual goal-oriented cognitive rehabilitation to improve everyday functioning for people with early-stage dementia: a multi-centre randomised controlled trial (the GREAT trial). International Journal of Geriatric Psychiatry 2019;34:709-12. doi: 10.1002/gps.5076
3. Voigt-Radloff S, de Werd MME, Leonhart R, et al. Structured relearning of activities of daily living in dementia: the randomised controlled REDALI-DEM trial on errorless learning. Alzheimer's Research and Therapy 2017;9:22. doi: 10.1186/s13195-017-0247-9
4. Clare L, Linden DE, Woods RT, et al. Goal-oriented cognitive rehabilitation for people with early-stage Alzheimer’s disease: a single-blind randomized controlled trial of clinical efficacy. American Journal of Geriatric Psychiatry 2010;18:928-39. doi: 10.1097/JGP.0b013e3181d5792a
5. Hindle JV, Watermeyer TJ, Roberts J, et al. Goal-oriented cognitive rehabilitation for dementias associated with Parkinson’s disease. International Journal of Geriatric Psychiatry 2018;33:718-28. doi: 10.1002/gps.4845
6. Amieva H, Robert PH, Grandoulier AS, et al. Group and individual cognitive therapies in Alzheimer’s disease: the ETNA3 randomized trial. International Psychogeriatrics 2016;28:707-17. doi: 10.1017/S1041610215001830
7. Bahar-Fuchs A, Clare L, Woods RT. Cognitive training and cognitive rehabilitation for mild to moderate Alzheimer's disease and vascular dementia. Cochrane Database of Systematic Reviews 2013(6) doi: 10.1002/14651858.CD003260.pub2
8. Clare L, Kudlicka A, Collins RA, et al. Implementing a home-based personalised cognitive rehabilitation intervention for people with mild-to-moderate dementia: GREAT into Practice. 2022 (preprint) doi: 10.21203/rs.3.rs-1458590/v1
We are writing to respectfully offer some additional comments on the recent publication of Hannaway et al. in JNNP titled “Visual dysfunction is a better predictor than retinal thickness for dementia in Parkinson’s disease”.
While the authors provided interesting insights on the predictive value of higher order visual functions for dementia, we noticed that the authors did not find significant associations between parafoveal GCIPL (pfGCIPL) and cognition in their work, whereas our research did. As they mentioned, the range of cognitive impairment was higher in our sample, and possibly this might have driven our findings. However, we would like to add that the relationship between the retina and cognition is not linear, according to our data. As such, we calculated relative risks by categorizing continuous variables, which allowed us to identify non-linear relationships between pfGCIPL and cognitive impairment. Furthermore, we speculate that these variables do not exhibit a synchronous pattern of change over time, suggesting that the temporal trends are not closely linked, which might justify the lack of association in the current work.
We do agree with the authors in that visual function is a good predictor of cognitive deterioration. Our previous work also demonstrated this fact, but we would like to highlight the benefits of retinal OCT imaging in this context, if its utility is validated. Retinal OCT imaging is a faster and easier-to-measure technique com...
Show MoreAyton et al. reported the association between ferritin, apolipoprotein E (APOE) and dementia-related biomarkers such as amyloid β42/total-tau and phosphorylated tau181 (p-tau181) in cerebrospinal fluid (CSF) (1). CSF ferritin and APOE were positively associated with p-tau181, which was most predominant in subjects without increase in amyloid β42/total-tau. I present information about the study.
Pan et al. investigated the associations of CSF ferritin and CSF biomarkers of Alzheimer's disease (AD) (2). They found that CSF ferritin increased in subjects with more advanced categories of CSF biomarkers such as amyloid β42 and p-pau, although there were stronger relationships of CSF ferritin with p-tau and t-tau, rather than amyloid β42. This means that biological action of ferritin in the brain for AD may be more closely related to tau protein.
Baringer et al. described brain iron homeostasis in Alzheimer's disease, Parkinson's disease, and other neurodegenerative diseases (3). They emphasized that endothelial cells of the blood-brain barrier were the site of iron transport regulation, and iron uptake, transcytosis, and release were mainly conducted. By controlling the excess of brain iron, neurodegenerative disorders may be improved. The mechanism that tau protein spreads through functionally connected neurons in Alzheimer's disease have been precisely reported (4), and it may be related to the excess of brain iron storage.
References...
Show MoreÅkerstedt et al. conducted a case-control study with 2075 cases and 3164 controls to investigate the association between sleep and risk of multiple sclerosis (MS) (1). Sleep duration, circadian disruption and sleep quality during adolescence were used for sleep variables. The authors calculated the adjusted OR with 95% CIs using logistic regression models, and short sleep (<7 hours/night) and low sleep quality were significantly associated with increased risk of developing MS. I have a question regarding the ways of multivariate analysis.
The ratio in the number of cases and controls is about 1.5 in this study. If the authors selected unconditional logistic regression analysis, OR might become conservative. If the authors selected conditional logistic regression analysis, the increased number of controls is preferable to make stable estimation. Instead of selecting a case-control study with a matching procedure, using all pooled data without a matching procedure can be selected for the analysis (2).
Anyway, a recall method has a possibility of including bias and risk assessment of MS with subjective sleep variables should be paid with caution.
References
Show More1. Åkerstedt T, Olsson T, Alfredsson L, et al. Insufficient sleep during adolescence and risk of multiple sclerosis: results from a Swedish case-control study. J Neurol Neurosurg Psychiatry 2023;94(5):331-6.
2. Hamajima N, Hirose K, Inoue M, et al. Case-control studies: matched controls...
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.
Show More1. 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...
Professor Sinclair and her team1 in Birmingham highlight an urgent issue affecting patients with IIH during the COVID19 pandemic. Their paper elegantly shows that weight gain worsens the severity of papilloedema and puts patients at risk of blindness. They also highlight the risk of worsening papilloedema not picked up with reduced access to hospital appointments.
Here, we report the audit results from our service and share practical actions that have been effective for our service, with wider applicability.
From May – Dec 2020, 58/102 (57%) IIH patients seen for follow up had gained weight compared to weight measured prior to pandemic by median 5.35 (range 0.6,27.3; SD 4.42)kg; with overall weight change of median 1.65 (range -24, 27.3; SD 6.81)kg for the group. 3/58 (5%) patients who gained weight, developed worsening papilloedema.
We agree with the importance of optic disc examination as highlighted by Sinclair and colleagues1, and the need for PPE precautions in the COVID19 pandemic setting. An option we found helpful is fundus photography of the optic disc in the community which the patient then emails their clinician. Fundus photography is now widely available at high-street optometrists. Benefits of doing this include: circumventing patients’ fears of attending hospitals during the pandemic; a patient-held record for future comparison; and the option for clinicians to obtain a colleague’s second opinion on the optic disc photograph.
I...
Show MoreDear Editor,
I recently read the article titled "Somatic symptom disorder in patients with post-COVID-19 neurological symptoms: a preliminary report from the somatic study (Somatic Symptom Disorder Triggered by COVID-19)" published in the Journal of Neurology, Neurosurgery, and Psychiatry. As a psychiatrist in Taiwan, I found the findings of the study intriguing and relevant to the mental health challenges faced by our population during the COVID-19 pandemic.
In Taiwan, we have observed similar situations where the pandemic has had a significant impact on mental health. Our recent study, "Mental health impact of the COVID-19 pandemic in Taiwan,"1 published in the Journal of Formosan Medical Association, explored the prevalence of psychiatric distress, suicidal ideation, and levels of worry during the pandemic among a representative sample of 1,087 Taiwanese. The results showed that approximately 12% of respondents experienced psychiatric distress, and about 10% expressed concerns over financial troubles, employment, and mental health conditions.
While the prevalence of psychiatric distress in Taiwan is lower compared to other countries, the study highlights the undeniable effect the pandemic has had on mental health. It is important to acknowledge that the COVID-19 crisis goes beyond health and mental health issues, as its socio-economic impact could have long-lasting consequences if not adequately addressed.
In light of the...
Show MoreDr 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.
Show MoreFirst, 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...
To the Editor
Show MoreI 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...
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...
Show MoreThe 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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