eLetters

47 e-Letters

published between 2017 and 2020

  • Mechanism for ischaemic stroke in COVID-19 - full evaluation needed

    Dear Editor

    It is with great interest that I read the excellent paper by Beyrouti R, et al, on the characteristics of ischaemic stroke among patients with COVID-19(1). There is great interest in the prothromotic state seen in this illness – in this series, high D-dimer and fibrinogen levels in 6/6, positive lupus anticoagulant in 4/5, moderate anti-cardiolipin titres in 1/6.

    But I note that there are still some traditional mechanisms in these patients that may have been the cause of the stroke that may not have been fully elucidated, or if they were, were not reported in the paper. I see that patients 2 and 3 had atrial fibrillation, on warfarin, with supra-therapeutic (3.6, artificial heart valve) and sub-therapeutic (1.03) INRs respectively. The results of echocardiography and cardiac rhythm monitoring were not reported for any patient. Thus cardioembolism is still possible as a cause of stroke. Patients 2 to 5 had hypertension and at least one other atherosclerotic vascular risk factor (eg diabetes mellitus, hypercholesterolaemia, smoking, stroke). All patients save 1 was above 60 years of age. Vascular imaging was only reported for 2 cases (5 - CTA and 6 - MRA). Atherothromboelbolism may have caused stroke in some of the patients.

    I refer to case series of stroke seen during the 2002-2204 SARS epidemic, also due to a corona virus (2); all had large artery ischaemic strokes, at least 2 of 4 assessed patients had a cardioembolic source, with anot...

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  • Corona viruses and Stroke

    Dear Editor,

    The editorial by Manji et al.1 on the neurology of the COVID-19 pandemic cites Mao et al2.’s report describing 5 ischemic strokes in 214 COVID-19 patients. Helms et al3,. and Zhang et al4. have also since reported ischemic stroke in patients with severe SARS-CoV-2 infection, with the latter linking stroke to antiphospholipid antibodies4. In addition, Oxley et al. describe large-vessel stroke in 5 young patients5. In this context, I would like to highlight our 2003 study of ischemic stroke in severe SARS-CoV-1 infection, the corona virus responsible for Severe Acute Respiratory Syndrome (SARS)6. Five out of a total of 206 SARS patients in the country developed large artery ischemic stroke7, four of whom were critically ill. They were not significantly older (56±13 years) than other critically-ill SARS patients (50±16 years, Anova p=0.45). Besides episodes of hypotension, we suspected thromboembolism as a possible mechanism of stroke. Four of the eight SARS patients, who had autopsy examination, revealed evidence of pulmonary thromboemboli8. One was a 39-year-old man, with no stroke risk factors, who died two weeks after contracting SARS; his autopsy revealed unilateral occipital lobe infarction, sterile vegetations on multiple valves, deep venous thrombosis and pulmonary embolism. This prompted the subsequent use of low molecular weight heparin (LMWH) in critically-ill patients, at doses to achieve anti-Xa levels of 0.5-1.0IU/ml. Nevertheless, one-thir...

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  • Study rigor may not impact finding of neuroablation superiority over deep brain stimulation for obsessive-compulsive disorder

    Introduction:

    Obsessive-compulsive disorder (OCD) is a neuropsychiatric disease characterized by distressing thoughts or urges that often require repetitive behaviors to suppress. OCD affects 2-3% of the general population and can have debilitating effects on normal functioning.[1] While most cases of OCD can be addressed through psychotherapy and/or medication, about 10% remain refractory, requiring neurosurgical intervention, such as neuroablation (ABL) or deep brain stimulation (DBS). These options possess their own respective advantages and disadvantages. ABL lacks the hardware concerns of DBS (e.g. device failure, battery replacement, etc.) and may be incisionless (e.g. stereotactic radiosurgery). Alternatively, DBS is non-lesional, and stimulation parameters can be titrated. While both ABL and DBS appear to be effective for refractory OCD, there is no clear consensus on their relative superiority/non-inferiority.

    Our group previously sought to address this question by comparing the two treatments’ relative utility. [1] Using a random-effects, inverse-variance weighted meta-analysis of 56 studies, utility was calculated from Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores and adverse event (AE) incidence. In our analysis, no significant differences were found between stereotactic radiosurgery and radiofrequency ablation, so their studies were combined and all considered under ABL. Ultimately, ABL yielded a significantly greater utility compared to...

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  • RE: Neurofilament light chain and C reactive protein explored as predictors of survival in amyotrophic lateral sclerosis

    De Schaepdryver et al. assessed the prognostic ability of serum neurofilament light chain (NfL) and C-reactive protein (CRP) in patients with amyotrophic lateral sclerosis (ALS) (1). Although two indicators can significantly predict the prognosis, the superiority by the combination of NfL and CRP should be checked for the analysis. I want to discuss NfL and ALS prognosis from recent publications.

    Verde et al. conducted a prospective study to determine the diagnostic and prognostic performance of serum NfL in patients with ALS (2). Serum NfL positively correlated with disease progression rate in patients with ALS, and higher levels were significantly associated with shorter survival. In addition, serum NfL did not differ among patients in different ALS pathological stages, and NfL levels were stable over time within each patient.

    Regarding the first query, Thouvenot et al. reported that serum NfL could be used as a prognostic marker for ALS at the time of diagnosis (3). Gille et al. recognized the relationship of serum NfL with motor neuron degeneration in patients with ALS (4). They described that serum NfL was significantly associated with disease progression rate and survival, and it could be recommended as a surrogate biomarker of ALS. These two papers presented no information whether NfL can be used for monitoring of ALS progression in each patient.

    De Schaepdryver et al. used two indicators, and I suspect that the authors can present information r...

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  • RE: Neurofilament light chain in serum for the diagnosis of amyotrophic lateral sclerosis

    Verde et al. conducted a prospective study to determine the diagnostic and prognostic performance of serum neurofilament light chain (NFL) in patients with amyotrophic lateral sclerosis (ALS) (1). Serum NFL positively correlated with disease progression rate in patients with ALS, and higher levels were significantly associated with shorter survival. In addition, serum NFL did not differ among patients in different ALS pathological stages, and NFL levels were stable over time within each patient. I have a concern about their study.

    Gille et al. also recognized the relationship of serum NFL with motor neuron degeneration in patients with ALS (2). They also recognized that serum NFL was significantly associated with disease progression rate and survival. Serum NFL can be recommended as a surrogate biomarker of ALS.

    Regarding the first concern, Thouvenot et al. also checked if serum NFL can be used as a prognostic marker for ALS at the time of diagnosis (3). By Cox regression analysis, NFL, weight loss and site at onset were independent predictive factors of mortality, and higher NFL concentration at the time of diagnosis is the strongest prognostic fact

    I recently discussed on serum neurofilament light chain in patients with amyotrophic lateral sclerosis (4), and these consistent results should also be verified by a meta-analysis of prospective studies.

    References

    1. Verde F, Steinacker P, Weishaupt JH, et al. Neurofilament light chain in se...

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  • Autonomic symptoms as a predictor of disease progression and survival in patients with progressive supranuclear palsy

    Oliveira et al. evaluated the association between autonomic symptoms and progressive supranuclear palsy (PSP) with special reference to disease progression and survival (1). Adjusted hazard ratios (HRs) (95% confidence interval [CIs]) of early constipation and early urinary symptoms for the risk of first disease milestone of PSP were 0.88 (0.83 to 0.92) and 0.80 (0.75 to 0.86), respectively. In addition, adjusted HRs (95% CIs) of early constipation and early urinary symptoms for survival were 0.73 (0.64 to 0.84) and 0.88 (0.80 to 0.96), respectively. Furthermore, Richardson syndrome phenotype was significantly associated with shorter survival. The authors concluded that earlier urinary symptoms and constipation are closely associated with rapid disease progression and shorter survival in patients with PSP. I have two comments about their study.

    First, Glasmacher et al. conducted a meta-analysis to explore prognostic factors and survival in patients with PSP and multiple system atrophy (MSA) (2). In patients with PSP, adjusted HR (95% CI) of Richardson's phenotype against Parkinson's phenotype for shorter survival was 2.37 (1.21 to 4.64). In addition, adjusted HR (95% CI) of early fall for shorter survival in patients with PSP and MSA was 2.32 (1.94 to 2.77). Although some clinical symptoms are overlapping by common neurological damages, risk assessment for PSP and for MSA should be separately conducted. Stable estimates with enough number of samples and ev...

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  • Ultra-high-dose methylcobalamin in amyotrophic lateral sclerosis

    Kaji et al. evaluated the efficacy and safety of intramuscular ultra-high-dose methylcobalamin in 373 patients with amyotrophic lateral sclerosis (ALS) (1). The primary endpoints were death or full ventilation support. Although there was no significant difference between treated and control group, 50 mg methylcobalamin-treated patients with early start within 12 months' duration of diagnosis showed longer time intervals to the primary event and keep the Revised ALS Functional Rating Scale (ALSFRS-R) score than the placebo group. The adverse effects by this treatment were similar and low prevalence among placebo, 25 mg or 50 mg groups. The authors recommend to verify the prognosis by this medication, and I have some concerns about their study.

    First, the authors did not allow the change of riluzole administration and did not handle patients with edaravone treatment. I think that the vitamin B12 analog treatment in combination with recent neuro-protective drugs might be acceptable for future trials (2). In addition, the efficacy for ALS by methylcobalamin should be specified by adjusting several confounders for the analysis.

    Relating to vitamin therapy for ALS, Rosenbohm et al. investigated the association of serum retinol-binding protein 4 (RBP4) with the onset and prognosis of ALS (3). Adjusted ORs (95% C) of the highest quartile of RBP4 against lowest quartile for incident ALS was 0.36 (0.22-0.59). In addition, serum RBP4 was inversely associated with m...

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  • Reducing Uncertainty and Expanding Patient Engagement in Deep Brain Stimulation Trials for Tourette Syndrome

    We appreciate the editorial by Dr. Muller-Vahl [1] about our recent article [2]. The large, international study group who co-authored our paper collectively felt that it would be useful to provide clarification of a few important points regarding the International Tourette Syndrome (TS) Deep Brain Stimulation (DBS) Database and Registry, the International Neuromodulation Registry, and our published analysis.

    There is widespread agreement on the need for more randomized controlled trials (RCTs) to evaluate the efficacy of DBS for many indications, including TS, and there has been substantial discussion in the medical community about how these trials should be organized and carried out [3]. Our approach to overcome the challenges with the modest amount of data available for surgical therapies for TS has been to use symbiotic data sharing [4]. This approach encourages the broadening of investigative teams after publication of clinical studies to perform additional analyses and to develop new hypotheses. The key concept behind this approach is that new investigators work in a close, collaborative relationship with the teams that conducted the initial data collection. In addition, a recent viewpoint from the Food & Drug Administration in the United States reported that “For some devices, opportunities exist for leveraging alternative data sources, such as existing registries or modeling techniques, to allow regulators to have a good idea of the risks and benefits of...

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  • The utility of CSF biomarkers in idiopathic normal pressure hydrocephalus?

    Dear Editor,
    The original article by Jeppsson et al. provides substantial perspectives regarding the diagnostic
    significance of cerebrospinal fluid (CSF) biomarkers in discriminating patients with idiopathic normal pressure hydrocephalus (iNPH) from patients with other neurodegenerative disorders. 1 They have found that patients with iNPH had, compared with healthy individuals, lower concentrations of P-tau and APP-derived proteins in combination with elevated MCP-1 1. Moreover, compared with the non-iNPH disorders group, iNPH was characterized by the same significant change; low concentration of tau proteins and APP-derived proteins, and elevated MCP-1. I sincerely appreciate the authors for conducting such a large-scale study of a strictly interesting topic. However, I would like to make some comments hoping to provide a better understanding of some points and some perspectives to be kept in mind while planning future related studies
    In my opinion, the investigation of CSF biomarkers in patients with iNPH may provide several insights in addition to discriminating the iNPH patients from other neurodegenerative diseases. Certainly, these study results may give the opportunity to understand the unknown pathophysiological aspects of iNPH, thereby, even leading to new classifications of the disease. Actually, there may be many questions to be clarified regarding diagnostic approach, evaluation of the iNPH patients and even identification of the disease. 2,3...

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  • Split weakness signs in ALS
     I note the clinical analysis of differential weakness in ALS in elbow flexion (biceps brachii) compared to elbow extension (triceps) reported by Khalaf et al.1 This is described as analogous to similar 'split' muscle weakness around the ankle joint and, particularly, as that found in flexor digitorum indicis (FDI) compared to abductor digit minim (ADM) in the hand in the disease. It should be remembered that, although characteristic of ALS, this differential pattern of weakness has repeatedly been found not to be unique to ALS, even from the first descriptions.2,3 As the authors, and Vucic in his editorial remark,1,4 the cause of this interesting pattern of weakness in ALS remains uncertain. The finding of an association between the pattern of weakness and increased excitability in the upper motor neuron system in ALS does not necessarily provide primary support for an upper motor neuron (UMN) causation.  Nonetheless this pattern of weakness must be important in the disease. It is worth remembering that differential susceptibility to neurogenic lower motor neuron weakness is also a characteristic feature of some peripheral neuropathies, e.g., the Charcot-Marie-Tooth syndromes. Furthermore, differential muscle weakness and atrophy is a characteristic finding that is important in clinical diagnosis in the myriad different genetically determined muscular dystrophies.5 Although the causation of this differential susceptibility of certain muscles in this la...
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