eLetters

564 e-Letters

  • EARLY DIAGNOSIS OF PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY: A STILL UNRESOLVED CLINICAL CHALLENGE

    Dear Editor,
    We have read with great interest the work by Scarpazza et al that provided a longitudinal MRI evaluation of natalizumab-related Progressive Multifocal Leukoencephalopathy (NTZ-PML) lesions in Multiple Sclerosis (MS) patients (1).
    Their central finding was the high percentage (78.1%) of patients, who eventually developed NTZ-PML, in whom highly suggestive lesions were already retrospectively detectable on pre-diagnostic MRI exams. Furthermore, the pre-diagnostic phase proved to be relatively long (150.8±74.9 days), with an estimated percentage increase of the lesions’ volume of 62.8% per month (1).
    Given the widely recognized crucial role of a timely NTZ-PML identification in reducing mortality and residual disability (1), these results present the neurological and neuroradiological communities with an important clinical challenge, prompting a major effort to ensure an early diagnosis of this condition.
    Although redefining the timing of MRI surveillance, with up to one brain MRI exam every 3-4 months for high-risk patients, appears as a justified strategy, we think that improving the accuracy of early identification of NTZ-PML is also mandatory.
    In our opinion, such achievement should be pursued using two complementary approaches: (i) a specific training addressed to neuroradiologists working in the field of MS, who should be aware of the relevance of even very small asymptomatic PML lesions and how to differentiate them from new M...

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  • Author reply: Higher burden of common neurological diseases in women than in men

    Dear Editor,

    We thank Abat et al. for re-emphasizing an important interpretation of our work, namely that sex-differences in life-expectancy likely influenced the presented lifetime risks [1]. Indeed, in our paper we repeatedly discussed in several sections (for instance in the methods) that differences in life-expectancy between men and women could differentially affect their lifetime risk. It was for this reason that we consequently decided to analyze the data in a sex-specific manner while taking the competing risk of death into account in order to prevent potential overestimation.

    Abat et al. unfortunately also allege that we attributed the observed sex-differences in disease risk to sex-specific effects on a biological level. The authors have seemingly missed our discussion at length arguing that observed differences in lifetime risk may be primarily attributed to the effects of differences in life-expectancy between men and women: “Apart from a longer life-expectancy in general, these findings may be explained by smaller differences in life-expectancy between men and women in the Netherlands (1.8 years), compared with the USA (4.8 years). With longer life-expectancy, individuals in this study simply had more time to develop these diseases in a timeframe with high age-specific incidence rates.”

    It seems thus that ours and Abat and co-authors’ interpretation of our findings is pretty much congruent, i.e. age, irrespective of sex, should be consid...

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  • Higher burden of common neurological diseases in women than in men: it is because women live longer!

    To the Editor,
    We read with interest the work from Licher et al. [1] in which the authors tried to quantify the burden of common neurological diseases (i.e. dementia, stroke and parkinsonism) in 12 102 individuals (6 982 women and 5 120 men) aged ≥ 45 years and free from these diseases at baseline. All these individuals were recruited between 1990 and 2016 into the prospective population-based Rotterdam Study. At the end of their analyzes, the authors concluded that one in two women and one in three men will develop dementia, stroke or parkinsonism during their lifetime, and that the risk for women to develop both stroke and dementia during their life is almost twice that of men [1].
    By reading the article from Licher et al. [1], we were extremely surprised by the fact that the authors did not consider the impact of the difference in life expectancies between men and women on their results and conclusions. This is particularly well underlined by the fact that the authors did not clearly precise the age structures of the two populations they studied [1]. In our view, this information is critical as, although the reasons for this difference are still debated and may probably be multi-factorial [2], it is well known that women live longer than men. This trend is confirmed by the 2018 World Health Statistics report [3] that estimates that in 2016, the life expectancies of men and women at birth were respectively 69.8 and 74.2 years at the international level. The...

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  • The complex NMDAR-antibody associated movement disorder is highly-distinctive

    We thoroughly enjoyed reading the comment on our paper which analysed expert ratings of the movement disorder associated with NMDAR antibody-encephalitis.1 Thompson et al’s elegant pathophysiological explanation provides an excellent framework of the most plausible neural structures involved in NMDAR-antibody encephalitis. Further, they note these movements can occur in semi-conscious patients, and this concurs well with the previous description of anti-gravity movements in the context of ‘status dissociatus’.2 A review of our 76 videos, revealed Thompson et al’s account of “variable, complex jerky semi-rhythmic movements….in the obtunded state” in 45 (59%) of cases. Therefore, this complex description was not present in almost half of patients. Furthermore, our recent clinical experiences note some NMDAR-antibody patients with abnormal movements but without obtundation: perhaps, given the known stepwise progression of many cases, this is a function of increasingly early disease recognition.3

    By contrast to Thompson et al, our published study design intentionally used conventional phenomenological terms to define the movement disorder associated with NMDAR antibody-encephalitis.1 This approach aimed to define a pragmatic method, available to all clinicians, which could identify and faithfully communicate this complex movement disorder, with the important aim of earlier disease recognition. The results identified a dominant set of recognised classifications – dyston...

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  • Reply to: The Movement disorder associated with NMDAR antibody-encephalitis is complex and characteristic: an expert video-rating study

    We read with interest the description of the movement disorder manifestations in patients with N-methyl-D-aspartate receptor antibody mediated encephalitis (NMDAR-AbE) by a panel of movement disorders experts (1). The authors conclude that the co-existence of dystonia, chorea and stereotypies within the same patient, variability in phenomenology within the course of a single day and evolution over time, are helpful pointers to the diagnosis of NMDAR-AbE and therefore early treatment. We agree with this conclusion. However, this analysis overlooks consideration of the distinctive, if not unique, phenomenology of the “classical” movement disorder of NMDAR-AbE (2).

    In our earlier description of this complex movement disorder we reported the presence of variable, complex, jerky semi-rhythmic bulbar and limb movements, associated with posturing and oculogyric crises, but in summarising the overall clinical syndrome we deliberately avoided conventional movement disorder terms because none captured the entire clinical picture (2). Classification of a movement disorder, particularly when complex, is guided by the most obvious, dominant or overwhelming clinical feature. The ‘classical’ movement disorder in NMDAR-AbE is complex but as acknowledged by the expert reviewers, is not typical of any of the movement disorder categories (1). Stereotypies are purposeless repetitive motor behaviours that occur when awake and are interrupted by a shift in attention or distraction. Dy...

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  • Snack Shacks, Statin Islands, and Brain Bleeds

    The interplay among statins, serum cholesterol, and spontaneous intracerebral hemorrhage (ICH) with and without prior history of ischemic stroke is controversial.

    Studies over the last decade, like the GERFHS study,[1] have concluded that increasing serum cholesterol levels may decrease the risk of ICH. This finding was confirmed in one of the largest observational studies[2] which estimated an adjusted hazard ratio (HR) of 0.94 (0.92-0.96) with every 10 mg increase in baseline serum total cholesterol level. Similar interaction was observed with increasing LDL cholesterol quartiles (LDL > 168 mg/dL; HR 0.53 [0.45-0.63]).[2]

    However, the evidence on the effect of statins in ICH is less clear. Studies ranging from the SPARCL trial[3] which showed an increased risk of recurrent ICH with high dose statins to the recent meta-analysis by Ziff et al.,[4] which described no significant increase of the risk of ICH with statins, are few examples. Similar non-significant trends were seen in the risk of ICH after prior ischemic stroke and prior ICH.[3] Prior retrospective studies also described a neutral effect of statins on recurrent ICH. Interestingly, analysis from the largest administrative database in Israel[2] showed a surprising result; statin use might be associated with decreased ICH risk. Furthermore, an indirect, albeit unique measurement of dose-response using average atorvastatin equivalent daily dose (AAEDD) churned out interesting figures – a HR of 0....

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  • A response from Noble et al. to e-letter by the Psychology Task Force of the International League Against Epilepsy

    Dear Editor,
    Re: A response from Noble et al. to e-letter by Psychology Task Force of the International League Against Epilepsy
    Cognitive behavioural therapy (CBT) has been recommended for treating depression in people with epilepsy (PWE).[1, 2] The clinical significance of the effects of CBT for PWE has though, not been considered. We therefore systematically searched the literature for randomised controlled trials of CBT for PWE [3] and used Jacobson’s criteria [4] to empirically determine whether PWE made clinically reliable improvement. We compared this to that seen in the control arms of these trials.
    Our main findings were that the likelihood of statistically reliable improvement in symptoms of depression was significantly higher for those PWE randomised to CBT compared to control conditions. The overall proportion of PWE achieving reliable improvement was low – 30% compared to 10% in the control arms. For most PWE, symptoms were unchanged.
    The proportion of PWE who improve following CBT is limited. It should serve as a clarion call for the development of more effective treatments. Indeed, our review may have inflated CBT’s benefit since some trials included PWE without clinical distress at baseline and so it was not possible to apply Jacobson’s second, more stringent criterion and calculate for what proportion CBT also resulted in recovery.
    The Psychology Task Force of the International League Against Epilepsy submitted a response to ou...

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  • Response to a letter by Dr. G. Banerjee

    We read with great interest the recent report of Banerjee and colleagues of three cases of minimally symptomatic cerebral amyloid angiopathy-related inflammation (CAA-ri) cases, drawing attention to the possibility of a wider spectrum of clinical manifestations in patients with CAA-ri than previously described1.
    Cerebral amyloid angiopathy-related inflammation (CAA-ri) is a rare form of meningoencephalitis, presenting acutely with cognitive decline, seizures, headache and /or encephalopathy in most patients. The prognosis is poor even in patients under immunosuppressive treatment, with a mortality rate of 30% and only a minority of patients making a full recovery2-3. However, in the three cases reported by Banerjee and colleagues, patients presented with mild symptoms despite the magnitude of the MRI findings and made a full clinical and radiologic recovery in 2 of the cases with immunosuppressant treatment and in the remaining without any treatment.
    We have recently evaluated a similar patient, that presented with mild transient symptoms in whom the diagnosis was made following the finding of characteristic CAA-ri changes in brain MRI.
    He was a 62 year-old-man with a past history of hypertension, who was referred to the Emergency Department (ER) due to moderate frontal headache followed by left hemisensory numbness with Jacksonian march lasting a few minutes. He was asymptomatic on arrival at the ER and his neurological examination was normal. He perfor...

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  • Area postrema syndrome: another feature of anti-GFAP encephalomyelitis

    Dear Editor,

    We read with great interest the recent paper of Sechi et al. that describes 13 patients with anti-GFAP related myelitis and compares them with 41 patients with anti-AQP4 related myelitis.1 To date, very little data is available about anti-GFAP related disorders.2-3 Sechi et al. highlight some differences between the two entities to help clinicians differentiate them.1 One of these clinical differences relates to area postrema syndrome (APS). Indeed, it is well known that APS is a classical feature of neuromyelitis optica spectrum disorders, particularly among anti-AQP4 positive patients.4 Sechi et al. report this syndrome as a prodromal event in 20% of anti-AQP4 related myelitis. Conversely, the authors do not report any case of APS preceding or accompanying myelitis related to anti-GFAP.1 Given these data, APS could be an indicator for ruling out anti-GFAP encephalomyelitis, particularly useful for centers that do not yet have access to biological testing for anti-GFAP Abs.
    However, we report the case of a 41-year-old woman who in April 2016 developed intractable nausea and vomiting lasting for five weeks and leading to 35 kilograms in weight loss. An extensive search for a digestive disease was negative, and no neurological explorations were performed. One month following the resolution of digestive symptoms, she developed mental confusion, diplopia, dysarthria, dizziness, bilateral blurred vision (with optic disc edema) and paraparesis. Brain...

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  • Models for predicting risk of dementia: improvement still needed

    Hou et al. are to be commended for an in-depth systematic review of currently available dementia risk models that quantify the probability of developing dementia, covering both studies on community-dwelling individuals as well as clinic-based MCI studies.1 One of the key conclusions was that “the predictive ability of existing dementia risk models is acceptable, but the lack of validation limited the extensive application of the models for dementia risk prediction in general population or across subgroups in the population.” Based on recent insights, we believe that the discriminative ability of existing dementia prediction models in the general population is currently not acceptable for clinical use.

    We recently validated four promising dementia risk models (CAIDE, ANU-ADRI, BDSI, and DRS).2 In addition to external validation of these models in the Dutch general population, we also sought to investigate how these models compared to predicting dementia based on the age component of these models only. We found that full models do not have better discriminative properties than age alone. As such, we would like to make three suggestions to establish a reliable dementia prediction model.

    First, prediction models typically only report model performance on the basis of a full model.1-4 For dementia risk, however, age plays a pivotal role. Therefore, any new model should compare its predictive accuracy to age alone.

    Second, the setting in which a prediction...

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