621 e-Letters

  • Treatment for patients with progressive supranuclear palsy

    Malpetti et al. examined neuroinflammation in subcortical regions for predicting clinical progression in patients with progressive supranuclear palsy (PSP) (1). Principal component analysis (PCA) was applied for the analysis, and neuroinflammation and tau burden in the brainstem and cerebellum significantly correlated with the subsequent annual rate of change in the score of Progressive Supranuclear Palsy Rating Scale. Namely, PCA-derived [11C]PK11195 positron emission tomography (PET) markers of neuroinflammation and tau pathology significantly correlated with regional brain volume, but MRI volumes alone did not predict the clinical progression. I present some information with special reference to treatment strategies.

    As there are no modifiable lifestyle factors to suppress progression of PSP (2), keeping quality of life by symptom-controlling medications has been recommended. Morgan et al. reported that symptomatic medications, most often for parkinsonism and depression, were prescribed for 87% of patients with PSP, whose satisfaction was poor in most cases (3). Although there have been no effective neuroprotective therapies and/or disease-modifying agents for patients with tauopathies and synucleinopathies, Jabbari et al. recently identified that genetic variation at the leucine-rich repeat kinase 2 (LRRK2) locus was significantly associated with survival in PSP, which might be based on the effect of long noncoding RNA on LRRK2 expression (4). As LRRK2 is associ...

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  • The link between CLIPPERS and lymphoma might be not fortuitous

    We read with great interest the article written by Sofia Doubrovinskaia and colleagues, entitled“Primary CNS lymphoma after CLIPPERS: A case series.”1
    CLIPPERS mimics are numerous (e.g. primary angiitis of the central nervous system, autoimmune gliopathies [related to anti-myelin oligodendrocyte glycoprotein or anti-glial fibrillary acidic protein antibodies], Erdheim-Chester disease, systemic lymphoma, and primary central nervous system lymphoma [PCNSL]).2
    Among these mimics, only patients who eventually developed a PCNSL (EBV-driven or not) fulfilled initially all CIPPERS criteria, including histological features on brain biopsy (i.e. definite CLIPPERS). In this subset of patients, a question arises: is CLIPPERS a prelymphoma state or a paralymphomatous immune response?
    1) Some clues suggest that paralymphomatous immune response seems to be the most likely hypothesis.
    1.1) In all reported patients who eventually developed PCNSL, histological findings at the first brainstem attack fulfilled histological criterion for CLIPPERS (i.e. characteristic perivascular lymphohistiocytic infiltrates with predominance of T4-cells) with no evidence of lymphoma (i.e. atypical or large B-cells and absence of EBV in B-cells).
    1.2) In these patients, while enhancing lesions predominated initially in the pons, as usually described in CLIPPERS, some of them developed PCNSL remote from the brainstem (i.e. periventricular regions).
    1.3) Besides PCNSL, defin...

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  • Carotid web: stroke trigger in young patients with COVID-19 and without cardiovascular risk factors?

    We read with great interest the recent article by Mac Grory et al.1 The authors conducted a comprehensive review on the carotid network as a possible chain factor of cryptogenic embolic stroke, particularly in young patients without risk factors. This condition accounts for approximately 25% of ischemic strokes and has less severe sequelae than other forms of strokes, making the topic of the association of stroke and other diseases interesting to open discussion, in order to intervene and prevent serious recurrent strokes that will lead to irreversible sequelae.1

    The carotid network is defined as a fibromuscular dysplasia of the intima in the carotid arteries, which causes a deficiency in intraluminal filling along the posterior wall of the carotid bulb, this can be observed through imaging such as ultrasound or CT angiography.2 This pathological entity has been reported as a sub diagnostic,2 because it is little known and does not have the epidemiological impact it should have, even more so because most sufferers are asymptomatic.3 Although there are studies that state that this condition occurs more frequently in a population < 55 years (average 45 - 50 years)4, there are cohorts that report cases near 30 years. In addition, another aspect to highlight is that these studies are carried out mainly in developed countries, so the epidemiological distribution of this condition in low- and middle-income countries is not clearly known, who possess genetic characteris...

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  • Supporting IIH patients through the COVID-19 pandemic

    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.


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  • Dopaminergic abnormalities after subarachnoid haemorrhage

    We read with great interest the study by Jenkins et al 1. Using dopamine transporter (DAT) 123I- Ioflupane SPECT imaging, the authors provide evidence for different patterns of dopaminergic abnormalities in patients with traumatic brain injury (TBI) and patients with Parkinson’s disease.
    We would like to report on the clinical observation of a 35-year-old patient who was admitted at our institution after an aneurysmal subarachnoid haemorrhage (SAH). The patient was initially comatose, and the CT-scan revealed an intraparenchymal haemorrhage associated with an intraventricular haemorrhage. The patient was treated with endovascular treatment and a ventricular catheter was inserted to treat SAH-associated hydrocephalus. There were no ischemic complications. Upon awakening, we observed a bilateral postural tremor affecting the upper limbs, which had already been noticed by the relatives before SAH. The patient’s father is deceased but also had a history of tremor. Our initial conclusion was that this tremor was compatible with essential tremor and required no further investigation.
    After ventriculoperitoneal shunting for hydrocephalus (complicated by overdrainage) the patient made a progressive recovery and returned to part-time work as a gardener despite the persistence of cognitive symptoms.
    One year after haemorrhage, the amplitude of the postural tremor decreased, and a dystonia affecting the right hand appeared. Upon examination 21 months after haemorr...

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  • Response to: COVID-19 associated Myasthenic crisis

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

  • Chronic inflammatory axonal polyneuropathy

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

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

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

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  • COVID-19 associated Myasthenic crisis

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

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

    To the Editor

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

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

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

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