Publications by authors named "Katri Silvennoinen"

9 Publications

  • Page 1 of 1

Two-center experience of cannabidiol use in adults with Dravet syndrome.

Seizure 2021 May 24;91:5-8. Epub 2021 May 24.

Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, Box 29, Queen Square, London WC1N 3BG, UK; Chalfont Centre for Epilepsy, Chalfont St Peter, UK.

We describe real-world experience with cannabidiol (CBD) in adults with Dravet Syndrome (DS) via GW Pharma early access programme at two UK neurology centres. Adults with genetically-confirmed DS had CBD added to existing therapy, titrated up to 20 mg/kg, as tolerated. The primary outcome measure was percentage reduction in convulsive seizures. Secondary outcome measures included changes in myoclonic seizures, and in cognition and quality of life as assessed by the Caregiver Global Impression of Change (CGIC), and incidence of adverse events (AEs). 18 adults (7 female; median age 27.5 years; range 20-51) were included. Median follow-up was 176 days. In one, another antiseizure drug, clobazam, was introduced during the programme. 3/17 (17.6%) had >30% reduction in convulsive seizures (range: 87.5-100%). AEs occurred in all, the most common being transaminitis (52.9%). Behavioural AEs led to discontinuation in 3/18 (16.7%), including a seizure-free responder. In 7/18, CBD was stopped due to lack of effect. 8/18 continue on treatment. Improvements in CGIC were reported in 41.2% and 47.1% by physicians and families, respectively. 17.6% achieved sufficient reduction in convulsive seizure frequency to qualify for NHS funding. AEs led to withdrawal in only 16.7%. Close monitoring and dose adjustments of other antiseizure drugs were necessary.
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http://dx.doi.org/10.1016/j.seizure.2021.05.014DOI Listing
May 2021

Real-life survey of pitfalls and successes of precision medicine in genetic epilepsies.

J Neurol Neurosurg Psychiatry 2021 Apr 26. Epub 2021 Apr 26.

Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, London, and Chalfont Centre for Epilepsy, Gerrard Cross, UK

Objective: The term 'precision medicine' describes a rational treatment strategy tailored to one person that reverses or modifies the disease pathophysiology. In epilepsy, single case and small cohort reports document nascent precision medicine strategies in specific genetic epilepsies. The aim of this multicentre observational study was to investigate the deeper complexity of precision medicine in epilepsy.

Methods: A systematic survey of patients with epilepsy with a molecular genetic diagnosis was conducted in six tertiary epilepsy centres including children and adults. A standardised questionnaire was used for data collection, including genetic findings and impact on clinical and therapeutic management.

Results: We included 293 patients with genetic epilepsies, 137 children and 156 adults, 162 females and 131 males. Treatment changes were undertaken because of the genetic findings in 94 patients (32%), including rational precision medicine treatment and/or a treatment change prompted by the genetic diagnosis, but not directly related to known pathophysiological mechanisms. There was a rational precision medicine treatment for 56 patients (19%), and this was tried in 33/56 (59%) and was successful (ie, >50% seizure reduction) in 10/33 (30%) patients. In 73/293 (25%) patients there was a treatment change prompted by the genetic diagnosis, but not directly related to known pathophysiological mechanisms, and this was successful in 24/73 (33%).

Significance: Our survey of clinical practice in specialised epilepsy centres shows high variability of clinical outcomes following the identification of a genetic cause for an epilepsy. Meaningful change in the treatment paradigm after genetic testing is not yet possible for many people with epilepsy. This systematic survey provides an overview of the current application of precision medicine in the epilepsies, and suggests the adoption of a more considered approach.
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http://dx.doi.org/10.1136/jnnp-2020-325932DOI Listing
April 2021

Clinical outcomes of COVID-19 in long-term care facilities for people with epilepsy.

Epilepsy Behav 2021 02 5;115:107602. Epub 2020 Nov 5.

Department of Clinical & Experimental Epilepsy, UCL Queen Square Institute of Neurology, London WC1N 3BG, UK; Chalfont Centre for Epilepsy (CCE), Chalfont St Peter, Bucks SL9 0RJ, UK.

In this cohort study, we aim to compare outcomes from coronavirus disease 2019 (COVID-19) in people with severe epilepsy and other co-morbidities living in long-term care facilities which all implemented early preventative measures, but different levels of surveillance. During 25-week observation period (16 March-6 September 2020), we included 404 residents (118 children), and 1643 caregivers. We compare strategies for infection prevention, control, and containment, and related outcomes, across four UK long-term care facilities. Strategies included early on-site enhancement of preventative and infection control measures, early identification and isolation of symptomatic cases, contact tracing, mass surveillance of asymptomatic cases and contacts. We measured infection rate among vulnerable people living in the facilities and their caregivers, with asymptomatic and symptomatic cases, including fatality rate. We report 38 individuals (17 residents) who tested severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive, with outbreaks amongst residents in two facilities. At Chalfont Centre for Epilepsy (CCE), 10/98 residents tested positive: two symptomatic (one died), eight asymptomatic on weekly enhanced surveillance; 2/275 caregivers tested positive: one symptomatic, one asymptomatic. At St Elizabeth's (STE), 7/146 residents tested positive: four symptomatic (one died), one positive during hospital admission for symptoms unrelated to COVID-19, two asymptomatic on one-off testing of all 146 residents; 106/601 symptomatic caregivers were tested, 13 positive. In addition, during two cycles of systematically testing all asymptomatic carers, four tested positive. At The Meath (TM), 8/80 residents were symptomatic but none tested; 26/250 caregivers were tested, two positive. At Young Epilepsy (YE), 8/80 children were tested, all negative; 22/517 caregivers were tested, one positive. Infection outbreaks in long-term care facilities for vulnerable people with epilepsy can be quickly contained, but only if asymptomatic individuals are identified through enhanced surveillance at resident and caregiver level. We observed a low rate of morbidity and mortality, which confirmed that preventative measures with isolation of suspected and confirmed COVID-19 residents can reduce resident-to-resident and resident-to-caregiver transmission. Children and young adults appear to have lower infection rates. Even in people with epilepsy and multiple co-morbidities, we observed a high percentage of asymptomatic people suggesting that epilepsy-related factors (anti-seizure medications and seizures) do not necessarily lead to poor outcomes.
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http://dx.doi.org/10.1016/j.yebeh.2020.107602DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643621PMC
February 2021

Complex epilepsy: it's all in the history.

Pract Neurol 2020 Oct 17. Epub 2020 Oct 17.

Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, London, UK

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http://dx.doi.org/10.1136/practneurol-2020-002522DOI Listing
October 2020

Transcranial magnetic stimulation as a tool to understand genetic conditions associated with epilepsy.

Epilepsia 2020 09 12;61(9):1818-1839. Epub 2020 Aug 12.

Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, London, UK.

Advances in genetics may enable a deeper understanding of disease mechanisms and promote a shift to more personalised medicine in the epilepsies. At present, understanding of consequences of genetic variants mainly relies on preclinical functional work; tools for acquiring similar data from the living human brain are needed. Transcranial magnetic stimulation (TMS), in particular paired-pulse TMS protocols which depend on the function of cortical GABAergic interneuron networks, has the potential to become such a tool. For this report, we identified and reviewed 23 publications on TMS studies of cortical excitability and inhibition in 15 different genes or conditions relevant to epilepsy. Reduced short-interval intracortical inhibition (SICI) and reduced cortical silent period (CSP) duration were the most commonly reported findings, suggesting abnormal GABA - (SICI) or GABA ergic (CSP) signalling. For several conditions, these findings are plausible based on established evidence of involvement of the GABAergic system; for some others, they may inform future research around such mechanisms. Challenges of TMS include lack of complete understanding of the neural underpinnings of the measures used: hypotheses and analyses should be based on existing clinical and preclinical data. Further pitfalls include gathering sufficient numbers of participants, and the effect of confounding factors, especially medications. TMS-EEG is a unique perturbational technique to study the intrinsic properties of the cortex with excellent temporal resolution; while it has the potential to provide further information of use in interpreting effects of genetic variants, currently the links between measures and neurophysiology are less established. Despite these challenges, TMS is a tool with potential for elucidating the system-level in vivo functional consequences of genetic variants in people carrying genetic changes of interest, providing unique insights.
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http://dx.doi.org/10.1111/epi.16634DOI Listing
September 2020

Comparative effectiveness of antiepileptic drugs in juvenile myoclonic epilepsy.

Epilepsia Open 2019 Sep 4;4(3):420-430. Epub 2019 Jul 4.

Department of Neurology Hôpital Erasme, Université Libre de Bruxelles Brussels Belgium.

Objective: To study the effectiveness and tolerability of antiepileptic drugs (AEDs) commonly used in juvenile myoclonic epilepsy (JME).

Methods: People with JME were identified from a large database of individuals with epilepsy, which includes detailed retrospective information on AED use. We assessed secular changes in AED use and calculated rates of response (12-month seizure freedom) and adverse drug reactions (ADRs) for the five most common AEDs. Retention was modeled with a Cox proportional hazards model. We compared valproate use between males and females.

Results: We included 305 people with 688 AED trials of valproate, lamotrigine, levetiracetam, carbamazepine, and topiramate. Valproate and carbamazepine were most often prescribed as the first AED. The response rate to valproate was highest among the five AEDs (42.7%), and significantly higher than response rates for lamotrigine, carbamazepine, and topiramate; the difference to the response rate to levetiracetam (37.1%) was not significant. The rates of ADRs were highest for topiramate (45.5%) and valproate (37.5%). Commonest ADRs included weight change, lethargy, and tremor. In the Cox proportional hazards model, later start year (1.10 [1.08-1.13],  < 0.001) and female sex (1.41 [1.07-1.85],  = 0.02) were associated with shorter trial duration. Valproate was associated with the longest treatment duration; trials with carbamazepine and topiramate were significantly shorter (HR [CI]: 3.29 [2.15-5.02],  < 0.001 and 1.93 [1.31-2.86],  < 0.001). The relative frequency of valproate trials shows a decreasing trend since 2003 while there is an increasing trend for levetiracetam. Fewer females than males received valproate (76.2% vs 92.6%,  = 0.001).

Significance: In people with JME, valproate is an effective AED; levetiracetam emerged as an alternative. Valproate is now contraindicated in women of childbearing potential without special precautions. With appropriate selection and safeguards in place, valproate should remain available as a therapy, including as an alternative for women of childbearing potential whose seizures are resistant to other treatments.
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http://dx.doi.org/10.1002/epi4.12349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6698679PMC
September 2019

Drug-resistant epilepsy, early-onset hypertension and white matter lesions: a hidden paraganglioma.

BMJ Case Rep 2019 Jun 21;12(6). Epub 2019 Jun 21.

Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of Neurology, London, UK.

We describe the case of a 35-year-old man with focal epilepsy since age 16. Due to a refractory course, several treatments were tried over the years, including insertion of a deep brain stimulator. At the time of his first assessment at our unit, he had recently been diagnosed with hypertension. An MR scan of brain revealed multiple T2 hyperintense white matter lesions, and evidence of previous haemorrhage in the left basal ganglia and pons. On follow-up imaging, the changes were considered to be in keeping with hypertensive arteriopathy. He was referred for further assessment of his hypertension and was found to have a para-aortic paraganglioma. This was excised 16 months after his initial presentation to us. The surgery was associated with an improvement in his seizure control. This case serves as a reminder of the need to be vigilant about the possibility of coexisting conditions in people with epilepsy.
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http://dx.doi.org/10.1136/bcr-2018-228348DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6605913PMC
June 2019

Non-invasive electric current stimulation for restoration of vision after unilateral occipital stroke.

Contemp Clin Trials 2015 Jul 11;43:231-6. Epub 2015 Jun 11.

Institute of Medical Psychology, University of Magdeburg, Medical Faculty, Magdeburg 39120, Germany.

Occipital stroke often leads to visual field loss, for which no effective treatment exists. Little is known about the potential of non-invasive electric current stimulation to ameliorate visual functions in patients suffering from unilateral occipital stroke. One reason is the traditional thinking that visual field loss after brain lesions is permanent. Since evidence is available documenting vision restoration by means of vision training or non-invasive electric current stimulation future studies should also consider investigating recovery processes after visual cortical strokes. Here, protocols of repetitive transorbital alternating current stimulation (rtACS) and transcranial direct current stimulation (tDCS) are presented and the European consortium for restoration of vision (REVIS) is introduced. Within the consortium different stimulation approaches will be applied to patients with unilateral occipital strokes resulting in homonymous hemianopic visual field defects. The aim of the study is to evaluate effects of current stimulation of the brain on vision parameters, vision-related quality of life, and physiological parameters that allow concluding about the mechanisms of vision restoration. These include EEG-spectra and coherence measures, and visual evoked potentials. The design of stimulation protocols involves an appropriate sham-stimulation condition and sufficient follow-up periods to test whether the effects are stable. This is the first application of non-invasive current stimulation for vision rehabilitation in stroke-related visual field deficits. Positive results of the trials could have far-reaching implications for clinical practice. The ability of non-invasive electrical current brain stimulation to modulate the activity of neuronal networks may have implications for stroke rehabilitation also in the visual domain.
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http://dx.doi.org/10.1016/j.cct.2015.06.005DOI Listing
July 2015

Do-not-resuscitate (DNR) orders in patients with intracerebral hemorrhage.

Int J Stroke 2014 Jan 22;9(1):53-8. Epub 2013 Oct 22.

Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland.

Background And Purpose: Do-not-resuscitate orders may be associated with poor outcome in patients with intracerebral hemorrhage because of less active management.

Aims: We sought to characterize the practice of issuing do-not-resuscitate orders in intracerebral hemorrhage. We also aimed to identify possible differences in care according to do-not-resuscitate status.

Methods: We conducted a retrospective study of all consecutive intracerebral hemorrhage patients admitted to the Meilahti Hospital of the Helsinki University Central Hospital between January 2005 and March 2010. Data obtained from medical records allowed comparison of characteristics of patients and care of do-not-resuscitate and non-do-not-resuscitate patients as well as patients with early (within 24 h) and late (>24 h) do-not-resuscitate decisions. Logistic regression was used to identify factors independently associated with do-not-resuscitate decisions.

Results: Of our 1013 patients, a do-not-resuscitate order was issued in 368 (35%), of which 262 (73%) occurred within 24 h from admission. Advanced age (odds ratio 1·06 per year; 95% confidence interval 1·04-1·08), more severe stroke (1·09 per National Institutes of Health Stroke Scale point; 1·06-1·13), and deterioration soon after admission (5·12, 3·33-7·87) had the strongest associations with do-not-resuscitate decisions. Patients with do-not-resuscitate orders received recommended care including stroke unit care (43% vs. 64%; P < 0·001) and prophylaxis for deep venous thrombosis (45% vs. 54%; P = 0·027) less often than non-do-not-resuscitate patients. This was especially the case when the do-not-resuscitate order was issued early.

Conclusions: In addition to confirming the role of known intracerebral hemorrhage prognostic factors in do-not-resuscitate decision-making, our results demonstrate that do-not-resuscitate orders led to less active care of intracerebral hemorrhage patients.
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http://dx.doi.org/10.1111/ijs.12161DOI Listing
January 2014