BackgroundThe anti-seizure medication vigabatrin (VGB) is effective for controlling seizures, esp... more BackgroundThe anti-seizure medication vigabatrin (VGB) is effective for controlling seizures, especially infantile spasms. However, use is limited by VGB-associated visual field loss (VAVFL). The mechanisms by which VGB causes VAVFL remains unknown. Average peripapillary retinal nerve fibre layer (ppRNFL) thickness correlates with the degree of visual field loss (measured by mean radial degrees). Duration of VGB exposure, maximum daily VGB dose, and male sex are associated with ppRNFL thinning. Here we test the hypothesis that common genetic variation is a predictor of ppRNFL thinning in VGB exposed individuals. Identifying pharmacogenomic predictors of ppRNFL thinning in VGB exposed individuals could potentially enable safe prescribing of VGB and broader use of a highly effective drug.MethodsOptical coherence topography (OCT) and GWAS data were processed from VGB-exposed individuals (n = 71) recruited through the EpiPGX Consortium. We conducted quantitative GWAS analyses for the fo...
Progressive myoclonus epilepsy type 1 of Unverricht-Lundborg (EPM1) is a rare disorder, associate... more Progressive myoclonus epilepsy type 1 of Unverricht-Lundborg (EPM1) is a rare disorder, associated with mutations in the cystatin B (CSTB) gene. The most prevalent molecular abnormality is an expansion of a dodecamer repeat in the promoter region of the CSTB gene, but point mutations in the CSTB gene have also been found. DNA examination may be useful in discriminating EPM1 from juvenile myoclonic epilepsy, and from other types of progressive myoclonus epilepsy. An early diagnosis is important to optimise treatment and to provide an adequate prognosis and prediction of recurrence.
A 76-year-old man suffering from myelofibrosis with thrombocytopenia sustained an acute subdural ... more A 76-year-old man suffering from myelofibrosis with thrombocytopenia sustained an acute subdural haematoma with severe neurological deficit. He was treated initially by bedrest and dexamethasone. Craniotomy was contraindicated because his bleeding time exceeded 20 min in spite of multiple infusions of platelet concentrate. After 3 weeks his condition deteriorated with increase of the fluid collection shown by CT. Partial drainage of the haematoma by subdural puncture with a 22-gauge spinal needle resulted in complete recovery from the neurological deficit and complete resorption of the effusion. The case shows that it is possible to avoid craniotomy in the acute phase of a subdural haematoma in patients with bleeding disorders and that it may be advantageous to use needle evacuation instead of burr-hole drainage in the chronic phase.
We analysed the clinical phenotypes, evolution, and genetics of a large family presented through ... more We analysed the clinical phenotypes, evolution, and genetics of a large family presented through a single proband who suffered increasingly from jerks in her jaw especially when speaking in front of the classroom and who appeared to be photosensitive, both clinically and in EEG recordings. The proband was then investigated by Whole Exome Sequencing, which identified 4 novel, predicted damaging mutations in different genes, all located in one of the four linkage peaks. An Arg267Cys mutation in the SCNM1 gene was carried in heterozygous state in all photosensitive family members. The gene regulates splicing of voltage gated ion channels and the mutation indeed affected the level of splicing of the SCN1A splice variant that was also carried by 7 of the affected family members. No other SCNM1 mutations were found in unrelated PPR European patients, suggesting that SCNM1 is a private mutation of this family and may be causing this unique combination of phenotypes
To assess effectiveness and tolerability of first-line and conversion to lacosamide monotherapy f... more To assess effectiveness and tolerability of first-line and conversion to lacosamide monotherapy for focal seizures. Retrospective, non-interventional chart review of lacosamide monotherapy patients aged ≥16 years in Europe. Outcomes included retention rate at observational point (OP) 3 (12 ± 3 months), seizure freedom rates at OP2 (6 ± 3 months) and OP3 and adverse drug reactions (ADRs). A total of 439 patients were included (98 first-line and 341 conversion to monotherapy; 128 aged ≥65 years [25 first-line and 103 conversion to monotherapy]). First-line and conversion to monotherapy retention rates were 60.2% (59/98; 95% confidence interval [CI] 49.8%-70.0%) and 62.5% (213/341; 57.1%-67.6%), respectively. Kaplan-Meier estimates of 12-month retention rates were 81.2% and 91.4% for first-line and conversion to monotherapy, respectively. First-line and conversion to monotherapy retention rates in patients aged ≥65 years were 60.0% (38.7%-78.9%) and 68.9% (59.1%-77.7%), respectively. A...
Op 19 december 2022 vond in Utrecht de promotie plaats van Bianca Berghuis, op een proefschrift g... more Op 19 december 2022 vond in Utrecht de promotie plaats van Bianca Berghuis, op een proefschrift getiteld: Carbamazepine en Oxcarbazepine Induced Hyponatremia.
BackgroundThe anti-seizure medication vigabatrin (VGB) is effective for controlling seizures, esp... more BackgroundThe anti-seizure medication vigabatrin (VGB) is effective for controlling seizures, especially infantile spasms. However, use is limited by VGB-associated visual field loss (VAVFL). The mechanisms by which VGB causes VAVFL remains unknown. Average peripapillary retinal nerve fibre layer (ppRNFL) thickness correlates with the degree of visual field loss (measured by mean radial degrees). Duration of VGB exposure, maximum daily VGB dose, and male sex are associated with ppRNFL thinning. Here we test the hypothesis that common genetic variation is a predictor of ppRNFL thinning in VGB exposed individuals. Identifying pharmacogenomic predictors of ppRNFL thinning in VGB exposed individuals could potentially enable safe prescribing of VGB and broader use of a highly effective drug.MethodsOptical coherence topography (OCT) and GWAS data were processed from VGB-exposed individuals (n = 71) recruited through the EpiPGX Consortium. We conducted quantitative GWAS analyses for the fo...
Progressive myoclonus epilepsy type 1 of Unverricht-Lundborg (EPM1) is a rare disorder, associate... more Progressive myoclonus epilepsy type 1 of Unverricht-Lundborg (EPM1) is a rare disorder, associated with mutations in the cystatin B (CSTB) gene. The most prevalent molecular abnormality is an expansion of a dodecamer repeat in the promoter region of the CSTB gene, but point mutations in the CSTB gene have also been found. DNA examination may be useful in discriminating EPM1 from juvenile myoclonic epilepsy, and from other types of progressive myoclonus epilepsy. An early diagnosis is important to optimise treatment and to provide an adequate prognosis and prediction of recurrence.
A 76-year-old man suffering from myelofibrosis with thrombocytopenia sustained an acute subdural ... more A 76-year-old man suffering from myelofibrosis with thrombocytopenia sustained an acute subdural haematoma with severe neurological deficit. He was treated initially by bedrest and dexamethasone. Craniotomy was contraindicated because his bleeding time exceeded 20 min in spite of multiple infusions of platelet concentrate. After 3 weeks his condition deteriorated with increase of the fluid collection shown by CT. Partial drainage of the haematoma by subdural puncture with a 22-gauge spinal needle resulted in complete recovery from the neurological deficit and complete resorption of the effusion. The case shows that it is possible to avoid craniotomy in the acute phase of a subdural haematoma in patients with bleeding disorders and that it may be advantageous to use needle evacuation instead of burr-hole drainage in the chronic phase.
We analysed the clinical phenotypes, evolution, and genetics of a large family presented through ... more We analysed the clinical phenotypes, evolution, and genetics of a large family presented through a single proband who suffered increasingly from jerks in her jaw especially when speaking in front of the classroom and who appeared to be photosensitive, both clinically and in EEG recordings. The proband was then investigated by Whole Exome Sequencing, which identified 4 novel, predicted damaging mutations in different genes, all located in one of the four linkage peaks. An Arg267Cys mutation in the SCNM1 gene was carried in heterozygous state in all photosensitive family members. The gene regulates splicing of voltage gated ion channels and the mutation indeed affected the level of splicing of the SCN1A splice variant that was also carried by 7 of the affected family members. No other SCNM1 mutations were found in unrelated PPR European patients, suggesting that SCNM1 is a private mutation of this family and may be causing this unique combination of phenotypes
To assess effectiveness and tolerability of first-line and conversion to lacosamide monotherapy f... more To assess effectiveness and tolerability of first-line and conversion to lacosamide monotherapy for focal seizures. Retrospective, non-interventional chart review of lacosamide monotherapy patients aged ≥16 years in Europe. Outcomes included retention rate at observational point (OP) 3 (12 ± 3 months), seizure freedom rates at OP2 (6 ± 3 months) and OP3 and adverse drug reactions (ADRs). A total of 439 patients were included (98 first-line and 341 conversion to monotherapy; 128 aged ≥65 years [25 first-line and 103 conversion to monotherapy]). First-line and conversion to monotherapy retention rates were 60.2% (59/98; 95% confidence interval [CI] 49.8%-70.0%) and 62.5% (213/341; 57.1%-67.6%), respectively. Kaplan-Meier estimates of 12-month retention rates were 81.2% and 91.4% for first-line and conversion to monotherapy, respectively. First-line and conversion to monotherapy retention rates in patients aged ≥65 years were 60.0% (38.7%-78.9%) and 68.9% (59.1%-77.7%), respectively. A...
Op 19 december 2022 vond in Utrecht de promotie plaats van Bianca Berghuis, op een proefschrift g... more Op 19 december 2022 vond in Utrecht de promotie plaats van Bianca Berghuis, op een proefschrift getiteld: Carbamazepine en Oxcarbazepine Induced Hyponatremia.
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Papers by Gerrit-Jan de Haan