A New Case Series Suggests That SCA48 (ATX/STUB1) Is Primarily a Monogenic Disorder.

BACKGROUND: Monoallelic, pathogenic STUB1 variants cause autosomal dominant cerebellar ataxia (ATX-STUB1/SCA48). Recently, a genetic interaction between STUB1 variants and intermediate or high-normal CAG/CAA repeats in TBP was suggested, indicating digenic inheritance or a disease-modifying role for TBP expansions. OBJECTIVE: To determine the presence and impact of intermediate or high-normal TBP expansions in ataxic patients with heterozygous STUB1 variants. METHODS: We describe 21 patients with ataxia carrying a heterozygous STUB1 variant and determined TBP repeat length. RESULTS: A total of 15 of 21 patients (71%) carried a normal TBP<40 allele, 4 (19%) carried an intermediate TBP41-42 allele, and two carried a high-normal TBP40 allele (9.5%). Five of six carriers (83%) of both STUB1 variants and TBP40-42 alleles showed marked cognitive impairment. CONCLUSIONS: SCA48 is predominantly a monogenic disorder, because most patients carried an isolated, heterozygous STUB1 variant and presented with the typical combined phenotype of ataxia and cognitive dysfunction. Still, co-occurrence of TBP41-42 or high-normal TBP40 alleles was relatively frequent and associated with marked cognitive defects (28.5%), suggesting a modifying effect on clinical expression in some cases. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Structured medication reviews in Parkinson's disease: pharmacists' views, experiences and needs - a qualitative study.

Background: Executing structured medication reviews (SMRs) in primary care to optimize drug treatment is considered standard care of community pharmacists in the Netherlands. Patients with Parkinson's disease (PD) often face complex drug regimens for their symptomatic treatment and might, therefore, benefit from an SMR. However, previously, no effect of an SMR on quality of life in PD was found. In trying to improve the case management of PD, it is interesting to understand if and to what extent SMRs in PD patients are of added value in the pharmacist's opinion and what are assumed facilitating and hindering factors. Objectives: To analyse the process of executing SMRs in PD patients from a community pharmacist's point of view. Design: A cross-sectional, qualitative study was performed, consisting of face-to-face semi-structured in-depth interviews. Methods: The interviews were conducted with community pharmacists who executed at least one SMR in PD, till data saturation was reached. Interviews were transcribed verbatim, coded and analysed thematically using an iterative approach. Results: Thirteen pharmacists were interviewed. SMRs in PD were considered of added value, especially regarding patient contact and bonding, individualized care and its possible effect in the future, although PD treatment is found already well monitored in secondary care. Major constraints were time, logistics and collaboration with medical specialists. Conclusion: Although community pharmacist-led SMRs are time-consuming and sometimes logistically challenging, they are of added value in primary care in general, and also in PD, of which treatment occurs mainly in secondary care. It emphasizes the pharmacist's role in PD treatment and might tackle future drug-related issues. Improvements concern multidisciplinary collaboration for optimized SMR execution and results.

Structured medication reviews in Parkinson's disease: pharmacists' views, experiences and needs Why is this research done? In Parkinson's disease (PD), drug therapy is still the most important treatment strategy. Due to disease progression, patients often face complicated medication regimens, polypharmacy, and potential drug-related problems. The execution of structured medication reviews (SMR) in primary care is considered standard care of community pharmacists in the Netherlands, aiming to optimise drug treatment. Although it might also affect clinical outcomes, we found no effect of an SMR in PD on quality of life in our previous study. In trying to improve case management of PD, we need to understand if and to what extent SMRs in PD patients are of added value in the pharmacist's opinion, and what are assumed facilitating and hindering factors. What did the researchers do? We conducted semi-structured interviews with 13 community pharmacists who recently executed ⩾1 SMR in PD. What did the researchers find? We found that SMRs in PD are considered of added value with regard to patient bonding and individualised care. By being known by the pharmacist, and vice versa, by knowing the patient's situation, future drug problems might be tackled earlier. However, executing SMRs comes with barriers, of which lack of time, logistic constraints and difficulties in cooperation with the medical specialist are the most important. What do these findings mean? Taking into account both the pharmacist's effort and additional costs when performing an SMR in the current setting, the valuable time of a pharmacist could potentially better be spent on more (cost-)effective interventions, or a structural solution should be sought for the experienced hindering factors. Since we do not doubt the importance of periodic medication optimization in complex diseases or high-risk patients, we have to focus on either improving the current setting of SMRs in PD, or searching for other strategies in which this can be achieved.

Predicting Motor Outcome and Quality of Life After Subthalamic Deep Brain Stimulation for Parkinson's Disease: The Role of Standard Screening Measures and Wearable-Data.

BACKGROUND: Standardized screening for subthalamic deep brain stimulation (STN DBS) in Parkinson's disease (PD) patients is crucial to determine eligibility, but its utility to predict postoperative outcomes in eligible patients is inconclusive. It is unknown whether wearable data can contribute to this aim. OBJECTIVE: To evaluate the utility of universal components incorporated in the DBS screening, complemented by a wearable sensor, to predict motor outcomes and Quality of life (QoL) one year after STN DBS surgery. METHODS: Consecutive patients were included in the OPTIMIST cohort study from two DBS centers. Standardized assessments included a preoperative Levodopa Challenge Test (LCT), and questionnaires on QoL and non-motor symptoms including cognition, psychiatric symptoms, impulsiveness, autonomic symptoms, and sleeping problems. Moreover, an ambulatory wearable sensor (Parkinson Kinetigraph (PKG)) was used. Postoperative assessments were similar and also included a Stimulation Challenge Test to determine DBS effects on motor function. RESULTS: Eighty-three patients were included (median (interquartile range) age 63 (56-68) years, 36% female). Med-OFF (Stim-OFF) motor severity deteriorated indicating disease progression, but patients significantly improved in terms of Med-ON (Stim-ON) motor function, motor fluctuations, QoL, and most non-motor domains. Motor outcomes were not predicted by preoperative tests, including covariates of either LCT or PKG. Postoperative QoL was predicted by better preoperative QoL, lower age, and more preoperative impulsiveness scores in multivariate models. CONCLUSION: Data from the DBS screening including wearable data do not predict postoperative motor outcome at one year. Post-DBS QoL appears primarily driven by non-motor symptoms, rather than by motor improvement.

The Effect of a Structured Medication Review on Quality of Life in Parkinson's Disease.

BACKGROUND: Drug therapy is important for controlling symptoms in Parkinson's disease (PD). However, it often results in complex medication regimens and could easily lead to drug related problems (DRP), suboptimal adherence and reduced treatment efficacy. A structured medication review (SMR) could address these issues and optimize therapy, although little is known about clinical effects in PD patients. OBJECTIVE: To analyze whether an SMR improves quality of life (QoL) in PD. METHODS: In this multicenter randomized controlled trial, half of the 202 PD patients with polypharmacy received a community pharmacist-led SMR. The control group received usual care. Assessments at baseline, and after three and six months comprised six validated questionnaires. Primary outcome was PD specific QoL [(PDQ-39; range 0 (best QoL) - 100 (worst QoL)]. Secondary outcomes were disability score, non-motor symptoms, general health status, and personal care giver's QoL. Furthermore, DRPs, proposed interventions, and implemented modifications in medication schedules were analyzed. RESULTS: No improvement in QoL was seen six months after an SMR, with a non-significant treatment effect difference of 2.09 (-0.63;4.80) in favor of the control group. No differences were found in secondary outcomes. In total, 260 potential DRPs were identified (2.6 (±1.8) per patient), of which 62% led to drug therapy optimization. CONCLUSION: In the current setting, a community pharmacist-led SMR did not improve QoL in PD patients, nor improved other pre-specified outcomes.

Impaired Visual Emotion Recognition After Minor Ischemic Stroke.

OBJECTIVE: To assess the prevalence of impaired visual emotion recognition in patients who have experienced a minor ischemic stroke in the subacute phase and to determine associated factors of impaired visual emotion recognition. DESIGN: A prospective observational study. SETTING: Stroke unit of a teaching hospital. PARTICIPANTS: Patients with minor ischemic stroke (N=112). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Patients with minor stroke underwent a neuropsychological assessment in the subacute phase for visual emotion recognition by the Ekman 60 Faces Test and for general cognition. Univariable linear regression analyses were performed to identify associated factors of emotion recognition impairment. RESULTS: In 112 minor stroke patients, we found a prevalence of 25% of impaired visual emotion recognition. This was significantly correlated with impaired general cognition. Nevertheless, 10.9% of patients with normal general cognition still had impaired emotion recognition. Mood was negatively associated. Stroke localization, hemisphere side, and sex were not associated. CONCLUSION: Impaired visual emotion recognition is found in about one-quarter of patients with minor ischemic stroke.

The Impact of Non-dopaminergic Medication on Quality of Life in Parkinson's Disease.

BACKGROUND AND OBJECTIVES: Quality of life (QoL) in Parkinson's disease (PD) depends on multiple factors. Due to PD treatment and accompanying, age-related or independent comorbidities, pill burden is often high. The relation of QoL and pharmacotherapy for comorbidities in PD has not been widely studied. This study investigated if and to what extent non-dopaminergic drugs are related to QoL in PD. Second, the impact of demographics and non-motor symptoms were evaluated. A better understanding of the impact of different non-dopaminergic drugs and polypharmacy on QoL will have added value in selecting appropriate (medication) interventions. METHODS: In a cross-sectional analysis, medication prescription data of 209 PD patients were analyzed and grouped according to the Rx-Risk comorbidity index. QoL was measured using the PDQ-39 questionnaire. Non-motor symptoms were analyzed with the Non-Motor Symptoms questionnaire. Independent factors associated with a reduced QoL were identified with a multivariate linear regression analysis. RESULTS: Non-dopaminergic drugs, subdivided into Rx-Risk comorbidity categories, were not associated with reduced QoL, except for the use of anti-epileptic drugs. However, using more daily non-dopaminergic drugs was also negatively associated with QoL, as well as female sex, increased PD severity, and more non-motor symptoms. Contraindicated non-dopaminergic medication was barely prescribed (0.4%). CONCLUSION: Non-dopaminergic drugs are frequently prescribed, and higher numbers are associated with impaired QoL in PD. However, when divided in drug types, only anti-epileptic drugs were negatively associated with QoL. In these patients, physicians might improve QoL by further optimizing the condition it was prescribed for (e.g., pain or anxiety), or managing of side effects. TRIAL REGISTRATION: Netherlands Trial Register; NL4360.

A Parkinson's Disease Patient without Corpus Callosum.

The authors report of a patient with Parkinson's disease in whom imaging revealed a complete agenesis of the corpus callosum. Although this co-occurrence is probably coincidental, this finding suggests that the bilateral degenerative changes in Parkinson's disease may occur independent of the interhemispheric connections.

Remote Lower White Matter Integrity Increases the Risk of Long-Term Cognitive Impairment After Ischemic Stroke in Young Adults.

BACKGROUND AND PURPOSE: Poststroke cognitive impairment occurs frequently in young patients with ischemic stroke (18 through 50 years of age). Accumulating data suggest that stroke is associated with lower white matter integrity remote from the stroke impact area, which might explain why some patients have good long-term cognitive outcome and others do not. Given the life expectancy of decades in young patients, we therefore investigated remote white matter in relation to long-term cognitive function. METHODS: We included all consecutive first-ever ischemic stroke patients, left/right hemisphere, without recurrent stroke or transient ischemic attack during follow-up, aged 18 through 50 years, admitted to our university medical center between 1980 and 2010. One hundred seventeen patients underwent magnetic resonance imaging scanning including a T1-weighted scan, a diffusion tensor imaging scan, and completed a neuropsychological assessment. Patients were compared with a matched stroke-free control group (age, sex, and education matched). Cognitive impairment was defined as >1.5 SD below the mean cognitive index score of controls and no cognitive impairment as ≤1 SD. Tract-Based Spatial Statistics was used to assess the white matter integrity (fractional anisotropy and mean diffusivity). RESULTS: About 11 years after ischemic stroke, lower remote white matter integrity was associated with a worse long-term cognitive performance. A lower remote white matter integrity, even in the contralesional hemisphere, was observed in cognitively impaired patients (n=25) compared with cognitively unimpaired patients (n=71). CONCLUSIONS: These findings indicate that although stroke has an acute onset, it might have long lasting effects on remote white matter integrity and thereby increases the risk of long-term cognitive impairment.

Feasibility of external rhythmic cueing with the Google Glass for improving gait in people with Parkinson's disease.

New mobile technologies like smartglasses can deliver external cues that may improve gait in people with Parkinson's disease in their natural environment. However, the potential of these devices must first be assessed in controlled experiments. Therefore, we evaluated rhythmic visual and auditory cueing in a laboratory setting with a custom-made application for the Google Glass. Twelve participants (mean age = 66.8; mean disease duration = 13.6 years) were tested at end of dose. We compared several key gait parameters (walking speed, cadence, stride length, and stride length variability) and freezing of gait for three types of external cues (metronome, flashing light, and optic flow) and a control condition (no-cue). For all cueing conditions, the subjects completed several walking tasks of varying complexity. Seven inertial sensors attached to the feet, legs and pelvis captured motion data for gait analysis. Two experienced raters scored the presence and severity of freezing of gait using video recordings. User experience was evaluated through a semi-open interview. During cueing, a more stable gait pattern emerged, particularly on complicated walking courses; however, freezing of gait did not significantly decrease. The metronome was more effective than rhythmic visual cues and most preferred by the participants. Participants were overall positive about the usability of the Google Glass and willing to use it at home. Thus, smartglasses like the Google Glass could be used to provide personalized mobile cueing to support gait; however, in its current form, auditory cues seemed more effective than rhythmic visual cues.

Lower Ipsilateral Hippocampal Integrity after Ischemic Stroke in Young Adults: A Long-Term Follow-Up Study.

BACKGROUND AND PURPOSE: Memory impairment after stroke is poorly understood as stroke rarely occurs in the hippocampus. Previous studies have observed smaller ipsilateral hippocampal volumes after stroke compared with controls. Possibly, these findings on macroscopic level are not the first occurrence of structural damage and are preceded by microscopic changes that may already be associated with a worse memory function. We therefore examined the relationship between hippocampal integrity, volume, and memory performance long after first-ever ischemic stroke in young adults. METHODS: We included all consecutive first-ever ischemic stroke patients, without hippocampal strokes or recurrent stroke/TIA, aged 18-50 years, admitted to our academic hospital between 1980 and 2010. One hundred and forty-six patients underwent T1 MPRAGE, DTI scanning and completed the Rey Auditory Verbal Learning Test and were compared with 84 stroke-free controls. After manual correction of hippocampal automatic segmentation, we calculated mean hippocampal fractional anisotropy (FA) and diffusivity (MD). RESULTS: On average 10 years after ischemic stroke, lesion volume was associated with lower ipsilateral hippocampal integrity (p<0.05), independent of hippocampal volume. In patients with a normal ipsilateral hippocampal volume (volume is less than or equal to 1.5 SD below the mean volume of controls) significant differences in ipsilateral hippocampal MD were observed (p<0.0001). However, patients with a normal hippocampal volume and high hippocampal MD did not show a worse memory performance compared with patients with a normal volume and low hippocampal MD (p>0.05). CONCLUSIONS: Patients with average ipsilateral hippocampal volume could already have lower ipsilateral hippocampal integrity, although at present with no attendant worse memory performance compared with patients with high hippocampal integrity. Longitudinal studies are needed to investigate whether a low hippocampal integrity after stroke might lead to exacerbated memory decline with increasing age.

Cognitive performance and poor long-term functional outcome after young stroke.

OBJECTIVE: To investigate the influence of cognitive performance on long-term functional outcome after ischemic stroke (IS) in young adults aged 18 through 50 years (young IS). METHODS: This study is part of a prospective cohort study among 277 stroke survivors with a young IS admitted to our department between January 1, 1980, and November 1, 2010. Functional outcome was assessed during follow-up between 2009 and 2012 with the modified Rankin Scale (mRS) and Instrumental Activities of Daily Living scale (IADL). Extensive neuropsychological investigation was performed. Logistic regression was used to calculate odds ratios (ORs) for a poor functional outcome (mRS >2 or IADL <8) for the 7 cognitive domains adjudicated for confounders. Cognitive function (continuous) as well as cognitive impairment (dichotomous) were studied. RESULTS: Only decline in working memory (OR 0.3, 95% confidence interval [CI] 0.1-0.6) was associated with poor functional outcome on the mRS. Except for decline in processing speed (OR 0.5, 95% CI 0.3-0.8) and working memory (OR 0.4, 95% CI 0.2-0.7), no relation was found with poor functional outcome on IADL. Impairment in none of the individual cognitive domains was related to long-term functional outcome, although impairment in global cognitive function was related to a poor functional outcome on the IADL (OR 4.8, 95% CI 1.7-14.0). CONCLUSIONS: On average, 11 years after young IS there was no clear relationship between long-term cognitive deficits and long-term functional outcome or IADL, stressing the need for further prospective studies with further development of sensitive measures of functional prognosis.

Poststroke Epilepsy Is Associated With a High Mortality After a Stroke at Young Age: Follow-Up of Transient Ischemic Attack and Stroke Patients and Unelucidated Risk Factor Evaluation Study.

BACKGROUND AND PURPOSE: Poststroke epilepsy is a common complication after a young stroke. We investigated the association between poststroke epilepsy and mortality. METHODS: We performed a prospective cohort study among 631 patients with a first-ever transient ischemic attack or ischemic stroke, aged 18 to 50 years. Survival analysis and Cox proportional hazard analysis were used to estimate cumulative mortality and hazard ratios for patients with and without epilepsy. RESULTS: After mean follow-up of 12.5 years (SD 8.6), 76 (12.0%) developed poststroke epilepsy. Case fatality was 27.4% for patients with poststroke epilepsy and 2.1% for those without. Poststroke epilepsy was associated with 30-day mortality (hazard ratio, 4.8; 95% confidence interval, 1.7-14.0) and long-term mortality (hazard ratio, 1.8; 95% confidence interval, 1.2-2.9). CONCLUSIONS: Epilepsy is a common problem after a young stroke and is associated with an increased short-term and long-term mortality.

Magnetic resonance imaging of the carotid artery in long-term head and neck cancer survivors treated with radiotherapy.

BACKGROUND: In head and neck cancer (HNC) patients, long-term treatment-related complications include radiotherapy (RT)-induced carotid vasculopathy and stroke. The current study investigated the magnetic resonance imaging (MRI) characteristics of the carotid wall in long-term HNC survivors treated with RT. METHODS: MRI of the carotid arteries was performed within a prospective cohort of 42 HNC patients on average 7 years after RT. Two independent radiologists assessed maximal vessel wall thickness of common and internal carotid arteries. In case of wall thickening (≥ 2 mm) the MRI signals as well as length of the thickened segment were assessed. RESULTS: Mean (SD) age of the 42 patients at baseline was 53 (13) years and mean (SD) follow-up time after RT was 6.8 (1.3) years. In total 62% were men and 60% had one or more cerebrovascular risk factors. Mean (SD) dose of RT on the common carotid arteries and internal carotid arteries was 57 Gy (11) and 61 Gy (10), respectively. Wall thickening was observed in 58% of irradiated versus 27% of non-irradiated common carotid arteries and 24% of irradiated versus 6% of non-irradiated internal carotid arteries (p < 0.05). Mean (SD) thickness of the irradiated and non-irradiated common carotid arteries was 2.5 (0.9) and 2 (0.7) mm (p = 0.02). Mean thickness of the irradiated and non-irradiated internal carotid arteries was 1.8 (0.8) and 1.5 mm (0.3) (n.s.). Mean length of the thickened vessel wall was 48 mm versus 36 mm in the irradiated versus non-irradiated common carotid arteries (p = 0.03) and 20 mm versus 15 mm in the irradiated versus non-irradiated internal carotid arteries (n.s.). No significant differences were observed for signal intensities of the vessel walls. CONCLUSIONS: Our study showed significantly more vessel wall thickening in irradiated versus non-irradiated carotid arteries years after RT for HNC, while no differences in signal intensities were observed.

Ipsilateral hippocampal atrophy is associated with long-term memory dysfunction after ischemic stroke in young adults.

Memory impairment after stroke in young adults is poorly understood. In elderly stroke survivors memory impairments and the concomitant loss of hippocampal volume are usually explained by coexisting neurodegenerative disease (e.g., amyloid pathology) in interaction with stroke. However, neurodegenerative disease, such as amyloid pathology, is generally absent at young age. Accumulating evidence suggests that infarction itself may cause secondary neurodegeneration in remote areas. Therefore, we investigated the relation between long-term memory performance and hippocampal volume in young patients with first-ever ischemic stroke. We studied all consecutive first-ever ischemic stroke patients, aged 18-50 years, admitted to our academic hospital center between 1980 and 2010. Episodic memory of 173 patients was assessed using the Rey Auditory Verbal Learning Test and the Rey Complex Figure and compared with 87 stroke-free controls. Hippocampal volume was determined using FSL-FIRST, with manual correction. On average 10 years after stroke, patients had smaller ipsilateral hippocampal volumes compared with controls after left-hemispheric stroke (5.4%) and right-hemispheric stroke (7.7%), with most apparent memory dysfunctioning after left-hemispheric stroke. A larger hemispheric stroke was associated with a smaller ipsilateral hippocampal volume (b=-0.003, P<0.0001). Longer follow-up duration was associated with smaller ipsilateral hippocampal volume after left-hemispheric stroke (b=-0.028 ml, P=0.002) and right-hemispheric stroke (b=-0.015 ml, P=0.03). Our results suggest that infarction is associated with remote injury to the hippocampus, which may lower or expedite the threshold for cognitive impairment or even dementia later in life.

Cardiovascular disease is the main cause of long-term excess mortality after ischemic stroke in young adults.

Adults with stroke at a young age (18-50 years) remain at an increased risk of death for decades. It is unclear what cause underlies this long-term excess mortality and whether this is sex and time specific. Therefore, we investigated sex-specific temporal changes in cause of death after transient ischemic attack or ischemic stroke in young adults aged 18 to 50 years. We included all 845 consecutive 30-day survivors, of a first-ever transient ischemic attack (n=261) or ischemic stroke (n=584), admitted to our hospital between 1980 and 2010. Survival status was assessed at April 1, 2013. Observed cause-specific mortality was compared with expected mortality, derived from mortality rates in the general population with similar age, sex, and calendar-year characteristics. During a median follow-up of 9.2 years, 146 patients (17.3%) died, such that 29 years of life was lost by each individual. For all causes of death, observed mortality exceeded expected mortality. The absolute excess risk of death was for 74% attributable to a vascular cause (absolute excess risk, 2.8 per 1000 person-years [95% confidence interval, 1.8-4.1] for stroke and absolute excess risk, 4.3 per 1000 person-years [95% confidence interval, 2.9-5.9] for other vascular causes). The absolute excess risk was highest between 10 and 15 years after stroke and this peak was most pronounced in men and mainly attributable to vascular death. Long-term excess death after stroke in young adults is mainly attributable to a vascular cause and most pronounced in men. Attempts to reduce the risk of vascular disease after stroke in young adults should extend beyond the acute phase into the long term.

Cognitive function, depression, fatigue and quality of life among long-term survivors of head and neck cancer.

BACKGROUND: Long-term cancer treatment complications become more prevalent as survival improves. Little is known about the psychological complications in long-term survivors of head and neck cancer (HNC). We investigated cognitive functioning and its relation with depression, fatigue, cognitive complaints, and brain lesions on MRI. METHODS: This study is part of a multicentre, prospective cohort study of 65 patients treated for HNC. A comprehensive neuropsychological assessment was combined with validated questionnaires on subjective memory complaints, depression, and fatigue after a median of 7 years follow-up. Results were compared with age- and education-adjusted normative data. Further, we evaluated cerebral white matter hyperintensities (WMH), brain volume, and infarctions on MRI. RESULTS: HNC patients had worse cognitive performance in two of the five assessed cognitive domains: episodic memory (z = -0.48, P = .003) and speed of information processing (z = -0.47, P < 0.001). Patients with fatigue performed worse than patients without fatigue on verbal fluency (mean difference in z-score 0.52, P = .02) and speed of information processing (0.49, P = .04). Patients with subjective memory complaints had a worse episodic memory performance (mean difference in z-score -0.96; P = .02). Patients with cerebral infarction(s) on MRI performed worse on fluency (mean difference in z-score 0.74, P = .005). A lower cognitive performance was not associated with depression, WMH or brain volume. CONCLUSION: Long-term HNC survivors showed worse cognitive functioning 7 years after treatment. Cognitive function was associated with subjective complaints and fatigue, but not with depressive symptoms. Cerebral infarctions on MRI were correlated with cognitive function, whereas WMH, and brain volume were not.

Progression of carotid intima media thickness after radiotherapy: a long-term prospective cohort study.

BACKGROUND AND PURPOSE: Carotid artery vasculopathy is a long-term complication of radiotherapy (RT) of the neck. We investigated the change in carotid intima media thickness (IMT) and the incidence of ischemic stroke in the first 7 years after radiotherapy (RT) of the neck. MATERIALS AND METHODS: A multicentre prospective cohort study among patients treated for Head and Neck Cancer (HNC) assessed carotid IMT at baseline (before RT) and after a median of 7 years follow-up. We also screened for cerebrovascular risk factors and events. RESULTS: 48 patients underwent IMT measurement at baseline and follow-up (median age 61 years, range 29-87). Mean IMT of the irradiated common carotid arteries was 0.64mm at baseline and 0.74mm at follow-up (p=0.002). Mean delta IMT in the irradiated and non-irradiated common carotid arteries were 0.11 and 0.02mm (p=0.03). Incidence rate of stroke in our cohort, compared to the Dutch population was 8.9 versus 1.5 per 1.000 person years. CONCLUSIONS: IMT in irradiated carotid arteries was significantly increased in the first 7years after RT. The incidence rate of stroke was six fold increased. Patients treated with RT for HNC have sustained risk for developing atherosclerosis of the carotid arteries and future stroke.

Prospective cohort study of carotid intima-media thickness after irradiation.

BACKGROUND: Carotid artery vasculopathy is a potential long-term complication after radiotherapy (RT) of the neck, resulting in cerebrovascular events. The underlying pathophysiology is not well understood and early markers are lacking. We aimed to study whether RT of the neck is associated with increase in carotid intima-media thickness (IMT) and stroke in the first 2 years after RT in patients with head and neck cancer (HNC). METHODS: In this prospective cohort study patients treated with RT of the neck were assessed for measurement of IMT before and 2 years after RT. Endpoints were changed in IMT and incidence of first-ever stroke. RESULTS: Between 2003 and 2008 we included 69 patients (median age, 57 years [25%-75% quartile, 51-64 years], median dose of RT 66 Gy [interquartile range, 60-70]) with baseline and follow-up measurement of IMT. Median IMT at baseline and follow-up was .60 and .62 mm (ratio of geometric means 1.01; 95% confidence interval, .96-1.08; P = .63). Four of 69 patients suffered from a stroke. Mean interval from RT to stroke was 6.8 months. CONCLUSIONS: Our study showed no increase of carotid IMT in the first 2 years after RT of the neck in patients treated for HNC. This indicates that the IMT is not a reliable early marker for postirradiation vasculopathy. However, a high rate of strokes was observed. A longer follow-up period is needed to find the starting point of RT-induced vascular changes.

Clinical characteristics and outcome of intracerebral hemorrhage in young adults.

Data on determinants of prognosis after intracerebral hemorrhage (ICH) in young adults are scarce. Our aim was to identify clinical determinants of prognosis after ICH in adults aged 18-50. We investigated 98 consecutive patients with an ICH, aged 18-50 years, admitted to our hospital between 1980 and 2010. Collected ICH characteristics included presenting symptoms, etiology, location, severity and Glasgow Coma Scale (GCS). Outcomes were case-fatality (death within 30 days), poor functional outcome (modified Rankin Scale >2), long-term mortality and recurrent ICH. We assessed discriminatory power of factors associated with case-fatality [area under receiver operating curve (AUC)]. Case-fatality was 20.4 % (n = 20) and well predicted by the GCS (AUC 0.83). Among 30-day survivors, a poor functional outcome at discharge was present in 51.3 %. During a mean follow-up of 11.3 years mortality was only increased in patients aged 40-50 years [standardized mortality ratio 4.8 (95 % CI 2.3-8.6)], but not in patients aged 18-40 years. Recurrent ICH occurred in 6 patients [10-year cumulative incidence 12.2 % (95 % CI 1.5-22.9 %)], all with the index ICH attributable to structural vascular malformations. Prognosis after ICH in young adults is poor, mainly due to high case-fatality, that is well predicted by the GCS. An exception is 30-day survivors <40 years, who have a similar risk of dying as the general population. Recurrence risk is especially present in patients with structural vascular malformations, whereas risk seems to be very low in other patients.

Long term cerebral and vascular complications after irradiation of the neck in head and neck cancer patients: a prospective cohort study: study rationale and protocol.

BACKGROUND: Successful treatment options for cancer result in more young long-term survivors prone for long-term complications. Carotid artery vasculopathy is a potential long-term complication after radiotherapy of the neck, resulting in cerebrovascular events and probably deficits in cognitive and motor functioning. Better insight into the underlying pathofysiology of radiotherapy induced carotid artery vasculopathy is needed for prognostic purposes and to develop preventive strategies. METHODS/DESIGN: The current study is a prospective cohort study on the long-term cerebral and vascular complications after radiotherapy of the neck, in 103 patients treated for head and neck cancer, included in our study database between 2002 and 2008. Baseline protocol (before radiotherapy) included screening for cerebrovascular risk factors and intima media thickness measurement of carotid arteries by ultrasonography. Follow-up assessment more than 5 years after radiotherapy included screening of cerebrovascular risk factors, cerebrovascular events, neurological examination with gait and balance tests, extensive neuropsychological examination, self-report questionnaires, ultrasonography of the carotid arteries with measurement of intima media thickness and elastography, magnetic resonance imaging of the brain and magnetic resonance angiography of the carotid arteries. DISCUSSION: The current study adds to the understanding of the causes and consequences of long-term cerebral and vascular changes after radiotherapy of the neck. These data will be helpful to develop a protocol for diagnostic and preventive strategies for long-term neurological complications in future head and neck cancer patients with anticipated radiotherapy treatment.