Peter Jan van Laar

A novel diagnostic approach to patients with myoclonus

Myoclonus is a hyperkinetic movement disorder characterized by brief, involuntary muscular jerks. Recognition of myoclonus and determination of the underlying aetiology remains challenging given that both acquired and genetically determined disorders have varied manifestations. The diagnostic work-up in myoclonus is often time-consuming and costly, and a definitive diagnosis is reached in only a minority of patients. On the basis of a systematic literature review up to June 2015, we propose a novel diagnostic eight-step algorithm to help clinicians accurately, efficiently and cost-effectively diagnose myoclonus. The large number of genes implicated in myoclonus and the wide clinical variation of these genetic disorders emphasize the need for novel diagnostic techniques. Therefore, and for the first time, we incorporate next-generation sequencing (NGS) in a diagnostic algorithm for myoclonus. The initial step of the algorithm is to confirm whether the movement disorder phenotype is consistent with, myoclonus, and to define its anatomical subtype. The next steps are aimed at identification of both treatable acquired causes and those genetic causes of myoclonus that require a diagnostic approach other than NGS. Finally, other genetic diseases that could cause myoclonus can be investigated simultaneously by NGS techniques. To facilitate NGS diagnostics, we provide a comprehensive list of genes associated with myoclonus.

FDG-PET for Prediction of AD Dementia in Mild Cognitive Impairment. A Review of the State of the Art with Particular Emphasis on the Comparison with Other Neuroimaging modalities (MRI and Perfusion SPECT).

This review article aims at providing a state-of-the-art review of the role of fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging (FDG-PET) in the prediction of Alzheimers dementia in subjects suffering mild cognitive impairment (MCI), with a particular focus on the predictive power of FDG-PET compared to structural magnetic resonance imaging (sMRI). We also address perfusion single photon emission computed tomography (SPECT) as a less costly and more accessible alternative to FDG-PET. A search in PubMed was performed, taking into consideration relevant scientific articles published in English within the last five years and limited to human studies. This recent literature confirms the effectiveness of FDG-PET and sMRI for prediction of AD dementia in MCI. However, there are discordant results regarding which image modality is superior. This could be explained by the high variability of metrics used to evaluate both imaging modalities and/or by sampling/population issues such as age, disease severity and conversion time. FDG-PET seems to outperform sMRI in rapidly converting early-onset MCI individuals, whereas sMRI may outperform FDG-PET in late-onset MCI subjects, in which case FDG PET might only provide a complementary role. Although FDG-PET performs better than perfusion SPECT, current evidence confirms perfusion SPECT as a valid alternative when FDG- PET is not available. Finally, possible future directions in the field are discussed.

Dynamics of cerebral blood flow in patients with mild non-ischaemic heart failure.

Heart failure (HF) is associated with tissue hypoperfusion and congestion leading to organ dysfunction. Although cerebral blood flow (CBF) is preserved over a wide range of perfusion pressures in healthy subjects, it is impaired in end‐stage HF. We aimed to compare CBF, autoregulation, and cognitive function in patients with mild non‐ischaemic HF with healthy controls.

Hemodialysis Induces an Acute Decline in Cerebral Blood Flow in Elderly Patients

The initiation of hemodialysis is associated with an accelerated decline of cognitive function and an increased incidence of cerebrovascular accidents and white matter lesions. Investigators have hypothesized that the repetitive circulatory stress of hemodialysis induces ischemic cerebral injury, but the mechanism is unclear. We studied the acute effect of conventional hemodialysis on cerebral blood flow (CBF), measured by [15O]H2O positron emission tomography-computed tomography (PET-CT). During a single hemodialysis session, three [15O]H2O PET-CT scans were performed: before, early after the start of, and at the end of hemodialysis. We used linear mixed models to study global and regional CBF change during hemodialysis. Twelve patients aged ≥65 years (five women, seven men), with a median dialysis vintage of 46 months, completed the study. Mean (±SD) arterial BP declined from 101±11 mm Hg before hemodialysis to 93±17 mm Hg at the end of hemodialysis. From before the start to the end of hemodialysis, global CBF declined significantly by 10%±15%, from a mean of 34.5 to 30.5 ml/100g per minute (difference, -4.1 ml/100 g per minute; 95% confidence interval, -7.3 to -0.9 ml/100 g per minute; P=0.03). CBF decline (20%) was symptomatic in one patient. Regional CBF declined in all volumes of interest, including the frontal, parietal, temporal, and occipital lobes; cerebellum; and thalamus. Higher tympanic temperature, ultrafiltration volume, ultrafiltration rate, and pH significantly associated with lower CBF. Thus, conventional hemodialysis induces a significant reduction in global and regional CBF in elderly patients. Repetitive intradialytic decreases in CBF may be one mechanism by which hemodialysis induces cerebral ischemic injury.

Diagnostic accuracy of magnetic resonance imaging techniques for treatment response evaluation in patients with head and neck tumors, a systematic review and meta-analysis

Background Novel advanced MRI techniques are investigated in patients treated for head and neck tumors as conventional anatomical MRI is unreliable to differentiate tumor from treatment related imaging changes. Purpose As the diagnostic accuracy of MRI techniques to detect tumor residual or recurrence during or after treatment is variable reported in the literature, we performed a systematic meta-analysis. Data sources Pubmed, EMBASE and Web of Science were searched from their first record to September 23th 2014. Study selection Studies reporting diagnostic accuracy of anatomical, ADC, perfusion or spectroscopy to identify tumor response confirmed by histology or follow-up in treated patients for head and neck tumors were selected by two authors independently. Data analysis Two authors independently performed data extraction including true positives, false positives, true negatives, false negatives and general study characteristics. Meta-analysis was performed using bivariate random effect models when ≥5 studies per test were included. Data synthesis We identified 16 relevant studies with anatomical MRI and ADC. No perfusion or spectroscopy studies were identified. Pooled analysis of anatomical MRI of the primary site (11 studies, N = 854) displayed a sensitivity of 84% (95%CI 72–92) and specificity of 82% (71–89). ADC of the primary site (6 studies, N = 287) showed a pooled sensitivity of 89% (74–96) and specificity of 86% (69–94). Limitations Main limitation are the low, but comparable quality of the included studies and the variability between the studies. Conclusions The higher diagnostic accuracy of ADC values over anatomical MRI for the primary tumor location emphases the relevance to include DWI with ADC for response evaluation of treated head and neck tumor patients.

Diagnostic accuracy of magnetic resonance imaging techniques for treatment response evaluation in patients with high-grade glioma, a systematic review and meta-analysis

ObjectiveTreatment response assessment in high-grade gliomas uses contrast enhanced T1-weighted MRI, but is unreliable. Novel advanced MRI techniques have been studied, but the accuracy is not well known. Therefore, we performed a systematic meta-analysis to assess the diagnostic accuracy of anatomical and advanced MRI for treatment response in high-grade gliomas.MethodsDatabases were searched systematically. Study selection and data extraction were done by two authors independently. Meta-analysis was performed using a bivariate random effects model when ≥5 studies were included.ResultsAnatomical MRI (five studies, 166 patients) showed a pooled sensitivity and specificity of 68% (95%CI 51–81) and 77% (45–93), respectively. Pooled apparent diffusion coefficients (seven studies, 204 patients) demonstrated a sensitivity of 71% (60–80) and specificity of 87% (77–93). DSC-perfusion (18 studies, 708 patients) sensitivity was 87% (82–91) with a specificity of 86% (77–91). DCE-perfusion (five studies, 207 patients) sensitivity was 92% (73–98) and specificity was 85% (76–92). The sensitivity of spectroscopy (nine studies, 203 patients) was 91% (79–97) and specificity was 95% (65–99).ConclusionAdvanced techniques showed higher diagnostic accuracy than anatomical MRI, the highest for spectroscopy, supporting the use in treatment response assessment in high-grade gliomas.Key points• Treatment response assessment in high-grade gliomas with anatomical MRI is unreliable• Novel advanced MRI techniques have been studied, but diagnostic accuracy is unknown• Meta-analysis demonstrates that advanced MRI showed higher diagnostic accuracy than anatomical MRI• Highest diagnostic accuracy for spectroscopy and perfusion MRI• Supports the incorporation of advanced MRI in high-grade glioma treatment response assessment

Surgical Accuracy of 3-Tesla Versus 7-Tesla Magnetic Resonance Imaging in Deep Brain Stimulation for Parkinson Disease

BACKGROUND In deep brain stimulation (DBS), accurate placement of the lead is critical. Target definition is highly dependent on visual recognition on magnetic resonance imaging (MRI). We prospectively investigated whether the 7-T MRI enabled better visualization of targets and led to better placement of leads compared with the 1.5-T and the 3-T MRI. METHODS Three patients with PD (mean, 55 years) were scanned on 1.5-, 3-, and 7-T MRI before surgery. Tissue contrast and signal-to-noise ratio were measured. Target coordinates were noted on MRI and during surgery. Differences were analyzed with post-hoc analysis of variance. RESULTS The 7-T MRI demonstrated a significant improvement in tissue visualization (P < 0.005) and signal-to-noise ratio (P < 0.005). However, no difference in the target coordinates was found between the 7-T and the 3-T MRI. CONCLUSIONS Although the 7-T MRI enables a significant better visualization of the DBS target in patients with PD, we found no clinical benefit for the placement of the DBS leads.

Functional MRI for Treatment Evaluation in Patients with Head and Neck Squamous Cell Carcinoma : A Review of the Literature from a Radiologist Perspective

Purpose of reviewTo show the role of functional MRI in patients treated for head and neck squamous cell carcinoma.Recent findingsMRI is commonly used for treatment evaluation in patients with head and neck tumors. However, anatomical MRI has its limits in differentiating between post-treatment effects and tumor recurrence. Recent studies showed promising results of functional MRI for response evaluation.SummaryThis review analyzes possibilities and limitations of functional MRI sequences separately to obtain insight in the post-therapy setting. Diffusion, perfusion and spectroscopy show promise, especially when utilized complimentary to each other. These functional MRI sequences aid in the early detection which might improve survival by increasing effectiveness of salvage therapy. Future multicenter longitudinal prospective studies are needed to provide standardized guidelines for the use of functional MRI in daily clinical practice.

The relation between flocculus volume and tinnitus after cerebellopontine angle tumor surgery

Purpose: Chronic tinnitus is a common symptom after cerebellopontine angle (CPA) tumor removal. Sometimes, the tinnitus is gaze‐modulated. In that case, patients can change the loudness or pitch of their tinnitus by ocular movements. During tumor removal by a retrosigmoid craniotomy, the cerebellar flocculus is manipulated by the surgical approach to access the tumor. The flocculus has been associated with tinnitus in rats, and is involved in eye‐gaze control. This suggests that the flocculus may have a role in gaze‐modulated tinnitus after CPA tumor removal. In order to investigate this hypothesis, the relation between the flocculus volume and the characteristics of postoperative tinnitus was studied. Results: A single‐center cohort of 51 patients completed a questionnaire after CPA tumor removal. The questionnaire asked for the effect of eye movements on tinnitus and included the Tinnitus Functional Index (TFI). Tinnitus was present in 36 patients (71% of 51), of which 29 (81% of 36) described gaze‐modulation. The median TFI was 22 (range 0–85). A postoperative MRI‐scan of sufficient quality was available in 34 cases. The volumes of the (para)flocculi ipsilateral and contralateral to the surgery, and the ratio of these volumes were similar between patients with and without tinnitus. The TFI correlated with the volume of both ipsi‐ and contralateral (para)flocculus (rs(23) = .516, p = .008 and rs(23) = .430, p = .032). The ipsilateral‐to‐contralateral volume ratio of the (para)flocculi volumes was significantly lower in patients that could modulate the loudness of their tinnitus by eye gaze, compared to patients that could not (t(23) = 3.337, p = .003). Conclusions: The lack of a relation between flocculus volumes and the presence of tinnitus, combined with the significant correlation between tinnitus severity and flocculus volumes, suggests that the flocculus may not be the primary source of tinnitus, but is likely to mediate tinnitus severity. The reduced ipsi‐to‐contralateral volume ratio in patients with gaze‐modulated tinnitus suggests that atrophy of the flocculus on the surgery side triggers cross‐modal interactions leading to modulation of tinnitus. HighlightsTinnitus and bilateral (para)flocculus volume was determined in patients after unilateral cerebellopontine angle surgery.The ipsi‐to‐contralateral volume ratio was not statistically different between patients with and without tinnitus.The Tinnitus Functional Index (TFI) in patients with tinnitus was correlated with the bilateral flocculus volumes.The ipsi‐to‐contralateral volume ratio was relatively small in patients that could modulate their tinnitus by ocular gaze.These results suggest that the flocculus mediates tinnitus severity and is involved in gaze‐modulated tinnitus.

Social cognition impairments after aneurysmal subarachnoid haemorrhage: Associations with deficits in interpersonal behaviour, apathy, and impaired self-awareness

&NA; Behavioural disturbances are frequently found after aneurysmal subarachnoid haemorrhage (aSAH). Social cognition impairments have been suggested as a possible underlying mechanism for behavioural problems. Also, aSAH is likely to result in damage affecting frontal‐subcortical circuits underlying social cognition. Therefore, we aimed to investigate social cognition after aSAH and its associations with behavioural problems (deficits in interpersonal behaviour, apathy, and impaired self‐awareness) and focal as well as diffuse brain damage. 88 aSAH patients (in the subacute phase post‐aSAH) and 60 age‐, sex‐ and education‐matched healthy controls participated. Tasks for emotion recognition, Theory of Mind (ToM), and empathy as well as questionnaires were used. Cortical infarctions in frontal and non‐frontal areas on MRI, aneurysm circulation and aSAH‐related events were taken into account. Compared to healthy controls, aSAH patients performed significantly worse on tasks for emotion recognition, ToM and empathy. Poor performance on ToM and emotion recognition was associated with proxy‐ratings indicating impaired interpersonal behaviour and apathy and with indications of impaired self‐awareness. No associations were found between deficits in social cognition and frontal or non‐frontal cortical lesions on MRI. Also, aneurysm circulation and aSAH‐related events such as hydrocephalus, vasospasm, and treatment method did not explain why and how social cognitive deficits did occur after aSAH. In conclusion, emotion recognition, ToM and empathy were clearly impaired in aSAH patients and these deficits were related to apathy and deficits in interpersonal behaviour as reported by proxies and to impaired self‐awareness. This association strengthens the assumption of impaired social cognition as an underlying construct of behavioural problems after aSAH. Consequently, social cognition tests and proxy‐ratings should be used in clinical practice, irrespective of lesion location on MRI or aneurysm circulation, to improve the detection and treatment of apathy and deficits in interpersonal behaviour after aSAH. HighlightsAspects of social cognition (emotion recognition, ToM, and empathy) were impaired post‐aSAH.Social cognition deficits were associated to behavioural disturbances after aSAH.An association between impaired self‐awareness and deficits in social cognition was found.Social cognitive deficits were not related to lesion location on MRI or aneurysm circulation.