Niklas Lenfeldt

Transcranial Doppler pulsatility index: not an accurate method to assess intracranial pressure.

BACKGROUNDTranscranial Doppler sonography (TCD) assessment of intracranial blood flow velocity has been suggested to accurately determine intracranial pressure (ICP). OBJECTIVEWe attempted to validate this method in patients with communicating cerebrospinal fluid systems using predetermined pressure levels. METHODSTen patients underwent a lumbar infusion test, applying 4 to 5 preset ICP levels. On each level, the pulsatility index (PI) in the middle cerebral artery was determined by measuring the blood flow velocity using TCD. ICP was simultaneously measured with an intraparenchymal sensor. ICP and PI were compared using correlation analysis. For further understanding of the ICP-PI relationship, a mathematical model of the intracranial dynamics was simulated using a computer. RESULTSThe ICP-PI regression equation was based on data from 8 patients. For 2 patients, no audible Doppler signal was obtained. The equation was ICP = 23*PI + 14 (R2 = 0.22, P < .01, N = 35). The 95% confidence interval for a mean ICP of 20 mm Hg was −3.8 to 43.8 mm Hg. Individually, the regression coefficients varied from 42 to 90 and the offsets from −32 to +3. The mathematical simulations suggest that variations in vessel compliance, autoregulation, and arterial pressure have a serious effect on the ICP-PI relationship. CONCLUSIONSThe in vivo results show that PI is not a reliable predictor of ICP. Mathematical simulations indicate that this is caused by variations in physiological parameters.

Idiopathic normal pressure hydrocephalus: increased supplementary motor activity accounts for improvement after CSF drainage.

In patients with idiopathic normal pressure hydrocephalus (INPH), the changes in brain function that take place in conjunction with improved behavioural performance after CSF drainage is still unknown. In this study, we use functional MRI (fMRI) to investigate the changes in cortical activity that accompany improved motor and cognitive performance after long-term external lumbar drainage (ELD) of CSF in patients with INPH. Eighteen INPH patients were initially included together with age- and sex-matched controls. Data from 11 INPH patients were analysed both before and after ELD. The average drain volume for these 11 patients was 400 ml/3 days. Brain activation was investigated by fMRI before and after the procedure on a 1.5T Philips scanner using protocols taxing motor performance (finger tapping and reaction time) and cognitive functioning (memory and attention). Behavioural data were compared using non-parametric tests at a significance level of 0.05, whereas fMRI data were analysed by statistical parametric mapping including conjunction analysis of areas with enhanced activity after drainage in patients and areas activated in controls (P < 0.005, uncorrected). Improved regions were defined as areas in the INPH brain that increased in activity after ELD with the requirement that the same areas were activated in control subjects. Following ELD, right-hand finger tapping improved from 104 +/- 38 to 117 +/- 25 (mean +/- SD) (P = 0.02). Left-hand finger tapping showed a tendency to improve, the number of keystrokes increasing from 91 +/- 40 to 105 +/- 20 (P = 0.12). Right-hand reaction time improved from 1630 +/- 566 ms to 1409 +/- 442 ms, whereas left-hand reaction time improved from 1760 +/- 600 ms to 1467 +/- 420 ms (both P-values = 0.01). Significant improvements in motor performance were accompanied by bilateral increased activation in the supplementary motor area. No improvement was found in cognitive functioning. The results suggest that motor function recovery in INPH patients after CSF removal is related to enhanced activity in medial parts of frontal motor areas considered crucial for motor planning; a finding consistent with INPH being a syndrome related to a reversible suppression of frontal periventricular cortico-basal ganglia-thalamo-cortical pathways.

Diffusion tensor imaging reveals supplementary lesions to frontal white matter in idiopathic normal pressure hydrocephalus.

BACKGROUND:Idiopathic normal-pressure hydrocephalus (INPH) is associated with white matter lesions, but the extent and severity of the lesions do not cohere with symptoms or improvement after shunting, implying the presence of further, yet undisclosed, injuries to white matter in INPH. OBJECTIVE:To apply diffusion tensor imaging (DTI) to explore white matter lesions in patients with INPH before and after drainage of cerebrospinal fluid (CSF). METHODS:Eighteen patients and 10 controls were included. DTI was performed in a 1.5T MRI scanner before and after 3-day drainage of 400 mL of CSF. Regions of interest included corpus callosum, capsula interna, frontal and lateral periventricular white matter, and centrum semiovale. White matter integrity was quantified by assessing fractional anisotropies (FA) and apparent diffusion coefficients (ADC), comparing them between patients and controls and between patients before and after drainage. The significance level corresponded to .05 (Bonferroni corrected). RESULTS:Decreased FA in patients was found in 3 regions (P < .002, P < .001, and P < .001) in anterior frontal white matter, whereas elevated ADC was found in genu corpus callosum (P < .001) and areas of centrum semiovale associated with the precentral gyri (P < .002). Diffusion patterns in these areas did not change after drainage. CONCLUSION:DTI reveals subtle injuries—interpreted as axonal loss and gliosis—to anterior frontal white matter where high-order motor systems between frontal cortex and basal ganglia travel, further supporting the notion that motor symptoms in INPH are caused by a chronic ischemia to the neuronal systems involved in the planning processes of movements.

Fractional anisotropy in the substantia nigra in Parkinson's disease: a complex picture.

This study employs magnetic resonance imaging (MRI) diffusion tensor imaging to compare diffusion measures in the brains of patients with Parkinsons disease (PD) with healthy controls using longitudinal data.

Three-day CSF drainage barely reduces ventricular size in normal pressure hydrocephalus

Objective: External lumbar drainage (ELD) of CSF is a test to determine the suitability of a shunt for patients with normal pressure hydrocephalus (NPH), but its effect on ventricular volume is not known. This study investigates the effect of 3-day ELD of 500 mL on ventricular size and clinical features in patients with idiopathic NPH. Methods: Fifteen patients were investigated in a 1.5-T MRI scanner before and after ELD. Ventricular volume was measured manually. Clinical features involved motor and cognitive functions, testing primarily gait and attention. Reduction in ventricular volume was correlated to total drain volume and clinical parameters. Statistical tests were nonparametric, and p < 0.05 was required for significance. Results: Drain volume was 415 mL (median 470 mL, range 160–510 mL). Ventricular size was reduced in all patients, averaging 3.7 mL (SD 2.2 mL, p < 0.001), which corresponded to a 4.2% contraction. The ratio of volume contraction to drain volume was only 0.9%. Seven patients improved in gait and 6 in attention. Ventricular reduction and total drain volume correlated neither with improvement nor with each other. The 7 patients with the largest drain volumes (close to 500 mL), had ventricular changes varying from 1.3 to 7.5 mL. Conclusions: Clinical improvement occurs in patients with NPH after ELD despite unaltered ventricles, suggesting that ventricular size is of little relevance for postshunt improvement or determining shunt function. The clinical effect provided by ELD, mimicking shunting, is probably related to the recurring CSF extractions rather than to the cumulative effect of the drainage on ventricular volume.

Intracranial Pressure and Pulsatility Index

Idiopathic Normal Pressure Hydrocephalus (INPH) is a condition affecting gait, cognition and continence. Radiological examination reveals enlarged ventricles of the brain. A shunt that drains CSF from the ventricles to the abdomen often improves the symptoms. Much research on INPH has been focused on identifying tests that predict the outcome after shunt surgery. As part of this quest, there are attempts to find measurement methods of intracranial parameters that are valid, reliable, tolerable and safe for patients.Todays technologies for intracranial pressure (ICP) measurement are invasive, often requiring a burr-hole in the skull. Recently, a method for non-invasive ICP measurements was suggested: the Pulsatile Index (PI) calculated from transcranial Doppler data assessed from the middle cerebral artery. In this thesis the relation between PI and ICP was explored in INPH patients during controlled ICP regulation by lumbar infusion. The confidence interval for predicted ICP, based on measured PI was too large for the method to be of clinical utility.In the quest for better predictive tests for shunt success in INPH, recent studies have shown promising results with criteria based on cardiac related ICP wave amplitudes. The brain ventricular system, and the fluid surrounding the spinal cord are in contact. In this thesis it was shown that ICP waves could be measured via lumbar subarachnoid space, with a slight underestimation.One of the cardinal symptoms of hydrocephalus is cognitive impairment. Neuropsychological studies have demonstrated cognitive tests that are impaired and improve after shunt surgery in INPH patients. However, there is currently no standardized test battery and different studies use different tests. In response, in this thesis a fully automated computerized neuropsychological test battery was developed. The validity, reliability, responsiveness to improvement after shunt surgery and feasibility for testing INPH patients was demonstrated. It was also demonstrated that INPH patients were impaired in all subtests, compared to healthy elderly.

Frontal white matter injuries predestine gait difficulties in Parkinson's disease

This study applies diffusion tensor imaging (DTI) to determine differences in neuronal integrity between motor phenotypes in Parkinsons disease.

Are intracranial pressure wave amplitudes measurable through lumbar puncture

The aim of this study was to investigate whether pulsations measured in the brain correspond to those measured in lumbar space, and subsequently whether lumbar punctures could replace invasive recordings.

Diffusion measures in early stage parkinsonism: Controversial findings including hemispheric lateralisation

Diffusion measures in early stage parkinsonism : controversial findings including hemispheric lateralisation

Alterations in white matter microstructure are associated with goal-directed upper-limb movement segmentation in children born extremely preterm

Altered white matter microstructure is commonly found in children born preterm (PT), especially those born at an extremely low gestational age (GA). These children also commonly show disturbed motor function. This study explores the relation between white matter alterations and upper‐limb movement segmentation in 41 children born PT (19 girls), and 41 children born at term (18 girls) at 8 years. The PT group was subdivided into extremely PT (E‐PT; GA = 25–27 weeks, N = 10), very PT (V‐PT; GA = 28–32 weeks, N = 13), and moderately PT (M‐PT; GA = 33–35 weeks, N = 18). Arm/hand preference (preferred/non‐preferred) was determined through object interactions and the brain hemispheres were designated accordingly. White matter alterations were assessed using diffusion tensor imaging in nine areas, and movement segmentation of the body‐parts head, shoulder, elbow, and wrist were registered during a unimanual goal‐directed task. Increased movement segmentation was demonstrated consistently on the preferred side in the E‐PT group compared with the term born group. Also compared with the term born peers, the E‐PT group demonstrated reduced fractional anisotropy (FA) in the cerebral peduncle (targeting the corticospinal tract) in the hemisphere on the non‐preferred side and in the splenium of corpus callosum. In contrast, in the anterior internal capsule on the preferred side, the E‐PT group had increased FA. Lower FA in the cerebral peduncle, but higher FA in the anterior internal capsule, was associated with increased movement segmentation across body‐parts in a contralateral manner. The results suggest that impaired development of sensorimotor tracts in E‐PT children could explain a sub‐optimal spatiotemporal organization of upper‐limb movements. Hum Brain Mapp 38:5051–5068, 2017.