Erik Hessen

Consequences of antiepileptic drug withdrawal : A randomized, double-blind study (Akershus Study)

Objective: Despite side effects associated with the use of antiepileptic drugs (AEDs), withdrawal of AEDs remains controversial, even after prolonged seizure freedom. The main objective of this study was to assess the effects of AED withdrawal on cognitive functions, seizure relapse, health‐related quality of life (HRQOL), and EEG results. Additionally, potential predictors for freedom from seizures after AED withdrawal were studied.

Neuropsychological function 23 years after mild traumatic brain injury: A comparison of outcome after paediatric and adult head injuries

Primary objective: To the authors’ knowledge no study comparing very long-term neuropsychological outcome after mild paediatric and adult traumatic brain injury (TBI) has been published. The primary objective of this study was to compare neuropsychological outcome 23 years after mainly mild paediatric and adult TBI. Research design: The study was a neuropsychological follow-up 23 years after a prospective head injury study conducted at a Norwegian public hospital. Methods and procedures: One hundred and nineteen patients were assessed with a comprehensive neuropsychological test battery. Of these, 45 were paediatric TBI and 74 were adult TBI. Main outcomes and results: Both the paediatric and adult groups obtained scores in the normal range. In the paediatric group significant relationships were found between head injury severity and current neuropsychological function. The most important predictors of poor outcome were length of post-traumatic amnesia (PTA) and a combination of PTA and EEG pathology within 24 hours of injury. No influence of pre- and post-injury risk factors on current neuropsychological function was evident. Conclusions: The findings indicate that children sustaining complicated mild TBI may be more vulnerable to development of chronic mild neuropsychological dysfunction than adults sustaining similar head injuries.

Influence of Major Antiepileptic Drugs on Attention, Reaction Time, and Speed of Information Processing: Results from a Randomized, Double-blind, Placebo-controlled Withdrawal Study of Seizure-free Epilepsy Patients Receiving Monotherapy

Summary:  Purpose: All major antiepileptic drugs (AEDs) have been reported to be associated with cognitive side effects. Uncertainty exists regarding the degree of cognitive effects, primarily because many studies do not adhere to basic standards of methodology and design. The aim of this study was to assess the effect of discontinuation of AEDs in patients receiving monotherapy on measures of attention, reaction time, and speed of information processing.

Diffusion Tensor Imaging Surpasses Cerebrospinal Fluid as Predictor of Cognitive Decline and Medial Temporal Lobe Atrophy in Subjective Cognitive Impairment and Mild Cognitive Impairment

Neuropathological correlates of Alzheimers disease (AD) emerge years before dementia. Biomarkers preceding cognitive decline and reflecting the causative processes can potentially aid early intervention and diagnosis. Diffusion tensor imaging (DTI) indirectly reflects tissue microstructure. To answer whether DTI is an early biomarker for AD and to explore the relationship between DTI and the established biomarkers of medial temporal lobe atrophy and cerebrospinal fluid (CSF) Aβ(42), T-tau, and P-tau, we longitudinally studied normal controls and patients with subjective (SCI) or mild (MCI) cognitive impairment. 21 controls and 64 SCI or MCI cases recruited from a university-hospital based memory clinic were re-examined after two to three years. FreeSurfer was used for longitudinal processing of morphometric data, and DTI derived fractional anisotropy, radial diffusivity, and mean diffusivity were analyzed in Tract-Based Spatial Statistics. Using regression models, we explored and compared the predictive powers of DTI and CSF biomarkers in regard to cognitive change and atrophy of the medial temporal lobe. Both DTI and CSF biomarkers significantly predicted cognitive decline and atrophy in the medial temporal lobe. In this population, however, DTI was a better predictor of dementia and AD-specific medial temporal lobe atrophy than the CSF biomarkers. The case for DTI as an early biomarker for AD is strengthened, but further studies are needed to confirm these results.

Executive Dysfunction in Mild Cognitive Impairment is Associated with Changes in Frontal and Cingulate White Matter Tracts

Mild cognitive impairment (MCI) may affect multiple neuropsychological domains. While amnestic MCI is associated with Alzheimers disease, patterns of brain pathology in non-amnestic subtypes have been less studied. Twenty-three patients with attention/executive MCI (a/e MCI), seen at a university-based memory clinic, and 23 normal controls, matched according to age, gender, and education, were included in this study. All subjects were assessed with a neuropsychological test battery, including tests of memory, attention and executive function, and underwent magnetic resonance imaging. Diffusion tensor imaging derived white matter (WM) tract radial and mean diffusivity (DR and MD) were assessed using Tract-Based Spatial Statistics, and cortical thickness (CTH) was assessed using FreeSurfer. This study investigated changes of WM DR/MD and CTH in subjects with a/e MCI, and associations between these changes and different a/e subfunctions. WM DR/MD underlying rostral middle frontal, medial orbitofrontal, caudal anterior cingulate, posterior cingulate, retrosplenial and entorhinal cortices was higher for the a/e MCI than the control group, but CTH was not different from controls in any of the regions. WM DR/MD underlying superior frontal, rostral middle frontal, lateral/medial orbitofrontal and retrosplenial cortices were significantly associated with inhibition/switching performance, while caudal middle frontal CTH was significantly associated with attention and divided attention in the patient group. We conclude that increased WM DR/MD in frontal and cingulate regions and cortical thinning in caudal middle frontal region are both associated with executive dysfunction in MCI.

Amyloid-β and α-synuclein cerebrospinal fluid biomarkers and cognition in early Parkinson's disease

INTRODUCTION Cognitive impairment in early Parkinsons disease (PD) is common and distinct from early Alzheimers disease. Predictors and mechanisms are only partially known, but α-synuclein, amyloid-β and tau dysmetabolism may be involved. Our aim was to study associations between cerebrospinal fluid biomarkers (CSF) and cognition in non-dementia PD compared to normal controls (NC) and non-PD patients with mild cognitive impairment (MCI non-PD). METHODS Patients were classified as having normal, subjective or mild cognitive impairment after cognitive screening. CSF levels of total α-synuclein (t-α-syn), amyloid-β (Aβ) 38, 40 and 42, total tau (T-tau) and phosphorylated tau (P-tau) were measured in 34 NC, 31 early, non-dementia PD and 28 MCI non-PD patients. A well validated neuropsychological test battery was administered. RESULTS In the PD group, 13 had normal cognition, 4 had subjective and 14 mild cognitive impairment. PD patients had significantly lower CSF biomarker levels of t-α-syn, Aβ38, 40 and 42, T-tau and P-tau compared to NC. Compared to MCI non-PD, t-α-syn, Aβ38 and 40, T-tau and P-tau were also lower, while Aβ42 was significantly higher in the PD group. Aβ38 and 40 correlated strongly with t-α-syn levels in PD. Lower Aβ42 was associated with decreased verbal learning, delayed verbal recall and response inhibition in PD. CONCLUSION While Aβ38, 40 and t-α-syn levels are strongly correlated, only lower Aβ42 was associated with reduced cognitive functions in early PD, mainly connected to medial temporal lobe-based cognitive functions.

Correlates of Subjective and Mild Cognitive Impairment: Depressive Symptoms and CSF Biomarkers

Aims: To improve early diagnosis of dementia disease, this study investigates correlates of cognitive complaints and cognitive test performance in patients with subjective (SCI) and mild (MCI) cognitive impairment. Methods: Seventy patients from a memory clinic, aged 45-79, with a score of 2 (n = 23) or 3 (n = 47) on the Global Deterioration Scale, were included. CSF biomarkers [Aβ42, total tau (T-tau) and phosphorylated tau (P-tau)], depressive symptoms, cognitive performance, and complaints were examined. Results: Correlation analysis showed that cognitive complaints increased with decreasing cognitive performance in SCI and decreased with decreasing performance in MCI. Linear regression models revealed that cognitive complaints were associated with depressive symptoms in both groups of patients, while cognitive performance was associated with CSF Aβ42 and P-tau in SCI and with T-tau and P-tau in MCI. Conclusion: These results suggest that depressive symptoms are associated with cognitive complaints, while degenerative changes are associated with objective cognitive decline in high-risk predementia states.

Diaschisis after thalamic stroke: a comparison of metabolic and structural changes in a patient with amnesic syndrome.

Introduction–  We present a patient with a left anteromedial thalamic lesion with an amnesic syndrome. The patient underwent neuropsychological testing, cerebrospinal fluid (CSF) analyses, magnetic resonance imaging (MRI) [T2, flair, and diffusion tensor imaging (DTI)] and [18F]‐2‐fluoro‐deoxy‐d‐glucose positron emission tomography (FDG‐PET) to assess indirect effects of thalamic lesions on cortical function.

Indicators of complicated mild TBI predict MMPI-2 scores after 23 years

Primary objective: Research suggests that post-concussive syndrome may become persistent after mild traumatic brain injury (mTBI). The aim of this study was to investigate determinants of subjective complaints, characteristic for post-concussive syndrome, 23 years after mTBI. Research design: The study was a follow-up after a prospective head injury study at a general hospital in Norway. Methods and procedures: Ninety-seven patients were assessed with the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) 23 years after sustaining primarily mTBI. Main outcomes and results: A good overall outcome was found with scores close to the normative mean, average length of education and normal employment rate. However, the patients that sustained complicated mTBI showed somewhat more pathological scores, well-matched with mild post-concussive syndrome. The most important predictors of poor outcome were a combination of post-traumatic amnesia >30 minutes and EEG pathology within 24 hours after TBI. No influence of pre- and post-injury risk factors on current MMPI-2 profiles was found. Conclusions: The results are in line with previous research findings and support the notion of potentially differential impact of uncomplicated vs. complicated mTBI. The findings suggest that complicated mTBI may cause subtle chronic symptoms typical of post-concussive syndrome.

MMPI-2 profiles 23 years after paediatric mild traumatic brain injury

Primary objective: Research suggest that post-concussive syndrome after mild traumatic brain injury (mTBI) is more common than chronic cognitive impairment. The aim of this study was to investigate very long-term outcome of subjective complaints after paediatric mTBI. Research design: The study was a follow-up 23 years after a prospective head injury study at a general hospital in Norway. Methods and procedures: Forty-one patients were assessed with the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) 23 years after sustaining mTBI as children. Main outcomes and results: A good overall outcome was found with scores close to the normative mean, average length of education and normal employment rate. However, the children that sustained complicated mTBI showed slightly more pathological scores, typical for mild post-concussive syndrome. The most important predictors of poor outcome were skull fracture and a combination of post-traumatic amnesia > 30 minutes and EEG pathology within 24 hours after TBI. No influence of pre- and post-injury risk factors on current MMPI-2 profiles was evident. Conclusions: The results give support for the notion of potentially differential impact of uncomplicated vs complicated mTBI. The findings suggest that children and adolescents sustaining complicated mTBI may be at risk of developing subtle chronic symptoms typical of post-concussive syndrome.