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BackgroundSporadic Parkinson’s disease (sPD) is an aetiologically heterogeneous disorder. Identification of distinct pathogenic mechanisms causing sPD will be crucial to develop future “Precision Medicine” approaches. 31P-MRS is a non-invasive tool that can quantify key bionenergetic metabolites in individual patients.ObjectiveTo determine whether 31P-MRS can identify mitochondrial dysfunction in the midbrain/sub- stantia nigra of individual PD patients and correlates with trial-relevant clinical aspects of PD.Methods31P-MRS spectra were obtained from 35 sPD patients and 25 healthy, age-matched controls. Spectra were analysed using the jMRUI software package and AMARES spectral fitting algorithm. Clinical assessment included widely utilised clinical rating scales, genetic analysis and the calculation of predicted risk of rapid disease progression.ResultsThere was a significantly broader variance in 31P-MRS midbrain ATP with 1/3 of all PD patients having ATP levels > 2 standard deviations outside the mean control values (p=0.0030). Higher midbrain phosphocreatine was associated with greater risk of rapid disease progression (p= 0.0384).Conclusions31P-MRS may help to identify a subgroup of sPD with significant mitochondrial dysfunction or at higher risk of more rapid progression and facilitate stratification for future precision medicine neu- roprotective trials. Longitudinal studies are required to characterise if changes 31P-MRS measures mirror clinical progression.

ObjectiveTo assess clinical, electrophysiological and whole-body muscle MRI measurements of progression in patients with motor neuron disease (MND), as tools for future clinical trials, and to probe pathophysiological mechanisms in vivo.MethodsA prospective, longitudinal, observational, clinicoelectrophysiological and radiological cohort study was performed. Twenty-nine patients with MND and 22 age-matched and gender-matched healthy controls were assessed with clinical measures, electrophysiological motor unit number index (MUNIX) and T2-weighted whole-body muscle MRI, at first clinical presentation and 4 months later. Between-group differences and associations were assessed using age-adjusted and gender-adjusted multivariable regression models. Within-subject longitudinal changes were assessed using paired t-tests. Patterns of disease spread were modelled using mixed-effects multivariable regression, assessing associations between muscle relative T2 signal and anatomical adjacency to site of clinical onset.ResultsPatients with MND had 30% higher relative T2 muscle signal than controls at baseline (all regions mean, 95% CI 15% to 45%, pConclusionsWhole-body muscle MRI offers a new approach to objective assessment of denervation over short timescales in MND and enables investigation of patterns of disease spread in vivo. Muscles inaccessible to conventional clinical and electrophysiological assessment may be investigated using this methodology.

BackgroundThe anatomical location of the earliest damage in amyotrophic lateral sclerosis (ALS) is still debated. Two main competing hypotheses have been proposed: the dying-forward hypothesis states the damage occurs in the precentral gyrus (PCG) and spreads caudally, which is in contrast with the dying-back hypothesis. This study aims to address this question of directionality of neurodegeneration in vivo using a multimodal neuroimaging approach to derive measures of damage of the motor pathway and analyse them in a common domain.MethodsMRI was performed on 78 ALS patients and 13 controls. PCG thickness was derived from using FreeSurfer, corticospinal tract (CST) fractional anisotropy (FA) from diffusion tensor imaging using FSL, and axial C3 cord area estimates using Philips online software. Comparisons between patients and controls were reported using unpaired t-tests. Parameter estimates were converted to z-scores, referenced to control data, plotted from PCG through CST to cord and directionality of damage assessed by fitting a mixed-effects linear regression model.ResultsZ-scores were not significantly different between PCG and FA (0.24,[95%CI -0.13,0.61], p=0.208) but were significantly lower in FA compared to cross-sectional cord area (-0.85,[95%CI -1.25,-0.46] pDiscussionThis novel multimodal imaging approach supports a dying-forward neurodegenerative process in ALS.

To examine the extent of brain abnormality in patients with coeliac disease referred for neurological opinion and evaluate MR imaging sequences as biomarkers for neurological dysfunction, given the lack of readily available serological markers of neurological disease in this cohort.Retrospective examination of a consecutive cohort of patients (n = 33, mean age = 44 ± 13 years (range 19-64)) with biopsy proven coeliac disease referred for neurological opinion. Patients were divided into subgroups based on their primary neurological complaint (balance disturbance, headache and sensory loss). 3T MR was used to evaluate differences in brain grey matter density, cerebellar volume, cerebellar neurochemistry and white matter abnormalities (WMAs) between subjects and controls.Cerebellar volume was significantly less in the patient group than in controls (6.9 ± 0.7% vs 7.4 ± 0.9% of total intracranial volume, p0.05). Significantly less grey matter density was found in multiple brain regions, both above and below the tentorium cerebelli, than in controls (p0.05). 12 (36%) patients demonstrated WMAs unexpected for the patient's age, with the highest incidence occurring in the headache subgroup. This subgroup averaged almost twice the number of WMAs per MR imaging than the subgroup with balance disturbance and six times more than the subgroup with sensory loss.Patients with established coeliac disease referred for neurological opinion show significant brain abnormality on MR imaging. MR imaging may provide valuable biomarkers of disease in this patient cohort.

Background: The memory deficits in patients with temporal lobe epilepsy (TLE) are associated with epileptogenic lesions of the temporal lobes, especially hippocampal sclerosis. Memory deficits have been extensively studied in TLE, but the presence of pre-existing temporal lobe abnormality has confounded studies on the relationship between memory dysfunction and seizure activity. Idiopathic generalised epilepsy (IGE) is characterised by primary generalised seizures and is found to occur in the absence of any macroscopic brain abnormalities. IGE is therefore ideal for investigations on the effects of seizure activity on memory and cognition. Aim and methods: Magnetic resonance spectroscopy (MRS) and neuropsychological testing were used to investigate the relationship between epileptic seizures, memory performance and neuronal dysfunction in the temporal lobes of a group of patients with IGE. 30 patients and 15 healthy controls participated in the study. Results: Patients with IGE were found to perform worse than controls on tests of speed of information processing, general cognitive performance and a range of memory tests, including face recognition, word recognition, verbal recall and complex figure recall. The performance of the patient group on the visual recognition and verbal recall sections of the Doors and People Test was found to correlate with MRS ratios of N-acetyl aspartate:choline and N-acetyl aspartate:creatine in the temporal lobes. Conclusion: This result supports the hypothesis that memory deficits in epilepsy may be due to neuronal dysfunction secondary to epileptic activity itself in the absence of any macroscopic lesions in the temporal lobes.

OBJECTIVES—To identify by clinical examination, EEG, MRI, and proton spectroscopy, and neuropsychological assessment the prevalence of signs of CNS involvement in patients infected with HIV, and to relate such findings to the evidence of immunosuppression. METHODS—The design was a cross sectional analysis of a cohort of male patients with infected HIV with an AIDS defining diagnosis or low CD4 count (350 compared with seronegative people from a similar background. CONCLUSIONS—Detailed testing failed to disclose significant CNS impairment without immunosuppression in men infected with HIV. Findings from MRI and magnetic resonance spectroscopy (MRS) correlated with those of the neurological examination and neuropsychogical assessment. A combination of such assessments offers a simple surrogate for studies of CNS involvement in HIV disease.

Objective—To investigate MRI and proton spectroscopy changes in five patients with HIV associated dementia complex (HADC) treated with antiretroviral therapy. Methods—Three markers were evaluated: (1) CSF/intracranial volume ratio; (2) T2 weighted signal ratio between parietooccipital white and subcortical grey matter; and (3) metabolite ratios from long echo time (TE=135 ms) single voxel proton spectra of parieto-occipital white matter. Results—Spectroscopic changes indicated initial increases in N-acetyl/(N-acetyl + choline + creatine) ratio (NA/(NA+ Cho+Cr)) and progression of atrophy after initiation of antiretroviral therapy in four of five patients. When the neurological status of the patients subsequently deteriorated (two offive patients), the NA/(NA+Cho+Cr) ratio also declined. Conclusions—spectroscopic changes mirror reversible neuronal dysfunction. These objective, non-invasive techniques may be used for monitoring the neurological eVects of antiretroviral drug therapy in patients with HADC. (J Neurol Neurosurg Psychiatry 1997;63:477‐482)

Introduction Quantitative Electroencephalography (qEEG) has been shown to distinguish AD patients from healthy controls (HC) at a group but not at an individual level. A novel qEEG data analysis method created at the University of Sheffield can measure linear and non-linear levels of brain synchronisation in the time domain. Methods Patients with AD and HV had resting state EEGs. The standard 10–20 international system of EEG electrode placement was used. All patients had MRI and detailed neuropsychology as part of the European VPH-DARE@IT project. Custom made software (Error Reduction Ratio-causality (ERR-causality) analysed average strength of linear and non-linear synchronization in bicentroparietal region. Results 10 HC and 10 AD EEGs were included. Mean ages were 58.1 (AD) versus 62.2 y (HV). Mean mini-mental state examinations were 17.5 (AD) and 28.50 (HV). The ratio of bi-centroparietal synchronisation between eyes open & eyes close (EO/EC) showed a striking difference between the two groups (AD ratio 0.814 versus HC ratio 0.282, p=0.0006). Conclusions These results suggest that patients with AD have higher levels of EO bi-centroparietal synchronisation & in particular the ratio between EO/EC synchronisation has potential to be used as a non-invasive and inexpensive biomarker or diagnostic tool for AD.

Neurology. Second Edition. By p trend, m swash, and c kennard. (Pp 126; £9.50). Published by Churchill Livingstone, Edinburgh, 1997. ISBN 0-443-05807-5. The Colour Guide series covers many specialties, and takes the form of 50-60 of page …