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PurposeThe aim of this study was to re-evaluate the differentiation of patients with dementia with Lewy bodies (DLB) from Alzheimer’s disease (AD) and Parkinson’s disease (PD) using a quantitative analysis of 123I-FP-CIT SPECT scans.MethodsThirty-six patients with in vivo 123I-FP-CIT SPECT and neuropathological diagnoses were included. Based on neuropathological criteria, patients were further subclassified into nine AD, eight DLB, ten PD and nine with other diagnoses. An additional 16 healthy controls (HC) scanned with 123I-FP-CIT SPECT were also included. All images were visually assessed as normal versus abnormal uptake by consensus of five nuclear medicine physicians. Bihemispheric mean was calculated for caudate binding potential (CBP), putamen binding potential (PBP) and putamen-to-caudate ratio (PCR).ResultsPatients with DLB had significantly lower CBP and PBP than patients with AD and significantly higher PCR than patients with PD. Qualitative visual analysis of the images gave an accuracy of 88% in the evaluation of the status of the nigrostriatal pathway considering all individuals, and 96% considering only the patients with PD, AD and DLB. Quantitative analyses provided a balanced accuracy of 94%, 94% and 100% in binary classifications DLB versus AD, DLB versus PD and PD versus AD, respectively, and an accuracy of 93% in the differentiation among patients with DLB, AD and PD simultaneously. No statistically significant differences were observed between the AD and HC.ConclusionsThis study demonstrates a very high diagnostic accuracy of the quantitative analysis of(123I-FP-CIT SPECT data to differentiate among patients with DLB, PD and AD.

An accurate diagnosis of Alzheimer's disease warrants symptomatic treatment with an acetyl cholinesterase inhibitor or, in more severe disease, memantine. Here, the authors discuss the properties of the available treatment options.

Objective:To conduct a validation study of 123I-N-fluoropropyl-2b-carbomethoxy-3b-(4-iodophenyl) nortropane (123I-FP-CIT) SPECT dopaminergic imaging in the clinical diagnosis of dementia with Lewy bodies (DLB) with autopsy as the gold standard.Methods:Patients >60 years of age with dementia who had undergone 123I-FP-CIT imaging in research studies and who had donated their brain tissue to the Newcastle Brain Tissue Resource were included. All had structured clinical research assessments, and clinical diagnoses were applied by consensus panels using international diagnostic criteria. All underwent 123I-FP-CIT imaging at baseline, and scans were rated as normal or abnormal by blinded raters. Patients were reviewed in prospective studies and after death underwent detailed autopsy assessment, and neuropathologic diagnoses were applied with the use of standard international criteria.Results:Fifty-five patients (33 with DLB and 22 with Alzheimer disease) were included. Against autopsy diagnosis, 123I-FP-CIT had a balanced diagnostic accuracy of 86% (sensitivity 80%, specificity 92%) compared with clinical diagnosis, which had an accuracy of 79% (sensitivity 87%, specificity 72%). Among patients with DLB, 10% (3 patients) met pathologic criteria for Lewy body disease but had normal 123I-FP-CIT imaging.Conclusions:This large autopsy analysis of 123I-FP-CIT imaging in dementia demonstrates that it is a valid and accurate biomarker for DLB, and the high specificity compared with clinical diagnosis (20% higher) is clinically important. The results need to be replicated with patients recruited from a wider range of settings, including movement disorder clinics and general practice. While an abnormal 123I-FP-CIT scan strongly supports Lewy body disease, a normal scan does not exclude DLB with minimal brainstem involvement.Classification of evidence:This study provides Class I evidence that 123I-FP-CIT dopaminergic neuroimaging accurately identifies patients with DLB.

Amnestic mild cognitive impairment (aMCI) is a high-risk and often prodromal state for the development of Alzheimer's disease (AD) and is characterised by isolated episodic memory impairment. Functional neuroimaging studies in healthy subjects consistently report left prefrontal cortex (PFC) activation during verbal episodic memory encoding. The PFC activation at encoding is related to semantic processing which enhances memory. The purpose of this study was to ascertain whether impaired verbal episodic memory in aMCI is related to PFC dysfunction. Using functional magnetic resonance imaging (fMRI) we compared 10 aMCI patients with 10 elderly controls during verbal encoding. The encoding task was sensitive to the effects of semantic processing. Subsequent recognition was tested to measure encoding success. Behavioural results revealed impaired recognition and a lower false recognition rate for semantically related distracters (lures) in aMCI, which suggest impaired semantic processing at encoding. Both groups activated left hemispheric PFC, insula, premotor cortex and cerebellum, but group comparisons revealed decreased activation in left ventrolateral PFC in the aMCI group. The magnitude of activation in left ventrolateral PFC during encoding was positively correlated with recognition accuracy in the control group but not in the aMCI group. We propose that verbal episodic memory impairment in aMCI is related to PFC dysfunction which affects semantic processing at encoding.

Background: Dementia with Lewy bodies (DLB) is a common form of dementia. The presence of Alzheimer’s disease (AD) pathology modifies the clinical features of DLB, making it harder to distinguish DLB from AD clinically during life. Clinical diagnostic criteria for DLB applied at presentation can fail to identify up to 50% of cases. Our aim was to determine, in a series of patients with dementia in whom autopsy confirmation of diagnosis was available, whether functional imaging of the nigrostriatal pathway improves the accuracy of diagnosis compared with diagnosis by means of clinical criteria alone. Methods: A single photon emission computed tomography (SPECT) scan was carried out with a dopaminergic presynaptic ligand [ 123 I]-2beta-carbometoxy-3beta-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (FP-CIT; ioflupane) on a group of patients with a clinical diagnosis of DLB or other dementia. An abnormal scan was defined as one in which right and left posterior putamen binding, measured semiquantitatively, was more than 2 SDs below the mean of the controls. Results: Over a 10 year period it was possible to collect 20 patients who had been followed from the time of first assessment and time of scan through to death and subsequent detailed neuropathological autopsy. Eight patients fulfilled neuropathological diagnostic criteria for DLB. Nine patients had AD, mostly with coexisting cerebrovascular disease. Three patients had other diagnoses. The sensitivity of an initial clinical diagnosis of DLB was 75% and specificity was 42%. The sensitivity of the FP-CIT scan for the diagnosis of DLB was 88% and specificity was 100%. Conclusion: FP-CIT SPECT scans substantially enhanced the accuracy of diagnosis of DLB by comparison with clinical criteria alone.

Purpose of review Advances in neuroimaging have expanded its already central role in neurodegenerative disorders.Recent findings The main advances we emphasize are imaging of amyloid in Alzheimer's disease, serial co-registered magnetic resonance imaging in frontotemporal lobar degeneration and imaging of nigrostriatal dysfunction in dementia with Lewy bodies.Summary All of these techniques offer ways of improving diagnosis.

Professor Abe raises the important issue of the involvement of Lewy body disease in the substantia nigra (SN) when making the diagnosis of dementia with Lewy bodies (DLB). It has long been known that, even later on in their illness, about 25% of patients with DLB do not show features of parkinsonism. This is recognized in the consensus criteria for DLB, which do not require parkinsonism for diagnosis. Patients with DLB can have normal dopaminergic imaging because, as with our 3 patients who also had no parkinsonism,1 there is no significant involvement of the SN by Lewy body disease.

Amitriptyline, which is a noradrenaline reuptake and 5-HT reuptake inhibitor, has an established role in the management of chronic tension-type headaches. In a single-blind study, patients with chronic tension-type headache were randomized to either fluoxetine 20 mg (a selective 5-HT reuptake inhibitor) or desipramine 75 mg (a selective noradrenaline reuptake inhibitor) and followed for 12 weeks to compare the effectiveness of the two drugs in improving headache, and to assess whether pain control is related to changes in depression. Patients were evaluated at weekly intervals on an analog pain-rating scale and at 4-weekly intervals on the Montgomery and Asberg Depression Rating Scale (MADRS), the MOS general health status questionnaire (SF36), the Hospital Anxiety and Depression Scale (HADS), and a side effects checklist. Eighteen patients were randomized to take fluoxetine and 19 to take desipramine. Of the 25 patients who completed the trial, 12 were on fluoxetine and 13 were on desipramine. There was no significant difference between the two groups at baseline nor in change of pain; reduction in use of analgesic medication; nor change in the HADS, MADRS, or SF36 scores at 12 weeks, but 72% of patients who completed the study improved, and this improvement almost exactly mirrored the improvement on the MADRS. The results from this trial are compatible with the notion that the beneficial effect of antidepressants in chronic tension-type headache is indirect, mediated by an effect on depression, and not more,dependent on serotonin reuptake inhibition than noradrenaline reuptake inhibition.

Dementia with Lewy bodies (DLB) can at present only be diagnosed with certainty by neuropathological examination. Diagnosis during life remains at best probable, based on the presence of symptoms known from autopsy studies to be frequently associated with DLB. The greatest practical clinical problem lies in distinguishing DLB arid Alzheimer's disease (AD). In DLB there is a considerable degeneration of nigral neurones with depletion of striatal dopamine. In contrast, AD is not associated with significant changes in dopamine metabolism. Iodine-123 iodobenzamide single-photon emission tomography (IBZM-SPET) measures post-synaptic dopamine D2 neuroreceptor availability in the corpus striatum, but is nevertheless a method for assessing the integrity of the nigrostriatal dopaminergic pathway. Sixteen clinically diagnosed DLB patients, 15 normal controls arid 13 AD patients underwent IBZM-SPET. All subjects were scanned 1.5–2 h after intravenous injection of 185 MBq of123I-IBZM. Circular regions of iriterest were employed to calculate radioactivity ratios in each hemisphere as follows: caudate nucleus/frontal cortex, putamen/frontal cortex arid caudate nucleus/putamen. The DLB patients had significantly lower left caudate/putamen ratios (95% confidence intervals: DLB 0.893–0.965, AD 0.972–1.175, controls 1.031–1.168) than either controls or AD patients, and significantly lower right caudate/putamen ratios (95% confidence intervals: DLB 0.926–1.019, AD 0.954–1.103, controls 1.027–1.144) chan controls. Our data suggest that patients with DLB diagnosed by clinical criteria have changes in striatal post-synaptic D2 receptors. This may be of value in distinguishing DLB from AD during life.

Dementia with Lewy bodies (DLB) is part of the spectrum of Lewy body disorders. However, it may be difficult to diagnose patients who have dementia but no Parkinsonism. Visual and semiquantitative assessment of the nigrostriatal dopaminergic nerve terminals in the putamen and caudate nuclei can be obtained with single photon emission computerized tomography (SPECT) using ligands that bind to the dopamine transporter molecule in the membranes of the nigrostriatal nerve terminals. This can be employed as a means of identifying subclinical degeneration of nigrostriatal neurones in patients with suspected DLB, increasing the probability of the diagnosis. In several studies, the sensitivity and specificity of abnormal dopamine transporter scans with regard to diagnosing probable DLB are better than 75 and 90%, respectively. This communication outlines the evidence for this and discusses some of the advantages, potential disadvantages, and areas of uncertainty with regard to the use of dopamine transporter SPECT in DLB diagnosis.

Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) are the common forms of dementia at post-mortem, but distinguishing between these two types of dementia is often very difficult during life. Ioflupane significantly improves the differentiation during life between DLB and AD patients. However, there is a trend for lower caudate uptake in DLB than PD and lower posterior/caudal putamen uptake in PD than in DLB. Further research is needed to test the hypothesis that dopaminergic degeneration may be different, at least regarding anatomical distribution, in DLB and PD. Furthermore, it is important to consider and discuss the potential for ioflupane in the diagnostic workup of patients with DLB.

McAlpine's Multiple Sclerosis. Third edition . By alistair compston, george ebers, hans lassmann, ian macdonald, bryan matthews,and hartmut wekerle. (Pp 562, £99.00.) Published by Churchill Livingstone, London, 1996. ISBN 0443-050082 Those familiar with previous incarnations of McAlpine's Multiple Sclerosis will know that authors have changed from one edition to the next and with that the emphasis has changed as well. This third edition is no exception and it is almost entirely a new book. It has six outstanding authors, each bringing formidable authority to bear on their own and their colleagues' contributions. The book is big and aims at a …

We identified a large Charcot-Marie-Tooth disease family with a novel mutation in the Connexin 32 (Cx32) P2 promoter region at position -526bp. This mutation was in a highly conserved SOX10 binding site. Functional studies were conducted on the Cx32 promoter that showed that this mutation reduced the activity of the Cx32 promoter and the affinity for SOX10 binding. These data suggest that interaction between the Cx32 P2 promoter, SOX10, and EGR2 highlight a mechanism of peripheral nerve dysfunction.

Dentatorubropallidoluysian atrophy is a neurodegenerative disorder with characteristic pathology, chiefly described in reports from Japan, and is associated with an unstable CAG trinucleotide repeat in a gene on chromosome 12. We describe four European families, three British and one Maltese, with this mutation. All exhibited autosomal dominant inheritance, and there was evidence for anticipation associated with an increase of the expansion with paternal transmission in two families. Affected chromosomes from patients with dentatorubropallidoluysian atrophy had CAG expansions of 58 to 74 repeats, compared to 7 to 26 in control chromosomes, and the size of repeat was significantly inversely correlated with age of onset. The clinical features were diverse, even within individual families, and comprised a combination of a movement disorder (chorea, myoclonus, dystonia, or parkinsonism), cerebellar ataxia, epilepsy, psychosis, and dementia. A clinical diagnosis of Huntington's disease had been made in affected individuals from all families. Neuropathological examination of 2 patients showed no specific abnormality in one and degenerative changes predominantly affecting the spinal cord in the other. Investigation of 55 patients who might represent sporadic examples of dentatorubropallidoluysian atrophy did not detect any expanded alleles. Dentatorubropallidoluysian atrophy is likely to be more common than previously recognized in non-Japanese populations, and should be considered in any patient with a dominantly inherited neurodegenerative disorder with the above-mentioned clinical features.

Background:Cerebral white matter changes (WMC) represent cerebrovascular disease (CVD) and are common in dementia. Cholinesterase inhibitors (ChEIs) are effective in Alzheimer's Disease (AD) with or without CVD, and in Dementia with Lewy Bodies/Parkinson's Disease Dementia (DLB/PDD). Predictors of treatment response are controversial.Objective:To investigate the effect of WMC severity on response to ChEIs in dementia.Method:CT or MRI brain scans were rated for WMC severity in 243 patients taking ChEIs for dementia. Raters were blind to patients' clinical risk factors, dementia subtype and course of illness. Effects of WMC severity on rates of decline in cognition, function and behaviour were analysed for 140 patients treated for nine months or longer. Analysis was performed for this group as a whole and within diagnostic subgroups AD and DLB/PDD. The main outcome measure was rate of change in Mini Mental State Examination (MMSE) score. Secondary measures were rates of change in scores on the Cambridge Cognitive Examination (CAMCOG), Instrumental Activities of Daily Living (IADL) and Clifton Assessment Procedures for the Elderly – Behaviour Rating Scale (CAPE-BRS).Results:There was no significant correlation between severity of WMC and any specified outcome variable for the cohort as a whole or for patients with AD. In patients with DLB/PDD, higher WMC scores were associated with more rapid cognitive decline.Conclusions:Increased WMC severity does not predict response to ChEIs in AD, but may weaken response to ChEIs in patients with DLB/PDD.

A 7 year old girl developed acute disseminated encephalomyelitis following a Mycoplasma pneumoniae respiratory infection. The illness followed a relapsing course during the first two months. Computed tomography (CT) showed cerebral lesions of a severity and extent out of proportion to the clinical manifestations. The CT abnormalities altered with changes in her clinical state.