Neuropsychological patterns underlying anosognosia in people with cognitive impairment.

AIMS: To investigate, in a group of subjects with cognitive impairment, the relationship between anosognosia, in each dimension of insight, and neuropsychological domains. METHODS: Two hundred and seventy-one subjects affected by cognitive impairment were consecutively enrolled. Anosognosia was evaluated by means of the Clinical Insight Rating Scale (CIRS). The general level of cognitive impairment was evaluated by means of the Mini-Mental State Examination, while 8 cognitive domains were examined by means of neuropsychological tests. RESULTS: The number of subjects with anosognosia evaluated by means of the CIRS total score as well as those with anosognosia divided according to the reason for visit was higher in moderately cognitively impaired subjects than in mildly cognitively impaired subjects (p < 0.001). A relationship between anosognosia and neuropsychological scores was only found in mild cognitive impairment, with subjects with anosognosia displaying significantly lower Raven's Colored Progressive Matrices Test and Rey Auditory Verbal Learning Test-delayed recall scores than subjects without anosognosia. CONCLUSIONS: Our study suggests that the relationship between the severity of cognitive deficits and anosognosia in subjects with cognitive impairment is partial and depends on the specific domain of unawareness. Furthermore, in the early phase of cognitive impairment, the presence of specific cognitive deficits suggests that the nature of anosognosia is domain-specific.

White matter damage along the uncinate fasciculus contributes to cognitive decline in AD and DLB.

This study investigates the patho-physiological implications of the uncinate fasciculus (UF) in the two most common forms of dementia, namely Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). Forty-five consecutive patients diagnosed with either probable AD or DLB, and 16 individuals with amnesic mild cognitive impairment (a-MCI) were investigated using diffusion tensor MRI. Thirteen healthy subjects (HS) were also studied as controls. In each subject, the UF was bilaterally reconstructed by probabilistic tractography. From each UF, macroscopic volume and correspondent fractional anisotropy (FA) (an index of microscopic white matter integrity) were derived for the whole tract, and for the frontal and temporal portion of the UF. No significant between-group volumetric differences were found. In contrast, FA values from the UF were reduced bilaterally in patients with dementia (either AD or DLB) compared to HS. In addition, patients with AD showed reduced FA values compared to those with a-MCI. No significant FA difference was found between AD and DLB patients, nor between a-MCI and HS. Finally, in all patients, UF FA values were associated with neuropsychological scores at tests exploring memory and executive functions. This study indicates that the UF is remarkably damaged in patients at the stage of dementia, independently from the diagnostic form. Moreover, this UF damage seems to be driven by temporal involvement in AD, for which a prodromal stage (a-MCI) is defined.

Vascular risk factors and white matter hyperintensities in patients with amnestic mild cognitive impairment.

BACKGROUND: Subjects affected by aMCI are considered at high risk for AD. Nevertheless, the role of both vascular risk factors and WMH is matter of debate. PATIENTS AND METHODS: We enrolled consecutively 21 aMCI subjects according to Petersen Criteria; the study included routine screening for dementia, neuropsychological evaluation and brain MRI. Six vascular risk factors were assessed and WMH was quantified by means of a semiautomatic lesion-detection program. RESULTS: Conversion to AD, according to NINCDS-ADRDA criteria, was 47.6%. Converters tended to be more affected by the most of vascular risk factors while no difference was noted in WMH. The best predictors of conversion to AD were scores obtained at several neuropsychological examination. CONCLUSION: Our results show that criteria for aMCI identify subjects with a high risk to develop AD. WMH doesn't seem to have a role in progression from aMCI to AD, while some vascular risk factors seem to promote it.

MRI evidence of bilateral hippocampal sclerosis in amnestic mild cognitive impairment.

We present the case of a man affected by amnestic mild cognitive impairment (aMCI) who showed bilateral hippocampal sclerosis at magnetic resonance imaging (MRI). We argue the concept that aMCI is heterogeneous syndrome and suggested the utility of coronal T2-weighted MRI images in the routine dementia workup.

Cerebral atrophy in myotonic dystrophy: a voxel based morphometric study.

Brain involvement in myotonic dystrophy type 1 (DM1) is characterised by cortical atrophy and white matter lesions. We compared the magnetic resonance imaging derived grey matter maps of 22 DM1 patients with those of matched, healthy controls using voxel based morphometry to evaluate the extension of global and regional cortical atrophy in DM1, as well as its relationships with clinical and genetic features. Patients had significantly reduced brain tissue volumes. Grey matter volume was inversely correlated with age; this inverse correlation was significantly stronger in DM1 than in controls. Neither the clinical and genetic characteristics nor white matter lesions were correlated with cortical atrophy. Grey matter atrophy was located mainly in the bilateral frontal and parietal lobes, in the bilateral middle temporal gyrus, and in the left superior temporal and occipital gyrus.

Apraxia of eyelid opening in a case of atypical corticobasal degeneration.

Apraxia of eyelid opening (AEO) occurs in several clinical conditions, even in the absence of any other neurological sign; nonetheless, in most of the cases AEO has been reported in association with basal ganglia diseases, such as corticobasal degeneration (CBD). We describe a patient with a clinical diagnosis of frontotemporal dementia who, later, developed parkinsonian signs and AEO. We suggest that the finding of AEO in patients with a frontotemporal syndrome could be a helpful expedient for the early diagnosis of atypical clinical findings of CBD, characterised by behavioural and cognitive aspects at first.

Autoantibodies to glutamic acid decarboxylase in downbeat nystagmus.

The cause of downbeat nystagmus (DBN) remains undiagnosed in about 40% of patients. This paper reports the presence of antiglutamic acid decarboxylase antibodies (GAD-Ab) in a patient with DBN. Antibodies against GABAergic neurons located in the vestibular complex may induce chemical denervation of the floccular neurons, which normally suppress the peripheral imbalance between vertical semicircular canal systems, thereby causing DBN. Testing for GAD-Ab may be indicated in DBN patients without an identifiable anatomical brain lesion.

Blood cholesterol and MRI activity in first clinical episode suggestive of multiple sclerosis.

OBJECTIVES: The present study was planned to investigate the relationship between the plasma lipid profile and disease activity in patients with a first clinical episode suggestive of multiple sclerosis (MS). MATERIAL AND METHODS: Eighteen consecutive out-patients underwent a monthly brain magnetic resonance imaging (MRI), blood sample and neurological assessment over 6 months. Blood samples were used to evaluate total cholesterol and triglyceride levels as well as their lipoprotein fractions. Plasma total apolipoprotein E concentration was also determined. RESULTS: We found a significant correlation between the mean number of enhancing lesions and the mean plasma level of both total and low density lipoprotein cholesterol. The total plasma cholesterol level increased on average by 4.4 mg/dl for each enhancing lesion. CONCLUSION: Our preliminary data suggest a potential role of plasma cholesterol level as a biological marker of disease activity after a first demyelinating event. Further studies need, however, to be designed to determine whether the plasma cholesterol level is of practical use in monitoring the disease course.

Altered circadian cortisol secretion in Alzheimer's disease: clinical and neuroradiological aspects.

We determined circadian salivary cortisol levels in 18 outpatients affected by probable Alzheimer's disease (AD) and looked for a possible correlation with both cognitive impairment and brain CT scan findings. The diagnosis of probable AD was made according to the NINCDS-ADRDA criteria. The severity of cognitive impairment was quantified using the Mini Mental State Examination (MMSE) and the Global Deterioration Scale (GDS). Cortisol levels were measured on saliva samples collected at 08:00 AM and 08:00 PM. For each sample, a duplicate cortisol measurement was performed on 50 microl of saliva by means of a modified commercial radioimmunoassay kit. At the same time, 11 of the 18 AD patients enrolled also underwent a brain CT scan to estimate cerebral atrophy by using linear indexes. The mean value of cortisol levels was significantly higher in AD patients than in controls at both the morning and the evening measurements, and the circadian fluctuation of cortisol was less marked in AD patients than in controls, although this difference did not reach statistical significance. Morning cortisol levels were significantly correlated to both the MMSE and the GDS scores. A significant correlation was also found between morning cortisol levels and all the cerebral atrophy indexes. By contrast, no correlation was observed between evening cortisol levels or cortisol circadian fluctuations and either cognitive impairment or cerebral atrophy. In conclusion, despite the potential biases deriving from the small sample and the limitations of the CT scan study, our results suggest that, in AD patients, hypercortisolemia is correlated with severity of the disease.

Satellite potentials on EMG: neurophysiologic evidence of axonal transection in MS?

To detect signs of axonal damage in MS, the authors investigated the occurrence in EMG of motor unit action potentials with satellite potentials (SP-MUAP) in the upper limb muscles in 10 consecutive patients with MS with cervical spinal cord demyelinating lesions and 10 control subjects. Subjects' SP-MUAP rate was 0 to 2.5% (median 0%) in the control group, and 0 to 17.5% (median 7.5%) in the MS group (p < 0.01). Motor unit remodeling secondary to axonal transection of spinal motor neurons traversing cervical demyelinating lesions may be hypothesized.

T cell response to N-formylated peptides in humans.

We present the first evidence of a T lymphocyte response to N-formylated peptides in humans. N-formylated peptide sequences from self (mitochondrial) and foreign (microbial) antigens were used to isolate antigen-specific T cell clones from healthy individuals, including a set of monozygotic twins. The observed response differed from that previously described in mouse (CD4(+) phenotype and MHC class II restriction in humans vs. CD8(+) phenotype and class I restriction in mice). These lymphocytes produce substantial amounts of IFN-gamma. They were isolated in only one of the monozygotic twins, which suggests that their expansion in the healthy immune repertoire is independent of the genetic background. Our result will help in assessing the relevance of N-formylated peptide-specific T cells in protection against infections within the human immune system.

Intrastriatal injection of D1 or D2 dopamine agonists affects glucose utilization in both the direct and indirect pathways of the rat basal ganglia.

Two distinct pathways are thought to connect the striatum to the basal ganglia output nuclei: a direct pathway, originating from neurons bearing dopamine, D(1) receptors and an indirect pathway, originating from neurons expressing D(2) receptors. It has been recently suggested, however, that dopamine receptor sub-types may co-localize and co-operate in the striatum. We sought to verify the functional segregation of the two pathways by measuring cerebral glucose utilization following intrastriatal injection of selective D(1) (SKF 38393), D(2) (quinpirole), or non-selective indirect (amphetamine) and direct (apomorphine) dopamine agonists, in freely-moving rats. All drugs -- regardless of receptor selectivity -- reduced glucose utilization in nuclei of both the direct and indirect pathways, thus lending further support to the existence of a functional co-operation of striatal D(1) and D(2) receptors.

Natural history of cardiac involvement in myotonic dystrophy: correlation with CTG repeats.

The authors prospectively studied the natural course of cardiac involvement and its relationship to cytosine-thymine-guanine (CTG) expansion in 50 patients with myotonic dystrophy who were submitted to periodic cardiovascular EKG and EKG-Holter monitoring during a median follow-up of 56 months. Nineteen patients (38%) developed major EKG changes. CTG length was not correlated with the frequency of EKG abnormalities, but was inversely correlated with the age at onset of EKG abnormalities (p < 0.0001). CTG length influences the timing of cardiac complications in myotonic dystrophy.

Myelin basic protein intramolecular spreading without disease progression in a patient with multiple sclerosis.

A case with stable multiple sclerosis (MS) and T cell responses which initially focused on peptide 16-38 of myelin basic protein (MBP) allowed us to investigate the dynamics of the MBP-specific T cell repertoire and its relationship with disease progression. Epitope mapping experiments and T cell receptor usage of MBP-reactive T cell lines (obtained at four distinct time points over a 7-year period) showed a spreading of the response. Transient expansions and persistence of T cells recognizing different MBP epitopes were also detected. The patient's expanded disability status scale and magnetic resonance imaging lesion load remained stable. Our case shows both persistent self-recognitions and determinant spreading in stable MS. This finding suggests that the relationship between dynamics of self-recognition and disease progression is highly complex.

Reading latency of words and nonwords in Alzheimer's patients.

Contrasting data on reading ability in Alzheimer's disease patients have been reported in the literature. Recently Patterson, Graham and Hodges (1994) found that irregular words were misread by demented subjects, while regular words were read correctly. The present study hypothesizes that reading latency may be a sensitive measure of Alzheimer's patients reading impairment. Fifteen Alzheimer's patients were compared with 17 elderly normal subjects on three tasks that used the same set of concrete, regular words: a picture naming task, a word-picture matching task and a word-nonword reading task. The results of the study indicate that reading latency is longer in Alzheimer's patients than in normal subjects, and that misnamed and mismatched words are read with the same mechanism as nonwords.

Preserved blood pressure and heart rate circadian rhythm in early stage Alzheimer's disease.

BACKGROUND: This study investigated the blood pressure (BP) values over the day-night period in 11 noninstitutionalized patients affected by probable Alzheimer's disease (AD) in its early stage. The scientific aim was to detect whether the BP circadian rhythm (CR) was preserved, given the fact that CR disruption was observed in advanced or institutionalized AD patients. METHODS: The BP within-day values were gathered via noninvasive ambulatory monitoring. The BP time series were analyzed according to the chronobiological procedure, called Cosinor method with three harmonic components. RESULTS: The biometric analysis was able to document that BP changes over the 24-h scale in AD patients as a function of a significant CR. Such a preserved circadian regulation is, however, compromised in the second and third harmonic component, suggesting that the BP within-day variability is desynchronized by the environmental clues that act as synchronizers during the diurnal part of the day. CONCLUSIONS: The preservation of the BP CR in the early stage of AD suggests using such a finding as a clinical tool for confirming the recent onset of the disease. As a matter of fact, it is presumed that the disease is not evolved enough to reach the suprachiasmatic nuclei, wherein is located the BP circadian pacemaker. The abolition of the ultradian components is another precocious sign that, in turn, indicates early-stage AD patients to be particularly compromised in their synchronization to diurnal cues, such as social routines, meal timing schedule, psycho-physical activity, and occupational schemes.

Excessive daytime sleepiness in myotonic dystrophy.

The aim of the present study was to assess whether or not there is any correlation between magnetic resonance imaging (MRI) abnormalities and excessive daytime sleepiness (EDS) in a consecutive series of patients with myotonic dystrophy (MD). The influences of nocturnal breathing abnormalities and sleep morphology on EDS were also evaluated. Ten MD patients were studied by means of an all-night polysomnographic recording, the multiple sleep latency test (MSLT) and MRI. Diagnosis of MD was established on the basis of the clinical and electrophysiological evidence of myotonia as well as of the characteristic genetic pattern. No patient had respiratory failure. Polysomnography and MSLT were also evaluated in ten healthy age-matched controls under the same environmental conditions. The mean MSLT value was significantly lower in patients than in controls. Five of the ten patients were found to have pathological EDS. The quantitative sleep variables and the nocturnal apnoeas in these five patients were not significantly different from those of the patients without EDS. As two patients did not undergo MRI because of claustrophobia, the MRI data were considered in eight patients. Corpus callosum (CC) atrophy was detected in four patients, whereas three patients showed hyperintense areas in the white matter. No correlation was found between EDS and MRI indexes of subcortical atrophy as well as volume of the hyperintense areas. By contrast, a correlation was found between the MSLT value and the reduction in the anterior area of the CC. Our data suggest that CC atrophy might occur in MD patients, and that the size of the CC anterior area might be associated with EDS.

Autonomic nervous activity during sleep in middle cerebral artery infarction.

No data are available on the autonomic system during sleep in patients with stroke. The purpose of this study was to determine the influence of acute ischemic stroke on the autonomic cardiovascular system during sleep, and to correlate autonomic activity with the clinical status of patients. Ten patients with ischemic stroke in the middle cerebral artery were studied by means of an all-night polysomnographic recording within the 1st week of the onset of symptoms and at the 3-week follow-up examination. Power spectrum analysis of the heart rate variability was performed using an autoregressive algorithm in 180 consecutive electrocardiographic RR intervals. Spectral power was calculated in 3 main frequency bands: high frequency (HF), 0.15-0.4 Hz; low frequency (LF), 0.04-0.15 Hz; very low frequency (VLF), < 0.04 Hz. The data were compared with those of 10 age-matched controls. A significant increase in VLF (p < 0.0005) and a decrease in HF (p < 0.0002) components were found in ischemic stroke patients. The sympathetic-parasympathetic balance (VLF + LF/HF) was higher in patients than controls (p < 0.005). However, these components changed significantly during sleep, revealing a physiological pattern. These power spectral data were still present at the 3-week follow-up. The 4 patients who developed cardiac arrhythmias showed higher sympathetic-parasympathetic balance than patients without arrhythmias (p < 0.05). These data suggest a sympathetic predominance in patients with acute ischemic stroke during sleep. However, the flexible and dynamic properties of the autonomic nervous system are preserved. Cardiac arrhythmias following stroke may be related to the degree of sympathetic predominance.

Long-term prognosis after a minor stroke: 10-year mortality and major stroke recurrence rates in a hospital-based cohort.

BACKGROUND AND PURPOSE: Determinants of long-term outcome are not well defined in minor stroke patients. This study aims to evaluate which factors are independent long-term predictors of death and major stroke recurrence in a cohort of minor ischemic strokes. METHODS: A cohort of 322 patients with first-ever minor ischemic strokes (mean age, 55 years; 89% were treated with antiplatelet or anticoagulant drugs) with minor (Rankin score=2) or no disability (Rankin score <2) were followed for 10 years, with only 6% lost to follow-up. Death and major stroke recurrence rates were evaluated by Kaplan-Meier analysis. Hazard ratios and 95% confidence intervals (CI) of factors with P<.1 at the log-rank test were evaluated by multivariate Cox analysis. RESULTS: The 10-year mortality rate was 32%, with a relative risk of 1.7 (95% CI, 1.4 to 2.1) compared with the age- and sex-matched general population. The 10-year recurrence rate of major strokes was 14%. The hazard ratio (95% CI) of death was 1.1 (1.05 to 1.09) for age (1-year increments), 3.4 (2.2 to 5.2) for minor disability, 1.8 (1.1 to 3.1) for myocardial infarction (MI), 2.0 (1.1 to 3.7) for nonvalvular atrial fibrillation, and 1.8 (1.2 to 2.7) for hypercholesterolemia. The hazard ratio (95% CI) of major stroke recurrence was 2.8 (1.3 to 6.2) for recurrent minor strokes, 3.1 (1.9 to 4.6) for nonlacunar stroke, 2.9 (1.3 to 6.8) for MI, and 3.0 (1.4 to 6.4) for hypertension. CONCLUSIONS: In minor ischemic strokes, age, minor disability, MI, nonvalvular atrial fibrillation, and hypercholesterolemia increase the risk of death; recurrent minor strokes, nonlacunar stroke, MI, and hypertension increase the risk of major stroke.

Cardiac autonomic dysfunction in patients with Alzheimer disease: possible pathogenetic mechanisms.

We studied a possible correlation between autonomic cardiac activity and the level of the red blood cell acetylcholinesterase (AChE) in patients with probable Alzheimer disease (AD). The influence of cholinesterase inhibitor treatment on this autonomic activity was evaluated. Twelve patients satisfying the NINCDS-ADRDA criteria of probable AD and 10 healthy controls were studied. Autonomic cardiac activity was evaluated by means of power spectral analysis (PSA) of heart rate variability (HRV) using an autoregressive algorithm on 250 consecutive electrocardiographic R-R intervals. All patients received oral eptastigmine, a new cholinesterase inhibitor, for 1 month. Before treatment, a simultaneous recording of the electrocardiographic and respiratory activities was performed at rest and subsequently during head-up tilt test at 700. Recording was repeated on the last day of treatment. The level of AChE activity during each recording was also evaluated. Spectrum power was calculated in three main frequency bands: high frequency (HF), 0.15-0.4 Hz; low frequency (LF), 0.04-0.15 Hz; very low frequency (VLF), <0.04 Hz. In addition, we calculated the total spectrum power (TSP) and the LF/HF ratio. The TSP and the absolute value of each spectral component were significantly lower in AD patients than in controls. In contrast with controls, AD patients did not show any significant change before treatment in either the LF and HF components or in the LF/HF ratio during the tilt test. However, the modification in the LF component, induced by tilting, showed a significant correlation with the level of AChE activity (p < 0.03). During the tilt test, the treatment caused changes in LF and HF components and in the LF/HF ratio similar to those observed in controls. These results suggest that the presence of autonomic cardiac dysfunction in AD patients might be due to a cholinergic deficit in the peripheral autonomic nervous system. Some aspects of this autonomic dysfunction can be normalized by cholinesterase inhibitor treatment.