Properties of CA3 dendritic excrescences in Alzheimer's disease.

CA3 pyramidal neurons and hilar mossy neurons possess large and branched dendritic spines, named thorny excrescences. Studies on experimental animals have shown great morphologic adaptation of the excrescences and the whole dendritic tree of CA3 pyramidal neurons in changes of environmental conditions. However, the available data about the excrescences in human brain is short and insufficient about their properties in Alzheimer's disease. In the present study, these dendritic structures were studied and compared in CA3 area of hippocampus in patients suffered from Alzheimer's disease, age matched controls and young individuals. Golgi impregnated material under light microscopy was used for the description of the structural characteristics of the excrescences. Morphometric estimation of their density on the apical and basilar dendritic tree and their average length revealed reduced density and significantly increased size in Alzheimer's disease patients. The mean density of the excrescences on the apical dendritic tree of the patients compared to age matched controls is reduced 32.8% (p<0.001), while the mean number of long excrescences (longer than 5microm) is increased 32.6% (p<0.05). On the basilar dendritic tree, the reduction in density is 26.3% (p<0.05) and the increase in the number of long excrescences is 23.3% (p>0.05). These enlarged thorny excrescences can be even longer than 10microm, appearing as "giant spines". The increased size of the excrescences is considered as a remodeling procedure (compensative mechanism) of the CA3 pyramidal neurons for the balancing of the reduction in the spinal density.

Evaluation of pupil mobility in patients with myasthenia gravis.

The aim of this study is to investigate the effect of Myasthenia Gravis (MG) on the Central Nervous System (CNS) and/or the smooth muscles of the iris through pupillometry. Sixteen recently diagnosed Myasthenic and sixteen non-Myasthenic subjects of matching age and gender underwent a pupillometric study of the effects of single flash stimuli of 24.6 candelas/m2 intensity and 20 msec duration. A significant decrease in Amplitude (p < 0.001), Maximum Constriction Velocity (p < 0.001) and especially Maximum Constriction Acceleration with a perfect discrimination ability (AUC= 1, p < 0.001). was observed in the Myasthenic compared to the non-Myasthenic subjects. In contrast, no significant difference was observed in Baseline Pupil Radius (R1) and 3.5 secs Percentage Recovery-Redilatation (R%) (p = 0.051 and p = 0.517, respectively). Of the parameters that are studied, R1 and R% are governed mainly by the action of the Sympathetic Nervous System (SNS) and the rest by the Parasympathetic Nervous System (ParNS), through Acetylcholine. The analysis of these parameters demonstrates that the SNS remains unaltered while the ParNS may be affected in MG. This post-synaptic cholinergic receptors' deficit may be central, within the CNS, or peripheral, related to the Neuromuscular Junction of the iris' sphincter.

Is it possible to predict the long-term response to venlafaxine with the use of biological markers and psychophysiological methods?

INTRODUCTION: The present study investigated whether it is possible to predict the medium term response to venlafaxine using biological markers and psychophysiological methods. MATERIAL: Fourteen (14) patients aged 21-60 years suffering from Major Depression according to DSM-IV were included in the study. METHODS: The SCAN v 2.0 and the IPDE were used to assist clinical diagnosis. Patients were investigated with electrooculogram (EOG), Pattern-Reversal Visual Evoked Potentials (PR-VEPs), Dexamethasone Suppression Test (DST), D-fenfluramine Challenge Test, and brain Single Photon Emission Tomography (SPECT). Venlafaxine 150-225 mg per os daily was administered. The follow-up period was 2 years. STATISTICAL ANALYSIS: Chi-square test and ANOVA were used for the analysis of data. RESULTS: There was a lower left globus pallidus regional cerebral blood flow in patients with better response. On the contrary, chronic patients were closer to normality. DISCUSSION: The results of the current study provide preliminary evidence concerning our ability to predict response to venlafaxine and to understand its way of action.

Relationship among Dexamethasone Suppression Test, personality disorders and stressful life events in clinical subtypes of major depression: An exploratory study.

: BACKGROUND: The present study aimed to investigate the relationship between dexamethasone suppression test, personality disorder, stressful life events and depression. MATERIAL: Fifty patients (15 males and 35 females) aged 41.0 +/- 11.4 years, suffering from Major Depression according to DSM-IV criteria entered the study. METHOD: Diagnosis was obtained with the aid of the SCAN v 2.0 and the IPDE. Psychometric assessment included the HDRS, HAS, the Newcastle Scale (version 1965 and 1971), the Diagnostic Melancholia Scale, the Personality Deviance Scale and the GAF scale. The 1 mg DST was used. STATISTICAL ANALYSIS: Included MANOVA, ANOVA with LSD post hoc test and chi-square test. RESULTS: Sixteen (32%) patients were non-suppressors. Eight patients without Personality Disorder (PD) (23.5%), and 5 of those with PD of cluster B (50%) were non-suppressors. Atypical patients were the subtype with the highest rate of non-suppression (42.85%). No difference between suppressors and non-suppressors was detected in any of the scales. DISCUSSION: The results of the current study suggest that pathological DST is not a core feature of major depression. They also suggest that there are more than one subtypes of depression, concerning the response to stress. It seems that the majority of depressed patients (50%) does not experience high levels of stress either in terms of self reported experience or neuroendocrine function. The rest of patients however, either experience high levels of stress, or manifest its somatic analogue (DST non-suppression) or have a very low threshold of stress tolerance, which makes them to behave in a hostile way.

Neurophysiological investigation of cervical spondylosis.

The difficulties in diagnosing spinal cord lesions due to the cervical spondylosis is well-known in clinical neurology. In order to investigate the contribution of various neurophysiological examinations in the diagnosis in cervical spondylosis, we examined 70 patients suffering from cervical spondylosis, with peripheral nerve conduction studies, F-wave from the upper limb and electromyography from the corresponding muscles, as well as somatosensory evoked potentials (SEPs) from upper and lower limbs. Patients were separated into four groups: 20 patients had cervical spondylosis symptoms only; 15 patients had symptoms and signs of spinal root involvement; 15 patients had symptoms and signs of myelopathy; and 20 patients had symptoms and signs of both myelopathy and spinal root involvement. A group of 20 normal controls was also studied. In all groups of patients SEPs were the most sensitive electrophysiological study. Low-amplitude N13 and increased conduction time of N9-N13 and central conduction N13-N19 and LP-P27 were the most common finding in SSEP testing. SEPs were affected in many cases without CT-MRI findings of spinal cord pressure. From the above findings, SEPs proved to be the most sensitive diagnostic investigation in cervical spondylosis.

Automated standardized pupillometry with optical method for purposes of clinical practice and research.

The aim of the current study was the introduction and standardization of two experimental conditions for dynamic pupillometry. Pupillometry is a method that can provide valuable data concerning the functioning of the autonomous nervous system. The system for recording the pupil reaction was developed in the Laboratory of Clinical Neurophysiology of the 1st Department of Neurology of Aristotle University of Thessaloniki, in co-operation with the Laboratory of Fluid Mechanics of the Aristotle University of Thessaloniki. This system is fully automated. It includes an infra-red video camera, which has the capacity to record in complete darkness, and an SLE (clinical photic stimulator) lamp. A software application automatically performed all the procedures. During the first experiment, one flash was administered. During the second experiment, a series of 25 flashes (1 Hz frequency) was administered. Fifty physically and mentally healthy subjects aged 23-48 years took part in the study. Means, standard deviations and ranges for all variables characterizing normal subjects during both experimental conditions are reported. Test/re-test results and comparisons of the two eyes are also reported. The combined use of these two experimental conditions in dynamic pupillometry may be a very useful tool in medical research. There are already reports on the usefulness of pupillometry in the research of various diseases, including depression and Alzheimer's disease. It is expected that it will also be a valuable research tool in the study of diabetes, alcoholism, myasthenia gravis, cancer, multiple sclerosis, etc.

Changes in pupil reaction to light in Alzheimer's disease patients: a preliminary report.

The aim of this preliminary study was to compare the pupil reaction to light in Alzheimer's disease (AD) patients before and after treatment and in normal controls. Ten AD patients diagnosed according to DSM-IV and NINCDS-ADRDA criteria (five medication-free and five under anticholinesterase treatment) and five age- and gender-matched controls took part in the study. Drug-free patients and all control subjects were free of any medication for at least four weeks. An optical method was used to assess the pupil reaction to a single flash. Medication-free AD patients manifested shorter latency and lower amplitude of maximum response to light in comparison to controls. These findings are in agreement with the presence of a cholinergic deficit in AD patients. Pharmacological treatment with donepezil, which is an anticholinesterase agent partially improves this deficit. The results of this preliminary investigation suggest that dynamic pupillometry could be a useful adjunct to assist the diagnosis of early AD, and the differential diagnosis between different types of dementia. AD patients seem to manifest a specific pattern of pupil reaction to light, and some characteristics of this pattern are detectable even in patients receiving anticholinesterase medication. However, this is only a preliminary report and further research is mandatory.

Do depressive patients with family history of dementia constitute a separate group? A case report study.

INTRODUCTION: Recently it has been suggested that patients with both depression and a family history of dementia are seven times as likely to develop Alzheimer's disease as are controls. METHOD: Fifty patients aged 21 - 60 years suffering from DSM-IV Major Depression entered the study; three of them (6%) had a positive family history of dementia. Diagnosis was by SCAN v 2.0. The family history method was used to record family history. All depressed patients were investigated with the Dexamethasone Suppression Test (DST), brain SPECT, electro-oculogram (EOG), flash-electroretinogram (f-ERG) and Pattern-Reversal Visual Evoked Potentials (PR-VEPs). Student's t-test was used to analyse the results. All patients with positive family history had atypical features. RESULTS: Two of them suffered from borderline personality disorder, in comparison to eight in the remainder of the sample and five in the rest of the atypicals. The age of onset of depression was lower. DST, SPECT, EOG and PR-VEPs findings were similar between groups. The only significant finding concerned the latency of the bs wave of the scotopic ERG (P < 0.01), but even in this, patients with positive history did not differ from the rest of the atypical patients. CONCLUSION: The present study provided limited data connecting atypical features of depression, personality traits, psychological stressors, hypercortisolaemia and family history of dementia. Further research with larger samples is essential. ( Int J Psych Clin Pract 2000; 4: 215 - 222).

The value of neurophysiological and MRI assessment in demyelinating optic neuritis (DON).

PURPOSE: To study, by neurophysiological means, the possible involvement of the retina, in demyelinating optic neuritis (DON). MATERIAL AND METHODS: Thirty-five patients fulfilling strict criteria of unilateral DON were investigated with a battery of neurophysiological tests and MRI within 3 weeks of the onset of their symptoms. Flash-ERG (F-ERG) in photopic conditions, Flash-VEPs and PR-VEPs were recorded. MRI of the brain and the optic nerve were performed. RESULTS: The amplitude of b-wave of F-ERG in photopic conditions was statistically significantly lower in the affected eye (p < 0.001) compared to normal controls, whereas in the unaffected eye, it was also statistically significantly lower than normal controls (p < 0.01). All patients had statistically significant prolongation of P100 latency in PR-VEPs of the affected eye (p < 0.001) in comparison to normal controls. The P100 wave of the unaffected eye was also delayed (p < 0.01). In MRI, Gd-DTPA enhancement was observed in 7 symptomatic nerves with only minimal enhancement of the optic nerve between optic chiasm and optic canal, whereas 11 patients were presented with intracranial associated plaques. Five of the above patients had optic nerve enhancement and diffused demyelinating findings simultaneously. CONCLUSION: These results are a neurophysiological indication of involvement of the retina in DON, probably of vascular origin.

Changes in pupil reaction to light in melancholic patients.

The aim of the current study was to compare the pupil reaction to light in depressed patients and normal control subjects. Seven depressed patients with melancholic features according to DSM-IV criteria and 14 age- and gender-matched control subjects took part in the study. All were free of any medication for at least 2 weeks. All were aged between 25 and 50 years. An optical method was used to assess the pupil reaction to a single flash. Depressed patients manifested shorter latency for constriction than control subjects, and a marginal difference in the total work produced by acetylcholine. The results of the current study support the theory that there is a norepinephrine hypoactivity in melancholic depression, with less affected acetylcholine activity.

Changes in psychophysiological processing of vision in myasthenia gravis.

OBJECTIVE: To investigate the possibility of impaired central nervous system (CNS) cholinergic transmission in myasthenia gravis (MG), and the effect of eye movements and particularly of micromovements in the psychophysiology of vision. MATERIALS AND METHODS: Fourteen patients with clinical manifestations of external ophthalmoplegia due to different causes (nine patients with myasthenia gravis and five with ocular myopathy) were examined. Simultaneous recording of eye movements (optical method) and pattern reversal-visual evoked potentials (PR-VEPs) were performed. RESULTS: Eye micromovements during fixation were impaired in both groups. A statistically significant difference (P < 0.01) was found in the amplitude of P100 of PR-VEPs before and after treatment in MG patients, and also between normal controls and MG patients before (P < 0.001) and after treatment (P < 0.01). P100 latency of the PR-VEPs in MG patients before and after treatment was delayed compared to normal controls, while there were no differences between ocular myopathy patients and normal controls. CONCLUSION: The eye movement impairment observed in MG patients is not sufficient to explain abnormal PR-VEPs detected in these patients. These results provide neurophysiological evidence of impaired cholinergic transmission in the central nervous system in patients with MG and suggest that PR-VEPs offer an easily applicable non-invasive method to study the central effects of MG.

Dermatomal SEPs--a complementary study in evaluating patients with lumbosacral disc prolapse.

We investigated the value of Dermatomal Somatosensory Evoked Potentials in 24 patients with unilateral radiculopathy due to lumbosacral disk prolapse. All patients had clinical signs and symptoms of disk prolapse and positive findings on neuroradiologic testing. We assessed the latency and the amplitude of the first positive waveform of Dermatomal SEPs, as well as conducting peripheral nerve conduction studies and electromyography. Our studies showed a clear correlation of Dermatomal SEP abnormalities and radiculopathy in up to 83.3% of subjects studied. Use of electromyography testing provided this correlation in about 62.5% of the same subjects. On the basis of these results, we propose that Dermatomal SEPs have value in complementing the routine electrophysiological testing of the patients with radiculopathy and provide a sensitive non-invasive technique for defining the level of disk prolapse.

Comparison of dermatomal SEPs and operative findings in lumbar disc disease.

This report deals with an estimation of the diagnostic value of dermatomal somatosensory evoked potentials (SEPs), by correlating the neurophysiological data to clinical, neuroradiological and operative findings in lumbar disc protrusion. Our material consists of 12, surgically treated patients with lumbar disc protrusion in which diagnostic work up included history, neurological examination, routine lumbar spine films, computerised tomography and MRI of the lumbar spine, in addition to neurophysiological investigation, especially conduction velocity studies, and SEPs recorded by the standard methods, as well as after dermatomal stimulation. The retrospective analysis disclosed a correlation for the SEPs after dermatomal stimulation and surgical findings, in 83% of our cases.

Changes in the pattern reversal visual evoked potentials in myasthenia gravis.

To investigate the possibility of impaired cholinergic transmission in the Central Nervous System (CNS) in patients with Myasthenia Gravis (MG), the PR-VEPs in 11 newly diagnosed MG patients before and after pyridostigmine treatment compared to those recorded from 10 normal subjects tested in two different occasions one month apart. All patients, (7 female and 4 male) had a good response to treatment. The amplitude of the P100 of the PR-VEPs of the MG patients before and after treatment was significantly lower than those recorded from the normal control subjects and the latency significantly longer. In the patient group the amplitude of the P100 improved significantly after treatment. These results provide neurophysiological evidence of impaired cholinergic transmission in the CNS in patients with MG and suggest that PR-VEPs offer an easily applicable non-invasive method to study the central effects of MG and possibly a procedure to monitor the effectiveness of pyridostigmine treatment.

Automated rate nephelometric determination of apolipoproteins AI and B in human serum by consecutive addition of antibodies.

A precise, rapid, automated, rate nephelometric immunoassay for apolipoprotein AI (APA) and apolipoprotein B (APB) is described. Both analytes are determined by a "one-pot" procedure which uses consecutive addition of the corresponding antibodies. Poly(oxyethylene) type nonionic surfactants are used to selectively inhibit the APB reaction after the maximum reaction rate has been reached and to enhance the APA immunoreactivity. The assay range for APA is 0.3-3.8 g/L and for APB 0.2-3.0 g/L. The new assay was compared to commercial rate nephelometric methodology. Both methods were shown to be mutually unbiased for APA and APB determinations in human serum.

Effect of N-REM sleep on the cortical SEPs in early life.

Cortical and cervical somatosensory evoked potentials (SEPs) were studied by the averaging method in twenty healthy children, aged 20 days to 3 years. The stimulus was applied to the median nerve at the wrist and SEPs were recorded by electrodes placed on to the contralateral parietal scalp region as well as over the skin at the C6-7 vertebral region. The reference electrode was placed at the Fz. All subjects were studied during the awake state as well as during the N-REM sleep. The results indicate that N-REM sleep influenced the latency and the duration of SEPs, especially in children aged less than one year. This finding probably reflects a variable rate of maturation of the somatosensory pathway. The state of wakefulness must therefore be taken into account when assessing the pathological relevance of SEP recording in young children.

The electroretinogram in multiple sclerosis and demyelinating optic neuritis.

The electroretinogram (ERG) to flashes of white light presented under photopic conditions and the pattern reversal visual evoked potentials (PR-VEPs) from both eyes were recorded from 14 patients with multiple sclerosis (MS) with monocular demyelinating optic neuritis (DON) and from 11 patients soon after presenting with monocular demyelinating optic neuritis alone. Fifteen and 10 normal subjects, matched for age and sex, were used as controls for each group of patients respectively. In the DON group of patients and controls the flicker following ERG (FF-ERG) to white flashes of light at 40 Hz was also recorded. Skin electrodes and averaging procedures were used for all the recordings. The PR-VEP elicited with stimulation of the affected eye was absent or abnormally delayed, and the amplitude of the 'b' wave of ERG of the affected eye was diminished in all patients. The 'b' wave latency, however, was similar in both affected and non-affected eyes and the controls. There was no difference in 'a' wave amplitude and latency between eyes of patients and normal subjects. The FF-ERG in 8 out of 10 patients with satisfactory recordings was diminished in the affected eye. These results provide neurophysiological evidence that retinal damage is not due to loss of myelin but is an early feature of demyelinating optic neuritis. This damage preferentially affects the retinal elements associated with the generation of the 'b' wave of the ERG, probably the glial cells of Müller.