Dimitrios Fotiou

Cholinergic deficiency in Alzheimer's and Parkinson's disease: Evaluation with pupillometry

The aim of the study was to evaluate the cholinergic deficiency in Alzheimers (AD) and Parkinsons disease (PD). For this purpose, pupil size changes and mobility were assessed using a fast-video pupillometer (263 frames/s). Twenty-three (23) patients with probable AD and twenty-two (22) patients with PD (eleven with cognitive impairment and eleven without) entered the study. A full record of the pupils reaction to light was registered. From this data ten (10) parameters were measured and reported. Comparison of those parameters in both group of subjects followed. Patients with probable AD had abnormal pupillary function compared to healthy ageing. All the Pupil Light Reflex (PLR) variables significantly differed between the two groups (p<0.005) except the Baseline Pupil Diameter after 2-min dark adaptation (D1) and the Minimum Pupil Diameter (D2). Maximum Constriction Acceleration (ACmax) was the best predictor in classifying a subject as normal or as an AD with a perfect classification ability (AUC=1, p<0.001). ACmax and Maximum Constriction Velocity (VCmax) were significantly lower in PD patients without and with coexisting cognitive impairment compared to normal subjects (p<0.001). Patients with cognitive impairment had significantly lower levels of ACmax, VCmax and amplitude (AMP=D1-D2) than patients with no cognitive deficits. ACmax and secondarily VCmax were the best predictors in classifying a subject as normal or as a PD patient with or without cognitive impairment. Cognitive and memory impairment, which reflects a cholinergic deficit, may be a crucial pathogenetic factor for the decrease in the aforementioned pupillometric parameters. VCmax and ACmax can be considered as the most sensitive indicators of this cholinergic deficiency.

Morphological Changes of the Human Purkinje Cells and Deposition of Neuritic Plaques and Neurofibrillary Tangles on the Cerebellar Cortex of Alzheimer’s Disease

Alzheimer’s disease is a neurodegenerative disorder, characterized by progressive decline in memory and in social performance. The morphological hallmarks of the disease are neuronal loss, loss of dendritic spines, neurofibrillary degeneration and neuritic plaques mainly in the hippocampus and the cortex of the cerebral hemispheres. This study is based on the morphological analysis of the cerebellar cortices of eight brains, 4 patients suffered from Alzheimer’s disease and 4 normal controls, by Golgi method, as well as Nissl, Gallyas’, Bielschowsky’s, Methenamine Silver staining and Congo red methods. Although typical neuritic plaques were not seen in the cerebellar cortex and the diffuse plaques found in the cerebellum in far smaller proportion than plaques in the prefrontal and parietal cortices of the same cases, Golgi impregnation technique revealed a loss of Purkinje cells and a marked decrease in the density of dendritic arborization.

Dendritic Pathology and Spinal Loss in the Visual Cortex in Alzheimer's Disease: A Golgi Study in Pathology

ABSTRACT Alzheimers disease is a neurodegenerative disorder characterized by progressive decline in memory, loss of professional skills, impairment of judgement and behavior, and decline in social performances. In terms of neuropathology, the morphological hallmarks of the disease are the accumulation of alpha–beta peptide and the neurofibrillary degeneration, associated with synaptic alterations, involving mostly the dendritic spines. This study is based on the morphological analysis of 10 brains, 5 of which were obtained from patients who suffered from Alzheimers disease and 5 from nondemented senile individuals used as control group. The segments taken in major from the occipital lobe were studied with the use of Golgi method, as well as Gallyas’ and Bielschowski’ s staining methods. In most of the pyramidal cells in the affected brains, there seems to be important spine loss and extensive dendrite pathology. Apical dendrites are distorted and tortuous. Horizontal dendritic arborization is severely decreased leading to an amputated, bell-shaped cell soma. Senile plaques have been often revealed, and neurofibrillary changes have also been noticed.

Pupil Light Reflex in Parkinson's Disease: Evaluation With Pupillometry

ABSTRACT We evaluated pupil light reflex (PLR) in patients with Parkinsons disease (PD) and normal controls by means of pupillometry and explored its possible relation to clinical characteristics in parkinsonian patients. PLR was evaluated using pupillometry in 66 patients with PD without clinical evidence of autonomic dysfunction and 44 healthy matched controls. PLR was elicited by single flash stimuli of 24.6 candelas/m2 intensity and 20 ms duration, and six parameters were studied after full recording of pupils movement. A significant increase in latency (T1) and significant decrease in amplitude (R1–R2), maximum constriction velocity (Vmax), as well as maximum acceleration (ACmax) was found in parkinsonian patients. There was no significant difference in initial radius (R1) and minimum radius (R2) values. Of the parameters studied, ACmax emerged as a significant predictor for discrimination between PD patients and controls. There was no significant correlation between pupillometry parameters and clinical characteristic of patients (disease duration, stage, and the Unified Parkinsons Disease Rating motor scale). The study demonstrates PLR disorder in PD patients even without overt clinical autonomic dysfunction. Pupillometry appears to be a useful and noninvasive method for exploration of PLR alterations in PD and may prove to be useful for the early detection of subclinical autonomic nervous system dysfunction.

Pupillometry and 123I-DaTSCAN imaging in Parkinson's Disease: A Comparison Study

ABSTRACT The purpose of this study was the evaluation of pupil light reflex (PLR) in patients with Parkinsons disease (PD) by using a modern pupillometry system and the investigation of its potential relationship with dopamine transporter imaging (DaTSCAN), which is an objective method for the evaluation of presynaptic dopaminergic system. PLR was evaluated using pupillometry in 35 patients with PD without clinical evidence of autonomic dysfunction and 44 healthy matched controls. PLR was elicited using a fully automated pupillometry system and six parameters were measured. Dopamine transporter imaging was performed using radioactive ioflupane 123I-FP-CIT [123I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)-nortropane]. A significant increase in latency and a significant decrease in amplitude, maximum constriction velocity, as well as maximum acceleration were observed in PD patients. There was no significant difference in initial radius and minimum radius values. Investigating the relationship between pupillometry parameters and 123I-FP-CIT binding values, we correlated values from the semiquantitative analysis of radioligand uptake with pupillometry parameters, but we found no significant correlation. This study demonstrates PLR impairment in patients with PD without overt autonomic dysfunction. This impairment does not seem to correspond to the reduction of radioligand binding in the striatum as the result of presynaptic dopaminergic dysfunction, suggesting a different deterioration rate of these systems.

Pupillometric characteristics in patients with choroidal neovascularization due to age-related macular degeneration

Purpose To study the pupillary light reflex in patients with choroidal neovascularization due to age-related macular degeneration (AMD). Methods The study included 15 patients with AMD and 15 control subjects. A full recording of the pupils reaction to light was registered and the following eight parameters were measured and reported: baseline pupil radius (R1), latency (T1), minimum pupil radius (R2), amplitude (AMP), maximum constriction velocity (VCmax), maximum constriction acceleration (AC-max), time for maximum velocity (T2), and time for maximum constriction (T3). Results All variables measured presented alterations in the AMD group and a number of them were significantly reduced in the AMD group. Conclusions The presence of neovascular AMD significantly affects the pupils response to light stimulus when compared to normal subjects.

Pupillometry and MRI findings of hippocampus in Alzheimer's disease

Background Alzheimers Disease (AD) is the leading cause of dementia, accounting for 70% of all dementias in old age. In clinical practice the diagnosis is based on typical features of the disease and exclusion of other conditions causing dementia or cognitive dysfunction. So far the diagnosis of definite AD can be confirmed only by brain biopsy or at autopsy. Therefore, a reliable noninvasive diagnostic method is mainly needed at this stage. In recent years, scientists based on the cholinergic hypothesis of the Alzheimers disease1 developed systems of recording and measuring the pupil size (pupillometry) finding out that the pupil light reflex (PLR) responded in a particular way in Alzheimers disease patients. Today imaging methods are an integral part of the diagnostic work-up of patients with suspected dementia. MRI provides data of in vivo tissue and enables evaluation of brain structures such as the hippocampus.

Pupillometry in depressed patients

Background The multiple applications of pupillometry in different diseases are based on the direct relation of autonomic nervous system and its neurotransmitters (Acetylcholine and Norepinephrine) to miosis and mydriasis of the pupil. The sphincter muscle of the iris leads to miosis (neurotransmitter – Acetylcholine), while the dilator muscle leads to mydriasis (neurotransmitter – Norepinephrine).

Myasthenia gravis: a pupillometric study

Myasthenia gravis (MG) is a disease of the neuromuscularjunction (NMJ) that, in its typical form, is caused byautoimmune on the postsynaptic receptors of Acetylcho-line (AChRs) of the Peripheral Nervous System (PNS)1.We investigate the effect of MG on the Central NervousSystem (CNS) and the pupillary smooth muscle.

Relation of pupillary light reflex to light intensity

Materials and methods The pupillary recording system used is computer controlled, includes an infrared digital video camera capable of recording 260 frames/sec (260 Hz) and it provides real time measurements, online full statistical analysis of the results and averaging of the important parameters. Pupil reactions of twenty normal healthy volunteers aged 20 to 28 were measured for 7 light intensity levels of the flash. Stimulus parameters were flash light wavelength 555 nm, retinal illuminance intensity-1230 trolands, 150 trolands, 100 trolands, 25 trolands, 6.4 trolands, 1.6 trolands and 0.1 trolands – stimulus time 10 ns, background retinal illumination 0 trolands and interstimulus interval 3s. Pupillometric parameters studied were reaction time, initial Radius, minimum Radius, min/initial Radius [%], final/initial Radius [%], time for maximum myosis, maximum velocity and maximum acceleration.