Dimitrios Tsiptsios

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.

Familial case of speech-induced tongue-protrusion dystonia

Lingual dystonia is a rare type of focal dystonia. In clinical practice, it is typically observed in tardive dystonias or other secondary/heredo-degenerative dystonias in disorders such as neuroacanthocytosis, pantothenate kinase-associated neurodegenerations, neuroferritinopathy, or Wilson’s disease. Primary lingual dystonia induced by speaking is usually idiopathic in origin and is characterized by increased tonus of the tongue, which causes protrusion only during speaking. We present a familial form of dystonia in 2 siblings, in which speech-induced primary lingual dystonia remained the only clinical feature for many years until it slowly progressed to multifocal dystonia. Potential genetic susceptibility factors for primary focal dystonia were investigated.

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.

Helicobacter pylori may be involved in stroke pathophysiology by altering tumor necrosis factor-α and matrix metalloproteinases

Dear Editor, We read with considerable interest the paper by Munshi A et al. [1] concluding that tumor necrosis factor (TNF)-a + 488 G/A variant but not matrix metalloproteinase (MMP)-3 1612 5A/6A polymorphism is an important risk factor for ischemic stroke in South Indians. However, the authors did not mention the role of environmental agents involved in the TNF-a/MMPs-induced pathophysiology of stroke. In this regard, systemic inflammatory events, such as infections, increase the risk of stroke, are associated with worse outcome, and the mediators of this clinically important effect may include cytokines such as TNF-a and MMP involved in the blood–brain barrier (BBB) disruption; BBB dysfunction is a hallmark of many central nervous system pathologies including ischemic stroke [2] and can lead to an increase in vascular permeability and brain edema, exacerbating the ischemic injury. Specifically, Helicobacter pylori infection (Hp-I), a well-recognized cause of upper gastrointestinal pathologies affecting 85% of South Indian population [3], is a risk factor for ischemic stroke [4]; Hp is present in carotid atherosclerotic lesions associated with features of inflammatory cell response, CagA-positive strains of Hp are significantly associated with atherosclerotic stroke and its recurrence, and Hp strains induce platelet aggregation, leading to thrombosis events. Hp-I, by releasing several of the aforementioned inflammatory mediators, could induce BBB breakdown, thereby being involved in the pathogenesis of neuropathies including stroke [4,5]. For instance, Hp could indirectly affect the peripheral and central nervous systems through the release of numerous cytokines such as TNF-a acting at distance; TNF-a is involved in BBB disruption through MMP upregulation [5]. Moreover, Hp-induced vacuolating cytotoxin A exhibits chemotactic activities to the bone marrowderived mast cells (BMD-MCs) and induces BMD-MCs to produce proinflammatory cytokines involved in the BBB disruption [5]. It would thus be interesting to know if the authors have considered the aforementioned data regarding the consideration that Hpinduced TNF-a and MMP might be involved in stroke development, through an impaired BBB, in their South Indian participants, expected to exhibit a possible high prevalence of Hp-I. If a role of Hp-I in the stroke pathophysiology is demonstrated, this might have a major impact on the management of this disease.

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.

Pupillometric evaluation of patients suffering from age related macular degeneration (AMD): a comparative study with electrophysiological and optical methods

Materials and methods A total of ten subjects were included in this study: five patients with age-related macular degeneration (AMD) and five subjects with healthy eyes matching sex and age. Patients with AMD had stage 4 exudative AMD with presence of a choroidal neovascular membrane at the macular region. Mean and standard deviations of the pupil size, minimum/initial radius (%), final/initial radius (%) and maximum acceleration were calculated using the students T-test for both control subjects and patients.

Pupillometry and neuroimaging methods in patients with Parkinson's disease

Background The diagnosis of Parkinsons disease is based on clinical criteria. There is no specific examination for the ascertainment of the diagnosis of Parkinsons disease. Therefore, its very important to find more objective markers for a certain diagnosis especially at initial stages of the disease. Pupillometry, a non-invasive method, which examines pupil reaction to light and analyses its movement, may be of special scientific interest as far as diagnosis of Parkinsons disease is concerned.