Correlation of Dopaminergic Denervation and the Progression of Autonomic Dysfunctions in Different Clinical Subtypes of Parkinson’s Disease

Background. Autonomic dysfunctions occur in the early stage of Parkinson’s disease (PD) and impact the quality of life during the progression of the disease. In this study, we evaluated the serial progression of autonomic dysfunctions between different subtypes of a prospective PD cohort. Materials and Methods. From the Parkinson’s Progression Markers Initiative (PPMI) database, 325 PD patients (age: 61.2 ± 9.7, M : F = 215 : 110) were enrolled. Patients were subgrouped into tremor-dominant (TD), indeterminate, and postural instability and gait disorder (PIGD) subtypes. The progression of autonomic dysfunctions and dopaminergic denervation from I-123 FP-CIT SPECT images of each group were analyzed and compared at baseline, 12 months, 24 months, and 48 months of follow-up periods. Results. The SCOPA-AUT score of the indeterminate subtype was significantly higher than that of the TD subtype ( P < 0.05 ) at baseline and was significantly higher than that of both TD and PIGD subtypes ( P < 0.05 ) at 48 months. The indeterminate subtype had the most significant correlation between the aggravation of dopaminergic denervation in I-123 FP-CIT SPECT images and the increase of SCOPA-AUT scores during 48 months of follow-up (r = 0.56, P < 0.01 ). Conclusions. Autonomic dysfunctions were most severe in the indeterminate subtype throughout the 48 months of the follow-up period, with a significant correlation with dopaminergic denervation. We suggest a positive relationship between dopaminergic denervation and autonomic dysfunctions of the indeterminate subtype, beginning from the early stage of PD.

P.088 Dysautonomia and Diabetes: A Prodrome to Fatal Familial Insomnia (FFI)

Background: Fatal Familial Insomnia (FFI) is an autosomal dominant multisystem prion disease, with sleep disorders often being the first presentation. Although autonomic dysfunctions are key features, the frequency and timing vary between reports, and may accompany early insomnia. Moreover, endocrine changes are reported, but diabetes rarely is - with unclear timing of onset in relation to the insomnia. Methods: N/A Results: Here we present a 46-year-old previously healthy male, who within 22 months prior to the onset of sleep disturbances, developed hypertension and diabetes. Then within 3-4 months after onset of sleep disturbances development tachycardia and diaphoresis. His sleep continued to deteriorate, and later developed bulbar impairment, ataxia, diplopia, sleep apnea and cognitive decline. He passed away 20 months from onset of insomnia. Polysomnography showed status dissociates and central apnea. He had positive genetic testing, PRNP c.532G>A (p.Asp178Asn) and PRNP c.385A>G (pMet129Val), a pathological confirmation, and a positive family history Conclusions: Here diabetes and hypertension significantly preceded sleep disturbances, and tachycardia and diaphoresis developed shortly after. This illustrates that dysautonomia and endocrine dysfunction may be unrecognized prodromes in some cases of FFI, and could be an early marker of clinical disease onset and therapeutic interventions, especially in genetically confirmed asymptotic patients.

A case of cranial autonomic dysfunctions predominant migraine: Migraine sans ache

Pain is the essential part of migraine headaches along with other features, whereas, cranial autonomic symptoms (CAS)/signs are a predominant and essential part of trigeminal autonomic cephalalgias. What if other features of migraine are present but the pain is absent? One such variation in migraine symptomatology is reported in this case, where the pain was not there but CAS/signs were predominant along with other features of migraine. The possible mechanism for such variation, in this case, maybe desensitization of afferent loop (comprised by nociceptors in extracranial and intracranial pain-sensitive structures supplied by the trigeminal nerve) and direct activation of the trigemino-cervical complex and brainstem structures causing dissociation of pain from the rest of the features of migraine. In this case, as the pain part gets completely dissociated from CAS/signs, hence this condition can be termed as “migraine sans ache.” The patient was started on anti-migraine treatment and she responded wonderfully

Indicators of the External Respiratory System and Cardiac Activity in Adolescents with Vegetative Dysfunctions, Depending on Gender and Presence of Perinatal Pathology

This work is based on the results of clinical and functional studies of the cardiovascular and respiratory systems in adolescents with ADS, depending on the presence of perinatal pathology. In order to identify the features of the state of the respiratory system and cardiac activity in children with autonomic dysfunctions, depending on gender. We examined 243 adolescents 12-18 years old with clinically and laboratory-instrumental confirmed dysfunction of the autonomic nervous system - autonomic dystonia syndrome. It was found that signs of cardiac dysfunction are more often observed in adolescents with ADS with a history of perinatal pathology, mostly in males. The risk of developing violations of bronchial patency was identified in adolescents with ADS with a history of perinatal pathology, to a greater extent in females.

Pathophysiological mechanisms that alter the autonomic brain-liver communication in metabolic diseases

The brain influences liver metabolism through many neuroendocrine and autonomic mechanisms that have evolved to protect the organism against starvation and hypoglycemia. Unfortunately, what is normally an effective way to prevent death has become dysregulated in modern obesogenic environments, but the pathophysiological mechanisms behind metabolic dyshomeostasis are still unclear. In this Mini-Review, we provide our thoughts regarding obesity and type 2 diabetes as diseases of the autonomic nervous system. We discuss the pathophysiological mechanisms that alter the autonomic brain-liver communication in these diseases, and how they could represent important targets to prevent or treat metabolic dysfunctions. We discuss how sympathetic hyperactivity to the liver may represent an early event in the progression of metabolic diseases and could progressively lead to hepatic neuropathy. We hope that this discussion will inspire and help framing a model on the importance of better understanding the chronology of autonomic dysfunctions in the liver in order to apply the right strategy at the right time.

Pure Autonomic Failure: A Case Report of Recurrent Orthostatic Hypotension

Pure autonomic failure is a neurodegenerative disorder affecting the autonomic nervous system which clinically presents with orthostatic hypotension. It is a diagnosis of exclusion after detailed clinical examinations and relevant investigations. Here, we discuss a case of 68 years old male who had complaints of multiple episodes of loss of consciousness on standing from a sitting position for the last 3 years. The diagnosis was considered by clinical examinations revealing autonomic dysfunctions with normal appropriate investigations. The patient was treated successfully with midodrine, fludrocortisone, and other non-pharmacological interventions. We focused on doing various autonomic dysfunction tests in the evaluation of a patient with recurrent orthostatic hypotension. We suspect that pure autonomic failure might not have been considered in the differential diagnosis of recurrent orthostatic hypotension and suggest that it is to be kept as a differential in such a scenario. Midodrine has an effective role in syncope due to sympathetic vasoconstrictor failure.

Heart Matters: Cardiac Dysfunction and Other Autonomic Changes in Parkinson’s Disease

It has been more than 200 years since James Parkinson made the first descriptions of the disease that bears his name. Since then, knowledge about Parkinson’s disease has been improved, and its pathophysiology, diagnosis, and treatments are well described in the scientific and medical literature. However, there is no way to prevent the disease from its progressive nature yet and only its symptoms can be minimized. It is known that the process of neurodegeneration begins before the onset of motor signs and symptoms of the disease, when diagnosis is usually made. Therefore, recognizing manifested non-motor symptoms can make an early diagnosis possible and lead to a better understanding of the disease. Autonomic dysfunctions are important non-motor manifestations of Parkinson’s disease and affect the majority of patients. Importantly, heart failure is the third leading cause of death in people suffering from Parkinson’s disease. Several evidences have shown the correlation between Parkinson’s disease and the preexistence of cardiovascular diseases. Therefore, cardiovascular monitoring and identification of its dysfunctions can have a prodromal role for Parkinson’s disease. This review presents studies of the literature that can lead to a better understanding of Parkinson’s disease with special attention to its relation to heart and cardiovascular parameters.