Israel Medical Association Journal

A 47 year old man presented with a combination of dry mouth and lightheadedness while standing. His medical background was unremarkable except for cigarette smoking and hyperlipidemia. Sjögren’s syndrome was ruled out, and he was referred for evaluation of orthostatic hypotension, which by then included syncopal episodes and injuries. Additional symptoms included dry eyes, constipation, reduced sweating, and erectile dysfunction. After excluding medications and structural cardiac abnormalities as causes of orthostatic hypotension, a clinical autonomic evaluation was performed. The pattern of beat-to-beat blood pressure associated with performance of the Valsalva maneuver, and a low plasma norepinephrine level that did not increase in response to standing, established that the orthostatic hypotension was neurogenic. Treatment with an alpha-adrenoceptor agonist and fludrocortisone yielded partial improvement. After systemic diseases involving autonomic failure were excluded, cardiac sympathetic neuroimaging was performed by ¹²³I-metaliodobenzylguanidine (MIBG) scanning. The normal uptake seen in the heart indicated intact post ganglionic sympathetic innervation. There were no signs of central neurodegeneration or peripheral neuropathy. Because of symptoms and signs of both parasympathetic and sympathetic failure without denervation, an autonomic ganglionopathy was considered. A high titer of antibody to the neuronal nicotinic receptor, which mediates ganglionic neurotransmission, was obtained. The diagnosis of autoimmune autonomic ganglionopathy (AAG) was made, and the management strategy shifted to first lowering the antibody burden by plasma exchanges and then instituting chronic anti-autoimmune treatment with rituximab and a low dose of cortiosteroid. The patient showed remarkable improvement.

Background: Vascular insufficiency is considered to play an important role in the pathogenesis of normal-tension glaucoma (NTG). Autoregulation of blood flow in the eye has been shown to be impaired in NTG, resulting in the inability to compensate for changes in intraocular pressure or blood pressure in order to maintain adequate perfusion. Objectives: To evaluate the occurrence of combined bradycardia-hypotension during 24 hour monitoring of blood pressure and heart rate in patients with NTG.

Methods: Eleven NTG patients participated in the study. All had episodic symptoms of dizziness or lightheadedness, but were confirmed as not having a diagnosis of orthostatic hypotension. Twenty-four hour monitoring was performed with systemic blood pressure and heart rate automatically measured every 20 minutes during daytime and every hour during the night. The cardiac diastolic and systolic double products (dDP and sDP) at each reading were calculated by multiplying the heart rate by the respective blood pressure. dDP < 3600 and sDP < 5400 (corresponding to a heart rate of 60 beats/min and a blood pressure of 60 and 90 mmHg, respectively) were considered abnormally low, and dDP < 2500 and sDP < 4000 (corresponding to a heart rate 50 beats/min and a blood pressure of 50 and 80 mmHg, respectively) were considered severely abnormal.

Results: dDP was abnormally low in all 11 NTG patients on at least one occasion, the majority occurring during the night-time hours, while abnormally low sDP was present in 8 of the 11 patients. The mean cumulative duration of low dDP readings was 4.2 ± 3.2 hours. Severely low dDP readings were observed in six patients.

Conclusions: Abnormally low dDP was recorded in all NTG patients, lasting more than an hour in the majority of cases. Abnormally decreased dDP may represent a state of cardiovascular autonomic dysregulation, resulting in low ocular perfusion in certain NTG patients.