Cardiovascular reflex tests detect autonomic dysfunction in symptomatic and pre-symptomatic subjects with hereditary transthyretin amyloidosis.

PURPOSE: Autonomic dysfunction is a distinctive but undervalued feature of hereditary transthyretin amyloidosis (ATTRv). It may predate the onset of polyneuropathy and cardiomyopathy, thereby providing crucial prognostic and therapeutic information. The objective of this study was to assess autonomic function by means of the standardized cardiovascular autonomic reflex tests (CRTs) in a cohort of subjects with genetically proven ATTRv from non-endemic areas who were in the symptomatic and pre-symptomatic stages. METHODS: All subjects enrolled in this cross-sectional study had genetically proven ATTRv. They underwent the head-up tilt test, Valsalva manoeuvre, deep breathing test, cold face test and handgrip test while under continuous blood pressure and heart rate monitoring. Based on the results of the nerve conduction study, the subjects were divided into two groups: those with polyneuropathy (ATTRv-wPN) and those without polyneuropathy (ATTRv-woPN). Age- and sex-matched healthy controls (HC) were used for comparison. RESULTS: Thirty-seven ATTRv subjects (19 with ATTRv-wPN, 18 with ATTRv-woPN) and 41 HC performed the CRTs. Of these 37 subjects with ATTRv, four (11%) presented neurogenic orthostatic hypotension the during head-up tilt test. Based on the results of the CRTs, autonomic dysfunction characterized by either sympathetic or parasympathetic impairment was detected in 37% and 63% of ATTRv-wPN subjects, respectively. Subjects with ATTRv-woPN presented a significant impairment of autonomic responses to the Valsalva manoeuvre compared to the HC (overshoot p = 0.004; Valsalva ratio p = 0.001). CONCLUSION: Autonomic dysfunctions are frequent in subjects with ATTRv when investigated by means of standardized CRTs, and are also relevant in the pre-symptomatic stage. Cardiovagal functions are the primary functions affected, among others. This may be crucial in defining the proper diagnostic workout for early diagnosis and improving the likelihood of providing the patient with prompt administration of disease-modifying treatments.

A new integrated instrumental approach to autonomic nervous system assessment.

BACKGROUND AND OBJECTIVES: The autonomic nervous system (ANS) regulates involuntary body functions and is commonly evaluated by measuring reflex responses of systolic and diastolic blood pressure (BP) and heart rate (HR) to physiological and pharmacological stimuli. However, BP and HR values may not sufficient be to explain specific ANS events and other parameters like the electrocardiogram (ECG), BP waves, the respiratory rate and the electroencephalogram (EEG) are mandatory. Although ANS behaviour and its response to stimuli are well-known, their clinical evaluation is often based on individual medical training and experience. As a result, ANS laboratories have been customized, making it impossible to standardize procedures and share results with colleagues. The aim of our study was to build a powerful versatile instrument easy-to-use in clinical practice to standardize procedures and allow a cross-analysis of all the parameters of interest for ANS evaluation. METHODS: The new ANScovery System developed by neurologists and technicians is a two-step device: (1) integrating physiological information from different already existing commercial modules, making it possible to cross-analyse, store and share data; (2) standardizing procedures by an innovative tutor monitor able to guide the patient throughout ANS testing. RESULTS AND CONCLUSIONS: The daily use of the new ANScovery System in clinical practice has proved it is a versatile easy to use instrument. Standardization of the manoeuvres and step-by-step guidance throughout the procedure avoid repetitions and allow intra and inter-patient data comparison.

Switching on the deep brain stimulation: effects on cardiovascular regulation and respiration.

BACKGROUND: Objective of this study was to evaluate the acute cardiovascular and respiratory effects of switching on the deep brain stimulation in the follow up of nine Parkinson's disease patients with subthalamic nucleus stimulation and six cluster headache patients with posterior hypothalamic area stimulation. METHODS: Systolic and diastolic blood pressure, heart rate, and respiratory rate were monitored continuously during supine rest in both groups. Each patient was assessed in two conditions: resting supine with stimulator off and with stimulator on. RESULTS: In supine resting condition switching on the DBS induced no significant changes (p>0.05) in systolic and diastolic blood pressure as well as in heart rate and respiratory rate, in both groups of patients, either taking 1 min or 10 heartbeats as a sample for analysis. CONCLUSIONS: Switching on the DBS does not modify heart rate, blood pressure nor respiratory rate in both Parkinson and cluster headache patients under resting conditions.

Standing worsens cognitive functions in patients with neurogenic orthostatic hypotension.

In previous studies, addressing the association between orthostatic hypotension and cognitive decline, patients underwent neuropsychological evaluation in sitting position, and blood pressure values and cognition were not measured concurrently. Furthermore, no studies assessed the acute effects of orthostatic hypotension on cognitive performances. The aim of our study was to evaluate the effect of a documented fall in systolic blood pressure (SBP) of at least 20 mmHg on a battery of cognitive tests in patients with neurogenic orthostatic hypotension. Ten consecutive patients with neurogenic orthostatic hypotension, normal brain imaging, and a normal Mini Mental State Examination in supine position were enrolled in the study. Patients underwent a detailed neuropsychological assessment (Brief Mental Deterioration battery and computerized tests) over two test sessions: the first while tilted to an angle able to cause a fall of at least 20 mmHg in SBP; the second while supine, after 30 min of rest. Parallel forms of the tests were presented on each testing session. Patients scored significantly worse in the visual search test, analogies test, immediate visual memory, and the measure of global cognitive functioning of Brief Mental Deterioration battery during the orthostatic challenge compared to the supine position. Orthostatic hypotension was associated with a significant worsening of cognitive performances, affecting both global cognitive functioning and specific tasks, mainly exploring executive functions. The assessment of cognitive function in patients with neurogenic orthostatic hypotension should be performed considering the body's position of the subject.

Progression of cardiovascular autonomic dysfunction in Holmes-Adie syndrome.

The Holmes-Adie Syndrome (HAS) is a disorder of unknown aetiology comprising unilateral or bilateral tonic pupils with near light dissociation and tendon areflexia. Although considered to be benign, troublesome symptoms may result from autonomic disturbances, affecting vasomotor, sudomotor and respiratory function. It is unclear if the autonomic manifestations of the disease remain stable or progress, as longitudinal studies with detailed autonomic assessments have not been described. The authors report four HAS patients studied at intervals over 16, 8, 4 and 2 years with cardiovascular autonomic tests (head-up tilt, isometric exercise, mental arithmetic, cutaneous cold, deep breathing, Valsalva manoeuvre and standing). In each, there was progression of cardiovascular autonomic deficits with time, accompanied by symptomatic worsening. These observations in HAS, for the first time, indicate progression of cardiovascular autonomic dysfunction of clinical significance. This has a number of implications, including those relating to aetiology and prognosis. The authors recommend regular clinical and laboratory follow-up, especially of cardiovascular autonomic function, in patients with HAS.

Effect of deep brain stimulation of the posterior hypothalamic area on the cardiovascular system in chronic cluster headache patients.

The objective of this study was to determine the cardiovascular effects of chronic stimulation of the posterior hypothalamic area (PHA) in cluster headache (CH) patients. Systolic and diastolic blood pressure (SBP, DBP), cardiac output, total peripheral resistance (TPR), heart rate (HR) and breathing were monitored at supine rest and during head-up tilt test (HUTT), Valsalva manoeuvre, deep breathing, cold face test and isometric handgrip in eight drug-resistant chronic CH patients who underwent monolateral electrode implantation in the PHA for therapeutic purposes. Autoregressive power spectral analysis (PSA) of HR variability (HRV) was calculated at rest and during HUTT. Each subject was studied before surgery (condition A) and after chronic deep brain stimulation (DBS) of PHA (condition B). Baseline SBP, DBP, HR and cardiovascular reflexes were normal and similar in both conditions. With respect to condition A, DBP, TPR and the LF/HF obtained from the PSA of HRV were significantly (P < 0.05) increased during HUTT in condition B. In conclusion, chronic DBS of the PHA in chronic CH patients is associated with an enhanced sympathoexcitatory drive on the cardiovascular system during HUTT.

Headache and hypertension.

Headache is generally regarded as a symptom of high blood pressure in spite of conflicting opinions on the association of headache and arterial hypertension. Most studies have shown that mild chronic hypertension and headache are not associated and this demonstration needs to be implemented in clinical practice. Whether moderate hypertension predisposes to headache remains controversial, but there is little evidence that it does. Headaches caused by significant disturbances in arterial pressure are included in the section "Headache attributed to a disorders of homeostasis" (code 10.3) of the 2nd edition of the International Classification of Headache disorders.