Cardiovascular and sweating dysfunction in patients with Holmes-Adie syndrome.

A cross-sectional study is reported in which 53 patients with Holmes-Adie syndrome have been subjected to a battery of tests of autonomic nervous function referable to the cardiovascular system, to two objective tests of sweating function, and to subjective assessment of sweating by application of quinizarin powder followed by body heating. The majority of patients were consecutive referrals; none was selected because of clinical indications of autonomic dysfunction. Eighty three per cent of these patients had at least one, 57% at least two, and 40% at least three objective test abnormalities, as defined by values lying outside 95 percentiles of healthy subjects who were matched for age and subjected to the same tests. In the context of multiple testing, the probability of finding outside values was such that a minimum of 3 was required to define abnormality. On this basis 40% of patients were found to have significant evidence of autonomic dysfunction. The most frequent abnormalities were impaired digital vasoconstriction to cold (23%), a reduced heart rate response to the Valsalva manoeuvre (17%), and excessive variability in sweating between test sites (in one of the tests, 43%) which is consistent with patchy loss. Abnormal quinizarin test appearances were seen in 10 patients and in a further five patients the appearances were thought to be suggestive of abnormality. Though assessment of the results of this test are subjective, the observations are consistent with the findings obtained from the objective tests which were applied. Cardiovascular and sweating abnormality did not concur significantly and only the former was found to increase progressively with known duration of the pupillotonia. It is concluded that Holmes-Adie syndrome is commonly accompanied by progressive mild but widespread autonomic involvement but rarely is this symptomatic. If symptoms suggestive of autonomic neuropathy are found in a patient with tonic pupils, a careful search for some other generalised disorder is recommended.     

Tonic vibration reflex in Holmes-Adie syndrome: an electrophysiological study

The pathophysiological mechanisms underlying benign areflexia were studied in six patients with Holmes-Adie syndrome. No impairment of sensory conduction velocity of sural nerve was found. A normal tonic vibration reflex was obtained in all patients. H reflex was absent in five patients, but responses like F waves were recorded in three subjects. These findings suggest that muscle spindles are not affected and that spinal motoneurone excitability is normal.     

A hypothetical immunemediated unifying mechanism for the Holmes-Adie syndrome

The Holmes-Adie syndrome consists of pupillotonia, arreflexia and autonomic dysfunction. Some explanations for these different symptoms have been attempted, centred upon neuropathological and electrophysiological findings. A hypothetical immunemediated mechanism, as in the Guillain Barré syndrome, is presented in this paper for explaining the three chief symptoms of the syndrome.     

Orthostatic hypotension in patients with Alzheimer’s disease: a meta-analysis of prospective studies

Neurological Sciences - Orthostatic hypotension (OH) is a clinical sign associated with severe adverse health outcomes in older adults. It has been reported to be common in patients with...     

Orthostatic dyspnea: a neglected symptom of orthostatic hypotension

Dyspnea is a common symptom in patients with pulmonary and cardiac disease. Orthostatic hypotension is rarely considered a cause of dyspnea. We reviewed the medical records of 651 consecutive patients referred for the evaluation of dysautonomia to investigate the prevalence of dyspnea and its association with OH and other autonomic abnormalities. Dyspnea was reported by questionnaire in 30% of patients with OH, compared to 10% of age and sex matched patients without OH (P<0.05, chi(2)). There was a trend toward earlier blood pressure falls in patients with dyspnea. During autonomic testing, 25% of patients (10 of 40) with OH who reported dyspnea on the questionnaire had shortness of breath coincident with blood pressure falls during tilt table and active standing. The time to maximal blood pressure fall was shorter in patients with OH who experienced shortness of breath during testing compared to those without dyspnea (11 minutes vs. 21 minutes, P<0.05). In this study, dyspnea was frequently associated with OH. Ventilation perfusion mismatch, due to inadequate perfusion of ventilated lung apices may be the most likely underlying cause of orthostatic dyspnea in patients with OH.     

Orthostatic hypotension associated with an epidermoid tumor of the IV ventricle

We report the case of a 32-year-old man with an epidermoid tumor of the fourth ventricle. About 14 years later, he showed a tumor recurrence which was removed. After this procedure the patient complained of presyncopal and syncopal crisis while attempting to stand or walk. On examination, severe orthostatic hypotension was confirmed and autonomic tests were abnormal. The brain MRI showed a tetraventricular hydrocephalus predominating in the fourth ventricle. A ventriculo-peritoneal shunt was performed, and after surgery the orthostatic intolerance improved. We believe that hydrocephalus has probably been a contributory factor to orthostatic hypotension, and suggest expanding testing for dysautonomia in patients with hydrocephalus.     

Orthostatic hypotension in familial amyloid polyneuropathy: treatment with DL-threo-3,4-dihydroxyphenylserine

We measured plasma norepinephrine levels in patients with familial amyloid polyneuropathy. Patients with orthostatic hypotension had low basal plasma norepinephrine levels, which did not increase after postural change. On the basis of biochemical findings that suggest depletion of peripheral norepinephrine, DL-threo-3,4-dihydroxyphenylserine, an immediate precursor of norepinephrine, was given orally. Six hundred mg of this drug induced substantial and sustained elevation of blood pressure for several hours, and plasma norepinephrine content increased. Daily administration for 4 weeks improved postural dizziness and syncope, and daily activity increased.     

Orthostatic tremor: report of two cases and an electrophysiological study

Two patients with legs tremor present on standing, but none on walking or sitting, are reported. Tremor was not exclusive or orthostatism and was also evoked by strong tonic contraction of leg muscles. Synchronous EMG bursts were recorded in antagonistic muscle groups at 8-10 Hz in the first patient and at 16 Hz in the second. EMG activity was synchronous in corresponding muscles of both legs. The occurrence of EMG activity was not influenced by stimulation of nerve afferent fibers. We suggest that this movement disorder may be an exaggeration of physiological tremor due to synchronization of motor units by spontaneous oscillations in central structures.     

A case of bilateral tonic pupil (Holmes-Adie syndrome)

The authors present a case of bilateral tonic pupil and discuss clinical and physiopathological aspects of this syndrome. They discuss some elements necessary for the understanding of the etiopathogenesis of the disease.     

Orthostatic hypotension in patients with late‐life depression: Prevalence and validation of a new screening tool

Objectives

The objective of this study was to assess the prevalence of orthostatic hypotension (OH) in a sample of late life depression (LLD) patients and to determine the validity of a standardized questionnaire, the Orthostatic Hypotension Questionnaire (OHQ). Secondarily, we wished to assess variables associated with OH.

Methods

We conducted a cross‐sectional study on 82 consecutive geriatric outpatients presenting with LLD. OH was defined as a fall in systolic blood pressure of greater than 20 mm Hg and/or 10 mm Hg on diastolic blood pressure on an orthostatic stress test from sitting to standing. Logistic regressions were used to identify factors associated with OH.

Results

The prevalence of OH as measured on the orthostatic stress test and on the OHQ was 28% and 57%, respectively. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of the OHQ were 69.6% (95% CI 47%‐87%), 47.5% (95%CI 34%‐61%), 0.54 (95% CI: 0.43‐0.64), 34% (95%CI 21%‐49%), and 80% (95%CI 63%‐92%), respectively. Females were more likely to have OH (OR: 3.96, 95%CI 1.06‐14.89, P = .041), and those married or in a common‐law relationship were less likely to have OH (OR: 0.25, 95% CI 0.08‐0.72, P = .011).

Conclusions

OH is common in patients with LLD conferring them a risk of gait instability and falls. Females had a higher risk of having OH while participants who were married or in a common‐law relationship were less likely to have OH. Although the OHQ is a quick to administer paper‐based screening test, it did not show adequate diagnostic accuracy in patients with LLD seen in a routine psychiatry clinic.     

Chronic cough in the Holmes-Adie syndrome: association in five cases with autonomic dysfunction

The Holmes-Adie syndrome consists of unilateral or bilateraltonic pupils with near light dissociation and tendon areflexia. It isassociated with autonomic disturbances affecting sudomotor andvasomotor function. Five such patients are reported on who also had atroublesome chronic dry cough, which was of unknown aetiology and wasresistant to a range of treatments. The cough may be related toinvolvement of afferent or efferent pathways in the vagus. Chroniccough may be an accompaniment in the Holmes-Adie syndrome, like otherforms of autonomic dysfunction.

     

Ross syndrome plus: beyond horner, Holmes-Adie, and harlequin

BACKGROUND: Ross syndrome is an uncommon disorder characterized by the triad of segmental anhidrosis, hyporeflexia, and tonic pupils. METHODS: The authors describe the clinical findings of five patients with Ross syndrome and detail the results of their pharmacologic and autonomic testing. RESULTS: In four patients, the classic findings of Ross syndrome were accompanied by Horner's syndrome. Other symptoms of dysautonomia were also common. CONCLUSIONS: These findings suggest that Ross syndrome is a dysautonomic condition of varying expression resulting from a generalized injury to ganglion cells or their projections.     

Pituitary enlargement in patients with intracranial hypotension syndrome

Article abstract-The authors analyzed whether the pituitary gland enlarges in intracranial hypotension syndrome by studying 11 consecutive patients. Initial MRI scans showed pituitary gland enlargement with a convex superior margin. Follow-up MRI studies revealed that the size of the gland invariably diminished in all patients. The authors hypothesize that pituitary gland enlargement in intracranial hypotension syndrome is due to hyperemia of dural and epidural venous sinuses.     

On the cause of hyporeflexia in the Holmes-Adie syndrome

Electrophysiologic studies were carried out on 11 patients with Holmes-Adie syndrome, 8 of whom had reduced or absent ankle jerks. Conduction velocities and evoked nerve and muscle compound action potentials in the peroneal, posterior tibial, and sural nerves were normal. The H reflex was absent (or virtually absent) in the patients with depressed reflexes. The amplitude of the composite Ia EPSP in single soleus motoneurons was estimated from changes in firing probability of voluntarily activated soleus motor units in response to stimulation of low threshold afferents in the tibial nerve. These amplitudes were used to test the afferent side of the reflex pathway. Composite group Ia EPSPs in Holmes-Aide patients with hyporeflexia were smaller than normal or absent, indicating that the areflexia in the Holmes-Aide syndrome is due to loss of large spindle afferents or reduced effectiveness of their monosynaptic connections to motoneurons.     

Loss of facial sweating and flushing in Holmes-Adie syndrome

We investigated pupillary responses to parasympathetic (pilocarpine) and sympathetic agents (tyramine, cocaine, and phenylephrine) in a 51-year-old woman with tonic pupils, loss of muscle stretch reflexes in the limbs, and hemifacial loss of sweating and flushing (Ross' syndrome). A smaller pupillary response to tyramine and cocaine eyedrops on the symptomatic side indicated that outflow was disrupted in the postganglionic section of the ocular sympathetic pathway. A greater response to phenylephrine eyedrops on this side was consistent with denervation supersensitivity to adrenergic agents. Loss of thermoregulatory sweating and flushing and emotional blushing in the forehead, cheek, and chin indicated that sympathetic disruption was proximal to the bifurcation of the common carotid artery, probably in the superior cervical ganglion. A similar degenerative process may be responsible for loss of muscle stretch reflexes, tonic pupils, and other autonomic disturbances in Ross' syndrome.