Autonomic cardiovascular responses in distal myopathy (Welander)

Autonomically mediated cardiovascular responses were evaluated in 9 patients with Welander distal myopathy and compared to data from an age- and sex-matched control group. The myopathy patients had a normal respiratory sinus arrhythmia and a normal heart rate response to the Valsalva menoeuvre, indicating a normal vagal function. They had a normal initial heart rate response to the orthostatic position, indicating a normal function of the sympathetic nerves. The main difference between the groups was found in the orthostatic position. The myopathy patients reacted with a greater increase in systolic blood pressure and a smaller heart rate increase than the controls. This suggests an altered peripheral vasomotor function, possibly with a more predominant activation of alfa than beta adrenergic receptors leading to vasoconstriction. In addition, a low forearm blood flow at rest and a les pronounced blood flow increase during the isometric handgrip were found in the myopathy patients. This finding could also be explained by proneness to vasoconstriction. It is concluded that patients with Welander distal myopathy have no signs of dysfunction of the peripheral autonomic nerves.     

Motor evoked responses from the thigh muscles to the stimulation of the upper limb nerves in patients with late poliomyelitis.

OBJECTIVES: To demonstrate a clear-cut M response recorded from the severely affected thigh muscles to the stimulation of the upper limb nerves in a serial of patients with late poliomyelitis. METHODS: Fifteen patients with late poliomyelitis, 7 patients with spinal cord disorders and 11 control subjects were included. Evoked muscle responses were investigated in quadriceps femoris and/or thigh adductor muscles to the stimulation of the brachial plexus, median and ulnar nerves. RESULTS: Evoked muscle responses were obtained from the thigh muscles in all 12 late polio patients with proximal lower extremity involvement. The response could not be recorded from the thigh muscles neither in the 3 polio patients with upper extremity involvement nor in the healthy control subjects and in patients with other spinal cord disorders of anterior horn cell. CONCLUSIONS: It is proposed that the electrical stimulation of the arm nerves produce interlimb descending muscle responses in the severely affected atrophic thigh muscles of the patients with late polio. This finding suggests that there might be a focal and/or specific loss of inhibitory interneurons between injured and normal motor neurons and increased facilitatory synaptic action at the end of long propriospinal descending fibers in the case of late poliomyelitis.     

Autonomic cardiovascular responses in parkinsonism: effect of levodopa with dopa-decarboxylase inhibition

ABSTRACT – Autonomically mediated cardiovascular responses to certain manoeuvres were studied in 20 parkinson patients, 24 h off levodopa-decarboxylase inhibitor medication and again one h after medication. Results were compared with 15 healthy control subjects. The heart rate at rest was higher in parkinson, the respiratory sinus arrhythmia was lower, while the Valsalva ratio, the heart rate and blood pressure responses during an orthostatic test and the heart rate response to a dive reflex test were normal. These findings indicate a normal function of peripheral autonomic nerves and a possible central parasympathetic dysfunction.
There were significantly attenuated responses of heart rate, blood pressure and contralateral forearm blood flow to an isometric handgrip. Since the peripheral autonomic nerves seemed to be normal, these results could be related to a reduced central command and/or diminished stimulation of postulated peripheral ergoreceptors in parkinsonism.
There was no major effect on the cardiovascular responses by the acutely administered medication.     

Evidence for cardiovascular autonomic nerve dysfunction in multiple sclerosis.

In 21 patients with multiple sclerosis and 20 healthy controls, the following tests of autonomic function were examined: (1) variation in heart rate during deep breathing, (2) the variations in heart rate and systolic blood pressure during a standardised Valsalva manoeuvre, (3) the changes in heart rate and systolic blood pressure during arm ergometry starting at 30 W with increments of 20 W every 3 min. In the control subjects the maximum variation in heart rate from inspiration to expiration was greater than 16 beat/min (range 17-43). In patients with multiple sclerosis, five had a maximum variation in heart rate of less than 13 beat/min which was considered as the lower limit of normal. The Valsalva ratio in the control subjects ranged from 1.33-3.24. Four patients had Valsalva ratios of less than 1.30. In patients with multiple sclerosis the heart rate and systolic blood pressure responses to exercise were attenuated significantly in four and seven subjects respectively. It is concluded that a significant number of patients with multiple sclerosis show evidence of autonomic dysfunction involving the cardiovascular system.     

Neurogenic forearm vasodilatation during contralateral isometric exercise is attenuated in diabetes mellitus

The responses in heart rate, blood pressure and blood flow in the resting forearm during contralateral isometric handgrip were investigated together with the respiratory sinus arrhythmia (measured during standardized breathing frequency and depth), and the heart rate response to a Valsalva manoeuvre in 20 patients with insulin-dependent diabetes and clinical signs of a peripheral neuropathy. The respiratory sinus arrhythmia and the Valsalva ratio were attenuated in the patients compared to age-matched controls, indicating reduced vagal function. Also the responses to handgrip were reduced. The blood flow increase in the resting forearm upon handgrip was correlated with both the respiratory sinus arrhythmia and the Valsalva ratio, supporting neurogenic mediation of the flow response and indicating a reduction in sympathetic as well as vagal function in diabetes autonomic neuropathy.     

Muscle sympathetic activity in cerebellar degeneration with or without mild autonomic dysfunction

To evaluate autonomic function in sporadic cases of cerebellar degeneration (CD) with or without mild autonomic dysfunction, we measured muscle sympathetic nerve activity (MSNA) by microneurography in 12 CD patients and 18 healthy subjects. The burst incidence and mean amplitude of MSNA at rest was significantly decreased in CD patients (P < 0.01). There were no significant differences between patients with CD and controls in heart rate or blood pressure at rest. During head-up tilting, increases in blood pressure and mean amplitude of MSNA were significantly lower in CD patients. In conclusion, a decrease in muscle sympathetic outflow can be observed even in CD patients who are clinically excluded from multiple system atrophy (MSA). It might be difficult to distinguish other CD syndromes from MSA in recordings of muscle sympathetic activity.     

Effect of dermorphin and morphine on the sympathetic and cardiovascular system of the pithed rat

Dermorphin is a recently discovered opioid peptide which is unique in having a D-amino acid in its sequence. Dermorphin binding sites have been shown in central and peripheral organs and central administered dermorphin produces profound autonomic responses. The purpose of this study was to examine the effect of intravenous dermorphin on heart rate and blood pressure of the pithed rat in basal condition and in response to controlled sympathetic stimulation. Also, since dermorphin is a selective mu-receptor agonist, its effects were compared to morphine, an opiate selective for mu receptors. Dermorphin (0.0001-10 mumol/kg, i.v) or morphine (1-10 mg/kg) had no effect on basal heart rate or blood pressure and failed to modify sympatho-adreno-medullary evoked pressor and tachycardic responses. Furthermore, dermorphin or morphine did not affect the increase in plasma norepinephrine and epinephrine in response to spinal cord stimulation. It is concluded that the dermorphin and morphine have no direct peripheral effects on heart rate or blood vessel tone nor do these mu-receptor agonists have any effect on norepinephrine and epinephrine release from the sympathetic nerves and the adrenal medulla in the rat.     

Autonomic nerve and cardiovascular responses to changing blood oxygen and carbon dioxide levels in the rat

Contribution of autonomic nervous system activity to the heart rate and blood pressure responses during chemoreceptor excitations by systemic hypoxia and hypercapnia and to hyperoxia and hypocapnia was analyzed in the urethane-anesthetized, artificially ventilated rats. Systemic hypoxia induced a co-activation of two antagonistic nerves: an increase in cardiac sympathetic and in cardiac vagal efferent nerve discharges. Increased heart rate was due to predominance of the cardiac sympathetic over the cardiac vagal activation. In spite of a marked reflex increase in the renal and cardiac sympathetic nerve activities, the local vasodilator effect of hypoxia prevented consistent changes in arterial blood pressure. Bilateral section of the carotid sinus nerves (CSN) mostly abolished autonomic nerve responses and produced a profound decreases in the blood pressure during hypoxia. Hyperoxia elicited a pressor response due to peripheral vasoconstriction with no significant change in the autonomic nerve activities except for a decrease in the cardiac sympathetic nerve discharges. Hypercapnia significantly increased blood pressure and renal nerve sympathetic activity. In contrast to hypoxia, hypercapnia excited cardiac sympathetic and inhibited cardiac vagal activity. This reciprocal effect did not elicit neurogenic cardioacceleration, because it was masked by the local inhibitory action of CO2 on the heart rate. The increase in sympathetic activities and in blood pressure during hypercapnia persisted after bilateral CSN section indicating that the responses were mediated by central rather than by peripheral chemoreceptors. Hypocapnia produced a significant increase in cardiac vagal discharges yet a cardioacceleratory response occurred due to the local effect upon heart rate. The present results indicate that in the rat, autonomic nervous responses differ depending on the type, i.e. hypoxic or hypercapnic, chemoreceptor stimuli. Reflex heart rate and blood pressure responses do not follow the autonomic nerve activities exactly. Circulatory responses are greatly modified by local peripheral effects of hypoxic, hyperoxic, hypocapnic or CO2 stimuli on the cardiovascular system. Species differences characterizing the autonomic nerve responsiveness to chemical stimuli in the rat are described.     

Autonomic function in amyotrophic lateral sclerosis: a study of cardiovascular responses

Autonomically mediated cardiovascular responses were evaluated in 15 ALS patients and compared with 15 healthy subjects. The respiratory sinus arrhythmia, the heart rate response to a Valsalva manoeuvre, to isometric handgrip and to a dive reflex test was normal, indicating a normal function of vagal nerves. The heart rate and blood pressure responses during an orthostatic test were normal, indicating a normal function of sympathetic nerves. The increase in blood pressure and blood flow in the contralateral forearm which occurs on handgrip in healthy subjects was reduced in the ALS patients. The cause of this is unclear, but could be related to decreased function of "ergoreceptors" or altered vascular reactivity in atrophic muscle.     

Autonomic dysfunction and hemodynamics in vitamin B12 deficiency

Orthostatic hypotension in patients with cobalamin (Cbl) deficiency has been reported previously in isolated cases but we are not aware of detailed systematic studies of hemodynamic and autonomic nervous system function in patients with cobalamin deficiency. We investigated hemodynamic and autonomic responses to 60 degrees passive head up tilt (HUT) in 21 patients with vitamin B12 deficiency, 21 healthy age-matched control subjects and 9 age-matched patients with diabetes mellitus (DM) and established diabetic neuropathy. To systematically assess hemodynamic and autonomic nervous system function, we performed measurements of heart rate, beat-to-beat systolic and diastolic blood pressure, stroke index, cardiac index, total peripheral resistance index, total power, low (LF) and high (HF) frequency oscillatory component of heart rate variability, LF/HF ratio and spontaneous baroreflex sensitivity. As compared to controls, we found a significant fall of systolic blood pressure during 60 consecutive beats directly after head up tilt; furthermore, a significantly blunted fall of stroke index, cardiac index and a lack of increase of total peripheral resistance index for the duration of tilt in patients with diabetes mellitus and in patients with vitamin B12 deficiency. As compared to controls, we observed an altered response of spectral indices of sympathetic activation and vagal withdrawal and an impaired modulation of baroreflex sensitivity during head up tilt suggestive of a complex modification in the neural control activities in patients with cobalamin deficiency, which was comparable to that observed in patients with diabetes mellitus and established autonomic neuropathy. The results suggest that vitamin B12 deficiency causes autonomic dysfunction with similar hemodynamic consequences and patterns of autonomic failure as seen in diabetic autonomic neuropathy. Defective sympathetic activation may be the cause for orthostatic hypotension, which is occasionally seen in patients with vitamin B12 deficiency. It is concluded that patients with orthostatic hypotension should be screened for cobalamin deficiency.     

Autonomic consequences of brainstem infarction

OBJECTIVE: It is well known that patients with brainstem infarctions sometimes experience dizziness, vertigo and falls, although the exact mechanism is not clear. Therefore, we designed a study to quantify autonomic function in patients with brainstem infarction. PATIENTS AND METHODS: We examined autonomic function in 15 patients with brainstem infarctions, who had a history of vertigo, nausea, floating sensation and/or general fatigue during standing, and 31 age-matched controls using the composite autonomic scoring scale (CASS), which was used to grade autonomic function. The patients underwent initial autonomic assessment and then were subjected to aniracetam therapy. The drug was given orally (dose of 600 mg/day) for a duration of 56 days. Upon completion of aniracetam administration, the CASS was again tested. RESULTS: Upon initial assessment, the patients had mild reductions in mean blood pressure (MBP) and lack of an increasing heart rate (HR) within 5 min of head up-tilt, an impairment in BP correction during late phase II and reduced phase IV beat-to-beat BP response to the Valsalva maneuver, and reduced heart rate response to deep breathing (HRdb). CASS indicated mild autonomic dysfunction. After 8 weeks of treatment with aniracetam, the patients' symptoms improved and the autonomic tests showed improvement in autonomic function. CONCLUSION: Part of the pathogenesis of recurrent vertigo or dizziness with brainstem infarction might be due to mild autonomic dysfunction. Aniracetam, which activates the cholinergic system in brain, might correct the cardiovagal system in these patients. The CASS may be a sensitive tool for assessing mild autonomic dysfunction in patients with brainstem infarction.     

Amyotrophic lateral sclerosis in an adult following acute paralytic poliomyelitis in early childhood

About 30% of polio survivors develop a post-polio syndrome. Some of these patients develop slowly progressive muscle weakness known as post-poliomyelitis muscular atrophy (PPMA). We describe an unusual form of amyotrophic lateral sclerosis (ALS) in a patient with acute poliomyelitis in childhood. An 80-year-old woman had acute poliomyelitis at 2 years of age and developed weakness limited to the lower extremities. Residual weakness was stable until the age of 75 when she developed rapidly progressive weakness that first affected her left arm and subsequently the right arm. Neurological examination revealed both upper and lower motor neuron signs. These clinical features were more consistent with ALS than PPMA. At autopsy, there was marked atrophy of the precentral gyrus. Microscopic examination revealed a severe loss of all nerve cells and pronounced fibrillary astrocytosis of the lumbar ventral horns in the spinal cord, presumably a result of poliomyelitis. Superimposed on these spinal cord alterations were the pathological features of ALS, consisting of loss of Betz cells, corticospinal tract degeneration and loss of motor neurons of other levels of the spinal cord. The findings included some atypical features for ALS, namely, sparing of the hypoglossal nucleus, absence of Bunina bodies and absence of ubiquitin-immunoreactive inclusions. Although poliomyelitis and ALS may be coincidental, the unusual pathological expression of ALS raise the possibility that it is related to the antecedent poliomyelitis. Received: 19 November 1997 / Revised: 24 April 1998, 6 September 1998 / Accepted: 14 September 1998     

Basal sympathoadrenal function in posttraumatic distress disorder.

Research has consistently shown that patients with posttraumatic stress disorder (PTSD) manifest greater changes in heart rate, blood pressure, and plasma epinephrine than controls when exposed to trauma-related laboratory stressors. However, findings are equivocal as to whether PTSD subjects differ from controls on basal, or tonic, measures of autonomic activity. In this study, PTSD patients (n = 11) and asymptomatic controls (n = 11) were compared on measures of basal sympathoadrenal function, including plasma norepinephrine and epinephrine as well as heart rate and blood pressure. Results showed that PTSD patients were not significantly different from control subjects on any measure. Although phasic alterations in autonomic function in PTSD have been consistently found in previous research, this study suggests that tonic sympathetic nervous system activity in PTSD patients may not differ from that of healthy controls.     

Nutritional status and autonomic nervous system function

Autonomic function was studied in 20 undernourished subjects without medical or neurologic disease (aged 20 to 66 years, mean age 36) and compared to 30 well nourished subjects (age 20 to 65 years, mean age 40). Anthropometric measurements were performed (height, weight, triceps skinfold thickness, arm muscle circumference). The Valsalva manoeuvre and the immediate heart rate response to lying down test (S/L) were performed to study autonomic functions. The Valsalva ratio was 1.56 +/- 0.29 for controls and 1.66 +/- 0.34 for undernourished subjects (p greater than 0.1). The S/L ratio showed a significant difference (p less than 0.001) between controls (1.278 +/- 0.13) and undernourished subjects (1.06 +/- 0.07).     

Electrophysiological tests of autonomic function in patients with idiopathic autonomic failure syndromes

Three electrophysiological tests of autonomic function were performed in patients with autonomic nervous system dysfunction to define test sensitivities and specificities. The skin sympathetic response, Valsalva ratio, and heart rate variation with deep breathing were studied in 10 patients with multiple system atrophy (MSA) and in 7 patients with pure (also called progressive or primary) autonomic failure (PAF); control subjects were 17 normal individuals of similar age. Thirteen patients had abnormal skin sympathetic responses, and 16 had abnormal Valsalva ratios. Fourteen patients had an abnormal variation of the heart rate with deep breathing. Taking the three tests together, binary logistic regression for distinguishing between patients and normal subjects correctly classified 91% of the 33 individuals for whom there were complete data with sensitivity of 88% and specificity of 94%. However, only 69% of the patients could be correctly classified by a logistic regression for discriminating between MSA and PAF. Electromyography (EMG) studies showed that 7 of 8 patients with MSA but only 2 of 7 patients with PAF (both multiparous women) had denervation of the rectal sphincter muscle. The EMG study is, therefore, valuable in men, but has a high false positive rate in women, probably because of pudendal nerve injury from parturition. © 1996 John Wiley & Sons, Inc.     

Differences in cardiovascular responses to supine exercise and to standing after exercise in two clinical subgroups of Shy-Drager syndrome (multiple system atrophy).

BACKGROUND: In chronic autonomic failure of varying aetiologies, there are differences in the cardiovascular responses to supine leg exercise and to standing after exercise. Whether this occurs between the different subgroups with Shy-Drager syndrome (SDS) is unknown. METHODS: Fourteen patients with the cerebellar form (SDS-C) and 11 patients with parkinsonian features (SDS-P) were studied. RESULTS: Both groups had a similar degree of autonomic failure and postural hypotension. Their responses were compared with nine patients with idiopathic Parkinson's disease (IPD) and 15 normal subjects (controls), all with normal autonomic function. With supine exercise, blood pressure and heart rate rose similarly in controls and patients with IPD and there was no fall in blood pressure on standing after exercise. In both SDS groups there were abnormal responses to exercise: blood pressure fell in SDS-C, but did not fall or rise in SDS-P. Heart rate increased similarly in both SDS groups, calculated systemic vascular resistance fell similarly, but cardiac index rose more in SDS-P than SDS-C. Resting plasma noradrenaline concentrations were subnormal in both forms of SDS, and did not increase with exercise. Postural hypotension was enhanced after exercise to the same extent in SDS-C and SDS-P. CONCLUSIONS: The greater cardiovascular abnormalities in response to exercise in SDS-C suggests that cerebellar or brain stem autonomic pathways are impaired to a greater extent in SDS-C than in SDS-P. Pooling SDS subgroups, therefore, may obscure pathophysiological differences to certain stimuli. Clinically when postural hypotension is being assessed, separation of the subgroups may not be essential, as they responded similarly.     

Prior poliomyelitis-reduced capillary supply and metabolic enzyme content in hypertrophic slow-twitch (type I) muscle fibres.

Capillary supply and oxidative and glycolytic enzyme activities were determined in muscle biopsies from the tibialis anterior muscle in six prior polio patients and a control group. The polio patients, who had paresis and atrophy, but were able to walk normally by making maximal use of all remaining anterior tibial motor units, showed type I (slow-twitch) muscle fibre predominance with a mean (SD) of 98 (2%) type I fibres versus 81 (8)% in the controls (p less than 0.01) and muscle fibre hypertrophy, the average type I fibre cross-sectional area being 108% (p less than 0.005) larger than in the controls. The number of capillaries per muscle fibre was not significantly different from that in the control group, but with the increased muscle fibre area in the polio patients, the capillary density was significantly lower. The number of capillaries in contact with type I fibres relative to fibre area was 40% lower in the patients than in the controls (p less than 0.005). The levels of citrate synthase and phosphofructokinase were significantly lower (38% and 33%, respectively, p less than 0.05) in the patients than in the controls, indicating decreased oxidative and glycolytic potentials in the muscle fibres of the polio patients. It is proposed that the abnormal high-frequency activation of all remaining motor units during each step cycle recorded in these patients constitutes a stimulus for type I muscle fibre predominance and hypertrophy but that the overall low muscle usage results in a decreased stimulation of capillary proliferation and mitochondrial enzyme synthesis. The low capillary density and decreased oxidative and glycolytic enzyme potentials might be important factors for the development of muscle weakness, fatigue and muscle pain, which are commonly occurring symptoms in patients with prior poliomyelitis.     

Postprandial and orthostatic hypotension in Parkinson's disease

In this study, the 24-hour pattern of blood pressure (BP), heart rate, and urinary catecholamine (CA) excretion and the response of BP and plasma CA to the tilt test have been investigated in 13 untreated patients affected by Parkinson's disease (PD) and in 11 age-matched healthy controls. Seven of the 13 PD subjects showed a fall of supine systolic BP greater than that in controls (ie, exceeding 20% of the preprandial value). A significant relationship was found in the PD group between the degree of postprandial hypotension and the 24-hour mean value of dopamine excretion. Eight PD subjects also showed orthostatic hypotension during the tilt test (performed in the morning hours) and in the postprandial phase. Basal norepinephrine plasma levels of PD patients, as well as their percentage increases on standing, were within the range of the controls. These data suggest the existence of a subtype of PD patient, characterized by a widespread impairment of cardiovascular responsiveness and bordering on syndromes of autonomic failure such as progressive autonomic failure or multiple system atrophy, or both.     

Impaired cardiovascular autonomic control in newly and long-term-treated patients with Parkinson's disease: involvement of L-dopa therapy

In idiopathic Parkinson's disease (PD), autonomic dysfunction is frequent, causing orthostatic hypotension. The respective roles of disease progression and dopaminergic treatment remain unclear. In this study, we investigated the autonomic control of cardiovascular functions and its relation to L-dopa therapy in both newly diagnosed (ND) and long-term-treated (LT) patients. Study subjects were: (1) nine ND patients never having undergone treatment with L-dopa; (2) 18 LT patients who had been receiving L-dopa treatment for a long period. ND patients were investigated before L-dopa treatment and after stabilization of their L-dopa dosage. LT patients were investigated once with their regular treatment and once after a 12-h interruption of L-dopa treatment; (3) nine healthy subjects served as controls. At each test session, blood pressure (BP), heart rate (HR), plasma catecholamines, heart rate variability (HRV), and spontaneous baroreflex sensitivity were assessed in the supine and upright positions. Before receiving L-dopa medication, ND patients had reduced E/I ratios (HR response/deep breathing) and lowered HRV when compared to controls; this was evidence of early effects of the disease on autonomic HR control. Introduction of L-dopa treatment reduced BP, HR, and plasma levels of adrenaline and noradrenaline. Similar changes were found in LT patients when contrasting the short-term treatment interruption and the usual L-dopa dosage. The treatment-linked increase in plasma dopamine also correlated with the decrease in noradrenaline. These results showed that mild impairment of autonomic cardiovascular control occurred early in the course of PD. They also provided evidence that the side effects of L-dopa aggravated the impairment of the autonomic control of BP and HR.     

Post-poliomyelitis late progressive muscular atrophy (PPMA)--clinical analyses of Japanese cases]

Clinical and epidemiologic analyses of PPMA in Japan based on the nation-wide case survey were reported, and differences between PPMA and ALS were discussed. The present survey covering the years from 1984 through 1991 cited 42 PPMA cases (30 male:12 female). The absolute incidence of PPMA is estimated 0.12/10(5) of the Japanese population (about 150 cases in total), which indicates 0.5% of the polio survivors. In Japan an actual increase of patients is noticed in these 10 years, which reflects the big epidemic of polio around 1950-60. The antecedent poliomyelitis occurred at the mean age of 2.6, mostly between 1940 and 1960. Residual paralysis was generally absent or only minimal. Late muscular atrophy and weakness were noticed at age from 16 to 63 y (mean:41.5), with the mean latency of 40.1 years after polio. Both polio-affected and unaffected site of the limb were equally involved by PPMA, but the left leg tends to be predominantly involved. Neurological symptoms were summarized as an asymmetrical proximal muscular atrophy and flaccid motor paresis in one or two limbs with decreased tendon reflexes. Fasciculation in 45.2%, myalgia in 28.6%, and hypesthesia in 28.5% were noticed. Electromyography and muscle CT scan showed marked selective neurogenic changes. In most cases symptoms are stable or slowly progressive, with some recovery by rest or rehabilitation and deterioration by over work and/or trauma. On regarding these clinical features, PPMA is essentially different from classical ALS. Long-term hyperfunction of survived neurons with potential fragility by polio infection is suspected to mediate PPMA.(ABSTRACT TRUNCATED AT 250 WORDS)