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PubMed2002

[High level of stress and immature defense make for a vicious circle in chronic pain. Patients with pain syndromes caught in unresolved crisis as a study shows].

Extended pain includes human beings of all categories and can lead to a life crisis, a high stress level and dysfunctional psychological defences that can be accompanied by difficulties within new orientation. The diagnosis of pain disorder is often undetected among patients with unspecific symptoms. This increases the risk of inadequate treatment that can contribute to maintaining a lengthy state of pain. Professional care of the patient is built on a common conception by both health and hospital staff, based on the respect for the patient's lifestyle and environment. Studies have integrated qualitative and quantitative methods in analogy with interdisciplinary sciences. Quantitative methods in the form of structured estimating instruments can show regularities in multiple dimensional patterns, whereas qualitative methods show processes based on the variables that are identified. The aim is to deepen the knowledge of thirty patients with pain syndrome in comparison with a reference group, consisting of thirty patients with recognised organic causes of pain. The results of the study conclude that patients with pain disorder have in comparison to patients with objective organically related pain, the following: An increased usage of undeveloped defences, a reduced repertoire of mastering strategies, a continuing reaction to crisis, an increased autonomic dysfunction, a greater risk of deterioration and being excluded from the workplace, a description (by the patient) of difficult traumatic events in his/her background history.

Adult↗

PubMedDate not supplied

Effects of arginine-vasopressin on regional blood volume distribution in supine humans.

In healthy humans, the increase in arterial blood pressure seen in patients with autonomic dysfunction in response to exogenous vasopressin (AVP) is abolished. We tested the hypothesis that redistribution of blood from the intra- to the extrathoracic vascular compartment might contribute to this buffer response. Regional distribution of 99mTc labeled autologous red cells was assessed in healthy supine volunteers (n = 7) during arginine-vasopressin administration (1 ng.kg-1 bolus i.v. followed by a 14-min infusion of 3 ng.kg-1 x min-1), along with arterial and central venous pressures, and heart rate. Exogenous vasopressin increased plasma vasopressin concentration from 4.0 +/- 1.4 SEM to 91 pg.ml-1 +/- 12. Thoracic counts increased slightly but significantly by 2.2% +/- 0.9, while global abdominal counts remained unchanged. Most surprisingly, counts in the liver markedly increased (+8.1% +/- 1.8, p = 0.02), but significantly decreased in the spleen (-3.1% +/- 1.4). Intestinal (-2.5% +/- 2.4) and limb counts did not change significantly. Consistent with the increase in thoracic counts central venous pressure increased from 3.6 mmHg +/- 1 to 4.7 +/- 1 (p = 0.02), while arterial pressure and heart rate did not change. All changes reversed towards baseline when vasopressin administration ceased. Thus, in humans with an intact autonomic system, vasopressin, at concentrations observed during hypotension, increases liver and, albeit to a small extent, also thoracic blood volume, but decreases splenic blood content. These results: 1) are incompatible with the hypothesis that AVP induces a shift of blood from intra- to extrathoracic capacitance vessels, and 2) show that AVP increases rather than decreases central blood volume.

Adult↗

PubMed1982

The effect of captopril on postural hemodynamics and autonomic responses in chronic heart failure.

Both postural abnormalities and autonomic dysfunction have been identified in patients with chronic congestive heart failure (CHF). However, the effect of long-term vasodilator therapy on these phenomena has not been assessed. In this study the hemodynamic and plasma norepinephrine (PNE) responses to upright posture, as well as the cold pressor test and Valsalva's maneuver in 12 patients with severe chronic CHF during both acute and long-term captopril (CPT) therapy, were evaluated. This revealed an absence of the normal hemodynamic adjustments to upright posture and a blunted response of PNE. The heart rate and blood pressure responses to the cold pressor test and Valsalva's maneuver were similarly blunted. The reflex adjustments of systemic resistance during tilt improved with CPT therapy, but the absence of reflex tachycardia in the upright posture persisted. Additionally, there was improvement of the PNE response, and the responses of heart rate and blood pressure to the cold pressor test were virtually normalized during long-term CPT therapy. The abnormal response to the Valsalva maneuver persisted. In conclusion, hemodynamic and reflex-mediated responses to upright posture and the standard assessment of autonomic control mechanisms revealed abnormal patterns in heart failure. While the hemodynamic adjustment to postural changes and sympathetic responsiveness were improved with CPT, complete correction of these abnormalities did not occur. Whether the improvement was a nonspecific vasodilator effect or the result of specific CPT therapy remains to be determined.

Adult↗

PubMed1994

Scopolamine improves autonomic balance in advanced congestive heart failure.

BACKGROUND: Sympathetic hyperactivity and parasympathetic withdrawal in patients with congestive heart failure correlate closely with disease severity and overall survival. The modulating effects of drugs on the autonomic dysfunction may contribute to improve survival. Low-dose scopolamine has a vagomimetic effect in normal subjects and patients after acute myocardial infarction. We assessed whether transdermal scopolamine would increase vagal activity in patients with congestive heart failure. METHODS AND RESULTS: Heart rate variability was assessed at baseline, 24 hours after one patch of transdermal scopolamine, and 48 hours after scopolamine withdrawal in 21 patients with moderate to severe heart failure. Scopolamine increased both time- and frequency-domain parameters of heart rate variability. Specifically, the mean RR interval and its SD increased by 5.5% (P < .001) and 45% (P < .001), respectively. The change remained significant when corrected for mean heart rate with a 39% (P < .01) increase of the coefficient of variation. The absolute power of the high-frequency component was also significantly augmented. All the parameters returned to baseline after scopolamine withdrawal. Individual analysis showed that in the 7 patients in whom scopolamine did not increase mean RR interval, heart rate variability did not change. CONCLUSIONS: Transdermal scopolamine increases vagal activity as assessed by heart rate variability in patients with congestive heart failure. This autonomic modulation does not occur in all patients and can be predicted by RR interval changes. Whether such restoration of the autonomic balance might have beneficial effects in the long-term management of patients with congestive heart failure remains to be determined.

Administration, Cutaneous↗

PubMed1995

Some specific clinical features differentiate multiple system atrophy (striatonigral variety) from Parkinson's disease.

OBJECTIVE: The clinical recognition of multiple system atrophy (MSA) in patients presenting with parkinsonian signs is difficult. We attempted to verify the predictive value of some pointers that are used in clinical practice. DESIGN: Sixteen consecutive patients with pathologically confirmed MSA who presented with a parkinsonian syndrome over an 8-year period were studied retrospectively, and their clinical features were analyzed in detail. SETTING: Parkinson's Disease Society, Brain Tissue Bank, Institute of Neurology, London, England. PATIENTS: Sixteen patients with pathologically proven MSA who presented with parkinsonian syndrome in the first 3 years since disease onset. METHODS: Clinical features that were analyzed included the rapidity of disease progression, the relative symmetry of symptom onset, the presence or absence of tremor at initial presentation, the therapeutic response to levodopa and the associated presence of autonomic dysfunction. Fourteen of the 16 patients also had a computed tomographic scan of the brain performed. The frequency of selected items in MSA was compared with that found in 20 pathologically confirmed cases of Parkinson's disease and 16 pathologically confirmed cases of progressive supranuclear palsy (Steele-Richardson-Olszewski disease). RESULTS: It was found that a probability scale based on five selected items discriminated MSA with a pure parkinsonian presentation from Parkinson's disease, but not from progressive supranuclear palsy. Patients affected by the latter disorder, however, commonly presented with additional clinical features (supranuclear vertical down-gaze palsy, axial dystonia, and cognitive impairment), which helped to differentiate it from MSA.

Autonomic Nervous System Diseases↗

PubMed1992

Familial amyloid polyneuropathy related to transthyretin Gly42 in a Japanese family.

A Japanese family is described in which 6 persons showed familial amyloid polyneuropathy (FAP). Mean ages of onset were 38 for 4 males and 54 for 2 females. Three of the 6 became emaciated and died after 4 to 10 years. In 5, muscular weakness and autonomic dysfunction were the initial symptoms followed by sensory disturbances. Amyloidotic cardiomyopathy was present in 3 of the subjects. Amyloid deposits showed an immunohistological relation to transthyretin (TTR). Analysis of 1 patient's TTR gene revealed a single base change (A----G) that led to amino acid substitution (Glu42----Gly). This base change produced a new restriction site for endonuclease Cfr13 I in exon 2. Polymorphic analysis of the length of the Cfr13 I-restriction fragment confirmed the base change, and made it possible to detect the mutant TTR Gly42 gene in the FAP subjects. Amino acid sequencing analysis showed a variant of TTR Gly42 in 1 patient's serum.

Adult↗

PubMed2000

Brainstem-type Lewy body disease presenting with progressive autonomic failure and lethargy.

The authors report an autopsy case characterized by progressive lethargy and autonomic failure with a distinctive pattern of occurrence of Lewy bodies. Autonomic dysfunction such as sleep apnea, orthostatic hypotension, dysuria, and hypohidrosis predominated with lethargy, whereas parkinsonism was not apparent. Numerous Lewy bodies were widely evident microscopically in brainstem nuclei and the intermediolateral cell columns of the spinal cord, as well as in the sympathetic ganglia, but were rare or absent in the cerebral cortex and other supratentorial structures. Marked neuronal loss was seen in the locus ceruleus, raphe nuclei, dorsal vagal nuclei, and intermediolateral cell columns, but neurons in the substantia nigra, other brain regions, and sympathetic ganglia appeared undiminished. This case represents a specific clinicopathologic form of Lewy body disease occurring predominantly in the brainstem, spinal cord, and sympathetic ganglia.

Autonomic Nervous System↗

PubMed2005

Analysis of heart rate variability in female patients with overactive bladder.

OBJECTIVES: To characterize autonomic dysfunctions in patients with an overactive bladder (OAB), we compared their heart rate variability (HRV) with the HRV of a normal population. METHODS: Electrocardiographic signals were obtained from 40 female patients (mean age 46.4 +/- 12.1 years) and 131 healthy female controls (mean age 45.6 +/- 7.24 years) in a resting state. RESULTS: The time domain analysis of the electrocardiographic signals for patients with OAB, including the standard deviation of the N-N interval and the square root of the mean squared differences of successive N-N intervals, revealed significantly lower values than those of the controls (P <0.05). Evidence was found of decreased total power, very low frequency, and high frequency signals in patients with OAB (P <0.05), but no significant differences were found in other parameters such as low frequency or the low frequency/high frequency ratio. CONCLUSIONS: Patients with OAB exhibited different HRV parameters compared with normal controls. With the exception of low frequency and the low frequency/high frequency ratio, all HRV parameters in patients with OAB were lower than those in normal controls. These decreased values indicate that they may have some kind of disease or imbalance in the autonomic nervous system. Thus, a study of HRV may serve as a tool to evaluate altered autonomic nervous system activity in such patients.

Electrocardiography↗

PubMed2002

[Autonomic nervous system function and effects of beta-adrenoblockers on heart rhythm variability in patients with myocardial infarction].

Heart rhythm variability on myocardial infarction (MI) day 1, 3, 7 and 11 was assessed mathematically to study function of the autonomic nervous system in 101 MI patients. The initial autonomic tonicity (IAT), autonomic reactivity (AR) and autonomic maintenance (AM) were studied. Depending on the site of the infarction in the myocardium, different type of autonomic homeostasis were identified. Moderate sympathicotonia, sympathicotonic type of AR and adequate AM irrespective of IM location were found most favourable in relation to the MI course and prognosis. The spectral analysis of the heart rhythm showed a significant shift of the frequency spectrum in the inferior MI to high frequencies and in anterior MI--to low frequencies. Autonomic dysfunction score is higher in the anterior MI. Psychoemotional state of the patients was determined by Spilberg-Khanin test evaluating reactive and personality anxieties. These characteristics were moderate and high in patients with MI and effort angina, respectively. The study of selective beta-adrenoblockers effect on heart rhythm variability proved that lokren (betaxolol) in a dose of 10 mg/day significantly and positively influences heart rhythm and objective status of the patients. Less effective is betacard (atenolol). Nebivolol is not indicated in acute MI. Significant correlations are found between the findings of IAT mathematical analysis, psychoemotional features of the patients and complications of MI. Parameters of an unfavourable course and outcome of MI are described.

Adrenergic beta-Antagonists↗

PubMed1995

Ambulatory blood pressure monitoring and cardiovascular function tests in multiple system atrophy.

Cardiovascular tests (CT) of autonomic function and non-invasive ambulatory blood pressure (BP) and heart rate (HR) monitoring were performed in 17 patients with multiple system atrophy (MSA) (mean age 61 +/- 9 years) and in 12 healthy subjects matched for sex and age. CT showed severe autonomic dysfunction with orthostatic hypertension (OH) in eight patients with MSA (47%) (Group I). The remaining nine out of the 17 patients didn't show BP abnormalities during CT but an impaired HR reflex response was found (Group II). BP monitoring showed a reversed circadian BP rhythm in Group I with higher night-time than day-time values, a blunted circadian BP pattern in Group II and a normal day-night BP reduction in controls. Day-night HR reduction was poor in Group II and absent in Group I. Post-prandial hypotension was evaluated after a standard meal. In Group I systolic/diastolic BP fell within 30 minutes after meal (from 135 +/- 16/89 +/- 13 to 118 +/- 17/73 +/- 12 mmHg; p < 0.05) and after two hours had not returned to basal levels. In Group II a reduction of only systolic BP was found within 45 minutes after meal and persisted for one hour. OH clinically identifies a subgroup of MSA patients with a more severe BP dysregulation characterized by severe post-prandial hypotension and reversed circadian BP rhythm. CT and ambulatory BP monitoring are useful tools in identifying early stage of cardiovascular autonomic impairment.

Adult↗

PubMed2000

Inhibitory effects of muscarinic receptor autoantibodies on parasympathetic neurotransmission in Sjögren's syndrome.

OBJECTIVE: Sjögren's syndrome (SS) is an autoimmune disorder characterized by dry eyes and mouth (sicca syndrome) and lymphocytic infiltration of the lacrimal and salivary glands. Abnormalities of parasympathetic neurotransmission may contribute to the glandular dysfunction. In this study, we used a functional assay to investigate autoantibody-mediated effects on parasympathetic neurotransmission and smooth muscle contraction. METHODS: Serum and purified IgG were obtained from patients with primary and secondary SS and from control subjects. Contraction of isolated bladder strips in response to stimulation of M3-muscarinic receptors by a muscarinic receptor agonist, carbachol, or by endogenous acetylcholine released from postganglionic parasympathetic nerves was measured before and after the addition of patient serum or IgG. RESULTS: Sera from 5 of 9 patients with primary SS and from 6 of 6 patients with secondary SS inhibited carbachol-evoked bladder contraction by approximately 50%. Sera from these patients also inhibited the action of neuronally released acetylcholine at M3-muscarinic receptors. Sera from 7 of 8 healthy individuals, from patients with rheumatoid arthritis without sicca symptoms, and from patients with systemic lupus erythematosus had no effect. The anti-muscarinic receptor activity was localized in the IgG fraction, since purified IgG from patients with SS also inhibited agonist- and nerve-evoked contractions. In this preliminary study, the autoantibodies seemed to be associated with the presence of bladder symptoms and other autonomic features. CONCLUSION: Autoantibodies that act as antagonists at M3-muscarinic receptors on smooth muscle occur in a subset of patients with primary and secondary SS. Their presence in secondary SS was unexpected and provides new evidence for a common pathogenetic link between primary and secondary SS. These autoantibodies appear to contribute to sicca symptoms and may explain associated features of autonomic dysfunction in some patients.

Acetylcholine↗

PubMedDate not supplied

[Effects of intracranial hypertension on gastric myoelectrical activity evaluated by using clinical and radiological symptoms].

BACKGROUND AND PURPOSE: Acute and chronic increases in intracranial pressure (ICP) cause a dramatic autonomic dysfunction. The aim of the study is to evaluate effects of acute and chronic ICP on gastric myoelectrical activity. MATERIAL AND METHODS: We studied 80 patients hospitalized in the Department of Neurotraumatology of the Jagiellonian University Medical College. The control group included 16 healthy volunteers matched with gender and age. Gastric myoelectrical activity was captured with cutaneous electrodes and Synectics (Sweden) system of storing and analyzing the data. RESULTS: Results of the study were analyzed in the Department of Pathophysiology of the Jagiellonian University Medical College. Most significant changes on gastric myoelectrical activity were observed in patients after a severe head injury with acute intracranial hypertension (Glasgow Coma Scale: 4-7 points). The percentage of bradygastria timing increased up to 50%. In this group of patients the increase in amplitude of the signal was observed. Significant dysrhythmias up to 40% occurred in patients with chronic increase of intracranial pressure caused by brain tumors. CONCLUSIONS: Most significant changes on gastric myoelectrical activity were observed in patients after a severe head injury with acute intracranial hypertension (Glasgow Coma Scale: 4-7 points). The percentage of bradygastria timing increased up to 50%. Gastric dysmotility was caused by stimulation of both arms of the autonomic nervous system.

Acute Disease↗

PubMed2004

Cardiac autonomic balance and QT dispersion during head-up tilt testing in diabetics with and without sensory neuropathy.

BACKGROUND: Cardiovascular autonomic dysfunction is associated with higher mortality in diabetics. However, detection methods of early cardiac diabetic dysautonomia, and its correlation with severity of sensory neuropathy, have not been described. METHODS: We analyzed the heart rate variability (HRV) by spectral analysis and QT dispersion in 23 diabetics with and without sensory neuropathy, and in 5 age-matched controls, in the supine position and during head-up tilt testing (HUT). Diabetics were divided into 3 groups according to the degree of sensory neuropathy. RESULTS: In the spectral analysis of HRV, the high frequency components in the supine position decreased as a function of severity of the neuropathy. High frequency in diabetics was significantly decreased in the supine position, even in absence of sensory neuropathy. The low/high frequency ratio (L/H) in the supine position was similar among controls and the 3 patient groups. L/H in diabetics with moderate or severe neuropathy did not increase from the supine to the upright position. Baseline QT dispersion increased proportionally to the severity of sensory neuropathy and, in patients without apparent sensory neuropathy, QT dispersion increased significantly during HUT. CONCLUSIONS: The spectral analysis of HRV and measurements of QT dispersion, before and during HUT, were reliable detection methods of early abnormalities in autonomic balance and may predict a risk of sudden cardiac death in diabetics.

Aged↗

PubMed1989

[Postganglionic sudomotor function in multiple system atrophy].

Postganglionic sudomotor function were examined on 12 patients with multiple system atrophy (MSA) consisting of 5 males and 7 females with the clinical duration of 1 to 10 years, and with the age ranged 51 and 70 years. Sixteen healthy volunteers, aged 38 to 75 years were also examined as the control. Local sweating induced by intradermal injection of pilocarpine and nicotine (a concentration of 10(-4) g/ml) was quantitatively measured on the volar surface of the forearm and lower lateral leg using a ventilated capsule method in a climatic chamber at 23 degrees C and 40% of relative humidity. Maximal sweat rate induced by nicotine and pilocarpine was significantly reduced in patients with MSA as compared with controls in both the forearm and lower lateral leg. MSA cases associated with more prominent autonomic dysfunction as well as hyposweating, showed a more remarkable impairment of local sweat responses. Particularly, in 6 cases with Shy-Drager syndrome, there was no sweat response by the injection of both pilocarpine and nicotine. The study of an autopsied case with Shy-Drager syndrome revealed neurons in the para-vertebral sympathetic ganglia were well populated, though neurons in the lateral horns of the lower thoracic spinal cord were almost completely depleted. This substantial discrepancy between the impaired sudomotor function and morphological findings may imply several hypothetical views on the mode of pathology of postganglionic sudomotor nerves. The present results, however, strongly suggested that postganglionic sudomotor functions are more extensively involved in patients with MSA than had ever been believed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed2000

Spectral analysis of left ventricular area variability as a tool to improve the understanding of cardiac autonomic control.

Spectral analysis of the fluctuations in heart rate (HR) or blood pressure (BP) has been extensively used as a tool for the noninvasive assessment of autonomic control of the heart. The recently developed echocardiographic acoustic quantification allows noninvasive continuous measurement of the left ventricular cross-sectional area (LVA) signal. In this study, we investigated whether the LVA signal, and more specifically its fluctuations, can be reliably subjected to spectral analysis, and whether the results of such analysis may improve the understanding of the cardiovascular control mechanisms. Our results show that the general pattern of power spectra of LVA fluctuations, as well as their reproducibility, is similar to the power spectra of HR and BP fluctuations. Analysis of LVA signals obtained in normal subjects at rest as well as under vagal blockade and under held respiration, and in patients with known autonomic dysfunction, showed significant differences between groups and states. The effects of age, related to the reduction in parasympathetic activity, were not evident in the spectral content of the LVA and BP signals. The high frequency LVA fluctuations are mainly of mechanical origin, since they were eliminated by breath-holding. We observed an increase in the high frequency LVA fluctuations under vagal blockade, indicating that under normal (control) conditions, these high frequency fluctuations are attenuated by parasympathetic activity. The enhancement in high frequency fluctuations in LVA observed in diabetic patients can thus be attributed to reduced parasympathetic activity. The analysis of LVA variability may be used as a tool for basic research and, possibly, as a quantitative clinical measure for specific disease states.

Adolescent↗

PubMed1992

Repeatability of measurements and sources of variability in tests of cardiovascular autonomic function.

OBJECTIVE: To determine the repeatability and sources of variability of clinical tests of cardiovascular autonomic function. DESIGN: The commonly used electrocardiographic related tests of autonomic function were studied. Two repeat measurements of all tests were made on all subjects on four separate days over a four week period. SUBJECTS: Ten normal subjects with no known autonomic dysfunction were investigated. MAIN OUTCOME MEASURES: These were deep breathing (subject seated and supine), Valsalva manoeuvre, standing up from lying position, and normal relaxed breathing (subject supine). During the tests the electrocardiogram and respiratory pattern were recorded by computer. Beat to beat RR intervals were measured automatically from the electrocardiogram, and from these the results of the tests were calculated. RESULTS: Variance analysis showed significant between subject variability for all tests (p < 0.005), but some tests showed a much smaller relative within subject variability than others. Average repeatability data (within subject SD) for each test were calculated, and included deep breathing sitting (max-min) RR (46 ms), Valsalva ratio (0.17), and lying to standing RR ratio (0.11). These compare with between subject SDs of 65 ms, 0.38, and 0.13 respectively, at mean values of 305 ms, 1.92, and 1.15 respectively. The data highlighted one subject with the poorest repeatability, whose electrocardiogram turned out on closer inspection to be under atrial rather than sinus control at times. Poor repeatability in the other subjects was related to variability in the respiratory pattern, and in the deep breathing test, repeat variability was significantly correlated (r = 0.79) with variability in the respiratory amplitude (p < 0.05). CONCLUSIONS: Repeatability data should be available to each laboratory carrying out autonomic function tests. The data provided in this study could be used as a baseline. Poor repeatability highlights the need to re-examine the test procedures, or the test data from specific subjects. Variability of respiratory pattern is associated with poor repeatability, and so careful instructions on respiration should be given to each subject before the tests.

Adult↗

PubMed1988

Identification of patients at risk of arrhythmia in the Guillain-Barré syndrome.

The frequency of autonomic dysfunction and significant arrhythmia was investigated in a series of 100 patients who presented with an acute idiopathic neuropathy considered to be due to Guillain-Barré syndrome. Eleven of 33 patients requiring ventilation developed serious cardiac rhythm disturbances and seven of these patients died. Approximately 25 per cent of patients had a sinus tachycardia or raised systolic blood pressure and half had reduced sinus arrhythmia indicated by an abnormally low R-R interval variation on deep breathing. Systolic hypertension and reduced R-R interval variation were significantly more common in patients who subsequently developed serious arrhythmias than those who did not. Only those patients that required ventilation developed serious arrhythmias and these were often preceded by wide fluctuations of pulse or blood pressure and transient asystole following tracheal suction.

Adolescent↗

PubMed1996

[A late onset familial amyloidotic polyneuropathy (FAP) with a novel variant transthyretin characterized by a basic-for-acidic amino acid substitution (Glu61-->Lys)].

A 64-year-old man has suffered from intractable diarrhea since January 1990. He noticed numbness and weakness in the distal portion of four extremities in the following several months. His symptoms were gradually progressive. In June 1992, neurological examination revealed mild muscular atrophy and weakness in the proximal and distal portions of four extremities. There were paresthesia and severe impairment of superficial sensations in the lower limbs, lower half of the trunk and upper limbs. All deep tendon reflexes were reduced or absent. Autonomic dysfunctions such as orthostatic hypotension, impotence and diarrhea were evident. On sural nerve biopsy, myelinated fibers showing axonal degeneration were predominantly seen, and densities of both myelinated and unmyelinated fibers were markedly decreased. No amyloid deposits were found in the endoneurium. Amyloid deposition was identified in the gastric mucosa by Congo red staining and immunostaining with anti-transthyretin (TTR) antibody. Edman degradation showed one amino acid substitution of Lys for Glu at position 61 in the TTR-peptides from the serum. Direct DNA sequencing revealed a new point mutation in the 61st codon of TTR gene. The same point mutation of TTR gene was identified in the DNAs from his 67-year-old brother and 63-year-old sister and one of the paternal cousins, a 64-year-old woman, although their clinical symptoms and signs were negative. Clinical features such as late onset of the symptoms and signs and presence of carriers in their sixties in this family are unique and atypical as compared with those of more frequent Val30-->Met FAP families. A variant TTR, characterized by a Glu61-->Lys substitution (a basic-for-acidic amino acid substitution) found in this family, has not been reported in the literature. In the case of the examination of the patients with autonomic and sensory symptoms and signs of unknown etiology, amyloidotic polyneuropathies, including FAP even in the absence of the family history, should be differentiated. When FAP is highly suspected, the combination of family study and DNA analysis of a possible variant TTR is indispensable for the establishment of the diagnosis.

Age of Onset↗