Results Of Autonomic Tests Research Articles

Pulmonary diffusing capacity for carbon monoxide: a marker of depressed hypercapnic drive in Type 1 diabetes mellitus?

Decreased chemosensitivity to hypercapnia, a common finding in Type 1 diabetes mellitus, seems related to autonomic neuropathy. We proposed to verify whether simple neuroautonomic cardiovascular tests or indexes of severity of diabetes and respiratory impairment can identify patients with such a dysfunction, but no clinical evidence of autonomic neuropathy. Forty patients with Type 1 diabetes, 20 with autonomic neuropathy according to the results of a standardized test battery, were studied and compared with 40 normal subjects matched by age and sex. Spirometry and pulmonary diffusing capacity for carbon monoxide were performed. The chemosensitivity to hypercapnia was tested by the rebreathing method. There was no significant difference between patients with and without autonomic neuropathy in chemosensitivity to hypercapnia, as expressed by the ventilation response to increasing end-tidal pressure of carbon dioxide; however, it was lower in the whole group of patients with diabetes than in control subjects (1.71 ± 0.80 vs. 2.45 ± 1.11 l⁻¹ min⁻¹ mmHg, respectively, P=0.002). No significant correlation was found between ventilation response to increasing end-tidal pressure of carbon dioxide and the results of autonomic tests. In patients with diabetes mellitus, the ventilatory response to hypercapnia significantly correlated with pulmonary diffusing capacity for carbon monoxide (Spearman's rho=0.387, P=0.013) and this was the only variable significantly associated with ventilation response to increasing end-tidal pressure of carbon dioxide in a multiple regression model. Chemosensitivity to hypercapnia was depressed in patients with diabetes mellitus, irrespective of autonomic neuropathy, in comparison with control subjects. The correlation with pulmonary diffusing capacity for carbon monoxide suggests that microcirculatory damage might contribute to depress the central chemosensitivity.

Autonomic nerve function in adult patients with cyclic vomiting syndrome

Cyclic vomiting syndrome (CVS) in adults is a disorder characterized by recurrent and stereotypic episodes of severe nausea and vomiting separated by symptom-free periods. Autonomic dysfunction has been a postulated mechanism for the pathogenesis of this disorder in children but has not been explored in adults. Our goals were to investigate autonomic nerve function in adult patients with CVS. The sympathetic nervous system was evaluated through postural changes in heart rate and blood pressure and sympathetic skin response in the hand and foot. The parasympathetic nervous system was tested through heart rate response to deep breathing [expiration/inspiration (E/I)], Valsalva and postural indices (30 : 15 ratio). All patients had a 4-h standard isotope labeled egg beater meal gastric emptying test (GET). Twenty-two adult (18 female), mean age 35 ± 11 (range 19-61 years), who met Rome III criteria for CVS were included. History of migraine headache was reported in three patients. Five (23%) had pediatric onset. Of 21 patients who completed the test, nine patients had 21 abnormalities detected in their autonomic nerve testing profile and the remaining 12 had normal autonomic function results. Orthostatic tachycardia was observed in two (mean heart rate increase 39 beats min(-1)) and a decline in blood pressure (BP) in three patients (mean BP drop 30/14 mmHg). Parasympathetic abnormalities were elicited in six patients with an abnormal response to deep breathing and E/I index <1.25. Sympathetic nerve dysfunction was reported in seven patients with absent sympathetic skin response in the foot and/or hand. Twelve (57%) of CVS group had rapid GET (<50% retention at 1 h). The frequency of abnormal autonomic nerve function was not significantly higher in rapid GET subgroup. (i) Autonomic nerve dysfunction is common in adult CVS patients, being observed in 43% of our cohort; (ii) Sympathetic abnormalities dominate; and (iii) Rapid gastric emptying, present in 57% of patients, did not correlate with autonomic testing results. These new data provide more insight into the pathophysiology of CVS in adults and help explain the spectrum of clinical manifestations observed in this entity.

A neurophysiological approach to the complex organisation of the spine: F-wave duration and the cutaneous silent period in restless legs syndrome

Objective It is generally accepted that F-wave duration (FWD) and the cutaneous silent period (CSP) are influenced by diminished central inhibition. The aim of this study was to diagnose patients of restless legs syndrome (RLS) with the help of FWD and/or CSP parameters. Methods In all, 24 patients with primary RLS were compared with 31 age- and sex-matched controls. The participants were evaluated based on nerve conduction study (NCS), F-wave parameters (minimum, maximum and mean latency; chronodispersion, persistence and duration; and the ratio of the mean FWD to compound muscle action potential (CMAP) duration), CSP (latency, duration and the ratio of lower-extremity (LE) to upper-extremity (UE) duration that is, silent period ratio (SPR)), the expiration to inspiration ratio (E/I) and sympathetic skin response (SSR). Results There were not any significant differences in NCS, E/I or SSR between the patients and controls. However, FWD was prolonged ( P < 0.0001 for UE and LE) and FWD/CMAP duration was increased in upper and lower extremities ( P < 0.001 for UE and P < 0.0001 for LE). Further, CSP latencies in UE ( P = 0.030) and LE ( P < 0.001) were prolonged, and CSP duration and SPR were significantly reduced in the patient group ( P < 0.0001). Conclusions As both NCS and autonomic test results were in the normal range, abnormalities in FWD and CSP parameters were attributed to the dysfunction of different interneuron groups in the spine. Significance The use of FWD and CSP could aid in the diagnosis of RLS patients in whom conventional electrophysiological procedures are ineffective.

Treatment‐induced diabetic neuropathy: A reversible painful autonomic neuropathy

To describe the natural history, clinical, neurophysiological, and histological features, and outcomes of diabetic patients presenting with acute painful neuropathy associated with glycemic control, also referred to as insulin neuritis. Sixteen subjects presenting with acute painful neuropathy had neurological and retinal examinations, laboratory studies, autonomic testing, and pain assessments over 18 months. Eight subjects had skin biopsies for evaluation of intraepidermal nerve fiber density. All subjects developed severe pain within 8 weeks of intensive glucose control. There was a high prevalence of autonomic cardiovascular, gastrointestinal, genitourinary, and sudomotor symptoms in all subjects. Orthostatic hypotension and parasympathetic dysfunction were seen in 69% of subjects. Retinopathy worsened in all subjects. Reduced intraepidermal nerve fiber density (IENFD) was seen in all tested subjects. After 18 months of glycemic control, there were substantial improvements in pain, autonomic symptoms, autonomic test results, and IENFD. Greater improvements were seen after 18 months in type 1 versus type 2 diabetic subjects in autonomic symptoms (cardiovascular p < 0.01; gastrointestinal p < 0.01; genitourinary p < 0.01) and autonomic function tests (p < 0.01, sympathetic and parasympathetic function tests). Treatment-induced neuropathy is characterized by acute, severe pain, peripheral nerve degeneration, and autonomic dysfunction after intensive glycemic control. The neuropathy occurred in parallel with worsening diabetic retinopathy, suggesting a common underlying pathophysiological mechanism. Clinical features and objective measures of small myelinated and unmyelinated nerve fibers can improve in these diabetic patients despite a prolonged history of poor glucose control, with greater improvement seen in patients with type 1 diabetes.

Loss of nocturnal blood pressure fall in various extrapyramidal syndromes

Cardiovascular autonomic dysfunction has frequently been reported in some patients with extrapyramidal syndromes, especially multiple system atrophy (MSA) but also Parkinson's disease (PD). However, there are only few reports on the prevalence of cardiovascular autonomic dysfunction progressive in supranuclear palsy (PSP). Moreover, the relation of detailed cardiovascular testing and easy to assess 24-hour ambulatory blood pressure (BP) is not known. Our study evaluates 24-hour ambulatory BP monitoring in patients with PD, PSP, MSA, and corresponding controls (Con) and relates the findings to the results of comprehensive cardiovascular autonomic testing. Twenty-three patients with PD, 25 patients with PSP, 25 patients with MSA, and 26 corresponding controls were studied by 24-hour ambulatory BP monitoring (ABPM) in comparison to cardiovascular autonomic testing. Patients with PD, PSP, and MSA presented frequently with a pathological nocturnal BP regulation (no decrease or even an increase of nocturnal BP) in comparison to the control group (PD 48%, PSP 40%, MSA 68% vs. Con 8%). In MSA and PD patients, the frequent pathological BP increase during night was closely correlated to orthostatic hypotension. Since loss of nocturnal BP fall is frequent in patients with extrapyramidal syndromes, even if they are free of subjective autonomic dysfunction, we recommend 24-hour ABPM as an easy to perform screening test, especially if detailed autonomic testing is not available. Pathological loss of nocturnal BP fall may account for increased cardiovascular mortality in extrapyramidal syndromes.

Antibody titers predict clinical features of autoimmune autonomic ganglionopathy

Autoimmune autonomic ganglionopathy is a disorder of isolated autonomic failure associated with antibodies to the nicotinic acetylcholine receptor of the autonomic ganglia resulting in severe orthostatic intolerance, syncope, constipation, gastroparesis, urinary retention, dry mouth, dry eyes, blurred vision and anhidrosis. We report the autonomic test results, antibody titers and clinical findings in 8 patients with antibodies to the nicotinic acetylcholine receptor of the autonomic ganglia. There was a sigmoidal relation between the antibody titers and the fall in systolic blood pressure ( r 2 = 0.84). The threshold occurred with antibody titers of ~ 1 nmol/l. Over the linear portion of the sigmoid curve, with antibody titers in the 1–3 nmol/l range, increasing antibody titers resulted in more severe orthostatic hypotension ( r = 0.94, P < 0.001). The saturation point of the sigmoidal relation occurred at ~ 3 nmol/l with drops in systolic blood pressure of ~ 100 mmHg during upright tilt. The antibody titers correlated inversely with the Valsalva ratio ( r= − 0.87, P < 0.001), the 30:15 ratio ( r = − 0.84, P < 0.001) and the expiratory to inspiratory ratio ( r = − 0.67, P < 0.01). Patients with orthostatic intolerance, anhidrosis, constipation, urinary dysfunction, sicca syndrome and pupillary dysfunction had higher antibody titers than subjects that did not ( P < 0.01 in all cases). Autoimmune autonomic ganglionopathy is a clinically heterogeneous disease with variable presentation, particularly in subjects with lower antibody titers. Our data suggest that patients with higher antibody titers have wide spread dysautonomia while those with lower antibody levels may present with, or evolve into, more focal or restricted presentations.

Clinical screening of autonomic dysfunction in multiple sclerosis

Multiple sclerosis (MS) can affect the autonomic nervous system. Although exercise may be beneficial for people with MS, those with autonomic dysfunction may have altered heart rate responses to exercise. We investigated the hypothesis that the pattern of increase in heart rate on commencement of a simple cycle test would be different in those participants with MS who had been shown to have autonomic dysfunction on laboratory testing compared with both control participants and MS participants not exhibiting autonomic involvement. A controlled cohort study with a volunteer sample of 31 adults with MS (26 women, 5 men) with a mean age of 46 +/- 8.00 years (32-60 years), a median Expanded Disability Severity Scale of 3 (1-6) and a mean duration since diagnosis of 10.3 years (0.1-39 years). Thirty-one age-matched, non-disabled, sedentary but healthy adults (26 women, 5 men) with a mean age of 45 +/- 9.5 years (24-57) comprised the control group. Autonomic function was evaluated using continuous heart rate and blood pressure responses to rhythmical deep breathing, the Valsalva manoeuvre, passive postural change and a simple cycle test. There were no significant differences in age, height or weight (p < 0.05) between the two groups or on any of the autonomic test results (p < 0.05). Five participants with MS (16%) had abnormal autonomic function on laboratory testing, two of whom demonstrated an abnormal heart rate response to the cycle test. It is suggested that physiotherapists monitor the heart rate response to a dynamic exercise test in people with MS prior to prescribing an exercise programme to ensure patients' safety. Should the response appear delayed or attenuated, referral for more formal autonomic laboratory testing is recommended.

Effects of pentoxifylline and pentosan polysulphate combination therapy on diabetic neuropathy in type 2 diabetes mellitus

Vascular dysfunction, including impaired perfusion has a pivotal role in the pathogenesis of microvascular complications in diabetes mellitus. Both pentoxifylline (PF) and pentosan polysulphate (PPS) are known to improve microcirculation. Antioxidant and antiproteinuric effects of PF are also known. In a placebo-controlled study, we determined the possible efficacy of PF-PPS combination therapy on diabetic neuropathy and nephropathy in type 2 diabetic patients. Patients in Verum group (n = 77) received PF-PPS infusions (100-100 mg/day) for 5 days. Control diabetics (Placebo group; n = 12) were given only saline infusions. Specialized cardiovascular autonomic reflex tests, vibration threshold values and urinary albumin excretion were assessed before and after therapy. In Verum group, autonomic score, indicating the severity of cardiac autonomic dysfunction, decreased after therapy (p < or = 0.001). Of the reflexes, deep breath and handgrip tests also improved after therapy (p < or = 0.001). Vibration threshold values, an indicator of the loss of sensory nerve function, were increased after therapy (p < or = 0.001). Results of cardiac autonomic tests and vibration threshold values remained unaltered in Placebo group. Majority of patients had normalbuminuria, which was not affected by PF-PPS. In conclusion, short-term PF-PPS therapy was effective on cardiovascular autonomic function and vibration perception, whereas it failed to reduce albuminuria within normal range in type 2 diabetic patients.

Autonomic responses to physiological stressors in women with type 2 diabetes

To compare autonomic function, measured during handgrip (HG) and cold pressor (CP), between obese with and without type 2 diabetes and non-obese women in fasting and post-glucose load states. Twelve obese women with type 2 diabetes (50 +/- 1 years), 15 obese women without type 2 diabetes (48 +/- 2 years), and 12 non-obese women (49 +/- 2 years) participated in this study. Heart rate variability (HRV) was determined during autonomic function tests, conducted in both the fasting state and after a glucose challenge (oral glucose tolerance test-OGTT). Obese women with and without diabetes and non-obese women responded similarly fasted and post-glucose challenge, such that in the fasted state low frequency power normalized (LF(nu)) to total power (TP), log transformed (Ln) low frequency to high frequency ratio (LnLF/HF) and heart rate (HR) significantly increased with the autonomic functional tasks (P < 0.05), whereas HF(nu) significantly decreased with the tasks (P < 0.05). Handgrip elicited a lower LnTP and a higher HR (P < 0.05) when compared to CP in the fasted state. In the glucose challenged state LF(nu), LnLF/HF and HR increased (P < 0.05) and HF(nu) significantly decreased (P < 0.05). Results of autonomic testing did not differ between obese women, with and without diabetes, and non-obese women. The HG test elicited a greater reduction in HRV total power compared to the CP. This suggests that HG may be more useful when examining autonomic function in women with complicated diabetes.

Effects of Statin Treatment on Serum Sex Steroids Levels and Autonomic and Erectile Function

To investigate the effect of statin treatment on serum sex steroid levels, heart rate variability, erectile function, and libido in patients with hyperlipidemia. A total of 74 patients (mean age 44.7 +/- 7.1 years) with hyperlipidemia were enrolled into this study. After a cardiac examination, the serum lipid levels were measured, and the 24-hour Holter monitoring, heart rate variability, and autonomic test results were also evaluated. Erectile function was assessed using the International Index of Erectile Function (IIEF) questionnaire. Later, atorvastatin 40 mg/day was initiated in all patients and used for the subsequent 12 months. All diagnostic tests (cardiac, biochemical, and autonomic and the IIEF questionnaire) were performed again at 6 and 12 months of follow-up. A statistically significant decrease was found in the serum lipid levels at 6 months (P <0.05). In contrast, the average IIEF scores (24.7 +/- 6.4 at baseline) had increased to 25.0 +/- 4.9 and 26.1 +/- 5.9 at 6 and 12 months of follow-up, respectively. Although the parasympathetic activities increased and sympathetic activities decreased with atorvastatin treatment, these changes were not statistically significant (P >0.05). In paired comparison, significant differences were found among the IIEF scores of the three periods (P = 0.013). The difference was more evident after 6 months of treatment (IIEF(1vs2) = 0.475; IIEF(1vs3) = 0.027; IIEF(2vs3) = 0.012). Although improvement in the lipid profile occurred early during the statin treatment, restoration of erectile function appeared later, which could be attributed to the restoration of endothelial functions by lowered serum lipid levels.

Feline dysautonomia in the Midwestern United States: a retrospective study of nine cases.

Dysautonomia of domestic animals is pathologically characterized by chromatolytic degeneration of the neurons in the autonomic nervous ganglia that results in clinical signs related to dysfunction or failure of the sympathetic and parasympathetic nervous systems. The exact cause is unknown. It has a poor prognosis among all species reported and no definitive treatment is available currently. To date, most reported feline cases have occurred in the United Kingdom and Scandinavia. The cases reported here highlight the clinical signs, physical examination findings, and results of autonomic nervous system function testing in nine cats with dysautonomia in the US. Feline dysautonomia is uncommon in the US, but may have a regional prevalence, as is seen in dogs with most cases reported in Missouri and Kansas.

I-123 MIBG cardiac scintigraphy and autonomic test evaluation in multiple sclerosis patients

Autonomic symptoms are common in multiple sclerosis (MS) patients and may cause significant disability. The purpose of this study was to evaluate direct cardiac sympathetic denervation in MS patients with I-123 MIBG cardiac scintigraphy compared with other parasympathetic electrophysiological examinations of autonomic dysfunction. Ten patients with MS and 7 age- and sex-matched control subjects were prospectively evaluated. The neurological deficit and disability stages of the patients were rated according to the Kurtzke Expanded Disability Status Scale (EDSS). Autonomic tests included the R-R interval, Valsalva ratio and standup test. All patients and control subjects had planar and SPECT cardiac scintigraphy with I-123 MIBG injection. Seven MS patients had relapsing-remitting (R-R) type and three had secondary progressive type (SP). A pathological MIBG cardiac washout rate was found in 3/10 MS patients, all of them with SP-MS. The other seven had normal washout rates. No correlation was found between the scan and the individual parasympathetic autonomic test results. I-123 MIBG myocardial scintigraphy may detect direct disturbances of the sympathetic cardiac function in patients with MS in addition to parasympathetic dysfunction tests and can be an important additional means of assessing autonomic pathways. Determination in MS of the co-existence of autonomic dysfunction, especially the cardiac sympathetic involvement in the SP type, may aid in evaluation of disease severity and cardiac function follow-up.

Postural orthostatic tachycardia syndrome: an underrecognized disorder

Postural orthostatic tachycardia syndrome (POTS), a clinical syndrome of orthostatic intolerance characterized by excessive tachycardia and symptoms of cerebral hypoperfusion on standing, is not well recognized in Australia. The aim was to study the clinical symptomatology, results of autonomic testing and outcome in patients with POTS. Sixteen subjects from a tertiary referral centre who met the criteria for POTS were studied between January 2003 and January 2006. Ten of these patients consented to be interviewed using a validated autonomic symptom questionnaire. Heart rate responses to deep breathing and the Valsalva manoeuvre were measured using Colin BP-508 machine (WR Medical Electronic Co., Stillwater, MN, USA). Tilt studies were carried out for 10 min to 80 degrees of head-up tilting. Patient outcome was assessed as functionally normal, able to stand 30 min without symptoms, able to work and carry out recreational activities or worse on follow up. The mean age of 10 subjects was 24.9 +/- 6.8 years, six being women. The mean duration of symptoms was 70.7 months (range 3-228 months). The common presenting orthostatic symptoms were light-headedness (100%), palpitations (90%), pallor (90%), weakness (80%) and clammy skin (80%). The mean heart rate increment during the tilt study was 51.7 +/- 14.3 b.p.m. The mean duration of follow up was 8.9 months (range 1-16 months). Only five patients were functioning normally at the follow-up visit. POTS is an underrecognized but persistent autonomic disorder in young patients with a variety of symptoms and variable outcome.

Autonomic Abnormalities in Cyclic Vomiting Syndrome

Although cyclic vomiting syndrome (CVS) is associated with migraine, and migraine in turn is associated with orthostatic tachycardia, few studies have explored the association of CVS and autonomic dysfunction. We describe the results of autonomic testing in 6 children with characteristic CVS. All patients fully met the established criteria for the diagnosis of CVS, were well hydrated, and were beyond their episode of vomiting. We performed 3 tests of cardiovascular function and 1 sudomotor test, using standard previously published methods. The findings were surprisingly uniform, with normal cardiovascular responses to deep breathing and to the Valsalva maneuver in all patients, a significant increase in heart rate (>30 beats per minute) with tilt testing, and a vasodepressor tendency in 2 patients. Interestingly, abdominal pain occurred at blood pressure nadir in both these patients and in a third patient without the vasodepressor findings but who described syncope clinically. Sudomotor test results were abnormal in all 6 patients, with reduced responses in 5 of 6 and exaggerated responses in the 6th. All 6 patients reported a personal or family history of migraine headaches. CVS is associated with remarkably uniform primarily sympathetic autonomic dysfunction, affecting mainly the vasomotor and sudomotor systems, and compatible with an underlying autonomic neuropathy. The occurrence of symptoms during tilt testing in half the patients suggests that these findings may play a true pathophysiologic role. A vagally modulated sympathetic effect is postulated as the best mechanistic model to account for all current physiologic data on cyclic vomiting and gastroparesis.

Oesophageal motility disorders in type 1 diabetes mellitus and their relation to cardiovascular autonomic neuropathy

The relationship between cardiovascular autonomic neuropathy (CVAN) and oesophageal dysfunction in diabetes mellitus has not been well established because reports are contradictory. The aim of this study was to assess oesophageal function and its correlation with CVAN in type 1 diabetic patients without oesophageal symptoms. Forty-six type 1 diabetic patients without oesophageal symptoms (DG) and 34 healthy volunteers (CG) were studied. Both groups underwent CVAN tests and oesophageal manometry and pH-metry. Differences between groups regarding results of cardiovascular autonomic tests and oesophageal studies were statistically analysed. Compared with the CG, the DG group showed insufficient lower oesophageal sphincter (LOS) relaxation and a higher percentage of simultaneous waves (P < 0.01). Patients with CVAN (n = 22) showed a higher prevalence of pathological simultaneous contractions (>10%), and the prevalence of simultaneous waves related to the degree of autonomic neuropathy was: 9% of patients without CVAN, 7% of those suspected to have it and 50% of patients with CVAN (P < 0.001). Factors associated with the presence of pathological simultaneous waves (>10%) were the presence of CVAN and duration of diabetes (P < 0.05, logistic regression analysis). Increase in simultaneous waves and impaired relaxation of LOS are more frequent in diabetic patients with CVAN.

Long-term clinical evaluation in patients with Parkinson's disease and early autonomic involvement

Objective To evaluate in a prospective longitudinal study the evolution of functional disability and the response to dopaminergic therapy in PD patients with and without autonomic involvement. Methods Sixty untreated consecutive patients with PD underwent autonomic cardiovascular function evaluation using the five autonomic tests of Ewing. An integrated index (Autonomic Score=AS), taking in account the results of all subtests, was calculated. Patients were treated with pergolide and bromocriptine during a 5-year follow-up until the level of functional disability was sufficient to warrant the initiation of levodopa therapy. Results Results of autonomic testing were compared with those of a group of age-matched healthy subjects. A value of AS>2 was considered as indicative of autonomic failure. Eighteen patients with PD (35%) showed AS>2 (autonomically impaired group=AI), the remaining 33 (65%) had AS<2 (nonautonomically impaired group=non-AI). During the follow-up levodopa was added to the treatment regimen of 10/18 (55%) patients in AI group, and 6/33 (18%) patients in non-AI group ( p<.01). Conclusions The increased occurrence of levodopa adjunct in autonomically impaired PD suggests that there is a more rapid deterioration of functional performance in parkinsonian patients with early autonomic involvement.

Cough-Induced Hemiplegic Migraine with Impaired Consciousness in Cystic Fibrosis

The coughing paroxysms of patients with cystic fibrosis may occasion neurological symptoms. Although cough syncope is well-known, and is associated with headache and paralysis, a migrainous mechanism has not been reported. We reviewed the medical records, autonomic testing results, and responses to treatment in two cystic fibrosis patients with similar presentations of cough-induced impairment of consciousness followed by headache and paralysis. A 24-year-old woman and an unrelated 38-year-old man, both with cystic fibrosis, developed post-tussive neurologic deficits. Both patients reported infrequent dramatic spells, always preceded by major hemoptysis, and associated with left-sided paralysis, transient blindness, nausea, and severe pulsating headaches. Autonomic testing demonstrated only postural tachycardia and a near-vasodepressor episode in the woman, and mild, generalized sympathetic dysfunction in the man. Treatment for presumptive migraine with aura with verapamil nearly eradicated symptoms in both patients. Discontinuation of verapamil in the woman was associated with symptom recurrence and a stroke, with significant persistent residual left hemiparesis. In conclusion, cough-induced neurologic deficits were previously reported with cystic fibrosis, without clear understanding of the mechanism of impairment of consciousness. Based on the hemiparesis, nausea, and throbbing headache, which repeatedly followed the events in both patients, and based on the response to verapamil, we hypothesize a migrainous mechanism in both of our patients. The pathophysiology that links the hemoptysis to the spells deserves further investigation.

Clinical Characteristics of Patients with Multiple System Atrophy in Singapore

Introduction: Our study aimed to describe the clinical features of multiple system atrophy (MSA) in Singapore and verify its diagnosis using the consensus statement in the diagnosis of MSA. Materials and Methods: All patients suspected to have MSA between 1995 and March 2005 were identified from the Movement Disorders database and the autonomic function testing results. The medical records were reviewed using a standardised data collection form. The diagnosis of MSA was verified using the consensus statement. Disease progression was evaluated using 2 pre-determined events: aid-requiring walking and wheelchair use. Results: Seventy-two per cent (33/46) fulfilled the consensus statement. There were 85% Chinese, 9% Malays, and 6% Indians. The mean age at onset of the disease was 60 ± 10 years. We found a predominance of males (M:F = 1.5:1) as well as MSA-C cases (67%). The most common initial presenting features were parkinsonism and cerebellar signs (27% each). Abnormal neuroimaging was seen in 29 patients (91%). Autonomic function testing was abnormal in 58% (7/12). The risk for aid-requiring walking and wheelchair use at 3 years from onset of the disease was 31% and 17%, respectively. By 5 years, this had increased to 45% and 30%, respectively. There was no difference in the events rate between MSA subtypes. Conclusions: The clinical characteristics of MSA in Singapore are presented. Our study revealed a predominance of MSA-C patients as well as a later age at onset of disease and longer median time to aid-requiring walking and wheelchair use compared to Japanese patients.

Autonomic dysfunction in ALS: A preliminary study on the effects of intrathecal BDNF

This pilot study aimed at exploring the effects of intrathecally administered brain derived neurotrophic factor (BDNF) on autonomic functions in patients with ALS. A battery of autonomic sympathetic and parasympathetic tests was performed at baseline and after nine months of treatment in 10 ALS patients participating in a double-blind placebo-controlled phase II/III study of intrathecally administered BDNF. Results of patients treated with BDNF (25 or 150 microg/day) were compared to those receiving placebo. Sudomotor function and blood pressure response to handgrip significantly worsened during the treatment period (55.4+/-26.1 vs. 38.9+/-23.9 g/m(2)h, p<0.05; 20+/-6 vs. 13+/-4 microHg, p<0.05) whereas other sympathetic and all parasympathetic function tests only tended to be more abnormal at follow-up. Serum norepinephrine levels increased significantly during the nine-months observation period. The results of autonomic function tests were not different between patients treated with BDNF and placebo, but norepinephrine levels were higher in the BDNF group. We conclude that autonomic nervous system function deteriorates along with poorer motor performance independently from treatment with BDNF. The elevation of norepinephrine levels might reflect a non-specific up-regulation, and its association with BDNF an autocrine effect.

Autonomic related vertigo.

To demonstrate clinical evidence that vestibular symptomatology can occur in relation to autonomic dysfunction. Characterization of clinical findings and treatment response would then allow autonomic related vertigo to be differentiated from other vertiginous conditions that present in a like manner. This was a retrospective review of 113 patients that described symptoms consistent with spontaneous, rotational vertigo and autonomic dysfunction. Vestibular, otologic, and autonomic symptoms are presented along with the results of audiologic, orthostatic, and autonomic testing. Medical management included fluid loading, dietary changes, exercise, and patient education. Treatment results were analyzed according to the effectiveness in control of vestibular and otologic symptoms. Results were compared with a control group that demonstrated a similar vestibular and otologic presentation without autonomic symptomatology. All patients described spontaneous, rotational vertigo, with complete or substantial vertigo control obtained in 93 (85%) of 110 patients. Postural vertigo and distinct lightheadedness were also documented in 53% and 97% of cases, respectively. Vertigo failed to improve or worsened with prior treatment of low sodium diet or diuretic in 53 (91%) of 58 cases. Vertigo improvement was subsequently achieved in 48 (86%) of 56 cases with an autonomic treatment regimen. Long-term vertigo control was obtained in 56 (88%) of 64 patients followed for at least 18 months. Tinnitus was reported in 97 (86%) patients, aural fullness in 93 (82%) patients, and subjective hearing loss (HL) in 46 (41%) of 111 cases. Bilateral tinnitus and aural fullness occurred in 65% and 63%, respectively. Tinnitus improved with treatment in 56 (67%) of 84 patients, whereas aural fullness improved in 59 (74%) of 80 patients. Autonomic symptoms included palpitations in 103 (91%) patients, chronic fatigue in 102 (90%) patients, cold extremities in 91 (81%) patients, and previous fainting in 72 (64%) patients. A history of mitral valve prolapse was documented in 51 (45%) of cases and demonstrated with echocardiogram in 68 (93%) of the 73 patients tested. Audiologic testing was normal in 104 (95%) of 109 patients, and electrocochleography was abnormal in 42 (40%) of 105 patients. Orthostatic blood pressure and heart rate testing met the criteria for orthostatic hypotension in 16 (15%) of 104 patients. Autonomic testing was obtained in 34 cases, with orthostatic intolerance demonstrated in 33 (97%) patients and orthostatic hypotension demonstrated in 13 (38%) patients. Overall, orthostatic hypotension was documented through combined testing results in 23 (21%) of 107 patients. Vertigo was reproduced during autonomic testing in 17 (77%) of 22 patients, and otologic symptoms were reproduce in 9 (47%) of 19 patients. Comparison of the study population with a control group without autonomic symptoms revealed statistically significant differences in orthostatic testing and treatment results. There was no statistical difference noted in findings between patients of this study that demonstrated or failed to demonstrate orthostatic hypotension. There is a subgroup of patients with spontaneous vertigo who also demonstrate symptoms and findings consistent with poor autonomic regulation. These patients report vertigo improvement with a treatment strategy that aims to improve autonomic dysfunction through expansion of effective circulating volume. Clinical findings and treatment results of this study suggest an underlying autonomic influence in the production of vertigo and otologic symptoms.