Cortical T2 signal shortening in amyotrophic lateral sclerosis is not due to iron deposits.

Signal shortening of the motor cortex in T2-weighted MR images is a frequent finding in patients with amyotrophic lateral sclerosis (ALS). The cause of signal shortening in ALS is unknown, although iron deposits have been suggested. To test this hypothesis, we acquired T2*-weighted gradient-echo (GRE) MR images in addition to T2-weighted turbo spin-echo in 69 patients with ALS. Signal shortening in T2-weighted images was found in 31 patients. In T2*-weighted GRE images, only three patients had signal shortening. One patient with additional bifrontal haemorrhage had frontal but no motor cortex signal shortening. Iron deposits do not cause cortical signal shortening in patients with ALS predominantly. Other factors are presumably more important in the generation of cortical T2 shortening in ALS.

Effects of lower body negative pressure on cardiac and vascular responses to carotid baroreflex stimulation.

The aim of this study was to assess carotid baroreflex responses during graded lower body negative pressure (LBNP). In 12 healthy subjects (age 29+/-4 years) we applied sinusoidal neck suction (0 to -30 mmHg) at 0.1 Hz to examine the sympathetic modulation of the heart and blood vessels and at 0.2 Hz to assess the effect of parasympathetic stimulation on the heart. Responses to neck suction were determined as the change in spectral power of RR-interval and blood pressure from baseline values. Measurements were carried out during progressive applications (0 to -50 mmHg) of LBNP. Responses to 0.1 and 0.2 Hz carotid baroreceptor stimulations during low levels of LBNP (-10 mmHg) were not significantly different from those measured during baseline. At higher levels of LBNP, blood pressure responses to 0.1 Hz neck suction were significantly enhanced, but with no significant change in the RR-interval response. LBNP at all levels had no effect on the RR-interval response to 0.2 Hz neck suction. The unchanged responses of RR-interval and blood pressure to neck suction during low level LBNP at -10 mmHg suggest no effect of cardiopulmonary receptor unloading on the carotid arterial baroreflex, since this LBNP level is considered to stimulate cardiopulmonary but not arterial baroreflexes. Enhanced blood pressure responses to neck suction during higher levels of LBNP are not necessarily the result of a reflex interaction but may serve to protect the circulation from fluctuations in blood pressure while standing.

Clonidine improves postprandial baroreflex control in familial dysautonomia.

BACKGROUND: Patients with familial dysautonomia (FD) frequently experience hypertensive crises after gastrostomy feeding. The central alpha2-agonist clonidine attenuates feeding-induced crises. The aim of this study was to assess the effect of clonidine on cardiovascular autonomic modulation and particularly baroreflex sensitivity in familial dysautonomia after gastrostomy feeding. MATERIAL AND METHODS: In nine patients, we monitored the RR-interval and systolic blood pressure at supine rest before (baseline 1) and after gastrostomy feeding (GF1). One day later, recordings were repeated after clonidine intake (baseline 2, GF2). We determined spectral powers of RR-interval and systolic blood pressure in the low- (LF) and high-frequency range (HF). Sympathovagal balance was determined from the LF/HF ratio of RR-interval. Baroreflex sensitivity was assessed from the alpha-index of systolic blood pressure and RR-interval. RESULTS: Gastrostomy feeding decreased RR-interval, while systolic blood pressure remained stable. Clonidine induced higher RR-intervals before and after gastrostomy feeding but decreased systolic blood pressure at baseline only. Gastrostomy feeding decreased HF-power of RR-interval significantly without clonidine, but only slightly after premedication. Clonidine increased the HF-power of RR-interval slightly at baseline and significantly after gastrostomy feeding. Gastrostomy feeding increased the LF/HF ratio without clonidine only. Clonidine decreased the LF/HF ratio at baseline and after gastrostomy feeding. Gastrostomy feeding did not change baroreflex sensitivity, but baroreflex sensitivity was higher at visit 2 than visit 1. CONCLUSIONS: In familial dysautonomia, clonidine augments baroreflex sensitivity and parasympathetic modulation. The resulting cardiovascular stabilization might attenuate feeding-induced crises.

Effects of age on the cardiac and vascular limbs of the arterial baroreflex.

BACKGROUND: Healthy ageing has several effects on the autonomic control of the circulation. Several studies have shown that baroreflex-mediated vagal control of the heart deteriorates with age, but so far there is little information regarding the effect of ageing on sympathetically mediated baroreflex responses. The aim of this study was to assess the effects of ageing on baroreflex control of the heart and blood vessels. MATERIALS AND METHODS: In 40 healthy volunteers, aged 20-87 years, we applied oscillatory neck suction at 0.1 Hz to assess the sympathetic modulation of the heart and blood vessels and at 0.2 Hz to assess the effect of parasympathetic stimulation on the heart. Breathing was maintained at 0.25 Hz. Blood pressure, electrocardiographic RR intervals and respiration were recorded continuously. Spectral analysis was used to evaluate the magnitude of the low-frequency (0.03-0.14 Hz) and high-frequency (0.15-0.50 Hz) oscillations in the RR interval and blood pressure. Responses to neck suction were assessed as the change in power of the RR interval and blood pressure fluctuations at the stimulation frequency from baseline values. RESULTS: Resting low- and high-frequency powers of the RR interval decreased significantly with age (P < 0.01). However, the low-frequency power of systolic blood pressure did not correlate with age. Spontaneous baroreflex sensitivity (alpha-index) showed a significant inverse correlation with age (r = -0.46, P < 0.05). Responses of the RR interval and systolic blood pressure to 0.1 Hz neck suction stimulation were not related to age, however, the RR interval response to 0.2 Hz neck suction declined significantly with age (r = -0.61, P < 0.01). CONCLUSIONS: These results confirm an age-related decrease in cardiovagal baroreflex responses. However, sympathetically mediated baroreflex control of the blood vessels is preserved with age.

Neuropathy is a major contributing factor to diabetic erectile dysfunction.

Erectile dysfunction (ED) in diabetes is multifactorial. So far, the impact of neuropathy has not been well determined. This study was performed to assess the frequency of abnormal neurophysiological tests in patients with ED due to diabetes compared to patients with ED due to nondiabetic neuropathies in order to estimate the contribution of neuropathy in diabetic ED. Forty-nine men with ED were studied. We classified ED as 'diabetic', 'neuropathic' or 'ED of other origin'. 26.6% of the men fulfilled the criteria of diabetic ED, 42.9% had neuropathic ED. In every patient history taking, a questionnaire focusing on autonomic symptoms other than ED, clinical examination, nerve conduction studies (NCS), sphincter ani electromyography (EMG), heart rate variability testing (HRV) and quantitative sensory testing (QST) was performed. Vascular function was assessed by the intracavernosal prostaglandin E1 (PGE1) injection test. The frequency of abnormal results in diabetic and neuropathic patients was compared. Vascular function was abnormal in only one patient with diabetic ED and three patients with neuropathic ED. Both groups had similar frequencies of autonomic symptoms other than ED (64% in diabetic vs. 64% in neuropathic patients), abnormal EMG (33% vs. 40%) and abnormal QST (vibratory perception 83% vs. 84%, cold perception 9% vs. 19%, warm perception 42% vs. 43%). Abnormal clinical findings (50% vs. 33%), NCS (75% vs. 50%) and HRV (39% vs. 25%) were slightly, but not significantly more frequent in men with diabetic ED than neuropathic ED. The tests indicating neuropathy showed abnormalities in men with diabetic ED as frequently as in men with neuropathic ED. Some tests even suggested neuropathy more often in diabetic than in neuropathic ED. The findings support the hypothesis that neuropathy contributes significantly to the pathophysiology of ED in diabetes mellitus.

MRI-FLAIR images of the head show corticospinal tract alterations in ALS patients more frequently than T2-, T1- and proton-density-weighted images.

In some patients with amyotrophic lateral sclerosis (ALS), T2-weighted and proton-density-weighted magnetic resonance imaging (MRI) shows hyperintense or hypointense signals at the corticospinal tract. Fluid-attenuated inversion recovery (FLAIR) sequences increase the sensitivity of MRI to detect cortical and subcortical tissue changes. In 31 ALS patients and 33 controls, we studied the frequency and the extent of signal abnormalities in FLAIR images compared to T2-, T1- and proton-density-weighted images. Hyperintense signals at the corticospinal tract were significantly more frequent in FLAIR images than in all other tested sequences. In FLAIR images of ALS patients only, distinct hyperintense signals at the subcortical precentral gyrus (five patients), the centrum semiovale (eight patients), the crus cerebri (nine patients) and the pons (four patients) as well as mild hyperintense signals in the medulla oblongata (three patients) were seen. More frequently, but not exclusively in ALS patients, FLAIR images showed mild hyperintense signals at the subcortical precentral gyrus (15 patients vs. 1 control). Quantitative analysis confirmed the significant difference between ALS patients and controls at the subcortical precentral gyrus in FLAIR images. In T1-weighted images, the corticospinal tract at the capsula interna was hypointense in significantly more controls than ALS patients. Also this difference was confirmed in the quantitative analysis. Similar to previous results, MR image alterations did correlate poorly to clinical data of upper motor neuron affliction.MR images of the head, including FLAIR images, provide additional information regarding corticospinal tract involvement in ALS patients. Because of an overlap with physiological findings, they have to be interpreted cautiously, with the exception of hyperintense signals at the subcortical precentral gyrus.

[Survival with artificial respiration at home. An open, prospective study on home ventilation for neuromuscular diseases, in particular, the situation of ALS patients]. / Uberleben mit Heimbeatmung. Eine offene, prospektive Untersuchung zur Heimbeatmung bei neuromuskulären Erkrankungen unter besonderer Berücksichtigung der Situation von ALS-Patienten.

A growing number of patients with neuromuscular disease have been treated with home mechanical ventilation during the past 15 years. We prospectively examined the long-term effects and complications of this method, particularly with regard to noninvasive positive pressure ventilation (NPPV). Thirty-one patients with amyotrophic lateral sclerosis (ALS, n = 20) or other slowly progressive neuromuscular diseases (NMD, n = 11) were observed for 17,517 home ventilation days (almost 48 ventilation years). The mean observed ventilation time was 565 days (min/max: 30/2930). Twenty-five patients were ventilated noninvasively with different masks. The calculated mean survival with NPPV ventilation (criteria: death, tracheostomy, or patient deciding to break off) was 2052 (SE: +/- 317.8) days in the NMD group, 248 days (+/- 35.7) for ALS patients without bulbar symptoms, and 82 days (+/- 27.4) with bulbar paralysis. Complications with the need for intervention were observed six times more frequently with ALS than with NMD. NPPV is effective for years in patients with slowly progressing NMD. Those ALS patients without bulbar symptoms can profit for up to a year from NPPV, while those with bulbar paralysis can have some symptom relief. Complications of every kind are much more frequent in ALS patients.

Abnormal vasoreaction to arousal stimuli--an early sign of diabetic sympathetic neuropathy demonstrated by laser Doppler flowmetry.

Early diagnosis of diabetic autonomic neuropathy contributes to the prevention of serious complications and improves the prognosis of patients with diabetes. Common tests of peripheral autonomic function are the quantitative sudomotor axon reflex test or the sympathetic skin response (SSR). Quantitative sudomotor axon reflex test is quantifiable but technically demanding. Sympathetic skin response cannot be quantified easily. To study whether measurement of skin vasomotion is suited to assess early sympathetic peripheral neuropathy, we monitored skin blood flow at the index finger pulp using laser Doppler flowmetry before and after electrical stimulation. We assured that the stimulus was sufficient to elicit an efferent sympathetic response by monitoring palmar SSR ipsilateral to the flow measurement. In 21 diabetic patients with at least stage one polyneuropathy and 21 age-matched controls, SSR was recorded from one palm and sole following electrical stimulation at the contralateral wrist. Sympathetic skin response was present at the palms in all patients and controls and absent at the sole of two patients only. Eight patients (38.9%) had abnormal SSR, with absent plantar responses in two patients, prolonged plantar latencies in six patients, and prolonged volar SSR latencies in two patients. Skin blood flow responses were more often abnormal (46.1%) than SSR (P < 0.05), responses were delayed in two patients and absent in another 8 patients. Skin blood flow retest reliability was high with a repeatability coefficient of 10.64% in controls and 12.34 % in patients. Skin blood flow monitoring after sympathetic stimulation provides a reproducible parameter of sympathetic vasomotor control and complements the diagnostic value of SSR testing.