Faculty Bibliography

Several studies suggest hemispheric lateralization of autonomic cardiovascular control. There is controversy regarding which hemisphere dominates sympathetic or parasympathetic activity. Hemispheric influences on baroreflex sensitivity (BRS) have not yet been evaluated. To determine hemispheric autonomic control in epilepsy patients, we assessed cardiovascular and baroreflex modulation before and during hemispheric inactivation. For 15 patients with drug-refractory epilepsy, we analyzed autonomic heart rate (HR) and blood pressure (BP) modulation and BRS before and during left and right intracarotid amobarbital procedure (IAP). After Blackman-Tukey spectral analysis, we calculated the low-frequency (LF: 0.04-0.15 Hz) and high-frequency (HF: 0.15-0.5 Hz) power of HR and BP as well as BRS as the LF transfer function gain between BP and HR. Right hemispheric inactivation induced a significant decrease of BP and an increase of HF power of HR and BP (p < 0.05). Left inactivation increased HR, BP, and LF power of both signals and decreased BRS by nearly 30% (p < 0.05). The results confirm previous IAP studies showing sympathetic lateralization in the right hemisphere and, moreover, demonstrate parasympathetic predominance and up-regulation of BRS in the left hemisphere. In epilepsy patients, unilateral electrical activity might derange autonomic balance between both hemispheres and contribute to cardiovascular dysregulation and sudden fatalities

OBJECTIVE: First, to evaluate the role of typical intensive care-related conditions like sepsis, prolonged ventilation, drug effects and metabolic disorders in the pathogenesis of critical illness polyneuropathy (CIP); second, to investigate the possible significance of patient serum neurotoxicity assessed by an in vitro cytotoxicity assay with respect to CIP development. DESIGN: Prospective study. SETTING: Neurological intensive care unit. PATIENTS AND PARTICIPANTS: Twenty-eight patients who were on mechanical respiratory support for at least 4 days during a 21-month study period. RESULTS: Diagnosis of CIP was established by clinical and electrophysiological examination in 16 (57%) of 28 patients. Patients were investigated on days 4, 8 and 14 of mechanical ventilation. Two of 16 CIP patients had clinical signs of polyneuropathy at initial examination. Factors that correlated significantly with the development of CIP were: the multiple organ failure score on day 8 of ventilation, the total duration of respiratory support, the presence of weaning problems and the manifestation of complicating sepsis and/or lung failure. The in vitro toxicity assay showed serum neurotoxicity in 12 of 16 CIP patients. Electrophysiological investigations yielded false positive results of the toxicity assay in six patients (not developing CIP) and false negative results in four patients (developing clinical and electrophysiological signs of CIP). Statistical analysis did not reveal a significant correlation between the diagnosis of CIP and the finding serum neurotoxicity. CONCLUSION: The results support the hypothesis of a multi-factorial aetiopathogenesis of CIP. We observed serum neurotoxicity in the majority of CIP patients, indicating the possible involvement of a so far unknown, low-molecular-weight neurotoxic agent in CIP pathogenesis

The objective of the present study was to evaluate the influence of posture on the responses of blood pressure (BP) and heart rate (HR) to the Valsalva manoeuvre (VM). Neurohumoral activation, as well as changes in intravascular and intracardiac volumes and pressures, are well known effects of orthostatic stress. These changes are likely to have significant effects on cardiovascular reflexes, such as the response to the VM. However, the influence of posture on the VM has not been intensively evaluated, except for a few studies involving small sex- and age-selected case series. We therefore investigated the effects of posture on the VM in a larger non-selected group of healthy control subjects. In 19 healthy volunteers (ten female/nine male; age range 20-72 years, mean age 43 years), two reproducible VMs (40 mmHg; 15 s) were performed after 10 min of supine rest, 10 min of sitting and 10 min of standing. HR and BP were monitored continuously. End-diastolic volume, total peripheral resistance and cardiac output were calculated at baseline for each position. We found that assuming an upright position resulted in increases in total peripheral resistance and HR, accompanied by decreases in end-diastolic volume and cardiac output. The fall in BP during early phase II and the BP overshoot during phase IV were clearly more pronounced with increasing orthostatic stress, whereas the rise in BP during late phase II remained unchanged; pulse pressure was more compressed during phase II, but higher during phase IV. The Valsalva ratio was not significantly affected, but baroreflex gain (calculated from early phase II) was significantly decreased in the upright position. While a reduced late phase II was observed on one occasion in each of the lying and sitting positions, three abnormal responses were observed during standing. We conclude that posture has a significant influence on BP responses to the VM, probably resulting from changes in the intrathoracic blood volume. Standing results in a lower rate of 'flat-top' responses, but also seems to reduce the specificity of this test. Sympathetic activation in the upright position seems to blunt baroreflexes, leading to similar HR responses in spite of larger changes in BP

In the lost years, the multifocal motor neuropathy (MMN) has been characterized as an immunomediated neuropathy. Clinically MMN might be misdiagnosed as amyotrophic lateral sclerosis (ALS). The differential diagnosis, however, is important, as there is an effective therapy available for MMN-in contrast to ALS. The differentiation depends on the demonstration of characteristic focal conduction blocks in motor nerves in MMN. Other electrophysiological measurements such as peripheral nerve conduction studies and electromyography ore less useful. Another typical finding in MMN are high titers of specific anti-GM1-antibodies in the serum. This report summarizes diagnostic and differential diagnostic criteria and therapeutical options of MMN. $$:

Guilloin-Barre syndrome (GBS) is the most common cause of acute generalised neuropathy. In Europe, 70% of the GBS patients develop an acute inflammatory demyelinating polyneuropathy (AIDP). Demyelinisation of the nerves accounts for a slowing down in nerve conduction, characterized by prolonged distal motor latencies, decreased nerve conduction velocities, potential dispersion and prolonged F-wave-latency, as well as conduction blocking, characterized by conduction blocks, decreased amplitudes of compound muscle action potentials and diminished recruitment of motor units in the electromyography. Demyelinisation often occurs in distal and proximal nerve regions. Sensory nerve abnormalities are less frequent and occur later in the course of the disease. Acute motor axonal neuropathy (AMAN) and acute motor-sensory axonal neuropathy (AMSAN) are characterized by decreased potential amplitudes and, later in the course of the dis-ease, signs of acute denervation in EMG. In contrast, in chronic demyelinating polyneuropathy (CIDP) there are frequently generalised demyelinations as well as secondary axonal alterations. In the early phase of the disease, electrophysiologic signs may be discrete. According to the American Academy of Electrodiagnostic Medicine (AAEM) the presence of demyelinating nerve conduction study abnormalities in at least two nerves in regions not typical for compressive mononeuropathies, preferably in both an arm and a leg, or a limb and the face are very suspicious for Guillairi-Barre syndrome. For a more precise staging of the course of the disease, the criteria of the Dutch Guillain-Barre study group (for GBS) and the criteria of Alsbury and Cornbloth (for CIDP) are more appropriate. $$:

The aim of the current pilot study was to establish a procedure that would allow the investigation of microcirculatory changes in the oral cavity. The authors studied the effects of painful stimulation using dry ice (CO2). To investigate potential regional differences in the change of blood flow, recordings were made for the tongue and at the mucosa of the hard palate, lip, and oral vestibule. The authors investigated 26 patients divided into groups of younger subjects (10 men, 3 women; age range 21-31 y) and older patients (2 men, 11 women; age range 54-74 y). Mucosal blood flow (mBF) was obtained at the hard palate, at the tip of the tongue, on the midline of the oral vestibule, and at the lip. Measurements were made during rest and for 2 minutes after application of dry ice for a 10-second duration, using a pencil-shaped apparatus. Blood pressure, heart rate, cutaneous blood flow, transcutaneous partial pressure of carbon dioxiode (PCO2) and partial pressure of oxygen (PO2) were recorded. Mucosal blood flow increased at all sites in response to application of dry ice (p <0.001), with peak flow at 0.5 minute to 1.5 minutes after onset of stimulation. During the 1.5 minutes to 2 minutes, blood flow decreased at all measurement sites with a tendency to return to baseline. Heart rate, blood pressure, pCO2, PO2, and cutaneous blood flow did not show significant changes. Overall, responses in older patients showed more variance when compared with younger patients. Stimulation by dry ice appears to be an effective, noninvasive, and tolerable means to investigate mucosal blood flow at different mucosal sites. Preliminary data indicate different levels of responsiveness to painful cold stimulation at different sites on the oral and perioral mucosa; particularly, mucosal blood flow response at the tongue was least pronounced. Therefore, assessment of stimulated mucosal blood flow appears to be a promising tool to investigate the pathophysiology of a number of neurologic symptoms, eg, the burning mouth syndrome

Cerebrovascular autoregulation assures constancy of cerebral perfusion despite blood pressure changes, as long as mean blood pressure remains in a range between 50-170 mmHg. Static and dynamic myogenic mechanisms dampen sudden blood pressure changes. Neurogenic influences of sympathetic, noradrenergic fibers modulate primarily proximal, large diameter segments of cerebral arteries, but also small 15-20 microns diameter vessels. Parasympathetic, vasodilating impulses are of less influence. Monoaminergic brainstem centers such as the dorsal raphe nucleus, locus coeruleus or nucleus reticularis pontis oralis also influence vessel tone. Metabolic, local parenchymal and endothelial substances have major impact on cerebral vessel tone. Particularly important are nitric oxide, calcitonin gene related peptide, substance P, endothelin, potassium channels and autocoids such as histamine, bradykinin, arachidonic acid, prostanoids, leucotrienes, free radicals or serotonin. The clinical examination of autoregulation is mostly based on brief blood pressure changes induced by drugs such as angiotensin, phenylephrine or sodium nitroprusside, or by challenge maneuvers. Frequently, blood pressure is challenged by a tilt-table maneuver, the 'leg-cuff'-method according to Aaslid, or a Valsalva maneuver. The analysis of coherence and phase relation between spontaneous or metronomic breathing modulation of blood pressure and brain perfusion also assesses autoregulatory function. Cerebral blood flow is determined by means of transcranial Doppler sonography, mostly of the proximal segment of the mid-cerebral artery. There is some controversy whether a decrease of cerebral blood flow velocity measured at this segment indicates vasodilatation at the insonated segment or reflects blood flow reduction due to decreased perfusion of down-stream vessel segments. Various clinical and animal studies are presented demonstrating diameter constancy of the insonated mid-cerebral artery segment and thus indicating that slowing of mid cerebral artery blood flow velocity as assessed by transcranial Doppler sonography is due to a decrease of down-stream perfusion. Direct, intraoperative measurements of vessel diameter confirm this conclusion

Cerebrovascular hemodynamics during physical stress have been sparsely investigated, mostly through risky invasive techniques. The aim of this study was to determine the effect of ergometer stress on cerebrovascular hemodynamics in humans using the non-invasive and thus clinically-applicable method of transcranial Doppler sonography (TCD) combined with simultaneous non-invasive measurements of cardiovascular parameters. In eighteen healthy subjects (six women, twelve men; 29.3+/-4.6 years old) left midcerebral artery blood flow velocities (CBFVs) were continuously monitored using TCD during 3 min at rest, 3 min during ergometry and 3 min recovery. Simultaneously, systolic, diastolic, mean CBFVs, pulsatility index (PI), heart rate, beat-to-beat blood pressure (BP) and transcutaneous p(CO(2)) were measured. The subjects were supine with elevated trunk. Ergometry was performed by pedalling a Muhe-ergometer. In eight volunteers, the procedure was repeated within the next day to test the repeatability of the results. Heart rate increased significantly during ergometry (from 65.2+/-11 to 105. 3+/-12.3/min; P<0.05). The systolic BP increased significantly slightly later during ergometry (from 118.9+/-8.6 to 141.6+17.9 mmHg; P<0.05). Transcutaneous p(CO(2)) was initially within physiological ranges, but increased significantly after a delay during the 3rd min of cycling (from 39.7+/-3.7 to 41.1+/-4.7 mmHg; P<0.05). MFV started to rise significantly after 1 min of the exercise period (from 59.6+10.9 to 68.3+13.9 cm/s; P<0.05). PI increased immediately and significantly at the start of exercise (PI at rest 0.93+0.11; PI ergometry 1.1+0.13; P<0.05). The results were found to be reproducible in the eight volunteers. The cerebrovascular changes during ergometer exercise may reflect the combined activation of the cerebrovascular autoregulative mechanisms (neurogenic, myogenic and metabolic). The TCD-ergometer test presented here is non-invasive and would seem to present a low risk for patients who are judged fit enough for mild exercise. The test may contribute to the detection of cerebrovascular abnormalities in various diseases