Pathology of Dizziness of Central Origin

Comparison of imipramine-imipraminium in mice: To elucidate central or peripheral origin of effects of imipramine

The vagus nerve exerts a profound influence on the heart, regulating the heart rate and rhythm. An extensive vagal innervation of the cardiac ventricles and the central origin and extent of this innervation was demonstrated by transynaptic transport of pseudorabies virus with a virulent and two attenuated pseudorabies viral strains. The neurons that innervate the ventricles are numerous, and their distribution within the nucleus ambiguus and dorsal motor nucleus of the vagus is similar to that of neurons innervating other cardiac targets, such as the sino-atrial node. These data provide a neuroanatomical correlate to the physiological influence of the vagus nerve on ventricular function.

In the midcollicular decerebrate cat we have observed unique respiratory variation in heart rate (respiratory-heart rate relationship, RHRR) in respiratory intervals of 2-7 s or Biot's breathing of paired breaths at 16-s intervals. Cardiac slowing that marked the respiratory segmentation of the heartbeat showed consistent relationship with the breath it preceded by 1 to 5 s. Thus, association of respiration and heartbeat must include synergistically central interrelated origins for respiration cardiac rates constituting the RHRR.

In primary hypertension a mild hyperresponsiveness of hypothalamic, sympatho-hormonal centres to psychosocial stimuli forms a major pathogenetic element, although high salt intake in some subjects may contribute via volume expansion. Hypertension is often associated with another ?civilisation? disorder, the metabolic syndrome, defined as abdominal obesity, insulin resistance and dyslipidaemia. According to recent research, the metabolic syndrome has in all likelihood a central neuroendocrine origin in the form of enhanced engagement of the hypothalamic-pituitary-adrenal (HPA) axis. Here the peripheral endocrine perturbations act as triggers for both central obesity and the metabolic abnormalities. The reaction pattern characterising early primary hypertension is identical with, or closely related to, the ?defence reaction?, while that leading to the metabolic syndrome is similar to that of the ?defeat reaction?. Both belong to the primitive survival reactions, common to all mammals, though man can control, or at least mask, his outward-behavioural part but not the neuro-hormonal expressions. Animal experiments show how frequent or chronic mental challenges are capable of engaging these limbic-hypothalamic centres, affecting blood pressure regulation as well as endocrine-metabolic regulation. Furthermore, these centres are tightly coupled functionally, and their signals to the periphery often combined. On a long-term basis their engagements appear to be decisive for the development of both primary hypertension and the metabolic syndrome, as suggested by intervention studies. In both these ?disorders of civilisation?, observations strongly indicate that psychosocial stress, socioeconomic handicaps, lack of exercise, abuse and also psychiatric traits are involved. Such factors, characteristic of current competitive society, probably cause mixed engagements of the two above-mentioned neuro-hormonal patterns, and thereby, with time, primary hypertension and the metabolic syndrome, with end-points such as coronary artery disease, diabetes mellitus type2 and stroke. Susceptibilty to such developments is probably enhanced by genetic factors. This overview of recent developments therefore serves to emphasise how both primary hypertension and the metabolic syndrome seem to have a common central origin. Central regulatory factors are often overlooked, partly because it is not realised that limbic-hypothalamic centres are the major regulators of both circulatory and metabolic events, and partly because of the long period of time required before these disease end-points are reached.

Stimulus-independent spike-rate variability tends to be weakly correlated between neuronal pairs throughout sensory cortex. It is frequently suggested that these “noise” correlations ( r sc ) reflect the stochastic nature of sensory input pathways, from which it follows they place hard limits on the fidelity of sensory encoding. For an optimal linear decoder, correlations limit information when they follow a particular relationship with neuronal preferences (so-called “differential” correlation structure). However, r sc may also reflect shared input from signals that are centrally generated and potentially under voluntary control. If so, its impact on sensory encoding is unclear. We sought to directly test whether the structure of noise correlations in visual cortex reflects signals of central origin during perceptual decision making, by measuring r sc in contexts where task instruction changed but retinal input was fixed. We recorded population spiking activity in primary visual cortex (V1) of rhesus monkeys, while the subjects performed a coarse orientation discrimination task using filtered noise. The discriminanda were fixed in a given recording session but were varied between sessions. We found that r sc structure changed with the task even on zero-signal trials which were identical for all sets of discriminanda, indicating a central origin. Specifically, pairs of neurons which preferred the same orientation discriminandum were more highly correlated than pairs preferring opposite discriminanda, while pairs not well tuned for the task showed no modulation. At first sight, these changes appear to have a detrimental impact on the information capacity of the population, since they are nearly “differential” in structure. However, if downstream areas can distinguish inputs of central and peripheral origin, then the observed r sc structure no longer constrains the information limit. More complex models of the relationship between feedforward and feedback pathways in sensory processing are needed to determine when noise correlations between sensory neurons are truly information-limiting.

In rats exposed to restraint and water immersion stress, inhibitory effects of atropine (ATR) and chlorpromazine (CPZ) on stress-induced gastric ulceration and motility were studied to clarify which of central and peripheral origins was responsible for these effects. The drug dose ratio of peripheral (intravenous, i.v.) route versus central (intracerebroventricular, i.c.v.) route required to produce an approx. 50% inhibition of gastric ulceration or motility was estimated. Gastric ulceration was prevented by pretreatment with each drug via either route, and there was no great difference in the dose ratio of each drug (i.v.:i.c.v. = 4:1) for the inhibition. The stress-enhanced gastric motility was immediately depressed by each drug via either route. This inhibitory effect of CPZ was short-lasting as compared with that of ATR, and the complete blockade was observed after administration of i.v. ATR or i.c.v. CPZ at higher doses. The ATR dose ratio for this inhibition was less than 10, while the CPZ dose ratio was from 10 to 25. The treatment with CPZ, but not with ATR, caused a definite change in EEG patterns, along with a decrease in body temperature or heart rate. The effect of pretreatment with ATR or CPZ on gastric motility during stress was also investigated. Only the administration of ATR, via either route, appreciably inhibited the gastric motility. Thus, it was suggested that: (1) the inhibitory effect of ATR on gastric motility may be of peripheral rather than central origin, while that of CPZ predominantly of central origin; (2) the anti-ulcerogenic effect of ATR and CPZ may be predominantly of peripheral origin, and the mechanisms involved in ATR may be associated with inhibition of gastric motility, which is different from those in CPZ.

<p class="abstract"><strong>Background:</strong> Vertigo, by definition, is a subjective sense of imbalance, and can result from a variety of disorders both peripheral and central. Although perfect function is required for precise balance and eye movement control, man is able to function adequately with only two of the three main sensory inputs. Great difficulty, however, occurs if only one system is intact, or if the control integrating mechanisms within the nervous system are deranged. Minor deficiencies of any, or all three sensory inputs may give rise to symptoms of imbalance. The disorders causing vertigo may be of peripheral or central origin, and accurate diagnosis of the underlying pathology is warranted for effective treatment.</p><p class="abstract"><strong>Methods:</strong> The study was carried out in the Department of Otorhinolaryngology, Regional Institute of Medical Sciences, Imphal. 50 cases presenting with symptoms of vertigo were studied irrespective of age, sex, caste, religion, socio-economic status and duration of illness. They were subjected to a thorough clinical examination and relevant investigations with main emphasis on vestibular tests and electronystagmography in every patient.</p><p class="abstract"><strong>Results:</strong> Vertigo of peripheral and central lesions accounted for 64% and 12% respectively. Idiopathic vertigo in which no neurotological abnormality is detected accounted for 24% of cases. Meniere’s disease (28%) comprised the single largest group amongst the peripheral vertigo. Majority of the patients (58%) presented with hearing impairment as associated symptom.</p><p class="abstract"><strong>Conclusions:</strong> Ninety percent of patients presented with less than one year duration of vertigo. Vertigo caused by peripheral vestibular lesion presents as acute, unprecipitated, short-lived episodes associated with nausea and vomiting, while vertigo of central vestibular origin follows a more gradual and insidious onset of continual imbalance.</p>

Recent work by our group showed that cold-induced vasodilation (CIVD) is a centrally originating phenomenon caused by sympathetic vasoconstrictor withdrawal; it is dependent on excess heat, and it may be triggered by excess heat with the purpose of preserving thermal balance (Flouris et al. 2008; Flouris and Cheung 2009a, b). To this effect, Daanen and Layden (2009) recently argued that, instead, our data show that CIVD is of peripheral origin. Thus, our aim in this letter is to briefly clarify misconceptions that may have led Daanen and Layden to questionable inferences. We have reported a sympathetic withdrawal during CIVD (Flouris and Cheung 2009b) in line with the evidence that CIVD is attributed to an interruption of adrenergic neurotransmission (Johnson et al. 1986). Given that sympathetic activity is generally inversely associated with core temperature (Sawasaki et al. 2001), Daanen and Layden derived that ‘‘...the sympathetic activity must have been continuously increasing during the cooling period’’ which led them to the conclusion that CIVD in our study ‘‘...was of peripheral rather than central origin’’. Since our experiment demonstrated a sympathetic withdrawal—not activation—during CIVD, the logic and conclusion of Daanen and Layden are fallacious. In their letter, Daanen and Layden argue that careful reading of the literature does not support our claim that CIVD can be induced by whole body cold exposure. Indeed, Montgomery and Williams (1977) did not investigate CIVD and we were misled by their reference to ‘‘cold vasodilation’’ in their discussion. However, the remaining claims of Daanen and Layden are inaccurate as Berry et al. studied CIVD [‘‘...the occurrence of cold-induced vasodilation (CIVD) found in the present study agrees with that observed by...’’ (1984)], while Steegmann [‘‘...90 min of exposure to 1 C air moving over the face and body at about 6 m/min’’ (1979)] as well as Brajkovic and Ducharme [‘‘...subjects walked comfortably (4.8 km/h) on a treadmill during exposure to four 90-min tests, each at a different environmental condition...’’ (2006)] did, in fact, expose the entire body to cold, not just the face. Moreover, Shitzer’s group did induce CIVD via whole body cold exposure in the papers that we referenced (Shitzer 1998; Shitzer et al. 1991, 1998a, b). There is, obviously, a mistake here as Daanen and Layden refer to papers by Shitzer’s group (Shitzer et al. 1996, 1997) that we never referenced. A final point of Daanen and Layden was that the phenomenon we interpreted as CIVD in our original experiment (Flouris et al. 2008) was a normal heat loss mechanism because, at times, finger temperature was up to 33.5 C. However, finger temperature for a large part of the experiment was below 15 C and was very often as low as 5 C, confirming that the cold stimulus to the hands was strong enough to evoke CIVD. Also, similar insulation of the body and hands has been used in several studies in the past (Santee et al. 1990; Shitzer 1998; Shitzer et al. 1991, 1998a, b), all of which incorporated shorter and less severe exposures compared to ours but reported a large number of CIVDs. In conclusion, no salient data or arguments have thus far been presented refuting that CIVD is a centrally originating Communicated by Susan Ward.

Features of Microparticle-Associated Procoagulant Activity in Patients with Thrombocytopenias of Immune and Central Origin

Plasma fibrinogen in the diagnosis of neurogenic hyperthermia

Key pointsCardiac vagal tone is a strong predictor of health, although its central origins are unknown.Respiratory‐linked fluctuations in cardiac vagal tone give rise to respiratory sinus arryhthmia (RSA), with maximum tone in the post‐inspiratory phase of respiration.In the present study, we investigated whether respiratory modulation of cardiac vagal tone is intrinsically linked to post‐inspiratory respiratory control using the unanaesthetized working heart‐brainstem preparation of the rat.Abolition of post‐inspiration, achieved by inhibition of the pontine Kolliker‐Fuse nucleus, removed post‐inspiratory peaks in efferent cardiac vagal activity and suppressed RSA, whereas substantial cardiac vagal tone persisted. After transection of the caudal pons, part of the remaining tone was removed by inhibition of nucleus of the solitary tract.We conclude that cardiac vagal tone depends upon at least 3 sites of the pontomedullary brainstem and that a significant proportion arises independently of RSA.Cardiac vagal tone is a strong predictor of health, although its central origins are unknown. The rat working heart‐brainstem preparation shows strong cardiac vagal tone and pronounced respiratory sinus arrhythmia. In this preparation, recordings from the cut left cardiac vagal branch showed efferent activity that peaked in post‐inspiration, ∼0.5 s before the cyclic minimum in heart rate (HR). We hypothesized that respiratory modulation of cardiac vagal tone and HR is intrinsically linked to the generation of post‐inspiration. Neurons in the pontine Kölliker‐Fuse nucleus (KF) were inhibited with bilateral microinjections of isoguvacine (50–70 nl, 10 mm) to remove the post‐inspiratory phase of respiration. This also abolished the post‐inspiratory peak of cardiac vagal discharge (and cyclical HR modulation), although a substantial level of activity remained. In separate preparations with intact cardiac vagal branches but sympathetically denervated by thoracic spinal pithing, cardiac chronotropic vagal tone was quantified by HR compared to its final level after systemic atropine (0.5 μm). Bilateral KF inhibition removed 88% of the cyclical fluctuation in HR but, on average, only 52% of the chronotropic vagal tone. Substantial chronotropic vagal tone also remained after transection of the brainstem through the caudal pons. Subsequent bilateral isoguvacine injections into the nucleus of the solitary tract further reduced vagal tone: remaining sources were untraced. We conclude that cardiac vagal tone depends on neurons in at least three sites of the pontomedullary brainstem, and much of it arises independently of respiratory sinus arrhythmia.

Sunburn—A human inflammatory pain model for primary and secondary hyperalgesia

Head-positioning maneuvers can lead to paroxysmal nystagmus and vertigo, which are usually due to a peripheral vestibular disorder like, for example, benign paroxysmal positioning vertigo (BPPV). They are less commonly caused by a central lesion (central paroxysmal positioning nystagmus, cPPV). While many typical features do not permit differentiation between BPPV and cPPV, for example, latency, course, and duration of nystagmus and vertigo during an attack, the direction of nystagmus often does. The nystagmus in BPPV always beats in the direction aligned to the affected semicircular canal plane, i.e., horizontal for the horizontal canal and vertical-torsional for the vertical canals. Any other direction (paroxysmal torsional, upbeat, or downbeat nystagmus) indicates a central origin. Three cases of cPPV exhibiting nystagmus in the latter directions are presented. In one of the cases with paroxysmal downbeat nystagmus and vertigo, all other parts of the neurological examination and brain imaging initially showed no lesion in the posterior fossa. The direction of nystagmus was the only sign that indicated a central origin.

Objectives: We investigated whether the proportion of intracerebral haemorrhage (ICH) due to cerebral amyloid angiopathy (CAA) differs between patients of Eastern and Western origin. Methods: This is a retrospective international cross-sectional study of consecutive first-ever spontaneous ICH patients (including patients with surgical intervention) admitted to one stroke centre in the United Kingdom (Western centre origin) and one in Japan (Eastern centre origin) during the same period. We classified spontaneous ICH into “CAA-related ICH” defined by the Edinburgh CT diagnostic criteria, and “other ICH”. We used multivariable logistic regression analyses to assess the relationship between CAA-ICH and geographical location (Western or Eastern centre origin) or ethnicity (Western [reference], East Asian, or other) with adjustment for confounders. Results: Of 334 patients (median age, 71 years; male, 54%; Western centre origin, 58%), 15% were classified as CAA-ICH, and 85% were defined as other ICH. In multivariable logistic regression analysis, Eastern centre and ethnicity had a lower proportion of CAA-ICH (odds ratio [OR] vs Western centre origin 0.47, 95%CI 0.23-0.98; OR [vs. white] 0.41, 95%CI 0.20-0.97, respectively).The estimated incidence of CAA-related ICH in East Asian was similar to that in White populations, but the rate of other ICH was 2.5-fold higher in East Asian populations. Sensitivity analyses using the modified Boston criteria for diagnosis of CAA-related ICH showed similar results. Conclusions: The proportion CAA-ICH is lower in an Eastern compared to a Western population; this appears to be explained by a higher incidence of ICH due to hypertensive (deep perforator) arteriopathy in East Asian populations.

Hypotensions d’origine endocrinienne