Disease episodes

Iloprost is mainly used in patients with chronic critical leg ischemia due to atherosclerosis or Buerger s disease. Episodic digital ischemia in patients with systemic sclerosis or related disorders is another use. The most frequently observed adverse effects, facial flushing and headache, are caused by profound vasodilatation. 

Mental Disease Episodes Neural Impulse Pattern... 

Most theories about the origin of mood disorders refer to the subcellular or molecular level, mainly emphasizing an imbalance between different transmitter systems [17] as a possible cause for unipolar depression as well as bipolar disorders. No concrete concepts exist to explain how and in which way such molecular disturbances modify the neural dynamics and lead to an increased mental vulnerability with progressive occurrence of disease episodes. 

Additional information about the underlying dynamics comes from clinical observations which indicate that the occurrence of disease episodes in the course of disease progression follows general rules. Despite a large variability of individual time courses, there are typical patterns of disease episodes at different disease states (Fig. 7.2a). In the course of disease progression the patterns change from iso-... 

Fig. 7.2 (a) The prototypical time course of disease episodes in affective disorders (modified after [18]). Disease episodes are initially related to external stressors with increasing strength of the episodes (kindling) which then leads to autonomous progression (episode sensitization) with periodically occurring disease episode of increasing frequency up to ultra-rapid, chaotic mood fluctuations, (b) Analogous activity pattern of... 

The indications which justify such an approach are directly provided by the episode patterns. As described above, in specific parts of disease progression the disease episodes occur periodically, while they develop rather randomly before, with no exact bifurcation point in between. Accordingly, we do not expect the mechanism of episode generation to change completely when it goes from random to periodic disease episodes. We assume that this reflects disease-related alteration of the system dynamics and we expect that this also holds true for the transitions to chaotic disease patterns. 

To simulate the disease episodes and subthreshold oscillations we again refer to our neuronal modeling approaches (Fig. 7.2b). The algorithms have been implemented with a simple but physiologically plausible approach, i.e. with two nonlinear feedback loops, one positive and one negative. Depending on the parameter setting, such a system can attain stable dynamics but also can develop oscillations. 

Fig. 7.3 Deterministic (a) and noisy (b) computer simulations of the time course of affective disorders showing the intervals between successive disease episodes (interval duration) as a function of a disease variable S and examples of episode generation from different disease states (figure modified after [2]). In deterministic simulations (a), there is a progression from steady state (S = 18) to subthreshold oscillations (S = 22) with immediate onset of periodic event generation at a certain value of S (slightly below S = 60). With further increase of S, the intervals between successive episodes are continuously...

While the above simulations describe how the disease pattern vary as a function of the disease state, the following simulations show that our model can also account for kindling phenomena and autonomous progression. This needs some model extensions which were made in reference to the above-mentioned assumption of episode sensitization which are assumed to be due to residues (memory traces) of previous disease episodes. For simplicity, and because the real mechanisms are unknown, we introduced an additional, positive feedback loop which is implemented exactly in the same way as the other feedback variables [4—7, 25]. The model now also includes a dynamic disease variable Sp (Fig. 7.4a). The specialities are that it only activates when a disease episode occurs (episode sensitization) and that it has long relaxation times (memory trace). 

It depends on the parameter adjustments, i.e. on the actual vulnerability, whether the system runs into autonomous progression. This will never happen in a healthy steady state. Even a strong external stimulus can induce only one and only a transient depressive episode. The situation drastically changes when the system is tuned to a vulnerable state. Also, when the original dynamics are still in a steady state, the initiation of one disease episode can be sufficient to induce successive episodes with autonomous progression (Fig. 7.4b). 

There are the very variable rhythms in the occurrence of disease episodes with considerable changes of disease intervals during the course of disease progression from years to months to weeks and even to days and hours. Such global behavioral rhythms are manifestations of the mental disease while the mood of mentally stable, healthy persons rather randomly fluctuates mainly following the environmental influences with mostly stochastic up and downs. 

AM Gayoso, N Ciocco. Observations on Prorocentrum lima from North-Patagonian coastal waters (Argentina) associated with a human diarrhoeic disease episode. Harmful Algae News 22 4, 2001. 

In the case of chronic liver disease, episodic HE and persistent HE were defined and the term minimal hepatic encephalopathy (MHE) was coined to replace the hitherto inappropriate term subclinical encephalopathy . It is expected that this new system of classification will help to dispel the confusion frequently present in current textbook definitions and to facilitate multi-centre clinical trials in HE. 

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