It is used to test whether a set of synaptic connections of these cells exists, which, paced by the same rhythmical thalamic input, could produce spindles under normal conditions and spike and wave discharges SW under conditions of cortical hyperexcitability. This is possible if the interneurons do not provide recurrent excitatory or inhibitory input on themselves, if the thalamic afferents contact the cortical projecting pyramidal cells through local excitatory neurons, and if the inhibitory interneurons receive input only from the pyramidal cells. The results suggest that an increase of all cortical synaptic actions both excitatory and inhibitory is sufficient for the transition from spindles to the first stages in the development of SW discharges in the cortex, whereas the thalamus can be driven to the SW characteristic frequency at the immediate next stages.
Unable to display preview. Download preview PDF. Skip to main content. Advertisement Hide. Simulation study for the transition from spindles to spike and wave epileptogenesis. Authors Authors and affiliations G.
Antoniadis G. This is a preview of subscription content, log in to check access. Avoli, M. Connors, B. Toilet habits. This in itself can lead to constipation. Additionally, try and give yourself enough privacy and time to poop comfortably, where possible. Toilet position also matters — some find a footstool helps them to get into a better position with knees raised higher than ankles. As always, exercise has so many benefits and can really help to keep things moving.
Aim to do at least minutes of physical activity a week. Exercise will also help improve you mood, energy levels and general fitness. You may well be experiencing lethargy due to your medication or seizures, therefore it is a good idea to gradually increase exercise into your schedule. As little as 10mins has been shown to have health benefits and you do not need an expensive gym membership in order to achieve this.
For example, you can do things in the house, dance to some music whilst cleaning, or look on YouTube for some exercise videos I mean; what can't you find on the internet these days?! Also, getting out into the fresh air can also help, e.
Therefore, stress levels should not be forgotten when considering any issues we may have with our bowels although most people experience looser motions rather than constipation. Try and manage your stress levels through yoga, meditation, or exercise to help with this. In fact, we are also now discovering how much our gut affects how we feel rather than our brain dictating our emotions.
So, start to make these changes to your diet and lifestyle and you should see an improvement. However, it is important to remember that if you ever experience any changes in your bowels more mucus, change in stool consistency etc. With some simple, long-term observations and changes in diet and lifestyle, we can help to unclog the poop chute - epilepsy or no epilepsy!
Georgina Goss. Tack, J. Muller-Lissner, S. Diagnosis and treatment of chronic constipation - a European perspective. Neurogastroenterology and Motility.
chapter and author info
Suares, N. Considering these specific study features in the design, we do not only follow international high quality standards for clinical research, but also address potential biasing effects in clinical veterinary trials [ 81 , 82 ]. We are confident that this design significantly increases the accuracy and representative nature of our expected findings on the use of MCT oil as nutritional add-on management in dogs with IE. Regression-to-the mean arises often in clinical trials when a variable is extreme on its first, but closer to the mean on its second measurement or vice versa [ 84 , 85 , 86 , 87 ].
In canine epilepsy trials, usually an extreme hardest-to-treat group is selected from an epileptic dog population based on the measurement of a particular variable.
Dietary Neurotransmitters: A Narrative Review on Current Knowledge
If this effect is not considered, the clinical trial or the interpretation of our obtained data can lead to incorrect conclusions, so must be then expected to be inaccurate or incorrect [ 88 ]. The placebo effect is a well-known phenomenon in human medicine [ 89 ], however, limited information about the placebo effect exists in veterinary medicine to date [ 90 ]. Reports so far described caregiver placebo effect especially in association to chronic anti-inflammatory or analgesic treatment in small animals [ 91 , 92 , 93 ].
The occurrence of placebo effects are significantly associated with response expectancy [ 89 ]. In canine epilepsy trials, the expectation from owners is usually higher due to physiological stress, often poor seizure control and the continuous negative impact on their own QoL [ 70 , 79 , 94 , 95 ] so that a notably subjective influence on the dog can be more likely.
A general run-in period given by the recruitment process, where owners are first enrolled on a waiting list and their dog are checked on study criteria before giving the first treatment, will also support to mitigate the response expectancy. Another impact can derive from the Hawthorne effect or also known as the observer effect. When study individuals are aware of being observed within a clinically trial, their response to the trial situation can not only modify, often falsify study variables.
The Hawthorne effect can therefore also be seen as an pre-placebo expectation [ 96 ]. Alike in epilepsy research in human medicine [ 97 ], such type of reactivity should be considered as influencing factors from owners and their dogs in the design of canine epilepsy trials. The integration of a dietary crossover in the mid of observation time, allows each participant to receive both dietary interventions.
Each study object will therefore serve as its own control and reduce significant biasing effects [ 98 ]. Even though the retrospective baseline is documented, the data will be completely disregarded in most of the analysis and only applied were appropriate. This exclusion is to minimise the regression-to-the-mean and observed placebo effect in other canine epilepsy trial in veterinary medicine [ 83 ].
Not only observer, but also investigator bias might otherwise provoke incorrect observations, so that using a double-blinded design is most appropriate here. Describing the blinding methodology is important to give veterinarians the ability to assess the validity of the test results and apply in clinical environment [ 99 ].
A core principal for clinical trials in human and veterinary medicine is the randomisation [ , ]. The process of randomised allocation of each dog on its day of enrolment is considered in this study as being essential. The random assignment of each study subject to a predefined block 1st DS AB , 2nd DS BA reduces the impact of selection bias and increases the validity of the expected study results. Furthermore, the detailed reports about the allocation process makes it possible for practitioners to critically review the impact of bias on study results and make informed decisions regarding the treatment of their own epileptic patients [ ].
Acting against hypothetical, multi-sided bias by implementing described trial features, should enable us to collect and assume not only controlled, but also representative data about MCT consumption in dogs diagnosed with IE. Dropout is often used as an outcome measure in clinical trials.
But, in randomised clinical trial with epileptic patients, it appears to be higher than other clinical studies and partly explained by trial design features thus providing direction for future trial designs [ ]. Furthermore, in another study on ketogenic diet, twenty-two dogs in each group were suggested to be sufficient for showing significant differences between two diet groups for seizure frequency [ 51 ].
Although study features will be implemented to prevent massive biasing effects, limitations are in any clinical trial and must be reflected critically on data analysis. One limitation of this study design is that an intention to treat analysis ITTA can be challenging or impossible to perform. ITTA is an approach to the analysis in which our recruited patients are evaluated as block randomised, regardless of the dietary intervention they actually received [ ]. This is especially hard to realise when most or all dogs that dropout are within the first study period, as was the case in our former MCT study [ 24 ].
There is a chance that if randomisation is not carried out carefully, that results could be skewed as study dropouts will not be included in the paired statistical analysis. It is therefore of pivotal importance to document in detail and if possible, compare statistically the reasons why owners withdraw their dog from the study and during which study period. As aforementioned in the last study [ 24 ], the majority of the dropout dogs 7 out of 10 did not complete the first respective randomised allocated diet, hence there was no outcome measure at all for the remaining respective diet group.
Using the last observation carried forward is not possible as there was no observation for the second diet. Furthermore, utilising a statistical imputation method of the outcome measure would require profound assumptions to be made on the missing outcome.
Statistical imputation of outcome assuming the MCT and placebo diet would be the same introduces bias towards the null.
- Neurotransmitters as food supplements: the effects of GABA on brain and behavior.
- Photomask Fabrication Technology (Professional Engineering).
- 1st Edition;
- Prospectus for the Public Offering of Securities in Europe: Volume 1: European and National Legislation in the Member States of the European Economic Area (Law Practitioner Series).
- Your Dream Wedding on a Budget.
- From Field to Fork: Food Ethics for Everyone?
On the other hand, imputation assuming a difference on the probability of the outcome introduces bias towards the treatment effect. Considering that the primary aim of the study was to determine the anti-seizure efficacy of the ketogenic MCT diet, the utilising of a per protocol analysis method is more suitable and logical [ 82 ]. Oil supplementation for dog owners as additional treatment for general health or targeted to epilepsy management is a common practice [ ]. As the clinical trial aims to prove ketogenic MCT oil supplementation as nutritional management for epileptic dogs, dietary characteristics and acceptance must be considered.
As a variable, palatability is the measure of intake of a food that indicates acceptance, or the measure of preference of one food over another [ 55 ]. Food with different characteristics can alter voluntary food intake by affecting palatability, taste or flavour [ 56 ]. Excluding bias linked to palatability in the main clinical trial, the food intake ratio should be similar.
The mean food intake, as a percentage, can be calculated for each period and was used to assess the dogs eating preference. An intake ratio IR of over 0. If intake ratio IR for a feeding period was greater than 0. Both oils will be proven in advance in a small palatability study to be well tolerated, similar consumed and no food preference was observed.
In summary, a good and similar palatability without any acute gastrointestinal side effects should be concluded and monitored in the prospective dietary trial. Canine nutrition needs to be considered for epilepsy management [ 60 , , , , ]. Diet composition, content and some of the DSs mentioned could influence pharmacokinetic properties of ASDs and potentially modulate their efficacy [ 39 , 61 ].
Owners of dogs with more severe epilepsy phenotypes, as recruited for this study, are likely to change unconsciously dietary regimes or DS due to higher levels of psychological stress [ 70 , 79 , ], therefore owners were asked to keep diets and DS constant throughout the trial.
In addition, owners were asked to daily monitor any changes in seizures, drugs used, and potential adverse events seen. Nevertheless, a balanced supply of all nutrients is routinely not checked in first opinion practice and might play a role for the interpretation of dietary effects occurring from MCT oil supplementation.
We will take great care of assessing the baseline diet as aforementioned.