Background and purpose
This study aimed to assess the prevalence of illicit drug use among epilepsy patients and its effects on the disease.
Aggression is common after traumatic brain injuries (TBI) in acute and chronic settings. However, there is limited guidance regarding its assessment and effective management. Whilst a number of pharmacological options are available for long term treatment, the evidence base is not of an adequate strength to support a unified practice. This article will explore the currently available guidelines and recommendations for treating chronic aggression after TBIs and evaluate the evidence for its pharmacological management.
Aggression is a long term neurobehavioural sequelae of TBIs with incidences quoted from 11.5-33.7%.1 In TBI patients, aggressive behaviour tends to be impulsive rather than premeditated and can manifest as episodic dyscontrol syndrome, disinhibition or exacerbated premorbid antisocial traits.2 The underlying mechanisms of aggression are complex allowing numerous and diverse interventions targeting various pathways.
In acute settings, Lombard and Zafonte (2005) describe non-pharmacological measures to manage aggression including environmental alterations and ensuring minimal or non-contact restraints. Screening for systemic causes, optimising pain control and patients’ sleep-wake cycle are also advocated. In the event of failed non-pharmacological treatment, Lombard and Zafonte (2005) recommend that medication choice should be tailored to individuals; with side effect profiles taken into consideration.3
For chronic aggression, psychological therapies are used as a first line with pharmacological interventions trialled in later stages.4 Psychological therapy options include cognitive behavioural therapy (CBT), behavioural management utilising operant learning theory and contingency management. However, a review by Alderman (2013) concluded that further evidence using scientific methods is needed to analyse these approaches.5 Comparatively, there is a diverse body of literature addressing long term pharmacological treatment although quality among studies are varied. This article will focus on the aetiology for chronic post TBI aggression, current management guidelines and the evidence for long term pharmacological interventions.[…]
Background and Purpose: The potential for adaptive plasticity in the post-stroke brain is difficult to estimate, as is the demonstration of central nervous system (CNS) target engagement of drugs that show promise in facilitating stroke recovery. We set out to determine if paired associative stimulation (PAS) can be used (a) as an assay of CNS plasticity in patients with chronic stroke, and (b) to demonstrate CNS engagement by memantine, a drug which has potential plasticity-modulating effects for use in motor recovery following stroke.
Methods: We examined the effect of PAS in fourteen participants with chronic hemiparetic stroke at five time-points in a within-subjects repeated measures design study: baseline off-drug, and following a week of orally administered memantine at doses of 5, 10, 15, and 20 mg, comprising a total of seventy sessions. Each week, MEP amplitude pre and post-PAS was assessed in the contralesional hemisphere as a marker of enhanced or diminished plasticity. Strength and dexterity were recorded each week to monitor motor-specific clinical status across the study period.
Results: We found that MEP amplitude was significantly larger after PAS in baseline sessions off-drug, and responsiveness to PAS in these sessions was associated with increased clinical severity. There was no observed increase in MEP amplitude after PAS with memantine at any dose. Motor threshold (MT), strength, and dexterity remained unchanged during the study.
Conclusion: Paired associative stimulation successfully induced corticospinal excitability enhancement in chronic stroke subjects at the group level. However, this response did not occur in all participants, and was associated with increased clinical severity. This could be an important way to stratify patients for future PAS-drug studies. PAS was suppressed by memantine at all doses, regardless of responsiveness to PAS off-drug, indicating CNS engagement.
The capacity of the brain to make structural, physiological, and genetic adaptations following stroke, otherwise known as plasticity, is likely to be critical for improving sensorimotor impairments and functional activities. Promotion of adaptive plasticity in the central nervous system (CNS) leading to sustained functional improvement is of paramount importance, given the personal suffering and cost associated with post-stroke disability (Ma et al., 2014). In addition to rehabilitation therapies to retrain degraded motor skills, animal and human studies have tried to augment recovery with neuropharmacologic interventions. Unfortunately, few if any have had a notable effect in patients or have come into routine use (Martinsson et al., 2007; Chollet et al., 2011; Cramer, 2015; Simpson et al., 2015). Methods to screen drugs based on their presumed mechanism of action on plasticity in human motor systems could speed translation to patients. However, there is currently no accepted method in stroke patients for evaluating the potential effectiveness or individual responsiveness to putative “plasticity enhancing” drugs in an efficient, low-cost, cross-sectional manner, in order to establish target engagement in humans and to avoid the extensive time and cost of protracted clinical trials.
Paired associative stimulation (PAS) is a safe, painless, and non-invasive technique known to result in short-term modulation of corticospinal excitability in the adult human motor system, lasting ∼90 min (Stefan et al., 2000; Wolters et al., 2003). Post-PAS excitability enhancement has been considered an LTP-like response thought to relate to transient changes in synaptic efficacy in the glutamatergic system at the N-methyl-D-aspartate (NMDA) receptor, since both human NMDA receptor deficiency (Volz et al., 2016) and pharmacological manipulation with dextromethorphan (Stefan et al., 2002) can block the effect. While PAS has been explored as a potential therapeutic intervention in patients with residual motor deficits after stroke (Jayaram and Stinear, 2008; Castel-Lacanal et al., 2009), it has not previously been investigated for its potential use as an assay of motor system plasticity in this context. Prior studies have suggested that motor practice and PAS share the same neuronal substrates, modulating LTP and LTD-like plasticity in the human motor system (Ziemann et al., 2004; Jung and Ziemann, 2009); therefore, as an established non-invasive human neuromodulation method (Suppa et al., 2017), we reasoned that PAS would be a suitable assay in the present study to examine the effect of a drug on motor system plasticity.
Here, we examine the effect of memantine, a drug used for treatment of Alzheimer’s disease, on the PAS response in patients with chronic stroke. Memantine is described pharmacologically as a low affinity, voltage dependent, non-competitive, NMDA antagonist (Rogawski and Wenk, 2003). At high concentrations, like other NMDA-R antagonists, it can inhibit synaptic plasticity. At lower, clinically relevant concentrations, memantine can, under some circumstances, promote synaptic plasticity by selectively inhibiting extra-synaptic glutamate receptor activity while sparing normal synaptic transmission, and hence may have clinical utility for rehabilitation (Xia et al., 2010). Interest in specifically using the drug for its interaction with stroke pathophysiology stems from animal models of both prevention (Trotman et al., 2015), in which pre-conditioning reduced infarct size, as well as for functional recovery, in which chronic oral administration starting >2 h post-stroke resulted in improved function through a non-neuroprotective mechanism (López-Valdés et al., 2014). In humans, memantine taken over multiple days has been used to demonstrate that the NMDA receptor is implicated in specific transcranial magnetic paired-pulse measures (Schwenkreis et al., 1999), and short-term training-induced motor map reorganization (Schwenkreis et al., 2005). In studies of neuromodulation, memantine blocked the facilitatory effect of intermittent theta-burst stimulation (iTBS) (Huang et al., 2007). Similarly, LTP-like plasticity induced by associative pairing of painful laser stimuli and TMS over primary motor cortex (M1) can also be blocked by memantine (Suppa et al., 2013). The effects of memantine on the PAS response have not yet been demonstrated, including examination of potential dose-response effects, which would be important for the potential clinical application of memantine for stroke recovery.
In our study, we set out to determine whether PAS might be a useful tool to probe the potential for plasticity after stroke in persons with chronic hemiparesis and apply PAS as an assay to look at drug effects on motor system plasticity using memantine. We hypothesized that (a) PAS would enhance corticospinal excitability in the contralesional hemisphere of stroke patients, and that (b) since PAS-induced plasticity is thought to involve a short-term change in glutamatergic synaptic efficacy, memantine would have a dose-dependent effect on PAS response. We predicted that at low doses, memantine would enhance PAS-induced plasticity through selective blockade of extrasynaptic NMDA receptors, whereas higher doses would inhibit PAS-induced plasticity.[…]
Neuroplasticity is a natural process occurring in the brain for entire life. Stroke is the leading cause of long term disability and huge medical and financial problem throughout the world. Research conducted over the past decade focused mainly on neuroprotection in the acute phase of stroke while very little studies targets chronic stage. Recovery after stroke depends on the ability of our brain to reestablish structural and functional organization of neurovascular networks. Combining adjuvant therapies and drugs may enhance the repair processes and restore impaired brain functions. Currently, there are some drugs and rehabilitative strategies that can facilitate brain repair and improve clinical effect even years after stroke onset. Moreover, some of compounds such as citicoline, fluoxetine, niacin, levodopa etc. are already in clinical use or are being trial in clinical issues. Many studies testing also cell therapies, in our review we will focused on studies where cells have been implemented at the early stage of stroke. Next, we discuss pharmaceutical interventions. In this section selected methods of cognitive, behavioral and physical rehabilitation as well as adjuvant interventions for neuroprotection including non invasive brain stimulation and extremely low frequency electromagnetic field. The modern rehabilitation represents new model of physical interventions with limited therapeutic window up to six months after stroke. However, last studies suggest, that time window for stroke recovery is much longer than previous thought. This review attempts to present the progress in neuroprotective strategies, both pharmacological and non-pharmacological that can stimulate the endogenous neuroplasticity in post stroke patients.
Current treatments for depression and PTSD only suppress symptoms, if they work at all. What if we could prevent these diseases from developing altogether? Neuroscientist and TED Fellow Rebecca Brachman shares the story of her team’s accidental discovery of a new class of drug that, for the first time ever, could prevent the negative effects of stress — and boost a person’s ability to recover and grow. Learn how these resilience-enhancing drugs could change the way we treat mental illness.
This talk was presented at an official TED conference, and was featured by our editors on the home page.
Background: Pharmacological management of patients with epilepsy is still a very challenging approach for the best outcome of these patients. When considering the appropriate treatment choice for patients it is necessary to take into account several factors that can influence the effectiveness and quality of life. Cancelling or changing treatment suddenly can lead to uncontrolled seizures. After a short period without seizures, many patients are tempted to abandon treatment. Cessation of treatment can be discussed after a seizure-free period for at least two years. Treatment should be discontinued gradually by reducing the dosage and constant supervision of the physician. This paper analyses briefly the general pharmacological and treatment methods in several forms of adult epilepsy.
Conclusions: Management of epilepsy means more than observing the medication prescribed by the specialist. It is also important for the patient to maintain his general health status, monitor the symptoms of epilepsy and response to treatment and take care of his safety. Involvement in the management of one’s own affection can help the patient to control his condition and to continue his routine in usual manner. The objective of antiepileptic treatment is to reduce epileptic seizures to zero without intolerable side effects. New treatments should focus not only on reducing the frequency and intensity of seizures but also improving the quality of life of patients. Key words: patient, epilepsy, therapy and dynamics.
The analysis of the specialized literature reveals that many issues regarding differential treatment of epilepsy require subsequent clarification. As far as we are concerned, we have designed and developed therapeutic recommendations, in our opinion, effective, supporting the results of treating epilepsy in its various stages, from premonition to status variants. In this context, the main element in the choice of preparations, besides the trivial clinical signs, was the use of sub-curative monitoring data, including repeated EEG examinations, which fixed the subjective response of patients. Choosing the best possible medicine or an optimal combination of medicines is sometimes difficult. The perfect antiepileptic should be long, nonsedative, well tolerated, very active in various types of convulsive and with non-harmful effects on vital organs and functions. In addition, it must be effective in various forms of active epilepsy and in treating underlying epileptic seizures and capable of restoring the electroencephalogram between seizures to its normal form [5; 9; 10; 18; 23; 24; 27; 31; 38; 40; 41; 43].
It is still debatable whether such a drug will ever be discovered, and especially one that will control all types of epilepsy. The thorough study of pharmacological properties allows us to appreciate which of the existing antiepileptics will meet the current requirements of our patients under study. Due to the fact that patients differ considerably after clinical response to known anticonvulsants and the possibilities of treatment with associated drugs are insufficiently and superficially researched, testing of more efficient substances including new combinations continues. Due to the modern medication, which benefits from a wide and sufficiently efficient range of specific drugs, a large proportion of the recurrent and the disabling sequelae of the disease can be prevented. The adverse effects of drugs are low, so many of the past patients who have been labelled for life by this suffering can now live a productive life. The actual ability to control this disease effectively prevents more of its severe consequences [12; 13; 15; 22; 29; 46; 50].
General principles of pharmacotherapy of epilepsies
In the treatment of psychiatric disorders of our patients with epilepsy we have taken into account the following principles:
Appropriate selection of the remedy, its dosing, routes of administration and possible side effects. And we took into account the following:
of the evidence of side effects of favorable and unfavorable preparations. Somatic mood dictates and the route of administration of drugs: parenteral in gastrointestinal disorders, endonasal or transorbital (by electrophoresis) when parenteral administration is not preferred.
Individual features of the patient with epilepsy (age, weight, response to anticonvulsant therapy and others) are also considered. It is often forgotten that lower doses are indicated for children and older people as the exchange of substances in them is slow and standard dose treatment leads to accumulation of preparations and adverse effects [6; 7; 14; 19].
We recommend the gradual increase of the doses, with the preference of the minimal effective doses of the drugs. All the above-described drugs are initially indicated at minimal doses, then the dose gradually increases until the first positive effects are displayed, the subsequent increase of the doses is made after a certain period of time to stabilize the positive effect.
Complex treatment – it is necessary to prescribe unimoment of anticonvulsant remedies from different classes and groups in combination with non-medication methods. Polipharmacologic treatment has certain priorities in comparison with monotherapy because it addresses different links of the pathological process. It is important to avoid the multidimensional effects of many drugs, the doubling of the mechanisms of action and the predilection of some and the same psychological processes.
Continuous therapy. The treatment of productive disorders is done until their complete jugulation (sometimes with the purpose of preventing relapse and longer), of the deficient ones by alternating the cures, with gradual modifications [28; 30; 34; 39; 42].
Principles of medication of psychosomatic syndromes in epilepsy
Criteria for the effectiveness of psychotropic remedies administered in epilepsy are those of improving the knowledge and behavioral processes. More differentiated treatment is based on syndrome of mental disorders.
a) Main mechanism of action: nootrop, general metabolism, cerebrovascular or actoprotector;
b) Predominant action on mediating processes: GABA (piracetam, fenibut, gamma-aminobutyric acid); cholin-ergic (gliatiline); dopaminergic (nakom); and combined (meclofenoxate, glycine, glutamic acid);
c) With predominant action on the function of the encephalic structures: the cerebral and subcortical (nakom), on the left hemisphere (gliatilline); on the right hemisphere (cortexil);
d) With action on psychomotor activity: major stimulation (piracetam, nakom vinpocetine), mean enhancement (aminalone, gamma-aminobutyric acid, cerebrolizine, nicergoline, tanakan), diminishment (fenibut, glycine, ci-narizine);
e) Route of administration: parenteral, internal, endo-nasal, transorbital (by electrophoresis), mixed. Duration of treatment: from 7 days to 4 months (nakom, fenibut). On the basis of this therapy it is also possible to indicate prophylactic doses of anticonvulsants.
Emotional productive disruptions. In the states of excitation are indicated predominantly sedative neuroleptics and tranquilizers, antidepressants – in depression, tranquilizers and antiepileptics – in dysphoria, in anxiety states -neuroleptics and tranquilizers.
Productive districts nearby. Psychoparticular depressions are typically treated with “inor” euroleptics, preferably “behavioral correctors” or low doses of risperidone and tranquilizers; in neurotic manifestations (asthenia, obsessions, hysteria, hypocondria) are used tranquilizers and low doses of antidepressants [1; 2; 3; 4; 8; 11; 25; 26].
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My 54-year-old husband sustained a TBI when he fell asleep at the wheel while driving and hit a tree. The doctors say that he damaged all four parts of his brain. It’s been more than one and a half years and he’s still totally dependent on me to take care of him. Do you think Ritalin would help stimulate his brain?
Methylphenidate (Ritalin) is one of the commonly used brain stimulants in people who have suffered traumatic brain injury. It increases chemicals in the brain that have a stimulating effect (norepinephrine and dopamine).
After traumatic brain injury, doctors commonly prescribe Ritalin for low arousal or initiation, poor attention and concentration, depression, and slow processing speed. There is research that shows that Ritalin may speed recovery early after moderate to severe TBI. There is also research showing that Ritalin increases mental processing speed after TBI, which can improve memory function in some people.
All medications have side effects and the risks need to be weighed against possible benefits. One of the good things about the standard formulation of Ritalin is that it is short acting so if side effects occur they wear off in a few hours. Some potential side effects include keeping you up at night (if taken too close to bedtime), decreased appetite, headache, irritability, and paranoia.
In your husband’s case, his doctor needs to look at why he is so dependent. If arousal, attention, and/or initiation are playing a significant role, a stimulant can be considered. Careful monitoring for effects and/or side effects is needed when starting this medication and it should only be done by a doctor who has experience in caring for people with traumatic brain injury. Ritalin and most stimulants are controlled substances and will require frequent visits to the doctor for prescriptions.
To examine the effectiveness of levetiracetam and phenytoin for seizure prophylaxis following brain injury.
This study aimed to assess the prevalence of illicit drug use among epilepsy patients and its effects on the disease.
We systematically interviewed epilepsy outpatients at a tertiary epilepsy clinic. Predictors for active cannabis use were analysed with a logistic regression model.
Overall, 310 subjects were enrolled; 63 (20.3%) reported consuming cannabis after epilepsy was diagnosed, and 16 (5.2%) used other illicit drugs. Active cannabis use was predicted by sex (male) [odds ratio (OR) 5.342, 95% confidence interval (95% CI) 1.416–20.153] and age (OR 0.956, 95% CI 0.919–0.994). Cannabis consumption mostly did not affect epilepsy (84.1%). Seizure worsening was observed with frequent illicit (non-cannabis) drug use in 80% of cases.
Cannabis use does not seem to affect epilepsy; however, frequent use of other drugs increases seizure risk.