The (in)Significance of the Addiction Debate

The (in)Significance of the Addiction Debate, Abstract Substance addiction affects millions of individuals worldwide and yet there is no consensus regarding its conceptualisation. Recent neuroscientific developments fuel the view that addiction can be classified as a brain disease, whereas a different body of scholars disagrees by claiming that addictive behaviour is a choice.,

Abstract


Substance addiction affects millions of individuals worldwide and yet there is no consensus regarding its conceptualisation. Recent neuroscientific developments fuel the view that addiction can be classified as a brain disease, whereas a different body of scholars disagrees by claiming that addictive behaviour is a choice. These two models, the Brain Disease Model and the Choice Model, seem to oppose each other directly. This article contends the belief that the two models in the addiction debate are polar opposites. It shows that it is not the large amount of addiction research in itself what sets the models apart, but rather their extrapolated conclusions. Moreover, some of the most fiercely debated aspects - for instance, whether or not addiction should be classified as a disease or disorder - are irrelevant for the conceptualisation of addiction. Instead, the real disagreement is shown to revolve around capacities. Discussing addiction-related capacities, especially regarding impaired control, rather than the assumed juxtaposition of the two models can be considered the true addiction debate. More insight into the extent to which the capacities of the addicted individual were affected would be highly useful in various other areas, especially legal responsibility.

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Disorders of the spinal cord and roots

Disorders of the spinal cord and roots, I, Introduction

The distinctive patterns of myelopathy (disorder of the spinal cord) and radiculopathy (disorder of spinal roots) are a direct consequence of the striking anatomy of the spinal cord:

  • its near cylindrical, segmental structure of great length (42–45 cm in adults)

  • the marked proximity of ascending and descending long tracts within the confines of a narrow cross sectional area (the maximum circumference of the cervical enlargement of the cord is approximately 38 mm)

  • enclosure by meninges and vertebral column

  • vulnerable blood supply.

  • Having established that a patient's clinical presentation localises to the spinal cord and/or roots, clues to the pathological diagnosis emerge from the timing of the symptoms (table 1), as is usually the case in neurology.

    Neuroanatomy and specific syndromesSpinal cord

    The relationships of the white matter tracts to one another and to the..., admin,

    Regulation of microglial TMEM119 and P2RY12 immunoreactivity in multiple sclerosis white and grey matter...

    Regulation of microglial TMEM119 and P2RY12 immunoreactivity in multiple sclerosis white and grey matter..., Multiple Sclerosis (MS) is the most common cause of acquired neurological disability in young adults, pathologically characterized by leukocyte infiltration of the central nervous system, demyelination of the ..., Multiple Sclerosis (MS) is the most common cause of acquired neurological disability in young adults, pathologically characterized by leukocyte infiltration of the central nervous system, demyelination of the ..., admin,

    Molecular signature of different lesion types in the brain white matter of patients with progressive multiple...

    Molecular signature of different lesion types in the brain white matter of patients with progressive multiple..., To identify pathogenetic markers and potential drivers of different lesion types in the white matter (WM) of patients with progressive multiple sclerosis (PMS), we sequenced RNA from 73 different WM areas. Com..., To identify pathogenetic markers and potential drivers of different lesion types in the white matter (WM) of patients with progressive multiple sclerosis (PMS), we sequenced RNA from 73 different WM areas. Com..., admin,

    Aldehyde dehydrogenase 2 activity and aldehydic load contribute to neuroinflammation and Alzheimer’s...

    Aldehyde dehydrogenase 2 activity and aldehydic load contribute to neuroinflammation and Alzheimer’s..., Aldehyde dehydrogenase 2 deficiency (ALDH2*2) causes facial flushing in response to alcohol consumption in approximately 560 million East Asians. Recent meta-analysis demonstrated the potential link between AL..., Aldehyde dehydrogenase 2 deficiency (ALDH2*2) causes facial flushing in response to alcohol consumption in approximately 560 million East Asians. Recent meta-analysis demonstrated the potential link between AL..., admin,

    Disorders of the spinal cord and roots

    Disorders of the spinal cord and roots, I, Introduction

    The distinctive patterns of myelopathy (disorder of the spinal cord) and radiculopathy (disorder of spinal roots) are a direct consequence of the striking anatomy of the spinal cord:

  • its near cylindrical, segmental structure of great length (42–45 cm in adults)

  • the marked proximity of ascending and descending long tracts within the confines of a narrow cross sectional area (the maximum circumference of the cervical enlargement of the cord is approximately 38 mm)

  • enclosure by meninges and vertebral column

  • vulnerable blood supply.

  • Having established that a patient's clinical presentation localises to the spinal cord and/or roots, clues to the pathological diagnosis emerge from the timing of the symptoms (table 1), as is usually the case in neurology.

    Neuroanatomy and specific syndromesSpinal cord

    The relationships of the white matter tracts to one another and to the..., admin,

    Doing without valproate in women of childbearing potential with idiopathic generalized epilepsy: Implications...

    Doing without valproate in women of childbearing potential with idiopathic generalized epilepsy: Implications..., Abstract Objective Valproate (VPA) use in women with idiopathic generalized epilepsy (IGE) who are of reproductive age has been a matter of concern and debate, which eventually led to the recent restrictions by regulatory agencies. The aim of our study was to investigate the relationship between VPA avoidance/switch and seizure outcome in women of childbearing potential.,

    Abstract



    Objective


    Valproate (VPA) use in women with idiopathic generalized epilepsy (IGE) who are of reproductive age has been a matter of concern and debate, which eventually led to the recent restrictions by regulatory agencies. The aim of our study was to investigate the relationship between VPA avoidance/switch and seizure outcome in women of childbearing potential.




    Methods


    We retrospectively reviewed data from female patients with IGE, 13‐50 years of age, followed since 1980. We evaluated the prescription habits, and the rate of VPA switch for other antiepileptic drugs (AEDs) and its prognostic implications. Seizure remission (SR) was defined as the absence of any seizure type more than 18 months before the last medical observation. The main aim of the study was to assess (a) possible changes in seizure outcome related to VPA switch for other AEDs, especially in patients planning a pregnancy; and (b) possible differences in SR based on the presence/absence of VPA at last observation.




    Results


    One hundred ninety‐eight patients were included in the study. Overall SR at last medical observation was 62.7%. SR significantly differed between subjects taking and those not taking VPA (P < .001) at last visit. Multiple regression models showed that taking VPA at last medical observation was strongly associated with SR in both the general population (P < .001) and the juvenile myoclonic epilepsy (JME) group (P < .001). Thirty‐six (70.6%) of 51 patients who switched from VPA during follow‐up experienced a clinical worsening. Switching back to VPA was more frequently associated with SR at last observation (P < .001). In those patients who substituted VPA in view of a pregnancy, SR and drug burden (monotherapy vs polytherapy) differed significantly before and after the switch.




    Significance


    Our study suggests that VPA avoidance/switch might be associated with unsatisfactory seizure control in women with IGE who are of childbearing potential. Our findings further highlight the complexity of the therapeutic management of female patients of reproductive age.

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    Cerebrospinal fluid and blood biomarkers of status epilepticus

    Cerebrospinal fluid and blood biomarkers of status epilepticus, Abstract Status epilepticus is a condition resulting either from the failure of the mechanisms responsible for seizure termination or from the initiation of mechanisms that lead to abnormally prolonged seizures and require urgent administration of antiepileptic drugs.,

    Abstract


    Status epilepticus is a condition resulting either from the failure of the mechanisms responsible for seizure termination or from the initiation of mechanisms that lead to abnormally prolonged seizures and require urgent administration of antiepileptic drugs. Refractory status epilepticus requires anesthetics drugs and may lead to brain injury with molecular and cellular alterations (eg, inflammation, and neuronal and astroglial injury) that could induce neurologic sequels and further development of epilepsy. Outcome scores based on demographic, clinical, and electroencephalography (EEG) condition are available, allowing prediction of the risk of mortality, but the severity of brain injury in survivors is poorly evaluated. New biomarkers are needed to predict with higher accuracy the outcome of patients admitted with status in an intensive care unit. Here, we summarize the findings of studies from patients and animal models of status epilepticus. Specific protein markers can be detected in the cerebrospinal fluid and the blood. One of the first described markers of neuronal death is the neuron‐specific enolase. Gliosis resulting from inflammatory responses after status can be detected through the increase of S100‐beta, or some cytokines, like the High Mobility Group Box 1. Other proteins, like progranulin may reflect the neuroprotective mechanisms resulting from the brain adaptation to excitotoxicity. These new biomarkers aim to prospectively identify the severity and development of disability, and subsequent epilepsy of patients with status. We discuss the advantages and disadvantages of each biomarker, by evaluating their brain specificity, stability in the fluids, and sensitivity to external interferences, such as hemolysis. Finally, we emphasize the need for further development and validation of such biomarkers in order to better assess patients with severe status epilepticus.

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    Responsive neurostimulation for regional neocortical epilepsy

    Responsive neurostimulation for regional neocortical epilepsy, Abstract Objective Surgical resection of seizure‐producing brain tissue is a gold standard treatment for drug‐resistant focal epilepsy. However, several patient‐specific factors can preclude resective surgery, including a spatially extensive (“regional”) seizure‐onset zone (SOZ).,

    Abstract



    Objective


    Surgical resection of seizure‐producing brain tissue is a gold standard treatment for drug‐resistant focal epilepsy. However, several patient‐specific factors can preclude resective surgery, including a spatially extensive (“regional”) seizure‐onset zone (SOZ). For such patients, responsive neurostimulation (RNS) represents a potential treatment, but its efficacy has not been investigated in this population.




    Methods


    We performed a multicenter retrospective cohort study of patients (N = 30) with drug‐resistant focal epilepsy and a regional neocortical SOZ delineated by intracranial monitoring who were treated with the RNS System for at least 6 months. RNS System leads were placed at least 1‐cm apart over the SOZ, and most patients were treated with a lead‐to‐lead stimulation pathway. Five patients underwent partial resection of the SOZ concurrent with RNS System implantation. We assessed change in seizure frequency relative to preimplant baseline and evaluated correlation between clinical outcome and stimulation parameters.




    Results


    Median follow‐up duration was 21.5 months (range 6‐52). Median reduction in clinical seizure frequency was 75.5% (interquartile range [IQR] 40%‐93.9%). There was no significant difference in outcome between patients treated with and without concurrent partial resection. Most patients were treated with low charge densities (1‐2.5 µC/cm2), but charge density, interlead distance, and duration of treatment were not significantly correlated with outcome.




    Significance


    RNS is a feasible and effective treatment in patients with drug‐resistant regional neocortical seizures. Prospective studies in larger cohorts are necessary to determine optimal lead configuration and stimulation parameters, although our results suggest that lead‐to‐lead stimulation and low charge density may be effective in some patients.

    , admin,

    Volume change in amygdala enlargement as a prognostic factor in patients with temporal lobe epilepsy: A...

    Volume change in amygdala enlargement as a prognostic factor in patients with temporal lobe epilepsy: A..., Abstract Objective Considering the clinical heterogeneity of temporal lobe epilepsy with amygdala enlargement (TLE‐AE), identifying distinct prognostic subgroups of TLE‐AE has clinical implications. Until now, baseline volume of the enlarged amygdala (EAV) has consistently failed to predict prognosis in TLE‐AE.,

    Abstract



    Objective


    Considering the clinical heterogeneity of temporal lobe epilepsy with amygdala enlargement (TLE‐AE), identifying distinct prognostic subgroups of TLE‐AE has clinical implications. Until now, baseline volume of the enlarged amygdala (EAV) has consistently failed to predict prognosis in TLE‐AE. Based on studies suggesting that patients responsive to antiepileptic drugs (AEDs) exhibit remission of AE on follow‐up imaging, we investigated whether reduction rate of EAV is predictive of long‐term prognosis in TLE‐AE.




    Methods


    Sixty‐one consecutive patients with two separate magnetic resonance imaging (MRI) scans were enrolled. To utilize longitudinally measured biomarkers in prediction, the period beyond the first MRI acquisition was split into two periods: the “observation window” (period between the two MRIs) and “prediction window” (follow‐up period beyond the second MRI). Patients were classified according to their AED responsiveness during the observation window, and AED‐responsive patients were further subdivided by initial seizure frequency: (a) AED‐responsive patients presenting with low‐frequency seizures (<5 seizures/3 mo; Group A, n = 25), (b) high‐frequency seizures (≥5 seizures/3 mo; Group B, n = 23), and (c) patients with poor initial treatment response (Group C, n = 13). Multivariate logistic regression models were constructed for identification of prognostic factors. Along with factors obtained at baseline, factors derived from the observation window (annual percentage change of EAV [APCEAV] and initial AED responsiveness) were also considered as potential predictors.




    Results


    Favorable initial treatment response and faster volume reduction rate (APCEAV ≤ −5.0%/y) were identified as factors predictive of achieving overall seizure freedom. Among the AED‐responsive patients, Group A (low‐frequency seizures) showed slower remission of AE and higher rate of seizure recurrence, whereas Group B (high‐frequency seizures) exhibited faster remission of AE and lower rate of seizure recurrence.




    Significance


    Faster recuperation of AE in patients with initial high‐frequency seizures may be indicative of seizure‐induced changes. As volume reduction rate serves as a prognostic marker in TLE‐AE, short‐term MRI follow‐up may be useful in prognostication.

    , admin,

    A face‐to‐face comparison of the intra‐amygdala and intrahippocampal kainate mouse models of mesial...

    A face‐to‐face comparison of the intra‐amygdala and intrahippocampal kainate mouse models of mesial..., Abstract Objective Intracranial (intrahippocampal or intra‐amygdala) administration of kainate in rodents leads to spatially restricted brain injury and development of focal epilepsy with characteristics that resemble mesial temporal lobe epilepsy. Such rodent models are used both in the search for more effective antiseizure drugs (ASDs) and in the development of antiepileptogenic strategies.,

    Abstract



    Objective


    Intracranial (intrahippocampal or intra‐amygdala) administration of kainate in rodents leads to spatially restricted brain injury and development of focal epilepsy with characteristics that resemble mesial temporal lobe epilepsy. Such rodent models are used both in the search for more effective antiseizure drugs (ASDs) and in the development of antiepileptogenic strategies. However, it is not clear which of the models is best suited for testing different types of epilepsy therapies.




    Methods


    In the present study, we performed a face‐to‐face comparison of the intra‐amygdala kainate (IAK) and intrahippocampal kainate (IHK) mouse models using the same mouse inbred strain (C57BL/6). For comparison, some experiments were performed in mouse outbred strains.




    Results


    Intra‐amygdala kainate injection led to more severe status epilepticus and higher mortality than intrahippocampal injection. In male C57BL/6 mice, the latent period to spontaneous recurrent seizures (SRSs) was short or absent in both models, whereas a significantly longer latent period was determined in NMRI and CD‐1 outbred mice. When SRSs were recorded from the ipsilateral hippocampus, relatively frequent electroclinical seizures were determined in the IAK model, whereas only infrequent electroclinical seizures but extremely frequent focal electrographic seizures were determined in the IHK model. As a consequence of the differences in SRS frequency, prolonged video‐electroencephalographic monitoring and drug administration were needed for testing efficacy of the benchmark ASD carbamazepine in the IAK model, whereas acute drug testing was possible in the IHK model. In both models, carbamazepine was only effective at high doses, indicating ASD resistance to this benchmark drug.




    Significance


    We found a variety of significant differences between the IAK and IHK models, which are important when deciding which of these models is best suited for studies on novel epilepsy therapies. The IAK model appears particularly interesting for studies on disease‐modifying treatments, whereas the IHK model is well suited for studying the antiseizure activity of novel ASDs against difficult‐to‐treated focal seizures.

    , admin,

    Early versus late antiepileptic drug withdrawal following temporal lobectomy

    Early versus late antiepileptic drug withdrawal following temporal lobectomy, Freedom from antiepileptic drugs (AEDs) is an important goal of epilepsy surgery and patients usually consider themselves cured only when the AEDs are completely withdrawn. [1,2] Although this issue of AED withdrawal following epilepsy surgery is very important to patients, there is relative dearth of data about the AED usage following epilepsy surgery., Freedom from antiepileptic drugs (AEDs) is an important goal of epilepsy surgery and patients usually consider themselves cured only when the AEDs are completely withdrawn. [1,2] Although this issue of AED withdrawal following epilepsy surgery is very important to patients, there is relative dearth of data about the AED usage following epilepsy surgery. The practice of AED withdrawal varies across the centers and clinicians remain sharply divided in their practice of AED management following epilepsy surgery [3–5]., admin,

    Disorders of the spinal cord and roots

    Disorders of the spinal cord and roots, I, Introduction

    The distinctive patterns of myelopathy (disorder of the spinal cord) and radiculopathy (disorder of spinal roots) are a direct consequence of the striking anatomy of the spinal cord:

  • its near cylindrical, segmental structure of great length (42–45 cm in adults)

  • the marked proximity of ascending and descending long tracts within the confines of a narrow cross sectional area (the maximum circumference of the cervical enlargement of the cord is approximately 38 mm)

  • enclosure by meninges and vertebral column

  • vulnerable blood supply.

  • Having established that a patient's clinical presentation localises to the spinal cord and/or roots, clues to the pathological diagnosis emerge from the timing of the symptoms (table 1), as is usually the case in neurology.

    Neuroanatomy and specific syndromesSpinal cord

    The relationships of the white matter tracts to one another and to the..., admin,

    BDNF Val66Met Positive Players Demonstrate Diffusion Tensor Imaging Consistent With Impaired Myelination...

    BDNF Val66Met Positive Players Demonstrate Diffusion Tensor Imaging Consistent With Impaired Myelination..., The purpose of this study was to examine the potential effect modifying role of the BDNF Val66Met polymorphism on the association of soccer heading with white matter microstructure. We studied 312 players enrolled in the ongoing Einstein Soccer Study, a longitudinal study of amateur soccer player in New York City and surrounding areas.,

    The purpose of this study was to examine the potential effect modifying role of the BDNF Val66Met polymorphism on the association of soccer heading with white matter microstructure. We studied 312 players enrolled in the ongoing Einstein Soccer Study, a longitudinal study of amateur soccer player in New York City and surrounding areas. At enrollment and 2 years later, total heading in the prior 12 months (12-mo.) was estimated using an established self-report instrument and diffusion tensor imaging (DTI) was performed. Generalized Estimating Equations (GEE) logistic regression models were employed to test effect modification by the BDNF Val66Met polymorphism on the association between 12-mo. heading exposure and DTI. We identified a significant interaction of 12-mo heading*BDNF Val66Met genotype on the presence of low Radial Diffusivity, a DTI marker associated with myelination. Only Met (+) players demonstrated significantly reduced odds of low RD [OR (95 % CI): −2.36 (−3.53, −1.19)] associated with the highest vs. lowest quartile of 12-mo heading exposure. BDNF Val66Met (+) soccer players with long-term exposure to high levels of heading exhibit less low Radial Diffusivity, suggesting impaired re-myelination may be a substrate of the previously reported association between heading and poor functional outcomes in soccer players.

    , admin,

    A Discrete Presynaptic Vesicle Cycle for Neuromodulator Receptors

    A Discrete Presynaptic Vesicle Cycle for Neuromodulator Receptors, Presynaptic inhibition is presently thought to require clustering of neuromodulator receptors at the surface of terminals. Jullié et al. show that opioid receptors are diffusely distributed and delineate an alternate strategy using receptor mobility and local endocytic cycling., Presynaptic inhibition is presently thought to require clustering of neuromodulator receptors at the surface of terminals. Jullié et al. show that opioid receptors are diffusely distributed and delineate an alternate strategy using receptor mobility and local endocytic cycling., admin,