Paradoxical Lesions Research Articles

Implementation of a Teledermatology Electronic Consultation Program to Improve the Care of Patients with Inflammatory Bowel Disease.

Skin lesions are a common extraintestinal manifestation associated with inflammatory bowel disease (IBD), although they may also appear as a complication of IBD treatment. Prompt referral to the dermatologist can be very helpful in practice. Teledermatology complements the traditional in-person health care modality, improving access to dermatological care. To evaluate the impact of a store-and-forward teledermatology electronic consultation (e-consult) program on the care of IBD patients. A retrospective study assessing the outcomes of our teledermatology program over its first 2 years of implementation. A total of 39 consultations involving 33 patients (69.2% women, mean age 39.6 years [12-63]) were conducted. The mean number of teleconsultations was 2.8 per month in the initial implementation stage: 33 consultations were carried out in patients with Crohn's disease and 6 in ulcerative colitis. Only 18% of the patients had an active flare-up. The most frequent reason for the e-consult was paradoxical psoriasiform lesions (n = 13, 33.3%), commonly related with anti-tumor necrosis factor agents (70% of the patients) and hidradenitis suppurativa (n = 4, 10.3%). Resolution was achieved in 87% of patients, with a mean waiting time of 4.7 days (0-14). Almost all patients (97%) were satisfied with our program, and considered the referral through the program to be appropriate (92%). Best valued features were the reduced waiting time and the coordinated approach between the two departments involved. Dermatology e-consult is an efficient and useful means of optimizing IBD patient care.

Paradoxical lesions, plasticity and active inference.

Paradoxical lesions are secondary brain lesions that ameliorate functional deficits caused by the initial insult. This effect has been explained in several ways; particularly by the reduction of functional inhibition, or by increases in the excitatory-to-inhibitory synaptic balance within perilesional tissue. In this article, we simulate how and when a modification of the excitatory–inhibitory balance triggers the reversal of a functional deficit caused by a primary lesion. For this, we introduce in-silico lesions to an active inference model of auditory word repetition. The first in-silico lesion simulated damage to the extrinsic (between regions) connectivity causing a functional deficit that did not fully resolve over 100 trials of a word repetition task. The second lesion was implemented in the intrinsic (within region) connectivity, compromising the model’s ability to rebalance excitatory–inhibitory connections during learning. We found that when the second lesion was mild, there was an increase in experience-dependent plasticity that enhanced performance relative to a single lesion. This paradoxical lesion effect disappeared when the second lesion was more severe because plasticity-related changes were disproportionately amplified in the intrinsic connectivity, relative to lesioned extrinsic connections. Finally, this framework was used to predict the physiological correlates of paradoxical lesions. This formal approach provides new insights into the computational and neurophysiological mechanisms that allow some patients to recover after large or multiple lesions.

P192 TELEDERMA: telemedicine system for dermatological lesions in patients with inflammatory bowel disease

Abstract Background Dermatological lesions are a common extra-intestinal manifestation (EIM) associated with inflammatory bowel disease (IBD) or its treatment. The severity of the lesions requires a preferential assessment by the dermatologist. The photography allows a telematic evaluation and non-face-to-face analysis. There are no published experiences of telemedicine in patients with IBD and dermatological EIMs. This study aimed to assess the results of a telematic system for the evaluation of dermatological lesions in patients with IBD (TELEDERMA) developed between the Dermatology Department and IBD Unit. Methods The retrospective study that evaluates this system from its implementation in June 2014 to December 2017 (3.5 years). TELEDERMA (TD) establishes the issuance of a telematic consultation with images through electronic clinical history. A therapy is advised by a dermatologist either through an electronic prescription or a personal appointment. The study evaluates the average time of the telematic consultation, type of lesion and attitude of patients towards the therapy, type and characteristics of the IBD, treatments applied, other EIMs, smoking and dermatological history. Patients were asked to describe and evaluate their level of satisfaction. Results A total number of 47 consultations from 39 patients (70% females) with an average age of 33.2 (8–75) have been made.41 of these consultations were made in patients with Crohn Disease (CD) and 6 in patients with ulcerative colitis (UC). Sixty-seven per cent of the patients with UC had pancolitis. CD Patients had ileal o ileocolonic location (82%) with inflammatory (39%) and stricturing (55%) behaviour. Eighteen per cent of the patients had an active flare-up. 1 out of every four patients had other EIMs. The most frequent reason for teleconsultation was paradoxical psoriasiform lesions (n = 13, 33.3%) of anti-TNF agents (70% of the patients) and suppurative hidradenitis (n = 4, 10.3%). The resolution was achieved in 87%, and only one patient had to interrupt the anti-TNF therapy. The average waiting time was 4.7 days (0–14), compared with the 60 and 28 days of the current waiting list with a routine or preferential request, respectively. All the patients evaluated this system positively, highlighting the advantages of rapidness in both the resolution of the consultations. Conclusion TD is a useful tool for the rapid assessment of dermatological lesions associated with IBD. It prevents the patients from going to the emergency department, improves the care quality and the degree of satisfaction of the patients. The most frequent teleconsultations were related to psoriasiform lesions associated with anti-TNF therapy. The interruption of treatment was exceptional.

Paradoxical skin lesions induced by anti-TNF-α agents in SAPHO syndrome.

The objectives of the study were to characterize the clinical picture of paradoxical skin lesions in SAPHO patients treated with anti-TNF-α agents and to explore its pathogenesis. Patients treated with anti-TNF-α therapy were identified from a cohort of 164 SAPHO patients. The clinical data and skin biopsies were collected. The usage, efficacy, and side effects of anti-TNF-α therapy were recorded. Forty-one (25.0%) patients received anti-TNF-α therapy, of which seven (17.1%) developed paradoxical skin lesions after 1 to 14 infusions. Patients with such lesions were older at onset of skin lesions than those without (p = 0.034). Expression of TNF-α in palmoplantar pustulosis increased after anti-TNF-α therapy in the two examined patients with exacerbated skin lesions. Anti-TNF-α therapy induces paradoxical skin lesions in 17.1% SAPHO patients. Late onset of skin manifestations is associated with an increased risk of such lesions. The paradoxical elevation of TNF-α expression in lesions may contribute to this phenomenon.

Paradoxical psoriasiform reactions of anti-tumour necrosis factor therapy in inflammatory bowel disease patients.

Anti-tumour necrosis factor (TNF) agents have demonstrated efficacy in inflammatory bowel disease (IBD). Cutaneous reactions such as new onset psoriasis or psoriasiform-like reactions are among the most common adverse reactions. We retrospectively identified cases of anti-TNF-induced psoriasis or psoriasiform manifestations in IBD patients at a tertiary centre in Australia. A total of 10 (six females) of 270 (3.7%) IBD patients treated with anti-TNF therapy developed drug-induced psoriatic or psoriasiform-like reactions: five patients were treated with infliximab and five with adalimumab; nine had Crohn disease. The time from initiation of anti-TNF agent to onset of rash was 7.5 months on average. The most frequent distributions were the scalp (7/10) and extremities (6/10). Three patients discontinued anti-TNF treatment with resolution of the rash. Topical treatment of the lesions allowed continued use of biological agent in the majority. Paradoxical psoriatic lesions are recognised adverse events associated with anti-TNF therapy, but discontinuation of therapy due to dermatological complications is required only rarely, even in patients with psoriasiform lesions.

Infliximab-induced skin manifestations in patients with inflammatory bowel disease

Objective The use of infliximab in rheumatoid and inflammatory bowel diseases (IBD) has been associated with a variety of adverse skin reactions, including paradoxical psoriatic lesions. The prevalence and possible predictors for these lesions were under observation in our cross-sectional prospective study. Material and methods Nurses screened the skin of 118 adult patients with IBD during infliximab infusions between 4 September 2013 and 30 September 2014 based on the structured questionnaire. Data on skin manifestations, concomitant medications, extraintestinal manifestations and inflammatory markers were collected for analysis. Results Non-infectious skin manifestations were observed in 27 (22.9%) patients during the study period, of which eight (29.6%) were new-onset, eight (29.6%) were exacerbations of existing lesions and 11 (40.7%) were baseline lesions that did not worsen during the study. Scaling eczema was the most commonly described skin manifestation (n = 8; 29.6%), followed by exacerbated atopic eczema (n = 5; 18.5%) and plausible infliximab-induced psoriasiform lesions (n = 5; 18.5%). The strongest associating factor for skin manifestations was Crohn’s disease, in nearly 80% of afflicted patients. Conclusions Anti-TNF-α therapy is frequently associated with newly onset skin reactions, most commonly in patients with Crohn’s disease. Non-infectious skin manifestations can be treated topically and do not require cessation of anti-TNF-α therapy.

Persistent Trigeminal Artery Variant: MR Angiographic Demonstration

A variant (PTAV) is the persistence after birth of the fetal carotid-basilar anastomosis between the internal carotid artery and a cerebellar artery. We describe two cases of a PTAV demonstrated on MR angiography. A comparison with a persistant trigeminal artery is made and an explanation of the extended Saltzman classification is given. These variants have only little clinical significance, but their recognition is crucial before surgical or interventional procedures or to understand paradoxical cerebellar lesions. MRA appears inferior to selective angiography in diagnosing these variants.

PERSISTENT TRIGEMINAL ARTERY TERMINATING IN THE POSTERIOR INFERIOR CEREBELLAR ARTERY

Persistent trigeminal arteries are rare and represent a remnant of the fetal carotid-basilar circulation. They typically extend from the internal carotid artery to the basilar artery. An unusual case of a patient with a trigeminal artery originating from the internal carotid artery and terminating as the dominant hemispheric branch of the posterior inferior cerebellar artery is presented. A 66-year-old woman presented to the emergency department with pulsatile tinnitus, increasing left eye pain, proptosis, conjunctival injection, diplopia, and decreased visual acuity. Conventional contrast-enhanced computed tomographic and magnetic resonance imaging demonstrated findings consistent with a left carotid-cavernous fistula. The patient underwent an emergency diagnostic cerebral angiogram. Besides an indirect carotid-cavernous fistula on the left side, a right-sided persistent trigeminal artery terminating as the dominant hemispheric trunk of the posteroinferior cerebellar artery was incidentally noted. The vermian branch of the right posteroinferior cerebellar artery arose from the ipsilateral vertebral artery, whereas duplicate superior cerebellar arteries supplied the left posteroinferior cerebellar artery region. The patient was treated for the indirect carotid-cavernous fistula with detachable platinum coils and N-butyl cyanoacrylate, resulting in the resolution of her symptoms. We report a case of a persistent trigeminal artery supplying only the cerebellar hemisphere. The clinical significance of this anomaly relates to its role in endovascular therapeutic and surgical complications and the paradoxical lesions in the cerebellum that occur as a result of carotid disease. We also discuss the Saltzman classification of persistent trigeminal arteries and their variants.

Differential Glutamate Dehydrogenase (GDH) Activity Profile in Patients with Temporal Lobe Epilepsy

Pathophysiologic mechanisms underlying temporal lobe epilepsy (TLE) are still poorly understood. One major hypothesis links alterations in energy metabolism to glutamate excitotoxicity associated with seizures in TLE. The purpose of this study was to determine whether changes in the activities of enzymes critical in energy and neurotransmitter metabolism contributed to the alterations in metabolic status leading to the excitotoxic effects of glutamate. Activities of four key enzymes involved in energy metabolism and glutamate cycling in the brain [aspartate aminotransferase (AAT), citrate synthase (CS), glutamate dehydrogenase (GDH), and lactate dehydrogenase (LDH)] were measured in anterolateral temporal neocortical and hippocampal tissues obtained from three different groups of medically intractable epilepsy patients having either mesial, paradoxical, or mass lesion-associated temporal lobe epilepsy (MTLE, PTLE, MaTLE), respectively. We found that GDH activity was significantly decreased in the temporal cortex mainly in the MTLE group. A similar trend was recognized in the hippocampus of the MTLE. In all three patient groups, GDH activity was considerably lower, and AAT and LDH activities were higher in cortex of MTLE as compared with the corresponding activities in hippocampus (p<0.05). In the MTLE cortex and hippocampus, GDH activities were negatively correlated with the duration since the first intractable seizure. Our results support the hypothesis suggesting major alteration in GDH activity mainly in the MTLE group. It is proposed that significant alterations in the enzyme activities may be contributing to decreased metabolism of glutamate, leading to its accumulation.

Spatial neglect and paradoxical lesion effects in the cat — A model based on midbrain connectivity

Spatial visual attention in humans and mammals is severely disrupted after deactivation of specific cortical or subcortical regions. Such dysfunction has frequently been associated with impaired unilateral cortical mechanisms. Alternatively, I propose that essential mechanisms of spatial attention are based on the bilateral competition between subcortical midbrain structures. Consequently, visuospatial hemineglect and hemi-extinction arise from unbalanced bilateral competition. I present a simple mathematical model, based on known connectivity of the cat midbrain, that exemplifies the principle of competition through mutual inter-hemispheric inhibition. The model represents a linear, topographic integration of several cortical and subcortical inputs in the two halves of the feline superior colliculus. Such a system reproduced a variety of neglect symptoms and also explained the paradoxical effects observed in some lesion experiments where the consequences of a primary lesion could be reversed through a secondary lesion in structures of the contralateral hemisphere. The model generated predictions for future experiments.

Models of paradoxical lesion effects and rules of inference for imputing function to structure in the brain

Studies of the effects of brain lesions on behaviour have informed brain sciences for more than 100 years. Paradoxical results from some experiments, however, contradict widely accepted logic for imputing function to structure, including the `gold standard'; double dissociation. Orienting systems have produced clear examples of paradoxical lesion effects and provide the opportunity to identify reliable inference for imputing function. Our models reproduced the experimental effects. Analysis of the models demonstrated why single and double dissociation studies do not yield reliable conclusions, but suggested more reliable methods for understanding the delegation of functions to neuroanatomical structures in large-scale neural networks.

Cerebral distribution of contrast medium and paradoxical location of lesions of the blood-brain barrier in the rabbit.

Lesions to the blood-brain barrier have been investigated in rabbits following constant or intermittent injections of sodium metrizoate into the internal carotid artery at different injection rates. Under certain experimental conditions the lesion to the blood-brain barrier was predominantly located to the brain area supplied by the contralateral carotid artery or the vertebral arteries. It is shown by serial angiography that the application time was shorter within the vascular territory of the paradoxical lesion. The results may imply that a mixture of blood and contrast medium is more vulnerable to the blood-brain barrier than contrast medium alone.