The Role of Anatomic Connectivity in Inhibitory Control Revealed by Combining Connectome-based Lesion-symptom Mapping with Event-related Potentials.

Inhibitory control refers to the ability to suppress cognitive or motor processes. Current neurocognitive models indicate that this function mainly involves the anterior cingulate cortex and the inferior frontal cortex. However, how the communication between these areas influence inhibitory control performance and their functional response remains unknown. We addressed this question by injecting behavioral and electrophysiological markers of inhibitory control recorded during a Go/NoGo task as the 'symptoms' in a connectome-based lesion-symptom mapping approach in a sample of 96 first unilateral stroke patients. This approach enables us to identify the white matter tracts whose disruption by the lesions causally influences brain functional activity during inhibitory control. We found a central role of left frontotemporal and frontobasal intrahemispheric connections, as well as of the connections between the left temporoparietal and right temporal areas in inhibitory control performance. We also found that connections between the left temporal and right superior parietal areas modulate the conflict-related N2 event-related potential component and between the left temporal parietal area and right temporal and occipital areas for the inhibition P3 component. Our study supports the role of a distributed bilateral network in inhibitory control and reveals that combining lesion-symptom mapping approaches with functional indices of cognitive processes could shed new light on post-stroke functional reorganization. It may further help to refine the interpretation of classical electrophysiological markers of executive control in stroke patients.

Acute right opercular stroke-associated polyopic heautoscopy and hallucinations caused by disconnection to the inferior parietal lobule through the superior longitudinal fasciculus III: A single case study.

Illusory neuropsychiatric symptoms such as hallucinations or the feeling of a presence (FOP) can occur in diffuse brain lesion or dysfunction, in psychiatric diseases as well as in healthy individuals. Their occurrence due to focal brain lesions is rare, most probably due to underreporting, which limits progress in understanding their underlying mechanisms and anatomical determinants. In this single case study, an 86-year-old patient experienced, in the context of an acute right central opercular ischemic stroke, visual hallucinatory symptoms (including palinopsia), differently lateralized auditory hallucinations and FOP. This unusual clinical constellation could be precisely documented and illustrated while still present, allowing a realistic and immersive visual experience validated by the patient. The acute stroke appeared to be their most plausible cause (after exclusion of other etiologies). Furthermore, accurate analysis of tractographic data suggested that disruption in the posterior bundle of the superior longitudinal fasciculus connecting the stroke lesion to the inferior parietal lobule was the anatomical substrate explaining the FOP and, indirectly, also hallucinations through whiter matter involvement, in coherence with existing literature. We could finally elaborate on symptoms taxonomy and phenomenology (e.g., polyopic heautoscopy, hallucinatory FOP, etc), and on patient's remarkable distancing from them (with some therapeutic implications supported by plausibly engaged mechanisms). This case not only authentically enriched the description of such rare combination of heterogenous illusory symptoms through this novel visualization-based reporting approach, but disclosed an unrevealed anatomo-clinical link relating all of them to the acute stroke lesion through an association fiber, thereby contributing to the understanding of these intriguing symptoms and their determinants.

EEG Beta functional connectivity decrease in the left amygdala correlates with the affective pain in fibromyalgia: A pilot study.

Fibromyalgia (FM) is a major chronic pain disease with prominent affective disturbances, and pain-associated changes in neurotransmitters activity and in brain connectivity. However, correlates of affective pain dimension lack. The primary goal of this correlational cross-sectional case-control pilot study was to find electrophysiological correlates of the affective pain component in FM. We examined the resting-state EEG spectral power and imaginary coherence in the beta (ß) band (supposedly indexing the GABAergic neurotransmission) in 16 female patients with FM and 11 age-adjusted female controls. FM patients displayed lower functional connectivity in the High ß (Hß, 20-30 Hz) sub-band than controls (p = 0.039) in the left basolateral complex of the amygdala (p = 0.039) within the left mesiotemporal area, in particular, in correlation with a higher affective pain component level (r = 0.50, p = 0.049). Patients showed higher Low ß (Lß, 13-20 Hz) relative power than controls in the left prefrontal cortex (p = 0.001), correlated with ongoing pain intensity (r = 0.54, p = 0.032). For the first time, GABA-related connectivity changes correlated with the affective pain component are shown in the amygdala, a region highly involved in the affective regulation of pain. The ß power increase in the prefrontal cortex could be compensatory to pain-related GABAergic dysfunction.

Response to experimental cold-induced pain discloses a resistant category among endurance athletes, with a distinct profile of pain-related behavior and GABAergic EEG markers: a case-control preliminary study.

Pain is a major public health problem worldwide, with a high rate of treatment failure. Among promising non-pharmacological therapies, physical exercise is an attractive, cheap, accessible and innocuous method; beyond other health benefits. However, its highly variable therapeutic effect and incompletely understood underlying mechanisms (plausibly involving the GABAergic neurotransmission) require further research. This case-control study aimed to investigate the impact of long-lasting intensive endurance sport practice (≥7 h/week for the last 6 months at the time of the experiment) on the response to experimental cold-induced pain (as a suitable chronic pain model), assuming that highly trained individual would better resist to pain, develop advantageous pain-copying strategies and enhance their GABAergic signaling. For this purpose, clinical pain-related data, response to a cold-pressor test and high-density EEG high (Hß) and low beta (Lß) oscillations were documented. Among 27 athletes and 27 age-adjusted non-trained controls (right-handed males), a category of highly pain-resistant participants (mostly athletes, 48.1%) was identified, displaying lower fear of pain, compared to non-resistant non-athletes. Furthermore, they tolerated longer cold-water immersion and perceived lower maximal sensory pain. However, while having similar Hß and Lß powers at baseline, they exhibited a reduction between cold and pain perceptions and between pain threshold and tolerance (respectively -60% and - 6.6%; -179.5% and - 5.9%; normalized differences), in contrast to the increase noticed in non-resistant non-athletes (+21% and + 14%; +23.3% and + 13.6% respectively). Our results suggest a beneficial effect of long-lasting physical exercise on resistance to pain and pain-related behaviors, and a modification in brain GABAergic signaling. In light of the current knowledge, we propose that the GABAergic neurotransmission could display multifaceted changes to be differently interpreted, depending on the training profile and on the homeostatic setting (e.g., in pain-free versus chronic pain conditions). Despite limitations related to the sample size and to absence of direct observations under acute physical exercise, this precursory study brings into light the unique profile of resistant individuals (probably favored by training) allowing highly informative observation on physical exercise-induced analgesia and paving the way for future clinical translation. Further characterizing pain-resistant individuals would open avenues for a targeted and physiologically informed pain management.

Case Report: Variegate porphyria disclosed by post-gastric bypass complications and causing predominant painful sensorimotor axonal peripheral neuropathy.

Background and aims: Porphyrias constitute a group of rare genetic diseases due to various, mostly autosomal dominant mutations, causing enzymatic deficiency in heme biosynthesis. As a result, neurotoxic porphyrin precursors and light-sensitive porphyrins accumulate, while dysfunction in their targets determines the disease symptoms. Variegate porphyria (VP), one of the acute hepatic porphyrias, is caused by a protoporphyrinogen oxidase (PPOX) mutation. During acute attacks, among other factors, triggered by drugs, stressors, or fasting, an increase in urinary and fecal porphobilinogen (PBG), aminolevulinic acid (ALA), and porphyrins occurs, damaging the autonomous, peripheral, or central nervous system. The disease remains often latent or displays minimal symptoms usually overlooked, exposing undiagnosed patients to potentially serious complications in the presence of the aforementioned triggers. Case report: This 46-year-old woman presented, some days after a bariatric surgery, with severe flaccid tetraparesis and neuropathic pain, initially misdiagnosed as a functional neurological disorder. The severe axonal sensorimotor polyneuropathy led to further investigations, disclosing high urinary porphobilinogen, ALA, and porphyrin levels due to a new PPOX mutation. Retrospectively, it appeared that the patient had had typical VP symptoms (abdominal pain, fragile skin, and dark urine episodes) for years prior to the surgery. Treated with carbohydrate load, neurorehabilitation, and analgesics, she slowly recovered to full mobility, with partial autonomy in her daily life activities, although fatigue and severe pain persisted, preventing her from returning to work. Conclusion: This case documents gastric bypass surgery as a trigger of severe VP invalidating neurological symptoms and illustrates how the delayed diagnosis and post-interventional complications could have been prevented by screening for porphyria cardinal symptoms prior to the intervention. Likewise, this cost-effective screening should be performed before any treatment influencing the diet, which would dramatically improve the porphyria diagnosis rate and outcome.

The Affective Dimension of Pain Appears to Be Determinant within a Pain-Insomnia-Anxiety Pathological Loop in Fibromyalgia: A Case-Control Study.

BACKGROUND: Fibromyalgia (FM) is a chronic pain disease characterized by multiple symptoms whose interactions and implications in the disease pathology are still unclear. This study aimed at investigating how pain, sleep, and mood disorders influence each other in FM, while discriminating between the sensory and affective pain dimensions. METHODS: Sixteen female FM patients were evaluated regarding their pain, while they underwent-along with 11 healthy sex- and age-adjusted controls-assessment of mood and sleep disorders. Analysis of variance and correlations were performed in order to assess group differences and investigate the interactions between pain, mood, and sleep descriptors. RESULTS: FM patients reported the typical widespread pain, with similar sensory and affective inputs. Contrary to controls, they displayed moderate anxiety, depression, and insomnia. Affective pain (but neither the sensory pain nor pain intensity) was the only pain indicator that tendentially correlated with anxiety and insomnia, which were mutually associated. An affective pain-insomnia-anxiety loop was thus completed. High ongoing pain strengthened this vicious circle, to which it included depression and sensory pain. CONCLUSIONS: Discriminating between the sensory and affective pain components in FM patients disclosed a pathological loop, with a key role of affective pain; high ongoing pain acted as an amplifier of symptoms interaction. This unraveled the interplay between three of most cardinal FM symptoms; these results contribute to better understand FM determinants and pathology and could help in orienting therapeutic strategies.

Experience with opioids does not modify the brain network involved in expectations of placebo analgesia.

Placebo analgesia (PA) is defined as a psychobiological phenomenon triggered by the information surrounding an analgesic drug instead of its inherent pharmacological properties. PA is hypothesized to be formed through either verbal suggestions or conditioning. The present study aims at disentangling the neural correlates of expectations effects with or without conditioning through prior experience using the model of PA. We addressed this question by recruiting two groups of individuals holding comparable verbally-induced expectations regarding morphine analgesia but either (i) with or (ii) without prior experience with opioids. We then contrasted the two groups' neurocognitive response to acute heat-pain induction following the injection of sham morphine using electroencephalography (EEG). Topographic ERP analyses of the N2 and P2 pain evoked potential components allowed to test the hypothesis that PA involves distinct neural networks when induced by expectations with or without prior experience. First, we confirmed that the two groups showed corresponding expectations of morphine analgesia (Hedges' gs < .4 positive control criteria, gs = .37 observed difference), and that our intervention induced a medium-sized PA (Hedges' gav ≥ .5 positive control, gav = .6 observed PA). We then tested our hypothesis on the recruitment of different PA-associated brain networks in individuals with versus without prior experience with opioids and found no evidence for a topographic N2 and P2 ERP components difference between the two groups. Our results thus suggest that in the presence of verbally-induced expectations, modifications in the PA-associated brain activity by conditioning are either absent or very small.

An Ecological Monitoring and Management App (EMMA) for Older Adults With Chronic Pain: Protocol for a Design and Feasibility Study.

BACKGROUND: Chronic pain is a complex problem for many older adults that affects both physical functioning and psychological well-being. Mobile health (mHealth) technologies have shown promise in supporting older persons in managing chronic conditions. Cognitive behavior therapy is recommended for older people with chronic pain. However, web-based treatment programs for chronic pain are not aimed at the needs of older people and offer standard therapies without providing tailored treatment for this population. OBJECTIVE: To address this problem, we aim to develop a psychological web-based intervention for ecological monitoring of daily life experiences with chronic pain called EMMA to support self-management of chronic pain in older adults. METHODS: The key clinical and engagement features of the intervention were established through the integration of evidence-based material from cognitive behavioral therapy for the treatment of chronic pain in older adults. The development process uses a co-design approach and actively involves end-users in the design process by incorporating feedback from focus groups with older adults in order to inform a user-centered intervention design. For the co-design process, we will include 10 older adults with chronic pain, who will discuss the requirements for the app in workshops in order to ensure suitability of the app for older adults with chronic pain. In order to test the feasibility and acceptability of the intervention, we will include a sample of 30 older adults with chronic pain who will test all features of the intervention for a period of 8 consecutive weeks. After the trial period, validated instruments will be used to assess usability and acceptability, as well as influence on pain levels and associated physical and psychological symptoms. Participants will be invited to take part in a semistructured telephone interviews after the trial period to explore their experiences using the app. RESULTS: Digitalization of the pain diary and psychotherapeutic content has started. Recruitment of participants for the co-design workshops will start as soon as we have a functioning prototype of the electronic pain diary and EMMA intervention, which is expected to be in September 2021. The feasibility study will start as soon as the co-design process is finished and required changes have been implemented into the pain diary and the EMMA intervention. We expect to start the feasibility study early in 2022. CONCLUSIONS: Required changes to assure usability and acceptability will be directly implemented in the app. EMMA brings together a strong body of evidence using cognitive behavioral and self-management theory with contemporary mHealth principles, allowing for a cost-effective intervention that can be used to target chronic pain anywhere and anytime by older adults. Given the ubiquity of mHealth interventions for chronic conditions, the results of this study may serve to inform the development of tailored self-management interventions. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/26930.

Revisiting Konzo Risk Factors in Three Areas Differently Affected by Spastic Paraparesis in Eastern Democratic Republic of the Congo Discloses a Prominent Role of the Nutritional Status-A Comparative Cross-Sectional Study.

This comparative cross-sectional study aimed to better understand the respective contributions of protein malnutrition and cassava-derived cyanide poisoning in the development of konzo. We compared data on nutritional status and cyanide exposure of school-age adolescent konzo-diseased patients to those of non-konzo subjects of similar age from three areas in the Eastern Democratic Republic of the Congo. Our results show that konzo patients had a high prevalence of both wasting (54.5%) and stunting (72.7%), as well as of cyanide poisoning (81.8%). Controls from Burhinyi and those from Idjwi showed a similar profile with a low prevalence of wasting (3.3% and 6.5%, respectively) and intermediate prevalence of stunting (26.7% and 23.9%, respectively). They both had a high prevalence of cyanide poisoning (50.0% and 63.0%, respectively), similar to konzo-patients. On the other hand, controls from Bukavu showed the lowest prevalence of both risk factors, namely chronic malnutrition (12.1%) and cyanide poisoning (27.6%). In conclusion, cassava-derived cyanide poisoning does not necessarily coexist with konzo outbreaks. The only factor differentiating konzo patients from healthy individuals exposed to cyanide poisoning appeared to be their worse nutritional status. This further suggests that, besides the known role of cyanide poisoning in the pathogenesis of konzo, malnutrition may be a key factor for the disease occurrence.

Konzo risk factors, determinants and etiopathogenesis: What is new? A systematic review.

Konzo is a toxico-nutritional upper motor neuron disease causing a spastic paraparesis in schoolchildren and childbearing women in some African countries. Almost a century since the first description of konzo, its underlying etiopathogenic mechanisms and causative agent remain unknown. This paper aims at refreshing the current knowledge of konzo determinants and pathogenesis in order to enlighten potential new research and management perspectives. Literature research was performed in PubMed and Web of Science databases according to the PRISMA methodology. Available data show that cassava-derived cyanide poisoning and protein malnutrition constitute two well-documented risk factors of konzo. However, observational studies have failed to demonstrate the causal relationship between konzo and cyanide poisoning. Thiocyanate, the current marker of choice of cyanide exposure, may underestimate the actual level of cyanide poisoning in konzo patients as a larger amount of cyanide is detoxified via other unusual pathways in the context of protein malnutrition characterizing these patients. Furthermore, the appearance of konzo may be the consequence of the interplay of several factors including cyanide metabolites, nutritional deficiencies, psycho-emotional and geo-environmental factors, resulting in pathophysiologic phenomena such as excitotoxicity or oxidative stress, responsible for neuronal damage that takes place at sparse cellular and/or subcellular levels.

Beta Electroencephalographic Oscillation Is a Potential GABAergic Biomarker of Chronic Peripheral Neuropathic Pain.

This preliminary investigation aimed to assess beta (ß) oscillation, a marker of the brain GABAergic signaling, as a potential objective pain marker, hence contributing at the same time to the mechanistic approach of pain management. This case-control observational study measured ß electroencephalographic (EEG) oscillation in 12 right-handed adult male with chronic neuropathic pain and 10 matched controls (∼55 years). Participants were submitted to clinical evaluation (pain visual analog scale, Hospital Anxiety, and Depression scale) and a 24-min high-density EEG recording (BIOSEMI). Data were analyzed using the EEGlab toolbox (MATLAB), SPSS, and R. The global power spectrum computed within the low (Lß, 13-20 Hz) and the high (Hß, 20-30 Hz) ß frequency sub-bands was significantly lower in patients than in controls, and accordingly, Lß was negatively correlated to the pain visual analog scale (R = -0.931, p = 0.007), whereas Hß correlation was at the edge of significance (R = -0.805; p = 0.053). Patients' anxiety was correlated to pain intensity (R = 0.755; p = 0.003). Normalization of the low and high ß global power spectrum (GPS) to the GPS of the full frequency range, while confirming the significant Lß power decrease in chronic neuropathic pain patients, vanished the significance of the Hß decrease, as well as the correlation between Lß power and pain intensity. Our results suggest that the GABAergic Lß EEG oscillation is affected by chronic neuropathic pain. Confirming the Lß GPS decrease and the correlation with pain intensity in larger studies would open new opportunities for the clinical application of gamma-aminobutyric acid-modifying therapies.

Long-term effects of severe acute malnutrition during childhood on adult cognitive, academic and behavioural development in African fragile countries: The Lwiro cohort study in Democratic Republic of the Congo.

INTRODUCTION: Little is known about the outcomes of subjects with a history of severe acute malnutrition (SAM). We therefore sought to explore the long-term effects of SAM during childhood on human capital in adulthood in terms of education, cognition, self-esteem and health-related disabilities in daily living. METHODOLOGY: We traced 524 adults (median age of 22) in the eastern Democratic Republic of the Congo, who were treated for SAM during childhood at Lwiro hospital between 1988 and 2007 (median age 41 months). We compared them with 407 community controls of comparable age and sex. Our outcomes of interest were education, cognitive function [assessed using the Mini Mental State Examination (MMSE) for literate participants, or its modified version created by Ertan et al. (MMSE-I) for uneducated participants], self-esteem (measured using the Rosenberg Self-Esteem Scale) and health-related social and functional disabilities measured using the World Health Organization Disability Assessment Schedule (WHODAS). For comparison, we used the Chi-squared test along with the Student's t-test for the proportions and means respectively. RESULTS: Compared with the community controls, malnutrition survivors had a lower probability of attaining a high level of education (p < 0.001), of reporting a high academic performance (p = 0.014) or of having high self-esteem (p = 0.003). In addition, malnutrition survivors had an overall mean score in the cognitive test that was lower compared with the community controls [25.6 compared with 27.8, p = 0.001 (MMSE) and 22.8 compared with 26.3, p < 0.001(MMSE-I)] and a lower proportion of subjects with a normal result in this test (78.0% compared with 90.1%, p < 0.001). Lastly, in terms of health-related disabilities, unlike the community controls, malnutrition survivors had less social disability (p = 0.034), but no difference was observed as regards activities of daily living (p = 0.322). CONCLUSION: SAM during childhood exposes survivors to low human capital as regards education, cognition and behaviour in adulthood. Policy-deciders seeking to promote economic growth and to address various psychological and medico-social disorders must take into consideration the fact that appropriate investment in child health as regards SAM is an essential means to achieve this.

The right thalamic ventral posterolateral nucleus seems to be determinant for macrosomatognosia: a case report.

BACKGROUND: Macrosomatognosiais the illusory sensation of a substantially enlarged body part. This disorder of the body schema, also called "Alice in wonderland syndrome" is still poorly understood and requires careful documentation and analysis of cases. The patient presented here is unique owing to his unusual macrosomatognosia phenomenology, but also given the unreported localization of his most significant lesion in the right thalamus that allowed consistent anatomo-clinical analysis. CASE PRESENTATION: This 45-years old man presented mainly with long-lasting and quasi-delusional macrosomatognosia associated to sensory deficits, both involving the left upper-body, in the context of a right thalamic ischemic lesion most presumably located in the ventral posterolateral nucleus. Fine-grained probabilistic and deterministic tractography revealed the most eloquent targets of the lesion projections to be the ipsilateral precuneus, superior parietal lobule,but also the right primary somatosensory cortex and, to a lesser extent, the right primary motor cortex. Under stationary neurorehabilitation, the patient slowly improved his symptoms and could be discharged back home and, later on, partially return to work. CONCLUSION: We discuss deficient neural processing and integration of sensory inputs within the right ventral posterolateral nucleus lesion as possible mechanisms underlying macrosomatognosia in light of observed anatomo-clinical correlations. On the other hand, difficulty to classify this unique constellation of Alice in wonderland syndrome calls for an alternative taxonomy of cognitive and psychic aspects of illusory body-size perceptions.

Identification of GSK-3 as a Potential Therapeutic Entry Point for Epilepsy.

In view of the clinical need for new antiseizure drugs (ASDs) with novel modes of action, we used a zebrafish seizure model to screen the anticonvulsant activity of medicinal plants used by traditional healers in the Congo for the treatment of epilepsy, and identified a crude plant extract that inhibited pentylenetetrazol (PTZ)-induced seizures in zebrafish larvae. Zebrafish bioassay-guided fractionation of this anticonvulsant Fabaceae species, Indigofera arrecta, identified indirubin, a compound with known inhibitory activity of glycogen synthase kinase (GSK)-3, as the bioactive component. Indirubin, as well as the more potent and selective GSK-3 inhibitor 6-bromoindirubin-3'-oxime (BIO-acetoxime) were tested in zebrafish and rodent seizure assays. Both compounds revealed anticonvulsant activity in PTZ-treated zebrafish larvae, with electroencephalographic recordings revealing reduction of epileptiform discharges. Both indirubin and BIO-acetoxime also showed anticonvulsant activity in the pilocarpine rat model for limbic seizures and in the 6-Hz refractory seizure mouse model. Most interestingly, BIO-acetoxime also exhibited anticonvulsant actions in 6-Hz fully kindled mice. Our findings thus provide the first evidence for anticonvulsant activity of GSK-3 inhibition, thereby implicating GSK-3 as a potential therapeutic entry point for epilepsy. Our results also support the use of zebrafish bioassay-guided fractionation of antiepileptic medicinal plant extracts as an effective strategy for the discovery of new ASDs with novel mechanisms of action.

Definition and management of varicella zoster virus-associated meningoradiculitis: a case report.

BACKGROUND: The varicella zoster virus affects the central or peripheral nervous systems upon reactivation, especially when cell-mediated immunity is impaired. Among varicella zoster virus-related neurological syndromes, meningoradiculitis is an ill-defined condition for which clear management guidelines are still lacking. Zoster paresis is usually considered to be a varicella zoster virus-peripheral nervous system complication and treated with oral antiviral therapy. Yet in the literature, the few reported cases of herpes zoster with mild cerebral spinal fluid inflammation were all considered meningoradiculitis and treated using intravenous antiviral drugs, despite absence of systemic signs of meningitis. Nevertheless, these two clinical pictures are very similar. CASE PRESENTATION: We report the case of an alcohol-dependent elderly Caucasian man presenting with left lower limb zoster paresis and mild cerebral spinal fluid inflammation, with favorable outcome upon IV antiviral treatment. We discuss interpretation of liquor inflammation in the absence of clinical meningitis and implications for the antiviral treatment route. CONCLUSION: From this case report we suggest that varicella zoster virus-associated meningoradiculitis should necessarily include meningitis symptoms with the peripheral neurological deficits and cerebral spinal fluid inflammation, requiring intravenous antiviral treatment. In the absence of (cell-mediated) immunosuppression, isolated zoster paresis does not necessitate spinal tap or intravenous antiviral therapy.

NKCC1 downregulation induces hyperpolarizing shift of GABA responsiveness at near term fetal stages in rat cultured dorsal root ganglion neurons.

BACKGROUND: GABAA receptor-mediated neurotransmission is greatly influenced by cation-chloride cotransporter activity during developmental stages. In embryonic neurons Na-K-2Cl (NKCC1) cotransporters mediate active chloride uptake, thus increasing the intracellular chloride concentration associated with GABA-induced depolarization. At fetal stages near term, oxytocin-induced NKCC1 downregulation has been implicated in the developmental shift from depolarizing to hyperpolarizing GABA action. Mature dorsal root ganglion neurons (DRGN), however, express high NKCC1 levels and maintain high intracellular chloride levels with consequent GABA-induced depolarization. RESULTS: Gramicidin-perforated patch-clamp recordings were used to assess the developmental change in chloride homeostasis in rat cultured small DRGN at the embryonic day 16 (E16) and 19 (E19). The results were compared to data previously obtained in fetal DRGN at E14 and in mature cells. A significant NKCC1 downregulation, leading to reduction in excitatory GABAergic transmission, was observed at E16 and E19. CONCLUSION: These results indicate that NKCC1 activity transiently decreases in DRGN at fetal stages near term. This developmental shift in GABAergic transmission may contribute to fetal analgesia and neuroprotection at birth.

Sweet taste loss in myasthenia gravis: more than a coincidence?

Sweet dysgeusia, a rare taste disorder, may be encountered in severe anti-acetylcholine receptor antibody (AChRAb)-myasthenia gravis (MG). A 42 year-old man reported progressive loss of sweet taste evolving for almost 10 weeks, revealing an AChRAb-positive MG with thymoma. Improvement of sweet perception paralleled reduction of the MG composite score during the 15 months follow up period, with immunosuppressive and surgical treatments. We suggest that sweet dysgeusia is a non-motor manifestation of MG that may result from a thymoma-dependent autoimmune mechanism targeting gustducin-positive G-protein-coupled taste receptor cells, in line with recent data from MRL/MpJ-Fas lpr/ (MRL/lpr) transgenic mice with autoimmune disease.