Unveiling autonomic failure in synucleinopathies: Significance in diagnosis and treatment.

Autonomic failure is frequently encountered in synucleinopathies such as multiple system atrophy (MSA), Parkinson's disease (PD), Lewy body disease, and pure autonomic failure (PAF). Cardiovascular autonomic failure affects quality of life and can be life threatening due to the risk of falls and the increased incidence of myocardial infarction, stroke, and heart failure. In PD and PAF, pathogenic involvement is mainly post-ganglionic, while in MSA, the involvement is mainly pre-ganglionic. Cardiovascular tests exploring the autonomic nervous system (ANS) are based on the analysis of continuous, non-invasive recordings of heart rate and digital blood pressure (BP). They assess facets of sympathetic and parasympathetic activities and provide indications on the integrity of the baroreflex arc. The tilt test is widely used in clinical practice. It can be combined with catecholamine level measurement and analysis of baroreflex activity and cardiac variability for a detailed analysis of cardiovascular damage. MIBG myocardial scintigraphy is the most sensitive test for early detection of autonomic dysfunction. It provides a useful measure of post-ganglionic sympathetic fiber integrity and function and is therefore an effective tool for distinguishing PD from other parkinsonian syndromes such as MSA. Autonomic cardiovascular investigations differentiate between certain parkinsonian syndromes that would otherwise be difficult to segregate, particularly in the early stages of the disease. Exploring autonomic failure by gathering information about residual sympathetic tone, low plasma norepinephrine levels, and supine hypertension can guide therapeutic management of orthostatic hypotension (OH).

Social and emotional cognition in patients with severe migraine consulting in a tertiary headache center: A preliminary study.

Twenty-three severe migraine participants were studied to investigate social and emotional cognition features and explore their relationship with depression, anxiety and alexithymia. In comparison to normative data, 74% were under the norm for the Faux Pas subtest, 13% for the facial emotion recognition subtest and 52% for the overall composite score of the mini-SEA. Factor 1, Factor 3, and the total score of the TAS-20 were negatively correlated with the Faux Pas subtest. Our preliminary study shows that severe migraine patients present difficulties in inferring mental states, which could be related to alexithymia. It would be useful to identify these impairments in order to improve the quality of care provided. Clinical Trials registration number: NCT03577548.

Unusual clinical and topographical midbrain stroke revealed by pure sensory disturbance.

We describe a rare midbrain stroke presenting with predominantly sensory symptoms. A 71-year-old woman was hospitalized due to the recurrence of faciobrachial sensory loss. Magnetic resonance imaging showed an infarct involving the right side of the middle portion of midbrain at the level of the inferior colliculus. In our case we tried to make some clinico-anatomical correlations. The main anatomical structures involved were the medial lemniscal tract, the ventral part of the spinothalamic tract and the trigeminothalamic tract. The location of the stroke would suggest there are overlaps between arterial territories of the midbrain. Clinicians should look for midbrain infarcts in cases of pure sensory stroke.

Cadaver study of the topography of the musculotendinous junction of the finger extensor muscles: applicability to tendon rupture following closed wrist trauma.

Rupture of the extensor pollicis longus (EPL) tendon in the wrist is a delayed complication that can occur after wrist injury. Several etiology-related hypotheses have been made to explain these ruptures. The one most commonly accepted is necrosis at the musculotendinous junction of the EPL, which is compressed between the extensor retinaculum and dorsal aspect of the radius. To confirm this hypothesis, we performed an anatomical study to show the close relationship between the extensor retinaculum and the musculotendinous junction of the EPL muscle. We calculated the distance between the musculotendinous junction of the various finger extensor muscles and the proximal edge of the extensor retinaculum. We were able to show that this junction is located under the extensor retinaculum for the extensor indicis (EI) and EPL muscles, but the latter is in the third extensor compartment, which is a tight, confined space. Any pressure increase in this space following trauma, for example, can bring about compartment syndrome at this musculotendinous junction, which some authors have found to be poorly vascularized.

Advantages of susceptibility-weighted magnetic resonance sequences in the visualization of intravascular thrombi in acute ischemic stroke.

BACKGROUND: In gradient echo magnetic resonance imaging (MRI), intravascular thrombi (IT) can appear as vascular susceptibility artifacts, linked to local presence of intra-arterial deoxyhaemoglobin, and called susceptibility vessel signs (SVS). AIMS: Our objectives were to evaluate the sensitivity of susceptibility-weighted sequences, such as T2* weighted angiography (SWAN) in the visualization of SVS compared with T2*, to consider whether it enabled a better understanding of the importance of SVS, and to compare cerebral circulation regulation profiles according to the localization of the SVS (i.e. proximal or distal). METHODS: We prospectively studied the clinical and imaging data of 78 consecutive patients admitted for acute cerebral ischemia to the stroke unit of Besançon University Hospital between 1 April 2009 and 31 January 2010. RESULTS: An SVS was visualized in 44/78 (56%) patients using SWAN and in 13/78 (16%) patients using T2*. All the SVS visible using T2* were also visible on the SWAN. The inter-observer kappa score was 0·72 [CI (0·53-0·91)] for T2*, 0·72 [CI (0·57-0·87)] for SWAN, and weighted kappa was 0·77 [CI (0·61-0·92)] for both T2* and SWAN. When an MCA occlusion was visible on MRA imaging (22/78 patients), a SVS was visualized in 7/22 cases (31·8%) using T2* and in 20/22 cases (91%) using SWAN. When the occlusion was visible in the M1 or M2 segments (17/78 patients), an SVS was visualized in 6/17 cases (35·3%) using T2* and in 15/17 cases (88·2%) using SWAN. When the occlusion was visible in the M3 segment (5/78 patients), an SVS was visualized in 1/5 cases (20%) using T2* and in 5/5 cases (100%) using SWAN. Presence of SVS was not associated with cardioembolic etiology of the stroke. CONCLUSIONS: SWAN was more sensitive than T2* in the visualization of SVS in the intracranial arteries during the acute phase of ischemic stroke. Our study shows that the low number of SVS visualized using T2* in previous studies is probably related to a lack of sensitivity of the sequence, rather than to the nature or age of the thrombus. The greater sensitivity of SWAN seems to be linked to the visualization of SVS in cases of small thrombi.

EVER2 protein binds TRADD to promote TNF-α-induced apoptosis.

EVER1 and 2 confer resistance to cutaneous oncogenic human papillomavirus infections by downregulating the activating protein 1 (AP-1) signaling pathway. Defects in their expression are associated with susceptibility to epidermodysplasia verruciformis, which is characterized by persistent ß-HPV infection, tumor necrosis factor alpha (TNF-α) overproduction in keratinocytes and the development of skin cancers. TNF-α-induced apoptosis is a key defense strategy, preventing the persistence of the virus within cells, but the role of EVER proteins in this cell death mechanism triggered by extrinsic stimuli is unknown. We show here that EVER2 induces TNF-α- and TRAIL-dependant apoptosis. It interacts with the N-terminal domain of TRADD, impairs the recruitment of TRAF2 and RIPK1 and promotes apoptosis. The skin cancer-associated EVER2 I306 allele results in an impaired TRADD-EVER2 interaction, with lower levels of cell death following treatment with TNF-α. These data highlight a new, critical function of EVER2 in controlling cell survival in response to death stimuli.

[Toxocara canis cerebral vasculitis revealed by iterative strokes]. / Vascularite cérébrale àToxocara canis révélée par des AVC itératifs.

INTRODUCTION: Cerebral vasculitis is a rare and severe condition, posing problems for diagnosis and treatment. Toxocara canis cerebral vasculitis is exceptionally rare, with only 4 cases having been reported. We report an additional case revealed by iterative strokes. OBSERVATION: A 49-years-old Laotian man presented with right ACA infarction associated with contrast enhancement of cerebrospinal fluid, and multiple segmental stenoses in small and medium caliber encephalic arteries, in a context of hypereosinophilia and chronic headaches. Laboratory tests showed lymphocytic meningitis and T. canis antibody IgE in the blood and CSF. The diagnosis of T. canis cerebral vasculitis was retained. During follow-up, the patient presented again with left pontine hemorrhagic stroke. Conventional cerebral angiography confirmed progression of vasculitis despite treatment. CONCLUSION: This case-report illustrates the diagnostic and therapeutic difficulties associated with vasculitis.

[Cerebellar infarction]. / Les infarctus cérébelleux.

Cerebellar infarction can be difficult to diagnose because the clinical picture is often dominated by fairly non-specific symptoms, which are more indicative of a benign condition. When cerebellar infarction affects the brainstem, the semiology is richer, and pure cerebellar signs are rendered less important. A perfect knowledge of the organisation of the cerebellar artery territories is required, regardless of the infarct topography. This knowledge is essential for making an accurate diagnosis, understanding the mechanisms and organising a treatment plan. Clinical algorithms for the treatment of dizziness, headaches and vomiting would improve the selection of candidates for brain imaging. Thus, the early identification of patients with a high risk of subsequent deterioration would lead to a better prognosis in cases of cerebellar artery territory infarction.

[Functional organisation of the cerebellum: a neuroanatomical approach]. / Organisation fonctionnelle du cervelet: approche neuro-anatomique.

Knowledge of the functional organisation of the cerebellum has progressed. The phylogenetic and anatomical divisions within the cerebellum, which have long been used to describe cerebellar functions, are now too simplistic. The understanding of cerebellar motor functions requires knowledge of a neuroanatomical division based on the afferents and the corticonuclear organisation of the cerebellum. Non-motor cerebellar functions are even more poorly systematised, but the rapid progress being made in neuroscience and neuroimaging techniques should enable them to be better understood.

[Anatomy and physiology of the lower urinary tract]. / Bases anatomo-fonctionnelles du bas appareil urinaire.

Neurogenic lower urinary tract dysfunction is frequent, due to lesions of the central and/or peripheral somatic and/or autonomic nervous system whose role is to ensure the regulation and control of lower urinary tract function. Due to the presence of both smooth and striated muscle cells in structures of the lower urinary tract, nerve pathways and nerve centres belong to both the somatic and autonomic nervous systems.

[Lower urinary tract dysfunction and herniated disk]. / Troubles vésico-sphinctériens et hernies discales.

Lower urinary tract dysfunction related to herniated disk can raise complex diagnostic and management problems. This article reviews the two main clinical situations encountered: documented lower urinary tract dysfunction in a context of cauda equina syndrome secondary to herniated disk and lower urinary tract dysfunction representing the only clinical sign of herniated disk with no other alteration of the neurological examination. Regardless of the neurological signs, urodynamic assessment is essential to characterize any lower urinary tract dysfunction and to determine the modalities of long-term surveillance.

Pontomedullary sulcus infarct: a variant of lateral medullary syndrome.

With the advent of magnetic resonance imaging (MRI) technology, it is now possible to identify and determine the precise location of medullary infarcts. The lateral part of the medulla is most commonly affected by infarction. Classifications of lateral medullary infarcts are usually based on anatomical data, using rostrocaudal and dorsoventral axes to establish correlations with clinical symptoms. Different subtypes of lateral medullary syndrome, depending on location, shape and size of the infarct, have been described in the literature. We report a rare case of a patient presenting with an unusual clinical picture in relation to an infarct specifically located in the lateral part of the pontomedullary sulcus.

Impaired cardiovascular autonomic control in newly and long-term-treated patients with Parkinson's disease: involvement of L-dopa therapy.

In idiopathic Parkinson's disease (PD), autonomic dysfunction is frequent, causing orthostatic hypotension. The respective roles of disease progression and dopaminergic treatment remain unclear. In this study, we investigated the autonomic control of cardiovascular functions and its relation to L-dopa therapy in both newly diagnosed (ND) and long-term-treated (LT) patients. Study subjects were: (1) nine ND patients never having undergone treatment with L-dopa; (2) 18 LT patients who had been receiving L-dopa treatment for a long period. ND patients were investigated before L-dopa treatment and after stabilization of their L-dopa dosage. LT patients were investigated once with their regular treatment and once after a 12-h interruption of L-dopa treatment; (3) nine healthy subjects served as controls. At each test session, blood pressure (BP), heart rate (HR), plasma catecholamines, heart rate variability (HRV), and spontaneous baroreflex sensitivity were assessed in the supine and upright positions. Before receiving L-dopa medication, ND patients had reduced E/I ratios (HR response/deep breathing) and lowered HRV when compared to controls; this was evidence of early effects of the disease on autonomic HR control. Introduction of L-dopa treatment reduced BP, HR, and plasma levels of adrenaline and noradrenaline. Similar changes were found in LT patients when contrasting the short-term treatment interruption and the usual L-dopa dosage. The treatment-linked increase in plasma dopamine also correlated with the decrease in noradrenaline. These results showed that mild impairment of autonomic cardiovascular control occurred early in the course of PD. They also provided evidence that the side effects of L-dopa aggravated the impairment of the autonomic control of BP and HR.

[Evaluation of neurological deficits]. / Exploration d'un deficit neurologique.

The first step in the evaluation of patients with neurological deficit is to obtain expert clinical evaluation to achieve accurate and complete characterization. The type of neurological deficit, its mode of onset, the presence or absence of associated signs and symptoms, and a differential diagnosis must first be described. This will allow identification of the probable site of CNS involvement and appropriate imaging evaluation to be performed. A multi-disciplinary approach with constant correlation between clinical, imaging and pathological findings will enable clinicians to provide patients accurate diagnoses, appropriate prognostic evaluation and optimal management.

Post-transcriptional regulation of inducible nitric oxide synthase in chronic lymphocytic leukemia B cells in pro- and antiapoptotic culture conditions.

Functional inducible NOS (iNOS) may be involved in the prolonged lifespan of chronic lymphocytic leukemia cells (B-CLL), although the exact mechanisms implicated remain elusive as yet. In this work, we have examined iNOS expression in normal B lymphocytes and B-CLL cells in pro- and antiapoptotic conditions. Our results demonstrate: (1) The existence of a new splice variant characterized by a complete deletion of exon 14 (iNOS 13-16(14del)), which was preferentially detected in normal B lymphocytes and may represent an isoform that could play a role in the regulation of enzyme activity. (2) The existence of another alternatively spliced iNOS mRNA transcript involving a partial deletion of the flavodoxin region (iNOS 13-16(neg)) was correlated to a decreased B-CLL cell viability. The 9-beta-D-arabinofuranosyl-2-fluoradenine or fludarabine (F-ara) treatment induced iNOS 13-16(neg) transcript variants, whereas IL-4 enhanced both the transcription of variants, including these exons (iNOS 13-16(pos)), and the expression of a 122 kDa iNOS protein. These results suggest that in B-CLL, a regulation process involving nitric oxide (.- NO) levels could occur by a post-transcriptional mechanism mediated by soluble factors. Our results also provide an insight into a new complementary proapoptotic action of F-ara in B-CLL by the induction of particular iNOS splice variants, leading to the activation of a caspase-3-dependent apoptotic pathway.

Arterial vascularization of the human thalamus: extra-parenchymal arterial groups.

The problem of the arterial vascularization of the human thalamus has been debated at length. Anatomical references concerning the thalamic arterial groups are contradictory and complex, preventing any solid application in practice. It is, therefore, difficult to produce reliable anatomical radio-clinical correlation. In this work, 12 adult human cerebellums (24 hemispheres) were dissected after intra-vascular injection. With care for clarification and standardization, the extra-parenchymal thalamic arteries were classified in six groups: pre-mamillary artery, perforating thalamic arteries, thalamo-geniculate arteries, perforating branches of the postero-medial, postero-lateral and anterior choroidal arteries. Variations in the pre-mamillary artery were rare. The origin of the perforating thalamic artery was unilateral in two of three cases. The origin of the thalamo-geniculate arteries arose between the posterior cerebral artery (53%) and the posterior choroidal arteries (43%). The postero-median choroidal artery was most often single and usually gave the perforating branches for the medial aspect of the thalamus. The postero-lateral choroidal artery was frequently multiple and essentially gave the perforating branches for the superior aspect of the thalamus. The pulvinarian branches most often rose from the postero-lateral choroidal arteries (two thirds of cases) and more rarely from the postero-median choroidal arteries (one third of cases). The anterior choroidal artery is a source of thalamic vascularization by its cisternal branches running towards the lateral thalamus. It can also participate in the vascularization of the pulvinar by the plexiform branches crossing the temporal horn of the lateral ventricle. This study has allowed definition of the intra-parenchymatous arterial map of the thalamus. This mapping is essential for producing anatomical radio-clinical correlations which are pertinent for therapeutic decisions.

"Mesorectum": the surgical value of an anatomical approach.

The quality of total extirpation of the "mesorectum" nowadays determines the prognosis of rectal cancer but the planes of surgical dissection which have been proposed and the anatomical restrictions of this "mesorectum" are sometimes contradictory. The aim of this study was to clarify the relationships of the "mesorectum" with the fascias and nerves of the pelvic cavity to harmonize the plane of dissection in its total extirpation. Four pelvises (2 male, 2 female) harvested from embalmed cadavers were studied by dissection and anatomico-imaging correlation. Two pelvises (1 male, 1 female) were injected with copolymer via the internal iliac and inferior mesenteric arteries. They were then frozen and sectioned sagittally into two hemi-pelvises for the dissection. The two other pelvises were initially studied in 5 mm cuts with CT scanning and magnetic resonance scanning in the sagittal and "transverse oblique" planes. They were then frozen and then cut sagittally into two hemi-pelvises. Each hemi-pelvis was then cut into anatomical sections with an electric saw similar to the radiological cuts: sagittal cuts on the right hemi-pelvis, and "transverse oblique" cuts on the left hemi-pelvis. It was noted that the "mesorectum" was carpeted behind and laterally by a postero-lateral fibrous envelope belonging to the pelvic visceral fascia and in front by a recto-genital membrane of variable nature corresponding to the "Denonvilliers fascia". The postero-lateral fibrous envelope splits into two leaves (anterior and posterior) in front of the sacral concavity and constitutes, lateral to the rectum, the armature of the pelvic plexus. These two leaves delineated the avascular retro-rectal space. The results of the correlations were deceptive. Their use was limited by dilatation of the rectum, which flattened the perirectal fat onto the pelvic walls on all the sections. Nonetheless, the description of the "mesorectum" and the demonstration of its enveloping fascias by dissection allowed the development of a dissection plane for its total extirpation.