Nerve entrapment complicating neurogenic thoracic outlet syndrome surgery: A 10-year retrospective study.

Neurogenic thoracic outlet syndrome results from compression of the brachial plexus. The symptoms are mainly pain, upper-limb weakness and paresthesia. Management always starts with a rehabilitation program, but failure of rehabilitation may necessitate surgery. In practice, we observed that several patients developed secondary distal nerve entrapment in the months following surgery, with no preoperative compression. We aimed to assess the occurrence of distal nerve entrapment after surgery for neurogenic thoracic outlet syndrome in a retrospective cohort study. Seventy-four patients were included; 82% females; mean age, 39.4 ± 9.4 years. There were 36.5% with high intensity and 63.5% with low to moderate intensity work. Eighteen (24.3%) developed secondary upper-limb entrapment at 10.6 ± 5.8 months after surgery. Sixteen had a single entrapment and 2 had two different entrapments. In 10 cases (50%) the ulnar nerve was involved at the elbow, in 7 (35.0%) the radial nerve at the radial tunnel, and in 3 (15.0%) the median nerve. No differences were found between patients with and without secondary nerve entrapment in gender (p = 0.51), mean age (p = 0.44), symptom duration (p = 0.92) or work intensity (p = 0.26). Further studies are needed to confirm these results and to shed light on the underlying mechanisms.

Possible role of the botulinum toxin in the management of neurogenic thoracic outlet syndrome: a systematic review.

INTRODUCTION: Thoracic outlet syndrome (TOS) is related to the compression and/or the traction of the upper-limb neurovascular bundle, responsible for a chronic painful impairment. Neurogenic TOS (NTOS) is the most common manifestation. It remains a challenging diagnosis and its treatment is also difficult. Botulinum toxin (BTX) has been described to help both the diagnosis and the symptoms improvement. EVIDENCE ACQUISITION: A systematic literature research was performed using PubMed, ScienceDirect, and Embase databases to collect studies reporting the use of BTX in NTOS management. We followed the PRISMA guidelines, and the included studies were evaluated using the GRADE approach. EVIDENCE SYNTHESIS: We included 10 original articles representing 555 patients. Various outcomes were considered, and results varied from a study to another. Symptoms relief varied from an absence of BTX effectiveness to 84.1% of improvement; relief duration was also reported from none to 88 days. BTX injections were debatable predictors of surgical procedure successes due to low evidence. There was a huge gap between the studies concerning side-effects of the BTX procedures, from none to 100% of the patients. CONCLUSIONS: There is no evidence for considering BTX injection as a validated tool for the management of NTOS. There might be a slight effect on symptoms, but outcomes are very variable, which prevents further interpretations. The use of BTX should be evaluated in larger prospective cohorts with more standardized outcomes.

Outcome of Silicone Implant for Treatment After Failure of Primary Trapeziometacarpal Surgery.

PURPOSE: To evaluate the outcome of a silicone implant used after failure of primary trapeziometacarpal (TMC) surgery. METHODS: We retrospectively reviewed 22 Tie-in silicone implants performed between January 2005 and December 2015. All silicone implants were used for revision after failure of TMC surgery. We determined the time between implantation and the date of diagnosis of the failed revision procedure (rupture, major wear, dislocation, or poor clinical tolerance). RESULTS: Median survival was 2.15 years. Only 3 patients did not show wear, but one was lost after 1 year of follow-up. We found 10 cases with rupture of the implant, 5 with implant instability (subluxation or dislocation), 3 implants with abnormal wear, and 1 patient who reported residual pain. A total of 42% of failures were associated with silicone synovitis CONCLUSIONS: Survival of the Tie-in silicone implant in TMC revision surgery is poor; nearly half of implants failed at 2 years. The rate of silicone synovitis is also important because future revision might be more complex owing to bone loss. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Reconstruction for failed trapeziometacarpal implant.

Trapeziometacarpal prosthesis by metallic implant is used to treat thumb carpometacarpal osteoarthritis. Many causes of failure have been described whereas revision techniques still remain a challenging surgery. In this article, we describe a revision strategy in a failed metallic cemented trapeziometacarpal implant with major first metacarpal shortening.

Microglia in close vicinity of glioma cells: correlation between phenotype and metabolic alterations.

Microglia are immune cells within the central nervous system. In brain-developing tumors, gliomas are able to silence the defense and immune functions of microglia, a phenomenon which strongly contributes to tumor progression and treatment resistance. Being activated and highly motile, microglia infiltrate tumors and secrete macrophagic chemoattractant factors. Thereafter, the tumor cells shut down their immune properties and stimulate the microglia to release tumor growth-promoting factors. The result of such modulation is that a kind of symbiosis occurs between microglia and tumor cells, in favor of tumor growth. However, little is known about microglial phenotype and metabolic modifications in a tumoral environment. Co-cultures were performed using CHME5 microglia cells grown on collagen beads or on coverslips and placed on monolayer of C6 cells, limiting cell/cell contacts. Phagocytic behavior and expression of macrophagic and cytoskeleton markers were monitored. Respiratory properties and energetic metabolism were also studied with regard to the activated phenotype of microglia. In co-cultures, transitory modifications of microglial morphology and metabolism were observed linked to a concomitant transitory increase of phagocytic properties. Therefore, after 1 h of co-culture, microglia were activated but when longer in contact with tumor cells, phagocytic properties appear silenced. Like the behavior of the phenotype, microglial respiration showed a transitory readjustment although the mitochondria maintained their perinuclear relocation. Nevertheless, the energetic metabolism of the microglia was altered, suggesting a new energetic steady state. The results clearly indicate that like the depressed immune properties, the macrophagic and metabolic status of the microglia is quickly driven by the glioma environment, despite short initial phagocytic activation. Such findings question the possible contribution of diffusible tumor factors to the microglial metabolism.

[French innovations in plastic and reconstructive surgery of hand and limbs. Interview by Michel Schoofs]. / La créativité et les innovations françaises en chirurgie plastique reconstructrice et esthétique de la main et des membres.

This unique manuscript reports the interviews of Pr Michel Merle and Jacques Baudet, two figures of the French plastic reconstructive and microsurgical surgery of the limbs. Their testimony shed lights into our past, explains our present and helps foresee our future. The lesson to take away from their story is that no mountain can be overcome in one day, but rather requires countless efforts, dedication and persistence.

[Surgery of the wrist and hand in rheumatoid arthritis]. / Chirurgie du poignet et de la main rhumatoïde.

Wrist and hand surgery in rheumatoid arthritis has continued to evolve since first being tried fifty years ago. Improvements have flowed from a better understanding of pathophysiological mechanisms, from technical progress and from more effective medical treatment. The use of methotrexate and the subsequent development of biological therapies have transformed the course of the disease, increasing the chances of positive and durable surgical results. Priority must be given to re-alignment of the wrist in order to protect the fingers. It is equally important to perform synovectomies of the extrinsic tendons and to re-align extensor tendons with the metacarpophalangeal joints. At a later stage, metacarpophalangeal arthroplasty can re-establish a useful range of mobility in these joints. Early correction of swan-neck deformity is essential. Arthrodesis of the metacarpophalangeal joint of the thumb is also beneficial as it improves finger-thumb pinch grip. These procedures are usually performed under regional block anaesthesia. They take less than two hours and the techniques employed are compatible with early mobilisation. Effective surgical management of rheumatoid arthritis requires close collaboration between surgeons, rheumatologists, physiotherapists, orthotists and occupational therapists. There are thought to be some 500,000 patients in France who might benefit from such treatment but, as yet, there are too few multidisciplinary teams equipped to manage them effectively.

Monitoring demyelination and remyelination by magnetization transfer imaging in the mouse brain at 9.4 T.

OBJECTIVE: The aim of this study was to assess quantitatively structural changes in myelin content occurring during demyelination and remyelination by magnetization transfer imaging (MTI). MATERIALS AND METHODS: In a reversible model of demyelination with no axonal loss, mice intoxicated by cuprizone were studied by MTI in vivo at 9.4 T. MRI data were compared to histopathological examinations. RESULTS: Data revealed that the magnetization transfer ratio (MTR) decreased significantly during demyelination and increased during remyelination with strong correlation to the myelin content (r=0.79, P=0.01). CONCLUSIONS: This study demonstrated that MTR is a sensitive and reproducible quantitative marker to assess myelin loss and repair. This may lead to in vivo monitoring of therapeutic strategies promoting remyelination.

Co-regulation of yeast purine and phosphate pathways in response to adenylic nucleotide variations.

Adenylate kinase (Adk1p) is a pivotal enzyme in both energetic and adenylic nucleotide metabolisms. In this paper, using a transcriptomic analysis, we show that the lack of Adk1p strongly induced expression of the PHO and ADE genes involved in phosphate utilization and AMP de novo biosynthesis respectively. Isolation and characterization of adk1 point mutants affecting PHO5 expression revealed that all these mutations also severely affected Adk1p catalytic activity, as well as PHO84 and ADE1 transcription. Furthermore, overexpression of distantly related enzymes such as human adenylate kinase or yeast UMP kinase was sufficient to restore regulation. These results demonstrate that adenylate kinase catalytic activity is critical for proper regulation of the PHO and ADE pathways. We also establish that adk1 deletion and purine limitation have similar effects on both adenylic nucleotide pool and PHO84 or ADE17 expression. Finally, we show that, in the adk1 mutant, upregulation of ADE1 depends on synthesis of the previously described effector(s) (S)AICAR ((N-succinyl)-5-aminoimidazol-4-carboxamide ribotide), while upregulation of PHO84 necessitates the Spl2p positive regulator. This work reveals that adenylic nucleotide availability is a key signal used by yeast to co-ordinate phosphate utilization and purine synthesis.

Close coupling between astrocytic and neuronal metabolisms to fulfill anaplerotic and energy needs in the rat brain.

Carbon metabolism in the rat brain was studied in animals anesthetized with a light dose of pentobarbital and in awake animals under morphine, which were infused with either [1-13C]glucose+acetate or glucose+[2-13C]acetate for various periods of time. Brain amino-acid enrichments in tissue extracts were determined by nuclear magnetic resonance (NMR) spectroscopy and their time evolution was analyzed by automatic fitting. Acetyl-coenzyme A C2 enrichment and ratio between pyruvate carboxylase and pyruvate dehydrogenase activity (PC/PDH) were determined from glutamate and glutamine labeling. The following results were obtained: (i) amino-acid enrichment patterns implied metabolic compartmentation and occurrence of the glutamate-glutamine cycle; (ii) kinetics of aspartate, GABA, and glutamate labeling from [1-13C]glucose and of glutamine labeling from [2-13C]acetate indicated a twofold higher metabolic activity in awake than in anesthetized rat brain; (iii) evaluation of the contributions of the astrocytic and neuronal metabolisms to glutamine synthesis in both groups of rats indicated a coupling between neuronal tricarboxylic acid (TCA) cycle, glutamate-glutamine cycle and glial TCA cycle; and (iv) analyzing the extrapolations back to time zero and the steady-state values of PC/PDH indicated a close coupling between PC activity and both astrocytic and neuronal TCA cycles. All these results suggest a cooperative-like behavior of astrocytic and neuronal metabolisms to fulfill the anabolic and energy needs linked to brain activation.

Activity-dependent regulation of energy metabolism by astrocytes: an update.

Astrocytes play a critical role in the regulation of brain metabolic responses to activity. One detailed mechanism proposed to describe the role of astrocytes in some of these responses has come to be known as the astrocyte-neuron lactate shuttle hypothesis (ANLSH). Although controversial, the original concept of a coupling mechanism between neuronal activity and glucose utilization that involves an activation of aerobic glycolysis in astrocytes and lactate consumption by neurons provides a heuristically valid framework for experimental studies. In this context, it is necessary to provide a survey of recent developments and data pertaining to this model. Thus, here, we review very recent experimental evidence as well as theoretical arguments strongly supporting the original model and in some cases extending it. Aspects revisited include the existence of glutamate-induced glycolysis in astrocytes in vitro, ex vivo, and in vivo, lactate as a preferential oxidative substrate for neurons, and the notion of net lactate transfer between astrocytes and neurons in vivo. Inclusion of a role for glycogen in the ANLSH is discussed in the light of a possible extension of the astrocyte-neuron lactate shuttle (ANLS) concept rather than as a competing hypothesis. New perspectives offered by the application of this concept include a better understanding of the basis of signals used in functional brain imaging, a role for neuron-glia metabolic interactions in glucose sensing and diabetes, as well as novel strategies to develop therapies against neurodegenerative diseases based upon improving astrocyte-neuron coupled energetics.

Brain pyruvate recycling and peripheral metabolism: an NMR analysis ex vivo of acetate and glucose metabolism in the rat.

The occurrence of pyruvate recycling in the rat brain was studied in either pentobarbital anesthetized animals or awake animals receiving a light analgesic dose of morphine, which were infused with either [1-13C]glucose + acetate or glucose + [2-13C]acetate for various periods of time. Metabolite enrichments in the brain, blood and the liver were determined from NMR analyses of tissue extracts. They indicated that: (i) Pyruvate recycling was revealed in the brain of both the anesthetized and awake animals, as well as from lactate and alanine enrichments as from glutamate isotopomer composition, but only after infusion of glucose + [2-13C]acetate. (ii) Brain glucose was labelled from [2-13C]acetate at the same level in anaesthetized and awake rats (approximately 4%). Comparing its enrichment with that of blood and liver glucose indicated that brain glucose labelling resulted from hepatic gluconeogenesis. (iii) Analysing glucose 13C-13C coupling in the brain, blood and the liver confirmed that brain glucose could be labelled in the liver through the activities of both pyruvate recycling and gluconeogenesis. (iv) The rate of appearance and the amount of brain glutamate C4-C5 coupling, a marker of pyruvate recycling when starting from [2-13C]acetate, were lower than those of brain glucose labelling from hepatic metabolism. (v) The evaluation of the contributions of glucose and acetate to glutamate metabolism revealed that more than 60% of brain glutamate was synthesized from glucose whereas only 7% was from acetate and that glutamate C4-C5 coupling was mainly due to the metabolism of glucose labelled through hepatic gluconeogenesis. All these results indicate that, under the present conditions, the pyruvate recycling observed through the labelling of brain metabolites mainly originates from peripheral metabolism.

Ex vivo NMR study of lactate metabolism in rat brain under various depressed states.

Brain endogenous lactate metabolism was investigated by ex vivo nuclear magnetic resonance (NMR) spectroscopy study after the infusion of rats with a solution of glucose and lactate labeled as either [3-(13)C]lactate or [1-(13)C]glucose, when their cerebral activity was more or less depressed under the influence of either pentobarbital, alphachloralose, or morphine. We found that: (1) the ratio between the enrichment of alanine C3 and that of glutamate C4, gamma-aminobutyric acid (GABA) C2, glutamine C4, or aspartate C3 decreased from pentobarbital to alphachloralose and morphine whatever the labeled precursor, indicating a link between metabolic and cerebral activity; (2) under glucose + [3-(13)C]lactate infusion, alanine C3 and acetyl-CoA C2 enrichments were higher than that of lactate C3, revealing the occurrence of an isotopic dilution of the brain exogenous lactate (arising from the blood) by lactate from the brain (endogenous lactate), and that the latter was synthesized from glycolysis in a compartment other than neurons; and (3) the contribution of labeled glucose and lactate to acetyl-CoA and amino acid enrichment indicated that the involvement of blood glucose relative to that of blood lactate to brain metabolism was correlated with cerebral activity. The evolution of metabolite enrichments, however, indicated that the cerebral activity-dependent increase in the contribution of blood glucose relative to that of blood lactate to brain metabolism occurred partly via the increase in lactate metabolism generated from astrocytic glycolysis. These findings support the hypothesis for an astrocyte-neuron lactate shuttle component in the coupling mechanism between cerebral activity and energy metabolism.

The lateral supramalleolar flap: experience with 41 flaps.

The lateral supramalleolar flap was used in 41 cases of distal third of the leg, foot, ankle, and heel skin defect reconstruction. The arterial blood supply was mixed in 33 cases and retrograde in 8 cases. The authors recommend raising a distal subcutaneous pedicle to avoid skin grafting over the tendons. In main cases of mixed blood supply, the superficial peroneal nerve could be spared. Eight venous congestions were observed, including 3 with partial flap necrosis. The plastic result was assessed as satisfactory in all but 2 patients. The cosmetic aspect was satisfactory in only 6 patients. Donor site morbidity was minimal, while cosmetic results were assessed as satisfactory in all but 2 patients. The main local alternative was the distally based sural flap, which is technically less demanding. Except for the distal coverage of the foot, indications for both flaps are similar. The distally based sural flap requires the sural nerve to be divided and does not cover as distally as the lateral supramalleolar flap.

Ex vivo analysis of lactate and glucose metabolism in the rat brain under different states of depressed activity.

Brain metabolism of glucose and lactate was analyzed by ex vivo NMR spectroscopy in rats presenting different cerebral activities induced after the administration of pentobarbital, alpha-chloralose, or morphine. The animals were infused with a solution of either [1-(13)C]glucose plus lactate or glucose plus [3-(13)C]lactate for 20 min. Brain metabolite contents and enrichments were determined from analyses of brain tissue perchloric acid extracts according to their post-mortem evolution kinetics. When amino acid enrichments were compared, both the brain metabolic activity and the contribution of blood glucose relative to that of blood lactate to brain metabolism were linked with cerebral activity. The data also indicated the production in the brain of lactate from glycolysis in a compartment other than the neurons, presumably the astrocytes, and its subsequent oxidative metabolism in neurons. Therefore, a brain electrical activity-dependent increase in the relative contribution of blood glucose to brain metabolism occurred via the increase in the metabolism of lactate generated from brain glycolysis at the expense of that of blood lactate. This result strengthens the hypothesis that brain lactate is involved in the coupling between neuronal activation and metabolism.

Low affinity orthophosphate carriers regulate PHO gene expression independently of internal orthophosphate concentration in Saccharomyces cerevisiae.

Phosphate is an essential nutrient that must be taken up from the growth medium through specific transporters. In Saccharomyces cerevisiae, both high and low affinity orthophosphate carriers allow this micro-organism to cope with environmental variations. Intriguingly, in this study we found a tight correlation between selenite resistance and expression of the high affinity orthophosphate carrier Pho84p. Our work further revealed that mutations in the low affinity orthophosphate carrier genes (PHO87, PHO90, and PHO91) cause deregulation of phosphate-repressed genes. Strikingly, the deregulation due to pho87Delta, pho90Delta, or pho91Delta mutations was neither correlated to impaired orthophosphate uptake capacity nor to a decrease of the intracellular orthophosphate or polyphosphate pools, as shown by (31)P NMR spectroscopy. Thus, our data clearly establish that the low affinity orthophosphate carriers affect phosphate regulation independently of intracellular orthophosphate concentration through a new signaling pathway that was found to strictly require the cyclin-dependent kinase inhibitor Pho81p. We propose that phosphate-regulated gene expression is under the control of two different regulatory signals as follows: the sensing of internal orthophosphate by a yet unidentified protein and the sensing of external orthophosphate by low affinity orthophosphate transporters; the former would be required to maintain phosphate homeostasis, and the latter would keep the cell informed on the medium phosphate richness.

Surgical treatment of traumatic lesions of the axillary nerve. A retrospective study of 33 cases.

The purpose of this study was to evaluate the recovery of muscular strength after surgical intervention in axillary nerve injuries. Surgery was elected when no signs of recovery were noted after three months of conservative treatment. Between 1980 and 1996, 46 traumatic lesions of the axillary nerve were surgically treated. Thirteen patients were excluded from the study for various reasons. Among the remaining 33, 20 with interruption of the nerve trunk were treated with nerve grafts and 13 lesions with the nerve in continuity underwent neurolysis. After a mean follow-up of more than two years, deltoid muscle strength was good or fair in 18 patients and poor in 15 cases. The outcome seemed to be better in isolated lesions than in complex nerve lesions with a favourable outcome in 6/10 patients vs 8/14, in patients younger than 25 years compared to older patients (8/14 vs 8/19), in patients treated with neurolysis (9/13) compared to grafting (9/20), and when graft length was limited (4/4 patients with a graft 6cm or less, 5/8 with a graft over 6cm in length). The outcome was less favourable when associated osteoarticular lesions were present (8/23 versus 8/10) and most convincingly, when surgery was delayed beyond six months (10/22 versus 8/11).

Intramuscular innervation of upper-limb skeletal muscles.

We studied 150 skeletal muscles from 8 upper limbs using the modified Sihler's staining technique. Based on the pattern of the intramuscular innervation and shape, the muscles were grouped into trapezoidal-shaped (Class I), spindle-shaped (Class II), and muscles that were combinations of these two classes (Class III). Such distinctions are clinically important for limb reconstruction procedures. Bipennate, spindle-shaped muscles with the aponeurosis of the tendons of insertion extending proximally into the muscle belly and Class III muscles with multiple tendons of origin may be split for separate independent functional transfers.