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The Legal 500 Hall of Fame highlights individuals who have received constant praise by their clients for continued excellence. The Hall of Fame highlights, to clients, the law firm partners who are at the pinnacle of the profession. In Europe, Middle East and Africa, the criteria for entry is to have been recognised by The Legal 500 as one of the elite leading lawyers for seven consecutive years. These partners are highlighted below and throughout the editorial.
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France > Employment > Law firm and leading lawyer rankings
Index of tables
- August Debouzy
- Bredin Prat
Capstan Avocats, member of Ius Laboris
- Chassany Watrelot & Associés (CWA)
- Flichy Grangé Avocats
Fromont Briens
- Proskauer Rose LLP
- Actance
- De Pardieu Brocas Maffei
Freshfields Bruckhaus Deringer LLP
- Gide Loyrette Nouel A.A.R.P.I.
- Jeantet
- Latham & Watkins
- Orrick Rambaud Martel
- Vivant Chiss
Allen & Overy LLP
- AyacheSalama
- BCTG Avocats
- brL Avocats
- Baker McKenzie
- Bird & Bird
- Clifford Chance
- Coblence & Associés
- Cohen & Gresser LLP
- DLA Piper
- Dechert LLP
- Dentons
Dupiré Avocats
- Franklin
Herbert Smith Freehills LLP
- Hogan Lovells (Paris) LLP
KGA Avocats
- LPA-CGR avocats
MGG Legal
Ogletree Deakins
Pech de Laclause Bathmanabane & Associés
- Racine
- Reinhart Marville Torre
- TNDA: Tuffal-Nerson Douarre & Associés
UGGC Avocats
- Vaughan Avocats
Other recommended firms
BMH Avocats
- SCP Bardavid Tourneur
- Bignon Lebray
Brunswick Société d'Avocats
Cornet Vincent Ségurel
- DS Avocats
- De Gaulle Fleurance & Associés
- Delsol Avocats
- Eversheds Sutherland (France) LLP
Fidere Avocats
- Gowling WLG
- Guillemin Flichy
Harlay Avocats
- Jones Day
- M B A - Moisand Boutin & Associés
- McDermott Will & Emery AARPI
- Morgan, Lewis & Bockius LLP
Norma Avocats
Paul Hastings LLP
Reed Smith
Sea Avocats
STC Partners
- Scotto Partners
Simon Associés
- Simmons & Simmons LLP
Skadden, Arps, Slate, Meagher & Flom LLP
- Spring Legal
- Squire Patton Boggs
Stehlin & Associés
- Vivien & Associés
Voltaire Avocats
Wan Avocats
- White & Case LLP
Hall of Fame
Leading individuals
- Emmanuel Bénard - Orrick Rambaud Martel
Guillaume Bordier -
Capstan Avocats, member of Ius Laboris
- Grégory Chastagnol - Fromont Briens
- Nicolas de Sevin - CMS
Pascal Lagoutte -
Capstan Avocats, member of Ius Laboris
- Laurent Marquet de Vasselot - CMS
Jean-Michel Mir -
Capstan Avocats, member of Ius Laboris
- Jean Néret - Jeantet
Gwen Senlanne -
Freshfields Bruckhaus Deringer LLP
Bruno Serizay -
Capstan Avocats, member of Ius Laboris
- Patrick Thiébart - Jeantet
- Antoine Vivant - Vivant Chiss
- Jérôme Watrelot - Chassany Watrelot & Associés (CWA)
Next generation lawyers
- Olivier Angotti - Jeantet
Jean-Martial Buisson -
Fromont Briens
- Aurélie Cormier Le Goff - Flichy Grangé Avocats
- Déborah David - Jeantet
Jean de Calbiac -
Fromont Briens(compensation and benefits)
Guillaume Desmoulin -
Fromont Briens
- Cyril Gaillard - Bredin Prat
- Cédric Jacquelet - Proskauer Rose LLP
- Nicolas Léger - Proskauer Rose LLP
- Cécile Martin - Proskauer Rose LLP
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August Debouzy's highly experienced 26-lawyer team provides 'great expertise' as well as 'practical advice' to many leading French and international groups on their most challenging and large-scale projects such as plant closures, governmental investigations, mass redundancies and litigation and M&A transactions. Accenture, Alstom Power Systems, AstraZeneca, Delphi, Lapeyre and SNCF are clients. Emmanuelle Barbara particularly stands out, while Fabienne Haas, Marie-Hélène Bensadoun, Virginie Devos, Eric Manca, Catherine Le Manchec and Anaïs Qureshi are all highly recommended.
Bredin Prat's 'very highly rated' 17-lawyer team advises leading French and international corporations on the full spectrum of employment matters, stands out for its 'deep knowledge and ability on large and complex M&A deals' and 'provides responsive and pertinent advice in high stress situations'. The firm recently assisted Zodiac Aerospace with its proposed acquisition by Safran and worked on major restructuring and collective redundancy projects. Finally, the practice also deals with highly sensitive collective and individual litigation: it is representing Uber in a high-stakeselisa case questioning the employment status of some drivers. Air Liquide, Bureau Veritas and Coty are clients. Pascale Lagesse heads the practice and Cyril Gaillard is a key name for sensitive litigation, while for M&A matters, Laetitia Tombarello is praised for her 'particular ability to grasp the business imperatives and holistic picture'.
CMS' 68 lawyers advise large French and international corporations on highly sensitive matters including large restructuring projects, top M&A transactions, and challenging collective litigation. It recently assisted Auchan with its reorganisation into one unique brand, represented Footlocker France in a litigation brought before the French Constitutional Supreme Court which led to a landmark decision, and advised France's public-sector employment agency on a major restructuring and collective litigation. Key clients include BOA, Havas and British Airways. Laurent Marquet de Vasselot and Nicolas de Sevin rank among the top experts in France. Ghislain Beaure d'augères, Pierre Bonneau and Caroline Froger-Michon are other key members of the 14-partner practice. Damien Decolasse was promoted to the partnership.
The 'efficient and responsive' Capstan Avocats, member of Ius Laboris brings 'very valuable support' thanks to 'practical and tailored advice' and a 'very strong expertise when dealing with complex matters'. The 200-lawyers boutique - including 52 partners - has offices in Paris, Lille, Lyon, Marseille and Montpellier, and a solid international network. The firm advises many leading CAC 40 and international companies on their most strategic issues including large-scale restructuring projects; the firm has also extensive experience handling mass litigation. More recently, it was also in high demand for advice regarding working hours, digital transition projects and new collaborative work models. Pascal Lagoutte, the 'creative' Bruno Serizay, who 'has in-depth expertise and an agile mind', Jean-Michel Mir and Guillaume Bordier are the key names. Alexandra Lance, Anne Murgier, Anne-Laure Périès, Delphine Stella-Bernad and Marie-Pierre Olive are among the most promising names within the firm's next generation.
Chassany Watrelot & Associés (CWA) fields 41 lawyers spread across three offices in France, but also has additional offices in Morocco, Tunisia and Algeria. The firm is regularly retained by many of France's leading companies and large international groups seeking advice on high-profile restructuring, mass redundancy projects and related litigation. The firm also advises in the context of top M&A transactions and has strong compensation and benefits and social security expertise; it was recently involved in very significant social security contributions reassessments. Highlights included advising Avenir Telecom on its reorganisation plan and Maersk group on various reorganisation projects. Air France, Imperial Tobacco-Seita, Elior and Zimmer Biomet are clients. Philippe Chassany and Jérôme Watrelot co-head the practice. Elisabeth Graujeman, Julien Boucaud-Maitre, Sébastien Poncet and Juliette Pouyet are also key members.
Flichy Grangé Avocats is to be 'recommended without moderation'. The large 70-strong boutique has an 'excellent level of expertise' that is particularly sought after for 'highly technical issues in employment and social security law'. Its lawyers, who are 'available, very responsive and have great listening skills', assist leading French and international corporations, as well as leading international and French corporate law firms, in the context of high-profile M&A transactions and large-scale restructuring projects and regularly manage mass litigation. The practice is representing SNCF before the Court of Appeal in a lawsuit led by some 1,150 Moroccan employees demanding compensation for their differentiated status, and recently obtained a favourable outcome for Charbonnage de France before the industrial tribunal following 755 claims made by former employees regarding safety at work. The team is made up of some 22 partners including top experts Joël Grangé, Arnaud Chaulet, Marine Conche, Florence Aubonnet and Philippe Montanier. Juliana Kovac, Olivier Kress, Nabila Fauché-El Aougri, Stéphanie Dumas, Joumana Frangie-Moukanas, Jeannie Crédoz-Rosier and the 'excellent, very accurate and very business-oriented' Aurélie Cormier Le Goff were also recently involved in key matters. Florence Bacquet, Caroline Scherrmann and Camille Ventejou were promoted to the partnership in 2017 and are all particularly recommended for their advice to international companies.
Lyon and Paris-based and Littler Global's France exclusive member, Fromont Briens 'is a triple-A law firm with a great reputation and a huge number of experts'. The 180-lawyer boutique 'has a very strong practice in any employment law issues' and is 'very much a partner to companies not just an adviser'. The firm represents many leading French and international companies, advising on the market's largest M&A deals and reorganisation projects including mass redundancy schemes, but is equally renowned for its leading social protection, remuneration and professional training expertise. The team shows 'a real in-depth expertise in compensation and benefits', 'is able to take clear positions even on complex questions' and brings 'practical answers and does not try to play it safe'. Key names among the 42 partners include: Gilles Briens, David Calvayrac, Grégory Chastagnol who is 'very sharp and brings a business approach with charm and leadership', Philippe Clément, Cédric Guillon, who is an 'excellent negotiator, very well connected, who gets the job done', Jean-Martial Buisson who 'knows how to explain the pros and cons of optional solutions', Jean-Sébastien Capisano, the 'outstanding' Guillaume Desmoulin who is 'a great leader in international projects' and 'gives efficient and strategic advice', Benjamin Desaint who is 'a very successful expert, great networker, fast thinker who knows how to handle international projects and cross-border cooperation', and Sophie Pelicier-Leovenbruck who is 'highly skilled, a team player, goes to the bottom of things and is a good writer'. Also recently involved in matters were Cécilia Arandel, Julie Béot-Rabiot, Laurence Chrebor, David Blanc, Jean-Jacques Fournier whose 'good overall understanding of the situation and perfect mastery of employment law aspects' are particularly valued, Leslie Nicolaï and Zora Villalard. Of special mention is Jean de Calbiac who stands out for his 'unique expertise combining corporate and employment law' and 'blends technical knowledge, business acumen and the client's context to provide bespoke answers'. Nelly Jean-Marie and Mathieu Hugueville made partner.
The 'highly responsive' Proskauer Rose LLP 'understands multinationals, is extremely creative' and provides 'concrete solutions'. The largest US and European-based corporations, including retail, banking and automobile industry leaders, continually turn to the firm for their most sensitive matters: the 15-lawyer practice recently advised on strategic restructuring, collective disputes, employees transfers and high-profile governance and work council reorganisation issues. The team also has extensive experience in discrimination cases and has strong data privacy and employment expertise. It is also assisting several companies with digital transition projects, notably in the automobile area. Practice head Yasmine Tarasewicz ranks among the leading names in her field and Béatrice Pola is also top notch. The practice also relies on recently promoted partners Cédric Jacquelet and the 'responsive and efficient' Nicolas Léger, as well as international counsel Cécile Martin, who provides 'reliable judgement and finds solutions' and has particular data privacy niche expertise.
Actance's 55-lawyer team advises many listed companies including CAC 40 and SBF 120 companies, as well as high-profile international groups such as Crédit Agricole, Schneider Electric, Public, Kering, Dassault Systèmes, La Poste, BPCE, Henkel and Colgate. The practice advises on restructuring projects and collective agreements and recently assisted Natixis with the negotiation of a group's level one of a kind agreement on mobility, and Suez with a voluntary mass redundancy scheme. The team is made up of nine partners: Franck Blin, Philippe Chapuis, Eliane Chateauvieux, Pierre-Alexis Dumont, Laurent Jammet, Emeric Sorel , Loïc Touranchet, Lucie Vincens and Jean-Michel Renucci. Chloé Bouchez made partner.
De Pardieu Brocas Maffei's nine-lawyer team advises some of France's most emblematic corporations, especially in the engineering, energy and transport sectors, on very challenging and strategic projects, including recent assistance with major restructuring matters. The practice also advises in the context of key M&A transactions. Philippe Rozec is highly recommended and counsel Elise Bénéat is another name to note.
Freshfields Bruckhaus Deringer LLP's 'excellent and responsive' nine-lawyer team provides 'strong, pragmatic and solution-oriented advice' and has particular expertise in high-profile cross-border projects and restructuring work including litigation. Large international groups such as LafargeHolcim, Siemens and Bristol Mayers Squibb are clients. Practice head Gwen Senlanne 'adds value, has clear understanding of the differences between UK and French law, and is practical in achieving commercial goals'. Counsel Christel Cacioppo is 'technically very strong'.
Gide Loyrette Nouel A.A.R.P.I.'s 'always responsive' 23-lawyer team gives 'excellent practical advice' to many French leading companies and some large international groups from various industries, such as the luxury goods, leisure and hospitality, aviation and energy sectors. Recently, the practice has been dealing with highly sensitive restructuring and litigation issues including illicit subcontracting of workers, co-employment, unfair competition, site closure, employees transfers and strikes, but also advised on some large M&A transactions. Air France, EDF, LVMH and Engie are clients. Baudouin de Moucheron jointly heads the practice with Foulques de Rostolan, who 'has longstanding experience and shows personal involvement'. Also highly recommended are Aurélien Boulanger, David Jonin, who designs 'efficient litigation strategies', Guillaume Navarro and François Vergne.
Jeantet shows 'impressive knowledge of employers' obligations and duties' and 'perfect technique'. The 'very responsive' 20-lawyer team provides 'very good legal strategy recommendation' and advises prominent French and international clients on high-stakes matters, notably major work reduction plans, sensitive litigation, negotiation of Sunday and evening work, work accidents and social contribution issues. The firm has particular expertise assisting companies facing insolvency proceedings and assisted Tati with its restructuring. Valeo, Fiat Chrysler Automobiles, Foot Locker and Vallourec are clients. The team is led by Jean Néret, Patrick Thiébart, Déborah David and Olivier Angotti, whose 'high professionalism and listening abilities' are particularly praised.
Latham & Watkins, which shows 'great ability to quickly analyse issues at stake', is entrusted by many leading French corporations, as well as some large international groups and new major client wins to handle high-stakes matters. The 'available and responsive' eight-lawyer team was recently involved in two landmark M&A transactions and has great experience in handling mass litigation. Notably, the practice is defending a bank in a very sensitive case initiated by traders regarding bonuses and is dealing with complex and high-stakes co-employment, international contract status and social security contribution matters. Compliance is another area of expertise. Matthias Rubner, who is in sole charge following Agnès Cloarec-Mérendon retirement, has 'deep and perfect knowledge of the German language and legislation'. Counsel Emily Grimshaw is also involved.
Orrick Rambaud Martel is recommended for managing 'collective or individual employment issues with high social and financial impacts at stake'. The 'highly responsive, efficient and adaptable' 13-lawyer team advises leading French and international corporations and recently handled major restructuring projects, mass litigations, sensitive dismissals of top executives, high-profile M&A and bonus and employment contract requalification issues. Highlights included assisting ThyssenKrupp with the reorganisation of its elevator division in France, and representing Orange in a co-employment litigation case involving around 150 former Teleperformance's employees. Mondelēz, Crédit Agricole, HSBC and Euro Disney are other clients. Practice head Emmanuel Bénard is 'creative, serious and highly competent' and the 'expert' Hélène Daher made partner. Christine Guillot-Bouhours is now at Degroux Brugère.
Vivant Chiss is entrusted by some of France's most prestigious companies such as L'Oreal and Guerlain and deals with highly complex collective issues including large reorganisation projects and job reductions, negotiations of collective agreements and public M&A transactions. The firm notably assisted Vivendi with its amicable take over bid on Havas. Manpower is another key client. Antoine Vivant ranks among the top names in the market and Romain Chiss, Florence Froment-Meurice, Erwan Jaglin as well as Clémence Souchon are also involved.
Allen & Overy LLP's eight-lawyer team advises large French, European and international clients on M&A transactions and the firm has a high-level stand alone practice, handling complex negotiations of collective agreements, exit of high-level executives and management's remuneration packages, as well as social security contribution, restructuring projects and litigation matters. The firm notably assisted Endemol Shine with its acquisition of Shine France. Primark is also a client. Practice head Claire Toumieux enjoys strong recognition and counsel Olivier Picquerey is also involved.
The 'responsive and easy going' Altana advises many leading French and international clients including banking, pharmaceutical, luxury good, retail and industrial and engineering corporations. The eight-lawyer team shows 'excellent expertise and analytical skills', handles both advisory and litigation matters and recently advised on top executive and traders issues, restructuring, collective dismissals, employee transfers and contract requalification matters. The client roster includes Crédit Suisse, Pfizer, Airbus, Hédiard and Limagrain. The team is jointly led by Marianne Franjou, as well as Pierre Lubet and Mickaël d'Allende who both show 'great responsiveness, business acumen and flexibility with a high level of technique'.
The 'extremely responsive' AyacheSalama provides 'high technique and business-oriented advice'. Headed by Caroline André-Hesse, the four-lawyer team assists several leading French corporations such as Lagardère Active with M&A and private equity transactions, complex restructurings, collective litigation and executives' contract terminations. The practice notably advised Advent and Oberthur Technologies on the acquisition of Safran Identity & Security.
BCTG Avocats has a 'great team who is very hands-on and always looks for the best solution'. The six-lawyer practice regularly represents high-profile French, US and Asian corporations in sensitive mass litigation proceedings and advises on co-employment and restructuring issues. Other areas of expertise include outsourcing projects, Sunday work negotiations, asbestos exposure and managers' departures. Practice head Sabine de Paillerets is 'very much involved and wants the best for her clients'.
brL Avocats provides 'high quality work' and its lawyers are 'highly responsive, always practical and come up with creative solutions'. The firm advises some of France's most prominent companies from various industries, including retail and luxury goods, while some leading international corporations also seek out the 37-lawyer boutique for advice on strategic restructuring work and sensitive issues such as Sunday work, litigation and collective negotiations. Expertise also exists in the context of M&A transactions, where the group notably assisted Elsan with the acquisition of MediPole Partenaires. Social security, health and safety and training capabilities are also available. The client roster includes AGCS, Philips Lighting, Vinci and Conforama. Jean d'Aleman, Guillaume Brédon whose 'highly pertinent and practical approach' is greatly appreciated, the 'serious and available' Nicolas Czernichow and Thomas Godey are the key names. Thomas Humbert, Saïd Sadaoui and Véronique Martin-Bozzi are other names to note.
Baker McKenzie stands out for its worldwide expertise that allows the firm to manage global M&A and restructuring projects undertaken by multinationals. The 17-lawyer Paris team is often handling French aspects of global projects and recently dealt with site closures, expatriation and mass redundancies. Many large French and US industrial groups are clients. The team is led by Olivier Vasset, Denise Broussal and Gilles Jolivet.
Bird & Bird has an 'exceptional' team that 'delivers expert and perfectly tailored business advice' with a 'fast turn around'. The 15-lawyer practice particularly assists leading international and French IT, telecoms and pharmaceutical corporations with restructuring and collective employment law issues and recently advised Albany International on collective redundancy issues. SFR-Numericable, Danaher, HanesBrands and Aptalis Pharmaceutical are key clients. The team is co-headed by Alexandra Stocki and Benjamine Fiedler, who provides 'exceptional negotiating skills for high-stakes and critical business initiatives and brings incalculable value to clients' organisations'. Other key names include Nathalie Devernay and counsel Chris Ivey, who 'is truly irreplaceable, detailed and highly precise, yet highly commercially attuned and practical'.
The 'extremely well-connected' Clifford Chance 'goes the extra mile' and is a 'great adviser to succeed in conducting complex reorganisation projects'. The 'always highly responsive' eight-lawyer team provides 'very practical and positively creative advice in complex situations' and assists numerous industrial clients, including several automobile equipment companies, with large and sensitive restructuring projects, including mass redundancies and litigation. The team is notably representing Schaeffler as shareholder of Continental in a groundbreaking case seeking its client's civil liability for the closure of Clairoix's plant and also assisted Fujifilm Holdings France, Fujifilm Medical Systems France and Fujifilm Graphic Systems France with the merger of the three companies. 'Very committed' practice head François Farmine is 'a fantastic professional who provides creative solutions', 'makes his clients' business his own affair' and 'is also a nice person with whom it's nice to work with even for long hours in a stressful context'.
The 'very responsive', 'reliable and trustworthy' Coblence & Associés provides 'tailored, concrete and concise' advice to a loyal client base made up of many audiovisual, media and IT blue-chip French and international clients. The team handles key advisory and litigation work and recently dealt with strategic restructuring and M&A projects. Radio France, PSA, Allianz and Daimler are clients. Headed by the 'highly available' Elisabeth Laherre who has 'exceptional expertise', the 14-lawyer team stands out for its high partner involvement: Chantal Giraud-van Gaver who is the market's reference for assistance to executives, Catherine Davico-Hoarau, Charlotte Hammelrath, Laurent Guardelli and Martine Riou are the names to note.
Cohen & Gresser LLP provides an 'excellent level of service' that demonstrates 'a great understanding of what is at stake for the client', shows 'great business focus' and delivers 'advice that is perfectly adequate and efficient'. The three-lawyer practice advises high-profile French, US and German clients on highly strategic reorganisation and mass redundancy projects, litigation and M&A deals and also has strong expertise in advising companies and top management on mobility, remuneration and termination issues. Bayer SAS and HealthCare and Euro Cargo Rail are key clients, as well as some prestigious brands in the luxury goods sector. Practice head Angéline Duffour impresses with 'great technical knowledge' and 'astute advice'. 'Smart and always available' counsel Anna Milleret-Godet is also one to watch.
DLA Piper provides 'excellent service' and is entrusted by many large Anglophone and UK corporations. The 21-lawyer team deals with sensitive matters including restructurings, plant closures, mass redundancy issues as well as related litigation and also advises in the context of M&A transactions. Adobe, Associated Press, Atmel and easyJet are clients. Practice head Philippe Danesi is 'very available and delivers clear and concise advice to an international audience'. Bijan Eghbal, Marine Gicquel and Jérôme Halphen are the other key members.
Dechert LLP 'is capable of producing advice for an international group in a speedy and comprehensive way'. The eight-lawyer team advises many leading US and international corporations on strategic work including restructuring and post-merger projects, collective litigation, workforce transfers and also has particular harassment and discrimination expertise. Accenture, Kerry, Texas Instrument and Wright Medical are clients. The 'very business driven' Philippe Thomas heads the practice and 'very thorough' associate Sabrina Chekroun 'crafts strategies adapted to clients' needs' and is recommended for 'her strategic vision and high creativity when dealing with complex matters'.
Dentons' 12-lawyer team shows 'great expertise and professionalism' in advising key clients in the banking and financial services, luxury goods, hotel and leisure and healthcare sectors. The practice is involved in some key restructuring, mass redundancy and contract requalification matters. The client roster includes BNP Paribas, Constellation, Plaza Athénée and Warner Chilcott. Katell Déniel Allioux, Frédérique Meslay-Caloni and Julie Caussade head the practice. Aurélie Fournier and senior counsel Jean-Louis Magnier are also involved.
Dupiré Avocats provides 'high added value advice' to leading French corporations, especially in the press and luxury goods sectors, 'fully collaborates with its clients' strategy and is ready to take on measured risks to fulfil it'. The firm was recently involved in strategic restructuring projects and Sunday work negotiations. It assisted Altran with the closing of a subsidiary and the establishment of its European work council. Mondadori France Magazines, Unibail-Rodamco and Libération are clients. Rémi Dupiré, who is 'one of the few experts in French employment press law', 'combines remarkable knowledge with a strong practical sense and deep understanding of the business issues at stake'. Marie-Adelaide Favot is an 'excellent pleading advocate'.
Fidal has one of the market's largest teams with some 300 lawyers involved and stands out for its geographical coverage thanks to 90 regional offices. The group's comprehensive expertise includes labour law, health and safety, retirement and benefits, remuneration and employee savings as well as criminal labour law know-how and support. It advises large French and international corporations as well as SMEs and recently assisted with working time negotiations, religious belief issues, site closures and restructuring projects. Coopérative Lur Berri, Thiriet, Baudelet and Kubota are clients. Stéphane Béal heads the practice. Patricia Blanche-Rotermund, Grégory Olczak-Godefert, Michel Duhaut, Didier Millot, Anna Ferreira and Jean-Marc Chonnier were recently particularly visible.
Fieldfisher's four-lawyer team advises several major international companies as well as some French companies on sensitive restructuring projects, plant closures, as well as remuneration issues and departure of executives. It is advising Caterpillar on the closure of a plant and representing the same client in an equal-pay dispute involving about 700 employees, as well as Molex in a large-scale litigation. Laurence Dumure Lambert 'is expert in her appreciation of French employment law and in providing strategic advice'.
Franklin's well-experienced four-lawyer team is regularly instructed by leading French corporations as well as some large industrial US companies seeking advice on sensitive matters including site closures, restructurings, downsizing and M&A projects. In recent highlights, the practice handled a highly strategic profit-sharing plan dispute. Claire Fougea heads the practice, which also includes of counsel Marion Briere Segala.
Herbert Smith Freehills LLP's 'very good' seven-lawyer team frequently advises a prominent client base of French and international clients on challenging restructuring and litigation matters, but also assists in the context of M&A transactions and has particular expertise in managing multijurisdictional issues. Highlights included assisting UBS France with the acquisition of Banque Leonardo SA, EDF's UK subsidiaries in relation to Hinkley Point C nuclear power station construction project, and Stagecoach with the closure of its business in France. Computer Sciences Corporation and Danone are other notable clients. The highly dynamic Sophie Brézin heads the team and Emma Röhsler 'is very professional, clever, to the point and nice to work with'.
Hogan Lovells (Paris) LLP advises many highly-profile Anglophone clients, as well as some major French corporations, including leading names in the life sciences, luxury goods and financial services sectors. The 14-lawyer team is adept at advising on restructuring, site closure, contract status and mass litigation issues and recently assisted key client MSD with the sale of one of Schering-Plough's industrial sites in France as well as Bpifrance with the setting up of a new employees' collective status scheme. Dominique Mendy heads the practice, which also includes Thierry Meillat and Muriel Pariente.
KGA Avocats' 'practical' team 'puts itself into its clients' shoes and is prompt in giving straight advice'. The practice advises major corporations on strategic issues and also represents executives and several international embassies. It notably deals with high-stakes individual litigation and clients appreciate the team's 'ability to solve issues through negotiation'. Stéphane Bloch, the 'highly available, efficient and accessible' Patrick Berjaud and Michèle Dauvois are in charge.
LPA-CGR avocats advises on employment aspects of M&A transactions and also handles restructuring projects and international mobility matters. The 13-lawyer team assists several large industrial French companies and recently advised Duc on its acquisition by Plukon Food. La Française de l'Energie, Michael Kors and BNP Paribas are clients. Practice co-heads Karine Bézille and Alexandre Bensoussan are recommended, along with Françoise Pelletier.
Linklaters has an 'available, efficient and knowledgeable' practice that delivers 'swift good quality work'. The eight-lawyer team is highly adept at advising on high-profile domestic and cross-border M&A transactions and recently assisted L'Oréal with the sale of The Body Shop International. The practice also handles stand-alone work including mass litigation, restructuring projects and working time disputes. On the contentious front, it represented Exide Technologies in a mass litigation involving 69 former employees following a factory closing. Lionel Vuidard is acknowledged for his 'in-depth expertise, responsiveness and client service'. Counsel Géric Clomes is the other key member of the practice.
MGG Legal's 'technically excellent' 11-lawyer practice is 'very responsive and effective', stands out for its 'thorough analysis' and 'takes clear positions'; the group also provides 'service in English that is relevant, appropriate and very carefully and delicately prepared to support clients'. The firm has a large international client base while also advising some key French companies on a wide range of strategic topics, including Sunday work, employee transfers, closing down of operations, reorganisations, individual and mass litigation, protected employees' termination, and M&A deals. It recently represented Mariage Frères in Sunday work litigation. Marijke Granier-Guillemarre is 'reliable and answers quickly' and Loïc Héron is 'extremely congenial, has excellent knowledge and a good and commanding presence to represent clients in meetings'. Sébastien Le Coeur made partner.
US firm Ogletree Deakins opened its Paris office in March 2017, thus becoming the first international employment-focused firm to set foot in France. The eight-lawyer Paris practice assists many leading international corporations, including some leading internet players, as well as some major French groups with strategic issues and is involved in several high-stakes litigation concerning incentive schemes and the definition of work contracts. The team also advises in the context of restructuring and M&A projects. Karine Audouze, who joined from Olswang Paris after its closure, is 'very able and experienced'. Jean-Marc Albiol, who previously spent most of his career at Hogan Lovells (Paris) LLP, is 'always pro-active and business-oriented, provides an approach to complicated matters that is always practical' and 'takes excellent care of a diversified French and international client base'.
Pech de Laclause Bathmanabane & Associés' 'responsive, available, efficient and precise' six-lawyer team advises leading French corporations, especially leading engineering groups, on complex restructuring projects, strikes, social security investigations and is notably involved in a very sensitive illegal employment case. Jean-François Tréton and Pascal Bathmanabane, whose 'quality of judgment and diagnostics of the situation are very valuable', are the key contacts.
Racine's 'highly performing' 32-lawyer team, which is based in Paris and in the regions, demonstrates a 'high level of service' and 'strong knowledge of the law'. The practice is especially recommended for complex matters such as managers' remuneration and employees' incentives issues and also has particular expertise in advising distressed companies facing insolvency proceedings: it notably represented Isochem during its difficulties and potential sale. In other work, the group is handling a sensitive mass litigation concerning temporary work payment contributions and advised on a site closure. It also assisted Mediawan with its acquisition of Groupe AB. Finally, the team is often retained by high-level executives. The practice is jointly led by the 'practical' Frédéric Broud who shows 'great ability to understand clients' needs and expectations', Sarah Usunier, Carla Di Fazio Perrin and Alain Ménard.
Raphaël's 'available and experienced' ten-lawyer team 'remains extremely close to its clients, is able to comfortably work in English and with foreign law firms' and provides 'qualitative services'. Leading French banks notably turn to the firm for strategic matters including restructuring projects and high-level executive terminations. Recent highlights include assisting BNP Paribas Personal Finance with the absorption and merger of several of Laser's subsidiaries, as well as Gefco with a unit reorganisation. CACIB, Société Générale and BETC are key clients. The practice is jointly headed by Isabelle Ayache-Revah and Marion Ayadi, who both 'give high level analysis and provide key support in making important decisions', as well as the 'practical and available' Philippe Rogez.
Reinhart Marville Torre's 'professional, available and responsive' ten-lawyer practice frequently assists large French and international companies such as L'Oréal, Siemens, ThyssenKrupp and AEG as well as some SMEs and non-profit organisations with challenging individual litigation, working time issues, co-employment disputes and restructuring projects. It recently advised non-profit entity Coallia on the termination of its activity. The 'extremely able, precise and available' Catherine Broussot-Morin and Soazig Preteseille, who is praised for her 'professional and interpersonal skills', are the key contacts. Olivier Bluche is a go-to-lawyer for high-profile CEO termination issues and recently assisted Eramet with the termination of its former CEO. Agathe Moreau is highly experienced in dealing with work accidents and related illnesses, gross negligence and criminal liability matters.
TNDA: Tuffal-Nerson Douarre & Associés' 12-lawyer team stands out for 'its very hands-on approach, proven expertise and true understanding of the human dimension at stake in a file', 'is convincing during negotiations' and provides 'tailored advice that unlocks situations'. The group advises many leading French and international corporations as well as banks and associations on sensitive and high-stakes employment issues and recently assisted with the restructuring of a company placed under safeguard proceedings. Health and criminal employment law issues are also dealt with. Of counsel Martine Rivereau-Trzmiel who 'is highly involved in matters and provides a great tactical approach and support from the beginning to the end', the 'greatly available and excellent negotiator' Nicolas Durand-Gasselin, Guillaume Verdier, who provides 'strong support' and 'clear issues analysis', and Véronique Tuffal-Nerson are highly regarded. Also recommended for their complementary expertise are criminal partner Rémy Douarre, whose 'fine analysis, acute and vast knowledge and excellent advice' are particularly appreciated, as well as Philippe Meylan and of counsel Armelle Walters-Renaud for corporate support.
UGGC Avocats' ten-lawyer team assists several leading French and international corporations with restructuring projects, litigation and employment aspects of M&A transactions. The practice is led by Sophie Uettwiller and the 'knowledgeable, concise and straight to the point' Jennifer Carrel.
Vaughan Avocats advises many large French and international corporations on key matters including high-profile M&A transactions as well as site closure and mass redundancy plans. The 30-lawyer practice also provides 'very professional and efficient services' and 'concrete and tailored advice' on international mobility issues. The team recently assisted De Sangosse with a redundancy plan. Key names among the ten-partner practice include Bruno Courtine, Jean-Charles de Bellefon, Bastien Ottaviani - Thomas Fernandez-Boni and the 'responsive and practical' Sandra Thiry.


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Week 26 | New City Catechism and Scripture
Every week, our worship bulletin includes a QA from the New City Catechism, along with a supporting Bible verse that we invite you to memorize. This week's QA, memory verse, and explanatory video are below: New City Catechism #26 Q. What else does Christ's death redeem? A.Christ's death is the beginning of the redemption and renewal of every part of fallen creation, as ...Keep Reading

subset: commoncrawl


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Made in the UK
Especially for our 2nd Birthday we have commissioned a stunning burgundy edition of one of our best selling products. An absolute essential item for anyone who has a connection to Ilkley!
Such a simple yet effective print of a vintage map of Ilkley nestling within a literal 'Cow & Calf'.
For postal orders we provide the prints mounted but UNFRAMED. (Mounted print measures 29.5cm x 21cm)
For those wishing to 'click and collect' the prints can be purchased double mounted and framed in a choice of a black or oak(42.5cm x 32.5 cm)


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Buyers for the Federal Government access certain benefits upon registering for an account.
With over 15,000 items on our three contracts, there isn't much QuickMedical can't offer. Browse below, or call us at 1.888.345.4858, and we'll be happy to help!
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QuickMedical has access to over a thousand items on a GPO contract through dozens of distributors and two GPOs. Browse below, or call us at 1.888.345.4858!
Eligible customers can upload POs and pay with Net-30 Terms online! Click below to apply today.
QuickMedical offers a variety of Anatomical OB/GYN Charts for educational purposes. Great for classrooms, family planning centers, and medical facilities, anatomical charts help teachers and physicians expain anatomy and physiology to patients and students. OB/GYN Charts offer educational resources for birth control, pregnancy, childbirth, female anatomy, and more.


text: Valencia CF come back from behind with spirit (2-1) January, 17 2018 - The goals from Guedes and Rodrigo turned it around and the tie will be decided at Mendizorrotza Valencia CF were back in action in the Copa del Rey quarter-finals first leg against Club Deportivo Alavés on Wednesday evening at Mestalla at 7 pm kick-off time. Marcelino's side were looking to put the knock-out tie on the right track ahead of the second leg at Mendizorrotza. Valencia CF were off to a slow start, they were pushed on the back foot by the opposition in the opening minutes of the first half while Marcelino's side were trying to play their typical possession football. The first Valencia CF chance fell to Guedes following a great link-up play with Simone Zaza and the Portuguese's shot whistled wide off the target. Marcelino's side grew into the game so much so, that a minute later, Kondogbia tested Antonio Sivera from 25 yards out which was pushed away by the keeper. Gonçalo Guedes came close to scoring following a delightful combination with Parejo who played a line-breaking pass into Guedes which dragged his effort a whisker wide of the post over the quarter-hour mark into the first half. The tempo of the game increased halfway through the first half with both sides exchanging chances at both ends. The opposition forced Jaume into a save over the 30-minute mark, Jaume saved Hernán Pérez shot at his near post. Four minutes later, Guidetti tried his luck from a set-piece but Jaume pulled off a smart stop. The first half finished goalless with nothing to separate the sides and all to play for in the second half. Marcelino's side came out in the second half looking to break the deadlock and get the win to take a positive step forward in the tie, so much so that he introduced Rodrigo Moreno five minutes into the second half. Valencia CF forward Luciano Vietto enjoyed the first Valencia CF chance in the second half. CD Alavés broke the deadlock against the run of play through Sobrino with a right-footed shot from outside the area into the top left corner beyond Jaume. Valencia CF struck back with a delightful Guedes equaliser with just over twenty minutes of normal time left to play. Guedes pounced on a Sivera error who spilt the ball for the Portuguese to slot it home. CD Alavés were reduced to ten men when Adrián Diéguez got dismissed for a double booking for a foul on the aforementioned Gonçalo Guedes. Valencia CF made their numerical advantage pay with 82 minutes on the clock. Rodrigo drilled home from inside the box following a great Santi Mina pass which Rodrigo netted in off the post. The scoreline remained unchanged and Valencia CF managed to put the tie on the right track coming from behind in a thrilling first leg which they will have to seal next Wednesday at Mendizorrotza same kick-off time. Match details: 2. Valencia CF: Jaume, Montoya, Garay, G. Paulista, Gayà, Parejo, Kondogbia, Andreas (Rodrigo, m. 57), Guedes, Vietto (Santi Mina, m. 70) and Zaza. 1. Deportivo Alavés: Sivera, Martín, Alexis, Maripan, Diéguez, Dani Torres, T. Pina, Hernán Pérez (Ibai, m. 76), Wakaso (Pedraza, m. 67), R. Sobrino and Guidetti (Munir, m. 62). Goals: 0-1. M. 66: R. Sobrino. 1-1. M. 73: Guedes. 2-1. M. 82: Rodrigo. Referee: González González, booked Guedes, Santi Mina and Kondogbia for Valencia CF, y a Tomás Pina, Wakaso and dismissed Adrián Diéguez for a double booking on 77 minutes for CD Alavés Observations: First leg of the Copa del Rey quarter-finals which took place at Mestalla at 7pm kick-off time in front of 31,338 spectators. Copyright 2013-2018 Valencia Club De Fútbol. Quoting text from this article is permitted provided that en.valenciacf.com is credited as source, with a clickable link. Photographs by Lázaro de la Peña, re-use is not permitted.


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View of the Garden of Prince Ludovisi
Giovanni Battista Falda, Italian, 1643-1678
View of the Garden of Prince Ludovisi
First published 1677, MCCM edition published ca. 1688
8 15/16 x 16 9/16 in. (22.7 x 42 cm)
Object Number
When his uncle became Pope Gregory XV (1621-1623), Ludovico Ludovisi was made a cardinal and, as befitted a cardinal nephew, began to purchase land for a villa and to acquire antiquities, buying up two celebrated collections that had been put together in the sixteenth century. Since his property, which lay in the valley between the Pincian and Quirinal Hills, was the site of the ancient Gardens of Sallust, he had the good fortune to uncover many buried antique masterpieces on his own land. Several of the statues were displayed in a wooded labyrinth opposite the casino at the lower right. Just beyond this labyrinth in an uncultivated field, Falda has depicted an Egyptian obelisk lying on its side, another relic of the ancient gardens which was not re-erected until 1789. Today the cross-shaped casino at the left is the only remnant of the cardinal's gardens. It contains the magnificent ceiling fresco of Aurora that Cardinal Ludovisi commissioned from the Bolognese painter Guercino in 1621.
margin: VEDVTA DEL GIARDINO DELL'ECCELLENTIS.(MO) SIGNOR PRENCIPE LVDOVISI a Porte Pinciana; below is seven item legend; BL: Falda's name; BR: G.G. De Rossi's address and privilege
The Gardens of Rome (Li giardini di Roma)
Credit Line
Art History Department Fund
Gardens of Rome, Michael C. Carlos Museum, February 14 - May 17, 1998|
Discovering Rome: Maps and Monuments of the Eternal City, Michael C. Carlos Museum, September 16, 2006 - January 14, 2007|
Antichità, Teatro, Magnificenza: Renaissance and Baroque Images of Rome, Michael C. Carlos Museum, August 24 - November 17, 2013
Discovering Rome: Maps and Monuments of the Eternal City, Michael C. Carlos Museum, September 16, 2006 - January 14, 2007|
Antichità, Teatro, Magnificenza: Renaissance and Baroque Images of Rome, Michael C. Carlos Museum, August 24 - November 17, 2013
Antichita, Teatro, Magnificenza: Renaissance & Baroque Images of Rome (Atlanta: Michael C. Carlos Museum, 2013), 58 (checklist only).
© Michael C. Carlos Museum, Emory University. Photo by Bruce M. White, 2008.
This image is provided by the Michael C. Carlos Museum of Emory University, who retains all rights in it. This image is made available for limited non-commercial, educational, and personal use only, or for fair use as defined by United States law. For all other uses, please contact the Michael C. Carlos Museum Office of Collections Services at +1(404) 727-4282 or firstname.lastname@example.com. Users must cite the author and source of the image as they would material from any printed work, but not in any way that implies endorsement of the user or the user's use of the image. Users may not remove any copyright, trademark, or other proprietary notices, including without limitation attribution information, credits, and copyright notices that have been placed on or near the image by the Museum. The Museum assumes no responsibility for royalties or fees claimed by the artist or third parties. The User agrees to indemnify and hold harmless Emory University, its Michael C. Carlos Museum, its agents, employees, faculty members, students and trustees from and against any and all claims, losses, actions, damages, expenses, and all other liabilities, including but not limited to attorney's fees, directly or indirectly arising out of or resulting from its use of photographic images for which permission is granted hereunder.
On View
Giovanni Battista Falda, Italian, 1643-1678, "View of the Garden of Prince Ludovisi," Michael C. Carlos Museum Collections Online, accessed February 19, 2019, http://carlos.digitalscholarship.emory.edu/items/show/8037.
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Everybody feels a little lost after completing their engineering degree. Whether it is Computer Science or Mechanical, there are very few people who actually pick their favorite field fāor getting an engineering degree. Rest assured, engineering is a field in which all the fields are interlinked. From Bosch careers to Siemens careers, there's no dearth of high profile jobs. Therefore, even if you have completed your engineering degree and are figuring out how to choose a job in engineering, then this is for you. Here are some tips on how to choose the right engineering job:
- Research on All Possible Jobs: When you are just out of your degree, you have the slightest idea about your core branch only. You might not be aware of the opportunities in other branches. Therefore, you should research about all possible jobs after engineering and gather whatever information you can get.
- List All Core and Non-Core Jobs That You Are Interested In: There can be many. It is not compulsory that you need one in each category. It is possible that you don't get any core jobs in which you are interested in. Many people shift their career paths after completing their degree. Just make a list and then move on to the next step.
- Make a Checklist of Pros and Cons of Each Job and Shortlist Accordingly: Once you have made the list, you need to categorize your jobs in terms of pros and cons priority wise. The jobs, which have fewer cons according to you and lies higher on the priority list, go into the next round.
- Further Shortlist by Trying Short Projects on Your Own: Each and every job has some sort of introductory project available online. You can take up these projects and get the feel of what lies ahead in that particular job. Once you have gained this experience, you would be able to shortlist your desirable jobs further. It is also possible that you get your dream job in this step.
- Try Live Internships and Trainings in the Shortlisted Jobs: You only know your passion for sure after you have tried it in the industry. There are many trainings and internships available in the industry and these would give you hands-on experience on the jobs you have shortlisted.
- If There Are Still Some Jobs Left, You Know That You Can Excel in Any of These and You Would Enjoy Them Too: Therefore, pick any one job from the list and keep the rest of the jobs when we want to switch our careers later.
There are countless engineering jobs available and picking one can be a daunting task. If you follow these steps carefully, you would get to your dream job in no time.


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Combining coffee time and Show and Tell at the beginning of our gatherings is supposed to help us get into the work room more quickly. But sometimes there is so much to go gaa gaa over!!Kate has had a very productive couple of weeks......this small center piece was a study from a dye workshop she attended. Her beautiful and thoughtful machine quilting turned it into a real piece of art. I love how elevated the look became by mounting it on a chiffon covered canvas.
AND WOW....so clever.....I'd given her this piece of fabric which I'd created using molding paste designs. Having zero idea what I could do with them.....Kate found a way by using it as a backing.
She dug out some of her marbled fabrics made at a Fiber Junkies retreat several years ago. Again, Kate's skill with free motion quilting brought the pieces to life. Though the picture doesn't show it.....she added beads to the top one which added so much motion to the work.
Denny continues creating huge Gypsy Wife quilts....which utilizes UFO blocks and scraps. It's even more colorful and interesting in person than what I could depict in this photo.
She also brought a pile of dyed fabrics for us to gush over. These started out with what she calls clown fabric.....previously dyed/painted etc. fabrics that were disappointments. Over-dyeing with indigo gave her these beauties!
I hosted quilting cruises and tours for over 10 years. For each trip I created 3-d embellished pins for the participants. One year our trip fell over Halloween.....so everyone got two pins....one theme based on our destination and the other one was a Halloween pin. I had access to everyone's room numbers......so while all the quilters were in their cabins dressing for dinner......I donned my Halloween costume and went trick or treating...passing out candy and a pin to each. I came across a few leftover pins the other day and had just enough for each FJ.
Gen had this lap quilt on her wall...it was one of the many our other group - PTA Fiber Artists worked on at our last meeting. Several members like Gen, brought kits home to make additional ones.
Gen never fails to amaze me.....honestly I swear she can make her sewing machine stand up, walk across the room, and take a bow....that is how skilled she is with the sewing machine. Isn't this smashing??
Stay tuned......next up we look at our gelli plate designs.


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This week we will focus on helping you find the perfect stick. For part I we'll be discussing hockey stick flex and how it affects your shots. Part II we will provide guidelines for choosing the right length for your stick, and part III will cover all the different blade types and the impact they have on shooting, passing, and handling. Of course the best way to find the right stick is by experimenting. I strongly encourage you find a teammate about the same size and borrow his stick and see what works best for you!
Hockey stick flex is one of the most important, if not the most important element you should consider when choosing a stick. Can you think of other sports where flex makes a difference? The first two I thought of were archery and pole vaulting. Let's examine the former. The goal of the archer is to shoot the arrow as far and as accurate as possible so he wants to select a bow that will help him do those things. If the bow is too hard for him to pull, the arrow, the string won't be pulled back far enough, and the arrow probably won't make it very far. Conversely, if the string of the bow is too flimsy, there won't be enough tension on the line, and the arrow will fall short of its target. What does this have to do with hockey? A stick works in a similar fashion. If a shot is taken properly, the stick will actually bend like a bow or pole-vaulting stick, then spring back into its original form and in the process, launch the puck forward. Although the video below describes the flex effect in the context of a slapshot, the same principle can be applied to just about any shot.
When purchasing a stick, flex will be given as a number usually from around 60 to 100. In case you're curious the number represents how much force (in pounds) is required to bend the stick 1″. So, the higher the number, the stiffer the stick. A player who is taller and heavier will obviously have an easier time bending the shaft than his shorter, lighter teammate. Therefore, he should choose a stick accordingly. A player ought to look for the stiffest stick he is strong enough to bend. Think back to our archery example: The archer wants to find the strongest bow he is physically capable of pulling.
As a general rule, players are encouraged to find a stick flex with a number equivalent to half their weight. This recommendation, however, does not take height into account. Below is a chart providing guidelines on what stick flex you should choose based on height and weight. Of course there are 6'4″ players who use an 85 flex; this is just a place to start, it is not the final authority on stick selection.
|Under 5′
|Under 130
|Under 50 flex
|80-95 flex
|50-65 flex
|95+ flex
|65-80 flex
Finally, it is important to note that modifying the length of your stick will modify the flex. Below is a chart providing estimates for how stiffness changes when a stick is cut.
|Original Flex
|Flex After Cutting Shorter
|49 flex
|57 flex
|67 flex
|60 flex
|68 flex
|77 flex
|74 flex
|80 flex
|87 flex
|84 flex
|92 flex
|100 flex
|96 flex
|105 flex
|112 flex
|108 flex
|115 flex
|122 flex
Source: HockeyMonkey via Hockey Stick Expert
Coming up next: Hockey stick length
Tags: stick


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Whenever I visit bigger city, I want to bring back something as a present or a reminder of the trip…. But later, I realize that it's almost impossible to find a nice souvenir that has the spirit of the city. Of course, searching for a present is even more stressful. Souvenirs can be quite expensive, yet they often look cheap and end up being poor quality. The fact that souvenirs tend to be overpriced makes this task very difficult. Surprisingly, shops with nicely designed souvenirs do exist. In Prague, one of these special places is called Pragtique. Pragtique sells souvenirs that are a unique reminder of Prague. Each Pragtique item tells a story about Prague with flair and ease, and not only tourists shop here. Pragtique supports everything local, so it's not unusual to find ware by Daniela Olejníková, Tomski&Polanski, Vendula Chalánková and more…
For the 260-year anniversary of the birth of Mozart, Vendula Chalánková and Ondřej Horák made an amazing Prague guidebook called W. A. Mozart in Prague. Vendula Chalánková created a complete set of drawings for this topic, in addition to the book illustrations.
The name of the shop alone, Pragtique, describes its uniqueness. The space is also very quiet, minimalist and welcoming. The whole concept of the shop is marvelous and special to Prague. The store is located in the Platýz Passage, which is close to city centre. In other words, there is no reason not to visit Pragtique while roaming the streets of Prague.
By: Alice Muziková | Edit: Bridget Keane | Photo: Magdalena Šmídová, Yasmin Keshmiri Hejduk


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Nivolumab induced encephalopathy in a man with metastatic renal cell cancer: a case report
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- Citations
Great progress has recently been made in the treatment of metastatic renal cell carcinoma, including the introduction of nivolumab, an immune checkpoint inhibitor. Despite promising results, this treatment brings a completely new spectrum of adverse events, distinct from those experienced with small-molecule kinase inhibitors. Neurologic immune-related adverse events may be serious and potentially life-threatening complications requiring immediate immunosuppressive therapy. Only a few cases of immune-related encephalitis induced by checkpoint inhibitors have been described and the data regarding the management of this serious adverse event are limited.
Case presentation
We report the case of a 63-year-old white man with metastatic renal cancer who developed severe chorea-like dyskinesia during nivolumab therapy. The findings on brain magnetic resonance imaging and flow cytometry of cerebrospinal fluid, and the positivity of anti-paraneoplastic antigen Ma2 immunoglobuline G class autoantibodies were consistent with a diagnosis of immune-related encephalitis. High-dose intravenous corticosteroid therapy was started immediately, with no signs of improvement, even when infliximab was added. Our patient refused further hospitalization and was discharged. Three weeks later, he presented with signs of severe urosepsis. Despite intensive treatment, he died 4 days after admission.
The management of less frequent immune-related adverse events has not been fully established and more information is required to provide uniform recommendations. Immune-related encephalitis is a severe and potentially fatal complication requiring immediate hospital admission and extensive immunosuppressive therapy. The examination of cerebrospinal fluid for paraneoplastic antibodies, such as anti-N-methyl-D-aspartate receptor and anti-Ma2 antibodies, in order to distinguish autoimmune etiology from other possible causes is essential and highly recommended.
KeywordsRenal cancer Nivolumab Encephalitis Immune-related adverse event Case report
- anti-PNMA2
Anti-paraneoplastic antigen Ma2
Twice a day
Central nervous system
Cerebrospinal fluid
Computed tomography
Cytotoxic T-lymphocyte antigen-4
- Ig
- irAE
Immune-related adverse event
- mRCC
Metastatic renal cell carcinoma
Magnetic resonance imaging
- mTOR
Mammalian target of rapamycin
Programmed cell death-1
Programmed death-ligand 1
Renal cell carcinoma
Vascular endothelial growth factor
Great progress has recently been made in the treatment of metastatic renal cell carcinoma (mRCC). Currently available drugs include multikinase vascular endothelial growth factor (VEGF) inhibitors (sunitinib, sorafenib, pazopanib), cytokines (interferon α), and mammalian target of rapamycin (mTOR) inhibitors (temsirolimus, everolimus), with the recent additions of the MEK inhibitor cabozantinib and the immune checkpoint inhibitor nivolumab. Nivolumab is a fully human immunoglobuline (Ig) G4 antibody targeting programmed cell death-1 (PD-1) receptor, which achieves a durable objective response in many cancers including mRCC [1]. Nivolumab acts as a checkpoint inhibitor, preventing the PD-1 mediated transmission of inhibitory signals that would normally attenuate T cell activity. This consequently enables the immune system to regain or maintain its antitumor activity. The anti-PD-1 effect is achieved mainly in tumor tissue during the effector phase of the immune response. Nivolumab is administered intravenously at a dose of 3 mg/kg every 14 days.
The advent of immunotherapy with checkpoint inhibitors has resulted in a completely different spectrum of activity than that experienced with chemotherapy and small-molecule kinase inhibitors. Desired antitumor activity can be achieved in a considerable number of patients. However, stimulation of the immune system response may simultaneously induce symptoms resembling an autoimmune disorder. These adverse reactions are usually referred to as an immune-related adverse event (irAE) and may affect practically any organ or tissue in the human body. Although these adverse reactions are usually mild and easily manageable with appropriate treatment, severe complications with potentially fatal consequences may occur.
We report a case of a patient with mRCC who developed severe chorea-like dyskinesia during therapy with nivolumab. The aim of this case report was to present a rare neurological complication of nivolumab treatment and to emphasize the necessity of close collaboration among the physician, the patient, and the patient's family as a prerequisite for a good clinical outcome.
Case presentation
After finishing radiotherapy, nivolumab therapy was started in May 2016 within an expanded access program at an absolute dose of 300 mg every 14 days. Both diarrhea and back pain were gradually resolving during treatment, enabling dose reduction of the opiates. Our patient completed a total of six doses of nivolumab with no laboratory or clinical signs of adverse effects.
However, 14 days following the last dose of nivolumab, he reported a change in behavior and a history of uncontrollable movements. His family started to say that he was strange and restless. He personally felt very well when taking nivolumab and the pain was even improving. He was fully aware of the uncontrollable movements, and although he could think rationally, he was not able to influence or stop them.
There was no family history of neurological or mental illness, and he denied any head trauma or neurological disorders in the past. A physical neurological examination revealed no significant findings in his head and peripheral nerves, but there were mild generalized choreatic movements of his upper extremities and head. A psychiatrist described our patient as cooperative, with pronounced choreatic movements of the entire body. His behavior was described as social, without signs of hostility or aggression, and at a reasonable psychomotor tempo. His mood was described as mildly dysphoric in response to the current situation of somatic manifestations. Laboratory tests showed no marked abnormalities. The only medication he was on at that time was a transdermal fentanyl patch (100 mcg/hour changed every 3 days), and he intermittently used antidiarrheal medications (diphenoxylate hydrochloride 2.5 mg or probiotics based on Lactobacillus acidophilus metabolites); during the sunitinib treatment, he irregularly used metoclopramide 10 mg, but he denied any history of neuroleptic use. Because of a serious suspicion of a possible side effect associated with immunotherapy, he was admitted to our hospital on 11 August 2016. A general overview of the timeline of the case report is shown in an additional file (see Additional file 1).
According to the recommendations for the management of irAE, high-dose intravenously administered corticosteroid therapy was started: Solu-Medrol (methylprednisolone) 2 mg/kg per day. Trimethoprim/sulfamethoxazole was administered simultaneously to prevent possible infectious complications: 960 mg twice a day (BID) twice a week. Despite the high dose of intravenously administered corticosteroid therapy, there was further deterioration of choreiform movements. The choreiform, athetoid, and ballistic movements spread to his lower limbs and trunk. The choreiform movements were so intense that our patient was unable to rest or lie on a bed. Furthermore, he developed a paranoid hallucinatory syndrome with suicidal thoughts. He was started on antipsychotic therapy (clonazepam 2 mg per day, haloperidol 15 mg per day, olanzapine 20 mg per day) after consultation with a psychiatrist and a neurologist and he experienced partial improvement. Considering the lack of a significant effect of corticosteroid therapy, the administration of infliximab at a dose of 5 mg/kg was started. However, infliximab did not achieve any clinical effect.
Our patient and his family insisted on discharge from our hospital. According to the conclusion of a psychiatric examination, he was pronounced capable of signing an against-medical-advice discharge form and was discharged on 23 August 2016. An early out-patient visit to administer a further dose of infliximab was scheduled, and he was duly informed about the importance of doing so. However, he did not come to visit and refused any further treatment despite the provided information about possible adverse consequences.
He was eventually admitted to the standard ward on 13 September 2016, presenting with a fever and soporific state (Glasgow Coma Scale 5) on admission. Because of urinary retention (initially 1000 ml) and elevated levels of C-reactive protein, we suspected urinary infection, and he was started on intravenously administered amoxicillin/clavulanic acid 3.6 g/day and intravenously administered hydration. No other laboratory abnormalities were found. He partially regained consciousness after 2 days of treatment, with clinical manifestations of aggression and choreiform movement as described above. Therefore, therapy with antipsychotics and corticosteroids was reintroduced. However, his condition started to deteriorate again, and he developed bronchopneumonia. His level of consciousness started to deteriorate again, and he died 4 days following admission.
Immunotherapy is a treatment modality that has experienced a renaissance in the treatment of solid tumors during the last decade. Despite numerous attempts to utilize the immune system to fight cancer, including the depletion of T-regulatory lymphocytes [2], and the use of cancer vaccines or cytokines [3], previous results have been unsatisfactory. However, the discovery and understanding of the function and regulatory role of several receptors and their ligands, that is, cytotoxic T-lymphocyte antigen-4 (CTLA-4), PD-1, and programmed death-ligand 1 (PD-L1) in T cell activation have encouraged the further development and clinical use of immunotherapy [4, 5]. Currently, we can affect these regulatory mechanisms with a new class of drugs called immune checkpoint inhibitors. There is a growing body of evidence that these drugs represent effective treatments with the possibility of achieving a durable response in a wide spectrum of solid tumors, including melanoma [6, 7], non-small cell lung cancer [8, 9], urothelial carcinoma [10, 11], and renal cell carcinoma (RCC) [1].
The pathogenesis of irAEs is closely related to immune regulation affecting the activity of cytotoxic T cells. The mechanism of action of checkpoint inhibitors is to disrupt an interaction between regulatory receptors and their ligands, which normally produce an inhibitory signal with subsequent attenuation of immune activity. If the binding of ligands to regulatory receptors is prevented, for example, by anti-PD-L1 or anti-PD-1 antibodies, the activated T cells can contribute to an antitumor response [12, 13, 14]. On the other hand, this leads to an imbalance and possible disruption of immunological tolerance, which might cause an uncontrolled immune response directed against self-tissue antigens. This may result in undesired inflammatory activity involving various organ systems, referred to as irAEs. The most commonly affected sites are the gastrointestinal tract, skin, and endocrine system, but any organ or system of the human body can be affected.
In our case the initial presentation of adverse symptoms related to nivolumab was poor but unusual with severe chorea-like dyskinesia symptoms. There is only sparse information in the literature about similar cases; that is why the diagnostic and therapeutic algorithm is more difficult than, for example, for immune-related pneumonitis. Our case shows and emphasizes the urgent need of up front resolute immunosuppressive therapy in cases of immune-related encephalitis. Based on our case we propose the paraneoplastic antigen Ma2 as a helpful biomarker in order to make a correct diagnosis and to distinguish immune-related encephalitis from other possible causes.
According to the literature, irAEs affecting the central nervous system (CNS) induced by anti-PD-1 antibody treatment are rare [15]. The vast majority of observed irAEs affecting the CNS have been related to anti-CTLA-4 antibodies [16, 17]. Most cases of immune checkpoint inhibitor-related CNS toxicities were of lower grade, with only approximately 0.1–3% of all events being grade 3 or 4 [18]. There are a limited number of anecdotal reports regarding anti-PD-1 antibody-induced autoimmune CNS toxicities [19, 20, 21].
Immune-mediated encephalitis can be difficult to distinguish from encephalitis related to other causes. It can produce a wide range of symptoms, including headache, fever, weakness, fatigue, impaired memory, hallucinations, and convulsions. The diagnosis is usually made per exclusionem (a diagnosis of exclusion). Immune-mediated encephalitis induced by checkpoint inhibitors usually arises at the very beginning of therapy [15, 19]. However, as we demonstrate here, it can occur at any time during therapy.
The ratio of CD4+/CD8+ T cells in aseptic meningitis is typically approximately 3:1 [22]; however, it was unusually low in our case (approximately 1:1). This result is probably because the PD-1 receptor is strongly expressed on CD8+ T cells [23], resulting in the proliferation of the CD8+ subpopulation. Another explanation is that the CD4+/CD8+ ratio naturally decreases during inflammation, so the result might be affected by the time of examination [24].
The exact mechanism of immune-mediated encephalitis remains unclear. It is believed that the majority of irAEs are caused predominantly by T cells, although some proportion of irAEs may be mediated by other immune cells. N-methyl-D-aspartate (NMDA) receptor antibodies seem to play an important role in the pathogenesis of immune-mediated encephalitis [25]. These antibodies have been found in patients who developed immune-mediated encephalitis related to immune checkpoint inhibitor therapy [19]. NMDA receptors are expressed on the surface of melanocytes and are coded by the gene GRIN2A, which tends to be highly mutated in patients with melanoma [26]. The formation of antibodies against aberrant NMDA receptors in melanoma is supposed to induce encephalitis, as these antibodies may cross-react with NMDA receptors in the brain [15]. This mechanism has not been observed in mRCC yet. Antibodies against the NMDA receptor were not present in our patient, suggesting that other mechanisms are probably involved in the pathogenesis of checkpoint inhibitor-induced immune encephalitis.
Anti-Ma2-associated paraneoplastic neurological syndromes, such as brain encephalitis, usually present as isolated or combined limbic, diencephalic, or brainstem dysfunction [27, 28]. The presence of anti-Ma2 antibodies has been associated with neoplasms in approximately 96% of described cases [28], mainly cases of testicular cancer and small cell lung carcinoma. There is a growing body of evidence that anti-Ma2-associated encephalitis differs from typical paraneoplastic limbic or brainstem encephalitis and may therefore be unrecognized. The association of anti-Ma2 antibodies and mRCC has not been proven yet. However, the association between anti-Ma2 antibodies and immune encephalitis might be similar to that between anti-NMDA antibodies and melanoma. We cannot exclude the presence of anti-Ma2 antibodies prior to the start of checkpoint inhibitor therapy, but this finding undoubtedly contributed to the diagnosis of immune-mediated encephalitis in our patient.
The mainstay of the management of immune-mediated encephalitis is therapy with intravenously administered corticosteroids, similarly to that of other irAEs. However, therapy can be successful only if absolute compliance of the patient and his family can be guaranteed. The dose of corticosteroids depends on toxicity grade, ranging from 0.5 to 2 mg/kg per day [29]. The response to corticosteroid therapy in immune encephalitis seems to be slower and less pronounced than that in other irAEs. Therefore, higher initial doses of corticosteroids may be required. Alternatively, other immunosuppressive drugs such as infliximab can be used.
It must be emphasized that patients treated with intravenously administered corticosteroids are especially prone to infectious complications, and adequate care should be paid to this issue. The presented patient was administered trimethoprim/sulfamethoxazole as prevention against Pneumocystis pneumonia. Unfortunately, early signs of infection could not be recognized as he refused to remain in our hospital. It should therefore be recommended that patients with severe irAEs are treated in an in-patient setting in order to recognize early signs of infectious complications and start antibiotic treatment as soon as possible.
Unfortunately, we were not able to convince either our patient or his family to comply, so there was no way to extend our therapy (for example, with intravenously administered immunoglobulins or plasmapheresis) to prevent his death.
The major problem with immune checkpoint inhibitors is the relatively short-term collective experience. Hence, there is an urgent need to extend physicians' and patients' knowledge of possible complications of this promising treatment modality. This is especially important for rare but potentially fatal complications. Therefore, it is of great importance to include this topic in multidisciplinary tumor board meetings. Considering the rarity of immune checkpoint inhibitor-related encephalitis, it is essential to report such cases and share experience regarding treatment approaches and diagnostic tools. Immune-related encephalitis is a severe and potentially fatal complication requiring immediate hospital admission and extensive immunosuppressive therapy. The examination of CSF for paraneoplastic antibodies such as anti-NMDA receptor and anti-Ma2 antibodies in order to distinguish autoimmune etiology from other possible causes is essential and highly recommended.
The study was supported by the Charles University Faculty of Medicine in Hradec Králové grant (SVV- 2016-260286), UK Progres (Q40/06), to cover the fees linked with language corrections and proof reading of manuscript and further with article processing charges.
Availability of data and materials
The data acquired during the current study are available from the corresponding author on reasonable request.
Authors' contributions
JK analyzed and interpreted the patient data regarding the toxicity and was a major contributor in writing the manuscript. OK interpreted the patient data regarding the toxicity and was second major contributor in writing the manuscript. BS made substantial contributions to acquisition of data regarding the toxicity and revised manuscript critically. PH made substantial contributions to acquisition of data regarding the toxicity and revised manuscript critically. TG performed the histological examination of the kidney and brain tissue and contributed to manuscript with pathological report. MZ has been involved in drafting the manuscript, participated on interpretation of data, literature research. PP was involved in revising the draft critically for important intellectual content and participated on interpretation of data. All authors read and approved the final manuscript.
Ethics approval and consent to participate
The patient signed written consent with treatment; all collected data were acquired during the standard diagnostic procedures following internal regulations of university hospital.
Consent for publication
Written informed consent was obtained from the patient's wife for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
Competing interests
The authors declare that they have no competing interests.
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary material
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