Acute TNFα levels predict cognitive impairment 6-9 months after COVID-19 infection.

BACKGROUND: A neurocognitive phenotype of post-COVID-19 infection has recently been described that is characterized by a lack of awareness of memory impairment (i.e., anosognosia), altered functional connectivity in the brain's default mode and limbic networks, and an elevated monocyte count. However, the relationship between these cognitive and brain functional connectivity alterations in the chronic phase with the level of cytokines during the acute phase has yet to be identified. AIM: Determine whether acute cytokine type and levels is associated with anosognosia and functional patterns of brain connectivity 6-9 months after infection. METHODS: We analyzed the predictive value of the concentration of acute cytokines (IL-1RA, IL-1ß, IL-6, IL-8, IFNγ, G-CSF, GM-CSF) (cytokine panel by multiplex immunoassay) in the plasma of 39 patients (mean age 59 yrs, 38-78) in relation to their anosognosia scores for memory deficits via stepwise linear regression. Then, associations between the different cytokines and brain functional connectivity patterns were analyzed by MRI and multivariate partial least squares correlations for the whole group. RESULTS: Stepwise regression modeling allowed us to show that acute TNFα levels predicted (R2 = 0.145; ß = -0.38; p = .017) and were associated (r = -0.587; p < .001) with scores of anosognosia for memory deficits observed 6-9 months post-infection. Finally, high TNFα levels were associated with hippocampal, temporal pole, accumbens nucleus, amygdala, and cerebellum connectivity. CONCLUSION: Increased plasma TNFα levels in the acute phase of COVID-19 predict the presence of long-term anosognosia scores and changes in limbic system functional connectivity.

Frequency of Abnormally Low Neuropsychological Scores in Post-COVID-19 Syndrome: the Geneva COVID-COG Cohort.

OBJECTIVE: Several studies have reported poor long-term neuropsychological performances in patients following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but none has yet considered the effect of administering multiple intercorrelated neuropsychological tests and assessed the frequency of cognitive deficits in a normative population. Our aim was therefore to assess the presence of cumulative neuropsychological deficits in an actual post-coronavirus disease of 2019 (COVID-19) comparison group versus one simulated using Monte-Carlo methods. METHOD: Validated neuropsychological Monte-Carlo simulation methods were applied to scores from a battery of neuropsychological tests (memory, executive, attentional, perceptual, logical reasoning, language, and ideomotor praxis) administered to 121 patients who had had mild, moderate, or severe COVID-19 (mean age: 56.70 years; 32% women), 222 ± 43 days post-infection. The cumulative percentages of the three severity subgroups were compared with the results of a false discovery rate-corrected probability analysis based on normative data. RESULTS: The cumulative percentages of deficits in memory and executive functions among the severe and moderate patients were significantly higher than those estimated for the normative population. Moderate patients also had significantly more deficits in perception and logical reasoning. In contrast, the mild group did not have significantly more cumulative deficits. CONCLUSIONS: Moderate and severe forms of COVID-19 cause greater long-term neuropsychological deficits than those that would be found in a normative population, reinforcing the hypothesis of long-term effects of SARS-CoV-2 on cognitive function, independent of the severity of the initial infection.

SARS-CoV-2 and Guillain-Barré syndrome: AIDP variant with a favourable outcome.

BACKGROUND AND PURPOSE: The spectrum of COVID-19, caused by severe acute respiratory syndrome coronavirus 2 infection (SARS-CoV-2), includes different neurologic manifestations of the central and peripheral nervous system. METHODS: From March through April 2020, in two university hospitals located in western Switzerland, we examined three patients with Guillain-Barré syndrome (GBS) following SARS-CoV-2. RESULTS: These cases were characterized by a primary demyelinating electrophysiological pattern (Acute inflammatory demyelinating polyneuropathy or AIDP) and a less severe disease course compared to recently published case series. Clinical improvement was observed in all patients at week five. One patient was discharged from hospital after full recovery with persistence of minor neurological signs (areflexia). Two of the three patients remained hospitalized: one was able to walk and the other could stand up with assistance. CONCLUSIONS: We report three cases of typical GBS (AIDP) occurring after SARS-CoV-2 infection and presenting with a favourable clinical course. Given the interval between COVID-19-related symptoms and neurological manifestations (mean of 15 days) we postulate a secondary immune-mediated mechanism rather than direct viral damage.

Diagnostic value of 18-F fluorodeoxyglucose PET/CT and bone scan in Schnitzler syndrome.

Introduction: Schnitzler syndrome is an auto-inflammatory disease defined by chronic urticarial eruption and monoclonal gammopathy. 18F fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) is often performed, but its utility in Schnitzler syndrome has not been specifically investigated. The aim of this study was to determine whether PET/CT is informative in the diagnosis and follow-up of Schnitzler syndrome relative to other imaging techniques, including bone scans.Patients and methods: Patients of this study were selected from the French cohort established by Néel et al. All patients with a diagnosis of Schnitzler syndrome (according to Strasbourg's and Lipsker's criteria) who had at least one PET/CT were included. Data were collected from medical records. PET/CT scans were all reviewed by a nuclear physician blinded to the clinical and imaging data.Results: Ten patients underwent at least one PET/CT scan and all had at least one 99mTechnetium bone scan during their follow-up. The most frequent PET/CT abnormalities were diffuse bone-marrow and/or increased femoral fluorodeoxyglucose uptake, but they did not correlate with disease activity. Conversely, bone-scan abnormalities, including mainly increased radiotracer uptake in long bones, appeared to strongly correlate with Schnitzler syndrome activity.Discussion: PET/CT does not appear to be useful for the diagnosis and follow-up of Schnitzler syndrome. However, bone scans appear to be more sensitive for diagnosis and may correlate with clinical activity. Bone scans may be well positioned to distinguish Schnitzler syndrome relapse from other aetiologies of bone, joint, or muscle pain.Conclusion: Bone scans may be favoured over PET/CT in Schnitzler syndrome.

[Rituximab-induced acute thrombocytopenia in a patient with chronic lymphocytic leukemia]. / Un cas de thrombopénie aiguë au rituximab dans la leucémie lymphoïde chronique.

INTRODUCTION: Rituximab is a chimeric anti-CD20 monoclonal antibody generally well tolerated. However, a severe but rare rituximab-related immune-toxic syndrome, associating fever, chills and thrombocytopenia can occur shortly after the infusion. CASE REPORT: We report a case of severe acute rituximab-induced thrombocytopenia with favorable outcome in a patient with chronic lymphocytic leukemia and discuss the possible underlying mechanisms. CONCLUSION: Despite the potential initial severity of rituximab-induced thrombocytopenia in CLL, chemotherapy should not be discontinued; tolerance might increase as the hematologic disorder is controlled.

[Abdominal pain in progressive encephalomyelitis with rigidity]. / Encéphalomyélite progressive avec rigidité révélée par une douleur abdominale.

INTRODUCTION: Stiff-person syndrome is rare neurological disease, associating trunk rigidity and painful muscular spasms. A clinical variant of stiff person syndrome is the progressive encephalomyelitis with rigidity and myoclonus (PERM), which includes neurological cognitive disturbances. CASE REPORT: We report a 73-year-old woman initially addressed for abdominal pain, anorexia and severe weight-loss, for whom diagnosis of PERM was made. CONCLUSION: Because of its various clinical presentations, sometimes without evidence for neurological disease, the diagnosis of PERM is delayed. The presence of antineuropile antibodies associated with muscular spasms at electromyogram are strong evidence for this diagnosis.

Disseminated Mycobacterium lentiflavum responsible for hemophagocytic lymphohistocytosis in a man with a history of heart transplantation.

Mycobacterium lentiflavum is a nontuberculous, slowly growing mycobacterium usually recognized as a contaminant. Here, we report a case of disseminated M. lentiflavum infection responsible for hemophagocytic lymphohistocytosis in a heart-transplanted man.

[Granulomatosis with polyangiitis (previously Wegener's granulomatosis) mimicking malingering]. / Forme pseudo-pathomimique de granulomatose avec polyangéite (anciennement maladie de Wegener).

INTRODUCTION: ANCA vasculitis may involve the skin and develop slowly without specific histology, and without autoantibodies. CASE REPORT: We report a 50-year-old woman who experienced bilateral mastectomy because of ulcero-necrotic, non-specific inflammatory cutaneous lesions of the breasts. First considered by others as a malinger patient, she developed oto-neurological lesions leading to the diagnosis of Wegener's granulomatosis. Five years later, specific antibodies of the disease were present. CONCLUSION: Cutaneous involvement by ANCA vasculitis can be isolated for a long time. Physicians must have a high degree of suspicion to avoid diagnostic delay of ANCA vasculitis.

[Clinical, laboratory, radiological features, and outcome in 26 patients with aortic involvement amongst a case series of 63 patients with giant cell arteritis]. / Caractéristiques cliniques, paracliniques et profil évolutif de l'atteinte aortique de la maladie de Horton : à propos de 26 cas d'aortite parmi 63 cas de maladie de Horton.

PURPOSE: Aortic involvement that occurs in temporal arteritis is probably underestimated because it is usually asymptomatic. The characteristics of giant cell arteritis with aortic involvement are still poorly described and the relationship between aortitis and vascular outcome of the disease has not been clearly delineated. The objective of this retrospective study of 63 patients with giant cell arteritis, including 26 with aortic involvement, was to compare the features of patients with and without aortitis, and to assess the contribution of CT-scan and FDG-PET-scan in screening for vascular disease, monitoring, and therapeutic management of patients. METHODS: This retrospective study was conducted in the internal medicine department of the university hospital in Marseille, France, from January 1, 2005 to September 30, 2011. Patients had at least three out of the five American College of Rheumatology criteria for temporal arteritis and aortic involvement was investigated in all patients using CT-scan. Aortic wall thickness greater or equal to 3mm was considered to be abnormal. RESULTS: Of 63 patients diagnosed with giant cell arteritis, 26 (41.3%) had aortic involvement diagnosed by aortic CT-scan. Age at diagnosis was significantly younger (66.8 vs 73.8 years; P=0.002) in the group with aortitis. Inflammatory dorsal and low back pain, signs of vascular disease of the upper limbs (P=0.009), and higher level of acute phase reactants were associated with aortitis. Aneurysmal lesions of the aorta were significantly more frequent in the group with aortitis. Twenty patients had both aortic CT-scan and FDG-PET-scan. For patients in whom aortic involvement was not demonstrated with CT-scan, FDG-PET-scan was always non-contributive. With corticosteroids, aortitis resolved within 6 months in all patients as evaluated by aortic CT-scan. However, aortitis persisted in 80% of cases at 6 months when evaluated with FDG-PET-scan, and in 66% of cases at 12 months, without influencing the treatment. CONCLUSION: This case series shows no specific features of aorta and its main roots involvement in giant cell arteritis, justifying a systematic screening by CT-scan. The high frequency of this arterial involvement could help physicians in the diagnosis of giant cell arteritis. Aortitis seems to be associated with vascular complications as highlighted by the frequency of aortic aneurysm and a case of early aortic dissection. Finally, the role of PET-CT-scan for screening vascular disease and therapeutic monitoring remains to be clarified.

Cryptococcosis in sarcoidosis: cryptOsarc, a comparative study of 18 cases.

AIM: To describe the main characteristics and the treatment of cryptococcosis in patients with sarcoidosis. DESIGN: Multicenter study including all patients notified at the French National Reference Center for Invasive Mycoses and Antifungals. METHODS: Retrospective chart review. Each case was compared with two controls without opportunistic infections. RESULTS: Eighteen cases of cryptococcosis complicating sarcoidosis were analyzed (13 men and 5 women). With 2749 cases of cryptococcosis registered in France during the inclusion period of this study, sarcoidosis accounted for 0.6% of all the cryptococcosis patients and for 2.9% of the cryptococcosis HIV-seronegative patients. Cryptococcosis and sarcoidosis were diagnosed concomitantly in four cases; while sarcoidosis was previously known in 14/18 patients, including 12 patients (67%) treated with steroids. The median rate of CD4 T cells was 145 per mm(3) (range: 55-1300) and not related to steroid treatment. Thirteen patients had cryptococcal meningitis (72%), three osteoarticular (17%) and four disseminated infections (22%). Sixteen patients (89%) presented a complete response to antifungal therapy. After a mean follow-up of 6 years, no death was attributable to cryptococcosis. Extra-thoracic sarcoidosis and steroids were independent risk factors of cryptococcosis in a logistic regression model adjusted with the sex of the patients. CONCLUSIONS: Cryptococcosis is a significant opportunistic infection during extra-thoracic sarcoidosis, which occurs in one-third of the cases in patients without any treatment; it is not associated to severe CD4 lymphocytopenia and has a good prognosis.

[Ischemic cholangitis in intensive care unit: favourable outcome with ursodesoxycholic acid and fenofibrate]. / Cholangite sclérosante de réanimation : évolution favorable sous acide ursodésoxycholique et fénofibrate.

INTRODUCTION: Ischemic cholangitis in intensive care unit is a recently reported liver disease in patients who have had a prolonged mechanical ventilation and vasopressive drug support for multiple organ deficiency. Prognosis is usually poor and the only life-saving therapy is liver transplantation despite ursodesoxycholic acid treatment. CASE REPORT: We report a 63-year-old man who presented with a sclerosis cholangitis after a month in intensive care unit, effectively treated with fenofibrate and ursodesoxycholic acid. Recent reports underline fenofibrate efficacy in the treatment of primary biliary cirrhosis, especially in association with ursodesoxycholic acid. This treatment has prevented liver transplantation for our patient with a correct quality of life. CONCLUSION: The addition of fibrate to ursodesoxycholic acid improves persistent cholestasis in sclerosing cholangitis.

Continuous muscle activity, Morvan's syndrome and limbic encephalitis: ionic or non ionic disorders?

The early pathophysiologic study showed increasing evidence that autoimmunity is implicated in the pathogenesis of neuromyotonia. Antibodies to voltage gated potassium channel were detected in the serum of patients who had peripheral nerves hyperexcitability and also Morvan's disease or limbic encephalitis. These discoveries offered new approaches to treatments. Recently, antibodies previously attributed to VGKC recognise 2 surface antigens LGI1 and CASPR2 into the VGKC complex. Finally, VGKC antibodies are directed to 2 proteins the first one is a key hippocampic protein containing pre and post synaptic proteins. The second one CASPR2 is an hippocampic and paranodal protein. There clinical significance is different: hyperexcitability, limbic encephalitis without thymoma for LGI1, hyperexcitability, Morvan limbic encephalitis and frequent thymoma for CASPR2. In conclusion, the term NMT--LE--VGKC should be changed to NMT--LE with LGII and CASPR2 antibodies and classified as auto immune synaptic disorders. Mutations in genes encoding both these proteins are found in hereditary epilepsy and other syndromes. Various potassium channelopathies are closely linked to Morvan's syndromes. A new classification of antibodies will be necessary.

[Kawasaki disease in older children and young adults: 10 years of experience in Marseille, France]. / Maladie de Kawasaki chez le grand enfant et l'adulte jeune : expérience marseillaise sur 10 ans.

Kawasaki disease is a well-known disease in young children. However, it can also affect older children. The aim of this study was to determine the different characteristics of Kawasaki disease in older children and young adults. This is a descriptive, retrospective, and multicenter study including all cases of Kawasaki disease occurring in children over 8 years and adults hospitalized at children's or adult Hospitals, in Marseille, France, between 1999 and 2009. The clinical, biological, prognostic, and therapeutic data were reviewed for each case. Over a 10-year period, 98 patients were hospitalized for Kawasaki disease. Six cases were aged between 8 years and 1 month and 21 years and 7 months. All patients showed a classic form of the disease with associated organ damage in 5 patients. A cardiac problem was present in 5 cases with 2 patients needing intensive care. The median time to diagnosis and treatment was 11.2 days, with all patients initially diagnosed erroneously. Current treatment guidelines were applied in 2 patients. Kawasaki disease in children over 8 years and adults under 30 years has a worse prognosis than in young children even though clinical features are atypical. It is rarely seen by clinicians in this age group, causing a delay in diagnosis, the main factor of the poor prognosis. The diagnosis of Kawasaki disease must be raised when predisposing factors are present in this group.

[Relapsing meningitis and confusion: limbic encephalitis revealing Hodgkin's disease]. / Méningite et confusion fébrile à rechute: encéphalite limbique révélant une maladie d'Hodgkin.

INTRODUCTION: An observation of limbic encephalitis associated with Hodgkin's disease is compared with rare cases of the literature. The clinical presentation was relapsing episodes of febrile cognitive disorders with confusion and meningitis, curable after treatment of Hodgkin's disease. Recent concepts on limbic encephalitis are discussed. CASE REPORT: A seventy-five-year-old patient was hospitalized because of relapsing feverish confusion episodes with meningitis. During the year before his admission he had experienced four spontaneously regressive episodes of feverish confusion. Exploration of these episodes disclosed a paraneoplastic limbic encephalitis due to an underlying Hodgkin's disease. The treatment of Hodgkin's disease led to perfect recovery of cognitive function, so that the patient could drive his car. CONCLUSION: Lymphoproliferative disease, such as Hodgkin's disease, is a possible diagnosis in patients with limbic encephalitis. A dysimmune process underlying Hodgkin's disease might be operating in this association.