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Objective: To compare the efficacy of methotrexate (MTX) and mycophenolate mofetil (MMF) in the prevention of relapses in neurosarcoidosis. Methods: We conducted a retrospective multicenter study including patients who received MTX or MMF for the treatment of histologically proven neurosarcoidosis. The efficacy of the immunosuppressive drug was assessed by determining the time to relapse. Results: Forty patients with a diagnosis of neurosarcoidosis (24 men, 16 women, median age at diagnosis 43.5 years) who received at least 3 months of MTX (n = 32) or MMF (n = 14) were included. The immunosuppressive drug was always associated with steroids. The rate of relapse was 47% in the MTX group (0.2 relapses per year of exposure) and 79% in the MMF group (0.6 relapses per year of exposure) (p = 0.058). The median time to relapse was significantly shorter in the MMF group (11 months) compared with the MTX group (28 months) (p = 0.049). Adverse events occurred in 11 patients during MTX therapy and in 1 patient during MMF therapy (p = 0.12). Conclusions: Relapses of neurosarcoidosis occur frequently, despite the use of an immunosuppressive drug in addition to corticosteroids. MTX significantly increases the survival time without relapse compared to MMF and should be preferred over MMF for the treatment of neurosarcoidosis. This study provides Class IV evidence that for patients with neurosarcoidosis taking steroids, MTX is superior to MMF in reducing the risk of relapse.

Whipple disease (WD) is a rare multisystemic infection with a protean clinical presentation. The central nervous system (CNS) is involved in 3 situations: CNS involvement in classic WD, CNS relapse in previously treated WD, and isolated CNS infection. We retrospectively analyzed clinical features, diagnostic workup, brain imaging, cerebrospinal fluid (CSF) study, treatment, and follow-up data in 18 patients with WD and CNS infection. Ten men and 8 women were included with a median age at diagnosis of 47 years (range, 30–56 yr). The median follow-up duration was 6 years (range, 1–19 yr). As categorized in the 3 subgroups, 11 patients had classic WD with CNS involvement, 4 had an isolated CNS infection, and 3 had a neurologic relapse of previously treated WD. CNS involvement occurred during prolonged trimethoprim-sulfamethoxazole (TMP-SMX) treatment in 1 patient with classic WD. The neurologic symptoms were various and always intermingled, as follows: confusion or coma (17%) related to meningo-encephalitis or status epilepticus; delirium (17%); cognitive impairment (61%) including memory loss and attention defects or typical frontal lobe syndrome; hypersomnia (17%); abnormal movements (myoclonus, choreiform movements, oculomasticatory myorhythmia) (39%); cerebellar ataxia (11%); upper motor neuron (44%) or extrapyramidal symptoms (33%); and ophthalmoplegia (17%) in conjunction or not with progressive supranuclear palsy. No specific pattern was correlated with any subgroup. Brain magnetic resonance imaging (MRI) revealed a unique focal lesion (35%), mostly as a tumorlike brain lesion, or multifocal lesions (23%) involving the medial temporal lobe, midbrain, hypothalamus, and thalamus. Periventricular diffuse leukopathy (6%), diffuse cortical atrophy (18%), and pachymeningitis (12%) were observed. The spinal cord was involved in 2 cases. MRI showed ischemic sequelae at diagnosis or during follow-up in 4 patients. Brain MRI was normal despite neurologic symptoms in 3 cases. CSF cytology was normal in 62% of patients, whereas Tropheryma whipplei polymerase chain reaction (PCR) analysis was positive in 92% of cases with tested CSF. Periodic acid–Schiff (PAS)-positive cells were identified in cerebral biopsies of 4 patients. All patients were treated with antimicrobial therapy for a mean duration of 2 years (range, 1–7 yr) with either oral monotherapy (TMP-SMX, doxycycline, third-generation cephalosporins) or a combination of antibiotics that sometimes followed parenteral treatment with beta-lactams and aminoglycosides. Eight patients also received hydroxychloroquine. At the end of follow-up, the clinical outcome was favorable in 14 patients (78%), with mild to moderate sequelae in 9. Thirteen patients (72%) had stopped treatment for an average time of 4 years (range, 0.7–14 yr). Four patients had clinical worsening despite antimicrobial therapy; 2 of those died following diffuse encephalitis (n = 1) and lung infection (n = 1). In conclusion, the neurologic manifestations of WD are diverse and may mimic almost any neurologic condition. Brain involvement may occur during or after TMP-SMX treatment. CSF T. whipplei PCR analysis is a major tool for diagnosis and may be positive in the absence of meningitis. Immune reconstitution syndrome may occur in the early months of treatment. Late prognosis may be better than previously reported, as a consequence of earlier diagnosis and a better use of antimicrobial therapy, including hydroxychloroquine and doxycycline combination.

Morbidity and mortality after a totally implantable venous access port (TIVAP)-related infection in oncology patients have rarely been studied. We conducted this study to assess the incidence and factors associated with the following outcome endpoints: severe sepsis or septic shock at presentation, cancellation of antineoplastic chemotherapy, and mortality at week 12. We conducted a prospective single-center observational study including all adult patients with solid cancer who experienced a TIVAP-related infection between February 1, 2009, and October 31, 2010. Patients were prospectively followed for 12 weeks. Among 1728 patients receiving antineoplastic chemotherapy during the inclusion time, 72 had an episode of TIVAP-related infection (4.2%) and were included in the study (median age, 60 yr; range, 28-85 yr). The incidence of complications was 18% for severe sepsis or septic shock (13/72 patients), 30% for definitive cancellation of antineoplastic chemotherapy (14/46 patients who still had active treatment), and 46% for death at week 12 (33/72 patients). Factors associated with severe sepsis or septic shock were an elevated C-reactive protein (CRP) level and an infection caused by Candida species; 4 of the 13 severe episodes (31%) were due to coagulase-negative staphylococci (CoNS). Factors associated with death at week 12 were a low median Karnofsky score, an elevated Charlson comorbidity index, the metastatic evolution of cancer, palliative care, and an elevated CRP level at presentation. Hematogenous complications (that is, infective endocarditis, septic thrombophlebitis, septic pulmonary emboli, spondylodiscitis, septic arthritis, or organ abscesses) were found in 8 patients (11%). In conclusion, patients' overall condition (comorbidities and autonomy) and elevated CRP level were associated with an unfavorable clinical outcome after a TIVAP-related infection. Candida species and CoNS were responsible for severe sepsis or septic shock.

ObjectivesTo describe clinicopathologic features of muscular sarcoidosis and the associated sarcoidosis phenotype through a nationwide multicenter study.MethodsPatients were included if they had histologically proven sarcoidosis and symptomatic muscular involvement confirmed by biological, imaging, or histologic examinations.ResultsForty-eight patients (20 males) were studied, with a median age at muscular symptoms onset of 45 years (range 18–71). Four patterns were identified: a nodular pattern (27%); smoldering phenotype (29%); acute, subacute, or progressive myopathic type (35%); and combined myopathic and neurogenic pattern (10%). In all patterns, sarcoidosis was multivisceral with a median of 3 extramuscular organs involved (mostly lungs, lymph nodes, eyes, and skin) and a prolonged course with long-term use of corticosteroids and immunosuppressive drugs. Muscular patterns differed according to clinical presentation (myalgia, nodules, or weakness), electromyographic findings, muscular MRI, and response to sarcoidosis treatment. The myopathic and neuromuscular patterns were more severe.ConclusionThis nationwide study of muscular sarcoidosis allowed the identification of 4 patterns of granulomatous myositis, which differed by phenotypes and the clinical course.

Purpose Susac syndrome is a rare microangiopathy of the brain, retina, and cochlea that mainly affects young women. We studied the management of this disease using retinal fluorescein and indocyanine green angiographies. Methods Retrospective, observational case series of seven patients with Susac syndrome identified in ophthalmology and internal medicine departments. We reviewed medical, ophthalmologic, and angiographic records at study enrollment and during long-term treatment. Mean follow-up was 37 months. Best-corrected visual acuity, intraocular inflammation score, ophthalmoscopy data, automated perimetry score, and fluorescein and indocyanine green angiographic features were analyzed with the results of cerebral magnetic resonance imaging and spinal fluid analysis and ENT signs. Results Retinal fluorescein angiography showed focal nonperfused retinal arterioles with hyperfluorescent walls in all cases. Indocyanine green angiography showed normal choroidal circulation. Retinal vasculitis was uncontrolled in a patient treated with steroids. Improvement of retinal arteriole perfusion occurred during immunosuppressive treatment with cyclophosphamide. Conclusion Absence of intraocular inflammation and focal, labile nonperfused retinal arterioles with integrity of choroidal circulation are monomorphic ophthalmologic features that could immediately suggest the diagnosis of Susac syndrome. Early ophthalmologic examination aided by retinal fluorescein angiography could be useful for managing cases of unexplained neurologic symptoms in women.

Susac syndrome is characterized by the clinical triad of encephalopathy, hearing loss, and retinal artery branch occlusions, mostly in young women. To our knowledge, long-term outcome and impact of pregnancy have not been specifically addressed. We report a series of 9 patients (7 female, 2 male) followed at the same institution, with special emphasis on clinical outcome including pregnancy and long-term sequelae. Clinical, brain magnetic resonance imaging (MRI), funduscopy, retinal angiography, and audiogram data were recorded every 3-12 months. We also analyzed the 92 previously reported cases of Susac syndrome. Mean follow-up was 6.4 years. Age at onset was 30.4 years. The first symptom occurred between April and September in 7 of 9 patients in the current study, and in 68% of all patients. The complete triad at onset was clinically obvious in only 1 of 9 patients. Brain involvement was heralded by headache and symptoms of encephalopathy. Cerebrospinal fluid was abnormal in 5 patients showing pleocytosis (mean, 24.6; range, 6-85 cells/mL) and elevated protein level (mean, 210; range, 113-365 mg/dL). Over time, quantitative brain MRI analysis showed that the number of lesions diminished and did not parallel clinical flares, and MRI never normalized. At the end of follow-up, no patient had severe impairment, and all but 1 returned to work. Inner ear involvement was present at onset in 2 patients and occurred in others with a mean delay of 11 months. Initially unilateral in 3, it became bilateral in all. Mean hearing loss was 34 dB (range, 15-70 dB). Hearing loss never improved, either spontaneously or under treatment. The eye was involved at onset in 8 patients, and after 3 years in 1. All had multiple bilateral retinal artery branch occlusions and/or dye leakage with hyperfluorescence of the arterial wall on fluorescein angiography. Over time, angiography normalized in 3 patients. In others, it was still abnormal at the end of follow-up (range, 1.5-10 yr). On late findings, fluorescein leakage was more frequent than true arterial occlusion. Eye involvement was mostly asymptomatic, unilateral, peripheral, and resumed spontaneously to remit in other sites over time. Corticosteroids were efficient to treat encephalopathy, with relapses occurring when the dosage was tapered. Steroid treatment did not improve hearing loss or prevent new retinal arteriolar occlusions. Anticoagulation had a role in treating encephalopathy and retinal arteriolar occlusions. Three patients had 4 pregnancies. Two pregnancies needed induced abortion. One pregnancy was uneventful. One pregnancy was complicated with Susac disease flare in the early postpartum period. In conclusion, at the end of follow-up, most patients had returned to work and none had severe impairment. Pregnancy may affect the course of Susac syndrome, with relapse of encephalopathy postpartum. Our main finding was that the course of Susac syndrome is not self-limited as previously thought, since isolated retinal arteriolar involvement may occur as a very late manifestation.

A 51-year-old woman originating from Africa presented to our institution with newly intermittent claudication, headache, and dyspnea associated with a 4-month history of weight loss and tiredness. Clinical examination showed hypertension and a marked pressure gradient between the upper and lower limbs (140/80 versus 80/50 mm Hg). There was no sign of digestive claudication or renal insufficiency. Computed tomography angiography demonstrated an 80% segmental stenosis of the descending thoracic aorta associated with aortic wall thickening >95 mm in length (Figure A), together with pulmonary infiltrates and cervicomediastinal lymphadenopathies. Combined positron emission tomography-computed tomography showed a hypermetabolism of the aortic thickening (Figure B) and cervicomediastinal lymphadenopathies. The surgical biopsy of a cervical lymphadenopathy showed the presence of granuloma consistent with a tuberculosis infection. Figure. A , PET scan showing hypermetabolism of aortic thickening. B …

Susac syndrome is an occlusive arteriolar disease that provokes infarcts in the cochlea, retina, and brain of young subjects, mostly women. Its cause is unknown. Some infarcts may be asymptomatic and only revealed by ancillary investigation: 1) audiogram that shows bilateral sensorineural hearing loss predominating on low frequencies, 2) funduscopy and fluorescein retinal angiography demonstrating bilateral distal branch retinal artery occlusions, and 3) brain MRI T2-weighted images disclosing small multifocal hyperintensities in white and gray matter. Treatment options are not codified, ranging from antithrombotic drugs to immunomodulatory therapy. Course is self-limited after an active fluctuating phase. Dementia, blindness, and deafness are rare late sequelae, and half of patients return to normal life.

The use of 18F-fluoro-deoxyglucose positron emission tomography scan (FDG-PET) and computed tomography angiography (CTA) to improve accuracy of diagnosis of giant cell arteritis (GCA) is a very important clinical need. We aimed to compare the diagnostic performance of FDG-PET and CTA in patients with GCA.FDG-PET and CTA were acquired in all consecutive patients suspected for GCA. Results of FDG-PET and CTA were compared with the final diagnosis based on clinical judgment, temporal artery biopsy (TAB) findings, and ACR criteria. Sensitivity, specificity, and positive and negative predictive values (PPV, NPV) were calculated for each method.Twenty-four patients suspected for GCA were included. Fifteen (62.5%) were ultimately diagnosed as having GCA. Among them, all fulfilled ACR criteria and 6 had biopsy-proven GCA. Strong FDG uptake in large vessels was found in 10 patients who all had GCA. Mean maximal standard uptake values (SUVmax) per patient measured at all the arterial territories were of 3.7 (range: 2.8-4.7). FDG uptake was negative in 14 patients including 9 and 5 patients without and with GCA, respectively. Mural thickening suggestive of aortitis or branch vessel arteritis was observed on CTA in 11 patients with and 2 patients without GCA. No mural thickening was observed in 11 patients including 7 patients without and 4 patients with GCA. Overall, sensitivity was 66.7% and 73.3%, specificity was 100% and 84.6%, NPV was 64.3% and 64.6%, and PPV was 100% and 84.6% of FDG-PET and CTA, respectively.Both FDG-PET and CTA have a strong diagnostic yield for the diagnosis of GCA. FDG-PET appeared to have a higher PPV as compared to CTA and may be the preferred noninvasive technique to explore patients with suspected GCA.

Up to 50% patients with sarcoidosis display extra-pulmonary disease. However, initial and isolated (ie, without lung disease) acute muscular involvement associated with pseudo-malignant hypercalcemia is very uncommon. We report on 3 cases of life-threatening hypercalcemia revealing florid and isolated acute sarcoid-like myositis.All patients complained of fatigue, progressive general muscle weakness, and weight loss. Laboratory tests showed a severe life-threatening hypercalcemia (>3.4 mmol/L). Hypercalcemia was associated with increased serum level of 1,25-(OH)2 vitamin D and complicated with acute renal failure. One patient displayed acute pancreatitis due to hypercalcemia.In all cases, PET-scan, performed for malignancy screening, incidentally revealed an intense, diffuse, and isolated muscular fluorodeoxyglucose (FDG) uptake consistent with diffuse non-necrotizing giant cells granulomatous myositis demonstrated by muscle biopsy. Of note, creatine phosphokinase blood level was normal in all cases. No patients displayed the usual thoracic features of sarcoidosis.All patients were treated with high dose steroids and achieved rapid, complete, and sustained remission. A review of English and French publications in Medline revealed 5 similar published cases.Steroid-sensitive acute sarcoid-like myositis causing high calcitriol levels and life-threatening hypercalcemia should be recognized as a separate entity.

Cardiovascular disease (CVD) is the main cause of death in systemic lupus erythematosus (SLE) patients. We aimed to determine whether overweight (defined as a body mass index [BMI] > 25 kg/m2) contributed to subclinical atherosclerosis in SLE patients at low risk for CVD according to traditional factors. Wall thickness of the internal carotid artery (ICWT) measured at the carotid bulb and carotid plaques were assessed in 49 SLE patients asymptomatic for CVD and 49 controls matched on Framingham score. Factors associated to ICWT were identified and multivariate analysis was performed. SLE patients and controls displayed a low 10-year risk for CVD according to Framingham score (mean 1.9 ± 3.5 in SLE vs 1.8 ± 3.2% in controls, P = 0.37). ICWT (P

Recognizing giant cell arteritis (GCA) in patients with stroke may be challenging. We aimed to highlight the clinical spectrum and long-term follow-up of GCA-specific cerebrovascular accidents. Medical charts of all patients followed in a French Department of Internal Medicine for GCA between January 2008 and January 2014 were retrospectively reviewed. Patients with cerebrovascular accidents at GCA diagnosis were included. Diagnosis of GCA was based on American College of Rheumatology criteria. Transient ischemic attacks and stroke resulting from an atherosclerotic or cardioembolic mechanism were excluded. Clinical features, GCA-diagnosis workup, brain imaging, cerebrospinal fluid (CSF) study, treatment, and follow-up data were analyzed. From January 2008 to January 2014, 97 patients have been followed for GCA. Among them, 8 biopsy-proven GCA patients (mean age 70±7.8 years, M/F sex ratio 3/1) had stroke at GCA diagnosis. Six patients reported headache and visual impairment. Brain MR angiography showed involvement of vertebral and/or basilar arteries in all cases with multiple or unique ischemic lesions in the infratentorial region of the brain in all but one case. Intracranial cerebral arteries involvement was observed in 4 cases including 2 cases with cerebral angiitis. Long lasting lesions on diffusion-weight brain MRI sequences were observed in 1 case. All patients received steroids for a mean of 28.1±12.8 months. Side effects associated with long-term steroid therapy occurred in 6 patients. Relapses occurred in 4 patients and required immunosuppressive drugs in 3 cases. After a mean follow-up duration of 36.4±16.4 months, all but 1 patient achieved complete remission without major sequelae. The conjunction of headache with vertebral and basilar arteries involvement in elderly is highly suggestive of stroke associated with GCA. Intracranial cerebral arteries involvement with cerebral angiitis associated with long lasting brain lesions on diffusion-weight brain MRI sequences may occur in GCA. Both frequent relapses and steroid-induced side effects argue for the use of immunosuppressive agents combined with steroids as first-line therapy.