Progressive Multifocal Leukoencephalopathy Presenting as Transverse Myelitis

Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disease caused by reactivation of JC virus affecting typically subcortical and periventricular white matter of immunocompromised hosts (HIV infection, hematologic malignancies). We present an unusual case of PML predominantly affecting cervical spinal cord and brainstem in an immunocompetent host. A 65-year-old female presented with vertigo, hemiparesis and right sided weakness. MRI of the brain without contrast showed T2 signal abnormality involving the medulla extending into the upper cervical cord to C2-C3 level. Further work up showed positive ANA, elevated SS-A/Ro and SS-B/La antibodies consistent with Sjögren Syndrome. The patient deteriorated rapidly, expiring eight days after onset of acute respiratory failure. Autopsy showed multifocal white matter lesions with perivascular lymphocytic cuffing, microglial nodules, influx of activated microglial and numerous oligodendroglial nuclei with ground glass inclusions in the spinal cord, brain stem, cerebellum and cerebral hemisphere. The inclusions were immunoreactive with Simian virus-40 (SV-40), P53 and MIB-1 immunostains. The distributions of the lesions were predominantly in the medulla and upper cervical cord, correlating with pre-mortem MRI. A rare subset of PML cases can occur in association with connective tissue disorders (Sjögren in this case), Systemic Lupus Erythematosus (SLE) being the most common. Predominantly spinal involvement by PML is also rare. PML should be considered in the differential diagnosis of spinal cord/brainstem lesions, particularly in the patients with connective tissue disorders. This highlights the importance of post-mortem examination in selected cases without definite clinical diagnosis.https://scholarlycommons.henryford.com/merf2019caserpt/1068/thumbnail.jp

Predictors of Response and Outcome of Patients with Acquired Hemophilia A

Context: Acquired hemophilia A (AHA), which is caused by autoantibodies against coagulation Factor VIII, is a rare and life-threatening bleeding disorder with a mortality rate of up to 25%. The clinical characteristics and outcomes of AHA remain difficult to establish due to disease rarity. We evaluated the clinical characteristics, predictors of response and outcome of patients with AHA.Design: We retrospectively evaluated 25 consecutive patients with AHA managed at our institution from February 2007 to January 2018. The study was approved by our Institutional Review Board. Result: The median age was 73.5 years (range: 55.1 - 91.7 years); 13 (52%) were male. Underlying conditions were identified as malignancy in 8 patients (2 gastrointestinal carcinoma, 2 prostate adenocarcinoma, 2 lung carcinoma, 1 cervical carcinoma, 1 follicular lymphoma, 1 small cell lymphoma/chronic lymphocytic leukemia, 1 squamous cell carcinoma of the face) with 2 patients having more than 1 underlying malignancy. Infection was identified as the underlying cause in 2 patients (1 patient with HIV and hepatitis B and 1 patient with multiple infections with arm cellulitis). The most frequent presenting symptoms were subcutaneous/intramuscular hemorrhage (soft tissue, skin or joints) and gastrointestinal bleeding with variable severity. Twenty (80%) patients required red blood cell transfusion during admission with a median of 7 units (range: 1- 40 units). On initial presentation, Factor VIII activity was decreased in all patients (median = 1.0%; range: 0.3 - 34%) by Factor VIII inhibitor (median 30.0 Bethesda units (BU); range: 0.8 - 702 BU). Nineteen (76%) patients achieved complete remission after initiation of immunosuppressive therapy with prednisone alone (3/3 patients), prednisone with cyclophosphamide (8/10 patients), prednisone with rituximab (3/5 patients), or prednisone/cyclophosphamide/rituximab (5/7 patients). The median time to complete remission was 50 days (range: 2 - 191 days). Complete remission was achieved early (within 1 month) in patients with low titers of Factor VIII inhibitors (\u3c20 BU), whereas patients with high titers (\u3e20 BU) were likely to achieve complete remission after 30 days (odds ration = 4.33, CI: 1.61 - 11.69, p = 0.003). Patients with high Factor VIII inhibitor titers (\u3e20 BU) received more than 5 units of packed red blood cells (RBCs) as compared to patients with low titers (odds ratio = 4.33, CI: 1.14 - 38.83, p = 0.047). Only 2 patients relapsed after 10 months and 2 years, respectively. None of the patients died of treatment; only one patient died of bleeding complications. Conclusion: Most of our patients achieved complete remission after immunosuppressive therapy. High titers of Factor VIII inhibitors were predictors of delayed response (more than 1 month from presentation) and increased need for packed RBCs transfusion, consistent with an aggressive disease. Studies with larger cohorts are warranted to better determine the predictors of response and outcome in AHA.https://scholarlycommons.henryford.com/merf2019clinres/1049/thumbnail.jp

Unusual Case of Progressive Multifocal Leukoencephalopathy in a Patient With Sjögren Syndrome

ABSTRACT: Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disease caused by reactivation of John Cunningham virus affecting typically subcortical and periventricular white matter of immunocompromised hosts (human immunodeficiency virus infection, hematologic malignancies). Cerebral hemispheric white matter is most commonly affected by lytic infections, leading to progressive damage to oligodendrocytes in the central nervous system. Neuroimaging usually highlights scattered foci of white matter hypodensity not attributable to contrast enhancement or mass effect. In contrast, we present an unusual case of PML predominantly affecting cervical spinal cord and brainstem in an immunocompetent host. This is a rare subset of PML case that can occur in association with connective tissue disorders (Sjögren Syndrome in this case), systemic lupus erythematosus being the most common. Progressive multifocal leukoencephalopathy should be considered in the differential diagnosis of spinal cord or brainstem lesions, particularly in the patients with connective tissue disorders

Unusual Case of Progressive Multifocal Leukoencephalopathy in a Patient With Sjögren Syndrome.

Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disease caused by reactivation of John Cunningham virus affecting typically subcortical and periventricular white matter of immunocompromised hosts (human immunodeficiency virus infection, hematologic malignancies). Cerebral hemispheric white matter is most commonly affected by lytic infections, leading to progressive damage to oligodendrocytes in the central nervous system. Neuroimaging usually highlights scattered foci of white matter hypodensity not attributable to contrast enhancement or mass effect. In contrast, we present an unusual case of PML predominantly affecting cervical spinal cord and brainstem in an immunocompetent host. This is a rare subset of PML case that can occur in association with connective tissue disorders (Sjögren Syndrome in this case), systemic lupus erythematosus being the most common. Progressive multifocal leukoencephalopathy should be considered in the differential diagnosis of spinal cord or brainstem lesions, particularly in the patients with connective tissue disorders

P-selectin expression assay in a repeatedly serotonin-release assay-negative patient with heparin-induced thrombocytopenia

Heparin-induced thrombocytopenia (HIT) is an immune complication of heparin therapy caused by antibodies to complexes of platelet factor 4 (PF4) and heparin. Pathogenic antibodies to PF4/heparin bind and activate platelets to propagate a hypercoagulable state culminating in life-threatening thrombosis. The serotonin-release assay (SRA) is considered the gold-standard test to diagnose HIT. However, the sensitivity of the SRA was questioned with reported cases of clinical diagnosis of HIT and negative SRA. Herein, we present the utility of platelet factor 4-dependent P-selectin expression assay (PEA) in diagnosing HIT in a patient with thrombocytopenia and recurrent thrombosis who repeatedly tested negative with SRA

Thrombocytapheresis for acquired von Willebrand syndrome in a patient with essential thrombocythemia and recent multivisceral transplantation

BACKGROUND: Essential thrombocythemia (ET) is associated with increased risk of bleeding secondary to acquired von Willebrand syndrome (AVWS). Bleeding in ET requires urgent platelet reduction by cytoreductive therapy such as hydroxyurea or thrombocytapheresis. We report on the efficacy and safety of thrombocytapheresis in managing AVWS in a patient with ET and multivisceral transplantation. CASE REPORT: The patient was a 51-year-old female who underwent multivisceral transplantation. Her postoperative course was complicated by bleeding from oral cavity, IV lines, gastrointestinal and upper respiratory tracts as well as vaginal bleeding, which coincided with ET flare with a platelet count of 1512 × 10(9) /L. Coagulation studies including von Willebrand factor (vWF) antigen and activity, vWF propeptide antigen, and vWF multimer analysis were consistent with AVWS. Hydroxyurea was initiated. However, due to major bleeding, rapidly increasing platelet count, and uncertainty of response to hydroxyurea being given through the enteral tube, thrombocytapheresis was initiated for rapid platelet reduction. The patient tolerated the procedure well. Platelet count was reduced from 1636 × 10(9) /L to 275 × 10(9) /L with rapid cessation of bleeding. The patient\u27s condition stabilized over the next few days; however, bleeding recurred with increasing platelet count, which required a second thrombocytapheresis 8 days after the first one. The patient was maintained on hydroxyurea 500 mg twice/day. At 11-month follow-up, she had a normal platelet count and no recurrence of bleeding. DISCUSSION: Thrombocytapheresis is safe and efficient in managing postoperative bleeding due to ET/AVWS in solid organ transplant patients. The procedure can be an adjunct to bridging therapy before response to hydroxyurea is achieved

Metastatic carcinoma suggestive of urothelial carcinoma in the absence of known high-stage urothelial carcinoma: Analysis of clinical and pathologic parameters

Background: Urothelial carcinoma that is pT2 or higher is known to be an aggressive disease. However, we have encountered occasional biopsies of metastatic carcinoma with features suggestive of urothelial carcinoma in patients who have no known high-stage primary tumor. Design: We searched our pathology database for reports indicating metastatic carcinoma with findings suggesting urothelial carcinoma. Clinical and pathologic data were reviewed to identify patients without a known high-stage primary tumor. Results: Search identified 272 specimens showing metastatic carcinoma suggestive of urothelial carcinoma. Of these, 14 patients had no known primary tumor of pT2 or higher on comprehensive pathology and electronic medical record review, including 10 (71%) pT1, 3 (21%) carcinoma in situ, and 2 (14%) pTa. A substantial number (n=8, 57%) had tumors of the renal pelvis (n=5), ureter (n=1), or prostatic urethra (n=2). Metastatic sites included the lungs (n=4), liver (n=4), bone / soft tissue (n=3), brain (n=2), and lymph nodes (n=2). Unique patients included one with a renal pelvis high-grade papillary urothelial carcinoma concurrent with multiple sites of clear cell adenocarcinoma thought to be also of urinary tract origin. Another patient had prominent inflammatory / myxoid changes surrounding the ureter that was resected to relieve obstruction; however, no carcinoma was sampled in this specimen. Conclusions: A high proportion of patients with metastatic carcinoma suggestive of urothelial carcinoma in the absence of a high-stage primary tumor (pT2 or higher) have had a primary tumor in uncommon sites, including the renal pelvis, prostatic urethra, or ureter (57%). This raises the possibility that current staging parameters and pathologic evaluation for non-bladder primary tumors are not entirely adequate for assessing their risk