West Nile virus neuroinvasive disease associated with rituximab therapy.

West Nile virus neuroinvasive disease (WNVND) manifests with meningitis, encephalitis, and/or acute flaccid paralysis. It represents less than 1% of the clinical syndromes associated with West Nile virus (WNV) infection in immunocompetent patients. Immunosuppressive therapy is associated with increased risk of WNVND and worse prognosis. We present a patient with WNVND during therapy with rituximab, and a review of the literature for previous similar cases with the goal to describe the clinical spectrum of WNVND in patients treated specifically with rituximab. Our review indicates that the most common initial complaints are fever and altered mental status, brain magnetic resonance imaging often shows bilateral thalamic hyperintensities, and cerebrospinal analysis consistently reveals mild lymphocytic pleocytosis with elevated protein, positive WNV polymerase chain reaction, and negative WNV antibodies. Treatment is usually supportive care, with intravenous immunoglobulins (IVIG) plus corticosteroids and WNV-specific IVIG also used. The disease is usually fatal despite intervention. Our patient's presentation was very similar to prior reports, however demonstrated spontaneous improvement with supportive management only. WNVND is a rare and serious infection with poor prognosis when associated with rituximab therapy. Diagnosis is complicated by absent or delayed development of antibodies. The presence of bilateral thalamic involvement is a diagnostic clue for WNVND. There is insufficient evidence to recommend the use of corticosteroids or IVIG.

Infectious causes and outcomes in patients presenting with cerebral spinal fluid pleocytosis.

To evaluate the infectious etiologies, clinical features, and outcomes of patients with CNS infections at a tertiary care center. Patients that present with a pleocytosis in the cerebral spinal fluid (CSF), defined as a CSF WBC count > 5 cells/mm3, from July 2015 to June 2016 at a tertiary care hospital were analyzed for this report. Data from patients with confirmed (n = 43) and presumed (n = 51) CNS infections were analyzed. CNS infection was the leading known cause of CSF pleocytosis (n = 43, 18% of all patients with a pleocytosis in the CSF), and HSV-2 was identified as the leading causative pathogen (n = 10) followed by varicella zoster virus (n = 5). Fifty-three percent of patients with a pleocytosis in the CSF did not receive a diagnosis. In the patients that did not receive a diagnosis, CNS infection was presumed to be the cause in 51 patients (21% of patients with CSF pleocytosis). The mean time to diagnosis for patients with confirmed CNS infection was 16 days, but time to diagnosis was highly variable depending on the causative pathogen. There was a significant overlap in CSF parameters and peripheral white blood cell counts in patients diagnosed with a viral, bacterial, or fungal infection. Neuroimaging changes were present in only 44% of CNS infections. The overall mortality was 7% for CNS infections, and 17% of patients with a CNS infection had a severe neurologic deficit at presentation while only 3% had a severe deficit at the last neurologic assessment. This study provides new insights into the infectious causes of disease in a cohort of patients with pleocytosis in the CSF. The study provides new insights into the time to diagnosis and outcomes in patients that present with pleocytosis in the CSF.

Acyclovir resistance in herpes simplex virus type I encephalitis: a case report.

Acyclovir resistance is rarely seen in herpes simplex virus (HSV) type I encephalitis. Prevalence rates vary between 0.5 % in immunocompetent patients (Christophers et al. 1998; Fife et al. 1994) and 3.5-10 % in immunocompromised patients (Stranska et al. 2005). We report a 45-year-old, immunocompetent (negative HIV antigen/antibody testing), female patient, without previous illness who developed-after a febrile prodromal stage-aphasia and psychomotor slowing. Cerebral magnetic resonance imaging (cMRI) showed right temporal and insular T2-hyperintense lesions with spreading to the contralateral temporal lobe. Cerebrospinal fluid (CSF) analysis yielded lymphocytic pleocytosis and elevated protein level. Polymerase chain reaction testing for HSV type I showed a positive result in repeat lumbar puncture. HSV type I encephalitis was diagnosed and intravenous acyclovir treatment was initiated (750 mg t.i.d.). Acyclovir treatment was intensified to 1000 mg t.i.d., due to clinical deterioration, ongoing pleocytosis and progression on cMRI 5 days after initiation of antiviral therapy. In parallel, acyclovir resistance testing showed mutation of thymidine kinase gene at position A156V prompting foscarnet therapy (60 mg t.i.d.). Patient's condition improved dramatically over 2 weeks. Acyclovir resistance is rare but should be considered in case of clinical worsening of patient's condition. To our knowledge, this is the first report of acyclovir resistance in HSV type I encephalitis of an immunocompetent and previously healthy patient in Austria.

Radiology case of the month. 55-year-old female with shortness of breath and cough.

A 55-year-old African-American woman presents with progressive shortness of breath, non-productive cough, and muscle aches for two weeks. Her medical history is non-contributory. She is a current smoker with a 20-year history of smoking one pack per day. Vital signs and oxygen saturation are normal. Physical exam reveals crackles over the right middle lobe of her lung. The remainder of her physical exam is unremarkable. Blood tests demonstrate a mild leukocytosis.

Ultrasonography for leukocytosis or elevated C-reactive protein.

BACKGROUND/AIMS: Patients with abdominal symptoms and leukocytosis or elevated C-reactive protein were subjected to abdominal ultrasonography (US) for correct diagnosis. METHODOLOGY: Patients with abdominal symptoms, leukocytosis and elevated C-reactive protein were enrolled. Those with abnormal liver enzymes or radiographs were excluded since either of them might be a clue to proper diagnosis, such as hepatobiliary diseases or bowel obstruction. RESULTS: Total number of patients was 38. Number of acute diverticulitis, colitis, acute appendicitis and enteritis were 8, 7, 7 and 6, respectively. One patient with pelvis tumor and 2 with colon cancer were successfully diagnosed with abdominal US. Colon cancers were confirmed and pelvis tumor was diagnosed as ovarian squamous cell carcinoma with surgical specimens. Sensitivity and specificity were 100% (95% CI: 44-100%) and 97.1% (95% CI: 85-99%), respectively. CONCLUSIONS: Our data clearly recommended that abdominal US be performed carefully for patients with abdominal symptoms and leukocytosis or elevated CRP since potentially they had malignancies.

Pretreatment tumor-related leukocytosis misleads positron emission tomography-computed tomography during lymph node staging in gynecological malignancies.

The accuracy of fluorine-18-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG-PET/CT) can be influenced by the increased glycolytic activity of inflammatory lesions. Here, using clinical data obtained from gynecological cancer patients, tumor samples and animal models, we investigate the impact of pretreatment tumor-related leukocytosis (TRL) on the diagnostic performance of 18F-FDG-PET/CT in detecting pelvic and paraaortic lymph node metastasis. We demonstrate that pretreatment TRL misleads 18F-FDG-PET/CT during lymph node staging in gynecological malignancies. In the mechanistic investigations, we show that the false-positive 18F-FDG-PET/CT result for detecting nodal metastasis can be reproduced in animal models of TRL-positive cancer bearing G-CSF expressing cervical cancer cells. We also show that increased 18F-FDG uptake in non-metastatic nodes can be explained by the MDSC-mediated premetastatic niche formation in which proinflammatory factors, such as S100A8 or S100A9, are abundantly expressed. Together, our results suggest that the MDSC-mediated premetastatic niche created in the lymph node of TRL-positive patients misleads 18F-FDG-PET/CT for detecting nodal metastasis.

[Spinal dural arteriovenous fistula presented with rapidly progressive myelopathy, longitudinally extensive spinal cord lesion, pleocytosis with polymorphonuclear predominance, and decreased cerebrospinal fluid glucose levels: a case report].

A 75-year-old woman developed low back pain, weakness of the lower extremities, and urinary retention. On day 7 after the onset of symptoms, she was brought to the emergency department of our hospital by an ambulance because of progressive weakness of both lower extremities. Spine MRI showed longitudinally extensive spinal cord lesion (LESCL) at the Th8-Th11 spinal cord level and flow voids around the lesions. Lumbar puncture revealed a normal opening pressure, yellowish appearance, pleocytosis with polymorphonuclear predominance, and decreased cerebrospinal fluid (CSF) glucose levels. Based on the rapidly progressing myelopathy, LESCL, and CSF findings, we initially diagnosed the patient with myelitis and administered acyclovir and high-dose intravenous immunoglobulin on day 7. Spine MRI with gadolinium-enhancement showed longitudinally extending flow voids of the thoracic cord, and digital subtraction arteriogram (DSA) revealed arteriovenous shunt on the dura with dilated and tortuous intradural veins. We finally diagnosed her with spinal dural arteriovenous fistula (SDAVF). Cases of SDAVF might be initially misdiagnosed as myelitis because of showing rapid progressive myelopathy, pleocytosis with polymorphonuclear predominance, and decreased CSF glucose levels. Lumbar puncture and steroid administration for the cases of SDAVF could aggravate the patient's neurological symptoms. Therefore, lumbar puncture and initiation of immunotherapy should be avoided until SDAVF is completely excluded in patients with suspected myelitis on spine MRI without gadolinium-enhancement, even if their neurological symptoms progress rapidly.

Does CSF pleocytosis have a predictive value for disease course in MS?

Objective: MS is a demyelinating CNS disorder with a spectrum of clinical patterns regarding course and prognosis. Although several prognostic factors are considered in the initial evaluation of patients, biological markers defining the disease course and guiding treatments are currently lacking. It is unknown whether patients with CSF pleocytosis differ in regard to symptoms, disease course, and prognosis from those without. The aim of this study was to evaluate whether CSF pleocytosis during the initial presentation has an impact on the clinical course and progression of MS. Methods: We retrospectively evaluated patients attending the MS Clinic at Rabin Medical Center between January 1999 and January 2016 who underwent lumbar puncture (LP) at disease presentation, considering CSF cell count, clinical diagnosis (clinically isolated syndrome [CIS] and relapsing-remitting MS [RRMS]), annualized relapse rate (ARR), paraclinical findings (imaging, CSF oligoclonal bands, and evoked potentials), and disease progression, expressed by the Expanded Disability Status Scale (EDSS). Results: One hundred fourteen patients (72 females) underwent LP at disease presentation (RRMS: n = 100, CIS: n = 14). Age at diagnosis was 32.4 ± 12.2 years, and the follow-up time was 9.4 ± 3.8 years. Forty-six patients showed a pleocytic CSF (≥5 cells per µL). Compared with patients with <4 cells per µL, patients with pleocytosis had a higher ARR (0.60 ± 0.09 vs 0.48 ± 0.04; p = 0.0267) and a steeper increase (slope) in the EDSS score throughout the follow-up period (correlation coefficient: r2 = 0.04; p = 0.0251). Conclusions: CSF pleocytosis may be considered a biological unfavorable predictive factor regarding disease course and progression in MS.

Endovascular Treatment of Intracavernous Internal Carotid Aneurysm Secondary to Pituitary Infection.

BACKGROUND: Intracavernous internal carotid artery (ICICA) aneurysm secondary to pituitary infection is exceedingly rare. CASE DESCRIPTION: We report an unusual case of a 63-year-old man who presented with acute left blepharoptosis and imaging findings of a pituitary infection. Interestingly, sudden onset of right blepharoptosis occurred after anti-infective therapy for 10 days. Digital subtraction angiography revealed a right ICICA aneurysm. After 6 months of follow-up visits, enlargement of the ICICA aneurysm was observed, and the endovascular technique of a low-profile visualized intraluminal support stent combined with 5 detachable coils was successfully performed to treat the ICICA aneurysm, with preservation of the internal carotid artery. CONCLUSION: This rare case highlights a life-threatening complication of a pituitary infection. Moreover, enlargement of the infected ICICA aneurysm could not be relieved by conservative anti-infective therapy. Endovascular treatment may be an alternative therapy for an infected ICICA aneurysm.

Renal cell carcinoma with paraneoplastic leucocytosis.

Paraneoplstic leukocytosis, seen in some solid tumors, is due to increased production of granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, interleukin 6 and other cytokines by tumor cells. Though its association with malignancy of lung, ovary and bladder is not uncommon, but it is rarely seen with renal cell carcinoma. We are presenting such an association with papillary cell carcinoma of the kidney.

Hyperleukocytosis, an unusual paraneoplastic manifestation of lung cancer: Case report and review of literature.

Leukocytosis may be found in patients with lung cancer either at time of diagnosis or during the course of the disease. Though mild leukocytosis is common in lung cancer, hyperleukocytosis defined as total leukocyte count more than 100,000 is uncommon. We describe a 68-year-old chronic smoker who presented with osteolytic pelvic bone lesion and hyperleukocytosis, who on evaluation was found to have a primary lung cancer. Bone marrow aspiration and biopsy showed marked myeloid hyperplasia. Myeloid series comprised predominantly mature neutrophils and stab forms. Cytogenetic investigation showed a normal chromosome set (46, XY). Repeated cultures from blood, urine, and sputum were sterile. He was started on chemotherapy but had a progressive downhill course. In patient with lung cancer, leukocytosis can be due to infection, use of corticosteroid or hematopoetic growth factors, bone marrow involvement, or paraneoplastic manifestation. Paraneoplastic leukocytosis is associated with poor prognosis and aggressive disease.

Tumoral calcinosis after an injection of recombinant human erythropoietin in a dialysis patient.

Tumoral calcinosis is a rare form of soft tissue calcifications, initially described as an idiopathic condition, which could occur in uremic patients. Despite its distinct clinical and morphologic presentations, the underlying pathogenesis is unknown. We present a dialysis patient who developed tumoral calcinosis over the right shoulder after receiving a misplaced injection of human recombinant erythropoietin probably into the periarticular tissue. This case serves as an example highlighting the importance of periarticular inflammatory reaction in precipitating the development of the lesion in predisposed patients.

Acute myeloblastic leukemia associated with hyperleukocytosis and diabetes insipidus.

Two cases with acute myeloblastic leukemia (AML M4-FAB) associated with diabetes insipidus (DI) are presented here. Both patients presented with hyperleucocytosis. One had a white blood cell count (WBC) of 150 x 10(9)/L and the second patient had 200 x 10(9)/L. One of these patients was a 40 year-old male and MRI of the hypophysis showed an infindibuler mass. This patient did not respond to remission induction chemotherapy and reinduction chemotherapy was given. The other patient was a 16-year-old male with a normal CT scan of the head. Both patients had DI with typical clinical and laboratory findings. The first patient died early on during reinduction chemotherapy and the second patient died of intracranial bleeding before induction chemotherapy was given. These findings are consistent with the data in the literature suggesting that the prognosis of AML associated with DI is poor and that these cases generally present with hyperleucocytosis.

Self-limited recurrent multifocal neurological symptoms, headache, and cerebrospinal fluid lymphocytic pleocytosis: a benign syndrome with a predilection for young adult men.

Two young men, aged 34 and 30 years, developed transient recurrent multifocal neurological symptoms with associated severe headache over a 2-week period. Both had a lymphocytic pleocytosis in their cerebrospinal fluid. Cranial imaging studies were normal. All symptoms resolved without recurrence. Although the cause and pathogenesis are undefined, this self-limited benign neurological syndrome may be more common than previously recognized and has a predilection for young adult men.

[Effects of treatment with OKT3 on brain perfusion in a heart transplant patient with SPET with 99mTc-HMPAO]. / Efecto sobre la perfusión cerebral del tratamiento con OKT3 en paciente con trasplante cardíaco mediante SPET con HMPAO-99mTc.

A heart transplant patient treated with OKT3 developed a severe headache which worsened and was accompanied by a sudden decrease in the patient's consciousness level and aphasia when the treatment course was completed. CT was performed and was normal. SPET imaging with 99mTc-HMPAO of cerebral blood flow done 16 hours later revealed multiple and clear focal defects in the blood flow. Analysis of cerebral spinal fluid revealed aseptic pleocytosis. Five days after the completion of treatment, the symptoms remitted and a new control SPET 3 weeks later was completely normal. A diagnosis of neurotoxicity secondary to OKT3 administration was established.

Cranial imaging findings in dengue virus infection.

BACKGROUND: The aim of this study is to evaluate cranial CT or MRI changes in dengue encephalitis and their correlation with clinical and biochemical findings. METHODS: Twenty-one serologically confirmed patients with dengue with altered sensorium were included who underwent MRI (20)/CT (1) scan study. Their clinical details including seizure, hypotension, bleeding diathesis, focal neurologic deficit, and Glasgow Coma Scale (GCS) score were noted. Blood counts, hematocrit, renal and liver function tests, electrolytes, cerebrospinal fluid (CSF) and ECG were done. MRI findings on T1, T2, FLAIR, DWI and T1 gadolinium contrast were noted. RESULTS: The median age of the patients was 30 (5-69) years and 5 were females. MRI was abnormal in 9(45%) and CT scan in 1 patient with dengue shock syndrome revealed cerebellar and subdural hematoma. The MRI lesions were in thalamic and basal ganglia in 3, focal cortical areas in 3, white mater in 2 and meningeal enhancement in 3 patients. Seven of these patients had CSF pleocytosis. The presence of abnormal imaging was not related to outcome. One patient died, 1 was bed ridden and 19 had complete recovery on discharge. CONCLUSION: Cranial imaging reveals nonspecific changes and is not related to hematological and biochemical changes or outcome.