PCR In CSF Research Articles

Unforeseen Events: Seizures Following Lung Transplant

Introduction Transmission of donor-derived malignancy is rare. Angiosarcoma is one of the seldom forms of soft tissue neoplasm. We report a case of transmission of angiosarcoma Case Report A 48-year-old woman, suffering from α-1-antitrypsin deficiency, underwent double lung transplantation (DLTx) in August 2011. The multi-organ donor (heart, lungs, kidneys and liver) was a 52-year-old female without a pre-existing history of cancer, who died due to intracerebral haemorrhage. The lung recipient had an uneventful postoperative course. The patient was discharged from hospital after 23 days. Two months after DLTx the patient was readmitted after an episode of generalized seizure. CT-scan and MRI of the brain revealed multiple lesions highly suspicious of cerebral toxoplasmosis. Empirical antibiotic treatment for toxoplasmosis was initiated. Subsequent toxoplasma PCR in CSF was negative. Whole body PET-CT scan revealed multiple processes in lungs, liver, left breast, thyroid gland and lymph nodes. Breast and liver biopsies showed angiosarcoma (positive Factor 8, FLI-1 and focally CD31). Palliative radiation treatment was planned, but the patient died before initiation due to cancer progression, 93 days after the DLTx. In the liver recipient, who died 122 days after transplantation (Tx), autopsy revealed that he had also developed angiosarcoma with the same morphology and immunohistochemical pattern as the lung patient. Subsequently, the other recipient hospitals were informed. The kidney-recipients were both affected and the kidney grafts were removed, immunosuppression was stopped, and multimodal cancer therapy was initiated. One kidney recipient died 181 days after Tx due to cancer progression, whereas the other is still alive 14 months after Tx. Only the heart recipient had no signs of malignant transmission 14 months after Tx. Summary Our report presents a very rare case of transmission of donor-derived high grade angiosarcoma with a rapid and fatal outcome in three out of five recipients.

1064 Neurological Involvement of Enterovirus Infection in Young Infants with Sepsis-Like Illness

IntroductionEnterovirus (EV) infection is common in young infants. Amongst those requiring intensive care seizures and cerebral white matter abnormalities with serious neurologic sequelae have been reported. We questioned whether similar...

1130 The neurological sequelae of the measles outbreak in South Africa

IntroductionSouth Africa experienced a measles outbreak in early 2010. Measles may affect the central nervous system early as meningo-encephalitis; months later as subacute measles encephalitis (SME); or years later as...

Perinatal tuberculosis: two unusual cases

Two immunocompromised infants with perinatal tuberculosis are reported. Both presented with bilateral miliary mottling of the lungs. The first was a 4-month-old boy with a history of prolonged administration of prednisolone. He had tuberculous meningitis. Diagnosis was confirmed by PCR in serum and CSF. His mother had tuberculous endometritis. The second was a 1-month-old boy with perinatal HIV infection. Diagnosis was made by PCR in serum. Both parents were HIV-infected and had open pulmonary tuberculosis.

Chlamydophila pneumoniae DNA and mRNA transcript levels in peripheral blood mononuclear cells and cerebrospinal fluid of patients with multiple sclerosis

Chlamydophila pneumoniae DNA and mRNA transcripts were investigated by PCR and RT-PCR in fresh CSF and PBMC specimens co-cultured in Hep-2 cell lines and collected from 14 patients with definite RR MS and 19 patients with other inflammatory (OIND) and non-inflammatory (NIND) neurological controls. A positivity for C. pneumoniae DNA and mRNA was detected in CSF and PBMCs of 9 RR MS patients (64.2%) with evidence of disease activity, whereas only 3 controls were positive for Chlamydial DNA. These preliminary findings suggest that C. pneumoniae may occur in a persistent and metabolically active state at both peripheral and intrathecal levels in MS, but not in OIND and NIND.

Dengue encephalopathy in children in Northern India: Clinical features and comparison with non dengue

Acute febrile encephalopathy (AFE) is a common cause of childhood hospital admissions in Lucknow. In recent years, many patients have been hospitalized with AFE and hemorrhagic manifestations, some of whom were proven to have dengue viral infection. To (i) define the role of dengue encephalopathy (DE) as a cause of AFE in children in Lucknow, (ii) document features of dengue hemorrhagic fever (DHF) in them and (iii)compare clinical features of definite dengue and non dengue AFE. Prospective study at a teaching hospital in northern India. Children between 1-12 years of age hospitalized with fever and altered consciousness of 2 weeks or less duration were enrolled after excluding bacterial and tuberculous meningitis and frank hepatic encephalopathy. Clinical and laboratory details were charted. Haemagglutination inhibition (HI) test for dengue and Japanese encephalitis viruses in paired sera and IgM antibody capture ELISA for dengue were done. Real time PCR was done in those samples testing positive for dengue IgM. Those with either positive HI test or positive dengue PCR in CSF or serum were considered definite dengue infection and features of DHF were charted in them. Those negative for IgM antibodies after 5 days of illness or whenever done, HI test, were considered definite non dengue. Clinical and laboratory features were compared between definite dengue and non dengue groups. A total of 265 patients of AFE were enrolled over a 2 year period. HI test was positive in 15/49 (30.6%) and IgM in 52/238 (21.8%) patients thus tested. A total of 62 patients were positive for dengue antibodies by either test. Real time PCR assay for dengue virus genome was positive in 28/42 (69%) tested -- 21/29 (72.4%) in CSF and 9/15 (60%) in serum. A total of 39 patients met the criteria for definite dengue infection of which only 2 fulfilled the WHO criteria for DHF. Comparing DE and non DE, rash, bleeding, swelling over body, and hepatomegaly were significantly more common and meningeal signs less frequent in DE. Mean platelet counts and serum albumen were lower and liver enzymes and INR were significantly higher in DE. Dengue viral infection is a cause of AFE in children in this region. Majority of DE here appears to be due to viral invasion of brain as suggested by high PCR positivity in CSF and lack of WHO criteria for DHF. Differentiating features of DE include swelling and hepatic dysfunction.

Cidofovir in combination with HAART and survival in AIDS-associated progressive multifocal leukoencephalopathy

Progressive multifocal leukoencephalopathy is a demyelinating disease with a high mortality caused by the JC virus and occurs in about 5% of HIV-infected patients. Highly active anti-retroviral therapy (HAART) has a proven efficacy in prolonging the survival of patients with AIDS-associated PML, but there are differing opinions about adding cidofovir to the treatment of PML. To investigate the benefit of HAART combined with cidofovir, we retrospectively analysed the survival of 33 patients with AIDS-associated PML proven by PCR in CSF, biopsy or at autopsy. Additionally, we also analysed 37 patients with probable PML. Seventeen (51.5%) of the patients with confirmed PML were treated with HAART and 14 (42.4%) with cidofovir in any combination. Of these patients, 13 (39.4%) were treated with HAART and cidofovir in combination, four (12.1%) patients received only HAART without cidofovir and one (3%) patient received only cidofovir without HAART. Fifteen patients did not receive HAART or cidofovir. The cumulative survival was significantly longer in patients with HAART than in patients without HAART (p = 0.006), independent whether cidofovir was given or not. In comparison with single therapy with HAART, the combination of HAART and cidofovir showed no significant increase in survival (p = 0.435). Therefore, a benefit for cidofovir in addition to HAART in the treatment of PML in HIV-infected patients could not be proven.

Locked-in state due to Epstein–Barr virus primary infection in an immunocompetent patient

Sir: Guillain–Barre syndrome (GBS) can occasionally present with acute quadriparesis and abolition of brain stem reflexes [1]. We report a fulminant presentation of GBS mimicking a locked-in state during an Epstein–Barr virus (EBV) primary infection in an immunocompetent patient. A previously healthy 59-year-old woman was hospitalized because of weakness and dysaesthesia in the extremities for 24 h. One week before admission, she had had isolated fever for 72 h which had spontaneously resolved. At admission, the physical examination showed only a symmetric weakness of the legs (strength, 4/5), and preserved deep tendon reflexes. Laboratory tests showed an increase of aminotransferase plasma concentration (3N), no inflammatory syndrome, and a complete blood count normal without atypical leukocytes. The cerebrospinal fluid was normal. Magnetic resonance imaging (MRI) of the brain and the entire spine showed no abnormality. Over the next 24 h, the patient developed a flaccid quadriparesis, hyporeflexia, diplopia, difficulty in swallowing, and respiratory failure. She required intubation and mechanical ventilation. The electromyography (EMG) showed motor and sensory abnormalities in all four limbs consistent with a severe axonal polyneuropathy. A diagnosis of GBS was made and intravenous immunoglobulin (IVIg) (0.4 g/kg/day) was started. On the 4th hospital day, the patient presented full flaccid quadriplegia and absence of brain stem reflexes, in particular dilated pupils unresponsive to bright light, complete ophthalmoplegia, and no corneal reflex. An electroencephalogram (EEG) showed symmetrical 7–8 Hz activity responsive to visual and sound stimuli. Serologic tests for HIV, B and C hepatitis, Campylobacter jejuni and anti-ganglioside antibodies were negative. The results of serologic tests for EBV are shown in Table 1. EBV was not detected by PCR in CSF. After 5 days of IVIg, corticosteroids (1 mg/kg/day) were administrated for 4 weeks. The patient recovered progressively, with ocular motricity on day 9, head movement on day 15, and motricity of the arms beginning on day 30. She was extu-

Neurolisteriosis mimicking herpes simplex encephalitis in an immunocompromized patient

Brain MRI was performed in an immunocompromized febrile and lethargic patient, revealing an asymmetric bilateral temporal lobe involvement, strongly suggestive of herpetic encephalitis. Nevertheless, PCR in CSF for Listeria monocytogens was positive. This case implies that Listeria might be considered in patients with clinical and imaging suspicion of herpetic encephalitis.

0822 Clinical spectrum, pitfalls in diagnosis and therapeutic implications in herpes simplex encephalitis

High index of suspicion is mandatory for early diagnosis of Herpes Simplex Encephalitis (HSE), since acyclovir therapy can prevent its mortality and limit morbidity. We report our observations on clinical spectrum, pitfalls in diagnosis and therapeutic aspects in patients of HSE.There were 34 patients of HSE (26 males and eight females) in age range 6 -72 (mean 23.8 +/- 8.9) years. Diagnosis was confirmed by cranial MRI, EEG and PCR in CSF. Acyclovir was given to 24 patients. Carbamazepine and sodium valproate were the antiepileptic drugs used.Most of the patients were referred either as Japanese encephalitis, cerebral malaria or tubercular meningitis. High fever, seizures, behavioral abnormality and encephalopathy were present in all, either at onset or later. EEG, CSF abnormality and cranial MRI were abnormal in all 34 patients. PCR for Herpes Simplex virus was positive in 65 % cases CT was performed in 10 cases but abnormality was detected only in four. We observed features of Kluver Bucy syndrome in three patients, suffering from HSE. Following complete acyclovir therapy in 24 patients, 12 recovered completely and four partially. There was no improvement in four patients including two patients who had features of Kluver Bucy Syndrome, while four expired. Among the seven patients who refused therapy of acyclovir, five expired, while two remained in unaltered status. Treatment could not be completed in three patients as they expired during therapy.HSE is commonly misdiagnosed. Important factors influencing mortality and morbidity of HSE were; early acyclovir therapy, age, immune status of patient, duration of illness, and consciousness level before initiation of therapy. We conclude that acyclovir should be given to all patients as soon as suspected, while confirmatory investigations are in progress.

Urgences infectieuses néonatales

Early-onset neonatal infections, particularly bacterial and viral (herpes) infections, are a major concern considering the urgent need of the appropriate antiinfective therapy. The two principal etiologic agents of bacterial neonatal infections are group B Streptococcus and Escherichia coli. The diagnosis should rely on obstetrical criteria, clinical signs, microbial exams and inflammatory laboratory studies. It is only with these four data that algorithms can be elaborated. ANAES published in September 2002 new recommendations for the diagnosis and treatment of early-onset bacterial neonatal infections. Indications for antimicrobial therapy depend on whether the newborn is symptomatic or not. The recent ANAES publication gives answers to some clinical situations but some interrogations are remaining. The second emergency is the neonatal herpes simplex virus (HSV) infection. Its incidence in France is low. The most common cause of infection is intrapartum transmission. Clinical manifestations are various, HSV-2 infections are more severe than HSV-1 which is responsible for severe neurological sequellae. Diagnosis is based on specific PCR in blood and CSF. Immediate mucocutaneous protection, antiseptic soaping and intravenous acyclovir in some situations are part of the treatment. Prognosis, ameliorated with acyclovir, is conditioned by an early diagnosis.

Diagnosis of HAM/TSP based on CSF proviral HTLV-I DNA and HTLV-I antibody index.

The contribution of human T-cell lymphotropic virus (HTLV-I) DNA by PCR in CSF and the intrathecal synthesis of antibodies to HTLV-I by the antibody index (AI) to the diagnosis of HTLV-1-associated myelopathy (HAM)/tropical spastic paraparesis (TSP) were evaluated. Cases of spastic paraparesis compatible with HAM/TSP had increased AI for HTLV-I (60/73) and HTLV-I proviral sequences in CSF (25/27). Among 27 patients with other neurologic diseases, three had increased AI and another three had positive HTLV-I DNA in CSF. Thus, the combination of PCR for proviral DNA and AI for HTLV-I in CSF provides consistent criteria for the diagnosis of HAM/TSP.

Neurological manifestations of dengue infection

Severe forms of dengue, the most important arboviral infection of man, are associated with haemorrhagic disease and a generalised vascular leak syndrome. The importance of dengue as a cause of neurological disease is uncertain. During 1995, all patients with suspected CNS infections admitted to a referral hospital in southern Vietnam were investigated by culture, PCR, and antibody measurement in serum and CSF for dengue and other viruses. Of 378 patients, 16 (4.2%) were infected with dengue viruses, compared with four (1.4%) of 286 hospital controls (odds ratio [95% CI] 3.1 [1.7-5.8]). Five additional dengue positive patients with CNS abnormalities were studied subsequently. No other cause of CNS infection was identified. Seven infections were primary dengue, 13 secondary, and one was not classified. Ten patients had dengue viruses isolated or detected by PCR, and three had dengue antibody in the CSF. 12 of the 21 had no characteristic features of dengue on admission. The most frequent neurological manifestations were reduced consciousness and convulsions. Nine patients had encephalitis. No patient died, but six had neurological sequelae at discharge. Phylogenetic analysis of the four DEN-2 strains isolated mapped them with a DEN-2 strain isolated from a patient with dengue haemorrhagic fever, and with other strains previously isolated in southern Vietnam. In dengue endemic areas patients with encephalitis and encephalopathy should be investigated for this infection, whether or not they have other features of the disease.

Value of clinical symptoms, intrathecal specific antibody production and PCR in CSF in the diagnosis of childhood Lyme neuroborreliosis.

Due to the wide spectrum of clinical manifestations of Lyme neuroborreliosis laboratory investigations are necessary to confirm the diagnosis. Serum and CSF antibodies against Borrelia burgdorferi (Bb) as well as mononuclear CSF pleocytosis are usually present in patients with suspected neuroborreliosis. In some cases, however, the results may be conflicting, causing difficulty for the clinician in making a therapeutic decision. We therefore analysed the value of clinical symptoms, the presence of intrathecal antibody production against Bb with a modified IFA and a capture ELISA test, and the presence of Bb in the CSF with PCR testing in eleven children with suspected neuroborreliosis. In six of eight children with probable neuroborreliosis we could demonstrate intrathecal antibody production against Bb. In only one of these cases could Bb be detected in the CSF with the PCR assay. In two children the clinical manifestations consisting of erythema chronicum migrans and facial palsy, the presence of mononuclear CSF pleocytosis, and the presence of Bb specific antibodies in serum supported the diagnosis of neuroborreliosis, despite the absence of intrathecal specific antibodies. Three additional children with possible neuroborreliosis based on the occurrence of nonspecific clinical symptoms along with high serum antibody titers to Bb were included in the study. Intrathecal antibodies against Bb could not be detected and the PCR result was negative; therefore the diagnosis of neuroborreliosis was not substantiated in these three patients. We conclude that in addition to clinical symptoms, serological evidence and CSF findings suggestive of neuroborreliosis, the demonstration of intrathecal specific antibody synthesis against Bb may be helpful in establishing a definitive diagnosis of neuroborreliosis. The absence of CSF antibodies, however, does not necessarily indicate a lack of CNS involvement, especially if the examination is performed early in the course of disease. PCR testing in CSF is not suitable for routine application in the diagnosis of Lyme neuroborreliosis.