Neurotrophins and Migraine.

Neurotrophins (NTs) have been implicated in generation and modulation of nociceptive pathways. Change in NTs levels is associated with painful conditions and neurological diseases such as migraine. Currently, it is generally recognized that migraine headaches result from the activation and sensitization of trigeminal sensory afferent fibers leading to neuropeptides release such as calcitonin gene-related peptide (CGRP) and substance P (SP). This triggers an inflammatory cascade causing a neurogenic inflammation. The agents responsible for trigeminal activation and release of neuropeptides are still unclear. It is known that the transient receptor potential vanilloid receptor-1 (TRPV1) is an important mediator of CGRP and SP release. TRPV1 is closely associated with tyrosine receptors kinases (Trk), which are NTs receptors. NTs can act on TRPV1 increasing its sensitivity to painful stimuli, therefore predisposing to hyperalgesia. Upregulation of ion channels and pain receptors in dorsal root ganglion neurons may be alternative mechanisms by which NTs contribute to pain development. Only a few studies have been performed to investigate the role of NTs in migraine. These studies have reported changes in NTs levels in migraine patients either during the migraine attack or in free-headache periods.

Cognitive impairment and optic nerve axonal loss in patients with clinically isolated syndrome.

OBJECTIVE: To investigate cognitive impairment, to assess optical nerve axonal loss, and to determinate whether there is correlation between optical nerve axonal loss and cognition impairment in Clinically Isolated Syndrome (CIS). METHODS: Fifteen CIS patients and 15 controls were submitted to Wechsler memory scale, Rey Auditory Verbal Learning, Rey Complex Figure, Paced Auditory Serial Addition, Digit Span, verbal fluency, stroop color, D2, and Digit Symbol tests. CIS patients were evaluated by optical coherence tomography (OCT) (23 eyes). RESULTS: CIS patients had worse performance in Paced Auditory Serial Addition Test (PASAT) 2 seconds (P=0.009) and fluency tests (P=0.0038). Optical nerve axonal loss was found more frequently in eyes with previous optic neuritis (ON) (85.7%) than in those without previous ON (21.7%) (P=0.0146). There were no significant correlations between optical nerve axonal loss and cognitive findings. CONCLUSIONS: CIS patients had worse cognitive performance than controls. OCT can detect axonal loss resulting from optical neuritis and subclinical axonal loss in eyes without previous optical neuritis. Optical nerve axonal loss was not correlated with cognition.

Headache features in patients with dengue virus infection.

The aim of this study was to describe the frequency and features of headache among patients with confirmed dengue virus infection and to compare the headache features in patients with dengue fever and dengue haemorrhagic fever, primary and secondary dengue infection, and patients with and without neurological involvement. Patients with classic dengue fever had a more intense headache than those with the more severe form of the disease, dengue haemorrhagic fever.

Complications following transjugular intrahepatic portosystemic shunt: a retrospective analysis.

Transjugular intrahepatic portosystemic shunt (TIPS) has been the therapeutic option for severe decompensation of chronic liver disease and as a bridge to liver transplantation. The aim of this study was to analyze the complications of this procedure. The records of 47 patients (39 men) of mean age 48 years underwent TIPS procedures from 1998 to 2003 were reviewed. Forty-one patients received 45 successful TIPS; it failed in six patients. Improvement was observed in 20 of 28 patients with upper gastrointestinal bleeding (71%); 9 of 11 with ascites (82%); and 5 of 8 with impaired renal function (62%). The Child-Pugh scores improved in 6 of the 47 patients (13%). Transplantation was performed in 11 patients (23%). The complications were: encephalopathy (49%); infection (19%); renal failure (17%); TIPS migration to the portal vein (4%) and to the right atrium (4%). Mortality was 32% (15/47) over 3 months. Eight patients developed active bleeding during TIPS installation requiring mechanical ventilation and intensive care, and died within the first week. Other causes of death were sepsis (n = 2), liver failure (n = 1), accidental puncture of the Glisson's capsule leading to intra-abdominal bleeding (n = 1) and refractory upper gastrointestinal bleeding (n = 3). The latter four patients had TIPS placement failure. In conclusion, TIPS produced clinical improvement among 51% of patients with complications in 49%. The main complications were encephalopathy (49%), infection (19%), and renal failure (17%). The 3-month mortality rate after TIPS placement was 32%.

[Alternative diagnoses among suspected herpes simplex encephalitis patients with negative polymerase chain reaction]. / Diagnósticos alternativos em pacientes com suspeita de encefalite por Herpes simplex e negativos à reação em cadeia por polimerase (PCR).

The aim of this study was to analyze the diagnosis found in a series of patients in which the diagnosis of Herpes simplex encephalitis (HSE) was ruled out by a negative polymerase chain reaction (PCR) result for HSV DNA in cerebrospinal fluid (CSF) samples. Forty three out of 61 HSE suspected patients had negative PCR. An alternative diagnosis was established in 41.9% of these patients. These patients were diagnosed as having viral (2 cases-11.1%) and non viral (5 cases-27.2%) CNS infections, vascular (4 cases-22.2%) and demyelinating diseases (3 cases-16.7%), metabolic disturbances (3 cases-16.7%), and CNS tumor (1 case-5.6%). The non specific clinical presentation of this disease and the availability of an efficient treatment for HSE explain why several patients with other diseases were initially treated with acyclovir. The early use of PCR in CSF was considered essential for the evaluation of the acute encephalitis cases in this study.

Application of competitive PCR to cerebrospinal fluid samples from patients with herpes simplex encephalitis.

The purpose of the present study was to determine if the quantity of herpes simplex virus (HSV) DNA in the cerebrospinal fluid (CSF) of patients with herpes encephalitis would be useful in establishing the prognosis of the disease and to determine the effect of antiviral therapy on the clearance of viral DNA from the CSF. Quantitation of HSV DNA was done by constructing an internal standard (IS) from the glycoprotein B amplicon which had a 25-bp deletion between primer annealing sites. Each CSF specimen was coamplified with the IS and the ratio of the amount of HSV/amount of IS was compared to the ratios on a standard curve constructed with the same IS plus known amounts of HSV DNA. CSF specimens were available from 16 patients who were treated with intravenous acyclovir, and the amount of HSV DNA ranged from < 25 to 18,000 copies per microliter in CSF obtained before or within 4 days of the initiation of acyclovir therapy. Patients with > 100 copies of HSV DNA per microliter were older, were found by computed tomography to have lesions, and had poorer outcomes than patients with < 100 copies. Follow-up CSF specimens were available from seven patients. In six of these seven patients, the HSV DNA levels decreased during therapy. One patient had a twofold increase in HSV DNA levels after 1 week of therapy and died on day 8. The application of this assay may be helpful in establishing the prognosis and in the monitoring of patients with herpes simplex encephalitis.

Diagnosis of herpes simplex encephalitis by magnetic resonance imaging and polymerase chain reaction assay of cerebrospinal fluid.

The early diagnosis of herpes simplex encephalitis (HSE) is essential because early introduction of antiviral therapy can significantly reduce the mortality of this disease. Herpes simplex virus (HSV) DNA detection in cerebrospinal fluid (CSF) samples is a rapid, noninvasive, specific, and highly sensitive method for HSE diagnosis. Neurodiagnostic methods have also been studied for noninvasive diagnosis of HSE. Magnetic resonance imaging (MRI) seems to be the most sensitive of them but it has not been compared to PCR in terms of efficacy for HSE diagnosis. In this study, 17 patients with focal encephalitis were prospectively evaluated by PCR analysis of CSF samples and MRI examination. MRI lesions involving the inferomedial region of one or both temporal lobes were observed in all PCR-positive patients but one. No PCR-negative patient presented with the same pattern of MRI lesions. MRI was also important for the establishment of an alternative diagnosis in three of eight PCR-negative patients. Both methods should be routinely applied in the evaluation of presumed HSE cases.

Molecular detection and isolation of human T-cell lymphotropic virus type I (HTLV-I) from patients with HAM/TSP in São Paulo, Brazil.

BACKGROUND: Infection with HTLV-I is etiologically linked with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). However some patients with chronic progressive paraparesis resembling HAM/TSP have been shown to be infected with HTLV-II. OBJECTIVE: To clarify the role of each of these human retroviruses in the etiology of HAM/TSP in São Paulo, Brazil. STUDY DESIGN: A detailed serological and molecular analysis of HTLV-I/II infection was performed in a cohort of 19 patients with HAM/TSP attending a neurological clinic. RESULTS: Plasma samples analyzed for anti-HTLV-I/II antibodies using a Western blot assay, comprising HTLV-I (rgp46I)- and HTLV-II (rgp46II)-specific recombinant env epitopes, demonstrated reactivity to rgp46I and hence were typed as seropositive for HTLV-I. Presence of HTLV genomic sequences in peripheral blood mononuclear cells (PBMC) was sought after by PCR using consensus primers SK 110 and SK 111 for the pol region of HTLV proviral DNA followed by hybridization with type-specific probes--SK 112 (HTLV-I) and SK 188 (HTLV-II). Southern blots from all individuals hybridized with SK 112 but not with SK 188, further confirming HTLV-I infection. Cocultivation of PBMC from eight of these patients with activated lymphocytes from normal individuals resulted in active viral production, detected as presence of soluble p24gag antigen in culture supernatants. Investigation of risk factors for HTLV-I infection in these individuals revealed that five out of 19 patients studied (26.3%) had received blood transfusions previous to disease onset.

Human T cell lymphotropic virus type-1-associated myelopathy/tropical spastic paraparesis in Sao Paulo, Brazil: association with blood transfusion.

Human T cell lymphotropic virus type-1 (HTLV-1) associated myelopathy/tropical spastic paraparesis (HAM/TSP) has been epidemiologically linked to prior blood transfusion. The prevalence of transfusion as a risk factor for infection varies among endemic areas. Here we report the relative frequency of reported history of blood transfusion among 52 patients evaluated in Sao Paulo, Brazil. A patient reported history of blood transfusion prior to the onset of symptoms, found in 15 (28.8%) of the patients, was the most important risk factor identified in this group of patients when compared with a history of sexually transmitted diseases, homo/bisexuality, sexual promiscuity (three or more sexual partners a year), and intravenous drug use. The mean time between reported transfusions and the onset of symptoms was longer than previously reported. There was no trend toward a more severe evolution to motor inability among the HAM/TSP patients with a history of previous transfusion.

Evaluation of the range of clinical presentations of herpes simplex encephalitis by using polymerase chain reaction assay of cerebrospinal fluid samples.

Detection of DNA from herpes simplex virus in cerebrospinal fluid (CSF) samples by polymerase chain reaction (PCR) analysis has been shown to be more sensitive and specific for the diagnosis of herpes simplex encephalitis than isolation of herpes simplex virus from biopsy specimens of brain tissue. Because of the invasiveness of brain biopsy, it has been suggested that PCR analysis of CSF may reveal a wider spectrum of the disease than has been previously recognized by brain biopsy studies. In this study, PCR assay of CSF samples obtained from 29, 12, and 8 patients with focal, mild, and diffuse encephalitis, respectively, was performed. PCR assay was positive for 15 (51.7%) of 29 patients with focal encephalitis and three (25%) of 12 patients with mild encephalitis. The correlation between temporal abnormalities shown by electroencephalography, computed tomography of the brain, or cranial magnetic resonance imaging and a positive PCR assay was high. PCR analysis has revealed that atypical and less severe forms of encephalitis are caused by herpes simplex virus.

Advantage of polymerase chain reaction in the diagnosis of herpes simplex encephalitis: presentation of 5 atypical cases.

Four case of herpes encephalitis (HSVE) are described. The diagnosis was established by polymerase chain reaction (PCR) assay of cerebrospinal fluid (CSF). These reports illustrate different situations in the clinical management of this disease. PCR was considered useful in confirming the HSVE diagnosis in 3 atypical cases, and in the differentiation between virologic failure and postinfectious encephalitis in a patient with recurrence of symptoms. A case with typical HSVE clinical findings is also reported where PCR was negative and a temporal lobe lymphoma was diagnosed at autopsy. This last case is representative of the utility of PCR in the management of other diseases mimicking HSVE.

Human T lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis in São Paulo, Brazil.

We conducted a prospective clinical and epidemiologic evaluation of 45 cases of human T lymphotropic virus type I (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in São Paulo, Brazil. All enrolled patients had progressive chronic myelopathy and high titers of HTLV-I and HTLV-II antibodies, as determined by enzyme immunoassay and western blot. In 24 cases, the polymerase chain reaction (PCR) was performed so that HTLV-I could be distinguished from HLTV-II. The clinical and epidemiologic features of the patients from our study were similar to those of patients with HAM/TSP from other areas of endemicity for HTLV-I except that more patients in our study had received a blood transfusion prior to their illness. Despite the presence of HTLV-II virus in Brazil, all patients whose serum was tested by PCR were found to be infected with the HTLV-I virus.