Non-inflammatory cerebrospinal fluid delays the diagnosis and start of immunotherapy in anti-NMDAR encephalitis.

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a form of autoimmune encephalopathy that presents with a wide variety of symptoms, including neuropsychiatric manifestations. The authors' aim for this study was to analyze the results of paraclinical studies of patients with a diagnosis of anti-NMDAR encephalitis and the association between symptom onset and diagnosis, and start of immunotherapy. Retrospective data of 29 patients with anti-NMDAR encephalitis were gathered and analyzed. Abnormal EEG was found in 27 patients (93.1%), whereas MRI was abnormal in 19 patients (65.5%). In contrast, an inflammatory pattern on CSF analysis was found in only 13 patients (44.8%). The absence of pleocytosis or increased proteins in the CSF was associated with a longer time from symptom onset to diagnosis and treatment (p = 0.003). The authors conclude that noninflammatory CSF may delay the correct diagnosis and start of immunotherapy in anti-NMDAR encephalitis. In the presence of suggestive clinical features, extensive studies including EEG are recommended.

Non-inflammatory cerebrospinal fluid delays the diagnosis and start of immunotherapy in anti-NMDAR encephalitis / La ausencia de hallazgos de inflamación en líquido cefalorraquídeo retrasa el inicio de inmunoterapia en la encefalitis anti-NMDAR

ABSTRACT Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a form of autoimmune encephalopathy that presents with a wide variety of symptoms, including neuropsychiatric manifestations. The authors' aim for this study was to analyze the results of paraclinical studies of patients with a diagnosis of anti-NMDAR encephalitis and the association between symptom onset and diagnosis, and start of immunotherapy. Retrospective data of 29 patients with anti-NMDAR encephalitis were gathered and analyzed. Abnormal EEG was found in 27 patients (93.1%), whereas MRI was abnormal in 19 patients (65.5%). In contrast, an inflammatory pattern on CSF analysis was found in only 13 patients (44.8%). The absence of pleocytosis or increased proteins in the CSF was associated with a longer time from symptom onset to diagnosis and treatment (p = 0.003). The authors conclude that noninflammatory CSF may delay the correct diagnosis and start of immunotherapy in anti-NMDAR encephalitis. In the presence of suggestive clinical features, extensive studies including EEG are recommended.

RESUMEN La encefalitis por receptor anti-N-metil-D-aspartato (anti-NMDAR) es una encefalopatía autoinmune con una amplia variedad de síntomas, incluyendo manifestaciones neuropsiquiátricas. Nuestro objetivo en este estudio fue analizar los resultados paraclínicos de pacientes diagnosticados con encefalitis anti-NMDAR y la asociación entre inicio de sintomatología, el diagnóstico y el inicio de inmunoterapia. Encontramos un EEG anormal en 27 pacientes (93.1%), así como IRM anormal en 19 de ellos (65.5%). En contraste, el análisis de LCR mostró un patrón inflamatorio en tan solo 13 pacientes (44.8%). La ausencia de pleocitosis o proteínas incrementadas en el LCR se asoció con un mayor tiempo desde el inicio de la sintomatología hasta el inicio del tratamiento (p=0.003). Concluimos que el LCR no inflamatorio puede retrasar el diagnóstico correcto y el inicio de tratamiento en encefalitis anti-NMDAR, por lo que se recomienda la realización de estudios exhaustivos, incluyendo EEG, ante la presencia de indicadores clínicos sugerentes del padecimiento.

Traumatic lumbar punctures in infants hospitalized in the neonatal intensive care unit.

Traumatic lumbar punctures occur frequently in the neonatal intensive care unit, making the interpretation of cerebrospinal fluid values difficult. We report correction factors for cerebrospinal fluid protein and white blood cells in the face of red blood cell contamination. These correction factors should facilitate the diagnosis of bacterial meningitis in highrisk hospitalized infants.

Correction of cerebrospinal fluid protein for the presence of red blood cells in children with a traumatic lumbar puncture.

We sought to determine the relationship between cerebrospinal fluid (CSF) protein and CSF red blood cells in children with traumatic lumbar punctures. For every 1000 cell increase in CSF red blood cells per mm(3), CSF protein increases by 1.1 mg/dL (95% CI, 0.9-1.1 mg/dL).

An appraisal of blood-cerebrospinal fluid barrier dysfunction during the course of Guillain Barré syndrome.

BACKGROUND: Elevated cerebrospinal fluid (CSF) total protein (TP) concentration (mainly due to a dysfunctional blood-CSF barrier (B-CSFB)) with normal cell count is a hallmark for the diagnosis of Guillain-Barriota syndrome (GBS). AIMS: This work presents the evaluation of B-CSFB dysfunction with respect to the course, severity, and clinical features of GBS. MATERIALS AND METHODS: A sample of CSF was collected on admission from 68 patients of both genders (15 children and 53 adults) diagnosed with GBS. A follow-up CSF sample was obtained approximately 15 days after admission. TP concentration was determined in the CSF and 7.5% polycrylamide gel electrophoresis was employed for serum and CSF protein fractioning. A low percentage of prealbumin fraction was considered a test of impaired B-CSFB. RESULTS: Elevated TP concentration and lower prealbumin were observed in almost 70% of the patients on admission, but this percentage was lower (52.4%) during the first week from onset of symptoms. Both variables were directly associated with the time of evolution of the disease and also with a greater clinical severity. Follow-up CSF studies showed higher CSF TP and lower prealbumin percentages, while deceased patients did not display this response pattern in the follow-up CSF. CONCLUSIONS: B-CSFB dysfunction was present in only half of the patients with GBS during the first week from onset and it was directly associated with progression and clinical severity; nevertheless, a low B-CSFB dysfunction response during follow-up was associated with a lethal outcome, suggesting it could also serve a 'protective' effect during regeneration.

Intrathecal immunoglobulin G synthesis and brain injury by quantitative MRI in multiple sclerosis.

OBJECTIVES: It was the aim of this study to evaluate if the quantitative intrathecal immunoglobulin G (IgG) synthesis correlates with the brain atrophy and the total lesion volume (TLV) in brain magnetic resonance imaging (MRI) of multiple sclerosis (MS) patients. METHODS: A total of 50 patients with relapsing-remitting MS were included in this study. MRIs were performed and cerebrospinal fluid samples were collected during the diagnostic determination when patients were in remission without treatment. RESULTS: At study baseline, IgG index values were elevated in 36 patients (72%), and oligoclonal IgG bands were positive in 42 of 50 patients (84%). Brain MRI was abnormal in 94% of patients, and, compared with healthy controls, brain atrophy was observed in MS patients. A positive correlation among IgG index, cerebrospinal fluid leukocyte count and TLV was observed; the Expanded Disability Status Scale correlated positively with TLV and the number of lesions, although a significant relationship between disability and brain atrophy was not demonstrated. CONCLUSIONS: Although new parameters will be necessary in longitudinal studies to characterize the axonal injury in various stages of the disease, the data suggest that the high intrathecal IgG synthesis may predict a greater brain lesion burden.

Postictal cerebrospinal fluid abnormalities in children.

OBJECTIVES: To determine the frequency and characteristics of seizure-induced cerebrospinal fluid (CSF) abnormalities in children and to identify potential alternative causes of these findings. METHODS: Consecutive patients (n = 80) who underwent lumbar puncture within 24 hours after a seizure were studied retrospectively. The presence of CSF abnormalities in total leukocytes, polymorphonuclear cells, and protein was determined by using age-specific reference values. Coexisting conditions that could affect CSF findings, such as traumatic lumbar puncture, concurrent neurologic disease, and undiagnosed meningitis, were identified. RESULTS: Eighteen of the 80 patients were excluded from the final study group because of the presence of another condition that could alter the CSF. More than 50% of the excluded patients had an abnormal CSF leukocyte count or protein level, including 2 patients with initially undiagnosed meningitis, which was subsequently detected by post-hoc polymerase chain reaction testing. In the remaining 62 patients, postictal pleocytosis was detected in only 3 (5%), and increased protein was detected in only 6 (10%). The maximal postictal pleocytosis and protein level were 8 x 10(6) leukocytes/L (8 leukocytes/mm(3)) and 0.52 g/L (52 mg/dL), respectively. CONCLUSIONS: Seizure-induced CSF abnormalities are rare in children, and alternative, often unidentified, disease processes may account for many observed postictal abnormalities. All patients with abnormal CSF after a seizure should be thoroughly evaluated for other causes of the abnormality.

Abnormal proteins in the cerebrospinal fluid of a patient with Creutzfeldt-Jakob disease following administration of human pituitary growth hormone.

A Brazilian case of Creutzfeldt-Jakob disease in a hypopituitary patient who had received cadaver-derived human pituitary growth hormone between 1968 and 1977 is reported. The clinical diagnosis was confirmed during his lifetime by the demonstration of two abnormal 30-kDa proteins in the cerebrospinal fluid by two-dimensional gel electrophoresis. These proteins, characteristic of Creutzfeldt-Jakob disease, present isoelectric points of 5.1 and 5.2. Furthermore, both proteins migrate as doublets, each one displaying a molecular weight variant of about 29-kDa. This is one of 16 cases of the disease associated to therapy with cadaver-derived human growth hormone and one of the few examples among such cases of confirmation of the clinical diagnosis by biochemical characterization of abnormal proteins in the cerebrospinal fluid.

Abnormal proteins in the cerebrospinal fluid of a patient with Creutzfeldt-Jakob disease following administration of human pituitary growth hormone

A Brazilian case of Creutzfeldt-Jakob disease in a hypopituitary patient who had received cadaver-derived human pituitary growth hormone between 1968 and 1977 is reported. The clinical diagnosis was confirmed during his lifetime by the demonstration of two abnormal 30-kDa proteins in the cerebrospinal fluid by two-dimensional gel electrophoresis. These proteins, characteristic of Creutzfeldt-Jakob disease, present isoelectric points of 5.1 and 5.2. Furthermore, both proteins migrate as doublets, each one displaying a molecular weight variant of about 29-kDa. This is one of 16 cases of the disease associated to therapy with cadaver-derived human growth hormone and one of the few examples among such cases of confirmation of the clinical diagnosis by biochemical characterization of abnormal proteins in the cerebrospinal fluid