Mixed effect modeling of sumatriptan pharmacokinetics during drug development. I: Interspecies allometric scaling

A sample of 22 subjects was studied from a population of adults who had suffered from bacterial meningitis in childhood. Audiovestibular, oculomotor and neuropsychological investigations were performed and quality of life was assessed. An age-matched control group of 20 subjects was recruited. In the meningitis group, nine subjects had abnormal pure tone audiograms. One was previously undiagnosed and a progression was found in four. There was an overrepresentation of subclinical vestibular pathology (6 out of 9 (67%)) in this group. Audiovestibular test results showed a peripheral pattern and oculomotor tests were normal. The quality of life scores of those with hearing loss were significantly higher than those in the control group. Neuropsychological tests of brain dysfunction were abnormal in six out of 22 (27%) who had recovered from meningitis. The prevalence of such dysfunctions was not related to audiovestibular disorder. The quality of life scores of those with brain dysfunctions were similar to those of the control group. The findings of reduced auditory memory and tone level perception in four out of 22 (18%), suggest that lesions of central auditory pathways may follow from bacterial meningitis. The results support the idea that inner ear damage is the major cause of hearing loss after bacterial meningitis. Despite the absence of brainstem involvement, central nervous system lesions with disturbed auditory processing and language functions can be of significance. The high frequency of discrete brain dysfunctions indicate that a thorough neuropsychological investigation is required after bacterial meningitis.     

Sensorineural hearing loss caused by NSAID-induced aseptic meningitis

Aseptic meningitis is a rare complication of nonsteroidal anti-inflammatory drug (NSAID) use. Otologic symptoms may include sensorineural hearing loss and tinnitus. A 66-year-old woman sought the care of an otologist for sudden bilateral sensorineural hearing loss and a substantial increase in baseline tinnitus. The patient had previously undergone a left tympanoplasty secondary to cholesteatoma and had been treated for atypical face pain with ibuprofen taken every six hours for three months. Magnetic resonance imaging (MRI) with gadolinium demonstrated abnormal enhancement of the dura mater and the surrounding basal cisterns, with extension of enhancing dura mater into the internal auditory canals. Cerebrospinal fluid examination revealed evidence of aseptic meningitis. An audiogram confirmed new bilateral sensorineural hearing loss. Hearing loss and tinnitus resolved and no abnormalities were observed with MRI when nonsteroidal anti-inflammatory medication was discontinued. Otolaryngologists are well aware of the otologic sequelae in patients with meningitis. However, NSAIDs need to be considered as possible causal agents in the evaluation of meningitis with otologic symptoms.     

Pappataci fever

Sandfly fever virus is known to cause pappataci fever. The sandfly fever virus belongs to the Genus Phlebovirus (family: Bunyaviridae) and is endemically found in areas of South Europe, Asia and Africa. In Germany, pappataci fever is only described in connection with travelling to endemic areas. We report on a 15 year-old girl suffering from sandfly fever virus infection after vacation in Turkey. The initial symptoms started with fever for about three days, frontal headache, nausea and arthralgia. After a short time of clinical improvement symptoms recurred and our patient entered hospital with signs of severe meningitis. Liquor analysis showed a lymphocytic meningitis. Due to multiple insect bites on her legs sandfly fever was suspected. Blood analysis confirmed an acute infection with sandfly virus Sicilian from which she completely recovered. ELISA and immunoblot analysis revealed an infection with sandfly virus serotype Sicilian, which was not encountered with meningitis so far. Our case report illustrates that due to increased tourism sandfly fever virus infection has to be considered as a cause of aseptic meningitis in travellers.     

Prognosis for survival and improvement in function in children with severe developmental disabilities

OBJECTIVE: To evaluate the feasibility and cost-effectiveness of using transient evoked otoacoustic emissions (TEOEs) to assess hearing in infants recovered from meningitis. METHODS: Recordings of TEOEs and visual reinforcement audiometry (VRA) were performed in a prospective study of 39 children aged 6 to 24 months recovering from a purulent meningitis. Patients with no TEOEs, or whose VRA findings were abnormal, were also tested by impedance audiometry and recording of auditory brain-stem responses (ABRs) after treatment of any secretory otitis media. Costs were compared with those of a previous protocol including VRA, impedance audiometry, and ABR for all children. RESULTS: A total of 29 children had TEOEs in both ears and normal VRA findings. Ten children lacked TEOEs in one or both ears; 9 of them had otitis media with effusion. Further examination by VRA and ABR led to the diagnosis of bilateral sensorineural hearing loss in 2.6% (1/39) of patients and unilateral sensorineural hearing loss in 7.7% (3/39) of patients. Cost analysis revealed that this protocol costs about half the previous one. CONCLUSION: Recording TEOEs appears to be a feasible and cost-effective hearing screening test for infants recovered from meningitis. If TEOEs are absent, impedance audiometry, ABR recordings, and audiometric evaluation techniques are needed to distinguish between conductive and sensorineural hearing loss and to assess hearing thresholds precisely.     

ERPs in schizophrenia: effects of antipsychotic medication

Thirty unmedicated schizophrenics were compared to 29 age-matched controls on auditory and visual event-related brain potential (ERP) paradigms. Twenty-one of these patients were tested again after 1 week on placebo and after 4 weeks on antipsychotic medication. Before treatment, N1, N2, and P3 components of the auditory ERP were smaller in the schizophrenics than in the controls. Although visual N2 was smaller in schizophrenics, visual P3 was not. In spite of significant clinical improvement with antipsychotic treatment, amplitudes of auditory and visual N1, N2, and P3 were not significantly changed. Higher blood levels of antipsychotic medication were related to reductions in auditory P3 latency, however. In addition, higher levels of cerebrospinal fluid (CSF) MHPG (methoxyhydroxyphenylglycol) were associated with larger auditory N1s and larger auditory and visual P3s, suggesting an influence of arousal on these components in schizophrenics. In spite of this influence, reduction of the auditory P3 in schizophrenia is an enduring trait of the disease, which is not affected by antipsychotic medication or clinical improvement.     

Multicenter evaluation of the Amplicor Enterovirus PCR test with cerebrospinal fluid from patients with aseptic meningitis. The European Union Concerted Action on Viral Meningitis and Encephalitis

The Amplicor Enterovirus PCR test was compared with viral culture for the detection of enteroviruses in cerebrospinal fluid (CSF) specimens. In a multicenter study in which nine laboratories participated, a total of 476 CSF specimens were collected from patients with suspected aseptic meningitis. Sixty-eight samples were positive by PCR (14.4%), whereas 49 samples were positive by culture (10.4%), demonstrating that the Amplicor Enterovirus PCR test was significantly more sensitive than culture (P < 0.001). After discrepancy analysis the sensitivity and specificity of the Amplicor Enterovirus PCR test obtained by using viral culture as the "gold standard" were 85.7 and 93.9%, respectively. Our results with the CSF specimens collected in different countries demonstrate that the Amplicor test is capable of detecting a large variety of enterovirus serotypes and epidemiologically unrelated isolates in CSF specimens from patients with aseptic meningitis. The Amplicor Enterovirus PCR test is a rapid assay which can be routinely performed with CSF samples and is an important improvement for the rapid diagnosis of enteroviral meningitis.     

Importance of intensive therapy in the treatment of purulent meningitis (author's transl)

In recent years the lethality of purulent meningitis has not fallen significantly in spite of antibiotic therapy. Aspects are indicated which complicate the successful treatment of purulent meningitis, and in addition the problems of artificial respiration, the provocation of cerebro-organic paroxysms by high dose penicillin therapy, the not uncommonly observed hemorrhagic diatheses, disturbances of acid-base balance and the results of neuropathologic and echoencephalographic investigations are discussed. In addition to beginning treatment early and selective antibiotic therapy, intensive medical measures can contribute to an improvement in the prognosis of purulent meningitis.     

Effect of auditory deprivation on visual resolving power.

Conducted 2 experiments in which changes in the critical flicker fusion (CFF) were determined during and after auditory deprivation (silence). In Exp I, 36 male undergraduates were exposed to 1 wk of auditory deprivation, measurements of the CFF being taken at daily intervals and at Days 1, 2, 3, and 7 after the termination of the experimental condition. Results show that the experimental group exhibited a significant progressive improvement in visual resolving power as a function of auditory deprivation and, following its termination, a gradual decline towards the pre-experimental baseline. On the other hand, 2 control conditions, a group of confined Ss, and a non-confined group showed no systematic changes in the CFF. In Exp II with 6 new Ss, the period of auditory deprivation was extended to 14 days. Results again reveal a progressive improvement on the CFF during the 1st wk of silence followed by an asymptotic performance during the 2nd wk. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Trimethoprim and sulfonamide-associated meningoencephalitis with MRI correlates

Early recognition of trimethoprim and sulfonamide-induced aseptic meningitis is important because drug cessation leads to rapid clinical improvement. We present clinical and laboratory findings in two typical cases. In both cases, MRI revealed previously undescribed diffuse white matter abnormalities that resolved within a few months. These MRI findings are important because they may aid in early diagnosis of this condition in the appropriate clinical setting. In addition, the white matter abnormalities suggest an encephalitic component in addition to the meningitis.     

Professional education and assessment practices in central auditory processing

A 17-item questionnaire probing professional preparation and current practices in central auditory assessment was mailed to 500 audiologists selected randomly from the membership directory of the American Academy of Audiology. Data from 183 respondents, representing a 37 percent response rate, were analyzed. The majority of respondents reported minimal academic and clinical preparation in assessment of the central auditory nervous system. Eighty percent of respondents had not taken any graduate course explicitly dedicated to central auditory processing. However, 80 percent had taken at least one basic science course in central audition and 83 percent reported having taken at least one graduate course that included some coverage of central auditory processing and/or the central auditory nervous system. A mean of 3 clinical clock hours accrued in this area was reported. Not surprisingly, 78 percent reported a satisfaction rating of < or =50 percent relative to the graduate education they received in this area and only 41 percent reported providing central auditory assessment. Comparisons with prior surveys show substantial change in the preferred test battery. Most notable is the pivotal role of physiologic measures, with the acoustic reflex and auditory brainstem response listed along with the SCAN as the three most frequently used assessment tests/procedures. Overall, the results suggest a need for improvement in professional preparation in evaluation of central auditory function.     

Differential diagnosis of decreased vision: a case study

Three patients who suffered transitory (from 18 to 49 days) cranial dyskinesias during the course of tubercular meningitis are described. The diagnosis was confirmed by the presence of acid-alcohol resistant bacilli in spinal fluid. Cranial tomography or magnetic resonance images failed to demonstrate anatomical lesions. The blink reflex and brain stem auditory evoked potentials were abnormal, indicating dysfunction of motor nuclei of the cranial nerves, possibly secondary to changes in their regulation by basal ganglia. No recurrences have been observed during follow-up (from 3 to 7 years).     

Treatment of cryptococcal meningitis with combination itraconazole and flucytosine

The results of an open study of the efficacy of itraconazole and flucytosine in 10 patients with cryptococcal meningitis are reported. The outcome revealed eight responding cases (cure in 4 cases and improvement in 4 cases), and two failure cases. One patient had a relapse which responded to amphotericin B and flucytosine. No toxicity was observed.     

Lyme disease in Mato Grosso do Sul State, Brazil: report of three clinical cases, including the first of Lyme meningitis in Brazil

The authors report the occurrence of the first three clinical cases of Lyme disease in Mato Grosso do Sul State, including the first case of Lyme meningitis in Brazil. These were identified by clinical and laboratorial criteria. Anti-Borrelia burgdorferi antibody search was carried out through ELISA and Western Blotting techniques, the former providing identification of IgG class antibodies alone, in one only of those cases. Through Immunoblotting, the following features were found in serum: 5 IgG and 2 IgM bands for the first case; 7 IgG and 2 IgM bands for the second; and 5 IgG and 6 IgM bands for the third. In the latter, presence fo specific antibodies was searched in liquor, due to lymphomonocitary meningitis occurrence, and one IgM band was detected. After antibiotic therapy, all patients exhibited significant clinical and laboratorial improvement in their conditions along with symptom regression to the present moment.     

Age-related deficits in auditory confrontation naming.

The naming of manipulable objects in older and younger adults was evaluated across auditory, visual, and multisensory conditions. Older adults were less accurate and slower in naming across conditions, and all subjects were more impaired and slower to name action sounds than pictures or audiovisual combinations. Moreover, there was a sensory by age group interaction, revealing lower accuracy and increased latencies in auditory naming for older adults unrelated to hearing insensitivity but modest improvement to multisensory cues. These findings support age-related deficits in object action naming and suggest that auditory confrontation naming may be more sensitive than visual naming. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Otoacoustic emissions in full-term newborns at risk for hearing loss

Distortion product otoacoustic emissions (DPOEs) and click-evoked otoacoustic emissions (CEOEs) characteristics of the normal newborn population have been previously reported in the literature. There is little information about DPOE evaluations in the newborn population at risk for hearing loss. The authors now report the DPOE and/or CEOE data from six full-term subjects at risk for hearing loss or with highly suspected hearing loss. These subjects were less than 1 year of age and at risk for hearing loss secondary to a history of hereditary hearing loss, meningitis, hyperbilirubinemia, and ototoxic drug exposure. Audiometric evaluation included auditory brainstem responses (ABR), behavioral observation audiometry, and tympanometry. The CEOEs and DPOEs were found to be decreased or absent in the subjects with suspected hearing loss secondary to cochlear pathology; they were found to be normal in a subject with a suspected central hearing loss. This study's data suggest that otoacoustic emissions when combined with ABR can provide a frequency-specific evaluation of cochlear function and help determine the anatomic site of a pathologic lesion.     

Cerebrospinal fluid leukocyte aggregation in meningitis

OBJECTIVE: To evaluate whether the difference in aggregation of cerebrospinal fluid cells from patients with bacterial, viral, aseptic and partially treated meningitis can be used for diagnostic purposes. METHODS: Cerebrospinal fluid samples of 100 patients with meningitis (15 bacterial, 13 partially treated, 10 viral and 62 aseptic) were compared on the basis of the predefined leukocyte aggregation score (LAS). RESULTS: Mean LAS was 56% in the bacterial meningitis group (range, 15 to 90%), 5.8% in the partially treated meningitis group (range, 0 to 27%), 2% in the proven viral meningitis group (range, 0 to 5%) and 2% in the aseptic meningitis group (range, 0 to 15%). All patients with bacterial meningitis had a LAS of > 15%, whereas all those with viral or aseptic meningitis had a score of < 15%. Although most patients with partially treated meningitis had a low LAS, several had higher scores, which may indicate bacterial infection. There was no statistical correlation between number of cells, type of cells (mononuclear or polymorphonuclear) or cerebrospinal fluid protein and glucose concentration and degree of leukocyte aggregation for the different groups. CONCLUSION: Measurement of the LAS may contribute to the immediate differential diagnosis of bacterial or viral meningitis, especially in patients with very high pleocytosis, as sometimes seen in enteroviral meningitis. It may also serve as a guide for the likelihood of bacterial infection in cases of partially treated meningitis. Additional studies are needed to confirm these observations.     

Patients with malignant meningitis presenting with neuropsychiatric manifestations

BACKGROUND: Malignant meningitis is often thought of as a late event in the course of cancer. At one time, it was thought to be rare, but it has been recognized more frequently in recent times. Clinical suspicion of malignant meningitis is prompted by neurologic symptoms and signs in patients at risk for this oncologic complication. Neuropsychiatric symptoms previously were not considered as presenting symptoms of malignant meningitis. METHODS: Three patients with cancer with no neurologic symptoms were examined for malignant meningitis based on neuropsychiatric symptoms. Cerebrospinal fluid was examined for malignant cells to confirm the diagnosis of malignant meningitis. RESULTS: The clinical presentation of malignant meningitis for three patients was neuropsychiatric. None of the patients had delirium during their initial presentation. CONCLUSIONS: It is important that clinicians recognize that psychiatric symptoms without neurologic findings may indicate malignant meningitis and that malignant meningitis needs to be included in the differential diagnosis of neuropsychiatric disorders in patients with cancer.     

Basic fibroblast growth factor in experimental and clinical bacterial meningitis

Basic fibroblast growth factor (bFGF), a neurotrophic factor in the CNS, is expressed at high levels in response to seizures or strokes. We examined the expression of bFGF during experimental bacterial meningitis and the levels of bFGF in the cerebrospinal fluid (CSF) of children with bacterial meningitis. For the experimental study, a mouse model of meningitis was established by intracranial injection of Streptococcus pneumoniae. Twenty-four hours after induced meningitis, the brains were sectioned and stained immunohistochemically for bFGF. Neutrophils and macrophages infiltrating the leptomeninges and the ventricles exhibited strong bFGF immunoreactivity. The neurons in the areas adjacent to the inflamed ventricles also showed enhanced bFGF expression. For the clinical study, we used an enzyme immunoassay to measure bFGF in CSF in 18 children with bacterial meningitis, 12 with aseptic meningitis, and 18 controls. The CSF levels of bFGF were twice as high in children with bacterial meningitis (medians 6.75-7.21 pg/mL) compared with those who had aseptic meningitis (2.9 pg/mL) or in control subjects (2.65 pg/mL, p < 0.0001, respectively). In patients with bacterial meningitis who survived, CSF bFGF decreased significantly after 24-50 h of antibiotic therapy (p < 0.0005). Patients who developed major sequelae or died had much higher levels of CSF bFGF than those without (134.9 pg/mL versus 7.38 pg/mL, p < 0.05). These findings of enhanced immunoreactivity of bFGF in experimental bacterial meningitis and an association of CSF levels of bFGF with disease severity in childhood bacterial meningitis suggest a biologic role for this neurotrophic factor in the pathophysiology of bacterial meningitis.     

Development of cochlear function in the neonate Mongolian gerbil (Meriones unguiculatus).

Studied auditory sensitivity and changes of selected structures of the external, middle, and inner ear in 31 Mongolian gerbil neonates. Data demonstrate an improvement in sensitivity to sound associated with postnatal changes in the morphology of the ear. Cochlear potentials and a concomitant reflex response to sound were observed 14 days after birth. At this state of postnatal development the organ of Corti appeared mature, the external auditory canal was open, but mesenchyme was present within the tympanic bulla. (PsycINFO Database Record (c) 2010 APA, all rights reserved)