Cognitive impairment and quality of life in long-term survivors of malignant brain tumors

Thirtysix long-term survivors following the treatment of a malignant supratentorial brain tumor were examined for cognitive functions and global level of autonomy. Eighteen patients were symptom-free (SF) and 18 had clinical and neuroradiological recurrence (RE). The control group included 30 healthy subjects. All subjects underwent a neuropsychological battery for general and specific cognitive functions. The level of autonomy was assessed by means of the Karnofsky Performance Scale (KPS) for oncological patients. SF patients showed less impairment than RE patients both at the tests, as well as on the KPS. The cognitive deficits were subclinical in most SF patients, the tests for attention, memory and word fluency being the most sensitive in detecting subtle dysfunctions. The association between tumor location and specific cognitive deficits was inconstant in both patient groups. The results suggest that even subtle cognitive deficits can prevent SF long-term survivors from returning to premorbid autonomy and occupations, and that neuropsychological tests may be used as complementary routine indicators of their quality of life. Furthermore, our data show that, in selected patients, combined treatments and therapeutic insistence do not necessarily have the same deleterious effects.     

Cytochemical and biochemical studies on adenylate cyclase activity in preneoplastic and neoplastic liver tissue and cultured liver cells

OBJECTIVE: To assess the accuracy of: 1) distortion product otoacoustic emission (DPOAE) measures for the identification of frequencies at which auditory sensitivity is normal or near normal; and 2) click and nonmasked tone burst-evoked auditory brain stem response (ABR) thresholds for behavioral threshold estimation for children with sensorineural hearing loss characterized by islands of normal sensitivity. DESIGN: DPOAEs and ABRs were recorded from five hearing-impaired and eight normal-hearing pediatric ears. The accuracy with which DPOAEs permitted identification of frequencies at which elevated hearing thresholds were present was examined. ABR and pure-tone threshold differences for the impaired ears were calculated. RESULTS: For three of the five hearing-impaired ears, significant impairments would have been missed based on click-evoked ABR thresholds. One of those hearing-impaired ears provided an essentially normal 500 Hz tone burst-evoked ABR threshold as well. Four of the hearing-impaired ears provided a 500 Hz tone burst-evoked ABR threshold within 10 dB of the respective pure-tone threshold. However, click-evoked ABR and 500 Hz tone burst-evoked ABR threshold data did not adequately delineate the hearing loss configuration for hearing aid frequency response selection. DPOAEs were present at three out of four frequencies from 1000 to 4000 Hz at which sensitivity was normal or near normal (< or =25 dB HL) and absent at 10 out of 11 frequencies at which sensitivity was impaired. The use of DPOAEs to identify frequencies at which sensitivity was normal and the use of tone burst ABR thresholds at frequencies where DPOAEs were absent provided a better estimate of these pure-tone audiograms than was provided by click-evoked and 500 Hz tone burst-evoked ABR thresholds.     

Neuro-otological function in X-linked hearing loss: a multipedigree assessment and correlation with other clinical parameters

Auditory and vestibular investigations were carried out in 19 affected men and 13 obligate female carriers of 7 pedigrees with nonsyndromic hearing loss segregating as an X-linked trait. In addition, high resolution computerised tomographic scanning was carried out in 24 affected males and 12 obligate female carriers. The neuro-otological results confirm that non syndromic X-linked hearing loss is a clinically heterogeneous condition, but radiological assessment of the cochlea revealed two distinct groups: a normal group, and an abnormal group characterised by a bulbous internal auditory meatus, a dilated facial nerve canal and incomplete separation of the basal coil of the cochlea from the internal auditory meatus. Within a given pedigree there was marked consistency of the presence or absence of the CT scan abnormality in the affected males. One third of the obligate female carriers of the radiologically abnormal pedigrees were shown to have a similar abnormal finding, but as two thirds were normal, radiological examination did not predict carrier status. In the affected men, pure tone audiometric data did not correlate with the radiological abnormality, whereas vestibular function was strikingly correlated, being normal in all but one case in pedigrees with normal radiology and absent, or grossly impaired, in the pedigrees with abnormal radiology. Neuro-otological abnormalities were documented in approximately two thirds of the obligate female carriers, but were insufficiently frequent in occurrence or specific in type to be of predictive value.     

Mismatch negativity in the neurophysiologic/behavioral evaluation of auditory processing deficits: a case study

The subject of this case report is an 18-year-old woman with grossly abnormal auditory brain stem response (ABR), normal peripheral hearing, and specific behavioral auditory processing deficits. Auditory middle latency responses (MLRs) and cortical potentials N1, P2, and P300 were intact. The mismatch negativity (MMN) was normal in response to certain synthesized speech stimuli and impaired to others--consistent with her behavioral discrimination of these stimuli. Behavioral tests of auditory processing were consistent with auditory brain stem dysfunction. A neuropsychological evaluation revealed normal intellectual and academic performance. The subject was in her first year of college at the time of the evaluation. This case study is important because: (1) Although there have been several reports of absent/abnormal ABR with preserved peripheral hearing and deficits in auditory processing, little is known about the specific nature of the auditory deficits experienced by these individuals. Such information may be valuable to the clinical management of patients with this constellation of findings. (2) Of interest is the information that the mismatch negativity (MMN) cortical event-related potential can bring to the evaluation of patients with auditory processing deficits. The MMN reflects central auditory processing of small acoustic differences and may provide an objective measure of auditory discrimination. (3) From a theorectical standpoint, a patient with neural deficits affecting specific components of the auditory pathway provides insight into the relationship between evoked potentials and physiological mechanisms of auditory processing. How do various components of the auditory pathway contribute to speech discrimination? How might evoked potentials reflect the processes underlying the neural coding of specific features of speech stimuli such as timing and spectral cues?     

Intensity and frequency discrimination monitored by evoked response audiometry: clinical application

Delta 1 and delta f repetitive stimuli superimposed on continuous 0.5-, 1- and 4-kHz carrier tones were administered to 20 normally hearing persons, 8 adults with sensorineural hearing loss, 10 adults with conductive hearing loss and 22 children subjected to evoked response audiometry (ERA) for assessment of hearing acuity. The intensity modulation depth ranged from + 1 to 10 dB. In the subjects with normal hearing and in the adult patients, three carrier tone levels were used whenever possible: 20, 40, and 60 dB SL. The frequency modulation depth ranged from -1 to -10% of the carrier tone frequency. The same levels for the carrier tone were used: 20, 40, and 60 dB SL. With a carrier tone level of 20 dB SL, a clear-cut vertex response was noted in 80% of the tests carried out in the normal adults with 5-dB delta i stimuli and with delta f stimuli of -3 to -5% in magnitude; the same figures are valid for the patients with sensorineural and conductive hearing loss. The patients with sensorineural hearing loss showed a tendency to give vertex responses with lower delta i stimuli than subjects with normal hearing. However, this difference was not statistically significant. According to our results, the children tested can be roughly divided into two groups, the first including subjects with responses to delta i stimuli of +5 and +10 dB and delta f stimuli of -5% and -10%; the second group including subjects with no clear-cut responses to these stimuli.     

Where the imaginal appears real: a positron emission tomography study of auditory hallucinations

An auditory hallucination shares with imaginal hearing the property of being self-generated and with real hearing the experience of the stimulus being an external one. To investigate where in the brain an auditory event is "tagged" as originating from the external world, we used positron emission tomography to identify neural sites activated by both real hearing and hallucinations but not by imaginal hearing. Regional cerebral blood flow was measured during hearing, imagining, and hallucinating in eight healthy, highly hypnotizable male subjects prescreened for their ability to hallucinate under hypnosis (hallucinators). Control subjects were six highly hypnotizable male volunteers who lacked the ability to hallucinate under hypnosis (nonhallucinators). A region in the right anterior cingulate (Brodmann area 32) was activated in the group of hallucinators when they heard an auditory stimulus and when they hallucinated hearing it but not when they merely imagined hearing it. The same experimental conditions did not yield this activation in the group of nonhallucinators. Inappropriate activation of the right anterior cingulate may lead self-generated thoughts to be experienced as external, producing spontaneous auditory hallucinations.     

Bilateral loss of vestibular function: clinical findings in 53 patients

The clinical presentations and aetiologies of a series of 53 cases of bilateral vestibular failure (BVF) seen by the authors over a decade were evaluated by retrospective review of the medical records. Thirty-nine per cent of patients had associated neurological disease; 13% had a progressive cerebellar syndrome with disabling gait ataxia, abnormal eye movements and cerebellar atrophy on neuro-imaging. BVF was usually unsuspected. Nine per cent had cranial or peripheral neuropathies and in this group there was no abnormality of brain stem/cerebellar oculomotor function, but hearing loss was common. Eleven per cent revealed BVF and hearing loss secondary to meningitis, and 6% had other neurological disorders. Idiopathic BVF was found in 21% of cases, characterised by paroxysmal vertigo and/or oscillopsia, but no abnormal clinical signs. Gentamicin ototoxicity accounted for a further 17%, while autoimmune disease was present in 9% of patients. Otological or neoplastic disease was diagnosed in the remaining 13% of patients. It was concluded that neurological, audiological and ocular motor assessments allow the probable cause of BVF to be defined in approximately 80% of cases. A group of BVF related to autoimmune pathologies is reported for the first time, indicating the need for immunological screening. Idiopathic BVF may present with only minor visual or vestibular symptoms, while in patients with cerebellar degeneration, BVF may be unsuspected and, thus, underdiagnosed.     

The vestibulo-ocular reflex in pupils at a Dutch school for the hearing impaired; findings relating to acquired causes

The vestibulo-ocular reflex was evaluated with caloric tests and velocity step (VS) tests in 121 pupils at a school for the hearing-impaired. Vestibular impairment was found in a total of 50 pupils (41%). It was found in 17 out of the 33 (52%) pupils with acquired causes of hearing impairment and significantly more often in pupils with a pure tone hearing threshold of more than 90 dB than in those with a lower threshold. In the group with prenatal causes, 5 out of 8 rubella cases showed vestibular impairment. Four of these cases had impaired VS responses and normal caloric responses. The high proportion of vestibular impairment in the group with postnatal causes was due to 5 cases with meningitis, all of whom showed caloric weakness. Kernicterus was significantly associated with vestibular hyperreactivity (5 cases out of 7), presumably due to a central dysfunction.     

Analysis of evoked otoacoustic emissions in patients with high frequency cochlear hearing loss

Evoked otoacoustic emissions (EOAE) and auditory brainstem evoked response (ABR) were tested in patients with high frequency cochlear hearing loss and subjects with normal hearing. Results showed that: 1. In the normal group, the main component of EOAE varied between 0.5-5kHz. 2. There was a close correlation between the pure-tone audiogram figure and EOAE spectrum. 3. The I/O function curves of EOAE displayed non-linear characteristics and a trend of saturation with higher stimulus levels in the normal group. In the patient group the growth rates of EOAE and ABR were remarkably higher than those in the normal group with high stimulus levels. It suggests that the abnormal EOAE are probably relevant to the recruitment phenomenon in cochlear hearing loss.     

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.     

Unraveling the mystery of cognitive changes in old age: correlation of neuropsychological evaluation with neuropathological findings in the extreme old

In order to understand what cognitive changes can be expected with aging versus those caused by disease, the New England Centenarian Study examined correlations between neuropsychological evaluation and neuropathological studies of centenarian subjects. Sixty-nine subjects were administered an extensive neuropsychological test battery designed for centenarians. Six brain donors from this group have subsequently died, and neuropathological studies of their brains have been performed to determine the presence of Alzheimer's disease (AD) and other pathological states. Of these six centenarians, three subjects had Clinical Dementia Rating scores of 0 and no dementia on neuropsychological testing, and subsequent neuropathology showed very limited AD changes. In fact, despite a range of neuropsychological findings, none of the subjects in this series met neuropathological criteria for a diagnosis of definite AD. Findings suggest that dementia is not inevitable with aging and that dementia in this age group is surprisingly often not attributable to AD.     

Prevention of hearing loss in experimental pneumococcal meningitis by administration of dexamethasone and ketorolac

Pneumococcal meningitis remains a significant cause of morbidity, particularly sensorineural hearing loss. Recent literature has suggested that a vigorous host immune response to Streptococcus [corrected] pneumoniae is responsible for much of the neurologic sequelae, including deafness, after bacterial meningitis. This study used a rabbit model of hearing loss in experimental pneumococcal meningitis to evaluate the therapeutic effect of two anti-inflammatory agents, dexamethasone and ketorolac, coadministered with ampicillin. Both adjunctive drugs minimized or prevented sensorineural hearing loss compared with placebo. Dexamethasone, administered 10 min before ampicillin, was particularly effective in minimizing mean hearing threshold change compared with placebo for both clicks (dexamethasone: 6.7-dB sound pressure level [SPL] vs. placebo: 33. 4-dB SPL, P=.0078) and 10-kHz tone bursts (dexamethasone: 8.4-dB SPL vs. placebo: 53.4-dB SPL, P=.0003). These findings support the beneficial role of anti-inflammatory agents in reducing the incidence of hearing loss from pneumococcal meningitis, especially if therapy is instituted early in the course of infection.     

Auditory information processing during acute insulin-induced hypoglycaemia in non-diabetic human subjects

Acute insulin-induced hypoglycaemia impairs performance on tests of general mental ability in humans. It is recognized that different brain functions vary in their sensitivity to neuroglycopenia, but little is known about the effects of neuroglycopenia on specific brain processes. The effect of controlled hypoglycaemia on two aspects of auditory information processing (auditory temporal processing and simple auditory processing) was examined in a homogeneous group of 20 healthy non-diabetic human subjects. Auditory temporal processing (temporal order discrimination) and simple auditory processing (pitch discrimination, single-tone duration and single-tone loudness discrimination) tests were part of the Test of Basic Auditory Capabilities (TBAC). Two tests of general cognitive performance (Digit Symbol Substitution and Trail Making B) were included to provide a measure of general brain functioning during hypoglycaemia. Hypoglycaemia lead to a significant deterioration in auditory temporal processing (P < 0.01), and a deterioration in one of three tasks of simple auditory processing (discrimination of single-tone loudness, P < 0.05). Significant disruptions also occurred in both tests of general brain functioning. These results are congruent with other studies in human subjects, showing a disruptive effect of hypoglycaemia on visual information processing when examined under conditions of limited perceptual time, and they provide further evidence of the importance of sensory processing speed in basic perceptual and cognitive functions. The disruptive effect of moderate insulin-induced hypoglycaemia on auditory perception may have implications for insulin-treated diabetic humans exposed to this metabolic stress, because of the importance of hearing in everyday life.     

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.     

Auditory deprivation and recovery in adults with asymmetric sensorineural hearing impairment

The purpose of this investigation was to investigate (1) whether auditory deprivation effects are present in the poorer ears of adults with asymmetric sensorineural hearing impairment and (2) whether, if such effects are present, they can be reversed by amplification. Subjects were 16 males with asymmetric sensorineural hearing impairment, 8 of whom had never been aided, 6 of whom were aided monaurally at the initial test, and 2 of whom were unaided at the initial test but aided monaurally later on. Data were obtained from a retrospective review of records. The initial and retest (2-13 years post initial test) suprathreshold speech-recognition scores for 50-word, taped lists of the CID W-22 PB words were analyzed. The results revealed a significant difference between the initial and retest mean suprathreshold speech-recognition scores for the poorer ears of the unaided subjects. The results also revealed no significant change from the initial test to retest in six of the aided ears and significant improvement from the initial test to retest in the two of the aided ears. The findings are discussed with reference to the theory of auditory deprivation and recovery from auditory deprivation by amplification.     

Pediatric and psychiatric comorbidity. Part I: The future of consultation-liaison psychiatry

This study was conducted to investigate the influence of high-frequency aircraft noise on the function of the auditory system of school-age children. A total of 228 students attending a school near an airport (school A) and 151 students attending a school far from an airport (school B) were analyzed. Audiometry and brainstem auditory evoked potential (BAEP) detection were performed in all subjects to evaluate cochlear and retrocochlear function. The results of audiometry indicated that hearing ability was significantly worse in the children of school A, which was located under the flight paths. The values of pure tone average, high pure tone average, and threshold at 4 kHz were all higher in children who were frequently exposed to aircraft noise. There was no consistent difference in BAEP latencies between the two schools. These results indicate that central transmission is not affected in children who have been exposed to aircraft noise for several years. The results of the present study showed a significant association between aircraft noise exposure and prevalence of noise-induced hearing loss. Although damage to peripheral cochlear organs was confirmed in school-age children, involvement of the central auditory pathway could not be verified.     

Audio-vestibular manifestations of Chiari malformation and outcome of surgical decompression: a case report

Sensorineural hearing loss, tinnitus, dizziness and ataxia are recognised symptoms associated with Chiari malformations but they are rarely the presenting complaints. Patients with such symptoms are frequently referred to otolaryngologists and audiological physicians. We report a case of a 13-year-old girl who presented complaining of tinnitus and impaired hearing, and was subsequently diagnosed as having a type I Chiari malformation. Pure tone audiogram showed a mild hearing impairment on the left side and the speech audiogram was normal. Auditory brain stem responses and the electronystagmography were abnormal. The patient underwent posterior fossa decompression following which her tinnitus disappeared, the hearing problem recovered and some of the abnormal electrophysiological parameters were corrected.     

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.     

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.     

The electrophysiological indices of the state of the different sections of the auditory analyzer in persons with a normal voice and with functional voice disorders]

Individuals with normal voice and patients with voice functional impairments undergone electrophysiological investigation of various parts of the hearing system, using tone audiometry, including the extended frequency band (10, 12, 14 and 16 kHz), as well as short- and long-latency acoustic evoked potentials (SLAEP and LLAEP). It was found out, that individuals with voice functional impairments had all of their hearing system's parts impaired to various extent, with more marked impairments in the central, rather than in the peripheral part of the hearing system. It was shown, that hearing at 4-8 kHz, as well as with the extended frequency band, especially at 14-16 kHz, time patterns of acoustic evoked potentials (latencies of waves III and V of SLAEP, the interpeak interval I-V, as well as the latency periods of the LLAEP components P2 and N2) could be useful in professional selection of individuals of voice and speech professions and for solving labor expertise matters. Of those individuals with normal voice but systematic vocal stress, 17.5% had impaired hearing at 14 and 16 kHz, as well as significant latency prolongation of the LLAEP wave N2 with tone stimulation at 1 and 4 kHz. Apparently, individuals of voice and speech professions should be referred to as the "risk" group. It may well be, that extended band audiometry and acoustic evoked potentials time patterns could be useful in determining the thresholds between the normality and pathology in voice dysfunctions.