Novel Statistical Analyses to Assess Hearing Outcomes After ABI Implantation in NF2 Patients: Systematic Review and Individualized Patient Data Analysis.

BACKGROUND: Patients with neurofibromatosis type 2 develop bilateral vestibular schwannomas with progressive hearing loss. Auditory brainstem implants (ABIs) stimulate hearing in the cochlear nuclei and show promise in improving hearing. Here, we assess the impact of ABI on hearing over time by systematically reviewing the literature and re-analyzing available individual patient data. METHODS: A multidatabase search identified 3 studies with individual patient data of longitudinal hearing outcomes after ABI insertion in adults. Data were collected on hearing outcomes of different sound complexities from sound to speech using an ABI ± lip reading ability plus demographic data. Because of heterogeneity each study was analyzed separately using random effects multilevel mixed linear modeling. RESULTS: Across all 3 studies (n = 111 total) there were significant improvements in hearing over time from ABI placement (P < 0.000 in all). Improvements in comprehension of sounds, words, sentences, and speech occurred over time with ABI use + lip reading but lip reading ability did not improve over time. All categories of hearing complexity had over 50% comprehension after over 1 year of ABI use and some subsets had over 75% or near 100% comprehension. Vowel comprehension was greater than consonant, and word comprehension was greater than sentence comprehension (P < 0.0001 in both). Age and sex did not predict outcomes. CONCLUSIONS: ABIs improve hearing beyond lip reading alone, which represents baseline patient function prior to treatment, and the benefits continue to improve with time. These findings may be used to guide patient counseling regarding ABI insertion, rehabilitation course after insertion, and future studies.

Classification of spondylolytic clefts in patients with spondylolysis or isthmic spondylolisthesis using positional MRI.

Background Posterior instability is a pathologic movement occurring in the spondylolytic cleft. Purpose To present a new classification system for the evaluation of spondylolytic cleft by positional magnetic resonance imaging (MRI) and determine the prevalence of the different types. Material and Methods A total of 176 segments of the lumbar spine with spondylolysis or isthmic spondylolisthesis were examined using positional MRI. Scans were obtained in neutral sitting, flexion, and extension positions. No visible movement in the cleft was defined as type A, fluid displaced into the cleft as type BI, displacement of the flava ligaments at the level of the cleft as type BII, and intraspinal cysts arising from the spondylolytic cleft as type BIII. The movements were characterized by a radiologist and a neurosurgeon experienced in positional MRI. Clinical findings were correlated with the different types of instability. Results A high agreement was found between the two observers. In total, 131 segments were characterized as type A, six as type BI, 24 as type BII, and 10 as type BIII. In five segments, the type differed between the right and the left side. Two patients had a mixed type BI/II, another two patients had a mixed type BII/III, and one patient had a mixed type BI/III. Patients with type BII and BIII instabilities suffered more often from radicular symptoms compared to patients without any instability. Conclusion The presented classification might help to better understand and study changes encountered in the spondylolytic cleft in patients with spondylolysis and isthmic spondylolisthesis using positional MRI.

Juxtafacet cysts of the lumbar spine: a positional MRI study.

BACKGROUND/AIMS: Juxtafacet cysts (JFC) are related to facet joint degeneration. Supine MRI is routinely used to evaluate JFC. However, some JFC are missed and found only intraoperatively. The present study addresses positional MRI features and factors leading to variation in the size of JFC. METHODS: Fifty patients in whom positional MRI had been performed were investigated retrospectively and 67 distinct intraspinal or intraneuroforaminal were JFC found. Signal intensity, size of the JFC, the presence and variance of a vertebral slip and the angular movement of affected segments were assessed in supine, neutral sitting, flexion (sitting) and extension (standing). The overall movement of the spine and the lordosis angle in different positions were measured. RESULTS: JFC varied in size in segments with unstable slip and increased angular movement (variation of the angle in the affected segment in function: 13.3 degrees compared to 8.7 degrees). JFC with bright signals tended to vary in size compared to JFC with intermediate or low signal intensity (all: p < 0.001). Joint effusion and displacement of effusion lead to formation and variations in the size of JFC. JFC were most prominent in extension: 6.7 mm, less prominent in supine: 5.5 mm and in neutral sitting position: 4.6 mm (all p < 0.05). The detection rate for JFC was 97% for extension, 89% for supine and 78% for neutral sitting. CONCLUSIONS: The detection rate of JFC improves with increasing lordosis of the spine and under weight-bearing conditions, particularly when standing. Unstable slipping or increased angular movement affects the size of JFC.

Spondylolysis and spondylolisthesis: prevalence of different forms of instability and clinical implications.

STUDY DESIGN: Imaging study with an evaluation of incidences and clinical correlation. OBJECTIVE: To evaluate the incidence of 3 different types of instabilities in patients with spondylolysis or isthmic spondylolisthesis. Clinical findings are correlated with imaging findings, and the imaging findings are analyzed with regard to their clinical implications. SUMMARY OF BACKGROUND DATA: Spondylolysis and isthmic spondylolisthesis are common disorders. An unstable slip is the most well-known form of instability, but other forms also exist. However, the incidence of these instabilities and their clinical implications are yet unclear. METHODS: A total of 140 patients with 141 levels of spondylolysis identified by MRI (magnetic resonance imaging) were included in this study. Using positional MRI, the instability of the slip, an increased angular movement, and movement in the spondylolytic cleft were assessed. On the basis of clinical findings, the patients were classified as presenting with either radicular or nonradicular symptoms. The incidence of the instabilities was recorded and correlated with the incidence of radicular symptoms. RESULTS: Fifteen patients had an unstable slip (anterior instability); 35, an increased angular movement (angular instability); and 34 patients, a movement in the spondylolytic cleft (posterior instability). All forms of instability could be found together. No instability at all was found in 76 patients. Radicular symptoms were found significantly more often in patients with one or more of the described instabilities compared with patients without instability. CONCLUSION: All 3 described forms of instability are common in spondylolysis or isthmic spondylolisthesis and associated with radicular pain. This finding stresses the value of positional MRI in the evaluation of patients with spondylolysis and isthmic spondylolisthesis, especially if radicular symptoms are present.

Developmental potential of the murine embryonic stem cells transplanted into the healthy rat brain--novel insights into tumorigenesis.

Although engraftment of undifferentiated pluripotent embryonic stem cells (ESCs) into the injured central nervous system (CNS) may lead to targeted cell replacement of lost/damaged cells, sustained proliferative activity combined with uncontrolled differentiation of implanted cells presents a risk of tumor formation. As tumorigenic potential is thought to be associated with pluripotency of embryonic stem cells, pre-differentiation may circumvent this problem. Recently, it has been demonstrated that tumorigenesis occurs despite pre-differentiation if the neural precursor cells are implanted into the brain of a homologous animal (e.g., mouse to mouse). However, xenotransplantation (e.g., mouse to rat) without pre-differentiation, lead to the development of healthy neuronal cells, in absence of tumor formation, suggesting that tumor-suppressive effects of host tissue on engrafted ESCs may play a role in transplant tumorigenesis. We critically investigated tumorigenesis and possible mechanisms of anticipated tumor-suppressive effect under conditions analogous to previously published studies. Xenotransplantation of D-3 murine ESCs into uninjured adult rat brains lacking any preliminary inflammatory potential was found to lead to tumor formation in 5 out of 8 of animals within 2 weeks postimplantation. Tumor-suppressive effects, reflected by Erdo et. al could possibly be ascribed to immunomodulatory activity of macrophages scavenging the tumorigenic fraction of the implanted cells. The importance of number of engrafted cells, implantation site and immunosuppressive effects are discussed as possible variables determining tumorigenic outcome after ESC transplantation.

Interspinous implants (X Stop, Wallis, Diam) for the treatment of LSS: is there a correlation between radiological parameters and clinical outcome?

Neurogenic intermittent claudication, caused by lumbar spinal stenosis (LSS), usually occurs after the age of 50 and is one of the most common degenerative spinal diseases in the elderly. Among patients over the age of 65 with LSS, open decompression is the most frequently performed spinal operation. The recently introduced interspinous spacers are a new alternative under discussion. In this retrospective study, we reviewed medical records and radiographs of patients with LSS and NIC treated from June 2003 to June 2007. All included patients (n = 129) were treated with interspinous implants (X Stop Wallis, or Diam). Evaluations of pain, using a visual analog scale (VAS), and radiographic signs, using two-plane X-rays of the lumbar spine, were performed preoperatively (preop), postoperatively (postop) and after discharge (FU 2-3). Gender ratio (m:w) was 1.1:1. Mean age of the patients was 60.8 +/- 16.3 years. Foraminal height, foraminal width, foraminal cross-sectional area, intervertebral angle, as well as anterior and posterior disc height changed significantly (P < 0.0001) after implantation of the interspinous device. Postoperatively, symptom relief (VAS) was significant (P < 0.0001). The X Stop implant improved (in some cases significantly) the radiographic parameters of foraminal height, width, and cross-sectional area, more than the Diam and Wallis implants; however, there was no significant difference among the three regarding symptom relief. FU 1 was on average 202.3 +/- 231.9 and FU 2 527.2 +/- 377.0 days postoperatively. During FU, the radiological improvements seemed to revert toward initial values. Pain (VAS) did not increase despite this "loss of correction." There was no correlation between age and symptom improvement. There was only very weak correlation between the magnitude of radiographic improvement and the extent of pain relief (VAS). The interspinous implant did not worsen low-grade spondylolisthesis. Provided there is a strict indication and fusion is not required, implantation of an interspinous spacer is a good alternative to treat LSS. The interspinous implant offers significant, longlasting symptom control, even if initially significant radiological changes seem to revert toward the initial values ("loss of correction").

Two-year results of interspinous spacer (X-Stop) implantation in 175 patients with neurologic intermittent claudication due to lumbar spinal stenosis.

The clinical outcome of patients with symptomatic lumbar spinal stenosis (LSS) was assessed during a follow-up period of 2 years after X-Stop implantation. The X-Stop is the most commonly used interspinous distraction device in patients with neurogenic intermittent claudication due to LSS. Between 2003 and 2007, more than 1,000 patients were examined in our centre with symptoms of intermittent claudication due to spinal stenosis. Between February 2003 and June 2007, in 175 of these patients an X-Stop device was implanted in one or two levels. Patients were clinically evaluated regularly during a follow-up period of up to 4 years using the VAS (leg pain) score and the Oswestry disability index. The mean VAS (leg pain) score in these 175 patients was reduced from 61.2% preoperatively to 39.0% at the first clinical follow-up examination at 6 weeks postoperatively. The mean VAS score at 24 months postoperatively was 39.0%. Oswestry score was 32.6% preoperatively, 22.7% at 6 weeks, and 20.3% at 24 months postoperatively on average. In eight out of the implanted 175 patients, the X-Stop had to be removed and a microsurgical decompression had to be performed because of unsatisfactory effect of the interspinous distraction device. Our single-centre results indicate not only a satisfactory short-term, but also a good long-term effect during a follow-up period of 2 years. Functional MRI examinations provide helpful, positional-dependent preoperative information. More than any radiological feature, the typical clinical picture of positional-dependent claudication with a relief of symptoms during flexion is the most important factor for appropriate patient selection. The interspinous device does not replace microsurgical decompression in patients with massive stenosis and continuous claudication, but offers a save, effective and less invasive alternative in selected patients with spinal stenosis. Concerning the operative technique, a minimally invasive implantation with preservation of the interspinous ligament is appropriate. Functional (upright-) MRI examinations were able to demonstrate the positional-dependent stenosis. If available, fMRI represents the most helpful radiologic examination in assessing the outcome of interspinous spacer implantation.

Multiple cranial gunshot injuries without skull penetration.

We report on a 74 year old patient who was admitted to the Emergency Department of Cologne University after an attempt to commit suicide. Clinical examination showed no neurological deficits but two bleeding bullet holes in his head bilateral in the temporal areas initially suggesting a complete passage of a bullet through the head. The patient was able to answer questions but showed also a slight bleeding from his mouth while talking. Emergency CT showed a bullet between the internal and external lamina of the temporal bone on both sides and one bullet in the hard palate. With general anesthesia, all bullets were removed without complications, the wounds were sutured and general antibiotics were administered. The patient survived without neurological deficit and antidepressants were commenced. Examination of the gun revealed a Second World-War 7.65 mm Luger handgun with degenerated gun powder quality and humidity after 50 years storage in the patient s bedroom.

Voriconazole brain tissue levels in rhinocerebral aspergillosis in a successfully treated young woman.

Invasive aspergillosis of the central nervous system has a mortality rate exceeding 90%. We describe a 29-year-old woman with a medical history of chronic polyarthritis who developed a proven rhinocerebral Aspergillus fumigatus infection refractory to first-line treatment with liposomal amphotericin B. The patient responded successfully to salvage combination treatment with voriconazole and caspofungin. Furthermore, for the first time, voriconazole levels in an intracerebral abscess were measured in this patient undergoing voriconazole oral therapy.

Neurobehavioural deficits after severe traumatic brain injury (TBI).

OBJECTIVES: Debilitating neurobehavioural sequalae often complicate traumatic brain injury (TBI). Cognitive deficits, particularly of attention, memory, information-processing speed and problems in self-perception, are very common following severe TBI. METHOD: The Neurobehavioural Rating Scale (NRS) is a multi-dimensional clinical-based assessment instrument designed and validated to measure neurobehavioural disturbances following TBI. This study examined 41 patients who were admitted to the intensive care unit of the Department of General Neurosurgery at Cologne University Hospital after severe TBI between January 1995 and July 2003. All 27 items of the NRS were assessed 6 and 12 months post-injury. RESULTS: Subjects after severe TBI (GCS<9) showed relatively high overall scores on the NRS, reflecting a high degree of overall neurobehavioural dysfunction. NRS items did not change significantly between 6 and 12 months post-trauma for anxiety, expressive deficit, emotional withdrawal, depressive mood, hostility, suspiciousness, fatigability, hallucinatory behaviour, motor retardation, unusual thought content, liability of mood and comprehension deficit. There was a tendency of improvement for inattention, somatic concern, disorientation, guilt feelings, excitement, poor planning and articulation deficits. For conceptual disorganization, disinhibition, memory deficit, agitation, inaccurate self-appraisal, decreased initiative, blunted affect and tension even a tendency for further deterioration in the post-traumatic follow-up was detected. Changes between 6 and 12 months post-TBI were statistically significant for disorientation (improvement), inattention/reduced alertness (improvement) and excitement (deterioration). CONCLUSION: The data shows that neurobehavioural deficits after TBI do not show a general tendency to disappear over time. Some aspects related to self-appraisal, conceptual disorganization and affect may even deteriorate, thereby presenting a challenging problem for both the patients and relatives. This is in contrast to the parallel improvement of post-traumatic sensomotoric deficits.

Neural response telemetry and auditory/nonauditory sensations in 15 recipients of auditory brainstem implants.

Auditory brainstem implants (ABIs) provide a means of restoring some hearing sensations to individuals with neurofibromatosis type 2 (NF2) who are deaf after vestibular schwannoma removal. In this study, neural response telemetry (NRT) was used to record electrically evoked neuronal activity near the ABI electrode array in 15 such subjects. Our interest was to investigate whether NRT recordings from the brainstem might be useful in implanting or programming ABIs. We therefore sought relationships between postoperative NRT recordings and the sensations reported by the subjects in response to the test stimuli. However, no clear relationships among these variables were found, and it was not possible to differentiate recordings associated with auditory versus nonauditory sensations. The findings suggest that the categorization of NRT recordings used in this study is inappropriate for assisting with placement of an ABI electrode array intra-operatively or for programming the sound processor postoperatively.

The multichannel auditory brainstem implant: how many electrodes make sense?

OBJECT: Development of multichannel auditory brainstem implant (ABI) systems has been based in part on the assumption that audiological outcome can be optimized by increasing the number of available electrodes. In this paper the authors critically analyze this assumption on the basis of a retrospective clinical study performed using the Nucleus 22 ABI surface electrode array. METHODS: The perceptual performances of 61 patients with neurofibromatosis Type 2 were tested approximately 6 weeks after an eight-electrode ABI had been implanted. Of eight implanted electrodes 5.57 +/- 2.57 (mean +/- standard deviation [SD] provided auditory sensations when stimulated. Electrodes were deactivated when stimulation resulted in significant nonauditory side effects or no auditory sensation at all, and also when they failed to provide distinctive pitch sensations. The mean (+/- SD) scores for patients with ABIs were the following: sound-only consonant recognition, 20.4 +/- 14.3 (range 0-65%); vowel recognition, 28.8 +/- 18% (range 0-67%); Monosyllable Trochee Spondee (MTS) word recognition 41.1 +/- 25.3% (range 0-100%); and sentence recognition, 5.3 +/- 11.4% (range 0-64%). Performance in patients in whom between one and three electrodes provided auditory sensation was significantly poorer than that in patients with between four and eight functional electrodes in the vowel, MTS word, and City University of New York (CUNY) sentence recognition tests. The correlation between performance and electrode number did not reach the 0.05 level of significance with respect to the sound effect, consonant, and MTS stress-pattern recognition tests, probably because a satisfactory performance in these tests can be obtained only with temporal cues, that is, without any information about the frequency of the sounds. In the MTS word and the CUNY sentence recognition tests, performance was optimal in the patients with eight functional electrodes. Although all top performers had more than three functional auditory electrodes, no further improvement (asymptotic performance) was seen in those with five or more active electrodes in the consonant, vowel, and sound effect recognition tests. CONCLUSIONS: A minimum of three spectral channels, programmed in the appropriate individual tonotopic order seem to be required for satisfactory speech recognition in most patients with ABI. Due to the limited access to the tonotopic frequency gradient of the cochlear nucleus with surface stimulation, patients with ABI do not receive a wide range of spectral cues (frequency information) with multielectrode (> 5) surface arrays.

Multichannel auditory brainstem implant: update on performance in 61 patients.

OBJECT: Neurofibromatosis Type 2 (NF2) has typically resulted in deafness after surgical removal of bilateral vestibular schwannomas (VSs). Cochlear implants are generally ineffective for this kind of deafness because of the loss of continuity in the auditory nerve after tumor removal. The first auditory brainstem implant (ABI) in such a patient was performed in 1979 at the House Ear Institute, and this individual continues to benefit from electrical stimulation of the cochlear nucleus complex. In 1992, an advanced multichannel ABI was developed and a series of patients with NF2 received this implant to study the safety and efficacy of the device. METHODS: At the time of first- or second-side VS removal, patients received an eight-electrode array applied to the surface of the cochlear nucleus within the confines of the lateral recess of the fourth ventricle. The device was activated approximately 6 weeks after implantation. and patients were tested every 3 months for the 1st year after the initial stimulation, and annually thereafter. The protocol included a comprehensive battery of psychophysical and speech perception tests. CONCLUSIONS: The multichannel ABI proved to be effective and safe in providing useful auditory sensations in most patients with NF2. The ABI improved patients' ability to communicate compared with the lipreading-only condition, it allowed the detection and recognition of many environmental sounds, and in some cases it provided significant ability to understand speech by using just the sound from the ABI (with no lipreading cues). Its performance in most patients has continued to improve for up to 8 years after implantation.