Auditory processing control by the medial prefrontal cortex: A review of the rodent functional organisation.

Afferent inputs from the cochlea transmit auditory information to the central nervous system, where information is processed and passed up the hierarchy, ending in the auditory cortex. Through these brain pathways, spectral and temporal features of sounds are processed and sent to the cortex for perception. There are also many mechanisms in place for modulation of these inputs, with a major source of modulation being based in the medial prefrontal cortex (mPFC). Neurons of the rodent mPFC receive input from the auditory cortex and other regions such as thalamus, hippocampus and basal forebrain, allowing them to encode high-order information about sounds such as context, predictability and valence. The mPFC then exerts control over auditory perception via top-down modulation of the central auditory pathway, altering perception of and responses to sounds. The result is a higher-order control of auditory processing that produces such characteristics as deviance detection, attention, avoidance and fear conditioning. This review summarises connections between mPFC and the primary auditory pathway, responses of mPFC neurons to auditory stimuli, how mPFC outputs shape the perception of sounds, and how changes to these systems during hearing loss and tinnitus may contribute to these conditions.

Cochlear synaptopathy impairs suprathreshold tone-in-noise coding in the cochlear nucleus.

Hearing impairment without threshold elevations can occur when there is damage to high-threshold auditory nerve fibre synapses with cochlear inner hair cells. Instead, cochlear synaptopathy produces suprathreshold deficits, especially in older patients, which affect conversational speech. Given that listening in noise at suprathreshold levels presents significant challenges to the ageing population, we examined the effects of synaptopathy on tone-in-noise coding on the central recipients of auditory nerve fibres, i.e. the cochlear nucleus neurons. To induce synaptopathy, guinea pigs received a unilateral sound overexposure to the left ears. A separate group received sham exposures. At 4 weeks post-exposure, thresholds had recovered but reduced auditory brainstem response wave 1 amplitudes and auditory nerve synapse loss remained on the left side. Single-unit responses were recorded from several cell types in the ventral cochlear nucleus to pure-tone and noise stimuli. Receptive fields and rate-level functions in the presence of continuous broadband noise were examined. The synaptopathy-inducing noise exposure did not affect mean unit tone-in-noise thresholds, nor the tone-in-noise thresholds in each animal, demonstrating equivalent tone-in-noise detection thresholds to sham animals. However, synaptopathy reduced single-unit responses to suprathreshold tones in the presence of background noise, particularly in the cochlear nucleus small cells. These data demonstrate that suprathreshold tone-in-noise deficits following cochlear synaptopathy are evident in the first neural station of the auditory brain, the cochlear nucleus neurons, and provide a potential target for assessment and treatment of listening-in-noise deficits in humans. KEY POINTS: Recording from multiple central auditory neurons can determine tone-in-noise deficits in animals with quantified cochlear synapse damage. Using this technique, we found that tone-in-noise thresholds are not altered by cochlear synaptopathy, whereas coding of suprathreshold tones-in-noise is disrupted. Suprathreshold deficits occur in small cells and primary-like neurons of the cochlear nucleus. These data provide important insights into the mechanisms underlying difficulties associated with hearing in noisy environments.

Multidisciplinary management of spinal lipoma.

Spinal lipomas (congenital lipomyelomeningoceles) can cause significant aesthetic deformity of the lower spine in addition to recognised neurological problems. Surgical management consists of untethering the cord in symptomatic cases, and debulking of the lipomatous component to improve the spinal contour. However, management remains controversial. Between May 1998 and November 2002, 23 cases of lumbosacral spinal lipoma were operated on by neurosurgeons at our hospital. Of these, eight (34%) patients were subsequently referred to plastic surgery for aesthetic revision, which was performed by a combined team of plastic surgeons and neurosurgeons. In addition, three new patients had their primary surgery as a planned procedure performed by the same combined team. The purpose of this paper is to present the method and results of combined plastic surgery and neurosurgery technique in these 11 cases of spinal lipoma. Follow up ranged between 12 months and 4 years (mean 20 months). One patient had wound break down and three patients developed seroma. Two patients had cerebrospinal fluid (CSF) leakage which required re-exploration and prolonged hospitalisation. The aesthetic results were very satisfactory in 10 out of the 11 patients. The frequency of secondary referral for aesthetic revision, together with the incidence of CSF leak, underlines the importance of managing spinal lipomas in a multidisciplinary team involving neurosurgeons and plastic surgeons. This series demonstrates that aesthetic results are encouraging but decreasing the CSF leakage rate remains a challenge. Further follow up will determine the role of early combined surgery in the management of spinal lipoma.

Pattern, management and outcome of cervical spine injuries associated with head injuries in paediatric patients.

INTRODUCTION: This study examines the management and outcome of cervical spine injuries in children with head injuries, to assess the need for surgical treatment. MATERIAL AND METHODS: We performed a retrospective analysis (1995-2005) of 445 children admitted intubated and ventilated to the intensive care unit with head injuries. OUTCOME MEASURES: Frankel grade for spinal injuries and Glasgow Outcome Scale (GOS) for head injuries. RESULTS: Cervical spine injuries were detected in 11 patients (incidence 2.5%, mean age: 6.3 years, range: 21 months-15 years). The injuries were: C1/2 distraction: 2; C1/2 subluxation: 2; odontoid peg fracture with C1/2 dislocation and cord transection: 1; disruption of posterior longitudinal ligament at C2: 1; odontoid peg fracture with C2/3 distraction: 1; C2/3 subluxation: 1; C3 lamina fracture: 1; C3/4 facet fracture: 1; C6/7 fracture dislocation with cord transection: 1. One patient was managed operatively, ten patients nonoperatively, two with halo vests and eight with hard collars. There were three deaths (mortality 27%) associated with severe head injuries. At 6 months follow-up, two patients remained quadriplegic (Frankel Grade A), one of them ventilator dependent, one had residual motor function but of no practical use (Frankel Grade C), five had good spinal outcome (Frankel Grade E). Seven patients had good head injury outcomes (GOS 5), one remained disabled (GOS 3). CONCLUSION: Most children with cervical injury can be managed nonoperatively with good outcomes. Surgical management may be necessary in severe unstable injuries.

Incidence of vascular malformations in spontaneous intra-cerebral haemorrhage in children.

AIM: To assess the incidence of vascular malformations in children presenting with non-traumatic intra-cerebral haemorrhage and outline the need for radiological investigations. MATERIALS AND METHODS: Between 1993 and 2002, 26 children presented with spontaneous intra-cerebral haemorrhage at a mean age of 26 months (range 1-192 months). RESULTS: Twenty-two children had, as first treatment, surgical removal of the haematoma and any malformation found. One patient with no evidence of vascular malformation had conservative treatment, two had embolisation and one had stereotactic radiosurgery of arteriovenous malformations (AVMs). The diagnosis of vascular malformation was confirmed histologically and/or radiologically in 16 (61%) patients. Of these 16 patients, 7 were AVMs, 1 thrombosed middle cerebral artery (MCA) aneurysm, 1 cavernous angioma, 6 aggregates of abnormal vessels, 1 vein of Galen aneurysm. Pre-operatively, 12 patients had magnetic resonance imaging (MRI)/magnetic resonance angiography (MRA) and 7 were positive for vascular malformation (1 false positive) with no false negatives. Digital subtraction angiography (DSA) was performed pre-operatively in 7 patients, 4 were positive with no false negatives. There were no re-bleeds at the follow-up period. Five (19%) patients died from the haemorrhage, 7 (27%) had severe neurological deficit and 14 (54%) had no neurological deficit. Residual malformation after surgery requiring additional treatment was found in 3 (16%) patients. All patients with confirmed malformations were followed-up with DSA. CONCLUSION: MRI/MRA has high sensitivity and specificity in identifying vascular malformations in children presenting acutely with spontaneous intra-cerebral haemorrhage. This may prove useful when pre-operative DSA is not promptly available. After acute clot evacuation, there is high incidence of residual malformation and such patients should be followed-up with DSA.

Diastematomyelia in children: treatment outcome and natural history of associated syringomyelia.

OBJECTIVE: To quantify the long-term outcome of children with diastematomyelia and the implication of syringomyelia in the natural history. MATERIALS: Retrospective study of 17 children (nine girls and eight boys) with diastematomyelia operated during 1989-2004. Mean age at diagnosis was 3.4 years (range 5 days-12 years), mean follow-up was 5 years; 14 had excision of spur and cord untethering, 3 had excision of spur alone. RESULTS: The bony spur was in the lumbar region in 12 and thoracic in 5 patients. Syringomyelia was present in eight (47%), associated with bony spur between L1 and 4 (p=0.088), spina bifida occulta in ten (58.8%), and spinal lipoma in one (6%). Preoperative Necker Enfants Malades (NEM) scores were 17 in eight patients, 16 in four, 15 in three, 13 in one, and 12 in one patient. Presenting neurological deficits were motor in eight, sensory deficits in three, and anal incontinence in one patient. There was improvement of NEM scores postoperatively in five patients only, but still with residual deficit. Repeat spur excision and cord untethering was performed in three patients for neurological deterioration 1-4 years after first operation. On postoperative MRI scans syringomyelia remained unchanged in all eight patients. There were one skin infection, one transient motor deterioration, and one patient with sensory deficit after surgery. CONCLUSION: Prophylactic operations were associated with the best clinical outcome. Despite improvement, all patients with established preoperative deficit still had residual neurological deficits at their last follow-up. The associated syringomyelia remained unchanged after surgery, indicating that it does not contribute to the neurological syndrome.

Outcome of children with posterior fossa medulloblastoma: a single institution experience over the decade 1994-2003.

AIM: While the impact of radiotherapy in the management of medulloblastoma was recognised, the introduction of chemotherapy was investigated in clinical trials and shown to confer an additional advantage. We reviewed the outcome of a series of consecutive patients to assess the impact in a population-based clinical establishment. MATERIALS AND METHODS: A series of 38 children treated for medulloblastoma at Birmingham Children's Hospital between 1994 and 2003 was analysed. The effect of surgery, radiotherapy, chemotherapy and metastasis on survival was analysed. RESULTS: The overall 5-year survival rate was 61.4% for the 36 patients who had resective surgery, while 2 patients had biopsy only and died within a few months. There was no operative mortality. The incidence of hydrocephalus needing permanent shunting was higher in the first 3 years of life (p = 0.007, chi-square). The 5-year survival rate of patients with total and sub-total excision of medulloblastoma was 61.1% and 61.8%, respectively. The 5-year survival rate of patients older than 3 years was 73.4% and for patients under 3 years was 36.3% (p = 0.007, log rank). Metastases at presentation did not influence survival. All deaths occurred in the first 32 months. CONCLUSION: The contribution of chemotherapy in the improvement of the overall survival appears more evident in children younger than 3 years or presenting with metastases. The absence of significant difference in survival between patients with total or sub-total excision of medulloblastoma supports the view that total excision of medulloblastoma can be avoided when the risk for potential intra-operative damage and consequent neurological deficits is high.

Cranioplasty in children.

OBJECTIVE: The objective was to assess the outcome and complications associated with different cranioplasty implant materials in children. MATERIALS AND METHODS: A retrospective review was conducted of 28 consecutive cranioplasties carried out on 24 children between 1994 and 2001 (age range, 9 months to 15 years; minimum follow-up 18 months). The indications were: defect from previous craniectomy for trauma, tumour, infection or evacuation of haematoma (n=21), intradiploic dermoid cysts (n=2), growing fractures (n=4) and residual bony defect following craniofacial reconstruction (n=1). The materials used were: patient's craniectomised bone flap (n=16), split calvarial graft (n=8), acrylic (n=3) and titanium (n=1). All patients were assessed for bony fixation, cosmesis, wound healing and flap infection. RESULTS: There was no mortality and 18% morbidity (n=5: 3 infected flaps, 1 sterile wound dehiscence and 1 sterile wound discharge; overall infection rate 10%). Out of the 14 patients who had their own craniectomised bone flaps implanted initially, 3 became infected (2 in patients with bilateral defects) necessitating flap removal. Two of these were successfully re-implanted. No donor or recipient bone flap complications were seen in the 8 split calvarial grafts, wound discharge was seen in 1, requiring wound toilet. No complications were seen with acrylic or titanium cranioplasties. CONCLUSION: In this series, the use of the patients' own craniectomised flap had a low infection rate, and was mainly seen in patients who had bilateral flaps re-implanted soon after removal. There were no complications arising from the use of split calvarial and allograft material. Use of autologous implant material should be preferred whenever possible due to obvious resource and biological advantages, and can even be re-implanted if infected.

Percivall Pott and the miners of Cornwall.

Percivall Pott (1714-1788) was an astute and prolific mid-eighteenth century English surgeon with a strong interest in head injury. He was partial to the use of the trephine for all skull fractures and favoured early exploratory trephination when an intracranial collection could not be ruled out. If haemorrhage or abscess was beneath the dura, it was incised. Later in eighteenth century England and France, trephination fell out of favour. This was especially so in the crowded hospitals where putrid conditions were common. Surprisingly, on the remote southwestern English peninsula of Cornwall, where compound depressed skull fractures in miners were a frequent occurrence, Pott's principles prevailed unchanged. Generations of surgeons trephined early in suspected cranial fractures, without waiting for symptoms of compression or irritation. A large percentage of patients recovered. Those who died generally had diffuse injury, brain laceration, or a fractured base. The Atlantic breezes were believed beneficial to recovery. The operation of early 'preventive' trephination continued in the Cornish mining districts through the 1870s, when antiseptic methods were gradually adopted as elsewhere in England. Head injuries in miners became less common as mining reforms were introduced and head protection improved.

Cerebral abscess associated with a pulmonary arteriovenous malformation in a patient suffering from alpha thalassaemia.

We report the case of a young girl suffering from alpha thalassaemia and presenting with a brain abscess caused by a silent pulmonary arteriovenous malformation. To our knowledge this is the first such case associated with alpha thalassaemia. Diagnostic investigations and treatment options are discussed.

Spinal sagittal malalignment following surgery for primary intramedullary tumours in children.

BACKGROUND/OBJECTIVE: As prior studies analysed predictive factors for various post-laminectomy spinal deformities in mixed spinal regions, age groups or pathologies, their validity and conclusions were unclear. The objective of this study was to determine predictive factors for worsened cervical or thoracic spinal sagittal alignment following laminectomy or laminotomy for primary intramedullary spinal cord tumours in children. METHODS: In this retrospective study, patients treated between 1980 and 1998 were reviewed. Changes in spinal alignment at the last follow-up compared to the pre-operative state were studied. Factors analysed were age, pre-operative spinal alignment, procedure types (laminectomy or laminoplasty), number of laminae operated, surgery of C2 or T1 laminae, histological grade, presence of post-operative neurological deficit and post-operative radiotherapy. RESULTS: There were 27 patients. The mean age was 5.6 years (range 1.3-14.0 years), and the mean duration of follow-up was 3.7 years (range 0.075-9.9 years). In the cervical-cervicothoracic surgical group (n = 12), alignment worsened post-operatively in 3 patients. The number of laminae operated upon had a statistically significant impact on the development of post-operative kyphosis (p = 0.07). In the thoracic-thoracolumbar surgical group (n = 15), alignment worsened in 9 patients. Procedure types were statistically significantly different, with laminectomy associated with an increased risk of post-operative kyphosis (p = 0.01). All 5 patients who had spinal fusion for worsened post-operative alignment were in the thoracic-thoracolumbar group; no patients in the cervical-cervicothoracic group required spinal fusion (p = 0.047). Other predictive factors did not reach statistical significance (p > 0.05). CONCLUSIONS: Worsened spinal sagittal alignment following laminectomy or laminoplasty and the need for spinal fusion is more common in the thoracic-thoracolumbar region than in the cervical-cervicothoracic region. In the cervical-cervicothoracic region, operation on a greater number of laminae tends to increase the risk of worsened alignment. In the thoracic-thoracolumbar region, laminectomy is associated with worsened alignment, while laminoplasty reduces this risk; also, pre-operative kyphotic deformity tends to increase the risk of worsened alignment post-operatively.

Outcome of surgical treatment for subdural fluid collections in infants.

We reviewed retrospectively the management of 47 infants with subdural collections at the Birmingham Children's Hospital. Of those patients who had needle aspiration as their initial treatment 42% required some form of further treatment and 25% were complicated by infection of the subdural collection. Of those patients treated with burr hole evacuation or with observation alone, 78 and 73%, respectively, required no further procedures. However, 17% of those who had burr holes as their initial treatment developed post-operative infected collections. Of those who had subdural-peritoneal shunt as initial or subsequent treatment, none required further procedures to treat the subdural collections. No infections were noted following shunting. There was no statistically significant difference in overall clinical outcome at last follow-up between the different treatment groups. We conclude that needle aspirations should be avoided due to high infection risk, and that observation alone can be sufficient in the absence of intracranial hypertension, as the condition may be self-limiting. In cases requiring surgery, it should be borne in mind that burr hole evacuation has a higher infection risk, whereas subdural shunting has the additional need for removal of the device if the parents and surgeon decide accordingly.

Thoraco-lumbar duplication of the spine. Case report and embryology review.

OBJECT: We present a case of an asymptomatic and neurologically normal 6-year-old girl who was noted to have a gross spinal abnormality. METHODS: Neuroimaging demonstrates gross thoraco-lumbar spine duplication, which is at the severe end of the split cord malformation (SCM) group of congenital abnormalities. Despite the position of the neural structures, the clinical condition has so far not suggested that any surgical intervention is indicated, though the girl's later growth spurts may still unmask features of a tethered spinal cord. CONCLUSIONS: We present a brief review of the literature dealing with theories of embryogenesis relating to SCM, the common clinical and radiological features, and finally the surgical options available.

Spinal lipomas in children.

Spinal cord lipomas are a common cause of cord tethering that can lead to progressive neurological defects. The role of prophylactic surgery for spinal lipomas has recently been questioned. Between 1985 and 1999, 59 children underwent a total of 69 surgical procedures at the Birmingham Children's Hospital in Birmingham, UK. The spinal lipomas were classified into: 18 terminal, 17 transitional, 6 dorsal and 18 filum lipomas - including 12 who had a typical thickened filum terminale. At the first operation, 19 patients (32%) were asymptomatic, and 40 patients (68%) presented with symptoms. Surgical indications in the asymptomatic group included the presence of a dermal sinus tract or syrinx. Prophylactic surgery was undertaken in selected cases. The mean total follow-up for the group since the first surgical procedure was 61.8 months (range: 7.0-203.0 months). In the asymptomatic group, 26% of the patients had late neurological deterioration. Of the 14 patients with asymptomatic conus lipomas, 3 (21%) developed sphincter dysfunction and motor problems at long-term follow-up. In the symptomatic group, 68% improved, 20% remained unchanged, and 12% had late neurological deterioration. None of the 18 patients with symptomatic filum lipoma deteriorated postoperatively. However, 39% had bladder dysfunction, 54% had neuro-orthopaedic deformity, and only 15% returned to overall normal function at latest follow-up. Of the 27 patients with symptomatic conus lipomas, 67% improved, 15% remained stable, and 18% had late neurological deterioration. However, 74% had bladder dysfunction, 67% had neuro-orthopaedic deformity, and 45% had motor problems at long-term follow-up. Spinal lipomas can cause progressive neurological deficits irrespective of spinal untethering surgery. This study demonstrates that filum and conus lipomas have similar clinical presentation, but differ in their outcome following surgery. Filum lipomas are 'benign', for which surgery is safe and effective. Conus lipomas are more difficult to manage. When asymptomatic, our results suggest that prophylactic surgery does provide some protection from future neurological deterioration. When symptomatic, conus lipoma surgery is effective in stopping further deterioration. Improvement in neurological function can occur, but few patients return to normal overall function, and pre-existing sphincter dysfunction is not significantly altered by surgery.

The treatment of infantile hydrocephalus: "differential-pressure" or "flow-control" valves. A pilot study.

The choice of shunt valve in the treatment of hydrocephalus in children remains controversial. We embarked on a pilot study to determine the differences in outcome between differential-pressure and flow-regulating valves. Prospective data collected on 50 consecutive first-time shunt insertions, performed between June 1993 to June 1996, was analysed. Children with tumour-related hydrocephalus and Dandy-Walker malformations as well as children who had external ventricular drainage prior to definitive shunt insertion were excluded from the study. The defining event was the first complication necessitating surgery, including obstruction, over-drainage and infection. Of the 50 children (31 males), 23 had differential pressure (medium-pressure) and 27 had Delta (performance level 2) valves inserted. The mean age at shunt insertion was 26.4 months. The mean follow-up was 53.8 months. The overall cumulative shunt survival at 5 years was 58.6% for the differential pressure and 58.7% for the Delta valves. The mean shunt life was 37.1 months for the differential pressure group and 34.6 months for the Delta group. This difference was not statistically significant (P=0.72, t-test). Both valves had a similar outcome with respect to obstruction (including proximal, valve, distal). The main differences between the two valves were with respect to the incidence of over-drainage and infection. Amongst the differential pressure valves, there were 4 instances of overdrainage (3 slit-ventricle syndrome, 1 bilateral subdural collection)--all occurring within the first 36 months. The Delta valve group had only one instance of over-drainage (bilateral subdural collection). There were no infections in the differential pressure valve group, whereas 3 of the Delta valve shunts got infected, all within the first month. Whereas both shunt types seemed to have a similar overall survival, there was a relatively higher incidence of over-drainage amongst the differential pressure valves. The Delta valves, on the other hand, had higher rates of infection. Similar studies with larger numbers could suggest whether the choice of shunt type will ultimately have to be a compromise accepting one or the other complication.

Intracranial volume change in childhood.

OBJECT: The goal of this study was to construct a model of normal changes in intracranial volume occurring throughout childhood from age 7 days to 15 years. METHODS: Using the technique of segmentation on magnetic resonance images obtained in healthy children, intracranial volume was measured and plotted against age. CONCLUSIONS: Intracranial volume in the first few months of life is on average 900 cm3 in males and 600 cm3 in females. By the age of 15 years, it increases up to 1500 cm3 in males and 1300 cm3 in females, increased by factors of 1.6 and 2.1, respectively. By the time the child reaches 2 years of age, intracranial volume has reached 77% (1150 cm3 in males and 1000 cm3 in females) and, by 5 years, 90% (1350 cm3 in males and 1200 cm3 in females) of the volume observed at age 15 years. The change in intracranial volume that occurs with age is not linear, but there seems to be a segmental pattern. Three main periods can be distinguished, each lasting approximately 5 years (0-5, 5-10, and 10-15 years), during which the growth of intracranial volume is linear. Throughout childhood, males have higher intracranial volumes than females, with a similar growth pattern.