A snapshot of European neurosurgery December 2019 vs. March 2020: just before and during the Covid-19 pandemic.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or Covid-19), which began as an epidemic in China and spread globally as a pandemic, has necessitated resource management to meet emergency needs of Covid-19 patients and other emergent cases. We have conducted a survey to analyze caseload and measures to adapt indications for a perception of crisis. METHODS: We constructed a questionnaire to survey a snapshot of neurosurgical activity, resources, and indications during 1 week with usual activity in December 2019 and 1 week during SARS-CoV-2 pandemic in March 2020. The questionnaire was sent to 34 neurosurgical departments in Europe; 25 departments returned responses within 5 days. RESULTS: We found unexpectedly large differences in resources and indications already before the pandemic. Differences were also large in how much practice and resources changed during the pandemic. Neurosurgical beds and neuro-intensive care beds were significantly decreased from December 2019 to March 2020. The utilization of resources decreased via less demand for care of brain injuries and subarachnoid hemorrhage, postponing surgery and changed surgical indications as a method of rationing resources. Twenty departments (80%) reduced activity extensively, and the same proportion stated that they were no longer able to provide care according to legitimate medical needs. CONCLUSION: Neurosurgical centers responded swiftly and effectively to a sudden decrease of neurosurgical capacity due to relocation of resources to pandemic care. The pandemic led to rationing of neurosurgical care in 80% of responding centers. We saw a relation between resources before the pandemic and ability to uphold neurosurgical services. The observation of extensive differences of available beds provided an opportunity to show how resources that had been restricted already under normal conditions translated to rationing of care that may not be acceptable to the public of seemingly affluent European countries.

Molecular characterisation of SMARCB1 and NF2 in familial and sporadic schwannomatosis.

BACKGROUND: Schwannomatosis is a rare condition characterised by multiple schwannomas and lack of involvement of the vestibular nerve. A recent report identified bi-allelic mutations in the SMARCB1/INI1 gene in a single family with schwannomatosis. We aimed to establish the contribution of the SMARCB1 and the NF2 genes to sporadic and familial schwannomatosis in our cohort. METHODS: We performed DNA sequence and dosage analysis of SMARCB1 and NF2 in 28 sporadic cases and 15 families with schwannomatosis. RESULTS: We identified germline mutations in SMARCB1 in 5 of 15 (33.3%) families with schwannomatosis and 2 of 28 (7.1%) individuals with sporadic schwannomatosis. In all individuals with a germline mutation in SMARCB1 in whom tumour tissue was available, we detected a second hit with loss of SMARCB1. In addition, in all affected individuals with SMARCB1 mutations and available tumour tissue, we detected bi-allelic somatic inactivation of the NF2 gene. SMARCB1 mutations were associated with a higher number of spinal tumours in patients with a positive family history (p = 0.004). CONCLUSION: In contrast to the recent report where no NF2 mutations were identified in a schwannomatosis family with SMARCB1 mutations, in our cohort, a four hit model with mutations in both SMARCB1 and NF2 define a subset of patients with schwannomatosis.

The burden of motorcycle-related neuro-trauma in Ireland and associated helmet usage.

Motorcycles represent less than 2% of the licensed vehicles but motorcyclists account for 12% of road deaths in Ireland. The British Road Safety Authority has introduced the Sharp programme, which hopes to save 50 lives in the U.K. each year alone by helping riders to choose the best-fitting and safest helmets. We evaluated the pattern of head injuries sustained by motorcyclists referred to the two neurosurgical centres Beaumont Hospital and Cork University Hospital in Ireland and ascertained if the new SHARP guidelines could be of benefit in reducing the burden of motorcycle related neurotrauma and disability in Ireland. Despite Ireland having mandatory helmet laws almost a quarter of our motorcyclists with traumatic brain injury were unhelmeted. A significant reduction in mortality and morbidity is predicted if all motorcyclists in Ireland were to wear helmets that satisfied the SHARP criteria.

Lateral mass screw fixation of complex spine cases: a prospective clinical study.

The purpose of this paper was to report our experience with lateral mass screw fixation when used in a variety of complex cervical pathologies. A prospective observational study was undertaken of all patients who underwent lateral mass screw fixation for complex spinal pathology. There were 59 patients. Pathology included cervical spondylosis with deformity 58%, rheumatoid arthritis 19%, tumours 15%, multiple level trauma 8%. The median follow-up time was 23 months. The patient's myelopathy scores improved in 64% of patients. 79% reported an improvement in their neck disability scores. 73% had improvement in their visual analogue pain score. Sixty-one per cent had preoperative high signal change on T2WI MRI. Sixty per cent had loss of normal cervical lordosis on presentation or were kyphotic. Sixty-four per cent of patients had grade 3 compression on MRI (Singh). Postoperative alignment was maintained in all cases. No late kyphotic deformity occurred. Lateral mass screw fixation can be used effectively and safely for different cervical spine pathologies with good functional and radiological outcome.

Evaluation of misonidazole peripheral neurotoxicity in rats by analysis of nerve trains evoked response.

The clinical use of misonidazole and other nitroimidazole radiosensitizing agents is limited by the peripheral and central neurotoxicity that is produced in animals and humans. In a blinded study, rats treated with misonidazole at either 100 mg/kg or 300 mg/kg, 5 days/week for 3 weeks, were evaluated for peripheral neurotoxicity using nerve trains evoked responses. Only one rat treated at a dose of 100 mg/kg developed symptoms and signs of neurotoxicity, while all rats treated at 300 mg/kg developed these signs and symptoms. Nerve trains analysis made possible a diagnosis of neurotoxicity before overt clinical signs appeared. This test is non-invasive and may be useful for evaluating patients receiving nitroimidazole radiosensitizers as part of a radiation therapy regimen.

Effect of age on ocular microtremor activity.

BACKGROUND: Ocular microtremor (OMT) is a high-frequency tremor of the eyes. It is present in all individuals and is related to brainstem activity. The OMT signal appears as an irregular oscillatory movement with intermittent burst-like components. The clinical interest in OMT has centered on its use in the assessment of the comatose patient, with broad agreement among authors of its prognostic value. The purpose of this study was to examine the changes in OMT activity related to aging. METHODS: OMT was recorded from 72 normal healthy subjects using the piezoelectric strain gauge technique. The subjects ranged in age from 21 to 88 years (54.22 +/- 20.43 years, mean +/- SD). RESULTS: Our results show that the overall frequency and frequency content of the bursts falls with age (p < .002 and p < .001, respectively). There is a highly significant drop in all three frequency parameters of OMT (p < .0001) in subjects older than 60 years of age. CONCLUSIONS: These results suggest that different values of normality should operate for subjects over 60 years of age when considering the clinical application of OMT.

An antisense oligonucleotide to brain-derived neurotrophic factor delays postural compensation following unilateral labyrinthectomy in guinea pig.

An antisense oligonucleotide to brain-derived neurotrophic factor (BDNF) was delivered by osmotic mini-pump at a 1 mM concentration via a cannula into the ipsilateral vestibular nucleus complex from 15 to 56h following unilateral labyrinthectomy in guinea pigs. Compared with the control groups, vestibular compensation of roll head tilt was significantly delayed (p < 0.05), while compensation of spontaneous nystagmus and yaw head tilt was unaffected. These results suggest that neurotrophins such as BDNF may be involved in specific aspects of the vestibular compensation process.

Diagnosis of acute nerve compression in the cat with high frequency nerve trains evoked responses.

High frequency nerve trains were evaluated from above and below the site of compression before, during, and after acute compression of the sciatic nerves of six adult cats. Acute nerve compression reduced the ability of axons to conduct high frequency impulse trains: the longer the compression, the lower the frequency of impulses that could be conducted through the region of compression without a decrement in latency and amplitude. Possible mechanisms for alterations of nerve trains and the possible clinical and experimental use of nerve trains analysis are discussed.

Lipoprotein (a): a potential biological marker for unruptured intracranial aneurysms.

OBJECTIVE: The diagnosis and treatment of intracranial aneurysms (IAs) prior to rupture reduces the high morbidity and mortality associated with their occurrence. Elevated serum lipoprotein (a) [Lp(a)] level, an independent risk factor for atherogenesis, has been demonstrated in sporadic IA disease (1). The purpose of this study was to assess the degree of correlation between elevated Lp(a) levels and the occurrence of IAs in asymptomatic first degree relatives of index cases from three families exhibiting a familial tendency towards IA development. METHODS: 25 family members and 41 healthy controls were screened by random serum Lp(a) sampling. All family members received 4-vessel cerebral angiography. RESULTS: Eleven family members were found on angiography to harbour asymptomatic aneurysms and all were successfully treated by surgery. Of these 11, ten had significantly raised serum Lp(a) levels (> 30 mg%). Fourteen family members had negative angiograms. Eight of this latter group, mean age 43.6 +/- 3.8 years, had serum Lp(a) levels above the normal range. Mean Lp(a) levels were 53.7 +/- 1.2 mg% in subjects with aneurysms compared with 22.1 +/- 1.45 mg% in subjects without demonstrable aneurysms and 10.5 +/- 0.48 mg% in the control population. CONCLUSION: The prevalence of elevated Lp(a) levels in these families and the high degree of association of raised Lp(a) levels with the presence of IAs in several family members warrants follow up of angiographically negative young subjects. We require a case-control study to establish whether particular polymorphisms at the apoprotein (a) gene level are associated with the occurrence of IAs in these families.

Comparison of the brain tissue response in rats to injury by argon and carbon dioxide lasers.

This study compares the acute and chronic response of brain tissue to injury by equal power density, focused argon (Ar) and carbon dioxide (CO2) laser beams. A cortical incision from 0.2-second laser pulses of 12.5 X 10(3) W/cm2 power density was made in the exposed cortex of 32 rats using either the CO2 or the Ar laser. The brains were examined at intervals from 1/2 hour to 1 month after injury. Histologically, all brain incisions were sharply demarcated hemispheroidal defects with a vaporized center bordered by a zone of coagulation necrosis surrounded by edema. The laser incisions were found to be of equal depth (less than 1 mm). The average cortical surface diameter of the CO2 laser incision was 0.86 mm for a focused beam spot size 0.45 mm in diameter, compared with 0.65 mm with the Ar laser, which had a focused beam spot size 0.15 mm in diameter. In both incisions, some delayed depth effect was observed. A progression of the tissue necrosis by approximately 17% was observed during the first 24 hours after injury. During the first 4 hours after injury, the Evans blue blood-brain barrier defect (EBBD) surrounding the cortical incisions averaged 5.80 mm2 for the CO2 incision and 0.888 mm2 for the Ar incision. In both types of brain incision, the EBBD appeared to resolve by 24 hours after injury. At 1 month after injury, a core of coagulation necrosis surrounded by mild fibrillary gliosis was observed. At the power density and focused beam spot sizes used, there was no significant difference in the overall brain tissue response to Ar and CO2 laser lesions.

Effect of microsurgical and carbon dioxide and argon laser resection on recurrence of the intracerebral 9L rat gliosarcoma.

The intracerebral 9L rat brain tumor was resected from 38 rats with the use of standard microsurgical techniques, the carbon dioxide laser, or the argon laser. The extent of resection was evaluated by histological examination, and the effect on survival of the three methods was compared. All three methods achieved histologically verifiable gross total resection, and tumor recurrence after resection by all three methods occurred at the same rate.

Elevated levels of lipoprotein (a) in association with cerebrovascular saccular aneurysmal disease.

The relationship between cerebrovascular aneurysmal disease and atherosclerosis remains unclear. Elevated serum levels of lipoprotein (a) (Lp[a]), are an independent risk factor for atherosclerosis. We measured serum Lp(a) levels in 50 patients who had angiographically proven saccular aneurysmal disease and who were free of clinically significant atheromatous disease (as judged by their medical histories and the results of physical examination, electrocardiography, and carotid angiography). The Lp(a) serum levels in these patients were compared with the Lp(a) serum levels in a group of 42 normal healthy controls. Serum Lp(a) levels in the patients was 20.1 +/- 0.42 mg/dl (median +/- standard error); however, median serum Lp(a) in the control subjects was 10.8 +/- 0.47 mg/dl (P < 0.01). Among females, the difference in serum Lp(a) levels was significant; the levels were 22.2 +/- 0.6 for female patients (n = 29) and 9.5 +/- 0.53 in female control subjects (n = 26) (P < 0.005). The most significant difference (P < 0.002) was seen in females < 50 years old (14 patients, 10 control subjects). No significant differences were seen in the Lp(a) serum levels between 21 male patients and 16 male control subjects. Lp(a) levels above the threshold level (30 mg/dl) were found in 20 patients and 7 control subjects (chi 2 = 5.99, P < 0.02); 12 female patients and 3 female control subjects (chi 2 = 6.16, P < 0.02; 8 male patients and 4 male control subjects (this difference was not significant). These results indicate either that cerebrovascular aneurysmal disease and subclinical atherosclerosis are related or that Lp(a) is a risk factor for vasculopathies other than atheroma.

Dominant frequency content of ocular microtremor from normal subjects.

Ocular microtremor (OMT) is a high frequency tremor of the eyes present during fixation and probably related to brainstem activity (Coakley, D. (1983). Minute eye movement and brain stem function. CRC Press, FL.). Published observations on the frequency of OMT have varied widely. Ocular microtremor was recorded in 105 normal healthy subjects using the Piezoelectric strain gauge technique. The dominant frequency content of a signal was determined using the peak counting method. Values recorded ranged from 70 to 103 Hz, the mean frequency being 83.68 Hz (S.D. +/- 5.78 Hz).

Image-guided surgery: applications to the cervical and thoracic spine and a review of the first 120 procedures.

OBJECT: The authors undertook a study to demonstrate that frameless stereotaxy can be applied safely to the cervical and thoracic spine to minimize complications and associated morbidity. METHODS: A retrospective review of cases was conducted involving the use of an image-guidance system for the accurate placement of surgical implants or for resection of lesions within the cervical and thoracic spine. The outcome measures considered were neural injury, vascular injury, wound infection, surgical revision, and death. CONCLUSIONS: Image-guidance systems are useful intraoperative tools that can be applied accurately to spinal surgery. In addition, such systems can be of great use in the preoperative planning of complex spinal surgery.

Effect of hematoporphyrin derivative photoradiation therapy on survival in the rat 9L gliosarcoma brain-tumor model.

Intracerebral tumors were produced in 99 rats by stereotaxic implantation of 9L gliosarcoma brain-tumor cells. Hematoporphyrin derivative (HPD), 10 or 20 mg/kg, was administered as an intravenous bolus 24 or 48 hours before irradiation of the tumor region with light from an argon pumped-dye laser (632 nm). Laser light, at a dose of 30, 60, or 200 joules/sq cm, was delivered through a craniectomy 10 or 13 days after tumor implantation. Survival times were significantly prolonged in rats exposed to laser light at a dose of 200 joules/sq cm 24 hours after administration of HPD, 20 mg/kg.

Spinal cord pathways mediating somatosensory evoked potentials.

Using a CO2 laser, discrete thoracic spinal cord lesions were made in cats anesthetized with ketamine and xylazine (Rompun). Differences in cortical somatosensory evoked potentials (SEP's) produced with high-intensity stimulation (20 times the motor threshold) of each posterior tibial nerve determined for nine different combinations of unilateral spinal cord lesions. The results of these studies show that nerve fibers in the ipsilateral dorsal column, the ipsilateral dorsal spinocerebellar tract, and the contralateral ventrolateral tracts with respect to the side of leg stimulation, contribute to cortical SEP's. A lesion of the dorsal spinocerebellar tract affected only the early waves (less than 30 msec) of the SEP from leg stimulation ipsilateral to the side of the lesion, whereas a solitary lesion of the ventrolateral tract caused changes primarily in the amplitude of later waves (greater than 30 msec) of the SEP produced by contralateral leg stimulation. Lesions involving one-half of the dorsal column caused changes in the amplitude of both the early and late waves produced by stimulation ipsilateral to the side of the lesion. The effects of various combinations of lesions on the cortical SEP's were not additive, which indicates significant interaction between afferent pathways. These findings suggest that high-intensity peripheral nerve stimulation, which activates both C and A fibers, could be used intraoperatively to assess spinal cord function with more accuracy than the current practice of using a stimulus strength of twice the motor threshold. The importance of using anesthetic agents that do not depress cortical activity (which may affect the later components of the SEP) is also emphasized.

Sources of variance in ocular microtremor.

This study presents a preliminary investigation of the sources of variance in the measurement of ocular microtremor frequency in a normal population. When the results from both experienced and relatively inexperienced operators are pooled, factors that contribute significantly to the total variance include the measurement procedure (p < 0.001), day-to-day variations within subjects (p < 0.001), and inter-subject differences (p < 0.01). Operator experience plays a role in determining the measurement precision: the intra-subject coefficient of variation is about 5% for a very experienced operator, and about 14% for a relatively inexperienced operator.

Ocular microtremor measurement system: design and performance.

The frequency of ocular microtremor (OMT) is related to the functional status of the brain stem, and thus OMT may be useful in the diagnosis and management of brain stem disorders. The paper discusses the design of an OMT measurement system and reports quantitative specifications for three portable systems. All systems use a piezo-electric element as the transducer, which measures the displacement of the sclera during eye rotations. The systems differ in the manner in which the signal is recorded. All systems can detect eye movements corresponding to displacements of the sclera ranging from 12 to over 3000 nm. The frequency responses of all systems are flat (< 2 dB deviation from peak response) between 20 and 150 Hz. The phase response shows deviations (< pi) at the extremes of this range, but qualitative comparison of input and measured signals demonstrates that phase distortion is not excessive. Thus all systems are acceptable for clinical studies involving OMT.

Design of an occipito-cervical fixation device.

Metal plates may be used to stabilize the cervical spine. The plates are attached to the posterior of the vertebra by placing screws into the lateral masses. The plating may be extended, in the form of rod or plate, to connect with and support the occiput. Several problems, such as screw loosening and the plate obscuring the surgeon's view as a screw is being inserted, have been identified with present plate systems. This paper describes the initial design for a cervical fixation device to overcome these problems, and the design and development that was undertaken to enable a prototype device to be manufactured.

Frameless stereotaxy and anterior cervical surgery.

OBJECTIVE: The role of a frameless image guidance system for anterior cervical surgery was evaluated in 40 patients with cervical spondylosis. An assessment was made of the challenges posed in achieving accurate three-dimensional image registration in the absence of multiple fixed anatomical landmarks, and a solution to this problem is outlined using a novel registration tracking device. MATERIALS AND METHODS: Patients underwent preoperative CT scanning of the surgical field of interest, and the image data was reconstructed on a StealthStation (Sofamor Danek, Memphis, Tennessee, USA). An image guidance tracking device was attached to a modified Caspar retractor. Point matching and surface mapping were used for registration. RESULTS: It was not possible to achieve accurate registration in the first 7 patients. In the next 5 patients, the time taken to achieve registration was prolonged. For 28 patients, registration was achieved in an acceptable time with an accuracy of 0.74 +/- 0.4 mm. Anatomical resection margins were accurately identified and 36 anterior cervical screws were precisely placed. CONCLUSIONS: Frameless stereotaxy can now be applied to procedures involving the anterior cervical spine. Potential benefits include accurate definition of the anatomy, demonstration of resection margins, and intraoperative guidance. The technique may prove particularly useful in cases of complex or disrupted anatomy.