Imaging and Surgical Findings in Patients with Hemi-Laryngopharyngeal Spasm and the Potential Role of MRI in the Diagnostic Work-Up.

BACKGROUND AND PURPOSE: Hemi-laryngopharyngeal spasm is a recently discovered condition characterized by episodic coughing and unilateral throat contractions that may lead to severe stridor. These symptoms are caused by a vascular compression of the ipsilateral vagus nerve, typically the PICA. Microvascular decompression of the vagus nerve has been demonstrated to be a potential cure for this neurovascular compression syndrome. The main aim of this study was to clarify the role of MR imaging in the diagnostic work-up of this rare condition. MATERIALS AND METHODS: We describe the imaging and surgical findings of 3 patients from our prospective case series of patients with hemi-laryngopharyngeal spasm from 2015 to 2017. Second, the imaging data of 100 patients (control cohort) with symptoms unrelated to hemi-laryngopharyngeal spasm were reviewed to investigate the rate and degree of neurovascular conflict of the vagus nerve. RESULTS: All patients with hemi-laryngopharyngeal spasm reported to date have had vascular compression of the vagus nerve due to the PICA. In the control cohort, there was a good interrater agreement in scoring the "contact" and "compression" of the vagus nerve (κ = 0.73. P = < .001). The frequency of contact or compression of the vagus nerve was approximately 50%. The PICA was the most frequent vessel involved in 74%. CONCLUSIONS: The presence of unilateral neurovascular contact or compression of the vagus nerve does not confirm the diagnosis of hemi-laryngopharyngeal spasm. The MR imaging finding of ipsilateral vascular compression of the vagus nerve is a necessary but not sufficient finding for the diagnosis of hemi-laryngopharyngeal spasm.

Electrophysiologic Validation of Diffusion Tensor Imaging Tractography during Deep Brain Stimulation Surgery.

BACKGROUND AND PURPOSE: Diffusion tensor imaging fiber tractography-assisted planning of deep brain stimulation is an emerging technology. We investigated its accuracy by using electrophysiology under clinical conditions. We hypothesized that a level of concordance between electrophysiology and DTI fiber tractography can be reached, comparable with published modeling approaches for deep brain stimulation surgery. MATERIALS AND METHODS: Eleven patients underwent subthalamic nucleus deep brain stimulation. DTI scans and high-resolution T1- and T2-weighted MR imaging was performed at 3T. Corticospinal tracts were traced. We studied electrode positions and current amplitudes that elicited corticospinal tract effects during the operation to determine relative corticospinal tract distance. Postoperatively, 3D deep brain stimulation electrode contact locations and stimulation patterns were applied for the same corticospinal tract distance estimation. RESULTS: Intraoperative electrophysiologic (n = 40) clinical effects in 11 patients were detected. The mean intraoperative electrophysiologic corticospinal tract distance was 3.0 ± 0.6 mm; the mean image-derived corticospinal tract distance (DTI fiber tractography) was 3.0 ± 1.3 mm. The 95% limits of agreement were ±2.4 mm. Postoperative electrophysiology (n = 44) corticospinal tract activation effects were encountered in 9 patients; 39 were further evaluated. Mean electrophysiologic corticospinal tract distance was 3.7 ± 0.7 mm; for DTI fiber tractography, it was 3.2 ± 1.9 mm. The 95% limits of agreement were ±2.5 mm. CONCLUSIONS: DTI fiber tractography depicted the medial corticospinal tract border with proved concordance. Although the overall range of measurements was relatively small and variance was high, we believe that further use of DTI fiber tractography to assist deep brain stimulation procedures is advisable if inherent limitations are respected. These results confirm our previously published electric field simulation studies.

Evidence of ancillary trigeminal innervation of levator palpebrae in the general population.

The cranial synkineses are a group of disorders encompassing a variety of involuntary co-contractions of the facial, masticatory, or extraocular muscles that occur during a particular volitional movement. The neuroanatomical pathways for synkineses largely remain undefined. Our studies explored a normal synkinesis long observed in the general population - that of jaw opening during efforts to open the eyelids widely. To document this phenomenon, we observed 186 consecutive participants inserting or removing contact lenses to identify jaw opening. Seeking electrophysiological evidence, in a second study we enrolled individuals undergoing vascular decompression for trigeminal neuralgia or hemifacial spasm, without a history of jaw-winking, ptosis, or strabismus, to record any motor responses in levator palpebrae superioris (LPS) upon stimulation of the trigeminal motor root. Stimulus was applied to the trigeminal motor root while an electrode in levator recorded the response. We found that 37 participants (20%) opened their mouth partially or fully during contact lens manipulation. In the second study, contraction of LPS with trigeminal motor stimulation was documented in two of six patients, both undergoing surgery for trigeminal neuralgia. We speculate these results might provide evidence of an endogenous synkinesis, indicating that trigeminal-derived innervation of levator could exist in a significant minority of the general population. Our observations demonstrate plasticity in the human cranial nerve innervation pattern and may have implications for treating Marcus Gunn jaw-winking.

Minimizing brain shift during functional neurosurgical procedures - a simple burr hole technique that can decrease CSF loss and intracranial air.

BACKGROUND: Exact stereotactic placement of deep brain stimulation electrodes during functional stereotactic neurosurgical procedures can be impeded by intraoperative brain shift. Brain shift has been shown to correlate with the amount of intracranial (subdural) air detected on early postoperative imaging studies. We report a simple burr hole technique that reduces the loss of cerebrospinal fluid (CSF) and has the potential to significantly reduce the amount of postoperative intracranial air. MATERIAL AND METHODS: A total of 16 patients were studied with half (group 2) receiving the burr hole technique designed to seal the CSF space and thereby reducing CSF loss. The other 8 patients (group 1) received the standard burr hole technique. The 2 groups were of similar age, gender, diagnosis (Parkinson's disease, n=14; cervical dystonia n=2), and surgical targets. All patients received bilateral electrodes either in the subthalamic nucleus (STN, n=14) or in the globus pallidum internus (GPi, n=2) avoiding transventricular trajectories. Early postoperative 3-dimensional computed tomography (3D CT) was used to check for possible bleeding, DBS lead location, and the amount of intracranial air. Intracranial air was assessed manually in a volumetric slice-by-slice approach in the individual postoperative CT and the groups compared by t-test. RESULTS: Group 2 showed significantly lower postoperative intracranial air volumes (4.86 ± 4.35cc) as compared to group 1 (27.59 ± 17.80 cc, p=0.0083*). The duration of surgery, however, was significantly longer for group 1 (435 ± 56.05 min) as compared to group 2 (316 ± 34.79 min,p=0.00015*).The time span between the conclusion of the operation and postoperative 3DCT was similar for both groups. CONCLUSION: This new and simple burr hole technique was associated with a significant reduction in postoperative intracranial air. Reduction of intracranial air will ultimately reduce brain shift. That total operation time does not influence intracranial air is discussed as well as the limitations of this pilot series. In the authors' opinion, this straightforward and cost-effective technique has the potential to reduce brain shift and to increase DBS placement accuracy during functional stereotactic neurosurgical procedures performed in the seated or half-sitting position. A larger more standardized patient series is necessary to substantiate the findings.

Localization of the subthalamic nucleus: optimization with susceptibility-weighted phase MR imaging.

BACKGROUND AND PURPOSE: On clinical MR images, the subthalamic nuclei (STN) are poorly delineated from adjacent structures, impeding safe direct targeting for placement of electrodes in the treatment of Parkinson disease. Susceptibility-weighted MR phase imaging offers improved contrast and spatial resolution at reduced imaging times relative to clinically used T2-weighted spin-echo imaging for STN visualization. Our purpose was to assess STN visibility by using phase imaging, comparing phase and magnitude images obtained concurrently by using susceptibility-weighted imaging (SWI). The goal was to identify an efficient scanning protocol for high-quality phase images of STN. MATERIALS AND METHODS: Seventy-eight SWI scans were acquired at 3T by using different TEs and acceleration factors. STN visibility and delimitation from adjacent structures were scored from 0 (not interpretable) to 5 (excellent). Regression analyses assessed the relationship of STN visibility to scanning parameters RESULTS: STN were identified at all studied TEs on phase images. Visibility and delimitation of STN were consistently superior on phase images compared with magnitude images. Good visualization (score of >or=4) of STN on phase imaging occurred at a mean TE of 20.0 ms and a sensitivity encoding (SENSE) of 1.40. Scores of STN visualization on phase images were dependent on SENSE (P < .002) and TE (P < .031). Good delimitation of the STN on phase imaging occurred at a mean TE of 21.6 ms and a SENSE of 1.36. CONCLUSIONS: Visualization and delimitation of STN was superior on phase images and was achieved at 3T in <2.5 minutes. A TE of 20 ms and an acceleration factor of

Fiber tracking with distinct software tools results in a clear diversity in anatomical fiber tract portrayal.

BACKGROUND: Fiber tract portrayal, based on diffusion tensor imaging (DTI), is becoming more and more important in functional neuronavigation. No standard exists to guarantee anatomically correct fiber tract depiction for neurosurgical purposes. Therefore, showing the anatomically correct extension of fiber tracts beyond the pure connection of functional areas remains an area of important research and investigation. Standards for fiber tracking software applications are elusive. The purpose of this study was to compare the performance of different fiber tracking software tools (FT-tools). We tested the software performance, comparability and anatomical accuracy of the tracking results of several programs. MATERIAL AND METHODS: A single DTI dataset of a healthy control subject was submitted to four different fiber tracking software applications (two commercial, two freeware), three of them based on Fiber Assignment by Continuous Tracking, one based on the Tensorline Propagation Algorithm. The corticospinal tract (CST) was investigated. The tracking procedure was controlled by the following input variables: single regions of interest (ROIs): brain stem, or internal capsule, or subcortical white matter of the precentral gyrus; background threshold, fractional anisotropy (FA) threshold, maximum fiber angulation and fiber length. Tracking results were compared for 2-D correlated triplanar images (axial, coronal, sagittal) and in 3-D. For all FT-tools, the time used to generate the CST was measured. The inter-rater variability for tracking time and for the tracked CST volumes was recorded for two of the four FT-tools. RESULTS AND CONCLUSIONS: Distinct FT-tools performed very differently with respect to the time required to achieve CST portrayal (track generation time varied between 16 and 50 min). None of the software applications was able to display the CST in its full anatomical extent. Especially the lateral precentral areas were not pictured. Surprisingly, the application of the four distinct FT-tools did not lead to comparable tracking results. As very similar or identical tracking algorithms were used, this difference cannot be easily explained. Clearly, neurosurgeons have to be cautious about applying fiber tracking results intraoperatively, especially when dealing with an abnormal or distorted fiber tract anatomy. The authors recommend the use of adjunct strategies such as intraoperative electrophysiology to enhance patient safety and improve anatomical accuracy when using tracking results for surgical procedures.

Noradrenergic modulation of subthalamic nucleus activity in human: metoprolol reduces spiking activity in microelectrode recordings during deep brain stimulation surgery for Parkinson's disease.

BACKGROUND: Reversible changes in subthalamic nucleus (STN) activity, detected by microelectrode recording (MER), are reported in three patients who received an intravenous betablocker, metoprolol, during deep brain stimulation (DBS) for Parkinson's disease (PD). METHODS: Metoprolol (MP) was given intravenously to reduce blood pressure during surgery. Systolic blood pressure dropped by 4, 11 and 17%, indicating a systemic beta - adrenoceptor blocking effect. FINDINGS: In all patients, the bursting spiking activity of the STN was temporarily suppressed, after the application of MP. Unexpectedly, a transient reduction in Parkinson symptoms (rigidity) was recorded during suppression of STN spiking activity in patient 2. CONCLUSION: The reversible suppression of STN activity and Parkinson symptoms with the beta1-selective adrenoceptor antagonist MP has not been reported. It supports the theory, that--as recently reported in the rat--the human STN is influenced by adrenergic inputs. This report supports the possible application of adrenergic antagonist drugs for the use in Parkinson's disease and advocates additional neurophysiological and pharmacological research in this field.

Recurrent trigeminal neuralgia secondary to Teflon felt.

The authors present a case of a 45-year-old man with recurrent trigeminal neuralgia twelve years after microvascular decompression. The patient underwent surgical reexploration of the trigeminal nerve. A piece of hardened Teflon felt was found piercing a hole through the trigeminal nerve. No other compression of the nerve was found. Removal of the Teflon felt resolved the neuralgia. To the authors knowledge this is the first report of recurrent trigeminal neuralgia due to such a mechanism. This case emphasises the need for further improvement of the surgical technique for microvascular decompression of the trigeminal neuralgia.

Hypomania as an adverse effect of subthalamic nucleus stimulation: report of two cases.

Mania following subthalamic nucleus (STN) deep brain stimulation (DBS) is well described and obvious to both the patient and their physician. The authors describe two patients who developed hypomania following STN-DBS but were unaware of their mood disturbance. Two Parkinson's patients with no previous mood disorders received bilateral STN electrodes. Both experienced dramatic improvement in their motor function and neither complained of any side effects. Their families reported detrimental hypomanic behaviour. Readjusting the stimulation parameters resolved the hypomania with continued motor benefits. The authors draw attention to potential adverse effects of STN-DBS that might be neglected by patients.

Artistic assault: an unusual penetrating head injury reported as a trivial facial trauma.

The authors report a case of penetrating head injury that presented with a deceptively mild complaint. To our knowledge, it is the first report of a paint brush penetrating the brain. The patient reported being punched in the left eye and presented with a minor headache, swelling around the left orbit, a small cut on the cheek and slightly reduced left eye abduction. After radiological evaluation, a penetrating head injury was diagnosed. Under general anesthesia, through a lateral eyelid incision a 10.5 cm long paint brush, which had penetrated from the left orbit to the right thalamus, was removed. No post-operative infection was seen at six months follow-up. This brief report serves to highlight that penetrating brain injury can occur without neurological deficit and that a minimally invasive surgical approach was successful in avoiding any complications.

PET imaging of implanted human retinal pigment epithelial cells in the MPTP-induced primate model of Parkinson's disease.

Human retinal pigment epithelial (hRPE) cells produce L-dopa, are easily harvested and expanded in culture, and, attached to microcarriers, can survive in the brain without immunosuppression. Studies in rats, primates, and parkinsonian patients have demonstrated that striatally implanted hRPE cells attached to gelatin microcarriers (RPE-GM) are able to improve parkinsonian symptoms and are well tolerated for extended periods. In moderately to severely impaired monkeys with bilateral 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP)-induced parkinsonism receiving a unilateral RPE-GM implant in the putamen, there was a 39% improvement in clinical scores over the first 2 months post-implant. Positron emission tomography (PET) with [18F]fluoro-L-dopa (FDOPA) showed increased accumulation in the implanted putamen and a concomitant decrease in [11C]raclopride binding in the same area, suggesting increased dopamine release compared to the contralateral putamen. We report the first in vivo visualization of hRPE cells and their effects, implicating a dopaminergic mechanism of action.

Stereotaxic intrastriatal implantation of human retinal pigment epithelial (hRPE) cells attached to gelatin microcarriers: a potential new cell therapy for Parkinson's disease.

Human retinal pigment epithelial (hRPE) cells are dopaminergic support cells in the neural retina. Stereotaxic intrastriatal implantation of hRPE cells attached to gelatin microcarriers (Spheramine) in rodent and non-human primate models of Parkinson's disease (PD) produces long term amelioration of motor and behavioral deficits, with histological and PET evidence of cell survival without immunosuppression. Long-term safety in cynomologous monkeys has also been demonstrated. Six H&Y stage III/IV PD patients were enrolled in a one-year, open-label, single center study to evaluate the safety and efficacy of Spheramine (approximately 325,000 cells) implanted in the most affected post-commissural putamen. All patients tolerated the implantation of Spheramine well and demonstrated improvement. At 6, 9, and 12 months post-operatively, the mean UPDRS-Motor score "off", the primary outcome measure, improved 33%, (n = 6), 42% (n = 6), and 48% (n = 3), respectively. No "off-state" dyskinesias have been observed. Based on these preliminary results, Spheramine appears to show promise in treating late stage PD patients.

The antioxidant enzyme quinone reductase is up-regulated in vivo following cerebral ischemia.

An astrocyte antioxidant enzyme, quinone reductase (QR), was studied in vivo to assess whether its activity was up-regulated following cerebral ischemia. Rats were given a unilateral focal cerebral infarct and regions of interest within the ischemic penumbra compared to the non-ischemic side for QR activity. At 7 days post-ischemia, QR activity was significantly up-regulated within cells of astrocyte morphology in the cortex (p = 0.007) and subcortical (p = 0.005) areas adjacent to the infarct. This enzyme activity peaked at 7 days but was still significantly up-regulated at 14 days. Up-regulation of QR activity occurs within the ischemic penumbra of a stroke in this animal model and may contribute to factors that limit ischemic damage to neurons in this area.

Preferential expression of antioxidant response element mediated gene expression in astrocytes.

Transcriptional control of target genes by antioxidant/electrophile response elements has been well described in peripheral tissues. Genes that are regulated by this mechanism include the antioxidant enzymes NAD(P)H:quinone oxidoreductase, gamma-glutamyl cystine synthetase and glutathione-S-transferase. Antioxidant/electrophile response elements within a gene's promoter confer induction by low-molecular-weight electrophilic compounds such as tert-butylhydroquinone and dimethyl fumarate. We have now examined the ability of antioxidant/electrophile response elements to elicit gene expression in neurons and astrocytes in both brain slices and primary cultures using transient transfection of promoter reporter constructs. Our results using a heat-stable human placental alkaline phosphatase reporter indicate that antioxidant/electrophile response element mediated gene expression is largely restricted to astrocyte cell populations. Placental alkaline phosphatase expression was significantly elevated in astrocytes treated with the antioxidant/electrophile response element inducer dimethyl fumarate. Mutant constructs lacking a functional antioxidant/electrophile response element abolished all placental alkaline phosphatase expression in astrocytes. We suggest that astrocytic metabolic processes that normally aid and/or protect neurons may be controlled via this inducible system.

Microelectrode recording for pallidotomy: mandatory, beneficial or dangerous?

There is an active debate regarding whether pallidotomy should be performed with microelectrode recording or macroelectrode stimulation. A meta-analysis was performed on the published reports (1992-2000) of unilateral pallidotomy for Parkinson's disease to determine if the outcome or complications of this procedure significantly differed between these two techniques. Papers were excluded if they followed a cohort of less than ten patients, had follow-up less than three months, or included previously reported patients. There were no significant differences between the two techniques in improvement of dyskinesia (p = 0.66) or UPDRS motor score (p = 0.62). Microelectrode recording had a significantly higher (p = 0.012) intracerebral hemorrhage rate (1.3 +/- 0.4%) compared to macroelectrode stimulation (0.2 +/- 0.2%).

A prospective randomized comparison of CT and MRI pre-operative localization for pallidotomy.

OBJECTIVE: During the pallidotomy procedure, is pre-operative localization with MRI more accurate than CT and does it result in a significant difference in surgical outcome? METHODS: Twenty-four Parkinson's Disease patients received a unilateral pallidotomy for their motor symptoms. Dyskinesia was scored pre- and six weeks postoperatively. All patients had a pre-operative CT scan and MRI to calculate the target co-ordinates. Patients were then randomly selected to proceed with either the CT or MRI coordinates. The final position for the lesion was determined with intraoperative macrostimulation and impedance measurements. The percentage improvement of dyskinesia was noted for each patient and the two groups compared by the Mann-Whitney test. The distance from the final target to the MRI and CT pre-operative co-ordinates were calculated for each patient. The mean distance for each modality was then compared by Student's t-test. The number of electrode repositionings was also recorded for each patient and the two groups compared by the nonparametric Mann-Whitney test. RESULTS: Although the MRI co-ordinates were significantly (p<0.023) closer to the final target, this did not translate into a significant reduction in electrode repositionings. There was no significant difference in the improvement in dyskinesia between the two groups. CONCLUSIONS: The pre-operative MRI co-ordinates were significantly (p=0.023) closer to the final target than those from the CT. The potential advantages and disadvantages of both imaging modalities are reviewed. There was no significant difference in surgical outcome using either MRI or CT for pre-operative localization in pallidotomy.