An atypical presentation of diffuse midline pontine glioma in a middle age patient: Case report.

INTRODUCTION: Diffuse midline glioma is a newly WHO defined entity (grade IV) (Louis et al., 2016) which includes diffuse intrinsic pontine glioma (DIPG) reported in pediatric population and, occasionally, in young adults. Here, we present a detailed description of an atypical case of diffuse midline glioma in a 53 years old woman. CASE REPORT: A caucasian woman aged 53 from Ukraine, was referred to another neurological department complaining of 3 months history of progressive postural instability and gait impairment with frequent falling. Magnetic resonance demonstrated two brainstem lesions, hyperintense in FLAIR with "patchy" peripheral enhancement, leptomeningeal and cranial nerves enhancement. CSF was normal. Due to positive antinuclear antibodies test (ANA 1:360), intravenous steroid treatment was administered and reported to initially improve the patient condition. However, the following weeks the lady worsened. Imaging features were unchanged. Because quantiferon test resulted positive, MRI-Spectroscopy showed an inflammatory pattern and MRI perfusion study and brain FDG-PET, were normal, tubercolar granulomatous hypothesis was initially favored. Antitubercular therapy with isoniazid, pyrazinamide, ethambutol and rifampicin was started without any clinical improvement. Hence, the biopsy was proposed. The procedure revealed a diffuse midline pontine glioma. Considering the advanced stage of the disease, radiotherapy was not indicated. Patient died after eight months from the onset of neurological disturbances. CONCLUSION: Our case shows that diffuse midline glioma is a CNS tumor not limited to young population but occurring also in middle aged patients with an insidious pattern. We therefore recommend to perform biopsy at very early stages in patients with atypical brainstem lesions.

Autologous transplantation of muscle-derived CD133+ stem cells in Duchenne muscle patients.

Duchenne muscular dystrophy (DMD) is a lethal X-linked recessive muscle disease due to defect on the gene encoding dystrophin. The lack of a functional dystrophin in muscles results in the fragility of the muscle fiber membrane with progressive muscle weakness and premature death. There is no cure for DMD and current treatment options focus primarily on respiratory assistance, comfort care, and delaying the loss of ambulation. Recent works support the idea that stem cells can contribute to muscle repair as well as to replenishment of the satellite cell pool. Here we tested the safety of autologous transplantation of muscle-derived CD133+ cells in eight boys with Duchenne muscular dystrophy in a 7-month, double-blind phase I clinical trial. Stem cell safety was tested by measuring muscle strength and evaluating muscle structures with MRI and histological analysis. Timed cardiac and pulmonary function tests were secondary outcome measures. No local or systemic side effects were observed in all treated DMD patients. Treated patients had an increased ratio of capillary per muscle fibers with a switch from slow to fast myosin-positive myofibers.

Altered subthalamo-pallidal synchronisation in parkinsonian dyskinesias.

The aim of this work was to study the role of subthalamo-pallidal synchronisation in the pathophysiology of dyskinesias. We recorded local field potentials (LFPs) in a patient with Parkinson's disease and left surgery induced dyskinesias with double, bilateral deep brain stimulation electrode implants in the subthalamic nucleus (STN) and the globus pallidus internus (GPi). Synchronisation was studied through coherence analysis. In the nuclei contralateral to the dyskinetic side of the body there was decreased STN-GPi coherence in the high beta range (20-30 Hz) and an enhanced coherence at low frequencies (<10 Hz). Despite the possible limitations arising from single-case observations, our findings suggest that parkinsonian dyskinesias are related to altered synchronisation between different structures of the basal ganglia. Firing abnormalities within individual basal ganglia nuclei are probably not enough to account for the complex balance between hypokinetic and hyperkinetic symptoms in human parkinsonian dyskinesias and altered interactions between nuclei should also be considered.

The subthalamic nucleus in Parkinson's disease: power spectral density analysis of neural intraoperative signals.

To test a new tool for the neurophysiological identification of the human subthalamic nucleus (STN) during stereotactic surgery for the implantation of deep-brain-stimulation (DBS) electrodes, we analysed off-line the intraoperative signals recorded from patients with Parkinson's disease. We estimated the power spectral density (PSD) along each penetration track (8 patients, 13 sides) and determined the spatial correlation of the PSD with the target location estimated from neuroimaging procedures ("anatomical target"), and with the final target location derived from standard intraoperative neurophysiological procedures for STN localization ("clinical target"). At each step we recorded the 'on-line' signal for 120 seconds; because the PSD was estimated by calculating the periodogram for 6-second epochs of neural signal, we had 20 epochs at each step. When the electrode track crossed the STN, the PSD in the 0.25-2.5 kHz band increased, peaking on average <0.5 mm cranial to the clinical target and 1.00+/-1.51 mm caudal to the anatomical target. When the track was outside the nucleus, the PSD remained unchanged. Even on recordings with low signal-to-noise ratio, off-line PSD analysis of neural signals showed a good correspondence with the target indicated by the surgical team. On-line intraoperative estimation of the PSD may be a simple, reliable, rapid and complementary approach to electrophysiological monitoring during STN surgery for Parkinson's disease.

Multiple sequential image-fusion and direct MRI localisation of the subthalamic nucleus for deep brain stimulation.

AIM: Deep brain stimulation (DBS) is the treatment of choice for advanced Parkinson's disease. The target co-ordinates are traditionally calculated in relation to the intercommissural distance. Anterior (AC) and posterior commissures (PC) may be visualised by the means of ventriculography, CT or MRI. METHODS: We have studied the efficacy of direct visualisation of the subthalamic-red nucleus complex on MRI, the advantage of fusion of stereotactic CT and MR images (Multiple Sequences Image Fusion - MuSIF). These methods are combined with double check of indirect calculation of the target co-ordinates based on AC-PC line, as well as the corrispondence to the stereotactic electronic atlas. RESULTS: Subthalamic nucleus (STN) was well recognisable in fused images in all 22 sides. At 3 months from surgery it was possible to reduce 76% of L-dopa equivalent daily dose. Dyskine-sias reduced to 50% and motor fluctuation up to 45%. CONCLUSION: In our experience MuSIF offers very high rate of accuracy in calculation of target co-ordinates. Direct visualisation of STN in MR and MuSIF are reliable and facilitate the accuracy of identification of target co-ordinates. Intraoperative neurophysiological recording increases the accuracy of microelectrode position.

Do intraoperative microrecordings improve subthalamic nucleus targeting in stereotactic neurosurgery for Parkinson's disease?

AIM: The clinical importance of intraoperative microrecordings for subthalamic nucleus (STN) localization in neurosurgical practice remains a matter of debate in the various groups. METHODS: To investigate their usefulness in localizing the STN, we retrospectively evaluated how intraoperative microelectrode recordings changed the targeting of the STN estimated only on intraoperative stimulation and neuroanatomic targeting procedures. For neuroradiologic targeting of the nucleus we used a TC-MRI fusion algorithm and direct visualization of the STN. Besides standard microrecordings we also analyzed the power spectral density (PSD) pattern of physiological signals along the track and its neuroanatomic and clinical correlations. RESULTS: In our series of 12 patients with Parkinson's disease undergoing surgery for implantation of deep-brain stimulation (DBS) electrodes in the STN we found that in 25% (1/4) of patients, microrecordings determined the choice of the optimal track. In all the tracks analyzed the PSD peak coincided with the point selected for the final electrode implantation on the basis of the standard procedure for intraoperative monitoring based on both microstimulation and recordings. CONCLUSION: Intraoperative microrecordings are of determinant importance for accurate STN localization and are essential for optimal results in neurosurgical practice. PSD analysis is a simple and quick quantitative signal descriptor that will probably provide even more precise, simple and rapid tool for intraoperative neurophysiological localization of the STN.

Deep brain stimulation for Parkinson's disease: the experience of the Policlinico-San Paolo Group in Milan.

Thirty patients with idiopathic Parkinson's disease were treated with deep brain stimulation electrode in the subthalamic nucleus. After surgery, the patients' best mean Unified Parkinson's Disease Rating Scale (UPDRS III) scores (medictionOFF-stimulatorON versus preoperative medicationOFF) were 77+/-14% at 3 months ( n=20 patients) and 72+/-14% at 12 months follow-up ( n=16). The mean reduction in therapy (expressed in levodopa dose equivalents in mg) was 68+/-25% at 12 months. Postoperative complications were rare, mostly mild, and reversible. Therapeutic success depends on a multidisciplinary team approach, meticulous patient selection, including patients' cognitive, psychic, and behavioral status, and patient and family lifestyles.

Anatomo-clinical correlation of intraoperative stimulation-induced side-effects during HF-DBS of the subthalamic nucleus.

The efficacy of deep brain stimulation of the subthalamic nucleus (STN) is dependent on the accuracy of targeting. In order to reduce the number of passes and, consequently, the duration of surgery and risk of bleeding, we have set up a new method based on direct magnetic resonance imaging (MRI) localisation of the STN. This procedure allows a short duration of the neurophysiological session (one or two initial tracks). Whenever a supplementary track is needed, the stimulation-induced side effects are analysed to choose from one of the remaining holes in Ben's gun. A good knowledge of anatomical structures surrounding the STN is mandatory to relate side effects to the actual position of the track. In our series of 11 patients (22 sides, 37 tracks), the most common and reproducible side effects were those characterised by motor, sensorial, oculomotor and vegetative signs and symptoms. Moreover, the therapeutic window (distance between the current intensity needed to obtain the best clinical effect and the intensity capable to induce side effects) predicted clinical efficacy in the long-term, and contributed to the choice of which among the examined tracks had to be implanted with the chronic macroelectrode.

Visualisation of the subthalamic nucleus: a multiple sequential image fusion (MuSIF) technique for direct stereotaxic localisation and postoperative control.

A novel multiple, sequential image fusion (MuSIF) procedure merging stereotaxic CT with frameless magnetic resonance imaging (MRI) is used since June 2000 to visualise and directly localise the subthalamic nucleus (STN) on T2 images. In 13 consecutive Parkinson's cases, intraoperative recording and stimulation verified bilateral electrode implantation guided by fused T2 images. In 85% of sides, final implantation opted for visualised target track. Implanted electrode position on postoperative T2 images matched planned target. Clinical follow-up reproduces literature's best results. This MuSIF technique, effective for direct STN targeting, has practical advantages: MRI can be performed regardless of surgery time; regular MR scanning to correct real image distortion is unneeded; and the need for multiple localising tracks is reduced by enabling us to account for each patient's STN anatomy.

Corticospinal potentials after transcranial stimulation in humans.

The descending volley evoked in humans by transcranial electrical stimulation of the scalp was recorded with epidural and spinal electrodes. It consisted of an early wave, which increased in amplitude and decreased in latency when the strength of the stimulus was increased. The mean conduction velocity of the early wave was 66, SD 2.5 m/s. At high stimulus intensity this wave was followed by later and smaller waves, which travel at the same speed as the initial potential. The recovery cycle of the descending volley was studied by delivering paired cortical stimuli at time intervals ranging from 0.5 to 10 ms. The early wave evoked by the test stimulus recovered to about 50% at a 1 ms interval and to 100% at a 3.5 ms interval. The later waves could not be tested at short time intervals but with time intervals longer than 3.5 ms they recovered to 100%. It is suggested that the initial and later waves after scalp stimulation are equivalent to the D and I waves seen in animal experiments.