Eduardo Alho

Bilateral subthalamic nucleus stimulation for generalized dystonia after bilateral pallidotomy

Thalamotomies and pallidotomies were commonly performed before the deep brain stimulation (DBS) era. Although ablative procedures can lead to significant dystonia improvement, longer periods of analysis reveal disease progression and functional deterioration. Today, the same patients seek additional treatment possibilities.

Surgical Treatment of Myelomeningocele Carried Out at ‘Time Zero’ Immediately after Birth

Background/Aims: To present a protocol of immediate surgical repair of myelomeningocele (MMC) after birth (‘time zero’) and compare this surgical outcome with the surgery performed after the newborn’s admission to the nursery before the operation. Methods: Data from the medical files of 31 patients with MMC that underwent surgery after birth and after admission at the nursery (group I) were compared with a group of 23 patients with MMC admitted and prospectively followed, who underwent surgery immediately after birth – ‘at time zero’ (group II). Results: The preoperative rupture of the MMC occurred more frequently in group I (67 vs. 39%, p < 0.05). The need for ventriculoperitoneal shunt was 84% in group I and 65% in group II and 4 of them were performed during the same anesthetic time as the immediate MMC repair, with no statistically significant difference. Group I had a higher incidence of small dehiscences when compared to group II (29 vs. 13%, p < 0.05); however, there was no statistically significant difference regarding infections. After 1 year of follow-up, 61% of group I showed neurodevelopmental delay, whereas only 35% of group II showed it. Conclusions: The surgical intervention carried out immediately after the birth showed benefits regarding a lower incidence of preoperative rupture of the MMC, postoperative dehiscences and lower incidence of neurodevelopmental delay 1 year after birth.

Deep brain stimulation of the dentate nucleus improves cerebellar ataxia after cerebellar stroke

The cerebrocerebellum receives input from the cerebral cortex and projects to the motor and premotor cortices and the ventrolateral nucleus of the thalamus via the dentate nucleus (DN). Dentothalamocortical projections modulate the activity of the contralateral primary motor (M1) cortex and are involved in movement planning. Acute ischemic injury of the cerebellar nuclei leads to ataxia and a loss of physiologic excitatory inputs from the DN to the contralateral M1 cortex.1 However, chronic cerebellar ischemic lesions have been associated with a reemerging decrease in intracortical inhibition (ICI) in the contralesional M1, leading to marked interhemispheric asymmetry in cortical excitability, which could account for the functional impairment observed after strokes.2

Brain atrophy in primary progressive aphasia involves the cholinergic basal forebrain and Ayala's nucleus

Primary progressive aphasia (PPA) is characterized by left hemispheric frontotemporal cortical atrophy. Evidence from anatomical studies suggests that the nucleus subputaminalis (NSP), a subnucleus of the cholinergic basal forebrain, may be involved in the pathological process of PPA. Therefore, we studied the pattern of cortical and basal forebrain atrophy in 10 patients with a clinical diagnosis of PPA and 18 healthy age-matched controls using high-resolution magnetic resonance imaging (MRI). We determined the cholinergic basal forebrain nuclei according to Mesulams nomenclature and the NSP in MRI reference space based on histological sections and the MRI scan of a post-mortem brain in cranio. Using voxel-based analysis, we found left hemispheric cortical atrophy in PPA patients compared with controls, including prefrontal, lateral temporal and medial temporal lobe areas. We detected cholinergic basal forebrain atrophy in left predominant localizations of Ch4p, Ch4am, Ch4al, Ch3 and NSP. For the first time, we have described the pattern of basal forebrain atrophy in PPA and confirmed the involvement of NSP that had been predicted based on theoretical considerations. Our findings may enhance understanding of the role of cholinergic degeneration for the regional specificity of the cortical destruction leading to the syndrome of PPA.

Novel Treatment Immediately after Myelomeningocele Repair Applying Low-Level Laser Therapy in Newborns: A Pilot Study

Background/Aims: The use of low-level laser therapy (LLLT) in neurosurgery is still hardly disseminated and there are situations in which the effects of this therapeutic tool would be extremely relevant in this medical field. The aim of the present study is to analyze the effect of LLLT on tissue repair after the corrective surgical incision in neonates with myelomeningocele, in an attempt to diminish the incidence of postoperative dehiscences following surgical repair performed immediately after birth. Materials and Methods: Prospective pilot study with 13 patients submitted to surgery at birth who received adjuvant treatment with LLLT (group A). A diode laser CW, λ = 685 nm, p = 21 mW, was applied punctually along the surgical incision, with 0.19 J delivered per point, accounting for a total of 4–10 J delivered energy per patient, according to the surgical wound area and then compared with the results obtained in 23 patients who underwent surgery without laser therapy (group B). Results: This pilot study disclosed a significant decline in dehiscences of the surgical wounds in neonates who were submitted to LLLT (7.69 vs. 17.39%). Conclusion: This new adjuvant therapeutic modality with LLLT aided the healing of surgical wounds, preventing morbidities, as well as shortening the period of hospital stay, which implies a reduction of costs for patients and for the institution.

Subthalamic Nucleus Deep Brain Stimulation: Basic Concepts and Novel Perspectives

Abstract Over the last decades, extensive basic and clinical knowledge has been acquired on the use of subthalamic nucleus (STN) deep brain stimulation (DBS) for Parkinson’s disease (PD). It is now clear that mechanisms involved in the effects of this therapy are far more complex than previously anticipated. At frequencies commonly used in clinical practice, neural elements may be excited or inhibited and novel dynamic states of equilibrium are reached. Electrode contacts used for chronic DBS in PD are placed near the dorsal border of the nucleus, a highly cellular region. DBS may thus exert its effects by modulating these cells, hyperdirect projections from motor cortical areas, afferent and efferent fibers to the motor STN. Advancements in neuroimaging techniques may allow us to identify these structures optimizing surgical targeting. In this review, we provide an update on mechanisms and the neural elements modulated by STN DBS.

Intraoperative dopamine release during globus pallidus internus stimulation in Parkinson's disease

It is still unclear whether dopamine (DA) levels correlate with Parkinsons disease (PD) severity or play a role in the mechanisms of high‐frequency stimulation (HFS).

Endoscopic-guided percutaneous radiofrequency cordotomy

The authors present the first clinical implementation of an endoscopic-assisted percutaneous anterolateral radiofrequency cordotomy. The aim of this article is to demonstrate the intradural endoscopic visualization of the cervical spinal cord via a percutaneous approach to refine the spinal target for anterolateral cordotomy, avoiding undesired trauma to the spinal tissue or injury to blood vessels. Initially, a lateral puncture of the spinal canal in the C1-2 interspace is performed, guided by fluoroscopy. As soon as CSF is reached by the guide cannula (17-gauge needle), the endoscope can be inserted for visualization of the spinal cord and its surrounding structures. The endoscopic visualization provided clear identification of the pial surface of the spinal cord, arachnoid membrane, dentate ligament, dorsal and ventral root entry zone, and blood vessels. The target for electrode insertion into the spinal cord was determined to be the midpoint from the dentate ligament and the ventral root entry zone. The endoscopic guidance shortened the fluoroscopy usage time and no intrathecal contrast administration was needed. Cordotomy was performed by a standard radiofrequency method after refining of the neurophysiological target. Satisfactory analgesia was provided by the procedure with no additional complications or CSF leak. The initial use of this technique suggests that a percutaneous endoscopic procedure may be useful for particular manipulation of the spinal cord, possibly adding a degree of safety to the procedure and improving its effectiveness.

Neuronavigation-guided transcranial magnetic stimulation of the dentate nucleus improves cerebellar ataxia: A sham-controlled, double-blind n = 1 study

Lesions of the cerebellum can lead to hypotonia, ataxia, intention tremor, and dystonia [1], which can be disabling and resistant to conventional treatments. The cerebrocerebellum receives input exclusively from the cerebral cortex (via pontine nuclei) and projects to the motor, premotor, and prefrontal cortices and to the ventrolateral nucleus of the thalamus via the dentate nucleus. It is involved in motor planning, motor learning, and fine-tuning of the motor activity, mainly by evaluating disparities between intention and action during the execution of movement. Cerebellar projectionsmodulate activity in the contralateral primarymotor cortex (M1) through dentothalamocortical projections. Acute ischemic damage to the deep cerebellar nuclei is known to result in ataxia and loss of excitatory input to the contralateral M1 cortex [1]. However, chronic cerebellar ischemic lesions have recently been associated with reemerging increase in intracortical inhibition in the contralesional M1, leading to marked inter-hemispheric asymmetry in cortical excitability, which could account for part of the functional impairment seen after stroke [2]. We report a case of post-surgical unilateral cerebellar infarction leading to dystonia, intention tremor, and ataxia treated by inhibitory low-frequency neuronavigated repetitive transcranial magnetic stimulation (rTMS) to the healthy cerebellar hemisphere. The aim was to decrease the functional cortical asymmetry related to chronic cerebellar infarction [2]. We hypothesized that this treatment would balance the functional asymmetry seen between both M1 after chronic cerebellar and attenuate clinical symptoms. A 50-year-old female underwent a resection of a right acoustic neuroma in 2006, which was complicated by ischemia of the right cerebellar hemisphere (Fig. 1A). She developed severe axial and appendicular ataxia, mostly on the right, with significant impairment in functioning. A few months later, she developed bilateral involuntary hand and cervical dystonia (documented by electroneuromyographic study), which was refractory to medical treatment. Several treatments were attempted for the cerebellar tremor, including: physical therapy, benzodiazepines, biperidene, beta-adrenergic blocking agents, and primidone, without satisfactory symptomatic improvement. The patient declined deep brain stimulation for symptomatic tremor control. Because of the refractory nature of the symptoms, the subject consented to neuronavigated low-frequency TMS to the healthy dentate nucleus. A double-blind sham-controlled trial of 1 Hz neuronavigated rTMSwas performed on the left dentate nucleus with a refrigerated double-cone rTMS coil (cooled DB-80, Magventure TonikaElektronik, Denmark), which allows for the stimulation of deep structures up to 4e5 cm from the coil center. The dentate nucleus lay 50 mm deep from the skull surface, a distance similar to that of the skull vertex to the leg area at M1 (48 mm) (Fig. 1B). We detected the “hot spot” for M1 distal leg representation (peroneus longus muscle), and then its rest motor threshold was measured. The left dentate nucleus was then targeted by neuronavigation and a 1500-pulse session of either active or sham stimulation was performed at 90% of the rest motor threshold of the leg M1 area. Two (active or sham) stimulation sessions were randomly performed four weeks apart. Clinical assessment and video recording were performed using validated tools before stimulation and one week after by movement disorder specialist blinded to the study. After the active session, there was improvement in tremor (Fahn, Tolosa, Marin Tremor Rating Scale before 1⁄4 38/144; after 1⁄4 24/ 144 37% reduction) and in cerebellar ataxia (scale for the assessment and rating of ataxia [SARA] before 1⁄4 25.5/40, after 1⁄4 17/40) (see video). The Patient Global Impression of Change (measured on a seven-point Leikert scale ranging from 1 to 7) was 6 after the active session (i.e. moderately improved) and 3 after the sham procedure (i.e. no change). There was no change in her dystonia after active treatment (Unified Dystonia Rating Scale 1⁄4 9/112 before, and 9/112 after active stimulation). There was no clinical improvement after sham stimulations using the same rating scales Table 1. Supplementary data related to this article can be found online at http://dx.doi.org/10.1016/j.parkreldis.2015.05.010.

Multimodal Whole Brain Registration: MRI and High Resolution Histology

Three-dimensional brain imaging through cutting-edge MRI technology allows assessment of physical and chemical tissue properties at sub-millimeter resolution. In order to improve brain understanding as part of diagnostic tasks using MRI images, other imaging modalities to obtain deep cerebral structures and cytoarchitectural boundaries have been investigated. Under availability of postmortem samples, the fusion of MRI to brain histology supports more accurate description of neuroanatomical structures since it preserves microscopic entities and reveal fine anatomical details, unavailable otherwise. Nonetheless, histological processing causes severe tissue deformation and loss of the brain original 3D conformation, preventing direct comparisons between MRI and histology. This paper proposes an interactive computational pipeline designed to register multimodal brain data and enable direct histology-MRI correlation. Our main contribution is to develop schemes for brain data fusion, distortion corrections, using appropriate diffeomorphic mappings to align the 3D histological and MRI volumes. We describe our pipeline and preliminary developments of scalable processing schemes for highresolution images. Tests consider a postmortem human brain, and include qualitatively and quantitatively results, such as 3D visualizations and the Dice coefficient (DC) between brain structures. Preliminary results show promising DC values when comparing our scheme results to manually labeled neuroanatomical regions defined by a neurosurgeon on MRI and histology data sets. DC was computed for the left caudade gyrus (LC), right hippocampus (RH) and lateral ventricles (LV).