Gaddum D. Reddy

Three-dimensional random access multiphoton microscopy for functional imaging of neuronal activity

The dynamic ability of neuronal dendrites to shape and integrate synaptic responses is the hallmark of information processing in the brain. Effectively studying this phenomenon requires concurrent measurements at multiple sites on live neurons. Substantial progress has been made by optical imaging systems that combine confocal and multiphoton microscopy with inertia-free laser scanning. However, all of the systems developed so far restrict fast imaging to two dimensions. This severely limits the extent to which neurons can be studied, as they represent complex three-dimensional structures. Here we present a new imaging system that utilizes a unique arrangement of acousto-optic deflectors to steer a focused, ultra-fast laser beam to arbitrary locations in three-dimensional space without moving the objective lens. As we demonstrate, this highly versatile random-access multiphoton microscope supports functional imaging of complex three-dimensional cellular structures such as neuronal dendrites or neural populations at acquisition rates on the order of tens of kilohertz.

Trigeminal and Glossopharyngeal Neuralgia

Trigeminal neuralgia and glossopharyngeal neuralgia are two causes of paroxysmal craniofacial pain. Either can be debilitating in affected individuals. This article reviews the epidemiology, pathogenesis, diagnosis, and treatment options for these disorders.

Percutaneous CT-guided cordotomy for the treatment of pediatric cancer pain.

Percutaneous cordotomy using CT guidance has been shown to be a safe and effective means of reducing pain in adults with cancer in 2 large case series. Its effectiveness in pediatric patients, however, has not been reported. Here, the authors present a case of CT-guided percutaneous cordotomy being used effectively for the treatment of unilateral limb pain in a 9-year-old boy suffering from metastatic medulloblastoma. The efficacy and minimally invasive nature of this procedure support its use in selected pediatric cases.

Eosinophilic granuloma/Langerhans cell histiocytosis: Pediatric neurosurgery update

Case 1 A 23‐month‐old female was admitted to the neurosurgery service with a 3‐month history of a progressively enlarging neck mass. There was associated redness, swelling, and tenderness to palpation, but no neurological deficits on examination. A noncontrast computed tomography (CT) scan of the neck and magnetic resonance imaging (MRI) with contrast showed an osteolytic contrast‐enhancing lesion primarily involving the C2 posterior elements, with a compressive circumferential epidural component extending from C2 to C5 [Figure 1]. A skeletal survey was negative for any other osseous lesions. She underwent C2 to C5 laminectomy with partial resection of the lesion without complication. Pathology was consistent with Langerhans cell (LC) histiocytosis (LCH). She was discharged home several days after her operation and subsequently started outpatient chemotherapy with cytarabine.

Revision surgeries following vagus nerve stimulator implantation

The vagus nerve stimulator (VNS) has been shown to provide a safe, albeit costly, treatment for intractable epilepsy. We aimed to analyze the incidence, timing, and clinical/demographic associations of revision surgery post-VNS implantation in epilepsy patients. The Thomson Reuters MarketScan database, containing data from 23-50million individuals, was used. Epilepsy patients receiving VNS implantations from 2003 to 2009 were identified by Current Procedural Terminology and International Classification Of Diseases Ninth Revision codes. Incidence and timing of subsequent implant-related surgeries were recorded. Events were described using time-to-event methodology, with Kaplan-Meier failure estimation/Cox proportional hazard models adjusted for clinical/demographic factors. In 1234 patients, average incidence of revision surgeries over 6years of follow-up were <1%, <3%, 4-10%, and <1% for VNS electrode revision, battery revision/removal, battery replacement/implantation, and infection washout, respectively. For electrode revision and battery revision/replacement, the incidence was higher in the first year and for battery replacement in later years. Age, sex, insurance type, or geographic region did not significantly impact event occurrence. Implant-related revision surgeries are rare. Some events occur more often in certain follow-up years than others; none are significantly impacted by age, sex, insurance type, or geographic region. The most common reason for revision was battery replacement several years after VNS placement.

Treatment options for pediatric craniopharyngioma.

Case 1 A 13‐year‐old female with intermittent headaches evaluated by an ophthalmologist was noted to have a retinal abnormality, prompting a magnetic resonance imaging (MRI) scan and referral to the neurosurgery service. On initial exam, the patient was neurologically intact and without headache. Imaging revealed a complex heterogeneous cystic mass, arising from a suprasellar location, invading into the third ventricle, and closely apposed to the hypothalamus bilaterally. There was mild contrast enhancement peripherally and inferiorly. Of note, the initial MRI and clinical presentation [Figure 1] showed no hydrocephalus. Likewise, initial endocrine evaluation was normal. On follow‐up imaging, however, the ventricular system was noted to be enlarging. After extensive discussion of the risks, benefits, and alternatives to surgery, a right frontal endoscopic transventricular resection was planned with a goal of gross total resection (GTR). Intraoperatively, the tumor was found to be densely adherent to the walls of the third ventricle. Approximately 50% of the tumor could be safely debulked. Postoperatively, she was noted to have hypopituitarism and required hormonal replacement with desmopressin, hydrocortisone, and levothyroxine. The patient was discharged in stable condition but returned soon after with symptoms and imaging consistent with a trapped right ventricle for which she underwent a septostomy and eventual ventriculoperitoneal shunt placement. She subsequently completed proton radiation for the residual tumor, which has remained stable over 4‐year follow‐up. After radiation, she developed hypothalamic obesity and suffered a gradual decline in her vision bilaterally. At last follow‐up, she could count fingers on the right and could only detect motion on the left. Since completing her treatments, she has required 24‐h care. The patient has had multiple emergency room visits and hospital admissions for sodium fluctuations. She has also suffered multiple bone fractures secondary to osteoporosis from chronic steroid use.

Management of hydrocephalus in children with posterior fossa tumors.

Case 1: A 2-year-old male with no prior medical history presented to the emergency room with a 3-week history of constant headache and daily vomiting. Computed tomography (CT) and subsequent magnetic resonance imaging (MRI) of the brain [Figure 1] showed a minimally enhancing mass in the fourth ventricle, which extended out through the foramen of Luschka on the left. There was associated supratentorial hydrocephalus. He had no evidence of spinal metastasis on MRI of the spine. There was no papilledema on the fundoscopic exam. He underwent placement of a right frontal external ventricular drain (EVD) and gross total resection of the tumor through a modified telovelar approach at the same time. The pathology was consistent with a grade II ependymoma. Postoperatively, the ventricular drain was unable to be weaned, and he underwent ventriculoperitoneal shunt placement without complication 1.5 weeks after initial surgery. He was eating and ambulatory after recovery. He went on to radiation therapy. Figure 1 Magnetic resonance images of patient described in case 1. (a) Sagittal precontrast. (b) Axial fluid-attenuated inversion recovery. (c) Axial postcontrast Case 2: A 9-year-old male with no prior medical history presented to an outside hospital emergency room with 2 weeks of progressive headaches and 1-day of vomiting. A CT of the head showed a posterior fossa mass. MRI of the brain [Figure 2] showed an enhancing fourth ventricular tumor with associated metastatic lesions throughout both cerebellar hemispheres and supratentorial hydrocephalus. There was no evidence of spinal metastasis. Fundoscopic exam was positive for papilledema. He underwent placement of a right frontal EVD and resection of the fourth ventricular mass through a modified telo-velar approach at the same time. The infiltrative lesions in the cerebellum were not resected. The pathology was consistent with medulloblastoma. Postoperatively, his EVD was weaned over the course of 2 weeks and removed. He did not require permanent cerebrospinal fluid diversion. He was discharged home after recovery and went on for adjuvant radiation therapy. Figure 2 Magnetic resonance images of patient described in case 2. (a) Sagittal precontrast. (b) Axial fluid-attenuated inversion recovery. (c) Axial postcontrast

Random-Access Multiphoton Microscopy for Fast Three-Dimensional Imaging

Studies in several important areas of neuroscience, including analysis of single neurons as well as neural networks, continue to be limited by currently available experimental tools. By combining molecular probes of cellular function, such as voltage-sensitive or calcium-sensitive dyes, with advanced microscopy techniques such as multiphoton microscopy, experimental neurophysiologists have been able to partially reduce this limitation. These approaches usually provide the needed spatial resolution along with convenient optical sectioning capabilities for isolating regions of interest. However, they often fall short in providing the necessary temporal resolution, primarily due to their restrained laser scanning mechanisms. In this regard, we review a method of laser scanning for multiphoton microscopy that overcomes the temporal limitations of pervious approaches and allows for what is known as 3D Random Access Multiphoton (3D RAMP) microscopy, an imaging technique that supports full three dimensional recording of many sites of interest on physiologically relevant time scales.

High-Speed Two-Photon Imaging

The small size of neuronal dendrites and spines combined with the high speed of neurophysiological signals, such as transients in membrane potential or ion concentration, necessitates that any functional study of these structures uses recording methods with both high spatial and high temporal resolutions. In this regard, conventional two-photon microscopy, in combination with fluorescent indicators sensitive to physiological parameters, has proved to be only a partial solution by providing near-diffraction-limited spatial resolution even when imaging structures deep inside light-scattering tissue. This is because the relatively slow beam-scanning methods used in most conventional two-photon microscopes severely limit the extent to which functional data can be recorded. Here, we detail developments to create high-speed two-photon imaging systems that overcome this limitation and discuss important considerations that must be taken into account when attempting to construct such systems.

Constriction band at the craniocervical junction in Maroteaux-Lamy syndrome

A 13-year-old girl with a history of mucopolysaccharidosis (MPS) type VI (Maroteaux-Lamy syndrome) presented to our clinic with a progressive history of spastic quadriparesis after a suboccipital craniectomy and C1 laminectomy for bony decompression of the craniocervical junction and concurrent occipitocervical fusion. Magnetic resonance imaging (MRI) workup is shown in Fig. 1. She underwent a re-do surgery, including intradural exploration to lyse a meningeal constriction band around the cervicomedullary junction (Fig. 2). Spinal cord compression is one of the major clinical complications of Maroteaux-Lamy syndrome [1–3]. Abnormal storage of glycoaminoglycans occurs in the dura mater, meninges, and supporting ligaments. In cases such as the present report, we recommend decompression (both extradural and intradural) and concurrent occipitocervical fusion (or, in cases of unfavorable bony cervical anatomy, occipitocervicothoracic fusion) with spinal instrumentation.