Kalai A. Muthusamy

Anatomy, physiology, and pathophysiology of the pedunculopontine nucleus.

The pedunculopontine nucleus is composed of cholinergic and non‐cholinergic neurones and is located in the caudal pontomesencephalic tegmentum. Evidence suggests that the nucleus plays a role in the production and control of movement. The nucleus has dense interconnections with the basal ganglia, as well as with other areas of the brain associated with motor control. Electrical stimulation of the pedunculopontine nucleus in the decerebrate cat or rat produces organized locomotor movements. Physiological studies show that the pedunculopontine nucleus modulates its activity in response to locomotion, as well as voluntary arm and eye movements. Degeneration of the pedunculopontine nucleus is seen in post‐mortem brains in humans with Parkinsons disease and Parkinsonian syndromes. In animal models of Parkinsons disease, metabolic changes are seen in the pedunculopontine nucleus, and chemical inhibition or mechanical disruption of the nucleus can produce an akinetic state in animals and man. In this paper we review the literature in support of the suggestion that some of the symptoms of Parkinsons disease are caused by dysfunction of the pedunculopontine nucleus. In accordance with this view, direct stimulation of the nucleus can ameliorate some symptoms of the disease, as demonstrated in both experimental animals and man.

Connectivity of the human pedunculopontine nucleus region and diffusion tensor imaging in surgical targeting

OBJECT The pedunculopontine nucleus (PPN) region of the brainstem has become a new stimulation target for the treatment of gait freezing, akinesia, and postural instability in advanced Parkinson disease (PD). Because PD locomotor symptoms are probably caused by excessive gamma-aminobutyric acidergic inhibition of the PPN, low-frequency stimulation of the PPN may overcome this inhibition and improve the symptoms. However, the anatomical connections of this region in humans are not known in any detail. METHODS Diffusion weighted magnetic resonance (MR) images were acquired at 1.5 teslas, and probabilistic tractography was used to trace the connections of the PPN region in eight healthy volunteers. A single seed voxel (2 x 2 x 2 mm) was chosen in the PPN just lateral to the decussation of the superior cerebellar peduncle, and the Diffusion Toolbox of the Oxford Centre for Functional Magnetic Resonance Imaging of the Brain was used to process the acquired MR images. The connections of each volunteers PPN region were analyzed using a human brain MR imaging atlas. RESULTS The PPN region was connected with the cerebellum and spinal cord below and to the thalamus, pallidum, subthalamic nucleus, and motor cortex above. The regions of the primary motor cortex that control the trunk and upper and lower extremities had the highest connectivity compared with other parts of motor cortex. CONCLUSIONS These findings suggest that connections of the PPN region with the primary motor cortex, basal ganglia, thalamus, cerebellum, and spinal cord may play important roles in the regulation of movement by the PPN region. Diffusion tensor imaging tractography of the PPN region may be used preoperatively to optimize placement of stimulation electrodes and postoperatively it may also be useful to reassess electrode positions.

Deep brain stimulation of the pedunculopontine nucleus in Parkinson's disease. Preliminary experience at Oxford.

Deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN) is a novel neurosurgical therapy developed to address symptoms of gait freezing and postural instability in Parkinsons disease and related disorders. Here, we summarize our non-human primate and neuroimaging research of relevance to our surgical targeting of the PPN. We also describe our clinical experience of PPN DBS with greatest motor improvements achieved by stimulation at low frequencies.

Neurosurgical endoscopic training via a realistic 3- dimensional model with pathology.

Introduction Training in intraventricular endoscopy is particularly challenging because the volume of cases is relatively small and the techniques involved are unlike those usually used in conventional neurosurgery. Present training models are inadequate for various reasons. Using 3-dimensional (3D) printing techniques, models with pathology can be created using actual patient’s imaging data. This technical article introduces a new training model based on a patient with hydrocephalus secondary to a pineal tumour, enabling the models to be used to simulate third ventriculostomies and pineal biopsies. Methods Multiple models of the head of a patient with hydrocephalus were created using 3D rapid prototyping technique. These models were modified to allow for a fluid-filled ventricular system under appropriate tension. The models were qualitatively assessed in the various steps involved in an endoscopic third ventriculostomy and intraventricular biopsy procedure, initially by 3 independent neurosurgeons and subsequently by 12 participants of an intraventricular endoscopy workshop. Results All 3 surgeons agreed on the ease and usefulness of these models in the teaching of endoscopic third ventriculostomy, performing endoscopic biopsies, and the integration of navigation to ventriculoscopy. Their overall score for the ventricular model realism was above average. The 12 participants of the intraventricular endoscopy workshop averaged between a score of 4.0 to 4.6 of 5 for every individual step of the procedure. Discussion Neurosurgical endoscopic training currently is a long process of stepwise training. These 3D printed models provide a realistic simulation environment for a neuroendoscopy procedure that allows safe and effective teaching of navigation and endoscopy in a standardized and repetitive fashion.

Three-dimensional anatomical accuracy of cranial models created by rapid prototyping techniques validated using a neuronavigation station

In neurosurgery and ear, nose and throat surgery the application of computerised navigation systems for guiding operations has been expanding rapidly. However, suitable models to train surgeons in using navigation systems are not yet available. We have developed a technique using an industrial, rapid prototyping process from which accurate spatial models of the cranium, its contents and pathology can be reproduced for teaching. We were able to register, validate and navigate using these models with common available navigation systems such as the Medtronic StealthStation S7®.

Spectra of central nervous system melioidosis

Burkholderia pseudomallei infection of the central nervous system (CNS) is rare with less than 50 cases reported over the last 30 years. The retrospective melioidosis study at University Malaya Medical Centre has documented three cases of CNS melioidosis out of more than 160 cases of melioidosis since 1978. There were two patients with brain abscess and one with spinal epidural abscess. The predisposing factors were: one patient was an aboriginal farmer and the other two were diabetic. Their age ranged from 17 to 45 years. Prominent neurological features were limb weakness, cranial nerve palsy (6th and 7th) and visual disturbance. CT brain scan and MRI spine showed abscess formation, subdural collection, and spinal epidural collection, osteomyelitis of vertebra and occipital bone and also sagital sinus thrombosis. All these patients underwent surgical drainage leading to bacteriological diagnosis as well as appropriate long-term antibiotic therapy. All had good recovery at 6 months after completion of treatment.

A Review of Sleep and Its Disorders in Patients with Parkinson's Disease in Relation to Various Brain Structures

Sleep is an indispensable normal physiology of the human body fundamental for healthy functioning. It has been observed that Parkinsons disease (PD) not only exhibits motor symptoms, but also non-motor symptoms such as metabolic irregularities, altered olfaction, cardiovascular dysfunction, gastrointestinal complications and especially sleep disorders which is the focus of this review. A good understanding and knowledge of the different brain structures involved and how they function in the development of sleep disorders should be well comprehended in order to treat and alleviate these symptoms and enhance quality of life for PD patients. Therefore it is vital that the normal functioning of the body in relation to sleep is well understood before proceeding on to the pathophysiology of PD correlating to its symptoms. Suitable treatment can then be administered toward enhancing the quality of life of these patients, perhaps even discovering the cause for this disease.

A new modified speculum guided single nostril technique for endoscopic transnasal transsphenoidal surgery: an analysis of nasal complications

Abstract The endoscopic transnasal, transsphenoidal surgical technique for pituitary tumour excision has generally been regarded as a less invasive technique, ranging from single nostril to dual nostril techniques. We propose a single nostril technique using a modified nasal speculum as a preferred technique. We initially reviewed 25 patients who underwent pituitary tumour excision, via endoscopic transnasal transsphenoidal surgery, using this new modified speculum-guided single nostril technique. The results show shorter operation time with reduced intra- and post-operative nasal soft tissue injuries and complications.

A Review of the Pedunculopontine Nucleus in Parkinson's Disease

The pedunculopontine nucleus (PPN) is situated in the upper pons in the dorsolateral portion of the ponto-mesencephalic tegmentum. Its main mass is positioned at the trochlear nucleus level, and is part of the mesenphalic locomotor region (MLR) in the upper brainstem. The human PPN is divided into two subnuclei, the pars compacta (PPNc) and pars dissipatus (PPNd), and constitutes both cholinergic and non-cholinergic neurons with afferent and efferent projections to the cerebral cortex, thalamus, basal ganglia (BG), cerebellum, and spinal cord. The BG controls locomotion and posture via GABAergic output of the substantia nigra pars reticulate (SNr). In PD patients, GABAergic BG output levels are abnormally increased, and gait disturbances are produced via abnormal increases in SNr-induced inhibition of the MLR. Since the PPN is vastly connected with the BG and the brainstem, dysfunction within these systems lead to advanced symptomatic progression in Parkinsons disease (PD), including sleep and cognitive issues. To date, the best treatment is to perform deep brain stimulation (DBS) on PD patients as outcomes have shown positive effects in ameliorating the debilitating symptoms of this disease by treating pathological circuitries within the parkinsonian brain. It is therefore important to address the challenges and develop this procedure to improve the quality of life of PD patients.