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Deep Brain Stimulation for Epilepsy

Introduction Epilepsy is a chronic seizure condition, classically characterized as “a continuing tendency to seizure relapse” ( ). It was estimated to affect 50 million people worldwide in 2012. As a chronic condition, epilepsy confers significant mortality, including suicide and SUDEP (sudden unexpected death in epilepsy patients) ( ), and morbidity, including cognitive, psychological, and social impairment, risk of injury, and socioeconomic consequences ( ). While…

Vagal Nerve Simulation

Vagus nerve stimulation (VNS) delivered via the implantable Neurocybernetic Prosthesis (NCP) from LivaNova PLC (London, United Kingdon) is an established treatment option for patients with intractable epilepsy. It has also emerged as a novel adjunct in the management of patients with refractory depression and potentially other disorders. Since the first implantation in 1988 more than 80,000 patients worldwide have received VNS therapy. The NCP device delivers…

Epilepsy: Anatomy, Physiology, Pathophysiology, and Disorders

Introduction The first description of an epileptic seizure was written in Akkadian, the oldest written language, which dates from about 3000 years ago in Mesopotamia. The seizure was attributed to the god of the moon. Further anecdotal cases of epilepsy were found in Egyptian, Chinese, Indian, and Babylonic writings ( ). In ancient history epilepsy was believed to be caused by spirits or gods. In 400…

Infusion Therapy for Movement Disorders

Review of the Current Knowledge Base of the Topic Direct intracerebral infusion of neurotrophic factors may represent a neuroprotective and neurorestorative therapeutic strategy for neurodegenerative movement disorders, most notably Parkinson’s disease (PD). A number of neurotrophins, including glial cell-line-derived neurotrophic factor (GDNF), neurteurin (NTN), cerebral dopamine neurotrophic factor (CDNF), and mesencephalic astrocyte-derived neurotrophic factor (MANF), are currently under preclinical and clinical investigation as infusional therapies for…

Deep Brain Stimulation of the Pedunculopontine Tegmental Nucleus Improves Static Balance in Parkinson’s Disease

Acknowledgments This work was partly supported by small RIA grants (2014–2015) from University of L’Aquila. Introduction Postural instability is a severe symptom in Parkinson’s disease (PD) and atypical Parkinsonisms that causes falls and postural deformities ( ). The treatment of postural instability in PD with antiParkinsonian drugs is unsatisfactory, and frequent falls occur in patients who experience good pharmacological control of other motor disabilities ( ).…

Surgical Management of Hemifacial Spasm and Meige Syndrome

Hemifacial Spasm Introduction Hemifacial spasm (HFS) is a unilateral, involuntary, paroxysmal movement of facial muscles innervated by the ipsilateral facial nerve. Its characteristic features include tonic–clonic contractions and synkinesis of the muscles. These symptoms usually start from the orbicularis oculi muscle and gradually spread inferiorly to the muscles around the cheek, mouth, and neck. Eventually the facial spasm worsens in frequency and severity, resulting in sustained…

Deep Brain Stimulation in Tourette Syndrome

Introduction Diagnosis and Prevalence Tourette syndrome (TS) is a chronic neuropsychiatric disorder with an unknown etiology characterized by motor and vocal tics. The onset of tics occurs most commonly in early childhood around the age of 5–7 years, and the disorder follows a typical waxing and waning pattern over the years ( ). The severity and frequency of tics increase during the prepubescent years and decline…

Deep Brain Stimulation for Dystonia

Acknowledgment The senior author wishes to thank Donald Weisz, PhD for his assistance with the production of Fig. 76.3 , for his friendship, and for his passionate commitment to patient care. Introduction Dystonia is a neurological disorder characterized by sustained or intermittent muscle contractions causing twisting, repetitive movements that result in abnormal, often painful, postures ( ). Different muscle groups may be involved to a variable…

Deep Brain Stimulation for Tremor

Historical Perspective Tremor, the involuntary and rhythmic oscillation of a body part, is classified according to its presumed etiology, or alternatively by its phenomenology (description of the affected body area, frequency, and condition in which it manifests). Common tremor conditions include essential tremor (ET), Parkinson’s disease (PD), dystonic tremor, cerebellar tremor, Holmes tremor, physiologic and enhanced physiologic tremor, palatal tremor, neuropathic tremor, drug/toxin-induced tremors, and psychogenic…

Deep Brain Stimulation in Parkinson’s Disease

Introduction Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the cardinal motor features: rest tremor, bradykinesia, rigidity, and loss of postural reflexes. The pathological hallmark of PD is degeneration of dopaminergic neurons in the substantia nigra pars compacta and the presence of alpha synuclein positive neuronal inclusions known as Lewy bodies. It is the second most common neurodegenerative disorder, following Alzheimer’s disease. In the…

Deep Brain Stimulation for Pain

Relevant History of the Topic Including Developments Over the Past Decade The application of neurostimulation to the management of chronic pain syndromes remains a significant challenge for chronic pain specialists. The origins of deep brain stimulation for intractable pain can be traced back to rodent studies in the 1950s. James Olds and Peter Milner implanted electrodes into various targets in the rodent brain, and found such…

Intrathecal Baclofen Therapy for the Control of Spasticity

Introduction Intrathecal baclofen therapy (IBT) has been used for 3 decades in the management of spastic hypertonia associated with the upper motor neuron syndrome ( ). This chapter will describe patient selection, initial trialing, management of the newly implanted patient, chronic maintenance therapy, and management of intrathecal (IT) baclofen overdose and withdrawal. As of 2016 only one manufacturer (Medtronic) has United States Food and Drug Administration…

Compounding for Intrathecal Analgesic Agents

Introduction From a historical standpoint, pharmaceutical compounding dates back 5000 years. The practice of apothecary is mentioned in the Bible as a trade. Apothecaries or physicians would compound oils, powders, aromatics, and elixirs to treat various medical conditions. Many compounds were extracted from animals and plants, such as opium. Throughout the 19th and 20th centuries pharmacists and physicians provided numerous compounded preparations to treat their patients.…

The Development of Guidelines for Intrathecal Therapies for Pain Control. History and Present Guidelines

Introduction The use of intrathecal (IT) therapies for the control of chronic pain has become an important part of the treatment algorithm for those who suffer with chronic disease. In the effort to control suffering, these therapies have been used in different clinical settings with varying degrees of success. The approval of IT morphine by the United States Food and Drug Administration (FDA) led to the…

Potent Neurotoxins for Cancer Pain Treatment: Resiniferatoxin and Saporin

Introduction Intractable cancer pain continues to be a significant issue for oncological care. Although the spread of the disease may be controlled, symptom management for nausea, vomiting, lack of appetite, and pain control can be elusive. Interventional treatments, such as intrathecal (IT) neurolysis, may need to be utilized once conventional systemic therapies have been tried and failed. IT neurolytic blockade to the sympathetic chain and spinal…

Exploring Nonopioid Analgesic Agents for Intrathecal Use

Introduction Intrathecal drug delivery systems (IDDSs) for chronic pain work by delivering a solution of an analgesic compound directly into the cerebrospinal fluid (CSF) for greater analgesic efficacy and minimal side-effects, as opposed to administering it through the systemic route. This mode of therapy has been in use for more than 30 years, but to this day only two analgesic compounds, morphine (Infumorph) and ziconotide (Prialt),…

Cerebrospinal Fluid Dynamics and Intrathecal Delivery

Introduction This chapter reviews the relationships between cerebrospinal fluid (CSF) dynamics and drug biodistribution following intrathecal (IT) administration. We attempt to provide the reader with a very thorough state-of-the-art review of the assessment of CSF dynamics that occurs with natural pulsations inside the spinal and cranial subarachnoid spaces (SAS). CSF dynamics are important because the fluid flow patterns significantly determine the biodistribution of IT delivery. Specifically…

Pharmacology of Intrathecal Therapy

Introduction The history of intrathecal (IT) implantable drug delivery system (IDDS) therapy for chronic cancer and noncancer pain is rooted in experimentation with local anesthetics administered into the cerebrospinal fluid (CSF). For a thorough historical review see Chapter 60 . Since the first implantable pumps were approved by the United States Food and Drug Administration (FDA), experience with more than 300,000 implanted pumps has established IDDS…

Evolution of the Spinal Delivery of Opiate Analgesics

Introduction The systematic study of spinal systems and their transmitter biology has shown them to play a defining role in the encoding of afferent input and the tuning of autonomic and somatomotor outflow. Studies on the pharmacology of these spinal linkages have revealed that drugs with an action limited to the spinal cord can have surprisingly robust but selective effects upon behaviorally relevant components, including pain…

Relevant Anatomy for Spinal Drug Delivery

Introduction Neuromodulation is an important therapy that modulates/modifies neural responses to a neural stimulus so the body has a different response at the peripheral, spinal, or brain level. Neuromodulation can be performed by electrical stimulation or by drug delivery. Intrathecal drug delivery systems (IDDS) allow for continuous and targeted delivery of medications to the spinal cord to treat chronic refractory pain or spasticity ( ). Appropriate…