Gilbert R. Gonzales

The impact of a comprehensive evaluation in the management of cancer pain

&NA; To evaluate the importance of a comprehensive evaluation in the management of patients with cancer pain, we surveyed 276 consecutive consultations (226 retrospectively and 50 prospectively) performed by the pain consultant at Memorial Sloan‐Kettering Cancer Center. For all consultations, the pain diagnosis, other medical and neurologic diagnoses, investigations and suggested therapeutic interventions were recorded. The pain consultation identified a previously undiagnosed etiology for the pain in 64% of patients in both surveys. Metastatic neoplasm was the most common lesion discovered. In addition, the prospective yielded new neurologic diagnoses in 36% of patients and an unsuspected infection in 4%. Eighteen percent of prospectively surveyed patients received radiotherapy, surgery or chemotherapy based on the findings of the pain consultant. These data confirm the importance of a comprehensive neuro‐oncologic evaluation in the management of cancer pain. An understanding of oncology, neurology and medicine is critical to assess and treat these patients.

Olanzapine in the management of cancer pain

In cancer patients, cognitive impairment, psychological distress, and anxiety may accompany and aggravate pain. Neuroleptics are frequently used to control these symptoms and may be used to treat pain that has been unresponsive to more conventional approaches. Because of prominent side effects of traditional neuroleptics and conflicting data regarding their analgesic efficacy, their use in the treatment of pain remains controversial. Olanzapine, an atypical neuroleptic, might offer advantages because of its safer side effect profile. It has also been shown to have an independent antinociceptive activity in animals. The use of olanzapine in the management of cancer pain has not been previously described. We prospectively collected the data on 8 cancer patients with severe pain, uncontrolled in spite of aggressive opioid titration, who received olanzapine to treat severe anxiety and mild cognitive impairment. Patients did not meet criteria for delirium and their cognitive impairment was defined as cognitive disorder not otherwise specified (NOS) according to DSM-IV. Patients received 2.5 to 7.5 mg of olanzapine daily. In all patients, opioid requirements had escalated rapidly prior to starting olanzapine. Levels of pain, sedation, and opioid use were measured 2 days before and 2 days after olanzapine was started. Cognitive state was assessed daily. All 8 patients had marked reduction of the daily pain scores. The average daily opioid use decreased significantly in all patients. Cognitive impairment and anxiety resolved within 24 hours of initiating olanzapine. In these 8 patients, decreased pain scores and opioid requirements may have resulted from improvement in cognitive function and the known anxiolytic effect of olanzapine. Other mechanisms may include independent or adjuvant analgesic effects of olanzapine. We conclude that olanzapine may be useful in the treatment of patients with uncontrolled cancer pain associated with cognitive impairment or anxiety. Further studies to evaluate possible analgesic effect of olanzapine are needed.

Central pain Diagnosis and treatment strategies

The pathophysiology of central pain (CP) remains poorly understood.The paucity of objective findings on clinical examination of some of these patients can add to the difficulty in establishing a concrete diagnosis of CP. A pathophysiologic conceptual framework has been established to provide guidance. The goal of treatment should be pain reduction rather than complete pain relief. Surgical procedures have been used for specific causes of CP, but no one surgical technique helps relieve pain over the long term in all CP patients. Likewise, no one pharmacologic agent is successful in all CP patients, and pain relief is often incomplete. Pharmacologic treatment may take the form of stepwise addition of various agents, the cornerstone of which are antidepressants, followed by anticonvulsants, opioids, and other drugs. If all standard pharmacologic treatments fail, treatment of psychological problems induced by chronic pain is necessary since depression and the risk of suicide are significant in patients with poorly controlled CP. NEUROLOGY 1995;45(suppl 9): S11-S16

Methadone Analgesia in Cancer Pain Patients on Chronic Methadone Maintenance Therapy

Methadone is currently best known for its use as the maintenance drug in opioid addiction. The main concern when using methadone for the treatment of pain is its long and unpredictable half-life, which is associated with the risk of delayed toxicity. This may result in side effects such as sedation and respiratory depression if careful titration and close observation of individual patient responses are not performed. For this reason, methadone is often viewed as a second line opioid, after other opioids with a more predictable dose-response have been tried. We report six patients with long-term exposure to methadone as a treatment for heroin dependency, who were also treated with methadone for cancer pain. The first five patients were at least partially refractory to the analgesic effects of opioids other than methadone. All six patients achieved analgesia without sedation or respiratory depression from aggressive upward methadone titration. Methadone analgesia can be considered early in the course of treatment of patients with chronic exposure to methadone who develop new or worsening pain requiring opioid therapy.

Audio-Visual Communication and Its Use in Palliative Care

The technology of telemedicine has been used for over 20 years, involving different areas of medicine, providing medical care for the geographically isolated patients, and uniting geographically isolated clinicians. Today audio-visual technology may be useful in palliative care for the patients lacking access to medical services due to the medical condition rather than geographic isolation. We report results of a three-month trial of using audio-visual communications as a complementary tool in care for a complex palliative care patient. Benefits of this system to the patient included 1) a daily limited physical examination, 2) screening for a need for a clinical visit or admission, 3) lip reading by the deaf patient, 4) satisfaction by the patient and the caregivers with this form of communication as a complement to telephone communication. A brief overview of the historical prospective on telemedicine and a listing of applied telemedicine programs are provided.

Central pain in cancer patients

The prevalence of pain caused by injury to the central nervous system (CNS), or central pain (CP), in cancer patients is unknown. In order to define prevalence and characteristics of central pain in hospitalized patients with cancer, we performed a retrospective review of medical records of patients evaluated by 2 different services: the Pain Service and the Neurology Service, at Memorial Sloan-Kettering Cancer Center. The prevalence of CP in these patients was 4% and 2%, respectively. Primary and metastatic tumors and their therapy, including surgery, radiation and chemotherapy, were all potential causes of CP. The occurrence of CP in patients with primary CNS tumors was higher in patients with spinal cord tumors compared to patients with brain tumors (P <.0001).

Microelectrical Mechanical Systems Actuator Array for Tactile Communication

Tactile perception of alpha-numerics is possible using a tactile illusion (TI). The illusory sensation of motion is produced by mechanical actuators applying points of pressure on the skin. Vibrating points induce a nonveridical perception of motion from point to point. Intact lemniscal and parietal cortex are necessary for perception of the TI and can be used as a neurophysiological testing tool and an additional human-machine communication channel. We describe a 4 × 5 actuator array of individual vibrating pixels for fingertip tactile communication. The array utilizes novel micro-clutch MEMS technology. Individual pixels are turned ON and OFF by pairs of microscopic thermal actuators, while the main vibration is generated by a vibrating piezo-electric plate. Physiological parameters required for inducing TI and the fabrication sequence for the thermal micro-actuators along with actuation results are presented. Fingertip perception of micro-actuators could be built into a variety of data acquisition interfaces for handicapped persons.

Epidural air from a bronchopleural-epidural-cutaneous fistula producing reversible myelopathy and radiculopathy symptoms

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Fingertip communication: A tactile communication device for a glove

Tactile communication is possible using a phenomenon known as a tactile illusion (TI). Illusion of movement on the skin is produced through fixed vibrating points (actuators) using parameters including vibration on- and off-time, number of vibrations, and intervibrating point time delays. Multiple actuators (solenoids) can produce the TI of movement between actuators that are sequentially activated to produce the illusion of motion on the skin. This illusion of movement can be made to form alphanumerics perceived on the fingertip that will allow for an alternate method of communication to auditory or visual receptive communications. A thimble is designed using piezoelectric bimorphs (piezo) or microelectromechanical systems (MEMS) to produce alphanumerics in the glove of a flight or space suit and on control surfaces, for immediate feedback communications. Solenoid devices have been made and tested and background research has been completed to aid in the design and production of piezo and MEMS fingertip d...

HUMAN BRAIN DOSIMETRY IN DISRUPTED BLOOD BRAIN BARRIER (BBB) USING [SN-117M]-DOTA-ANNEXIN V (SNDAV): A MODEL FOR TARGETING AGED MICROGLIA IN ALZHEIMER'S DISEASE

P4-017 HUMAN BRAIN DOSIMETRY IN DISRUPTED BLOOD BRAIN BARRIER (BBB) USING [SN-117M]DOTA-ANNEXIN V (SNDAV): A MODEL FOR TARGETING AGED MICROGLIA IN ALZHEIMER’S DISEASE Gilbert R. Gonzales, Nigel R. Stevenson, Cynthia A. Doerr, George Sgouros, H. William Strauss, NeuroSn, Inc., Tucson, AZ, USA; Johns Hopkins University, Baltimore, MD, USA; Memorial Sloan-Kettering Cancer Center, New York, NY, USA. Contact e-mail: ggonzales@r-nav.com Background:Microglia, the macrophages of the brain, are a potential target for treatment based on the neuroinflammatory hypothesis of Alzheimer’s Disease (AD). Annexin V binds to the outer leaflet of the cell membrane of cells undergoing apoptosis. Previous studies utilizing Sn-117m chelated to annexin V [SnDaV] demonstrated localization in atheroma containing macrophages. Human stroke subjects were injected intravenously with SnDaV in order to target apoptosis in carotid artery macrophages,. The dose of radiation delivered to the macrophages can itself induce apoptosis. Sn-117m is a radionuclide with a 14 day half-life that emits both imaging gamma rays and therapeutic conversion electrons (CE). Methods: Sn-117m was coupled to aminobenzylDOTA and purified using HPLC. Conjugation of the chelate to annexin V-128 was accomplished by preparing the isothiocyanate version of the chelate and then reacting it with lysine residues on the annexin for 90 mins at 37 C. Analytical methods were used to evaluate the cGMP SnDaV that was produced. The product was >95% monomer; cell binding results were typically pK1⁄42325. Overall chelation yields werew95% andw40% for conjugation to the annexin V. Subjects with symptomatic carotid stenosis and ischemic signs who were scheduled to undergo carotid endarterectomy were given an intravenous dose of SnDaV prior to surgery. Brain dosimetry was determined by employing HERMES image analysis software to calculate the organ activity at various time points. Results: SnDaV resided in the brain of human poststroke subjects, delivering gamma photons and therapeutic CE for up to 500 hours. We were able to determine that SnDaV was bound to and slowly released from the brain and resided in the brain long enough to potentially provide a therapeutic effect for up to 21 days. Conclusions:We have demonstrated that systemically delivered SnDaV resides in the brain of subjects with ischemia-disrupted BBB. We hypothesize that SnDaV may be used to suppress aged microglia as a novel AD amyloid and tau therapeutic. References: 1. Microglia and brain macrophages in the molecular age: from origin to neuropsychiatrie disease. Marco Prinz and Josef Priller. Nature Reviews Neuroscience Volume: 15, Pages: 300–312 Year published; 2014. 2. Microglia and macrophages of the central nervous system: the contribution of microglia priming and systemic inflammation to chronic neurodegeneration. V. Hugh Perry& Jessica Teeling. Semin Immunopathol 35:601–612. 3. Tin-117m-DOTA-Annexin for Imaging and Treating Vulnerable Plaque. Gilbert Gonzales, ICRT WARMTH, Finland, 2012. 4. Simultaneous imaging and treatment of vulnerable plaques with tin-117m-DOTA-Annexin. Srivastava SC, Narula J, Strauss HW, Gonzales GR. 2nd International Workshop on Innovative Personalized Radio-immunotherapy, WIPR 2013. Nantes, France. July 9–12, 2013. 5. Proliferating culture of agedmicroglia for the study of neurodegenerative diseases. Rommy von Bernhardi, Juan Tichauer, Laura Eugenin-von Bernhardi. Journal of Neuroscience Methods 202 (2011) 65–69. 6. Microglial aging in the healthy CNS: phenotypes, drivers and rejuvenation. Frontiers in Cellular Neuroscience. Review Article. Published 13 March 2013. Article 7, volume 22; 160–172. Wai T. Wong. 7. Depletion of microglia and inhibition of exosome synthesis halt tau propagation. Hirohide Asai, Seiko Ikezu, Satoshi Tsunoda, Maria Medalla, Jennifer Luebke, Tarik Haydar, BenjaminWolozin, Oleg Butovsky, Sebastian K€ugler & Tsuneya Ikezu. Nature Neuroscience, published online 5 October 2015; http://dx.doi.org/10.1038/nn.4132.