The document discusses efficacy and tolerability of newer antiepileptic drugs based on numerous studies. It summarizes that lamotrigine is effective for initial monotherapy in new onset partial seizures in adults and children, and as add-on therapy for refractory partial epilepsy. Topiramate is effective as add-on therapy for refractory partial seizures in adults and children, and for monotherapy in refractory partial seizures and idiopathic generalized tonic-clonic seizures. Both drugs show efficacy in Lennox-Gastaut syndrome but may worsen myoclonic seizures. Tolerability varies with dose and titration speed.
New Treatment Devices and Clinical Trials jgreenberger
Dr. Kathryn Davis from Penn Epilepsy Center present on new treatment devices and clinical trials for epilepsy. From the 2014 Epilepsy Education Exchange.
New Treatment Devices and Clinical Trials jgreenberger
Dr. Kathryn Davis from Penn Epilepsy Center present on new treatment devices and clinical trials for epilepsy. From the 2014 Epilepsy Education Exchange.
Epilepsy is the disease which has prevalence in India more than 1 %
Of population. This is topic of research for young medicine practioner and pharmacist.
This interesting ppt deals with the Pharmacology of Antiepileptic drugs and the treatment of different types of seizures with beautiful illustrations....
Treatment of epilepsy polytherapy vs monotherapyPramod Krishnan
This presentation reviews the evidence regarding use of early polytherapy in patients with epilepsy with regards to seizure control and adverse effects. The advantages and disadvantages of polytherapy compared to monotherapy is addressed.
Epilepsy is the disease which has prevalence in India more than 1 %
Of population. This is topic of research for young medicine practioner and pharmacist.
This interesting ppt deals with the Pharmacology of Antiepileptic drugs and the treatment of different types of seizures with beautiful illustrations....
Treatment of epilepsy polytherapy vs monotherapyPramod Krishnan
This presentation reviews the evidence regarding use of early polytherapy in patients with epilepsy with regards to seizure control and adverse effects. The advantages and disadvantages of polytherapy compared to monotherapy is addressed.
A guideline for discontinuing antiepileptic drugs in seizure-free patients – ...Dr. Rafael Higashi
Aula apresentada por Dr. Rafael Higashi, médico neurologista sobre quando retirar droga antiepilética. A guideline for discontinuing antiepileptic drugs in seizure-free patients – Summary Statement
A review of the common antiseizure drugs with broad spectrum action. We look at the major evidence in favour of valproate, topiramate, perampanel and brivaracetam.
A review of literature about Stiripentol and Rufinamide and their role in Dravets and Lennox Gastaut Syndrome respectively. It also looks at off label indications of these two orphan drugs.
Treatment Options for Drug-Resistant Epilepsy
In some people with drug resistant epilepsy, there are effective treatment options, with a high chance of seizure freedom. These include:
Resective Epilepsy Surgery
Resective epilepsy surgery consists of removing the area of the brain that is causing the seizures. However, for a patient to be a good candidate for surgery, the following conditions have to be met:
The area of the brain where seizures originate is clearly identified.
That area of the brain can be safely removed with surgery. In other words if the risk is greater than “minimal risk,” the patient is not a candidate.
The probability to achieve seizure freedom with epilepsy surgery varies depending on the structures of the brain involved. For example, patients whose seizures originate in the temporal lobe have a 50% to 70% chance of achieving seizure-freedom.
Today, newer, less-invasive techniques are being used in the place of resective surgery in appropriate cases. These include the use of laser, in which a laser probe burns the area of the brain causing the seizures. However, these new techniques may not work for all candidates for resective surgery.
Specific Metabolic Treatment
While metabolic causes of epilepsy are uncommon, identifying some of these conditions can lead to specific treatments to allow the body to compensate for the metabolic change.
Examples are treatment with a ketogenic diet for GLUT1 deficiency, treatment with pyridoxine or pyridoxal-5-phosphate for vitamin dependent epilepsies, and creatine supplementation for creatine deficiency syndromes.
Specific Genetic Causes
Identifying a specific genetic cause can help your doctor choose the best treatment for seizures.
For example, with SCN1A pathogenic variants, medications such as Oxcarbazepine (Trileptal), Carbamazepine (Tegretol) or Phenytoin (Dilantin) should be avoided. Whereas with other types of pathogenic variants, such as SCN2A and SCN8A variants, these medications can be very helpful.
Some specific treatments which target the underlying problem caused by the genetic variant are in clinical trials, and may improve learning and development as well as help with seizures.
Immunotherapy
In the last decade, the role of inflammatory processes in certain types of epilepsy has been recognized. In these cases, medications that counteract these processes have been used with success. However, they have to be used with caution as they are associated with a variety of adverse events.
Management of locally advanced ovarian, fallopian tube, and peritoneal tumors requires a comprehensive and multidisciplinary approach. Locally advanced tumors are those that have spread beyond the ovaries or fallopian tubes and may involve nearby structures, such as the peritoneum or adjacent organs. Here's a brief overview of the management strategies:
Surgery:
Debulking Surgery: The primary treatment for locally advanced tumors involves cytoreductive or debulking surgery. This aims to remove as much of the tumor as possible. Surgeons may perform a total hysterectomy, bilateral salpingo-oophorectomy, and removal of involved peritoneal tissues.
Lymphadenectomy: Lymph node dissection is often done to assess the extent of the disease spread and to remove involved lymph nodes.
Chemotherapy:
Neoadjuvant Chemotherapy: In some cases, chemotherapy may be administered before surgery to shrink the tumor, making surgery more effective.
Adjuvant Chemotherapy: Following surgery, chemotherapy is typically recommended to target any remaining cancer cells. Platinum-based chemotherapy regimens are commonly used.
Targeted Therapies:
PARP Inhibitors: Poly (ADP-ribose) polymerase inhibitors, such as olaparib and niraparib, have shown efficacy in treating ovarian and related cancers with specific genetic mutations, like BRCA mutations.
Immunotherapy:
Checkpoints Inhibitors: Immune checkpoint inhibitors, like pembrolizumab and nivolumab, may be considered in cases with specific molecular profiles.
Radiation Therapy:
External Beam Radiation: In some situations, radiation therapy may be used to target specific areas affected by the tumor.
Clinical Trials:
Participation in clinical trials may be an option for patients with locally advanced disease, offering access to innovative treatments and therapies.
Follow-up Care:
Regular monitoring and follow-up care are crucial to assess treatment effectiveness and detect any signs of recurrence.
Palliative Care:
Palliative care should be integrated into the management plan to address symptom control, improve quality of life, and provide support for both the patient and their family.
A personalized treatment plan should be developed based on the specific characteristics of the tumor, the patient's overall health, and individual factors. Regular communication among a multidisciplinary team, including surgeons, medical oncologists, radiation oncologists, and other specialists, is essential for optimizing the management of locally advanced ovarian, fallopian tube, and peritoneal tumors.
Jorge A. Marrero, MD, MS, Anthony El-Khoueiry, MD, Richard S. Finn, MD, and Laura M. Kulik, MD, prepared useful practice aids pertaining to HCC management for this CME activity titled "Surveying the View From the Driver’s Seat in Hepatocellular Carcinoma: Bringing Into Focus Hepatology’s Key Role in Guiding HCC Care Down the Path to Improved Outcomes." For the full presentation, monograph, complete CME information, and to apply for credit, please visit us at http://bit.ly/2Pj9wM8. CME credit will be available until December 20, 2019.
Epilepsy Management: Key issues and challengesPramod Krishnan
This brief presentation summarises the key issues and challenges in Epilepsy management, including diagnosis, treatment, compliance, special populations, adverse effects, psychiatric comorbidities and ASM withdrawal.
This presentation focusses on the importance of diagnostic biomarkers for Alzheimer's disease. MRI, amyloid PET and CSF biomarkers are discussed in detail.
This presentation looks at the benign or non-epileptiform variants in EEG, their characteristics and identification. Examples of the common benign variants are provided in the presentation.
This presentation reviews the common artifacts in EEG, their identification and rectification. Examples of various artifacts are provided in the presentation.
This is a brief review of autoimmune epilepsies, especially autoimmune encephalitis, SREAT, NORSE, FIRES and Rasmussen's encephalitis. A brief overview of investigations and treatment is included.
This presentation looks at the role of Pregabalin in refractory trigeminal neuralgia and chemotherapy induced peripheral neuropathy through illustrative case studies.
This review focusses on the role of role of gut microbiota in health and disease, specifically multiple sclerosis. It looks at the interaction of gut microbiota, enteric nervous system, central nervous system, neuroendocrine system in the pathogenesis of multiple sclerosis
This presentation summarises the importance of genetics in epilepsy, whom to test, and the various tests available. It looks at the role of genetics in various forms of epilepsy and recent advances in precision medicine.
EEG in convulsive and non convulsive seizures in the intensive care unitPramod Krishnan
Case based discussion regarding the utility of EEG in the management of convulsive and non convulsive seizures, including status epilepticus in the intensive care unit
A review of epilepsy in the elderly, the etiopathogenesis, clinical challenges, diagnosis, use of antiseizure drugs and outcomes. Also the various special considerations in managing elderly patients with epilepsy.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
Muktapishti is a traditional Ayurvedic preparation made from Shoditha Mukta (Purified Pearl), is believed to help regulate thyroid function and reduce symptoms of hyperthyroidism due to its cooling and balancing properties. Clinical evidence on its efficacy remains limited, necessitating further research to validate its therapeutic benefits.
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
ABDOMINAL TRAUMA in pediatrics part one.drhasanrajab
Abdominal trauma in pediatrics refers to injuries or damage to the abdominal organs in children. It can occur due to various causes such as falls, motor vehicle accidents, sports-related injuries, and physical abuse. Children are more vulnerable to abdominal trauma due to their unique anatomical and physiological characteristics. Signs and symptoms include abdominal pain, tenderness, distension, vomiting, and signs of shock. Diagnosis involves physical examination, imaging studies, and laboratory tests. Management depends on the severity and may involve conservative treatment or surgical intervention. Prevention is crucial in reducing the incidence of abdominal trauma in children.
Local Advanced Lung Cancer: Artificial Intelligence, Synergetics, Complex Sys...Oleg Kshivets
Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Basavarajeeyam is an important text for ayurvedic physician belonging to andhra pradehs. It is a popular compendium in various parts of our country as well as in andhra pradesh. The content of the text was presented in sanskrit and telugu language (Bilingual). One of the most famous book in ayurvedic pharmaceutics and therapeutics. This book contains 25 chapters called as prakaranas. Many rasaoushadis were explained, pioneer of dhatu druti, nadi pareeksha, mutra pareeksha etc. Belongs to the period of 15-16 century. New diseases like upadamsha, phiranga rogas are explained.
Adv. biopharm. APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMSAkankshaAshtankar
MIP 201T & MPH 202T
ADVANCED BIOPHARMACEUTICS & PHARMACOKINETICS : UNIT 5
APPLICATION OF PHARMACOKINETICS : TARGETED DRUG DELIVERY SYSTEMS By - AKANKSHA ASHTANKAR
Integrating Ayurveda into Parkinson’s Management: A Holistic ApproachAyurveda ForAll
Explore the benefits of combining Ayurveda with conventional Parkinson's treatments. Learn how a holistic approach can manage symptoms, enhance well-being, and balance body energies. Discover the steps to safely integrate Ayurvedic practices into your Parkinson’s care plan, including expert guidance on diet, herbal remedies, and lifestyle modifications.
17. Mechanism of Action Deckers CLP et al. Epilepsia 2000; 41(11): 1364–1374. ++ Clobazam + + Zonisamide +++ Vigabatrin Binds to synaptic vesicle protein SV2A Levetiracetam +++ Tiagabine + + +++ Oxcarbazepine + ++ ++ Topiramate + +++ Lamotrigine + ++ + Gabapentin Antiglutamate GABA mimetic Non- T type Ca channel blockade Na channel blockade AED
18. Pharmacokinetics Panayiotopoulos CP. The Epilepsies: seizures, syndromes and management 24-60 4-7 4-9 6-8 15-23 15-30 4-6 Elimination t1/2 (hr) No No Renal 96% LEV No No Hepatic Clobazam Yes No Hepatic 40-60% Zonisamide No No Renal Vigabatrin Yes No Hepatic 40% Tiagabine Yes Ind, inh Hepatic 0% OXC Yes Ind, Inh Renal > H 9-17% Topiramate Yes Induction Hepatic 55% Lamotrigine No No Renal 0 Gabapentin Drug interactions Enzyme ind/inh Metabolism Protein binding AED
19. Practical Implications Panayiotopoulos CP. The Epilepsies: seizures, syndromes and management Not required Minimal 0-2 wks Yes Levetiracetam Not useful Minimal 4 wks No Clobazam Useful Maximal 4 wks Yes Zonisamide Not needed Maximal 4 wks No Vigabatrin Not required Minimal 4 wks No Tiagabine Not useful Maximal 4 weeks No Oxcarbazepine Useful Maximal 6 wks Yes Topiramate Very useful Maximal 8 wks Yes Lamotrigine Not required Minimal 0-2 wks No Gabapentin Drug monitoring Lab testing? Slow titration? Broad spectrum AED
21. New onset epilepsy Study 1: Pts aged 13-81 yrs with partial or primary generalized epilepsy Study 2: 150 elderly pts with mean age of 77 yrs 42% 18% Discontinuation No difference in the efficacy. Rash was more in the CBZ group 400-2000 mg/d 100-500 mg/d Dose Brodie MJ. Epilepsy Res 1999; 37: 81-87 Brodie MJ et al. Lancet 1995; 345: 476-9 13% 9% Rash 21% 11.5% Discontinuation 76% 78% Generalized seizures (n=122) 51% 48% Partial seizures (n=146) Seizure freedom CBZ (600 mg/d) LTG (150 mg/d) Dose
22. New onset epilepsy: Study 3 Steiner TJ et al. Epilepsia 1999; 40: 601-7 28% 7% Somnolence 29% 16% Asthenia 5% 14% Rash 11% 0 Ataxia Adverse effects 19% 15% Discontinuation 46% 45% Partial 36% 43% IGE Seizure freedom during last 24 weeks of therapy 46 pts 44 pts Partial 95 pts 86 pts IGE PHT LTG
25. Refractory partial epilepsy: Monotherapy Gilliam F et al. Neurology 1998; 51: 1018-25 Exit criteria: Increased duration of GTCS/ emergence of new, more severe seizure type Doubling of the highest 2 day consecutive seizure rate Doubling of baseline seizure frequency Outcome: proportion of pts meeting exit criteria during concomitant AED withdrawal or the 3 month maintenance period. 8% 11% Rash 5% 11% Discontinuation rate 57 days 168 days Median time to exit 20% 37% Completed study VPA (1000 mg/d) LTG (500 mg/d) Dose
26. Children: Refractory partial epilepsy Duchowny M et al. Neurology 1999; 53: 1724-31 LTG dose (mg/kg): 1-3 if given with VPA only, 1-5 if with VPA and enzyme inducing drugs, 5-15 if given with enzyme inducing drugs only. Asthenia Dizziness Nausea Ataxia 199 children between 2-16 yrs of age. Steven Johnson syndrome- I case Tremor Most common adverse effects 6% 5% Discontinuation rate 12.8% 44% Decrease in weekly seizure frequency 25% 45% 50% responder rate Placebo LTG
27. Lennox- Gastaut syndrome Motte J et al. N Eng J Med 1997; 337: 1807-12 Eriksson AS et al. Epilepsia 1998; 39: 495-501 Jansky J et al. Clin Neuropharmacol 2000; 23: 86-9 - 60% 50% responder rate Class II study: open label, followed by double blind phase. N=17 6% 5% Rash Dose ranged from 50-100 mg/d for pts < 25 kg on VPA to 300-400 mg/d for pts > 25 kg not on VPA. 18% 16% Discontinuation rate 16% 33% 50% responder rate for total seizures Class I study Worsening of myoclonic jerks was noted in a case report. 8% 4% Discontinuation rate Placebo LTG
28. Adverse effects Headache Somnolence Asthenia Rash Incidence of rash is more when added to CBZ containing regimens. Anorexia Incoordination Diplopia Dyspepsia Abdominal pain Vomiting Tremor Nausea Ataxia Dizziness
32. New onset epilepsy Privitera MD et al. Acta Neurol Scand 2003; 107: 165-75 No significant difference Time to first seizure 600 1250 200 100 Dose (mg/d) 613 pts with partial/primary generalized epilepsy, aged > 6 yrs 25% 23% 28% 19% Discontinuation rate No difference in efficacy between the 4 groups Proportion of seizure free pts for last 6 months of therapy: No significant difference No significant difference Time to exit CBZ VPA TPM TPM
33. Refractory partial epilepsy- adjunctive therapy Faught E et al. Neurology 1996; 46: 1684-90 Privitera M et al. Neurology 1996; 46: 1678-83 13% 47.8% 50% Responder rate No difference 50% Responder rate - 17% 10.5% 21% Discontinuation rate - 4% 9% 13% Discontinuation rate No improvement in efficacy at dose > 400 mg/d. Placebo 600 Study 3 Dose (mg/d) Placebo 1000 800 600 Study 2 Dose (mg/d) - 48% 49% 27% 50% Responder rate Placebo 200 400 600 Study 1 Dose (mg/d)
34. Refractory partial epilepsy: Monotherapy Sachdeo RC et al. Epilepsia 1997; 38: 294-300 Longer in pts on 1000 mg/d (p=0.002) Time to exit 8.3% 0 Discontinuation rate Similar but less frequent compared to add-on therapy Adverse effects 13% 0 100% seizure reduction 46% 13% 50% responder rate 62% 25% Completed study TPM (1000 mg/d) TPM (100 mg/d) N=100
35. Idiopathic refractory generalized epilepsy Biton V et al. Neurology 1999; 52: 1330-7 Age > 3 yrs with refractory GTCS, with or without other seizure types. Adverse effects were similar to other studies. 2.4% 2.6% Discontinuation rate 20% 56% 50% responder rate Placebo TPM (6 mg/kg/d) Dose One Class I study and ten Class IV studies
36. Children: Refractory partial epilepsy Elterman RD et al. Neurology 1999; 52: 1338-44 Arcas J et al. Epilepsia 2001; 42: 1363-5 Weight loss Difficulty in concentrating Memory deficits Emotional lability 86 children between 2-16 yrs of age, 16 week trial. Hypohidrosis Fatigue Most common adverse effects 2 children 0 Discontinuation rate 10.5% 33% Median reduction in seizures 20% 39% 50% responder rate Placebo TPM (125-400) Dose (mg/d)
37. Lennox- Gastaut syndrome Sachdeo RC et al. Neurology 1999; 52: 1882-7 Glauser TA et al. Epilepsia 2000; 41: S86-90 55% 50 % responder rate Above patients were followed up for 6 months Class I study 56% Median reduction in drop attacks Class IV study: open label 5.1% increase 14% decrease Drop attacks No significant difference 50% responder rate for total seizures Placebo TPM (6 mg/kg/d) Dose
38. Adverse effects Dizziness Psychomotor slowing Confusion Headache Slow titration led to less dose-related side-effects. Paresthesias Word finding difficulty Weight loss Behavioral disturbance Anorexia Anxiety Nausea Emotional lability Fatigue Renal calculi Somnolence Uncommon Common
42. New onset epilepsy Bill PA et al. Epilepsy Res 1997; 27: 195-204 53.8% 56.6% Seizure control Study 1: Partial epilepsy= 184 pts, Primary GTCS= 104 pts Outcome measured: Seizure control during a 48 wk maintenance period. Similar in both groups Discontinuation rate VPA (600-2700) OXC (600-2400) Dose (mg/dl) Christe W et al. Epilepsy Res 1997; 26: 451-60 Study 2: Partial epilepsy= 154 pts, Primary GTCS= 95 pts Higher in PHT group Discontinuation rate 58% 59.3% Seizure control 144 143 No of patients PHT (100-560) OXC (600-2100) Dose (mg/dl)
43. New onset epilepsy 60% 61% Seizure control 26% 14% Discontinuation rate Dam M et al. Epilepsy Res 1989; 3: 70-76. 14.5% 2% Discontinuation rate Study 3: 190 patients with GTCS (primary or secondary) Outcome measured: Seizure control during a 48 wk maintenance period. PHT (100-400) OXC (100-1350) Dose (mg/dl) Guerreiro MM et al. Epilepsy Res; 1997; 27: 205-13 Children aged 5-18 yr with partial epilepsy= 151 pts, primary GTCS= 31 pts Study 4 60% 52% Seizure control CBZ (300-1400) OXC (300-1800) Dose (mg/dl)
45. Refractory partial epilepsy: Monotherapy Beydoun A et al. Neurology 2000; 54: 2245-51 Schachter SC et al. Neurology 1999; 52: 732-7 2% 21.6% Hyponatremia Sachdeo R et al. Neurology 2001; 57: 864-71 68 days 28 days Median time to exit OXC (2400 mg/d) OXC (300 mg/d) Study 3 12% 0 100% seizure free 41.2% 93.3% % exiting study OXC (2400 mg/d) OXC (300 mg/d) Study 2 84% 47% % exiting study Placebo OXC Study 1: 10 d trial
46. Children: Refractory partial epilepsy Elterman RD et al. Neurology 1999; 52: 1338-44 Arcas J et al. Epilepsia 2001; 42: 1363-5 3% 10 Discontinuation rate Nausea Headache Vomiting Somnolence 267 children between 3-17 yrs of age. Dizziness Most common adverse effects 5% 4 Rash 8.9% 35% Median reduction in seizures 22% 41% 50% responder rate Placebo OXC (30-46) Dose (mg/kg/d)
52. Children: Refractory partial epilepsy Appleton R et al. Epilepsia 1999; 40: 1147-54 Weight gain Fever Fatigue Viral infection 247 children between 3-12 yrs of age, 12 week trial. Hostility Most common adverse effects 2% 5% Discontinuation rate 13% 28% 2. Secondary GTCS 12% 35% 1. CPS Median reduction in seizures Placebo GBP (23-35 mg/kg/d)
53.
54. Adverse effects No significant drug interactions. Less adverse effects with slow titration of dose. Weight gain Choreoathetosis Fatigue Myoclonus Dizziness Sphincter incontinence Somnolence
60. Refractory partial epilepsy- adjunctive therapy Schmidt D et al. Epilepsy Res 1993; 15: 67-73 Faught E et al. Neurology 2001; 57: 1774-9 Serum ZNS levels did not differ between responders and non-responders. 10% 10% 10% 10% Discontinuation rate 9% 43% 25% 25% 50% responder rate Placebo 400 200 100 Dose (mg/d) Study 2 9.4% 30% 50% responder rate Placebo 20 mg/kg Dose Study 1
61. Schmidt D et al. Epilepsy Res 1993; 15: 67-73 Faught E et al. Neurology 2001; 57: 1774-9 Summary: Effective as add-on therapy in refractory partial epilepsy AAN and AES practice parameters 2004. Adverse effects Depression Abnormal thinking Paranoia Anorexia Rash Somnolence Rhinitis Dizziness Renal calculi Fatigue Uncommon Common
70. AAN and AES practice parameters 2004. No No Zonisamide # Not FDA approved for this indication No No Levetiracetam No Yes (A) Oxcarbazepine No No Tiagabine No Yes # (A) Topiramate Yes # (B) Yes # (A) Lamotrigine No Yes # (A) Gabapentin Absence seizures Partial/mixed seizures Drug AAN Guidelines: Level A or B recommendation for new onset epilepsy (adults and children)
73. AAN level A or B recommendations for refractory primary generalized epilepsy AAN and AES practice parameters 2004. No (U) Zonisamide No (U) Levetiracetam No (U) Oxcarbazepine No (U) Tiagabine Yes (A) Topiramate (only GTCS) No (U) Lamotrigine No (U) Gabapentin Adults and children
74. AAN level A or B recommendations for refractory partial epilepsy: Adults AAN and AES practice parameters 2004. # Not FDA approved for this indication No (U) Yes (A) Zonisamide No (U) Yes (A) Levetiracetam Yes (A) Yes (A) Oxcarbazepine No (U) Yes (A) Tiagabine Yes# (A) Yes (A) Topiramate Yes (B) Yes (A) Lamotrigine No (U) Yes (A) Gabapentin Monotherapy Adjunctive
75. AAN level A or B recommendations for adjunctive therapy in refractory epilepsy: Children AAN and AES practice parameters 2004. Symtomatic epilepsy group largely comprises of LGS pts No (U) No (U) Zonisamide No (U) No (U) Levetiracetam No (U) Yes (A) Oxcarbazepine No (U) No (U) Tiagabine Yes (A) Yes (A) Topiramate Yes (A) Yes (A) Lamotrigine No (U) Yes (A) Gabapentin Symptomatic generalized Partial
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83. Busy days ahead: More AEDs Bialer M et al. Epilepsy Res 2009; 83: 1-43 8. Lacosamide 15. Propylisopropyl acetamide 7. JZP-4 14. YKP 3089 6. Huperzine A 13. Valrocemide 5. Ganaxolone 12. Tonabersat 4. Eslicarbazepine acetate 11. T2000 3. 2-Deoxy-2 glucose 10. Retigabine 2. Carisbamate 9. NAX-5055 1. Brivaracetam