Y P O C T O N An Introduction to Seizures O for the TMS - PowerPoint PPT Presentation

Y P O C T O N An Introduction to Seizures O for the TMS Clinician or Investigator D E S Bernard S. Chang, M.D., M.M.Sc. Associate Professor of Neurology A Harvard Medical School E Comprehensive Epilepsy Center Beth Israel Deaconess Medical Center L P

Y P A 30-year-old woman with O an episode of left facial twitching C T O N O D E S A E L P

Y P O Outline C  Definitions and epidemiology T O  Seizures as an adverse effect of TMS N O  Epilepsy as a therapeutic target of TMS D  Differential diagnosis and seizure types E S  The acute response to an unexpected seizure A E  Diagnostic workup and management L P

Y P Seizures are defined by pathophysiology, O not by specific symptoms C T • Seizure O – A clinical episode of neurologic dysfunction caused by the N abnormal hypersynchronous activity of a group of O neurons D • Epilepsy E S – Any disorder characterized by a tendency toward A recurrent, unprovoked seizures E – In practice, diagnosed after two unprovoked seizures L P

Y P Seizures and epilepsy are common, and O incidence is highest in the young and in the old C • Prevalence of epilepsy in the general population is about 0.5%, or 1 in 200 T persons O • Cumulative lifetime incidence of one or more seizures is 5-10%, including febrile seizures N Annegers, 2001 O D E S A E L P Stephen and Brodie, 2000

Y Seizures occur when an imbalance of excitation P O and inhibition exists in the nervous system C T Inhibition O Excitation N O D Examples E hypoxic-ischemic brain injury strokes S developmental brain malformation CNS infections A traumatic brain injury neurodegenerative diseases E neurosurgery CNS demyelination/inflammation L brain tumors inborn errors of metabolism P alcohol-related systemic illness (metabolic, infectious) Modified from White, 2001

Y The early literature highlighted seizures P O as a possible complication of TMS C T O N O D Classen et al., 1995 E 1 stroke patient out of 150 developed a seizure within 30 secs after TMS • S (Homberg and Netz, 1989) A 2 healthy subjects out of 9 developed seizures acutely during TMS E • (stimulation frequency 10 Hz, 25 Hz) (Pascual-Leone et al., 1993) L P

Y P Data now suggest that TMS-associated seizures O are rare in those without prior history C T It is unclear if single- or paired-pulse TMS have ever been associated with a • seizure in a normal individual without risk factors (Kratz et al., 2011; Alonso-Alonso O et al., 2011) N As of a comprehensive 2008 review, there had been 16 total cases of • O seizures in individuals without an apparent prior history of seizures, 9 of which occurred since the 1998 safety guidelines, and most of which D involved rTMS and some possible pro-epileptogenic risk factors (Rossi et al., 2009) E S One seizure was reported in a healthy individual without risk factors • receiving continuous theta burst stimulation (Obermann and Pascual-Leone, 2009) A E L P

Y The risk of TMS-associated seizures even in P O those with known epilepsy is still quite low C T O N O D E S Schrader et al., 2004 A E • All were typical seizures followed by typical recovery L • Impossible to be certain about their relationship to TMS P • No long-lasting adverse effects

Y P The risk is low even in patients with O known epilepsy undergoing rTMS C T Crude risk of induced seizures in patients with known epilepsy • O during a rTMS session estimated to be 1.4% (4 out of 280 patients) N Only one reported case of an atypical seizure, apparently arising • from stimulation site (16 Hz) O D No instances of status epilepticus • Bae et al., 2007 E S No TMS-linked seizures in 152 patients with epilepsy who had • A weekly rTMS at ≤1 Hz in therapeutic trials E L tabulated in Rossi et al., 2009 P

Y In an epilepsy patient, it may be hard to know P O whether a seizure during TMS is causally related C T O N O D E S A E L • Clinical seizure in a 22-year-old man with drug-resistant P epilepsy of frontopolar onset Vernet et al., 2012

Y P But seizures are still important O to learn about as part of TMS training C • They are the most dramatic and medically dangerous acute T complication of TMS O N • IRB/ethics boards expect them to be addressed as a risk of TMS research O D • The world of TMS usage has expanded: E – To researchers who are not physicians or clinicians who are not familiar with neurological disorders S A – To labs that are not located proximate to medical facilities E – To patient or subject populations with known epilepsy or with neurological disorders that lead to an increased risk of seizures L P

Y P O Outline C  Definitions and epidemiology T O  Seizures as an adverse effect of TMS N O  Epilepsy as a therapeutic target of TMS D  Differential diagnosis and seizure types E S  The acute response to an unexpected seizure A E  Diagnostic workup and management L P

Y P In selected epilepsy patients, low-frequency O rTMS to cortical targets reduces seizures C T O N O D E S A Targeting the epileptogenic zone in 64 Targeting cortical malformations in patients, 0.5 Hz rTMS high-intensity 21 patients, 1 Hz rTMS vs. sham for E 5 sessions vs. low-intensity for 2 weeks L P Sun et al., 2012; Fregni et al., 2006

Y TMS-evoked potentials recorded on EEG may be P O a useful and sensitive biomarker of epilepsy C T This patient had no O interictal epileptiform N discharges (spikes) on 11 days of O continuous EEG D recording E S A E L P Shafi et al., 2015

Y P We are using MRI connectivity to guide rTMS O targeting in epilepsy patients with deep lesions C T O N O D E S A E L P Shafi et al., 2015

Y P Seizures are classified by their origin in the O brain and associated clinical features C T • Partial-onset or focal-onset O – Simple partial N – Complex partial O • Generalized-onset D – Generalized tonic-clonic – Absence E – Myoclonic S • All partial-onset seizures can become secondarily generalized A E L P

Y P O C T O N O D E S A E L P Netter F, Ciba collection of medical illustrations

Y P O C T O N O D E S A E L P Netter F, Ciba collection of medical illustrations

Y P O C T O N O D E S A E L P Netter F, Ciba collection of medical illustrations

Y P Most seizures in adults are focal-onset, even O those that end up generalized tonic-clonic C T O N O D E S A E L P Seizure types in the Holt-Seitz et al., 1999 elderly population

Y P Complex partial seizures of temporal lobe origin O can have fairly distinct characteristics C T O N O D E S A E L P

Y P Some focal seizures may have minimal motor O manifestations and be misdiagnosed, however C T O N O D E S A E L P

Y P All focal-onset seizures can become O secondarily generalized tonic-clonic seizures C T O N O D E S A E L P

Y P The generalized tonic-clonic phase has a O fairly stereotyped appearance C T O N O D E S A E L P

Y P O Outline C  Definitions and epidemiology T O  Seizures as an adverse effect of TMS N O  Epilepsy as a therapeutic target of TMS D  Differential diagnosis and seizure types E S  The acute response to an unexpected seizure A E  Diagnostic workup and management L P

Y P There is little to do acutely O for most types of seizures C T • Absence, myoclonic, simple partial seizures O – Usually no intervention necessary except reassurance when N event ends O D • Complex partial seizures E – Allow event to run its course while preventing patient from S encountering harm A – Patients may become hostile or violent if actively restrained E L P

Y P Some standard measures are taken for O generalized tonic-clonic seizures C T O N Cushion Head Loosen Necktie O D Turn On Side Nothing In Mouth E S A Look For ID Don't Hold Down E L P Epilepsy As Seizure Ends ...Offer Help Foundation

Y P Life-threatening complications O of isolated seizures are rare C T • Vast majority of generalized tonic-clonic seizures last O less than 120 seconds N O • Vomiting, aspiration, face-down positioning D E • Cardiac arrest or prolonged respiratory arrest S A E L P

Y P What are the initial elements in O evaluating a possible seizure? C • History T – Details of the event O – Past history of seizure-like symptoms or similar events N – History of head trauma, febrile seizures, CNS infection – Family history of seizures O • Exam D – General exam: evidence of head injury, meningismus, tongue bite E – Neurologic exam: evidence suggesting a focal brain lesion • Labs S – Evidence of infection or metabolic disturbance: CBC, electrolytes, A toxicologic screen, drug levels E L P

Y P Many unexpected events, including other TMS O adverse effects, can appear similar to seizures C T • Seizure O • TIA N • Confusion/delirium • Syncope O • Medication side effects D • Cardiac arrhythmia • Migraine (without headache) E • Hallucinations from sensory deprivation S • Myoclonus A • Transient global amnesia E • Vertigo L P