Paul Reading Maurice Curtis, Andrew Naylor, Richard Faull ... - ACNR

Neurophysiology ArticlePrescribing information: AVONEX ®Presentations: Lyophilised powder for injection for IM administration containinga 30µg dose (6 million IU) of Interferon beta-1a per vial. Solution for injection ina pre-fi lled syringe of 0.5ml for IM administration containing 30µg dose (6 millionIU) of Interferon beta-1a. Indications: For the treatment of ambulatory patientswith relapsing multiple sclerosis characterised by at least 2 recurrent attacks ofneurologic dysfunction (relapses) over the preceding 3-year period without evidenceof continuous progression between relapses. AVONEX ® slows the progression ofdisability and decreases the frequency of relapses. AVONEX ® is also indicated forthe treatment of patients who have experienced a single demyelinating event withan active infl ammatory process if it is severe enough to warrant treatment withintravenous corticosteroids, if alternative diagnoses have been excluded, and if theyare determined to be at high risk of developing clinically defi nite multiple sclerosis(see SPC for further information). Treatment should be discontinued in patients whodevelop chronic progressive multiple sclerosis. Dosage and Administration: Therecommended dosage of AVONEX ® in the treatment of relapsing MS is 30µg injectedIM once a week. AVONEX ® lyophilised powder presentation should be reconstitutedwith the solvent supplied. Treatment should be initiated under supervision of aphysician experienced in the treatment of the disease. An antipyretic analgesic isadvised to decrease the fl u-like symptoms associated with AVONEX ® administration.AVONEX ® should not be used in children. Contraindications: Initiation of treatmentin pregnancy. Patients with a history of hypersensitivity to natural or recombinantinterferon beta or any of the excipients. Patients with current severe depressiondisorders and/or suicidal ideation. Precautions: CNS: AVONEX ® should be used withcaution in patients with previous or current depressive disorders, in particular to thosewith antecedents of suicidal ideation. Depression and suicidal ideation are known tooccur in increased frequency in the multiple sclerosis population in association withinterferon use. Patients treated with AVONEX ® should be advised to immediately reportany symptoms of depression and/or suicidal ideation to their prescribing physician.AVONEX ® should be administered with caution to patients with a history of seizures,to those receiving treatment with anti-epileptics, particularly if their epilepsy is notadequately controlled with anti-epileptics. Pregnancy and lactation: Initiation oftreatment is contraindicated during pregnancy. Women of child bearing potentialshould take appropriate contraceptive measures. If the patient becomes pregnant orplans to become pregnant while taking Avonex, discontinuation of therapy should beconsidered. General: AVONEX ® should be used with caution in patients with cardiacdisease, severe renal or hepatic failure or severe myelosuppression, and these patientsshould be closely monitored. Routine periodic blood chemistry and haematologytests are recommended during treatment with AVONEX ® . Laboratory abnormalitiesmay also occur which do not usually require treatment. Drug interactions: No formalinteraction studies have been conducted with AVONEX ® in humans. Clinical studiesindicate that corticosteroids or ACTH can be given during relapses. Caution should beexercised in combining AVONEX ® with medicinal products with a narrow therapeuticindex and dependent on hepatic cytochrome P450 for clearance. Side Effects: Themost commonly reported symptoms are of the fl u-like syndrome: muscle ache, fever,chills, asthenia, headache and nausea. Other less common events include: Bodyas a whole: Anorexia, hypersensitivity reactions, weight loss, weight gain, severeallergic reactions (anaphylactic reactions or anaphylactic shock), syncope. Skin andappendages: Alopecia, angioneurotic oedema, injection site reaction including pain,pruritus, rash, urticaria. Digestive system: Diarrhoea, hepatitis, liver function testabnormalities, vomiting. Cardiovascular system: Chest pain, palpitations, tachycardia,and vasodilatation and rarely arrhythmia, cardiomyopathy, congestive heart failure.Haematological system: Thrombocytopenia and rare cases of pancytopenia.Reproductive system: Metrorrhagia and/or menorrhagia. Nervous system: Anxiety,dizziness, insomnia, paraesthesia, seizures, depression, suicide (see Precautions).Transient neurological symptoms that mimic MS exacerbations may occur followinginjections. Musculoskeletal system: Arthralgia, pain, transient hypertonia and/or severe muscular weakness. Respiratory system: Dyspnoea. Autoimmunedisorders, central nervous system disorders and laboratory abnormalities havebeen reported with interferons. Rare cases of arthritis, hypo- and hyperthyroidism,lupus erythematosus syndrome, confusion, emotional lability, psychosis, migraineand very rare cases of autoimmune hepatitis have been reported with AVONEX ® . Forfurther information regarding adverse events please refer to the Summary of ProductCharacteristics. Preclinical Safety: Fertility and developmental studies with a relatedform of Interferon beta-1a in Rhesus monkeys show anovulatory and abortifacienteffects at high doses. No teratogenic effects or effects on foetal development wereobserved. Legal Classifi cation: POM. Pack Size and UK NHS Price: Box containingfour injections £654. Reimbursed through High Tech Scheme in Ireland. PackageQuantities: Lyophilised Powder: 1 box containing four trays. Each tray contains a3ml glass vial with BIO-SET device containing a 30µg dose of Interferon beta-1a pervial, a 1ml pre-fi lled glass syringe of solvent and one needle. Pre-fi lled Syringe: 1box containing four trays. Each tray contains a 1ml pre-fi lled syringe made of glasscontaining 0.5ml of solution (30µg dose of Interferon beta-1a) and one needle.Product Licence Numbers: EU/1/97/033/002-003. Product Licence Holder: BiogenIdec Ltd., 5 Roxborough Way, Foundation Park, Maidenhead, Berkshire SL6 3UD,United Kingdom. Date of last revision of Prescribing Information: September 2006.Please refer to the Summary of Product Characteristics for further information.For UK only:Information about adverse event reporting can be found at www.yellowcard.gov.uk.Adverse events should also be reported to Biogen Idec Ltd., on 08000 286639.References:1. Halper J et al. J Neurosci Nurs 2003; 35: 70-81.2. Rudick RA et al. Poster presented at ECTRIMS. October 2007; Prague.Date of preparation: January 2008AVOO-PAN-22918Table 3: Relation between seizure outcome and removal of abnormalSPES areas.Favourable Poor TotalOutcome (I-II) Outcome (III-IV)Completely removed (CR) 21 1 22Partially removed (PR) 5 2 7Not removed (NR) 0 3 3No late responsesobserved (NL) 5* 3 8Total 31 9 40*4 patients showed continuous interictal spikes (cis) suggestive of corticaldysplasia at the areas of seizure onset, which made assessment of thepresence of delayed responses at these regions impossible (probably falsenegatives of SPES).those of spontaneous epileptiform discharges. Thirdly, at present SPEScan only be carried out in patients assessed with intracranial electrodes,and shares with such recordings their limitations with regard to spatialsampling. The combined use of transcranial magnetic stimulation(TMS) and simultaneous EEG could help to study cortical excitability infocal epilepsy. 11ConclusionSingle pulse electrical stimulation is a safe and reliable technique for identifyingepileptogenic cortex, as evidenced by the close relationship betweenthe topography of abnormal responses and location of electrographicseizure onset, surgical outcome, and pathological abnormalities. Our findingssuggest that surgery should remove abnormal SPES areas. This is ofparamount clinical relevance since SPES appears to provide additional evidenceof epileptogenicity during the interictal period, and it appears to bea good predictor of pathology and surgical outcome.At the very least, SPES provides additional evidence that can be used toreduce the need to capture seizures, allowing invasive EEG telemetry tobe performed for shorter periods. It may in some instances even replaceictal recording as a method of locating the epileptogenic zone, allowingintraoperative identification of epileptogenic cortex immediately beforeresection. Furthermore, the technique may also prove of value duringelectrode implantation to determine whether the sites chosen are likely tolie within the epileptogenic zone.References1. Hauser WA, Annegers JF, Kurland LT. Incidence of epilepsy and unprovoked seizures inRochester, Minnesota: 1935-1984. Epilepsia 1993;34(3):453-68.2. Brodie MJ, Shorvon SD, Canger R, Halasz P, Johannessen S, Thompson P et al. Commissionon European Affairs: appropriate standards of epilepsy care across Europe. ILEA. Epilepsia1997;38(11):1245-50.3. Alarcón G, Valentín A, Watt C, et al. Is it worth pursuing surgery for epilepsy in patientswith normal neuroimaging? J Neurol Neurosurg Psychiatry 2006 Apr;77(4):474-80.4. Valentín A, Anderson M, Alarcón G, et al. Responses to single pulse electrical stimulationidentify epileptogenesis in the human brain in vivo. Brain 2002;125(Pt 8):1709-18.5. Valentín A, Alarcón G, Garcia-Seoane JJ, et al. Single-pulse electrical stimulation identifiesepileptogenic frontal cortex in the human brain. Neurology 2005;65(3):426-35.6. Valentín A, Alarcón G, Honavar M, et al. Single pulse electrical stimulation for identificationof structural abnormalities and prediction of seizure outcome after epilepsy surgery: a prospectivestudy. Lancet Neurol 2005;4(11):718-26.7. Flanagan D, Valentín A, Alarcón G, Boyd SG. Single pulse electrical stimulation of the cortexduring prolonged subdural EEG monitoring in children. Abstract for presentation at 21stAnnual Scientific Meeting of the Epilepsy Society of Australia 2006.8. Wilson CL, Isokawa M, Babb TL, Crandall PH. Functional connections in the human temporallobe. I. Analysis of limbic system pathways using neuronal responses evoked by electricalstimulation. Exp Brain Res 1990;82:279-92.9. Wilson CL, Isokawa M, Babb TL, Crandall PH, Levesque MF, Engel J, Jr. Functional connectionsin the human temporal lobe. II. Evidence for a loss of functional linkage between contralaterallimbic structures. Exp Brain Res 1991;85:174-87.10. Lacruz ME, García Seoane JJ, Valentín A, Selway R, Alarcón G. Frontal and temporal functionalconnections of the living human brain. Eur J Neurosci. 2007 Sep;26(5):1357-70.11. Valentín A, Arunachalam R, Mesquita-Rodrigues A, et al. Late EEG responses triggered bytranscranial magnetic stimulation (TMS) in the evaluation of focal epilepsy. Epilepsia. 2007Nov 19 [Epub ahead of print].18 I ACNR • VOLUME 8 NUMBER 1 • MARCH/APRIL 2008