Lowinger D, Benjamin B, Gadd L. [St Luke’s Hospital, Sydney, Australia]
Recurrent Laryngeal Nerve Injury Caused by a Laryngeal Mask Airway
Anaesth Intensive Care 27: 202-205, 1999
There are reports of laryngeal nerve damage after the use of laryngeal mask airways [LMA]. A rare case of permanent unilateral vocal cord paralysis that required thyroplasty for voice restoration is reported.
Male, 44, employed as announcer, underwent ligation of varicose veins. After anesthesia was induced, a size 4 LMA was inserted. The cuff was inflated to 20 mL of air but the cuff pressure was not monitored. After uneventful surgery, the LMA was removed. Over the next 24 hours patient experienced dysphonia without pain, which went on to aphonia by day 2. The left vocal cord was seen to be immobile with no other neurological abnormality. At 6 months left cord paralysis was confirmed without arytenoid cartilage dislocation or other glottic disorder. A trial injection of Gelfoam at 9 months restored good voice for a few weeks. At 12 months, thryroplasty was performed with a 4 mm hydoxyapatite prosthesis, and the patient’s voice improved though the cord paralysis persisted.
Whereas LMA is generally safe and effective, in rare cases it can lead to persistent dysphonia, probably as a result of extensive ischemia with demyelination and neural loss.
Michael L, Rosenberg, MD, and Martin Gizzi, MD, PhD From the New Jersey Neuroscience Institute, Edison, New Jersy,
Otolaryngologic Clinics of North America, Volume 33, No.3 June 2000, Pg. 471- 482
A complete description of the patients symptoms is crucial for the diagnosis.
Definition of Terms : Vertigo, Visual Disorientation, Lightheadedness, and Imbalance
1. Vertigo is the illusory sensation of motion.True vertigo is caused by pathology in the peripheral end organ, the vestibular nerve, the vestibular nuclei, the cerebellum, and the pathways that connect them in the brainstem and, rarely, the cortex.
2. Visual disorientation may mimic acute ataxia. A second, but related, from of visual disorientation is the disruption of depth perception associated with new onset strabismus.
3. Lightheadedness term should be reserved for symptoms similar to those preceding syncope. Lightheadedness is presumably caused by cerebral hypoxia, and may be cardiac or vasovagal in origin.
4. Imbalance, is the inability to maintain the center of gravity and affected patients note unsteadiness, stumbling, and falling.
Vertigo brought on by lying supine and turning to one side is typical of benign paroxysmal positional vertigo [BPPV] . Lightheadedness brought on by getting up quickly from a lying or sitting position.
Patients with BPPV also may have brief vertigo and nystagmus on sitting up quickly.
Patients with cerebellar disease may remain symptomatic as long as they remain in that position.
Patients with motor balance disorders, related to cerebellar degeneration or to parkinsonism, usually report symptoms only when walking.
DURATION OF SYMPTOMS
Vertigo lasting only a few seconds is most likely related to a fixed vestibular lesion, such as follows vestibular neuronitis or the late stages of Menieres disease.
Symptoms lasting from 5 to 90 seconds are typical of BPPV, but most last less than 15 seconds.
Attacks of vertigo lasting 2 to 20 minutes are consistent with a transient ischemic attack [TIA] affecting the posterior circulation.
Characteristically, posterior circulation TIAs are accompanied by diplopia, visual field defects, ataxia, hemisensory loss, or hemiparesis.
The major attacks of Menieres disease last 20 minutes to 24 hours, but most commonly last 4 to 8 hours.
Migraine may present as vertigo lasting minutes or hours.
Acoustic neuroma is an uncommon cause of vertigo as it is a chronic condition and damage to vestibular fibers is compensated for quickly.
An isolated attack of vertigo lasting more than 24 hours is strongly suggestive of vestibular neuronitis.
Vertigo usually lasts 2 to 3 days but occasionally up to a week.
Vertigo lasting more than 3 days is often seen in acute central nervous system disease.
A continuous sensation of vertigo lasting longer than 1 or 2 weeks without daily variation is probably a psychogenic phenomenon.
Vertigo of vestibular origin probably cannot persist on a physiologic basis for more than 2 weeks.
Associated Otologic Complaints
Otologic complaints, such as hearing loss, tinnitus, or ear fullness, provide important clues as to the location of a lesion.
Episodic tinnitus with fluctuating hearing loss may make the diagnosis of Menieres disease.
Classically, patients with Menieres disease experience increased tinnitus and worsening of hearing loss during the time of vertigo attack.
Pain associated with vestibular symptoms should raise suspicion of middle ear disease; however, it also may be associated with invasive disease of the temporal bone and with meningeal irritation.
All sensory information [ other than taste and smell] can be used to give information about position and velocity relative to the surround.
Vision, in particular, is used to stabilize the world. It can suppress strongly any nystagmus and the sense of motion generated by the vestibular system.
In the dark the visual system can no longer provide the stabilizing information.
A normal person has no difficulty relying on vestibular information in such situations, but a patient with a vestibular imbalance may report that the world is moving.
Joel A, Goebel, MD, FACS From the Department of Otolaryngology,Washington University School of Medicine, St. Louis, Missouri
Management Options for Acute Versus Chronic Vertigo
Volume 33, No.33, June 2000, Pg. 483-493
Vertigo is one of the most frequent and disturbing sensations that the practicing otolaryngologist is called upon to treat.
Vertigo is defined as a false illusion of motion with a distinct rotational component.
Recurrent attacks of vertigo are addressed as chronic vertigo.
Rotational chair tests explore the VOR and visual-vestibular interaction.
CPD is used in cases of postural instability to document patterns of sensory organization and motor control during various visual and support-surface challenges.
Most medications for acute attacks of vertigo are centrally acting suppressants for nausea and vomiting.
For acute spells, diazepam 2 to 5 mg three times daily works well. Meclizine 25 mg three times daily and promethazine 25 to 50 mg every 8 hours is another useful combination. Tapered steroid regimen is useful in early vestibular neuritis. They are not to be used chronically or for prophylaxis against subsequent attacks.
Candidates for surgical therapy represent a small fraction [< 5%] of all dizzy patients.
Surgical procedures for vertigo can be described by two characteristics – ablative/non-ablative and hearing preserving/hearing destroyed.
Ablative procedures include transmastoid labyrinthectomy and vestibular nerve section.
In many centers, transtympanic gentamicin therapy has dramatically reduced the necessity for surgical ablation.
Non-ablative procedures include endolymphatic sac decompression, endolymphatic sac shunt, and posterior canal occlusion.
Morgenstern LB, Luna-Gonzales H, Huber JC Jr, et al [ Univ of Texas, Houston]
Worst Headache and Subarachnoid Hemorrhage: Prospective, Modern Computed Tomography and Spinal Fluid Analysis
Ann Emerg Med 32: 297-304, 1998
Although lumbar puncture [LP] may be the best assessment for subarachnoid hemorrhage [SAH], this procedure causes discomfort and is time consuming and costly. The ability of modern head CT to exclude SAH was investigated.
Patients reporting the – worst headache of their lives – should undergo noncontrast head CT. If the CT result is negative, patients should undergo LP with spectrophotometric analysis of the CSF. LP should be recommended because of the potentially devastating consequences of undiagnosed SAH.
Its important to remember that the relative sensitivity of LP and CT behave differently over time : CT may become negative after 48 hours and LP may not become positive until after 12 hours.
The overall conclusion of this article is that, even with contemporary or – modern – scanners, and LP is still required in the face of a negative CT, when the patient presents with a history of – worst headache of my life – especially when the headache has an abrupt onset.
Naumann M. Zellner M, Tokya KV, et al (Bayerische Julius -Maximilians Universitat, Wurzburg, Germany)
Treatment of Gustatory Sweating with Botulinum Toxin.
Ann Neurol 42: 973-975, 1997.
Gustatory sweating (Frey’s syndrome) has been treated with scopolamine or aluminum hydrochloride and tympanic nerve destruction.
Intracutaneous injections of botulinum toxin (BTX) type A are more effective. Forty-five patients were treated. 50% patients reported complete relief and 50% showed substantial improvement.
This is safe and effective method. Long-term follow up is needed. G.R. Holt.
O Nyren, JK McLaughlin, L Yin, et al [Karolinska Inst, Stockholm; Internatl Epidemiology Inst, Rockville, Md; Natl Board of Health and Welfare, Stockholm, Sweden; et al]
Breast Implants and Risk of Neurologic Disease : A Population-based Cohort Study in Sweden
Neurology 50: 956-961, 1998
Records of 7,433 patients with breast implants listed in the Swedish hospital discharge register between 1965 and 1993 were examined for a diagnosis of a neurologic disease.
These were compared with results of 3351 women listed in the same register who underwent breast REDUCTION surgery during the same period – this was the control group.
The study concludes that breast implants do NOT increase the risk of neurologic disorders.
Laura Marsh and Ted M Dawson (Morris K Udall Parkinson’s Disease Research Center of Excellence, Johns Hopkins University School of Medicine,USA)
Treatment of Early Parkinson’s Disease
Ropinirole may improve function, while minimising involuntary movements
BMJ, 1 July 2000, p.1-2
Drug treatment of Parkinson’s disease has been unsatisfactory. Most drugs used have potential risk and benefits. Levodopa, which is one of the commonest drugs used relieves symptoms but in the long term produces involuntary movements and neurotoxicity.
A new drug is now available by the name Ropinirole which is as effective as 5Levodopa and has less adverse reaction of producing abnormal involuntary movements.
JP Leonetti, T Origitano, et al (Loyola Univ, Maywood, III)
Intracranial Complications of Temporal Bone Osteoradionecrosis
Am J Otol 18:223-229, 1997
Osteoradionecrosis of the temporal bone may follow radiation to the brain, parotid gland, nasopharynx, or superior cervical area. Life-threatening intracranial complications may follow.
In 4 patients studied, complications observed were multiple brain abscesses, aneurysm of the internal carotid artery; a cholesteatoma of the external auditory canal with extensive destruction of the mastoid bone leading to thrombosis and meningitis of the sigmoid sinus; meningitis with a small epidural abscess over the middle fossa dura; and prolonged infection of the ear canal, middle ear, and mastoid resulting in fatal otitic meningitis. The 3 patients who underwent surgery (mastoid) survived requiring careful and regular follow-up.
HM Dunniway, DB Welling (Ohio State Univ, Columbus)
Intracranial Tumors Mimicking Benign Paroxysmal Positional Vertigo.
Otolaryngol Head Neck Surg, 118:429-436, 1998.
Benign positional vertigo may not always be benign, as indicated in this study where intracranial tumors were identified in five patients who presented as “benign paroxysmal vertigo.”
When patients of “benign paroxysmal vertigo” do not improve after particle repositioning manoeuver, further assessment is needed to rule out intracranial new growths.
RC O’Reilly, SB Kapadia, D.B. Kamerer (Univ of Pittsburgh, Pa)
Primary Extracranial Meningioma of the Temporal Bone.
Otolaryngol Head Neck Surg 118:690-694, 1998.
Though meningiomas typically occur intracranially, they may rarely arise de novo in the temporal bone. Because of the invasive nature of this tumor, surgical resection is difficult, and postoperative surveillance is necessary
Gordon K Wilcock, Sean Lilienfeld, et al.
Efficacy and safety of galantamine in patients with mild to moderate Alzheimer’s disease : multicentre randomised controlled trial.
BMJ, Vol.321, 9 December 2000, p.1445-9
This was a randomised double-blind parallel group placebo controlled trial in 653 patients with mild to moderate Alzheimer’s disease. Patients randomly assigned to galantamine, had their daily dose escalated over 3-4 weeks to maintenance doses of 24-32mg.
Cholinergic deficits are the most prominent neurochemical disturbances in Alzheimer’s disease. Galantamine is a new drug that reversibly and competitively inhibits acetylcholinesterase and enhances the response of nictonic receptors to acetylcholine.
At 6 months, patients who received galantamine had a significantly better outcome on the galantamine item cognitive subscale of Alzheimer’s disease assessment scale than patients in the placebo group.
Galantamine is effective and well tolerated in Alzheimer’s disease. It slowed the decline of functional ability as well as cognition.
Ian Mckeith, Teodoro Del Ser et al (Univ. of Newcastle upon Tyne, UK)
Efficacy of Rivastigmine in Dementia with Lewy Bodies: a Randomised, double-blind, placebo-controlled international study.
The Lancet, Vol.356, Dec.16, 2000, pg.2031-36.
Dementia with Lewy bodies is a common form of dementia in elderly. Symptoms include fluctuating cognitive impairment, attention deficits, visual hallucinations, parkinsonism. Neuroleptic drugs produce severe sensitivity reactions in such patients. Deficits in cholinergic transmission is seen in brains of these patients and drugs enhancing central cholinergic transmission provide a rational therapeutic approach. Rivastigmine, a cholinesterase inhibitor, was tried in 120 patients. Patients taking rivastigmine were significantly less apathetic and anxious, had fewer delusions and hallucinations while on treatment, than controls. After drug discontinuation differences between rivastigmine and placebo tended to disappear. Known adverse effects of cholinesterase inhibitors (nausea, anorexia, vomiting) were seen but were judged to be within acceptable limits.
Commentary : Cholinesterase inhibitors – expanding applications.
The study expands application of cholinesterase inhibitors to a non-Alzheimer disorder. Postmortem studies of dementia with Lewy bodies (DLB) reveal neuritic plaques like those of Alzheimer’s disease but few neurofibrillary tangles. It is not clear whether it is a variant of Alzheimer’s disease or an independent neurological disorder.
US-FDA requires 2 outcomes for approval of an antidementia agent: drugs must be superior to placebo both on a mesure of core neuropsychological deficits and on a global measure. Tacrine, donepezil, rivastigmine and galantamine are cholinesterase inhibitors that meet these criteria and are approved in some world markets.
Twenty percent of patients treated with cholinesterase inhibitors show a treatment outcome superior to that of placebo.
The reduction in neuropsychiatric symptoms and apparent safety of these agents in patients with extra pyramidal symptoms is very relevant to management of DLB. These patients are exceptionally sensitive to conventional neuroleptic medications, experiencing profound worsening of Parkinsonism.
Rivastigmine has pharmacological properties that distinguish it from other cholinesterase inhibitors, so these findings may not apply to other agents in the class. Rivastigmine may produce GI disturbances and weight loss and these side-effects must be monitored.
Raj K Narayan, (Temple School of Medicine, Philadelphia)
Lack of Effect of Hypothermia after Acute Brain Injury
This Week – New Eng J of Med. Feb.22, 2001, p.537
Whether moderate hypothermia improves the outcome in patients with acute traumatic brain injury has been debated. In this study of 392 patients with severe brain injury who were treated either with the induction of hypothermia within six hours after injury or with normothermia, there was no difference in outcome after six months of follow-up.
The notion that hypothermia might reduce the extent of the damage to the neural tissue in patients who have sustained traumatic brain injuries is an attractive one, and it was supported by some studies in humans and animals. The patients in this large study may have had such severe injuries that no treatment, including hypothermia, was likely to be effective. Alternatively, perhaps hypothermia was achieved too late.
Methylphenidate works by increasing dopamine levels.
BMJ, Feb.3, 2001, pg.259
Methylphenidate works in the treatment of attention deficit hyperactivity disorder by increasing dopamine in children’s brains according to a study reported in the Journal of Neuroscience.
It raises the level of dopamine by blocking the activity of dopamine transporters which remove dopamine once it has been released. Dopamine decreases background firing rates and increases the signal to noise ratio in target neurones. As a result, methylphenidate may improve attention and decrease distractability in activities that normally do not hold the attention of children with attention deficit hyperactivity disorder.
The drug increases dopamine levels like many addictive drugs (cocaine, alcohol, amphetamine) but the key difference may be the length of time that the drugs take to reach the brain. A drug must reach brain very quickly to become addictive. Oral methylphenidate takes about an hour to have effect on the brain, which prevents the drug from causing the ‘high’ produced by most drugs that stimulate dopamine. It could become addictive when tablets are crushed and then either snorted or injected which allows the drug to reach the brain more rapidly.
M Jensenius,B Myrvang, H Storvold, et al [Aker Univ, Oslo, Norway; Ulleval Univ. Oslo, Norway; Baerum Hosp, Norway; et al]
Herpes Simplex Virus Type 2 DNA Detected in Cerebrospinal Fluid of 9 Patients with Mollarets Meningitis
Acta Neurol Scand 98 : 209-212, 1998
Nine patients, aged 31 to 56 years, of Mollarets meningitis were studied. This clinical entity is characterized by recurrent self limiting episodes of aseptic meningitis in otherwise healthy persons. HSV-2-DNA virus was detected in the CSF of all 9 patients. The value of recombinant HSV-2 vaccination for selected patients in reducing the number of attacks of recurrent HSV-2 meningitis is not known.
Prior to this study, in 1991, Mollarets meningitis was reported in 3 women with histories or genital herpes. In that report, treatment with acyclovir eliminated the spells suffered by these women. As prophylactic therapy with acyclovir prevents the meningitis, it is postulated that availability of a vaccine for HSV-2 may eliminate Mollarets meningitis completely.
SV Rajkumar, MA Gertz, RA Kyle (Mayo Clinic and Mayo Found, Rochester, Minn)
Prognosis of Patients with Primary Systemic Amyloidosis Who Present With Dominant Neuropathy.
Am J Med 104: 232-237, 1998.
Peripheral nerve involvement, a well-described characteristic of primary systemic amyloidosis, is the initial manifestation of disease in some patients.
Primary systemic amyloidosis is associated with the deposition of fragments of immunoglobulin light chains in a variety of tissues.
The outcome of disease was assessed in 26 patients with sural nerve biopsy-proven amyloid neuropathy and monoclonal proteins in the serum or urine. These 26 patients met all inclusion criteria from a group of 1282 patients diagnosed (with dominant neuropathy) between 01-01-1978 and 31-12-1994.
The commonest neurologic symptoms were paresthesias (81% patients), muscle weakness (65% patients) and numbness (58%).
Diagnosis of primary systemic amyloidosis is often delayed. The median time to diagnosis is longer than survival after diagnosis. About half to two-thirds of patients have symptoms of autonomic involvement. Patients become immobile or bedridden due to progress of neuropathy. Therapy does not improve neuropathy.
Sr MD Devous, RA Thisted, GF Morgan, et al (Univ of Texas, Dallas; Univ of Chicago; Guilford Pharmaceuticals, Baltimore, Md; et al)
SPECT Brain Imaging in Epilepsy: A Meta-analysis
J Nucl Med 39: 285-293, 1998.
Patients failing to respond to medical treatment of partial epileptic seizures originating in the temporal lobe are now treated surgically. Prior to surgery, single photon emission CT (SPECT) is used to assess the patient. Published studies report different sensitivities for SPECT in imaging regional cerebral blood flow on ictal, interictal or postictal scans. This meta analysis (of 624 patients) reviews relevant studies to determine SPECT sensitivities during different stages of seizure.
When SPECT is performed to assist surgery planning for refractory epilepsy, it is important that ictal or postictal images are obtained in conjunction with interictal images. These interictal images are important for comparisons in the evaluation of perfusion changes on the ictal or postictal images.
P Toti, C De Felice, MLD Plameri, et al (Univ of Siena, Italy; Univ of Antwerp, Wilrijk, Belgium)
Inflammatory Pathogenesis of Cortical Polymicrogyria: An Autopsy Study.
Pediatr Res 44: 291-296, 1998.
This is a study of 32 fetuses spontaneously aborted between 15 and 26 weeks’ gestation because of excessive ascending amnionitis.
Abnormalities in cortical morphology of the brain, can be caused by infection in the fetal adnexa (funisitis – polymorphonuclear leukocytes within the wall of umbilical cord vessels), and the subsequent generation of free radicals.
During hypoxia, the brain generates free radicals. This hypoxia along with free radical generation can cause nonspecific indirect cortical injury that could lead to polymicrogyria in fetuses who survive.
M Kimura, H Sejima, H Ozasa et al [ Shimane Med Univ Japan]
Technetium – 99m – HMPAO SPECT in Patients with Hemiconvulsions followed by Todds Paralysis
Pediatr Radiol 28; 92-9, 1998
Single Photon Emission CT [SPECT] is commonly used to image the brain, there are no reports of the SPECT appearance of the brain after postictal transient focal neurologic trauma. This article describes the SPECT appearance in two patients who had prolonged hemiconvulsion with subsequent transient hemiparesis [ Todds paralysis].
SPECT imaging showed that hyperperfusion of the cerebral hemisphere remained many hours after the postictal neurologic deficits resolved, suggesting that the increased cerebral blood flow did not directly impact the hemiparesis.
Prolonged cerebral hyperperfusion was present even though the patients seizure was short.
The findings suggest, that in patients with hemiconvulsions and Todds paralysis, the prolonged cerebral hyperfusion may be the result of impaired vascular autoregulation and its effects on cerebral function.
FG Sheikh, K Pahan, M Khan, et al (Med Univ of South Carolina, Charleston)
Abnormality in Catalase Import Into Peroxisomes Leads to Severe Neurological Disorder.
Proc Natl Acad Sci U S A 95:2961-2966, 1998.
Functional abnormality of peroxisomes leads to progressive neurologic disorders.
Human skin fibroblast cell lines from patients with multiple peroxisomal dysfunctions and normal transport and location of PTS1- and 2-containing proteins (PTS= peroxisomal targeting signal sequence 1 & 2) but with abnormal localization of catalase were studied.
There is a PTS-1 and 2-independent pathway in fibroblasts that is used to transport catalase into human peroxisomes. Impairment of this pathway causes catalase to be improperly localized in the cytosol, instead of being localised in peroxisomes. Without catalase, H2O2 accumulates and suppresses the activities of other peroxisomal proteins, which leads to peroxisomal disease with severe neurologic malfunction.
JM Freeman, EPG Vining, DJ Pillas, et al (Johns Hopkins Med Institutions, Baltimore, Md)
The Efficacy of the Ketogenic Diet – 1998: A Prospective Evaluation of Intervention in 150 children.
Pediatrics 102: 1358-1363, 1998.
The Ketogenic diet (high fat low protein, low CHO diet) first used in the 1920s, is designed for use in children, with difficult-to-control seizures.
The current role of this diet for children with refractory seizures (to modern antiepileptic drugs and surgery) was evaluated in a prospective study of 150 children.
The children were followed for at least one year or until they went off the diet.
The authors conclude that the ketogenic diet appears to reduce seizure frequency for children with refractory seizures.
Klaus Scheidtmann, Wolfgang Fries et al
Effect of Levodopa in Combination with Physiotherapy on Functional Motor Recovery After Stroke: A Prospective, Randomised, Double-blind Study
Lancet, Vol.358, September 8, 2001, Pg. 787-90
Summary : Physiotherapy has been the only way of improving motor function in hemiplegia after stroke. Administration of amphetamine in addition to exercise improves motor recovery in animals, probably by increasing the concentration of norepinephrine in the central nervous system. Aim of the present study was to find out whether levodopa could have similar effect.
The authors conducted a prospective, randomised, placebo-controlled double-blind study in 53 primary stroke patients. For the first 3 weeks patients received single doses of levodopa 100 mg or placebo daily in combination with physiotherapy. For the second 3 weeks patients had only physiotherapy. Motor function was quantitatively assessed every week with Rivermead motor assessment (RMA).
The interpretation of the study was that single dose of levodopa is well tolerated and when given in combination with physiotherapy, enhances motor recovery in patients with hemiplegia. In view of its minimal side-effects, levodopa will be a possible add on during stroke rehabilitation.
What Can Sex Hormones Do For The Damaged Brain?
Lancet, Vol.358, September 8, 2001, Pg. 818
Summary : Donald Stein from Emory University, Atlanta, Georgia has championed the cause of progesterone as a neuroprotective steroid. He is about to start a pilot clinical study on the use of progesterone to halt the cascade of cell death that follows traumatic injury.
A possibility is that one of progesterone’s metabolites (allopregnanolone) is protecting neurones after trauma by preventing excitatory cell death after acute trauma. Oestrogen may also have a similar capability, and part of the beneficial effect of oestrogen in preventing stroke and Alzheimer’s disease may be because of its antioxidant activity. A single phenol group is responsible for the free-radical scavenging and Christian Behl of the Max Planck Institute of Psychiatry, Munich, Germany has attached some bulky methyl groups to stop it from binding to the oestrogen receptor.
The result is 2,4,6-trimethylphenol (TMP), a molecule that no longer triggers a sexual differentiation but retains its powerful anti-oxidant properties. Preliminary results in animal models of stroke are very encouraging.
The TMP is a small molecule that readily passes blood-brain barriers and protects the brain against ischaemia-induced damage.
Oxcarbazepine: Anticonvulsant Profile and Safety
Drugs of Today, May 2001, 37(5): 333-355
Oxcarbazepine is a molecule chemically related to carbamazepine that shares most of the pharmacological and therapeutic effects of carbamazepine while displaying a more favourable profile regarding tolerability and drug-drug interactions. In contrast to carbamazepine, oxcarbazepine is metabolized through cytochrome P450-independent reductase, and is thus devoid of inductive effects on hepatic oxidative metabolism. Oxcarbazepine has been shown to be useful both as monotherapy and adjunctive therapy in patients with partial seizures with or without secondary generalization. The drug has been documented as safe and effective in adults as well as children aged 4-16 years. Additional data suggests that oxcarbazepine might improve cognition and psychomotor performance and might increase alertness, in contrast to the cognition/psychomotor impairment observed with some other antiepileptic drugs. Both the pharmacokinetic advantages over other anticonvulsant drugs and the lack of pharmacological interactions with oxcarbazepine may point to this drug as a first-line treatment for the management of partial and tonic-clonic epilepsy.
C Chiron, M.C. Marchand et al
Stiripentol in severe myoclonic epilepsy in infancy: a randomised placebo-controlled syndrome-dedicated trial
The Lancet, vol.356, Nov.11, 2000, pg.1638
Stiripentol is an inhibitor of cytochrome P450 that showed antiepileptic efficacy in severe myoclonic epilepsy in infancy (SMEI) in association with clobazam and valproate in an open study. To confirm these results, 41 children with SME1 were included in a randomised, placebo controlled, add-on trial.
After a baseline period of 1 month, placebo (n=20) or stiripentol (n=21) was added to valproate and clobazam during a double blind period of 2 months. Patients then received stiripentol in an open fashion. Responders were defined as having more than 50% reduction in the frequency of clonic (or tonic-clonic) seizures during the second month of the double-blind period compared with baseline.
This controlled trial shows the antiepileptic efficacy, of add-on stiripentol in children with SMEI. The results also provide good reason to focus studies on a specific epilepsy syndrome a small sample of patients is sufficient to show the efficacy that might have been missed in a heterogeneous population.
Epilepsy syndrome-specific anti-epileptic drug therapy for children.
Lancet, vol.356, Nov.11, 2000, pg.1623
Several epilepsy syndromes of childhood are characterised by primary generalised seizures that are sometimes exacerbated by anti-epileptic drugs that are effective among adults with partial seizures.
It is very difficult to recruit children into randomised, placebo-controlled clinical trials of anti-epileptic drugs that are on the market, so some potentially important indications for the newer anti-epileptic drugs have not been appropriately tested in children.
C Chiron and colleagues had to recruit patients from 15 centres to get 42 patients for their trial of stiripentol among a homogeneous group of children with severe myoclonic epilepsy in infancy. Patients were assigned stiripentol or placebo as add-on therapy for 2 months. Despite the small number of patients, the trial showed a superiority of stiripentol over placebo.
Stiripentol’s known primary mechanism of action is inhibition of the cytochrome P450 system. Because this action increases concentrations of co-medications such as valproate and clobazam, it is difficult to prove in a trial with an add-on design that the reduction in seizure frequency is due to stiripentol. Although Chiron and colleagues argue that the size of the effect found in this trial is greater than would be expected from the impact of increased concentrations of valproate and clobazam alone, monotherapy trials may be required to convince some clinicians that the ability of stiripentol to reduce seizure frequency is independent of its effect on other anti-epileptic agents.
J. P. Mohr, j. l. p. Thompson, et al
A Comparison of Warfarin and Aspirin for the Prevention of Recurrent Ischemic Stroke
New Eng J Med. Vol.345, Nov. 15, 2001, pg.1444-51
Despite the use of antiplatelet agents, usually aspirin, in patients who have had an ischemic stroke, there is still a substantial rate of recurrence. Therefore, the authors investigated whether warfarin, which is effective and superior to aspirin in the prevention of cardiogenic embolism, would also prove superior in the prevention of recurrent ischemic stroke in patients with a prior noncardioembolic ischemic stroke.
In a multicenter, double-blind, randomized trial, the authors compared the effect of warfarin (at a dose adjusted to produce an international normalized ratio of 1.4 to 2.8) and that of aspirin (325 mg per day) on the combined primary end point of recurrent ischemic stroke or death from any cause within two days.
Over a two-year period, the authors found no difference between aspirin and warfarin in the prevention of recurrent ischemic stroke or death or in the rate of major hemorrhage. Consequently, the authors regard both warfarin and aspirin as reasonable therapeutic alternatives.
Tenebaum A, Motro M, Feinberg MS, et al
Large Plaques in Descending Aorta may Predispose to Stroke and Peripheral Embolism
Chest 118: 1703-1708, 2000
The authors found large mobile plaques in the descending thoracic aorta by trans-esophageal echocardiography in patients with cerebral and peripheral emboli. They suggest that these plaques may be a real source for emboli and not just a marker of severe atherosclerosis.