Edward Reynolds

Vitamin B12, folic acid, and the nervous system

There are many reasons for reviewing the neurology of vitamin-B12 and folic-acid deficiencies together, including the intimate relation between the metabolism of the two vitamins, their morphologically indistinguishable megaloblastic anaemias, and their overlapping neuropsychiatric syndromes and neuropathology, including their related inborn errors of metabolism. Folates and vitamin B12 have fundamental roles in CNS function at all ages, especially the methionine-synthase mediated conversion of homocysteine to methionine, which is essential for nucleotide synthesis and genomic and non-genomic methylation. Folic acid and vitamin B12 may have roles in the prevention of disorders of CNS development, mood disorders, and dementias, including Alzheimers disease and vascular dementia in elderly people.

The Prognosis for Seizure Control in Newly Diagnosed Epilepsy

We assessed the prognosis for seizure control in 106 patients who were referred to an adult neurology clinic with previously untreated tonic-clonic, partial, or mixed seizures and were followed prospectively for a median of 66 months (range, 6 to 96). Twenty-six patients remained completely free of seizures for as long as they were followed. Actuarial analysis showed that 35 per cent of patients could be expected to enter a seizure-free period of at least two years at the start of treatment, 73 per cent would have had a two-year seizure-free period at the end of four years, and 82 per cent would have had a two-year seizure-free period at the end of eight years. Of 79 patients whose seizures were completely controlled for at least two years, 51 subsequently remained seizure-free. If seizures continued for up to two years after the start of treatment, the probability of subsequent seizure control fell by half. The presence of partial seizures; a high frequency of tonic-clonic seizures before treatment; a neurologic, social, or psychiatric handicap; and a family history of epilepsy each indicated a worse prognosis. We conclude that the long-term pattern of seizure control is largely established during the first two years of treatment.

The Clinical Potential of Ademetionine (S-Adenosylmethionine) in Neurological Disorders

SummaryThis review focuses on the biochemical and clinical aspects of methylation in neuropsychiatrie disorders and the clinical potential of their treatment with ademetionine (S-adenosylmethionine; SAMe). SAMe is required in numerous transmethylation reactions involving nucleic acids, proteins, phospholipids, amines and other neurotransmitters. The synthesis of SAMe is intimately linked with folate and vitamin B12 (cyanocobalamin) metabolism, and deficiencies of both these vitamins have been found to reduce CNS SAMe concentrations. Both folate and vitamin B12 deficiency may cause similar neurological and psychiatric disturbances including depression, dementia, myelopathy and peripheral neuropathy. SAMe has a variety of pharmacological effects in the CNS, especially on monoamine neurotransmitter metabolism and receptor systems. SAMe has antidepressant properties, and preliminary studies indicate that it may improve cognitive function in patients with dementia. Treatment with methyl donors (betaine, methionine and SAMe) is associated with remyelination in patients with inborn errors of folate and C-l (one-carbon) metabolism. These studies support a current theory that impaired methylation may occur by different mechanisms in several neurological and psychiatric disorders.

Predictive value of interictal epileptiform discharges during non-REM sleep on scalp EEG recordings for the lateralization of epileptogenesis

Summary: Purpose: EEG recording during sleep is widely used in the assessment of epilepsy, particularly in candidates for surgery, yet the diagnostic value of this procedure is not well established. We evaluated the predictive reliability of interictal epileptiform discharges (IEDs) for localization in pre‐surgical patients with temporal lobe epilepsy (TLE) during non‐REM sleep.

The ILAE/IBE/WHO Global Campaign against Epilepsy: Bringing Epilepsy “Out of the Shadows”

Epilepsy affects at least 100 million people worldwide at some time in their lives, especially in childhood and adolescence. It is a universal problem involving all ages, races, social classes, and nations. Nevertheless, it has been misunderstood, feared, and stigmatized for more than 3000 years. The psychosocial and economic consequences of epilepsy are considerable in developed nations but are even greater in developing nations, where the treatment gap may vary from 60 to 98%. To address the long-standing worldwide neglect of this disease, a campaign titled Epilepsy: Out of the Shadows has been launched by an alliance of three global organizations: the International League against Epilepsy (ILAE), the International Bureau for Epilepsy (IBE), and the World Health Organization (WHO). Global, regional, and national initiatives are currently underway.

A bridge between neurology and psychiatry

Sir Denis Hill, R.H.Cawley Sir Denis Hill at the Middlesex, A.H.Crisp the bridge between neurology and psychiatry, Denis Hill neurologists and psychiatrists, W.A.Lishman structure and function in neurology and psychiatry, E.H.Reynolds on states of consciousness, Denis hill sleep and its disturbances, A.H.Crisp disorders of verbal expression in neuropsychiatry, D.F.Benson body image disturbances in neuropsychiatry, D.J.Cutting neuropsychology - memory and hippocampal pathology, J.Oxbury and S.Oxbury movement disorders in neuropsychiatry, C.D.Marsden hysteria, M.R.Trimble anxiety and phobic states, M.Roth a psychobiological view of depression, A.H.Crisp the brain in schizophrenia, M.A.Reveley epilepsy and mental illness, E.H.Reynolds the significance of a seizure, P.Fenwick dyscontrol, P.Fenwick laterality in neuropsychiatry, B.K.Toone the EEG in neuropsychiatry, G.W.Fenton neuropsychopharmacology, M.R.Trimble neuropsychiatric disorders and the new genetics, S.A.Whatley et al neurotransmitters in neuropsychiatry, M.Rossor.

The influence of carbamazepine and phenytoin on memory and other aspects of cognitive function in new referrals with epilepsy

Several diffcrcnt biological and psychosocial factors may contribute to impairment of cognitivc function, mood and bchaviour in epileptic subjects [ I , 21. Thc factors which may spccifically influence memory function in cpilcptic childrcn and adults havc bccn discussed at thc two prcvious workshops in this series [3-51 and have also been reviewed by Brown & Reynolds [6]. ‘They include underlying structural brain lesions [7]; temporal lobc pathology or dysfunction [8-lo]; the age of onset and/or thc duration of cpilcpsy [7]; the influencc of “subclinical” abnormal electrical activity [ 1 1 , 121 and anticonvulsant drug therapy [3, 131. In this paper we present and discuss furthcr obscrvations on the effect of anticonvulsants on cognitive function, with particular reference to memory. Until recently it has bccn traditional to treat epileptic patients with multiple drugs (polytherapy). Howcvcr, there is now cvidence that most new referrals with cpilepsy can be controlled with single drug therapy [14]. Moreover, monothcrapy has considerable advantagcs ovcr polythcrapy for the mental function of epileptic subjects [15]. Two of thc most widely used anticonvulsants are phenytoin (DPH) and carbamazepine (CBZ). As the anticonvulsant efficacy of these two drugs is similar [ 16, 171, the decision as to which drug to use may be influenced by potential side effects, especially on mental function. Thcrc is some evidence that carbamazepinc may have fewer adverse efkcts on mental function than other anticonvulsants [15, 16, 181. These previous studies havc been undertaken in normal voluntccrs [ 181 or chronic cpilcptic patients [ 161. We hcrc present the results of a study of ncw rcfcrrals waith epilepsy who havc reccntly bccn started on treatment with cithcr phenytoin or carbamazcpinc, with blood lcvcl m o n toring of the drug, and relatively good control ofscizures. They have ncvcr prc~~iously received other anticonvulsant drugs. I n choosing the tasks for this study, attention was paid to thr likely scnsitivity to drug effects according to thc past literaturc. I n addition, tests were chosen for thcir ability to isolate particular cognitive functions according to theoretical research. Some effort was also made to relatc thc laboratory findings for the patients to thcir pcrformancc in evcryday life through the us” of two memory questionnaires.

Introduction: Epilepsy in the World

The launch of the Second Phase of the International League Against Epilepsy (ILAE)/International Bureau for Epilepsy (IBE)/World Health Organisation (WHO) Global Campaign Against Epilepsy in Geneva on February 12, 2001, was a milestone in the history of epilepsy and indeed of the League and the Bureau. It reflected the recognition of epilepsy as a global health problem and challenge of high priority and the elevation of the campaign to the highest WHO level, the first neurologic disorder to be accorded this status. During the 1990s, the ILAE and IBE grew rapidly into truly global organisations, and they established an excellent working relationship. As President of ILAE, I realised in 1995 that the stage was now set for a joint initiative by the League (professional), the Bureau (patients, public), and the WHO (political) to address the universal but historically neglected problem of epilepsy. Together the three organisations represent a potentially powerful partnership. Although concerns were expressed about engaging with the WHO, all three organisations proved receptive to this idea, and the first phase of the campaign to bring epilepsy “out of the shadows” was launched in Geneva on June 19, 1997, and in Dublin at the 22nd Epilepsy International Congress on July 3, 1997. The objectives of the Campaign are as follows:

Anticonvulsants and mental symptoms

In his opening paper, Professor Holger Hyd& posed the question whether the brain would ever understand itself? I began to wonder whether, if we did not have any faith or hope in such a possibility, we would ever come to a workshop such as this. On reflection, I decided that I for one would certainly come, if only because of the quality of the hospitality we have received here in Gothenburg. I would, therefore, like to congratulate the organising committee and CI3A-GEIGY for their initiative in arranging the workshop and express my thanks for this excellent hospitality.

Recognition memory in treated epileptic patients

In this study there was no qualitative difference in the performance of a heterogeneous group of epileptic patients and normal subjects on a recognition task for visually presented verbal material. There was, however, a significant overall difference in the number of words recognised. After a statistical correction for V.I.Q. was made this difference disappeared. The small sample size and statistical corrections made on the data make it difficult to draw firm conclusions. The data is part of a pilot study investigating the parameters of the test procedure itself. This test will be used in a carefully controlled, prospective study of the cognitive effects of anticonvulsant drugs.