The cognitive and psychomotor effects of remacemide and carbamazepine in newly diagnosed epilepsy.

An international trial comparing remacemide hydrochloride with carbamazepine was undertaken in individuals with newly diagnosed epilepsy using a novel double-blind, parallel-group, double triangular sequential design. Patients with two or more partial or generalized tonic-clonic seizures in the previous year were randomized to remacemide or carbamazepine and titrated to a target dose of 600 mg/day. Subsequent dosage adjustments were allowed while maintaining the blind. Repeated assessments of neuropsychological function and mood were carried out using computerized and conventional measures. The trial was completed 20 months after initiation, following the second interim analysis. Efficacy as measured by seizure recurrence showed remacemide to be inferior to carbamazepine. Baseline cognitive and neuropsychological measures showed impairment across the whole patient population. Cognitive/neuropsychological performance at 8, 24, and 48 weeks was compared with that at baseline. Significant deterioration was seen on measures of information processing speed and attention after treatment with carbamazepine. The study data provide evidence for the utility and sensitivity of a number of cognitive assessments, which may be employed in future trials of antiepileptic drugs.

Long-term safety and efficacy of zonisamide in patients with refractory partial-onset epilepsy.

OBJECTIVES: To investigate whether zonisamide remains effective and well tolerated in the treatment of refractory partial epilepsy during long-term treatment and with flexible dosing in clinical practice. MATERIALS AND METHODS: Patients with refractory partial epilepsy who completed a fixed-dose, randomized, double-blind clinical trial were recruited in an open-label extension study with adjustment of zonisamide and other antiepileptic drug dosage according to the treating physician's usual clinical practice. RESULTS: An intention-to-treat analysis of 317 patients showed that zonisamide was well tolerated with a predictable safety profile. Patient retention rates at 1, 2 and 3 years were 65.3%, 44.5% and 28.8%, respectively. Zonisamide treatment was associated with a maintained reduction in seizure frequency, with some patients achieving prolonged periods of seizure freedom. CONCLUSIONS: Flexible dosing with zonisamide demonstrated a good safety profile and sustained efficacy in the long-term adjunctive treatment of refractory partial epilepsy.

Neuroimaging findings in human prion disease.

Imaging occupies an important role in the investigation of dementia and neurodegenerative disease. The role of imaging in prion disease used to be one of exclusion of other conditions. Over the past decade, the non-invasive nature of MRI, the improved range of magnetic resonance sequences and the availability of clinical and neuropathological correlation have led to a more prominent position of MRI and its inclusion in the diagnostic criteria for variant Creutzfeldt-Jakob disease. As experience of imaging in human prion disease increases, patterns of change related to strain and genotype may improve the diagnostic potential of imaging in the future, may reduce the need for more invasive testing and prove useful in future therapeutic trials. This paper reviews the current knowledge of imaging appearances in human prion disease.

Effects of dose titration on tolerability and efficacy of interferon beta-1b in people with multiple sclerosis.

Multiple sclerosis (MS) treatment with interferon beta is associated with well-known, easily managed adverse events, including influenza-like symptoms and injection-site reactions that decline over time. Initial dose titration has been shown to be one way of limiting these adverse events. Hence, a placebo-controlled, multicentre study of 98 patients was set up to explore whether a slower, four-stage, 4-week titration to a final dose of 250 microg subcutaneous interferon beta-1b might improve tolerability over a more rapid two-stage, 2-week titration in patients with relapsing-remitting MS. Frequency of adverse events was found to be similar between the two regimens: notably, no difference in the incidence of injection-site reactions, with a trend towards fewer influenza-like symptoms in the slow-titration group. Relative to placebo, significantly fewer patients receiving interferon beta-1b relapsed. This was more pronounced in the rapid-titration group than in the slow-titration group, showing that rapid and significant improvements in relapse rates were achieved within 90 days of starting interferon beta-1b. Although a rapid-titration regimen results in a quicker onset of clinical benefit, slow titration showed a non-significant trend towards reduced influenza-like symptoms.

Accelerated forgetting in patients with epilepsy: evidence for an impairment in memory consolidation.

Patients with epilepsy frequently complain of memory difficulties yet perform normally on standard neuropsychological tests of memory. It has been suggested that this may be due to an impairment of very long-term memory consolidation processes, beyond those normally assessed in the neuropsychological clinic. We carried out a prospective study of verbal memory over a long-term retention interval of 8 weeks in patients with epilepsy and in controls. Results were compared with performance on conventional tests of memory. Despite normal learning and retention over 30 min, patients with epileptic foci in the left temporal lobe performed disproportionately poorly on the long-term test compared with both patients with epileptic foci in the right temporal lobe and controls. Our findings provide evidence for an extended period of memory consolidation and point to the critical region for this process, at least for verbal material, in the left temporal lobe. The implications of our findings for clinical assessment and therapeutic management of patients with epilepsy are discussed.

Gabapentin does not affect antipyrine clearance.

The effect of gabapentin on antipyrine clearance was assessed in 12 healthy male volunteers, using a known enzyme inducer, phenytoin, as control. Subjects received gabapentin 400 mg or phenytoin 100 mg three times daily for 2 weeks. Antipyrine tests were performed before, during, and after treatment with gabapentin or phenytoin. In contrast to phenytoin, chronic administration of gabapentin did not affect antipyrine clearance. Gabapentin appears to have little potential for drug interactions.

Is stroke incidence related to season or temperature? The Oxfordshire Community Stroke Project.

BACKGROUND: A winter excess of ischaemic stroke has been found in mortality and hospital-based studies. It is often assumed that this is due to seasonal variation in stroke incidence and several pathophysiological explanations have been proposed. We studied the incidence of stroke in relation to season and outside temperature. METHODS: The data came from a community-based study of first ever in a lifetime stroke in a defined population of about 105 000. 675 such strokes were registered over four years and the month of inset was analysed separately for cerebral infarction, primary intracerebral haemorrhage, and subarachnoid haemorrhage. FINDINGS: There was no significant seasonal variation. The incidence of primary intracerebral haemorrhage was increased at low temperatures, but there was no significant relation between the incidence of ischaemic stroke or subarachnoid haemorrhage and temperature. INTERPRETATION: The widely reported winter excess of ischaemic strokes may be an artifact due to referral bias in hospital-based studies and increased case fatality during the winter in mortality studies.

The identification of presymptomatic parkinsonism: clinical and [18F]dopa positron emission tomography studies in an Irish kindred.

An Irish kindred is described in which 5 of 10 siblings in the fourth or fifth decade of life developed an akinetic-rigid syndrome clinically indistinguishable from idiopathic Lewy body Parkinson's disease. Four of these patients were scanned by positron emission tomography (PET) with [18F]dopa after clinical diagnosis and in all, a profound impairment of tracer uptake into the striatum was recorded. The fifth patient was initially scanned at a time when he was asymptomatic and normal by clinical examination. His scan showed impaired tracer uptake, indicating a subclinical defect in the presynaptic nigrostriatal system. Within months of his scan, he too developed subtle symptoms and signs of parkinsonism although there was little further clinical progression or change in his PET scan over the following year. A clinically normal sibling was also scanned and found to have subclinical impairment of [18F]dopa uptake in the putamen. The 19-year-old daughter of an affected sibling had a mild postural tremor but no other symptoms or signs. The [18F]dopa uptake in her putamen fell at the borderline between normal and parkinsonian values. This study confirms that PET can identify preclinical parkinsonism in at-risk subjects. The finding of abnormalities in several clinically unaffected family members suggests that family studies based on clinical assessment alone may miss a significant number of subclinically affected individuals, leading to an underestimate of any genetic component to Parkinson's disease.

Sinus histiocytosis with massive lymphadenopathy--isolated suprasellar involvement.

An unusual case of an isolated histioproliferative lesion arising from the suprasellar region is described. The presence of lymphophagocytosis suggested that this represented an extranodal intracranial form of sinus histiocytosis with massive lymphadenopathy.

Diurnal variation in incidence of stroke: Oxfordshire community stroke project.

OBJECTIVE: To determine whether diurnal variation occurs in the onset of stroke. DESIGN: Community based study over four years. SETTING: Oxfordshire, United Kingdom. SUBJECTS: 105,000 people, of whom 675 had a first ever stroke. 545 had a cerebral infarction, 66 had primary intracerebral haemorrhage, 33 had subarachnoid haemorrhage, and in 31 the type of stroke was not known. MAIN OUTCOME MEASURES: Time of stroke and degree of activity at onset. RESULTS: In the 578 patients for whom it was known whether onset occurred while asleep or awake, the proportion with onset during sleep was 25% (135/545) for cerebral infarction, 17% (11/66) for primary intracerebral haemorrhage, and 0% (0/33) for subarachnoid haemorrhage. This difference persisted if patients in whom it was not known whether they were asleep or awake at onset were classed as asleep. For all stroke types together there was a significant (chi 2 = 218.7, p less than 0.001) diurnal variation with a morning peak between 0800 and 1000, which persisted even after allowing for strokes first noted on waking by redistributing the hour of onset through the preceding eight hours (chi 2 = 47, p less than 0.001). A significant diurnal variation was also found in the onset of cerebral infarction (peak 0800-1000, chi 2 = 208.4, p less than 0.001). Fewer patients had other forms of stroke and the diurnal variations for primary intracerebral haemorrhage (peak 1000-1200) and subarachnoid haemorrhage (peaks 0800-1000 and 1800-2000) were not significant. There seemed to be a second smaller peak for all types of stroke. CONCLUSIONS: All types of stroke are most likely to occur after waking in the morning. The cause of the circadian variation requires further study.

Painful intraorbital meningiomas.

Three cases are reported of meningioma involving the orbital apex presenting with either progressive or episodic retroocular pain. In two cases pain was steroid responsive and in one of these patients this led to an initial diagnosis of orbital pseudotumour. Pain preceded visual loss and other symptoms by many months and these cases illustrate the importance of full investigation and where necessary surgical exploration in cases of apparent orbital inflammatory disease with an atypical or progressive course.

Whipple's disease confined to the CNS presenting with multiple intracerebral mass lesions.

A patient with isolated cerebral Whipple's disease presented with signs of raised intracranial pressure and multiple ring enhancing intracerebral mass lesions evident on CT and MRI imaging. Characteristic intracellular bacilliform inclusions were identified in a brain biopsy. Clinical improvement followed treatment with parenteral antibiotics for two weeks and long term sulphamethoxazole-trimethoprim. As CNS relapse of Whipple's disease may occur after several years, long term treatment should include antibiotics that are able to cross the blood-brain barrier.

Cerebrospinal fluid oligoclonal IgM in multiple sclerosis: analytical problems and clinical limitations.

A method for detecting cerebrospinal fluid (CSF) oligoclonal IgM is described. Concentrated CSF was separated by agarose isoelectric-focusing and blotted with poly(vinyldifluoride). A double-antibody immunoperoxidase technique with avidin-biotin amplification was used to stain IgM. Special conditions were required to avoid cross-reaction with IgG. The method was applied to 99 patients on whom oligoclonal IgG analysis was performed. Positive IgM results occurred in 17 of the 27 patients positive for oligoclonal IgG, and in two patients negative for oligoclonal IgG, neither of whom had multiple sclerosis (MS). Fifteen of the patients positive for oligoclonal IgM had some IgM bands in their sera. Oligoclonal IgM was not found in the CSF of suspected MS patients without oligoclonal IgG, but occurred in several patients with oligoclonal IgG due to other diseases. As a test for MS, oligoclonal IgM was less sensitive than oligoclonal IgG and did not improve specificity.

Migraine occurring for the first time in pregnancy.

Nine patients referred for neurological opinion over a 4 yr. period were identified as having migraine occurring for the first time with pregnancy. The nature of their attacks, results of investigation, the progress of the pregnancy and the prognosis for headache post-partum are presented. One patient had common migraine, the remainder, either classical or complicated attacks. Patients presented at variable stages of pregnancy; four developed complications, including pre-eclamptic toxemia in two. The prognosis for headache during the follow up period of up to 54 months was excellent. The factors influencing migraine in pregnancy are discussed.

Oligoclonal bands and the IgG index in multiple sclerosis: uses and limitations.

The relationship between two tests commonly used in the investigation of multiple sclerosis (MS), the IgG index and oligoclonal bands, has been assessed. Using an immunoblotting technique specific for IgG, analysis of cerebrospinal fluid for oligoclonal bands was found to provide greater diagnostic sensitivity than the IgG index without any loss of specificity. In patients without oligoclonal bands the IgG index had no diagnostic value for MS and in the presence of bands the magnitude of the index was unrelated to the clinical certainty of the diagnosis. High values of the IgG index were invariably associated with the presence of oligoclonal bands and the IgG index appeared to have no clinical significance independent of this relationship. Even as a screening test the IgG index has serious limitations.

The clinical value of serum prolactin measurement in the differential diagnosis of complex partial seizures.

The time course of changes in serum prolactin after complex partial seizures has been determined and compared to similar changes after other types of seizure and non-epileptic attacks. Seizures in 33 subjects were recorded on video EEG telemetry. Peak serum prolactin concentrations occurred 15-20 min after tonic-clonic seizures, 10 min after complex partial seizures, and were highest after generalised tonic-clonic seizures. Serum prolactin concentrations remained less than 1000 mU/l after absences and non-epileptic attacks. Application of Bayes' theorem showed that where serum prolactin was greater than 1000 mU/l 5-10 min post event this would identify genuine tonic-clonic or complex partial seizures. The false negative rate of this test was 9% for tonic-clonic seizures and 38% for complex partial seizures. Failure of serum prolactin to rise after an attack is of little value in distinguishing complex partial seizures from non-epileptic attacks.