Multiple nerve excitability measurements were used to investigate axonal membrane properties in patients with chronic renal failure (CRF). Nine patients were studied during routine haemodialysis therapy. The median nerve was stimulated at the wrist and compound muscle action potentials recorded from abductor pollicis brevis. Stimulus-response behaviour, strength-duration time constant, threshold electrotonus, current-threshold relationship and recovery cycle (refractoriness, superexcitability and late subexcitability) were recorded using a recently described protocol. In six patients, sequential studies were performed before, during and after haemodialysis. All patients underwent standard electrolyte and renal function tests before and after haemodialysis. Before dialysis, there were significant abnormalities in axonal excitability: reduced superexcitability; increased accommodation to depolarizing and hyperpolarizing currents; and a steeper current-threshold relationship compared with normal controls. These excitability parameters are the most sensitive to membrane potential and the abnormalities, which were all reduced by haemodialysis, closely resembled those in normal axons depolarized by ischaemia. Before dialysis, the excitability parameters correlated significantly with serum potassium (range 4.3-6.1 mM), but not with other markers of renal dysfunction: patients with normal axonal resting potentials had normal serum potassium, although urea and creatinine were elevated. We conclude that nerves are depolarized in many CRF patients and that the depolarization is primarily due to hyperkalaemia.

Limb girdle muscular dystrophy type 2L or anoctaminopathy is a condition mainly characterized by adult onset proximal lower limb muscular weakness and raised CK values, due to recessive ANO5 gene mutations. An exon 5 founder mutation (c.191dupA) has been identified in most of the British and German LGMD2L patients so far reported. We aimed to further investigate the prevalence and spectrum of ANO5 gene mutations and related clinical phenotypes, by screening 205 undiagnosed patients referred to our molecular service with a clinical suspicion of anoctaminopathy. A total of 42 unrelated patients had two ANO5 mutations (21%), whereas 14 carried a single change. We identified 34 pathogenic changes, 15 of which are novel. The c.191dupA mutation represents 61% of mutated alleles and appears to be less prevalent in non-Northern European populations. Retrospective clinical analysis corroborates the prevalently proximal lower limb phenotype, the male predominance and absence of major cardiac or respiratory involvement. Identification of cases with isolated hyperCKaemia and very late symptomatic male and female subjects confirms the extension of the phenotypic spectrum of the disease. Anoctaminopathy appears to be one of the most common adult muscular dystrophies in Northern Europe, with a prevalence of about 20%-25% in unselected undiagnosed cases.

Objectives: To determine whether patients presenting with a first transient ischaemic attack (TIA) subsequently show increased rates of brain atrophy compared with age matched controls; and to assess potential risk factors for brain atrophy in this group. Methods: 60 patients with a first, isolated TIA and 26 age and sex matched controls were recruited. None had evidence of cognitive impairment. Vascular risk factors were treated appropriately. All subjects had volumetric imaging at the start of the study and one year later, when they were clinically reassessed. TIA patients also had serial dual echo brain imaging. Rates of whole brain atrophy were calculated from the registered volumetric scans, as was the incidence of new ischaemic lesions. In the TIA group, the degree of white matter disease was assessed. Atrophy rates and blood pressure were compared between patients and controls. Results: 22 patients (37%) developed new "clinically silent" infarcts during follow up. The mean (SD) annualised percentage atrophy rate in the TIA group was significantly higher than in the controls, at 0.82 (0.39)% v 0.33 (0.3)% (p < 0.0001). In the TIA group, diastolic blood pressure (p = 0.004) and white matter disease severity (p < 0.001) were correlated with cerebral atrophy rate. Increased white matter disease was found in patients in whom new ischaemic lesions developed (p < 0.001). Conclusions: Patients presenting with a first TIA have excess global brain atrophy compared with age matched controls over the subsequent year. Increased atrophy rates following a TIA may be directly or indirectly related to increasing white matter disease and diastolic hypertension. Future studies should assess whether this atrophy inevitably leads to cognitive decline, and whether aggressive treatment of risk factors for cerebrovascular disease (particularly hypertension) after a TIA can influence outcome. C erebrovascular disease is associated with both cognitive decline and dementia. Cerebrovascular dementia may result from infarction of clinically eloquent cortical sites subserving specific cognitive functions or small, strategic subcortical infarcts (in the thalamus, caudate nucleus, or anterior internal capsule) that disrupt cortico-subcortical pathways.

Background: Haemodialysis may cause neurological symptoms ranging from inconvenient feelings of disequilibrium to life-threatening neurological complications. There are animal data to suggest cerebral swelling may accompany haemodialysis and contribute symptomatically to dialysis disequilibrium. However, MR images acquired following haemodialysis often fail to demonstrate evidence of cerebral oedema. We wished to quantify any potential cerebral volume change which is caused by haemodialysis treatment. Method: Five renal patients and 5 control subjects had a two volumetric T1-weighted MRI scans on the same day. The patients were imaged immediately before and after haemodialysis. None were taking steroids. Precise positional matching (registration) was used to quantify cerebral volume change. Results: Patients had an increase in cerebral volume following dialysis which averaged 32.8 ml (SE 7.4 ml, 3% brain volume). The change in the controls was 1.4 ml (SE 0.6 ml), p < 0.001. No patient had significant neurological symptoms. Conclusion: Cerebral oedema developed in the patients following dialysis. There is a good biological model for these observations. Modifications to dialysis may help. Common problems which increase cerebral volume, e.g. acute stroke, require careful appraisal in these patients. These observations need consideration when quantifying atrophy in dialysis patients.