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Huntington's disease (HD) is a hereditary disorder that typically manifests in adulthood with a combination of motor, cognitive and psychiatric problems. The pathology is caused by a mutation in the huntingtin gene which results in the production of an abnormal protein, mutant huntingtin (mHtt). This protein is ubiquitously expressed and known to confer toxicity to multiple cell types. We have recently reported that HD brains are also characterised by vascular abnormalities, which include changes in blood vessel density/diameter as well as increased blood-brain barrier (BBB) leakage.Objectives: Seeking to elucidate the origin of these vascular and BBB abnormalities, we studied platelets that are known to play a role in maintaining the integrity of the vasculature and thrombotic pathways linked to this, given they surprisingly contain the highest concentration of mHtt of all blood cells.Methods: We assessed the functional status of platelets by performing ELISA, western blot and RNA sequencing in a cohort of 71 patients and 68 age- and sex-matched healthy control subjects. We further performed haemostasis and platelet depletion tests in the R6/2 HD mouse model.Results: Our findings indicate that the platelets in HD are dysfunctional with respect to the release of angiogenic factors and functions including thrombosis, angiogenesis and vascular haemostasis.Conclusion: Taken together, our results provide a better understanding for the impact of mHtt on platelet function. [ABSTRACT FROM AUTHOR]

Background and objectives There have been few studies of long-term outcome in psychogenic nonepileptic seizures (PNES), and none of long-term healthcare utilization. Methods We studied attendance with seizures, healthcare use and employment over a 6-month period from the family doctors of 260 consecutive patients with psychogenic non-epileptic seizures (PNES), 5-10 years after diagnosis. Results We obtained clinical data in 188/260 patients (72.3%), of whom 60 (31.9%) had attended primary or secondary care with seizures in the previous 6 months. Predictors of attendance with seizures included a diagnosis of epilepsy+PNES (OR 5.7, p=0.009), work status (OR 3.9, p=0.027) and social security payments (OR 6.3, p=0.003). Latency to diagnosis was not predictive. Emergency admission data were available in 187 patients, of whom 25 (13.4%) had emergency hospital attendances. Prescription data were available for 172 patients, of whom 154 had 'PNES only'. Of these, 17 (11.0%) remained on antiepileptic medication (AED). 68/172 patients (39.5%) were prescribed antidepressant (AD) drugs. We had psychiatric contact data in 185 patients, of whom 49 (26.5%) had accessed psychiatric services in the last 6 months. Conclusions Surprisingly few of our patients had presented with seizures during the study period. Early reductions in both AED use and healthcare use were sustained long term. Although psychiatric and employment outcomes were less encouraging, some aspects of PNES outcome may be better than previously thought. [ABSTRACT FROM AUTHOR]

Background For patients with psychiatric illnesses remaining refractory to 'standard' therapies, neurosurgical procedures may be considered. Guidelines for safe and ethical conduct of such procedures have previously and independently been proposed by various local and regional expert groups. Methods To expand on these earlier documents, representative members of continental and international psychiatric and neurosurgical societies, joined efforts to further elaborate and adopt a pragmatic worldwide set of guidelines. These are intended to address a broad range of neuropsychiatric disorders, brain targets and neurosurgical techniques, taking into account cultural and social heterogeneities of healthcare environments. Findings The proposed consensus document highlights that, while stereotactic ablative procedures such as cingulotomy and capsulotomy for depression and obsessive-compulsive disorder are considered 'established' in some countries, they still lack level I evidence. Further, it is noted that deep brain stimulation in any brain target hitherto tried, and for any psychiatric or behavioural disorder, still remains at an investigational stage. Researchers are encouraged to design randomised controlled trials, based on scientific and data-driven rationales for disease and brain target selection. Experienced multidisciplinary teams are a mandatory requirement for the safe and ethical conduct of any psychiatric neurosurgery, ensuring documented refractoriness of patients, proper consent procedures that respect patient's capacity and autonomy, multifaceted preoperative as well as postoperative long-term followup evaluation, and reporting of effects and side effects for all patients. Interpretation This consensus document on ethical and scientific conduct of psychiatric surgery worldwide is designed to enhance patient safety. [ABSTRACT FROM AUTHOR]

BACKGROUND: Diagnostic criteria for chronic inflammatory demyelinating polyneuropathy (CIDP) have variable sensitivity and specificity. Newly published criteria by Koski et al combine clinical and electrophysiological components, either of which suffices to establish the diagnosis. European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) criteria require mandatory electrophysiology, as do other sets of criteria. METHODS: The value of the two above-mentioned sets of criteria, on 151 patients with CIDP, and 162 controls with axonal neuropathy, from four European centres was assessed. Results were compared with Van den Bergh and Piéret’s criteria and those of the American Academy of Neurology (AAN). The utility of more extensive nerve-conduction studies was ascertained. RESULTS: Koski et al’s criteria had a sensitivity of 63% and specificity of 99.3%. With unilateral, right-sided, forearm/foreleg, four-nerve studies, EFNS/PNS criteria offered a sensitivity of 81.3% and specificity of 96.2% for "definite/probable" CIDP. Van den Bergh and Piéret’s criteria had a sensitivity of 79.5% and specificity of 96.9%. AAN criteria were poorly sensitive (45.7%) but highly specific (100%). "Possible" electrophysiological CIDP as per EFNS/PNS criteria were poorly specific (69.2%). More extensive studies increased the diagnostic sensitivity of EFNS/PNS criteria (96.7%) but reduced the specificity (79.3%). CONCLUSIONS: In our patient populations, the EFNS/PNS criteria were the most sensitive and allowed identification of a highly significantly greater number of patients than Koski et al’s criteria. The latter were comparable in specificity with the "definite/probable" EFNS/PNS electrodiagnostic subcategories. More extensive nerve-conduction studies improved diagnostic yield but resulted in loss of specificity. [ABSTRACT FROM AUTHOR]

The article presents a response to an article that has been published in the presents issue of the "Journal of Neurology Neurosurgery and Psychiatry," on neurology postgraduate training. In the paper by A J Wills were introduced in the Great Britain in 1997 and the current evaluation is useful from both a Great Britain and a European perspective. The Calman reforms were introduced in the Great Britain in 1997 and the current evaluation is useful from both a Great Britain and a European perspective. These reforms could be generalised within the European Union leading to several recommendations.

Pays tribute to neurologist Fridtjof Nansen. Career history; Achievements; Educational background.

Objective: The safety and tolerability of adjunctive tolcapone initiated simultaneously with levodopa was evaluated with a focus on increases in liver transaminase and hepatotoxicity. Methods: 677 levodopa-naïve patients with early stage Parkinson's disease (PD) were randomised to receive placebo or tolcapone 100 mg three times daily, added to standard doses of levodopa plus carbidopa or benserazide. Results: Increases in liver transaminase above the upper limit of normal (ULN) occurred in 69/342 (20.2%) and 92/335 (27.5%) patients in the placebo and tolcapone groups, respectively. Increases ⩾3 times the ULN occurred in 4/342(1.2%) and 6/335(1.8%) patients receiving placebo and tolcapone, respectively (p=0.5). Liver transaminase values returned to normal in 65% of placebo and 80% of tolcapone treated patients. No instances of serious hepatotoxicity were seen. Diarrhoea was the most commonly reported AE—36/342 (11.0%) placebo v 98/335 (29.0%) tolcapone—and caused discontinuation in 9.9% of tolcapone treated patients. Overall, study discontinuation due to adverse effects was 2.9% in the placebo group and 17.3% in the tolcapone group. Conclusions: Tolcapone seemed to be safe and was generally well tolerated as an adjunctive treatment in patients starting treatment with carbidopa/levodopo for symptomatic PD. Mild increases in transaminase levels—<3 times the ULN—occurred commonly in both placebo and tolcapone treated patients, whereas potentially serious increases of up to ⩾3 times the ULN were infrequent. [ABSTRACT FROM AUTHOR]

Background: Little is known about the long term prognosis for patients the severe acute motor axonal neuropathy (AMAN) form of Guillain-Barre syndrome (GBS), unlike those with acute inflammatory demyelinating neuropathy (AIDP). Objective: To clarify the long term prognosis for patients with AMAN. Methods: Clinical recovery and outcome in 97 consecutive GBS patients were reviewed. Results: Electrodiagnostic criteria showed that 44 patients (45%) had AMAN, 33(34%) had AIDP, and 20 (21%) were unclassified. Most of the severely affected patients had received plasmapheresis or immunoglobulin therapy. Slow recovery (inability to walk independently at six months after onset) was found in six of the AMAN patients (14%) and in two of the AIDP patients (6%). Of the six AMAN patients, four could walk independently one year after the onset, and the other two could walk independently at 28 and 57 months after onset. Of the two AIDP patients, one could walk at nine months after the onset while the other died of pneumonia seven months after onset. Conclusions: AMAN electrodiagnosis is not always a marker of poor recovery. Almost all the severe AMAN patients who had slow recoveries over the first six months could eventually walk independently, although some required several years. [ABSTRACT FROM AUTHOR]

Objective: To measure the effect of deep brain stimulation (DBS) of the subthalamic nucleus in patients with advanced Parkinson's disease.Design: Open label follow up using blinded ratings of videotaped neurological examinations.Patients: 30 patients with advanced Parkinson's disease (19 male, 11 female; mean age 58.8 years; mean disease duration 12.8 years), complicated by intractable wearing off motor fluctuations and dopaminergic dyskinesias.Main Outcome Measures: Unified Parkinson's disease rating scale (UPDRS), part III (motor), score at one year, from blinded reviews of videotaped neurological examinations. Secondary outcomes included the other UPDRS subscales, Hoehn and Yahr scale, activities of daily living (ADL) scale, mini-mental state examination (MMSE), estimates of motor fluctuations and dyskinesia severity, drug intake, and patient satisfaction questionnaire.Results: Subthalamic nucleus stimulation was associated with a 29.5% reduction in motor scores at one year (p<0.0001). The only important predictors of improvement in UPDRS part III motor scores were the baseline response to dopaminergic drugs (p = 0.015) and the presence of tremor (p = 0.027). Hoehn and Yahr scores and ADL scores in the "on" and "off" states did not change, nor did the mean MMSE score. Weight gain occurred in the year after surgery, from (mean) 75.8 kg to 78.5 kg (p = 0.028). Duration of daily wearing off episodes was reduced by 69%. Dyskinesia severity was reduced by 60%. Drug requirements (in levodopa equivalents) declined by 30%.Conclusions: The 30% improvement in UPDRS motor scores was a more modest result than previously reported. DBS did not improve functional capacity independent of drug use. Its chief benefits were reduction in wearing off duration and dyskinesia severity. [ABSTRACT FROM AUTHOR]

Objectives: There has been little research into risk factors for dementia outside Western settings, in particular the importance of early life nutrition as estimated by adult body size. This study investigated the associations of arm and leg length with cognitive impairment and dementia in a community sample of older Korean people. Methods: 746 community residents aged 65 or over were clinically assessed for dementia and cognitive impairment. The following were also measured: arm length (demispan), leg length (iliac crest height), and sitting height (standing height minus iliac crest height). Reproductive history was also ascertained in women. Results: Shorter demispan and leg length were associated with increased age and lower education. They were also associated with dementia and Alzheimer's disease after adjustment for these factors. These associations were only significant in women but were not explained substantially by timing of the menarche or menopause. The association between lower education and dementia was also stronger in women, but was not explained substantially by limb length. Conclusions: Shorter limb length was associated with lower childhood socioeconomic status, as estimated by the presence/duration of formal education. It was also independently associated with dementia and Alzheimer's disease. Sex differences in this association might be explained by gender disadvantage in early life for this cohort or by different associations with health states (for example, cardiovascular disease) later in life. [ABSTRACT FROM AUTHOR]

Objectives: To elucidate the factors associated with severity of cardiac sympathetic nerve involvement in idiopathic Parkinson's disease (PD). Methods: 123I-metaiodobenzylguanidine uptake was examined in 88 patients with PD. The ratio of the uptake in the heart (H) to that in the mediastinum (M) (the H/M ratio) was calculated and correlated with age at onset, age at examination, and disease severity and duration. Twenty five healthy people were also examined as a control. Results: There was a mild but significant negative correlation between H/M ratio and age at onset (early, r = -0.33, p = 0.002; delayed, r = -0.34, p = 0.001) and between Hoehn and Yahr (H-Y) stage (early, r = -0.30, p = 0.006; delayed, r = -0.32, p = 0.003). There was no significant correlation between disease duration and H/M ratio. When patients with PD were classified into four subgroups on the basis of age at onset (> 62 or < 62 years) and disease severity (H-Y > III or H-Y ≤ II), the median H/M ratio of the older and more severe group was significantly lower than that of the younger and less severe group (p = 0.005). Conclusion: This study suggests that late onset, high severity PD is associated with myocardial sympathetic dysfunction. [ABSTRACT FROM AUTHOR]

The article presents information on neurology postgraduate training. In 1992, Kenneth Calman chaired a working group to reform British post-graduate specialist training. These reforms included a reduction in the duration of specialist training, the replacement of the old senior registrar and registrar grades by a combined specialist registrar grade, and the creation of a certificate of completion of specialist training, which would be recognized in all member states of the European Union. The publication of the Calman recommendations preceded high profile media and public criticism of the apparent failure of medical self regulation.

Internet educational tools are often full of fancy graphics displays but short on thought. The Baylor College of Medicine's neurology department's case of the month website is the antithesis of this approach. Each month a case that residents have found interesting is posted on this simple, well thought out site. First a detailed history and examination is presented for each case, from which it is sometimes possible to make a clinical diagnosis. It is usually necessary, however, to proceed to the test result page.