[Does ECT raise the risk of a recurrent stroke?] / Vormt ECT een risico op een recidief van cerebrovasculair accident?

BACKGROUND: As the guidelines and evidence for the use of electroconvulsive therapy (ECT) in patients with a recent or past history of stroke are unclear, ECT tends to be avoided in this population. AIM: To give a systematic review the literature on the risk and incidence of cerebrovascular accidents after ECT in these patients. METHOD: A systematic literature search was performed according to the PRISMA guidelines in PubMed and in the Cochrane Library. Publications in which ECT was applied in patients with a history of stroke were included by using specific MeSH terms. RESULTS: The following 19 articles met the criteria for review: 1 wide-scale prospective study, 1 small-scale prospective study with a control group, 3 small-scale retrospective studies, and 14 case reports. In the vast longitudinal Danish study, ECT was not associated with an elevated risk of recurrent stroke. Similarly, none of the other studies found the risk to be raised. CONCLUSION: Despite the limited number of prospective studies and the methodological discrepancies in the reports, ECT does not seem to be associated with an elevated risk of recurrent stroke. This review supports the safe use of ECT in patients with a recent or past history of stroke, if prior neurologic and cardiovascular assessments are being performed, as well as monitoring during the treatment.

HIV sero-positivity and risk factors for ischaemic and haemorrhagic stroke in hospitalised patients in Uganda: A prospective-case-control study.

Objectives: We examined HIV sero-positivity and risk factors in patients admitted with ischaemic stroke (IS) and haemorrhagic stroke (HS) in Kampala, Uganda. Study design: We conducted a matched case-control study between December 2016 and December 2018 â€‹at â€‹St Francis Hospital, Nsambya. Methods: The study population comprised of stroke cases (adults aged ≥18 years with IS or HS confirmed by neuroimaging) and controls (age- and sex-matched stroke-free adults aged ≥18 years who were recruited from the same hospital as the cases). A comprehensive assessment for sociodemographic, lifestyle and clinical factors was performed using the World Health Organization (WHO) STEP-wise approach to Surveillance (STEPS) for stroke risk factor surveillance. We used conditional logistic regression to identify risk factors associated with IS or HS. Results: We enrolled 137 matched case-control pairs; 48 (35%) were men, and the mean ages were 62.4 years (SD â€‹± â€‹14.8) for cases and 61.1 years (SD â€‹± â€‹14.1) for controls. Of stroke patients, 86 (63%) had IS and 51 (37%) had HS. Overall, HIV sero-positivity was 10% among stroke cases versus 7% among controls. HIV sero-positivity was not significantly associated with stroke (unadjusted odds ratio [uOR] â€‹= â€‹1.49, 95% confidence interval [CI] 0.59-3.78). A self-reported family history of diabetes mellitus was associated with an increased risk of all stroke (adjusted odds ratio [aOR] â€‹= â€‹4.41, 95% CI 1.47-13.2), as well as for IS and HS separately (aOR â€‹= â€‹3.66, 95% CI 1.09-12.4 and aOR â€‹= â€‹4.99, 95% CI 1.02-24.4, respectively). High blood pressure (≥140/90 â€‹mmHg) was associated with an increased risk of all stroke (aOR â€‹= â€‹12.3, 95% CI 42-44.1), and this was also true for IS and HS individually (aOR â€‹= â€‹6.48, 95% CI 1.15-36.7 and aOR â€‹= â€‹5.63, 95% CI 1.74-18.2, respectively). Conclusions: No association was found between HIV sero-positivity and stroke occurrence among Ugandan stroke patients. Hypertension and a self-reported family history of diabetes mellitus were significant risk factors for both IS and HS. Interventions to reduce hypertension and diabetes mellitus in the Ugandan population are urgently required. Much larger studies are required to demonstrate if any association exists between HIV and stroke.

Stroke coach: a pilot study of a personal digital coaching program for patients after ischemic stroke.

Despite recent advances in acute stroke care, the risk of recurrent stroke remains high. On behalf of the Belgian Stroke Council (BSC), a nurse-led self-management program was developed, using a personal coach and digital platform with the aim of improving cardiovascular risk factor control in patients after ischemic stroke. The program was implemented in four Belgian hospitals. The stroke coach provided one educational session during hospitalization. After discharge, the patient received tips and tricks concerning a healthy lifestyle through the customized platform. The stroke coach set up video appointments through the platform at regular intervals. Primary endpoint of our study was the change in SCORE (Systematic COronary Risk Evaluation: High and Low cardiovascular Risk Charts) risk at baseline and 6 months compared with a historical control group who received standard care. A total of 147 patients were included for a follow-up period of 6 months. The mean SCORE in the intervention group showed a statistically significant reduction of 3.2 (p < 0.001) at 6 months. However, comparison between control and intervention groups was non-significant (p = 0.55). Secondary endpoints are promising with a medication adherence of 96%. Reported quality of life also improved (p < 0.001). No significant improvement in the modified Rankin scale (mRS) was observed (p = 0.720). Five percent of patients suffered a recurrent stroke. Our project consisting of a coached lifestyle intervention and digital platform shows promise in improving stroke recurrence rates, therapeutic adherence and quality of life in a Belgian healthcare setting.

Postural control and the relation with cervical sensorimotor control in patients with idiopathic adult-onset cervical dystonia.

Cervical dystonia (CD) is a movement disorder characterized by involuntary muscle contractions leading to an abnormal head posture or movements of the neck. Dysfunctions in somatosensory integration are present and previous data showed enlarged postural sway in stance. Postural control during quiet sitting and the correlation with cervical sensorimotor control were investigated. Postural control during quiet sitting was measured via body sway parameters in 23 patients with CD, regularly receiving botulinum toxin treatment and compared with 36 healthy controls. Amplitude and velocity of displacements of the center of pressure (CoP) were measured by two embedded force plates at 1000 Hz. Three samples of 30 s were recorded with the eyes open and closed. Disease-specific characteristics were obtained in all patients by the Tsui scale, Cervical Dystonia Impact Profile (CDIP-58) and Toronto Western Spasmodic Rating Scale (TWSTRS). Cervical sensorimotor control was assessed with an infrared Vicon system during a head repositioning task. Body sway amplitude and velocity were increased in patients with CD compared to healthy controls. CoP displacements were doubled in patients without head tremor and tripled in patients with a dystonic head tremor. Impairments in cervical sensorimotor control were correlated with larger CoP displacements (rs ranged from 0.608 to 0.748). Postural control is impaired and correlates with dysfunction in cervical sensorimotor control in patients with CD. Treatment is currently focused on the cervical area. Further research towards the potential value of postural control exercises is recommended.

Sensory processing and central pain modulation in patients with chronic shoulder pain: A case-control study.

Chronicity and recurrence in musculoskeletal shoulder pain are highly prevalent and can possibly be attributed to the concept of central sensitization. Available studies suggest a role for central sensitization in explaining chronic shoulder pain, but so far a comprehensive quantitative sensory testing (QST) protocol has not been used. The aim of this study was to gain knowledge on sensory processing and central pain modulatory mechanisms in patients suffering from chronic shoulder pain using such a QST protocol. Fifty study participants, including chronic shoulder pain patients and healthy controls, underwent a standardized, comprehensive psychophysical testing procedure. A static adapted QST protocol (including pressure algometry, vibration and mechanical detection) was applied. Thereafter, all subjects underwent dynamic measures of temporal summation and conditioned pain modulation. Questionnaires assessing psychosocial factors were completed by each subject. No significant differences (P >= .05) were found between patients and controls based on pressure algometry, vibration detection, mechanical detection, temporal summation, and conditioned pain modulation. Moderate positive correlations (r = .5) were found between pressure pain thresholds (PPTs) and the amount of sports participation. Weak-to-moderate negative correlations (r = -.3 à -.5) were found between PPTs and psychosocial factors such as pain catastrophizing. Based on these findings, we can conclude that central sensitization is no characteristic feature in chronic musculo-skeletal shoulder pain but can be present in individual cases.

The C9orf72 repeat size correlates with onset age of disease, DNA methylation and transcriptional downregulation of the promoter.

Pathological expansion of a G4C2 repeat, located in the 5' regulatory region of C9orf72, is the most common genetic cause of frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). C9orf72 patients have highly variable onset ages suggesting the presence of modifying factors and/or anticipation. We studied 72 Belgian index patients with FTLD, FTLD-ALS or ALS and 61 relatives with a C9orf72 repeat expansion. We assessed the effect of G4C2 expansion size on onset age, the role of anticipation and the effect of repeat size on methylation and C9orf72 promoter activity. G4C2 expansion sizes varied in blood between 45 and over 2100 repeat units with short expansions (45-78 units) present in 5.6% of 72 index patients with an expansion. Short expansions co-segregated with disease in two families. The subject with a short expansion in blood but an indication of mosaicism in brain showed the same pathology as those with a long expansion. Further, we provided evidence for an association of G4C2 expansion size with onset age (P<0.05) most likely explained by an association of methylation state of the 5' flanking CpG island and expansion size in blood (P<0.0001) and brain (P<0.05). In several informative C9orf72 parent-child transmissions, we identified earlier onset ages, increasing expansion sizes and/or increasing methylation states (P=0.0034) of the 5' CpG island, reminiscent of disease anticipation. Also, intermediate repeats (7-24 units) showed a slightly higher methylation degree (P<0.0001) and a decrease of C9orf72 promoter activity (P<0.0001) compared with normal short repeats (2-6 units). Decrease of transcriptional activity was even more prominent in the presence of small deletions flanking G4C2 (P<0.0001). Here we showed that increased methylation of CpGs in the C9orf72 promoter may explain how an increasing G4C2 size lead to loss-of-function without excluding repeat length-dependent toxic gain-of-function. These data provide insights into disease mechanisms and have important implications for diagnostic counseling and potential therapeutic approaches.

[Psychogenic movement disorders]. / Psychogene bewegingsstoornissen.

BACKGROUND: Psychogenic movement disorders are movement disorders that are the result of a psychiatric rather than a primary neurological disorder. Some authors prefer the term 'functional movement disorder'. AIM: To discuss the nosology, clinical signs, diagnosis and treatment of psychogenic movement disorders. METHOD: We discuss recent, selected literature. RESULTS: Patients with psychogenic movement disorders have debilitating symptoms that can lead to long-term disability. Often such patients are diagnosed with 'conversion disorder'. There is evidence that stress can interfere with motor functioning by affecting centres that are involved in planning and action monitoring. These patients need structured and multidisciplinary treatment supported by neurological and psychiatric follow-up. Cognitive behavioral therapy and low-frequency transcranial magnetic stimulation have a limited effect. CONCLUSION: Psychogenic movement disorders and conversion disorders have features in common. There is evidence that cognitive behavioral therapy has beneficial effects, but the prognosis remains poor.

Methadone-induced toxic leukoencephalopathy: MR imaging and MR proton spectroscopy findings.

We report the clinical, MR imaging, and proton MR spectroscopy findings in a middle-aged woman with proved methadone-induced toxic leukoencephalopathy. The imaging characteristics of this unusual condition have been reported only rarely in the medical literature. We show that the imaging findings in methadone-induced toxic leukoencephalopathy are similar, though not identical, to previously reported cases of neurologic deterioration due to heroin inhalation.

Updated clinical diagnostic criteria for sporadic Creutzfeldt-Jakob disease.

Several molecular subtypes of sporadic Creutzfeldt-Jakob disease have been identified and electroencephalogram and cerebrospinal fluid biomarkers have been reported to support clinical diagnosis but with variable utility according to subtype. In recent years, a series of publications have demonstrated a potentially important role for magnetic resonance imaging in the pre-mortem diagnosis of sporadic Creutzfeldt-Jakob disease. Magnetic resonance imaging signal alterations correlate with distinct sporadic Creutzfeldt-Jakob disease molecular subtypes and thus might contribute to the earlier identification of the whole spectrum of sporadic Creutzfeldt-Jakob disease cases. This multi-centre international study aimed to provide a rationale for the amendment of the clinical diagnostic criteria for sporadic Creutzfeldt-Jakob disease. Patients with sporadic Creutzfeldt-Jakob disease and fluid attenuated inversion recovery or diffusion-weight imaging were recruited from 12 countries. Patients referred as 'suspected sporadic Creutzfeldt-Jakob disease' but with an alternative diagnosis after thorough follow up, were analysed as controls. All magnetic resonance imaging scans were assessed for signal changes according to a standard protocol encompassing seven cortical regions, basal ganglia, thalamus and cerebellum. Magnetic resonance imaging scans were evaluated in 436 sporadic Creutzfeldt-Jakob disease patients and 141 controls. The pattern of high signal intensity with the best sensitivity and specificity in the differential diagnosis of sporadic Creutzfeldt-Jakob disease was identified. The optimum diagnostic accuracy in the differential diagnosis of rapid progressive dementia was obtained when either at least two cortical regions (temporal, parietal or occipital) or both caudate nucleus and putamen displayed a high signal in fluid attenuated inversion recovery or diffusion-weight imaging magnetic resonance imaging. Based on our analyses, magnetic resonance imaging was positive in 83% of cases. In all definite cases, the amended criteria would cover the vast majority of suspected cases, being positive in 98%. Cerebral cortical signal increase and high signal in caudate nucleus and putamen on fluid attenuated inversion recovery or diffusion-weight imaging magnetic resonance imaging are useful in the diagnosis of sporadic Creutzfeldt-Jakob disease. We propose an amendment to the clinical diagnostic criteria for sporadic Creutzfeldt-Jakob disease to include findings from magnetic resonance imaging scans.

MRI lesion profiles in sporadic Creutzfeldt-Jakob disease.

BACKGROUND: With respect to sporadic Creutzfeldt-Jakob disease (sCJD), six molecular subtypes (MM1, MM2, MV1, MV2, VV1, and VV2) have been described, which vary with respect to age at disease onset, disease duration, early symptoms, and neuropathology. MRI signal alterations were reported to correlate with distinct Creutzfeldt-Jakob disease (CJD) subtypes. This multicenter, international study aimed to describe the brain MRI findings associated with each of the sCJD molecular subtypes. METHODS: Pathologically confirmed sCJD cases with codon 129 genotype (MM, MV, and VV), PrP(Sc) type, and fluid-attenuated inversion recovery (FLAIR) or diffusion-weighted imaging (DWI) were collected in seven countries. All MRI scans were assessed for signal changes according to a standard protocol encompassing seven cortical regions, basal ganglia, thalamus, and cerebellum. RESULTS: MRI scans were evaluated in 211 CJD patients (98 MM1, 23 MM2, 19 MV1, 30 MV2, 9 VV1, and 32 VV2). Basal ganglia hyperintensities occurred most frequently in MV2, VV2, and MM1 subtypes (79, 77, and 70%). Wide cerebral cortical signal increase was most common in VV1, MM2, and MV1 subtypes (86, 77, and 77%). Thalamic hyperintensities occurred most often in VV2 (45%) and MV2 (43%). The most consistent finding across most subtypes was high signal in basal ganglia, with these abnormalities found in 63% (FLAIR) and 71% (DWI). CONCLUSION: Cortical signal increase and hyperintensities in the basal ganglia and thalamus are detected by MRI across all molecular sporadic Creutzfeldt-Jakob disease subtypes. Our findings argue that characteristic MRI lesion patterns may occur for each molecular subtype.

Organ procurement after euthanasia: Belgian experience.

Euthanasia was legalized in Belgium in 2002 for adults under strict conditions. The patient must be in a medically futile condition and of constant and unbearable physical or mental suffering that cannot be alleviated, resulting from a serious and incurable disorder caused by illness or accident. Between 2005 and 2007, 4 patients (3 in Antwerp and 1 in Liège) expressed their will for organ donation after their request for euthanasia was granted. Patients were aged 43 to 50 years and had a debilitating neurologic disease, either after severe cerebrovascular accident or primary progressive multiple sclerosis. Ethical boards requested complete written scenario with informed consent of donor and relatives, clear separation between euthanasia and organ procurement procedure, and all procedures to be performed by senior staff members and nursing staff on a voluntary basis. The euthanasia procedure was performed by three independent physicians in the operating room. After clinical diagnosis of cardiac death, organ procurement was performed by femoral vessel cannulation or quick laparotomy. In 2 patients, the liver, both kidneys, and pancreatic islets (one case) were procured and transplanted; in the other 2 patients, there was additional lung procurement and transplantation. Transplant centers were informed of the nature of the case and the elements of organ procurement. There was primary function of all organs. The involved physicians and transplant teams had the well-discussed opinion that this strong request for organ donation after euthanasia could not be waived. A clear separation between the euthanasia request, the euthanasia procedure, and the organ procurement procedure is necessary.

Organisation of inhospital acute stroke care and minimum criteria for stroke care units. Recommendations of the Belgian Stroke Council.

There is ample evidence from randomized trials that for patients with stroke, stroke unit care is superior to care in general medical or neurological wards. This evidence, which has been adopted by international guidelines has to be implemented into daily stroke care. This consensus document prepared by the Belgian Stroke Council provides a set of minimum criteria to meet international standards for stroke care. It is intended to provide help in the creation of stroke units in centers who do not currently have one and to provide a benchmark for centres already having organised stroke care.

Progranulin variability has no major role in Parkinson disease genetic etiology.

BACKGROUND: Different loss-of-function mutations were identified underlying PGRN haploinsufficiency in patients with frontotemporal lobar degeneration. PGRN mutations were also identified in other neurodegenerative brain diseases such as amyotrophic lateral sclerosis and Alzheimer disease, though their biologic contribution to these diseases remains elusive. Because of its apparent role in neuronal survival, we argued that PGRN might also contribute to Parkinson disease (PD) pathogenesis. METHODS: We screened PGRN exons for mutations in 255 patients with PD and 459 control individuals by direct genomic sequencing. Genetic association of PGRN with risk for PD was assessed using single nucleotide polymorphisms (SNPs) across the gene. RESULTS: In patients we identified four missense mutations of which p.Asp33Glu and p.Arg514Met were absent in control individuals. Single SNP and haplotype analyses did not detect significant associations with PD. CONCLUSIONS: Our results do not support a major role for PGRN in the genetic etiology of Parkinson disease (PD). At this stage and in the absence of functional data, it remains unclear whether p.Asp33Glu and p.Arg514Met are biologically relevant to PD pathogenesis in the mutation carriers.

Lrrk2 R1441C parkinsonism is clinically similar to sporadic Parkinson disease.

OBJECTIVE: Leucine-rich repeat kinase 2 (LRRK2) mutations are the most common cause of Parkinson disease (PD). Several dominantly inherited pathogenic substitutions have been identified in different domains of the Lrrk2 protein. Herein, we characterize the clinical and genetic features associated with Lrrk2 p.R1441C. METHODS: We identified 33 affected and 15 unaffected LRRK2 c.4321C>T (p.R1441C) mutation carriers through an international consortium originating from three continents. The age-specific cumulative incidence of PD was calculated by Kaplan-Meier analysis. RESULTS: The clinical presentation of Lrrk2 p.R1441C carriers was similar to sporadic PD and Lrrk2 p.G2019S parkinsonism. The mean age at onset for parkinsonism was 60 years, range 30-79 years; fewer than 20% of the patients had symptoms before the age 50 years, while by 75 years >90% of them had developed symptoms. Haplotype analysis suggests four independent founders for the p.R1441C mutation. CONCLUSIONS: The distribution in age at onset and clinical features in Lrrk2 p.R1441C patients are similar to idiopathic and Lrrk2 p.G2019S parkinsonism. Several independent founders of the p.R1441C substitution suggest this site is prone to recurrent mutagenesis.

Campylobacter jejuni-induced acute transverse myelitis.

STUDY DESIGN: Case report. SETTING: University Hospital of Antwerp, tertiary referral hospital of the University of Antwerp, Edegem, Belgium. CASE REPORT: Campylobacter jejuni infection is related to various syndromes in which the peripheral nervous system is involved. An immune response is triggered through molecular mimicry between gangliosides of the peripheral nervous system and lipo-oligosaccharides of C. jejuni. We report a case of a previously healthy 17-year-old girl, who developed clinical manifestations of acute transverse myelitis (ATM) 7 days after a culture-proven C. jejuni enteritis. High titres of serum IgG antibodies to the ganglioside GM1 were found in the acute phase of disease, which decreased with clinical recovery. These antibodies cross-reacted with C. jejuni lipo-oligosaccharides, indicating that C. jejuni infections may induce ATM. CONCLUSIONS: Only a few cases of C. jejuni infection associated with demyelination of the central nervous system or spinal cord have been described. Physicians should be aware that C. jejuni might be another cause of transverse myelitis.

Posterior reversible encephalopathy and Guillain-Barré syndrome in a single patient: coincidence or causative relation?

We report 62-year-old female patient with coincident posterior reversible encephalopathy syndrome (PRES) and Guillain-Barré syndrome (GBS). The first presentation of PRES was a generalised tonic-clonic seizure. A risk factor for PRES was acute arterial hypertension. The diagnosis of PRES was established by MRI (magnetic resonance imaging) and hypertension was treated with labetalol 800mg daily followed by regression of symptoms of PRES. Two days after the seizure the first motor signs of GBS presented with a weakness in both upper arms. The diagnosis of GBS was finally established 6 days after the seizure by clinical evolution, lumbar puncture and electrophysiological findings. After treatment of GBS with intravenous immunoglobulins (IVIg), antihypertensive therapy could be phased out and finally stopped. The patient was discharged after 25 days without any medication. At that time she was completely recovered from PRES and recovering well from GBS. The acute arterial hypertension, the provoking factor of PRES, was probably caused by an autonomic dysfunction in the context of GBS before motor signs of GBS were present but we speculate also that there are other GBS related factors playing a role in PRES. This hypothesis is based on the relatively high coincidence of these two rare syndromes which appears from a review of the literature. One other possible mechanism can be the influence of cytokines, produced in the context of a GBS, on the permeability of blood brain barrier.

Opsoclonus-myoclonus syndrome: a clinicopathological confrontation.

Opsoclonus-myoclonus syndrome (OMS), a movement disorder characterised by chaotic eye movements and myoclonus, is a rare clinical entity. We present two cases of opsoclonus-myoclonus syndrome of paraneoplastic origin. In the first patient the syndrome was associated with a breast carcinoma and in the second patient with a non small cell lung carcinoma. However none of the commonly associated antibodies were found in these cases. From the neuropathological findings from the first patient we find arguments that support the current hypothesis on the pathophysiology of OMS namely a dysfunction in brainstem and cerebellum. We conclude that in adults with OMS one has to be very suspicious of a possible neoplastic origin of the syndrome. The antibodies associated with some cases of OMS are thought to play a role in the pathophysiology of the syndrome although the exact immunologic mechanism remains unknown. Research into the neuropathological substrate of OMS yields a broad range of abnormalities in brain stem and cerebellum. However none of these findings seem to be pathognomonic. As for the possible therapy of OMS, several immunomodulating strategies can be used with varying success. At present there is no established standard therapy.

Increased incidence of sporadic Creutzfeldt-Jakob disease in the age groups between 70 and 90 years in Belgium.

From 1998 a prospective surveillance study of Creutzfeldt-Jakob disease (CJD) has been initiated in Belgium. In addition to epidemiological data, information on cerebrospinal fluid biomarkers, prion protein gene and brain neuropathology was collected. From 1-1-1998 to 31-12-2004, 188 patients were referred to the surveillance system. In 85 patients a 'definite' diagnosis of sporadic CJD (sCJD) could be made, whereas 26 patients remained 'probable'. We further identified two unrelated patients with an E200K mutation, and two patients with a seven octapeptide repeat insertion in one family. In one patient a familial history was noted but genetic analysis was not performed. In 72 patients different final diagnoses were made, Alzheimer's disease being the most frequent (N = 20). The demographic parameters of the Belgian population were similar to those observed in the rest of Europe. We did notice a significantly increased age-specific incidence (> 6/10(6)/year) of sCJD patients between 70 and 90 years old in the period 2002-2004 compared to 1998-2001 and retrospectively obtained data (1990-1997, p < 0.01). We undertook a detailed clinical and biochemical analysis to investigate this increase but could not identify any reason other than an increased vigilance for the diagnosis. In conclusion, our study identified that in the past sCJD may have been underestimated in patients over age 70 although these patients are both clinically and neurobiochemically similar to the general sCJD phenotype.

Frameshift proteins in autosomal dominant forms of Alzheimer disease and other tauopathies.

Frameshift (+1) proteins such as APP(+1) and UBB(+1) accumulate in sporadic cases of Alzheimer disease (AD) and in older subjects with Down syndrome (DS). We investigated whether these proteins also accumulate at an early stage of neuropathogenesis in young DS individuals without neuropathology and in early-onset familial forms of AD (FAD), as well as in other tauopathies, such as Pick disease (PiD) or progressive supranuclear palsy (PSP). APP(+1) is present in many neurons and beaded neurites in very young cases of DS, which suggests that it is axonally transported. In older DS patients (>37 years), a mixed pattern of APP(+1) immunoreactivity was observed in healthy looking neurons and neurites, dystrophic neurites, in association with neuritic plaques, as well as neurofibrillary tangles. UBB(+1) immunoreactivity was exclusively present in AD type of neuropathology. A similar pattern of APP(+1) and UBB(+1) immunoreactivity was also observed for FAD and much less explicit in nondemented controls after the age of 51 years. Furthermore, we observed accumulation of +1 proteins in other types of tauopathies, such as PiD, frontotemporal dementia, PSP and argyrophylic grain disease. These data suggest that accumulation of +1 proteins contributes to the early stages of dementia and plays a pathogenic role in a number of diseases that involve the accumulation of tau.

Cerebrospinal fluid biomarkers in Creutzfeldt-Jakob disease.

Creutzfeldt-Jakob disease (CJD) is a rare neurodegenerative disorder. Since the emergence of variant CJD (vCJD) vigilance concerning the disease's incidence has increased and the interest in accurate in vivo diagnosis has augmented. So far, a large number of biomarkers has been investigated as aid in the differential diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD) and vCJD. These include, among others, neuron-specific enolase (NSE), microtubuli associated protein Tau, S-100beta, amyloid-beta (Abeta(1-42)) and the 14-3-3 protein. Multiple studies have confirmed that CSF detection of 14-3-3 protein by Western blot was the best single biomarker for sCJD with an average sensitivity and specificity of 92%. Also, in genetic and iatrogenic CJD (iCJD) patients with an average disease duration of less than 1 year, 14-3-3 is the best differential biomarker. Unfortunately, the 14-3-3 protein has a lower sensitivity if the disease duration exceeds beyond 1 year in both sporadic CJD and other CJD types (vCJD, and specific genetic or iatrogenic CJD types).