Sensory disturbances in Creutzfeldt-Jakob disease.

BACKGROUND: Creutzfeldt-Jakob disease (CJD) is a fatal neurodegenerative disease characterized by rapidly progressive dementia, motor impairments, and psychiatric symptoms. Sensory disturbances were occasionally reported as well. The study aims to describe the sensory symptoms of the disease. METHODS: The CJD Israeli National Database was screened for patients who presented sensory symptoms throughout the disease course. Symptoms, characteristics, and distribution were reviewed and the demographic and clinical data (sex, etiologies of the disease, age of onset, disease duration, neurological exam finding, tau protein level, EEG and MRI findings) were compared with the demographics and clinical data of CJD without sensory symptoms. Then, the patients with sensory symptoms were divided into patients with symptom distribution consistent with peripheral nervous system (PNS) involvement and central nervous system (CNS) involvement. The demographics and clinical data of the 2 groups were compared. RESULTS: Eighty-four CJD patients with sensory symptoms and 645 CJD patients without sensory symptoms were included in the study. Sensory symptoms were more common in genetic E200K CJD patients (14.6% vs. 5.6% respectively, p = 0.0005) (chi-squared test). Numbness and neuropathic pain were the most common symptoms and distribution of symptoms of "stocking gloves" with decreased deep tendon reflexes suggesting peripheral neuropathy in 44% of the patients. In these patients, the classical EEG findings of Periodic Sharp Wave Complexes were less often found (58% vs. 22%, p = 0.02) (chi-squared test). CONCLUSIONS: Sensory symptoms are more common in E200K patients and often follow peripheral neuropathy distribution that suggests PNS involvement.

Genetic Creutzfeldt-Jakob disease in Turkish Jews-demographic and clinical features.

BACKGROUND: The largest cluster of genetic Creutzfeldt- Jakob Disease (CJD) exists in Libyan Jews carrying the E200K mutation in the PRNP gene. However, there is another cluster of genetic CJD with E200K mutation in families of Turkish-Jewish origin. AIMS: In this retrospective study, we aim to describe the demographic and clinical features of this population of patients. MATERIAL AND METHODS: The Israeli National CJD database was searched for demographic, clinical, imaging, and laboratory data of genetic CJD patients of Libyan and Turkish ancestry with the E200K mutation. The data of Libyan and Turkish patients were compared with notice similar or different demographic or clinical courses. RESULTS: Four hundred and twenty-three patients with CJD of Libyan (L) ancestry and 27 patients with CJD of Turkish (T) ancestry were identified. There were no significant differences in demographic and clinical data between the two populations (age of onset: T = 62 ± 8.8, L = 60 ± 9.7; age of death: T = 63 ± 8.6, L = 61 ± 9.7; and disease duration: T = 7.8 ± 8.4 months, L = 9.6 ± 13.6 months). Rapidly progressive dementia was the most common presentation in both groups, followed by pure cerebellar onset. The levels of tau protein in CSF did not differ between groups (T = 1290 ± 397.6 pg/ml, L = 1276 ± 594.2 pg/ml). MRI and EEG showed classical CJD features in most patients in both groups. DISCUSSION: The E200K mutation is the most common mutation among gCJD patients and was reported in different ethnical populations, suggesting several independent haplotypes of the mutation. The Turkish-Jew cluster, first described in this study, shares similar demographic and clinical features with the bigger cluster of Libyan-Jews CJD patients. CONCLUSION: E200K gCJD patients of Turkish ancestry share similar demographic and clinical features to patients of Libyan descent, suggesting a common origin of both populations.

Epidemiological and clinical characteristics of patients with late-onset Creutzfeldt-Jakob disease.

BACKGROUND: Creutzfeldt-Jacob disease (CJD) is a fatal neuro-degenerative disease, characterized by rapid and intense deterioration, mainly cognitive, leading to death. The typical onset of the disease is around the age of 67. PURPOSE: To characterize the demographic and clinical features of the population of CJD patients with late-onset disease. METHODS: In this retrospective study, the Israeli national database of prion diseases was screened for CJD patients with disease age of onset > 80 years between 1960 and 2016. Patient's demographic and clinical data were collected including sex, type of disease (sporadic/ genetic), clinical presentation, lab results including tau protein level, imaging, and EEG characteristics. Then, the clinical and demographic data of patients with late onset (> 80 years) (L) and patients with usual age of onset (< 80 years) (U) were compared. RESULTS: The study included 728 patients, 23 patients (3.3%) with late-onset disease (82.2.4±4 years, range 80-88) and 705 with usual disease onset (61.31 ± 9.47 years, range 34-80). Sporadic CJD was more common in the late-onset group (18/23 patients (78.2%) (L) vs. 256/705 patients (36.3%) (U)) (p = 0.0001, chi-square test). Classical EEG finding of periodic sharp wave activity were seen more often in the late-onset patients (55% (L) vs. 32.5% (U)) (p = 0.05, chi-square test). The rest of the demographic and clinical features were similar in both groups. CONCLUSION: Late- and usual-onset diseases are similar in most of demographic and clinical features suggesting a common disease type with normal distribution of age of onset.

Disease duration in E200K familial Creutzfeldt-Jakob disease is correlated with clinical, radiological, and laboratory variables.

Previous studies have suggested that disease duration in Creutzfeldt-Jakob disease (CJD) may be related to the radiological findings or cerebrospinal fluid (CSF) tau levels; however, it is not yet established whether clinical, radiological, and laboratory findings at diagnosis can predict survival or have a prognostic value. The aim of this study was to examine whether the disease duration is correlated with clinical, radiological, and laboratory variables. The study population consisted of consecutive familial CJD (fCJD) patients that were assessed within 1 week from the diagnosis including the CJD neurological scale (CJD-NS), Minimental Status Examination, Frontal Assessment Battery, NIH Stroke Scale, and the expanded disability status scale. In addition, a single MRI study was done and measurements of the extent of the cortical and subcortical involvement were performed. CSF was examined as part of the workout, and tau levels were determined. Sixty-nine fCJD patients were included in the study (43 males, mean age 59.3 ± 8.4, range 44-79 years). The mean disease duration was 7.3 ± 6.9 months (median 5.6 months, range 2-20 months). A significant correlation was found between the disease duration and the CJD-NS, the disease burden as reflected by the degree of cortical involvement by DWI, and the CSF tau levels. The findings of the current study reveal that several findings at disease onset including the disease severity, the cortical changes, and the tau levels are each individually correlated with disease duration and can be used by the clinician as a tool to predict the disease course and prognosis.

The association of quantitative EEG and MRI in Creutzfeldt-Jakob Disease.

INTRODUCTION: Previous studies showed concordance between the typical Periodic Sharp Wave Complex (PSWC) activity in EEG of Creutzfeldt-Jakob Disease (CJD) patients and the MRI findings, while the concordance with slow activity in EEG is less established. The aim of this study was to better characterize the association between MRI findings and EEG changes using quantitative EEG (qEEG) analysis. METHODS: The demographics, clinical features, and the MRI findings of 12 familial E200K patients with CJD were gathered. EEG test was done and reviewed for the typical PSWC and for the non-specific slow activity. A possible association between the MRI findings and the EEG activity was examined. Then, EEG was analyzed using qEEG tool, and the association between the qEEG finding and the MRI was examined. RESULTS: Twelve patients were included in the study (67% women). Cortical MRI lesions finding were seen in 6/12 (50%) of the patients, and deep gray mater lesions were seen in 8/12 patients (67%). EEG showed the classic PSWC in 6/12 (50%) of the patients where slow activity was seen in 10/12 (83%). Slow activity and cortical MRI findings were associated in only 2/6 (33%) where deep gray matter findings and the slow activity had concordance of 4/8 (50%). qEEG analysis improved this concordance between slow activity and cortical findings to 3/6 (50%) and with the deep gray matter findings to 5/8 (63%). CONCLUSIONS: Quantitative EEG analysis modesty but not significantly, improves the association of EEG slow activity in familial E200K CJD patients with MRI findings.

The impact of early versus late levodopa administration.

Long-term levodopa therapy in patients with Parkinson's disease (PD) is associated with motor complications including motor fluctuations (MF) and levodopa-induced dyskinesias (LID). The time to appearance of MF and LID is apparently related to both the timing and the duration of levodopa therapy, but is highly variable. We performed a retrospective analysis of all levodopa-treated PD patients to explore the effect of time from PD onset to levodopa initiation on time to MF or LID. We used a Cox multivariate regression model after stratifying patients into four quartiles, according to the time to levodopa initiation. Data from 170 PD patients (117 males, age at onset: 65.1 ± 11.6 years, time to levodopa treatment: 23.8 ± 28.4 months) was included in the analysis. Early levodopa administration was associated with a shorter time from diagnosis to both MF (p < 0.001) and LID (p = 0.001). The hazard ratio to develop MF and LID from the time of PD diagnosis was 2.48 (p < 0.001) and 2.71 (p = 0.002), respectively. In our population, we found that delaying levodopa administration was associated with a longer time to the appearance of motor complications after diagnosis. While disease duration is the most important determinant of the onset of motor complications, delaying levodopa could prolong the 'complication-free' period.

Clinical radiological correlation in E200K familial Creutzfeldt-Jakob disease.

The use of diffusion MRI improved the accuracy of diagnosis in Creutzfeldt-Jakob disease (CJD) and expanded our knowledge of the changes occurring in the brain during the disease. The aim of this study was to test whether in patients with E200K familial CJD (fCJD) the clinical severity correlates with the disease burden as reflected by the extent of cortical involvement in DWI MRI. Consecutive fCJD patients were examined by a neurologist who performed several tests including the CJD neurological scale (CJD-NS), MiniMental status examination (MMSE), Frontal Assessment Battery (FAB), NIH Stroke Scale (NIHSS), and the expanded disability status scale (EDSS). A simultaneously acquired MRI was analyzed by measuring the extent of cortical involvement in the DWI axial sequence. Correlations were tested for using Pearson test. Fifty-two fCJD patients (35 males, mean age 59.4 ± 5.7 years) were recruited to the study. Significant negative correlation was found between the extent of cortical involvement and the cognitive performance of the patients as reflected by their MMSE and FAB scores. In addition, a significant positive correlation was found between the MRI and the clinical disease severity scales CJD-NS and EDSS. The correlation between clinical scales of severity and cognitive dysfunction and the disease burden confirms the reliability of the CJD-NS scale. Further studies are warranted to examine whether MRI may serve not only for diagnosis but also as a biomarker for follow-up of disease progression and the efficacy of potential treatments.

Early pathology in sleep studies of patients with familial Creutzfeldt-Jakob disease.

In this study, we aimed to assess sleep function in patients with recent-onset familial Creutzfeldt-Jakob disease (fCJD). The largest cluster of fCJD patients is found in Jews of Libyan origin, linked to the prion protein gene (PRNP) E200K mutation. The high index of suspicion in these patients often leads to early diagnosis, with complaints of insomnia being a very common presenting symptom of the disease. The study included 10 fCJD patients diagnosed by clinical manifestations, magnetic resonance imaging (MRI) scan of the brain, elevated tau protein in the cerebrospinal fluid (CSF) and positive PRNP E200K mutation. Standard polysomnography was performed after a brief interview confirming the presence of sleep disturbances. All patients showed a pathological sleep pattern according to all scoring evaluation settings. The sleep stages were characterized by (i) disappearance of sleep spindles; (ii) outbursts of periodic sharp waves and shallowing of sleep consisting in increased Stage 2 and wake periods during the night, as well as decrease of slow-wave sleep and rapid eye movement (REM) sleep. Recordings of respiratory functions reported irregular breathing with central and obstructive apnea and hypopnea. The typical hypotonia occurring during the night and atonia during REM sleep were replaced by hyperactive sleep consisting of multiple jerks, movements and parasomnia (mainly talking) throughout the night. In conclusion, we report unique pathological sleep patterns in early fCJD associated with the E200K mutation. Specific respiratory disturbances and lack of atonia could possibly serve as new, early diagnostic tools in the disease.

Enhanced creative thinking under dopaminergic therapy in Parkinson disease.

OBJECTIVE: Creative thinking requires a combination of originality, flexibility, and usefulness. Several reports described enhanced artistic creativity in Parkinson disease (PD) patients treated with dopaminergic agents. We aimed to examine PD patients' ability to perform creativity tasks compared to healthy controls and to verify whether creativity is related to an impulse control disorder (ICD) as a complication of dopaminergic therapy. METHODS: Right-handed PD patients treated with dopamine agonists and/or levodopa, and age- and education- matched neurologically healthy controls were assessed using the Montreal Cognitive Assessment, semantic verbal fluency, Beck Depression Inventory, and Questionnaire for Impulsive-Compulsive Disorders in Parkinson Disease Rating Scale (QUIP-RS). Creativity assessment included Comprehension of Novel Metaphors (CNM), Remote Association Test, and Tel Aviv Creativity Test (TACT). Groups were compared using analyses of variance, t tests, and correlation analyses. RESULTS: Twenty-seven PD patients (age, mean ± standard deviation = 62 ± 7 years; education = 16 ± 3 years; disease duration = 5.8 ± 3.9 years) and 27 controls (age = 59 ± 9 years; education 17 ± 3 years) participated. PD patients performed significantly better than controls in divergent thinking tasks; specifically, the TACT-Visual for both fluency (33.48 ± 11.83 vs 25.59 ± 10.27, p = 0.034) and quality (15.78 ± 7.6 vs 11.19 ± 6.22, p = 0.025). Comprehension of Novel Metaphors was better in PD patients vs controls (0.71 ± 0.23 vs 0.55 ± 0.29, p = 0.04). QUIP-RS scores did not correlate with creativity measures. INTERPRETATION: PD patients treated with dopaminergic drugs demonstrated enhanced verbal and visual creativity as compared to neurologically healthy controls. This feature was unrelated to ICD. Dopaminergic agents might act through the reduction of latent inhibition, resulting in widening of the associative network and enriched divergent thinking.

Motor progression of Parkinson's disease with the leucine-rich repeat kinase 2 G2019S mutation.

INTRODUCTION: In this retrospective study, we compared motor disease progression in Ashkenazi-Jewish (AJ) Parkinson's disease (PD) patients carrying the LRRK2*G2019S mutation with that of noncarriers. METHODS: Consecutive PD patients were recruited between 2004 and 2011. Disease progression of carriers versus noncarriers was compared using survival analysis, where the end-point was the time from PD onset to reaching Hoehn and Yahr stage 3 (HY3). RESULTS: Overall, 405 AJ PD patients (males = 241[60%]) were genotyped, of whom 60 (males = 30) were LRRK2*G2019S mutation carriers. Time to HY3 did not differ significantly between mutation carriers and noncarriers (hazard ratio = 1.21, 95%CI = 0.83-1.77, P = 0.33). Age at PD onset was younger for carriers than for noncarriers (59.1 ± 9.8 vs. 63.2 ± 12.0 years, respectively; P = 0.005). In both groups, young age at onset was strongly associated with longer time to HY3, (P < 0.001). CONCLUSION: The LRRK2*G2019S mutation status has no discernible effect on the rate of motor disease progression in AJ PD patients.

Analysis of LMNB1 duplications in autosomal dominant leukodystrophy provides insights into duplication mechanisms and allele-specific expression.

Autosomal dominant leukodystrophy (ADLD) is an adult onset demyelinating disorder that is caused by duplications of the lamin B1 (LMNB1) gene. However, as only a few cases have been analyzed in detail, the mechanisms underlying LMNB1 duplications are unclear. We report the detailed molecular analysis of the largest collection of ADLD families studied, to date. We have identified the minimal duplicated region necessary for the disease, defined all the duplication junctions at the nucleotide level and identified the first inverted LMNB1 duplication. We have demonstrated that the duplications are not recurrent; patients with identical duplications share the same haplotype, likely inherited from a common founder and that the duplications originated from intrachromosomal events. The duplication junction sequences indicated that nonhomologous end joining or replication-based mechanisms such fork stalling and template switching or microhomology-mediated break induced repair are likely to be involved. LMNB1 expression was increased in patients' fibroblasts both at mRNA and protein levels and the three LMNB1 alleles in ADLD patients show equal expression, suggesting that regulatory regions are maintained within the rearranged segment. These results have allowed us to elucidate duplication mechanisms and provide insights into allele-specific LMNB1 expression levels.

The epidemiological and clinical characteristics of patients with young-onset genetic Creutzfeldt-Jakob disease.

OBJECTIVES: The onset of Creutzfeldt-Jakob disease (CJD) is usually around the age of 60, but younger patients have been described as well. Our study characterizes the demographic and clinical features of young-onset CJD patients. METHODS: The CJD Israeli National Database was reviewed, and the patients were divided into groups of young (<40-year-old) (Y|) and older disease onset (>40-year-old) (O). Each group was further divided into sporadic (sCJD) and genetic (gCJD) patients. Clinical and demographic parameters were compared between the groups. RESULTS: The study included 731 patients (Y- 18 patients, O- 713 patients). MRI showed classical features more often in the older population (O-76.9%, Y-36%, p = 0.006). Rapidly progressive dementia as a presenting feature was more common in the older group (O = 58%, Y = 27.7%, p = 0.019) whereas cerebellar onset (gait instability, dysarthria) was more common in the younger group (O = 6.7%, Y = 27.7%, p = 0.036)). Among gCJD patients, rapidly progressive dementia was commonly seen in older patients (O = 54%, Y = 21% p = 0.008) whereas cerebellar symptoms were seen in young patients (O = 7%, Y = 30% p = 0.01) Typical MRI findings were seen in 37% of young people compared to 87% of older patients (p = 0.002). No significant differences were between young and older patients in the sCJD group. CONCLUSION: Young-onset gCJD patients have unique disease features including less typical brain MRI changes, a lower prevalence of dementia, and a higher prevalence of cerebellar signs at disease onset.

The frontal assessment battery as a tool for evaluation of frontal lobe dysfunction in patients with Parkinson disease.

BACKGROUND: Frontal-type cognitive deficits are common in patients with Parkinson disease (PD). The Frontal Assessment Battery (FAB) was developed to assess frontal lobe functions. However, many studies found that it also correlated with a variety of other general neuropsychological tests. OBJECTIVES: To evaluate whether the FAB has an added value over the Mini-Mental State Examination (MMSE) and other bedside neuropsychological tests in reflecting cognitive deficits in patients with PD. METHODS: Seventy-two consecutive patients with PD underwent cognitive assessment including the FAB, the MMSE, and a variety of other neuropsychological tests. Correlations were examined using the Spearman's r. RESULTS: Highly significant correlations were found between the total FAB score and tests of attention, executive functions, and memory. To evaluate the contribution of the FAB beyond that of the MMSE, partial correlation was used. Analyses revealed that the FAB still correlated with most of the tests. Dividing the patients according to the median MMSE score revealed that the high correlation between the FAB and the MMSE was preserved in the low MMSE group, while in the high MMSE group the correlation was relatively low. In the high MMSE group, the FAB correlated with 11 tests compared to the MMSE that correlated with one (P < .001), while in the low MMSE group the number of correlations was 13 versus 7, respectively (P = .05). CONCLUSIONS: In our sample of patients with PD, the FAB correlated with dysfunction in a variety of cognitive domains including attention, memory, and executive functions. The FAB has an added value over the MMSE, particularly among nondemented patients, an advantage that can be used in clinical practice.

Characterization of movement disorders in patients with familial Creutzfeldt-Jakob disease carrying the E200K mutation.

BACKGROUND: While myoclonus and ataxia are considered common in patients with familial Creutzfeld-Jakob disease (fCJD), other movement disorders are less prevalent. OBJECTIVES: To systemically evaluate the frequency of extrapyramidal signs and movement disorders in patients with fCJD. METHODS: A detailed neurological examination, with special emphasis on movement disorders and extrapyramidal signs, was conducted in 43 consecutive symptomatic CJD patients (26 males and 17 females; mean age 58.7 +/- 8.9 yrs, range 43-77 years) carrying the E200K mutation in the PRNPgene. RESULTS: Limb or gait ataxia was noted in 38 patients (88%) (37 patients, 86%, had ataxia at presentation). Myoclonus was evident in 25/43 patients (58%) (21 patients, 49%, at presentation). In 95% of the patients (41/43) (37/43, 86% at presentation) at least one extrapyramidal sign throughout the disease course was noted, the most prevalent being rigidity (28/43, 65% of the patients; and 22/43, 51% at presentation), followed by the glabellar sign (24/43, 56% of the patients; and 22/43, 51% at presentation), bradykinesia (19/43, 44%; and 15/43, 35% at presentation), dystonia (15/43, 35%; 12/43, 28% at presentation) and tremor (13/43, 30%; 12/43, 28% at presentation). CONCLUSIONS: In this unique population of fCJD patients, myoclonus was less prevalent than previously reported while other extrapyramidal signs were common and occurred at a relatively early stage of the disease. The high prevalence of movement disorders can be added to other phenomena characteristic of this familial disorder among Libyan lews. Whether this is attributable to the E200K mutation itself or to some other mechanism has still to be elucidated.

Identification of an early-stage Parkinson's disease neuromarker using event-related potentials, brain network analytics and machine-learning.

OBJECTIVE: The purpose of this study is to explore the possibility of developing a biomarker that can discriminate early-stage Parkinson's disease from healthy brain function using electroencephalography (EEG) event-related potentials (ERPs) in combination with Brain Network Analytics (BNA) technology and machine learning (ML) algorithms. BACKGROUND: Currently, diagnosis of PD depends mainly on motor signs and symptoms. However, there is need for biomarkers that detect PD at an earlier stage to allow intervention and monitoring of potential disease-modifying therapies. Cognitive impairment may appear before motor symptoms, and it tends to worsen with disease progression. While ERPs obtained during cognitive tasks performance represent processing stages of cognitive brain functions, they have not yet been established as sensitive or specific markers for early-stage PD. METHODS: Nineteen PD patients (disease duration of ≤2 years) and 30 healthy controls (HC) underwent EEG recording while performing visual Go/No-Go and auditory Oddball cognitive tasks. ERPs were analyzed by the BNA technology, and a ML algorithm identified a combination of features that distinguish early PD from HC. We used a logistic regression classifier with a 10-fold cross-validation. RESULTS: The ML algorithm identified a neuromarker comprising 15 BNA features that discriminated early PD patients from HC. The area-under-the-curve of the receiver-operating characteristic curve was 0.79. Sensitivity and specificity were 0.74 and 0.73, respectively. The five most important features could be classified into three cognitive functions: early sensory processing (P50 amplitude, N100 latency), filtering of information (P200 amplitude and topographic similarity), and response-locked activity (P-200 topographic similarity preceding the motor response in the visual Go/No-Go task). CONCLUSIONS: This pilot study found that BNA can identify patients with early PD using an advanced analysis of ERPs. These results need to be validated in a larger PD patient sample and assessed for people with premotor phase of PD.

Genomic duplications mediate overexpression of lamin B1 in adult-onset autosomal dominant leukodystrophy (ADLD) with autonomic symptoms.

Adult-onset autosomal dominant leukodystrophy (ADLD) with autonomic symptoms features micturition urgency, constipation, erectile dysfunction, and orthostatic hypotension, usually followed by pyramidal signs and ataxia. Peripheral nerve conduction is normal. The disease is often mistaken for multiple sclerosis in the initial phase. There is a characteristic pattern of white matter changes in the brain and spinal cord on magnetic resonance imaging (MRI), mild atrophy of the brain, and a more marked atrophy of the spinal cord. ADLD is associated with duplications of the lamin B1 (LMNB1) gene but the mechanism by which the rearrangement conveys the phenotype is not fully defined. We analyzed four unrelated families segregating ADLD with autonomic symptoms for duplications of the LMNB1 gene. A single nucleotide polymorphism (SNP) array analysis revealed novel duplications spanning the entire LMNB1 gene in probands from each of the four families. We then analyzed the expression of lamin B1 in peripheral leukocytes by Western blot analysis in five patients from two available families. The protein levels of lamin B1 were found significantly increased. These results indicate that the ADLD phenotype associated with LMNB1 duplications is mediated by increased levels of the lamin B1 protein. Furthermore, we show that a molecular diagnosis for ADLD with autonomic symptoms can be obtained by a direct analysis of lamin B1 in peripheral leukocytes.

Phenotype of the 202 adenine deletion in the parkin gene: 40 years of follow-up.

BACKGROUND: We describe the four decades follow-up of 14 parkin patients belonging to two large eight-generation-long in-bred Muslim-Arab kindreds. RESULTS: All patients had a single base-pair of adenine deletion at nucleotide 202 of exon 2 (202A) of the parkin gene (all homozygous, one heterozygous). Parkinson's disease onset age was 17-68 years. Special features were intractable axial symptoms (low back pain, scoliosis, camptocormia, antecollis), postural tremor, and preserved cognition. CONCLUSIONS: The 202A deletion of the parkin gene causes early-onset Parkinson's disease with marked levodopa/STN-DBS-resistant axial features. Postural tremor and preserved cognition, even after 40 years of disease, were also evident.

Is C-reactive protein level a marker of advanced motor and neuropsychiatric complications in Parkinson's disease?

C-reactive protein (CRP) is a plasma protein involved in inflammation. While its levels have been associated with stroke, cognitive impairment and depression, the association with clinical characteristics of Parkinson's disease (PD) is unknown. A total of 73 consecutive patients with PD (46 males, age 68.8 ± 11.5 years) were evaluated regarding motor as well as cognitive and psychiatric features of PD. Plasma CRP levels were determined and tests for associations with disease parameters were performed. The average level of CRP was 3.9 ± 4.1 µmol/L, and 45.2% of the patients (n = 33) had a level above 3.0 µmol/L. Patients in the high CRP group tended to be older (71.4 ± 9.2 vs. 66.7 ± 12.9 years; p = 0.08) and coronary artery disease (CAD) was more common (36 vs. 10%, p < 0.05) in the high CRP group, but no differences were found between the groups regarding gender, disease duration, levodopa dose, motor scores or most of the neuropsychiatric complications such as severity of depression, psychosis, dementia, cognitive decline or frontal lobe dysfunction. Reported depression (at present or in the past) was more common in the high CRP group (54.5 vs. 25%, p = 0.01). CRP levels in patients with PD are associated with a higher prevalence of CAD, but are not associated with PD duration or severity, or with neuropsychiatric complications other than reported depression.

Spatial distribution of abnormal EEG activity in Creutzfeldt-Jakob disease.

OBJECTIVES: Electroencephalogram (EEG) pattern in Creutzfeldt-Jakob disease (CJD) is characterized by diffuse abnormal activity, although lateralization to one hemisphere has been described in the first stages of the disease. This study aimed to determine whether abnormal EEG activity predominantly occurs in anterior versus posterior brain regions. METHODS: As part of a prospective study, the demographics, clinical features and MRI findings of genetic E200K CJD patients were collected. EEG was performed and the recordings reviewed for the typical periodic sharp wave complex (PSWC) and non-specific slow activity. Data were analyzed using the qEEG tool, and the activity in anterior and posterior regions of the brain compared. RESULTS: Eleven genetic E200K CJD patients were included in the study (67% women). The average age was 59.1 ±â€¯8.4 SD years and the average disease duration was 2.4 ±â€¯2.1 months. EEG showed the classic PSWC pattern in 5/11 (45%) of the patients, and slow activity was seen in 9/11 (82%). EEG was normal in 2 patients. PSWC activity was diffuse in 2/5 patients and unilateral in 3/5 patients; slow activity was diffuse in 9 patients. Quantitative analysis of PSWC and slow activity showed no significant difference between anterior and posterior distribution. CONCLUSION: The abnormal EEG activity in CJD is diffuse with no clear spatial predominance in anterior or posterior brain regions.

Thalamo-striatal diffusion reductions precede disease onset in prion mutation carriers.

Human prion diseases present substantial scientific and public health challenges. They are unique in being sporadic, infectious and inherited, and their pathogen is distinct from all other pathogens in lacking nucleic acids. Despite progress in understanding the molecular structure of prions, their initial cerebral pathophysiology and the loci of cerebral injury are poorly understood. As part of a large prospective study, we analysed early diffusion MRI scans of 14 patients with the E200K genetic form of Creutzfeldt-Jakob Disease, 20 healthy carriers of this mutation that causes the disease and 20 controls without the mutation from the same families. Cerebral diffusion was quantified by the Apparent Diffusion Coefficient, and analysed by voxel-wise statistical parametric mapping technique. Compared to the mutation-negative controls, diffusion was significantly reduced in a thalamic-striatal network, comprising the putamen and mediodorsal, ventrolateral and pulvinar thalamic nuclei, in both the patients and the healthy mutation carriers. With disease onset, these diffusion reductions intensified, but did not spread to other areas. The caudate nucleus was reduced only after symptomatic onset. These findings indicate that cerebral diffusion reductions can be detected early in the course of Creutzfeldt-Jakob Disease, and years before symptomatic onset in mutation carriers, in a distinct subcortical network. We suggest that this network is centrally involved in the pathogenesis of Creutzfeldt-Jakob Disease, and its anatomical connections are sufficient to account for the common symptoms of this disease. Further, we suggest that the abnormalities in healthy mutation-carrying subjects may reflect the accumulation of abnormal prion protein and/or associated vacuolation at this time, temporally close to disease onset.