Motor cortical excitability and pre-supplementary motor area neurochemistry in healthy adults with substantia nigra hyperechogenicity.

Substantia nigra (SN) hyperechogenicity, viewed with transcranial ultrasound, is a risk marker for Parkinson's disease. We hypothesized that SN hyperechogenicity in healthy adults aged 50-70 years is associated with reduced short-interval intracortical inhibition in primary motor cortex, and that the reduced intracortical inhibition is associated with neurochemical markers of activity in the pre-supplementary motor area (pre-SMA). Short-interval intracortical inhibition and intracortical facilitation in primary motor cortex was assessed with paired-pulse transcranial magnetic stimulation in 23 healthy adults with normal (n = 14; 61 ± 7 yrs) or abnormally enlarged (hyperechogenic; n = 9; 60 ± 6 yrs) area of SN echogenicity. Thirteen of these participants (7 SN- and 6 SN+) also underwent brain magnetic resonance spectroscopy to investigate pre-SMA neurochemistry. There was no relationship between area of SN echogenicity and short-interval intracortical inhibition in the ipsilateral primary motor cortex. There was a significant positive relationship, however, between area of echogenicity in the right SN and the magnitude of intracortical facilitation in the right (ipsilateral) primary motor cortex (p = .005; multivariate regression), evidenced by the amplitude of the conditioned motor evoked potential (MEP) at the 10-12 ms interstimulus interval. This relationship was not present on the left side. Pre-SMA glutamate did not predict primary motor cortex inhibition or facilitation. The results suggest that SN hyperechogenicity in healthy older adults may be associated with changes in excitability of motor cortical circuitry. The results advance understanding of brain changes in healthy older adults at risk of Parkinson's disease.

Neurologic manifestations of COVID-19 in critically ill patients: results of the prospective multicenter registry PANDEMIC.

BACKGROUND: Neurologic manifestations are increasingly reported in patients with coronavirus disease 2019 (COVID-19). Yet, data on prevalence, predictors and relevance for outcome of neurological manifestations in patients requiring intensive care are scarce. We aimed to characterize prevalence, risk factors and impact on outcome of neurologic manifestations in critically ill COVID-19 patients. METHODS: In the prospective, multicenter, observational registry study PANDEMIC (Pooled Analysis of Neurologic DisordErs Manifesting in Intensive care of COVID-19), we enrolled COVID-19 patients with neurologic manifestations admitted to 19 German intensive care units (ICU) between April 2020 and September 2021. We performed descriptive and explorative statistical analyses. Multivariable models were used to investigate factors associated with disorder categories and their underlying diagnoses as well as to identify predictors of outcome. RESULTS: Of the 392 patients included in the analysis, 70.7% (277/392) were male and the mean age was 65.3 (SD ± 3.1) years. During the study period, a total of 2681 patients with COVID-19 were treated at the ICUs of 15 participating centers. New neurologic disorders were identified in 350 patients, reported by these centers, suggesting a prevalence of COVID-19-associated neurologic disorders of 12.7% among COVID-19 ICU patients. Encephalopathy (46.2%; 181/392), cerebrovascular (41.0%; 161/392) and neuromuscular disorders (20.4%; 80/392) were the most frequent categories identified. Out of 35 cerebrospinal fluid analyses with reverse transcriptase PCR for SARS-COV-2, only 3 were positive. In-hospital mortality was 36.0% (140/389), and functional outcome (mRS 3 to 5) of surviving patients was poor at hospital discharge in 70.9% (161/227). Intracerebral hemorrhage (OR 6.2, 95% CI 2.5-14.9, p < 0.001) and acute ischemic stroke (OR 3.9, 95% CI 1.9-8.2, p < 0.001) were the strongest predictors of poor outcome among the included patients. CONCLUSIONS: Based on this well-characterized COVID-19 ICU cohort, that comprised 12.7% of all severe ill COVID-19 patients, neurologic manifestations increase mortality and morbidity. Since no reliable evidence of direct viral affection of the nervous system by COVID-19 could be found, these neurologic manifestations may for a great part be indirect para- or postinfectious sequelae of the infection or severe critical illness. Neurologic ICU complications should be actively searched for and treated.

COVID-19 and Intracranial Hemorrhage: A Multicenter Case Series, Systematic Review and Pooled Analysis.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) profoundly impacts hemostasis and microvasculature. In the light of the dilemma between thromboembolic and hemorrhagic complications, in the present paper, we systematically investigate the prevalence, mortality, radiological subtypes, and clinical characteristics of intracranial hemorrhage (ICH) in coronavirus disease (COVID-19) patients. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we performed a systematic review of the literature by screening the PubMed database and included patients diagnosed with COVID-19 and concomitant ICH. We performed a pooled analysis, including a prospectively collected cohort of critically ill COVID-19 patients with ICH, as part of the PANDEMIC registry (Pooled Analysis of Neurologic Disorders Manifesting in Intensive Care of COVID-19). RESULTS: Our literature review revealed a total of 217 citations. After the selection process, 79 studies and a total of 477 patients were included. The median age was 58.8 years. A total of 23.3% of patients experienced the critical stage of COVID-19, 62.7% of patients were on anticoagulation and 27.5% of the patients received ECMO. The prevalence of ICH was at 0.85% and the mortality at 52.18%, respectively. CONCLUSION: ICH in COVID-19 patients is rare, but it has a very poor prognosis. Different subtypes of ICH seen in COVID-19, support the assumption of heterogeneous and multifaceted pathomechanisms contributing to ICH in COVID-19. Further clinical and pathophysiological investigations are warranted to resolve the conflict between thromboembolic and hemorrhagic complications in the future.

Automated Pupillometry for Assessment of Treatment Success in Nonconvulsive Status Epilepticus.

BACKGROUND: Altered pupillary function may reflect nonconvulsive status epilepticus (NCSE). Neurological pupil index (NPi) assessed by automated pupillometry is a surrogate marker of global pupillary function. We aimed to assess NPi changes in relation to NCSE treatment response. METHODS: In this prospective observational study, serial automated pupillometry was performed in 68 NCSE episodes. In accordance with local standards, patients were treated with clonazepam (1-2 mg), levetiracetam (40 mg/kg), and lacosamide (5 mg/kg) in a stepwise approach under continuous electroencephalography monitoring until NCSE was terminated. Patients with refractory NCSE received individualized regimens. NPi was assessed bilaterally before and after each treatment step. For statistical analysis, the lower NPi of both sides (minNPi) was used. Nonparametric testing for matched samples and Cohen's d to estimate effect size were performed. Principal component analysis was applied to assess the contribution of baseline minNPi, age, sex, and NCSE duration to treatment outcome. RESULTS: In 97.1% of 68 episodes, NCSE could be terminated; in 16.2%, NCSE was refractory. In 85.3% of episodes, an abnormal baseline minNPi ≤ 4.0 was obtained. After NCSE termination, minNPi increased significantly (p < 0.001). Cohen's d showed a strong effect size of 1.24 (95% confidence interval 0.88-1.61). Baseline minNPi was higher in clonazepam nonresponders vs. responders (p = 0.008), minNPi increased in responders (p < 0.001) but not in nonresponders. NCSE refractivity was associated with normal baseline minNPi (principal component analysis, component 1, 32.6% of variance, r = 0.78), male sex, and longer NCSE duration (component 2, 27.1% of variance, r = 0.62 and r = 0.78, respectively). CONCLUSIONS: Automated pupillometry may be a helpful noninvasive neuromonitoring tool for the assessment of patients with NCSE and response to treatment.

CSF shunt valve occlusion-does CSF protein and cell count matter?

BACKGROUND: Shunt obstruction is a common cause of shunt failure in the treatment of hydrocephalus. Valve occlusion is traditionally believed to originate from elevated CSF protein or cellular components, although detailed evidence is scarce and contradictory. Therefore, this study aimed to examine CSF protein and cell count as risk factors for valve obstruction. METHODS: We retrospectively examined 274 patients who underwent shunt placement for hydrocephalus between 2009 and 2018 and had at least 1 year follow-up. Age, aetiology of hydrocephalus, valve type, occurrence of revision, reason for revision and CSF protein and cell count at the time of shunt insertion and revision surgery were analysed. RESULTS: Thirty-two of 274 patients (11.7%) required revision surgery due to valve occlusion. Mean time to revision was 143 days. CSF white blood cell (WBC) count but not protein was associated with valve occlusion overall. Of all obstructed valve patients, 25% showed CSF protein level within the normal range, whereas 13.6% of the patients overall showed greatly elevated CSF protein level without evidence of valve obstruction. Persistently elevated CSF protein level at the time of shunt revision was significantly associated with valve obstruction within 90 days of initial insertion (early occlusion). Children with congenital malformations and post-haemorrhagic patients were significantly overrepresented in the occlusion group, particularly in the early occlusion group. CONCLUSION: Pathological CSF values such as WBC count and persistently elevated protein level serves as a risk factor for early valve obstruction. Late obstruction occurs independent of normal CSF values. Infants are particularly prone to early and late valve obstructions. CSF protein level at shunt insertion is not predictive of valve occlusion.

Recognition and treatment of status epilepticus in the prehospital setting.

PURPOSE: We performed this retrospective data bank analysis to evaluate the management of status epilepticus (SE) in the prehospital setting and the possible association of treatment delay or insufficient treatment approach with outcome. METHOD: We evaluated all treatment episodes of a prehospital SE according to our hospital record system between January 1st 2014 and December 31st 2018. Classification according to the ILAE classification of 2015, Status Epilepticus Severity Score (STESS), Charlson Comorbidity Index (CCI) at admission and the Modified Rankin Scale (mRS) at discharge or in hospital death were recorded or calculated. Statistical analysis was performed with the Mann-Withney-U test, the Chi-Square test and corrections of Yates and Bonferroni-Holmes where appropriate. RESULTS: There were 331 treatment episodes in 282 patients with a fatality rate of 7.6 %. Median age at treatment was 72 years. Patients who died were significantly older and had a higher STESS and CCI than patients who survived. SE was recognised in the prehospital setting in only 56.8 % of treatment episodes. Patients in treatment episodes with recognized SE were significantly younger than the others. Status epilepticus was more often recognized, when epilepsy was known. Overall in 48 % of treatment episodes with another SE type than generalized convulsive SE the diagnosis was missed. CCI was significantly higher in the episodes without recognized SE. Patients were more often discharged from hospital with a new deficit, when the SE was not recognized in the prehospital setting. In treatment episodes with initiation of a benzodiazepine (BZD) the patients were more likely to be discharged without a new deficit than others. After excluding cases with insufficient documentation of treatment steps 273 treatment episodes remained. In 178 of these treatment episodes epilepsy was known before, but in only 11.2 % of them a rescue medication was given by bystanders. In only 6.7 % of treatment episodes of SE in patients with known epilepsy a BZD was given in an appropriate way by bystanders. In nearly all treatment episodes with lorazepam (88.9 %) or midazolam (97.8 %) the dosage was below the recommended level. CONCLUSIONS: Missing the SE in the prehospital setting was frequent and associated with a higher risk of developing a new neurological deficit. Treatment with BZD was associated with a lower risk of developing a new neurological deficit, but was underdosed in the vast majority of situations.

Quantitative Infrared Pupillometry in Nonconvulsive Status Epilepticus.

BACKGROUND: Nonconvulsive status epilepticus (NCSE) is a frequent disorder in neurocritical care and diagnosing it can be challenging. NCSE patients often show altered pupil function, but nature and extent may vary. Infrared pupillometry allows detection of subtle changes of pupil function. The neurological pupil index (NPi) is considered a surrogate marker of global pupil function which is supposed to be independent of absolute parameters such as the pupil diameter. OBJECTIVE: Cross-sectional observational study to assess whether NPi is altered in NCSE. METHODS: 128 consecutive adult emergency patients who had experienced a suspected seizure, have not reached their prior functional level regarding level of consciousness, mental status or focal deficits, had no obvious clinical signs of status epilepticus and had an EEG indication as determined by the treating clinician for exclusion of NCSE were examined by routine EEG and pupillometry. Exclusion criteria were ocular comorbidity (n = 21) and poor EEG quality (n = 4). Pupillometry was performed once directly before the beginning of EEG recording. NCSE diagnosis (no NCSE, possible NCSE and confirmed NCSE) was established according to Salzburg consensus criteria blinded to pupillometry results. Group comparison was performed for right NPi, left NPi, lowest NPi of both sides (minNPi) and the absolute difference of both sides (diffNPi) applying non-parametric testing. In post-hoc analysis, receiver operating characteristics (ROC) of NCSE diagnosis (combined confirmed NCSE and possible NCSE) were performed for minNPi and diffNPi. RESULTS: From 103 patients included in the final analysis, 5 (4.9%) had confirmed NCSE, 7 (6.8%) had possible NCSE. Right NPi (p = 0.002), left NPi (p < 0.001) and minNPi (p < 0.001) were significantly lower in "confirmed NCSE" and "possible NCSE" compared to "no NCSE"; diffNPi was significantly higher in "confirmed NCSE" and "possible NCSE" compared to "no NCSE" (p < 0.001). There was no significant difference of minNPi and diffNPi between "confirmed NCSE" and "possible NCSE". ROC analysis showed an optimal cut-off of minNPi for NCSE diagnosis of 4.0 (AUC = 0.93, 95% CI 0.86-0.99). Optimal ROC analysis cut-off of diffNPi for NCSE diagnosis was 0.2 (AUC = 0.89, 95% CI 0.80-0.99). CONCLUSIONS: NPi was significantly reduced and the difference between left and right NPi was significantly higher in confirmed NCSE. An NPi < 4.0 on either side as well as an NPi difference of both sides > 0.2 may be potential indicators of NCSE. Infrared pupillometry may be a helpful diagnostic tool in the assessment of NCSE and should be studied further in larger populations.

[Levetiracetam for treatment of status epilepticus - an update]. / Levetiracetam in der Behandlung des Status epilepticus ­ ein update.

Since 2004 several reports on the treatment of status epilepticus with levetiracetam have been published. In this review, the results of a PubMed-based search of publications December 12, 2011 - July 6, 2018 are summarized and compared to those of earlier publications. In total, 28 treatment episodes in case reports, each on one or two cases of treatment episodes, and 412 treatment episodes in case series and prospective studies were analyzed. Case series and prospective studies reported an average success rate for termination of status probably of 55,0 %-59,4 %. Since preclinical data suggest a delayed effect of levetiracetam, its use in the treatment of generalized convulsive status epilepticus appears still questionable. A loading dose of 30 mg / kg seems to be reasonable.

Association of Plasma Aß40 Peptides, But Not Aß42, with Coronary Artery Disease and Diabetes Mellitus.

BACKGROUND/OBJECTIVE: Plasma levels of amyloid-beta (Aß) 1-40 peptide have been proposed to be associated with cardiovascular mortality in patients with coronary artery disease (CAD). Therefore, we aimed to investigate the association of plasma Aß levels with CAD, cardiovascular risk factors (CVRF), and APOE genotype in non-demented elderly individuals. METHODS: Plasma Aß1 - 40 and Aß1 - 42 levels of 526 individuals (mean age of 63.0±7.3 years) were quantified with the INNO-BIA plasma Aß forms assay based on multiplextrademark technique. APOE genotype was determined with an established protocol. Presence of CAD and CVRFs were ascertained using a questionnaire and/or medical records. RESULTS: Plasma Aß1 - 40 levels were significantly higher in individuals with CAD (p = 0.043) and, independently, in individuals with diabetes mellitus (DM) type 2 (p = 0.001) while accounting for age- and gender-effects. Plasma Aß1 - 42 levels were higher in APOEɛ4 carriers (p = 0.004), but were neither relevantly associated with CAD nor with any CVRF. Plasma Aß1 - 40 showed no association with APOE genotype. DISCUSSION: Our findings argue for an association of circulating plasma Aß1 - 40 peptides with incident CAD and DM. Further investigations are needed to entangle the role of Aß1 - 40 role in the pathophysiology of cardiovascular disease independent of its known role in Alzheimer's disease.

Gait velocity and step length at baseline predict outcome of Nordic walking training in patients with Parkinson's disease.

BACKGROUND: The impact of Nordic walking (NW) in Parkinson's disease (PD) has been investigated in several studies but results are inconsistent. This may be due to different cohorts studied and the heterogeneity of their PD symptoms which impact the outcome of NW. This study aimed at determining predictive factors for a positive effect of NW on PD. METHODOLOGY AND PRINCIPAL FINDINGS: Primary outcome was to define the baseline disease-associated and demographic parameters that distinguish patients who demonstrate improvement in the Unified PD rating scale (UPDRS) motor part following NW training ("U+") from those patients with no improvement after the same intervention ("U-"). The potentially predictive parameters were: age, age at onset, disease duration, gait velocity, step length, daily step number, UPDRS-motor part, Berg-Balance-Scale, Parkinson-Neuropsychometric-Dementia-Assessment, verbal-fluency-test and Becks-Depression-Inventory-II. Twenty-two PD patients (H&Y stage 2-2.5) performed twelve weeks of NW training. Eighteen patients were included in the final analysis. Overall, the UPDRS motor part did not improve significantly; however, eight patients had an improvement in the UPDRS motor part from baseline to end of study (U+). When comparing the potentially predictive factors of the U+ cohort with those ten patients who did not improve (U-), there was a notable difference in gait velocity and step length, and showed a significant correlation with an improvement in the UDPRS motor part scores. CONCLUSION: Gait velocity and step length can predict the outcome of NW training as determined by the UPDRS motor part, indicating that PD patients with only slightly impaired gait performance benefit most.

Clinical characteristics related to worsening of motor function assessed by the Unified Parkinson's Disease Rating Scale in the elderly population.

There is evidence that nigrostriatal pathology may at least partly underlie mild Parkinsonian signs. We evaluated whether an increase in the Unified Parkinson's Disease Rating Scale part III (UPDRS-III) could be predicted by the presence of risk and prodromal markers for neurodegenerative diseases in elderly individuals without those diseases. Therefore, we analyzed the UPDRS-III score and various risk and prodromal markers known to antecede neurodegenerative diseases in a population-based cohort comprising 807 individuals free of neurodegenerative diseases at baseline. After 5 years, eight persons (1.0 %) were diagnosed with Parkinson's Disease (PD). Of those, seven (87.5 %) had motor worsening ≥3 points on the UPDRS-III from baseline to follow-up, one had two points increase. Of the 788 people without PD, 568 (72.1 %) showed no increase in the UPDRS-III scale, 220 (27.9 %) had ≥1 point increase and out of these 104 (13.2 %) had an increase of ≥3 points in the UPDRS-III score after 5 years. We identified an age >60 years (relative risk, RR = 1.7; confidence interval, CI 1.3-2.1) and the occurrence of ≥2 risk factors (RR = 1.5; CI 1.2-1.9) as possible predictors of motor progression. After 5 years, individuals with an increase in the UPDRS-III score had more often a one-sided reduced arm swing (p < 0.001) and identified less odors in the Sniffin' sticks test (p < 0.041) than persons with stable motor performance. Our data support the assumption that progression of Parkinsonian signs assessed by the UPDRS-III parallels the development of prodromal markers for neurodegenerative diseases in the elderly population.

Does prone positioning increase intracranial pressure? A retrospective analysis of patients with acute brain injury and acute respiratory failure.

PURPOSE: The objective of our trial was to obtain more comprehensive data on the risks and benefits of kinetic therapy in intensive care patients with intracerebral pathology. METHODS: Standardized data of prone positioning in our NeuroIntensive Care Unit were collected from 2007 onward. A post hoc analysis of all available data was undertaken, with special consideration given to values of intracranial pressure (ICP), cerebral perfusion pressure (CPP) and oxygenation in correlation to prone (PP), or supine positioning (SP) of patients. Cases were considered eligible if kinetic therapy and ICP were documented. Prone positioning was performed in a 135° position for 8 h per treatment unit. RESULTS: A total of 115 patients treated with prone positioning from 2007 to 2013 were identified in our medical records. Of these, 29 patients received ICP monitoring. Overall, 119 treatment units of prone positioning with a mean duration of 2.5 days per patient were performed. The mean baseline ICP in SP was 9.5 ± 5.9 mmHg and was increased significantly during PP (p < 0.0001). There was no significant difference between CPP in SP (82 ± 14.5 mmHg) compared to PP (p > 0.05). ICP values >20 mmHg occurred more often during PP than SP (p < 0.0001) and were associated with significantly more episodes of decreased CPP <70 mmHg (p < 0.0022). The mean paO(2)/FiO(2) ratio (P/F ratio) was increased significantly in prone positioning of patients (p < 0.0001). CONCLUSIONS: The analyzed data allow a more precise understanding of changes in ICP and oxygenation during prone positioning in patients with acute brain injury and almost normal baseline ICP. Our study shows a moderate, yet significant elevation of ICP during prone positioning. However, the achieved increase of oxygenation by far exceeded the changes in ICP. It is evident that continuous monitoring of cerebral pressure is required in this patient group.

Hand function is impaired in healthy older adults at risk of Parkinson's disease.

Abnormal substantia nigra morphology in healthy individuals, viewed with transcranial ultrasound, is a significant risk factor for Parkinson's disease. However, little is known about the functional consequences of this abnormality (termed 'hyperechogenicity') on movement. The aim of the current study was to investigate hand function in healthy older adults with (SN+) and without (SN-) substantia nigra hyperechogenicity during object manipulation. We hypothesised that SN+ subjects would exhibit increased grip force and a slower rate of force application compared to SN- subjects. Twenty-six healthy older adults (8 SN+ aged 58 ± 8 years, 18 SN- aged 57 ± 6 years) were asked to grip and lift a light-weight object with the dominant hand. Horizontal grip force, vertical lift force, acceleration, and first dorsal interosseus EMG were recorded during three trials. During the first trial, SN+ subjects exhibited a longer period between grip onset and lift onset (i.e. preload duration; 0.27 ± 0.25 s) than SN- subjects (0.13 ± 0.08 s; P = 0.046). They also exerted a greater downward force prior to lift off (-0.54 ± 0.42 N vs. -0.21 ± 0.12 N; P = 0.005) and used a greater grip force to lift the object (19.5 ± 7.0 N vs. 14.0 ± 4.3 N; P = 0.022) than SN- subjects. No between group differences were observed in subsequent trials. SN+ subjects exhibit impaired planning for manipulation of new objects. SN+ individuals over-estimate the grip force required, despite a longer contact period prior to lifting the object. The pattern of impairment observed in SN+ subjects shares similarities with de novo Parkinson's disease patients.

Risk factors and prodromal markers and the development of Parkinson's disease.

Identification of risk factors and prodromal markers for Parkinson's disease (PD) and the understanding of the point in time of first occurrence is essential for the early detection of incident PD. In this three-center longitudinal, observational study, we evaluated the specific risk for PD associated with single or combinations of risk factors and prodromal markers. In addition, we evaluated which risk factors and prodromal markers emerge at which time before the diagnosis of PD. Of the 1,847 at-baseline PD-free individuals ≥ 50 years, 1,260 underwent the 5-year follow-up assessment. There were 21 cases of incident PD during the study period. Enlarged hyperechogenic substantia nigra was the most frequent baseline sign in individuals developing PD after 3 years (80.0 %) and 5 years (85.7 %) compared to healthy controls (17.5 %) followed by the occurrence of mild parkinsonian signs and hyposmia. Evaluation of the signs at the first follow-up assessment showed that individuals developing PD after two additional years showed the same pattern of signs as individuals who developed PD 3 years after baseline assessment.

Enlarged hyperechogenic substantia nigra as a risk marker for Parkinson's disease.

BACKGROUND: SN hyperechogenicity (SN+), determined by transcranial sonography, has been proposed as a risk factor for Parkinson's disease (PD). Recently, we reported a 17.4-fold increased risk for PD in individuals with SN+ older than 50 years within 3 years. METHODS: This is the second follow-up of a prospective, longitudinal, three-center observational study after 5 years. Of the initial 1,847 at baseline PD-free participants 50 years or older, 1,271 underwent the 5-year reassessment. RESULTS: Within 5 years, 21 individuals developed incident PD. Participants with SN+ at baseline had a more than 20.6 times increased risk to develop PD in this time span than those without this echo feature. CONCLUSION: We thus confirm our finding of the 3-year follow-up examination in a longer observation time and higher number of individuals with incident PD and suggest SN+ as an important risk marker for PD.

Cognitive profiles in Parkinson's disease and their relation to dementia: a data-driven approach.

Parkinson's disease is characterized by a substantial cognitive heterogeneity, which is apparent in different profiles and levels of severity. To date, a distinct clinical profile for patients with a potential risk of developing dementia still has to be identified. We introduce a data-driven approach to detect different cognitive profiles and stages. Comprehensive neuropsychological data sets from a cohort of 121 Parkinson's disease patients with and without dementia were explored by a factor analysis to characterize different cognitive domains. Based on the factor scores that represent individual performance in each domain, hierarchical cluster analyses determined whether subgroups of Parkinson's disease patients show varying cognitive profiles. A six-factor solution accounting for 65.2% of total variance fitted best to our data and revealed high internal consistencies (Cronbach's alpha coefficients >0.6). The cluster analyses suggested two independent patient clusters with different cognitive profiles. They differed only in severity of cognitive impairment and self-reported limitation of activities of daily living function but not in motor performance, disease duration, or dopaminergic medication. Based on a data-driven approach, divers cognitive profiles were identified, which separated early and more advanced stages of cognitive impairment in Parkinson's disease without dementia. Importantly, these profiles were independent of motor progression.

Lowered serum amyloid-ß1-42 autoantibodies in individuals with lifetime depression.

Reduced levels of naturally occurring autoantibodies against amyloid-ß (Aß) have been described in Alzheimer's disease (AD). Lifetime depression doubles the risk of AD, thus these autoantibodies may also be reduced in this group. We measured serum IgG autoantibody titers against Aß1-42, S100b and α-synuclein in 214 individuals with depression and 419 controls. Titers against Aß1-42 were lower in individuals with lifetime depression (5544.6 ± 389.3) compared to controls (7208.7 ± 482.4; p = 0.048). Titers against S100b and α-synuclein were comparable between the cohorts. These data suggest an AD-like impairment of the humoral immune response in a relevant proportion of individuals with depression.

Characterizing POLG ataxia: clinics, electrophysiology and imaging.

Mutations in the mitochondrial DNA polymerase gamma (POLG) cause a highly pleomorphic disease spectrum, and reports about their frequencies in ataxia populations yield equivocal results. This leads to uncertainties about the role of POLG genetics in the workup of patients with unexplained ataxia. A comprehensive characterization of POLG-associated ataxia (POLG-A) will help guide genetic diagnostics and advance our understanding of the disease processes underlying POLG-A. Thirteen patients with POLG-A were assessed by standardized clinical investigation, nerve conduction studies, motor-evoked potentials, magnetic resonance imaging (MRI) and transcranial sonography (TCS). The findings were compared with 13 matched patients with Friedreich's ataxia (FA). In addition to the well-known POLG-associated features of chronic external ophthalmoplegia (100 %), areflexia to the lower extremity (100 %), impaired vibration sense (100 %), bilateral ptosis (69 %) and epilepsy (38 %), also hyperkinetic movement disorders were frequent in POLG-A patients, including chorea (31 %), dystonia (31 %) and myoclonus (23 %). Similar to FA, polyneuropathy was of sensory axonal type (100 %). In contrast to FA, none of the POLG-A patients showed impaired central motor conduction. TCS demonstrated less enlargement of the fourth ventricle and more diffuse cerebellar hyperechogenicity in POLG-A. Corresponding to TCS, MRI revealed no or only mild cerebellar atrophy in most POLG-A patients (85 %). POLG ataxia presents with the clinical characteristics of both afferent and cerebellar ataxia. Cerebellar alterations diffusely involve various parts of the cerebellum, yet cerebellar atrophy is generally mild. POLG-A presents with a high load of distinct non-ataxia features, namely, sensory neuropathy, external ophthalmoplegia, ptosis, epilepsy and/or hyperkinetic movement disorders. Involvement of the corticospinal tract, however, is rare.

Neuroimaging: current role in detecting pre-motor Parkinson's disease.

Convergent evidence suggests a pre-motor period in Parkinson's disease (PD) during which typical motor symptoms have not yet developed although dopaminergic neurons in the substantia nigra have started to degenerate. Advances in different neuroimaging techniques have allowed the detection of functional and structural changes in early PD. This review summarizes the state of the art knowledge concerning structural neuroimaging techniques including magnetic resonance imaging (MRI) and transcranial B-mode-Doppler-sonography (TCS) as well as functional neuroimaging techniques using radiotracer imaging (RTI) with different radioligands in detecting pre-motor PD.

Poor trail making test performance is directly associated with altered dual task prioritization in the elderly--baseline results from the TREND study.

BACKGROUND: Deterioration of executive functions in the elderly has been associated with impairments in walking performance. This may be caused by limited cognitive flexibility and working memory, but could also be caused by altered prioritization of simultaneously performed tasks. To disentangle these options we investigated the associations between Trail Making Test performance--which specifically measures cognitive flexibility and working memory--and dual task costs, a measure of prioritization. METHODOLOGY AND PRINCIPAL FINDINGS: Out of the TREND study (Tuebinger evaluation of Risk factors for Early detection of Neurodegenerative Disorders), 686 neurodegeneratively healthy, non-demented elderly aged 50 to 80 years were classified according to their Trail Making Test performance (delta TMT; TMT-B minus TMT-A). The subjects performed 20 m walks with habitual and maximum speed. Dual tasking performance was tested with walking at maximum speed, in combination with checking boxes on a clipboard, and subtracting serial 7 s at maximum speeds. As expected, the poor TMT group performed worse when subtracting serial 7 s under single and dual task conditions, and they walked more slowly when simultaneously subtracting serial 7 s, compared to the good TMT performers. In the walking when subtracting serial 7 s condition but not in the other 3 conditions, dual task costs were higher in the poor TMT performers (median 20%; range -6 to 58%) compared to the good performers (17%; -16 to 43%; p<0.001). To the contrary, the proportion of the poor TMT performance group that made calculation errors under the dual tasking situation was lower than under the single task situation, but higher in the good TMT performance group (poor performers, -1.6%; good performers, +3%; p = 0.035). CONCLUSION: Under most challenging conditions, the elderly with poor TMT performance prioritize the cognitive task at the expense of walking velocity. This indicates that poor cognitive flexibility and working memory are directly associated with altered prioritization.