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.

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.

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.

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.

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.

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.

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.

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.

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.

The patients' perception of prodromal symptoms before the initial diagnosis of Parkinson's disease.

BACKGROUND: Before the occurrence of motor symptoms permits the clinical diagnosis of Parkinson's disease (PD), about or even more than 50% of the dopaminergic neurons of the substantia nigra have degenerated. This time be called the prodromal phase of PD. OBJECTIVE: To evaluate the time span from onset of first prodromal symptoms to the initial diagnosis of PD as well as the order of symptom occurrence. METHODS: Retrospective study of 93 consecutively interviewed PD patients without dementia and 93 sex and age matched controls free of neurodegenerative disorders. A standardized in-house telephone worksheet assessing 19 nonmotor and six early motor signs was used. RESULTS: A total of 98.8% of all patients interviewed reported to have experienced prodromal symptoms prior to receiving the initial diagnosis of PD. Patients noticed an average of 7.6 different symptoms during this time interval. The mean time span between the recalled onset of any one symptom and PD diagnosis was 10.2 years. In both groups, the course of prodromal sign onset was associated with early neuropathological disease stages proposed by Braak. OUTLOOK: These retrospectively gathered data confirm the existence of a long prodromal phase for PD that is consistent with neuropathological staging. A standardized questionnaire assessing such early symptoms may be helpful in identifying subjects at high risk for PD while they are still in the prodromal phase of the disorder.

AFQ056 treatment of levodopa-induced dyskinesias: results of 2 randomized controlled trials.

Study objectives were to assess the efficacy, safety, and tolerability of AFQ056 in Parkinson's disease patients with levodopa-induced dyskinesia. Two randomized, double-blind, placebo-controlled, parallel-group, in-patient studies for Parkinson's disease patients with moderate to severe levodopa-induced dyskinesia (study 1) and severe levodopa-induced dyskinesia (study 2) on stable dopaminergic therapy were performed. Patients received 25-150 mg AFQ056 or placebo twice daily for 16 days (both studies). Study 2 included a 4-day down-titration. Primary outcomes were the Lang-Fahn Activities of Daily Living Dyskinesia Scale (study 1), the modified Abnormal Involuntary Movement Scale (study 2), and the Unified Parkinson's Disease Rating Scale-part III (both studies). Secondary outcomes included the Unified Parkinson's Disease Rating Scale-part IV items 32-33. The primary analysis was change from baseline to day 16 on all outcomes. Treatment differences were assessed. Fifteen patients were randomized to AFQ056 and 16 to placebo in study 1; 14 patients were randomized to each group in study 2. AFQ056-treated patients showed significant improvements in dyskinesias on day 16 versus placebo (eg, Lang-Fahn Activities of Daily Living Dyskinesia Scale, P = .021 [study 1]; modified Abnormal Involuntary Movement Scale, P = .032 [study 2]). No significant changes were seen from baseline on day 16 on the Unified Parkinson's Disease Rating Scale-part III in either study. Adverse events were reported in both studies, including dizziness. Serious adverse events (most commonly worsening of dyskinesias, apparently associated with stopping treatment) were reported by 4 AFQ056-treated patients in study 1, and 3 patients (2 AFQ056-treated patient and 1 in the placebo group) in study 2. AFQ056 showed a clinically relevant and significant antidyskinetic effect without changing the antiparkinsonian effects of dopaminergic therapy. © 2011 Movement Disorder Society.

Restless legs and substantia nigra hypoechogenicity are common features in Friedreich's ataxia.

Friedreich's ataxia (FA) is a multisystemic degenerative disease, but the prevalence of restless legs syndrome (RLS) is unknown. FA patients might be particularly susceptible to develop RLS as FA presents with features commonly associated with RLS, e.g. multisystemic network dysfunction, peripheral neuropathy and disturbances in subcellular brain iron homeostasis. In this work, we assessed the following: (1) the prevalence of RLS; (2) the prevalence of sonographic hypoechogenicity of the substantia nigra (SN), which is known to be associated with idiopathic RLS; and (3) the relation between both in 28 FA patients. Thirty-two percent of the patients suffered from RLS, thus clearly exceeding the prevalence rate in the general population. SN hypoechogenicity was more frequent in FA patients (61%) compared to healthy controls (7%) and was significantly associated with RLS. However, as SN echogenicity also correlated inversely with disease severity, it seems to be related not only to RLS, but also to the neurodegenerative process in FA itself. The high prevalence of RLS in FA patients warrants specific assessment by neurologists involved in the care of FA patients as treatments are readily available. Similar to patients with idiopathic RLS, reduced SN echogenicity is a frequent finding in FA, possibly indicating regional changes in subcellular brain iron regulation in FA.

Three-dimensional magnetic resonance spectroscopic imaging in the substantia nigra of healthy controls and patients with Parkinson's disease.

OBJECTIVES: To investigate the substantia nigra in patients with Parkinson's disease three-dimensional magnetic resonance spectroscopic imaging with high spatial resolution at 3 Tesla was performed. Regional variations of spectroscopic data between the rostral and caudal regions of the substantia nigra as well as the midbrain tegmentum areas were evaluated in healthy controls and patients with Parkinson's disease. METHODS: Nine patients with Parkinson's disease and eight age- and gender-matched healthy controls were included in this study. Data were acquired by using three-dimensional magnetic resonance spectroscopic imaging measurements. The ratios between rostral and caudal voxels of the substantia nigra as well as the midbrain tegmentum areas were calculated for the main-metabolites N-acetyl aspartate, creatine, choline, and myo-inositol. Additionally, the metabolite/creatine ratios were calculated. RESULTS: In all subjects spectra of acceptable quality could be obtained with a nominal voxel size of 0.252 ml. The calculated rostral-to-caudal ratios of the metabolites as well as of the metabolite/creatine ratios showed with exception of choline/creatine ratio significant differences between healthy controls and patients with Parkinson's disease. CONCLUSIONS: The findings from this study indicate that regional variations in N-acetyl aspartate/creatine ratios in the regions of the substantia nigra may differentiate patients with Parkinson's disease and healthy controls.

Transcranial sonography reveals cerebellar, nigral, and forebrain abnormalities in Friedreich's ataxia.

BACKGROUND: Friedreich's ataxia (FA) is essentially characterized by degeneration of the dorsal root ganglia, the dorsal nuclei of Clarke, and the long spinal fiber tracts, yet there is accumulating evidence that neurodegeneration extends beyond these predilection sites. Transcranial sonography (TCS) has evolved as a valuable complementary neuroimaging tool in the assessment of neurodegenerative diseases due to its capacity to well depict structural changes and the accumulation of heavy metals. Its use for assessing cerebellar neurodegeneration, however, has not yet been investigated.Here we investigated whether TCS allows to assess particular features of cerebellar as well as midbrain and forebrain abnormalities in FA. METHODS: Comprehensive TCS imaging of 34 FA patients and 34 age-matched healthy controls. RESULTS: Hyperechogenicity of the dentate nucleus was very frequent in FA patients (85%) and could even be observed in patients with short disease duration, suggesting that dentate alterations are a common and probably early feature of FA. Substantia nigra was significantly hypoechogenic, possibly indicating regional changes in subcellular brain iron regulation. FA patients showed significantly enlarged 4th, 3rd, and lateral ventricles, thus corroborating earlier MRI and postmortem findings of substantial cerebellar and forebrain atrophy in FA. CONCLUSIONS: TCS provides a quick-to-apply and inexpensive in vivo assessment of both cerebellar and noncerebellar abnormalities in FA, in particular highlighting dentate hyperechogenicity as a core feature. It might serve as a promising tool for imaging aspects of cerebellar neurodegeneration also in other neurodegenerative disorders.

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.

Increased serum insulin-like growth factor 1 in early idiopathic Parkinson's disease.

OBJECTIVE: Insulin-like growth factor 1 (IGF-1) provides protection against loss of dopaminergic neurons in animal models of Parkinson's disease (PD). The aim of this study was to measure serum IGF-1 in patients with PD and assess its correlation with the clinical presentation. METHODS: Serum IGF-1 and growth hormone (GH) levels were measured in 12 patients with idiopathic PD and 12 matched healthy controls, three times over a period of 6 months after overnight fasting. Based on the results, serum IGF-1 was measured in six additional, yet untreated, PD patients. RESULTS: IGF-1 values were stable over the whole period (r=0.83-0.93) in patients and controls. IGF-1 was significantly higher in treated PD patients than in controls at all time points (all p<0.001). There were no significant differences in serum GH levels between patients and controls. Receiver operating characteristics showed a cut-off at 114 ng/ml for differentiation of treated patients and controls (area under the curve=0.90). In the patient group, higher serum IGF-1 levels were correlated with shorter disease duration (r=-0.56, p=0.001). In the healthy control group, higher IGF-1 was correlated with slightly impaired motor performance, as measured by the Unified Parkinson's Disease Rating Scale motor score (r=0.46, p=0.005). In the untreated patient group, serum IGF-1 levels were significantly higher than in healthy controls (p<0.001). Applying the cut-off value of 114 ng/ml, all untreated patients were correctly classified as PD patients. CONCLUSION: Increased IGF-1 might be an interesting serum marker for early PD and potentially for subclinical dopaminergic dysfunction.

Poor effect of guideline based treatment of restless legs syndrome in clinical practice.

BACKGROUND: Numerous randomised controlled trials have proved the efficacy of dopaminergic and non-dopaminergic drugs in the treatment of restless legs syndrome (RLS). In contrast, epidemiological data demonstrate generally insufficient RLS treatment in clinical practice. OBJECTIVE: To prospectively assess the success of RLS treatment in the clinical setting and to evaluate potential demographic factors and comorbidities that may influence the response to therapy. METHODS: 100 patients with idiopathic RLS (40% had never received RLS specific treatment before) were examined at baseline and after 12 months. Recommendations for therapy according to RLS treatment guidelines of the German Neurological Society were given at baseline. Primary measures for the success of therapy were reduction of RLS symptoms (IRLS) and improvement of quality of life (RLS-QoL). RESULTS: No statistically significant improvement of IRLS or RLS-QoL was detected after 12 months, in initially untreated or in pretreated patients. Poor treatment success, regarding improvement of RLS symptoms, quality of life and number of RLS related physician contacts was related to the presence of neuropsychiatric comorbidity--that is, somatoform disorders (prevalence 41%), chronic pain (32%), anxiety (20%) and major depression (16%). CONCLUSION: Success of guideline based treatment of RLS appears to be rather poor in clinical practice. Neuropsychiatric comorbidity may be a target for interventions to improve overall outcome.