[Fatal neurological side effect of anti-CD20 antibody treatment]. / Fatale neurologische Nebenwirkung einer Anti-CD20-Antikörper-Therapie.

Progressive multifocal leukoencephalopathy (PML) is a rare, often fatal infection of the central nervous system caused by reactivation of John Cunningham virus (JCV). The case of a 59-year-old woman presenting with neurological disorders after treatment of her relapsed lymphoma with rituximab, among others, is reported. Magnetic resonance imaging showed fast-growing white matter lesions of both hemisphere and cerebellar that were neither space-consuming nor enhancing contrast media. Clinical and radiological suspicion of PML was confirmed by detection of JCV-DNA in cerebrospinal fluid. The patient died from devastating neurological decline only 11 days after the diagnosis was made. Due to the wider indication of monoclonal antibodies in almost every medical specialty we must always consider iatrogenic PML in addition to classic PML associated with acquired immunodeficiency syndrome (AIDS).

Cerebral venous sinus thrombosis after adenovirus-vectored COVID-19 vaccination: review of the neurological-neuroradiological procedure.

Cerebral venous and sinus thrombosis (CVST) after adenovirus-vectored COVID-19 ChAdOx1 nCov-19 (Oxford-AstraZeneca) and Ad26.COV2.S (Janssen/Johnson & Johnson) is a rare complication, occurring mainly in individuals under 60 years of age and more frequently in women. It manifests 4-24 days after vaccination. In most cases, antibodies against platelet factor-4/polyanion complexes play a pathogenic role, leading to thrombosis with thrombocytopenia syndrome (TTS) and sometimes a severe clinical or even fatal course. The leading symptom is headache, which usually increases in intensity over a few days. Seizures, visual disturbances, focal neurological symptoms, and signs of increased intracranial pressure are also possible. These symptoms may be combined with clinical signs of disseminated intravascular coagulation such as petechiae or gastrointestinal bleeding. If TTS-CVST is suspected, checking D-dimers, platelet count, and screening for heparin-induced thrombocytopenia (HIT-2) are diagnostically and therapeutically guiding. The imaging method of choice for diagnosis or exclusion of CVST is magnetic resonance imaging (MRI) combined with contrast-enhanced venous MR angiography (MRA). On T2*-weighted or susceptibility weighted MR sequences, the thrombus causes susceptibility artefacts (blooming), that allow for the detection even of isolated cortical vein thromboses. The diagnosis of TTS-CVST can usually be made reliably in synopsis with the clinical and laboratory findings. A close collaboration between neurologists and neuroradiologists is mandatory. TTS-CVST requires specific regimens of anticoagulation and immunomodulation therapy if thrombocytopenia and/or pathogenic antibodies to PF4/polyanion complexes are present. In this review article, the diagnostic and therapeutic steps in cases of suspected TTS associated CSVT are presented.

Dentate-nucleus gadolinium deposition on magnetic resonance imaging: ultrasonographic and clinical correlates in multiple sclerosis patients.

OBJECTIVE: The objective of this study is to find out whether gadolinium accumulation in the dentate nucleus (DN) after repeated gadolinium-based contrast agent (GBCA) administration in multiple sclerosis (MS) patients is related to tissue alteration detectable on transcranial ultrasound. METHODS: In this case-control study, 34 patients (17 with, and 17 age-, sex-, MS severity-, and duration-matched participants without visually rated DN T1-hyperintensity) who had received 2-28 (mean, 11 ± 7) consecutive 1.5-Tesla MRI examinations with application of linear GBCA were included. Real-time MRI-ultrasound fusion imaging was applied, exactly superimposing the DN identified on MRI to calculate its corresponding echo-intensity on digitized ultrasound image analysis. In addition, cerebellar ataxia and cognitive performance were assessed. Correlation analyses were adjusted for age, MS duration, MS severity, and time between MRI scans. RESULTS: DN-to-pons T1-signal intensity-ratios (DPSIR) were larger in patients with visually rated DN T1-hyperintensity compared to those without (1.16 ± 0.10 vs 1.09 ± 0.06; p = 0.01). In the combined group, DPSIR correlated with the cumulative linear-GBCA dose (r = 0.49, p = 0.003), as did the DPSIR change on last versus first MRI (r = 0.59, p = 0.003). Neither DPSIR nor globus pallidus internus-to-thalamus T1-signal intensity-ratios were related to echo-intensity of corresponding ROI's. DPSIR correlated with the dysarthria (r = 0.57, p = 0.001), but no other, subscore of the International Cooperative Ataxia Rating Scale, and no other clinical score. CONCLUSIONS: DN gadolinium accumulation is not associated with trace metal accumulation, calcification, or other tissue alteration detectable on ultrasound. A possible mild effect of DN gadolinium accumulation on cerebellar speech function in MS patients, suggested by present data, needs to be validated in larger study samples.

Headache Characteristics in the Neurological Emergency Department: A Retrospective Study.

Background: The care of patients with headache in the emergency department (ED) represents a diagnostic and clinical challenge. Data on the prevalence and characteristics of headache patients in purely neurological EDs are sparse. The aim of the present study is to examine patient profiles with the cardinal symptom of headache in an academic neurological ED, to analyze correlations between headache characteristics and search for differences compared to the interdisciplinary ED. Methods: This retrospective cross-sectional study assessed all patients who presented to the ED of the Department of Neurology at Rostock University Medical Center between November 2013 and November 2016 with the main symptom of headache. Epidemiological, clinical, diagnostic data as well as key data regarding the care structure were recorded. Correlations between headache characteristics and diagnosis at discharge were analyzed and risk profiles were identified using binary logistic regression analysis. Conclusion: This study comprehensively characterized a large collective of patients with the cardinal symptom of headache presenting to a purely neurology emergency department.

Effects of insular involvement on functional outcome after intracerebral hemorrhage.

OBJECTIVE: Ischemic stroke, as well as intracerebral hemorrhage (ICH), involving the insular cortex tends to be more severe. The impact of insular involvement on outcome of ICH remains enigmatic. METHODS: We analyzed 159 patients with supratentorial ICH. Depending on insular involvement the patients were classified into two groups (ICHnon-insular vs. ICHinsular ). Volume and symptom severity of ICH were assessed. Electrocardiography, chest X-ray, and laboratory examinations including myocardial enzymes and inflammatory markers were made. In-hospital death and outcome at discharge from hospital were assessed on the modified Rankin scale (mRS). RESULTS: The main finding was an association of insular involvement of ICH with worse short-term outcome as measured by mRS (common odds ratio: 4.08 (95% CI: 2.09-7.92); p < .001). This association survived adjustment to relevant covariates such as age, sex, ICH volume, intraventricular hemorrhage, pneumonia, and length of stay (adjusted common odds ratio: 2.51 (95% CI: 1.21-5.21); p = .014) but had no predictive value for side of ICH or rate of atrial fibrillation. There was no association of ICH localization with in-hospital death rate. CONCLUSION: Insular localization of ICH lesions predicts worse short-term functional outcome independent of side of bleeding or cardiac dysfunction such as new AF. These findings need clarification in larger prospective cohorts assessed by detailed autonomic/cardiac testing, as well as neuroimaging sub-localization of ICH within the insular region.

[Cerebral venous sinus thrombosis after COVID-19 vaccination : Neurological and radiological management]. / Hirnvenen- und Sinusthrombose nach COVID-19-Schutzimpfung : Neurologisch-radiologisches Prozedere.

BACKGROUND: Vaccine-induced cerebral venous and sinus thrombosis (VI-CVST) is a rare complication in recipients of the adenovirus-vectored coronavirus disease 2019 (COVID-19) vaccine ChAdOx1 nCov-19 (Vaxzevria®; AstraZeneca). OBJECTIVES: Development of a diagnostic and therapeutic standard. MATERIALS AND METHODS: Analysis of clinical and basic research findings, expert opinions, and experience with our own cases. RESULTS: VI-CVST usually manifests on day 4-24 after vaccination, mostly in individuals aged < 60 years, and women. In the majority there is an immune pathogenesis caused by antibodies against platelet factor 4/polyanion complexes, leading to thrombotic thrombocytopenia which can result in severe, sometimes fatal, course. The cardinal symptom is headache worsening within days which, however, also can be of variable intensity. Other possible symptoms are seizures, visual disturbance, focal neurological deficits and signs of increased intracranial pressure. If VI-CVST is suspected, the determination of plasma D­dimer level, platelet count, and screening for heparin-induced thrombocytopenia (HIT-2) are essential for treatment decision-making. Magnetic resonance imaging (MRI) with venous MR-angiography is the neuroimaging modality of choice to confirm or exclude VI-CVST. On T2* susceptibility-weighted MRI, the clot in the sinuses or veins produces marked susceptibility artifacts ("blooming"), which also enables the detection of isolated cortical venous thromboses. MRI/MR-angiography or computed tomography (CT)/CT-angiography usually allow-in combination with clinical and laboratory findings-reliable diagnosis of VI-CVST. CONCLUSIONS: The clinical suspicion of VI-CVST calls for urgent laboratory and neuroimaging workup. In the presence of thrombocytopenia and/or pathogenic antibodies, specific medications for anticoagulation and immunomodulation are recommended.

Adenovirus-Vectored COVID-19 Vaccine-Induced Immune Thrombosis of Carotid Artery: A Case Report.

OBJECTIVE: Venous thromboses and thrombocytopenia after vaccination with the adenovirus-vectored COVID-19 vaccine ChAdOx1 nCov-19 (AstraZeneca) have been linked to serum antibodies against platelet factor 4 (PF4)-polyanion complexes. We here report vaccine-induced isolated carotid arterial thrombosis. METHODS: Imaging and laboratory findings, treatment decisions and outcome of this case are presented. RESULTS: Eight days after having received the first dose of ChAdOx1 nCov-19 vaccine, a 31-year-old man was admitted to our stroke unit with acute headache, aphasia, and hemiparesis. D-dimers were slightly elevated, but platelet count and fibrinogen level were normal. MRI-confirmed mainstem occlusion of middle cerebral artery resolved within 1 hour after start of IV thrombolysis. A wall-adherent, non-occluding thrombus in the ipsilateral carotid bulb was identified as the source of embolism. Cardiac or paradoxical (venous) embolism was excluded. Screening for presence of heparin-induced thrombocytopenia-related antibodies was positive, and highly elevated serum IgG antibodies against PF4-polyanion complexes were subsequently proven. Treatment with aspirin and subcutaneous danaparoid, followed by phenprocoumon, led to thrombus shrinkage and dissolution within 19 days, and favorable clinical outcome. DISCUSSION: Vaccine history is important in patients not only with venous but also with arterial thromboembolic events. Vaccine-induced immune thrombosis of brain-supplying arteries may well be handled.

Stereotactically Injected Kv1.2 and CASPR2 Antisera Cause Differential Effects on CA1 Synaptic and Cellular Excitability, but Both Enhance the Vulnerability to Pro-epileptic Conditions.

PURPOSE: We present a case of voltage-gated potassium channel (VGKC) complex antibody-positive limbic encephalitis (LE) harboring autoantibodies against Kv1.2. Since the patient responded well to immunotherapy, the autoantibodies were regarded as pathogenic. We aimed to characterize the pathophysiological role of this antibody in comparison to an antibody against the VGKC-associated protein contactin-associated protein-2 (CASPR2). METHODS: Stereotactic injection of patient sera (anti-Kv1.2-associated LE or anti-CASPR2 encephalopathy) and a control subject was performed into the hippocampus of the anesthetized rat in vivo, and hippocampal slices were prepared for electrophysiological purposes. Using extra- and intracellular techniques, synaptic transmission, long-term potentiation (LTP) and vulnerability to pro-epileptic conditions were analyzed. RESULTS: We observed that the slope of the field excitatory postsynaptic potential (fEPSP) was significantly increased at Schaffer collateral-CA1 synapses in anti-Kv1.2-treated and anti-CASPR2-treated rats, but not at medial perforant path-dentate gyrus synapses. The increase of the fEPSP slope in CA1 was accompanied by a decrease of the paired-pulse ratio in anti-Kv1.2, but not in anti-CASPR2 tissue, indicating presynaptic site of anti-Kv1.2. In addition, anti-Kv1.2 tissue showed enhanced LTP in CA1, but dentate gyrus LTP remained unaltered. Importantly, LTP in slices from anti-CASPR2-treated animals did not differ from control values. Intracellular recordings from CA1 neurons revealed that the resting membrane potential and a single action potential were not different between anti-Kv1.2 and control tissue. However, when the depolarization was prolonged, the number of action potentials elicited was reduced in anti-Kv1.2-treated tissue compared to both control and anti-CASPR2 tissue. In contrast, polyspike discharges induced by removal of Mg2+ occurred earlier and more frequently in both patient sera compared to control. CONCLUSION: Patient serum containing anti-Kv1.2 facilitates presynaptic transmitter release as well as postsynaptic depolarization at the Schaffer-collateral-CA1 synapse, but not in the dentate gyrus. As a consequence, both synaptic transmission and LTP in CA1 are facilitated and action potential firing is altered. In contrast, anti-CASPR2 leads to increased postsynaptic potentials, but without changing LTP or firing properties suggesting that anti-Kv1.2 and anti-CASPR2 differ in their cellular effects. Both patient sera alter susceptibility to epileptic conditions, but presumably by different mechanisms.

Mirror Movements in Amyotrophic Lateral Sclerosis: A Combined Study Using Diffusion Tensor Imaging and Transcranial Magnetic Stimulation.

Objective: Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disorder predominantly affecting the motor system. In a number of patients, mirror movements (MMs) suggest involvement of transcallosal fiber tracts in conjunction with upper motor neuron involvement. The aim of the study was to elucidate functional and structural alterations of callosal integrity in ALS patients with MMs. Methods: Nineteen patients with ALS displaying MMs and 20 controls underwent clinical assessment, transcranial magnetic stimulation (TMS), and diffusion tensor imaging (DTI). TBSS (tract based spatial statistics) was performed. We investigated ipsilateral silent period (iSP) as a measure of transcallosal inhibition, and diffusion changes in the corpus callosum and corticospinal tract (CST) as measure of structural integrity. Results: In ALS patients TMS revealed a longer mean iSP latency than controls. Twelve ALS patients (63.2%) showed loss of iSP, but none of the controls. Using region of interest analysis, fractional anisotropy (FA) values of the CST were significantly lower in ALS patients compared with controls, but diffusion parameters of the corpus callosum did not differ between patients and controls. The lack of diffusion changes in the corpus callosum was confirmed in whole brain tract based statistics, assessing FA as well as mean, radial, and axial diffusivity. There was a significant negative correlation between resting motor threshold and FA values of the CST, but not between iSP and FA of the corpus callosum. Conclusion: In conclusion the study failed to show microstructural changes in the corpus callosum in conjunction with MMs. One possible reason may be that functional disturbance of transcallosal pathways precede microstructural changes in the corpus callosum.

A case report: Numb Chin Syndrome due to thalamic infarction: a rare case.

BACKGROUND: Numb Chin Syndrome (NCS), which is also characterized as sensory neuropathy of the mental nerve, describes a mostly unilateral numbness of the chin and lower lip. Benign and malignant diseases are known to cause this circumscribed symptom, which can easily be overlooked or misdiagnosed. In this article we present the very rare case of a clinical NCS caused by thalamic lacunar infarction. As a pure sensory stroke it is a rare variant of the Cheiro-Oral Syndrome (COS). CASE PRESENTATION: A 63-year-old male patient received an emergency referral to our department after the patient had noticed a feeling of numbness of the left lower lip and chin on the previous day. The neurological examination revealed an approximately 2 × 3 cm area of hypoesthesia in the area of the chin and left lower lip and the cranial MRI an acute ischemia in the right thalamus. CONCLUSIONS: In this case report we introduce a patient who clinically shows an NCS. Various diseases may be responsible for NCS, including malignancies or even central neurological disorders such as multiple sclerosis. A lacunar thalamic ischemia as a cause of NCS is very rare and to our knowledge described in the literature only in the contex of a COS in three cases. We wish to remind the reader, through this case, of the purely descriptive and syndromal character of the NCS and the importance for detecting underlying diseases. Furthermore we give a brief overview of the NCS and causative disorders.

Epileptic seizures and outcome in different subtypes of subarachnoid haemorrhage - Results of a single-center retrospective analysis.

BACKGROUND: Symptomatic epileptic seizures are an important complication in subarachnoid haemorrhage (SAH) with a frequency of 0.9-25% with importance for patient outcome. The majority of previous studies investigated the incidence of symptomatic epileptic seizures after aneurysmatic SAH. Here we compared the seizure incidence and its impact on the outcome between non-aneurysmatic and aneurysmatic SAH. METHODS: We analysed retrospectively 109 consecutive patients with spontaneous, non-traumatic SAH. Patients were divided in three groups (perimesencephalic, non-aneurysmatic and aneurysmatic SAH). All patients received standard-of-care treatment. The occurrence of acute (0-7 days after SAH) and remote symptomatic epileptic seizures (7 days or more after SAH), severity of SAH as well as clinical outcome parameters (modified Rankin scale [mRS]) at discharge and the frequency of in-house complications were assessed. mRS scores were dichotomized in 0-3 vs. 4-6 to stratify for good versus bad outcome. RESULTS: Perimesencephalic SAH patients did not experience acute seizures whereas non-aneurysmatic and aneurysmatic SAH patients showed acute seizures with similar frequency (9% and 11%, p = 0.23). The frequency of remote symptomatic seizures was similar in all subgroups (12% vs. 9% vs. 7%, p = 0.72). Seizure occurrence was not predictive for a poor outcome (mRS >4; acute seizures: OR 0.35 [95%CI: 0.02-6.96], p = 0.49; remote seizures: OR 1.72 [95%CI: 0.14-20.1], p = 0.67). CONCLUSIONS: Seizures are important neurologic complications of SAH of all etiologies. Nevertheless, acute as well as remote symptomatic seizures are unrelated to the short-term outcome. These results should be treated as hypothesis generating and require confirmation.

Correction: The prognostic value of neurofilament levels in patients with sepsis-associated encephalopathy - A prospective, pilot observational study.

[This corrects the article DOI: 10.1371/journal.pone.0211184.].

The prognostic value of neurofilament levels in patients with sepsis-associated encephalopathy - A prospective, pilot observational study.

Sepsis-associated encephalopathy (SAE) contributes to mortality and neurocognitive impairment of sepsis patients. Neurofilament (Nf) light (NfL) and heavy (NfH) chain levels as biomarkers for neuroaxonal injury were not evaluated in cerebrospinal fluid (CSF) and plasma of patients with sepsis-associated encephalopathy (SAE) before. We conducted a prospective, pilot observational study including 20 patients with septic shock and five patients without sepsis serving as controls. The assessment of SAE comprised a neuropsychiatric examination, electroencephalography (EEG), magnetic resonance imaging (MRI) and delirium screening methods including the confusion assessment method for the ICU (CAM-ICU) and the intensive care delirium screening checklist (ICDSC). CSF Nf measurements in sepsis patients and longitudinal plasma Nf measurements in all participants were performed on days 1, 3 and 7 after study inclusion. Plasma NfL levels increased in sepsis patients over time (p = 0.0063) and remained stable in patients without sepsis. Plasma NfL values were significantly higher in patients with SAE (p = 0.011), significantly correlated with the severity of SAE represented by ICDSC values (R = 0.534, p = 0.022) and correlated with a poorer functional outcome after 100 days (R = -0.535, p = 0.0003). High levels of CSF Nf were measured in SAE patients. CSF NfL levels were higher in non-survivors (p = 0.012) compared with survivors and correlated with days until death (R = -0.932, p<0.0001) and functional outcome after 100 days (R = -0.749, p<0.0001). The present study showed for the first time that Nf levels provide complementary prognostic information in SAE patients indicating a higher chance of death and poorer functional/cognitive outcome in survivors.

Diagnostic value of NT-proCNP compared to NSE and S100B in cerebrospinal fluid and plasma of patients with sepsis-associated encephalopathy.

Sepsis-associated encephalopathy (SAE) has significant impact on the neurocognitive outcome of sepsis survivors. This study was conducted to analyze the amino-terminal propeptide of the C-type natriuretic peptide (NT-proCNP) as a biomarker for SAE in comparison to neuron-specific enolase (NSE) and S100B protein. Cerebrospinal fluid (CSF) and plasma samples from twelve septic patients with SAE and nine non-septic controls without encephalopathy were analyzed. The assessment of SAE comprised a neuropsychiatric examination, delirium screening using the confusion assessment method in the ICU (CAM-ICU) and magnetic resonance imaging (MRI) in all participants. NSE, S100B and NT-proCNP were measured in plasma at study days 1, 3 and 7 in sepsis patients, once in controls and once in the CSF of both groups. The long-term outcome was assessed using the validated Barthel index (BI). Plasma NT-proCNP levels were significantly higher in the sepsis cohort compared to controls with peak concentrations at study day 1 (10.1 ± 6.6 pmol/l vs. 3.3 ± 0.9 pmol/l; p < 0.01) and a decrease over time. Plasma NT-proCNP levels at day 7 correlated with NT-proCNP in CSF (r = 0.700, p < 0.05). A comparable decrease of significantly higher plasma S100B values in sepsis patients compared to controls was observed. Plasma NSE levels were not significantly different between both groups. CSF NT-proCNP levels just tended to be higher in sepsis patients compared to controls and tended to be higher in patients with septic brain lesions seen on MRI. In the sepsis cohort CSF NT-proCNP levels correlated with CSF Interleukin-6 (IL-6) levels (r = 0.616, p < 0.05) and systemic inflammation represented by high plasma procalcitonin (PCT) levels at day 3 (r = 0.727, p < 0.05). The high peak concentration of plasma NT-proCNP in the early phase of sepsis might help to predict the emergence of SAE during the further course of disease. NT-proCNP in plasma might, in contrast to CSF, indicate neurological impairment in patients with SAE.

Translational evidence for two distinct patterns of neuroaxonal injury in sepsis: a longitudinal, prospective translational study.

BACKGROUND: Brain homeostasis deteriorates in sepsis, giving rise to a mostly reversible sepsis-associated encephalopathy (SAE). Some survivors experience chronic cognitive dysfunction thought to be caused by permanent brain injury. In this study, we investigated neuroaxonal pathology in sepsis. METHODS: We conducted a longitudinal, prospective translational study involving (1) experimental sepsis in an animal model; (2) postmortem studies of brain from patients with sepsis; and (3) a prospective, longitudinal human sepsis cohort study at university laboratory and intensive care units (ICUs). Thirteen ICU patients with septic shock, five ICU patients who died as a result of sepsis, fourteen fluid-resuscitated Wistar rats with fecal peritonitis, eleven sham-operated rats, and three human and four rat control subjects were included. Immunohistologic and protein biomarker analysis were performed on rat brain tissue at baseline and 24, 48, and 72 h after sepsis induction and in sham-treated rats. Immunohistochemistry was performed on human brain tissue from sepsis nonsurvivors and in control patients without sepsis. The clinical diagnostics of SAE comprised longitudinal clinical data collection and magnetic resonance imaging (MRI) and electroencephalographic assessments. Statistical analyses were performed using SAS software (version 9.4; SAS Institute, Inc., Cary, NC, USA). Because of non-Gaussian distribution, the nonparametric Wilcoxon test general linear models and the Spearman correlation coefficient were used. RESULTS: In postmortem rat and human brain samples, neurofilament phosphoform, ß-amyloid precursor protein, ß-tubulin, and H&E stains distinguished scattered ischemic lesions from diffuse neuroaxonal injury in septic animals, which were absent in controls. These two patterns of neuroaxonal damage were consistently found in septic but not control human postmortem brains. In experimental sepsis, the time from sepsis onset correlated with tissue neurofilament levels (R = 0.53, p = 0.045) but not glial fibrillary acidic protein. Of 13 patients with sepsis who had clinical features of SAE, MRI detected diffuse axonal injury in 9 and ischemia in 3 patients. CONCLUSIONS: Ischemic and diffuse neuroaxonal injury to the brain in experimental sepsis, human postmortem brains, and in vivo MRI suggest these two distinct lesion types to be relevant. Future studies should be focused on body fluid biomarkers to detect and monitor brain injury in sepsis. The relationship of neurofilament levels with time from sepsis onset may be of prognostic value. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02442986 . Registered on May 13, 2015.

Magnetic resonance-transcranial ultrasound fusion imaging: A novel tool for brain electrode location.

BACKGROUND: A combination of preoperative magnetic resonance imaging (MRI) with real-time transcranial ultrasound, known as fusion imaging, may improve postoperative control of deep brain stimulation (DBS) electrode location. Fusion imaging, however, employs a weak magnetic field for tracking the position of the ultrasound transducer and the patient's head. Here we assessed its feasibility, safety, and clinical relevance in patients with DBS. METHODS: Eighteen imaging sessions were conducted in 15 patients (7 women; aged 52.4 ± 14.4 y) with DBS of subthalamic nucleus (n = 6), globus pallidus interna (n = 5), ventro-intermediate (n = 3), or anterior (n = 1) thalamic nucleus and clinically suspected lead displacement. Minimum distance between DBS generator and magnetic field transmitter was kept at 65 cm. The pre-implantation MRI dataset was loaded into the ultrasound system for the fusion imaging examination. The DBS lead position was rated using validated criteria. Generator DBS parameters and neurological state of patients were monitored. RESULTS: Magnetic resonance-ultrasound fusion imaging and volume navigation were feasible in all cases and provided with real-time imaging capabilities of DBS lead and its location within the superimposed magnetic resonance images. Of 35 assessed lead locations, 30 were rated optimal, three suboptimal, and two displaced. In two cases, electrodes were re-implanted after confirming their inappropriate location on computed tomography (CT) scan. No influence of fusion imaging on clinical state of patients, or on DBS implantable pulse generator function, was found. CONCLUSIONS: Magnetic resonance-ultrasound real-time fusion imaging of DBS electrodes is safe with distinct precautions and improves assessment of electrode location. It may lower the need for repeated CT or MRI scans in DBS patients.

Disappearance of breach rhythm heralding recurrent tumor progression in a patient with astrocytoma.

The breach rhythm is sometimes considered the consequence of reduced resistance between the cortex and the scalp electrode in the region of a skull defect. On the other hand, the electroencephalographic (EEG) changes after craniotomy were attributed to an activation of EEG activity by meningocortical adhesions with admixed gliosis. We report changes of the breach rhythm in a patient with astrocytoma, which give further evidence that the breach rhythm is not merely the result of physical changes in the area of a skull defect. In our patient, the breach rhythm was no longer detectable before a new tumor progression took place, showed up again, and at the end changed into localized slowing before the deterioration of the patient's general medical condition. This case suggests that in patients with brain tumors, the loss or attenuation in frequency of an established breach rhythm might be considered as an indication of a new tumor progression.

Clinical, genetic, and brain sonographic features related to Parkinson's disease in Gaucher disease.

Homozygous or compound heterozygous mutations in the glucocerebrosidase gene cause Gaucher disease. Moreover, heterozygous glucocerebrosidase gene mutations represent the most common genetic risk factor for Parkinson's disease (PD) known so far. Substantia nigra (SN) hyperechogenicity, a sonographic feature thought to reflect iron accumulation, has been described in both PD and Gaucher disease patients. Here we studied how clinical, genetic, and brain sonographic findings relate to the occurrence of PD in Gaucher disease. Sixteen Gaucher disease patients, 12 PD patients, and 32 control subjects were enrolled. The glucocerebrosidase genotypes were identified by DNA sequencing. All subjects underwent transcranial ultrasound, and eight Gaucher disease patients additionally MRI for comparison with SN ultrasound findings. SN hyperechogenicity and reduced echogenicity of brainstem raphe were more frequent in Gaucher disease patients (62, 37 %) than in controls (12, 12 %; p < 0.001, p < 0.05). SN hyperechogenicity in Gaucher disease patients was unrelated to type or severity of glucocerebrosidase gene mutation, but correlated with iron-sensitive MRI-T2 hypointensity of SN pars compacta, and with age at start of enzyme replacement therapy. While none of the five Gaucher disease patients with signs of PD (definite PD, n = 4; early PD, n = 1) had severe glucocerebrosidase gene mutations known to cause neuronopathic Gaucher disease, all carried a N370S allele, previously reported to predict non-neuronopathic Gaucher disease. Hyposmia, higher non-motor symptoms score (constipation, depression, executive dysfunction), and SN hyperechogenicity were characteristic features of Gaucher disease-related PD. We conclude that the combined clinical, genetic, and transcranial sonographic assessment may improve the PD risk evaluation in Gaucher disease.

Effects of intranasal oxytocin on the neural basis of face processing in autism spectrum disorder.

BACKGROUND: Autism spectrum disorder (ASD) is associated with altered face processing and decreased activity in brain regions involved in face processing. The neuropeptide oxytocin has been shown to promote face processing and modulate brain activity in healthy adults. The present study examined the effects of oxytocin on the neural basis of face processing in adults with Asperger syndrome (AS). METHODS: A group of 14 individuals with AS and a group of 14 neurotypical control participants performed a face-matching and a house-matching task during functional magnetic resonance imaging. The effects of a single dose of 24 IU intranasally administered oxytocin were tested in a randomized, placebo-controlled, within-subject, cross-over design. RESULTS: Under placebo, the AS group showed decreased activity in the right amygdala, fusiform gyrus, and inferior occipital gyrus compared with the control group during face processing. After oxytocin treatment, right amygdala activity to facial stimuli increased in the AS group. CONCLUSIONS: These findings indicate that oxytocin increases the saliency of social stimuli and in ASD and suggest that oxytocin might promote face processing and eye contact in individuals with ASD as prerequisites for neurotypical social interaction.