Combining ultrasound and microelectrode recordings for postoperative localization of subthalamic electrodes in Parkinson's disease.

OBJECTIVE: To assess transcranial sonography (TCS) as stand-alone tool and in combination with microelectrode recordings (MER) as a method for the postoperative localization of deep brain stimulation (DBS) electrodes in the subthalamic nucleus (STN). METHODS: Individual dorsal and ventral boundaries of STN (n = 12) were determined on intraoperative MER. Postoperatively, a standardized TCS protocol was applied to measure medio-lateral, anterior-posterior and rostro-caudal electrode position using visualized reference structures (midline, substantia nigra). TCS and combined TCS-MER data were validated using fusion-imaging and clinical outcome data. RESULTS: Test-retest reliability of standard TCS measures of electrode position was excellent. Computed tomography and TCS measures of distance between distal electrode contact and midline agreed well (Pearson correlation; r = 0.86; p < 0.001). Comparing our "gold standard" of rostro-caudal electrode localization relative to STN boundaries, i.e. combining MRI-based stereotaxy and MER data, with the combination of TCS and MER data, the measures differed by 0.32 ± 0.87 (range, -1.35 to 1.25) mm. Combined TCS-MER data identified the clinically preferred electrode contacts for STN-DBS with high accuracy (Cohens kappa, 0.86). CONCLUSIONS: Combined TCS-MER data allow for exact localization of STN-DBS electrodes. SIGNIFICANCE: Our method provides a new option for monitoring of STN-DBS electrode location and guidance of DBS programming in Parkinson's disease.

Novel Object Recognition in Rats With NMDAR Dysfunction in CA1 After Stereotactic Injection of Anti-NMDAR Encephalitis Cerebrospinal Fluid.

Purpose: Limbic encephalitis associated with autoantibodies against N-methyl D-aspartate receptors (NMDARs) often presents with memory impairment. NMDARs are key targets for memory acquisition and retrieval, and have been mechanistically linked to its underlying process, synaptic plasticity. Clinically, memory deficits are largely compatible with a pre-dominantly hippocampus-dependent phenotype, which, in rodents, is principally involved in spatial memory. Previous studies confirmed the impaired spatial memory in the rat model of anti-NMDAR encephalitis. Here, we hypothesized that non-spatial memory functions, such as object recognition might also be affected in this model. Methods: We performed stereotactic intrahippocampal bolus injection of human cerebrospinal fluid (CSF) from anti-NMDAR encephalitis and control patients into the hippocampus of the anesthetized rat. After recovery for 1-8 days, hippocampal slices were prepared from these animals and NMDAR-dependent long-term potentiation was assessed at the Schaffer collateral-CA1 synapse. In addition, we performed behavioral analyses using the open field and novel object recognition tasks. Results: NMDAR-dependent long-term potentiation in the hippocampal CA1 area was significantly suppressed, indicating successful NMDAR dysfunction in this subfield. Spontaneous locomotor activity as well as anxiety-related behavior in the open field did not differ between NMDAR-CSF-treated and control animals. In the novel object recognition task, there were no differences in the motivation to approach objects. In contrast, we observed a significantly preferred exploration of the novel object only in control, but not in NMDAR-CSF-treated rats. Conclusion: These results indicate that NMDAR dysfunction obtained by intrahippocampal stereotactic injection does not alter locomotor or anxiety-related behavior. In addition, approach to an object or exploratory behavior in general are not affected either, but intact initial NMDAR-dependent processes might be involved in novel object recognition.

Atrophy of the Vagus Nerve in Parkinson's Disease Revealed by High-Resolution Ultrasonography.

Background: The vagus nerve has been suggested to represent one major route of disease progression in Parkinson's disease (PD). Here, we examined whether patients with idiopathic PD exhibit an atrophy of the vagus nerve in comparison to age-matched controls. Methods: In this cross-sectional study, performed between July 2017 and January 2018, we measured the caliber (cross-sectional area) of the mid-cervical vagus, accessory and phrenic nerves in 20 patients with PD (disease duration: 10.1 ± 7.4 years) and 61 (including 20 age-matched) controls using high-resolution ultrasonography. Ultrasonography and assessments of autonomic function were performed by blinded raters. Results: Mean vagus nerve calibers were lower in patients with PD compared to age-matched controls (right: 0.64 ± 0.17 vs. 1.04 ± 0.20; left: 0.69 ± 0.18 vs. 0.87 ± 0.15 mm2; p < 0.001) while accessory and phrenic nerve calibers did not differ. In controls, age correlated negatively with calibers of the accessory and the phrenic nerve (each p ≤ 0.001), and trended to correlate with vagus nerve caliber (p = 0.023). In patients with PD and age-matched controls combined, the summed caliber of the right and left vagus nerves correlated with the burden of autonomic symptoms on the PD Non-Motor Symptoms Questionnaire (r = -0.46; p = 0.003). Moreover, the caliber of the right but not of the left vagus nerve correlated with the parasympathetic domain of heart rate variability (r = 0.58; p = 0.001). Conclusions: PD is associated with a bilateral atrophy of the vagus nerve but not of the spinal accessory or the phrenic nerves. Our findings suggest that viscero-afferent and viscero-efferent vagal fibers are predominantly affected in PD.

Stereotactic injection of cerebrospinal fluid from anti-NMDA receptor encephalitis into rat dentate gyrus impairs NMDA receptor function.

Autoimmune encephalitis is increasingly recognized in patients with otherwise unexplained encephalopathy with epilepsy. Among these, patients with anti-N-methyl D-aspartate receptor (NMDAR) encephalitis present epileptic seizures, memory deficits, and psychiatric symptoms. However, the functional consequences of such autoantibodies are poorly understood. In order to investigate the pathophysiology of this disease, we stereotactically injected either cerebrospinal fluid (CSF) from three anti-NMDAR encephalitis patients or commercially available anti-NMDAR1 into the dentate gyrus of adult female rats. Control animals were injected with either CSF obtained from three epilepsy patients (ganglioglioma, posttraumatic epilepsy, focal cortical dysplasia) lacking anti-NMDAR or saline. Intracellular recordings from dentate gyrus granule cells showed a significant reduction of the NMDAR-evoked excitatory postsynaptic potentials (NMDAR-EPSPs) in animals treated with anti-NMDAR. As a consequence of this, action potential firing in these cells by NMDAR-EPSPs was significantly impaired. Long-term potentiation in the dentate gyrus was also significantly reduced in rats injected with anti-NMDAR as compared to control animals. This was accompanied by a significantly impaired learning performance in the Morris water maze hidden platform task when the animals had been injected with anti-NMDAR antibody-containing CSF. Our findings suggest that anti-NMDAR lead to reduced NMDAR function in vivo which could contribute to the memory impairment found in patients with anti-NMDAR encephalitis.