Tumefactive demyelinating CNS lesion in a 60-year-old woman with familial Mediterranean fever.

We here report on a 60-year-old woman with familial Mediterranean fever (FMF) who developed cognitive impairment 16 years after initial diagnosis. On MRI, a new extensive white matter lesion in the right frontal lobe with mild local mass effect but without contrast enhancement was detectable and classified as a tumefactive lesion. Additional MR spectroscopy showed markedly increased choline levels accompanied by a significant lactate peak, highly suggestive of a low-florid demyelinating process. Although diffuse central nervous system (CNS) lesions have been described in single FMF cases, tumefactive lesions have not been observed in FMF patients without concomitant multiple sclerosis. In summary, this case highlights rare differential diagnoses of atypical, inflammatory CNS lesions and the clinical utility of MR spectroscopy.

Heart Rate Variability and Functional Outcomes of Patients with Spontaneous Intracerebral Hemorrhage.

BACKGROUND: The relationship between heart rate variability (HRV) changes potentially indicating autonomic dysregulation following spontaneous intracerebral hemorrhage (ICH) and functional outcome has not yet been fully elucidated. This study investigated the effects of HRV during the initial 96 h after admission on 90-day functional outcome in ICH patients. METHODS: We included patients with spontaneous ICH in a prospective cohort single-center study. Continuous HR data were retrieved from the Intellispace Critical Care and Anesthesia information system (Philips Healthcare) and analyzed within the following time intervals: 0-2, 0-8, 0-12, 0-24, 0-48, 0-72, and 8-16, 16-24, 24-48, 48-72, 72-96 h after admission. HRV was determined from all available HR values by calculating the successive variability (SV), standard deviation (SD), and coefficient of variation (CV). Low HRV was set as SD ≤ 11.4 ms, and high HRV as SD > 11.4 ms. The clinical severity of ICH was assessed using the National Institutes of Health Stroke Scale (NIHSS) and functional outcome using the modified Rankin Scale (mRS). Good functional outcome was defined as mRS 0-2. RESULTS: The cohort included 261 ICH patients (mean age ± SD 69.6 ± 16.5 years, 48.7% female, median NIHSS 6 (2, 12), median ICH score 1 (0, 2), of whom 106 (40.6%) had good functional outcome. All patients had the lowest HRV at admission, which increased during the first two days. Comparing ICH patients with low HRV (n = 141) and high HRV (n = 118), those with good outcome showed significantly lower HRV during the first three days (0-72 h: HRV SD good outcome 10.6 ± 3.5 ms vs. poor outcome 12.0 ± 4.0 ms; p = 0.004). Logistic regression revealed that advanced age, high premorbid mRS, and high NIHSS at admission were significant predictors of poor functional outcome, while reduced SD of HRV showed a non-significant trend towards good functional outcome (0-72 h: OR 0.898; CI 0.800-1.008; p = 0.067). CONCLUSIONS: Our results indicate autonomic dysfunction with sympathetic hyperactivity after spontaneous ICH, as reflected by the evidence of the lower HRV in the first days. Initially increased sympathetic tone appears to have a protective effect, as suggested by the comparatively lower HRV in patients with good functional outcome at the first days.

Diagnosis of Froin's Syndrome by Parallel Analysis of Ventriculoperitoneal Shunt and Lumbar Cerebrospinal Fluid in a Patient with Cervical Spinal Stenosis.

Elevated protein levels in cerebrospinal fluid (CSF) can occur in various pathologies and are sometimes difficult to interpret. We report a 62-year-old male patient with subacute neurological deterioration, progressive tetraparesis, and cytoalbumin dissociation in the lumbar CSF. The patient had a pre-existing cervical spinal stenosis with mild tetraparesis. Based on the initial cytoalbumin dissociation (protein 938 mg/dL, 4 leucocytes/µL), Guillain-Barré syndrome was initially considered. For further diagnosis, a CSF sample was taken from a pre-existing ventriculoperitoneal shunt, which showed a normal protein and cell count considering the patient's age (protein 70 mg/dL, 1 leucocyte/µL). In conclusion, we suggest that intermediate aggravation of tetraparesis was due to pneumonia with septic constellation, and the cytoalbumin dissociation was interpreted as Froin's syndrome (FS) due to spinal stenosis. In this unique case, we were able to prove the -often suspected- case of FS by parallel analysis of ventriculoperitoneal shunt and lumbar CSF. The triad of xanthochromia, high protein levels, and marked coagulation was first described by Georges Froin and occurs in various processes leading to severe spinal stenosis. The altered composition of lumbar CSF might be due to impaired CSF circulation; however, the exact mechanisms of this phenomenon require further investigation.

Cortical reactivity to transcranial magnetic stimulation predicts risk of post-stroke delirium.

OBJECTIVE: Post-stroke delirium (PSD) is a frequent and with regard to outcome unfavorable complication in acute stroke. The neurobiological mechanisms predisposing to PSD remain poorly understood, and biomarkers predicting its risk have not been established. We tested the hypothesis that hypoexcitable or disconnected brain networks predispose to PSD by measuring brain reactivity to transcranial magnetic stimulation with electroencephalography (TMS-EEG). METHODS: We conducted a cross-sectional study in 33 acute stroke patients within 48 hours of stroke onset. Brain reactivity to single-pulse TMS of dorsolateral prefrontal cortex, primary motor cortex and superior parietal lobule of the right hemisphere was quantified by response intensity, effective connectivity, perturbational complexity index (PCIST), and natural frequency of the TMS-EEG response. PSD development was clinically tracked every 8 hours before and for 7 days following TMS-EEG. RESULTS: Fourteen patients developed PSD while 19 patients did not. The PSD group showed lower excitability, effective connectivity, PCIST and natural frequency compared to the non-PSD group. The maximum PCIST over all three TMS sites demonstrated largest classification accuracy with a ROC-AUC of 0.943. This effect was independent of lesion size, affected hemisphere and stroke severity. Maximum PCIST and maximum natural frequency correlated inversely with delirium duration. CONCLUSIONS: Brain reactivity to TMS-EEG can unravel brain network states of reduced excitability, effective connectivity, perturbational complexity and natural frequency that identify acute stroke patients at high risk for development of delirium. SIGNIFICANCE: Findings provide novel insight into the pathophysiology of pre-delirium brain states and may promote effective delirium prevention strategies in those patients at high risk.

No evidence of oligoclonal bands, intrathecal immunoglobulin synthesis and B cell recruitment in acute ischemic stroke.

BACKGROUND: Within the past 10 years, immune mechanisms associated with acute ischemic stroke (AIS) have been brought into focus, but data on B cell activation and intrathecal Ig production is still scarce. In this study, we determined the prevalence of an elevated IgG index, positive oligoclonal bands (OCBs) and chemokine C-X-C motif ligand 13 (CXCL13) levels in the cerebrospinal fluid (CSF) as markers of intrathecal IgG synthesis and B cell activation in patients with AIS. METHODS: In a retrospective study we analyzed the cerebrospinal fluid (CSF) from 212 patients with AIS from December 2013 to May 2018 assessing intrathecal Ig synthesis, OCBs and CXCL13 concentrations. RESULTS: Overall, 5.7% (12/212) of AIS patients showed an intrathecal IgG synthesis, 0.5% (1/212) with isolated elevated IgG index, 5.2% (7/136) isolated positive OCBs and 2.9% (4/136) both elevated IgG index and positive OCBs. CXCL13 levels were elevated in 3.6% (3/83) of the patients. Approximately one third of these patients had simultaneously chronic inflammatory CNS disease (multiple sclerosis, neuromyelitis optica spectrum disorder, neurosarcoidosis). There was no significant association between CSF findings and stroke characteristics including vascular territory, localization, volume, etiology, acute treatment, or blood-brain barrier dysfunction. Intrathecal IgG synthesis was more common in patients with prior stroke. Longitudinal CSF analysis did not reveal any newly-occurring, but instead mostly persistent or even disappearing intrathecal IgG synthesis after AIS. CONCLUSIONS: We found no evidence of a relevant B cell recruitment and intrathecal IgG synthesis in patients with AIS. In fact, the occurrence of intrathecal IgG synthesis was associated with concurrent chronic inflammatory CNS disease or previous stroke. Consequently, in patients with first-ever AIS and intrathecal IgG synthesis, physicians should search for concomitant inflammatory CNS disease.