Rofo 2021; 193(06): 667-671
DOI: 10.1055/a-1265-7209
Neuroradiology

Cerebral Imaging in Patients with COVID-19 and Neurological Symptoms: First Experience from two University Hospitals in Northern Germany

Article in several languages: English | deutsch
Ulf Jensen-Kondering
1  Department of Radiology and Neuroradiology, University Hospital Schleswig-Holstein, Campus Kiel, Germany
,
Alexander Neumann
2  Institute of Neuroradiology, University Hospital Schleswig-Holstein, Campus Lübeck, Germany
,
Nils G. Margraf
3  Department of Neurology, University Hospital Schleswig-Holstein, Campus Kiel, Germany
,
Felix Gövert
3  Department of Neurology, University Hospital Schleswig-Holstein, Campus Kiel, Germany
,
Norbert Brüggemann
4  Department of Neurology, University Hospital Schleswig-Holstein, Campus Lübeck, Germany
,
Domagoj Schunk
5  Emergency Department, University Hospital Schleswig-Holstein, Campus Kiel, Germany
,
Thomas Bahmer
6  Department of Internal Medicine I, University Hospital Schleswig-Holstein, Campus Kiel, Germany
,
Peter Schramm
2  Institute of Neuroradiology, University Hospital Schleswig-Holstein, Campus Lübeck, Germany
,
Stefan Schreiber
6  Department of Internal Medicine I, University Hospital Schleswig-Holstein, Campus Kiel, Germany
,
Olav Jansen
1  Department of Radiology and Neuroradiology, University Hospital Schleswig-Holstein, Campus Kiel, Germany
› Author Affiliations
 

Abstract

Purpose To describe findings on cerebral imaging in patients with COVID-19 and neurological symptoms at two German university hospitals.

Materials and Methods Patients with COVID-19 and neurological symptoms and cerebral imaging (CT or MRI) were included. A chart review regarding neurological symptoms, COVID-19 and imaging findings was conducted.

Results 12 patients (4 females, age 68 ± 12 years) could be included. Three patients had acute findings. Two patients had acute and subacute cerebral ischemia, one patient had additional intracranial hemorrhages and presumed central pontine myelinolysis. One patient had presumed COVID-19-associated pansinusitis.

Conclusion Findings on cerebral imaging in patients with COVID-19 are uncommon and nonspecific. However, cerebral ischemia is regularly encountered and patients should be evaluated for stroke symptoms.

Key Points:

  • Approx. 20 % of patients with COVID-19 develop neurological symptoms.

  • Findings on cerebral imaging in patients with COVID-19 are heterogeneous and nonspecific.

  • The most common findings are cerebral ischemia and hemorrhages.

Citation Format

  • Jensen-Kondering U, Neumann A, Margraf N et al. Cerebral Imaging in Patients with COVID-19 and Neurological Symptoms: First Experience from two University Hospitals in Northern Germany. Fortschr Röntgenstr 2021; 193: 667 – 671


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Introduction

In December 2019, the first cases of pneumonia caused by a novel coronavirus (SARS-CoV2) were identified in Wuhan/China. The virus has since spread around the globe. The disease caused by SARS-CoV2, known as COVID-19, is typically characterized by a respiratory infection with cough and fever. However, other organ systems can also be infected at an early stage in some cases [1] [2]. According to an initial large retrospective analysis from Wuhan, approximately one third (36.4 %) of COVID-19 patients exhibit neurological manifestations [3]. The neuroinvasive potential of coronaviruses is already known. Neurological symptoms were able to be observed in SARS-CoV1 and MERS-CoV patients [4] [5]. At the end of June 2020, 193 243 cases in Germany and 3146 (108.6 per 100 000 inhabitants were reported in Schleswig-Holstein) (https://www.rki.de/DE/Content/InfAZ/N/Neuartiges_Coronavirus/Fallzahlen.html, as of 6/27/2020). In total, 68 patients had been hospitalized at both sites of the University Hospital of Schleswig-Holstein. We report on our first experience with cerebral imaging in COVID-19 patients with neurological symptoms.


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Materials and Methods

All patients infected with SARS-CoV2 who underwent clinically indicated cerebral imaging were retrospectively included. Imaging findings were evaluated with respect to primary and secondary findings. The following were categorized as primary findings: acute pathologies that were the presumably cause of symptoms or presumably occurred during the infection or as a result of the infection. All pathological findings classified as preexisting were considered secondary findings. In addition, demographic data and clinical information regarding SARS-CoV2 infection were recorded.


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Results

12 patients (4 women, 8 men, average age 68 + 12 years) were able to be included ([Table 1a]). Two of the patients were examined after the infection had resolved. Three COVID-19 cases were mild, five were moderate, and four were severe (mild: no hospitalization, hospitalization without oxygen supply, moderate: oxygen supply, severe: intensive care). MRI examination was performed in two patients, CT examination in seven patients (including additional CT angiography in one case), and three additional patients underwent both CT and MRI. All MRI examinations were performed with IV contrast agent.

Table 1a

Clinical and radiological information regarding the included patients in chronological order. Sex and age are not individually specified.

#

site

severity of COVID-19

neurological symptoms, reason for imaging

modality

primary findings

secondary findings

1

Kiel

moderate

confusion

CT

pronounced microangiopathic white matter damage, Old embolic infarcts

2

Kiel

moderate

confusion, fall

CT

minimal microangiopathic white matter damage

3

Kiel

mild

temporary loss of consciousness

CT

pronounced microangiopathic white matter damage, Old embolic infarcts

4

Lübeck

severe

Impaired consciousness

CT, CTA

residuals after AVM surgery

5

Kiel

moderate

confusion, fall

CT

minimal microangiopathic white matter damage

6

Kiel

mild

right paresthesia

MRI, CT

subacute embolic infarcts

arteriosclerosis of the intracranial vessels

7

Kiel

severe

Impaired consciousness

CT, MRI

subacute and acute infarcts, diffuse subarachnoid hemorrhage, cerebellar intracerebral hemorrhage, primarily central pontine myelinolysis

8

Kiel

moderate

headache

MRI

pansinusitis

9

Lübeck

severe

Impaired consciousness

CT

10

Lübeck

mild

dizziness, sudden hearing loss

CT, MRI

11

Lübeck

severe

Impaired consciousness

CT

12

Kiel

moderate

hyposmia and hypogeusia

MRI

In one severe case of COVID-19, a brain stem lesion was detected and classified as presumed central pontine myelinolysis ([Fig. 1]). Two patients had acute and subacute cerebral ischemia ([Fig. 2]). One patient additionally had a combination of subarachnoid and parenchymal hemorrhages ([Fig. 3]). One patient had presumed COVID-19-associated sinusitis based on headache, imaging finding, and a positive PCR for SARS-CoV2 from a nasal swab ([Fig. 4]). None of the patients had acute inflammatory intracranial changes. No acute findings could be identified on imaging in the remaining patients. The most common secondary findings were preexisting microangiopathic white matter damage (n = 4) and old embolic and microangiopathic stroke (n = 2). The neurological symptoms occurred with the start of the other symptoms in six patients, over the course of hospitalization in four cases, and weeks later in two patients. Eight patients experienced complete resolution of their neurological symptoms, one patient was discharged in soporose state, and three patients died ([Table 1b]).

Zoom Image
Fig. 1 Presumed central pontine myelinolysis in a patient with severe and prolonged COVID-19 course. Hyperintense central pontine lesion in T2w images. A with corresponding diffusion impairment B but without contrast enhancement C after contrast agent administration. While hospitalized, the patient showed no hyponatremia and no relevant hypernatremia but now requires dialysis. There were no laboratory findings prior to the patient being transferred to us. Lumbar puncture was not performed.
Zoom Image
Fig. 2 Cerebral ischemia pattern. Bilateral hemodynamic stroke along the inner boundary zone A. Acute left cerebellar infarction in the territory of the inferior posterior cerebellar artery B. Subacute hemorrhagic infarction in the territory of the right posterior cerebral artery C. Subacute infarction of the left thalamus with contrast enhancement D and also small left parietal infarcts.
Zoom Image
Fig. 3 Right cerebellar parenchymal hemorrhage (dark arrow) and bifrontal subarachnoid hemorrhages (light arrows) in a susceptibility-weighted sequence and additional axial FLAIR B, C to show the extraaxial localisation of the bifrontal hemorrhages (light arrows). Prior to acquisition of the MRI scan, anticoagulation therapy was performed to treat a pulmonary artery embolism with low-molecular heparin (tinzaparin) administered subcutaneously followed by unfractionated heparin with a target PTT of 70–80 s and then rivaroxaban and clopidogrel.
Zoom Image
Fig. 4 Presumed COVID-19-associated pansinusitis with bilateral involvement of the maxillary sinus (white stars), the ethmoidal cells (black star, A) in contrast-enhanced T1w images, and of the sphenoid sinus (B, black star) in T2w images.
Table 1b

Time of occurrence and outcome regarding neurological symptoms.

#

neurological symptoms

start of neurological symptoms

outcome

1

confusion

with other symptoms

death

2

confusion

with other symptoms

asymptomatic

3

temporary loss of consciousness

with other symptoms

asymptomatic

4

Impaired consciousness

during hospitalization

asymptomatic

5

confusion

with other symptoms

asymptomatic

6

right paresthesia

weeks later

asymptomatic

7

Impaired consciousness

during hospitalization

soporose

8

headache

with other symptoms

asymptomatic

9

Impaired consciousness

during hospitalization

death

10

dizziness, sudden hearing loss

weeks later

asymptomatic

11

Impaired consciousness

during hospitalization

death

12

hyposmia and hypogeusia

with other symptoms

asymptomatic


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Discussion

Initial imaging results in a series of 58 patients with severe cases of COVID-19 were published by Helms et al. [6]. Meningeal contrast enhancement was seen in 8 of 13 patients (62 %) and cerebral ischemia in 3 patients (23 %).

Kandemili et al. report on patients with severe cases of COVID-19 in Turkey [7]. Cortical signal changes in FLAIR weighting accompanied by cortical diffusion impairment, leptomeningeal enhancement, or cortical blooming artifacts were seen in 10/27 patients (37 %).

Radmanesh report on 242 patients (of a total of 3661 patients, 6.6 %) with neurological symptoms in New York, who were examined primarily with CT. 13 patients (4.5 %) had acute or subacute ischemic infarct and 11 patients (3.8 %) intracranial hemorrhages. The majority of patients had no specific changes, particularly no meningeal contrast enhancement [8].

The high prevalence of cases of cerebral ischemia occurring in association with COVID-19 is noteworthy. Case series from France [9], the USA [10], and Italy [11] show a significantly worse clinical neurological outcome and a greater mortality rate in patients with COVID-19 and cerebral ischemia compared to patients without COVID-19 and cerebral ischemia. In addition, COVID-19 was identified as an independent risk factor for cerebral ischemia [12].

As in other collectives, the frequency of neurological symptoms (approx. 18 %) in our cohort is lower than that reported by Mao et al. One reason for this is that we only included patients with neurological symptoms resulting in cerebral imaging. Two patients in our cohort had cerebral ischemia (approx. 17 %) and one patient (approx. 8 %) had intracranial hemorrhages. However, most patients did not have any acute pathologies which corresponds with the literature.

Various damage mechanisms of the CNS have been discussed. 1) Direct neuroinvasion by SARS-CoV; 2) Secondary cerebral damage caused by ischemia and bleeding due to possible endothelial dysfunction and systemic hypercoagulability and possibly due to thromboses of the small cerebral veins caused by cerebral hemorrhages [13]. 3) Indirect damage due to cytokines and post-infection antibodies [14]. To date, it has not been possible to clearly define the damage pattern and the clarify which mechanisms are most prevalent and how frequently they occur. Neuropathological correlation studies are necessary to answer these questions and to identify a causality between the infection and damage patterns [15].

We present the first German case series from a minimally affected region. Our study includes COVID-19 patients with mild, moderate, and severe disease courses who underwent neuroradiological imaging and includes post-infection data and data regarding newly occurring neurological symptoms. In summary, these findings are currently still heterogeneous and nonspecific. Further long-term studies are needed to detect potential residual and late effects of COVID-19. In this regard, we initiated a population-based cohort study www.covidom.de.


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Conflict of Interest

The authors declare that they have no conflict of interest.


Correspondence

Herr Dr. Ulf Jensen-Kondering
Department of Radiology and Neuroradiology, University Hospital Schleswig-Holstein, Campus Kiel
Arnold-Heller-Str. 3, Haus 41
24116 Kiel
Germany   
Phone: +49/4 31/5 97 48 06   
Fax: +49/4 31/5 97 49 13   

Publication History

Received: 18 July 2020

Accepted: 04 September 2020

Publication Date:
19 November 2020 (online)

© 2020. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany


Zoom Image
Fig. 1 Presumed central pontine myelinolysis in a patient with severe and prolonged COVID-19 course. Hyperintense central pontine lesion in T2w images. A with corresponding diffusion impairment B but without contrast enhancement C after contrast agent administration. While hospitalized, the patient showed no hyponatremia and no relevant hypernatremia but now requires dialysis. There were no laboratory findings prior to the patient being transferred to us. Lumbar puncture was not performed.
Zoom Image
Fig. 2 Cerebral ischemia pattern. Bilateral hemodynamic stroke along the inner boundary zone A. Acute left cerebellar infarction in the territory of the inferior posterior cerebellar artery B. Subacute hemorrhagic infarction in the territory of the right posterior cerebral artery C. Subacute infarction of the left thalamus with contrast enhancement D and also small left parietal infarcts.
Zoom Image
Fig. 3 Right cerebellar parenchymal hemorrhage (dark arrow) and bifrontal subarachnoid hemorrhages (light arrows) in a susceptibility-weighted sequence and additional axial FLAIR B, C to show the extraaxial localisation of the bifrontal hemorrhages (light arrows). Prior to acquisition of the MRI scan, anticoagulation therapy was performed to treat a pulmonary artery embolism with low-molecular heparin (tinzaparin) administered subcutaneously followed by unfractionated heparin with a target PTT of 70–80 s and then rivaroxaban and clopidogrel.
Zoom Image
Fig. 4 Presumed COVID-19-associated pansinusitis with bilateral involvement of the maxillary sinus (white stars), the ethmoidal cells (black star, A) in contrast-enhanced T1w images, and of the sphenoid sinus (B, black star) in T2w images.
Zoom Image
Abb. 1 Mutmaßliche zentrale pontine Myelinolyse bei einem Patienten mit schwerem und prolongiertem Verlauf von COVID-19. Zentropontine hyperintense Läsion in der T2-Wichtung A mit korrespondierender Diffusionsstörung B, aber ohne Schrankenstörung C nach Kontrastmittelgabe. Der Patient zeigte während des Aufenthalts bei uns allerdings keine Hyponatriämie und keine relevante Hypernatriämie, zwischenzeitlich war der Patient dialysepflichtig. Laborbefunde vor der Verlegung zu uns lagen nicht vor, eine Lumbalpunktion erfolgte nicht.
Zoom Image
Abb. 2 Muster der zerebralen Ischämien. Bilaterale hämodynamische Infarkte entlang der inneren Grenzzone A. Akuter linkszerebellärer Infarkt im Stromgebiet der A. cerebelli posterior inferior B. Subakuter hämorrhagisierter Infarkt im Stromgebiet der A. cerebri posterior rechts C. Subakuter schrankengestörter Infarkt des Thalamus links D und kleine Infarkte auch links parietal.
Zoom Image
Abb. 3 Rechtszerebelläre parenchymale Einblutung (dunkler Pfeil) und bifrontale subarachnoidale Einblutungen (helle Pfeile) in einer suszeptibilitätsgewichteten Sequenz, zur Verdeutlichung der extraaxialen Lage der bifrontalen Einblutungen (helle Pfeile) zusätzliche axiale FLAIR B, C. Vor der Erstellung des MRT erfolgte die Antikoagulation zur Behandlung einer Lungenarterienembolie zunächst mit einem niedermolekularen Heparin (Tinzaparin) subkutan, anschließend mit einem unfraktionierten Heparin mit einer Ziel-PTT von 70–80 s und dann mit Rivaroxaban und zusätzlichem Clopidogrel.
Zoom Image
Abb. 4 Mutmaßliche COVID-19-assoziierte Pansinusitis mit Beteiligung des Sinus maxillaris beidseits (weiße Sterne), der Ethmoidalzellen (schwarzer Stern, A) in der kontrastmittelverstärkten T1-Wichtung und des Sinus sphenoidalis (B, schwarzer Stern) in der T2-Wichtung.