The authors have declared that no competing interests exist.
Conceived and designed the experiments: AF CG. Performed the experiments: AF HUK HW. Analyzed the data: AF HUK JG HW CG. Wrote the paper: AF HUK JG HW CG.
Crossed cerebellar diaschisis (CCD) is a state of neural depression caused by loss of connections to injured neural structures remote from the cerebellum usually evaluated by positron emission tomography. Recently it has been shown that dynamic susceptibility contrast perfusion weighted MRI (PWI) may also be feasible to detect the phenomenon. In this study we aimed to assess the frequency of CCD on PWI in patients with acute thalamic infarction.
From a MRI report database we identified patients with acute isolated thalamic infarction. Contralateral cerebellar hypoperfusion was identified by inspection of time to peak (TTP) maps and evaluated quantitatively on TTP, mean transit time (MTT), cerebral blood flow and volume (CBF, CBV) maps. A competing cerebellar pathology or an underlying vascular pathology were excluded.
A total of 39 patients was included. Common symptoms were hemiparesis (53.8%), hemihypaesthesia (38.5%), dysarthria (30.8%), aphasia (17.9%), and ataxia (15.4%). In 9 patients (23.1%) PWI showed hypoperfusion in the contralateral cerebellar hemisphere. All of these had lesions in the territory of the tuberothalamic, paramedian, or inferolateral arteries. Dysarthria was observed more frequently in patients with CCD (6/9 vs. 6/30; OR 8.00; 95%CI 1.54–41.64, p = 0.01). In patients with CCD, the median ischemic lesion volume on DWI (0.91 cm3, IQR 0.49–1.54 cm3) was larger compared to patients with unremarkable PWI (0.51 cm3, IQR 0.32–0.74, p = 0.05). The most pronounced changes were found in CBF (0.94±0.11) and MTT (1.06±0.13) signal ratios, followed by TTP (1.05±0.02).
Multimodal MRI demonstrates CCD in about 20% of acute isolated thalamic infarction patients. Lesion size seems to be a relevant factor in its pathophysiology.
At the beginning of the 20th century the term “diaschisis” was introduced by the russian neurologist and neuropathologist Constantin von Monakow to describe a state of neural depression in the brain caused by loss of connections to injured neural structures remote from the affected brain area
In particular in the thalamus with its numerous connections to different sensory pathways, the motor system including basal ganglia and brainstem, as well as the limbic system, lesions may give rise to signs and symptoms like aphasia, hemineglect, or ataxia among others which are thought to represent a cortical dysfunction by impaired thalamocortical connections
Until today there are no studies systematically evaluating the presence and extent of CCD in acute isolated thalamic infarctions. We therefore aimed to assess the frequency of CCD on perfusion-weighted MRI (PWI) and the degree of hemodynamic alterations in a retrospective series of patients with acute isolated thalamic infarction collected over 9 years who were evaluated by a standard stroke MRI protocol including diffusion-weighted MRI (DWI) and dynamic susceptibility contrast PWI. Furthermore, we sought to compare the clinical presentation in patients with and without CCD.
This study was approved by the local institutional review board (Medizinische Ethikkommission II der Medizinischen Fakultät Mannheim) and did not require consent. Consent was not required by our IRB for this de-identified database (Perfusion-weighted imaging in Isolated Thalamic Infarction - PITI) due to the retrospective nature of the study and the lack of patient interaction. From a prospectively maintained MRI report database (Syngo Data Manager – SDM), we identified 698 patients with suspected acute ischemic stroke who underwent a standard stroke MRI protocol including PWI (2005–2013). Among these, 46 (6.6%) had an acute isolated ischemic infarction in the thalamus. Of these, 2 patients were excluded due to cerebellar hypoperfusion restricted to the territory of the posterior inferior cerebellar artery, 3 patients due to occlusion of the posterior cerebral artery and marked hypoperfusion, and finally, 2 patients because of suboptimal MRI quality due to motion artifacts. The remaining 39 (5.6%) patients formed the study population and were retrospectively studied with regard to demographic details and clinical symptoms as abstracted from the case records as well as MRI findings. Standardized clinical work-up included assessment of cardiovascular risk factors, extra- and transcranial Doppler−/duplex sonography, 24-hour electrocardiogram monitoring and transthoracic or transesophageal echocardiography as well as laboratory tests according to stroke unit standard requirements in Germany
Magnetic resonance imaging was performed on a 1.5-T MR system (Magnetom Avanto or Sonata, Siemens Medical Systems, Erlangen, Germany) at admission. A standardized protocol was used in all patients including (1) transverse, coronal and sagittal localizing sequences followed by transverse oblique contiguous images aligned with the inferior borders of the corpus callosum (applied on sequences 2–5 and 7); (2) T1-weighted spin echo sequence; (3) T2-weighted turbo spin echo sequence; (4) isotropic diffusion-weighted echo-planar spin-echo sequence (DWI); (5) fluid attenuated inversion recovery (FLAIR) sequence; (6) a time-of-flight MRA; and (7) PWI following the first pass of contrast bolus through the brain. Perfusion-weighted imaging was acquired using a gradient-echo echo planar imaging sequence. The contrast agent gadoteric acid (Dotarem, Guerbet, Aulnay-sous-Bois, France) was bolus injected by a power injector (Spectris MR injection system, Medrad, Volkach, Germany) with a dose of 0.1 mmol/kg of body weight at a rate of 4 ml/sec.
The postprocessing of the perfusion-weighted raw images was performed by a specific software, Signal Processing In NMR (SPIN, The MRI Institute for Biomedial Research, Detroit, USA)
Acute ischemic lesion size was measured on DWI by manually delineated region of interest (ROI), summation of these areas in cm2 on each section and multiplication by the interslice spacing, to determine the volume in cm3 by use of OsiriX, a multidimensional image navigation and display software
To obtain information about hemodynamic alterations, calculated time to peak (TTP) images demonstrating the delay of the contrast agent arrival in the brain parenchyma were used for visual analysis. Cases with cerebellar hypoperfusion contralateral to the thalamic infarction not confined to a specific vascular territory were identified by visual inspection of the TTP maps. For the diagnosis of crossed cerebellar diaschisis a decrease in perfusion on PWI on the basis of increased TTP of the contralateral cerebellar hemisphere was mandatory. In addition, the generated perfusion maps were quantitatively assessed by use of SPIN: a ROI encompassing the complete hypoperfused cerebellar hemisphere was placed on the generated maps (CBF, CBV) as well as mirrored to the contralateral unaffected hemisphere. Finally, ratios between the physiological estimates of the affected hemisphere and the contralateral mirror ROI were then determined.
A competing cerebellar pathology or a possible underlying abnormality of the vertebrobasilar system was excluded on DWI, T1- and T2-weighted images, and MR angiography respectively.
All statistical analyses were performed using Statistical Product and Service Solutions (SPSS) statistics for Windows (Release 17.0; SPSS, Chicago, IL, USA). Descriptive data was analyzed using either the Mann-Whitney
In the final analysis 39 of 698 (5.6%) patients were included. The median age was 72 years (IQR 63–79 years); 20 (51.3%) patients were male, and 19 (48.7%) patients were female. Most commonly observed clinical symptoms were hemiparesis (53.8%), hemihypaesthesia (38.5%), dysarthria (30.8%), aphasia (17.9%), ataxia (15.4%), oculomotor dysfunction (12.8%), and altered vigilance (10.3%) whereas other symptoms like disorientation, apraxia or vertigo were observed only occasionally. For details see
All, n = 39 | CCD, n = 9 | Normal PWI, n = 30 | OR; 95%CI | p | |
72 (63–79) | 75 (67.5–81.5) | 72 (57–76.25) | 0.13 | ||
20 (41.3) | 3 (33.3) | 17 (56.7) | 0.38; 0.08–1.83 | 0.22 | |
325 (241–480) | 343 (106–420) | 321 (244.75–480) | 0.54 | ||
0.65 (0.35–0.91) | 0.91 (0.49–1.54) | 0.51 (0.32–0.74) | 0.05 | ||
5 (12.8) | 3 (33.3) | 2 (3.3) | 0.16 | ||
17 (43.6) | 4 (44.4) | 13 (43.3) | |||
16 (41.0) | 2 (22.2) | 14 (46.7) | |||
1 (2.3) | 0 | 1 (3.3) | |||
12 (30.8) | 6 (66.7) | 6 (20.0) | 8.00; 1.54–41.64 | ||
21 (53.8) | 4 (44.4) | 17 (56.7) | 0.61; 0.14–2.74 | 0.71 | |
15 (38.5) | 2 (22.2) | 13 (43.3) | 0.37; 0.07–2.11 | 0.44 | |
6 (15.4) | 2 (22.2) | 4 (13.3) | 1.86; 0.28–12.31 | 0.61 |
All patients underwent MRI within a median time of 325 minutes (IQR 241–480 minutes) after symptom onset. Diffusion weighted imaging demonstrated an acute ischemic infarction in the thalamus in the territory of the tuberothalamic artery in 5 (12.8%), the paramedian artery in 17 (43.6%), the inferolateral arteries in 16 (41.0%) patients and the posterior choroidal arteries in 1 (2.6%) patient. The right side was affected in 15 (38.5%), and the left side in 24 (61.5%) patients. The ischemic lesions had a median volume 0.65 cm3 (IQR 0.35–0.91 cm3).
In 9 patients (23.1%) PWI showed a hypoperfusion in the contralateral cerebellar hemisphere not confined to a specific vascular territory. For examples see
1. A 75-year-old female patient with reduced vigilance, dysarthria, and right-sided hemihypaesthesia:
Lesion size on DWI did not correlate with signal ratios of TTP (rS = 0.30, p = 0.43), MTT (rS = 0.22, p = 0.58), CBF (rS = −0.22, p = 0.58), nor CBV (rS = 0.25, p = 0.52).
With regard to the clinical presentation no significant differences were observed except for a higher rate of dysarthria in patients with CCD (p = 0.01). Patients with crossed cerebellar diaschisis showed a trend towards a larger median volume of the acute ischemic lesion on DWI in comparison to patients with unremarkable PWI (p = 0.05). For details see
Crossed cerebellar diaschisis is a well-defined phenomenon probably caused by interruption of cortico-ponto-cerebellar fibers
In the present study, we were able to demonstrate CCD in about 20% of patients with isolated thalamic infarctions. This frequency is in line with a previously published study on detection of CCD with perfusion MRI in supratentorial infarction reporting a rate of 15.61%
The observation of CCD in acute isolated thalamic infarctions underscores that the phenomenon may be present even in small ischemic lesions and not exclusively in larger territorial infarctions. While CCD has been observed predominantly in patients with large infarctions in the middle cerebral artery territory
On the other hand, this finding demonstrates that in particular thalamic lesions may be prone to CCD since the thalamus is an important relay for afferent connections from cerebellar nuclei to the cerebral cortex
With regard to the clinical presentation, only dysarthria was observed more frequently in patients with CCD. However, although cerebellar lesions may cause dysarthria, this is not a characteristic finding. In particular thalamic infarctions may be the cause of dysarthria and consequently, we cannot prove a relation of this symptom to CCD.
The present study has some limitations. First, this is a retrospective case series of moderate size including 9 cases with CCD. Second, only a subset of patients with CCD underwent follow-up MRI and of these only one patient had follow-up PWI. Thus, we cannot draw any conclusions about the evolution of perfusion abnormalities in CCD with time. Third, compared to PET perfusion MRI techniques have a lower sensitivity to depict subtle hemodynamic alterations and as a consequence, some cases of CCD might have been missed. Another limitation of perfusion MRI is the restricted spatial resolution and susceptibility to bone artifacts especially in the posterior fossa.
In conclusion, multimodal MRI including DWI and PWI detects CCD in acute isolated thalamic in about 20% of patients. While previous studies demonstrated mainly a relation of CCD to large supratentorial infarction or hemorrhage, the results of our study suggest that CCD is a frequent finding in acute isolated thalamic infarctions. Furthermore, we could demonstrate that ischemic lesion size may be a relevant factor in the pathophysiology of CCD.