Endovascular recanalisation therapy for prolonged basilar artery occlusion based on clinical-diffusion MRI mismatch

Objectives

Clinical-diffusion magnetic resonance imaging (MRI) mismatch (CDM) in patients with anterior circulation occlusions is an optional method used to select patients for recanalisation outside the 3-h time window. A similar concept has not been reported with posterior circulation occlusions.

Methods

CDM was defined as a Glasgow Coma Scale (GCS) score <8 with DWI lesions not located in the dorsal pons, midbrain or thalamus at the time of admission. Eligible patients were treated with endovascular recanalisation therapy (ERT). The treatment included intra-arterial rt-PA thrombolysis and angioplasty and stenting performed separately or combined. The recanalisation result was assessed by angiography immediately after the treatment according to the trial reports in the Thrombolysis in Myocardial Infarction Criteria (TIMI). The complications and outcome 3 months later were recorded.

Results

Nine patients with a mean age of 66.6 years were included in the study (7 men and 2 women). The median durations of clinical presentation and coma were 31 h (range 25–53 h) and 6 h (range 2–13 h). The median GCS score at admission was 6 (range 4–7). Occlusions were located in the proximal basilar artery (BA) (n = 2) and the middle BA (n = 7). ERT was successful in 8 patients (TIMI 2, n = 2 and TIMI 3, n = 6) but failed in 1 patient because recanalisation was not possible (TIMI 0). No intracranial haemorrhage or dissections occurred during treatment. The recanalised patients recovered consciousness within 9–27 h after treatment. The median GCS score upon discharge was 14 (range 3–15). Three months later, 6 patients had a good outcome (modified Rankin Score (mRS) 0–2), and 2 patients had a moderate outcome (mRS 3). The patient who did not undergo recanalisation died in the rehabilitation hospital 21 days later.

Conclusions

CDM may be a valid method for selecting patients with prolonged basilar artery occlusion (BAO) who are eligible for recanalisation treatment. ERT was feasible for patients with BAO. A good clinical outcome was achieved with successful recanalisation.     

Effects of regularity on the processing of sound omission in a tone sequence in musicians and non‐musicians

Numerous studies have reported that perceptual grouping affects the pre‐attentive processing of sound omission in a sequence of tones. However, it remains unclear whether or not the perceptual grouping and musical experience affect the attentive processing of sound omission. To this end, we created a sequence of loud (L) and soft (S) tones grouped as ‘LLSLLS…’ and a random sequence of the L and S tones. The omission of the L tones was inserted pseudo‐randomly in the random sequence, and there were two positions at which it was inserted. For within‐group omission, the omission was after the first L tone within the ‘LLS’ pattern. For between‐group omission, the omission was inserted between the patterns. The brain response to the omission in musicians and non‐musicians was measured using magnetoencephalography. During the magnetoencephalography measurement, the subjects' performance in a task to detect the omission was faster in the random sequence than in the group sequence. Source analysis showed that the omission in the random sequence caused greater activity than that in the group sequence. The increase was found in the right inferior parietal lobe in musicians, whereas it was found in the left superior temporal gyrus in non‐musicians. These results suggest that the attentive processing of perceptual grouping might implicate the left superior temporal gyrus or right inferior parietal lobe, depending on musical experience.     

IgG subclass profile among anti‐Glutathione S‐transferase T1 antibodies in post‐transplant de novo immune hepatitis

Although the pathogenic pathways leading to de novo immune hepatitis (IH) are not completely understood, we have shown strong evidences of an antidonor response against Glutathione S‐transferase T1 (GSTT1), an antigen exclusively expressed in the donor liver. The first sign of this process is the production of GSTT1 antibodies that, in 25% of the cases, will precede de novo IH. Because the presence of the antibodies is not sufficient to trigger the disease, we aimed to study GSTT1 IgG subclasses in a group of 18 liver transplant patients, 12 that developed de novo IH and 6 that remained free of disease. Surprisingly, the predominant subclasses were IgG1‐_GSTT1 and IgG4‐_GSTT1. The presence of IgG4‐expressing plasma cells was also investigated in 10 available liver biopsies. Six biopsies coinciding with diagnosis showed a mean value of 32.8 IgG4+ plasma cells/hpf vs. 5.55 in patients without the disease. We have not found a distinctive GSTT1‐IgG profile in patients with de novo IH, but the ratio IgG1‐_GSTT1/IgG4‐_GSTT1 in samples from close to the time of diagnosis seemed to be important. The novel finding of abundant IgG4‐_GSTT1 in liver transplantation is intriguing, but their possible role in pathogenesis of de novo IH remains unknown.     

Mismatch negativity on the cone of confusion

Localization of sounds by the auditory system is based on the analysis of three sources of information: interaural level differences (ILD, caused by an attenuation of the sound as it travels to the more distant ear), interaural time differences (ITD, caused by the additional amount of time it takes for the sound to arrive at the more distant ear), and spectral cues (caused by direction-specific spectral filter properties of the pinnae). Although in a number of psychophysiological studies cortical processes of ITD and ILD analysis were investigated, there is hitherto no evidence on the cortical processing of spectral cues for sound localization. The objective of the present experiment was to test whether it is possible to observe electrophysiological correlates of sound localization based on spectral cues. In an auditory oddball experiment, 80 ms of broadband noise from varying free field locations were presented to inattentive participants. Mismatch negativities (MMNs) were observed for pairs of standards and location deviants located symmetrically with respect to the interaural axis. As interaural time and level differences are identical for such pairs of sounds, the observed MMNs most likely reflect cognitive processes of sound localization utilizing the spectral filter properties of the pinnae. MMN latencies suggest that sound localization based on spectral cues is slower than ITD- or ILD-based localization.     

Decomposition of the ERP late posterior negativity: effects of retrieval and response fluency

Negativity elicited by recognized items over posterior sites--the late posterior negativity (LPN)--has been linked to action monitoring, task "uncertainty," and contextual retrieval. Four recognition tests required retrieval of encoding operations. Task fluency was assumed to increase with each block. The responses assigned to the episodic sources were reversed in Block 3 to reduce response fluency. Dissociable LPNs were identified; the 1200-1900-ms LPN was insensitive to task and response fluency and may reflect the maintenance of a retrieved episode. The 600-1200-ms LPN was sensitive to task fluency and may index the search for episodic information. A response-related LPN was sensitive to response fluency and was consistent with an action monitoring role. The findings confirm that the LPN is functionally heterogeneous, and comprises subcomponents sensitive to retrieval fluency, action monitoring, and postretrieval processing respectively.     

No difference in the occurrence of mismatch repair defects and APC and CTNNB1 genes mutation in a multi-racial colorectal carcinoma patient cohort

BACKGROUND AND AIMS: Colorectal cancers of different subtypes involve different pathogenic pathways like the Wnt and the mutator pathways. In this study, we screened 73 colorectal cancer cases from a multi-racial group for genetic and expression profile defects with the aim of correlating these with patients' clinicopathological characteristics. METHODS: Mutation screening of the entire coding region of APC and exon 3 of CTNNB1, loss of heterozygosity (LOH) of APC, and microsatellite instability (MSI) status were assessed for 44 patients with available paired frozen normal and tumour tissues. In addition, 29 cases with available paraffin embedded tumour blocks were screened for mutation in exon 3 of CTNNB1, the APC mutation cluster region (codon 1286-1513), and hMLH1, hMSH2, hMSH6 protein expressions by immunohistochemistry method. RESULTS: In our study, 15/73 cases showed APC mutations (20.5%), 1/73 cases had CTNNB1 mutation (1.4%), 5/32 cases had APC LOH (15.6%), and 16/70 (22.9%) cases revealed at least some form of mismatch repair (MMR) defect. Tumour grade (poor differentiation) was found to correlate significantly with right-sided tumour and mucinous histology (p = 0.01879 and 0.00320, respectively). Patients of younger age (below 45 years) more often had tumours of mucinous histology (p = 0.00014), while patients of older age (above 75 years) more often had tumours on the right side of the colon (p = 0.02448). Tumours of the mucinous histology subtype often had MMR defects (p = 0.02686). There was no difference in the occurrence of APC and CTNNB1 mutations and MMR defects found within our multi-racial colorectal cancer patient cohort. CONCLUSION: Our findings support the notion that racial factor may not be related to the occurrence of MMR defects and APC and CTNNB1 mutations in our multi-racial patient cohort.     

Constitutive deficiency in DNA mismatch repair: is it time for Lynch III?

Hereditary non-polyposis colorectal cancer (HNPCC), also known as Lynch syndrome types I and II, and the related subtypes Turcot and Muir-Torre syndrome, have all been associated with inheritance of germ line mutations in the DNA mismatch repair (MMR) genes. Fifty individuals have recently been identified with an early onset of a different spectrum of cancers associated with inheritance of two MMR mutations--resulting either in a constitutive loss of MMR function, or greatly impaired MMR function. In contrast to Lynch I and II individuals, individuals with inheritance of homozygous or compound heterozygous mutations in the MMR genes that result in a complete lack of protein, present with hematological and brain malignancies in the first decade of life. Biallelic mutations with compromised but residual protein function present with a broader spectrum of cancers (brain, hematological or gastrointestinal) in the second to fourth decades of life. We propose that inheritance of two MMR mutations in an individual and the unique tumor spectrum that occurs with an early onset should be defined separately from Lynch syndrome I and II, or the subtypes Turcot and Muir-Torre. We suggest Lynch III as an appropriate name for identifying individuals with constitutively compromised MMR associated with biallelic mutations.     

The effect of stimulus probability on the somatosensory mismatch field

We investigated the effect of deviant stimulus probability on the somatosensory magnetic mismatch negativity (MMNm) using an electrical two-point stimulation. First, we determined the discrimination threshold (DT) of the two-point distance. We applied standard stimuli at a distance that subjects felt as one point and deviant stimuli at a distance that subjects definitely felt as two points. We used three deviant stimulus probabilities, 10, 30, and 50%. The components peaking around 30–70 ms (first component) and 150–250 ms (fourth component) following deviant stimuli were significantly larger than those following standard stimuli in 10% condition, but not in 30 or 50% condition. The equivalent current dipole (ECD) was located in the contralateral primary somatosensory cortex (cSI) for the first component, and in the cSI and in the contralateral secondary somatosensory cortex (cSII) for the fourth component. The peak amplitude of the MMNm decreased as the probability of the deviant stimulus increased. The Somatosensory MMNm was affected by deviant stimulus probability similar to an auditory mismatch negativity (MMN).