Scattered cerebral infarction in the corona radiata predicts worse outcomes.

OBJECTIVES: Intracranial branch atheromatous disease often results in progressive motor deficits in the lenticulostriate arteries (LSA). In some patients with LSA infarction, magnetic resonance imaging (MRI) revealed single lesions at the LSA origin from the middle cerebral artery spreading in a scattered manner toward the distal area. This study aimed to elucidate the clinical characteristics of such cases. MATERIALS AND METHODS: This was a single-center, retrospective study comprising 1,840 consecutive patients admitted to the Ina Central Hospital, Japan. Two neurologists selected patients with LSA infarctions on the basis of MRI data. Patients with a single mass of infarct lesion from the origin were classified as the single group, whereas patients with infarct lesions as a single mass at LSA origin but divided and independent as the infarct area extended distally were classified as the scattered group. We compared the clinical characteristics and outcomes in these groups. RESULTS: The single and scattered groups included 119 and 35 patients, respectively. We defined worsening as an increase of one point or more on the National Institute of Health Stroke Scale. Univariate analysis demonstrated that patients in the scattered group showed significantly more worsening after hospitalization compared with those in the single group (48.6% vs. 28.6%; p < .05). Moreover, this can easily lead to increased disease severity (p < .016). In a multivariate analysis, group (odds ratio, 2.5 [95% CI, 1.11-5.74], p < .03) was an independent predictor of symptom worsening. CONCLUSIONS: Scattered infarction in the corona radiata is an aggravating factor leading to worse outcomes.

Visualization of thrombus using iterative reconstruction and maximum intensity projection of thin-slice CT images.

OBJECTIVE: Iterative reconstruction (IR) is a noise reduction method that facilitates the synthesis of maximum intensity projection (MIP) from a larger number of slices while maintaining resolution. The present study aimed to analyze whether CT evaluation using IR and MIP is ideal for thrombus evaluation of large vessel occlusions in patients with acute ischemic stroke. METHODS: Three types of images for each patient were reconstructed and categorized into three groups: the "conventional group," evaluated using 0.5-mm slice CT, the "MIP group," evaluated using 0.5-mm slice CT processed with MIP, and the "IR + MIP group," evaluated with 0.5-mm slice CT processed with IR and MIP. Noise and image quality were evaluated with noise standard deviation (Noise SD) and contrast-to-noise ratio (CNR). Three experts evaluated the thrombus edge coordinates, made a visual assessment, and compared the data with the digital subtraction angiography (DSA) of the mechanical thrombectomy. RESULTS: Twenty-nine patients with cerebral infarction having large vessel occlusion were included in this study. The IR + MIP group had a lower Noise SD and a statistically higher CNR, leading to more favorable image evaluations. The thrombus assessment showed no inter-rater variability in thrombus edge identification, and the visual assessment and comparison with DSA were statistically better in the IR + MIP group. CONCLUSIONS: IR reduces noise and improves resolution. MIP in combination with IR facilitates visualization of thrombus.

Prevalence of Fabry disease and GLA c.196G>C variant in Japanese stroke patients.

Fabry disease is an important underlying disease in young cryptogenic stroke patients. However, little is known regarding the frequency of Fabry disease in the general stroke population, especially in elderly patients. A total of 588 stroke patients (61.7% men; average age 74.1±12.5 years) were enrolled in this prospective study. Blood samples were obtained to produce blood spots to determine α-galactosidase A (α-GalA) activity and for GLA gene analysis. One 65-year-old female patient had a known GLA gene mutation, c.2T>C (p.M1T), causing Fabry disease. Five male patients and two female patients had GLA c.196G>C (p.E66Q) variant, which is not associated with the full clinical manifestations of Fabry disease. The allele frequency of GLA c.196G>C was significantly higher in male patients with small-vessel occlusion (odds ratio 3.95, P=0.048) and non-cardioembolism (odds ratio 4.08, P=0.012) than that in the general Japanese population. Fabry disease is rare in the general Japanese stroke population. However, screening identified one elderly female patient with Fabry disease. GLA c.196G>C variant is a genetic risk factor for cerebral small-vessel occlusion and non-cardioembolism in Japanese males but not in females.

Pathological, biochemical, and biophysical characteristics of the transthyretin variant Y114H (p.Y134H) explain its very mild clinical phenotype.

Transthyretin (TTR) is a homotetrameric protein that must misfold in order to form amyloid fibrils. Misfolding includes rate limiting tetramer dissociation, followed by fast tertiary structural changes of the monomer that enable aggregation. Hereditary ATTR amyloidosis is an autosomal dominant genetic disorder with systemic deposition of amyloid fibrils induced by TTR gene mutation. We identified a rare Y114H (p.Y134H) TTR variant in a Japanese patient presenting with late-onset, very mild clinical course. The patient had an extremely low serum variant TTR concentration (18% of total TTR), whereas the composition of variant TTR was 55% in amyloid fibrils in tenosynovial tissues obtained at carpal tunnel release surgery. The amyloid fibril deposits in the ATTR Y114H patient had an altered structure compared with that in wild-type ATTR patients, as determined by luminescent conjugated poly/oligo-thiophene fluorescence spectroscopy. Biophysical studies using recombinant protein showed that Y114H TTR was markedly destabilized both thermodynamically and kinetically and was highly amyloidogenic in vitro. These data suggest that extremely low serum variant Y114H TTR concentration, probably due to endoplasmic reticulum-associated degradation of unstable variant TTR protein, protected this patient from severe amyloidosis, as self-assembly of the amyloidogenic intermediate is a concentration-dependent process.

Cavernous Sinus Swelling and Abducens Nerve Paresis Due to Intracranial Hypotension.

The most common neurological symptom of spontaneous intracranial hypotension (SIH) is abducens nerve paresis, and the precise pathophysiology is unclear. The accepted explanation is traction on the cranial nerves caused by the downward displacement of the cranial content. We herein report magnetic resonance imaging of SIH that can explain the mechanism underlying abducens nerve paresis. The cavernous sinuses were particularly thickened compared with the surrounding dura. This phenomenon can be explained by venous swelling, which can occur after leakage of cerebrospinal fluid in a closed cavity. This swelling pushes the abducens nerve up, which then causes abducens nerve paresis.

Thyroid hormone decreasing after mechanical thrombectomy for cerebral infarction.

OBJECTIVE: Mechanical thrombectomy (MT) is an established treatment for large vessel occlusion in patients with cerebral infarction. The use of iodine contrast agent decreases thyroid hormone levels via the Wolff-Chaikoff effect. Low triiodothyronine (T3) syndrome caused due to severe illness status can contribute to decreased levels of thyroid hormones. Reportedly, a low T3 level is associated with poor prognosis in patients with cerebral infarction. This study aimed to clarify the changes in thyroid hormone levels in the acute phase after MT and the effects of the iodine contrast agent on these hormones. METHODS: This was a single-center, prospective, and single-arm trial. Thyroid stimulating hormone (TSH), free T3 (FT3), and free T4 (FT4) levels were tested on admission and 24 h postoperatively in patients who were approved for MT. RESULTS: A total of 37 patients were screened during the study period and 31 patients were enrolled in this study. Significant decreases were observed in TSH (P < 0.001) and FT3 (P < 0.001) levels 24 h after MT. Moreover, there was a correlation between the decrease in ratio of change in FT3 levels and the amount of iodine contrast agent used per body surface area (r = 0.43, P = 0.019), while no such correlations were detected for TSH and FT4. CONCLUSION: We demonstrated that TSH and FT3 levels decreased in the acute phase after MT and that FT3 levels were associated with the amount of iodine contrast agent used.

Persistent Working Memory Impairment Associated with Cerebral Infarction in the Anterior Cingulate Cortex: A Case Report and a Literature Review.

A 52-year-old man experienced sudden-onset global amnesia and left limb ataxia. An embolism of the right anterior cerebral artery resulted in anterior cingulate cortex (ACC) infarction, and working memory dysfunction persisted. The ACC, prefrontal cortex, and bilateral superior parietal lobule exhibited decreased activity on single-photon emission computed tomography (SPECT). The ACC handles working memory formation and is essential for the executive function. The areas showing a decreased activity on SPECT were responsible for the working memory, which corresponded to the observed symptoms. This is the first case in which limited ACC infarction resulted in permanent working memory dysfunction, and SPECT revealed the decreasing working memory in the associated region.

Cerebral hemorrhage in Fabry's disease.

Fabry's disease is an X-linked lysosomal storage disorder resulting from alpha-galactosidase A deficiency. Although ischemic stroke is recognized as an important manifestation of Fabry's disease, hemorrhagic stroke is considered to be rare. Here, we report our recent clinical experience with three hemizygous male patients with Fabry's disease who developed cerebral hemorrhage. One patient had classic type Fabry's disease with p.Ala37Val mutation and others had cerebrovascular variant with p.Glu66Gln mutation. Degeneration of the cerebral small arteries secondary to deposition of glycosphingolipids and aging, in addition to hypertension and antiplatelet/anticoagulant agents, are considered to be contributing factors for hemorrhage. Fabry's disease is frequently associated with not only ischemic but also hemorrhagic stroke, especially in elderly patients.

A novel nonsense mutation in the TITF-1 gene in a Japanese family with benign hereditary chorea.

A Japanese family with a novel nonsense mutation in the TITF-1 gene (p.Y98X) is described. The proband showed severe generalized chorea, delayed motor development, subnormal intelligence, congenital hypothyroidism, bronchial asthma, and a history of pulmonary infection, all of which are characteristic features of Brain-Thyroid-Lung syndrome. On the other hand, her brother and mother showed a mild benign hereditary chorea (BHC) phenotype with congenital hypothyroidism. Intrafamilial phenotypic variation is common in BHC/Brain-Thyroid-Lung syndrome and suggests the existence of other genetic or environmental factors regulating TITF-1 function. Although choreic movement in BHC/Brain-Thyroid-Lung syndrome is recognized as non-progressive, the proband showed re-exacerbation of choreic movement at puberty. The dopamine agonist, ropinirole hydrochloride, reduced her choreic movements, suggesting that levodopa and/or dopamine agonists may compensate for underdeveloped dopaminergic pathways in this disorder.