Recurrent Lobar Hemorrhages and Multiple Cortical Superficial Siderosis in a Patient of Alzheimer's Disease With Homozygous APOE ε2 Allele Presenting Hypobetalipoproteinemia and Pathological Findings of 18F-THK5351 Positron Emission Tomography: A Case Report.

In Alzheimer's disease, the apolipoprotein E gene (APOE) ε2 allele is a protective genetic factor, whereas the APOE ε4 allele is a genetic risk factor. However, both the APOE ε2 and the APOE ε4 alleles are genetic risk factors for lobar intracerebral hemorrhage. The reasons for the high prevalence of lobar intracerebral hemorrhage and the low prevalence of Alzheimer's disease with the APOE ε2 allele remains unknown. Here, we describe the case of a 79-year-old Japanese female with Alzheimer's disease, homozygous for the APOE ε2 allele. This patient presented with recurrent lobar hemorrhages and multiple cortical superficial siderosis. The findings on the 11C-labeled Pittsburgh Compound B-positron emission tomography (PET) were characteristic of Alzheimer's disease. 18F-THK5351 PET revealed that the accumulation of 18F-THK 5351 in the right pyramidal tract at the pontine level, the cerebral peduncle of the midbrain, and the internal capsule, reflecting the lesions of the previous lobar intracerebral hemorrhage in the right frontal lobe. Moreover, 18F-THK5351 accumulated in the bilateral globus pallidum, amygdala, caudate nuclei, and the substantia nigra of the midbrain, which were probably off-target reaction, by binding to monoamine oxidase B (MAO-B). 18F-THK5351 were also detected in the periphery of prior lobar hemorrhages and a cortical subarachnoid hemorrhage, as well as in some, but not all, areas affected by cortical siderosis. Besides, 18F-THK5351 retentions were observed in the bilateral medial temporal cortices and several cortical areas without cerebral amyloid angiopathy or prior hemorrhages, possibly where tau might accumulate. This is the first report of a patient with Alzheimer's disease, carrying homozygous APOE ε2 allele and presenting with recurrent lobar hemorrhages, multiple cortical superficial siderosis, and immunohistochemically vascular amyloid ß. The 18F-THK5351 PET findings suggested MAO-B concentrated regions, astroglial activation, Waller degeneration of the pyramidal tract, neuroinflammation due to CAA related hemorrhages, and possible tau accumulation.

Cerebral Microbleeds, Cerebrospinal Fluid, and Neuroimaging Markers in Clinical Subtypes of Alzheimer's Disease.

Lobar cerebral microbleeds (CMBs) in Alzheimer's disease (AD) are associated with cerebral amyloid angiopathy (CAA) due to vascular amyloid beta (Aß) deposits. However, the relationship between lobar CMBs and clinical subtypes of AD remains unknown. Here, we enrolled patients with early- and late-onset amnestic dominant AD, logopenic variant of primary progressive aphasia (lvPPA) and posterior cortical atrophy (PCA) who were compatible with the AD criteria. We then examined the levels of cerebrospinal fluid (CSF) biomarkers [Aß1-42, Aß1-40, Aß1-38, phosphorylated tau 181 (P-Tau), total tau (T-Tau), neurofilament light chain (NFL), and chitinase 3-like 1 protein (YKL-40)], analyzed the number and localization of CMBs, and measured the cerebral blood flow (CBF) volume by 99mTc-ethyl cysteinate dimer single photon emission computerized tomography (99mTc ECD-SPECT), as well as the mean cortical standard uptake value ratio by 11C-labeled Pittsburgh Compound B-positron emission tomography (11C PiB-PET). Lobar CMBs in lvPPA were distributed in the temporal, frontal, and parietal lobes with the left side predominance, while the CBF volume in lvPPA significantly decreased in the left temporal area, where the number of lobar CMBs and the CBF volumes showed a significant inversely correlation. The CSF levels of NFL in lvPPA were significantly higher compared to the other AD subtypes and non-demented subjects. The numbers of lobar CMBs significantly increased the CSF levels of NFL in the total AD patients, additionally, among AD subtypes, the CSF levels of NFL in lvPPA predominantly were higher by increasing number of lobar CMBs. On the other hand, the CSF levels of Aß1-38, Aß1-40, Aß1-42, P-Tau, and T-Tau were lower by increasing number of lobar CMBs in the total AD patients. These findings may suggest that aberrant brain hypoperfusion in lvPPA was derived from the brain atrophy due to neurodegeneration, and possibly may involve the aberrant microcirculation causing by lobar CMBs and cerebrovascular injuries, with the left side dominance, consequently leading to a clinical phenotype of logopenic variant.

Recovery process and prognosis of aphasic patients with left putaminal hemorrhage: relationship between hematoma type and language modalities.

To elucidate the precise recovery process and prognosis of language functions in aphasic patients with left putaminal hemorrhage, we investigated 48 aphasic patients classified into 4 groups according to the location and extent of hematoma. The hematoma extended to the corona radiata in all patients, extracapsular in type I (12 cases), to the anterior limb in type II (10 cases), to the posterior limb in type III (12 cases), and to both limbs in type IV (14 cases). The Standard Language Test for Aphasia was performed at 1 month, 3 months, and 6 months after the attack. The type II, III, and IV patients were divided into 2 groups, with and without ventricular rupture of the hemorrhage. At 3 and 6 months after the attack, the type I, II, and III patients showed significant improvement (P < .05) in all language modalities compared with the type IV patients. Most improvement in language modalities occurred in the first 3 months. The evaluation of patients with ventricular rupture after 6 months revealed poor recovery (P < .05) in oral commands, visual commands, confrontation naming, sentence repetition, narratives, verbal fluency, and writing in type II and III patients. In type IV patients, this evaluation showed poor recovery (P < .05) only in oral and written naming (kanji words). No significant difference in prognostic outcome was observed between the surgical treatment group and the nonsurgical treatment group. The classification of hemorrhage may be useful in predicting the outcome of aphasia with putaminal hemorrhage and in guiding clinicians in providing effective instructions to patients and their relatives.

Analysis of five cases with neurogenic stuttering following brain injury in the basal ganglia.

UNLABELLED: This study examined stuttering patterns in five patients with basal ganglia injury. None of the patients had a history of developmental stuttering. Four patients were right-handed; one patient was ambidextrous. Stuttering tests administered to patients assessed sentence repetition, reading aloud, explanations of a comic strip, and conversation. Accessory behaviors such as facial grimaces, associated movements of the limbs, and avoidance behaviors were observed. The results of this study differ from those of previous studies of neurogenic stuttering in several respects: (1) blocks were frequently observed. (2) Adaptation was observed. (3) Almost all stuttering occurred at the initiation of words. (4) Across patients, stuttering frequency did not vary in a consistent manner with speaking task. New speech characteristics for neurogenic stuttering without aphasia following injury to the basal ganglia are described. EDUCATIONAL OBJECTIVES: After reading this text, the reader will be able to: (1) provide characteristics of neurogenic stuttering after the basal ganglia in patients without aphasia; (2) discuss the difference of the features and characteristics of stuttering between previously reported patients and present patients.

Stuttering after right cerebellar infarction: a case study.

UNLABELLED: We report a male patient with neurogenic stuttering after cerebellar infarction. He had suffered from frontal and thalamus damage and he had exhibited aphasia, but his speech had been fluent until onset of the cerebellar infarction. Results of analysis of speech samples included the following: (1) the patient showed very frequent syllable repetition and part-word repetition. (2) The stuttering occurrence rate at the second test was much higher than at the first test. (3) Almost all stuttering occurred on initial word sounds; stuttering on the medial and final word was less frequent. (4) Adaptation effect was absent. (5) Secondary behaviors such as closing of the eyes and grimacing were observed. The internal model related to cerebellar functions can be modified using feedback-error information. Results suggest that internal model dysfunction caused this patient's stuttering. EDUCATIONAL OBJECTIVES: After reading this text, the reader will be able to: (1) provide characteristics of neurogenic stuttering after the cerebellum infarction; (2) discuss the relationship between neurogenic stuttering and functions of the cerebellum.

Human brain response to visual stimulus between lower/upper visual fields and cerebral hemispheres.

We studied the human brain response to visual stimulation in which a square area was randomly presented in upper and lower visual fields (VFs). Seven normal volunteers carried out a contrast-based visual search task. Magnetic responses were detected in the bilateral parietal regions at 200-250 ms after stimulus onset. We compared the response latencies and strengths of the essential single sensor and root mean square (RMS) of the regions. The former evaluates the strength of neural activity with relatively high spatial resolution, while the latter evaluates the global neural activity. The single sensor and RMS latencies for the lower left VF were significantly longer than that for the upper left (paired t-test, P<0.05). The strengths did not differ between the upper and lower left VFs. There was no significant difference in latency or strength between the upper right and lower right VFs. These findings suggest that only left VF has different response properties in the upper versus lower VF, and that both local and global extrastriate activities are responsible for this anisotropy.