An accumulating amount of evidence suggests that the white matter hyperintensities on T₂ weighted brain magnetic resonance imaging predict an increased risk of dementia and gait disturbance. This state has been proposed as cerebral small vessel disease, including leukoaraiosis, Binswanger's disease, lacunar stroke and cerebral microbleeds. However, the concept of cerebral small vessel disease is still obscure. To understand the cerebral small vessel disease, the precise structure and function of cerebral small vessels must be clarified. Cerebral small vessels include several different arteries which have different anatomical structures and functions. Important functions of the cerebral small vessels are blood-brain barrier and perivasucular drainage of interstitial fluid from the brain parenchyma. Cerebral capillaries and glial endfeet, take an important role for these functions. However, the previous pathological investigations on cerebral small vessels have focused on larger arteries than capillaries. Therefore little is known about the pathology of capillaries in small vessel disease. The recent discoveries of genes which cause the cerebral small vessel disease indicate that the cerebral small vessel diseases are caused by a distinct molecular mechanism. One of the pathological findings in hereditary cerebral small vessel disease is the loss of smooth muscle cells, which is an also well-recognized finding in sporadic cerebral small vessel disease. Since pericytes have similar character with the smooth muscle cells, the pericytes should be investigated in these disorders. In addition, the loss of smooth muscle cells may result in dysfunction of drainage of interstitial fluid from capillaries. The precise correlation between the loss of smooth muscle cells and white matter disease is still unknown. However, the function that is specific to cerebral small vessel may be associated with the pathogenesis of cerebral small vessel disease.

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Background: Lacunar transient ischemic attack (lacunar TIA) may have been underestimated because of diagnostic difficulties. The aim of our study was to classify TIAs by etiologic subtypes, especially using defined criteria for diagnosis of lacunar TIA and clarify clinical characteristics of lacunar TIA.
Method: 105 TIA patients out of consecutive 1,244 patients with acute ischemic stroke admitted to our hospital between January 2007 and June 2010 were enrolled in the present study. TIA was defined as an acute focal neurological deficit lasting less than 24 hours, suspected to be of cerebrovascular origin regardless of ischemic lesions on MRI. TIAs were classified to 5 etiologic subtypes; (1) cardioembolic TIA, (2) atherothrombotic TIA, (3) lacunar TIA, (4) other etiologies, and (5) undetermined etiology and clinical characteristics in each subtype and the incidence of recurrent stroke after TIA were investigated. Lacunar TIA was diagnosed if the following criteria were fulfilled; (1) presence of lacunar infarct on MRI and/or the presence of unilateral dysfunction of at least two of three body parts (face, arm, leg) in the absence of cortical dysfunction presumed due to subcortical ischemia. (2) absence of cardiac sources of embolism and large artery atherosclerosis.
Results: In 105 patients with TIA, lacunar TIA was the most frequent etiology (31%) followed by cardioembolic TIA (27%), atherothrombotic TIA (19%), undetermined etiology (18%), and other etiologies (6%). In patients with lacunar TIA, history of repeated TIA was more frequent and systolic blood pressure on admission was higher significantly than in cardioembolic TIA. Six of 105 patients had experienced recurrent stroke after TIA during admission. Among these 6 patients, 3 patients were diagnosed as lacunar infarctions.
Conclusions: Lacunar TIA was most common TIA subtype in the present study. It is critical to identify lacunar TIA on admission because some patients with lacunar TIAs experience early recurrent stroke.

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We report a 61-year-old man with slowly progressive gait disturbance and paresthesia in the lower extremities following a total gastrectomy for gastric cancer 23 years previously. The patient presented with hyperreflexia, peripheral sensory neuropathy, and cerebellar ataxia. Magnetic resonance imaging showed atrophy of the cerebellum, and electrophysiological findings suggested the presence of disorder in both sides of the pyramidal tract, dorsal column, peripheral nerves, and optic nerve. Laboratory findings revealed anemia, neutropenia, and a remarkably low serum copper level (10μg/dl; normal: 68-128). His serum vitamin E was slightly low and his serum vitamin B₁₂ was within the normal limits. After administering an oral copper supplement, his symptoms improved with normalization of the serum copper level.
We need to pay attention to myeloneuropathy caused by copper deficiency if the patient has a past history of total gastrectomy.

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A 57-year-old man developed bilateral hands and feet numbness, followed by weakness with the legs and skin pigmentation. These symptoms became gradually worsened, and we made a diagnosis of POEMS syndrome because of progressive polyneuropathy, skin changes, IgG lambda type monoclonal proteinemia, and elevated level of serum vascular endothelial growth factor (VEGF). Diffusely enlarged pancreas was noticed in computed tomography. Serological, radiological, and histological findings revealed enlarged pancreas was due to IgG4-related autoimmune pathogenesis. After high dose chemotherapy with autologous peripheral stem cell transplantation, his clinical manifestations, IgG lambda type monoclonal proteinemia, and elevated level of serum VEGF were improved, whereas diffuse enlargement of the pancreas did not change. This is the first case report of POEMS syndrome accompanied with IgG4-related autoimmune pancreatitis. Co-existence of monoclonal and polyclonal plasmaproliferative changes in the present patient may provide keys to clarify common mechanisms shared by these two rare disorders, POEMS syndrome and IgG4-related autoimmune disease.

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A healthy 40-year-old man was admitted to our hospital because of impaired consciousness and convulsions starting five days after a high fever. Though rapid influenza diagnostic tests were negative, RT-PCR assay detected influenza A (H1N1) 2009 viral RNA from nasopharyngeal swab specimens. Initially high concentrations of interleukin-6 (IL-6) in serum and cerebrospinal fluid decreased as the symptoms improved, as with past influenza-associated encephalopathy cases. Scattered high signal intensity lesions in the cerebral cortex and right medial thalamus on magnetic resonance imaging (MRI) disappeared, and diffuse brain atrophy remained. It is necessary to be aware of the possibility of healthy adults developing pandemic 2009 influenza A (H1N1)-associated encephalopathy and that rapid influenza diagnostic tests have limited accuracy.

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A Japanese male with no family history of neurological disease or dementia showed behavioral abnormalities including egocentric and antisocial behavior at the age of 80. Over the next few years, other psychiatric symptoms such as allotriophagy and stereotypical behavior were also observed and his abnormal behavior became a social problem. Neurological examination revealed no apparent motor abnormalities, pyramidal and extrapyramidal signs, or ataxia. Aphasia, including semantic dementia was not apparent. The severity of memory disturbance was relatively milder than his psychiatric symptoms. Daily living activities and conversational ability were relatively maintained until shortly before his death at the age of 86. The clinical diagnosis was Alzheimer disease.
Autopsy revealed that the brain weighed 950g; frontotemporal atrophy with lateral ventricular dilatation was apparent. Neuron loss, gliosis, and tissue rarefaction were recognized in the frontotemporal cortex, subiculum, transentorhinal cortex, amygdala, and insular cortex and were particularly noticeable in the superficial layer of the cortex. Many ubiquitin-positive/TDP-43 positive but tau-negative dystrophic neurites with a few neuronal cytoplasmic inclusions were widely observed. Neuronal cytoplasmic inclusions were also observed in the dentate gyrus of the hippocampus. Although the spinal cord was not investigated, there was no apparent involvement of the motor neuron system. Small numbers of neurofibrillary tangles and senile plaques were observed, corresponding to Braak stage II and CERAD stage B, respectively. Argyrophilic grains, Lewy bodies and Pick bodies were not observed. The patient was pathologically diagnosed with frontotemporal lobar degeneration with ubiquitin-positive/TDP-43-positive inclusions (FTLD-TDP) and without motor neuron disease. No mutation was found in the TDP-43 gene.
We considered the psychiatric symptoms and head CT findings of the present patient to be important observations for helping to discriminate between Alzheimer disease or other neurodegenerative diseases with dementia, and FTLD-TDP.

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Zamboni et al proposed a new hypothesis for the pathomechanisms of multiple sclerosis (MS): chronic cerebrospinal venous insufficiency (CCSVI). Using Doppler ultrasound and venograms, they found severe extracranial venous stenosis in MS patients. They suggested that a venous obstruction in the neck caused a reflux back into the brain, which led to edema and demyelination.
We examined the blood flow and the cross-sectional area of the internal jugular veins using Doppler ultrasound (Vivid 7 PRO, GE Health Japan, Tokyo) in 17 MS (8 males and 9 females; 20-58 years of age, median 38 years) and 11 neuromyelitis optica (NMO) Japanese patients (1 male and 10 females; 23-60 years of age, median 44 years). Nine of the 11 NMO patients were seropositive for anti-aquaporin4 antibodies.
We did not find any obstruction or stenosis of the internal jugular veins in any patient. Other disorders such as bilateral internal and external jugular venous ligation or radical neck dissection, which result in venous stasis, are not known causes of demyelination in the central nervous system. Our data also does not support the hypothesis of CCSVI theory, despite the fact that our study was limited to a small group of patients and the examination was performed only using Doppler ultrasound.

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