Miliary brain metastasis presenting with dementia: progression pattern of cancer metastases in the cerebral cortex.

We report an autopsy case of an 82-year-old woman with progressive dementia due to miliary brain metastasis from lung adenocarcinoma. The patient presented with dementia 5 months prior to death and suddenly died of pulmonary hemorrhage. Postmortem examination revealed normal appearance of the brain. However, there were numerous foci of cancer metastasis in all parts of the brain on light microscopic examination. The carcinoma cells were located in the perivascular (Virchow-Robin) space and did not invade to the brain parenchyma. The carcinoma cells were also found in the subpial space. In the cerebral cortex, foci of metastasis appeared to spread in the following way: tiny foci of metastasis initially occur in the middle cortical layer, then spread to all layers through the perivascular space, and finally reach the subpial space and subcortical white matter. Although the junction between gray and white matter is a preferred site for usual brain metastasis, middle cortical layer was considered to be the initial site for metastasis in our patient. The perivascular pial sheath plays an important role for the development of miliary brain metastasis.

Disseminated intraparenchymal microgranulomas in the brainstem in central nervous system sarcoidosis.

We report a 70-year-old woman with sarcoidosis and multiple cranial nerve palsy. The patient suffered from dysarthria, dysphagia and weakness of the upper and lower extremities and died of sepsis. No abnormalities were noted in brain MRI. At autopsy, numerous epithelioid granulomas with Langhans giant cells were present in the bilateral lungs, including the hilar lymph nodes. The brain had a normal external appearance. Histologically, there were brainstem parenchymal lesions consisting of many microgranulomas, lymphocytic infiltration, activated microglias and astrocytosis. Perivascular lympocytic cuffing was also seen. Neither granulomas nor lymphocytic infiltration were seen in the leptomeninges. The present case was considered to be a peculiar type of neurosarcoidosis, that is, "sarcoid brainstem encephalitis".

[A case of young adult presenting with cerebral infarction caused by homocystinuria].

Homocystinuria is a congenital metabolic disorder, and has been known as life-threatening risk factor of vascular disease including ischemic stroke. We report a case of cerebral infarction due to homocystinuria. The patient was a 21-year-old woman exhibiting left hemiparesis and a previous history of ectopia lentis. Magnetic resonance imaging showed multiple fresh infarctions in the right frontal and temporal lobes, basal ganglia, corona radiata, and internal capsule. The right common carotid angiogram demonstrated complete occlusion at the origin of the right internal carotid artery. Further investigation clarified increased level of serum methionine and homocysteine and urinary homocystin due to cystathionine beta-synthase deficiency. Homocystinuria was diagnosed as the cause of cerebral infarction. The patient was treated by low methionine diet and administration of folic acid, cobalamin, and aspirin. It should be recognized that some patients with homocystinuria are missed in the neonatal screening for congenital metabolic disorders. Recent studies indicated that the homocysteinemia is one of risk factors of ischemic stroke in the general population as well as in the patients of homocystinuria. We recommend metabolic screening for homocystinuria, when treating a juvenile patient with ischemic stroke of unknown etiology.

Multinucleated astrocytes in old demyelinated plaques in a patient with multiple sclerosis.

A 51-year-old woman with MS of 26 years duration is reported. The patient's MS history began at the age of 25 years with an initial relapsing-remitting course, followed by slow progression without distinct relapses. She became bed-ridden at the age of 40 years. A post-mortem examination revealed numerous demyelinated plaques that exhibited fibrillary gliosis with Rosenthal fibers, but without lymphocytic cuffing or foamy macrophages. Activated microglia were found mainly in the marginal portion of the plaques. These plaques were consistent with so-called 'slowly expanding plaques'. Interestingly, multinucleated astrocytes were observed within the plaques, being more numerous in the area where microglial infiltration had occurred. These findings suggest that mild persistent inflammatory processes are present even in old plaques and that certain inflammatory stimuli cause multinucleation of astrocytes. This might explain the gradual deterioration without definite relapses observed in the late stage of MS.

[Epstein-Barr virus-associated encephalitis presenting as refractory status epilepticus that persisted for nearly 2 months with excellent recovery].

A 37-year-old woman presented with Epstein-Barr virus (EBV)-associated encephalitis that developed into refractory status epilepticus ten days after the onset of headache and fever, without signs suggestive of infectious mononucleosis. An electroencephalogram showed definite epileptogenic changes, including diffuse slow wave bursts with paroxysmal generalized bilateral sharp waves. The patient required general anesthesia for nearly two months, but had completely improved 18 months later. The patient developed Klüver-Bucy syndrome four months after the onset: bilateral frontal hypoperfusion was detected with SPECT at this time, but also improved after 18 months. MRI showed a 2-3 mm lesion of the cerebellar white matter, which was suggestive of a small demyelinaed focus. The patient's serum was positive for EBV DNA within two weeks of onset, but negative there-after. However, the CSF was positive for EBV DNA for more than five months, with a four-fold increase in the titers of IgG antibody for EBV-viral capside antigen in the CSF. Given the patient's good recovery from her critical condition, her severe encephalitis/encephalopathy with persistent status epilepticus probably resulted from an EBV-associated immune-response after the reactivation of EBV, rather than from a direct infiltration of EBV into the brain.

Posterior encephalopathy subsequent to cyclosporin A presenting as irreversible abulia.

A case of cyclosporin A (Cys A)-induced posterior encephalopathy developed into persistent abulia despite rapid and marked improvement of abnormal T2- and FLAIR MRI hyperintense regions. Diffusion-weighted MRI signal intensity was also high at the onset. This change is atypical in Cys A-induced encephalopathy and was thought to predict poor recovery from the encephalopathy. Persistent abulia was probably due to marked hypoperfusion in the whole cortex including bilateral frontal lobes and basal ganglia as detected by SPECT. Apart from the breakdown of the blood-brain barrier, direct toxicity of Cys A to the brain may play a role in the pathogenesis of chronic, irreversible encephalopathy.

[A case of Fisher's syndrome after Haemophilus influenzae infection].

We report a case of Fisher's syndrome with serological evidence of antecedent Haemophilus influenzae infection. A 66-year-old woman developed unsteady gait and multiple cranial nerve palsies after upper respiratory infection. Serum anti-GQ 1 b and anti-GT 1 a IgG antibodies were positive. In the acute phase of the illness, her serum had high titers of IgM, IgG and IgA anti-H. influenzae antibodies, which significantly decreased during the clinical course. Further study is needed to clarify the clinical and immunological features of Fisher's syndrome after H. influenzae infection.

[Tandospirone citrate, a selective 5-HT1A agonist, alleviates L-DOPA-induced dyskinesia in patients with Parkinson's disease].

A rapid and excessive increase in extracellular dopamine(DA) after L-DOPA administration is considered one of the major causes for L-DOPA-induced peak-dose dyskinesia. Therefore, inhibition of excessive rise in L-DOPA-derived DA is likely to be an ideal treatment for L-DOPA-induced dyskinesia. Based on our previous experimental studies that 8-OH-DPAT, a potent 5-HT1A agonist, attenuates an increase in L-DOPA-induced extracellular DA in the striatum of the rat model of Parkinson's disease, we hypothesized that L-DOPA-induced dyskinesia in patients with Parkinson's disease is alleviated by a 5-HT1A agonist. In the present study, we administered tandospirone citrate, a selective 5-HT1A agonist, to patients with Parkinson's disease suffering from L-DOPA-induced dyskinesia. Tandospirone(15-60 mg/day) was administered to 10 patients with L-DOPA-induced peak-dose dyskinesia. Twelve weeks after tandospirone treatment, duration of dyskinesia, subjective and objective severity of dyskinesia, and parkinsonian features were evaluated. Severity of dyskinesia was decreased in 5 patients; among these, 3 patients experienced slight worsening of parkinsonian features. Four patients showed no change in dyskinesia; among these, 2 patients showed worsening of parkinsonian features. One patient had slight worsening of dyskinesia without any change in parkinsonian features. The present study demonstrated that tandospirone is effective in alleviating L-DOPA-induced dyskinesia in 50% of the patients. However, at the same time 50% patients showed slight worsening of parkinsonian features. Both the anti-dyskinetic effect and the worsening of parkinsonian features are thought to be induced by tandospirone's potent 5-HT1A agonistic activity. Diverse effect of tandospirone may be caused by its partial agonist activity on 5-HT1A receptors, or may indicate that other causes for the expression of dyskinesia exist apart from excessive rise in brain DA levels. Administration of a 5-HT1A agonist is a choice for patients with dyskinesia if the care is taken so as not to induce worsening of parkinsonian features. Further studies such as double-blind trials are needed to confirm the usefulness of a 5-HT1A agonist for L-DOPA-induced dyskinesia.