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Brain white matter lesions (WMLs), which are often observed in patients with ischemic cerebrovascular diseases, contribute to cognitive decline. We analyzed the pathologic and regenerative processes in brain white matter lesions of patients diagnosed with vascular dementia. There was a significant increase in the number of oligodendrocyte progenitor cells (OPCs) in the brains of patients with vascular dementia as well as in rats with cerebral hypoperfusion. WMLs can be induced experimentally by bilateral common carotid artery ligation (BCCAL) of rats to cause chronic cerebral ischemia. After chronic cerebral hypoperfusion injury, oxygen free radicals and activated microglia acting as inflammatory elements contribute to chronic cerebral hypoperfusion-induced WMLs. The cell death of oligodendrocytes (OLGs) contributes directly to WMLs. The activation for intracellular signaling pathway of cAMP responsive element binding protein (CREB) phosphorylation in the white matter was suppressed after BCCAL. Type III phosphodiesterase inhibitor (PDE3-I) has potential therapeutic and brain-protective effects based on multitarget mechanism through cell signaling pathway of CREB phosphorylation. The OPCs subsequently underwent cell death and the number of OLGs decreased. In the rat model, PDE3-I prevented cell death, markedly increased the mature OLGs, and promoted restoration of white matter and recovery of cognitive decline.

In the past, transient ischemic attack (TIA) was defined as any sudden, focal cerebral ischemic event with neurological deficit lasting <24 hours. However, in several series of patients with TIA who underwent diffusion-weighted magnetic resonance imaging, many ischemic episodes with symptoms lasting <24 hours are associated with new infarctions. Therefore, TIA working group proposed a new tissue-based, rather than a time-based, definition of TIA: "a brief episode of neurological dysfunction caused by a focal disturbance of brain or retinal ischemia, with clinical symptoms typically lasting less than 1 hour, and without evidence of infarction". The latest definition of TIA is "a transient episode of neurological dysfunction caused by focal brain, spinal cord, or retinal ischemia, without acute infarction". Recent studies have shown that stroke risk after TIA is high in the first few days. Two prognostic scores for short-term risk of stroke after TIA have been proposed: the California score and the ABCD score. The ABCD(2) score has the same components as ABCD, but with diabetes mellitus added. This score was a more accurate predictor than either of the previous scores. Antiplatelet therapy should be prescribed immediately for the secondary prevention of stroke in patients with a noncardioembolic TIA.

Adult-onset type II citrullinemia (CTLN2) is a hereditary metabolic disorder characterized by highly elevated plasma citrulline and ammonia. Recent studies have identified the "citrin gene" (SLC25A13) as the causative gene for CTLN2. Various neurobehavioral symptoms seen in this disease, such as unconsciousness, disorientation, abnormal behavior, and epilepsy, are thought to be caused by encephalopathy mostly due to hyperammonemia. A 47-year-old woman presented with repeated unconsciousness and abnormal behavior. The high plasma anmonia level was not always associated with her neurobehavioral symptoms (unconsciousness, disorientation, abnormal behavior, and epilepsy), but paroxysmal EEG discharges were invariably associated with these symptoms. Her symptoms and abnormal EEG discharges were sometimes treated with diazepam simultaneously. Based on these findings, we considered that her symptoms were caused by nonconvulsive status epilepticus (NCSE). Until date, neurobehavioral symptoms of CTLN2 are considered to be caused by hyperammonemia or other metabolic factors. We suggest that encephalopathy of CTLN2 is caused not only by hyperammonemia but also by NCSE. Therefore, repeated EEG monitoring is recommended in the follow up of patients with CTLN2.

We report a 60-year-old man with chronic inflammatory demyelinating polyneuropathy (CIDP) accompanying systemic lupus erythematosus (SLE) and Sjögren syndrome (SS). He was admitted to our hospital because of progressive weakness and dysesthesia in the distal parts of the bilateral upper and lower extremities. We diagnosed the illness as CIDP and treated him with steroids, plasma filtration and high-dose intravenous immunoglobulin therapy (IvIg). Consequently, his symptoms improved gradually and he was discharged. However, 2 years after the first admission, he experienced dyspnea on effort and chest X-ray demonstrated right pleural effusion. Consequently, he gradually developed gait disturbance, loss of taste, and severe dysesthesia in his lower limbs. Therefore, he was admitted again. On neurological examination, mild weakness was detected in all limbs distally. Deep tendon reflexes were absent. The sensation of position and vibration was diminished in the fingers and toes. He could not walk by himself and demonstrated an ataxic gait with a wide base. Examination of cranial nerves demonstrated no abnormalities, except for loss of taste. Serological examination demonstrated positive auto-antibodies including antinuclear, anti-DNA, and anti-SS-A antibodies. Urinalyses showed albuminuria and microscopic hematuria. Cerebrospinal fluid (CSF) was clear and colorless, containing 3 mononuclear cells per cubic mm, with a protein of 275 mg/dl. Magnetic resonance images (MRIs) of the brain and entire spine were normal. Neurophysiological studies demonstrated an absence of sensory nerve action potentials in the right arm and markedly slow conduction velocities, conduction block in the ulnar forearm segment and absence of F waves in all limbs. The renal biopsy revealed lupus nephritis. The lip biopsy demonstrated chronic sialoadenitis consistent with SS, altough patient did not show symptoms of arthritis or vasculitis. It is well known that mononeuritis multiplex and acute demyelinating polyneuropathy accompany SLE. However there are few reports that describe the occurrence of CIDP in patients with SLE, and the association of "CIDP-like" neuropathy in patients with SS. Our case suggests that the autoimmune disease associated with SLE and SS may induce "CIDP-like" inflammatory demyelinating polyneuropathy.

We report an 81-year-old patient with progressive dementia, disinhibition, and gait disturbance. He showed visuospacial disorientation, apathy, and gait disturbance at 76 years of age. When he was 77 years old, he was diagnosed Parkinson's disease and treated with the 1-dopa, the dopamine agonist, the amantadin, and the anti-cholinergic drug. These treatments didn't improve his motor disturbances. His motor disturbances, apathy, and abnormal behavior progressed gradually. He was admitted to the hospital at the age of 77. He was severely demented and akinetic. Sometime, violent behavior and hallucination were seen. The brain MRI showed frontotemporal lobe atrophy and severe leukoaraiosis of the frontal white matter. At 79 years of age, he became mute and bedridden. When he was 80 years old, large infarction occurred in his occipital lobe. He died due to renal failure and respiratory suppression at 81 years of age. His brain was examined pathologically. At the neurological CPC, the chief discussant arrived at the conclusion that his diagnosis was Binswanger's disease. Other possibilities discussed were FTD, CBD, and progressive subcortical gliosis. The post-mortem examination revealed diffuse white matter degeneration due to atherosclerotic change of the small artery, many lacunar infarctions, and severe infarction of the occipital lobe. These findings led the diagnosis of Binswanger's disease and cerebral infarction.

We report a patient who developed personality change, dementia and parkinsonism. The patient was a Japanese woman who died at age 76. She developed memory problems at age 63. At age 66, she started showing personality changes, and began having short-step gait and mask-like face. On admission to our hospital at age 68, neurological examination showed mild memory deficit and postural instability. Six months after discharge, she developed delusion, rigidity, tremor, and gait disturbance. Her condition relentlessly progressed and she became bedridden at age 71. CT scan revealed marked atrophy of the frontotemporal lobes with enlargement of the lateral and third ventricles. The patient died at the age of 76 years. The patient was discussed in a neurological CPC, and a chief discussant arrived at the conclusion that the patient had frontotemporal dementia. Some participants thought that she had Pick disease or diffuse Lewy body disease. Severe atrophy of the frontal lobe and anterior part of the brain was seen at autopsy. Neuropathological examination showed severe neuronal loss with gliosis in the substantia nigra, pallidum, thalamus, and hippocampus. Moderate loss of neurons with gliosis was seen in the frontal and anterior temporal cortex. Argyrophilic and tau-positive neuronal inclusions which showed various shapes including Pick body-like inclusions and globose type of neurofibrillary tangles, were seen in the cerebral cortex and caudate. Argyrophilic and tau-positive astrocytes were also observed in the cerebral cortex. The pathological diagnosis was an unusual form of frontotemporal lobar degeneration with various tau-positive inclusions.

We report a 67-year-old man with rt. hand resting tremor and rigidity after lt. putaminal hemorrhage. He had hypertension and alcoholic liver cirrhosis as past history. When he was 62 years old, he realized rt. hemiplegia suddenly and admitted in Juntendo Urayasu hospital. Brain CT showed intracranial hemorrhage in lt. putamen. He was treated with neurosurgery operation for rejecting hemorrhage. Mild rt. hemiparesis remained but he could live independently. He was medicated sulpiride for depression after cerebrovascular accident. On 63 years old, resting tremor and rigidity appeared on his rt. hand. His doctor stopped sulpiride and treated with L-Dopa/Benserazide and trihexiphenidyl. His parkinsonism was stable with this treatment for four years. His doctor considered that he was Parkinson's disease or drug-induced parkinsonism. On 67 years old, he became akinetic-mutism state suddenly and admitted in the hospital. His consciousness turned alert soon and discharged after two weeks. This episode was considered as epilepsy. After one week from discharge, he was found cardio-pulmonary arrest and confirmed dead in the hospital. Post-mortem examination revealed necrosis in the posterior-lateral part of lt. putamen due to hemorrhage. However, there was no degenerative change of the striatum or the substantia nigra and no Lewy bodies in his brain. Other pathological changes were also not found. His parkinsonism might be caused putaminal pathology due to hemorrhage.

Recent advances in neuro-imaging technology assist early clinical diagnosis for ischemic stroke subtype. The precise early diagnosis for stroke subtype plays an important role for the management in patients with acute cerebral infarction. The differential diagnosis is made according to the algorithm in the modified the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification, with reference to the results of diffusion-weighted MRI and MRA. Artery-to-artery embolism and branch atheromatus disease are diagnosed as atherothrombotic infarction according to this algorithm. Thrombolytic therapy is recommended in cardioembolic stroke within 3 hours after onset. The anticoagulant therapy with heparin is often used to prevent the recurrence for thrombosis in acute cardioemboic infarction. The selective thrombin inhibitor has recently been used in the treatment of acute atherothrombotic infarction. The antiplatelet therapy with aspirin is recommended in acute atherothrombotic infarction and lacunar infarction. The sodium ozagrel is recommended in the treatment of acute lacunar infarction. The treatment of acute ischemic stroke should be managed according to Japanese Guidelines for the management of stroke (2004).

We report a 66-year-old woman with Hashimoto's encephalopathy who showed rapidly developing cognitive deficits, inactivity, and gait disturbance without involuntary movements or convulsions. She had had right-sided hemiparesis and dysarthria caused by a lacunar infarction and had been admitted to our hospital for 2 weeks. Although the dysarthria and hemiparesis gradually improved, difficulty in walking, disorientation, and drowsiness developed 2 months after discharge. Upon readmission, the patient was alert but apathetic and sometimes sleepy. The right upper and lower limbs showed mild weakness, which was considered to be due to the previous infarction. Cerebrospinal fluid showed mild elevation of protein without pleocytosis. An electroencephalogram was normal, and a magnetic resonance imaging of the brain showed only the old lacunar infarction. Titers of antithyroglobulin antibodies and levels of thyroid stimulating hormone in serum were elevated. We made a diagnosis of Hashimoto's encephalopathy and treated the patient with high-dose corticosteroids. Within 1 week, her mental status improved and she was able to walk. Generalized seizure, myoclonus, and tremor, which are characteristic of Hashimoto's encephalopathy, never developed. The findings in this patient suggest that Hashimoto's encephalopathy, a treatable condition, should be included in the differential diagnosis of dementia.

We report a 52-year-old Japanese woman who developed dyskinesia, epilepsy, and gait disturbance. She was well until 35 years of age, when she noted the onset of gait disturbance. She also noted abnormal involuntary movements in her limbs. She also noted dysarthria at age 38. A neurologist examined her at age 41. The neurologist found cerebellar ataxia and dyskinesia. The atrophy of the brain stem and the cerebellum was on CT. She started to have generalized convulsion with loss of consciousness. Dementia became apparent at age 40. In October, 1993, she became psychotic in which she behaved violently taking off her clothes shouting as "Fire". She was treated with major tranquilizers and became quiet. However, choreic movements became prominent. Her subsequent course was complicated with dysphagia, dementia, convulsion, and frequent bouts of pneumonia. She expired on January 24, 2000 after developing pneumonia. Her father and one sibling had similar motor disturbances. She was discussed in a neurological CPC. The chief discussant arrived at conclusion that the patient had dentatorubral-pallidoluysian atrophy. Most of the participants agreed with this diagnosis. Postmortem examination revealed that entire brain looked smaller than normal including the brain stem and the cerebellum. The cerebellar dentate nucleus showed loss of neurons and gliosis; glumose degenerations were also seen. The external segment of the pallidum showed neuronal loss and gliosis. The subthalamic nucleus showed gliosis without neuronal loss. A demyelinated focus was found in the pons; the lesion looked similar to central pontine myelinolysis. The cerebral white matters were unremarkable. Other areas were unremarkable. The pathological diagnosis was dentatorubral-pallidoluysian atrophy. The pathologic lesion which might explain her dementia was not apparent.

Medullasin levels in granulocytes of patients with neurological diseases and healthy volunteers were determined by the enzyme immunoassay using mouse monoclonal antibodies against human medullasin and o-phenylenediamine-H2O2 as the detection system of the enzyme activity. One hundred twenty-one out of 159 patients with multiple sclerosis (76.1%) showed positive results (above means of normals + 2SD) in this test, while only 16.9% (24/142) of patients with non-inflammatory neurological diseases had positive results. This enzyme immunoassay method for medullasin is considered to be an useful paraclinical test for the diagnosis of multiple sclerosis.