Parkinson's disease (PD) is a neurodegenerative disorder characterized by a progressive loss of midbrain dopaminergic (DA) neurons and a subsequent reduction in striatal dopamine. As a treatment for advanced Parkinson's disease, deep brain stimulation (DBS) of the thalamus was introduced in 1987 to treat tremor, and was applied in 1993 to the subthalamic nucleus. Now high-frequency stimulation of the subthalamic nucleus has become a surgical therapy of choice. Another surgical treatment is a cell replacement therapy. Transplantation of fetal dopaminergic (DA) neurons can produce symptomatic relief, however, the technical and ethical difficulties in obtaining sufficient and appropriate donor fetal brain tissue have limited the application of this therapy. Then, neural precursor cells and embryonic stem (ES) cells are expected to be candidates of potential donor cells for transplantation. We induced DA neurons from monkey ES cells, and analyzed the effect of transplantation of the DA neurons into MPTP-treated monkeys as a primate model of Parkinson's disease. Behavioral studies and functional imaging revealed that the transplanted cells functioned as DA neurons, attenuating the MPTP-induced neurological symptoms. DA neurons have also been generated from several human ES cell lines. Furthermore, functional recovery of rat PD models after transplantation was observed. One of the major problems in ES cell transplantation is tumor formation, which is caused by a small fraction of undifferentiated ES cells in the graft. So, it is essential for undifferentiated ES cells to be eliminated from the graft in order for transplantation to be feasible. These efforts will lead to clinical application of ES cell transplantation to the patients with PD.
Although nonconvulsive status epilepticus (NCSE) is a major neurological emergency, its frequency and clinical course are not well clarified. We investigated the clinical characteristics of status epilepticus focusing on the significance of NCSE. One thousand seven hundred twenty-three patients were admitted as neurological emergency cases in our hospital between October 2003 and September 2006. Of these cases, 94 (5.5%) were diagnosed as status epilepticus of which, 24 (25.5%) were diagnosed with NCSE on admission. Moreover, 8 patients who presented with convulsive status epilepticus on admission had episodes of NCSE during hospitalization. Thus, 32 patients (34.0%) suffered from NCSE during their clinical course. We analyzed the prognostic factors of status epilepticus using the Glasgow Outcome Scale. Poor outcome was significantly correlated with NCSE (p=0.003) and acute cerebrovascular disease (p=0.010), independent of age, sex, history of epilepsy, and other etiologies. Our study revealed that NCSE is not a rare condition and results in a poor outcome. Careful EEG evaluation of patients with consciousness disturbance might increase the diagnostic accuracy of NCSE, and aggressive treatment of patients with NCSE should be necessary to improve the prognosis of NCSE.
We herein report an autopsy case of a 63-year-old man with amyotrophic lateral sclerosis (ALS) who developed "ampulla cardiomyopathy." At the age of 56, he noticed a progressive weakness in his right upper extremity. One year later, a progressive weakness of the left upper extremity began. Dropped head and progressive weakness of the lower extremities emerged at the ages of 61 and 62, respectively. Intravenous immunoglobulin and plasma-exchange therapies did not improve his weakness. At the age of 63, one month before his death, he was hospitalized due to aspiration pneumonia. A tracheostomy was performed to secure his airway. Four days after the operation, an ST elevation of his electrocardiogram was incidentally found on the ECG monitor. An echocardiogram revealed diffuse hypokinesia of the wall of the left ventricle except in the basal portion, which is the typical finding of "ampulla cardiomyopathy." Wall motion of the left ventricle improved and his circulatory condition was stabilized after treatment, but his condition thereafter worsened again and he died 3 weeks later. An autopsy examination revealed diffuse fibrosis and degeneration of the cardiomyofibers. Neuropathological examination revealed neuronal cell loss, Bunina bodies and skein-like inclusions in the hippoglossal nuclei. In the thoracic spinal cord, degenarated anterior horn cells were seen and macrophage permeation in the corticospinal tract were shown by CD68 immunostaining. Therefore, the final neuropathological diagnosis was ALS. This report is the first autopsy case of ALS complicated with "ampulla cardiomyopathy."
A 57-year old woman had a five-day history of cough and high fever followed by abnormal behavior and headache with signs of meningeal irritation. A cerebrospinal fluid (CSF) exam revealed polymorphonuclear pleocytosis. Streptococcus pneumoniae was cultured from the patient's CSF and serum. Clinical features and laboratory investigations supported a diagnosis of pneumococcal meningoencephalitis. After treatment with intravenous meropenem (MEPM), the patient's laboratory data improved and her neck stiffness disappeared, but a brain MRI showed white matter lesions in the bilateral frontal and temporal lobes. The patient responded to pulse therapy with intravenous methylprednisolone (1g/day), carried out over three days: she recovered neurological function and her MRI lesions resolved. We report a case of acute meningoencephalitis caused by Streptococcus pneumoniae, mimicking acute disseminated encephalomyelitis (ADEM). We suggest that pneumococcal infection is one of the pathogenetic factors in ADEM.
Two cases (a 33-year-old woman and a 34-year-old man) were diagnosed as having cerebral tuberculosis. Case 1 was tuberculoma with miliary tuberculosis complicating cranial nerve palsies, and case 2 was tuberculous meningitis. Early diagnosis was difficult, because smear and PCR were negative. Culture was finally positive after several weeks. QuantiFERON were positive prior to the culture results in both cases. This reaction suggested tuberculous infection. QuantiFERON is useful for diagnosing cerebral tuberculosis at an early stage.
A 76-year-old woman developed weakness and sensory loss in the lower limbs and urinary disturbance in four days. She had a history of operation for the ascending colon cancer and lung metastasis one year ago. Neurological examination revealed flaccid paraplegia, absent Achilles tendon reflex, severe disturbance of superficial and deep sensation below the L3 level, and vesicorectal abnormality. Magnetic resonance imaging (MRI) studies showed an intramedullary T1-iso, T2-low lesion with Gd-DTPA contrast enhancement in conus medullaris at LI level. The laboratory examination revealed the elevated level of serum FDP, D-dimer and TAT. She was diagnosed as hematomyelia, which may be caused by the activation of coagulation and fibrinolysis system. We suggested that the ascending colon cancer and lung metastasis may contribute to the coagulation-fibrinolysis abnormality.
A 51-year-old woman started taking Chinese medicine containing ephedara herba as a nasal decongestant. One week later, she had three episodes of thunderclap headache, one during defecation and the others while taking a bath. She then had a convulsive seizure upon resolution of the second headache. A cranial CT did not show subarachnoid hemorrhage. Repeated CSF examinations showed neither xanthochromia nor inflammation. Brain diffusion-weighted and FLAIR MR images revealed high intensity lesions in bilateral hemispheres. A cerebral angiography showed multifocal segmental stenosis of bilateral cerebral arteries. Four months later, follow-up angiography showed normalized flow in all cerebral arteries and we gave a diagnosis of reversible vasoconstriction syndrome (RCVS). She has had no symptoms and signs since the third attack of headache. RCVS is an important disease in the differential diagnosis of thunderclap headache without neurological deficit. This is the first report of RCVS triggered by Chinese herbal medicine.
We report unique MRI abnormalities seen in a patient with Tolosa-Hunt syndrome (THS). A 60-year-old woman was admitted for left eye symptoms, including periorbital pain, numbness around the left eyebrow, blurred vision, delayed light reflex and impairment of abduction. Laboratory studies were unremarkable except for elevated erythrocyte sedimentation rates. T1-weighted MRI showed a mass lesion in the left orbital apex. Fat-suppressed T2-weighted MRI showed a hyperintense parallel linear lesion on the left optic nerve and a ring lesion around it, producing the "tram-track" sign on the axial view and the "donut configuration" on the coronal view. A diagnosis of THS was made, and corticosteroid therapy was started. Symptoms were improved rapidly, and MRI abnormalities disappeared. Reevaluation of MRI which had been taken at the previous episode of the right eye symptoms two years before also showed the "tram-track" sign and the "donut configuration" on the right. These signs are easy to be recognized and well reflect the stage of the disease. They are thus useful for diagnosing THS and evaluating the effect of the treatment. One should pay attention not only to the cavernous sinus and orbital apex, but also to the optic nerve for the MRI diagnosis of THS.
We report a 29-year-old man with subacute necrotizing lymphadenitis (SNL) associated with recurrent aseptic meningitis following an 11-year remission period. In both episodes, headache and fever were followed by lymphadenopathy, with increased serum IgE level. Although pleocytosis in cerebrospinal fluid was confirmed at admission in the first episode, it appeared at one week after admission in the second episode. Administration of glucocorticoid was effective for treating meningitis. The present case suggests a pathomechanism for SNL that involves both an immunological background and an acute viral infection as triggers of exacerbation of aseptic meningitis.
A 75-year-old right-handed woman was admitted to our hospital because of sudden onset of consciousness disturbance. She had taken angiotensin converting enzyme (ACE) inhibitor for hypertension. A neurological examination showed consciousness disturbance, total aphasia, right central facial palsy and right hemiparesis. Diffusion-weighted imaging revealed hyper-intense lesions in the middle cerebral artery territory, particularly in the insular cortex. Magnetic resonance angiography demonstrated occlusion of the left middle cerebral artery. Electrocardiogram monitoring during hospitalization detected an atrial fibrillation. Therefore, we diagnosed her as cardioembolic stroke. She was treated with intravenous alteplase of 0.6mg/kg. Sixty minutes after alteplase infusion, she developed orolingual angioedema. Immediately she was treated with methylprednisolone intravenously, and the angioedema improved. Orolingual angioedema should be considered as a complication associated with alteplase in a patient who has taking ACE inhibitor.