The number of patients with dementia is explosively increasing in major industrialized nations and Asian countries. It is estimated about 2,430,000 patients in the world, 4,000,000 patients in United States and more than 2,000,000 patients in Japan. The number of patients suffered from dementia is predicted to be 4,000,000 patients and occupy and 11% of Japanese population in 2040. Therapy for cure of dementia is still investigated. For this reason, dementia is the most important urgent and crucial concern in the national health and welfare. The major cause of dementia is Alzheimer disease. In this review, clinical symptom and natural course of Alzheimer disease, newly standardized criteria and neuropsychiatric butteries for Alzheimer disease are summarized. Possibility therapy to cure Alzheimer disease targeting Aβ oligomer and advances in research of biomarkers and amyloid imaging are also commented.
We conducted a nationwide survey of ALS patients on tracheostomy positive pressure ventilation (TPPV) who had developed a totally locked-in state (TLS) during the period from August to November 2006, in Japan. TLS occurred in 89 of 709 (13%) ALS patients on TPPV. On the second investigation, 29 of 41 patients with TLS showed complete palsy of more than two voluntary motor systems out of 4 motor systems [respiratory, pontine and medullar (bulbar), limb and external ocular motor systems] successively during a certain six months. The conventional classification of ALS based on the initial symptoms (bulbar, upper limb and lower limb type) was not found to be useful for predicting the onset of TLS. Seventy percent the patients developed TLS within 5 years after the start of TPPV. Thirty-seven (90%) patients finally developed total ophthalmoplegia at the onset of TLS, while one patient eventually developed complete bulbar palsy. One of 11 ALS patients with TLS, whom we experienced at Tokyo Metropolitan Neurological Hospital, also eventually showed complete palsy of the pontine (bulbar) motor system (inability to pull back the jaw). Due to the fact that TLS is a state of complete palsy of the voluntary motor systems for communication, which may occur during the course of ALS in around 15% of patients, further clinical investigation of TLS including cognition is thus considered to be essential for improving the palliative care of ALS patients on TPPV.
A 50-year-old woman presented with confusion, fever and drowsiness following an episode of headache and dizziness. On admission, neurological examination found positive pyramidal tract signs, meningeal irritation, and bilateral myoclonus in her arms. Laboratory tests revealed liver dysfunction, positive inflammatory reaction, elevated serum IgM antibody against cytomegalovirus, and increased cerebrospinal fluid protein of 67mg/dl. MRI of brain by diffusion weighted imaging showed a wide spread hyperintense lesion in white matter and limbic areas. We administered aciclovir, ganciclovir and steroid pulse therapy that showed a limited effect in the initial stage. In spite of all these therapies, she suffered from status epilepticus, followed by persistent disturbance of consciousness for about 2 months. However, her level of consciousness and motor deficit were gradually improved by continuous administration of ganciclovir. The present case indicates that prolonged disturbance of consciousness due to cytomegalovirus encephalitis could be restored with continuous ganciclovir administration.
We experienced 2 patients of valvular heart disease in Parkinson's patients taking cabergoline. Patient 1 was a 79-year-old woman who began taking 4 mg cabergoline daily after being diagnosed with Parkinson's disease (PD) in June 2003. She presented with dyspnea in November 2005. The patient had cardiomegaly, pulmonary congestion, and pleural effusion, and an echocardiogram showed valvular heart disease in the form of aortic regurgitation (AR) (grade I), tricuspid regurgitation (TR) (grade I), and mitral regurgitation (MR) (grade III). Cabergoline was thought to have caused these phenomena, so it was replaced with pramipexole, and after administration of diuretics and angiotensin-converting enzyme inhibitors (ACEIs) the patient's symptoms gradually disappeared. MR, AR and TR also disappeared 3 months later. Patient 2 was a 74-year-old woman who presented with sluggish movement in April 2001 and subsequently developed Parkinson's. While being administered 700 mg levodopa (Menesit) and 4mg cabergoline, the patient presented with shortness of breath in April 2005. An echocardiogram showed valvular heart disease in the form of MR (grade I) and TR (grade I). Heart function improved with the administration of diuretics. However, heart function again worsened in November 2005, and the patient presented with edema of the lungs and lower limbs. An echocardiogram in January 2006 showed worsening MR (grade III) and TR (grade II), and the patient also had pulmonary hypertension. ACEIs were administered along with diuretics and cabergoline was replaced with pramipexole, but the patient also developed malignant syndrome and disseminated intravascular coagulation (DIC) and later died. Patient 2 is the first case in Japan of death due to heart failure caused by the side effects of cabergoline. Caution is usually needed when treating a Parkinson's patient for valvular heart disease due to a dopamine agonist, and periodic checks for heart murmurs and echocardiography are crucial. When signs of heart failure develop during treatment with an ergot preparation of dopamine agonist, it is essential to immediately either stop the administration of the ergot preparation or change to a non-ergot preparation of dopamine agonist.
We report a 36-year-old man who admitted due to brain infarctions of the pons and cerebellum. He had a history of brain infarction 4 years ago. Chest radiograph and enhanced CT showed an abnormal shadow in the superior mediastinum. Chest enhanced CT showed dilated right and persistent left superior vena cava (PLSVC), and venous thrombus was detected in the thorax. The PLSVC connected directly to the left atrium. Abdominal CT showed surface irregularity of the bilateral kidney, suggesting that renal infarctions had occurred. There was no risk factor of systemic embolism except for PLSVC thrombosis. We thought that retention of blood flow caused the formation of thrombus in the PLSVC, and the thrombus flowed into directly the systemic circulation through the left atrium and caused multiple embolisms.
A 53-year-old man was admitted to our hospital after suffering four attacks with loss of consciousness and/or topographic agnosia. Three months after the first attack, the cerebrospinal fluid analysis showed no abnormal findings. IgG-autoantibodies and IgM-autoantibodies against glutamate receptor ε2 (GluRε2) were detected in cerebrospinal fluid and serum respectively. At that time, we diagnosed him as having limbic encephalopathy. Brain MRI revealed a high intensity lesion on T2-weighted and FLAIR images in the medial regions of the bilateral temporal lobes and splenium. A diffusion-weighted image revealed high intensity lesions which were also weakly enhanced by Gd-DTPA in the deep white matter beside the posterior horns. The patient then developed numbness in the right hand. The cerebralspinal fluid analysis, four months after the onset of the disease, exhibited slight pleocytosis and elevated protein. IgG-autoantibodies against GluRε2 were detected in the serum. The lesions beside the posterior horns were ring-like enhanced more strongly. Brain biopsy led to a diagnosis of glioblastoma. We suggest that patients with autoantibodies against GluRε2 should be carefully diagnosed with limbic encephalopathy associated with autoimmune mechanisms even if radiological findings are typical of the disease.
A 39-year-old man acutely developed diplopia, vertigo, unsteady gait, and disturbance of consciousness following an upper respiratory infection. Neurological examination showed ophthalmoplegia, facial paralysis, tetraplegia and loss of deep tendon reflexes. Babinski reflex was positive on the left and there were bilateral flexor withdrawal reflexes. He also developed ballism-like involuntary movements in all extremities, loss of proprioception predominantly on the left, and severe truncal ataxia. Anti-GQ1b IgG antibody was selectively elevated in serum, and CSF protein was elevated to 53mg/dl with cell count of 12/mm3. Nerve conduction study showed decreased amplitude of compound motor action potentials in all extremities, and no response in facial muscles. Cranial MRI showed no abnormalities whereas EEG was severely abnormal with lack of posterior dominant rhythm and the presence of continuous diffuse theta-waves. This case presented clinical characteristics of three syndromes concurrently-Fisher syndrome, Bickerstaff brainstem encephalitis, and Guillain-Barré syndrome-that may be collectively called 'anti-GQ1b IgG antibody syndrome'. The unique feature of the present case was development of deep coma and ballism-like movements, associated with selective increase of serum anti-GQ1b IgG antibody. It is thus conceivable that anti-GQ1b IgG antibody might underlie the pathogenesis of all three conditions.
A 69-year-old, right-handed, Japanese male patient presented with pure agraphia with topographical disorientation after hemorrhage in the right parietal lobe. Upon developing cerebral hemorrhage, he was referred to our hospital for close examination of agraphia. There was no paresis or clumsiness in his extremities. His speech was fluent and well-articulated. Neither aphasia nor reading impairments was found, although there was a clear writing impairment with effort and hesitation. His writing of both kanji and kana letters contained additional, absent or deformed strokes or parts. No hemianopia, prosopagnosia, constructional disturbances and dressing apraxia were found. He could recognize familiar buildings or landscapes, but often lost his way around well-known areas. MR images revealed subcortical lesions of precuneus, superior and inferior parietal lobules in the right hemisphere, around the posterior horn of the lateral ventricle. He revealed pure agraphia and topographical disorientation after the right brain haemorrhage, without dementia or personality change. These findings indicate that the right parietal lobe participates in the kinesthetic movements of writing. Some authers have been documented cases of aphasic agraphia or alexia with agraphia caused by right hemisphere damage in dextrals, but pure agraphia caused by the lesion in the right hemisphere is very rare.