A 77-year-old man with gait and gaze disturbance]

We report a 77-year-old Japanese man with progressive gait disturbance. He was well until his 71 years of the age (1992), when he noted an onset of disturbance in his speech, which was followed by difficulty in using his left hand. He did not attempt to use his left hand afterwards. He started to fall down in the spring of 1994. He was admitted to our service on October 6, 1994. Neurologic examination revealed an alert and oriented man. He showed limb-kinetic apraxia in his left hand with anosognosia for his apraxia. Vertical gaze was impaired. He walked in small steps. He had moderate axial and limb rigidity. He had no weakness, ataxia, or tremor. Deep tendon reflexes were normal. Plantar response was flexor. Sensation was intact. His gait had progressively become worse and he was admitted to another hospital in April of 1996. At that time he was disoriented to time. He was only able to walk a few steps with support. He continued to show limb-kinetic apraxia in his left hand. He developed dementia and dysphagia and he expired on October 27, 1998. He was discussed in a neurological CPC, and the chief discussant arrived at the conclusion that the patient had corticobasal degeneration. Most of the participants agreed with this diagnosis, but a few of them thought that progressive supranuclear palsy would be more likely. Post-mortem examination revealed no gross cortical atrophy. The right hemisphere was kept frozen for future biochemical analysis. The left precentral gyrus showed spongy changes, neuronal loss and gliosis. The pallidum, putamen, and the subthalamic nucleus were unremarkable, however, neurofibrillary tangles were seen in the subthalamic nucleus. The substantia nigra showed only slight neuronal loss; neuronal pigments were well retained. A few neurofibrillary tangles were seen in the remaining neurons. The cerebellar dentate nucleus showed grumose degeneration. Gallyas-Braak staining revealed many tuft-shaped astrocytes in the precentral gyrus. Pathologic diagnosis was progressive supranuclear palsy. Some participants thought that this diagnosis was unacceptable, because the pathologic changes in the substantia nigra, globus pallidus, and the subthalamic nucleus, which were usually severely involved in PSP, did not show typical changes of PSP. In addition, the predominant clinical feature was limb-kinetic apraxia, although he showed vertical gaze paresis and parkinsonian gait, which could also be seen in corticobasal degeneration. There was a big discussion among participants with regard to the diagnosis.     

A 67-year-old man with progressive disturbance of gait]

We report a 67-year-old man with progressive disturbance of gait. He was well until the spring of 1993 (62 years of the age), when he noted an onset of unsteady gait. He also noted that he started to have a difficulty in playing tennis, in which he became unable to hit the ball with his racket. He also noted parkinsonian features such as bradykinesia and loss of hand dexterity. He was treated with levodopa, which did not improve his symptoms. His MRI revealed marked atrophy of the cerebellum and the pons. The criss-cross high signal lesion was seen in the center of the pons. The third ventricle was dilated. The putamen was unremarkable. His subsequent course was complicated by easy to fall, difficulty in swallowing with episodes of aspiration pneumonia. He also developed nocturnal apneustic episodes. He was admitted to our hospital on November 15, 1998, when he was 67 years of the age. He had low grade fever and low blood pressure (98/70). He was anemic but not icteric. Tumors were palpated in his jaw, anterior chest, and in the left arm. He was alert but unable to convey his desire because of dyspnea and tracheostomy. His gaze was slightly restricted in the horizontal direction and markedly so in the vertical direction. Motor functions were difficult to evaluate. His clinical course was complicated by atelectasis of the right lung and pleural effusion. He developed marked edema and oliguria. He developed sudden bradycardia and expired on December 26, 1998. He was discussed in a neurological CPC and the chief discussant arrived at the conclusion that the patient had multiple system atrophy. Majority of the audience agreed with this diagnosis. Post-mortem examination revealed a lung cancer in the right lung (undifferentiated adenocarcinoma) with metastases to the liver, kidneys, lymph nodes, pericardium, pleura, skin, bone marrow, and the brain. Neuropathologic examination revealed marked atrophy of the pons and the cerebellum. The putamen showed brownish discoloration and atrophic changes. The substantia nigra showed marked neuronal loss and gliosis. Oligodendrocytic inclusion bodies (alpha-synuclein positive) were seen in the putamen, globus pallidus, substantia nigra, pontine nucleus, cerebellar white matter, internal capsule, cerebral peduncle, and the spinal cord. These findings are consistent with the pathologic diagnosis of multiple system atrophy. What was interesting to us was the presence of neurofibrillary tangles in the substantia nigra, nucleus ruber, globus pallidus, and subthalamic nucleus. Tuft-shaped astrocytes were also seen. This patient appears to be a rare example of combination of MSA and PSP.     

A 76-year-old woman with personality change, dementia and parkinsonism]

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.     

A 52-year-old woman with dyskinesia, epilepsy and gait disturbance]

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.     

行走不稳 四肢麻木疼痛

病历摘要患者男性,52岁。主因行走不稳约15 d,2012年8月30日入院。患者入院前约15 d无明显诱因出现行走不稳、易跌倒,但尚可感觉地面平实,曾出现穿鞋上床,伴双侧掌心刺痛及小腿中下段麻木感,无头痛、头晕、复视、饮水呛咳、吞咽困难等症状。病情呈进行性加重,逐渐进展为不能独立行走、站立,吃饭时不能准确地将勺子送入口中,言语含糊,反应稍迟钝,短时记忆减退。自发病以来精神、食欲欠佳,大小便如常,近2年来体质量下降约10 kg。     

A 59-year-old woman with personality change and abnormal behavior followed by amyotrophy and dementia]

We report a 59-year-old woman with generalized amyotrophy and dementia. She showed personality change at 53 years of age. When she was 56 years old, she began to show abnormal and violent behaviors. At age 58, she developed dysphagia and amyotrophy of upper limbs. She was admitted to a hospital for the treatment of aspiration pneumonia. She was severely demented and showed pseudobulbar palsy, amyotrophy of tongues, weakness of upper limbs, and pyramidal signs. She was still able to walk by herself. Dementia, pseudobulbar palsy, and amyotrophy progressed rapidly. At age 59, she became bed ridden and required tube feeding. She died by aspiration pneumonia at age 59. The patient was discussed at a neurological CPC and the chief discussant arrived at the conclusion that the patient had ALS dementia. Other possibility discussed was Pick's disease with amyotrophy. Post-mortem examination revealed severe lower motor neuron degeneration. The upper motor neurons were unaffected. Neuronal loss was not observed in the cerebral cortex, but moderate gliosis was seen in the cerebral white matter. In addition, the substantia nigra was moderately degenerated. There were ubiquitin positive neuronal inclusions in the granular cells of the dentate gyrus. Also, Bunina bodies were seen in the neurons of spinal anterior horns. These findings were characteristic pathology for ALS with dementia.     

A 57-year-old woman with progressive disturbance of gait and mental deterioration]

We report a 57-year-old woman with progressive gait disturbance and mental deterioration. She was well until March 1995, when she was 54 years of the age. At that time she noted a gradual onset of tremor and difficulty using her hand. Similar symptoms appeared in her right hands, and she visited another hospital, where 300 mg of levodopa and 7.5 mg of bromocriptine were prescribed. These medication did not help her symptoms. In the summer of 1996, she became to fall down easily. In September of the same year, she started to repeat the same words many times. She was unable to stop it. She was hospitalized to our service on January 25, 1997. On admission, she was alert but demented moderately; her Hasegawa dementia scale was 15/30. She showed palilallia, logoclonia, and echolalia. She showed constructional apraxia and questionable left-right disorientation. She had marked vertical gaze palsy with preserved oculocephalic response. She had masked face and small voice. Her gait was wide based with small steps. No muscle atrophy or weakness was noted. She showed only mild rigidity in the neck, but no rigidity was noted in the limb. No tremor was noted. She was bradykinetic. Deep tendon reflexes were symmetric and within normal limits. Laboratory findings on admission was unremarkable. MRI showed atrophy of the brain stem as well as cerebral cortical areas, particularly in the fronto-temporal region. Her hospital course was complicated with paralytic ileus and septicemia. She developed hypotension and pronounced dead on July 28, 1998. She was discussed in the neurological CPC. The chief discussant arrived at a conclusion that the patient had progressive supranuclear palsy and died of septic shock. All the participants wondered between PSP and CBD, but majority agreed with this diagnosis of the chief discussant. Only one thought that she might have had corticobasal degeneration rather than PSP, because of dementia, cortical atrophy in MRI, and lack of limb rigidity. Postmortem examination revealed cortical and brain stem atrophy. In the premotor cortex, marked astrocytosis and ballooned neurons were seen. Furthermore, astrocytic plaques were seen; this is considered to be pathognomonic for CBD. The substantia nigra showed marked neuronal loss and gliosis, but no neurofibrillary tangles or Lewy bodies were seen. Gliosis was also seen in the globus pallidus and in the medial thalamus. The pathologic diagnosis was corticobasal degeneration. This patient was very interesting case, in that the clinical manifestations appeared to be consistent with PSP, yet pathologic diagnosis was CBD. Lack of limb rigidity may be atypical for advanced PSP. In addition, palilalia appears to be more associated with CBD.     

A 54-year-old man with familial parkinsonism, gaze palsy, and dementia]

We report a Japanese man with familial parkinsonism who died at age 54. His younger brother, his mother, the mother's 4 brothers, and their mother were also affected with similar parkinsonism. The patient had had nystagmus since adolescence. He noticed difficulty in walking and micrographia at age 42. Neurological examination at age 45 in our hospital revealed pendular nystagmus, moderate rigidity in his neck and upper limbs, postural tremor in hands and shuffling gait. He received L-dopa/benzerazide 200 mg and his movement was mildly improved. Then he developed forced closing of eyelids suggesting either blepharospasms or apraxia of eye lid opening. He became apathetic at age 48. He was admitted to our hospital at age 49. On admission, he showed mild dementia and sexually disinhibited behaviours. Moderate downward gaze palsy and rigidity were seen. Increase of L-dopa/benzerazide and pergolide did not improve his parkinsonism and his disinhibited behaviors became worse. L-dopa/benzerazide and pergolide were decreased and he received electroconvulsive therapy at a psychiatric hospital with temporally improvement in his movement. He became unable to walk at age 52 and he was mutic and bedridden. He died of pneumonia at age 54. The patient was discussed in a neurological CPC, and a chief discussant arrived at the conclusion that the patient had a familial form of dementia with Lewy bodies. Many participants thought that he had frontotemporal dementia and parkinsonism linked to chromosome 17. The pathological examination of his brain showed severe neuronal loss in the substantia nigra, subthalamus, and pallidum. Ballooned neurons were observed in the cerebral cortex. Immunohistochemistry using anti-tau antibodies revealed tau-positive neurons, glial cells and threads in the cerebral cortex, white matter and subcortical nuclei; these tau deposition reacted with an anti-4-repeat tau antibody, but not reacted to an anti-3-repeat tau antibody. Sequencing of genomic DNA of the patient showed a missense mutation in exon 10 of tau that caused a substitution at codon N279K. These neuropathological and molecular studies revealed the diagnosis of the patient was FTDP-17 with N279K mutation.     

A 68-year-old man with speech disturbance as the initial symptom followed by bradykinesia and dementia. Clinical conference]

We report a 68-year-old man with progressive speech disturbance and dementia. He was well until 1995, when he noted an onset of difficulty in speech. He was able to name simple objects and understand language, however, he showed great difficulty in spontaneous speech. In 1998, he visited our service. He was alert and oriented, but he showed moderate degree of dementia. He did not appear to have aphasia but he showed marked dysarthria and slurred speech. He showed limb-kinetic apraxia in his right hand. He showed moderate restriction in his vertical gaze, masked face, and dysphagia. He walked normally. No rigidity, ataxia, or abnormal involuntary movement was noted. He showed grasp response and he was bradykinetic. He was treated with levodopa without effect. His condition deteriorated slowly and he was admitted to our service because of fever on February 13, 1999. He was alert but almost mute. He was unable to look upward or downward. Oculocephalic response was preserved. Axial rigidity was noted but no limb rigidity was present. He walked with small steps. Retropulsion was present. Deep tendon reflexes were diminished and the plantar response was flexor bilaterally. Laboratory examinations were unremarkable and his fever went down within a few days by supportive treatment. He was discharged to his home, where his condition deteriorated further. He developed cardiopulmonary arrest on May 3, 1999 and was brought into ER again. Cardiopulmonary resuscitation was unsuccessful and he was pronounced dead at 7:30 in the morning on the same day. The patient was discussed in a neurological CPC. The chief discussant arrived at the conclusion that this patient had corticobasal degeneration. But he felt that the differential diagnosis from atypical progressive supranuclear palsy, in which cortical pathology and symptoms predominated as in corticobasal degeneration, would be extremely difficult. Most of the participants felt that this patient had corticobasal degeneration, but a few thought that he had atypical PSP. Post-mortem examination revealed asymmetric cortical atrophy, which was accentuated in the left motor cortical area. Microscopic examination of the precentral cortex revealed neuronal loss and gliosis. Ballooned neurons and astrocytic plaques were also seen. The substantia nigra showed marked neuronal loss. Neuropil threads were observed in the nigra. Those threads were positive for anti-tau immunohistochemistry. The internal segment of the globus pallidus, the subthalamic nucleus, and the cerebellar dentate nucleus showed mild to moderate neuronal loss. A few neurofibrillary tangle-positive neurons were seen in these structures. Neuropil threads were also seen throughout. Pathologic changes were consistent with the diagnosis of corticobasal degeneration. One of the participants pointed out that he was able to walk at the time when he was showing marked speech disturbance and limb-kinetic apraxia, which was rather unusual for PSP suggesting corticobasal degeneration.     

Periventricular and deep white matter leukoaraiosis have a closer association with cerebral microbleeds than age

Background: Taking an advantage of the high sensitivity of 3D T2*‐weighted gradient‐recalled‐echo (GRE) imaging to cerebral microbleeds, we investigated the relationship between cerebral microbleeds and leukoaraiosis. Methods: Participants aged 40 years or more have been evaluated for the presence of cerebral microbleeds using 3D T2*‐GRE sequence since 2006. The severity of periventricular hyperintensity (PVH) and deep white matter hyperintensity (DWMH) on fluid attenuated inversion recovery images was assessed using Fazekas rating scales. Multivariate logistic regression analyses were conducted after adjustment for stroke subtype, age, PVH, DWMH, hypertension, dementia, and use of platelet aggregation inhibitors. Additionally, we examined the association between cerebral microbleeds and other covariates using a Pearson’s correlation analysis. Results: Amongst 389 patients, 67 patients had a single microbleed and 93 had multiple microbleeds. The prevalence of microbleeds was 83% amongst 53 patients with intracerebral hemorrhage (ICH), 49% amongst 173 with infarction, and 20% amongst 163 without any type of stroke. In the multivariate analyses, the odds ratio (95% CIs) of microbleed detection was 10.1, (4.12–24.8) for ICH, 2.33 (1.12–4.85) for atherosclerotic infarction, 1.66 (1.10–2.48) for PVH, and 1.49 (1.02–2.19) for DWMH. In the Pearson’s correlation analysis, cerebral microbleeds were closely related to PVH (Pearson’s correlation coefficient; 0.48) and DWMH (0.37), compared with age (0.16). Conclusions: High‐grade PVH, high‐grade DWMH, ICH, and atherosclerotic infarction were significantly independent predictors for cerebral microbleeds. In addition, we found that the grades of PVH and DWMH have a closer association with the number of cerebral microbleeds than age.     

Steroid-responsive diffuse cerebral white matter lesions in a case of intractable fungal meningoencephalitis]

We report a case of fungal meningoencephalitis with steroid-responsive diffuse cerebral white matter lesions. A 49-year-old male developed auditory hallucination, confusion and fever, on April, 1994. He was diagnosed as having cryptococcal meningoencephalitis based on the detection of cryptococcal antigens in the cerebrospinal fluid (CSF). Intravenous administration of fluconazole resulted in improvement of his neurologic symptoms and CSF findings. For the next seven months, he was treated with oral fluconazole and the neurological status was stable. However, soon after the dose of fluconazole was tapered, he became confused and febrile, which made him admitted to our hospital. Neurological examination on admission showed disturbance of consciousness, disorientation and meningeal irritation. The CSF examination revealed mild pleocytosis (mostly lymphocytes), elevated protein and normal glucose levels, although fungus was not detected. The T2-weighted image of brain MRI demonstrated diffuse hyperintense lesions in the bilateral cerebral white matters. GD-DTPA enhanced MRI showed spotty enhanced lesions in the periventricular white matters. The neurologic symptoms were once relieved after intravenous administration of fluconazole was started, but two months later, he became comatose and needed ventilatory support, despite amphotericine B therapy. Then, a needle brain biopsy targeting the white matter lesion was done. Histopathology of the specimen showed chronic inflammation with granuloma formation and T lymphycyte infiltrate around the small vessels, though fungus was not detected in the tissue. Combined therapy with corticosteroid and antifungal agents remarkably improved the neurological symptoms as well as the MRI findings. In the present case, fungal infection possibly induced an altered immune reactions which resulted in the steroid responsive diffuse cerebral white matter lesions.     

双手活动不利 行走不稳 声音嘶哑

病历摘要患者女性,19岁。主因双手活动不利4年、行走不稳3年、声音嘶哑1年,于2012年9月14日入院。患者于4年前出现双手活动不利,表现为手颤抖、不能持物,持筷或切菜时动作笨拙,不能顺利夹中或切中目标,但书写能力无明显改变。3年前出现行走不稳,行走时躯体晃动,并向一侧倾倒,     

A 96-year-old man with consciousness disturbance, convulsion, and left hemiplegia of acute onset]

We report a 96-year-old Japanese man who developed a sudden onset of left hemiplegia and coma. He was found to have diabetes mellitus, hypertension, and atrial fibrillation since 1996 with occasional episodes of congestive heart failure. He was otherwise apparently well until July 5 of 1997 when he developed a sudden onset of unresponsiveness and convulsion involving his right hand and was admitted to our hospital. On admission, his BP was 210/120 mmHg, heart rate 76/min and irregular, BT 36.5 degrees C, and Cheyne-Stokes respiration. General medical examination was otherwise unremarkable. Neurologic examination revealed semicoma, conjugated deviation to the right, loss of oculocephalic response, left facial paresis of central type, flaccid left hemiplegia, and bilateral Babinski sign. Pertinent laboratory findings are as follows: BUN 47 mg/dl, creatinine 1.46 mg/dl, GPT 69 IU/l, LDH 1,142 IU/l, and CK 385 IU/l. A chest x-ray film revealed cardiac enlargement and EKG showed left ventricular hypertrophy and atrial fibrillation. Cranial CT scan revealed low density areas involving the right anterior cerebral and the right posterior cerebral artery territories. He was treated with an intravenous osmotic agent and short course of intramuscular steroid. He remained unconscious despite these treatment and developed sudden cardiopulmonary arrest three weeks after the admission. The patient was discussed in a neurological CPC and the chief discussant arrived at the conclusion that the patient had suffered from cerebral embolism of cardiac origin. The cause of the death was ascribed to acute subendocardial myocardial infarction. Most of the participants agreed with this conclusion. Postmortem examination revealed an old subendocardial myocardial infarction involving the posterior septal region and posterolateral wall of the left ventricle. Neuropathologic examination revealed hemorrhagic infarctions involving the territories of the right anterior cerebral, right middle cerebral, right posterior cerebral, and left anterior cerebral arteries. The left A1 portion of the anterior cerebral artery was hypoplastic, and the left pericallosal artery appeared to have been receiving blood supply from the right anterior cerebral artery through the anterior communicating artery. The large arteries in the base showed marked arteriosclerosis; particularly, the initial portion of the right posterior artery showed near complete arteriosclerotic occlusions. These characteristic arterial changes appeared to be the reason why this patient suffered from an extensive infarction from what appeared to have been a single episode of cerebral embolism probably initially involving the right internal carotid artery.     

老年性血管性痴呆与脑白质疏松的相关研究

目的　探讨老年性血管性痴呆 (VD)与脑白质疏松症 (LA)的相关性。方法　对 5 4例 6 0岁以上LA患者的临床及CT和 /或MRI进行 3年跟踪观察 ,应用分级法观察LA的损伤程度 ;应用MMSE和Hachinski量表诊断VD。结果　 5 4例LA患者损伤程度Ⅰ～Ⅲ级变化分别为第 1年 34、14、6例 ,第 2年 17、19、18例 ,第 3年 8、17、2 9例。患老年性VD者第 1年 6例 ,第 2年 13例 ,第 3年 33例 ,平均年增长率为 32 %。结论　LA是老年性VD发生的早期危险信号 ,LA的损伤程度与老年性VD的发生呈正相关 (r=0 .82 ,P <0 .0 5 ) ,应当积极预防和治疗。