Cerebral Whipple's disease with a stroke-like presentation and cerebrovascular pathology

Although neurological symptoms are common in Whipple's disease, patients rarely have a purely neurological presentation and involvement restricted to the central nervous system is uncommon. A 39 year old woman presented with a meningoencephalitic illness, which responded to penicillin. Eleven months later she developed recurrent stroke-like episodes. Patchy enhancing meningeal, cortical, and subcortical lesions thought to be vascular in origin developed within nine days of the onset of symptoms. No evidence was found of a cardiovascular source of emboli, vasculitis, or thrombophilic condition. A brain biopsy showed meningoencephalitic features suspicious of Whipple's disease associated with leptomeningeal arterial fibrosis and thrombosis. DNA polymerase chain reaction confirmed Tropheryma whippelii in both blood and brain tissue. The neurological manifestations of cerebral Whipple's disease are varied and very rarely include stroke-like symptoms. The pathogenesis of cerebral infarction in Whipple's disease is not well established but arterial fibrosis and endocarditis complicated by embolisation have been reported. This case emphasises the importance of early brain biopsy in unusual cases of stroke and illustrates the clinical utility of polymerase chain reaction to confirm Whipple's disease.     

Transiente kortikale Blindheit bei EPH-Gestose infolge zerebraler Vasospasmen

The pathogenesis of cortical blindness as a rare complication in severe preeclampsia is still unclear. The case of a women with postpartum blindness is reported in which CT and MRI initially showed cortical and subcortical edema in the parieto-occipital lobes. At this time cerebral angiography and transcranial color-coded sonography (TCCS) revealed widespread cerebral vasospasm. Mean blood flow velocities in the middle and posterior cerebral artery and carotid syphon initially reached 380 cm/s and normalized within 2 weeks. While the patient's vision improved rapidly, follow-up MRI disclosed ischemic lesions and petechial hemorrhage in the occipital cortex. This case provides rare documentation that transient blindness in patients with preeclampsia may result from parieto-occipital ischemia due to cerebral vasospasm. In such patients TCCS may be useful to detect vasospasm associated with preeclampsia/eclampsia.     

A case progressive dementia developed after repeated head trauma

A 46-year-old man who developed progressive dementia after repeated head trauma was reported. At the age of 30 and 36, he encountered traffic accidents and suffered from blows to his head. At 37 years old, he noticed impairment of memory and comprehension. At 41 years old, he was observed to become easily angered. These symptoms were slowly progressive, and at age 46 he was examined by us. He had no particular family history of dementia. Neurological examination revealed a disturbance of cognitive ability. The brain CT and MRI showed marked atrophy of the cerebral cortex, especially in the frontal and temporal lobes without any demonstrable lesions in the white matter. A single photon emission computed tomography (SPECT) using inhalation of 133Xenon disclosed hypoperfusion of the cerebral blood flow localized in the bilateral frontal and parietal lobes. He was supposed to suffer from juvenile Alzheimer's disease which might have developed after repeated head trauma. One similar case had been reported as a posttraumatic premature Alzheimer's disease. Finally, we discussed other causes of dementia including metabolic, infectious and vascular diseases. The present case also suggests that head trauma might be one of the provoking or promoting factors of Alzheimer's disease.     

Distribution of cerebral cortical lesions in Pick's disease with Pick bodies: a clinicopathological study of six autopsy cases showing unusual clinical presentations.

We investigated six Japanese autopsy cases of Pick's disease with Pick bodies (PDPB) both clinically and pathologically, and examined the distribution of their cerebral cortical lesions using hemisphere and/or bisphere specimens. The lesions were classified into three categories (slight, moderate, and severe). Two patients with a clinical diagnosis of primary progressive apraxia and of slowly progressive aphasia had speech apraxia as their initial signs, and the other two patients were suspected as having Alzheimer's disease, with the clinical diagnosis of the remainder two patients being presenile dementia and depression, respectively. Extrapyramidal signs, believed to be rare in PDPB, were present in four patients. Severe lesions were multicentrically present in the cerebral cortices of all six cases. In two patients with speech apraxia, severe lesions were seen in the primary motor area, which generally has not been regarded as an "atrophic center" in Pick's disease. Furthermore, in a patient with depression, severe lesions were more widespread in the convexity than in the orbital region of the frontal lobe. The parietal lobes, including the postcentral gyrus usually believed to be spared in Pick's disease, were severely involved in three patients. We postulate that the clinical features of PDPB have a much wider spectrum than previously believed. In addition, we believe that the distribution of the cerebral cortical lesions in PDPB is more widespread than previously assumed, and that clinical manifestations of PDPB depend to some extent on the topographic distribution of the cerebral cortical lesions.     

Superior sagittal sinus thrombosis as a rare complication of spontaneous intracranial hypotension syndrome: a case report and review of the literature

In addition to an orthostatic headache, spontaneous intracranial hypotension syndrome can lead to subdural hematoma and diffusion, subarachnoid hemorrhage, and brain sag. However, cerebral venous sinus thrombosis is rarely reported in patients with spontaneous intracranial hypotension. We present the case of a 35-year-old male who developed an orthostatic headache, nausea, vomiting, and photophobia for 5 days. An enhanced brain magnetic resonance image showed extensive linear pachymeningeal enhancement in the bilateral cerebral hemispheres. Lumbar puncture showed that cerebrospinal fluid pressure was 80 mmH₂O. Subsequent magnetic resonance scans demonstrated subdural effusion of the bilateral frontoparietal lobes, hyperintense T1-weighted images, and T2WI lesions within the superior sagittal sinus in 17?days. The patient was given low molecular weight heparin and adverse events occurred. Head computed tomography showed cerebral external fluid accumulation in the bilateral frontoparietal lobes. Then, digital subtraction angiography was performed at 22?days, which confirmed superior sagittal sinus thrombosis, and the patient recovered fully after therapy. The evolution of the disease and radiological findings support the diagnosis of spontaneous intracranial hypotension with superior sagittal sinus thrombosis. To the best of our knowledge, there are very few case reports describing superior sagittal sinus thrombosis as a complication of spontaneous intracranial hypotension. When spontaneous intracranial hypotension and cerebral venous thrombosis occur together, difficult practical questions arise regarding the treatment of these two conditions.     

Whipple's disease of the central nervous system

Summary Whipple's disease presenting as a neurological disease without gastrointestinal symptoms is an unusual occurrence. A 40 year old man suffered hypersomnia, memory loss and progressive ophthalmoplegia for 6 months prior to death. The nature of his disease was not established during life. Extensive granulomatous inflammation affecting the hypothalamus, hippocampus and periaqueductal gray matter of the brain was found to represent Whipple's disease by electron microscopy. Characteristic lesions were also present in spleen, mesenteric lymph nodes, small intestine and myocardium. Bacillary bodies and membranous inclusions similar to those seen in visceral lesions of Whipple's disease were present in macrophages. The findings supported the theory of direct involvement of the central nervous system by bacilli rather than a metabolic origin for the lesions.     

Distribution of cerebral cortical lesions in diffuse neurofibrillary tangles with calcification: a clinicopathological study of four autopsy cases showing prominent parietal lobe involvement

We investigated clinicopathologically four Japanese autopsy cases of diffuse neurofibrillary tangles with calcification (DNTC), which has been believed to be characterized by temporal or temporofrontal circumscribed lobar atrophy, and examined the distribution of their cerebral cortical lesions using hemisphere specimens. The lesions were classified into three categories (slight, moderate, and severe). Severe lesions were present in the temporal lobes and insular gyri of all four cases, consistent with the studies reported to date. In contrast, severe lesions were encountered in the parietal lobe of case 1 and moderate lesions were found in the parietal lobes of cases 2–4. Furthermore, moderate lesions of the precentral gyrus were present in cases 2–4, and moderate lesions of the postcentral gyrus were encountered in all four cases. We postulate that the distribution of cerebral cortical lesions in DNTC is more widespread than previously assumed. Our data also indicate that the unusual clinical signs of DNTC reported by several Japanese researchers, including parietal signs such as apraxia and agnosia, are roughly consistent with the topographic distribution of cerebral cortical lesions in DNTC elucidated in this study.     

MRI findings in a case of prolonged status epilepticus

We report the MR imaging findings in a 20 year old woman with status epilepticus of more than 3 months duration following an episode of lymphocytic meningitis. Repeated MR examinations showed progressive symmetrical cortical lesions, followed by subcortical and basal ganglia lesions which evolved to cortical laminar necrosis and hemorrhagic necrosis with eventual subcortical cerebral atrophy. This case has similarities with animal status epilepticus models. Biological investigations were all negative. This suggests that the brain lesions may be related to the prolonged status epilepticus.     

Frequent Hemorrhagic Lesions in Cerebral Toxoplasmosis in AIDS Patients

Cerebral toxoplasmosis is a frequent complication in immunosuppressed patients such as AIDS (acquired immunodeficiency syndrome). Frequently, lesions are located deep in the brain which are inaccessible for biopsy making rapid diagnosis dependent on accurate interpretation of neuroimaging findings. The commonest cranial CT findings reported in toxoplasmosis are ring enhancing hypodense lesions in basal ganglia or cortical gray matter. Hemorrhage has only rarely been described and is usually seen following antitoxoplasma treatment. We reviewed the records of 11 AIDS patients with cerebral toxoplasmosis and found multiple hemorrhagic cerebral, cerebellar, or brain stem lesions in 7 of 11 patients. Six patients had hemorrhage at the time of initial clinical presentation and one developed hemorrhage following 2 weeks of antitoxoplasma treatment. We conclude that hemorrhagic lesions are frequently found on cranial MRI scans in cerebral toxoplasmosis. AIDS patients presenting with hemorrhagic cerebral lesions should be considered for a trial of presumptive antitoxoplasma treatment.     

Cognitive dysfunction in a patient with brainstem hemorrhage

A 54-year-old, right-handed male suffered sudden onset of vertigo and vomiting. He was diagnosed with brainstem hemorrhage, and treatment was administered. After the vertigo improved, he showed disturbance of attention and anterograde amnesia. Magnetic resonance imaging revealed a hematoma across the pons on both sides, but no lesions were obvious in the cerebellum or the cerebrum. Single photon emission tomography showed decreased perfusion not only in the brainstem but also in the bilateral frontal and temporal lobes. Amnesia and executive dysfunction decreased in the 8 months following the stroke onset, with improvement in regional cerebral blood flow to the frontal and temporal lobes. These findings suggest that a hemorrhage in the pons caused diaschisis resulting in a secondary reduction of activity in the cerebral cortex and the occurrence of cortical symptoms.     

Whipple''s disease confined to the CNS presenting with multiple intracerebral mass lesions.

A patient with isolated cerebral Whipple's disease presented with signs of raised intracranial pressure and multiple ring enhancing intracerebral mass lesions evident on CT and MRI imaging. Characteristic intracellular bacilliform inclusions were identified in a brain biopsy. Clinical improvement followed treatment with parenteral antibiotics for two weeks and long term sulphamethoxazole-trimethoprim. As CNS relapse of Whipple's disease may occur after several years, long term treatment should include antibiotics that are able to cross the blood-brain barrier.     

Novel Neuroimaging Findings in a Patient with Cerebral Whipple''s Disease: A Magnetic Resonance Imaging and Positron Emission Tomography Study

The authors report a 43-year-old patient with histopathologically proven cerebral Whipple's disease. Magnetic resonance imaging (MRI) revealed a multilayered left frontal lesion without mass effect, no perifocal brain edema, no contrast enhancement, and a thin shell of fluid signal that presented as an incomplete, open ring. An [11C]methionine positron emission tomography (PET) study showed low uptake below the threshold that is characteristic for brain tumors. In precise co-registration to the MR images, the PET data showed that increased uptake was mainly located in the direct adjacent part of the MRI lesion. The fluid signal on MRI corresponded to the extensive outflow of fluid from the lesion, which was observed during neurosurgical resection, and also to the neuropathological findings. The authors conclude that this cerebral manifestation of Whipple's disease made a unique and hitherto undescribed appearance on MRI; uptake pattern of PET amino acid tracer may help in the preoperative distinction of inflammatory from neoplastic lesions.     

A case of reversible postpartum cytotoxic edema in preeclampsia

We report on a 32-year-old woman who developed reversible cortical blindness and right-sided weakness after cesarean section at 36 weeks of gestation, due to preeclampsia. An initial brain MRI demonstrated high signal intensity lesions in the bilateral occipito-parietal and left frontal lobes on T2-weighted and diffusion-weighted imaging. All of the lesions showed low signal intensity on apparent diffusion coefficient (ADC) map, which were compatible with cytotoxic edema, and MR angiography (MRA) showed diffuse vasospasm of the intracranial vessels. A follow-up brain MRI showed that most of the lesions disappeared and the vasospasm also resolved. This case suggests that the cytotoxic edema in preeclampsia may evolve differently from the pattern in cerebral infarction and explains the relatively benign course of the neurological signs in preeclampsia.     

Whipple''s disease confined to the brain: a case studied clinically and pathologically

A 40 year old man developed seizures, intermittent fever, and progressive dementia ending in coma and death after four years. The cerebrospinal fluid showed variable pleocytosis and occasional elevation of protein. The necropsy revealed many lesions characteristic of Whipple's disease confined to the grey matter of the brain. The pathological changes were studied with the light and electron microscope. The findings permitted an understanding of the temporal sequence of changes in the lesions. Involvement of the brain in this condition is rare, but the disease is treatable and the diagnosis can be made by brain biopsy.     

Dutch hereditary cerebral amyloid angiopathy: Structural lesions and apolipoprotein E genotype

Hereditary cerebral hemorrhage with amyloidosis-Dutch type is caused by a mutation at codon 693 of the β amyloid precursor protein gene. The disease is clinically characterized by strokes and dementia. In addition to cerebral plaques, cerebral amyloid angiopathy is the pathological hallmark. We investigated the correlation between radiological (white matter hyperintensities and focal lesions on magnetic resonance images) and pathological lesions (cerebrovascular amyloid angiopathy and plaques) and the apolipoprotein E genotype in patients with the disease. Twenty-five patients were studied using magnetic resonance imaging, and brain tissue from 8 patients was studied histopathologically. Neither the white matter hyperintensity scores nor the number of focal lesions on magnetic resonance images were associated with the presence of an ?4 allele. Nor was a correlation found between the number and type of plaques and the apolipoprotein E genotype. All patients had severe amyloid angiopathy in all cortical areas investigated. This study showed that the apolipoprotein E genotype does not modulate amyloidrelated structural lesions in hereditary cerebral hemorrhage with amyloidosis of the Dutch type.     

Progressive degeneration of the cerebral cortex in infancy

Summary The clinical and pathological features of a case with primary progressive degeneration of the cerebral cortex are presented. Two siblings had nearly identical clinical histories. All three children were born microcephalic and they died at the age of 7, 10 and 18 months, respectively. All showed progressive mental and motor deterioration. Myoclonus and attacks of opisthotonus were prominent features. Postmortem examination was performed in the third child, who died at the age of 10 months. The brain weight was 310 g. The cerebral cortex was severely atrophic, with extensive laminar neuronal loss. The cerebellum was normal. The optic tracts were atrophic. Neuronal loss was observed also in a few other systems but their relation to the primary disease is uncertain. The basal ganglia were normal and the hippocampus showed only slight nerve cell loss.The case is considered to belong to a small group of cases with primary progressive cortical degeneration described by Laurence and Cavanagh (1968). This group should be distinguished from cases with secondary cortical degeneration caused by anoxic damage from recurrent epileptic attacks. The primary cortical degeneration may start shortly before birth, or after a brief periood of normal postnatal development. A positive family history has been reported in most cases, suggesting an inherited metabolic defect as cause of the disease.     

Meningo-ependymitis in Whipple's disease

Six years after apparent complete recovery from intestinal Whipple's disease, a 56 year old man developed insidious progressive somnolence and gait ataxia. Studies showed hydrocephalus with obstruction of the aqueduct and CSF leukocytosis and elevated protein. Arachnoid biopsy during craniotomy revealed chronic inflammatory infiltration with PAS-positive macrophages. The patient died 5 years later despite two courses of antibiotic therapy. This is the first report of histologically confirmed cerebral Whipple's disease during life. Whipple's disease is a systemic infectious disorder. Cerebral involvement even in neurologically asymptomatic patients should be sought with periodic CSF cytologic studies and a search for hydrocephalus. The possibility of cerebral Whipple's disease should be considered in the presence of unexplained hydrocephalus and/or chronic inflammatory changes in the spinal fluid, especially in those with past or active intestinal disease.     

脑淀粉样血管病的影像学标志物及临床相关性研究进展

脑淀粉样血管病（cerebral amyloid angiopathy,CAA）是一种多见于老年人群中的脑小血管病, 不同于高血压导致的脑小血管病易累及脑深部区域,CAA多累及皮层及软脑膜小血管。多发脑叶微出 血是CAA患者常见的影像学表现,研究认为其与症状性脑叶出血及进行性认知功能下降相关。随着 近年来对脑小血管病影像学表现的深入研究,发现皮层蛛网膜下腔出血与皮层表面含铁血黄素沉 积是CAA相对特异的影像学表现,并且与短暂性局灶性神经系统症状发作相关。此外,脑白质高信号、 小梗死灶等脑小血管病影像学标志均在CAA患者中出现,提示除外临床较关注的出血性改变,CAA患 者的缺血性损伤也是导致临床症状的重要因素。     

Primary progressive apraxia

Similar to primary progressive aphasia, primary progressive apraxia has been considered to cause slowly progressive apraxia without dementia and to be a dependent disease. Of the 3 cases reported by De Renzi in 1986, 1 case showed slowly progressive apraxia without dementia. Since then, cases of primary progressive apraxia have been reported occasionally. Studies on primary progressive apraxia indicate that not only focal lesions caused by vascular disease or brain trauma but also lesions caused by neurodegenerative disease can cause apraxia alone, thereby supporting the hypothesis that apraxia-associated neurodegeneration may develop in cases of primary progressive apraxia. The pathogenesis of primary progressive apraxia is yet to be elucidated. Clinical features of primary progressive apraxia are not precisely distinguishable from those of corticobasal degeneration (CBD); further, previous studies have indicated that the brain pathology observed in primary progressive apraxia is consistent with that in Alzheimer disease (AD) or Pick disease. "Primary" progressive apraxia may be intrinsically different from slowly progressive apraxia that is associated with CBD, AD, or Pick disease and may show specific pathological findings. On the other hand, primary progressive apraxia may not be a dependent disease but a syndrome characterized by prolonged neurodegeneration that is observed in various degenetive dementias such as CBD, AD, or Pick disease.     

Slowly progressive dysarthria and impaired language function--a case report]

A 68-year-old right-handed woman was admitted to Tokyo Metropolitan Geriatric Hospital because of slowly progressive dysarthria and writing disability over 2-year period. On admission, severe dysarthria was observed, but no dysphagia. The dysarthria mostly resembled a type of pseudobulbar palsy, although it was associated with effortful speech production. An oro-facial apraxia was also found. She could name objects, and could understand spoken words correctly. Examination using the Western Aphasia Battery showed diminution of word fluency, impaired repetition and perseveration and writing errors. On the Wechsler Adult Intelligence Scale-R verbal IQ was 100 and performance IQ was 87. These scores did not suggest any significant degree of general intellectual deterioration. Wisconsin card sorting test disclosed mild frontal dysfunction. Magnetic resonance imaging showed cortical atrophy in the bilateral frontal and temporal lobes. Measurements of regional cerebral metabolic rate by 18F-FDG-PET demonstrated decreased uptake in the latero-dorso-inferior area of the bilateral frontal lobes, especially on the left side. The present case showed slowly progressive dysarthria and progressive aphasia without generalized dementia, and without typical aphasia. These symptoms are speculated to be related to the atrophy in the bilateral frontal and temporal lobes shown by MRI and the decreased metabolic rate in the left dominant bilateral frontal lobes on PET study. The pathologic process responsible for these lesions remains obscure.