Elevated cerebrospinal fluid lactate levels and the pathomechanism of calcification in Fahr''s disease

In this study, we report the case of a 68-year-old man complaining of involuntary movement of his left shoulder and lower jaw plus dyspnea. On cranial computed tomography and magnetic resonance imaging, marked and symmetrical calcification at the basal ganglia and dentate nuclei was documented. An elevated cerebrospinal fluid (CSF) lactate level was confirmed by spinal tap examination and magnetic resonance spectroscopy. The raised CSF lactate level, clinical characteristics such as diabetes, bilateral hearing loss and symmetrical cerebral calcification strongly suggested some kinds of mitochondrial disease. However, gene analysis of peripheral blood leukocytes revealed no typical or known mutations. Under the diagnosis of Fahr's disease, we treated him with haloperidol, which completely abolished his symptoms. In Ellsworth-Howard test, he showed markedly decreased phosphaturic response to parathyroid hormone with same pattern as type 2 pseudohypoparathyroidism. This abnormal response in our patient, probably due to respiratory alkalosis reflecting chronic hyperventilation, might in part explain similar mechanism of ectopic calcification underlying these two diseases.     

A case of idiopathic, symmetrical non-arteriosclerotic, intracerebral calcification (Fahr's disease) associated with M-proteinemia, followed by multiple myeloma]

We described a 41-year-old woman with idiopathic, symmetrical, non-arteriosclerotic, intracerebral calcification (Fahr's disease), associated with multiple myeloma. CT scans revealed severe calcification in the basal ganglia, floors of cortices, subcortical white matter, brainstem and cerebellum without calcification in the spinal cord. Cerebral angiography showed no evidence of arteriosclerosis. The cerebral blood flow measured by SPECT, parathyroid function and calcium metabolism were within normal range. The initial symptom was dystonia and spasticity in the left leg, when she was 30 years old, followed by gait disturbance, speech impairment, micrographia and dementia. M-proteinemia was pointed out when she 32 years old. M-proteinemia, which was due to primary benign monoclonal immunoglobulinemia (PBMI), made progress slowly, followed by multiple myeloma when she was 40 years old. Periodical CT scans revealed that the intracerebral calcification had worsened gradually through 8 years. Neurological abnormality had also progressed slowly. In literature, there has not been any report about Fahr's disease associated with PBMI and multiple myeloma. Our present study is the first to radiologically prove that the intracerebral calcification in Fahr's disease progresses gradually through its course.     

A case of idiopathic brain calcification associated with dyschromatosis symmetrica hereditaria, aplasia of dental root, and aortic valve sclerosis]

The patient was a 23-year-old woman. She was the product of a full-term pregnancy and normal delivery. At age 3, she was observed to have eruptions on the face and extremities. Gait disturbance and abnormal posture appeared when she was 17-year-old. Mental deterioration followed several years later, and these symptoms progressed gradually. On examination at age 23, mixture of hyperpigmented and hypopigmented macules were observed on the face and the dorsal aspects of the extremities. We diagnosed her skin lesion as dyschromatosis symmetrica hereditaria (DSH) based on dermatological findings, normal minimal erythema dose and normal unscheduled DNA synthesis of her skin fibroblasts. Neurologically, she showed moderate mental deterioration, dystonic posture, dystonic and spastic gait, and generalized hyperreflexia. Laboratory examinations, including parathyroid function, were normal. Brain CT scan revealed severe symmetrical calcifications in the basal ganglia, cerebral white matter, and dentate nucleus. She also showed aplasia of dental root and aortic valve sclerosis. Her father also revealed the same clinical features including skin lesion, movement disorder, mental deterioration, and severe aortic valve calcification. So we diagnosed this patient as familial idiopathic brain calcification associated with DSH, aplasia of dental root, and aortic valve sclerosis. Constellation of these clinical features does not match any previously established type of familial idiopathic brain calcification or hereditary dystonia. However, Patrizi et al reported a patient with DSH associated with torsion dystonia who was very similar to our patient. We propose that our patient and the patient reported by Patrizi et al construct a distinct clinical entity in familial idiopathic brain calcification or hereditary dystonia.     

Clinical early symptoms and CT findings in Fahr syndrome

We present the results of an investigation on initial symptomatology of patients with bilateral, symmetrical intracerebral calcification of the basal ganglia (Fahr's syndrome). 62 patients, who because of various neurological or psychiatric symptoms or other reasons were referred to cranial computer-tomography, revealed clear manifestation of Fahr's syndrome. In these cases estimations of the volume of the opaque bodies were made, based on computer-integrated programmes (SO-MATOM D2). In 9 cases there was a history of thyroidectomy, on average 25 years previously. As a rule patients were referred in the age range between 40 to 60 years, those who had undergone thyroidectomy being on average somewhat older than the others. As presenting symptoms extrapyramidal syndromes, apoplexias, cephalea, affective organic alterations, alcoholism and dementia were noted. Cerebral localisation of bilateral, symmetrical calcification was most frequent in the pallidum, though this localisation may be responsible for numerous different neuropsychiatric symptoms. The dimensions of the opaque structures can be very greatly. Symptomatology seems to be practically independent of either cerebral localisation or volume, except that greater volumes of calcification seem to cause more pronounced neurological (extrapyramidal) symptomatology and dementia. The time-span between manifestation of the initial symptoms and diagnosis was shorter in neurological syndromes than in psychiatric cases. Like earlier workers, we found a high incidence (21%) of organic affective syndromes as an initial manifestation of Fahr's syndrome.     

Bilateral striopallidodentate calcification (Fahr's syndrome) and multiple system atrophy in a patient with longstanding hypoparathyroidism

Recently, a family with idiopathic brain calcification was reported, in which one family member was diagnosed with multiple system atrophy (MSA) at autopsy. We report here a case showing similar neuropathological features in a patient with longstanding hypoparathyroidism. Our female patient had a history of hypoparathyroidism with hypocalcaemia and tetany since the age of 9 years. In her 50s she developed dementia and parkinsonism. She died of myocardial infarction aged 65 years. Neuropathology showed severe brain calcifications of the Fahr type in the basal ganglia, thalami, cerebral and cerebellar white matter and dentate nuclei. Additionally, there was prominent alpha‐synucleinopathy of the multiple system atrophy type (MSA). The patient has a healthy identical twin and there is no family history of hypoparathyroidism or neurological disease. Data on alpha‐synuclein accumulation in various cases of Fahr's syndrome are needed to establish the correlation between alpha‐synucleinopathy and bilateral striopallidodentate calcification.     

Cortical deafness: demonstration of the pathologic anatomy by CT scan

A 27-year-old man with a prosthetic mitral valve had bilateral cerebral infarcts that caused a nonfluent aphasia, oral apraxia, and deafness. A computer-assisted tomographic scan showed symmetrical bilateral temporoparietal lesions. A review of the literature on other cases of cortical auditory deficits suggests that the clinical syndrome of pure word deafness in many cases is probably a less severe form of cortical deafness and is due to less extensive bilateral temporal gray matter lesions. However, strictly white matter lesions may produce some cases of either syndrome.     

An autopsied case of corticobasal degeneration with onset of nonfluent aphasia revealing symmetrical cerebral involvement

Herein we describe a patient with established corticobasal degeneration with onset of nonfluent aphasia and showing symmetrical cerebral involvement. A 64-year-old man with a speech disorder for 2 years visited our hospital. He had nonfluent aphasia (reduced spontaneous speech, loss of intonation, anomia, repetition disorder, and difficulty in speaking short sentences). He also showed right-sided motor neglect, hypertonus of the left lower limb, a mask-like facial expression, and difficulty in closing his eyes. He was restless and walked around even during examination, suggesting frontotemporal dementia (FTD). Single-photon emission computed tomography (SPECT) revealed symmetrical reduction of cerebral blood flow in the bilateral fronto-temporo-parietal lobes. His neurological condition deteriorated gradually and a year later he could not speak comprehensive sentences. Magnetic resonance imaging (MRI) of the head at age 70 showed symmetrical atrophy of the bilateral fronto-temporal lobes. He died of respiratory failure after clinical problems lasting ten years. On pathological examination, the fixed brain weighed 1,010 g and showed bilateral symmetrical atrophy of the frontal lobes. Histopathological examination revealed neuronal loss and gliosis in the frontal lobes, especially in the frontal convexity, superior frontal gyrus and precentral gyrus. Gallyas-Braak silver staining showed astrocytic plaques, argyrophilic threads and coiled bodies mainly in the frontal lobes. The substantia nigra showed severe neuronal loss on both sides and presence of free melanin. Pathological diagnosis was corticobasal degeneration (CBD). We believe that the patient had nonfluent aphasia and FTD reflected in bilateral degeneration of the frontal lobes. Some cases of CBD may present with symmetrical degeneration of the brain, even though left-hemisphere symptoms such as aphasia reveal themselves at an early stage.     

Idiopathic basal ganglia calcification presenting as hypomania

A sixty-four-year-old lady manifested a hypomanic psychosis and later developed features of a subcortical dementia and movement disorders of Parkinsonism and chorea. Computerized tomography revealed bilateral basal ganglia calcification. No evidence of parathyroid disorder or any other cause for the calcification was present. There has been only one previously reported case of organic mood disorder of a manic type presentation of idiopathic basal ganglia calcification (IBGC). The oldest reported age of onset of IBGC presenting with psychosis is 53 years and with dementia is 68 years.     

Intracranial vascular calcification with extensive white matter changes in an autopsy case of pseudopseudohypoparathyroidism

We herein report an autopsy case of a 69‐year‐old man with pseudopseudohypoparathyroidism. The patient suffered from mental retardation and spastic tetraparesis and had all the features of Albright's hereditary osteodystrophy with a normal response to parathyroid hormone in the Ellsworth–Howard test. Computed tomography demonstrated symmetrical massive brain calcification involving the bilateral basal ganglia, thalami, dentate nuclei and cerebral gray/white matter junctions, which was consistent with Fahr's syndrome. Magnetic resonance imaging revealed extensive white matter changes sparing the corpus callosum. Severe ossification of the posterior longitudinal ligament of the cervical spine was also demonstrated. A neuropathological examination revealed massive intracranial calcification within the walls of the blood vessels and capillaries with numerous calcium deposits. The calcium deposits aligned along the capillaries, and deposits in the vessel wall at the initial stage were confined to the border between the tunica media and adventitia. The vascular calcification in the basal ganglia continuously spread over the surrounding white matter into the cortex. The area of vascular calcification in the white matter was very well correlated with the area of the attenuated myelin staining. Axonal loss, myelin sheath loss and gliosis were observed in the white matter with severe vascular calcification. We should recognize the continuous area of vascular calcification and its correlation with extensive white matter changes as possible causes of neuropsychiatric symptoms in pseudopseudohypoparathyroidism with Fahr's syndrome.     

急性双侧对称性脑梗死的发病机制探讨

目的探讨急性双侧对称性脑梗死的发病机制。方法回顾性总结19例单纯位于幕上或幕下的急性双侧对称性脑梗死患者的临床及影像学资料,结合改良TOAST分型,探讨其可能的发病机制。结果急性双侧对称性脑梗死常见部位有胼胝体、分水岭区、丘脑、脑叶、脑干和小脑;其危险因素与一般脑梗死相同,部分患者可有血流动力学异常的诱因;发病机制包括血栓形成、心源性或动脉源性栓塞、低灌注、穿支动脉病以及多重发病机制的相互作用,分水岭区的双侧梗死常与低灌注有关,胼胝体、丘脑、脑干、小脑的双侧梗死应考虑到血管解剖变异存在的可能。结论急性双侧对称性梗死的发病机制复杂,相关发病危险因素或诱因、梗死灶分布以及血管检查可为探讨其发病机制提供参考依据。     

A case of bilateral perisylvian polymicrogyria with epileptic attacks of focal inhibitory seizure followed by complex partial seizure]

A 20 year-old woman began to have epileptic attacks of focal inhibitory seizure with paralysis and hypesthesia of her left or right upper limb followed by complex partial seizure several times a week since age 19. She was born by breech presentation and umbilical cord was coiling around her neck at birth. EEG showed spike foci on P 3, O1 and T5. Cerebral MRI with 4 mm-section inversion recovery image revealed bilaterally symmetrical polymicrogyria involving the posterior portion of sylvian fissure extending posteriorly to the inner cortex of the postcentral gyrus and the supramarginal gyrus, and she was diagnosed as bilateral perisylvian polymicrogyria. 99mTc-ECD SPECT showed increased cerebral blood flow over the bilateral polymicrogyric lesion. On cerebral MRA, bilateral middle cerebral arteries were narrow all way through. Epileptic attacks were controlled with zonisamide and carbamazepin. This is a rare case of bilateral perisylvian polymicrogyria because epileptic attacks were the only manifestation and the patient showed neither mental retardation nor neurological abnormality.     

A case of symmetrical aneurysms at the bilateral middle cerebral arteries associated with the deep seated arteriovenous malformation in the midline]

A case of symmetrical aneurysms at the bilateral middle cerebral arteries (MCA) associated with the deep seated arteriovenous malformation (AVM) in the midline was presented. Because symmetrical aneurysms at the MCA are 1.17% of all aneurysms, and those associated with the deep seated AVM in the midline are very rare. A 75-year-old female suffered from a sudden onset of a severe headache and a loss of consciousness, and was admitted to our department on June 14, 1996. Computed tomography(CT) showed a subarachnoid hemorrhage (SAH) in the right sylvian fissure (Fisher's Group 4). Bilateral symmetrical MCA's aneurysms and the deep seated AVM were clarified by angiography. The symmetrical aneurysms stood out anterior lateral side and the right aneurysm had bleb. On the other hand, the afferent vessels of the AVM were the branches of bilateral posterior cerebral arteries, and the efferent vessel was the vein of Galen. So we determined SAH due to right MCA aneurysm, and performed the neck clipping of the ruptured aneurysm. The symmetrical aneurysms at the MCA associated with AVM in midline have not been reported. Each parent's artery was not connected each other. These origins, therefore, are suggested to be related not only to acquired factors like hypertension, hemodynamic stress etc, but also to a congenital factor. The origin of the saccular aneurysm is suggested congenital either but it isn't definite.     

阿尔茨海默病~(18)F-FDG PET显像诊断的研究

目的 探讨阿尔茨海默病（AD）脑葡萄糖代谢及其18F-脱氧葡萄糖正电子发射计算机断层扫描（18F-FDG PET）显像的影像学特征和PET诊断标准。方法 静脉注射18F-FDG后行脑断层显像,检查13例 AD、13例非AD痴呆及13例正常人。获得纹状体、丘脑、黑质、顶叶、颞叶、额叶、枕叶、海马单位面积放射性计数与小脑计数的比值（Rcl/cb）,进行半定量分析,并与MR进行对照。结果AD患者PET异常率为100％,MR异常者占10/13。PET显像特征:①对称性双侧颞顶叶及海马伴额叶或枕叶代谢减低占9例（9/13）;②双侧颞叶对称性代谢减低伴海马或额叶代谢下降占3例（3/13）;③双顶叶对称性代谢降低1例（1/13）。12例（12/13）非AD痴呆表现为不对称、多发性代谢降低,降低区位于黑质、纹状体、丘脑及脑皮质区,MR异常率为11/13。结论 在除外脑内结构特异性损害基础上,PET发现对称性双颞顶叶、海马或颞叶、顶叶,伴或不伴枕叶、额叶代谢下降,可诊断AD。PET对AD早期诊断及鉴别诊断具有临床意义。     

Kearns-sayre syndrome with reduced plasma and cerebrospinal fluid folate

A young woman with Kearns-Sayre syndrome and progressive central nervous system deterioration over 15 years had decreased plasma and cerebrospinal fluid folate levels while receiving phenytoin for a seizure disorder. A muscle biopsy showed a “ragged red fiber” myopathy with reduced muscle carnitine and mitochondrial enzymes. Computed tomographic brain scans showed cerebral white matter hypodensities and bilateral calcification of the basal ganglia. The mechanism for the folate deficiency and altered ratio of plasma to cerebrospinal fluid folate is unknown, but the deficiency may be responsive to replacement therapy.     

Calcification of the basal ganglia: computerized tomography and clinical correlation

During a 1-year period, 4219 consecutive computerized tomograms (CT) were reviewed for basal ganglia calcification; 14 patients with such calcification were identified. Calcifications on CT scan were bilateral in 12 of these cases and unilateral in 2. All bilateral calcifications were symmetric. The globus pallidus was the site of calcification in 13 of the 14 patients. Bilateral dentate nucleus calcification was seen in one patient. Skull radiograms were normal in all but one. Patients had diverse symptoms that were often explained by other findings, suggesting that calcifications may be coincidental and that basal ganglia calcification may not be a nosologic entity. Disturbances of calcium metabolism were not found in these patients, minimizing the pathophysiologic significance of altered calcium metabolism and the need for extensive endocrinologic evaluation. The finding of basal ganglia calcification alone does not justify invasive diagnostic procedures. Extrapyramidal signs may be associated with basal ganglia calcification; parkinsonism associated with basal ganglia calcification differs from idiopathic parkinsonism in being resistant to levodopa therapy.     

~(18)F-FDG PET显像观察特发性快眼动睡眠期行为障碍患者脑葡萄糖代谢特点的研究

目的探讨~(18)F-FDG PET显像观察特发性快眼动睡眠期行为障碍(iRBD)患者脑葡萄糖代谢改变和iRBD脑葡萄糖代谢改变与病程间的相关性。方法纳入多导睡眠监测(PSG)确诊的iRBD患者20例(iRBD组)和年龄、性别匹配的健康对照者19例(对照组)。两组均行~(18)F-FDG PET脑显像。基于自动解剖标记模板将大脑划分为90个左右对称的脑区,计算各脑区葡萄糖代谢半定量值。对iRBD组和对照组各脑区葡萄糖代谢半定量值进行独立样本t检验;并对iRBD组脑葡萄糖代谢改变与病程行Pearson相关分析。结果 (1)与对照组比较,iRBD组的双侧背外侧额上回、双侧眶部额上回、双侧眶部额中回、双侧海马、双侧海马旁回、双侧杏仁核、左侧眶部额下回、左侧岛叶、左侧内侧与旁扣带脑回、左侧中央旁小叶、左侧苍白球的葡萄糖代谢半定量值均增高(P0.05);双侧距状裂周围皮质、双侧楔叶、双侧舌回、双侧枕上回、双侧枕中回、双侧枕下回、双侧角回、双侧颞上回、双侧颞中回、右侧颞横回的葡萄糖代谢半定量值均降低(P0.05)。Pearson相关分析结果,iRBD组双侧杏仁核、双侧颞上回、右侧楔叶、右侧枕上回、右侧颞横回、左侧海马、左侧颞中回的葡萄糖代谢半定量值与病程呈正相关(P0.05);而双侧眶部额上回、双侧眶部额中回、左侧中央旁小叶、左侧眶部额下回、左侧内侧和旁扣带回、右侧背外侧额上回、右侧海马旁回的葡萄糖代谢半定量值与病程呈负相关(P0.05)。结论 iRBD患者脑内存在疾病相关的葡萄糖代谢水平改变,有助于客观评估iRBD病情的变化。     

Analysis of Gene Expression Pattern and Neuroanatomical Correlates for SLC20A2 (PiT-2) Shows a Molecular Network with Potential Impact in Idiopathic Basal Ganglia Calcification (“Fahr’s Disease”)

Familial idiopathic basal ganglia calcification (FIBGC), also known as “Fahr’s disease,” is a neuropsychiatric disorder with motor and cognitive symptoms. It is characterized pathologically by bilateral calcification most commonly in the basal ganglia and also in other brain regions such as the thalamus and cerebellum. A recent report by Wang et al. (2012) discovered multiple families with FIBGC carrying mutations in the SLC20A2 gene, encoding the inorganic phosphate transporter PiT-2, which segregated in an autosomal dominant pattern. To understand further the role of SLC20A2 in FIBGC brain pathology, here we described the gene expression pattern across the whole brain for SLC20A2, using the Allen Institute Human Brain Atlas database. Microarray analysis provided evidence that the neuroanatomical pattern of expression for SLC20A2 is highest in the regions most commonly affected in FIBGC. Neuroanatomical regions that demonstrated high correlation or anti-correlation with SLC20A2 expression also showed a molecular network with potential to explain the limited neuroanatomical distribution of calcifications in IBGC. Lastly, these co-expression networks suggest additional further candidate genes for FIBGC.     

Striopallidodentate Calcification and Progressive Supranuclear Palsy-Like Phenotype in a Patient with Idiopathic Hypoparathyroidism

We present a 77-year-old woman with levodopa-nonresponsive parkinsonism, dementia, and supranuclear gaze palsy on vertical and horizontal gaze. Laboratory findings were consistent with idiopathic hypoparathyroidism, and brain computed tomography showed extensive bilateral calcifications of the basal ganglia, centrum semiovale, dentate nuclei, and cerebellar white matter. These results illustrate that striopallidodentate calcification due to hypoparathyroidism may present with symptoms mimicking progressive supranuclear palsy.     

获得性肝脑变性的临床与影像学特点

目的分析获得性肝脑变性的临床和影像学特征，探讨其规律性。方法分析9例获得性肝脑变性病例的临床表现、实验室检查和影像学改变的数据。结果5例既往有明确的肝硬化病史，4例没有明确的肝病病史，发病后检查分别发现肝血管病、肝胰脾等弥漫钙化或者肝硬化。主要临床表现为：精神异常、认知能力下降、帕金森病样综合征、构音障碍、共济失调、睡眠障碍。肝酶学轻中度异常，而血氨均升高。脑电图提示脑电活动呈弥漫性减慢，4例出现三相波节律。影像学改变为苍白球、大脑脚、小脑和大脑皮层下对称性短T1加权像信号，以及基底节、中脑、脑桥、延髓橄榄核对称性长T2加权像信号。结论获得性肝脑变性是肝细胞和肝血管病变引起的神经功能损害综合征，肝酶改变、血氮升高和脑电图符合代谢性疾病改变，结合特征性影像学改变，对疾病的诊断具有重要意义。     

Electroencephalographic and Magnetic Resonance Correlations in Children with Intractable Seizures of Lennox-Gastaut Syndrome and Epilepsia Partialis Continua

Summary: A study was performed of EEG-magnetic resonance imaging (MRI) abnormalities in 7 Lennox-Gastaut syndrome (LGS) children and 3 epilepsia partialis continua (EPC) children with intractable generalized and partial motor seizures, respectively. In 4 children with LGS and 3 children with EPC, depth electrodes were implanted in the centromedian thalamic nuclei (CM) for seizure control. In all children with LGS, hyperdense, T₂-weighted MRI signals were observed at the mesencephalic level of the brainstem, whereas none of the 3 children with EPC had this finding. Patients with idiopathic LGS without cerebral hemisphere MRI abnormalities showed generalized bilateral and symmetrical spike-wave EEG activity. Patients with symptomatic LGS with unilateral hemispheric MRI abnormalities demonstrated asymmetrical EEG activity with higher amplitude spike-and-wave over the normal hemisphere. Patients with EPC with unilateral hemispheric lesions had lateralized higher amplitude spike-wave over the damaged hemisphere. These data suggest that abnormal mesencephalic MRIs are a sign of bad prognosis in patients with LGS but not with EPC. Maximal amplitude paroxysmal EEG activities may indicate the abnormal hemisphere in patients with EPC or the normal hemisphere in those with LGS.