线粒体脑肌病的临床与神经影像学(附12例分析)

目的　分析线粒体脑肌病病人的临床表现及神经影像学特点 ,以便早期诊断。方法　对 12例确诊线粒体脑肌病的病人进行回顾性研究。结果　抽搐、运动耐受差、智能障碍为本病的主要临床表现 ;脑叶病灶、基底节区为主的幕上多发病灶、脑萎缩为本病的主要神经影像学特点。结论　具有上述复合临床表现及神经影像学改变者 ,应考虑线粒体脑肌病的可能     

Sellar abnormalities in female first-degree relatives

Non-pituitary lesions account for a minority of sellar region abnormalities. We report the unusual occurrence of non-pituitary sellar/suprasellar lesions in a mother and her two daughters. Each of these cases was diagnosed and managed differently, illustrating the relative importance of radiographic imaging, tumor markers and histopathologic examination in the diagnosis and treatment of intracranial disease. The mother had histologically confirmed Rathke's cleft cyst (RCC) with typical radiographic and histologic appearance. One daughter was treated presumptively for germinoma based on characteristic radiographic studies and slightly elevated tumor marker. The other daughter's lesion exhibited radiographic characteristics concerning for pituitary macroadenoma but with slightly elevated germ cell tumor marker, raising the suspicion for germinoma. Biopsy of the intrasellar mass revealed only proteinaceous material and normal anterior pituitary, consistent with cyst content without evidence of neoplasm. Without a clear unifying diagnosis it is difficult to posit an underlying pathology or genetic mechanisms in this unusual set of cases. At least two of the patients had benign cysts. The diagnosis of the third patient is unclear as there was no tissue biopsy. However, it is highly improbable that three female first-degree relatives would develop such lesions in the same brain region simply by chance.     

Cervical syringohydromyelia secondary to chronic supratentorial subdural hematoma

Introduction: Syringohydromyelia associated with supratentorial space-occupying lesion has rarely been reported. We present a 28-year-old woman was admitted to the hospital with head and neck pain. Upon examination, there was only left central facial paralisia, with no evidence of papilledema. Methods and Results: Cranial magnetic resonance imaging (MRI) revealed a left parietal and temporal chronic subdural hematoma (CSH) with a 1-cm shift to the right from midline. Also, cervical MRI revealed a syringohydromyelic cavity at the level of C6/7. The patient was operated on for supratentorial CSH. A follow-up cervical MRI revealed no syringohydromyelic cavity after 2 months. No neurological deficit was reported, and overall outcome was excellent. Conclusion: Syringohydromyelia was secondary to a space-occupying lesion in our case of supratentorial chronic subdural hematoma.     

Multiple supratentorial hemangioblastomas following primary infratentorial manifestation

A case of multiple supratentorial hemangioblastomas combined with a primary cerebellar manifestation is reviewed. There was no association with polycythemia or von Hippel-Lindau syndrome. The authors emphasize neuropathological and neuroradiological methods in detecting this rare disease.     

CT and MRI aspects of supratentorial hemispheric tumors of childhood and adolescence

The neuroradiological features of supratentorial hemispheric tumors (SHTs) were studied in 27 patients whose ages ranged from 11 months to 18 years. Astrocytomas constitued 10 of the 27 SHTs. On computed tomography low-grade astrocytomas were in most cases hypodense; after intravenous administration of contrast medium, pilocytic astrocytomas enhanced, whereas fibrillary astrocytomas did not. Gd-DPTA-enhanced magnetic resonance imaging was the most useful technique for the assessment of recurrences. Atypical imaging features were observed in one glioblastoma and in oligodendrogliomas (in half of the cases no calcifications were found). Gangliogliomas were surprisingly rather frequent in our series (5/27) and appeared in three cases as low-density, well-circumscribed lesions, not calcified and without edema and mass effect, while in two cases they had pronounced perifocal edema without clear demarcation. A rare desmoplastic infantile ganglioglioma was observed. The two meningiomas showed malignant behavior.     

MRI gadolinium enhancement precedes neuroradiological findings in acute necrotizing encephalopathy

We report a 2-year-old Japanese boy with acute necrotizing encephalopathy (ANE) triggered by human herpes virus-6, who presented insightful magnetic resonance imaging (MRI) findings. He was admitted due to impaired consciousness and a convulsion, 2 days after the onset of an upper respiratory infection. At admission, cranial MRI showed marked gadolinium enhancement at the bilateral thalami, brainstem and periventricular white matter without abnormal findings in noncontrast MRI sequences. On the following day, noncontrast computed tomography demonstrated homogeneous low-density lesions in the bilateral thalami and severe diffuse brain edema. The patient progressively deteriorated and died on the 18th day of admission. The pathogenesis of ANE remains mostly unknown, but it has been suggested that hypercytokinemia may play a major role. Overproduced cytokines cause vascular endothelial damage and alter the permeability of the vessel wall in the multiple organs, including the brain. The MRI findings in our case demonstrate that blood–brain barrier permeability was altered prior to the appearance of typical neuroradiological findings. This suggests that alteration of blood–brain barrier permeability is the first step in the development of the brain lesions in ANE, and supports the proposed mechanism whereby hypercytokinemia causes necrotic brain lesions. This is the first report demonstrating MRI gadolinium enhancement antecedent to typical neuroradiological findings in ANE.     

Genetics of cerebral cavernous angioma

Cerebral cavernous malformations (CCM) are hamartomatous vascular anomalies characterized by densely packed, grossly enlarged immature capillaries without intervening neural tissue. Depending on their location and size (ranging from a few millimeters to several centimeters), the biologically dynamic lesions become symptomatic during the second to fourth decade of life. Clinical symptoms include recurrent headaches, seizures, intracranial hemorrhage, and stroke. There are sporadic and autosomal dominantly inherited forms of CCM. Causal mutations have been demonstrated in three genes, KRIT1, MGC4607, and PDCD10, but additional genes are likely to be discovered. These genes are therefore thought to play a role in angiogenesis. Their specific modes of actions, their contribution to and their likely penetrance in the genesis of CCM are the subject of current investigations. Genetic counseling is strongly advisable for patients with a positive family history and for seemingly sporadic cases with multiple lesions, and genetic testing should be considered on an individual basis. The identification of a mutation enables precise genetic testing of relatives. Given the 50 % a priori risk of autosomal dominant inheritance, the benefits of genetic testing are twofold: a positive test result in a presymptomatic carrier permits close neuroradiological surveillance and timely neurosurgical intervention; a negative test result relieves the proband of unwarranted anxiety and unnecessary medical supervision.     

Disseminated Diffuse Sclerosis; A Variety of Multiple Sclerosis with Characteristic Clinical,Neuroimaging, and Pathological Findings

A 20-year-old man had a subacute onset of frontal lobe findings and seizures. Computed tomography and magnetic resonance imaging showed three large lesions with mass effect and ring enhancement. Histology and biochemistry confirmed a demyelinating process similar to myelinoclastic diffuse sclerosis but with multiple, noncontiguous lesions. This variety of multiple sclerosis (MS) with clinical, neuroimaging, histological, and treatment characteristics different from typical MS could be termed disseminated diffuse sclerosis.     

Schilder’s disease: non-invasive diagnosis?

Schilder’s disease, or myelinoclastic diffuse sclerosis, is a rare disorder characterised by an inflammatory white matter plaque of demyelination. Clinical signs and symptoms might be atypical for early multiple sclerosis and at imaging the lesion is easily taken for a brain tumour. Regardless of the use of Poser’s criteria for clinical diagnosis of Schilder’s disease proposed in 1986, diagnostic difficulties are still present, as evidenced by the many reported cases in the English literature revised (Pubmed indexed, period 1998–2008). It clearly emerges that neuroradiological features, observable in additional magnetic resonance sequences are crucial, besides the consideration of Poser’s criteria, in differentiating between demyelinating lesions and brain tumours. A 29-year-old female patient is presented, where a careful evaluation of both the clinical and radiological features, which might have been at a first glance misleadingly suggestive for a brain tumour, allowed non-invasive diagnosis of Schilder’s disease.     

Disappearance of hypointense multiple sclerotic lesions on FLAIR MRI.

A child is presented who displayed hypointense multiple sclerotic lesions on fluid-attenuated inversion recovery sequences by magnetic resonance imaging, with the possible pathologic tissue changes of these hypointense lesions evaluated. The magnetic resonance imaging results in this patient demonstrated the disappearance of low-signal lesions on fluid-attenuated inversion recovery in multiple sclerosis, and the improvement of this patient's condition was likely compatible with sequential magnetic resonance imaging findings. Some hypointense lesions in the supratentorial white matter that appear on fluid-attenuated inversion recovery images in multiple sclerosis patients may include reversible brain lesions, suggesting extracellular fluid collection not accompanied by axonal loss or gliosis.     

Imaging brain damage in first-degree relatives of sporadic and familial multiple sclerosis

OBJECTIVE: Our objective was to assess brain damage in first-degree relatives of patients with sporadic and familial multiple sclerosis (MS). METHODS: Asymptomatic first-degree relatives of sporadic (sMS, n = 152) and familial MS (fMS, n = 88) and healthy volunteers (NC, n = 56) underwent brain MRI and magnetization transfer (MT) imaging on a mobile MR scan. On MR examinations, we visually assessed white matter (WM) lesions and quantified WM lesion volumes, brain volumes, and MT ratio (MTr) in lesions and normal-appearing WM (NAWM). RESULTS: A lesional MR pattern similar to that of MS patients was found in 4% sMS and 10% fMS. In these WM lesions, MTr was lower (p < 0.0001) than in the WM of NC. In contrast, there was no difference in NAWM-MTr and brain volume values between the three groups. INTERPRETATION: Focal brain abnormalities indistinguishable from those of MS occur in asymptomatic first-degree relatives of MS patients. These are twice more frequent in fMS than in sMS but do not lead to the widespread tissue damage commonly found in MS patients. Although there is a genetic susceptibility to develop brain abnormalities suggestive of focal demyelination in first-degree relatives of MS patients, other factors are probably critical for the development of a diffuse, clinically relevant, pathology.     

Familial multiple sclerosis: volumetric assessment in clinically symptomatic and asymptomatic individuals.

A genetic basis for clustering of multiple sclerosis (MS) cases, based on studies of MS families, has been proposed for decades. Few reports provide detailed neurological as well as neuroradiological findings on these patients. We report total T2-weighted intracranial lesion volumes on members of three familial MS cohorts: a mother and father with conjugal MS with one affected son and a neurologically normal son and daughter, one pair of monozygotic twin sisters with MS, and a female sibling pair with MS. We hypothesized that asymptomatic siblings in a family with two affected parents and another affected child might demonstrate clinically silent T2-weighted lesions; and that monozygotic twins with MS are more likely to express similar T2-weighted lesion volumes than non-twin sibling pairs. We found clinically silent lesions in unaffected children of the symptomatic parent couple, with a significant difference in total T2 lesion volume between these unaffected siblings and their parents, as well as their affected brother. In our other sibling pairs, T2 lesion volumes were similar between the twins and significantly different in the non-twin pair, despite similar levels of clinical functioning as determined by EDSS scoring. These results suggest that foci of demyelination might be expected in clinically normal offspring of parents with MS, possibly reflecting a genetic predisposition to subsequent development of MS.     

Lesion distribution in children with clinically isolated syndromes

We evaluated the incidence, volume, and spatial distribution of T2-weighted magnetic resonance imaging lesions in 58 children with clinically isolated syndromes at risk for multiple sclerosis compared with 58 adults with relapsing-remitting multiple sclerosis. Pediatric patients with clinically isolated syndromes who had brain lesions had supratentorial lesion volumes similar to adult multiple sclerosis patients, but greater infratentorial lesion volumes (p < 0.009), particularly in the pons of male patients. The predilection for infratentorial lesions the pediatric patients with clinically isolated syndromes may reflect immunological differences or differences in myelin, possibly related to the caudorostral temporal gradient in myelin maturation.     

Wolfram syndrome: Hereditary diabetes mellitus with brainstem and optic atrophy

Wolfram syndrome was originally described as a combination of familial juvenile-onset diabetes mellitus and optic atrophy. Other neurological features subsequently emerged, and “DIDMOAD” (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness) became a commonly accepted acronym. Here, we describe 4 further cases from 2 families, in whom there occurred previously unrecognized neurological features, central apnea and neurogenic upper airway collapse, together precipitating primary respiratory failure (fatal in 1 case), startle myoclonus (in 2 unrelated cases), axial rigidity, and Parinaud's syndrome. Magnetic resonance images revealed striking brainstem atrophy affecting, in particular, the pons and midbrain. The mitochondrial DNA from 3 cases (and relatives) showed no evidence of any of the previously reported abnormalities. These neurological and neuroradiological features, in conjunction with (1) analyses showing the neurodegenerative origin of optic atrophy, deafness, diabetes insipidus, and incontinence, (2) other previously reported neurological complications (including anosmia, ataxia, epilepsy, and neuropsychiatric and cognitive abnormalities), and (3) the very small number of published postmortem studies, indicate that Wolfram syndrome should be reemphasized as a unique hereditary neurodegenerative disorder with prominent optic atrophy and diabetes mellitus.     

Lateral extradural,supratentorial neurenteric cyst

Neurenteric cysts are rare congenital, benign, endodermal lesions of the central nervous system that occur mainly in the spinal canal. Intracranial neurenteric cysts are rare; the posterior fossa being the most common site. A laterally based supratentorial neurenteric cyst is exceptionally uncommon. The rarity of supratentorial neurenteric cysts and their variable imaging features preclude preoperative diagnosis. A search of the literature revealed no other extradural supratentorial neurenteric cyst. We present a patient with an extradural giant neurenteric cyst that occupied both the supratentorial and infratentorial compartments, further highlighting the heterogeneity of this rare intracranial lesion and emphasizing the need to consider this in the differential diagnosis of cystic intracranial brain lesions.     

Multiple intracranial enterogenous cysts.

The case of a 40-year-old woman with increasing ataxia is described. Although the clinical presentation and evoked response studies raised the possibility of multiple sclerosis, further investigation revealed multiple cystic intracranial lesions. Surgical excision of one of the lesions relieved the patient's symptoms. Histological examination revealed that this was an enterogenous cyst. Although single cysts of this type have rarely been reported occurring in the posterior cranial fossa, the occurrence of multiple lesions, some in the supratentorial compartment, appears to be unique.     

Magnetic resonance imaging in intracranial paracoccidioidomycosis.

Paracoccidioidomycosis is a systemic mycosis, endemic in South and Central America, that affects the central nervous system (CNS) in almost 10% of patients. Neurological involvement includes two different clinical forms: meningeal and granulomatous, also known as the pseudotumor form. Five patients with biopsy-proved systemic paracoccidioidomycosis and neurological complaints were studied by magnetic resonance imaging. CNS involvement was detected in all patients in the form of multiple round or lobulated lesions, predominantly hypointense on T2-weighted images and ring or nodular enhancement on post-gadolinium T1-weighted images. The lesions were distributed diffusely, with a slight predominance in the supratentorial compartment, although infratentorial lesions were also observed, mainly in the cerebellum. Hypointense lesions on T2-weighted images persisted in all 3 patients reexamined after treatment, whereas enhancing lesions on post-gadolinium T1-weighted images turned isointense in 2 patients. Magnetic resonance imaging is a sensitive method in documenting CNS paracoccidioidomycosis, most frequently as supratentorial and infratentorial multiple, round or lobulated hypointense lesions on T2-weighted images.     

Supratentorial hemangioblastoma

Hemangioblastomas are extremely rare in supratentorial locations, and to date, approximately 128 cases of supratentorial hemangioblastoma have been reported in the literature. Here, we report a female case of supratentorial hemangioblastoma, not associated with von Hippel-Lindau disease. We describe its clinical, neuropathological, and neuroradiological characteristics, elaborate the surgical protocols, and follow-up methods, and review the pertinent literature.     

Exome capture sequencing identifies a novel CCM1 mutation in a Chinese family with multiple cerebral cavernous malformations

Purpose: Cerebral cavernous malformations (CCMs) are vascular anomalies predominantly in the central nervous system but may include lesions in other tissues, such as the retina, skin and liver. The main clinical manifestations include seizures, hemorrhage, recurrent headaches and focal neurological deficits. Previous studies of familial CCMs (FCCMs) have mainly reported in Hispanic and Caucasian cases. Here, we report on FCCMs in a Chinese family further characterized by a novel CCM1 gene mutation. Materials and methods: We investigated clinical and neuroradiological features of a Chinese family of 30 members. Furthermore, we used exome capture sequencing to identify the causing gene. The CCM1 mRNA expression level in three patients of the family and 10 wild-type healthy individuals were detected by real-time quantitative polymerase chain reaction (real-time RT-PCR). Results: Brain magnetic resonance imaging demonstrated multiple intracranial lesions in seven members. The clinical manifestation of CCM was found in five of these cases, including recurrent headaches, weakness, hemorrhage and seizures. Moreover, we identified a novel nonsense mutation c.1159G>T (p. E387*) in the CCM1 gene in the pedigree. Based on real-time RT-PCR results, we have found that the CCM1 mRNA expression level in three patients was reduced by 35% than that in wild-type healthy individuals. Conclusions: Our finding suggests that the novel nonsense mutation c.1159G>T in CCM1 gene is associated with FCCM, and that CCM1 haploinsufficiency may be the underlying mechanism of CCMs. Furthermore, it also demonstrates that exome capture sequencing is an efficient and direct diagnostic tool to identify causes of genetically heterogeneous diseases.