Brainstem calcification in Möbius syndrome

M?bius syndrome is characterized by congenital facial diplegia, and may be associated with limb or orofacial malformations. A number of mechanisms have been proposed to explain the pathogenesis, including prenatal ischemia. We identified seven children with M?bius syndrome over the 10-year interval 1992-2001, all of whom manifested incomplete bilateral facial palsy. Associated limb and orofacial anomalies were observed in six cases. Computed tomographic scans were available in six children, and five of them manifested brainstem calcification which was most prominent in the floor of the fourth ventricle. The calcification was detected as early as 7 days of age and did not change with time, suggesting a static condition of prenatal onset. These observations support the hypothesis that the pathology in M?bius syndrome is secondary to prenatal brain ischemia.     

Intracranial calcification, retinopathy, and osteopenia: a new syndrome?

We describe two brothers with bilateral exudative retinopathy, intracranial calcifications, a sclerotic bony disorder, and normal intelligence. The younger brother also has osteopenia, mild splenomegaly, and pancytopenia. We review the literature with emphasis on the unique features of these patients.     

Intracranial white epidermoid cyst with dystrophic calcification – A case report and literature review

White epidermoids are a rare variant of an intracranial epidermoid cyst that do not exhibit typical ‘near- cerebrospinal fluid (CSF)’ CT density or MRI intensity. Here, the authors present the case of a 58 year old man with an acute onset of aphasia and altered consciousness, due to a large heterogeneous cranial mass in the left frontal region with unusual signal intensity. Subsequent histopathological analysis identified the lesion as an epidermoid cyst.     

NACP/α-synuclein immunoreactivity in diffuse neurofibrillary tangles with calcification (DNTC)

Diffuse neurofibrillary tangles with calcification (DNTC) is a rare tangle-predominant dementia, as well as one of the tauopathies lacking Abeta deposition. It is characterized by temporo-frontal lobar atrophy, Fahr-type calcification and, histopathologically, numerous neurofibrillary tangles in the limbic system and neocortex. Recently, accumulation of alpha-synuclein (alphaS), the precursor of the non-beta amyloid component (NAC) of Alzheimer's disease, has been shown in diverse neurodegenerative disorders, including Parkinson's disease, dementia with Lewy bodies, Alzheimer's disease, multiple system atrophy and parkinsonism-dementia complex of Guam. To clarify whether alphaS accumulates in other neurodegenerative disorders, we investigated eight DNTC brains using immunohistochemistry and demonstrated remarkable alphaS deposition in the neurons and astrocytes in many anatomical regions. Abundant Lewy bodies were observed in the amygdala (seven cases) and hippocampus (seven cases), and, to a lesser degree, in the substantia nigra (six cases) and dorsal vagal nucleus (five cases). In the hippocampus, many Lewy neurites were distributed in the stratum oriens and stratum pyramidale in the CA2-3 and the subiculum. Furthermore, numerous NAC-positive astrocytes were detected in the hippocampus and temporal cortex. This investigation reveals that neurons and astrocytes are extensively involved in remarkable alphaS pathology in the DNTC brain, and that the alphaS pathology compounds the cardinal pathological features of tau pathology. These findings suggest that (1) DNTC shares a common pathophysiological background with Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy in which abnormal alphaS aggregation is observed, and (2) there is an interaction between alphaS and tau pathology that does not involve amyloid in DNTC.     

Argyrophilic grains are not always argyrophilic—Distinction from neurofibrillary tangles of diffuse neurofibrillary tangles with calcification revealed by comparison between Gallyas and Campbell-Switzer methods

Silver staining profiles of argyrophilic grains (AGs) and of neurofibrillary tangles (NFTs) of diffuse neurofibrillary tangles with calcification (DNTC, collectively as DNTC-NFTs) were examined for their relation to tau- and ubiquitin-like immunoreactivity (IR). Pairs of mirror sections were triple-fluorolabeled with an anti-PHF tau (AT8) antibody, an anti-ubiquitin antibody and thiazin red (TR), a fluorochrome that identifies fibrillary structures such as NFTs of Alzheimers disease (AD). One of the paired sections was subsequently stained with Gallyas method (GAL), and the other with Campbell-Switzer method (CS). Comparison of the same microscopic field on the paired fluorolabeled sections, subsequently silver-stained with either GAL or CS enabled the determination of five different profiles of each structure: AT8-IR, ubiquitin-like-IR, affinity to TR, argyrophilia with GAL or CS staining. AGs, mainly composed of four-repeat (4R) tau, were argyrophilic with GAL but not with CS, and their affinity to TR and ubiquitin-like-IR was not intense. This staining profile of AGs is identical with those of tau-positive structures in the cortex of progressive supranuclear palsy/corticobasal degeneration, both composed of 4R tau. This selective affinity of AGs to GAL is in sharp contrast with Pick bodies, composed of three-repeat (3R) tau, that are positive for CS but not for GAL, as we reported previously. This contrast is explainable if the argyrophilia with CS is related to deposits containing 3R tau, while that with GAL is linked to those containing 4R tau. Indeed, DNTC-NFTs, that contain both 3R and 4R tau, were argyrophilic with CS and GAL, and their affinity to TR and ubiquitin-like-IR were consistent, as we reported previously for NFTs of AD and of Downs syndrome, both similarly composed of 3R and 4R tau. Taken together, differences in molecular composition of tau protein in these deposits are linked to their argyrophilic properties dependent on the staining method in these sporadic tauopathies. Although explanations for these empirical differences are not yet available, awareness of this clear distinction is potentially of diagnostic and pathological significance.     

Mental retardation,spasticity, basal ganglia calcification,cerebral white matter lesions,multiple endocrine defects,telangiectasia and atrophic skin: A new syndrome?

We report on an 8-year-old boy with mental retardation and spastic tetraparesis associated with atrophic skin on the face and extremities, telangiectasia, and severe dental caries. Basal ganglia calcification and multiple lesions in the subcortical white matter have been present since infancy. The patient has complications of liver dysfunction, multiple endocrine defects, and elevation of blood/cerebrospinal fluid lactate. Extensive laboratory examinations, including skin and muscle biopsies, and UV- and mitomycin C-sensitivity tests on fibroblasts, provided no evidence of a specific disease entity. No deterioration was noted, and supplementation of riboflavin and other vitamins had no apparent effect on the neurodevelopmental status of this patient. This patient may represent a novel disease entity, with unclear pathogenesis.