Urbach-Wiethe disease in a young patient without apparent amygdala calcification.

Urbach-Wiethe disease is an extremely rare genetically-based syndrome which usually leads to dermatological and neurological changes. Neurologically, the amygdaloid region is primarily bilaterally affected. Therefore, several functions modulated by the amygdala are changed in patients with Urbach-Wiethe disease. As the neurological alterations evolve only gradually, it is particularly important to determine the cognitive and brain status of a juvenile. The patient described here was seen briefly at age 9 and tested neuropsychologically at age 19; furthermore, computer tomography and magnetic resonance imaging of his head was done. There were no important abnormalities in the brain, which is unusual in the light of previous data from other patients. On the cognitive level, the patient was generally within normal limits. However, he had mild problems in attention and concentration, and more prominent problems in emotional processing domain, and in personality dimensions. It is concluded that amygdala calcifications in Urbach-Wiethe disease take place progressively-possibly underpinned by genetic and gender variables; this can subsequently allow psychosocial-social factors (such a proper education and socialization) and biological factors (compensatory neuroplasticity) to retard and diminish the development of socio-emotional and cognitive deteriorations, though the outcome of questionnaires indicates that such patients may develop substantial concerns as to their future life and well-being.

Are the kidneys involved in lipoid proteinosis? Study of 22 patients.

AIM: Lipoid proteinosis (LP) is a systemic, progressive, rare genodermatosis that manifests in early life with mucocutaneous lesions. Kidney involvement has not been described before, hence we aimed to investigate kidney findings in LP patients. MATERIALS AND METHODS: In this cross-sectional study, LP patients who were followed up and diagnosed with clinical, histopathological and radiological findings in the Dermatology outpatient clinic were invited to the Pediatric Nephrology Clinic. Biochemical, spot urine and 24-hour urine collection tests and ultrasound scans were scanned for the functional and anatomical status of the kidneys. Healthy controls who visited the Pediatric Nephrology Clinic during study periods for other reasons were invited to participate as the control group. RESULTS: Data of 44 participants (22 LP patients, mean age 14.5 years and 22 healthy controls, mean age 14.3 years) were available for the analysis. Ultrasound scans revealed simple renal cysts in 68% of LP patients. The cysts were bilateral in 4 patients, while no cyst was detected in healthy controls. Biochemical parameters, proteinuria, and albuminuria were all within the normal reference range in both LP patients and healthy controls, whereas LP patients had statistically significant lower serum albumin and higher C-reactive protein levels than healthy controls. CONCLUSION: Multiple simple renal cysts were detected in the majority of LP patients, and this finding could be part of the systemic involvement of the disease. Renal functions and biochemical parameters were within the normal reference range, but low serum albumin and high C-reactive protein levels in LP patients may be the signs of elevated systemic inflammation. Although more studies are needed to better define these findings, the presence of many simple renal cysts in LP patients was found to be the most important finding of this study.

A Protective Mechanism against Illusory Perceptions Is Amygdala-Dependent.

Most people have a clear sense of body ownership, preserving them from physical harm. However, perceptual body illusions - famously the rubber hand illusion (RHI) - can be elicited experimentally in healthy individuals. We hypothesize that the amygdala, a core component of neural circuits of threat processing, is involved in protective mechanisms against disturbed body perceptions. To test this hypothesis, we started by investigating two monozygotic human twin sisters with focal bilateral amygdala damage due to Urbach-Wiethe disease. Relative to 20 healthy women, the twins exhibited, on two occasions 1 year apart, augmented RHI responses in form of faster illusion onset and increased vividness ratings. Following up on these findings, we conducted a volumetric brain morphometry study involving an independent, gender-mixed sample of 57 healthy human volunteers (36 female, 21 male). Our results revealed a positive correlation between amygdala volume and RHI onset, i.e., the smaller the amygdala, the less time it took the RHI to emerge. This raised the question of whether a similar phenotype would result from experimental amygdala inhibition. To dampen amygdala reactivity, we intranasally administered the peptide hormone oxytocin to the same 57 individuals in a randomized trial before conducting the RHI. Compared with placebo, oxytocin treatment yielded enhanced RHI responses, again evident in accelerated illusion onset and increased vividness ratings. Together, the present series of experiments provides converging evidence for the amygdala's unprecedented role in reducing susceptibility to the RHI, thus protecting the organism from the potentially fatal threats of a distorted bodily self.SIGNIFICANCE STATEMENT Compelling evidence indicates that the amygdala is of vital importance for danger detection and fear processing. However, lethal threats can arise not only from menacing external stimuli but also from distortions in bodily self-perception. Intriguingly, the amygdala's modulatory role in such illusory body perceptions is still elusive. To probe the amygdala's involvement in illusory body experiences, we conducted a multi-methodological series of experiments in a rare human amygdala lesion model, complemented by a morphological and pharmaco-modulatory experiment in healthy volunteers. Our findings convergently suggest that the amygdala's integrity is indispensable for maintaining an unbiased, precise perception of our bodily self. Hence, the amygdala might shield us against distortions in self-perception and the resultant loss of behavioral control of our organism.

Lipoid proteinosis: A case with distinct histopathological and radiological findings.

Lipoid proteinosis is a rare inherited genodermatosis characterized by hyaline deposits in various tissues. Clinically, it manifests with cutaneous as well as extracutaneous features. Periodic acid-Schiff (PAS)-reactive hyaline deposits in the upper dermis, with localization around blood vessels and eccrine sweat glands, in particular, is the histopathological hallmark finding. On brain imaging, bilateral symmetrical temporal lobe calcifications are considered to be pathognomonic of this disorder. We report a case of lipoid proteinosis in which hyaline deposits were present in the papillary and reticular dermis, without being seen at the periphery of eccrine sweat glands, along with dystrophic calcification. Magnetic resonance imaging (MRI) of brain revealed hydrocephalus, subependymal heterotropia and absent splenium of corpus callosum with no evidence of temporal lobe calcification. Thus, our case highlights the inherent diverse nature of lipoid proteinosis.

The Basolateral Amygdalae and Frontotemporal Network Functions for Threat Perception.

Although the amygdalae play a central role in threat perception and reactions, the direct contributions of the amygdalae to specific aspects of threat perception, from ambiguity resolution to reflexive or deliberate action, remain ill understood in humans. Animal studies show that a detailed understanding requires a focus on the different subnuclei, which is not yet achieved in human research. Given the limits of human imaging methods, the crucial contribution needs to come from individuals with exclusive and selective amygdalae lesions. The current study investigated the role of the basolateral amygdalae and their connection with associated frontal and temporal networks in the automatic perception of threat. Functional activation and connectivity of five individuals with Urbach-Wiethe disease with focal basolateral amygdalae damage and 12 matched controls were measured with functional MRI while they attended to the facial expression of a threatening face-body compound stimuli. Basolateral amygdalae damage was associated with decreased activation in the temporal pole but increased activity in the ventral and dorsal medial prefrontal and medial orbitofrontal cortex. This dissociation between the prefrontal and temporal networks was also present in the connectivity maps. Our results contribute to a dynamic, multirole, subnuclei-based perspective on the involvement of the amygdalae in fear perception. Damage to the basolateral amygdalae decreases activity in the temporal network while increasing activity in the frontal network, thereby potentially triggering a switch from resolving ambiguity to dysfunctional threat signaling and regulation, resulting in hypersensitivity to threat.

Paradoxical facilitation of working memory after basolateral amygdala damage.

Working memory is a vital cognitive capacity without which meaningful thinking and logical reasoning would be impossible. Working memory is integrally dependent upon prefrontal cortex and it has been suggested that voluntary control of working memory, enabling sustained emotion inhibition, was the crucial step in the evolution of modern humans. Consistent with this, recent fMRI studies suggest that working memory performance depends upon the capacity of prefrontal cortex to suppress bottom-up amygdala signals during emotional arousal. However fMRI is not well-suited to definitively resolve questions of causality. Moreover, the amygdala is neither structurally or functionally homogenous and fMRI studies do not resolve which amygdala sub-regions interfere with working memory. Lesion studies on the other hand can contribute unique causal evidence on aspects of brain-behaviour phenomena fMRI cannot "see". To address these questions we investigated working memory performance in three adult female subjects with bilateral basolateral amygdala calcification consequent to Urbach-Wiethe Disease and ten healthy controls. Amygdala lesion extent and functionality was determined by structural and functional MRI methods. Working memory performance was assessed using the Wechsler Adult Intelligence Scale-III digit span forward task. State and trait anxiety measures to control for possible emotional differences between patient and control groups were administered. Structural MRI showed bilateral selective basolateral amygdala damage in the three Urbach-Wiethe Disease subjects and fMRI confirmed intact functionality in the remaining amygdala sub-regions. The three Urbach-Wiethe Disease subjects showed significant working memory facilitation relative to controls. Control measures showed no group anxiety differences. Results are provisionally interpreted in terms of a 'cooperation through competition' networks model that may account for the observed paradoxical functional facilitation effect.

Lipoid proteinosis of Urbach and Weithe: case report and a brief review of the literature.

Lipoid proteinosis is a rare disorder involving multiple organ systems. The ocular manifestations are usually trivial, but greatly aid in the diagnosis. We describe a patient who presented to us with typical moniliform blepharosis. A brief description of relevance to the ophthalmologist and review of the literature follows.

Lipid proteinosis: a case report.

Lipid proteinosis, also known as Urbach-Wiethe disease, is a rare autosomal recessive disorder. It presents in early childhood with hoarseness of voice, skin infiltration and thickening, beaded papules on the eyelid margin, and facial acneform scars. Oral findings such as woody tongue and papules on the oral mucosa are common findings. To the authors' knowledge, only about 250 cases have been reported to date. The occurrence of this disease in this part of the world is rare.

Reduced 5-HT(2A) receptor signaling following selective bilateral amygdala damage.

Neurobiological evidence implicates the amygdala as well as serotonergic (serotonin, 5-HT) signaling via postsynaptic 5-HT(2A) receptors as essential substrates of anxiety behaviors. Assuming a functional interdependence of these substrates, we hypothesized that a low-fear behavioral phenotype due to bilateral lesion of the amygdala would be associated with significant 5-HT(2A) receptor changes. Thus, we used [(18)F]altanserin positron emission tomography (PET) referenced to radioligand plasma levels and corrected for partial volume effects to quantify the spatial distribution of 5-HT(2A) receptor binding potential (BP(P)) in a rare patient with Urbach-Wiethe disease and selective bilateral amygdala calcification damage relative to 10 healthy control subjects. Consistent with our a priori hypothesis, we observed a 70% global decrease in 5-HT(2A) receptor BP(P) in the Urbach-Wiethe patient relative to controls. Thus, brain abnormalities in this patient are not restricted to the amygdala, but extend to overall 5-HT neurotransmission via 5-HT(2A) receptors. Our findings provide important insights into the molecular architecture of human anxiety behaviors and suggest the 5-HT(2A) receptor as a promising pharmacological target to control pathological anxiety.

Epilepsy and migraine in a patient with Urbach-Wiethe disease.

We report the clinical, neuroradiological, and molecular genetic findings in a patient with lipoid proteinosis or Urbach-Wiethe disease. Interestingly, in this patient epilepsy and migraine were the symptoms leading to the diagnosis of the disease, contrary to most patients in whom skin abnormalities are the first recognized symptoms.

Amygdalae calcifications associated with disease duration in lipoid proteinosis.

OBJECTIVES: To describe imaging findings of central nervous system involvement in patients with lipoid proteinosis. METHODS: Patients with lipoid proteinosis followed in the dermatology and neurology departments of the State University of Campinas between 2002 and 2004 were evaluated using high-resolution MRI and computerized tomography (CT). RESULTS: We reviewed the charts of three patients (two women) with lipoid proteinosis with, ages ranging from 5 to 44 years. Symptomatic disease duration ranged from 2 to 39 years. MRI scans showed hypointense signal in FLAIR and T2 images in the amygdalae in two of three patients. Brain CT scans from two patients showed that MRI findings were calcifications. The calcification was more evident in patients with longer disease duration. Epilepsy was identified in one patient with longer disease duration. No other epileptogenic lesion was identified on MRI in this patient. CONCLUSION: Lipoid proteinosis is associated with bilateral amygdalae calcification. These findings were more evident in patients with longer disease duration. Epilepsy, when present, may be related to these calcifications. Patients with lipoid proteinosis should be followed with MRI/CT in order to identify these abnormalities.

Amygdala, affect and cognition: evidence from 10 patients with Urbach-Wiethe disease.

Patients with Urbach-Wiethe disease constitute a unique nature experiment as more than half have bilaterally symmetrical damage in the amygdaloid region. Ten such patients were studied neuropsychologically and, nine of them, neuroradiologically with static (CT) and functional imaging techniques [single-photon emission computed tomography (SPECT) and PET]. Their principal bilateral amygdala damage was confirmed. Neuropsychologically, the patients showed cognitively little deviation from normal subjects, while they differed emotionally. This was evident in their judgement of all emotions in facial expressions, in an odour-figure association test as well as in remembering negative and positive pictures. This suggests that the human amygdala influences both negative and positive emotional processing.

[Urbach-Wiethe disease/lipoidproteinosis]. / Doença de Urbach-Wiethe/proteinose lipoidica.

The authors present a case of Urbach-Wiethe's disease (lipoid proteinosis), a rare autosomal recessive disorder, in a 49-year-old female patient with pathognomonic cranial radiological findings demonstrated by radiology and computed tomography. The rarity of this pathology made radiological diagnosis difficult.

Case report: computed tomography findings in lipoid proteinosis: report of two cases.

Lipoid proteinosis (Urbach-Wiethe disease (Urbach, E and Wiethe, C, Lipoidosis cutis mucosae, Virchows Arch. Patholog. Anat., 273, 285-319 (1929)) is a rare generalized disease with autosomal recessive inheritance. It most often involves the skin and mucosal membranes of the aerodigestive tract; but also involves the central nervous system, lung, lymph nodes and striated muscles. We present the computed tomography findings in the cranium and larynx of two siblings with lipoid proteinosis.

[Cutaneous-mucosal hyalinosis with cerebral sites. 3 new cases]. / Hyalinose cutanéo-muqueuse avec localisations cérébrales. Trois nouveaux cas.

The authors report about 3 new cases of cutaneous-mucosal hyalinosis, or Urbach-Wiethe disease, with cerebral sites. The intracranial calcifications were detected without any neurological presenting features, and were discovered incidentally on radiographs of the skull. The CT examination allows specifying the site of these calcifications, in the gyri of the hippocampus.

Radiological findings in lipoid proteinosis.

The radiological findings in six patients suffering from lipoid proteinosis have been described and discussed. Laryngeal examination showed thickened epiglottis, swollen arytenoids and aryepiglottic folds, thickened irregular false and true vocal cords, and increased stiffness of the vocal cords. The ventricles and subglottic region were free. Bean-shaped suprasellar calcifications were found in two cases who were free of neurological symptoms. The chest and upper gastro-intestinal tract were radiologically free.

Radiographic and computed tomographic findings in lipid proteinosis. A case report.

A case of lipoid proteinosis in an 18-year-old youth is presented. The typical clinical findings in patients with this rare disorder are discussed. Emphasis is placed on the radiographic and computed tomographic appearances. The bean-shaped calcific densities, which are located in the region of the hippocampi in this case, are illustrated.