[To finish with fear of dental care]. / Pour en finir avec la peur des soins dentaires.

The patient facing the dentist knows fear, anxiety. The symbolism of the mouth and teeth from childhood is an entirely specific nature of the human body. The terrifying image of dental treatment and dentist that has long been stigmatized through painting, literature, theater and cinema can change today. Many therapeutic options to the management of anxiety in dental phobia; anesthesia, conscious sedation, combined with a soothing cabinet, a caring dentist, targeted use of medications or milder alternative methods; homeopathy, herbal medicine, acupuncture, psychotherapy, places the patient's interests at the center of the caregiving relationship. But this treatment panel is also offered him the difficulty of the choice. This exercise without systematization, according to the patient with competence and kindness. Some patients may be sent or processed in collaboration with other health professionals.

Involvement of the cholinergic basal forebrain nuclei in spinocerebellar ataxia type 2 (SCA2).

AIMS: Spinocerebellar ataxia type 2 (SCA2) belongs to the CAG repeat or polyglutamine diseases. Along with a large variety of motor, behavioural and neuropsychological symptoms the clinical picture of patients suffering from this autosomal dominantly inherited ataxia may also include deficits of attention, impairments of memory, as well as frontal-executive and visuospatial dysfunctions. As the possible morphological correlates of these cognitive SCA2 deficits are unclear we examined the cholinergic basal forebrain nuclei, which are believed to be crucial for several aspects of normal cognition and may contribute to impairments of cognitive functions under pathological conditions. METHODS: We studied pigment-Nissl-stained thick tissue sections through the cholinergic basal forebrain nuclei (that is, medial septal nucleus, nuclei of the diagonal band of Broca, basal nucleus of Meynert) of four clinically diagnosed and genetically confirmed SCA2 patients and of 13 control individuals according to the pathoanatomical approach. The pathoanatomical results were confirmed by additional quantitative investigations of these nuclei in the SCA2 patients and four age- and gender-matched controls. RESULTS: Our study revealed a severe and consistent neuronal loss in all of the cholinergic basal forebrain nuclei (medial septal nucleus: 72%; vertical nucleus of the diagonal band of Broca: 74%; horizontal limb of the diagonal band of Broca: 72%; basal nucleus of Meynert: 86%) of the SCA2 patients studied. Damage to the basal forebrain nuclei was associated with everyday relevant cognitive deficits only in our SCA2 patient with an additional Braak and Braak stage V Alzheimer's disease (AD)-related tau pathology. CONCLUSIONS: The findings of the present study: (1) indicate that the mutation and pathological process underlying SCA2 play a causative role for this severe degeneration of the cholinergic basal forebrain nuclei and (2) may suggest that degeneration of the cholinergic basal forebrain nuclei per se is not sufficient to cause profound and global dementia detrimental to everyday practice and activities of daily living.

Spinocerebellar ataxia type 1 (SCA1): new pathoanatomical and clinico-pathological insights.

AIMS: Spinocerebellar ataxia type 1 (SCA1) represents the first molecular genetically characterized autosomal dominantly inherited cerebellar ataxia and is assigned to the CAG-repeat or polyglutamine diseases. Owing to limited knowledge about SCA1 neuropathology, appropriate pathoanatomical correlates of a large variety of SCA1 disease symptoms are missing and the neuropathological basis for further morphological and experimental SCA1 studies is still fragmentary. METHODS: In the present study, we investigated for the first time serial tissue sections through the complete brains of clinically diagnosed and genetically confirmed SCA1 patients. RESULTS: Brain damage in the three SCA1 patients studied went beyond the well-known brain predilection sites of the underlying pathological process. Along with neuronal loss in the primary motor cortex, it included widespread degeneration of gray components of the basal forebrain, thalamus, brainstem and cerebellum, as well as of white matter components in the cerebellum and brainstem. It involved the motor cerebellothalamocortical and basal ganglia-thalamocortical circuits, the visual, auditory, somatosensory, oculomotor, vestibular, ingestion-related, precerebellar, basal forebrain cholinergic and midbrain dopaminergic systems. CONCLUSIONS: These findings show for the first time that the extent and severity of brain damage in SCA1 is very similar to that of clinically closely related spinocerebellar ataxias (that is, SCA2, SCA3 and SCA7). They offer suitable explanations for poorly understood SCA1 disease symptoms and will facilitate the interpretation of further morphological and experimental SCA1 studies.

Amyloid deposits in senile vertebral arteries, immunohistological and ultrastructural findings.

In a study on amyloid deposits in vertebral arteries, many elderly patients showed amyloid deposits in the perivascular tissue. These proved to be senile systemic amyloidosis of the transthyretin-type by immunohistochemistry. Amyloid deposits were also found in the arterial wall. These intramural amyloid deposits showed significant affinity to elastic material of the arterial wall. The intramural amyloid deposits did not react with any of the known or available antibodies to amyloid subtypes. Only a polyclonal antibody to human elastin could mark this type of amyloid. It may therefore be assumed that the precursor protein of this amyloid is derived from elastin molecules. By electron microscopy, the light microscopic amyloid deposits were of fibrillary structure, typical for amyloid with a direct contact to elastic material.

[Childhood achalasia: a separate entity?]. / Achalasie im Kindesalter: Eine separate Entität?

BACKGROUND: Achalasia in childhood is rare, also the etiology and the pathogenesis of the early onset ort he disease is practically unknown. Little is known about the neuropathological changes in structure of the esophageal wall in non-hereditary, sporadic achalasia in children and ist differentiation to that in adults. The aim of our study was to examine the morphological properties or high-pressure zone of the lower esophageal sphincter in children who had undergone a Heller myotomy because of achalasia as well as to compare them with the pathological findings in adults. METHODS: Muscle biopsies of the smooth musculature, a 20 x 10 mm long segment of the myenteric of the distal esophagus (lower boundary of the esophageal incision of the myotomy), were taken for histopathological and immunohistochemical studies. RESULTS: A conspicuous histomorphological finding was a marked reduction of the myenteric ganglion through to complete aganglionosis of the high-pressure zone of the lower esophageal sphincter. In contrast to achalasia in adults, neural inflammation was found only rarely. A pronounced fibrosis of the smooth muscle layers was found in all patients whereas muscular hypertrophy or visceral myopathy was not present. The interstitial Cajal cells were reduced, similar to those in adults. CONCLUSIONS: The variability of the clinical and pathological properties in cases of childhood achalasia are indicative of a complex pattern of varying etiologies and a comparison with the disease in adults does not, in principle, allow the assumption of a separate clinical entity. The present findings are compatible with the histopathological results of hereditary achalasia in children as described for Allgrove's syndrome.

A new type of leukoencephalopathy with metaphyseal chondrodysplasia maps to Xq25-q27.

BACKGROUND: The authors report a three-generation family with four male patients presenting with a novel type of X-chromosomal leukoencephalopathy associated with skeletal abnormalities. METHODS: The index patient and his brother reached their early motor milestones in due time and had normal language development. Between the ages of 2 and 3 years, first signs of spastic paraplegia were noticed. Furthermore, the patients developed tremor, ataxia, optic atrophy, and spastic tetraparesis. Both boys had broad wrists and knees without significant contractures. A maternal uncle and a granduncle had the same disease. RESULTS: Leukoencephalopathy (MRI, MRS) and metaphyseal chondrodysplasia (X-ray, MRI) were diagnosed. MRS showed a reduction of choline-containing compounds in the white matter. An autopsy on one of the patients, who died at age 37 years, revealed an orthochromatic type of leukoencephalopathy. In bone and cartilage tissue, unspecific signs of a mild chondrodysplasia were found. At the PLP gene locus an obligate recombination was observed, which excludes the Pelizaeus-Merzbacher locus on Xq21-22. However, affected males share a fragment of the long arm of chromosome X. CONCLUSION: The authors report a new type of leukoencephalopathy associated with metaphyseal chondrodysplasia located on Xq25-q27.

[Esophageal resection for non-specific esophageal motility disorder]. / Osophagusresektion bei unspezifischer Motilitätsstörung der Speiseröhre -- Bedeutung der neuropathologischen Befunde.

A 47-year-old patient presented with a history of dysphagia for solid food for almost 10 years and weight loss of more than 50 kg. Non-resecting surgical as well as endoscopic procedures (laparoscopic cardiomyotomy with secondary antireflux operations, balloon dilation, Botulinum-toxin injection) were without success. A barium esophagogram showed a confinement of the distal esophagus with a filiform passage of the contrast medium and undigested food in the prestenotic dilated esophageal corpus. Manometry displayed a hypertensive lower esophageal sphincter with a resting pressure of 43.8 mmHg - although completely relaxing. The tubular esophagus was aperistaltic with 100 % simultaneous and repetitive contractions. As all attempts of previous therapy had failed, a transhiatal esophagectomy with gastric pull-up and cervical esophagogastrostomy ensued. Neuropathological examination of the esophagus showed that degeneration of the myenteric plexus was not severely involved, whereas inflammatory and fibrotic changes were obvious. Esophageal resection provided the only chance of a long-term benefit for our patient with relief of dysphagia.

Extended pathoanatomical studies point to a consistent affection of the thalamus in spinocerebellar ataxia type 2.

The involvement of the thalamus during the course of the currently known polyglutamine diseases is still a matter of debate. While it is well-known that this diencephalic nuclear complex undergoes neurodegeneration in some polyglutamine diseases such as Huntington's disease (HD), it has remained unclear whether and to what extent the thalamus is also involved in spinocerebellar ataxia type 2 (SCA2) patients. Encouraged by our recent post-mortem findings in one German SCA2 patient and the results of a recent nuclear magnetic resonance (NMR) study, we extended our pathoanatomical analysis to serial thick sections stained for lipofuscin granules and Nissl substance through the thalami of four additional German and Cuban SCA2 patients. According to this analysis the thalamus is consistently affected by the destructive process of SCA2. In particular, during our study we observed a consistent involvement of the lateral geniculate body, the lateral posterior, ventral anterior, ventral lateral, ventral posterior lateral, and ventral posterior medial thalamic nuclei as well as the extraterritorial reticular nucleus. In four of the SCA2 cases studied additional damage was seen in the inferior and lateral nuclei of the pulvinar, whereas in the minority of the patients a subset of the limbic nuclei of the thalamus (i.e. anterodorsal, anteroprincipal, laterodorsal, fasciculosus, mediodorsal, central lateral, central medial, cucullar, and paracentral nuclei, medial nucleus of the pulvinar) underwent neurodegeneration. These interindividual differences in the distribution pattern of thalamic neurodegeneration indicate that the thalamic nuclei differ in their proclivities to degenerate in SCA2 and may suggest that they become involved at different phases in the evolution of the underlying degenerative process.

Spinocerebellar ataxias types 2 and 3: degeneration of the pre-cerebellar nuclei isolates the three phylogenetically defined regions of the cerebellum.

The pre-cerebellar nuclei act as a gate for the entire neocortical, brainstem and spinal cord afferent input destined for the cerebellum. Since no pathoanatomical studies of these nuclei had yet been performed in spinocerebellar ataxia type 2 (SCA2) or type 3 (SCA3), we carried out a detailed postmortem study of the pre-cerebellar nuclei in six SCA2 and seven SCA3 patients in order to further characterize the extent of brainstem degeneration in these ataxic disorders. By means of unconventionally thick serial sections through the brainstem stained for lipofuscin pigment and Nissl material, we could show that all of the pre-cerebellar nuclei (red, pontine, arcuate, prepositus hypoglossal, superior vestibular, lateral vestibular, medial vestibular, interstitial vestibular, spinal vestibular, vermiform, lateral reticular, external cuneate, subventricular, paramedian reticular, intercalate, interfascicular hypoglossal, and conterminal nuclei, pontobulbar body, reticulotegmental nucleus of the pons, inferior olive, and nucleus of Roller) are among the targets of both of the degenerative processes underlying SCA2 and SCA3. These novel findings are in contrast to the current neuropathological literature, which assumes that only a subset of pre-cerebellar nuclei in SCA2 and SCA3 may undergo neurodegeneration. Widespread damage to the pre-cerebellar nuclei separates all three phylogenetically and functionally defined regions of the cerebellum, impairs their physiological functions and thus explains the occurrence of gait, stance, limb and truncal ataxia, dysarthria, truncal and postural instability with disequilibrium, impairments of the vestibulo-ocular reaction and optokinetic nystagmus, slowed and saccadic smooth pursuits, dysmetrical horizontal saccades, and gaze-evoked nystagmus during SCA2 and SCA3.

Contribution of diffusion tensor imaging to delineation of gliomas and glioblastomas.

PURPOSE: To determine if the diffusion tensor imaging (DTI) parameters fractional anisotropy (FA) and mean diffusivity (MD) can differentiate between accompanying edema and tumor cell infiltration of white matter (WM) beyond the tumor edge as defined from conventional MRI in low- and high-grade gliomas. MATERIALS AND METHODS: We examined 12 patients with high-grade gliomas/glioblastomas and eight patients with low-grade gliomas and compared them to 10 patients with meningiomas, in which no tumor infiltration is expected. The tumor was defined as the enhancing area in glioblastomas and meningiomas and as the area of increased T2-signal in low-grade gliomas. FA and MD were measured in the center of the tumor and in the adjacent WM. The contralateral WM and internal capsule were used as an internal standard. RESULTS: Comparing the WM areas of increased T2-signal adjacent to meningiomas and glioblastomas, we saw a trend (without significance) towards a reduction of FA, but not of MD, in glioblastomas. We found no changes of FA and MD in the WM adjacent to low-grade gliomas (without T2-signal increase) compared to the WM of the contralateral hemisphere. In meningiomas and high-grade gliomas/glioblastomas, a narrow rim of significantly (P < 0.01) increased FA and decreased MD values around the enhancing tumor area was seen, whereas in low-grade gliomas, such a rim could not be defined. There was no contribution of FA or MD to grading of gliomas. CONCLUSION: In glioblastomas, a reduction of FA in the edematous area surrounding the tumor may indicate tumor cell infiltration, but a reliable differentiation between infiltration and vasogenic edema is not yet possible on the basis of DTI. The additional finding of a narrow rim of increased FA and decreased MD at the edge of glioblastomas (as well as in meningiomas) may be caused by com-pressed WM fibers and/or increased vascularity, but does not contribute to exclude peripheral cellular infiltration.

Flow-cytometric DNA analysis of intracranial tumors in children.

The objective of this study was to investigate flow-cytometric DNA values of pediatric intracranial tumors, and to establish DNA analysis as a potential prognostic parameter. Twenty-nine brain tumor specimens from 26 pediatric patients were cryo-preserved within a 3-year period. The DNA content was measured by flow cytometry. Six of the tumor specimens had aneuploid DNA patterns. The median of the proliferation index was lower in the survivor group compared with the non-survivor group (36.4% and 47.5%, respectively). Ten of the 26 patients are still alive, eight were lost to follow up, and eight died. Flow-cytometric DNA analysis may be a helpful tool for examining brain tumors in children. The small size of this study could not establish flow cytometry as a definite prognostic factor, but further prospective multicenter studies will evaluate the prognostic significance of flow-cytometric DNA analysis.

Colocalization of different types of amyloid in the walls of cerebral blood vessels of patients suffering from cerebral amyloid angiopathy and spontaneous intracranial hemorrhage: a report of 5 cases.

Four cases of spontaneous intracranial hemorrhage (ICH) are described in which the diagnosis of a cerebral amyloid angiopathy (CAA) was made in the biopsy specimens. In one further case CAA was detected on autopsy after intracranial hemorrhage (ICH). Amyloidotic degeneration of the vessel walls appeared to be the most likely reason for the ICH which in these cases especially involved superficial neocortical regions. In all cases, co-deposition of A4beta-amyloid and ALlambda-amyloid was found in diseased leptomeningeal and cortical vessels. Besides CAA, all 5 patients suffered from other diseases which had affected the blood vessel walls such as atherosclerosis, diabetes mellitus or arterial hypertension. However, no signs of systemic amyloidosis could be detected in these cases. It is suggested that the observed co-deposition of 2 amyloid subtypes is based on the combination of 2 different diseases, one of which results in a local production of A4beta-amyloid in the tunica media of cerebral blood vessels and another one, e.g. arterial hypertension, which impairs the permeability of the blood vessels by affection of the tunica intima allowing for the pathological penetration of circulating immunoglobulin lambda-light chains into the vessel wall. Subsequently, the preexisting A4beta-amyloid might have induced the polymerization of the lambda-light chains to ALlambda-amyloid in the media of the vessels and could have aggravated the amyloidotic degeneration of the vessel walls.

[Bilateral progressive hearing loss as the first manifestation of metastatic carcinoma of the head of the pancreas. Case report]. / Beidseitige progrediente Hörminderung als Erstmanifestation eines metastasierenden Pankreaskopfkarzinoms. Kasuistik.

We report the history of a patient who presented first with a progressive unilateral hearing loss and later with a bilateral deafness and an unilateral facial nerve palsy as first and only symptoms of a pancreatic adenocarcinoma. By means of magnetic resonance tomography tumor-suspect lesions in both internal auditory canals were detected. Referring to the results of further examinations these intracanalicular lesions are most probably due to rarely seen bilateral metastasis of a pancreatic adenocarcinoma in the temporal bone. In addition to this rarely diagnosed localisation of metastasis it is rather uncommon that this kind of primary malignoma had not been detected because of gastrointestinal symptoms or extracranial metastasis.

Organisation and maturation of the human thalamus as revealed by CD15.

The distribution of the CD15 antigen (CD15, 3-fucosyl-N-acetyl-lactosamine, Lewis x) has been studied immunohistochemically in the fetal human thalamus. Its changing patterns could be related to three successive, but overlapping, periods primarily due to its association with radial glial cells, neuropil, and neural cell bodies, respectively. From 9 weeks of gestation (wg), a subset of CD15-positive radial glial cells distinguished the neuroepithelium of the ventral thalamus, a characteristic also seen in the developing mouse. Distal processes of the radial glial cells converged at the root of the forebrain choroid tenia, which was also CD15 positive. From 13 wg until approximately 20 wg, CD15-positive neuropil labeling marked the differentiation areas of prospective nuclei within the dorsal thalamus and progressively outlined their territories in a time sequence, which appeared specific for each nucleus. CD15 labeling of differentiating nuclei of the ventral, medial, anterior, and intralaminar thalamic divisions showed a transient topographic relationship with restricted areas of the ventricular wall. After 26 wg, CD15 immunoreactivity was observed in subpopulations of glial cells and neurons. Transient CD15 immunoreactivity was also found in delimited compartments within the subventricular region. The time of CD15 expression, its location, and cellular association suggest that CD15 is involved in segmentation of diencephalon, in the specification of differentiating nuclear areas and initial processes regarding the formation of intercellular contacts and cellular maturation.

Neurodegenerative diseases.

This article briefly discusses and illustrates the major important neurodegenerative diseases of adulthood and neurometabolic (neurodegenerative in a broader sense) diseases of childhood and their gross neuropathology. Macroscopic views of the brain including the cerebellum and the brain stem and the spinal cord are given by external inspection as well as gross sections after brain cutting. Histologic details and photographs are supplied to explain and corroborate certain gross findings. This article attempts to correlate nosologic and neuropathologic features as the basis for interpreting neuroimaging data.

[Fatal outcome during physiotherapy (Vojta's method) in a 3-month old infant. Case report and comments on manual therapy in children]. / Uber einen Todesfall während der Physiotherapie nach Vojta bei einem 3 Monate alten Säugling. Fallbeschreibung und Bemerkungen zur Manualtherapie bei Kindern.

Detailed clinical and neuropathological report on a fatal incident during the first manual therapy according to Vojta conducted in a 3 months old baby: during forced active rotation and head retraction the baby suffered from a bleeding into the adventitia of both her vertebral arteries at the level of C1 prompting ischemia of the caudal brainstem with subarachnoid haemorrhage around. It has to be suggested that similar cases already have occurred but have not been reported yet. There might be a time lag between the performance of physiotherapy and the beginning of neurologic symptoms. The risks of manual therapy in children will be discussed.

Immunohistochemical investigation of the brain of aged dogs. I. Detection of neurofibrillary tangles and of 4-hydroxynonenal protein, an oxidative damage product, in senile plaques.

In the aging dog brain lesions develop spontaneously. They share some morphological characteristics with those of Alzheimer 's disease in man. Diffuse and primitive plaques are well known, whereas neuritic plaques rarely develop. Neurofibrillary tangles have not been seen in the canine. The aim of the present investigation was to study major age-related changes of the dog's brain using paraffin sections with respect to cross-immunoreactivity of tau, A beta protein and other immunoreactive components including hydroxynonenal protein, which is a marker for oxidative damage. The occurrence of neurofibrillary tangles and of the protein tau therein was studied in serial brain sections of two dogs with the Gallyas stain and by immunohistochemistry with three different antibodies against tau. Senile plaques were stained with a monoclonal anti-A beta (residues 8-17), polyclonal anti-apolipoprotein E and a monoclonal antibody against 4-hydroxynonenal (HNE). Amyloid deposits and controls were screened by Congo red staining viewed in fluorescent light, followed by polarized light for green birefringence. With the Gallyas stain and one of the antisera against tau, neurofibrillary tangles were revealed in a similar dispersed pattern, whereas the other antitau antisera gave negative results. With the anti-HNE a positive reaction was found in cerebral amyloid deposits and in vascular wall areas where amyloid deposition was confirmed by Congo-red staining, and in perivascular cells and in some neurons. These results indicate that the canine with his tangles and plaques which show oxidative changes, forms a spontaneous modelfor understanding the early changes and their interrelationships in Alzheimer's disease.

Development-related expression of AKAP79 in the striatal compartments of the human brain.

The expression of AKAP79 which tethers regulatory proteins within postsynaptic densities has been studied in the two striatal compartments, i.e. patches and matrix, at different stages of the developing human brain by means of immunohistochemistry. The two striatal compartments exhibit various intensities of diffuse immunolabelling and a different number of immunoreactive nerve cells. From the 14th to 20th gestational week a nearly homogeneous distribution of immunoreactive structures in the two compartments of the striatum is seen. Thereafter, a decrease in immunoreactive structures within the matrix is observed (22nd-25th week, intermediate stage). From the 27th week onwards the patch compartment contains distinctly more immunoreactive puncta and nerve cells. Thus, the patches stand out clearly in the immunopreparations. This distribution pattern does not change during proceeding development. AKAP79-immunoreactive nerve cells closely resemble those constituting the class of medium-sized inhibitory projection neurons that receive the dopaminergic input of the striatum. Literature data suggest that AKAP79 may be functionally attributed to dopaminergic inputs. Accordingly, the patterns of AKAP79 expression can at least in part be correlated with the sequential occurrence of dopaminergic innervation. The mature matrix containing a dopaminergic innervation being as dense as in the patches displays distinctly less AKAP79-immunoreactive neurons and puncta than the patches. This discrepancy might indicate that a subpopulation of matrix neurons may, despite dopaminergic input, not express AKAP79.

Effect of fetal hydrocephalus on the distribution patterns of calcium-binding proteins in the human occipital cortex.

Neuronal pathology in the cerebral cortex (CC) of fetal hydrocephalus brains is quite subtle when applying routine Nissl staining. This study is aimed at investigating alterations of interneurons which can be immunolabelled by antibodies against the calcium-binding proteins calretinin (CR), calbindin (CB) and parvalbumin (PV). The subplate (SP) subjacent to the cortex anlage is included as this transient zone plays a pivotal role in the establishment of cortical connections. Nine occipital lobes from cases of fetal hydrocephalus and 9 controls were categorized according to age: 21-25 weeks of gestation (group 1) and 32-36 weeks (group 2). No differences in the distribution, number and morphology of CR-immunoreactive (ir) neurons are seen when comparing hydrocephalic with control brains of group 1. In severely altered hydrocephalic brains of group 2, the distribution and number of CR-, PV- and CB-ir nerve cells are not altered; however, they appear shrunken and processes are less immunolabelled. In extremely altered tissue PV-, CB-ir neurons cannot be detected, whereas the number of CR-ir somata is not reduced. The data indicate that subpopulations of interneurons of the CC may be differentially damaged. The alterations observed in the SP may implicate a possible impairment of transient neuronal circuitries that are essential for the development of cortical connections. On the whole, these neuronal alterations may account for residual deficits observed after shunting.