Isolated lympho-histiocytic inflammation of the Gasserian ganglion mimicking trigeminal schwannoma.

UNLABELLED: We present an unusual case of a patient with trigeminal pain and hypesthesia suggesting trigeminal schwannoma, where histology demonstrated an inflammatory lesion of the Gasserian ganglion. CLINICAL PRESENTATION: Patient history and imaging were typical for a trigeminal schwannoma with a dumbbell growth in the middle and posterior fossa. Surgery was performed and resection of a firm mass intermingled with fascicles originating from the ganglion and the mandibular branch was carried out via a subtemporal approach. Histological diagnosis revealed a non-caseating, vaguely granulomatous lymphocyte- and histiocyte-rich inflammation. CONCLUSION: Inflammatory lesions of the Gasserian ganglion are rare but may mimic tumors. Intraoperative biopsies should be taken prior to complete resection to limit neurological deterioration.

Imaging of human brain tumor tissue by near-infrared laser coherence tomography.

INTRODUCTION: Intraoperative detection of residual tumor remains an important challenge in surgery to treat gliomas. New developments in optical techniques offer non-invasive high-resolution imaging that may integrate well into the workflow of neurosurgical operations. Using an intracranial glioma model, we have recently shown that time domain optical coherence tomography (OCT) allows discrimination of normal brain, diffusely invaded brain tissue, and solid tumor. OCT imaging allowed acquisition of 2D and 3D data arrays for multiplanar analysis of the tumor to brain interface. In this study we have analyzed biopsy specimens of human brain tumors and we present the first feasibility study of intraoperative OCT and post-image acquisition processing for non-invasive imaging of the brain and brain tumor. METHODS: We used a Sirius 713 Tomograph with a superluminescence diode emitting light at a near infrared central wavelength of 1,310 nm and a coherence length of 15 microm. The light is passed through an optical mono mode fiber to a modified OCT adapter containing a lens system with a working distance of 10 cm and an integrated pilot laser. Navigation-registered tumor biopsies were imaged ex vivo and the intraoperative site of optical tissue analysis was registered by marker acquisition using a neuronavigation system. RESULTS: Optical coherence tomography non-contact measurements of brain and brain tumor tissue produced B-scan images of 4 mm in width and 1.5-2.0 mm in depth at an axial and lateral optical resolution of 15 microm. OCT imaging demonstrated a different microstructure and characteristic signal attenuation profiles of tumor versus normal brain. Post-image acquisition processing and automated detection of the tissue to air interface was used to realign A-scans to compensate for image distortions caused by pulse- and respiration-induced movements of the target volume. Realigned images allowed monitoring of intensity changes within the scan line and facilitated selection of areas for the averaging of A-scans and the calculation of attenuation coefficients for specific regions of interest. CONCLUSION: This feasibility study has demonstrated that OCT analysis of the tissue microstructure and light attenuation characteristics discriminate normal brain, areas of tumor infiltrated brain, solid tumor, and necrosis. The working distance of the OCT adapter and the A-scan acquisition rate conceptually allows integration of the OCT applicator into the optical path of the operating microscopes. This would allow a continuous analysis of the resection plain, providing optical tomography, thereby adding a third dimension to the microscopic view and information on the light attenuation characteristics of the tissue.

A non-midline spheno-orbital encephalocele in a newborn.

Basal encephaloceles in western countries occur in 1 of every 35 000-40 000 live births; with an incidence of less than 10% they are the least common of all encephaloceles. Certain subtypes such as transsphenoidal variants may be as rare as 1 in 700 000 live births. These rare encephaloceles are classified into five anatomic types: spheno-ethmodial, transsphenoidal, spheno-orbital, transethmoidal, and spheno-maxillary. Here we present an exceedingly rare variant of a non-midline basal encephalocele of the spheno-orbital type, which was treated by resection of the encephalocele, which contained dysplastic central nervous system tissue, on day four post partum. The patient had no neurological deficits and a six year follow-up showed a normal intellect and a good cosmetic result.

Time-domain and spectral-domain optical coherence tomography in the analysis of brain tumor tissue.

INTRODUCTION: Detection of residual tumor during resection of glial brain tumors remains a challenge because of a low inherent contrast of adjacent edematous brain, the surrounding infiltration zone, and the solid tumor. Therefore, new technologies that may facilitate an intraoperative analysis of the tissue at the resection edge are of great interest to neurosurgeons. MATERIALS AND METHODS: For ex vivo imaging of gliomas in a mouse model and human biopsy specimens of brain tumors and nervous system tissue we have used a time-domain Sirius 713 Tomograph with a central wavelength of 1,310 nm and a coherence length of 15 microm equipped with a mono mode fiber and a modified optical coherence tomography (OCT) adapter containing a lens system for imaging at a working distance of 2.5 cm. A spectral-domain tomograph using 840 nm and 930 nm superluminescence diodes (SLD) with a central wavelength of 900 nm was used as a second imaging modelity. RESULTS: Both time-domain and spectral-domain coherence tomography delineated normal brain, the infiltration zone and solid tumor in murine intracerebral gliomas. Histological evaluation of H&E sections parallel to the optical plain demonstrated that tumor areas of less than a millimeter could be detected and that not only solid tumor, but also brain invaded by a low-density single tumor cells produced an OCT signal different from normal brain. Spectral-domain OCT (SD-OCT) demonstrated a significantly more detailed microstructure of tumor and normal brain up to a tissue depth of 1.5-2.0 mm, whereas the interpretation of time-domain OCT (TD-OCT) was difficult at a tissue depth >1.0 mm. Because of rapid scanning times SD-OCT data could be acquired as 3D data maps, which allowed a multi-planar analysis of the tumor to brain interface. Similar to our findings in experimental gliomas, images of human nervous system tissue acquired using SD-OCT showed a characteristic signal of normal brain tissue and a detailed microstructure of tumor parenchyma. CONCLUSION: Spectral-domain OCT of experimental gliomas and human brain tumor specimens differentiates solid tumor, diffusely invaded brain tissue, and adjacent normal brain based on microstructure and B-scan signal characteristics. In conjunction with the rapid image acquisition rates of SD-OCT, this technology carries the potential of a novel intraoperative imaging tool for the detection of residual tumor and guidance of neurosurgical tumor resections.

Spinocerebellar ataxia type 4 (SCA4): Initial pathoanatomical study reveals widespread cerebellar and brainstem degeneration.

Spinocerebellar ataxia type 4 (SCA4), also known as 'hereditary ataxia with sensory neuropathy', represents a very rare, progressive and untreatable form of an autosomal dominant inherited cerebellar ataxia (ADCA). Due to a lack of autopsy cases, no neuropathological or clinicopathological studies had yet been performed in SCA4. In the present study, the first available cerebellar and brainstem tissue of a clinically diagnosed and genetically-confirmed German SCA4 patient was pathoanatomically studied using serial thick sections. During this systematic postmortem investigation, along with an obvious demyelinization of cerebellar and brainstem fiber tracts we observed widespread cerebellar and brainstem neurodegeneration with marked neuronal loss in the substantia nigra and ventral tegmental area, central raphe and pontine nuclei, all auditory brainstem nuclei, in the abducens, principal trigeminal, spinal trigeminal, facial, superior vestibular, medial vestibular, interstitial vestibular, dorsal motor vagal, hypoglossal, and prepositus hypoglossal nuclei, as well as in the nucleus raphe interpositus, all dorsal column nuclei, and in the principal and medial subnuclei of the inferior olive. Severe neuronal loss was seen in the Purkinje cell layer of the cerebellum, in the cerebellar fastigial nucleus, in the red, trochlear, lateral vestibular, and lateral reticular nuclei, the reticulotegmental nucleus of the pons, and the nucleus of Roller. In addition, immunocytochemical analysis using the anti-polyglutamine antibody 1C2 failed to detect any polyglutamine-related immunoreactivity in the central nervous regions of this SCA4 patient studied. In view of the known functional role of affected nuclei and related fiber tracts, the present findings not only offer explanations for the well-known disease symptoms of SCA4 patients (i.e. ataxic symptoms, dysarthria and somatosensory deficits), but for the first time help to explain why diplopia, gaze-evoked nystagmus, auditory impairments and pathologically altered brainstem auditory evoked potentials, saccadic smooth pursuits, impaired somatosensory functions in the face, and dysphagia may occur during the course of SCA4. Finally, the results of our immunocytochemical studies support the concept that SCA4 is not a member of the CAG-repeat or polyglutamine diseases.

A new collagen biomatrix of equine origin versus a cadaveric dura graft for the repair of dural defects--a comparative animal experimental study.

OBJECT: Numerous types of materials have been evaluated over the past decades in the quest for the ideal dural replacement, but no product fully meets all the applicable criteria. This paper presents the long-term results of an animal trial of a collagen biomatrix (TISSUDURA, Baxter AG, Vienna/Austria) for the repair and regeneration of dural defects. This product provides a matrix with a special layer structure and consists of pure naturally cross-linked collagen of equine origin. The comparable material is Tutoplast Dura, a human cadaveric-derived dural graft preserved in a multiple stage chemical process. METHODS: Bihemispheric parietotoccipital dural defects of a defined size were induced in 25 sheep and subsequently closed with the collagen graft or Tutoplast Dura, respectively. RESULTS: Postoperative neurological abnormalities did not occur in any animal. There were no signs of graft rejection or formation of cerebrospinal fluid fistulae. The collagen graft site displayed histological signs as early as 2 weeks postoperatively consistent with a moderate Iymphocytic inflammatory response and infiltration with fibroblasts and macrophages. The graft subsequently developed a neodura-like connective tissue architecture. The Tutoplast Dura showed only minimal cellular infiltration, and again the surrounding structures displayed a mild inflammatory response. 24 weeks postoperatively, the dura and neomembrane were barely distinguishable at the collagen biomatrix site, but the Tutoplast Dura displayed inadequate fusion with the dural border and was encapsulated in a connective tissue layer. CONCLUSION: The outcomes demonstrate that the collagen graft can be used for dura reconstruction as a temporary dural replacement and at the same time as a biomatrix for dural regeneration.

Signs of rapidly progressive dementia in a case of intravascular lymphomatosis.

Intravascular lymphomatosis (IVL), a rare type of non-Hodgkin's lymphoma, is an uncommon cause of progressive dementia, usually followed by death within a few months of onset of clinical disease. Often this aggressive tumor is only diagnosed at autopsy, because of misleading clinical features mimicking a broad spectrum of syndromes and the absence of circulating lympoma cells in the blood, bone marrow or cerebrospinal fluid in many cases. Here we present IVL in a 78-year-old woman with findings leading to the clinical diagnosis of vascular dementia with sudden beginning and positive 14-3-3 protein in the CSF, commonly reported in Creutzfeldt-Jakob disease (CJD).

Ivemark syndrome with agenesis of the corpus callosum: a case report with a review of the literature.

Asplenia associated with situs ambiguus, symmetric liver, bilateral trilobulated lungs, and a complex heart defect was diagnosed on autopsy in a 14-day-old infant. Furthermore, examination of the brain displayed agenesis of the corpus callosum (ACC) with pachygyria and hydrocephalus. The characteristic association of asplenia with visceroatrial heterotaxia is traditionally named after the Swedish pediatrician, Ivemark. Although exceptional, association of Ivemark syndrome with callosal agenesis has been reported recently. The concept of 'developmental fields' describes morphogenetically reactive units of the embryo determining and controlling the development of complex structures in a hierarchical manner. Lateralization defects such as situs inversus, asplenia or polysplenia due to defective left-right axis development, as well as decussation defects such as ACC, are considered as defects of the primary developmental field. Therefore, additional callosal agenesis in Ivemark syndrome may be a coherent and synchronic defect in the primary developmental field rather than a causally independent malformation.

Dementia in patients undergoing long-term dialysis: aetiology, differential diagnoses, epidemiology and management.

Dementia in patients undergoing long-term dialysis has not been clearly defined; however, four different entities have been described. Uraemic encephalopathy is a complication of uraemia and responds well to dialysis. Dialysis encephalopathy syndrome, the result of acute intoxication of aluminium caused by the use of an aluminium-containing dialysate, was a common occurrence prior to 1980. However, using modern techniques of water purification, such acute intoxication can now be avoided. Dialysis-associated encephalopathy/dementia (DAE) is always associated with elevated serum aluminium levels. Pathognomonic morphological changes in the brain have been described, but the mechanism for the entry of aluminium into the CNS is incompletely understood. The mechanisms involved in the pathogenesis of the neurotoxicity associated with aluminium are numerous. Although only a very small fraction of ingested aluminium is absorbed, the continuous oral aluminium intake from aluminium-based phosphate binders, and also of dietary or environmental origin, is responsible for aluminium overload in dialysis patients. Age-related dementia, especially vascular dementia, occurs in patients undergoing long-term dialysis as frequently as it does in the general population. The differential diagnoses of dialysis-associated dementias should include investigation for metabolic encephalopathies, heavy metal or trace element intoxications, and distinct structural neurological lesions such as subdural haematoma, normal pressure hydrocephalus, stroke and, particularly, hypertensive encephalopathy and multi-infarct dementia. To prevent DAE, dietary training programmes should aim to achieve the lowest phosphate intake and pharmacological tools should be used to keep serum phosphate levels below 2 mmol/L. To prevent vascular dementia, lifestyle modification should be undertaken, including optimal physical activity and fat intake, nicotine abstinence, and targeting optimal blood glucose, cholesterol and triglyceride levels, and blood pressure, to those outlined in current recommendations.

Subacute fatal aluminum encephalopathy after reconstructive otoneurosurgery: a case report.

We report a 52-year-old woman who underwent otoneurosurgery to resect acoustic neurinoma. Bone reconstruction was performed with an aluminium (Al)-containing cement. Six weeks later the patient suffered from loss of consciousness, myoclonic jerks, and persistent grand mal seizures, clinical symptoms that resembled those of lethal dialysis encephalopathy of the 1960s and 1970s. She died 6 months later because of septic complications. Light- and electron-microscopic investigation of the central nervous system (CNS) showed pathognomonic Al-containing intracytoplasmic argyrophilic inclusions in choroid plexus epithelia, neurons, and cortical glia. These changes are characteristics of dialysis-associated encephalopathy (DAE), induced nowadays by long-term ingestion of Al-containing drugs (and with benign clinical courses). Atomic absorption spectrometry showed an increase of mean bulk Al concentration of the cortex and subcortex up to 9.3 microg/g (normal range <2 microg/g); laser microprobe showed the increase of Al in subcellular structures. This unique case again shows the extraordinary neurotoxicity of Al, which was, in our patient, initiated by an amount of about 30 mg Al and apparently caused by direct Al access to the brain parenchyma via a cerebrospinal fluid leakage.

Water-jet dissection in parotid surgery: an experimental study in dogs.

OBJECTIVE: The objective of the present study was to investigate the application of the water-jet dissection method in parotid surgery by way of animal experiments, paying particular attention to the clinical and histological reactions of the facial nerve. STUDY DESIGN: An animal experimental study. METHODS: Total bilateral parotidectomies with retention of the facial nerve were performed on 19 beagle dogs by means of the Hydro-Jet device (Andreas Pein Medizintechnik Company, Schwerin, Germany) using different jet diameters and operating pressures. All operations were performed with continuous intraoperative facial monitoring (Neurosign 100, Inomed Company, Teningen, Germany). The dogs were monitored postoperatively over an average period of 20.3 days (range, 14-35 d). Local findings and facial nerve status were documented daily. In a second phase, the dissected nerves were resected and the animals were killed. Samples of water-jet-dissected parotid tissue, as well as all dissected nerve branches, underwent histological examination and were compared with clinical and electrophysiological findings. RESULTS: It was possible to perform operations easily on all parotid glands by means of the Hydro-Jet using the small, 120-microm jet at operating pressures of 40 to 60 bar and to dissect the facial nerve quickly and safely with retention of its functional capability (n = 34). The dissection of nerves using larger-diameter jets (150 and 200 microm [n = 64]) resulted in a total of two reversible and seven irreversible partial pareses. CONCLUSIONS: The study has shown that it is possible to perform tissue-selective operations on the parotid gland by means of the Hydro-Jet using the 120-microm jet at operating pressures of 40 to 60 bar, ensuring safe, atraumatic dissection of the facial nerve with retention of its functional capability. The advantages of the new Hydro-Jet method offer a valuable alternative compared with the normal dissection methods adopted in parotid surgery. Thus the results of the present investigation currently are being checked within the framework of a clinical study at our clinic.

Alzheimer morphology is not increased in dialysis-associated encephalopathy and long-term hemodialysis.

This study examines the role of aluminium in the etiology of Alzheimer's disease (AD). Brains taken at autopsy (n = 50) from patients with a history of long-term hemodialysis (HD) and intake of aluminium (Al)-containing drugs were examined by light microscopy. Using our modified silver stain we have been able to demonstrate and clearly discriminate between AD changes and dialysis-associated encephalopathy (DAE) on paraffin sections; evaluation was done with a 3-point scale. DAE morphology is characterized by lysosome-derived intracytoplasmic, Al-containing, pathognomonic, argyrophilic inclusions in choroid plexus epithelia, cortical glia and neurons. A statistically significant difference was found between the amounts of drug-related Al ingested and the degree of DAE-related morphological change (P < 0.001). On the other hand no apparent microscopical increase in AD morphology was found. No AD changes were seen whatsoever in patients under the age of 60, despite a history of long-term HD with ingestion of "pure" Al up to 2.5 kg. Patients over 60 years of age occasionally presented with sparse deposits of beta A4 amyloid (beta A4) and/or a low incidence of AD-type neurofibrillary tangles (NFT). In accordance with CERAD criteria these were identified as normal, age-related phenomena (P < 0.001 for beta A4; P < 0.001 for NFT). Rare, isolated cases from a group of 127 long-term hemodialyzed patients have been reported previously, who presented with intermingled, clearly distinguishable lesions of both age-related AD morphology and DAE changes. Comparison of AD morphology with an age-matched control group was not statistically significant (P > 0.6 for beta A4, P > 0.7 for NFT). In our experience, Al does not cause an increase in AD morphology, at least not in terms of bioavailable Al in drugs or as a result of long-term HD.

[Endoscopic use of the water jet dissector in the cerebral ventricle system--an experimental study]. / Endoskopischer Einsatz des Water Jet Dissektors im Hirnkammersystem--eine experimentelle Studie.

Endoscopic surgery in the cerebral ventricle is limited by the small number of suitable instruments and bleedings obscuring the visibility. The water jet cutter allows the dissection of tissue, generally leaving vessels intact. Therefore it could be an additional instrument for neuroendoscopic purposes. In this preclinical study the employment of the water jet dissector under endoscopic conditions was evaluated. Incision-experiments (n = 80) on the ventricular system of fresh porcine brain were carried out under endoscopic view. To achieve similarity to the ventricular system, specimens were dissected in liquid medium (Ringer's-lactate, 37 degrees C). The depths of incision were measured digitally and histological examination of the tissue was performed. Depending on the applied pressure, distance from cutting nozzle to tissue and cutting velocity, the depths of incision ranged from 0.12 mm up to 2.4 mm. The water jet dissector is good to handle under endoscopic conditions and vessels are preserved. Based on these factors, this instrument is predestinated for further neuroendoscopic application. Prior to clinical application our results will have to be tested on living, perfused cerebral tissue.

Failure to detect Chlamydia pneumoniae in brain sections of Alzheimer's disease patients.

A recent North American study detected Chlamydia pneumoniae in 17 of 19 brains of Alzheimer's patients and supposed a C. pneumoniae infection to be a risk factor for Alzheimer's disease (AD). In this study, we analyzed paraffin-embedded tissue samples of 20 AD patients by nested PCR and immunocytochemistry with a panel of antichlamydial antibodies and could detect neither C. pneumoniae-specific DNA nor chlamydial antigens. From our data, the presence of C. pneumoniae in the brains of Alzheimer's patients is not a common phenomenon; an association remains questionable.

A cavernous hemangioma simulating an intracanalicular acoustic neurinoma--a case report.

A case of an intrameatal cavernous hemangioma is reported. The 53-year-old patient presented with decreased hearing and a slight 7th nerve palsy on the left. Clinical features and preoperative radiological appearances were indistinguishable from those of an acoustic neurinoma. Though, DD the involvement of all three nerves (N. facialis, N. cochlearis, N. vestibularis) should have lead to another entity. The tumour showed intraoperatively no relationship to the 8th cranial nerve, but was very adherent to the facial nerve. The macroscopic appearance differed to the usual aspect of an acoustic neurinoma. The final diagnosis was made after the operation with histopathological methods. The clinical features and pathology of this type of tumour are discussed.

Chordoid glioma of the third ventricle: immunohistochemical and molecular genetic characterization of a novel tumor entity.

Chordoid glioma of the third ventricle was recently reported as a novel tumor entity of the central nervous system with characteristic clinical and histopathological features (Brat et al., J Neuropathol Exp Neurol 57: 283-290, 1998). Here, we report on a histopathological, immunohistochemical and molecular genetic analysis of five cases of this rare neoplasm. All tumors were immunohistochemically investigated for the expression of various differentiation antigens, the proliferation marker Ki-67, and a panel of selected proto-oncogene and tumor suppressor gene products. These studies revealed a strong expression of GFAP, vimentin, and CD34. In addition, most tumors contained small fractions of neoplastic cells immunoreactive for epithelial membrane antigen, S-100 protein, or cytokeratins. The percentage of Ki-67 positive cells was generally low (<5%). All tumors showed immunoreactivity for the epidermal growth factor receptor and schwannomin/merlin. There was no nuclear accumulation of the p53, p21 (Waf-1) and Mdm2 proteins. To examine genomic alterations associated with the development of chordoid gliomas, we screened 4 tumors by comparative genomic hybridization (CGH) analysis. No chromosomal imbalances were detected. More focussed molecular genetic analyses revealed neither aberrations of the TP53 and CDKN2A tumor suppressor genes nor amplification of the EGFR, CDK4, and MDM2 proto-oncogenes. Our data strongly support the hypothesis that chordoid glioma of the third ventricle constitutes a novel tumor entity characterized by distinct morphological and immunohistochemical features, as well as a lack of chromosomal and genetic alterations commonly found in other types of gliomas or in meningiomas.

Tuberous sclerosis with intracardiac rhabdomyoma in a fetus with trisomy 21: case report and review of literature.

A large cardiac rhabdomyoma protruding into the left ventricle was diagnosed in a fetus at 21+2 weeks of gestation by grey-scale echocardiography. Obstruction to left ventricular outflow was ruled out by colour and spectral Doppler echocardiography. No other abnormalities were noted and karyotyping by cordocentesis revealed trisomy 21 (47,XY,+21). Post-mortem examination after termination of pregnancy confirmed the prenatal diagnosis of cardiac rhabdomyoma and in addition revealed fetal tuberous sclerosis. Demonstration of cardiac rhabdomyoma by prenatal ultrasound should raise suspicion of the presence of fetal tuberous sclerosis. Despite the incidental association with aneuploidy, fetal karyotyping is suggested for optimal counselling of parents.

[A long-term organic brain syndrome and brain stem symptoms in an undiagnosed dialysis-associated encephalopathy]. / Langjähriges Psychosyndrom und Hirnstammsymptomatik bei unerkannter Dialyse-assoziierter Enzephalopathie.

HISTORY AND CLINICAL FINDINGS: A 73-year-old woman in renal failure for the past 22 years had been on haemodialysis for 16 years. Because of hyperphosphataemia and peptic ulcers she had been on aluminium-containing antacids with a total intake over time of about 8 kg "pure" aluminium. Over the past 11 years she had biphasic symptoms of death anxieties and depression. She also had amnesic aphasia and some extrapyramidal symptoms as well as generalized convulsive seizures and recurrent falls. INVESTIGATIONS: Cranial computed tomography merely revealed signs of a microangiopathy and an age-related decrease in brain volume. The EEG showed intermittent changes while the CSF and ECG were unremarkable. There was no benzodiazepine or ethanol in the blood. TREATMENT AND COURSE: After excluding stroke with secondary epilepsy, uraemic encephalopathy was assumed to be the cause of the severe organic psychiatric syndrome. In the last few days before her death the patient had disturbance of consciousness and of breathing. She died during grotesque tossing movements, thought to be due to a brain stem stroke. Autopsy revealed high-grade myocardial hypertrophy caused by the hypertension, contracted kidney of vascular cause, hyperplasia of the parathyroid and calcification of the renal parenchyma as a sign of secondary parathyroidism. The CNS showed severe dialysis-associated encephalopathy with characteristic argyrophilic, aluminium-induced lysosomal intracytoplasmic inclusions in the choroid plexus epithelium, cortical glia and numerous neuron populations. Laser microprobe mass analysis (LAMMA) confirmed manifold increase in subcellular aluminium content, especially in the neuronal cytoplasm, also demonstrated by atom absorption spectrometry. Additional distinct deposition of beta A4-amyloid, typical of Alzheimer's disease, was probably age-related rather than associated with the dialysis and the aluminium uptake. CONCLUSION: Dialysis-associated encephalopathy must be taken into account as a possible cause of aetiologically uncertain neuropsychiatric symptoms in patients on chronic haemodialysis.

Familial pontocerebellar hypoplasia type I with anterior horn cell disease.

We report the association of pontocerebellar hypoplasia and anterior horn cell disease in three female siblings. One child presented with the classical clinical and neuropathological features of pontocerebellar hypoplasia with associated anterior horn cell disease, described by Barth as pontocerebellar hypoplasia type I. This patient showed polyhydramnios, congenital contractures, respiratory insufficiency, hypotonia, areflexia, listlessness and myoclonic seizures. Postmortem examination revealed a loss of neurons and reactive gliosis in the pontocerebellum and in addition anterior horn cell atrophy resembling Werdnig-Hoffmann disease. Another sibling demonstrated the same clinical symptoms. However neuropathological findings showed evidence for pontocerebellar hypoplasia only. The third sibling was examined after induced fetal abortion because of prenatally diagnosed arthrogryposis. Anterior horn cell disease was obvious histologically whereas pontocerebellar hypoplasia could not be demonstrated due to cerebral autolysis. The similar clinical and neuropathological findings in the three reported siblings suggest a common genetic defect with different patterns of pontocerebellar hypoplasia and associated anterior horn cell disease. The gene defect of this rare disorder is still unknown. The 'survival motor neuron' gene of spinal muscular atrophy was not found in these three siblings.