Paget's osteodystrophia deformans is a monoostotic or polyostotic disease of the skeletal system with increased bone remodelling, structural modifications and skeletal deformation, typically arranged like a chessboard. The unusual case of a patient is described who had suffered from generalized Paget's disease of the bone for 14 years and also developed progressive myopathy and a behavioural variant frontotemporal dementia. Further cytogenetic diagnostics revealed a point mutation in the valosin-containing protein (VCP, p97) gene on chromosome 9p13-p12 consistent with the finding of inclusion body myopathy with early onset Paget's disease and frontotemporal dementia (IBMPFD syndrome). A causal therapy of this disease is not known. Conservative treatment with bisphosphonate therapy, intensive physiotherapeutic exercise and psychotherapeutic treatment was performed to retard the progression of the disease.

Der Morbus Paget (Osteodystrophia deformans) ist durch eine lokale Steigerung des Knochenstoffwechsels, strukturelle Veränderungen sowie eine Verformung der betroffenen Skelettabschnitte charakterisiert. Typischerweise manifestiert sich diese Erkrankung an einem oder wenigen Knochen mit dann schachbrettartigem Befallsmuster. Dargestellt wird der ungewöhnliche Krankheitsverlauf eines Patienten mit einem nahezu generalisierten Knochenbefall bei Morbus Paget über einen Zeitraum von 14 Jahren. Zusätzlich konnten bei dem Patienten ein myopathisches Gewebesyndrom vom Gliedergürteldystrophietyp und eine frontotemporale Psychopathie nachgewiesen werden. Eine erweiterte humangenetische Diagnostik zeigte eine Punktmutation im VCP- („valosin-containing protein“-p97)-Gen auf Chromosom 9p13-p12, passend zu einem IBMPFD-Syndrom („inclusion body myopathy with early-onset Paget disease and frontotemporal dementia“). Eine kausale Therapie dieses Syndroms ist nicht bekannt. Durch symptomatische Behandlung mit Bisphosphonaten, Krankengymnastik sowie Psychotherapie konnten die Beschwerden des Patienten gelindert und das Fortschreiten der Erkrankung verlangsamt werden.

OBJECTIVE:Primary myoadenylate deaminase deficiency (MADD) is probably the most frequent inborn metabolic myopathy with a prevalence of up to 2%. It is the result of mutations in the AMPDI gene, the most common of which is a C34-T transition in exon 2. The importance of the more rare mutation G468-T in exon 5 is uncertain. Primary objective was to elucidate the clinical significance of the enzyme disorder, which remains unclear since its first description in 1978. We further examined the existence of an association of MADD with other muscle disorders, such as malignant hyperthermia and rhabdomyolysis, as was suspected in earlier studies.MATERIAL AND METHODS:In a large collection of 1673 muscle biopsies that had been stored deep frozen we identified 33 cases of primary MADD, 12 of which without any other coinciding muscle diseases, by histochemical, biochemical and molecular genetic examinations. Clinical and laboratory data was collected. By additional examination of randomly chosen blood samples we identified one person carrying the rare compound heterozygosity C34-T/ G468-T, who was examined in clinical respects and a muscle biopsy was taken.RESULTS:As underlying mutation, the most common transition C34-T/C 143-T was detected in 33 cases. One patient carried the compound heterozygosity C34-T/G468-T. The overall frequency of MADD in the contingent was 1.8%. Only three patients out of 12 with isolated primary MADD suffered from muscle complaints, one of whom did not experience the typical symptoms of exercise related myalgia, muscle cramps and weakness as described by Fishbein. The patient carrying C34-T/G468-T was a fully healthy female. She had never experienced any muscle complaints. Any association with other neuromuscular disorders, if not completely ruled out, was found to be very unlikely.CONCLUSION:The results suggest that MADD itself is unlikely to be solely responsible for the manifestation of muscular symptoms. It is probable that either the loss of a compensation mechanism or coexistent disturbances in muscle metabolism which are unidentified so far are required for the emergence of complaints.

Summary. A 74‐year‐old man with diabetes mellitus type II, retinopathy and polyneuropathy suffered from exophthalmus, ptosis and diplopia. Magnetic resonance imaging and computer tomography showed a space‐occupying process in the right orbital apex. An extranasal ethmoidectomy accompanied by an orbitotomia revealed the presence of septated hyphae. Aspergillus fumigatus was grown from the tissue. After surgical removal of the fungal masses, therapy with amphotericin B (1 mg kg −1 body weight) plus itraconazole (Sempera ® , 200 mg per day) over 6 weeks was initiated. Five months later the patient's condition deteriorated again, with vomiting, nausea and pain behind the right eye plus increasing exophthalmus. Antifungal therapy was started again with amphotericin B and 5‐fluorocytosine. Neutropenia did not occur. The patient became somnolent and deteriorated, a meningitis was suggested. Aspergillus antigen (titre 1 : 2, Pastorex ® ) was detected in liquor. Anti‐ Aspergillus antibodies were not detectable. Both the right eye and retrobulbar fungal masses were eradicated by means of an exenteratio bulbi et orbitae. However, renal insufficiency and an apallic syndrome developed and the patient died. At autopsy, a mycotic aneurysm of the arteria carotis interna dextra was detected. The mycotic vasculitis of this aneurysm had caused a rupture of the blood vessel followed by a massive subarachnoidal haemorrhage. In addition, severe mycotic sphenoidal sinusitis and aspergillosis of the right orbit were seen, which had led to a bifrontal meningitis.

The occasional observation of neurogenic features in oculopharyngeal muscular dystrophy (OPMD) is unclear both in nosological and in etiological respects. Studies are reported here of a family with autosomal-dominant OPMD involving seven members over three generations. In three of them muscle biopsies were performed. Two of the patients (a 45-year-old sister and a 57-year-old brother of the third generation) were studied in more detail and, in addition to the typical changes of OPMD, showed a neurogenic component both by electrophysiology and morphology. Molecular genetic investigations revealed a repeat unit of (GCG/GCA)13 in the first exon of the poly(A)binding-protein2 gene in both siblings. A possible association of this unusually long triplet repeat extension with the atypical phenotype is considered and has to be verified in other cases.

The authors report the case of a 10-year-old girl with intervertebral disc calcifications from the levels C6/C7 to Th1/Th2, presenting with a herniated calcified intervertebral disc at the C7/Th1 level, causing spinal cord compression with subsequent progressive paresis and sensory loss of her left leg. After anterior cervical discectomy and fusion the neurological deficits completely resolved within 2 weeks. It can be concluded that calcification of an intervertebral disc is a rare syndrome in childhood, causing progressive neurological deficit only in a few reported cases. Although the treatment of choice is conservative, surgery is required in patients who develop progressive neurological deficit.

BACKGROUND AND PURPOSE:Length of survival of patients with low-grade glioma correlates with the extent of tumor resection. These tumors, however, are difficult to distinguish intraoperatively from normal brain tissue, often leading to incomplete resection. Our goal was to evaluate the effectiveness of intraoperative MR guidance in achieving gross-total resection.METHODS:We studied 12 patients with low-grade glioma who underwent surgery within a vertically open 0.5-T MR system. During surgery, localization of residual tumor tissue was guided by interactive, near real-time imaging. The amount of residual tumor tissue on MR images was evaluated at the point of the operation at which the neurosurgeon would have terminated the procedure under conventional conditions (first control) and again before closing the craniotomy.RESULTS:Significant residual tumor (more than 10% of original tumor volume) was shown in eight patients at the first control condition. The percentage of resection varied from 26% to 100% (mean, 68%) at this time. Twelve tissue samples from seven patients were obtained in areas identified as residual tumor on MR images. In 10 cases, the neuropathologic investigation confirmed the presence of residual low-grade glioma; in two cases, the borderzone of tumor was identified. In evaluating the final sets of images, we found total resection in six cases, over 90% resection in five cases, and 85% resection in one case (mean, 96%).CONCLUSION:Surgical treatment of low-grade gliomas under intraoperative MR guidance provides improved resection results with maximal patient safety.

We report a unique case of a man suffering from chronic myelogenous leukaemia who presented with clinical symptoms, X-ray, and bronchoscopical findings consistant with a bronchopulmonary space-occupying process which was suspected to be a central lung carcinoma as a secondary de novo malignancy. In addition, the patient developed several subcutaneous nodular livid red lesions on the left forearm which were considered to be cutaneous metastases of the presumptive lung malignancy. Treatment was started with percutaneous radiation of the mediastinum over a period of ten days with a total dose of 25 Gray. The patient died from circulatory and respiratory failure. Only post mortem pathological examination was indicative of a nocardiosis of the lungs with haematological spread to eosophagus, pleura, and subcutaneous skin of the left forearm. Unfortunately, diagnosis of nocardiosis could not finally proven by culture or molecular biological methods. A lung carcinoma or an infiltrate of residual or relapsing chronic myelogenous leukemia in the lung could be definitely ruled out.

DNA-cytophotometry is one of the methods that may contribute to a more precise evaluation of the biological behaviour of tumours in addition to the WHO-classification. In this study 121 tumour specimens of 50 patients suffering from gliomas with one or up to three recurrencies were investigated. In all cases the histological type and WHO-grade and the Ki-67/MIB1 labeling index were determined. DNA cytophotometry was performed after single cell preparation on Feulgen-stained preparations, and the following parameters were calculated: stemline ploidy, 5c-exceeding rate, and 2c-deviation index. Statistical evaluation revealed a highly significant correlation between recurrence-free interval and WHO-grade only. The DNA parameters, however, furnished additional information about increasing genetic instability in the majority of the recurrencies independently of changes in the WHO-grade. They thus seem to be useful as additional parameters for the determination of glioma progression.

Intracranial lipomas located in the cerebellopontine angle are extremely rare. These tumours are maldevelopmental lesions which can cause slowly progessive neurological symptoms. The clinical management of these tumours differs significantly from other lesions in this region. A 27 year old woman presented with a 2-month history of vertigo and a slowly progressive deterioration of hearing in the left ear. Computed tomography (CT) revealed a large low-density mass in the left cerebellopontine angle without any contrast-enhancement. In T1-weighted magnetic resonance imaging (MRI) the lesion was hyperintense and did not enhance after application of gadolinium. Areas of lower signal intensity inside of the lesion were suggested as incorporated cranial nerves. A left retrosigmoidal approach in a semi-sitting position was chosen to expose the tumour. After reducing the tumour mass, the tumour was dissected from the cranial nerves which were incorporated into the tumour. The residual tumour was adherent to the brain stem and the encased lower cranial nerves, allowing only a near subtotal resection of the highly vascularized tumour in order to avoid neurological deficits. The histological examination revealed a lipoma. Attempts at complete removal of cerebellopontine angle lipomas usually result in severe neurological deficits. Conservative treatment should therefore be prefered. Limited surgery is indicated if the patients suffer from disabling neurological symptoms and signs e.g., vertigo, nausea, trigeminal neuralgia, facial weakness or facial spasm.

Zusammenfassung Eine genaue Bestimmung der biologischen Wertigkeit glialer Tumoren erfordert über die WHO-Klassifikation hinaus die Entwicklung und den Einsatz von Spezialmethoden, wozu auch die DNA-Zytophotometrie gehört. In der vorliegenden Studie wurden an insgesamt 121 histopathologisch klassifizierten Proben von Gliomen bei 50 Patienten mit mindestens 1 und bis zu 3 Rezidiven eine Reihe von DNA-Parametern (Stammlinienploidie, 5c-exceeding rate, 2c-deviation index) nach Zellvereinzelung und Feulgen-Reaktion mittels statischer Feulgen-DNA-Zytometrie bestimmt. Daneben wurde die Proliferationsaktivität (immunhistochemischer Ki-67/MIB-1-labeling index) morphometrisch ermittelt. Diese Parameter wurden mit den WHO-Graden und der Länge der rezidivfreien Intervalle statistisch verglichen. In den Rezidiven sowohl mit ansteigendem als auch mit gleichbleibendem WHO-Grad fand sich eine statistisch signifikante Zunahme des 2c DI, der 5c ER und des Ki-67/MIB-1 LI. Dabei ergab sich eine hochsignifikante Korrelation zwischen den WHO-Graden und der Länge der rezidivfreien Intervalle p <0,00001). Eine statistisch signifikante Korrelation zwischen den DNA- bzw. Proliferationsparametern ließ sich zur Länge des rezidivfreien Intervalls nicht, zum WHO-Grad nur im Falle der ersten Rezidive für die DNA-Parameter herstellen. Die Ergebnisse bestätigen die hohe prognostische Relevanz des WHO-Grades. Die Bestimmung der DNA-Parameter liefert insbesondere bei gleichbleibendem WHO-Grad zusätzliche Informationen über die zunehmende genetische Instabilität des Tumors, welche wie die zunehmende Proliferationsaktivität für die weitere Tumorprogression von Bedeutung ist.

The purpose of our study was to evaluate the feasibility and accuracy of brain biopsies performed within a vertically opened MR system. We worked with the interventional 0.5-T MR "SIGNA SP" (General Electric Medical Systems, Milwaukee, Wis.) with an integrated tracking device "Flashpoint Position Encoder" (Image Guided Technologies, USA). As a holding device for this instrument we constructed a special frame. The whole system allows an exact adjustment of an optimum biopsy direction and guidance of the biopsy in a non-stereotactic, interactive mode in near real-time. As biopsy tools we used MR-compatible aspiration and specially made side-cut needles (Daum, Germany; E-Z-EM, USA). We performed a prospective diagnostic brain biopsy study in 18 patients. Guidance of the needle was carried out using gradient-echo single-slice technique. The sample was taken after controlling the exact position of the needle tip on spin-echo images. In 12 cases an exact neuropathological diagnosis was possible. In 6 cases of negative biopsy (4 aspiration biopsies) the samples were not representative. Our results demonstrate the feasibility of interactive MR-guided minimally invasive brain biopsies in an open MR system. The best results were achieved using cut needles for biopsies of contrast-enhancing lesions visible on T1-weighted gradient-echo guidance sequence.

Zusammenfassung Bei der intraoperativen Kontrolle von Hirntumorresektionen in offenen MRT-Geräten kann es zu operativ induzierten Veränderungen, insbesondere Rand-enhancement-Zonen, kommen. Diese können Tumorreste vortäuschen, so daß die Radikalität des Eingriffs unterschätzt wird oder nicht tumortragende Hirnareale entfernt werden. Ergebnisse und Diskussion: Anhand von 42 in einem offenen 0,5-T-MRT (Signa SP, GE) vorgenommenen, biopsiekontrollierten Hirntumoroperationen werden Erscheinungsbild und Entstehungsweise der Randveränderungen analysiert. Bei den häufig vorzufindenden Rand-enhancement-Zonen handelt es sich um eine Überlagerung von präformierten Tumorrandreaktionen mit Mikrokontusionen. Die Ausbildung dieser Veränderungen braucht eine Mindestzeit von 10–15 min. Die ständige Analyse der die Tumorresektion begleitenden MRT-Kontrollen durch den Operateur und einen mit der Problematik vertrauten Radiologen gestattet in der Regel die Differenzierung der operativ induzierten Veränderungen und erhöht damit die Sicherheit des Eingriffs.

During MRI-controlled resection of brain tumors using an open MRI system, operation-induced alterations may occur, especially enhancement of the resection cavity wall. This may simulate tumor areas, resulting in false assessment of the resection or resection of non-tumorous areas. Based on 42 MRI- and biopsy-controlled brain tumor resections in an 0.5 T open MRI (Signa SP, GE), the appearance and origin of operation-induced reactions are analyzed. In our opinion, there is a superposition of preformed peritumoral reactions by operation-induced microcontusions. The beginning of the cavity wall enhancement needs at least 10-15 min. MRI-controlled analysis of the intraoperative steps by the neurosurgeon and neuroradiologist allows discrimination of operation-induced reactions from tumor areas and leads to safe operation.

Summary. We report on a man suffering from chronic myelogenous leukaemia treated by allogeneic bone marrow transplantation who, in the late post‐transplantation phase, developed a hyperacute fatal invasive rhinocerebral zygomycosis. The origin of the ascending infection was the sinus sphenoidalis from which fungal hyphae spread to the central nervous system via the skull and the dura mater. The first symptoms of this severe infection were cerebral convulsions and a bilateral total amaurosis. The isolation of the pathogen from post mortem tisue was not successful. The present case is compared with previous reports of zygomycoses after bone marrow transplantation.Zusammenfassung. Ein Mann mit chronisch myeloischer Leukämie wurde knochenmarktransplantiert und entwickelte in der späten Posttransplantationsphase eine hyperakute, fatale invasive rhinozerebrale Zygomykose. Der Ursprung der aufsteigenden Infektion war der Sinus sphenoidalis, von dem aus sich Pilzhyphen über die Schädelbasis und die Dura mater in das Zentralnervensystem ausbreiteten. Erstsymptome dieser schweren Infektion waren zerebrale Krampfanfälle und eine bilaterale Amaurose. Die kulturelle Isolierung des Erregers aus Autopsiematerial gelang nicht. Der vorliegende Fall wird mit anderen Kasuistiken von Zygomykosen nach Knochenmarktransplantation verglichen.