Lhermitte-Duclos disease (Dysplastic gangliocytoma of the cerebellum).

OBJECTIVE: Dysplastic gangliocytoma of the cerebellum (Lhermitte-Duclos disease) is a rare hamartomatous lesion of the cerebellar cortex. The pathogenesis of the disease is still poorly understood. Lhermitte-Duclos disease was recently considered to be part of a multiple hamartoma-neoplasia syndrome (Cowden disease). We add two further cases to this rare entity. PATIENTS: A 24-year old woman presented with occipital headaches, blurred vision, diplopia and ataxia of gait. Physical examination revealed turricephaly. The second patient was a 37-year old woman, who presented with progressive occipital headache with nausea and vomiting. Physical examination revealed congenital facial asymmetry. Computed tomography and NMR-imaging, respectively demonstrated a space occupying mass of a cerebellar hemisphere in both cases. RESULTS: Suboccipital craniotomy and complete removal of the infratentorial tumour were performed in both patients. Histopathological findings clinched the diagnosis of Lhermitte-Duclos disease. Postoperative course was uneventful in the first and complicated by progressive occlusive hydrocephalus in the second patient, necessitating permanent surgical shunt drainage. Both patients were discharged free of complaints. CONCLUSIONS: Dysplastic cerebellar gangliocytoma is commonly associated with progressive mass effects in the posterior fossa and typically presents with headaches, cerebellar dysfunction, occlusive hydrocephalus and cranial nerve palsies. The disease usually manifests in young adults, but the age at presentation ranges from birth to the sixth decade. There is no sex predilection. NMR-imaging became a useful clue to the diagnosis within the last decade. Therapy consists of decompression of the posterior fossa by total surgical removal of the tumour mass.

Effect of fibrinogen substitution in afibrinogenemia on hemorheology and platelet function.

Fibrinogen substitution can correct bleeding in afibrinogenemia. We assessed the effect of fibrinogen substitution in a patient lacking immunoreactive fibrinogen. Fibrinogen and thrombin time were not measurable before, but became detectable within 30 min after substitution, parallelled by an increase in ADP-induced platelet aggregation from < 10% to 32%. Platelet adhesion, measured by Stagnation Point Flow Adhesio- Aggregometry, was not detectable prior to substitution but attained normal values thereafter. Scanning electron microscopy of adhering platelets revealed pseudopodia protrusion and spreading. Morphometry revealed two populations of spread platelets one of which demonstrated inhibited spreading as compared to healthy controls. Immunoelectron microscopy revealed normal GPIIb/IIIa receptor expression, both before and after substitution. Dynamic and kinematic viscosity of plasma and whole blood remained below the 99.9% confidence border of a healthy control group. In afibrinogenemia fibrinogen levels as low as 10% of normal concentration sufficed to normalize coagulation, platelet adhesion, and, partially, spreading.

Demonstration of herpes simplex virus DNA in CSF cells by in situ hybridization for early diagnosis of herpes encephalitis.

Herpes simplex virus (HSV) was studied by in situ DNA hybridization with a biotinylated cDNA probe in 56 air-dried methanol-fixed cerebrospinal fluid (CSF) cell preparations which had been collected from 12 patients with herpes simplex encephalitis (HSE) during the previous 5 years. In three additional HSE cases, freshly prepared acetone-fixed CSF cell preparations were available. In all cases, CSF cell preparations were obtained by cytocentrifugation. Herpes simplex virus DNA could be demonstrated in 8 of the 12 HSE cases with methanol-fixed cells (66%) and in all 3 cases with fresh acetone-fixed CSF cells. The earliest CSF sample was available at the onset of symptoms and showed positive DNA hybridization. In three cases hybridization was positive after a clinical course of more than 5 weeks but was usually found in the 1st week of illness before the beginning of specific inthrathecal IgG synthesis. In 54 control cases with other acute inflammatory diseases of the CNS, including 14 cases of varicella-zoster meningitis, no positive hybridization was detected. These findings strongly suggest that in situ hybridization in CSF cells is a reliable tool for the early and rapid diagnosis of HSE, especially at the onset of the disease, when no antibodies can be detected.

Recovery patterns of rat hemopoietic stem cells between pulse doses of 7,12-dimethylbenz(a)anthracene (DMBA) applied in a leukemogenic regimen.

Male Wistar rats received repeated pulse doses of 7,12-dimethylbenz(a)anthracene (DMBA), known to elicit myelodysplasia followed by acute, mostly erythroblastic, leukemia at 10-day intervals. The recovery of spleen colony forming hemopoietic stem cells (CFU-s) surviving the cytocidal action of DMBA was examined between pulses. Recovery after a pulse of 35 mg/kg body weight varied with the organ source of the CFU-s (femoral bone marrow or spleen) and the number of preceding DMBA pulses. After a single DMBA pulse bone marrow CFU-s initially recovered faster than reported for normal bone marrow CFU-s transplanted into chemically conditioned rats. But recovery was followed by regeneration arrest. Population doubling times of marrow CFU-s increased with the number of DMBA pulses. Recovery of splenic CFU-s was slower after a single DMBA pulse than reported for normal spleen CFU-s transplanted into chemically conditioned rats. The CFU-s population doubling times were not significantly different after a single or five DMBA pulses. After three pulses, however, recovery of splenic CFU-s was exceedingly slow until day 5 and subsequently accelerated, but was still slower than after one or five pulses. In the spleen CFU-s recovery was always accompanied by regeneration of total cell numbers with a preference for erythroid regeneration. In the bone marrow this was the case after three DMBA pulses only.

S-phase resistance of rat hematopoietic stem cells to 7,12-dimethylbenz(a)anthracene cytocide and its implications for leukemia development.

In the experimental rat leukemia system, induced by repeated 7,12-dimethylbenz(a)anthracene (DMBA) pulses, the sensitivity of the spleen colony-forming hematopoietic stem cells (CFU-s) to the cytocidal action of a challenging DMBA injection (35 mg/kg body weight) varied with the number of pulses already applied and the organ source of CFU-s (femoral bone marrow or spleen). Assessment of the fraction of DNA-synthesizing CFU-s with the [3H]thymidine suicide technique at the time of DMBA challenge and comparison with the 20-hr CFU-s reduction values by DMBA in vivo showed an inverse correlation (p less than 0.001). It was deduced, therefore, that S-phase CFU-s are relatively resistant to DMBA cytocide. Since initiation by chemical carcinogens has been shown to be relatively S-phase specific, S-phase-resistant cytocide would lead to a selection of initiated cells and, in the case of repeated applications, to a selection of cells with multiple successive initiation hits. Preferential differentiation and organ site of leukemia, as well as evolution in sequential morphological steps, fit this assumption.