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Two unrelated patients with macrocephaly, seizures, and mild cerebellar signs had a dysplastic gangliocytoma of the cerebellum (Lhermitte-Duclos disease). Both also had autosomal dominant Cowden disease as evidenced by facial, oral, and acral papules. In the two families, 9 sibs demonstrated the mucocutaneous lesions, thyroid disease, breast tumors, and ovarian tumors compatible with the diagnosis of Cowden disease. Some of the sibs also showed various degrees of neurological signs such as macrocephaly, mental retardation, seizures, tremor, and dysdiadochokinesia. Magnetic resonance imaging scans of sibs of one family demonstrated megalencephaly and other mild abnormalities. The occurrence of these two rare disorders in single patients is more than a coincidence, and the clinical findings in the combined condition establishes it as a new phakomatosis.

The development and application of a procedure for interphase cytogenetics on brain tumor material is described. Nuclei isolated from freshly removed brain tumor tissue were investigated for chromosomal aberrations by nonradioactive in situ hybridization with a panel of chromosome-specific probes. The panel consisted of nine satellite DMA probes specific for the centromeric regions of chromosomes 1, 6, 7, 10, 11, 17, 18, X, and Y. For each probe, the number of hybridization signals per cell was determined in 200 nuclei. It was inferred from the hybridization results that in 11 gliomas (seven astrocytomas grade II-IV, three oligodendrogliomas, and one ependymoma) the numerical aberrations were gains of chromosomes 1 (once), 7 (twice), 10 (once), 11 (twice), and X (twice); losses of chromosomes 1 (once), 10 (twice), 17 (twice), and Y (once); and complete tetraploidy (once). Among the 18 investigated meningiomas monosomy 18 and trisomy 17 were observed once and twice, respectively. An additional hybridization with a cosmid probe for the BCR gene on 22q 11 indicated monosomy 22q in 11 meningiomas. These results show the value of interphase cytogenetics for the analysis of solid tumors for which it is relatively difficult to obtain sufficient metaphases of good quality for conventional cytogenetics.

An amyloid protein that precipitates in the cerebral vessel walls of Dutch patients with hereditary cerebral hemorrhage with amyloidosis is similar to the amyloid protein in vessel walls and senile plaques in brains of patients with Alzheimer's disease, Down syndrome, and sporadic cerebral amyloid angiopathy. Cloning and sequencing of the two exons that encode the amyloid protein from two patients with this amyloidosis revealed a cytosine-to-guanine transversion, a mutation that caused a single amino acid substitution (glutamine instead of glutamic acid) at position 22 of the amyloid protein. The mutation may account for the deposition of this amyloid protein in the cerebral vessel walls of these patients, leading to cerebral hemorrhages and premature death.

A 46-year-old man presented with Aspergillus fumigatus spondylodiscitis after lumbar surgery. He was successfully treated with the new antifungal drug itraconazole in combination with surgical debridement of the disc space. The patient has remained on itraconazole for more than a year and tolerated the drug well.

Cerebral hemorrhages with amyloidosis and dementia of the Alzheimer type have many neuropathological findings in common, but there are also marked quantitative and qualitative differences. That makes it highly improbably that the B-protein amyloid depositions itself are the direct cause of extensive neuronal death and dementia in DAT.

An alveolar soft part sarcoma localised in the pituitary gland extended into the suprasellar region. Three years after surgical removal there was a recurrency in the occipital horn of the right cerebral ventricle. This type of tumour predominantly occurs in the limbs and has never been reported in the pituitary region.

The case is described of a boy with some right ventricular dysplasia and episodes of ventricular tachycardia of left bundle branch block pattern who had symptoms from the age of 1 month. Angiography and cardiac biopsy demonstrated major involvement of the left ventricular myocardium. A sister of the patient presented at the age of 2 months with predominantly left ventricular cardiomyopathy; clinical signs and angiography suggested the presence of right ventricular dysplasia as well. She died suddenly at the age of 9 years. Her brother, now aged 14 years, is being treated with antiarrhythmic drugs. The hypothesis of this cardiomyopathy being a variant of "arrhythmogenic right ventricular dysplasia syndrome" is discussed.

✓ The authors present a retrospective analysis of the results of the cytological examinations of cerebrospinal fluid (CSF) samples and tumor-cyst aspirates deriving from 262 patients treated for malignant intracranial primary and secondary tumors, and vertebral and peridural metastastic processes. Positive preoperative CSF samples were found in 15.3% of all cases of primary cerebral malignancies (13.9% of all gliomas) and positive postoperative CSF samples were found in 40% (91% of the medulloblastoma cases). In all cases of single or multiple secondary cerebral tumors, positive preoperative CSF samples were found in 20%.

Choroid plexus papillomas in the posterior fossa can present with different clinical signs and symptoms. The tumors in the patients we discuss in this article originated from different sites of the choroid plexus. One patient, who had a fourth ventricle papilloma, experienced unsteady gait and episodes of dizziness over many years. The tumor was cystic an calcified, and adherent to the brain-stem. The second patient had only signs of increased intracranial pressure. A soft tumor was located in the cerebellomedullary cistern. The third patient, with a papilloma in the cerebellopontine angle, complained of hearing loss. This tumor was firmly adherent to the dura mater and looked exactly like a meningioma. The appearance on computed tomography scan, the macroscopic aspect, and the vascular supply of a papilloma in the posterior fossa can vary considerably.

• In two cases of varicella-associated cerebellar ataxia, varicella-zoster antigens in CSF cells were shown by an indirect immunofluorescent technique. Direct viral invasion in CNS disease complicating varicella plays an important part in pathogenesis and rules out a single immune-mediated mechanism.

✓ A case of a malignant neurofibroma of the cauda equina is described. Its location seems to be rare. An extensive surgical resection including the adjacent neural tissue and the enveloping dural sac was carried out, followed by radiotherapy.

• A persistent blink reflex to light (BRL) was observed in a patient who became comatose after a cardiac arrest. Postmortem examination revealed severe hypoxic ganglion cell necrosis of the cerebral and cerebellar cortex, the basal ganglia, the hypothalamus, nuclei in the brain stem, and the superior colliculi. The pretectum was unaffected. These findings suggest that the afferent fibers of the BRL enter the brain stem not in the superior colliculus, but in the pretectum.

Interphase nuclei isolated from paraffin-embedded tissue of four normal brains were hybridized with biotinated repetitive DNA probes specific for the (peri) centromeric regions of chromosomes 1 and 7. Hybridization results were visualized with a peroxidase-DAB system after which the number of specific signals per nucleus was counted using bright field microscopy. Using the probe specific for chromosome 7 (p7t1), both the cerebral and the cerebellar samples showed 2 spots in 82% and 83%, respectively, of the nuclei. In situ hybridization with the chromosome 1 probe (pUC1. 77) showed two spots in 69% of the cerebral nuclei. In cerebellar samples, hybridization with pUC1.77 resulted in only one large spot per nucleus in 82% of the cells. The average spot size in nuclei with one signal was about 1.6 times as large as that in nuclei with two signals. These observations suggest that the single large spot in the cerebellar cells is not the result of monosomy of chromosome 1 but that it reflects somatic pairing of the two chromosome 1 centromeres. Based on the size and the fraction of nuclei with one large spot, the small granular neuron is the most likely candidate. The difference between cerebral and cerebellar samples indicates that this somatic pairing of chromosome 1 is a cell-type-dependent phenomenon.

• A large family with hypokalemic periodic paralysis was reexamined after 50 years. Two new cases were found in the third generation and 12 in the fourth generation. This family now includes 28 affected patients in four generations. The reexamination ascertained the presence of permanent muscle weakness (PMW) in all investigated affected sibs. This fact, and the fact that indications of the presence of PMW without paralytic attacks were found in only one subject, is strong evidence that both are manifestations of the same more or less fully penetrant dominant gene. A linkage study in this family could not localize the gene on the human genome, but close linkage with 25 genetic marker systems could be excluded.

• We report an instance of progressive multifocal leukoencephalopathy in which cytarabine administration was successful as demonstrated by clinical course and follow-up computerized tomography studies. In this case, simian virus 40 (SV40) antigen was demonstrated in CSF cells by the indirect immunofluorescence technique.