Gianpaolo Pizzolato

TOXOPLASMA ENCEPHALITIS IN PATIENTS WITH THE ACQUIRED IMMUNODEFICIENCY SYNDROME

Among 504 cases of AIDS diagnosed between 1983 and 1990, there were 86 patients (17%) with toxoplasma encephalitis (TE). All were symptomatic at the time of diagnosis. General signs such as fever, neck stiffness, or headache were present in 87.2%, and 75.6% had focal signs. The primary means of diagnosis was computerized tomographic scanning, revealing 169 lesions of which 80% were immediately contrast-enhancing. All patients had IgG antibodies against Toxoplasma gondii either before (74 of 75 evaluable patients) or at the time of diagnosis of TE (73 of 75). Elevated antibody titers were present in 44% of evaluable patients, compared to 11% of patients with AIDS and other opportunistic infections. Initial treatment was pyrimethamine plus sulfonamides in 65 patients, and pyrimethamine plus clindamycin in 12 patients, with other combinations or no treatment accounting for the remainder. Life-table analysis of the time to discontinuation of treatment because of suspected side effects suggested that sulfadiazine was significantly more toxic, with 48% of patients experiencing an interruption in treatment after 30 days, than pyrimethamine (12%) or clindamycin (24%). The 30-day mortality rate was 12%, and median survival was 310 days after diagnosis, 530 in patients treated with zidovudine and 190 days in those not so treated. Of 82 evaluable patients, 16 relapsed once and 4 of these more than once. The risk of relapse was 27% 1 year after diagnosis of a first episode of TE.

Expression and localization of VEGF‐C and VEGFR‐3 in glioblastomas and haemangioblastomas

Primary human brain tumours account for approximately 2% of all cancers. High levels of expression of vascular endothelial growth factor‐A (VEGF‐A), a potent angiogenic factor, are linked to poor prognosis. In contrast, the potential role in human brain tumour biology of newer VEGF family members, VEGF‐C and VEGF‐D, both of which are lymphangiogenic factors, is poorly understood. In the present study, the expression of all VEGFs (VEGF‐A, ‐B, ‐C, and ‐D) and their receptors (VEGFR‐1, ‐2, and ‐3) has been assessed in 39 primary human brain tumours. The well‐established findings were confirmed with VEGF‐A. Surprisingly, however, VEGF‐C and VEGF‐D, as well as VEGFR‐3, were expressed in some tumour types such as haemangioblastomas and glioblastomas, despite their lack of lymphatic vessels. VEGF‐C and VEGFR‐3 transcripts were localized to the tumour palisade around necrotic areas in glioblastomas and were evenly distributed throughout haemangioblastomas. VEGF‐C protein was localized by immunohistochemistry to the palisade layer in glioblastomas. More than 50% of VEGF‐C‐positive cells also expressed the intermediate‐stage inflammatory macrophage marker CD163; however, a significant proportion of VEGF‐C‐positive cells were CD163‐negative. These data demonstrate the presence of molecules, primarily described as regulators of lymphangiogenesis, in normal human brain and brain tumours that are devoid of lymphatics. Their localization in macrophages points to a role in tumour‐associated inflammation. Copyright

Neuropathology of a case of dopa-responsive dystonia associated with a new genetic locus, DYT14

Detailed autopsy findings are reported for a patient with dopa-responsive dystonia genetically related to the dopa-responsive dystonia locus DYT14 on chromosome 14q13. Substantia nigra and locus ceruleus showed a normal abundance of severely hypomelanized dopaminergic neurons and no Lewy body. In the nigra, the reduction of melanin pigment was found to be asymmetric between the two sides and uneven within neurons, and the lateral aspect of the nigra appeared more affected than the medial, in a pattern similar to the neuronal loss in PD. Dopa-responsive dystonia has a unique neuropathologic signature that seems to be independent of its genotype.

Cerebral vasculitis during FK 506 treatment in a liver transplant patient

The immunosuppressive agent FK 506 is widely used in liver transplant patients. Neurotoxicity is a major complication of its use. We report progressive and irreversible neurologic complications occurring in a 39-year-old women who underwent liver transplantation and was treated with FK 506. Neuropathologic examination revealed multiple vasculitic lesions. The possibility of an FK 506-mediated toxic effect on the cerebral vessels is suggested.

Proximal myotonic myopathy: clinical, electrophysiological and pathological findings in a family.

Proximal myotonic myopathy (PROMM) is an autosomal dominant muscle disorder characterized by proximal weakness, myotonia, muscle pain and cataract. It resembles Steinert myotonic dystrophy (MD), but weakness is proximal, without facial muscle involvement, and the chromosome 19 CTG trinucleotide repeat expansion characteristic of MD is not present. We describe a further family with PROMM. Affected members complained of weakness of lower limbs or of myotonia. EMG revealed diffuse myotonic discharges. Muscle histology showed dystrophic abnormalities. The PROMM phenotype varies, even in the same pedigree, and may mimic MD or limb-girdle muscle dystrophy. EMG is particularly useful, since it may disclose myotonic discharges even in the absence of overt myotonia. Thus far it is not known whether PROMM is a single entity, or if it represents a heterogeneous group of disorders. This question will probably soon be settled through genetic analysis.

Fulminant Lewy body disease

The clinical distinction between Parkinsons disease (PD) with dementia (PDD) and dementia with Lewy bodies (DLB) is challenged by most neuropathological studies showing nearly identical changes in both conditions. We report an unusual case of PD evolving into a rapidly progressive dementia leading to death within 3 months that showed nearly all clinical features of DLB. At autopsy, numerous Lewy bodies and Lewy neurites were found in several areas of the brainstem, the limbic system, and the neocortex, consistent with pure DLB. This case demonstrates that Lewy body disease may exhibit a dramatic course without any coexisting pathology and exemplifies that PD, PDD, and DLB may sometimes represent sequential, yet overlapping, phenotypes of a same clinicopathological entity.

Well Differentiated Cerebellar Tissue within a Mature Cystic Teratoma

We describe the case of a 27 year-old woman presenting with acute abdominal pain due to torsion of a right ovarian cyst. Histopathological examination of the excised lesion revealed a mature cystic ovarian teratoma consisting primarily of a highly organized cerebellar component, an exceedingly rare finding. The possibility of a malignant neuroepithelial tumor arising from immature precursor cells within this neural tissue justifies complete excision of such lesions.

Mitochondrial anomalies in a Swiss family with autosomal dominant myoglobinuria

We report on a Swiss family in which 10 individuals of both sexes in 4 successive generations suffered from myoglobinuria, precipitated by febrile illness. It is the second family described with autosomal dominant inheritance of myoglobinuria. Four individuals suffered acute renal failure, which in two was reversible only after dialysis. In a recent case, a mitochondrial disorder was suspected because of an abnormal increase in lactate levels during an exercise test and because of a subsarcolemmal accumulation of mitochondria in a muscle biopsy, associated with a lack of cytochrome C oxidase in some muscle fibers. No mutation in the mitochondrial DNA was identified. Along with the inheritance pattern, these findings suggest that the myoglobinuria in this family is caused by a nuclear-encoded mutation affecting the respiratory chain.