Compound heterozygous genotype is associated with protracted juvenile neuronal ceroid lipofuscinosis.

We present a clinicopathological study and the first molecular genetic analysis of a family with 2 siblings affected by a rare, protracted form of juvenile neuronal ceroid lipofuscinosis (JNCL). Molecular genetic studies showed that both siblings, in addition to being heterozygous for the 1.02-kb CLN3 deletion, a common mutation in JNCL, also had a G-to-A missense mutation at nucleotide 1,020 of the CLN3 cDNA sequence on the non-1.02-kb deletion chromosomes. This point mutation resulted in a substitution of glutamic acid by lysine at position 295 of the CLN3 protein. Thus, a single point mutation at residue 295 of the CLN3 protein in protracted JNCL may underlie the phenotype in this form, which differs from that in classic JNCL.

Pelizaeus-Merzbacher-like disease: exclusion of the proteolipid protein locus and documentation of a new locus on Xq.

A large X-linked kindred with Pelizaeus-Merzbacher like disease (Pelizaeus-Merzbacher disease [PMD] lacking a proteolipid protein [PLP] mutation) was studied for linkage to 34 X-chromosome short tandem repeat polymorphism markers. Recombinational events excluded linkage to PLP and supported linkage to a 9.4-cM critical region more than 10 cM away from PLP on the X chromosome. A maximum 2-point lod score of 3.91 was observed for DXS441 at theta = 0.0. Neuropathologic study of one affected male showed intact myelin. The data thus support a different etiology for a disease that clinically resembles PMD, distinguishable phenotypically only by degree of myelin involvement. Other patients with the clinical diagnosis of PMD but without PLP mutations could have mutations at this new locus.

Meige syndrome in the spectrum of Lewy body disease.

We report a patient with Meige syndrome (segmental cranial dystonia) who had neuropathologic changes of Parkinson's disease on postmortem examination. Neuropathologic examination showed typical and atypical Lewy bodies in the pigmented nuclei of the brainstem (substantia nigra, locus ceruleus), the nucleus basalis of Meynert, and the nucleus ambiguus. Neurochemical analysis of postmortem brain tissue showed evidence for decreased dopamine turnover in the substantia nigra, striatum, and nucleus accumbens. We propose that some cases of Meige syndrome may be included in the spectrum of Lewy body disease.

Autosomal dominant parkinsonism with benign course and typical Lewy-body pathology.

The few previously reported patients with familial parkinsonism and Lewy-body pathology in the substantia nigra displayed a variety of clinical and pathologic syndromes. We now describe a family with very slowly progressive Parkinson's disease (PD) that has, in most cases, responded poorly to levodopa and includes subjective visual difficult. Four personally confirmed cases--with onset at ages 35, 25, 16, and 16-have occurred in three generations, and four suspicious cases have occurred in three other generations. There has been a trend toward progressively younger age of onset. One autopsied case showed a distribution of cell loss and Lewy bodies typical of PD. The hereditary pattern is most compatible with autosomal dominance. This kindred's illness shows that a presumably single Mendelian dominant gene can cause the clinical and pathologic features of PD, and further extends the clinical spectrum of pathologically typical Lewy-body PD.

Levodopa-nonresponsive Lewy body parkinsonism: clinicopathologic study of two cases.

We report two patients with a primarily akinetic form of parkinsonism who were nonresponsive to treatment with levodopa. At autopsy, both patients had many Lewy bodies in brainstem and diencephalic nuclei, with sparse Lewy bodies in association cortices and more numerous Lewy bodies in the limbic cortices, consistent with the transitional form of Lewy body disease. These cases emphasize that (1) Lewy body Parkinson's disease cannot be excluded on the basis of atypical presentation or levodopa nonresponsiveness, and (2) the clinicopathologic spectrum of Lewy body disease is varied.

Pink spots of Hedley-Whyte in formaldehyde-fixed brains. The subject revisited.

In an article published in 1985, Hedley-Whyte described "pink spots," which she observed in gross sections of human brains fixed in formaldehyde solution. Hedley-White found that the spots in question were associated with the presence of bacteria within central nervous system blood vessels. We have recently encountered three cases of Hedley-Whyte-type pink spots during routine postmortem brain examination. In two of these cases, the patient's clinical history included a bacterial infection, which could account for the deposition of bacteria within the central nervous system blood vessels. In the third case, the patient had no clinical history of bacterial infection, and had a negative postmortem blood culture. On microscopic examination, all three cases showed central nervous system intravascular presence of bacteria within the macroscopically recognized pink spots. To test the hypothesis that pink spots result from bacterial fermentation products, at the time of postmortem removal of brains (different from the brains mentioned above), we perfused blood vessels in three brains with 100% ethanol. Subsequent macroscopic examination after fixation in formaldehyde revealed discoloration similar to the Hedley-Whyte spots.

The possible role of substances inhibiting protein synthesis on the treatment of the spongiform encephalopathies.

The transmissible spongiform encephalopathies are probably caused by infectious proteinaceous agents called prions. It is suggested that these encephalopathies may be amenable to treatment by substances which inhibit protein synthesis.

Sudden, unexpected death due to fourth ventricular subependymoma.

A case of sudden, unexpected death due to fourth ventricular subependymoma (subependymal glomerate astrocytoma) in a 60-year-old man is presented. Sudden, unexpected death due to uncomplicated subependymoma has not been previously described.

Bronchopleural fistula in a neonate.

Bronchopleural fistula (BPF) produced by endotracheal suction catheter is a known cause of persistent pneumothorax in preterm infants in intensive care nurseries. This report describes the pulmonary pathology of a neonate who had sustained this injury. The observation suggests that the abnormal airflow results in severe damage of the involved lobe and an unusually mild bronchopulmonary dysplasia in the rest of the lung. This is in agreement with the fact that BPF acts as the path of least resistance for the oxygen-rich air from the ventilator.