Early clinical signs and imaging findings in Gerstmann-Sträussler-Scheinker syndrome (Pro102Leu).

OBJECTIVE: To determine the clinical and radiologic features of Gerstmann-Sträussler-Scheinker syndrome caused by Pro102Leu mutation in PRNP (GSS102). METHODS: The authors report 11 patients (nine families) with clinically and radiologically diagnosed GSS102. RESULTS: All patients showed mild gait disturbance, dysesthesia and hyporeflexia of the lower legs, and truncal ataxia, and 9 of 11 patients showed proximal leg muscle weakness during the early stage of the disease. Dementia was not a main symptom during the early stage. Brain MRI and EEG abnormalities were not prominent initially. SPECT (N-isopropyl-p-[(123)I]iodoamphetamine) analyzed by the three-dimensional stereotactic surface projection (SSP) method detected abnormalities in five patients early during the course of the illness. SPECT findings showed diffusely decreased cerebral blood flow, demonstrated by a mosaic pattern, with the lowest perfusion noted in the occipital lobes. In contrast, blood flow to the cerebellum was preserved. These studies suggested sites of pathology in GSS102, with the main lesions probably located in the cerebrum and the spinal cord (posterior horn and spinocerebellar tract) instead of the cerebellum. CONCLUSIONS: Key features for early diagnosis of Gerstmann-Sträussler-Scheinker syndrome caused by Pro102Leu mutation in PRNP (GSS102) are truncal ataxia, dysesthesia and hyporeflexia of the lower legs, and mild dysarthria. Normal cerebellar MRI and abnormal cerebral SPECT findings are characters of early GSS102.

Oral parafunctions and association with symptoms of temporomandibular disorders in Japanese university students.

We examined whether oral parafunctions are associated with symptoms of temporomandibular disorders (TMD) in 3557 Japanese university students, aged between 18 and 26 years. Participants completed a questionnaire regarding various oral parafunctions and subjective symptoms related to TMD, and underwent a dental examination. The prevalence of temporomandibular joint (TMJ) noise, TMJ pain and impaired mouth opening was 41.7, 16.0 and 16.3%, respectively. The most prevalent parafunction was sleeping on one side (60.2%), followed by supporting the jaw by leaning on the palm of the hand (44.8%). Mean age, decayed, missing and filled teeth, and number of teeth were not significantly different between TMD positive and negative groups according to unpaired t-test. The chi-squared test revealed that the ratio of females was significantly higher among students with TMD than without TMD. Multiple logistic regression models adjusted for age and gender demonstrated that chewing on one side caused an increased risk of TMJ noise [odds ratio (OR) = 1.52, P < 0.001], TMJ pain (OR = 1.54, P < 0.001), and impaired mouth opening (OR = 2.00, P < 0.001). Tooth clenching also increased the risk of TMJ noise (OR = 1.86, P < 0.001), TMJ pain (OR = 1.79, P = 0.001) and impaired mouth opening (OR = 1.88, P < 0.001). Further prospective cohort studies, including other potential risk factors, are required to clarify these relationships.

Usefulness of transcutaneous Doppler jugular venous echo to predict pulmonary hypertension in COPD patients.

Pulmonary hypertension is an important factor that determines the prognosis of chronic obstructive pulmonary disease (COPD) patients. Echocardiography is a noninvasive and useful bedside method for measurement of pulmonary artery pressure. However, this method is sometimes difficult because of the overinflated lungs in COPD patients. This study attempted to estimate pulmonary hypertension in COPD patients using transcutaneous Doppler jugular vein flow velocity recording. The mean pulmonary artery pressure (MPAP) of 64 COPD patients was examined using cardiac catheterization. The right jugular vein flow velocity was measured within 24 h using transcutaneous Doppler echo, after which the ratio of diastolic flow (Df) and systemic flow (Sf) velocity was calculated. Subsequently, the statistical correlation of MPAP and the Df/Sf ratio was examined. MPAP was also measured using standard cardiac echo methods and the results were compared. The Df/Sf velocity ratio showed significant correlation with MPAP in COPD patients (r=0.844, p<0.0001). The sensitivity was 71.4%, and the specificity 95.3% (cut-off ratio= 1.0). Jugular venous Doppler echo could be performed in all patients while other cardiac echo methods could not be performed in all patients. The specificity of the methods used was higher than other cardiac echo methods. Transcutaneous jugular vein flow velocity measurement may be applicable to bedside prediction of pulmonary hypertension in chronic obstructive pulmonary disease patients.

Familial skeletal myopathy with atrioventricular block.

OBJECTIVE: We studied familial cases of skeletal myopathy with atrial fibrillation (Af) and atrioventricular (AV) block to compare the clinical features to other myopathies associated with cardiac abnormalities. METHODS: Neurologic, cardiologic, electrophysiologic, muscle pathology, and genetic studies were performed on the patients showing muscle weakness. PATIENTS: Four patients (a 63-year-old mother, 30 and 32-year-old sisters, and their maternal grandmother) and three healthy family members from three generations were studied. The mode of inheritance was suspected as autosomal dominant. RESULTS: Two sisters with congenital myopathy without rigid spine developed Af and AV block at the age of 28 and 18, respectively. The mother showed AV block, and underwent pacemaker implantation at the age of 63. The maternal grandmother had dilated cardiomyopathy, Af and severe lordosis. She died of stroke attacks and congestive heart failure at the age of 78. Muscle biopsy obtained from the mother and sisters showed myopathic changes without characteristic abnormalities. No mitochondrial DNA mutations were found. Other inherited myopathies with cardiac complications were not suspected in this family. CONCLUSION: This Japanese family appears to belong to a new genetically heterogeneous group of autosomal dominant skeletal myopathy with severe AV block and Af.

Polarized transport was observed not in hydrophilic compounds but in dextran in Caco-2 cell monolayers.

We examined the efflux from the basal to apical side of fluorescein isothiocyanate-labeled dextran 4000 (FD-4) in Caco-2 cell monolayers using a diffusion chamber system. The permeation clearance (Pm) of FD-4 from the basal to apical side was 6 times greater than that from the apical to basal side at 37 degrees C. Such polarized efflux of FD-4 was evident at 37 degrees C, but not at 4 degrees C. Efflux of FD-4 was dose-dependently inhibited by colchicine, an endocytosis inhibitor. Adding an excess of unlabeled dextran (M.W. 10,000 Da) decreased the efflux of FD-4. On the other hand, transepithelial electrical resistance (TEER) did not change during the experiments under any conditions. These results suggest that the efflux of FD-4 across Caco-2 cell monolayers is apparently mediated by at least two polarized, energy requiring transport systems, one of which shows substrate specificity for dextran polysaccharides.

Characteristic expression of cell adhesion molecules in adhalin deficiency.

We have reported the reduction of the B1 subunit of laminin and that of heparan sulfate proteoglycan (HSPG) in two Japanese patients with adhalin deficiency. We here investigated immunohistochemically the expression of cell adhesion molecules, including intercellular adhesion molecule-1 (ICAM-1), neural cell adhesion molecule (NCAM), and CD44 (HCAM), in four Japanese patients with adhalin deficiency, compared to other types of muscular dystrophy. We found that NCAM was upregulated in a fair number of muscle fibers, regardless of the type of muscular dystrophy. ICAM-1 was detected on the rare muscle cell membrane in all patients. CD44 was barely detected on the muscle cell membrane in adhalin deficiency, in contrast to the strong expression of CD44 which was observed in other types of muscular dystrophy. These findings suggest that a different degenerative or regenerative process is involved in adhalin deficiency compared to other types of muscular dystrophy.

Familial facioscapulohumeral muscular dystrophy: phenotypic diversity and genetic abnormality.

We report two cases showing facioscapulohumeral muscular dystrophy (FSHD) with phenotypic diversity but the same genetic abnormality detected by a p13E-11 probe. The proband, a 26-year-old woman, showed an early onset, tortuosity of retinal arterioles and respiratory failure. The 53-year-old mother of the proband had limb-girdle (L-G) type muscular weakness with very mild facial involvement. Muscle biopsy showed perivascular cell infiltration in both patients. These cases suggest that the phenotypic diversity ranges from L-G type weakness to severe respiratory failure in FSHD family.

Type II muscle fibers are stained by anti-Fas antibody.

To examine whether apoptosis related proteins are present in skeletal muscles we studied biopsied muscles immunohistochemically and by Western blot analysis. Biopsied muscles from patients with several disorders were studied with anti-Fas antibody and anti-BCL2 antibody. Type II muscle fibers identified by ATPase staining were positively stained by anti-Fas antibody in both normal control and diseased muscles. Anti-BCL2 antibody did not stain any muscle fibers. Western blot analysis using anti-Fas antibody showed a single band at 45 kDa in both skeletal muscle and lymphocytes. Anti-Fas antibody has been reported to induce apoptosis in the cells. The presence of anti-Fas antibody reactive materials in type II muscle fibers might be related to type II fiber atrophy in muscular disorders.

Detection of HTLV-I provirus by in situ polymerase chain reaction in mononuclear inflammatory cells in skeletal muscle of viral carriers with polymyositis.

We tested for HTLV-I proviral DNA in skeletal muscle from patients with polymyositis infected with HTLV-I using the in situ polymerase chain reaction. We found the HTLV-I provirus in some of the CD4-positive cells in HTLV-I-positive polymyositis cases but not in HTLV-I-negative polymyositis ones. We could not detect HTLV-I within the muscle fibers. We suggest that HTLV-I-associated polymyositis is not due to direct, persistent infection of the muscle fiber by the virus, but to a T-cell-mediated immunological process triggered by the HTLV-I-infected cells.