Clinico-pathological comparative study between brainstem encephalitis of Iizuka type and neuro-Beh?et's disease

We experienced one necropsy case of brainstem encephalitis of Iizuka type (BSE) and one necropsy case of the brain-stem syndrome (BSS) of typical neuro-Beh?et's disease, and compared them clinically and neuropathologically. Clinically both of these cases showed chronic progressive mental disturbance, pseudobulbar paresis, spastic tetraparesis, cerebrospinal fluid pleocytosis, increased protein, and brainstem atrophy observed by X-CT. Neuropathologically, irregular, boundary-indistinct demyelinating lesions and obsolete softening lesions were sporadically found, associated with perivascular lymphocytic infiltration and gliosis centering on the brainstem. In this way, both cases were similar in many points except for the presence or absence of cutaneo-muco-ocular signs specific for Beh?et's disease. Also BSE and BSS reports in the literature showed that both diseases were similar not only in clinical findings consisting of mental disturbance and brainstem signs but also in neuropathological findings with similar topographical distribution of the same histopathological changes, including the variations and diversity of these characteristics. Especially of much interest is their similarity in characteristic mental disturbance. In discriminating BSE from multiple sclerosis and other diseases with exclusive involvement of the brainstem, it is important to understand their clinical characteristics. The characteristic mental disturbance includes damage to memory and sentiment, a change in personality, and lowering in spontaneity, but calculation ability and orientation are comparatively preserved. Of course the similarity in clinical and neuropathological findings does not necessarily mean the identical etiopathogenesis. However, it is possible to consider that neuro-Beh?et's disease (syndrome) may form a wide spectrum with BSE and typical neuro-Beh?et's disease at the both ends, regarding the time and spatial diversity of the appearance of cutaneo-muco-ocular signs.     

Ultrastructural study of the motor end-plate in botulism and Lambert-Eaton myasthenic syndrome

The motor end-plate fine structure was studied in 3 patients with type A botulism and compared with that in 4 patients with Lambert-Eaton myasthenic syndrome (LES). In the botulism cases a biopsy of the biceps brachii muscle was performed at the chronic stage. The skeletal muscle showed a neurogenic change. The nerve terminal area had decreased and the postsynaptic regions had been denuded of their nerve terminals in 16% of the regions (9.8% in control). No highly simplified postsynaptic regions were observed. The findings are consistent with those observed at the motor end-plates in motoneuron diseases. By contrast, in LES no changes were observed in the presynaptic region. In the postsynaptic region, the postsynaptic membrane length and membrane density decreased and hypertrophy of the junctional folds was not observed.     

Serial diffusion-weighted MRI (DWI) in a patient with sporadic Creuztfeldt-Jakob disease]

Serial DWIs were performed in a patient with CJD who developed symptoms acutely and progressed rapidly. DWI discloed an increased signal in the frontal and parietal inner cortical areas, and in the caudate nuclei and putamina 20 days after the onset of symptoms. T2-weighted images showed only signal abnormality in the caudate nuclei and putamina, but not in the cerebral cortex. In the CSF obtained 15 days after the onset of symptoms, total tau protein was markedly elevated and 14-3-3 protein was positive. Measurement of these proteins are highly specific and sensitive for the diagnosis of CJD, but not available as a rapid routine examination at present. DWI is not specific, but useful for making the diagnosis of CJD in the early stage of the disease.     

A case of multiple sclerosis associated with myelin associated glycoprotein neuropathy]

A 28-year-old woman had developed chronic, recurrent, visual disturbance (bilateral), and girdle sensation at Th 5-6. She was admitted to our hospital because of left visual disturbance, distal limb weakness on right side, and numbness of four extremities. The neurological examination revealed decreased visual acuity of the left eye with abnormality of the optic disk, moderate muscle weakness of the right upper and lower extremities, absent tendon reflexes and paresthesia on distal portions of the four limbs. Laboratory examinations disclosed the titration of anti-myelin associated glycoprotein (MAG) antibody (IgM) and CSF protein was elevated (104 mg/dl). Motor nerve conduction studies revealed conduction block in more than one nerve. The conduction velocities in the upper and lower extremities were all diminished. P100 latency was prolonged by flash visual evoked potential (VEP) studies. N13-N20 interpeak latency of somatosensory evoked potential (SEP) of median nerve was also prolonged. She was treated with steroid pulse therapy, followed by an oral dose of 30 mg/day of prednisolone. Her symptoms resolved completely three months later, and multifocal conduction block subsided on electrophysiological study. There are some cases of multiple sclerosis with multifocal conduction block, but such a case is very rare in Japan. We discussed the pathogenic mechanisms of these conditions, and we conclude that we must take notice of demyelinating neuropathy in multiple sclerosis and that nerve conduction studies are useful for detecting them.     

High incidence of Haemophilus influenzae in nasopharyngeal secretions and middle ear effusions as detected by PCR.

PCR was used to detect Haemophilus influenzae in samples of nasopharyngeal secretion and middle ear effusion (MEE). Nasopharyngeal secretions were collected from 102 patients with otitis media with effusion and from 111 healthy subjects. Eighty samples of MEE were collected from patients with otitis media with effusion. A pair of primers was designed to amplify a DNA segment of the gene encoding P6 outer membrane protein of H. influenzae. The amplified PCR product was detected with an internal probe that hybridized specifically to the P6 DNA of H. influenzae. Samples of MEE and nasopharyngeal secretion were also examined by a conventional culture method. The incidence of P6 gene DNA in nasopharyngeal secretions detected by PCR was about two times higher than that of H. influenzae detected by the conventional culture. Culture-positive samples were all positive in the PCR test. In MEEs, the rate of detection of the P6 gene DNA target was about five times higher than that of H. influenzae detected by the culture method. All patients who had P6 gene DNA in MEEs were found to have the DNA in nasopharyngeal secretions. These findings suggest that the presence of H. influenzae in MEEs and in nasopharyngeal secretions is more common than previously reported.     

Epstein-Barr virus-associated post-transplant primary smooth muscle tumor of the liver: Report of an autopsy case

Epstein-Barr (EB) virus-associated primary smooth muscle tumors have been reported in immunosuppressed young patients with acquired immunodeficiency syndrome (AIDS) and young people who have undergone liver transplantation. An autopsy case of EB virus-associated smooth muscle cell tumor in a 21 year old female who received immunosuppres-sive therapy following renal transplantation Is repotted. Multiple tumor nodules were present in the liver, but no primary lesion was found in any other organ. Histologically, the nodules were composed of spindle cells, positive for α-smooth muscle action, which were arranged in fascicles and closely associated with vascular channels, thereby suggesting a vascular smooth muscle cell origin. EB virus infection of the tumor cells was clearly demonstrated by in situ hybridization with an EB virus-encoded RNA 1 (EBER-1) probe. The present case illustrates that EB virus infection may play some role in the development of smooth muscle tumors not only in immunocompromised young patients with liver allo-grafts, but also in those with renal allografts.     

Elevated levels of interleukin-12 and interferon-gamma in patients with human T lymphotropic virus type I-associated myelopathy

The levels of interleukin-12 (IL-12) (p70 heterodimer), total IL-12 (p70 heterodimer plus p40 chains), interferon-gamma (IFN-gamma) as Th1 cytokine, and those of interleukin-4 (IL-4) and interleukin-10 (IL-10) as Th2 cytokines in sera and cerebrospinal fluid (CSF) from 22 patients with human T lymphotropic virus type I (HTLV-I)-associated myelopathy (HAM) were compared with those of 22 patients with other neurological diseases (OND), including nine anti-HTLV-I-seropositive carriers. Both serum IL-12 (total and p70 heterodimer) and CSF IFN-gamma, measured by the enzyme-linked immunosorbent assay (ELISA), were significantly elevated in patients with HAM as compared to the patients with OND, including the anti-HTLV-I-seropositive carriers. Serum IFN-gamma also was significantly elevated in the HAM patients as compared to the controls. There was no significant difference in the CSF levels of IL-12 (total and p70 heterodimer) between the HAM patients and controls, whereas, for the Th2 cytokines IL-4 was detected in the CSF of four anti-HTLV-I-seropositive carriers of the 13 control patients but not in any of the patients with HAM. No significant difference was found in the serum levels of IL-4 and IL-10, nor in the CSF levels of IL-10 in the patients with HAM and in the controls. These findings indicate that in patients with HAM, the immunological balance of helper T lymphocytes between Th1 and Th2 is toward Th1 in the periphery and that Th1-mediated immunological status in the central nervous system is involved in the pathogenesis of HAM.     

Myonephropathic-metabolic syndrome as a complication of cardiopulmonary bypass

We encountered eight rare cases of myonephropathic metabolic syndrome (MNMS) which developed as a complication of the femoral arterial cannulation (FAC) during cardiopulmonary bypass (CPB). Seven were boys ranging in age from 4–17 years, and all had undergone open heart surgery using CPB with a hemodilution technique. These eight corresponded to 1.9 per cent of the 420 patients treated with CPB before June, 1974. The pump priming fluid used was either Ringer’s lactate solution alone or that containing a small amount of colloidal solution. Duration of CPB ranged from 52 min to 2 hrs and 42 min, but the FAC period was more than 3 hrs in each case. Acute renal failure occurred in 3 and 2 required peritoneal dialysis. Severe respiratory insufficiency occurred in 2 and one died 3 months after the operation. The most effective means to prevent the development of MNMS seems to be the local cooling of the cannulated limb during FAC. MNMS did not occur in 444 cases of CPB with FAC after July 1974, and here local cooling was applied in all cases.     

Role of expression of focal adhesion kinase in progression of hepatocellular carcinoma.

PURPOSE: Although hepatocellular carcinoma (HCC) is the most common cancer of the human liver, the mechanisms that regulate HCC development and progression remain unclear. The aim of this study was to investigate whether focal adhesion kinase (FAK) is involved in the progression of human HCC. EXPERIMENTAL DESIGN: Western blot analysis for FAK was performed on three HCC cell lines. We reviewed 64 consecutive patients who had undergone initial liver resection for HCC without preoperative treatment. Immunohistochemistry analysis for FAK was performed on paraffin-embedded tissues. FAK expression was confirmed by Western blot analysis in several clinical samples. We investigated the correlation between FAK expression and clinical outcome. RESULTS: FAK proteins were detected in all HCC cell lines. Hepatocytes in the normal liver and chronic hepatitis with or without cirrhosis were negative for immunohistochemical staining for FAK expression. Cytoplasmic FAK expression was observed in 18 of 64 patients (28.1%), and this positive staining was correlated with gender (P < 0.05), a lower level of serum albumin (P < 0.05), and portal venous invasion (P < 0.01). Positive staining for FAK was associated with significantly poorer survival (P < 0.05). In multivariate analysis, FAK overexpression was an independent factor in determining the prognosis of patients. CONCLUSIONS: These data suggest that FAK plays an important role in promoting tumor progression, especially vascular invasion, in HCC. FAK could play an important role in HCC progression and would be a novel target for HCC therapeutics as well as a prognostic marker.