Amyloid beta protein in plasma from patients with sporadic Alzheimer's disease.

Fibrillar amyloid beta protein (A beta) deposition is increased in the brains of patients with Alzheimer's disease (AD), and is manifested as senile plaques (SPs) and congophilic angiopathy (CA). A beta 40 and A beta 42(43), two chief species of A beta, are documented in SPs and CA, as well as in cerebrospinal fluid (CSF) and cell culture media. A beta 42(43) is the major component of diffuse plaques, the earliest form of SPs. Thus, we hypothesized that determination of the amount of A beta 42(43) in CSF or plasma might provide a diagnostic laboratory test for AD. We measured amounts of different A beta species in plasma from 28 patients with sporadic probable AD, 40 age-matched neurologic patients without dementia and 25 age-matched normal controls using enzyme-linked immunosorbent assays (ELISAs). Plasma concentrations of A beta 1-40 and A beta 1-42(43) did not significantly differ among these groups. These findings suggest the unlikelihood that plasma A beta assays would be useful as a diagnostic tool for AD.

Sural nerve biopsy in vasculitic neuropathies: morphometric analysis of the caliber of involved vessels.

We performed histologic and morphometric analyses of the sural nerve in 13 patients with vasculitic neuropathies. The ratio of vessels with vasculitis, the caliber of involved vessels, and pathologic changes of myelinated fibers were evaluated. In patients with polyarteritis nodosa (PN), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE), marked vasculitis with inflammatory cell infiltration and occlusion were observed in epineurial arteries greater than 100 microns in diameter, and mild vasculitic changes were noted in arterioles 40 to 100 microns in diameter. In vessels less than 40 microns, mild vasculitis with perivascular cuffing was noted in patients with RA and SLE, but not in PN. In a patient with microscopic PN, mild inflammatory cell infiltration was encountered around small vessels at diameters less than 40 microns as well as those greater than 100 microns. In a patient with nonsystemic vasculitic neuropathy, vasculitic changes were identified only in vessels less than 40 microns. In patients with Churg-Strauss syndrome (CSS), there were no distinct findings of vasculitis in any biopsy material. In conclusion, morphometric analyses of the caliber of involved vessels may be useful in the differential diagnosis and classification of underlying vasculitic neuropathies.

Prion disease with 144 base pair insertion in a Japanese family line.

We describe an insert mutation in the prion protein (PrP) gene in a Japanese family line that encodes six octapeptide repeats. This is the second report to date of an inherited prion disease with a 144-base pair insertion, although the order of the repeat sequences differ from that reported for the disease in an English family line. The clinical features, like those of the English patients, were characterized by a slowly progressive generalized dementia with some neurological signs and cortical focal symptoms. Postmortem examination disclosed diffuse atrophy of cerebral gray matter and the cerebellar cortex; histologically, there were marked patchy and regional neuronal loss with astrocytosis in the frontal cortex, amygdala and hippocampus and PrP-immunoreactive plaques in the molecular layer of the cerebellum. These plaques were different from typical kuru plaques. The prion disease in the present Japanese family line is compared with that in the English family line.

Dose-dependent association of apolipoprotein E allele epsilon 4 with late-onset, sporadic Alzheimer's disease.

We examined the apolipoprotein E (apo E) genotypes in 47 patients with late-onset sporadic Alzheimer's disease (mean age at onset +/- standard deviation, 72.2 +/- 6.4 years), 8 with late-onset familial Alzheimer's disease (75.5 +/- 5.1 years), 18 with early-onset sporadic Alzheimer's disease (52.8 +/- 4.7 years), and 10 with early-onset familial Alzheimer's disease (52.0 +/- 6.8 years) in Japan and compared them with genotypes in control subjects. In late-onset sporadic Alzheimer's disease, apo E-epsilon 4 frequency increased significantly (epsilon 4 frequency: 0.34 vs 0.095 in controls, p < 0.0001), and the odds ratio, which represents the strength of association between Alzheimer's disease and apo E-epsilon 4, markedly increased with increasing dose of apo E-epsilon 4 gene (3 [95% confidence interval, 2-6] in one dose; 43 [95% confidence interval, 12-154] in two doses). This study also suggested that apo E-epsilon 4 is associated with both late-onset (epsilon 4: 0.31) and early-onset familial Alzheimer's disease (epsilon 4: 0.35). In contrast, we found no association between apo E-epsilon 4 and early-onset sporadic Alzheimer's disease (epsilon 4: 0.08). These results indicate that the risk of developing late-onset sporadic Alzheimer's disease is markedly dependent on the dose of apo E-epsilon 4, while apo E-epsilon 4 does not appear to be a major risk factor for early-onset sporadic Alzheimer's disease.

Clinical evaluation of plasma exchange and high dose intravenous immunoglobulin in a patient with Isaacs' syndrome.

The clinical effects of plasma exchange and high dose intravenous immunoglobulin (IVIg) were evaluated in a 41 year old woman with Isaacs' syndrome. After double filtration plasma exchange, symptoms almost disappeared for two to three weeks and the recorded continuous muscle action potentials were considerably decreased. Symptoms recurred within a few months. On the other hand, IVIg worsened the symptoms of the disorder: during and after IVIg at a dose of 0.2 g/kg/day (total 50 g), widespread myokymia, pseudomyotonia, and muscle cramps gradually increased. Symptoms improved after another course of plasma exchange.

[A case of nonsystemic vasculitic neuropathy with anti-neutrophil cytoplasm antibody (ANCA)].

A 26-year-old woman with mononeuropathy multiplex complained of severe pain of right foot and ipsilateral steppage gait. Careful examination failed detect evidence of systemic lesions. Sural nerve biopsy revealed myelin ovoids and loss of myelinated fibers, which were different in severity among the fascicles. There were mild mononuclear cell infiltrations around arterioles in the epineurium. A diagnosis of nonsystemic vasculitic neuropathy (NSN) was made. Anti-neutrophil cytoplasm antibody (ANCA), a specific marker for microscopic polyarteritis nodosa and Wegener's granulomatosis, was positive in the patient. Oral administration of prednisolone ameliorated the sensorimotor disturbances, and ANCA turned to be negative. This is the first report of a patient with NSN showing positive ANCA.

[A case of microscopic polyarteritis nodosa accompanied by peripheral neuropathy].

We reported a 64-year-old woman with subacute sensorimotor polyneuropathy accompanied by marked inflammatory reactions and rapidly progressive glomerulonephritis. Polyneuropathy was followed in 3 months by a rapidly progressive renal dysfunction. Sural nerve biopsy revealed marked loss of myelinated fibers and myelin ovoid formation with vasculitis of the small-sized arteries and arterioles. Renal biopsy showed segmental necrotizing glomerulitis. These pathological findings were distinct from those of polyarteritis nodosa and led to a diagnosis of microscopic polyarteritis nodosa (MPN). Oral administration of prednisolone with an additional immunosuppressant was effective not only in alleviating the polyneuropathy, but also in preventing the deterioration of renal function. This is the first report that clearly describes the peripheral neuropathy in MPN.

[Syndrome of contracture facio-brachio-abdomino-crurale en flexion in a case of isolated ACTH deficiency--biopsy findings of muscle and nerve].

A 55-year-old woman presented with a one-year history of painful muscle cramps and progressive flexion contractures of the arms, pelvic girdles and knees. Laboratory evaluation was summarized as follows: low plasma cortisol and ACTH levels, delayed response of plasma cortisol to ACTH administration, no response of plasma ACTH level to insulin administration, and normal plasma LH, FSH, GH, TSH and PRL levels. She was diagnosed as isolated ACTH deficiency. EMG was silent in contractured muscles at rest. Biopsy of the biceps femoris muscle revealed a marked reduction in fiber size, type 2 fiber atrophy and type 1 fiber predominance. The nerve conduction velocities of the peripheral nerves were found to be decreased. The biopsied specimen of the sural nerve revealed a loss of large myelinated fibers and segmental demyelination. Both flexion contractures and nerve conduction velocities were gradually improved with the replacement of hydrocortisone.

[A case of progressive systemic sclerosis with Sjögren's syndrome presenting with coma, convulsion and bilateral thalamic hypodensity on computed tomography].

A 35-year-old female with progressive systemic sclerosis (PSS) and Sjögren's syndrome developed consciousness disturbance and generalized seizure after the episode of fever and erythema lasting for 3 weeks. Neurological examination disclosed deep coma and spastic tetraplegia with pathological reflexes. Laboratory data showed mild anemia, severe hypoproteinemia, hypoalbuminemia and increase of protein content in the cerebrospinal fluid. Cranial CT scans obtained after convulsion revealed diffuse brain swelling and bilateral symmetrical hypodensity involving the thalami and posterior limbs of the internal capsule. High-dose corticosteroid therapy and osmotherapy with correction of hypovolemia were started, because severe dehydration, hypoalbuminemia and cerebral vasculitis were suspected to change the vascular permeabilities. Neurological symptoms and CT findings were rapidly improved. Cerebral angiography 4 weeks after convulsion showed definite angitis. The patient was discharged 9 weeks after convulsion. In our case, a possible cause of the characteristic CT findings may be the disturbance of cerebral venous return due to hypovolemia and vasculitis. High-dose corticosteroid therapy may be recommended in patients with collagen disease, who show the bilateral symmetrical thalamic hypodensity on CT scans.

Spatial patterns of reflex evoked by pressure stimulation of the foot pads in cats.

1. The spatial patterns of reflexes elicited by localized pressure stimulation of the foot skin were analysed by recording electromyographic activities of various hindlimb muscles or muscle nerve discharges in cats anaesthetized with sodium pentobarbitone. 2. Reflex discharges evoked by stimulation of the central pad occurred mainly in physiological toe extensors located in the foot. Stimulus-response relationships of single motor units revealed characteristically wide ranges of graded response and recruitment. 3. Within the central pad, the strongest excitation was evoked from the central lobe and was distributed to extensors of all four toes. Excitation from the medial and the lateral lobes was usually asymmetrical and weaker in toe muscles of the stimulated side. It is suggested that the weakness was in part due to concomitant inhibition. 4. Stimulation of a toe pad caused marked suppression of central pad-evoked activity of toe extensors with a highly specific spatial pattern. The inhibition was strongest in extensors of its own toe, and gradually weaker in the more distant toes. Weak excitation was occasionally evoked in extensors of the most medial or lateral toes, when the most lateral or the most medial toe-pad, respectively, was stimulated. 5. A similar pattern of relfex to that from the toe pad was evoked from the claw base and the hairy toe dorsum of each digit. 6. Reflex effects, both inhibitory and excitatory, from the central and toe pads, claw bases and toe dorsum were maintained during prolonged stimuli, indicating that slowly adapting receptors contributed to these reflexes. 7. It is concluded that stimulation of localized skin areas of the foot, particularly the pads, evokes highly specialized reflexes, which may be important in controlling movements of individual digits.