Yanagi T

Neuron-specific enolase and S-100 protein levels in cerebrospinal fluid of patients with various neurological diseases.

Neuron-specific enolase (NSE) and S-100 protein (S-100) levels in cerebrospinal fluid (CSF) were determined in 129 patients with various neurological diseases. The chronological changes of these nervous system-specific proteins in CSF were also examined in 3 patients with acute disorders. NSE and S-100 levels were elevated in many cases with acute conditions. These specific proteins did not increase simultaneously but independently. These results suggested that NSE and S-100 in CSF would be useful markers for damage of the nervous system and that measurement of both NSE and S-100 might positively indicate whether the damage was neuronal, glial or mixed in origin. Moreover, from the serial determination of these substances, they would be better markers than cell counts and total protein in CSF for the active injury for the nervous tissues.

A radiological analysis of heart sympathetic functions with meta-[123I] iodobenzylguanidine in neurological patients with autonomic failure

Cardiac scintigraphy with meta-[123I]iodobenzylguanidine (MIBG) is used to assess cardiac sympathetic function. We performed [123I]MIBG scintigraphy in 7 patients with neurological diseases presenting orthostatic hypotension and other autonomic failures (AF), 22 neurological patients without AF, and 9 healthy subjects. Thallium scintigraphy and echocardiography were also performed in all subjects. In this series, patients with any evidence of cardiac dysfunction were excluded. No [123I]MIBG accumulation was observed in all patients with AF, and cardiac defects were noted in 7 patients (5 with Parkinsons disease [PD], 2 with spinocerebellar degenerations [SCD]), and in some patients without AF. In contrast, the distribution of [123I]MIBG was normal in all the healthy subjects. No decrease in [123I]MIBG accumulation was resulted from drug therapy (droxidopa, amezinium and thyrotropin-releasing hormone). In conclusion, reduced accumulation on [123I]MIBG scintigraphy may be due to myocardial beta-adrenoceptor dysfunction or reduced central sympathetic activity of the heart, or both.

Cervical spondylotic amyotrophy. Magnetic resonance imaging demonstration of intrinsic cord pathology.

Study Design. Three case reports. Objective. To elucidate the pathophysiology of cervical spondylotic amyotrophy. Summary of Background Data. Cervical spondylotic amyotrophy is the clinical syndrome in cervical spondylosis characterized by severe muscular atrophy in the upper extremities, with an absent or insignificant sensory deficit. Pathophysiology of this particular syndrome has not been well understood. Methods. Three cases of cervical spondylotic amyotrophy are presented in which magnetic resonance imaging confirmed the intrinsic cord disease as the cause of the syndrome. Results. The patients had segmental muscular atrophy of the proximal upper extremities, with an absent or insignificant sensory deficit. After initial disease progression, the symptoms stabilized for years. Sagittal T2‐weighted magnetic resonance images showed multisegmental linear high‐signal intensity within the compressed spinal cord. These high‐signal intensity lesions appeared to be located at the anterior horns on axial images. The spinal cord compression was less severe in the neck‐neutral position, but spinal canal stenosis increased when the neck was extended. Conclusions. The results suggest that one pathophysiology of this syndrome may be multisegmental damage to the anterior horns caused by dynamic cord compression, possibly through circulatory insufficiency.

Cerebrospinal fluid levels of superoxide dismutases in neurological diseases detected by sensitive enzyme immunoassays

We measured cerebrospinal fluid (CSF) levels of Cu/Zn superoxide dismutase (Cu/Zn SOD) and Mn superoxide dismutase (Mn SOD) using enzyme immunoassays in 196 neurological patients and 44 controls. The mean Cu/Zn SOD level was 55.8 +/- 27.6 (SD) ng/ml and the Mn SOD, 8.0 +/- 2.5 ng/ml in the controls. Cu/Zn SOD or Mn SOD levels showed neither age-nor sex-related differences in the controls. Both SODs were markedly elevated in cerebrovascular diseases, bacterial meningitis and encephalitis. Mn SOD alone was significantly elevated in neurodegenerative diseases. We compared SODs with CSF levels of neuron-specific enolase (NSE) and S-100b protein (S-100b) in cerebral infarction and bacterial meningitis. Both SODs were correlated with NSE and S-100b in patients with cerebral infarction, but not in those with bacterial meningitis. This means that elevations of SODs in CSF may not only be due to leakage from damaged nervous tissues, but also to the induction of SOD in lesions. We conclude that the mean SOD levels were elevated in various neurological diseases, and their varied magnitudes may be associated with the underlying diseases.

Differential response to corticosteroid therapy of MRI findings and clinical manifestations in spinal cord sarcoidosis

Abstract Spinal cord sarcoidosis is a rare disorder whose natural history and therapeutic outcome are not fully known. We examined four patients with spinal cord sarcoidosis both clinically and radiologically, particularly in relation to corticosteroid treatment. The initial manifestation was cervical myelopathy in three and uveitis in one. All four patients progressed slowly until corticosteroid therapy was initiated. The cervial spine was involved in all patients. Magnetic resonance imaging (MRI) showed spinal cord swelling with T2-weighted high intensity and linear leptomeningeal and patchy or diffuse intramedullary enhancement with gadolinium diethylene triaminepentaacetic acid. With corticosteroid therapy, dramatic improvement was seen on MRI, including disappearance or marked reduction of swelling and enhancement. Plasma levels of angiotensin-converting enzyme (ACE) were also markedly improved. In contrast, the clinical symptoms were little improved in one patient, unchanged in two, and rather worsened in one patient. Recurrence was seen on MRI at the maintenance dose in all four patients, without any dramatic change in clinical manifestation. MRI findings and plasma ACE are well correlated with active leasion of the spinal cord sarcoidosis, providing a useful marker for recurrence, but do not parallel the clinical manifestations.

Motor conduction studies in Miller Fisher syndrome with severe tetraparesis.

Some patients with Miller Fisher syndrome (MFS) have a severe tetraparesis such as that observed in Guillain–Barré syndrome (GBS). To determine whether pathophysiologic differences exist between the tetraparesis in MFS and that in GBS, we compared clinical and motor conduction findings in 4 MFS patients who developed severe tetraparesis with those in 5 MFS patients without tetraparesis, and 14 GBS patients. MFS patients with or without tetraplegia had normal motor conduction velocities, distal motor latencies, compound muscle action potential (CMAP) amplitudes, and F‐wave latencies. CMAP amplitude tended to be lower in tetraparetic MFS patients than in MFS patients without tetraparesis, but not significantly. F‐wave occurrence was slightly reduced in 1 MFS patient with tetraparesis and 1 MFS patient without tetraparesis. Motor conduction parameters were abnormal in 13 of 14 patients with GBS, and showed demyelinating features in 10. Our results suggest that the pathophysiology of tetraparesis in MFS differs from that in GBS.

Familial amyloidotic polyneuropathy with late-onset and well-preserved autonomic function: a Japanese kindred with novel mutant transthyretin (Ala97 to Gly).

We report the characteristics of one patient and two asymptomatic carriers from a Japanese family with familial amyloidotic polyneuropathy (FAP). The clinical features were somatic sensory and motor neuropathy with well-preserved autonomic function and late onset with slow insidious progression. These symptoms and signs are different from those of type 1 FAP. There were massive amyloid deposits with transthyretin (TTR) in the myocardium and the sural nerve. DNA sequencing of the TTR gene and amino acid sequence analysis of serum TTR revealed a new mutation in which Gly97 was substituted for Ala. We suggest that patients with somatic sensory and motor neuropathy of unknown origin without apparent autonomic dysfunction should be further studied for TTR mutation.

Clinico-pathophysiological features of acute autonomic and sensory neuropathy : a long-term follow-up study

We evaluated the clinicopathophysiological features of three patients with acute autonomic and sensory neuropathy (AASN) who were followed for over 3 years. Signs of an autonomic disturbance including vomiting, anhidrosis, urinary disturbances, orthostatic hypotension and reduced coefficient of variation of the R-R interval on electrocardiography gradually improved about 1 year after onset. However, all three exhibited severe generalized sensory impairment for all modalities with the development of persistent sensory ataxia. No sensory nerve action potentials could be elicited and no somatosensory evoked potentials could be obtained. Sural nerve biopsy revealed severe axonopathy. In two patients, a high-intensity area was observed in the posterior column of the spinal cord on T2*-weighted axial magnetic resonance images. The level of neuron-specific enolase in cerebrospinal fluid was markedly elevated in two patients, indicating spinal nerve root or sensory neuron damage. Motor nerve function was well preserved in all patients. Our findings suggests that the major lesion in patients with AASN, particularly those with a sensory deficit, is present in the dorsal root ganglion neurons, that is there is a ganglioneuronopathy.

Chronological changes of 123I-MIBG myocardial scintigraphy and clinical features of Parkinson's disease

Objectives The aim of this study was to investigate chronological changes of 123I-meta-iodobenzylguanidine (MIBG) myocardial scintigraphy and its relation to clinical features in patients with Parkinsons disease (PD), and to characterise patients with PD with normal or mildly low MIBG uptakes at their early stages. Methods The participants were 70 patients with PD who underwent 123I-MIBG myocardial scintigraphy twice or more. A cluster analysis was performed using parameters calculated from heart to mediastinum (H/M) ratio and washout ratio (WR). Results At baseline, the mean early H/M ratio (H/M(E)), delayed H/M ratio (H/M(D)) and WR were 1.83, 1.69 and 41.7%, respectively. After a mean interval of 3.0 years, follow-up studies showed significantly declined H/M(E) (1.69, p<0.001), declined H/M(D) (1.47, p<0.001) and enhanced WR (43.8%, p=0.007). Our longitudinal observations revealed that there existed heterogeneous changes in MIBG uptakes among patients. The cluster analysis classified the patients into two subgroups: 42 patients with markedly low MIBG uptakes at baseline (group A) and 28 patients with normal or mildly low MIBG uptakes at baseline (group B). Group B showed a significantly higher ratio of females, younger age at onset, lower Hoehn and Yahr stage and less demented, compared with group A. Conclusions Follow-up studies of MIBG divided the patients with PD into two major subgroups. A subgroup of patients with PD with normal or mildly low MIBG uptakes at the early stages of illness was characterised by female-dominant, young onset, slow progression in motor dysfunctions and preserved cognitive function. Trial registration number 1033.

Elevated cerebrospinal fluid levels of manganese superoxide dismutase in bacterial meningitis

We examined the mechanism of increase of manganese superoxide dismutase (Mn SOD) in the cerebrospinal fluid (CSF) in bacterial meningitis (BM). The elevated levels of Mn SOD in the CSF in BM, measured with an enzyme immunoassay method, were more prominent than those in aseptic meningitis (AM) and encephalitis (EN). In AM and EN Mn SOD levels well correlated with levels of neuron-specific enolase and S-100b protein, which are markers of damages to nervous tissues, but did not with any of them in BM. CSF concentrations of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 alpha (IL-1 alpha) were higher in BM than in AM and EN. From the serial measurements in BM, the peak values of these cytokines chronologically preceded or corresponded to those of Mn SOD. Immunohistochemically, a large number of the glial cells were stained for Mn SOD in the cerebral cortex from a patient with BM. By contrast, in the normal cerebral cortex, the glial cells were negative for Mn SOD staining. These results suggest that the marked increase of Mn SOD in the CSF in BM may be related to the increase of such cytokines as TNF-alpha and IL-1 alpha and that these cytokines may play a role in the induction of Mn SOD in nervous tissues.