The physiology of orthostatic tremor.

This article describes the physiological findings in a patient with orthostatic tremor. The tremor primarily affected the legs, was alternating between antagonist muscle groups, and had a remarkably rapid frequency of 16 Hz. It was present only during certain postures and appeared to be of central origin. A tremor of the same frequency was also recorded in the arms during particular movements, but was cocontracting. We suggest that orthostatic tremor may be generated by spontaneous oscillation in those central structures responsible for organizing the motor programs for standing.

CAG repeat number correlates with the rate of brainstem and cerebellar atrophy in Machado-Joseph disease.

We compared the CAG repeat length and the severity of the brainstem and cerebellar atrophy visualized by MRI in 30 patients with Machado-Joseph disease. We found a strong correlation between the CAG repeat number and the quotient of the degree of atrophy divided by age at examination. These results suggest that the rate of disease progression is dependent on the CAG repeat size and disease progression may commence at birth.

Effect of L-threo-3,4-dihydroxyphenylserine on muscle sympathetic nerve activities in Shy-Drager syndrome.

We observed changes in postganglionic efferent discharges of muscle sympathetic nerve (muscle sympathetic activity, MSA) microneurographically before and after the oral administration of L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS), a precursor of norepinephrine, in a patient with Shy-Drager syndrome and irregular fluctuations of blood pressure. Before drug administration, MSA was only rarely observed with the patient in the supine position. There was a slight increase in MSA during head-up tilting to 40 degrees, and orthostatic hypotension (OH) occurred just after the body was tilted head upward to 40 degrees. MSA became prominent 30 minutes after the oral administration of 200 mg of L-threo-DOPS while the patient was in a 40 degree head-up position, and the OH was improved. The MSA discharge rate decreased and OH reappeared 3 hours after oral administration, when the plasma concentration of norepinephrine was at its highest level. We suggest that the OH improved mainly because of the increase in MSA due to L-threo-DOPS, and that the drug may activate sympathetic outflow at a site proximal to the sympathetic ganglion.

Duration of the first agonist EMG burst in ballistic arm movements.

In normal subjects, fast arm movements are accomplished by a diphasic or triphasic EMG activation of the agonist and antagonist muscles. The duration of the first agonist burst (Ag1) has been said to be constant for movements of different size, whilst its amplitude is variable. Previous studies focused on relatively small movements (10-40 degrees). We have studied the behaviour of the Ag1 duration over the full physiological range of wrist and elbow flexion movements in normal subjects. The results showed that the principle of invariance of Ag1 duration was true when small movements of about 15-30 degrees were studied, but when larger movements were made burst length increased. A similar increase in Ag1 burst duration also was seen during movements performed against a load and in contractions made with fatigued muscles. Changes in duration of the Ag1 burst appear to be part of the normal mechanism for increasing the impulsive force provided in rapid contractions.

Chronic progressive sensory ataxic neuropathy: clinicopathological features of idiopathic and Sjögren's syndrome-associated cases.

Eleven patients with chronic progressive sensory ataxic neuropathy were examined clinicopathologically. Three cases were associated with primary Sjögren's syndrome (SS-SAN) and the others were considered to be idiopathic (ISAN). The major clinical symptom in both was loss of proprioceptive and kinesthetic sensation with some impairment of superficial sensation, with multifocal and asymmetrical distribution and progression. The truncal and trigeminal nerves were frequently involved. The motor system was substantially preserved. These somatic sensory and motor symptoms did not differ between ISAN and SS-SAN, but autonomic nervous system signs were more frequent in SS-SAN. Polyclonal elevations of serum IgG and/or IgA were seen in 8 patients. One autopsied case with ISAN combined with previous reports suggested that systemic T- and B-cell infiltration into the nervous tissues, as well as a wide variety of the visceral organs, may be a common finding in ISAN and SS-SAN, and could participate in the cause of this neuropathy and polyclonal hypergammaglobulinaemia.

Differences between adrenaline and noradrenaline cells in cellular association with supporting cells in the adrenal medulla of the pig: an immunohistochemical study.

Location and morphology of glial supporting cells in the pig adrenal medulla were examined immunohistochemically by the ABC method using antibody to S-100 protein. In noradrenaline (NA)-cell regions, S-100-positive cells were located in both marginal and internal portions of the parenchyma, extending fine cytoplasmic processes between NA cells and/or enveloping large surface areas of NA cells. In adrenaline (A)-cell regions, S-100-positive cells were present less frequently than in NA-cell regions, mostly in the marginal portion of the parenchyma. It is surmised that differences between A cells and NA cells in cellular association with supporting cells reflect those in biological characteristics.

Age-related changes in brain neuromagnetic responses to face perception in humans.

In order to investigate the effects of ageing on face perception, we studied the magnetic responses to face images in 15 young (19-38 years) and 10 elderly (51-81 years) subjects. Face-specific responses (160mF), which originate in the inferior occipitotemporal cortices, and face non-specific responses (100m), which originate in the primary visual cortices, were evoked in all subjects. Averaged peak latency of the 160mF in the elderly group (174.0+/-9.1 ms) was significantly longer (P<0.0005) than that in the young group (161.5+/-5.1 ms), while no inter-group difference was found in the 100m latency. There was a significant correlation between age and 160mF latency (+0.35 ms/year, R=0.747) suggesting age-related decline of face perception.

Pain-related somatosensory evoked potentials in dementia.

Pain-related somatosensory evoked potentials (pain SEPs) were examined in 25 demented and non-demented patients to investigate the cognitive function for pain in the progression of dementia. Pain SEPs by CO2 laser stimulation were recorded together with auditory event-related potentials (auditory ERPs). P340 in pain SEPs and P300 in auditory ERPs were analysed. The latency of P300 evoked in mildly demented patients was inversely correlated with the Mini-Mental state examination score, and the latency of P340 was also inversely correlated to that score but to a lesser extent. Pain SEPs were not recorded in 4 of 7 severely demented patients. These results indicate that the P340 component of pain SEPs is apparently different from the P300 component of auditory ERPs and suggest that the pain perception in severely demented patients may be abnormal.

Auditory and visual event-related potentials and flash visual evoked potentials in Alzheimer's disease: correlations with Mini-Mental State Examination and Raven's Coloured Progressive Matrices.

We investigated possible correlations among neurophysiological examinations [auditory and visual event-related potentials (A-ERPs, V-ERPs), and flash visual evoked potentials (F-VEPs)] and neuropsychological tests [Mini-Mental State Examination (MMSE) and Raven's Coloured Progressive Matrices (RCPM)] in 15 subjects with probable or possible Alzheimer's disease (AD) according to the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria. The P300 latency of A-ERPs was correlated with the scores of MMSE but not with those of RCPM. The P300 latency of V-ERPs was more significantly correlated with the scores of RCPM than with those of MMSE. The P2 latency of F-VEPs was more significantly correlated with the scores of RCPM than with those of MMSE. The P2 latency of F-VEPs was not correlated with the P300 latency of A-ERPs but was correlated with the P300 latency of V-ERPs. The close relationship among V-ERPs, F-VEPs and RCPM suggests that these examinations at least partly reflect the functions of visual association areas in AD. Furthermore, discrepancy between P300 latency by A-ERPs and V-ERPs suggests that the mechanism responsible for P300 generation is not identical between these two stimulus modalities.

Somatic motor efferents in multiple system atrophy with autonomic failure: a clinico-pathological study.

The myelinated fibers in the corticospinal tracts, ventral spinal roots, and the neurons in the ventral spinal horns were quantitatively examined in 8 autopsied cases of multiple system atrophy associated with autonomic failure. In these structures consisting of the somatic motor efferents, the main pathological feature was the size dependent-involvement of predominantly small-sized fibers and neurons. The small myelinated fibers were significantly depopulated, while the large myelinated fibers were well populated in the corticospinal tract. Neurons in the ventral horns were also involved, but those with a small diameter and located in the intermediate zone (Rexed's lamina VII, VIII) were markedly diminished. In the ventral spinal roots, in the fourth lumbar segments containing essentially no autonomic efferents, small myelinated fibers were also preferentially involved. These pathological changes in the small-sized fiber and neuron loss were examined in relation to the somatic and autonomic motor symptoms, particularly of pyramidal signs.

Magnetic resonance imaging of the corticospinal tracts in amyotrophic lateral sclerosis.

In 13 patients with amyotrophic lateral sclerosis (ALS), corticospinal tract lesions on spinal cord, brain and brain stem were examined by MR imaging. In 9 patients, areas of high signal intensity located in the dorsolateral columns coinciding with the lateral corticospinal tracts, were detected on axial T2*-weighted MR imaging of the cervical spinal cord using a gradient echo technique. In two patients, these spinal cord MR abnormalities corresponded well to the postmortem pathological findings of lateral corticospinal tract degeneration. T2-weighted abnormal MR signals along the corticospinal tract at the brain and brain stem were detected in 4 patients, all of whom also showed abnormal signals on cervical cord MR imaging. Four of 13 patients did not show any abnormal signals on brain and brain stem or spinal cord MR imaging. Spinal cord MR imaging provides a useful information regarding upper motor neuron lesions in ALS.

Aberrant androgen action and increased size of tandem CAG repeat in androgen receptor gene in X-linked recessive bulbospinal neuronopathy.

Plasma levels of testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) after 3 or 6 days of administration of the synthetic androgenic hormone fluoxymesterone (10 mg/day) were measured in 26 patients with X-linked recessive bulbospinal neuronopathy (X-BSNP) and 22 age-matched male controls. The testosterone, LH and FSH levels in the controls were markedly suppressed after administration, but in the patients with X-BSNP, they were suppressed significantly less. The level of suppression varied considerably with the patients, and those of plasma testosterone and FSH were significantly correlated with the number of CAG repeats in the androgen receptor gene. These findings suggest that the androgen action was aberrantly transduced in the target organs in the patients with X-BSNP and which is related to the elongated CAG repeat in the androgen receptor gene.

Subclinical phenotypic expressions in heterozygous females of X-linked recessive bulbospinal neuronopathy.

Four of 8 definite heterozygous female carriers determined by PCR amplification of tandem CAG repeat of the AR gene, from 4 families of X-linked recessive bulbospinal neuronopathy (X-BSNP) showed extensive high amplitude motor unit potentials in examined muscles although all subjects were neurologically normal. Plasma creatine kinase, myoglobin, myosin light chain, lactate and pyruvate were all normal even in the carriers who showed EMG abnormalities. Muscle biopsy showed a type 2 fiber preponderance and possible very mild type 2 fiber grouping in a carrier with an EMG abnormality. These results suggest that a mutant AR gene may express subclinical phenotypic manifestations in a subpopulation of the heterozygous females of X-BSNP.

Pain-related and electrically stimulated somatosensory evoked potentials in patients with Machado-Joseph disease and multiple system atrophy.

We investigated the ascending somatosensory pathway for pain in 8 patients with Machado-Joseph disease (MJD) and multiple system atrophy (MSA). Pain-related somatosensory evoked potentials (pain SEPs) by CO2 laser stimulation were examined together with conventional electrically stimulated somatosensory evoked potentials (electric SEPs). The sporadic cerebellar ataxia of patients with MSA showed a normal pattern of pain SEPs as well as electric SEPs. However, pain and electric SEPs were abnormal for the central and/or peripheral ascending pathway in MJD. These abnormalities of pain and electric SEPs in MJD were not related to the clinical severity of sensory impairment, but they indicate that MJD presents a subclinical abnormality for the ascending somatosensory pathways not only for vibratory sense but also for pain sense.

Sensory conduction study of cisplatin neuropathy: preservation of small myelinated fibers.

We report a patient with peripheral neuropathy caused by cisplatin for the treatment of testicular tumor. Routine studies of nerve conduction and somatosensory evoked potentials demonstrated large myelinated fiber neuropathy suggesting ganglioneuronopathy. We also performed a CO2 laser evoked potential study, and found that small myelinated fibers, which are related to pain sensation, were well preserved in this patient.

Humoral hypercalcemia of malignancy associated with parathyroid hormone-related protein producing transitional cell carcinoma of the ureter.

A 78-year old male with ureteral carcinoma manifesting hypercalcemia is reported. He was diagnosed as having ureteral carcinoma of the left side 2 years previously and was treated by nephrectomy with ureterovesicostomy. In October 1991, he was admitted for anorexia. A clinical examination revealed recurrence of the ureteral carcinoma with metastasis to the rectum and liver. His serum calcium level was elevated (13.9 mg/dl). In addition to rehydration and furosemide, treatment with eel-calcitonin and prednisolone failed to decrease his serum calcium level. Finally, he was administered mithramycin but he died 13 days later. He had no evidence of bone metastasis or hyperparathyroidism. Nephrogenic cAMP and urinary parathyroid hormone-related protein (PTHrP) were markedly elevated. Immunohistochemical study demonstrated expression of PTHrP in the tumor cells. Thus, the hypercalcemia was thought to be mediated by PTHrP secreted from the neoplastic tumor. Although there have been several reports of ureteral carcinoma associated with humoral hypercalcemia of malignancy, this is considered to be the first case associated with elevation of PTHrP.

[Medical treatment of dystonia].

The treatment of dystonia is exclusively difficult. Recently botulinum toxin has been introduced into the market, but its indication is still limited. Oral administration of high dosage of anticholinergic drugs is firstly recommended for the treatment of dystonia. Effective cases usually do not show obvious side effects. Likely, diazepam is another choice, and the drug usually does not bring any adverse effect in cases with good results. Effects of other drugs such as l-dopa and antidopaminergic agents are still under discussion. In cases with myoclonus and/or tremor clonazepam can be useful for improvement of the phasic symptoms. As the prognosis of dystonia especially that of focal dystonia is not hopeless, the patients with dystonia should be informed of the facts.

[Pathophysiology of involuntary movements--dystonia and myoclonus. Symptomatological view].

Among involuntary movements, dystonia is defined as abnormal posturing produced by slow sustained muscle contractions. On the contrary, myoclonus is characterized by sudden shock-like contractions of a muscle or a group of muscles. The electromyogram (EMG) in dystonia shows continuous activity lasting 5 seconds or more. The muscles usually co-contract in the antagonists. In myoclonus the muscle bursts on EMG last usually between 10 and 50 ms. In some cases the bursts last longer, but they are 200 ms at most. Thus, the characteristics of myoclonus is quite different from those of dystonia. There are, however, unusual combination of dystonia and myoclonus. Myoclonic dystonia, in which myoclonic jerks are so severe that crucial dystonic posturing may be ignored, has been reported. Essential tremor, writing tremor and writer's cramp (writing dystonia) and myoclonic writer's cramp are sometimes seen in one family in various combination. It is suggested that there may be pathophysiological relationship between dystonia and myoclonus, although these two movement disorders have different clinical characteristics.

[Pathology of the peripheral nervous system in polyarteritis nodosa: a clinico-pathological study of two autopsy cases].

Peripheral nerves from the two autopsied cases with polyarteritis nodosa were pathologically examined. Case 1 was a seventy-year-old female, complaining of numbness and weakness of the extremities. Sensory deficits in all modality with induced dysesthesia were distributed as a mode of overlapping mononeuritis multiplex in the distal portion of extremities. Motor involvement was also noted in extremities in disarray-accentuated pattern. Extensive steroid hormone therapy was performed and remarkable improvement in clinical sign was temporarily obtained. Relapse with bowel involvement was a cause of the death. In the post-mortem examination, central fascicular degeneration with the loss of large myelinated fibers were seen at the middle portion of upper limbs in median nerve and at the lower mid-thigh in sciatic nerve. In the distal portion of those nerves, diffuse extensive loss of large myelinated fibers in the fasciculus were observed. Some of small thin myelinated fibers in the central fasciculus or distal portion of nerves were thought to be regenerated in nature. Accumulation of cell organelles in the axonal swellings were frequently occurred in the proximal to the ischemic site. Case 2 was a seventy five-year-old female with a both motor and sensory involvement in the distal extremities. Right pulmonary effusion and extensive subcutaneous hemorrhage and necrotic gangrene in the leg was also noted. Post-mortem examination of peripheral nerves revealed a presence of central fascicular degeneration in the distal sciatic nerves and nearly complete loss of myelinated fibers in the distal nerves. Ventral and dorsal roots and dorsal root ganglia were well preserved.(ABSTRACT TRUNCATED AT 250 WORDS)

[Spatial distribution of the peripheral nerve lesion in polyarteritis nodosa].

We have examined the peripheral nerves in four patients with polyarteritis nodosa. They were consisted of two males and two females with the age of 70, 49, 65 and 75 years respectively. The sciatic and posterior-tibial nerves, sural nerves, ventral and dorsal spinal nerve roots, dorsal ganglia and spinal cord were removed at autopsy. Particularly, the sciatic and posterior-tibial nerves were removed as a whole and suspended in a glass cylinder with a weight and fixed in 1.5% glutaraldehyde and 0.05 M phosphate buffer, pH 7.4 for 16 hours. The nerve fragments of every 3 to 3.5 cm along the sciatic and posterior-tibial nerve were examined on conventional paraffin-embedded and epon-embedded sections, and osmicated teased-fibers. Necrotizing angitis was commonly present in the epineurium of the sciatic and posterior-tibial nerves in all four patients. Although necrotizing angitis was diffusely distributed in the proximal to distal portions of the nerve, loss of myelinated fibers, occurred only in the distal to mid-lower portions of the sciatic nerve. There was no substantial myelinated fiber loss in the proximal part of the sciatic nerve in three of four cases. Myelinated fiber loss in the fascicle was central fascicular or multiple-focal in pattern in the proximal portions of the nerve, but was diffuse in more distal portion of the posterior tibial nerve. Segmental demyelination and myelin irregularity in the teased-fiber preparation were more prominently observed in the proximal portions, but fibers with axonal degeneration were more frequent in the distal portions of the nerve.(ABSTRACT TRUNCATED AT 250 WORDS)