Rational treatment of diabetic polyneuropathy depends upon establishing its cause, which is at present unknown. A number of animal models of diabetes have been examined and although abnormalities are detectable in the peripheral nervous system they do not duplicate the degenerative neuropathy encountered in the human. The relevance of these abnormalities is therefore uncertain, although they may reflect the earlier changes in man. For human neuropathy, it is likely that vascular lesions or an abnormal susceptibility to mechanical injury are responsible for focal neuropathies. The evidence that ischaemia and hypoxia are responsible for the diffuse sensory neuropathy and autonomic polyneuropathy is still equivocal and it is often difficult to establish whether the vascular changes are primary or secondary. Metabolic explanations, such as sorbitol accumulation in nerve, have not so far been adequately validated by responses to treatment. The manifestations of diabetic neuropathy are complex and a single explanation should not be sought.

The purpose of this experiment was to quantify and analyse multijoint coordination of patients with Parkinson’s disease (N=5) and control subjects (N=5) during forward and backward stepping motions executed at different cadences. Coordinates of reflective markers placed on the shoulder, hip, knee, ankle and metatarsal joints were recorded in the sagittal plane using a video motion analysis system. Kinematic and kinetic analyses provided angular displacements and velocities as well as joint moments of force and powers. Results suggest the presence of two types of discoordination: one type is velocity-dependent, hence related to bradykinesia, whereas the other type appears to reflect qualitatively different coordination patterns.

General protease and collagenase IV activity are involved in the remodelling of the vascular basement membrane that occurs during tumor-induced angiogenesis. This study has assessed the level of these enzymes in tumor, peritumoral or contralateral cerebral cortex tissue during the growth of C6 astrocytoma in the rat spheroid implantation model. General proteolytic activity was increased in tumor tissue beginning on day 8 following spheroid implantation, then increased to a maximum value on day 11 and decreased to control values on day 18. A similar pattern was seen for collagenase IV activity but maximal activity occurred on day 13. The peritumor and tumor patterns of activity were similar. General protease activity was increased in the hemisphere contralateral to the tumor suggesting that the growth of C6 astrocytoma in rat brain was influencing biochemical events distant from the tumor. C6 astrocytoma cells orchestrate a cascade of proteolytic events which may play a crucial role in angiogenesis associated with tumor growth in the model system studied.

Microfilaments and microtubules play a part in the extension of neuronal processes but their roles in the formation of glial processes have not yet been determined. The objectives of this study were to determine the organization of microfilaments in differentiating glial progenitors (RB2 cells) and to study the effects of microfilament or microtubule disruption on process extension. Intense F-actin staining (crown of microfilaments) was observed at the leading edge of a small extending conical tip in differentiating RB2 cells, but was absent in process-bearing TE671 rhabdomyosarcoma cells. No significant difference was noted in the mean number of TE671 cells with processes treated with a microfilament disrupter from that of similarly treated controls. In contrast, a significant difference was noted in the mean number of RB2 cells with processes after microfilament disruption treatment from that of similarly treated controls. Microtubule disruption arrested extension and caused process retraction in both cell types. The results of this study demonstrate that microtubules play an equally important part in the extension and stabilization of the RB2 and TE671 processes. Moreover, the crown of microfilaments concentrated in the glial RB2 process (and not in the TE671 process) may be critical to its extension during differentiation.

Contrast enhancement on computerized tomography (CT) scans has been used in directing therapy for presumed intracranial gliomas. However, for moderately anaplastic astrocytomas (MOAAS) and highly anaplastic astrocytomas (HAAS), it provides no information about proliferative potential. The bromodeoxyuridine (BUDR) labeling index (LI), however, indicates proliferative potential, correlating with histologic malignancy and survival. An LI < 1% is a favorable indicator; LI > 5% suggests more aggressiveness. To determine the correlation, if any, between BUDR LI and contrast enhancement, CT scans of 71 patients with cerebral hemisphere tumors labeled with BUDR were retrospectively reviewed. Among 36 MOAAS, the BUDR LI was < 1% in 77% of enhanced tumors and 61% of unenhanced tumors. Among 35 HAAS, it was < 5% in 56% of enhanced tumors and 90% of unenhanced tumors. Therefore, contrast enhancement on CT scans does not always correctly predict proliferative potential in these tumors, and biopsy and labeling studies are recommended before therapy.

Despite the great capacity for the pediatric brain to recover from stroke, the morbidity and mortality in children who harbor an arteriovenous malformation (AVM) remains high. This study examines the clinical data and management experience with 132 patients with brain AVM from 1949 to 1989. Although the high tendency for a childhood AVM to present with hemorrhage (79%) remained constant for the forty year study period, the associated morbidity and mortality of hemorrhage changed. The mortality rate from hemorrhage for the entire series was 25%, which was reduced from 39% to 16% after the introduction of computed tomography. The mortality from AVM hemorrhage since 1975 was dependent on location; 8 of 14 patients (57%) with a cerebellar AVM died from hemorrhage while only 2 of 44 patients (4.5%) with a cerebral hemisphere AVM died (p < 0.0001). Sixteen children (12%) presented with a chronic seizure disorder. Surgical excision of the malformation resulted in complete seizure control off anti-convulsant medication in 73% of patients. Although 21% of patients were treated non-operatively (many with terminal poor-grade hemorrhage), 79% had a surgical procedure with total AVM excision achieved in 70 patients (53.1%). Complete AVM resection was followed by a normal neurological outcome in 47 children (67%). Most partial excisions (n=9) and clipping of feeding arteries (n=7) were performed in the early years of this study, and did not provide protection from rehe-morrhage. Although conservative management has been advocated for selected non-hemorrhagic AVMs, we conclude that essentially all children with an AVM should be treated in order to eliminate the risk of hemorrhage. Long-term conservative management in pediatric patients is warranted only in patients with large AVMs not amenable to treatment using current multimodality techniques.

Four children with Landau-Kleffner syndrome were studied over a six year period. They presented with acquired aphasia, epilepsy, and focal or generalized EEG discharges which were exacerbated during sleep. In addition, cerebral angiography demonstrated isolated arteritis of some branches of the carotid arteries in all cases. Computed tomographic and magnetic resonance images were normal. Nicardipine in a dose of 1 to 2 mg/kg/day, added to conventional anticonvulsant drugs provided effective supplementary control of seizures, of paroxysmal EEG discharges, and of language and behavioural disturbances, even several years after the onset of the disorder and in patients whose response to other medications, including steroids, had been poor. Interruption of nicardipine administration was followed by relapse of the language disorder. Repeat angiography was performed in all four patients and showed recanal-ization of obstructed vessels in two cases. Focal cerebral vasculitis may be the pathogenesis of the Landau-Kleffner syndrome and calcium channel blockers such as nicardipine may be effective and specific therapy.

Discontinuous non-circumferential lesions of tunica media were observed in four cases of traumatic rupture of the vertebral artery. We hypothesize that these lesions were due to mechanical disruption of smooth muscle cells and the liberation of catabolic enzymes with subsequent degradation of the arterial media. To test this hypothesis, healthy vertebral arteries were incubated with crude extracts of bovine smooth muscle cytosol in attempt to reproduce the histological changes of the arterial media in traumatized vertebral arteries. We observed cytosol-induced degradation of tunica media, characterized by pallor of staining with the Masson’s Trichrome method, which was due to catabolic enzyme activity that was effectively inhibited by heat inactivation of the cytosol. The cytosol-induced tinctorial changes were similar to the lesions of the tunica media in naturally-occurring cases of traumatic vertebral artery rupture. We conclude that although vertebral arteries can be ruptured by physical distortion alone, associated lesions of the tunica media are due to in situ trauma-associated release of heat-labile catabolic enzymes.

Two patients with pure motor hemiplegia were regaining strength in the affected limbs when a pure motor stroke developed on the opposite side. At the same time as the new hemiplegia appeared, the recovering side became re-paralyzed, suggesting that activity in the contralateral corticospinal tract had participated in the recovery process. Pathological studies were confirmatory. The literature pertaining to contralateral motor compensation is reviewed.

The purpose of this investigation was to compare three methods of assessing the excitability of lower motoneurones—TA-reflex, H-reflex and F-wave—in 120 patients with spastic hemiparesis following a stroke. The H-reflex was recorded from the soleus muscle after submaximal electrostimulation of the tibial nerve. The T-Achilles (TA) reflex was recorded from the soleus muscle after percussion of the Achilles tendon. The F-wave was recorded in the distal limb muscles after supramaximal electrostimulation of the median, ulnar, fibular and tibial nerves. The patient’s healthy side was used as a control. The TA-reflex, H-reflex and F-wave showed increased amplitudes on the spastic side. All amplitude ratios: TA/M, H/M, Fmax/M and Fmean/M were increased. The H-reflex thresholds were decreased. The F-wave duration, persistence and number of phases were also increased on the spastic side. Despite clinically decreased muscle tone, there were no changes in TA or H-reflex parameters after treatment. On the other hand, F-wave parameters tended to normalize after treatment in all groups. In conclusion, the F-wave is a more sensitive method than the TA and H-reflexes in assessing the excitability of the lower motoneurone.

Previous studies using subjective tools to measure pain have shown that muscle exercise can have analgesic effects in man. The nociceptive leg flexion reflex (or RIII reflex) is a useful objective tool for assessing human pain. In this study, the pain threshold was assessed using the nociceptive flexion reflex in six high-level athletes 1) at rest in comparison with 8 control subjects and 2) after exercise requiring the production of a 200-Watt force over a period of 20 minutes. The nociceptive flexion reflex threshold at rest was found to be spontaneously higher in the athletes than in the controls. Physical activity resulted in a significant increase (+53%) in the threshold of the nociceptive reflex in the athletes. The role of stress-induced analgesia, the reduction in perceived intensity of stimuli during movement, and the release of opioids are discussed.

A prevalence study of multiple sclerosis (MS) was carried out in the town of Barrhead and surrounding county of Barrhead, in Alberta, Canada. The prevalence rate for clinically probable/definite multiple sclerosis on January 1, 1990 was 196/100,000. The average annual incidence rates for patients living in the area at onset were 1.31/100,000 for 1950–59, 4.97/100,000 for 1960–69, 3.77/100,000 for 1970–79, and 4.22/100,000 for 1980–89. Fifty per cent of the patients were relapsing-remitting. Sixty per cent were still walking without assistance. The female-to-male ratio was 1:1. Mean current age, age at onset and duration of illness were 49, 27 and 22 years respectively. The majority of patients (40%) experienced multiple symptom onset. Fifty per cent were of single ethnic origin (either British or German); the rest were predominantly North European combinations. Forty per cent of patients reported another MS relative. MS had affected the work status of 60% of the patients, 15% of whom were confined to an extended care centre.

Congenital motor nystagmus (CMN) can be familial or non-familial. The expressivity of CMN is so variable that in one affected member of the family the oscillations are obvious, while in the others the nystagmus could be overlooked even by the patients themselves. In spontaneous cases the proof of heredity might be discovered by an ophthalmological examination or eye movement recordings of other family members. Our multidisciplinary studies of 27 children with CMN suggests that a neurodevelopmental assessment can also be valuable in establishing a diagnosis of heredity. Our studies suggest that the hereditary form of CMN is free from neurodevelopmental problems, while the non-familial form is not. Therefore, children with spontaneous CMN could be referred for neurodevelopmental evaluation in order to establish a more accurate diagnosis.

In a patient with pure autonomic failure, exercise did not modify beta-adrenoceptor density, probably due to an insufficient increase in plasma catecholamines. Isoproterenol infusion increased the number of beta-adrenoceptor by only 17%. Since in control subjects an increased beta-adrenoceptor level was found, following both physical stress and isoproterenol infusion, we suggest that the lack of increased beta-adrenoceptor levels may contribute to the poor circulatory adjustments observed in autonomic dysfunction during activities involving the sympathetic nervous system.

Tuberculous meningitis may rarely be followed by the development of syringomyelia despite appropriate chemotherapy. In the present paper, we report a case of tuberculous meningitis in a 23-year-old Vietnamese male complicated by a rapidly progressive myelopathy due to granulomatous arachnoiditis which culminated in the development of a syrinx. The relevant literature is reviewed. The present case supports the hypothesis that vasculitic thrombosis of spinal cord vessels leading to ischemic myelomalacia is the mechanism causing postinflammatory syringomyelia.

Immune-mediated myasthenia gravis occurred in a 13-month-old girl who had sequelae of an opsoclonus-myoclonus syndrome. She had an abnormal Raji cell assay along with elevated antiacetylcholine receptor and antithyroglobulin antibodies. No evidence of an associated malignancy was found with either condition. Clearly, the co-occurrence of two diseases within a single patient does not establish a common pathogenesis. Nevertheless, this is a provocative association and may point to an immunologically mediated process in the opsoclonus-myoclonus syndrome.

H. ITO, A. HIRANO and S.-H. YEN (Bronx, U.S.A.)

The parkinsonism-dementia complex (PDC) on Guam is characterized histopathologically by neuronal loss in widespread areas and by the presence of numerous Alzheimer’s neurofibrillary tangles in certain neuron groups. It has been reported that in Guamanian PDC patients there is virtually no plaque formation. Prior to 1965, the existence of argentophilic plaques has been investigated in only a few Guamanian cases. However, from more recent studies, there is evidence on plaque formation in a relatively high proportion of Guamanian patients. To determine whether this change is due to differences in the detection techniques, we have re-evaluated with an immunoperoxidase method the archival material used in earlier studies.