To characterize kinematically any systematic aberration in multi-joint movements in cerebellar ataxia.

Nine patients with cerebellar degeneration and nine normal subjects, mobile only at the shoulder and elbow of the right arm, were required to produce left-to-right cross-body linear hand trajectories on the horizontal surface of a digitizing tablet. Nonlinearity indicated failure of precise coordination of the two joints. A wide range of hand speeds was studied. Data analysis was restricted primarily to the first 130 ms of movement.

As hand velocities increased, normal subjects and, especially, patients produced misdirected, curved paths. Normal subjects had significant curvature when peak speeds exceeded 100 cm/s and a trend toward significant bi-directional angular deviation at velocities greater than 300 cm/s. In patients, peak path curvature was significantly greater than normal at peak velocities of 50 to 200 cm/s. By 3.3 cm, their paths deviated significantly outward at all but the slowest speeds. Overall, patients’ maximal hand velocities and shoulder angular velocities, as well as maximal angular accelerations at both joints, were significantly lower than normal.

The patients’ trajectory aberrations were attributed to a deficient rate of rotation at the shoulder relative to that at the elbow. Relative to task requirements, their rate of torque development was apparently deficient at both joints, but to a greater degree at the shoulder. Joint torque-rate impairment may contribute to the ataxia in both multi- and single-joint movements of patients with cerebellar disorders. A similar, but smaller impairment may produce milder nonlinearity in high-velocity movements of normal subjects.

Previous reports have described changes in reciprocal la inhibition in hémiplégie patients, but correlations between the amount of la inhibition and the clinical deficits have not been well established.

We studied reciprocal inhibition between ankle flexors (tibialis anterior) and extensors (soleus) in 16 hemiplegic patients at various stages following a stroke and in 26 control subjects. The amount of disynaptic la inhibition was determined from the short latency suppression of the soleus or tibialis anterior H-reflexes by conditioning stimulation of the antagonistic muscle nerves.

Disynaptic la inhibition from peroneal nerve afférents to soleus motoneurones was increased in patients who showed good recovery of function with mild spasticity. However, it was not changed, or even sometimes diminished, in patients who made a poor recovery and had more marked extensor spasticity. In patients where serial recordings were obtained there was an increase in la inhibition during the recovery period following stroke. la inhibition to the tibialis anterior motoneurones tended to be greater in the poor recovery patients with marked spasticity than in the good recovery patients. The late (Dl) inhibition, presumably due to presynaptic inhibition, was decreased in the patients, although consistent correlations between the amount of this inhibition and the clinical features were not clearly demonstrated.

Changes in excitability of la inhibitory pathways can be correlated with some of the clinical features seen in hemiplegia. Increased la inhibition of soleus motoneurones during recovery may be a mechanism to compensate for loss of descending motor commands.

Although the pathogenesis of sudden infant death syndrome (SIDS) is not understood, one of the major hypotheses is that a subtle defect in respiratory circuitry is an important underlying factor. The vagus nerve is a critical component of respiratory control, but its neuroanatomic complexity has limited its investigation in human disease.

Correlating developmental studies on different parts of the vagus nerve allows a more comprehensive assessment of its maturation process. Comparison of the normal developing vagus nerve with nerves examined in SIDS patients suggests alterations in the nucleus tractus solitarius and dorsal vagal nucleus as well as in the peripheral vagus nerve.

The persistence of dendritic spines and lack of appropriate axonal growth implies delays in vagal maturation. Since nodose ganglia can be examined in vitro from autopsy material, perturbation to this system can be explored to evaluate further the mechanism involved in terminal vagal maturation. Although the reason for the delayed vagal maturation in SIDS is not apparent, the presence of astrogliosis in the region of the vagal nuclei is consistent with an exposure to hypoxic-ischemic events some time before death.

CT and MR guided stereotactic techniques have provided promising results in the management of brain abscesses. We reviewed our results of stereotactic management of brain abscesses in 20 consecutive patients with 28 abscesses from 1986 to 1993.

13 abscesses were in the cerebral hemispheres, 12 in the cerebellum, 2 in the pons and 1 in the thalamus. The bacterial organism was isolated in 12 of the 20 cases. All patients, except one who had a tuberculous abscess, were on antibiotics for less than 7 weeks.

Although there were 3 patients in coma before surgery, the mortality rate was zero and 17 patients had an excellent recovery with 3 patients having a persistent mild neurologic disability. Stereotactic aspiration of the largest lesion in the patients with multiple brain abscesses combined with intravenous antibiotic therapy was sufficient for the resolution of all lesions. Two of our patients treated with antibiotics alone showed abscess progression with neurologic worsening.

Stereotactic aspiration is safe, accurate, and when combined with the appropriate antibiotics, should be considered the procedure of choice in the management of brain abscesses.

Acute hydrocephalus is a potentially treatable cause of early neurological deterioration after aneurysmal subarachnoid hemorrhage (§AH).

A retrospective study of 105 consecutive cases of aneurysmal SAH was undertaken to determine those factors significantly related to the development of acute hydrocephalus. Acute hydrocephalus was diagnosed when the bicaudate index was greater than the 95,h percentile for age on a CT scan within 72 hours of the ictus.

Thirty-one percent of the patients developed acute hydrocephalus. Grade of SAH was a significant factor for the development of acute hydrocephalus on univariate analysis as 87% of patients with acute hydrocephalus (29/32) presented with at least grade 3 (Hunt-Hess) SAH (p < 0.05). In addition, posterior circulation aneurysms on univariate analysis were associated with acute hydrocephalus (p < 0.05). Both premorbid hypertension and intraventricular blood (p < 0.05) were predictors for acute hydrocephalus, whereas intracisternal blood, age and sex were not. On multivariate linear regression analysis, factors found to be significantly associated with acute hydrocephalus were premorbid hypertension, intraventricular blood, CSF diversion and definitive shunt procedures. External ventricular drainage was not associated with any instances of rebleeding. Thirty-seven percent (10/27) of patients with acute hydrocephalus who survived were improved by pre-operative external ventricular drainage.

Patients with acute hydrocephalus following SAH can be safely treated with external ventricular drainage. Multiple factors can be identified to predict those patients who will develop acute hydrocephalus post aneurysmal rupture. Approximately 30% of those patients with acute hydrocephalus will require definitive shunt placement. Acute hydrocephalus occurred in 31% of aneurysmal SAH patients in this series.

The purpose of the present investigation was to determine if post-ischemic treatment with the 21-aminosteroid lipid peroxidation inhibitor tirilazad mesylate (U-74006F) could affect reperfusion brain edema during the first 3h following a 3h period of middle cerebral artery occlusion-induced focal ischemia in cynomolgus monkeys.

Adult female cynomolgus monkeys (N = 14) were subjected under halothane anesthesia to a 3h period of middle cerebral artery occlusion, followed by 3h of reperfusion. U-74006F, 3.0 mg/kg i.v. or citrate vehicle, was administered 10 min before beginning reperfusion. Multiple spin-echo (8 echoes: TE = 26.3 msec; TR = 3.0 sees; 2.35 Tesla) magnetic resonance imaging was performed every 30 min, beginning at lh after reperfusion. Transverse relaxation rates (T2) for the caudate, putamen, cortex, insular cortex, parietal cortex and central white matter were calculated as an index of focal brain edema. After the final images, corresponding regions were removed for determination of water content by the wet weight/dry weight method.

The T2 measurements strongly suggested the presence of post-reperfusion edema in all gray matter, but not white matter, regions at 1 h after reperfusion in vehicle-treated animals. Significant attenuation of edema development was seen in the putamen and insular cortex in U-74006F-treated animals. An effect was also observed in the parietal cortex, but none in the caudate. The measurement of water content at 3h after reperfusion yielded similar results.

These results showing the ability of U-74006F to attenuate post-reperfusion brain edema support the concept that lipid peroxidation is a significant mediator of reperfusion brain edema after focal ischemia. The therapeutic window for U-74006F’s anti-edema effect appears to be at least 3h after the onset of focal ischemia since delaying treatment until just before reperfusion largely prevented subsequent edema in cortical regions and the putamen. The effects of U-74006F on edema may play a mechanistic role in the compound’s reported neuroprotective efficacy in a variety of focal ischemia models.

Symptomatic (secondary) dystonias associated isolated lesions in the brain provide insight into etiopathogenesis of the idiopathic form of dystonia and are a basis for establishing the possible correlation between the anatomy of a lesion and the type of dystonia according to muscles affected.

In 358 patients with differently distributed dystonias, a group of 16 patients (4.5%) was encountered in whom dystonia was associated with focal brain lesions.

Of the 16 patients, 3 patients had generalized, 3 segmental and 4 hemidystonia, while the remaining 6 patients had focal dystonia. The most frequent etiologies were infarction in 7, and tumor in 4 patients. These lesions were usually found in the lenticular and caudate nucleus, thalamus, and in the case of blepharospasm in the upper brainstem.

Our results support the suggestion that dystonia is caused by a dysfunction of the basal ganglia.

A retrospective, population-based, case-control study was carried out to evaluate episodes of prior intra-operative hypotension as a potential risk factor for Alzheimer’s disease (AD).

Patients were all incident cases of AD from 1975–1984 who resided for 40 years or more in Olmsted County prior to their onset of dementia (N = 252). One age and gender-matched control for each case was selected from all registrations for care at Mayo Clinic during the year of onset in the incident case. Each case and control group had 252 individuals.

Of these, 27 cases and 32 controls had at least one ten minute or longer episode of intra-operative hypotension of a systolic blood pressure of less than 90 mm Hg prior to the year of onset of dementia in the matched AD patient. We did not find a significantly increased risk of AD for hypotensive episodes of less than 75 or 90 mm Hg.

It is unlikely that intra-operative hypotensive events of this degree increase the risk of AD.

Secondary (symptomatic) narcolepsy is rare. We report a subependymoma of the fourth ventricle associated with narcolepsy. The patient was a 50-year-old woman with a long history of narcolepsy who died of colonic carcinoma with no cerebral metastasis. She was positive for HLA-DR2. At autopsy there was a tumour dorsal to the fourth ventricle which involved the midbrain tectum and rostral pons. Histologic examination of the tumour confirmed it to be a subependymoma.

Review of the previous cases of secondary narcolepsy was made with particular reference to the anatomical location of the lesions.

Most of the lesions were found around the third ventricle and rostral brainstem.

Knowing the anatomical localization of the pathological changes in secondary narcolepsy could be important in improving our understanding of its pathogenesis.