Pathophysiology of chronic communicating hydrocephalus in dogs (Canis familiaris). Experimental studies.

A model designed to produce chronic communicating hydrocephalus in dogs has been developed in our laboratory. The animals tolerate the procedure well and the yield of animals with communicating hydrocephalus is high. Serial cisternograms show ventricular entry first with "clearing" and later with "stasis". CSF pressures are initially increased, but when the ventricles become enlarged the pressure falls into the normal range. Grossly there is generalized ventricular enlargement and, on histological studies, the ependyma is flattened and denuded. Periventricular edema occurs in the white matter. Autoradiographs show transependymal movement of protein. CSF production appears to be normal despite obstruction to flow of CSF to areas where resorption is greatest. Diversionary shunting probably produces relief of many of the neurological symptoms by providing an efficient pathway for the removal of CSF and thus by lessening edema and ventricular enlargement. A more appropriate treatment would appear to be a noninvasive method of decreasing CSF production. Only when the basic pathophysiological alterations of CSF production and absorption are understood will this be possible. We believe that this animal model affords us the opportunity of studying these mechanisms.     

Experimental cerebral infarction. Part 2: Electroencephalographic changes produced by experimental thalamic infarction in dogs

Previously, one of the authors developed a reliable experimental model in dogs for producing cerebral infarction. The EEG increased detection of experimental cerebral infarction, and was useful in predicting ischemic regions or infarction.     

Experimental cerebral infarction. Part 1: Production of thalamic infarction in dogs

Difficulties in achieving focal temporary cerebral ischemia in experimental animals have delayed study of the prevention and treatment of cerebral infarction. We have succeeded in producing focal cerebral infarction by temporary occlusion of brain arteries. Infarction confined to the anterior portion of the thalamus was obtained by simultaneous occlusion of the 4 cerebral arteries: internal carotid, anterior cerebral, middle cerebral and posterior communicating arteries for 60-120 minutes. This experimental model in dogs is unique, since thalamic infarction can be produced with high frequency, and the dogs can be kept alive and managed for sufficient periods after temporary artery clipping. With this model it is possible to investigate cerebral infarction not only from the pathophysiological viewpoint, but also from the viewpoint of prevention and treatment of cerebral infarction in man.     

Experimental syringomyelia in rabbits and rats after localized spinal arachnoiditis]

In order to produce syringomyelia, localized arachnoiditis was created in adult New Zealand albino rabbits and Wistar rats by the injection of kaolin into the thoracic spinal subarachnoid space and incision of the dura mater of the thoracic spinal cord. The rabbits and rats were divided into 3 groups; the control group, dural incision group (DG) and kaolin injection group (KG). Each rabbit was sacrificed at 4, 8, 12 and 16 weeks after the operation. Each rat was sacrificed at 8 and 16 weeks after the operation. Cavity formation in the cord of all rabbits was examined by ultrasound. All animals were perfused with 10% neutral beffered formalin at 150 cm H2O pressure, and histological examination was performed with Luxol fast blue (LFB) and hematoxylin and eosin (H&E) stains. Results obtained: (1) Cavity formation was noted in 6 of 16 DG of rabbit (37.5%), 5 of 16 KG of rabbit (31.2%) and 2 of 9 KG of rat (22.2%) with histological verification. With use of ultrasound, cavity was noted in 3 of 16 DG rabbits (12.5%) and 2 of 16 KG rabbits (18.8%). (2) Cavity formation was present in the cord adjacent to the marked adhesive arachnoiditis both in rabbits and in rats. (3) Cavity was noted in the ischemic area. (4) In 2 rabbits in which kaolin encircled whole surface of the spinal cord, hydromyelia was formed communicating with enlarged central canal caudad from the kaolin subarachnoid block. (5) Histological examination showed obliteration or narrowing of lumen of the small pial vessels involved in the adhesive arachnoiditis. In the cord parenchyma adjacent to the arachnoiditis, multiple spots of demyelination due secondary to ischemia demonstrated by LFB stain were noted. On the other hand, in the cord with the pia-arachnoid remained uninvolved, no demyelination was observed. (6) Localized adhesive arachnoiditis consisted of proliferation of fibrous tissue, lymphocytic infiltration and obliterating processes of small pial vessels involved in it. These data suggest that the cavitation within the cord would be induced by the ischemia, and hydromyelia would be produced by the pressure dissociation between the spinal subarachnoid space and the central canal.     

Experimental cerebral infarction. Part 3: Protective effect of mannitol in thalamic infarction in dogs

Whether or not mannitol can prevent infarctions in ischemic brain tissues was investigated utilizing the thalamic infarction model in dogs. Twenty dogs were divided into equal control and mannitol treatment groups. Temporary 4 vessel clipping for 60 minutes was adopted as the standard procedure for both groups. The only difference between the groups was the administration of 2 g/kg of mannitol before the arterial occlusion. In the controls, 6 of 10 dogs showed infarctions verified by histological changes at the seventh post-ischemic day. In the mannitol group only 1 dog in 10 showed infarction. The difference is statistically significant.     

Structural alterations in the spinal cord during progressive communicating syringomyelia. An experimental study in the cat

Summary A hydrocephalic-hydromyelic condition was induced in adult cats by causing the closure of the lateral apertures with intracisternal injections of kaolin. After displaying the symptoms characteristic of increased intracranial pressure, which lasted about 10–14 days but varied somewhat in intensity from animal to animal, the cats recovered. From approximately the 2nd post-operative week onward, a distended central canal was revealed by ventriculography; subsequently cavities developed in the tissue of the cord that communicated with the canal. Most cavities were located dorsal to the canal. The surfaces of the distended canal and the cavities showed that in ventral areas the ependyma streched but remained intact, whereas in dorsal areas it ruptured, exposing the nerve fibers to the cerebrospinal fluid (CSF). In cats which had been hydrocephalic for up to 2 years the walls of the cavities were covered by gliotic scar tissue; the nerve fibers were no longer exposed directly to the CSF.     

Peroneal muscular atrophy. Part 2. Nerve biopsy studies

The present study used the nerve pathology, studied by quantitative light microscopy, as the sole basis for classification of peroneal muscular atrophy (PMA). The findings in biopsies of superficial peroneal nerves of 20 patients were compared with normal values obtained from 8 controls. Three homogeneous groups comprising 17 out of 20 patients were clearly identified. The hypertrophic type (7 cases) was characterized by (1) many multilamellated onion bulb formations; (2) extensive loss of MF with both involvement of the largest and smallest fibers; (3) lack of significant cluster formation. The neuronal sensori-motor type (5 cases) was characterized by (1) absence of any OB; (2) elective loss of large MF; (3) abundance of clusters with significant increase of the small MF population. The neuronal motor type (5 cases) showed a virtually normal sensory nerve except for fairly numerous clusters in some cases. Comparing this classification based on histomorphometric grounds, with the electrophysiological data it appears that 14 patients out of 17 would be correctly classified as hypertrophic or neuronal with respect to the motor nerve conduction velocity of the median nerve alone. Three cases were not classified in the previous groups since they differed notably in one or more parameters from the typical cases. A possible intermediate group is discussed.     

Distribution of cisternal blood in patients with acute hydrocephalus after subarachnoid hemorrhage.

The distribution of cisternal blood in relation to the development of acute hydrocephalus was studied in 246 consecutive patients with aneurysmal subarachnoid hemorrhage who were admitted within 72 hours. Patients with evidence on the initial computed tomograph (CT) of subarachnoid hemorrhage caused by other than a ruptured aneurysm and patients with a negative angiography were excluded. Acute hydrocephalus (defined as a bicaudate index, measured on the initial CT or on a repeat CT within 1 week after subarachnoid hemorrhage, exceeding the 95th percentile for age) was found on the initial CT in 50 (20%) of the 246 patients and on a repeat CT in 9 other patients. Ventricular blood was found significantly more often in patients with acute hydrocephalus than in those in whom acute hydrocephalus did not develop (28 of 59 [47%] versus 58 of 187 [31%]; chi 2 = 4.634, p = 0.031). When the analysis was restricted to the 86 patients with ventricular blood, no significant differences were found in the total amount of cisternal blood and in the distribution of cisternal blood between patients with and without hydrocephalus. In contrast, among the 160 patients without ventricular blood, hydrocephalus was associated with a slightly higher total amount of cisternal blood (Wilcoxon's rank sum test, p = 0.023), and significantly more patients with acute hydrocephalus had a higher score in both ambient cisterns than patients without acute hydrocephalus (20 of 31 [65%] versus 41 of 129 [32%]; chi 2 = 10.007, p = 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)     

Hereditary hypertrophic neuropathy in the Trembler mouse: Part 2. Histopathological studies: Electron microscopy

The Trembler mouse suffers from a dominantly inherited hypertrophic neuropathy. Electron microscopy, including a quantitative analysis of myelination was performed on the nerves of Trembler mice from birth to senility and compared with the findings in control mice. Axons in adult Trembler nerves were thinly myelinated and were surrounded by very few myelin lamellae which in turn were often uncompact circumferentially and longitudinally. Schwann cell cytoplasm was copious and had a normal content of organelles. Well-developed “onion-bulb” formations which consisted of thinly myelinated axons surrounded by empty membrane configurations were frequently seen.

The initiation of myelination was studied. The diameter distribution of promyelin fibres of control and Trembler sciatic nerve at ages day 2, 4, and 7 was calculated Myelination in Trembler nerves commenced on axons of larger diameters than controls.

The effectiveness of myelination was studied by relating the number of turns of myelin to the axon area of control and Trembler sciatic nerves from age 2 days to adult mice. At all ages Trembler axons were less well myelinated than controls and the difference was more pronounced with age.

Schwann cell activity was examined by relating the area of the Schwann cell cytoplasm to the area of the axon it invests. The relative amount of Schwann cell cytoplasm decreased progressively in control axons with age and as the axon became better myelinated. By contrast, that of Tremblers did not undergo a similar reduction as the animal matured and the relative amount of Schwann cell cytoplasm was markedly increased in adult Tremblers when compared with controls.

The periodicity of control and Trembler compact myelin was compared. The myelin period of Trembler mouse was significantly greater than that of controls. The defect in Trembler peripheral nerves was considered to be that of dysmyelinogenesis. The Schwann cell was active but ineffective in the synthesis, compaction and maintenance of myelin.     

Parabiotic reinnervation in normal and dystrophic mice. Part 2. Morphological studies.

The technique of parabiotic reinnervation has been used to test directly the neurogenic theory of the aetiology of muscular dystrophy in mice. Dystrophic muscles contain significantly fewer muscle fibres than their normal controls; they also have a much broader spectrum of fibre size because of a much higher proportion of very small fibres and are poorly differentiated into histochemical fibre types. These criteria were used to assess whether there was any amelioration of the dystrophic process in response to the introduction of a normal nerve supply, or whether dystrophic changes were induced in normal muscle reinnervated with a dystrophic nerve. Self-reinnervated normal and dystrophic TA and EDL muscles contained the same numbers of fibres as unoperated controls. The process of parabiosis alone resulted in no changes in normal or dystrophic muscles. In the process of parabiotic reinnervation, the efficiency of the reinnervation process was not affected by the parabiotic state. The parabiotic reinnervation of dystrophic muscle by normal nerve resulted in no significant increase in fibre numbers and the spectrum of fibre sizes was essentially the same as in unoperated dystrophic muscle. The parabiotic reinnervation of normal muscle by dystrophic nerve resulted in a reduction of fibre numbers in only some of the muscles examined. However, the spectrum of fibre diameters remained essentially normal, and the differentiation of the fibres into histochemical fibre types was characteristic of reinnervated normal muscle. There was a marked absence of necrosis or of other histological signs of dystrophy in these muscles. Since there was no positive evidence to show that conversion of normal to dystrophic, or dystrophic to normal muscle occurred under the influence of parabiotic nerve transposition, two alternative conclusions were admissible. Firstly, the influence of dystrophic nerve upon muscle may be operative in fetal or neonatal life and may be irreversible by means of the subsequent introduction of a normal nerve supply. Secondly, the dystrophic state in muscle may be determined by genetic factors independent of nerve supply.     

3-Methoxy-4-hydroxy-phenylglycol sulfate (MOPEG-SO4) in ventricular and cisternal cerebrospinal fluid of dogs.

Cerebrospinal fluid was collected from the lateral ventricles and cisternal space from beagle dogs under light pentobarbital anesthesia. Homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenylglyco-sulfate (MOPEG-SO4) levels in the liquor taken from these two regions were evaluated, and the ventricular-cisternal ratio (V/C) was calculated for each monoamine metabolite. A marked similarity in the V/C ratio of 6:1 for 5-HIAA and 5:1 for MOPEG-SO4, as compared to a much higher V/C ratio of 18:1 for HVA, perhaps reflects the more diffuse distribution of norepinephrine and serotonin, precursor amines, as compared to dopamine in the CNS and also emphasizes the probable existence of an active transport mechanism for the removal of MOPEG-SO4, as has been well documented for 5-HIAA and HVA.     

Dysmyelination in Chow Chow dogs: Further studies in older dogs

Summary The ultrastructure of myelin deficiency in Chow Chow dogs was studied in the spinal cord of a 15-month-old and a 3-year-old animal. It was found that myelination progresses with age in these dogs but is still deficient at the age of 3 years. The findings included axons with thin or uncompacted myelin sheaths, separated from each other by massive astrocytosis, and bizarre myelin formations. Normal numbers of morphologically normal oligodendrocytes were present in the myelin-deficient areas. The disease in these Chow Chow dogs consists of a strongly retarded myelination which is possibly due to a dysfunction or delay in glial maturation.Supported by the Schweizer Nationalfonds grant no. 3.805.79     

Muscle transplantation and regeneration in the dystrophic hamster. Part 2. Histochemical studies

Enzyme histochemical studies have been done on auto- and cross-transplanted normal and dystrophic anterior tibialis muscles of the hamster. The transplants ranged in age from a few hours to well over 300 days.Both degenerating and regenerating muscles are metabolically active. Glycogen and phosphorylase disappear very early from the transplants. Degenerating fibres show uniform dark staining with ATPase at pH 9.4. NADH-TR activity tends to be localised within the fibres and the reaction product is clumped.Regenerating myoblasts and myotubes stain uniformly dark for ATPase at pH 9.4. There is low NADH-TR and phosphorylase activity, the reaction product being frequently clumped. The pentose-phosphate shunt appears to be very active in the early regenerates as the myotubes stain intensely for RNA. Acid phosphatase activity is present in all transplants, being mostly localised in the connective tissue sheath round the muscle fibres.Muscles transplanted for 20 or more days have well-developed end-plates and are fully differentiated into fibre types. A clear-cut checkerboard pattern of light and dark fibres is observed in all transplants with ATPase reaction. Type 1 and 2 fibres can also be distinguished with phosphorylase and PAS. The regenerated fibres show little variation in staining with the NADH-TR reaction.No differences were observed between the regenerates from normal or dystrophic muscle in either the normal or dystrophic host.     

Electrodiagnostic abnormalities in 15 patients with posttraumatic syringomyelia: pre- and postoperative studies

A review of 15 patients with posttraumatic syringomyelia indicates that the most reliable electrodiagnostic criteria for the diagnosis of syrinx are the loss of motor unit numbers with increase in motor unit amplitude and duration nd synchronous firing. Prolongation of F wave latency in a previously stable patient is a useful observation. Return of function and improvement of F wave latencies can occur rapidly following decompression of the syrinx. Forty per cent of the patients studied had concomitant involvement of at least one peripheral nerve as one would expect invoking the double crush hypothesis.     

Studies on the Rett syndrome. Part 2. Polysomnographic and neuroendocrinological studies

The biogenesis of the Rett syndrome (RS) is unknown although there have been several reports suggesting some biochemical defect of the monoaminergic system in CNS. We performed all night polysomnography and neuroendocrinological tests in three cases of RS discovered on a surveillance study in Tokushima. The following results were obtained; 1) dissociation of sleep elements (stage 1-REM, stage 2-REM), 2) no increase in REMs/min with development, 3) abnormal patterns of BMs, TMs of each sleep stage, 4) paradoxical secretion of growth hormone (GH) and excessive secretion of prolactin in TRH provocation test, the absence of sleep enhancement of GH secretion, 5) progressive disfunction of autonomic nervous system during sleep. These results indicated that RS involves the functional disturbances of brain stem and hypothalamic monoaminergic regulatory systems.     

Experimental uremic neuropathy: Part 2. Sodium permeability decrease and inactivation in potential clamped nerve fibers

Potential recordings and potential clamp of isolated myelinated fibers from the sciatic nerve of acutely uremic rats showed a marked decrease in excitability related to a decrease in the specific Na permeability (P_Na) of the nodal membrane. Mean value of the available P_Na in the resting node of the uremic rats was 24% of the P_Na in a control group. This change explained the decreased nerve conduction velocity in the acutely uremic rat. The Na current reversal potential was decreased in some fibers, reflecting an axoplasmic Na accumulation. The decrease in P_Na was to a large extent caused by an increased inactivation, due to a negative shift (about 10 mV) of the steady state inactivation curve along the potential axis. The activation of P_Na was similarly shifted (about 10 mV) to a more negative potential region. Such changes may be caused by elevated intracellular [Ca], suggesting a disturbance in Ca metabolism or an intracellular accumulation of cationic metabolites (which possibly have a similar effect) in rats with acute uremia.     

Spectral analysis of corticomotor evoked potentials in spinal cord injury. Part 2. Chronic studies

Abstract

Corticomotor evoked potentials (CMEPs) have been suggested to accurately reflect neurological function, particularly with regard to the integrity of the spinal cord. However, the utility of these potentials to evaluate gradedchronic injury has received little attention. Frequency analysis has been suggested by the authors to be a method of simplifying interpretation of these complex signals. Ischaemic spinal cord injuries were produced in rabbits causing mild, moderate, or severe neurological deficits. CMEPs were recorded before, during, immediately following, and three days after injury. Alterations in the features of the power spectra reflected the degree of neurological injury. CMEP power spectra may predict neurological outcome and augment currently used electrodiagnostic tests. [Neurol Res 1993; 15: 373-378]