Application of a new rating scale of brain dysfunction to monitoring rehabilitation in 65 patients with severe head injury.

Sixty-five patients with severe head injury sustained in motor vehicle accidents (MVA) are the subject of the prospective investigation. For assessment of results of a particular treatment, planning of long-range management and predicting the outcome in terms of employment or of self-care, it is essential to monitor sequentially the progress of recovery. A comprehensive semiquantitative rating Scale g was developed and its application during repeated examinations demonstrated. The Scale g is open-ended, as it allows physicians and investigators in the health field to produce their own schedules of any disability provided that seven levels of that particular dysfunction are defined according to the principles of Scale g. The progress of recovery in motor deficits, dysarthria, mental impairment, and self-care was assessed using appropriate schedules according to Scale g in 65 inpatients at their first admission to the rehabilitation center and at their discharge. The change was made evident by showing patients' advancement, if present, to the higher functional level. It was estimated at the time of discharge that 23.1% can be expected to return to full-time employment, 38.5% are likely to perform part-time lesser work, 13.8% may be able to perform certain, non remunerative chores at home, 24.6% would not be able to do any work--about one-third of them will permanently require long-care facility.

Changes in brain weights during the span of human life: relation of brain weights to body heights and body weights.

More than 20,000 autopsy reports from several general hospitals were surveyed for the purpose of selecting brains without a pathological lesion that had been weighed in the fresh condition. From this number, 2,773 males and 1,963 females were chosen for whom body weight, body height, and cause of death had been recorded. The data were segregated into 23 age groups ranging from birth to 86+ years and subjected to statistical evaluation. Overall, the brain weights in males were greater than in females by 9.8%. The largest increases in brain weights in both sexes occurred during the first 3 years of life, when the value quadruples over that at birth, while during the subsequent 15 years the brain weight barely quintuples over that at birth. Progressive decline in brain weight begins at about 45 to 50 years of age and reaches its lowest values after age 86 years, by which time the mean brain weight has decreased by about 11% relative to the maximum brain weight attained in young adults (about 19 years of age). Computed regression lines for brain weights versus body heights and body weights and for ratios for brain weights to body heights and weights versus age groups show clearly differential rates of change in brain weights which are less affected by sex.

Content and composition of urinary glycosaminoglycans in the patients with myoclonus epilepsy with and without Lafora bodies.

Content, composition and molecular weight distribution of the urinary glycosaminoglycans (GAG) were determined in five patients with progressive myoclonus epilepsy (PME). In one patient (Family B) this syndrome was associated with cerebral Lafora bodies and in four siblings of Family A, no Lafora bodies were present in brain biopsy. Only one of the five patients had a moderate increase of urinary GAG excretion as expressed by 24-h output or creatinine. The heparan sulfate component of the GAG was moderately increased in two other patients. The molecular weight distribution of the urinary GAG was normal. The results do not support the contention that urinary GAG excretion is abnormal in PME. Among nine lysosomal enzymes in leucocytes, only the activity of alpha-mannosidase was increased 3-fold in the four siblings.

Mucopolysaccharidosis type I, II, IIIA and V. Pathological and biochemical abnormalities in the neural and mesenchymal elements of the brain.

Histochemical and electron microscopic studies of the brains inclusive of the leptomeninges containing large blood vessels from 7 patients with mucopolysaccharidosis (MPS) I, II, IIIA and V showed marked increase in mesenchymal elements and the generalized presence of characteristic lesions around cerebral veins and arteries. The periadventitial space was greatly distended and filled with viscous fluid and numerous mononuclear cells containing large cytoplasmic vacuoles; these cells stained positively for glycosaminoglycans (GAG). In contrast, the neurons showed only a slight increase of GAG over the normal controls but contained an excessive amount of glycolipid-like material. The amount of GAG in the leptomeninges, inclusive of the large blood vessels, was 10.8, 6.5, 4.5 and 2.2 times greater in patients with MPS I, II, V and IIIA respectively, than the mean of unaffected controls. Dermatan sulfate (DS) accounted for most of the GAG increase in MPS I, II and V [mixed excretors of DS and heparan sulfate (HS)], and HS for the GAG increase in MPS IIIA (HS excretor). With the exception of the patient with MPS IIIA, whose GAG content and composition were the same in both the neural and mesenchymal elements, in all the other MPS types the mesenchymal elements contained more GAG, with a preponderance of DS. We conclude that the mesenchymal elements contribute substantially to the increased content of GAG in the brain and its coverings, mostly in the form of dermatan sulfate.

Hyperlipoproteinemia and cerebral strokes.

Determination of lipoprotein patterns and of major plasma lipids was carried out in 171 patients with strokes. Of these, 22 had hyperlipoproteinemia (HLIPR) by paper electrophoresis and by elevation of principal plasma lipids (either cholesterol over 300 mg/100 ml or triglycerides over 200 mg/100 ml or both these components). More than two-thirds of the patients had at least one close relative with elevated blood lipids. Using criteria of the World Health Organization, these patients were classified as follows: 5 had HLIPR type IIa, 8 had HLIPR type IIb, 3 had HLIPR type III and 6 had HLIPR type IV. Phospholipids showed relatively little change from the values of normal controls. The numerical distribution of patients with stroke and HLIPR into the four different types corresponds quite well with the approximate frequency of these types of HLIPR in the general population. Thus, this study does not indicate that the patients with a particular type of HLIPR are at a greater risk to have a stroke than those belonging to other types.

Metabolic fate of phenobarbital. A quantitative study of p-hydroxyphenobarbital elimination in man.

Biotransformation of phenobarbital (PB) to p-hydroxyphenobarbital (PHPB) was studied quantitatively by gas-liquid chromatography in 8 epileptic patients who were receiving an established regimen of antiepileptic drugs including PB. PB and both conjugated and unconjugated PHPB were present in each patient's urine; m-hydroxyphenobarbital (MHPB) was not detected despite an assay sensitivity of 0.25 mug/ml. Incubation of the urine with beta-glucuronidase, but not with arylsulfatase, liberated PHPB which was, therefore, presumed to be conjugated with glucuronic acid. In general, the patients' urine contained more PB than total PHPB. Recovery of the patients' total daily dose of PB ranged from 24 to 77% (mean, 42%). After receiving a single iv dose of PB, PB and both conjugated and unconjugated PHPB were found in a normal volunteer's urine throughout a 16-day collection period; 30% of the dose was recovered. PB excretion was proportional to urine volume in the volunteer and in two additional patients who were made to vary their daily fluid intake. PHPB was not detected in the cerebrospinal fluid of 10 patients receiving PB. Neither PB, PHPB, nor MHPB were detected in the feces of four patients. These results suggest that metabolites other than PHPB or MHPB may be important in the elimination of PB in man.

Familial cerebellar degeneration with slow eye-movements, mental deterioration and incidental nevus of ota (oculo-dermal melanocytosis).

Four members of a family with an autosomal dominant form of cerebellar degeneration all had slow eye-movements, i.e. slow pursuit with absence of both nystagmus and rapid saccadic movements. Three showed progressive mental deterioration. One patient had nevus of Ota (oculodermal melanocytosis) and a history of grand mal epilepsy. In these four patients the symptoms first occurred between the ages of 10 and 31 years--the onset apparently appearing earlier with successive generations. Current studies implicate a brain-stem lesion of the paramedian pontine reticular formation in the pathogenesis of the oculomotor abnormality. The possibility of a neurocutaneous syndrome, specifically a 'melanophakomatosis', in the patient with seizures and nevus of Ota is discussed; however, absence of these findings in other affected relatives makes a fortuitous association more probable. The literature on nevus of Ota associated with neurological disease is considered.

Mucopolysaccharidosis type V. (Scheie syndrome). A postmortem study by multidisciplinary techniques with emphasis on the brain.

Multidisciplinary studies were conducted on the brain and other tissues of patients who died with the antemortem diagnosis of mucopolysaccharidosis (MPS) of one of the following types; type V, Scheie disease (MPS-V); type I, Hurler disease (MPS-I): and type II, Hunter disease (MPS-II). The principal new finding in the brain of the patient with MPS-V is the presence of lesions in the periadventitial mesenchymal tissue of the white matter, similar to those of MPS-I, while the nerve cells in MPS-V are histologically normal, in contradistinction to MPS-I, in which the neuronal abnormality is severe. Electron microscopical studies of the brain in MPS-I demonstrated numerous complex membranous inclusions in the neurons, whereas the neurons in MPS-V contained only a small number of lipofuscin-like inclusions and typical lipofuscin granules. There was a threefold increase of glycosaminoglycans (GAG) in the brain of MPS-I, but only a slight increase in the MPS-V; GAG in the liver and spleen of all patients was noticeably increased. alpha-L-iduronidase activity was not detectable in the brain and liver of patients with MPS-I and MPS-V, thus suggesting a similar enzymatic defect.

Effects of different dosages of anticonvulsant drugs on mental performance in patients with chronic epilepsy.

Fifteen epileptic patients had their dose of anticonvulsant drugs changed twice, each time by 30-50 per cent of the initial medication. Before the dose change, the patients were given six especially adapted mental performance tests, which were designed to measure vigilance, reaction time and certain aspects of memory. Serum drug levels were also monitored. The main results include assessment of effects of drugs on mental performance and evaluation of the psychological tests used. (1) Vigilance and reaction time test were the most useful in evaluation of effects of various doses of the medication; the memory tasks showed similar, but less definite, trends; and rote calculation and block design were of no particular value in this study. (2) On the tests for vigilance and reaction time, the greatest number of patients performed best on the lowest dose of their medication, the respective percentages being 45.8 and 56. By comparison, fewest patients performed best on their highest dose, the percentages being 16.7 for vigilance and 12.5 for reaction time; while the percentages on medium dose were 37.5 and 31.2 on the respective tests. (3) Use of well-standardized, yet simplified, mental performance tests in combination with changes in the dosage of medication can help in reaching a compromise between acceptable seizure control and avoidance of excessive slowing of mental activity.

Kinky hair disease. Study of copper metabolism with use of 67Cu.

Metabolism of labeled Cu (67Cu) was studied in three patients with kinky hair disease (KHD). Labeled Cu was administered first intravenously and, later, orally. We determined oral absorption, excretion, and internal kinetics of this metal. Patients with KHD absorbed 11% to 13% of Cu given orally, compared to 46% by unaffected controls. Total excretion of Cu given intravenously during the first seven days after administration was greatly reduced in patients with KHD. The biological half-life of 67Cu in patients with KHD was increased by a factor of 2 to 3 over the normal control. Most of the labeled Cu was retained by the patient's liver, while in the control subject there was more rapid movement to the Cu to circulation (ceruloplasmin). Red blood cells of patients with KHD incorporated orally administered Cu preferentially, which was sufficient to prevent anemia.

Chemical definition of the mucopolysaccharidoses.

Glycosaminoglycans were isolated from the urines of 46 patients with mucopolysaccharidosis; 11 with Type I (Hurler), 8 with Type II (Hunter), 16 with Type III (Sanfilippo A and B), 9 with Type V (Scheie), one with Type VI (Marateaux-Lamy), and one unclassified. All 46 patients excreted in their urine excessive amounts of dermatan sulfate, heparan sulfate or both. In addition, patients of certain types excreted excessive amounts of chondroitin sulfates A and/or C. There is a trend in each type of the disease towards the same carbazole/orcinol ratio, glucosamine/galactosamine ratio and glycosaminoglycan composition. Molecular weight distribution of the urinary glycosaminoglycans by gel filtration from Sephadex G-200 is characteristic for each different type of mucopolysaccharidosis and is distinguished from normal controls and patients without mucopolysaccharidosis. Preparation of elution diagrams from Sephadex G-200 allows an estimation of the composition of the glycosamino-glycans. Practically all heparan sulfate and a sizable part of dermatan sulfate from the urinary glycosaminoglycans of all these patients have been highly degraded. In all the patients in which the specific enzyme defect was demonstrated, the assignment of the type of mucopolysaccharidosis, on the basis of the elution diagrams, was correct. Patients with mucopolysaccharidosis Type V displayed two conspicuously different types of elution patterns, suggesting heterogeneity. Indeed, only a portion of these patients showed alpha-L- iduronidase deficiency. Carriers had normal urinary glycosaminoglycan output and composition and exhibited normal elution diagrams.