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SUMMARY The clinical features and autopsy findings are reported in a man of 23 years with gargoylism. Hydrocephalus was demonstrated by pneumography and successfully treated by a ventriculo-atrial shunt. Throughout his life span, the patient was of average intelligence; there was no evidence of dementia. The leptomeninges were thickened, and the perivascular spaces within the brain were enlarged. No storage material was found in the nerve cells. The clinical and pathological findings are discussed in relation to the basic metabolic abnormalities. We postulate that mental retardation in gargoylism is associated with neuronal storage of glycolipid within the brain. Normal intelligence is to be expected in those patients with gargoylism who do not have neuronal storage. RESUME Les bases neuro-pathologiques de la sub-normalite mentale dans le gargoylisme (syndrome de Hunter-Hwler) Les auteurs exposent les caracteristiques cliniques et les resultats de Fautopsie d'un cas de gargoylisme chez un homme âge de 23 ans. L'hydrocephalie a ete mise en evidence par pneumographie et traitee avec succes au moyen d'une derivation atrio-ventriculaire. Pendant la duree de sa vie le patient etait d'une intelligence moyenne; il n'y avait aucun signe de demence. Les leptomeninges etaient epaissies et les espaces perivasculaires a l'interieur du cerveau etaient agrandis, aucune substance de reserve n'a ete decelee dans les cellules nerveuses. Les donnees cliniques et pathologiques sont discutees en function des anomalies meta-boliques basiques. Nous emettons le postulat suivant: le retard mental dans le gargoylisme est associe au depot de glycolipide en reserve dans les neurones a l'interieur du cerveau. On peut s'attendre a trouver une intelligence normale chez les patients atteints de gargoylisme qui n'ont pas de depot dans les neurones. ZUSAMMENFASSUNG Die neuropathologische Basis der geistigen Zuruckgebliebenheit bei Gargoylismus (Hunter-Hurler Syndrom) Es wird Bericht erstattet uber die klinischen Merkmale und Autopsiebefunde bei einem 23 jahrigen, mit Gargoylismus behafteten Mann. Wasserkopf wurde duch Pneumographie bewiesen und erfolgreich behandelt mit einer ventriculo-atrialen Seitenanknupfung. Der Patient war durchweg in seiner Lebensspanne von durchnittlicher Intelligenz, es lag kein Beweis von Demenz vor. Die weichen Spinnwebehaute (Leptominges) waren verdickt und die perivaskularen Zwischenraume innerhalb des Gehirns waren vergrossert. Es wurde kein aufgespeichertes Material in den Nervenzellen gefunden. Die klinischen und pathologischen Befunde in Beziehung zu den grundlegenden meta-bolischen Abnormalitaten werden besprochen. Wir setzen als gegeben voraus, dass geistige Zuruckgebliebenheit bei Gargoylismus mit neuronaler Speicherung von Glycolipid im Gehirn verbunden ist. Es wird normal elntelligenz von diesen, mit Gargoylismus behafteten Patienten erwartet, die keine neuronale Speicherung haben. RESUMEN La subnormalidad mental en el sindrome de Hurler (lipocondrodistrofia). Una causa bioquimica sugerida. Se describen el cuadro clinico y los resultados de una autopsia en el caso de un hombre de 23 anos que padecia del sindrome de Hurler. Se hallo hidrocefalia por medio de una neumografia, la cual fue tratada con buen exito por una derivation ventriculo-auricular. Durante su vida entera, el paciente era de inteligencia media; y no habian ningunas pruebas de demencia. Las leptomeninges se habian espesado y los espacios perivasculares dentro del cerebro se habian engrandecido. No se encontro ninguna materia acumulada en las celulas nerviosas. Se discuten los descubrimientos clinicos y patologicos con relacion a las anormalidades metabolicas fundamentales. Sugerimos que un atraso mental en la enfermedad de Hurler se asocia con una acumulacion neuronal de glicolipina dentro del cerebro. Hay que esperar que se hallara una inteligencia normal en los pacientes que padecen de la enfermedad de Hurler y que no tienen acumulaciones neuronales.

Acute bacterial meningitis can result in structural damage to the nervous system with associated functional derangements. Neurologic abnormalities can be transient, although some sequelae, including lasting impairment in cognition and behavior, may be permanent.1,2In this brief report, we present the results of psychometric testing of patients conducted over a 5-year period in our prospective study of acute bacterial meningitis begun in 1973.

One hundred thirteen infants, aged 1 to 18 months, were screened systematically and serially using transillumination for the presence of subdural effusion during acute bacterial meningitis due to Haemophilus influenzae type b, Streptococcus pneumoniae, or Neisseria meningitidis. Effusion developed in 44 (39%) of the patients during the course of treatment. Young age, rapid onset of illness, low peripheral white blood cell count, and high cerebrospinal fluid levels of protein and bacterial antigen were associated with a higher likelihood of developing effusion. Although patients with effusion were more likely to have neurologic abnormalities both at the time of admission and at completion of therapy, and were more likely to have seizures during the course of treatment, there was no greater incidence of seizures, hearing loss, neurologic deficits, or developmental delay on long-term follow-up (median follow-up interval 5.5 years) in patients with effusion. Specific invasive therapy is not indicated in infants with meningitis and subdural effusion who are otherwise improving.

Between 1975 and 1990, a total of 34 patients with water intoxication were treated at St Louis (Mo) Children's Hospital, 24 of these in the last 3 years, indicating a marked increase in incidence of this previously rare condition. Thirty-one were infants living in poverty who ingested excessive amounts of water offered at home by their caretakers. Exhaustion of the supply of infant formula was the most common reason given for this substitution. Infants were treated by a single infusion of hypertonic saline or a slow infusion of isotonic saline. Central pontine myelinolysis was not observed as a complication of hypertonic saline therapy. Modification of the Special Supplemental Food Program for Women, Infants, and Children to provide sufficient formula for the growing infant and better education of mothers as to the hazards of excessive water ingestion might reduce the incidence of this preventable and life-threatening condition.

Although the mortality rate among children with bacterial meningitis has decreased dramatically in recent decades, some patients are left with neurologic sequelae. It has not been clearly established which features of the acute illness predict the chronic neurologic sequelae, including late seizures or epilepsy.We followed 185 infants and children prospectively during and after acute bacterial meningitis. The mean duration of follow-up was 8.9 years (range, 0.1 to 15.5). During the first six years standard neurologic examinations were performed; telephone interviews were conducted thereafter.One month after meningitis, 69 children (37 percent) had neurologic abnormalities. Many of these signs resolved within a year, leaving only 26 children (14 percent) with persistent deficits: 18 (10 percent) had only sensorineural hearing loss, and 8 (4 percent) had multiple neurologic deficits. Thirteen children (7 percent) had one or more late seizures not associated with fever. The presence of persistent neurologic deficits indicative of cerebral injury was the only independent predictor of late afebrile seizures (P less than 0.001).After bacterial meningitis only children with permanent neurologic deficits are at high risk for epilepsy. Those with normal examinations after the acute illness have an excellent change of escaping serious neurologic sequelae, including epilepsy.

In Reply .—As reflected in our title, we believe the incidence of oral water intoxication is far greater than the medical literature suggests and that it increased rapidly in the 1980s. The patients described by Furth and Oski added to those of Medani 1 increase to 58 the number of affected infants in one city, appearing to support our impression as to the increasing occurrence of this condition. We speculated that the clustering at age 4 months occurs because that is when the infants "outgrow" the allotment from the Women, Infants, and Children program (one can of formula per infant per day from birth to age 365 days). Furth and Oski found fewer mothers who said that they had exhausted their supply of formula, leading these authors to conclude that multiple causes of this problem exist. All three studies are retrospective reviews, so the maternal motivation for offering water remains uncertain.

Hypernatremic dehydration was induced in rabbits during a 3- to 5-day period resulting in mean plasma sodium concentrations of 187 meq/liter. The animals were then rehydrated during a 4-h period by intravenous administration of a 2.5% glucose or fructose solution. The water content of four regions of brain sample showed a significant (P less than 0.05) increase in brain water content above normal in the rehydrated groups. Brain water content was significantly (P less than 0.01) greater in those animals with seizures compared with those without seizures, suggesting the importance of water intoxication in the pathogenesis of seizure activity. Changes in muscle Na, K, Cl, and water content were not similar to those of brain, indicating that muscle content of these substances was not an accurate reflection of the brain content specific time. The incidence of seizures was significantly (P less than 0.05) greater when glucose solution was used for rehydration (49%) compared with the use of fructose solution (25%). The mechanism(s) by which fructose resulted in a lower incidence of seizures is not known. The frequency of seizure activity was directly proportional to the rate of administration of intravenous solutions utilized to correct hypernatremia. In addition, the specific carbohydrate of the solution appeared to play an important role in the pathophysiology of the development of seizures.

This article discusses the management of seizure disorders, stressing selected aspects including (1) the pharmacology of drugs used in the control of seizures, especially the usefulness of measuring concentrations of anticonvulsants in blood in guiding therapy; (2) the treatment of prolonged seizures, particularly status epilepticus, in infants and children; (3) the use of the ketogenic diet as an adjunct in the therapy of epilepsy; and (4) the place of surgical treatment in the control of seizures resistant to medical management.

As part of a prospective study of acute bacterial meningitis in children, we studied for five years the hearing of 185 infants and children who had acute bacterial meningitis when they were more than one month of age. Nineteen (10.3 per cent) of the patients had persistent bilateral or unilateral sensorineural hearing loss. The incidence of hearing loss as determined by electric-response audiometry and conventional tests was 31 per cent with Streptococcus pneumoniae, 10.5 per cent with Neisseria meningitidis, and 6 per cent with Hemophilus influenzae infections. Transient conductive hearing impairment was found in 16 per cent of the sample, but in no case was there apparent improvement in a sensorineural deficit over time. The site of disease resulting in impaired hearing cannot be stated with certainty, but involvement of the inner ear or auditory nerve was suspected. The number of days of illness (symptoms) before hospitalization and institution of antibacterial treatment was not correlated with the development of sensorineural deafness.

Hypertonicity of the body fluids was induced in rabbits by the intravenous infusion of different hypertonic solutions (NaCl. NaCl plus NaHCO3, sucrose, mannitol and urea). The results obtained in this study indicate the following. There is no significant correlation between the clinical syndrome or death and values for total body water, total body solutes, total extracellular or intracellular volume, or concentration of sodium or chloride in the plasma. The clinical manifestations and death can occur in the absence of in tracranial hemorrhage. Hypertonicity, by creating an osmotic gradient between extracellular fluid and brain, is the important factor in producing the characteristic clinical syndrome and death, but is not the immediate cause of these abnormalities. The osmolality necessary to produce these alterations was greater in animals infused with urea. Hypertonicity produces these alterations by decreasing water and increasing ion concentration in the brain. The resulting functional impairment of neurones accounts for the clinical and electroencephalographic abnormalities. The increased values of sodium and chloride in the brain reflect an impairment of function of either brain cells, "blood-brain barrier," or both. Acidosis, hyperkalemia and hyerphosphatemia ensue as a result of hypertonicity. Unless death is imminent, all of the abnormalities described are reversible.

As new and elaborate tools for medical diagnosis are developed, time-honored and simpler methods are often neglected. This we believe to be true of the technique of transillumination, as applied to the diagnosis of intracranial pathology. Illumination of the cranial cavity by sunlight and candle was described as early as 1831 by Richard Bright 1 (Fig. 1). In 1910, Strasburger 2 commented on its use in evaluation of the hydrocephalic child, and during the early part of this century von Bokay 3 developed the technique of transillumination to a remarkable degree. More recently, there has been renewed interest in this technique, but the majority of physicians still employ it only rarely and are unaware of its considerable value in neurologic diagnosis. During the past few years, the routine use of transillumination in the examination of infants and children with neurologic disease on the wards of the Children's Service of the

Hypertonicity of body fluids was induced in 23 rabbits by the intravenous injection of solutions of sodium chloride, sodium chloride and bicarbonate, sucrose, or urea at concentrations of about 2,000 mOsm/l. The results obtained suggest that (1) hypertonicity of body fluids can cause disturbances in cellular metabolism, resulting in the formation and release of large quantities of hydrogen ion and the development of severe extracellular metabolic acidosis; (2) with restoration of osmolality toward normal by rehydration, the acidosis is improved; and (3) there is no correlation between the values for plasma pH and the values for sodium and chlorides in plasma, total body water, extracellular and intracellular water, and blood volume.

Relative nutritional deprivation was produced in groups of 16 to 21 newborn rats who were all nursed by one dam (deprived group) and compared with control litters containing 10 or less animals. Both groups were weaned at 21 days and thereafter allowed an unlimited supply of food. There was diminished somatic growth in all of the deprived group and, at 2 and 3 weeks, the weight of many of the deprived animals was approximately one-half that of the controls. Brain weight, total brain lipids, cholesterol, and phospholipids were reduced to approximately 80% of the control. Brain cerebrosides were affected to a greater extent than the other lipids, being only 50% of the control values. Histological sections showed less myelin. At 6 weeks, following 3 weeks of ad lib. food intake, the body weight, brain weight, and concentrations of the brain lipids of the initially deprived animals were essentially equal to those in the control animals.

IN 1933 Dawson1 reported the finding of intranuclear inclusions within nerve and glial cells of the central nervous system in a fatal case of encephalitis in man. Since then, no less than 33 additional fatal cases have been recorded in the liter-ture.2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 Although most authors agree that the pathological findings suggest a viral etiology, this was established in only 4 of these cases. In each the patient had an acute illness, and the virus of herpes simplex was recovered from the brain at aut-psy.12 13 14 15 The illness in most of the remaining cases was subacute or chronic, and the pattern of . . .

Herpes simplex virus was instilled in the conjunctival sac of six rabbits; four of these animals developed clinical evidence of encephalitis within 6–10 days and died of their disease within 1–4 days. In these animals EEG tracings showed the development of seizure discharges occurring on a background of irregular slow waves. These EEG changes appeared before definite clinical evidence of encephalitis in every animal. In the two animals which survived, no such changes were seen over a 6 week period following inoculation of virus.

The present study describes the results of rehydration of rabbits rendered chronically hypernatremic by the administration of one molar sodium chloride solution by nasogastric tube for 23½ to 5 days. When these animals were rehydrated intravenously over a 4-hour period with 2.5% dextrose in water, returning the plasma sodium level to normal, 55% of them developed focal or generalized convulsions. The mean water content of brain tissue of the group of animals who had seizures was significantly greater than that of a normal group of animals and comparable to that found in a water-intoxicated group of animals. This elevation of water content could be accounted for by both an elevated content of potassium and chloride in the brain. The potassium content of the brain was higher in the rehydrated group of animals without than those with seizures. Ways by which the observed changes may be related to the development of seizures are discussed.

THE 5 children described below had an illness characterized by excessively rapid growth, acromegalic features and a nonprogressive cerebral disorder with mental retardation. The pattern of clinical...

Seven patients aged six to 16 years, had transient total blindness following seemingly trivial blunt head trauma. The blindness persisted for a few minutes to three to four hours. With one exception, there were no other ocular abnormalities. Bilateral occipital slowing was noted on the electroencephalogram in the early post-traumatic period. Restlessness and agitation were prominent during the period of blindness, but behavior reverted to normal with the return of vision. Recovery was complete in every case. The type of trauma frequently involving the parieto-occipital regions, the prominence of posterior slowing on the electroencephalogram and the absence of associated ocular abnormalities when the blindness was complete suggest some type of temporary cerebral dysfunction, although the precise mechanism is obscure.

In thirty-two rabbits epidural electrodes were placed and in ten of these animals concentric depth electrodes were placed stereotactically. All animals with both epidural and stereotactically placed electrode; were rehydrated with intravenous 2.5% dextrove in water over a four-hour period. Animals with just epidural electrodes had normal tonicity restored by intravenous 2.5% dextrose administered over six or eight hours or by the ad libitum oral intake of tap water. The electrical cortical activity was monitored at 15 minute intervals throughout rehydration and for an additional four-hour observation period. In animals rehydrated over a four-hour period seizures were most prominent during the third and fourth hour of rehydration and the first hour of the observation period. Slowing of the electrical actisity and development of spikes occurred during this same period of time in some animals without as well is some with clinical seizures.

NOWHERE have the effects of the introduction of antimicrobial agents during the past two decades been more dramatically exhibited than in bacterial meningitis. Whereas formerly untreated pyogenic meningitis was fatal with rare exceptions,1 in the antibiotic era there has been a gratifying lowering of the mortality rate.2 3 4 5 But during the past eight to ten years, there has been no outstanding change in the mortality rate in the principal types of bacterial meningitis. Although it might appear that a plateau has been reached in the treatment of this disease, we are unwilling to accept this view without exploring fully the basis . . .

Myotonic dystrophy is more often symptomatic in infancy and early childhood than previously supposed, seven definite and two possible cases having come to our attention during a single year. In all but one case the disease was present, though unrecognized, in one or more members of preceding generations. At least three patterns of expression of the disease are suggested. (1) The most common clinical syndrome (five cases) begins at birth or in early infancy with difficulty in nursing, attributable to bilateral facial weakness. Generalized myopathic weakness and hypotonia and variable degrees of retarded motor development are encountered during infancy. In one case there was no difficulty with bulbar musculature and only the limb muscles were involved. No evidence of a progressive loss of motor function has been observed during early childhood, but the pattern of greater proximal than distal weakness of extremities appears to become reversed gradually until the tyical adult distribution of weakness and atrophy is seen. The less common clinical syndromes, which include the two possible cases of myotonic dystrophy, are: (2) almost pure myotonia, symptomatic from early infancy (one case) or evident only on electromyography (one case) and (3) isolated congenital ptosis (one case). Percussion myotonia or myotonia of grasp or both is usually present if looked for. Electromyographic evidence of myotonia has been found in every case and was of great help in establishing the diagnosis. Myopathic changes were identified in three of the five available muscle biopsies. Mental defect was an associated finding in onethird of the cases in the present series.

The author states that the purpose of the investigation upon which this small monograph is based was to search for the endogenous predisposition to postvaccinial encephalitis in an attempt to bring the problem closer to a solution. Unfortunately, from the data presented this reviewer could not be convinced that an endogenous predisposition to this disease had been discovered or that the problem was any closer to a solution. The first 2 chapters of the monograph are devoted to an interesting historical survey of smallpox, vaccination, and the political difficulties encountered in relation to the latter in the Netherlands. Despite vigorous opposition from certain religious groups, the first law requiring vaccination of pupils and teachers in elementary schools, volunteers in charitable institutions, prisoners, and military personnel was passed in 1872. Following publication of Van Bouwdijk Bastiaanse's cases of postvaccinial encephalitis more than a quarter of a century ago, concern arose over

Bacterial meningitis remains a very significant problem, having increased in frequency during the past several decades. This discussion highlights current concepts of pathophysiology, diagnosis, and treatment. In addition, specific attention is drawn to various sequelae of meningitis, and to certain clinical and laboratory findings which may be of value in predicting which sequelae will occur.

Summary: Hypernatremic dehydration (mean plasma sodium, 184 mEq/ L) was produced over a 3-5 d period in 71 rabbits. The dehydrated animals were divided into groups and rehydrated by intravenous (4, 6, and 8 h duration) or oral (4 and 24 h duration) solutions in amounts calculated to return plasma Na to 140 mEq/ L. Plasma was obtained serially from each animal for electrolyte and osmolality determinations during dehydration and rehydration. Samples of brain hemisphere and cortex were obtained for chemical analysis from every animal immediately after death. The incidence of seizures was significantly less (P < 0.025) in rabbits rehydrated orally when compared with rabbits rehydrated by the intravenous route. Brain water content was significantly greater in rabbits rehydrated intravenously when compared with normal rabbits and rabbits rehydrated orally. In addition, the amount of brain water was greater in rabbits with seizures when compared with those which did not have seizure manifestations.The mechanism underlying the significant reduction in seizures when the animals were rehydrated orally may relate to an integration of drinking behavior with rehydration status. Administration of oral fluids may provide an effective method of therapy for some patients with hypernatremic dehydration.

✓ The clinical course and pneumoencephalographic findings of 14 patients with the associated anomalies of craniosynostosis and hydrocephalus are reviewed. Postmortem examination in two cases, one of which had aqueductal stenosis, confirmed the presence of hydrocephalus. Eight of the 14 had associated anomalies of the extremities consistent with the diagnosis of Apert's syndrome and six patients had dull to normal intelligence. Various types of sutural involvement were present including isolated closure of the sagittal suture. The hydrocephalus, which appears to be an associated anomaly rather than a direct consequence of the craniosynostosis, is most often communicating, but stenosis and atresia of the aqueduct may be present. No single pathogenetic mechanism seems responsible for the abnormal ventricular enlargement, but when the dilation becomes progressive, surgical intervention may be indicated.

Introduction The manifestations of water intoxication in man are primarily neurological and consist principally of reduction in awareness and responsiveness, seizures, and increased intracranial pressure. The condition is being recognized more frequently in the clinic but is not often brought to the attention of the neurologist. Moreover, many aspects of its pathogenesis and therapy remain obscure. These facts have stimulated us to review the clinical aspects of this disorder in a recent publication 1 and to report here on physiological and chemical observations in experimentally induced and treated water intoxication in rabbits. Material and Methods Young male rabbits of the New Zealand strain weighing 2.2-4.3 kg. were used. They were removed from their individual cages without special preparation at about 7:00 A.M., weighed and anesthetized with intravenous pentobarbital sodium, 30 mg. per kilogram. The ears, scalp, and right femoral areas were then depilated with electric clippers. A No. 6-F, multieyed

THE ASSOCIATION of encephalitis and chorioretinitis in a young infant brings to mind a number of etiological considerations, prominent among them being syphilis, toxoplasmosis, and cytomegalic inclusion disease. 1,2 Yet, experience teaches that it is often impossible to incriminate these or any other agent, so that the etiology remains obscure. 3 In the case to be presented, the cerebrum and the retinae were devastated within a few weeks by an inflammatory disease process. Although no infective agent was recovered from various body fluids during life, herpes simplex complement fixing antibodies in the infant's blood rose significantly. It is because of this finding and that of the closely documented evolution of a necrotizing encephalitis and chorioretinitis in a young infant that this case is reported. Report of Case A 25-day-old white girl was admitted to the Massachusetts General Hospital because of focal convulsions. She remained in the hospital until four weeks

The concept that the choroid plexus might participate in the absorption of cerebrospinal fluid is not a new one. Frederick Foley,1 in 1921, postulated the resorption of cerebrospinal fluid by the c...

While the article by De Vivo and Dodge1 on the diagnosis and management of head injury was an excellent review of this problem, I would like to take issue with their statements concerning the physical rehabilitation of the traumatized child. Though responsible professionals in the field of pediatric rehabilitation share the authors' concern about the inadequate documentation of the results claimed by proponents of "elaborate and time-consuming programs of physiotherapy" applied to post-traumatic brain damaged patients, the authors' proposed approach utilizing only range of motion exercizes "to minimize contractures and maintain muscle tone and strength" is inadequate.