John M. Freeman

Efficacy of the Ketogenic Diet for Intractable Seizure Disorders: Review of 58 Cases

Summary: The ketogenic diet was developed in the 1920s as a treatment for intractable childhood seizures when few antiepileptic drugs (AEDs) were available. There are still children whose seizures are refractory even to modern therapy, but use of the ketogenic diet appears to be waning. At Johns Hopkins, we continue to believe that the diet is very effective and well accepted by patients and families. To reevaluate our opinion of the efficacy and acceptability of this form of therapy in patients cared for in the 1980s with the newer AEDs, we analyzed the records of 58 consecutive patients who had been started on the diet. Before using the diet, 80% of the patients had multiple seizure types and 88% were treated with multiple AEDs; these children were among our most intractable patients. Despite this, seizure control improved in 67% of patients with the ketogenic diet, and actuarial analysis indicated that 75% of these improved patients continued the diet for at least 18 months. Sixty‐four percent had AEDs reduced, 36% became more alert, and 23% had improved behavior. The improvement in these patients with intractable seizures and the length of time that families maintained the regimen indicate that the ketogenic diet continues to have a very useful therapeutic role in selected patients and their families.

The paralysis associated with myelomeningocele: clinical and experimental data implicating a preventable spinal cord injury.

Paralysis seen in children with myelomeningocele has been attributed to congenital myelodysplasia. We suspected that paralysis may be due in part to a spinal cord injury caused by exposure of the neural tube to the amniotic fluid. This hypothesis was tested using a fetal rat model of surgically created dysraphism. Each pup from the experimental group of rats in which the spinal cord was intentionally exposed to the amniotic fluid was born with severe deformity and weakness of the hind limbs and tail. Control fetal rats, subjected to the same procedure without directly exposing the spinal cord to the intrauterine environment, were normal at birth. Histological studies of the exposed spinal cord revealed extensive erosion and necrosis, findings similar to those described in children with myelomeningocele. We therefore propose a two-hit hypothesis to explain the paralysis seen in children with myelomeningocele: congenital myelodysplasia complicated by an intrauterine spinal cord injury. Intrauterine protection of the exposed spinal cord might prevent some or all of the paralysis. The possible implications of these findings for the future treatment of myelomeningocele are discussed.

Effects of ketogenic diet on development and behavior: preliminary report of a prospective study.

The ketogenic diet is increasingly used for the management of difficult-to-control seizures in children. Here, we describe the first prospective study of the effects of the diet on development, behavior, and parenting stress. Participants were 65 children (36 males, 29 females) with intractable seizures, ages 18 months to 14 years 6 months, enrolled in a prospective study at the Johns Hopkins Hospital, Baltimore, MD, USA, to study the diets efficacy. Children were assessed before diet initiation and at 1-year follow-up. At follow-up, 52% (34 of 65) children remained on the diet. Mean seizure frequency decreased from 25 per day before diet initiation to less than two per day 1 year later. At follow-up, mean developmental quotient showed statistically significant improvement (p<0.05), with significant behavioral improvements in attention and social functioning. Parental stress was essentially unchanged. No baseline factor examined predicted diet adherence, and the primary reason for diet discontinuation was insufficient seizure control. These preliminary results support prior anecdotal reports of the beneficial effects of the diet on cognition and behavior.

Intrauterine repair of experimental surgically created dysraphism

The paralysis seen in children with myelomeningocele has been attributed to congenital myelodysplasia. Clinical and pathological data, however, suggest that the paralysis may be due in part to a spinal cord injury caused by exposure of the neural tube to the intrauterine environment. This possibility has been supported by experimental data obtained using a fetal rat model of surgically created dysraphism. In this paper, we report the results of intrauterine treatment of experimental dysraphism in the fetal rat and the fetal pig. These studies confirm our earlier findings and suggest that both physical trauma and toxic injury may contribute to the spinal cord injury.

Progressive Unilateral Encephalopathy of Childhood (Rasmussen's Syndrome): A Reappraisal

Summary: Twelve children with Rasmussens encephalitis underwent hemispherectomy and have been followed for an average of 9.15 years. Our decision‐making process leads to early, rather than late operation. Because hemiplegia is inevitable with or without operation, earlier operation may allow such children to resume a more normal life. We postulate that earlier operation may prevent some of the intellectual decline that accompanies the continued seizures and their treatment. In view of the variable pathologic findings and lack of evidence of a viral etiology, we suggest either use of the term “progressive unilateral encephalopathy of childhood” or “Rasmussens syndrome” in recognition of its heritage.

Biofeedback Treatment of Fecal Incontinence in Patients with Myelomeningocele

Approximately six hours of biofeedback training was given to eight fecally incontinent children with myelomeningocele in order to establish bowel control. Their ages ranged from five to 15 years. The patients were shown a polygraph tracing of the external anal sphincter while they were being encouraged voluntarily to contract the sphincter when the rectum was distended with progressively larger volumes of air in a balloon. Seven of the eight patients showed normal sensation for rectal distension.

Informed consent for a prescription drug: Impact of disclosed information on patient understanding and medical outcomes

Abstract Based on the two legal standards of informed consent currently in use, the Medical Practice Standard and the Reasonable Person Standard, two disclosures containing information about the risks and benefits of the anticonvulsant, Carbamazepine, were empirically derived. One of these two disclosures was randomly given to a sample of 39 seizure patients and the parents of pediatric seizure patients prescribed this drug. Subjects were interviewed either immediately after disclosure and at followup, or at followup only. The results provide no evidence for the hypothesized negative effects — anxiety, treatment refusal, reduced compliance and increased side effects — of providing patients with extensive disclosures about prescription drugs.

Neonatal seizures—diagnosis and management

Summary Neonatal seizures may take many forms, with tonic-clonic movement being the least common type. Treatable causes of seizures should be evaluated before standard anticonvulsants are used. Though the mortality rate is high, survivors have a significant chance of being normal.

Hemispherectomy sustained before adulthood does not cause persistent hemispatial neglect

INTRODUCTIONnHemispatial neglect has been well established in adults following acute ischemic stroke, but has rarely been investigated in children and young adults following brain injury. It is known that young brains have a tremendous potential for reorganization; however, there is controversy as to whether functions are assumed by the opposite hemisphere, or perilesional areas in the same hemisphere. Patients with intractable epilepsy who undergo hemispherectomy for treatment are missing the entire cortex on one side following surgery. In these patients, only the opposite hemisphere is available to assume function. Therefore, they provide the unique opportunity to determine in what cases the left or right hemisphere can take over the spatial attention functions of the opposite hemisphere following damage. The objective of this study was to determine the incidence and types of hemispatial neglect in children and young adults following both right- and left-sided hemispherectomy; which types of spatial attention functions can be assumed by the opposite hemisphere; and whether factors like their age at time of surgery, handedness, or gender influence recovery.nnnMETHODSnThirty-two children and young adults who had previously undergone hemispherectomy were administered two tests to evaluate for two types of hemispatial neglect: a gap detection test and a line cancellation test. Egocentric neglect was defined as significantly more omissions of targets on the contralesional versus ipsilesional side of the page (by chi square analysis; p<.05). Allocentric neglect was defined as significantly more errors in detecting contralesional versus ipsilesional gaps in circles.nnnRESULTSnOnly one of the patients displayed statistically significant hemispatial egocentric neglect on the line cancellation test, and none of the patients displayed statistically significant egocentric or allocentric neglect on the gap detection test.nnnCONCLUSIONSnThese results imply that reorganization to the contralateral hemisphere occurs peri-hemispherectomy, as there are no perilesional areas to assume function.

Seizures in adolescents.

The management of a patient with seizures involves proper classification, etiologic evaluation, and administration of appropriate therapy. With proper evaluation and management, control of seizures can be expected in the majority of patients. The physician must realize that an epileptic adolescent has intrinsic anxieties and faces social, educational, and vocational restrictions. Failure to deal with these psychosocial problems may result in a greater handicap to the patient than the seizures themselves.