Phase II trial of primary chemotherapy followed by reduced-dose radiation for CNS germ cell tumors.

PURPOSE: A prospective phase II study was initiated to assess the response rate, survival, and late effects of treatment in patients with newly diagnosed CNS germ cell tumors (GCT), using etoposide plus cisplatin followed by radiation therapy prescribed by extent of disease, histology, and response to chemotherapy. PATIENTS AND METHODS: Seventeen patients aged 8 to 24 years with histologically proven CNS GCT received etoposide (100 mg/m2/d) plus cisplatin (20 mg/m2/d) daily for 5 days every 3 weeks for four cycles, followed by radiation therapy. Nine patients had germinomas; eight had mixed GCT. Four patients (three with germinomas and one with mixed GCT) presented with leptomeningeal dissemination. RESULTS: Radiographically, 14 of 17 patients were assessable for response; 11 patients experienced complete regression, and three had major partial regression before radiation. Six of seven assessable patients with elevated CSF levels of alpha-fetoprotein or betahuman chorionic gonadotropin had normalization with chemotherapy alone; all normalized with combined chemotherapy and radiation therapy. All 17 patients are alive without evidence of disease (median follow-up, 51 months). One patient developed a relapse in the spinal leptomeninges and was rendered free of disease with spinal radiation more than 5 years ago. One patient developed carotid stenosis requiring surgery. Thus far, only minimal long-term deterioration in neurocognitive function has been detected as a consequence of protocol treatment. CONCLUSION: Conventional-dose intravenous chemotherapy with etoposide and cisplatin can effect tumor regression in a high proportion of patients with CNS GCT, including those with leptomeningeal metastases. Acute and long-term toxicities are acceptable. Progression-free survival and overall survival are excellent.

Pituitary adenomas in childhood and adolescence.

A clinicopathological study of 56 pediatric patients with non-ACTH-secreting pituitary adenomas removed by a transsphenoidal neurosurgical approach was undertaken to better define the clinical presentation, to assess demographic factors, to determine the immunohistochemical staining characteristics of the tumors, and to evaluate the outcome of transsphenoidal surgical treatment and other adjuvant therapies. A separate analysis of prolactinoma patients was performed. All tumors were confirmed histologically and immunophenotyped for pituitary hormones. Forty-one patients had tumors that stained for PRL alone, eight patients had tumors that stained for PRL and GH, six patients had plurihormonal adenomas, and one patient had a tumor that stained for glycoprotein hormones. No tumors contained GH alone. Macroadenomas exceeded microadenomas (1.4:1). There were no male patients with microadenomas of any type. Females outnumbered males (3.3:1). Patients presented most frequently with headache, menstrual dysfunction (in females), galactorrhea, and hypopituitarism. All but one of the patients with hypopituitarism at presentation had macroadenomas. Tumor staining characteristics did not always correlate well with clinical status, especially with regard to GH-containing tumors. Pediatric pituitary tumors did not appear to be more invasive or more aggressive than adult pituitary tumors, contrary to some previous reports. The patients with microadenomas had a 70% operative cure rate and a 65% long term cure rate; the recurrence rate for microadenoma patients was 25%. Macroadenoma patients had a 33% operative cure rate, a 55% long term cure rate, and a recurrence rate of 33%. Thus, microadenoma and macroadenoma patients had similar long term cure rates, but macroadenoma patients required more aggressive adjuvant therapy (second surgery, radiation, or bromocriptine) and had higher rates of hypopituitarism (52% of macroadenoma patients vs. 0% of microadenoma patients required long term hormone replacement).

Cerebral palsy--trends in incidence and changes in concurrent neonatal mortality: Rochester, MN, 1950-1976.

We studied all identified cases of cerebral palsy (CP) born to residents of Rochester, MN, during a 27-year period. Incidence rates per 1,000 neonatal survivors were computed for three 9-year intervals. For children with persisting findings, the incidence rate of all syndromes declined from 2.3 to 1.6. For spastic syndromes, this trend was more marked (2.1 to 0.9). For newborns with birthweight over 2,500 g, both CP incidence and neonatal mortality rates (NMR) declined in parallel. For the low birthweight neonate, coincident with a precipitous drop in NMR, the CP incidence rate remained essentially unchanged. In the face of increasing neonatal survival, the overall incidence rate of CP declined. The decrease in the absolute risk of CP was limited to the greater than 2,500-g neonatal survivor.

Cerebral palsy: survival rates, associated handicaps, and distribution by clinical subtype (Rochester, MN, 1950-1976).

We identified 64 cases of cerebral palsy (CP) born to Rochester residents in 1950-76. The majority (73%) had one of the spastic syndromes. Ataxic and dyskinetic syndromes constituted 16% and 6%, respectively. Survival follow-up was available through 1980 birthdates. Using life-table methods, we calculated survival rates for the first 10 years of life. For severely or profoundly retarded children, survival was 68% at 5 years and 54% at 10 years. All others survived through their 1980 birthday. Follow-up of CP resolution was available through the seventh birthday. Cases born in 1968-76 had the highest resolution rate (30%). For mild CP, the 1968-76 resolution rate was 86%.

Seizures after head trauma: a population study.

A cohort of 2747 patients with head injuries was followed for 28,176 person-years to determine the magnitude and duration of the risk of posttraumatic seizures. Injuries were classified as severe (brain contusion, intracerebral or intracranial hematoma, or 24 hours of eight unconsciousness of amnesia), moderate (skull fracture or 30 minutes to 24 hours of unconsciousness or amnesia), and mild (briefer unconsciousness or amnesia). The risk of posttraumatic seizures after severe injury was 7.1% within 1 year and 11.5% in 5 years, after moderate injury the risk was 0.7 and 1.6%, and after mild injury the risk was 0.1 and 0.6%. The incidence of seizures after mild head injuries was not significantly greater than in the general population.

Etiology and outcome in 42 children with acute nonbacterial meningoencephalitis.

In a prospective study of 42 cases of childhood meningoencephalitis occurring in 1974 and 1975, a diagnosis of an infectious agent was made in 30 (71%). California virus infections were most common; they were serious illnesses but had few sequelae. Benign illnesses with enteroviruses were also common. Miscellaneous and unknown agents accounted for the most seriously ill patients and for both deaths. Persistent neurologic deficits were unusual. Headaches, malaise, and changes in behavior were common but transient.

Chronic inflammatory polyradiculoneuropathy.

The diagnostic criteria, natural history, nerve conduction characteristics, pathology, laboratory features, and efficacy of corticosteroid treatment have been evaluated personally in 53 patients with chronic inflammatory polyradiculoneuropathy (CIP) who were followed up for an average of about 7.5 years. These were patients whose monophasic neurologic deficit had not crested by 6 months, patients with recurrences, and patients with a steady or stepwise progression. The typical features of CIP include absence of an associated disease, frequent history of preceding infection or receipt of foreign protein, and tendency to involve cranial, truncal, and proximal as well as distal limb structures and to have diffusely slow conduction velocity of peripheral nerves. The most marked slowing is often very proximal. The pathologic features include serous edema, mononuclear cell infiltrates (especially in perivascular areas, but without evidence of vasculitis), macrophage-induced segmental demyelination, and hypertrophic neuritis. If our patients are representative, complete recovery occurs only infrequently; about 60% of patients are able to be ambulatory and work, 25% become confined to a wheelchair or become bedridden, and approximately 10% die from their disease. Although the bulk of the pathologic changes affect spinal roots and proximal nerves, the brain and spinal cord may be involved also. Degeneration into linear rows of myelin ovoids is the predominant type of myelinated fiber degeneration of the sural nerve at the ankle.

Juvenile temporal arteritis revisited.

We describe a case of arteritis involving the superficial temporal artery in an 8-year-old boy. After a 2-week prodrome of headache in the right temporal region, a painful pulsatile 6-mm nodule developed. No history of trauma or systemic disease was noted. The differential diagnosis included vasculitis or thrombosis of a vascular malformation of the temporal artery. The lesion was surgically excised for both diagnostic and cosmetic reasons. Histologic features of the nodule were diagnostic of juvenile temporal arteritis and characterized by non-giant cell granulomatous inflammation of the temporal artery, occlusive fibrous intimal proliferation, and microaneurysmal disruption of the media. At 12-month follow-up, the patient was well; no recurrent lesions or systemic disease was noted. Although rare, this disease should be recognized as arteritis that affects the external carotid circulation and should not be confused with classic giant cell temporal arteritis. If physicians are aware of this benign inflammatory disease of the temporal artery in children and young adults, unnecessary treatment will not be administered.

Primary cardiac myxosarcoma in a child.

This is a detailed clinical and autopsy documentation of a rare entity--primary cardiac myxosarcoma in a 29-month-old girl. The patient had sudden onset of right hemiplegia and angiographic evidence of multiple occlusions of the left middle cerebral artery. Subsequent M-mode and sector echocardiography showed a mobile, pedunculated left atrial tumor, which was excised. No other tumor mass was noted at the time of surgical exploration, and postoperatively, the patient received a course of chemotherapy (vincristine, dactinomycin, and cyclophosphamide). After a temporary improvement in her condition, the patient died following several days of rapid deterioration; this was 3 months after the onset of symptoms. Autopsy showed that death was due to brainstem herniation secondary to massive infiltration of the brain by tumor, and there were also widespread systemic metastases.

Central pontine myelinolysis as a complication of partial ornithine carbamoyl transferase deficiency.

Central pontine myelinolysis (CPM) is a demyelinating condition of the central pons with or without associated foci of demyelination in extrapontine areas. We present a case of partial ornithine carbamoyl transferase deficiency in a 5-year-old girl which was complicated by CPM. The patient was a previously undiagnosed girl who presented with mild hyperammonemic encephalopathy with a maximum plasma ammonia level of 376 microM on admission. Laboratory testing established the diagnosis of OCT deficiency, and therapy with hydration and protein restriction was successful in returning the plasma ammonia levels to normal. Five days after correction of her hyperammonemia, the patient developed intractable seizures and coma. Serial MRI scans of the brain revealed the evolution of the characteristic findings of CPM. Plasma ammonia and electrolyte concentrations were well controlled throughout this time. This represents the first description of CPM in a patient with a urea cycle defect.

Spontaneous sleep and induced arousal. A depth-electroencephalographic study.

Although arousal effects from electric stimulation have been found in animals, reports of similar responses in humans have been uncommon. During depth electroencephalography in a 16-year-old boy for evaluation of intractable temporal lobe seizures, electric stimulation of a pair of contact leads located within the dorsal and medial portions of the thalamus but not within specific sensory nuclei produced unequivocal behavioral and electrographic arousals from spontaneous sleep. Lowvoltage stimuli were effective during non-REM and REM sleep. These findings verify the presence of a thalamic arousal system in the human.

Medulloblastoma: I. Clinical, diagnostic, and therapeutic overview.

Medulloblastoma, the most common embryonal tumor of the central nervous system, affects both children and adults. It poses a significant therapeutic challenge in that age-dependent differences exist, not only in their pathobiology, but in the efficacy of chemotherapy and radiotherapy. This is particularly the case in very young children, whose still developing nervous system exhibits a low tolerance to radiotherapy. We review the epidemiology, clinical presentation, radiologic features, and current therapeutic concepts relative to this unique neoplasm. Efforts are made to highlight clinical controversies.

Preliminary communication--treatment of primary brain tumors recurrent after irradiation with aziridinylbenzoquinone (AZQ;NSC-182986).

Twenty-nine patients with primary brain tumors recurrent or progressive after cerebral irradiation were treated with AZQ. Twenty of the 29 patients had also failed prior chemotherapy. CT scan-documented tumor regressions were noted in 17.2% (5/29) and ranged from 15.0% (3/20) in patients with prior chemotherapy to 22.2 (2/9) in patients without prior chemotherapy. Myelosuppression was the only significant toxicity noted. AZQ is worthy of further studies in patients with primary brain tumors.

Skeletal, cardiac, and smooth muscle failure in Duchenne muscular dystrophy.

The goals of this study were to describe the clinical course of skeletal, cardiac, and gastrointestinal muscle manifestations and trends in age at diagnosis and survival of Duchenne muscular dystrophy (DMD) patients. A retrospective cohort of 33 male patients with DMD, born between 1953 and 1983 and followed at the Mayo Clinic during their second decade of life, was studied. The mean age at DMD diagnosis was 4.6 years. Skeletal muscle weakness present in all patients at diagnosis progressed to wheelchair dependency in 32 patients (97%) by the age of 13 years (median age 10 years). Cardiac muscle failure developed in 5 patients (15%) (median age 21.5 years). Smooth muscle manifestations related to the digestive and urinary tracts occurred in 7 (21%) and 2 (6%) patients (median age 15 years), respectively. The gastrointestinal dilatations were primary in 2 patients or secondary to surgery or acute respiratory illness in 5 patients. By the end of the study period, 17 deaths had occurred (median age 17 years). Over time, there was a decrease in the time to DMD diagnosis (P = .05) but no significant change in survival (P = .44). Cardiac and smooth muscle manifestations occur late in the course of DMD. Clinical gastrointestinal symptoms related to smooth muscle function most often were secondary to surgery or a respiratory illness. In recent years, the diagnosis of DMD has been made at a younger age, but survival has not changed.

Clinical outcome in children with acute cerebellar encephalopathy and neuroblastoma.

Acute cerebellar encephalopathy (ACE)--ataxia often associated with opsoclonus, polymyoclonus, and irritability--may be associated with neuroblastoma and should be suspected in a child who presents with ACE. The survival in ten children with ACE associated with neuroblastoma was 100%. Most of the tumors were ganglioneuroblastomas. The abdomen was the most common location for the tumor in this study although it also can be found in the mediastinum. All patients with this syndrome had a localized tumor. With ACTH therapy, ACE may resolve early postoperatively, but it tends to recur in most patients, continuing for as long as 3 years after the initial operation. Treatment with ACTH or prednisone modifies and rapidly clears the symptoms during the acute episode of recurrent ACE as well as helps to resolve subsequent neurologic sequelae. Significant neurologic sequelae persisted in seven of ten patients and included deficits in cognition or intellect, hyperactivity, impulsivity, emotional lability, and mild motor deficits. Seizures were seen in one patient.

Acne fulminans and myositis.

Acne fulminans is characterized by highly inflammatory ulcerative lesions and systemic manifestations. We report a case of acne fulminans and myositis. In addition to having typical skin changes, the patient was unable to walk and electromyographic studies showed significant changes.