Treatment of human malignant meningiomas by G207, a replication-competent multimutated herpes simplex virus 1.

We have demonstrated that replication-competent attenuated mutants of herpes simplex virus type 1 (HSV-1) have therapeutic potential for malignant gliomas. Moreover, a recently described multiple mutant HSV (termed G207) has properties which may allow human clinical trials. G207 is able to replicate within and kill cells from three human malignant meningiomas in cell culture. In nude mice harboring s.c. human malignant meningioma (F5), G207 can inhibit growth in a dose-dependent fashion. In nude mice harboring intracranial subdural human malignant meningioma (F5), one injection of G207 caused significantly decreased tumor growth and one apparent cure with neither neurological dysfunction nor pathological changes in the surrounding brain. These results suggest that G207 should be considered for therapeutic trials in the treatment of malignant meningioma refractory to currently available therapies.

Cortical degeneration with swollen chromatolytic neurons: its relationship to Pick's disease.

We report two cases of dementia in which cortical degeneration with widespread swollen chromatolytic neurons (SCN) was the dominant pathologic feature. Each patient had received the diagnosis of Alzheimer's disease on the basis of clinical findings. There was no deficit of cortical choline acetyltransferase activity, assayed in one case, or lesions of the nucleus basalis of Meynert. The brains had moderate to marked frontal atrophy. Comparison of SCN with several other cerebral degenerative disorders indicates a similarity with certain features of the transmissible spongiform encephalopathies and with corticodentatonigral degeneration. The pathologic features of our cases are those of a number of other cases reported as "Pick's disease," and may represent an earlier stage in the pathogenetic process than the severe, sharply circumscribed atrophy with "nonspecific" cell loss and gliosis as the only microscopic residuals. Our findings re-emphasize the need to search for pathogenetically distinct subgroups which have been wholly or partially subsumed into the concept of Pick's disease.

Lymphocytic adenohypophysitis causing pituitary mass.

Lymphocytic infiltration of the anterior pituitary is a rare complication of pregnancy, which has been reported in 18 cases. Symptoms begin in the last trimester or soon after delivery. Radiologically, an expanding mass in the sella may result in suprasellar extension. We studied a case in which there was CT evidence of a pituitary mass 2 weeks postpartum, and biopsy confirmed the diagnosis.

Pathologic findings in a steroid-responsive optic nerve infarct in giant-cell arteritis.

OBJECTIVE: To investigate the pathophysiologic mechanism of optic nerve infarction in giant-cell arteritis (GCA). BACKGROUND: Previous pathologic reports of optic nerve infarction in GCA involved patients who were blind at the time of death. The optic nerve infarcts were primarily retrolaminar in localization. Simultaneous short ciliary and ophthalmic artery vasculitis was found in all patients. METHODS: Clinical neurologic and ophthalmologic examination, temporal artery biopsy, and neuroimaging tests were performed in a patient with an anterior ischemic optic neuropathy secondary to GCA. Pathologic examination of the viscera, eye, and brain were performed at autopsy 1 month later. RESULTS: A prelaminar/retrolaminar infarct was found in this patient. Subsiding vasculitis was limited to the short ciliary arteries, sparing the central retinal, pial, and ophthalmic arteries. CONCLUSIONS: The authors believe that the visual improvement observed in this patient was the result of preserved, anterior optic nerve collateral circulation, as well as the neuroprotective and anti-inflammatory effect of the corticosteroids.

Cytomegalovirus encephalitis associated with episodic neurologic deficits and OKT-8+ pleocytosis.

After 3 days of symptoms suggesting a viral illness, a 35-year-old man experienced three episodes of aphasia, right-sided sensory symptoms, and bifrontal headache. Each lasted several hours. CSF examination revealed a moderate lymphocytosis consisting of 80% OKT-8+ cells. Serum anti-cytomegalovirus (anti-CMV) antibody titer was elevated at 1:1,024 and subsequently fell to 1:64. Episodic symptoms recurred 5 months later, at which time the anti-CMV titer peaked at 1:8,192. A trial of inhaled oxygen aborted two episodes after several minutes each.

Type-specific identification of herpes simplex and varicella-zoster virus antigen in autopsy tissues.

To identify antigens of herpes simplex virus (HSV) types 1 and 2 and varicella-zoster virus (VZV) in human tissue, polyclonal antisera and an immunoperoxidase method were used to examine formalin-fixed, paraffin-embedded tissues from autopsy cases and experimentally infected animals. These antisera readily distinguished between HSV and VZV antigen, with no evident cross-reactivity. Antiser ato HSV-1 and HSV-2 were more strongly reactive with antigen of the homologous virus than with that of heterologous virus. This difference in immunoreactivity was used to discriminate between HSV-1 and HSV-2 antigens in experimentally infected animal tissues containing HSV antigens of known type and, by extrapolation, to distinguish between these antigens in human autopsy tissues. Thus, with appropriate antisera and tissue controls, HSV-1, HSV-2, and VZV can be identified in paraffin sections.

Cutaneous malignant melanoma in survivors of heritable retinoblastoma.

Six survivors of bilateral retinoblastoma developed cutaneous malignant melanoma 20 to 51 years (average, 31 years) after initial therapy for the ocular tumor. Five patients received radiation therapy to the orbital area. In two patients the cutaneous malignant melanoma developed in the field of irradiation. Two patients developed multiple cutaneous melanomas and are thought to have the dysplastic nevus syndrome. At this writing two patients are alive and well after wide resection of their skin tumors. A review of the literature suggests that cutaneous malignant melanoma accounts for about 7% of second malignant neoplasms in survivors of heritable retinoblastoma.

Malassezia furfur--disseminated infection in premature infants.

Three infants, born prematurely, died after clinical illnesses of 67, 65, and 60 days from infection by Malassezia furfur. Each infant had been nourished with lipid emulsions delivered through deep-line catheters. The infections, all discovered at autopsy, were characterized by massive involvement of lungs. Two of the three had endocardial vegetations containing M. furfur; all three had lesions in liver, kidney, and spleen, and two had lesions in adrenal, pancreas, and colon. In addition, one of the infants had acute meningoencephalitis caused by M. furfur. In some of the distant organs, yeast cells of M. furfur were growing in the lumina of small vessels, filling the lumina, but causing no vasculitis or infarction. In addition to these benign collections of yeasts within vessels, there were acute inflammatory lesions as well. These were consolidation, vasculitis, granulomatous inflammation, septic thrombosis, and septic infarction of lung and foci of necrosis and inflammation in kidney and liver. Two previously reported autopsies described neonates with lesions in lung and heart. The authors' three cases for which autopsies were performed had lesions in lung and heart too but, in addition, had dissemination with acute lesions in kidney and liver. Finally, one patient had a severe meningoencephalitis caused by M. furfur.

Peliosis hepatis after long-term androgen therapy.

Peliosis hepatis is a recognized, but rare, complication of androgen replacement therapy. We herein report such a complication with necropsy study of the liver so involved.

Neurogenic fibrosarcoma following radiation therapy for seminoma.

We report a case of radiation-induced neurogenic fibrosarcoma that developed in a patient who received radiation therapy for seminoma. The sarcoma developed within the irradiated field after a latency period of nineteen years. Although the occurrence of a secondary neoplasm is unusual, this possibility should be included in the differential diagnosis of patients who present with tumor growth after a long interval following radiation therapy.

Pathologic fracture of odontoid process secondary to amyloid deposition.

Immunocyte dyscrasias have increasingly been reported in patients with gammopathy-associated systemic amyloidosis. In "primary" amyloidosis, deposits occur in heart, smooth and skeletal muscle, bones and joints, skin, lungs and peripheral nerves. The formation of amyloid fibrils appears related to the lambda light chains in these monoclonal gammopathies. A 72-year-old white man is reported who developed massive deposits of amyloid in joints and bones, as well as other tissues. Twenty percent of his bone marrow population was comprised of plasma cells in various maturational stages, without forming solitary masses diagnostic of myeloma. Lambda light chains were the sole contributors to a selective increase in IgD, with a concomitant reduction of IgA, IgG, and IgM. The patient sustained a pathologic fracture through a deposit of amyloid in the odontoid. While he suffered severe posterior nuchal and occipital pain, no clinical features of compression myelopathy were evident. Postmortem examination revealed a minor degree of posterior column degeneration and an axonal reaction of anterior horn cells of the C-1 spinal cord segment. This case represents the second to be reported with amyloidosis of the vertebral column, pathologic fracture, and a spinal cord lesion.

Dissecting aneurysm of intracranial vertebral artery: case report and review of literature.

A spontaneous dissecting aneurysm of the intracranial portion of the dominant right vertebral artery presented as massive subarachnoid hemorrhage, excruciating headache, and respiratory arrest in a 57-year-old white man with a history of systemic hypertension. He died on the 3rd day. Postmortem examination revealed a dissecting hemorrhage extending for 2.1 cm along the artery; rupture of the intima, media, and adventitia could be demonstrated. The intramural accumulation of blood in the proximal segments appeared to be related to retrograde dissection within a media weakened by cystic degeneration. Accumulation of pools of mucoid ground substance was also demonstrated in other intracranial and extracranial arteries. Hemodynamic stresses due to arterial hypertension and physical exertion may have played a contributory role in the etiopathogenesis of this uncommon form of cerebrovascular accident. A comprehensive literature review permits a comparison of supratentorial and infratentorial dissecting aneurysms; vertebral and basilar artery dissections are presented in tabular form.

An unusual case of central nervous system vasculitis.

A patient with CNS vasculitis limited to small vessels is described. Initial spinal cord involvement with paraparesis was followed by multifocal cerebral and cerebellar involvement, depicted by magnetic resonance imaging (MRI). She also had recurrent cerebral bleeding. A diagnosis of vasculitis was made by cerebral biopsy. Immunosuppressive therapy resulted in clinical improvement and resolution of the MRI abnormalities.

Ventricular septa in the neonatal age group: diagnosis and considerations of etiology.

Twenty-four patients with ventricular septa are discussed. Seventeen patients had septa acquired during the neonatal period and seven exhibited septations at birth (cogenital septa). Among the acquired septa, there were true intraventricular septa and septa that originated outside the ventricles but later became part of the ventricular system (pseudosepta). Pseudosepta originate in necrotic, cavitating periventricular white matter that, in temporal sequence, becomes ventricularized. Serial use of cranial sonography provided important information about the pathologic mechanisms that govern the development of septa. Intraventricular hemorrhage and infection are the major causes of true intraventricular septa, while periventricular leukomalacia serves as primary cause of pseudosepta. Sonography is the diagnostic method of choice. Septa are associated with a high incidence (62%) of shunt failure.

A clinical and neuropathologic study of silk suture as an embolic agent for brain arteriovenous malformations.

PURPOSE: To evaluate the safety and efficacy of silk suture as an agent for preoperative embolization of cerebral arteriovenous malformations. METHODS: Clinical and histopathologic results were analyzed in six patients who underwent embolization of cerebral arteriovenous malformations using silk suture in combination with other agents. RESULTS: Three of the patients treated with silk hemorrhaged after embolization, and two of these patients died. Neuropathologic analysis of four patients showed acute perivascular inflammation, sometimes quite severe. CONCLUSIONS: The inflammatory response to silk may explain its effectiveness in producing vascular occlusion. However, a fulminate vasculitis theoretically can predispose to delayed hemorrhage. Other problems with silk include the pressure required to inject the agent and the inability to determine the final site of deposition of the silk. Although other embolic agents may share some of these potential difficulties, we feel that the disadvantages outweigh the advantages of silk as an embolic agent.

Neuropathology, pathogenesis, and neuropsychiatric sequelae of Reye syndrome.

A clinico-pathologic correlation can be established for those survivors of Reye syndrome in the higher clinical stages who have sustained irreversible and often major neuropsychiatric deficits. The neuropathologic substrate for the clinical manifestations of mental retardation, recurrent seizures, movement disorders, sensori-motor deficits, psychobiologic maladjustment, and mediocre performance in school and on formal psychometric tests consists of multifocal infarction and astrocytosis in cerebral cortex, diencephalon, basal ganglia, and brainstem. While the mortality rate of Reye syndrome in acute stages is still significantly high (25% in our 20 cases, 52% in the tabulated cases in the higher clinical grades), the occurrence of permanent psychomotor deficits is an equally tragic socioeconomic and medical problem. Of our 15 survivors, 3 have suffered major and 1 has sustained minor brain damage. From a review of the literature, over one-third of survivors are consigned to cerebral malfunction, hence their potential for full enjoyment of life and their intellectual, emotional, and economic contributions to their families and society are sadly curtailed.

New phenotypic variant of adrenoleukodystrophy. Pathologic, ultrastructural, and biochemical study in two brothers.

Adrenoleukodystrophy is not usually considered in the differential diagnosis of the infantile onset of failure to thrive with motor and intellectual retardation. Rather, symptoms have started in childhood and have progressed over some years; not all patients have had overt adrenocortical insufficiency. The two brothers reported here developed symptoms in the neonatal period. In each the nature of the primary cerebral disorder was not recognized, because other etiologic factors clouded the diagnostic studies. In the younger brother, Case 1, a high titer (1:256) for cytomegalovirus (CMV) led to the suspicion that CMV infection accounted for the neurologic and ophthalmologic findings. Progressive neurologic deterioration at the age of 6 years prompted brain biopsy to confirm the diagnosis of progressive CMV encephalitis. In the older brother, Case 2, hemogenic hydrocephalus due to traumatic birth injury was held responsible for the psychomotor retardation and cerebral palsy. At necropsy, the adrenal glands in both cases were severly atrophic. In Case 1, a markedly inflammatory leukodystrophic process affected chiefly the frontal centra semiovalia and internal capsules, with relative sparing of parieto-occipital white matter and subcortical U-fibers. Heavy lymphocyte and monocyte cuffs surrounded many blood vessels in the white matter, and oil-red-O and PAS-positive macrophages were scattered in the zones of myelin disintegration and loss. Focally, the leukodystrophic process was so intense that cavitation necrosis was present, especially in the internal capsules. Further, PAS-positive, striated macrophages were aggregated in large clusters in liver, spleen, and lymph nodes. At the ultrastructural level, linear and gently arced, parallel, coapted or widely separated leaflets measuring 3-4 nm in width were identified in macrophages of the brain biopsy and in autopsy liver and lymph node. Biochemical analysis of fresh, frozen autopsy brain demonstrated cholesterol esters with long-chain fatty acids by thin-layer and gas-liquid chromatography. In Case 2, the leukodystrophic process could be readily identified in the brainstem and cerebellum but was masked in the cerebral hemispheres by the extensive hydrocephalus. The adrenal glands were atrophic and at light microscopy revealed adenomatoid nodules, many ballooned coritcal cells and very rare cells with striated cytoplasm. Masses of PAS-positive macrophages were encountered in liver and lymph nodes. In both cases, only old Wallerian degeneration of the corticospinal tracts was found in the spinal cord.

Large arachnoid cysts at the cranial base.

Two infants who presented with macrocephaly had very large noncommunicating cysts at the cranial base that were displacing the brain. Only one of the patients was hydrocephalic; he eventually underwent ventriculoperitoneal shunting after craniotomy and attempted internal drainage of the cyst. The other infant had a cystoperitoneal shunt. Both have done well after 4 and 6 years of follow-up, respectively. These large arachnoid cysts are bilateral lesions with the potential for severe surgical complications and a questionable possibility of cure. The authors recommend systematic radiological investigation to decide the appropriate therapy, including an analysis of the patency of the subarachnoid pathways with radionuclide cisternography and cystography. Simple cystoperitoneal shunting may be the appropriate therapy for most of these large lesions. (Neurosurgery, 6: 76--81, 1980).

Multiple oncotic intracranial aneurysms and cardiac metastasis from choriocarcinoma: case report and review of the literature.

Ten cases of oncotic intracranial aneurysms from choriocarcinoma have been reported previously. We report an eleventh case with four aneurysms secondary to metastatic choriocarcinoma. These aneurysms seemed to arise from cephalic embolization of neoplastic tissue from an implant of choriocarcinoma in the left ventricle of the heart.

Central spinal cord injury: magnetic resonance imaging confirmation and operative considerations.

A case of central cervical spinal cord injury, confirmed by magnetic resonance imaging (MRI) and treated by myelotomy, is presented. After recovering well from his central cord syndrome and walking with assistance, the patient developed a rapidly progressive myelopathy beginning 2 months after injury. His main injury localized clinically to the C8, T1 level; but central cord abnormalities were identified 3 months after injury at the C6 level by MRI: a high signal intensity on the proton density sequence and a low-signal intensity on the T1-weighted sequence. At operation 41/2 months after his injury and 1 month after complete paraplegia, a myelotomy at C6 failed to reveal any cavity (syrinx) but instead disclosed only intense gliosis inside a slightly atrophic spinal cord. Rapid clinical improvement ensued. Secondary syringomyelia may be an endstage condition after spinal cord insults that trigger a progressive, pathophysiological reaction leading to central cord necrosis. In selected cases, myelotomy may interrupt this MRI-identified, nosogenic process before cavitation has occurred.