Spinal intramedullary glioblastoma with intracranial seeding. Report of a case.

Approximately one year after partial removal of an intramedullary glioblastoma at T12, a patient was admitted to Wadsworth Veterans Administration Hospital with signs and symptoms of an intracranial tumor. We describe the unusual occurrence of intracranial seeding from spinal glioblastoma and review this rare condition and the possible mechanism involved.

Intracerebroventricular bethanechol for Alzheimer's disease. Variable dose-related responses.

Five male patients participated in a pilot open-label study of dose-related aspects of response to intracerebroventricular bethanechol in Alzheimer's disease. No patient had remission of symptoms, but three patients improved symptomatically and on tests of memory. Improvement was evident over a restricted range of doses for each subject, and symptoms were worse at doses below and above the optimal range. There was little overlap in the range of doses producing improvement among these three. Two patients had no consistent improvement in memory, and agitation, depression, paranoia, and seizures developed during treatment. Qualitative differences and variability in dosages producing responses complicate the identification of true drug response in the treatment of Alzheimer's disease.

Progression of clinical deterioration and pathological changes in patients with Alzheimer disease evaluated at biopsy and autopsy.

OBJECTIVES: To quantify the progression of senile plaques, neurofibrillary tangles, cerebral amyloid angiopathy, and microglial activation in the cortex and white matter of patients with Alzheimer disease evaluated at both biopsy and subsequent autopsy and correlate these changes with the progression of neurologic impairment. SETTING: Academic referral center for patient with Alzheimer disease. PATIENTS: Four patients meeting the clinical criteria for Alzheimer disease, enrolled in a pilot study for the evaluation of response to intracerebroventricular administration of bethanechol chloride. The patients were followed up until death occurred and autopsy was performed. RESULTS: All 4 patients had progressive deterioration from the time of biopsy to autopsy (9-11 years). Pathological investigations showed a striking increase in the density of senile plaques and neurofibrillary tangles in 2 of 4 patients from biopsy to autopsy, and a significant increase in microglial activation in 1 of 4 cases. Severity of cerebral amyloid angiopathy varied significantly among patients, 1 of whom displayed striking amyloid deposition with associated subcortical white matter atrophy. CONCLUSIONS: These unique data demonstrate that the progressive neurologic impairment in Alzheimer disease is accompanied by a significant increase in senile plaque and neurofibrillary tangle counts in the frontal cortex and, possibly in some patients, by increased microglial cell activation. Cerebral amyloid angiopathy was associated with significant white matter disease.

Primary position upbeat nystagmus. A clinicopathologic study.

Eye movements were studied with electro-oculography in a patient with primary position, large amplitude, upbeat nystagmus. The upbeat nystagmus increased in amplitude on upward gaze, decreased on downward gaze, and was not altered by loss of fixation. The patient could not produce smooth pursuit movements upward or to the left, but had normal saccadic and vestibular induced eye movements in all directions. At necropsy, a low grade glioma was found involving primarily the medulla and caudal pons. The inferior olives and prepositus hypoglossal nuclei were diffusely infiltrated with tumor. These results suggest (1) primary position upbeat nystagmus is due to a defect in the upward smooth pursuit system, (2) the lower brain stem at the level of the inferior olives and nucleus prepositus hypoglossi is important in the mediation of vertical pursuit, and (3) primary position upbeat nystagmus can result from damage to several nuclei and interconnecting pathways in the caudal brain stem and midline cerebellum involved in control of vertical smooth pursuit.

Amnesia with hippocampal lesions after cardiopulmonary arrest.

A patient developed an amnesic syndrome after cardiopulmonary arrest. Neuropathologic examination revealed pronounced anoxic injury to both hippocampi with little damage to other hemisphere structures. The clinical and pathologic findings suggest that lesions limited to the hippocampus can cause profound amnesia.

Dementia with Lewy bodies: reliability and validity of clinical and pathologic criteria.

Clinical criteria for dementia with Lewy bodies (DLB) have been proposed, but their formulation, reliability, and validity require further study. Pathologic criteria for DLB are also undergoing evolution. Two studies were conducted with the goal of identifying the components of these evolving criteria that may benefit from further refinement; one study evaluated the components of the clinical criteria and another study operationalized the pathologic criteria for DLB. Twenty-four patients with a premorbid diagnosis of probable or possible Alzheimer's disease (AD) (n = 18), Parkinson's disease (PD) (n = 5), or progressive supranuclear palsy (PSP) (n = 1) were studied. Inter-rater reliability and validity of the clinical criteria were determined by a retrospective chart review, done by five neurologists, and a blinded pathologic evaluation. The Consortium on dementia with Lewy bodies (CDLB) pathologic criteria were operationalized to compare past criteria and test the validity of the evolving clinical criteria on the dementia patients. Three or more cortical fields (at 250 x magnification) with many (four or more) Lewy bodies (LBs) on ubiquitin immunoreactive sections were required to meet the CDLB neocortical score of > 6. Fifteen of the AD patients had at least one LB in a cortical section, four had many LBs, while three had no LBs; all patients with movement disorder had at least one LB in a cortical section. The sensitivity/specificity ratio of the CDLB probable DLB clinical criteria based upon many LBs being present was 75%/79%. Reformulated clinical criteria that require the presence of extrapyramidal signs significantly predicted those patients with many LBs versus those with few or no LBs (chi 2 = 5.48, p = 0.02) and increased clinical specificity to 100%. This preliminary study identifies components of the evolving clinical and pathologic criteria for DLB that require further refinement.

Lymphomatoid granulomatosis and malignant lymphoma of the central nervous system in the acquired immunodeficiency syndrome.

While primary and secondary malignant lymphomas have been well-documented in the CNS of patients with the acquired immunodeficiency syndrome (AIDS), only one case of lymphomatoid granulomatosis (LG) involving the CNS has been reported. We present three AIDS patients with multiple grossly evident foci of necrosis in the cerebral hemispheres which, on histologic evaluation, were seen to contain angiocentric mixed chronic inflammatory infiltrates with atypical mononuclear cells, luminal thrombosis, and infarction, which is typical of LG. LG was also identified in sections of the lung in one case. Lymphoma was found in other regions of the brain in two cases, suggesting the evolution of LG into cerebral lymphoma. In addition, widespread perivascular multinucleate syncytial giant cells, associated with human immunodeficiency virus (HIV) infection of the CNS, were identified in all patients. The features of LG, its relationship to lymphoma, and the possible etiologic role of an immunodeficiency state or the HIV virus in the pathogenesis of LG are discussed.

Progressive multifocal leukoencephalopathy in AIDS: a clinicopathologic study and review of the literature.

We reviewed the clinical, radiographic, and pathologic features of 15 patients with the acquired immune deficiency syndrome (AIDS) and progressive multifocal leukoencephalopathy (PML). Brain tissue from 10 autopsy and 6 biopsy specimens was studied using: in situ hybridization (ISH) for JC virus (JCV), immunohistochemistry for human immunodeficiency virus (HIV) p24 antigen, and electron microscopy. Thirteen patients presented with focal neurologic deficits, while 2 presented with a rapid decline in mental status. PML was commonly the initial opportunistic infection of AIDS and produced hemiparesis, dementia, dysarthria, cerebellar abnormalities, and seizures. Magnetic resonance imaging was more sensitive than computed tomography in detecting lesions, and often showed multifocal areas of PML. CD4+ T-cell counts were uniformly low (mean 84/mm3), except in 1 patient who improved on 3'-azido-3'-deoxythymidine (AZT). PML involved the cerebral hemispheres, brain stem, cerebellum, and cervical spinal cord. The distribution of brain involvement was consistent with hematogenous dissemination of the virus. In 2 brain specimens, multiple HIV-type giant cells were present within the regions involved by PML. When co-infection by HIV and papovavirus was present, PML dominated the pathological picture. ISH for JCV showed virus in the nuclei of oligodendrocytes and astrocytes. Occasionally there was staining for JCV in the cytoplasm of glial cells and in the neuropil, the latter possibly a correlate of papovavirus spread between myelin sheaths, as seen by electron microscopy. ISH demonstrated more extensive foci of PML than did routine light microscopy.

Multiple radiation-induced intracranial lesions after treatment for pituitary adenoma. Case report.

This 53-year-old man presented with a syncopal episode 31 years after undergoing craniotomy and external-beam radiation for a pituitary macroadenoma. A gadolinium-enhanced magnetic resonance (MR) image of the brain demonstrated a 2.5-cm enhancing mass in the right caudate region that had not been seen on previous studies. A stereotactically guided biopsy procedure was performed to obtain specimens from the mass, which were consistent with ependymoma. The MR image also revealed two additional lesions that appeared to be within the radiation fields: a right temporal meningioma and a left frontal cavernous malformation. A review of the literature found three previous reports in which ependymomas presented after radiation therapy.

Central nervous system amyloid presenting as a mass lesion. Report of two cases.

Amyloidomas of the central nervous system are rare. Two cases involving middle-aged patients with neurological symptoms are presented. Massive focal accumulations of amyloid in the cerebral hemispheres were confirmed pathologically.

Rebound phenomenon complicating cerebral dehydration with glycerol. Case report.

A patient with glioblastoma multiforme of the brain was treated with both intravenous and oral glycerol as well as intravenous mannitol in an attempt to reduce increased intracranial pressure. After an initial lowering of the cerebrospinal fluid (CSF) pressure to near normal values during continuous glycerol administration, a secondary rise in CSF pressure above the initial level occurred despite a persistent elevation of plasma osmolality (315 mOsm/kg) and glycerol level (30 mmole/l). Similarly, 4 hours after the administration of a single oral dose of glycerol, CSF pressure increased to levels higher (700 mm H2O) than the original baseline (400 mm H2O).

Altered behavior associated with damage to the ventromedial hypothalamus: a distinctive syndrome.

An adult manifested a tetrad of neurobehavioral findings consisting of episodic rage, emotional lability, hyperphagia with obesity, and memory impairment with intellectual decline following surgical removal of a craniopharyngioma. Post-mortem investigation of the topography of the lesion as well as review of previously reported cases suggest that this tetrad represents a specific neurobehavioral syndrome referable to damage to the ventromedial hypothalamus.

Subdural neomembranes and sudden infant death syndrome.

Cranial dura maters of 36 consecutive infants with sudden infant death syndrome (SIDS) and 16 control infants coming to the Department of Coroner were examined microscopically to determine if subdural neomembranes are associated with cases submitted as SIDS. Thirty-one percent (31%) of the infants with SIDS and 13% of control infants had organizing subdural neomembranes (p > 0.05). Overall prevalence of organizing subdural neomembranes was 25% in the group examined. In all but two cases, birth trauma could be excluded as a cause of head trauma by aging neomembranes histologically. No association was found between type of delivery (vaginal or Cesarean) and presence of a subdural neomembrane. Subdural neomembranes are common in infants autopsied in a forensic setting, but they may be missed without a microscopic examination. Subdural neomembranes have no demonstrated association with SIDS.

Denervation microangiopathy in senile dementia, Alzheimer type.

Structural analysis of the capillary plexus in the brains of 5 patients with clinical and neuropathological diagnosis of Senile Dementia, Alzheimer Type, revealed a group of striking physical alterations compared with tissue specimens from 5 age-matched controls. Capillary walls were thickened with irregular lumpy, nodulated contours which appeared due, in part, to infiltration of the vascular wall with rounded cell-like bodies. In some cases, these resembled the perikarya of pericytes or monocytes, or their protoplasmic extensions, which were often filled with lipids. In each case, there was no trace of the perivascular neural plexus which regularly invests the microvasculature of the brain parenchyma. The loss of this neural plexus, believed to originate largely from locus ceruleus and the basal forebrain, may be related to the changes in capillary wall structure, and these, in turn, may lead to profound alterations in blood-brain barrier function. We suggest that this subcortically induced denervation microangiopathy may serve as a pathogenic factor in the development of SDAT.

Prognosis of pituitary adenomas with arteriographic abnormal vascularization.

A case report and five additional cases from the literature of angiographically demonstrated abnormal vascularization of chromophobe adenomas are presented. The appearance is that of a fine network of vessels appearing in the arterial phase and a homogeneous blush beginning in the capillary phase and lasting throughout the venous phase. The network is derived from dilated branches of the extradural internal carotid artery and is seen in the arterial phase. The stain, appearing in the venous phase, is due to filling of tiny sinusoidal channels and thin-walled vessels throughout the stroma. All the patients had large, actively growing tumours which compressed and infiltrated surrounding structures. Complete tumour removal was not possible in the patients operated upon. The combined morbidity-mortality rate was 83% and was due to the large tumour size, adherence to vital centres, extreme vascularity during surgical removal, and propensity to bleed spontaneously. The appearance of abnormal vascularity in a pituitary adenoma suggests a poor prognosis.

Neuroimaging in temporal lobe epilepsy: test sensitivity and relationships to pathology and postoperative outcome.

We studied patients with documented temporal lobe seizures to evaluate the predictive value of computed tomography (CT), magnetic resonance imaging (MRI), and F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) for surgical therapy and the relationships between these tests and the pathologic diagnoses. CT detected abnormalities in 32.5%, with an accuracy of 19% when accuracy was defined as congruence with electrophysiologic studies. MRI detected abnormalities in 81%, with an accuracy of 67%. FDG-PET detected abnormalities in 85%, with an accuracy of 82%. Pathologic change was detected in 79% of the excised temporal neocortex, 65% of amygdalae, and 93% of hippocampi. After follow-up periods of 20-71 months (mean 41 months), 67% of patients were free of seizures and 94% had at least a 90% reduction in seizure frequency. There was no relationship between the type of abnormality on MRI or the type of pathology and postoperative outcome. Better outcomes were associated with focal or regional ictal onsets as recorded by surface EEG. Worse outcomes were associated with hypometabolism that extended outside the temporal lobe. Pathologic change in the temporal neocortex was associated with extension of hypometabolism outside the temporal lobe.