Henry S. Schutta

Acute cerebellar dysfunction with high-dose ARA-C therapy

The authors report a patient with clinical and morphologic evidence of acute cerebellar toxicity after receiving high‐dose cytosine arabinoside (ARA‐C) (3000 mg/m2/12 hours) for refractory AML. Damage of Purkinje cells and dentate nucleus was demonstrated. Reversible cerebellar toxicity has previously been noted in patients on an identical regimen. Signs of cerebellar dysfunction mandate immediate cessation of highdose ARA‐C therapy.

Cerebral Venous Thrombosis and Activated Protein C Resistance

BACKGROUND Activated protein C resistance (APC-R) due to factor V Leiden has recently been established as an important risk factor for cerebral venous thrombosis (CVT). The clinical significance of abnormal or borderline functional APC-R in the absence of factor V Leiden is uncertain. Our observations suggest that APC-R due to mechanisms other than factor V Leiden may also contribute to the development of CVT. CASE DESCRIPTIONS We describe three women who had superior sagittal and lateral sinus thrombosis while taking oral contraceptives and had a number of additional risk factors for CVT. Each had APC-R for different reasons. CONCLUSIONS Inherited thrombophilia, including APC-R, should be looked for in all patients with CVT. Functional APC-R is a highly prevalent coagulopathy, but the reasons for this abnormality are diverse; abnormal and borderline functional APC-R results should be supplemented by DNA analysis for the presence of factor V Leiden.

Cerebral venous thrombosis due to heparin-induced thrombocytopenia.

A patient with polycythemia vera who was treated with heparin for superficial septic thrombophlebitis developed heparin-induced thrombocytopenia and cerebral venous thrombosis with superior sagittal sinus occlusion 11 days after the institution of heparin therapy. We suggest that the severe thrombotic response to the heparin-induced platelet disorder in this patient occurred because the polycythemia vera and the purulent infection enhanced the thrombophilia caused by heparin-induced thrombocytopenia. This condition can be avoided in most instances if heparin is used for no longer than 5 days.

A model for the treatment of cancer pain

Abstract Previous suggested protocols for the management of cancer pain have focused solely on the use of systemic analgesics. Studies of other modalities of pain management have reported the effectiveness of single methods of therapy (such as nerve blocks or surgical ablation). In response to the increasing recognition that cancer pain may be difficult to manage with any single-modality therapy, we used an expert (or consensual) panel method to propose how multiple therapies (analgesics, neuroablative procedures, and other non-drug therapies) might be combined in the management of patients with progressive pain. The product of this method is a decision tree suggesting the steps at which to consider various combined therapies dependent upon response to prior treatment. The decision tree is expected to have utility as an educational tool as well as a basis for generating testable hypotheses about the effectiveness of combined therapies for future clinical research.

Cerebral venous thrombosis with plasminogen deficiency.

We describe a patient with inherited plasminogen deficiency who developed extensive cerebral venous thrombosis. Several other conditions that might have contributed to a hypercoagulable state, including mild thrombocytosis, thyrotoxicosis, and a chronic inflammatory lung disorder, were present. We also discuss the evidence linking plasminogen deficiency with a thrombophilic state. The diagnosis of cerebral venous thrombosis in this case was readily established by nuclear magnetic resonance imaging, a technique that is ideally suited for the evaluation and follow-up of patients with this condition.

'Eight - Drugs -in -One- Day ' ' Chemotherapy Administered Before and After Radiotherapy to Adult Patients With Malignant Gliomas

Thirty‐one adult patients with malignant glioma (23 with glioblastoma multiforme, six with anaplastic astrocytoma, and two with brainstem glioma) were treated with up to ten cycles of “eight‐drugs‐in‐one‐day” chemotherapy (methylprednisolone 300 mg/m2, vincristine 1.5 mg/m2 [maximum of 2 mg/cycle], CCNU 75 mg/m2, procarbazine 75 mg/m2, hydroxyurea 3000 mg/m2, cisplatin 90 mg/m2, cytosine arabinoside 300 mg/m2, and imidazole carboxamide 150 mg/m2). Chemotherapy was planned as two cycles before and eight cycles after 60 Gy of involved brain irradiation. A total of 117 cycles of chemotherapy was administered. There was one treatment‐related death. Myelosuppression was the most frequent toxic effect (leucopenia was < 1000/mm3 in 9% of cycles and 1000–2500/mm3 in 25%; thrombocytopenia was < 100,000/mm3 in 33% of cycles). Sixteen patients developed infections requiring treatment, two of which were life‐threatening. Five patients suffered ototoxicity. Nausea and vomiting were observed in 35% of patients. A reversible rise in creatinine was observed in five patients. One patient developed a severe motor neuropathy, and three patients developed mild peripheral neuropathies. Three patients had episodes of atrial fibrillation. One new bundle branch block with supraventricular tachycardia was observed in a patient with pulmonary embolus. Five patients developed thrombophlebitis, three of whom had pulmonary emboli. Two patients suffered strokes in areas anatomically separate from their tumor. Eleven patients declined to continue therapy after receiving an average of three cycles. Two had complete, and five had partial responses. The median survival time was 47 weeks. The responses and survival times observed are comparable to less toxic treatment protocols for adults with malignant gliomas.

Sarcoidosis of the spinal cord with extensive vertebral involvement: A case report

We report on a patient with systemic sarcoidosis who was presented with myelopathy and backache. Plain spinal films were normal, CT scan showed sclerotic lesions within the vertebrae. MRI showed more extensive involvement of the spine with multiple vertebral lesions which were hypointense on both T1W1 and T2W1 and did not enhance with gadolinium. MRI also showed high signal lesions within the cervical and lumbar spinal cord on T2-weighted images (T2W1) which were isointense on T1-weighted images (T1W1) and did not enhance. Vertebral biopsy results were consistent with the diagnosis of sarcoidosis. MRI is very sensitive in detecting sarcoidosis of bone but non-specific and other types of sclerotic or lytic bone lesions (notably metastases) need to be excluded.

Trisomy 16 mice: neural, morphological, and immunological studies

The occurrence of trisomy (i.e, the presence of an additional chromosome in the genome) is associated with distinct and deleterious effects on the development and cellular processes of affected individuals. Efforts are now directed toward understanding the mechanisms by which the trisomic condition causes adverse effects. Trisomy for autosome number 21, Down’s syndrome, is of particular interest because of its high frequency (1 in 700 live births), the associated mental retardation, and the observation that individuals with the condition survive to the fourth and fifth decades. The Down syndrome has been the single most extensively investigated entity involving mental retardation since it was first identified in the middle of the 19th century.’,* The discovery of the chromosomal basis of Down’s syndrome in 19593 provided the initial impetus to relate specific phenotypic effects with cellular processes that are altered by the presence of the additional genetic material. Such studies have included: ( 1 ) detailed characterizations of Down’s syndrome morphologic phen~type;~,’ (2) identification of gene dosage phenomena for genes located on chromosome 21 (e.g., superoxide dismutase I); and ( 3 ) observations of possible effects of trisomy on cell proliferation.6 An extension of this work is now possible using trisomic mice that can be generated by using males or females with appropriate Robertsonian translocation ch rom~somes .~ The trisomy for murine autosome 16 is of interest because murine chromosome 16 contains several genes that are present in human chromosome 21. The shared genes include those coding for superoxide dismutase-1 , the alpha and beta interferon receptors, and the response of cells to beta-adrenergic agonist s t im~la t ion .~ .~ Three of these genes code for cell surface receptor linked systems. As with the Down’s syndrome, gene dosage effects also occur for the gene products of these loci in the trisomic mice. A difficulty with the trisomy 16 system is that none of these mice survive beyond term with breeding schemes that have been used so far.I0 Our current investigations include an evaluation of the effects of the additional chromosome 16 on the expression of cell surface markers, (e.g., the major histo-

Morgagni on Apoplexy in De Sedibus: A Historical Perspective

This paper considers the historical significance of case reports on apoplexy and paralysis in Morgagnis De Sedibus et Causis Morborum. When autopsies became relatively common in the sixteenth century, Galens speculation that apoplexy was caused by the accumulation of cold phlegm or black bile in the cerebral ventricles began to be questioned and was largely abandoned in the following century. The notion that the seats and causes of diseases are to be found in solid organs and not in the dyscrasia of humors gradually replaced many but not all humoral concepts. Morgagnis letters on apoplexy bolstered this “solidist” idea, but humoral physiology was still employed as a foundation for the treatment of apoplexy and to explain some aspects of the pathogenesis of this syndrome. Based on autopsy studies, Morgagni considered two principal forms of apoplexy, due to intracranial hemorrhage (“sanguineous apoplexy”) and excessive intracranial fluid (“serous apoplexy”), to which he added a group that he judged to be separate from these two archetypes.

Differentiation of Acute Cortical and Subcortical Ischemic Stroke by Risk Factors and Clinical Examination Findings

Background: Differentiation between acute cortical and subcortical ischemic stroke may be problematic when cortical stroke presents without obvious cortical deficits such as aphasia, neglect or hemianopia. This study explores stroke risk factors and clinical variables that may assist in this differentiation. Methods: Records of consecutive patients with acute ischemic stroke, examined within 72 h of symptom onset, were reviewed. Stroke type was verified by clinical course and follow-up imaging. Stroke risk factors and acute examination findings were compared by odds ratios and positive predictive values for cortical and subcortical stroke. Results: For 355 patients studied, 237 had cortical stroke and 118 had subcortical stroke. Odds ratios for cortical stroke were highest for atrial fibrillation by EKG (OR = 4.77, CI = 2.08–10.94), recent hospitalization (OR = 4.51, CI = 2.39–8.53) and nonalert mental status (OR = 4.50, CI = 2.29–8.87). Possible cardioembolic condition, ischemic heart disease and peripheral vascular disease were also significant, but hypertension, age and diabetes mellitus were not significantly different for the stroke subtypes. Cortical deficits were absent in 19.4% of cortical stroke patients on initial examination. Predictive models were generated based on the presence or absence of cortical deficits and the interaction of significant risk factors with degree of motor deficit. Conclusions: There are clinical features that, in addition to initial examination, may help differentiate cortical from subcortical ischemic stroke. These features may be relevant to both diagnostic and therapeutic approaches to acute stroke.