An early regional experience with expansion of Milan Criteria for liver transplant recipients.

The Milan Criteria (MC) showed that orthotopic liver transplantation (OLT) was an effective treatment for patients with nonresectable, nonmetastatic HCC. There is growing evidence that expanding the MC does not adversely affect patient or allograft survival following OLT. The adult OLT programs in UNOS Region 4 reached an agreement allowing lesions outside MC (one lesion <6 cm, ≤3 lesions, none >5 cm and total diameter <9 cm-[R4 T3]) to receive the same exception points as MC lesions. Kaplan-Meier curves and log-rank tests were used to compare survival data. Chi-squared and Mann-Whitney U tests were used to compare patient data. A p-value of <0.05 was considered significant. All statistical analyses were performed on SPSS 15 (SPSS, Chicago, IL). Four hundred and forty-five patients were transplanted for HCC (363-MC and 82-R4 T3). Patient demographics were found to be similar between the two groups. Three year patient, allograft and recurrence free survival between MC and R4 T3 were found to be 72.9% and 77.1%, 71% and 70.2% and 90.5% and 86.9%, respectively (all p > 0.05). We report the first regionalized multicenter, prospective study showing benefit of OLT in patients exceeding MC based on preoperative imaging.

Female-to-female transmission of human immunodeficiency virus.

We describe a case of female-to-female transmission of human immunodeficiency virus (HIV). A 20-year-old African American woman with no obvious risk factors received a diagnosis of HIV infection, and the genotype of the infecting strain closely matched that of the strain infecting her openly bisexual female partner. The route of transmission was probably use of sex toys, used vigorously enough to cause exchange of blood-tinged body fluids.

Parkinsonism associated with autosomal dominant bilateral striopallidodentate calcinosis.

Bilateral striopallidodentate calcinosis (BSPDC, also known as Fahr's disease, a misnomer), is a rare disorder where bilateral, almost symmetric, calcium and other mineral deposits occur in subcortical nuclei and white matter. Neurological manifestations vary but movement disorders are the most common. Of the movement disorders, parkinsonism predominates. We describe 6 patients with BSPDC associated with parkinsonism. Of the 6 patients, one patient from an autosomal dominantly inherited family who responded to levodopa, showed Lewy bodies in substantia nigra neurons and changes consistent with BSPDC. Another patient, from the same family with clinical evidence of parkinsonism and radiological and neuropathological evidence of BSPDC, did not show Lewy bodies. Ten patients with BSPDC and parkinsonism (without evidence of parathyroid dysfunction) were found in the literature. When parkinsonism is associated with dementia and cerebellar signs, obtaining a CT scan may be helpful as BSPDC often presents with the above three conditions.

Immune thrombocytopenia: a rare presenting manifestation of tuberculosis.

We report the case of a 49 year-old male who presented with immune thrombocytopenia (ITP)-induced epistaxis and generalized purpura. During the same hospitalization the patient was also found to have clinical, microbiological, histological, and roentgenographic evidence of disseminated mycobacterial tuberculosis (TB). The hematological and infectious abnormalities, which did not respond to high-dose intravenous corticosteroids and immune globulin (IVIg), resolved after anti-tuberculous treatment. Herein we review the characteristics of this rarely documented association.

Pentagon copying is more impaired in dementia with Lewy bodies than in Alzheimer's disease.

OBJECTIVES: In many cases the clinical differentiation of patients with dementia with Lewy bodies (DLB) from those with Alzheimer's disease (AD) has been difficult. Because many neuropsychological studies have reported greater visuospatial/constructional impairment in DLB than in AD, it was determined whether accuracy in copying the interlocking pentagons item on the mini mental state examination (MMSE) may be helpful in distinguishing patients with DLB from those with AD relatively early in the course of the dementia. METHODS: All cases of neuropathologically proved DLB and AD in the Center for Alzheimer Disease and Related Disorders brain bank were retrospectively reviewed, and the first available MMSE for each was retrieved. Only patients with MMSE scores > or = 13 were included, indicating mild to moderate dementia. The patients' copies of the interlocking pentagons were analyzed and graded as acceptable or unacceptable according to the original instructions for grading the MMSE. RESULTS: Seventeen patients with DLB and 27 patients with AD were identified for whom MMSE with copies of the interlocking pentagons were available. Two patients with DLB (MMSEs 22 and 27) drew the pentagons acceptably, by contrast with 16 of the patients with AD (MMSEs 13-28). An unacceptable copy was associated with DLB with a sensitivity of 88% and a specificity of 59% (p = 0.002). CONCLUSIONS: For patients with MMSE scores > or = 13, an inability to accurately copy the pentagons suggests that the diagnosis is more likely DLB than AD. The results confirm the work of others on visuospatial/constructional impairment in DLB and indicate that this feature may be helpful in its diagnosis.

Apolipoprotein E immunoreactivity in human and mouse olfactory bulb.

We evaluated the distribution of apolipoprotein E (apoE) immunoreactivity in mouse and human olfactory bulbs. ApoE immunoreactivity was present in the olfactory nerve and around the glomeruli. Immunoreactivity was seen in somata that appeared to be glial. No neuronal staining was seen. The apoE immunoreactivity was also present in the mouse olfactory bulb subependymal layer. The specificity of immunoreactivity was confirmed with apoE-deficient mice (apoE gene knock-out mice, apoE KO) which did not display any immunoreactivity. The presence of apoE around glomeruli and nerve suggest that apoE is associated with the continuous degeneration and regeneration processes that occur in the olfactory nerve. Experimental manipulation of the olfactory nerve may be a useful technique to determine the functions of apoE in a well-defined neural system.

Cancer treatment and growth cone-associated protein in human olfactory bulb glomeruli.

BACKGROUND: Growth cone-associated protein (GAP43) is found in growing axons and we hypothesized that systemic treatment with antineoplastic agents should disrupt regeneration of olfactory receptor cells. Disruption of regeneration should be evidenced by decreased presence of growing axons in the olfactory bulb. OBJECTIVE: To evaluate GAP43 in human olfactory bulb in normal controls and in individuals receiving treatment for neoplasms. DESIGN: Immunocytochemical studies were performed on autopsied human olfactory bulbs to identify both GAP43 and olfactory marker protein immunoreactivity. The former recognizes growing axons and the latter is a definitive marker of adult olfactory nerve. SUBJECTS: Twenty-seven subjects were evaluated. Seven had received either antineoplastic agents and/or x-irradiation of the whole head. Four subjects were young, untreated controls, 10 were age matched to the treated group, and 2 had neoplasms but did not receive antineoplastic agents or irradiation of the head. In addition, 3 subjects with end-stage renal disease were immunostained. RESULTS: Subjects treated with antineoplastic agents or x-irradiation of the whole head displayed no statistically significant loss of olfactory bulb glomeruli, but GAP43 immunoreactivity was markedly reduced in all but 1 subject (P<.32). The subjects with end-stage kidney disease showed frank loss of both GAP43 immunoreactivity and olfactory glomeruli. CONCLUSIONS: Treatment with antineoplastic agents apparently does not damage olfactory epithelium directly but inhibits growth of new axons into the olfactory bulb. This observation suggests that the quality of olfactory experience may change during the course of treatment with antineoplastic agents because the olfactory nerve is not replaced.

Hemianopsia in dementia with Lewy bodies.

OBJECTIVE: To describe the pathologic changes that caused a left homonymous hemianopsia in a patient with dementia with Lewy bodies. DESIGN: Report of a case and postmortem studies. MAIN OUTCOME AND RESULTS: A 66-year-old woman experienced parkinsonism and left homonymous hemianopsia early in the course of a rapidly progressive dementia that culminated in death only 21 months after the onset of her symptoms. Postmortem examination revealed pathologic features consistent with the diagnosis of dementia with Lewy bodies. The only apparent explanation for her visual field deficit was a disproportionately large number of neurofibrillary tangles in the right striate, peristriate, and inferotemporal cortices. CONCLUSION: A clinically obvious homonymous hemianopsia can result from the occipital and inferotemporal cortical degeneration in dementia with Lewy bodies.

The distribution of amyloid beta protein deposition in the corpus striatum of patients with Alzheimer's disease.

The distribution of amyloid beta peptide (A beta) was quantified in the corpus striatum and pallidum of 10 patients with Alzheimer's disease (AD) and three patients with both Alzheimer's disease and Parkinson's disease (AD-PD). A beta occurred almost exclusively in plaques that did not have neurites or amyloid cores. Caudate, accumbens nuclei and rostral putamen contained more of the diffuse plaques than did caudal putamen. No diffuse plaques were found in the neighbouring globus pallidus. This distribution of A beta deposition may reflect the distribution of diseased synaptic cortical afferents rather than a putative vascular source of A beta.

Onset of neurologic deficits after treatment with dihydroergotamine in a patient with sagittal sinus thrombosis.

A woman with a 7-year history of intermittent migraine had 3 months of gradually worsening headaches. Initial neurologic examination including fundus examination was normal, and initial head computerized tomographic (CT) scan and magnetic resonance imaging (MRI) were thought to be normal. The patient was given dihydroergotamine (DHE-45), 1.0 mg, intravenously for relief of headache. Five hours later, she complained of severe diffuse headache and nausea. Neurologic examination showed left arm weakness and sensory loss, blurring of the left optic disc, and bilateral Babinski signs. Cerebral arteriography demonstrated thrombosis of the sagittal sinus, which in retrospect was present on the initial contrast CT scan and MRI scan. The patient's deficits worsened, and she eventually died 20 days later as a result of cerebral infarctions and increased intracranial pressure, despite attempts at selective thrombolysis of the sagittal sinus. DHE has potent venoconstrictive effects. We suspect that DHE helped precipitate neurologic deterioration in this patient with sagittal sinus thrombosis.

Rarefied white matter in patients with Alzheimer disease.

Magnetic resonance head scans of 94 patients with probable Alzheimer disease (AD) and 45 patients with possible AD were examined prospectively to determine the prevalence and significance of rarefied cerebral white matter (leukoaraiosis) in patients with AD. Only 8.7% of patients with probable AD and 11.1% of patients with possible AD exhibited large confluent areas of subcortical leukoaraiosis. The remaining patients had variable degrees of leukoaraiosis surrounding the lateral ventricles. The magnitude of leukoaraiosis correlated with the patient's age but not with the Hachinski Ischemic and Mini Mental Status scores. Postmortem studies of two Alzheimer patients showed that their large confluent areas of subcortical leukoaraiosis consisted of rarefied white matter, gliosis, and arteriosclerotic small arteries. Eight additional Alzheimer patients who underwent autopsy had similar but less pronounced white matter changes limited to the periventricular regions of the cerebral hemispheres. Large confluent areas of rarefied subcortical white matter occur in a small minority of Alzheimer patients and are probably not caused by AD.

Pathologic changes associated with intracranial hypotension and meningeal enhancement on MRI.

We report a patient with a 6-week history of postural headache due to intracranial hypotension whose MRI revealed findings typical of this syndrome, including diffuse meningeal enhancement following gadolinium infusion. Biopsy revealed extensive fibrocollagenous proliferation in the leptomeninges without evidence of inflammation. The pathologic changes in this patient, which occurred soon after the onset of symptoms, are probably related to the striking meningeal enhancement seen in this syndrome.

Distribution of amyloid in the brainstem of patients with Alzheimer disease.

A4 protein (beta-protein, beta-amyloid) deposits were identified with silver stains in postmortem brainstem sections from 13 patients with Alzheimer disease (AD), 6 patients with mixed Alzheimer disease and Parkinson disease (AD-PD), 5 disease controls, and 2 elderly controls. A rostro-caudal gradient of A4 was found in patients with AD and AD-PD, such that A4 was most prevalent in the midbrain and least prevalent in the medulla. The brainstem of the controls contained little or no A4. The midbrain tectum and tegmentum contained the greatest densities of A4, but the red nucleus and substantia nigra pars reticulata were largely spared. This distribution of A4 suggests that A4 deposition is a function of synaptic connectivity rather than passive diffusion from vascular sources.

The open opercular sign: diagnosis and significance.

Four children with varying clinical manifestations, but with the unifying feature of severe developmental delay, had bilateral enlargement of the sylvian fissure confirmed by magnetic resonance imaging (MRI). Subsequently, we examined 125 consecutive MRI scans of the heads of pediatric patients, looking for this insular exposure, and did not find it. Pathological correlation in 1 child revealed arhinencephaly and abnormal gyral formation; another is known to have migrational abnormalities. We suggest that the open operculum is a sign of arrested development and is associated with other anomalies and a poor prognosis.

Periventricular white matter changes and dementia. Clinical, neuropsychological, radiological, and pathological correlation.

Forty-three patients with computed tomographic scan findings of decreased attenuation in the periventricular white matter (PVWM) region were studied. Clinical evaluation revealed presence of hypertension in 36 patients (84%) and cerebrovascular risk factors in 41 patients (95%). Unilateral or bilateral neurological deficits were present in 40 patients (93%). Neuropsychological evaluation in 27 of them revealed features of subcortical dementia. Magnetic resonance imaging in seven cases demonstrated high-intensity areas in the deep white matter region on T2-weighted imaging. Pathological evaluation in four patients revealed demyelination without inflammatory cells and infarctions in the PVWM region, lacunar infarctions in the basal ganglia and brain stem, and marked arteriosclerosis. The study indicated that most (95% in this series) of the patients with computed tomographic scan findings of decreased attenuation in the PVWM region had cerebrovascular risk factors and various neurological and neuropsychological features of subcortical dementia. Pathologically, these lesions represented areas of infarction and demyelination, along with diffuse arteriosclerosis.

Reevaluation of an experimental streptococcal canine brain abscess model.

An experimental cerebral abscess model in which alpha-hemolytic Streptococci were inoculated into the brain parenchyma of dogs was evaluated for assessment of antimicrobial therapy. Intracerebral ring-enhancing lesions were visualized by computerized tomography, but they resolved after time without therapeutic intervention. Histopathological study demonstrated evolution of the lesions into sterile granulomas. Quantitative cultures were performed and uniformly became sterile in the early cerebritis stage, approximately 3 days after bacterial inoculation. Therefore, this brain abscess model should not be utilized for the evaluation of new antimicrobial treatment regimens. Rather, other models which document persistent viable organisms within cerebral abscesses need to be developed.

Electroencephalographic activity after brain death.

Fifty-six consecutive patients clinically diagnosed as brain dead were seen at Loyola University Medical Center, Maywood, Ill, from January 1984 through May 1986. Eleven (19.6%) of the 56 patients had electroencephalographic (EEG) activity following the diagnosis of brain death. The mean duration of the observed EEG activity was 36.6 hours (range, two to 168 hours). Three patterns of EEG activity were observed: (1) low-voltage (4 to 20 microV) theta or beta activity was recorded in nine (16.1%) patients as long as 72 hours following brain death. Neuropathologic studies in one patient showed hypoxic-ischemic neuronal changes involving all cell layers of the cerebral cortex, basal ganglia, brain stem, and cerebellum; (2) sleep-like activity (a mixture of synchronous 30 to 40 microV theta and delta activity and 60 to 80 microV, 10 to 12 Hz spindle-like potentials) was noted in two (3.6%) patients for as long as 168 hours following brain death. Pathologic studies in both cases demonstrated ischemic necrosis of the brain stem with relative preservation of the cerebral cortex; and (3) alpha-like activity (monotonous, unreactive, anteriorly predominant, 25 to 40 microV, 9 to 12 Hz activity) was observed in one (1.8%) patient three hours following brain death. Regardless of activity on the EEG, none of the patients recovered. The occurrence of EEG activity following brain death would suggest reliance on the EEG to confirm brain death may be unwarranted. The use of the EEG as a confirmatory test of brain death may be of questionable value.

Pathologic characteristics of recurrent carotid artery stenosis.

Recurrent carotid stenosis occurs randomly in approximately 10% of patients undergoing endarterectomy. Previous studies have described several histologic features but have failed to clearly elucidate the pathogenesis of this disorder. To improve our understanding of this disease, we reviewed pathologic lesions from 20 patients with recurrent stenosis. All specimens had been fixed in formalin and were embedded in paraffin and had undergone routine microscopic studies. In addition, immunoperoxidase staining with anti-factor VIII for endothelial cells and anti-desmin and anti-actin for smooth muscle cells was performed. Recurrent stenosis had developed in 16 of the 20 specimens within 2 years of endarterectomy (early), whereas the remaining four cases occurred from 2 to 7 years after the original carotid endarterectomy (late). Endothelial cells were found lining the luminal surface of both early and late recurrent lesions. Six of sixteen early and three of four late specimens had areas of luminal surface covered with cells exhibiting immunoreactivity for anti-factor VIII. Cells showing immunoreactivity for actin or desmin and demonstrating the morphology of smooth muscle cells were found in 9 of 16 early restenotic lesions but in no late ones. Areas of endothelial cell lining of the recurrent carotid lesions in a substantial number of patients in this study represent a finding not previously described. The presence of these cells implies that a phase of the arterial healing after endarterectomy involves re-endothelialization. Contrary to previous reports, no significant role of thrombosis and/or intraplaque hemorrhage could be found to contribute to development of recurrent stenosis.(ABSTRACT TRUNCATED AT 250 WORDS)