Polymer coating embolism from intravascular medical devices

The deaths of at least three people who had hospital procedures in Vancouver were caused by coatings that sloughed off medical devices like catheters and scattered through blood vessels to major organs, a recent study has found. Here's a link to the relevant news article.

Rupal I. Mehta, MD

Thanks to Dr. Rupal I. Mehta of the University of Rochester for alerting me to this article. Dr. Mehta herself has published on this increasing recognized phenomenon. Here's a link to her update on the topic.

Dr. Harry Vinters had this to say about the new study coming out of Canada: “Their study is especially intriguing in that it utilizes what could be considered old technology — careful tissue analysis of autopsy specimens — to derive extremely important new information that has a direct impact on outcomes in a select group of patients. Indeed, the autopsy is about the only way this data could have been derived, and Dr. Maguire and his colleagues are to be congratulated for the care with which the study was performed and the data analyzed.” Dr. Vinters has published on this topic as well. Here is a link to his review.

CLIPPERS: chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids

These lesions histologically demonstrate a lymphocytic perivascular inflammatory pattern 

Diffuse intracranial dolichoectasia in a 68 yo man with thoracic arterial dissection

Picture courtesy of Mark Cohen, MD of Case Western Reserve University

Best Post of April 2018: Exuberant endothelial reactive hyperplasia next to a subacute infarct biopsied to rule out neoplasia

The next is on "Best of the Month" series is from Tuesday, April 3, 2018:

Endothelial hyperplasia next to an infarct, not to be confused with microvascular proliferation in a glioma

Exuberant endothelial reactive hyperplasia next to a subacute infarct biopsied to rule out neoplasia

Endothelial hyperplasia next to an infarct, not to be confused with microvascular proliferation in a glioma

Choroid plexus hemorrhage mimicking an intraventricular neoplasm in a newborn

Imaging yielded a differential diagnosis of embryonal tumor, ependymoma, and hemorrhagic choroid plexus papilloma. Histomorphology shows acute hemorrhage and hemosiderin-stained choroid plexus with a rounded, hobnail-shaped epithelial surface. The rounded surface distinguishes this normal choroid plexus from the epithelium of a choroid plexus papilloma, which has a flat surface.

Best Post of November 2015: A 60-year-old woman with a left occipitotemporal brain lesion

The next in our "Best of the Month" series comes from November 18, 2015:

We were sent this case in consultation to rule out infiltrating neoplasm. The diagnosis is amyloid beta related angiitis (ABRA). In this case, no infarction was present in the specimen, but white matter rarefaction (the presumed pathologic correlate to the leukoaraiosis reported on imaging) is present.

Granulomatous vasculitis associated with pink hyaline material in vessel walls

The pink hyaline material is shown to be beta-amyloid by immunohistochemistry

White matter rarefaction (upper half of picture) correlating with leukoaraiosis seen on imaging

A 60-year-old woman with a left occipitotemporal brain lesion

We were sent this case in consultation to rule out infiltrating neoplasm. The diagnosis is amyloid beta related angiitis (ABRA). In this case, no infarction was present in the specimen, but white matter rarefaction (the presumed pathologic correlate to the leukoaraiosis reported on imaging) is present.

Granulomatous vasculitis associated with pink hyaline material in vessel walls

The pink hyaline material is shown to be beta-amyloid by immunohistochemistry

White matter rarefaction (upper half of picture) correlating with leukoaraiosis seen on imaging

A Primer on Perinatal Telencephalic Leukoencephalopathy

In my last post, it was correctly pointed out by two astute readers that the Netter figure demonstrating brain malformations included an entity which is NOT a brain malformation: perinatal telencephalic leukoencephalopathy (PTL). PTL results from a perinatal hypoxic insult and is not a malformation per se, as the term "malformation" should really be reserved for anatomic abnormalities resulting from developmental defects. The cerebral white matter in the fetus and neonate is particularly susceptible to injury as it is metabolically highly active. Ischemia of the germinal matrix, subependymal region, and periventricular white matter can lead to periventricular leukomalacia that may even calcify and result in periventricular mineralization (1). At its most extreme, PTL may take the form of hemispheric multicystic leukomalacia in which the cerebral hemispheric white matter is replaced by multiloculated cysts separated by strands of fibroglial tissue.(2)

References:
1. Fuller, Gregory N. and Goodman, J. Clay. Practical Review of Neuropathology. Lippincott 2001. Page 315.
2. Haberland, Catherine. Clinical Neuropathology: Text and Atlas. Demos Publishing 2007. Page 303.

Treatable Neurological Disorders Misdiagnosed as Creutzfeldt-Jakob Disease

A case of primary CNS angiitis thought to be sCJD

Dr. Mark Cohen and a team of workers at Case Medical Center in Cleveland, Ohio have published an important article in the Annals of Neurology entitled Treatable Neurological Disorders Misdiagnosed as Creutzfeldt-Jakob Disease (Ann Neurol 2011;70:437–444). Why is this article important? Well, because mistaking a survivable, treatable disorder for a fatal, non-treatable disorder is not optimal. Cohen's team reviewed the pathologic diagnoses of 1,106 patients who were referred for potential prion disease to the National Prion Disease Pathology Surveillance Center (NPDPSC) at Case Western Reserve University from 2006 to 2009. About one-third of the cases did not have prion disease, with Alzheimer disease and vascular disease being the most common conditions accounting for dementia. Further, about one-quarter of the non-prion cases had treatable diseases, including immune-mediated disorders, neoplastic disorders such as lymphoma, as well as infectious and metabolic disorders. The immune-mediated disorders included primary angiitis of the CNS, acute disseminated encephalomyelitis, limbic encephalitis, neurosarcoidosis, paraneoplastic cerebellar degeneration, and one case of Wegener granulomatosis. Of note, more than half of patients with a treatable dementia had a positive CSF 14-3-3 protein test, highlighting the danger of relying too heavily on this test in making a diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD). It turns out that the most specific test for distinguishing CJD from other diseases was magnetic resonance imaging. Drs. David Perry and Michael Geschwind, in a review of this study in the September 2011 issue of Nature Reviews Neurology, (Perry, D. C. & Geschwind, M. D. Nat. Rev. Neurol. 2011:7, 479–480) write: "The fact that many of the non-prion diagnoses in the present study were potentially treatable RPDs [rapidly progressive dementias] should prompt thorough diagnostic testing in patients who are suspected of having sCJD, in order to rule out mimics. The use of CSF testing, contrast-enhanced MRI, and autoimmune antibody screening is supported by this study."

An unusual case of CADASIL? Or something else?

I recently did a brain autopsy on a 70-year-old woman who died from an intraparenchymal brain hemorrhage after a seven-year history of progressive dementia. The gross photograph (provided by Chad Jeffers, Memorial Medical Center, Springfield, IL)  follows:

I know what you're thinking: an amyloid angiopathic bleed, or perhaps a hypertensive bleed, in a patient with Alzheimer disease. That's what I was thinking until I saw in the chart that abnormal white matter changes on MRI prompted the neurologist to order Notch3 genetic testing on the patient, which surprisingly came back positive for a mutation. The patient therefore carried a clinical diagnosis of Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL), despite the fact that she had no clear family history indicative of this disease and despite the advanced age of symptom onset. At autopsy, there was no evidence of amyloid angiopathy on Congo red stain. She did appear to have the PAS-positive vessel wall deposits that would be consistent with a diagnosis of CADASIL (see photomicrographs below).  Plus, it is hard to refute a positive genetic test. The Notch3 test has excellent specificity, from what I hear. Although one does not typically think of intracranial hemorrhage in the context of CADASIL, a series out of Korea (Choi JC et al. Neurology 67(11), 12 December 2006, pp 2042-2044) found that 25% of their symptomatic patients with CADASIL had intracranial hemorrhage (ICH). If anyone has any other ideas about what might be the diagnosis in this case, I would love to hear from you.

Best Post of Sept '08: Extramedullary hematopoesis is not an uncommon finding in subdural hematomas

The next in my "Best of the Month" series, in which I feature my favorite post from each month, is from September 26, 2008:

I received a case in consultation this week from a general pathologist who was concerned about clusters of unusual-looking cells within a chronic subdural hematoma (SDH), a specimen the surgeons call a "subdural membrane" (look at the picture above of a resected chronic subdural hematoma from Greenfield's textbook to see why surgeons use that term). I felt that the cluster of cells represented foci of extramedullary hematopoesis (EMH). Another general pathology colleague was doubtful that such a phenomenon was likely in an patient with no other hematological disorders. I countered that perhaps 25% of SDH cases in hematologically intact patients show EMH. This prompted an email to the illustrious Hopkins neuropathologist Peter Burger (pictured), who provided me with a reference to an 2007 article by Juan Rosai and colleagues. In their article, Rosai and friends cited a larger study by Muller et al. (reference 1) in which "a microscopic study of 130 chronic subdural hematomas... found nucleated red blood cells in 41 cases (32%). In a subsequent study, the same authors found erythroblasts in 33% of 38 cases, and this percentage increased to 57% after serial sections were taken." The Rosai article itself (reference 2) describes in detail two cases with the aim of documenting the fact that "such lesions can fool the 'general' surgical pathologists, including some who can hardly be regarded as 'junior'."

References:

1. Muller W, Zimmermann E, Firsching R. Erythropoiesis in chronic subdural hacmatomas. Acta Neurochir (Wien). 1988;93:137-139.

2. Kuhn E, Dorji T, Rodriguez J, Rosai J. Extramedullary Erythropoiesis in Chronic Subdural Hematoma Simulating Metastatic Small Round Cell Tumor. International Journal of Surgical Pathology 15:3 [July 2007] p.288-291.

Extramedullary hematopoesis is not an uncommon finding in chronic subdural hematomas

I received a case in consultation this week from a general pathologist who was concerned about clusters of unusual-looking cells within a chronic subdural hematoma (SDH), a specimen the surgeons call a "subdural membrane" (look at the picture above of a resected chronic subdural hematoma from Greenfield's textbook to see why surgeons use that term). I felt that the cluster of cells represented foci of extramedullary hematopoesis (EMH). Another general pathology colleague was doubtful that such a phenomenon was likely in an patient with no other hematological disorders. I countered that perhaps 25% of SDH cases in hematologically intact patients show EMH. This prompted an email to the illustrious Hopkins neuropathologist Peter Burger (pictured), who provided me with a reference to an 2007 article by Juan Rosai and colleagues. In their article, Rosai and friends cited a larger study by Muller et al. (reference 1) in which "a microscopic study of 130 chronic subdural hematomas... found nucleated red blood cells in 41 cases (32%). In a subsequent study, the same authors found erythroblasts in 33% of 38 cases, and this percentage increased to 57% after serial sections were taken." The Rosai article itself (reference 2) describes in detail two cases with the aim of documenting the fact that "such lesions can fool the 'general' surgical pathologists, including some who can hardly be regarded as 'junior'."

References:

1. Muller W, Zimmermann E, Firsching R. Erythropoiesis in chronic subdural hacmatomas. Acta Neurochir (Wien). 1988;93:137-139.

2. Kuhn E, Dorji T, Rodriguez J, Rosai J. Extramedullary Erythropoiesis in Chronic Subdural Hematoma Simulating Metastatic Small Round Cell Tumor. International Journal of Surgical Pathology 15:3 [July 2007] p.288-291.

What is the second most common cause of dementia?

In a lecture delivered at the 2008 American Academy of Neurology meeting, Dr. Helena C. Chui, chair of neurology at UCLA, posed the following question: What is the second most common cause of dementia after Alzheimer disease? Her answer was that if you are talking about a primary neurodegenerative disease, it’s Dementia with Lewy Bodies. If, however, you are talking about any kind of dementia, vascular dementia takes the number two spot. The problem from the neuropathologist’s point of view is that it is difficult to arrive at criteria for the diagnosis of vascular dementia. Do four infarcts give you vascular dementia? Seven? It depends, of course, upon where those infarcts are located. Theoretically, a single infarct in the thalamus can result in dementia. All the neuropathologist can really do is list the locations and sizes of the infarcts identified at autopsy and let the neurologist make the call as to whether or not the patient’s dementia is due to a vascular cause.

The mechanism of post-traumatic cerebral fat emboli

I was giving a lecture on the pathology of cerebrovascular disease today, and showed a picture from Robbins of a brain with a shower of fat emboli after fracture of long bones. A student asked what the mechanism would be, pointing out that it would be difficult for marrow fat to get from the venous system of the leg into the arterial circulation of the brain without going through the filter of the pulmonary capillary bed.

The etiology of fat emboli after trauma is not clear. According to an article by Butteriss et al. in the American Journal of Neuroradiology, microemboli may pass into the systemic circulation either via cardiac or intrapulmonary right-left shunts or directly through the pulmonary capillary bed. Apparently a study of orthopedic surgery in dogs has shown that fat globules of <5 µm can traverse the pulmonary micovasculature. One could imagine these globules coalescing in the brain and causing significant infarcts, I suppose.

Whatever the mechanism, I imagine air emboli introduced when inserting or pulling out a central line might form in a similar manner.

(Source: D.J.A. Butteriss et al., Reversible Cytotoxic Cerebral Edema in Cerebral Fat Embolism . American Journal of Neuroradiology 27:620-623, March 2006.)

Natural History of vertibrobasilar dolichoectasia

Vertibrobasilar dolichoectasia (VBD) is enlargement, elongation, and tortuosity of the basilar artery. Passero and Rossi have an article in the current issue of Neurology discussing the natural history of this condition. The outcomes from VBD ranges from completely asymptomatic to compression of the brainstem or cranial nerves, obstructive hydocephalus, ischemia in the vertibrobasilar artery distribution, and intracranial bleeds of various kinds. So the natural history depends on the condition at diagnosis and on its evolution. (Source: Passero SG and Rossi S. 'Natural history of verterbrobasilar dolichoectasia' Neurology, Jan 1, 2008. Vol 70, number 1. Pages 66-72).

Primary Angiitis of the CNS: The Elvis Presley of Neurology

Dr. David Hellmann of Johns Hopkins, in the current Clinical Neurology News, is quoted as saying that primary angiitis of the central nervous system (PACNS) “is the Elvis Presley of neurology… CNS vasculitis-like illness is more often thought to be present than actually present”. In fact, he says, CNS vasculitis accounts for only 1% of all biopsy-proven cases of vasculitis. Interestingly, very few patients with PACNS describe a stroke-like presentation. Rather, the most common presentation is insidious cognitive decline with headache. A biopsy is required for diagnosis, and cyclophosphamide without a definitive biopsy-proven diagnosis is not recommended. Yet again, the neuropathologist is the key!