A 38-year-old HIV-infected patient presenting with seizures

The Diagnostic Slide Session at the recent American Association of Neuropathologists annual meeting in Philadelphia featured a fascinating case by Dr. Sandra Camelo-Piragua, Ronald A. Goerss, and David N. Louis of Massachusetts General Hospital. The case was that of a 38-year-old AIDS patient who had been only intermittently compliant with his HAART therapy. He presented to the hospital with seizures in 2009 after a year of fluctuating neurological symptoms. Imaging studies showed the following white matter changes:

Biopsy showed a marked lymphocytic infiltrate, which included diffuse, perivascular, and follicular arrangements:

Macrophages were also present:

The following stains for organisms were all NEGATIVE: AFB, GMS, HSV1, HSV2, CMV, HHV8, and toxoplasma. An H&E/LFB stain demonstrated that this was a leukoencephalopathic process:

Immunohistochemistry of one of the lymphoid follicles indicated that the lymphoid infiltrate was a reactive, rather a neoplastic process:

Polyoma virus immunohistochemistry for the SV40 (a surrogate marker for JC virus due to cross-reactivity) was found to be positive:

So, the final diagnosis rendered was Progressive Multifocal Leukoencephalopathy (PML) with concomitant Immune Reconstitution Inflammatory Syndrome (IRIS). IRIS is an inflammatory response in HIV-infected individuals upon initiation of HAART therapy. The immune response can be so robust as to cause morbidity, particularly with the brain is involved. Thanks to Dr. Camelo-Piragua for providing the images associated with this interesting case, and I wish her the best of luck in her upcoming move to Ann Arbor where she will take a position on the faculty at the University of Michigan!

Sleepless

Neuropathologist Henry Brown, MD, PhD (pictured) recommends the novel Sleepless by Charlie Huston to those in the neuropathology community with an interest in the fatal insomnias. A review on Amazon.com describes the book as a "thriller set in a postapocalyptic Los Angeles, [where] a devastating illness renders the afflicted unable to sleep. In about a year, those with SLP (as the sleepless illness is known) deteriorate and die." Dr. Brown says that the novel may be "a little out there for some of our neuropathologists, perhaps", but a good read nonetheless.

2010 AANP Diagnostic Slide Session diagnoses revealed

For those of you who missed this evening's diagnostic slide session, here are the diagnoses that were ultimately revealed:

1. Phosphaturic mesenchymal tumor, mixed connective tissue variant
2. Primary Solitary Amyloidoma
3. CNS parenchymal involvement by Kikuchi-Fujimoto disease
4. Teratoma with malignant transformation
5. Progressive Multifocal Leukoencephalopathy with Immune Reconstitution Inflammatory Syndrome
6. Varicella Zoster Virus meningitis with intraparenchyal hemorrhage
7. Aneurysmal hemorrhage due to isolated intracranial giant cell arteritis
8. Canine distemper viral encephalitis in a Bengal tiger
9. Feline spinal cord leukomyelopathy secondary to consumption of irradiated dry food diet
10. Acute Hemorrhagic Leukoencephalitis (Weston Hurst disease)
11. Frontotemporal lobar degeneration with ubiquitin proteasome system inclusions (FTLD-UPS) with cerebellar involvement
12. Neimann Pick type C1 disease (compound heterozygote)

As you can see, it was the usual array of simple diagnoses!!!

Two more neuropathology job opportunities listed on announcement board at annual AANP meeting

Dr. Harry Vinters (pictured), in a conversation I just had with him in the refreshment area at the annual AANP meeting, told me that when a trainee complains about the paucity of jobs in neuropathology, he simply refers them to Neuropathology Blog! As you can see in the job listings section of this blog, opportunities for clinical neuropathologists are abundant -- as long as you are willing to relocate. I just checked the announcements bulletin board at the meeting, and discovered two new jobs that I am only now adding to the blog job posting list. Dr. Adekunle Adesina at Texas Children's Hospital/Baylor College of Medicine is looking for a neuropathology faculty member. He can be reached at amadesin@texaschildrens.org. Also, Dr. Steven Chin of the University of Utah in Salt Lake City is seeking a neuropathologist at the assistant or associate level. Dr. Chin can be reached at steven.chin@path.utah.edu. Happy hunting!

86th Annual AANP Meeting: Rapamycin as a possible treatment for tuberous sclerosis

Drs. David Louis (AANP president) and Anat Stemmer-Rachamimov put together a nice day-long educational session today to kick off the American Association of Neuropathologists annual meeting here in Philadelphia. In addition to our own kind, non-neuropathologists were brought in to give their persepctives on these syndromes. For instance, Dr. Elizabeth Henske (pictured), an oncologist, talked about the spectrum of clinical manifestations seen in tuberous sclerosis complex (TSC) and experiemental therapeutics based on understanding the molecular underpinnings of the syndrome. Given that the genes mutated in tuberous sclerosis (TSC1 and TSC2) inhibit mTOR, Henske said that researchers are looking into the use of rapamycin, an inhibitor of mTOR, as a treatment for not only the more obvious manifestations of TSC, such as subependymal giant cell astrocytoma, but even for reversing learning deficits in children with TSC. In a mouse model of TSC in which there is no pathological evidence of brain lesions, it was discovered that these mice have cognitive defects as evidenced by water-maze testing. "And the thing that just gives me shivers to think about," says Henske, "is that these cognitive deficits are correctable with rapamycin. Five days of rapamycin! So that has caused a big shift in the thinking about children with tuberous sclerosis who have cognitive defects and many parents are actually putting their children on rapamycin off-trial, but we would really like to do a cognitive trial and figure out whether there is benefit in children with tuberous sclerosis who are taking rapamycin. The parents, many of them, have very compelling anecdotal studies of improvement in their childrens' learning or behavior." Therefore, Dr. Henske will be working on an efficacy and safety trial, with funding from the Tuberous Sclerosis Alliance, to see if rapamycin can improve cognitive function in these children. "If there is benefit with rapamycin neurocognitively, it would just be wonderful."

American Association of Neuropathologists happens next week

The American Association of Neuropathologists' annual meeting will be held in Philadelphia next week -- from June 10 to June 13. I'll be there -- blogging live -- with comments from participants, summaries of cutting-edge presentations, and news from the world of neuropathology.  Among the offerings will be a lecture on Autoimmune Synaptic Encephalitis by Dr. Josep Dalmau (pictured) of the University of Pennsylvania. Numerous other presentations are planned, including the Presidential Symposium, entitled: "Big Science" and the Transition to Personalized Medicine: How Can Neuropathologists Play a Role in Large-Scale Clinical, Translational and Basic Research?  I myself will appear at a panel on Friday the 11th at the trainee luncheon, where I'll be talking about landing your first job. I'll be joined on the panel by Dr. Suzanne Z. Powell who will discuss neuropathology training and Dr. Tony Yachnis who will talk about mentorship and sustainability. I look forward to the event and to meeting a few Neuropathology Blog readers along the way!