Lisch nodules in a patient with NF-1

A. Multiple tan or pale brown dome-shaped nodules on surface of iris of patient with NF-1. Lisch nodules occur in nearly all affected adults with neurofibrosis, type 1. B. Focus of partially pigmented cells rests on anterior iridic surface. Lisch nodules are melanocytic hamartomas.

From: Eagle, Ralph C. Jr.. Eye Pathology: An Atlas and Text. Second Edition (2011). Page 20.

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."

Best Post of December '07

This post was an answer to a quiz question posed on the previous day:

From what disease did "the Elephant Man" suffer?

Joseph Merrick was originally thought to be suffering from neurofibromatosis type I, a genetic disorder also known as von Recklinghausen's disease. However, it was postulated in 1986 that Merrick actually suffered from Proteus syndrome (a condition which had been identified by Michael Cohen seven years earlier). Unlike neurofibromatosis, Proteus syndrome (named for the shape-shifting god Proteus) affects tissue other than nerves, and is a sporadic rather than familially transmitted disorder. In July 2003, Dr. Charis Eng announced that as a result of DNA tests on samples of Merrick's hair and bone, she had determined that Merrick certainly suffered Proteus syndrome, and may have had neurofibromatosis type I as well. (The above information is adapted from the wikipedia article. But citations are provided.)

The clinical manifestations of Proteus syndrome are, as the name implies, protean. They include: partial gigantism of hands or feet; hemihypertrophy; subcutaneous lipomas; multiple nevi; areas of thickened skin and subcutaneous tissue; macrocephaly; skull anomalies; and accelerated growth in long bones. Mentation can be normal or retarded.

Answer to Quiz Question

Joseph Merrick was originally thought to be suffering from neurofibromatosis type I, a genetic disorder also known as von Recklinghausen's disease. However, it was postulated in 1986 that Merrick actually suffered from Proteus syndrome (a condition which had been identified by Michael Cohen seven years earlier). Unlike neurofibromatosis, Proteus syndrome (named for the shape-shifting god Proteus) affects tissue other than nerves, and is a sporadic rather than familially transmitted disorder. In July 2003, Dr. Charis Eng announced that as a result of DNA tests on samples of Merrick's hair and bone, she had determined that Merrick certainly suffered Proteus syndrome, and may have had neurofibromatosis type I as well. (The above information is adapted from the wikipedia article. But I can vouch for its authenticity.)

The clinical manifestations of Proteus syndrome are, as the name implies, protean. They include:
- Partial gigantism of hands or feet
- Hemihypertrophy
- Subcutaneous lipomas
- Multiple nevi
- Areas of thickened skin and subcutaneous tissue
- Macrocephaly
- Skull anomalies
- Accelerated growth in long bones
- Mentation can be normal or retarded

Quiz Question

From which of the phakomatoses did Joseph Merrick (played by John Hurt in the movie 'Elephant Man') suffer? The answer will appear in tomorrow's posting.