Inflammatory hypertrophic cauda equina following intrathecal neural stem cell injection.

INTRODUCTION: Potential benefit from stem cell treatments has more patients seeking treatment without understanding possible risks. METHODS: We describe a woman who presented with progressive bilateral leg pain, numbness, and gait difficulties. A prior stroke, macular degeneration, osteoarthritis, and depression, led her to receive intrathecal neural stem cell therapy overseas 1 year before onset of symptoms. RESULTS: Imaging showed marked enlargement of lumbosacral roots of the cauda equina, which was not seen before stem cell treatment. Electrodiagnostic studies confirmed chronic multiple lumbosacral radiculopathies. Biopsy of a lumbar dorsal sensory root showed myelinated fiber degeneration and loss, with endoneurial inflammation. The hypertrophic inflammatory cauda equina syndrome was potentially triggered by the prior intrathecal neural stem cell injection. CONCLUSIONS: Safety of intrathecal stem cell treatments is not routinely regulated in overseas stem cell facilities. We wish to bring this potential complication to the attention of health care providers.

Stem cell induced inflammatory hypertrophy of the cauda equina.

Stem cell therapy can present clinicians with challenging clinical scenarios, as access to such treatments outpaces the research into their efficacy and safety due to the burgeoning trend of international travel to acquire stem cell therapy, or "stem cell tourism." Treatment of neurologic conditions remains an enticing potential application of stem cell therapy, often administered intrathecally. In response to such therapy, multiple adverse events have been described in the literature, including neoplasms, demyelinating disease, and seizures, among others. We present a case of symptomatic inflammatory cauda equina nerve root hypertrophy due to intrathecal stem cell infusion, representing a rare but significant complication.

A Patient with Noonan Syndrome with a KRAS Mutation Who Presented Severe Nerve Root Hypertrophy.

We report a 45-year-old female with clinical features resembling Noonan syndrome (NS) who presented with significant nerve root hypertrophy. She was initially diagnosed with Charcot-Marie-Tooth disease because her gait disturbance gradually deteriorated and nerve conduction velocity was reduced. However, she did not carry a PMP22 gene mutation. RASopathies are a group of phenotypically overlapping developmental syndromes caused by germline mutations that encode components of the Ras/MAPK signaling pathway. These disorders include NS, cardiofaciocutaneous (CFC) syndrome, and Costello syndrome and are associated with molecular abnormalities in the Ras/MAPK pathway. The patient was suspected to have NS and related disorders because of pulmonary artery stenosis, lymphedema, distinctive facial appearance, and intellectual disability. Genetic analysis identified a heterozygous de novo mutation in KRAS (c.211T>G, p.Tyr71Asp), which is usually observed in patients with NS or CFC syndrome. Although our patient was diagnosed with NS, she revealed clinical manifestations that were typical to CFC syndrome, including intellectual disability. It has been reported that some patients diagnosed with RASopathies with mutations in PTPN11, SOS1, or KRAS developed nerve root hypertrophy. These results suggest that nerve root hypertrophy may be associated with RASopathy, although the onset mechanisms of nerve root hypertrophy are unknown.

[Chronic inflammatory demyelinating polyradiculoneuropathy with myelopathy due to massively enlarged nerve roots].

We report a 77-year-old man who presented with numbness and weakness of the feet bilaterally, that had progressed over 13 years. He was diagnosed with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) on the basis of nerve conduction studies and a sural nerve biopsy; however, he was inadequately treated and his weakness had progressed. At 76 years of age, he developed spasticity in the legs as well as bladder and rectal incontinences. Gd-enhanced MRI revealed severe compression of the cervical cord by massively enlarged nerve roots. A cervical laminectomy was performed to decompress the cervical cord. A fascicular biopsy of the C5 dorsal root showed a prominent lymphocyte infiltration and edema. Repeated methylprednisolone pulse therapy and IVIg ameliorated the weakness. We concluded that the main cause of nerve root hypertrophy in this patient was active inflammation.