John Engstrom, MD February 14, 2020 A 61 yo man with low back pain - PDF document

John Engstrom, MD February 14, 2020 A 61 yo man with low back pain (LBP) presented to the neurology outpatient practice in December 2017 with bilateral (R > L) leg pain, weakness, numbness since April 2017. His LBP was worse with sitting and best when supine. There was no nocturnal LBP pain, fever, chills, or sweats. There was no history of head or spine trauma, MVA or whiplash, IVDU, steroid use, or cancer. There was no history of chronic infection of the lungs, skin, urinary tract, or teeth. The patient had noticed diminished bulk of his bilateral calf muscles. There was weakness when pushing off with his feet while walking up stairs or uphill. There had been no falls, but he reported occasional tripping. He reported tingling below the knees bilaterally. Meloxicam and Lyrica provided modest pain relief. Referral records provided additional information. An EMG was interpreted as showing polyneuropathy. Spinal fluid analysis revealed the following: wbc 29 (66L/34M), rbc 1325, glucose 42, and protein 165 mg/dl. Flow cytometry was negative for neoplasm. CRAG was negative. Bacterial and fungal stains and cultures were negative. The CSF results were thought to reflect a possible chronic, low grade infection. His past medical history was notable for NAION (non-arteritic ischemic optic neuropathy) that had left him legally blind in both eyes. He is a retired, college- educated citrus farmer who has traveled the world and asks good questions. On general examination, there were no straight-leg raising signs or no palpation tenderness over the lumbar spine. On neurologic examination, mental status and cranial nerve assessments (in detail) were normal. On motor examination, there was normal tone in the limbs and mildly reduced bulk in the calves and feet. FFM were normal bilaterally and pronator drift was absent. Power testing in the arms and proximal legs was normal including deltoid, biceps, triceps, IP, quads, hamstrings, leg adductors, and leg abductor muscles. Power in the distal legs (R/L) was as follows: TA 4-/4-, EHL 4-/4-, toe flexors 4/4, and peronei 5/5. Deep tendon reflexes were absent except for 1+ right biceps brachii. He walked with a slight steppage gait bilaterally, and was unable to heel or toe walk bilaterally. Sensory examination was abnormal for decreased light touch sensation distal to the knees and impaired vibration sensation at the great toes bilaterally. There was a Romberg sign present with swaying in all directions when his eyes were closed. Additional diagnostic studies were performed.

References 1. Alderazi YJ, Coons SW, Chapman K (2012). J Child Neurol. doi: 10.1177/0883073811422831 2. Amariglio N, Hirshberg A, Scheithauer BW, Cohen Y, Loewenthal R, Trakhtenbrot L, et al. (2009) PLoS Med. doi: 10.1371/journal.pmed.1000029 3. Bauer G, Elsallab M, Abou-El-Enein M (2018) Stem Cells Transl. Med. doi: 10.1002/sctm.17-0282 4. Berkowitz AL, Miller MB, Mir SA, Cagney D, Chavakula V, Guleria I, et al. (2016) N. Engl. J. Med. doi: 10.1056/NEJMc1600188 5. Hurst RW, Peter Bosch E, Morris JM, Dyck PJB, Reeves RK (2013) Muscle and Nerve. doi: 10.1002/mus.23920 .

John Engstrom, MD February 14, 2020 n-SCIPT: Case Discussion The name of the syndrome represented by this patient and the five other patients is n- SCIPT. The acronym stands for Neuroglial Stem Cell derived Inflammatory Pseudotumor. The cardinal features include primitive neuroglial tissue that encases the nerve roots or presents with a mass-like appearance. The tissue is derived from stem cells infused into the subarachnoid space and is near the site of infusion. The CSF results reveal an inflammatory profile. The appearance of the tissue raises the diagnostic possibility of a neoplasm, but the low mitotic index and other features indicate partially differentiated primitive neuroglial tissue only. The rise of loosely regulated stem cell clinics nationally and unregulated stem cell clinics internationally have given rise to mythical promises about the benefits of such infusions in the complete absence of proof. These false promises are the 21 st century equivalent of the 19 th century snake oil salesmen who promised snake oil as a panacea “for what ails you.” For example, if you perform a google search of “stem cell and blindness” you will see an extensive list of stem cell therapy options for a list price of up to $50,000 per infusion. Dr. Arnold Kriegstein, a senior stem cell scientist at UCSF and a faculty member in Neurology, has testified before congress regarding the real and potential dangers of unregulated stem cell transplantation. In common with the patient presented today, the source of the stem cells and the stem cell screening process is unclear to the patient and poorly documented. Even in the United States, allogenic stem cells may be included in these infusions about 15% of the time. No reliable information regarding these parameters is are available from international sources of stem cell infusions. As a result, we can expect to see more unusual neurologic complications of intrathecal stem cell therapy over in the future. It is important for the clinical neurologist to be aware of this syndrome for several reasons. First, we need to be comfortable telling our patients that unregulated stem cell therapy is an expensive scam. Second, we need to be prepared to give patients examples of the serious risks or complications known to be caused by unregulated stem cell therapies. Third, all our patients are susceptible to false promises of cure for untreatable illnesses. The patient presented today is an outstanding example of how this principle applies to all patients. Fourth, we need to be prepared to ask our patients if they have had stem cell therapies in the setting of thickened lumbar nerve roots and lumbar polyradiculopathy or the presence of unexplained abnormal tissue in the lumbar subarachnoid space. Many issues regarding the neurologic complications of intrathecal stem cell therapy are unresolved. The timeline over which neurologic complications of intrathecal stem cell therapy might present is unknown. The long term prognosis of n-SCIPT is unknown. The extent to which the inflammatory cerebrospinal fluid is beneficial or injurious is unknown. The utility of immunomodulation therapy is unknown. While n-SCIPT is one complication, we will almost

certainly see others. Close follow-up of these patients will further define the natural history and optimal management of N-SCIPT. References 1. Alderazi YJ, Coons SW, Chapman K (2012) Catastrophic demyelinating encephalomyelitis after intrathecal and intravenous stem cell transplantation in a patient with multiple sclerosis. J Child Neurol. doi: 10.1177/0883073811422831 2. Amariglio N, Hirshberg A, Scheithauer BW, Cohen Y, Loewenthal R, Trakhtenbrot L, et al. (2009) Donor-derived brain tumor following neural stem cell transplantation in an ataxia telangiectasia patient. PLoS Med. doi: 10.1371/journal.pmed.1000029 3. Bauer G, Elsallab M, Abou-El-Enein M (2018) Concise Review: A Comprehensive Analysis of Reported Adverse Events in Patients Receiving Unproven Stem Cell-Based Interventions. Stem Cells Transl. Med. doi: 10.1002/sctm.17-0282 4. Berkowitz AL, Miller MB, Mir SA, Cagney D, Chavakula V, Guleria I, et al. (2016) Glioproliferative lesion of the spinal cord as a complication of stem-cell tourism. N. Engl. J. Med. doi: 10.1056/NEJMc1600188 5. Hurst RW, Peter Bosch E, Morris JM, 5. Dyck PJB, Reeves RK (2013) Inflammatory hypertrophic cauda equina following intrathecal neural stem cell injection. Muscle and Nerve. doi: 10.1002/mus.23920 6. Julian K, Yuhasz N, Hollingsworth E, Imitola J (2018) The Growing Reality of the Neurological Complications of Global Stem Cell Tourism. Semin Neurol. doi: 10.1055/s-0038-1649338 7. Kuriyan AE, Albini TA, Townsend JH, Rodriguez M, Pandya HK, Leonard RE, et al. (2017) Vision loss after intravitreal injection of autologous “stem Cells” for AMD. N Engl J Med. doi: 10.1056/NEJMoa1609583 8. Lee BS, Achey RL, Yeaney GA, Bosler DS, Aly Z, Ontaneda D, et al. (2018) Stem cell injection180 induced glioneuronal lesion of the cauda equina. Neurology. doi: 10.1212/WNL.0000000000005219

2/14/2020 Thanks and Disclosures UCSF Neurology Outpatient Conference Thanks! John Engstrom, M.D. Neuropathology-Dr. Emily Sloan, Dr. Marta Margeta February 14, 2020 Neurosurgery-Dr. Line Jacques Neurology-Dr. Felicia Chow, Dr. Arnold Just Another Lumbar Polyradiculopathy? Kriegstein, Dr. Michael Wilson Disclosures I have no conflicts of interest to disclose 1 2 Hx: Other Symptoms Hx: LBP + Bilateral Leg Pain 12/17 • 61 yo man with LBP and bilateral (R > L) leg • Bilat calf weakness + decr bulk onset 7/17 pain, weakness, numbness since 4/17 – Decreased ability to push off with his feet • Pain worse with sitting, best supine – True calf cramps • Tingling below knees beginning 8/17 • No nocturnal pain, head or spine trauma, MVA or whiplash, IVDU, steroid use • No falls, but reduced balance with occasional tripping over right or left foot • No hx cancer, or chronic infection of lungs, skin, urinary tract or teeth • Using Meloxicam and Lyrica for pain with minimal benefit • No fever, chills , sweats 3 4 1