INVITED REVIEW Neurophysiology of Complex Spinal Cord Untethering Francesco Sala,* Vincenzo Tramontano,† Giovanna Squintani,† Chiara Arcaro,* Ema Tot,* Giampietro Pinna,*‡ and Mario Meglio* Summary: Surgery of complex spinal dysraphisms can be challenging. A number of surgical maneuvers can place the conus and the cauda equina at risk for neurological injury during cord untethering, and the identification of functional neural structures within the lumbosacral region is often not possible solely on the basis of anatomy. Therefore, the assistance of intraoperative neurophysiological monitoring can be invaluable during these procedures. We describe the intraoperative neurophysiological monitoring strategy developed at our institution over the past 12 years when dealing with tethered cord surgery. Monitoring and mapping techniques are described, with a focus on the invaluable role played by neurophysiological mapping. This latter, for a neurosurgeon, impacts tethered cord surgery at least as strongly as neurophysiological monitoring. Our results suggest that the combination of monitoring and mapping techniques increases the safety of these procedures, minimizing long-term morbidity and improving the degree of cord untethering. Key Words: tethered cord surgery, conus lipoma, neurophysiological mon- itoring, neurophysiological mapping. (J Clin Neurophysiol 2014;31: 326–336) A tethered cord can be generally described as any pathologic fixation of the spinal cord in an abnormal caudal location. Secondary neurulation starts about day 26 postconceptional age. The caudal neural tube and notochord remnants blend into the caudal cell mass that will originate genitourinary, notochordal, and neural structures. Within this mass, vacuoles form, coalesce, and fuse with the central canal of the spinal cord. Then a sort of apoptotic phenomenon with retrogressive differentiation occurs, and most of the distal cord, except for the conus, involutes into a glial–ependymal strand: the filum terminale. During secondary neurulation, the spine elongates faster than the spinal cord with progressive ascension of the conus. When the conus attains adult level in the spine is still a matter of debate. Some authors suggest that the cord ascends between 30th and 40th weeks of gestational age (S ¸ ahin et al., 1997; Wolf et al., 1992). Others provide some evidence that the cord is still ascending at birth and reaches the adult level within the first few months of life (Barson, 1969; Wilson and Prince, 1989). Tethering of the spinal cord can be secondary to a number of spinal dysraphisms or be primarily characterized by a lower lying conus medullaris (generally lower than the L2-L3 disc level), a thickened filum (Yundt et al., 1997) or a fatty filum (McLendon et al., 1988), without other associated pathologies. Some patients, adults and children, present symptoms of a tethered cord even in the presence of a normal level conus medullaris (Warder and Oakes, 1993, 1994). This may be explained by the fact that their filum terminale has lost most of his elasticity (George et al., 2003; Selçuki et al., 2003). Hoffman et al. first described the tethered cord syndrome (TCS) in 1976. They described 31 children with spina bifida occulta presenting with low back pain, progressive neurological deficits involving lower limbs, urologic disturbances (mainly incontinence), and orthopedic abnormalities (Hoffman et al., 1976). This clinical entity is typically recognized in patients with previous repair of open myelomeningocele at birth or in patients with occult spinal dysraphism, such as lipoma of the filum, lipomyelo- meningocele, diastematomyelia, dermal sinus tracts, and others. In reality, some of these “occult” dysraphisms have cutaneous markers, such as hypertrichosis, capillary hemangioma, a dermal sinus tract, subcutaneous lipoma, or simply an asymmetrical gluteal cleft. The pathophysiology of the tethered cord syndrome was first described by Yamada in 1981 (Yamada et al., 1981). He described a marked metabolic and electrophysiological susceptibility to hyp- oxic stress of the lumbosacral cord under constant or intermittent traction. This ultimately results in an impairment of oxidative metab- olism within the conus. Experimentally, untethering the cord improved mitochondrial oxidative metabolism. What determines when symptoms begin is likely how much tension there is on the filum terminale. Some patients present with progressive symptoms since childhood, others have a stable neuro- logical deficit, foot deformity, or scoliosis recognized in childhood but with new or progressive symptomatology in adulthood. A few patients present with symptoms only when they reach adulthood. An indirect confirmation that the natural history of a tethered cord is usually a progressive loss of neurological function over years is the fact that older patients rarely present neurologically intact. However, some patients may remain asymptomatic through life, and it is difficult to define the incidence of truly asymptomatic tethered cords in the adult population because most of these patients will never undergo an MRI study. Pain, motor weakness, and bladder dysfunction are the most common symptoms also in the adult population but pain is more frequent than in children. Although the debate on the surgical indications for asymptomatic patients is still ongoing (Kulkarni et al., 2004; Pang et al., 2010), there is more agreement on the treatment of symptomatic patients. These should be operated on, and the sooner the better, to increase the chance of reversing a neu- rological deficit. In adults, the rate of improvement with surgery ranges between 86% for pain and 35% to 71% for sensorimotor disturbances. Bladder-bowel dysfunctions are reversible in only 16% to 60% of the cases, and this is one reason not to delay un- tethering once the diagnosis of TCS is made (Hertzler et al., 2010). Surgery for cord untethering is not trivial. In large series of surgeries for spinal cord untethering, the incidence of permanent From the *Section of Neurosurgery, Department of Neurological and Movement Sciences, University of Verona, Verona, Italy; and Divisions of †Neurology and ‡Neurosurgery Department of Neurosciences, University Hospital, Verona, Italy. Address correspondence and reprint requests to Francesco Sala, MD, Section of Neurosurgery, Department of Neurological and Movement Sciences, Univer- sity of Verona, University Hospital, Piazzale Stefani 1, Verona 37124, Italy; e-mail: francesco.sala@univr.it. Copyright Ó 2014 by the American Clinical Neurophysiology Society ISSN: 0736-0258/14/3104-0326 326 Journal of Clinical Neurophysiology  Volume 31, Number 4, August 2014