Somatotopic organization of the human spinothalamic tract: in vivo computed tomography-guided mapping in awake patients undergoing cordotomy.

OBJECTIVEThe location of the human spinothalamic tract (STT) in the anterolateral spinal cord has been known for more than a century. The exact nature of the neuronal fiber lamination within the STT, however, remains controversial. After correlating in vivo macrostimulation-induced pain/temperature sensation during percutaneous cervical cordotomy with simultaneous CT imaging of the electrode tip location, the authors present a modern description of the somatotopy of the human cervical STT.METHODSTwenty patients underwent CT-guided percutaneous cervical cordotomy to alleviate contralateral medication-refractory cancer pain. Patient responses to electrical stimulation (0.01-0.1 V, 50 Hz, 1 msec) were recorded and the electrode location for each response was documented with a contemporaneous CT scan. In a post hoc analysis of the data, the location for each patient's response(s) was measured and drawn on a diagram of their cord. Positive responses were represented only when the lowest possible voltage (≤ 0.02 V) elicited a response. Negative responses were recorded if there was no clinical response at 0.1 V.RESULTSClinically, patients did well with an average reduction in opiates of 75% at 1 week, and 67% were able to leave the palliative care unit. The size of the cervical cord varied between patients, with an average lateral extent (width) of 11 mm and a height of 9 mm. Responses from the lower limb were represented superficially (lateral) and posteriorly within the anterolateral cord. The area with responses from the upper limb was larger and surrounded those with responses from the lower limb primarily anteriorly and medially, but also posteriorly.CONCLUSIONSIn this study, the somatotopic organization of the human STT was elucidated for the first time using in vivo macrostimulation and contemporaneous CT imaging during cordotomy. In this cohort of patients, the STT from the lower-limb region was located superficially and posteriorly in the anterolateral quadrant of the cervical cord, with the STT from the upper-limb region surrounding it primarily anteriorly and medially (deep) but also posteriorly. The authors discuss how the previous methods of cordotomy may have biased the earlier versions of STT lamination. They suggest that an ideal spinal cord entry site for cordotomy of either the upper- or lower-limb pain fibers is halfway between the equator and anterior pole of the cord.

The effect of unilateral thalamic deep brain stimulation on the vocal dysfunction in a patient with spasmodic dysphonia: interrogating cerebellar and pallidal neural circuits.

Spasmodic dysphonia (SD) is a neurological disorder of the voice where a patient's ability to speak is compromised due to involuntary contractions of the intrinsic laryngeal muscles. Since the 1980s, SD has been treated with botulinum toxin A (BTX) injections into the throat. This therapy is limited by the delayed-onset of benefits, wearing-off effects, and repeated injections required every 3 months. In a patient with essential tremor (ET) and coincident SD, the authors set out to quantify the effects of thalamic deep brain stimulation (DBS) on vocal function while investigating the underlying motor thalamic circuitry. A 79-year-old right-handed woman with ET and coincident adductor SD was referred to our neurosurgical team. While primarily treating her limb tremor, the authors studied the effects of unilateral, thalamic DBS on vocal function using the Unified Spasmodic Dysphonia Rating Scale (USDRS) and voice-related quality of life (VRQOL). Since dystonia is increasingly being considered a multinodal network disorder, an anterior trajectory into the left thalamus was deliberately chosen such that the proximal contacts of the electrode were in the ventral oralis anterior (Voa) nucleus (pallidal outflow) and the distal contacts were in the ventral intermediate (Vim) nucleus (cerebellar outflow). In addition to assessing on/off unilateral thalamic Vim stimulation on voice, the authors experimentally assessed low-voltage unilateral Vim, Voa, or multitarget stimulation in a prospective, randomized, doubled-blinded manner. The evaluators were experienced at rating SD and were familiar with the vocal tremor of ET. A Wilcoxon signed-rank test was used to study the pre- and posttreatment effect of DBS on voice. Unilateral left thalamic Vim stimulation (DBS on) significantly improved SD vocal dysfunction compared with no stimulation (DBS off), as measured by the USDRS (p < 0.01) and VRQOL (p < 0.01). In the experimental interrogation, both low-voltage Vim (p < 0.01) and multitarget Vim + Voa (p < 0.01) stimulation were significantly superior to low-voltage Voa stimulation. For the first time, the effects of high-frequency stimulation of different neural circuits in SD have been quantified. Unexpectedly, focused Voa (pallidal outflow) stimulation was inferior to Vim (cerebellar outflow) stimulation despite the classification of SD as a dystonia. While only a single case, scattered reports exist on the positive effects of thalamic DBS on dysphonia. A Phase 1 pilot trial (DEBUSSY; clinical trial no. NCT02558634, clinicaltrials.gov) is underway at the authors' center to evaluate the safety and preliminary efficacy of DBS in SD. The authors hope that this current report stimulates neurosurgeons to investigate this new indication for DBS.

Cyclization of Motor Cortex Stimulation for Neuropathic Pain: A Prospective, Randomized, Blinded Trial.

OBJECTIVES: Programming guidelines for motor cortex stimulation (MCS) in neuropathic pain requires further investigation. After optimizing voltage as a percentage of motor threshold, we evaluated the effect of cyclizing time of stimulation on pain relief for chronic neuropathic pain. METHODS: Six patients were enrolled into this trial. In a prospective, randomized, double-blinded manner, patients were programmed to receive stimulation 100, 83.3, 66.7, or 50% of the time in 30-min intervals. Outcomes were assessed after 14 days on each setting with a visual analogue scale (VAS) for pain and the SF36 quality of life questionnaire. RESULTS: There was no significant difference (p > 0.05) between the different cyclized settings as measured by the VAS, MGPQ, or SF36 in our cohort. There were two distinct subgroups: responders (n = 4) and nonresponders (n = 2) to cyclization. Responders continued to have pain relief when stimulation was reduced to only 50% of the time (15 min ON/15 min off). Interestingly, this group subjectively preferred the 50% stimulation timing compared to 100%. Nonresponders could not tolerate cyclizing because of increased pain. CONCLUSIONS: In this small cohort, cyclization of MCS settings revealed two distinct subgroups: responders and nonresponders. Responders tolerated stimulation in all settings and 50% stimulation (15 min ON/15 min off) was their subjectively preferred setting. Cyclization in responders will prolong battery life and delay the need for INS replacement and may offer improved pain relief. Building from our previous work, we recommend clinicians consider following the Vancouver MCS programming algorithm presented in this manuscript.

Episodic hemilaryngopharyngeal spasm (HELPS) syndrome: case report of a surgically treatable novel neuropathy.

The authors describe a novel cranial neuropathy manifesting with life-threatening episodic hemilaryngopharyngeal spasm (HELPS). A 50-year-old woman presented with a 4-year history of intermittent throat contractions, escalating to life-threatening respiratory distress. Botulinum toxin injections into her right vocal cord reduced the severity of her spasms, but the episodes continued to occur. MRI demonstrated a possible neurovascular conflict involving the cranial nerve IX-X complex and the posterior inferior cerebellar artery. Microvascular decompression of the upper rootlets of the vagal nerve eliminated her HELPS without complication. The authors propose a mechanism of HELPS implicating isolated involvement of the upper motor rootlets of the vagus nerve.

A novel multi-modal platform to image molecular and elemental alterations in ischemic stroke.

Stroke is a major global health problem, with the prevalence and economic burden predicted to increase due to aging populations in western society. Following stroke, numerous biochemical alterations occur and damage can spread to nearby tissue. This zone of "at risk" tissue is termed the peri-infarct zone (PIZ). As the PIZ contains tissue not initially damaged by the stroke, it is considered by many as salvageable tissue. For this reason, much research effort has been undertaken to improve the identification of the PIZ and to elucidate the biochemical mechanisms that drive tissue damage in the PIZ in the hope of identify new therapeutic targets. Despite this effort, few therapies have evolved, attributed in part, to an incomplete understanding of the biochemical mechanisms driving tissue damage in the PIZ. Magnetic resonance imaging (MRI) has long been the gold standard to study alterations in gross brain structure, and is frequently used to study the PIZ following stroke. Unfortunately, MRI does not have sufficient spatial resolution to study individual cells within the brain, and reveals little information on the biochemical mechanisms driving tissue damage. MRI results may be complemented with histology or immuno-histochemistry to provide information at the cellular or sub-cellular level, but are limited to studying biochemical markers that can be successfully "tagged" with a stain or antigen. However, many important biochemical markers cannot be studied with traditional MRI or histology/histochemical methods. Therefore, we have developed and applied a multi-modal imaging platform to reveal elemental and molecular alterations that could not previously be imaged by other traditional methods. Our imaging platform incorporates a suite of spectroscopic imaging techniques; Fourier transform infrared imaging, Raman spectroscopic imaging, Coherent anti-stoke Raman spectroscopic imaging and X-ray fluorescence imaging. This approach does not preclude the use of traditional imaging techniques, and rather it should be use to complement traditional methods such as MRI or histology and immunohistochemistry, to gain a greater insight into disease mechanisms. We demonstrate the potential of this approach by characterizing biochemical alterations within the PIZ 24h after the induction of photothrombotic stroke in mice. Substantial molecular and elemental alterations were identified in the PIZ 24h after stroke that are consistent with tissue swelling and edema, but not oxidative stress. This reveals important mechanistic information, that could not previously be obtained, which should be considered in future studies aimed at developing therapeutic intervention from this model.

Stereotactic mesencephalotomy for palliative care pain control: A case report, literature review and plea to rediscover this operation.

Introduction Stereotactic mesencephalotomy is an ablative procedure which lesions the pain pathways (spinothalamic and trigeminothalamic tracts) at the midbrain level to treat medically refractory, nociceptive, contralateral pain. Sparsely reported in contemporary English language literature, this operation is at risk of being lost from the modern-day neurosurgical practice. Methods We present a case report and brief review of the literature on stereotactic mesencephalotomy. A 17-year-old girl with cervical cord glioblastoma and medically refractory unilateral head and neck pain was treated with contralateral stereotactic mesencephalotomy. The lesion was placed at the level of the inferior colliculus, half way between the lateral edge of the aqueduct and lateral border of the midbrain. Results The patient had no head and neck pain immediately after the procedure and remained pain-free for the remainder of her life (five months). She was weaned off her pre-operative narcotics and was able to leave hospital, meeting her palliative care goals. Conclusions Cancer-related unilateral head and neck nociceptive pain in the palliative care setting can be successfully treated with stereotactic mesencephalotomy. We believe that stereotactic mesencephalotomy is the treatment of choice for a small number of patients typified by our case. The authors make a plea to the palliative care and neurosurgical communities to rediscover this operation.

Incorporating the Spine Instability Neoplastic Score into a Treatment Strategy for Spinal Metastasis: LMNOP.

Study Design Review. Objective To describe a decision framework that incorporates key factors to be considered for optimal treatment of spinal metastasis and highlight how this system incorporates the Spinal Instability Neoplastic Score (SINS). Methods We describe how treatment options for spinal metastasis have broadened in recent years with advancements in stereotactic radiosurgery, vertebral augmentation, and other minimally invasive techniques. We discuss classification-based approaches to the treatment of spinal metastasis versus principles-based approaches and argue that the latter may be more appropriate for optimal patient informed consent. Case examples are provided. Results Scoring systems at best produce an estimate of life expectancy but fall short in incorporating all of the relevant factors that determine which treatment(s) may be indicated. We advocate a principle-based decision framework called LMNOP that considers: (L) location of disease with respect to the anterior and/or posterior columns of the spine and number of spinal levels involved (contiguous or non-contiguous); (M) mechanical instability as graded by SINS; (N) neurology (symptomatic epidural spinal cord compression); (O) oncology (histopathologic diagnosis), particularly with respect to radiosensitivity; and (P) patient fitness, patient wishes, prognosis (which is mostly dependent on tumor type), and response to prior therapy. Conclusions LMNOP is the first systematic approach to spinal metastasis that incorporates SINS. It is easy to remember, it addresses clinical factors not directly addressed by other systems, and it is adaptable to changes in technology.