Faculty Bibliography

Although grafted cells may be promising therapy for stroke, survival of implanted neural cells in the brains of stroke patients has never been documented. Human NT2N (hNT) neurons derived from the NTera2 (NT2) teratocarcinoma cell line were shown to remain postmitotic, retain a neuronal phenotype, survive >1 year in host rodent brains and ameliorate motor and cognitive impairments in animal models of ischemic stroke. Here we report the first postmortem brain findings of a phase I clinical stroke trial patient implanted with human hNT neurons adjacent to a lacunar infarct 27 months after surgery. Neurofilament immunoreactive neurons were identified in the graft site, fluorescent in situ hybridization revealed polyploidy in groups of cells at this site just like polyploid hNT neurons in vitro, and there was no evidence of a neoplasm. These findings indicate that implanted hNT neurons survive for >2 years in the human brain without deleterious effects.

OBJECTIVE: Stereotactic radiosurgery has become an important and minimally invasive alternative for patients with refractory trigeminal neuralgia. When a second procedure is necessary, the outcomes are unknown. The degree of pain relief and morbidity after repeat radiosurgery were studied. METHODS: Thirty-one patients underwent a second gamma knife radiosurgery procedure because of unsatisfactory or unsustained relief of pain after the first procedure. Twenty-seven patients were assessable at median follow-up periods of 42.7 and 20.4 months after the first and second procedures, respectively. Most patients had undergone multiple previous operations of other types (microvascular decompression, radiofrequency rhizotomy, glycerol rhizotomy, balloon compression). The median target doses of the first and second radiosurgeries were 75 and 64 Gy, respectively. All patients were evaluated by a physician who did not participate in patient treatment. RESULTS: After the first radiosurgical procedure, 13 patients had an excellent response initially (complete relief without any medication), 3 had a good response (complete relief with some medication), 7 had a fair response (>50% relief), and 4 had a poor response (<50% pain relief or treatment failure). Repeat radiosurgery was performed in patients with recurrent or residual pain. After the second radiosurgical procedure, 5 patients had an excellent response, 8 had a good response, 10 had a fair response, and 4 had a poor response. Thirteen patients (48%) achieved complete pain relief (with or without medication). Two patients (7.4%) experienced new sensory symptoms after the first radiosurgical procedure, and three (12.7%, actuarial) experienced new sensory symptoms after the second procedure. CONCLUSION: Repeat radiosurgery provided a similar rate of pain relief as the first procedure, despite a modest dose reduction. The risk of new sensory symptoms was increased, but no other morbidity was identified. For patients who experience recurrent pain and choose to undergo a second procedure, our current procedure is to deliver a maximum dose of 50 to 60 Gy to a trigeminal target anterior to the root entry zone near the entrance of the nerve beneath the petrous dura.

Patients with acoustic neuromas have several treatment options that include observation, surgical resection, stereotactic radiosurgery, and fractionated radiotherapy. Resection is indicated for patients with larger tumors that have caused major neurologic deficits from brain compression. Surgeons perform stereotactic radiosurgery as the main alternative to acoustic tumor resection with the goals of preserved neurologic function and prevention of tumor growth. The long-term outcomes of radiosurgery, particularly with gamma knife technique, have proven its role in the primary or adjuvant management of this disease. Radiotherapy can be offered to selected patients with larger tumors in whom radiosurgery may not be feasible. Patients with neurofibromatosis type-2 pose specific challenges, particularly in regard to preservation of hearing and other cranial nerve function. The primary clinical issues include avoiding tumor-related or treatment-related mortality, prevention of further tumor-related neurologic disability, minimizing treatment risks such as spinal fluid leakage, infections, or cardiopulmonary complications, maintaining regional cranial nerve function (facial, trigeminal, cochlear, and glossopharyngeal/vagal), avoiding hydrocephalus, maintaining quality of life and employment, and reducing cost. All treatment choices should strive to meet all of these goals.

Stereotactic radiosurgery is an increasingly used and the least invasive surgical option for patients with medically refractory trigeminal neuralgia (TN). The authors began use of this technique at our center in 1992 and have evaluated outcomes serially. Independently acquired data from 220 patients with idiopathic TN that had Gamma Knife radiosurgery was reviewed. The median radiosurgery dose was 80 Gy with a range of 60 to 90 Gy. Most patients had features of typical TN, although 16 (7.3%) described additional atypical features. One hundred thirty-five patients (61.4%) had prior surgery. Patients were followed to a maximum of 6.5 years (median, 2 years). Complete or partial pain relief was achieved in 85.6% of patients at 1 year. Complete pain relief was achieved in 64.9 % of patients at 6 months, 70.3% at 1 year, and 75.4% patients at 33 months. Patients with an atypical pain component had a lower rate of achieving pain relief ( p = 0.025). Due to recurrences, 55.8% of patients had complete or partial pain relief at 5 years. The absence of preoperative sensory disturbance or prior surgery correlated with an increased proportion of patients in complete or partial pain relief over time. Ten percent of patients developed new or increased subjective facial paresthesia or facial numbness. Radiosurgery for idiopathic TN was safe and effective, and provided benefit to a patient population with a high frequency of prior surgical intervention. It is an important addition to the surgical armamentarium for TN.