Trigeminal Neuralgia as a Primary Demyelinating Disease: Potential Multimodal Evidence and Remaining Controversies.

Trigeminal neuralgia is a heterogeneous disorder with likely multifactorial and complex etiology; however, trigeminal nerve demyelination and injury are observed in almost all patients with trigeminal neuralgia. The current management strategies for trigeminal neuralgia primarily involve anticonvulsants and surgical interventions, neither of which directly address demyelination, the pathological hallmark of trigeminal neuralgia, and treatments targeting demyelination are not available. Demyelination of the trigeminal nerve has been historically considered a secondary effect of vascular compression, and as a result, trigeminal neuralgia is not recognized nor treated as a primary demyelinating disorder. In this article, we review the evolution of our understanding of trigeminal neuralgia and provide evidence to propose its potential categorization, at least in some cases, as a primary demyelinating disease by discussing its course and similarities to multiple sclerosis, the most prevalent central nervous system demyelinating disorder. This proposed categorization may provide a basis in investigating novel treatment modalities beyond the current medical and surgical interventions, emphasizing the need for further research into demyelination of the trigeminal sensory pathway in trigeminal neuralgia. PERSPECTIVE: This article proposes trigeminal neuralgia as a demyelinating disease, supported by histological, clinical, and radiological evidence. Such categorization offers a plausible explanation for controversies surrounding trigeminal neuralgia. This perspective holds potential for future research and developing therapeutics targeting demyelination in the condition.

Protective Effect of Vitamin D Supplementation on Some Hemogram Derived Inflammatory Indices in Normal and High-Fat Diet Fed Male Wistar Rats.

Background: Hematological inflammatory indices are currently suggested to assess systemic inflammation. This study aims to investigate a vitamin D supplementation effect on hematological indices of inflammation in rats. Method: Forty-eight middle-aged male rats were allocated into a normal diet (ND) group (10% fat) and a high-fat diet (HFD) group (60% fat). The animals were fed for 26 weeks. After this period, each group was randomly divided into three subgroups, each of 8 rats: Group (1): animals were fed the ND and HFD containing 1 IU/g vitamin D for 4 months, group (2): animals were fed the ND and HFD containing 6 IU/g vitamin D for 4 months and group (3): animals were euthanized to evaluate the HFD effect. Serum 25-hydroxyvitamin D level, white blood cell count (WBCs), platelet count, platelet crit (PCT), mean platelet volume (MPV), platelet distribution width (PDW), platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR) were measured. Results: The HFD, significantly increased body weight, PCT, PDW, PLR, NLR, and MLR and significantly reduced serum vitamin D levels compared to the ND (P < 0.05). There was a significant decrease in food intake, MPV, PDW, and NLR after vitamin D supplementation in the ND-fed group (P < 0.05). A significant reduction in platelet count, PCT, and MLR was observed after vitamin D supplementation in HFD-fed rats (P < 0.05). Conclusions: In our study, some hemogram-derived inflammatory indices were higher in the HFD-fed group, and vitamin D supplementation lowering effects on some hematological indices were seen in both ND and HFD groups.

Trigeminal neuralgia in multiple sclerosis: Association with demyelination and progression.

BACKGROUND: Trigeminal neuralgia (TN) is a well-recognized symptom of multiple sclerosis (MS), yet its clinical characteristics related to MS subtype is poorly studied. Our aim was to evaluate whether development and clinical outcome of TN are influenced by MS phenotype. METHODS: In this retrospective cohort study, our database from 2007 to 2022 was reviewed to identify patients who had both the diagnosis of MS and TN, whether TN was an initial symptom of MS or developed later in diagnosis. A detailed medical history and treatment outcome was obtained. Pain status was assessed retrospectively using the Barrow Neurological Institute Pain Scale (BNI-PS), with BNI-PS I-III considered as good pain control and BNI-PS IV-V as poor pain control. RESULTS: 58 patients had MS-related TN. 44 patients had relapsing remitting multiple sclerosis (RRMS) at the time of TN diagnosis, 11 had secondary progressive multiple sclerosis (SPMS) at the time of TN diagnosis, and type of MS was not clear in 3 patients at the time of TN diagnosis (either RRMS or SPMS). Over a mean follow up of 18.8 (SD=10.9) years, 30 transitioned to SPMS. TN was refractory to medical management in 9 RRMS and 22 SPMS patients (p = 0.001). TN patients with RRMS required lower median number of pain medications compared to SPMS (p = 0.014). Brain MRI was available in 41 of the entire cohort. Of these, 27 patients had demyelinating lesions in the trigeminal sensory pathway and 14 did not. Patients with existing lesions had a higher chance of failure of medical management (74% versus 36%, p = 0.017) and required surgical intervention (55% versus 7%, p = 0.003). DISCUSSION: TN was not seen in primary progressive multiple sclerosis (PPMS). In patients who transitioned to SPMS, TN was more likely to be refractory to medical management. TN was more refractory in the presence of demyelinating plaque involving trigeminal sensory pathway.

The Long-Term Outcome of Radiofrequency Ablation in Multiple Sclerosis-Related Symptomatic Trigeminal Neuralgia.

BACKGROUND: Radiofrequency lesioning (RFL) is used to surgically manage trigeminal neuralgia (TN) secondary to multiple sclerosis (MS). However, the long-term outcome of RFL has not been established. OBJECTIVE: To investigate the long-term clinical outcome of RFL in MS-related TN (symptomatic trigeminal neuralgia [STN]). METHODS: During a 23-yr period, institutional data were available for 51 patients with STN who underwent at least one RFL procedure to treat facial pain. Patient outcome was evaluated at a mean follow-up of 69 mo (95% confidence interval; range 52-86 mo). No pain with no medication (NPNM) was the primary long-term outcome measure. RESULTS: After an initial RFL procedure, immediate pain relief was achieved in 50 patients (98%), and NPNM as assessed at 1, 3, and 6 yr was 86%, 52%, and 22%, respectively. At the last clinical visit after an initial RFL, 23 patients (45%) with pain recurrence underwent repeat RFL; NPNM at 1, 3, and 6 yr after a repeat RFL was 85%, 58%, and 32%, respectively. There was no difference in pain outcome after an initial and repeat RFL ( P = .77). Ten patients with pain recurrence underwent additional RFL procedures. Two patients developed mastication muscle weakness, one patient experienced a corneal abrasion, which resolved with early ophthalmological interventions, and one patient experienced bothersome numbness. CONCLUSION: RFL achieves NPNM status in STN and can be repeated with similar efficacy.

Applications of Umbilical Cord Derived Mesenchymal Stem Cells in Autoimmune and Immunological Disorders: From Literature to Clinical Practice.

Mesenchymal Stem Cells (MSCs) enable a novel approach to stem cell therapy. Bone Marrow (BM) was the first source used in MSCs therapy. However, BM has a number of key limitations as a source of MSCs, such as the existence of only a small number of MSCs in the tissue; the painful, ethically problematic, and invasive nature of the associated collection process; and a decrease in MSC specifications as the age of donors increases. As a result, there has been increasing scholarly attention towards identifying alternative sources for MSCs. In specific, Umbilical Cord Mesenchymal Stem Cells (UC-MSCs) have been identified as a valuable source from which MSC may be obtained with potentially fewer ethical issues. MSCs can regulate the immune response, promote tissue repair, increase regeneration, and improve anticancer effects. Thus, they are significant allogenic and autologous representatives for curing malignant and non-malignant disorders. In this review, therefore, the prospective applications for curing autoimmune disorders will be considered.

Deciphering the Role of Glutamate Signaling in Glioblastoma Multiforme: Current Therapeutic Modalities and Future Directions.

As the most popular intrinsic neoplasm throughout the brain, glioblastoma multiforme (GBM) is resistant to existing therapies. Due to its invasive nature, GBM shows a poor prognosis despite aggressive surgery and chemoradiation. Therefore, identifying and understanding the critical molecules of GBM can help develop new therapeutic strategies. Glutamatergic signaling dysfunction has been well documented in neurodegenerative diseases as well as in GBM. Inhibition of glutamate receptor activation or extracellular glutamate release by specific antagonists inhibits cell development, invasion, and migration and contributes to apoptosis and autophagy in GBM cells. This review outlines the current knowledge of glutamate signaling involvement and current therapeutic modalities for the treatment of GBM.

Comparison of prognostic indices in patients who undergo melanoma brain metastasis radiosurgery.

OBJECTIVE The goal of this study was to use 4 prognostic indices to compare survival times of patients who underwent Gamma Knife stereotactic radiosurgery (SRS) to treat melanoma brain metastases. METHODS The authors analyzed 422 consecutive patients (1440 brain metastases) who underwent Gamma Knife SRS. The median total brain tumor volume was 4.7 cm3 (range 0.3-69.3 cm3), and the median number of metastases was 2 (range 1-32). One hundred thirty-two patients underwent whole-brain radiation therapy. Survival times were compared using recursive partitioning analysis (RPA), the Score Index for Radiosurgery (SIR), the Basic Score for Brain Metastases (BSBM), and the Diagnosis-Specific Graded Prognostic Assessment (DS-GPA). RESULTS The overall survival times after SRS were compared. With the RPA index, survival times were 2.6 months (Class III, n = 27), 5.5 months (Class II, n = 348), and 13.0 months (Class I, n = 47). With the DS-GPA index, survival times were 2.8 months (Scores 0-1, n = 67), 4.2 months (Scores 1.5-2.0, n = 143), 6.6 months (Scores 2.5-3.0, n = 111), and 9.4 months (Scores 3.5-4.0, n = 101). With the SIR, survival times were 3.2 months (Scores 0-3, n = 56), 5.8 months (Scores 4-7, n = 319), and 12.7 months (Scores 8-10, n = 47). With the BSBM index, survival times were 2.6 months (BSBM0, n = 47), 5.4 months (BSBM1, n = 282), 11.0 months (BSBM2, n = 86), and 8.8 months (BSBM3, n = 7). The DS-GPA index was the most balanced by case numbers in each class and provided the overall best prognostic index for overall survival. CONCLUSIONS The DS-GPA index proved most balanced and predictive of survival for patients with melanoma who underwent SRS as part of management for brain metastases. Patients whose DS-GPA score was ≥ 2.5 had predictably improved survival times after SRS.

A proposed plan for personalized radiosurgery in patients with trigeminal neuralgia.

OBJECTIVE During the last 25 years, more than 100,000 patients worldwide with trigeminal neuralgia (TN) have undergone stereotactic radiosurgery (SRS) with a standard dose of radiation. However, the radiobiological effect of radiation is determined by the amount of energy delivered to the tissue (integral dose [ID] = mean dose × target volume) and is directly associated with the nerve volume. Although the trigeminal nerve volume varies among patients with TN, the clinical impact of this variation in delivered energy is unknown. The objective of this study was to evaluate the effect of delivered ID on the outcome of TN radiosurgery. METHODS The authors evaluated 155 patients with unilateral TN who had undergone SRS as their initial surgical management over a 13-year period. The authors measured the postganglionic ID within the SRS target and retrospectively stratified patients into 3 groups: low (< 1.4 mJ), medium (1.4-2.7 mJ), and high (> 2.7 mJ) ID. Clinical outcomes, which included pain status (scored using the Barrow Neurological Institute Pain Scale) and sensory dysfunction (scored using the Barrow Neurological Institute Numbness Scale), were evaluated at a median follow-up of 71 months. RESULTS Patients who were treated with a medium ID had superior pain relief either with or without medications (p = 0.006). In the medium ID group, the rates of complete pain relief without medications at 1, 3, and 6 years after SRS were 67%, 54%, and 33%, respectively, while the rates in the rest of the cohort were 55%, 36%, and 19%, respectively. Patients given a high ID had a higher rate of post-SRS trigeminal sensory deterioration (p < 0.0001). At 1, 3, and 6 years after SRS, the high ID group had an estimated rate for developing sensory dysfunction of 35%, 45%, and 50%, respectively, while the rates in patients receiving low and medium IDs were 3%, 4%, and 9%, respectively. The optimal clinical outcome (maximum pain relief and minimal trigeminal sensory dysfunction) was obtained in patients who had received a medium ID. CONCLUSIONS With current dose selection methods, nerve volume affects long-term clinical outcomes in patients with TN who have undergone SRS. This study suggests that the prescribed SRS dose should be customized for each TN patient based on the nerve volume.

Connecting Neuronal Cell Protective Pathways and Drug Combinations in a Huntington's Disease Model through the Application of Quantitative Systems Pharmacology.

Quantitative Systems Pharmacology (QSP) is a drug discovery approach that integrates computational and experimental methods in an iterative way to gain a comprehensive, unbiased understanding of disease processes to inform effective therapeutic strategies. We report the implementation of QSP to Huntington's Disease, with the application of a chemogenomics platform to identify strategies to protect neuronal cells from mutant huntingtin induced death. Using the STHdh Q111 cell model, we investigated the protective effects of small molecule probes having diverse canonical modes-of-action to infer pathways of neuronal cell protection connected to drug mechanism. Several mechanistically diverse protective probes were identified, most of which showed less than 50% efficacy. Specific combinations of these probes were synergistic in enhancing efficacy. Computational analysis of these probes revealed a convergence of pathways indicating activation of PKA. Analysis of phospho-PKA levels showed lower cytoplasmic levels in STHdh Q111 cells compared to wild type STHdh Q7 cells, and these levels were increased by several of the protective compounds. Pharmacological inhibition of PKA activity reduced protection supporting the hypothesis that protection may be working, in part, through activation of the PKA network. The systems-level studies described here can be broadly applied to any discovery strategy involving small molecule modulation of disease phenotype.

Stereotactic Radiosurgery as Initial Surgical Management for Elderly Patients with Trigeminal Neuralgia.

BACKGROUND: Management of older patients with medically refractory trigeminal neuralgia (TN) is yet a matter of debate. OBJECTIVE: We sought to determine the benefit of stereotactic radiosurgery (SRS) as the sole surgical management in older patients (≥70 years). METHODS: One hundred and twenty-seven patients (≥70 years) with typical TN underwent SRS as initial surgical management. The median maximum dose for the first procedure was 80 Gy. Repeat SRS was performed in 46 patients who developed recurrent pain. RESULTS: After the first SRS, the initial pain control was achieved in 91% of patients. Complete pain relief (Barrow Neurological Institute [BNI] score I) developed in 75 patients (59%) and was maintained in 59, 39, and 22% of patients at 1, 3, and 5 years. Following repeat SRS, the rate of complete pain relief was 79, 55, and 41% at 1, 3, and 5 years. The chance of BNI I preservation was greater after repeat SRS compared to initial SRS (hazards ratio: 2.02, p < 0.0001). The incidence of trigeminal sensory loss was 17% after initial SRS but increased to 39% after repeat SRS. CONCLUSIONS: SRS alone was used effectively in older TN patients to achieve pain control. Recurrent pain responded to retreatment but was associated with an increased risk of sensory dysfunction.

The clinical significance of persistent trigeminal nerve contrast enhancement in patients who undergo repeat radiosurgery.

OBJECTIVE Contrast enhancement of the retrogasserian trigeminal nerve on MRI scans frequently develops after radiosurgical ablation for the management of medically refractory trigeminal neuralgia (TN). The authors sought to evaluate the clinical significance of this imaging finding in patients who underwent a second radiosurgical procedure for recurrent TN. METHODS During a 22-year period, 360 patients underwent Gamma Knife stereotactic radiosurgery (SRS) as their first surgical procedure for TN at the authors' center. The authors retrospectively analyzed the data from 59 patients (mean age 72 years, range 33-89 years) who underwent repeat SRS for recurrent pain at a median of 30 months (range 6-146 months) after the first SRS. The isocenter was 4 mm, and the median maximum doses for the first and second procedures were 80 Gy and 70 Gy, respectively. A neuroradiologist and a neurosurgeon blinded to the treated side evaluated the presence of nerve contrast enhancement on MRI series at the time of the repeat procedure. The authors correlated the presence of this imaging change with clinical outcomes. Pain outcomes and development of trigeminal sensory dysfunction were evaluated with the Barrow Neurological Institute (BNI) Pain Scale and BNI Numbness Scale, respectively. The mean length of follow-up after the second SRS was 58 months (95% CI 49-68 months). RESULTS At the time of the repeat SRS, contrast enhancement of the trigeminal nerve on MRI scans was observed in 31 patients (53%). Five years after the SRS, patients with this enhancement had lower actuarial rates of complete pain relief after the repeat SRS (27% [95% CI 7%-47%]) than patients without the enhancement (76% [95% CI 58%-94%]) (p < 0.001). At the 5-year follow-up, patients with the contrast enhancement also had a higher risk for trigeminal sensory loss after repeat SRS (75% [95% CI 59%-91%]) than patients without contrast enhancement (26% [95% CI 10%-42%]) (p = 0.001). Dysesthetic pain after repeat SRS was observed for 8 patients with and for 2 patients without contrast enhancement. CONCLUSIONS Trigeminal nerve contrast enhancement on MRI scans observed at the time of a repeat SRS for TN was associated with less satisfactory pain control and more frequently detected facial sensory loss. Residual contrast enhancement at the time of a repeat SRS may warrant consideration of dose reduction or further separation of the radiosurgical targets.

Stereotactic radiosurgery for recurrent vestibular schwannoma after previous resection.

OBJECTIVE The goal of this retrospective cohort study was to assess long-term outcomes in patients with vestibular schwannoma (VS) who underwent stereotactic radiosurgery (SRS) after initial microsurgical resection. METHODS From the authors' database of 1770 patients with VS, the authors retrospectively analyzed data from 173 Gamma Knife SRS procedures for VS after 1 (128 procedures) or multiple (45 procedures) microsurgical resections. The median length of the interval between the last resection and SRS was 42 months (range 2-329 months). The median length of clinical follow-up was 74 months (range 6-285 months). Progression-free survival after SRS was determined with Kaplan-Meier analysis. RESULTS At the time of SRS, the hearing of 161 patients (93%) was Gardner-Robertson Class V, and 81 patients (47%) had facial neuropathy (i.e., facial function with House-Brackmann [HB] grades of III-VI), 87 (50%) had trigeminal neuropathy, and 71 (41%) reported imbalance or disequilibrium disorders. The median tumor volume was 2.7 cm3 (range 0.2-21.6 cm3), and the median dose to the tumor margin was 13 Gy (range 11-20 Gy). Radiosurgery controlled growth of 163 (94%) tumors. Progression-free survival after SRS was 97% at 3 years, 95% at 5 years, and 90% at 10 years. Four patients with delayed tumor progression underwent repeat SRS at a median of 35 months (range 23-64 months) after the first SRS. Four patients (2.3%) with tumor progression underwent repeat resection at a median of 25 months (range 19-33 months). Among the patients with any facial dysfunction (indicated by HB grades of II-VI), 19% had improvement in this condition after SRS, and 5.5% with some facial function (indicated by HB grades of I-V) developed more facial weakness. Among patients with trigeminal neuropathy, 20% had improvement in this condition, and 5.8% developed or had worsened trigeminal neuropathy after SRS. CONCLUSIONS Stereotactic radiosurgery offered a safe and effective long-term management strategy for VS patients whose tumors remained or recurred after initial microsurgery.

Stereotactic radiosurgery for intracranial hemangiopericytomas: a multicenter study.

OBJECTIVE Hemangiopericytomas (HPCs) are rare tumors widely recognized for their aggressive clinical behavior, high recurrence rates, and distant and extracranial metastases even after a gross-total resection. The authors report a large multicenter study, through the International Gamma Knife Research Foundation (IGKRF), reviewing management and outcome following stereotactic radiosurgery (SRS) for recurrent or newly discovered HPCs. METHODS Eight centers participating in the IGKRF participated in this study. A total of 90 patients harboring 133 tumors were identified. Patients were included if they had a histologically diagnosed HPC managed with SRS during the period 1988-2014 and had a minimum of 6 months' clinical and radiological follow-up. A de-identified database was created. The patients' median age was 48.5 years (range 13-80 years). Prior treatments included embolization (n = 8), chemotherapy (n = 2), and fractionated radiotherapy (n = 34). The median tumor volume at the time of SRS was 4.9 cm3 (range 0.2-42.4 cm3). WHO Grade II (typical) HPCs formed 78.9% of the cohort (n = 71). The median margin and maximum doses delivered were 15 Gy (range 2.8-24 Gy) and 32 Gy (range 8-51 Gy), respectively. The median clinical and radiographic follow-up periods were 59 months (range 6-190 months) and 59 months (range 6-183 months), respectively. Prognostic variables associated with local tumor control and post-SRS survival were evaluated using Cox univariate and multivariate analysis. Actuarial survival after SRS was analyzed using the Kaplan-Meier method. RESULTS Imaging studies performed at last follow-up demonstrated local tumor control in 55% of tumors and 62.2% of patients. New remote intracranial tumors were found in 27.8% of patients, and 24.4% of patients developed extracranial metastases. Adverse radiation effects were noted in 6.7% of patients. During the study period, 32.2% of the patients (n = 29) died. The actuarial overall survival was 91.5%, 82.1%, 73.9%, 56.7%, and 53.7% at 2, 4, 6, 8, and 10 years, respectively, after initial SRS. Local progression-free survival (PFS) was 81.7%, 66.3%, 54.5%, 37.2%, and 25.5% at 2, 4, 6, 8, and 10 years, respectively, after initial SRS. In our cohort, 32 patients underwent 48 repeat SRS procedures for 76 lesions. Review of these 76 treated tumors showed that 17 presented as an in-field recurrence and 59 were defined as an out-of-field recurrence. Margin dose greater than 16 Gy (p = 0.037) and tumor grade (p = 0.006) were shown to influence PFS. The development of extracranial metastases was shown to influence overall survival (p = 0.029) in terms of PFS; repeat (multiple) SRS showed additional benefit. CONCLUSIONS SRS provides a reasonable rate of local tumor control and a low risk of adverse effects. It also leads to neurological stability or improvement in the majority of patients. Long-term close clinical and imaging follow-up is necessary due to the high probability of local recurrence and distant metastases. Repeat SRS is often effective for treating new or recurrent HPCs.

A refractory arachnoid cyst presenting with tremor, expressive dysphasia, and cognitive decline.

BACKGROUND: Arachnoid cysts are common incidental findings on intracranial imaging, although they are rarely symptomatic. CASE DESCRIPTION: We present a case of a 49 year-old woman with a recurrent left supraorbital arachnoid cyst who developed staring spells, expressive dysphasia, and tremor after cyst fenestration and cystoperitoneal shunting. Her symptoms resolved after removing the shunt valve and creating a valveless system. The case is discussed and the literature reviewed. CONCLUSION: We present a case of a recurrent arachnoid cyst that developed worsening and new symptoms after cysto-peritoneal shunting with a programmable valve, which reducing the pressure in the cyst resulted in remarkable resolution of her symptoms.

Early Radiosurgery Improves Hearing Preservation in Vestibular Schwannoma Patients With Normal Hearing at the Time of Diagnosis.

PURPOSE: Vestibular schwannomas (VS) are increasingly diagnosed in patients with normal hearing because of advances in magnetic resonance imaging. We sought to evaluate whether stereotactic radiosurgery (SRS) performed earlier after diagnosis improved long-term hearing preservation in this population. METHODS AND MATERIALS: We queried our quality assessment registry and found the records of 1134 acoustic neuroma patients who underwent SRS during a 15-year period (1997-2011). We identified 88 patients who had VS but normal hearing with no subjective hearing loss at the time of diagnosis. All patients were Gardner-Robertson (GR) class I at the time of SRS. Fifty-seven patients underwent early (≤2 years from diagnosis) SRS and 31 patients underwent late (>2 years after diagnosis) SRS. At a median follow-up time of 75 months, we evaluated patient outcomes. RESULTS: Tumor control rates (decreased or stable in size) were similar in the early (95%) and late (90%) treatment groups (P=.73). Patients in the early treatment group retained serviceable (GR class I/II) hearing and normal (GR class I) hearing longer than did patients in the late treatment group (serviceable hearing, P=.006; normal hearing, P<.0001, respectively). At 5 years after SRS, an estimated 88% of the early treatment group retained serviceable hearing and 77% retained normal hearing, compared with 55% with serviceable hearing and 33% with normal hearing in the late treatment group. CONCLUSIONS: SRS within 2 years after diagnosis of VS in normal hearing patients resulted in improved retention of all hearing measures compared with later SRS.

Hearing subclassification may predict long-term auditory outcomes after radiosurgery for vestibular schwannoma patients with good hearing.

OBJECTIVE In the era of MRI, vestibular schwannomas are often recognized when patients still have excellent hearing. Besides success in tumor control rate, hearing preservation is a main goal in any procedure for management of this population. The authors evaluated whether modified auditory subclassification prior to radiosurgery could predict long-term hearing outcome in this population. METHODS The authors reviewed a quality assessment registry that included the records of 1134 vestibular schwannoma patients who had undergone stereotactic radiosurgery during a 15-year period (1997-2011). The authors identified 166 patients who had Gardner-Robertson Class I hearing prior to stereotactic radiosurgery. Fifty-three patients were classified as having Class I-A (no subjective hearing loss) and 113 patients as Class I-B (subjective hearing loss). Class I-B patients were further stratified into Class I-B1 (pure tone average ≤ 10 dB in comparison with the contralateral ear; 56 patients), and I-B2 (> 10 dB compared with the normal ear; 57 patients). At a median follow-up of 65 months, the authors evaluated patients' hearing outcomes and tumor control. RESULTS The median pure tone average elevations after stereotactic radiosurgery were 5 dB, 13.5 dB, and 28 dB in Classes I-A, I-B1, and I-B2, respectively. The median declines in speech discrimination scores after stereotactic radiosurgery were 0% for Class I-A (p = 0.33), 8% for Class I-B1 (p < 0.0001), and 40% for Class I-B2 (p < 0.0001). Serviceable hearing preservation rates were 98%, 73%, and 33% for Classes I-A, I-B1, and I-B2, respectively. Gardner-Robertson Class I hearing was preserved in 87%, 43%, and 5% of patients in Classes I-A, I-B1, and I-B2, respectively. CONCLUSIONS Long-term hearing preservation was significantly better if radiosurgery was performed prior to subjective hearing loss. In patients with subjective hearing loss, the difference in pure tone average between the affected ear and the unaffected ear was an important factor in long-term hearing preservation.

Concomitant depression and anxiety negatively affect pain outcomes in surgically managed young patients with trigeminal neuralgia: Long-term clinical outcome.

BACKGROUND: Onset of trigeminal neuralgia (TN) is uncommon in young adults with less favorable benefit from surgical interventions. The aim of this study was to evaluate the role of concomitant psychosomatic disorders in long-term surgical outcomes in this population. METHODS: Twenty-one patients younger than 30 years of age were diagnosed initially as having medically refractory TN, and each patient underwent microvascular decompression (MVD) as initial surgical management. Correlation of clinical outcome and psychosomatic disorders (DSM-IV) was evaluated during a 15-year interval. RESULTS: A total of 93 procedures were performed for the management of TN and subsequent iatrogenic craniofacial pain disorders. At a median of 81 months, 8 of 21 patients were free of facial pain. Fourteen patients with concomitant major depressive disorder (MDD) or other anxiety disorders underwent a higher median of procedures compared with 7 patients without known MDD or anxiety (4.5 versus 1 intervention, P = 0.038). Two of 14 patients who were diagnosed with MDD or other anxiety disorders were free of craniofacial pain, whereas 6 of 7 patients without mood or anxiety disorders were free of craniofacial pain (P = 0.0005). Thirteen patients developed treatment-related complications that required further surgical procedures. Presence of MDD or other anxiety disorders was associated with higher rate of complications (P = 0.026). One patient with past medical history of severe anxiety died of unknown causes. CONCLUSIONS: In young patients with TN, comorbid MDD or anxiety disorders was associated with seeking multiple invasive procedures in multiple academic centers with limited benefit and high rates of surgical induced complications.

Early radiosurgery provides superior pain relief for trigeminal neuralgia patients.

OBJECTIVE: We evaluated factors associated with better outcomes after stereotactic radiosurgery (SRS) when it was performed as the first surgical procedure for medically refractory trigeminal neuralgia. METHODS: A total of 121 patients (median age 72 years) with medically refractory pain and no prior surgery underwent Gamma Knife SRS as their initial surgical procedure for trigeminal neuralgia. Using a single 4-mm isocenter, patients received an average maximum dose of 80 Gy, delivered to the trigeminal nerve target defined by intraoperative MRI. The median follow-up was 36 months. RESULTS: Pain relief (Barrow Neurological Institute [BNI] score I-IIIa) was achieved in 107 (88%) patients at a median time of 1 month. Patients who underwent earlier SRS (within 3 years of pain onset) had a shorter interval until pain relief (1 week, p < 0.001), had a longer interval of pain relief off medication (BNI-I, p < 0.001), and had a longer duration of adequate pain control (BNI-I-IIIa, p < 0.001). Median pain-free intervals for patients who underwent SRS at 1, 2, 3, and more than 3 years after trigeminal neuralgia diagnosis were 68, 37, 36, and 10 months, respectively. Patients who responded to SRS within the first 3 weeks after SRS had a longer duration of complete pain relief compared to those with longer response times (p = 0.001). Fifteen patients (12%) reported new sensory dysfunction after SRS. CONCLUSION: Early SRS as the initial surgical procedure for management of refractory trigeminal neuralgia was associated with faster, better, and longer pain relief when compared to late SRS. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that in patients with medically refractory trigeminal neuralgia, early stereotactic radiosurgery as the initial procedure provides faster, better, and longer pain relief.

Hearing preservation up to 3 years after gamma knife radiosurgery for Gardner-Robertson class I patients with vestibular Schwannomas.

BACKGROUND: Vestibular schwannoma patients with Gardner-Robertson (GR) class I hearing seek to maintain high-level hearing whenever possible. OBJECTIVE: To evaluate hearing outcomes at 2 to 3 years in GR class I patients who underwent Gamma Knife radiosurgery (GKRS). METHODS: Sixty-eight patients with GR class I hearing were identified between 2006 and 2009. Twenty-five patients had no subjective hearing loss (group A) and 43 patients reported subjective hearing loss (group B) before GKRS. The median tumor volume (1 cm) and tumor margin dose (12.5 Gy) were the same in both groups. RESULTS: Serviceable hearing retention rates (GR grade I or II) were 100% for group A compared with 81% at 1 year, 60% at 2 years, and 57% at 3 years after GKRS for group B patients. Group A patients had significantly higher rates of hearing preservation in either GR class I (P < .001) or GR class II (P < .001). Patients with a pure tone average (PTA) <15 dB before GKRS had significantly higher rates of preservation of GR class I or II hearing. CONCLUSION: At 2 to 3 years after GKRS, patients without subjective hearing loss or a PTA <15 dB had higher rates of grade I or II hearing preservation. Modification of the GR hearing classification into 2 groups of grade I hearing (group A, those with no subjective hearing loss and a PTA <15 dB; and group B, those with subjective hearing loss and a PTA >15 dB) may be useful to help predict hearing preservation rates at 2 to 3 years after GKRS.

Gamma Knife radiosurgery of olfactory groove meningiomas provides a method to preserve subjective olfactory function.

Anosmia is a common outcome after resection of olfactory groove meningioma(s) (OGM) and for some patients represents a significant disability. To evaluate long term tumor control rates and preservation of subjective olfaction after Gamma Knife (GK) stereotactic radiosurgery (SRS) of OGM. We performed a retrospective chart review and telephone assessments of 41 patients who underwent GK SRS between 1987 and 2008. Clinical outcomes were stratified by full, partial or no subjective olfaction, whereas tumor control was assessed by changes in volume greater or lesser than 25%. The median clinical and imaging follow-up were 76 and 65 months, respectively. Prior to SRS, 19 (46%) patients had surgical resections and two (5%) had received fractionated radiation therapy. Twenty four patients (59%) reported a normal sense of smell, 12 (29%) reported a reduced sense of smell and five (12%) had complete anosmia. The median tumor volume was 8.5 cm(3) (range 0.6-56.1), the mean radiation dose at the tumor margin was 13 Gy (range 10-20) and the median estimated dose to the olfactory nerve was 5.1 Gy (range 1.1-18.1). At follow-up, 27 patients (66%) reported intact olfaction (three (7%) described return to a normal sense of smell), nine (22%) described partial anosmia, and five (12%) had complete anosmia. No patient reported deterioration in olfaction after SRS. Thirteen patients (32%) showed significant tumor regression, 26 (63%) had no further growth and two (5%) had progressed. The progression free tumor control rates were 97% at 1 year and 95% at 2, 10 and 20 years. Symptomatic adverse radiation effects occurred in three (7%) patients. Stereotactic radiosurgery provided both long term tumor control and preservation of olfaction.