Melanoma represents the third most common cause of CNS metastases. Immunotherapy has evolved as a treatment option for patients with stage-IV melanoma. Stereotactic radiosurgery (SRS) also elicits an immune response within the brain and may interact with immunotherapy. We report a cohort of patients treated for brain metastasis with immunotherapy and evaluate the effect of SRS timing on the intracranial response. Methods: All consecutively treated melanoma patients receiving Ipilimumab and SRS for their brain metastasis were included in the retrospective analysis. 46 patients harboring 232 brain metastases were reviewed. The median clinical follow-up was 7.9 months (3-42.6). Median age was 63 years (24.3-83.6). 32 patients received SRS before or during ipilimumab cycles (Group-A) whereas 14 patients received SRS after the ipilimumab treatment (Group-B). Radiographic and clinical responses were assessed at approximately 3 months intervals after SRS. Results: The two cohorts were comparable in pertinent pre-treatment aspects with the exception of SRS timing relative to ipilimumab. Local recurrence free duration (LRFD) was significantly longer in Group-A patients (19.6 months, range 1.1-34.7 months) as compared to group-B patients (3 months, range 0.4-20.4 months), respectively (p=0.002). Post-SRS perilesional edema was more significant in Group-A. Conclusions: The effect of SRS and ipilimumab in attaining LRFD seems greater when SRS is performed before or during ipilimumab treatments. The timing of immunotherapy and SRS may effect LRFD and post-radiosurgical edema. The interactions between immunotherapy and SRS warrant further investigation so as to optimize the therapeutic benefits and mitigate the risks associated with multimodality, targeted therapy.

Background: It remains difficult to predict which patients will experience ongoing seizures or neuropsychological deficits following Temporal Lobe Epilepsy (TLE) surgery. MRI allows measurement of brain structures, such as the contralateral (non-resected) hippocampus (cHC) after TLE surgery. Preliminary evidence suggests that the cHC atrophies following surgery, however, the time course of this atrophy, relation to cognitive deficits and seizure outcome remains unclear. Methods: T1-weighted MR imaging and hippocampal volumetry in 26 TLE patients pre- and post-TLE surgery (and 12 controls) as: 1) two-scan group (TSG) (pre- and post-operatively at 5.4 years) and 2) longitudinal group (LG; pre- and on post-operatively on day 1,2,3,6,60,120 and at an average 2.4 years. Seizure outcome and pre- and post-operative neuropsychological assessment was performed. Results: The TSG had significant atrophy by 12% of the unresected cHC (p<0.0001) most pronounced (27%) in the hippocampal body alone. The LG revealed that this atrophy occured rapidly over the first week (1.3%/day; 3%/day cHC body). Significantly greater cHC atrophy was observed in those with ongoing seizures versus the seizure free (p=0.048). Conclusions: Significant cHC atrophy following TLE surgery that begins immediately, progresses over the first week, and remains signficantly depressed. The severity postoperative cHC atrophy may represent an early biomarker of the propensity for delayed seizure recurrence.

Background: Previous reports suggest that although a diagnostic muscle biopsy can confirm the presence of Pompe disease, the absence of a definitive biopsy result does not rule out the diagnosis. Methods: In this study, we reviewed patients with a limb-girdle syndrome who demonstrated nonspecific abnormalities of muscle, without evidence of the classical changes of acid maltase deficiency. These patients were rescreened for Pompe disease using dried blood spot (DBS) testing. Results: Twenty-seven patients provided blood samples for the DBS test. Four patients underwent subsequent genetic testing. Genetic analysis demonstrated that one patient tested positive for Pompe disease and one patient had one copy of a pathogenic variant. Conclusions: In conclusion, the ability of a diagnostic muscle biopsy to definitively rule out the presence of Pompe disease is limited. There is a role for a screening DBS in all patients presenting with a limb-girdle syndrome without a clear diagnosis.

Background: Several studies have compared early-onset Parkinson disease (EOPD) and late-onset Parkinson disease (LOPD) but most are not based on autopsy confirmed cases. Methods: We compared clinical and pharmacological profiles, time to reach irreversible Hoehn and Yahr (H&Y) Stage 3 and levodopa motor complications in autopsy confirmed EOPD and LOPD cases. Results: At first clinic visit EOPD cases were younger but had longer disease duration and they died at a younger age (all p<0.0001). Anti-Parkinsonian drug use, including levodopa, was significantly delayed in EOPD. Lifetime use of amantadine (p<0.05) and dopamine agonists (p<0.01) were higher in EOPD. While lifetime use of levodopa was similar in the two groups, levodopa was used for a significantly longer period by EOPD (p< 0.0001). EOPD had a higher cumulative incidence of dyskinesias (p<0.01), wearing-off (p<0.01), and on-off (p<0.01). However, the time to dyskinesia onset was similar in the two groups. The threshold to wearing-off was much longer in EOPD (p<0.01). H&Y stage profile at first visit was similar in the two groups. The duration from disease onset to reach irreversible H&Y stage 3 was significantly longer in EOPD. Conclusions: Our observations indicate that progression of PD is slower in EOPD and suggest that the pre-clinical interval in this group is longer. These findings can be used for case selection for drug trials and studies of the pathogenesis of PD.

Background: Pedunculopontine nucleus (PPN) has complex reciprocal connections with basal ganglia, especially with internal globus pallidus and substantia nigra, and it has been postulated that PPN stimulation may improve gait instability and freezing of gait. In this meta-analysis, we will assess the evidence for PPN deep brain stimulation in treatment of gait and motor abnormalities especially focusing on Parkinson disease patients. Methods: PubMed and Scopus electronic databases were searched for related studies published before February 2014. Medline (1966-2014), Embase (1974-2010), CINAHL, Web of Science, Scopus bibliographic, and Google Scholar databases (1960-2014) were also searched for studies investigating effect of PPN deep brain stimulation in treatment of postural and postural instability and total of ten studies met the inclusion criteria for this analysis. Results: Our findings showed a significant improvement in postural instability (p<0.001) and motor symptoms of Parkinson disease on and off medications (p<0.05), but failed to show improvement in freezing of gait. Conclusions: Despite significant improvement in postural instability observed in included studies, evidence from current literature is not sufficient to generalize these findings to the majority of patients.

Background: Electrical stimulation (ES) to promote corticospinal tract (CST) repair has been recently examined, though remains under investigated. We examine the role of motor cortex ES on axonal re-growth and functional recovery in a spinal cord injury (SCI) rat model. Methods: A partial transection was performed at C4 in 48 rats. Animal groups included: ES333 rats (n=14; 333Hz, biphasic pulse, 0.2ms every 500ms), ES20 (n=14; 20Hz, biphasic pulse, 0.2ms every 1ms), SCI only (n=10), and sham (n=10; electrode insertion without ES). Rats were trained in stairwell-grasping with subsequent SCI and ES. Post-injury reaching scores were recorded weekly, and histology completed quantifying axonal re-growth. Results: Post-SCI grasping (p<0.01, ANOVA) and well reached were lower than baseline values (p<0.01, ANOVA) for all groups. ES20 animals had lower grasping scores (p=0.03, ANOVA) and farthest well reached scores post-SCI than controls (p=0.03, ANOVA). ES333 rats had more axonal collaterals (axonal sprouts rostral to lesion) compared to control animals (p<0.01, M-W). No difference was found between groups with respect to axonal regeneration into the lesion (p=0.13, ANOVA). Conclusions: Cortical ES of the injured CST results in greater axonal outgrowth, and influences functional outcomes depending on ES parameters. ES is a potentially promising SCI therapy, but further investigation is required.

Transitional cell carcinoma (TCC) of the renal pelvis is a rare urological malignancy, with only a handful of cases of metastases to the brain reported in literature. We aim to present a case of intracranial metastasis in a female patient with history of renal pelvic carcinoma, and review existing literature of brain metastases from renal pelvic TCC. Methods: We searched PubMed, EMBASE, and MEDLINE from 1966 to January 2016 for published case reports written in English. Results: Five published case reports describe intracranial metastases from renal pelvic TCC. Our case is a 56-year-old woman with known high grade renal pelvic carcinoma and pulmonary metastases, who presented nine years after her initial diagnosis with mild left side weakness and headaches. She was found to have two lesions in the right cerebral hemisphere and underwent surgical resection of the larger right frontal lobe mass. Her neurologic symptoms improved postoperatively. She declined whole brain radiotherapy and remains stable at 6 months’ follow-up. This is the first published case of presentation of brain metastases from pelvic TCC more than 12 months after diagnosis of the primary cancer. Conclusion: There is minimal literature of renal pelvic TCC metastasizing to the brain. However, as systemic chemotherapy leads to improved survival from the primary cancer, it is possible for more cases to appear, necessitating increased awareness from the healthcare team.

Background: Patients with Rett syndrome (RTT) may demonstrate parkinsonian features. Here, we report a preliminary cross-sectional and prospective evaluation of the evolution, regional distribution, and eventual incidence of rigid tone in a cohort of MECP2 mutation-positive patients. Methods: In 51 participants, muscle tone rigidity in extremity regions and neck plus hypomimia were quantified using an RTT rigidity distribution (RTTRD) score with a range of 0 to 15. RTTRD scores were correlated with age, ability to walk and speak, mutation type, and, in a small subgroup (n=9), cerebrospinal fluid (CSF) homovanillic acid (HVA) and 5-hydroxyindole-acetic acid levels. Results: Participant ages ranged from 2 years and 5 months, to 54 years. Rigidity was found in 43/51 (84.3%); it appeared as early as age 3, increased in extent with age, and was present in all participants aged ≥13. Ankle region rigidity appeared first, followed by proximal legs, arms, neck, and face. Ambulatory participants (n=21) had lower RTTRD scores than nonambulatory (n=30; p=0.003). We found a trend to lower scores in participants with retained speech (n=13) versus those with none (n=38; p=0.074), and no difference in scores for those with truncating (n=25) versus missense mutations (n=22; p=0.387). RTTRD scores correlated negatively with CSF HVA levels (R=−0.83; p=0.005), but not with 5-hydroxyindole-acetic acid levels (R=−0.45; p=0.22). Conclusions: Although assessment of muscle tone is somewhat subjective and the RTTRD has not been validated, this study nevertheless suggests that parkinsonian rigidity in RTT is common and frequently increases in extent with age; its severity correlates directly with impaired ambulation and inversely with CSF HVA levels.

Background: Glioblastoma multiforme (GBM) is known to have poor prognosis, with no available imaging marker that can predict survival at the time of diagnosis. Diffusion weighted images are used in characterisation of cellularity and necrosis of GBM. The purpose of this study was to assess whether pattern or degree of diffusion restriction could help in the prognostication of patients with GBM. Material and Methods: We retrospectively analyzed 84 consecutive patients with confirmed GBM on biopsy or resection. The study was approved by the institutional ethics committee. The total volume of the tumor and total volume of tumor showing restricted diffusion were calculated. The lowest Apparent Diffusion Coefficient (ADC) in the region of the tumor and in the contralateral Normal Appearing White Matter were calculated in order to calculate the nADC. Treatment and follow-up data in these patients were recorded. Multivariate analsysis was completed to determine significant correlations between different variables and the survival of these patients. Results: Patient survival was significantly related to the age of the patient (p<0.0001; 95% CI-1.022-1.043) and the nADC value (p=0.014; 95% CI-0.269-0.860) in the tumor. The correlation coefficients of age and nADC with survival were −0.335 (p=0.002) and 0.390 (p<0.001), respectively. Kaplan Meier survival function, grouped by normalized Apparent Diffusion Coefficient cut off value of 0.75, was significant (p=0.007). Conclusion: The survival of patients with GBM had small, but significant, correlations with the patient’s age and nADC within the tumor.

Russian-born, Vienna-trained neurologist and neuropathologist Ilya Mark Scheinker collaborated with Josef Gerstmann and Ernst Sträussler in 1936 to describe the familial prion disorder now known as Gerstmann-Sträussler-Scheinker disease. Because of Nazi persecution following the annexation of Austria by Nazi Germany, Scheinker fled from Vienna to Paris, then after the German invasion of France, to New York. With the help of neurologist Tracy Putnam, Scheinker ended up at the University of Cincinnati, although his position was never guaranteed. He more than doubled his prior publications in America, and authored three landmark neuropathology textbooks. Despite his publications, he was denied tenure and had difficulty professionally in the Midwest because of prejudice against his European mannerisms. He moved back to New York for personal reasons in 1952, dying prematurely just 2 years later. Scheinker was twice uprooted, but persevered and eventually found some success as a refugee.