Ekkehard M. Kasper

Deep brain stimulation of the anterior internal capsule for the treatment of Tourette syndrome: technical case report.

OBJECTIVE AND IMPORTANCE: Medical treatment of Tourette syndrome is often ineffective or is accompanied by debilitating side effects, therefore prompting the need to evaluate surgical therapies. CLINICAL PRESENTATION: We present the case of a 37-year-old woman with severe Tourette syndrome since the age of 10 years. Her symptoms included frequent vocalizations and severe head and arm jerks that resulted in unilateral blindness. Trials of more than 40 medications and other therapies had failed to relieve the tics. INTERVENTION: We implanted bilateral electrodes in the anterior limb of the internal capsule, terminating in the vicinity of the nucleus accumbens. At 18-month follow-up, optimal stimulation continued to lower her tic frequency and severity significantly. CONCLUSION: Our findings suggest that stimulation of the anterior internal capsule may be a safe and effective procedure for the treatment of Tourette syndrome.

Stereotactic Body Radiotherapy Reirradiation for Recurrent Epidural Spinal Metastases

PURPOSE When patients show progression after conventional fractionated radiation for spine metastasis, further radiation and surgery may not be options. Stereotactic body radiotherapy (SBRT) has been successfully used in treatment of the spine and may be applicable in these cases. We report the use of SBRT for 60 consecutive patients (81 lesions) who had radiological progressive spine metastasis with epidural involvement after previous radiation for spine metastasis. METHODS AND MATERIALS SBRT was used with fiducial and vertebral anatomy-based targeting. The radiation dose was prescribed based on the extent of spinal canal involvement; the dose was 8 Gy×3=24 Gy when the tumor did not touch the spinal cord and 5 to 6 Gyx5=25 to 30 Gy when the tumor abutted the cord. The cord surface received up to the prescription dose with no hot spots in the cord. RESULTS The median overall survival was 11 months, and the median progression-free survival was 9 months. Overall, 93% of patients had stable or improved disease while 7% of patients showed disease progression; 65% of patients had pain relief. There was no significant toxicity other than fatigue. CONCLUSIONS SBRT is feasible and appears to be an effective treatment modality for reirradiation after conventional palliative radiation fails for spine metastasis patients.

Melanoma brain metastasis: overview of current management and emerging targeted therapies

The high rate of brain metastasis in patients with advanced melanoma has been a clinical challenge for oncologists. Despite considerable progress made in the management of advanced melanoma over the past two decades, improvement in overall survival has been elusive. This is due to the high incidence of CNS metastases, which progress relentlessly and which are only anecdotally responsive to systemic therapies. Surgery, stereotactic radiosurgery and whole-brain radiotherapy with or without cytotoxic chemotherapy remain the mainstay of treatment. However, new drugs have been developed based on our improved understanding of the molecular signaling mechanisms responsible for host immune tolerance and for melanoma growth. In 2011, the US FDA approved two agents, one antagonizing each of these processes, for the treatment of advanced melanoma. The first is ipilimumab, an anti-CTLA-4 monoclonal antibody that enhances cellular immunity and reduces tolerance to tumor-associated antigens. The second is vemurafenib, an inhibitor that blocks the abnormal signaling for melanoma cellular growth in tumors that carry the BRAFV600E mutation. Both drugs have anecdotal clinical activity for brain metastasis and are being evaluated in clinical trial settings. Additional clinical trials of newer agents involving these pathways are also showing promise. Therefore, targeted therapies must be incorporated into the multimodality management of melanoma brain metastasis.

Health care and socioeconomic impact of falls in the elderly

BACKGROUND Elderly falls are associated with long hospital stays, major morbidity, and mortality. We sought to examine the fate of patients ≥75 years of age admitted after falls. METHODS We reviewed all fall admissions in 2008. Causes, comorbidities, injuries, procedures, mortality, readmission, and costs were analyzed. RESULTS Seven hundred eight patients ≥75 years old were admitted after a fall, with 89% being simple falls. Short-term mortality was 6%. Male sex, atrial fibrillation, acute myocardial infarction, congestive heart failure (CHF), intracranial hemorrhage, hospital-acquired pneumonia, trigger events, Clostridium difficile, and intubation were predictors of death (P < .05). Thirty-day readmission occurred in 14%; CHF, craniotomy, and acute renal failure were predictive. The median cost of hospitalization was

Extent of resection and radiotherapy in GBM: A 1973 to 2007 surveillance, epidemiology and end results analysis of 21,783 patients

11,000 with cardiac disease, anemia, major orthopedic and neurosurgical procedures, pneumonia, and intubation as predictive. CONCLUSIONS Simple falls in the elderly have high morbidity, mortality, and costs. Methodologies for prevention are warranted and should be studied intensively.

Autism gene Ube3a and seizures impair sociability by repressing VTA Cbln1

Surgery, radiation and chemotherapy are the standard of care for GBM patients, however, the impact of extent of resection (EOR) and radiotherapy (RT) on patient survival across age groups has not been established. Therefore, we present the current largest study on EOR and RT in GBM over the past three decades. Using the population based Surveillance, Epidemiology and End Results (SEER) registry, we identified a total of 21,783 GBM patients (1973-2007). Survival analysis based on EOR and RT was performed by means of factor analysis, Kaplan-Meier survival and Cox proportional hazards ratio. Age, RT and EOR were highly prognostic (p<0.00001). Combined gross total resection (GTR) and RT showed the longest median survival (11 months) compared to subtotal resection (STR) and RT (9 months). Survival times after monotherapy with RT, GTR and STR were 5, 3 and 2 months, respectively. Patients without therapy showed a median survival of 1 month. RT and GTR demonstrated highest median survival. Interestingly, survival advantage of GTR versus STR amounted to only 1-2 months. Monotherapy (GTR, STR or RT) showed a significantly lower survival rate compared to combination therapies. RT alone yielded significantly better survival compared to any resective approach. Relative to overall age-specific median survival, elderly patients still reasonably benefit from RT alone. However, across all age groups multimodality treatment with surgery and RT continues to provide the largest survival benefit compared to either treatment alone and, thus, should be pursued whenever feasible.

Phenomenology of hallucinations, illusions, and delusions as part of seizure semiology

Maternally inherited 15q11-13 chromosomal triplications cause a frequent and highly penetrant type of autism linked to increased gene dosages of UBE3A, which encodes a ubiquitin ligase with transcriptional co-regulatory functions. Here, using in vivo mouse genetics, we show that increasing UBE3A in the nucleus downregulates the glutamatergic synapse organizer Cbln1, which is needed for sociability in mice. Epileptic seizures also repress Cbln1 and are found to expose sociability impairments in mice with asymptomatic increases in UBE3A. This Ube3a–seizure synergy maps to glutamate neurons of the midbrain ventral tegmental area (VTA), where Cbln1 deletions impair sociability and weaken glutamatergic transmission. We provide preclinical evidence that viral-vector-based chemogenetic activation of, or restoration of Cbln1 in, VTA glutamatergic neurons reverses the sociability deficits induced by Ube3a and/or seizures. Our results suggest that gene and seizure interactions in VTA glutamatergic neurons impair sociability by downregulating Cbln1, a key node in the expanding protein interaction network of autism genes.

Survival after concurrent traumatic dislocation of the atlanto-occipital and atlanto-axial joints: a case report and review of the literature.

In partial epilepsy, a localized hypersynchronous neuronal discharge evolving into a partial seizure affecting a particular cortical region or cerebral subsystem can give rise to subjective symptoms, which are perceived by the affected person only, that is, ictal hallucinations, illusions, or delusions. When forming the beginning of a symptom sequence leading to impairment of consciousness and/or a classic generalized seizure, these phenomena are referred to as an epileptic aura, but they also occur in isolation. They often manifest in the fully awake state, as part of simple partial seizures, but they also can be associated to different degrees of disturbed consciousness. Initial ictal symptoms often are closely related to the physiological functions of the cortical circuit involved and, therefore, can provide localizing information. When brain regions related to sensory integration are involved, the seizure discharge can cause specific kinds of hallucinations, for example, visual, auditory, gustatory, olfactory, and cutaneous sensory sensations. In addition to these elementary sensory perceptions, quite complex hallucinations related to a partial seizure can arise, for example, perception of visual scenes or hearing music. By involving psychic and emotional spheres of human perception, many seizures also give rise to hallucinatory emotional states (e.g., fear or happiness) or even more complex hallucinations (e.g., visuospatial phenomena), illusions (e.g., déjà vu, out-of-body experience), or delusional beliefs (e.g., identity change) that often are not easily recognized as epileptic. Here we suggest a classification into elementary sensory, complex sensory, and complex integratory seizure symptoms. Epileptic hallucinations, illusions, and delusions shine interesting light on the physiology and functional anatomy of brain regions involved and their functions in the human being. This article, in which 10 cases are described, introduces the fascinating phenomenology of subjective seizure symptoms.

Augmented autologous pericranium duraplasty in 100 posterior fossa surgeries--a retrospective case series.

Study Design. A case report of a patient who survived a traumatic disassociation of both atlanto-occipital and atlantoaxial joints. Objective. To describe a rare case of concurrent atlanto-occipital and atlantoaxial dislocation with a review of the related literature regarding occipitocervical dislocation. Summary of Background Data. Cases of isolated atlanto-occipital or atlantoaxial dislocation have typically resulted in death or devastating neurologic deficit. Survival after the simultaneous dislocation at both joints is extremely rare. Methods. The initial evaluation, subsequent management, and surgical treatment of a 25-year-old male who sustained a concurrent dislocation of the atlantoaxial and atlanto-occipital joints from a motor vehicle collision are reported and the related literature is discussed. Results. The patient was transferred to our hospital after initial stabilization according to Emergency Medical Service criteria and management based on the Advanced Trauma Life Support protocol. A complete (ASIA A) spinal cord injury was diagnosed on admission. Radiographic evaluation revealed dislocations of the atlanto-occipital and atlantoaxial joints. Subsequently, the patient underwent surgical stabilization with instrumented posterior fusion from the occiput to C5. Intraoperatively, traumatic pseudomeningocele was diagnosed and repaired with pericranial autograft. The vital function parameters currently remain stable, but the patient is ventilator-dependent and did not regain motor or sensory function. Conclusion. The rapid response time of emergency medical services and stabilization according to the Advanced Trauma Life Support protocol now lead to the survival of patients with significant deficit from occipitocervical injuries. A high index of suspicion is required to appropriately manage a patient with this devastating injury in order to maximize the chance for survival.

The relation between cerebral blood flow velocities as measured by TCD and the incidence of delayed ischemic deficits. A prospective study after subarachnoid hemorrhage.

BACKGROUND: Primary closure of the dura in posterior fossa (p-fossa) surgeries is technically difficult and usually requires the use of a dural substitute. A variety of substitutes are currently available and data suggest that autologous materials are preferred in comparison with nonautologous substitutes. OBJECTIVE: To report our experience using locally harvested autologous pericranium as a dural substitute in patients who underwent p-fossa surgeries. METHODS: Retrospective analysis of patients who had undergone p-fossa craniotomies between 2005 and 2011. All patients received locally harvested autologous pericranium for duraplasty augmented with a dural sealant. Data were reviewed for complications including: surgical site infection, meningitis, cerebrospinal fluid leak, the radiographic formation of a pseudomeningocele, and any new neurological symptoms related to the incision or repair. RESULTS: One hundred patients were identified. Indications for surgery included tumor, vascular lesions, or hemorrhage requiring surgical intervention, symptomatic Chiari I malformation, microvascular decompression for trigeminal neuralgia, and trauma requiring surgical decompression. The complication rate was 1% with 1 patient developing an nonsteroidal anti-inflammatory drug-induced aseptic meningitis and graft dehiscence requiring surgical revision. CONCLUSION: Autologous pericranium with dural sealant augmentation is an effective way to repair the durotomy in p-fossa surgeries. To the best of our knowledge, this is currently the largest study using this technique in the adult neurosurgical literature. Our results report a much lower rate of complications in comparison with other duraplasty studies. ABBREVIATIONS: IV, intravenously NSAID, nonsteroidal anti-inflammatory drug p-fossa, posterior fossa