Deep brain stimulation programming in Parkinson's disease: Introduction of current issues and perspectives.

Deep brain stimulation (DBS) is a well-established treatment for Parkinson's disease (PD) leading to a significant reduction in motor and non-motor symptoms. Numerous factors contribute to positive outcomes for DBS including careful patient selection, lead placement and effective programming. Only DBS programming can be modified after patient implantation, therefore DBS programming plays a crucial role in improving clinical outcomes. In this paper, we review the literature to present current issues and perspectives for DBS programming in PD. Only a few algorithms proposed by experts for the initial programming and management of some adverse effects are available. No guidelines are available for programming sessions and medical treatment management during DBS follow-up. Moreover, emergence of increasingly complex lead designs makes programming more and more complex. Fortunately, in the last few years numerous techniques have emerged for optimization of DBS programming in PD.

Heterodimer Autorepression Loop: A Robust and Flexible Pulse-Generating Genetic Module.

We investigate the dynamics of the heterodimer autorepression loop (HAL), a small genetic module in which a protein A acts as an autorepressor and binds to a second protein B to form an AB dimer. For suitable values of the rate constants, the HAL produces pulses of A alternating with pulses of B. By means of analytical and numerical calculations, we show that the duration of A pulses is extremely robust against variation of the rate constants while the duration of the B pulses can be flexibly adjusted. The HAL is thus a minimal genetic module generating robust pulses with a tunable duration, an interesting property for cellular signaling.

Targeting the red nucleus for cerebellar tremor.

Deep brain stimulation of the thalamus (and especially the ventral intermediate nucleus) does not significantly improve a drug-resistant, disabling cerebellar tremor. The dentato-rubro-olivary tract (Guillain-Mollaret triangle, including the red nucleus) is a subcortical loop that is critically involved in tremor genesis. We report the case of a 48-year-old female patient presenting with generalized cerebellar tremor caused by alcohol-related cerebellar degeneration. Resistance to pharmacological treatment and the severity of the symptoms prompted us to investigate the effects of bilateral deep brain stimulation of the red nucleus. Intra-operative microrecordings of the red nucleus revealed intense, irregular, tonic background activity but no rhythmic components that were synchronous with upper limb tremor. The postural component of the cerebellar tremor disappeared during insertion of the macro-electrodes and for a few minutes after stimulation, with no changes in the intentional (kinetic) component. Stimulation per se did not reduce postural or intentional tremor and was associated with dysautonomic symptoms (the voltage threshold for which was inversed related to the stimulation frequency). Our observations suggest that the red nucleus is (1) an important centre for the genesis of cerebellar tremor and thus (2) a possible target for drug-refractory tremor. Future research must determine how neuromodulation of the red nucleus can best be implemented in patients with cerebellar degeneration.

Severe kerion Celsi caused by Trichophyton quinckeanum: Severe kerion Celsi due to Trichophyton quinckeanum.

We report a severe case of kerion Celsi of the scalp in a previously healthy 13-year-old girl due to Trichophyton quinckeanum, an emerging dermatophyte species in Europe. The species was definitely identified by DNA sequencing and the patient was successfully treated by oral terbinafine for 6 weeks. Kerion Celsi is a severe inflammatory form of tinea capitis, which is characterised by a purulent discharge and alopecia [1]. It typically occurs in children infected with zoophilic dermatophytes, such as Trichophyton mentagrophytes, and an increasing number of cases caused by other Trichophyton species has recently been reported [2]. Herein we report a severe case of kerion Celsi of the scalp caused by the emerging species Trichophyton quinckeanum, which was successfully treated by oral antifungal.

Zygomatic implant placement using a robot-assisted flapless protocol: proof of concept.

Robotic assistance can help in physically guiding the drilling trajectory during zygomatic implant positioning. A new robot-assisted strategy for a flapless zygomatic implant placement protocol is reported here. In this protocol, a preoperative computed tomography scan is used to plan the surgical path. After surface registration, the ROSA robot (Zimmer Biomet Robotics) guides several steps, which are performed with shared control. The surgeon performs the drilling and tapping, guided by the robotic arm, which is positioned according to the planned trajectory. Placement of the zygomatic implant is done manually. Immediate intraoperative 3D verification is performed by cone beam computed tomography (flat-panel detector, Medtronic O-arm II). Four zygomatic implants were placed in the case patient according to the flapless protocol, with a mean vector error of 1.78 mm (range 0.52-4.70 mm). A screw-retained temporary prosthesis was placed on the same day. No significant complications were observed. The application of this robot-assisted surgical protocol, which guarantees a very high degree of precision, may reduce inaccuracies in the positioning of zygomatic implants that could deviate from the surgeon's plan. This appears to be a potentially safe flapless surgery technique. Drill slipping on the crest or on the maxillary wall is the main source of error in this procedure, emphasizing the usefulness of the assisted surgical guidance with haptic feedback.

Perfusion MRI as a neurosurgical tool for improved targeting in stereotactic tumor biopsies.

OBJECTIVE: Stereotactic biopsies are subject to sampling errors (essentially due to target selection). The presence of contrast enhancement is not a reliable marker of malignancy. The goal of the present study was to determine whether perfusion-weighted imaging can improve target selection in stereotactic biopsies. METHODS: We studied 21 consecutive stereotactic biopsies between June 2009 and March 2010. Perfusion-weighted magnetic resonance imaging (MRI) was integrated into our neuronavigator. Perfusion-weighted imaging was used as an adjunct to conventional MRI data for target determination. Conventional MRI alone was used to determine the trajectory. RESULTS: We found a linear correlation between regional cerebral blood volume (rCBV) and vessel density (number of vessels per mm(2); R = 0.64; p < 0.001). Perfusion-weighted imaging facilitated target determination in 11 cases (52.4%), all of which were histopathologically diagnosed as glial tumors. For glial tumors, which presented with contrast enhancement, perfusion-weighted imaging identified a more precisely delimited target in 9 cases, a different target in 1 case, and exactly the same target in 1 other case. In all cases, perfusion-selected sampling provided information on cellular features and tumor grading. rCBV was significantly associated with grading (p < 0.01), endothelial proliferation (p < 0.01), and vessel density (p < 0.01). For lesions with rCBV values ≤1, perfusion-weighted MRI did not help to determine the target but was useful for surgical management. CONCLUSIONS: For stereotactic biopsies, targeting based on perfusion-weighted imaging is a feasible method for reducing the sampling error and improving target selection in the histopathological diagnosis of tumors with high rCBVs.

Robotic implantation of deep brain stimulation leads, assisted by intra-operative, flat-panel CT.

BACKGROUND: There are two mandatory skills in deep brain stimulation (DBS) neurosurgery: accuracy and control. METHOD: Frame-based robotic registration was performed. Prior to insertion into the skull, the guide tube's position was checked with flat-panel computed tomography (fpCT). After registration against the pre-operative plan, we measured and corrected the robotic arm's position so that the guide tube with the micro-electrode would follow the planned trajectory exactly. We then used fpCT again to check the DBS lead's final position. CONCLUSION: The combination of intra-operative fpCT with robotised surgery provides an appropriate, user-friendly solution to the key technical challenges in DBS lead implantation.

Recommendations for stereotactic body radiation therapy for spine and non-spine bone metastases. A GETUG (French society of urological radiation oncolgists) consensus using a national two-round modified Delphi survey.

Background and purpose: The relevance of metastasis-directed stereotactic body radiation therapy (SBRT) remains to be demonstrated through phase III trials. Multiple SBRT procedures have been published potentially resulting in a disparity of practices. Therefore, the french society of urological radiation oncolgists (GETUG) recognized the need for joint expert consensus guidelines for metastasis-directed SBRT in order to standardize practice in trials carried out by the group. Materials and methods: After a comprehensive literature review, 97 recommendation statements were created regarding planning and delivery of spine bone (SBM) and non-spine bone metastases (NSBM) SBRT. These statements were then submitted to a national online two-round modified Delphi survey among main GETUG investigators. Consensus was achieved if a statement received ≥ 75 % agreements, a trend to consensus being defined as 65-74 % agreements. Any statement without consensus at round one was re-submitted in round two. Results: Twenty-one out of 29 (72.4%) surveyed experts responded to both rounds. Seventy-five statements achieved consensus at round one leaving 22 statements needing a revote of which 16 achieved consensus and 5 a trend to consensus. The final rate of consensus was 91/97 (93.8%). Statements with no consensus concerned patient selection (3/19), dose and fractionation (1/11), prescription and dose objectives (1/9) and organs at risk delineation (1/15). The voting resulted in the writing of step-by-step consensus guidelines. Conclusion: Consensus guidelines for SBM and NSBM SBRT were agreed upon using a validated modified Delphi approach. These guidelines will be used as per-protocole recommendations in ongoing and further GETUG clinical trials.

Analysis of somatic hypermutations of immunoglobulin gene rearrangements in childhood acute lymphoblastic leukemia.

The current study investigated the presence, frequency, and status of somatic hypermutations as well as their role in children with B lineage ALL. The obtained sequences were analyzed using IMGT/V-QUEST. Totally, 150 IGH sequences were evaluated; 139 from the 111 patients at the time of diagnosis and 11 from 8/111 patients at the time of relapse. The findings of the current report revealed the presence of somatically mutated V genes in childhood B lineage ALL. A higher frequency of somatic hypermutations was noted in unproductive rearrangements and was generally attributed to nucleotide mutation type, region, and IGHV gene subgroup biases.

T cell diversity and TcR repertoires in teleost fish.

In vertebrates, the diverse and extended range of antigenic motifs is matched to large populations of lymphocytes. The concept of immune repertoire was proposed to describe this diversity of lymphocyte receptors--IG and TR--required for the recognition specificity. Immune repertoires have become useful tools to describe lymphocyte and receptor populations during the immune system development and in pathological situations. In teleosts, the presence of conventional T cells was first proposed to explain graft rejection and optimized specific antibody production. The discovery of TR genes definitely established the reality of conventional T cells in fish. The development of genomic and EST databases recently led to the description of several key T cell markers including CD4, CD8, CD3, CD28, CTLA4, as well as important cytokines, suggesting the existence of different T helper (Th) subtypes, similar to the mammalian Th1, Th2 and Th17. Over the last decade, repertoire studies have demonstrated that both public and private responses occur in fish as they do in mammals, and in vitro specific cytotoxicity assays have been established. While such typical features of T cells are similar in both fish and mammals, the structure of particular repertoires such as the one of gut intra-epithelial lymphocytes seems to be very different. Future studies will further reveal the particular characteristics of teleost T cell repertoires and adaptive responses.

Dual, minimally invasive fixation in acute, double, thoracic spine fracture.

BACKGROUND: We report on a dual percutaneous fixation in 2 patients with a double thoracic spine fracture. The advantages and limitations of this new approach for treating traumatic spinal fractures are reviewed. CLINICAL PRESENTATION: A 67-year-old male was admitted following a fall from a height of 3 m. A neurological examination revealed sub-T11 motor and sensory paraparesis. There were a T6 vertical body and bi-articular fracture and a T11 vertebral burst fracture with > 75% posterior wall damage. A 40-year-old male was admitted after a suicide attempt. A neurological examination revealed sub-T11 paraplegia. There were a T7 vertebral body fracture with intact posterior wall and a T11 burst fracture with > 75% posterior wall damage. SURGICAL TECHNIQUE: The same technique was used in both cases. 2 minimally invasive percutaneous fixations of the 2 fractures were performed. In a third step, we performed a T10-T12 open laminectomy. This technique helped to limit blood loss and avoid an over-long fixation. Pedicle screw targeting was optimal. 16 months later, the neurological status was normal in patient 1 and there was neurological improvement in patient 2. No secondary segmental kyphotic deformities appeared.Percutaneous fixation enables the treatment of an acute thoracic spine fracture. With appropriate presurgical planning, this technique can be applied to all thoracic vertebrae. Spinal cord injuries justify the use of laminectomy together with percutaneous fixation, in order to limit erector muscle injury and blood loss.

B lymphocytes of xeroderma pigmentosum or Cockayne syndrome patients with inherited defects in nucleotide excision repair are fully capable of somatic hypermutation of immunoglobulin genes.

Recent experiments have strongly suggested that the process of somatic mutation is linked to transcription initiation. It was postulated that a mutator factor loads onto the RNA polymerase and, during elongation, causes transcriptional arrest that activates DNA repair, thus occasionally causing errors in the DNA sequence. We report the analysis of the role of one of the known DNA repair systems, nucleotide excision repair (NER), in somatic mutation. Epstein-Barrvirus-transformed B cells from patients with defects in NER (XP-B, XP-D, XP-V, and CS-A) were studied. Their heavy and light chain genes show a high frequency of point mutations in the variable (V), but not in the constant (C) regions. This suggests that these B cells can undergo somatic hypermutation despite significant defects in NER. Thus, it is doubtful that NER is an essential part of the mechanism of somatic hypermutation of Ig genes. As an aside, NER seems also not involved in Ig gene switch recombination.

A unique V-J-C-rearranged gene encodes a gamma protein expressed on the majority of CD3+ T cell receptor-alpha/beta- circulating lymphocytes.

We have recently described an mAb, anti-Ti gamma A, that recognizes an antigenic determinant carried by a TCR gamma chain. This antibody binds to approximately 3% of human PBLs and delineates a CD2+, CD3+, TCR-alpha/beta-, CD4-, CD8+/-, CD5+, NKH1-, and HLA class II- subset. The present study was designed to identify the gene encoding the Ti gamma A epitope. A first analysis was carried out on a previously characterized TCR gamma + fetal-cloned cell line termed F6C7. It was found that F6C7 cells have one gamma rearrangement on each chromosome: one joins V gamma 3 to J gamma 1, and the second joins V gamma 9 to J gamma P. Because only the latter allele appeared to be transcribed in the F6C7 lymphocytes, these data strongly suggested that anti-Ti gamma A mAb is specific for either a V gamma 9 or a V gamma 9-J gamma P-encoded peptide. To confirm this point, we studied an additional series of 13 randomly selected Ti gamma A+ cloned cells derived from peripheral blood of three distinct adult individuals. Each one of these lymphocytes was shown to both possess and transcribe a V gamma 9-J gamma P-C gamma 1-rearranged gene. It is therefore concluded that a predominant subpopulation of CD3+ TCR-alpha/beta- human circulating T lymphocytes (namely, the subset defined by anti-Ti gamma A mAb) surface expresses a gamma protein with a limited potential of variability from one cell to another.

Rearrangements of immunoglobulin and T cell receptor beta and gamma genes are associated with terminal deoxynucleotidyl transferase expression in acute myeloid leukemia.

The cell origin of the rare terminal deoxynucleotidyl transferase (TdT)-positive acute myeloid leukemias (AML) was investigated at the molecular level, by examining the configuration of the Ig H (Igh) and L (Ig kappa, Ig lambda) chain gene regions, and of the T cell receptor (TCR) beta and T cell rearranging (TRG) gamma loci. In 8 of the 10 TdT+ AML analyzed (classified as myeloid according to morphological and cytochemical criteria, and to the reactivity with one or more antimyeloid mAbs), a rearrangement of the Igh chain gene was found. In TdT- AML, evidence of an Igh gene reorganization was instead observed only in 2 of the 42 patients studied. Furthermore, evidence of TCR-beta and/or TRG-gamma gene rearrangement was observed in four AML, all of which belonged to the Igh-rearranged TdT+ group. In three cases (one TdT+ and two TdT-), the Ig kappa L chain gene was also in a rearranged position. These findings demonstrate a highly significant correlation between TdT expression and DNA rearrangements at the Igh and TCR chain gene regions and support the view that this enzyme plays an important role in the V-(D)-J recombination machinery. Overall, the genomic configuration, i.e., JH gene rearrangement sometimes coupled to a kappa L chain and TCR gene reorganization, similar to that found in non-T-ALL, suggests that in most cases of TdT+ AML, the neoplastic clone, despite the expression of myeloid-related features, is characterized by cells molecularly committed along the B cell lineage.

[Tuberculous aneurysm of abdominal aorta: case report and literature review]. / Anévrisme tuberculeux de l'aorte abdominale: cas clinique et revue de la littérature.

Tuberculous aneurysms of aorta are rare. They expose to a very high risk of unpredictable rupture with serious hemodynamic consequences. We report a 82-year-old male who presented with an tuberculous aortic aneurysm in a prerupture state. He underwent a surgical treatment and antibiotic therapy. Postoperative course was uneventful. Epidemiology, pathogenesis, presentation, management and mortality of this affection were reviewed and discussed. With appropriate medical and surgical management, the prognosis of this infection is very good.

Tension pneumocephalus and rhinorrhea revealing spontaneous cerebrospinal fluid fistula of the anterior cranial base.

Spontaneous cerebrospinal fluid fistulas (CSFFs) of the anterior skull base are extremely rare. We report a case of spontaneous CSFF of the ethmoid cribriform plate presenting with rhinorrhea and tension pneumocephalus. We discuss the physiopathology, the radiological management, and the treatment of spontaneous CSF fistulas related to the anterior skull base. A 58-year-old woman was admitted to our institution for headaches with clear rhinorrhea persisting over several days. Antecedents were unremarkable. An episode of epistaxis three days before was reported. Clinical examination showed clear rhinorrhea, headaches, and anosmia. The CT scan showed voluminous epidural and subdural pneumocephalus with mass effect on both frontal and temporal lobes. A high-resolution CT scan with bone reconstruction showed a 2-mm bony defect of the cribriform plate. Surgery consisted of epidural frontal anterior skull base repair. Postsurgery follow-up was uneventful. At one year, the patient was asymptomatic apart from the persistence of anosmia. Spontaneous CSF fistulas are uncommon and can be associated with tension pneumocephalus. The physiopathology remains unclear. Their treatment by complete exclusion of the fistula is necessary because of the lethal risk of pneumococcus meningitis.

[Follicular dural lymphoma. Case report]. / Lymphome folliculaire méningé. A propos d'un cas.

A case of a meningeal B-cell lymphoma is described. A 48-year-old man presented with an episode of grand mal seizure following a brain injury. An initial diagnosis of extradural hematoma was made based on the results of the cerebral computerized tomography scan. Magnetic resonance images demonstrated an enhanced mass with a dural tail attached to the meningeal layer of the temporal bone, suggesting a meningioma "en plaque". The mass was surgically excised. Tumoral removal was subcomplete (Simpson 2). Operative inspection also suggested a meningioma, but histological analysis and electron microscopy revealed a grade IV follicular B-cell lymphoma. Biological studies were normal. An extensive workup found an external iliac adenopathy with several osseous locations on PET. The patient underwent chemotherapy and radiotherapy. Three years after the first symptoms appeared, the patient is alive and free of symptoms. The clinicopathological features and treatments were discussed.

The human T-cell receptor gamma (TRG) genes.

The human T-cell receptor gamma (TRG) chain genes, like those encoding the T-cell receptor alpha- and beta-polypeptides, undergo rearrangements specifically in T cells. The human TRG locus, which has been completely mapped, is composed of two constant region genes (TRGC), five joining segments (TRGJ) and at least 14 variable gamma-genes (TRGV). Eight variable genes are functional and belong to four different subgroups. The product of the rearranged TRG gene is the gamma-chain which is expressed, along with the delta-chain, at the surface of a subset of T lymphocytes. Although some gamma delta + cells display a cytolytic activity, their precise function remains to be elucidated.

[Stroke due to spontaneous calcified cerebral embolus as presenting feature of calcified aortic stenosis]. / Infarctus cérébral par embolie calcaire spontanée révélant un rétrécissement aortique calcifié.

We report a case of calcified aortic stenosis revealed by an ischemic stroke. An 81-year-old man with hyperlipidemia, hypertension and renal function impairment presented with acute onset of right-sided hemiparesis and aphasia. Head CT scan revealed a rounded calcified high-density mass within the distal segment of the left anterior cerebral artery, consistent with a calcified cerebral embolus, and an infarct in the left paracentral lobule. Transesophageal echocardiography demonstrated a sclerotic aortic valve. The patient was discharged from hospital on aspirin and atorvastatin, and the outcome was favorable. Calcified embolus remains a rare event and it has been not yet reported in the territory of anterior cerebral artery. It may be observed in aortic and mitral valve diseases, calcified plaques of the internal carotid artery and aortic arch. Renal failure promotes their development and is the cause of cardiovascular diseases. To date, aortic valve calcification is not considered as a marker of stroke risk, except when associated with severe stenosis or left ventricular hypertrophy.

[Giant prebulbomedullary arachnoid cyst. Case report and review of the literature]. / Kyste arachnoïdien géant prébulbomédullaire. Cas clinique et revue de la littérature.

Usual locations of arachnoid cyst are the middle cranial fossa in 50-60%, cerebellopontine angle (10%) and suprasellar area (10%). Most of these malformations are asymptomatic. Premedullar arachnoid cysts are extremely rare. All previous cases reported were operated. We report a case of an asymptomatic giant craniocervical junction arachnoid cyst with a follow up of five years. In 2002, an adolescent consulted for persistent cervical pain. Encephalic MR showed a giant ventral craniocervical junction arachnoid cyst. Neurologic examination was normal. Conservative treatment was decided with a clinical follow up and repeated MR in case of persistent cervicalgia. Craniocervical junction arachnoid cysts are anecdotic. Medical care cannot be standardized. Pathogenesis and management are discussed.