Deep brain stimulation in dystonia: State of art and future directions.

When considering Deep Brain Stimulation (DBS) surgical treatment of dystonia syndromes, it is important to consider multiple aspects of the disease and its presentation. It is crucial to know if the dystonia is idiopathic, inherited or acquired as well as focal, segmental or generalised. Careful phenotyping of idiopathic as well as inherited dystonias and accurate diagnosis of acquired dystonias informs the decision-making process for patients and clinicians by providing them with useful predictors of outcomes of the proposed surgery. Here, we provided a review of the current literature, highlighted the areas where evidence is scarce and suggested future directions for research.

Rapid memory T-cell reconstitution recapitulating CD45RA-depleted haploidentical transplant graft content in patients with hematologic malignancies.

T-cell depletion of an HLA-haploidentical graft is often used to prevent GVHD, but the procedure may lead to increased graft failure, relapse and infections due to delayed immune recovery. We hypothesized that selective depletion of the CD45RA+ subset can effectively reduce GVHD through removal of naive T cells, while providing improved donor immune reconstitution through adoptive transfer of CD45RA- memory T cells. Herein, we present results from the first 17 patients with poor-prognosis hematologic malignancy, who received haploidentical donor transplantation with CD45RA-depleted progenitor cell grafts following a novel reduced intensity conditioning regimen without TBI or serotherapy. Extensive depletion of CD45RA+ T cells and B cells, with preservation of abundant memory T cells, was consistently achieved in all 17 products. Neutrophil engraftment (median day +10) and full donor chimerism (median day +11) was rapidly achieved post transplantation. Early T-cell reconstitution directly correlated with the CD45RA-depleted graft content. T-cell function recovered rapidly with broad TCR Vß spectra. There was no infection-related mortality in this heavily pretreated population, and no patient developed acute GVHD despite infusion of a median of >100 million per kilogram haploidentical T cells.

Chimeric antigen receptor-redirected CD45RA-negative T cells have potent antileukemia and pathogen memory response without graft-versus-host activity.

Chimeric antigen receptor (CAR)-redirected cellular therapy is an attractive modality for cancer treatment. We hypothesized that allogeneic CAR-engineered CD45RA-negative T cells can control cancer and infection without the risk of graft-versus-host disease (GVHD). We used CD19(+) MLL-rearranged leukemia as prototype because it is an aggressive and generally drug-resistant malignancy. CD45RA(-) cells that were transduced with anti-CD19 CAR containing 4-1BB and CD3ζ signaling domains effectively lysed MLL-rearranged leukemia cell lines and primary blasts in vitro. In a disseminated leukemia mouse model, CAR(+)CD45RA(-) cells significantly reduced leukemia burdens and prolonged overall survival without GVHD. CAR(+) cells were sustainable in blood, and all the treated mice remained leukemia-free even after they were re-challenged with leukemia cells. Despite the transduction process, CD45RA(-) cells retained recall activity both in vitro and in vivo against human pathogens commonly found in cancer patients. In comparison with CD45RA(+) cells, CD45RA(-) cells showed less allogeneic activity in mixed leukocyte reactions and in mouse models. Thus, the use of CAR(+)CD45RA(-) cells can separate GVHD from graft-versus-malignancy effect and infection control. These cells should also be useful in nontransplant settings and may be administered as off-the-shelf third-party cells.

Two cases of unexpected long-term improvement of Parkinson's disease after subthalamic nucleus deep brain stimulation removal.

Two patients with Parkinson's disease (PD) treated successfully with subthalamic nucleus deep brain stimulation (STN-DBS) for 3-4 years are reported, who demonstrated a persistent improvement following removal of STN-DBS for late infection. Possible hypotheses are discussed--whether a microlesioning effect or a disease-modifying effect of STN-DBS, though neither adequately explain this phenomenon.

Cerebral haemorrhage from a remote varix in the venous outflow of an arteriovenous malformation treated successfully by embolisation.

We describe a case of intracerebral haemorrhage in the temporal lobe arising from a distal varix related to the venous outflow of an ipsilateral frontal arteriovenous malformation (AVM). AVM itself and associated arterial aneurysms are well-known risk factors for haemorrhage. In this patient, haemorrhage had occurred from a distal varix. This is the first reported case of successful endovascular embolisation of a frontal AVM with spontaneous regression of an associated remote varix. [corrected].

Risk factors for early post-operative psychiatric symptoms in patients undergoing epilepsy surgery for temporal lobe epilepsy.

OBJECTIVE: De-novo psychiatric symptoms may develop within 3 months after a temporal lobectomy for epilepsy. The objective of this study was to identify presurgical risk factors for psychiatric symptoms. METHODS: Twenty-seven patients who had a temporal lobectomy for epilepsy were included. Twenty-four had hippocampal sclerosis or gliosis, and three had cavernous haemagiomata. Twelve had operations on the left, and 15 on the right side. Twenty-four patients were rendered free of seizures (SZ) with loss of awareness, three had early post-operative convulsions, one continued to have habitual SZ. RESULTS: Nine patients (33%) developed low mood, anxiety and emotional lability within 3 months after surgery. Patients with early post-operative psychiatric symptoms were younger (27.9/34.8 years, P = 0.01), and more anxious on the presurgical Hospital Anxiety and Depression Scale (12/8.44, P = 0.02) than patients without post-operative psychiatric symptoms. There was also an association between right temporal lobectomies and early post-surgical symptoms (P = 0.02 Fisher's exact test). CONCLUSION: Potential risk factors were age, anxiety and operation on the right side. Larger studies are required to determine if these risk factors are independent.

Predictors of outcome after temporal lobectomy for refractory temporal lobe epilepsy.

OBJECTIVE: To identify predictors of outcome after epilepsy surgery in patients with temporal lobe epilepsy (TLE). METHODS: Seventy-six patients with normal magnetic resonance imaging (MRI) or hippocampal sclerosis on MRI who underwent anterior temporal lobe resections were included. Outcome 2 years after surgery was classified as good (Engel I and II) or poor (Engel III and IV). Gender, age at onset and duration of epilepsy, history of febrile convulsions, auras, right- or left-sided TLE, memory ipsilateral to seizure onset (Wada test), hippocampal asymmetry (HA) and T2 relaxation time, amygdala, temporal lobe and hemispheral volume were tested for associations with outcome. RESULTS: Sixty-seven percent had a good outcome. Of all parameters tested, only a history of febrile convulsions and HA on quantitative MRI were significantly associated with a good seizure outcome. The absence of these parameters did not exclude a good outcome, but only five of 18 patients (28%) without HA and without a history of febrile convulsions had a good outcome. CONCLUSION: Febrile convulsions and HA were predictors of outcome after epilepsy surgery in TLE. Subtle volume loss in amygdala, temporal lobe or hemispheres and the memory ipsilateral to the side of resection were not associated with outcome.

Primary Nocardia farcinica brain abscess with secondary meningitis and ventriculitis in an immunocompetent patient, successfully treated with moxifloxacin.

We report a rare case of Nocardia farcinica occipital brain abscess in an immunocompetent patient with no underlying risk factors successfully treated with the antibiotic moxifloxacin. The patient underwent craniotomy and abscess drainage. Initial post-operative treatment with co-trimoxazole produced a limited response. Despite the development of skull base meningitis and ventriculitis subsequent addition of moxifloxacin produced an excellent outcome.

The seizure outcome after amygdalohippocampectomy and temporal lobectomy.

The aim of this study was to compare the seizure outcome of two different types of epilepsy surgery, selective amygdalohippocampectomy (AHE) and anterior temporal lobectomy (ATLE) in patients with temporal lobe epilepsy. We included 114 patients who had mesio-temporal lobe epilepsy and hippocampal sclerosis or gliosis on histology. Patients had ATLE if the non-dominant hemisphere was affected or if the whole temporal lobe was atrophic. Patients had AHE if the dominant hemisphere was affected. Standardized seizure outcome at 1 year following surgery was used. Overall 40% of the 114 patients who had temporal lobe epilepsy surgery were seizure-free at 1-year (Engel's class Ia). A good outcome (Engel's classes I and II) was significantly more frequent in ATLE than in AHE. (66% and 44%, respectively, P = 0.03). ATLE had a better seizure outcome than AHE.

Autologous transplantation of CD133 selected hematopoietic progenitor cells for treatment of relapsed acute lymphoblastic leukemia.

A 21-year-old white male with relapsed acute lymphoblastic leukemia (ALL) developed an invasive Zygomycosis infection 3 weeks after beginning re-induction chemotherapy. Because of the high risk of fatal recurrence of the fungal infection, neither long-term maintenance chemotherapy nor allogeneic hematopoietic stem cell transplant (HSCT) was considered appropriate. Because his ALL blasts expressed CD34 but lacked CD133, he received a CD133 selected autologous graft following high-dose consolidation chemotherapy. The patient survives in remission 19 months after HSCT.

Use of the NeuroMate stereotactic robot in a frameless mode for functional neurosurgery.

BACKGROUND: The aim of this paper is to describe the use of the NeuroMate stereotactic robot for functional neurosurgery with a novel frameless ultrasound registration system. METHODS: A retrospective review of the evaluation and clinical use of the NeuroMate stereotactic robot in a frameless mode for functional neurosurgery. RESULTS: Prior to its clinical use a phantom study was undertaken to demonstrate an application accuracy of 1.29 mm. Subsequently the robot has been used in 153 functional neurosurgical procedures including 113 deep brain stimulator implantations. CONCLUSIONS: The NeuroMate stereotactic robot in a frameless mode has sufficient accuracy for a range of functional neurosurgical procedures, including movement disorder surgery.

Quantification of tumour response to radiotherapy.

In 1979, the World Health Organization (WHO) established criteria based on tumour volume change for classifying response to therapy as (i) progressive disease (PD), (ii) partial recovery (PR), and (iii) no change (NC). Typically, the tumour volume is reported from diameter measurements, using the calliper method. Alternatively, the Cavalieri method provides unbiased volume estimates of any structure without assumptions about its shape. In this study, we applied the Cavalieri method in combination with point counting to investigate the changes in tumour volume in four patients with high grade glioma, using 3D MRI. In particular, the volume of tumour within the enhancement boundary, the enhancing abnormality (EA), was estimated from T(1) weighted images, and the volume of the non-enhancing abnormality, (NEA) enhancing abnormality, was estimated from T(2) relaxation time and magnetic transfer ratio tissue characterization maps. We compared changes in tumour volume estimated by the Cavalieri method with those obtained using the calliper method. Absolute tumour volume differed significantly between the two methods. Analysis of relative change in tumour volume, based on the WHO criteria, provided a different classification using the calliper and Cavalieri methods. The benefit of the Cavalieri method over the calliper method in the estimation of tumour volume is justified by the following factors. First, Cavalieri volume estimates are mathematically unbiased. Second, the Cavalieri method is highly efficient under an appropriate sampling density (i.e. EA volume estimates can be obtained with a coefficient of error no higher than 5% in 2-3 min). Third, the source of variation of the volume estimates due to disagreements between observers, and within observer, is much greater in the positioning of the calliper diameters than in the identification of the tumour boundaries when applying the Cavalieri method. Additionally, the error prediction formula, available to estimate the coefficient of error of Cavalieri volume estimates from the data, allows us to establish more precise classification criteria against which to identify potentially clinical significant changes in tumour volume.

Artifactually low glycated haemoglobin in a patient with severe hypertriglyceridaemia.

This report describes a case of artifactually low glycated haemoglobin (Hb) in a patient with type II diabetes and severe hypertriglyceridaemia. The effect of hypertriglyceridaemia on glycated Hb determination using the Abbott Vision method was investigated in a series of patients with diabetes. The interference of triglycerides in glycated Hb assays was also investigated by two other methods, the Beckman Synchron CX4 delta immunoturbidimetric method, and the Primus affinity chromatography high performance liquid chromatography assay.

Fish odour syndrome with features of both primary and secondary trimethylaminuria.

We report a patient with the fish odour syndrome who has both primary and secondary trimethylaminuria. The diagnosis was made using biochemical and genetic analysis in the apparent absence of any characteristic smell. Differentiation of primary and secondary trimethylaminuria is usually made on urinary analysis of trimethylamine and its metabolite trimethylamine N-oxide, with different, characteristic patterns of both compounds in primary and secondary trimethylaminuria. Our patient had biochemical analysis consistent with a diagnosis of secondary trimethylaminuria, while analysis of the flavin-containing mono-oxygenase 3 gene, the causative gene in primary trimethylaminuria, demonstrated three sequence polymorphisms, two of which are known to reduce enzyme activity. The patient showed temporary clinical and biochemical response to treatment with metronidazole and neomycin. It is important to be aware of this diagnosis in patients without obvious clinical signs, and of the subjective benefits of treatment.