Self-Mutilation in Neurodegeneration with Brain Iron Accumulation

Neurodegeneration with brain iron accumulation (NBIA) is the term applied to a heterogeneous group of disorders resulting in iron deposition in the basal ganglia. Well-known phenotypic features are progressive regression with extra pyramidal involvement and a variable course. A 10-year-old child born to consanguineous parents presented with progressive generalized opisthotonic dystonia, retrocollis, oromandibular dyskinesias, apraxia for swallowing, optic atrophy and severe self-mutilation of lips. MR imaging showed brain iron accumulation. Other causes of self-mutilation were excluded. Early infantile onset, ophisthotonic dystonia with oromandibular dyskinesias and characteristic MR images are suggestive of NBIA. There is only one case reported in the literature of self-mutilation in this condition.     

EEG in Creutzfeldt-Jakob disease.

Electroecenphalography (EEG) is an integral part of the diagnostic process in patients with Creutzfeldt-Jakob disease (CJD). The EEG has therefore been included in the World Health Organisation diagnostic classification criteria of CJD. In sporadic CJD (sCJD), the EEG exhibits characteristic changes depending on the stage of the disease, ranging from nonspecific findings such as diffuse slowing and frontal rhythmic delta activity (FIRDA) in early stages to disease-typical periodic sharp wave complexes (PSWC) in middle and late stages to areactive coma traces or even alpha coma in preterminal EEG recordings. PSWC, either lateralized (in earlier stages) or generalized, occur in about two-thirds of patients with sCJD, with a positive predictive value of 95%. PSWC occur in patients with methionine homozygosity and methionine/valine heterozygosity but only rarely in patients with valine homozygosity at codon 129 of the prion protein gene. PSWC tend to disappear during sleep and may be attenuated by sedative medication and external stimulation. Seizures are an uncommon finding, occurring in less than 15% of patients with sCJD. In patients with iatrogenic CJD, PSWC usually present with more regional EEG findings corresponding to the site of inoculation of the transmissible agent. In genetic CJD, PSWC in its typical form are uncommon, occurring in about 10%. No PSWC occur in EEG recordings of patients with variant CJD.     

Rostral anterior cingulate cortex activity in the theta band predicts response to antidepressive medication.

During the last 10 years the knowledge about rostral anterior cingulate cortex (ACC) activity in major depression has substantially increased. Several groups have independently described a relationship between resting activity in this area and response to antidepressant treatment. We have recently confirmed a relationship between resting activity of rostral ACC activity and response in a group of 20 patients with major depression using resting theta activity. In this earlier study regions of interest (ROI) were defined in order to establish regional specificity. Differences between responders and nonresponders were only found in the ACC-ROI, but not in the posterior cingulate region. We have now reanalyzed our data using a whole brain voxelwise approach, in order not to miss any other relevant functional differences. In addition to major differences between responders and nonresponders in the rostral ACC, we have identified a nearby region in the midline orbito-frontal region.     

Freezing of gait in postmortem-confirmed atypical parkinsonism.

The frequency and pathophysiology of freezing of gait (FoG) in atypical parkinsonism is unknown. We analysed the frequency of FoG in postmortem-confirmed atypical parkinsonian disorders (APD) comprising corticobasal degeneration (CBD), dementia with Lewy bodies (DLB), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP). Sixty-six patients with pathologically confirmed APD (CBD, n = 13; DLB, n = 14; MSA, n = 15; PSP, n = 24) formed the basis for a multicenter clinicopathological study. Clinical features at first and last clinical visit were abstracted from patient records on standardized forms following strict instructions. At the first visit (median 36 months after symptom onset), 24% of APD had FoG (CBD, 8%; DLB, 21%; PSP, 25%; MSA, 40%). Logistic regression analysis showed a significant association of FoG and urinary incontinence (P = 0.04) at first visit. At last visit, 47% of APD had FoG (CBD, 25%; PSP, 53%; DLB, 54%; MSA, 54%). Clinicopathological correlation based on routine postmortem examination failed to identify a consistent neuropathological substrate of FoG. This study demonstrates that (1) FoG is common in APD, and (2) urinary incontinence is significantly associated with FoG in these disorders. Whether FoG and urinary incontinence share similar neuropathological substrates remains to be determined by future studies.     

Riluzole therapy in cervical dystonia.

We conducted a 6-week open-label pilot study with blinded video rating of riluzole (50 mg twice a day) in six patients with cervical dystonia (CD) refractory to botulinum toxin A and oral pharmacological treatment. The Tsui rating scale served as primary efficacy measure and improved significantly under riluzole (P = 0.002). In three of six patients, the Tsui score improved by more than 30% with a greater 50% reduction in the head tremor/jerk subscore of the Tsui scale. These data suggest that riluzole may be helpful in a subgroup of patients with disabling CD refractory to other therapies.     

Resource implications for a population-based colorectal cancer screening program in Canada: a study of the impact on colonoscopy capacity and costs in London, Ontario.

OBJECTIVE: Cancer Care Ontario has recommended a population-based colorectal cancer (CRC) screening program using fecal occult blood testing. Patients who test positive should undergo further investigation, preferably colonoscopy. So far, no studies have been performed to quantify the costs or demands on the health care system at the community level. The number of consultations, colonoscopies and polypectomies, and the corresponding direct medical costs generated by the CRC screening program, between 2006 and 2015 in London, Ontario, were estimated using a decision analysis model in comparison with the population health model. METHODS: A faxed survey study was conducted to examine the current CRC screening practice among family physicians in London. Data from the survey and randomized studies were applied to a decision analysis model, which simulated the steps involved in population-based biennial and annual CRC screening between 2006 and 2015. The number of consultations, colonoscopies and polypectomies, and their associated costs were calculated. RESULTS: For a cohort population of 140,000, between 50 and 74 years of age, in 2006 to 2015, it is estimated that an average of 412 consultations, 463 colonoscopies and 174 polypectomies will be performed per 100,000 screen eligible population per year in biennial screening, and double in annual screening, reflecting an average of 8.7% or 17.6% increase annually in outpatient colonoscopies, respectively, compared with 2003. A mean of $285,000 or $562,000 per year would be required to support the extra consultation and endoscopic procedures generated by the biennial or annual screening. CONCLUSION: Population-based fecal occult blood testing screening for CRC appears to be a manageable strategy if a modest increase in endoscopic resources is allocated.     

Trajectory of coronary motion and its significance in robotic motion cancellation.

OBJECTIVES: To characterize remaining coronary artery motion of beating pig hearts after stabilization with an 'Octopus' using an optical remote analysis technique. METHODS: Three pigs (40, 60 and 65 kg) underwent full sternotomy after receiving general anesthesia. An 8-bit high speed black and white video camera (50 frames/s) coupled with a laser sensor (60 microm resolution) were used to capture heart wall motion in all three dimensions. Dopamine infusion was used to deliberately modulate cardiac contractility. Synchronized ECG, blood pressure, airway pressure and video data of the region around the first branching point of the left anterior descending (LAD) coronary artery after Octopus stabilization were captured for stretches of 8 s each. Several sequences of the same region were captured over a period of several minutes. Computerized off-line analysis allowed us to perform minute characterization of the heart wall motion. RESULTS: The movement of the points of interest on the LAD ranged from 0.22 to 0.81 mm in the lateral plane (x/y-axis) and 0.5-2.6 mm out of the plane (z-axis). Fast excursions (>50 microm/s in the lateral plane) occurred corresponding to the QRS complex and the T wave; while slow excursion phases (<50 microm/s in the lateral plane) were observed during the P wave and the ST segment. The trajectories of the points of interest during consecutive cardiac cycles as well as during cardiac cycles minutes apart remained comparable (the differences were negligible), provided the hemodynamics remained stable. Inotrope-induced changes in cardiac contractility influenced not only the maximum excursion, but also the shape of the trajectory. Normal positive pressure ventilation displacing the heart in the thoracic cage was evident by the displacement of the reference point of the trajectory. CONCLUSIONS: The movement of the coronary artery after stabilization appears to be still significant. Minute characterization of the trajectory of motion could provide the substrate for achieving motion cancellation for existing robotic systems. Velocity plots could also help improve gated cardiac imaging.