Introduction: Aligning health systems appropriately to the needs of the elderly is an urgent global priority, according to the WHO. In Canada, ED length of stay has risen 16% for elderly patients in the last year. Agitation requiring chemical restraint is a common, high-risk problem for elderly in the ED. Improving outcomes in this heterogeneous population remain difficult due to inability to effectively identify and evaluate delirium, frailty, multi-morbidity, and incompatibility with the ED system. A data-driven approach to complex health problems is a recognized emerging tool for healthcare innovation. New opportunities for targeted quality improvement in the ED will be uncovered by identifying the clinical characteristics of elderly patients with agitation, and the system process factors that influence their outcomes. Methods: We studied 400 patients in a case-control study at two tertiary-care EDs over five years. Patients were randomly selected if age was greater than 75 years. 200 cases of patients who received an intravenous dose of haloperidol, midazolam and/or lorazepam were selected as a surrogate data marker for having agitation. Controls were randomly matched by age and ED diagnosis. Standardized clinical, systems and process variables were collected. We conducted a univariate analysis. Results: Elderly given intravenous medications for agitation had increased mortality (OR 3.8 CI: 1.6-10.7, p<0.001) and ED length of stay (27 vs. 15 hours, p<0.001). No statistical significance was found in clinical characteristics, CTAS scores, PRISMA7 frailty scores nor sentinel or return visits. There was no statistical difference in median hospital length of stay (8 vs. 6 days, p<0.70). No differences were found in median time from ED physician seeing a patient to first consultant request (73 vs. 83 mins, p=0.75). The largest time intervals contributing to ED length of stay were from first consultant request to hospital request (15 vs. 12 hours, p=0.056) and hospitalization delay (13 vs. 7 hours, p=0.45). Conclusion: Identification of high-risk elderly patients for targeted intervention through a data-driven approach is feasible and informative. Traditional clinical characteristics remain unhelpful in identifying and evaluating outcomes in elderly with agitation. We have identified a process factor that is clinically relevant and pragmatic to evaluate in our ED system. Future research focused on optimizing systems process factors to improve quality of elderly care should be prioritized.

Widespread access to the internet is offering new possibilities for data collection in surveillance. We explore, in this study, the possibility of using an electronic tool to monitor occurrence of the tick vector of Lyme disease, Ixodes scapularis. The study aimed to compare the capacity for ticks to be identified in web-based submissions of digital images/photographs, to the traditional specimen-based identification method used by the provincial public health laboratory in Quebec, Canada. Forty-one veterinary clinics participated in the study by submitting digital images of ticks collected from pets via a website for image-based identification by an entomologist. The tick specimens were then sent to the provincial public health laboratory to be identified by the ‘gold standard’ method using a microscope. Of the images submitted online, 74·3% (284/382) were considered of high-enough quality to allow identification. The laboratory identified 382 tick specimens from seven different species, with I. scapularis representing 76% of the total submissions. Of the 284 ticks suitable for image-based species identification, 276 (97·2%) were correctly identified (Kappa statistic of 0·92, Z = 15·46, P < 0·001). This study demonstrates that image-based tick identification may be an accurate and useful method of detecting ticks for surveillance when images are of suitable quality.

Electronystagmographic recordings were made of oculomotor and vestibular function in II patients with autósomat recessive spastic ataxia of Charlevoix-Saguenay. All had horizontal gaze nystagmus, marked impairment of smooth ocular pursuit and optokinetic nystagmus, and defective fixation suppression of caloric nystagmus. Many had saccadic dysmetria. but saccade velocity was probably unaffected. Abnormallies pointing to brainstem disturbance were sparse. The findings are thought to indicate mainly diffuse cerebellar disease, with particular involvement of vermis and vestibulo-cerebellum.

The plasma distribution of α-keto acids was measured in 26 subjects including 8 patients with Friedreich’s ataxia, 8 with the recessive spastic ataxia of Charlevoix-Saguenay and 10 healthy volunteers. The groups were matched with regards to age, sex, weight and the study was conducted under standardized dietary intake. The results indicate significant differences in α-keto acids distribution between the groups.

Dynamic muscle function was evaluated in nine patients with Friedreich's ataxia (FA) and eight with autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). The measurement of torque throughout maximum voluntary isokinetic knee movements was used to quantitatively describe muscle weakness in the ataxic patients. Both FA and ARSACS patients were shown to have decreased dynamic strength in comparison to normal values during knee extension and flexion movements at 30% /s. In the FA patients a lower torqueproducing capacity was seen in the older patients.

The electromyographic (EMG) activity was recorded in lower extremity muscles during the movements. In the vastus lateralis (VL), deviations from the normal EMG activation pattern were described in both groups of patients. A reduced amplitude in the EMG activity in the medial hamstrings (MH) was seen in the majority of the patients. An index of coactivation was defined by comparing the EMG activity when a muscle lengthened (antagonistic) to the EMG activity when the same muscle shortened (agonistic) during the isokinetic contractions. In comparison to normal values increased coactivation indexes were present in the VL and MH in patients of both groups. The characteristics of dynamic muscle strength and the activation of agonistic and antagonistic muscles described in the present study will provide the basis of evaluation for the effects of therapy in these patients.

A preliminary genealogical investigation of all the known ancestors from the year 1608 of 4 apparently unrelated French Canadian kindreds with Friedreich’s ataxia reveals that the original ataxia gene in the province of Quebec was present within a core of no more than 10 families living in Quebec City in the mid-1600's.

We have studied a large family of which seven members suffer from a progressive disease with onset in the first decade. The first symptoms were gait ataxia and clumsiness in all cases, followed by progressive development of severe distal amyotrophy reminiscent of Charcot-Marie-Tooth disease. In four patients a postural tremor which was relieved by pharmacological agents was also evident in the limbs or head.

Cerebellar atrophy was confirmed on CT scan. Motor nerve conduction velocities were in the low normal range, while sensory nerve conduction was markedly decreased. All patients had impaired proprioception and vibration sense. The laboratory investigation revealed a normal CSF protein level and elevated serum bilirubin.

The patients reported in this study apparently suffer from an original recessive form of spinal and olivocerebellar degeneration associated with a neuronal form of Charcot-Marie-Tooth disease.

Nine cases of Friedreich's ataxia and seven cases of autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) were submitted to neuroradiological procedures to determine the extent of atrophie processes in the central nervous system. All cases had a computerized cerebral tomography and five were studied with pneumencephalo-graphy. The results show a correlation between the two tests and the comparison between Friedreich's ataxia and ARS ACS.

In Friedreich's ataxia, the radiological signs are variable and discrete in most of the cases. In A RSA CS there are constant signs of cerebellar atrophy almost limited to the superior parts of the vermis and anterior lobes.

Neurotransmitter replacement therapy in Alzheimer's Disease is currently being attempted using bethanechol chloride (Urecholine) infused intracerebroventricularly with an Infusaid continuous infusion pump. The rationale of this therapy is based on the severe cortical pre-synaptic cholinergic deficit in the presence of relatively normal post-synaptic muscarinic receptor density. Patients are selected on the basis of strict clinical criteria at a functional stage 4 or 5 of Reisberg. A cortical biopsy at the time of pump and catheter implantation confirms the diagnosis by histological and biochemical examination. Pre-operative, post-operative and serial mental status assessments combined with functional ADL assessments monitor changes in behavior. A 6 months double-blind treatment period is done in every patient, who is then free to continue if he has improved on active treatment. This specific study is part of a multi-centre trial. Other therapeutic trials using somatostatin analogs, such as Sandostatin, could then be done. The biological effects of the latter compound are being studied currently in adult Green Vervet monkeys, prior to its use in Alzheimer patients. Furthermore autoradiography of bethanechol and peptides labeled with 14C administered in these animals by intracerebroventricular infusion will allow a better knowledge of their pharmacological site of action.

A new syndrome of autosomal recessive spastic ataxia has been isolated in the Charlevoix-Saguenay region of Quebec. This syndrome is remarkably homogeneous and includes: spasticity, dysarthria, distal muscle wasting, foot deformities, truncal ataxia, absence of sensory evoked potentials in the lower limbs, retinal striation reminiscent of early Leber's atrophy and the frequent presence (57%) of a prolapse of the mitral valve. Biochemically, many cases show impaired pyruvate oxidation, others have hyperbilirubinaemia and some have low serum β-lipoproteins and HDL apoproteins. These features are similar to those found in trypical Friedreich's ataxia.

To test the physiological significance in vivo of our previous in vitro finding of reduced valine dehydrogenase (VDH) activity inpatients with Friedreich’s Ataxia, we subjected ataxic patients and controls to an oral valine load test (1.0g) and measured the levels of branched chain α-keto acids in the plasma for 24 hours. We demonstrated a significantly higher peak for α-keto isovaleric acid in Friedreich’s Ataxia and a general trend towards higher than control values in all other α-keto acids measured, and at all times in the experiment. These changes are compatible with the postulated defect in regulation of the activity of VDH in this illness, but because of their small amplitude, they also indicate that a VDH – deficiency is not the genetic defect in Friedreich’s A taxia.

Twenty four ataxie patients were investigated with electromyography and nerve conduction studies. They were divided in two groups according to the area they came from, the evolution of the disease, and the clinical signs. Group I patients from the Rimouski area displayed all the clinical and electrophysiological signs of Friedreich's ataxia. Group II comprised patients who presented with a new syndrome known as the autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). Although the clinical evolution was better in the latter, there were more electromyographic signs of denervation and the motor conduction velocities were slower. Both groups showed identical and important abnormalities in sensory nerve conduction.

The results of electrophysiological studies in spastic ataxia have not been reported to our knowledge. They underline the place of spastic ataxia as distinct f rom Friedreich's ataxia, spastic paraplegia, and the known familial neuropathies.

Genetic linkage analysis requires the identification and documentation of large families with many affected members present, preferably in more than one generation. The IMAGE Project has been establishing a population- based Alzheimer disease (AD) registry in the Saguenay - Lac-Saint-Jean region of the Province of Quebec. The population of this region has a well-documented ancestry, with reliable genealogical records (since 1842) computerized by SORER We have recently begun to investigate the pedigrees of selected probands (definite, probable and possible) from the IMAGE registry in order to identify informative pedigrees for genetic linkage analysis. Interviews were carried out with close relatives of the probands (at least one informant per sibship) to identify secondary AD cases. The questionnaires used pertain to the accuracy of genealogical records, to family medical history and to a retrospective diagnosis of AD for people with cognitive deficits. By these means, we have documented a large extended pedigree in which a total of 15 individuals with cognitive deficits were ascertained over three generations. Of these cases, 7 are still living and there is autopsy confirmation in another one. Computer simulations using the program SIMLINK revealed that this is a potentially informative family for linkage analysis. Horizontal extension of the pedigree to second cousins of the proband is now being carried out. This will render the family IMAGE/1 even more informative in genetic linkage analysis studies.

Since the discovery of a significant depletion of acetylcholine in discrete areas of the brain of patients affected by Alzheimer's disease, attempts at symptomatic therapy have concentrated on acetylcholine supplementation, an approach that is based upon the efficacy of dopaminergic supplementation therapy for Parkinson's disease. Choline, then lecithin, used orally, failed to improve symptoms but the hypothesis that long-term choline supplementation might stabilize the course of Alzheimer's disease remains to be tested. Nerve growth factor may also offer that possibility. Bethanechol administered intracerebroventricularly did not help when a fixed dose was used but individual titration of more selective muscarinic agonists may prove more effective. In this article we report that tetrahydroaminoacridine (THA), given together with highly concentrated lecithin, appears to bring improvement in cognition and in functional autonomy using the Mini Mental State and the Rapid Disability Rating Scale-2 respectively, without change in behavior as reflected by the Behave-AD. Double-blind cross-over studies are in progress to establish its efficacy. Improvement in study design and means of assessment of cognition, functional autonomy and behavior have been made possible by these drug trials.

We described a cluster of 8 independent sibships of Friedreich's ataxia in the ShFabien parish of Rimouski and have shown that they are all related within 6 generations. The study of this geographic and genetic isolate permitted the investigation of certain unusual features of the disease such as constant myopia, delayed reaction times to pain, flexor spasms, anda rapid evolution.

Seventeen patients with Friedreich’s ataxia or spastic ataxia were subjected to an urodynamic evaluation. Fifty-three per cent (53%) of the patients presented with urinary symptoms consisting of urgent micturition and urgency incontinence. Cystometric evaluation showed a lack of inhibition of the detrusor in 7 patients (41%). Abnormal electric hyperactivity of the external sphincter was documented in 6 cases (37.5%) by electromyography. Some hypotheses are presented to explain the etiology of these abnormal findings.