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Heredoataxias are a group of genetic disorders with a cerebellar syndrome as the leading clinical manifestation. The current classification distinguishes heredoataxias according to the trait of inheritance into autosomal dominant, autosomal recessive, X-linked, and maternally inherited heredoataxias. The autosomal dominant heredoataxias are separated into spinocerebellar ataxias (SCA1-8, 10-15, 17-23, 25-30, and dentato-rubro-pallido-luysian atrophy), episodic ataxias (EA1-7), and autosomal dominant mitochondrial heredoataxias (Leigh syndrome, MIRAS, ADOAD, and AD-CPEO). The autosomal recessive ataxias are separated into Friedreich ataxia, ataxia due to vitamin E deficiency, ataxia due to Abeta-lipoproteinemia, Refsum disease, late-onset Tay-Sachs disease, cerebrotendineous xanthomatosis, spinocerebellar ataxia with axonal neuropathy, ataxia telangiectasia, ataxia telangiectasia-like disorder, ataxia with oculomotor apraxia 1 and 2, spastic ataxia of Charlevoix-Saguenay, Cayman ataxia, Marinesco-Sjögren syndrome, and autosomal recessive mitochondrial ataxias (AR-CPEO, SANDO, SCAE, AHS, IOSCA, MEMSA, LBSL CoQ-deficiency, PDC-deficiency). Only two of the heredoataxias, fragile X/tremor/ataxia syndrome, and XLSA/A are transmitted via an X-linked trait. Maternally inherited heredoataxias are due to point mutations in genes encoding for tRNAs, rRNAs, respiratory chain subunits or single large scale deletions/duplications of the mitochondrial DNA and include MELAS, MERRF, KSS, PS, MILS, NARP, and non-syndromic mitochondrial disorders. Treatment of heredoataxias is symptomatic and supportive and may have a beneficial effect in single patients.
(1) To examine the variability in diagnosis of mild traumatic brain injury (mTBI) in primary care relative to that of an expert reviewer; and (2) to determine the incidence rate of mTBI in Ontario, Canada.
Potential mTBI cases were identified through reviewing three months of Emergency Department (ED) and Family Physician (FP) health records. Potential cases were selected from ED records using the International Classification of Disease, 9th revision, Clinical Modification and External Cause codes and from all FPs records for the time period. Documented diagnoses of mTBI were compared to expert reviewer diagnosis. Incidence of mTBI was determined using the documented diagnoses and data from hospital catchment areas and population census.
876 potential mTBI cases were identified, 25 from FP records. Key indicators of mTBI were missing on many records (e.g., 308/876 records had Glasgow Coma Scale (GCS) scores). The expert reviewer disagreed with the documented diagnosis in 380/876 cases (kappa=0.19). The expert reviewer was more likely to give a diagnosis if the GCS was 13-14, if there was documented loss of consciousness and/or post-traumatic amnesia, and/or if there was pathology found on an acute brain scan. Calculated incidence rates of hospital-treated mTBI were 426 or 535/100,000 (expert review - hospital diagnosis). Including family physician cases increased the rate to 493 or 653/100,000.
Health record documentation of key indicators for mTBI is often lacking. Notwithstanding, some patients with mTBI appear to be missed or misdiagnosed by primary care physicians. A more comprehensive case definition resulted in estimated incidence rates higher than previous reports.
To evaluate the incidence of hypoglycemia, hyperglycemia and blood glucose (BG) variability in brain-injured patients and their association with clinical outcomes.
Retrospective cohort study of brain-injured patients admitted to an 11- bed neurosciences intensive care unit (ICU) from January 1 to December 31, 2003.
We included 606 patients. Mean age was 52.3 years, 60.6% were male, 11.9% had diabetes mellitus, and 64% were post-operative. Seventy-five (12.4%) received intensive insulin therapy (IIT) for a median (IQR) 72 (24-154) hours. Hypoglycemia and hyperglycemia occurred in 4.6% (96.4% receiving IIT) and 9.6% (77.6% receiving IIT). Median number of episodes per patient was 3 (75% with ≥2) and 4 (81% with ≥2) for hypoglycemia and hyperglycemia. Variable glycemic control occurred in 3.8% (100% receiving IIT) with median number of 13 episodes per patient. In-hospital mortality was 16.7%, median (IQR) ICU and hospital lengths of stay were 2 (1-5) and 8 (3-19) days. Hypoglycemia, hyperglycemia and BG variability showed non-significant but consistent associations with hospital mortality and prolonged lengths of ICU and hospital stay. The rate of recurrence of episodes showed stronger and significant associations with outcome, in particular for BG variability and hyperglycemia.
Hypoglycemia, hyperglycemia and BG variability are relatively common in brain-injured patients and are associated with IIT. An increased frequency of episodes, in particular for BG variability and hyperglycemia, was associated with greater risk of both hospital death and prolonged duration of stay.
We examined the effects of various exercise intensities on recovery from middle cerebral artery occlusion (MCAO) in rats.
First, we administered a 120-minute left MCAO to male Sprague-Dawley rats and randomly assigned them to one of four groups: no exercise (Group 1), mild exercise (Group 2), moderate exercise (Group 3), and severe exercise (Group 4). Then, we trained the rats for 30 min per day for one week or two weeks. We used a five-point neurological evaluation scale to measure neurological deficits 1-day, 4-days, 7-days, 10-days and 14-days after MCAO and measured infarct volume by use of 2% 2,3,4-triphenyltetrazolium chloride in exercised brains. We also performed immunohistochemistry analysis of the brain to observe reactive astrocytosis at the peri-infarct region.
Neurological examination indicated that Group 2 and 3 recovered better than Group 1 after one week and two weeks (p<0.05). Moreover, Group 2 and 3 had reduced brain infarct volume compared with Group 1 after one week (p<0.05). There were no significant differences between Group 4 and Group 1. The thickness of the peri-infarct astrocytosis was significantly reduced in Group 4 relative to Group 1 after one week. There was a significant negative correlation between the extent of reactive astrocytosis and neurological recovery (r= -0.648, p<0.01).
This study demonstrates that mild to moderate exercise that begins soon after induced cerebral ischemia promotes recovery and that astrocytes may have an important role in the recovery process.
Current ‘standard of care’ for patients presenting with a ‘high-risk’ TIA varies, with use of several outpatient and inpatient approaches. We describe the clinical outcomes and costs for high risk TIA patients who received care in a ‘rapid evaluation unit’, and compare these to a historical ‘high-risk’ cohort.
The study cohort was comprised of patients with TIA admitted to a ‘rapid evaluation unit’ during the period March 2002 to April 2003. The comparison cohort was established by screening Calgary Health Region ER discharge records to identify all patients presenting with a diagnosis of TIA during the year 2000. A ‘high-risk standard care cohort’ was then identified based on the clinical admission criteria used to select patients for the rapid evaluation unit. Outcomes (stroke within 90 days, death) and costs were identified using chart review and provincial administrative data.
The early risk of stroke in the high risk standard care group (392 patients) was 9.7%, compared to 4.7% in the rapid evaluation cohort (189 patients) (p=0.05). Median 1-year costs post TIA were CAN$8360 for patients in the rapid evaluation cohort, compared with CAN$4820 for patients in the high risk standard care group (p<0.001).
The risk of early stroke was lower for patients in the rapid evaluation cohort compared to the high risk standard care cohort, suggesting that the use of rapid evaluation programs in patients with TIA at high risk of stroke may be beneficial, but incur greater costs over the course of the first year.
The computed tomogram angiography (CTA) ‘spot sign’ describes foci of intralesional enhancement associated with hematoma expansion in primary intracerebral hemorrhage patients. A consistent radiological definition is required for two proposed recombinant Factor VIIa trials planning patient dichotomization according to ‘spot sign’ presence or absence. We propose radiological criteria for diagnosis of the CTA ‘spot sign’ and describe different morphological patterns.
Material and Methods:
A prospective cohort of 36 consecutive patients presenting with primary intracerebral hemorrhage (ICH) were enrolled in a multicenter collaborative study, and have been included for the present analysis. Three reviewers analyzed the CTA studies in a blinded protocol. Analysis of specific ICH and ‘spot sign’ features was performed including prevalence, number, size, location, morphology and Hounsfield unit density.
Twelve of thirty-six patients (33%) demonstrated a total of 19 enhancing foci consistent with the CTA ‘spot sign’. Mean maximal axial ‘spot sign’ dimension was 3.7±2.2 mm and mean density was 216±57.7 HU. No significant differences in age or blood pressure (p=0.7), glucose (p=0.9), INR/PTT (p=0.3 and 0.4) or hematoma location (p=0.3) were demonstrated between patients with or without the ‘spot sign’. Consensus definition and classification criteria for the CTA ‘spot sign’ are proposed.
The ‘spot sign’ is defined as spot-like and/or serpiginous foci of enhancement, within the margin of a parenchymal hematoma without connection to outside vessels. The ‘spot sign’ is greater than 1.5 mm in maximal dimension and has a Hounsfield unit density at least double that of background hematoma density.
The onset of progressive cerebellar ataxia in early childhood is considered a key feature of ataxiatelangiectasia (A-T), accompanied by ocular apraxia, telangiectasias, immunodeficiency, cancer susceptibility and hypersensitivity to ionizing radiation.
We describe the clinical features and course of three Mennonite children who were diagnosed with A-T following the completion of therapy for lymphoid malignancies.
Prior to cancer therapy, all had non-progressive atypical neurological abnormalities, with onset by age 30 months, including dysarthria, dyskinesia, hypotonia and/or dystonia, without telangiectasias. Cerebellar ataxia was noted in only one of the children and was mild until his death at age eight years. None had severe infections. All three children were “cured” of their lymphoid malignancies, but experienced severe adverse effects from the treatments administered. The two children who received cranial irradiation developed supratentorial primitive neuroectodermal tumors of the brain, an association not previously described, with fatal outcomes.
The range of neurological presentations of A-T is broad. Ataxia and telangiectasias may be minimal or absent and the course seemingly non-progressive. The diagnosis of A-T should be considered in all children with neuromotor dysfunction or peripheral neuropathy, particularly those who develop lymphoid malignancies. The consequences of missing the diagnosis may be dire. Radiation therapy and radiomimetic drugs should be avoided in individuals with A-T.
Linear accelerator based stereotactic radiation therapy (SRT) has been used for the treatment of pituitary tumours; however, little is known concerning the use of this modality for the treatment of patients with acromegaly. We have prospectively studied the short-term outcome of SRT in 12 acromegaly patients who failed to achieve biochemical remission despite surgery and/or pharmacologic therapy.
We identified all patients who had biochemically uncontrolled acromegaly and were treated with SRT between April 2003 and December 2006. All patients were followed prospectively based on a pre-defined protocol that included Goldman visual field examination, MRI of the sella, and pituitary hormone testing at 3, 6, 12 months, and then yearly.
A total of 12 patients with acromegaly were treated with SRT. There were 9 females and the median age of the group was 50 years. The median follow-up was 28.5 months during which time the mean tumor volume decreased by 40%, the median GH fell from 4.1 μg/L to 1.3 μg/L (p=0.003) and the median IGF-1 dropped more than half from 545.5 μg/L to 260.5 μg/L (p=0.002). Four patients achieved normal, while an additional 2 achieved near-normal, IGF-1 levels. One patient was able to discontinue and two were able to reduce their acromegaly medications while maintaining a normal IGF-1. A new pituitary hormonal deficit was found at 24 months in one patient who developed hypoadrenalism requiring corticosteroid replacement.
Based on our early experience, we believe that SRT should be considered in treating patients with uncontrolled acromegaly.
To study the effect on quality of life (QOL) of a seizure attack while driving in persons with epilepsy (PWE).
From four provincial and eight university hospitals in Thailand, we enrolled epileptic patients who drove a car or motorcycle or used to drive. The SF-36 questionnaire was used to evaluate QOL. The mean SF-36 score for all dimensions was calculated and compared with patients who either had or did not have a seizure attack while driving and in those who either had or had not been involved in a traffic accident while driving.
We had 245 adult PWE who drove a car or motorcycle or used to drive. Of these, 69 cases (28%) had a seizure attack whilst driving. Over half (36/69; 57%) had had seizure-related accidents, most of which were mild but about 20% needed hospitalization. PWE having a seizure attack while driving had a significantly lower QOL in four of the eight categories compared with patients who had not. PWE who had a seizure-related accident had a significantly lower mean value in the vitality category than those who did not.
Seizure attacks while driving diminished QOL in PWE even though they only suffered minor injuries. Driving as a QOL issue should be discussed with patients. A good public transportation system would ease the need to drive.