Ictal aphasia in LGI1-related autosomal dominant epilepsy with auditory features.

Autosomal dominant epilepsy with auditory features (OMIM 600512) is characterised by focal seizures with distinctive auditory auras and/or ictal aphasia. We describe a 17-year-old girl with recurrent attacks of ictal aphasia and rare nocturnal convulsions. She had a four-generation paternal family history of epilepsy. Her father and aunt perceived bells ringing at the onset of seizures. Sequence analysis of the leucine-rich glioma-inactivated 1 (LGI1) gene identified a novel heterozygous variant in the proband and her father. LGI1-related genetic epilepsy has a benign clinical course with a favourable response to anti-seizure medications. Auditory or vertiginous seizures may be mistaken for peripheral audio-vestibular symptoms, while complex auditory ictal symptoms may be misattributed to primary psychiatric disorders. Recognising this distinctive inherited syndrome should prompt targeted analysis of the LGI1 gene.

A clinical, molecular genetics and pathological study of a FTDP-17 family with a heterozygous splicing variant c.823-10G>T at the intron 9/exon 10 of the MAPT gene.

We report the first clinical-radiological-genetic-molecular-pathological study of a kindred with c.823-10G>T MAPT intronic variant (rs63749974) associated with frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). We describe the clinical spectrum within this family and emphasize the association between MAPT gene variants and motor neuron disease. This report of a second family with FTDP-17 associated with c.823-10G>T MAPT variant strongly supports pathogenicity of the variant and confirms it is a 4-repeat (4R) tauopathy. This intronic point mutation, probably strengthens the polypyrimidine tract and alters the splicing of exon 10 (10 nucleotides into intron 9) close to the 3' splice site.

Antibody-Negative Paraneoplastic Limbic Encephalitis, Parkinsonism, Hypothermia, and Narcolepsy Associated with Endometrial Carcinoma.

BACKGROUND: We describe the clinical and neuropathological features of a patient with T-cell-mediated paraneoplastic limbic encephalitis, parkinsonism, hypothermia, and narcolepsy-like presentation associated with endometrial carcinoma. OBJECTIVES: This patient with prominent parkinsonism and narcolepsy broadens the phenotype of known paraneoplastic syndromes and demonstrates the importance of investigation for occult malignancy even in the absence of paraneoplastic antibodies. METHODS: This is a case report with diagnosis confirmed at postmortem. RESULTS: Paraneoplastic antibodies were not detected. The initial improvement with immunosuppression was short lived, and postmortem neuropathological examination demonstrated encephalitis with predominant T-cell infiltration affecting the hypothalamus and extending to the brainstem, suggestive of a paraneoplastic syndrome. CONCLUSIONS: Although the possibility of a novel antibody cannot be ruled out, consideration must also be given to recent demonstration of purely T-cell-mediated neuronal destruction in the context of paraneoplastic syndromes.

Prognostic value of colonic and peripheral venous lactate measurements in horses with large colon volvulus.

OBJECTIVE: To determine the prognostic value of (1) colonic venous lactate or peripheral lactate values obtained before and after manual correction of a large colon volvulus and (2) a combination of variables including pelvic flexure biopsy. STUDY DESIGN: Prospective clinical study. ANIMALS: Forty adult horses in which large colon volvulus was diagnosed intraoperatively. METHODS: Colonic venous, peripheral venous, and arterial blood samples were collected to measure lactate values before and after manual correction. Mucosal biopsy samples were obtained in cases that underwent enterotomy or colonic resection and anastomosis. Interstitium to crypt (I:C) ratio and hemorrhage scores were measured. Optimal cutoff values were determined by receiver operator curve analysis, and associations between variables and short-term outcome were determined by univariable regression. Short-term survival was defined as horses being discharged from the hospital. P ≤ .05 was considered significant. RESULTS: No association was found between colonic venous lactate values before (P = .011) or after (P = .201) manual correction of large colon volvulus and determination of short-term outcome. Peripheral venous lactate at admission ≥3.2 mmol/L and after manual correction ≥5 mmol/L, arterial lactate postmanual correction ≥3.53 mmol/L, and histomorphometric measurements of mucosal hemorrhage ≥3 and I:C ratio > 1 were associated with poor short-term outcome. CONCLUSION: Peripheral lactate values, histomorphometric measures of I:C ratio, and hemorrhage score provided prognostic information that could help guide recommendations made to owners. CLINICAL SIGNIFICANCE: Peripheral lactate values after manual correction provide important intraoperative diagnostic information to assist in predicting case outcome in the operative and immediately postoperative period.

The benefits of a Neurogenetics clinic in an adult Academic Teaching Hospital.

Genetics is the backbone of Neurology, where a number of disorders have a genetic aetiology and are complex, requiring a dedicated Neurogenetics clinic. Genetics in the Republic of Ireland is under-resourced, with the lowest number of consultants per million of population in Europe. In November 2014, we established the monthly adult Neurogenetics clinic in Ireland, staffed by 2 consultants and 2 registrars from each speciality. We see patients with complex rare neurological conditions that may potentially have an underlying genetic basis, in the presence or absence of a family history. We performed a retrospective cohort analysis, reviewing symptoms and work-up data. Twenty-seven patients attended a pilot clinic over 12 months. Conditions encountered included Parkin-related PD, leucodystrophy, ataxia, fronto-temporal lobar degeneration, spinocerebellar ataxia type 6 (SCA6) and ataxia-telangiectasia. Identification of pathogenic mutations directed screening, treatment and facilitated onward genetic counselling (n = 10, 33%). A number of novel mutations were identified in MAPT gene ("missing tau mutation" McCarthy et al., Brain, 2015), SLCA1 gene and GRN (progranulin). Phenotypic features not previously reported were seen; e.g. writer's cramp in SCA6; paroxysmal myoclonus in the glucose transporter protein type 1 (GLUT1) deficiency. Breast cancer screening for ATM mutations carriers and referral to international experts in two undiagnosed patients were arranged. The establishment of a Neurogenetics clinic has addressed a gap in service and allowed identification of rare and atypical diagnoses.

An evaluation of the role of environmental factors in the disease penetrance of cervical dystonia.

BACKGROUND: Adult onset primary torsion dystonia (AOPTD) is a poorly penetrant autosomal dominant disorder; most gene carriers are non-manifesting despite having reached an adequate age for penetrance. It is hypothesised that genetic, epigenetic and environmental factors may exert protective or deleterious effects on penetrance of AOPTD. By examining environmental exposure history in cervical dystonia patients and their similarly aged unaffected siblings we aimed to determine the role of previous environmental exposures in relation to disease penetrance. METHODS: A case-control study of 67 patients with cervical dystonia and 67 of their age-matched unaffected siblings was performed. Past environmental exposures were assessed using a detailed 124-question standardised questionnaire. RESULTS: By univariate analysis, cervical dystonia patients, compared to their unaffected siblings, had an increased frequency of a history of car accidents with hospital attendance (OR 10.1, 95% CI 2.1 to 47.4, p=0.004) and surgical episodes (OR 6.5, 95% CI 1.76 to 23.61, p=0.005). Following multivariate analysis, car accidents with hospital attendance (OR 7.3, 95% CI 1.4 to 37.6, p=0.017) and all surgical episodes (OR 4.9, 95% CI 1.24 to 19.31, p=0.023) remained significantly associated with case status. CONCLUSIONS: Cervical dystonia patients had a history, prior to symptom onset, of significantly more frequent episodes of surgery and of car accidents with hospital attendance than their age-matched unaffected siblings. Soft tissue trauma appears to increase risk of development of cervical dystonia in genetically predetermined individuals.

Pediatric ovarian torsion: case series and review of the literature.

BACKGROUND: Ovarian torsion in children is an uncommon cause of acute abdominal pain but mandates early surgical management to prevent further adnexal damage. The clinical presentation mimics other pathologies, such as appendicitis. We sought to more completely characterize ovarian torsion with respect to pain and ancillary studies, such as urinalysis. METHODS: We performed a retrospective review of hospital charts of all patients aged 0-18 years with a diagnosis of ovarian torsion at the Children's Hospital at London Health Sciences Centre, in London, Ont., from 1993 to 2008. RESULTS: We analyzed 13 charts of patients aged 7 months to 18 years. Most patients presented with peripheral leukocytosis, vomiting and right lower quadrant pain that did not radiate or migrate. On urinalysis, about half the patients demonstrated pyuria without bacteruria. Pelvic ultrasound revealed an ovarian cyst on the same side of the pain in 11 of 13 patients. Most were found to have a hemorrhagic cyst or ovary and underwent salpingo-oophorectomy or cystectomy within 48 hours of presentation. CONCLUSION: Ovarian torsion should be considered in any female child with acute onset lower abdominal pain accompanied by vomiting. Pain can be characterized as constant or colicky, but unlike with appendicitis, does not typically migrate. Sterile pyuria is found in a substantial proportion of cases. Ultrasound is the most useful initial diagnostic modality, but the absence of flow on Doppler imaging is not always present. Conservative management with detorsion and oophoropexy is recommended.

Direct interactions of ABA-insensitive(ABI)-clade protein phosphatase(PP)2Cs with calcium-dependent protein kinases and ABA response element-binding bZIPs may contribute to turning off ABA response.

Abscisic acid (ABA) signaling via the pyrabactin-resistant and related (PYR/PYL/RCAR) receptors begins with ABA-dependent inactivation of the ABA-insensitive(ABI)-clade protein phosphatases(PP)2Cs, thereby permitting phosphorylation and activation of the Snf1-related (SnRK)2 clade of protein kinases, and activation of their downstream targets such as ABA-response element binding basic leucine zipper (bZIP) transcription factors (ABF/AREB/ABI5 clade). Several of these are also activated by calcium-dependent protein kinases such as CPK11. Turning off ABA response requires turnover and/or inactivation of these transcription factors, which could result from their dephosphorylation. To address the hypothesis that the ABI-clade PP2Cs regulate the bZIPs directly, in addition to their indirect effects via SnRKs, we have assayed interactions between multiple members of the ABF/AREB clade and the PP2Cs by yeast two-hybrid, in vitro phosphatase, and bimolecular fluorescence complementation assays. In addition, we have expanded the list of documented specific interactions among these bZIP proteins and the kinases that could activate them and found that some PP2Cs can also interact directly with CPK11. These studies support specific interactions among kinases, phosphatases and transcription factors that are co-expressed in early seedling development.

Strangulating intestinal obstructions in four captive elephants (Elephas maximus and Loxodonta africana).

Three captive-born (5-day-old, 8-day-old, and 4-yr-old) Asian elephants (Elephas maximus) and one captive-born 22-yr-old African elephant (Loxodonta africana) from three private elephant facilities and one zoo in the United States presented with depression, anorexia, and tachycardia as well as gastrointestinal signs of disease including abdominal distention, decreased borborygmi, tenesmus, hematochezia, or diarrhea. All elephants showed some evidence of discomfort including agitation, vocalization, or postural changes. One animal had abnormal rectal findings. Nonmotile bowel loops were seen on transabdominal ultrasound in another case. Duration of signs ranged from 6 to 36 hr. All elephants received analgesics and were given oral or rectal fluids. Other treatments included warm-water enemas or walking. One elephant underwent exploratory celiotomy. Three animals died, and the elephant taken to surgery was euthanized prior to anesthetic recovery. At necropsy, all animals had severe, strangulating intestinal lesions.

GAD antibody positive paraneoplastic stiff person syndrome in a patient with renal cell carcinoma.

Stiff person syndrome (SPS) is an unusual cause of muscle rigidity and spasms. It is believed to have an autoimmune pathogenesis and is associated with autoantibodies to glutamic acid decarboxylase (GAD). Paraneoplastic SPS (PSPS) has been described mainly in relation to breast cancer and is associated with antibodies to amphiphysin. Few reports of PSPS document the finding of GAD autoantibodies. We present the first reported case of anti-GAD positive PSPS in a 53-year-old male with occult renal carcinoma. Clinical benefit was marked following nephrectomy and intravenous immunoglobulin treatment. Renal carcinoma should be considered in patients with SPS.

Screening for iron deficiency anemia in at risk children in the pediatric emergency department: a survey of Canadian pediatric emergency department physicians.

OBJECTIVE: To determine the attitudes and reported practices of physicians regarding screening for iron deficiency anemia in at-risk children in pediatric emergency departments (PEDs) across Canada. METHODS: A standardized survey was mailed to 183 PED physicians at 10 tertiary care PED across Canada. The practices and attitudes regarding screening for iron deficiency anemia were collected via a questionnaire consisting of single select closed-ended items and items which required ranking in order of importance. RESULTS: Sixty-one percent (111/183) of physicians responded to the survey. Ninety-six percent of respondents do not routinely screen for iron deficiency anemia. One third of respondents believed that screening for iron deficiency anemia in the PED is possible. The remaining stated lack of time, difficulty with follow-up, it not being an emergent issue and cost as prohibitive factors. One third of participants stated that 21% to 40% of the pediatric patients seen in their PED did not have a primary care physician. The main considerations in deciding on whom to perform venipuncture were based on dietary history and physical examination with a history of consumption of milk greater than 24 ounces per day (94%) and conjunctival or skin pallor (97%, 94%, respectively) selected as the most important items. CONCLUSION: The results of this study indicate that Canadian PED physicians are not routinely screening for iron deficiency anemia, although they demonstrate knowledge of the risk factors for iron deficiency anemia and recognize the importance of diagnosis and treatment to prevent long-term morbidity.

Reverse quality management: developing evidence-based best practices in health emergency management.

The British Columbia Ministry of Health's Framework for Core Functions in Public Health was the catalyst that inspired this review of best practices in health emergency management. The fieldwork was conducted in the fall of 2005 between hurricane Katrina and the South Asia earthquake. These tragedies, shown on 24/7 television news channels, provided an eyewitness account of disaster management, or lack of it, in our global village world. It is not enough to just have best practices in place. There has to be a governance structure that can be held accountable. This review of best practices lists actions in support of an emergency preparedness culture at the management, executive, and corporate/governance levels of the organization. The methodology adopted a future quality management approach of the emergency management process to identify the corresponding performance indictors that correlated with practices or sets of practices. Identifying best practice performance indictors needed to conduct a future quality management audit is described as reverse quality management. Best practices cannot be assessed as stand-alone criteria; they are influenced by organizational culture. The defining of best practices was influenced by doubt about defining a practice it is hoped will never be performed, medical staff involvement, leadership, and an appreciation of the resources required and how they need to be managed. Best practice benchmarks are seen as being related more to "measures" of performance defined locally and agreed on by 2 or more parties rather than to achieving industrial standards. Relating practices to performance indicators and then to benchmarks resulted in the development of a Health Emergency Management Best Practices Matrix that lists specific practice in the different phases of emergency management.

Performance after partial arytenoidectomy without mucosal closure in 27 Thoroughbred racehorses.

OBJECTIVE: To examine the effect of partial arytenoidectomy without mucosal closure on postoperative racing performance and long-term complications in Thoroughbred racehorses treated for laryngeal hemiplegia, arytenoid chondropathy, or failed laryngoplasty. STUDY DESIGN: Retrospective study. ANIMALS: Twenty-seven Thoroughbred racehorses. METHODS: Medical records of Thoroughbred racehorses that had partial arytenoidectomy without mucosal closure between 1992 and 2002 were reviewed. Horses were divided into groups: horses that had not raced (Group 1) and those that had raced (Group 2) before surgery. Lifetime race records were compared between groups. A standard starts index (SSI) and performance index (PI) were used for Groups 1 and 2, respectively, to objectively evaluate each horse's postoperative performance. Telephone interviews of owners and trainers were used for subjective performance evaluation and to determine prevalence of long-term complications. RESULTS: Eleven (61%) Group 1 and 7 (78%) Group 2 horses raced and earned money after surgery. All Group 1 horses that raced performed at a level lower than the national average. Only 1 Group 2 horse had an improved PI score postoperatively. CONCLUSIONS: Thoroughbred racehorses have a fair prognosis for racing successfully after partial arytenoidectomy without mucosal closure. CLINICAL RELEVANCE: This technique may be a practical alternative to primary mucosal closure, would decrease surgical time, and avoid some problems reported with primary mucosal closure.

Functional promoter region polymorphism of the proinflammatory chemokine IL-8 gene associates with Parkinson's disease in the Irish.

Parkinson's disease (PD) is one of the most prevalent neurodegenerative disorders and is characterized by the progressive loss of dopamine neurons in the substantia nigra. There is increasing evidence to suggest the inflammatory response of the brain contributes to the pathogenesis of PD. This study investigated the frequency of polymorphism located in the critical promoter region of the proinflammatory cytokine genes: interleukin (IL)-2, IL-6, IL-8, and tumor necrosis factor alpha (TNF-alpha) within a cohort of patients with PD in comparison to a group of healthy elderly individuals. No association was observed for single nucleotide polymorphism in the promoter regions of the IL-2, IL-6, and TNF-alpha genes. The single nucleotide polymorphism in the chemokine IL-8 gene was observed to associate with PD and appeared to be independent of age at onset. This association further supports the theory that the proinflammatory response in the brains of patients with PD plays a role in the pathogenesis of the disease and warrants further investigation into the role of chemokines in the brain, and a more detailed analysis of the genetics involved in the immune response of the brain.