Men with FMR1 premutation alleles of less than 71 CGG repeats have low risk of being affected with fragile X-associated tremor/ataxia syndrome (FXTAS)

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset condition characterised by cerebellar ataxia and intention tremor, usually found in individuals with FMR1 premutation alleles (PM—CGG expansion of 55–199 repeats). Population studies estimate that between 1 in 250 and 1 in 1600 men have a PM, with up to 45% of these men suggested to develop FXTAS by age 80. We used a Bayesian approach to compare the probability of finding a specific PM genotype in an ataxia population to a population control group and found an estimated penetrance of <1% (0.031%; CI 0.007% to 0.141%) for men with ≤70 CGGs. These findings suggest that men with a PM of ≤70 CGGs, who comprise the vast majority of those with a PM, have a much lower risk of being affected with FXTAS than previously suggested. This is an issue of growing importance for accurate genetic counselling, as those with a PM of ≤70 CGGs are increasingly detected through community carrier screening or neurodevelopmental assessment programmes.

Aspergillus flavus as a surprise space occupying lesion in an immunocompetent pediatric patient

Background Fungal infections of the CNS are almost always a clinical surprise. Aspergillus species although ubiquitous are more frequently observed in immuno-compromised individuals upon inhalation of conidia. Most of the fungal infections which happen in humans are opportunistic, mostly due to immunocompromised host. Case description We present the case of a 14-year-old boy who presented to the Emergency Department of Aga Khan University Hospital, Karachi, with complaints of right-sided weakness of the body. This was a rapid-onset condition which was associated with gait disturbances and multiple episodes of vomiting. MRI head showed encapsulated Space Occupying Lesion with puss in the left frontal lobe with surrounding edema. The patient was planned for a craniotomy to remove an intracerebral abscess. Histopathology report revealed the presence of chronic granulomatous inflammation with necrosis and numerous septate hyphae. A fungus culture was run which confirmed the presence of heavy colonies of Aspergillus flavus. Conclusion Fungal infections of the central nervous system are almost always a clinical surprise, have a subtle presentation and mistaken often as meningitis, brain abscess, or tumor. Any suspected lesion once removed should be sent for biopsy to rule out the presence of any fungal infection.

ARDS: acute respiratory distress syndrome

Respiratory distress is a common presentation in an emergency and critical care setting. Acute respiratory distress syndrome (ARDS) is an acute onset condition where the lungs cannot provide the patient's vital organs with enough oxygen. ARDS can occur as a result of several underlying triggers. It is important that veterinary nurses know what to look out for in these patients, and how to appropriately nurse them to ensure they are not compromised further.

Evidence of B Cell Clonality and Investigation Into Properties of the IgM in Patients With Schnitzler Syndrome

The Schnitzler Syndrome (SchS) is an acquired, autoinflammatory condition successfully treated with IL-1 inhibition. The two main defining features of this late-onset condition are neutrophilic urticarial dermatoses (NUD) and the presence of an IgM monoclonal component. While the former aspect has been extensively studied in this disease setting, the enigmatic paraproteinaemia and its potential consequential effects within SchS, has not previously been thoroughly addressed. Previous studies analyzing clonal B cell repertoires have largely focused on autoimmune disorders such as Systemic Lupus Erythematous (SLE) and hematological malignancies such as Chronic Lymphocytic Leukaemia (CLL), where B-cell clonality is central to disease pathology. The present study uses next-generation sequencing to provide detailed insight into aspects of B cell VDJ recombination and properties of the resulting immunoglobulin chains. An overview of IgH regional dynamics in 10 SchS patients, with a particular focus on CDR3 sequences and VDJ gene usage is reported, highlighting the presence of specific B cell expansions. Protein microarray detected a substantial proportion of autoreactive IgM to nuclear target proteins, though a single universal target was not identified. Together, these genetic and functional findings impart new understanding into this rare disorder.

Identifying new-onset conditions and pre-existing conditions using lookback periods in Australian health administrative datasets

Background The condition onset flag (COF) variable was introduced into the hospitalization coding practice in 2008 to help distinguish between the new and pre-existing conditions. However, Australian datasets collected prior to 2008 lack the COF, potentially leading to data waste. The aim of this study was to determine if an algorithm to lookback across the previous admissions could make this distinction. Methods All patients requiring kidney replacement therapy (KRT) identified in the Australia and New Zealand Dialysis and Transplant Registry in New South Wales, South Australia and Tasmania between July 2008 and December 2015 were linked with hospital admission datasets using probabilistic linkage. Three different lookback periods entailing either one, two or three admissions prior to the index admission were investigated. Conditions identified in an index admission but not in the lookback periods were classified as a new-onset condition. Conditions identified in both the index admission and the lookback period were deemed to be pre-existing. The degrees of agreement were determined using the kappa statistic. Conditions examined for new onset were myocardial infarction, pulmonary embolism and pneumonia. Conditions examined for prior existence were diabetes mellitus, hypertension and kidney failure. Secondary analyses evaluated whether the conditions identified as pre-existing using COF were captured consistently in the subsequent admissions. Results 11 140 patients on KRT with 69 403 admissions were analysed. Lookback over a single admission interval (Period 1) provided the highest rates of true positives with COF for all three new-onset conditions, ranging from 89% to 100%. The levels of agreement were almost perfect for all conditions (k = 0.94–1.00). This was consistent across the different time eras. All lookback periods identified additional new-onset conditions that were not classified by COF: Lookback Period 1 picked up a further 474 myocardial infarction, 84 pulmonary embolism and 1092 pneumonia episodes. Lookback Period 1 had the highest percentage of true positives when identifying the pre-existing conditions (64–80%). The level of agreement was moderate to strong and was similar across the time eras. Secondary analysis showed that not all pre-existing conditions identified using COF carried forward to the subsequent admission (61–82%) but increased when looking forward across &gt;1 admission (87–95%). Conclusion The described algorithm using a lookback period is a pragmatic, reliable and robust means of identifying the new-onset and pre-existing patient conditions, thereby enriching the existing datasets predating the availability of the COF. The findings also highlight the value of concatenating a series of hospital patient admissions to more comprehensively adjudicate the pre-existing conditions, rather than assessing the index admission alone.

COMPARISON STUDY BETWEEN ULTRASOUND AND SHORTWAVE AS A PHYSIOTHERAPY TREATMENT IN FROZEN SHOULDER CONDITION

Background: Frozen shoulder is a spontaneous onset condition, disabling and sometimes severely painful condition accompanied by progressive limitation of both active and passive movements of shoulder joint. It is one of the important conditions that could be treated by physiotherapy. Methods: Patients attending day clinic department and physiotherapy units in AL-Yarmouk Teaching Hospital in Baghdad/Iraq. A prospective study covered 94 adult patients. Results: Half (50.0%) of the sample were in the old age group (56-70) year. Female more than male (55.3%, 44.7% respectively), more than half of the patients 56.4% have right sided affected. There was no significant difference in the results between the two methods of treatment (p = 0.512). The improvement rate 57.8% is higher among those with mild degree of stiffness, although there was no significant difference between the three degrees of stiffness (p = 0.185). Conclusions: Frozen shoulder is a disabling condition and recovery needs a long-term process. Many physiotherapy options are available for the management, but there is still no consensus among the rheumatologist regarding which therapeutic option is superior. In this study both ultrasound and short-wave therapies have no difference in the outcome of frozen shoulder management.

Molecular and Cellular Mechanisms Affected in ALS

Amyotrophic lateral sclerosis (ALS) is a terminal late-onset condition characterized by the loss of upper and lower motor neurons. Mutations in more than 30 genes are associated to the disease, but these explain only ~20% of cases. The molecular functions of these genes implicate a wide range of cellular processes in ALS pathology, a cohesive understanding of which may provide clues to common molecular mechanisms across both familial (inherited) and sporadic cases and could be key to the development of effective therapeutic approaches. Here, the different pathways that have been investigated in ALS are summarized, discussing in detail: mitochondrial dysfunction, oxidative stress, axonal transport dysregulation, glutamate excitotoxicity, endosomal and vesicular transport impairment, impaired protein homeostasis, and aberrant RNA metabolism. This review considers the mechanistic roles of ALS-associated genes in pathology, viewed through the prism of shared molecular pathways.

Aspergillus Flavus as a Surprise CNS Space Occupying Lesion in an Immunocompetent Pediatric Patient

Background: Fungal infections of the CNS are almost always a clinical surprise. Aspergillus species although ubiquitous are more frequently observed in immuno-compromised individuals, upon inhalation of conidia. Most of the fungal infections which happen in humans are opportunistic- in an immunocompromised host. However, we report the case of CNS fungal infection in a healthy child, without any co-morbidities, trauma, or medico-surgical intervention- which could have been the nidus of infection. Case Presentation: We present the case of a 14 year old boy who presented to our institute’s emergency department with primary concern of right sided body hemiparesis since twenty-four hours. This was a rapid-onset condition which was associated with gait disturbances and multiple episodes of vomiting. An MRI of the head showed encapsulated Space Occupying Lesion in the left frontal lobe with surrounding edema. The patient was planned for craniotomy to remove the intracerebral abscess. Histopathology report revealed presence of chronic granulomatous inflammation with necrosis and numerous septate hyphae. A fungus culture was run which confirmed presence of heavy colonies of Aspergillus Flavus. Post-operatively the patient was kept on Voricoazole and anti-inflammatory medications. Conclusion: Fungal infections of the central nervous system are almost always a clinical surprise, and have subtle presentation. Any suspected lesion once removed should be sent for biopsy to rule out the presence of any fungal infection.

Dose-dependent enhancement of motion direction discrimination with transcranial magnetic stimulation of visual cortex

Despite the widespread use of transcranial magnetic stimulation (TMS) in research and clinical care, the underlying mechanisms-of-actions that mediate modulatory effects remain poorly understood. To fill this gap, we studied dose–response functions of TMS for modulation of visual processing. Our approach combined electroencephalography (EEG) with application of single pulse TMS to visual cortex as participants performed a motion perception task. During participants’ first visit, motion coherence thresholds, 64-channel visual evoked potentials (VEPs), and TMS resting motor thresholds (RMT) were measured. In second and third visits, single pulse TMS was delivered 30 ms before the onset of motion or at the onset latency of the N2 VEP component derived from the first session. TMS was delivered at 0%, 80%, 100%, or 120% of RMT over the site of N2 peak activity, or at 120% over vertex. Behavioral results demonstrated a significant main effect of TMS timing on accuracy, with better performance when TMS was applied at N2-Onset timing versus Pre-Onset, as well as a significant interaction, indicating that 80% intensity produced higher accuracy than other conditions. TMS effects on VEPs showed reduced amplitudes in the 80% Pre-Onset condition, an increase for the 120% N2-Onset condition, and monotonic amplitude scaling with stimulation intensity. The N2 component was not affected by TMS. These findings reveal dose–response relationships between intensity and timing of TMS on visual perception and electrophysiological brain activity, generally indicating greater facilitation at stimulation intensities below RMT.

Spastic paraparesis associated with advanced liver cirrhosis: a condition obscure in terms of treatment and prognosis

Hepatic myelopathy or spastic paraparesis of liver disease is an insidious onset condition with pure motor spastic paraparesis without sensory, bladder or bowel involvement in patients with chronic liver disease, in which the neurological dysfunction cannot be explained by other causes. It is a rare, relentlessly progressive and mostly irreversible neurological complication resulting from portosystemic shunts occurring spontaneously, created surgically or due to ‘functional shunting’. In some cases, no evidence of shunting is elicitable due to difficulty in locating the hidden collaterals. We report this rare case of a 33-year-old man with chronic liver disease presenting with spastic paraparesis after 11 months of resolution of an episode of hepatic encephalopathy.