Cross‐disease comparison of amyotrophic lateral sclerosis and spinal muscular atrophy reveals conservation of selective vulnerability but differential neuromuscular junction pathology

Neuromuscular junctions are primary pathological targets in the lethal motor neuron diseases spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS). Synaptic pathology and denervation of target muscle fibers has been reported prior to the appearance of clinical symptoms in mouse models of both diseases, suggesting that neuromuscular junctions are highly vulnerable from the very early stages, and are a key target for therapeutic intervention. Here we examined neuromuscular pathology longitudinally in three clinically relevant muscle groups in mouse models of ALS and SMA in order to assess their relative vulnerabilities. We show for the first time that neuromuscular junctions of the extraocular muscles (responsible for the control of eye movement) were resistant to degeneration in endstage SMA mice, as well as in late symptomatic ALS mice. Tongue muscle neuromuscular junctions were also spared in both animal models. Conversely, neuromuscular junctions of the lumbrical muscles of the hind‐paw were vulnerable in both SMA and ALS, with a loss of neuronal innervation and shrinkage of motor endplates in both diseases. Thus, the pattern of selective vulnerability was conserved across these two models of motor neuron disease. However, the first evidence of neuromuscular pathology occurred at different timepoints of disease progression, with much earlier evidence of presynaptic involvement in ALS, progressing to changes on the postsynaptic side. Conversely, in SMA changes appeared concomitantly at the neuromuscular junction, suggesting that mechanisms of neuromuscular disruption are distinct in these diseases. J. Comp. Neurol. 524:1424–1442, 2016. © 2015 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.     

Migraine with aura after intracranial endovascular procedures

OBJECTIVE: To describe three cases of migraine (two with aura) after an intracranial endovascular procedure. Method.-Retrospective. RESULTS: One patient had an attack of migraine with prolonged aura after embolization of a dural arteriovenous fistula. Another patient had an attack of migraine with aura (and hemiparesis) after a diagnostic angiogram. The third patient already suffered from migraine with aura and had a migraine attack after embolization of an occipital arteriovenous malformation. A quadrantanopia persisted in this patient. Outcome of the other two patients was good. CONCLUSION: Intracranial endovascular procedures can induce migraine with aura. We could not identify the underlying pathophysiological mechanism, but mechanical, chemical, immunological, or hemodynamic factors could be involved.     

A comparison of hexaminolevulinate fluorescence cystoscopy and white light cystoscopy for the detection of carcinoma in situ in patients with bladder cancer: a phase III, multicenter study

PURPOSE: We compared hexaminolevulinate (Hexvix) fluorescence cystoscopy with white light cystoscopy for detecting carcinoma in situ. MATERIALS AND METHODS: In this multicenter study 298 patients with known or suspected bladder cancer underwent bladder instillation with 50 ml 8 mM hexaminolevulinate for 1 hour. Cystoscopy was then performed, first using standard white light and then hexaminolevulinate fluorescence cystoscopy. Lesions or suspicious areas identified under the 2 illumination conditions were mapped and biopsied for histological examination. In addition, 1 directed biopsy was obtained from an area appearing to be normal. RESULTS: Of 196 evaluable patients 29.6% (58 of 196) had carcinoma in situ, including 18 with carcinoma in situ alone, and 35 with carcinoma in situ and concomitant papillary disease, which was only detected on random biopsy in 5. Of the 18 patients with no concomitant papillary disease carcinoma in situ was detected only by hexaminolevulinate fluorescence in 4 and only by white light in 4. In the group with concomitant papillary disease carcinoma in situ was found only by hexaminolevulinate fluorescence in 5 patients and only by white light in 3. The proportion of patients in whom 1 or more carcinoma in situ lesions were found only by hexaminolevulinate cystoscopy was greater than the hypothesized 5% (p=0.0022). Overall more carcinoma in situ lesions were found by hexaminolevulinate than by white light cystoscopy in 22 of 58 patients (41.5%), while the converse occurred in 8 of 58 (15.1%). Biopsy results confirmed cystoscopy findings. Of a total of 113 carcinoma in situ lesions in 58 patients 104 (92%) were detected by hexaminolevulinate cystoscopy and 77 (68%) were detected by white light cystoscopy, while 5 were detected only on directed visually normal mucosal biopsy. Hexaminolevulinate instillation was well tolerated with no local or systemic side effects. CONCLUSIONS: In patients with bladder cancer hexaminolevulinate fluorescence cystoscopy with blue light can diagnose carcinoma in situ that may be missed with white light cystoscopy. Hexaminolevulinate fluorescence cystoscopy can be used in conjunction with white light cystoscopy to aid in the diagnosis of this form of bladder cancer.     

Dorsal lunate tilt (DISI configuration): sign of scaphoid fracture displacement

Excessive dorsiflexion (dorsal tilting) of the lunate on a lateral wrist radiograph can be an important sign of carpal injury. Lunate dorsiflexion is a well-recognized sign of an intercarpal ligamentous injury pattern known as dorsal intercalated segment instability (DISI). It is less well recognized that excessive dorsal tilting of the lunate (DISI configuration) can also be produced by displacement of a scaphoid waist fracture. Since the management and prognosis of displaced scaphoid fractures may be quite different from those for nondisplaced fractures, radiologists can make an important contribution by recognizing dorsal tilting of the lunate and appreciating that it may be an important, indirect sign of scaphoid fracture displacement, which may not be directly visualized with standard wrist radiography. In this setting, computed tomography or complex motion tomography may be helpful for further evaluation of the scaphoid fracture.     

Autosomal dominant adult neuronal ceroid lipofuscinosis: parkinsonism due to both striatal and nigral dysfunction.

We describe a family with adult neuronal ceroid lipofuscinosis, with apparent autosomal dominant inheritance, observed in six affected individuals in three generations. Disease onset was usually in the fifth decade, but was earlier in the youngest generation. Early symptoms consisted of myoclonus in face and arms, epilepsy, auditory symptoms, cognitive decline, or depression. Parkinsonism occurred a few years after disease onset, with stooped posture, shuffling gait, bradykinesia, and mask face. Four subjects deteriorated to a state of severe handicap, with severe dementia, contractures, dysphagia, and dysarthria. Leg weakness evolved to flaccid paraparesis in two patients. Diagnosis was confirmed by brain biopsy in one patient and full autopsy in two patients. Abundant intraneuronal storage of autofluorescent material was found throughout the brain. Electron microscopy showed granular osmiophilic deposits and scarce fingerprint profiles. Striking loss of neurons in the substantia nigra pars compacta and reticulata was found. (123)I-IBZM Single photon emission computed tomography in two patients showed loss of postsynaptic D2 receptor binding in the striatum. We conclude that parkinsonism in ANCL is likely to be caused by both presynaptic nigral cell loss and postsynaptic striatal degeneration.     

Obesity: Risk Factor for Increased Resource Utilization at Bidirectional Glenn

Background

Underweight infants with single‐ventricle cardiac physiology have been shown to have increased morbidity, mortality, and resource utilization. The purpose of this study was to determine whether patients who were overweight, as defined by weight‐for‐length z score >90th percentile, were similarly at risk for increased resource utilization, as defined by mechanical ventilation hours (VHs) and intensive care unit length of stay (ICU LOS).

Methods

We evaluated resource utilization for 109 patients from our institution who underwent bidirectional Glenn surgery from January 2010 to June 2015 and met prespecified inclusion criteria. Patients were divided into 3 groups: underweight (z score, <5th percentile), normal weight (z score, 5th–90th percentile), and overweight (z score, >90th percentile).

Results

ICU LOS was longer in the overweight group (median, 18.5 days) when compared with the under‐ and normal‐weight groups (median LOS, 11 and 9 days, respectively) but did not reach statistical significance. VHs were also increased in the overweight group (median, 72 hours) when compared with the underweight (median, 27 hours) and normal weight (median, 25 hours) groups. This increase in VHs was statistically significant (P = .03).

Conclusions

This study suggests that patients with single‐ventricle physiology who are overweight at the time of their bidirectional Glenn surgery may be at risk for increased resource utilization as compared with those who meet or fail to meet their caloric recommendations. These findings represent an underappreciated risk factor in this already‐vulnerable patient population, providing potential opportunity for intervention and improved outcomes.     

Dilation of the aortic root in children infected with human immunodeficiency virus type 1: The Prospective P2C2 HIV Multicenter Study

BACKGROUND: Vascular lesions have become more evident in human immunodeficiency virus type 1 (HIV)-infected patients as the result of earlier diagnosis, improved treatment, and longer survival. Aortic root dilation in HIV-infected children has not previously been described. This study was undertaken to determine the prevalence of aortic root dilation in HIV-infected children and to evaluate some of the potential pathogenic mechanisms. METHODS: Aortic root measurements were incorporated into the routine echocardiographic surveillance of 280 children of HIV-infected women: an older cohort of 86 HIV-infected children and a neonatal cohort of 50 HIV-infected and 144 HIV-uninfected children. RESULTS: By repeated-measures analyses, mean aortic root measurements were significantly increased in HIV-infected children versus HIV-uninfected children (P values of < or =.04 and < or =.005 at 2 and 5 years of age, respectively, for aortic annulus diameter, sinuses of Valsalva, and sinotubular junction). Heart rate, systolic blood pressure, stroke volume, hemoglobin, and hematocrit were not significantly associated with aortic root size. Left ventricular dilation, increased serum HIV RNA levels, and lower CD4 cell count measurements were associated with aortic root dilation at baseline. CONCLUSIONS: Mild and nonprogressive aortic root dilation was seen in children with vertically transmitted HIV infection from 2 to 9 years of age. Aortic root size was not significantly associated with markers for stress-modulated growth; however, aortic root dilation was associated with left ventricular dilation, increased viral load, and lower CD4 cell count in HIV-infected children. As prolonged survival of HIV-infected patients becomes more prevalent, some patients may require long-term follow-up of aortic root size.     

Work ability of Dutch employees with rheumatoid arthritis

OBJECTIVES: To (i) examine the association between fatigue, psychosocial work characteristics (job control, support, participation in decision making, psychological job demands), and physical work requirements on the one hand and work ability of employees with rheumatoid arthritis (RA) on the other, and (ii) determine the advice that health care professionals give to employees with RA on how to maintain their work ability. METHODS: Data were gathered from 78 employees with early RA (response = 99%) by telephone interviews and self-report questionnaires. RESULTS: Fatigue, lack of autonomy, low coworker/supervisor support, low participation in decision making, and high physical work requirements (i.e. using manual force) predicted low work ability. High psychological job demands, however, did not predict low work ability. The rheumatologist, occupational physician, occupational therapist, physiotherapist, and psychologist gave advice on how to cope with RA at work to 36, 30, 27, 26, and 17% of the employees, respectively. Advice was directed mainly at factors intrinsic to the employee. Employees expressed a positive attitude towards this advice. CONCLUSIONS: Fatigue, lack of support, lack of autonomy, lack of participation in decision making, and using manual force at work (e.g. pushing and pulling) threaten the work ability of employees with RA. According to the employees with RA, involvement of health care professionals from different disciplines and the implementation of organizational and technical interventions would help them to tackle these threats.