Spinal-onset Patients Research Articles

Primary intramedullary spinal cord lymphoma misdiagnosed as longitudinally extensive transverse myelitis: a case report and literature review

BackgroundPrimary intramedullary spinal cord lymphoma (PISCL) is rare and easily misdiagnosed with the lack of typical clinical features and non-specific imaging manifestations.Case presentationA 49-year-old man was admitted to our hospital because of persistent limbs numbness, pinprick-like pain in the posterior neck and unsteady gaits. He has brisk tendon reflexes and positive Babinski’s sign. Magnetic resonance imaging (MRI) of the cervical spine showed an abnormal signal with aberrant reinforcement at medulla oblongata and the level of C1-C7. He was clinically diagnosed as longitudinally extensive transverse myelitis (antibody-negative). Steroid pulse therapy was administered and resulted in reduced symptoms. One month later, his situation was exacerbated compared to the onset. We launched a new cascade of steroid pulse therapy. But it did not improve his symptoms. Finally, the biopsy pathology confirmed PISCL. Chemotherapy, radiotherapy and zanubrutinib were administered and until now about 3 years into treatment the patient is still survival.ConclusionsBased on our case and literature review, we recommend that spinal onset patients react ineffectively to standard immunoglobulins or hormonal treatments or experience a relapse after a short time relief should take PISCL into consideration.

Impairment of oculomotor functions in patients with early to advanced amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) can result into an incomplete locked in state (iLIS), in which communication depends on eye tracking computer devices. Oculomotor function impairments in ALS have been reported, but there is little research, particularly with respect to patients in iLIS. In the present study, we compared reflexive and executive oculomotor function by means of an eye tracking test battery between three groups: advanced ALS patients in iLIS (n = 22), patients in early to middle ALS stages (n = 44) and healthy subjects (n = 32). Patients with ALS showed significant deteriorations in oculomotor functions, with stronger impairments in iLIS. More specifically, ALS patients produced visually guided prosaccades with longer latencies and more frequent hypometria compared to healthy subjects. Longest latencies were obtained in iLIS patients, with a stronger prolongation for vertical than for horizontal prosaccades. ALS patients made more antisaccade errors and generated antisaccades with longer latencies. Smooth pursuit was also impaired in ALS. In the earlier ALS stages, bulbar onset patients presented stronger antisaccade and smooth pursuit deficits than spinal onset patients. Our findings reveal a relevant deterioration of important oculomotor functions in ALS, which increases in iLIS. It includes impairments of reflexive eye movements to loss of executive inhibitory control, indicating a progressing pathological involvement of prefrontal, midbrain and brainstem areas. The assessment of oculomotor functions may therefore provide clinically relevant bio- and progression marker, particularly in advanced ALS.

Age of Onset and Length of Survival of Queensland Patients with Amyotrophic Lateral Sclerosis: Details of Subjects with Early Onset and Subjects with Long Survival

Introduction: The aims of the study were to document the characteristics of amyotrophic lateral sclerosis (ALS) patients in Queensland, to examine factors influencing age of onset, and survival, and to study those with early-onset (<45 years) disease and those with long (>5 years) survival. Methods: We studied subjects seen at the ALS Clinic at the Royal Brisbane and Women’s Hospital. We recorded sex, age of onset, region of onset, length of survival, presence of family history, type of disease, and evidence of cognitive involvement. We analysed the influence of these features on age of onset and survival. We analysed the features of patients with early onset of disease and patients with long survival. Results: There were 855 ALS patients (505 males) in the cohort. The age of onset was lower in males than females, in patients with a family history of ALS compared to those without, and in patients with spinal onset compared to bulbar onset. Early-onset disease was seen in 10% of patients, and had a greater proportion of males, spinal onset, and classical ALS phenotype compared to late-onset disease. Survival was shorter in females, in patients with bulbar onset, and in patients with classical ALS. Long survival was seen in 18% of patients. Patients with long survival had younger age of onset, greater proportion of males, spinal onset, and fewer patients with classical ALS. Conclusion: Our study confirms that ALS is more prevalent in males and that spinal onset is more common than bulbar onset. Males have earlier onset but longer survival. We found that overall, patients with classical ALS have worse survival than ALS variants, but some patients who were considered to have classical ALS had long survival. This study confirms the similarity of ALS in our region to ALS in other geographical regions.

Eye Movement Abnormalities in Amyotrophic Lateral Sclerosis.

It is generally believed that eye movements are completely spared in amyotrophic lateral sclerosis (ALS). Although a series of eye movement abnormalities has been recognized in recent years, the findings are highly controversial, and bulbar disabilities should be considered in relation to eye movement abnormalities. The present study aimed to determine whether eye movement abnormalities are present in ALS and, if so, to investigate their characteristics and their association with bulbar disability in ALS patients. A total of 60 patients and 30 controls were recruited and underwent the standardized evaluations of the oculomotor system using videonystagmography. Square-wave jerks (OR: 16.20, 95% CI: 3.50–74.95, p < 0.001) and abnormal cogwheeling during smooth pursuit (OR: 14.04, 95% CI: 3.00–65.75, p = 0.001) were more frequently observed in ALS patients than in the control subjects. In subgroup analyses, square-wave jerks (OR: 26.51, 95% CI: 2.83–248.05, p = 0.004) and abnormal cogwheeling during smooth pursuit (OR: 6.56, 95% CI: 1.19–36.16, p = 0.031) were found to be more common in ALS patients with bulbar involvement (n = 44) than in those without bulbar involvement (n = 16). There were no significant differences in the investigated eye movement parameters between bulbar-onset (n = 12) and spinal-onset patients (n = 48). ALS patients showed a range of eye movement abnormalities, affecting mainly the ocular fixation and smooth pursuit systems. Our pioneering study indicates that the region of involvement could better indicate the pathophysiological essence of the abnormalities than the type of onset pattern in ALS. Eye movement abnormalities may be potential clinical markers for objectively evaluating upper brainstem or supratentorial cerebral lesion neurodegeneration in ALS.

Comparative assessment of blood Metal/metalloid levels, clinical heterogeneity, and disease severity in amyotrophic lateral sclerosis patients

Amyotrophic lateral sclerosis is an unremitting neurodegenerative (ND) disease characterized by progressive and fatal loss of motor neuron function. While underlying mechanisms for ALS susceptibility are complex, current understanding suggests that interactions between age, genetic, and environmental factors may be the key. Environmental exposure to metal/metalloids has been implicated in various ND diseases including ALS, Alzheimer’s Disease (AD), and Parkinson’s Disease (PD). However, most of currently available population-based ALS studies in relation to metal exposure are based on individuals from European ancestry, while East Asian populations, especially cohorts from China, are less well-characterized. This study aims to examine the association between metal/metalloid levels and ALS onset by evaluating blood cadmium (Cd), lead (Pb), Cu, Zn, calcium (Ca), magnesium (Mg), and iron (Fe) levels in controls and sporadic ALS patients from North Western China. We report that Cu and Fe levels are found at higher levels in ALS patients compared to the controls. Spinal and bulbar onset patients show significant difference in Ca levels. Moreover, Cd, Pb, Cu, and Ca levels are positively correlated with high disease severity. Results from this study may provide new insights for understanding not only the role of metal/metalloids in ALS susceptibility, but also progression and forms of onset.

Correlations between measures of ALS respiratory function: is there an alternative to FVC?

Background: An ongoing longitudinal study in six European sites includes a 3-monthly assessment of forced vital capacity (FVC), slow vital capacity (SVC), peak cough flow (PCF), and Sniff nasal inspiratory pressure (SNIP). The aim of this interim analysis was to assess the potential for SNIP to be a surrogate for aerosol generating procedures given COVID-19 related restrictions. Methods: This was a prospective observational study. Patients attending six study sites with King’s Stage 2 or 3 ALS completed baseline FVC/SVC/SNIP/PCF and repeated assessments 3 monthly. Data were collected from March 2018 to March 2020, after which a COVID-19 related study suspension was imposed. Correlations between the measures were calculated. A Bayesian multiple outcomes random-effects model was constructed to investigate rates of decline across measures. Results: In total, 270 cases and 828 assessments were included (Mean age 65.2 ± 15.4 years; 32.6% Female; 60% Kings stage 2; 81.1% spinal onset). FVC and SVC were the most closely correlated outcomes (0.95). SNIP showed the least correlation with other metrics 0.53 (FVC), 0.54 (SVC), 0.60 (PCF). All four measures significantly declined over time. SNIP in the bulbar onset group showed the fastest rate of decline. Discussion: SNIP was not well correlated with FVC and SVC, probably because it examines a different aspect of respiratory function. Respiratory measures declined over time, but differentially according to the site of onset. SNIP is not a surrogate for FVC and SVC, but is a complementary measure, declining linearly and differentiating spinal and bulbar onset patients.

Prevalence and Factors Related to Pathological Laughter and Crying in Patients With Amyotrophic Lateral Sclerosis.

Objective: This study aimed to explore the prevalence and clinical correlates of pathological laughter and crying (PLC) in patients with amyotrophic lateral sclerosis (ALS).Methods: A total of 1,031 ALS patients were enrolled between August 2012 and August 2019. The PLC was recorded by a face-to-face interview. Other characteristics of patients, including depression, anxiety, cognition, and behavior function, were also evaluated. The potential associated factors of PLC were explored using forward binary regression analysis. Survival was analyzed in groups using propensity score matching (PSM) and Cox proportional hazards models.Results: The prevalence of PLC was 11.4% in all patients at baseline. Bulbar-onset and female patients had higher prevalence of PLC. The multivariate regression analysis indicated that PLC in ALS was associated with bulbar onset (p < 0.001), late disease stage (p < 0.001), and higher score in the Hamilton Depression Rating Scale (HDRS) (p = 0.012). The higher score of HDRS was significantly and independently associated with PLC occurrence in bulbar-onset patients (p = 0.032). The late disease stage was related to PLC occurrence in spinal-onset patients (p < 0.001). After comparison with matched pairs by using PSM, PLC at baseline had no impact on survival.Conclusion: PLC was not uncommon in ALS, especially in bulbar-onset and female patients. We highlighted that the emotional state other than cognitive function had possible relationship with PLC in ALS.

Clinical and epidemiological features of amyotrophic lateral sclerosis in eastern Turkey

Aim: The number of studies on the epidemiological and clinical data of amyotrophic lateral sclerosis (ALS) patients in Turkey is quite low and the studies on this subject reflect the data of western regions of Turkey. In this study, we aimed to present the demographic, clinical and mortality features of ALS patients diagnosed in the last 10 years in a large reference hospital in the Eastern Anatolia region of Turkey.&#x0D; Material and Method: 42 ALS patients diagnosed between January 2011 and January 2021 in ………., Faculty of Medicine, Department of Neurology were included in the study. The data of the patients were obtained by retrospectively scanning the patient electronic files registered in the database of our hospital. The age, gender, examination findings, clinical course, treatments they received and the cause of death of the patients were recorded.&#x0D; Results:26 of ALS patients were men and 16 were women. The mean age of onset was 53.4 ± 12.3 and the mean diagnostic delay was 13.6 ± 6.9 months. 64.2% of the patients had onset in the spinal region, and 35.7% in the bulbar region. Weakness/atrophy of the upper extremity muscles and swallowing difficulty were the most common onset symptoms. All ALS patients were using riluzole. 11 ALS patients died. The mean time between diagnosis and death in patients who died was 27.2 ± 18.6 months. The most common causes of death in ALS patients were pneumonia and sepsis.&#x0D; Conclusion: Age of onset of ALS was low in our patients. The number of patients in the clinically definite ALS group was the highest. Weakness/atrophy of the upper extremity muscles and swallowing difficulty were the most common onset symptoms. Approximately 2/3 of the patients had spinal, and 1/3 bulbar region onset. There was no significant difference between spinal and bulbar onset patients in terms of gender, age of disease onset, mortality, and life expectancy of patients with death. The rate of using riluzole was high. The most common causes of death in ALS patients were pneumonia and sepsis.

Swallowing Safety and Efficiency Impairment Profiles in Individuals with Amyotrophic Lateral Sclerosis.

Dysphagia is common in individuals with amyotrophic lateral sclerosis (ALS) and associated with reductions in quality of life and health-related outcomes. Despite the high prevalence of dysphagia in ALS, functional impairment profiles of swallowing safety and efficiency have not been comprehensively examined. We therefore aimed to determine the relative prevalence of unsafe and inefficient swallowing in a large cohort of individuals with ALS. We further sought to examine the impact of global and bulbar disease progression (Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised "ALSFRS-R" total and bulbar scores, respectively), disease duration, and onset type on swallowing impairment profiles.One hundred individuals with ALS completed a standardized videofluoroscopic swallowing examinationTwo independent and blinded raters performed validated ratings of safety (Penetration-Aspiration Scale, PAS) and efficiency (Analysis of Swallowing Physiology: Events, Kinematics, and Timing, ASPEKT % residue). Binary classifications of safety (unsafe: PAS ≥ 3), efficiency (inefficient: total residue ≥ 3% of C2-42) and global swallowing status were derived. The ALSFRS-R was completed to derive ALSFRS-R total and bulbar subscale scores.Demographic data (disease duration and onset type) for each participant was also recorded.Descriptives, 2 × 2 contingency tables with Fishers exact test, and independent samples t-tests were performed (α = 0.05). Prevalence of unsafe and inefficient swallowing was 48% and 73%, respectively. Global swallowing profiles were, in rank order: unsafe and inefficient (39%), inefficient but safe (34%), safe and efficient (18%), and unsafe but efficient (9%). There were no differences in global disease progression or disease duration across swallowing impairment profiles. ALSFRS-R bulbar subscale scores were significantly lower in unsafe versus safe swallowers, p<0.05. Spinal onset patients had a greater proportion of safe swallowers as compared to bulbar onset patients (p=0.000, Fisher's exacttest). Both spinal and bulbar onset patients demonstrated a higher prevalence of inefficient swallowers as compared to efficient swallowers (p=0.04, Fisher's exact test).Dysphagia was prevalent in this group of individuals with ALS. Approximately half demonstrated safety impairments and two-thirds had impairments in swallowing efficiency. Inefficient swallowing was approximately four times more likely to be the initial functional impairment in patients with one pathophysiologic functional impairment. A longitudinal study is needed to examine the temporal evolution of dysphagia in ALS.

The Characteristics of Cognitive Impairment in ALS Patients Depend on the Lateralization of Motor Damage.

(1) Background: Cognitive features of patients with amyotrophic lateral sclerosis (ALS) have never been specifically analyzed according to the lateralization of motor impairment. In the present study we investigated the cognitive performances of ALS patients to describe the relationship between motor and cognitive dysfunction, according to site and side of disease onset. (2) Methods: Six-hundred and nine ALS patients underwent a comprehensive neuropsychological evaluation at diagnosis in Turin ALS Centre Tests included—mini-mental state examination (MMSE), frontal assessment battery (FAB), trail-making test A/B (TMT A-B), digit span forward and backward (digit span FW/digit span BW), letter fluency test (FAS), category fluency test (CAT), Rey auditory verbal learning test (RAVLT), Babcock story recall test (BSRT), Rey-Osterrieth complex figure test (ROCFT), Wisconsin card sorting test (WCST), Raven’s coloured progressive matrices (CPM47). Cognitive performances of patients, grouped by side and site of onset, were statistically compared using z-scores, as appropriate. (3) Results: Bulbar patients and bilateral spinal onset patients (Sbil) were generally characterized by lower cognitive performances in most neuropsychological tests, when compared to patients with lateralized onset (right-side spinal onset, Sri and left-side spinal onset, Sle). Digit span backward and visual memory task (ROCFT) median z-scores were significantly higher, reflecting a better cognitive performance, in Sri patients when compared to bulbar/Sbil patients, while verbal memory tasks (RAVLT and BRST) resulted in significantly higher scores in Sle patients. Our results are in keeping with hemispheric functional lateralization of language and visuospatial abilities. (4) Conclusions: In ALS patients, as in other neurodegenerative diseases, we found a direct relationship between lateralized motor and cognitive features.

CSF neurotoxic metals/metalloids levels in amyotrophic lateral sclerosis patients: comparison between bulbar and spinal onset

IntroductionAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder of the central nervous system (CNS) that causes progressive and irreversible damage in motor neurons. Different causal hypotheses include genetic, viral, traumatic and environmental mechanisms, such as exposure to heavy metals. The aim of this study was to compare metal/metalloid levels in cerebro-spinal fluid of ALS subtypes (spinal vs bulbar clinical onset). Material and methodsThis observational study consecutively screened all ALS patients referring to the Neurology Clinic of the University of Catania (Italy). Inductively coupled plasma mass spectrometry (ICP-MS) was used to quantify magnesium (Mg), cuprum (Cu), selenium (Se), iron (Fe), manganese (Mn), vanadium (V), zinc (Zn), alluminium (Al), arsenic (As), cobalt (Co), nickel (Ni), mercury (Hg), lead (Pb), cadmium (Cd) and palladium (Pd) levels. ResultsThirty-seven patients were enrolled (62.2% females), median age of 65 years (IQR: 59–71 years). Thirty-one (83.8%) patients had a spinal onset and 6 (16.2%) a bulbar onset. Se and As levels were higher compared to the reference values (RV) both in spinal and bulbar onset, while Cu was higher than RV only in bulbar onset. Moreover, Cu (129.8 μg/L vs 29.8 μg/L), Fe (54.5 μg/L vs 33.3 μg/L), Mn (3.4 μg/L vs 1.8 μg/L), Zn (46.1 μg/L vs 35.7 μg/L), Al (12.2 μg/L vs 6.7 μg/L), Ni (2.80 μg/L vs 1.40 μg/L), and Pb (0.60 μg/L vs 0.30 μg/L) levels were higher in bulbar than in spinal onset, conversely As was slightly higher in spinal than in bulbar onset (1.40 μg/L vs 1.10 μg/L). Overall, Cu (129 μg/L vs 31 μg/L), Fe (92.2 μg/L vs 32.9 μg/L), Mn (3.35 μg/L vs 1.80 μg/L), Zn (56.5 μg/L vs 35.2 μg/L), Al (14.45 μg/L vs 6.70 μg/L), and Cd (0.40 μg/L vs 0.08 μg/L) levels were higher in patients with disease duration less than 19 months. ConclusionOur results supported the hypothesis that metals/metalloids with neurotoxic effects could be involved in the etiology of ALS, showing higher levels of Cu, Se and As. Relevant differences in Cu and Mn levels were found between bulbar and spinal onset patients.

Prognostic value of weight loss in patients with amyotrophic lateral sclerosis: a population-based study

ObjectiveTo determine the prevalence and prognostic value of weight loss (WL) prior to diagnosis in patients with amyotrophic lateral sclerosis (ALS).MethodsWe enrolled patients diagnosed with ALS between 2010 and 2018...

The C9orf72 expansion is associated with accelerated respiratory function decline in a large Amyotrophic Lateral Sclerosis cohort

Introduction: The C9orf72 hexanucleotide repeat expansion is causal in amyotrophic lateral sclerosis (ALS) and has a negative effect on prognosis. The C9orf72 repeat expansion has been associated with an accelerated deterioration of respiratory function and survival in a cohort of 372 Portuguese patients. Methods: Cases presenting to the Irish ALS clinic with both longitudinal occluded sniff nasal inspiratory pressure (SNIP) and C9orf72 testing were including in the study. Clinical variables and survival characteristics of these patients were collected. Joint longitudinal and time to event models were constructed to explore the longitudinal characteristics of the cohort by C9orf72 status. Results: In total, 630 cases were included, of which 58 (9.2%) carried the C9orf72 repeat expansion. Plots of the longitudinal trend after joint modelling revealed that those carrying the expansion had worse respiratory function throughout the course of their disease than those without. The ALS Functional Rating Scale-revised (ALSFRS-R) respiratory sub-score did not distinguish C9orf72 normal from expanded cases. Furthermore, modelling by site of onset and gender sub-groups revealed that this difference was greatest in male spinal onset cases. Joint models further indicated that occluded SNIP values were of prognostic importance. Conclusions: Our results confirm findings from Portugal that the C9orf72 repeat expansion is associated with accelerated respiratory function decline. Analysis via joint models indicate that respiratory function is of prognostic importance and may explain previous observations of poorer prognosis in male spinal onset patients carrying the C9orf72 expansion.

The C9orf72 expansion is associated with accelerated respiratory function decline in a large Amyotrophic Lateral Sclerosis cohort.

Introduction: The C9orf72 hexanucleotide repeat expansion is causal in amyotrophic lateral sclerosis (ALS) and has a negative effect on prognosis. The C9orf72 repeat expansion has been associated with an accelerated deterioration of respiratory function and survival in a cohort of 372 Portuguese patients. Methods: Cases presenting to the Irish ALS clinic with both longitudinal occluded sniff nasal inspiratory pressure (SNIP) and C9orf72 testing were including in the study. Clinical variables and survival characteristics of these patients were collected. Joint longitudinal and time to event models were constructed to explore the longitudinal characteristics of the cohort by C9orf72 status. Results: In total, 630 cases were included, of which 58 (9.2%) carried the C9orf72 repeat expansion. Plots of the longitudinal trend after joint modelling revealed that those carrying the expansion had worse respiratory function throughout the course of their disease than those without. The ALS Functional Rating Scale-revised (ALSFRS-R) respiratory sub-score did not distinguish C9orf72 normal from expanded cases. Furthermore, modelling by site of onset and gender sub-groups revealed that this difference was greatest in male spinal onset cases. Joint models further indicated that occluded SNIP values were of prognostic importance. Conclusions: Our results confirm findings from Portugal that the C9orf72 repeat expansion is associated with accelerated respiratory function decline. Analysis via joint models indicate that respiratory function is of prognostic importance and may explain previous observations of poorer prognosis in male spinal onset patients carrying the C9orf72 expansion.

Early weight loss in amyotrophic lateral sclerosis: outcome relevance and clinical correlates in a population-based cohort

ObjectivesTo assess the role of body mass index (BMI) and of the rate of weight loss as prognostic factors in amyotrophic lateral sclerosis (ALS) and to explore the clinical correlates...

Testing the diagnostic accuracy of [18F]FDG-PET in discriminating spinal- and bulbar-onset amyotrophic lateral sclerosis

The role for [18F]FDG-PET in supporting amyotrophic lateral sclerosis (ALS) diagnosis is not fully established. In this study, we aim at evaluating [18F]FDG-PET hypo- and hyper-metabolism patterns in spinal- and bulbar-onset ALS cases, at the single-subject level, testing the diagnostic value in discriminating the two conditions, and the correlations with core clinical symptoms severity. We included 95 probable-ALS patients with [18F]FDG-PET scan and clinical follow-up. [18F]FDG-PET images were analyzed with an optimized voxel-based-SPM method. The resulting single-subject SPM-t maps were used to: (a) assess brain regional hypo- and hyper-metabolism; (b) evaluate the accuracy of regional hypo- and hyper metabolism in discriminating spinal vs. bulbar-onset ALS; (c) perform correlation analysis with motor symptoms severity, as measured by ALS-FRS-R. Primary motor cortex showed the most frequent hypo-metabolism in both spinal-onset (∼57%) and bulbar-onset (∼64%) ALS; hyper-metabolism was prevalent in the cerebellum in both spinal-onset (∼56.5%) and bulbar-onset (∼55.7%) ALS, and in the occipital cortex in bulbar-onset (∼62.5%) ALS. Regional hypo-and hyper-metabolism yielded a very low accuracy (AUC<0.63) in discriminating spinal- vs. bulbar-onset ALS, as obtained from single-subject SPM-t-maps. Severity of motor symptoms correlated with hypo-metabolism in sensorimotor cortex in spinal-onset ALS, and with cerebellar hyper-metabolism in bulbar-onset ALS. The high variability in regional hypo- and hyper-metabolism patterns, likely reflecting the heterogeneous pathology and clinical phenotypes, limits the diagnostic potential of [18F]FDG-PET in discriminating spinal and bulbar onset patients.

Interplay between spinal cord and cerebral cortex metabolism in amyotrophic lateral sclerosis.

We recently reported the potential of Hough transform in delineating spinal cord metabolism by 18F-fluorodeoxyglucose PET/CT scanning in amyotrophic lateral sclerosis. The present study aimed to verify the relationship between spinal cord and brain metabolism in 44 prospectively recruited patients affected by amyotrophic lateral sclerosis submitted to 18F-fluorodeoxyglucose brain and whole-body PET/CT. Patients were studied to highlight the presence of brain hypo- or hypermetabolism with respect to healthy controls, and multiple regression analysis was performed to evaluate the correlation between spinal cord and brain metabolism. Our results confirmed higher 18F-fluorodeoxyglucose uptake in both cervical and dorsal spinal cord in patients with amyotrophic lateral sclerosis with respect to controls. This finding was paralleled by the opposite pattern in the brain cortex that showed a generalized reduction in tracer uptake. This hypometabolism was particularly evident in wide regions of the frontal-dorsolateral cortex while it did not involve the midbrain. Bulbar and spinal disease onset was associated with similar degree of metabolic activation in the spinal cord. However, among spinal onset patients, upper limb presentation was associated with a more pronounced metabolic activation of cervical segment. Obtained data suggest a differential neuro-pathological state or temporal sequence in disease progression.

Sniff nasal inspiratory pressure (SNIP) in amyotrophic lateral sclerosis: Relevance of the methodology for respiratory function evaluation

ObjectivesWe investigated two different methodological approaches for determining nasal inspiratory pressure during a sniff (SNIP) in patients with Amyotrophic Lateral Sclerosis (ALS). Patients and MethodsWe included 37 ALS patients and 11 controls. SNIP was measured in the sitting position, performed in each nostril with (SNIPocclud) and without (SNIPopen) closing the contralateral nostril. The best of 3 consistent results was considered for analyses. Patients were also assessed with MIP and the revised functional ALS rating scale (ALSFRS-R). Mann-Whitney U test, Wilcoxon test and Spearman's rank correlation coefficient with Bonferroni correction were applied. Coefficient of variation (CV) was calculated. ResultsSNIP was significantly lower in patients than controls, either for SNIPopen (p = 0.011) or SNIPocclud (p = 0.002). SNIPopen values were significantly lower both in ALS patients and controls than SNIPocclud (p < 0.001 and p = 0.007, respectively). SNIPopen CV was 8.14% and 8.51%, while SNIPocclud CV was 4.98% and 6.37%, respectively for controls and patients. SNIPopen and SNIPocclud were strongly correlated in both groups (r = 0.761 for controls; r = 0.768 for patients). In ALS, both methods were moderately correlated with MIP (respectively r = 0.525, p = 0.006 and r = 0.685, p < 0.001) and the respiratory subscore of ALSFRS-R (respectively r = 0.525, p = 0.001 and r = 0.64, p < 0.001). Although bulbar and spinal onset patients presented no differences for SNIPopen (p = 0.157), significant differences were found for SNIPocclud (p = 0.018). ConclusionSNIPocclud should be considered when evaluating ALS patients as its values present lower variability and favor longer follow-up.

Health Status Perspectives in Amyotrophic Lateral Sclerosis

Background/Aims: The global perception of the health status (HS) of amyotrophic lateral sclerosis (ALS) patients before the initial diagnosis has not been addressed previously. Methods: We recorded the following at the first visit, before diagnostic information: (1) visual analog scale (VAS) of the EQ-5D; (2) the revised ALS functional rating scale (ALSFRS- R), bulbar (ALSFRSb), upper limb (ALSFRSul), lower limb (ALSFRSll), and respiratory (RofALSFRS-R) subscores; and (3) forced and slow vital capacities. Correlations were tested by the Pearson correlation test. Variables were compared between groups defined by the VAS median value. p < 0.05 was considered significant. Results: Of the 156 patients included in the study (91 spinal-onset, 49 bulbar-onset, 16 axial/respiratory-onset; 95 men; mean onset age 63.9 ± 13 years; mean disease duration 18.4 ± 26.5 months), HS VAS was significantly lower in spinal-onset patients (p = 0.047), and particularly in spinal-onset women (p = 0.027). Disease duration had no influence. HS VAS was moderately correlated with ALSFRS, ALSFRSul and ALSFRSll (0.4 < r < 0.5, p < 0.01), weakly correlated with RofALSFRS-R in the whole population (r = 0.171, p < 0.05), and not correlated with ALSFRSb or the respiratory tests. ALSFRSb was similar between groups defined by the HS VAS median value, but the other scores were significantly lower for poorer HS values. Conclusion: HS before diagnosis is mostly dependent on the perception of upper and lower limb function. A tool tailored to evaluate HS in bulbar-onset patients should be developed.

Dysphagia in Amyotrophic Lateral Sclerosis: Impact on Patient Behavior, Diet Adaptation, and Riluzole Management.

This retrospective study aimed to investigate the clinical features associated with deteriorated swallow in amyotrophic lateral sclerosis (ALS) patients with spinal and bulbar onset, describe the modification of diet and liquid intake, and assess the impact of dysphagia on the use of riluzole. One hundred forty-five patients were observed periodically every 3–6 months. They underwent routinely fiberoptic endoscopic evaluation of swallowing (FEES) and spirometry; dysphagia severity was classified according to the Penetration Aspiration Scale and the Pooling score (P-score) integrated with other parameters such as sensation, collaboration, and age (P-SCA score). During a mean follow-up period of about 2 years, the percentage of ALS patients suffering from dysphagia increased to 85 (rising from 35 to 73% in patients with spinal onset and from 95 to 98% in those with bulbar onset). Also, 8% of patients with dysphagia by FEES did not perceive the disorder. The frequency of normal and semi-solid diets decreased over time, while that of pureed diets and percutaneous endoscopic gastrostomy (PEG) prescription increased. Forty-four percent of dysphagic patients refused thickeners or PEG. A significant difference was observed in the mortality rate between patients untreated with riluzole and patients treated with riluzole oral suspension (p < 0.05). Disease duration mainly impacted on the frequency of dysphagia in spinal onset patients, appearing very early in those with bulbar onset. Riluzole oral suspension would allow the safe administration in dysphagic ALS patients to avoid tablet crushing and consequent dispersion in food, common practices that are inconsistent with the safe and effective use of the drug.