The value of routine blood work-up in clinical stratification and prognosis of patients with amyotrophic lateral sclerosis.

BACKGROUND: There is an unmet need in amyotrophic lateral sclerosis (ALS) to provide specific biomarkers for the disease. Due to their easy availability, we aimed to investigate whether routine blood parameters provide useful clues for phenotypic classification and disease prognosis. METHODS: We analyzed a large inpatient cohort of 836 ALS patients who underwent deep phenotyping with evaluation of the clinical and neurophysiological burden of upper (UMN) and lower (LMN) motor neuron signs. Disability and progression rate were measured through the revised ALS Functional Rating Scale (ALSFRS-R) and its changes during time. Cox regression analysis was performed to assess survival associations. RESULTS: Creatinine significantly correlated with LMN damage (r = 0.38), active (r = 0.18) and chronic (r = 0.24) denervation and baseline ALSFRS-R (r = 0.33). Creatine kinase (CK), alanine (ALT) and aspartate (AST) transaminases correlated with active (r = 0.35, r = 0.27, r = 0.24) and chronic (r = 0.37, r = 0.20, r = 0.19) denervation, while albumin and C-reactive protein significantly correlated with LMN score (r = 0.20 and r = 0.17). Disease progression rate showed correlations with chloride (r = -0.19) and potassium levels (r = -0.16). After adjustment for known prognostic factors, total protein [HR 0.70 (95% CI 0.57-0.86)], creatinine [HR 0.86 (95% CI 0.81-0.92)], chloride [HR 0.95 (95% CI 0.92-0.99)], lactate dehydrogenase [HR 0.99 (95% CI 0.99-0.99)], and AST [HR 1.02 (95% CI 1.01-1.02)] were independently associated with survival. CONCLUSIONS: Creatinine is a reliable biomarker for ALS, associated with clinical features, disability and survival. Markers of nutrition/inflammation may offer additional prognostic information and partially correlate with clinical features. AST and chloride could further assist in predicting progression rate and survival.

Frontotemporal-spectrum disorders and functional independence in non-demented ALS patients.

BACKGROUND: The present study aimed at determining whether, net of motor confounders, neuropsychological features affect functional independence (FI) in activities of daily living (ADLs) in non-demented amyotrophic lateral sclerosis (ALS) patients. METHODS: N = 88 ALS patients without frontotemporal dementia were assessed for FI-Katz's Basic ADL Scale (BADL) and Lawton-Brody's Instrumental ADL Scale (IADL)-, cognition-Edinburgh Cognitive and Behavioural ALS Screen (ECAS)-and behaviour-Beaumont Behavioural Inventory and Dimensional Apathy Scale. The association between cognitive and behavioural measures and BADL/IADL scores was assessed by covarying for demographics, anxiety and depression levels, disease duration and motor confounders-i.e. ALS Functional Rating Scale-Revised (ALSFRS-R) scores, progression rate and both King's and Milano-Torino stages. RESULTS: Higher scores on the ECAS-Language were associated with higher IADL scores (p = 0.005), whilst higher apathetic features-as measured by the Dimensional Apathy Scale (DAS)-were inversely related to the BADL (p = 0.003). Whilst IADL scores were related to all ECAS-Language tasks, the DAS-Initiation was the only subscale associated with BADL scores. Patients with abnormal ECAS-Language (p = 0.023) and DAS (p = 0.008) scores were more functionally dependent than those without. DISCUSSION: Among non-motor features, language changes and apathetic features detrimentally affect FI in non-demented ALS patients.

Clinical usability of the Story-Based Empathy Task (SET) in non-demented ALS patients.

BACKGROUND: This study aimed at assessing the clinical usability of the Story-Based Empathy Task (SET) in non-demented amyotrophic lateral sclerosis (ALS) patients. METHODS: N = 106 non-demented ALS patients and N = 101 healthy controls (HCs) were administered the SET, which includes three subtests assessing Emotion Attribution (SET-EA), Intention Attribution (SET-IA) and causal inference (SET-CI) - the latter being a control task. Patients also underwent the Reading the Mind in the Eyes Test (RMET), the Edinburgh Cognitive and Behavioural ALS Screen (ECAS) and a thorough behavioural and motor-functional evaluation. The diagnostics of the SET-EA and -IA were tested against a defective performance on the RMET. The association between SET subtests and cognitive/behavioural outcomes was examined net of demographic and motor-functional confounders. Case-control discrimination was explored for each SET subtest. RESULTS: Demographically adjusted SET-EA and -IA scores accurately detected defective RMET performances at the optimal cutoffs of <3.04 (AUC = .84) and <3.61 (AUC = .88), respectively. By contrast, the SET-CI performed poorly in doing so (AUC = .58). The SET-EA converged with the RMET, as well as with ECAS-Executive and -Memory scores, whilst the SET-IA was unrelated to cognitive measures (including the RMET); the SET-CI was related to the ECAS-Language the ECAS-Executive. SET subscores were unrelated to behavioural outcomes. Only the SET-EA discriminated patients from HCs. CONCLUSIONS: The SET as a whole should not be addressed as a social-cognitive measure in this population. At variance, its subtest tapping on emotional processing - i.e., the SET-EA - is recommended for use as an estimate of social-cognitive abilities in non-demented ALS patients.

Newly Diagnosed Hepatic Encephalopathy Presenting as Non-convulsive Status Epilepticus: A Case Report and Literature Review.

Background: Hepatic encephalopathy is characterized by psychiatric and neurological abnormalities, including epileptic seizure and non-convulsive and convulsive status epilepticus. Conventional brain magnetic resonance imaging is useful in supporting diagnosis since it can reveal specific radiological findings. In the literature, there is no description of hepatic encephalopathy onset as non-convulsive status epilepticus; we provide the first report. Case Summary: We report a case of a 67-year-old woman, without history of cirrhosis, presenting altered mental state, normal brain computed tomography imaging, and electroencephalography suggestive of epileptic activity. We suspected non-convulsive status epilepticus, and we administered diazepam and levetiracetam with clinical improvement. Thus, we made a diagnosis of non-convulsive status epilepticus. A radiological study with brain magnetic resonance imaging showed bilateral hyperintensity on T1-weighted sequences of globus pallidus and hyperintensity of both corticospinal tracts on T2-weighted fluid-attenuated inversion recovery sequences. Blood tests revealed hyperammonemia, mild abnormality of liver function indices, and chronic Hepatitis B and D virus coinfection. Hepatic elastosonography suggested liver cirrhosis. The patient started antiviral therapy with entecavir and prevention of hepatic encephalopathy with rifaximin and lactulose; she was discharged with a normal mental state. Conclusions: Hepatic encephalopathy can present as an initial manifestation with non-convulsive status epilepticus. Electroencephalography is useful for differentiating non-convulsive status epilepticus from an episode of hepatic encephalopathy, and neuroimaging aids the diagnostic process.