8 research outputs found
Clinical and Radiological Markers of Extra-Motor Deficits in Amyotrophic Lateral Sclerosis
Amyotrophic lateral sclerosis (ALS) is now universally recognized as a complex multisystem disorder with considerable extra-motor involvement. The neuropsychological manifestations of frontotemporal, parietal, and basal ganglia involvement in ALS have important implications for compliance with assistive devices, survival, participation in clinical trials, caregiver burden, and the management of individual care needs. Recent advances in neuroimaging have been instrumental in characterizing the biological substrate of heterogeneous cognitive and behavioral deficits in ALS. In this review we discuss the clinical and radiological aspects of cognitive and behavioral impairment in ALS focusing on the recognition, assessment, and monitoring of these symptoms
The Clinical and Radiological Spectrum of Hippocampal Pathology in Amyotrophic Lateral Sclerosis
Hippocampal pathology in Amyotrophic Lateral Sclerosis (ALS) remains surprisingly under recognized despite compelling evidence from neuropsychology, neuroimaging and neuropathology studies. Hippocampal dysfunction contributes significantly to the clinical heterogeneity of ALS and requires structure-specific cognitive and neuroimaging tools for accurate in vivo evaluation. Recent imaging studies have generated unprecedented insights into the presymptomatic and longitudinal processes affecting this structure and have contributed to the characterisation of both focal and network-level changes. Emerging neuropsychology data suggest that memory deficits in ALS may be independent from executive dysfunction. In the era of precision medicine, where the development of individualized care strategies and patient stratification for clinical trials are key priorities, the comprehensive review of hippocampal dysfunction in ALS is particularly timely
Anti-Hu antibody seropositive neuropathy with large and small fiber involvement mimicking alcoholic neuropathy: a case report
Abstract Background Anti-Hu antibody neuropathy is considered a rare acquired peripheral neuropathy, but common among paraneoplastic syndromes. Typically, is described as subacute sensory neuronopathy and electrophysiological findings are usually suggestive of a sensory axonal neuropathy. Case presentation We report the case of a 67-year-old man referred to our clinic with a 4-month history of progressive pain and paresthesias of distal lower limbs. He had a 30-year history of alcohol abuse and smoking. Alcoholic neuropathy was considered the most likely diagnosis, considering his history and evaluation. The patient’s neurological examination revealed symmetric bilateral superficial and deep sensory loss in the lower extremities, reduced Achilles tendon reflexes and wide based gait. Electrophysiological testing was suggestive of axonal sensory-motor polyneuropathy and small fiber involvement. Even though alcohol consumption was discontinued, symptoms gradually worsened. Further testing was performed and the patient was found seropositive for anti-Hu antibody. Small-cell lung cancer was detected later, but patient passed away before treatment for cancer was administrated. Conclusions The aim of our paper is to report a case of a rare paraneoplastic syndrome that can cause progressive sensory-motor neuropathy with large and small fiber involvement, which should be rapidly differentially diagnosed from other neuropathies, so that the underlying cause can be identified and, potentially, treated
Corticosteroids for spontaneous intracranial hypotension: a case-report and critical review focusing on pathophysiology and treatment
Background Spontaneous intracranial hypotension (SIH) is characterized
by positional headache caused by low CSF pressure, without any major
traumatic event. Optimal treatment is still debated; epidural blood
patch (EBP) is usually used after unsuccessful conservative treatment
with variable efficacy and potentially severe complications. Although
steroids have been reported to be beneficial, their effectiveness is
still controversial, and more clinical evidence is needed. Case
presentation A 37-year-old woman was admitted to the neurology
department due to severe orthostatic headache with nausea over the last
5 days. No trauma history or spinal manipulation were mentioned. On
arrival, neurological examination, brain CT, and laboratory
investigation were normal. Intracranial hypotension was clinically
suspected, and lumbar puncture revealed low opening pressure. Brain MRI
demonstrated pachymeningeal gadolinium enhancement and distended and
rounded dural venous sinuses, while cervicothoracic spine MRI revealed
thoracic CSF leakage, leading to SIH diagnosis. The patient was treated
with high-dose intravenous methylprednisolone, with complete clinical
resolution within 24 h. Conclusions Our case, combined with literature
evidence, supports the high-dose intravenous corticosteroids as a
reasonable treatment option in selected cases, before trying EBP or
surgical repair. Randomized clinical trials are needed, in order to
optimize SIH patients' outcomes
The Clinical and Radiological Spectrum of Hippocampal Pathology in Amyotrophic Lateral Sclerosis
Hippocampal pathology in Amyotrophic Lateral Sclerosis (ALS) remains
surprisingly under recognized despite compelling evidence
fromneuropsychology, neuroimaging and neuropathology studies.
Hippocampal dysfunction contributes significantly to the clinical
heterogeneity of ALS and requires structure-specific cognitive and
neuroimaging tools for accurate in vivo evaluation. Recent imaging
studies have generated unprecedented insights into the presymptomatic
and longitudinal processes affecting this structure and have contributed
to the characterisation of both focal and network-level changes.
Emerging neuropsychology data suggest that memory deficits in ALS may be
independent from executive dysfunction. In the era of precision
medicine, where the development of individualized care strategies and
patient stratification for clinical trials are key priorities, the
comprehensive review of hippocampal dysfunction in ALS is particularly
timely
New molecular diagnostic trends and biomarkers for amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis (ALS) is a rare and fatal
neurodegenerative disorder. Two forms are recognized, familial (FALS)
that accounts for 5-10% of ALS cases, and sporadic (SALS) that accounts
for the rest. Early diagnosis of ALS is important because it improves
their therapeutic efficacy. Current diagnosis is based on clinical
assessment and requires approximately 12 months, leading to a
significant delay in drug administration. Therefore, new methods are
required for the earlier diagnosis of ALS. Screening for pathogenic
variants in known ALS-associated genes is already exploited as a
diagnostic tool in ALS but cannot be applied for population-based
screening. New circulating biomarkers (proteins or small molecules) are
needed for initial screening, whereas specific diagnostic methods can be
applied to confirm the presence of pathogenic variants in the selected
population subgroup. Lipids appear as promising biomarkers for
population-based screening and for monitoring disease progression.
Genetic analysis can also assist in the prediction of disease
progression by analyzing disease-modifying genes, for example, EPHA4 and
CHGB. Furthermore, molecular diagnosis will aid the stratification of
ALS patients for improved pharmacological approaches. Here, we discuss
current and novel diagnostic strategies and how they can be applied to
revolutionize the field of ALS molecular diagnosis
The association of theory of mind with language and visuospatial abilities in amyotrophic lateral sclerosis: a pilot study
International audienceObjective: Dysfunction of social cognition is well-recognized as one of amyotrophic lateral sclerosis (ALS) cognitive impairments. Previous studies have mostly associated social cognition subcomponents, including Theory of Mind (ToM), with executive dysfunction using highlydemanding tasks. In the present study, we investigate dysfunction of affective ToM in a sample of ALS patients without dementia and evaluate any possible associations both with executive and non-executive dysfunction. Methods: We included 42 ALS patients and 30 healthy controls (HC) and administered the Edinburgh Cognitive and Behavioural Amyotrophic Lateral Sclerosis Screen (ECAS). Affective ToM was examined based on the ECAS judgment of preference task; total score and type of errors ("favourite", "unclassified") were recorded for all participants. Results: A significant proportion of ALS patients (31%) were impaired on ToM task, scoring significantly lower compared to HC. Impairments in ToM task were more frequent (45%) in patients with cognitive impairment compared to those with intact cognition (15%). ALS patients showed significantly more errors on ToM task compared to HC. A significant association was found between ToM score and ECAS language and visuospatial abilities but not fluency, executive or memory function. Conclusion: Dysfunction of affective ToM appears prevalent in ALS patients without dementia, and associates with language and visuospatial abilities. These associations align with motor and extra-motor symptoms due to the degeneration across corresponding networks. Impaired ToM should be considered in clinical settings, since it might contribute to patients' social life, as well as the burden of their caregivers and relatives
Hippocampal Metabolic Alterations in Amyotrophic Lateral Sclerosis: A Magnetic Resonance Spectroscopy Study
Background: Magnetic resonance spectroscopy (MRS) in amyotrophic lateral sclerosis (ALS) has been overwhelmingly applied to motor regions to date and our understanding of frontotemporal metabolic signatures is relatively limited. The association between metabolic alterations and cognitive performance in also poorly characterised. Material and Methods: In a multimodal, prospective pilot study, the structural, metabolic, and diffusivity profile of the hippocampus was systematically evaluated in patients with ALS. Patients underwent careful clinical and neurocognitive assessments. All patients were non-demented and exhibited normal memory performance. 1H-MRS spectra of the right and left hippocampi were acquired at 3.0T to determine the concentration of a panel of metabolites. The imaging protocol also included high-resolution T1-weighted structural imaging for subsequent hippocampal grey matter (GM) analyses and diffusion tensor imaging (DTI) for the tractographic evaluation of the integrity of the hippocampal perforant pathway zone (PPZ). Results: ALS patients exhibited higher hippocampal tNAA, tNAA/tCr and tCho bilaterally, despite the absence of volumetric and PPZ diffusivity differences between the two groups. Furthermore, superior memory performance was associated with higher hippocampal tNAA/tCr bilaterally. Both longer symptom duration and greater functional disability correlated with higher tCho levels. Conclusion: Hippocampal 1H-MRS may not only contribute to a better academic understanding of extra-motor disease burden in ALS, but given its sensitive correlations with validated clinical metrics, it may serve as practical biomarker for future clinical and clinical trial applications. Neuroimaging protocols in ALS should incorporate MRS in addition to standard structural, functional, and diffusion sequences