Mapping cortical degeneration in ALS with magnetization transfer ratio and voxel-based morphometry.

Pathological and imaging data indicate that amyotrophic lateral sclerosis (ALS) is a multisystem disease involving several cerebral cortical areas. Advanced quantitative magnetic resonance imaging (MRI) techniques enable to explore in vivo the volume and microstructure of the cerebral cortex in ALS. We studied with a combined voxel-based morphometry (VBM) and magnetization transfer (MT) imaging approach the capability of MRI to identify the cortical areas affected by neurodegeneration in ALS patients.

Structural and functional evaluation of cortical motor areas in Amyotrophic Lateral Sclerosis.

The structural and functional data gathered with Magnetic Resonance Imaging (MRI) techniques about the brain cortical motor damage in Amyotrophic Lateral Sclerosis (ALS) are controversial. In fact some structural MRI studies showed foci of gray matter (GM) atrophy in the precentral gyrus, even in the early stage, while others did not. Most functional MRI (fMRI) studies in ALS reported hyperactivation of extra-primary motor cortices, while contradictory results were obtained on the activation of the primary motor cortex.

Nerve and muscle involvement in mitochondrial disorders: an electrophysiological study.

Involvement of the peripheral nervous system in mitochondrial disorders (MD) has been previously reported. However, the exact prevalence of peripheral neuropathy and/or myopathy in MD is still unclear. In order to evaluate the prevalence of neuropathy and myopathy in MD, we performed sensory and motor nerve conduction studies (NCS) and concentric needle electromyography (EMG) in 44 unselected MD patients.

Strategies for clinical approach to neurodegeneration in Amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive and ultimately fatal neurodegenerative disorder of unknown aetiology that involves the loss of upper and lower motor neurons in the cerebral cortex, brainstem and spinal cord. Significant progress in understanding the cellular mechanisms of motor neuron degeneration in ALS has not been matched with the development of therapeutic strategies to prevent disease progression, and riluzole remains the only available therapy, with only marginal effects on disease survival. More recently alterations of mRNA processing in genetically defined forms of ALS, as those related to TDP-43 and FUS-TLS gene mutations have provided important insights into the molecular networks implicated in the disease pathogenesis.

Evaluation of corticospinal tract impairment in the brain of patients with amyotrophic lateral sclerosis by using diffusion tensor imaging acquisition schemes with different numbers of diffusion-weighting directions.

Amyotrophic lateral sclerosis is characterized by degeneration of upper and lower motor neurons. Diffusion tensor imaging (DTI) indexes obtained along the corticospinal tracts distinguish ALS patients and control subjects. Diffusion tensor imaging can be estimated from at least 6 diffusion-weighted images; however an acquisition scheme with a higher number of diffusion directions allows a more robust estimation of DTI indexes.

A new truncating MPZ mutation associated with a very mild CMT1 B phenotype.

We have investigated a 34-year-old female who had mild clinical and electrophysiological features of demyelinating peripheral neuropathy. She presented a novel frameshift mutation (V160fsX3) in the exon 4 of the Myelin Protein Zero (MPZ) gene. Clinical and genetic studies performed on her family revealed the same mutation in her oligosymptomatic mother and sister.

D90A-SOD1 mutation in ALS: The first report of heterozygous Italian patients and unusual findings.

Among the 140 Cu/Zn superoxide dismutase-1 (SOD1) gene mutations associated with ALS, only D90A, the most prevalent mutation in Europe, has been clearly shown to cause recessive and dominant ALS. Here we first describe two, apparently sporadic, Italian ALS patients heterozygous for the D90A mutation. One patient experienced early sensory involvement, confirmed by nerve biopsy.

The first Italian family with evidence of pyramidal impairment as phenotypic manifestation of Silver syndrome BSCL2 gene mutation.

Silver syndrome (SPG17) is a rare form of hereditary spastic paraparesis. Its relationship to distal hereditary motor neuropathy (dHMN) type V is underlined by the recent discovery of causative mutation in BSCL2 gene coding for a protein termed seipin, an integral membrane protein of endoplasmic reticulum, with unknown function. Here we report the third Italian family with dHMN and SPG17 in which two affected members harbor the heterozygous N88S mutation in the BSCL2 gene.

Lack of association between the APEX1 Asp148Glu polymorphism and sporadic amyotrophic lateral sclerosis.

Impairments in DNA repair enzymes have been observed in amyotrophic lateral sclerosis (ALS) tissues, particularly in the activity of the apurinic/apyrimidinic endonuclease 1 (APEX1). Moreover, it was suggested that the common APEX1 Asp148Glu polymorphism might be associated with ALS risk. To further address this question we performed the present study aimed at evaluating the contribution of the APEX1 Asp148Glu polymorphism in sporadic ALS (sALS) risk and clinical presentation, including age and site of onset and disease progression.

Association of the hOGG1 Ser326Cys polymorphism with sporadic amyotrophic lateral sclerosis.

Amyotropic lateral sclerosis (ALS) is a fatal and progressive neurodegenerative disease causing the loss of motoneurons of the brain and the spinal cord. The etiology of ALS is still uncertain, but males are at increased risk for the disease than females. Several studies have suggested that motoneurons in ALS might be subjected to the double insult of increased DNA oxidative damage and deficiencies in DNA repair systems.

Functional diagnostics in mitochondrial diseases.

Mitochondrial diseases (MD) with respiratory chain defects are caused by genetic mutations that determine an impairment of the electron transport chain functioning. Diagnosis often requires a complex approach with measurements of serum lactate, magnetic resonance spectroscopy (MRS), muscle histology and ultrastructure, enzymology, genetic analysis, and exercise testing. The ubiquitous distribution of the mitochondria in the human body explains the multiple organ involvement.