Motor nerve biopsy: clinical usefulness and histopathological criteria.

Early differential diagnosis of motor neuropathies (MN) and lower motor neuron diseases (LMND) is important, as prognosis and therapeutic approaches are different. We evaluated the diagnostic contribution of the biopsy of the motor branch of the obturator nerve and gracilis muscle in 21 consecutive patients in which, after proper clinical and neurophysiological studies, the differential diagnosis was still open. At baseline, motor biopsy was performed; diagnostic confirmation was obtained by 2-year clinical follow-up. Our results support the usefulness of this diagnostic procedure for selected cases of MN and LMND.

Auditory event-related potentials in non-demented patients with sporadic amyotrophic lateral sclerosis.

OBJECTIVE: To investigate the presence of sub-clinical cognitive dysfunction in non-demented patients with amyotrophic lateral sclerosis (ALS) using auditory event-related potentials (ERPs). METHODS: Ten subjects with ALS and 10 age- and sex-matched controls performed a passive three-stimulus paradigm with standard (80%), deviant (16%) and distracter (4%) stimuli. To quantify the mismatch component, the evoked response to the standard tones was subtracted from the corresponding deviant stimuli and novel response; the P3a component was obtained by subtracting the response to the standard tone from that to the novel stimuli. The amplitude and latency for the N1 component obtained with the standard stimuli were also measured. Clinical features, disability, cognitive status and depression were evaluated with standardised scales. RESULTS: There were no significant differences between patients and controls for latencies, while the N1, P3a and MMN (obtained by the subtraction Novel-Standard) were of lower amplitude in patients than in controls. In the patient group, the P3a latency correlated with months from disease onset and symptoms severity, measured with the amyotrophic lateral sclerosis severity scale. CONCLUSIONS: Our findings confirm the hypothesis of a sub-clinical cognitive impairment in non-demented ALS patients, suggesting pathological involvement beyond the motor areas. SIGNIFICANCE: ERPs seem to be a promising technique to detect the possible impairment of extra-motor sub-clinical dysfunction in ALS, and an appropriate technique for the cognitive follow-up, as passive tasks, not requiring motor responses, are particularly adequate in a disorder leading to severe loss of motor function.

Differential expression of ceruloplasmin isoforms in the cerebrospinal fluid of amyotrophic lateral sclerosis patients.

Amyotrophic lateral sclerosis (ALS) a fatal degenerative disease that selectively affects motor neurons, likely results from a complex interplay among oxidative injury, excitotoxic stimulation, protein aggregation and genetic factors. Ceruloplasmin (Cp) protein is a ferroxidase that oxidizes toxic ferrous iron to its nontoxic ferric form, protecting the central nervous system (CNS) from iron deposition. Cp is thus considered as one of the main systems dedicated to the protection of the CNS from oxidative stress damage. We investigated Cp protein behaviour in the cerebrospinal fluid (CSF) of ALS patients of recent onset. An increased expression of Cp was observed in ALS (n = 16) compared to two control groups (healthy subjects, n = 11 and peripheral neuropathy patients, n = 10). 2-DE analysis revealed a differential expression of Cp isoforms in ALS patients compared to controls. ALS samples showed an increase in the relative abundance of more basic Cp forms, corresponding to the nonsialylated proteins. Despite the increase in protein expression, ferroxidase activity evaluated in the CSF of ALS patients was comparable to that of the controls, indicating a Cp functional impairment. Ceruloplasmin isoforms profile may be proposed as disease feature that could provide insight into the molecular mechanisms of ALS pathogenesis.

Pigment epithelium-derived factor is differentially expressed in peripheral neuropathies.

Peripheral neuropathies are characterized by asymmetrical slowly progressive weakness with no upper motor neuron signs, and can occur either with or without pain. Due to poor knowledge of the disease mechanisms, available pain treatment is very limited. Because of the difficulties and invasiveness involved when performing direct analysis on peripheral and CNS, pathological markers can be searched for in the cerebrospinal fluid (CSF) as an alternative. To investigate pain mechanisms in peripheral neuropathy and find diagnostic markers, CSF samples were analyzed by a differential expression proteomic approach. We studied CSF from: neuropathic patients with pain (PN), without pain (NPN) and healthy controls (CN). 2-DE analysis showed ten protein spots differentially expressed, and six of these were identified by MS. In NPN patients we found an expression level decrease of three pigment epithelium-derived factor (PEDF) protein isoforms. Immunoblot with a specific antibody revealed the presence of additional PEDF isoforms not highlighted by differential expression analysis. Fucose residues on the oligosaccharide chain were found only in the isoforms down regulated in NPN patients. Considered as PEDF has important neurobiological effects, it might be considered an interesting pathology marker.

Case of symptomatic propriospinal myoclonus evolving toward acute "myoclonic status".

Propriospinal myoclonus is a rare motor disorder consisting of involuntary spinal-generated muscular jerks. Here, we report a severe and uncommon case of propriospinal myoclonus that appeared after a vertebral fracture of T11. In this patient, the polysomnographic investigation showed continuing focal myoclonic activity in axial muscles during stable sleep and an acute progression into a myoclonic "status" associated with respiratory failure and loss of consciousness. It is necessary to consider this severe progression and support it with prompt emergency maneuvers and adequate pharmacotherapy.