Mauro Lo Monaco

Multiperspective assessment of carpal tunnel syndrome A multicenter study

Objective: To assess the clinical and neurophysiologic dissociation often observed in clinical practice, and to improve patient evaluation for diagnosis of carpal tunnel syndrome (CTS). Methods: The Italian CTS Study Group studied 1,123 idiopathic CTS hands with multiple measurements—clinical, neurophysiologic, and patient-oriented—of CTS. Results: Clinical and neurophysiologic relationships were very strong when the clinical picture was evaluated by the hand functional measurements, with an exponential increase in functional impairment as the classification of neurophysiologic severity progressed. Conversely, symptoms and pain did not increase as the classification of neurophysiologic severity progressed: 1) A large part of the CTS population complained of severe symptoms, although minimal functional impairment and minimal or no electrophysiologic abnormalities were observed; and 2) symptoms improved in the patients with more severe neurophysiologic and clinical examination scenarios. Conclusions: Multiperspective and multimeasurement assessment, even when using a validated patient-oriented tool, provided interesting information that confirmed and clarified the clinical neurophysiologic dissociation often observed in carpal tunnel syndrome (CTS) patients. Furthermore, CTS appeared to be an ideal model for evaluating the importance of patient-oriented measurement.

A useful electrophysiologic parameter for diagnosis of carpal tunnel syndrome

In 43 patients (50 hands) with clinical manifestations of mild‐moderate carpal tunnel syndrome (CTS) and 36 healthy volunteers (40 hands), orthodromic sensory nerve conduction velocity (SNCV) was measured with surface electrodes in the median nerve between the third digit and palm and between the palm and wrist. These figures were used to calculate the ratio of distal to proximal conduction (distoproximal ratio). All 90 hands were also subjected to other nerve conduction studies used for diagnosis of CTS. All control hands presented distoproximal ratios <1.0, reflecting higher conduction rates in the proximal segment. In contrast, 49 of 50 CTS hands (98%) presented reversed ratios (>1.0) indicating compromised proximal conduction. The sensitivity of this test was significantly greater than that of other methods evaluated, including comparative studies and segmental study of the palm‐wrist portion of the median nerve. Segmental study of median SNCV with calculation of the distoproximal ratio is a sensitive technique for diagnosis of CTS in patients with normal findings in standard nerve conduction studies.

Carpal tunnel syndrome : Indication for surgical treatment based on electrophysiologic study

A prospective study of 50 hands from 45 consecutive patients surgically treated for idiopathic carpal tunnel syndrome was conducted to determinate the recovery capacity of the median nerve after open surgical release. Subjects were evaluated by clinical history, physical examination, and electrophysiologic testing. Motor and sensory terminal latencies and motor and sensory conduction velocities were examined before surgery and 2 weeks, 2 months, and 6 months after surgical decompression. All patients showed improvement of postoperative electrophysiologic values; the amount of improvement was dependent on the degree of preoperative impairment. Complete restoration of clinical and electrophysiologic nerve function was observed only in patients with mild carpal tunnel syndrome.

Long-Term Results of Corticosteroid Therapy in Patients with Myasthenia Gravis

We studied the long-term outcome of prednisone therapy in 104 patients with myasthenia gravis (MG). At the end of the follow-up period, good therapeutic results were recorded in 85 patients (81.7%), poor results in 13 (12.5%) and no significant change of MG status in 6 (5.8%). We found a correlation between the duration of treatment and the incidence of steroid side effects. The presence of thymoma and severe forms of MG were associated with relapsing disease requiring prolonged corticosteroid regimens. The age at the start of therapy did not influence significantly the response to treatment.

Accuracy of reinnervation by peripheral nerve axons regenerating across a 10-mm gap within an impermeable chamber.

The axon regeneration following a peripheral nerve injury often fails to restore a complete functional recovery. One of the causes of this unsatisfactory result has been attributed to regrowth of regenerating fibers to inappropriate peripheral targets. The accuracy of reinnervation by axons regenerating across a 10-mm gap within an impermeable chamber has been studied by using a sequential retrograde double-labeling technique. Despite the long gap between the nerve stumps, at 4 weeks a mean of 30.5% of the regenerating axons can reinnervate the original muscular area. These data confirm previous studies in which a preferential reinnervation is reported not to be absolutely dependent on the axons mechanical alignment.

Neurophysiological assessment in the diagnosis of botulism: usefulness of single-fiber EMG.

We report the clinical, serological, and neurophysiological findings in seven patients with foodborne botulism caused by ingestion of black olives in water. The clinical picture was characterized by mild symptoms with a long latency of onset and by involvement of cranial and upper limb muscles; only one patient, a child, developed respiratory failure. Spores of Clostridium botulinum were found in stools in some but not all cases. Conventional neurophysiological tests had low sensitivity; abnormal findings were present only in the patient with severe clinical involvement, in whom compound muscle action potentials (CMAPs) appeared reduced. Repetitive nerve stimulation at a high rate showed pseudofacilitation and not true posttetanic facilitation, but single‐fiber electromyography (SFEMG) showed abnormalities of neuromuscular transmission in every case. Neurophysiological evaluation, particularly SFEMG, is important because it allows rapid identification of abnormal neuromuscular transmission while bioassay studies are in progress.

Uncovering amyotrophic lateral sclerosis phenotypes: clinical features and long-term follow-up of upper motor neuron-dominant ALS

Abstract The aim of our study was to analyse the natural history and clinical features of upper motor neuron- dominant (UMN-D) ALS. We studied a large series of sporadic ALS patients admitted in a single referral centre over a 23-year period. UMN-D phenotype was compared with other ALS forms, including classic ALS, flail arm and progressive muscular atrophy. Seven hundred and thirty-four sporadic ALS patients were included of which 163 had UMN-D ALS. The mean age of onset in UMN-D ALS (52 years) was 10 years lower than in classic ALS (61.4 years, p < 0.0001); sex ratio by age groups significantly differed with respect to other phenotypes. The pattern of spread of lower motor neuron signs in UMN-D was characterized by early involvement of upper limb muscles and late impairment of respiratory muscles. Duration of the disease was longer in the UMN-D group (56 months) than in classic ALS (33 months, p < 0.001). The UMN-D phenotype was a strong independent predictor of long survival. In summary, UMN-D ALS showed significant differences in age of onset, sex ratio, pattern of spreading and prognosis with respect to other ALS forms, most probably reflecting biological differences.

Rippling muscle disease and cardiomyopathy associated with a mutation in the CAV3 gene

Caveolin-3, the myocyte-specific isoform of caveolins, is preferentially expressed in skeletal, cardiac and smooth muscles. Mutations in the CAV3 gene cause clinically heterogeneous neuromuscular disorders, including rippling muscle disease, or cardiopathies. The same mutation may lead to different phenotypes, but cardiac and muscle involvement rarely coexists suggesting that the molecular network acting with caveolin-3 in skeletal muscle and heart may differ. Here we describe an Italian family (a father and his two sons) with clinical and neurophysiological features of rippling muscle disease and heart involvement characterized by atrio-ventricular conduction defects and dilated cardiomyopathy. Muscle biopsy showed loss of caveolin-3 immunosignal. Molecular studies identified the p.A46V mutation in CAV3 previously reported in a German family with autosomal dominant rippling muscle disease and sudden death in few individuals. We suggest that cardiac dysfunction in myopathic patients with CAV3 mutations may be underestimated and recommend a more thorough evaluation for the presence of cardiomyopathy and potentially lethal arrhythmias.

Modality-related scalp responses after electrical stimulation of cutaneous and muscular upper limb afferents in humans

To elucidate whether the selective electrical stimulation of muscle as well as cutaneous afferents evokes modality‐specific responses in somatosensory evoked potentials (SEPs) recorded on the scalp of humans, we compared scalp SEPs to electrical stimuli applied to the median nerve and to the abductor pollicis brevis (APB) motor point. In three subjects, we also recorded SEPs after stimulation of the distal phalanx of the thumb, which selectively involved cutaneous afferents. Motor point and median nerve SEPs showed the same scalp distribution; moreover, very similar dipole models, showing the same dipolar time courses, explained well the SEPs after both types of stimulation. Since the non‐natural stimulation of muscle afferents evokes responses also in areas specifically devoted to cutaneous input processing, it is conceivable that, in physiological conditions, muscle afferents are differentially gated in somatosensory cortex. The frontocentral N30 response was absent after purely cutaneous stimulation; by contrast, it was relatively more represented in motor point rather than in mixed nerve SEPs. These data suggest that the N30 response is specifically evoked by proprioceptive inputs.

TTR-related amyloid neuropathy: clinical, electrophysiological and pathological findings in 15 unrelated patients

Familial amyloid polyneuropathy (FAP) is a rare condition caused by mutations of the transthyretin (TTR) gene and it is generally characterized by a length-dependent polyneuropathy affecting prevalently the small fibers. We reviewed clinical, electrophysiological and pathological findings of 15 unrelated patients with genetically confirmed TTR-FAP. All patients presented a progressive sensory-motor polyneuropathy. Pathological findings were negative for amyloid deposits in about half of the cases. Sequence analysis of TTR gene revealed the presence of three different mutations (p.Val30Met, p.Phe64Leu, and p.Ala120Ser). The p.Val30Met was the most frequently identified mutation and it often occurred in apparently sporadic cases. Conversely, the p.Phe64Leu generally presented in a high percentage of familial cases in patients coming from Southern Italy. Clinicians should consider, to avoid misdiagnosis, the screening for TTR mutations in patients presenting with progressive axonal polyneuropathy of undetermined etiology, including apparently sporadic cases with pathological examinations negative for amyloid deposition.