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Charcot‐Marie‐Tooth 1A (CMT1A) neuropathy is caused by duplication of the peripheral myelin protein 22(PMP22) gene, leading to protein overexpression. Although this protein has a role in regulating Schwann cell growth and peripheral myelin compaction, how altered concentrations of PMP22 impair myelination is unknown. We established dorsal root ganglia (DRG) cultures from a transgenic rat overexpressing PMP22 (PMP22tg) to study the behavior of PMP22tgSchwann cells in early stages of development and myelination. We used reverse transcriptase–polymerase chain reaction and light and electron microscopy to study PMP22 expression and myelin formation. Myelin ultrastructure was evaluated in sural nerves from CMT1A patients to compare experimental and human findings. PMP22tgDRG cultures contained a greater number of internodes devoid of myelin, in the absence of remyelination, and increased periodicity of myelin lamellae compared with normal cultures. Widening of myelin lamellae was also observed in CMT1A biopsy specimens. Our results suggest that both functions of PMP22, in regulating Schwann cell differentiation and contributing to peripheral myelin compaction, are affected by its overexpression. The presence of similar myelin abnormalities in PMP22tgcultures and human nerves emphasizes the importance of developing in vitro models of hereditary neuropathies to study their underlying pathomechanisms.

We studied the expression of insulin‐like growth factor I (IGF‐I) and its receptor in sural nerves from 8 diabetic patients divided into insulin‐treated (IT) and non–insulin‐treated (NIT) groups, compared with 5 patients with axonal neuropathies and 4 control patients (undergoing biopsies for diagnostic purposes). Insulin‐like growth factor I mRNA levels did not differ in diabetic cases compared with control subjects. In sural nerves from IT patients and axonal neuropathies, IGF‐I expression was higher than in NIT subjects and diagnostic controls. Changes in IGF‐I receptor mRNA levels paralleled those of the ligand. Insulin‐like growth factor I immunoreactivity was higher in nerves undergoing axonal degeneration and higher in IT than NIT diabetic patients and diagnostic controls. These findings suggest that insulin treatment increases IGF‐I expression in diabetic nerves. Our data do not support the hypothesis of an absolute IGF‐I deficiency in human diabetic neuropathy. A Schwann cell's incapacity to increase IGF‐I expression after severe nerve damage, as happens in axonal neuropathies, may be a cofactor in the pathogenesis of diabetic neuropathy. © 2001 John Wiley & Sons, Inc. Muscle Nerve 24: 622–629, 2001.

Concurrent recordings of (i) the soleus H reflex and (ii) the underlying afferent (P1) and efferent (P2) neural volleys were performed during a protracted, moderate, isometric, voluntary contraction of the soleus (S) muscle, and the subsequent release period. Besides the expected enhancement of the H reflex, muscular contraction caused a significant reduction in the corresponding central delay (as extrapolated from variations of P1–P2interval), while the opposite trend occurred during the release phase. Control experiments, based on (a) neural blockade below the stimulation site, (b) muscle stretching at the end of the muscular contraction, (c) changes in amplitude of homonymous and heteronymous S responses, and (d) variations in effectiveness of homonymous and heteronymous conditioning volleys on the S motoneuronal pool, showed that both voluntary contraction and the subsequent release period are associated with a reduced effectiveness of Ia afferents, while postsynaptic motoneuronal responsiveness is significantly modified only during the actual contraction time. © 1998 John Wiley & Sons, Inc. Muscle Nerve 21:439–453, 1998.

Hereditary neuropathy with a liability to pressure palsies (HNPP) is an autosomal dominant disorder characterized by recurrent pressure palsies generally precipitated by minor trauma; weakness and paraesthesia usually improve and recover completely in a few months. By Southern blotting and fluorescent in situ hybridization analysis we confirm the presence of a 17p11.2 deletion in familial and in isolated cases of HNPP, suggesting that molecular analysis of the 17p11.2 region could also be a reliable and non-invasive method of diagnosis in sporadic cases, where a correct diagnosis usually requires a nerve biopsy. Although HNPP is a mild disease and not all patients seek medical attention, a presymptomatic diagnosis is useful for assessing the risk during genetic counselling, due to the inheritance of the mutation.

F-wave responses from abductor pollicis brevis muscle occurred more frequently, with a larger amplitude and longer duration in rigid parkinsonian patients than in age-matched normal controls. F-wave potentiation during voluntary contraction was impaired in parkinsonian patients. These findings suggest that spinal motor neuron excitability is enhanced in rigidity. F-wave amplitude was significantly correlated to the clinical evaluation of motor disability, so that the F wave may be regarded as a useful approach to quantitative evaluation of rigidity.

Concurrent recordings of (i) the soleus H reflex and (ii) the underlying afferent (P1) and efferent (P2) neural volleys were performed during a protracted, moderate, isometric, voluntary contraction of the soleus (S) muscle, and the subsequent release period. Besides the expected enhancement of the H reflex, muscular contraction caused a significant reduction in the corresponding central delay (as extrapolated from variations of P1–P2 interval), while the opposite trend occurred during the release phase. Control experiments, based on (a) neural blockade below the stimulation site, (b) muscle stretching at the end of the muscular contraction, (c) changes in amplitude of homonymous and heteronymous S responses, and (d) variations in effectiveness of homonymous and heteronymous conditioning volleys on the S motoneuronal pool, showed that both voluntary contraction and the subsequent release period are associated with a reduced effectiveness of Ia afferents, while postsynaptic motoneuronal responsiveness is significantly modified only during the actual contraction time. © 1998 John Wiley & Sons, Inc. Muscle Nerve 21:439–453, 1998.

Hereditary neuropathy with liability to pressure palsies (HNPP) is associated with a deletion in chromosome 17p 11.2, which includes the gene for the peripheral myelin protein 22 (PMP‐22). A “gene dosage” effect is probably the mechanism underlying HNPP, but the amount of PMP‐22 mRNA in sural nerves of HNPP patients is highly variable and the role of PMP‐22 underexpression in impairing myelination has yet to be clarified. We have studied 6 genetically proven HNPP patients, to evaluate the relationship between PMP‐22 mRNA levels, and clinical, neurophysiological, and neuropathological findings. Underexpression of PMP‐22 mRNA correlates with disease severity and with mean axon diameter and g ratio, but not with myelin thickness, number of “tomacula,” or nerve conduction parameters. Our findings further confirm that underexpression of PMP‐22 is the main pathogenetic mechanism underlying the severity of clinical symptoms and signs in HNPP. Smaller axons in sural nerves of HNPP patients with lower PMP‐22 levels suggests that underexpression of PMP‐22 may also affect axon development.

To the Editor.—In the recent article by Dubin et al (1983;249:60) on the differentiation in the emergency department of organic brain syndrome from functional psychiatric illness (ie, organic v functional acute psychosis), the authors do not mention the EEG, a rapid and inexpensive investigation. Pro and Wells,1 in a review on the EEG and delirium, concluded that, in their opinion, the EEG is a useful and often ancillary procedure in the differential diagnosis of delirium, but they complain about the lack of evidence to "label EEG a luxury or a necessity" in the diagnosis of psychotic patients.In a study of 114 patients consecutively referred to us with acute or subacute confusional state, we were able to find normal EEG recordings in 15 of 18 patients (83%) with psychiatric illness and only in eight of 96 patients (8%) with acute confusional state from organic, intracranial, or extracranial disorders

We investigated the contribution of Schwann cell-derived ciliary neurotrophic factor (CNTF) to the pathogenesis of Charcot-Marie-Tooth disease type 1A (CMT1A) and addressed the question as to whether it plays a role in the development of axonal damage observed in the disease, with aging. Ciliary neurotrophic factor was underexpressed in experimental CMT1A but not in other models of hereditary neuropathies. Sciatic nerve crush experiments and dosage of CNTF at different time points showed that expression of this trophic factor remained significantly lower in CMT1A rats than in normal controls; moreover, in uninjured CMT1A sciatic nerves CNTF levels further decreased with ageing, thus paralleling the molecular signs of axonal impairment, that is increased expression of non-phosphorylated neurofilaments and amyloid precursor protein. Administration of CNTF to dorsal root ganglia cultures reduced dephosphorylation of neurofilaments in CMT1A cultures, without improving demyelination. Taken together, these results provide further evidence that the production of CNTF by Schwann cells is markedly reduced in CMT1A. Moreover, the observations suggest that trophic support to the axon is impaired in CMT1A and that further studies on the therapeutic use of trophic factors or their derivatives in experimental and human CMT1A are warranted.