Charcot-Marie-Tooth disease type 2 and P0 gene mutations.
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Adult↗
Biomedical subjects
A Sghirlanzoni
Publications and source records attributed to A Sghirlanzoni.
Detection of hereditary neuropathy with liability to pressure palsies among patients with acute painless mononeuropathy or plexopathy.
Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant disorder characterized by recurrent mononeuropathies or brachial plexopathies, commonly associated with a chromosome 17p11.2-12 deletion encompassing the peripheral myelin protein-22 (PMP22) gene. We tried to identify criteria distinguishing HNPP among patients with acute painless mononeuropathy/plexopathy. We investigated by pulsed-field gel electrophoresis the presence of the deletion in 27 patients with isolated or recurrent acute painless mononeuropathy or brachial plexopathy, and no obvious cause of neuropathy. Eight patients carried the deletion, whereas 19 had neither the deletion nor mutations in the PMP22 gene. Age at onset, presenting modality, precipitating events, and rate of recovery did not significantly differ in the two groups. Family history was informative for HNPP diagnosis in 3 cases only. HNPP patients more often showed recurrent episodes, brachial plexopathy, and clinical or electrophysiologic involvement of other nerves. Non-HNPP patients more frequently had peroneal palsy, recent weight loss, and normal electrophysiologic examination in other nerves. Signs of generalized neuropathy and evidence of disease in other family member are often subtle in HNPP and must be thoroughly investigated in patients with acute painless mononeuropathy/plexopathy.
Action Potentials↗
"La toccatina": polyglottal aphasia in Pirandello.
"La toccatina" [literally, "The Light Touch"] was the stroke that made Cristoforo Golisch aphasic and the title that Luigi Pirandello gave to a short story published in 1906. After having become suddenly aphasic, the protagonist of the story forgets how to speak everyday Italian but preserves the ability to express himself in German, the mother tongue that he has become so unused to speaking that it seemed he had forgotten it. The family circumstances of Pirandello certainly favoured his contacts with the neuropsychiatric environment of the time, the fruit of which is his description of an aphasic syndrome in a bilingual patient.
Aphasia↗
Neurologic complications of epidural anesthesia.
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Anesthesia, Epidural↗
Epidural anesthesia.
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Anesthesia, Epidural↗
PMP22 frameshift mutation and hereditary neuropathy with liability to pressure palsies.
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Frameshift Mutation↗
Gene dosage effects in hereditary peripheral neuropathy. Expression of peripheral myelin protein 22 in Charcot-Marie-Tooth disease type 1A and hereditary neuropathy with liability to pressure palsies nerve biopsies.
A duplication of a 1.5-Megabase genomic region encompassing the gene for the peripheral myelin protein 22 (PMP22) is found on chromosome 17p11.2-12 in Charcot-Marie-Tooth disease type 1A (CMT1A), whereas the reciprocal deletion is associated with hereditary neuropathy with liability to pressure palsies (HNPP). Since most CMT1A patients harbor three copies of the PMP22 gene, and most HNPP patients carry only a single copy, a gene dosage effect has been proposed as a mechanism for both diseases. We have analyzed the steady-state expression of PMP22 protein in sural nerve biopsies from three CMT1A and four HNPP patients. Quantitative immunohistochemical determination showed that PMP22 protein expression relative to that of myelin protein zero and myelin basic protein was increased in all CMT1A patients and reduced in all HNPP patients, as compared with biopsy samples of patients with normal PMP22 gene expression. These data demonstrate that both neuropathies result from an imbalance of PMP22 protein expression.
Adolescent↗
Phenotypic heterogeneity in hereditary neuropathy with liability to pressure palsies associated with chromosome 17p11.2-12 deletion.
Hereditary neuropathy with liability to pressure palsies (HNPP) is commonly associated with a 1.5-megabase deletion on chromosome 17p11.2-12. We analyzed the phenotypic expression of the deletion in 39 HNPP patients from 16 families carrying the deletion. Two-thirds of the individuals had episodes of acute mononeuropathy, often involving nerve territories of the upper limbs or brachial plexus; however, 41% of affected subjects were unaware of their disease, and 25% were almost or totally free of symptoms; one-third complained of chronic symptoms and four older patients had a picture of polyneuropathy. Electrophysiologic abnormalities differed among affected subjects, ranging from conduction abnormalities localized at common entrapment sites to diffuse conduction slowing, usually more evident at entrapment sites; patients from one family had preeminent proximal involvement. The spectrum of phenotypic expression of deletion-associated HNPP appears to be broader than previously thought. The prevalence of the disease is probably underestimated, and the availability of molecular diagnosis should increase disease detection.
Adolescent↗
Kennedy's disease: clinical and molecular study of two Italian families.
Kennedy's disease, or spinal and bulbar muscular atrophy (SBMA), is a rare X-linked motoneuron disorder with variable signs of androgen insensitivity. It is associated with the expansion of a trinucleotide CAG repeat within the androgen receptor (AR) gene. We here report our clinical and molecular findings in two Italian families with Kennedy's disease. The increased size of the CAG repeat was demonstrated in four affected males and seven carrier females.
Aged↗
Spinal epidural abscess complicating tuberculous spondylitis.
We report the case of a patient with tuberculous L1-L2 spondylo-discitis complicated by a spinal epidural abscess which extended anteriorly to the cord up to the low cervical level. Mild signs and symptoms of spinal cord involvement improved with antituberculous therapy; however, after seven months of therapy, the MRI appearance of the abscess findings was unchanged. An attempt at surgical decompression and drainage of the abscess was unsuccessful because of the presence of dense scar tissue.
Abscess↗
The last days of Alessandro Manzoni.
Alessandro Manzoni died on 22 May 1873 at the age of 88. On the morning of 6 January 1873, on his way to Mass in the Milanese church of San Fedele, he fell and hit his head on the church steps. From the newspaper accounts of the day, it appears that this apparently banal accident was fatal for the old writer. It seems likely that his death was caused by a chronic subdural hematoma.
Famous Persons↗
Unrecognized Charcot-Marie-Tooth disease: diagnostic difficulties in the assessment of recovery from paralysis.
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Adolescent↗
A 1.5-Mb deletion in 17p11.2-p12 is frequently observed in Italian families with hereditary neuropathy with liability to pressure palsies.
Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant disorder characterized by recurrent mononeuropathies. A 1.5-Mb deletion in chromosome 17p11.2-p12 has been associated with HNPP. Duplication of the same 1.5-Mb region is known to be associated with Charcot-Marie-Tooth disease type 1 (CMT1A), a more severe peripheral neuropathy characterized by symmetrically slowed nerve conduction velocity (NCV). The CMT1A duplication and HNPP deletion appear to be the reciprocal products of a recombination event involving a repeat element (CMT1A-REP) that flanks the 1.5-Mb region involved in the duplication/deletion. Patients from nine unrelated Italian families who were diagnosed with HNPP on the basis of clinical, electrophysiological, and histological evaluations were analyzed by molecular methods for DNA deletion on chromosome 17p. In all nine families, Southern analysis using a CMT1A-REP probe detected a reduced hybridization signal of a 6.0-kb EcoRI fragment mapping within the distal CMT1A-REP, indicating deletion of one copy of CMT1A-REP in these HNPP patients. Families were also typed with a polymorphic (CA)n repeat and with RFLPs corresponding to loci D17S122, D17S125, and D17S61, which all map within the deleted region. Lack of allelic transmission from affected parent to affected offspring was observed in four informative families, providing an independent indication for deletion. Furthermore, pulsed-field gel electrophoresis analysis of SacII-digested genomic DNA detected junction fragments specific to the 1.5-Mb HNPP deletion in seven of nine Italian families included in this study. These findings suggest that a 1.5-Mb deletion on 17p11.2-p12 is the most common mutation associated with HNPP.
Charcot-Marie-Tooth Disease↗
Acoustic nerve in peripheral neuropathy: a BAEP study. Brainstem Auditory Evoked Potentials.
We performed BAEP study to evaluate acoustic nerve involvement in 102 patients affected by peripheral neuropathies of different etiology, predominantly hereditary and inflammatory acquired neuropathies. Prolonged latency of early waves, indicative of slowing in VIII nerve conduction, was found in a high percentage of cases. Abnormalities were far more frequent (44% vs 14%) and severe in patients with demyelinating rather than axonal neuropathy. Among demyelinating neuropathy, the most severe latency delay was found in Hereditary Motor and Sensory Neuropathy type III. The pattern of acoustic nerve involvement differed slightly between Hereditary Motor and Sensory Neuropathy type I and acquired inflammatory demyelinating polyradiculoneuropathy, perhaps reflecting different pathogenetic mechanisms and different sites of VIII nerve demyelination.
Adolescent↗
The POEMS syndrome: report of six cases.
We report six patients affected by POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy, and Skin changes), a peculiar multiorgan disease frequently associated with osteosclerotic myeloma or other plasma cell disorders. Sensorimotor polyneuropathy was associated with multisystem involvement in all of the patients, with osteosclerotic myeloma in 2 cases, monoclonal gammopathy of undetermined significance in 2 cases and Castleman's disease in the final two. In all of the patients, sural nerve biopsy findings were consistent with a mixed, axonal and demyelinating neuropathy. Increased levels of Interleukin-6 were found in two cases, but the pathogenesis of the disease is far from established.
Aged↗
Homozygous hypertrophic hereditary motor and sensory neuropathies.
We compared 25 autosomal dominant hereditary motor and sensory neuropathy (HMSN) type I patients with 7 subjects affected by hypertrophic HMSN with non-dominant inheritance. All the autosomal dominant HMSN I cases carried the chromosome 17p11.2 duplication, providing evidence that it is widely represented in HMSN I families. The second group included: two siblings born to unrelated, unaffected parents and suffering from hypertrophic HMSN of strikingly different severity; two sisters with HMSN I phenotype, born to first-cousin unaffected parents; two brothers with HMSN III phenotype born to unrelated parents both showing HMSN II phenotype; a child with classic HMSN III phenotype, born to unrelated, unaffected parents. The 17p11.2 duplication was not found in any of the patients of the second series or in their parents. Our data provide further evidence that: HMSN III is heterogeneous and encompasses the homozygous expressions of different neuropathic genes; it is advisable to separate autosomal recessive hypertrophic HMSN from dominant HMSN Ia, because they appear to be due to different DNA mutations.
Adolescent↗
Neurologic symptoms after epidural anaesthesia. Report of three cases.
We describe 3 patients, who exhibited neurological symptoms after single dose epidural anaesthesia. In patient 1 an unrecognized spinal arteriovenous fistula (AVF) caused paraparesis following epidural block. The dilated veins draining an AVF are space-occupying structures and the injection of the anaesthetic solution may have precipitated latent ischaemic hypoxia of the spinal cord due to raised venous pressure. In patient 2, epidural block was followed by postoperative permanent saddle pain and hypoaesthesia. The injection of the anaesthetic in a narrow spinal canal with multiple discal protrusions and restriction of interlaminar foramina may have acutely produced mechanical compression of the spinal cord or roots. Patient 3 exhibited post-epidural block spinal arachnoiditis. Although the few reported cases of this syndrome exhibit severe neurological damage, our patient presented with scarse symptoms. Our cases point out the importance of accurate neurological history and examination of candidates for epidural anaesthesia and of accurate anaesthetic history for neurological patients.
Adult↗
17p11.2 duplication is a common finding in sporadic cases of Charcot-Marie-Tooth type 1.
We investigated the presence of duplication in chromosome 17p11.2 in 4 individuals with sporadic Charcot-Marie-Tooth disease (CMT 1) and 1 isolated case where a definite differential diagnosis between CMT 1 and Déjérine-Sottas disease was not achieved. The 5 affected cases and their parents and relatives were submitted to a complete clinical, neurophysiologic and genetic evaluation. A sural nerve biopsy was performed in all the isolated patients. Paternity was tested and confirmed. The presence of DNA duplication was detected in all the sporadic cases and was absent in all parents and relatives, thus confirming that a de novo dominant mutation is commonly present also in patients without a familial history and that there is a practical relevance of the genetic study in distinguishing isolated cases of CMT 1 from other forms of hereditary motor and sensory neuropathies or demyelinating neuropathies.
Adolescent↗